WO1997015285A1 - Non-polymeric sustained release delivery system - Google Patents
Non-polymeric sustained release delivery system Download PDFInfo
- Publication number
- WO1997015285A1 WO1997015285A1 PCT/US1996/017082 US9617082W WO9715285A1 WO 1997015285 A1 WO1997015285 A1 WO 1997015285A1 US 9617082 W US9617082 W US 9617082W WO 9715285 A1 WO9715285 A1 WO 9715285A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- composition
- implant
- ofthe
- solvent
- tissue
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- Polymeric materials have been used for many years for producing medical devices such as sutures, surgical clips, catheters, vascular grafts, and implants.
- nonbiodegradable polymers such as polyethylene, poly(hydroxyethyl methacrylate) and ethylene-vinyl acetate copolymers have also been used for drug delivery.
- biodegradable polymers have been used in drug delivery devices because of their biodegradability. These polymers include those based upon lactide, glycolide, e-caprolactone and copolymers thereof (Yolles, U.S. Patent No. 3,887,699; Kent, U.S. Patent No. 4,675,189; Pitt, U.S. Patent No. 4,148,871; Schindler, U.S. Patent No. 4,702,917). Polyorthoesters and polyanhydrides have also been used as bioerodible matrices for drug release and as medical devices (U.S. Patent Nos. 4,093,709 and 4,138,344, Choi and Heller; U.S. Patent No. 4,906,474, Domb and
- the above-described polymers are solids at room temperature and, as a result, are shaped into solid structures outside the body and then inserted into the body by surgical procedures. If prepared as microparticles, microspheres, microcapsules or nanoparticles, such forms can be injected into the body using standard syringes and needles.
- U.S. Patent No. 4,938,763 (Dunn) describes methods and compositions in which biodegradable polymers are combined with biocompatible solvents to form a composition that can be administered into the body, whereupon the solvent diffuses or leaches away from the polymer composition into body fluids. Because the polymers are insoluble in water, they coagulate or precipitate upon contact with aqueous body fluid to form a solid implant for use as a medical device. If a drug is included in the polymer composition, it becomes incorporated into the implant matrix as the polymer coagulates. A disadvantage of such a system is that a high concentration of organic solvent may be needed to fully dissolve the polymer.
- Polymeric compositions can also have a high flow viscosity because ofthe resistance ofthe long polymer chains to movement.
- the time period of biodegradation of some polymers can only by reduced to a certain minimum because ofthe need to hydrolyze the polymer chains to short chain lengths before the polymer becomes solubilized or metabolized. Therefore, there is a need for materials that are biodegradable, and will dissolve in biocompatible solvents to form a relatively non-viscous composition, and precipitate or coagulate to form a solid implant upon exposure to water.
- Non-polymeric materials have been described for use as solid drug delivery matrices.
- Examples include cholesterol in the form of pellets for dispensing steroids (Shimkin et al., Endocrinology 29:1020 (1941)), naltrexone (Misra, "Narcotic antagonists: Naltrexone pharmochemistry and sustained release preparations," Research Monograph 28. Willette et al., eds., National Institute on Drug Abuse (1981), and a luteinizing hormone-releasing system (Kent, U.S. Patent 4,452,775).
- Phospholipids are another non-polymeric material that have been used for preparing liposomes for drug delivery.
- a disadvantage of those systems is that solid cholesterol pellets require a surgical incision or a large trochar for implantation.
- the liposomes formed from phospholipids and from cholesterol can be injected using standard syringes and needles, these materials require considerable preparation, have low stability, and only a small amount of drug can be encapsulated within the small particles and released with time.
- liposomes are small particles, they are poorly retained at the implantation site. Also, the small liposome particles are difficult to remove if complications arise and it is necessary to terminate treatment.
- an object ofthe invention is to provide a composition made of nonpolymeric material that can be used to provide a solid implant in-situ. Another object is to provide a solid implant that will provide a shorter biodegradation time than an implant formed from a biodegradable polymer. Yet another object is to provide a composition having a low flow viscosity that can be administered by a pressure applicator, and will form a solid biodegradable implant in-situ in a body for use as a medical device and/or a controlled delivery system for a drug.
- the invention is directed to a non-polymeric composition for in situ formation of a solid matrix in an animal, and use ofthe composition as a medical device or as a sustained release delivery system for a biologically-active agent, among other uses.
- the composition is composed of a biocompatible, non-polymeric material and a pharmaceutically-acceptable, organic solvent.
- the non-polymeric composition is biodegradable and/or bioerodible, and substantially insoluble in aqueous or body fluids.
- the organic solvent solubilizes the non-polymeric material, and has a solubility in water or other aqueous media ranging from miscible to dispersible.
- the non-polymeric composition When placed into an implant site in an animal, the non-polymeric composition eventually transforms into a solid structure.
- the implant can be used for treating a tissue defect by enhancing cell growth and tissue regeneration, wound and organ repair, nerve regeneration, soft and hard tissue regeneration, and the like.
- the composition can include a biologically-active agent (bioactive agent), as for example, an anti-inflammatory agent, an antiviral agent, antibacterial or antifungal agent useful for treating and preventing infections in the implant site, a growth factor, a hormone, and the like.
- bioactive agent biologically-active agent
- the resulting implant provides a system for delivering the biologically-active agent to the animal.
- the composition can also include optional ingredients such as a separate pore-forming agent for generating pores within the matrix, and/or a release rate modification agent for controlling the rate of breakdown ofthe implant matrix and/or the rate of release of a bioactive agent in vivo from the implant matrix.
- pore-forming agents include sucrose, sodium chloride, sodium carbonate, a cellulose- based polymer, and the like.
- release rate modification agents include dimethyl citrate, triethyl citrate, ethyl heptanoate, glycerin, hexanediol, and the like.
- the composition can also include a controlled release component associated with the active agent to control its release from the composition during formation ofthe implant and/or from the formed implant.
- controlled release components include a microcapsule, microsphere, liposome, nanoparticle or other microstructure; a fiber, bead or other macrostructure; a low water-solubility salt ofthe agent; a complex or covalently-bonded conjugate ofthe agent and a carrier molecule; and the like.
- the composition can be placed in a syringe and injected into the body of an animal using a standard needle.
- the injection may be subcutaneous, intramuscular, intraperitoneal, intralesional, and the like.
- the composition can also be dispensed by brushing or squirting it onto the surface of a tissue.
- the material can also be administered as a spray from an aerosol dispensing device under pressure, from a pump dispenser, or other pressure applicator.
- the composition can be applied to an implant site such as a void, a tissue defect, surgical incision, the surface ofthe skin to cover a burn area or surface wound, and the like.
- the composition is flowable with a consistency that ranges from watery to slightly viscous to a putty or paste.
- the non-polymeric material will eventually coagulate to a microporous, solid matrix upon the dissipation ofthe organic solvent into adjacent tissue fluids.
- the non-polymeric composition can be manipulated and shaped within the defect site as it solidifies.
- the moldability ofthe composition as it hardens allows it to conform to irregularities, crevices, cracks, holes, and the like, in the implant site.
- the resulting solid matrix is biodegradable, bioabsorbable, and/or bioerodible, and will be gradually absorbed into the surrounding tissue fluids, and become disintegrated through enzymatic, chemical and/or cellular hydrolytic action.
- the present non-polymeric composition has a lower flow viscosity than polymeric compositions. Because of this property, compositions can be formulated with a high solid content and low amount of solvent to provide a fluid form that can be administered using a pressure applicator such as injection into tissue through a syringe and needle.
- the non-polymeric materials can also be used where a high rate of degradation is desired because they are single molecules and require only one hydrolysis reaction before becoming solubilized and metabolized by the body.
- the non-polymeric compositions can also be enzymatically degraded by mechanisms other than hydrolysis. As such, matrices formed from these materials are degraded from the surface resulting in a bioerodible implant.
- the invention provides a biodegradable composition composed of a biodegradable, water-coagulable, non-polymeric material and a biocompatible, non ⁇ toxic organic solvent that is miscible to dispersible in an aqueous medium.
- the organic solvent Upon implantation in the body of an animal, the organic solvent will dissipate, disperse or leach from the composition into surrounding tissue fluid, and the non-polymeric material will gradually coagulate or precipitate to form a solid, microporous matrix.
- the resulting implant has a variety of uses, as for example, as a barrier system for enhancing cell growth and tissue regeneration, delivery of a biologically-active agent such as a drug or medicament, among other applications.
- the composition and resulting solid implant are biocompatible in that neither the non-polymeric material, the solvent nor the solid matrix cause substantial tissue irritation or necrosis at the implant site.
- implant site is meant to include a site, in or on which the non-polymeric composition is applied, as for example, a soft tissue such as muscle or fat, or a hard tissue such as bone.
- implant sites include a tissue defect such as a tissue regeneration site; a void space such as a periodontal pocket, surgical incision or other formed pocket or cavity; a natural cavity such as the oral, vaginal, rectal or nasal cavities, the cul-de-sac ofthe eye, and the like; and other sites into or onto which the composition may be placed and formed into a solid implant including a skin surface defect such as a cut, scrape or burn area.
- biodegradable means that the non-polymeric material and/or matrix ofthe implant will degrade over time by the action of enzymes, by simple or enzymatically catalyzed hydrolytic action and/or by other similar mechanisms in the human body.
- bioerodible it is meant that the implant matrix will erode or degrade over time due, at least in part, to contact with substances found in the surrounding tissue fluids, cellular action, and the like.
- bioabsorbable it is meant that the non-polymeric matrix will be broken down and absorbed within the human body, for example, by a cell, a tissue, and the like.
- Non-Polymeric Material useful in the present compositions are those that are biocompatible, substantially insoluble in water and body fluids, and biodegradable and/or bioerodible within the body of an animal.
- the non-polymeric material is capable of being at least partially solubilized in a water-soluble organic solvent.
- the non-polymeric materials are also capable of coagulating or solidifying to form a solid implant matrix upon the dissipation, dispersement or leaching ofthe solvent component from the composition and contact ofthe non-polymeric material with an aqueous medium.
- the solid matrix has a firm consistency ranging from gelatinous to impressionable and moldable, to a hard, dense solid.
- Non-polymeric materials that can be used in the composition generally include any having the foregoing characteristics.
- useful non-polymeric materials include sterols such as cholesterol, stigmasterol, ⁇ -sitosterol, and estradiol; cholesteryl esters such as cholesteryl stearate; C 12 -C 2 fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, and lignoceric acid; C ] g -C 36 mono-, di- and triacylglycerides such as glyceryl monooleate, glyceryl monolinoleate, glyceryl monolaurate, glyceryl monodocosanoate, glyceryl monomyristate, glyceryl monodicenoate, glyceryl dipalmitate, glyceryl didocosanoate, glyceryl dimyristate, gly
- fatty alcohols such as cetyl alcohol, myristyl alcohol, stearyl alcohol, and cetostearyi alcohol; esters of fatty alcohols and fatty acids such as cetyl palmitate and cetearyl palmitate; anhydrides of fatty acids such as stearic anhydride; phospholipids including phosphatidylcholine (lecithin), phosphatidylserine, phosphatidylethanolamine, phosphatidylmositol, and lysoderivatives thereof; sphingosine and derivatives thereof; spingomyelins such as stearyl, palmitoyl, and tricosanyl spingomyelins; ceramides such as stearyl and palmitoyl ceramides; glycosphingolipids; lanolin and lanolin alcohols; and combinations and mixtures thereof.
- fatty alcohols such as cetyl alcohol, myristyl alcohol, stearyl alcohol, and ceto
- Preferred non-polymeric materials include cholesterol, glyceryl monostearate, glycerol tristearate, stearic acid, stearic anhydride, glyceryl monooleate, glyceryl monolinoleate, and acetylated monoglycerides.
- the non-polymeric material is combined with a compatible and suitable organic solvent to form a composition that has the desired consistency ranging from watery to viscous to a spreadable putty or paste.
- the consistency ofthe composition will vary according to factors such as the solubility ofthe non-polymeric material in the solvent, the concentration ofthe non-polymeric material in the formulation, the concentration ofthe biologically active agent in the formulation, and/or the presence of additives.
- the solubility of a non-polymeric material in a particular solvent will vary according to factors such as its crystaliinity, hydrophilicity, ionic character and lipophilicity. Accordingly, the ionic character and the concentration ofthe non- polymeric material in the solvent can be adjusted to achieve the desired solubility.
- Highly preferred non-polymeric materials are those that have low crystaliinity, nonpolar characteristics, and are more hydrophobic.
- Organic Solvents are those that are biocompatible, pharmaceutically-acceptable, and will at least partially dissolve the non-polymeric material.
- the organic solvent has a solubility in water ranging from miscible to dispersible.
- the solvent is capable of diffusing, dispersing, or leaching from the composition in situ into aqueous tissue fluid ofthe implant site such as blood serum, lymph, cerebral spinal fluid (CSF), saliva, and the like.
- the solvent has a Hildebrand (HLB) solubility ratio of from about 9-13 (cal/cm 3 )' 2 . It is preferred that the degree of polarity ofthe solvent is effective to provide at least about 5% solubility in water.
- HLB Hildebrand
- Solvents that are useful include, for example, substituted heterocyclic compounds such as N-methyl-2 -pyrrolidone (NMP) and 2-pyrrolidone (2-pyrol); esters of carbonic acid and alkyl alcohols such as propylene carbonate, ethylene carbonate and dimethyl carbonate; fatty acids such as acetic acid, lactic acid and heptanoic acid; alkyl esters of mono-, di-, and tricarboxylic acids such as 2-ethyoxyethyl acetate, ethyl acetate, methyl acetate, ethyl lactate, ethyl butyrate, diethyl malonate, diethyl glutonate, tributyl citrate, diethyl succinate, tributyrin, isopropyl myristate, dimethyl adipate, dimethyl succinate, dimethyl oxalate, dimethyl citrate, triethyl citrate, acetyl tribu
- Preferred solvents include N-methyl-2 -pyrrolidone, 2-pyrrolidone, dimethylsulfoxide, ethyl lactate, propylene carbonate, glycofurol, glycerol formal, and isopropylidene glycol.
- a mixture of solvents providing varying degrees of solubility for the non-polymeric material can be used to increase the coagulation rate ofthe non- polymeric materials that exhibit a slow coagulation or precipitation rate in an aqueous medium.
- the non-polymeric material can be combined with a mixture of a good solvent (i.e., solvent that can solubilize the non-polymeric material to a high degree) and a poorer solvent (i.e., solvent that can solubilize the non-polymeric material to a low degree) or a non-solvent (i.e., solvent in which the non-polymeric material is substantially insoluble).
- a coagulant-promoting solvent system is composed of an effective amount of a good solvent and a poorer or non-solvent such that the non-polymeric material will remain solubilized in the composition until applied to a tissue, and then coagulate or precipitate upon dissipation or diffusion of solvent from the composition into adjacent tissue fluids.
- the concentration ofthe non-polymeric material in the composition will generally accomplish rapid and effective dissipation ofthe solvent and coagulation of the non-polymer material when administered to an implant site.
- This concentration can range from about 0.01 gram ofthe non-polymer material per ml of solvent, to about 19 grams per ml of solvent, preferably from about 0.1 gram to about 6 grams per ml.
- the solvent diffuses or leaches from the composition into the aqueous medium, and the non- polymeric material coagulates to form a solid matrix.
- the non-polymeric material solidifies in situ to a solid matrix within about 1 -5 days after implantation, preferably within about 1-3 days, preferably within about 2 hours.
- the composition of non-polymeric material can be combined with a minor amount of a biodegradable, bioabsorbable thermoplastic polymer such as a polylactide, polycaprolactone, polyglycolide, or copolymer thereof, to provide a more coherent solid implant or a composition with greater viscosity so as to hold it in place while it solidifies.
- a biodegradable, bioabsorbable thermoplastic polymer such as a polylactide, polycaprolactone, polyglycolide, or copolymer thereof.
- the solid, non-polymeric matrix that is formed from the composition has a microporous structure. Pores are formed within the solid matrix ofthe implant by several means. The dissipation, dispersement or diffusion ofthe solvent out ofthe solidifying, coagulating, non-polymeric matrix into the adjacent tissue fluids may generate pores, including pore channels, in the matrix. The size ofthe pores ofthe solid implant are in the range of about 1-500 microns, and the solid matrix has a porosity in the range of about 5-95%.
- the action ofthe solvent as it moves out ofthe coagulating non- polymeric composition results in a solid matrix that is a two-layer pore structure of a highly porous inner core portion and a comparatively less porous outer microporous skin.
- the pores ofthe inner core portion are preferably substantially uniform and the skin ofthe solid implant is relatively non-porous compared to the porous nature ofthe core.
- the outer skin portion ofthe implant has pores with diameters significantly smaller in size than the pores in the inner core portion.
- the size of pores ofthe skin layer is about 0.001 microns up to about 50 microns in diameter.
- a pore-forming agent can be included in the composition to generate additional pores in the implant matrix.
- the pore-forming agent can be any organic or inorganic, pharmaceutically-acceptable substance that is substantially soluble in water or body fluid, and will dissipate from the coagulating non-polymeric material and/or the solid matrix ofthe implant into surrounding body fluid at the implant site.
- the porous matrices formed through the inclusion of a pore-forming agent have a pore structure in which the pores are substantially similar in size throughout.
- the pore-forming agent is insoluble in the organic solvent to form a uniform mixture with the non-polymeric material.
- the pore-forming agent may also be a water-immiscible substance that rapidly degrades to a water-soluble substance.
- the pore-forming agent is combined with the non-polymeric material and organic solvent in admixture before the solid matrix is formed.
- Suitable pore-forming agents that can be used in the composition include, for example, sugars such as sucrose and dextrose, salts such as sodium chloride and sodium carbonate, polymers such as hydroxylpropylcellulose, carboxymethylcellulose, polyethylene glycol and polyvinylpyrrolidone, and the like. Solid crystals that will provide a defined pore size, such as salt or sugar, are preferred.
- the solvent and/or pore-forming agent disperses, dissipates or dissolves into surrounding tissue fluids. This causes the formation of microporous channels within the coagulating matrix.
- the pore-forming agent may dissipate from the solid matrix into the surrounding tissue fluids at a rate slower than that of the solvent, or be released from the matrix over time by biodegradation or bioerosion ofthe matrix.
- the pore-forming agent dissipates from the coagulating implant matrix within a short time following implantation such that a matrix is formed with a porosity and pore structure effective to perform the particular purpose ofthe implant, as for example, a barrier system for a tissue regeneration site, a matrix for timed-release of a drug or medicament, and the like.
- Porosity ofthe solid implant matrix may be varied by the concentration of water-soluble or water-dispersible ingredients, such as the solvent and/or pore-forming agent, in the composition.
- concentration of water-soluble or water-dispersible ingredients such as the solvent and/or pore-forming agent
- a high concentration of water- soluble substances in the composition may produce a matrix having a high degree of porosity.
- concentration ofthe pore-forming agent relative to the non-polymeric material in the composition may be varied to achieve different degrees of pore- formation, or porosity, in the matrix.
- the composition will include about 0.01-1 gram of pore-forming agent per gram ofthe non-polymeric material.
- the size or diameter ofthe pores formed in the matrix ofthe solid implant can be modified according to the size and/or distribution ofthe pore-forming agent within the implant matrix.
- pore-forming agents that are relatively insoluble in the non-polymeric mixture may be selectively included in the composition according to particle size in order to generate pores having a diameter that corresponds to the size ofthe pore-forming agent.
- Pore-forming agents that are soluble in the non- polymeric mixture may be used to vary the pore size and porosity ofthe implant matrix by the pattern of distribution and/or aggregation ofthe pore-forming agent within the mixture and the coagulating and solid matrix.
- the diameter ofthe pores in the matrix are effective to deter growth of epithelial cells and enhance growth of connective tissue cells into the matrix ofthe implant. It is further preferred that the size ofthe pores and porosity ofthe matrix facilitate diffusion of nutrients and other growth-promoting substances such as growth factors, to cells which have grown into the matrix.
- the degree of porosity of the matrix provides an implant that is capable of substantially maintaining structural integrity for the desired period of time without breakage or fracturing during use.
- the diameter ofthe pores ofthe implant is about 3-500 microns, more preferably about 25-200 microns, more preferably about 75-150 microns. It is further preferred that the matrix has a porosity of about 5-95%, preferably about 25-85%, in order to provide optimum cell and tissue ingrowth into the matrix and optimum structural integrity.
- Pore diameter and distribution within the solid non-polymeric matrix may be measured, for example, according to scanning electron microscopy methods by examination of cross-sections ofthe matrix. Porosity ofthe non-polymeric matrix may be measured according to suitable methods known in the art, as for example, mercury intrusion porosimetry, specific gravity or density comparisons, calculation from scanning electronic microscopy photographs, and the like. Additionally, porosity may be calculated according to the proportion or percent of water-soluble material included in the composition. For example, a composition that contains about 30% non-polymeric material and about 70% solvent and/or other water-soluble components will generate an implant having a polymer matrix of about 70% porosity.
- the composition can provide a system for sustained, continuous delivery of drugs, medicaments and other biologically-active agents to tissues adjacent to or distant from the implant site.
- the biologically-active agent is capable of providing a local or systemic biological, physiological or therapeutic effect in the body of an animal.
- the agent may act to control infection or inflammation, enhance cell growth and tissue regeneration, control tumor growth, enhance bone growth, among other functions.
- the biologically-active agent is preferably soluble or dispersible in the non-polymeric composition to form a homogeneous mixture, and upon implantation, becomes incorporated into the implant matrix.
- the biologically-active agent is capable of being released from the matrix into the adjacent tissue fluid, and to the pertinent body tissue or organ, either adjacent to or distant from the implant site, preferably at a controlled rate.
- the release ofthe biologically-active agent from the matrix may be varied, for example, by the solubility ofthe biologically-active agent in an aqueous medium, the distribution ofthe agent within the matrix, the size, shape, porosity, and solubility and biodegradability ofthe solid matrix.
- the non-polymeric composition and solid matrix include the biologically-active agent in an amount effective to provide the desired level of biological, physiological, pharmacological and/or therapeutic effect in the animal.
- the biologically-active agent may stimulate or inhibit a biological or physiological activity within the animal.
- the lower limit ofthe amount of bioactive agent incorporated into the composition will depend on the activity of the bioactive material and the period of time desired for treatment.
- bioactive agent is gradually released from the solid matrix in vivo by diffusion, dissolution and/or biodegradation ofthe non-polymeric material.
- biologically-active agents that are useful include substances capable of preventing an infection systemically in the animal or locally at the defect site, as for example, anti-inflammatory agents such as hydrocortisone, prednisone, and the like; antibacterial agents such as penicillin, cephalosporins, bacitracin, tetracycline, doxycycline, gentamycin, quinolines, neomycin, clindamycin, kanamycin, metronidazole, and the like; antiparasitic agents such as quinacrine, chloroquine, vidarabine, and the like; antifungal agents such as nystatin, and the like; antiviral agents such as acyclovir, ribarivin, interferons, and the like; analgesic agents such as salicylic acid, acetaminophen, ibuprof
- a nerve growth promoting substance such as a ganglioside, a nerve growth factor, and the like
- a hard or soft tissue growth promoting agent such as fibronectin (FN), human growth hormone (HGH), a colony stimulating factor, bone morphogenetic protein, platelet-derived growth factor (PDGF), insulin- derived growth factor (IGF-I, IGF-II), transforming growth factor-alpha (TGF- ⁇ ), transforming growth factor- ⁇ (TGF- ⁇ ), epidermal growth factor (EGF), fibroblast growth factor (FGF), interleukin- 1 (IL-1), and the like; an osteoinductive agent or bone growth promoting substance such as bone chips, demineralized freeze-dried bone material, and the like; and antineoplastic agents such as methotrexate, 5-fluorouracil, adriamycin, vinblastine, cis
- hormones such as progesterone, testosterone, and follicle stimulating hormone (FSH) (birth control, fertility- enhancement), insulin, somatotropins, and the like; antihistamines such as diphenhydramine, chlorphencramine and the like; cardiovascular agents such as digitalis, nitroglycerine, papaverine, streptokinase and the like; anti-ulcer agents such as cimetidine hydrochloride, isopropamide iodide, and the like; bronchodilators such as metaproternal sulfate, aminophylline, and the like; vasodilators such as theophylline, niacin, minoxidil, and the like; central nervous system agents such as a tranquilizer, B- adrenergic blocking agent, dopamine, and the like; antipsychotic agents such as risperidone, olanzapine; narcotic antagonists such as naltrexone, naloxone, bupre
- the solid, non-polymeric matrix is capable of biodegradation, bioerosion and/or bioabsorption within the implant site ofthe animal.
- the implant matrix will breakdown over a period from about 2 weeks to about 12 months, preferably within about 2-12 weeks, preferably within about 14-60 days.
- the rate of breakdown ofthe implant can be controlled by varying the type, amount, and hydrophilicity ofthe non-polymeric material, by including a pore-forming agent, and/or by varying the concentrations of ingredients that comprise the non- polymeric composition.
- the amount and choice of non-polymeric material can vary the length of time the solid matrix is to be maintained within the implant site from a few days or weeks to several months.
- the implant is used to enhance cell growth and tissue regeneration, it is preferred that the solid matrix will disintegrate at a rate effective to allow displacement ofthe matrix by cell growth from the adjacent cells or tissue, preferably about 2-8 weeks.
- a wide range of release rates of the biologically-active agent from the solidified matrix from relatively fast to relatively slow, or from slow to faster, can be achieved by a number of rate release controls.
- rate release controls include adjusting the concentration ofthe non-polymeric material and bioactive agent in the composition, use of a release rate modification agent, and/or modifying the breakdown ofthe solid matrix, i.e., by varying the non-polymeric material that is used, by inclusion of a pore-forming agent, and the like.
- the rate of release ofthe bioactive agent from the solid matrix can be adjusted by varying the concentration of ingredients in the composition. For example, a composition composed of a lower concentration ofthe non-polymeric material will form a matrix from which the bioactive agent will be more readily released.
- a release rate modification agent can be included in the composition with the non-polymeric material and organic solvent to vary the rate of release of a biologically-agent from the solid matrix as desired, and provide controlled, sustained release ofthe bioactive agent.
- the release rate modification agent can be an organic substance that is water-miscible to water-dispersible, or water-insoluble.
- the release modification agent is compatible with the non-polymeric material and organic solvent of the composition, and preferably pharmaceutically-acceptable.
- the composition contains about 0.5-15%, preferably about 5-10% ofthe agent.
- the release rate modification agent can be a plasticizing compound such as epoxidized soybean oil, and other epoxidized vegetable oils.
- the release modifying agent can also be an organic solvent such as those described for solubilizing the non- polymeric material in the composition, but different from the primary organic solvent that is used.
- the non-polymeric material and bioactive agent can be solubilized in N-methyl-2 -pyrrolidone, and a minor but effective amount of another organic solvent such as dimethyl adipate can be added to the composition to modify the rate of release ofthe bioactive agent from the solidified matrix.
- Preferred organic solvent release modifying agents include propylene glycol, polyethylene glycol, ethyl heptanoate, dimethyl adipate, glyceryl triacetate, and dimethyl phthalate.
- a rate release modifying agent can be used singly or in combination.
- Suitable combinations of organic solvents as release modifying agents include, for example, glycerin/propylene glycol, sorbitol/glycerine, and the like.
- a release rate modification agent may either decrease or increase the release ofthe bioactive agent.
- a hydrophobic compound such as ethyl heptanoate can slow the release ofthe bioactive agent from the solid matrix, while a hydrophilic substance such as polyethylene glycol may increase the release ofthe bioactive agent.
- the composition can also include a structure or component for controlling release ofthe active agent from the composition as it coagulates to form the implant in situ and/or from the formed implant.
- a controlled release component can be used to facilitate the sustained release of an active agent and control the initial burst of agent from the coagulating composition, and facilitate the safe incorporation of a higher concentration of active agent into an implant. It can also improve the efficiency ofthe implant because a much greater percentage of an active agent can remain in the implant for sustained release and not be lost during the initial burst effect.
- the controlled release component can be, for example, a microstructure ranging in size from about 10 nm to about 500 microns, preferably less than about 150 microns, such as a microcapsule, microparticle such as a liposphere or microsphere, a nanoparticle, liposome, micelle, cage compound such as cyclodextrin, and the like; a macrostructure which size is larger than 500 microns, such as a fiber, film, rod, disc, cylinder, bead, and the like, including a reservoir system containing the active agent within a membrane, or a monolithic system with the active agent distributed throughout a matrix; and/or a low water-solubility salt ofthe active agent (solubility of 25 mg/l or less, 40°C, 4 hours) that includes, for example, a carboxylate anion as a counterion for the active agent, such as the ionic form of pamoic acid, tannic acid or ste
- the controlled release component can also be a molecular controlled release system such as a complex or covalently bonded conjugate ofthe agent associated with a carrier molecule to alter the water solubility and transport properties of the active agent.
- the carrier molecule can be, for example, a water-insoluble polymer such as polyglycolide, poly(DL-lactide) (PLA), polycaprolactone (PCL), and the like, and copolymers and terpolymers, and combinations and mixture thereof; a water-soluble polymer such as poly(malic acid), polyethylene glycol, poly-L-aspartic acid, poly(glutamic acid), polylysine, dextran and copolymers of N-(2-hydroxypropyl)- methacrylamide (HPMA); or a small organic molecule such as stearic acid.
- a water-insoluble polymer such as polyglycolide, poly(DL-lactide) (PLA), polycaprolactone (PCL), and the like, and copo
- a complex in which a carrier molecule is operatively associated with the active agent will break down in water but slow the release ofthe active agent from the implant.
- a complex of the active agent and carrier can optionally include a metal cation such as zinc, magnesium, calcium, and the like.
- the controlled release component can be dispersed in the composition so that it is embedded within the implant matrix upon solidification in situ.
- An implant containing a controlled release component provides at least two modes of controlled release ofthe active agent, one mode based upon the rate of release ofthe agent from the controlled release component, and another mode based upon the release ofthe agent from the implant by biodegradation, bioerosion, diffusion and/or leaching from the solid implant.
- the non-polymeric composition can be used for treating a variety of tissue defects of an animal, for example, a tissue with a void such as a periodontal pocket, a wound on the skin, a surgical incision, a bone defect, and the like.
- tissue defects of an animal
- the composition will gradually coagulate or precipitate to form a solid, microporous matrix within about 1 -5 days, preferably about 1-3 days, preferably within about 2 hours.
- the composition can be applied to a defect in bone tissue such as a fracture in an arm or leg bone, a defect in a tooth, and the like.
- bone tissue is surgically separated from the adjacent soft tissue to expose the defect, and the composition then applied to the defect, whereupon the composition hardens in situ to a solid implant.
- the solid matrix can also function as a barrier system for guided tissue regeneration by providing a surface over which cells can grow.
- the solid implant matrix provides support for new cell growth that will replace the matrix as it becomes gradually absorbed or eroded by body fluids.
- the composition can be delivered onto a tissue, for example, by injection, spraying, squirting, brushing, painting, coating, and the like. Delivery can be via a cannula, catheter, syringe with or without a needle as desired such as a 18-25 gauge needle, pressure applicator, pump, using a brush, and the like.
- the composition can be applied onto a tissue in the form of a film, for example, to provide a film dressing on the surface ofthe tissue, and/or to adhere to a tissue to another tissue or implant, among other applications.
- gingival tissue overlying the root ofthe tooth can be excised to form an envelope or pocket, and the composition delivered into the pocket and against the exposed root where it is allowed to harden to a solid matrix.
- the composition can also be delivered to a tooth defect by making an incision through the gingival tissue to expose the root, and then applying the material through the incision onto the root surface by brushing, squirting, or other means.
- an aqueous medium can be applied to the surface ofthe composition to enhance the coagulation ofthe non- polymer material.
- the coagulating composition is malleable and can be manipulated in the implant site to conform it to the contours ofthe tissue defect.
- overlying gingival tissue in a periodontal defect can be urged over the solidifying matrix, and pressure applied to the surface ofthe tissue to conform the solidifying matrix to the shape and contour ofthe root and bone.
- the solid matrix has a firm consistency that ranges from gelatinous to formable and impression-retaining to a rigid structure similar to conventional bone cement.
- a solid implant can also be formed from the non-polymeric composition outside the body ofthe animal and then inserted as a solid matrix into an implant site.
- the composition may be applied to a support surface such as glass or porcelain that has been coated with water or another aqueous medium, and additional water applied onto the surface ofthe composition.
- the solid matrix forms as the solvent dissipates into the adjacent aqueous medium.
- the implant can then be placed into the implant site ofthe animal.
- the composition can also be applied to an implantable device such as a suture, clasp, prosthesis, catheter, metal screw, bone plate, pin, a bandage such as gauze, and the like, to enhance the compatibility and or performance or function of an implantable device with a body tissue in an implant site.
- the non-polymeric system can be coated onto an implantable device, applied to a body tissue and then an implantable device implanted thereon, or the implantable device implanted and coated with the non- polymeric composition.
- the composition can be applied to the rough surface of an implantable device to enhance the compatibility ofthe device by providing a smooth surface which reduces the occurrence of abrasions from the contact of rough edges with the adjacent tissue.
- the non-polymeric system can also be used to enhance the performance or function of an implantable device.
- the composition can be applied to a gauze bandage to enhance its compatibility or adhesion with the tissue to which it is applied.
- the composition can be applied around a device such as a catheter or colostomy that is inserted through an incision into the body to secure the catheter/colostomy in place, and/or to fill the void between the device and tissue and form a tight seal to reduce bacterial infection and loss of body fluid.
- the combination ofthe non-polymeric composition and an implantable device can also be used to hold tissue in place and/or together, to adhere and/or secure the implantable device to tissue, to fill and/or seal a wound or void, among other uses.
- the non-polymeric composition and administration ofthe composition in vivo will ultimately be according to the judgment and protocol ofthe patient's attending health care professional such as a physician, or if appropriate, a dentist. Choice ofthe particular formulation of ingredients will be made by the attending health care professional.
- the solid implant can function as a structure for promotion of cell growth and tissue repair. With a bioactive agent, the implant will not only function in such capacity but will also deliver the bioactive agent to tissues and or organs ofthe animal.
- the amounts and concentrations of ingredients in the composition administered to the patient will generally be effective to accomplish the task intended. If that task is to fill a void space, a composition with an effective amount of ingredients will be administered to accomplish this task.
- a composition with an effective amount of ingredients will be administered to accomplish this task.
- the amount and release rate will follow recommendations ofthe manufacturer ofthe bioactive agent.
- the concentration of a bioactive agent in the composition will be about 0.01-400 mg per gram ofthe non-polymeric composition.
- Cholesterol was mixed with N-methyl-2 -pyrrolidone (NMP) and porcine somatotropin-A (PST-A) was added as a powder to obtain a formulation containing 30% by weight cholesterol, 60% by weight NMP, and 10% by weight PST-A.
- NMP N-methyl-2 -pyrrolidone
- PST-A porcine somatotropin-A
- the formulation was then loaded into a 1-cc polypropylene syringe and one drop of formulation was dispelled from the syringe into a tared vial containing phosphate- buffered saline solution at pH 7.4. The weight ofthe formulation added to the phosphate-buffered saline solution was recorded.
- the vial was then sealed with a Teflon®-lined screw cap and placed in a 37°C shaker bath.
- Glycerol tristearate GST was mixed with N-methyl-2-pyrrolidone (NMP), and porcine somatotropin-A (PST-A) was added to give a formulation with 30% by weight GST, 60% by weight NMP, and 10% by weight PST-A. The release of NMP, and porcine somatotropin-A (PST-A) was added to give a formulation with 30% by weight GST, 60% by weight NMP, and 10% by weight PST-A. The release of NMP, N-methyl-2-pyrrolidone (NMP), and porcine somatotropin-A (PST-A) was added to give a formulation with 30% by weight GST, 60% by weight NMP, and 10% by weight PST-A. The release of NMP, and porcine somatotropin-A (PST-A) was added to give a formulation with 30% by weight GST, 60% by weight NMP, and 10% by weight PST-A. The release of NMP, and porcine somatotropin-A (PST-
- PST-A from this formulation was determined by the same procedure described above in Example 1. Release of PST-A was sustained out to 7 days with cumulative percent releases of 45.8% after the first day, 53.6% after 2 days, 59.9% after 4 days, and 61.1% after 7 days.
- Example 3 GST was mixed with dimethyl sulfoxide (DMSO), and PST-A was added to give a formulation with 30% by weight GST, 60% by weight DMSO, and 10% by weight PST-A.
- DMSO dimethyl sulfoxide
- PST-A was added to give a formulation with 30% by weight GST, 60% by weight DMSO, and 10% by weight PST-A.
- the release of PST-A from this formulation with DMSO was substantially reduced over that obtained in Example 2 with NMP.
- the cumulative percent releases were 4.0% after the first day, 5.4% after 2 days, 8.2% after 4 days, and 8.5% after 7 days.
- Example 4 GST was mixed with DMSO, and sodium carbonate and PST-A were added as powders to give a formulation with 30% by weight GST, 50% by weight DMSO, 10% by weight sodium carbonate, and 10% by weight PST-A.
- the addition of the water-soluble pore-forming agent, sodium carbonate substantially increased the release of PST-A from the matrix compared to that without the sodium carbonate described in Example 3 above. Cumulative percent releases were 67.3% after the first day, 69.7% after 3 days, 70.3% after 5 days and 70.8% after 7 days.
- GST was mixed with triethyl citrate (TEC), and PST-A was added as a powder to give a formulation with 30% by weight GST, 60% by weight TEC, and 10% by weight PST-A.
- the release of PST-A from this formulation was intermediate between that shown with the NMP formulation in Example 2 and the DMSO formulation shown in Example 3. Cumulative percent releases were 15.4% after the first day, 15.9% after 2 days, 16.4% after 4 days, and 16.6% after 7 days.
- SAH Stearic anhydride
- Example 7 Glyceryl monolineate (GMOL) obtained from Eastman Chemical Company as Myverol 18-92 was dissolved in DMSO and doxycycline hyclate, a water- soluble antibiotic, was added as a powder to give a formulation containing 59% GMOL, 40% DMSO, and 1% doxycycline hyclate. The formulation was there loaded into a 1-cc polypropylene syringe and one drop of formulation was dispelled from the syringe into a tared vial containing phosphate-buffered saline (PBS) solution at pH 7.4. The weight ofthe formulation added to the PBS was recorded.
- PBS phosphate-buffered saline
- GMOL was dissolved in NMP and doxycycline hyclate was added to give a formulation containing 59% GMOL, 40% NMP, and 1% doxycycline hyclate.
- the release of doxycycline hyclate from this formulation was determined by the same procedure described in Example 7. This formulation containing NMP gave a faster release than the formulation in Example 7 containing DMSO, with a cumulative release of 90% after 2 hours and 100% after 5 hours.
- Example 9 GMOL was dissolved in DMSO and doxycycline hyclate was added to give a formulation containing 69% GMOL, 30% DMSO, and 1% doxycycline hyclate.
- this formulation containing a higher concentration of GMOL than in Example 7 was evaluated for release of doxycycline, it provided a more sustained release than the formulation in Example 7.
- the cumulative release of doxycycline was 65% after 2 hours and 79% after 5 hours.
- Glycerol monooleate (GMOO) obtained from Eastman Chemical Company as Myverol 18-99 was dissolved in DMSO and doxycycline hyclate was added as a powder to give a formulation containing 69% GMOO, 30% DMSO, and 1% doxycycline hyclate was added as a powder to give a formulation containing 69% GMOO, 30% DMSO, and 1% doxycycline hyclate.
- the cumulative release of doxycycline from this formulation was similar to that obtained in Example 9 with the GMOL material with 68% after 2 hours and 79% after 5 hours.
- EXAMPLE 11 GMOO was dissolved in NMP and doxycycline hydrate added to give a formulation with 69% GMOO, 30% NMP, and 1% doxycycline hyclate.
- the release of doxycycline from this formulation was comparable to that obtained in Example 10 with DMSO with cumulative releases of 70% after 2 hours and 84% after 5 hours.
- AMOG Acetylated monoglycerides obtained from Eastman Chemicals Company as Myvacet 7-07 was dissolved in NMP and doxycycline hyclate was added to give a formulation containing 69% AMOG, 30% NMP, and 1% doxycycline hyclate.
- Example 13 The same formulation of GMOL and DMSO described in Example 7 was prepared with naltrexone in place of doxycycline hyclate.
- the cumulative release of naltrexone was similar to that obtained with the more hydrophilic doxycycline hyclate in Example 7 with naltrexone cumulative releases of 77% after 2 hours and 94% after 5 hours.
- Example 8 The same formulation of GMOL with NMP described in Example 8 was prepared with naltrexone base in place of doxycycline hydrate. The cumulative release of naltrexone was 77% after 2 hours and 100% after 5 hours. This rate was lower than that obtained in Example 8 with the more hydrophilic doxycycline hyclate.
- naltrexone in place of doxycycline hyclate.
- the cumulative release of naltrexone was 59% after 2 hours and 82% after 5 hours.
- naltrexone in place of doxycycline hyclate.
- the cumulative release of naltrexone was 78% after 2 hours and 92% after 5 hours.
Abstract
Description
Claims
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DK96939495T DK0862416T3 (en) | 1995-10-27 | 1996-10-25 | Non-polymeric delayed release administration system |
AU76650/96A AU703365B2 (en) | 1995-10-27 | 1996-10-25 | Non-polymeric sustained release delivery system |
DE69623981T DE69623981T2 (en) | 1995-10-27 | 1996-10-25 | NON-POLYMERAL DELIVERED DELIVERY SYSTEMS |
AT96939495T ATE224702T1 (en) | 1995-10-27 | 1996-10-25 | NONPOLYMERIC SUSTAINED RELEASE DELIVERY SYSTEMS |
JP51679497A JP4599498B2 (en) | 1995-10-27 | 1996-10-25 | Non-polymer persistent dissociation delivery system |
CA002235919A CA2235919C (en) | 1995-10-27 | 1996-10-25 | Non-polymeric sustained release delivery system |
EP96939495A EP0862416B1 (en) | 1995-10-27 | 1996-10-25 | Non-polymeric sustained release delivery system |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/549,414 | 1995-10-27 | ||
US08/549,414 US5736152A (en) | 1995-10-27 | 1995-10-27 | Non-polymeric sustained release delivery system |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1997015285A1 true WO1997015285A1 (en) | 1997-05-01 |
Family
ID=24192944
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1996/017082 WO1997015285A1 (en) | 1995-10-27 | 1996-10-25 | Non-polymeric sustained release delivery system |
Country Status (10)
Country | Link |
---|---|
US (3) | US5736152A (en) |
EP (1) | EP0862416B1 (en) |
JP (2) | JP4599498B2 (en) |
AT (1) | ATE224702T1 (en) |
AU (1) | AU703365B2 (en) |
CA (1) | CA2235919C (en) |
DE (1) | DE69623981T2 (en) |
DK (1) | DK0862416T3 (en) |
ES (1) | ES2184895T3 (en) |
WO (1) | WO1997015285A1 (en) |
Cited By (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1997042987A1 (en) * | 1996-05-13 | 1997-11-20 | Ben-Gurion University Of The Negev | Composition and method for forming biodegradable implants in situ and uses of these implants |
WO1999013913A3 (en) * | 1997-09-15 | 1999-06-03 | Southern Biosystems Inc | High viscosity liquid controlled delivery system as a device |
EP0950403A2 (en) * | 1998-04-14 | 1999-10-20 | Atrix Laboratories, Inc. | Emulsions for in-situ delivery systems |
WO1999056725A1 (en) * | 1998-04-30 | 1999-11-11 | Ucb, S.A. | Pharmaceutical compositions capable of being gelled |
US6130200A (en) * | 1996-12-20 | 2000-10-10 | Alza Corporation | Gel composition and methods |
EP1104296A1 (en) * | 1998-07-20 | 2001-06-06 | Peptech Limited | Bioimplant formulation |
US6413536B1 (en) | 1995-06-07 | 2002-07-02 | Southern Biosystems, Inc. | High viscosity liquid controlled delivery system and medical or surgical device |
US7833543B2 (en) | 1995-06-07 | 2010-11-16 | Durect Corporation | High viscosity liquid controlled delivery system and medical or surgical device |
US8052982B2 (en) | 1998-07-20 | 2011-11-08 | Peptech Animal Health Pty Limited | Bioimplant formulation comprising lecithin and stearin |
US8846072B2 (en) | 2004-09-17 | 2014-09-30 | Durect Corporation | Controlled delivery system |
US8889174B1 (en) | 2001-06-22 | 2014-11-18 | Durect Corporation | Zero-order prolonged release coaxial implants |
US8945614B2 (en) | 2002-12-13 | 2015-02-03 | Durect Corporation | Oral drug delivery system |
US8956644B2 (en) | 2006-11-03 | 2015-02-17 | Durect Corporation | Transdermal delivery systems |
US9555113B2 (en) | 2013-03-15 | 2017-01-31 | Durect Corporation | Compositions with a rheological modifier to reduce dissolution variability |
US9592204B2 (en) | 2007-12-06 | 2017-03-14 | Durect Corporation | Oral pharmaceutical dosage forms |
US9616055B2 (en) | 2008-11-03 | 2017-04-11 | Durect Corporation | Oral pharmaceutical dosage forms |
US10471001B2 (en) | 2002-06-25 | 2019-11-12 | Durect Corporation | Short duration depot formulations |
US11083796B2 (en) | 2005-07-26 | 2021-08-10 | Durect Corporation | Peroxide removal from drug delivery vehicle |
US11400019B2 (en) | 2020-01-13 | 2022-08-02 | Durect Corporation | Sustained release drug delivery systems with reduced impurities and related methods |
Families Citing this family (552)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6207646B1 (en) * | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
US20030026782A1 (en) * | 1995-02-07 | 2003-02-06 | Arthur M. Krieg | Immunomodulatory oligonucleotides |
US5736152A (en) * | 1995-10-27 | 1998-04-07 | Atrix Laboratories, Inc. | Non-polymeric sustained release delivery system |
US6713527B2 (en) * | 1997-02-07 | 2004-03-30 | Queen's University At Kingston | Anaesthetic bone cement |
US6630168B1 (en) * | 1997-02-20 | 2003-10-07 | Biomedicines, Inc. | Gel delivery vehicles for anticellular proliferative agents |
US6406705B1 (en) * | 1997-03-10 | 2002-06-18 | University Of Iowa Research Foundation | Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant |
US6240616B1 (en) * | 1997-04-15 | 2001-06-05 | Advanced Cardiovascular Systems, Inc. | Method of manufacturing a medicated porous metal prosthesis |
US10028851B2 (en) * | 1997-04-15 | 2018-07-24 | Advanced Cardiovascular Systems, Inc. | Coatings for controlling erosion of a substrate of an implantable medical device |
US8172897B2 (en) * | 1997-04-15 | 2012-05-08 | Advanced Cardiovascular Systems, Inc. | Polymer and metal composite implantable medical devices |
US20060025328A1 (en) * | 1997-05-28 | 2006-02-02 | Burns Patrick J | Compositions suitable for controlled release of the hormone GnRH and its analogs |
US6051558A (en) * | 1997-05-28 | 2000-04-18 | Southern Biosystems, Inc. | Compositions suitable for controlled release of the hormone GnRH and its analogs |
DK0996426T3 (en) | 1997-06-05 | 2007-07-02 | Bertex Pharma Gmbh | Multiphase System |
AUPO907697A0 (en) | 1997-09-09 | 1997-10-02 | Day, Robert Edward | Chemical supplementation of bone |
US6617321B2 (en) * | 1997-09-30 | 2003-09-09 | Eli Lilly And Company | 2-methyl-thieno-benzodiazepine formulation |
US6733767B2 (en) * | 1998-03-19 | 2004-05-11 | Merck & Co., Inc. | Liquid polymeric compositions for controlled release of bioactive substances |
DE69932717T2 (en) | 1998-05-22 | 2007-08-09 | Ottawa Health Research Institute, Ottawa | METHODS AND PRODUCTS FOR INDUCING MUCOSAL IMMUNITY |
US20030022854A1 (en) | 1998-06-25 | 2003-01-30 | Dow Steven W. | Vaccines using nucleic acid-lipid complexes |
US6693086B1 (en) * | 1998-06-25 | 2004-02-17 | National Jewish Medical And Research Center | Systemic immune activation method using nucleic acid-lipid complexes |
AU6333499A (en) * | 1998-10-14 | 2000-05-01 | Cognis Deutschland Gmbh | Use of nanoscale sterols and sterol esters |
US6565874B1 (en) * | 1998-10-28 | 2003-05-20 | Atrix Laboratories | Polymeric delivery formulations of leuprolide with improved efficacy |
JP2002536966A (en) | 1998-12-30 | 2002-11-05 | ベス・イスラエル・ディーコニス・メディカル・センター・インコーポレーテッド | Characterization of the calcium channel family |
EP1154691A4 (en) * | 1999-01-05 | 2004-07-07 | Massachusetts Eye & Ear Infirm | Targeted transscleral controlled release drug delivery to the retina and choroid |
US6955661B1 (en) | 1999-01-25 | 2005-10-18 | Atrium Medical Corporation | Expandable fluoropolymer device for delivery of therapeutic agents and method of making |
US6184011B1 (en) * | 1999-03-22 | 2001-02-06 | Cbd Technologies, Ltd | Method of releasing solid matrix affinity adsorbed particulates |
EP2305324B1 (en) | 1999-03-25 | 2014-09-17 | Metabolix, Inc. | Medical devices and applications of polyhydroxyalkanoate polymers |
US6306425B1 (en) * | 1999-04-09 | 2001-10-23 | Southern Research Institute | Injectable naltrexone microsphere compositions and their use in reducing consumption of heroin and alcohol |
GB9910505D0 (en) | 1999-05-06 | 1999-07-07 | Electrosols Ltd | A method and apparatus for manufacturing consumable tablets |
US6554851B1 (en) | 1999-05-07 | 2003-04-29 | Scimed Life Systems, Inc. | Methods of sealing an injection site |
ATE479441T1 (en) | 1999-09-03 | 2010-09-15 | Brigham & Womens Hospital | METHODS AND COMPOSITIONS FOR TREATING INFLAMMATORY DISEASES USING CADHERIN-11 MODULATING AGENTS |
WO2001021163A2 (en) * | 1999-09-21 | 2001-03-29 | Emory University | Methods and compositions for treating platelet-related disorders using mpl pathway inhibitory agents |
TW524696B (en) * | 1999-11-10 | 2003-03-21 | Sumitomo Pharma | Sustained-release drug formulations |
DK1248596T3 (en) | 2000-01-11 | 2007-07-02 | Bertex Pharma Gmbh | Implants, particles |
US6575888B2 (en) * | 2000-01-25 | 2003-06-10 | Biosurface Engineering Technologies, Inc. | Bioabsorbable brachytherapy device |
NZ519992A (en) * | 2000-01-28 | 2004-04-30 | Smithkline Beecham Corp | Pharmaceutical compositions containing electrospun fiber of polymeric carrier integrated with active agent |
US7097855B1 (en) | 2000-01-31 | 2006-08-29 | Massachusetts Institute Of Technology | Transdermal thermal polymerization |
US7074803B2 (en) * | 2001-03-02 | 2006-07-11 | Durect Corporation | Opioid formulations |
US20030211974A1 (en) * | 2000-03-21 | 2003-11-13 | Brodbeck Kevin J. | Gel composition and methods |
SE516282C2 (en) * | 2000-04-04 | 2001-12-10 | Nobel Biocare Ab | Implants provided with connection and hole insertion parts and the procedure for such implants |
US7048541B2 (en) * | 2000-04-04 | 2006-05-23 | Nobel Biocare Ab | Implant having attachment and hole-insert parts, and method for producing such an implant |
AU2001253597A1 (en) * | 2000-04-12 | 2001-10-30 | Minerva Biotechnologies Corporation | Treatment of neurodegenerative disease |
EP1274459B1 (en) | 2000-04-19 | 2005-11-16 | Genentech, Inc. | Sustained release formulations comprising growth hormone |
AU7013401A (en) | 2000-06-22 | 2002-01-02 | Univ Iowa Res Found | Methods for enhancing antibody-induced cell lysis and treating cancer |
US6767899B1 (en) | 2000-08-29 | 2004-07-27 | Leiner Health Services Corp. | Composition and method for treatment of conditions having an inflammatory component |
GB0024884D0 (en) * | 2000-10-11 | 2000-11-22 | Astrazeneca Ab | Method |
JP2002128697A (en) * | 2000-10-20 | 2002-05-09 | Nonomura Tomosuke | Treating and preventing agent for oral cavity |
WO2005019269A2 (en) | 2002-11-27 | 2005-03-03 | Minerva Biotechnologies Corporation | Techniques and compositions for the diagnosis and treatment of cancer (muc1) |
ATE481640T1 (en) * | 2000-11-27 | 2010-10-15 | Minerva Biotechnologies Corp | DIAGNOSTICS, DRUG SCREENING AND TREATMENT FOR CANCER |
ES2307568T3 (en) * | 2000-12-08 | 2008-12-01 | Coley Pharmaceutical Gmbh | CPG TYPE NUCLEIC ACIDS AND SAME USE METHODS. |
US6623761B2 (en) | 2000-12-22 | 2003-09-23 | Hassan Emadeldin M. | Method of making nanoparticles of substantially water insoluble materials |
CA2439120C (en) * | 2001-02-23 | 2011-07-05 | Genentech, Inc. | Erodible polymers for injection |
EP1372604A2 (en) * | 2001-03-22 | 2004-01-02 | Battelle Memorial Institute | Manufacturing dissolvable dosage forms |
US20030050268A1 (en) * | 2001-03-29 | 2003-03-13 | Krieg Arthur M. | Immunostimulatory nucleic acid for treatment of non-allergic inflammatory diseases |
US8137699B2 (en) * | 2002-03-29 | 2012-03-20 | Trustees Of Princeton University | Process and apparatuses for preparing nanoparticle compositions with amphiphilic copolymers and their use |
WO2002083046A1 (en) | 2001-04-16 | 2002-10-24 | Pamela Howard | Wound dressing system |
WO2002089767A1 (en) | 2001-05-03 | 2002-11-14 | Massachusetts Eye And Ear Infirmary | Implantable drug delivery device and use thereof |
CA2449175A1 (en) | 2001-06-05 | 2002-12-12 | University Of Chicago | Use of methylnaltrexone to treat immune suppression |
US7455657B2 (en) * | 2001-06-19 | 2008-11-25 | Boston Scientific Scimed, Inc | Method and apparatus to modify a fluid using a selectively permeable membrane |
US7318931B2 (en) * | 2001-06-21 | 2008-01-15 | Genentech, Inc. | Sustained release formulation |
SI1446162T1 (en) * | 2001-08-17 | 2009-04-30 | Coley Pharm Gmbh | Combination motif immune stimulatory oligonucleotides with improved activity |
US6488952B1 (en) | 2001-08-28 | 2002-12-03 | John P. Kennedy | Semisolid therapeutic delivery system and combination semisolid, multiparticulate, therapeutic delivery system |
MXPA04002476A (en) | 2001-09-14 | 2004-05-31 | Anthony A Boiarski | Microfabricated nanopore device for sustained release of therapeutic agent. |
US7989018B2 (en) * | 2001-09-17 | 2011-08-02 | Advanced Cardiovascular Systems, Inc. | Fluid treatment of a polymeric coating on an implantable medical device |
US7285304B1 (en) * | 2003-06-25 | 2007-10-23 | Advanced Cardiovascular Systems, Inc. | Fluid treatment of a polymeric coating on an implantable medical device |
US6863683B2 (en) * | 2001-09-19 | 2005-03-08 | Abbott Laboratoris Vascular Entities Limited | Cold-molding process for loading a stent onto a stent delivery system |
DK1455593T3 (en) | 2001-10-06 | 2013-08-26 | Merial Ltd | PROCEDURES AND COMPOSITIONS FOR PROMOTING GROWTH AND INJURY IMMUNITY OF YOUNG ANIMALS |
WO2003034988A2 (en) * | 2001-10-19 | 2003-05-01 | Idexx Laboratories, Inc. | Injectable compositions for the controlled delivery of pharmacologically active compound |
US20030125292A1 (en) * | 2001-11-07 | 2003-07-03 | Sean Semple | Mucoscal vaccine and methods for using the same |
SE0103765D0 (en) * | 2001-11-09 | 2001-11-09 | Astrazeneca Ab | New use |
CA2467239A1 (en) | 2001-11-14 | 2003-05-22 | Alza Corporation | Catheter injectable depot compositions and uses thereof |
DE10161078A1 (en) * | 2001-12-12 | 2003-08-28 | Achim Goepferich | Matrices for the stabilization and controlled release of problem drugs |
US8685427B2 (en) * | 2002-07-31 | 2014-04-01 | Boston Scientific Scimed, Inc. | Controlled drug delivery |
US8133501B2 (en) | 2002-02-08 | 2012-03-13 | Boston Scientific Scimed, Inc. | Implantable or insertable medical devices for controlled drug delivery |
AU2003216424A1 (en) * | 2002-02-25 | 2003-10-08 | Guilford Pharmaceuticals, Inc. | Phosphorus-containing compounds with polymeric chains, and methods of making and using the same |
EP1344538A1 (en) * | 2002-03-14 | 2003-09-17 | Degradable Solutions AG | Porous biodegradable implant material and method for its fabrication |
JP2005526079A (en) * | 2002-03-15 | 2005-09-02 | サイプレス バイオサイエンス, インコーポレイテッド | NE and 5-HT reuptake inhibitors for treating visceral pain syndrome |
US7074426B2 (en) * | 2002-03-27 | 2006-07-11 | Frank Kochinke | Methods and drug delivery systems for the treatment of orofacial diseases |
US8153141B2 (en) | 2002-04-04 | 2012-04-10 | Coley Pharmaceutical Gmbh | Immunostimulatory G, U-containing oligoribonucleotides |
US20040096498A1 (en) * | 2002-04-29 | 2004-05-20 | Alvin Kershman | Oral pharmaceutical delivery system with improved sustained release |
WO2003092665A2 (en) * | 2002-05-02 | 2003-11-13 | Massachusetts Eye And Ear Infirmary | Ocular drug delivery systems and use thereof |
HUE027779T2 (en) | 2002-05-09 | 2016-11-28 | Brigham & Womens Hospital Inc | 1L1RL-1 as a cardiovascular disease marker |
US20040013649A1 (en) * | 2002-05-10 | 2004-01-22 | Inex Pharmaceuticals Corporation | Cancer vaccines and methods of using the same |
US20040009944A1 (en) * | 2002-05-10 | 2004-01-15 | Inex Pharmaceuticals Corporation | Methylated immunostimulatory oligonucleotides and methods of using the same |
US20030224023A1 (en) * | 2002-05-29 | 2003-12-04 | Unilever Home & Personal Care Usa, Division Of Conopco, Inc. | Cosmetic compositions with hydroxy amine salts of malonic acid |
IL165910A0 (en) * | 2002-07-03 | 2006-01-15 | Pericor Science Inc | Compositions of hyaluronic acid and methods of use |
US20070184089A1 (en) * | 2002-07-15 | 2007-08-09 | Alcon, Inc. | Non-Polymeric Lipophilic Pharmaceutical Implant Compositions for Intraocular Use |
DK1521573T3 (en) * | 2002-07-15 | 2008-03-25 | Alcon Inc | Non-polymeric, lipophilic, pharmaceutical implant compositions for intracellular use |
US7727549B2 (en) * | 2002-07-15 | 2010-06-01 | Alcon, Inc. | Pharmaceutical compositions for otic use |
ES2321083T3 (en) * | 2002-07-15 | 2009-06-02 | Alcon, Inc. | BIOEROSIONABLE FILM FOR THE OPHTHALMIC ADMINISTRATION OF PHARMACOS. |
IL166418A0 (en) | 2002-07-31 | 2006-01-15 | Alza Corp | Injectable depot compositions and uses thereof |
US8920826B2 (en) | 2002-07-31 | 2014-12-30 | Boston Scientific Scimed, Inc. | Medical imaging reference devices |
CA2494400A1 (en) | 2002-07-31 | 2004-02-05 | Alza Corporation | Injectable multimodal polymer depot compositions and uses thereof |
TW200410714A (en) * | 2002-08-07 | 2004-07-01 | Smithkline Beecham Corp | Electrospun amorphous pharmaceutical compositions |
US8946387B2 (en) * | 2002-08-14 | 2015-02-03 | Macrogenics, Inc. | FcγRIIB specific antibodies and methods of use thereof |
US8530627B2 (en) * | 2002-08-14 | 2013-09-10 | Macrogenics, Inc. | FcγRIIB specific antibodies and methods of use thereof |
US8044180B2 (en) * | 2002-08-14 | 2011-10-25 | Macrogenics, Inc. | FcγRIIB specific antibodies and methods of use thereof |
US8193318B2 (en) * | 2002-08-14 | 2012-06-05 | Macrogenics, Inc. | FcγRIIB specific antibodies and methods of use thereof |
WO2004016750A2 (en) * | 2002-08-14 | 2004-02-26 | Macrogenics, Inc. | FcϜRIIB-SPECIFIC ANTIBODIES AND METHODS OF USE THEREOF |
US8968730B2 (en) * | 2002-08-14 | 2015-03-03 | Macrogenics Inc. | FcγRIIB specific antibodies and methods of use thereof |
US8187593B2 (en) * | 2002-08-14 | 2012-05-29 | Macrogenics, Inc. | FcγRIIB specific antibodies and methods of use thereof |
DE10238310A1 (en) * | 2002-08-21 | 2004-03-04 | Erich Jaeger Gmbh | electrode assembly |
US20030049698A1 (en) * | 2002-10-08 | 2003-03-13 | Wang Timothy C. | Diagnosis and treatment of gastrointestinal disease |
US20060003004A1 (en) * | 2002-10-25 | 2006-01-05 | Collegium Pharmaceutical, Inc. | Pulsatile release compositions of milnacipran |
US20040121010A1 (en) * | 2002-10-25 | 2004-06-24 | Collegium Pharmaceutical, Inc. | Pulsatile release compositions of milnacipran |
MXPA05004588A (en) | 2002-10-29 | 2005-12-14 | Coley Pharmaceutical Group Ltd | Use of cpg oligonucleotides in the treatment of hepatitis c virus infection. |
US20060271168A1 (en) * | 2002-10-30 | 2006-11-30 | Klaus Kleine | Degradable medical device |
US20080305177A1 (en) * | 2002-11-14 | 2008-12-11 | Alvin Kershman | Method of administering testosterone |
WO2004043434A1 (en) * | 2002-11-14 | 2004-05-27 | Shear/Kershman Laboratories, Inc. | Oral testosterone delivery system with improved sustained release |
US7758881B2 (en) | 2004-06-30 | 2010-07-20 | Advanced Cardiovascular Systems, Inc. | Anti-proliferative and anti-inflammatory agent combination for treatment of vascular disorders with an implantable medical device |
US8435550B2 (en) | 2002-12-16 | 2013-05-07 | Abbot Cardiovascular Systems Inc. | Anti-proliferative and anti-inflammatory agent combination for treatment of vascular disorders with an implantable medical device |
US7355008B2 (en) | 2003-01-09 | 2008-04-08 | Macrogenics, Inc. | Identification and engineering of antibodies with variant Fc regions and methods of using same |
US7960512B2 (en) | 2003-01-09 | 2011-06-14 | Macrogenics, Inc. | Identification and engineering of antibodies with variant Fc regions and methods of using same |
AU2004204817C1 (en) | 2003-01-13 | 2011-01-20 | Macrogenics, Inc. | Soluble FcyR fusion proteins and methods of use thereof |
EP1592453A1 (en) * | 2003-01-28 | 2005-11-09 | Collegium Pharmaceutical, Inc. | Multiparticulate compositions of milnacipran for oral administration |
SI2325302T1 (en) | 2003-02-11 | 2016-05-31 | Shire Human Genetic Therapies, Inc. | Cells that coexpress a sulfatase and a C-formylglycine generating enzyme and methods and uses thereof |
WO2004073551A2 (en) * | 2003-02-18 | 2004-09-02 | Massachusetts Eye And Ear Infirmary | Transscleral drug delivery device and related methods |
EP1594511A2 (en) * | 2003-02-20 | 2005-11-16 | Alcon, Inc. | Formulations of glucocorticoids to treat pathologic ocular angiogenesis |
ZA200505989B (en) * | 2003-02-20 | 2006-12-27 | Alcon Inc | Use the steroids to treat ocular disorders |
WO2004078943A2 (en) * | 2003-03-04 | 2004-09-16 | California Institute Of Technology | Alternative heterocycles for dna recognition |
DE10312346A1 (en) * | 2003-03-20 | 2004-09-30 | Bayer Healthcare Ag | Controlled release system |
US20040235770A1 (en) * | 2003-04-02 | 2004-11-25 | Coley Pharmaceutical Group, Ltd. | Immunostimulatory nucleic acid oil-in-water formulations and related methods of use |
CA2534816A1 (en) | 2003-06-12 | 2004-12-23 | Evan Newell | Systems and methods for treating human inflammatory and proliferative diseases and wounds, with fatty acid metabolism inhibitors and/or glycolytic inhibitors |
KR20060019579A (en) * | 2003-06-13 | 2006-03-03 | 알콘, 인코퍼레이티드 | Formulations of non-steroidal anti-inflammatory agents to treat pathologic ocular angiogenesis |
CA2529503A1 (en) * | 2003-06-20 | 2004-12-29 | Royer Biomedical, Inc. | Drug polymer complexes |
US20050048123A1 (en) | 2003-06-26 | 2005-03-03 | Control Delivery System, Inc. | In situ gelling drug delivery system |
AR047552A1 (en) | 2003-06-26 | 2006-01-25 | Control Delivery Sys Inc | SUPPLY SYSTEMS OF BIODEGRADABLE SUSTAINED RELEASE PHARMACOS |
US20060173171A1 (en) * | 2003-08-26 | 2006-08-03 | Bamdad Cynthia C | Techniques and compositions for diagnosis and treatment of cancer (muci) |
US8021331B2 (en) * | 2003-09-15 | 2011-09-20 | Atrium Medical Corporation | Method of coating a folded medical device |
US7198675B2 (en) | 2003-09-30 | 2007-04-03 | Advanced Cardiovascular Systems | Stent mandrel fixture and method for selectively coating surfaces of a stent |
WO2005034979A2 (en) * | 2003-10-11 | 2005-04-21 | Inex Pharmaceuticals Corporation | Methods and compositions for enhancing innate immunity and antibody dependent cellular cytotoxicity |
EP1677781A4 (en) * | 2003-10-29 | 2008-11-19 | Idexx Lab Inc | Salts of pharmacologically active compounds |
EP2248895B8 (en) | 2003-12-19 | 2016-09-21 | Autotelic LLC | Combination therapy associating a TGF-beta antagonist with a chemotherapeutic agent |
US20050154343A1 (en) * | 2004-01-14 | 2005-07-14 | Mohinder Singh | Soft tip applicator for relieving mouth pain |
US7452730B2 (en) * | 2004-01-16 | 2008-11-18 | California Institute Of Technology | DNA-binding polymers |
US8048101B2 (en) | 2004-02-25 | 2011-11-01 | Femasys Inc. | Methods and devices for conduit occlusion |
US8052669B2 (en) | 2004-02-25 | 2011-11-08 | Femasys Inc. | Methods and devices for delivery of compositions to conduits |
US9238127B2 (en) | 2004-02-25 | 2016-01-19 | Femasys Inc. | Methods and devices for delivering to conduit |
US8048086B2 (en) | 2004-02-25 | 2011-11-01 | Femasys Inc. | Methods and devices for conduit occlusion |
EP1568383A3 (en) | 2004-02-27 | 2005-11-16 | Antisense Pharma GmbH | Use of an oligonucleotide or its active derivative for the preparation of a pharmaceutical composition for inhibiting the formation of metastases in cancer treatment |
US20070155685A1 (en) * | 2004-02-27 | 2007-07-05 | Karl-Hermann Schlingensiepen | Pharmaceutical composition |
SG173322A1 (en) * | 2004-04-16 | 2011-08-29 | Macrogenics Inc Dw Us | Fc gammad riib - specific antibodies and methods of use thereof |
PL1745075T3 (en) | 2004-04-21 | 2013-09-30 | Brigham & Womens Hospital Inc | Poly-n-acetyl glucosamine (pnag/dpnag)-binding peptides and methods of use thereof |
US8163030B2 (en) * | 2004-05-06 | 2012-04-24 | Degradable Solutions Ag | Biocompatible bone implant compositions and methods for repairing a bone defect |
MXPA06012601A (en) | 2004-05-10 | 2007-05-10 | Macrogenics Inc | HUMANIZED FcgammaRIIB SPECIFIC ANTIBODIES AND METHODS OF USE THEREOF. |
EP1604693A1 (en) | 2004-06-09 | 2005-12-14 | Scil Technology GmbH | In situ forming scaffold, its manufacturing and use |
US7858115B2 (en) * | 2004-06-24 | 2010-12-28 | Idexx Laboratories | Phospholipid gel compositions for drug delivery and methods of treating conditions using same |
US7618651B2 (en) * | 2004-06-24 | 2009-11-17 | Idexx Laboratories | Pharmaceutical compositions for drug delivery and methods of treating or preventing conditions using same |
US7854943B2 (en) * | 2004-06-24 | 2010-12-21 | Idexx Laboratories | Phospholipid gel compositions for drug delivery and methods of treating conditions using same |
US8568469B1 (en) | 2004-06-28 | 2013-10-29 | Advanced Cardiovascular Systems, Inc. | Stent locking element and a method of securing a stent on a delivery system |
US8241554B1 (en) | 2004-06-29 | 2012-08-14 | Advanced Cardiovascular Systems, Inc. | Method of forming a stent pattern on a tube |
US8747879B2 (en) * | 2006-04-28 | 2014-06-10 | Advanced Cardiovascular Systems, Inc. | Method of fabricating an implantable medical device to reduce chance of late inflammatory response |
US7971333B2 (en) * | 2006-05-30 | 2011-07-05 | Advanced Cardiovascular Systems, Inc. | Manufacturing process for polymetric stents |
US20060020330A1 (en) * | 2004-07-26 | 2006-01-26 | Bin Huang | Method of fabricating an implantable medical device with biaxially oriented polymers |
US8747878B2 (en) | 2006-04-28 | 2014-06-10 | Advanced Cardiovascular Systems, Inc. | Method of fabricating an implantable medical device by controlling crystalline structure |
US8778256B1 (en) | 2004-09-30 | 2014-07-15 | Advanced Cardiovascular Systems, Inc. | Deformation of a polymer tube in the fabrication of a medical article |
US7731890B2 (en) * | 2006-06-15 | 2010-06-08 | Advanced Cardiovascular Systems, Inc. | Methods of fabricating stents with enhanced fracture toughness |
US20060041102A1 (en) * | 2004-08-23 | 2006-02-23 | Advanced Cardiovascular Systems, Inc. | Implantable devices comprising biologically absorbable polymers having constant rate of degradation and methods for fabricating the same |
US9283099B2 (en) | 2004-08-25 | 2016-03-15 | Advanced Cardiovascular Systems, Inc. | Stent-catheter assembly with a releasable connection for stent retention |
US7893034B2 (en) * | 2004-09-02 | 2011-02-22 | Yale University | Regulation of oncogenes by microRNAs |
US7229471B2 (en) * | 2004-09-10 | 2007-06-12 | Advanced Cardiovascular Systems, Inc. | Compositions containing fast-leaching plasticizers for improved performance of medical devices |
WO2007053135A1 (en) * | 2004-09-14 | 2007-05-10 | Minerva Biotechnologies Corporation | Methods for diagnosis and treatment of cancer |
CA2581126A1 (en) | 2004-09-24 | 2006-04-06 | Rfe Pharma Llc | Carboxy-amido-triazoles for the localized treatment of ocular diseases |
US20160106717A1 (en) | 2004-09-24 | 2016-04-21 | Gen Pharma Holdings LLC | Cai-based systems and methods for the localized treatment of uveitis |
US20060074422A1 (en) * | 2004-09-27 | 2006-04-06 | Story Brooks J | Suture anchor and void filler combination |
US20090011116A1 (en) * | 2004-09-28 | 2009-01-08 | Atrium Medical Corporation | Reducing template with coating receptacle containing a medical device to be coated |
US9801982B2 (en) * | 2004-09-28 | 2017-10-31 | Atrium Medical Corporation | Implantable barrier device |
US8312836B2 (en) * | 2004-09-28 | 2012-11-20 | Atrium Medical Corporation | Method and apparatus for application of a fresh coating on a medical device |
US9012506B2 (en) * | 2004-09-28 | 2015-04-21 | Atrium Medical Corporation | Cross-linked fatty acid-based biomaterials |
US9000040B2 (en) | 2004-09-28 | 2015-04-07 | Atrium Medical Corporation | Cross-linked fatty acid-based biomaterials |
WO2006036967A1 (en) | 2004-09-28 | 2006-04-06 | Atrium Medical Corporation | Solubilizing a drug for use in a coating |
US8962023B2 (en) * | 2004-09-28 | 2015-02-24 | Atrium Medical Corporation | UV cured gel and method of making |
US8367099B2 (en) * | 2004-09-28 | 2013-02-05 | Atrium Medical Corporation | Perforated fatty acid films |
US8173062B1 (en) | 2004-09-30 | 2012-05-08 | Advanced Cardiovascular Systems, Inc. | Controlled deformation of a polymer tube in fabricating a medical article |
US7875233B2 (en) | 2004-09-30 | 2011-01-25 | Advanced Cardiovascular Systems, Inc. | Method of fabricating a biaxially oriented implantable medical device |
US8043553B1 (en) | 2004-09-30 | 2011-10-25 | Advanced Cardiovascular Systems, Inc. | Controlled deformation of a polymer tube with a restraining surface in fabricating a medical article |
EP3173072A1 (en) * | 2004-10-01 | 2017-05-31 | Ramscor, Inc. | Conveniently implantable sustained release drug compositions |
US8313763B2 (en) * | 2004-10-04 | 2012-11-20 | Tolmar Therapeutics, Inc. | Sustained delivery formulations of rapamycin compounds |
AU2005294382A1 (en) * | 2004-10-04 | 2006-04-20 | Qlt Usa, Inc. | Ocular delivery of polymeric delivery formulations |
WO2007024249A2 (en) | 2004-11-10 | 2007-03-01 | Macrogenics, Inc. | Engineering fc antibody regions to confer effector function |
US8535709B2 (en) * | 2004-12-13 | 2013-09-17 | Southeastern Medical Technologies, Llc | Agents for controlling biological fluids and methods of use thereof |
US20060127437A1 (en) * | 2004-12-13 | 2006-06-15 | Misty Anderson Kennedy | Semisolid system and combination semisolid, multiparticulate system for sealing tissues and/or controlling biological fluids |
US20070059350A1 (en) * | 2004-12-13 | 2007-03-15 | Kennedy John P | Agents for controlling biological fluids and methods of use thereof |
PT1838716E (en) * | 2005-01-05 | 2011-07-15 | Lilly Co Eli | Olanzapine pamoate dihydrate |
DE102005002703C5 (en) * | 2005-01-19 | 2013-07-04 | Heraeus Kulzer Gmbh | Antibiotic coating of implants and methods for antibiotic coating |
EP1848489A2 (en) * | 2005-02-16 | 2007-10-31 | Cytori Therapeutics, Inc. | Resorbable hollow devices for implantation and delivery of therapeutic agents |
US8524731B2 (en) * | 2005-03-07 | 2013-09-03 | The University Of Chicago | Use of opioid antagonists to attenuate endothelial cell proliferation and migration |
US9662325B2 (en) | 2005-03-07 | 2017-05-30 | The University Of Chicago | Use of opioid antagonists to attenuate endothelial cell proliferation and migration |
US8518962B2 (en) | 2005-03-07 | 2013-08-27 | The University Of Chicago | Use of opioid antagonists |
MX2007010833A (en) * | 2005-03-07 | 2009-02-17 | Univ Chicago | Use of opioid antagonists to attenuate endothelial cell proliferation and migration. |
EP1875244B1 (en) * | 2005-03-30 | 2019-01-23 | Minerva Biotechnologies Corporation | Proliferation of muc1 expressing cells |
DK1875244T3 (en) | 2005-03-30 | 2019-04-29 | Minerva Biotechnologies Corp | Proliferation of MUC1-Expressing Cells |
US20060224226A1 (en) * | 2005-03-31 | 2006-10-05 | Bin Huang | In-vivo radial orientation of a polymeric implantable medical device |
US8864730B2 (en) | 2005-04-12 | 2014-10-21 | Rochester Medical Corporation | Silicone rubber male external catheter with absorbent and adhesive |
US7381048B2 (en) * | 2005-04-12 | 2008-06-03 | Advanced Cardiovascular Systems, Inc. | Stents with profiles for gripping a balloon catheter and molds for fabricating stents |
EP3479844B1 (en) | 2005-04-15 | 2023-11-22 | MacroGenics, Inc. | Covalent diabodies and uses thereof |
CN101448517A (en) | 2005-04-19 | 2009-06-03 | 伊莱利利公司 | Monovalent and polyvalent synthetic polysaccharide antigens for immunological intervention in disease |
US20060241076A1 (en) * | 2005-04-26 | 2006-10-26 | Coley Pharmaceutical Gmbh | Modified oligoribonucleotide analogs with enhanced immunostimulatory activity |
WO2006119018A2 (en) * | 2005-04-29 | 2006-11-09 | Atrium Medical Corporation | Drug delivery coating for use with a medical device and methods of treating vascular injury |
DE602006004578D1 (en) | 2005-05-05 | 2009-02-12 | Antisense Pharma Gmbh | USE OF TGF-BETA2 ANTISENSE OLIGONUCLEOTIDES |
US20060257448A1 (en) * | 2005-05-10 | 2006-11-16 | The University Of Zurich | Resorbable polymer composition, implant and method of making implant |
US7291166B2 (en) * | 2005-05-18 | 2007-11-06 | Advanced Cardiovascular Systems, Inc. | Polymeric stent patterns |
US20060282028A1 (en) * | 2005-06-10 | 2006-12-14 | Howard Pamela A | Wound Management System |
KR101502920B1 (en) | 2005-06-21 | 2015-03-17 | 조마 (유에스) 엘엘씨 | IL-1β Binding antibodies and fragments thereof |
US8354384B2 (en) * | 2005-06-23 | 2013-01-15 | Yale University | Anti-aging micrornas |
US7727235B2 (en) * | 2005-06-29 | 2010-06-01 | Ethicon, Inc. | Medical fixation devices with improved torsional drive head |
US7658880B2 (en) * | 2005-07-29 | 2010-02-09 | Advanced Cardiovascular Systems, Inc. | Polymeric stent polishing method and apparatus |
US7297758B2 (en) * | 2005-08-02 | 2007-11-20 | Advanced Cardiovascular Systems, Inc. | Method for extending shelf-life of constructs of semi-crystallizable polymers |
SI1919503T1 (en) | 2005-08-10 | 2015-02-27 | Macrogenics, Inc. | Identification and engineering of antibodies with variant fc regions and methods of using same |
US20070038290A1 (en) * | 2005-08-15 | 2007-02-15 | Bin Huang | Fiber reinforced composite stents |
US7476245B2 (en) * | 2005-08-16 | 2009-01-13 | Advanced Cardiovascular Systems, Inc. | Polymeric stent patterns |
US8362086B2 (en) | 2005-08-19 | 2013-01-29 | Merial Limited | Long acting injectable formulations |
TW201402124A (en) | 2005-08-19 | 2014-01-16 | Array Biopharma Inc | 8-substituted benzoazepines as toll-like receptor modulators |
US20070045252A1 (en) * | 2005-08-23 | 2007-03-01 | Klaus Kleine | Laser induced plasma machining with a process gas |
US9248034B2 (en) * | 2005-08-23 | 2016-02-02 | Advanced Cardiovascular Systems, Inc. | Controlled disintegrating implantable medical devices |
US20070045255A1 (en) * | 2005-08-23 | 2007-03-01 | Klaus Kleine | Laser induced plasma machining with an optimized process gas |
EP1957093B1 (en) | 2005-08-29 | 2017-04-12 | SHASHOUA, Victor E. | Neuroprotective and neurorestorative methods and compositions |
JP5554496B2 (en) * | 2005-09-19 | 2014-07-23 | ニューロナセント インコーポレイテッド | Methods and compositions for stimulating neurogenesis and for inhibiting neuronal degeneration |
US9427423B2 (en) | 2009-03-10 | 2016-08-30 | Atrium Medical Corporation | Fatty-acid based particles |
US8574627B2 (en) * | 2006-11-06 | 2013-11-05 | Atrium Medical Corporation | Coated surgical mesh |
US9278161B2 (en) | 2005-09-28 | 2016-03-08 | Atrium Medical Corporation | Tissue-separating fatty acid adhesion barrier |
US8852638B2 (en) | 2005-09-30 | 2014-10-07 | Durect Corporation | Sustained release small molecule drug formulation |
US20070134244A1 (en) * | 2005-10-14 | 2007-06-14 | Alcon, Inc. | Combination treatment for pathologic ocular angiogenesis |
EP1933991A4 (en) | 2005-10-15 | 2012-05-02 | Atrium Medical Corp | Hydrophobic cross-linked gels for bioabsorbable drug carrier coatings |
AU2006312407A1 (en) * | 2005-11-09 | 2007-05-18 | Philera New Zealand Limited | Treatment of mitochondria-related diseases and improvement of age-related metabolic deficits |
US8658608B2 (en) * | 2005-11-23 | 2014-02-25 | Yale University | Modified triple-helix forming oligonucleotides for targeted mutagenesis |
DK1957647T3 (en) | 2005-11-25 | 2015-04-07 | Zoetis Belgium S A | Immunostimulatory oligoribonucleotides |
US7867547B2 (en) | 2005-12-19 | 2011-01-11 | Advanced Cardiovascular Systems, Inc. | Selectively coating luminal surfaces of stents |
JP5276448B2 (en) * | 2005-12-22 | 2013-08-28 | オークウッド ラボラトリーズ,エル.エル.シー. | Sublimable sustained release delivery system and method for producing the same |
US20070151961A1 (en) * | 2006-01-03 | 2007-07-05 | Klaus Kleine | Fabrication of an implantable medical device with a modified laser beam |
US20070156230A1 (en) * | 2006-01-04 | 2007-07-05 | Dugan Stephen R | Stents with radiopaque markers |
US7951185B1 (en) | 2006-01-06 | 2011-05-31 | Advanced Cardiovascular Systems, Inc. | Delivery of a stent at an elevated temperature |
CN101400363B (en) | 2006-01-18 | 2012-08-29 | 昌达生物科技公司 | Pharmaceutical compositions with enhanced stability |
US20070179219A1 (en) * | 2006-01-31 | 2007-08-02 | Bin Huang | Method of fabricating an implantable medical device using gel extrusion and charge induced orientation |
AU2007226752A1 (en) * | 2006-03-10 | 2007-09-20 | Macrogenics, Inc. | Identification and engineering of antibodies with variant heavy chains and methods of using same |
CN101442998B (en) * | 2006-03-16 | 2012-03-14 | 比奥纽默里克药物公司 | Anti-cancer activity augmentation compounds and formulations and methods of use thereof |
US7964210B2 (en) * | 2006-03-31 | 2011-06-21 | Abbott Cardiovascular Systems Inc. | Degradable polymeric implantable medical devices with a continuous phase and discrete phase |
WO2007120638A2 (en) * | 2006-04-12 | 2007-10-25 | President And Fellows Of Harvard College | Methods and compositions for modulating glycosylation |
US20070254012A1 (en) * | 2006-04-28 | 2007-11-01 | Ludwig Florian N | Controlled degradation and drug release in stents |
US8003156B2 (en) | 2006-05-04 | 2011-08-23 | Advanced Cardiovascular Systems, Inc. | Rotatable support elements for stents |
US7761968B2 (en) * | 2006-05-25 | 2010-07-27 | Advanced Cardiovascular Systems, Inc. | Method of crimping a polymeric stent |
US8752268B2 (en) | 2006-05-26 | 2014-06-17 | Abbott Cardiovascular Systems Inc. | Method of making stents with radiopaque markers |
US7951194B2 (en) | 2006-05-26 | 2011-05-31 | Abbott Cardiovascular Sysetms Inc. | Bioabsorbable stent with radiopaque coating |
WO2008105886A2 (en) | 2006-05-26 | 2008-09-04 | Macrogenics, Inc. | HUMANIZED FCγRIIB-SPECIFIC ANTIBODIES AND METHODS OF USE THEREOF |
US7842737B2 (en) | 2006-09-29 | 2010-11-30 | Abbott Cardiovascular Systems Inc. | Polymer blend-bioceramic composite implantable medical devices |
US20070282434A1 (en) * | 2006-05-30 | 2007-12-06 | Yunbing Wang | Copolymer-bioceramic composite implantable medical devices |
US7959940B2 (en) * | 2006-05-30 | 2011-06-14 | Advanced Cardiovascular Systems, Inc. | Polymer-bioceramic composite implantable medical devices |
US8343530B2 (en) * | 2006-05-30 | 2013-01-01 | Abbott Cardiovascular Systems Inc. | Polymer-and polymer blend-bioceramic composite implantable medical devices |
US20080058916A1 (en) * | 2006-05-31 | 2008-03-06 | Bin Huang | Method of fabricating polymeric self-expandable stent |
US8486135B2 (en) | 2006-06-01 | 2013-07-16 | Abbott Cardiovascular Systems Inc. | Implantable medical devices fabricated from branched polymers |
US20070281073A1 (en) * | 2006-06-01 | 2007-12-06 | Gale David C | Enhanced adhesion of drug delivery coatings on stents |
US20070282433A1 (en) * | 2006-06-01 | 2007-12-06 | Limon Timothy A | Stent with retention protrusions formed during crimping |
US8034287B2 (en) * | 2006-06-01 | 2011-10-11 | Abbott Cardiovascular Systems Inc. | Radiation sterilization of medical devices |
US20070286941A1 (en) * | 2006-06-13 | 2007-12-13 | Bin Huang | Surface treatment of a polymeric stent |
US8603530B2 (en) | 2006-06-14 | 2013-12-10 | Abbott Cardiovascular Systems Inc. | Nanoshell therapy |
US8048448B2 (en) | 2006-06-15 | 2011-11-01 | Abbott Cardiovascular Systems Inc. | Nanoshells for drug delivery |
US8535372B1 (en) | 2006-06-16 | 2013-09-17 | Abbott Cardiovascular Systems Inc. | Bioabsorbable stent with prohealing layer |
US8333000B2 (en) | 2006-06-19 | 2012-12-18 | Advanced Cardiovascular Systems, Inc. | Methods for improving stent retention on a balloon catheter |
US20070290412A1 (en) * | 2006-06-19 | 2007-12-20 | John Capek | Fabricating a stent with selected properties in the radial and axial directions |
CN101472610A (en) | 2006-06-20 | 2009-07-01 | 特朗斯吉有限公司 | Recombinant viral vaccine |
US8017237B2 (en) | 2006-06-23 | 2011-09-13 | Abbott Cardiovascular Systems, Inc. | Nanoshells on polymers |
US9072820B2 (en) * | 2006-06-26 | 2015-07-07 | Advanced Cardiovascular Systems, Inc. | Polymer composite stent with polymer particles |
WO2008019199A2 (en) * | 2006-06-26 | 2008-02-14 | Macrogenics, Inc. | FCγRIIB-SPECIFIC ANTIBODIES AND METHODS OF USE THEREOF |
WO2008002933A2 (en) * | 2006-06-26 | 2008-01-03 | Macrogenics, Inc. | Combination of fcgammariib antibodies and cd20-specific antibodies and methods of use thereof |
DE102006029247A1 (en) * | 2006-06-26 | 2007-12-27 | Biotronik Vi Patent Ag | Implant with a coating comprises one or more components such as cholesterol or cholesterol ester |
US8128688B2 (en) | 2006-06-27 | 2012-03-06 | Abbott Cardiovascular Systems Inc. | Carbon coating on an implantable device |
US20070299511A1 (en) * | 2006-06-27 | 2007-12-27 | Gale David C | Thin stent coating |
US7794776B1 (en) | 2006-06-29 | 2010-09-14 | Abbott Cardiovascular Systems Inc. | Modification of polymer stents with radiation |
US7740791B2 (en) * | 2006-06-30 | 2010-06-22 | Advanced Cardiovascular Systems, Inc. | Method of fabricating a stent with features by blow molding |
US20080009938A1 (en) * | 2006-07-07 | 2008-01-10 | Bin Huang | Stent with a radiopaque marker and method for making the same |
US7823263B2 (en) | 2006-07-11 | 2010-11-02 | Abbott Cardiovascular Systems Inc. | Method of removing stent islands from a stent |
KR20140109509A (en) * | 2006-07-11 | 2014-09-15 | 큐피에스 엘엘씨 | Pharmaceutical compositions for sustained release delivery of peptides |
US7757543B2 (en) | 2006-07-13 | 2010-07-20 | Advanced Cardiovascular Systems, Inc. | Radio frequency identification monitoring of stents |
US7998404B2 (en) * | 2006-07-13 | 2011-08-16 | Advanced Cardiovascular Systems, Inc. | Reduced temperature sterilization of stents |
US20080014244A1 (en) * | 2006-07-13 | 2008-01-17 | Gale David C | Implantable medical devices and coatings therefor comprising physically crosslinked block copolymers |
US7794495B2 (en) * | 2006-07-17 | 2010-09-14 | Advanced Cardiovascular Systems, Inc. | Controlled degradation of stents |
US7886419B2 (en) * | 2006-07-18 | 2011-02-15 | Advanced Cardiovascular Systems, Inc. | Stent crimping apparatus and method |
US8016879B2 (en) * | 2006-08-01 | 2011-09-13 | Abbott Cardiovascular Systems Inc. | Drug delivery after biodegradation of the stent scaffolding |
US20080091262A1 (en) * | 2006-10-17 | 2008-04-17 | Gale David C | Drug delivery after biodegradation of the stent scaffolding |
US9173733B1 (en) | 2006-08-21 | 2015-11-03 | Abbott Cardiovascular Systems Inc. | Tracheobronchial implantable medical device and methods of use |
US7923022B2 (en) * | 2006-09-13 | 2011-04-12 | Advanced Cardiovascular Systems, Inc. | Degradable polymeric implantable medical devices with continuous phase and discrete phase |
WO2008147426A2 (en) * | 2006-10-04 | 2008-12-04 | The Brigham And Women's Hospital, Inc. | Methods and compositions for immunomodulation |
US20080112961A1 (en) * | 2006-10-09 | 2008-05-15 | Macrogenics, Inc. | Identification and Engineering of Antibodies with Variant Fc Regions and Methods of Using Same |
US7645616B2 (en) * | 2006-10-20 | 2010-01-12 | The University Of Hong Kong | Use of lipocalin-2 as a diagnostic marker and therapeutic target |
US9492596B2 (en) * | 2006-11-06 | 2016-11-15 | Atrium Medical Corporation | Barrier layer with underlying medical device and one or more reinforcing support structures |
US7718649B1 (en) * | 2006-11-10 | 2010-05-18 | Pisgah Labs, Inc. | Physical states of a pharmaceutical drug substance |
EP2092941A3 (en) * | 2006-11-20 | 2009-11-18 | Lutonix, Inc. | Drug releasing coatings for medical devices |
US20080175887A1 (en) | 2006-11-20 | 2008-07-24 | Lixiao Wang | Treatment of Asthma and Chronic Obstructive Pulmonary Disease With Anti-proliferate and Anti-inflammatory Drugs |
US8425459B2 (en) | 2006-11-20 | 2013-04-23 | Lutonix, Inc. | Medical device rapid drug releasing coatings comprising a therapeutic agent and a contrast agent |
US20080276935A1 (en) | 2006-11-20 | 2008-11-13 | Lixiao Wang | Treatment of asthma and chronic obstructive pulmonary disease with anti-proliferate and anti-inflammatory drugs |
US9700704B2 (en) | 2006-11-20 | 2017-07-11 | Lutonix, Inc. | Drug releasing coatings for balloon catheters |
US9737640B2 (en) | 2006-11-20 | 2017-08-22 | Lutonix, Inc. | Drug releasing coatings for medical devices |
US8414526B2 (en) | 2006-11-20 | 2013-04-09 | Lutonix, Inc. | Medical device rapid drug releasing coatings comprising oils, fatty acids, and/or lipids |
US8414910B2 (en) | 2006-11-20 | 2013-04-09 | Lutonix, Inc. | Drug releasing coatings for medical devices |
US8652466B2 (en) * | 2006-12-08 | 2014-02-18 | Macrogenics, Inc. | Methods for the treatment of disease using immunoglobulins having Fc regions with altered affinities for FcγRactivating and FcγRinhibiting |
US8099849B2 (en) | 2006-12-13 | 2012-01-24 | Abbott Cardiovascular Systems Inc. | Optimizing fracture toughness of polymeric stent |
WO2008077145A2 (en) | 2006-12-20 | 2008-06-26 | Xoma Technology Ltd. | Treatment of il-1-beta related diseases |
US20090112197A1 (en) | 2007-10-30 | 2009-04-30 | Searete Llc | Devices configured to facilitate release of nitric oxide |
US20110190604A1 (en) * | 2006-12-22 | 2011-08-04 | Hyde Roderick A | Nitric oxide sensors and systems |
US8642093B2 (en) * | 2007-10-30 | 2014-02-04 | The Invention Science Fund I, Llc | Methods and systems for use of photolyzable nitric oxide donors |
US7862598B2 (en) * | 2007-10-30 | 2011-01-04 | The Invention Science Fund I, Llc | Devices and systems that deliver nitric oxide |
US8221690B2 (en) * | 2007-10-30 | 2012-07-17 | The Invention Science Fund I, Llc | Systems and devices that utilize photolyzable nitric oxide donors |
WO2008086529A2 (en) * | 2007-01-11 | 2008-07-17 | Yale University | Compositions and methods for targeted inactivation of hiv cell surface receptors |
DK2148691T3 (en) | 2007-02-05 | 2015-08-17 | Apellis Pharmaceuticals Inc | Compstatinanaloger for use in the treatment of inflammatory states of the respiratory system |
PT2115029E (en) | 2007-02-15 | 2015-10-26 | Tolmar Therapeutics Inc | Low burst poly-(lactide/glycolide) and methods to produce polymers |
WO2008116216A1 (en) * | 2007-03-22 | 2008-09-25 | Medical College Of Georgia Research Institute, Inc. | Compositions and methods for inhibiting cancer metastasis |
US20080243228A1 (en) * | 2007-03-28 | 2008-10-02 | Yunbing Wang | Implantable medical devices fabricated from block copolymers |
US8262723B2 (en) | 2007-04-09 | 2012-09-11 | Abbott Cardiovascular Systems Inc. | Implantable medical devices fabricated from polymer blends with star-block copolymers |
SI2644205T1 (en) | 2007-04-12 | 2018-11-30 | The Brigham And Women's Hospital, Inc. | Targeting ABCB5 for cancer therapy |
US20100179158A1 (en) * | 2007-04-20 | 2010-07-15 | Hoffman Charles S | Inhibitors of cyclic amp phosphodiesterases |
EP2152304B1 (en) | 2007-05-02 | 2018-08-22 | The Regents of the University of Michigan | Nanoemulsion therapeutic compositions and methods of using the same |
US20100285041A1 (en) * | 2007-05-17 | 2010-11-11 | Eugen Uhlmann | Class A Oligonucleotides with Immunostimulatory Potency |
MX337286B (en) | 2007-05-25 | 2016-02-22 | Indivior Uk Ltd | Sustained delivery formulations of risperidone compounds. |
US7829008B2 (en) * | 2007-05-30 | 2010-11-09 | Abbott Cardiovascular Systems Inc. | Fabricating a stent from a blow molded tube |
US7959857B2 (en) * | 2007-06-01 | 2011-06-14 | Abbott Cardiovascular Systems Inc. | Radiation sterilization of medical devices |
US20080306582A1 (en) * | 2007-06-05 | 2008-12-11 | Yunbing Wang | Implantable medical devices with elastomeric copolymer coatings |
US8202528B2 (en) * | 2007-06-05 | 2012-06-19 | Abbott Cardiovascular Systems Inc. | Implantable medical devices with elastomeric block copolymer coatings |
US8293260B2 (en) * | 2007-06-05 | 2012-10-23 | Abbott Cardiovascular Systems Inc. | Elastomeric copolymer coatings containing poly (tetramethyl carbonate) for implantable medical devices |
US8425591B1 (en) | 2007-06-11 | 2013-04-23 | Abbott Cardiovascular Systems Inc. | Methods of forming polymer-bioceramic composite medical devices with bioceramic particles |
US8524444B2 (en) * | 2007-06-15 | 2013-09-03 | President And Fellows Of Harvard College | Methods and compositions for detections and modulating O-glycosylation |
EP2158221B1 (en) | 2007-06-21 | 2018-08-29 | MacroGenics, Inc. | Covalent diabodies and uses thereof |
AU2008265600B2 (en) | 2007-06-21 | 2013-10-31 | Neuronascent, Inc. | Methods and compositions for stimulating neurogenesis and inhibiting neuronal degeneration using isothiazolopyrimidinones |
WO2009002456A2 (en) * | 2007-06-21 | 2008-12-31 | Massachusetts Institute Of Technology | Methods and compositions relating to progenitor cells |
US8048441B2 (en) | 2007-06-25 | 2011-11-01 | Abbott Cardiovascular Systems, Inc. | Nanobead releasing medical devices |
US7901452B2 (en) * | 2007-06-27 | 2011-03-08 | Abbott Cardiovascular Systems Inc. | Method to fabricate a stent having selected morphology to reduce restenosis |
US7955381B1 (en) | 2007-06-29 | 2011-06-07 | Advanced Cardiovascular Systems, Inc. | Polymer-bioceramic composite implantable medical device with different types of bioceramic particles |
WO2009022215A1 (en) | 2007-08-13 | 2009-02-19 | Pfizer Inc. | Combination motif immune stimulatory oligonucleotides with improved activity |
US7897399B2 (en) | 2007-10-30 | 2011-03-01 | The Invention Science Fund I, Llc | Nitric oxide sensors and systems |
US10080823B2 (en) | 2007-10-30 | 2018-09-25 | Gearbox Llc | Substrates for nitric oxide releasing devices |
US20090112055A1 (en) * | 2007-10-30 | 2009-04-30 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Sleeves configured to facilitate release of nitric oxide |
US7846400B2 (en) * | 2007-10-30 | 2010-12-07 | The Invention Science Fund I, Llc | Substrates for nitric oxide releasing devices |
US8980332B2 (en) | 2007-10-30 | 2015-03-17 | The Invention Science Fund I, Llc | Methods and systems for use of photolyzable nitric oxide donors |
US8877508B2 (en) * | 2007-10-30 | 2014-11-04 | The Invention Science Fund I, Llc | Devices and systems that deliver nitric oxide |
KR20100067684A (en) * | 2007-11-05 | 2010-06-21 | 보오슈 앤드 롬 인코포레이팃드 | Water-immiscible materials as vehicles for drug delivery |
PL2391650T3 (en) | 2007-12-20 | 2015-03-31 | Xoma Us Llc | Methods for the treatment of gout |
US20090181068A1 (en) * | 2008-01-14 | 2009-07-16 | Dunn Richard L | Low Viscosity Liquid Polymeric Delivery System |
WO2009111375A2 (en) * | 2008-03-01 | 2009-09-11 | Abraxis Bioscience, Llc | Treatment, diagnostic, and method for discovering antagonist using sparc specific mirnas |
WO2009113989A1 (en) | 2008-03-14 | 2009-09-17 | Bionumerik Pharmaceuticals, Inc. | Compositions and methods of use of compounds to increase cancer patient survival time |
US8685995B2 (en) * | 2008-03-21 | 2014-04-01 | The University Of Chicago | Treatment with opioid antagonists and mTOR inhibitors |
BRPI0906309A2 (en) * | 2008-04-02 | 2020-05-26 | Macrogenics, Inc | IMMUNOGLOBULIN, ANTIBODY, USE OF ANTIBODY AND PHARMACEUTICAL COMPOSITION |
ES2654937T3 (en) | 2008-04-02 | 2018-02-15 | Macrogenics, Inc. | Specific antibodies for the BCR complex and procedures for their use |
EP2385370A1 (en) | 2008-04-10 | 2011-11-09 | Massachusetts Institute of Technology (MIT) | Methods for identification and use of agents targeting cancer stem cells |
US20100227853A1 (en) * | 2008-04-18 | 2010-09-09 | Trustees Of Boston College | Inhibitors of cyclic amp phosphodiesterases |
US20110076296A1 (en) | 2008-04-25 | 2011-03-31 | Innate Pharma S.A. | TLR3 Agonist Compositions |
CN102076853A (en) * | 2008-05-07 | 2011-05-25 | 阿布拉西斯生物科学有限责任公司 | Enhancement of drug therapy by mirna |
US9486531B2 (en) * | 2008-06-03 | 2016-11-08 | Indivior Uk Limited | Dehydrated hydrogel inclusion complex of a bioactive agent with flowable drug delivery system |
CA2726763A1 (en) * | 2008-06-03 | 2009-12-10 | Tolmar Therapeutics, Inc. | Controlled release copolymer formulation with improved release kinetics |
WO2010033279A2 (en) * | 2008-06-04 | 2010-03-25 | Macrogenics, Inc. | Antibodies with altered binding to fcrn and methods of using same |
EP2303888B1 (en) | 2008-06-12 | 2015-05-06 | President and Fellows of Harvard College | Compounds for antimicrobial intervention |
EP2326304A2 (en) | 2008-07-17 | 2011-06-01 | Merial Limited | Methods for enhancing the stability of polyorthoesters and their formulations |
CA2737146A1 (en) | 2008-07-25 | 2010-01-28 | The Regents Of The University Of Colorado | Clip inhibitors and methods of modulating immune function |
US8614189B2 (en) * | 2008-09-24 | 2013-12-24 | University Of Connecticut | Carbon nanotube composite scaffolds for bone tissue engineering |
EP2349209A2 (en) * | 2008-09-26 | 2011-08-03 | Nanobio Corporation | Nanoemulsion therapeutic compositions and methods of using the same |
US9554826B2 (en) | 2008-10-03 | 2017-01-31 | Femasys, Inc. | Contrast agent injection system for sonographic imaging |
US10070888B2 (en) | 2008-10-03 | 2018-09-11 | Femasys, Inc. | Methods and devices for sonographic imaging |
KR20110069144A (en) | 2008-10-09 | 2011-06-22 | 미네르바 바이오테크놀로지 코포레이션 | Method for inducing pluripotency in cells |
EP3734281A3 (en) | 2008-11-14 | 2021-01-27 | The Brigham and Women's Hospital, Inc. | Therapeutic and diagnostic methods relating to cancer stem cells |
CA2743904A1 (en) | 2008-11-17 | 2010-05-20 | The Regents Of The University Of Michigan | Cancer vaccine compositions and methods of using the same |
KR101940059B1 (en) | 2008-12-19 | 2019-01-18 | 마크로제닉스, 인크. | Covalent diabodies and uses thereof |
US20100260677A1 (en) | 2009-03-02 | 2010-10-14 | Massachusetts Institute Of Technology | Methods and systems for treatment and/or diagnosis |
US8309356B2 (en) * | 2009-04-01 | 2012-11-13 | Yale University | Pseudocomplementary oligonucleotides for targeted gene therapy |
SI2992899T1 (en) | 2009-05-14 | 2020-10-30 | Bayer Intellectual Property Gmbh | Enhanced immune response in avian species |
JP2012528858A (en) | 2009-06-01 | 2012-11-15 | プレジデント アンド フェロウズ オブ ハーバード カレッジ | O-GlcNAc transferase inhibitor and use thereof |
US20100310623A1 (en) * | 2009-06-05 | 2010-12-09 | Laurencin Cato T | Synergetic functionalized spiral-in-tubular bone scaffolds |
US20100316673A1 (en) | 2009-06-16 | 2010-12-16 | The Regents Of The University Of Michigan | Nanoemulsion vaccines |
WO2010151682A2 (en) * | 2009-06-25 | 2010-12-29 | Rochester Medical Corporation | Silicone catheter containing chlorhexidine gluconate |
WO2011011092A1 (en) | 2009-07-22 | 2011-01-27 | University Of Massachusetts | Methods and compositions to reduce oxidative stress |
KR20120107456A (en) | 2009-07-30 | 2012-10-02 | 안티센스 파마 게엠베하 | Combination of a chemotherapeutic agent and an inhibitor of the tgf-beta system |
US20110038910A1 (en) | 2009-08-11 | 2011-02-17 | Atrium Medical Corporation | Anti-infective antimicrobial-containing biomaterials |
EP2287304A1 (en) | 2009-08-17 | 2011-02-23 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Novel treatment of patients after stent implantation or balloon dilatation and novel drug eluting stents |
CN105669553A (en) | 2009-08-18 | 2016-06-15 | 文蒂雷克斯药品公司 | Substituted benzoazepines as Toll-like receptor modulators |
EP2467380B1 (en) | 2009-08-18 | 2016-11-30 | Ventirx Pharmaceuticals, Inc. | Substituted benzoazepines as toll-like receptor modulators |
LT2486141T (en) | 2009-10-07 | 2018-05-25 | Macrogenics, Inc. | Fc region-containing polypeptides that exhibit improved effector function due to alterations of the extent of fucosylation, and methods for their use |
US8808353B2 (en) | 2010-01-30 | 2014-08-19 | Abbott Cardiovascular Systems Inc. | Crush recoverable polymer scaffolds having a low crossing profile |
US8568471B2 (en) | 2010-01-30 | 2013-10-29 | Abbott Cardiovascular Systems Inc. | Crush recoverable polymer scaffolds |
SG10201604336VA (en) | 2010-03-04 | 2016-07-28 | Macrogenics Inc | Antibodies Reactive With B7-H3, Immunologically Active Fragments Thereof And Uses Thereof |
US8802091B2 (en) | 2010-03-04 | 2014-08-12 | Macrogenics, Inc. | Antibodies reactive with B7-H3 and uses thereof |
DE102010014113A1 (en) * | 2010-04-07 | 2011-10-13 | Acino Ag | Release procedure for implants |
US20110293585A1 (en) | 2010-04-21 | 2011-12-01 | Helix Therapeutics, Inc. | Compositions and methods for treatment of lysosomal storage disorders |
WO2011133803A1 (en) | 2010-04-21 | 2011-10-27 | Helix Therapeutics, Inc. | Compositions and methods for targeted inactivation of hiv cell surface receptors |
KR20130107203A (en) | 2010-05-04 | 2013-10-01 | 더 브리검 앤드 우먼즈 하스피털, 인크. | Detection and treatment of fibrosis |
WO2011143187A2 (en) | 2010-05-10 | 2011-11-17 | University Of Connecticut | Lactoferrin -based biomaterials for tissue regeneration and drug delivery |
CA2794841C (en) | 2010-05-20 | 2021-02-23 | Ecolab Usa Inc. | Rheology modified low foaming liquid antimicrobial compositions and methods of use thereof |
US9272044B2 (en) | 2010-06-08 | 2016-03-01 | Indivior Uk Limited | Injectable flowable composition buprenorphine |
GB2513060B (en) | 2010-06-08 | 2015-01-07 | Rb Pharmaceuticals Ltd | Microparticle buprenorphine suspension |
US8658603B2 (en) | 2010-06-16 | 2014-02-25 | The Regents Of The University Of Michigan | Compositions and methods for inducing an immune response |
WO2012009707A2 (en) | 2010-07-16 | 2012-01-19 | Atrium Medical Corporation | Composition and methods for altering the rate of hydrolysis of cured oil-based materials |
SG187682A1 (en) | 2010-08-02 | 2013-03-28 | Macrogenics Inc | Covalent diabodies and uses thereof |
NZ612285A (en) | 2010-12-22 | 2015-09-25 | Bayer Ip Gmbh | Enhanced immune response in bovine species |
WO2012092539A2 (en) | 2010-12-31 | 2012-07-05 | Takeda Pharmaceutical Company Limited | Antibodies to dll4 and uses thereof |
CN106749023A (en) | 2011-01-12 | 2017-05-31 | 帆德制药股份有限公司 | As the substituted benzazepine of toll-like receptor conditioning agent |
EP3207930A1 (en) | 2011-01-12 | 2017-08-23 | VentiRx Pharmaceuticals, Inc. | Substituted benzoazepines as toll-like receptor modulators |
MY165507A (en) | 2011-02-03 | 2018-03-28 | Mirna Therapeutics Inc | Synthetic mimics of mir-34 |
EP2670849A1 (en) | 2011-02-03 | 2013-12-11 | Mirna Therapeutics, Inc. | Synthetic mimics of mir-124 |
US9707375B2 (en) | 2011-03-14 | 2017-07-18 | Rochester Medical Corporation, a subsidiary of C. R. Bard, Inc. | Catheter grip and method |
EP2699264B1 (en) | 2011-04-20 | 2018-03-14 | Medlmmune, LLC | Antibodies and other molecules that bind b7-h1 and pd-1 |
CN105148285B (en) | 2011-04-21 | 2019-02-12 | 塔夫茨大学信托人 | For the stabilized method and composition of active agent |
US9376495B2 (en) | 2011-05-21 | 2016-06-28 | Macrogenics, Inc. | Deimmunized serum-binding domains and their use in extending serum half-life |
CA2837227C (en) | 2011-06-01 | 2022-05-10 | Janus Biotherapeutics, Inc. | Novel immune system modulators |
US9353115B2 (en) | 2011-06-01 | 2016-05-31 | Janus Biotherapeutics, Inc. | Immune system modulators |
CA2842321C (en) | 2011-07-18 | 2022-05-03 | President And Fellows Of Harvard College | Engineered microbe-targeting molecules and uses thereof |
WO2013013061A1 (en) | 2011-07-19 | 2013-01-24 | University Of Vermont And State Agricultural College | Methods and compounds for treating cancer |
US8726483B2 (en) | 2011-07-29 | 2014-05-20 | Abbott Cardiovascular Systems Inc. | Methods for uniform crimping and deployment of a polymer scaffold |
WO2013020044A1 (en) | 2011-08-03 | 2013-02-07 | The Charlotte-Mecklenburg Hospital Authority D/B/A Carolinas Medical Center | Treatment of fibrosis using microrna-19b |
AU2012296613B2 (en) | 2011-08-15 | 2016-05-12 | Amplimmune, Inc. | Anti-B7-H4 antibodies and their uses |
SG10201601086WA (en) | 2011-08-18 | 2016-03-30 | Otago Innovation Ltd | Cardiovascular therapeutics |
KR101494594B1 (en) | 2011-08-30 | 2015-02-23 | 주식회사 종근당 | Sustained-release lipid pre-concentrate of pharmacologically active substance and pharmaceutical composition comprising the same |
AU2012318694B2 (en) | 2011-10-04 | 2016-12-22 | Janus Biotherapeutics, Inc. | Novel imidazole quinoline-based immune system modulators |
CA2856520C (en) | 2011-11-23 | 2021-04-06 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
US9301920B2 (en) | 2012-06-18 | 2016-04-05 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
US9173884B2 (en) | 2011-11-30 | 2015-11-03 | Trustees Of Boston College | Inhibitors of phosphodiesterase 11 (PDE11) |
EP2794657B1 (en) | 2011-12-19 | 2017-10-11 | Xoma (Us) Llc | Methods for treating acne |
US20130158132A1 (en) * | 2011-12-19 | 2013-06-20 | Aida Salatinjants | Formulation Solution Adapted To Prolong Plasma Times Of Drugs In Mammals Including Humans |
AU2013208007A1 (en) | 2012-01-09 | 2014-07-31 | The Scripps Research Institute | Humanized antibodies with ultralong CDR3 |
JP6684490B2 (en) | 2012-01-09 | 2020-04-22 | ザ・スクリップス・リサーチ・インスティテュート | Ultralong complementarity determining regions and uses thereof |
US9867880B2 (en) | 2012-06-13 | 2018-01-16 | Atrium Medical Corporation | Cured oil-hydrogel biomaterial compositions for controlled drug delivery |
US20150196640A1 (en) | 2012-06-18 | 2015-07-16 | Therapeuticsmd, Inc. | Progesterone formulations having a desirable pk profile |
US10806697B2 (en) | 2012-12-21 | 2020-10-20 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US10806740B2 (en) | 2012-06-18 | 2020-10-20 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
US20130338122A1 (en) | 2012-06-18 | 2013-12-19 | Therapeuticsmd, Inc. | Transdermal hormone replacement therapies |
CN110812470A (en) | 2012-07-11 | 2020-02-21 | 佛蒙特大学及州农业学院 | Methods and compositions for metabolic regulation |
CN104684923B (en) | 2012-07-13 | 2018-09-28 | 株式会社新日本科学 | Chiral Nuclec acid adjuvants |
EP3795694A3 (en) | 2012-10-02 | 2021-06-23 | The General Hospital Corporation d/b/a Massachusetts General Hospital | Methods relating to dna-sensing pathway related conditions |
WO2014055941A2 (en) | 2012-10-04 | 2014-04-10 | Pappalardo Juan Sabastian | Compounds and methods for targeted immune system delivery |
WO2014074805A1 (en) | 2012-11-08 | 2014-05-15 | Whitehead Institute For Biomedical Research | Selective targeting of cancer stem cells |
US9872969B2 (en) | 2012-11-20 | 2018-01-23 | Rochester Medical Corporation, a subsidiary of C.R. Bard, Inc. | Catheter in bag without additional packaging |
US10092728B2 (en) | 2012-11-20 | 2018-10-09 | Rochester Medical Corporation, a subsidiary of C.R. Bard, Inc. | Sheath for securing urinary catheter |
US9750718B2 (en) | 2012-12-12 | 2017-09-05 | The Charlotte-Mecklenburg Hospital Authority | Methods of treating hepatic fibrosis and associated diseases by regulating Rev-ERB activity |
US9872851B2 (en) | 2012-12-12 | 2018-01-23 | The Charlotte-Mecklenburg Hospital Authority | Methods of treating portal hypertension |
CA2894879A1 (en) | 2012-12-19 | 2014-06-26 | Amplimmune, Inc. | B7-h4 specific antibodies, and compositions and methods of use thereof |
US10568891B2 (en) | 2012-12-21 | 2020-02-25 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US9180091B2 (en) | 2012-12-21 | 2015-11-10 | Therapeuticsmd, Inc. | Soluble estradiol capsule for vaginal insertion |
US11246875B2 (en) | 2012-12-21 | 2022-02-15 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US11266661B2 (en) | 2012-12-21 | 2022-03-08 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US10537581B2 (en) | 2012-12-21 | 2020-01-21 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US10471072B2 (en) | 2012-12-21 | 2019-11-12 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
CA2896091C (en) | 2012-12-21 | 2018-06-19 | Amplimmune, Inc. | Anti-h7cr antibodies |
KR101586789B1 (en) | 2012-12-28 | 2016-01-19 | 주식회사 종근당 | Sustained-release lipid pre-concentrate of cationic pharmacologically active substance and pharmaceutical composition comprising the same |
KR101586791B1 (en) | 2012-12-28 | 2016-01-19 | 주식회사 종근당 | Sustained-release lipid pre-concentrate of GnRH analogues and pharmaceutical composition comprising the same |
KR101586790B1 (en) | 2012-12-28 | 2016-01-19 | 주식회사 종근당 | Sustained-release lipid pre-concentrate of anionic pharmacologically active substances and pharmaceutical composition comprising the same |
US9487587B2 (en) | 2013-03-05 | 2016-11-08 | Macrogenics, Inc. | Bispecific molecules that are immunoreactive with immune effector cells of a companion animal that express an activating receptor and cells that express B7-H3 and uses thereof |
CN105377355A (en) | 2013-03-14 | 2016-03-02 | 拇趾公司 | Method of treating infections, diseases or disorders of nail unit |
US11376329B2 (en) | 2013-03-15 | 2022-07-05 | Trustees Of Tufts College | Low molecular weight silk compositions and stabilizing silk compositions |
JP6457482B2 (en) | 2013-03-15 | 2019-01-23 | トラスティーズ オブ タフツ カレッジ | Low molecular weight silk composition and stabilization of silk composition |
CA2913312A1 (en) | 2013-05-24 | 2014-11-27 | Medimmune, Llc | Anti-b7-h5 antibodies and their uses |
WO2015010100A2 (en) | 2013-07-18 | 2015-01-22 | Fabrus, Inc. | Humanized antibodies with ultralong complementarity determining regions |
WO2015017146A2 (en) | 2013-07-18 | 2015-02-05 | Fabrus, Inc. | Antibodies with ultralong complementarity determining regions |
UA116479C2 (en) | 2013-08-09 | 2018-03-26 | Макродженікс, Інк. | Bi-specific monovalent fc diabodies that are capable of binding cd32b and cd79b and uses thereof |
EP2839842A1 (en) | 2013-08-23 | 2015-02-25 | MacroGenics, Inc. | Bi-specific monovalent diabodies that are capable of binding CD123 and CD3 and uses thereof |
EP2840091A1 (en) | 2013-08-23 | 2015-02-25 | MacroGenics, Inc. | Bi-specific diabodies that are capable of binding gpA33 and CD3 and uses thereof |
EP3043824B1 (en) | 2013-09-13 | 2022-07-06 | The Scripps Research Institute | Modified therapeutic agents and compositions thereof |
AU2014337385B2 (en) | 2013-10-15 | 2020-04-30 | The Scripps Research Institute | Chimeric antigen receptor T cell switches and uses thereof |
EP3057994B1 (en) | 2013-10-15 | 2020-09-23 | The Scripps Research Institute | Peptidic chimeric antigen receptor t cell switches and uses thereof |
EP3063171B1 (en) | 2013-11-01 | 2019-07-24 | University Of Oslo | Albumin variants and uses thereof |
US11452767B2 (en) | 2013-11-15 | 2022-09-27 | Oslo Universitetssykehus Hf | CTL peptide epitopes and antigen-specific t cells, methods for their discovery, and uses thereof |
US10801070B2 (en) | 2013-11-25 | 2020-10-13 | The Broad Institute, Inc. | Compositions and methods for diagnosing, evaluating and treating cancer |
US11725237B2 (en) | 2013-12-05 | 2023-08-15 | The Broad Institute Inc. | Polymorphic gene typing and somatic change detection using sequencing data |
US20160303242A1 (en) | 2013-12-09 | 2016-10-20 | Durect Corporation | Pharmaceutically Active Agent Complexes, Polymer Complexes, and Compositions and Methods Involving the Same |
EP3082797A4 (en) | 2013-12-18 | 2017-12-13 | The California Institute for Biomedical Research | Modified therapeutic agents, stapled peptide lipid conjugates, and compositions thereof |
EP3083658B1 (en) | 2013-12-18 | 2019-05-08 | President and Fellows of Harvard College | Crp capture/detection of gram positive bacteria |
CN106456724A (en) | 2013-12-20 | 2017-02-22 | 博德研究所 | Combination therapy with neoantigen vaccine |
JPWO2015108048A1 (en) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | Chiral nucleic acid adjuvant and antitumor agent having antitumor activity |
JPWO2015108047A1 (en) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | Chiral nucleic acid adjuvant having immunity induction activity and immunity induction activator |
EP3095460A4 (en) | 2014-01-15 | 2017-08-23 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having anti-allergic activity, and anti-allergic agent |
SG11201606714TA (en) | 2014-02-14 | 2016-09-29 | Andrew S Chi | Improved methods for the treatment of vascularizing cancers |
WO2015128461A1 (en) | 2014-02-28 | 2015-09-03 | Bayer Animal Health Gmbh | Immunostimulatory plasmids |
GB201404139D0 (en) | 2014-03-10 | 2014-04-23 | Rb Pharmaceuticals Ltd | Sustained release buprenorphine solution formulations |
WO2015168255A1 (en) | 2014-04-29 | 2015-11-05 | Whitehead Institute For Biomedical Research | Methods and compositions for targeting cancer stem cells |
PL3140269T3 (en) | 2014-05-09 | 2024-03-11 | Yale University | Hyperbranched polyglycerol-coated particles and methods of making and using thereof |
US11918695B2 (en) | 2014-05-09 | 2024-03-05 | Yale University | Topical formulation of hyperbranched polymer-coated particles |
MX2016014281A (en) | 2014-05-22 | 2017-02-22 | Therapeuticsmd Inc | Natural combination hormone replacement formulations and therapies. |
NZ726520A (en) | 2014-05-29 | 2018-12-21 | Macrogenics Inc | Tri-specific binding molecules that specifically bind to multiple cancer antigens and methods of use thereof |
TWI693232B (en) | 2014-06-26 | 2020-05-11 | 美商宏觀基因股份有限公司 | Covalently bonded diabodies having immunoreactivity with pd-1 and lag-3, and methods of use thereof |
EP3398948A3 (en) | 2014-08-22 | 2018-12-05 | Janus Biotherapeutics, Inc. | 2,4,6,7-tetrasubstituted pteridine compounds and methods of synthesis and use thereof |
WO2016033234A1 (en) | 2014-08-26 | 2016-03-03 | C.R. Bard, Inc | Urinary catheter |
US10633443B2 (en) | 2014-09-26 | 2020-04-28 | Macrogenics, Inc. | Bi-specific monovalent diabodies that are capable of binding CD19 and CD3, and uses thereof |
EP3204039B1 (en) | 2014-10-10 | 2022-06-08 | The Regents Of The University Of Michigan | Nanoemulsion compositions for preventing, suppressing or eliminating allergic and inflammatory disease |
US20160106804A1 (en) | 2014-10-15 | 2016-04-21 | Yuhua Li | Pharmaceutical composition with improved stability |
CA3002137A1 (en) | 2014-10-17 | 2016-04-21 | Salix Pharmaceuticals, Inc. | Use of methylnaltrexone to attenuate tumor progression |
EP3234193B1 (en) | 2014-12-19 | 2020-07-15 | Massachusetts Institute of Technology | Molecular biomarkers for cancer immunotherapy |
WO2016100977A1 (en) | 2014-12-19 | 2016-06-23 | The Broad Institute Inc. | Methods for profiling the t-cel- receptor repertoire |
WO2016130726A1 (en) | 2015-02-10 | 2016-08-18 | Minerva Biotechnologies Corporation | Humanized anti-muc1* antibodies |
US9999527B2 (en) | 2015-02-11 | 2018-06-19 | Abbott Cardiovascular Systems Inc. | Scaffolds having radiopaque markers |
CN107592866A (en) | 2015-02-18 | 2018-01-16 | 佛蒙特大学及州农业学院 | MCJ activators and application thereof |
CN107530416A (en) | 2015-03-05 | 2018-01-02 | 西北大学 | Virus that non-nerve infects and application thereof |
US10800828B2 (en) | 2015-03-26 | 2020-10-13 | The Scripps Research Institute | Switchable non-scFv chimeric receptors, switches, and methods of use thereof to treat cancer |
CA3019311A1 (en) | 2015-04-15 | 2016-10-20 | University Of Massachusetts | Compositions and methods for xi chromosome reactivation |
EP3283113A4 (en) | 2015-04-15 | 2018-12-05 | The California Institute for Biomedical Research | Optimized pne-based chimeric receptor t cell switches and uses thereof |
CR20230191A (en) | 2015-05-20 | 2023-07-06 | Dana Farber Cancer Inst Inc | SHARED NEOANTIGENS (Div. exp 2017-584) |
TWI773646B (en) | 2015-06-08 | 2022-08-11 | 美商宏觀基因股份有限公司 | Lag-3-binding molecules and methods of use thereof |
US9700443B2 (en) | 2015-06-12 | 2017-07-11 | Abbott Cardiovascular Systems Inc. | Methods for attaching a radiopaque marker to a scaffold |
US20190000928A1 (en) | 2015-06-17 | 2019-01-03 | The California Institute For Biomedical Research | Modified therapeutic agents and compositions thereof |
JP2018521130A (en) | 2015-07-10 | 2018-08-02 | ユニバーシティ・オブ・バーモント・アンド・ステイト・アグリカルチュラル・カレッジUniversity Of Vermont And State Agricultural College | Methods and compositions for treating drug diseases and conditions |
US10328087B2 (en) | 2015-07-23 | 2019-06-25 | Therapeuticsmd, Inc. | Formulations for solubilizing hormones |
EP3328419B1 (en) | 2015-07-30 | 2021-08-25 | MacroGenics, Inc. | Pd-1-binding molecules and methods of use thereof |
US10435457B2 (en) | 2015-08-06 | 2019-10-08 | President And Fellows Of Harvard College | Microbe-binding molecules and uses thereof |
US10457941B2 (en) | 2015-08-20 | 2019-10-29 | ASOCIACION CENTRO DE INVESTIGACION COOPERATIVA EN BIOCIENCIAS-CIC bioGUNE | Methods and compositions to treat liver diseases and conditions |
CA2998745A1 (en) | 2015-09-17 | 2017-03-23 | University Of Massachusetts | Compositions and methods for modulating fmr1 expression |
CN108925136B (en) | 2015-12-02 | 2022-02-01 | 斯特赛恩斯公司 | Antibodies specific for glycosylated BTLA (B and T lymphocyte attenuating factor) |
CN109415437B (en) | 2015-12-02 | 2022-02-01 | 斯特库伯株式会社 | Antibodies and molecules that immunospecifically bind to BTN1A1 and therapeutic uses thereof |
CR20180318A (en) | 2015-12-14 | 2018-09-19 | Macrogenics Inc | BISPECIFIC MOLECULES THAT HAVE IMMUNORREACTIVITY WITH PD-1 AND CTLA-4, AND METHODS OF USE OF THE SAME |
US20200308590A1 (en) | 2016-02-16 | 2020-10-01 | Yale University | Compositions and methods for treatment of cystic fibrosis |
US11136597B2 (en) | 2016-02-16 | 2021-10-05 | Yale University | Compositions for enhancing targeted gene editing and methods of use thereof |
WO2017173334A1 (en) | 2016-04-01 | 2017-10-05 | Checkmate Pharmaceuticals, Inc. | Fc receptor-mediated drug delivery |
WO2017173071A1 (en) | 2016-04-01 | 2017-10-05 | Therapeuticsmd, Inc. | Steroid hormone pharmaceutical composition |
WO2017173044A1 (en) | 2016-04-01 | 2017-10-05 | Therapeuticsmd Inc. | Steroid hormone compositions in medium chain oils |
CN109414489B (en) | 2016-04-08 | 2022-08-16 | 埃缇健康公司D/B/A泽尔拜尔 | Netin-1 binding antibodies and uses thereof |
CN109069633A (en) | 2016-04-15 | 2018-12-21 | 宏观基因有限公司 | Novel B7-H3- binding molecule, its antibody drug conjugate and its application method |
WO2017207623A1 (en) | 2016-05-31 | 2017-12-07 | Université de Lausanne | Mirna as biomarkers and regulators of cancer stem cells |
US20190322643A1 (en) | 2016-06-29 | 2019-10-24 | Georgia State University Research Foundation, Inc. | Histone deacetylase and histone methyltransferase inhibitors and methods of making and use of the same |
SG11201900710YA (en) | 2016-07-26 | 2019-02-27 | Bayer Animal Health Gmbh | Increased fertility in bovine species |
US10188602B2 (en) | 2016-09-29 | 2019-01-29 | Gesea Biosciences Inc. | Bioerodible implant for long-term drug delivery and associated methods of manufacture and use |
CN110022794A (en) * | 2016-10-05 | 2019-07-16 | 泰坦医药品公司 | The implantable device for drug delivery of burst release with reduction |
EP3529268A1 (en) | 2016-10-19 | 2019-08-28 | The Scripps Research Institute | Chimeric antigen receptor effector cell switches with humanized targeting moieties and/or optimized chimeric antigen receptor interacting domains and uses thereof |
EP3896451A1 (en) | 2016-11-07 | 2021-10-20 | University Of Massachusetts | Carm1 inhibitors for facioscapulohumeral muscular dystrophy |
WO2018096396A1 (en) | 2016-11-22 | 2018-05-31 | University Of Oslo | Albumin variants and uses thereof |
EP3574116A1 (en) | 2017-01-24 | 2019-12-04 | The Broad Institute, Inc. | Compositions and methods for detecting a mutant variant of a polynucleotide |
EP3576726A1 (en) | 2017-02-06 | 2019-12-11 | Massachusetts Institute Of Technology | Methods and products related to glutaminase inhibitors |
US20200113821A1 (en) | 2017-04-04 | 2020-04-16 | Yale University | Compositions and methods for in utero delivery |
US11225512B2 (en) | 2017-04-27 | 2022-01-18 | University Of New Hampshire | Compositions and methods for ceramide-elevating therapeutic strategies |
CN111051346A (en) | 2017-05-31 | 2020-04-21 | 斯特库伯株式会社 | Methods of treating cancer using antibodies and molecules that immunospecifically bind to BTN1a1 |
CA3065301A1 (en) | 2017-05-31 | 2018-12-06 | Stcube & Co., Inc. | Antibodies and molecules that immunospecifically bind to btn1a1 and the therapeutic uses thereof |
US11542331B2 (en) | 2017-06-06 | 2023-01-03 | Stcube & Co., Inc. | Methods of treating cancer using antibodies and molecules that bind to BTN1A1 or BTN1A1-ligands |
WO2019014611A2 (en) | 2017-07-14 | 2019-01-17 | University Of Massachusetts | Methods and compositions for treating inflammation |
US20220118076A1 (en) | 2017-09-07 | 2022-04-21 | University Of Oslo | Vaccine molecules |
EP3678699A1 (en) | 2017-09-07 | 2020-07-15 | University Of Oslo | Vaccine molecules |
CA3070865A1 (en) | 2017-09-19 | 2019-03-28 | C.R. Bard, Inc. | Urinary catheter bridging device, systems and methods thereof |
US11717555B2 (en) | 2017-12-18 | 2023-08-08 | Foresee Pharmaceuticals Co., Ltd. | Pharmaceutical compositions having a selected release duration |
WO2019154884A1 (en) | 2018-02-07 | 2019-08-15 | Ecole Polytechnique Federale De Lausanne (Epfl) | Method for determining cancer invasiveness and patient prognosis |
PT3773537T (en) | 2018-04-19 | 2022-04-19 | Baylor College Medicine | Stat3 inhibitors |
CN109289089B (en) * | 2018-10-15 | 2021-12-28 | 福建师范大学 | Preparation method of temperature-controlled intelligent drug release system based on titanium dioxide nanotube array |
CN109289049B (en) * | 2018-10-15 | 2021-04-02 | 福建师范大学 | Preparation method of near-infrared light-controlled intelligent drug release system based on titanium dioxide nanotube array |
EP3867365A1 (en) | 2018-10-19 | 2021-08-25 | Board of Regents, The University of Texas System | Engineered long interspersed element (line) transposons and methods of use thereof |
EP3883562A4 (en) | 2018-11-21 | 2022-08-03 | Tremeau Pharmaceuticals, Inc. | Purified forms of rofecoxib, methods of manufacture and use |
EP3677693A1 (en) | 2019-01-03 | 2020-07-08 | Ecole Polytechnique Federale De Lausanne (EPFL) EPFL-TTO | Transpochimeric gene trancripts (tcgts) as cancer biomarkers |
US20220175934A1 (en) | 2019-03-21 | 2022-06-09 | Mitotherapeutix Llc | Multivalent ligand clusters for targeted delivery of therapeutic agents |
WO2020257779A1 (en) | 2019-06-21 | 2020-12-24 | Yale University | Hydroxymethyl-modified gamma-pna compositions and methods of use thereof |
US20220243211A1 (en) | 2019-06-21 | 2022-08-04 | Yale University | Peptide nucleic acid compositions with modified hoogsteen binding segments and methods of use thereof |
WO2021022161A1 (en) | 2019-07-31 | 2021-02-04 | Yale University | Compositions and methods for treating sickle cell disease |
KR20220061977A (en) | 2019-08-12 | 2022-05-13 | 퓨리노미아 바이오테크, 아이엔씨. | Methods and compositions for promoting and enhancing T cell mediated immune response through ADCC targeting of CD39 expressing cells |
WO2021062323A1 (en) | 2019-09-26 | 2021-04-01 | Stcube & Co. | Antibodies specific to glycosylated ctla-4 and methods of use thereof |
JP2022552282A (en) | 2019-10-09 | 2022-12-15 | エスティーキューブ アンド カンパニー | Antibodies specific for glycosylated LAG3 and methods of use thereof |
CN115551594A (en) | 2019-10-24 | 2022-12-30 | 米诺陶治疗公司 | Cytokine-modified chimeric antibodies and methods of use thereof |
US10945992B1 (en) | 2019-11-13 | 2021-03-16 | Tremeau Pharmaceuticals, Inc. | Dosage forms of rofecoxib and related methods |
US11633405B2 (en) | 2020-02-07 | 2023-04-25 | Therapeuticsmd, Inc. | Steroid hormone pharmaceutical formulations |
EP4107267A1 (en) | 2020-02-21 | 2022-12-28 | Mitotherapeutix LLC | Compositions and methods for inhibiting expression of methylation-controlled j-protein (mcj) |
CA3180468A1 (en) | 2020-06-30 | 2022-01-06 | Jin Young Ko | Injectable composition comprising gnrh analogue |
US11161833B1 (en) | 2021-04-09 | 2021-11-02 | Tremeau Pharmaceuticals, Inc. | Deuterated etoricoxib, methods of manufacture, and use thereof |
WO2022232321A1 (en) | 2021-04-28 | 2022-11-03 | Minotaur Therapeutics, Inc. | Humanized chimeric bovine antibodies and methods of use |
WO2022237974A1 (en) | 2021-05-12 | 2022-11-17 | Ecole Polytechnique Federale De Lausanne (Epfl) | Krab-containing zinc finger protein and cancer |
WO2022261115A1 (en) | 2021-06-07 | 2022-12-15 | Yale University | Peptide nucleic acids for spatiotemporal control of crispr-cas binding |
WO2023056368A1 (en) | 2021-09-30 | 2023-04-06 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Cyclic peptides as non-hormonal male contraceptive agents and methods of use thereof |
WO2023148398A1 (en) | 2022-02-07 | 2023-08-10 | Var2 Pharmaceuticals Aps | Antibodies and antibody fragments and analogues specific for chondroitin sulfate |
WO2024039376A1 (en) | 2022-08-18 | 2024-02-22 | Elanco Us Inc. | Method for improving growth performance in feedlot cattle |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1988007816A1 (en) * | 1987-04-06 | 1988-10-20 | Endocon, Inc. | Flash flow fused medicinal implants |
WO1995027481A1 (en) * | 1994-04-08 | 1995-10-19 | Atrix Laboratories, Inc. | Liquid delivery compositions |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3887699A (en) * | 1969-03-24 | 1975-06-03 | Seymour Yolles | Biodegradable polymeric article for dispensing drugs |
US4093709A (en) * | 1975-01-28 | 1978-06-06 | Alza Corporation | Drug delivery devices manufactured from poly(orthoesters) and poly(orthocarbonates) |
US4148871A (en) * | 1977-10-11 | 1979-04-10 | Pitt Colin G | Sustained subdermal delivery ofdrugs using poly(ε-caprolactone) and its copolymers |
US4292965A (en) * | 1978-12-29 | 1981-10-06 | The Population Council, Inc. | Intravaginal ring |
US4341728A (en) * | 1979-12-20 | 1982-07-27 | The Population Council, Inc. | Method for making an IUD with shrinking of a medicated attachment onto a support |
US4675189A (en) * | 1980-11-18 | 1987-06-23 | Syntex (U.S.A.) Inc. | Microencapsulation of water soluble active polypeptides |
US4452775A (en) * | 1982-12-03 | 1984-06-05 | Syntex (U.S.A.) Inc. | Cholesterol matrix delivery system for sustained release of macromolecules |
US4906474A (en) * | 1983-03-22 | 1990-03-06 | Massachusetts Institute Of Technology | Bioerodible polyanhydrides for controlled drug delivery |
IL73327A (en) * | 1984-10-26 | 1988-03-31 | Tzora Furniture Ind Ltd | Infants amusement device |
US4702917A (en) * | 1985-11-18 | 1987-10-27 | Research Triangle Institute | Porous bioabsorbable polyesters |
US4938763B1 (en) * | 1988-10-03 | 1995-07-04 | Atrix Lab Inc | Biodegradable in-situ forming implants and method of producing the same |
US4906476A (en) * | 1988-12-14 | 1990-03-06 | Liposome Technology, Inc. | Novel liposome composition for sustained release of steroidal drugs in lungs |
US5324520A (en) * | 1988-12-19 | 1994-06-28 | Vipont Pharmaceutical, Inc. | Intragingival delivery systems for treatment of periodontal disease |
US5324519A (en) * | 1989-07-24 | 1994-06-28 | Atrix Laboratories, Inc. | Biodegradable polymer composition |
US5487897A (en) * | 1989-07-24 | 1996-01-30 | Atrix Laboratories, Inc. | Biodegradable implant precursor |
US5077049A (en) * | 1989-07-24 | 1991-12-31 | Vipont Pharmaceutical, Inc. | Biodegradable system for regenerating the periodontium |
EP0489743A1 (en) * | 1990-07-03 | 1992-06-17 | Vipont Pharmaceutical, Inc. | Intragingival delivery systems for treatment of periodontal disease |
SG47955A1 (en) * | 1991-06-24 | 1998-04-17 | American Cyanamid Co | Implant compositions containing a biologically active protein peptide or polypeptide |
AU2605592A (en) * | 1991-10-15 | 1993-04-22 | Atrix Laboratories, Inc. | Polymeric compositions useful as controlled release implants |
EP0560014A1 (en) * | 1992-03-12 | 1993-09-15 | Atrix Laboratories, Inc. | Biodegradable film dressing and method for its formation |
US5736152A (en) * | 1995-10-27 | 1998-04-07 | Atrix Laboratories, Inc. | Non-polymeric sustained release delivery system |
-
1995
- 1995-10-27 US US08/549,414 patent/US5736152A/en not_active Expired - Lifetime
-
1996
- 1996-10-25 JP JP51679497A patent/JP4599498B2/en not_active Expired - Fee Related
- 1996-10-25 AU AU76650/96A patent/AU703365B2/en not_active Ceased
- 1996-10-25 EP EP96939495A patent/EP0862416B1/en not_active Expired - Lifetime
- 1996-10-25 DE DE69623981T patent/DE69623981T2/en not_active Expired - Lifetime
- 1996-10-25 AT AT96939495T patent/ATE224702T1/en active
- 1996-10-25 ES ES96939495T patent/ES2184895T3/en not_active Expired - Lifetime
- 1996-10-25 WO PCT/US1996/017082 patent/WO1997015285A1/en active IP Right Grant
- 1996-10-25 DK DK96939495T patent/DK0862416T3/en active
- 1996-10-25 CA CA002235919A patent/CA2235919C/en not_active Expired - Fee Related
-
1997
- 1997-11-21 US US08/975,765 patent/US5888533A/en not_active Expired - Lifetime
-
1999
- 1999-03-30 US US09/282,036 patent/US6120789A/en not_active Expired - Lifetime
-
2008
- 2008-06-24 JP JP2008163960A patent/JP2009019038A/en active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1988007816A1 (en) * | 1987-04-06 | 1988-10-20 | Endocon, Inc. | Flash flow fused medicinal implants |
WO1995027481A1 (en) * | 1994-04-08 | 1995-10-19 | Atrix Laboratories, Inc. | Liquid delivery compositions |
Cited By (46)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6413536B1 (en) | 1995-06-07 | 2002-07-02 | Southern Biosystems, Inc. | High viscosity liquid controlled delivery system and medical or surgical device |
US5968542A (en) * | 1995-06-07 | 1999-10-19 | Southern Biosystems, Inc. | High viscosity liquid controlled delivery system as a device |
US7833543B2 (en) | 1995-06-07 | 2010-11-16 | Durect Corporation | High viscosity liquid controlled delivery system and medical or surgical device |
US7053209B1 (en) | 1995-06-07 | 2006-05-30 | Durect Corporation | High viscosity liquid controlled delivery system and medical or surgical device |
WO1997042987A1 (en) * | 1996-05-13 | 1997-11-20 | Ben-Gurion University Of The Negev | Composition and method for forming biodegradable implants in situ and uses of these implants |
US6673767B1 (en) | 1996-12-20 | 2004-01-06 | Alza Corporation | Gel composition and methods |
US6130200A (en) * | 1996-12-20 | 2000-10-10 | Alza Corporation | Gel composition and methods |
US6468961B1 (en) | 1996-12-20 | 2002-10-22 | Alza Corporation | Gel composition and methods |
US6331311B1 (en) | 1996-12-20 | 2001-12-18 | Alza Corporation | Injectable depot gel composition and method of preparing the composition |
WO1999013913A3 (en) * | 1997-09-15 | 1999-06-03 | Southern Biosystems Inc | High viscosity liquid controlled delivery system as a device |
EP0950403A3 (en) * | 1998-04-14 | 2000-04-12 | Atrix Laboratories, Inc. | Emulsions for in-situ delivery systems |
JPH11343228A (en) * | 1998-04-14 | 1999-12-14 | Atrix Lab Inc | Emulsion for in-situ delivery system |
EP0950403A2 (en) * | 1998-04-14 | 1999-10-20 | Atrix Laboratories, Inc. | Emulsions for in-situ delivery systems |
US6471970B1 (en) | 1998-04-30 | 2002-10-29 | Ucb, S.A. | Use of pharmaceutical compositions capable of being gelled in periodontology |
US6464987B1 (en) | 1998-04-30 | 2002-10-15 | Ucb, S.A. | Pharmaceutical compositions capable of being gelled |
US6818224B2 (en) | 1998-04-30 | 2004-11-16 | Ucb, S.A. | Use of gellable pharmaceutical compositions in periodontology |
WO1999056725A1 (en) * | 1998-04-30 | 1999-11-11 | Ucb, S.A. | Pharmaceutical compositions capable of being gelled |
EP1104296A1 (en) * | 1998-07-20 | 2001-06-06 | Peptech Limited | Bioimplant formulation |
US8052982B2 (en) | 1998-07-20 | 2011-11-08 | Peptech Animal Health Pty Limited | Bioimplant formulation comprising lecithin and stearin |
EP1104296B1 (en) * | 1998-07-20 | 2012-06-13 | Peptech Animal Health Pty Limited | Bioimplant formulation |
US8889174B1 (en) | 2001-06-22 | 2014-11-18 | Durect Corporation | Zero-order prolonged release coaxial implants |
US10471001B2 (en) | 2002-06-25 | 2019-11-12 | Durect Corporation | Short duration depot formulations |
US11179326B2 (en) | 2002-06-25 | 2021-11-23 | Durect Corporation | Short duration depot formulations |
US10471002B2 (en) | 2002-06-25 | 2019-11-12 | Durect Corporation | Short duration depot formulations |
US8945614B2 (en) | 2002-12-13 | 2015-02-03 | Durect Corporation | Oral drug delivery system |
US9918982B2 (en) | 2002-12-13 | 2018-03-20 | Durect Corporation | Oral drug delivery system |
US9233160B2 (en) | 2002-12-13 | 2016-01-12 | Durect Corporation | Oral drug delivery system |
US9517271B2 (en) | 2002-12-13 | 2016-12-13 | Durect Corporation | Oral drug delivery system |
US8974821B2 (en) | 2002-12-13 | 2015-03-10 | Durect Corporation | Oral drug delivery system |
US8951556B2 (en) | 2002-12-13 | 2015-02-10 | Durect Corporation | Oral drug delivery system |
US8846072B2 (en) | 2004-09-17 | 2014-09-30 | Durect Corporation | Controlled delivery system |
US11083796B2 (en) | 2005-07-26 | 2021-08-10 | Durect Corporation | Peroxide removal from drug delivery vehicle |
US8956644B2 (en) | 2006-11-03 | 2015-02-17 | Durect Corporation | Transdermal delivery systems |
US9592204B2 (en) | 2007-12-06 | 2017-03-14 | Durect Corporation | Oral pharmaceutical dosage forms |
US10206883B2 (en) | 2007-12-06 | 2019-02-19 | Durect Corporation | Oral pharamaceutical dosage forms |
US9655861B2 (en) | 2007-12-06 | 2017-05-23 | Durect Corporation | Oral pharmaceutical dosage forms |
US9884056B2 (en) | 2008-11-03 | 2018-02-06 | Durect Corporation | Oral pharmaceutical dosage forms |
US10328068B2 (en) | 2008-11-03 | 2019-06-25 | Durect Corporation | Oral pharmaceutical dosage forms |
US9616055B2 (en) | 2008-11-03 | 2017-04-11 | Durect Corporation | Oral pharmaceutical dosage forms |
US9907851B2 (en) | 2013-03-15 | 2018-03-06 | Durect Corporation | Compositions with a rheological modifier to reduce dissolution variability |
US9855333B2 (en) | 2013-03-15 | 2018-01-02 | Durect Corporation | Compositions with a rheological modifier to reduce dissolution variability |
US10300142B2 (en) | 2013-03-15 | 2019-05-28 | Durect Corporation | Compositions with a rheological modifier to reduce dissolution variability |
US9572885B2 (en) | 2013-03-15 | 2017-02-21 | Durect Corporation | Compositions with a rheological modifier to reduce dissolution variability |
US9555113B2 (en) | 2013-03-15 | 2017-01-31 | Durect Corporation | Compositions with a rheological modifier to reduce dissolution variability |
US11400019B2 (en) | 2020-01-13 | 2022-08-02 | Durect Corporation | Sustained release drug delivery systems with reduced impurities and related methods |
US11771624B2 (en) | 2020-01-13 | 2023-10-03 | Durect Corporation | Sustained release drug delivery systems with reduced impurities and related methods |
Also Published As
Publication number | Publication date |
---|---|
JP4599498B2 (en) | 2010-12-15 |
ATE224702T1 (en) | 2002-10-15 |
DE69623981T2 (en) | 2003-08-07 |
US5736152A (en) | 1998-04-07 |
AU703365B2 (en) | 1999-03-25 |
JP2001508756A (en) | 2001-07-03 |
EP0862416A1 (en) | 1998-09-09 |
US6120789A (en) | 2000-09-19 |
EP0862416B1 (en) | 2002-09-25 |
CA2235919C (en) | 2005-09-13 |
JP2009019038A (en) | 2009-01-29 |
DE69623981D1 (en) | 2002-10-31 |
US5888533A (en) | 1999-03-30 |
CA2235919A1 (en) | 1997-05-01 |
AU7665096A (en) | 1997-05-15 |
ES2184895T3 (en) | 2003-04-16 |
DK0862416T3 (en) | 2003-02-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6120789A (en) | Non-polymeric sustained release delivery system | |
ES2219079T3 (en) | CONTROLLED RELEASE COMPOSITIONS FOR THE ADMINISTRATION OF LIQUIDS WITH LOW FARMACO DISCHARGE. | |
US6071530A (en) | Method and composition for treating a bone tissue defect | |
EP1125577B1 (en) | Liquid drug delivery compositions | |
EP0537559B1 (en) | Polymeric compositions useful as controlled release implants | |
EP1100460B1 (en) | A moldable solid delivery system | |
US5702716A (en) | Polymeric compositions useful as controlled release implants | |
EP0950403B1 (en) | Emulsions for in-situ delivery systems | |
AU684931C (en) | Liquid delivery compositions | |
MXPA96004634A (en) | Compositions for controlled supply, liqui |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AL AM AT AT AU AZ BA BB BG BR BY CA CH CN CU CZ CZ DE DE DK DK EE EE ES FI FI GB GE HU IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SK TJ TM TR TT UA UG US UZ VN AM AZ BY KG KZ MD RU TJ TM |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): KE LS MW SD SZ UG AT BE CH DE DK ES FI FR GB GR IE IT LU MC |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
ENP | Entry into the national phase |
Ref document number: 2235919 Country of ref document: CA Ref country code: CA Ref document number: 2235919 Kind code of ref document: A Format of ref document f/p: F Ref country code: JP Ref document number: 1997 516794 Kind code of ref document: A Format of ref document f/p: F |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1996939495 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
WWP | Wipo information: published in national office |
Ref document number: 1996939495 Country of ref document: EP |
|
WWG | Wipo information: grant in national office |
Ref document number: 1996939495 Country of ref document: EP |