WO2008007046A1 - Polyurethane elastomers - Google Patents
Polyurethane elastomers Download PDFInfo
- Publication number
- WO2008007046A1 WO2008007046A1 PCT/GB2007/002415 GB2007002415W WO2008007046A1 WO 2008007046 A1 WO2008007046 A1 WO 2008007046A1 GB 2007002415 W GB2007002415 W GB 2007002415W WO 2008007046 A1 WO2008007046 A1 WO 2008007046A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- polymer
- peg
- ppg
- linear polymer
- polymer according
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
-
- 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
- A61K9/0031—Rectum, anus
-
- 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
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
- A61K9/0036—Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms
-
- 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
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- 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
- A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/40—High-molecular-weight compounds
- C08G18/48—Polyethers
- C08G18/4804—Two or more polyethers of different physical or chemical nature
- C08G18/4808—Mixtures of two or more polyetherdiols
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/65—Low-molecular-weight compounds having active hydrogen with high-molecular-weight compounds having active hydrogen
- C08G18/66—Compounds of groups C08G18/42, C08G18/48, or C08G18/52
- C08G18/6666—Compounds of group C08G18/48 or C08G18/52
- C08G18/667—Compounds of group C08G18/48 or C08G18/52 with compounds of group C08G18/32 or polyamines of C08G18/38
- C08G18/6674—Compounds of group C08G18/48 or C08G18/52 with compounds of group C08G18/32 or polyamines of C08G18/38 with compounds of group C08G18/3203
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/70—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the isocyanates or isothiocyanates used
- C08G18/72—Polyisocyanates or polyisothiocyanates
- C08G18/73—Polyisocyanates or polyisothiocyanates acyclic
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/70—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the isocyanates or isothiocyanates used
- C08G18/72—Polyisocyanates or polyisothiocyanates
- C08G18/74—Polyisocyanates or polyisothiocyanates cyclic
- C08G18/75—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic
- C08G18/758—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic containing two or more cycloaliphatic rings
Definitions
- the present invention relates to hydrophilic thermoplastic polyurethane elastomer polymers, suitable for the production of controlled release compositions for release of pharmaceutically active agents over a prolonged period of time.
- Their elastomeric nature provides better comfort in use, for example, in pessaries, suppositories or vaginal rings.
- cross-linked polyurethane hydrogel polymers are known from European Patent Publications EPOO 16652 and EPOO 16654. These patent specifications describe cross-linked polyurethanes formed by reacting a polyethylene oxide of equivalent weight greater than 1500 with a polyfunctional isocyanate and a trifunctional compound reactive therewith, such as an alkane triol. The resultant cross-linked polyurethane polymers are water-swellable to form a hydrogel but are water-insoluble and may be loaded with water-soluble pharmaceutically active agents.
- One particular polyurethane polymer is the reaction product of polyethylene glycol 8000, Desmodur (DMDI i.e. dicyclohexylmethane-4,4-diisocyanate) and 1,2,6-hexane triol and which has been used commercially for vaginal delivery of prostaglandins.
- polyurethane polymers possess a number of practical disadvantages. Whilst the use of a triol cross-linking agent is effective in providing polymers of relatively reproducible swelling characteristics, the percent swelling is typically 200-300% (i.e. the increase in weight of the swollen polymer divided by the weight of the dry polymer).
- Pharmaceutically active agents are loaded by contacting the polymer with an aqueous solution of pharmaceutically active agent, such that the solution becomes absorbed into the polymer, forming a hydrogel. The swollen polymer is then dried back to the chosen water content before use.
- thermoset non-thermoplastic polymer
- thermoplastic polyurethane hydrogel polymers are known from patent Publication WO2004029125.
- This patent specification describes linear thermoplastic polyurethanes formed by reacting a polyethylene glycol of molecular weight of greater than 4000 g/mol with a polyfunctional isocyanate and a bifunctional compound reactive therewith, such as an alkane diol or diamine.
- the resultant thermoplastic polyurethane polymers are water-swellable to form a hydrogel but are water-insoluble and may be loaded with water-soluble pharmaceutically active agents.
- One particular polyurethane polymer is the reaction product of polyethylene glycol 8000, Desmodur (DMDI i.e.
- dicyclohexylmethane-4,4-diisocyanate dicyclohexylmethane-4,4-diisocyanate
- 1,10-decane diol which has shown percentage-swelling from 600% up to 1700% or even above.
- This type of polymer has shown a suitability for diffusion loading and short-term delivery of relatively water-soluble drugs e.g. clindamycin phosphate, oxytocin, and misoprostol.
- relatively water-soluble drugs e.g. clindamycin phosphate, oxytocin, and misoprostol.
- a high-swelling thermoplastic polyurethane polymer possesses many practical disadvantages. Due to the high weight content and block length of PEG, the polymer is only suitable for relatively short-term release (i.e. controlled release from 10 min to only a few hours) of active agents, especially in the case of highly water-soluble drugs.
- the low hydrophobic content i.e. low amount of hydrophobic compound e.g. decanediol (DD) or dodecanediol (DDD) makes the polymer inappropriate for hydrophobic drugs and thus restricts its use.
- Hydrophilic and hydrophobic drugs need to have interactions with both of the phases in order for their release to be controlled by the polymer structure. Further, the imbalance between hydrophobic and hydrophilic compounds hampers microphase separation, which reduces the mechanical strength of the polymer in both the dry and wet state.
- the final polymer is rigid and the processing temperature relatively high.
- the swelling percentage of high-swelling thermoplastic polyurethanes is typically 200-1700% and is dependent on the PEG content and/or the length of PEG block.
- Pharmaceutically active agents can be loaded by using the same method as described above for the conventional cross-linked polyurethane, as well as melt mixing drug and polymer. The release time and profiles obtained for the high swelling and crosslinked polyurethane polymers are, however, very similar.
- Patent specification WO 94/22934 discloses the production of a linear random block copolymer from polyethylene oxide (number average molecular weight 1000 to 12,000), a diamine and a diisocyanate. Yu et al. Biomaterials 12 (1991) March, No.2, page 119-120 discloses the use of polyurethane hydrogels formed of polyethylene glycol (number average molecular weight of 5830) and a low molecular weight polypropylene glycol (molecular weight 425) and a diisocyanate.
- Patent specification US 4,202,880 discloses the production of polyurethanes from polyethylene glycol (molecular weight 400-20,000), an alkaline glycol containing from 2-6 carbon atoms and a diisocyanate.
- Patent specification US 4,235,988 is a similar disclosure, although the preferred PEG range is 600-6,000.
- the object of the present invention is to provide a hydrophilic thermoplastic polyurethane elastomer, which can be processed and mixed with an active agent at the temperature below the degradation temperature of the active agent by using conventional polymer processing systems, e.g. melt mixer, extruder and injection moulding machine.
- An additional objective of the present invention is to enhance the melt viscosity, to increase elasticity and to lower the crystallinity of the polymer in order to apply conventional melt processing techniques e.g. extrusion and injection moulding, as well as different types of solvents to the formation of drug loaded resilient controlled release devices of any chosen shape.
- thermoplastic polyurethane elastomers having suitable melt processing properties for drug loading and elasticity at body temperature, as well as suitable drug release characteristics, may be obtained by reacting a polyethylene glycol or polypropylene glycol with a diol or other difunctional compound, and a PPG-PEG-PPG or PEG-PPG-PEG block copolymer and a difunctional isocyanate.
- PEG stands for polyethylene glycol
- PPG stands for polypropylene glycol
- the present invention provides a hydrophilic thermoplastic polyurethane elastomer polymer obtainable by reacting together:
- thermoplastic polyurethane elastomer produced is swellable in water to a specific degree, depending upon the ratio of the four components (a), (b), (c) and (d), for example from 1% up to 200% (e.g. 20 to 100%) thus better controlling the release of pharmaceutically active agents from the high-swelling, PEG-based linear polyurethane.
- the polymer of the invention is also soluble in certain organic solvents, such as dichloromethane, l-methyl-2-pyrrolidone (NMP) and tetrahydrofuran, which allows the polymer to be dissolved and cast into films or coatings. It also allows thermally unstable active agents of poor water solubility but which are soluble in organic solvents, to be loaded into the polymer.
- these polyurethane elastomers Due to the unique combination of starting components, these polyurethane elastomers have a composition that can control the release of active compounds from a few days up to a few months.
- Polyether polyols contain the repeating ether linkage -R-O-R- and have two or more hydroxyl groups as terminal functional groups. They are manufactured by the catalysed addition of epoxides to an initiator (anionic ring-opening polymerisation). The most important of the cyclic ethers by far are ethylene oxide and propylene oxide. These oxides react with active hydrogen-containing compounds (initiators), such as water, glycols, polyols and amines. A catalyst may or may not be used. Potassium hydroxide or sodium hydroxide is the basic catalyst most often employed. After the desired degree of polymerisation has been achieved, the catalyst is neutralized, removed by filtration and additives such as antioxidants are added.
- compositions of varying structures, chain lengths and molecular weights is possible.
- oxide or oxides By selecting the oxide or oxides, initiator, and reaction conditions and catalysts, it is possible to polymerise a series of polyether polyols that range from low-molecular-weight polyglycols to high-molecular-weight polymers. Since these polymers contain repeating alkylene oxide units, they are often referred to as polyalkylene glycols or polyglycols. Most polyether polyols are produced for polyurethane applications.
- Polyethylene glycols contain the repeat unit (-CH 2 CH 2 O-) and are conveniently prepared by the addition of ethylene oxide to ethylene glycol to produce a difunctional polyethylene glycol structure HO(CH 2 CH 2 O) n H wherein n is an integer of varying size depending on the molecular weight of the polyethylene glycol.
- Polyethylene glycols used in the present invention are generally linear polyethylene glycols i.e. diols having molecular weights of 200 to 35,000 g/mol. (generally 400 to 2000).
- Polypropylene glycols are polymers of propylene oxide and thus contain the repeat unit (-CH 2 (CH 3 )CH 2 O-).
- Polypropylene glycol has unique physical and chemical properties due to the co-occurance of both primary and secondary hydroxyl groups during polymerisation, and to the multiplicity of methyl side chains on the polymers.
- Conventional polymerisation of propylene glycol results in an atactic polymer.
- the isotactic polymers mainly exist in the laboratory. Mixtures of atactic and isotactic polymers may also occur.
- PPG has many properties in common with polyethylene glycol.
- Polypropylene glycols of all molecular weights are clear, viscous liquids with a low pour point, and which show an inverse temperature-solubility relationship, along with a rapid decrease in water solubility as the molecular weight increases.
- the terminal hydroxyl groups undergo the typical reactions of primary and secondary alcohols.
- the secondary hydroxyl group of polypropylene glycols is not as reactive as the primary hydroxyl group in polyethylene glycols.
- PPG is used in many formulations for polyurethanes.
- Polypropylene glycols used in the present invention are generally linear having molecular weights of 200 to 4000 g/mol, (generally 400 to 2000).
- the invention also provides a method of producing the linear polymer, which comprises melting and drying PEG or PPG, and the block copolymer, together with the difunctional compound at a temperature of 85°C to 100 0 C under vacuum; and then adding the difunctional isocyanate.
- block copolymers (b), based on propylene oxide and ethylene oxide can be initiated with ethylene glycol, glycerine, trimethylolethane, trimethylolpropane, pentaerythritol, sorbitol, sucrose and several other compounds. Mixed and alternating block copolymers can also be produced.
- block copolymers of PEG and PPG with terminal primary hydroxyl groups are yield. The primary hydroxyl groups are more reactive with isocyanates than secondary hydroxyl groups.
- PEG- PPG-PEG and PPG-PEG-PPG copolymers used in the present invention are generally linear having molecular weight of 200 to 14,000 g/mol.
- the block copolymer appears to contribute to the non-crystalline elastomeric nature of the polymer of the invention.
- the difunctional compound (c) is reactive with the difunctional isocyanate, and is typically a difunctional amine or diol.
- Diols in the range C 5 to C 20 preferably C 8 to Cj 5 are preferred. Thus, decanediol has been found to produce particularly good results.
- the diol may be a saturated or unsaturated diol. Branched diols may be used but straight chain diols are preferred.
- the two hydroxyl groups are generally on terminal carbon atoms.
- Preferred diols include 1,6-hexanediol, 1,10-decanediol, 1,12-dodecanediol and 1,16-hexadecanediol.
- the difunctional isocyanate (d) is generally one of the conventional diisocyanates, such as dicyclohexylmethane-4,4-diisocyanate, diphenylmethane-4,4- diisocyanate, 1 ,6-hexamethylene diisocyanate etc.
- the equivalent weight ratio of the components (a), (b), (c) and (d) is generally in the range 0.01-1 to 0.01-1 to 1 to 1.02-3 respectively. Of course, the skilled man through reasonable experimentation would determine the best ratio of ingredients to give the desired properties.
- the amount of component (d) is generally equal to the combined amounts of (a), (b) and (c) to provide the correct stoichiometry.
- the polymers are generally produced by melting and drying PEG or PPG, and PEG-PPG-PEG or PPG-PEG-PPG block copolymer together with the difunctional compound and a typical polyurethane catalyst (if used), e.g. ferric chloride, DABCO and/or tin (II) octoate, at a temperature of 85°C to 100°C (e.g. 95°C) under vacuum to remove excess moisture; before the diisocyanate, e.g. DMDI or HMDI is added thereto.
- the polymerisation is carried out in a batch or alternatively a continuous reactor; or the reaction mixture is fed into moulds and reacted for a specified time. After polymerisation the polymer is cooled down, pelletised or granulated and stored in a freezer for further analysis and processing.
- thermoplastic polyurethane elastomers of the invention are due to two factors: microphase separation of hard and soft blocks; and the semicrystalline nature of the polymer, whose amorphous phase has a low glass transition temperature.
- Hard blocks form from the difunctional compound and diisocyanate.
- Soft blocks are PEG, PPG or copolymer.
- the elasticity may depend on the ratio of hard to soft blocks and may be represented by Shore hardness measurements.
- the linear polymers of the present invention are soluble in certain organic solvents. This allows the polymer to be dissolved and the resultant solution cast to form films.
- the solution may also be employed for coating granules, tablets etc., in order to modify the polymer release properties. Alternatively, the solution can be poured into a non-solvent so as to precipitate polymer/active microparticles.
- the polymer can be ground, chopped, pelletised and melted by using conventional techniques used for processing thermoplastic polymers.
- the invention also provides a controlled release composition
- a controlled release composition comprising the linear polymer together with an active agent.
- Any type of plastic processing equipment e.g. extruder, injection moulding machine, compression moulding equipment and melt mixer can be used for mixing the polymer and active agent together and forming or reshape into any type of drug loaded device, e.g. a ring, pessary, patch, rod, spring or cone.
- the active agent may be a pharmaceutically active agent for human or animal use. It may also be any other agent where sustained release properties (e.g. algicides, fertilisers etc.) are required.
- the pharmaceutical solid dosage forms include suppositories, rings and pessaries for vaginal use, buccal inserts for oral administration, patches for transdermal administration etc. These dosage forms are generally administered to the patient, retained in place until delivery of active agent has occurred and the spent polymer is then removed.
- the polymer may also be used for implants, which remain in the body; or for coating such implants (
- the polymer of the present invention is an amphiphilic thermoplastic polymer and is thus suitable for the uptake of hydrophilic and hydrophobic, low and high molecular weight pharmaceutically active agents (up to and exceeding a molecular weight of 3000 e.g. up to 10,000, up to 50,000, up to 100,000 or even up to 200,000). Generally, the molecular weight of the active agent is in the range 200 to 20,000. A wide variety of water-soluble pharmaceutically active substances such as those listed in EPOO 16652 may thus be incorporated.
- the linear polymers of the present invention may be loaded with pharmaceutically active hydrophilic and hydrophobic agents, which are poorly water-soluble, provided that these can be dissolved in a common solvent with the polymer. The resultant solution can then be cast into any desired solid form.
- the linear polymers of the present invention may be extrusion loaded or melt mixed with pharmaceutically active agents, which are thermally stable at the polymer processing temperature.
- the release time of the present polymers may exceed 12 hrs, 24 hrs, 5 days, 10 days, 20 days or even 80 days for substantially complete release of available active agent.
- polyether polyol blends and copolymers used in the present invention are internal and melt rheology, softness and release rate modifiers. These types of low melting amphiphilic thermoplastic polyurethane polymers are particularly suitable for the melt loading of pharmaceutically active agent and melt processing of loaded polymer to pharmaceutical devices.
- compositions of particular interest include:
- Proteins e.g. interferon alpha, beta and gamma, insulin, human growth hormone, leuprolide; benzodiazepines e.g. midazolam; anti-migraine agents e.g. triptophans, ergotamine and its derivatives; anti-infective agents e.g. azoles, bacterial vaginosis, Candida; and ophthalmic agents e.g. latanoprost.
- interferon alpha, beta and gamma insulin, human growth hormone, leuprolide
- benzodiazepines e.g. midazolam
- anti-migraine agents e.g. triptophans, ergotamine and its derivatives
- anti-infective agents e.g. azoles, bacterial vaginosis, Candida
- ophthalmic agents e.g. latanoprost.
- active agent includes H 2 receptor antagonist, antimuscaririe, prostaglandin analogue, proton pump inhibitor, aminosalycilate, corticosteroid, chelating agent, cardiac glycoside, phosphodiesterase inhibitor, thiazide, diuretic, carbonic anhydrase inhibitor, antihypertensive, anti-cancer, anti-depressant, calcium channel blocker, analgesic, opioid antagonist, antiplatel, anticoagulant, fibrinolytic, statin, adrenoceptor agonist, beta blocker, antihistamine, respiratory stimulant, micolytic, expertorant, benzodiazepine, barbiturate, anxiolytic, antipsychotic, tricyclic anti depressant, 5HTi antagonist, opiate, 5HT, agonist, antiemetic, antiepileptic, dopaminergic, antibiotic, antifungal, anthelmintic, antiviral, antiprotozoal, antidiabetic, insulin, thyrotoxin
- Figure 1 shows molecular weight as a function of polymerisation time for certain polymers
- Figure 2 to 5 show various active agent release profiles.
- PEG400, PEG900, PEGlOOO and PEG2000 are polyethylene glycols having a molecular weight of 400, 900, 1000 and 2000 g/mol, respectively;
- PPGlOOO and PPG2000 are polypropylene glycols having a molecular weight of 1000 and 2000g/mol;
- PEG-PPG-PEGl 100 and PEG-PPG-PEG4400 are block copolymers having a molecular weight of 1100 and 4400 g/mol;
- PPG-PEG- PEG2000 is a block copolymer having a molecular weight of 2000 g/mol;
- DD is 1,10-decanediol and DDD is 1,12-dodecanediol;
- DMDI is dicyclohexylmethane-4,4- diisocyanate and HMDI is 1 ,6-hexamethylene diisocyanate;
- FeCl 3 is Ferric chloride
- DABCO M
- Polymers were produced by applying the polymerisation method described in WO patent Publication WO2004029125.
- the PEG, PPG, PEG-PPG-PEG and/or PPG-PEG-PPG were melted and vacuum dried at 95 °C along with the diol and the catalyst (if used) in a rotary-evaporator for an hour at a pressure below 1 mbar. At this point the dried mixture was fed into a reactor prior to the diisocyanate addition.
- the manufactured polymers are shown in Table 1.
- the polymerisations were performed as in Example 1 but the DMDI was replaced by HMDI for polymers F, G, H, I, K, L, M, N, O, P, Q and R in Table 1.
- the swelling determinations for a number of selected polymers were carried out in water, ethanol, isopropyl alcohol (IPA) and in a 50% mixture of IPA/water in order to measure the amount of solvent absorbed by the polymer.
- the results were calculated based on the average swelling of 10 specimens and are shown in Table 3.
- the formula used for the calculations is shown below:
- the manufactured polymers were tested for Shore hardness using durometers A and D.
- Durometers A and D are generally used to measure elasticity of soft and hard rubber, respectively. These measurements are well known to the skilled person in the field. The results are presented as the average of four measurements and are presented in Table 4.
- a number of selected polymers from Table 1 were dried over night under vacuum prior to the processing.
- the upper and lower plate temperatures of the compression moulding machine were set at the target processing temperature.
- Two Teflon sheets were placed between the mould and the hot plates.
- the melting time was 3-5 minutes followed by a 30 -120 seconds holding under pressure (170-200 bars).
- a predetermined amount of polymer was used to fill the mould.
- After cooling to room temperature the samples (pessary devices with dimensions 30mm x 10mm x lmm) were mechanically punched out and kept in the freezer for further analysis.
- the film processing conditions are shown in Table 5.
- Selected polymers were loaded with two different active compounds: fluconazole and oxybutynin.
- a 16mm co-rotating twin-screw laboratory extruder was used for loading the polymers.
- Table 6 shows the drug loading conditions.
- USP paddle technique is comprised of an automated UV dissolution system where a Distek (2100C model) dissolution paddle (speed 50rpm) is connected to a Unicam UV 500 spectrophotometer via an Icalis peristaltic pump. The system is operated using Dsolve software. In the incubator shaker method the samples were taken manually and the Unicam UV 500 spectrophotometer was used to analyse the samples.
- the fluconazole release profile obtained for Polymer A and Polymer C were compared with the release profiles obtained for a crosslinked and a linear high- swelling polyurethane polymer, see Figure 5.
- the diffusion loaded crosslinked polymer (crosslinked 17wt% fluconazole) was from patent EPOO 16652/EP0016654. While the linear high swelling polymer was from patent WO2004029125 and was loaded using diffusion (high %SW 17wt% fluconazole) as well as extrusion techniques (high %SW 20wt% fluconazole). The same dissolution method as in Example 10 was used to determine the release curves. These new polymers can provide an excellent control over drug release, see Figure 5.
Abstract
Description
Claims
Priority Applications (12)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2007800256285A CN101484495B (en) | 2006-07-08 | 2007-06-27 | Polyurethane elastomers |
CA2656788A CA2656788C (en) | 2006-07-08 | 2007-06-27 | Controlled release composition comprising polyurethane elastomers |
EP07733405A EP2038325B1 (en) | 2006-07-08 | 2007-06-27 | Polyurethane elastomers |
AT07733405T ATE498643T1 (en) | 2006-07-08 | 2007-06-27 | POLYURETHANE ELASTOMERS |
BRPI0713481A BRPI0713481B8 (en) | 2006-07-08 | 2007-06-27 | controlled release pharmaceutical composition in solid dosage form, linear polymer, and method for producing a linear polymer |
DK07733405.0T DK2038325T3 (en) | 2006-07-08 | 2007-06-27 | Polyurethane elastomers |
PL07733405T PL2038325T3 (en) | 2006-07-08 | 2007-06-27 | Polyurethane elastomers |
US12/373,002 US8361272B2 (en) | 2006-07-08 | 2007-06-27 | Polyurethane elastomers |
DE602007012545T DE602007012545D1 (en) | 2006-07-08 | 2007-06-27 | POLYURETHANE ELASTOMERS |
AU2007274119A AU2007274119B2 (en) | 2006-07-08 | 2007-06-27 | Polyurethane elastomers |
JP2009517399A JP5307710B2 (en) | 2006-07-08 | 2007-06-27 | Polyurethane elastomer |
US13/605,689 US8361273B2 (en) | 2006-07-08 | 2012-09-06 | Polyurethane elastomers |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB0613638.6 | 2006-07-08 | ||
GBGB0613638.6A GB0613638D0 (en) | 2006-07-08 | 2006-07-08 | Polyurethane elastomers |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/373,002 A-371-Of-International US8361272B2 (en) | 2006-07-08 | 2007-06-27 | Polyurethane elastomers |
US13/605,689 Continuation US8361273B2 (en) | 2006-07-08 | 2012-09-06 | Polyurethane elastomers |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2008007046A1 true WO2008007046A1 (en) | 2008-01-17 |
Family
ID=36926730
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/GB2007/002415 WO2008007046A1 (en) | 2006-07-08 | 2007-06-27 | Polyurethane elastomers |
Country Status (15)
Country | Link |
---|---|
US (2) | US8361272B2 (en) |
EP (1) | EP2038325B1 (en) |
JP (2) | JP5307710B2 (en) |
CN (1) | CN101484495B (en) |
AT (1) | ATE498643T1 (en) |
AU (1) | AU2007274119B2 (en) |
BR (1) | BRPI0713481B8 (en) |
CA (1) | CA2656788C (en) |
DE (1) | DE602007012545D1 (en) |
DK (1) | DK2038325T3 (en) |
ES (1) | ES2363704T3 (en) |
GB (1) | GB0613638D0 (en) |
PL (1) | PL2038325T3 (en) |
PT (1) | PT2038325E (en) |
WO (1) | WO2008007046A1 (en) |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2244782A2 (en) | 2008-01-25 | 2010-11-03 | The University of Utah Research Foundation | Linear order release polymer |
WO2011039418A1 (en) * | 2009-10-01 | 2011-04-07 | Bayer Schering Pharma Oy | An intrauterine system |
US8580294B2 (en) | 2010-10-19 | 2013-11-12 | International Partnership For Microbicides | Platinum-catalyzed intravaginal rings |
WO2015044415A1 (en) * | 2013-09-30 | 2015-04-02 | Universiteit Gent | Polyurethanes as oral drug delivery platform |
WO2015057505A1 (en) * | 2013-10-15 | 2015-04-23 | Lubrizol Advanced Materials, Inc. | Thermoplastic polyurethanes made with tin-free catalysts |
EP2826463A4 (en) * | 2012-03-13 | 2015-12-02 | Sumitomo Seika Chemicals | Cosmetic composition |
EP3017809A1 (en) | 2014-11-07 | 2016-05-11 | Ferring B.V. | Drug-device unit containing quinagolide |
US10137031B2 (en) | 2013-11-14 | 2018-11-27 | International Partnership For Microbicides, Inc. | Combination therapy intravaginal rings |
WO2023031218A1 (en) | 2021-08-31 | 2023-03-09 | Ferring B.V. | Diagnosis and treatment of ectopic endometriosis |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB0613333D0 (en) | 2006-07-05 | 2006-08-16 | Controlled Therapeutics Sct | Hydrophilic polyurethane compositions |
US8637629B2 (en) * | 2007-01-18 | 2014-01-28 | Lubrizol Advanced Materials, Inc. | High moisture vapor transmissive polyurethanes |
US20090233887A1 (en) * | 2008-03-12 | 2009-09-17 | Shalaby Shalaby W | Hydroswellable, Segmented, Aliphatic Polyurethanes and Polyurethane Ureas |
US8940799B2 (en) * | 2010-03-25 | 2015-01-27 | Medtronic Xomed, Inc. | Adjusting drug loading in polymeric materials |
CA2817713C (en) * | 2010-11-12 | 2018-12-04 | The University Of Utah Research Foundation | Intravaginal devices for controlled delivery of lubricants |
MX357598B (en) * | 2011-07-20 | 2018-07-16 | F Kiser Patrick | Intravaginal devices for drug delivery. |
JP5955922B2 (en) * | 2013-11-11 | 2016-07-20 | 三洋化成工業株式会社 | Polyurethane resin for water equivalent phantom materials |
CN105992783B (en) * | 2013-12-10 | 2019-09-24 | 路博润先进材料公司 | High resilience thermoplastic polyurethane |
CN107108837B (en) | 2014-10-31 | 2021-04-13 | 路博润先进材料公司 | Thermoplastic polyurethane films for delivering active agents to skin surfaces |
US11202986B2 (en) * | 2017-10-09 | 2021-12-21 | Ali Pournaghshband Isfahani | Plasticization-resistant polyurethane membrane and preparation method thereof |
TW201927846A (en) * | 2017-12-04 | 2019-07-16 | 日商住友精化股份有限公司 | Composition for emitting volatile substance |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1991002763A1 (en) * | 1989-08-15 | 1991-03-07 | British Technology Group Plc | Polymeric materials |
DE19842636A1 (en) * | 1997-09-24 | 1999-03-25 | Henkel Kgaa | Polyurethane adhesive bonding paper labels to polyolefin bottles |
WO2004029125A1 (en) * | 2002-09-27 | 2004-04-08 | Controlled Therapeutics (Scotland) Limited | Water-swellable polymers |
Family Cites Families (322)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SE505703C2 (en) | 1995-12-15 | 1997-09-29 | Polyrand Ab | Linear block polymer comprising urea and urethane groups, process for producing linear block polymers and use of the block polymers as implants |
US3916898A (en) | 1964-05-20 | 1975-11-04 | Searle & Co | Administration of medicaments and the like |
US3487068A (en) | 1966-12-16 | 1969-12-30 | Upjohn Co | Lincomycin-2-phosphates,7-substituted compounds and salts thereof |
US3830907A (en) | 1968-04-22 | 1974-08-20 | Searle & Co | Compositions for the sustained release of 17alpha-ethyl-19-nortestosterone |
US3565991A (en) | 1968-04-22 | 1971-02-23 | Searle & Co | Methods for use and compositions of 17alpha-ethyl-19-nortestosterone and carriers for the sustained release of steroids |
US3860701A (en) | 1968-04-22 | 1975-01-14 | Searle & Co | Method for use and compositions of 11-lower alkyl steroids and drug delivery system for the controlled elution of 11-lower alkyl steroids |
US3639157A (en) | 1968-07-18 | 1972-02-01 | Bayer Ag | Process for finishing textile materials with a polymer of a vinyl compound and the reaction product of a polyol and an organic polyisocyanate |
US3797494A (en) | 1969-04-01 | 1974-03-19 | Alza Corp | Bandage for the administration of drug by controlled metering through microporous materials |
US3854480A (en) | 1969-04-01 | 1974-12-17 | Alza Corp | Drug-delivery system |
US3734097A (en) | 1969-04-01 | 1973-05-22 | Alza Corp | Therapeutic adhesive tape |
US3598123A (en) | 1969-04-01 | 1971-08-10 | Alza Corp | Bandage for administering drugs |
US3948262A (en) | 1969-04-01 | 1976-04-06 | Alza Corporation | Novel drug delivery device |
US3993073A (en) | 1969-04-01 | 1976-11-23 | Alza Corporation | Novel drug delivery device |
US3896819A (en) | 1969-04-01 | 1975-07-29 | Alejandro Zaffaroni | IUD having a replenishing drug reservoir |
US3598122A (en) | 1969-04-01 | 1971-08-10 | Alza Corp | Bandage for administering drugs |
US3967618A (en) | 1969-04-01 | 1976-07-06 | Alza Corporation | Drug delivery device |
US3845761A (en) | 1970-06-02 | 1974-11-05 | Alza Corp | Intrauterine contraceptive anti-fertility device for the management of reproduction |
US3737521A (en) | 1970-12-09 | 1973-06-05 | Goodrich Co B F | Formulation for sustained release of a biological agent |
US4034756A (en) | 1971-01-13 | 1977-07-12 | Alza Corporation | Osmotically driven fluid dispenser |
US3760805A (en) | 1971-01-13 | 1973-09-25 | Alza Corp | Osmotic dispenser with collapsible supply container |
US3995631A (en) | 1971-01-13 | 1976-12-07 | Alza Corporation | Osmotic dispenser with means for dispensing active agent responsive to osmotic gradient |
US3941880A (en) | 1971-02-22 | 1976-03-02 | G. D. Searle & Co. | Method for use of 11-lower alkyl steroids |
US3731683A (en) | 1971-06-04 | 1973-05-08 | Alza Corp | Bandage for the controlled metering of topical drugs to the skin |
US3931113A (en) | 1971-06-21 | 1976-01-06 | Ppg Industries, Inc. | Impact-resistant thermoplastic polyester urethanes |
US4041208A (en) | 1971-06-21 | 1977-08-09 | Ppg Industries, Inc. | Transparent, impact-resistant polyesterurethane laminates |
US3881043A (en) | 1971-06-21 | 1975-04-29 | Ppg Industries Inc | Laminated safety windshields |
US3892842A (en) | 1971-09-01 | 1975-07-01 | Alza Corp | Intrauterine contraceptive device for releasing steroid having double bond functionality |
US3948254A (en) | 1971-11-08 | 1976-04-06 | Alza Corporation | Novel drug delivery device |
US3845770A (en) | 1972-06-05 | 1974-11-05 | Alza Corp | Osmatic dispensing device for releasing beneficial agent |
US3921636A (en) | 1973-01-15 | 1975-11-25 | Alza Corp | Novel drug delivery device |
US3867933A (en) | 1973-03-06 | 1975-02-25 | Tecna Corp | Intrauterine device and process of making the same |
US3916899A (en) | 1973-04-25 | 1975-11-04 | Alza Corp | Osmotic dispensing device with maximum and minimum sizes for the passageway |
US4036227A (en) | 1973-04-25 | 1977-07-19 | Alza Corporation | Osmotic releasing device having a plurality of release rate patterns |
FR2250520B1 (en) | 1973-11-09 | 1977-04-15 | Cournut Rene | |
US3901852A (en) | 1974-07-29 | 1975-08-26 | Upjohn Co | Thermoplastic polyurethanes prepared from 4,4'-methylenebis (phenyl isocyanate) |
US3993072A (en) | 1974-08-28 | 1976-11-23 | Alza Corporation | Microporous drug delivery device |
US4096238A (en) | 1974-12-23 | 1978-06-20 | Alza Corporation | Method for administering drug to the gastrointestinal tract |
US4018918A (en) | 1975-05-20 | 1977-04-19 | The Upjohn Company | Topical clindamycin preparations |
GB1479987A (en) | 1975-06-20 | 1977-07-13 | Interox Chemicals Ltd | Polyurethanes |
GB1551620A (en) | 1976-12-13 | 1979-08-30 | Ici Ltd | Delivery means for biologically active agents |
US4235988A (en) | 1976-12-13 | 1980-11-25 | Imperial Chemical Industries Limited | Delivery means for biologically active agents |
US4289757A (en) | 1978-02-28 | 1981-09-15 | The Upjohn Company | Method for treating inflammation |
US4205115A (en) | 1978-04-19 | 1980-05-27 | Ppg Industries, Inc. | Polyester coating composition |
US4215691A (en) | 1978-10-11 | 1980-08-05 | Alza Corporation | Vaginal contraceptive system made from block copolymer |
US4286587A (en) | 1978-10-11 | 1981-09-01 | Alza Corporation | Vaginal drug delivery system made from polymer |
US4237885A (en) | 1978-10-23 | 1980-12-09 | Alza Corporation | Delivery system with mated members for storing and releasing a plurality of beneficial agents |
US5017382A (en) | 1979-03-21 | 1991-05-21 | National Research Development Corporation | Controlled release compositions (II) |
US5079009A (en) | 1979-03-21 | 1992-01-07 | National Research Development Corporation | Controlled release compositions including polyethylene oxide with urethane cross-linking |
AU537741B2 (en) | 1979-03-21 | 1984-07-12 | British Technology Group Limited | Controlled release compositions |
US4250611A (en) | 1979-04-19 | 1981-02-17 | Alza Corporation | Process for making drug delivery device with reservoir |
US4264757A (en) | 1979-06-26 | 1981-04-28 | Union Carbide Corporation | Radiation-curable allyl- or vinyl capped polycaprolactone compositions |
US4402695A (en) | 1980-01-21 | 1983-09-06 | Alza Corporation | Device for delivering agent in vagina |
US4731289A (en) | 1980-02-14 | 1988-03-15 | Ppg Industries, Inc. | Abrasion resistant polyurethane coatings for rigid plastics |
US4276405A (en) | 1980-03-28 | 1981-06-30 | Union Carbide Corporation | Low-energy-curable coatings compositions |
DE3017989C2 (en) | 1980-05-10 | 1982-05-19 | IPOS Gesellschaft für integrierte Prothesen-Entwicklung und orthopädietechnischen Service mbH & Co KG, 2120 Lüneburg | "Collection bag for artificial intestinal exits" |
AU558611B2 (en) | 1981-02-03 | 1987-02-05 | Bayer Aktiengesellschaft | Polyurethane gel |
US4466936A (en) | 1981-02-03 | 1984-08-21 | Bayer Aktiengesellschaft | Production of molds using gel compositions with depot action based on a polyurethane matrix and relatively high molecular weight polyols |
JPS57155230A (en) | 1981-02-27 | 1982-09-25 | Daicel Chem Ind Ltd | Lactone polymer having narrow molecular weight distribution and its preparation |
JPS57185313A (en) | 1981-05-08 | 1982-11-15 | Daicel Chem Ind Ltd | Polyurethane and its preparation |
US4426485A (en) | 1982-06-14 | 1984-01-17 | Union Carbide Corporation | Polymers with hydrophobe bunches |
JPS5948409A (en) | 1982-09-10 | 1984-03-19 | Teikoku Seiyaku Kk | Promotor for orthodontic tooth mobility |
US4438225A (en) | 1983-04-12 | 1984-03-20 | Henkel Corporation | Polyester polyols from bishydroxymethyl tricyclo compounds and caprolactone and polyurethanes based thereon |
GB8319766D0 (en) | 1983-07-22 | 1983-08-24 | Graham N B | Controlled release device |
FR2557576B1 (en) | 1984-01-03 | 1988-06-03 | Gould Francis | HYDROPHILIC POLYURETHANE ACRYLATE COMPOSITION, PREPARATION METHOD AND USE THEREOF AS BURNAGE DRESSING, IMPLANT, CONTRACEPTIVE, INTRA-UTERINE DEVICE, CANNULA, ORAL APPLICATION SYSTEM, GAS PERMEABLE MEMBRANE, CORNEAL PROSTHESIS, DRESSING DIALYSIS MEMBRANE, CONTACT LENS AND COATING OF SHIPS |
US4694238A (en) | 1984-01-10 | 1987-09-15 | Peter Norton | Dual voltage power supply system for vehicles |
GB8403138D0 (en) | 1984-02-07 | 1984-03-14 | Graham N B | Sustained release of active ingredient |
US4503216A (en) | 1984-02-21 | 1985-03-05 | Eastman Kodak Company | Hydroxyl-terminated polyether-esters |
US4568741A (en) | 1984-05-15 | 1986-02-04 | The Upjohn Company | Synthesis of 7-halo-7-deoxylincomycins |
US4596576A (en) | 1984-10-12 | 1986-06-24 | Akzo N.V. | Release system for two or more active substances |
IE58110B1 (en) | 1984-10-30 | 1993-07-14 | Elan Corp Plc | Controlled release powder and process for its preparation |
JPS61250019A (en) | 1985-04-27 | 1986-11-07 | Bridgestone Corp | Production of fine foam of polyurethane elastomer |
JPS6257467A (en) | 1985-09-06 | 1987-03-13 | Asahi Glass Co Ltd | Coating agent composition |
US4707495A (en) | 1985-10-28 | 1987-11-17 | Ortho Pharmaceutical | Peptic ulcer treatment method |
US5731303A (en) | 1985-12-04 | 1998-03-24 | Conrex Pharmaceutical Corporation | Transdermal and trans-membrane delivery compositions |
US5023252A (en) | 1985-12-04 | 1991-06-11 | Conrex Pharmaceutical Corporation | Transdermal and trans-membrane delivery of drugs |
US4917686A (en) | 1985-12-16 | 1990-04-17 | Colorado Biomedical, Inc. | Antimicrobial device and method |
IE59361B1 (en) | 1986-01-24 | 1994-02-09 | Akzo Nv | Pharmaceutical preparation for obtaining a highly viscous hydrogel or suspension |
US5219885A (en) | 1987-02-16 | 1993-06-15 | Froelich Juergen | Prostaglandin E1 derivatives as pharmaceutically active agents, and pharmaceutical compositions containing these compounds, especially for transcutaneous administration |
US4804691A (en) | 1987-08-28 | 1989-02-14 | Richards Medical Company | Method for making a biodegradable adhesive for soft living tissue |
EP0310037B1 (en) | 1987-09-28 | 1993-07-14 | Kuraray Co., Ltd. | Leather-like sheet material and method of producing same |
US5035891A (en) | 1987-10-05 | 1991-07-30 | Syntex (U.S.A.) Inc. | Controlled release subcutaneous implant |
JP2538953B2 (en) | 1987-11-17 | 1996-10-02 | 三菱重工業株式会社 | Balance mechanism of industrial robot |
IE60383B1 (en) | 1988-05-27 | 1994-07-13 | Elan Corp Plc | Controlled release pharmaceutical formulation |
US5219663A (en) | 1988-06-22 | 1993-06-15 | Hitachi Maxell, Ltd. | Magnetic recording medium having a magnetic layer formed from an aromatic polycarbonate polyurethane resin |
JPH024736A (en) | 1988-06-22 | 1990-01-09 | Hitachi Maxell Ltd | Polycarbonate polyol, aromatic polycarbonate polyurethane resin, coating material, cast film and magnetic recording medium |
JP2613441B2 (en) | 1988-07-18 | 1997-05-28 | トヨタ自動車株式会社 | Manufacturing method of foamed polyurethane |
US5000955A (en) | 1988-07-29 | 1991-03-19 | Tyndale Plains-Hunter Ltd. | Thermally reversible polyurethane hydrogels and cosmetic, biological and medical uses |
US4933418A (en) | 1988-08-10 | 1990-06-12 | Ormco Corporation | Stain-resistant orthodontic device |
US4895934A (en) | 1988-08-22 | 1990-01-23 | E. I. Du Pont De Nemours And Company | Process for the preparation of clindamycin phosphate |
SE463851B (en) | 1988-09-02 | 1991-02-04 | Amsu Ltd | COMPOSITION FOR TREATMENT OF ERECT DYSFUNCTION THROUGH URETRA |
US5470829A (en) | 1988-11-17 | 1995-11-28 | Prisell; Per | Pharmaceutical preparation |
FR2641786B1 (en) | 1989-01-19 | 1992-09-11 | Sami | URETHANE POLYMER COMPOSITION AND PREPARATION OF ARTICLES THEREFROM |
DE3903538A1 (en) | 1989-02-07 | 1990-08-16 | Basf Ag | PRODUCTION OF EMULSIFIER-FREE, AQUEOUS POLYURETHANE DISPERSIONS |
ES2010145A6 (en) | 1989-03-02 | 1989-10-16 | Uriach & Cia Sa J | 2-picolylamine derivates. |
US5888930A (en) | 1989-03-27 | 1999-03-30 | Bend Research, Inc. | Asymmetric microporous beads for controlled release |
US5002540A (en) | 1989-05-22 | 1991-03-26 | Warren Kirschbaum | Intravaginal device and method for delivering a medicament |
US5034461A (en) | 1989-06-07 | 1991-07-23 | Bausch & Lomb Incorporated | Novel prepolymers useful in biomedical devices |
US5061254A (en) | 1989-06-21 | 1991-10-29 | Becton, Dickinson And Company | Thermoplastic elastomeric hydrophilic polyetherurethane expandable catheter |
US5110598A (en) | 1989-06-30 | 1992-05-05 | Smithkline Beecham Corp. | Intermittent release dosage form |
US5178874A (en) | 1989-06-30 | 1993-01-12 | Smithkline Beechman Corporation | Intermittent release dosage form |
JP2844474B2 (en) | 1989-07-19 | 1999-01-06 | ダイセル化学工業株式会社 | Method for producing polyurethane |
US5118779A (en) | 1989-10-10 | 1992-06-02 | Polymedica Industries, Inc. | Hydrophilic polyurethane elastomers |
DE4006521A1 (en) | 1990-03-02 | 1991-09-05 | Bayer Ag | SUGAR-BASED POLYMERS FOR COATING AND EMBEDDING MEDICINAL SUBSTANCES |
DE4019171A1 (en) | 1990-06-15 | 1991-12-19 | Henkel Kgaa | COATING AGENT |
GB2244920B (en) | 1990-06-16 | 1994-05-25 | British Aerospace | A contraceptive device |
US5130126A (en) | 1990-07-09 | 1992-07-14 | Nippon Oil & Fats Co., Ltd. | Polymer-drug conjugate and a method of producing it |
DK0540580T3 (en) | 1990-07-26 | 1994-05-16 | Monsanto Co | Polymeric drug delivery system |
US5326632A (en) | 1990-08-07 | 1994-07-05 | Komatsu Seiren Co., Ltd. | Moisture-permeable waterproof fabric and process for production thereof |
US5114718A (en) | 1990-09-20 | 1992-05-19 | The Procter & Gamble Company | Sustained release compositions for treating periodontol disease |
JPH05239205A (en) | 1991-02-13 | 1993-09-17 | Ajinomoto Co Inc | Poly(amino acid-urethane) resin |
GB2254002B (en) | 1991-01-16 | 1995-03-22 | Controlled Therapeutics | Retrievable pessary |
US5652274A (en) | 1991-03-01 | 1997-07-29 | Martin; Alain | Therapeutic-wound healing compositions and methods for preparing and using same |
US5159047A (en) | 1991-06-14 | 1992-10-27 | E. I. Du Pont De Nemours And Company | Coatings containing caprolactone oligomer polyols |
CA2071137A1 (en) | 1991-07-10 | 1993-01-11 | Clarence C. Lee | Composition and method for revitalizing scar tissue |
US5176907A (en) | 1991-08-13 | 1993-01-05 | The Johns Hopkins University School Of Medicine | Biocompatible and biodegradable poly (phosphoester-urethanes) |
US5322063A (en) | 1991-10-04 | 1994-06-21 | Eli Lilly And Company | Hydrophilic polyurethane membranes for electrochemical glucose sensors |
US5252602A (en) | 1991-10-11 | 1993-10-12 | Rafeul Alam | Effects of misoprostol on allergic responses |
ES2114569T3 (en) | 1991-10-16 | 1998-06-01 | Richardson Vicks Inc | IMPROVED SKIN PENETRATION SYSTEM FOR THE IMPROVED TOPICAL ADMINISTRATION OF PHARMACES. |
US6117843A (en) | 1992-02-18 | 2000-09-12 | Lloyd J. Baroody | Compositions for the treatment of acne containing clindamycin and benzoyl peroxide |
US5650171A (en) | 1992-04-29 | 1997-07-22 | Penederm, Inc. | Retinoic acid-containing polyether-polyurethane compositions |
US5578643A (en) | 1992-05-20 | 1996-11-26 | Loyola University Of Chicago | Protective prostaglandins for use in conjunction with chemotherapeutic agents |
JP3119533B2 (en) | 1992-05-27 | 2000-12-25 | 日本ペイント株式会社 | Chipping resistant coating composition |
US5710215A (en) | 1992-06-15 | 1998-01-20 | Ebnother Ag | Method and material mixture for manufacture of reactive hotmelts |
US5310759A (en) | 1992-08-12 | 1994-05-10 | Bockman Richard S | Methods of protecting and preserving connective and support tissues |
US6328991B1 (en) | 1992-10-21 | 2001-12-11 | John Myhling | Composition and method for prevention of sexually transmitted diseases, including aids |
DE69332954D1 (en) | 1992-10-21 | 2003-06-12 | Gynetech Lab Inc | DISPENSING SYSTEM CONSISTING OF A VAGINASCHWAMM |
US5747582A (en) | 1992-10-29 | 1998-05-05 | Bayer Aktiengesellschaft | Aqueous coating compositions and their use for the preparation of coatings that are permeable to water vapor |
DE4241118A1 (en) | 1992-12-07 | 1994-06-09 | Basf Ag | Use of cationic polyurethanes and polyureas as auxiliaries in cosmetic and pharmaceutical preparations |
DE4242687B8 (en) | 1992-12-17 | 2006-01-12 | Henkel Kgaa | Hydrophilic polyurethanes |
DE4315173A1 (en) | 1992-12-23 | 1994-06-30 | Bayer Ag | Pure, especially catalyst-free polyurethanes |
US5324746A (en) | 1993-02-12 | 1994-06-28 | Mckee Rex N | Method of treating damaged mucosal and epithelial tissues with misoprostol |
GB9306887D0 (en) * | 1993-04-01 | 1993-05-26 | Graham Neil B | Random block copolymers |
US5328954A (en) | 1993-04-16 | 1994-07-12 | Icet, Inc. | Encrusting and bacterial resistant coatings for medical applications |
FR2705567A1 (en) | 1993-05-25 | 1994-12-02 | Smith & Nephew Laboratoires Fi | Microparticles, preparation process and application to dressings |
US5854385A (en) | 1995-10-06 | 1998-12-29 | Basf Corporation | Coating compositions with low molecular weight carbamate or urea component |
US6160058A (en) | 1993-07-28 | 2000-12-12 | Basf Corporation | Curable coating compositions containing blends of carbamate-functional compounds |
US5994479A (en) | 1993-07-28 | 1999-11-30 | Basf Corporation | Curable coating compositions containing blends of carbamate-functional compounds |
US5726244A (en) | 1995-08-10 | 1998-03-10 | Basf Corporation | Aqueous coating compositions for environmental etch resistant coatings |
US6084038A (en) | 1993-07-28 | 2000-07-04 | Basf Corporation | Curable coating compositions containing blends of carbamate-functional compounds |
US5777048A (en) | 1996-06-20 | 1998-07-07 | Basf Corporation | Method for modified aminoplast compounds, aminoplasts obtained thereby and coatings containing the same |
US5827930A (en) | 1995-10-06 | 1998-10-27 | Basf Corporation | Curable coating composition |
US5744550A (en) | 1994-11-03 | 1998-04-28 | Basf Corporation | Curable coating compositions containing carbamate additives |
US5792810A (en) | 1995-10-06 | 1998-08-11 | Basf Corporation | Curable coating composition including compound having carbamate and hydroxyl functionality |
US6080825A (en) | 1993-07-28 | 2000-06-27 | Basf Corporation | Curable coating compositions containing blends of carbamate-functional compounds |
US6423788B1 (en) | 1995-10-06 | 2002-07-23 | Basf Corporation | Curable coating composition |
DE69405939T2 (en) | 1993-07-28 | 1998-05-07 | Basf Corp | Curable polyureas |
US5770650A (en) | 1995-10-06 | 1998-06-23 | Basf Corporation | Curable compositions for coatings |
JPH0753663A (en) * | 1993-07-30 | 1995-02-28 | Takiron Co Ltd | Base polymer for percutaneous absorption preparation |
US5514698A (en) | 1994-03-21 | 1996-05-07 | Ortho Pharmaceutical Corporation | Antifungal vaginal cream composition |
US5472785A (en) | 1994-04-12 | 1995-12-05 | Minnesota Mining And Manufacturing Company | Reactive wax-containing moisture curable hot melt composition |
US5985859A (en) | 1994-04-14 | 1999-11-16 | The University Of Alabama | Methods of inhibiting bacterial sialidase |
IL109539A0 (en) | 1994-05-03 | 1994-08-26 | Yissum Res Dev Co | Substained-release pharmaceutical system for the delivery of antioxidants |
PT797604E (en) | 1994-05-25 | 2000-05-31 | Henkel Kgaa | POLYURETHANE FUSING TAIL THAT STRESSES THROUGH HUMIDITY ACTION |
US5681278A (en) | 1994-06-23 | 1997-10-28 | Cormedics Corp. | Coronary vasculature treatment method |
GB9419566D0 (en) | 1994-09-27 | 1994-11-16 | El Refaey Hazem | Oral prostagladins for the routine management of the third stage of labour |
IL116433A (en) | 1994-12-19 | 2002-02-10 | Galen Chemicals Ltd | INTRAVAGINAL DRUG DELIVERY DEVICES FOR THE ADMINISTRATION OF 17β-OESTRADIOL PRECURSORS |
US5659003A (en) | 1994-12-21 | 1997-08-19 | Basf Corporation | Polyurethane polymer or oligomer having carbamate groups, method for its preparation, and coating composition |
US20030158369A1 (en) | 1995-02-02 | 2003-08-21 | Slagel Edwin C. | Impact resistant polyurethane and method of manufacture thereof |
GB9506946D0 (en) | 1995-04-04 | 1995-05-24 | Univ Strathclyde | Microgels |
RU2189380C2 (en) | 1995-05-26 | 2002-09-20 | Хенкель КГАА | Water free or low water, partially crystalline, solid at room temperature glue (versions) |
CA2222811C (en) | 1995-06-01 | 2008-09-30 | G.D. Searle & Co. | Stabilized solid dispersions of misoprostol |
US7833543B2 (en) | 1995-06-07 | 2010-11-16 | Durect Corporation | High viscosity liquid controlled delivery system and medical or surgical device |
US5733538A (en) | 1995-06-07 | 1998-03-31 | Thoratec Laboratories, Inc. | Surface-modifying copolymers having cell adhesion properties |
US5968542A (en) | 1995-06-07 | 1999-10-19 | Southern Biosystems, Inc. | High viscosity liquid controlled delivery system as a device |
US5747058A (en) | 1995-06-07 | 1998-05-05 | Southern Biosystems, Inc. | High viscosity liquid controlled delivery system |
US6413536B1 (en) | 1995-06-07 | 2002-07-02 | Southern Biosystems, Inc. | High viscosity liquid controlled delivery system and medical or surgical device |
US5900433A (en) | 1995-06-23 | 1999-05-04 | Cormedics Corp. | Vascular treatment method and apparatus |
US5948416A (en) | 1995-06-29 | 1999-09-07 | The Procter & Gamble Company | Stable topical compositions |
JPH11510837A (en) | 1995-07-28 | 1999-09-21 | フォーカル,インコーポレイテッド | Multi-block biodegradable hydrogels for use as controlled release and tissue treatment agents for drug delivery |
KR19990044445A (en) | 1995-09-13 | 1999-06-25 | 니뽄 신야쿠 가부시키가이샤 | PPE1-containing lyophilized preparation and its preparation |
DE19541658A1 (en) | 1995-11-08 | 1997-05-15 | Basf Ag | Water-soluble or water-dispersible graft polymers, their preparation and their use |
US6103852A (en) | 1995-12-01 | 2000-08-15 | Hokushin Corporation | Method for preparing amorphous polymer chains in elastomers |
US6008312A (en) | 1995-12-01 | 1999-12-28 | Hokushin Corp | Method for producing millable polyurethanes and polyurethane elastomers |
EP0869772B1 (en) | 1995-12-27 | 2001-10-04 | Janssen Pharmaceutica N.V. | Bioadhesive solid dosage form |
US6521164B1 (en) | 1996-02-06 | 2003-02-18 | Parker-Hannifin Corporation | Injection-moldable thermoplastic polyurethane elastomer |
US5627254A (en) | 1996-05-03 | 1997-05-06 | The Dow Chemical Company | Rigid thermoplastic plyurethane comprising units of butane diol and a polyethylene glycol |
US5817343A (en) | 1996-05-14 | 1998-10-06 | Alkermes, Inc. | Method for fabricating polymer-based controlled-release devices |
MXPA98001339A (en) | 1996-07-01 | 2004-10-07 | Basf Corp | Curable coating compositions containing carbamate additives. |
US5972372A (en) | 1996-07-31 | 1999-10-26 | The Population Council, Inc. | Intravaginal rings with insertable drug-containing core |
US6043224A (en) | 1996-09-05 | 2000-03-28 | The Massachusetts Institute Of Technology | Compositions and methods for treatment of neurological disorders and neurodegenerative diseases |
US6184248B1 (en) | 1996-09-05 | 2001-02-06 | Robert K. K. Lee | Compositions and methods for treatment of neurological disorders and neurodegenerative diseases |
US6130309A (en) | 1996-09-20 | 2000-10-10 | Tyndale Plains-Hunter, Ltd. | Hydrophilic polyether polyurethanes containing carboxylic acid |
DE19638570A1 (en) * | 1996-09-20 | 1998-03-26 | Bayer Ag | Active ingredient-containing thermoplastic polyurethanes |
DE69702926T2 (en) | 1996-11-04 | 2001-02-22 | Huntsman Ici Chem Llc | POLYURETHANE FOAM |
ES2158611T3 (en) | 1996-12-20 | 2001-09-01 | Alza Corp | COMPOSITION IN INJECTABLE GEL WITH RETARD EFFECT AND PROCEDURE FOR THE PREPARATION OF SUCH COMPOSITION. |
US5853767A (en) | 1997-01-02 | 1998-12-29 | Melman; Steven A. | Compositions for treating fungal, parasitic and/or bacterial infections, especially infections of organs such as the skin and vagina |
US20050208152A1 (en) | 1997-01-22 | 2005-09-22 | Marton Milankovits | Pharmaceutical compositions primarily for the treatment and prevention of genitourinary infections and their extragenital complications |
WO1998044952A1 (en) | 1997-04-04 | 1998-10-15 | Monsanto Company | pH-SELECTIVE DELIVERY SYSTEM USING CROSS-LINKED POLYMERIC RESINS AS VEHICLES |
US20020115814A1 (en) | 1997-04-28 | 2002-08-22 | Woodhouse Kimberly Ann | Incorporation by reference of co-pending application |
US6221997B1 (en) | 1997-04-28 | 2001-04-24 | Kimberly Ann Woodhouse | Biodegradable polyurethanes |
GR1002847B (en) | 1997-05-06 | 1998-01-27 | Use of micropostol and/or micropostol acid for the preparation of a medicine for the therapeutic treatiment of problems related to the erection | |
JPH10332902A (en) | 1997-05-27 | 1998-12-18 | Nippon Ee R C Kk | Plastic lens, its production and primer composition |
US6572874B1 (en) | 1998-05-15 | 2003-06-03 | Umd, Inc. | Vaginal delivery of bisphosphonates |
US6197327B1 (en) | 1997-06-11 | 2001-03-06 | Umd, Inc. | Device and method for treatment of dysmenorrhea |
US6416779B1 (en) | 1997-06-11 | 2002-07-09 | Umd, Inc. | Device and method for intravaginal or transvaginal treatment of fungal, bacterial, viral or parasitic infections |
ES2123466B1 (en) | 1997-06-11 | 1999-11-16 | Merquinsa Mercados Quimicos S | THERMOPLASTIC OF POLYURETHANE AND PROCEDURE FOR ITS OBTAINING. |
US6039968A (en) | 1997-06-24 | 2000-03-21 | Hoechst Marion Roussel | Intravaginal drug delivery device |
US6103765A (en) | 1997-07-09 | 2000-08-15 | Androsolutions, Inc. | Methods for treating male erectile dysfunction |
AU742787B2 (en) | 1997-07-09 | 2002-01-10 | Androsolutions, Inc. | Improved methods and compositions for treating male erectile dysfunction |
JP2001514279A (en) | 1997-08-25 | 2001-09-11 | ユニオン・カーバイド・ケミカルズ・アンド・プラスティックス・テクノロジー・コーポレイション | Biodegradable lactone copolymer |
DE19737348C2 (en) | 1997-08-27 | 2002-07-25 | Dan-Gabriel Vulpescu | Pharmaceutical composition containing clindamycin and clotrimazole |
DE19742217A1 (en) | 1997-09-24 | 1999-04-01 | Henkel Kgaa | Polyurethane for thermally removable label adhesive |
DE19744473A1 (en) | 1997-10-09 | 1999-04-15 | Basf Ag | Use of water-soluble or water-dispersible polyurethanes as coating agents or binders for pharmaceutical dosage forms |
US20020004529A1 (en) | 1997-10-20 | 2002-01-10 | Gary W. Neal | Methods, compositions, and kits for enhancing female sexual desire and responsiveness |
US6593369B2 (en) | 1997-10-20 | 2003-07-15 | Vivus, Inc. | Methods, compositions, and kits for enhancing female sexual desire and responsiveness |
US5877216A (en) | 1997-10-28 | 1999-03-02 | Vivus, Incorporated | Treatment of female sexual dysfunction |
US20040044080A1 (en) | 1997-10-28 | 2004-03-04 | Place Virgil A. | Treatment of dyspareunia with topically administered nitroglycerin formulations |
US20020099003A1 (en) | 1997-10-28 | 2002-07-25 | Wilson Leland F. | Treatment of female sexual dysfunction with vasoactive agents, particularly vasoactive intestinal polypeptide and agonists thereof |
CA2306837C (en) | 1997-10-28 | 2007-05-08 | Asivi, Llc. | Treatment of female sexual dysfunction |
US20050070516A1 (en) | 1997-10-28 | 2005-03-31 | Vivus Inc. | As-needed administration of an androgenic agent to enhance female desire and responsiveness |
US20020013304A1 (en) | 1997-10-28 | 2002-01-31 | Wilson Leland F. | As-needed administration of an androgenic agent to enhance female sexual desire and responsiveness |
US20040014761A1 (en) | 1997-10-28 | 2004-01-22 | Place Virgil A. | Treatment of female sexual dysfunction with phosphodiesterase inhibitors |
US6414028B1 (en) | 1997-11-05 | 2002-07-02 | Nexmed Holdings, Inc. | Topical compositions containing prostaglandin E1 |
US6046244A (en) | 1997-11-05 | 2000-04-04 | Nexmed Holdings, Inc. | Topical compositions for prostaglandin E1 delivery |
BR9815099A (en) | 1997-11-17 | 2000-10-10 | Cosma Int Inc | Manufacturing process of a spacer assembly, spacer, and truck bed. |
ES2138918B1 (en) | 1997-11-20 | 2000-09-16 | Merquinsa Mercados Quimicos S | THERMOPLASTIC OF CRYSTALLINE POLYURETHANE AND METHOD FOR ITS OBTAINING. |
US6022554A (en) | 1997-12-15 | 2000-02-08 | American Home Products Corporation | Polymeric microporous film coated subcutaneous implant |
DE19757569A1 (en) | 1997-12-23 | 1999-06-24 | Bayer Ag | Thermoplastic polyurethane molding composition giving little condensate, for surface cladding on vehicles |
US5959775A (en) | 1997-12-23 | 1999-09-28 | 3M Innovative Properties Company | Urethane/acrylate bead bond for retroreflective articles |
CA2319197A1 (en) * | 1998-01-28 | 1999-08-05 | Bristol-Myers Squibb Company | Methods of preparing polyurethane adhesives, adhesives produced thereby and medical devices employing the same |
US6028057A (en) | 1998-02-19 | 2000-02-22 | Thorn Bioscience, Llc | Regulation of estrus and ovulation in gilts |
BRPI9908893B8 (en) | 1998-03-19 | 2021-05-25 | Merck & Co Inc | liquid polymeric composition for the controlled release of hydrophobic bioactive substances. |
US5891915A (en) | 1998-05-01 | 1999-04-06 | Wysor; Michael S. | Method for enhancing female sexual response and an ointment therefor |
US6031002A (en) | 1998-05-01 | 2000-02-29 | Michael Ebert | Method for enhancing female sexual response and a composition therefor |
US6013637A (en) | 1998-06-12 | 2000-01-11 | Dermik Laboratories Inc. | Anti-acne method and composition |
US5942545A (en) | 1998-06-15 | 1999-08-24 | Macrochem Corporation | Composition and method for treating penile erectile dysfunction |
DE19847791A1 (en) | 1998-10-16 | 2000-04-20 | Bayer Ag | Aqueous polyurethane dispersions |
NL1010367C2 (en) | 1998-10-21 | 2000-04-25 | Akzo Nobel Nv | Water vapor permeable thermoplastic polyurethane film. |
DE19849499A1 (en) | 1998-10-27 | 2000-05-04 | Basf Ag | Process for the complete drying of hydrogels |
GB9826192D0 (en) | 1998-12-01 | 1999-01-20 | Controlled Theraputics Scotlan | Oral transmucosal delivery |
US20050004226A1 (en) | 1998-12-10 | 2005-01-06 | Nexmed (Holdings), Inc. | Compositions and methods for amelioration of human female sexual dysfunction |
US6486207B2 (en) | 1998-12-10 | 2002-11-26 | Nexmed (Holdings), Inc. | Compositions and methods for amelioration of human female sexual dysfunction |
US6825234B2 (en) | 1998-12-10 | 2004-11-30 | Nexmed (Holdings) , Inc. | Compositions and methods for amelioration of human female sexual dysfunction |
DE10004723A1 (en) | 2000-02-03 | 2001-08-09 | Bayer Ag | Aqueous barrier layer based on polyurethane dispersions |
US6545119B2 (en) | 1999-03-08 | 2003-04-08 | Toyo Boseki Kabushiki Kaisha | Magnetic recording media and thermoplastic polyurethane resins therefor |
ES2244422T3 (en) | 1999-04-01 | 2005-12-16 | Alza Corporation | DEVICES FOR THE TRANSDERMAL ADMINISTRATION OF PHARMACOS THAT INCLUDE A POLYURETHANE DEPOSIT FOR PHARMACOS. |
DE19915932A1 (en) | 1999-04-09 | 2000-10-19 | Freudenberg Carl Fa | Thermoplastic processable polyurethane molding compound |
US6607686B2 (en) | 1999-04-20 | 2003-08-19 | Callaway Golf Company | Thermosetting polyurethane material for a golf ball |
US6592472B2 (en) | 1999-04-20 | 2003-07-15 | Callaway Golf Company | Golf ball having a non-yellowing cover |
US6117024A (en) | 1999-04-20 | 2000-09-12 | Callaway Golf Company | Golf ball with polyurethane cover |
IT1312310B1 (en) | 1999-05-07 | 2002-04-15 | Recordati Ind Chimica E Farma | USE OF SELECTIVE 1B ADRENERGIC RECEPTOR ANTAGONISTS TO IMPROVE SEXUAL DYSFUNCTION |
TWI232111B (en) | 1999-08-06 | 2005-05-11 | Upjohn Co | Intravaginal clindamycin ovule composition |
US6642274B1 (en) | 1999-09-09 | 2003-11-04 | Gary W. Neal | Methods and compositions for preventing and treating prostate disorders |
US6323241B1 (en) | 2000-01-10 | 2001-11-27 | Nexmed (Holdings) Inc. | Prostaglandin compositions and methods of treatment for male erectile dysfunction |
US20040110843A1 (en) | 2000-01-10 | 2004-06-10 | Nexmed (Holdings), Inc. | Methods of treatment of male erectile dysfunction |
US7105571B2 (en) | 2000-01-10 | 2006-09-12 | Nexmed Holdings, Inc. | Prostaglandin compositions and methods of treatment for male erectile dysfunction |
US6693135B2 (en) | 2000-01-10 | 2004-02-17 | Nexmed (Holdings) Incorporated | Prostaglandin compositions and methods of treatment for male erectile dysfunction |
IT1317735B1 (en) | 2000-01-26 | 2003-07-15 | Nicox Sa | SALTS OF ANTIMICROBIAL AGENTS. |
DE10028810A1 (en) | 2000-06-10 | 2001-12-20 | Henkel Kgaa | Polyurethane melt adhesive composition, useful for the adhesion of leather, plastic, wood and glass, comprises a product of a polyisocyanate with a polyester block copolymer |
US6803495B2 (en) | 2000-06-28 | 2004-10-12 | World Properties, Inc. | Polyurethane foam composition and method of manufacture thereof |
US6740333B2 (en) | 2000-07-07 | 2004-05-25 | Anestic Aps | Suppository and composition comprising at least one polyethylene glycol |
JP4378667B2 (en) * | 2000-09-11 | 2009-12-09 | 東レ・オペロンテックス株式会社 | Method for producing polyurethane fiber |
DE10050137A1 (en) | 2000-10-11 | 2002-04-18 | Bayer Ag | Stabilized mono- and polyaspartic acid esters |
DE10051392A1 (en) | 2000-10-17 | 2002-04-18 | Bayer Ag | Binder for preparation of electrically insulating lacquers comprises specific polyurethane(s), organic solvents, and optional adjuvants and additives |
JP5027962B2 (en) | 2000-10-19 | 2012-09-19 | Dic株式会社 | Method for producing liquid urethane prepolymer and resin composition |
US6811549B2 (en) | 2001-02-16 | 2004-11-02 | William H. Fleming | Administration of therapeutic or diagnostic agents using interlabial pad |
DE10112366B4 (en) | 2001-03-15 | 2006-06-08 | Bayer Materialscience Ag | Aliphatic thermoplastic polyurethanes and their use |
US6881788B2 (en) | 2001-08-21 | 2005-04-19 | Mitsui Takeda Chemicals, Inc. | Polyurethane resin water dispersion and aqueous polyurethane adhesive |
US20050090474A1 (en) | 2002-01-16 | 2005-04-28 | Zvi Naor | Methods and compositions for enhancing and inhibiting fertilization |
CH697081A5 (en) | 2002-01-22 | 2008-04-30 | Andreas F Dr Schaub | Composition for supporting the birth of a human fetuses. |
US20060052341A1 (en) | 2002-02-08 | 2006-03-09 | Brian Cornish | Control of a biological function |
NZ517094A (en) | 2002-02-08 | 2005-03-24 | Advanced Animal Technology Ltd | Improvements in and relating to substance delivery device |
US6861503B2 (en) | 2002-02-27 | 2005-03-01 | Poly-Med, Inc. | Interlinked solid polyethylene glycols and copolymers thereof |
US7358295B2 (en) | 2002-04-05 | 2008-04-15 | Lubrizol Advanced Materials, Inc. | Hybrid polymer composition, and article therefrom |
FR2840907B1 (en) * | 2002-06-14 | 2005-11-25 | Polymerexpert Sa | ENHANCED THERMO-SENSITIVE POLYMER CAPABLE OF FORMING HIGH VISCOSIFICATION INJECTABLE THERMOREVERSIBLE GELS |
US7179481B2 (en) | 2002-09-19 | 2007-02-20 | Kimberly-Clark Worldwide, Inc. | Vaginal health products |
WO2004039323A2 (en) | 2002-10-28 | 2004-05-13 | Tyco Healthcare Group Lp | Fast curing compositions |
US20040142847A1 (en) | 2002-11-21 | 2004-07-22 | Rolf Bayersdoerfer | Detergent tablets with polyurethane coating |
US6841574B2 (en) | 2003-01-03 | 2005-01-11 | Nexmed Holdings, Inc. | Topical stabilized prostaglandin E compound dosage forms |
US20050181030A1 (en) | 2003-01-03 | 2005-08-18 | Mo Y. J. | Topical stabilized prostaglandin E compound dosage forms |
WO2004065450A2 (en) | 2003-01-16 | 2004-08-05 | Carnegie Mellon University | Biodegradable polyurethanes and use thereof |
GB0301577D0 (en) | 2003-01-23 | 2003-02-26 | Edko Pazarlama Tanitim Ltd Sti | Topical pharmaceutical and/or cosmetic dispense systems |
GB0306977D0 (en) | 2003-03-26 | 2003-04-30 | Metris Therapeutics Ltd | Device |
WO2004091579A1 (en) | 2003-04-16 | 2004-10-28 | Pharmacia Corporation | Stabilized prostaglandin formulation |
US7833545B2 (en) | 2003-04-29 | 2010-11-16 | The General Hospital Corporation | Methods and devices for the sustained release of multiple drugs |
US20040266688A1 (en) | 2003-05-14 | 2004-12-30 | Nayak Nihar R | Methods for modulating endometrium |
US8399013B2 (en) | 2003-06-26 | 2013-03-19 | Poly-Med, Inc. | Partially absorbable fiber-reinforced composites for controlled drug delivery |
US8404272B2 (en) | 2003-06-26 | 2013-03-26 | Poly-Med, Inc. | Fiber-reinforced composite rings for intravaginal controlled drug delivery |
WO2005004837A1 (en) | 2003-07-10 | 2005-01-20 | Galen (Chemicals) Limited | Intravaginal drug delivery devices |
WO2005013906A2 (en) | 2003-08-08 | 2005-02-17 | Sri International | pH-RESPONSIVE FILM FOR INTRAVAGINAL DELIVERY OF A BENEFICIAL AGENT |
AU2004274000B2 (en) | 2003-09-19 | 2009-07-30 | Drugtech Corporation | Pharmaceutical delivery system |
ATE289514T1 (en) | 2003-11-03 | 2005-03-15 | Peter-Hansen Volkmann | VAGINAL CARE COMPOSITION |
EP1555278A1 (en) | 2004-01-15 | 2005-07-20 | Innocore Technologies B.V. | Biodegradable multi-block co-polymers |
MXPA06007493A (en) | 2004-01-28 | 2007-04-17 | New Condensator Inc | Apparatus for removing contaminants from crankcase emissions. |
US20050169975A1 (en) | 2004-02-03 | 2005-08-04 | Nitto Denko Corporation | Film base material for adhesive skin patch and adhesive skin patch |
DE102004008015A1 (en) | 2004-02-19 | 2005-09-08 | Cognis Deutschland Gmbh & Co. Kg | Thickener for polyurethane base |
CN1950098B (en) | 2004-03-24 | 2013-02-27 | 宝利诺沃生物材料有限公司 | Biodegradable polyurethane and polyurethane ureas |
AU2005231738A1 (en) | 2004-03-26 | 2005-10-20 | Katz, David F. Mr | Bioresponsive polymer system for delivery of microbicides |
EP1741454B1 (en) | 2004-03-29 | 2011-06-29 | Sanyo Chemical Industries, Ltd. | Medical adhesive |
US20080140185A1 (en) | 2004-04-15 | 2008-06-12 | University Of Utah Research Foundation | Biodegradable and Biocompatible Peg-Based Poly(Ester-Urethanes) |
US7485666B2 (en) | 2004-06-17 | 2009-02-03 | Kimberly-Clark Worldwide, Inc. | Vaginal health products |
US20060003950A1 (en) | 2004-06-30 | 2006-01-05 | Bone Care International, Inc. | Method of treating prostatic diseases using a combination of vitamin D analogues and other agents |
DE102004031786A1 (en) | 2004-07-01 | 2006-01-26 | Cognis Deutschland Gmbh & Co. Kg | Polyurethane-based thickener |
DK1768625T3 (en) | 2004-07-09 | 2011-05-09 | Population Council Inc | Sustained release compositions containing progesterone receptor modulators |
US8460378B2 (en) | 2004-07-26 | 2013-06-11 | DePuy Sythes Products, LLC | Biocompatible, biodegradable polyurethane materials with controlled hydrophobic to hydrophilic ratio |
GB0417401D0 (en) | 2004-08-05 | 2004-09-08 | Controlled Therapeutics Sct | Stabilised prostaglandin composition |
WO2006024138A1 (en) | 2004-08-30 | 2006-03-09 | Taro Pharmaceutical Industries Ltd. | A thermoreversible pharmaceutical formulation for anti-microbial agents comprising poloxamer polymers and hydroxy fatty acid ester of polyethylene glycol |
US20060093675A1 (en) | 2004-10-29 | 2006-05-04 | Mathew Ebmeier | Intravaginal treatment of vaginal infections with metronidazole compositions |
GB0424526D0 (en) | 2004-11-05 | 2004-12-08 | Controlled Therapeutics Sct | Hydrogel delivery vehicle |
WO2006084082A1 (en) | 2005-02-03 | 2006-08-10 | Duramed Pharmaceuticals, Inc. | Compositions of unconjugated estrogens and methods for their use |
US7795467B1 (en) * | 2005-04-26 | 2010-09-14 | Advanced Cardiovascular Systems, Inc. | Bioabsorbable, biobeneficial polyurethanes for use in medical devices |
TW200744610A (en) | 2005-06-21 | 2007-12-16 | Organon Nv | New regimens for controlled drug delivery devices for contraception |
TW200727920A (en) | 2005-06-21 | 2007-08-01 | Organon Nv | New regimens for oral monophasic contraceptives |
CA2615393C (en) | 2005-07-19 | 2011-09-20 | The Population Council, Inc. | Methods and compositions for emergency contraception using endothelin receptor antagonists |
JP2009518129A (en) | 2005-12-06 | 2009-05-07 | タイコ ヘルスケア グループ リミテッド パートナーシップ | Bioabsorbable surgical composition |
US8449714B2 (en) | 2005-12-08 | 2013-05-28 | Covidien Lp | Biocompatible surgical compositions |
US20070148105A1 (en) | 2005-12-22 | 2007-06-28 | Donald Spector | Compositions and methods comprising magnetic particles for health use |
US20090061172A1 (en) | 2006-01-26 | 2009-03-05 | Komatsu Seiren Co., Ltd. | Polyurethane Resin Composition for Durable Moisture-Permeable Waterproof Sheet, Moisture-Permeable Waterproof Sheet and Method of Manufacturing the Same |
EP1994212A1 (en) | 2006-03-06 | 2008-11-26 | Basf Se | Nonwoven based on thermoplastic polyurethane |
EP2012803A4 (en) | 2006-04-20 | 2012-08-01 | Univ Utah Res Found | Polymeric compositions and methods of making and using thereof |
GB0613333D0 (en) | 2006-07-05 | 2006-08-16 | Controlled Therapeutics Sct | Hydrophilic polyurethane compositions |
US8177706B2 (en) | 2006-07-10 | 2012-05-15 | Mcneil-Ppc, Inc. | Method of treating urinary incontinence |
US20080160065A1 (en) | 2006-07-12 | 2008-07-03 | Janet Anne Halliday | Drug delivery polymer with hydrochloride salt of clindamycin |
EP2094348A1 (en) | 2006-11-22 | 2009-09-02 | N.V. Organon | Delivery system for a non-steroidal non-ionized hydrophilic drug |
US7781651B2 (en) | 2007-04-30 | 2010-08-24 | Monsanto Technology Llc | Plants and seeds of corn variety CV715590 |
ES2696999T3 (en) | 2007-06-26 | 2019-01-21 | Allergan Pharmaceuticals Int Ltd | Devices for the intravaginal administration of drugs for the administration of macromolecules and water-soluble drugs |
EP2173362A2 (en) | 2007-06-27 | 2010-04-14 | University Of Utah | Compositions and methods for inhibiting viral and bacterial activity |
US8741329B2 (en) | 2007-09-21 | 2014-06-03 | Merck Sharp & Dohme B.V. | Drug delivery system |
US9426414B2 (en) | 2007-12-10 | 2016-08-23 | Qualcomm Incorporated | Reference selection for video interpolation or extrapolation |
WO2009094573A2 (en) | 2008-01-25 | 2009-07-30 | The University Of Utah Research Foundation | Linear order release polymer |
FI20085277A0 (en) | 2008-04-02 | 2008-04-02 | Bayer Schering Pharma Oy | Intrauterine system |
US20110150955A1 (en) | 2009-12-23 | 2011-06-23 | Shannon Elizabeth Klingman | Products and Methods for Reducing Malodor from the Pudendum |
-
2006
- 2006-07-08 GB GBGB0613638.6A patent/GB0613638D0/en not_active Ceased
-
2007
- 2007-06-27 JP JP2009517399A patent/JP5307710B2/en active Active
- 2007-06-27 AT AT07733405T patent/ATE498643T1/en active
- 2007-06-27 CN CN2007800256285A patent/CN101484495B/en active Active
- 2007-06-27 BR BRPI0713481A patent/BRPI0713481B8/en active IP Right Grant
- 2007-06-27 CA CA2656788A patent/CA2656788C/en active Active
- 2007-06-27 WO PCT/GB2007/002415 patent/WO2008007046A1/en active Application Filing
- 2007-06-27 PT PT07733405T patent/PT2038325E/en unknown
- 2007-06-27 PL PL07733405T patent/PL2038325T3/en unknown
- 2007-06-27 AU AU2007274119A patent/AU2007274119B2/en active Active
- 2007-06-27 ES ES07733405T patent/ES2363704T3/en active Active
- 2007-06-27 DE DE602007012545T patent/DE602007012545D1/en active Active
- 2007-06-27 DK DK07733405.0T patent/DK2038325T3/en active
- 2007-06-27 US US12/373,002 patent/US8361272B2/en active Active
- 2007-06-27 EP EP07733405A patent/EP2038325B1/en active Active
-
2012
- 2012-09-06 US US13/605,689 patent/US8361273B2/en active Active
-
2013
- 2013-03-05 JP JP2013043282A patent/JP5639673B2/en active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1991002763A1 (en) * | 1989-08-15 | 1991-03-07 | British Technology Group Plc | Polymeric materials |
DE19842636A1 (en) * | 1997-09-24 | 1999-03-25 | Henkel Kgaa | Polyurethane adhesive bonding paper labels to polyolefin bottles |
WO2004029125A1 (en) * | 2002-09-27 | 2004-04-08 | Controlled Therapeutics (Scotland) Limited | Water-swellable polymers |
Cited By (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2244782A2 (en) | 2008-01-25 | 2010-11-03 | The University of Utah Research Foundation | Linear order release polymer |
WO2011039418A1 (en) * | 2009-10-01 | 2011-04-07 | Bayer Schering Pharma Oy | An intrauterine system |
EA019061B1 (en) * | 2009-10-01 | 2013-12-30 | Байер Ой | An intrauterine system |
AU2010302550B2 (en) * | 2009-10-01 | 2014-02-06 | Bayer Oy | An intrauterine system |
US9949869B2 (en) | 2009-10-01 | 2018-04-24 | Bayer Oy | Intrauterine system |
US9427400B2 (en) | 2010-10-19 | 2016-08-30 | International Partnership For Microbicides | Platinum-catalyzed intravaginal rings |
US8580294B2 (en) | 2010-10-19 | 2013-11-12 | International Partnership For Microbicides | Platinum-catalyzed intravaginal rings |
EP2826463A4 (en) * | 2012-03-13 | 2015-12-02 | Sumitomo Seika Chemicals | Cosmetic composition |
US9795557B2 (en) | 2012-03-13 | 2017-10-24 | Sumitomo Seika Chemicals Co., Ltd. | Cosmetic composition |
WO2015044415A1 (en) * | 2013-09-30 | 2015-04-02 | Universiteit Gent | Polyurethanes as oral drug delivery platform |
WO2015057505A1 (en) * | 2013-10-15 | 2015-04-23 | Lubrizol Advanced Materials, Inc. | Thermoplastic polyurethanes made with tin-free catalysts |
US11259956B2 (en) | 2013-11-14 | 2022-03-01 | International Partnership For Microbicides, Inc. | Combination therapy intravaginal rings |
US11793669B2 (en) | 2013-11-14 | 2023-10-24 | The Population Council, Inc. | Combination therapy intravaginal rings |
US10137031B2 (en) | 2013-11-14 | 2018-11-27 | International Partnership For Microbicides, Inc. | Combination therapy intravaginal rings |
US20180008535A1 (en) * | 2014-11-07 | 2018-01-11 | Ferring B.V. | Drug-Device Unit Containing Quinagolide |
EA033806B1 (en) * | 2014-11-07 | 2019-11-27 | Ferring Bv | Polymeric drug-device unit comprising quinagolide, method of making same, use thereof and kit comprising same |
EA033806B9 (en) * | 2014-11-07 | 2019-12-19 | Ферринг Б.В. | Polymeric drug-device unit comprising quinagolide, method of making same, use thereof and kit comprising same |
AU2015341734B2 (en) * | 2014-11-07 | 2020-08-20 | Ferring B.V. | Drug-device unit containing quinagolide |
AU2015341734C1 (en) * | 2014-11-07 | 2020-12-17 | Ferring B.V. | Drug-device unit containing quinagolide |
EP3892261A1 (en) | 2014-11-07 | 2021-10-13 | Ferring B.V. | Drug-device unit containing quinagolide |
US20220040094A1 (en) * | 2014-11-07 | 2022-02-10 | Ferring B.V. | Drug-device unit containing quinagolide |
WO2016071466A1 (en) | 2014-11-07 | 2016-05-12 | Ferring B.V. | Drug-device unit containing quinagolide |
EP3017809A1 (en) | 2014-11-07 | 2016-05-11 | Ferring B.V. | Drug-device unit containing quinagolide |
WO2023031218A1 (en) | 2021-08-31 | 2023-03-09 | Ferring B.V. | Diagnosis and treatment of ectopic endometriosis |
Also Published As
Publication number | Publication date |
---|---|
BRPI0713481A2 (en) | 2012-11-06 |
AU2007274119B2 (en) | 2013-01-31 |
AU2007274119A1 (en) | 2008-01-17 |
DE602007012545D1 (en) | 2011-03-31 |
US20090324692A1 (en) | 2009-12-31 |
JP2013151517A (en) | 2013-08-08 |
PL2038325T3 (en) | 2011-07-29 |
BRPI0713481B8 (en) | 2021-05-25 |
JP2009542831A (en) | 2009-12-03 |
JP5307710B2 (en) | 2013-10-02 |
BRPI0713481B1 (en) | 2019-08-13 |
CA2656788A1 (en) | 2008-01-17 |
DK2038325T3 (en) | 2011-05-30 |
US20120329883A1 (en) | 2012-12-27 |
CN101484495B (en) | 2011-12-28 |
EP2038325A1 (en) | 2009-03-25 |
PT2038325E (en) | 2011-05-02 |
US8361273B2 (en) | 2013-01-29 |
ES2363704T3 (en) | 2011-08-12 |
CA2656788C (en) | 2015-01-27 |
US8361272B2 (en) | 2013-01-29 |
GB0613638D0 (en) | 2006-08-16 |
EP2038325B1 (en) | 2011-02-16 |
ATE498643T1 (en) | 2011-03-15 |
CN101484495A (en) | 2009-07-15 |
JP5639673B2 (en) | 2014-12-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CA2656788C (en) | Controlled release composition comprising polyurethane elastomers | |
EP2035476B1 (en) | Hydrophilic polyurethane compositions | |
EP2520280A2 (en) | Water-swellable polymer with misoprostol | |
US8524254B2 (en) | Bioresorbable polymers | |
AU2013205539B2 (en) | Polyurethane elastomers | |
EP3017809A1 (en) | Drug-device unit containing quinagolide |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 200780025628.5 Country of ref document: CN |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 07733405 Country of ref document: EP Kind code of ref document: A1 |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2007274119 Country of ref document: AU Ref document number: 10326/DELNP/2008 Country of ref document: IN |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2007733405 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref document number: 2656788 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2009517399 Country of ref document: JP |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
ENP | Entry into the national phase |
Ref document number: 2007274119 Country of ref document: AU Date of ref document: 20070627 Kind code of ref document: A |
|
NENP | Non-entry into the national phase |
Ref country code: RU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 12373002 Country of ref document: US |
|
ENP | Entry into the national phase |
Ref document number: PI0713481 Country of ref document: BR Kind code of ref document: A2 Effective date: 20090107 |