US20110052708A1 - Methods and formulations for the delivery of pharmacologically active agents - Google Patents
Methods and formulations for the delivery of pharmacologically active agents Download PDFInfo
- Publication number
- US20110052708A1 US20110052708A1 US12/713,092 US71309210A US2011052708A1 US 20110052708 A1 US20110052708 A1 US 20110052708A1 US 71309210 A US71309210 A US 71309210A US 2011052708 A1 US2011052708 A1 US 2011052708A1
- Authority
- US
- United States
- Prior art keywords
- paclitaxel
- formulation
- cremophor
- administration
- albumin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 120
- 238000009472 formulation Methods 0.000 title claims abstract description 118
- 238000000034 method Methods 0.000 title claims description 24
- 239000013543 active substance Substances 0.000 title description 28
- 229960001592 paclitaxel Drugs 0.000 claims description 135
- 229930012538 Paclitaxel Natural products 0.000 claims description 133
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 132
- 239000008389 polyethoxylated castor oil Substances 0.000 claims description 46
- 206010028980 Neoplasm Diseases 0.000 claims description 42
- 102000009027 Albumins Human genes 0.000 claims description 14
- 108010088751 Albumins Proteins 0.000 claims description 14
- 239000002105 nanoparticle Substances 0.000 claims description 12
- 210000001519 tissue Anatomy 0.000 claims description 12
- 230000001413 cellular effect Effects 0.000 claims description 7
- 230000003834 intracellular effect Effects 0.000 claims description 7
- 210000004072 lung Anatomy 0.000 claims description 6
- 210000004881 tumor cell Anatomy 0.000 claims description 6
- 238000001990 intravenous administration Methods 0.000 claims description 5
- 102000008100 Human Serum Albumin Human genes 0.000 claims 4
- 108091006905 Human Serum Albumin Proteins 0.000 claims 4
- 210000000988 bone and bone Anatomy 0.000 claims 4
- 210000002216 heart Anatomy 0.000 claims 4
- 210000003734 kidney Anatomy 0.000 claims 4
- 210000000496 pancreas Anatomy 0.000 claims 4
- 210000000952 spleen Anatomy 0.000 claims 4
- 210000002307 prostate Anatomy 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 abstract description 27
- 229940079593 drug Drugs 0.000 abstract description 23
- 239000003814 drug Substances 0.000 abstract description 23
- 230000000694 effects Effects 0.000 abstract description 11
- 230000002209 hydrophobic effect Effects 0.000 abstract description 8
- 239000003795 chemical substances by application Substances 0.000 description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 210000002381 plasma Anatomy 0.000 description 23
- 210000003743 erythrocyte Anatomy 0.000 description 13
- 230000004044 response Effects 0.000 description 10
- 238000010172 mouse model Methods 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 7
- 230000002035 prolonged effect Effects 0.000 description 6
- 239000003981 vehicle Substances 0.000 description 6
- 239000008280 blood Substances 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 210000000170 cell membrane Anatomy 0.000 description 4
- 239000000693 micelle Substances 0.000 description 4
- 238000000638 solvent extraction Methods 0.000 description 4
- 206010006187 Breast cancer Diseases 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 231100000517 death Toxicity 0.000 description 3
- 239000010432 diamond Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 238000005192 partition Methods 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 230000032258 transport Effects 0.000 description 3
- 206010055113 Breast cancer metastatic Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 231100001231 less toxic Toxicity 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 238000002203 pretreatment Methods 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000000560 biocompatible material Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000005068 bladder tissue Anatomy 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- -1 for example Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 231100000171 higher toxicity Toxicity 0.000 description 1
- 230000002706 hydrostatic effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 210000003093 intracellular space Anatomy 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 125000003473 lipid group Chemical group 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- 231100000682 maximum tolerated dose Toxicity 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- 239000002077 nanosphere Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 208000023958 prostate neoplasm Diseases 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
Images
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
- A61K9/0026—Blood substitute; Oxygen transporting formulations; Plasma extender
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6921—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
- A61K47/6925—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a microcapsule, nanocapsule, microbubble or nanobubble
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6921—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
- A61K47/6927—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/0002—General or multifunctional contrast agents, e.g. chelated agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
- A61K49/222—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by a special physical form, e.g. emulsions, liposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
- A61K49/222—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by a special physical form, e.g. emulsions, liposomes
- A61K49/223—Microbubbles, hollow microspheres, free gas bubbles, gas microspheres
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
- A61K49/222—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by a special physical form, e.g. emulsions, liposomes
- A61K49/226—Solutes, emulsions, suspensions, dispersions, semi-solid forms, e.g. hydrogels
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5052—Proteins, e.g. albumin
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5138—Organic macromolecular compounds; Dendrimers obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5161—Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5169—Proteins, e.g. albumin, gelatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
Abstract
Description
- The present application is a continuation of U.S. Ser. No. 11/240,940, filed Sep. 29, 2005, now pending, which is a continuation of U.S. Ser. No. 10/146,706, filed May 14, 2002, now abandoned, which is a continuation-in-part of U.S. Ser. No. 09/628,388, filed Aug. 1, 2000, now issued U.S. Pat. No. 6,506,405, which is a divisional of U.S. Ser. No. 08/926,155, filed Sep. 9, 1997, now issued as U.S. Pat. No. 6,096,331, which is a continuation-in-part of U.S. Ser. No. 08/720,756, filed Oct. 1, 1996, now issued as U.S. Pat. No. 5,916,596, and U.S. Ser. No. 08/485,448, filed Jun. 7, 1995, now U.S. Pat. No. 5,665,382, which is, in turn, a continuation-in-part of U.S. Ser. No. 08/200,235, filed Feb. 22, 1994, now issued as U.S. Pat. No. 5,498,421, which is, in turn, a continuation-in-part of U.S. Ser. No. 08/023,698, filed Feb. 22, 1993, now issued as U.S. Pat. No. 5,439,686 and U.S. Ser. No. 08/035,150, filed Mar. 26, 1993, now issued as U.S. Pat. No. 5,362,478, the content of each of which are hereby incorporated by reference therein in their entirety.
- The present invention relates to novel formulations of pharmacologically active agents and methods for the delivery of such agents to subjects in need thereof.
- In the quest for next generation therapies to treat cancer, scientist often discover promising compounds only to find that the molecule is highly insoluble in water, and hence impossible to deliver intravenously. Such was the problem with paclitaxel, an extremely effective anti-tumor agent discovered over a quarter century ago by the Nation Cancer Institute. Despite almost 30 years of effort, the only method currently approved to address this problem of water-insolubility of paclitaxel is the use of a toxic solvent (cremophor) to dissolve the drug, and administer this solvent-paclitaxel mixture over many hours using specialized intra-venous tubing sets to prevent the leaching of plasticizers. This solvent-drug mixture, currently marketed in branded and generic forms, has become the most widely used anti-cancer agent as it has shown activity in breast, lung and ovarian cancer and is undergoing multiple clinical trials exploring its application in combination with other drugs for other solid tumors.
- The cremophor formulation of paclitaxel is associated with significant side-effects including life-threatening allergic reactions requiring the need for steroid pre-treatment for every patient receiving the drug, and severe infections as a result of lowering of white blood cells requiring the need for expensive blood cell growth factors. Ultimately these toxicities result in dose-limitation of cremophor-based paclitaxel formulations, thus limiting the full potential of the very effective paclitaxel molecule.
- While the above toxic side effects of cremophor paclitaxel formulations are well known, it has not been widely recognized by scientists in the field that the presence of cremophor creates a more serious impediment to realizing the maximal potential of paclitaxel by entrapping paclitaxel within the hydrophobic cores of cremophor micelles within microdroplets in the blood-stream. The entrapment effect of cremophor is dependent on cremophor concentration. Thus, increasing the doses of cremophor solutions of paclitaxel can potentially worsen the entrapment by raising the concentration of cremophor, leading to higher toxicities but none of the potential benefits of higher doses of paclitaxel, since much of the active molecule is unavailable to the intra-cellular space, where it is needed to act.
- This entrapment of paclitaxel by cremophor has a profound effect on the intra-cellular availability of the active molecule and hence may have significant clinical implications in terms of clinical outcome. Accordingly, there is a need in the art for new formulations for the delivery of substantially water insoluble pharmacologically active agents, such as paclitaxel, which do not suffer from the drawbacks of cremophor.
- In accordance with the present invention, novel formulations have been developed which are much more effective for the delivery of hydrophobic drugs to patients in need thereof than are prior art formulations. Invention formulations are capable of delivering more drug in shorter periods of time, with reduced side effects caused by the pharmaceutical carrier employed for delivery.
-
FIG. 1 collectively compares the plasma kinetics of radiolabelled paclitaxel when administered to a mouse model as part of a Taxol formulation (closed squares) or as part of in invention formulation (diamonds; ABI-007).FIG. 1A indicates plasma radioactivity measured up to 0.5 hours after administration.FIG. 1B indicates plasma radioactivity measured up to 24 hours after administration. Inspection of the figure reveals that 2-5 fold higher levels of paclitaxel are retained in the plasma up to 3 hours after administration when paclitaxel is administered in a cremophor-based formulation (Taxol). Due to the reduced rate of metabolism for ABI-007, plasma levels of paclitaxel are higher after 8 hours when administered in an invention formulation, relative to a cremophor-based formulation. -
FIG. 2 compares the partitioning of paclitaxel between red blood cells and plasma when administered to a mouse model as part of a Taxol formulation (closed squares) or as part of in invention formulation (diamonds; ABI-007). Inspection of the figure reveals that the blood/plasma ratio for paclitaxel administered as part of a cremophor-based formulation (Taxol) in the first 3 hours after administration is about 1.5-2, indicating that the majority of paclitaxel is retained in the plasma due to micellar formation with cremophor. In addition, it is seen that paclitaxel in a cremophor-based formulation does not significantly partition into the red blood cells. In contrast, paclitaxel administered as part of an invention formulation readily partitions into the red blood cells. -
FIG. 3 summarizes tumor/plasma partitioning kinetics of paclitaxel when administered to a mouse model as part of a Taxol formulation (closed squares) or as part of in invention formulation (diamonds; ABI-007). It is seen that the tumor/plasma ratio of paclitaxel increases significantly over the first 3 hours when as part of an invention formulation, as opposed to a Taxol formulation. -
FIG. 4 compares the response of mammary carcinoma in a mouse model to exposure to ABI-007 or Taxol. -
FIG. 5 compares the response of ovarian carcinoma in a mouse model to exposure to ABI-007 or Taxol. -
FIG. 6 compares the response of prostate tumors in a mouse model to exposure to ABI-007 or Taxol. -
FIG. 7 compares the response of colon tumors in a mouse model to exposure to ABI-007 or Taxol. -
FIG. 8 compares the response of lung tumors in a mouse model to exposure to ABI-007 or Taxol. - In accordance with the present invention, there are provided methods for the delivery of a substantially water insoluble pharmacologically active agent to a subject in need thereof, said method comprising combining said agent with an effective amount of a pharmaceutically acceptable carrier which is substantially free of micelle-forming components, and administering an effective amount of said combination to said subject.
- As readily recognized by those of skill in the art, a wide variety of pharmacologically active agents are contemplated for use in the practice of the present invention. A presently preferred agent contemplated for use herein is paclitaxel.
- Pharmaceutically acceptable carriers contemplated for use in the practice of the present invention are biocompatible materials such as albumin.
- Micelle-forming components which are preferably avoided in the practice of the present invention are surface active materials which are commonly used to assist in solubilizing substantially insoluble compounds in aqueous media, such as, for example, cremophor.
- Invention combination of active agent and pharmaceutically acceptable carrier can be administered in a variety of ways, such as, for example, by oral, intravenous, subcutaneous, intraperitoneal, intrathecal, intramuscular, intracranial, inhalational, topical, transdermal, rectal, or pessary routes of administration, and the like.
- In accordance with another embodiment of the present invention, there are provided methods to reduce entrapment of a substantially water insoluble pharmacologically active agent in vehicle employed for delivery thereof, said method comprising combining said agent with a pharmaceutically acceptable carrier which is substantially free of micelle-forming components prior to delivery thereof.
- Presently preferred pharmaceutically acceptable carriers contemplated for use herein are those having substantially lower affinity for said agent than does the micelle-forming component. Thus, for example, while cremophor has the benefit of aiding in the solubilization of agent, it has the disadvantage of having a substantial affinity for the agent, so that release of the agent from the carrier becomes a limitation on the bioavailability of the agent. In contrast, carriers contemplated herein, such as, for example, albumin, readily release the active agent to the active site and are thus much more effective for treatment of a variety of conditions.
- In accordance with yet another embodiment of the present invention, there are provided methods to reduce entrapment of a substantially water insoluble pharmacologically active agent in vehicle employed for delivery thereof, said method comprising employing pharmaceutically acceptable carriers which are substantially free of micelle-forming components in aqueous media as the vehicle for delivery of said agent.
- In accordance with still another embodiment of the present invention, there are provided methods to prolong exposure of a subject to a substantially water insoluble pharmacologically active agent upon administration thereof to a subject in need thereof, said method comprising combining said agent with pharmaceutically acceptable carrier(s) which is (are) substantially free of micelle-forming components prior to delivery thereof.
- In accordance with a further embodiment of the present invention, there are provided methods to facilitate transport of a substantially water insoluble pharmacologically active agent across cell membranes upon administration thereof to a subject in need thereof, said method comprising combining said agent with pharmaceutically acceptable carrier(s) which is (are) substantially free of micelle-forming components prior to delivery thereof.
- In accordance with a still further embodiment of the present invention, there are provided methods to facilitate transport of a substantially water insoluble pharmacologically active agent into the cellular compartment upon administration thereof to a subject in need thereof, said method comprising combining said agent with pharmaceutically acceptable carrier(s) which is (are) substantially free of micelle-forming components prior to delivery thereof.
- In accordance with another embodiment of the present invention, there are provided formulations comprising a substantially water insoluble pharmacologically active agent and a pharmaceutically acceptable carrier which is substantially free of micelle-forming components, wherein said formulation provides a higher concentration of said agent in the cellular compartment than a formulation of the same agent with a micelle-forming component.
- In accordance with yet another embodiment of the present invention, there are provided formulations comprising a substantially water insoluble pharmacologically active agent and a pharmaceutically acceptable carrier which is substantially free of micelle-forming components, wherein said formulation provides increased intra-cellular availability of said agent relative to a formulation of the same agent with a micelle-forming component.
- In accordance with still another embodiment of the present invention, there are provided formulations comprising a substantially water insoluble pharmacologically active agent and a pharmaceutically acceptable carrier which is substantially free of micelle-forming components, wherein said formulation provides prolonged activity of said agent relative to a formulation of the same agent with a micelle-forming component.
- In accordance with a further embodiment of the present invention, there are provided formulations comprising a substantially water insoluble pharmacologically active agent and a pharmaceutically acceptable carrier which is substantially free of micelle-forming components, wherein said formulation facilitates delivery of said agent to red blood cells.
- In accordance with another embodiment of the present invention, there are provided formulations comprising a substantially water insoluble pharmacologically active agent and a pharmaceutically acceptable carrier which is substantially free of micelle-forming components, wherein said formulation releases a portion of said agent contained therein to the lipid membrane of a cell.
- In accordance with yet another embodiment of the present invention, there are provided formulations comprising a substantially water insoluble pharmacologically active agent and a pharmaceutically acceptable carrier which is substantially free of micelle-forming components, wherein said formulation provides reduced levels of said agent in the bloodstream relative to a formulation of the same agent with a micelle-forming component.
- In accordance with still another embodiment of the present invention, there are provided formulations comprising a substantially water insoluble pharmacologically active agent and a pharmaceutically acceptable carrier which is substantially free of micelle-forming components, wherein said formulation delivers said agent to the bloodstream over an extended period of time relative to a formulation of the same agent with a micelle-forming component.
- In accordance with a further embodiment of the present invention, there are provided formulations comprising a substantially water insoluble pharmacologically active agent and a pharmaceutically acceptable carrier which is substantially free of micelle-forming components, wherein the rate of metabolism of said agent in said formulation is reduced relative to the rate of metabolism of said agent in a formulation with a micelle-forming component.
- In accordance with another embodiment of the present invention, there are provided formulations comprising a substantially water insoluble pharmacologically active agent and a pharmaceutically acceptable carrier which is substantially free of micelle-forming components, wherein said agent has a longer half life in said formulation relative to the half life of said agent in a formulation with a micelle-forming component.
- In accordance with yet another embodiment of the present invention, there are provided formulations comprising a substantially water insoluble pharmacologically active agent and a pharmaceutically acceptable carrier which is substantially free of micelle-forming components, wherein said formulation provides a higher red blood cell/plasma ratio of said agent than does a formulation of the same agent with a micelle-forming component.
- In accordance with still another embodiment of the present invention, there are provided formulations comprising a substantially water insoluble pharmacologically active agent and a pharmaceutically acceptable carrier which is substantially free of micelle-forming components, wherein said formulation provides a higher tumor/plasma ratio of said agent than does a formulation of the same agent with a micelle-forming component.
- In accordance with a further embodiment of the present invention, there are provided formulations comprising a substantially water insoluble pharmacologically active agent and a pharmaceutically acceptable carrier which is substantially free of micelle-forming components, wherein the area under the curve for delivery of said agent to a tumor via said formulation is higher than the area under the curve for delivery of said agent to a tumor via a formulation of the same agent with a micelle-forming component.
- In accordance with a still further embodiment of the present invention, there are provided formulations comprising a substantially water insoluble pharmacologically active agent and a pharmaceutically acceptable carrier which is substantially free of micelle-forming components, wherein said formulation provides a higher concentration maximum (Cmax) for said agent in tumor cells than does a formulation of the same agent with a micelle-forming component.
- In accordance with another embodiment of the present invention, there are provided formulations comprising a substantially water insoluble pharmacologically active agent and a pharmaceutically acceptable carrier which is substantially free of micelle-forming components, wherein said formulation provides a lower concentration maximum (Cmax) for said agent in plasma than does a formulation of the same agent with a micelle-forming component.
- In accordance with still another embodiment of the present invention, there are provided formulations comprising a substantially water insoluble pharmacologically active agent and a pharmaceutically acceptable carrier which is substantially free of micelle-forming components, wherein said formulation provides more rapid uptake of said agent by tumor cells than does a formulation of the same agent with a micelle-forming component.
- In accordance with yet another embodiment of the present invention, there are provided formulations comprising a substantially water insoluble pharmacologically active agent and a pharmaceutically acceptable carrier which is substantially free of micelle-forming components, wherein said formulation enhances delivery of said agent to tissue, relative to a formulation of the same agent with a micelle-forming component.
- Tissues contemplated for treatment according to the invention include tumors, peritoneal tissue, bladder tissue, lung tissue, and the like.
- ABI-007 is a proprietary, cremophor-free, albumin-based paclitaxel nanoparticle, 1/100th the size of a single red blood cell. Based on several Phase I studies, it has been shown that ABI-007 can be administered rapidly without the need for steroid pre-treatment and without the need for G-CSF at a maximum tolerated dose of 300 mg/m2 given every 3 weeks. This is a significantly higher dose than is approved for cremophor-based paclitaxel formulations (Taxol) of 175 mg/m2.
- In accordance with the present invention, it has been discovered that ABI-007 acts as a novel biologic nano-transporter for hydrophobic drugs such as paclitaxel, with the capabilities of rapidly releasing paclitaxel to the cellular compartment and increasing intra-cellular availability of the active drug, where it is needed in order to have its chemo-therapeutic effect. Furthermore, through the use of the red blood cell as a secondary storage vehicle it has been discovered that in addition to the rapid and increased availability of paclitaxel at the intra-cellullar level, by the recruitment of circulating red blood cells, ABI-007 further provides a significant prolonged activity of the parent molecule with sustained in-vivo release. These novel mechanisms for rapid and increased intra-cellular availabilty of the drug at the tumor site, together with sustained trafficking of the non-metabolized paclitaxel, has potentially significant implications for the clinical outcome in the treatment of solid tumors. Indeed, the pre-clinical and Phase II clinical data presented below supports this notion.
- By taking advantage of the differences in binding affinities of albumin and the lipid bi-layer of cell membranes for hydrophobic paclitaxel, the drug-bearing albumin nanoparticle (ABI-007) would rapidly release a portion of its hydrophobic paclitaxel cargo to the lipid membrane of a cell.
- In the vascular compartment, the first cell encountered is the red blood cell. In accordance with the present invention, the red blood cell has been found to rapidly compartmentalize the paclitaxel molecule. Since the red blood cell has no nucleus and hence no microtubulin to which the paclitaxel molecule can bind, nor any degradation machinery within its core, this cell serves as an ideal secondary storage vehicle for the active paclitaxel, accounting in part for the prolonged activity of paclitaxel noted with ABI-007.
- Following partitioning of a portion of its paclitaxel payload to the circulating red blood cells, the nanoparticle is carried by the blood-stream to the hypervasular tumor, where paclitaxel is rapidly transferred to the tumor cell-membrane, again due to the differences in binding affinity. It has been well established by other groups that the hydrostatic pressure within these tumor cells is abnormally higher than the surrounding interstitium and vascular space. This abnormally high pressure, together with the fact that the vessels associated with tumors are also abnormally leaky, creates a barrier to the delivery of chemotherapeutic agents to the tumor cell. Thus, under these circumstances it is imperative that the hydrophobic paclitaxel be released rapidly to the lipid cell membrane and be bound by the microtubules within the nuclues before the drug is ejected from the tumor. Evidence presented herein indicates that ABI-007 provides that opportunity by the ability to rapidly release the hydrophobic molecule. In contrast, cremophor-based formulations entrap the paclitaxel, limiting the ability of the drug to partition into cells. This difference may have important clinical implications and may account in part for the positive data noted in the Phase II studies of ABI-007 in metastatic breast cancer and the evidence for responses in patients who had previously failed Taxol therapy
- As the nanoparticle depeletes itself of paclitaxel into the cellular compartment within the first 3-8 hours following infusion, the plasma concentration of paclitaxel diminshes. At this juncture, paclitaxel (still in its active, non-metabolized form) follows the concentration gradient and is now transferred to albumin again, and is again carried to the tumor bed. Thus, a prolonged half-life of paclitaxel has been achieved, with sustained release and ultimately higher tumor concentration of the drug.
- The invention will now be described in greater detail by reference to the following non-limiting examples.
- Using radio labeled paclitaxel, the enahanced intra-cellular availability of paclitaxel has been confirmed following injection of ABI-007. In addition, the entrapment of Cremophor-bound paclitaxel has also been confirmed. This difference in findings correlates with in-vivo studies in mice bearing human breast cancer, with the finding that ABI-007 at equi-dose to Taxol, resulted in improved outcomes that these 130 nanometer size particles distributed throughout the body.
- Thus, human MX-1 mammary tumor fragments were implanted subcutaneously in female athymic mice. Radiolabelled drug was administered when tumors reached about 500 mm3. Tritium-labelled ABI-007 or tritium-labelled Taxol were administered at a dose of 20 mg/kg. Both groups received about 7-10 μCi/mouse of tritium-labelled paclitaxel. Saline was used as the diluent for both drugs. At various time points (5 min, 15 min, 30 min, 1 hr, 3 hr, 8 hr and 24 hr), 4 animals were sacrificed, then blood samples and tumor were recovered for radioactivity assessment.
- Radioactivity was determined as nCi/ml of whole blood and plasma, and nCi/g of tumor tissue. Results are presented in
FIGS. 1 , 2 and 3, and are standardized for radioactivity and paclitaxel dose. The data from these studies are also presented in the following tables. -
-
New AUC0-inf AUC0-24 (nCi hr/mL or g) (nCi hr/mL or g) Cmax (nCi/mL or g) Blood Plasma Tumor Blood Plasma Tumor Blood Plasma Tumor ABI-007 939 1161 5869 ABI-007 656 836 2156 ABI-007 328 473 144 Taxol 871 1438 3716 Taxol 849 1415 1804 Taxol 752 1427 117 Ratio 1.08 0.81 1.58 Ratio 0.77 0.59 1.20 Ratio 0.44 0.33 1.23 TAXOL: high Plasma AUC - paclitaxel is trapped in cremophor micelles ABI-007: higher Tumor AUC (exposure), pac distributed into cells/tissues ABI-007: Substantially lower Cmax in Plasma, blood Implies rapid distribution into cells and tissues ABI-007: higher Tumor Cmax - more effective tumor kill -
tmax (hours) t½e (hours) Vdss (mL/kg) Blood Plasma Tumor Blood Plasma Tumor Blood Plasma Tumor ABI-007 0 0 0.5 ABI-007 17.1 16.1 40.2 ABI-007 6939 5180 NA Taxol 0 0 3 Taxol 4.0 3.3 24.1 Taxol 1409 692 NA Ratio 4.28 4.88 1.67 Ratio 4.92 7.49 ABI-007: Substantially lower tumor tmax indicates rapid uptake of paclitaxel into tumor relative to taxol ABI-007: Prolonged half life relative to Taxol in blood, plasma and tumor may result in higher antitumor activity ABI-007: Substantially higher volume of distribution indicating extrensive distribution into tissues relative to Taxol - Further studies demonstrate that after 24 hours, the active ingredient of the parent molecule, paclitaxel, remains present in the bloodstream, at double the concentration of Taxol. In studies comparing radiolabelled paclitaxel in Taxol vs ABI-007, direct measurements reveal increased and prolonged levels of paclitaxel in the tumors of animals receiving ABI-007.
- Toxicity was assessed for Taxol, cremophor and ABI-007. ABI-007 was found to be 50-fold less toxic than Taxol, and 30-fold less toxic than the cremophor vehicle alone, as illustrated in the following table:
-
Agent LD50, mg/kg Taxol 9.4 Cremophor 13.7 ABI-007 448.5 - Human tumor fragments were implanted subcutaneously in female athymic mice. Treatment was initiated when tumors reached about 150 mm3. The mice received either CONTROL (saline), ABI-007 (4 dose levels: 13.4, 20, 30 and 45 mg/kg) or TAXOL (3 dose levels: 13.4, 20, and 30 mg/kg) administered I.V. daily for 5 days. Saline was used as the diluent for both drugs.
- Determination of Equitoxic dose or MTD: The Equitoxic dose or MTD for each drug was determined by satisfying one of the following criteria:
-
- a) Dose for each drug that resulted in similar body weight loss (≦20%) if no deaths were seen;
- b) If body weight loss could not be matched, the highest dose at which no deaths were seen;
- If neither a) nor b) could be satisfied, the lowest dose that resulted in similar death rate.
- Tumor response to the drugs was compared at the Equitoxic dose or MTD established as above. Results for several different tumor types are presented in
FIGS. 4-8 . - i. Entrappment of Paclitaxel By Cremophor
- Working independently at Rotterdam Cancer Institute, Dr Alex Sparreboom has reported in a series of pharmacokinetic studies involving patients receiving Taxol that cremophor “causes a profound alteration of paclitaxel accumulation in erythrocytes in a concentration-dependant manner by reducing the free drug fraction available for cellular partitioning.” He has further found that the drug trapping occurs in micelles and that these micelles act as the principal carrier of paclitaxel in the systemic circulation. Since that publication these findings have been independently confirmed by two other groups.
- ii. Improved Clinical Activity With ABI-007
- Data from Phase II shows both increased effiacacy in metastatic breast cancer patients. When compared to the published literature of response rates to Taxol, the study results showed a dramatic difference in both response rates and time of response as well as evidence of reduced toxicities associated with ABI-007. Further details can be obtained by reviewing the posters presented at ASCO.
- Although the present invention has been described in conjunction with the embodiments above, it is to be noted that various changes and modifications are apparent to those who are skilled in the art. Such changes and modifications are to be understood as included within the scope of the present invention defined by the appended claims.
Claims (17)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12/713,092 US20110052708A1 (en) | 1993-02-22 | 2010-02-25 | Methods and formulations for the delivery of pharmacologically active agents |
Applications Claiming Priority (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/023,698 US5439686A (en) | 1993-02-22 | 1993-02-22 | Methods for in vivo delivery of substantially water insoluble pharmacologically active agents and compositions useful therefor |
US08/412,726 US5560933A (en) | 1993-02-22 | 1995-03-29 | Methods for in vivo delivery of substantially water insoluble pharmacologically active agents and compositions useful therefor |
US08/720,756 US5916596A (en) | 1993-02-22 | 1996-10-01 | Protein stabilized pharmacologically active agents, methods for the preparation thereof and methods for the use thereof |
US08/926,155 US6096331A (en) | 1993-02-22 | 1997-09-09 | Methods and compositions useful for administration of chemotherapeutic agents |
US09/628,388 US6506405B1 (en) | 1993-02-22 | 2000-08-01 | Methods and formulations of cremophor-free taxanes |
US10/146,706 US20030068362A1 (en) | 1993-02-22 | 2002-05-14 | Methods and formulations for the delivery of pharmacologically active agents |
US11/240,940 US20060073175A1 (en) | 1993-02-22 | 2005-09-29 | Methods and formulations for delivery of pharmacologically active agents |
US12/051,782 US20090048331A1 (en) | 1993-02-22 | 2008-03-19 | Methods and formulations for the delivery of pharmacologically active agents |
US12/713,092 US20110052708A1 (en) | 1993-02-22 | 2010-02-25 | Methods and formulations for the delivery of pharmacologically active agents |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/051,782 Continuation US20090048331A1 (en) | 1993-02-22 | 2008-03-19 | Methods and formulations for the delivery of pharmacologically active agents |
Publications (1)
Publication Number | Publication Date |
---|---|
US20110052708A1 true US20110052708A1 (en) | 2011-03-03 |
Family
ID=21816707
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US08/023,698 Expired - Lifetime US5439686A (en) | 1993-02-22 | 1993-02-22 | Methods for in vivo delivery of substantially water insoluble pharmacologically active agents and compositions useful therefor |
US08/412,726 Expired - Lifetime US5560933A (en) | 1993-02-22 | 1995-03-29 | Methods for in vivo delivery of substantially water insoluble pharmacologically active agents and compositions useful therefor |
US12/713,092 Abandoned US20110052708A1 (en) | 1993-02-22 | 2010-02-25 | Methods and formulations for the delivery of pharmacologically active agents |
Family Applications Before (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US08/023,698 Expired - Lifetime US5439686A (en) | 1993-02-22 | 1993-02-22 | Methods for in vivo delivery of substantially water insoluble pharmacologically active agents and compositions useful therefor |
US08/412,726 Expired - Lifetime US5560933A (en) | 1993-02-22 | 1995-03-29 | Methods for in vivo delivery of substantially water insoluble pharmacologically active agents and compositions useful therefor |
Country Status (2)
Country | Link |
---|---|
US (3) | US5439686A (en) |
CN (1) | CN1839806B (en) |
Cited By (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20030199425A1 (en) * | 1997-06-27 | 2003-10-23 | Desai Neil P. | Compositions and methods for treatment of hyperplasia |
US20070087022A1 (en) * | 1996-10-01 | 2007-04-19 | Abraxis Bioscience, Inc. | Novel formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof |
US20070093547A1 (en) * | 1997-06-27 | 2007-04-26 | Desai Neil P | Novel formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof |
US20090263483A1 (en) * | 2008-04-10 | 2009-10-22 | Desai Neil P | Nanoparticle formulations and uses thereof |
US20090304805A1 (en) * | 2005-02-18 | 2009-12-10 | Desai Neil P | Combinations and modes of administration of therapeutic agents and combination therapy |
US20100048499A1 (en) * | 2006-12-14 | 2010-02-25 | Desai Neil P | Breast cancer therapy based on hormone receptor status with nanoparticles comprising taxane |
US20100166869A1 (en) * | 2007-05-03 | 2010-07-01 | Desai Neil P | Methods and compositions for treating pulmonary hypertension |
US20100183728A1 (en) * | 2007-03-07 | 2010-07-22 | Desai Neil P | Nanoparticle comprising rapamycin and albumin as anticancer agent |
US20100215751A1 (en) * | 2007-06-01 | 2010-08-26 | Desai Neil P | Methods and compositions for treating recurrent cancer |
US20110052706A1 (en) * | 2009-08-28 | 2011-03-03 | Nordmark Arzeimittel GmbH & Co. KG | Pancreatine pellets and method of producing same |
US20110118342A1 (en) * | 2005-08-31 | 2011-05-19 | Tapas De | Compositions and methods for preparation of poorly water soluble drugs with increased stability |
US8034375B2 (en) | 2005-02-18 | 2011-10-11 | Abraxis Bioscience, Llc | Combinations and modes of administration of therapeutic agents and combination therapy |
US8138229B2 (en) | 2002-12-09 | 2012-03-20 | Abraxis Bioscience, Llc | Compositions and methods of delivery of pharmacological agents |
US9149455B2 (en) | 2012-11-09 | 2015-10-06 | Abraxis Bioscience, Llc | Methods of treating melanoma |
US9370494B2 (en) | 2010-03-26 | 2016-06-21 | Abraxis Bioscience, Llc | Methods for treating hepatocellular carcinoma |
US9393318B2 (en) | 2010-03-29 | 2016-07-19 | Abraxis Bioscience, Llc | Methods of treating cancer |
US9399072B2 (en) | 2010-06-04 | 2016-07-26 | Abraxis Bioscience, Llc | Methods of treatment of pancreatic cancer |
US9446003B2 (en) | 2009-04-15 | 2016-09-20 | Abraxis Bioscience, Llc | Prion free nanoparticle compositions and methods of making thereof |
US9585960B2 (en) | 2011-12-14 | 2017-03-07 | Abraxis Bioscience, Llc | Use of polymeric excipients for lyophilization or freezing of particles |
US9962373B2 (en) | 2013-03-14 | 2018-05-08 | Abraxis Bioscience, Llc | Methods of treating bladder cancer |
US10527604B1 (en) | 2015-03-05 | 2020-01-07 | Abraxis Bioscience, Llc | Methods of assessing suitability of use of pharmaceutical compositions of albumin and paclitaxel |
US10660965B2 (en) | 2010-03-29 | 2020-05-26 | Abraxis Bioscience, Llc | Methods of enhancing drug delivery and effectiveness of therapeutic agents |
US10705070B1 (en) | 2015-03-05 | 2020-07-07 | Abraxis Bioscience, Llc | Methods of assessing suitability of use of pharmaceutical compositions of albumin and poorly water soluble drug |
US10744110B2 (en) | 2013-03-12 | 2020-08-18 | Abraxis Bioscience, Llc | Methods of treating lung cancer |
US10973806B2 (en) | 2015-06-29 | 2021-04-13 | Abraxis Bioscience, Llc | Methods of treating epithelioid cell tumors comprising administering a composition comprising nanoparticles comprising an mTOR inhibitor and an albumin |
US11497737B2 (en) | 2019-10-28 | 2022-11-15 | Abraxis Bioscience, Llc | Pharmaceutical compositions of albumin and rapamycin |
US11944708B2 (en) | 2018-03-20 | 2024-04-02 | Abraxis Bioscience, Llc | Methods of treating central nervous system disorders via administration of nanoparticles of an mTOR inhibitor and an albumin |
Families Citing this family (259)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5843089A (en) | 1990-12-28 | 1998-12-01 | Boston Scientific Corporation | Stent lining |
US5693338A (en) | 1994-09-29 | 1997-12-02 | Emisphere Technologies, Inc. | Diketopiperazine-based delivery systems |
US6221367B1 (en) | 1992-06-15 | 2001-04-24 | Emisphere Technologies, Inc. | Active agent transport systems |
US6099856A (en) | 1992-06-15 | 2000-08-08 | Emisphere Technologies, Inc. | Active agent transport systems |
US5578323A (en) | 1992-06-15 | 1996-11-26 | Emisphere Technologies, Inc. | Proteinoid carriers and methods for preparation and use thereof |
US5714167A (en) | 1992-06-15 | 1998-02-03 | Emisphere Technologies, Inc. | Active agent transport systems |
JP3746293B2 (en) * | 1993-02-22 | 2006-02-15 | アメリカン バイオサイエンス、インコーポレイテッド | Methods for in vivo delivery of biologics and compositions therefor |
US6537579B1 (en) | 1993-02-22 | 2003-03-25 | American Bioscience, Inc. | Compositions and methods for administration of pharmacologically active compounds |
US6753006B1 (en) | 1993-02-22 | 2004-06-22 | American Bioscience, Inc. | Paclitaxel-containing formulations |
US20030133955A1 (en) * | 1993-02-22 | 2003-07-17 | American Bioscience, Inc. | Methods and compositions useful for administration of chemotherapeutic agents |
US6749868B1 (en) | 1993-02-22 | 2004-06-15 | American Bioscience, Inc. | Protein stabilized pharmacologically active agents, methods for the preparation thereof and methods for the use thereof |
US20070122465A1 (en) * | 1993-02-22 | 2007-05-31 | Desai Neil P | Novel formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof |
US5439686A (en) * | 1993-02-22 | 1995-08-08 | Vivorx Pharmaceuticals, Inc. | Methods for in vivo delivery of substantially water insoluble pharmacologically active agents and compositions useful therefor |
US20030073642A1 (en) * | 1993-02-22 | 2003-04-17 | American Bioscience, Inc. | Methods and formulations for delivery of pharmacologically active agents |
US5997904A (en) * | 1993-02-22 | 1999-12-07 | American Bioscience, Inc. | Total nutrient admixtures as stable multicomponent liquids or dry powders and methods for the preparation thereof |
US5665383A (en) * | 1993-02-22 | 1997-09-09 | Vivorx Pharmaceuticals, Inc. | Methods for the preparation of immunostimulating agents for in vivo delivery |
US5916596A (en) * | 1993-02-22 | 1999-06-29 | Vivorx Pharmaceuticals, Inc. | Protein stabilized pharmacologically active agents, methods for the preparation thereof and methods for the use thereof |
US20030068362A1 (en) * | 1993-02-22 | 2003-04-10 | American Bioscience, Inc. | Methods and formulations for the delivery of pharmacologically active agents |
US6528067B1 (en) | 1993-02-22 | 2003-03-04 | American Bioscience, Inc. | Total nutrient admixtures as stable multicomponent liquids or dry powders and methods for the preparation thereof |
US5650156A (en) * | 1993-02-22 | 1997-07-22 | Vivorx Pharmaceuticals, Inc. | Methods for in vivo delivery of nutriceuticals and compositions useful therefor |
US6096331A (en) | 1993-02-22 | 2000-08-01 | Vivorx Pharmaceuticals, Inc. | Methods and compositions useful for administration of chemotherapeutic agents |
IL109403A0 (en) | 1993-04-22 | 1994-07-31 | Emisphere Tech Inc | Oral drug delivery compositions and methods |
HU213200B (en) * | 1993-05-12 | 1997-03-28 | Chinoin Gyogyszer Es Vegyeszet | The cyclodextrin or cyclodextrin derivative cluster complexes of taxol, taxotere, or taxus, pharmaceutical preparations containing them and process for their production |
US5701899A (en) * | 1993-05-12 | 1997-12-30 | The Board Of Regents Of The University Of Nebraska | Perfluorobutane ultrasound contrast agent and methods for its manufacture and use |
US5855865A (en) * | 1993-07-02 | 1999-01-05 | Molecular Biosystems, Inc. | Method for making encapsulated gas microspheres from heat denatured protein in the absence of oxygen gas |
EP2226085B1 (en) * | 1993-07-19 | 2013-11-27 | Angiotech Pharmaceuticals, Inc. | Anti-angiogenic compositions and methods of use |
US5994341A (en) * | 1993-07-19 | 1999-11-30 | Angiogenesis Technologies, Inc. | Anti-angiogenic Compositions and methods for the treatment of arthritis |
US20030203976A1 (en) | 1993-07-19 | 2003-10-30 | William L. Hunter | Anti-angiogenic compositions and methods of use |
US5965566A (en) * | 1993-10-20 | 1999-10-12 | Enzon, Inc. | High molecular weight polymer-based prodrugs |
US5965109A (en) * | 1994-08-02 | 1999-10-12 | Molecular Biosystems, Inc. | Process for making insoluble gas-filled microspheres containing a liquid hydrophobic barrier |
US5626862A (en) | 1994-08-02 | 1997-05-06 | Massachusetts Institute Of Technology | Controlled local delivery of chemotherapeutic agents for treating solid tumors |
US6001347A (en) | 1995-03-31 | 1999-12-14 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US5989539A (en) | 1995-03-31 | 1999-11-23 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
CN1151836C (en) | 1995-03-31 | 2004-06-02 | 艾米斯菲尔技术有限公司 | Compound and compositions for delivering active agents |
US6090958A (en) | 1995-03-31 | 2000-07-18 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US5606973A (en) * | 1995-06-07 | 1997-03-04 | Molecular Biosystems, Inc. | Liquid core microdroplets for ultrasound imaging |
US5824345A (en) | 1995-06-07 | 1998-10-20 | Emisphere Technologies, Inc. | Fragrances and flavorants |
US6565842B1 (en) | 1995-06-07 | 2003-05-20 | American Bioscience, Inc. | Crosslinkable polypeptide compositions |
US5750147A (en) | 1995-06-07 | 1998-05-12 | Emisphere Technologies, Inc. | Method of solubilizing and encapsulating itraconazole |
NZ311474A (en) * | 1995-06-09 | 1997-09-22 | Euro Celtique Sa | Formulations for providing prolonged local anesthesia |
DE19681560T1 (en) | 1995-09-11 | 1998-08-20 | Emisphere Tech Inc | Process for the preparation of omega-aminoalkanoic acid derivatives from cycloalkanones |
US6395770B1 (en) * | 1995-10-26 | 2002-05-28 | Baker Norton Pharmaceuticals, Inc. | Method and compositions for administering taxanes orally to human patients |
US6245747B1 (en) | 1996-03-12 | 2001-06-12 | The Board Of Regents Of The University Of Nebraska | Targeted site specific antisense oligodeoxynucleotide delivery method |
WO1997035958A1 (en) * | 1996-03-26 | 1997-10-02 | Vivorx Pharmaceuticals, Inc. | Storage articles for prolonged viability and function of living cells |
WO1997045105A1 (en) | 1996-05-24 | 1997-12-04 | Angiotech Pharmaceuticals, Inc. | Compositions and methods for treating or preventing diseases of body passageways |
JP2000512671A (en) | 1996-06-14 | 2000-09-26 | エミスフェアー テクノロジーズ インク | Microencapsulated fragrance and preparation method |
US5849727A (en) * | 1996-06-28 | 1998-12-15 | Board Of Regents Of The University Of Nebraska | Compositions and methods for altering the biodistribution of biological agents |
US6515016B2 (en) | 1996-12-02 | 2003-02-04 | Angiotech Pharmaceuticals, Inc. | Composition and methods of paclitaxel for treating psoriasis |
AU741439B2 (en) | 1996-12-30 | 2001-11-29 | Battelle Memorial Institute | Formulation and method for treating neoplasms by inhalation |
US5804688A (en) | 1997-02-07 | 1998-09-08 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US5990166A (en) | 1997-02-07 | 1999-11-23 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US5773647A (en) * | 1997-02-07 | 1998-06-30 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US6313088B1 (en) | 1997-02-07 | 2001-11-06 | Emisphere Technologies, Inc. | 8-[(2-hydroxy-4-methoxy benzoyl) amino]-octanoic acid compositions for delivering active agents |
US6060513A (en) | 1997-02-07 | 2000-05-09 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US6358504B1 (en) | 1997-02-07 | 2002-03-19 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
JP2001521503A (en) | 1997-03-31 | 2001-11-06 | ネオルックス コーポレイション | Therapeutic inhibitors of vascular smooth muscle cells |
US5863944A (en) | 1997-04-30 | 1999-01-26 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US5962710A (en) | 1997-05-09 | 1999-10-05 | Emisphere Technologies, Inc. | Method of preparing salicyloylamino acids |
CN100462066C (en) | 1997-06-27 | 2009-02-18 | 美国生物科学有限公司 | Novel formulations of pharmacological agents, method for preparation thereof and method for use thereof |
CA2297489A1 (en) | 1997-07-30 | 1999-02-11 | Emory University | Novel bone mineralization proteins, dna, vectors, expression systems |
US7923250B2 (en) | 1997-07-30 | 2011-04-12 | Warsaw Orthopedic, Inc. | Methods of expressing LIM mineralization protein in non-osseous cells |
HUP9701554D0 (en) | 1997-09-18 | 1997-11-28 | Human Oltoanyagtermeloe Gyogys | Pharmaceutical composition containing plazma proteins |
US6241762B1 (en) | 1998-03-30 | 2001-06-05 | Conor Medsystems, Inc. | Expandable medical device with ductile hinges |
US7208010B2 (en) | 2000-10-16 | 2007-04-24 | Conor Medsystems, Inc. | Expandable medical device for delivery of beneficial agent |
US7208011B2 (en) | 2001-08-20 | 2007-04-24 | Conor Medsystems, Inc. | Implantable medical device with drug filled holes |
US20040254635A1 (en) | 1998-03-30 | 2004-12-16 | Shanley John F. | Expandable medical device for delivery of beneficial agent |
US6086915A (en) * | 1998-04-01 | 2000-07-11 | Bioresponse L.L.C. | Compositions and methods of adjusting steroid hormone metabolism through phytochemicals |
US6190699B1 (en) | 1998-05-08 | 2001-02-20 | Nzl Corporation | Method of incorporating proteins or peptides into a matrix and administration thereof through mucosa |
WO1999059550A1 (en) | 1998-05-20 | 1999-11-25 | The Liposome Company, Inc. | Novel particulate formulations |
US6221153B1 (en) * | 1998-06-09 | 2001-04-24 | Trevor Percival Castor | Method for producing large crystals of complex molecules |
US7087236B1 (en) * | 1998-09-01 | 2006-08-08 | Merrion Research I Limited | Method for inducing a cell-mediated immune response and improved parenteral vaccine formulations thereof |
US6293967B1 (en) | 1998-10-29 | 2001-09-25 | Conor Medsystems, Inc. | Expandable medical device with ductile hinges |
US20050171594A1 (en) * | 1998-12-31 | 2005-08-04 | Angiotech International Ag | Stent grafts with bioactive coatings |
US20020065546A1 (en) * | 1998-12-31 | 2002-05-30 | Machan Lindsay S. | Stent grafts with bioactive coatings |
US6290673B1 (en) | 1999-05-20 | 2001-09-18 | Conor Medsystems, Inc. | Expandable medical device delivery system and method |
EP1178786A4 (en) * | 1999-05-21 | 2006-03-01 | American Bioscience Inc | Protein stabilized pharmacologically active agents, methods for the preparation thereof and methods for the use thereof |
US7919119B2 (en) * | 1999-05-27 | 2011-04-05 | Acusphere, Inc. | Porous drug matrices and methods of manufacture thereof |
US20020009466A1 (en) * | 1999-08-31 | 2002-01-24 | David J. Brayden | Oral vaccine compositions |
US6656504B1 (en) | 1999-09-09 | 2003-12-02 | Elan Pharma International Ltd. | Nanoparticulate compositions comprising amorphous cyclosporine and methods of making and using such compositions |
US6541508B2 (en) * | 1999-09-13 | 2003-04-01 | Nobex Corporation | Taxane prodrugs |
US6380405B1 (en) | 1999-09-13 | 2002-04-30 | Nobex Corporation | Taxane prodrugs |
US6713454B1 (en) * | 1999-09-13 | 2004-03-30 | Nobex Corporation | Prodrugs of etoposide and etoposide analogs |
WO2001025223A1 (en) | 1999-10-06 | 2001-04-12 | The Research Foundation Of State University Of New York | Stabilization of taxane-containing dispersed systems |
US6638906B1 (en) | 1999-12-13 | 2003-10-28 | Nobex Corporation | Amphiphilic polymers and polypeptide conjugates comprising same |
US20030206958A1 (en) * | 2000-12-22 | 2003-11-06 | Cattaneo Maurizio V. | Chitosan biopolymer for the topical delivery of active agents |
PL350075A1 (en) * | 2000-02-02 | 2002-11-04 | Univ Florida State Res Found | Taxane formulations having improved solubility |
US6749865B2 (en) | 2000-02-15 | 2004-06-15 | Genzyme Corporation | Modification of biopolymers for improved drug delivery |
CA2400172C (en) | 2000-02-28 | 2010-04-20 | Genesegues, Inc. | Nanocapsule encapsulation system and method |
US7674480B2 (en) * | 2000-06-23 | 2010-03-09 | Teva Pharmaceutical Industries Ltd. | Rapidly expanding composition for gastric retention and controlled release of therapeutic agents, and dosage forms including the composition |
US6881420B2 (en) * | 2000-06-23 | 2005-04-19 | Teva Pharmaceutical Industries Ltd. | Compositions and dosage forms for gastric delivery of irinotecan and methods of treatment that use it to inhibit cancer cell proliferation |
US6506408B1 (en) * | 2000-07-13 | 2003-01-14 | Scimed Life Systems, Inc. | Implantable or insertable therapeutic agent delivery device |
US6764507B2 (en) | 2000-10-16 | 2004-07-20 | Conor Medsystems, Inc. | Expandable medical device with improved spatial distribution |
DE20122506U1 (en) | 2000-10-16 | 2005-12-08 | Conor Medsystems, Inc., Menlo Park | Expandable medical device for delivering a beneficial agent |
US8067032B2 (en) * | 2000-12-22 | 2011-11-29 | Baxter International Inc. | Method for preparing submicron particles of antineoplastic agents |
US6951656B2 (en) * | 2000-12-22 | 2005-10-04 | Baxter International Inc. | Microprecipitation method for preparing submicron suspensions |
US20030096013A1 (en) * | 2000-12-22 | 2003-05-22 | Jane Werling | Preparation of submicron sized particles with polymorph control |
US20030072807A1 (en) * | 2000-12-22 | 2003-04-17 | Wong Joseph Chung-Tak | Solid particulate antifungal compositions for pharmaceutical use |
US20040022862A1 (en) * | 2000-12-22 | 2004-02-05 | Kipp James E. | Method for preparing small particles |
US20050048126A1 (en) | 2000-12-22 | 2005-03-03 | Barrett Rabinow | Formulation to render an antimicrobial drug potent against organisms normally considered to be resistant to the drug |
US6977085B2 (en) * | 2000-12-22 | 2005-12-20 | Baxter International Inc. | Method for preparing submicron suspensions with polymorph control |
US6869617B2 (en) * | 2000-12-22 | 2005-03-22 | Baxter International Inc. | Microprecipitation method for preparing submicron suspensions |
US7193084B2 (en) | 2000-12-22 | 2007-03-20 | Baxter International Inc. | Polymorphic form of itraconazole |
US9700866B2 (en) | 2000-12-22 | 2017-07-11 | Baxter International Inc. | Surfactant systems for delivery of organic compounds |
US6884436B2 (en) * | 2000-12-22 | 2005-04-26 | Baxter International Inc. | Method for preparing submicron particle suspensions |
US7115565B2 (en) | 2001-01-18 | 2006-10-03 | Pharmacia & Upjohn Company | Chemotherapeutic microemulsion compositions of paclitaxel with improved oral bioavailability |
US6964680B2 (en) | 2001-02-05 | 2005-11-15 | Conor Medsystems, Inc. | Expandable medical device with tapered hinge |
US20040073294A1 (en) | 2002-09-20 | 2004-04-15 | Conor Medsystems, Inc. | Method and apparatus for loading a beneficial agent into an expandable medical device |
US20020150615A1 (en) * | 2001-02-12 | 2002-10-17 | Howard Sands | Injectable pharmaceutical composition comprising microdroplets of a camptothecin |
US6509027B2 (en) | 2001-02-12 | 2003-01-21 | Supergen, Inc. | Injectable pharmaceutical composition comprising coated particles of camptothecin |
US6497896B2 (en) | 2001-02-12 | 2002-12-24 | Supergen, Inc. | Method for administering camptothecins via injection of a pharmaceutical composition comprising microdroplets containing a camptothecin |
US20040185101A1 (en) * | 2001-03-27 | 2004-09-23 | Macromed, Incorporated. | Biodegradable triblock copolymers as solubilizing agents for drugs and method of use thereof |
US6869618B2 (en) * | 2001-04-10 | 2005-03-22 | Kiel Laboratories, Inc. | Process for preparing tannate liquid and semi-solid dosage forms |
AR033711A1 (en) * | 2001-05-09 | 2004-01-07 | Novartis Ag | PHARMACEUTICAL COMPOSITIONS |
US6797257B2 (en) * | 2001-06-26 | 2004-09-28 | The Board Of Trustees Of The University Of Illinois | Paramagnetic polymerized protein microspheres and methods of preparation thereof |
TWI252847B (en) * | 2001-07-10 | 2006-04-11 | Synta Pharmaceuticals Corp | Synthesis of taxol enhancers |
TWI332943B (en) * | 2001-07-10 | 2010-11-11 | Synta Pharmaceuticals Corp | Taxol enhancer compounds |
TWI297335B (en) | 2001-07-10 | 2008-06-01 | Synta Pharmaceuticals Corp | Taxol enhancer compounds |
US7056338B2 (en) | 2003-03-28 | 2006-06-06 | Conor Medsystems, Inc. | Therapeutic agent delivery device with controlled therapeutic agent release rates |
US20030054042A1 (en) * | 2001-09-14 | 2003-03-20 | Elaine Liversidge | Stabilization of chemical compounds using nanoparticulate formulations |
DE60238422D1 (en) | 2001-09-24 | 2011-01-05 | Boston Scient Ltd | OPTIMIZED DOSAGE IN PACLITAXELIC STENTS |
US20060003012A9 (en) * | 2001-09-26 | 2006-01-05 | Sean Brynjelsen | Preparation of submicron solid particle suspensions by sonication of multiphase systems |
CA2461349C (en) | 2001-09-26 | 2011-11-29 | Baxter International Inc. | Preparation of submicron sized nanoparticles via dispersion and solvent or liquid phase removal |
US20030087837A1 (en) * | 2001-10-15 | 2003-05-08 | Jonas Jeffrey M. | Compositions and methods for delivery of poorly water soluble drugs and methods of treatment |
US7112340B2 (en) * | 2001-10-19 | 2006-09-26 | Baxter International Inc. | Compositions of and method for preparing stable particles in a frozen aqueous matrix |
US20050069549A1 (en) | 2002-01-14 | 2005-03-31 | William Herman | Targeted ligands |
WO2003068159A2 (en) * | 2002-02-11 | 2003-08-21 | Wake Forest University | Compositions and methods for treating pain using cyclooxygenase-1 inhibitors |
JP4842514B2 (en) * | 2002-03-20 | 2011-12-21 | エラン ファーマ インターナショナル,リミティド | Nanoparticle composition of angiogenesis inhibitor |
ITMI20020681A1 (en) * | 2002-03-29 | 2003-09-29 | Acs Dobfar Spa | PROCEDURE FOR THE PRODUCTION OF PACLITAXEL AND ALBUMINA NANOPARTICLES |
ITMI20020680A1 (en) * | 2002-03-29 | 2003-09-29 | Acs Dobfar Spa | IMPROVED ANTI-TUMOR COMPOSITION BASED ON PACLITAXEL AND METHOD FOR ITS OBTAINING |
US20040038303A1 (en) * | 2002-04-08 | 2004-02-26 | Unger Gretchen M. | Biologic modulations with nanoparticles |
US20050069584A1 (en) * | 2002-04-09 | 2005-03-31 | Kiel Jeffrey S | Diphenhydramine tannate solid dose compositions and methods of use |
WO2003090717A1 (en) * | 2002-04-23 | 2003-11-06 | Nanotherapeutics, Inc | Process of forming and modifying particles and compositions produced thereby |
US20040126400A1 (en) * | 2002-05-03 | 2004-07-01 | Iversen Patrick L. | Delivery of therapeutic compounds via microparticles or microbubbles |
PT1509256E (en) * | 2002-05-24 | 2009-10-15 | Angiotech Int Ag | Compositions and methods for coating medical implants |
US8313760B2 (en) | 2002-05-24 | 2012-11-20 | Angiotech International Ag | Compositions and methods for coating medical implants |
US7649023B2 (en) * | 2002-06-11 | 2010-01-19 | Novartis Ag | Biodegradable block copolymeric compositions for drug delivery |
PL206379B1 (en) * | 2002-07-15 | 2010-08-31 | Alcon | Bioerodible film for ophthalmic drug delivery |
CA2497792C (en) | 2002-09-06 | 2014-08-05 | Insert Therapeutics, Inc. | Cyclodextrin-based polymers for therapeutics delivery |
US20040127976A1 (en) * | 2002-09-20 | 2004-07-01 | Conor Medsystems, Inc. | Method and apparatus for loading a beneficial agent into an expandable medical device |
EP1575562B1 (en) * | 2002-11-26 | 2016-10-05 | Seacoast Neurosciene, Inc. | Buoyant polymer particles delivering therapeutic agents |
NZ541142A (en) * | 2002-12-09 | 2008-07-31 | Abraxis Bioscience Inc | Compositions and methods of delivery of pharmacological agents |
EP1581270A2 (en) * | 2002-12-30 | 2005-10-05 | Angiotech International Ag | Silk-containing stent graft |
TWI330079B (en) * | 2003-01-15 | 2010-09-11 | Synta Pharmaceuticals Corp | Treatment for cancers |
US7623908B2 (en) | 2003-01-24 | 2009-11-24 | The Board Of Trustees Of The University Of Illinois | Nonlinear interferometric vibrational imaging |
EP1628656B1 (en) * | 2003-03-25 | 2008-10-15 | Kiel Laboratories, Inc. | Gabapentin tannate in liquid and/or semi-solid dosage forms |
WO2004093866A1 (en) * | 2003-03-25 | 2004-11-04 | Kiel Laboratories, Inc. | Process for preparing phenolic acid salts of gabapentin |
EP1622603A4 (en) * | 2003-03-25 | 2010-03-24 | Kiel Lab Inc | Phenolic acid salts of gabapentin in solid dosage forms and methods of use |
EP1610823B1 (en) | 2003-03-28 | 2011-09-28 | Innovational Holdings, LLC | Implantable medical device with continuous agent concentration gradient |
US20040225022A1 (en) * | 2003-05-09 | 2004-11-11 | Desai Neil P. | Propofol formulation containing reduced oil and surfactants |
US7169179B2 (en) | 2003-06-05 | 2007-01-30 | Conor Medsystems, Inc. | Drug delivery device and method for bi-directional drug delivery |
US7198777B2 (en) * | 2003-06-17 | 2007-04-03 | The Board Of Trustees Of The University Of Illinois | Optical contrast agents for optically modifying incident radiation |
US7217410B2 (en) * | 2003-06-17 | 2007-05-15 | The Board Of Trustees Of The Universtiy Of Illinois | Surface modified protein microparticles |
US8476010B2 (en) | 2003-07-10 | 2013-07-02 | App Pharmaceuticals Llc | Propofol formulations with non-reactive container closures |
US20050181018A1 (en) * | 2003-09-19 | 2005-08-18 | Peyman Gholam A. | Ocular drug delivery |
US7785653B2 (en) | 2003-09-22 | 2010-08-31 | Innovational Holdings Llc | Method and apparatus for loading a beneficial agent into an expandable medical device |
EP1689457A2 (en) * | 2003-11-10 | 2006-08-16 | Angiotech International Ag | Intravascular devices and fibrosis-inducing agents |
WO2005051451A2 (en) * | 2003-11-20 | 2005-06-09 | Angiotech International Ag | Electrical devices and anti-scarring agents |
US7610074B2 (en) * | 2004-01-08 | 2009-10-27 | The Board Of Trustees Of The University Of Illinois | Multi-functional plasmon-resonant contrast agents for optical coherence tomography |
US20050281886A1 (en) * | 2004-05-06 | 2005-12-22 | Ivrea Pharmaceuticals, Inc. | Particles for the delivery of active agents |
US20060141046A1 (en) * | 2004-05-06 | 2006-06-29 | Ivrea Pharmaceuticals, Inc. | Particles for the delivery of active agents |
AU2006249235B2 (en) | 2004-05-14 | 2010-11-11 | Abraxis Bioscience, Llc | Sparc and methods of use thereof |
US20090004277A1 (en) * | 2004-05-18 | 2009-01-01 | Franchini Miriam K | Nanoparticle dispersion containing lactam compound |
AU2005287383B2 (en) * | 2004-05-25 | 2011-09-22 | Chimeros, Inc. | Self-assembling nanoparticle drug delivery system |
BRPI0512526A (en) | 2004-06-23 | 2008-03-11 | Synta Pharmaceuticals Corp | compound, pharmaceutical composition, method for treating a cancer patient and method for preparing a bis (thiohydrazide amide) di-salt |
KR100578382B1 (en) | 2004-07-16 | 2006-05-11 | 나재운 | Water soluble chitosan nanoparticle for delivering a anticance agent and preparing method thereof |
US8557861B2 (en) * | 2004-09-28 | 2013-10-15 | Mast Therapeutics, Inc. | Low oil emulsion compositions for delivering taxoids and other insoluble drugs |
US8415388B2 (en) * | 2005-02-22 | 2013-04-09 | Savvipharm Inc. | Pharmaceutical compositions containing paclitaxel orotate |
US7586618B2 (en) * | 2005-02-28 | 2009-09-08 | The Board Of Trustees Of The University Of Illinois | Distinguishing non-resonant four-wave-mixing noise in coherent stokes and anti-stokes Raman scattering |
AU2005100176A4 (en) * | 2005-03-01 | 2005-04-07 | Gym Tv Pty Ltd | Garbage bin clip |
US7722581B2 (en) * | 2005-04-11 | 2010-05-25 | Gholam A. Peyman | Crystalline lens drug delivery |
US20060229585A1 (en) * | 2005-04-11 | 2006-10-12 | Minu, L.L.C. | Drug delivery to the crystalline lens and other ocular structures |
US7725169B2 (en) * | 2005-04-15 | 2010-05-25 | The Board Of Trustees Of The University Of Illinois | Contrast enhanced spectroscopic optical coherence tomography |
BRPI0610219A2 (en) * | 2005-04-15 | 2010-06-08 | Synta Pharmaceuticals Corp | methods of treating a human being with cancer and pharmaceutical composition |
EP3527202A1 (en) * | 2005-08-31 | 2019-08-21 | Abraxis BioScience, LLC | Compositions and methods for preparation of poorly water soluble drugs with increased stability |
EP2206736B1 (en) | 2005-12-05 | 2012-02-08 | Nitto Denko Corporation | Polyglutamate-amino acid conjugates and methods |
WO2007074476A1 (en) | 2005-12-28 | 2007-07-05 | Dabur Pharma Limited | A biocompatible, non-biodegradable, non-toxic polymer useful for nanoparticle pharmaceutical compositions |
US7787129B2 (en) | 2006-01-31 | 2010-08-31 | The Board Of Trustees Of The University Of Illinois | Method and apparatus for measurement of optical properties in tissue |
TWI376239B (en) * | 2006-02-01 | 2012-11-11 | Andrew Xian Chen | Vitamin e succinate stabilized pharmaceutical compositions, methods for the preparation and the use thereof |
WO2008108776A1 (en) * | 2006-04-07 | 2008-09-12 | Chimeros, Inc. | Compositions and methods for treating b- cell malignancies |
US7458953B2 (en) * | 2006-06-20 | 2008-12-02 | Gholam A. Peyman | Ocular drainage device |
US8728527B2 (en) * | 2006-07-24 | 2014-05-20 | Luminus Biosciences, Inc. | Solid nanoparticle formulation of water insoluble pharmaceutical substances with reduced ostwald ripening |
JP2010501562A (en) | 2006-08-21 | 2010-01-21 | シンタ ファーマシューティカルズ コーポレーション | Compounds for treating proliferative disorders |
US20100055459A1 (en) * | 2006-08-30 | 2010-03-04 | Liquidia Technologies, Inc. | Nanoparticles Having Functional Additives for Self and Directed Assembly and Methods of Fabricating Same |
US20080280987A1 (en) * | 2006-08-31 | 2008-11-13 | Desai Neil P | Methods of inhibiting angiogenesis and treating angiogenesis-associated diseases |
WO2008027445A2 (en) * | 2006-08-31 | 2008-03-06 | Synta Pharmaceuticals Corp. | Combination with bis(thiohydrazide amides) for treating cancer |
US9498528B2 (en) * | 2006-09-13 | 2016-11-22 | Genzyme Corporation | Treatment of multiple sclerosis (MS) |
AR063704A1 (en) | 2006-09-14 | 2009-02-11 | Makhteshim Chem Works Ltd | PESTICIDE NANOPARTICLES OBTAINED OBTAINED FROM MICROEMULSIONS AND NANOEMULSIONS |
US20110021592A1 (en) * | 2006-09-14 | 2011-01-27 | Shlomo Magdassi | Organic nanoparticles obtained from microemulsions by solvent evaporation |
US20080176958A1 (en) | 2007-01-24 | 2008-07-24 | Insert Therapeutics, Inc. | Cyclodextrin-based polymers for therapeutics delivery |
US20080181852A1 (en) * | 2007-01-29 | 2008-07-31 | Nitto Denko Corporation | Multi-functional Drug Carriers |
EP2144600A4 (en) * | 2007-04-04 | 2011-03-16 | Massachusetts Inst Technology | Poly (amino acid) targeting moieties |
AU2008236566A1 (en) * | 2007-04-09 | 2008-10-16 | Chimeros, Inc. | Self-assembling nanoparticle drug delivery system |
CN104800856A (en) * | 2007-04-10 | 2015-07-29 | 日东电工株式会社 | Multi-functional polyglutamate drug carriers |
EP2155255B1 (en) | 2007-05-09 | 2013-08-14 | Nitto Denko Corporation | Compositions that include a hydrophobic compound and a polyamino acid conjugate |
US8426467B2 (en) | 2007-05-22 | 2013-04-23 | Baxter International Inc. | Colored esmolol concentrate |
US8722736B2 (en) | 2007-05-22 | 2014-05-13 | Baxter International Inc. | Multi-dose concentrate esmolol with benzyl alcohol |
DK2644192T3 (en) | 2007-09-28 | 2017-06-26 | Pfizer | Cancer cell targeting using nanoparticles |
US7751057B2 (en) | 2008-01-18 | 2010-07-06 | The Board Of Trustees Of The University Of Illinois | Magnetomotive optical coherence tomography |
US8983580B2 (en) | 2008-01-18 | 2015-03-17 | The Board Of Trustees Of The University Of Illinois | Low-coherence interferometry and optical coherence tomography for image-guided surgical treatment of solid tumors |
US8115934B2 (en) | 2008-01-18 | 2012-02-14 | The Board Of Trustees Of The University Of Illinois | Device and method for imaging the ear using optical coherence tomography |
AU2009222230A1 (en) * | 2008-03-06 | 2009-09-11 | Nitto Denko Corporation | Polymer paclitaxel conjugates and methods for treating cancer |
TWI541020B (en) | 2008-04-17 | 2016-07-11 | 巴克斯歐塔公司 | Biologically active peptides |
KR101977846B1 (en) | 2008-12-19 | 2019-05-14 | 박스알타 인코퍼레이티드 | Tfpi inhibitors and methods of use |
WO2010120874A2 (en) | 2009-04-14 | 2010-10-21 | Chimeros, Inc. | Chimeric therapeutics, compositions, and methods for using same |
WO2011017835A1 (en) | 2009-08-11 | 2011-02-17 | Nanjing University | Preparation method of protein or peptide nanoparticles for in vivo drug delivery by unfolding and refolding |
WO2011062614A1 (en) * | 2009-11-20 | 2011-05-26 | Tonix Pharmaceuticals, Inc. | Methods and compositions for treating symptoms associated with post-traumatic stress disorder using cyclobenzaprine |
JP6220126B2 (en) * | 2009-11-23 | 2017-10-25 | セルリアン・ファーマ・インコーポレイテッド | Polymers based on cyclodextrins for therapeutic delivery |
EP2531173B1 (en) * | 2010-02-03 | 2018-09-26 | Oncbiomune, L.L.C. | Taxane- and taxoid-protein compositions |
TWI438009B (en) * | 2010-02-19 | 2014-05-21 | Teikoku Pharma Usa Inc | Taxane pro-emulsion formulations and methods making and using the same |
CN103025345B (en) | 2010-03-19 | 2016-01-20 | 巴克斯特国际公司 | TFPI inhibitor and using method |
ES2652509T3 (en) | 2010-05-03 | 2018-02-02 | Teikoku Pharma Usa, Inc. | Non-aqueous taxane proemulsion formulations and methods for preparing and using them |
US20110319389A1 (en) | 2010-06-24 | 2011-12-29 | Tonix Pharmaceuticals, Inc. | Methods and compositions for treating fatigue associated with disordered sleep using very low dose cyclobenzaprine |
KR101130754B1 (en) | 2010-06-25 | 2012-03-28 | 제일약품주식회사 | Pharmaceutical compositions having improved solubility of poorly soluble tricyclic derivative compounds |
TW201242974A (en) | 2010-11-30 | 2012-11-01 | Gilead Pharmasset Llc | Compounds |
LT2694056T (en) | 2011-04-01 | 2019-12-10 | Astrazeneca Ab | Therapeutic treatment |
SG10201606406PA (en) | 2011-04-28 | 2016-09-29 | Abraxis Bioscience Llc | Intravascular delivery of nanoparticle compositions and uses thereof |
CA2838387A1 (en) | 2011-06-06 | 2012-12-13 | Chevron Phillips Chemical Company Lp | Use of metallocene compounds for cancer treatment |
CA2838833A1 (en) | 2011-06-10 | 2012-12-13 | Biogen Idec Ma Inc. | Pro-coagulant compounds and methods of use thereof |
JP2014527072A (en) | 2011-09-09 | 2014-10-09 | バイオメド リアルティー, エル.ピー. | Methods and compositions for controlling the assembly of viral proteins |
JP6309454B2 (en) | 2011-11-30 | 2018-04-11 | アストラゼネカ アクチボラグ | Combined cancer treatment |
WO2013084207A1 (en) | 2011-12-07 | 2013-06-13 | Universidade Do Minho | Formulations for micelle formation comprising a protein and methods preparation thereof |
KR101455921B1 (en) * | 2012-01-30 | 2014-11-12 | 성균관대학교산학협력단 | Albumin nanoparticles containing poorly water soluble drugs and its preparation method and application thereof |
WO2013141965A1 (en) | 2012-03-21 | 2013-09-26 | Baxter International Inc. | Tfpi inhibitors and methods of use |
LT2833905T (en) | 2012-04-04 | 2018-07-10 | Halozyme, Inc. | Combination therapy with hyaluronidase and a tumor-targeted taxane |
AU2013204533B2 (en) | 2012-04-17 | 2017-02-02 | Astrazeneca Ab | Crystalline forms |
AU2013270682A1 (en) | 2012-06-08 | 2014-12-11 | Biogen Ma Inc. | Procoagulant compounds |
CN102784109B (en) * | 2012-08-22 | 2014-08-06 | 复旦大学 | Taxane medicines albumin nanoparticle preparation for injection and preparation method thereof |
JO3685B1 (en) | 2012-10-01 | 2020-08-27 | Teikoku Pharma Usa Inc | Non-aqueous taxane nanodispersion formulations and methods of using the same |
US20140094432A1 (en) | 2012-10-02 | 2014-04-03 | Cerulean Pharma Inc. | Methods and systems for polymer precipitation and generation of particles |
CA2892227C (en) | 2012-11-30 | 2020-12-15 | Novomedix, Llc | Substituted biaryl sulfonamides and the use thereof |
PT106738B (en) * | 2013-01-09 | 2015-06-08 | Hovione Farmaciencia Sa | METHOD FOR THE CONTROL OF OSTWALD DIFUSIONAL DEGRADATION PHENOMENON (OSTWALD RIPENING) IN THE PROCESSING OF PARTICLES OF A PHARMACEUTICAL INGREDIENT |
US9511046B2 (en) | 2013-01-11 | 2016-12-06 | Abraxis Bioscience, Llc | Methods of treating pancreatic cancer |
CN105142629B (en) | 2013-03-04 | 2018-11-23 | 阿斯利康(瑞典)有限公司 | It is treated in combination |
WO2014145156A2 (en) | 2013-03-15 | 2014-09-18 | Tonix Pharmaceuticals, Inc. | Eutectic formulations of cyclobenzaprine hydrochloride and amitriptyline hydrochloride |
EP3024490A1 (en) | 2013-07-26 | 2016-06-01 | Threshold Pharmaceuticals, Inc. | Treatment of pancreatic cancer with a combination of a hypoxia-acti vated prodrug and a taxane |
US10064940B2 (en) | 2013-12-11 | 2018-09-04 | Siva Therapeutics Inc. | Multifunctional radiation delivery apparatus and method |
WO2015119976A1 (en) * | 2014-02-04 | 2015-08-13 | Abbott Cardiovascular Systems Inc. | Modified pla polymer and method of making and using |
CN106170307B (en) | 2014-02-14 | 2020-07-28 | 波士顿科学国际有限公司 | Rapidly degrading embolic particles with therapeutic agent release |
WO2015018380A2 (en) | 2014-07-03 | 2015-02-12 | Cspc Zhongqi Pharmaceutical Technology(Shijiazhuang)Co., Ltd. | Therapeutic nanoparticles and the preparation methods thereof |
SG10201902499VA (en) | 2014-09-03 | 2019-04-29 | Genesegues Inc | Therapeutic nanoparticles and related compositions, methods and systems |
BR112017005231A2 (en) | 2014-09-18 | 2018-03-13 | Tonix Pharma Holdings Ltd | eutectic formulations of cyclobenzaprine hydrochloride |
US10052394B2 (en) | 2014-11-21 | 2018-08-21 | General Electric Company | Microbubble tether for diagnostic and therapeutic applications |
EP3615011A4 (en) * | 2017-04-24 | 2021-01-06 | ZY Therapeutics Inc. | Pharmaceutical composition for in vivo delivery, method of preparation of a substantially waterinsoluble pharmacologically active agent |
IL275289B2 (en) | 2017-12-11 | 2024-01-01 | Tonix Pharma Holdings Ltd | Cyclobenzaprine treatment for agitation, psychosis and cognitive decline in dementia and neurodegenerative conditions |
TWI660728B (en) | 2018-02-09 | 2019-06-01 | 國立交通大學 | Quinazolinamine derivatives and pharmaceutical compositions and uses thereof |
US20190351031A1 (en) | 2018-05-16 | 2019-11-21 | Halozyme, Inc. | Methods of selecting subjects for combination cancer therapy with a polymer-conjugated soluble ph20 |
WO2020047766A1 (en) * | 2018-09-05 | 2020-03-12 | Jmd Innovation Inc. | Position marker and delivery system |
WO2020114615A1 (en) | 2018-12-07 | 2020-06-11 | Baxalta GmbH | Bispecific antibodies binding factor ixa and factor x |
WO2020115283A1 (en) | 2018-12-07 | 2020-06-11 | Baxalta GmbH | Bispecific antibodies binding factor ixa and factor x |
US11298336B2 (en) * | 2019-05-30 | 2022-04-12 | Soluble Technologies, Inc. | Water soluble formulation |
US11786475B2 (en) | 2020-07-22 | 2023-10-17 | Soluble Technologies Inc. | Film-based dosage form |
EP4035655A1 (en) | 2021-02-01 | 2022-08-03 | Oxford University Innovation Limited | Immune modulating particles |
EP4036580A1 (en) | 2021-02-01 | 2022-08-03 | Oxford University Innovation Limited | Drug loaded cavitation agent |
EP4035673A1 (en) | 2021-02-01 | 2022-08-03 | Oxford University Innovation Limited | Transdermal vaccine |
EP4036581A1 (en) | 2021-02-01 | 2022-08-03 | Oxford University Innovation Limited | Cavitation agent |
EP4035676A1 (en) | 2021-02-01 | 2022-08-03 | Oxford University Innovation Limited | Vaccine compositions |
CN114159554B (en) * | 2021-11-22 | 2022-12-13 | 广州优理氏生物科技有限公司 | Preparation method and application of fibronectin-polyvinyl alcohol microspheres |
WO2023194441A1 (en) | 2022-04-05 | 2023-10-12 | Istituto Nazionale Tumori Irccs - Fondazione G. Pascale | Combination of hdac inhibitors and statins for use in the treatment of pancreatic cancer |
WO2024046999A1 (en) * | 2022-08-31 | 2024-03-07 | Johann Wolfgang Goethe-Universität Frankfurt am Main | Lecithin-modified nanoscale oxygen carriers (lenox) |
Citations (73)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4534899A (en) * | 1981-07-20 | 1985-08-13 | Lipid Specialties, Inc. | Synthetic phospholipid compounds |
US5059699A (en) * | 1990-08-28 | 1991-10-22 | Virginia Tech Intellectual Properties, Inc. | Water soluble derivatives of taxol |
US5362478A (en) * | 1993-03-26 | 1994-11-08 | Vivorx Pharmaceuticals, Inc. | Magnetic resonance imaging with fluorocarbons encapsulated in a cross-linked polymeric shell |
US5399363A (en) * | 1991-01-25 | 1995-03-21 | Eastman Kodak Company | Surface modified anticancer nanoparticles |
US5407683A (en) * | 1990-06-01 | 1995-04-18 | Research Corporation Technologies, Inc. | Pharmaceutical solutions and emulsions containing taxol |
US5415869A (en) * | 1993-11-12 | 1995-05-16 | The Research Foundation Of State University Of New York | Taxol formulation |
US5424073A (en) * | 1992-03-23 | 1995-06-13 | Georgetown University | Liposome encapsulated taxol and a method of using the same |
US5440056A (en) * | 1992-04-17 | 1995-08-08 | Abbott Laboratories | 9-deoxotaxane compounds |
US5439686A (en) * | 1993-02-22 | 1995-08-08 | Vivorx Pharmaceuticals, Inc. | Methods for in vivo delivery of substantially water insoluble pharmacologically active agents and compositions useful therefor |
US5498421A (en) * | 1993-02-22 | 1996-03-12 | Vivorx Pharmaceuticals, Inc. | Composition useful for in vivo delivery of biologics and methods employing same |
US5565478A (en) * | 1994-03-14 | 1996-10-15 | The United States Of America As Represented By The Department Of Health & Human Services | Combination therapy using signal transduction inhibitors with paclitaxel and other taxane analogs |
US5567434A (en) * | 1989-03-31 | 1996-10-22 | The Regents Of The University Of California | Preparation of liposome and lipid complex compositions |
US5616330A (en) * | 1994-07-19 | 1997-04-01 | Hemagen/Pfc | Stable oil-in-water emulsions incorporating a taxine (taxol) and method of making same |
US5616608A (en) * | 1993-07-29 | 1997-04-01 | The United States Of America As Represented By The Department Of Health And Human Services | Method of treating atherosclerosis or restenosis using microtubule stabilizing agent |
US5626862A (en) * | 1994-08-02 | 1997-05-06 | Massachusetts Institute Of Technology | Controlled local delivery of chemotherapeutic agents for treating solid tumors |
US5626867A (en) * | 1992-03-17 | 1997-05-06 | Max-Planck Gesellschaft Zur Forderung Der Wissenschaften E.V. | Liposomes with a negative excess charge |
US5650156A (en) * | 1993-02-22 | 1997-07-22 | Vivorx Pharmaceuticals, Inc. | Methods for in vivo delivery of nutriceuticals and compositions useful therefor |
US5665383A (en) * | 1993-02-22 | 1997-09-09 | Vivorx Pharmaceuticals, Inc. | Methods for the preparation of immunostimulating agents for in vivo delivery |
US5665382A (en) * | 1993-02-22 | 1997-09-09 | Vivorx Pharmaceuticals, Inc. | Methods for the preparation of pharmaceutically active agents for in vivo delivery |
US5670536A (en) * | 1994-04-25 | 1997-09-23 | Rhone-Poulenc Rorer S.A. | Pharmaceutical composition based on taxoids |
US5681846A (en) * | 1995-03-17 | 1997-10-28 | Board Of Regents, The University Of Texas System | Extended stability formulations for paclitaxel |
US5716981A (en) * | 1993-07-19 | 1998-02-10 | Angiogenesis Technologies, Inc. | Anti-angiogenic compositions and methods of use |
US5725804A (en) * | 1991-01-15 | 1998-03-10 | Hemosphere, Inc. | Non-crosslinked protein particles for therapeutic and diagnostic use |
US5731334A (en) * | 1994-01-11 | 1998-03-24 | The Scripps Research Institute | Method for treating cancer using taxoid onium salt prodrugs |
US5733925A (en) * | 1993-01-28 | 1998-03-31 | Neorx Corporation | Therapeutic inhibitor of vascular smooth muscle cells |
US5756537A (en) * | 1996-11-08 | 1998-05-26 | Parkash S. Gill, M.D., Inc. | Regime for paclitaxel in Kaposi's sarcoma patients |
US5766635A (en) * | 1991-06-28 | 1998-06-16 | Rhone-Poulenc Rorer S.A. | Process for preparing nanoparticles |
US5795909A (en) * | 1996-05-22 | 1998-08-18 | Neuromedica, Inc. | DHA-pharmaceutical agent conjugates of taxanes |
US5916596A (en) * | 1993-02-22 | 1999-06-29 | Vivorx Pharmaceuticals, Inc. | Protein stabilized pharmacologically active agents, methods for the preparation thereof and methods for the use thereof |
US5928669A (en) * | 1992-07-28 | 1999-07-27 | Danbiosyst Uk Limited | Lymphatic delivery methods |
US5945033A (en) * | 1991-01-15 | 1999-08-31 | Hemosphere, Inc. | Method for making non-crosslinked protein particles for therapeutic and diagnostic use |
US6051600A (en) * | 1995-09-12 | 2000-04-18 | Mayhew; Eric | Liposomal hydrolysis-promoting hydrophobic taxane derivatives |
US6066668A (en) * | 1994-11-14 | 2000-05-23 | Bionumerik Pharmaceuticals, Inc. | Formulations and methods of reducing toxicity of antineoplastic agents |
US6090925A (en) * | 1993-03-09 | 2000-07-18 | Epic Therapeutics, Inc. | Macromolecular microparticles and methods of production and use |
US6096331A (en) * | 1993-02-22 | 2000-08-01 | Vivorx Pharmaceuticals, Inc. | Methods and compositions useful for administration of chemotherapeutic agents |
US6107332A (en) * | 1995-09-12 | 2000-08-22 | The Liposome Company, Inc. | Hydrolysis-promoting hydrophobic taxane derivatives |
US6120805A (en) * | 1990-04-06 | 2000-09-19 | Rhone-Poulenc Rorer Sa | Microspheres, process for their preparation and their use |
US6179817B1 (en) * | 1995-02-22 | 2001-01-30 | Boston Scientific Corporation | Hybrid coating for medical devices |
US6197051B1 (en) * | 1997-06-18 | 2001-03-06 | Boston Scientific Corporation | Polycarbonate-polyurethane dispersions for thromobo-resistant coatings |
US6197349B1 (en) * | 1993-08-12 | 2001-03-06 | Knoll Aktiengesellschaft | Particles with modified physicochemical properties, their preparation and uses |
US6306421B1 (en) * | 1992-09-25 | 2001-10-23 | Neorx Corporation | Therapeutic inhibitor of vascular smooth muscle cells |
US6432928B1 (en) * | 1994-11-11 | 2002-08-13 | Chinoin Gyogyszer Es Vegyeszeti Termekek Gyara Rt. | Complexes and their compositions |
US6441025B2 (en) * | 1996-03-12 | 2002-08-27 | Pg-Txl Company, L.P. | Water soluble paclitaxel derivatives |
US6458373B1 (en) * | 1997-01-07 | 2002-10-01 | Sonus Pharmaceuticals, Inc. | Emulsion vehicle for poorly soluble drugs |
US6528067B1 (en) * | 1993-02-22 | 2003-03-04 | American Bioscience, Inc. | Total nutrient admixtures as stable multicomponent liquids or dry powders and methods for the preparation thereof |
US6537579B1 (en) * | 1993-02-22 | 2003-03-25 | American Bioscience, Inc. | Compositions and methods for administration of pharmacologically active compounds |
US20030087985A1 (en) * | 1990-10-15 | 2003-05-08 | Hubbell Jeffrey A. | Gels for encapsulation of biological materials |
US6565842B1 (en) * | 1995-06-07 | 2003-05-20 | American Bioscience, Inc. | Crosslinkable polypeptide compositions |
US6610735B2 (en) * | 1995-10-26 | 2003-08-26 | Baker Norton Pharmaceuticals, Inc. | Method, compositions and kits for increasing the oral bioavailability of pharmaceutical agents |
US20030199425A1 (en) * | 1997-06-27 | 2003-10-23 | Desai Neil P. | Compositions and methods for treatment of hyperplasia |
US6743826B1 (en) * | 1997-09-18 | 2004-06-01 | Human Rt | Pharmaceutical compositions containing plasma protein |
US6749868B1 (en) * | 1993-02-22 | 2004-06-15 | American Bioscience, Inc. | Protein stabilized pharmacologically active agents, methods for the preparation thereof and methods for the use thereof |
US6753006B1 (en) * | 1993-02-22 | 2004-06-22 | American Bioscience, Inc. | Paclitaxel-containing formulations |
US6759431B2 (en) * | 1996-05-24 | 2004-07-06 | Angiotech Pharmaceuticals, Inc. | Compositions and methods for treating or preventing diseases of body passageways |
US20050004002A1 (en) * | 2002-12-09 | 2005-01-06 | American Bioscience, Inc. | Compositions and methods of delivery of pharmacological agents |
US20060073175A1 (en) * | 1993-02-22 | 2006-04-06 | American Bioscience, Inc. | Methods and formulations for delivery of pharmacologically active agents |
US20070082838A1 (en) * | 2005-08-31 | 2007-04-12 | Abraxis Bioscience, Inc. | Compositions and methods for preparation of poorly water soluble drugs with increased stability |
US20070087022A1 (en) * | 1996-10-01 | 2007-04-19 | Abraxis Bioscience, Inc. | Novel formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof |
US20070093547A1 (en) * | 1997-06-27 | 2007-04-26 | Desai Neil P | Novel formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof |
US20070117133A1 (en) * | 2004-05-14 | 2007-05-24 | Abraxis Bioscience, Inc. | Sparc and methods of use thereof |
US20070116774A1 (en) * | 2005-02-18 | 2007-05-24 | Abraxis Bioscience, Inc. | Methods and compositions for treating proliferative diseases |
US20070117744A1 (en) * | 2005-08-31 | 2007-05-24 | Desai Neil P | Compositions comprising poorly water soluble pharmaceutical agents and antimicrobial agents |
US7238369B2 (en) * | 1997-03-12 | 2007-07-03 | The Regents Of The University Of California | Cationic liposome delivery of taxanes to angiogenic blood vessels |
US20070166388A1 (en) * | 2005-02-18 | 2007-07-19 | Desai Neil P | Combinations and modes of administration of therapeutic agents and combination therapy |
US7332568B2 (en) * | 2005-02-18 | 2008-02-19 | Abraxis Bioscience, Inc. | Q3 SPARC deletion mutant and uses thereof |
US20080161382A1 (en) * | 1993-02-22 | 2008-07-03 | Neil Desai | Novel formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof |
US20090263483A1 (en) * | 2008-04-10 | 2009-10-22 | Desai Neil P | Nanoparticle formulations and uses thereof |
US20100035800A1 (en) * | 1993-02-22 | 2010-02-11 | Desai Neil P | Novel formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof |
US20100048499A1 (en) * | 2006-12-14 | 2010-02-25 | Desai Neil P | Breast cancer therapy based on hormone receptor status with nanoparticles comprising taxane |
US20100112077A1 (en) * | 2006-11-06 | 2010-05-06 | Abraxis Bioscience, Llc | Nanoparticles of paclitaxel and albumin in combination with bevacizumab against cancer |
US20100166869A1 (en) * | 2007-05-03 | 2010-07-01 | Desai Neil P | Methods and compositions for treating pulmonary hypertension |
US20100183728A1 (en) * | 2007-03-07 | 2010-07-22 | Desai Neil P | Nanoparticle comprising rapamycin and albumin as anticancer agent |
US20100215751A1 (en) * | 2007-06-01 | 2010-08-26 | Desai Neil P | Methods and compositions for treating recurrent cancer |
Family Cites Families (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3526074A (en) * | 1969-03-17 | 1970-09-01 | Stanley Works | Serpentine cross section frame assembly |
US3959457A (en) * | 1970-06-05 | 1976-05-25 | Temple University | Microparticulate material and method of making such material |
US4073943A (en) * | 1974-09-11 | 1978-02-14 | Apoteksvarucentralen Vitrum Ab | Method of enhancing the administration of pharmalogically active agents |
US4247406A (en) * | 1979-04-23 | 1981-01-27 | Widder Kenneth J | Intravascularly-administrable, magnetically-localizable biodegradable carrier |
US4572203A (en) * | 1983-01-27 | 1986-02-25 | Feinstein Steven B | Contact agents for ultrasonic imaging |
US4718433A (en) * | 1983-01-27 | 1988-01-12 | Feinstein Steven B | Contrast agents for ultrasonic imaging |
US4622219A (en) * | 1983-06-17 | 1986-11-11 | Haynes Duncan H | Method of inducing local anesthesia using microdroplets of a general anesthetic |
DE3376660D1 (en) * | 1983-06-22 | 1988-06-23 | Stolle Res & Dev | Encapsulated cells, their method of preparation and use |
US4671954A (en) * | 1983-12-13 | 1987-06-09 | University Of Florida | Microspheres for incorporation of therapeutic substances and methods of preparation thereof |
CA1215922A (en) * | 1984-05-25 | 1986-12-30 | Connaught Laboratories Limited | Microencapsulation of living tissue and cells |
US4753788A (en) * | 1985-01-31 | 1988-06-28 | Vestar Research Inc. | Method for preparing small vesicles using microemulsification |
SE459005B (en) * | 1985-07-12 | 1989-05-29 | Aake Rikard Lindahl | SET TO MANUFACTURE SPHERICAL POLYMER PARTICLES |
US5023271A (en) * | 1985-08-13 | 1991-06-11 | California Biotechnology Inc. | Pharmaceutical microemulsions |
KR950014441B1 (en) * | 1986-08-28 | 1995-11-28 | 코르텍스 리미티드 | Microgranular preparation useful in the delivery of biologically active materials to the intestinal regions of animals |
US4925678A (en) * | 1987-04-01 | 1990-05-15 | Ranney David F | Endothelial envelopment drug carriers |
IE59934B1 (en) * | 1987-06-19 | 1994-05-04 | Elan Corp Plc | Liquid suspension for oral administration |
SE8704158L (en) * | 1987-10-26 | 1989-04-27 | Carbomatrix Ab C O Ulf Schroed | MICROSPHERE, PROCEDURES FOR PREPARING IT AND USING THEREOF |
US4844882A (en) * | 1987-12-29 | 1989-07-04 | Molecular Biosystems, Inc. | Concentrated stabilized microbubble-type ultrasonic imaging agent |
US4929446A (en) * | 1988-04-19 | 1990-05-29 | American Cyanamid Company | Unit dosage form |
NO176278C (en) * | 1988-08-24 | 1995-03-08 | Allied Colloids Ltd | Process for the preparation of a particulate mixture of active ingredient in a polymeric material |
US5026559A (en) * | 1989-04-03 | 1991-06-25 | Kinaform Technology, Inc. | Sustained-release pharmaceutical preparation |
CA2030551C (en) * | 1989-05-01 | 1998-08-25 | Wayne Gombotz | Process for producing small particles of biologically active molecules |
US5019400A (en) * | 1989-05-01 | 1991-05-28 | Enzytech, Inc. | Very low temperature casting of controlled release microspheres |
FR2651680B1 (en) * | 1989-09-14 | 1991-12-27 | Medgenix Group Sa | NOVEL PROCESS FOR THE PREPARATION OF LIPID MICROPARTICLES. |
WO1991015947A1 (en) * | 1990-04-17 | 1991-10-31 | Isp Investments Inc. | Preparation of discrete microdroplets of an oil in water stabilized by in situ polymerization of a water-soluble vinyl monomer |
US5110606A (en) * | 1990-11-13 | 1992-05-05 | Affinity Biotech, Inc. | Non-aqueous microemulsions for drug delivery |
US5370901A (en) * | 1991-02-15 | 1994-12-06 | Bracco International B.V. | Compositions for increasing the image contrast in diagnostic investigations of the digestive tract of patients |
US5344640A (en) * | 1991-10-22 | 1994-09-06 | Mallinckrodt Medical, Inc. | Preparation of apatite particles for medical diagnostic imaging |
-
1993
- 1993-02-22 US US08/023,698 patent/US5439686A/en not_active Expired - Lifetime
-
1994
- 1994-02-22 CN CN2006100012790A patent/CN1839806B/en not_active Expired - Lifetime
-
1995
- 1995-03-29 US US08/412,726 patent/US5560933A/en not_active Expired - Lifetime
-
2010
- 2010-02-25 US US12/713,092 patent/US20110052708A1/en not_active Abandoned
Patent Citations (98)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4534899A (en) * | 1981-07-20 | 1985-08-13 | Lipid Specialties, Inc. | Synthetic phospholipid compounds |
US5567434A (en) * | 1989-03-31 | 1996-10-22 | The Regents Of The University Of California | Preparation of liposome and lipid complex compositions |
US6120805A (en) * | 1990-04-06 | 2000-09-19 | Rhone-Poulenc Rorer Sa | Microspheres, process for their preparation and their use |
US5407683A (en) * | 1990-06-01 | 1995-04-18 | Research Corporation Technologies, Inc. | Pharmaceutical solutions and emulsions containing taxol |
US5059699A (en) * | 1990-08-28 | 1991-10-22 | Virginia Tech Intellectual Properties, Inc. | Water soluble derivatives of taxol |
US20030087985A1 (en) * | 1990-10-15 | 2003-05-08 | Hubbell Jeffrey A. | Gels for encapsulation of biological materials |
US5725804A (en) * | 1991-01-15 | 1998-03-10 | Hemosphere, Inc. | Non-crosslinked protein particles for therapeutic and diagnostic use |
US5945033A (en) * | 1991-01-15 | 1999-08-31 | Hemosphere, Inc. | Method for making non-crosslinked protein particles for therapeutic and diagnostic use |
US5399363A (en) * | 1991-01-25 | 1995-03-21 | Eastman Kodak Company | Surface modified anticancer nanoparticles |
US5766635A (en) * | 1991-06-28 | 1998-06-16 | Rhone-Poulenc Rorer S.A. | Process for preparing nanoparticles |
US6074659A (en) * | 1991-09-27 | 2000-06-13 | Noerx Corporation | Therapeutic inhibitor of vascular smooth muscle cells |
US6268390B1 (en) * | 1991-09-27 | 2001-07-31 | Neorx Corporation | Therapeutic inhibitor of vascular smooth muscle cells |
US5626867A (en) * | 1992-03-17 | 1997-05-06 | Max-Planck Gesellschaft Zur Forderung Der Wissenschaften E.V. | Liposomes with a negative excess charge |
US5648090A (en) * | 1992-03-23 | 1997-07-15 | Georgetown University | Liposome encapsulated toxol and a method of using the same |
US5424073A (en) * | 1992-03-23 | 1995-06-13 | Georgetown University | Liposome encapsulated taxol and a method of using the same |
US5440056A (en) * | 1992-04-17 | 1995-08-08 | Abbott Laboratories | 9-deoxotaxane compounds |
US5928669A (en) * | 1992-07-28 | 1999-07-27 | Danbiosyst Uk Limited | Lymphatic delivery methods |
US6306421B1 (en) * | 1992-09-25 | 2001-10-23 | Neorx Corporation | Therapeutic inhibitor of vascular smooth muscle cells |
US5811447A (en) * | 1993-01-28 | 1998-09-22 | Neorx Corporation | Therapeutic inhibitor of vascular smooth muscle cells |
US5733925A (en) * | 1993-01-28 | 1998-03-31 | Neorx Corporation | Therapeutic inhibitor of vascular smooth muscle cells |
US6753006B1 (en) * | 1993-02-22 | 2004-06-22 | American Bioscience, Inc. | Paclitaxel-containing formulations |
US5439686A (en) * | 1993-02-22 | 1995-08-08 | Vivorx Pharmaceuticals, Inc. | Methods for in vivo delivery of substantially water insoluble pharmacologically active agents and compositions useful therefor |
US5635207A (en) * | 1993-02-22 | 1997-06-03 | Vivorx Pharmaceuticals, Inc. | Methods for the preparation of blood substitutes for in vivo delivery |
US5650156A (en) * | 1993-02-22 | 1997-07-22 | Vivorx Pharmaceuticals, Inc. | Methods for in vivo delivery of nutriceuticals and compositions useful therefor |
US6528067B1 (en) * | 1993-02-22 | 2003-03-04 | American Bioscience, Inc. | Total nutrient admixtures as stable multicomponent liquids or dry powders and methods for the preparation thereof |
US5665383A (en) * | 1993-02-22 | 1997-09-09 | Vivorx Pharmaceuticals, Inc. | Methods for the preparation of immunostimulating agents for in vivo delivery |
US5665382A (en) * | 1993-02-22 | 1997-09-09 | Vivorx Pharmaceuticals, Inc. | Methods for the preparation of pharmaceutically active agents for in vivo delivery |
US6537579B1 (en) * | 1993-02-22 | 2003-03-25 | American Bioscience, Inc. | Compositions and methods for administration of pharmacologically active compounds |
US20100035800A1 (en) * | 1993-02-22 | 2010-02-11 | Desai Neil P | Novel formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof |
US5639473A (en) * | 1993-02-22 | 1997-06-17 | Vivorx Pharmaceuticals, Inc. | Methods for the preparation of nucleic acids for in vivo delivery |
US6506405B1 (en) * | 1993-02-22 | 2003-01-14 | American Bioscience, Inc. | Methods and formulations of cremophor-free taxanes |
US5560933A (en) * | 1993-02-22 | 1996-10-01 | Vivorx Pharmaceuticals, Inc. | Methods for in vivo delivery of substantially water insoluble pharmacologically active agents and compositions useful therefor |
US5498421A (en) * | 1993-02-22 | 1996-03-12 | Vivorx Pharmaceuticals, Inc. | Composition useful for in vivo delivery of biologics and methods employing same |
US20080161382A1 (en) * | 1993-02-22 | 2008-07-03 | Neil Desai | Novel formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof |
US5916596A (en) * | 1993-02-22 | 1999-06-29 | Vivorx Pharmaceuticals, Inc. | Protein stabilized pharmacologically active agents, methods for the preparation thereof and methods for the use thereof |
US20060073175A1 (en) * | 1993-02-22 | 2006-04-06 | American Bioscience, Inc. | Methods and formulations for delivery of pharmacologically active agents |
US6749868B1 (en) * | 1993-02-22 | 2004-06-15 | American Bioscience, Inc. | Protein stabilized pharmacologically active agents, methods for the preparation thereof and methods for the use thereof |
US6096331A (en) * | 1993-02-22 | 2000-08-01 | Vivorx Pharmaceuticals, Inc. | Methods and compositions useful for administration of chemotherapeutic agents |
US6090925A (en) * | 1993-03-09 | 2000-07-18 | Epic Therapeutics, Inc. | Macromolecular microparticles and methods of production and use |
US5505932A (en) * | 1993-03-26 | 1996-04-09 | Vivorx Pharmaceuticals, Inc. | Method for the preparation of fluorocarbon-containing polymeric shells for medical imaging |
US5508021A (en) * | 1993-03-26 | 1996-04-16 | Vivorx Pharmaceuticals, Inc. | Non-fluorinated polymeric shells for medical imaging |
US5512268A (en) * | 1993-03-26 | 1996-04-30 | Vivorx Pharmaceuticals, Inc. | Polymeric shells for medical imaging prepared from synthetic polymers, and methods for the use thereof |
US5362478A (en) * | 1993-03-26 | 1994-11-08 | Vivorx Pharmaceuticals, Inc. | Magnetic resonance imaging with fluorocarbons encapsulated in a cross-linked polymeric shell |
US5716981A (en) * | 1993-07-19 | 1998-02-10 | Angiogenesis Technologies, Inc. | Anti-angiogenic compositions and methods of use |
US5886026A (en) * | 1993-07-19 | 1999-03-23 | Angiotech Pharmaceuticals Inc. | Anti-angiogenic compositions and methods of use |
US5616608A (en) * | 1993-07-29 | 1997-04-01 | The United States Of America As Represented By The Department Of Health And Human Services | Method of treating atherosclerosis or restenosis using microtubule stabilizing agent |
US6197349B1 (en) * | 1993-08-12 | 2001-03-06 | Knoll Aktiengesellschaft | Particles with modified physicochemical properties, their preparation and uses |
US5415869A (en) * | 1993-11-12 | 1995-05-16 | The Research Foundation Of State University Of New York | Taxol formulation |
US5731334A (en) * | 1994-01-11 | 1998-03-24 | The Scripps Research Institute | Method for treating cancer using taxoid onium salt prodrugs |
US5565478A (en) * | 1994-03-14 | 1996-10-15 | The United States Of America As Represented By The Department Of Health & Human Services | Combination therapy using signal transduction inhibitors with paclitaxel and other taxane analogs |
US5670536A (en) * | 1994-04-25 | 1997-09-23 | Rhone-Poulenc Rorer S.A. | Pharmaceutical composition based on taxoids |
US5616330A (en) * | 1994-07-19 | 1997-04-01 | Hemagen/Pfc | Stable oil-in-water emulsions incorporating a taxine (taxol) and method of making same |
US5626862A (en) * | 1994-08-02 | 1997-05-06 | Massachusetts Institute Of Technology | Controlled local delivery of chemotherapeutic agents for treating solid tumors |
US5651986A (en) * | 1994-08-02 | 1997-07-29 | Massachusetts Institute Of Technology | Controlled local delivery of chemotherapeutic agents for treating solid tumors |
US6432928B1 (en) * | 1994-11-11 | 2002-08-13 | Chinoin Gyogyszer Es Vegyeszeti Termekek Gyara Rt. | Complexes and their compositions |
US6066668A (en) * | 1994-11-14 | 2000-05-23 | Bionumerik Pharmaceuticals, Inc. | Formulations and methods of reducing toxicity of antineoplastic agents |
US6179817B1 (en) * | 1995-02-22 | 2001-01-30 | Boston Scientific Corporation | Hybrid coating for medical devices |
US5681846A (en) * | 1995-03-17 | 1997-10-28 | Board Of Regents, The University Of Texas System | Extended stability formulations for paclitaxel |
US6565842B1 (en) * | 1995-06-07 | 2003-05-20 | American Bioscience, Inc. | Crosslinkable polypeptide compositions |
US6107332A (en) * | 1995-09-12 | 2000-08-22 | The Liposome Company, Inc. | Hydrolysis-promoting hydrophobic taxane derivatives |
US6051600A (en) * | 1995-09-12 | 2000-04-18 | Mayhew; Eric | Liposomal hydrolysis-promoting hydrophobic taxane derivatives |
US6610735B2 (en) * | 1995-10-26 | 2003-08-26 | Baker Norton Pharmaceuticals, Inc. | Method, compositions and kits for increasing the oral bioavailability of pharmaceutical agents |
US6441025B2 (en) * | 1996-03-12 | 2002-08-27 | Pg-Txl Company, L.P. | Water soluble paclitaxel derivatives |
US5795909A (en) * | 1996-05-22 | 1998-08-18 | Neuromedica, Inc. | DHA-pharmaceutical agent conjugates of taxanes |
US6759431B2 (en) * | 1996-05-24 | 2004-07-06 | Angiotech Pharmaceuticals, Inc. | Compositions and methods for treating or preventing diseases of body passageways |
US20070087022A1 (en) * | 1996-10-01 | 2007-04-19 | Abraxis Bioscience, Inc. | Novel formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof |
US5756537A (en) * | 1996-11-08 | 1998-05-26 | Parkash S. Gill, M.D., Inc. | Regime for paclitaxel in Kaposi's sarcoma patients |
US6458373B1 (en) * | 1997-01-07 | 2002-10-01 | Sonus Pharmaceuticals, Inc. | Emulsion vehicle for poorly soluble drugs |
US7238369B2 (en) * | 1997-03-12 | 2007-07-03 | The Regents Of The University Of California | Cationic liposome delivery of taxanes to angiogenic blood vessels |
US6197051B1 (en) * | 1997-06-18 | 2001-03-06 | Boston Scientific Corporation | Polycarbonate-polyurethane dispersions for thromobo-resistant coatings |
US20030199425A1 (en) * | 1997-06-27 | 2003-10-23 | Desai Neil P. | Compositions and methods for treatment of hyperplasia |
US20110165256A1 (en) * | 1997-06-27 | 2011-07-07 | Desai Neil P | Compositions and methods for treatment of hyperplasia |
US20070093547A1 (en) * | 1997-06-27 | 2007-04-26 | Desai Neil P | Novel formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof |
US6743826B1 (en) * | 1997-09-18 | 2004-06-01 | Human Rt | Pharmaceutical compositions containing plasma protein |
US20050004002A1 (en) * | 2002-12-09 | 2005-01-06 | American Bioscience, Inc. | Compositions and methods of delivery of pharmacological agents |
US20070129448A1 (en) * | 2002-12-09 | 2007-06-07 | Abraxis Bioscience, Inc. | Compositions and methods of delivery of pharmacological agents |
US7820788B2 (en) * | 2002-12-09 | 2010-10-26 | Abraxis Bioscience, Llc | Compositions and methods of delivery of pharmacological agents |
US7923536B2 (en) * | 2002-12-09 | 2011-04-12 | Abraxis Bioscience, Llc | Compositions and methods of delivery of pharmacological agents |
US20070117133A1 (en) * | 2004-05-14 | 2007-05-24 | Abraxis Bioscience, Inc. | Sparc and methods of use thereof |
US20070166388A1 (en) * | 2005-02-18 | 2007-07-19 | Desai Neil P | Combinations and modes of administration of therapeutic agents and combination therapy |
US7758891B2 (en) * | 2005-02-18 | 2010-07-20 | Abraxis Bioscience, Llc | Combinations and modes of administration of therapeutic agents and combination therapy |
US20070116774A1 (en) * | 2005-02-18 | 2007-05-24 | Abraxis Bioscience, Inc. | Methods and compositions for treating proliferative diseases |
US7332568B2 (en) * | 2005-02-18 | 2008-02-19 | Abraxis Bioscience, Inc. | Q3 SPARC deletion mutant and uses thereof |
US7780984B2 (en) * | 2005-02-18 | 2010-08-24 | Abraxis Bioscience, Llc | Methods and compositions for treating proliferative diseases |
US20080063724A1 (en) * | 2005-02-18 | 2008-03-13 | Desai Neil P | Methods and compostions for treating proliferative diseases |
US7771751B2 (en) * | 2005-08-31 | 2010-08-10 | Abraxis Bioscience, Llc | Compositions comprising poorly water soluble pharmaceutical agents and antimicrobial agents |
US20070117744A1 (en) * | 2005-08-31 | 2007-05-24 | Desai Neil P | Compositions comprising poorly water soluble pharmaceutical agents and antimicrobial agents |
US20110118342A1 (en) * | 2005-08-31 | 2011-05-19 | Tapas De | Compositions and methods for preparation of poorly water soluble drugs with increased stability |
US20110151012A1 (en) * | 2005-08-31 | 2011-06-23 | Desai Neil P | Compositions comprising poorly water soluble pharmaceutical agents and antimicrobial agents |
US20070082838A1 (en) * | 2005-08-31 | 2007-04-12 | Abraxis Bioscience, Inc. | Compositions and methods for preparation of poorly water soluble drugs with increased stability |
US7981445B2 (en) * | 2005-08-31 | 2011-07-19 | Abraxis Bioscience, Llc | Compositions and methods for preparation of poorly water soluble drugs with increased stability |
US20110196026A1 (en) * | 2005-08-31 | 2011-08-11 | Abraxis Bioscience, Inc. | Compositions and methods for preparation of poorly water soluble drugs with increased stability |
US20100112077A1 (en) * | 2006-11-06 | 2010-05-06 | Abraxis Bioscience, Llc | Nanoparticles of paclitaxel and albumin in combination with bevacizumab against cancer |
US20100048499A1 (en) * | 2006-12-14 | 2010-02-25 | Desai Neil P | Breast cancer therapy based on hormone receptor status with nanoparticles comprising taxane |
US20100183728A1 (en) * | 2007-03-07 | 2010-07-22 | Desai Neil P | Nanoparticle comprising rapamycin and albumin as anticancer agent |
US20100166869A1 (en) * | 2007-05-03 | 2010-07-01 | Desai Neil P | Methods and compositions for treating pulmonary hypertension |
US20100215751A1 (en) * | 2007-06-01 | 2010-08-26 | Desai Neil P | Methods and compositions for treating recurrent cancer |
US20090263483A1 (en) * | 2008-04-10 | 2009-10-22 | Desai Neil P | Nanoparticle formulations and uses thereof |
Non-Patent Citations (4)
Title |
---|
Fan et al. "Formulation Optimization of Paclitaxel Carried by Paginated Emulsions based on Artificial Neural Network," in Pharmaceutical Research, Vol. 21, No. 9, September 2004 discloses injectable paclitaxel carried by Paginated emulsions. * |
Felix Kratz, "Albumin as a drug carrier: Design of prodrugs, drug conjugates and nanoparticles," in Journal of controlled Release, 132, (2008), 171-183. * |
Gradishar et al. ("Phase III Trial of Nanoparticle Albumin-Bound Paclitaxel compared with polyethylated Castor Oil-Based Paclitaxel in Women With Breast Cancer," in Journal of clinical oncology, vol. 23, no. 31, November 1 2005). * |
Suri et al. (Nanotechnology-based drug delivery systems," in Journal of Occupational Medicine and Toxicology, Dec. 2007). * |
Cited By (54)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070087022A1 (en) * | 1996-10-01 | 2007-04-19 | Abraxis Bioscience, Inc. | Novel formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof |
US8137684B2 (en) | 1996-10-01 | 2012-03-20 | Abraxis Bioscience, Llc | Formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof |
US20110165256A1 (en) * | 1997-06-27 | 2011-07-07 | Desai Neil P | Compositions and methods for treatment of hyperplasia |
US20070093547A1 (en) * | 1997-06-27 | 2007-04-26 | Desai Neil P | Novel formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof |
US20030199425A1 (en) * | 1997-06-27 | 2003-10-23 | Desai Neil P. | Compositions and methods for treatment of hyperplasia |
US8853260B2 (en) | 1997-06-27 | 2014-10-07 | Abraxis Bioscience, Llc | Formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof |
US8314156B2 (en) | 2002-12-09 | 2012-11-20 | Abraxis Bioscience, Llc | Compositions and methods of delivery of pharmacological agents |
US8138229B2 (en) | 2002-12-09 | 2012-03-20 | Abraxis Bioscience, Llc | Compositions and methods of delivery of pharmacological agents |
US9012519B2 (en) | 2002-12-09 | 2015-04-21 | Abraxis Bioscience, Llc | Compositions and methods of delivery of pharmacological agents |
US9012518B2 (en) | 2002-12-09 | 2015-04-21 | Abraxis Bioscience, Llc | Compositions and methods of delivery of pharmacological agents |
US8846771B2 (en) | 2002-12-09 | 2014-09-30 | Abraxis Bioscience, Llc | Compositions and methods of delivery of pharmacological agents |
US20090304805A1 (en) * | 2005-02-18 | 2009-12-10 | Desai Neil P | Combinations and modes of administration of therapeutic agents and combination therapy |
US8034375B2 (en) | 2005-02-18 | 2011-10-11 | Abraxis Bioscience, Llc | Combinations and modes of administration of therapeutic agents and combination therapy |
US9101543B2 (en) | 2005-02-18 | 2015-08-11 | Abraxis Bioscience, Llc | Combinations and modes of administration of therapeutic agents and combination therapy |
US8735394B2 (en) | 2005-02-18 | 2014-05-27 | Abraxis Bioscience, Llc | Combinations and modes of administration of therapeutic agents and combination therapy |
US8268348B2 (en) | 2005-02-18 | 2012-09-18 | Abraxis Bioscience, Llc | Combinations and modes of administration of therapeutic agents and combination therapy |
US9561288B2 (en) | 2005-02-18 | 2017-02-07 | Abraxis Bioscience, Llc | Combinations and modes of administration of therapeutic agents and combination therapy |
US9308180B2 (en) | 2005-08-31 | 2016-04-12 | Abraxis Bioscience, Llc | Compositions and methods for preparation of poorly water soluble drugs with increased stability |
US20110118342A1 (en) * | 2005-08-31 | 2011-05-19 | Tapas De | Compositions and methods for preparation of poorly water soluble drugs with increased stability |
US9675578B2 (en) | 2006-12-14 | 2017-06-13 | Abraxis Bioscience, Llc | Breast cancer therapy based on hormone receptor status with nanoparticles comprising taxane |
US20100048499A1 (en) * | 2006-12-14 | 2010-02-25 | Desai Neil P | Breast cancer therapy based on hormone receptor status with nanoparticles comprising taxane |
US8999396B2 (en) | 2006-12-14 | 2015-04-07 | Abraxis Bioscience, Llc | Breast cancer therapy based on hormone receptor status with nanoparticles comprising taxane |
US9724323B2 (en) | 2006-12-14 | 2017-08-08 | Abraxis Bioscience, Llc | Breast cancer therapy based on hormone receptor status with nanoparticles comprising taxane |
US10682420B2 (en) | 2006-12-14 | 2020-06-16 | Abraxis Bioscience, Llc | Breast cancer therapy based on hormone receptor status with nanoparticles comprising taxane |
US20100183728A1 (en) * | 2007-03-07 | 2010-07-22 | Desai Neil P | Nanoparticle comprising rapamycin and albumin as anticancer agent |
US8911786B2 (en) | 2007-03-07 | 2014-12-16 | Abraxis Bioscience, Llc | Nanoparticle comprising rapamycin and albumin as anticancer agent |
US20100166869A1 (en) * | 2007-05-03 | 2010-07-01 | Desai Neil P | Methods and compositions for treating pulmonary hypertension |
US20100215751A1 (en) * | 2007-06-01 | 2010-08-26 | Desai Neil P | Methods and compositions for treating recurrent cancer |
US8927019B2 (en) | 2007-06-01 | 2015-01-06 | Abraxis Bioscience, Llc | Methods and compositions for treating recurrent cancer |
US20090263483A1 (en) * | 2008-04-10 | 2009-10-22 | Desai Neil P | Nanoparticle formulations and uses thereof |
US10206887B2 (en) | 2009-04-15 | 2019-02-19 | Abraxis Bioscience, Llc | Prion free nanoparticle compositions and methods of making thereof |
US9446003B2 (en) | 2009-04-15 | 2016-09-20 | Abraxis Bioscience, Llc | Prion free nanoparticle compositions and methods of making thereof |
US20110052706A1 (en) * | 2009-08-28 | 2011-03-03 | Nordmark Arzeimittel GmbH & Co. KG | Pancreatine pellets and method of producing same |
US9370494B2 (en) | 2010-03-26 | 2016-06-21 | Abraxis Bioscience, Llc | Methods for treating hepatocellular carcinoma |
US10660965B2 (en) | 2010-03-29 | 2020-05-26 | Abraxis Bioscience, Llc | Methods of enhancing drug delivery and effectiveness of therapeutic agents |
US9597409B2 (en) | 2010-03-29 | 2017-03-21 | Abraxis Bioscience, Llc | Methods of treating cancer |
US9393318B2 (en) | 2010-03-29 | 2016-07-19 | Abraxis Bioscience, Llc | Methods of treating cancer |
US9399071B2 (en) | 2010-06-04 | 2016-07-26 | Abraxis Bioscience, Llc | Methods of treatment of pancreatic cancer |
US9399072B2 (en) | 2010-06-04 | 2016-07-26 | Abraxis Bioscience, Llc | Methods of treatment of pancreatic cancer |
US9820949B2 (en) | 2010-06-04 | 2017-11-21 | Abraxis Bioscience, Llc | Methods of treatment of pancreatic cancer |
US9585960B2 (en) | 2011-12-14 | 2017-03-07 | Abraxis Bioscience, Llc | Use of polymeric excipients for lyophilization or freezing of particles |
US10076501B2 (en) | 2011-12-14 | 2018-09-18 | Abraxis Bioscience, Llc | Use of polymeric excipients for lyophilization or freezing of particles |
US10555912B2 (en) | 2011-12-14 | 2020-02-11 | Abraxis Bioscience, Llc | Use of polymeric excipients for lyophilization or freezing of particles |
US9149455B2 (en) | 2012-11-09 | 2015-10-06 | Abraxis Bioscience, Llc | Methods of treating melanoma |
US10744110B2 (en) | 2013-03-12 | 2020-08-18 | Abraxis Bioscience, Llc | Methods of treating lung cancer |
US9962373B2 (en) | 2013-03-14 | 2018-05-08 | Abraxis Bioscience, Llc | Methods of treating bladder cancer |
US10413531B2 (en) | 2013-03-14 | 2019-09-17 | Abraxis Bioscience, Llc | Methods of treating bladder cancer |
US10527604B1 (en) | 2015-03-05 | 2020-01-07 | Abraxis Bioscience, Llc | Methods of assessing suitability of use of pharmaceutical compositions of albumin and paclitaxel |
US10705070B1 (en) | 2015-03-05 | 2020-07-07 | Abraxis Bioscience, Llc | Methods of assessing suitability of use of pharmaceutical compositions of albumin and poorly water soluble drug |
US10900951B1 (en) | 2015-03-05 | 2021-01-26 | Abraxis Bioscience, Llc | Methods of assessing suitability of use of pharmaceutical compositions of albumin and paclitaxel |
US11320416B1 (en) | 2015-03-05 | 2022-05-03 | Abraxis Bioscience, Llc | Methods of assessing suitability of use of pharmaceutical compositions of albumin and poorly water soluble drug |
US10973806B2 (en) | 2015-06-29 | 2021-04-13 | Abraxis Bioscience, Llc | Methods of treating epithelioid cell tumors comprising administering a composition comprising nanoparticles comprising an mTOR inhibitor and an albumin |
US11944708B2 (en) | 2018-03-20 | 2024-04-02 | Abraxis Bioscience, Llc | Methods of treating central nervous system disorders via administration of nanoparticles of an mTOR inhibitor and an albumin |
US11497737B2 (en) | 2019-10-28 | 2022-11-15 | Abraxis Bioscience, Llc | Pharmaceutical compositions of albumin and rapamycin |
Also Published As
Publication number | Publication date |
---|---|
US5439686A (en) | 1995-08-08 |
US5560933A (en) | 1996-10-01 |
CN1839806B (en) | 2011-04-13 |
CN1839806A (en) | 2006-10-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20110052708A1 (en) | Methods and formulations for the delivery of pharmacologically active agents | |
US20090048331A1 (en) | Methods and formulations for the delivery of pharmacologically active agents | |
US20060073175A1 (en) | Methods and formulations for delivery of pharmacologically active agents | |
Tian et al. | Co-delivery of paclitaxel and cisplatin with biocompatible PLGA–PEG nanoparticles enhances chemoradiotherapy in non-small cell lung cancer models | |
Gelperina et al. | Toxicological studies of doxorubicin bound to polysorbate 80-coated poly (butyl cyanoacrylate) nanoparticles in healthy rats and rats with intracranial glioblastoma | |
US20150342872A1 (en) | Use of Paclitaxel Particles | |
Strickley | Solubilizing excipients in oral and injectable formulations | |
Brigger et al. | Negative preclinical results with stealth® nanospheres-encapsulated doxorubicin in an orthotopic murine brain tumor model | |
Seo et al. | Self-assembled 20-nm 64Cu-micelles enhance accumulation in rat glioblastoma | |
US11166913B2 (en) | Tumor therapeutic agent and kit containing gemcitabine liposome composition | |
JP5419716B2 (en) | Antitumor effect potentiator comprising oxaliplatin liposome preparation and antitumor agent containing the liposome preparation | |
US20080293796A1 (en) | Parenteral and oral formulations of benzimidazoles | |
Siegal | Which drug or drug delivery system can change clinical practice for brain tumor therapy? | |
Ismail et al. | Targeted liposomes for combined delivery of artesunate and temozolomide to resistant glioblastoma | |
US9259390B2 (en) | Parenteral and oral formulations of benzimidazoles | |
CN102579337B (en) | Long circulation lipid nano-suspension containing docetaxel and preparation method thereof | |
Zhang et al. | Pharmacokinetics, distribution and anti-tumor efficacy of liposomal mitoxantrone modified with a luteinizing hormone-releasing hormone receptor-specific peptide | |
EP2310009B1 (en) | Parenteral and oral formulations of benzimidazoles | |
EP2421506A2 (en) | Nanocarrier therapy for treating invasive tumors | |
US11806330B2 (en) | PACA and cabazitaxel for anti-cancer treatment | |
US20230172856A1 (en) | Liposome formulations for treatment of cancers and drug resistance of cancers | |
US20220257525A1 (en) | Drug delivery system for treatment of cancer | |
WO2022124898A1 (en) | Auristatin-loaded liposomes and uses thereof. | |
Hong et al. | Therapy of central nervous system leukemia in mice by liposome-entrapped 1-β-D-arabinofuranosylcytosine | |
Oborotova et al. | Role of new pharmaceutical technologies in enhancing the selectivity of antitumor drugs |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: ABRAXIS BIOSCIENCE, LLC, CALIFORNIA Free format text: MERGER;ASSIGNOR:ABRAXIS BIOSCIENCE, INC.;REEL/FRAME:025016/0255 Effective date: 20071113 Owner name: ABRAXIS BIOSCIENCE, INC., CALIFORNIA Free format text: MERGER;ASSIGNOR:AMERICAN BIOSCIENCE, INC.;REEL/FRAME:025016/0248 Effective date: 20060418 Owner name: AMERICAN BIOSCIENCE, INC., CALIFORNIA Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:SOON-SHIONG, PATRICK;DESAI, NEIL P.;SIGNING DATES FROM 20020612 TO 20020702;REEL/FRAME:025016/0240 |
|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |