WO1996005821A1 - Liposomal verkapseltes taxol, seine herstellung und seine verwendung - Google Patents
Liposomal verkapseltes taxol, seine herstellung und seine verwendung Download PDFInfo
- Publication number
- WO1996005821A1 WO1996005821A1 PCT/DE1995/001163 DE9501163W WO9605821A1 WO 1996005821 A1 WO1996005821 A1 WO 1996005821A1 DE 9501163 W DE9501163 W DE 9501163W WO 9605821 A1 WO9605821 A1 WO 9605821A1
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- WIPO (PCT)
- Prior art keywords
- liposomally encapsulated
- taxol
- anspmch
- encapsulated taxol
- taxol according
- Prior art date
Links
- 229930012538 Paclitaxel Natural products 0.000 title claims abstract description 72
- 229960001592 paclitaxel Drugs 0.000 title claims abstract description 72
- 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 title claims abstract description 72
- 238000002360 preparation method Methods 0.000 title description 18
- 238000000265 homogenisation Methods 0.000 claims abstract description 10
- 239000000443 aerosol Substances 0.000 claims abstract description 7
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 7
- 206010027458 Metastases to lung Diseases 0.000 claims abstract description 5
- 239000002502 liposome Substances 0.000 claims description 29
- 150000002632 lipids Chemical class 0.000 claims description 25
- 238000004519 manufacturing process Methods 0.000 claims description 9
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- 239000006185 dispersion Substances 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 6
- 150000001450 anions Chemical class 0.000 claims description 6
- 229960004562 carboplatin Drugs 0.000 claims description 6
- 190000008236 carboplatin Chemical compound 0.000 claims description 6
- 239000003380 propellant Substances 0.000 claims description 6
- 239000008393 encapsulating agent Substances 0.000 claims description 5
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- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- OGQYPPBGSLZBEG-UHFFFAOYSA-N dimethyl(dioctadecyl)azanium Chemical compound CCCCCCCCCCCCCCCCCC[N+](C)(C)CCCCCCCCCCCCCCCCCC OGQYPPBGSLZBEG-UHFFFAOYSA-N 0.000 claims description 4
- 238000001704 evaporation Methods 0.000 claims description 4
- 230000008020 evaporation Effects 0.000 claims description 4
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 claims description 4
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims description 4
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 claims description 3
- 201000009030 Carcinoma Diseases 0.000 claims description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 3
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 claims description 3
- 229910019142 PO4 Inorganic materials 0.000 claims description 3
- 239000000824 cytostatic agent Substances 0.000 claims description 3
- 230000001085 cytostatic effect Effects 0.000 claims description 3
- 239000012528 membrane Substances 0.000 claims description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 3
- 239000010452 phosphate Substances 0.000 claims description 3
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- KILNVBDSWZSGLL-KXQOOQHDSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC KILNVBDSWZSGLL-KXQOOQHDSA-N 0.000 claims description 2
- PORPENFLTBBHSG-MGBGTMOVSA-N 1,2-dihexadecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCC PORPENFLTBBHSG-MGBGTMOVSA-N 0.000 claims description 2
- 206010027457 Metastases to liver Diseases 0.000 claims description 2
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- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- ATBOMIWRCZXYSZ-XZBBILGWSA-N [1-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-3-hexadecanoyloxypropan-2-yl] (9e,12e)-octadeca-9,12-dienoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC ATBOMIWRCZXYSZ-XZBBILGWSA-N 0.000 claims description 2
- 239000000654 additive Substances 0.000 claims description 2
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 claims description 2
- 239000003995 emulsifying agent Substances 0.000 claims description 2
- 201000001441 melanoma Diseases 0.000 claims description 2
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 claims description 2
- 239000002105 nanoparticle Substances 0.000 claims description 2
- 230000007935 neutral effect Effects 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 239000011148 porous material Substances 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- 150000003408 sphingolipids Chemical class 0.000 claims description 2
- 239000008117 stearic acid Substances 0.000 claims description 2
- -1 sulfatide Chemical class 0.000 claims description 2
- 238000000034 method Methods 0.000 claims 3
- 208000003174 Brain Neoplasms Diseases 0.000 claims 1
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 claims 1
- 239000008346 aqueous phase Substances 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 238000012412 chemical coupling Methods 0.000 claims 1
- 150000002170 ethers Chemical class 0.000 claims 1
- 238000001125 extrusion Methods 0.000 claims 1
- 235000021317 phosphate Nutrition 0.000 claims 1
- 150000008104 phosphatidylethanolamines Chemical class 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 claims 1
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- 206010028980 Neoplasm Diseases 0.000 abstract description 8
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- 230000001225 therapeutic effect Effects 0.000 abstract description 5
- 239000003814 drug Substances 0.000 abstract description 3
- DVQHYTBCTGYNNN-UHFFFAOYSA-N azane;cyclobutane-1,1-dicarboxylic acid;platinum Chemical compound N.N.[Pt].OC(=O)C1(C(O)=O)CCC1 DVQHYTBCTGYNNN-UHFFFAOYSA-N 0.000 abstract 1
- 230000009471 action Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
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- 239000008389 polyethoxylated castor oil Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
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- NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 2
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- 230000000118 anti-neoplastic effect Effects 0.000 description 1
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- 239000001273 butane Substances 0.000 description 1
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- 238000010790 dilution Methods 0.000 description 1
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- 239000000539 dimer Substances 0.000 description 1
- ZGSPNIOCEDOHGS-UHFFFAOYSA-L disodium [3-[2,3-di(octadeca-9,12-dienoyloxy)propoxy-oxidophosphoryl]oxy-2-hydroxypropyl] 2,3-di(octadeca-9,12-dienoyloxy)propyl phosphate Chemical compound [Na+].[Na+].CCCCCC=CCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COP([O-])(=O)OCC(O)COP([O-])(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COC(=O)CCCCCCCC=CCC=CCCCCC ZGSPNIOCEDOHGS-UHFFFAOYSA-L 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
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- 230000016507 interphase Effects 0.000 description 1
- 239000001282 iso-butane Substances 0.000 description 1
- 238000004898 kneading Methods 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000017066 negative regulation of growth Effects 0.000 description 1
- 208000004235 neutropenia Diseases 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008521 reorganization Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000002456 taxol group Chemical group 0.000 description 1
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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
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
- A61K9/1277—Processes for preparing; Proliposomes
Definitions
- the invention relates to liposomally encapsulated taxol. its manufacture and its use. Areas of application of the invention are medicine and the pharmaceutical industry.
- Taxol is a natural substance found in the bark of various yew species (Taxazeen), which is derived from these barks [J. Amer. Chem. Soc, 93: 2325 (1971)] or more recently also by chemical synthesis [J. Amer. Chem. Soc, 1110: 5917-5919 (1988)]. Taxol has a completely new mode of action compared to previously known cytostatics [Ann. NY. Acad. Be. 466: 733-744 (1986); Sartorelli, A. (ed.): Molecular Actions and Targets for Cancer Chemotherapeutic Agents. Academic Press, New York, 1981, pp. 483-507].
- Taxol shows a clear antineoplastic activity against various tumors, e.g. against implanted B16 melanoma, P388 leukemia and against human breast tumors.
- Taxol is severely limited due to its low water solubility.
- Solubilizers such as Cremophor (polyethoxylated castor oil) and alcohol improve the solubility, but lead to the use
- Taxol as an almost water-insoluble substance can be dissolved with high efficiency in the lipid phase of liposomes of a suitable composition, so that the toxicities observed by Cremophor EL in humans, including increased chylomicron formation, should no longer occur.
- the therapeutic effectiveness of free, liposomally encapsulated and nanoparticulate taxol is compared in vitro on two leukaemias, the P388 and the L1210. While the inhibition of growth of the P388 cells was the same for all 3 drug forms, the L1210 was more sensitive to the nanoparticulate form.
- Taxol liposomes produced show improved stability.
- Taxol-liposome combinations are claimed, of which in particular
- Vesicles with a positive charge based on cardiolipin, phosphate idylcholine and cholesterol were produced and examined.
- the aim of the invention is to provide liposomally encapsulated taxol with a high taxol content and higher stability, and thus increased therapeutic effectiveness.
- the task is to develop specific forms of Taxol encapsulation and to use them, possibly in combination with other free or liposomally encapsulated substances, for the treatment of different types of tumors and localizations.
- the focus is also on preventing the dose-limiting neutropenic effect of the unencapsulated taxol, e.g. by combination with liposomal carboplatin.
- the invention also relates to a pharmaceutical preparation which contains the liposomally encapsulated taxol according to the invention and pharmaceutically customary excipients and additives.
- a practically advantageously usable mixture contains 0.98 mg taxol in 50 mg phosphatidylcholine (98% of the amount of taxol used).
- the liposomal encapsulation takes place by high pressure homogenization or by spontaneous vesicle formation.
- a prefabricated liposome mixture in solid or liquid form is combined with taxol, subsequently homogenized several times (preferably twice) at 5-160 MPa and optionally subsequently lyophilized.
- the production process for the production of a taxol-containing liposomal preparation by means of high-pressure homogenization, and possibly the release of liposomes from such a preparation comprises the following steps:
- REPLACEMENT LEAF Liposomes according to Example 1 were used for animal experiments. It could be shown, inter alia, on a human mamma carcinoma (MaTu) that this liposome preparation compared to free taxol (4 days of therapy, 12.5 mg / kg per day) after only one application of 50 mg / kg showed improved therapeutic efficacy with lower haematotoxicity (Fig. 1 + 2).
- the encapsulants used are a) a natural, semi-synthetic or fully synthetic amphiphile, such as a lipid, a surfactant or an emulsifier, b) a charged lipid component and / or a saturated lipid component, an ether lipid component, c) a polymer d) a carrier liquid and optionally additional auxiliaries, such as Contains nano particles.
- the amphiphile preferably has the formula I given in claim 3.
- the charged lipid component used is preferably: the anion of dicethylphosphate, palmitic acid, stearic acid, the anion of a phospholipid, such as phosphatidylserine or phosphatidic acid, or the anion of a sphingolipid such as sulfatide.
- phosphatidylglycerol is used as the charged lipid component.
- the invention can equally be implemented with neutral lipid components such as phosphatidylcholine or saturated lipid components such as dipalmitoylphosphatidylcholine.
- the polymer used is e.g. Polyethylene glycol of molecular weight 2000-10000.
- Physiological saline is generally used as the carrier liquid.
- aqueous medium in volume fractions of 1 to 30% of the volume of the preparation and mechanical mixing e.g. the three-dimensional gel structure is disassembled and the preformed liposomes released by manual shaking or using a vortex mixer.
- the liposome dispersion can be filtered through filters with a pore size of 0.1 ⁇ m to 1 ⁇ m.
- the preparation according to the invention which contains liposomes in a tight package (liposome gel), is suitable as an active substance depot which slowly releases the active substance, either in dissolved form or in the form of individual liposomes containing active substance.
- This preparation can be applied by injection (e.g. i.m., i.p.) or implantation. However, insertion into body cavities or application to mucous membranes, the cornea of the eye (cornea) or areas of the skin is also possible.
- the preparation thus serves as a carrier of the active ingredient and, if necessary, for its modified release.
- the preparation according to the invention which contains liposomes in free-flowing form, is suitable as a carrier of the active ingredient.
- This preparation can be applied by injection (e.g. i.v., i.m.) or also by introducing it into body cavities or by applying it to mucous membranes, the cornea of the eye (comea) or areas of skin.
- the encapsulated liposomes according to the invention lead to a distribution of the liposomal active ingredient in the body, which selectively brings about a high and long-lasting active ingredient concentration at the site of action and thus to an improvement in the action or an improvement in the ratio of action to side effect.
- the taxol / encapsulant / propellant mixture of metered dose aerosols is sprayed and forms after the evaporation of
- preformed taxol liposomes can be nebulized. This route is particularly preferable if direct use against lung metastases is intended.
- the liposomally encapsulated taxol can be used as a cytostatic. This can be used alone or in combination with other active ingredients such as carboplatin or liposomally encapsulated carboplatin. Preference is given to use against him tumors, malignant melanomas, liver metastases, pulmonary metastases, breast carcinomas and against urogenital carcinomas. During treatment i.a. A human breast carcinoma on the nude mouse showed a significant tumor volume inhibition after a single administration of 50 mg kg liposomally encapsulated taxol compared to the treated taxol group (4x12.5 mg / kg).
- a lipid film consisting of 1500 mg of egg phosphatidylcholine and 30 mg of taxol is dispersed in 30 ml of sterile, calcium-free phosphate-buffered (pH 7.2-7.4) sodium chloride solution.
- the resulting dispersion of multilayer liposomes is treated in a high pressure homogenizer (Gaulin Mikrolab 40) at 700 bar.
- the resulting liposome dispersion (SUV) can be stored for a short time at 4 degrees Celsius and is suitable for parenteral (IV) application. Gel formation or lyophilization is suitable for longer storage.
- Liposomes produced as in Example 1 are aerosolized with a suitable nebulizer (e.g. Aero-Tech II) and thus made accessible for inhalation.
- a suitable nebulizer e.g. Aero-Tech II
- 200 mg taxol, 200 mg encapsulant according to claim 2 and 400 ul ethanol (90%) are metered into a pressurized gas container.
- a metering valve e.g. Perfect Valois DF 10/150 ACT
- 10 ml of liquefied dimethyl ether are added to the preparation, so that the clear to opalescent or slightly cloudy solution is formed.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Dispersion Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Otolaryngology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Epoxy Compounds (AREA)
- Fats And Perfumes (AREA)
Abstract
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DK95929002T DK0776202T3 (da) | 1994-08-20 | 1995-08-18 | Liposomalt indkapslet taxol, dets fremstilling af dets anvendelse |
DE59508360T DE59508360D1 (de) | 1994-08-20 | 1995-08-18 | Liposomal verkapseltes taxol, seine herstellung und seine verwendung |
US08/793,238 US6090955A (en) | 1994-08-20 | 1995-08-18 | Liposome-encapsulated taxol, its preparation and its use |
EP95929002A EP0776202B1 (de) | 1994-08-20 | 1995-08-18 | Liposomal verkapseltes taxol, seine herstellung und seine verwendung |
AT95929002T ATE192924T1 (de) | 1994-08-20 | 1995-08-18 | Liposomal verkapseltes taxol, seine herstellung und seine verwendung |
GR20000401857T GR3034162T3 (en) | 1994-08-20 | 2000-08-09 | Liposome-encapsulated taxol, its preparation and its use |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DEP4430593.1 | 1994-08-20 | ||
DE4430593A DE4430593C2 (de) | 1994-08-20 | 1994-08-20 | Verfahren zur Herstellung von Liposomal verkapseltem Taxol |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1996005821A1 true WO1996005821A1 (de) | 1996-02-29 |
Family
ID=6526804
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/DE1995/001163 WO1996005821A1 (de) | 1994-08-20 | 1995-08-18 | Liposomal verkapseltes taxol, seine herstellung und seine verwendung |
Country Status (7)
Country | Link |
---|---|
US (1) | US6090955A (de) |
EP (1) | EP0776202B1 (de) |
AT (1) | ATE192924T1 (de) |
DE (3) | DE4447770C2 (de) |
DK (1) | DK0776202T3 (de) |
GR (1) | GR3034162T3 (de) |
WO (1) | WO1996005821A1 (de) |
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EP1011638A1 (de) * | 1997-09-23 | 2000-06-28 | Research Development Foundation | Aerosole, enthaltend kleine liposomenpartikel, zur verabreichung von antikrebsmitteln |
JP2001524990A (ja) * | 1998-07-01 | 2001-12-04 | ネオファーム、インコーポレイティッド | リポソームに封入されたタキサンの投与方法 |
KR100450317B1 (ko) * | 1999-08-27 | 2004-09-30 | 르 라보레또레 쎄르비에르 | 피리딘 화합물, 이들을 제조하는 방법 및 이들을 함유하는약제 조성물 |
US7348025B2 (en) | 1997-09-23 | 2008-03-25 | Research Development Foundation | Small particle liposome aerosols for delivery of anticancer drugs |
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WO1993018751A1 (en) * | 1992-03-23 | 1993-09-30 | Georgetown University | Liposome encapsulated taxol and a method of using the same |
WO1993025225A1 (en) * | 1992-06-17 | 1993-12-23 | University Of Massachusetts Medical Center | Liposomal formulations for administering to cancer patients |
WO1994026254A1 (en) * | 1993-05-17 | 1994-11-24 | The Liposome Company, Inc. | Incorporation of taxol into liposomes and gels |
US5415869A (en) * | 1993-11-12 | 1995-05-16 | The Research Foundation Of State University Of New York | Taxol formulation |
-
1994
- 1994-08-20 DE DE4447770A patent/DE4447770C2/de not_active Expired - Lifetime
- 1994-08-20 DE DE4430593A patent/DE4430593C2/de not_active Expired - Lifetime
-
1995
- 1995-08-18 WO PCT/DE1995/001163 patent/WO1996005821A1/de not_active Application Discontinuation
- 1995-08-18 DK DK95929002T patent/DK0776202T3/da active
- 1995-08-18 DE DE59508360T patent/DE59508360D1/de not_active Revoked
- 1995-08-18 EP EP95929002A patent/EP0776202B1/de not_active Revoked
- 1995-08-18 AT AT95929002T patent/ATE192924T1/de not_active IP Right Cessation
- 1995-08-18 US US08/793,238 patent/US6090955A/en not_active Expired - Lifetime
-
2000
- 2000-08-09 GR GR20000401857T patent/GR3034162T3/el not_active IP Right Cessation
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WO1993018751A1 (en) * | 1992-03-23 | 1993-09-30 | Georgetown University | Liposome encapsulated taxol and a method of using the same |
WO1993025225A1 (en) * | 1992-06-17 | 1993-12-23 | University Of Massachusetts Medical Center | Liposomal formulations for administering to cancer patients |
WO1994026254A1 (en) * | 1993-05-17 | 1994-11-24 | The Liposome Company, Inc. | Incorporation of taxol into liposomes and gels |
US5415869A (en) * | 1993-11-12 | 1995-05-16 | The Research Foundation Of State University Of New York | Taxol formulation |
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Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1011638A1 (de) * | 1997-09-23 | 2000-06-28 | Research Development Foundation | Aerosole, enthaltend kleine liposomenpartikel, zur verabreichung von antikrebsmitteln |
EP1011638A4 (de) * | 1997-09-23 | 2006-06-28 | Res Dev Foundation | Aerosole, enthaltend kleine liposomenpartikel, zur verabreichung von antikrebsmitteln |
US7341739B2 (en) | 1997-09-23 | 2008-03-11 | Research Development Foundation | Small particle liposome aerosols for delivery of anti-cancer drugs |
US7348025B2 (en) | 1997-09-23 | 2008-03-25 | Research Development Foundation | Small particle liposome aerosols for delivery of anticancer drugs |
JP2001524990A (ja) * | 1998-07-01 | 2001-12-04 | ネオファーム、インコーポレイティッド | リポソームに封入されたタキサンの投与方法 |
JP2004059590A (ja) * | 1998-07-01 | 2004-02-26 | Neopharm Inc | リポソームに封入されたタキサンの投与方法 |
KR100450317B1 (ko) * | 1999-08-27 | 2004-09-30 | 르 라보레또레 쎄르비에르 | 피리딘 화합물, 이들을 제조하는 방법 및 이들을 함유하는약제 조성물 |
CN112656764A (zh) * | 2020-12-28 | 2021-04-16 | 吉林大学 | 一种紫杉醇铂类共载靶向长循环脂质体及应用 |
Also Published As
Publication number | Publication date |
---|---|
ATE192924T1 (de) | 2000-06-15 |
DE4447770C2 (de) | 2002-12-19 |
DE59508360D1 (de) | 2000-06-21 |
GR3034162T3 (en) | 2000-11-30 |
DK0776202T3 (da) | 2000-11-13 |
EP0776202B1 (de) | 2000-05-17 |
EP0776202A1 (de) | 1997-06-04 |
US6090955A (en) | 2000-07-18 |
DE4430593C2 (de) | 1999-01-14 |
DE4430593A1 (de) | 1996-02-22 |
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