JP2609183B2 - リポソーム製剤 - Google Patents

リポソーム製剤

Info

Publication number: JP2609183B2
Authority: JP; Japan
Prior art keywords: liposome; drug; cholesterol; neutral; dispersion
Prior art date: 1990-07-16
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.): Expired - Fee Related

Application number

JP3199794A

Other languages

English (en)

Japanese (ja)

Other versions

JPH05194191A (ja

Inventor

寛菊地

清人谷内

貞雄広田

Original Assignee

第一製薬株式会社

Priority date (The priority date 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 date listed.)

1990-07-16

Filing date

1991-07-16

Publication date

1997-05-14

1991-07-16 Application filed by 第一製薬株式会社 filed Critical 第一製薬株式会社

1991-07-16 Priority to JP3199794A priority Critical patent/JP2609183B2/ja

1993-08-03 Publication of JPH05194191A publication Critical patent/JPH05194191A/ja

1997-05-14 Application granted granted Critical

1997-05-14 Publication of JP2609183B2 publication Critical patent/JP2609183B2/ja

2012-05-14 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

239000002502 liposome Substances 0.000 title claims description 82
238000002360 preparation method Methods 0.000 title claims description 25
239000003814 drug Substances 0.000 claims abstract description 54
229940079593 drug Drugs 0.000 claims abstract description 52
239000012528 membrane Substances 0.000 claims abstract description 34
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 claims abstract description 20
-1 anionic phospholipid Chemical class 0.000 claims abstract description 15
235000012000 cholesterol Nutrition 0.000 claims abstract description 10
150000001768 cations Chemical group 0.000 claims abstract description 9
238000000034 method Methods 0.000 claims description 20
239000003125 aqueous solvent Substances 0.000 claims description 17
239000002245 particle Substances 0.000 claims description 16
230000014759 maintenance of location Effects 0.000 claims description 13
239000008280 blood Substances 0.000 claims description 11
210000004369 blood Anatomy 0.000 claims description 11
230000007935 neutral effect Effects 0.000 claims description 10
150000003904 phospholipids Chemical class 0.000 claims description 9
239000003792 electrolyte Substances 0.000 claims description 8
150000002632 lipids Chemical class 0.000 claims description 8
239000002253 acid Substances 0.000 claims description 3
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims 2
229910052698 phosphorus Inorganic materials 0.000 claims 2
239000011574 phosphorus Substances 0.000 claims 2
230000003098 cholesteric effect Effects 0.000 claims 1
230000000087 stabilizing effect Effects 0.000 claims 1
238000005538 encapsulation Methods 0.000 abstract 1
239000006185 dispersion Substances 0.000 description 29
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 10
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
MWWSFMDVAYGXBV-RUELKSSGSA-N Doxorubicin hydrochloride Chemical compound Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 MWWSFMDVAYGXBV-RUELKSSGSA-N 0.000 description 8
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
229960002918 doxorubicin hydrochloride Drugs 0.000 description 8
238000004945 emulsification Methods 0.000 description 6
150000002500 ions Chemical class 0.000 description 6
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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 description 5
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VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
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BIABMEZBCHDPBV-MPQUPPDSSA-N 1,2-palmitoyl-sn-glycero-3-phospho-(1'-sn-glycerol) Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@@H](O)CO)OC(=O)CCCCCCCCCCCCCCC BIABMEZBCHDPBV-MPQUPPDSSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
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OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
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CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
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229960005160 dimyristoylphosphatidylglycerol Drugs 0.000 description 3
BPHQZTVXXXJVHI-AJQTZOPKSA-N ditetradecanoyl phosphatidylglycerol Chemical compound CCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@@H](O)CO)OC(=O)CCCCCCCCCCCCC BPHQZTVXXXJVHI-AJQTZOPKSA-N 0.000 description 3
235000013345 egg yolk Nutrition 0.000 description 3
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239000011521 glass Substances 0.000 description 3
235000011187 glycerol Nutrition 0.000 description 3
239000000203 mixture Substances 0.000 description 3
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 description 3
239000005720 sucrose Substances 0.000 description 3
150000005846 sugar alcohols Polymers 0.000 description 3
WEEMDRWIKYCTQM-UHFFFAOYSA-N 2,6-dimethoxybenzenecarbothioamide Chemical compound COC1=CC=CC(OC)=C1C(N)=S WEEMDRWIKYCTQM-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
241000700159 Rattus Species 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
239000003963 antioxidant agent Substances 0.000 description 2
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238000002144 chemical decomposition reaction Methods 0.000 description 2
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238000011049 filling Methods 0.000 description 2
238000004108 freeze drying Methods 0.000 description 2
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238000003860 storage Methods 0.000 description 2
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
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GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
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GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 2
NAALWFYYHHJEFQ-ZASNTINBSA-N (2s,5r,6r)-6-[[(2r)-2-[[6-[4-[bis(2-hydroxyethyl)sulfamoyl]phenyl]-2-oxo-1h-pyridine-3-carbonyl]amino]-2-(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound N([C@@H](C(=O)N[C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C=1C=CC(O)=CC=1)C(=O)C(C(N1)=O)=CC=C1C1=CC=C(S(=O)(=O)N(CCO)CCO)C=C1 NAALWFYYHHJEFQ-ZASNTINBSA-N 0.000 description 1
RBNPOMFGQQGHHO-UHFFFAOYSA-N -2,3-Dihydroxypropanoic acid Natural products OCC(O)C(O)=O RBNPOMFGQQGHHO-UHFFFAOYSA-N 0.000 description 1
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 description 1
NRJAVPSFFCBXDT-HUESYALOSA-N 1,2-distearoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCC NRJAVPSFFCBXDT-HUESYALOSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 1
YWMSSKBMOFPBDM-UHFFFAOYSA-N 4-carbamoylbenzenesulfonyl chloride Chemical compound NC(=O)C1=CC=C(S(Cl)(=O)=O)C=C1 YWMSSKBMOFPBDM-UHFFFAOYSA-N 0.000 description 1
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FVJZSBGHRPJMMA-IOLBBIBUSA-N PG(18:0/18:0) Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@@H](O)CO)OC(=O)CCCCCCCCCCCCCCCCC FVJZSBGHRPJMMA-IOLBBIBUSA-N 0.000 description 1
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238000005199 ultracentrifugation Methods 0.000 description 1
239000002076 α-tocopherol Substances 0.000 description 1
235000004835 α-tocopherol Nutrition 0.000 description 1

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
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Epidemiology (AREA)
Dispersion Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Organic Chemistry (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Medicinal Preparation (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Manufacturing Of Micro-Capsules (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Formation And Processing Of Food Products (AREA)
Processes Of Treating Macromolecular Substances (AREA)

JP3199794A 1990-07-16 1991-07-16 リポソーム製剤 Expired - Fee Related JP2609183B2 (ja)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
JP3199794A JP2609183B2 (ja)	1990-07-16	1991-07-16	リポソーム製剤

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
JP18737090		1990-07-16
JP2-187370		1990-07-16
JP3199794A JP2609183B2 (ja)	1990-07-16	1991-07-16	リポソーム製剤

Publications (2)

Publication Number	Publication Date
JPH05194191A JPH05194191A (ja)	1993-08-03
JP2609183B2 true JP2609183B2 (ja)	1997-05-14

Family

ID=16204819

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP3199794A Expired - Fee Related JP2609183B2 (ja)	1990-07-16	1991-07-16	リポソーム製剤

Country Status (11)

Country	Link
EP (1)	EP0467275B1 (2)
JP (1)	JP2609183B2 (2)
KR (1)	KR100223129B1 (2)
AT (1)	ATE144415T1 (2)
CA (1)	CA2046997C (2)
DE (1)	DE69122810T2 (2)
DK (1)	DK0467275T3 (2)
ES (1)	ES2097168T3 (2)
GR (1)	GR3021982T3 (2)
HU (1)	HU211991A9 (2)
TW (1)	TW205510B (2)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ES2041597B1 (es) *	1992-05-05	1994-06-01	Bazaco Joan Freixas	Nuevo procedimiento para la preparacion de liposomas que encapsulan productos farmaceuticos y cosmeticos.
US5464696A (en) *	1992-08-13	1995-11-07	Bracco International B.V.	Particles for NMR imaging
CA2120197A1 (en) *	1993-04-02	1994-10-03	Kenji Endo	Stable aqueous dispersions containing liposomes
CZ128096A3 (en) *	1993-11-04	1997-08-13	Schering Ag	Charged liposome preparation
DE19639811A1 (de) *	1996-09-27	1998-04-02	Artur Herzog Dr Mesmer	Verwendung einer Liposomenlösung zur Verstärkung der Wirksamkeit und/oder Verminderung der Toxizität von Arzneimitteln
EP1190705A4 (en) *	1999-06-24	2009-03-18	Kyowa Hakko Kogyo Kk	METHOD FOR REGULATING THE LEAKAGE OF ENCAPSULATED MEDICINES IN LIPOSOMES
US7179484B2 (en) *	2002-11-06	2007-02-20	Azaya Therapeutics, Inc.	Protein-stabilized liposomal formulations of pharmaceutical agents
KR100965088B1 (ko) *	2004-12-07	2010-06-23	(주)아모레퍼시픽	유효성분의 안정화를 위한 다층 라멜라 베지클 및 그제조방법
GR20060100144A (el) *	2006-03-03	2007-10-17		Θεραπεια του καρκινου με χρηση οξαλιπλατινης εγκλεισμενης μεσα σε λιποσωματα και απο κοινου εγκλεισμος στο λιποσωμιακο μοριο περισσοτερων απο ενος φαρμακευτικου παρασκευασματος h gene
ES2325901B1 (es) *	2008-02-20	2010-07-06	Heber Farma Sl	Vehiculizacion del factor de crecimiento epidermico a traves de biomembranas.

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4419348A (en) *	1981-04-27	1983-12-06	Georgetown University	Anthracycline glycoside compositions, their use and preparation
IE58981B1 (en) *	1985-10-15	1993-12-15	Vestar Inc	Anthracycline antineoplastic agents encapsulated in phospholipid micellular particles
JPH0617309B2 (ja) *	1985-11-29	1994-03-09	株式会社ビタミン研究所	アドリアマイシン包埋リポソ−ム製剤
US4797285A (en) *	1985-12-06	1989-01-10	Yissum Research And Development Company Of The Hebrew University Of Jerusalem	Lipsome/anthraquinone drug composition and method
EP0498471B1 (en) *	1986-12-23	1996-08-14	The Liposome Company, Inc.	Liposomes comprising a guanidino aminoglycoside

1991
- 1991-07-12 CA CA002046997A patent/CA2046997C/en not_active Expired - Fee Related
- 1991-07-15 TW TW080105474A patent/TW205510B/zh active
- 1991-07-15 AT AT91111795T patent/ATE144415T1/de not_active IP Right Cessation
- 1991-07-15 EP EP91111795A patent/EP0467275B1/en not_active Expired - Lifetime
- 1991-07-15 DE DE69122810T patent/DE69122810T2/de not_active Expired - Fee Related
- 1991-07-15 DK DK91111795.0T patent/DK0467275T3/da active
- 1991-07-15 ES ES91111795T patent/ES2097168T3/es not_active Expired - Lifetime
- 1991-07-16 KR KR1019910012144A patent/KR100223129B1/ko not_active Expired - Fee Related
- 1991-07-16 JP JP3199794A patent/JP2609183B2/ja not_active Expired - Fee Related
1995
- 1995-06-22 HU HU95P/P00406P patent/HU211991A9/hu unknown
1996
- 1996-12-11 GR GR960403415T patent/GR3021982T3/el unknown

Also Published As

Publication number	Publication date
GR3021982T3 (en)	1997-03-31
KR920002165A (ko)	1992-02-28
ES2097168T3 (es)	1997-04-01
DE69122810D1 (de)	1996-11-28
DE69122810T2 (de)	1997-05-28
EP0467275B1 (en)	1996-10-23
ATE144415T1 (de)	1996-11-15
TW205510B (2)	1993-05-11
JPH05194191A (ja)	1993-08-03
DK0467275T3 (2)	1997-02-17
HU211991A9 (en)	1996-01-29
CA2046997A1 (en)	1992-01-17
EP0467275A1 (en)	1992-01-22
KR100223129B1 (ko)	1999-10-15
CA2046997C (en)	2000-12-12

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