DK157060B - Fremgangsmaade til fremstilling af en liposomsuspension, der indeholder et laegemiddel - Google Patents
Fremgangsmaade til fremstilling af en liposomsuspension, der indeholder et laegemiddel Download PDFInfo
- Publication number
- DK157060B DK157060B DK022380AA DK22380A DK157060B DK 157060 B DK157060 B DK 157060B DK 022380A A DK022380A A DK 022380AA DK 22380 A DK22380 A DK 22380A DK 157060 B DK157060 B DK 157060B
- Authority
- DK
- Denmark
- Prior art keywords
- liposome suspension
- preparing
- drug
- suspension
- suspension containing
- Prior art date
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- 239000000725 suspension Substances 0.000 title claims description 25
- 238000000034 method Methods 0.000 title description 8
- 239000002502 liposome Substances 0.000 claims description 25
- 239000011347 resin Substances 0.000 claims description 13
- 229920005989 resin Polymers 0.000 claims description 13
- 229940079593 drug Drugs 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- 229920003303 ion-exchange polymer Polymers 0.000 claims description 8
- 239000003456 ion exchange resin Substances 0.000 claims description 7
- 238000004108 freeze drying Methods 0.000 claims description 6
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 4
- 150000002632 lipids Chemical class 0.000 claims description 4
- LJRDOKAZOAKLDU-UDXJMMFXSA-N (2s,3s,4r,5r,6r)-5-amino-2-(aminomethyl)-6-[(2r,3s,4r,5s)-5-[(1r,2r,3s,5r,6s)-3,5-diamino-2-[(2s,3r,4r,5s,6r)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-hydroxycyclohexyl]oxy-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]oxyoxane-3,4-diol;sulfuric ac Chemical compound OS(O)(=O)=O.N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)O[C@@H]1CO LJRDOKAZOAKLDU-UDXJMMFXSA-N 0.000 claims description 3
- 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 claims description 3
- 239000003463 adsorbent Substances 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 238000007664 blowing Methods 0.000 claims description 3
- 229960002918 doxorubicin hydrochloride Drugs 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 2
- 238000001704 evaporation Methods 0.000 claims description 2
- 230000008020 evaporation Effects 0.000 claims description 2
- 229960002949 fluorouracil Drugs 0.000 claims description 2
- 239000011261 inert gas Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 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 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 230000002209 hydrophobic effect Effects 0.000 description 4
- 235000012000 cholesterol Nutrition 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin 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-TZSSRYMLSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- -1 cholesterol Chemical class 0.000 description 2
- RNPXCFINMKSQPQ-UHFFFAOYSA-N dicetyl hydrogen phosphate Chemical compound CCCCCCCCCCCCCCCCOP(O)(=O)OCCCCCCCCCCCCCCCC RNPXCFINMKSQPQ-UHFFFAOYSA-N 0.000 description 2
- 229940093541 dicetylphosphate Drugs 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000000527 sonication Methods 0.000 description 2
- 238000005199 ultracentrifugation Methods 0.000 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 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 238000005411 Van der Waals force Methods 0.000 description 1
- 229940114077 acrylic acid Drugs 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- ZAKOWWREFLAJOT-UHFFFAOYSA-N d-alpha-Tocopheryl acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-UHFFFAOYSA-N 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- UCQFCFPECQILOL-UHFFFAOYSA-N diethyl hydrogen phosphate Chemical compound CCOP(O)(=O)OCC UCQFCFPECQILOL-UHFFFAOYSA-N 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229920013730 reactive polymer Polymers 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 229940042585 tocopherol acetate Drugs 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 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
- A61K9/1277—Preparation processes; Proliposomes
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Dispersion Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
DK 157060 B
Den foreliggende opfindelse angâr en fremgangsmâde til fremstilling af en 1iposomsuspension, der indeholder et lægemiddel, som kan være doxorubicin-hydrochlorid, aminosi-dinsulfat eller 5-fluor-uracil.
5 Fremgangsmâden if0lge opfindelsen er ejendommelig ved, at man a) fremstiller en liposomsuspension ved opl0snng af lipid-bestanddele i et opl0sningsmiddel, tilsætter en vandig op-l0sning af lægemidlet og emulgerer ved indblæsning af en 10 indifferent gas, indtil opl0snîngsmidlet er fjernet fuld-stændigt ved fordampning, b) renser liposomsuspensionen ved behandling deraf med en polymer ionbytterharpiks eller en polymer adsorberende har-piks og eventuelt 15 c) stabiliserer den rensede suspension ved frystet0rring.
Liposomer er pharmaceutiske saitunensætninger, hvori lægemidlet enten er dispergeret eller i anden form forekommer som smâ kugler, der bestâr af vandige koncentriske lag, der hæfter til lipide (hydrophobe) lag; lægemidlet kan forekomme 20 bâde i det vandige lag og i lipidlaget (indvendigt eller udvendigt) eller hvorsomhelst i det dishomogene, i reglen som liposomsuspension kendte System.
Det hydrophobe lag indeholder i reglen, men ikke udelukkende, phospholipider sâsom lecithin og sphingomyelin, 25 steroider sâsom cholestérol, flere eller færre ionogene overfladeaktive stoffer sâsom dicetylphosphat, stearylamin eller phosphatidinsyre og/eller et andet materiale af hydro-phob karakter. Liposomernes diameter ligger i reglen mellem 15 nm og 5 jum.
30 Fremgangsmâden til fremstilling heraf foregâr i reglen pâ kendt mâde og omfatter to hovedtrin: 1) Fremstilling af liposomerne, hvor de lipide eller lipophile komponenter oploses i et egnet oplosningsmiddel, som derefter i reglen i vakuum afdampes til torhed.
35 Det vandige lag, der indeholder lægemidlet, sættes til kolben, der indeholder remanensen som et tyndt lag, og 2
DK 157060B
det hele underkastes derefter i et tidsrum pâ fra 10 sekun-der til nogle timer emulgering ved indblæsning af en indifferent gas. Det herved fremkomne inhomogene lag, i régien kaldet liposomsuspension, skal renses for fysisk ikke-bundet 5 lægemiddel.
2) Fraskillelse af liposomerne fra fysisk ikke-bundet lægemiddel: denne fremgangsmâde sker sædvanligvis ved elue-ring pâ en chromatografisk kolonne under anvendelse af har-pikser, der udelukkende har funktion som molekylarsigte, 10 sâsom "Sepharose"® 2B, 4B eller 6B og lignende.
Liposomerne udvindes ferst, medens det frie lægemiddel holdes tilbage af harpiksen.
Derefter felger en ultracentrifugeringsbehandling ved 100.000 g og derefter vaskes der, stadig ved hjælp af 15 ultracentrifugering med pufret oplosning. En anden metode, der kan anvendes, er dialyse.
Den foreliggende opfindelse angâr sâledes en særegen fremgangsmâde til rensning af det uhomogene, som liposomsuspension kendte lag sâvel ved hjælp af flydende som faste, 20 syntetiske eller organiske, reaktionsdygtige polymère, der kan anvendes som ionbyttere, sâsom polystyren, -divinylben-zen, -acryl- eller -methacrylsyre, der er kendte ionbytter-harpikser.
Den nojagtige mængde af en eller flere af de oven-25 nævnte harpikser indfores direkte i kolben, der indeholder liposomsuspensionen, der skal renses, hvorpâ der rystes i 10-60 minutter. Efter filtrering gennem et sinterglasfilter, der indeholder ionbytterharpiksen med absorberet fysisk ikke-bundet lægemiddel, fâs den rene liposomsuspension, der 30 kan frysetorres. Denne fremgangsmâde til rensning af liposomsuspensionen med ionbytterharpikser har den store fordel, at stærkt koncentrerede liposomsuspensioner (indtil 5 mg/ml doxorubicin*HCl) kan bibeholdes, hvilket ikke er tilfældet med chromatografi pâ en molekylær-sigtekolonne (maks, 0,3 35 mg/ml). Den sâledes opnâede liposomsuspension er meget stabil og har ingen tendens til sedimentering, sâledes som det er
DK 157060B
3 tilfældet med suspensioner, der fâs ved ultracentrifugering.
Det samme résultat opnâs, nâr man i stedet for ion-bytterharpikser anvendes polymère og copolymere uden nogen specifik kemisk funktion, der i reglen, men ikke udelukkende 5 reagerer pâ grund af Van der Waals-kræfter og i reglen er kendt soin adsorberende harpikser. Disse harpikser kan som f0lge af polaritetsforskellen mellem de hydrophobe stoffer, der danner liposomovertrækkene, og lægemidleme af mere eller mindre hydrophil natur anvendes ved rensningen af 10 liposomsuspensioner.
Den endelige kemiske stabilisering opnâs ved fryse-t0rring af liposomsuspensionen.
Eksempel 1 15 1,5 g sojalecithin, 0,4 g cholestérol og 0,3 g dice- tylphosphat oploses i CH2CI2, og til denne oplesning sættes en vandig opl0sning af aminosidinsulfat i 0,02 molær phos-phatpuffer ved 6,5 i en koncentration pâ 3 mg/ml.
Begge faser emulgeres ved indblæsning af nitrogen 20 ved stuetemperatur, indtil methylenchloridet er helt fjemet.
Suspensionen stabiliseres i 4 timer ved stuetemperatur, hvorpâ der i kolben hældes en mængde harpiks, der svarer til 5 g t0rharpiks, som fâs i handelen under betegnelsen "IRC-SO"®, en polymer kornformig harpiks, fra firmaet Rohm 25 og Haas.
Efter 1 times rÿsten filtreres liposomsuspensionen gennem en glasfritte for at fjerne harpiksen, der tilbage-holder det fysisk ikke-bundne lægemiddel. Derefter stabiliseres liposomsuspensionen ved hjælp af frysetorring.
30
Eksempel 2 3,22 g lecithin, 1,13 g cholestérol, 0,956 g dicetyl-phosphat og 16 mg vitamin E-acetat oploses i en lille mængde methylenchlorid. 448 mg doxorubicin-hydrochlorid og 7,77 g 35 lactose opl0ses i en pufferoplosning med pH = 5,6 (0,066 M natriumphosphat, 0,0388 M NaCl og 0,1 mM EDTA-dinatriumsalt).
DK 157060 B
4
Den organisée og den vandige opl0sning blandes ved rystning.
Derpâ bobles nitrogen igennem ved stuetemperatur, indtil methylenchloridet er helt fjernet. Suspensionen underkastes derefter lydbehandling ved, at den anbringes i en lydbehand-5 lingssonde, hvorpâ der i kolben hældes 80 g (vâd) ionbytter-harpiks "IRC-SO"®, en polymer kornformig harpiks, der fâs fra Rohm og Haas.
Efter 1 times rystning fjernes harpiksen ved filtre-ring, og liposomsuspensionen filtreres igen gennem et mem-10 branfilter med en poresitet pâ 3 μη. Liposomsuspensionen fordeles derpâ i hætteglas, anbringes i et frysetorringsap-parat og underkastes frysetorring.
Claims (1)
- DK 157060B Patentkrav . Fremgangsmâde til fremstilling af en liposomsuspen-sion, der indeholder et lægemiddel, som kan være doxorubicin-hydrochlorid, aminosidinsulfat eller 5-fluor-uracil, k e n-5 detegnet ved, at man a) fremstiller en liposomsuspension ved opl0snng af lipid-bestanddele i et opl0sningsmiddel/ tilsaetter en vandig op-l0sning af lægemidlet og emulgerer ved indblæsning af en indifferent gasf indtil opl0sningsmidlet er fjernet fuld- 10 stændigt ved fordampning, b) renser liposomsuspensionen ved behandling deraf med en polymer ionbytterharpiks eller en polymer adsorberende har-piks og eventuelt c) stabiliserer dën rensede suspension ved frystetorring.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT1943479 | 1979-01-19 | ||
| IT19434/79A IT1110989B (it) | 1979-01-19 | 1979-01-19 | Forme farmaceutiche costitutite da liposomi e procedimenti relativi |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK22380A DK22380A (da) | 1980-07-20 |
| DK157060B true DK157060B (da) | 1989-11-06 |
| DK157060C DK157060C (da) | 1990-04-09 |
Family
ID=11157905
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK022380A DK157060C (da) | 1979-01-19 | 1980-01-18 | Fremgangsmaade til fremstilling af en liposomsuspension, der indeholder et laegemiddel |
Country Status (21)
| Country | Link |
|---|---|
| JP (1) | JPS55100313A (da) |
| AT (1) | AT370623B (da) |
| AU (1) | AU536823B2 (da) |
| BE (1) | BE881225A (da) |
| CA (1) | CA1148470A (da) |
| CH (1) | CH648205A5 (da) |
| CS (1) | CS227010B2 (da) |
| DE (1) | DE3001842A1 (da) |
| DK (1) | DK157060C (da) |
| FI (1) | FI70672C (da) |
| FR (1) | FR2446635B1 (da) |
| GB (1) | GB2041871B (da) |
| HU (1) | HU184714B (da) |
| IE (1) | IE49141B1 (da) |
| IL (1) | IL59120A (da) |
| IT (1) | IT1110989B (da) |
| NL (1) | NL8000139A (da) |
| SE (1) | SE445171B (da) |
| SU (1) | SU1367839A3 (da) |
| YU (1) | YU44003B (da) |
| ZA (1) | ZA80269B (da) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU184141B (en) * | 1979-12-27 | 1984-07-30 | Human Oltoanyagtermelo | Adjuvant particles compositions containing said particles and biologically active substances adsorbed thereon and a process for the preparation thereof |
| FR2521565B1 (fr) * | 1982-02-17 | 1985-07-05 | Dior Sa Parfums Christian | Melange pulverulent de constituants lipidiques et de constituants hydrophobes, procede pour le preparer, phases lamellaires lipidiques hydratees et procede de fabrication, compositions pharmaceutiques ou cosmetiques comportant des phases lamellaires lipidiques hydratees |
| FR2553002B1 (fr) * | 1983-10-06 | 1992-03-27 | Centre Nat Rech Scient | Procede perfectionne d'obtention de liposomes unilamellaires de diametres eleves, leur application pharmacologique pour l'encapsulage d'un principe actif en vue de son administration extemporanee et dispositif correspondant |
| CA1270198A (en) * | 1984-08-08 | 1990-06-12 | Marcel B. Bally | Encapsulation of antineoplastic agents in liposomes |
| US5736155A (en) * | 1984-08-08 | 1998-04-07 | The Liposome Company, Inc. | Encapsulation of antineoplastic agents in liposomes |
| US4755388A (en) * | 1984-11-09 | 1988-07-05 | The Regents Of The University Of California | Liposome-encapsulated 5-fluoropyrimidines and methods for their use |
| IL79114A (en) * | 1985-08-07 | 1990-09-17 | Allergan Pharma | Method and composition for making liposomes |
| US6406713B1 (en) * | 1987-03-05 | 2002-06-18 | The Liposome Company, Inc. | Methods of preparing low-toxicity drug-lipid complexes |
| AU660288B2 (en) * | 1990-07-31 | 1995-06-22 | Transave, Inc. | Accumulation of amino acids and peptides into liposomes |
| DE4107152C2 (de) * | 1991-03-06 | 1994-03-24 | Gregor Cevc | Präparate zur nichtinvasiven Verabreichung von Antidiabetica |
| DE4107153A1 (de) * | 1991-03-06 | 1992-09-10 | Gregor Cevc | Praeparat zur wirkstoffapplikation in kleinsttroepfchenform |
| JPH04127874U (ja) * | 1991-05-13 | 1992-11-20 | 株式会社新潟鐵工所 | コンクリートポンプ用輸送管の圧送音緩和装置 |
| JPH04134673U (ja) * | 1991-06-07 | 1992-12-15 | 株式会社フジタ | コンクリート圧送圧変動防止装置 |
| AU676906B2 (en) * | 1993-04-02 | 1997-03-27 | Transave, Inc. | Method of producing liposomes |
| IT1270678B (it) * | 1994-10-20 | 1997-05-07 | Bayer Ag | Liposomi al chetoprofen |
| 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 |
| JP4283355B2 (ja) * | 1997-11-10 | 2009-06-24 | 久光製薬株式会社 | 薬剤用徐放化剤及びそれを含有した徐放性医薬組成物 |
| CA2309597A1 (en) * | 1997-11-10 | 1999-05-20 | Hiroshi Sorimachi | Sustainedly releasing agents for medicines and sustainedly released medicinal compositions containing the same |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK425478A (da) * | 1977-09-30 | 1979-03-31 | Farmaceutici Italia | Fremgangsmaade til fremstilling af injicerbare lipsomer |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2249552A1 (de) * | 1971-10-12 | 1973-05-30 | Inchema S A | Verfahren zur inkapsulation von insbesondere wasserloeslichen verbindungen |
| JPS5126213A (ja) * | 1974-08-21 | 1976-03-04 | Tanabe Seiyaku Co | Johoseibiryushiseizaino seiho |
| US4131815A (en) * | 1977-02-23 | 1978-12-26 | Oceanography International Corporation | Solid piezoelectric sand detection probes |
| GB1575343A (en) * | 1977-05-10 | 1980-09-17 | Ici Ltd | Method for preparing liposome compositions containing biologically active compounds |
-
1979
- 1979-01-19 IT IT19434/79A patent/IT1110989B/it active
-
1980
- 1980-01-09 NL NL8000139A patent/NL8000139A/nl not_active Application Discontinuation
- 1980-01-14 IL IL59120A patent/IL59120A/xx unknown
- 1980-01-14 JP JP219280A patent/JPS55100313A/ja active Granted
- 1980-01-14 AU AU54581/80A patent/AU536823B2/en not_active Ceased
- 1980-01-14 YU YU81/80A patent/YU44003B/xx unknown
- 1980-01-15 AT AT0019380A patent/AT370623B/de not_active IP Right Cessation
- 1980-01-15 FR FR808000801A patent/FR2446635B1/fr not_active Expired
- 1980-01-15 CS CS80309A patent/CS227010B2/cs unknown
- 1980-01-15 CA CA000343663A patent/CA1148470A/en not_active Expired
- 1980-01-16 ZA ZA00800269A patent/ZA80269B/xx unknown
- 1980-01-16 IE IE91/80A patent/IE49141B1/en unknown
- 1980-01-17 SU SU802869298A patent/SU1367839A3/ru active
- 1980-01-17 CH CH370/80A patent/CH648205A5/de not_active IP Right Cessation
- 1980-01-17 HU HU8097A patent/HU184714B/hu not_active IP Right Cessation
- 1980-01-17 GB GB8001545A patent/GB2041871B/en not_active Expired
- 1980-01-17 FI FI800151A patent/FI70672C/fi not_active IP Right Cessation
- 1980-01-18 BE BE0/199021A patent/BE881225A/fr not_active IP Right Cessation
- 1980-01-18 DK DK022380A patent/DK157060C/da not_active IP Right Cessation
- 1980-01-18 SE SE8000443A patent/SE445171B/sv not_active IP Right Cessation
- 1980-01-18 DE DE19803001842 patent/DE3001842A1/de active Granted
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK425478A (da) * | 1977-09-30 | 1979-03-31 | Farmaceutici Italia | Fremgangsmaade til fremstilling af injicerbare lipsomer |
Also Published As
| Publication number | Publication date |
|---|---|
| IE49141B1 (en) | 1985-08-07 |
| GB2041871B (en) | 1983-04-13 |
| AT370623B (de) | 1983-04-25 |
| YU44003B (en) | 1990-02-28 |
| BE881225A (fr) | 1980-07-18 |
| DK157060C (da) | 1990-04-09 |
| FI800151A7 (fi) | 1980-07-20 |
| CS227010B2 (en) | 1984-04-16 |
| AU5458180A (en) | 1980-07-24 |
| FI70672C (fi) | 1986-10-06 |
| DE3001842C2 (da) | 1990-04-26 |
| JPS55100313A (en) | 1980-07-31 |
| SE8000443L (sv) | 1980-07-20 |
| SU1367839A3 (ru) | 1988-01-15 |
| DK22380A (da) | 1980-07-20 |
| CH648205A5 (de) | 1985-03-15 |
| GB2041871A (en) | 1980-09-17 |
| SE445171B (sv) | 1986-06-09 |
| JPH0133446B2 (da) | 1989-07-13 |
| CA1148470A (en) | 1983-06-21 |
| NL8000139A (nl) | 1980-07-22 |
| ZA80269B (en) | 1981-06-24 |
| IE800091L (en) | 1980-07-19 |
| YU8180A (en) | 1983-12-31 |
| ATA19380A (de) | 1982-09-15 |
| DE3001842A1 (de) | 1980-07-31 |
| IL59120A0 (en) | 1980-05-30 |
| HU184714B (en) | 1984-10-29 |
| IL59120A (en) | 1984-05-31 |
| IT1110989B (it) | 1986-01-13 |
| FI70672B (fi) | 1986-06-26 |
| FR2446635A1 (fr) | 1980-08-14 |
| FR2446635B1 (fr) | 1989-03-10 |
| AU536823B2 (en) | 1984-05-24 |
| IT7919434A0 (it) | 1979-01-19 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PBP | Patent lapsed |