JPH09511762A - マイクロカプセル並びにその製造及び使用方法 - Google Patents
マイクロカプセル並びにその製造及び使用方法Info
- Publication number
- JPH09511762A JPH09511762A JP8516715A JP51671596A JPH09511762A JP H09511762 A JPH09511762 A JP H09511762A JP 8516715 A JP8516715 A JP 8516715A JP 51671596 A JP51671596 A JP 51671596A JP H09511762 A JPH09511762 A JP H09511762A
- Authority
- JP
- Japan
- Prior art keywords
- microcapsules
- acid
- mixture
- biodegradable
- microcapsule
- 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.)
- Granted
Links
- 239000003094 microcapsule Substances 0.000 title claims abstract description 158
- 238000004519 manufacturing process Methods 0.000 title claims description 13
- 239000000203 mixture Substances 0.000 claims abstract description 63
- PVNIQBQSYATKKL-UHFFFAOYSA-N tripalmitin Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCC PVNIQBQSYATKKL-UHFFFAOYSA-N 0.000 claims abstract description 63
- 150000002632 lipids Chemical class 0.000 claims abstract description 39
- DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 claims abstract description 34
- 229960001947 tripalmitin Drugs 0.000 claims abstract description 31
- 239000013543 active substance Substances 0.000 claims abstract description 25
- 229920002988 biodegradable polymer Polymers 0.000 claims abstract description 24
- 239000004621 biodegradable polymer Substances 0.000 claims abstract description 24
- 238000000034 method Methods 0.000 claims abstract description 23
- 239000012528 membrane Substances 0.000 claims abstract description 19
- 239000002872 contrast media Substances 0.000 claims abstract description 14
- 239000004094 surface-active agent Substances 0.000 claims abstract description 14
- 239000002904 solvent Substances 0.000 claims abstract description 10
- 238000001704 evaporation Methods 0.000 claims abstract description 7
- 239000008365 aqueous carrier Substances 0.000 claims abstract description 6
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000003384 imaging method Methods 0.000 claims abstract description 5
- 125000005456 glyceride group Chemical group 0.000 claims description 24
- 239000002775 capsule Substances 0.000 claims description 21
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 21
- 239000000194 fatty acid Substances 0.000 claims description 21
- 229930195729 fatty acid Natural products 0.000 claims description 21
- -1 Di-glyceride Chemical compound 0.000 claims description 19
- 150000004665 fatty acids Chemical class 0.000 claims description 18
- 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 description 14
- 239000003960 organic solvent Substances 0.000 claims description 14
- 239000007787 solid Substances 0.000 claims description 13
- 229930182558 Sterol Natural products 0.000 claims description 12
- 235000003702 sterols Nutrition 0.000 claims description 12
- 239000002245 particle Substances 0.000 claims description 11
- 150000003432 sterols Chemical class 0.000 claims description 11
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 claims description 10
- DUXYWXYOBMKGIN-UHFFFAOYSA-N trimyristin Chemical compound CCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCC DUXYWXYOBMKGIN-UHFFFAOYSA-N 0.000 claims description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 239000008346 aqueous phase Substances 0.000 claims description 9
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 8
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 8
- 239000007764 o/w emulsion Substances 0.000 claims description 8
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 8
- 229920001400 block copolymer Polymers 0.000 claims description 7
- 235000012000 cholesterol Nutrition 0.000 claims description 7
- 150000002148 esters Chemical class 0.000 claims description 7
- 150000003904 phospholipids Chemical class 0.000 claims description 7
- 239000000843 powder Substances 0.000 claims description 7
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 6
- 229920001577 copolymer Polymers 0.000 claims description 6
- CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical compound OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 claims description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 6
- 235000021314 Palmitic acid Nutrition 0.000 claims description 5
- 235000021355 Stearic acid Nutrition 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 claims description 5
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 5
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 5
- 239000012071 phase Substances 0.000 claims description 5
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 239000003381 stabilizer Substances 0.000 claims description 5
- 239000008117 stearic acid Substances 0.000 claims description 5
- 229940113164 trimyristin Drugs 0.000 claims description 5
- 238000002604 ultrasonography Methods 0.000 claims description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- 102000004877 Insulin Human genes 0.000 claims description 4
- 108090001061 Insulin Proteins 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 239000000654 additive Substances 0.000 claims description 4
- 229950005499 carbon tetrachloride Drugs 0.000 claims description 4
- WJTCGQSWYFHTAC-UHFFFAOYSA-N cyclooctane Chemical compound C1CCCCCCC1 WJTCGQSWYFHTAC-UHFFFAOYSA-N 0.000 claims description 4
- 239000004914 cyclooctane Substances 0.000 claims description 4
- UKMSUNONTOPOIO-UHFFFAOYSA-N docosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCC(O)=O UKMSUNONTOPOIO-UHFFFAOYSA-N 0.000 claims description 4
- 230000008014 freezing Effects 0.000 claims description 4
- 238000007710 freezing Methods 0.000 claims description 4
- VKOBVWXKNCXXDE-UHFFFAOYSA-N icosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCC(O)=O VKOBVWXKNCXXDE-UHFFFAOYSA-N 0.000 claims description 4
- 239000007972 injectable composition Substances 0.000 claims description 4
- 229940125396 insulin Drugs 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 239000011148 porous material Substances 0.000 claims description 4
- 229960005205 prednisolone Drugs 0.000 claims description 4
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 claims description 4
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 4
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 4
- UGCSPKPEHQEOSR-UHFFFAOYSA-N 1,1,2,2-tetrachloro-1,2-difluoroethane Chemical compound FC(Cl)(Cl)C(F)(Cl)Cl UGCSPKPEHQEOSR-UHFFFAOYSA-N 0.000 claims description 3
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 claims description 3
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 claims description 3
- 108010088751 Albumins Proteins 0.000 claims description 3
- 102000009027 Albumins Human genes 0.000 claims description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 3
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 claims description 3
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 claims description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 3
- 229920000954 Polyglycolide Polymers 0.000 claims description 3
- 229930003427 Vitamin E Natural products 0.000 claims description 3
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 3
- 150000008282 halocarbons Chemical class 0.000 claims description 3
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 3
- 229920002627 poly(phosphazenes) Polymers 0.000 claims description 3
- 229920001184 polypeptide Polymers 0.000 claims description 3
- 229960002052 salbutamol Drugs 0.000 claims description 3
- 235000019165 vitamin E Nutrition 0.000 claims description 3
- 229940046009 vitamin E Drugs 0.000 claims description 3
- 239000011709 vitamin E Substances 0.000 claims description 3
- 239000008096 xylene Substances 0.000 claims description 3
- 235000021357 Behenic acid Nutrition 0.000 claims description 2
- DPUOLQHDNGRHBS-UHFFFAOYSA-N Brassidinsaeure Natural products CCCCCCCCC=CCCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-UHFFFAOYSA-N 0.000 claims description 2
- URXZXNYJPAJJOQ-UHFFFAOYSA-N Erucic acid Natural products CCCCCCC=CCCCCCCCCCCCC(O)=O URXZXNYJPAJJOQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000002616 MRI contrast agent Substances 0.000 claims description 2
- 229920002732 Polyanhydride Polymers 0.000 claims description 2
- 229920000331 Polyhydroxybutyrate Polymers 0.000 claims description 2
- 150000001335 aliphatic alkanes Chemical group 0.000 claims description 2
- 210000001557 animal structure Anatomy 0.000 claims description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 2
- 229940116226 behenic acid Drugs 0.000 claims description 2
- 150000001924 cycloalkanes Chemical class 0.000 claims description 2
- 238000009826 distribution Methods 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 230000001804 emulsifying effect Effects 0.000 claims description 2
- DPUOLQHDNGRHBS-KTKRTIGZSA-N erucic acid Chemical compound CCCCCCCC\C=C/CCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-KTKRTIGZSA-N 0.000 claims description 2
- 229940068065 phytosterols Drugs 0.000 claims description 2
- 229920001308 poly(aminoacid) Polymers 0.000 claims description 2
- 239000005015 poly(hydroxybutyrate) Substances 0.000 claims description 2
- 229920002463 poly(p-dioxanone) polymer Polymers 0.000 claims description 2
- 239000000622 polydioxanone Substances 0.000 claims description 2
- 239000011877 solvent mixture Substances 0.000 claims description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims 2
- TWJNQYPJQDRXPH-UHFFFAOYSA-N 2-cyanobenzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1C#N TWJNQYPJQDRXPH-UHFFFAOYSA-N 0.000 claims 2
- 235000021360 Myristic acid Nutrition 0.000 claims 2
- TUNFSRHWOTWDNC-UHFFFAOYSA-N Myristic acid Natural products CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 claims 2
- GGCILSXUAHLDMF-CQSZACIVSA-N 2-[[2-[(3r)-3-aminopiperidin-1-yl]-5-bromo-6-oxopyrimidin-1-yl]methyl]benzonitrile Chemical compound C1[C@H](N)CCCN1C1=NC=C(Br)C(=O)N1CC1=CC=CC=C1C#N GGCILSXUAHLDMF-CQSZACIVSA-N 0.000 claims 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 claims 1
- 125000004093 cyano group Chemical group *C#N 0.000 claims 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 claims 1
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 claims 1
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- 239000003814 drug Substances 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
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- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 description 1
- 229960001225 rifampicin Drugs 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
- 229960002256 spironolactone Drugs 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 235000007586 terpenes Nutrition 0.000 description 1
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
- 238000003325 tomography Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 238000012285 ultrasound imaging Methods 0.000 description 1
- 229940072690 valium Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
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- 235000013343 vitamin Nutrition 0.000 description 1
- 239000000341 volatile oil Substances 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0065—Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
-
- 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
- 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
- A61K9/5015—Organic compounds, e.g. fats, sugars
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Nutrition Science (AREA)
- Physics & Mathematics (AREA)
- Acoustics & Sound (AREA)
- Physiology (AREA)
- Radiology & Medical Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Preparation (AREA)
- Manufacturing Of Micro-Capsules (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.空気又は気体のコアを封入している生分解性膜を有する平均粒径が数分の 一μm〜1000μmの固体マイクロカプセルであって、該膜が、モノ−グリセリド 、ジ−グリセリド、トリ−グリセリド、脂肪酸、ステロール、ワックス及びこれ らの混合物から選ばれた一種又は二種以上の生分解可能な水不溶性で且つ室温で 固体の脂質を含むことを特徴とする固体マイクロカプセル。 2.グリセリドがモノ−、ジ−若しくはトリ−ミリスチン、−パルミチン若し くは−ステアリン又はこれらの混合物であり、好ましくはトリパルミチン又はト リステアリンである、請求の範囲第1項に記載のマイクロカプセル。 3.脂肪酸がアラキジン酸、ベヘン酸、パルミチン酸、ステアリン酸、セバシ ン酸、ミリスチン酸及びエルカ酸の中から選ばれ、好ましくはステアリン酸、パ ルミチン酸、セバシン酸及びミリスチン酸の中から選ばれる、請求の範囲第1項 に記載のマイクロカプセル。 4.ステロールがコレステロール、フィトステロール、ラノステロール、エル ゴステロール及びこれらステロールと請求の範囲第3項に記載の脂肪酸とのエス テルの中から選ばれ、好ましくはコレステロールである、請求の範囲第1項に記 載のマイクロカプセル。 5.膜が少なくとも部分的に結晶性又は半結晶性である、請求の範囲第1項に 記載のマイクロカプセル。 6.膜がさらに生分解性ポリマーを最高で75重量%、好ましくは最高で10重量 %含む、請求の範囲第1項又は第2項に記載のマイクロカプセル。 7.マイクロカプセルの平均粒径分布範囲が0.1μm〜100 μmである、請求 の範囲第1項、第2項又は第3項に記載のマイクロカ プセル。 8.マイクロカプセルが多孔質であって20〜2,000 nmの気孔を有する、請求の 範囲第1項、第2項又は第3項に記載のマイクロカプセル。 9.マイクロカプセルが非凝集性であり、乾燥しており、そして液状担体中で 簡単に分散させることができる、請求の範囲第1項に記載のマイクロカプセル。 10.マイクロカプセルがさらに再分散剤を含む、請求の範囲第9項に記載のマ イクロカプセル。 11.再分散剤がアルブミン、ポリビニルアルコール及びポリエチレングリコー ルの中から選ばれた、請求の範囲第10項に記載のマイクロカプセル。 12.生分解性ポリマーが最高で50重量%、好ましくは最高で20重量%、より好 ましくは 0.5〜10重量%の量で存在している、請求の範囲第3項に記載のマイク ロカプセル。 13.生分解性ポリマーが、ポリアミノ酸、ポリラクチド及びポリグリコリド及 びそれらのコポリマー、ラクチド及びラクトンのコポリマー、ポリペプチド、ポ リ(オルト)エステル、ポリジオキサノン、ポリ−β−アミノケトン、ポリホス ファゼン、ポリ無水物、ポリヒドロキシブチレート並びにポリアルキル(シアノ )アクリレートの中から選ばれた、請求の範囲第12項に記載のマイクロカプセル 。 14.マイクロカプセルがさらにポリオキシエチレン−ポリオキシプロピレン系 ブロックコポリマー及びリン脂質の中から選ばれた界面活性剤を含む、請求の範 囲第1項〜第13項のいずれか一項に記載のマイクロカプセル。 15.膜がさらに脂肪親和性の活性物質を含む、請求の範囲第1項〜第14項のい ずれか一項に記載のマイクロカプセル。 16.脂肪親和性の活性物質がビタミンE、プレドニソロン、クロラムフェニコ ールパルミテート及びサルブタモールの中から選ばれた、請求の範囲第15項に記 載のマイクロカプセル。 17.コアが非イオン性ヨウ素化造影剤又はMRI造影剤を含む、請求の範囲第 1項〜第15項のいずれか一項に記載のマイクロカプセル。 18.コアがインシュリンを含む、請求の範囲第1項〜第15項のいずれか一項に 記載のマイクロカプセル。 19.請求の範囲第17項に記載のマイクロカプセルを生理学的に許容できる担体 相に懸濁させることによる造影剤の製造方法。 20.請求の範囲第1項〜第15項のいずれか一項に記載のマイクロカプセルの有 効量を、通常の添加剤及び安定剤を含む医薬品として許容できる液状担体中に懸 濁状態で含む注射可能な組成物。 21.a)生分解性脂質を必要に応じて生分解性ポリマーと共に有機溶媒又は溶媒 混合物に溶解させる工程と、 b)水相を混合する工程と、 c)その混合物を乳化して水中油形乳濁液を形成する工程と、 d)再分散剤を添加する工程と、 e)凍結する工程と、 f)凍結乾燥して準球形又は球形のマイクロカプセルを含有する粉末を形成する 工程と、 g)該粉末を水性担体中で分散させる工程と、 h)空気又は気体を含有するマイクロカプセルとデブリスとをデカント法で分離 する工程と、 i)回収したマイクロカプセルを乾燥する工程 とを含むことを特徴とする、請求の範囲第1項〜第15項のいずれか一項に記載の 固体マイクロカプセルの製造方法。 22.水中油形乳濁液の形成後に有機溶媒の一部を蒸発させる、請求の範囲第21 項に記載の方法。 23.溶媒混合物が水溶性有機溶媒と水不溶性有機溶媒との混合物である、請求 の範囲第21項に記載の方法。 24.水不溶性有機溶媒がアルカン、シクロアルカン、芳香族炭化水素、エーテ ル及びハロゲン化炭化水素の中から選ばれる、請求の範囲第23項に記載の方法。 25.溶媒がトルエン、キシレン、シクロオクタン、シクロヘキサン、クロロホ ルム、テトラクロロメタン、ジフルオロテトラクロロエタン、ジブチルエーテル 、ジイソプロピルエーテル、イソブチルメチルケトン及びこれらの混合物の中か ら選ばれる、請求の範囲第24項に記載の方法。 26.界面活性剤がポリオキシエチレン−ポリオキシプロピレン系ブロックコポ リマー及びリン脂質の中から選ばれる、請求の範囲第21項に記載の方法。 27.脂質の溶液に脂肪親和性の活性物質を添加してから水相を混合する、請求 の範囲第21項に記載の方法。 28.人体又は動物の器官の超音波画像診断用の、請求の範囲第1項〜第15項の いずれか一項に記載のマイクロカプセル。 29.治療用として有効な注射可能な組成物の製造に用いるための、請求の範囲 第1項〜第17項のいずれか一項に記載のマイクロカプセル。 30.超音波診断用造影剤の製造に用いるための、請求の範囲第1項〜第15項の いずれか一項に記載のマイクロカプセル。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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EP94810660 | 1994-11-22 | ||
AT94810660.4 | 1994-11-22 | ||
PCT/IB1995/001029 WO1996015815A1 (en) | 1994-11-22 | 1995-11-21 | Microcapsules, method of making and their use |
Publications (2)
Publication Number | Publication Date |
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JPH09511762A true JPH09511762A (ja) | 1997-11-25 |
JP4202414B2 JP4202414B2 (ja) | 2008-12-24 |
Family
ID=8218339
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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JP51671596A Expired - Fee Related JP4202414B2 (ja) | 1994-11-22 | 1995-11-21 | マイクロカプセル並びにその製造及び使用方法 |
Country Status (20)
Country | Link |
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US (2) | US6333021B1 (ja) |
EP (1) | EP0755270B1 (ja) |
JP (1) | JP4202414B2 (ja) |
KR (1) | KR100416163B1 (ja) |
CN (1) | CN1066964C (ja) |
AT (1) | ATE337795T1 (ja) |
AU (1) | AU709240B2 (ja) |
CA (1) | CA2178602C (ja) |
CZ (1) | CZ291178B6 (ja) |
DE (1) | DE69535203T2 (ja) |
ES (1) | ES2271947T3 (ja) |
FI (1) | FI120081B (ja) |
HU (1) | HU226896B1 (ja) |
IL (1) | IL116081A (ja) |
MX (1) | MX9602697A (ja) |
NO (1) | NO315692B1 (ja) |
PL (1) | PL182989B1 (ja) |
RU (1) | RU2139046C1 (ja) |
WO (1) | WO1996015815A1 (ja) |
ZA (1) | ZA959941B (ja) |
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Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2002544155A (ja) * | 1999-05-07 | 2002-12-24 | ファルマソル ゲーエムベーハー | 流体および固体脂質の混合物を基礎とする脂質粒子、およびそれらを製造するための方法 |
JP2007070389A (ja) * | 2005-09-05 | 2007-03-22 | Shiyoufuu:Kk | 半球状中空マイクロカプセル |
JP4680012B2 (ja) * | 2005-09-05 | 2011-05-11 | 株式会社松風 | 半球状中空マイクロカプセル |
JP2008120780A (ja) * | 2006-11-13 | 2008-05-29 | Kazutoyo Kawasaki | 胃部検診用造影剤 |
JP2011528031A (ja) * | 2008-07-14 | 2011-11-10 | ポリーペイド リミテッド | 徐放性薬剤キャリア組成物 |
JP2015129128A (ja) * | 2008-07-14 | 2015-07-16 | ポリーペイド リミテッドPolypid Ltd. | 徐放性薬剤キャリア組成物 |
JP2016145217A (ja) * | 2008-07-14 | 2016-08-12 | ポリーペイド リミテッドPolypid Ltd. | 徐放性薬剤キャリア組成物 |
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FI120081B (fi) | 2009-06-30 |
EP0755270B1 (en) | 2006-08-30 |
US6333021B1 (en) | 2001-12-25 |
ATE337795T1 (de) | 2006-09-15 |
FI962917A (fi) | 1996-07-19 |
HU9601996D0 (en) | 1996-09-30 |
PL182989B1 (pl) | 2002-05-31 |
DE69535203T2 (de) | 2007-07-19 |
HU226896B1 (en) | 2010-01-28 |
CZ214096A3 (en) | 1996-10-16 |
JP4202414B2 (ja) | 2008-12-24 |
AU709240B2 (en) | 1999-08-26 |
HUT74912A (en) | 1997-03-28 |
CN1066964C (zh) | 2001-06-13 |
NO962843D0 (no) | 1996-07-05 |
AU3814495A (en) | 1996-06-17 |
DE69535203D1 (de) | 2006-10-12 |
CA2178602A1 (en) | 1996-05-30 |
FI962917A0 (fi) | 1996-07-19 |
PL315585A1 (en) | 1996-11-12 |
CZ291178B6 (cs) | 2003-01-15 |
US6403057B1 (en) | 2002-06-11 |
CN1139386A (zh) | 1997-01-01 |
MX9602697A (es) | 1998-06-28 |
KR100416163B1 (ko) | 2004-03-19 |
ZA959941B (en) | 1996-06-10 |
IL116081A0 (en) | 1996-01-31 |
ES2271947T3 (es) | 2007-04-16 |
WO1996015815A1 (en) | 1996-05-30 |
RU2139046C1 (ru) | 1999-10-10 |
EP0755270A1 (en) | 1997-01-29 |
NO962843L (no) | 1996-07-05 |
CA2178602C (en) | 2004-03-30 |
IL116081A (en) | 2003-04-10 |
NO315692B1 (no) | 2003-10-13 |
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