KR970701066A - 초음파 가스 현탁물의 저장 방법(Method of Storage of Ultrasonic Gas Suspensions) - Google Patents
초음파 가스 현탁물의 저장 방법(Method of Storage of Ultrasonic Gas Suspensions)Info
- Publication number
- KR970701066A KR970701066A KR1019960704432A KR19960704432A KR970701066A KR 970701066 A KR970701066 A KR 970701066A KR 1019960704432 A KR1019960704432 A KR 1019960704432A KR 19960704432 A KR19960704432 A KR 19960704432A KR 970701066 A KR970701066 A KR 970701066A
- Authority
- KR
- South Korea
- Prior art keywords
- suspension
- microbubbles
- gas
- suspension according
- membrane
- Prior art date
Links
- 239000000725 suspension Substances 0.000 title claims abstract description 30
- 238000000034 method Methods 0.000 title claims abstract 8
- 239000008365 aqueous carrier Substances 0.000 claims abstract description 4
- 239000000654 additive Substances 0.000 claims abstract 7
- 239000012528 membrane Substances 0.000 claims abstract 7
- 150000003904 phospholipids Chemical class 0.000 claims abstract 6
- 239000007788 liquid Substances 0.000 claims abstract 4
- 239000004094 surface-active agent Substances 0.000 claims abstract 4
- 239000002872 contrast media Substances 0.000 claims abstract 3
- 238000007710 freezing Methods 0.000 claims abstract 3
- 230000008014 freezing Effects 0.000 claims abstract 3
- 102000004169 proteins and genes Human genes 0.000 claims abstract 3
- 108090000623 proteins and genes Proteins 0.000 claims abstract 3
- 239000008280 blood Substances 0.000 claims abstract 2
- 210000004369 blood Anatomy 0.000 claims abstract 2
- 229920005615 natural polymer Polymers 0.000 claims abstract 2
- 239000003381 stabilizer Substances 0.000 claims abstract 2
- 229920001059 synthetic polymer Polymers 0.000 claims abstract 2
- 239000007789 gas Substances 0.000 claims 10
- 230000000996 additive effect Effects 0.000 claims 5
- 239000000203 mixture Substances 0.000 claims 5
- -1 phytosterol Chemical compound 0.000 claims 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims 3
- 229920001577 copolymer Polymers 0.000 claims 3
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- 229920000642 polymer Polymers 0.000 claims 3
- 239000010409 thin film Substances 0.000 claims 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims 2
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 claims 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 claims 2
- 238000001816 cooling Methods 0.000 claims 2
- 235000014113 dietary fatty acids Nutrition 0.000 claims 2
- 229930195729 fatty acid Natural products 0.000 claims 2
- 239000000194 fatty acid Substances 0.000 claims 2
- 150000004665 fatty acids Chemical class 0.000 claims 2
- 150000004676 glycans Polymers 0.000 claims 2
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 150000002367 halogens Chemical class 0.000 claims 2
- 229940102213 injectable suspension Drugs 0.000 claims 2
- 239000002609 medium Substances 0.000 claims 2
- 229920005862 polyol Polymers 0.000 claims 2
- 150000003077 polyols Chemical class 0.000 claims 2
- 235000000346 sugar Nutrition 0.000 claims 2
- 150000008163 sugars Chemical class 0.000 claims 2
- 238000012285 ultrasound imaging Methods 0.000 claims 2
- BQPPJGMMIYJVBR-UHFFFAOYSA-N (10S)-3c-Acetoxy-4.4.10r.13c.14t-pentamethyl-17c-((R)-1.5-dimethyl-hexen-(4)-yl)-(5tH)-Delta8-tetradecahydro-1H-cyclopenta[a]phenanthren Natural products CC12CCC(OC(C)=O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C BQPPJGMMIYJVBR-UHFFFAOYSA-N 0.000 claims 1
- OILXMJHPFNGGTO-UHFFFAOYSA-N (22E)-(24xi)-24-methylcholesta-5,22-dien-3beta-ol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(C)C(C)C)C1(C)CC2 OILXMJHPFNGGTO-UHFFFAOYSA-N 0.000 claims 1
- RQOCXCFLRBRBCS-UHFFFAOYSA-N (22E)-cholesta-5,7,22-trien-3beta-ol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CCC(C)C)CCC33)C)C3=CC=C21 RQOCXCFLRBRBCS-UHFFFAOYSA-N 0.000 claims 1
- CHGIKSSZNBCNDW-UHFFFAOYSA-N (3beta,5alpha)-4,4-Dimethylcholesta-8,24-dien-3-ol Natural products CC12CCC(O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21 CHGIKSSZNBCNDW-UHFFFAOYSA-N 0.000 claims 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 claims 1
- 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 1
- XYTLYKGXLMKYMV-UHFFFAOYSA-N 14alpha-methylzymosterol Natural products CC12CCC(O)CC1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C XYTLYKGXLMKYMV-UHFFFAOYSA-N 0.000 claims 1
- FPTJELQXIUUCEY-UHFFFAOYSA-N 3beta-Hydroxy-lanostan Natural products C1CC2C(C)(C)C(O)CCC2(C)C2C1C1(C)CCC(C(C)CCCC(C)C)C1(C)CC2 FPTJELQXIUUCEY-UHFFFAOYSA-N 0.000 claims 1
- OQMZNAMGEHIHNN-UHFFFAOYSA-N 7-Dehydrostigmasterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CC(CC)C(C)C)CCC33)C)C3=CC=C21 OQMZNAMGEHIHNN-UHFFFAOYSA-N 0.000 claims 1
- 102000009027 Albumins Human genes 0.000 claims 1
- 108010088751 Albumins Proteins 0.000 claims 1
- 239000004322 Butylated hydroxytoluene Substances 0.000 claims 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 claims 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims 1
- DNVPQKQSNYMLRS-NXVQYWJNSA-N Ergosterol Natural products CC(C)[C@@H](C)C=C[C@H](C)[C@H]1CC[C@H]2C3=CC=C4C[C@@H](O)CC[C@]4(C)[C@@H]3CC[C@]12C DNVPQKQSNYMLRS-NXVQYWJNSA-N 0.000 claims 1
- BKLIAINBCQPSOV-UHFFFAOYSA-N Gluanol Natural products CC(C)CC=CC(C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(O)C(C)(C)C4CC3 BKLIAINBCQPSOV-UHFFFAOYSA-N 0.000 claims 1
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 claims 1
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 claims 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Polymers OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims 1
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 claims 1
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 claims 1
- LOPKHWOTGJIQLC-UHFFFAOYSA-N Lanosterol Natural products CC(CCC=C(C)C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(C)(O)C(C)(C)C4CC3 LOPKHWOTGJIQLC-UHFFFAOYSA-N 0.000 claims 1
- CAHGCLMLTWQZNJ-UHFFFAOYSA-N Nerifoliol Natural products CC12CCC(O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C CAHGCLMLTWQZNJ-UHFFFAOYSA-N 0.000 claims 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims 1
- 229920002732 Polyanhydride Polymers 0.000 claims 1
- 229920000805 Polyaspartic acid Polymers 0.000 claims 1
- 108010020346 Polyglutamic Acid Proteins 0.000 claims 1
- 229920000954 Polyglycolide Polymers 0.000 claims 1
- 229920002396 Polyurea Polymers 0.000 claims 1
- 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 1
- 239000002253 acid Substances 0.000 claims 1
- 239000003570 air Substances 0.000 claims 1
- 150000001298 alcohols Chemical class 0.000 claims 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 claims 1
- 235000010385 ascorbyl palmitate Nutrition 0.000 claims 1
- 239000012298 atmosphere Substances 0.000 claims 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- 238000009835 boiling Methods 0.000 claims 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 claims 1
- 229940095259 butylated hydroxytoluene Drugs 0.000 claims 1
- 150000001720 carbohydrates Chemical class 0.000 claims 1
- 235000014633 carbohydrates Nutrition 0.000 claims 1
- 239000001569 carbon dioxide Substances 0.000 claims 1
- 229910002092 carbon dioxide Inorganic materials 0.000 claims 1
- 235000012000 cholesterol Nutrition 0.000 claims 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims 1
- RNPXCFINMKSQPQ-UHFFFAOYSA-N dicetyl hydrogen phosphate Chemical compound CCCCCCCCCCCCCCCCOP(O)(=O)OCCCCCCCCCCCCCCCC RNPXCFINMKSQPQ-UHFFFAOYSA-N 0.000 claims 1
- 229940093541 dicetylphosphate Drugs 0.000 claims 1
- QBSJHOGDIUQWTH-UHFFFAOYSA-N dihydrolanosterol Natural products CC(C)CCCC(C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(C)(O)C(C)(C)C4CC3 QBSJHOGDIUQWTH-UHFFFAOYSA-N 0.000 claims 1
- DNVPQKQSNYMLRS-SOWFXMKYSA-N ergosterol Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H](CC[C@]3([C@H]([C@H](C)/C=C/[C@@H](C)C(C)C)CC[C@H]33)C)C3=CC=C21 DNVPQKQSNYMLRS-SOWFXMKYSA-N 0.000 claims 1
- 150000002170 ethers Chemical class 0.000 claims 1
- 239000012595 freezing medium Substances 0.000 claims 1
- 239000011261 inert gas Substances 0.000 claims 1
- 150000004694 iodide salts Chemical class 0.000 claims 1
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 claims 1
- 150000002596 lactones Chemical class 0.000 claims 1
- CAHGCLMLTWQZNJ-RGEKOYMOSA-N lanosterol Chemical compound C([C@]12C)C[C@@H](O)C(C)(C)[C@H]1CCC1=C2CC[C@]2(C)[C@H]([C@H](CCC=C(C)C)C)CC[C@@]21C CAHGCLMLTWQZNJ-RGEKOYMOSA-N 0.000 claims 1
- 229940058690 lanosterol Drugs 0.000 claims 1
- 239000002502 liposome Substances 0.000 claims 1
- 239000006194 liquid suspension Substances 0.000 claims 1
- 229910052757 nitrogen Inorganic materials 0.000 claims 1
- 239000002736 nonionic surfactant Substances 0.000 claims 1
- 150000002482 oligosaccharides Polymers 0.000 claims 1
- 239000001301 oxygen Substances 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 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 1
- 150000008104 phosphatidylethanolamines Chemical class 0.000 claims 1
- 150000003905 phosphatidylinositols Chemical class 0.000 claims 1
- 229920000747 poly(lactic acid) Polymers 0.000 claims 1
- 229920002463 poly(p-dioxanone) polymer Polymers 0.000 claims 1
- 229920002627 poly(phosphazenes) Polymers 0.000 claims 1
- 229920000058 polyacrylate Polymers 0.000 claims 1
- 229920002239 polyacrylonitrile Polymers 0.000 claims 1
- 229920001515 polyalkylene glycol Polymers 0.000 claims 1
- 108010064470 polyaspartate Proteins 0.000 claims 1
- 239000000622 polydioxanone Substances 0.000 claims 1
- 229920000728 polyester Polymers 0.000 claims 1
- 229920002643 polyglutamic acid Polymers 0.000 claims 1
- 229920000098 polyolefin Polymers 0.000 claims 1
- 229920001184 polypeptide Polymers 0.000 claims 1
- 229920001451 polypropylene glycol Polymers 0.000 claims 1
- 229920001282 polysaccharide Polymers 0.000 claims 1
- 239000005017 polysaccharide Substances 0.000 claims 1
- 150000004804 polysaccharides Polymers 0.000 claims 1
- 229920002635 polyurethane Polymers 0.000 claims 1
- 239000004814 polyurethane Substances 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 claims 1
- 102000004196 processed proteins & peptides Human genes 0.000 claims 1
- 235000010388 propyl gallate Nutrition 0.000 claims 1
- 239000000473 propyl gallate Substances 0.000 claims 1
- 229940075579 propyl gallate Drugs 0.000 claims 1
- 229920006395 saturated elastomer Polymers 0.000 claims 1
- 239000000600 sorbitol Substances 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 239000000758 substrate Substances 0.000 claims 1
- 239000002562 thickening agent Substances 0.000 claims 1
- 235000010384 tocopherol Nutrition 0.000 claims 1
- 229960001295 tocopherol Drugs 0.000 claims 1
- 229930003799 tocopherol Natural products 0.000 claims 1
- 239000011732 tocopherol Substances 0.000 claims 1
- 238000002604 ultrasonography Methods 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
- 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 claims 1
- 238000003384 imaging method Methods 0.000 abstract 1
- 238000010586 diagram Methods 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Radiology & Medical Imaging (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Acoustics & Sound (AREA)
- Physics & Mathematics (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
- Degasification And Air Bubble Elimination (AREA)
- Investigating Or Analyzing Materials By The Use Of Ultrasonic Waves (AREA)
- Freezing, Cooling And Drying Of Foods (AREA)
- Ultra Sonic Daignosis Equipment (AREA)
- Physical Or Chemical Processes And Apparatus (AREA)
- Manufacturing Of Micro-Capsules (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Treating Waste Gases (AREA)
- Sampling And Sample Adjustment (AREA)
Abstract
담체 액체가 생리적으로 허용가능한 것인 유용한 첨가제 및 안정제를 함유하는 냉동 수성 담체 액체내에 고정된 미세 가스 기포의 현탁물이 개시되어 있는데, 고정된 미세 가스 기포는 소실성의 외피 또는 실체적인 막에 의하여 결합된 미세 기포이다. 본 발명의 현탁물은 액체 형태로 존재할 때 주사가능하며 생체의 혈액풀 및 조직의 초음파 화상 진단에 있어서 조영제로서 유용하다. 미세 가스 기포는 평균 크기가 50㎛ 이하, 바람직하게는 10㎛ 이하, 보다 바람직하게는 2㎛ 내지 8㎛인 미세 기포의 현탁물을 -1˚C 내지 -76˚C의 온도로 냉동시키고, 이 온도를 장시간 동안 유지시킴으로서 담체 중에 고정된다. 이 미세기포는 박판 인지질과 같은 계면 활성제에 의하여 안정화될 수 있거나, 합성 또는 천연 중합체 또는 단백질로 이루어진 막을 함유할 수 있다. 미세 기포 현탁물의 냉장 방법 및 그의 용도가 또한 개시되어 있다.
Description
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도는 저장온도에 따라 수성 담체 매질 중의 SF6및 C5F12미세 기포 5%를 함유한 공기의 해동 현탁물중의 기포는 농도(수) 변화의 플룻도, 제2도는 저장 온도에 따른 수성 담체 매질 중의 SF6및 C5F12미세 기포 5%를 함유한 공기의 해동 현탁물의 전체 가스 부피의 변화의 플룻도, 제3도는 적용된 외부 압력과 저장 온도에 따른 해동된 미해 기포 현탁물의 흡광도의 변화를 나타낸 그래프도, 제4도는 서로 다른 온도에서 저장한 후에 해동 현탁물에 적용된 외부 압력에 따른 상대 흡광도의 변화를 나타낸 다이어그램도, 제5도는 3㎛, 4㎛ 및 6㎛의 평균 크기의 구경 측정이 가능한 미세 기포의 수(제5a도) 및 가스 부피(제5b도)면에서의 미세 기포의 크기 분포를 나타낸 다이어그램도.
Claims (25)
- 가스 기포 및 유용한 첨가제를 함유하는 담체 매질이 생리적으로 허용가능한 담체이고, 고정된 가스기포가 소실성의 외피 또는 실체적인 막에 의하여 경계지워진 미세 기포이고, 액체 형태로 존재할 때 주사 가능하며 생체의 혈액풀 및 조직의 초음파 화상 진단에 있어서 조영제로서 유용한 것을 특징으로 하는 냉동 수성 담체 매질 내에 고정된 가스 기포의 냉동 현탁물.
- 제1항에 있어서, 냉동 매질의 온도가 -1˚C 내지 -196˚C, 바람직하게는 -10˚C 내지 -76˚C인 현탁물.
- 제1항 또는 제2항에 있어서, 대부분의 미세 기포의 크기가 50㎛ 이하, 바람직하게는 10㎛이하인 현탁물.
- 제3항에 있어서, 미세 기포의 크기가 2㎛ 내지 9㎛, 바람직하게 3㎛ 내지 5㎛인 현탁물.
- 제1항 또는 제2항에 있어서, 첨가제가 계면활성제로서 단일 또는 복수개의 분자 막층 형태의 박막 인지질을 포함하는 현탁물.
- 제5항에 있어서, 박막 인지질이 단일막 또는 다층막 리포좀의 형태인 현탁물.
- 제5항에 있어서, 박막 인지질이 포화 인지질인 현탁물.
- 제6항 또는 제7항에 있어서, 인지질이 포스파티드산, 포스파티딜콜린, 포스파티딜에탄올아민, 포스파티딜세린, 포스파티딜글리세롤, 포스파티딜이노시톨, 카지올리핀, 및 스핑고미엘린 또는 그의 혼합물로부터 선택된 것인 현탁물.
- 제1항 또는 제2항에 있어서, 첨가제가 디세틸포스페이트, 콜레스테롤, 에르고스테롤, 피토스테롤, 라노스테롤, 토코페롤, 프로필 갈레이트, 아스코르빌 팔미테이트 및 부틸화 히드록시톨루엔으로부터 선택된 물질을 포함하는 현탁물.
- 제1항 또는 제2항에 있어서, 첨가제가 소르비톨, 또는 폴리옥시에틸렌, 폴리옥시프로필렌 공중합체와 같은 비이온계 계면 활성제를 포함하는 현탁물.
- 제1항 내지 제10항 중 어느 하나의 항에 있어서, 첨가제가 선형 및 가교 결합 폴리- 및 올리고-사카라이드, 당, 친수성, 중합체 및 요오드화 화합물로부터 선택된 증점제 및(또는) 안정제를 함유된 계면 활성제에 대하여 약 1 : 5 내지 100 : 1의 중량비로 포함하는 현탁물.
- 제1항 내지 제11항 중 어느 하나의 항에 있어서, 첨가제가 지방산, 지방산 및 알코올의 폴리올과의 에스테르 및 에테르로부터 선택된 비박층상의 계면 활성제를 50중량%이하로 더 함유하는 현탁물.
- 제12항에 있어서, 폴리올이 폴리알킬렌 글리콜, 폴리알킬렌화 당 및 다른 탄수화물, 및 폴리알킬렌화 글리세롤인 현탁물.
- 제1항 또는 제2항에 있어서, ㎖당 107∼108개의 미세 기포, ㎖당 108~10|9개의 미세 기포, 또는 ㎖당 109∼1010개의 미세 기포를 함유하는 현탁물.
- 제1항 또는 제2항에 있어서, 막이 합성 또는 천연 중합체 또는 단백질로 이루어진 것인 현탁물.
- 제15항에 있어서, 중합체가 다당류, 폴리아미노산 및 그의 에스테르, 폴리락티드 및 폴리글리콜리드 및 그의 공중합체, 락티드와 락톤의 공중합체, 폴리펩티드, 폴리-(오르토)에스테르, 폴리디옥사논, 폴리-β-아미노케톤, 폴리포스파젠, 폴리안하이드라이드, 폴리알킬-(시아노)-아크릴레이트, 폴리올레핀, 폴리아크릴레이트, 폴리아크릴로니트릴, 비가수분해성 폴리에스테르, 폴리우레탄 및 폴리우레아, 폴리글루탐산 또는 폴리아스파르트산 유도체 및 그와 다른 아미노산과의 공중합체로부터 선택된 것인 현탁물.
- 제15항에 있어서, 단백질이 알부민인 현탁물.
- 제1항에 있어서, 가스가 할로겐 함유 가스, 공기, 산소, 질소, 이산화탄소 또는 그의 혼합물로부터 선택된 것인 현탁물.
- 제18항에 있어서, 할로겐 함유 가스가 SF6, CF4, C2F6, C2F8, C3F6, C3F8, C4F6, C4F8, C4F10, C5F10, C5F|12및 그의 혼합물로 이루어진 군으로부터 선택된 것인 현탁물.
- a) 액체 현탁물을 냉각 장치 중에 놓는 단계, b) 현탁물의 응결점 이하의 온도로, 바람직하게는 -1˚C 내지 -196˚C , 보다 바람직하게는 -10˚C 내지 -76˚C 로 냉각함으로써 미세 기포를 고정시키는 단계, 및 c) 냉동조건을 장시간동안 유지시키는 단계를 포함하는 것을 특징으로 하는 제1항 내지 제19항 중 어느 하나의 항에 따른 미세 기포 현탁물의 저장 방법.
- 제20항에 있어서, 냉동 현탁물을 불활성 가스, 또는 그 중에서 적어도 어느 하나는 미세 기포에 봉입된 가스인 가스들의 혼합물의 대기 하에 유지시키는 방법.
- 제20항에 있어서, 미세 기포가 가스 또는 그 중에서 적어도 어느 하나는 비점이 -18˚C 인 가스들의 혼합물을 포함하는 방법.
- 제20항에 있어서, 사용 전에 현탁물을 해동시켜서 장시간 동안 실온에서 유지시키는 방법.
- 기판 또는 조직의 초음파 화상 진단에 사용되기 위한 제1항 내지 제19항 중어느 하나의 항에 따른 주사 가능한 현탁물의 용도.
- 초음파 검사용 조영제를 제조하기 위한 제1항 내지 제19항 중 어느 하나의 항에 따른 주사 가능한 현탁물의 용도.※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
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GB9106686D0 (en) * | 1991-03-28 | 1991-05-15 | Hafslund Nycomed As | Improvements in or relating to contrast agents |
GB9107628D0 (en) * | 1991-04-10 | 1991-05-29 | Moonbrook Limited | Preparation of diagnostic agents |
ATE191346T1 (de) † | 1991-09-17 | 2000-04-15 | Sonus Pharma Inc | Gasförmige ultraschallkontrastmittel |
IL104084A (en) † | 1992-01-24 | 1996-09-12 | Bracco Int Bv | Sustainable aqueous suspensions of pressure-resistant and gas-filled blisters, their preparation, and contrast agents containing them |
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1995
- 1995-12-11 IL IL11632895A patent/IL116328A/xx not_active IP Right Cessation
- 1995-12-14 CZ CZ19962420A patent/CZ291540B6/cs not_active IP Right Cessation
- 1995-12-14 DE DE69522670T patent/DE69522670T3/de not_active Expired - Lifetime
- 1995-12-14 AT AT95937158T patent/ATE205404T1/de active
- 1995-12-14 AU AU39352/95A patent/AU701807B2/en not_active Ceased
- 1995-12-14 NZ NZ295744A patent/NZ295744A/xx unknown
- 1995-12-14 CN CN95191640A patent/CN1066965C/zh not_active Expired - Fee Related
- 1995-12-14 CA CA002181340A patent/CA2181340C/en not_active Expired - Fee Related
- 1995-12-14 EP EP95937158A patent/EP0744962B2/en not_active Expired - Lifetime
- 1995-12-14 DK DK95937158T patent/DK0744962T4/da active
- 1995-12-14 JP JP51854396A patent/JP3958358B2/ja not_active Expired - Fee Related
- 1995-12-14 WO PCT/IB1995/001124 patent/WO1996018420A1/en active IP Right Grant
- 1995-12-14 KR KR1019960704432A patent/KR100382811B1/ko not_active IP Right Cessation
- 1995-12-14 ES ES95937158T patent/ES2162943T5/es not_active Expired - Lifetime
- 1995-12-14 PT PT95937158T patent/PT744962E/pt unknown
- 1995-12-15 ZA ZA9510721A patent/ZA9510721B/xx unknown
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1996
- 1996-08-09 NO NO19963327A patent/NO313031B1/no not_active IP Right Cessation
- 1996-08-15 FI FI963202A patent/FI120722B/fi not_active IP Right Cessation
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1997
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- 1997-08-12 US US08/909,099 patent/US5827504A/en not_active Expired - Lifetime
- 1997-10-06 US US08/944,408 patent/US5961956A/en not_active Expired - Lifetime
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