KR930000131A - 생물학적으로 활성 단백질, 펩티드 또는 폴리펩티드를 함유하는 이식재 조성물 및 그의 제조방법 - Google Patents
생물학적으로 활성 단백질, 펩티드 또는 폴리펩티드를 함유하는 이식재 조성물 및 그의 제조방법 Download PDFInfo
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- KR930000131A KR930000131A KR1019920010911A KR920010911A KR930000131A KR 930000131 A KR930000131 A KR 930000131A KR 1019920010911 A KR1019920010911 A KR 1019920010911A KR 920010911 A KR920010911 A KR 920010911A KR 930000131 A KR930000131 A KR 930000131A
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- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract 21
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract 15
- 229920001184 polypeptide Polymers 0.000 title claims abstract 11
- 102000004169 proteins and genes Human genes 0.000 title claims abstract 11
- 108090000623 proteins and genes Proteins 0.000 title claims abstract 11
- 238000000034 method Methods 0.000 title claims abstract 6
- 239000007943 implant Substances 0.000 title abstract 2
- 239000000203 mixture Substances 0.000 claims abstract 19
- 241001465754 Metazoa Species 0.000 claims abstract 3
- 238000007911 parenteral administration Methods 0.000 claims abstract 3
- 230000036765 blood level Effects 0.000 claims abstract 2
- 239000000843 powder Substances 0.000 claims 7
- 239000011248 coating agent Substances 0.000 claims 4
- 238000000576 coating method Methods 0.000 claims 4
- 239000000463 material Substances 0.000 claims 3
- 150000003839 salts Chemical class 0.000 claims 3
- 102000018997 Growth Hormone Human genes 0.000 claims 2
- 108010051696 Growth Hormone Proteins 0.000 claims 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims 2
- 241000282898 Sus scrofa Species 0.000 claims 2
- 229940061607 dibasic sodium phosphate Drugs 0.000 claims 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims 2
- 239000008240 homogeneous mixture Substances 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 229940045641 monobasic sodium phosphate Drugs 0.000 claims 2
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims 2
- 235000019799 monosodium phosphate Nutrition 0.000 claims 2
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims 2
- 239000007921 spray Substances 0.000 claims 2
- DUXYWXYOBMKGIN-UHFFFAOYSA-N trimyristin Chemical compound CCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCC DUXYWXYOBMKGIN-UHFFFAOYSA-N 0.000 claims 2
- PVNIQBQSYATKKL-UHFFFAOYSA-N tripalmitin Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCC PVNIQBQSYATKKL-UHFFFAOYSA-N 0.000 claims 2
- DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 claims 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims 1
- 241000271566 Aves Species 0.000 claims 1
- OMPIYDSYGYKWSG-UHFFFAOYSA-N Citronensaeure-alpha-aethylester Natural products CCOC(=O)CC(O)(C(O)=O)CC(O)=O OMPIYDSYGYKWSG-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
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 claims 1
- 241000283086 Equidae Species 0.000 claims 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims 1
- 108091092889 HOTTIP Proteins 0.000 claims 1
- 101000664737 Homo sapiens Somatotropin Proteins 0.000 claims 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims 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 claims 1
- 229930195725 Mannitol Natural products 0.000 claims 1
- 241001494479 Pecora Species 0.000 claims 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims 1
- MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 claims 1
- 102000013275 Somatomedins Human genes 0.000 claims 1
- 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 claims 1
- 229930006000 Sucrose Natural products 0.000 claims 1
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 claims 1
- MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 claims 1
- 229910021538 borax Inorganic materials 0.000 claims 1
- 238000001816 cooling Methods 0.000 claims 1
- 229920001577 copolymer Polymers 0.000 claims 1
- 229940057975 ethyl citrate Drugs 0.000 claims 1
- 230000003031 feeding effect Effects 0.000 claims 1
- 239000008103 glucose Substances 0.000 claims 1
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims 1
- 239000008101 lactose Substances 0.000 claims 1
- 235000020997 lean meat Nutrition 0.000 claims 1
- 239000000594 mannitol Substances 0.000 claims 1
- 235000010355 mannitol Nutrition 0.000 claims 1
- 235000013336 milk Nutrition 0.000 claims 1
- 239000008267 milk Substances 0.000 claims 1
- 210000004080 milk Anatomy 0.000 claims 1
- 238000003801 milling Methods 0.000 claims 1
- 238000002156 mixing Methods 0.000 claims 1
- 239000011574 phosphorus Substances 0.000 claims 1
- 229910052698 phosphorus Inorganic materials 0.000 claims 1
- 238000004080 punching Methods 0.000 claims 1
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose 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[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 claims 1
- 229920006395 saturated elastomer Polymers 0.000 claims 1
- 229960004599 sodium borate Drugs 0.000 claims 1
- 229910000029 sodium carbonate Inorganic materials 0.000 claims 1
- 229940001593 sodium carbonate Drugs 0.000 claims 1
- 235000017550 sodium carbonate Nutrition 0.000 claims 1
- 235000010339 sodium tetraborate Nutrition 0.000 claims 1
- 239000000600 sorbitol Substances 0.000 claims 1
- 238000001694 spray drying Methods 0.000 claims 1
- 239000003381 stabilizer Substances 0.000 claims 1
- 239000005720 sucrose Substances 0.000 claims 1
- 239000004094 surface-active agent Substances 0.000 claims 1
- 239000000454 talc Substances 0.000 claims 1
- 229910052623 talc Inorganic materials 0.000 claims 1
- 235000013769 triethyl citrate Nutrition 0.000 claims 1
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
Classifications
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- 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
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/07—Stiffening bandages
- A61L15/10—Stiffening bandages containing organic materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/27—Growth hormone [GH], i.e. somatotropin
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Endocrinology (AREA)
- Medicinal Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Zoology (AREA)
- Materials Engineering (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Materials For Medical Uses (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Prostheses (AREA)
Abstract
내용 없음
Description
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
Claims (12)
- 중량 기준으로, 약 20%-80%의 생물학적으로 활성인 단백질, 펩티드 또는 폴리펩티드, 약 10%-75%의 지방 또는 납 또는 그의 혼합물, 0%-약 20%의 완충재 또는 염 또는 그의 혼합물 및 0%-약 25%의 당을 각각 함유하 는 1-3층을 함유하는 밀집되고 함요(陷凹)되고 부분적으로 코우팅된 조성물을 특징으로 하는, 장시간에 걸쳐 본질적으로 동일하고 계속적인 양의 생물학적으로 활성인 단백질, 폘티드 또는 폴리펩티드의 비경구적 투여를 위한 이식가능한 조성물.
- 제1항에 있어서, 생물학적으로 활성인 단백질, 펩티드 또는 폴리펩티드가 돼지, 양, 말, 조류, 및 인간의 소마토트로핀을 포함하는 소마토트로핀, 소마토메딘, 및 성장 요소로 구성되는 군으로 부터 선택되고; 지방이 글리세릴 트리미리스테이트, 글리세릴 트리팔미테이트 및 글리세릴 트리스테아레이트로 구성되는 군으로 부터 선택되고, 완충제는 붕산나트륨, 탄산나트륨, 단염기 인산나트륨, 이염기 인산나트륨 및 그의 혼합물로 구성되는군으로 부터 선택되고, 당은 글루코즈, 만노즈, 수크로즈, 라피노즈, 소르비톨, 만니톨 및 락토즈로 구성되는군으로 부터 선택되고; 코우팅이 1또는 2층의 반투성 물질을 포함하고 임의로 안정화제, 계면활성제 또는 그의혼합물인 것으로 특징으로 하는 조성물.
- 제2항에 있어서, 돼지의 소마토트로핀이 E34 rpST, I122L+E34 rpST 및 A6TS11R+E34 rpST로 구성되는군으로 부터 선택되는 조성물.
- 제2함에 있어서, 완충제가 단염기 인산나트륨 및 이염기 인산나트륨의 혼합물인 조성물.
- 제2항에 있어서, 반투성 물질이, 중량 기준으로 약 1%-20%에틸시트레이트 또는 탈크를 함유하는 메타크릴 레이트 에스테르 공중 합체이고, 각 코우팅의 두께가 약 0.5밀-25밀인 조성물.
- 제1항에 있어서, 각층에 존재하는 생물학적으로 활성인 단백질, 펩티드 또는 폴리펩티드의 양이 함요로 부터 떨어져서 증가하는 조성물.
- 제1항에 의해 특징지워지는 바와 같은 이식가능한 조성물을 동물에 비경구적으로 투여하는 것을 특징으로하는, 생물학적으로 활성인 단백질, 펩티드 또는 폴리펩티드의 증가된 혈액 수준을 증가시키고, 유지시키고, 성장속도를 증가시키고, 공급효과틀 개선시키고, 살코기대 지방비를 개선시키고 수유동물에서 우유 생산을 증가시키는 방법.
- 제7항에 있어서, 이식가능한 조성물이 제2항에 의해 특징지워지는 바와 같은 방법.
- (a)생물학적으로 활성인 단백질, 폡티드 또는 폴리펩티드를 용융된 지방, 납 또는 그의 혼합물과 및 임의로 완충제, 염 또는 당과 혼합하여 굵은 분말을 형성하는 단계; (b)1-3층의 굵은 분말을 밀집시켜 밀집된 덩어리를 형성하는 단계; (c)밀집된 덩어리를 끝이 뾰족한 돌출부로 펀칭해서 밀집된 덥어리를 끝이 뾰족한 함요를 형성하는 단계; 및 (d)코우팅을 통해 밀집된 덩어리로부터의 함요에 의해 통로가 형성되도록 반투성 물질로 함요되고 밀집된 덩어리를 코우팅하는 단계, 를 특징으로 하는 장시간에 걸쳐 본질적으로 동일하고 계속적인 양의 생물학적으로 활성인 단백질, 펩티드 또는 폴리펩티드의 비경구적 투여를 위한 이식가능한 조성물의 제조방법.
- 제9항에 있어서, 단계(b)및 단계(c)가 동시에 일어나는 방법.
- 제9항에 있어서, 밀집된 덩어리가 제1항의 조성물에 의해 특징지워지는 방법.
- 제9항에 있어서, 단계(a)가: (a)생물학적으로 활성인 단백질, 펩티드 또는 폴리펩티드 및 완충제 또는 염 또는 그의 혼합물을 물에 용해시켜 용액을 형성하는 단계; (b)용액을 분무 건조시켜 분무 건조된 분말을 형성하는 단계; (c)분무 건조된 분말을 용융된 지방, 납 또는 그의 혼합물에 용해시켜 균질의 혼합물을 형성하는 단계 ;(d)균질의 혼합물을 냉각시켜 분말을 형성하는 단계; (e)분말을 압축시켜 압축된 덩어리를 형성하는 단계; 및 (f)압축된 덩어리를 제분시켜 굵은 과립상 분말을 형성하는 단계를 특징으로 하는 방법.※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US71989891A | 1991-06-24 | 1991-06-24 | |
| US7/719898 | 1991-06-24 | ||
| US07/719898 | 1991-06-24 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR930000131A true KR930000131A (ko) | 1993-01-15 |
| KR100221031B1 KR100221031B1 (ko) | 1999-09-15 |
Family
ID=24891827
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019920010911A KR100221031B1 (ko) | 1991-06-24 | 1992-06-23 | 생물학적으로 활성 단백질, 펩티드 또는 폴리펩티드를 함유하는 이식재 조성물 및 그의 제조 방법 |
Country Status (24)
| Country | Link |
|---|---|
| EP (1) | EP0523330B1 (ko) |
| JP (1) | JP3597205B2 (ko) |
| KR (1) | KR100221031B1 (ko) |
| CN (1) | CN1050301C (ko) |
| AT (1) | ATE135565T1 (ko) |
| AU (1) | AU656200B2 (ko) |
| BR (1) | BR9202374A (ko) |
| CA (1) | CA2071757C (ko) |
| DE (1) | DE69209173T2 (ko) |
| DK (1) | DK0523330T3 (ko) |
| ES (1) | ES2087337T3 (ko) |
| GE (1) | GEP19970992B (ko) |
| GR (1) | GR3019457T3 (ko) |
| HU (1) | HU217547B (ko) |
| IE (1) | IE74398B1 (ko) |
| IL (1) | IL102287A (ko) |
| LV (1) | LV11816B (ko) |
| MD (1) | MD1394G2 (ko) |
| MX (1) | MX9203175A (ko) |
| RU (1) | RU2080119C1 (ko) |
| SG (1) | SG47955A1 (ko) |
| TW (1) | TW215058B (ko) |
| UA (1) | UA26137C2 (ko) |
| ZA (1) | ZA924613B (ko) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5736152A (en) * | 1995-10-27 | 1998-04-07 | Atrix Laboratories, Inc. | Non-polymeric sustained release delivery system |
| BR9912275A (pt) | 1998-07-20 | 2001-04-17 | Peptech Ltd | Formulação de bioimplante |
| US8052982B2 (en) | 1998-07-20 | 2011-11-08 | Peptech Animal Health Pty Limited | Bioimplant formulation comprising lecithin and stearin |
| JP2001058955A (ja) * | 1999-06-17 | 2001-03-06 | Inst Of Physical & Chemical Res | 生理活性ペプチド徐放性製剤 |
| KR20090007504A (ko) | 2000-02-24 | 2009-01-16 | 몬산토 테크놀로지 엘엘씨 | 소마토트로핀의 지속적인 방출을 위한 비수성 주사제제들 |
| WO2002000261A2 (en) | 2000-06-26 | 2002-01-03 | Monsanto Technology Llc | Surfactant-containing formulations for extended release of somatotropin |
| US6664234B1 (en) | 2000-06-30 | 2003-12-16 | Monsanto Technology Llc | Non-aqueous injectable formulation preparation with pH adjusted for extended release of somatotropin |
| JP4931282B2 (ja) * | 2000-10-02 | 2012-05-16 | 日本ケミカルリサーチ株式会社 | 生理活性ペプチド含有粉末 |
| DE10161078A1 (de) * | 2001-12-12 | 2003-08-28 | Achim Goepferich | Matrizes zur Stabilisierung und kontrollierten Freisetzung von Problemarzneistoffen |
| JP2005145821A (ja) * | 2003-11-11 | 2005-06-09 | Kao Corp | 打錠製剤 |
| CN102753573A (zh) | 2009-12-21 | 2012-10-24 | Ambrx公司 | 经过修饰的牛促生长素多肽和其用途 |
| NZ600363A (en) | 2009-12-21 | 2014-07-25 | Ambrx Inc | Modified porcine somatotropin polypeptides and their uses |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4271113A (en) * | 1978-04-17 | 1981-06-02 | Alza Corporation | Process for forming a passageway in an osmotic device |
| CA1257199A (en) * | 1986-05-20 | 1989-07-11 | Paul Y. Wang | Preparation containing bioactive macromolecular substance for multi-months release in vivo |
| US4863736A (en) * | 1987-03-16 | 1989-09-05 | Monsanto Company | Somatotropin prolonged release |
| US4795644A (en) * | 1987-08-03 | 1989-01-03 | Merck & Co., Inc. | Device for pH independent release of drugs through the Donnan-like influence of charged insoluble resins |
| HUT69680A (en) * | 1990-08-09 | 1995-09-28 | Endocon Inc | Implant and apparatus for delivering multiple drug and process for production of theese |
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1992
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