FI114898B - Förfarande för framställning av joniska molekylkonjugater av bionedbrytbara polyestrar och bioaktiva polypeptider - Google Patents
Förfarande för framställning av joniska molekylkonjugater av bionedbrytbara polyestrar och bioaktiva polypeptider Download PDFInfo
- Publication number
- FI114898B FI114898B FI953314A FI953314A FI114898B FI 114898 B FI114898 B FI 114898B FI 953314 A FI953314 A FI 953314A FI 953314 A FI953314 A FI 953314A FI 114898 B FI114898 B FI 114898B
- Authority
- FI
- Finland
- Prior art keywords
- polyester
- acid
- polypeptide
- lactide
- ionic
- Prior art date
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/23—Luteinising hormone-releasing hormone [LHRH]; Related peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/593—Polyesters, e.g. PLGA or polylactide-co-glycolide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/02—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/655—Somatostatins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Endocrinology (AREA)
- Biochemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Gastroenterology & Hepatology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Polyesters Or Polycarbonates (AREA)
- Medicinal Preparation (AREA)
- Biological Depolymerization Polymers (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Claims (23)
1. Metod att syntetisera en komposition, kanne-tecknad av (a) att tillhandahälla en polyester och en 5 bioaktiv polypeptid som har minst en effektiv jonogen amin och (b) att joniskt konjugera nämnda polyester till nämnda polypeptid för att bilda ett jonmolekylärt konjugat i vil-ket polypeptiden är joniskt konjugerad till polyestern.
2. Metod enligt patentkrav 1, kännetecknad av 10 att minst 50 viktprocent av den i kompositionen närvarande polypeptiden är joniskt konjugerad till polyestern.
3. Metod enligt patentkrav 2, kännetecknad av att nämnda polyestrar innehar syraavslutade hydroxyl änd-grupper.
4. Metod enligt patentkrav 3, kännetecknad av att nämnda hydroxyländgrupper delvis är syraavslutade med glutarsyraanhydrid.
5. Metod enligt patentkrav 3, kännetecknad av att nämnda hydroxyländgrupper är helt syraavslutade med 20 glutarsyraanhydrid.
6. Metod enligt patentkrav 2, kännetecknad av att nämnda polyestrar syntetiseras med användning av hyd- • roxipolykarboxylsyrakedj einitiatorer.
/ 7. Metod enligt patentkrav 2, kännetecknad av : 25 att hydroxyländgrupper av nämnda polyestrar är syraavslu- : : tade. :‘t;
8. Metod enligt patentkrav 7, kännetecknad av att nämnda hydroxyländgrupper är delvis syraavslutade med glutarsyraanhydrid.
9. Metod enligt patentkrav 7, kännetecknad av att nämnda hydroxyländgrupper är helt syraavslutade med ‘•’M glutarsyraanhydrid.
10. Metod enligt patentkrav 2, kännetecknad av >, ; att syntes av nämnda polyester resulterar i en genomsnitt- ' ! 35 lig polymeriseringsgrad mellan 10 och 300. 114898
11. Metod enligt patentkrav 10, kännetecknad av att nämnda polyester har en karboxyl- till hydroxyl-ändgruppskvot större än ett.
12. Metod enligt patentkrav 2, kännetecknad av 5 att nämnda polyester/polypeptidjonmolekylära konjugat syn- tetiseras sa att: (a) polyestern upplöses i tetrahydrofvi ran, aceton, eller etylenglykoldimetyleter varefter en bas tillsätts; och (b) en vattenhaltig lösning av en polypep-tid eller polypeptidsalt vid polypeptid/polyesterfyll- 10 niväer om 2 % tili 50 % vikt/vikt (polypeptid/polyester) tillsätts.
13. Metod enligt patentkrav 12, kännetecknad av att nämnda polypeptid är ett sait av en syra med ett pKa store än eller lika med 3,5.
14. Metod enligt patentkrav 12, kännetecknad av att nämnda polypeptid innefattar 1 till 50 procent av den totala vikten för nämnda joniska konjugat.
15. Metod enligt patentkrav 12, kännetecknad av att mer än 85 % av nämnda polypeptid närvarande i 20 nämnda komposition är joniskt konjugerad tili nämnda polyester .
16. Metod enligt patentkrav 12, kännetecknad av att nämnda reaktion resulterar i bildandet av en jon- ' .* bindning mellan nämnda reaktanter.
17. Metod enligt patentkrav 1, kännetecknad av att nämnda polyester innefattar en eller flera fria C00H- > * I r. grupper joniskt konjugerade tili polypeptiden.
18. Metod enligt patentkrav 1, kännetecknad av att nämnda polyester är sammansatt av en medlen vald frän ‘il! 30 gruppen innefattande L-mjölksyra; D-mjölksyra; DL-mjölk-syra; e-kaprolakton; p-dioxanon; e-kapronsyra; alkylenoxa-t : lat; cykloalkylenoxalat; alkylensuccinat; /3-hydroxibuty- :*'· rat; substituerad eller osubstituerad trimetylenkarbonat; /. 1,5-dioxepan-2-on; 1,4-dioxepan-2-on; glykolid, glykolsra; ! 35 L-laktid; D-laktid; DL-laktid; mesolaktid; och godtyckliga optiskt aktiva isomerer; racemat eller sampolymerer därav. 114898
19. Metod enligt patentkrav 1, kännetecknad av att nämnda polyester har en viskositet pa mellan cirka O, 05 till cirka 0,7 dl/g i kloroformn och en genomsnittlig molekylvikt pä cirka 1 200 till 40 000.
20. Metod enligt patentkrav 1, kännetecknad av att nämnda polypeptid valts frän gruppen bestäende av LHRH, somatostatin, bombesin/GRP, kalcitonin, bradykinin, galanin, MSH, GRF, amylin, takykininer, sekretin, PTH, CGRP, neuromediner, PTHrp, glukagon, neurotensin, ACTH, 10 GHRP, GLP, VIP, PACAP, enkafelin, PYY, motilin, substans P, NPY, TSH och analoger och fragment därav.
21. Metod enligt patentkrav 1, kännetecknad av att nämnda joniska konjugat förmär frigöra en terapeutiskt effektiv dos av nämnda polypeptid i minst sju dagar.
22. Metod att syntetisera en mikropartikel kän netecknad av att (a) en komposition syntetiserad enligt patentkrav 1 upplöses i ett aprotiskt, med vatten blandbart organiskt lösningsmedel; (b) nämnda organiska lösningsmedel blandas i vatten; och (c) nämnda mikropar-20 tiklar isoleras ur nämnda vatten.
23. Metod enligt patentkrav 22, kännetecknad av att nämnda organiska lösningsmedel väljs frän en grupp * bestäende av aceton, acetonitril, tetrahydrofuran, dime- tylformamid, och dimetoxietylenglykol. » » » ·
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IE930005 | 1993-01-06 | ||
| IE930005 | 1993-01-06 | ||
| US9400148 | 1994-01-05 | ||
| PCT/US1994/000148 WO1994015587A2 (en) | 1993-01-06 | 1994-01-05 | Ionic molecular conjugates of biodegradable polyesters and bioactive polypeptides |
| CNB941085236A CN1163260C (zh) | 1993-01-06 | 1994-07-20 | 可生物降解聚酯和生物活性多肽的离子性分子轭合物 |
| CN94108523 | 1994-07-20 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI953314A FI953314A (sv) | 1995-07-05 |
| FI953314A0 FI953314A0 (sv) | 1995-07-05 |
| FI114898B true FI114898B (sv) | 2005-01-31 |
Family
ID=37075859
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI953314A FI114898B (sv) | 1993-01-06 | 1995-07-05 | Förfarande för framställning av joniska molekylkonjugater av bionedbrytbara polyestrar och bioaktiva polypeptider |
Country Status (20)
| Country | Link |
|---|---|
| EP (1) | EP0678018B1 (sv) |
| JP (1) | JPH08505395A (sv) |
| CN (1) | CN1163260C (sv) |
| AT (1) | ATE236655T1 (sv) |
| AU (1) | AU680650B2 (sv) |
| CA (1) | CA2150574A1 (sv) |
| CZ (2) | CZ293378B6 (sv) |
| DE (1) | DE69432459T2 (sv) |
| DK (1) | DK0678018T3 (sv) |
| ES (1) | ES2196023T3 (sv) |
| FI (1) | FI114898B (sv) |
| HU (1) | HU220137B (sv) |
| NZ (1) | NZ261250A (sv) |
| PL (1) | PL174772B1 (sv) |
| PT (1) | PT678018E (sv) |
| RU (2) | RU2146128C1 (sv) |
| SG (1) | SG47043A1 (sv) |
| SK (1) | SK74495A3 (sv) |
| WO (1) | WO1994015587A2 (sv) |
| ZA (1) | ZA9477B (sv) |
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| TR201702016A2 (tr) | 2017-02-10 | 2018-08-27 | Tuerkiye Bilimsel Ve Teknolojik Arastirma Kurumu Tuebitak | Düşük mali̇yetli̇ yüksek moleküler ağirlikli ve yüksek çözünürlüğe sahi̇p poli̇gli̇koli̇k asi̇t sentezi̇ |
| KR20220140711A (ko) | 2020-01-13 | 2022-10-18 | 듀렉트 코퍼레이션 | 불순물이 감소된 지속 방출 약물 전달 시스템 및 관련 방법 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4356166A (en) * | 1978-12-08 | 1982-10-26 | University Of Utah | Time-release chemical delivery system |
| IE52535B1 (en) * | 1981-02-16 | 1987-12-09 | Ici Plc | Continuous release pharmaceutical compositions |
| US4609707A (en) * | 1983-11-10 | 1986-09-02 | Genetic Systems Corporation | Synthesis of polymers containing integral antibodies |
| US5071909A (en) * | 1989-07-26 | 1991-12-10 | Millipore Corporation | Immobilization of proteins and peptides on insoluble supports |
| US5162505A (en) * | 1989-09-19 | 1992-11-10 | Centocor | Proteins modified with positively charged carriers and compositions prepared therefrom |
| CA2046830C (en) * | 1990-07-19 | 1999-12-14 | Patrick P. Deluca | Drug delivery system involving inter-action between protein or polypeptide and hydrophobic biodegradable polymer |
| GB9310030D0 (en) * | 1993-05-15 | 1993-06-30 | Scras | Dry processed particles and process for the preparation of the same |
-
1994
- 1994-01-05 HU HU9502029A patent/HU220137B/hu not_active IP Right Cessation
- 1994-01-05 ES ES94906037T patent/ES2196023T3/es not_active Expired - Lifetime
- 1994-01-05 PL PL94309776A patent/PL174772B1/pl not_active IP Right Cessation
- 1994-01-05 CZ CZ19951734A patent/CZ293378B6/cs not_active IP Right Cessation
- 1994-01-05 RU RU95118395/14A patent/RU2146128C1/ru not_active IP Right Cessation
- 1994-01-05 PT PT94906037T patent/PT678018E/pt unknown
- 1994-01-05 EP EP94906037A patent/EP0678018B1/en not_active Expired - Lifetime
- 1994-01-05 AU AU59921/94A patent/AU680650B2/en not_active Ceased
- 1994-01-05 NZ NZ261250A patent/NZ261250A/xx unknown
- 1994-01-05 SG SG1996004005A patent/SG47043A1/en unknown
- 1994-01-05 DE DE69432459T patent/DE69432459T2/de not_active Expired - Fee Related
- 1994-01-05 SK SK744-95A patent/SK74495A3/sk unknown
- 1994-01-05 AT AT94906037T patent/ATE236655T1/de not_active IP Right Cessation
- 1994-01-05 CA CA002150574A patent/CA2150574A1/en not_active Abandoned
- 1994-01-05 CZ CZ20002050A patent/CZ293425B6/cs not_active IP Right Cessation
- 1994-01-05 RU RU99122608/04A patent/RU2185393C2/ru not_active IP Right Cessation
- 1994-01-05 JP JP6516182A patent/JPH08505395A/ja active Pending
- 1994-01-05 WO PCT/US1994/000148 patent/WO1994015587A2/en active IP Right Grant
- 1994-01-05 DK DK94906037T patent/DK0678018T3/da active
- 1994-01-06 ZA ZA9477A patent/ZA9477B/xx unknown
- 1994-07-20 CN CNB941085236A patent/CN1163260C/zh not_active Expired - Fee Related
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1995
- 1995-07-05 FI FI953314A patent/FI114898B/sv active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| DK0678018T3 (da) | 2003-04-28 |
| NZ261250A (en) | 1997-08-22 |
| ATE236655T1 (de) | 2003-04-15 |
| AU5992194A (en) | 1994-08-15 |
| HU9502029D0 (en) | 1995-09-28 |
| HUT73188A (en) | 1996-06-28 |
| RU2146128C1 (ru) | 2000-03-10 |
| HU220137B (hu) | 2001-11-28 |
| PL174772B1 (pl) | 1998-09-30 |
| SG47043A1 (en) | 1998-03-20 |
| PT678018E (pt) | 2003-08-29 |
| CZ173495A3 (en) | 1996-01-17 |
| CN1163260C (zh) | 2004-08-25 |
| JPH08505395A (ja) | 1996-06-11 |
| ES2196023T3 (es) | 2003-12-16 |
| SK74495A3 (en) | 1997-01-08 |
| DE69432459T2 (de) | 2003-11-27 |
| CA2150574A1 (en) | 1994-07-21 |
| ZA9477B (en) | 1994-08-11 |
| AU680650B2 (en) | 1997-08-07 |
| EP0678018A1 (en) | 1995-10-25 |
| FI953314A (sv) | 1995-07-05 |
| WO1994015587A3 (en) | 1994-09-01 |
| RU2185393C2 (ru) | 2002-07-20 |
| CN1115252A (zh) | 1996-01-24 |
| EP0678018A4 (en) | 1998-09-09 |
| CZ293378B6 (cs) | 2004-04-14 |
| CZ293425B6 (cs) | 2004-04-14 |
| DE69432459D1 (de) | 2003-05-15 |
| WO1994015587A2 (en) | 1994-07-21 |
| PL309776A1 (en) | 1995-11-13 |
| EP0678018B1 (en) | 2003-04-09 |
| FI953314A0 (sv) | 1995-07-05 |
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