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FI96919B - Veteen liukenemattomia polypeptidejä - Google Patents

Veteen liukenemattomia polypeptidejä Download PDF

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Publication number
FI96919B
FI96919B FI884297A FI884297A FI96919B FI 96919 B FI96919 B FI 96919B FI 884297 A FI884297 A FI 884297A FI 884297 A FI884297 A FI 884297A FI 96919 B FI96919 B FI 96919B
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Prior art keywords
water
salt
peptide
insoluble
pamoate
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FI884297A
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English (en)
Swedish (sv)
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FI96919C (fi
FI884297A0 (fi
FI884297A (fi
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Piero Orsolini
Rolland-Yves Mauvernay
Romano Deghenghi
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Debiopharm Sa
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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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/08—Peptides having 5 to 11 amino acids
    • A61K38/09—Luteinising hormone-releasing hormone [LHRH], i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
    • A61K9/1647—Polyesters, e.g. poly(lactide-co-glycolide)

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Biomedical Technology (AREA)
  • Reproductive Health (AREA)
  • Endocrinology (AREA)
  • Dermatology (AREA)
  • Neurosurgery (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)

Description

96919
VETEEN LIUKENEMATTOMIA POLYPEPTIDEJÄ I VATTEN OLÖSLIGA POLYPEPTIDER
Tämän keksinnön kohteena on patenttivaatimuksen 1 johdanto-osan mukainen menetelmä farmaseuttisesti hyväksyttävän koostumuksen valmistamiseksi. Keksintö koskee terapeuttisesti aktiivisten, mutta veteen liukenemattomien polypepti-dien farmaseuttisia koostumuksia, jotka aikaan saavat peptidien jatkuvan, kontrolloidun ja pitkittyneen vapautumisen fysiologis-tyyppisessä ympäristössä. Keksinnölle on edelleen luonteenomaista, että käytetään elimistössä hajoavia ja elimistöön soveltuvia polymeerejä ja kopolymeerejä alustana, johon veteen liukenemattomat polypeptidit dispergoi-daan tai kapseloidaan.
Tarve saada aikaan peptidien pitkittynyttä vapautumista parenteraalisessa antotavassa on tunnettu jo pitkään (vrt. T.M.S. Chang "Biodegradable semipermeable Microcapsule : " containing enzymes, hormones, vaccines and other biologi-V · cals" lehdessä J. Bioengineering 1, 25 (1976); R. Langer . '.j "Controlled Release of Macromolecules" lehdessä Chemtech, ·; helmikuu 1982, sivut 98-105; F.G. Hutchinson ja B.J.A. Furr • · « 4 "Biodegradable carriers for sustained release of polypepti- • · des" lehdessä TIBTECH, huhtikuu 1987 (voi. 5) sivut 102-106. Alan tunnettua tekniikkaa on lisäksi kuvattu EPS . . 0052510:ssa "Microencapsulation of water soluable polypep- tides", joka on julkaistu 27.08.86 ja EPS 0058481:ssa "Con- • · · tinuous release pharmaceutical compositions", joka on jul- :‘v kaistu 01.10.86.
• « 2 96919 vesiliuokseen huoneen tai ruumiin lämpötilassa ja jotka kuitenkin saavat aikaan tällaisten peptidien tehokkaan ja kontrolloidun vapautumisen, kun niiden yhdistelmiä annetaan pa-renteraalisesti fysiologisessa, pääasiassa vesiperäisessä ympäristössä.
Tämän keksinnön uusi ja yllättävä seuraus on, että polypep-tidit, jotka normaalisti ovat veteen liukenevia luonnossa tai kun ne on valmistettu synteesillä, voidaan edullisesti tehdä veteen liukenemattomiksi muodostamalla liukenemattomia uusia suoloja, kuten pamoichapon, parkkihapon, steariiniha-pon ja muiden ei toksisten veteen liukenemattomien happojen kanssa, ennen niiden mikrokapselointia tai dispersiota elimistössä hajoavaan polymeeriseen alustaan.
Heikonlaisesti liukenevien tai veteen liukenemattomien johdannaisten käyttö on tietysti hyvin tunnettua, jopa peptidi-alalla (Us Patent 4,010,125, palsta 7, rivi 25), kun hitaasti ainetta vapauttavia depot-annostelumuotoJa tarvitaan.
Kuitenkin kun elimistössä hajoavia polymeerejä, kuten poly-maitohappoa, polyglykolihappoa, polyhydroksivoihappoa, poly-ortho-estereitä, polyasetaaleja ja vastaavia käytetään lääkkeen vapautussysteemeinä, peptidien vapautuminen keskeyty- i l 1 mättömällä tavalla on jatkuvasti vaatinut olennaista veteen liukenevuutta. Raportoidut kokeet ovat osoittaneet, että po- ♦ · · lymeerien (kuten polylaktidin ja polylaktidi-ko-glykolidin ·** * V. esimerkiksi) hajoaminen elimistössä johtaa veden sitomiseen ja sellaisten vesikanavien tai huokosten syntymiseen, joista peptidit vuotavat ulos, koska ne ovat veteen liukenevia.
• · · « · ♦ « · · *·. Keksintömme, että peptidit voivat vapautua aineista ja mik- rokapseleista erittäin tavoitellun vapautumismallin mukaan, • · ·*.* kun niiden veteen liukenevuus vähennetään käytännölisesti katsoen nollatasolle, on yllättävää ja vastoin alan aikai- I « « : sempia opetuksia. Erityisesti havaitsimme, että tiettyjen peptidien, kuten D-Trp®-LHRH:n, vapautuminen polymeerisestä alustasta on parempaa tasaisuuden ja keston suhteen mitä veteen liukenemattomampaa peptidin lisäksi tuleva suola on.
li 3 96919 "Veteen 1 lukeneinattomuus" on täten määritelty peptidin määränä, joka voidaan mitata liuoksessa, kun suolaa dispergoi-daan tai vatkataan tislatussa vedessä 4 tunnin ajan 40°C:n lämpötilassa tai sen alapuolella, määrän ollessa 25 mg/1 tai vähemmän (0-25 ppm).
On erittäin toivottavaa antaa biologisesti aktiivisia polypeptide jä yhtäjaksoisesti ja pitkäkestoisen ajanjakson, yhdestä viikosta useisiin kuukausiin aikana. On myös erittäin toivottavaa, että vapautumiskaava on kontrolloitu, jotta vältetään peptidien epätasaiset vapautumiset terapeuttisen jakson alussa, keskivaiheilla tai lopussa. On usein havaittu, että peptidit vapautuvat elimistössä hajoavista aineista purkauksina (kutsutaan myös purkausvaikutuksiksi), joko kierron alussa tai lopussa, kun polymeerinen aine on hydro-lyysin syövyttämä.
Tämän keksinnön tärkeä piirre on vapautumiskaavan kontrollointi ja yleensä alkupurkauksen väheneminen. Veteen liukenematon peptidi vapautuu vähemmässä määrin kuin sen veteen liukenevat johdannaiset, tuottaen täten pidemmän vapautumis-,'!’« ajan ja estäen yliannostuksen antamisen potilaalle. Muutta malla normaalisti veteen liukeneva peptidi veteen liukene- t < · i mattomaksi kykenemme rajoittamaan alkupurkauksen (se on va-Ta‘.' pautuneen peptidin määrä ensimmäisten 24 tunnin aikana) alle 30 %:iin koko annoksesta.
: : : • *
Esimerkki 1 f ~ 1 • I · • t · ·*· • * r V · Viisikymmentä grammaa D,L-laktidin ja glykolidin kopolymee- riä, jossa D,L-laktidin ja glykolidin molaarinen suhde on 50/50 ja keskimääräinen molekyylipaino 50 000, liuotetaan I t ·' 950 grammaan metyleenikloridia.
i t I 1
Liuos suodatetaan millipore-suodattimen läpi tarkoituksena poistaa kaikki partikkelit ja pyrogeenit. Tähän liuokseen lisätään yksi gramma D-Trp® LHRH pamoaattia lisätään tähän 4 96919 liuokseen ja dispergoidaan sekoittajalla.
Tuloksena oleva seos pannaan pyörivään haihduttimeen ja suurin osa metyleenikloridista poistetaan vakuumissa. Näin saatu paksu dispersio kaadetaan lasilevylle ja levitetään 0,7mm:iin säädetyllä terällä.
Ilmassa kuivauksen jälkeen tuloksena olevaa filmiä kuivataan vakuumissa 48 tuntia ja puristetaan sitten paineessa 0,8 mm suuttimen läpi 70°C:n lämpötilassa. Tuloksena olevat sauvat jauhetaan -40°C:n kylmyydessä.
Tuloksena oleva rakeinen aine siivilöidään 180 jm siivilän läpi ja alamittainen fraktio kerätään ja steriloidaan gammasäteilyllä, jonka voimakkuus on 2,5 -2,8 Mrad.
»
: Esimerkki II
« · ·
Noudatetaan samaa menetelmää kuin esimerkissä 1 korvaamalla D-Trp^-LHRH pamoaatti D-TRP^-LHRH stearaattisuolalla.
Esimerkki III
Noudatetaan samaa menetelmää kuin esimerkissä I käyttäen • I __ D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2: n pamoaatti suolaa • · .1 I veteen liukenemattomana peptidinä.
t · · • · · • ·
II
· · · · • · * ·
Esimerkki IV
• · · • · • · • · ·
Esimerkin I menetelmää sovelletaan yhteen seuraavista veteen liukenemattomista pamoaattisuoloista: D-Nal(2)6 LHRH pamoaatti D-Ser(0-tBu)6 -des Gly^^-Azgly^-^-LHRH pamoaatti D-SerCBu^J^LHRHil-g) etyyliamidi pamoaatti D-Leu^-des Gly^-LHRH etyyliamidi pamoaatti 5 96919
Esimerkki V
Esimerkkien I-IV menetelmää noudatetaan käyttäen D,L lakti-di-ko-glykolidipolymeerejä, joissa molaarinen suhde oli 67% D,L laktidia 33% glykolidia, 75% D,L laktidia 25% glykolidia tai 100% D,L laktidia.
Esimerkki VI
Noudatetaan esimerkkien I-V menetelmää käyttäen yhtä seuraa-vien peptidien veteen liukenemattomista pamoaatti-, tannaat-ti- tai stearaattisuoloista: oksitosiini, vasopressiini, ACTH, kalsitoniini, epidermaalinen kasvutekijä, prolaktiini, inhibiini, interferoni, LHRH, somatostatiini, insuliini, glukagoni, sydämen natriureettinen hormomi, endorfiini, reniini-inhibiittori, GHRH, peptidi-T, tai niiden .·. : synteettisiä analogeja ja modifikaatioita.
* « · < · · ;; Vapautumismalli eläimillä (rotilla) • I ·
Implantoidun D-Trp^-LHRH pamoaatin tyypillinen vapautumismalli rotilla on seuraava: ng/ml radioaktiivisesti merkittyä D-Trp^-LHRH plasmassa (kuuden rotan keskiarvo): (t0) 0,04, :V: (1 h) 7,74, (6 h) 0,80, (2 vrk) 0,85, (4vrk) 0,77, (7 vrk) :Y: 0,25, (11 vrk) 0,12, (14 vrk) 0,11, (18 vrk) 0,11, (21 vrk) .·*: 0,14, (25 vrk) 0,18.
• « · • · · ] Edellä olevat esimerkit eivät rajoitu kuvattuihin veteen ·/:*: liukenemattomiin peptideihin tai käytettyihin elimistössä ·’**: hajoaviin peptideihin, kuten on selvää alan asiantuntijalle.
- · · ·

Claims (7)

96919
1. Menetelmä farmaseuttisesti hyväksyttävän koostumuksen valmistamiseksi, joka on suunniteltu pitkittyneelle ja kontrolloidulle peptidi lääkeaineen vapautumiselle pitkän ajanjakson kuluessa, joka koostumus käsittää polyaktidin, polyglykolidin, maitohapon ja glykolihapon kopolymeerin tai sellaisten polymeerien seoksen ja farmaseuttisesti hyväksyttävän veteen liukenemattoman peptidin, tunnettu siitä, että veteen liukenemattoman peptidin suola dispergoidaan polyaktidin, polyglykolidin, maitohapon ja glykolihapon kopolymeerin tai tällaisten polymeerien seosten liuokseen, poistetaan liuotin kuivaamalla ja muotoillaan tuloksena oleva seos kiinteiksi hiukkasiksi, jotka sopivat parenteraaliseen injektioon ja joka asetettuna vesiperäiseen fysiologis-tyyp-piseen ympäristöön vapauttaa peptidiä ainakin viikon pituisen ajanjakson, kuitenkaan vapauttamatta ensimmäisen vuorokauden aikana enempää kuin 30 % vapautumisen kokonaismäärästä.
• · .* 2. Patenttivaatimuksen l mukainen menetelmä, tunnettu siitä, että farmaseuttisesti hyväksyttävä suola on valittu pamoaat- *·· ti-, parkkihappo- ja stearaattisuolan ryhmästä. • · • · · • · ·
3. Patenttivaatimuksen 1 tai 2 mukainen menetelmä, tunnettu siitä, että veteen liukenematon peptidi on farmaseuttisesti . hyväksyttävä LHRH:n tai sen synteettisesti valmistetun • · ♦ *;;·* analogin suola.
• · · • · · :*·.· 4. Patenttivaatimuksen 3 mukainen menetelmä, tunnettu siitä, • · .***. että veteen liukenematon peptidi on D-Trp6-LHRH: n pamoaat- •. tisuola.
5. Patenttivaatimuksen 1 tai 2 mukainen menetelmä, tunnettu siitä, että liukenematon peptidi on farmaseuttisesti hyväksyttävä oksitosiinin, vasopressiinin, ACTH:n, kalsitoniinin, II 96919 epidermaalisen kasvutekijän, prolaktiinin, inhibiinin, interferonin, somatostatiinin, insuliinin, glukagonin, sydämen natriureettisen hormonin, endorfiinin, reniini-inhibiittorin, kasvuhormonia vapauttavan hormonin, peptidi T:n ja niiden synteettisten analogien ja modifikaatioiden suola.
6. Patenttivaatimuksen 5 mukainen menetelmä, tunnettu siitä, että veteen liukenematon peptidi on D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2: n pamoaattisuola.
7. Jonkin patenttivaatimuksista 1-6 mukainen menetelmä, tunnettu siitä, että koostumus on injektoitavassa muodossa ja että partikkelit vaihtelevat kooltaan 1 /xm:stä 500 Mm:iin. • · • t • « « • « · » · • « · • · • · · « · • · • · · • · · • · • · · • 1 2 3 t • · · • · · • · · • « · ♦ • · ♦ • · · 2 • · 3 • · • · • · · • » 1 ♦ ♦ • ♦ • φ β 96919
FI884297A 1987-09-21 1988-09-19 Veteen liukenemattomia polypeptidejä FI96919C (fi)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB8722134A GB2209937B (en) 1987-09-21 1987-09-21 Water insoluble polypeptides
GB8722134 1987-09-21

Publications (4)

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FI884297A0 FI884297A0 (fi) 1988-09-19
FI884297A FI884297A (fi) 1989-03-22
FI96919B true FI96919B (fi) 1996-06-14
FI96919C FI96919C (fi) 1996-09-25

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US (2) US5192741A (fi)
JP (1) JPH0713023B2 (fi)
AT (1) AT397035B (fi)
AU (1) AU611944B2 (fi)
BE (1) BE1001685A5 (fi)
CA (1) CA1326438C (fi)
CH (1) CH675968A5 (fi)
DE (2) DE122004000023I2 (fi)
DK (1) DK175311B1 (fi)
ES (1) ES2009346A6 (fi)
FI (1) FI96919C (fi)
FR (1) FR2620621B1 (fi)
GB (1) GB2209937B (fi)
GR (1) GR1002244B (fi)
IE (1) IE60608B1 (fi)
IL (1) IL87790A (fi)
IT (1) IT1225148B (fi)
LU (1) LU87340A1 (fi)
NL (1) NL193818C (fi)
NO (2) NO178604C (fi)
PT (1) PT88557B (fi)
SE (1) SE503406C2 (fi)
ZA (1) ZA886827B (fi)

Families Citing this family (193)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4997815A (en) * 1988-11-01 1991-03-05 Children's Hospital Medical Center Of Northern California Method for augmenting fetal hemoglobin by treatment with activin and/or inhibin
US5538739A (en) * 1989-07-07 1996-07-23 Sandoz Ltd. Sustained release formulations of water soluble peptides
HU221294B1 (en) * 1989-07-07 2002-09-28 Novartis Ag Process for producing retarde compositions containing the active ingredient in a polymeric carrier
PH30995A (en) * 1989-07-07 1997-12-23 Novartis Inc Sustained release formulations of water soluble peptides.
US5225205A (en) * 1989-07-28 1993-07-06 Debiopharm S.A. Pharmaceutical composition in the form of microparticles
US5439688A (en) * 1989-07-28 1995-08-08 Debio Recherche Pharmaceutique S.A. Process for preparing a pharmaceutical composition
CH679207A5 (fi) * 1989-07-28 1992-01-15 Debiopharm Sa
CH681425A5 (fi) * 1990-11-14 1993-03-31 Debio Rech Pharma Sa
EP0423484B1 (de) * 1989-10-16 1993-11-03 PCD-Polymere Gesellschaft m.b.H. Pressling mit retardierter Wirkstofffreisetzung
DE3935736A1 (de) * 1989-10-27 1991-05-02 Chemie Linz Deutschland Pressling mit retardierter wirkstofffreisetzung
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
IE912365A1 (en) * 1990-07-23 1992-01-29 Zeneca Ltd Continuous release pharmaceutical compositions
IT1243390B (it) * 1990-11-22 1994-06-10 Vectorpharma Int Composizioni farmaceutiche in forma di particelle atte al rilascio controllato di sostanze farmacologicamente attive e procedimento per la loro preparazione.
YU48420B (sh) * 1991-03-25 1998-07-10 Hoechst Aktiengesellschaft Postupak za dobijanje biološki razgradljivih mikročestica sa dugotrajnim delovanjem
CH683149A5 (fr) * 1991-07-22 1994-01-31 Debio Rech Pharma Sa Procédé pour la préparation de microsphères en matériau polymère biodégradable.
US5876452A (en) * 1992-02-14 1999-03-02 Board Of Regents, University Of Texas System Biodegradable implant
US6013853A (en) * 1992-02-14 2000-01-11 The University Of Texas System Continuous release polymeric implant carrier
US5912015A (en) 1992-03-12 1999-06-15 Alkermes Controlled Therapeutics, Inc. Modulated release from biocompatible polymers
AU668384B2 (en) * 1992-03-12 1996-05-02 Alkermes Controlled Therapeutics, Inc. Controlled release ACTH containing microspheres
US5674534A (en) * 1992-06-11 1997-10-07 Alkermes, Inc. Composition for sustained release of non-aggregated erythropoietin
US5716644A (en) * 1992-06-11 1998-02-10 Alkermes, Inc. Composition for sustained release of non-aggregated erythropoietin
US6514533B1 (en) 1992-06-11 2003-02-04 Alkermas Controlled Therapeutics, Inc. Device for the sustained release of aggregation-stabilized, biologically active agent
US5711968A (en) * 1994-07-25 1998-01-27 Alkermes Controlled Therapeutics, Inc. Composition and method for the controlled release of metal cation-stabilized interferon
US20030035845A1 (en) * 1992-06-11 2003-02-20 Zale Stephen E. Composition for sustained release of non-aggregated erythropoietin
DE4223169C1 (de) * 1992-07-10 1993-11-25 Ferring Arzneimittel Gmbh Verfahren zur Mikroverkapselung wasserlöslicher Wirkstoffe
FR2693905B1 (fr) * 1992-07-27 1994-09-02 Rhone Merieux Procédé de préparation de microsphères pour la libération prolongée de l'hormone LHRH et ses analogues, microsphères et formulations obtenues.
CA2150803C (en) * 1992-12-02 2006-01-31 Henry Auer Controlled release growth hormone containing microspheres
TW333456B (en) * 1992-12-07 1998-06-11 Takeda Pharm Ind Co Ltd A pharmaceutical composition of sustained-release preparation the invention relates to a pharmaceutical composition of sustained-release preparation which comprises a physiologically active peptide.
UA61046C2 (en) 1992-12-07 2003-11-17 Takeda Chemical Industries Ltd Sustained-release preparation and method for its manufacture
US6090925A (en) 1993-03-09 2000-07-18 Epic Therapeutics, Inc. Macromolecular microparticles and methods of production and use
US5981719A (en) 1993-03-09 1999-11-09 Epic Therapeutics, Inc. Macromolecular microparticles and methods of production and use
EP0626170A3 (en) * 1993-05-10 1996-03-27 Sandoz Ltd Stabilization of pharmacoligically active compounds in controlled release compositions.
US5635216A (en) * 1993-12-16 1997-06-03 Eli Lilly And Company Microparticle compositions containing peptides, and methods for the preparation thereof
US6087324A (en) * 1993-06-24 2000-07-11 Takeda Chemical Industries, Ltd. Sustained-release preparation
CA2178592C (en) * 1993-12-09 2009-07-28 Jurgen Engel Long-acting injection suspensions and a process for their preparation
DE4342092B4 (de) * 1993-12-09 2007-01-11 Zentaris Gmbh Langwirkende Injektionssuspension und Verfahren zur Herstellung
US5569468A (en) * 1994-02-17 1996-10-29 Modi; Pankaj Vaccine delivery system for immunization, using biodegradable polymer microspheres
US5417982A (en) * 1994-02-17 1995-05-23 Modi; Pankaj Controlled release of drugs or hormones in biodegradable polymer microspheres
US5763416A (en) 1994-02-18 1998-06-09 The Regent Of The University Of Michigan Gene transfer into bone cells and tissues
US20020193338A1 (en) * 1994-02-18 2002-12-19 Goldstein Steven A. In vivo gene transfer methods for wound healing
US5942496A (en) 1994-02-18 1999-08-24 The Regent Of The University Of Michigan Methods and compositions for multiple gene transfer into bone cells
US6074840A (en) 1994-02-18 2000-06-13 The Regents Of The University Of Michigan Recombinant production of latent TGF-beta binding protein-3 (LTBP-3)
US5962427A (en) 1994-02-18 1999-10-05 The Regent Of The University Of Michigan In vivo gene transfer methods for wound healing
US6551618B2 (en) * 1994-03-15 2003-04-22 University Of Birmingham Compositions and methods for delivery of agents for neuronal regeneration and survival
US5430021A (en) * 1994-03-18 1995-07-04 Pharmavene, Inc. Hydrophobic drug delivery systems
ES2258495T3 (es) * 1994-04-08 2006-09-01 Qlt Usa, Inc. Composiciones de administracion liquida de farmacos.
IE75744B1 (en) * 1995-04-03 1997-09-24 Elan Corp Plc Controlled release biodegradable micro- and nanospheres containing cyclosporin
US5922253A (en) * 1995-05-18 1999-07-13 Alkermes Controlled Therapeutics, Inc. Production scale method of forming microparticles
CA2224381A1 (en) 1995-06-27 1997-01-16 Takeda Chemical Industries, Ltd. Method of producing sustained-release preparation
EP0850051A2 (en) * 1995-08-31 1998-07-01 Alkermes Controlled Therapeutics, Inc. Composition for sustained release of an agent
US5942253A (en) * 1995-10-12 1999-08-24 Immunex Corporation Prolonged release of GM-CSF
FR2748205A1 (fr) * 1996-05-06 1997-11-07 Debio Rech Pharma Sa Compositions pharmaceutiques pour la liberation controlee de principes actifs insolubles
US5817343A (en) * 1996-05-14 1998-10-06 Alkermes, Inc. Method for fabricating polymer-based controlled-release devices
US5817627A (en) 1996-06-14 1998-10-06 Theratechnologies Inc. Long-acting galenical formulation for GRF peptides
US5945128A (en) * 1996-09-04 1999-08-31 Romano Deghenghi Process to manufacture implants containing bioactive peptides
US20070185032A1 (en) * 1996-12-11 2007-08-09 Praecis Pharmaceuticals, Inc. Pharmaceutical formulations for sustained drug delivery
US5968895A (en) 1996-12-11 1999-10-19 Praecis Pharmaceuticals, Inc. Pharmaceutical formulations for sustained drug delivery
JP4642946B2 (ja) * 1996-12-20 2011-03-02 アルザ コーポレイション ゲル組成物および方法
WO1998032423A1 (en) * 1997-01-29 1998-07-30 Takeda Chemical Industries, Ltd. Sustained-release microspheres, their production and use
IL133105A (en) * 1997-06-04 2004-09-27 Debio Rech Pharma Sa Implants for controlled release of pharmaceutically active principles and method for making same
US7923250B2 (en) 1997-07-30 2011-04-12 Warsaw Orthopedic, Inc. Methods of expressing LIM mineralization protein in non-osseous cells
AU745122B2 (en) 1997-07-30 2002-03-14 Emory University Novel bone mineralization proteins, DNA, vectors, expression systems
US5989463A (en) 1997-09-24 1999-11-23 Alkermes Controlled Therapeutics, Inc. Methods for fabricating polymer-based controlled release devices
US6617321B2 (en) 1997-09-30 2003-09-09 Eli Lilly And Company 2-methyl-thieno-benzodiazepine formulation
US7128927B1 (en) 1998-04-14 2006-10-31 Qlt Usa, Inc. Emulsions for in-situ delivery systems
US6143314A (en) * 1998-10-28 2000-11-07 Atrix Laboratories, Inc. Controlled release liquid delivery compositions with low initial drug burst
IT1304152B1 (it) * 1998-12-10 2001-03-08 Mediolanum Farmaceutici Srl Composizioni comprendenti un peptide ed acido polilattico-glicolicoatte alla preparazione di impianti sottocutanei aventi un prolungato
KR100321854B1 (ko) * 1998-12-30 2002-08-28 동국제약 주식회사 루테이나이징 호르몬 릴리싱 호르몬 동족체를 함유하는 장기 서방출성 미립구 및 그의 제조방법
US7018654B2 (en) * 1999-03-05 2006-03-28 New River Pharmaceuticals Inc. Pharmaceutical composition containing an active agent in an amino acid copolymer structure
US6716452B1 (en) 2000-08-22 2004-04-06 New River Pharmaceuticals Inc. Active agent delivery systems and methods for protecting and administering active agents
AU3556400A (en) 1999-03-17 2000-10-04 Novartis Ag Pharmaceutical compositions
ES2169980B1 (es) 1999-12-17 2003-11-01 Lipotec Sa Microcapsulas para la liberacion prolongada de farmacos.
US6465425B1 (en) 2000-02-10 2002-10-15 Alkermes Controlled Therapeutics, Inc. Microencapsulation and sustained release of biologically active acid-stable or free sulfhydryl-containing proteins
US20030211974A1 (en) * 2000-03-21 2003-11-13 Brodbeck Kevin J. Gel composition and methods
US6362308B1 (en) 2000-08-10 2002-03-26 Alkermes Controlled Therapeutics Inc. Ii Acid end group poly(d,l-lactide-co-glycolide) copolymers high glycolide content
SE517422C2 (sv) * 2000-10-06 2002-06-04 Bioglan Ab Farmaceutiskt acceptabel stärkelse
EP1328258B1 (en) * 2000-10-06 2008-10-01 Pacira Pharmaceuticals Inc A controlled-release, parenterally administrable microparticle preparation
SE517421C2 (sv) 2000-10-06 2002-06-04 Bioglan Ab Mikropartiklar, lämpade för parenteral administration, väsentligen bestående av stärkelse med minst 85 % amylopektin och med reducerad molekylvikt, samt framställning därav
US8394813B2 (en) 2000-11-14 2013-03-12 Shire Llc Active agent delivery systems and methods for protecting and administering active agents
SE518007C2 (sv) 2000-11-16 2002-08-13 Bioglan Ab Förfarande för framställning av mikropartiklar
SE518008C2 (sv) * 2000-11-16 2002-08-13 Bioglan Ab Parenteralt administrerbara mikropartiklar och förfarande för framställning av desamma
DE60130580T2 (de) * 2000-12-27 2008-06-12 Ares Trading S.A. Lipidmikropartikel mittels kryogenischer mikronisierung
US20070142325A1 (en) * 2001-01-08 2007-06-21 Gustavsson Nils O Starch
JP2004535431A (ja) 2001-06-22 2004-11-25 サザン バイオシステムズ， インコーポレイテッド ゼロ次長期放出同軸インプラント
EP1413315A4 (en) * 2001-08-03 2006-08-16 Takeda Pharmaceutical DRUGS WITH CONTINUOUS RELEASE
US20060014697A1 (en) * 2001-08-22 2006-01-19 Travis Mickle Pharmaceutical compositions for prevention of overdose or abuse
US7169752B2 (en) * 2003-09-30 2007-01-30 New River Pharmaceuticals Inc. Compounds and compositions for prevention of overdose of oxycodone
US7105181B2 (en) * 2001-10-05 2006-09-12 Jagotec, Ag Microparticles
US20040043938A1 (en) * 2001-11-06 2004-03-04 Dinesh Purandare Combination therapy for estrogen-dependent disorders
SE0201599D0 (sv) * 2002-03-21 2002-05-30 Skyepharma Ab Microparticles
US20090035260A1 (en) * 2002-07-29 2009-02-05 Therapicon Srl Enhanced nasal composition of active peptide
US7658998B2 (en) * 2003-01-22 2010-02-09 Alkermes Controlled Therapeutics, Inc. Method of preparing sustained release microparticles
BRPI0407071B8 (pt) 2003-01-28 2021-05-25 Ironwood Pharmaceuticals Inc peptídeo purificado, seu método de produção e composição farmacêutica para o tratamento de distúrbios gastrointestinais
US7772188B2 (en) 2003-01-28 2010-08-10 Ironwood Pharmaceuticals, Inc. Methods and compositions for the treatment of gastrointestinal disorders
GB0304726D0 (en) * 2003-03-01 2003-04-02 Ardana Bioscience Ltd New Process
ATE510605T1 (de) * 2003-03-14 2011-06-15 Univ Columbia Systeme und verfahren für auf blut basierende therapien mit einer membranlosen mikrofluid- austauschvorrichtung
US20060076295A1 (en) 2004-03-15 2006-04-13 The Trustees Of Columbia University In The City Of New York Systems and methods of blood-based therapies having a microfluidic membraneless exchange device
US20070207211A1 (en) * 2003-04-10 2007-09-06 Pr Pharmaceuticals, Inc. Emulsion-based microparticles and methods for the production thereof
WO2005003180A2 (en) * 2003-04-10 2005-01-13 Pr Pharmaceuticals A method for the production of emulsion-based micro particles
US20060193825A1 (en) * 2003-04-29 2006-08-31 Praecis Phamaceuticals, Inc. Pharmaceutical formulations for sustained drug delivery
US20050112087A1 (en) * 2003-04-29 2005-05-26 Musso Gary F. Pharmaceutical formulations for sustained drug delivery
ES2625343T3 (es) * 2003-07-15 2017-07-19 Evonik Corporation Método para la preparación de formulaciones de liberación controlada
JP5165240B2 (ja) 2003-07-23 2013-03-21 ピーアール ファーマシューティカルズ， インコーポレイテッド 徐放組成物
US6987111B2 (en) * 2003-08-06 2006-01-17 Alkermes Controlled Therapeutics, Ii Aripiprazole, olanzapine and haloperidol pamoate salts
US7309232B2 (en) * 2003-10-10 2007-12-18 Dentigenix Inc. Methods for treating dental conditions using tissue scaffolds
PT1682537E (pt) 2003-11-05 2012-06-20 Sarcode Bioscience Inc Moduladores de adesão celular
ITMI20040235A1 (it) * 2004-02-13 2004-05-13 Therapicon Srl Preparazione farmaceutica per il cavo orale
KR101201638B1 (ko) * 2004-04-23 2012-11-15 암젠 인코포레이티드 서방성 제형
GB0412866D0 (en) * 2004-06-09 2004-07-14 Novartis Ag Organic compounds
PT1781264E (pt) 2004-08-04 2013-10-16 Evonik Corp Métodos para o fabrico de dispositivis de administração e dispositivos para a mesma
ES2255426B1 (es) * 2004-10-19 2007-08-16 Gp Pharm, S.A. Formulacion farmaceutica que comprende microcapsulas de estatinas suspendidas en ester alquilicos de acidos grasos poliinsaturados (pufa).
EP1674082A1 (de) 2004-12-22 2006-06-28 Zentaris GmbH Verfahren zur Herstellung von sterilen Suspensionen oder Lyophilisaten schwerlöslicher basischer Peptidkomplexe, diese enthaltende pharmazeutische Formulierungen sowie ihre Verwendung als Arzneimittel
PT1838716E (pt) * 2005-01-05 2011-07-15 Lilly Co Eli Di-hidrato de pamoato de olanzapina
DE602005026998D1 (de) * 2005-01-14 2011-04-28 Camurus Ab Somatostatin-analog-formulierungen
DE602005020359D1 (de) * 2005-01-14 2010-05-12 Camurus Ab Topische bioadhäsive formulierungen
US9649382B2 (en) 2005-01-14 2017-05-16 Camurus Ab Topical bioadhesive formulations
CA2595385C (en) 2005-01-21 2011-01-25 Camurus Ab Pharmaceutical lipid compositions
KR20070100411A (ko) * 2005-02-01 2007-10-10 아테뉴온, 엘엘씨 Ａｃ－ＰＨＳＣＮ－ＮＨ２의 산 부가 염
AU2006241072A1 (en) * 2005-04-25 2006-11-02 Amgen Inc. Biodegradable peptide sustained release compositions containing porogens
WO2006125119A1 (en) * 2005-05-17 2006-11-23 Sarcode Corporation Compositions and methods for treatment of eye disorders
DK1888031T3 (da) * 2005-06-06 2013-02-18 Camurus Ab GLP-1-analogformuleringer
AU2006265814B2 (en) * 2005-06-30 2012-05-10 Ipsen Pharma S.A.S. GLP-1 pharmaceutical compositions
US7942867B2 (en) * 2005-11-09 2011-05-17 The Invention Science Fund I, Llc Remotely controlled substance delivery device
KR100722607B1 (ko) * 2006-05-11 2007-05-28 주식회사 펩트론 분산성 및 주사 투여능이 향상된 서방성 미립구의 제조방법
US7403325B2 (en) * 2006-05-19 2008-07-22 Xerox Corporation Electrophoretic display device
AU2007253702A1 (en) * 2006-05-22 2007-11-29 The Trustees Of Columbia University In The City Of New York Systems and methods of microfluidic membraneless exchange using filtration of extraction fluid outlet streams
US20080075777A1 (en) * 2006-07-31 2008-03-27 Kennedy Michael T Apparatus and methods for preparing solid particles
US7858663B1 (en) 2007-10-31 2010-12-28 Pisgah Laboratories, Inc. Physical and chemical properties of thyroid hormone organic acid addition salts
US7718649B1 (en) 2006-11-10 2010-05-18 Pisgah Labs, Inc. Physical states of a pharmaceutical drug substance
US8211905B1 (en) 2007-05-22 2012-07-03 Pisgah Laboratories, Inc. Opioid salts and formulations exhibiting anti-abuse and anti-dose dumping properties
US20080293695A1 (en) 2007-05-22 2008-11-27 David William Bristol Salts of physiologically active and psychoactive alkaloids and amines simultaneously exhibiting bioavailability and abuse resistance
US8039461B1 (en) 2006-11-10 2011-10-18 Pisgah Laboratories, Inc. Physical states of a pharmaceutical drug substance
US10183001B1 (en) 2007-05-22 2019-01-22 Pisgah Laboratories, Inc. Opioid and attention deficit hyperactivity disorder medications possessing abuse deterrent and anti-dose dumping safety features
US8329720B1 (en) 2007-05-22 2012-12-11 Pisgah Laboratories, Inc. Opioid salts and formulations exhibiting abuse deterrent and anti-dose dumping properties
US9421266B2 (en) 2007-05-22 2016-08-23 Pisgah Laboratories, Inc. Safety of pseudoephedrine drug products
US20100120694A1 (en) 2008-06-04 2010-05-13 Synergy Pharmaceuticals, Inc. Agonists of Guanylate Cyclase Useful for the Treatment of Gastrointestinal Disorders, Inflammation, Cancer and Other Disorders
US8969514B2 (en) 2007-06-04 2015-03-03 Synergy Pharmaceuticals, Inc. Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases
US7879802B2 (en) 2007-06-04 2011-02-01 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
AP3000A (en) * 2007-06-06 2014-10-31 Debiopharm Res & Mfg Sa Slow release pharmaceutical composition made of microparticles
GB0711656D0 (en) * 2007-06-15 2007-07-25 Camurus Ab Formulations
GB0716385D0 (en) 2007-08-22 2007-10-03 Camurus Ab Formulations
AU2008317473B2 (en) * 2007-10-19 2014-07-17 Bausch + Lomb Ireland Limited Compositions and methods for treatment of diabetic retinopathy
US8728528B2 (en) 2007-12-20 2014-05-20 Evonik Corporation Process for preparing microparticles having a low residual solvent volume
BRPI0907473A2 (pt) * 2008-02-04 2019-09-24 Univ Columbia métodos, sistemas e dispositivos de separação de fluidos
US8883863B1 (en) 2008-04-03 2014-11-11 Pisgah Laboratories, Inc. Safety of psuedoephedrine drug products
US20090258069A1 (en) * 2008-04-15 2009-10-15 John Burnier Delivery of LFA-1 antagonists to the gastrointestinal system
WO2009139817A2 (en) 2008-04-15 2009-11-19 Sarcode Corporation Crystalline pharmaceutical and methods of preparation and use thereof
ES2624828T3 (es) 2008-07-16 2017-07-17 Synergy Pharmaceuticals Inc. Agonistas de la guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros
DK2326336T3 (en) 2008-07-30 2015-07-27 Mesynthes Ltd Tissue support structures from the extracellular matrix of a preform
GB0815435D0 (en) 2008-08-22 2008-10-01 Camurus Ab Formulations
KR101688666B1 (ko) 2008-08-29 2016-12-21 젠자임 코포레이션 제어 방출성 펩티드 제형
US20100062057A1 (en) * 2008-09-10 2010-03-11 Pronova BioPharma Norge AS. Formulation
US11395811B2 (en) 2009-03-09 2022-07-26 Pronova Biopharma Norge As Compositions comprising a fatty acid oil mixture comprising EPA and DHA in free acid form and a surfactant, and methods and uses thereof
BR112012006443A2 (pt) * 2009-09-22 2017-07-25 Evonik Degussa Corp dispositivos de implante que apresentam configurações de cargas variáveis de agentes bioativos
WO2011050175A1 (en) * 2009-10-21 2011-04-28 Sarcode Corporation Crystalline pharmaceutical and methods of preparation and use thereof
ES2364011B1 (es) 2009-11-20 2013-01-24 Gp Pharm, S.A. Cápsulas de principios activos farmacéuticos y ésteres de ácidos grasos poliinsaturados para el tratamiento de enfermedades cardiovasculares.
ES2363965B1 (es) 2009-11-20 2013-01-24 Gp Pharm S.A. Cápsulas de principios activos betabloqueantes y ésteres de ácidos grasos poliinsaturados.
ES2363964B1 (es) 2009-11-20 2012-08-22 Gp Pharm, S.A. Cápsulas de principios activos farmacéuticos y ésteres de ácidos grasos poliinsaturados.
SG181446A1 (en) 2009-12-23 2012-07-30 Defiante Farmaceutica Sa Combination composition useful for treating cardiovascular diseases
USRE49251E1 (en) 2010-01-04 2022-10-18 Mapi Pharma Ltd. Depot systems comprising glatiramer or pharmacologically acceptable salt thereof
LT2398488T (lt) * 2010-01-04 2019-01-25 Mapi Pharma Limited Depo sistema, apimanti glatiramero acetatą
ES2383271B1 (es) 2010-03-24 2013-08-01 Lipotec S.A. Procedimiento de tratamiento de fibras y/o materiales textiles
ES2385240B1 (es) 2010-07-26 2013-09-23 Gp-Pharm, S.A. Cápsulas de principios activos farmacéuticos y ácidos grasos poliinsaturados para el tratamiento de enfermedades de la próstata.
US9616097B2 (en) 2010-09-15 2017-04-11 Synergy Pharmaceuticals, Inc. Formulations of guanylate cyclase C agonists and methods of use
MX362218B (es) 2011-05-04 2019-01-09 Balance Therapeutics Inc Derivados de pentilentetrazol.
WO2013072767A1 (en) 2011-11-18 2013-05-23 Pronova Biopharma Norge As Compositions and preconcentrates comprising at least one salicylate and omega-3 fatty acid oil mixture
EP2833740B1 (en) 2012-04-04 2016-09-14 Pronova BioPharma Norge AS Compositions comprising omega-3 fatty acids and vitamin d for acne vulgaris and/or eczema, and methods and uses thereof
US9585896B2 (en) 2012-04-04 2017-03-07 Pronova Biopharma Norge As Compositions comprising omega-3 fatty acids and vitamin D for psoriasis, and methods and uses thereof
CN104284673B (zh) * 2012-05-14 2018-02-13 帝人株式会社 灭菌组合物
BR112014029425A2 (pt) 2012-05-25 2017-06-27 Camurus Ab pré-formulação, dispositivo de administração pré-cheio, kit, processo para a formação de uma pré-formulação, usos de mistura e de um solvente polar, e, método para o tratamento de um sujeito
IN2015DN00847A (fi) 2012-07-25 2015-06-12 Sarcode Bioscience Inc
US9545446B2 (en) 2013-02-25 2017-01-17 Synergy Pharmaceuticals, Inc. Agonists of guanylate cyclase and their uses
JP6537980B2 (ja) 2013-02-28 2019-07-03 プロノヴァ・バイオファーマ・ノルゲ・アーエスＰｒｏｎｏｖａ ＢｉｏＰｈａｒｍａ Ｎｏｒｇｅ ＡＳ 脂質化合物、トリグリセリドおよび界面活性剤を含む組成物、ならびにその使用方法
FR3002735B1 (fr) * 2013-03-04 2015-07-03 Virbac Composition orale nutritionnelle et medicamenteuse a usage veterinaire
FR3002736B1 (fr) 2013-03-04 2015-06-26 Virbac Composition orale nutritionnelle et medicamenteuse a usage veterinaire
AU2014235209B2 (en) 2013-03-15 2018-06-14 Bausch Health Ireland Limited Guanylate cyclase receptor agonists combined with other drugs
CA2905438A1 (en) 2013-03-15 2014-09-25 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase and their uses
CA2926691A1 (en) 2013-10-10 2015-04-16 Synergy Pharmaceuticals, Inc. Agonists of guanylate cyclase useful for the treatment of opioid induced dysfunctions
US20160151511A1 (en) 2014-12-02 2016-06-02 Antriabio, Inc. Proteins and protein conjugates with increased hydrophobicity
US9925233B2 (en) 2015-01-30 2018-03-27 Par Pharmaceutical, Inc. Vasopressin formulations for use in treatment of hypotension
US9744209B2 (en) 2015-01-30 2017-08-29 Par Pharmaceutical, Inc. Vasopressin formulations for use in treatment of hypotension
US9744239B2 (en) 2015-01-30 2017-08-29 Par Pharmaceutical, Inc. Vasopressin formulations for use in treatment of hypotension
US9687526B2 (en) 2015-01-30 2017-06-27 Par Pharmaceutical, Inc. Vasopressin formulations for use in treatment of hypotension
US9750785B2 (en) 2015-01-30 2017-09-05 Par Pharmaceutical, Inc. Vasopressin formulations for use in treatment of hypotension
US9937223B2 (en) 2015-01-30 2018-04-10 Par Pharmaceutical, Inc. Vasopressin formulations for use in treatment of hypotension
RU2017128112A (ru) 2015-07-15 2019-08-15 Интернэшнл Эдвансд Рисёрч Сентр Фо Паудер Металлурджи Энд Нью Материалс (Арси) Усовершенствованный способ получения термоизоляционного продукта из аэрогеля диоксида кремния с повышенной эффективностью
CA3009814A1 (en) 2016-01-11 2017-07-20 Synergy Pharmaceuticals, Inc. Formulations and methods for treating ulcerative colitis
US12097292B2 (en) 2016-08-28 2024-09-24 Mapi Pharma Ltd. Process for preparing microparticles containing glatiramer acetate
CA3050086A1 (en) 2017-03-26 2018-10-04 Mapi Pharma Ltd. Glatiramer depot systems for treating progressive forms of multiple sclerosis
CA3077011A1 (en) 2017-09-26 2019-04-04 Nanomi B.V. Method for preparing micro-particles by double emulsion technique
CN110123658B (zh) * 2019-05-22 2022-07-15 上海璞萃生物科技有限公司 一种具有自组装聚集体结构的超分子多肽及其制备方法
IT202000017191A1 (it) 2020-07-15 2022-01-15 Xbrane Biopharma Ab Procedimento senza acqua per preparare una composizione farmaceutica per un rilascio più prolungato e controllato di triptorelina o di un suo sale
CN116803378B (zh) * 2023-08-24 2023-11-17 北京福元医药股份有限公司 一种格列齐特缓释片剂及其制备方法

Family Cites Families (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3773919A (en) * 1969-10-23 1973-11-20 Du Pont Polylactide-drug mixtures
US4010125A (en) * 1975-06-12 1977-03-01 Schally Andrew Victor [D-Trp6 ]-LH-RH and intermediates therefor
US4622244A (en) * 1979-09-04 1986-11-11 The Washington University Process for preparation of microcapsules
US4293539A (en) * 1979-09-12 1981-10-06 Eli Lilly And Company Controlled release formulations and method of treatment
US4341767A (en) * 1980-10-06 1982-07-27 Syntex Inc. Nonapeptide and decapeptide analogs of LHRH, useful as LHRH antagonists
US4675189A (en) * 1980-11-18 1987-06-23 Syntex (U.S.A.) Inc. Microencapsulation of water soluble active polypeptides
PH19942A (en) * 1980-11-18 1986-08-14 Sintex Inc Microencapsulation of water soluble polypeptides
IE52535B1 (en) * 1981-02-16 1987-12-09 Ici Plc Continuous release pharmaceutical compositions
ATE37983T1 (de) * 1982-04-22 1988-11-15 Ici Plc Mittel mit verzoegerter freigabe.
US4667014A (en) * 1983-03-07 1987-05-19 Syntex (U.S.A.) Inc. Nonapeptide and decapeptide analogs of LHRH, useful as LHRH antagonists
CH660488A5 (en) * 1982-12-17 1987-04-30 Sandoz Ag (Co)oligomeric hydroxycarboxylic acid derivatives, the preparation thereof, and the use thereof in pharmaceutical compositions
CH661206A5 (fr) * 1983-09-23 1987-07-15 Debiopharm Sa Procede pour la preparation d'un medicament destine au traitement de maladies hormonodependantes.
JPS60100516A (ja) * 1983-11-04 1985-06-04 Takeda Chem Ind Ltd 徐放型マイクロカプセルの製造法
US4547370A (en) * 1983-11-29 1985-10-15 The Salk Institute For Biological Studies GnRH Antagonists
US4708861A (en) * 1984-02-15 1987-11-24 The Liposome Company, Inc. Liposome-gel compositions
US4632979A (en) * 1984-06-18 1986-12-30 Tulane Educational Fund Therapeutic LHRH analogs
GB8416234D0 (en) * 1984-06-26 1984-08-01 Ici Plc Biodegradable amphipathic copolymers
US4647653A (en) * 1984-08-23 1987-03-03 Tulane Educational Fund Therapeutic peptides
ZA855567B (en) * 1984-08-31 1986-03-26 Salk Inst For Biological Studi Insulin-selective somatostatin analogs
CH660302A5 (fr) * 1984-10-17 1987-04-15 Debiopharm Sa Procede de micro-encapsulation en phase heterogene de substances medicamenteuses hydrosolubles.
JPS61172813A (ja) * 1985-01-28 1986-08-04 Japan Atom Energy Res Inst ポリ乳酸を担体とする徐放性複合体の製造方法
EP0190833B1 (en) * 1985-02-07 1991-03-27 Takeda Chemical Industries, Ltd. Method for producing microcapsule
US4677193A (en) * 1985-02-22 1987-06-30 The Salk Institute For Biological Studies Peptides containing an aliphatic-aromatic ketone side chain
US4666704A (en) * 1985-05-24 1987-05-19 International Minerals & Chemical Corp. Controlled release delivery system for macromolecules
IL79134A (en) * 1985-07-29 1991-06-10 American Cyanamid Co Continuous release peptide implants for parenteral administration
US4962091A (en) * 1986-05-23 1990-10-09 Syntex (U.S.A.) Inc. Controlled release of macromolecular polypeptides
US4897268A (en) * 1987-08-03 1990-01-30 Southern Research Institute Drug delivery system and method of making the same
US5089471A (en) * 1987-10-01 1992-02-18 G. D. Searle & Co. Peptidyl beta-aminoacyl aminodiol carbamates as anti-hypertensive agents
DE3734223A1 (de) * 1987-10-09 1989-04-20 Boehringer Ingelheim Kg Implantierbares, biologisch abbaubares wirkstofffreigabesystem
CA2012901A1 (en) * 1989-04-05 1990-10-05 Quirico Branca Amino acid derivatives

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BE1001685A5 (fr) 1990-02-06
NL193818C (nl) 2000-12-04
FI884297A0 (fi) 1988-09-19
AU611944B2 (en) 1991-06-27
FI884297A (fi) 1989-03-22
DK518988D0 (da) 1988-09-16
GB8722134D0 (en) 1987-10-28
PT88557B (pt) 1992-11-30
US5776885A (en) 1998-07-07
SE8803321L (sv) 1989-03-22
NO884154D0 (no) 1988-09-19
SE8803321D0 (sv) 1988-09-20
ZA886827B (en) 1989-05-30
NO178604B (no) 1996-01-22
CA1326438C (en) 1994-01-25
DE122004000023I2 (de) 2009-05-07
IE60608B1 (en) 1994-07-27
DE3822459A1 (de) 1989-03-30
IE882727L (en) 1989-03-21
GB2209937B (en) 1991-07-03
ES2009346A6 (es) 1989-09-16
NO884154L (no) 1989-03-22
NL8802323A (nl) 1989-04-17
GR880100619A (el) 1989-06-22
IT8805213A0 (it) 1988-09-20
AU2232688A (en) 1989-03-23
DE3822459C2 (de) 1994-07-07
LU87340A1 (fr) 1989-04-06
US5192741A (en) 1993-03-09
NO2005012I2 (no) 2008-12-01
SE503406C2 (sv) 1996-06-10
ATA223488A (de) 1993-06-15
FR2620621B1 (fr) 1993-02-19
DK518988A (da) 1989-03-22
CH675968A5 (fi) 1990-11-30
PT88557A (pt) 1988-10-01
GR1002244B (en) 1996-04-22
DK175311B1 (da) 2004-08-16
NO178604C (no) 1996-05-02
IT1225148B (it) 1990-11-02
JPH01121222A (ja) 1989-05-12

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