HRP20201609T1 - Biorazgradivi hidrogelovi netopivi u vodi bazirani na polietilenglikolu - Google Patents
Biorazgradivi hidrogelovi netopivi u vodi bazirani na polietilenglikolu Download PDFInfo
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- HRP20201609T1 HRP20201609T1 HRP20201609TT HRP20201609T HRP20201609T1 HR P20201609 T1 HRP20201609 T1 HR P20201609T1 HR P20201609T T HRP20201609T T HR P20201609TT HR P20201609 T HRP20201609 T HR P20201609T HR P20201609 T1 HRP20201609 T1 HR P20201609T1
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- biodegradable hydrogel
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- A61K47/60—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 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
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Claims (37)
1. Biorazgradivi hidrogel netopiv u vodi baziran na poli(etilenglikolu), koji sadrži dijelove okosnice glavnog lanca povezane zajedno preko dijelova poprečno umreženih povezivača, pri čemu svaki dio poprečno umreženih povezivača završava s najmanje dvije hidrolitički razgradive veze, naznačen time, da dijelovi glavne okosnice imaju molekularnu masu u rasponu od 1 kDa do 20 kDa i imaju strukturu C*-(A-Hyp)x, gdje
C* je razgranata jezgra,
A je polimerni lanac na bazi poli(etilenglikola),
Hyp je hiper-razgranati dendritički dio skupine,
x je cijeli broj od 3 do 16;
te pritom hiper-razgranati dendritički dio skupine nadalje obuhvaća reaktivne funkcionalne skupine i međupovezane funkcionalne skupine.
2. Biorazgradivi hidrogel prema patentnom zahtjevu 1, naznačen time, da razgranata jezgra obuhvaća poliakohol, oligoalkohol, poliamin ili oligoamin u spojenom obliku.
3. Biorazgradivi hidrogel prema patentnom zahtjevu 1 ili 2, naznačen time, da razgranata jezgra obuhvaća pentaeritritol, tripentaeritritol, heksaglicerin, sukrozu, sorbitol, fruktozu, manitol, glukozu, celulozu, amilozu, škrob, hidroksilakilni škrob, polivinilalkohol, dekstran, hijaluronan, trilizin, tetralizin, pentalizin, heksalizin, heptalizin, oktalizin, nonalizin, dekalizin, undekalizin, dedekalizin, tridekalizin, tetradekalizin, pentadekalizin, oligolizin, polietilenimin ili polivinilamin u spojenom obliku.
4. Biorazgradivi hidrogel prema bilo kojem od patentnih zahtjeva 1 do 3, naznačen time, da razgranata jezgra obuhvaća pentaeritritol, trilizin, tetralizin, pentalizin, heksalizin, heptalizin, oligolizin, PEI male molekularne mase, heksaglicerin ili tripentaeritritol u spojenom obliku.
5. Biorazgradivi hidrogel prema bilo kojem od patentnih zahtjeva 1 do 4, naznačen time, da x je cijeli broj od 4 do 8.
6. Biorazgradivi hidrogel prema bilo kojem od patentnih zahtjeva 1 do 5, naznačen time, da svaka Hyp ima molekularnu masu u rasponu od 0,4 kDa do 4 kDa.
7. Biorazgradivi hidrogel prema bilo kojem od patentnih zahtjeva 1 do 6, naznačen time, da dijelovi poprečnog povezivača imaju molekularnu masu u rasponu od 0,5 kDa do 5 kDa, te time da je svaki dio poprečnog povezivača baziran na PEG.
8. Biorazgradivi hidrogel prema bilo kojem od patentnih zahtjeva 1 do 7, naznačen time, da svaki dio glavne okosnice obuhvaća u zbroju najmanje 16 međupovezanih biorazgradivih i reaktivnih funkcionalnih skupina.
9. Biorazgradivi hidrogel prema bilo kojem od patentnih zahtjeva 1 do 8, naznačen time, da dijelovi glavne okosnice imaju kvaterni ugljik sljedeće formule:
C(A-Hyp)4,
u kojoj je svaki A neovisno polimerni lanac na bazi poli(etilenglikola), koji je završno priključen na kvaterni ugljik pomoću permanentne kovalentne veze i udaljeni kraj polimernog lanca je kovalentno povezan s dendritičkim dijelom Hyp-skupine, dok svaki dio dendritičke Hyp-skupine posjeduje najmanje četiri funkcionalne skupine koje predstavljaju međupovezane i reaktivne funkcionalne skupine.
10. Biorazgradivi hidrogel prema bilo kojem od patentnih zahtjeva 1 do 9, naznačen time, da je svaki A neovisno odabran iz formule:
–(CH2)nl(OCH2CH2)nX-, gdje
nl je 1 ili 2;
n je cijeli broj u rasponu od 5 do 50; i
X je kemijska funkcionalna skupina koja kovalentno povezuje A i Hyp.
11. Biorazgradivi hidrogel prema bilo kojem od patentnih zahtjeva 1 do 10, naznačen time, da Hyp uvijek posjeduje najmanje tri grane i najmanje četiri reaktivne funkcionalne skupine.
12. Biorazgradivi hidrogel prema bilo kojem od patentnih zahtjeva 1 do 11, naznačen time, da Hyp je hiper-razgranati polipeptid.
13. Biorazgradivi hidrogel prema bilo kojem od patentnih zahtjeva 1 do 12, naznačen time, da Hyp sadrži lizine u spojenom obliku.
14. Biorazgradivi hidrogel prema bilo kojem od patentnih zahtjeva 1 do 13, naznačen time, da se svaki dio Hyp-skupine sastoji od 5 do 32 lizina.
15. Biorazgradivi hidrogel prema bilo kojem od patentnih zahtjeva 1 do 14, naznačen time, da Hyp sadrži heptalizinil.
16. Biorazgradivi hidrogel prema bilo kojem od patentnih zahtjeva 1 do 15, naznačen time, da dijelovi glavne okosnice obuhvaćaju razgranatu jezgru sljedeće formule:
[image]
u kojoj crtkana linija označava priključenje na preostatak od dijela glavne okosnice.
17. Biorazgradivi hidrogel prema bilo kojem od patentnih zahtjeva 1 do 16, naznačen time, da dijelovi glavne okosnice obuhvaćaju strukturu sljedeće formule:
[image]
u kojoj n je cijeli broj od 5 do 50 i crtkana linija označava priključenje na ostatak od molekule.
18. Biorazgradivi hidrogel prema bilo kojem od patentnih zahtjeva 1 do 17, naznačen time, da dijelovi glavne okosnice obuhvaćaju hiper-razgranate dijelove Hyp-skupine sljedeće formule:
[image]
u kojoj crtkane linije označavaju priključenje na ostatak molekule i ugljikovi atomi koji su označeni sa zvjezdicama, označavaju S-konfiguraciju.
19. Biorazgradivi hidrogel prema bilo kojem od patentnih zahtjeva 1 do 18, naznačen time, da dijelovi glavne okosnice sadrže najmanje jedan držač razmaka sljedeće formule:
[image]
u kojoj jedna od crtkanih linija označava priključenje na hiper-razgranati dio Hyp-skupine, a druga crtkana linija označava priključenje na ostatak molekule; i
pritom m je cijeli broj od 2 do 4.
20. Biorazgradivi hidrogel prema bilo kojem od patentnih zahtjeva 1 do 19, naznačen time, da dijelovi glavne okosnice sadrže najmanje jedan držač razmaka sljedeće formule:
[image]
u kojoj neoznačena crtkana linija pokazuje priključenje na Hyp;
crtkana linija koja je označena sa zvjezdicom pokazuje vezu između hidrogela i N iz tiosukcinimidne skupine, i
pritom p je cijeli broj od 0 do 10.
21. Biorazgradivi hidrogel prema bilo kojem od patentnih zahtjeva 1 do 20, naznačen time, da su dijelovi glavne okosnice povezani zajedno preko dijelova poprečnog povezivača koji sadrži sljedeću strukturu:
[image]
u kojoj
q je cijeli broj od 3 do 100.
22. Biorazgradivi hidrogel prema bilo kojem od patentnih zahtjeva 1 do 21, naznačen time, da se dijelovi poprečnog povezivača sastoje od PEG koji je simetrično povezan preko esterskih veza na dva alfa, omega-alifatska dikarboksilna držača razmaka koji su omogućeni preko dijelova glavne okosnice spojenih na hiper-razgranati dendritički dio skupine preko permanentnih amidnih veza.
23. Konjugat koji obuhvaća hidrogel prema bilo kojem od patentnih zahtjeva 1 do 22, naznačen time, da je hidrogel sastavljen od dijelova glavne okosnice koji su međupovezani pomoću hidrolitički razgradivih veza i dodatno prenosi permanentne veze do molekula držača razmaka ili blokatorskih skupina ili do njihovih kombinacija.
24. Konjugat koji obuhvaća hidrogel prema bilo kojem od patentnih zahtjeva 1 do 22, naznačen time, da je hidrogel sastavljen od dijelova glavne okosnice koji su međupovezani pomoću hidrolitički razgradivih veza i dodatno prenosi permanentne veze do liganda ili do kelatnih skupina.
25. Konjugat prema patentnom zahtjevu 24, naznačen time, da su ligandi odabrani iz skupine koja se sastoji od sljedećih: 4-aminobenzamidin, 3-(2'-aminobenzhidriloksi)tropan, ε-aminokaproil-p-klorobenzilamid, 1-amino-4-[3-(4,6-diklorotriazin-2-ilamino)-4-sulfofenilamino]antrakinon-2-sulfonska kiselina, 2-(2'-amino-4'-metilfeniltio)-N,N-dimetilbenzilamin-dihidroklorid, angiopoietin-1, aptameri, arotinoidna kiselina, avidin, biotin, kalmodulin, kokaetilen, citosporon B, N,N-diheksil-2-(4-fluorofenil)indol-3-acetamid, N,N-dipropil-2-(4-klorofenil)-6,8-dikloro-imidazo[1,2-a]piridin-3-acetamid, 5-fluoro-2'-deoksiuridin-5'-(p-aminofenil)monofosfat, S-heksil-L-glutation, (S,S)-4-fenil-α-(4-feniloksazolidin-2-iliden)-2-oksazolin-2-acetonitril, Pro-Leu-Gly-hidroksamat, 2-(4-(2-trifluorometil)fenil)piperidin-1-karboksamido)benzojeva kiselina, trimetil(m-aminofenil)amonijev klorid, urokortin III, kofaktori kao adenozin-trifosfat, s-adenozil-metionin, askorbinska kislina, kobalamin, koenzim A, koenzim B, koenzim M, koenzim Q, koenzim F420, citidin-trifosfat, flavin-mononukleotid, flavin-adenin-dinukleotid, glutation, haem, lipoamid, menakvinon, metanofuran, metilkobalamin, molibdopterin, NAD+, NADP+, nukleotidni šećeri, 3'-fosfoadenozin-5'-fosfosulfat, piridoksal-fosfat, polihistidini, pirolokinolin-kvinon, riboflavin, streptavidin, tetrahidrobiopterin, tetrahidrometanopterin, tetrahidrofolna kiselina, biotin-karboksil-nosivi protein (BCCP), vezivni protein kitina, FK506 vezivni proteini (FKBP), FLAG-oznaka, zeleni fluorescentni protein, glutation-S-transferaza, hemagglutinin (HA), vezivni protein maltoze, mik-oznaka, NusA, epitop proteina C, S-oznaka, strep-oznaka, tioredoksini i afinitetni skelni proteini.
26. Konjugat prema patentnom zahtjevu 24, naznačen time, da su kelatne skupine odabrane iz skupine koja se sastoji od sljedećih: 2,2'-bipiridil, 1,2-bis(2-aminofenoksi)etan-N,N,N',N'-tetraoctena kiselina, deferoksamin-mesilat, deferiferikrom, dietilentriamin, 2,3-dimerkapto-1-propanol, dimerkapto-sukcinska kiselina, dimetilglioksin, 2,2'-dipiridil, etilen-diamin, etilendiamintetra (metilenfosfonska kiselina), 1,2-bis(2-amino-5-bromofenoksi)etan-N,N,N'N'-tetraoctena kiselina, 8-hidroksikinolin, iminodiacetat, iminodi(metilfosfonska kiselina), L-mimozin, nitrilotriacetat, oksalat, 1,10-fenantrolin, fitinska kiselina, tartrat, 1,4,7,10-tetraazaciklododekan-1,4,7,10-tetraacetat, N,N,N',N'-tetrakis(2-piridilmetil)etilendiamin, triaminotrietilamin, iminodioctena kiselina, tiourea i 2-pikolilamin.
27. Predlijek povezan s nosačem, naznačen time, da obuhvaća biorazgradivi hidrogel prema bilo kojem od patentnih zahtjeva 1 do 22 kao nosač, pri čemu jedan broj permanentnih veza dijelova glavne okosnice, postoji za svaki tranzijentni povezivač L predlijeka, na kojega je kovalentno priključen biološki aktivni dio skupine D.
28. Predlijek povezan s nosačem prema patentnom zahtjevu 27, naznačen time, da tranzijentna veza između D i L je karbamatna, karbonatna, amidna ili esterska veza.
29. Predlijek povezan s nosačem prema patentnom zahtjevu 27 ili 28, naznačen time, da tranzijentni povezivač L predlijeka obuhvaća dio L1 koji je supstituiran s dijelom L2 i pritom je L2 povezan sa skupinom nosača Z, pri čemu je to hidrogel prema bilo kojem od patentnih zahtjeva 1 do 22.
30. Predlijek povezan s nosačem prema bilo kojem od patentnih zahtjeva 27 do 29, naznačen time, da -L je nebiološki aktivni dio povezivača -L1 koji je predstavljen sljedećom formulom (VI):
[image]
gdje crtkana linija označava priključenje na primarnu ili sekundarnu amino skupinu od biološki aktivnog dijela skupine D koji sadrži amin, pomoću stvaranja amidne veze; i pritom X, X1, X2, R1, R1a, R2, R2a, R3 i R3a iz formule (VI), imaju sljedeće značenje:
X je C(R4R4a); N(R4); O; C(R4R4a)-C(R5R5a); C(R5R5a)-C(R4R4a); C(R4R4a)-N(R6);
N(R6)-C(R4R4a); C(R4R4a)-O; ili O-C(R4R4a);
X1 je C; ili S(O);
X2 je C(R7, R7a); ili C(R7, R7a)-C(R8, R8a);
R1, R1a, R2, R2a, R3, R3a, R4, R4a, R5, R5a, R6, R7, R7a, R8, R8asu neovisno odabrani iz skupine koja se sastoji od H; i C1-4-alkila;
prema potrebi, jedan ili više od parova R1a/R4a, R1a/R5a, R4a/R5a, R7a/R8a, tvore kemijsku vezu;
prema potrebi su jedan ili više od parova R1/R1a, R2/R2a, R4/R4a, R5/R5a, R7/R7a, R8/R8a spojeni zajedno s atomom na kojega su priključeni, za tvorbu C3-7-cikloalkila; ili 4-7-članog heterociklila;
prema potrebi su jedan ili više od parova R1/R4, R1/R5, R1/R6, R4/R5, R7/R8, R2/R3 spojeni zajedno s atomima na koje su priključeni, za tvorbu prstena A;
prema potrebi su R3/R3a spojeni zajedno s dušikovim atomom na kojega su priključeni, za tvorbu 4-7-člang heterocikla;
A je odabran iz skupine koja se sastoji od sljedećih: fenil; naftil; indenil; indanil; tetralinil; C3-10-cikloalkil; 4-7-člani heterociklil; i 9-11-člani heterobiciklil; i
pritom je L1 supstituiran s jednom skupinom L2-Z te je prema potrebi dodatno supstituiran, uz uvjet da vodik koji je označen sa zvjezdicom u formuli (VI), nije zamijenjen supstituentom;
pri čemu
L2 je jednostruka kemijska veza ili držač razmaka; i
Z je odgovarajući hidrogel prema bilo kojem od patentnih zahtjeva 1 do 21.
31. Predlijek povezan s nosačem prema bilo kojem od patentnih zahtjeva 27 do 30, naznačen time, da je biološki aktivni dio skupine odabran iz skupine koja se sastoji od polipeptida, proteina, oligonukleotida te biološki aktivnih ostataka male molekule.
32. Predlijek povezan s nosačem prema bilo kojem od patentnih zahtjeva 27 do 31, naznačen time, da je L2 priključen na Z preko terminalne skupine koja ima sljedeću strukturu:
[image]
gdje crtkane linije označavaju odgovarajuće priključenje na L2 odnosno Z.
33. Farmaceutski pripravak, naznačen time, da obuhvaća predlijek prema bilo kojem od patentnih tzahtjeva 27 do 32 ili njegovu farmaceutski prihvatljivu sol, zajedno s farmaceutski prihvatljivim pomoćnim sredstvom.
34. Predlijek prema bilo kojem od patentnih zahtjeva 27 do 32, ili farmaceutski pripravak prema patentnom zahtjevu 33, naznačen time, da se upotrebljava kao medikament.
35. Postupak za proizvodnju hidrogela, naznačen time, da obuhvaća sljedeći korak:
(a) reakciju reagensa glavne okosnice koji ima sljedeću formulu:
[image]
u kojoj je n cijeli broj od 3 do 100;
s reagensom poprečnog povezivača sljedeće formule:
[image]
pri čemu
q je cijeli broj od 3 do 100:
svaki m neovisno predstavlja cijeli broj od 2 do 4;
u odnosu amin/aktivni ester u iznosu od 2:1 do 1,05:1, koji rezultira u opterećenju hidrogela od 0,02 do 2 mmol amina po gramu hidrogela;
te time, da se reagensi rastapaju u aprotičkom otapalu u prisutnosti prikladne lužine.
36. Hidrogel, naznačen time, da se može dobiti putem postupka prema patentnom zahtjevu 35.
37. Hidrogel prema bilo kojem od patentnih zahtjeva 1 do 21 ili 36, naznačen time, da se nalazi u obliku obloge, prepleta, stenta ili mikročestica koje se dobivaju pomoću usitnjavanja putem mehaničkih postupaka kao što su miješanje, drobljenje, rezanje stlačivanjem ili mljevenje, te prema potrebi prosijavanje.
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WO2011089215A1 (en) | 2010-01-22 | 2011-07-28 | Ascendis Pharma As | Dipeptide-based prodrug linkers for aromatic amine-containing drugs |
WO2011089214A1 (en) | 2010-01-22 | 2011-07-28 | Ascendis Pharma As | Carrier-linked carbamate prodrug linkers |
DK2525830T3 (en) | 2010-01-22 | 2016-08-15 | Ascendis Pharma As | DIPEPTID-BASED PRODRUG LINKERS TO ALIFATIC AMINE-CONTAINING MEDICINES |
US9850296B2 (en) | 2010-08-10 | 2017-12-26 | Ecole Polytechnique Federale De Lausanne (Epfl) | Erythrocyte-binding therapeutics |
JP6017422B2 (ja) | 2010-08-10 | 2016-11-02 | エコール・ポリテクニーク・フェデラル・ドゥ・ローザンヌ(ウペエフエル)Ecole Polytechnique Federale de Lausanne (EPFL) | 赤血球結合療法 |
US9517257B2 (en) | 2010-08-10 | 2016-12-13 | Ecole Polytechnique Federale De Lausanne (Epfl) | Erythrocyte-binding therapeutics |
EP2438930A1 (en) | 2010-09-17 | 2012-04-11 | Sanofi-Aventis Deutschland GmbH | Prodrugs comprising an exendin linker conjugate |
US10451897B2 (en) | 2011-03-18 | 2019-10-22 | Johnson & Johnson Vision Care, Inc. | Components with multiple energization elements for biomedical devices |
CA2831340A1 (en) * | 2011-05-03 | 2012-11-08 | Robert T. Lum | Excipient compatibility with ezatiostat |
EP2723357A4 (en) * | 2011-06-21 | 2015-04-01 | Bvw Holding Ag | MEDICAL DEVICE COMPRISING BOSWELLIC ACID |
MX349950B (es) * | 2011-08-12 | 2017-08-22 | Ascendis Pharma As | Profarmacos de treprostinil enlazados a un portador. |
EP3643306A3 (en) | 2011-08-12 | 2020-08-26 | Ascendis Pharma A/S | Carrier-linked prodrugs having reversible carboxylic ester linkages |
CN103874480A (zh) | 2011-08-12 | 2014-06-18 | 阿森迪斯药物股份有限公司 | 前列环素的缓释组合物 |
US20150010634A1 (en) | 2011-10-12 | 2015-01-08 | Ascendis Pharma Ophthamology Division A/S | Prevention and treatment of ocular conditions |
KR20150000464A (ko) * | 2011-11-03 | 2015-01-02 | 바이엘 인텔렉쳐 프로퍼티 게엠베하 | 펩티드의 방출가능한 연결을 위한 티로신 기재의 링커 |
US8857983B2 (en) | 2012-01-26 | 2014-10-14 | Johnson & Johnson Vision Care, Inc. | Ophthalmic lens assembly having an integrated antenna structure |
CA2868925C (en) | 2012-04-25 | 2020-01-21 | Ascendis Pharma A/S | Prodrugs of hydroxyl-comprising drugs |
US20140073589A1 (en) * | 2012-06-27 | 2014-03-13 | Shire Ag | Amphetamine Prodrugs |
PT2888258T (pt) * | 2012-08-21 | 2019-08-21 | Janssen Pharmaceutica Nv | Hapteno de paliperidona |
PT3321254T (pt) | 2012-08-21 | 2020-10-20 | Janssen Pharmaceutica Nv | Haptenos de aripiprazol e seu uso em imunoensaios |
EP2888284B1 (en) | 2012-08-21 | 2022-07-06 | Janssen Pharmaceutica NV | Antibodies to risperidone haptens and use thereof |
AU2013305938B2 (en) | 2012-08-21 | 2017-08-17 | Saladax Biomedical Inc. | Antibodies to paliperidone haptens and use thereof |
PL3462173T3 (pl) | 2012-08-21 | 2021-08-16 | Janssen Pharmaceutica Nv | Przeciwciała przeciwko rysperydonowi i ich zastosowanie |
PL3354751T3 (pl) | 2012-08-21 | 2020-03-31 | Janssen Pharmaceutica Nv | Przeciwciała dla arypiprazolu i ich zastosowanie |
AU2013305965B2 (en) | 2012-08-21 | 2017-08-24 | Saladax Biomedical Inc. | Antibodies to paliperidone and use thereof |
JP6389176B2 (ja) | 2012-08-21 | 2018-09-12 | ヤンセン ファーマシューティカ エヌ.ベー. | アリピプラゾールハプテンに対する抗体及びその使用 |
US10980860B2 (en) * | 2012-10-11 | 2021-04-20 | Ascendis Pharma A/S | Diagnosis, prevention and treatment of diseases of the joint |
AU2013328785B2 (en) | 2012-10-11 | 2016-07-21 | Ascendis Pharma A/S | Hydrogel prodrugs |
WO2014056923A1 (en) * | 2012-10-11 | 2014-04-17 | Ascendis Pharma Ophthalmology Division A/S | Vegf neutralizing prodrugs for the treatment of ocular conditions |
JP6290243B2 (ja) | 2012-12-07 | 2018-03-07 | アセンディス ファーマ エー/エス | 担体連結プロスタノイドプロドラッグ |
US20140271885A1 (en) * | 2013-03-15 | 2014-09-18 | Intezyne Technologies, Inc. | Copolymers for stable micelle formulations |
DK2988732T3 (da) * | 2013-04-22 | 2023-06-26 | Ascendis Pharma As | Modificerede hydrogeler |
EP2988783A1 (en) | 2013-04-22 | 2016-03-02 | Ascendis Pharma A/S | Hydrogel-linked prodrugs releasing modified drugs |
EP3010486B1 (en) | 2013-06-19 | 2023-11-22 | The Regents of The University of California | Chemical structures for localized delivery of therapeutic agents |
RU2543375C1 (ru) * | 2013-07-29 | 2015-02-27 | Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Башкирский государственный университет" | Комплексное соединение производного метилурацила с органической кислотой и способ его получения |
WO2015023675A2 (en) | 2013-08-12 | 2015-02-19 | Pharmaceutical Manufacturing Research Services, Inc. | Extruded immediate release abuse deterrent pill |
BR112016007371A2 (pt) | 2013-10-01 | 2017-08-01 | Glaxosmithkline Ip Dev Ltd | compostos para cromatografia por afinidade e para extensão da meia-vida de um agente terapêutico |
US20180042996A1 (en) * | 2013-10-08 | 2018-02-15 | Ascendis Pharma Osteoarthritis Division A/S | Hydrogel-Linked IL-1ra Prodrug |
CN103554296B (zh) * | 2013-10-12 | 2015-09-16 | 天津大学 | 一种亚油酸改性葡聚糖及制备高分子脂质体的方法 |
CA2929201A1 (en) | 2013-11-11 | 2015-05-14 | Ascendis Pharma Relaxin Division A/S | Relaxin prodrugs |
US9675607B2 (en) * | 2013-11-13 | 2017-06-13 | Northwestern University | Epimorphic regeneration and related hydrogel delivery systems |
CN103706233A (zh) * | 2013-12-17 | 2014-04-09 | 杨亮月 | 一种环氧乙烷零排放处理体系及方法 |
US9492444B2 (en) | 2013-12-17 | 2016-11-15 | Pharmaceutical Manufacturing Research Services, Inc. | Extruded extended release abuse deterrent pill |
WO2015095391A1 (en) | 2013-12-17 | 2015-06-25 | Pharmaceutical Manufacturing Research Services, Inc. | Extruded extended release abuse deterrent pill |
US10046056B2 (en) | 2014-02-21 | 2018-08-14 | École Polytechnique Fédérale De Lausanne (Epfl) | Glycotargeting therapeutics |
US10946079B2 (en) | 2014-02-21 | 2021-03-16 | Ecole Polytechnique Federale De Lausanne | Glycotargeting therapeutics |
NZ723879A (en) | 2014-02-21 | 2018-03-23 | Ecole Polytechnique Fed Lausanne Epfl | Glycotargeting therapeutics |
US10953101B2 (en) | 2014-02-21 | 2021-03-23 | École Polytechnique Fédérale De Lausanne (Epfl) | Glycotargeting therapeutics |
AU2015229014B2 (en) * | 2014-03-14 | 2019-07-25 | The Regents Of The University Of California | TCO conjugates and methods for delivery of therapeutic agents |
CN106714854B (zh) | 2014-07-17 | 2020-09-04 | 加利福尼亚大学董事会 | 用于生物医学应用的可控的自退火微凝胶颗粒 |
EP3169315B1 (en) | 2014-07-17 | 2020-06-24 | Pharmaceutical Manufacturing Research Services, Inc. | Immediate release abuse deterrent liquid fill dosage form |
CA2955569C (en) | 2014-08-06 | 2023-02-14 | Ascendis Pharma A/S | Prodrugs comprising an aminoalkyl glycine linker |
US9599842B2 (en) | 2014-08-21 | 2017-03-21 | Johnson & Johnson Vision Care, Inc. | Device and methods for sealing and encapsulation for biocompatible energization elements |
US9383593B2 (en) | 2014-08-21 | 2016-07-05 | Johnson & Johnson Vision Care, Inc. | Methods to form biocompatible energization elements for biomedical devices comprising laminates and placed separators |
US10381687B2 (en) | 2014-08-21 | 2019-08-13 | Johnson & Johnson Vision Care, Inc. | Methods of forming biocompatible rechargable energization elements for biomedical devices |
US9923177B2 (en) * | 2014-08-21 | 2018-03-20 | Johnson & Johnson Vision Care, Inc. | Biocompatibility of biomedical energization elements |
US10361405B2 (en) | 2014-08-21 | 2019-07-23 | Johnson & Johnson Vision Care, Inc. | Biomedical energization elements with polymer electrolytes |
US9793536B2 (en) | 2014-08-21 | 2017-10-17 | Johnson & Johnson Vision Care, Inc. | Pellet form cathode for use in a biocompatible battery |
US10627651B2 (en) | 2014-08-21 | 2020-04-21 | Johnson & Johnson Vision Care, Inc. | Methods and apparatus to form biocompatible energization primary elements for biomedical devices with electroless sealing layers |
US9715130B2 (en) | 2014-08-21 | 2017-07-25 | Johnson & Johnson Vision Care, Inc. | Methods and apparatus to form separators for biocompatible energization elements for biomedical devices |
US10361404B2 (en) | 2014-08-21 | 2019-07-23 | Johnson & Johnson Vision Care, Inc. | Anodes for use in biocompatible energization elements |
US9941547B2 (en) | 2014-08-21 | 2018-04-10 | Johnson & Johnson Vision Care, Inc. | Biomedical energization elements with polymer electrolytes and cavity structures |
EP3209282A4 (en) | 2014-10-20 | 2018-05-23 | Pharmaceutical Manufacturing Research Services, Inc. | Extended release abuse deterrent liquid fill dosage form |
WO2016063959A1 (ja) | 2014-10-24 | 2016-04-28 | 日油株式会社 | 環状ベンジリデンアセタールリンカーを有する抗体―薬物複合体 |
US11298427B2 (en) | 2015-05-29 | 2022-04-12 | Ascendis Pharma A/S | Prodrugs comprising a pyroglutamate linker |
CA2992602A1 (en) | 2015-09-23 | 2017-03-30 | Genentech, Inc. | Optimized variants of anti-vegf antibodies |
US11458041B2 (en) * | 2015-10-08 | 2022-10-04 | Ocular Therapeutix, Inc. | Punctal plug and bioadhesives |
US20170136144A1 (en) | 2015-11-12 | 2017-05-18 | John C. Herr | Compositions and methods for vas-occlusive contraception |
CA3008809A1 (en) | 2015-12-17 | 2017-06-22 | Janssen Pharmaceutica Nv | Antibodies to risperidone and use thereof |
WO2017101883A1 (zh) * | 2015-12-18 | 2017-06-22 | 韩捷 | 一种可在生理条件下降解的水凝胶 |
WO2017112704A1 (en) | 2015-12-23 | 2017-06-29 | Viking Scientific, Inc. | Hydrogel prodrug for treatment |
WO2017142879A1 (en) | 2016-02-16 | 2017-08-24 | The Regents Of The University Of California | Methods for immune system modulation with microporous annealed particle gels |
US10345620B2 (en) | 2016-02-18 | 2019-07-09 | Johnson & Johnson Vision Care, Inc. | Methods and apparatus to form biocompatible energization elements incorporating fuel cells for biomedical devices |
MX2018009938A (es) | 2016-03-01 | 2019-03-14 | Ascendis Pharma Bone Diseases As | Profarmacos de hormona paratiroidea (pth). |
EP3439670A4 (en) | 2016-04-08 | 2019-11-27 | The Regents of the University of California | MODIFIED HYALURONIC ACID HYGELS AND PROTEINS FOR THE TEMPORARY RELEASE OF BIOLOGICAL ACTIVE SUBSTANCES |
CN105963792B (zh) * | 2016-04-29 | 2019-03-22 | 深圳迈普再生医学科技有限公司 | 医用水凝胶组合物,医用水凝胶及其制备方法与应用 |
US11896671B2 (en) | 2016-07-13 | 2024-02-13 | Ascendis Pharma A/S | Conjugation method for carrier-linked prodrugs |
AU2017336250C1 (en) | 2016-09-29 | 2023-08-03 | Ascendis Pharma Bone Diseases A/S | Incremental dose finding in controlled-release PTH compounds |
CN117257922A (zh) | 2016-09-29 | 2023-12-22 | 阿森迪斯药物骨疾病股份有限公司 | 具有低峰-谷比的pth化合物 |
IL290054B2 (en) | 2016-09-29 | 2024-03-01 | Ascendis Pharma Growth Disorders As | Combined treatment with CNP agonists with controlled release |
CN117838873A (zh) | 2016-09-29 | 2024-04-09 | 阿森迪斯药物骨疾病股份有限公司 | 控释pth化合物的剂量方案 |
EP3562523A4 (en) | 2016-12-29 | 2020-09-30 | Tempo Therapeutics, Inc. | PROCESSES AND SYSTEMS FOR THE TREATMENT OF A MEDICAL IMPLANT SITE |
PT3592392T (pt) | 2017-03-10 | 2023-11-23 | Georgia Tech Res Inst | Biomateriais manipulados por fasl com função imunomoduladora |
TW201842936A (zh) | 2017-03-22 | 2018-12-16 | 美商建南德克公司 | 水凝膠交聯化的玻尿酸前藥組合物及方法 |
JOP20190245A1 (ar) * | 2017-04-20 | 2019-10-15 | Novartis Ag | أنظمة توصيل إطلاق مستدام تتضمن روابط بلا أثر لنقطة الربط |
CN108864258A (zh) * | 2017-05-12 | 2018-11-23 | 北京康明海慧生物科技有限公司 | 具有抑制肿瘤功能的peg化多肽及其制备方法与应用 |
WO2018232176A1 (en) | 2017-06-16 | 2018-12-20 | The University Of Chicago | Compositions and methods for inducing immune tolerance |
CN107583104B (zh) * | 2017-10-31 | 2020-12-01 | 无锡中科光远生物材料有限公司 | 一种可注射的用于脊柱修复的凝胶材料 |
BR112020008631A2 (pt) * | 2017-11-02 | 2020-10-20 | Tarsius Pharma Ltd. | conjugado de fosforilcolina-tuftsina para tratamento de inflamação ocular |
CN107880288A (zh) * | 2017-11-29 | 2018-04-06 | 桂林华诺威生物科技有限公司 | 一种透明质酸钠凝胶的制备方法 |
CN108096630B (zh) * | 2018-01-29 | 2020-09-04 | 暨南大学 | 一种载淫羊藿苷和去铁胺的聚乳酸基骨组织支架及制备方法和应用 |
MX2020009857A (es) | 2018-03-28 | 2021-01-08 | Ascendis Pharma Oncology Div A/S | Conjugados de interleucina-2 (il-2). |
FR3079421A1 (fr) * | 2018-03-28 | 2019-10-04 | Edix Sa | Presentations injectables, seringues et compositions a liberation prolongee et/ou controlee de lanreotide |
CN110865130B (zh) * | 2018-08-27 | 2023-08-22 | 北京海晶生物医药科技有限公司 | 一种盐酸奥洛他定及其有关物质的检测方法 |
SG11202101971XA (en) | 2018-09-26 | 2021-03-30 | Ascendis Pharma As | Novel hydrogel conjugates |
TW202027794A (zh) * | 2018-10-03 | 2020-08-01 | 瑞士商諾華公司 | 血管生成素樣3多肽之持續遞送 |
CN111077235B (zh) * | 2018-10-19 | 2023-09-08 | 重庆医药工业研究院有限责任公司 | 一种测定2-[(2-甲基-5-溴苯基)甲基]-5-(4-氟苯基)噻吩杂质的方法 |
JP2022516314A (ja) | 2019-01-04 | 2022-02-25 | アセンディス ファーマ オンコロジー ディヴィジョン エー/エス | 自然免疫アゴニストのための持続性局所性薬物レベル |
BR112021011592A2 (pt) | 2019-01-04 | 2021-10-26 | Ascendis Pharma Oncology Division A/S | Conjugados de agonistas de receptor de reconhecimento de padrão |
EP3906018A1 (en) | 2019-01-04 | 2021-11-10 | Ascendis Pharma Oncology Division A/S | Induction of sustained local inflammation |
US20220054478A1 (en) | 2019-01-04 | 2022-02-24 | Ascendis Pharma Oncology Division A/S | Minimization of systemic inflammation |
US11471497B1 (en) | 2019-03-13 | 2022-10-18 | David Gordon Bermudes | Copper chelation therapeutics |
IL295911A (en) * | 2019-06-07 | 2022-10-01 | Likarda Llc | Targetable microparticle dissolution of hydrogels |
WO2020254612A1 (en) | 2019-06-21 | 2020-12-24 | Ascendis Pharma Oncology Division A/S | Controlled-release tyrosine kinase inhibitor compounds with localized pd properties |
WO2020254617A1 (en) | 2019-06-21 | 2020-12-24 | Ascendis Pharma Oncology Division A/S | Anti-ctla4 compounds with localized pk properties |
AU2020295724A1 (en) | 2019-06-21 | 2021-12-02 | Ascendis Pharma Oncology Division A/S | Tyrosine kinase inhibitor conjugates |
CN114026080A (zh) | 2019-06-21 | 2022-02-08 | 阿森迪斯药物股份有限公司 | 含有提供π-电子对的杂芳族氮的化合物的缀合物 |
EP3986471A1 (en) | 2019-06-21 | 2022-04-27 | Ascendis Pharma A/S | Conjugates of an electron-donating nitrogen or tertiary amine comprising compounds |
WO2020254607A1 (en) | 2019-06-21 | 2020-12-24 | Ascendis Pharma Oncology Division A/S | Anti-ctla4 compounds with localized pd properties |
WO2020254606A1 (en) | 2019-06-21 | 2020-12-24 | Ascendis Pharma A/S | Conjugates of heteroaromatic nitrogen-comprising compounds |
WO2020254613A1 (en) | 2019-06-21 | 2020-12-24 | Ascendis Pharma Oncology Division A/S | Controlled-release tyrosine kinase inhibitor compounds with localized pk properties |
US20220305136A1 (en) | 2019-06-21 | 2022-09-29 | Ascendis Pharma Oncology Division A/S | Anti-ctla4 conjugates |
KR102658962B1 (ko) * | 2019-06-26 | 2024-04-23 | 주식회사 바이오오케스트라 | 미셀 나노입자 및 이의 용도 |
CA3145024A1 (en) * | 2019-07-03 | 2021-01-07 | Molly Sandra Shoichet | Hydrogel compositions and uses thereof |
CN112168820B (zh) * | 2019-07-05 | 2023-09-29 | 中国科学院生物物理研究所 | SRCAP ATPase抑制剂在结直肠癌治疗中的应用 |
EP4021951A1 (en) * | 2019-08-29 | 2022-07-06 | Paul Douglas Godfrin | Hydrogels as oral delivery dosage forms, methods of making and using same |
TW202128141A (zh) * | 2019-11-19 | 2021-08-01 | 美商盧伯利索先進材料有限公司 | 用雙縮二胍鹽化之聚胺酯組成物 |
IL294327A (en) | 2020-01-03 | 2022-08-01 | Ascendis Pharma As | Conjugates undergoing intramolecular rearrangements |
CN111138293B (zh) * | 2020-01-10 | 2023-07-07 | 蚌埠丰原医药科技发展有限公司 | 一种用微通道反应器合成富马酸伊布利特中间体的方法 |
KR20220151622A (ko) | 2020-02-06 | 2022-11-15 | 오큘라 테라퓨틱스, 인코포레이티드 | 안질환 치료를 위한 조성물 및 방법 |
KR102375663B1 (ko) * | 2020-03-24 | 2022-03-16 | 재단법인대구경북과학기술원 | 무손실 세포 염색 방법 및 장치 |
KR20220157462A (ko) | 2020-03-25 | 2022-11-29 | 오큘라 테라퓨틱스, 인코포레이티드 | 티로신 키나제 억제제를 함유하는 안구 임플란트 |
AU2021269007A1 (en) | 2020-05-04 | 2022-11-24 | Ascendis Pharma A/S | Hydrogel irradiation |
CN113694261B (zh) * | 2020-05-21 | 2022-09-09 | 江苏百赛飞生物科技有限公司 | 一种抗菌复合涂层及其制备方法和制品 |
WO2021243309A1 (en) * | 2020-05-28 | 2021-12-02 | Sollievo Pharmaceuticals, Inc | Parenteral delivery of avizafone |
AU2021286177A1 (en) | 2020-06-03 | 2022-12-01 | Ascendis Pharma Oncology Division A/S | IL-2 sequences and uses thereof |
US11739166B2 (en) | 2020-07-02 | 2023-08-29 | Davol Inc. | Reactive polysaccharide-based hemostatic agent |
CA3184998A1 (en) | 2020-08-05 | 2022-02-10 | Samuel WEISBROD | Conjugates comprising reversible linkers and uses thereof |
KR20230057447A (ko) | 2020-08-28 | 2023-04-28 | 아센디스 파마 온콜로지 디비전 에이/에스 | 글리코실화된 il-2 단백질 및 이의 용도 |
AU2021349316A1 (en) | 2020-09-28 | 2023-04-27 | Ascendis Pharma Bone Diseases A/S | Improvement of physical and mental well-being of patients with hypoparathyroidism |
CN112316156B (zh) * | 2020-10-27 | 2022-03-15 | 四川大学 | 具抗氧化和抗菌性的胶原蛋白修复膜、其制备方法及应用 |
KR102437315B1 (ko) * | 2020-11-02 | 2022-08-30 | 아주대학교산학협력단 | 하이브리드 하이드로겔 및 이의 생의학적 용도 |
MX2023011059A (es) | 2021-04-01 | 2023-09-29 | Ascendis Pharma As | Uso de hormona del crecimiento de accion prolongada para tratamiento de enfermedades inducidas por inflamacion. |
CN113304139B (zh) * | 2021-06-30 | 2022-04-29 | 贵州医科大学 | Viniferifuran在制备黄嘌呤氧化酶抑制药物中的应用 |
CN113398145B (zh) * | 2021-07-02 | 2022-10-14 | 合肥康诺生物制药有限公司 | 含nad与氨氯地平的药物组合物及其用途 |
CN113461979A (zh) * | 2021-07-19 | 2021-10-01 | 吉林大学 | 一种通过血红蛋白催化交联的仿贻贝类水凝胶的制备方法 |
WO2023110727A2 (en) | 2021-12-13 | 2023-06-22 | Ascendis Pharma Oncology Division A/S | Novel cancer treatments with tlr7/8 agonists |
CN114469926B (zh) * | 2022-01-28 | 2023-06-27 | 吉林省健维天然生物科技有限公司 | 二氢槲皮素的新用途及二氢槲皮素水凝胶的制备方法 |
CN115109275B (zh) * | 2022-08-29 | 2022-11-01 | 杭州艾名医学科技有限公司 | 一种动态交联可降解水凝胶、制备方法及应用 |
CN115444840B (zh) * | 2022-09-15 | 2023-08-25 | 四川大学 | 一种前药、两性离子水凝胶及其制备方法、应用 |
CN115322397B (zh) * | 2022-09-23 | 2024-04-30 | 福州大学 | 一种预防术后腹腔粘连的两性离子水凝胶及其制备方法 |
CN115537017B (zh) * | 2022-09-27 | 2023-09-01 | 四川大学 | 一种水凝胶及其制备方法和应用 |
WO2024094673A1 (en) | 2022-11-02 | 2024-05-10 | Ascendis Pharma Bone Diseases A/S | Pth treatment regimen comprising two pth compounds |
Family Cites Families (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK0627911T3 (da) | 1992-02-28 | 2000-11-20 | Univ Texas | Fotopolymeriserbare bionedbrydelige hydrogeler somvævskontaktmaterialer og bærere med reguleret frigivelse |
US20020064546A1 (en) * | 1996-09-13 | 2002-05-30 | J. Milton Harris | Degradable poly(ethylene glycol) hydrogels with controlled half-life and precursors therefor |
UA72189C2 (uk) * | 1997-11-17 | 2005-02-15 | Янссен Фармацевтика Н.В. | Фармацевтична композиція, що містить водну суспензію субмікронних ефірів 9-гідроксирисперидон жирних кислот |
US6624142B2 (en) | 1997-12-30 | 2003-09-23 | Enzon, Inc. | Trimethyl lock based tetrapartate prodrugs |
US6348558B1 (en) | 1999-12-10 | 2002-02-19 | Shearwater Corporation | Hydrolytically degradable polymers and hydrogels made therefrom |
US6413507B1 (en) | 1999-12-23 | 2002-07-02 | Shearwater Corporation | Hydrolytically degradable carbamate derivatives of poly (ethylene glycol) |
US20050260259A1 (en) * | 2004-04-23 | 2005-11-24 | Bolotin Elijah M | Compositions for treatment with glucagon-like peptide, and methods of making and using the same |
US7393953B2 (en) | 2002-04-04 | 2008-07-01 | Enzon, Inc. | Polymeric acyl derivatives of indoles |
CA2513483C (en) * | 2003-01-17 | 2011-11-29 | Cornell Research Foundation, Inc. | Injectable hydrogel microspheres from aqueous two-phase system |
PL1620118T3 (pl) | 2003-04-08 | 2014-11-28 | Yeda Res & Dev | Leki odwracalnie pegylowane |
WO2005000360A2 (en) | 2003-05-23 | 2005-01-06 | Nektar Therapeutics Al, Corporation | Peg derivatives having an amidocarbonate linkage |
MXPA06010782A (es) * | 2004-03-23 | 2007-03-28 | Complex Biosystems Gmbh | Ligador de profarmaco. |
US7968085B2 (en) * | 2004-07-05 | 2011-06-28 | Ascendis Pharma A/S | Hydrogel formulations |
DE102004051715A1 (de) | 2004-10-23 | 2005-06-30 | Clariant Gmbh | Flüssigwaschmittel enthaltend Farbfixiermittel |
KR100665672B1 (ko) | 2005-04-13 | 2007-01-09 | 성균관대학교산학협력단 | 새로운 온도 및 pH 민감성 블록 공중합체 및 이를 이용한고분자 하이드로겔 |
GB2427360A (en) | 2005-06-22 | 2006-12-27 | Complex Biosystems Gmbh | Aliphatic prodrug linker |
JP2009523494A (ja) | 2006-01-12 | 2009-06-25 | ヒストジェニックス コーポレイション | 破壊された靱帯又は腱の修復及び再構築のための、及び靱帯及び腱の損傷の処置のための方法 |
WO2008034122A2 (en) | 2006-09-15 | 2008-03-20 | Enzon Pharmaceuticals, Inc. | Hindered ester-based biodegradable linkers for oligonucleotide delivery |
GB0619175D0 (en) * | 2006-09-29 | 2006-11-08 | Univ Nottingham | Polymer |
JP5539725B2 (ja) * | 2006-11-27 | 2014-07-02 | アクタマックス サージカル マテリアルズ リミテッド ライアビリティ カンパニー | 分岐末端反応物及びそれから製造されるポリマーヒドロゲル組織接着剤 |
JP2010519183A (ja) * | 2007-02-06 | 2010-06-03 | インセプト エルエルシー | 生理溶液の溶出のためのタンパク質の沈殿を用いる重合 |
US20080220047A1 (en) * | 2007-03-05 | 2008-09-11 | Sawhney Amarpreet S | Low-swelling biocompatible hydrogels |
US8961947B2 (en) | 2007-04-13 | 2015-02-24 | Kuros Biosurgery Ag | Polymeric tissue sealant |
LT2237799T (lt) | 2008-02-01 | 2019-07-25 | Ascendis Pharma A/S | Provaistas, apimantis besiskaidantį linkerį |
CN103550847A (zh) * | 2008-04-28 | 2014-02-05 | 佐吉尼克斯股份有限公司 | 用于治疗偏头痛的新制剂 |
KR101756493B1 (ko) * | 2009-10-29 | 2017-07-10 | 아센디스 파마 에이에스 | 생분해성 하이드로겔의 살균 |
EP2438930A1 (en) * | 2010-09-17 | 2012-04-11 | Sanofi-Aventis Deutschland GmbH | Prodrugs comprising an exendin linker conjugate |
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