DK3139961T3 - Hydrogeler af methacryl-hyaluronsyrederivater til oral enzymterapi ved cøliaki - Google Patents
Hydrogeler af methacryl-hyaluronsyrederivater til oral enzymterapi ved cøliaki Download PDFInfo
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- DK3139961T3 DK3139961T3 DK15725516.7T DK15725516T DK3139961T3 DK 3139961 T3 DK3139961 T3 DK 3139961T3 DK 15725516 T DK15725516 T DK 15725516T DK 3139961 T3 DK3139961 T3 DK 3139961T3
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- Prior art keywords
- eda
- pep
- hyaluronic acid
- enzyme
- hydrogels
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Classifications
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- 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
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
- C08B37/0063—Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
- C08B37/0072—Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates
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- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/24—Crosslinking, e.g. vulcanising, of macromolecules
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- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/28—Treatment by wave energy or particle radiation
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- C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
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- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21026—Prolyl oligopeptidase (3.4.21.26), i.e. proline-specific endopeptidase
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- C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
- C08J2305/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
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Claims (11)
1. Sammensætning omfattende mindst et eksogent enzym, hvilket enzym er udvalgt fra gruppen bestående af prolylendopeptidase (PEP), endoprotease (EP) og kombinationer deraf, hvilket enzym er indesluttet i en hydrogel af foto-tværbundne methacryl-hyaluronsyre-derivater (HA-EDA-MA), hvor hyaluron-syre-derivaterne omfatter hyaluronsyre (HA) eller et salt deraf med en molekylvægt på mellem 50.000 og 1.500.000 dalton, hvor mindst en hydroxyl-gruppe efter aktivering med et carboniseringsmiddel valgt blandt carbonhol-dige phenylestere eller haloform-phenylestere er blevet funktionaliseret ved omsætning med ethylendiamin (EDA) og efterfølgende omsætning med methacrylsyreanhydrid (MA).
2. Sammensætning ifølge krav 1, hvor enzymet er indesluttet i hydrogelen i en koncentration på mellem 1 mU/mg og 100U/mg polymer.
3. Sammensætning ifølge et hvilket som helst af kravene 1-2, hvilken sammensætning er i gelform.
4. Sammensætning ifølge et hvilket som helst af kravene 1-2, hvilken sammensætning er i form af frysetørret pulver.
5. Sammensætning ifølge krav 4, yderligere omfattende mindst et cryobeskyt-tende stof i en koncentration på mellem 0,1 og 10 % w/w i forhold til vægten af polymeren; hvilket cryobeskyttende stof fortrinsvis er trehalose.
6. Sammensætning ifølge et hvilket som helst af kravene 1-5, hvor enzymet, når det er en PEP, er afledt af en mikroorganisme udvalgt fra gruppen bestående af Flavobacterium meningosepticum (FM), Myxococcus xanthus (MX), Sphingomonas capsulata (SC) eller Aspergillus niger (AN) eller kombinationer deraf, når det er en EP, er en byg-endoprotease.
7. Sammensætning ifølge et hvilket som helst af kravene 1-6, til anvendelse ved behandling af cøliaki.
8. Farmaceutisk formulering til oral indgivelse, hvilken formulering omfatter en sammensætning ifølge et hvilket som helst af kravene 1-6.
9. Fremgangsmåde til fremstilling af en sammensætning ifølge et hvilket som helst af kravene 1-6, hvilken fremgangsmåde omfatter fototværbinding af HA-EDA-MA-derivater, ved hjælp af fotobestråling ved en bølgelængde i området 180-800 nm, i vandig opløsning ved en koncentration mellem 1 % w/v og 20 % w/v, hvor fototværbindingen udføres i nærvær af mindst et eksogent enzym i en koncentration på mellem 1 mU/mg og 100U/mg polymer; eller hvor fototværbindingen udføres i fravær af det eksogene enzym, som derefter tilføres ved at bringe de opnåede hydrogeler i kontakt med en opløsning af eksogent enzym i en koncentration på mellem 1 mU/mg og 100U/mg polymer; hvor enzymet er udvalgt fra gruppen bestående af prolylendopeptidase (PEP), endoprotease (EP) og kombinationer deraf; hvor FIA-EDA-MA-derivaterne omfatter hyaluronsyre (HA) eller et salt deraf med en molekylvægt på mellem 50.000 og 1.500.000 dalton, hvor mindst en hydroxylgruppe er blevet funktionaliseret ved omsætning med ethylendiamin (EDA) og efterfølgende omsætning med methacrylsyreanhydrid (MA).
10. Fremgangsmåde ifølge krav 9, omfattende fremstilling af FIA-EDA-MA-de-rivater i henhold til følgende trin: (a) at bringe et hyaluronsyre (FIA)-salt i polært aprotisk opløsningsmiddel i kontakt med et carboniseringsmiddel valgt blandt carbonholdige phenylestere eller haloform-phenylestere til opnåelse af aktivering af mindst en hydroxylgruppe af FIA, hvor nævnte FIA er i form af et salt, der er opløseligt i det polære aprotiske organiske opløsningsmiddel; (b) at bringe det aktiverede FIA-salt opnået fra trin (a) i kontakt med ethylendiamin (NFI2-CFI2-CFI2-NFI2, indikeret som EDA) til opnåelse af FIA-EDA ved hjælp af nukleofil substitution; (c) at bringe HA-EDA opnået fra trin (b) i kontakt med methacrylsyreanhydrid (indikeret som MA) til opnåelse af HA-EDA-MA ved hjælp af nukleofil substitution.
11. Fremgangsmåde ifølge krav 10, hvor trinnene til fremstilling af HA-EDA-MA-derivaterne alle udføres efter hinanden i den samme beholder.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITFI20140106 | 2014-05-07 | ||
| PCT/EP2015/059941 WO2015169849A1 (en) | 2014-05-07 | 2015-05-06 | Hydrogels of methacrylic hyaluronic acid derivatives for oral enzyme therapy in celiac disease |
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| Publication Number | Publication Date |
|---|---|
| DK3139961T3 true DK3139961T3 (da) | 2018-07-16 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK15725516.7T DK3139961T3 (da) | 2014-05-07 | 2015-05-06 | Hydrogeler af methacryl-hyaluronsyrederivater til oral enzymterapi ved cøliaki |
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| Country | Link |
|---|---|
| US (1) | US10709787B2 (da) |
| EP (1) | EP3139961B1 (da) |
| JP (1) | JP6532483B2 (da) |
| CN (1) | CN106488772B (da) |
| CA (1) | CA2946811C (da) |
| DK (1) | DK3139961T3 (da) |
| ES (1) | ES2675574T3 (da) |
| PT (1) | PT3139961T (da) |
| RU (1) | RU2679638C2 (da) |
| TR (1) | TR201809421T4 (da) |
| WO (1) | WO2015169849A1 (da) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7320788B2 (en) * | 2002-02-14 | 2008-01-22 | The Board Of Trustees Of The Leland Stanford Junior University | Enzyme treatment of foodstuffs for Celiac Sprue |
| JP5060131B2 (ja) * | 2004-09-07 | 2012-10-31 | 中外製薬株式会社 | 水溶性ヒアルロン酸修飾物の製造方法 |
| WO2007044906A2 (en) * | 2005-10-11 | 2007-04-19 | Alvine Pharmaceuticals, Inc. | Compositions and methods for enhanced gastrointestinal stability of oligopeptides and polypeptides |
| ITRM20080636A1 (it) * | 2008-11-28 | 2010-05-29 | Univ Palermo | Procedimento per la produzione di derivati funzionalizzati dell acido ialuronico e relativi idrogeli. |
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2015
- 2015-05-06 WO PCT/EP2015/059941 patent/WO2015169849A1/en active Application Filing
- 2015-05-06 RU RU2016147586A patent/RU2679638C2/ru active
- 2015-05-06 DK DK15725516.7T patent/DK3139961T3/da active
- 2015-05-06 JP JP2016565378A patent/JP6532483B2/ja not_active Expired - Fee Related
- 2015-05-06 CN CN201580022385.4A patent/CN106488772B/zh active Active
- 2015-05-06 EP EP15725516.7A patent/EP3139961B1/en active Active
- 2015-05-06 CA CA2946811A patent/CA2946811C/en active Active
- 2015-05-06 PT PT157255167T patent/PT3139961T/pt unknown
- 2015-05-06 US US15/307,790 patent/US10709787B2/en active Active
- 2015-05-06 TR TR2018/09421T patent/TR201809421T4/tr unknown
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Also Published As
| Publication number | Publication date |
|---|---|
| RU2016147586A (ru) | 2018-06-08 |
| JP2017514836A (ja) | 2017-06-08 |
| ES2675574T3 (es) | 2018-07-11 |
| CN106488772A (zh) | 2017-03-08 |
| TR201809421T4 (tr) | 2018-07-23 |
| CA2946811A1 (en) | 2015-11-12 |
| EP3139961B1 (en) | 2018-04-04 |
| PT3139961T (pt) | 2018-07-13 |
| EP3139961A1 (en) | 2017-03-15 |
| US10709787B2 (en) | 2020-07-14 |
| CA2946811C (en) | 2022-05-03 |
| WO2015169849A1 (en) | 2015-11-12 |
| US20170049896A1 (en) | 2017-02-23 |
| RU2679638C2 (ru) | 2019-02-12 |
| CN106488772B (zh) | 2020-11-27 |
| JP6532483B2 (ja) | 2019-06-19 |
| RU2016147586A3 (da) | 2018-10-05 |
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