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WO2020240034A1 - Hydrogel hybride à base d'acide hyaluronique - Google Patents

Hydrogel hybride à base d'acide hyaluronique Download PDF

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Publication number
WO2020240034A1
WO2020240034A1 PCT/EP2020/065102 EP2020065102W WO2020240034A1 WO 2020240034 A1 WO2020240034 A1 WO 2020240034A1 EP 2020065102 W EP2020065102 W EP 2020065102W WO 2020240034 A1 WO2020240034 A1 WO 2020240034A1
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WO
WIPO (PCT)
Prior art keywords
hydrogel
peg
polymer
hyaluronic acid
concentration
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP2020/065102
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English (en)
Inventor
Wenxin Wang
Sigen A
Qian Xu
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University College Dublin
Original Assignee
University College Dublin
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Filing date
Publication date
Application filed by University College Dublin filed Critical University College Dublin
Priority to EP20734111.6A priority Critical patent/EP3976123A1/fr
Publication of WO2020240034A1 publication Critical patent/WO2020240034A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/52—Hydrogels or hydrocolloids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/26—Mixtures of macromolecular compounds

Definitions

  • Hyaluronic acid is a non-sulphated glycosaminoglycan (GAG) and an essential component of the extracellular matrix (ECM) of most tissues. It is composed of alternating units of D-glucuronic acid and N-acetyl-D-glucosamine, linked together via alternating b-1 ,4 and b-1 ,3 glycosidic bonds. It is synthesized at the inner wall of the plasma membrane by HA synthase and is extruded to the ECM space without any further modifications. In the ECM of most tissues, the high molecular weight HA (up to several million Daltons), along with other structural macromolecules, contributes to the mechanical integrity of the network. HA regulates many cellular processes through its binding with cell surface receptors. HA can be rapidly degraded in the body by hyaluronidase and reactive oxygen species, with tissue half- lives ranging from minutes in the blood to hours or days in skin and joints.
  • Previously reported hyaluronic acid hydrogels of the prior art can be regulated only by changing the substitution degree and concentration of HA, resulting in a limited adjustable property. Mixing with another crosslinking polymer can broaden the controlled behaviour of the mechanical property.
  • HA-MA-HDZ has the following structure.
  • the HA-MA has a tailored substitution degree (SD).
  • the degree of substitution (SD) of the HA-MA is at least about 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80% or about 90%.
  • the degree of substitution (SD) of the hydrazide-modified HA-MA is from about 10%, 15%, 20%, 25% to about 90%.
  • the degree of substitution (SD) of the hydrazide-modified HA-MA is from about 30% to about 90%.
  • the degree of substitution (SD) of the hydrazide-modified HA-MA is from about 40% to about 90%.
  • HB-PEG comprises from about 12 to about 30 acrylate groups in the terminal chain of the polymer structure. In an embodiment, there are from about 8 to about 100 acrylate groups in the terminal chain of the polymer structure. In an embodiment, there are from about 20 to 30 acrylate groups in the terminal chain of the polymer structure.
  • the hydrogel is UV-crosslinked.
  • treatment refers to an intervention (e.g. the administration of an agent to a subject) which prevents or delays the onset or progression of a disease or reduces (or eradicates) its incidence within a treated population.
  • treatment is used synonymously with the term“prophylaxis”.
  • an“effective amount” or a“therapeutically effective amount” of an agent defines an amount that can be administered to a subject without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio, but one that is sufficient to provide the desired effect, e.g.
  • hyaluronan or “hyaluronic acid” or “HA” refers to the anionic non-sulphated glycosaminoglycan that forms part of the extracellular matrix in humans and consists of a repeating disaccharide 4) ⁇ -d-GlcpA-(1 3) ⁇ -d-GlcpNAc-(1 .
  • Hyaluronan is the conjugate base of hyaluronic acid, however the two terms are used interchangeably.
  • a salt of hyaluronic acid is employed, the sale is generally a sodium salt, although the salt may be employed such a calcium or potassium salts.
  • the hyaluronic acid or hyaluronan may be obtained from any source, including bacterial sources.
  • glycidyl methacrylate hyaluronic acid refers to a hyaluronic that has been functionalised with glycidyl methacrylate or a derivative thereof.
  • HAGM glycidyl methacrylate hyaluronic acid
  • the stem cell may be selected from the group comprising a side population, embryonic, germinal, endothelial, hematopoietic, myoblast, placental, cord-blood, adipocyte and mesenchymal stem cells.
  • the cells may be engineered to express a biological product, for example a therapeutic biological product such as a growth factor.
  • the current invention provides a hydrogel comprising crosslinked methacryloyl functionalised hyaluronic acid (HA-MA) and hyper-branched poly(ethylene)glycol based, e.g. multi acrylate, (HB-PEG) polymer.
  • Crosslinking can be achieved by any suitable means known in the art, for example including but not limited to, thermal treatment, UV-curing or using a crosslinking agent.
  • crosslinking is UV-curing.
  • the crosslinking may occur in the presence of thiol-crosslinker.
  • the polymers can be crosslinked rapidly to form a biocompatible hydrogel.
  • hydrogel of the invention formed from these two polymers by crosslinking can be tuned (tailored) or modified by altering the amount, and properties of the component polymers. These properties include storage modules, pore size, mechanical properties, swelling and degradation, compress modules, Young’s modules etc. This has not been achieved with hydrogels of the prior art. Naturally, it will be appreciated that the preferred or desired physical properties of the hydrogel of the invention will depend on the intended use of the hydrogel.
  • the hydrogel has a HB-PEG concentration of from about 5% to about 40% (w/v), typically, from about 10% to about 30%, from about 15% to about 25%, typically, about 8%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, 30%, 32%, 34%, 36% or 38% (w/v), or any combination or range thereof.
  • the polymer is UV-crosslinked. In one embodiment, the crosslinking step comprises exposing the polymer to UV light for less than 5, 4, 3, 2, or 1 minutes.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Transplantation (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Dispersion Chemistry (AREA)
  • Materials For Medical Uses (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne un hydrogel comprenant de l'acide hyaluronique fonctionnalisé avec un méthacryloyle (HA-MA) et un polymère multi-acrylate à base de PEG hyper-ramifié (HB-PEG). L'invention concerne en outre des procédés de préparation de l'hydrogel. L'hydrogel ou un dispositif comprenant l'hydrogel trouvent des applications dans l'ingénierie tissulaire et la médecine régénérative.
PCT/EP2020/065102 2019-05-31 2020-05-30 Hydrogel hybride à base d'acide hyaluronique Ceased WO2020240034A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP20734111.6A EP3976123A1 (fr) 2019-05-31 2020-05-30 Hydrogel hybride à base d'acide hyaluronique

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP19177786.1 2019-05-31
EP19177786 2019-05-31

Publications (1)

Publication Number Publication Date
WO2020240034A1 true WO2020240034A1 (fr) 2020-12-03

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PCT/EP2020/065102 Ceased WO2020240034A1 (fr) 2019-05-31 2020-05-30 Hydrogel hybride à base d'acide hyaluronique

Country Status (2)

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EP (1) EP3976123A1 (fr)
WO (1) WO2020240034A1 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113372465A (zh) * 2021-06-25 2021-09-10 苏州浩微生物医疗科技有限公司 一种改性透明质酸钠、制备方法以及应用其制备的微球
CN114573808A (zh) * 2022-03-17 2022-06-03 浙江大学杭州国际科创中心 一种端双键离子响应型超支化聚合物及其制备方法和应用
CN114652889A (zh) * 2022-03-23 2022-06-24 陕西科技大学 一种超支化聚缩水甘油醚水凝胶敷料及其制备方法与应用
CN116217837A (zh) * 2022-09-30 2023-06-06 南京大学 一种超强、超韧、快速回复和抗疲劳水凝胶材料及其制备方法和应用
WO2023178249A1 (fr) * 2022-03-16 2023-09-21 The Regents Of The University Of California Compositions antibactériennes à élution de médicament et procédés
CN116983465A (zh) * 2023-08-07 2023-11-03 北京大学 多巴胺透明质酸粘性水凝胶及其制备方法
CN119488460A (zh) * 2024-11-26 2025-02-21 广州美谛医药生物科技有限公司 一种温敏缓释高效透皮传输凝胶面膜及其制备方法与应用

Citations (11)

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EP1095064A1 (fr) 1998-07-06 2001-05-02 Fidia Advanced Biopolymers S.R.L. Amides d'acide hyaluronique, derives de ce dernier et leurs procede de preparation
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* Cited by examiner, † Cited by third party
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EP0138572A2 (fr) 1983-10-11 1985-04-24 FIDIA S.p.A. Fractions d'acide hyaluronique ayant une activité pharmaceutique, méthodes pour leur préparation et compositions pharmaceutiques les contenant
EP0216453A2 (fr) 1985-07-08 1987-04-01 FIDIA S.p.A. Esters de l'acide hyaluronique et leurs sels.
EP0341745A1 (fr) 1988-05-13 1989-11-15 FIDIA S.p.A. Polysaccharides carboxylés réticulés
US6013679A (en) 1989-08-01 2000-01-11 Anika Research, Inc. Water-insoluble derivatives of hyaluronic acid and their methods of preparation and use
US6013679C1 (en) 1989-08-01 2001-06-19 Anika Res Inc Water-insoluble derivatives of hyaluronic acid and their methods of preparation and use
EP0702699A1 (fr) 1994-03-23 1996-03-27 Fidia Advanced Biopolymers S.R.L. Nouveaux polysaccharides sulfates du type heparine
EP1095064A1 (fr) 1998-07-06 2001-05-02 Fidia Advanced Biopolymers S.R.L. Amides d'acide hyaluronique, derives de ce dernier et leurs procede de preparation
EP1313772A1 (fr) 2000-08-31 2003-05-28 FIDIA FARMACEUTICI S.p.A. Nouveaux derives reticules d'acide hyaluronique
EP1339753A2 (fr) 2000-08-31 2003-09-03 FIDIA FARMACEUTICI S.p.A. Polysaccharides percaboxyles, et procede d'elaboration
US8124120B2 (en) 2003-12-22 2012-02-28 Anika Therapeutics, Inc. Crosslinked hyaluronic acid compositions for tissue augmentation
US20090281056A1 (en) 2005-12-01 2009-11-12 Shiseido Co., Ltd. Cationized Hyaluronic Acid
US20100197904A1 (en) 2007-04-24 2010-08-05 Q. P. Corporation Cationized hyaluronic acid and/or salt thereof, method of producing the same, hair modifying agent, cuticle repairing agent, skin modifying agent, and cosmetic preparation each using the same

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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113372465A (zh) * 2021-06-25 2021-09-10 苏州浩微生物医疗科技有限公司 一种改性透明质酸钠、制备方法以及应用其制备的微球
WO2023178249A1 (fr) * 2022-03-16 2023-09-21 The Regents Of The University Of California Compositions antibactériennes à élution de médicament et procédés
CN114573808A (zh) * 2022-03-17 2022-06-03 浙江大学杭州国际科创中心 一种端双键离子响应型超支化聚合物及其制备方法和应用
CN114573808B (zh) * 2022-03-17 2023-07-25 浙江大学杭州国际科创中心 一种端双键离子响应型超支化聚合物及其制备方法和应用
CN114652889A (zh) * 2022-03-23 2022-06-24 陕西科技大学 一种超支化聚缩水甘油醚水凝胶敷料及其制备方法与应用
CN116217837A (zh) * 2022-09-30 2023-06-06 南京大学 一种超强、超韧、快速回复和抗疲劳水凝胶材料及其制备方法和应用
CN116983465A (zh) * 2023-08-07 2023-11-03 北京大学 多巴胺透明质酸粘性水凝胶及其制备方法
CN119488460A (zh) * 2024-11-26 2025-02-21 广州美谛医药生物科技有限公司 一种温敏缓释高效透皮传输凝胶面膜及其制备方法与应用
CN119488460B (zh) * 2024-11-26 2025-10-31 广州美谛医药生物科技有限公司 一种温敏缓释高效透皮传输凝胶面膜及其制备方法与应用

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