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WO2018169314A1 - Timbre d'hydrogel - Google Patents

Timbre d'hydrogel Download PDF

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Publication number
WO2018169314A1
WO2018169314A1 PCT/KR2018/003011 KR2018003011W WO2018169314A1 WO 2018169314 A1 WO2018169314 A1 WO 2018169314A1 KR 2018003011 W KR2018003011 W KR 2018003011W WO 2018169314 A1 WO2018169314 A1 WO 2018169314A1
Authority
WO
WIPO (PCT)
Prior art keywords
growth factor
hydrogel patch
spinal cord
hydrogel
laminin
Prior art date
Application number
PCT/KR2018/003011
Other languages
English (en)
Korean (ko)
Inventor
김정범
Original Assignee
울산과학기술원
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by 울산과학기술원 filed Critical 울산과학기술원
Priority to EP18766653.2A priority Critical patent/EP3449913B1/fr
Priority to US16/305,039 priority patent/US20190167850A1/en
Priority to AU2018236629A priority patent/AU2018236629B2/en
Priority to CN201880002192.6A priority patent/CN109526207B/zh
Priority to JP2018562205A priority patent/JP6750042B2/ja
Priority to CA3029189A priority patent/CA3029189C/fr
Priority claimed from KR1020180029857A external-priority patent/KR102056391B1/ko
Publication of WO2018169314A1 publication Critical patent/WO2018169314A1/fr
Priority to US18/780,922 priority patent/US20240374694A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
    • A61K31/728—Hyaluronic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/36—Blood coagulation or fibrinolysis factors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/39—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
    • 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
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • 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
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • 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
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances

Definitions

  • spinal spinal cord Damage to the central nervous system (spinal spinal cord) involves psychological as well as medical disorders of motor and urinary disorders.
  • spinal cord injury treatment surgical treatment, steroid-based drug treatment such as methylprednisolone, or rehabilitation are being performed.
  • steroid-based drug treatment such as methylprednisolone
  • rehabilitation is being performed.
  • this is only a treatment to alleviate the impairment caused by nerve damage, and there is no fundamental spinal nerve regeneration treatment for impaired spinal nerve regeneration.
  • the hydrogel patch or composition can be one that has an intermediate property between a solid and a liquid.
  • the hydrogel patch or composition may be amorphous, spherical, hemispherical, discotic, or cylindrical.
  • the diameter of the hydrogel patch may be 0.05 mm to 10 cm, 0.1 mm to 5 cm, 0.1 mm to 3 cm, or 0.2 mm to 1.5 cm, and may be provided in such size or shape.
  • the hydrogel patch may be modified in conformity with the shape of the injury site by applying, implanting, attaching, or contacting the target site (for example, tissue damage site).
  • the hydrogel patch or composition can be porous.
  • the surface of the hydrogel patch may have porosity (micropores).
  • the hydrogel patch according to one embodiment has a porosity, thereby enhancing interaction between the active materials.
  • the fibrin or fibrinogen is at a concentration of 0.5 to 20 mg / ml, 0.8 to 16 mg / ml, 0.8 to 12 mg / ml, 1.0 to 10 mg / ml, 2 to 8 mg / ml, or 4 to 8 mg / ml. May be included.
  • the neuronal growth factor may be a brain-derived neurotropic factor (BDNF), a cellular cell derived neurotropic factor (GDNF), a ciliary neurotropic factor (CNTF), a basic fibroblast growth factor (bFGF), a cyclic adenocyne monophosphate (cAMP), or a neurotropin (NT).
  • BDNF brain-derived neurotropic factor
  • GDNF cellular cell derived neurotropic factor
  • CNTF ciliary neurotropic factor
  • bFGF basic fibroblast growth factor
  • cAMP cyclic adenocyne monophosphate
  • NT neurotropin
  • Another aspect is fibrinogen; Laminin or laminin derived peptides; And thrombin added to a composition in a sol (Sol) state comprising hyaluronic acid or a pharmaceutically acceptable salt thereof.
  • the method may further comprise formulating a cell growth factor in the sol state composition.
  • FIG. 1 is a view showing a hydrogel patch manufacturing method and a hydrogel patch of various sizes of 0.3 mm to 0.8 mm according to an embodiment.
  • Hyaluronic acid (Sigma, 53747) 0.1 mg / ml, 0.5 mg / ml or 1 mg / ml;
  • recombinant Human BDNF (Peprotech, 450-02) 10 ng / ml, recombinant Human GDNF (Peprotech, 450-10) 10 ng / ml, recombinant Human NT-3 (Peprotech, 450-03), 5 ng / ml, db- cAMP (Sigma, D0260) 1 uM, T3 (Sigma, T6397) 60 ng / ml, recombinant Human sonic hedgehog (SHH; Peprotech, 100-45) 50 ng / ml, recombinant Human PDGF-AA (Peprotech, 100-13A- 100), recombinant Human FGF-basic (Peprotech, 100-18B) 10 ng / ml and recombinant Human VEGF165 (Peprotech, 100-20) 20 ng / ml.
  • neuronal cells Tuj1 and astrocytes (GFAP) were observed using an inverted fluorescence microscope (Leica, DMI 3000B) attached with a digital monochrome camera (Leica, DFC345 FX). Images observed with inverted fluorescence microscopy were counted by counting the number of neurons or astrocytes using ImageJ (National Institutes of Health (http://rsb.info.nih.gov/ij) software).

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Dermatology (AREA)
  • Zoology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Dispersion Chemistry (AREA)
  • Hematology (AREA)
  • Medicinal Preparation (AREA)
  • Materials For Medical Uses (AREA)

Abstract

La présente invention concerne un timbre d'hydrogel, un procédé de préparation s'y rapportant et une composition comprenant ledit timbre pour le traitement d'une lésion de la moelle épinière. Selon un mode de réalisation, le timbre d'hydrogel a pour effet de permettre de traiter un patient atteint d'une lésion de la moelle épinière d'une manière non invasive pour la moelle épinière.
PCT/KR2018/003011 2017-03-14 2018-03-14 Timbre d'hydrogel WO2018169314A1 (fr)

Priority Applications (7)

Application Number Priority Date Filing Date Title
EP18766653.2A EP3449913B1 (fr) 2017-03-14 2018-03-14 Timbre d'hydrogel
US16/305,039 US20190167850A1 (en) 2017-03-14 2018-03-14 Hydrogel patch
AU2018236629A AU2018236629B2 (en) 2017-03-14 2018-03-14 Hydrogel patch
CN201880002192.6A CN109526207B (zh) 2017-03-14 2018-03-14 水凝胶贴片
JP2018562205A JP6750042B2 (ja) 2017-03-14 2018-03-14 ヒドロゲルパッチ
CA3029189A CA3029189C (fr) 2017-03-14 2018-03-14 Timbre d'hydrogel
US18/780,922 US20240374694A1 (en) 2017-03-14 2024-07-23 Method for manufacturing a pharmaceutical composition for the treatment of spinal cord injury

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR20170032019 2017-03-14
KR10-2017-0032019 2017-03-14
KR1020180029857A KR102056391B1 (ko) 2017-03-14 2018-03-14 하이드로젤 패치
KR10-2018-0029857 2018-03-14

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US16/305,039 A-371-Of-International US20190167850A1 (en) 2017-03-14 2018-03-14 Hydrogel patch
US18/780,922 Continuation-In-Part US20240374694A1 (en) 2017-03-14 2024-07-23 Method for manufacturing a pharmaceutical composition for the treatment of spinal cord injury

Publications (1)

Publication Number Publication Date
WO2018169314A1 true WO2018169314A1 (fr) 2018-09-20

Family

ID=63523615

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2018/003011 WO2018169314A1 (fr) 2017-03-14 2018-03-14 Timbre d'hydrogel

Country Status (1)

Country Link
WO (1) WO2018169314A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN119345113A (zh) * 2024-10-22 2025-01-24 复旦大学 一种负载神经干细胞外泌体的富含脑脊液的丝蛋白水凝胶支架系统、制备方法及其应用

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070010831A1 (en) * 2002-08-01 2007-01-11 Romero-Ortega Mario I Biomimetic biosynthetic nerve implant
KR20110002741A (ko) * 2009-07-02 2011-01-10 아주대학교산학협력단 체내 주입형 하이드로젤 및 이의 생의학적 용도

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070010831A1 (en) * 2002-08-01 2007-01-11 Romero-Ortega Mario I Biomimetic biosynthetic nerve implant
KR20110002741A (ko) * 2009-07-02 2011-01-10 아주대학교산학협력단 체내 주입형 하이드로젤 및 이의 생의학적 용도

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
"Remington's Pharmaceutical Sciences", 1995
ARULMOLI, J. ET AL.: "Combination Scaffolds of Salmon Fibrin, Hyaluronic Acid, and Laminin for Human Neural Stem Cell and Vascular Tissue Engineering", ACTA BIOMATERIALIA, vol. 43, 2016, pages 122 - 138, XP055548151 *
KIM JB ET AL., NAT PROTOC, 2009
LEE, F. ET AL.: "Formation and Stability of Interpenetrating Polymer Network Hydrogels Consisting of Fibrin and Hyaluronic Acid for Tissue Engineering", ACTA BIOMATERIALIA, vol. 9, 2013, pages 5143 - 5152, XP055450790 *
PARK, J. ET AL.: "Nerve Regeneration Following Spinal Cord Injury Using Matrix Metalloproteinase-sensitive, Hyaluronic Acid-based Biomimetic Hydrogel Scaffold Containing Brain-derived Neurotrophic Factor", JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, vol. 93, 2010, pages 1091 - 1099, XP055560185 *
See also references of EP3449913A4 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN119345113A (zh) * 2024-10-22 2025-01-24 复旦大学 一种负载神经干细胞外泌体的富含脑脊液的丝蛋白水凝胶支架系统、制备方法及其应用

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