WO2018093161A1 - Nouvel agent hémostatique comprenant une protéine adhésive de moule et son procédé de préparation - Google Patents

Nouvel agent hémostatique comprenant une protéine adhésive de moule et son procédé de préparation Download PDF

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WO2018093161A1
WO2018093161A1 PCT/KR2017/012991 KR2017012991W WO2018093161A1 WO 2018093161 A1 WO2018093161 A1 WO 2018093161A1 KR 2017012991 W KR2017012991 W KR 2017012991W WO 2018093161 A1 WO2018093161 A1 WO 2018093161A1
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WIPO (PCT)
Prior art keywords
component
mussel adhesive
hemostatic
protein
hemostatic composition
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PCT/KR2017/012991
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English (en)
Korean (ko)
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차형준
김효정
이재윤
전은영
박태윤
최근호
최봉혁
주계일
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포항공과대학교 산학협력단
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Publication of WO2018093161A1 publication Critical patent/WO2018093161A1/fr

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    • 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
    • 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
    • A61K38/1767—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
    • 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
    • A61K47/00—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
    • A61K47/50—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
    • A61K47/51—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
    • A61K47/62—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 a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—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
    • A61K47/50—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
    • A61K47/51—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
    • A61K47/62—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 a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/6435—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent the peptide or protein in the drug conjugate being a connective tissue peptide, e.g. collagen, fibronectin or gelatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—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
    • A61K47/50—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
    • A61K47/69—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—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
    • A61K47/50—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
    • A61K47/69—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6903—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being semi-solid, e.g. an ointment, a gel, a hydrogel or a solidifying gel
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—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
    • A61K47/50—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
    • A61K47/69—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6953—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a fibre, a textile, a slab or a sheet

Definitions

  • Rapid and safe emergency hemostasis plays an important role in preventing excessive bleeding and subsequent life threats in case of injury in everyday life and on the job site.
  • effective hemostasis in the affected area can reduce the amount of bleeding in the patient, reduce the amount of blood transfusion, and reduce the time and cost of the surgery by securing the vision of the surgeon.
  • physical compression such as bandages, gauze, surgical sutures, staplers, or other methods such as electric, ultrasound, or lasers may be used, but it may cause bleeding, damage, and infection.
  • Hemostatic drugs have a comparative advantage in terms of safety and efficiency because they can prevent bleeding and prevent damage and infection of wound tissues by using physical, chemical and physiological activities, depending on the product when introduced into the bleeding site.
  • Figure 3 is a graph showing the Young's modulus of the hydrogel material and mussel adhesive protein / anemone silk protein photocrosslinked hydrogel material comprising the mussel adhesive protein prepared according to Example 1.
  • the line segment in the middle of the bar graph represents the standard deviation.
  • Figure 4 is a graph showing the results of measuring the degree of blood coagulation using the 540nm wavelength absorbance when using the hydrogel prepared according to Example 1.
  • the line segment in the middle of the bar graph represents the standard deviation.
  • Example 6 is a photograph confirming that the bleeding is reduced in the mouse when using the hydrogel prepared according to Example 1.
  • Example 7 is an electron micrograph showing that the colloidal solution prepared according to Example 2 activates platelet activity.
  • the mussel adhesive protein is fp-151 (SEQ ID NO: 7), fp-131 (SEQ ID NO: 8), fp-353 (SEQ ID NO: 9), fp-153 (SEQ ID NO: 10), and fp-351 (SEQ ID NO: 10) No. 11) may be one or more selected from the group consisting of.
  • Mussel adhesive protein is known to have a hemostatic effect as well as activating platelets, as well as adhesion effects.
  • the colloidal solution may include coacervate formed from the first component and the second component.
  • the second component may be an anionic polymer.
  • the anionic polymer may be further added to the first component and the second component.
  • the spray may be a spray application of a mixture of the first and second components to the trauma and surgical site.
  • the blood reacted according to Experimental Example 1 was centrifuged at 12,000 rpm for 30 minutes to separate plasma, diluted 200-fold with distilled water, and the concentration of PF4 present in the sample was analyzed by ELISA.
  • Each sample was added to 100 ⁇ m in 96-well microplates coated with PF4 capture antibody and blocked with BSA, and reacted at room temperature for 2 hours.
  • Each well was washed three times with 300 ⁇ m wash buffer. Thereafter, 100 ⁇ m of the detection antibody solution was added thereto, and the reaction was performed at room temperature for 2 hours. Then 100 ⁇ m streptavidin-HRP solution was added to the reaction in the dark for 20 minutes, each well was washed.

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

Abstract

La présente invention concerne une composition hémostatique, un agent hémostatique comprenant celle-ci, et son procédé de préparation. La composition hémostatique comprend : une protéine adhésive de moule en tant que premier composant; et un polymère d'origine biologique autre que la protéine adhésive de moule en tant que deuxième composant. La présente invention présente d'excellents biocompatibilité, biodégradabilité, effets hémostatiques dans des environnements sous-marins, et des propriétés mécaniques adaptées pour des environnements tissulaires.
PCT/KR2017/012991 2016-11-16 2017-11-16 Nouvel agent hémostatique comprenant une protéine adhésive de moule et son procédé de préparation WO2018093161A1 (fr)

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KR20160152646 2016-11-16
KR10-2016-0152646 2016-11-16

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111892720A (zh) * 2020-07-29 2020-11-06 苏州大学 碱性磷酸酶诱导蚕丝蛋白溶液凝胶化和仿生矿化的方法
CN111991608A (zh) * 2020-08-27 2020-11-27 振德医疗用品股份有限公司 一种创面覆盖物及其制备方法
CN116196466A (zh) * 2023-03-16 2023-06-02 西安德诺海思医疗科技有限公司 贻贝粘蛋白乳膏剂敷料及其制备方法
CN116515164A (zh) * 2023-05-26 2023-08-01 南京工业大学 一种贻贝蛋白抗菌水凝胶及其制备方法与应用

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KR102211765B1 (ko) 2019-01-15 2021-02-03 주식회사 테라시온바이오메디칼 흡수성 골 지혈재 조성물 및 이를 이용한 골 지혈재 제조방법
KR20220077353A (ko) 2020-12-02 2022-06-09 주식회사 테라시온 바이오메디칼 항생제를 포함하는 흡수성 골 지혈재 조성물 및 이의 제조방법

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111892720A (zh) * 2020-07-29 2020-11-06 苏州大学 碱性磷酸酶诱导蚕丝蛋白溶液凝胶化和仿生矿化的方法
CN111892720B (zh) * 2020-07-29 2021-07-13 苏州大学 碱性磷酸酶诱导蚕丝蛋白溶液凝胶化和仿生矿化的方法
CN111991608A (zh) * 2020-08-27 2020-11-27 振德医疗用品股份有限公司 一种创面覆盖物及其制备方法
CN111991608B (zh) * 2020-08-27 2021-10-01 振德医疗用品股份有限公司 一种创面覆盖物及其制备方法
CN116196466A (zh) * 2023-03-16 2023-06-02 西安德诺海思医疗科技有限公司 贻贝粘蛋白乳膏剂敷料及其制备方法
CN116515164A (zh) * 2023-05-26 2023-08-01 南京工业大学 一种贻贝蛋白抗菌水凝胶及其制备方法与应用
CN116515164B (zh) * 2023-05-26 2024-03-19 南京工业大学 一种贻贝蛋白抗菌水凝胶及其制备方法与应用

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