WO2015088275A1 - Composition d'étanchéité ou adhésive médicale biodégradable - Google Patents

Composition d'étanchéité ou adhésive médicale biodégradable Download PDF

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Publication number
WO2015088275A1
WO2015088275A1 PCT/KR2014/012265 KR2014012265W WO2015088275A1 WO 2015088275 A1 WO2015088275 A1 WO 2015088275A1 KR 2014012265 W KR2014012265 W KR 2014012265W WO 2015088275 A1 WO2015088275 A1 WO 2015088275A1
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Prior art keywords
oxidized
component
composition
adhesion
hyaluronic acid
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PCT/KR2014/012265
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English (en)
Korean (ko)
Inventor
이은혜
맹진희
김근수
이돈행
박영환
Original Assignee
재단법인 유타 인하 디디에스 및 신의료기술개발 공동연구소
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Priority claimed from KR1020140089173A external-priority patent/KR101664444B1/ko
Application filed by 재단법인 유타 인하 디디에스 및 신의료기술개발 공동연구소 filed Critical 재단법인 유타 인하 디디에스 및 신의료기술개발 공동연구소
Priority to JP2016538741A priority Critical patent/JP6207745B2/ja
Priority to CN201480067775.9A priority patent/CN106061518B/zh
Priority to EP14870365.5A priority patent/EP3081236B1/fr
Priority to US15/102,406 priority patent/US10105465B2/en
Priority to CA2933271A priority patent/CA2933271C/fr
Priority to AU2014360958A priority patent/AU2014360958B2/en
Priority to RU2016128376A priority patent/RU2657836C1/ru
Priority to MX2016007688A priority patent/MX366143B/es
Publication of WO2015088275A1 publication Critical patent/WO2015088275A1/fr

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    • 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
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/08—Polysaccharides
    • 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
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A61L24/0031—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
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A61L24/0042—Materials resorbable by the body
    • 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
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
    • A61L26/0023—Polysaccharides
    • 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
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061—Use of materials characterised by their function or physical properties
    • A61L26/008—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
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061—Use of materials characterised by their function or physical properties
    • A61L26/009—Materials resorbable by the body
    • 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
    • A61L27/20—Polysaccharides
    • 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
    • A61L27/58—Materials at least partially resorbable by the body
    • 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/04—Macromolecular materials
    • A61L31/042—Polysaccharides
    • 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/145—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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/148—Materials at least partially resorbable by the body

Definitions

  • the present invention relates to a biodegradable medical adhesive or sealant composition
  • a biodegradable medical adhesive or sealant composition comprising an oxidized glycosaminoglycan having a formyl group and a polyamine.
  • Bioadhesives and sealants are used to seal or apply tissues during surgery, or to be used as anti-bleeding agents (hemostasis), body fluids and blood blockers. Bioadhesives and sealants require biocompatibility as they come into contact with the skin. It must be absent, biodegradable, and not interfere with the healing of living organisms.
  • cyanoacrylates include cyanoacrylates, fibrin glues, gelatin glues, and polyurethanes. Closure Medi Cal of the United States commercialized a medical tissue adhesive of octylcyanoacrylate called Dermabond in 1997. It was approved by the US FDA in 1998 after it was approved by the European Community in August. However, cyanoacrylate-based adhesives may interfere with wound healing because the solids lack rigidity and rigidity, and are difficult to decompose in vivo, and thus are easily encapsulated and become foreign matters. there was. In addition, since fibrin glue has a considerably low adhesive force, the generated fibrin fish may drop from the tissue, and since the blood product is a blood product, there is a problem of a viral infection.
  • Korean Patent Publication No. 10-2009-0083484 discloses a medical two-component adhesive comprising an aldehyde-ized textan powder and an ⁇ -poly—L-lysine powder prepared by mechanical grinding after lyophilization.
  • LYDEX, Rydex is disclosed.
  • the two-component adhesive is characterized in that it is a powdered medical adhesive, it takes a relatively long time to decompose the gel, there is a problem that does not obtain a satisfactory effect in the water absorption.
  • new products with improved characteristics in terms of decomposition time, adhesion and water absorption There is an increasing demand for medical adhesives.
  • numerous citations and patent documents are referenced and their citations are indicated. The disclosures of cited papers and patent documents are incorporated herein by reference in their entirety, and the level of the technical field to which the present invention belongs and the contents of the present invention are more clearly explained.
  • the present inventors can perform sufficient adhesion, coating and hemostasis even in the part of the body where body fluid and blood are present, and can absorb a large amount of water, especially compared to other biodegradable polymers, and can decompose itself in the body. And research efforts were made to develop sealants. As a result, the present invention is confirmed that the use of a formyl group and oxidized glycosaminoglycan and polyamine together can effectively bond, layer, apply, prevent adhesion, wound coating and hemostasis of living tissues. It was completed.
  • an object of the present invention is to provide a medical adhesive or sealant (or a medical adhesive or sealant composition).
  • Another object of the present invention is to provide a method for adhesion, layer deposition, application, adhesion prevention, wound coating or hemostasis of living tissue.
  • the invention provides a biodegradable medical adhesive or sealant (or medical adhesive or sealant composition) comprising:
  • a first component comprising an oxidized glycosaminoglycan in which a formyl group is introduced and oxidized
  • a second component comprising a polyamine having two or more amino groups, wherein the pH in the aqueous solution state of the second component is 8.5 to 11.0.
  • the invention provides a biodegradable medical adhesive or sealant (or medical adhesive or sealant composition) comprising:
  • a second component comprising a polyamine having two or more amino groups, the pH in the aqueous solution state of the second component is 8.5 to 11.0,
  • the present invention is the step of applying the biodegradable medical adhesive or sealant (or medical adhesive or sealant composition) to a biological tissue that requires adhesion, layering, application, adhesion prevention, wound coating or hemostasis It provides a method of adhesion, layer deposition, coating, adhesion prevention, wound coating or hemostasis of a biological tissue comprising a.
  • the present inventors can perform sufficient adhesion, coating and hemostasis even in the part of the body where body fluids and blood are present, and in particular, can absorb a large amount of water compared to other biodegradable polymers and can decompose itself in the body. And research efforts were made to develop sealants.
  • the composition of the present invention showed an improved effect on gel formation time, adhesion and water absorption than the conventional medical two-component adhesive (LYDEX) (see Tables 5 to 7), In addition, it showed a better effect than the conventional hemostatic agent (Ar i sta TM AH) (see Fig. 12).
  • the composition of the present invention comprises oxidized glycosaminoglycan as the first component.
  • oxidized glycosaminoglycan means that a formyl group (-CH0) is introduced and oxidized to glycosaminoglycan.
  • the glycosamino glycan is distinguished from glucan, which is a 0-glycoside bond of a monosaccharide, in that it is a polysaccharide having a repeating structure of a disaccharide including nucleosamine.
  • Introduction of such a formyl group can be performed by a periodic acid oxidation method.
  • oxidized glycosaminoglyco introduced with the appropriate number (eg, 0.01 to 0.95) formyl groups per anhydrous glucose unit (sugar moiety) by oxidation with glycosaminoglycanol periodic acid or periodicate You can get a space.
  • Oxidation degree of this glycosaminoglycan Calculated according to, having a value from 10 to 99.5%. Oxidized glycosaminoglycans having such a degree of oxidation, when used in combination with the second component, can quickly absorb the blood and body fluids in the body and gelate quickly.
  • the oxidation degree of the oxidized glycosaminoglycan is
  • the oxidation degree of the oxidized hyaluronic acid may be 10-20%.
  • Oxidation degree measurement of the glycosaminoglycan can be carried out by NaOH scoring method. For example, 17.5 g of hydroxylamine hydrochloride and 0.05% methyl orange 6 are mixed in 994 distilled water to form a solution of 0.25 ⁇ / ⁇ hydroxylamine hydrochloride, titrated ⁇ to 4, and then Dissolve 0.1 g of minoglycan in 25 ⁇ of the above solution, titrate it again to pH 4 with 0.1 ⁇ / i sodium hydroxide, , , ⁇ , , ,
  • the oxidized glycosaminoglycan has 0.01 to 0.95 formyl groups per anhydrous glucose unit (sugar residues).
  • the oxidized glycosaminoglycan is composed of oxidized hyaluronic acid, oxidized chondroitin sulfate, oxidized chondroitin, dermatan sulphate, oxidized heparan sulphate, heparin oxidized and keratan oxidized. Is selected from.
  • the gelling ability of the adhesive / sealant composition by using a glycosaminoglycan having a specific molecular weight, the gelling ability of the adhesive / sealant composition, the gelation state retention time, the elasticity of the gel, and the like can be appropriately controlled.
  • the glycosaminoglycan used to obtain the oxidized glycosaminoglycan has a molecular weight of 1,000 to 5 million.
  • the glycosaminoglycan used to obtain the oxidized glycosaminoglycan is 10,000 to 4 million, 50,000 to 350, 100,000 to 350, 100,000 to 3 million, 100,000 to 2.5 million, 100,000 To 2 million, or 100,000 to 1.6 million molecular weight.
  • the first component is 100,000 to
  • Oxidized hyaluronic acid with a molecular weight of 2 million is included. According to one specific example, the molecular weight of the oxidized hyaluronic acid is 100,000 to 1.6 million.
  • the first component includes two or more kinds of oxidized glycosaminoglycans.
  • the weight ratio of these oxidized glycosaminoglycans is 1: 0.5-5. According to one specific example, the weight ratio of the oxidized glycosaminoglycan is 1: 0.5-4, and in another specific example 1: 0.5.
  • the two or more kinds of oxidation Glycosaminoglycans are oxidized hyaluronic acid and oxidized chondroitin sulfate.
  • the weight ratio of the hyaluronic acid oxide and chondroitin oxide is 1: 0.5-5, 1: 0.5-4, 1: 0.5-3.5, 1: 0.5-3, 1: 0.5-2.5, 1: 0.5-2, 1: 0.5 -1.5 or 1: 0.8-
  • the oxidation degree of the oxidized hyaluronic acid is 10-.
  • the oxidation degree of the oxidized hyaluronic acid is 12-40%, in another specific example 12-383 ⁇ 4>, and in another specific example 13-3.
  • the oxidation degree of the oxidized chondroitin sulfate is 10-55%.
  • the oxidation degree of the chondroitin sulfate is 10-50%, in another specific example 10-45%, in another specific example 10-40%, in another specific example 10 -35%.
  • the first component is in powder, liquid or solid (eg pellet form).
  • the powdery first component may be obtained by drying (eg, spray drying, lyophilization, etc.) of an oxidized glycosaminoglycan-containing solution followed by grinding (eg, mechanical grinding).
  • composition of the present invention further comprises a second component comprising a polyamine having two or more amino groups in addition to the first component as the active component.
  • the second component exhibits a pH of 8.5-11.0 in aqueous solution. As confirmed in the following examples, when the pH in the aqueous solution state of the second component is 8.5-11.0, gelation may be performed within a few seconds (see FIG. 7).
  • the second component is 9.0- in an aqueous solution state.
  • the pleamine may further have a secondary and / or tertiary amino group.
  • the second component comprising the polyamine is in powder, liquid or solid (eg, pellets).
  • the powdery second component can be obtained by drying and grinding the polyamine-comprising solution.
  • the polyamine-containing solution may further include a pH adjusting agent so that the pH range in the aqueous solution state of the second component is 8.5-11.0.
  • the pH regulator include monovalent or polyvalent carboxylic acid compounds such as acetic acid, citric acid, succinic acid, glutaric acid, malic acid, fumaric acid and maleic acid, or anhydrides thereof.
  • the polyamine is polylysine, chitosan, albumin, putrescine (putrescine), cadaverine (cadaver ine), spermidine, spermine (spermine), protamine and PEI (Polyethylenimine) is selected from the group consisting of.
  • the polyamine has a molecular weight of 100 or more.
  • the molecular weight of the polyamine may be 1,000 to 200,000.
  • the polyamine is poly-L-lysine.
  • the poly-L-lysine may be ⁇ -poly-L-lysine produced using microorganisms (eg, Straptomyces abulus) or enzymes.
  • the second component may further comprise a ⁇ regulator in addition to the polyamine.
  • the composition of the present invention may further comprise a drug.
  • the drug may be included in the second component.
  • the drug is
  • It may have one or more amine groups, and examples of such drugs include anthracycline-based drugs, gemcitabine, vancomycin, polymycin, methotrexate, protein drugs and peptide drugs.
  • anthracycline-based drugs gemcitabine, vancomycin, polymycin, methotrexate, protein drugs and peptide drugs.
  • the amine group of the drug may also act as the formyl group of the first component, and the three components may form a gel together.
  • the composition of the present invention may be formulated in various forms, for example, a first component which is in powder form, liquid form or solid form (for example, pellet form), and is in powder form, liquid form or solid form. Combinations of second components.
  • the composition of the present invention comprises the first component and the second component in a weight ratio of 0.5-10: 1.
  • the first component and the second component are included in a weight ratio of 0.5-8: 1, in another specific example, a weight ratio of 0.5-6: 1, and in another specific example, 0.5-4: 1 Weight ratio, in another specific example a weight ratio of 0.5-3: 1, in another specific example, a weight ratio of 0.5-2: 1, in another specific example, a weight ratio of 0.5-1.5: 1, and in another specific example, 0.8-1.5: Weight ratio of 1, and in another specific example, weight ratio of 0.8-1.2: 1.
  • the present invention by controlling the ratio of the formyl group of the first component and the amino group of the second component it is possible to control the gel formation time, the decomposition time of the resulting gel and the like.
  • the molar ratio of formyl group / amino group is 0.1-500.
  • the molar ratio of formyl group / amino group is 1-400, 1_350 in another specific example, 1-300 in another specific example, and another specific example. In the example, 10–300.
  • the first component and the second component may be applied to the adherend (skin surface inside and outside the living body) simultaneously or sequentially for a medical effect (medical use).
  • a medical effect medical use
  • saline or distilled water may be sprayed in order to gel the first and second components.
  • the medical use is selected from the group consisting of adhesion, layer deposition, application, adhesion prevention, wound coating and hemostasis of biological tissue.
  • the composition of the present invention provides the first component and the second component in a form contained in the same container, or in a form separately contained in a separate container.
  • the present invention provides a biodegradable medical adhesive or sealant composition comprising an oxidized glycosaminoglycan and a polyamine.
  • composition of the present invention shows an improved effect in biodegradable coating properties, gelation time, hemostatic capacity, adhesion and water absorption.
  • composition of the present invention can be utilized for various medical applications in which medical adhesives or sealants can be used, such as adhesion, layering, coating, adhesion prevention, wound coating, leakage prevention, and hemostasis of biological tissues.
  • Figure 1 shows the results of the analysis of oxidized hyaluronic acid using an FT-IR spectrometer.
  • FIG. 3 is a photograph showing the results of gelation evaluation of the first and second component mixtures mixed in different weight ratios.
  • Figure 4 is a photograph showing a comparison of the gelation time of the adhesive and sealant composition of the present invention and the conventional adhesive composition (Lydex).
  • 5 is a graph showing the adhesive strength of the adhesive and sealant composition of the present invention and the conventional adhesive composition (Litex).
  • Figure 6 is a photograph showing the results (mucoadhesion and hemostatic capacity) after applying the adhesive and sealant composition of the present invention, or a conventional adhesive composition (Lydex) to the bleeding site after gastric mucosal resection.
  • Figure 7 is a photograph showing the gelation state and gelation time of the oxidized glycosaminoglycans and polyamine mixtures and the gelation according to pH.
  • FIGS. 8 to 11 show the results of comparative experiments between the adhesive and sealant composition of the present invention and the conventional hemostatic agent (Ar i sta TM AH) performed on the mesenchymal resection model, nephrectomy model, gastric mucosal resection model, and blood vessel application model.
  • . 12 is a graph quantitatively showing the results of FIGS. 8 to 11.
  • the oxidized hyaluronic acid obtained here was lyophilized for at least 4 days, then pulverized and passed through a 500 ⁇ sized mesh to obtain an oxidized hyaluronic acid having a diameter of about 500 im or less.
  • Oxidized hyaluronic acid was analyzed using an FT-IR spectrometer (Cary 640, Agilent Technologies, USA), and the substituent was confirmed at 4000-400 cm ' Hresolution 4 cm- 1 (FIG. 1).
  • chitosan, protamine, PEI, polylysine, spermine, spermidine, and albumin were used as second components, and pH adjusters (acid, acid, base, base salt, etc.) from 5% by weight or more of aqueous polyamine solution After adjusting the pH to 8.5, 9.0, 9.5 and 10 using the same as in the case of the oxidized hyaluronic acid / oxidized chondroitin sulfate, the powder obtained after freeze drying was used.
  • Example 1 The first and second components obtained in Example 1 were mixed in different weight ratios (1: 1, 2: 1,
  • LYDEX showed an average adhesive strength of 53.6 gf even though a small amount (500 water was applied) of LYDEX compared to the oxidized hyaluronic acid mixture. Measured at 65.9 and 67.5 gf (FIG. 5 and Table 6).
  • a mucosectomy-induced gastric bleeding model in rabbits was constructed as follows.
  • the rabbits were fasted for 24 hours prior to surgery and anesthetized by intramuscular injection of a combination of ketamine (4.2 mg / kg) and silazine (11.7 mg / kg).
  • the upper abdomen of the rabbit was incised to expose the stomach and incision about 5-7 cm along the great curvature of the stomach.
  • Isotonic saline 200 was injected into the submucosal layer of the stomach, and the swollen gastric mucosa was excised using surgical scissors. The diameter of the excised site was about 7-10 mm 3.
  • the degree of substitution (oxidation degree) of hyaluronic acid and chondroitin sulfate was confirmed by NaOH titration. Specifically, 17.5 g of hydroxylamine hydrochloride and 0.05% methyl orange 6 11 were mixed in 994 ⁇ distilled water to make a 0.25 1 ⁇ 1 / £ hydroxylamine hydrochloride solution and the pH was titrated to 4. 0.1 g of hyaluronic acid black silver chondroitin sulfate was dissolved in 25 m of the above solution and titrated again to pH 4 with 0.1 ⁇ / ⁇ sodium hydroxide. Substitution degree (%) was calculated using the following formula, and the results were as shown in Tables 8 and 9. Equation 3
  • chitosan, protamine PEI, polylysine, spermine, spermidine, and albumin were selected as the second component, and as a second component, to find out whether the gelation was performed according to pH.
  • aqueous solution after adjusting the pH to various ranges (5.5-6.4, 6.5-7.4, 7.5-8.4, 8.5-9.4, 9.5-10.4, 10.5-11), the same as in the case of the oxidized hyaluronic acid / oxidized chondroitin sulfate
  • the powder obtained after freeze drying was used. Oxidized hyaluronic acid / oxidized chondroitin sulfate of the first component and polyamine were mixed.
  • Anesthesia was injected by injection of a ketamine and lump mixture into the abdominal cavity of male SD rats weighing 200-300 g, and the central upper abdomen was incised approximately 3-4 cm in length or width.
  • the mesenchyme was exposed using a wet gauze into the incision of the incised abdomen, and the portal vein and hepatic artery were ligated with a vascular clip. About 1 cm away from the edge of the mesenchyme was excised with surgical scissors and 50-100 mg of UI-SAH was applied.
  • Ar i sta TM AH (Medafor Inc., USA) was applied. After application, the ligated clip was removed after ligating, and the amount of bleeding was measured using sterile gauze.
  • Anesthesia was injected by injection of a ketamine and lump mixture into the abdominal cavity of male SD rats weighing 200-300 g, and the central upper abdomen was incised about 5-6 cm vertically or horizontally.
  • the portal vein was exposed after moving other organs to the left axis through the incised abdominal gap.
  • Two sites above and below the portal vein were ligated with a vascular clip.
  • UI-SAH 50-100 mg was applied after puncturing the portal vein using an 18 gauge needle.
  • Ar i sta TM AH (Medafor Inc., USA) was applied. After application, the ligated clip was removed after removing the ligated clip, and the bleeding amount was measured using sterile gauze.

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Abstract

La présente invention concerne une composition d'étanchéité ou adhésive médicale biodégradable contenant un glycosaminoglycane oxydé et une polyamine. La composition de la présente invention présente une amélioration des effets en termes de biodégradation, de propriété de revêtement, de temps de prise en gel, de capacité hémostatique, de force adhésive, de capacité d'absorption de l'humidité et similaire, et convient donc à diverses applications médicales utilisant un adhésif ou un colmatant, comme l'adhérence d'un tissu biologique, le remplissage, le revêtement, la prévention des adhérences, le revêtement des plaies, la prévention des fuites et l'hémostase.
PCT/KR2014/012265 2013-12-13 2014-12-12 Composition d'étanchéité ou adhésive médicale biodégradable WO2015088275A1 (fr)

Priority Applications (8)

Application Number Priority Date Filing Date Title
JP2016538741A JP6207745B2 (ja) 2013-12-13 2014-12-12 生分解性医療用接着剤又はシーラント組成物
CN201480067775.9A CN106061518B (zh) 2013-12-13 2014-12-12 生物降解性医疗用粘结剂或密封剂组合物
EP14870365.5A EP3081236B1 (fr) 2013-12-13 2014-12-12 Composition d'étanchéité ou adhésive médicale biodégradable
US15/102,406 US10105465B2 (en) 2013-12-13 2014-12-12 Biodegradable medical adhesive or sealant composition
CA2933271A CA2933271C (fr) 2013-12-13 2014-12-12 Composition d'etancheite ou adhesive medicale biodegradable
AU2014360958A AU2014360958B2 (en) 2013-12-13 2014-12-12 Biodegradable medical adhesive or sealant composition
RU2016128376A RU2657836C1 (ru) 2013-12-13 2014-12-12 Биоразлагаемая медицинская клеящая или герметизирующая композиция
MX2016007688A MX366143B (es) 2013-12-13 2014-12-12 Composicion sellante o adhesiva medica biodegradable.

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR20130155722 2013-12-13
KR10-2013-0155722 2013-12-13
KR1020140089173A KR101664444B1 (ko) 2013-12-13 2014-07-15 생분해성 의료용 접착제 또는 실란트 조성물
KR10-2014-0089173 2014-07-15

Publications (1)

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WO2015088275A1 true WO2015088275A1 (fr) 2015-06-18

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Country Status (1)

Country Link
WO (1) WO2015088275A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112451735A (zh) * 2019-09-09 2021-03-09 天津大学 一种基于ε-聚赖氨酸的仿贻贝配位粘合剂及其制备方法
CN116687959A (zh) * 2022-05-18 2023-09-05 朱小丰 一种硫酸软骨素生物多胺复合物、其制备方法及用途

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20050045113A (ko) * 2003-11-10 2005-05-17 주식회사 바이오레인 기포를 포함하는 유착방지제
US20050238702A1 (en) * 2002-04-23 2005-10-27 Netech, Inc Medical composition containing photocrosslinkable chitosan derivative
JP2006347883A (ja) * 2003-09-08 2006-12-28 Neetec:Kk 糖鎖含有キトサン誘導体及びグリコサミノグリカンを含有する医療用組成物
KR20070100230A (ko) * 2007-04-05 2007-10-10 베이코 테크 리미티드 히알루론산으로 코팅된 골 임플란트 장치
KR20090083484A (ko) 2006-11-30 2009-08-03 가부시끼가이샤 비엠지 자기 분해성을 갖는 분체­액체 및 분체­분체의 2 반응제형 의료용 접착제
KR20120089506A (ko) * 2010-12-10 2012-08-13 포항공과대학교 산학협력단 히알루론산-단백질 컨쥬게이트 및 이의 제조 방법

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050238702A1 (en) * 2002-04-23 2005-10-27 Netech, Inc Medical composition containing photocrosslinkable chitosan derivative
JP2006347883A (ja) * 2003-09-08 2006-12-28 Neetec:Kk 糖鎖含有キトサン誘導体及びグリコサミノグリカンを含有する医療用組成物
KR20050045113A (ko) * 2003-11-10 2005-05-17 주식회사 바이오레인 기포를 포함하는 유착방지제
KR20090083484A (ko) 2006-11-30 2009-08-03 가부시끼가이샤 비엠지 자기 분해성을 갖는 분체­액체 및 분체­분체의 2 반응제형 의료용 접착제
KR20070100230A (ko) * 2007-04-05 2007-10-10 베이코 테크 리미티드 히알루론산으로 코팅된 골 임플란트 장치
KR20120089506A (ko) * 2010-12-10 2012-08-13 포항공과대학교 산학협력단 히알루론산-단백질 컨쥬게이트 및 이의 제조 방법

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112451735A (zh) * 2019-09-09 2021-03-09 天津大学 一种基于ε-聚赖氨酸的仿贻贝配位粘合剂及其制备方法
CN116687959A (zh) * 2022-05-18 2023-09-05 朱小丰 一种硫酸软骨素生物多胺复合物、其制备方法及用途

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