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Combination of cross-linked hyaluronic acids and method of preparing the same

a technology of cross-linked hyaluronic acid and cross-linked comb, which is applied in the field of preparation of cross-linked hyaluronic acid and a combination, can solve the problems that hyaluronic acid of animal origin such as rooster combs may have a quality control problem, and achieve the effect of low viscoelasticity and effective use in osteoarthritis treatmen

Inactive Publication Date: 2018-08-02
HANMI PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present disclosure provides a method for preparing a cross-linked hyaluronic acid using an epoxy-based cross-linking agent in an aqueous alkaline solution. The method involves adding ethanol to the solution to reduce the viscoelasticity of the cross-linked hyaluronic acid. By adjusting the reaction conditions, a combination of cross-linked hyaluronic acids with different viscoelasticities can be prepared. This allows for the formation of a biocompatible combination with a viscoelasticity similar to that of human synovial fluid, which is effective in treating osteoarthritis.

Problems solved by technology

However, hyaluronic acids of animal origin such as from rooster combs may have a quality control problem due to animal-origin viruses and inconsistent quality of source material.

Method used

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  • Combination of cross-linked hyaluronic acids and method of preparing the same
  • Combination of cross-linked hyaluronic acids and method of preparing the same
  • Combination of cross-linked hyaluronic acids and method of preparing the same

Examples

Experimental program
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Effect test

preparation example 1

Linked HA in Organic Solvent-Free Aqueous Alkaline Solution

[0067]After 10 g of sodium hyaluronate was mixed with a 1% w / w NaOH aqueous solution, 50 μl of BDDE with respect to 1 g of sodium hyaluronate was added thereto and reacted at about 40° C. for about 3, 12, or 24 hours.

preparation example 2

Linked HA in Ethanol-Containing Aqueous Alkaline Solution (1)

[0068]After 10 g of sodium hyaluronate was mixed with a 1% w / w NaOH aqueous solution containing 10% w / w of ethanol, 50 μl of BDDE with respect to 1 g of sodium hyaluronate was added thereto and reacted at about 40° C. for about 3, 5, 12, or 24 hours.

preparation example 3

Linked HA in Ethanol-Containing Aqueous Alkaline Solution (2)

[0069]After 10 g of sodium hyaluronate was mixed with a 1% w / w NaOH aqueous solution containing 10% w / w of ethanol, 50 μl of EGDGE with respect to 1 g of sodium hyaluronate was added thereto and reacted at about 40° C. for about 24 hours.

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Abstract

Provided are a method of preparing a cross-linked hyaluronic acid having an elasticity of about 50 to about 200 Pa and a viscosity of about 20 to about 100 Pa, including cross-linking hyaluronic acid with an epoxy-based cross-linking agent having at least two epoxy functional groups in an ethanol-containing aqueous alkaline; a method of preparing a cross-linked hyaluronic acid having an elasticity of about 400 to about 800 Pa and a viscosity of about 40 to about 100 Pa, including cross-linking the same cross-linked hyaluronic acid with the same epoxy-based cross-linking agent in an aqueous alkaline solution; and a combination of the cross-linked hyaluronic acids one having an elasticity of about 50 to about 200 Pa and a viscosity of about 20 to about 100 Pa and the other having an elasticity of about 400 to about 800 Pa and a viscosity of about 40 to about 100 Pa.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]This application is a National Phase Application filed under 35 U.S.C. 371 as a national stage of PCT / KR2016 / 005819, filed Jun. 1, 2016, and claims the benefit of Korean Patent Application No. 10-2016-0011843, filed on Jan. 29, 2016, and Korean Patent Application No. 10-2016-0012519, filed on Feb. 1, 2016, in the Korean Intellectual Property Office, the disclosures of which are incorporated herein in their entireties by reference.TECHNICAL FIELD[0002]The present disclosure relates to a preparation method of a cross-linked hyaluronic acid and a combination of cross-linked hyaluronic acids having a viscoelasticity appropriate for use in the living body, comprising the cross-linked hyaluronic acid prepared using the same method.BACKGROUND ART[0003]Hyaluronic acids are a biopolymer material including linearly linked repeating units consisting of N-acetyl-D-glucosamine and D-glucuronic acid, and are also known to be prevalent in animal placenta...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C08B37/08A61K8/73A61K47/36A61L27/20C08J3/24
CPCC08B37/0072A61K8/735A61K47/36A61L27/20C08J3/24C08J2305/08A61K8/0241A61K9/0024A61K9/06A61K47/02A61K47/08A61K47/10A61L2400/06A61L2430/34A61Q19/08A61P17/00A61P19/02C08L5/08C08L2205/025
Inventor CHOI, SUNG CHULKIM, HYUN ILYANG, KI YOUNGPARK, HYO SEUNGLEE, BACK HO
Owner HANMI PHARMA
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