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Method For Dissolving Hyaluronic Acid And/or A Salt Thereof

A technology of hyaluronic acid and normal saline, applied in chemical instruments and methods, biochemical equipment and methods, dissolution, etc., can solve problems such as insufficient hyaluronic acid and decrease in molecular weight of hyaluronic acid

Active Publication Date: 2012-12-05
DENKA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] When the present inventors prepare a large amount of liquid containing hyaluronic acid as an injection, they have conducted research on a method for efficiently separating and removing impurities from liquid containing hyaluronic acid to obtain hyaluronic acid of high purity pharmaceutical grade. After repeated studies, it became clear in the course of this study that when dissolving hyaluronic acid in an injection solution, if an ordinary stirring tank is used under normal conditions, the hyaluronic acid will not be dissolved sufficiently to form aggregates, or The molecular weight of hyaluronic acid decreases during dissolution, and the stirring and dissolving process becomes a bottleneck

Method used

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  • Method For Dissolving Hyaluronic Acid And/or A Salt Thereof
  • Method For Dissolving Hyaluronic Acid And/or A Salt Thereof

Examples

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Effect test

Embodiment 1

[0071] 1,580 g of sodium hyaluronate with a molecular weight of 2.37 million obtained by fermentation using Streptococcus equi FM-100 (Weigongyan Junji No. 9027) was filled in a 20 L airtight container with a butterfly valve. Install a dispersing turbine-type stirring paddle in a 200L capacity stainless steel stirring tank with a Teflon coating on the inner surface, add 149L of physiological saline solution (solution for injection) containing 2mM sodium phosphate buffer solution at pH 7.3, and stir groove.

[0072] The airtight container filled with the aforementioned sodium hyaluronate is reversely installed on the raw powder input port of the stirring tank, the butterfly valve is opened, and the sodium hyaluronate is put into the stirring tank. exist Figure 1~2 The figure shows the top view of the dispersing turbine stirring paddles (consisting of 12 paddles with a diameter of 275 mm in the dissolver and 6 paddles with inclined blades).

[0073] Stirring was performed at ...

Embodiment 2

[0080] The configuration of the agitator in the agitation tank was changed variously to find the optimum agitation blade and agitation conditions, and a dissolution test was performed. In the dissolution test, 1580 g of sodium hyaluronate (limited viscosity: 35.0 dL / g) was added to a stirring tank with an inner diameter of 550 mm in which 149 L of physiological saline was added, and the mixer was operated to dissolve it. Regarding the results of the dissolution test, the dispersibility of sodium hyaluronate, whether it can be dissolved, and the decrease in molecular weight were evaluated according to the respective criteria described below.

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Abstract

Disclosed is a method for dissolving hyaluronic acid and / or a salt thereof, in which a stirring tank provided with a stirring blade selected from a turbine-type serrated blade, a dispersion-type serrated blade, a dispersion-turbine-type serrated blade, an anchor-type serrated blade and a paddle-blade equipped serrated blade is used when dissolving hyaluronic acid and / or a salt thereof in an injectable solution selected from injection grade water, physiological saline, and phosphate buffered saline. The method for dissolving hyaluronic acid and / or a salt thereof enables large-scale production of injectable solutions of hyaluronic acid with a molecular weight of 1,500,000 to 4,000,000.

Description

technical field [0001] The present invention relates to a technique for preparing injections of hyaluronic acid and / or its salts (hereinafter collectively referred to as hyaluronic acids) suitable for medicines from a liquid containing hyaluronic acid and / or its salts. Background technique [0002] Hyaluronic acid is a high-molecular-weight polysaccharide with a molecular weight of 5 million, which is a combination of N-acetyl-D-glucosamine and D-glucuronic acid. The disaccharide unit repeats into a chain. Typically, sodium hyaluronate is isolated and purified as the sodium salt formed by the glucuronic acid. Sodium hyaluronate with a molecular weight of about 2 million is known to be more effective as a drug in the treatment of osteoarthritis of the knee, frozen shoulder, and chronic rheumatoid arthritis than sodium hyaluronate with a molecular weight of about 800,000. The effect of (medicine management and treatment Vol.22No.9 289, (1994); medicine management and treatmen...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08B37/08
CPCB01F7/22C08L5/08B01F7/1625B01F7/18B01F7/00225B01F7/00583B01F7/00466C12P19/04C08J3/005C08J2305/08B01F7/162C08B37/0072C08J3/05A61P19/02A61P29/00B01F27/093B01F27/11251B01F27/1152B01F27/13B01F27/81B01F27/808B01F27/91B01F27/90C08B37/00C12M1/06
Inventor 萩原丈士服部裕司星加博光
Owner DENKA CO LTD
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