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Double-phase crosslinked sodium hyaluronate gel with controllable shearing viscosity, and preparation method and preparations thereof

A technology of cross-linking hyaluronic acid and sodium hyaluronate, which is applied in the field of biomedicine, can solve the problems of low shear viscosity and inability to realize viscosity control, and achieve the effect of increasing shear viscosity

Pending Publication Date: 2018-07-06
SHANGHAI LIKANGRUI BIOLOGICAL ENG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] Aiming at the problem that the shear viscosity of biphasic cross-linked sodium hyaluronate gel in the prior art is low and the viscosity cannot be controlled, the present invention aims to provide a biphasic cross-linked sodium hyaluronate gel with controllable shear viscosity. Glue and its preparation method and preparation

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  • Double-phase crosslinked sodium hyaluronate gel with controllable shearing viscosity, and preparation method and preparations thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Example 1: Preparation of two-phase cross-linked sodium hyaluronate gel and gel preparation with controllable shear viscosity.

[0042] Weigh medical sodium hyaluronate (1g, 3.0×10 6 Da), completely dissolved in 0.25M aqueous sodium hydroxide solution (10mL) to obtain an alkaline solution of sodium hyaluronate.

[0043] Under the condition of mechanical stirring, BDDE (0.1 g) was added to the alkaline solution of sodium hyaluronate above, and reacted in a water bath at 40° C. for 3 hours to obtain an alkaline solution of cross-linked sodium hyaluronate.

[0044] Add 0.1M hydrochloric acid to the above alkaline solution of cross-linked sodium hyaluronate and adjust to pH = 7.0, cut the cross-linked sodium hyaluronate mass obtained after neutralization into 1-3 cm 3 The small piece was added to 30 times the weight of PBS buffer (containing 1.587g / L sodium dihydrogen phosphate, 0.528g / L disodium hydrogen phosphate, 7.8g / L sodium chloride, pH=7.2) and dialyzed for 24h, A ...

Embodiment 2

[0047] Example 2: Preparation of two-phase cross-linked sodium hyaluronate gel and gel preparation with controllable shear viscosity.

[0048] Weigh medical sodium hyaluronate (1g, 3.0×10 6 Da), completely dissolved in 0.25M aqueous sodium hydroxide solution (10mL) to obtain an alkaline solution of sodium hyaluronate.

[0049] Under the condition of mechanical stirring, BDDE (0.1 g) was added to the alkaline solution of sodium hyaluronate above, and reacted in a water bath at 40° C. for 3 hours to obtain an alkaline solution of cross-linked sodium hyaluronate.

[0050] Add 0.1M hydrochloric acid to the above alkaline solution of cross-linked sodium hyaluronate and adjust to pH = 7.0, cut the cross-linked sodium hyaluronate mass obtained after neutralization into 1-3 cm 3 The small pieces were added to 20 times the weight of PBS buffer (containing 1.587g / L sodium dihydrogen phosphate, 0.528g / L disodium hydrogen phosphate, 7.8g / L sodium chloride, pH=7.2) and dialyzed for 24h, ...

Embodiment 3

[0053] Example 3: Preparation of two-phase cross-linked sodium hyaluronate gel and gel preparation with controllable shear viscosity.

[0054] Weigh medical sodium hyaluronate (1g, 3.0×10 6 Da), completely dissolved in 0.25M aqueous sodium hydroxide solution (10mL) to obtain an alkaline solution of sodium hyaluronate.

[0055] Under the condition of mechanical stirring, BDDE (0.1 g) was added to the alkaline solution of sodium hyaluronate above, and reacted in a water bath at 40° C. for 3 hours to obtain an alkaline solution of cross-linked sodium hyaluronate.

[0056] Add 0.1M hydrochloric acid to the above alkaline solution of cross-linked sodium hyaluronate and adjust to pH = 7.0, cut the cross-linked sodium hyaluronate mass obtained after neutralization into 1-3 cm 3 The small pieces were added to 20 times the weight of PBS buffer (containing 1.587g / L sodium dihydrogen phosphate, 0.528g / L disodium hydrogen phosphate, 7.8g / L sodium chloride, pH=7.2) and dialyzed for 24h, ...

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Abstract

The invention belongs to the technical field of biological medicine, and relates to a double-phase crosslinked sodium hyaluronate gel with controllable shearing viscosity, and a preparation method andpreparations thereof. The preparation method comprises following steps: 1, dissolving of sodium hyaluronate; 2, crosslinking of sodium hyaluronate; 3, smashing and dialysis of crosslined sodium hyaluronate blocks; and 4, mixing of crosslinked sodium hyaluronate gel with non-crosslinked sodium hyaluronate. The preparation method is capable of increasing product shearing viscosity greatly; the shearing viscosity can be adjusted through adjusting the adding ratio of non-crosslinked sodium hyaluronate; the machinery extruding effect of a colloid mill is capable of realizing entering of non-crosslinked sodium hyaluronate into crosslinked sodium hyaluronate gel particles, so that a three-dimensional net structure of obtained gel finished products is more stable, product elastic modulus is increased at a certain degree, and gel or gel preparations with expected effects are achieved.

Description

technical field [0001] The invention belongs to the field of biomedicine, and relates to a two-phase cross-linked sodium hyaluronate gel with controllable shear viscosity, a preparation method and a preparation thereof. Background technique [0002] Hyaluronic acid (also known as hyaluronic acid) is a linear macromolecular polysaccharide linked by glucuronic acid and N-acetylglucosamine through glycosidic bonds. Under physiological conditions, hyaluronic acid usually exists in the form of sodium salt. Sodium hyaluronate is an important part of the extracellular matrix, and has multiple functions such as regulating immunity, barrier protection, regulating osmotic pressure, and regulating the transport of macromolecular substances. Sodium hyaluronate can be used as an adjuvant drug for ophthalmic surgery and adjuvant treatment for osteoarthritis, and has important physiological functions in wound repair and tissue generation. [0003] Injecting the cross-linked sodium hyalur...

Claims

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Application Information

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IPC IPC(8): C08J3/075C08J3/24C08L5/08A61K9/06A61K47/36A61L27/52A61L27/20
CPCA61K9/06A61K47/36A61L27/20A61L27/52C08J3/075C08J3/24C08J2305/08C08L5/08
Inventor 刘璐吴剑英张军东常臻
Owner SHANGHAI LIKANGRUI BIOLOGICAL ENG
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