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Physical cross-linking hydrogel composition and preparation method and application thereof

A physical cross-linking and hydrogel technology, which is applied in the fields of polymer materials and medicine, can solve the problems that the gelation temperature is not suitable for human body application, no longer has heat-sensitive gelation, and loses sol-gel transition. To achieve the effect of facilitating medical application, expanding the scope of use, and good biocompatibility

Active Publication Date: 2013-04-10
上海复凝科技有限公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0009] (1) Exceeding a certain composition and / or molecular weight, it can only be completely dissolved in water or partially or completely become precipitated, thereby losing the sol-gel transition and no longer having the relevant heat-sensitive gelling performance;
[0010] (2) In addition, even if some polymers can show heat-sensitive properties, their gelation temperature is not suitable for human application;
[0011] (3) The adjustment range and kinetic process of its degradation rate have certain limitations, which limits its medical use

Method used

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  • Physical cross-linking hydrogel composition and preparation method and application thereof
  • Physical cross-linking hydrogel composition and preparation method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0065] Add PEG (1500) in a 250ml three-necked flask, heat the oil bath to 150°C, and vacuum filter for three hours under stirring to remove the residual moisture in the PEG, then add DL-lactide and After glycolide was heated under vacuum to make it melt completely, 120 μl of stannous octoate was added, the temperature of the oil bath was raised to 160° C., and the reaction was continued for 24 hours under an argon atmosphere. After the reaction was completed, vacuum filtration was performed for two hours to remove unreacted monomers and low-boiling products. The initial product was dissolved in dichloromethane solution and precipitated with ether, the yield was about 80%. Measure the number-average and weight-average molecular weight (M) of the BAB block copolymer (PLGA-PEG-PLGA, Copolymer-1) by gel permeation chromatography (GPC) (using polystyrene as a standard sample). n ,M w ) are 5510 and 6390 respectively, molecular weight distribution coefficient (M w / M n ) is 1.16...

Embodiment 2

[0067] Add single-ended methoxypolyethylene glycol MPEG (550) into a 250ml three-necked flask, heat the oil bath to 150°C, and vacuum filter for three hours under stirring to remove residual moisture in MPEG, and then add a molar ratio of 3 : 1 DL-lactide and glycolide, heated under vacuum to make it completely melted, then added 120 μl of stannous octoate, the oil bath was heated to 160° C., and the reaction was continued for 24 hours under an argon atmosphere. After the reaction was completed, vacuum filtration was performed for two hours to remove unreacted monomers and low-boiling products. The initial product was dissolved in dichloromethane solution and precipitated with ether, the yield was about 85%. Measure the number-average and weight-average molecular weight (MPEG-PLGA, Copolymer-14) of the BA block copolymer (MPEG-PLGA, Copolymer-14) by gel permeation chromatography (GPC) (using polystyrene as a standard sample). n ,M w ) are 3550 and 4620 respectively, molecula...

Embodiment 3

[0069] Add polyethylene glycol (1000) and PLGA (M n 4750, M w 6020, a mixture of LA / GA=1 / 1), heated under vacuum to melt completely, then the oil bath was heated to 160°C for condensation reaction for 18 hours. After the reaction is complete, the initial product is dissolved in dichloromethane solution and precipitated with a large amount of ether, and the yield is about 85%. Measure the number average and weight average molecular weight (M) of the BAB block copolymer by gel permeation chromatography (GPC) (using polystyrene as a standard sample). n ,M w ) are 6520 and 8340 (PLGA-PEG-PLGA, Copolymer-15) respectively, molecular weight distribution coefficient (M w / M n ) is 1.28. The copolymer itself does not have the property of thermally reversible gelation in water.

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Abstract

The invention belongs to the technical field of macromolecular materials and medicaments, and relates to a physical cross-linking hydrogel composition and a preparation method and application thereof. The composition is a mixture of two or more polymers, and the aqueous system of the composition has the temperature-sensitive reversible gelling property; when the temperature is lower than a sol-gel conversion temperature, the mixture can be dissolved in water; and when the temperature is higher than the sol-gel conversion temperature, the aqueous solution of the mixture forms gel, and the process is reversible, wherein the polymers comprise a block copolymer consisting of polyethylene glycol serving as a hydrophilic block and degradable polyester serving as a hydrophobic block. The aqueoussolution of the composition can be applied to warm-blooded animals through non-stomach intestinal tract, eye, subcutaneous, muscle, vagina, urethra, nasal cavity or lung, forms gel at physiological related temperature, and also can be applied in a gel form. The release speed can be regulated by changing the mixing proportion, polymer composition, molecular weight and polydispersity.

Description

technical field [0001] The invention belongs to the technical field of polymer materials and medicine, and relates to a physically cross-linked hydrogel composition and a preparation method thereof, in particular to a physically cross-linked hydrogel with thermally reversible gel performance and a preparation method thereof, and the Applications of hydrogels in parenteral, eye, subcutaneous, intramuscular administration, etc. Background technique [0002] In recent years, with the development of biotechnology and genetic engineering, many peptide / protein drugs with pharmacological activity have been commercialized. However, peptide or protein drugs are easily degraded by digestive enzymes in the gastrointestinal tract, and their biological half-life is short, which makes their administration routes relatively limited. Generally, they can only be administered through intravenous, intramuscular, or subcutaneous injections. Studies have shown that in conventional solvents, pep...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/34A61K9/00
Inventor 丁建东俞麟
Owner 上海复凝科技有限公司
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