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Silk fibroin modified depression structure lactic acid-based polymer drug-carrying microsphere and method for preparing same

A technology of drug-loaded microspheres and silk fibroin, which is applied in the field of biomedicine, can solve the problems of disintegration of drug-loaded particles, destruction of sustained-release preparations, dissolution of hydrophobic drugs, etc. Compatibility effect

Inactive Publication Date: 2017-02-22
STOMATOLOGICAL HOSPITAL TIANJIN MEDICAL UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, for hydrophobic drugs such as statins, such as simvastatin, which are easily soluble in organic solvents such as ethanol, the use of high-concentration methanol or ethanol solvents can easily lead to the dissolution of hydrophobic drugs, and even the disintegration of drug-loaded particles, destroying the sustained release preparation
Therefore, the modification of the surface of silk fibroin by direct cross-linking of glutaraldehyde on the pit-structured lactic acid-based polymer microspheres loaded with hydrophobic drugs, and its application in topical drug sustained-release preparations has not been reported.

Method used

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  • Silk fibroin modified depression structure lactic acid-based polymer drug-carrying microsphere and method for preparing same
  • Silk fibroin modified depression structure lactic acid-based polymer drug-carrying microsphere and method for preparing same
  • Silk fibroin modified depression structure lactic acid-based polymer drug-carrying microsphere and method for preparing same

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Embodiment 1: the preparation of silk fibroin aqueous solution:

[0041] Take 1g of silk fibroin powder, place it in 5mL LiBr (9.3M) aqueous solution, stir slowly at 60°C for 4h to produce a 20% solution, transfer the resulting solution to a dialysis bag (MWCO 3500), and dialyze with distilled water for 4d (change the water every 4h Once), the obtained solution was centrifuged at 8,000 rpm for 20 min, and repeated 3 times to remove insoluble matter, and then the obtained solution was passed through a 0.45 μm filter membrane. By measuring the weight of a certain volume of the silk fibroin aqueous solution after freeze-drying, the concentration of the silk fibroin aqueous solution is about 3%. And dilute it into a silk fibroin aqueous solution with a concentration of 0.5%-2%, and store the stock solution at 4°C for use.

Embodiment 2

[0043] Dimple structure lactic acid-based polymer microspheres are made by the following method:

[0044] (1) Dissolving the lactic acid-based polymer in dichloromethane to make a solution 1 with a concentration of 10 mg / mL;

[0045] (2) Add solution 1 to a 1% polyvinyl alcohol aqueous solution with a mass concentration of 1% at a stirring speed of 800 rpm, and the volume ratio of the solution 1 to the polyvinyl alcohol aqueous solution is 1:5;

[0046] (3) Continue to stir for 3 hours, centrifuge, remove the supernatant, wash with deionized water, and freeze-dry to obtain lactic acid-based polymer microspheres with pit structure.

[0047] The lactic acid-based polymer is a polylactic acid-glycolic acid copolymer with a weight average molecular weight of 10,000–50,000.

[0048] The yield of the obtained pit-structured lactic acid-based polymer microspheres was 82%. The SEM pictures of the microspheres are shown in figure 1 , its shape is spherical, the diameter is 6.8-29.3μ...

Embodiment 3

[0050] Dimple structure lactic acid-based polymer microspheres are made by the following method:

[0051] (1) Dissolving the lactic acid-based polymer in dichloromethane to make a solution 1 with a concentration of 5 mg / mL;

[0052] (2) Add solution 1 to a 0.5% polyvinyl alcohol aqueous solution with a stirring speed of 400 rpm, and the volume ratio of the solution 1 to the polyvinyl alcohol aqueous solution is 1:10;

[0053] (3) Continue to stir for 2 hours, centrifuge, remove the supernatant, wash with deionized water, and freeze-dry to obtain lactic acid-based polymer microspheres with a pit structure.

[0054] The lactic acid-based polymer is a polylactic acid-glycolic acid copolymer with a weight average molecular weight of 10,000–50,000.

[0055] Yield and shape were similar to Example 2.

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Abstract

The invention discloses a silk fibroin modified depression structure lactic acid-based polymer drug-carrying microsphere and a method for preparing the same. The method includes (1), dissolving a lactic acid-based polymer in dichloromethane to obtain solution 1; (2), mixing a hydrophobic drug and the solution 1 to obtain solution 2; (3), adding the solution 2 into polyvinyl alcohol aqueous solution under stirring; (4), continuing to stir, centrifuging, removing supernatant, washing with deionized water and carrying out freeze-drying to obtain a lactic acid-based polymer drug-carrying microsphere with depression structure; (5), uniformly mixing silk fibroin aqueous solution and the lactic acid-based polymer drug-carrying microsphere with depression structure to obtain a mixture, centrifuging, removing supernatant, adding glutaraldehyde aqueous solution, carrying out cross-linking, centrifuging, and carrying out freeze-drying. The lactic acid-based polymer drug-carrying microsphere and the method have the advantages that particle size of the lactic acid-based polymer drug-carrying microsphere is uniformly distributed, the method is simple and convenient, the lactic acid-based polymer drug-carrying microsphere is stable in structure, a drug can be slowly released, the hydrophilic properties of the surface of the drug and the structural strength of material can be improved by silk fibroin membrane on the surface of the drug, the release rate can be effectively reduced, and the release time can be prolonged.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to pit-structured lactic acid-based polymer microspheres, pit-structured lactic acid-based polymer drug-loaded microspheres and silk fibroin-modified pit-structured lactic acid-based polymer drug-loaded microspheres. Background technique [0002] Degradable polymeric drug carriers have received more and more attention in the field of systemic and local drug delivery, and the surface modification of drug carriers by physical adsorption or self-assembly methods can further endow them with unique physical, chemical and biological properties. . For example, polylysine modification on the surface of albumin nanoparticles can effectively inhibit the degradation of enzymes (Singh, H.D.; Wang, G.; Uludag, H.; Unsworth, L.D. Acta Biomater 2010, 6, 4277); In drug administration, the drug release stability and drug permeability of liposomes modified by silk fibroin or chitosan surface have been sig...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/34A61K47/42A61K9/16
CPCA61K9/1641A61K9/1658
Inventor 乔峰张俊江周志敏
Owner STOMATOLOGICAL HOSPITAL TIANJIN MEDICAL UNIV
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