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Medicine carrying system of polymer micelle and preparation method thereof

A technology of polymer glue and drug-carrying system, applied in pharmaceutical formulations, anti-tumor drugs, drug combinations, etc., can solve the problems of high viscosity, difficulty in wide application, high acetylation, etc. Prepare simple effects

Inactive Publication Date: 2010-09-29
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the high molecular weight, high viscosity and high acetylation of chitosan, it is insoluble in common organic solvents and water, which has caused great difficulties for its wide application.

Method used

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  • Medicine carrying system of polymer micelle and preparation method thereof
  • Medicine carrying system of polymer micelle and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] (1) Preparation of chitosan oligosaccharide

[0031] Take commercially available chitosan (70% degree of deacetylation) with a molecular weight of 550kDa, stir for 2 hours at 55°C and pH5. : 100 (w / w) cellulase (produced by Shanghai Boao Biotechnology Co., Ltd.) was added to degrade chitosan. The degree of degradation of chitosan was controlled by viscosity method. The resulting chitosan degradation solution is filtered to remove impurities, and ultrafiltration is used for fractionation using ultrafiltration membranes with molecular weights of 10 kDa and 30 kDa. The ultrafiltrate with a molecular weight between 10kDa and 30kDa was freeze-dried to obtain chitosan oligosaccharide with a deacetylation degree of 70% and a molecular weight of 18kDa.

[0032] (2) Preparation of salicylic acid-g-chitooligosaccharide graft

[0033]Accurately weigh 0.2756g of carbodiimide (EDC) and 0.0397g of salicylic acid (Salicycleacid, SA) in 3mL of dehydrated ethanol (A solution), then a...

Embodiment 2-4

[0044] Salicylic acid-g-chitooligosaccharide grafts were prepared according to the synthetic recipe shown in Table 1, other conditions were the same as in Example 1, and the test results of physical and chemical properties were shown in Table 2.

[0045] Table 1: The synthetic prescription (n=3) of salicylic acid-g-chitooligosaccharide graft of embodiment 1-4

[0046] Example

Oligochitosan

molecular weight

(kDa)

salicylic acid

theory of

Degree of substitution

EDC (g)

salicylic acid

(g)

ethanol

(ml)

Oligochitosan

(g)

distilled water

(ml)

Example 1

1,8000

50％

0.2756

0.0397

3

0.1

6

Example 2

2,8000

15％

0.0826

0.0119

1

0.1

6

Example 3

2,8000

50％

0.2756

0.0397

3

0.1

6

Example 4

2,8000

100％

0.5512

0.0794

6

0.1

6

...

Embodiment 5-8

[0049] Embodiment 5-8 is loaded with the preparation of paclitaxel micelles

[0050] Accurately weigh 10 mg of the blank salicylic acid-g-chitooligosaccharide carrier material obtained in Examples 1-4 respectively as the raw materials of Examples 5 to 8, and respectively use 10 ml of distilled water to make a 1 mg / ml carrier aqueous solution; Take 10 mg of paclitaxel and dissolve it with 1 ml of ethanol to obtain a 10 mg / ml paclitaxel mother solution. The paclitaxel solution was added to the carrier solution at a drug loading ratio (w / w) of 10%, and the probe was ultrasonicated at 400w for 40 times, working for 2s and resting for 3s. Then the solution was transferred to a dialysis bag (membrane cut-off MWCO=3500) for dialysis to remove ethanol, and the dialysis lasted for 4.5 hours. The dialyzed solution was transferred to a sirloin bottle, and the probe was ultrasonicated again, 400w 40 times, working for 2s and resting for 3s. Centrifuge at 4000rpm for 10min to remove undi...

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Abstract

The invention discloses a polymer micelle medicine carrying system and a preparation method thereof. The polymer micelle medicine carrying system comprises polymer micelles formed by salicylic acid-g-chito-oligosaccharide grafts and at least one non-water soluble drug embedded in the polymer micelles, wherein the non-water soluble drug is a drug, the solubility of which in 1000ml of water medium is equal to or less than 1g. In the invention, the polymer micelles formed by the salicylic acid-g-chito-oligosaccharide grafts are used as a medicine carrier, thereby improving the medicine carrying quantity of non-water soluble drug, and simultaneously the medicine carrying system can control and release the non-water soluble drug under the condition of in vitro leak groove; moreover, the polymer micelle medicine carrying system is simple in preparation and reasonable in process.

Description

(1) Technical field [0001] The invention relates to a polymer micelle drug loading system and a preparation method thereof. (2) Background technology [0002] Most of the anti-tumor chemotherapeutic drugs in clinical application are poorly soluble drugs. Due to their low solubility, it is difficult to dissolve and be absorbed by the body in the water-soluble environment of the human body, and their bioavailability is low. Formulation techniques, including solubilization, solubilization and the use of microparticle drug delivery systems, can improve the solubility of poorly soluble drugs to a certain extent, but existing problems are still prominent, such as the instability of body fluids encountered in the body, and the The toxicity of the applied solubilizing material or solvent, etc. Therefore, designing and synthesizing new drug carriers based on the structure and physical and chemical properties of anti-tumor drugs is one of the key issues to be solved in the realizati...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/36A61K31/337A61K31/704A61K31/4745A61P35/00
Inventor 胡富强魏晓红杜永忠袁弘
Owner ZHEJIANG UNIV
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