Exenatide slow-release microsphere composition and preparation method thereof

A technology of exenatide and sustained-release microspheres, which is applied in the field of exenatide sustained-release microsphere compositions and the preparation thereof, can solve the problems of difficulty in retaining drug activity, complicated preparation process, low encapsulation rate, etc. The effect of avoiding the burst effect, simplifying the preparation process, and avoiding the loss of activity

Active Publication Date: 2016-07-20
SICHUAN KELUN PHARMA RES INST CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The preparation method of exenatide sustained-release microspheres currently reported has problems such as complex preparation process, difficult control, low encapsulation efficiency, and difficulty in retaining drug activity. Therefore, a new preparation method is needed to improve the preparation of microspheres

Method used

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  • Exenatide slow-release microsphere composition and preparation method thereof
  • Exenatide slow-release microsphere composition and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

experiment example 1

[0031] Experimental Example 1 Condition screening test for preparation of exenatide microsphere composition of the present invention (screening of particle size in suspension) 50 mg of exenatide was dissolved in 2 ml of glacial acetic acid, and 0.62 g of purified 50:50DLG3APLGA Dissolve in 9ml of dichloromethane to form a polymer solution, mix the glacial acetic acid solution of exenatide with the dichloromethane solution dissolved in PLGA (polylactic acid-glycolic acid copolymer), and stir the obtained S / O type The particle diameters of the drug particles in the drug suspension were 4 μm, 2 μm, 1 μm, 0.3 μm, and 0.1 μm (the particle size of the suspension was measured by a MalvernZEN1690-nano particle size analyzer), and the other operations were basically the same as in Example 1 to prepare Exena For the peptide sustained-release microspheres, the initial release degrees of the prepared microspheres were 22.6%, 4.7%, 1.32%, 0.86% and 0.63%, respectively. As the particle size...

experiment example 2

[0032] Experimental example 2 Condition screening test (strongly polar solvent screening test) for the preparation of exenatide microsphere composition of the present invention

[0033] Dissolve 20mg of exenatide in 2ml of dimethyl sulfoxide or 2ml of glacial acetic acid or 2ml of N,N-dimethylformamide or 2ml of methanol, and mix it with the dichloromethane solution of PLGA, the particles in the suspension The particle size is 0.3 μm, and other operations are basically the same as in Experimental Example 1. Exenatide slow-release microspheres are prepared, and the encapsulation efficiency of the prepared microspheres is detected by the method for measuring the encapsulation efficiency in (2) in Experimental Example 5. 91.2%, 89.6%, 36.4%, and 42.7%. In order to meet higher encapsulation efficiency, the preferred strong polar solvent is dimethyl sulfoxide and glacial acetic acid, more preferably dimethyl sulfoxide.

experiment example 3

[0034] Experimental Example 3 Condition screening test for preparation of exenatide microsphere composition of the present invention (screening of strong polar solvent / weak polar solvent ratio)

[0035] Taking dimethyl sulfoxide as an example to carry out the screening experiment, dissolving exenatide in different volumes of dimethyl sulfoxide solution, the ratio of dimethyl sulfoxide to methylene chloride solution is 1:5, 1:10 respectively , 1:20, 1:30, 1:40, 1:50, other operations are basically the same as in Experimental Example 2, prepare exenatide sustained-release microspheres, and adopt the in vitro release assay method of (4) in Experimental Example 5 to measure The encapsulation efficiencies of the prepared microspheres were 30.2%, 44.9%, 86.1%, 92.2%, 89.4%, 49.4%, respectively. In order to meet a higher encapsulation efficiency, the preferred volume ratio of dimethyl sulfoxide to dichloromethane solution is 1:20 to 1:40, more preferably 1:30.

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Abstract

The invention provides an exenatide slow-release microsphere composition prepared from an exenatide drug and polymers.The exenatide accounts for 2 %w / w-15 %w / w of the total weight of the microsphere, the polymers are selected from one or more of polycaprolactone, polylactic acid, a polylactic acid-hydroxyacetic acid copolymer and polyanhydride, the particle size of the microsphere ranges from 20 micrometers to 90 micrometers, and the relative biological activity retention rate of the exenatide is higher than 90%.The invention further provides a preparation method of the microsphere composition.According to the preparation method, the problem that the activity losses of the drug on an oil-water interface are caused due to usage of a water phase can be completely avoided on the condition that a protective agent does not need to be added, and the encapsulation rate and the biological activity retention rate of the exenatide are increased; homogeneous turbid liquid or a homogenous solution of submicron drug particles is formed through the solubility differences of the drug in different solvents, micronized drug particles do not need to be prepared, therefore, the preparation technology is simplified, and the burst release effect is avoided.

Description

technical field [0001] The invention relates to the field of pharmaceutical preparations. More specifically, the present invention relates to an exenatide sustained-release microsphere composition and a preparation method thereof. Background technique [0002] Most protein and polypeptide drugs (hereinafter referred to as drugs) have low oral bioavailability and short half-life in blood, and usually require frequent subcutaneous injections to maintain therapeutic levels. Sustained-release microspheres use biodegradable materials (such as polymers) to encapsulate biologically active drugs, control the release of drugs, achieve long-term therapeutic effects, reduce the frequency of administration, and improve patient compliance. [0003] The reported preparation techniques of microsphere preparations of protein and polypeptide drugs include emulsification-solvent evaporation method, coagulation method and spray drying method, etc., among which the W / O / W emulsification-solvent...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/16A61K38/22A61K47/34
Inventor 姚东刚王丹苏正兴赵栋胡思玉王利春王晶翼程志鹏
Owner SICHUAN KELUN PHARMA RES INST CO LTD
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