Exenatide long-acting microsphere preparation and preparation method thereof

A technology of exenatide and microspheres, applied in the field of medicine, can solve problems such as unsatisfactory research results, and achieve the effects of excellent sustained release performance, low burst release rate and low bacterial infection rate

Inactive Publication Date: 2014-09-17
天津新济复兴药业科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the research results are not ideal. Although AC3174 has the biological activity of exenatide, such as lowering blood sugar, delaying gastric emptying and inhibiting the generation of glucagon, etc., its half-life is only 42-43min (exenatide is 90-216min, GLP-1 is 1-5min)

Method used

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  • Exenatide long-acting microsphere preparation and preparation method thereof
  • Exenatide long-acting microsphere preparation and preparation method thereof
  • Exenatide long-acting microsphere preparation and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Different organic solvents of embodiment 1 are used to prepare exenatide PLGA microspheres

[0030] In this example, dimethyl carbonate (DMC), dichloromethane (DCM), and ethyl acetate (Et-Ac) were selected as organic solvents to prepare three groups of microsphere preparations. The formulations of the three groups of microsphere preparations are shown in Table 1. The formula of each microsphere preparation is 10wt% exenatide and 90wt% polyester.

[0031] The type of solvent has a significant impact on the morphology of the product. In this example, exenatide PLGA microspheres were prepared by different organic solvents. The preparation method is as follows (see figure 1 ):

[0032] (1) Weigh 0.1 g of exenatide (1) and 0.9 g of PLGA at the end of the ester group (molecular weight is 40,000, LA / GA=50 / 50);

[0033] (2) Put the PLGA (molecular weight is 40,000, LA / GA=50 / 50) at the end of the ester group in the step (1) into the organic solvent to completely dissolve to ...

Embodiment 2

[0039] Example 2 Preparation of exenatide microspheres of PLGA with different types of ester groups

[0040] This example prepares group 1: the exenatide microsphere preparation of the PLGA (molecular weight is 40,000, LA / GA=50 / 50) of ester group end, group 2: the PLGA (molecular weight is 45,000, LA / GA=50 / 50) of ester group end 75 / 25) exenatide microsphere preparation, the organic solvent used in this embodiment is a mixed solution of dichloromethane (DCM) and dimethyl carbonate (DMC), wherein the exenatide microsphere formulation of Group 1 is 32wt% exenatide and 68wt% polyesters, specifically 0.45g exenatide and 0.97g ester-terminated PLGA (molecular weight 40,000, LA / GA=50 / 50), the preparation method is:

[0041] (1) Weigh 0.45g exenatide and 0.97g ester-terminal PLGA (molecular weight is 40,000, LA / GA=50 / 50) in proportion;

[0042] (2) Put the PLGA (molecular weight is 40,000, LA / GA=50 / 50) in step (1) into dichloromethane (DCM) and dimethyl carbonate (volume ratio is 1: ...

Embodiment 3

[0055] Example 3 Preparation of Exenatide Microspheres with Different Drug Loading Amounts

[0056] In this implementation, three groups of exenatide microspheres with drug loadings of 15.6%, 24.5% and 33.5% were prepared respectively, and the specific formulations are shown in Table 3:

[0057] Table 3: the formula of this embodiment

[0058]

[0059] The concrete preparation method of A preparation is as follows:

[0060] (1) Weigh 0.28g exenatide and 1.5g ester-terminated PLGA (molecular weight is 40,000, LA / GA=50 / 50);

[0061] (2) 1.5g PLGA (molecular weight is 40,000, LA / GA=50 / 50) in the step (1) is dropped into the mixed solution of dichloromethane and dimethyl carbonate and completely dissolved to obtain a clear solution, and then poured into the clear solution Add exenatide and mix and stir evenly to obtain a homogeneous oil solution with a viscosity of 1.76mPa.s;

[0062] (3) The homogeneous oil solution in step (2) is fed into the ultrafine particle preparation...

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Abstract

The invention relates to a preparation method of an exenatide microsphere preparation. The method comprises the steps of: (1) weighing 5-50wt% of exenatide and 95-50wt% of polyester, which is one of or a mixture of PLGA and PLA at an ester group terminal or carboxyl terminal, with the molecular weight of PLGA being 3.0*10<3>-7*10<4> Dalton and the molecular weight of PLA being 4.0*10<3>-7*10<4> Dalton; (2) dissolving the polyester material in an organic solvent completely to obtain a clear solution, then putting exenatide into the clear solution, and conducting mixing and stirring evenly to obtain a homogeneous oil solution; and (3) supplying the homogeneous oil solution into a high speed rotating disc of an ultra-particle preparation system's (UPPS) droplet generation device by a peristaltic pump to form droplets, and curing the droplets to obtain the microsphere preparation. The microsphere preparation prepared by the method has excellent sustained release performance, a drug loading rate of 35%, an encapsulation rate of above 95%, low burst release rate, a sustained release period of more than 2 weeks, and no release lag period.

Description

technical field [0001] The invention relates to the field of medical technology, in particular to a preparation method for obtaining exenatide long-acting microsphere preparations by using an ultrafine particle preparation system (UPPS). Background technique [0002] Exenatide is a new type of antidiabetic drug, which is a synthetic exendin (exendin)-4, which is a natural pancreatic hyperlipidin isolated from the salivary glands of the poisonous lizard distributed in southwestern North America. Glucagon-like peptide-1 (GLP-1) analogs. Exenatide contains 39 amino acid residues, has 53% homology with mammalian GLP-1, is an effective activator of GLP-1 receptors, and has a high affinity with GLP-1R (Exenatide The ability of that peptide to bind to GLP-1R is 2.4 times that of GLP-1), and through the mediation of pancreatic GLP-1R, it exerts a similar blood sugar regulation effect and promotes the secretion of insulin by the pancreas, and the effect of promoting insulin secretio...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/26A61K9/16A61K47/34A61P3/10
Inventor 梁华辉崔景柏张乃军吴传斌
Owner 天津新济复兴药业科技有限公司
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