Protein polypeptide medicine duplex microsphere, preparation method of protein polypeptide medicine duplex microsphere, and insulin duplex microsphere

A technology of protein polypeptide and insulin, which is applied in drug combination, drug delivery, pharmaceutical formulation, etc., can solve the problems of lower encapsulation rate, obvious burst release effect, toxic and side effects, etc., achieve compact texture of microspheres, reduce burst release effect, The effect of uniform particle size

Active Publication Date: 2019-04-05
JILIN HUISHENG BIOPHARMACEUTICAL CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In the past, chitosan (CS)-polylactic acid-glycolic acid copolymer (PLGA) double microspheres were used to encapsulate insulin in oral insulin microsphere preparations, but most of them had low encapsulation efficiency and obvious burst release effect.
Encapsulation rate and burst release rate are two important indicators for evaluating a microsphere. A lower encapsulation rate cannot reach the predetermined therapeutic dose, while a higher burst rate will cause serious toxic side effects.
Although reduced burst release can be achieved by preparing microspheres with low encapsulation efficiency, reducing encapsulation efficiency often does not achieve therapeutic doses

Method used

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  • Protein polypeptide medicine duplex microsphere, preparation method of protein polypeptide medicine duplex microsphere, and insulin duplex microsphere
  • Protein polypeptide medicine duplex microsphere, preparation method of protein polypeptide medicine duplex microsphere, and insulin duplex microsphere
  • Protein polypeptide medicine duplex microsphere, preparation method of protein polypeptide medicine duplex microsphere, and insulin duplex microsphere

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] 1. Dissolve 0.01g of recombinant human insulin raw material and 20.00g of chitosan (CS) successively in 150mL of acetic acid solution with a pH of 5.0, and stir for 0.5h; Use water for injection as the exchange liquid to treat the above mixture for 4 cycles, discard the permeate each time, collect the reflux liquid, and then process the collected reflux liquid with a 30KD molecular weight membrane filtration system to collect nanospheres that meet the predetermined molecular weight Permeate; Finally, the collected permeate was centrifuged for 30min, the supernatant was discarded, the resulting precipitate was poured into a plate, and dried under reduced pressure at 4°C for 4h to obtain insulin-chitosan ( CS) nanoparticle solid powder.

[0042] 2. Dissolve 20.00g of polylactic acid with a molecular weight of 10000Da in acetonitrile, then add this solution to 150mL of acetate buffer solution with a pH of 5.0 and stir evenly, add 20mL to the buffer system (according to the...

Embodiment 2

[0048] 1. Dissolve 1.00g insulin aspart raw material drug and 20.00g chitosan (CS) successively in 150mL acetic acid solution with pH 5.0, and stir for 8h; The above mixture was treated for 6 cycles, and the permeate was discarded each time, and the reflux was collected, and then the collected reflux was treated with a membrane filtration system with a molecular weight of 30KD, and the nanosphere permeate that met the predetermined molecular weight was collected; finally, the The collected permeate was centrifuged for 30 minutes, the supernatant was discarded, the obtained precipitate was poured into a plate, and dried under reduced pressure at 4° C. for 10 hours to obtain insulin-chitosan (CS) nanoparticle solid powder.

[0049] 2. Dissolve 10.00 g of polylactic acid with a molecular weight of 10,000 Da in acetonitrile, then add this solution to 150 mL of acetate buffer solution with a pH of 5.0 and stir evenly, and add 3.4 mL (according to the density of 1.0×10 3 kg / m 3 Cal...

Embodiment 3

[0054] 1. Preparation of insulin degludec microspheres: Dissolve 1.00 g of insulin degludec raw material in 0.1 mol / L hydrochloric acid, stir until completely dissolved, and use a high-pressure homogenizer to repeatedly homogenize the obtained insulin solution to a nanometer After the particle size distribution of about 80% or more is 100nm as measured by a laser particle size analyzer, the insulin degludec microsphere powder is obtained by freeze-drying.

[0055]2. Dissolve 1.00 g of the insulin degludec microspheres and 20.00 g of chitosan (CS) successively in 150 mL of acetic acid solution with a pH of 5.0, and stir for 12 hours; first use a membrane filtration system with a molecular weight of 10KD, and use water for injection as an exchange The above mixture was treated with liquid for 8 cycles, the permeate was discarded each time, and the reflux liquid was collected, and then the collected reflux liquid was treated with a membrane filtration system with a molecular weigh...

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Abstract

The invention provides a protein polypeptide medicine duplex microsphere and a preparation method thereof. The method comprises the following steps of S1, performing medicine loading on protein polypeptide medicine and chitosan in weak acidic solvents; obtaining a nanometer particle solution; sequentially performing film filtering and reduced pressure drying to obtain the medicine coated chitosannanometer particles; S2, under the effect of coupling agents, performing grafting reaction on the medicine coated chitosan nanometer particles and polylactic acid to obtain the protein polypeptide medicine duplex microsphere. The invention also provides an insulin duplex microsphere, which is prepared by the method. The insulin duplex microsphere has the advantages that the use is safer; the patient tolerance is better; the effect is longer; the medicine effect is more stable; the sudden release is obviously reduced.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical preparations, in particular to a protein-polypeptide drug double microsphere, a preparation method thereof, and an insulin double microsphere. Background technique [0002] Insulin is a protein macromolecular drug with poor stability and low bioavailability, and it is not easy to be directly absorbed through oral administration. Therefore, injection is still the main route of insulin administration. However, the insulin injection route requires frequent administration, which is not only inconvenient but also painful for patients with chronic diseases, and the patient's compliance is poor. In the process of practical application, injection administration is also prone to adverse reactions such as induration at the injection site and subcutaneous fat atrophy. In addition, studies have shown that there is a big difference between the way of injection and the secretion of insulin in the body u...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K47/59A61K38/28A61P3/10
CPCA61K38/28A61K47/593A61K47/6939A61P3/10
Inventor 曹海燕赵阳逯子毅纪凤南顾志强于平曲瑞杨利
Owner JILIN HUISHENG BIOPHARMACEUTICAL CO LTD
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