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CaP-PLA/PLGA nano-microsphere, and preparation method and application thereof

A PLGA and nano-micro technology, which is applied in pharmaceutical formulations, medical preparations with non-active ingredients, and medical preparations containing active ingredients, etc. less problem

Inactive Publication Date: 2016-02-10
BEIJING YIKEWEI BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although there are many ways to prepare PLA / PLGA microspheres, there are various defects in the properties of the prepared microspheres, such as the uneven particle size of the microspheres, and the inability to accurately control the particle size during the preparation process.
At present, there are few studies on the mineralization of PLA / PLGA microspheres, especially in the process of preparing microspheres, whether it is possible to modify PLA / PLGA microspheres through mineralization to obtain PLA with better properties. / PLGA microspheres, it is unclear

Method used

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  • CaP-PLA/PLGA nano-microsphere, and preparation method and application thereof
  • CaP-PLA/PLGA nano-microsphere, and preparation method and application thereof
  • CaP-PLA/PLGA nano-microsphere, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0083] Preparation of CaP-PLA microspheres

[0084] 1) Dissolve PLA in a mixed oil phase O of dichloromethane and ethyl acetate, the volume ratio of dichloromethane and ethyl acetate is 5:1, and the PLA concentration is 30% mass volume concentration;

[0085] 2) An aqueous solution containing 0.1M calcium ions is used as the internal water phase W 1 , Where the calcium ion comes from calcium chloride;

[0086] 3) The aqueous solution in which PVA is dissolved is used as the outer water phase W 2 , Where the PVA concentration is 5% mass volume concentration;

[0087] 4) Put W 1 Add to O, prepare the primary emulsion W by ultrasonic method 1 / O, where W 1 The volume ratio of O and O is 1:30, and the emulsification time is 2min; this initial emulsion W 1 / O join to W 2 In, the use of mechanical stirring method to prepare pre-multiplex emulsion W 1 / O / W 2 , Where W 1 / O and W 2 The volume ratio is 1:50, and the emulsification time is 5min;

[0088] 5) Then this pre-compound emulsion W 1 / O / ...

Embodiment 2

[0092] Preparation of CaP-PLGA Microspheres

[0093] 1) Dissolve PLGA in the mixed oil phase O of dichloromethane and ethyl acetate, the volume ratio of dichloromethane and ethyl acetate is 8:1, and the PLGA concentration is 45% mass volume concentration;

[0094] 2) An aqueous solution containing 0.1M calcium ions is used as the internal water phase W 1 , Where the calcium ion comes from calcium chloride;

[0095] 3) The aqueous solution in which PVA is dissolved is used as the outer water phase W 2 , Where the PVA concentration is 7% mass volume concentration;

[0096] 4) Put W 1 Add to O, prepare the primary emulsion W by the homogenization method 1 / O, where W 1 The volume ratio of O and O is 1:50, and the emulsification time is 6min; this initial emulsion W 1 / O join to W 2 In, the use of mechanical stirring method to prepare pre-multiplex emulsion W 1 / O / W 2 , Where W 1 / O and W 2 The volume ratio is 1:120, and the emulsification time is 10min;

[0097] 5) Then this pre-compound e...

Embodiment 3

[0100] Adsorption of antigens on CaP-PLA microspheres

[0101] Adsorption of HBsAg by CaP-PLA microspheres Dilute the HBsAg stock solution with pH 6.8 phosphate buffer to a certain concentration, take 1 mL of the diluted HBsAg solution, add a small amount of NaCl to ensure that the antigen solution has a certain salt concentration, and then add 1 mL of the antigen solution Add 5mg of CaP-PLA nanospheres to the HBsAg solution to fully suspend the nanospheres in the HBsAg solution, and vibrate and absorb at a certain temperature for 12h, and the oscillation frequency is 20r / min. At the same time, PLA nanospheres and aluminum salt adjuvant were added to the control experiment.

[0102] Determination of HBsAg adsorption rate Take the mixed solution of antigen microspheres after shaking and adsorption, centrifuge at 5000r / min for 6min, aspirate the supernatant, and use BCA kit and Micro-BCA kit to determine the HBsAg content. The adsorption efficiency (AE) of the microspheres to the an...

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Abstract

The invention provides a method for preparing a CaP-PLA nano-microsphere or CaP-PLGA nano-microsphere medicine preparation through a one-step technology, a CaP-PLA nano-microsphere or a CaP-PLGA nano-microsphere prepared through adopting the method, and an application of the nano-microspheres as an immunoadjuvant. Compared with PLA or PLGA microspheres in the prior art, the nano-microspheres provided by the invention have the advantages of uniform particle size, and facilitation of antigen adsorption due to formation of a large amount of wrinkle structures on the surfaces of the nano-microspheres, and is a good immunoadjuvant. The CaP-PLA nano-microsphere or the CaP-PLGA nano-microsphere prepared in the invention has pH value sensitivity, has large antigen adsorption differences under different pH values, and plays a great role in practical application.

Description

Technical field [0001] The invention relates to a carrier nanosphere and a preparation method thereof, in particular to an application using the nanomicrosphere as an immune adjuvant. Background technique [0002] With the rapid development of genetic engineering and molecular biology technology, large-scale production of proteins, peptide drugs, vaccines, etc. through genetic recombination methods has become possible. Whether used as a therapeutic drug or a preventive vaccine, the protein polypeptide has a short half-life, is easily degraded and inactivated in the body, and requires repeated administration. These characteristics determine that the effect of the protein polypeptide drug alone is not ideal and the drug cost is expensive. In order to solve this problem, scientific and technical personnel began to use drug slow-release or controlled-release technology to embed protein peptides in order to enhance drug efficacy, reduce drug costs, and achieve the purpose of targeted ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/39A61K9/16A61K47/34A61K47/02A61K39/29A61P31/20A61P1/16
Inventor 陈学文林守峰刘玮
Owner BEIJING YIKEWEI BIOTECH CO LTD
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