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Insulin carrying microsphere and preparation method thereof

A technology of drug-loaded microspheres and insulin, which is used in pharmaceutical formulations, drug combinations, and non-active ingredients medical preparations, etc. problem, to achieve the effect of improving bioavailability, good pH sensitivity, and achieving release and absorption

Active Publication Date: 2012-04-04
CHANGZHOU INST OF ENERGY STORAGE MATERIALS &DEVICES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Among them, polyacrylic acid materials are easy to synthesize, cheap and easy to obtain, and have the characteristics of enteric solubility. They are widely prepared into hydrogels, microspheres or microspheres coated with other materials. However, acrylic monomers contain double bonds. , the polymer material obtained by its polymerization cannot be biodegraded, and the hydrophilicity of polyacrylic acid is too strong, it is easy to release too much insulin in the gastric juice with low pH value, which reduces the oral bioavailability of this type of preparation
In addition, polyester-based degradable materials such as polylactic acid and polycaprolactone are too hydrophobic and difficult to functionalize, so that their formulations do not have the pH sensitivity required for oral insulin
[0004] Various insulin oral dosage forms and preparation methods thereof are disclosed in the prior art. For example, the Chinese patent document with application number 200410010735.6 discloses a biodegradable polymer microsphere loaded with insulin. The microsphere has a core-shell structure, The core contains nanometer-sized insulin microcrystals, and the shell is made of biodegradable polymer materials. The microspheres are biodegradable, but they are not pH-sensitive, and insulin cannot be released in the stomach but in the intestine. the goal of

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  • Insulin carrying microsphere and preparation method thereof
  • Insulin carrying microsphere and preparation method thereof
  • Insulin carrying microsphere and preparation method thereof

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preparation example Construction

[0041] Correspondingly, the present invention also provides a preparation method of insulin drug-loaded microspheres, comprising the following steps:

[0042] Insulin nanoparticles are placed in the N,N-dimethylformamide (DMF) solution of the polyester amide material with the structure of formula I to form a mixed solution;

[0043] Adding the mixed solution into corn oil, forming an emulsion after shearing and stirring;

[0044] Ether is added to the emulsion, and insulin drug-loaded microspheres are obtained after extraction, and the mass percentage of the insulin nanoparticles in the insulin drug-loaded microspheres is 4-10%, preferably 5-10%, more preferably 6% ~8%,

[0045]

[0046]

[0047] Wherein, x is the molar ratio of the repeating unit of the formula II structure to the repeating unit of the formula III structure, x is 0-0.5, preferably 0.05-0.5, more preferably 0.1-0.4, more preferably 0.2-0.3, n is Polymerization.

[0048]The insulin nanoparticles used i...

Embodiment 1

[0067] After polycondensation of the monomers of the formula IV, the monomers of the formula V and the monocondensation of the formula VI, the benzyl protecting group is removed with hydrobromic acid to obtain a polyester amide polymer material with a large number of carboxyl groups in the side chain.

[0068] The specific experimental steps are:

[0069] 10 mmol, 0.5 mmol and 9.5 mmol of monomers of formula IV structure, formula V structure and formula VI structure were placed in a round bottom flask with magnetic stirring, and dry dimethyl Acetamide (DMA) was dissolved, and after the temperature was raised to 80°C, 3.2mL of dry triethylamine solution was slowly added dropwise, and after 24 hours of polycondensation, it was settled with glacial ethyl acetate and drained;

[0070] Take 1 gram of the initial product obtained by polycondensation of the three monomers and fully dissolve it in 10ml of dichloroacetic acid, add 2ml of hydrobromic acid in 33% acetic acid solution, st...

Embodiment 2

[0072] Place 10 mmol, 2 mmol and 8 mmol of monomers of formula IV structure, formula V structure and formula VI structure respectively in a round bottom flask with magnetic stirring, add dry DMA to dissolve , heated up to 80°C, slowly added dropwise 3.2ml of dry triethylamine solution, reacted for 24 hours, settled with glacial ethyl acetate, and drained;

[0073] Take 1 gram of the initial product obtained by polycondensation of the three monomers and fully dissolve it in 10ml of dichloroacetic acid, add 2ml of hydrobromic acid in 33% acetic acid solution, stir and react at room temperature for 4 hours, and settle the reactant with excess acetone out, and then repeatedly washed with ether and acetone to remove residual hydrobromic acid, and dried in a vacuum oven to obtain the polyester amide material of formula I structure, namely PEA20, and the performance parameters are shown in Table 1.

[0074] The performance parameter of the polyester amide material that table 1 embodi...

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Abstract

The invention discloses an insulin carrying microsphere. A polyesteramide material of which the side chain contains a carboxyl and a hydrophobic isobutyl group at the same time serves as a carrier, wherein the carboxyl endows entericsolubility to the insulin carrying microsphere. Under a strong-acidity environment of gastric juice, because of deprotonation of the carboxyl, the polyesteramide material is not dissolved, the microsphere has certain contractile effect, and then a protein medicament is protected. Under a neutral condition of a small intestine, because of ionization of the carboxyl, the polyesteramide material is gradually dissolved, the microsphere is corroded, and then the wrapped medicament is released. On the other hand, the hydrophobic isobutyl has the effect of regulatingthe pH sensitivity of the material, the hydrophobicity of the insulin carrying microsphere is improved, and the effect with an intestinal cell membrane is enhanced. Therefore, the insulin carrying microsphere has high pH sensitivity, and the releasing and absorption of the insulin in an intestinal tract can be realized.

Description

technical field [0001] The invention relates to the technical field of drug-loaded microspheres, in particular to an insulin drug-loaded microsphere and a preparation method thereof. Background technique [0002] Insulin is a biologically active polypeptide and is the drug of choice for the treatment of diabetes, especially for patients with insulin-dependent diabetes. As a protein and polypeptide drug, insulin has the disadvantages of short half-life and easy destruction in the body, and it is easily destroyed after oral administration, with low bioavailability or even failure. Therefore, the drug is not suitable for direct oral administration, and it is mainly administered in the form of injections clinically. . Since many patients need life-long medication, long-term frequent insulin injections will not only bring considerable physical and mental stress and pain to the patients, but also often cause side effects such as skin redness, itching, infection, and subcutaneous ...

Claims

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Application Information

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IPC IPC(8): A61K9/16A61K38/28A61K47/34C08G69/44A61P3/10
Inventor 陈学思何盼汤朝晖庄秀丽林琳
Owner CHANGZHOU INST OF ENERGY STORAGE MATERIALS &DEVICES
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