CN101618021A - Chitosan coating medicine slow release microsphere and preparation method thereof - Google Patents

Abstract

The invention discloses a chitosan coating medicine slow release microsphere and a preparation method thereof. The chitosan coating medicine slow release microsphere comprises a condensate capsule shell of chitosan and glutaric dialdehyde, core medicine resveratrol, oxidative resveratrol, pterostilbene or white cedar alcohol, wherein the core medicine resveratrol, the oxidative resveratrol, the pterostilbene or the white cedar alcohol are coated into the capsule shell. The preparation method is simple and easy, the preparation cost is low, the microsphere envelop rate is 10-50 percent, the microsphere is round and has good dispersivity, the stability of the original medicine is increased, and the chitosan coating medicine slow release microsphere realizes the function of medicine slow control and release and can be conveniently matched with other medicines. The chitosan coating medicine slow release microsphere is suitable for preparing a slow release formulation of medical resveratrol, oxidative resveratrol, pterostilbene and white cedar alcohol.

Description

Chitosan-coated drug sustained-release microspheres and preparation method thereof

technical field

The invention relates to a pharmaceutical preparation and a preparation method thereof, in particular to a chitosan-coated medicine slow-release microsphere and a preparation method thereof.

Background technique

Resveratrol (3,4',5-trihydroxystilbene), oxidized resveratrol (2,4,3',5'-tetrahydroxystilbene), pterostylbene (3 , 5-dimethoxy-4′-hydroxystilbene), picatanol (3,4,3’,5’-tetrahydroxystilbene), which belong to active non-flavonoid polyphenols, widely exist in Among natural foods or plants, a large number of studies have shown that they have significant anti-inflammatory, anti-oxidant, anti-bacterial, anti-free radical and inhibition of platelet aggregation, anti-thrombotic, anti-hyperlipidemia, and can be used for arteriosclerosis, coronary heart disease, viral hepatitis , AIDS, cancer and other diseases prevention and treatment.

Because resveratrol, oxidized resveratrol, pterostilbene, and picatanol contain different numbers of phenolic hydroxyl groups in the molecules, they are easily oxidized in the air, resulting in changes in the color and performance of the product; and the phenolic hydroxyl groups The existence of the above-mentioned several compounds is also susceptible to the influence of pH, and complex changes may occur when they are compounded with other compounds as drugs or health products, affecting their own effective curative effect.

Chitosan (chitosan, CS) is a natural polymer polyaminopolysaccharide obtained after deacetylation of chitin. It has good biocompatibility; it can be biodegraded by various enzymes in the body, and can be Complete absorption; increase the permeability of the drug to the biomembrane, which is conducive to the drug's efficacy in the cell. As a good bio-organic carrier, there are free amino groups on the 2-position of chitosan itself, which can form bond bridge solidified microspheres through aldehyde-ammonia condensation reaction. This property can also be used in sustained-release preparations Research. Sustained-release microspheres are a new dosage form in medicine. The basic principle is to use packaging technology to coat the drug in the capsule material to form a tiny capsule-like preparation, which increases the stability of the drug and is easy to take. At the same time, it achieves the effect of slow and controlled release. Purpose.

Contents of the invention

The technical problem to be solved in the present invention is to provide a kind of chitosan-coated drug slow-release microspheres, the capsule shell is chitosan, and the coated core drug is resveratrol, oxidized resveratrol, pterostilbene or white One of Pitetanol. The slow-release microsphere structure increases the stability of the core drug and can achieve the purpose of slow and controlled release. Chitosan itself also has the characteristics of good biocompatibility, low toxicity, and no hemolysis, which is conducive to the efficacy of drugs.

Another object of the present invention is to provide a preparation method of the above-mentioned sustained-release microspheres, which is simple and feasible, has low preparation cost, and has an encapsulation efficiency of 10-50%.

The present invention will solve above-mentioned technical problem, is achieved by following technical scheme:

A chitosan-coated drug sustained-release microsphere, comprising a capsule shell and a core drug coated in the capsule shell, the capsule shell is a condensation product of chitosan and glutaraldehyde; the core drug is quinoa One of resveratrol, oxidized resveratrol, pterostylbene or piceatanol.

The particle size of the microspheres is 2-100 microns.

The microspheres are round and spherical.

There are pores on the shell wall of the microsphere.

The present invention also provides a preparation method for the above-mentioned chitosan-coated drug slow-release microspheres, which is characterized in that the raw materials for making the active ingredients of the slow-release microspheres are composed of the following parts by weight:

10-30 parts of chitosan, 3-17 parts of glutaraldehyde, 1-9 parts of core medicine;

Wherein the core drug is one of resveratrol, oxidized resveratrol, pterostylbene or piceatanol.

The preparation method is carried out according to the following steps:

(1) Preparation of chitosan acetate solution A

Take chitosan, disperse it into sterilized deionized water, add the aqueous solution of acetic acid, stir evenly, let stand until the air bubbles disappear, and prepare chitosan acetate solution A with a weight-to-volume ratio of 1-5%;

(2) Coating preparation of sustained-release microspheres

Take the core medicine, dissolve it with an alcohol emulsifier, and then add it to solution A, stir evenly to obtain a mixed solution B; add B to the dispersion medium containing an emulsifier, stir to obtain a mixed solution C; take glutaraldehyde to saturate The toluene solution was added to C, and after curing for 5h-10h, centrifuged, washed with petroleum ether, suction filtered, and dried to obtain the product, namely chitosan-coated drug slow-release microspheres.

Described emulsifying agent is the one in sorbitan monostearate Span-80 (Span-80), Span-85 (Span-85), twen-80 (Tween-80), also can It is a mixture of Span-80 (Span-80) and twen-80 (Tween-80).

The dispersion medium is one of soybean oil, olive oil, peanut oil, sunflower oil or liquid paraffin.

The co-emulsifier is one of methanol, ethanol, n-butanol or isopropanol.

In the above technical scheme, the purpose of adding an emulsifier is to make the drug and the dispersion medium form a water-in-oil system, thereby forming small microspheres coated with the drug; the purpose of adding the dispersion medium is to make it act as an oil phase; adding the dispersion medium , on the one hand, the function is to dissolve the drug and fully mix with the system, and on the other hand, it plays an auxiliary role in the formation of microspheres.

The above-mentioned technical scheme adopted in the present invention is to utilize natural polymer polysaccharide chitosan to coat the core drug resveratrol, oxidized resveratrol, pterostilbene or piceatanol to form microspheres with rounded and dispersed properties. good. Due to the advantages of chitosan itself, the drug in the form of microspheres not only improves the stability of the original drug, but also achieves the purpose of slow and controlled release of the drug; in addition, it is convenient to be compatible with other drugs. The preparation method of the slow-release microsphere is simple and easy, the preparation cost is low, the encapsulation efficiency of the prepared microsphere is 10-50%, and the cross-linking agent glutaraldehyde used is glutaraldehyde-saturated toluene solution, which can make the prepared microsphere The surface of the ball is smoother. The preparation method is suitable for the slow-release dosage form of drugs resveratrol, oxidized resveratrol, pterostylbene and piceatanol.

The present invention will be further described in detail below in conjunction with the accompanying drawings and specific embodiments.

Description of drawings

1 is a schematic diagram of the overall structure of the slow-release microspheres of the present invention;

FIG. 2 is a longitudinal sectional view of FIG. 1 .

In the picture: 1. Powdered core drug-resveratrol, oxidized resveratrol, pterostilbene or piceatanol;

2. Shell - the condensation layer of chitosan and glutaraldehyde;

3. Pores; 4. Wrinkles.

Detailed ways

Embodiment 1-6 is respectively the sustained-release microspheres of different medicines coated with chitosan and preparation method thereof

The structure of each slow-release microsphere is shown in Fig. 1 and Fig. 2, including a spherical capsule shell 2 and a powdery core medicine coated in the capsule shell 2. The capsule shell is a condensation product of chitosan and glutaraldehyde, and the core drug components are resveratrol, oxidized resveratrol, pterostilbene, piceatanol, resveratrol, oxidized resveratrol .

The microsphere is a rounded sphere with a particle size of 2-100 microns, the surface is not smooth, with wrinkles 4, and there are pores 3 on the shell wall.

In embodiment 1-embodiment 6, the ratio of raw materials for making the active ingredients of sustained-release microspheres is shown in the table. The preparation method of sustained-release microspheres is carried out according to the following steps:

(1) configure chitosan solution

Weigh chitosan to disperse in sterilized deionized water, then add acetic acid solution, stir evenly, let stand until bubbles disappear, and prepare chitosan solution A with a weight-to-volume ratio of 1-5%;

(2) Coating preparation of sustained-release microspheres

Take the drug resveratrol, oxidized resveratrol, pterostilbene or picatanol, dissolve it with an alcohol co-emulsifier, then add it to the A solution prepared in the previous step, and stir evenly to obtain a mixed solution B; B was added to the dispersion medium containing emulsifier, stirred to obtain mixed liquid C; another toluene solution saturated with glutaraldehyde was added to C, after solidification for 5h-10h, centrifuged, washed with petroleum ether, suction filtered, and dried to obtain The product is chitosan-coated slow-release microspheres of resveratrol, oxidized resveratrol, pterostylbene or piceatanol.

For example, the preparation method of slow-release microspheres in Example 1 is carried out in the following steps:

(1) configure 3% chitosan (CS) solution

Weigh 1.5g of chitosan and disperse it in 47mL of sterilized distilled water, then add 3mL of 36% acetic acid, stir evenly, let stand until the bubbles disappear, and obtain 3% (W/V) CS solution A.

(2) Preparation of chitosan-coated resveratrol (3,4',5-trihydroxystilbene) sustained-release microspheres

Take 2mL of the solution A obtained in the previous step and add it into a small beaker; respectively take 0.5g of the raw material resveratrol (3,4',5-trihydroxystilbene), dissolve it with a small amount of ethanol (as an emulsifier) and add it to In a small beaker, stir evenly to obtain mixed solution B; then add B to 15 mL of Span-80 (a sorbitan monostearate emulsifier, Span-80) containing 5% (W/V) Stir in soybean oil (as a dispersion medium) to obtain mixture C; add 1 mL of 50% glutaraldehyde-saturated toluene solution (containing about 1 g of glutaraldehyde) to C, and solidify for 6 hours; separate by centrifuge, and use petroleum ether Wash, filter with suction, and dry to obtain the product with an encapsulation efficiency of 50% and a particle size of 6.3 μm.

Claims (9)

1, a kind of chitosan coating medicine slow release microsphere comprises softgel shell, is coated on the medicine in the softgel shell, and it is characterized in that: described softgel shell is the condensation substance of chitosan and glutaraldehyde; Described core medicine is a kind of in resveratrol, oxidized resveratrol, Lignum pterocarpi indici Stilbene or the Rhizoma Euonymus China fir alcohol.

2, chitosan coating medicine slow release microsphere according to claim 1 is characterized in that: microspherulite diameter is the 2-100 micron.

3, chitosan coating medicine slow release microsphere according to claim 1 is characterized in that: described microsphere is the sphere of rounding.

4, chitosan coating medicine slow release microsphere according to claim 1 is characterized in that: have hole on the described microsphere shell wall.

5, a kind of preparation method as each described chitosan coating medicine slow release microsphere among the claim 1-4 is characterized in that making the sustained-release micro-spheres raw materials of effective components and forms according to following parts by weight:

Chitosan 10-30 part, glutaraldehyde 3-17 part, core medicine 1-9 part;

Wherein said core medicine is a kind of in resveratrol, oxidized resveratrol, Lignum pterocarpi indici Stilbene or the Rhizoma Euonymus China fir alcohol.

6, the preparation method of chitosan coating medicine slow release microsphere according to claim 5 is characterized in that described preparation method carries out according to following sequence of steps:

(1) preparation acetic acid chitosan solution A

Get chitosan, be distributed in the sterilization deionized water, add acetic acid water solution again, stir, leave standstill and treat the bubble cancellation, making w/v is the acetic acid chitosan solution A of 1-5%;

(2) coat the preparation sustained-release micro-spheres

Get the core medicine,, join then in the solution A, stir, get mixed liquid B with the dissolving of alcohols co-emulsifier; B joins in the disperse medium that contains emulsifying agent, stirs, and gets mixed liquor C; Get the saturated toluene solution of glutaraldehyde and add among the C, behind the curing 5-10h, centrifugalize, petroleum ether cleans, sucking filtration, drying gets product, i.e. chitosan packaging medicine sustained-release micro-spheres.

7, chitosan bag according to claim 6 is carried out the preparation method of medicament slow-release microsphere, it is characterized in that: described emulsifying agent is a kind of among sorbitan monostearate Span-80, Span-85, the twen-80, also can be the mixture of Span-80 and twen-80.

8, the preparation method of chitosan coating medicine slow release microsphere according to claim 6 is characterized in that: described disperse medium is a kind of in soybean oil, olive oil, Oleum Arachidis hypogaeae semen, sunflower oil or the liquid paraffin.

9, the preparation method of chitosan coating medicine slow release microsphere according to claim 6 is characterized in that: described alcohols co-emulsifier is a kind of in methanol, ethanol, n-butyl alcohol or the isopropyl alcohol.

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