CN101543477A - Sustained-release microsphere of chitosan-coated 3,5-dihydroxy-4-isopropyl toluylene and preparation method thereof - Google Patents
Sustained-release microsphere of chitosan-coated 3,5-dihydroxy-4-isopropyl toluylene and preparation method thereof Download PDFInfo
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- CN101543477A CN101543477A CN200910074292A CN200910074292A CN101543477A CN 101543477 A CN101543477 A CN 101543477A CN 200910074292 A CN200910074292 A CN 200910074292A CN 200910074292 A CN200910074292 A CN 200910074292A CN 101543477 A CN101543477 A CN 101543477A
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Abstract
The invention discloses a sustained-release microsphere of chitosan-coated 3,5-dihydroxy-4-isopropyl toluylene and a preparation method thereof. The microsphere has a core-shell structure, wherein the core is a powdered 3,5-dihydroxy-4-isopropyl toluylene layer, and the shell is a cross-linking condensate layer of chitosan and glutaraldehyde. The sustained-release microsphere is prepared from a chitosan-coated medicament of 3,5-dihydroxy-4-isopropyl toluylene, and the prepared microsphere can improve the stability of the medicament, improve the skin permeability at the same time, and achieve the aim of slow release of the medicament; the capsule shell has the characteristics of good biocompatibility, low toxicity, no hemolysis and the like, and is advantageous for the medicament to exert the curative effect; and the preparation method is simple, the preparation cost is low, and the product encapsulation rate is between 10 and 36 percent, thus the method is applicable to processing the sustained-release microsphere of the medicament of 3,5-dihydroxy-4-isopropyl toluylene.
Description
Technical field
The present invention relates to a kind of pharmaceutical preparation and preparation method thereof, specifically a kind of chitosan coats 3, sustained-release micro-spheres of 5-dihydroxy-4-isopropyl toluylene and preparation method thereof.
Background technology
3,5-dihydroxy-4-isopropyl toluylene (medicine name: benzene alkene is moral not) has good antifungal activity, can be used for treating diseases such as intractable psoriasis.The existing dosage form of this medicine is mainly ointment, many with 3, the solid amorphous powder preparation of 5-dihydroxy-4-isopropyl toluylene, because 3, the poor stability of 5-dihydroxy-4-isopropyl toluylene molecule itself, easily oxidized in air, cause the color of product and performance that great change takes place; And this compound water-soluble degree of separating is low, makes percutaneous permeability poor.
(Chitosan is by the poly-aminopolysaccharide of a kind of natural polymer that obtains behind the chitin deacetylase base CS) to chitosan, has bioadhesive and multiple biological activity, and good biocompatibility can be absorbed by organism fully by plurality of enzymes biodegradation in the body; Simultaneously, chitosan can also increase medicine to biomembranous permeability, helps medicine and bring into play drug effect better in cell.
Chitosan is as a kind of good biological organic carrier, on 2 of its molecules free amine group is arranged, can make it to form key bridge solidified microsphere by the aldehyde ammonia condensation reaction, also having it is a unique chemical compound that has positive charge in the natural macromolecular material, also can utilize this character to be applied to the research of slow releasing preparation, be used for packaging medicine so chitosan itself can be used as a kind of carrier, have wide researching value.
Sustained-release micro-spheres is a kind of novel form in the medicine, also is the new trend of pharmaceutical dosage form development, is to utilize technique for packing that pharmaceutical pack is overlayed on the small cryptomere preparation of formation in the capsule material, can increase product stability, and then reaches the purpose of slow controlled release.
Summary of the invention
The technical issues that need to address of the present invention provide a kind of medicine 3, novel form-the sustained-release micro-spheres of 5-dihydroxy-4-isopropyl toluylene, sustained-release micro-spheres is to utilize chitosan coating medicine 3,5-dihydroxy-4-isopropyl toluylene is made, can improve stability of drug, improve percutaneous permeability, can reach purpose simultaneously medicine sustained and controlled release; Softgel shell has good biocompatibility, and toxicity is low, and characteristics such as haemolysis do not help medicine performance curative effect.
Another object of the present invention provides the preparation method of above-mentioned sustained-release micro-spheres, this method simple possible, and envelop rate is 10%～36%.
It is to be achieved by following technical scheme that the present invention will solve above-mentioned technical problem:
A kind of chitosan coats 3, and the sustained-release micro-spheres of 5-dihydroxy-4-isopropyl toluylene, microsphere are nucleocapsid structure, and its center is Powdered 3, and 5-dihydroxy-4-isopropyl toluylene layer, shell are the crosslinked condensation substance layer of chitosan and glutaraldehyde.
Described microsphere is spherical.
Described microspherulite diameter is the 0.1-100 micron.
The present invention also provides above-mentioned chitosan to coat 3, and the preparation method of the sustained-release micro-spheres of 5-dihydroxy-4-isopropyl toluylene, described sustained-release micro-spheres raw materials of effective components comprise following parts by weight composition:
10-30 parts of chitosans,
3,1-9 parts of 5-dihydroxy-4-isopropyl toluylene,
10-50 parts of glutaraldehydes;
This preparation method is carried out according to following sequence of steps:
(1) configuration chitosan solution
Take by weighing chitosan and disperse to add acetic acid solution again in the sterilization deionized water, stir, leave standstill and treat the bubble cancellation, make w/v and be 1～5% configuration chitosan solution A;
(2) coat the preparation sustained-release micro-spheres
The thing 3 of getting it filled, 5-dihydroxy-4-isopropyl toluylene with the alcohols solvent dissolving, joins in the made A solution of step then, stirs, must mixed liquid B; B is joined in the disperse medium that contains emulsifying agent, stir, get mixed liquor C; Other gets among the glutaraldehyde solution adding C, behind curing 4h～8h, and centrifugalize, petroleum ether cleans, sucking filtration, drying promptly gets the product chitosan and coats 3, the sustained-release micro-spheres of 5-dihydroxy-4-isopropyl toluylene.
Described emulsifying agent is a kind of among sorbitan monostearate Span-80 (Span-80), Span-85 (this dish-85) or the twen-80 (tween 80).
Described disperse medium is a kind of in soybean oil, olive oil, Oleum Arachidis hypogaeae semen, sunflower oil or the liquid paraffin.
Described alcohols solvent is a kind of in methanol, ethanol, n-butyl alcohol or the isopropyl alcohol.
Sustained-release micro-spheres provided by the present invention utilizes chitosan coating medicine 3, and 5-dihydroxy-4-isopropyl toluylene is made, and can improve stability of drug, improves percutaneous permeability, can reach the purpose to medicine sustained and controlled release simultaneously; Softgel shell has good biocompatibility, and toxicity is low, and characteristics such as haemolysis do not help medicine performance curative effect.Its preparation method is simple, and preparation cost is low, and product packaging rate 10～36% is suitable for processing medicine 3,5-dihydroxy-4-isopropyl toluylene be the sustained-release micro-spheres of softgel shell with the chitosan.
The present invention is described in further detail below in conjunction with Figure of description and specific embodiment.
Description of drawings
Fig. 1 is the cross-sectional view of sustained-release micro-spheres of the present invention.
The specific embodiment
A kind of chitosan as shown in Figure 1 coats 3, the spherical sustained-release micro-spheres of 5-dihydroxy-4-isopropyl toluylene is nucleocapsid structure, and its center 1 is Powdered 3,5-dihydroxy-4-isopropyl toluylene layer, softgel shell are the crosslinked condensation substance layer of chitosan and glutaraldehyde.
The preparation method of this sustained-release micro-spheres is carried out according to following sequence of steps:
(1) configuration chitosan solution
Take by weighing chitosan and disperse to add acetic acid solution again in the sterilization deionized water, stir, leave standstill and treat the bubble cancellation, make w/v and be 1～5% configuration chitosan solution A;
(2) coat the preparation sustained-release micro-spheres
The thing 3 of getting it filled, 5-dihydroxy-4-isopropyl toluylene with the alcohols solvent dissolving, joins in the made A solution of step then, stirs, must mixed liquid B; B is joined in the disperse medium that contains emulsifying agent, stir, get mixed liquor C; Other gets among the glutaraldehyde solution adding C, behind curing 4h～8h, and centrifugalize, petroleum ether cleans, sucking filtration, drying promptly gets the product chitosan and coats 3, the sustained-release micro-spheres of 5-dihydroxy-4-isopropyl toluylene.
The related data of each embodiment such as following table in the preparation method:
Wherein the preparation method specific operation process of embodiment 1 is as follows:
(1) chitosan (CS) solution of configuration 3%
Take by weighing chitosan 1.5g and be scattered in the 47mL sterile purified water, add 3mL36% acetic acid again, stir, leave standstill and treat the bubble cancellation, get the CS solution A of 3% (W/V).
(2) chitosan coats 3, the preparation of 5-dihydroxy-4-isopropyl toluylene sustained-release micro-spheres
Getting 2mL goes up in the step gained solution A adding small beaker; Get 0.5g crude drug 3,5-dihydroxy-4-isopropyl toluylene (benzene alkene is moral not) joins in the small beaker after as dissolution with solvents with a spot of ethanol, stir, mixed liquid B; Again B is added 15mL and contain in the disperse medium soybean oil of 5% (W/V) Span-80 (a kind of sorbitan monostearate class emulsifying agent, Span-80), stir, get mixture C; Add the glutaraldehyde (containing glutaraldehyde 3g) of 2.7mL50% among the C, solidify 6h; Centrifuge separates, and microsphere cleans with petroleum ether, and sucking filtration is drying to obtain product, envelop rate 36%, particle diameter 5.1 μ m.
The specific operation process of embodiment 2-5 only is with the difference of embodiment: related parameter is different, the kind difference of additive, and real data is with reference to shown in the last table.
Actual fabrication method of the present invention is not limited to above listed embodiment, all can change in claim institute restricted portion as the kind of relevant parameters, additive and consumption etc., and the actual product cut size that records is 0.1--100 μ m.
Claims (7)
1, a kind of chitosan coats 3, the sustained-release micro-spheres of 5-dihydroxy-4-isopropyl toluylene is characterized in that: described microsphere is a nucleocapsid structure, and its center is Powdered 3,5-dihydroxy-4-isopropyl toluylene layer, shell are the crosslinked condensation substance layer of chitosan and glutaraldehyde.
2, chitosan according to claim 1 coats 3, and the sustained-release micro-spheres of 5-dihydroxy-4-isopropyl toluylene is characterized in that: described microsphere is for spherical.
3, coat 3 according to each described chitosan in the claim 1-2, the sustained-release micro-spheres of 5-dihydroxy-4-isopropyl toluylene is characterized in that: described microspherulite diameter is the 0.1-100 micron.
4, a kind of preparation coats 3 as each described chitosan in the claim 1-3, the method of the sustained-release micro-spheres of 5-dihydroxy-4-isopropyl toluylene, it is characterized in that making described sustained-release micro-spheres raw materials of effective components and comprise following parts by weight composition: 10-30 parts of chitosans
3,1-9 parts of 5-dihydroxy-4-isopropyl toluylene,
10-50 parts of glutaraldehydes;
Its preparation method carries out according to following sequence of steps:
(1) configuration chitosan solution
Take by weighing chitosan and disperse to add acetic acid solution again in the sterilization deionized water, stir, leave standstill and treat the bubble cancellation, make w/v and be 2～5% configuration chitosan solution;
(2) coat the preparation sustained-release micro-spheres
The thing 3 of getting it filled, 5-dihydroxy-4-isopropyl toluylene with the alcohols solvent dissolving, joins then and goes on foot in the made chitosan solution solution, stirs; Again it is joined in the disperse medium that contains emulsifying agent, stir; Glutaraldehyde solution adds wherein, behind curing 4h～8h, and centrifugalize, petroleum ether cleans, sucking filtration, drying promptly gets the product chitosan and coats 3, the sustained-release micro-spheres of 5-dihydroxy-4-isopropyl toluylene.
5, preparation chitosan according to claim 4 coats 3, and the method for the sustained-release micro-spheres of 5-dihydroxy-4-isopropyl toluylene is characterized in that: described emulsifying agent is a kind of among sorbitan monostearate Span-80, Span-85 or the twen-80.
6, preparation chitosan according to claim 4 coats 3, and the method for the sustained-release micro-spheres of 5-dihydroxy-4-isopropyl toluylene 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.
7, preparation chitosan according to claim 4 coats 3, and the method for the sustained-release micro-spheres of 5-dihydroxy-4-isopropyl toluylene is characterized in that: described alcohols solvent is a kind of in methanol, ethanol, n-butyl alcohol or the isopropyl alcohol.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102240268A (en) * | 2011-05-06 | 2011-11-16 | 河北科技大学 | Sustained/controlled release microsphere of biological extract Genipin cross-linked chitosan coated stilbene compound and preparation method thereof |
| CN102302458A (en) * | 2011-09-15 | 2012-01-04 | 中国人民解放军军事医学科学院卫生装备研究所 | Long-acting sustained-release wound dressing containing levofloxacin sustained-release microspheres, and preparation method thereof |
| CN102657602A (en) * | 2012-05-22 | 2012-09-12 | 河北科技大学 | 3,5-dyhydroxyl-4-isopropyl diphenylethene chitosan gel and preparation method thereof |
| CN106902099A (en) * | 2016-02-16 | 2017-06-30 | 周幼文 | The isopropyl toluylene of 3,5 dihydroxy 4 (DHIS) is used as acaricide and its therapeutic application |
| CN112841773A (en) * | 2021-03-04 | 2021-05-28 | 杭州半边月文化创意有限公司 | Preparation process of tea breathing mask |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2334635T3 (en) * | 1999-12-06 | 2010-03-15 | Welichem Biotech Inc. | POLYHYDROXIESTILBEN AND STILBENE OXIDES AS ANTIPSORIASIC AGENTS AND INHIBITORS OF PROTEIN KINASE. |
| CN1130197C (en) * | 2001-11-15 | 2003-12-10 | 中国人民解放军第二军医大学 | Implanted slow-releasing antiseptic preparation and its preparing method |
| CN101341885A (en) * | 2008-08-29 | 2009-01-14 | 中国农业科学院植物保护研究所 | Preparation and uses of plant activation protein controllable sustained-release nano-microsphere |
| CN201404486Y (en) * | 2009-05-06 | 2010-02-17 | 河北科技大学 | Controlled-release micro sphere of chitosan coating 3,5-dyhydroxy-4-isopropyl toluylene |
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2009
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102240268A (en) * | 2011-05-06 | 2011-11-16 | 河北科技大学 | Sustained/controlled release microsphere of biological extract Genipin cross-linked chitosan coated stilbene compound and preparation method thereof |
| CN102240268B (en) * | 2011-05-06 | 2013-04-10 | 河北科技大学 | Sustained/controlled release microsphere of biological extract Genipin cross-linked chitosan coated stilbene compound and preparation method thereof |
| CN102302458A (en) * | 2011-09-15 | 2012-01-04 | 中国人民解放军军事医学科学院卫生装备研究所 | Long-acting sustained-release wound dressing containing levofloxacin sustained-release microspheres, and preparation method thereof |
| CN102657602A (en) * | 2012-05-22 | 2012-09-12 | 河北科技大学 | 3,5-dyhydroxyl-4-isopropyl diphenylethene chitosan gel and preparation method thereof |
| CN102657602B (en) * | 2012-05-22 | 2013-08-07 | 河北科技大学 | 3,5-dyhydroxyl-4-isopropyl diphenylethene chitosan gel and preparation method thereof |
| CN106902099A (en) * | 2016-02-16 | 2017-06-30 | 周幼文 | The isopropyl toluylene of 3,5 dihydroxy 4 (DHIS) is used as acaricide and its therapeutic application |
| CN112841773A (en) * | 2021-03-04 | 2021-05-28 | 杭州半边月文化创意有限公司 | Preparation process of tea breathing mask |
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