CN101618021B - Chitosan coating medicine slow release microsphere and preparation method thereof - Google Patents
Chitosan coating medicine slow release microsphere and preparation method thereof Download PDFInfo
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- CN101618021B CN101618021B CN2009100751283A CN200910075128A CN101618021B CN 101618021 B CN101618021 B CN 101618021B CN 2009100751283 A CN2009100751283 A CN 2009100751283A CN 200910075128 A CN200910075128 A CN 200910075128A CN 101618021 B CN101618021 B CN 101618021B
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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
Technical field
The present invention relates to a kind of pharmaceutical preparation and preparation method thereof, specifically a kind of chitosan coating medicine slow release microsphere and preparation method thereof.
Background technology
Resveratrol (3 as medicine, 4 ', 5-trihydroxy stilbene), oxidized resveratrol (2,4,3 ', 5 '-tetrahydroxystilbene), Lignum pterocarpi indici Stilbene (3, the 5-dimethoxy-4 ' '-hydroxy stibene), Rhizoma Euonymus China fir alcohol (3,4,3 ', 5 '-tetrahydroxystilbene), belong to active non-flavone polyphenol substance, extensively be present in natural food or the plant, they have significant antiinflammatory in a large amount of studies show that, antioxidation, antibiotic, free radical resisting and anticoagulant, antithrombotic, the effect of lipidemia can be used for arteriosclerosis, coronary heart disease, viral hepatitis, acquired immune deficiency syndrome (AIDS), the prevention of diseases such as cancer and treatment.
Because resveratrol, oxidized resveratrol, the Lignum pterocarpi indici Stilbene contains the phenolic hydroxyl group of different numbers respectively in the Rhizoma Euonymus China fir alcohol molecule, easily oxidized in air, causes the color of product and performance to change; And the existence of phenolic hydroxyl group also makes above-mentioned several chemical compound be subject to the influence of pH, may produce complicated variation as medicine or health product and other chemical compounds when composite, influences itself and brings into play curative effect effectively.
(chitosan is that it is good that it has excellent biological compatibility by the poly-aminopolysaccharide of a kind of natural polymer that obtains behind the chitin deacetylase base CS) to chitosan; Can be absorbed fully by organism in vivo by the plurality of enzymes biodegradation; Increase medicine to biomembranous permeability, help medicine and in cell, bring into play drug effect.As a kind of good biological organic carrier, free amine group is arranged on 2 of the molecule of chitosan own, can make it to form key bridge solidified microsphere by the aldehyde ammonia condensation reaction, also can utilize this character to be applied to the research of slow releasing preparation.Sustained-release micro-spheres is a kind of novel form in the medicine, and its ultimate principle is to utilize technique for packing that pharmaceutical pack is overlayed on the small cryptomere preparation of formation in the capsule material, increases stability of drug, is convenient to take, and reaches the purpose of slow controlled release simultaneously.
Summary of the invention
The technical problem to be solved in the present invention provides a kind of chitosan coating medicine slow release microsphere, and softgel shell is a chitosan, coats the core medicine and be a kind of in resveratrol, oxidized resveratrol, Lignum pterocarpi indici Stilbene or the Rhizoma Euonymus China fir alcohol.This sustained-release micro-spheres structure has increased the stability of core medicine, can realize the purpose of slow controlled release.Chitosan itself also 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 preparation cost is low, and envelop rate is 10--50%.
The present invention will solve above-mentioned technical problem, is to be achieved by following technical scheme:
A kind of chitosan coating medicine slow release microsphere comprises softgel shell, is coated on the core medicine in the softgel shell, and 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.
Microspherulite diameter is the 2-100 micron.
Described microsphere is the sphere of rounding.
Have hole on the described microsphere shell wall.
The present invention also provides the preparation method of above-mentioned chitosan coating medicine slow release microsphere, it 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.
Described preparation method is carried 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 5h-10h, centrifugalize, petroleum ether cleans, sucking filtration, drying gets product, i.e. chitosan coating medicine slow release microsphere.
Described emulsifying agent is a kind of among sorbitan monostearate Span-80 (Span-80), Span-85 (this dish-85), the twen-80 (tween 80), also can be the mixture of Span-80 (Span-80) and 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 co-emulsifier is a kind of in methanol, ethanol, n-butyl alcohol or the isopropyl alcohol.
In the technique scheme, the purpose of adding emulsifying agent is to make medicine and disperse medium form the system of water-in-oil type, thereby forms the minimicrosphere that is coated with medicine; The purpose of adding disperse medium is to make it serve as oil phase; Add disperse medium, effect on the one hand is to make medicine dissolution, fully mix with system, and be that assosting effect is played in the formation of microsphere on the other hand.
Technique scheme of the present invention is to utilize the natural macromolecule amylose chitosan, coats core medicine resveratrol, oxidized resveratrol, Lignum pterocarpi indici Stilbene or Rhizoma Euonymus China fir alcohol, forms microsphere rounding, good dispersion.Because the advantage that had of chitosan itself, make the microsphere dosage form medicine not only the stability of former medicine be improved, and realized the purpose of medicine sustained and controlled release; Also make things convenient for and the other drug compatibility in addition.This sustained-release micro-spheres preparation method is simple, and preparation cost is low, and the envelop rate of preparing microsphere is 10-50%, and used cross-linking agent glutaraldehyde is the saturated toluene solution of glutaraldehyde, can make that the microsphere surface of preparation is more smooth.This preparation method is suitable for the slow release formulation of making medicine resveratrol, oxidized resveratrol, Lignum pterocarpi indici Stilbene and Rhizoma Euonymus China fir alcohol.
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 overall structure sketch map of sustained-release micro-spheres of the present invention;
Fig. 2 is the vertical profile profile of Fig. 1.
Among the figure: 1, powdered form core medicine-resveratrol, oxidized resveratrol, Lignum pterocarpi indici Stilbene or Rhizoma Euonymus China fir alcohol;
The condensation layer of 2, shell--chitosan and glutaraldehyde;
3, hole; 4, gauffer.
The specific embodiment
Embodiment 1-6 is respectively chitosan and coats sustained-release micro-spheres of different pharmaceutical and preparation method thereof
The structure of each sustained-release micro-spheres comprises spherical softgel shell 2, is coated on the Powdered core medicine in the softgel shell 2 as shown in Figure 1 and Figure 2.Described softgel shell is the condensation substance of chitosan and glutaraldehyde, and core medicine composition is respectively resveratrol, oxidized resveratrol, Lignum pterocarpi indici Stilbene, Rhizoma Euonymus China fir alcohol, resveratrol, oxidized resveratrol.
Microsphere is the sphere of the rounding of particle diameter 2-100 micron, and is rough, has gauffer 4, has hole 3 on the shell wall.
Among the embodiment 1-embodiment 6, it is as shown in the table to make sustained-release micro-spheres raw materials of effective components proportioning.The preparation method of 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, making w/v is the configuration chitosan solution A of 1-5%;
(2) coat the preparation sustained-release micro-spheres
Get it filled thing resveratrol, oxidized resveratrol, Lignum pterocarpi indici Stilbene or Rhizoma Euonymus China fir alcohol with the dissolving of alcohols co-emulsifier, join in the made A solution of step then, stir, must mixed liquid B; B is joined in the disperse medium that contains emulsifying agent, stir, get mixed liquor C; Other gets among the saturated toluene solution adding C of glutaraldehyde, behind curing 5h～10h, and centrifugalize, petroleum ether cleans, sucking filtration, drying, getting product is the sustained-release micro-spheres that chitosan coats resveratrol, oxidized resveratrol, Lignum pterocarpi indici Stilbene or Rhizoma Euonymus China fir alcohol.
For example the preparation method of sustained-release micro-spheres is carried out according to the following steps order among the embodiment 1:
(1) chitosan (CS) solution of configuration 3%
Take by weighing chitosan 1.5g and be scattered in the 47mL sterile purified water, add 36% acetic acid 3mL again, stir, leave standstill and treat the bubble cancellation, get the CS solution A of 3% (W/V).
(2) chitosan coats the preparation of resveratrol (3,4 ', 5-trihydroxy stilbene) sustained-release micro-spheres
Getting 2mL goes up in the step gained solution A adding small beaker; Get 0.5g crude drug resveratrol (3,4 ', 5-trihydroxy stilbene) respectively, join in the small beaker, stir, must mix ripple B with a spot of ethanol (as co-emulsifier) dissolving; Again B is added 15mL and contain in the soybean oil (as disperse medium) of 5% (W/V) Span-80 (a kind of sorbitan monostearate class emulsifying agent, Span-80), stir, get mixture C; Add the saturated toluene solution (contain glutaraldehyde and be about 1g) of glutaraldehyde of 1mL50% among the C, solidify 6h; Centrifuge separates, and microsphere cleans with petroleum ether, and sucking filtration is drying to obtain product, envelop rate 50%, particle diameter 6.3 μ m.
Claims (5)
1. the preparation method of a chitosan coating medicine slow release microsphere, wherein: described sustained-release micro-spheres comprises softgel shell, is coated on the medicine in the softgel shell, described softgel shell is the condensation substance of chitosan and glutaraldehyde, and the core medicine is a kind of in resveratrol, oxidized resveratrol, Lignum pterocarpi indici Stilbene or the Rhizoma Euonymus China fir alcohol; Described sustained-release micro-spheres is the sphere of rounding, and its particle diameter is the 2-100 micron, has hole on the microsphere shell wall, makes described 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.
2. the preparation method of chitosan coating medicine slow release microsphere according to claim 1 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 coating medicine slow release microsphere.
3. the preparation method of chitosan coating medicine slow release microsphere according to claim 2 is characterized in that: described emulsifying agent is a kind of among Span-80, Span-85, the twen-80, or is the mixture of Span-80 and twen-80.
4. the preparation method of chitosan coating medicine slow release microsphere according to claim 2 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.
5. the preparation method of chitosan coating medicine slow release microsphere according to claim 2 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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Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102219652B (en) * | 2011-05-05 | 2013-04-10 | 三明华健生物工程有限公司 | Method for preparing water-soluble resveratrol from giant knotweed rhizome |
| 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 |
| CN102579364B (en) * | 2012-03-05 | 2013-10-09 | 河北科技大学 | Sustained or controlled release microsphere of valnemulin/valnemulin salts and preparation method thereof |
| CN103417556A (en) * | 2012-05-17 | 2013-12-04 | 昆明制药集团股份有限公司 | Applications of stilbene compounds |
| CN104257640B (en) * | 2014-09-28 | 2016-06-01 | 郝磊 | A kind of Pterostilene composition and its preparation method |
| CN104689771B (en) * | 2015-03-05 | 2017-03-01 | 华南农业大学 | A kind of preparation method of oxidized resveratrol microcapsule and products thereof |
| CN111763141A (en) * | 2020-07-07 | 2020-10-13 | 昆明翔昊科技有限公司 | Method for extracting piceatannol from rhubarb medicinal materials, microcapsule molecule embedding method and application of microcapsule molecule embedding method in food and health care products |
| CN111704530A (en) * | 2020-07-07 | 2020-09-25 | 昆明翔昊科技有限公司 | Method for extracting piceatannol from rheum officinale, microcapsule molecule embedding method and application of piceatannol in cosmetics |
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| US6228291B1 (en) * | 1998-12-17 | 2001-05-08 | Korea Research Institute Of Chemical Company | Process for preparing controlled-released chitosan microcapsule |
| WO2003013552A1 (en) * | 2001-08-04 | 2003-02-20 | Sang-Mun Han | Embolic materials comprising of chitin and/or chitosan and method for preparing thereof |
| CN1951369A (en) * | 2006-11-03 | 2007-04-25 | 李万忠 | Coated nanoliposomes of resveratrol and preparation method thereof |
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Patent Citations (4)
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| US6228291B1 (en) * | 1998-12-17 | 2001-05-08 | Korea Research Institute Of Chemical Company | Process for preparing controlled-released chitosan microcapsule |
| WO2003013552A1 (en) * | 2001-08-04 | 2003-02-20 | Sang-Mun Han | Embolic materials comprising of chitin and/or chitosan and method for preparing thereof |
| CN1951369A (en) * | 2006-11-03 | 2007-04-25 | 李万忠 | Coated nanoliposomes of resveratrol and preparation method thereof |
| CN101249081A (en) * | 2008-02-15 | 2008-08-27 | 南京大渊美容保健有限公司 | Administer orally controlled release drug administration pharmaceutical tablet |
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