CN101628019B - Seabuckthorn oil-polylactide-coglycolide copolymer microspheres and preparation method thereof - Google Patents
Seabuckthorn oil-polylactide-coglycolide copolymer microspheres and preparation method thereof Download PDFInfo
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- CN101628019B CN101628019B CN2009100658176A CN200910065817A CN101628019B CN 101628019 B CN101628019 B CN 101628019B CN 2009100658176 A CN2009100658176 A CN 2009100658176A CN 200910065817 A CN200910065817 A CN 200910065817A CN 101628019 B CN101628019 B CN 101628019B
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Abstract
The invention relates to seabuckthorn oil-polylactide-coglycolide copolymer microspheres and a preparation method thereof; the coated effective component in microspheres is seabuckthorn oil and the matrix component of wrappage is polylactide-coglycolide copolymer (PLGA). Polyving alcohol (PVA) is used as modifier, and the slow release PLGA microspheres can be prepared by the W/O/W double emulsion method (aka solvent evaporation method, solvent solidification method or solvent extraction method) under the action of mechanical agitation. Smooth microspheres surface, round and normal spheres, uniform particle size and good embedding can be observed under a microscope.
Description
Technical field
The present invention relates to a kind of sustained-release micro-spheres of health substance Oleum Hippophae, relate to a kind of Oleum Hippophae-polylactic acid-glycolic guanidine-acetic acid copolymer microsphere and preparation method thereof specifically.
Background technology
Fructus Hippophae (Hippophae ham noides L inn) belongs to the Elaeangnaceae hippophae plant, claims the vinegar willow again, is Ancient Times in China Tibetan medicine, Mongolian medicine's common drug, formally lists Chinese Pharmacopoeia in 1977 in.The Oleum Hippophae active component that from hippophae rhamnoides seed, extracts has 106 kinds more than, and unsaturated fatty acid is up to 68%, and content of vitamin E also contains compositions such as abundant vitamin K and carotenoid greater than 1mg/g.Medical research shows, Oleum Hippophae antiinflammatory granulation promoting has good action to the repairing of digestive system.Fructus Hippophae pyrite is to myocardial ischemia, hyperlipidemia, and the coronary atherosclerosis curative effect is excellent, and can also kill cancer cell, contains the superoxide dismutase (SOD) of abundant removing free radical effect, is important defying age material.The special proportioning of bioactive substance in the Oleum Hippophae in Oleum Hippophae, coordinate and strengthened its opposing and the treatment disease effect.Through clinical verification; Oleum Hippophae has the effect of strengthening the body resistance, strengthening the spleen and nourishing the stomach, activating blood circulation to dissipate blood stasis, vessel softening, fat-reducing liver-protecting, human body immunity improving power and treatment and the multiple disease of prevention; Especially cancer is had the effect of treatment and auxiliary treatment, uncomfortable disease, digestive tract disease and burn, scald that radiation and chemotherapy is caused all have certain curative effect.
Although Oleum Hippophae has good health care effect like this, because it contains a large amount of unsaturated fatty acids and other readily oxidizable substances, so the Oleum Hippophae product all faces an easy problem of oxidation.Greasy antioxidation during generally except traditional storage shading airtight, be mostly to add antioxidant to prolong the oil and fat product shelf life.Except traditional BHT, TBHQ etc. the synthetic antioxidant, open saddle spirit etc. and also study for Fructus Hippophae and the anti-oxidation efficacy of ginkgetin in Oleum Hippophae.And the employing microencapsulation technology is processed the Oleum Hippophae capsule powders with purified Oleum Hippophae, is to prolong the shelf life of Oleum Hippophae and Related product thereof and the focus of shelf-life at present; Also can reach the suitability for industrialized production purpose through this technology; The Oleum Hippophae microcapsule product is come into the market, and this is the exploitation of Oleum Hippophae health food for preventing the Oleum Hippophae oxidation deterioration; Even the exploitation of health care medicine provides cheap and good-quality Oleum Hippophae powder, all has big practical value.At present there have been some researchs, Ge Hanying, Nie Bin scruple not to prepare the Oleum Hippophae microcapsule and studied, and made the relative better products of embedding rate for gelatin, arabic gum about the Oleum Hippophae microencapsulation.A kind of novel wall material for preparing microsphere at present; Polylactic acid-glycolic guanidine-acetic acid copolymer (PLGA); Since its in vivo the metabolism end product be water and carbon dioxide; Intermediate product lactic acid is intravital normal carbohydrate metabolism product, has avirulence, non-irritating advantage and in the field of medicaments extensive use, prominent the releasing obviously of the medicine microcapsule of producing slowed down.Consider to be applied to the preparation of Oleum Hippophae microcapsule, may obtain higher embedding rate; Because the PLGA surface can be brought in constant renewal in, its surface constantly degraded forms micropore, slowly exposes the Oleum Hippophae of inner packet envelope, thereby obtains slow release effect preferably, better brings into play health-care effect again.But through consulting document, the present domestic report that does not still have Oleum Hippophae PLGA microsphere and Related Experimental Study thereof.
Summary of the invention
The object of the invention is that host material prepares Oleum Hippophae-polylactic acid-glycolic guanidine-acetic acid copolymer microsphere and preparation method thereof with PLGA in order to provide a kind of just.This method for preparing is W/O/W emulsion seasoning (having another name called solvent evaporation method, solvent solidification method and solvent extraction method), uses macromolecular material PLGA to seal Oleum Hippophae as carrier material, under the effect of magnetic agitation, prepares slow release Oleum Hippophae microsphere.The microsphere that adopts this method to prepare has the smooth surface rounding, regular particles does not have adhesion, the good characteristics of embedding.
The object of the invention can be realized through following technique measures:
Oleum Hippophae of the present invention-polylactic acid-glycolic guanidine-acetic acid copolymer microsphere comprises being wrapped and is encapsulated in Oleum Hippophae in the wrappage and the wrappage that is prepared from as matrix components polylactic acid-glycolic guanidine-acetic acid copolymer.
The method for preparing of Oleum Hippophae of the present invention-polylactic acid-glycolic guanidine-acetic acid copolymer microsphere may further comprise the steps:
The preparation of a, organic facies: get dichloromethane and ethyl acetate at 25～100: 0～75 by volume, preparation 4ml mixed liquor,
B, polylactic acid-glycolic guanidine-acetic acid copolymer (Polylactide-coglycolide, taking by weighing and dissolve PLGA): take by weighing polylactic acid-glycolic guanidine-acetic acid copolymer 1 20mg～170mg, add in the prepared organic facies of a step, and make it dissolving;
The adding of c, Oleum Hippophae: get Oleum Hippophae 190 μ l～210 μ l, join in the prepared good organic phase solution of b step, in advance about emulsifying supersound process 1min;
The preparation of d, water: get the polyvinyl alcohol as dressing agent (PVA) that is the smalls shape after 2.2g～3.8g pulverizes, join in the 25ml distilled water, the water bath with thermostatic control heating is thoroughly dissolved polyvinyl alcohol under 45 ℃～55 ℃ condition;
E, emulsifying and microsphere preparation: the organic facies that the c step is prepared is poured the prepared aqueous phase of d step into, carries out ultrasonic emulsification and handles, and gets O/W emulsion; Carry out normal pressure magnetic agitation volatilization organic solvent, carry out centrifugal treating with centrifuge subsequently, afterwards with the precipitate that obtains with deionized water centrifuge washing 5 times, the about 2d of lyophilization obtains product, conventional lyophilizing preservation.
In the guanidine-acetic acid of polylactic acid-glycolic described in the present invention copolymer (PLGA), the mass percent of polylactic acid (PLA) and hydroxyacetic acid (PGA) is 75%: 25%, and its molecular weight is about 2.0 * 10
4
Degree of hydrolysis as the polyvinyl alcohol (PVA) of dressing agent among the present invention is 87～90%, and the polymeric chain joint number is 1700～1750, and weight average molecular weight is 1.0～2.0 * 10
4, solution concentration is 0～12.5%.
The emulsifying ultrasonic time is 10-30min in the ultrasonic emulsification treatment process described in the e step of the present invention, and the emulsifying ultrasonic power is 120-240W, and at room temperature carries out; The magnetic agitation time is about 3-5h, and mixing speed is 600-1500RPM; Centrifuge speed is 3500r/min, and centrifugation time is about 5min.
Beneficial effect of the present invention is following:
Because the present invention adopts suitable PLA: the PLGA of PGA mass ratio is wrappage host material (Biodegradable material); Not only improved the embedding effect of Oleum Hippophae; And can form the good microsphere of form, and can prevent that the Oleum Hippophae that is prone to oxidation from contacting with oxygen, plays good antioxidant effect; The effect of slow release be can play again, Oleum Hippophae concentration that the administration part keeps relative stability and the utilization ratio that improves Oleum Hippophae made.
Description of drawings
The following 100 times of bust shot figure of Fig. 1 Oleum Hippophae-PLGA biological microscope
The following 400 times of bust shot figure of Fig. 2 Oleum Hippophae-PLGA biological microscope
The specific embodiment
To combine embodiment to make further detailed description below the present invention:
In the guanidine-acetic acid of polylactic acid-glycolic described in following examples copolymer (PLGA), the mass percent of polylactic acid (PLA) and hydroxyacetic acid (PGA) is 75%: 25%, and its molecular weight is about 2.0 * 10
4Degree of hydrolysis as the polyvinyl alcohol (PVA) of dressing agent is 87～90%, and the polymeric chain joint number is 1700～1750, and weight average molecular weight is 1.0～2.0 * 10
4, solution concentration is 0～12.5%.
Embodiment 1:
(1) preparation of organic facies: pipette the dichloromethane of 4ml with pipet, join in the small beaker.
(2) the taking by weighing and dissolve of PLGA: on the precise electronic balance, take by weighing 125mgPLGA, add in the organic facies of preparation, make the PLGA dissolving.
(3) adding of Oleum Hippophae: pipette the Oleum Hippophae of 200 μ l with liquid-transfering gun, join in the organic facies for preparing supersound process 1min.
(4) preparation of water: take by weighing the PVA that is the smalls shape after 2.5g pulverizes at electronic balance, in the 150ml beaker, add the 25ml distilled water, PVA is poured into, 50 ℃ of water bath with thermostatic control heating beakers thoroughly dissolve PVA.
(5) emulsifying and microsphere preparation: pour the organic facies after ultrasonic into PVA dissolved aqueous phase, carry out the ultrasonic emulsification processing of 10min, get O/W emulsion with the power of 150W.Rotating speed with 600RPM carries out normal pressure magnetic agitation volatilization organic solvent subsequently, uses centrifuge with the centrifugal 5min of 3500r/min speed subsequently, will obtain the precipitate with deionized water centrifuge washing 5 times, and the about 2d of lyophilization obtains product.
Embodiment 2:
(1) preparation of organic facies: pipette the ethyl acetate of dichloromethane and the 3ml of 1ml respectively with pipet, preparation 4ml mixed liquor joins in the small beaker.
(2) the taking by weighing and dissolve of PLGA: on the precise electronic balance, take by weighing 135mgPLGA, add in the organic facies of preparation, make the PLGA dissolving.
(3) adding of Oleum Hippophae: pipette the Oleum Hippophae of 200 μ l with liquid-transfering gun, join in the organic facies for preparing supersound process 1min.
(4) preparation of water: take by weighing the PVA that is the smalls shape after 2.8g pulverizes at electronic balance, in the 150ml beaker, add the 25ml distilled water, PVA is poured into, 50 ℃ of water bath with thermostatic control heating beakers thoroughly dissolve PVA.
(5) emulsifying and microsphere preparation: pour the organic facies after ultrasonic into PVA dissolved aqueous phase, carry out the ultrasonic emulsification processing of 11min, get O/W emulsion with the power of 160W.Rotating speed with 600RPM carries out normal pressure magnetic agitation volatilization organic solvent subsequently, uses centrifuge with the centrifugal 5min of 3500r/min speed subsequently, will obtain the precipitate with deionized water centrifuge washing 5 times, and the about 2d of lyophilization obtains product.
Embodiment 3:
(1) preparation of organic facies: pipette the ethyl acetate of dichloromethane and the 2.5ml of 1.5ml respectively with pipet, preparation 4ml mixed liquor joins in the small beaker.
(2) the taking by weighing and dissolve of PLGA: on the precise electronic balance, take by weighing 145mgPLGA, add in the organic facies of preparation, make the PLGA dissolving.
(3) adding of Oleum Hippophae: pipette the Oleum Hippophae of 200 μ l with liquid-transfering gun, join in the organic facies for preparing supersound process 1min.
(4) preparation of water: take by weighing the PVA that is the smalls shape after 3.0g pulverizes at electronic balance, in the 150ml beaker, add the 25ml distilled water, PVA is poured into, 50 ℃ of water bath with thermostatic control heating beakers thoroughly dissolve PVA.
(5) emulsifying and microsphere preparation: pour the organic facies after ultrasonic into PVA dissolved aqueous phase, carry out the ultrasonic emulsification processing of 12min, get O/W emulsion with the power of 170W.Rotating speed with 600RPM carries out normal pressure magnetic agitation volatilization organic solvent subsequently, uses centrifuge with the centrifugal 5min of 3500r/min speed subsequently, will obtain the precipitate with deionized water centrifuge washing 5 times, and the about 2d of lyophilization obtains product.
Embodiment 4:
(1) preparation of organic facies: pipette dichloromethane and the ethyl acetate of each 2ml respectively with pipet, preparation 4ml mixed liquor joins in the small beaker.
(2) the taking by weighing and dissolve of PLGA: on the precise electronic balance, take by weighing 155mgPLGA, add in the organic facies of preparation, make the PLGA dissolving.
(3) adding of Oleum Hippophae: pipette the Oleum Hippophae of 200 μ l with liquid-transfering gun, join in the organic facies for preparing supersound process 1min.
(4) preparation of water: take by weighing the PVA that is the smalls shape after 3.2g pulverizes at electronic balance, in the 150ml beaker, add the 25ml distilled water, PVA is poured into, 50 ℃ of water bath with thermostatic control heating beakers thoroughly dissolve PVA.
(5) emulsifying and microsphere preparation: pour the organic facies after ultrasonic into PVA dissolved aqueous phase, carry out the ultrasonic emulsification processing of 10min, get O/W emulsion with the power of 180W.Rotating speed with 600RPM carries out normal pressure magnetic agitation volatilization organic solvent subsequently, uses centrifuge with the centrifugal 5min of 3500r/min speed subsequently, will obtain the precipitate with deionized water centrifuge washing 5 times, and the about 2d of lyophilization obtains product.
Embodiment 5:
(1) preparation of organic facies: pipette the ethyl acetate of dichloromethane and the 1ml of each 3ml respectively with pipet, preparation 4ml mixed liquor joins in the small beaker.
(2) the taking by weighing and dissolve of PLGA: on the precise electronic balance, take by weighing 165mgPLGA, add in the organic facies of preparation, make the PLGA dissolving.
(3) adding of Oleum Hippophae: pipette the Oleum Hippophae of 200 μ l with liquid-transfering gun, join in the organic facies for preparing supersound process 1min.
(4) preparation of water: take by weighing the PVA that is the smalls shape after 3.5g pulverizes at electronic balance, in the 150ml beaker, add the 25ml distilled water, PVA is poured into, 50 ℃ of water bath with thermostatic control heating beakers thoroughly dissolve PVA.
(5) emulsifying and microsphere preparation: pour the organic facies after ultrasonic into PVA dissolved aqueous phase, carry out the ultrasonic emulsification processing of 11min, get O/W emulsion with the power of 190W.Rotating speed with 600RPM carries out normal pressure magnetic agitation volatilization organic solvent subsequently, uses centrifuge with the centrifugal 5min of 3500r/min speed subsequently, will obtain the precipitate with deionized water centrifuge washing 5 times, and the about 2d of lyophilization obtains product.
Adopt microspheres prepared smooth surface rounding of the present invention, regular particles does not have adhesion (Fig. 1), shows its embedding good (Fig. 2) through amplifying observation.
Claims (4)
1. Oleum Hippophae-polylactic acid-glycolic guanidine-acetic acid copolymer microsphere is characterized in that: said microsphere comprises being wrapped and is encapsulated in Oleum Hippophae in the wrappage and the wrappage that is prepared from as matrix components polylactic acid-glycolic guanidine-acetic acid copolymer; Its preparation method may further comprise the steps:
The preparation of a, organic facies: get dichloromethane and ethyl acetate at 25～100: 0～75 by volume, preparation 4ml;
The taking by weighing and dissolve of b, polylactic acid-glycolic guanidine-acetic acid copolymer: get polylactic acid-glycolic guanidine-acetic acid copolymer 1 20mg～170mg, add in the prepared organic facies of a step, and make it dissolving;
The adding of c, Oleum Hippophae: get Oleum Hippophae 190 μ l～210 μ l, join in the prepared good organic phase solution of b step, in advance emulsifying supersound process 1min;
The preparation of d, water: get the polyvinyl alcohol as dressing agent that is the smalls shape after 2.2g～3.8g pulverizes, join in the 25ml distilled water, the water bath with thermostatic control heating is thoroughly dissolved polyvinyl alcohol under 45 ℃～55 ℃ condition;
E, emulsifying and microsphere preparation: the organic facies that the c step is prepared is poured the prepared aqueous phase of d step into, carries out ultrasonic emulsification and handles, and gets O/W emulsion; Carry out normal pressure magnetic agitation volatilization organic solvent, carry out centrifugal treating with centrifuge subsequently, afterwards with the precipitate that obtains with deionized water centrifuge washing 5 times, lyophilization 2d obtains product.
2. Oleum Hippophae according to claim 1-polylactic acid-glycolic guanidine-acetic acid copolymer microsphere is characterized in that: in the said polylactic acid-glycolic guanidine-acetic acid copolymer, the mass percent of polylactic acid and hydroxyacetic acid is 75%:25%, and its molecular weight is about 2.0 * 10
4
3. Oleum Hippophae according to claim 1-polylactic acid-glycolic guanidine-acetic acid copolymer microsphere is characterized in that: the degree of hydrolysis as the polyvinyl alcohol of dressing agent is 87～90%, and the polymeric chain joint number is 1700～1750, and weight average molecular weight is 1.0～2.0 * 10
4
4. Oleum Hippophae according to claim 1-polylactic acid-glycolic guanidine-acetic acid copolymer microsphere is characterized in that: the emulsifying ultrasonic time is 10-30min in the ultrasonic emulsification treatment process described in the e step, and the emulsifying ultrasonic power is 120-240W, and at room temperature carries out; The magnetic agitation time is 3-5h, and mixing speed is 600-1500RPM; Centrifuge speed is 3500r/min, and centrifugation time is at 5min.
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| CN106190768A (en) * | 2016-07-22 | 2016-12-07 | 重庆修贤生物科技有限公司 | Oligofructose and oligochitosan application in vinegar goods |
| CN107510057A (en) * | 2017-10-09 | 2017-12-26 | 无锡盛雅生物科技有限公司佛山分公司 | A kind of preparation method of mackerel fish oil and fat-soluble tea polyphenol complex microsphere |
| CN112168850B (en) * | 2020-10-10 | 2022-05-24 | 青海大学 | Preparation method of hydrophilic seabuckthorn sterol |
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| CN1857728A (en) * | 2006-03-14 | 2006-11-08 | 中国人民解放军第二军医大学 | Nanometer magnetic polylactic acid-phenyl arsine glycollate microballoon and its use |
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| CN1857728A (en) * | 2006-03-14 | 2006-11-08 | 中国人民解放军第二军医大学 | Nanometer magnetic polylactic acid-phenyl arsine glycollate microballoon and its use |
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| Title |
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| 陈国广等.聚乳酸羟基乙酸载药微球的研究进展.《华西药学杂志》.2006,第21卷(第2期),181-183. * |
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