CN101773475B - Preparation method of capsicine micro spheres - Google Patents
Preparation method of capsicine micro spheres Download PDFInfo
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- CN101773475B CN101773475B CN2010100313597A CN201010031359A CN101773475B CN 101773475 B CN101773475 B CN 101773475B CN 2010100313597 A CN2010100313597 A CN 2010100313597A CN 201010031359 A CN201010031359 A CN 201010031359A CN 101773475 B CN101773475 B CN 101773475B
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Abstract
The invention discloses a preparation method of capsicine micro spheres, which comprises the following steps: (1) dissolving capsicine and carrier materials into an organic solvent to obtain an oil phase according to the mixing ratio of 100 to 250 mg/27 to 100 mg/2 to 5 mL; (2) dissolving emulsifying agents into water as a water phase, wherein the concentration of the emulsifying agents in the water phase is between 5 and 30 mg/mL; and (3) adding the oil phase into the water phase for forming oil-in-water latex emulsion according to the volume ratio of 1/20 to 1/40 under the conditions of the temperature between 20 and 30 DEG C and the stirring speed between 500 and 1200 rpm, continuously stirring the oil-in-water latex emulsion for volatilizing the organic solvent, carrying out centrifugation for collecting micro spheres, washing the micro spheres by distilled water, and preparing the capsicine micro spheres through freeze drying. The capsicine micro spheres prepared by the method of the invention can be made into various slow-release preparations, the stimulation of the capsicine can be reduced, and the medicine concentration can be maintained for a long time, so the medication times can be reduced, the toxic and side effect can be reduced, and the adaptability of patients can be improved.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, particularly relate to a kind of method for preparing of capsaicin alkali microsphere.
Background technology
Capsaicin (Capsaicin) is from natural capsicum, to extract a kind of Rhizoma et radix valerianae amide alkaloid that obtains; Its chemical structure names is: N-[(4-hydroxyl-3-methoxyl group-phenyl)-methyl]-8-methyl-(instead)-6-nonene amide can obtain through methods such as plant extract, biosynthesis, chemosynthesis and cell culture.Capsaicin has multiple complex physical pharmacological activity; Comprise antiinflammatory, analgesia, antibacterial, antipruritic, prevent and treat cardiovascular disease, promote lipid metabolism, effects such as mediation apoptosis of tumor cells; Wherein comparatively unique is its long-acting analgesic effect and novel analgesic mechanism: the mainly release through the peptide P material that affects the nerves, synthetic and preserved analgesia, itching-relieving action; Experimentation shows that the analgesic activity and the morphine of capsaicin are equal to; But more lasting than morphine, the former analgesia time is 7～10 days, and morphine then is 6h.The capsaicin purposes is very extensive, and the field of medicaments application potential is huge.Illness such as the main clinically serious refractory post-herpetic neuralgia of application of treatment of capsaicin, sciatica, diabetic neuralgia, serious symptom rheumatic arthritis and serious psoriasis; Evident in efficacy; As the topical pain relief medicine, be embodied on the American Pharmacopeia 24 editions.Oral medicine and injection by capsaicine crystals is processed can play strong analgesic activity, and more effective than ibuprofen, injection has powerful analgesic activity to the severe pain because of generations such as extensive wound, cancer of late stage, and do not have addiction property, can replace dolantin to use.
But the first pass effect of hepar that has height because of capsaicin; Half-life is too short, and oral administration biaavailability is also lower, and capsaicin adopts the topical dosage form mostly at present; Like cream, patch, ointment, membrane and cataplasma etc.; But skin irritation is in various degree all arranged,, limited its clinical practice like skin scorch pain sense, regional area hyperemia and neurogenic inflammatory reaction; The capsaicin that how to utilize novel medicine-feeding technology to develop multiple dosage form is avoided its first pass effect of hepar, prolongs biological half-life and reduces zest becomes new drug development for clinical use important directions.
The microsphere technology at first realizes long lasting purpose through the rate of release of regulating and control medicine as a kind of novel medicine-feeding technology, can protect medicine again simultaneously; Cover the poor taste of medicine; And reduce administration number of times and medicine irritation, and reduce toxicity and side effect, improve curative effect.Seeing that the problem that capsaicin exists in process of clinical application; The present invention intends and adopts macromolecular material parcel capsaicin to prepare the biological degradability sustained-release micro-spheres, avoids first pass effect of hepar, reduces zest; Keep drug level for a long time; To reduce administration number of times, reduce toxic and side effects, improve patient's compliance.
Summary of the invention
The purpose of this invention is to provide a kind of preparation method of capsicine micro spheres.This method adopts natural biological degradable high polymer material gelatin or synthesising biological degradable high polymer material polylactic acid (PLA) or polylactic-co-glycolic acid (PLGA) as carrier, prepares capsicine micro spheres through emulsion-solvent evaporation method.Microsphere form rounding, drug loading are 1～27%, and envelop rate is 6～85%, and mean diameter can be regulated and control between 2～28 μ m.This microsphere can be used as the carrier of new type analgesic capsaicin, through muscle, subcutaneous, joint cavity injection or heeling-in administration, reduces the zest of capsaicin, and the drug release rate of regulation and control capsaicin reduces administration number of times, improves patient's compliance.
Capsicine micro spheres preparation of the present invention comprises following method:
A kind of preparation method of capsicine micro spheres, its characteristic comprises the steps:
(1) in 100-250mg: the ratio of 27-100mg: 2-5mL is dissolved in capsaicin and carrier material and obtains oil phase in the organic solvent;
(2) with emulsifiers dissolve in water as water, said emulsifying agent is 5～30mg/mL in the concentration of aqueous phase;
(3) at 20 ℃～30 ℃, mixing speed is under the condition of 500～1200rpm, is 1: 20～1: 40 ratio by volume; Said oil phase is added said aqueous phase, form O/w emulsion, continue to stir the volatilization organic solvent; Centrifugal collection microsphere; Use distilled water wash, capsicine micro spheres is processed in lyophilization.
Preferred polylactic acid of carrier material or polylactic-co-glycolic acid.
The preferred dichloromethane of organic solvent, ethyl acetate or volume ratio are 1: 1.5～9 the acetone and the mixed solvent of dichloromethane.
The preferred gelatin of emulsifying agent, polyvinyl alcohol or mass ratio are 1: 0.5～2 gelatin and Tween 80.
Preferred 1: 30 of the volume ratio of oil phase and water.
The mean diameter of capsicine micro spheres is 2～38 μ m.
Preferred 3～10 μ m of the mean diameter of capsicine micro spheres.
The medicine carrying quality of capsicine micro spheres is 1.32%～27.67%.
The medicine carrying quality optimization 10%～20% of capsicine micro spheres.
The envelop rate of capsicine micro spheres is 6.60～84.52%.
Beneficial effect of the present invention:
(1) capsaicin has its unique analgesic activity and mechanism of action, can not produce gastrointestinal reaction, gastric ulcer, gastrorrhagia and the allergy etc. of NSAID, does not also have the addiction property of opiate receptor excitomotor, is a kind of new type analgesic;
(2) mostly at present commercially available is Fructus Capsici frost and hot pepper paste, need repeat administration every day for several times, and zest is bigger; And do not see the relevant report of relevant capsicine micro spheres, the capsaicin sustained-release micro-spheres of the present invention's preparation, topical can be avoided first pass effect of hepar; Prolong half-life improves its bioavailability, reduces zest; And can slowly continue to discharge medicine, and reduce administration number of times and dosage, reduce toxicity.Improve patient's compliance.
(2) because capsaicin can have been participated in numerous physiology and pathological process in vivo; Can select different route of administration after being made into microsphere; Like oral, injection (intravascular injection, intramuscular injection, subcutaneous injection, joint cavity injection), heeling-in etc.; Not only can be used for analgesia, can be used for simultaneously antiinflammatory, antibacterial, antipruritic, promote lipid metabolism, drug rehabilitation, inducing apoptosis of tumour cell, blood pressure lowering and treat some epithelial cell growth disease to have the very big prospect of marketing.
Description of drawings
Fig. 1 is the capsicine micro spheres stereoscan photograph.
Fig. 2 is a capsicine micro spheres cumulative in vitro release percentage diagram.
The specific embodiment
Below in conjunction with specific embodiment the present invention is further described.
Precision takes by weighing a certain amount of capsaicin and carrier material, join in the organic solvent of certain volume, behind the ultrasonic dissolution as oil phase.With the aqueous solution that contains a certain amount of emulsifying agent as water.Control certain temperature and mechanical agitation speed, oil phase is joined aqueous phase.The emulsifying continued stirs solvent flashing, and the centrifugal 5min of 3000rpm goes supernatant to collect microsphere, adds distilled water wash 3 times, centrifugal collection lyophilization.The concrete formulation and technology of embodiment 1-32 and the microsphere average grain diameter that makes, drug loading and envelop rate such as table 1.
Mean diameter, drug loading and the envelop rate of table 1 embodiment 1-32 capsicine micro spheres
External release experiment
Accurately take by weighing 4 parts of the capsicine micro spheres 25mg of embodiment 1 preparation respectively, in the bag filter of anticipating of packing into, add 1mL release medium solution; Tighten at two ends; Put into the tool plug vial that contains the 500mL release medium, place 37 ℃,, regularly (1,2,3,4,5,7,10,12d) sampling 2.0mL with the water bath with thermostatic control agitator of 75rpm speed jolting; Filter immediately (0.45 μ m), and add the fresh release medium of 2.0mL.Gained filtrating is carried out HPLC measures, calculate total release percentage (Q) according to standard curve, with Q to time (t) mapping (accompanying drawing 2).The capsicine micro spheres of preparation continues release 12 days, has tangible slow release effect, and does not have burst effect.The capsicine micro spheres of embodiment 2-32 preparation also has tangible slow release effect through experiment, and does not have burst effect.
Claims (7)
1. preparation method of capsicine micro spheres, its characteristic comprises the steps:
(1) in 27-100mg: the ratio of 100-250mg: 2-5mL is dissolved in capsaicin and carrier material and obtains oil phase in the organic solvent;
(2) with emulsifiers dissolve in water as water, said emulsifying agent is 5～30mg/mL in the concentration of aqueous phase;
(3) at 20 ℃～30 ℃, mixing speed is under the condition of 500～1200rpm, is 1: 20～1: 40 ratio by volume; Said oil phase is added said aqueous phase, form O/w emulsion, continue to stir the volatilization organic solvent; Centrifugal collection microsphere; Use distilled water wash, capsicine micro spheres is processed in lyophilization; Said carrier material is polylactic acid or polylactic-co-glycolic acid; Said organic solvent is that dichloromethane, ethyl acetate or volume ratio are 1: 1.5～9 the acetone and the mixed solvent of dichloromethane; Said emulsifying agent is that gelatin, polyvinyl alcohol or mass ratio are 1: 0.5～2 gelatin and Tween 80.
2. preparation method of capsicine micro spheres according to claim 1, the volume ratio that it is characterized in that said oil phase and water is 1: 30.
3. preparation method of capsicine micro spheres according to claim 1, the mean diameter that it is characterized in that said capsicine micro spheres are 2～38 μ m.
4. preparation method of capsicine micro spheres according to claim 3, the mean diameter that it is characterized in that said capsicine micro spheres are 3～10 μ m.
5. preparation method of capsicine micro spheres according to claim 1, the medicine carrying quality that it is characterized in that said capsicine micro spheres is 1.32%～27.67%.
6. preparation method of capsicine micro spheres according to claim 5, the medicine carrying quality that it is characterized in that said capsicine micro spheres is 10%～20%.
7. preparation method of capsicine micro spheres according to claim 1, the envelop rate that it is characterized in that said capsicine micro spheres is 6.60～84.52%.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103933016B (en) * | 2014-04-09 | 2016-04-13 | 江苏大学 | A kind of capsaicin ternary nano micelle and method for making thereof and purposes |
| CN104127383B (en) * | 2014-06-25 | 2016-08-10 | 江苏大学 | A kind of hollow silica nano controlled-release preparation being loaded with capsaicin and preparation method thereof |
| CN104083340B (en) * | 2014-07-29 | 2017-01-18 | 厦门大学 | Method for preparing tretinoin embedded polylactide drug-loaded microsphere |
| CN104548070B (en) * | 2015-01-19 | 2016-08-24 | 常州亚当生物技术有限公司 | Compound recipe capsaicin Emulsion is in the application for the treatment of skin trauma |
| CN105815771B (en) * | 2016-03-18 | 2019-04-09 | 浙江工业大学 | A kind of preparation method of erinacine/PLGA microballoon |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101108165A (en) * | 2007-07-11 | 2008-01-23 | 中国人民武装警察部队医学院 | Capsicine microemulsion and microemulsion gel rubber |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101108165A (en) * | 2007-07-11 | 2008-01-23 | 中国人民武装警察部队医学院 | Capsicine microemulsion and microemulsion gel rubber |
Non-Patent Citations (1)
| Title |
|---|
| 薛敏等.乳酸-羟基乙酸共聚物微球的研究进展.《齐鲁药事》.2007,第26卷(第4期),228-232. * |
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