CN101773475A - Preparation method of capsicine micro spheres - Google Patents
Preparation method of capsicine micro spheres Download PDFInfo
- Publication number
- CN101773475A CN101773475A CN201010031359A CN201010031359A CN101773475A CN 101773475 A CN101773475 A CN 101773475A CN 201010031359 A CN201010031359 A CN 201010031359A CN 201010031359 A CN201010031359 A CN 201010031359A CN 101773475 A CN101773475 A CN 101773475A
- Authority
- CN
- China
- Prior art keywords
- capsicine
- micro spheres
- preparation
- water
- micro
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
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 preparation method of capsaicin alkali microsphere.
Background technology
Capsaicin (Capsaicin) is to extract a kind of Rhizoma et radix valerianae amide alkaloid that obtains from natural capsicum, its chemical structure names is: N-[(4-hydroxyl-3-methoxyl group-phenyl)-and methyl]-8-methyl-(instead)-6-nonene amide, can obtain by 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 by 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 it is 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 made 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, can replace dolantin to use.
But the first pass effect of hepar that has height because of capsaicin, half-life is too short, oral administration biaavailability is also lower, capsaicin adopts the topical dosage form mostly at present, as cream, patch, ointment, membrane and cataplasma etc., but skin irritation is in various degree arranged all, as the skin scorch pain sense, congested and the neurogenic inflammatory reaction of regional area, limited its clinical practice, 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 by 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.The problem that in process of clinical application, exists in view of capsaicin, the present invention intends adopting macromolecular material parcel capsaicin to prepare the biological degradability sustained-release micro-spheres, avoid first pass effect of hepar, reduce 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 by 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, by 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 feature 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, described 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, be 1: 20～1: 40 ratio by volume, described oil phase is added described aqueous phase, form O/w emulsion, continue to stir the volatilization organic solvent, centrifugal collection microsphere, use distilled water wash, capsicine micro spheres is made 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 of opiate receptor excitomotor, is a kind of new type analgesic;
(2) present commercially available Fructus Capsici frost and the hot pepper paste of mostly being, need repeat administration every day for several times, and zest is bigger, and does 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, and prolong half-life improves its bioavailability, reduce 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 participate in numerous physiology and pathological process in vivo, can select different route of administration after being made into microsphere, as 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
The present invention is further illustrated below in conjunction with specific embodiment.
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.Continue to stir solvent flashing after the emulsifying, 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, pack in the bag filter of anticipating, 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 filtrate 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 (10)
1. preparation method of capsicine micro spheres, its feature 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, described 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, be 1: 20～1: 40 ratio by volume, described oil phase is added described aqueous phase, form O/w emulsion, continue to stir the volatilization organic solvent, centrifugal collection microsphere, use distilled water wash, capsicine micro spheres is made in lyophilization.
2. a kind of preparation method of capsicine micro spheres according to claim 1 is characterized in that described carrier material is polylactic acid or polylactic-co-glycolic acid.
3. preparation method of capsicine micro spheres according to claim 1 is characterized in that organic solvent is that dichloromethane, ethyl acetate or volume ratio are 1: 1.5～9 the acetone and the mixed solvent of dichloromethane.
4. preparation method of capsicine micro spheres according to claim 1 is characterized in that at described emulsifying agent being that gelatin, polyvinyl alcohol or mass ratio are 1: 0.5～2 gelatin and Tween 80.
5. preparation method of capsicine micro spheres according to claim 1, the volume ratio that it is characterized in that described oil phase and water is 1: 30.
6. preparation method of capsicine micro spheres according to claim 1, the mean diameter that it is characterized in that described capsicine micro spheres are 2～38 μ m.
7. preparation method of capsicine micro spheres according to claim 6, the mean diameter that it is characterized in that described capsicine micro spheres are 3～10 μ m.
8. preparation method of capsicine micro spheres according to claim 1, the medicine carrying quality that it is characterized in that described capsicine micro spheres is 1.32%～27.67%.
9. preparation method of capsicine micro spheres according to claim 8, the medicine carrying quality that it is characterized in that described capsicine micro spheres is 10%～20%.
10. preparation method of capsicine micro spheres according to claim 1, the envelop rate that it is characterized in that described capsicine micro spheres is 6.60～84.52%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010100313597A CN101773475B (en) | 2010-01-14 | 2010-01-14 | Preparation method of capsicine micro spheres |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010100313597A CN101773475B (en) | 2010-01-14 | 2010-01-14 | Preparation method of capsicine micro spheres |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101773475A true CN101773475A (en) | 2010-07-14 |
| CN101773475B CN101773475B (en) | 2012-05-30 |
Family
ID=42510152
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010100313597A Expired - Fee Related CN101773475B (en) | 2010-01-14 | 2010-01-14 | Preparation method of capsicine micro spheres |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101773475B (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103933016A (en) * | 2014-04-09 | 2014-07-23 | 江苏大学 | Capsaicin ternary nanomicelle as well as preparation method and application thereof |
| CN104083340A (en) * | 2014-07-29 | 2014-10-08 | 厦门大学 | Method for preparing tretinoin embedded polylactide drug-loaded microsphere |
| CN104127383A (en) * | 2014-06-25 | 2014-11-05 | 江苏大学 | Hollow silica nano sustained-release preparation loaded with capsicine, and preparation method thereof |
| CN104548070A (en) * | 2015-01-19 | 2015-04-29 | 常州亚当生物技术有限公司 | Application of compound capsaicin emulsion in treating skin wounds |
| CN105815771A (en) * | 2016-03-18 | 2016-08-03 | 浙江工业大学 | Preparation method of erinacine/PLGA microsphere |
| CN117883414A (en) * | 2024-03-18 | 2024-04-16 | 山东第二医科大学 | Long-acting slow-release capsaicin microsphere, and preparation method and application thereof |
| CN117883414B (en) * | 2024-03-18 | 2024-06-21 | 山东第二医科大学 | Long-acting slow-release capsaicin microsphere, and preparation method and application thereof |
Family Cites Families (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 |
-
2010
- 2010-01-14 CN CN2010100313597A patent/CN101773475B/en not_active Expired - Fee Related
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103933016A (en) * | 2014-04-09 | 2014-07-23 | 江苏大学 | Capsaicin ternary nanomicelle as well as preparation method and application thereof |
| 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 |
| CN104127383A (en) * | 2014-06-25 | 2014-11-05 | 江苏大学 | Hollow silica nano sustained-release preparation loaded with capsicine, and preparation method thereof |
| 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 |
| CN104083340A (en) * | 2014-07-29 | 2014-10-08 | 厦门大学 | Method for preparing tretinoin embedded polylactide drug-loaded microsphere |
| CN104548070A (en) * | 2015-01-19 | 2015-04-29 | 常州亚当生物技术有限公司 | Application of compound capsaicin emulsion in treating skin wounds |
| 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 |
| CN105815771A (en) * | 2016-03-18 | 2016-08-03 | 浙江工业大学 | Preparation method of erinacine/PLGA microsphere |
| CN105815771B (en) * | 2016-03-18 | 2019-04-09 | 浙江工业大学 | A kind of preparation method of erinacine/PLGA microballoon |
| CN117883414A (en) * | 2024-03-18 | 2024-04-16 | 山东第二医科大学 | Long-acting slow-release capsaicin microsphere, and preparation method and application thereof |
| CN117883414B (en) * | 2024-03-18 | 2024-06-21 | 山东第二医科大学 | Long-acting slow-release capsaicin microsphere, and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101773475B (en) | 2012-05-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101247795B (en) | Methods and compositions for treatment of CNS disorders | |
| CN101773475B (en) | Preparation method of capsicine micro spheres | |
| CN104447777B (en) | A kind of capsaicin-camptothecin cancer therapy drug conjugate and its preparation method and application | |
| CN108771657A (en) | A kind of small-molecule drug original position phase change gel slow-released system and preparation method thereof | |
| CN103417505B (en) | There is huperzine controlled release preparation of two-phase drug release behavior and preparation method thereof | |
| CN101703482B (en) | Galanthamine long-acting release injectable microsphere composite and preparation method thereof | |
| CN102558391A (en) | Vitamin E succinate-chitosan graft and preparation method and application thereof | |
| CN101926779A (en) | Gemcitabine solid lipid nanospheres, preparation method thereof and use thereof | |
| CN105456200B (en) | A kind of preparation method and application for the nano mciroball improving insoluble drug oral administration biaavailability | |
| CN102764426B (en) | Scorpion venom protein polypeptide colon-targeted preparation and preparation method thereof | |
| CN102525876A (en) | Aspirin solid dispersion, as well as preparation method, pharmaceutical composition and use thereof | |
| CN103830170B (en) | Ivermectin is at body gel injection and preparation method thereof | |
| CN103191119A (en) | Use of itraconazole in inhibiting of Akt kinase (protein kinase B) activity | |
| CN103690473B (en) | A kind of sinomenine preparation and preparation method thereof | |
| CN102993200B (en) | Paliperidone amino-acid ester and preparation method thereof | |
| CN100544738C (en) | A kind of antineoplastic Chinese medicine preparation | |
| CN101708175A (en) | Sustained release microsphere medicinal preparation using PHBHHx as carrier and method for preparing same | |
| CN103638060A (en) | Parischnogaster spp vespo bee venom polypeptide effective part and preparation and medical application thereof | |
| CN104497167B (en) | Hyaluronic acid derivative and therapeutic thereof | |
| CN106333969A (en) | Agaricus gennadii HDAC1 enzyme inhibition effective part and preparation method and application | |
| CN101721380A (en) | Method for preparing sustained-release preparation | |
| CN104926754A (en) | Rhein derivant and application thereof | |
| CN101062040B (en) | Stable type cucurbitacin liquid formula and the agent thereof | |
| CN105175285A (en) | Multiple target point type Tamibarotene derivative as well as preparation method and application thereof | |
| CN110478384B (en) | Method for extracting total coumarins from radix Saposhnikoviae, and its application in preparing composition for enhancing drug effect of central nervous system |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| ASS | Succession or assignment of patent right |
Owner name: MEDICAL COLLEGE OF CAPF Free format text: FORMER OWNER: MEDICAL COLLEGE, CHINESE PEOPLE'S ARMED POLICE FORCES Effective date: 20111117 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20111117 Address after: 300162 Tianjin City Hedong District Forest Road No. 222 Applicant after: Logistics College of Chinese Armed Police Force Address before: 300162 Tianjin City Hedong District Forest Road Medical College of Armed Police Applicant before: Medical College, Chinese People's Armed Police Forces |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20120530 Termination date: 20160114 |