CN1709444A - Tibetan medicine for relieving pain and its preparing method - Google Patents

Tibetan medicine for relieving pain and its preparing method Download PDF

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CN1709444A
CN1709444A CN 200510080694 CN200510080694A CN1709444A CN 1709444 A CN1709444 A CN 1709444A CN 200510080694 CN200510080694 CN 200510080694 CN 200510080694 A CN200510080694 A CN 200510080694A CN 1709444 A CN1709444 A CN 1709444A
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medicine
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preparation
emplastrum
parts
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CN100389799C (en
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雷菊芳
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Gansu Qizheng Tibetan Medicine Co Ltd
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Gansu Qizheng Tibetan Medicine Co Ltd
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Abstract

The present invention relates to a Chinese Tibet medicine for alleviating pain and its preparation method. Said preparation method includes the following steps: mixing the Chinese medicinal materials of aconitum pendulum, speranskia/balsam, dahurian angelica root, cranesbill, Zushima, saffron, frankincense and myrrh; grinding them to obtain crude powder; concentrating extract obtained by extracting the above-mentioned crude powder with ethyl alcohol to obtain extractum; then making the extractum into any dosage form, in particular, making it into plaster preparation, ointment preparation, spray, gell preparation and film preparation. Said plaster preparation can be used for curing the diseases of rheumatism, rheumatoid disease, traumatic injuries and neuralgia, etc. and can obtain obvious therapeutic effect.

Description

A kind of analgesic Tibetan medicine and preparation method thereof
Technical field
The present invention relates to a kind of analgesic drug product, specifically a kind of is the plaster of feedstock production with the Chinese herbal medicine.
Background technology
Chronic lumbar muscle strain, scapulohumeral periarthritis, hyperosteogeny, rheumatic arthritis, rheumatoid arthritis and soft tissue are frustrated, are sprained etc. and be mostly the chronic pain disease that some are common.Wherein rheumatism, rheumatoid disease belong to the difficult problem on the world medicine, are called " not dead cancer " by medical circle, and the sickness rate height has chronic, easy recurrence, characteristics that disability rate is high.Any age all can fall ill, but is mainly in 20-60 year.
Add up according to World Health Organization (WHO), whole world rheumatism, annual about 8,000 ten thousand people of rheumatoid patient, prevalence is more than 1%, with the U.S. is example, general North America crowd's rheumatoid arthritis prevalence is about 1%, the American Indian is then up to 5%~6%, part U.S. area more than 60 years old crowd's sickness rate reach 10%.Because of suffering from the patient that this type of disease disables nearly 1,000 ten thousand people just there is every year.
According to Ministry of Public Health statistics, China's rheumatism, rheumatoid patient be up to 2,000 ten thousand people, and have 1st/10th, the patient with severe symptoms.At present, this type of disease is the 4th of suffering from chronic diseases of Lie Ju China urban and rural residents, and also about 1%, 80% patient's age of onset is in 20-45 year for sickness rate, and men and women's ratio is 1: 2.4.Be mainly in North China, the Northeast of China, sickness rate is more than 1%, and the women is more than the male.
Along with the quickening of aged tendency of population, also can present the trend that increases year by year in rheumatism, the rheumatoid patient's number world wide, therefore, market potential is huge.
At present, treat this type of disease both at home and abroad and also do not have medicine or preparation preferably.
The Western medicine medicine of treatment rheumatism, rheumatoid disease mainly contains three classes:
The first kind: the non-steroidal anti-inflammatory drug thing has faster analgesic antiphlogistic effect.Comprise various anti-inflammatory drugs, domestic Indocid commonly used, Feldene, Voltaren, Relifex, Naproxen, Sulindac, Surgem, Tilcotil etc. respectively have its characteristic and pluses and minuses.But above medicine generally has the side effect that causes " gastric ulcer and gastropathy ".
Second class: comprise numerous disease modification antirheumatic, be regarded as to improve the medicine of the state of an illness at all.Just brought test as far back as the twentieth century initial stage, be to use the historical famous medicine of the longest and tool clinical experience of experience.It can slow down or suppress proceeding of the course of disease, and is effective for serious progressive rheumatoid arthritis, if result of use is better in early days.But its side effect is quite a few, common as flushing, scratch where it itches, the golden lung disease of oral ulcer, headache, dizziness, leukopenia, thrombocytopenia, nephrotoxicity and less generation.The main medicine of representing has two kinds of Thiomalate (trade name Shiosol) and Aurathioglucose (trade name Solganol).
Anabolic agent: can merge first line or the second line drug use, can be oral, injection or intraarticular injection.This class medicine can alleviate extremely serious arthritic symptom effectively, be most commonly used to treat the carrying out property arthritis that traditional treatment is invalid or be difficult to cure, but often bring many side effect such as liquid and electrolyte imbalance, the intestines and stomach, endocrine, eyes and metabolic damage, and typical moon face.Short-term uses then rare side effect to take place, but can not reach the purpose of treatment fully.
This type of disease of Chinese patent drugs for treatment, though kind of medicine surplus having 120, dosage form mostly is traditional medicated wine, pill etc., the course of treatment is longer, can alleviate, improve symptom.But drug toxicity is big, and effective dose and toxic dose are comparatively approaching, and the drug safety scope is narrower, along with dosage increases, though curative effect has raising, and the also corresponding increase of toxicity.
Summary of the invention
The objective of the invention is to overcome the shortcoming of existing medicine, provide that a kind of cost is low, good analgesic effect, medicament composing prescription that toxic and side effects is little and preparation method thereof.
Analgesic drug product of the present invention is the medicament of being made by the following portions by weight raw material:
Radix aconiti szechenyiani 20-60 part Herba speranskiae tuberculatae 5-30 part Radix Angelicae Dahuricae 5-20 part Herba Erodii 5-30 part Daphne giraldii Nitsche 1-20 part Flos Carthami 1-10 part Olibanum 2-15 part Myrrha 2-15 part
The formula optimization weight proportion scope of medicine of the present invention is:
Radix aconiti szechenyiani 30-50 part Herba speranskiae tuberculatae 10-20 part Radix Angelicae Dahuricae 6-14 part Herba Erodii 10-18 part Daphne giraldii Nitsche 3-8 part Flos Carthami 3-8 part Olibanum 3-8 part Myrrha 3-8 part
The percentage by weight of the optimum material proportion of medicine of the present invention is:
Radix aconiti szechenyiani: 45 parts of Herba speranskiae tuberculataes: 15 parts of Radixs Angelicae Dahuricae: 10 portions of Herba Erodiis: 5 parts of Flos Carthamis of 15 parts of Daphne giraldii Nitsche: 5 parts of Olibanums: 5 parts of Myrrhas: 5 parts
Described medicament is any dosage form on the pharmaceutics, is preferably emplastrum, ointment, spray, gel or liniment.[" pharmacy of Chinese materia medica " (using), Shanghai science tech publishing house, in December, 1997 front page for Chinese medicine class specialty; " pharmaceutical preparation research and development and production new technique technology are used complete works of ", the contemporary China audio ﹠ video press.]
Process for preparing medicine of the present invention comprises following process:
Medicine is ground to form coarse powder, use the 60-90% ethanol percolation, extracting solution simmer down to extractum or with 60-90% alcohol reflux 1-3 time (being preferably 2-3 time), each 0.5-2 hour (being preferably 0.5-1.5 hour), extracting solution simmer down to extractum, other gets caouttchouc 10-100 part (being preferably 20-80 part); Zinc oxide 10-100 part (being preferably 20-80 part); Colophonium 3-50 part (being preferably 5-30 part); Lanoline 0.5-15 part (being preferably 1-10 part); Vaseline 0.1-10 part (being preferably 0.5-5 part); Liquid paraffin 0.1-10 part (being preferably 0.5-5 part) is mixed and made into substrate, in the extractum adding substrate with said extracted, makes coating, is coated with cream, cuts off, and the lid lining is cut into small pieces, and promptly gets plaster.
The host material that plaster of the present invention is used makes by known technology: such as " technical study of compound recipe pinellia tuber for relieving cough emplastrum "
The present invention can also directly make ointment, spray, gel or liniment product with the extractum that obtains by known technology.
Advantage of the present invention and effect:
The present invention is based on traditional Tibetan medicine and pharmacology theory, and in conjunction with clinical experience for many years, prescription forms.
Traditional medical science that Tibetanmedicine is a reason, method, side, medicine is very complete, it is theoretical core with the theory on three categories of etiologic factors, is guiding theory with five source theories, based on the physiology of seven materials, three dirty things and internal organs meridians, the theory of medicine system of pathology theory.Tibetan medicine is exactly one of the external therapy that comprehensively embodies the uniqueness of its theoretical system and medicine characteristics, and on the medical knowledge basis of long-term accumulation, combine with the external therapy of medicine gradually, the branch that develops into pharmacotherapy through clinical practice in 1,100 has characteristics such as easy, applied widely.Because external treatment directly acts on diseased region, instant effect, no pain not only has therapeutical effect, also has advantages such as cleaning, prevention, health care simultaneously, thus enjoy the attention and the high praise of ancient Chinese medicine doctor, and follow the development of motherland's medical science surgery and maturation.
Plaster of the present invention is compared with dosage form with aforesaid existing Chinese and western drugs, owing to adopt natural medicinal formulations, toxic and side effects is little, detect proof by a large amount of clinical efficacies, plaster of the present invention has the effect that reduces or eliminate RE (rheumatoid factor), evident in efficacy to treatment rheumatism, rheumatoid, osteopatia sprain, neural all pains, and cost is low, easy to use.
One, following is clinical operating position and result:
Treatment group: the plaster that medicament composing prescription of the present invention is made according to conventional method.
Matched group: SHANGSHI ZHITONG GAO.
Usage and dosage: external, be affixed on the affected part, changed once in per 24 hours.
Function cures mainly: expelling wind and removing dampness, promoting blood circulation and stopping pain.Be used for anemofrigid-damp arthralgia, arthralgia, osteopatia sprain, neural all pain diseases.
(1) case situation: treatment is organized 51 examples and is the outpatient, and the age is in 17-70 year, male's 19 examples wherein, and women's 32 examples are observed rheumatic arthritis 28 examples, rheumatoid arthritis 9 examples, scapulohumeral periarthritis 4 examples, arthritis muscle injury 4 examples, other osteoarthritis 6 examples.For proving this plaster curative effect, the matched group that sticks SHANGSHI ZHITONG GAO is set simultaneously: observe 10 examples altogether, wherein a part is according to the effect of previously using SHANGSHI ZHITONG GAO, and the ointment that another part is used two kinds of plaster respectively to ill symmetrical joint of while compares.
(2) observational technique:
All case all auspicious inquiry medical history and health check-ups before treatment, some cases is also made erythrocyte sedimentation rate, anti-" 0 " and rheumatoid factor inspection.The minority case is clapped arthrogram.For chronic phase case mainly observe the degree that sticks before the plaster of the present invention and finish the back pain relief course of treatment, and the front and back that only a few acute stage case is observed positive sign and laboratory data are simultaneously changed.
(3) administrated method:
Treatment group, matched group case are used ointment of the present invention and SHANGSHI ZHITONG GAO respectively, concrete using method: (1), whenever put up to apply and changed once in 24 hours; (2), to stick 4-5 time be a course of treatment at each position; (3), stick at most at every turn and be no more than 15 (anemia of pregnant woman and local diabrosis do not stick.)
(4) criterion of therapeutical effect
Recovery from illness---pain is eliminated fully or sign disappears.
Produce effects---pain or sign are obviously alleviated or are reached more than 75%.
Taking a turn for the better---pain or sign make moderate progress, and degree is lower than 50%.
Invalid---do not have and improve or the person of increasing the weight of;
(5) checking result
Recovery from illness 9 examples in 51 examples, produce effects 25 examples, 10 examples that take a turn for the better, invalid 7 examples, total effective rate 86.3%, cure-remarkable-effectiveness rate 66.7% are organized in treatment.Matched group 0 example of fully recovering, produce effects 2 examples, 5 examples that take a turn for the better, invalid 3 examples. cure-remarkable-effectiveness rate 20%, total effective rate 70%, each sick curative effect of planting sees Table 1.
The various curative effect statistical tables of table 1
Project The example number Recovery from illness Produce effects Take a turn for the better Invalid Effective percentage Cure-remarkable-effectiveness rate
Rheumatic arthritis ??28 ??7 ??15 ??5 ??1 ??96.4% ??78.6%
Rheumatoid arthritis ??9 ??0 ??3 ??3 ??3 ??66.6% ??33.3%
Scapulohumeral periarthritis ??4 ??1 ??1 ??1 ??1 ??75% ??50%
Osteoarthrosis, muscle sprain ??4 ??1 ??3 ??0 ??0 ??100% ??100%
Other osteoarthritis ??4 ??0 ??2 ??1 ??1 ??75% ??50%
Other ??2 ??0 ??1 ??0 ??1 ??50% ??50%
Add up to ??51 ??9 ??25 ??10 ??7 ??86.3% ??66.7%
Matched group ??10 ??0 ??2 ??5 ??3 ??70% ??20%
Sum up:
Prove treatment group cure-remarkable-effectiveness rate 66.7%, total effective rate 86.3%, matched group by clinical verification. cure-remarkable-effectiveness rate 20%, total effective rate 70%, treatment group curative effect is higher than matched group, illustrates that medicine of the present invention makes plaster and have significant therapeutical effect.
Two, pharmacodynamics test
(1) antiinflammatory test
1 emplastrum of the present invention to the influence of mice ear (Li Yikui etc., the herbal pharmacology experimental methodology, Science and Technology of Shanghai publishing house, 1991:298-300)
1.1 experiment material:
Animal: mice, the Kunming kind, male, in 6~8 weeks of age, body weight 18~22g provides quality certification SCXK (capital) 2002-0003 by Beijing dimension tonneau China laboratory animal technology company limited.
Medicine and reagent: the emplastrum that medicine of the present invention is made (0.88g crude drug/sheet) is provided lot number 20040801 by Gansu Qizheng Tibetan Medicine Co., Ltd; The prednisolone acetate injection, content 25mg/ml, Shanghai the 9th pharmaceutical factory, lot number 041002; Dehydrated alcohol, analytical pure, Beijing Chemical Plant, lot number 20010209; Ether, analytical pure, Red Star chemical plant, Beijing, lot number 990402.Electronic balance, LIBROR EB-280M-22, day island proper Tianjin instrument company.
1.2 method and result
50 of mices, stratified random is divided into matched group (giving substrate), the emplastrum height that medicine of the present invention is made, in, low dose group (0.586,0.293,0.174g crude drug/kg), with positive drug cortisone acetate group (0.025g/kg), wherein except that positive drug is the ip administration, all the other are percutaneous dosing, 3 days (every day 1 time) of successive administration, behind the last administration 1h, only smear 2% Oleum Tiglii (Oleum Tiglii: ethanol: the ratio of ether is 0.2: 2: 7.8), 50 μ l/ at the left side auricle, put to death behind the 4h,, weigh with the rustless steel blunderbuss blunderbuss bottom left auris dextra exterior feature of diameter 6mm, calculate the ear swelling rate, organize a t check.Ear swelling rate computing formula is as follows:
Ear swelling rate=(left ear weight-auris dextra is heavy)/auris dextra heavy * 100%
The results are shown in Table 2, the emplastrum height that medicine of the present invention is made, middle dosage group (0.586, the 0.293g crude drug/kg) the ear swelling rate all significantly is lower than matched group (P<0.05).
The emplastrum that table 2 medicine of the present invention is made is to the influence of mice ear (x ± s)
Group Number of animals (only) Dosage (the g crude drug/kg) Ear swelling rate (%)
The emplastrum prednisone acetate that the emplastrum medicine of the present invention that the emplastrum medicine of the present invention that control group medicine of the present invention is made is made is made ??10 ??10 ??10 ??10 ??10 ??-- ??0.586 ??0.293 ??0.174 ??0.025g/kg ??138.15±20.71 ??110.03±29.81* ??114.49±23.25* ??126.04±34.22 ??21.59±19.53**
Compare * P<0.05, * * P<0.01 with matched group
2, the emplastrum on Carrageenan made of medicine of the present invention causes the influence [1] of rat paw edema
2.1 experiment material
Animal: the SD rat, male, body weight 220~240g provides quality certification SCXK (capital) 2002-0003 by Beijing dimension tonneau China laboratory animal technology company limited.
Medicine and reagent: the emplastrum that medicine of the present invention is made (0.88g crude drug/sheet) is provided lot number 20040801 by Gansu Qizheng Tibetan Medicine Co., Ltd; Aspirin, content 95~105%, Xi'an Bo Hua Pharmaceutical Co, lot number 0302019; Carrageenin, Sigma company, lot number 121K1653.
2.2 method and result
50 of rats, stratified random be divided into the high, medium and low dosage group of emplastrum that matched group (give substrate), medicine of the present invention make (0.4,0.2,0.1g crude drug/kg) and positive drug aspirin group (0.1g/kg), except that positive drug is gastric infusion, be percutaneous dosing, 3 days (every day 1 time) of successive administration, behind the last administration 1h, carrageenin 100 μ l at its right hind foot sole of the foot portion subcutaneous injection 1%, respectively at injection back 1h, 2h, 4h, 6h miking swelling foot sole of the foot portion girth, calculate the foot swelling rate, organize a t check.Computing formula is as follows:
Figure A20051008069400081
The results are shown in Table 3, the emplastrum high dose group that medicine of the present invention is made (the foot swelling rate in rat paw subcutaneous injection carrageenin 4h of 0.4g crude drug/kg), (the 0.2g crude drug/kg) all significantly be lower than matched group (P<0.01 or P<0.05) of dosage group in the emplastrum that medicine of the present invention is made in rat paw subcutaneous injection carrageenin 2h foot swelling rate.
Table 3 emplastrum on Carrageenan of the present invention causes the influence (x ± s) of rat paw edema
Group Number of animals (only) Dosage (the g crude drug/kg) Foot swelling rate (%)
??1h ??2h ??4h
Matched group emplastrum of the present invention emplastrum of the present invention emplastrum aspirin of the present invention ??10 ??10 ??10 ??10 ??10 ??- ??0.4 ??0.2 ??0.1 ??0.1 ??24.8±9.9 ??14.1±8.5* ??19.4±5.7 ??19.9±4.9 ??14.2±5.9* ??32.5±11.3 ??17.5±8.4** ??22.5±7.1* ??24.6±5.4 ??22.8±6.2* ??22.1±11.2 ??12.0±7.7* ??15.9±6.6 ??18.8±5.6 ??16.1±6.6
Compare * * P<0.01, * P<0.05 with matched group.
(2) analgesic test
1, the emplastrum made of medicine of the present invention to the analgesic activity of the hot whipping of mice (Li Yikui etc., the herbal pharmacology experimental methodology, Science and Technology of Shanghai publishing house, 1991:351)
1.1 experiment material
Animal: mice, the Kunming kind, male, in 6~8 weeks of age, body weight 18~22g is provided by Beijing dimension tonneau China laboratory animal technology company limited, the quality certification number: SCXK (capital) 2002-0003.
Medicine and reagent: the emplastrum that medicine of the present invention is made (0.88g crude drug/sheet) is provided lot number 20040801 by Gansu Qizheng Tibetan Medicine Co., Ltd; Somedon, every contains aminophenazone 0.15g; Phenacetin 0.15g; Caffeine 0.05g; Phenobarbital 0.015g (0.365g/ sheet).Yongkang, Beijing pharmaceutcal corporation, Ltd, lot number, 03030283.
1.2 method and result
50 of mices, stratified random be divided into the high, medium and low dosage group of emplastrum that matched group (give substrate), medicine of the present invention make (0.586,0.293,0.174g crude drug/kg), wherein positive drug somedon group (0.365g/kg) is the oral administration gavage administration, and all the other are percutaneous dosing.Measure the threshold of pain (mice to the time that afterbody gets rid of, claims TFL after the administration in 50 ± 1 ℃ of warm water of tail point immersion) of each mice before the administration earlier with stopwatch, 1h behind the single-dose, 2h, 4h, 6h measure the TFL of each Mus respectively, calculate the analgesia rate, organize a t check.
The results are shown in Table 4, the high, medium and low dosage of the emplastrum that medicine of the present invention is made has significant analgesic activity to the hot whipping of mice.(comparing P<0.01, P<0.05 with matched group)
The emplastrum that table 4 medicine of the present invention is made is to the analgesic activity of the hot whipping of mice (x ± s)
Group Number of animals (only) Dosage (the g crude drug/kg) Analgesia rate (%)
???1h ? ???2h ? ???4h ? ? ???6h ?
The emplastrum somedon that the emplastrum medicine of the present invention that the emplastrum medicine of the present invention that control group medicine of the present invention is made is made is made ???10 ? ? ???10 ? ? ? ? ???10 ? ? ???10 ? ? ???10 ? ???-- ? ???0.586 ? ? ???0.293 ? ? ???0.174 ? ? ? ???0.365g/k ???g ???10.6±11 ???.7 ???28.0±17 ???.4* ? ???35.1±29 ???.7* ? ? ???18.1±15 ???.8 ? ???39.7±31 ???.0* ???2.8±4.5 ? ???46.9±21. ???8** ? ? ???30.9±28. ???6* ? ? ???31.5±37. ???0* ? ???26.3±11. ???5** ???6.1±8.5 ? ???58.2±36. ???7** ? ???63.5±29. ???1** ? ???41.7±32. ???3** ? ???28.7±13. ???8** ???4.0±6.5 ? ???18.8±18. ???3** ? ???25.4±13. ???9** ? ???25.9±21. ???7* ? ? ???16.6±22. ???2
Compare * P<0.05, * * P<0.01 with matched group.
2, the emplastrum made of medicine of the present invention to mouse peritoneal injection acetic acid cause pain influence (Qi Chen, the herbal pharmacology research method, the People's Health Publisher, 1993:307)
2.1 experiment material
Animal: mice, the Kunming kind, male, in 6~8 weeks of age, body weight 18~22g is provided by Beijing dimension tonneau China laboratory animal technology company limited, the quality certification number: SCXK (capital) 2002-0003.
Medicine and reagent: the emplastrum that medicine of the present invention is made (0.88g crude drug/sheet) is provided lot number 20040801 by Gansu Qizheng Tibetan Medicine Co., Ltd; Somedon, every contains aminophenazone 0.15g; Phenacetin 0.15g; Caffeine 0.05g; Phenobarbital 0.015g (0.365g/ sheet).Yongkang, Beijing pharmaceutcal corporation, Ltd, lot number, 03030283.
2.2 method and result
50 of mices, stratified random be divided into the high, medium and low dosage group of emplastrum that matched group (give substrate), medicine of the present invention make (0.586,0.293,0.174g crude drug/kg), positive drug somedon group (0.365g/kg), wherein positive drug is the oral administration gavage administration, all the other are percutaneous dosing.Behind the administration 4h, lumbar injection 0.7% acetum 0.2ml/ only, record is given behind the acetic acid and to be turned round the body number of times in the 15min.
The results are shown in Table 4, the emplastrum height that medicine of the present invention is made, middle dosage (0.586, the 0.293g crude drug/kg) Dichlorodiphenyl Acetate induced mice writhing response has remarkable inhibitory action, compares P<0.01 or P<0.05 with matched group.
The emplastrum that table 5 medicine of the present invention is made is to the influence of mice acetic acid twisting (x ± s)
Group Number of animals (only) Dosage (g/kg) Turn round the body number of times
The emplastrum somedon that the emplastrum medicine of the present invention that the emplastrum medicine of the present invention that control group medicine of the present invention is made is made is made ???10 ???10 ? ???10 ? ???10 ? ? ???10 ???- ???0.586 ? ???0.293 ? ???0.174 ? ???0.365 ???19.2±12.1 ???5.9±4.3** ? ???5.2±7.7** ? ???11.1±3.5 ? ???3.3±4.7**
Compare * P<0.05, * * P<0.01 with matched group.
(3). brief summary:
After the emplastrum percutaneous dosing that medicine of the present invention is made, can effectively suppress Oleum Tiglii and cause the mice ear inflammatory reaction, alleviate carrageenin and cause the inflammatory reaction of rat paw edema, can significantly alleviate the pain that mice thermostimulation and chemical irritation cause, show that the emplastrum that medicine of the present invention is made has good antiinflammatory, analgesic activity.
Three, acute toxicity test:
1.1 test sample
1.1.1 title: the emplastrum that medicine of the present invention is made.
Lot number: 20040801.
1.1.2 content or purity: contain Radix aconiti szechenyiani, Camphora, Borneolum Syntheticum etc.
Concentration: 0.88g crude drug/subsides.
1.1.3 physicochemical property: faint yellow emplastrum.
1.1.4 test sample stability and keeping
1.1.4.1 temperature: room temperature.
1.1.4.2 humidity: drying.
1.1.4.3 light: cool place.
1.1.4.4 preservation condition: room temperature lucifuge.
1.1.4.5 registration procedure: at every turn get quantity, date, the user of service of test sample, the equal registration record of application target.After research finished, remaining test sample was returned client.
1.2 research system
1.2.1 plant: rabbit
1.2.2 be: big ear is white
1.2.3 sex and quantity: male and female half and half, totally 16.
1.2.4 the weight of animals: 2.4-3.5kg.
1.2.5 animal origin: Beijing Vital River Experimental Animals Technology Co., Ltd.
1.2.6 animal credit number: SCXK (capital) 2002-0003.
1.2.7 explanation is selected by the research system: State Food and Drug Administration's " provisions for new drugs approval " regulation can be used rabbit, and rabbit is agreed to use by client.
1.2.8 research system marks program: after animal arrives, by the requirement reception of SOP.
1.2.9 raising condition: animal will be raised by the personnel that obtain Qualification Approval.Animal House is hung Hygrothermograph, early measures record 1 time every day during 8:30-9:00.Room temperature is controlled at 18-22 ℃, humidity 60 ± 20%, natural illumination.Clean cage house 1 time every day.
1.2.10 quarantine process: all animals will be by the SOP requirement, and quarantine was observed 7 days, at this moment between in, the disease and the dead indication of observing animal, any abnormal phenomena all needs to report to thematic director.Find that any ill animal rejects when laboratory animal is selected.According to situation before and after the quarantine as the main foundation selected.
1.2.11 feedstuff: with Beijing section Australia standard particle forage feed that feed corporation,Ltd provides of pulling together.Freely ingest.
1.2.12 dredge dish: feed with fresh carrot every day, the animal free choice feeding.
1.2.13 drinking water: supply ordinary water with china bowl, animal is freely drunk.
1.3 experimental design
1.3.1 the foundation of EXPERIMENTAL DESIGN
1.3.1.1 the human dosage that producer provides: paste the affected part, every day, 1-2 pasted, and 24h changes once.
1.3.1.2 the second original text .2004 of State Food and Drug Administration's " Chinese medicine, natural drug studies on acute toxicity technological guidance principle ".
Pertinent regulations in " study of tcm new drug instructs south " of Ministry of Public Health promulgation.
1.3.2 experiment grouping and medication: at first animal is carried out the skin of back depilation.Tame rabbit back is cut off long hair with shears, and an amount of depilatory (barium sulfide) was used warm water cleaning after 3-4 minute on the repaste.Depilation district area 10 * 15cm2 is divided into 4 groups with animal, 4 every group then at random.First group is the blank group, and second group is the emplastrum high dose group made of medicine of the present invention (2.64g crude drug/kg).The 3rd group is (the 0.88g crude drug/kg) of dosage group in the emplastrum made of medicine of the present invention.The 4th group is the emplastrum low dose group made of medicine of the present invention (0.293g crude drug/kg).Keep 24h after giving a medicine, observed continuously 7 days.
The making of damaged skin: after the depilation zone of rabbit is with iodine tincture and 75% alcohol disinfecting, skin cross method is scratched, make skin the petechia occur with the 7# syringe needle.The grouping medication is tested with intact skin.Observed 1,24,48,72 hour thereafter to the 7th day, the behavioral activity of animal, fur gloss, diet, body weight and death condition and with matched group relatively.
2.0 result:
2.1 general index observing: observed 7 days continuously after the administration, the emplastrum that medicine of the present invention is made time spent outside high dose, middle dosage and low dosage has no effect to behavior, activity, diet, the fur gloss of intact skin and damaged skin rabbit, the results are shown in Table 6 and table 7.
2.2 the weight of animals: after giving the emplastrum that medicine of the present invention makes, each treated animal body weight to intact skin and damaged skin of outer time spent of high dose, middle dosage and low dosage has no effect, and the results are shown in Table 8.
3.0 conclusion
The high, medium and low three dosage percutaneous drug deliveries of the emplastrum that medicine of the present invention is made do not have obvious acute toxic reaction to rabbit.
When the emplastrum that table 6 medicine of the present invention is made is used for the complete sum damaged skin to the influence of rabbit ordinary circumstance
(n=4)
Matched group Intact skin Damaged skin
High dose Middle dosage Low dosage High dose Middle dosage Low dosage
Hour behavioral activity diet fur gloss eye and mucosa are breathed other Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal-
24 hours behavioral activity diet fur gloss eyes and mucosa are breathed other Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal-
48 hours behavioral activity diet fur gloss eyes and mucosa are breathed other Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal-
72 hours behavioral activity diet fur gloss eyes and mucosa are breathed other Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal-
When the emplastrum that table 7 medicine of the present invention is made is used for the complete sum damaged skin to the influence of rabbit ordinary circumstance
(n=4)
Matched group Intact skin Damaged skin
High dose Middle dosage Low dosage High dose Middle dosage Low dosage
The 4th day behavioral activity diet fur gloss eye and mucosa are breathed other Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal-
The 5th day behavioral activity diet fur gloss eye and mucosa are breathed other Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal-
The 6th day behavioral activity diet fur gloss eye and mucosa are breathed other Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal-
The 7th day behavioral activity diet fur gloss eye and mucosa are breathed other Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal- Normal smoothness-normal-
When the emplastrum that table 8 medicine of the present invention is made is used for the complete sum damaged skin to the influence of rabbit body weight (x ± s,
n=4)
Group Dosage (the g crude drug/kg) Body weight (kg)
Before the administration After the administration
Intact skin matched group Radix aconiti szechenyiani Radix aconiti szechenyiani Radix aconiti szechenyiani ??- ??2.64 ??0.88 ??0.293 ??2.78±0.35 ??2.80±0.28 ??2.90±0.22 ??2.83±0.26 ??2.85±0.47 ??2.83±0.15 ??3.03±0.22 ??2.85±0.37
Damaged skin matched group Radix aconiti szechenyiani Radix aconiti szechenyiani Radix aconiti szechenyiani ??- ??2.64 ??0.88 ??0.293 ??2.85±0.47 ??2.83±0.15 ??3.03±0.22 ??2.85±0.37 ??3.05±0.44 ??3.10±0.08 ??3.30±0.24 ??3.05±0.44
Four, long term toxicity test:
4.1 test sample and reference substance
4.1.1 test sample title: the emplastrum that medicine of the present invention is made.
4.1.2 lot number: 20040801
4.1.3 content or purity: contain Radix aconiti szechenyiani, Camphora, Borneolum Syntheticum etc.0.88g crude drug/subsides.
4.1.4 physicochemical property: flaxen emplastrum.
4.1.5 test sample stability and keeping.
4.1.5.1 temperature: cool place.
4.1.5.2 humidity: drying.
4.1.5.3 light: lucifuge.
4.1.5.4 stability: 3 years shelf-lifves.
4.1.5.5 preservation condition: room temperature, lucifuge.
4.1.6 registration procedure: quantity, date, user of service, the application target of at every turn getting test sample all registered on record, and after research finished, remaining test sample was returned client.
4.2 research system
4.2.1 plant: Cavia porcellus
4.2.2 be:
4.2.3 sex and quantity: male and female half and half, 10 every group, totally 40.
4.2.4 animal age: grow up.
4.2.5 the weight of animals: ♂ 288.2 ± 22.4, ♀ 258.7 ± 29.3g.
4.2.6 animal origin: Beijing Vital River Experimental Animals Technology Co., Ltd..
The quality certification number: SCXK (capital) 2002-0003.
4.2.7 explanation is selected by the research system: Cavia porcellus is one of the recognized standard animal in the toxicologic study.This kind animal is recommended to use by China's " provisions for new drugs approval ".The consigner agrees to use this kind animal.
4.2.8 research system marks program: after animal arrives, by the requirement reception of SOP AS034.Determine the serial number of independently quarantining for every animal.Be that every animal is specified the single number of zoologizeing during grouping.Indicate animal number on animal and the cage card.Use the number of zoologizeing to discern in the raw data.
4.2.9 raising condition: animal feeding is in the one-level Animal House, and 5 in every cage is raised by the personnel that obtain Qualification Approval.Record room temperature, humidity are controlled room temperature at 20-24 ℃ every day, and humidity is at 40-70%, and every day, cleaning was changed clothes the cage chassis 1 time, and cleaned at regular intervals is changed the cage tool.
4.2.10 quarantine process: all animals will be by SOP AS035 requirement, and quarantine was observed more than 1 week, at this moment between in, the disease and the dead indication of observing animal, any abnormal phenomena is all to thematic director's report.Animal is before use through thematic director's approval.Find that any ill animal rejects when laboratory animal is selected.As if occurring morbid state before the animals administer or losing weight, under instructing, thematic director replaces with healthy animal.
4.2.11 feedstuff: with pull together standard Cavia porcellus special feed that feed corporation,Ltd provides and add fresh carrot and feed of Beijing section Australia.Freely ingest fasting>16h before the blood-sample withdrawal.
4.2.12 drinking water:, freely drink by animal with drinking-water bottle supply ordinary water.
4.3 experimental design
4.3.1 the foundation of EXPERIMENTAL DESIGN
4.3.1.1 acute toxicity test data: rabbit by 2.64,0.88,0.293g crude drug/kg administration, be 90,30,10 times of people's consumption, non-toxic reaction as a result.
4.3.1.2 animal drug effect dosage data: mouse corrosion disease, analgesic dose are 0.586,0.293,0.159g crude drug/kg, and curative effect is obvious.Rat antiinflammatory dosage is 0.4,0.2g crude drug/kg, determined curative effect.
4.3.1.3 the clinical application scheme that client provides: the emplastrum that medicine of the present invention is made, every subsides contain crude drug 0.88g, paste with 2 at every turn.Press maximum dose level and calculate, people's consumption per day is 0.0293g crude drug/kg
The course of treatment:<two weeks.
4.3.1.4 the second original text .2004 of State Food and Drug Administration's " Chinese medicine, natural drug long term toxicity investigative technique guideline ".
Pertinent regulations in the bureau of drug policy ﹠ administration of Ministry of Health of the People's Republic of China " study of tcm new drug guide ".
4.3.2 the experiment grouping: according to test objective and EXPERIMENTAL DESIGN requirement, basic, normal, high three the dosage groups of emplastrum that medicine of the present invention is made are established in this test, and other establishes the blank group.Each is organized dosage and intends seeing the following form with the relation of dosage multiple with the people.
The emplastrum Cavia porcellus percutaneous dosing that table 9 medicine of the present invention is made a toxicity test dosage design in month
Group Dosage (the g crude drug/kg) Be equivalent to the people and intend using the dosage multiple Number of animals
?????♂ ?????♀
I group matrix contrast II organizes the low III of emplastrum that medicine of the present invention makes and organizes that IV organizes the emplastrum height that medicine of the present invention is made in the emplastrum that medicine of the present invention makes ?????0 ?????0.44 ? ?????0.88 ? ?????1.76 ? ?????0 ?????15 ? ?????30 ? ?????60 ? ?????5 ?????5 ? ?????5 ? ?????5 ? ?????5 ?????5 ? ? ?????5 ? ?????5 ?
4.3.3 test sample gives approach and number of times:
Route of administration: percutaneous dosing.
1.76,0.88,0.44g crude drug/kg body weight/d dosage:.
Administration time: 9:00-10:00 administration in the morning.
The administration time limit: one month.
4.3.4 give the approach explanation of test sample: consistent with the clinical application approach.
4.3.5 the preparation of test sample and reference substance:
Matched group: blank is not for containing the substrate of medicine.
Test sample: high, medium and low three the dosage groups of the emplastrum that medicine of the present invention is made all adopt the different area administration.
The emplastrum that medicine of the present invention is made contains 0.88g crude drug/subsides.
4.3.6 giving of test sample: guinea pig back is cut off long hair with shears earlier, and an amount of depilatory (barium sulfide) was used warm water cleaning after 3-4 minute on the repaste.Emplastrum height, middle dosage that medicine of the present invention is made are applied to Cavia porcellus depilation zone, and the emplastrum low dosage that medicine of the present invention is made is affixed on Cavia porcellus depilation zone and uses adhesive tape around fixing.During the administration, often use the shaver unhairing, reuse depilatory depilation in case of necessity.
4.3.7 index and the number of times observing, check, analyze and measure:
4.3.7.1 main detecting instrument: the MEK-6318K blood analyser, Japan produces.The AR of Du Pont full automatic biochemical apparatus, the U.S. produces.BECKMAN J-6B centrifuge, the U.S. produces.SAKURA automatic dehydration machine is said this product.The automatic microphotograph of OLYMPUSBH-2 system, Japan produces.
4.3.7.2 the index and the time of observation see Table 10:
Table 10
Observation index The observation content Observation time
The overview index Behavioral activity outward appearance sign feces character body weight Every day every day every day weekly
Hematological indices Leukocyte count, (WBC) lymph %, (LY%) neutral %, (GR%) the huge % that bites, (MO%) red blood cell number, (RBC) hemoglobin, (HGB) red cell volume, (HCT) mean corpuscular volume (MCV), (MCV) mean corpusular hemoglobin, (MCH) mean corpuscular hemoglobin concentration (MCHC), (MCHC) the average external volume dispersion of distribution, (RDW) platelet count, (PTL) mean platelet volume, (MPV) MPW, (PDW) clotting time D30 D40 3/5 animal 2/5 animal
Blood parameters pathological examination 1 system postmortem 2 organ coefficients ALT, (GPT/ALT) asparatate aminotransferase, (GOT/AST) paddy acyl transpeptidase, (GGT) alkaline phosphatase, (ALP) creatine kinase, (CK) blood sugar, (GLU) urea nitrogen, (BUN) total protein, (TP) albumin, (ALB) total bilirubin, (T-BIL) creatinine, (Crea) T-CHOL, (T-CHO) triglyceride, (TG) potassium, (K) sodium, (Na) chlorine, (Cl) The same
3 histological examinations Comprehensive careful gross examination of skeletal muscle heart, liver, spleen, lungs, kidney, the adrenal gland, thymus, brain, stomach, testis, epididymis, prostate (uterus, ovary) above-mentioned internal organs add pancreas again, skin, duodenum, mesenteric lymph node, thyroid The same
4.3.7.3 statistical analysis: in different sexes, group,, and carry out many group mean comparison variance branches and pray to data computation meansigma methods and standard deviations such as body weight, hematology, blood biochemical, organ organ coefficients.
4.4 result and discussion
4.4.1 animal feeding administrative situation
The Cavia porcellus that quarantine is qualified is by body weight random packet, sub-cage rearing, 5 in every cage.Be controlled at 20-24 ℃ in the experimental session room temperature, humidity is 40-70%, and animal is healthy, and disease does not meet accident.
4.4.2 general physical signs is observed:
Examine 4.4.2.1 cage is looked on: each treated animal behavioral activity is normal after giving the emplastrum that medicine of the present invention makes, no abnormal outward appearance sign.Stool colour, shape, quantity are normal.
4.4.2.2 body weight: weigh weekly once, each treated animal average weight sees Table 1,2, Fig. 1,2.Each treated animal body weight increases with age growth, compares each administration treated animal body weight no significant difference with matched group.
4.4.3 hematology and blood parameters inspection
The emplastrum that medicine of the present invention is made gives Cavia porcellus a month toxicity test continuously, and hematology's index determining the results are shown in table 3~4 behind the medicine; Clotting time sees Table 5.The serum biochemistry index determining the results are shown in table 6~9.
4.4.3.1 hematological indices changes: the result shows, administration one month, and each group (comprising matched group) hematological indices of male and female does not relatively have significant difference in range of normal value and matched group.Convalescent period, hematological indices was in normal range.Clotting time, administration one month and convalescent period, each group of administration does not more all have significant difference with matched group.
4.4.3.2 the serum biochemistry index changes: the result shows, administration one month, and the serum biochemistry index of three dosage groups and matched group be no significant difference relatively.The convalescent serum biochemical indicator belongs to normal range.
4.4.4 pathological examination:
4.4.4.1 macroscopy: there is no tangible pathological change.
4.4.4.2 organ coefficient: see Table 10~11.The result shows, administration one month and convalescent period, organ coefficient is respectively organized in administration and matched group compares no significant difference.
4.4.4.3 histological examination: the emplastrum Cavia porcellus long term toxicity test that medicine of the present invention is made, 14~15 kinds of organs and tissues specimen of the animal of sending there is no any unusual toxic reaction.See adnexa for details: laboratory animal pathology audit report.
4.5 conclusion
Continuous one month of the emplastrum percutaneous dosing that medicine of the present invention is made, each dosage group does not have the overt toxicity effect to Cavia porcellus.
The specific embodiment
Further specify characteristics of the present invention below by instantiation.
Example 1
Take by weighing Radix aconiti szechenyiani 200g, Herba speranskiae tuberculatae 50g, Radix Angelicae Dahuricae 50g, Herba Erodii 50g, Daphne giraldii Nitsche 10g, Flos Carthami 10g, Olibanum 20g, Myrrha 20g, mix, medicine is ground to form coarse powder, use 80% ethanol percolation, extracting solution simmer down to extractum.Other gets caouttchouc: 500g; Zinc oxide 100g; Colophonium: 10g; Lanoline: 50g; Vaseline: 5g; Liquid paraffin: 5g is mixed and made into substrate.The extractum of said extracted is added in the substrate, make coating, be coated with cream, cut off, the lid lining is cut into small pieces, promptly.
Example 2
Take by weighing Radix aconiti szechenyiani 200g, Herba speranskiae tuberculatae 50g, Radix Angelicae Dahuricae 50g, Herba Erodii 50g, Daphne giraldii Nitsche 10g, Flos Carthami 10g, Olibanum 20g, Myrrha 20g, mix, medicine is ground to form coarse powder, use 80% ethanol percolation, extracting solution simmer down to extractum.Other gets caouttchouc: 1000g; Zinc oxide 500g; Colophonium: 342g; Lanoline: 57g; Vaseline: 50g; Liquid paraffin: 50g is mixed and made into substrate.The extractum of said extracted is added in the substrate, make coating, be coated with cream, cut off, the lid lining is cut into small pieces, promptly.
Example 3
Take by weighing Radix aconiti szechenyiani 40g, Herba speranskiae tuberculatae 10g, Radix Angelicae Dahuricae 10g, Herba Erodii 10g, Daphne giraldii Nitsche 2g, Flos Carthami 2g, Olibanum 4g, Myrrha 4g, mix, medicine is ground to form coarse powder, use 80% ethanol percolation, extracting solution simmer down to extractum, other gets gelatin 12g, polyacrylate 6g, glycerol 25g, BASF glue 40g, tragcanth 8g mixing, add extractum again and mix, be applied on the non-woven fabrics, 25 ℃ of dryings 4 hours, coverlay, section gets final product.
Example 4
Take by weighing Radix aconiti szechenyiani 6g, Herba speranskiae tuberculatae 3g, Radix Angelicae Dahuricae 2g, Herba Erodii 50g, Daphne giraldii Nitsche 10g, Flos Carthami 10g, Olibanum 20g, Myrrha 20g, mix, medicine is ground to form coarse powder, use 80% ethanol percolation, extracting solution simmer down to extractum, other adds Tween 80 8g, liquid paraffin 12g, glycerol 12g, methyl hydroxybenzoate 0.2g mixing and emulsifying, stirring, makes ointment, and packing promptly.
Example 5
Take by weighing Radix aconiti szechenyiani 45g, Herba speranskiae tuberculatae 15g, Radix Angelicae Dahuricae 10g, Herba Erodii 15g, Daphne giraldii Nitsche 5g, Flos Carthami 5g, Olibanum 5g, Myrrha 5g mixing, medicine is ground to form coarse powder, use 80% ethanol percolation, extracting solution simmer down to extractum, add Borneolum Syntheticum 2g, wintergreen oil 2g, Semen daturae extractum 4g, Camphora 4g
Caouttchouc: 125g; Zinc oxide 20g; Colophonium: 2g; Lanoline: 10g; Vaseline: 1g; Liquid paraffin: 1g mixes, and makes coating, is coated with cream, cuts off, and the lid lining is cut into small pieces, promptly.
Example 6
Take by weighing Radix aconiti szechenyiani 45g, Herba speranskiae tuberculatae 15g, Radix Angelicae Dahuricae 10g, Herba Erodii 15g, Daphne giraldii Nitsche 5g, Flos Carthami 5g, Olibanum 5g, Myrrha 5g mixing, medicine is ground to form coarse powder, use 80% ethanol percolation, extracting solution simmer down to extractum, add Borneolum Syntheticum 2g, wintergreen oil 2g, Semen daturae extractum 4g, Camphora 4g, 1-2 propylene glycol 50ml, Arlacel-85 5g, be settled to 100ml with 40% ethanol, promptly.

Claims (8)

1, a kind of analgesic Tibetan medicine is characterized in that it being the medicament of being made by following materials based on weight:
Radix aconiti szechenyiani 20-60 part Herba speranskiae tuberculatae 5-30 part Radix Angelicae Dahuricae 5-20 part
Herba Erodii 5-30 part Daphne giraldii Nitsche 1-20 part Flos Carthami 1-10 part
Olibanum 2-15 part Myrrha 2-15 part.
2, analgesic drug product according to claim 1, wherein the weight proportion of each raw material is:
Radix aconiti szechenyiani 30-50 part Herba speranskiae tuberculatae 10-20 part Radix Angelicae Dahuricae 6-14 part
Herba Erodii 10-18 part Daphne giraldii Nitsche 3-8 part Flos Carthami 3-8 part
Olibanum 3-8 part Myrrha 3-8 part.
3, analgesic drug product according to claim 1, wherein the weight proportion of each raw material is:
10 parts of 15 parts of Radixs Angelicae Dahuricae of 45 parts of Herba speranskiae tuberculataes of Radix aconiti szechenyiani
5 parts on 5 parts of Flos Carthamis of 15 parts of Daphne giraldii Nitsche of Herba Erodii
5 parts of 5 parts of Myrrhas of Olibanum.
4,, it is characterized in that described medicament makes the dosage form of any pharmaceutics for the preparation process of pharmaceutics routinely according to claim 1,2 or 3 described pain relieving Tibetan medicines.
5,, it is characterized in that described medicament is an external preparation according to the described analgesic Tibetan medicine of claim 4.
6,, it is characterized in that described medicament is emplastrum, ointment, spray, gel or liniment according to the described analgesic Tibetan medicine of claim 4.
7, the preparation method of the described analgesic Tibetan medicine of claim 4, may further comprise the steps: (1) grinds to form coarse powder with Radix aconiti szechenyiani, Herba speranskiae tuberculatae, the Radix Angelicae Dahuricae, Herba Erodii, Daphne giraldii Nitsche, Flos Carthami, Olibanum and Myrrha medicine, use the 60-90% ethanol percolation, percolate simmer down to extractum or with 60-90% alcohol reflux 1-3 time, each 0.5-2 hour, extracting solution simmer down to extractum according to conventional method, is made said dosage form on the pharmaceutics.
8, according to the preparation method of the described analgesic Tibetan medicinal composition of claim 6, it is characterized in that Radix aconiti szechenyiani, Herba speranskiae tuberculatae, the Radix Angelicae Dahuricae, Herba Erodii, Daphne giraldii Nitsche, Flos Carthami, Olibanum and Myrrha medicine are ground to form coarse powder, use the 70-85% ethanol percolation, percolate simmer down to extractum or with 70-85% alcohol reflux 2-3 time, each 0.5-1.5 hour, extracting solution simmer down to extractum according to conventional method, is made said dosage form on the pharmaceutics.
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104523959A (en) * 2015-02-03 2015-04-22 张家界仙踪林农业科技开发有限公司 Zaocys dhumnades oil essence for massage, naprapathy and health preservation
CN105770847A (en) * 2016-05-18 2016-07-20 程敬轩 Traditional Chinese medicine composition for relieving or treating joint swelling and pain and preparation method and application of traditional Chinese medicine composition

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1433782A (en) * 2002-01-22 2003-08-06 康长生 Formula of external medicine for treating rheumatism numbness pain and preparation process thereof

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104523959A (en) * 2015-02-03 2015-04-22 张家界仙踪林农业科技开发有限公司 Zaocys dhumnades oil essence for massage, naprapathy and health preservation
CN104523959B (en) * 2015-02-03 2017-09-01 张家界仙踪林农业科技开发有限公司 A kind of health care massage zaocys dhumnades olein
CN105770847A (en) * 2016-05-18 2016-07-20 程敬轩 Traditional Chinese medicine composition for relieving or treating joint swelling and pain and preparation method and application of traditional Chinese medicine composition

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