CN1318066C - Medicine for treating dysmenorrhes and preparation thereof - Google Patents
Medicine for treating dysmenorrhes and preparation thereof Download PDFInfo
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Abstract
The present invention relates to medicine for treating women's dysmenorrhea and a preparation method thereof. The present invention is the medicine made from the following raw material of astragalus root, angelica, white peony root, hemlock parsley, ginseng, prepared rehmannia root, motherwort herb, nutgrass galingale rhizome and cinnamon. The present invention has the specific method: the nutgrass galingale rhizome and the cinnamon are immersed and distilled by water vapour to extract volatile oil; the white peony root, the motherwort herb and the prepared rehmannia root are decocted; obtained physic liquor and an aqueous solution after the volatile oil are extracted are merged, filtered, depressurized and concentrated; ethanol is added, and supernatant fluid is taken; the ethanol is recovered by depressurization to make the supernatant fluid concentrated to obtain clear paste; the astragalus root, the angelica, the hemlock parsley and the ginseng are mixed, and the ethanol is added; the astragalus root, the angelica, the hemlock parsley and the ginseng are extracted in a reflux mode; filtered liquid is depressurized to recover the ethanol and concentrated to obtain clear paste; the clear paste is merged and dried under reduced pressure to dry paste to obtain mixed powder; beta-cyclodextrin is used for completing the inclusion of the volatile oil to obtain inclusion compound powder; the inclusion compound powder is mixed with the mixed powder to obtain the medicine. The present invention has the advantages of conspicuous curative effect, safety, reliability, no toxic side effect, wide medicine source, low price, convenient oral administration and easy generalization.
Description
Technical field
The present invention relates to a kind of medicine for the treatment of dysmenorrhes, specifically is the Chinese patent medicine of feedstock production with the Chinese herbal medicine.The invention still further relates to the preparation method of this medicine.
Background technology
Dysmenorrhea is meant that the women is primary symptom in menstrual period or its front and back periodic hypogastralgia to occur, with other discomforts, so that influence work and life.Dysmenorrhea is the commonly encountered diseases and the frequently-occurring disease of gynecological clinic, and according to sampling survey in 1980, the sickness rate of China's dysmenorrhea was 33.19%, and the worker of having a strong impact on accounts for 13.59%, brings for women's physical and mental health and work and study and has a strong impact on.The medicine that is used for the treatment of dysmenorrhes at present is more, and the toxic and side effects that has is big, only cures the symptoms, not the disease, and curative effect is general; What have costs an arm and a leg.CN1234243A discloses a kind of capsule for regulating menstruation and relieving pain and preparation technology thereof, and its prescription consists of: Radix Angelicae Sinensis 9～20%, Rhizoma Chuanxiong 9～20%, the Radix Paeoniae Alba 9～20%, Radix Rehmanniae Preparata 9～20%, the Radix Aucklandiae 7～15%, Rhizoma Corydalis 7～14%, Semen Arecae 7～14%, Fructus Toosendan 7～14%.Prepared such as its adopts steam distillation, water extract-alcohol precipitation, concentrate, granulation drying and pulverizing.CN1192367A discloses a kind of Chinese medicine concentrated oral liquid and electuary for the treatment of dysmenorrhea, menoxenia, it is made into by the Radix Paeoniae Alba, the Radix Angelicae Dahuricae, Fructus Amomi, Radix Notoginseng, Rhizoma Chuanxiong, Radix Salviae Miltiorrhizae, Radix Panacis Quinquefolii, the Radix Astragali, Semen Ziziphi Spinosae, Radix Angelicae Sinensis, the Radix Polygoni Multiflori, Herba Dendrobii, Radix Polygalae, Cordyceps, Fructus Atriplicis Sibiricae, Radix Rehmanniae Preparata, the Radix Rehmanniae, Flos persicae and Poria, and its immersion decoction and concentrated packing are formed.These medicines do not obtain promoting and using in practice.
Summary of the invention
The object of the present invention is to provide a kind of evident in efficacyly, safe and reliable, have no side effect, and the medicine source is wide, price is low, and is oral easy, easily the medicine of the treatment dysmenorrhes of promoting.
Another object of the present invention provides the preparation method of the medicine of above-mentioned treatment dysmenorrhes.
For solving the problems of the technologies described above, the present invention adopts following technical scheme:
The medicine of treatment dysmenorrhes is the medicament of being made by the following weight proportion raw material: 20～60 parts of the Radixs Astragali, 20～60 parts of Radix Angelicae Sinensis, 20～60 parts of the Radix Paeoniae Albas, 20～60 parts of Rhizoma Chuanxiongs, 15～40 parts of Radix Ginsengs, 15～40 parts of Radix Rehmanniae Preparata, 15～40 parts of Herba Leonuris, 15～40 parts of Rhizoma Cyperis, 5～40 parts of Cortex Cinnamomis.
In the technique scheme, it is the medicament that preferred following weight proportion raw material is made:
40～45 parts of the Radixs Astragali, 40～45 parts of Radix Angelicae Sinensis, 30～35 parts of the Radix Paeoniae Albas, 30～35 parts of Rhizoma Chuanxiongs, 25～30 parts of Radix Ginsengs, 25～30 parts of Radix Rehmanniae Preparata, 25～30 parts of Herba Leonuris, 20～25 parts of Rhizoma Cyperis, 8～15 parts of Cortex Cinnamomis.
In the technique scheme, it can also be the medicament that preferred following weight proportion raw material is made:
42 parts of the Radixs Astragali, 42 parts of Radix Angelicae Sinensis, 33 parts of the Radix Paeoniae Albas, 33 parts of Rhizoma Chuanxiongs, 28 parts of Radix Ginsengs, 28 parts of Radix Rehmanniae Preparata, 28 parts of Herba Leonuris, 22 parts of Rhizoma Cyperis (vinegar system), 11 parts of Cortex Cinnamomis.
Preparation method of the present invention may further comprise the steps: 1. Rhizoma Cyperi, Cortex Cinnamomi are mixed by above-mentioned weight proportion and add an amount of water, soak, extract volatile oil with vapor distillation, obtained aqueous solution A is standby, and medicinal residues B is standby; 2. with the Radix Paeoniae Alba, Herba Leonuri, Radix Rehmanniae Preparata adds an amount of water by above-mentioned weight proportion and medicinal residues B mixes, decoct, water solution A behind gained medicinal liquid and the extraction volatile oil merges, filter, concentrating under reduced pressure adds ethanol and makes concentration of alcohol reach 60～70%, leave standstill, get supernatant, decompression recycling ethanol concentrates it, and C is standby for the gained clear paste; 3. the Radix Astragali, Radix Angelicae Sinensis, Rhizoma Chuanxiong, Radix Ginseng are mixed by above-mentioned weight proportion, add the ethanol of an amount of debita spissitudo, reflux, extract, filters, and decompression filtrate recycling ethanol also concentrates, and D is standby for the gained clear paste; 4. above-mentioned clear paste C and clear paste D are merged, drying under reduced pressure is pulverized to dried cream, sieves, and E is standby for the gained mixed powder; 5. the volatile oil that 1. step is collected is weighed, and finishes enclose with the beta-schardinger dextrin-of proper proportion, makes clathrate dry powder, again with the clathrate dry powder of gained and above-mentioned mixed powder E, appropriate amount of auxiliary materials mixing, the encapsulated medicament of the present invention that promptly gets of granulating.Medicament of the present invention also can be made into said other any dosage form on the pharmaceutics except that making capsule, as water preparation, pill, tablet, powder etc., all can reach identical therapeutic effect.
In above-mentioned preparation method, after mixing by above-mentioned weight proportion, the 1. middle Rhizoma Cyperi of step, Cortex Cinnamomi preferably add the water of 8～12 times of amounts; The water that preferably adds 10～15 times of amounts after the 2. middle Radix Paeoniae Alba of step, Herba Leonuri, Radix Rehmanniae Preparata mix by above-mentioned weight proportion; Step 3. in used concentration of ethanol can be 80%, its consumption is preferably the Radix Astragali, Radix Angelicae Sinensis, Rhizoma Chuanxiong, Radix Ginseng gross weight 5～12 times, the number of times of reflux, extract, is preferably 3 times, each 2 hours.The 2. middle supernatant of step is concentrated into relative density and can be 1.15～1.35, and the 3. middle filtrate of step is concentrated into relative density and can be 1.15～1.35, and described two relative density values are 60 ℃ in temperature and record.The pressure that above-mentioned steps is carried out drying under reduced pressure in 4. is preferably 0.05～0.08MPa, and temperature is 75～80 ℃, and dried cream can be crossed 80 mesh sieves after crushed.The inclusion method of above-mentioned steps in 5. is by volatile oil: beta-schardinger dextrin-is that 1: 6 weight proportion takes by weighing beta-schardinger dextrin-, beta-schardinger dextrin-is added the water heating for dissolving, make saturated solution, under stirring condition, will be with dehydrated alcohol by volatile oil: dehydrated alcohol be that the volatile oil of 1: 2 weight proportion dilution slowly adds in the beta-schardinger dextrin-saturated solution, at room temperature continues to stir 3 hours; After enclose is finished, with 4 ℃ of cold preservations of clathrate, left standstill 12～24 hours, filter, 60 ℃ of dryings are pulverized, and cross 80 mesh sieves, make clathrate dry powder.
The used Chinese crude drug of said medicine meets Chinese Pharmacopoeia one one of version in 2000 and records the kind requirement.
The Radix Astragali in the medicine of the present invention, sweet tepor is given birth to and use benefiting QI for strengthening the superficies, processs and uses invigorating the spleen and replenishing QI,＜book on Chinese herbal medicine is looked for the truth〉praise it and be: " be all medicines of QI invigorating, be so that the title of over sixty years of age to be arranged ... "" herbal classic dredge card " claims it: " soil and row three warmers in directly going into; thus can in invigorating middle warmer gas ...; field headquarters gas in the energy ...; can the descending gas of defending ... " and its QI invigorating and the effect of stimulating the menstrual flow is arranged; " herbal classic is met former " say, " Radix Astragali can all void of tonifying five ZANG-organs ... though the property temperature compensation, and can lead to blood circulation regulating, popular meridians can not hinder in heap soil or fertilizer over and around the roots stagnant yet.The Radix Astragali is then enriched blood with Radix Angelicae Sinensis with Radix Ginseng QI invigorating then ..." Radix Angelicae Sinensis, Radix Glycyrrhizae be warm in nature, benefiting blood and regulating blood circulation arranged, the effect of menstruction regulating and pain relieving." book on Chinese herbal medicine is just " praises it: " its sweet in the mouth and weighing, so specially can enrich blood, its gas is clear and hot, thus again can promoting the circulation of blood, invigorating middle warmer has, in the row benefit is arranged, the gas medicine in the sincere blood, also the panacea in the blood is also." but the two medicine benefiting QI and nourishing blood qualcomm meridian of holding concurrently is monarch.
Radix Ginseng in the described medicine, sweet little bitterness temperature has strongly invigorating primordial QI, takes off the effect of promoting the production of body fluid and inducing sedation of the mind admittedly." detailed outline " Yan Qizhi: " all deficient syndromes of male woman ", " property of medicine opinion " claims: " main the five internal organs QI-insufficiency, five kinds of strain and seven kinds of impairment is deficient thin and weak.But " promoting blood circulation of holding concurrently among this benefit of building up one's health by taking tonic." not Lu " claims it: " treat ... trusted subordinate's drum pain ... in the accent ... promoting blood circulation ...." " Xue's medical records " say: " and Radix Ginseng but go into lung meridian helps lung qi and restores menstrual flow and invigorates blood circulation, be in the gas the blood medicine also, " " must join book on Chinese herbal medicine " still say: " and Radix Ginseng, Radix Angelicae Sinensis is invigorated blood circulation.”
Radix Rehmanniae Preparata in the described medicine, sweet tepor has the merit of nourishing YIN and supplementing blood." detailed outline " claims it: " ... tonifying five ZANG-organs, internal injury deficiency, promoting blood circulation ... woman's damaging the spleen and stomach threatened abortion, uncomfortable through the marquis, tire produces all kinds of diseases and ailments." " pearl sac " claim it: " it is empty not enough to enrich blood greatly, promoting blood circulation, physical strength profiting ".
The Radix Paeoniae Alba in the described medicine, the little cold of bitter in the mouth has nourishing blood to suppress the hyperactive liver to delay the effect of middle pain relieving, and " herbal classic " claims it: " main pathogen stomachache is removed arthralgia due to stagnation of blood ... QI invigorating "." not Lu " claims it: " and clear and coherent blood vessels, slow in, dispelling malignant blood removes crafty blood ... "" property of medicine opinion " claims it: control " ... abdominal pain, vim and vigour are gathered ... strong the five internal organs, and the kidney invigorating gas is controlled ... married woman's blood closes obstructed, repercussive blood ... "" Japan hanako materia medica " claims it: " ... housewife people's one acute pain, and all diseases in antenatal back, Tong Yueshui ....”
Rhizoma Chuanxiong in the described medicine, Xin Wen.Activating QI to alleviate the depression is arranged, the effect of promoting blood circulation and stopping pain." book on Chinese herbal medicine just " says it: " its property is kind looses, and walks Liver Channel again, and the blood medicine in the gas also." " book on Chinese herbal medicine converge with speech " point out: " and the up head of rhizome of chuanxiong vault, following regulating menstruation water, middle relieving stagnation, gas medicine in the blood, by Radix Angelicae Sinensis is made, non-the invigorate blood circulation meritorious, and control gas also god test also.”
Four medicines associations monarch drug is benefiting QI and nourishing blood both, but promoting flow of QI and blood again, and invigorating middle warmer has row, the double minister that is adjusted to of QI and blood.
Rhizoma Cyperi in the described medicine, hot little hardship is sweet, and property is flat, the resolving depression of regulating the flow of vital energy, the effect of menstruction regulating and pain relieving." detailed outline " say its " ... sharp three warmers, separate six kinds of stagnation-syndromes ... married woman's bleeding not during menses, month wait uncomfortable, before the tire puerperal all kinds of diseases and ailments." Materia Medica of Decoction claims that " Rhizoma Cyperi, the gas medicine in the beneficial blood also.Controlling metrorrhagia in the side, is QI invigorating and stopping blooding also, can change blood coagulation again, be push away also old." " herbal classic dredge card " speech: " and control married woman's metrorrhagia, leukorrhagia, menoxenia person, sending down the abnormal ascending QIs all, regulating QI, due to the eliminating stagnation reason stagnates also.”
Herba Leonuri in the described medicine, arduous cool, blood circulation promoting and blood stasis dispelling is arranged, the effect of regulating menstruation." book on Chinese herbal medicine converge with speech " claims it: " ... promoting the circulation of blood is nourished blood, promoting the circulation of blood and do not hinder fresh blood, the blood stasis that do not stagnate that nourishes blood, really be blood man panacea also ... right property benefaction is walked, and can promoting the circulation of blood stimulate the menstrual flow, and repercussive is by the very victory that stagnates." two pharmacology gas clots absorbing, regulating menstruation is assistant.
Cortex Cinnamomi in the described medicine, Xin Ganre has the complement sun, warming the spleen and stomach, removing accumulated cold, the effect of promoting blood circulation." not Lu " claims speech: " main warming middle-JIAO, benefitting liver and lung gas ... promoting blood circulation ... a surname leads hundred medicines, do not have fear." " beautiful Chinese catalpa medicine is separated " speech: " Cortex Cinnamomi, the warm orderly and clearly middle wet of enriching blood greatly, fragrant sweet burying, Xin Gan goes into wood, the gas of hot perfume, benefaction stagnate and tie, and are to separate most the strongly fragrant of liver spleen ... all meridians mound stasis of bloods, hide the mansion crux, the joint obturation, diseases such as trusted subordinate's pain, wet is faint nothing but, the event of hematic cold freeze ... the woman's phase moon, puerperal, all diseases did not always go out this.”
Described medicine is with the logical property of its temperature, and a surname leads all medicines hold concurrently warming the spleen and stomach and cold relieving, and qi and blood circulation promotion and promoting blood circulation are for making.
Take a broad view of medicine of the present invention, the accent blood that nourishes blood that SIWU TANG (Radix Rehmanniae Preparata, the Radix Paeoniae Alba, Radix Angelicae Sinensis, Rhizoma Chuanxiong) is arranged, the medicine (Radix Astragali, Radix Angelicae Sinensis) that Radix Angelicae Sinensis decoction for tonifying blood is arranged, there is holy more soup (" secret record of the orchid chamber " side: Radix Ginseng, the Radix Astragali, Radix Angelicae Sinensis, Rhizoma Chuanxiong, Radix Rehmanniae Preparata, Radix Rehmanniae) to change the benefiting vital QI and blood of sanction, the effect of its benefiting QI and nourishing blood is bright, holds concurrently with logical QI and blood regulating among the right tonification.The blood-activating and qi-promoting pain relieving of foshousan (Radix Angelicae Sinensis, Rhizoma Chuanxiong) is arranged in the described medicine, the clots absorbing pain relieving of only regulating the flow of vital energy of Rhizoma Cyperi, Herba Leonuri is arranged again, and the temperature of Cortex Cinnamomi is led to menstruction regulating and pain relieving, therefore, to at the side of disease in being in fact, be adapted to the primary dysmenorrhea Chinese medical discrimination and belong to deficient qi and blood or hold the cold blood stasis under the arm the person.
Below further set forth the beneficial effect of medicine of the present invention by capsular main pharmacodynamics of the present invention and toxicological experiment (promptly treating capsular main pharmacodynamics of dysmenorrhes and toxicological experiment).
Test objective: observe capsule of the present invention to large and small Mus dysmenorrhea model, isolated rat uterus, rabbit in the body uterus, the influence of blood stasis rat blood rheological characteristic and analgesia, antiinflammatory action.
Test used material: capsule of the present invention is provided by Hebei Academy of Medical Science drug research chamber, and capsule 's content is a brown-black powder, and every 1g is equivalent to crude drug in whole 5.74g.Every capsules 0.5g places the mortar porphyrize to add water capsule 's content of the present invention during test and grinds well, and the suspension of making variable concentrations is standby.Positive control drug: TIANQI TONGJING JIAONANG, Jingxiutang (Pharmaceutical) Co., Ltd., Guangzhou produces, lot number: 01220619.YUEYUESHU CHONGJI, the Henan Province Wanxi Pharmacy Stock Co., Ltd produces, lot number: 034070.Aspirin tablet, the 25mg/ sheet, Shijiazhuang Shineway Pharmaceutical Co., Ltd produces, lot number: 20020710.FUFANG DANSHEN ZHUSHEYE, Shijiazhuang Shineway Pharmaceutical Co., Ltd produces, lot number: 20010920.Diethylstilbestrol injection, 0.5mg/ml, aminoacid company in Tianjin produces, lot number: 20000406.Oxytocin inj, 10u/ml, Nanjing new day bioid length of schooling medicine company limited, lot number: 010708.Estradiol benzoate injection, Shanghai GM pharmaceutcal corporation, Ltd produces, lot number: 009004.The adrenalin hydrochloride injection is produced lot number: 0201118 by Tianjin aminoacid company people pharmaceutical factory.
Test used instrument: desk-top self-balancing recorder, sea, Shanghai instrucment and meter plant produces.Hot plate dolorimeter RCY-2 type, instrument plant of Hebei Medical University produces.8 road physiology monitor PowerLab/8s, AD instruments.Full-automatic self-cleaning hemorheology instrument LBY-N6B, Pulisheng Instruments Co., Ltd., Beijing.
Test used animal: the SD rat, 150-250g, male, the quality certification number, the moving word the 070101st of doctor, Kunming mouse, male, the quality certification number, the moving word the 070102nd of doctor provides by Mountain Western Medicine S University's animal center.New zealand rabbit, female, the quality certification number: the moving word of doctor the: 040063, provide by Hebei province's Experimental Animal Center.
One, capsule of the present invention is to the effect of dysmenorrhea model
1, to the influence of dysmenorrhea model rat
1.92,0.96,0.48g/kg test method: select 50 of female rats for use, body weight 150-200g is divided into 5 groups at random, and model control group, positive control drug give TIANQI TONGJING JIAONANG, and (1.2g/kg), capsule of the present invention is established 3 dosage groups:.Rat back subcutaneous injection diethylstilbestrol before the experiment is injected a dosage every day and was respectively 0.8mg, 0.4mg, 0.6mg, 0.8mg totally 4 days, to improve the sensitivity of uterus to oxytocin.Began administration on the same day of injection diethylstilbestrol.After injection diethylstilbestrol and the administration in the 4th day 1 hour, every rats by intraperitoneal injection oxytocin 2u observed and causes in 30 minutes that writhing response number of times and each treated animal turn round the body suppression ratio.Then respectively organizing rat all anaesthetizes and gets blood with putting the content that the method for exempting from is measured the blood plasma beta-endorphin, with the difference of each treated animal observation index of t inspection statistics.
Result of the test: capsule 1.92,0.96 of the present invention, 0.48g/kg successive administration 4 days, the body number of times of turning round of dysmenorrhea model rat obviously reduces (P＜0.01, P＜0.05, P＜0.05), the results are shown in Table 1.
Table 1: capsule of the present invention is to the influence of dysmenorrhea rat model (X ± s)
| Group | Dosage (g/kg) | N | Turn round the body number of times | Suppression ratio (%) |
| Model control group TIANQI TONGJING JIAONANG group Capsules group of the present invention | 1.2g/kg 1.92 0.96 0.48 | 10 10 10 10 10 | 5.30±4.71 1.60±2.31 * 0.80±1.13 ** 1.20±1.87 ** 1.50±1.84 * | 10 50 60 60 50 |
Compare with model control group:
*P＜0.05,
*P＜0.01.
The test brief summary: capsule of the present invention can be alleviated the pain that the rat dysmenorrhea model causes, and dose-dependence is arranged.
2, to the influence of dysmenorrhea model mice
Test method: select 50 of female mices, 2.72,1.36,0.68g/kg body weight 20 ± 2g is divided into 5 groups at random, and model control group, positive drug give TIANQI TONGJING JIAONANG 2.0g/kg, 3 dosage groups of capsule of the present invention:, press 2mg/kg and give mouse gavaging diethylstilbestrol suspension, continuous 9 days.From the 10th day, every morning the subcutaneous injection diethylstilbestrol, gavage the capsule of the present invention of each dosage afternoon, model control group gives the normal saline with volume, the administration volume is 0.2mg/10g, for three days on end.After the last administration 30 minutes, lumbar injection oxytocin 20u/kg, writhing response number of times in the record injection back 30min is represented with X ± s, carries out statistical disposition with the t method of inspection, difference between relatively respectively organizing.
Result of the test: capsule 2.72,1.36 of the present invention, 0.68g/kg, successive administration 5 days, dysmenorrhea model mouse writhing number of times obviously reduce (P＜0.01, P＜0.001, P＜0.01); TIANQI TONGJING JIAONANG also makes the mouse writhing number of times obviously reduce (P＜0.05), the results are shown in Table 2.
Table 2: capsule of the present invention is to the influence of dysmenorrhea mouse model (X ± s)
| Group | Dosage (g/kg) | N | Turn round the body number of times |
| Model control group TIANQI TONGJING JIAONANG group Capsules group of the present invention | 1.2 2.72 1.36 0.68 | 10 10 10 10 10 | 44.33±16.64 27.10±14.03 * 25.10±14.83 ** 13.60±10.80 *** 26.30±10.76 ** |
Compare with model control group:
*P＜0.05,
*P＜0.01,
* *P＜0.001.
The test brief summary: capsule of the present invention can resist the pain that dysmenorrhea model in mice causes, shows the effect that the treatment dysmenorrhea is arranged.
Two, capsule of the present invention is to the influence in uterus
1, to the influence in isolated rat uterus
Test method: body weight 200-250g female rats, subcutaneous injection estradiol benzoate 1mg/kg, continuous 2 days.The same day was taken off neck execution with rat in experiment, cut the abdominal cavity rapidly open, peel off fatty tissue around the uterus gently, the about 1cm in clip uterus, place immediately in the Magnus' bath of the Sheng Rockwell liquid that leads to oxygen, the water bath with thermostatic control temperature remains on (37 ± 0.5) ℃, one end ligation also is fixed on the L shaped hook, the other end and tonotransducer are connected on the 8 road physiology monitors, make the uterus keep the rest tension of 1g, stablize opening entry uterine contraction curve behind the 1h, add normal saline then respectively, the positive drug YUEYUESHU CHONGJI, experiment medicine capsule of the present invention is observed the frequency (beat/10min) after the normal isolated uterine administration, intensity (g), the variation of energy (frequency * intensity).Oxytocin is caused the influence that isolated uterine shrinks: add the variation that oxytocin 50ul observes frequency, intensity, energy in the 10min after writing down one section normal contraction curve, after treating uterine contraction maximum tension and frequency stabilization, drip medicinal liquid, observe the effect of medicine antagonism oxytocin.
Result of the test: capsule 12.48mg/ml of the present invention has obvious suppression effect (P＜0.01, P＜0.01) to the normal isolated uterine contraction intensity of rat, energy, and 6.24mg/ml only has appreciable impact (P＜0.05) to energy, the results are shown in Table 3.
Capsule 12.48,6.24 of the present invention, 3.12mg/ml to oxytocin cause the isolated uterine contraction frequency, energy raises that the obvious suppression effect is all arranged; 12.48,6.24mg/ml causes the increase of isolated uterine contraction intensity to oxytocin that inhibitory action is arranged.The results are shown in Table 4.
Table 3: capsule of the present invention to the influence of isolated rat normal uterus contraction movement (X ± s, n=6)
| Group | Final concentration (mg/ml | Frequency (inferior/0min) | Intensity (g) | Energy (frequency * intensity) | |||
| Before the administration | 10min behind the medicine | Before the administration | 10min behind the medicine | Before the administration | 10min behind the medicine | ||
| YUEYUESHU CHONGJI capsule of the present invention | 25.00 12.48 6.24 3.12 | 8.62±3.72 7.14±2.59 7.14±2.59 7.14±2.59 | 5.28±0.61 4.10±3.33 5.71±1.96 5.76±2.12 | 7.09±0.68 8.23±1.56 8.23±1.56 8.23±1.56 | 4.80±0.22 *** 3.23±2.23 ** 6.32±1.95 7.97±1.70 | 60.90±26.71 58.18±21.11 58.18±21.11 58.18±21.11 | 25.37±2.91 ** 15.54±13.41 ** 34.01±7.10 * 43.97±10.04 |
With comparison before the administration,
*: P＜0.05,
*: P＜0.01,
* *: P＜0.001.
Table 4: capsule of the present invention causes the influence (X ± s) of isolated rat uteri excitation effect to oxytocin
| Group | Animal (only) | Final concentration mg/ml | Intensity (g) | Frequency (inferior/10 minute) | Energy (frequency * intensity) | Suppression ratio (%) |
| The oxytocin of normal control group contracts+and the YUEYUESHU group contracts+the present invention contracts+and the present invention contracts+the present invention | 8 8 8 8 8 8 | 0.005u/ml 20.00 12.48 6.24 3.12 | 5.83 ±0.75 8.17±1.00 △△△5.89±1.09 **1.15±0.88 ***5.46±1.26 ***7.44±1.21 | 1.83±0.88 9.11±0.56 △△△ 5.31±1.32 ** 1.66±1.77 *** 6.23±1.16 *** 7.16±1.35 ** | 10.92±5.67 74.52±10.25 △△△ 31.36±9.68 *** 3.14±5.03 *** 34.65±10.62 *** 52.88±11.79 ** | 52.27±2.91 95.91±6.22 54.64±10.32 29.01±13.07 |
Compare with the normal control group
△ △ △: P＜0.001; With give after the oxytocin relatively
*P＜0.01,
* *P＜0.001.
The test brief summary: capsule of the present invention has inhibitory action to contraction frequency, amplitude, the energy of the normal isolated uterine of rat, and can resist the contraction potentiation in the isolated rat uterus that oxytocin causes.Direct anti-oxytocin effect has been described, can have removed the spasm of uterine smooth muscle, the treatment dysmenorrhea.
2, to the influence of rabbit in the body uterus
Test method:
(1) operating procedure: get 30 of Female rabbits, be divided into 5 groups at random, 6 every group, be divided into blank group, positive drug group (TIANQI TONGJING JIAONANG, 2.0g/kg) and 3 dosage groups of capsule of the present invention: 2.25,0.75,0.25g/kg.Tested preceding two days, every rabbit intramuscular injection every day diethylstilbestrol injection 0.5mg/kg is to improve the sensitivity of uterus muscle to oxytocin.During experiment, water 12h is can't help in the rabbit fasting, with amobarbital sodium 80mg/kg intraperitoneal injection of anesthesia, faces upward the position and is fixed in operating-table, and the abdominal part cropping in xiphoid-process lower edge ventrimeson otch, is found out duodenum, inserts conduit, and purse string suture is fixing.Locate to do the 4-5cm median incision again on pubic symphysis, separating uterus is used in the body uterus method of dangling and connects dull and stereotyped monitor record uterine activity (uterus rest tension 1g) by tonotransducer.After stablizing 30 minutes, opening entry uterine activity curve.
(2) medication: duodenal administration, give capsule of the present invention, TIANQI TONGJING JIAONANG and isopyknic normal saline (10ml/kg) respectively, per 10 minutes frequency of uterine contraction (beat/10min) of opening entry, amplitude (mm, baseline is to the distance of maximum crest), energy (frequency * amplitude) behind the administration 30min.Behind the administration 1h, every rabbit intramuscular injection oxytocin 5u behind the 5min, writes down the uterotonic frequency of every 10min, amplitude and energy.
Result of the test: after giving capsule 2.25,0.75 of the present invention, 0.25g/kg, with before the administration relatively, make significantly slow down at body normal uterus contraction frequency (P＜0.001, P＜0.001, P＜0.05); 0.25,0.75g/kg makes energy reduce significantly (P＜0.001, P＜0.01); And make the normal uterus shrinkage amplitude obviously reduce (P＜0.05, P＜0.05).The results are shown in Table 5.
Energy after capsule 2.25 of the present invention, the 0.75g/kg administration, frequency, amplitude significantly reduce with matched group, and can obviously weaken rabbit that oxytocin causes at body uterine contraction potentiation, with matched group significant difference are arranged relatively.The results are shown in Table 6.
Table 5: capsule of the present invention to rabbit the influence of body normal uterus contraction movement (X ± s, n=6)
| Group | Dosage (g/kg) | Frequency (inferior/10min) | Amplitude (mm) | Energy (frequency * amplitude) | |||
| Before the administration | 30min behind the medicine | Before the administration | 30min behind the medicine | Before the administration | 30min behind the medicine | ||
| Matched group TIANQI TONGJING JIAONANG capsule of the present invention | Deng capacity 2.0 2.25 0.75 0.25 | 11.16±2.71 12.16±3.97 11.33±1.63 12.16±5.49 11.83±3.31 | 11.16±2.40 △△* 5.16±2.04 △△* 6.33±2.33 △* 7.66±1.75 9.00±2.75 | 23.33±7.71 22.00±6.72 22.16±5.52 21.00±4.09 23.16±8.93 | 24.83±7.41 25.00±8.89 △* 13.50±7.50 △* 15.83±3.18 18.66±9.83 | 257.83±110.55 271.50±137.10 248.16±59.66 259.50±133.35 280.00±148.82 | 258.33±94.87 132.50±85.43 △△△** 81.16±70.50 △△* 104.66±24.60 165.66±89.45 |
With comparison before the administration,
△: P＜0.05,
△ △: P＜0.01,
△ △ △: P＜0.001; Compare with matched group,
*: P＜0.05,
*: P＜0.01.
Table 6: capsule of the present invention to oxytocin cause rabbit the influence of body uteri excitation effect (X ± s, n=6)
| Group | Dosage (g/kg) | Frequency (inferior/minute) | Amplitude (mm) | Energy (frequency * amplitude) | ||||||
| Normally | 30min behind the medicine | Behind the Oxy | Normally | 30min behind the medicine | Behind the Oxy | Normally | 30min behind the medicine | Behind the Oxy | ||
| Matched group TIANQI TONGJING JIAONANG capsule of the present invention | Deng capacity 2.0 2.25 0.75 0.68 | 11.16 ±2.71 12.16 ±3.97 11.33 ±1.63 12.16 ±5.94 11.83 ±3.31 | 10.66 ±2.87 5.16 ** ±2.04 6.33 ** ±2.33 6.66 * ±1.21 9.00 ±2.75 | 12.33 ±3.82 9.16 ±3.31 9.50 ±3.61 10.33 ±4.84 13.16 ±2.92 | 23.33 ±7.71 22.00 ±6.72 22.16 ±5.52 21.00 ±4.09 23.16 ±8.93 | 24.83 ±7.41 25.00 ±8.89 13.50 *±7.50 15.83 *±3.18 18.66 ±9.83 | 37.33 ±11.00 25.83 ±10.64 16.83 ±8.13 18.16 ±4.49 28.83 ±16.65 | 257.83 ±110.55 271.50 ±137.10 248.16 ±59.66 259.50 ±133.35 280.00 ±48.82 | 258.33 ±94.87 132.50 ±85.42 81.16 ±70.50 104.66 ±24.60 165.66 ±89.45 | 493.16 ±288.01 244.66 *±118.92 160.66 **±85.79 195.33 **±132.07 393.00 ±294.54 |
Compare with matched group,
*: P＜0.05,
*: P＜0.01.Oxy: oxytocin.
The test brief summary: capsule of the present invention is similar in the influence of body uterus and isolated uterine to rabbit, not only can reduce normal contraction frequency, amplitude and energy in the body uterus, and the uterine contraction that oxytocin causes is strengthened having inhibitory action.Show that further this medicine has the reduction activity intensity to uterine smooth muscle, alleviate the spasm effect.
Three, capsular analgesic activity of the present invention
1, the influence of Dichlorodiphenyl Acetate induced mice pain reaction
Test method: select 50 of the healthy Kunming mouses of body weight 18-22g for use, male and female half and half, 2.72,1.36,0.68g/kg be divided into 5 groups at random, model control group, positive drug are selected TIANQI TONGJING JIAONANG (2.0g/kg), 3 dosage groups of capsule of the present invention for use:, each organizes equal gastric infusion, continuous 5 days, the administration volume is 20ml/kg, and 1h after the last administration, ip0.6% acetum 0.2ml/ are only, observed and recorded is respectively organized in the mice 30min clock and is turned round the body number of times, respectively organizes difference.
Result of the test: capsule 2.72,1.36 of the present invention, 0.68g/kg successive administration 5 days, that can obviously reduce mice pain model that acetic acid causes turns round body number of times (the P value all＜0.05).The results are shown in Table 7.
Table 7: the influence of capsule Dichlorodiphenyl Acetate induced mice pain model of the present invention (X ± s)
| Group | Dosage (g/kg) | N | Turn round the body number of times |
| Model control group TIANQI TONGJING JIAONANG group Capsules group of the present invention | 2.0 2.72 1.36 0.68 | 10 10 10 10 10 | 25.70±7.87 13.90±9.99 ** 15.50±9.94 * 16.20±10.27 * 19.40±14.25 |
Compare with model control group:
*P＜0.05,
*P＜0.01.
2, capsule of the present invention is to the influence of hot plate induced mice pain
Test method: regulate water bath with thermostatic control: earlier with the water bath topped up with water, make water surface contact hot plate, regulate thermostat and make water temperature be controlled at 55 ± 0.5 ℃, hot plate needs preheating 10 minutes.Room temperature: 20 ℃.
Get 18-22g female mice number, each 1 is placed on the hot plate, and mice is from being placed on the hot plate to the pain threshold of metapedes required time (second) as this Mus occurring licking.Allly lick the metapedes time less than 5 seconds or give it up greater than 30 seconds or leaper.Repeat to survey its normal pain threshold before the administration, get threshold of pain meansigma methods twice, as pain threshold before this Mus administration.
2.72,1.36,0.68g/kg observe drug effect, the blank group is established in experiment, irritates the stomach distilled water, and positive drug is selected TIANQI TONGJING JIAONANG 2.0g/kg for use, and experiment medicine capsule of the present invention is established 3 dosage groups:.Each organizes equal gastric infusion 5 days, and the administration volume is 20ml/kg, measures after each mice administration 30,60,90,120 minutes pain threshold on the 5th day.Still reactionless as 60 seconds, mice is taken out, in order to avoid scald, calculated with 60 seconds its threshold of pain.
Result of the test: capsule 2.72g/kg of the present invention and Radix Notoginseng group, after administration 90 minutes with administration before relatively, pain threshold obviously improves; Capsule 1.36 of the present invention, 0.68g/kg 120 minutes pain thresholds after administration obviously improve (the P value all＜0.05).The results are shown in Table 8.
Table 8: capsule of the present invention causes the influence (X ± s) of mice pain to hot plate method
| Group | Dosage (g/kg) | N | Pain threshold (s) before the administration | Pain threshold after the administration (s) | |||
| 30min | 60min | 90min | 120min | ||||
| Model group TIANQI TONGJING JIAONANG capsule of the present invention | 2.0 2.72 1.36 0.68 | 10 10 10 10 10 | 16.15±7.77 17.45±4.87 14.30±7.95 15.75±6.96 14.20±4.86 | 14.40±8.47 25.70±13.15 * 16.15±7.72 19.30±12.60 14.50±5.53 | 19.01±8.07 29.50±14.63 18.60±7.50 26.40±13.94 20.15±15.00 | 17.15±9.87 30.50±15.62 * 30.90±17.29 * 29.40±15.76 20.60±14.77 | 16.10±10.78 28.60±14.41 * 34.80±17.54 * 31.70±16.15 * 30.20±17.08 * |
Compare with model control group:
*P＜0.05,
*P＜0.01,
* *P＜0.001.
The test brief summary: capsule of the present invention can obviously improve the mice pain threshold that acetic acid and hot plate method cause, shows that capsule of the present invention has analgesic activity.
Four, capsular antiinflammatory action of the present invention
1, the influence of the mice ear that causes of xylol
Test method: select 50 of healthy Kunming mouses for use, male and female half and half, be divided into 5 groups at random, model control group, positive drug group (aspirin 0.2g/kg), 3 dosage groups of capsule of the present invention 2.72,1.36,0.68g/kg, each organizes equal gastric infusion, continuous 6 days, the administration volume was 0.2ml/10g.30min after the last administration drips dimethylbenzene in mouse right ear, and 15min puts to death animal, along left and right sides auricle same area punching, the both sides auricle is weighed respectively with the 6mm card punch, with two auricle weight differences as the swelling level index, obtain suppression ratio, respectively organize difference.
Result of the test: capsule 2.72,1.36 of the present invention, 0.68g/kg successive administration 6 days, the mice ear that xylol causes have obvious suppression effect (P＜0.01, P＜0.05, P＜0.05), the results are shown in Table 9.
Table 9: the influence of capsule xylol induced mice auricle edema of the present invention (X ± s)
| Group | Dosage (g/kg) | N | Swelling degree (mg) | Suppression ratio (%) |
| Model group aspirin capsule of the present invention | 0.2 2.72 1.36 0.68 | 10 10 10 10 10 | 3.40±1.25 1.20±1.40 ** 1.20±1.14 ** 2.00±1.05 * 2.00±1.05 * | 64.73 64.73 41.18 41.18 |
Compare with model control group:
*P＜0.05,
*P＜0.01.
2, intersection dish glue is caused the influence of rat toes swelling
Test method: get 50 of healthy SD rats, male, body weight 200 ± 20g is divided into 5 groups at random, 1.92,0.96, O.15g/kg 0.48g/kg, positive control drug give aspirin 3 dosage groups of capsule of the present invention:, the blank group gives the distilled water of same volume.Each organizes equal gastric infusion 5 days, after administration in last 1 day 1 hour, O.1ml/ only intersect dish glue in the subcutaneous injection 1% of the right back toes of rat, cause scorching back and measured toes thickness in 1,2,4,6 hour respectively, be calculated as follows the swelling rate, compare the difference between each time point administration group and blank group respectively, represent, respectively organize difference with the t inspection statistics with X ± s.
Result of the test: capsule 1.92,0.96 of the present invention, 0.48g/kg cause the swelling of rat toes and are causing scorching back 4 hours and begin to occur inhibitory action (P value all＜0.05) intersecting dish glue, act on the most obvious (P＜0.01, P＜0.05, P＜O.01) in 6 hours.Aspirin begins to occur inhibitory action causing scorching back 2 hours, and experimental result sees Table 10.
Table 10: capsule of the present invention causes the influence of rat paw edema to intersection dish glue
| Group | Dosage (g/kg) | Number of animals (only) | Cause scorching back different time swelling rate (%) | |||
| 1h | 2h | 4h | 6h | |||
| Blank group aspirin group capsule of the present invention | 0.15 1.92 0.96 0.48 | 10 10 10 10 10 | 39.06±9.42 35.29±10.10 44.284±9.72 40.46±13.54 41.39±6.06 | 61.11±20.28 40.97±13.79 * 49.24±10.82 48.75±18.35 48.52±9.67 | 70.69±26.06 42.46±21.08 * 47.68±11.41 * 50.40±14.12 * 51.55±8.08 * | 68.33±23.87 38.24±15.42 ** 43.37±12.17 ** 45.05±15.52 * 40.84±8.96 ** |
Compare with the blank group:
*P＜O.05,
*P＜0.01.
The test brief summary: the mice ear that capsule xylol of the present invention causes and the dish glue that intersects cause the swelling of rat toes all the obvious suppression effect, shows that this medicine has antiinflammatory action.
Five, capsule of the present invention is to the influence of blood stasis rat blood rheological characteristic
Test method: get 60 of Healthy female rats, body weight 200 ± 20g is divided into 6 groups at random, and 10 every group, the blank group is given and wait capacity distilled water 10ml/kg, continuous 7 days every day.Blood stasis model group distilled water every day is irritated stomach 1Oml/kg, continuous 7 days, modeling in the 8th day.1.92,0.96,0.48g/kg positive control drug is selected liquid salvia for use, and (4g (crude drug)/kg) gastric infusion, once a day, continuous 7 days, capsule of the present invention was established 3 dosage groups:, press the 10ml/kg body weight every day and irritate stomach, continuous 7 days.Give normal saline in the 8th day blank matched group, other respectively organizes equal subcutaneous injection adrenalin hydrochloride (8 μ g/kg) 2 times, midfeather 2 hours, after the administration 2 hours for the first time, animal is put 5min in the frozen water, dispose back 24 hours, anaesthetize with 20% urethane, abdominal aortic blood, wherein 1.5ml blood injects rapidly in the anticoagulant heparin pipe, shakes up the back and measures hemorheology index; 1.2ml blood blood capillary centrifugal determination erythrocyte sedimentation rate value and packed cell volume value.Each testing index value is represented with X ± s, respectively organizes the difference of each index.
Result of the test: the high, medium and low whole blood viscosity of cutting of model group rat all forms than matched group rising explanation blood stasis model.Capsule 1.92,0.96 of the present invention, 0.48g/kg rise to the whole blood viscosity that the rat blood stasis model causes, and high, medium and low cutting all has the reduction effect; Capsule 0.96g/kg of the present invention also all has the reduction effect to high, medium and low the cutting of whole blood reduced viscosity index, and can obviously reduce the erythrocyte rigidity index.FUFANG DANSHEN ZHUSHEYE also has above-mentioned similar effect, the results are shown in Table 11.
Table 11: capsule of the present invention is to the hemorheological influence of Blood stasis rat
| Project | Matched group | Model group | The positive drug group | High dose group | Middle dosage group | Low dose group |
| Number of animals dosage (g/kg) is low to be cut and cuts (m.Pa) height in (m.Pa) and cut low the cutting of (m.Pa) capillary plasma viscosity packed cell volume (%) reduction and cut (m.Pa) reduction height in (m.Pa) reduction and cut (m.Pa) erythrocyte aggregation index Rigidity of red cells index deformable index erythrocyte electrophoresis index | 10 - 12.10±1.87 6.76±0.75 5.24±0.42 5.24±0.42 49.65±2.24 21.97±3.14 11.29±1.25 8.22±0.65 2.29±0.21 7.18±0.82 0.91±0.43 4.63±0.28 | 11 - 14.39±1.97# 7.68±0.87# 5.86±0.52# 1.15±0.01 51.95±1.96 24.83±2.84 12.31±1.35 8.92±0.85 2.43±0.16 7.79±0.96 0.92±0.05 4.67±0.22 | 9 4.00 11.59±1.94 ** 6.33±0.86 ** 4.87±0.53 ** 1.30±0.10 49.04±1.89 20.93±3.80 10.28±0.80 * 7.29±1.13 ** 2.37±0.18 5.69±1.10 ** 0.90±0.02 4.84±0.39 | 9 1.92 11.70±2.16 * 6.75±0.94 * 5.28±0.60 * 1.30±0.14 46.15±2.58 22.42±3.88 11.78±1.88 8.62±1.29 2.21±0.22 6.76±1.42 0.93±0.08 4.77±0.29 | 8 0.96 10.82±1.75 ** 6.17±0.59 ** 4.82±0.40 ** 1.32±0.31 48.06±1.90 19.84±3.85 * 10.12±1.50 * 9.80±0.71 2.24±0.20 5.83±1.54 ** 0.78±0.24 4.66±0.43 | 8 0.48 11.78±1.43 * 6.25±0.49 ** 5.07±0.40 ** 1.08±0.20 47.50±2.88 22.39±3.76 10.74±0.95 8.27±0.74 2.32±0.17 7.28±0.96 0.95±0.03 4.90±0.42 |
Compare with matched group: #P＜0.05, compare with model control group:
*P＜0.05,
*P＜0.01.
The test brief summary: capsule of the present invention can make the blood stasis model whole blood viscosity descend, and illustrates that this medical instrument has blood circulation promoting and blood stasis dispelling, dredge the meridian passage effect.
Capsular toxicological experiment of the present invention
1, acute toxicity test
In one day, irritate stomach at twice for mice by 40g/kg/d dosage after, observe and see the toxic reaction generation in 14 days.Capsular maximum dosage-feeding of the present invention is equivalent to 533 times of clinical consumption greater than 40g/kg.
2,90 days long term toxicity tests
Capsule medicated powder suspension of the present invention is pressed high dose (50.51g crude drug/kg respectively, 80 times of quite clinical consumptions), middle dosage (25.26g crude drug/kg, 40 times of quite clinical consumptions), low dosage (12.63g crude drug/kg, 20 times of quite clinical consumptions) give rat oral gavage, once a day, continuous 90 days.The result shows, successive administration is after 90 days, the general situation of animal, body weight gain no abnormality seen; Hematological indices no abnormality seens such as the hemoglobin of each administration group (HGB), red blood cell count(RBC) (RBC), platelet count (PLT), numeration of leukocyte (WBC) and classification; Aspartic acid aminotransferase (AST), ALT (ALT), alkali phosphatase (ALP), blood urea nitrogen (BUN), total protein (TP), albumin (ALB), blood glucose (GLU), total bilirubin (T-BIL), creatinine (Grea), T-CHOL blood biochemicals such as (T-CHO) are learned index, with the relatively more equal no significant difference (P＞0.05) of blank group; The main organs weight coefficient of each administration treated animal is all normal; Pathological examination shows that each rat testicle seminiferous tubule lumen diameter of high dose group increases, and each layer spermatogenic epithelium cell number increases, and increases obviously with spermatogonium, primary spermatocyte number especially.Interstitial cell number between each seminiferous tubule increases.All the other are respectively organized each internal organs and show no obvious abnormalities.It is all normal that the general situation of drug withdrawal rat after 14 days, hematological indices, blood biochemical are learned index.The organ weights coefficient is all normal.Histopathologic examination, the high dose group rat testis changes and alleviates to some extent, and all the other are respectively organized each internal organs and there is no unusually.
Conclusion (of pressure testing) and discussion:
1, capsule 1.92,0.96 of the present invention, 0.48g/kg have the obvious suppression effect to the body number of times of turning round of rat dysmenorrhea model, 2.72,1.36,0.68g/kg has the obvious suppression effect to the body number of times of turning round of dysmenorrhea model in mice, points out this medicine that the convulsive dysmenorrhea in uterus is had therapeutical effect.
2, capsule 1.92mg/ml of the present invention to the normal isolated uterine contraction intensity of rat, energy with administration before relatively, the obvious suppression effect is arranged, 0.96mg/ml only has remarkable inhibitory action to energy.
Capsule 12.48,6.24 of the present invention, 3.12mg/ml to oxytocin cause the isolated uterine contraction frequency, energy raises that the obvious suppression effect is all arranged.12.48,6.24mg/ml causes the increase of isolated uterine contraction intensity to oxytocin that inhibitory action is arranged.The inhibitory action that capsule of the present invention causes isolated uterine contraction frequency, amplitude, energy to oxytocin is better than the effect to normal isolated uterine.
3, capsule 2.25,0.75 of the present invention, 0.25g/kg be to rabbit apparent in view reduction before body normal uterus energy is with administration, and make the uterine activity frequency deceleration; Capsule 12.62g/kg of the present invention also makes shrinkage amplitude obviously reduce.
Can resist rabbit that oxytocin causes after capsule 2.25 of the present invention, the 0.75g/kg administration at body uterine contraction potentiation, motion frequency, amplitude, energy are obviously reduced.Show that capsule of the present invention all has inhibitory action to normal and pathological state uterine smooth muscle, prompting can be alleviated the violent contraction of uterine smooth muscle and play the effect for the treatment of dysmenorrhea.
4, capsule 2.72,1.36 of the present invention, 0.68g/kg can obviously improve hot plate and cause mice pain threshold in the pain reaction, and obviously reduce mice pain model that acetic acid causes turn round the body number of times.Show that capsule of the present invention has analgesic activity.
5, the mice ear that causes of capsule 2.72,1.36 of the present invention, 0.68g/kg xylol has the obvious suppression effect; 1.92,0.96,0.48g/kg causes the swelling of rat toes and begins to occur inhibitory action causing scorching back 4 hours intersecting dish glue, effect in 6 hours is the most obvious.Show that capsule of the present invention has antiinflammatory action.Can help TREATMENT OF DYSMENORRHOEA by improving chronic inflammatory disease.
6, capsule 1.92,0.96 of the present invention, 0.48g/kg all have the reduction effect to high, medium and low the cutting of whole blood viscosity rising that the rat blood stasis model causes; Capsule 0.96g/kg of the present invention also all has the reduction effect to high, medium and low the cutting of whole blood reduced viscosity, and obviously reduces the erythrocyte rigidity index.Illustrate that capsule of the present invention has function of promoting blood circulation to disperse blood clots, point out this medicine to adjust QI and blood and lose freely, and play the effect for the treatment of dysmenorrhea by blood circulation promoting and blood stasis dispelling.
7, the long term toxicity test result according to acute toxicity and 90 days thinks that capsule of the present invention is taken safe and reliable under prescribed dose.
Above-mentioned test main reference document:
Chief editors such as Xu Shuyun: pharmacological experimental methodology, second edition, People's Health Publisher 1991:1467; Qi Chen chief editor: herbal pharmacology experimental methodology, People's Health Publisher 1996; Sun Haiyan etc., the foundation of dysmenorrhea model in mice, Chinese Pharmacological circular, 2002,18 (2): 233-6; Liu Zhaoyang, warm palace relaxation grain is to the influence of blood stasis hemorheology of rat, Chinese patent medicine, 2000,22 (5): 36; Zhang Jinmei etc., few abdomen remove the capsular main pharmacodynamics research of the stasis of blood, new Chinese medicine and clinical pharmacology, 1976,7 (4): 30-32; Medicine management department of Ministry of Health of the People's Republic of China, study of tcm new drug guide (pharmacy, pharmacology, toxicology), 94-0198:164; Zhou Liguo, drug toxicology, Hubei science tech publishing house, 2001:20-58; Yuan Baijun, Wang Zhiqiao, safety evaluatio and practice before new drug is clinical, military medicine Science Press, 1997:23-61.
In sum, medicine of the present invention has lax uterine smooth muscle, blood circulation promoting and blood stasis dispelling, spasmolytic antiinflammatory and analgesic activity.Simultaneously, medicine of the present invention is done therapeutic test to 100 dysmenorrhea patients, and that obtains significant curative effect accounts for 68%, substantially effectively account for 29%, invalid accounts for 3%, and total effective rate reaches 97%, it is evident in efficacy, and it is big to have overcome some poisonous side effect of medicine, the drawback of only curing the symptoms, not the disease; By to 100 dysmenorrhea patients clinical observation, find poison, side reaction, application is described, and it is safe and reliable, has no side effect; And medicine of the present invention source is wide, and price is low, and is oral easy, promotes easily.
The specific embodiment
Embodiment one
1, prescription: the Radix Astragali 420 grams, Radix Angelicae Sinensis 420 grams, the Radix Paeoniae Alba 330 grams, Rhizoma Chuanxiong 330 grams, Radix Ginseng 280 grams, Radix Rehmanniae Preparata 280 grams, Herba Leonuri 280 grams, Rhizoma Cyperi (vinegar system) 220 grams, Cortex Cinnamomi 110 grams.
2, preparation method: it may further comprise the steps: 1. Rhizoma Cyperi (vinegar system), Cortex Cinnamomi are mixed (8～12 times of amounts that add by above-mentioned weight proportion, as 10 times of amounts) 3300 water that restrain, soak 10～15 hours (such as 12 hours), extracted 8 hours with steam distillation, collect volatile oil, obtained aqueous solution A is standby, and medicinal residues B is standby; 2. with the Radix Paeoniae Alba, Herba Leonuri, Radix Rehmanniae Preparata adds (10～15 times of amounts by above-mentioned weight proportion, such as 12 times of amounts) 10680 the gram water and medicinal residues B mix, decoct 3 times, each 1 hour, water solution A behind gained medicinal liquid and the extraction volatile oil merges, filter, (60 ℃ record to be evaporated to relative density and to be 1.0～1.3, such as relative density is 1.15), add 95% ethanol and make determining alcohol reach 70%, left standstill 10～24 hours, get supernatant, decompression recycling ethanol and to be concentrated into relative density be 1.15～1.35 (60 ℃ record, and are 1.30 such as relative density), C is standby for the gained clear paste; 3. the Radix Astragali, Radix Angelicae Sinensis, Rhizoma Chuanxiong, Radix Ginseng are mixed by above-mentioned weight proportion, add (5～12 times of amounts, such as 8 times of amounts) concentration be about 11600 grams of 80% ethanol, reflux, extract, 3 times, each 2 hours, filter decompression filtrate recycling ethanol and to be concentrated into relative density be that 1.15～1.35 (60 ℃ record, such as relative density is 1.30), D is standby for the gained clear paste; 4. above-mentioned clear paste C and clear paste D being merged, is 0.05～0.08MPa (such as 0.06MPa) at pressure, and temperature is that drying under reduced pressure is pulverized to dried cream under 75～80 ℃ (such as 80 ℃), crosses 80 mesh sieves, and gained mixed powder E 444 grams are standby; 5. the volatile oil that 1. step is collected is weighed, and (volatile oil weighs 1.7 grams, its yield is generally 0.2～0.6%), beta-schardinger dextrin-with proper proportion is finished enclose, its inclusion method is by volatile oil: beta-schardinger dextrin-is that 1: 6 weight proportion takes by weighing beta-schardinger dextrin-(β-CD) 10.2 restrain, beta-schardinger dextrin-is added the water heating for dissolving, make saturated solution, under stirring condition, to slowly add in the beta-schardinger dextrin-saturated solution with the volatile oil that 3.4 gram dehydrated alcohol (by volatile oil: dehydrated alcohol is 1: 2 a weight proportion) dilute, at room temperature continue to stir 3 hours, after enclose is finished, with 4 ℃ of cold preservations of clathrate, left standstill 24 hours, filter, 60 ℃ of dryings are pulverized, cross 80 mesh sieves, clathrate dry powder 11.6 grams and above-mentioned mixed powder E of gained, adjuvant (as starch) 44.4 gram mixings, the encapsulated medicament that promptly gets of granulating, 1 gram medicament is equivalent to crude drug in whole 5.74 grams.Present embodiment makes 1000 of hard capsules, every heavy 0.5 gram.
3, usage and consumption: oral, one time 2～4, three times on the one.
Embodiment two
1, prescription: the Radix Astragali 4000 grams, Radix Angelicae Sinensis 4000 grams, the Radix Paeoniae Alba 3000 grams, Rhizoma Chuanxiong 3000 grams, Radix Ginseng 2500 grams, Radix Rehmanniae Preparata 2500 grams, Herba Leonuri 2500 grams, Rhizoma Cyperi 2000 grams, Cortex Cinnamomi 800 grams.
2, preparation method: it may further comprise the steps: Rhizoma Cyperi, Cortex Cinnamomi are mixed the water that adds 15 times of amounts by above-mentioned weight proportion, soaked 20 hours, and extracted volatile oil 5～10 hours (as 9 hours), collect volatile oil with steam distillation, obtained aqueous solution A is standby, and medicinal residues B is standby; 2. the Radix Paeoniae Alba, Herba Leonuri, Radix Rehmanniae Preparata are mixed by water and the medicinal residues B that above-mentioned weight proportion adds 17 times of amounts, decoct 2～4 times, each 1～1.5 hour, water solution A behind gained medicinal liquid and the extraction volatile oil merges, filter, being evaporated to relative density is 0.9 (60 ℃ record), adding 90～95% ethanol makes determining alcohol (content) reach 60%, left standstill 10～24 hours, get supernatant, (can at 60 ℃) decompression recycling ethanol and to be concentrated into relative density be 1.40 (60 ℃ record), C is standby for the gained clear paste; 3. the Radix Astragali, Radix Angelicae Sinensis, Rhizoma Chuanxiong, Radix Ginseng are mixed by above-mentioned weight proportion, the concentration that adds 13 times of amounts is 70～90% ethanol, reflux, extract, 2～3 times, each 1.5～2.5 hours, merge extractive liquid,, filter, filtrate (can at 60 ℃) decompression recycling ethanol and to be concentrated into relative density be 1.10 (60 ℃ record), D is standby for the gained clear paste; 4. above-mentioned clear paste C and clear paste D being merged, is 0.05MPa at pressure, and temperature is extremely dried cream of 80 ℃ of following drying under reduced pressure, pulverizes, and crosses 80 mesh sieves, and E is standby for the gained mixed powder; 5. the volatile oil that 1. step is collected is weighed, beta-schardinger dextrin-with proper proportion is finished enclose, its inclusion method is by volatile oil: beta-schardinger dextrin-is that 1: 6 weight proportion takes by weighing beta-schardinger dextrin-(β-CD), beta-schardinger dextrin-is added the water heating for dissolving, make saturated solution, under stirring condition, will be with dehydrated alcohol by volatile oil: dehydrated alcohol be that the volatile oil of 1: 2 weight proportion dilution slowly adds in the beta-schardinger dextrin-saturated solution, at room temperature continue to stir 2～3 hours, after enclose is finished, with 4 ℃ of cold preservations of clathrate, left standstill 12～24 hours, and filtered 60 ℃ of dryings, pulverize, cross 80 mesh sieves, the clathrate dry powder of gained and above-mentioned mixed powder E, appropriate amount of auxiliary materials (as magnesium stearate) mixing, the encapsulated medicament that promptly gets of granulating.Medicament of the present invention also can be made into said other any dosage form on the pharmaceutics except that making capsule, as water preparation, pill, tablet, powder etc.
3, usage and consumption are with embodiment one.
Embodiment three
1, prescription: the Radix Astragali 4500 grams, Radix Angelicae Sinensis 4500 grams, the Radix Paeoniae Alba 3500 grams, Rhizoma Chuanxiong 3500 grams, Radix Ginseng 3000 grams, Radix Rehmanniae Preparata 3000 grams, Herba Leonuri 3000 grams, Rhizoma Cyperi 2500 grams, Cortex Cinnamomi 1500 grams.
2, preparation method is with embodiment one or embodiment two.
3, usage and consumption are with embodiment one.
Embodiment four
1, prescription: the Radix Astragali 2000 grams, Radix Angelicae Sinensis 2000 grams, the Radix Paeoniae Alba 2000 grams, Rhizoma Chuanxiong 2000 grams, Radix Ginseng 1500 grams, Radix Rehmanniae Preparata 1500 grams, Herba Leonuri 1500 grams, Rhizoma Cyperi 1500 grams, Cortex Cinnamomi 500 grams.
2, preparation method is with embodiment one or embodiment two.
3, usage and consumption are with embodiment one.
Embodiment five
1, prescription: the Radix Astragali 6000 grams, Radix Angelicae Sinensis 6000 grams, the Radix Paeoniae Alba 6000 grams, Rhizoma Chuanxiong 6000 grams, Radix Ginseng 4000 grams, Radix Rehmanniae Preparata 4000 grams, Herba Leonuri 4000 grams, Rhizoma Cyperi 4000 grams, Cortex Cinnamomi 4000 grams.
2, preparation method is with embodiment one or embodiment two.
3, usage and consumption are with embodiment one.
Embodiment six
1, prescription: the Radix Astragali 4000 grams, Radix Angelicae Sinensis 4500 grams, the Radix Paeoniae Alba 3200 grams, Rhizoma Chuanxiong 3500 grams, Radix Ginseng 2800 grams, Radix Rehmanniae Preparata 3000 grams, Herba Leonuri 2600 grams, Rhizoma Cyperi 2300 grams, Cortex Cinnamomi 1000 grams.
2, preparation method is with embodiment one or embodiment two.
3, usage and consumption are with embodiment one.
Embodiment seven
1, prescription: the Radix Astragali 5500 grams, Radix Angelicae Sinensis 3800 grams, the Radix Paeoniae Alba 6000 grams, Rhizoma Chuanxiong 2500 grams, Radix Ginseng 2000 grams, Radix Rehmanniae Preparata 3000 grams, Herba Leonuri 3500 grams, Rhizoma Cyperi 2900 grams, Cortex Cinnamomi 3600 grams.
2, preparation method is with embodiment one or embodiment two.
3, usage and consumption are with embodiment one.
Claims (10)
1, a kind of medicine for the treatment of dysmenorrhes is characterized in that it is the medicament of being made by the following weight proportion raw material:
20～60 parts of the Radixs Astragali, 20～60 parts of Radix Angelicae Sinensis, 20～60 parts of the Radix Paeoniae Albas, 20～60 parts of Rhizoma Chuanxiongs, 15～40 parts of Radix Ginsengs, 15～40 parts of Radix Rehmanniae Preparata, 15～40 parts of Herba Leonuris, 15～40 parts of Rhizoma Cyperis, 5～40 parts of Cortex Cinnamomis.
2, the medicine of treatment dysmenorrhes according to claim 1 is characterized in that it is the medicament of being made by the following weight proportion raw material:
40～45 parts of the Radixs Astragali, 40～45 parts of Radix Angelicae Sinensis, 30～35 parts of the Radix Paeoniae Albas, 30～35 parts of Rhizoma Chuanxiongs, 25～30 parts of Radix Ginsengs, 25～30 parts of Radix Rehmanniae Preparata, 25～30 parts of Herba Leonuris, 20～25 parts of Rhizoma Cyperis, 8～15 parts of Cortex Cinnamomis.
3, the medicine of treatment dysmenorrhes according to claim 1 is characterized in that it is the medicament of being made by the following weight proportion raw material:
42 parts of the Radixs Astragali, 42 parts of Radix Angelicae Sinensis, 33 parts of the Radix Paeoniae Albas, 33 parts of Rhizoma Chuanxiongs, 28 parts of Radix Ginsengs, 28 parts of Radix Rehmanniae Preparata, 28 parts of Herba Leonuris, 22 parts of Rhizoma Cyperi (processed with vinegar), 11 parts of Cortex Cinnamomis.
4,, it is characterized in that said medicament is a said dosage form on any pharmaceutics according to the medicine of claim 1 or 2 or 3 described treatment dysmenorrhes.
5, the medicine of treatment dysmenorrhes according to claim 4 is characterized in that said medicament is a capsule.
6, the preparation method of the medicine of the described treatment dysmenorrhes of a kind of claim 5 is characterized in that it may further comprise the steps:
1. Rhizoma Cyperi, Cortex Cinnamomi are mixed by above-mentioned weight proportion and add an amount of water, soak, extract volatile oil with vapor distillation, (A) is standby for obtained aqueous solution, and (B) is standby for medicinal residues;
2. with the Radix Paeoniae Alba, Herba Leonuri, Radix Rehmanniae Preparata adds an amount of water by above-mentioned weight proportion and medicinal residues (B) mix, decoct, aqueous solution (A) behind gained medicinal liquid and the extraction volatile oil merges, filter, concentrating under reduced pressure adds ethanol and makes concentration of alcohol reach 60～70%, leave standstill, get supernatant, decompression recycling ethanol concentrates it, and (C) is standby for the gained clear paste;
3. the Radix Astragali, Radix Angelicae Sinensis, Rhizoma Chuanxiong, Radix Ginseng are mixed by above-mentioned weight proportion, add the ethanol of an amount of debita spissitudo, reflux, extract, filters, and decompression filtrate recycling ethanol also concentrates, and (D) is standby for the gained clear paste;
4. above-mentioned clear paste (C) and clear paste (D) are merged, drying under reduced pressure is pulverized to dried cream, sieves, and (E) is standby for the gained mixed powder;
5. the volatile oil that 1. step is collected is weighed, and finishes enclose with the beta-schardinger dextrin-of proper proportion, makes clathrate dry powder, again with the clathrate dry powder of gained and above-mentioned mixed powder (E), appropriate amount of auxiliary materials mixing, the encapsulated medicament that promptly gets of granulating.
7, the preparation method of the medicine of treatment dysmenorrhes according to claim 6 is characterized in that adding after Rhizoma Cyperi, Cortex Cinnamomi mixed by above-mentioned weight proportion during above-mentioned steps 1. the water of 8～12 times of amounts; The water that adds 10～15 times of amounts after the 2. middle Radix Paeoniae Alba of step, Herba Leonuri, Radix Rehmanniae Preparata mix by above-mentioned weight proportion; Step 3. in used concentration of ethanol be 80%, its consumption is the Radix Astragali, Radix Angelicae Sinensis, Rhizoma Chuanxiong, Radix Ginseng gross weight 5～12 times, the number of times of reflux, extract, is 3 times, each 2 hours.
8, the preparation method of the medicine of treatment dysmenorrhes according to claim 6, it is characterized in that it is 1.15～1.35 that the 2. middle supernatant of above-mentioned steps is concentrated into relative density, it is 1.15～1.35 that the 3. middle filtrate of step is concentrated into relative density, and described two relative density values are 60 ℃ in temperature and record.
9, the preparation method of the medicine of treatment dysmenorrhes according to claim 6, the pressure that it is characterized in that carrying out during above-mentioned steps is 4. drying under reduced pressure is 0.05～0.08MPa, and temperature is 75～80 ℃, and dried cream is crossed 80 mesh sieves after crushed.
10, the preparation method of the medicine of treatment dysmenorrhes according to claim 6, it is characterized in that the inclusion method during above-mentioned steps 5. is by volatile oil: beta-schardinger dextrin-is that 1: 6 weight proportion takes by weighing beta-schardinger dextrin-, beta-schardinger dextrin-is added the water heating for dissolving, make saturated solution, under stirring condition, will be with dehydrated alcohol by volatile oil: dehydrated alcohol be that the volatile oil of 1: 2 weight proportion dilution slowly adds in the beta-schardinger dextrin-saturated solution, at room temperature continues to stir 3 hours; After enclose is finished, with 4 ℃ of cold preservations of clathrate, left standstill 12～24 hours, filter, 60 ℃ of dryings are pulverized, and cross 80 mesh sieves, make clathrate dry powder.
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| CN1318066C true CN1318066C (en) | 2007-05-30 |
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| CN100393319C (en) * | 2005-11-08 | 2008-06-11 | 南京工业大学 | Astragaloside cyclodextrin clathrate, its prepn. and preparing mehtod |
| CN101940609B (en) * | 2010-07-19 | 2012-06-06 | 李君� | Medicinal liquor for treating dysmenorrhea |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1123178A (en) * | 1995-06-05 | 1996-05-29 | 中国人民解放军南京军区南京总医院 | Formula of traditional Chinese medicine for curing endometriosis and preparation and preparation technology thereof |
| CN1192367A (en) * | 1998-04-17 | 1998-09-09 | 陈昀海 | Concentrated traditional Chinese medicinal oral liquor or granule for treating dysmenorrhea and irregular menstruation |
| CN1457848A (en) * | 2003-06-11 | 2003-11-26 | 天津中新药业集团股份有限公司乐仁堂制药厂 | Black-bone chicken white phoenix preparation medicine and its preparing method |
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2005
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1123178A (en) * | 1995-06-05 | 1996-05-29 | 中国人民解放军南京军区南京总医院 | Formula of traditional Chinese medicine for curing endometriosis and preparation and preparation technology thereof |
| CN1192367A (en) * | 1998-04-17 | 1998-09-09 | 陈昀海 | Concentrated traditional Chinese medicinal oral liquor or granule for treating dysmenorrhea and irregular menstruation |
| CN1457848A (en) * | 2003-06-11 | 2003-11-26 | 天津中新药业集团股份有限公司乐仁堂制药厂 | Black-bone chicken white phoenix preparation medicine and its preparing method |
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| 复方消经痛胶囊质量标准研究 李存满，中成药，第26卷第8期 2004 * |
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