CN101049367A - Preparation of Chinese medicament for treating hemicrania - Google Patents
Preparation of Chinese medicament for treating hemicrania Download PDFInfo
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Abstract
A Chinese medicine in the form of pill, powder, particle, tablet, syrup, capsule, or mixture for treating hemicrania is prepared from 11 Chinese-medicinal materials including Chuan-xiong rhizome, scorpion, centipede, white peony root, etc.
Description
One, technical field.
The present invention relates to the migrainous compound Chinese medicinal preparation of a kind of treatment, belong to field of medicaments.
Two, background technology.
Migraine is the vascular headache of the repeated relapsing due to nerve-dysfunction of blood vessel.Have the people more than 10% to suffer from this disease in western countries, and Most patients is the women; At the migrainous sickness rate of China is 4.2%～14.6%, M-F 1: 4.Modern medicine thinks that its definite pathogenesis is unclear, but with neural, dysfunction of blood vessel is relevant.The outbreak initial stage have earlier intracranial vessel spasm, regional blood flow change, cause and follow the nervous system premonitory symptom accordingly, the outer vasodilation of secondary cranium, vaso-active substance and algogenic substance Kallidin I ooze out, and are deposited on around the blood vessel, cause the persistence headache.The traditional Chinese medical science thinks that migraine is mainly because of due to imbalance of liver spleen renal function and wind-fire phlegm stagnation in collateral, and blood circulation promoting and blood stasis dispelling, suppressing the hyperactive liver and subsiding YANG, dispelling pathogenic wind and eliminating phlegm are treatment three rule of treatment.There is the author to add up 51 treatment vascular headache prescriptions, finds the medicine that dispels the wind, insect medicine, promoting blood circulation to remove obstruction in the collateral medicine etc. are generally paid attention to.Thought wind medicine can reach on the top, mountain peak, with the medicine treatment primary disease 62.7% that dispels the wind; Insect medicine can be searched wind and dispel the wind, the spasmolytic pain relieving, drug for invigorating blood circulation and eliminating stasis scalable antiotasis is improved blood viscosity, Rhizoma Chuanxiong is a gas medicine in the blood, use at most, account for 70.8%.
At present, domestic Western medicine triptan, the Ergotamine almost used, A, P, C cobratoxin, must to manage analgesic such as pain, dipyrone, flunarizine be the main treatment migraine, triptan can cause that peripheral vessels shrinks ischemia, can not prevent outbreak and expense costliness, limits its application.The pain relieving Western medicine can only alleviating pain, can't effect a radical cure, and side effect is big.
The invention provides a kind of determined curative effect, safe ready, little, the cheap pure traditional Chinese compound medicine of side effect.
Three, summary of the invention.
The invention provides the migrainous Chinese medicine preparation of a kind of treatment, said preparation by Cornu Saigae Tataricae, Rhizoma Chuanxiong, Scorpio, Scolopendra, the Radix Paeoniae Alba, Bombyx Batryticatus, the Radix Angelicae Dahuricae, Ramulus Uncariae Cum Uncis, Radix Notoginseng, Radix Rehmanniae, Radix Glycyrrhizae Preparata ten simply Chinese medicine form.
Chinese medicine preparation of the present invention has the effect of suppressing the hyperactive liver to relieve the wind syndrome and network pain relieving.Be used for wind-yang and up-boring, channels disharmony type migraine, disease is seen head distending pain or jumping pain, see with frontal temporal part pain more, or dizzy or susceptible to lose temper due to restlessness, uneasy sleeping at night, dry mouth with bitter taste, red tongue or purple dark, yellow fur, stringy pulse or stringy and thready pulse number.
Chinese medicine preparation of the present invention, during its prescription was formed: Cornu Saigae Tataricae is salty-cold, return liver, heart channel, suppressing the hyperactive liver to relieve the wind syndrome, Rhizoma Chuanxiong blood-activating and qi-promoting, wind-expelling pain-stopping was monarch drug; Scorpio, Scolopendra, the Radix Paeoniae Alba, Bombyx Batryticatus, the Radix Angelicae Dahuricae, Ramulus Uncariae Cum Uncis, Radix Rehmanniae endogenous wind stopping relieving convulsion, removing obstruction in the collateral to relieve pain, auxiliary Cornu Saigae Tataricae suppressing the hyperactive liver to relieve the wind syndrome act as ministerial drug; Radix Notoginseng hemostasis dissipating blood stasis sedative action is an adjuvant drug, is equipped with the Radix Glycyrrhizae relieving spasm to stop pain, and coordinating the actions of various ingredients in a prescription is a messenger drug.And the anxious pain of contraction in the peony and licorice decoction treatment abdomen, evident in efficacy.
Chinese medicine preparation of the present invention, during its prescription is formed:
2 parts～9 parts of 12 parts～50 parts Scolopendras of 12 parts～50 portions Scorpios of 12 parts～50 parts Rhizoma Chuanxiongs of Cornu Saigae Tataricae
15 parts～60 parts of 12 parts～50 parts Ramulus Uncariae Cum Uncis of 15 parts～60 parts Radixs Angelicae Dahuricae of 30 parts～120 parts Bombyx Batryticatus of the Radix Paeoniae Alba
5 parts～20 parts of 15 parts～60 parts Radix Glycyrrhizae Preparata of 6 parts～24 portions Radix Rehmanniae of Radix Notoginseng
Preferably:
3 parts～6 parts of 19 parts～33 parts Scolopendras of 19 parts～33 portions Scorpios of 19 parts～33 parts Rhizoma Chuanxiongs of Cornu Saigae Tataricae
23 parts～39 parts of 19 parts～33 parts Ramulus Uncariae Cum Uncis of 23 parts～39 parts Radixs Angelicae Dahuricae of 46 parts～78 parts Bombyx Batryticatus of the Radix Paeoniae Alba
7 parts～13 parts of 23 parts～39 parts Radix Glycyrrhizae Preparata of 9 parts～16 portions Radix Rehmanniae of Radix Notoginseng
More preferably:
4.5 parts of 25 parts of Scolopendras of 25 portions of Scorpios of 25 parts of Rhizoma Chuanxiongs of Cornu Saigae Tataricae
30 parts of 25 parts of Ramulus Uncariae Cum Uncis of 30 parts of Radixs Angelicae Dahuricae of 60 parts of Bombyx Batryticatus of the Radix Paeoniae Alba
10 parts of 30 parts of Radix Glycyrrhizae Preparata of 12 portions of Radix Rehmanniae of Radix Notoginseng
In more than forming, each component is to calculate with the crude drug percentage by weight, if be unit with the gram, this composition can be made into 1000 doses of pharmaceutical preparatioies, the final drug preparation that described 1000 doses of fingers are made, as be 1000 of capsule preparations, 1000 in tablet, 1000 bags of granules, 1000 bottles of oral liquids etc.
In more than forming, as if being unit with part, can be made into the preparation of 50～1000 taking doses, as capsule, make 1000, each taking dose can be 1～20, can take altogether 50～1000 times.
More than form to be by weight as proportioning, when producing, can increase or reduce according to corresponding proportion, as large-scale production can be unit with the kilogram, or be unit with the ton, small-scale production can be a unit with gram or milligram also, weight can increase or reduce, but the constant rate of the raw medicinal herbs weight proportion between each composition.
The ratio of above weight proportion obtains through science screening, and for especial patient, the proportioning of can corresponding adjustment forming increases or reduce being no more than 100%.
Chinese medicine preparation of the present invention, can add the medicine acceptable carrier when being prepared into medicament, described medicine acceptable carrier can be: starch, sucrose, lactose, dextrin, mannitol, inorganic salts, cellulose and derivant thereof, silicon derivative, alginic acid and its esters, gelatin, polyvidone, glycerol, Tweens, agar, surfactant, Polyethylene Glycol, cyclodextrin, beta-schardinger dextrin-, phospholipid, Pulvis Talci, magnesium stearate, sulfated lauryl alcohol class etc.
Chinese medicine preparation of the present invention can be any pharmaceutically useful dosage form, and these dosage forms comprise: pill, powder, granule, tablet, lozenge, soft extract, colloid, syrup, cataplasma, mixture, drop pill, capsule, medicated wine, tincture, extractum, plaster, rubber-emplastrum, ointment, distillate medicinal water, medicinal tea, injection, liniment, suppository, nasal drop, eye drop, aerosol, spray.Preparation of the present invention, peroral dosage form preferably, as: pill, powder, granule, tablet, lozenge, soft extract, syrup, mixture, capsule, medicated wine, tincture, extractum etc., preferably capsule.
Preparation of the present invention is determined usage and dosage according to patient's situation in use, but obeys every day three times, each 1～20 dose, and as 1～20 or sheet.
Chinese medicine preparation of the present invention prepares by the following method:
More than ten simply, get Cornu Saigae Tataricae, Scorpio, Scolopendra, Bombyx Batryticatus, the Radix Notoginseng five tastes, sterilization, oven dry is ground into fine powder, mixing.Get the Radix Paeoniae Alba, the Radix Angelicae Dahuricae, Radix Rehmanniae, Radix Glycyrrhizae Preparata four flavors, decoct with water secondary, each 1 hour.Filter, merging filtrate, being concentrated into relative density is the clear paste of 1.15～1.20 (90～95 ℃).Get Rhizoma Chuanxiong, Ramulus Uncariae Cum Uncis two flavors,, add 8 times of amounts at every turn and extracted 2 hours with 80% ethanol extraction secondary.Filter, merging filtrate, filtrate is concentrated into the clear paste that relative density is 1.15～1.20 (90～95 ℃).Merge above-mentioned two kinds of clear paste, stir evenly, add above-mentioned fine powder, mixing is prepared into preparation with the ordinary preparation manufacturing technology.As make capsule, and the medicine of above-mentioned mixing can be added appropriate amount of starch, mixing is granulated, and drying incapsulates, and makes 1000, promptly.
Below by main pharmacodynamics research, toxicological test and clinical trial beneficial effect of the present invention is described.
Below the used medicine of test is the medicine according to the method preparation of the embodiment of the invention 1, called after antelope rhizome of chuanxiong capsule.
(1) main pharmacodynamics research
1, medicine
Antelope rhizome of chuanxiong capsule face with preceding with mortar with its abundant porphyrize, use the dissolving of 1% sodium carboxymethyl cellulose liquid or Krebs ' liquid to be made into the solution (pH6.4～6.8) of desired concn then.
2, animal:
Animal for research provides by Department of Health of Guangdong Province medical experimental animal field.White mice, NIH kind (quality certification number 93022); Rabbit, New Zealand kind (quality certification number 93023); Equal healthy unpregnancy.Fasting 12h before the experiment, but give 5% sugar-salt-water from drink.
3, date processing:
Experimental data is represented with " mean ± standard deviation ".Group difference significance test measurement data is checked the enumeration data X 2 test with variance analysis or t.
4, method and result:
4.1 influence to the central nervous system
4.1.1 influence to normal spontaneous activity in mice: 50 of NIH mices, body weight 20.5 ± 1.0g, ♀ ♂ has both, and is divided into matched group, stable 20mg/kg group, antelope rhizome of chuanxiong capsule 550mg/kg group and 2750mg/kg group.Except that stable group only the 7th day gastric infusion 1 time, each organizes gastric infusion 1 time every day; The administration volume is 20ml/kg.Matched group gives to irritate stomach with 1% sodium carboxymethyl cellulose liquid of medicine group equal-volume (20ml/kg).Continuous 7 days.After administration in the 7th day 1 hour, with mice place with the many plate count boxes that link to each other with instrument of YSD-4 type pharmacology physiology in, allow its adaptation 1min earlier.Then, spontaneous activity number in the continuous record mice 5min.The results are shown in Table 1.
Table 1: each organizes the spontaneous activity in mice number relatively
| Group | Number of animals (only) | Spontaneous activity number of times (inferior/5 minute) |
| The stable 20mg/kg group of matched group 1%cmc sodium liquid 20mg/kg antelope rhizome of chuanxiong capsule 550mg/kg group antelope rhizome of chuanxiong capsule 2750mg/kg group | 14 12 12 12 | 76±18 73±27 50±24** 57±19* |
* P＜0.05, * * P＜0.01, with matched group relatively.As seen, the spontaneous activity in mice number of antelope rhizome of chuanxiong capsule 2750mg/kg group and stable group obviously reduces.Show that antelope rhizome of chuanxiong capsule has certain sedation.
4.1.2 to pentobarbital sodium in mice sleep function influence: 50 of NIH mices, body weight 21.0 ± 1.2g, ♀ ♂ has both.The same method grouping, administration.After administration in the 7th day 1 hour, each organized lumbar injection pentobarbital sodium 50mg/kg body weight, the induction period and the length of one's sleep of record mice sleep.The results are shown in Table 2.
Table 2: each group is to the influence of pentobarbital sodium in mice sleep effect.
| Group | Number of animals (only) | The sleep derivation phase (minute) | The length of one's sleep (minute) |
| The stable 20mg/kg group of matched group 1%cmc sodium liquid 20mg/kg antelope rhizome of chuanxiong capsule 550mg/kg group antelope rhizome of chuanxiong capsule 2750mg/kg group | 14 12 12 12 | 4.0±0.4 4.4±1.2 4.5±1.6 2.4±0.5** | 24.9±8.9 36.3±10.5* 39.8±9.4** 111.7±14.2** |
* P＜0.05, * * P＜0.01 and matched group comparison.The result shows: stable can obviously shorten the induction period of pentobarbital sodium in mice sleep and prolong its length of one's sleep, though and antelope rhizome of chuanxiong capsule does not have influence to its induction period, can obviously prolong its length of one's sleep.Show that antelope rhizome of chuanxiong capsule can strengthen the inhibitory action of central nervous depressant to the central nervous system.
4.2 analgesic activity
4.2.1 Dichlorodiphenyl Acetate causes the influence of mouse writhing reaction: 50 of NIH mices, body weight 20.4 ± 1.1g, ♀ ♂ has both, and is divided into matched group, acetaminophen 294mg/kg group, antelope rhizome of chuanxiong capsule 550mg/kg group and 2750mg/kg group.Every day gastric infusion once, continuous 7 days.After one hour, lumbar injection 0.6% acetum 0.2ml/ only brought out the mouse writhing reaction in administration in the 7th day.The number of times of writhing response takes place in record to mice in the 15min behind the acetum.The results are shown in Table 3.
Table 3: each organizes the influence that Dichlorodiphenyl Acetate causes the mouse writhing reaction
| Group | Number of animals (only) | Spontaneous activity number of times (inferior/15 minute) |
| Matched group 1%cmc sodium liquid 20mg/kg antelope rhizome of chuanxiong capsule 550mg/kg group antelope rhizome of chuanxiong capsule 2750mg/kg group acetaminophen 294mg/kg group | 14 12 12 12 | 27±5 16±4** 12±6** 7±2** |
Compare with matched group * P＜0.01.The result shows: antelope rhizome of chuanxiong capsule can obviously reduce mice twisting number of times with acetaminophen is the same, shows significant analgesia role.
4.2.2 thermostimulation is caused the influence of mice pain reaction: 50 of female NIH mice, body weight 20.6 ± 1.3g is divided into 1% sodium carboxymethyl cellulose matched group, Pethidine 30mg/kg group, antelope rhizome of chuanxiong capsule 165,550,1650mg/kg group.Except that the Pethidine group was the lumbar injection administration, each group was all to irritate the stomach administration 1 time.The administration volume is the 20ml/kg body weight.Before administration, mice is placed on 55 ℃ of hot plates, survey the mice pain response time (dropping on the hot plate time that metapedes or jump appear licking in mice) from mice, behind the 5min, resurvey 1 time.With 2 times averages is the mice basis pain response time before the administration.Select the basis pain response time 10-30 mice in second, give relative medicine.Respectively at after the administration 15,30,60,90min measures the mice pain response time.The results are shown in Table 4.
Table 4: each group causes the influence that mice reacts bitterly to thermostimulation
| Group | The basis pain response time (second) | The pain response time (second) after the administration | |||
| 15min | 30min | 60min | 90min | ||
| Control group antelope rhizome of chuanxiong capsule 165mg/kg group antelope rhizome of chuanxiong capsule 550mg/kg group antelope rhizome of chuanxiong capsule 1650mg/kg group pethidine 30mg/kg group | 13.2±3.9 13.5±3.1 14.5±2.7 13.1±1.6 12.7±3.2 | 12.3±5.0* 19.2±8.7* 20.4±8.7** 24.1±7.2** 25.8±7.8 | 16.7±4.7* 23.2±6.2* 24.7±9.6** 29.4±8.6** 26.7±7.6 | 18.2±4.2** 25.4±5.4** 29.8±9.9** 33.3±9.2* 25.9±7.5 | 18.3±7.5* 27.4±7.4** 32.6±9.6** 35.5±9.3* 25.6±6.5 |
* P＜0.05, * * P＜0.01, n is 10.Show as seen thus, antelope rhizome of chuanxiong capsule can obviously prolong the mice pain reaction time with Pethidine is the same, and has tangible dose-effect relationship, shows significant analgesia role.
4.3 the Medulla Leporis seu Oryctolagi circulation is influenced
New zealand rabbit, 20, ♂, body weight 1.73 ± 0.20kg is divided into 1% sodium carboxymethyl cellulose matched group, Buddhist nun flat 10mg/kg group, antelope rhizome of chuanxiong capsule 465mg/kg group and 1550mg/kg group not.Ear vein injection pentobarbital sodium 30mg/kg anesthesia.It is fixing to face upward the position.The cervical region median incision is made tracheal intubation, and intubate one end links to each other with respiration energy converting device (TR-612T), through coupling amplifier (AR-650H, AA-601H) recording respiration (R).Separate down and ligation both sides vertebral artery in neck root clavicle.One side femoral arteriography, and link to each other with the TP-200T pressure transducer, through pressure amplifier (AP-641T) record mean arterial blood pressure (MBP).Trigger Cardiotacs (AT-601G) recorded heart rate (HR) with arterial pulse wave.Separate bilateral carotid, its external carotid artery of ligation and branch thereof, the FB hook electromagnetic flowmeter that hangs up bore (1mm) in bilateral carotid is respectively popped one's head in, and connects MFV-1200 type electromagnetic blood flowmeter (Japanese photoelectricity), measures both sides ICAF amount.Both sides internal carotid artery flow sum is represented full cerebral blood flow (CBF).With MBP/CBF is cerebral vascular resistance (CVP).These parameters is recorded on the four road physiology monitors (RM-6000 type, Japanese photoelectricity) simultaneously.Postoperative is stablized 30min.After treating that each observation index is stable, through duodenal lumen administration 1 time (the administration volume is 10ml/kg), observation 120min.The variation of comparative control group and each observation index of administration group.Experiment is got full brain and is weighed after finishing.
4.3.1 effect to CBF: antelope rhizome of chuanxiong capsule 465mg/kg and 1550mg/kg all after administration 30min make CBF begin obvious increase, increase to 60min CBF and to reach maximum, increment rate is respectively 58 ± 10% and 70 ± 12%, effect continues to 75min and 120min after the administration respectively, is obvious dose dependent.Not flat of Buddhist nun 30min after the administration begins CBF is obviously increased, and has increased by 41 ± 12% to 60min CBF, and effect continues to 90min after the administration.
4.3.2 effect to CVR: antelope rhizome of chuanxiong capsule 465mg/kg and 1550mg/kg all after administration 30min make CVR begin obvious minimizing, reduce to 60min CVR and to reach maximum, slip is respectively 35 ± 9% and 46 ± 9%, effect continues to 75min and 120min after the administration respectively, also is obvious dose dependent.Not flat of Buddhist nun also makes CVR obviously reduce, and effect 30min after the administration begins to continue to 120min after the administration always.
4.3.3 the effect to MBP, HR, R: antelope rhizome of chuanxiong capsule does not all have obvious influence (P＞0.05) to MBP, HR, R.Not flat of Buddhist nun then makes MBP and HR obviously descend, effect respectively after the administration 45min and 30min begin to continue to 120min after the administration, but frequency and the amplitude of R are not all had influence.
4.4 influence to isolated rabbit basilar artery ring (BAR) contractile response
New Zealand rabbit, ♂, body weight 2.0-2.5kg.The front portion of tapping the head causes dizzyly, takes out full brain rapidly and puts in 4 ℃ of oxygen-saturated Krebs ' liquid.Isolate basilar artery, cut and make the long vascular ring specimen of 4mm, hang in the stripped bath that fills 5ml Krebs ' liquid (PH7.3-7.4, continues logical 95%O2+5%CO2 gas by 37.5 ± 0.2 ℃).Contractile response is traced on the two autobalance instrument of XWT-264 through the tension transducer conversion.Tranquillization load 500mg, 2 hours every 20min of equilibration time change liquid 1 time.It is 20% concentration that antelope rhizome of chuanxiong capsule was joined with Krebs ' liquid dissolving before administration in 2-4 hour, gets supernatant and tests.Norepinephrine (NE) is the Mingxing Pharmaceutical Factory, Guangzhou ampulla, and KCI is Beijing chemical reagent factory product, and 5-hydroxy tryptamine (5-HT) is the Sigma product, all is made into desired concn in facing the time spent with Krebs ' liquid.
4.4.1 the BAR rest tension is influenced:
(1) amount-result relation: BAR adds to 16mg/ml by 2 times of concentration that increase progressively from antelope rhizome of chuanxiong capsule 0.5mg/ml and manufactures the accumulation amount effect curve of antelope rhizome of chuanxiong capsule to the influence of BAR rest tension behind above-mentioned equilibrium process.The result obtains: antelope rhizome of chuanxiong capsule can cause that BAR shrinks, and along with the increase of antelope rhizome of chuanxiong capsule concentration, the contractile response of BAR increases, and is obvious dose dependent.Antelope rhizome of chuanxiong capsule causes that the concentration of BAR maximal contractile response is 16mg/ml, causes that the concentration that the BAR contractile response reaches 50% maximal contractile response is that ED50 is 2.33 ± 0.76mg/ml.
In addition, also observe in the experiment, the ability that the antelope rhizome of chuanxiong capsule medicinal liquid of preparing above 10 hours before the administration brings out the BAR contraction obviously weakens; Surpass 24 hours makers-ups, do not have this effect substantially.
(2) time-effect relationship: bring out BAR with antelope rhizome of chuanxiong capsule 1mg/ml, 3mg/ml and 16mg/ml respectively and shrink Continuous Observation 15min.The result obtains: each concentration of antelope rhizome of chuanxiong capsule all after administration 3min cause that BAR produces maximal contractile response.As the maximal contractile response that brings out with antelope rhizome of chuanxiong capsule 16mg/ml is 100% increment rate, and then 3mg/ml and 1mg/ml bring out 59 ± 3% and 27 ± 3% contractile response increment rate respectively.Thereafter, contractile response descends gradually, and to 15min, contractile response drops to 65 ± 6%, 18 ± 15% and 0 ± 11% respectively.Show dose is big, causes that the BAR contractile response is big, and contractility is held time length, decline slowly.
(3) with the contraction of vasoconstrictor KCI, 5-HT, NE relatively: on same BAR, make KCI, NE, 5-HT respectively, antelope rhizome of chuanxiong capsule brings out the accumulation amount effect curve that BAR shrinks.Calculate the pD2 of each medicine, relatively the usefulness of each medicine.The result is as follows: antelope rhizome of chuanxiong capsule causes that the pD2 of BAR contractile response is 2.56 ± 0.14 (log g/ml); KCI, NE, 5-HT cause that the pD2 of BAR contractile response is respectively 1.56 ± 0.05,5.79 ± 0.07,7.81 ± 0.26 (log mol/L).The usefulness of each medicine is maximum with KCI, the NE minimum, antelope rhizome of chuanxiong capsule is between 5-HT and NE, and the usefulness comparing difference of capsular usefulness of antelope rhizome of chuanxiong and KCI has significance meaning (P＜0.05), but does not have significance meaning (P＞0.05) with the usefulness comparing difference of NE, 5-HT.
4.4.2 KCI, NE, 5-HT are brought out the influence of BAR contractile response: on different B AR, manufacture the accumulation amount effect curve that KCI, NE, 5-HT bring out the BAR contractile response respectively.15min adds antelope rhizome of chuanxiong capsule 1mg/ml or 3mg/ml before repeating to manufacture KCI, NE, 5-HT accumulation dose-effect allusion quotation line, and observation is to the variation of each amount effect curve behind the antelope rhizome of chuanxiong capsule.As seen, the amount effect curve that antelope rhizome of chuanxiong capsule can make KCI, NE, 5-HT shrink BAR moves to right, and ceiling effect forces down, and moves to right and the degree and the antelope rhizome of chuanxiong capsule dosage that force down are proportionate, and shows as the non-antagonism of striving property unexpectedly.The PD of its antagonism KCI, NE, 5-HT
2' be respectively 2.68 ± 0.16,2.45 ± 0.28,2.13 ± 0.25 (logmol/l).Two compare, all difference remarkable (P＜0.05).Show that the anti-KCI effect of antelope rhizome of chuanxiong capsule is stronger, a little less than the anti-5-HT effect.
4.5 K in the 20% antelope rhizome of chuanxiong capsule medicinal liquid supernatant
+, Ca
2+Determination on content
With two steaming glass distilled water unit distilled water antelope rhizome of chuanxiong capsule is made into 20% concentration, left standstill 1 hour, get supernatant, after 2500 commentaries on classics/min, 10min are centrifugal, on HITACHI180-70 ZAAS atomic absorption spectrophotometer, measure total K
+, Ca
2+Content.The result is: K
+1610mg/L, Ca
2+754mg/L.Also be K
+41.18mmol/L, Ca
2+18.81mmol/L.
Obtaining the ED50 that antelope rhizome of chuanxiong capsule causes the BAR contractile response in the stripped BAR experiment in front is 2.33mg/ml, is that 20% antelope rhizome of chuanxiong capsule liquid 0.058ml adds the concentration in the 4.5ml solution.Like this, the K that raises by antelope rhizome of chuanxiong capsule
+Concentration is 0.0188mg/ml (being got by 0.058ml * 1.61mg/ml ÷ 5ml), also is the K of 0.48mmol/L of having raise in the body lotion
+Add K in former Krebs ' liquid
+Content 6mmol/L, total K
+Concentration is 6.48mmol/L, far below K
+Bring out the ED of BAR contractile response
112.83 ± 1.9mmol/L.Therefore, to cause the BAR contraction be not contained K in the antelope rhizome of chuanxiong capsule to antelope rhizome of chuanxiong capsule
+Cause.Ca among the antelope rhizome of chuanxiong capsule ED50 2.33mg/ml
2+The above method of content be calculated as 0.0088mg/ml, i.e. 0.218mmol/L is far below Ca in the Krebs ' physiology body lotion
2+Content (2.5mmol/L).Because, Ca on film
2+Passage is not stimulated under the open situation, slight Ca
2+The rising of concentration generally can not brought out tangible contractile response, thus can think antelope rhizome of chuanxiong capsule cause the BAR contraction neither antelope rhizome of chuanxiong capsule in contained Ca
2+Cause.
Sum up: migraine is a kind of repeated relapsing headache.Its cause of disease, pathology are still not fully aware of so far.It is generally acknowledged that psychentonia, the outer vasomotion of intracranial are one of cause of disease of primary disease morbidity unusually.
The BAR contractile response that experiment showed, more than that antelope rhizome of chuanxiong capsule can reduce mice elicitation activities number, strengthens pentobarbital sodium in mice sleep effect, reduces that acetic acid causes the mouse writhing reaction times, prolongs that thermostimulation causes the mice pain response time, reduces the Medulla Leporis seu Oryctolagi vascular resistance, cerebral blood flow increasing amount, antagonism KCI, NE, 5-HT is brought out.Show that antelope rhizome of chuanxiong capsule has tangible calmness, analgesia, releasing cerebral vasospasm, improves the effect of cerebral circulation.This effect may be that antelope rhizome of chuanxiong capsule has one of mechanism of well preventing and treating effect to migraine.
Obtain in the isolated experiment freshly prepared antelope rhizome of chuanxiong capsule can cause that BAR shrinks (usefulness and 5-HT, NE are suitable, but are weaker than KCI) again can antagonism KCI, NE, 5-HT is to the contraction of BAR.It shrinks the BAR mechanism of action, and more than experiment contains K except that having made antelope rhizome of chuanxiong capsule
+, Ca
2+Outside the quantitative determination, do not do further and probe into.But according to K
+, Ca
2+Content detection result and the antelope rhizome of chuanxiong capsule medicinal liquid of preparation above 24 hours do not produce tangible BAR contraction and do not observe cerebral vascular resistance rising phenomenon at body Medulla Leporis seu Oryctolagi circulation experiment, can infer, its vasoconstriction effect may be done for some vaso-active substance that is easy to inactivation, is worth further research.Effect as for its antagonism KCI, NE, 5-HT shrink BAR may be mainly due to the contained Radix Notoginseng of antelope rhizome of chuanxiong capsule.Many experiments have proved that the effective constituent arasaponin that mainly contains of Radix Notoginseng has calcium antagonism, energy antagonism KCI, the pressor effect of NE, 5-HT.
(2) antelope rhizome of chuanxiong capsule acute toxicity test mtd test
1, medicine
Antelope rhizome of chuanxiong capsule face with preceding with mortar with its abundant porphyrize, be made into the suspendible medicinal liquid (pH6.4) of 25% concentration then with 1% sodium carboxymethyl cellulose liquid dissolving.
2, animal
24 of NIH kind mices, ♀ ♂ half and half, body weight 18.5-21.5g provides (quality certification number 93022) by Department of Health of Guangdong Province medical experimental animal field.Fasting 12h before the test, but give 5% sugar-salt-water from drink.
3, method and result
Carry out acute toxicity test (mtd test) by literature method.Give mouse stomach 1 day with antelope rhizome of chuanxiong capsule 25% concentration (Cmax), 0.40ml/10g body weight (the mouse stomach maximum is accepted volume), 2 times on the 1st (being separated by 2 hours) dosage 20.0g/kg (be equivalent to approximately clinical 60kg adult consumption 50mg/kg 400 times).Administration time 8-10 in morning point.Room temperature 30 degree were observed 7 days after the administration.
The result is: except that most of mice activity reduces to some extent in 2 hours after being subjected to medicine, and all the other Non Apparent Abnormalities performances.Chiropractic is put to death mice, carries out breast, abdominal cavity, the dissection of cranium brain, sees also Non Apparent Abnormality of each internal organs.Therefore, antelope rhizome of chuanxiong capsule is to the LD of mouse stomach approach
50Greater than 20g/kg.
(3) antelope rhizome of chuanxiong capsule long term toxicity research
1, medicine:
Antelope rhizome of chuanxiong capsule face with preceding with mortar with its abundant porphyrize, be made into the suspendible medicinal liquid (PH6.4～6.8) of desired concn then with 1% carboxyl methyl cellulose sodium liquid dissolving.
2, animal:
It is rat that Sprage-dawley (SD) plants, body weight 70-95g, and ♀ ♂ half and half, healthy unpregnancy is provided by medical experimental animal field, Guangdong Province (postcode 510180), produces the quality certification numbers 93021.Rat (25～32 ℃ of room temperatures, low noise is raised in cages) under experimental situation is raised a week, discards the rat that body weight difference surpasses average weight 20%.Remaining rat is used for formal experiment.
3, method:
120 of SD rats, body weight 85 ± 11g is divided into matched group and antelope rhizome of chuanxiong capsule 500,1500,5000mg/kg body weight group, 30 every group with homeostatic principle at random.Irritate the stomach administration.The administration volume is the 20ml/kg body weight.Administration time 8-10 in morning point, administration every day 1 time, continuous 6 weeks (clinical course of treatment of this medicine is 10 days).Matched group gives 1% sodium carboxymethyl cellulose liquid of 20ml/kg body weight and irritates stomach.Observe following index:
1) ordinary circumstance: observe situations such as rat outward appearance, behavioral activity, feed and feces character.
2) growing state: per 2 weeks claim rat body weight 1 time.
3) hematologic parameter: after 6 weeks of administration, measure 1 time.Select content of hemoglobin (Hb), erythrocyte (RBC) for use, not knit projects such as erythrocyte (RRBC), platelet (PLT), numeration of leukocyte (WBC) and classification.Broken end is got blood.Measure RBC, RRBC, WBC and Hb content with the sub-blood cell of Britain's electrogenesis, hemoglobin counting instrument, under optical microscope, carry out the WBC classification.PLT measures with the ammonium oxalate direct counting method.
4) liver function: after 6 weeks of administration, measure 1 time.Broken end is got blood.Extract serum routinely.Press reitman-frankel method with homemade 721 type spectrophotometers and measure serum glutamic pyruvic transminase (SGPT) activity.Reagent is Guangzhou Hua Chang scientific and technological development company limited product.
5) renal function: after 6 weeks of administration, measure 1 time.Broken end is got blood.Extract serum routinely.Pressing picric acid-with homemade 721 type spectrophotometers removes protein method and measures serum creatinine (Cr) content, press urase-Betherlot method mensuration serum urea nitrogen (BUN) content.Reagent also is Guangzhou Hua Chang scientific and technological development company limited product.
6) vitals tissue pathology checking: after 6 weeks of administration, the sacrificed by decapitation rat is immediately taken out brain, the heart, lung, liver, stomach, spleen, caecum, kidney, adrenal gland, testis or ovary, its health status of perusal.Before get each internal organs fritter and put 10% formalin liquid internal fixation, the system wax disk(-sc) is cooked pathologic finding under optical microscope.
4, date processing:
Experimental data is represented with " mean ± standard deviation ".Group difference significance test measurement data is checked the enumeration data X 2 test with variance analysis or t.
5, result:
1) ordinary circumstance: after the administration, each organizes rat outward appearance health, and feces is shaped, behavioral activity and the equal Non Apparent Abnormality of feed situation.
2) growing state: different times is respectively organized rat body weight and is seen Table 5.Each organizes the equal no significant difference of weight ratio of rat.
3) hematologic parameter: each is organized the hematologic parameter check result and sees Table 6.As seen, after 6 weeks of administration, each organizes hematologic parameter does not have significant difference.
4) liver, renal function: after 6 weeks of administration, each organizes serum SGPT, BUN, Cr does not see notable difference (table 7).
5) the vitals tissue slice is checked: each internal organs perusal shows no obvious abnormalities.Its tissue slice inspection shows to have only the slight congestion of lung tissue except that 2 of matched groups, 1 of antelope rhizome of chuanxiong capsule 500mg/kg group, antelope rhizome of chuanxiong capsule 5000mg/kg group 2 and shows no obvious abnormalities.Lung tissue congestion rate difference shows no significance meaning (P＞0.05) through X 2 test between each group.
Table 5: each organizes rat body weight (g) relatively
| Time | Matched group | Antelope rhizome of chuanxiong capsule 500mg/kg group | Antelope rhizome of chuanxiong capsule 1500mg/kg group | Antelope rhizome of chuanxiong capsule 5000mg/kg group |
| Administration preceding 2 all backs are after 46 weeks of back week | 85±12 153±26 195±31 229±35 | 88±12 155±18 208±30 236±30 | 84±9 156±18 192±21 225±29 | 83±9 154±13 190±16 226±28 |
N is 30; Compare with matched group, all p＞0.05.
Table 6: respectively organize the rat blood mathematic(al) parameter after 6 weeks of administration relatively
| Project | Matched group | Antelope rhizome of chuanxiong capsule 500mg/kg group | Antelope rhizome of chuanxiong capsule 1500mg/kg group | Antelope rhizome of chuanxiong capsule 5000mg/kg group |
| Hb(g/L) RBC(×10 12/L) RRBC(％) PLT(×10 9/L) WBC(×10 9/ L) leaflet granulocyte (%) stab form granulocyte (%) eosinophilic granulocyte (%) | 141±11 4.99±0.37 3.7±1.1 239±68 15.5±4.1 30±12 0.70±0.9 0.10±0.45 | 140±9 4.96±0.32 4.0±1.7 260±45 16.5±3.4 32±8 0.60±0.68 0.05±0.22 | 140±8 4.95±0.25 3.8±1.2 231±67 16.5±3.6 33±10 0.85±0.81 0.35±0.59 | 139±12 4.91±0.42 4.3±1.5 229±73 16.7±4.3 29±6 1.20±0.83 0.05±0.22 |
| Lymphocyte (%) mononuclear cell (%) | 68±13 1.0±1.0 | 66±9 1.4±1.2 | 65±11 1.1±1.3 | 68±6 1.5±1.0 |
N is 30; Compare with matched group, all p＞0.05.
Table 7: respectively organize rat SGPT (Lai Shi unit), BUN (mg%), Cr (mg%) after 6 weeks of administration relatively
| Project | Matched group | Antelope rhizome of chuanxiong capsule 500mg/kg group | Antelope rhizome of chuanxiong capsule 1500mg/kg group | Antelope rhizome of chuanxiong capsule 5000mg/kg group |
| SGPT | 15.1±8.0 | 16.6±8.3 | 15.3±6.4 | 16.4±6.6 |
| BUN | 14.6±2.5 | 14.3±2.3 | 14.7±3.0 | 15.0±2.6 |
| Cr | 0.98±0.35 | 0.99±0.34 | 0.96±0.32 | 0.99±0.39 |
N is 30; Compare with matched group, all p＞0.05.
Discuss
This experiment irritates stomach 1 time for rat with antelope rhizome of chuanxiong capsule 500,1500 and 5000mg/kg dosage (be equivalent to approximately clinical 60kg adult consumption 50mg/kg body weight 10,30,100 times) every day, in continuous 6 weeks, obtain ordinary circumstance, growing state, hematologic parameter, serum SGPT activity, Cr, BUN content and the equal Non Apparent Abnormality of each organs and tissues cut sections for microscopic examination of rat.Show behavioral activity, growth promoter, hemopoietic function regulating liver-QI, the harmless effect of renal function to rat in this dosage range of antelope rhizome of chuanxiong capsule, vitals such as brain, the heart, lung, liver, stomach, spleen, caecum, kidney, adrenal gland, testis and ovary are not had pathogenic change effect.Prompting antelope rhizome of chuanxiong capsule generally overt toxicity can not occur by clinical administration mode (oral) and consumption long-term prescription.
(4) II, III phase clinical experiment.
Antelope rhizome of chuanxiong capsule has obtained Clinical Researches of New Drugs official written reply 2001ZL021 of National Drug Administration and the clinical additional official written reply 2001ZLb017 of new drug in calendar year 2001, has carried out clinical trial.
1, II phase clinical experiment
By at random, double blinding, simulation, positive drug parallel control, the research of multicenter II clinical trial phase, observed antelope rhizome of chuanxiong capsule to migraine (wind-yang and up-boring, channels discord card) clinical efficacy, safety and toxic and side effects and untoward reaction have been made preliminary assessment to its effectiveness and safety.
These EXPERIMENTAL DESIGN case 240 examples are observed qualified case 202 examples, reject or 6 examples that come off.Qualified case all meets inclusion criteria, selected back random packet.Wherein antelope rhizome of chuanxiong capsule test group is 102 examples, matched group 100 examples.Result of the test is as follows:
(1) effectiveness.
1) comprehensive therapeutic effect test group total effective rate 88.2%; Matched group is 80.0%.Two groups are compared P＜0.05, cure-remarkable-effectiveness rate (percentage rate of recovery from illness+produce effects) (as follows) treatment group is 51.0%, and matched group is 35.0%, statistical procedures P＜0.05, statistical significance is all arranged, illustrate that antelope rhizome of chuanxiong capsule test group comprehensive therapeutic effect total effective rate and cure-remarkable-effectiveness rate all are better than matched group.
2) total effective rate of pain palliation efficacy test group pain palliation efficacy and cure-remarkable-effectiveness rate are respectively 87.3% and 54.0%, two indexs of matched group are respectively 80.0% and 39.0%, learn by statistics and handle equal P＞0.05, illustrate that antelope rhizome of chuanxiong capsule is suitable with the control drug pain palliation efficacy, but treatment back headache degree compares P＜0.05 between two groups, illustrates that antelope rhizome of chuanxiong capsule alleviates headache degree aspect and is better than contrasting medicine.
3) tcm syndrome clinical trial group and matched group are treated all significantly reductions of back syndrome total mark, and self relatively has statistical significance P＜0.01; But not statistically significant P＞0.05 relatively between group, illustrate antelope rhizome of chuanxiong capsule have with contrast medicine similar improve traditional Chinese medical science wind-yang and up-boring, the get along well effect of syndrome of channels.
4) hemorheology and TCD influence blood examination whole blood contrast viscosity (low cut) and two indexs of packed cell volume have statistical significance (P＜0.05) after the medication of treatment group, more equal not statistically significant (P＞0.05) before and after other index medications and after two groups of medications illustrates that antelope rhizome of chuanxiong capsule improves viscosity of blood and erythrocyte deformability is better than contrasting medicine.
TCD checks that the blood samples of patients flow velocity shows statistical significance (P＜0.01) self more all arranged before and after two groups of treatments, but compare not statistically significant (P＞0.05) between two groups, antelope rhizome of chuanxiong capsule tool adjusting vasomotion is described, removes the cerebral vasospasm function, the function of tool analgesia and network is suitable with the matched group medicine.
(2) safety.
Test group and matched group routine blood test, routine urinalysis, stool routine, electrocardiogram treatment forward part case are unusual, treatment rear section case transfers to normally, it is unusual still having the part patient after unusual person treats before treating, do not increase the weight of the patient but have, two groups are not all had liver, renal dysfunction before and after the treatment, illustrate that this product clinical application is safe, safety is similar to the contrast medicine.Matched group has 1 example phenomenon to occur slightly having a sleepless night in process of the test, does not do any processing and continues administration.Insomnia disappears after 2 days.Show that more than two groups of medicines all have better safety.
2, III phase clinical experiment.
By at random, single blind, positive drug parallel control, the research of multicenter III clinical trial phase, further estimate of effectiveness and the safety of antelope rhizome of chuanxiong capsule to migraine treatment.
This test designs case 480 examples altogether, and actual selection case 440 examples are rejected or 16 examples that come off.Qualified case is 424 examples, and qualified case all meets inclusion criteria, selected back random packet.Wherein antelope rhizome of chuanxiong capsule for treating group is 319 examples, matched group 105 examples.Result of the test is as follows:
(1) effectiveness.
1) disease comprehensive therapeutic effect treatment comprehensive therapeutic effect evaluation in 30 days, two groups are compared p＜0.05, and statistical significance is arranged, and the test group comprehensive therapeutic effect is better than matched group; Follow up a case by regular visits to comprehensive therapeutic effect evaluation in 30 days, two groups are compared p＜0.05, and statistical significance is arranged, and the test group comprehensive therapeutic effect is better than matched group.
Treating 30 days disease comprehensive therapeutic effect total effective rate test group is 86.8%, and matched group is 76.2%, two group of relatively p＜0.05, and statistical significance is arranged, and the test group comprehensive therapeutic effect is better than matched group.Following up a case by regular visits to 30 days disease comprehensive therapeutic effect total effective rate test group is 86.8%, and matched group is 77.1%, two group of relatively p＜0.05, and statistical significance is arranged, and the test group comprehensive therapeutic effect is better than matched group.
Treating 30 days disease comprehensive therapeutic effect obvious effective rate test group is 52.0%, and matched group is 42.9%, two group of relatively p＞0.05, not statistically significant.Following up a case by regular visits to 30 days disease comprehensive therapeutic effect obvious effective rate test group is 51.1%, and matched group is 41.9%, two group of relatively p＞0.05, not statistically significant.
The disease integrated integral improved carry out statistical analysis and find, 21 days, 30 days, follow up a case by regular visits to 30 days integrated integrals and improve relatively p＜0.05 of project test group and matched group, statistical significance is arranged, the improvement of test group integrated integral is better than matched group; And 7 days, 14 days integrated integrals improve two groups of relatively p＞0.05, not statistically significant, and the improvement and the matched group of test group integrated integral are suitable.
2) tcm syndrome curative effect treatment tcm syndrome therapeutic evaluation in 30 days, two groups are compared p＜0.05, statistical significance are arranged; Test group tcm syndrome curative effect is better than matched group.Follow up a case by regular visits to tcm syndrome therapeutic evaluation in 30 days, two groups are compared p＞0.05, not statistically significant, and test group tcm syndrome curative effect and matched group are suitable.
Treating 30 days tcm syndrome curative effect total effective rate test group is 86.9%, and matched group is 74.3%, two group of relatively p＜0.01, and statistical significance is arranged, and test group tcm syndrome curative effect is better than matched group.Following up a case by regular visits to 30 days tcm syndrome curative effect total effective rate test group is 86.2%, and matched group is 75.2%, two group of relatively p＜0.01, and statistical significance is arranged, and test group tcm syndrome curative effect is better than matched group.
Treating 30 days tcm syndrome curative effect obvious effective rate test group is 46.1%, and matched group is 34.3%, two group of relatively p＜0.05, and statistical significance is arranged.Test group is described for the treatment wind-yang and up-boring, channels disharmony type migraine has significant curative effect, and obvious effective rate is better than matched group.Following up a case by regular visits to 30 days tcm syndrome curative effect obvious effective rate test group is 44.2%, and matched group is 36.2%, two group of relatively P＞0.05, not statistically significant.
The tcm syndrome integration improve 21 days, 30 days, follow up a case by regular visits to 30 days two groups of p＜0.05 relatively, statistical significance is arranged, and the improvement of test group tcm syndrome integration is better than matched group, 7 days, 14 days two groups of comparison p＞0.05, not statistically significant, test group tcm syndrome integration improves suitable with matched group.The prompting test group is better to the later stage curative effect that the tcm syndrome integration improves.
When therapeutic effect of syndrome evaluation severity extent was moderate in 30 days, two groups were relatively, Ridit difference 0.11, and test group is bigger by 11% than matched group.There is statistical significance P＜0.05.Therapeutic effect of syndrome was estimated other grade state of an illness and was followed up a case by regular visits to two groups of comparisons of 30 days severity extent grades, P＞0.05, not statistically significant in 30 days.Illustrate that test drug is better than contrasting medicine to the moderate headache curative effect for the treatment of 30 days.
3) 3 days pain palliation efficacies of 3 days pain palliation efficacies compare for two groups, average Ridit difference 0.082, and test group is bigger by 19% than matched group, and there is statistical significance p=0.012＜0.05, and 3 days pain palliation efficacies of test group are better than matched group.
3 days pain palliation efficacy total effective rates of test group are 87.1%, and matched group pain palliation efficacy total effective rate is 76.2%, two group and compares that there is statistical significance p=0.007＜0.01, and 3 days pain palliation efficacies of test group are better than matched group.
21 days, 30 days, follow up a case by regular visits to the statistical analysis that the headache of 30 days tcm syndrome primary symptoms improves and show, test group and matched group be p＜0.05 relatively, statistical significance is arranged, test group is better than matched group to tcm syndrome primary symptom headache improvement, and the headache of 7 days, 14 days tcm syndrome primary symptom improves two groups of relatively p＞0.05, headache improves suitable with matched group to the tcm syndrome primary symptom for not statistically significant, test group.Improve in the headache degree, the statistical analysis of pain relieving onset time, headache extinction time project, point out two groups of relatively p＞0.05, not statistically significant, test group is improved in the headache degree, pain relieving onset time, headache extinction time are suitable with matched group.The statistical analysis that the headache outbreak persistent period improves is found, 21 days, 30 days, follow up a case by regular visits to 30 days two groups of p＜0.05 relatively, statistical significance is arranged, the test group minimizing headache outbreak persistent period is better than matched group, and 7 days, 14 days two groups of comparison p＞0.05, it is suitable with matched group that not statistically significant, test group reduce the headache outbreak persistent period.The headache seizure frequency improved in 30 days, test group is bigger by 12% than matched group, two groups are compared p＜0.05, statistical significance is arranged, test group is better than matched group to the improvement of headache seizure frequency, follow up a case by regular visits to 30 days headache seizure frequencies and improve two groups of relatively p＞0.05, not statistically significant, test group is suitable to the improvement and the matched group of headache seizure frequency.
When pain palliation efficacy evaluation severity extent grade was moderate in 3 days, two groups were relatively, Ridit difference 0.10, and test group is bigger by 10% than matched group, and there is statistical significance P=0.015＜0.05.Other severity extent grade compares P＞0.05, not statistically significant for two groups.Show that antelope rhizome of chuanxiong capsule is better than contrasting medicine to the acute analgesic effect of moderate headache.
4) minor symptom curative effect antelope rhizome of chuanxiong capsule is in the improvement of neural mental symptom, and the curative effect of improving of symptoms such as dizzy, xerostomia is better than matched group, and all the other projects are p＞0.05 relatively, not statistically significant; And other symptoms, sign such as menstrual cycle, picture of the tongue, pulse condition improve the aspect, two groups of p＞0.05 relatively, not statistically significant.
5) in the hemorheology curative effect blood examination whole blood contrast viscosity height cut, low cut, plasma viscosity, packed cell volume, five project test group of erythrocyte aggregation index and matched group p＞0.05 relatively, equal not statistically significant.Illustrate that antelope rhizome of chuanxiong capsule reduces the effect of blood viscosity and contrast medicine suitable.
6) each each center curative effect of center curative effect comparative test group relatively has statistical significance, may cause because of local climate condition difference, and same this situation that exists in pharmaceutical production listing back can think that this allows.
(2) safety.
No bad incident takes place in the whole test, matched group has 1 routine drug combination, concrete condition is as follows: the old XX of patient, No. 25, medicine numbering, random number 489176, packet number 0, on January 23rd, 2003 was gone into group, and the patient brought into use estazolam because sleep is poor on the 1st in December in 2002, every day dosage 2mg, when using to off-test always (March 24 in 2003) still using this medicine.This case is as coming off case.From the analysis of adverse events, health check-up index and three aspects of lab testing as can be known, investigational agent is safe.
Above clinical trial shows that the clinical efficacy of antelope rhizome of chuanxiong capsule for treating migraine (wind-yang and up-boring, channels discord card) is remarkable, and long-term efficacy is good, toxic and side effects is little, is worth clinical expansion.
Further specify the present invention by the following examples
Embodiment 1: the preparation of capsule
Cornu Saigae Tataricae 25g Rhizoma Chuanxiong 25g Scorpio 25g
Scolopendra 4.5g Radix Paeoniae Alba 60g Bombyx Batryticatus 30g
Radix Angelicae Dahuricae 25g Ramulus Uncariae Cum Uncis 30g Radix Notoginseng 12g
Radix Rehmanniae 30g Radix Glycyrrhizae Preparata 10g
Starch is an amount of
Make 1000 of capsules (0.24g/ grain)
[preparation technology] above ten be Chinese medicine simply, gets Cornu Saigae Tataricae, Scorpio, Scolopendra, Bombyx Batryticatus, the Radix Notoginseng five tastes, sterilization, and oven dry is ground into fine powder, mixing.Get the Radix Paeoniae Alba, the Radix Angelicae Dahuricae, Radix Rehmanniae, Radix Glycyrrhizae Preparata four flavors, decoct with water secondary, each 1 hour.Filter, merging filtrate, being concentrated into relative density is the clear paste of 1.15～1.20 (90～95 ℃).Rhizoma Chuanxiong, Ramulus Uncariae Cum Uncis two flavors, with 80% ethanol extraction secondary, each 2 hours.Filter, merging filtrate, being concentrated into relative density is the clear paste of 1.15～1.20 (90～95 ℃).Merge above-mentioned two clear paste, stir evenly.Add appropriate amount of starch and above-mentioned fine powder, mixing, drying incapsulates, and makes 1000, promptly.
Embodiment 2: the preparation of tablet
Cornu Saigae Tataricae 25g Rhizoma Chuanxiong 25g Scorpio 25g
Scolopendra 4.5g Radix Paeoniae Alba 60g Bombyx Batryticatus 30g
Radix Angelicae Dahuricae 25g Ramulus Uncariae Cum Uncis 30g Radix Notoginseng 12g
Radix Rehmanniae 30g Radix Glycyrrhizae Preparata 10g
Starch is an amount of
Make 1000 of sheets
[preparation technology] above ten be Chinese medicine simply, gets Cornu Saigae Tataricae, Scorpio, Scolopendra, Bombyx Batryticatus, the Radix Notoginseng five tastes, sterilization, and oven dry is ground into fine powder, mixing.Get the Radix Paeoniae Alba, the Radix Angelicae Dahuricae, Radix Rehmanniae, Radix Glycyrrhizae Preparata four flavors, decoct with water secondary, each 1 hour.Filter, merging filtrate, being concentrated into relative density is the clear paste of 1.15～1.20 (90～95 ℃).Rhizoma Chuanxiong, Ramulus Uncariae Cum Uncis two flavors, with 80% ethanol extraction secondary, each 2 hours.Filter, merging filtrate, being concentrated into relative density is the clear paste of 1.15～1.20 (90～95 ℃).Merge above-mentioned two clear paste, stir evenly.Add appropriate amount of starch and above-mentioned fine powder, mixing, drying is granulated, and is pressed into 1000, promptly.
Claims (8)
1, the present invention is a kind of Chinese medicine preparation, it is characterized in that, is made by following Chinese medicine raw materials by weight proportion:
2 parts～9 parts of 12 parts～50 parts Scolopendras of 12 parts～50 portions Scorpios of 12 parts～50 parts Rhizoma Chuanxiongs of Cornu Saigae Tataricae
15 parts～60 parts of 12 parts～50 parts Ramulus Uncariae Cum Uncis of 15 parts～60 parts Radixs Angelicae Dahuricae of 30 parts～120 parts Bombyx Batryticatus of the Radix Paeoniae Alba
5 parts～20 parts of 15 parts～60 parts Radix Glycyrrhizae Preparata of 6 parts～24 portions Radix Rehmanniae of Radix Notoginseng.
2, the Chinese medicine preparation of claim 1 is characterized in that, is made by following Chinese medicine raw materials by weight proportion:
3 parts～6 parts of 19 parts～33 parts Scolopendras of 19 parts～33 portions Scorpios of 19 parts～33 parts Rhizoma Chuanxiongs of Cornu Saigae Tataricae
23 parts～39 parts of 19 parts～33 parts Ramulus Uncariae Cum Uncis of 23 parts～39 parts Radixs Angelicae Dahuricae of 46 parts～78 parts Bombyx Batryticatus of the Radix Paeoniae Alba
7 parts～13 parts of 23 parts～39 parts Radix Glycyrrhizae Preparata of 9 parts～16 portions Radix Rehmanniae of Radix Notoginseng.
3, the Chinese medicine preparation of claim 2 is characterized in that, is made by following Chinese medicine raw materials by weight proportion:
4.5 parts of 25 parts of Scolopendras of 25 portions of Scorpios of 25 parts of Rhizoma Chuanxiongs of Cornu Saigae Tataricae
30 parts of 25 parts of Ramulus Uncariae Cum Uncis of 30 parts of Radixs Angelicae Dahuricae of 60 parts of Bombyx Batryticatus of the Radix Paeoniae Alba
10 parts of 30 parts of Radix Glycyrrhizae Preparata of 12 portions of Radix Rehmanniae of Radix Notoginseng.
4, the Chinese medicine preparation in the claim 1～3 is to be fit to medicinal various dosage forms.
5, the Chinese medicine preparation of claim 4 is pill, powder, granule, tablet, lozenge, soft extract, syrup, mixture, drop pill, capsule, medicated wine, tincture, extractum.
6, the Chinese medicine preparation of claim 4 is capsules.
7, the Chinese medicine preparation of claim 1 prevents and/or treats application in the migrainous medicine in preparation.
8, the preparation method of the Chinese medicine preparation of claim 1 is characterized in that, may further comprise the steps:
A, get Cornu Saigae Tataricae, Scorpio, Scolopendra, Bombyx Batryticatus, the Radix Notoginseng five tastes, sterilization, oven dry is ground into fine powder, mixing.
B, get the Radix Paeoniae Alba, the Radix Angelicae Dahuricae, Radix Rehmanniae, Radix Glycyrrhizae Preparata four flavors, decoct with water secondary, each 1 hour.Filter, merging filtrate, being concentrated into relative density is the clear paste of 1.15～1.20 (90～95 ℃).
C, get Rhizoma Chuanxiong, Ramulus Uncariae Cum Uncis two flavors,, add 8 times of amounts at every turn and extracted 2 hours with 80% ethanol extraction secondary.Filter, merging filtrate, filtrate is concentrated into the clear paste that relative density is 1.15～1.20 (90～95 ℃).
D, merge above-mentioned two kinds of clear paste, stir evenly, add above-mentioned fine powder and medicine can accept carrier, mixing is made preparation.
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Cited By (3)
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| CN102028783A (en) * | 2011-01-05 | 2011-04-27 | 朱良春 | Pain-relieving capsules, production method thereof and application thereof |
| CN102727834A (en) * | 2012-07-18 | 2012-10-17 | 南京中医药大学 | Traditional Chinese medicine composition for treating migraine, and preparation method and application thereof |
| CN103638330A (en) * | 2013-12-23 | 2014-03-19 | 卢秀霞 | Traditional Chinese medicine preparation for treating qi-blood deficiency type migraine and preparation method thereof |
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2006
- 2006-04-07 CN CNB2006100348621A patent/CN100571729C/en active Active
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102028783A (en) * | 2011-01-05 | 2011-04-27 | 朱良春 | Pain-relieving capsules, production method thereof and application thereof |
| CN102727834A (en) * | 2012-07-18 | 2012-10-17 | 南京中医药大学 | Traditional Chinese medicine composition for treating migraine, and preparation method and application thereof |
| CN102727834B (en) * | 2012-07-18 | 2013-09-04 | 南京中医药大学 | Traditional Chinese medicine composition for treating migraine, and preparation method and application thereof |
| CN103638330A (en) * | 2013-12-23 | 2014-03-19 | 卢秀霞 | Traditional Chinese medicine preparation for treating qi-blood deficiency type migraine and preparation method thereof |
| CN103638330B (en) * | 2013-12-23 | 2015-11-18 | 卢秀霞 | One treats migrainous Chinese medicine preparation of QIXUELIANGXU type and preparation method thereof |
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| CN100571729C (en) | 2009-12-23 |
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Effective date of registration: 20171213 Address after: 225321 Yangtze River Jiangnan Road, Taizhou, Zhejiang Province, the Yangtze River, the Yangtze River Pharmaceutical Group Co., Ltd. No. 1, Jiangsu Patentee after: Yangtze River Pharmaceutical Co., Ltd. Address before: 523109 Dongguan City, Guangdong Province, Dongcheng camphor industrial area Patentee before: Guangdong Winnerway Group Pharmaceutical Co., Ltd. |
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Effective date of registration: 20211215 Address after: 225300 No. 9, Longfeng Tang Road, Yongan Town, Taizhou, Jiangsu. Patentee after: YANGZIJIANG PHARMACEUTICAL GROUP JIANGSU LONGFENGTANG TRADITIONAL CHINESE MEDICINE Co.,Ltd. Patentee after: Yangzi River Pharmaceutical Group Co., Ltd. Address before: 225321 Yangzi Pharmaceutical Group Co., Ltd., No. 1 Yangzi Jiangnan Road, Taizhou, Jiangsu Patentee before: YANGTZE RIVER PHARMACEUTICAL GROUP Co.,Ltd. |