CN1274318C - Medicine for treating hemicrania - Google Patents

Abstract

The present invention discloses a novel Chinese herbal medicine for treating migraine, which is prepared from the following components: 10 to 25 parts by weight of cynanchum paniculatum, 5 to 20 parts by weight of dahurian angelica and 5 to 20 parts by weight of notoptetygium. The present invention has the advantages of unique formulation, few medicine doses, convenient manufacture, low cost, outstanding curative effect and fast effect taking, and the present invention can quickly relieve the symptoms of the migraine.

Description

Treat migrainous medicine

1. technical field

The present invention relates to the migrainous medicine of a kind of treatment, is to be the Chinese patent medicine of feedstock production with the Chinese herbal medicine specifically.

2. background technology

Migraine is a kind of clinical common disease of outbreak repeatedly, and the migraine prevalence is higher, is about for 985.2/10 ten thousand/year, and 8% man and 25% woman can suffer from this disease in life at it.Though the Epidemiological study of China finds no mortality rate, the outbreak that it is frequent has a strong impact on patient's physical and mental health, daily life and work and study.

Mainly there is problem in migrainous treatment both at home and abroad at present:

(1) the western medical treatment primary disease mostly is anti symptom treatment such as analgesia, calmness, emesis, adopt Ergotamine preparation, Qu Putan class medicine mostly, these medicines often have side reactions such as dizziness, nauseating, drowsiness, gastrointestinal irritation, paraesthesia, take analgesic for a long time or often and still can cause the analgesic nephropathy.

(2) the Chinese medicine primary disease has certain advantage, but thinks the not outer excessive rising of liver-YANG of migrainous pathogenesis, phlegm-turbidity and blood stasis blood, deficiency of qi and blood more, and method of treatment is manyly reduced phlegm to relieve dizziness, high fever, infantile convulsions, epilepsy, etc., benefiting QI for activating blood circulation.And clinically the patient with the ailment said due to cold or exposure be mostly suffer from, hematogenous blockage be pathogenesis this, so relieve dizziness, high fever, infantile convulsions, epilepsy, etc. reduce phlegm, the benefiting QI for activating blood circulation migraine pathogenesis that can not hit fully is at all.

(3) various medicines are taked traditional oral administration method more, medicine is slow in gastrointestinal absorption, the inhibition of the first-pass effect of liver and blood brain barrier in addition, it is very slow that effective ingredient arrives the speed of diseased region in the brain, measure also few, thereby influenced clinical efficacy, onset is also slow, does not reach the effect of rapid alleviation cephalagra.

3. summary of the invention

The present invention is in order to overcome above deficiency, and is basic for trouble, hematogenous blockage pathogenesis at the migraine ailment said due to cold or exposure, a kind of determined curative effect is provided, can alleviates cephalagra rapidly, has been the medicine of raw material with the Chinese herbal medicine.

Another object of the present invention provides the preparation method of this migraine treatment medicine.

Solution of the present invention is based on the understanding of motherland's medical science to migraine pathogeny and Therapeutic Principle, by clinical observation for many years, finds that migraine is that ailment said due to cold or exposure is to suffer from haunting, and because of wind having the nature of shifting, so the disease of holding concurrently up and down is numerous, wind having the nature of frequent change is when so not work is no; And the patient is outbreak repeatedly how, with the passing of time must the stasis of blood, so ailment said due to cold or exposure for suffer from, hematogenous blockage is its basic pathogenesis.Its treatment is controlled outside the wind when hitting pathogenesis, still should note invigorating blood circulation, and gets the blood sector-style from the meaning of going out, and drafts the expelling wind and activating blood circulation analgesic therapy and is its method of treatment.Consulting lot of documents at all times, and sum up secular clinical position experience, achieve with reference to modern pharmacological research, several different methods such as utilization logistic regression analysis, cluster analysis, principal component analysis, factorial analysis, filter out the medicine of effect with expelling wind and activating blood circulation analgesic therapy, according to traditional Chinese medical science prescription combination principle, preferably get, bring into play the effect of its emergency of radicallying reform, ease pain.

Medicine of the present invention is made (consumption is a weight portion) by following component:

5～20 parts of 5～20 portions of Rhizoma Et Radix Notopterygiis of 10～25 parts of Radixs Angelicae Dahuricae of Radix Cynanchi Paniculati

The formula optimization weight proportion scope of preparation medicine of the present invention is:

8～15 parts of 8～15 portions of Rhizoma Et Radix Notopterygiis of 12～20 parts of Radixs Angelicae Dahuricae of Radix Cynanchi Paniculati

The optimum weight proportioning of medicine of the present invention is:

10 parts of 10 portions of Rhizoma Et Radix Notopterygiis of 15 parts of Radixs Angelicae Dahuricae of Radix Cynanchi Paniculati

Medicine of the present invention can be a said dosage form on any pharmaceutics; Nasal drop preferably.

Above-mentioned each component is made medicine production method of the present invention is:

(1) gets Radix Cynanchi Paniculati, the Radix Angelicae Dahuricae, Rhizoma Et Radix Notopterygii drying and crushing to 120 order fine powder earlier; (2) fine powder mixed add 30% sodium chloride solution, distillation reclaim distillate; (3) distillate is concentrated standardize solution, add solubilizing agent, the sterilization bottling.

The present invention mainly contains following important feature:

(1) three herbal medicines all contain abundant volatile oil component among the present invention, contain paeonol as Radix Cynanchi Paniculati, and the Radix Angelicae Dahuricae contains Radix Angelicae Dahuricae element, Rhizoma Et Radix Notopterygii contains multiple coumarin, because these materials are fat-soluble all very strong, sees through biomembrane easily, easily be absorbed by the body and transport, better bioavailability is arranged.

(2) modern pharmacological research shows, three herbal medicines all can obviously improve the threshold of pain of hot plate method experiment mice among the present invention, reduce mice acetic acid twisting reaction times, better analgesic activity is arranged, and experimentation and the clinical observation of passing through us are found, they have very significant synergism, can alleviate migraine rapidly and cause simultaneous phenomenon.

(3) medicine of the present invention can pass through nasal-cavity administration, goes into brain through Nasal Mucosa Absorption and mainly contains 3 paths: olfactory neural pathway, olfactory mucosa epithelium path and blood circulation path.All to absorb directly into brain relevant with medicine for preceding two paths.But other zones beyond the drug molecule through mucous membrane epithelium nervi olfactory unit recipient cell enter sustenticular cell and glandular cell by pinocytosis or diffusion. also can pass intercellular substance and enter intercellular fluid.If drug molecule passes basement membrane and enters lamina propria, enter cerebrospinal fluid thereby will enter the transhipment of nervi olfactory bundle peripheral clearance.If the drug molecule that is transported to basement membrane is near the aixs cylinder in the lamina propria, drug molecule will be transported to cerebrospinal fluid in the neuron peripheral cell.Most micromolecule are to be absorbed into brain by olfactory mucosa epithelium path, and the general absorption by olfactory neural pathway of this path is rapid, and this is confirmed by people such as Frey.Therefore can think that this route of administration is rapid-action, the bioavailability height, and patient's compliance is good, is that the ideal of migraine clinical administration approach is selected.In addition, " element is asked a Miao thorn Theory piece of writing " points out " husband's heresy Ke Da Network person, the right side is annotated on a left side, a right notes left side ", " evil objective in warp, left side Sheng is then right sick, and the right side is contained then left sick "; Wind be disease, the visitor is in the left side of head meridians, then the left side meridian qi and blood of head stop up to stagnate not all rightly, is that to be that a left side is contained then right sick, when control on the right side, so on the left of work as from the right side nasal-cavity administration during migraine nasal-cavity administration; In like manner, during right side migraine nasal-cavity administration when from the left side nasal-cavity administration.And Frey etc. proves the nasal absorption of I-NGF, radioactivity is at olfactory bulb after the administration, brain, brain occurs rapidly in the district, illustrate that radioactivity is after olfactory mucosa epithelial cell gap absorbs, transport outside born of the same parents along nervi olfactory unit path and to enter olfactory bulb and cerebrospinal fluid, proof nervi olfactory unit path is that the nasal-cavity administration medicine is gone into one of brain major avenues of approach through Nasal Mucosa Absorption, and nervi olfactory intersects after going into brain, so have the theoretical foundation of modern neuroanatomy and pharmacokinetics during migraine from the offside nasal-cavity administration, also this just medication of our clinical experience is scientific and effective.

(4) it is few, simple for production, cheap to the invention provides the medicine flavour of a drug, determined curative effect, and onset is quick.

One, following is pharmacodynamic experiment of the present invention

1 grouping

50 of extracting male Wistar rats are divided into 5 groups at random, 10 every group: model group, medicine gastric infusion group of the present invention, drug nasal administration group of the present invention, Tai Ji TONGTIAN KOUFUYE nasal-cavity administration positive controls and blank group.

2 preparating liquids

Medicine of the present invention, Tai Ji TONGTIAN KOUFUYE are made into medicinal liquid.

3 nasal cavity Sequestrations

Medicine gastric infusion group of the present invention, the anesthesia of Tai Ji TONGTIAN KOUFUYE nasal-cavity administration positive controls ip pentobarbital sodium are kept breathing as tracheal intubation, on the esophagus that exposes, open an osculum. a polyethylene tube is passed straight through to the nasal cavity rear portion.Stick with glue agent nose palate passage is shut, in case medicinal liquid runs off from nasal cavity after the administration.

4 modelings

Blank group: do not give any processing factor; Model group, medicine gastric infusion group of the present invention, drug nasal administration group of the present invention, Tai Ji TONGTIAN KOUFUYE nasal-cavity administration positive controls are according to people's such as Cristina Tassorelli report, give rat skin lower injection Nitro-Bid 10mg/kg injection, duplicate experimental migraine animal model, it is rubescent ears to occur after 30 minutes, forelimb is frequently scratched one's head, and the symptom of climbing hints model animal head discomforts such as cage increased frequency is the index of modeling success.

5 administrations

Model group, blank are organized not administration; Medicine gastric infusion group of the present invention gavages medicine medicinal liquid 2ml of the present invention; Drug nasal administration group of the present invention is given 2ml medicine medicinal liquid of the present invention by nasal cavity; Tai Ji TONGTIAN KOUFUYE nasal-cavity administration positive controls is by nasal cavity Tai Ji TONGTIAN KOUFUYE.

6 SABC methods are measured c-fos

Rat is prostrate on the operation fixing head, keep normal body temperature.At distance bregma 6.5mm, a hole (penetrate cerebral dura mater, must not injure cerebral tissue), the about 1.2mm of diameter make a call in 1.5mm place, center line left side.

Meet list of references (DG Herrera, HA Robertson.Application of potassium chloride to thebrain surface induces the c-fos proto-oncogene:reversal by MK-801.Brain Res, 1990,510 (1): 166-170) carry out.

The counting of 7c-fos immuning positive cell

The counting of c-fos immuning positive cell is according to bilateral counting under the rat brain stereotaxic atlas mirror, gets about 3.5mm place behind the bregma, coronal section FrPaC, N, the simultaneous section statining in P district.Range of observation is bilateral FrPaC, N, and the P district, 3 different visuals field of counting, every district, field range is 0.2mm ², 2～3 sections of every animal counting are taken the mean.

8 statistical analysiss

All data are all imported the IBM/PC microcomputer, use the dBASE data base administration, data analysis 6.12 editions softwares of SAS, group data X ²Check, ranked data are analyzed with Ridit, and all measurement datas all adopt t check (representing with X ± S).

Experimental result

Table 1: the influence that medicine of the present invention is learned rat behavior

Group	Animal number of elements (n)	Dosage	Forelimb number of times difficult to tackle in 1 minute after the modeling (unit: inferior/minute)	Forelimb number of times difficult to tackle in 30 minutes after the administration (unit: inferior/minute)
					Blank group Nerve in Migraine Model group physiological saline collunarium group Tai Ji exceedingly high oral liquid gavage group medicine gavage of the present invention group medicine collunarium of the present invention group	10 10 10 10 10 10	--isometric(al) NS 1.7ml/k g 3.33ul/ kg 3.33ul/ kg	0 40.60±1.90 40.40±2.00 40.70±1.77 40.80±1.55 40.30±1.64	0 38.90±1.52 39.10±1.66 △☆ 17.50±1.96 8.80±1.32 * 0.60±0.70 **★

The result: normal saline group and blank group comparison ▲ P＜0.05, compare ☆ P＞0.05 with the Nerve in Migraine Model group; The stomach group irritated by medicine of the present invention and the Tai Ji TONGTIAN KOUFUYE is irritated the stomach group relatively ^*P＜0.05; Medicine collunarium group of the present invention and Tai Ji TONGTIAN KOUFUYE are irritated the stomach group relatively ^*P＜0.01; Medicine collunarium group group of the present invention and medicine of the present invention are irritated relatively ★ P＜0.01 of stomach group.

Table 2 medicine of the present invention is to the influence of migraine animal model c-Fos gene expression positive cell number (X ± s)

Group	Animal number of elements (n)	Dosage	Positive cell number
					Brain stem	Hypothalamus
			Blank group Nerve in Migraine Model group normal saline collunarium group Tai Ji TONGTIAN KOUFUYE is irritated stomach group medicine of the present invention and is irritated stomach group medicine collunarium of the present invention group	10 10 10 10 10 10			--isometric(al) NS 1.7ml/kg 3.33ul/kg 3.33ul/kg	62.81±59.31 335.25±189.62 * 329.15±190.32 153.93±93.68 132.19±90.02 ★ 68.15±57.73 **	87.63±67.34 371.87±291.52 * 367.77±289.41 183.26±124.17 151.35±126.58 ★ 95.56±64.18 **

The brain stem of the variation Nerve in Migraine Model group experimental rat of c-Fos gene expression positive cell number, hypothalamus c-Fos gene expression positive cell number showed increased, with the blank group relatively have utmost point significant difference ( ^*P＜0.01); The brain stem of Nerve in Migraine Model group experimental rat, hypothalamus c-Fos gene expression and normal saline collunarium group comparison there was no significant difference ( ^*P＞0.05); Medicine of the present invention is irritated stomach group, Tai Ji TONGTIAN KOUFUYE and medicine collunarium group of the present invention all has significant difference with blank group and Nerve in Migraine Model group; The brain stem of medicine collunarium group rat of the present invention, hypothalamus c-fos expression of gene positive cell number and medicine of the present invention irritate stomach group and Tai Ji TONGTIAN KOUFUYE irritate the stomach group relatively have significant difference ( ^*P＜0.01).

Two, following is clinical experiment of the present invention

For showing that medicine of the present invention to migrainous therapeutic effect, has carried out system's clinical observation.The basic principle of evidence-based medicine EBM clinical research is followed in this research, intends adopting the test method of random packet, double blind control to carry out clinical research.

1 case is selected

1.1 diagnostic criteria

1.1.1 tcm diagnosis standard: with reference to " the wind syndrome of head diagnosis and the efficacy assessment standard " of State Administration of Traditional Chinese Medicine's encephalopathy emergency case cooperative groups formulation in 1992

(1) primary symptom: repeated relapsing headache, the course of disease are more than 6 months or have 5 outbreaks at least.

1. painful sick position is many on head one side volume temporo, forehead, temporo top, or a left side or the right side toss about in bed outbreak or be full headache.

2. the character of pain mostly is jumping pain, twinge, distending pain, dusk pain, dull pain, or headache as split etc.

3. also there are lasting several weeks of person sustainable several minutes of the each outbreak of headache, a few hours, a couple of days, but spontaneous remission.

(2) acute or subacute onset, the start-stop impermanence.

(3) sick sending out can have inducement, and often there is premonitory symptom at the end before sending out.

(4) through neurologic check and physics and chemistry, CT, MRI, DSA check can except organic disease causer in cranial injury and the brain.

1.1.2 Western medicine diagnose standard: the migraine diagnostic criteria that the international women's head-ornaments pain of reference association was drafted in 1988.

(plain edition) of absence of aura:

(1) outbreak is more than at least 5 times;

(2) if do not treat, each outbreak continues 4～72 hours;

(3) has following feature, at least 2: 1. one-sided property; 2. pulsation; 3. degree be in or severe (daily life is limited or stop); 4. because of going upstairs or movable headache of other similar daily bodies increased the weight of.

(4) have at least between stage of attack one of following: 1. feel sick and/or vomiting; 2. photophobia and phonophobia

(5) have one of following feature: 1. medical history and physical examination have not been pointed out the organic disease foundation; 2. the prompting of medical history and physical examination has the organic disease foundation, but gets rid of through relevant lab testing; Though 3. certain organic disease is arranged, migrainous first outbreak and this disease do not have substantial connection.

Tendency (typical case) migraine is arranged

(1) meets following 2, show effect at least 2 times.

(2) meet following characteristics, at least 3: 1. have limitation cortex or (with) the handicapped premonitory symptom more than 1 or 1 of brain stem; 2. have 1 premonitory symptom at least, development gradually continued more than 4 minutes, or had two or more symptoms take place in succession; 3. premonitory symptom persistent period＜60 minute; 4. premonitory symptom is shown effect the no intermission with headache.(3) have 1 of following feature: 1. medical history and physical examination have not been pointed out the organic disease foundation; 2. the prompting of medical history and physical examination has the organic disease foundation, but gets rid of through relevant lab testing; Though 3. certain organic disease is arranged, migrainous first outbreak and this disease do not have substantial connection.

1.1.3 dialectical standard: with reference to the disconnected standard of waiting to see the doctor with reference to " wind syndrome of head diagnosis and efficacy assessment standard " wind stasis of blood of State Administration of Traditional Chinese Medicine's encephalopathy emergency case cooperative groups formulation in 1992.

The wind stasis of blood is waited: headache with the passing of time, outbreak repeatedly, aching as needle stabbing lancinates, or jumping pain, sore spot is fixing not to be moved, insomnia and dreamful sleep, menoxenia or clot is arranged with stomachache, purplish tongue or band ecchymosis, petechia, the Sublingual venation is livid purple, deep and hesitant pulse or string.

1.1.4 headache strength grading: with reference to international headache association criterion in 1988.

I level: not bitterly.

The II level: mild pain, but do not influence activity.

The III level: moderate pain, but do not stop action.

The IV level: moderate pain, can not the participation activity.

1.2 the standard of including in

(1) patient volunteers to participate in and signature Informed Consent Form person;

(2) meet above-mentioned Chinese and western medicine diagnostic criteria;

(3) have following one: seizure frequency 3 times every month at least, pain degree are serious, influence working and learning, in the past analgesic drug product fail to respond to any medical treatment or untoward reaction serious;

(4) meet wind blood stasis syndrome standard (having two deputy director Chinese physicians or above academic title personnel to approve jointly);

(5) age is in 18-70 year.

1.3 exclusion standard:

(1) headache that causes of other diseases;

(2) severe cardiac, liver, kidney disease, gestation or women breast-feeding their children;

(3) allergic constitution or (with) drug allergy history person arranged;

(4) being unwilling to accept research measure or other reasons can not the partner;

(5) migrainous specific type is as ophthalmoplegic migraine, hemiplegia type migraine etc.;

(6) age is at under-18s or more than 70 years old.

1.4 the experimenter withdraws from the condition of test

1.4.1 withdrawing from of researcher decision

(1) in the clinical trial process, some complication, complication have taken place the experimenter or special physiological changes, the person that is not suitable for continuing the reception test;

(2) experimenter's compliance is poor, influences effectiveness and safety judgement person;

(3) in double-blind trial, broken blind or promptly take off blind situation.

1.4.2 the experimenter withdraws from test voluntarily

According to the regulation of Informed Consent Form, the experimenter has the right to drop by the wayside test, though or the experimenter clearly propose to withdraw from test, no longer accept medication and detection and lose visit, these situations also should count and withdraw from or the case that comes off.Should understand the reason that it withdraws from as far as possible, can be divided into conscious unsatisfactory curative effect, to untoward reaction be difficult to stand, economic problems, other reasons can not continue reception test, undeclared reason etc., and record in addition.

2 cases source

Case derives from the outpatient service and the inpatient of 3 three grades of first-class institutes of traditional Chinese medicine such as Hospital Attached to Shandong Chinese Medical Univ..

3 group technologies

Adopt the method for designing of multicenter, stratified random, double blind controling test.Select migraineur's 150 examples, be divided into treatment group, placebo group, carry out clinical observation.Adopt at random, the method for double blinding, placebo, the double blind random table is by special messenger's design and control, and carries out whole end and take off blind and statistics.Situations such as selected patient's age, sex, family history, trauma history, medication history, merging premonitory symptom are carried out layering, balanced management.

3.1 estimation of sample size

Adopt " to the difference of two sample rates, the meaning that takes statistics is checked the size table of required sample size " to do the sample size estimation, and estimate that it is 20% that case is taken off the mistake rate, this test needs case 150 examples approximately.

3.2 random method

Adopt the research method of completely random contrast, table of random number produces with the SAS8.0 software programming, includes order in according to table of random number that produces and case the patient is divided respectively in matched group and the treatment group.

150 routine patients are by behind 1: 1: 1 pro rate to three center, 1 outside agency's keeping password envelope and random assortment card are selected in each center, when qualified experimenter enters research, take the identical envelope of sequence number in proper order apart by it, grouping is treated according to card regulation wherein, must not do any change.

3.3 contrast method

Because lack the Chinese medicine preparation of onset rapidly at present, blank is adopted in this research.

3.4 blind method

Adopt double-blind method, the medicinal liquid color of this development test group and matched group, packing are identical, and dose equates, and route of administration, method, number of times, consumption unanimity.The random cipher envelope is managed by the custodian, open envelope decision grouping after, the collaborative medicine monitor staff of custodian gives the clinical observation personnel medicine and uses under the situation of maintaining secrecy.A supervisor (professional not in the know of non-seminar) is established at each center, and the enforcement management of blind process and blind method is established in supervisor's supervision, does not directly participate in the observation and the data collection of clinical research.The full-time efficacy evaluation personnel (non-subject study personnel) that served as by the professional and technical personnel with statistical theory knowledge are established at each center, are responsible for the evaluation curative effect.After clinical research finishes and finishes data statistic analysis, take off blind by the random cipher custodial staff.Taking off blind process should have problem designer, researcher, supervisor, efficacy evaluation person and store keeping director on the scene.

4 Therapeutic Method

4.1 medicine: treatment group medicine of the present invention, to produce by pharmaceutical factory of Shandong Traditional Chinese Medicine University, every ml medicinal liquid contains crude drug 4.5g;

The matched group blank, the placebo of employing and the same outer package of medicine of the present invention, same quality, same dosage is produced by pharmaceutical factory of Shandong Traditional Chinese Medicine University.

4.2 administrated method: two groups of cases all adopt the administration of nasal-cavity administration mode, and at rayon balls top plug nose, right nose is filled in the left side headache with medicine liquid droplet, the left nose of right side headache plug, and the left and right sides nose of having a headache entirely is used alternatingly, each 30min, shared medicine 30 days.Interim respectively giving and medicine during the headache outbreak, and record onset time and headache extinction time.Ban use of the other treatment medicine during the treatment, as analgesics, tranquilizer, calcium ion antagonist, Ergotamine preparation etc.

5 observation index

5.1 safety is observed:

(1) general health check-up project;

(2) blood, urine, just routine test and liver, kidney function test, before and after the treatment each 1 time;

(3) untoward reaction.

5.2 health giving quality observation:

(1) headache index;

(2) platelet aggregation rate

(3) rein in (TCD) and observe cerebral blood flow through cranium is multispectral;

(4) time that headache is alleviated after times of headache, degree, persistent period, the administration;

6 curative effects are judged

6.1 efficacy evaluation adopts scoring method: (with reference to Ministry of Public Health " new Chinese medicine treatment migraine clinical research guideline " migraine point system)

Primary part observation times of headache, degree, persistent period, observe simultaneous phenomenon simultaneously.

(1) times of headache: to calculate by the moon, outbreak in every month is 6 minutes more than 5 times, and 3 times-5 times is 4 minutes, and being less than 2 times is 2 minutes.

(2) headache degree: need lie in bed during outbreak is 6 minutes, and the work that influences during outbreak is 4 minutes, and not influence work is 2 minutes during outbreak.

(3) the headache persistent period: continuing is 6 minutes more than 2 days, and continuing 12-48 hour is 4 minutes, and it is 2 minutes that the persistent period is less than 12 hours.

6.2 total effects evaluation criteria (with reference to Ministry of Public Health " new Chinese medicine treatment migraine clinical research guideline " migraine point system) adopts the nimodipine method:

[integration before (integration before the treatment-treatment back integration)/treatment] * 100%

(1) clinical recovery: finish no ictal cephalagra the course of treatment, and drug withdrawal was not recurred in 1 month.

(2) produce effects: treatment back integration reduces more than 50%.

(3) effective: treatment back integration reduces 21%-50%.

(4) invalid: treatment back integration reduces below 20%.

7 statistical analysiss

All data are all imported the IBM/PC microcomputer, use the dBASE data base administration, data analysis 6.12 editions softwares of SAS, group data X ²Check, ranked data are analyzed with Ridit, and all measurement datas all adopt t check (representing with X ± S).

The protection of 8 experimenter's rights and interests

The relevant clinical research test specification with China of Declaration of Helsinki (in October, 2000 Edinburg version) is followed in this research, rules are carried out.The clinical research scheme can be implemented after Ethics Committee's approval of test responsible department.

Before each subject enrollment, researcher must be complete to the experimenter, comprehensive purpose, degree and the possible risk of introduction research.Allow the experimenter know he have the right at any time to withdraw from the test and do not made reprisals.Please every a Informed Consent Form of subjects signed before selected.

9 quality controls and assurance

Before research, give training, be to participate in research worker research approach and every index content are fully understood and to be familiar with, for every index of regulation, should check according to scheme official hour and method, should note observing untoward reaction or unexpected fortuitous event.Make regular check on each central task, confirm that the implementation status of various indexs, affirmation scheme implementation reach appraisal standards, the authenticity and integrity of inspection record, and check experimenter's rights and interests protection situation.

10 results

Headache index variation before and after table 3 medicine group of the present invention and the placebo group treatment (X ± s)

Group	The example number	The headache index
				Before the treatment	After the treatment
		Medicine group placebo group of the present invention	75 75			132.87±9.15 130.02±9.52	40.12±3.68 *★ 128.37±4.13

Annotate: compare with placebo group ^*P＜0.01 is with preceding relatively ★ P＜0.01 of treatment.

Headache outbreak every month persistent period (X ± s, unit: h) before and after table 4 treatment

Project	Medicine group of the present invention (n=75)	Placebo group (n=75)
			After treating before the treatment	30.21±3.17 18.96±3.35 **	29.83±3.52 27.74±3.43

Annotate: with preceding relatively ★ P＜0.05 of treatment; Compare with placebo group ^*P＜0.05.

Every month attack times of headache before and after table 5 treatment (X ± s)

Project	Medicine group of the present invention (n=75)	Placebo group (n=75)
			After treating before the treatment	5.65±0.58 2.13±0.37 **	5.58±0.49 5.16±0.42

Annotate: with preceding relatively ★ P＜0.01 of treatment; Compare with placebo group ^*P＜0.01.

Headache is alleviated after table 6 administration time (X ± s, unit: h)

Project

Medicine group of the present invention (n=75)

Placebo group (n=75)

After treating before the treatment

19.75±25.34 5.48±16.26

17.98±26.15 15.76±19.83

Annotate: with preceding relatively ★ P＜0.01 of treatment; Compare with placebo group ^*P＜0.01.

Observation before and after the treatment of table 7 platelet aggregation rate (X ± s)

Project	Medicine group of the present invention (n=75)	Placebo group (n=75)
			After treating before the treatment	74.13±2.45 57.78±3.26	75.98±2.63 73.56±2.94

Annotate: with preceding relatively ★ P＜0.01 of treatment; Compare with placebo group ^*P＜0.01.

Check result (X ± s, unit: cm/s) before and after the table 8 TCD treatment

Project	Blood flow rate (cm/s)
										LMAC	RMAC	LACA	RACA	LPCA	RPCA
Before the treatment	Medicine group of the present invention (n=18)	153.11± 14.23	142.01 ±15.67	118.61± 16.42	136.27 ±13.12	78.24± 13.75	87.18± 16.78
								Placebo group (n=15)	156.24 ±15.18	147.89 ±13.37	116.85± 14.76	137.61 ±13.59	80.07± 12.39	84.62± 14.83
	After the treatment	Medicine group of the present invention (n=18)	102.51 ±13.62 ★*	98.36± 14.41 ★*	97.34± 15.07 ★*	98.81± 10.54 ★*	75.34± 11.06 *								81.79± 11.58 *
Placebo group (n=15)								154.17 ±14.33	144.76 ±15.01	114.82± 13.34	132.52 ±13.75	79.16± 12.64	83.14± 13.20

Annotate: with ★ P＜0.01 relatively before the treatment: with placebo group relatively ^*P＜0.01.

The clinical total effects of table 9 is (routine number) relatively

Curative effect	The example number	The basic recovery	Produce effects	Effectively	Invalid	Total effective rate	The P value
								Medicine group placebo group of the present invention	75 75	5(6.67) 0(0)	46(61.33) 2(2.67)	20(26.67) 9(12.00)	4(5.33) 64(85.33)	71(94.67) 11(14.67)	＜ 0.001

To sum up with described, it is few, simple for production, cheap that medicine of the present invention has flavour of a drug, determined curative effect, and onset is quick.It is few that medicine production method of the present invention has loss of effective components, and the purity height is simple to operate.

4. the specific embodiment

Embodiment 1

Take by weighing raw material by following proportioning:

Radix Cynanchi Paniculati 1500g Radix Angelicae Dahuricae 1000g Rhizoma Et Radix Notopterygii 1000g

Production method is as follows:

Get Radix Cynanchi Paniculati, Radix Angelicae Dahuricae, the Rhizoma Et Radix Notopterygii oven dry is crushed to 120 order fine powders, adds 30% sodium chloride solution 75000ml, distillation reclaim distillate 3500ml, concentrate and be settled to 4.5g crude drug/ml, add solubilizing agent, the sterilization bottling is standby.

Usage and consumption: adopt the administration of nasal-cavity administration mode, at rayon balls top plug nose, right nose is filled in the left side headache with medicine liquid droplet, the left nose of right side headache plug, and the left and right sides nose of having a headache entirely is used alternatingly, each 30min.Every day four times, each 0.25ml.30 days is a course of treatment.Can give medicine during the headache outbreak temporarily.

Embodiment 2

Take by weighing raw material by following proportioning:

Radix Cynanchi Paniculati 2200g Radix Angelicae Dahuricae 800g Rhizoma Et Radix Notopterygii 700g

Get Radix Cynanchi Paniculati, the Radix Angelicae Dahuricae, the Rhizoma Et Radix Notopterygii oven dry is crushed to 120 order fine powders, adds 30% sodium chloride solution 75000ml, distillation reclaim distillate 3500ml, concentrate and be settled to 3.7g crude drug/ml, add solubilizing agent, the sterilization bottling is standby.

Usage and consumption: adopt the administration of nasal-cavity administration mode, at rayon balls top plug nose, right nose is filled in the left side headache with medicine liquid droplet, the left nose of right side headache plug, and the left and right sides nose of having a headache entirely is used alternatingly, each 30min.Every day four times, each 0.25ml.30 days is a course of treatment.Can give medicine during the headache outbreak temporarily.

Embodiment 3

Take by weighing raw material by following proportioning:

Radix Cynanchi Paniculati 1000g root of Dahurian angelica 500g Rhizoma Et Radix Notopterygii 500g

Get Radix Cynanchi Paniculati, the Radix Angelicae Dahuricae, the Rhizoma Et Radix Notopterygii oven dry is crushed to 120 order fine powders, adds an amount of dextrin and adjuvant, makes the 2100g granule, pack, 7g/ bag.

Usage and consumption: oral, each one bag, every day three times.

Embodiment 4

Take by weighing raw material by following proportioning:

Radix Cynanchi Paniculati 2500g Radix Angelicae Dahuricae 2000g Rhizoma Et Radix Notopterygii 2000g

Get Radix Cynanchi Paniculati, the Radix Angelicae Dahuricae, the Rhizoma Et Radix Notopterygii oven dry is crushed to 120 order fine powders, adds 30% sodium chloride solution 100000ml, distillation reclaim distillate 50000ml, add appropriate amount of starch and adjuvant after concentrating, tabletting is made 1500, the 0.4g/ sheet.

Usage and consumption: oral, each 3-5 sheet, every day three times.

Claims (6)

1. treat migrainous medicine for one kind, it is characterized in that: it is the medicament of being made by the following weight proportion raw material

5～20 parts of 5～20 portions of Rhizoma Et Radix Notopterygiis of 10～25 parts of Radixs Angelicae Dahuricae of Radix Cynanchi Paniculati.

2. the migrainous medicine of treatment according to claim 1, it is characterized in that: the weight proportion of described raw material is

8～15 parts of 8～15 portions of Rhizoma Et Radix Notopterygiis of 12～20 parts of Radixs Angelicae Dahuricae of Radix Cynanchi Paniculati.

3. the migrainous medicine of treatment according to claim 1, it is characterized in that: the weight proportion of described raw material is

10 parts of 10 portions of Rhizoma Et Radix Notopterygiis of 15 parts of Radixs Angelicae Dahuricae of Radix Cynanchi Paniculati.

4. according to claim 1, the migrainous medicine of 2 or 3 described treatments, it is characterized in that: said medicament is a said dosage form on any pharmaceutics.

5. the migrainous medicine of treatment according to claim 4, it is characterized in that: said medicament is a nasal drop.

6. the preparation method of the migrainous medicine of the described treatment of claim 5 is characterized in that: get Radix Cynanchi Paniculati, the Radix Angelicae Dahuricae, Rhizoma Et Radix Notopterygii and pulverize, add 30% sodium chloride solution, distillation reclaim distillate, concentrated standardize solution adds solubilizing agent, the sterilization bottling.