CN102579989B - Flunarizine hydrochloride and preparation process thereof - Google Patents
Flunarizine hydrochloride and preparation process thereof Download PDFInfo
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Abstract
The invention relates to compound flunarizine hydrochloride and a preparation process thereof. The compound flunarizine hydrochloride is prepared from the following raw materials in part by weight: 0.7 part of flunarizine hydrochloride, 25 parts of root of red-rooted salvia, 20 parts of common burreed rhizome, 18 parts of zedoary, 15 parts of tall gastrodia tuber and 10 parts of glossy privet fruit, starch live edible cellulose serving as a pharmaceutic adjuvant are added according to the conventional pharmaceutic method to prepare formulations such as capsules, tablets, granules and the like. The compound flunarizine hydrochloride medicinal composition addresses both root causes and symptoms on epilepsy, is non-toxic and harmless to human bodies, does not have side effect, is low in costand easy and convenient to prepare, and has a bright application prospect.
Description
Technical field
The invention belongs to medical technical field, be specifically related to treat the Chinese-western medicine preparation of epilepsy, is the auxilliary application of medicine in epilepsy of making based on Western medicine flunarizine hydrochloride, Chinese herbal medicine particularly.
Background technology
Epilepsy (Epilepsy, EP) be since the temporary excessive high-frequency discharge of cerebral neuron group caused a kind of repeatedly, of short duration ictal functional disorders of brain syndrome.Show as and break out, stop automatically, the obstacle of recurrent motion, sensation, spirit and consciousness aspect is chronic convulsibility disease.According to incompletely statistics, the present epilepsy invasion rate of China is about 6 ‰, and the patient nearly 9,000,000, and annual 450000 the New Development patient of also having an appointment.Most studies finds that male's epilepsy invasion rate is 57.1%, is higher than women 42.7% sickness rate, and the rural area sickness rate is higher than the cities and towns sickness rate.Disclose according to the academic meeting of the 5th epileptics in the whole nation, among the epilepsy crowd of China, the patient more than 40% never carried out treatment, and what 35% patient accepted is irregular treatment, and its disability rate and mortality rate are also higher, have become the problem that is worth society to pay attention to.
Through correct diagnosis, typing and appropriately use antiepileptic (AEDs), there is patient's outbreak of 70%～80% can be controlled, but still has the patient's curative effect of medication about 30% not good enough, outbreak is difficult to control, becomes intractable epilepsy.Intractable epilepsy is to compare stubborn problem clinically, does not still have ideal method at present.Flunarizine hydrochloride is the research hot issue as the interpolation treatment of intractable epilepsy in recent years, its possible mechanism of action is as follows: 1. antagonism multidrug resistance transporter multidrug resistance albumen, the P-glycoprotein, the concentration of AEDs is improved the overexpression of MDR gene in the raising brain; Intracellular calcium overload when 2. blocking the depolarization of epilepsy affected area neuron prevents the neuronic paroxysmal depolarization of epilepsy affected area change, epilepsy discharge and epilepsy; 3. can alleviate the neuronic degeneration necrosis that calcium overload causes, expansion of cerebral vascular improves the cerebral tissue circulation, and hypoxic-ischemic and metabolite are to neuronic damage when alleviating epilepsy.Flunarizine hydrochloride is a kind of selectivity Ca2+ antagonist as the diphenyl piperazine derivative, can enter the cerebral artery vessel smooth muscle cell by selectivity inhibition Ca2+, removes vasospasm, and blood flow increasing improves the supply of brain oxygen, and does not influence heart rate.Zoopery proves; accumulation and the overload of the interior Ca2+ of cell when flunarizine hydrochloride can be blocked the depolarization of epilepsy affected area brain cell; thereby have the depolarization change that prevents epilepsy affected area brain cell and an epileptic discharge of brain cell; and protection cerebral tissue function and cerebrovascular endothelial cell function are arranged, improve the sanguimotor function of brain and inner ear labyrinth.
Yet, the patient is in taking medicine for a long time, show toxicity in various degree, can have influence on the function of a plurality of systems such as nervus centralis, breathing, digestion, hemopoietic, urinary system, and for intractable epilepsy, cure rate is still not remarkable, and with regard to its obtained recent, late result, the result is difficult to satisfactory.
The traditional Chinese medical science thinks that the pathological change of insane pain is the parent suddenly frightened, causes mechanism of qi contrary disorderly first, causes smart the wound first and deficiency of the kidney, so-called " probably then essence but ", and it is unusual that fetal development is produced, and auxilliary card takes place in the birth back, and this is due to the congenital factors.Epilepsy syndrome causes visceral dysfunction mainly due to terrified and intemperance of taking food due to the acquired disposition: suddenly suffering intense fright and dread, cause mechanism of qi disorderly contrary, " excessive fear leading to sinking of kidney-QI ", " excessive fright leading to disturbance of QI ", and then damage internal organs, impaired as Liver and kidney, can make hepatic and renal YIN deficiency, give birth to hot air wind producing, the impaired then strong mistake department that transports of taste, expectorant is turbid cohesion, and one meets inducement, scurries brain god on the wind-fire and phlegm-heat, hoodwink the clear key of the mind, and send out epilepsy.If feelings will is not relaxed, overfatigue, depression of liver-QI, liver-wind folder expectorant superinverse, inaccessible thinking, the meridians that are jammed also can be sent out and are epilepsy.In addition, because after the brain wound, mind is disorderly contrary, qi and blood stagnation, channels is got along well, and also can send out to be epilepsy.Epilepsy and kidney,liver,spleen three dirty relations are the closest, and pathogenesis conversion and wind, expectorant, the stasis of blood are relevant, and it is the most important to haunt with the expectorant heresy especially.The Chinese traditional treatment epilepsy is by adjusting human body yin-yang balancing and function to recover the allomeric function state of body, according to the etiology and pathogenesis difference, and method for the treatment of rule for the treatment of difference, dialectical executing controlled.The Chinese medicine epilepsy has advantages such as the medicine source is wide, method is various, toxic and side effects is little, avoids the Western medicine antuepileptic to cause side effect such as drowsiness, cognitive dysfunction, hemopoietic system inhibition; Some Chinese medicine also has dual regulation, has the whole body of adjusting function, the effect of raise immunity.Therefore the Chinese medicine and western medicine compound drug of seeking a kind of high-efficiency low-toxicity, treating both the principal and secondary aspects of a disease is the technical barrier of pendulum in face of medical circle.
Summary of the invention
The purpose of this invention is to provide that a kind for the treatment of both the principal and secondary aspects of a disease, side effect are little, safe ready, cheap compound hydrochloric acid flunarizine medicine.Its objective is that it is not remarkable to overcome Western medicine flunarizine hydrochloride effect in order to solve the intractable epilepsy for the treatment of, and easily knock-on, the problem that toxic and side effects is big reaches the purpose for the treatment of both the principal and secondary aspects of a disease.
The present application people is according to forefathers' experience and oneself medical practice for many years, by the research to Chinese medicine, and in conjunction with dialectical demonstration, in many ways collect the length of many families, seek therapeutic regimen, from motherland's medical treasure-house, filter out the natural Chinese medicine of benefiting QI for activating blood circulation, tranquillizing and allaying excitement, by the theory of Chinese medical science prescription, be mixed with the compound hydrochloric acid flunarizine pharmaceutical composition for the treatment of epilepsy of the present invention meticulously in conjunction with traditional lunar physics technique, intractable epilepsy there is the effect of taking stopgap measures and effecting a permanent cure.
For achieving the above object, the technical solution used in the present invention is as follows:
A kind of compound hydrochloric acid flunarizine pharmaceutical composition is characterized in that it is got by following weight proportioning feedstock production,
Flunarizine hydrochloride 0.5-1 part, Radix Salviae Miltiorrhizae 20-30 part, rhizoma sparganic 20-30 part, Rhizoma Curcumae 10-25 part, Rhizoma Gastrodiae 10-15 part, Fructus Ligustri Lucidi 8-10 part.
Preferably, described raw material weight proportioning is:
0.7 part of flunarizine hydrochloride, 25 parts of Radix Salviae Miltiorrhizaes, 20 parts of rhizoma sparganic, 18 parts of Rhizoma Curcumae, 15 parts in Rhizoma Gastrodiae, 10 parts of Fructus Ligustri Lucidi.
Wherein said flunarizine hydrochloride can commercially availablely be bought, and the preferred for preparation method is:
1, charge ratio
2, production technology
2, the preparation of 1 pair of fluorobenzene chloromethanes: the retort of 300L is dried slightly, zinc chloride and concentrated hydrochloric acid are added, stir, nature heat release dissolving, complete molten after, add two fluorophenyl methanols, heating, the control temperature is at 60-70 ℃, reacted 1 hour, and be cooled to 30 ℃, add methylbenzene extraction 3 times, 170-180 ℃ of fraction collected in decompression, gets two fluorobenzene chloromethanes 30.3kg.Yield is 84.7%.
2,2 flunarizine hydrochloride is synthetic: cinepazide, two fluorobenzene chloromethanes, triethylamine, toluene are added retort successively, and stirring and refluxing to 110 ℃ continues reaction 6 hours, add water 50kg, dissolving crystallized, stir, separate, remove water layer, add water 40kg again, transfer PH to neutral with hydrochloric acid, branch vibration layer is transferred PH to 1-2 with hydrochloric acid, solidify, cold preservation, next day sucking filtration, the dry crude product 58kg that gets, yield is 95.7%.
2,3 is refining: crude product: dehydrated alcohol: active carbon=58: 200: 2 (weight ratio)
Crude product, dehydrated alcohol are added retort, be heated with stirring to moltenly entirely, added activated carbon decolorizing 30 minutes, filter, below the filtrate crystallization, cold preservation to 5 ℃, centrifugal, dehydrated alcohol is washed 2 times, dry flunarizine hydrochloride 47kg.Yield is 81%.
Pharmaceutical composition of the present invention comprises the pharmaceutical preparation for the conjoint therapy of gastrointestinal administration, as bag film-coat, tablet, capsule.If not otherwise specified, then these preparations are to be prepared with method well known in the art.For example prepare with conventional mixing, granulation, tabletting, coating, dissolving or freeze-drying.
When the compositions of preparation peroral dosage form administration, can use conventional media, for example water, alcohols, glycols, oils; Preparation oral solid formulation class such as powder, tablet, drop pill, capsule, operable carrier, as starch, saccharide, microcrystalline Cellulose, magnesium stearate, cross-linked pvp, micropowder silica gel, diluent, granulating agent, lubricant, binding agent, disintegrating agent etc.
Preferably, described compound hydrochloric acid flunarizine preparation of pharmaceutical compositions method is: get flunarizine hydrochloride 0.7g, Radix Salviae Miltiorrhizae 25g, rhizoma sparganic 20g, Rhizoma Curcumae 18g, Rhizoma Gastrodiae 15g, Fructus Ligustri Lucidi 10g, make capsule through pulverizing according to a conventional method, every 0.5g is finished product through being up to the standards.
Technical solutions according to the invention are on the clinical experience basis of Chinese traditional treatment epilepsy, in conjunction with the compound preparation with the Chinese medicine and western medicine combination of modern pharmacy achievement development.With Chinese medicine and Western medicine combination effectively, have suppressing the hyperactive liver to arrest the wind syndrome, mind tranquilizing and the heart calming effect very doughtily, can improve symptom rapidly, stop course of disease development, epilepsy there is the effect of healing, overcomes the onset of prior art Chinese medicine and reach shortcomings such as toxicity is big slowly, reach the purpose for the treatment of both the principal and secondary aspects of a disease, recommend take above-mentioned compound hydrochloric acid flunarizine pharmaceutical composition once a day every day, take evening, one time one, one month is a course for the treatment of.
Compound hydrochloric acid flunarizine pharmaceutical composition advantage of the present invention is as follows:
1 the present invention adopts the preparation flunarizine hydrochloride of improving one's methods, and its yield is higher.
2 full sides cooperate appropriate epilepsy pathogenesis, and prescription is reasonable, and drug effect is deeply lasting in order, medicine letter and power is special;
3 the present invention have obtained desirable therapeutic effect by the choose reasonable to medicine components, proportioning, have both met state-promulgated pharmacopoeia to the requirement of relevant drug dose, can guarantee excellent curative, non-evident effect again.
The specific embodiment
Embodiment 1
A kind of compound hydrochloric acid flunarizine pharmaceutical composition is characterized in that it gets 0.7 part of flunarizine hydrochloride, 25 parts of Radix Salviae Miltiorrhizaes, 20 parts of rhizoma sparganic, 18 parts of Rhizoma Curcumae, 15 parts in Rhizoma Gastrodiae, 10 parts of Fructus Ligustri Lucidi by following weight proportioning feedstock production.
Wherein said flunarizine hydrochloride can commercially availablely be bought, and the preferred for preparation method is:
1, charge ratio
2, production technology
2, the preparation of 1 pair of fluorobenzene chloromethanes: the retort of 300L is dried slightly, zinc chloride and concentrated hydrochloric acid are added, stir, nature heat release dissolving, complete molten after, add two fluorophenyl methanols, heating, the control temperature is at 60-70 ℃, reacted 1 hour, and be cooled to 30 ℃, add methylbenzene extraction 3 times, 170-180 ℃ of fraction collected in decompression, gets two fluorobenzene chloromethanes 30.3kg.Yield is 84.7%.
2,2 flunarizine hydrochloride is synthetic: cinepazide, two fluorobenzene chloromethanes, triethylamine, toluene are added retort successively, and stirring and refluxing to 110 ℃ continues reaction 6 hours, add water 50kg, dissolving crystallized, stir, separate, remove water layer, add water 40kg again, transfer PH to neutral with hydrochloric acid, branch vibration layer is transferred PH to 1-2 with hydrochloric acid, solidify, cold preservation, next day sucking filtration, the dry crude product 58kg that gets, yield is 95.7%.
2,3 is refining: crude product: dehydrated alcohol: active carbon=58: 200: 2 (weight ratio)
Crude product, dehydrated alcohol are added retort, be heated with stirring to moltenly entirely, added activated carbon decolorizing 30 minutes, filter, below the filtrate crystallization, cold preservation to 5 ℃, centrifugal, dehydrated alcohol is washed 2 times, dry flunarizine hydrochloride 47kg.Yield is 81%.
Above-mentioned composition added as the starch living food according to common pharmaceutical methods make dosage forms such as capsule, tablet, granule after with the cellulose pharmaceutic adjuvant.
Preferably, described compound hydrochloric acid flunarizine preparation of pharmaceutical compositions method is: get flunarizine hydrochloride 0.7g, Radix Salviae Miltiorrhizae 25g, rhizoma sparganic 20g, Rhizoma Curcumae 18g, Rhizoma Gastrodiae 15g, Fructus Ligustri Lucidi 10g, make capsule through pulverizing according to a conventional method, every 0.5g is finished product through being up to the standards.
Adopt the non-clinical study method to test, bring out mice and rat with strychnine and pentylenetetrazole, maximal electroshock in the pharmacological evaluation and faint from fear and act as clinical petit mal epilepsy and grand mal model, screen epilepsy petit mal and grand mal medicine.1OOV alternating current energising 0.3s stimulates mice ears (use the normal saline moistening), selects to stimulating the back the tetanic but not dead mice of pair hind legs, male and female dual-purpose to occur.Record mice electrofit incidence rate is observed the epilepsy capsule causes frightened effect to maximal electroshock influence.Gastric infusion is observed maximal electroshock and is caused mice convulsion rate and tubocurarine intracerebroventricular injection and cause the anticonvulsant action that rat convulsions rate and pentylenetetrazole inducing mouse are fainted from fear.Can reduce significantly behind the compound hydrochloric acid flunarizine gastric infusion of the present invention as a result that maximal electroshock causes the mice convulsion rate and tubocurarine causes rat convulsions rate, the convulsions rate reduces to 62% and 15% respectively; Can obviously reduce the intraperitoneal perfusion strychnine and cause mice convulsion rate (the convulsions rate reduces to 10%), can obviously prolong pentylenetetrazole and cause the mice convulsion induction period.Conclusion shows that compound hydrochloric acid flunarizine of the present invention has tangible anticonvulsant action.
Embodiment 2
Clinical data
Choose outpatient's totally 101 examples with complete case.Male 52 examples wherein, women 49 examples; 21～61 years old age, comprehensive grand mal 46 examples wherein, myoclonic seizure 24 examples, complex partial seizures 16 examples, simple partial seizures 5 examples, petit mal 5 examples, Lennox-Gastaut syndrome 3 examples, other 2 examples, great majority are taken two kinds and two or more medicine, are phenytoin Sodium, sodium valproate, carbamazepine, phenobarbital, clonazepam, topiramate.Patient is according to concrete condition equilibriums such as sex, age, the state of an illness, medicining conditions, be divided into 2 groups at random, and 36 examples are organized in treatment, matched group 35 examples, positive controls 30 examples.
The epilepsy diagnostic criteria
Tcm syndrome diagnostic criteria: (1) wind-phlegm impatency card: tendencys such as uncomfortable in chest, dizzy are arranged before the outbreak; Dusk is pounced on gnathospasma, two fixed staring upward, tic of the limbs, slobbering suddenly during outbreak; After waking up giddy is arranged still, refreshing tired, tongue is greasy in vain, stringy and rolling pulse.(2) excess syndrome of stroke in the phlegm-fire: at ordinary times or irritable before the outbreak, headache and insomnia; Go into a coma during outbreak, twitch doubly very bitter taste and dryness in the mouth, conjunctival congestion constipation, red tongue, yellow fur, stringy and rolling pulse number.(3) caused by liver and kidney deficiency card: outbreak is arranged during epilepsy syndrome, lethargy, Light-headedness, the hypophrenia, soreness of the waist and knees, red tongue, tongue is few, stringy and thready pulse.(4) syndrome of deficiency of both heart and spleen: epilepsy syndrome is sent out repeatly, spiritlessness and weakness, and palpitation and sleeplessness, forgetful giddy, the complexion rolling is white, lack of appetite, light red tongue, thin fur, thready pulse.(5) stagnation of QI-blood card: epilepsy syndrome is sent out repeatly, head twinge or localized pain, darkish complexion or dark and gloomy, purplish tongue or petechia is arranged, hesitant pulse.
The Western medicine diagnose standard: before (1) outbreak tendency is often arranged, show as of short duration sensory disturbance during outbreak, limbs are twitched, loss of consciousness, behavior disorder or dysautonomia, and outbreak is sanity later, and is weak all over; The lighter only has unexpected god slow-witted, pale complexion, or binocular stares, and head turns forward, and the short time namely recovers normal; (2) do not have regularly outbreak repeatedly, persistent period length does not wait, and majority namely ended to several minutes in the several seconds, and minority reached more than a few hours, and know nothing the outbreak situation back of reviving; (3) EEG (electrocardiogram) examination is unusual.
Selected and exclusion standard: the patient that makes a definite diagnosis that typical clinical performance and definite electroencephalogram evidence are arranged; Routine is taken more than a kind the line antiepileptic at its outbreak type, at least 3 months medicine times, no serious medicine side reaction, blood drug level is in effective therapeutic domain, every month, outbreak was no less than 4 times, observed at least and still can not control outbreak in 2 years, influenced daily life.Exclusion standard: incorrect because of typing, medication is unreasonable, underdosage, the time falls short of or the epilepsy that at all do not have regular treatment to cause is sent out the author repeatedly, and the sexual centre of carrying out patient with nervous system disease is arranged.
Therapeutic Method: all patients continue to take former antuepileptic sodium valproate etc., and dosage is constant.: (1) test group: the embodiment of the invention 1 compound hydrochloric acid flunarizine pharmaceutical composition 1 time/day, oral, take one every night; (2) matched group: identical medication is given and placebo treatment; (3) positive controls is taken flunarizine hydrochloride (enlightening husky Pharmaceutical), every day 5mg, two the course for the treatment of post analysis.
Curative effect determinate standard
1. curative effect index, the seizure frequency in two months observation periods for the treatment of and reduce case more than 50% than the baseline period seizure frequency; 2. safety index, expert comprehensively physical examination for the treatment of phase and department of neurology training check, and check routine blood test, hepatic and renal function, electrocardiogram; 3. eeg index, go into before the group and finish the course for the treatment of after check electroencephalogram respectively, divide highly unusual, moderate is unusual, mile abnormality and normal electroencephalogram.Attack times before with the patient is benchmark, compares with attack times behind the adding compound hydrochloric acid flunarizine pharmaceutical composition.The attack times minimizing is produce effects more than 75% after 2 months, and 50%～75% is that effectively 25%～50% is heterodyne, is invalid below 25%.
The statistical method measurement data is represented with mean ± standard deviation, relatively uses chi-square test of four-fold table between group, relatively uses paired t-test in the group.All data use SPSS10.0 software to carry out statistical analysis, and establishing P＜0.05 has statistical significance for difference.
The result is as shown in the table:
| Group | Example is inferior | Cure | Produce effects | Effectively | Heterodyne | Total effective rate |
| The treatment group | 36 | 7 | 15 | 12 | 2 | 94.4％ |
| Matched group | 35 | 0 | 9 | 15 | 11 | 68.5％ |
| Positive controls | 30 | 2 | 11 | 12 | 5 | 83.3 |
Three groups obvious effective rate is respectively: 61.1%, 25.7%, 43.3%, and total effective rate is respectively 94.4%, 68.5%, 83.3%,, have significant difference.
Embodiment 3
Exemplary embodiments
Yuan, the man, 9 years old, the patient is initial trouble epilepsy from 7 years old, and outbreak in every month does not wait for 3～5 times, because of 2 years surplus the seeking medical advice of showing effect repeatedly.It is extensive that outbreak shows as the partial seizures whole body.Successively give nitrodiazepam, sodium valproate, Lamictal, Qu Lai, phenobarbital epilepsy treatment failure.Shriek is arranged during outbreak, spit out white foams, tetany, syncope turns on two orders, and expectorant toot sound is arranged in the larynx, and urinary incontinence is namely waken up behind about 5～10min.Then bring out in case of frightening, go up the sense heating at ordinary times.Examine quarter: mind is clear, spirit still can, it is blunt slightly to react, cardiopulmonary auscultation (), the soft liver spleen of abdomen does not touch, neurologic check depletion of YANG gonosome is levied.Brain CT (one), EEG (electrocardiogram) examination has point-slow complex wave.Body of the tongue is light red, and tongue is greasy in vain, rolling pulse.Be diagnosed as intractable epilepsy, add the compound hydrochloric acid flunarizine pharmaceutical composition of embodiment 1 preparation after one month in dosage basis of invariable such as continuing to take former antuepileptic sodium valproate, than the baseline period seizure frequency improvement is arranged, in two courses for the treatment of, symptom control after treatment two courses for the treatment of is continued to strengthen in only once morbidity, and checked half a year afterwards, remain dormant and EEG (electrocardiogram) examination normal, during do not have the adverse events of obvious clinical meaning.Now fully recover, normally go to school.
Liu, woman, 31 years old.Main suit: the large and small outbreak of epilepsy 5 years.Symptom is lighter when showing effect for the first time, giddy only occurs, dark and dim eyesight, and the shake of two handss continues about 2 minutes.Just the clothes sodium valproate can be controlled outbreak.Though but still adhered to obeying sodium valproate before 3 years, can not control outbreak.After change clothes phenytoin Sodium, stable, phenobarbital etc., grand mal still will appear 3-4 time in every month, stupor, tic of the limbs occur, spit out white foams, etc. symptom, since the patient idiopathy, the various big hospital diagnosis and treatment had once repeatedly been gone, the state of an illness does not see and is clearly better that EEG (electrocardiogram) examination severe is unusual, and the discharge of epilepsy sample is arranged.Introduce by the patient, continuing to take the compound hydrochloric acid flunarizine medicine composite for curing that former antuepileptic dosage basis of invariable is added embodiment 1 preparation, in two courses for the treatment of, show effect 3 times, but symptom is lighter, continue to take two courses for the treatment of after, it is normal that electroencephalogram recovers, not recurrence is followed up a case by regular visits in drug withdrawal after three courses for the treatment of.
Above-mentioned each Chinese medicine and western medicine that the present invention adopts is made compatibility mutually, can bring into play its collaborative effect of curing the disease, having drug effect between each composition of used raw material of Chinese medicine is interweaved and mutually promotes and coordinate usefulness, through clinical verification, epilepsy there is good adjuvant treatment effect, in the applicant's medical practice for many years, the case number of curing is numerous, all obtain good effect, and with low cost, alleviate patient's burden.
The compound hydrochloric acid flunarizine pharmaceutical composition of the application's treatment epilepsy is with low cost, evident in efficacy, has broad application prospects.
Claims (2)
1. a compound hydrochloric acid flunarizine pharmaceutical composition is characterized in that it gets 0.7 part of flunarizine hydrochloride, 25 parts of Radix Salviae Miltiorrhizaes, 20 parts of rhizoma sparganic, 18 parts of Rhizoma Curcumae, 15 parts in Rhizoma Gastrodiae, 10 parts of Fructus Ligustri Lucidi by following weight proportioning feedstock production.
2. the described compound hydrochloric acid flunarizine of claim 1 pharmaceutical composition is preparing the purposes for the treatment of in the epilepsy medicine.
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Effective date of registration: 20171122 Address after: 276600 Shandong Province Economic Development Zone Linyi city Junan County Road, Huaihai Road West first Tong Ren Pharmaceutical Co. Ltd. Patentee after: Tong Ren Pharmaceutical Co., Ltd. Address before: 276600 No. 106, democracy Road, Junan County, Linyi, Shandong Patentee before: Shandong Kernel and Hall Pharmaceutical Industry Co., Ltd. |