CN104258284A

CN104258284A - Oral preparation for cerebral apoplexy and preparation method thereof

Info

Publication number: CN104258284A
Application number: CN201410508076.5A
Authority: CN
Inventors: 苏雨行
Original assignee: Individual
Current assignee: Individual
Priority date: 2014-09-22
Filing date: 2014-09-22
Publication date: 2015-01-07

Abstract

The invention belongs to the technical field of medicines and discloses an oral preparation for cerebral apoplexy and a preparation method thereof. The oral preparation is prepared from the following raw materials in parts by weight: 30 parts of ginseng, 30 parts of ginkgo leaf, 30 parts of amomum tsao-ko, 25 parts of herba epimedii, 25 parts of fructus forsythiae, 25 parts of gastrodia elata, 22 parts of myrrh, 22 parts of prepared rehmannia root, 22 parts of frankincense, 22 parts of spina date seeds, 20 parts of root of common peony, 20 parts of rhizoma calami, 20 parts of trichosanthes kirilowii Maxim, 18 parts of acanthopanax, 18 parts of Radix Ophiopogonis, 18 parts of folia perillae acutae, 17 parts of ligusticum wallichii, 17 parts of salvia miltiorrhiza, 15 parts of semen raphani, 15 parts of gynostemma pentaphylla, 10 parts of gomphrena globosa, 10 parts of radix curcumae, 10 parts of angelica sinensis, 8 parts of Eucommia ulmoides, 8 parts of Astragalus, 5 parts of Poria cocos and 5 parts of cortex albiziae. The medicines are combined with one another and bring out the best in each other, and the oral preparation is fast in effectiveness in ischaemic cerebral apoplexy and wide in application prospects.

Description

For the oral formulations and preparation method thereof of apoplexy

Technical field

The invention belongs to technical field of pharmaceuticals, concrete, relate to a kind of oral formulations for apoplexy and preparation method thereof.

Background technology

Apoplexy is a kind of cerebral blood circulation obstacle disease of unexpected onset.Be cerebrovas-cularaccident again.Refer to the patient at cerebrovascular disease, because various risk factor causes internal artery narrow, inaccessible or break, and cause acute brain disturbance of blood circulation, clinical signs is the sings and symptoms of transient or permanent disordered brain function, is a kind of acute illness caused by the angiopathy to brain pumping blood.Apoplexy has become the first disease causing human death's reason, according to World Health Organization's data, within every two seconds, just has a patient to occur, has become the formidable enemy of human health.On May 4th, 2013, " Chinese apoplexy conference and national cardiovascular and cerebrovascular disease forum " Meeting Held.Member of Chinese Academy of Engineering, the apoplexy examination of national health State Family Planning Commission and pre-preventing engineering committee deputy director king Gansu Province moral, issue in plenary lecture: national medical reform key special subjects " high risk population of stroke examination and intervention project " interim data, China's apoplexy standardized prevalence is about 1.82%, and the crowd suffering from apoplexy for more than 40 years old reaches 1,036 ten thousand people.Wherein, hypertension is ranked patients with cerebral apoplexy and to be occurred together risk factor first place.Report data shows, and patients with cerebral apoplexy accounts for 50% in less than 65 years old, shows that China's apoplexy rejuvenation situation is serious.In same conference, the vice-chairmen of the NPC Standing Committee, the apoplexy examination of health State Family Planning Commission and prevention and cure project committee director Chen Zhu, emphasize in opening speech: " prevention and control of the chronic diseases such as cerebrovascular are treatment problem, preventive management problem especially ".Should " play Government-Leading effect, transfer whole society's wide participation ", its health to the mankind and the harm to society are down to minimum.

Mainly angularly carry out from neuroprotective, anticoagulant, thrombolytic, increase blood flow and blood pressure lowering for apoplexy at present; conventional apoplexy chemotherapeutic agent comprises: 1) thrombolytic class medicine; 2) antiplatelet drug; 3) anticoagulant, 4) neurocyte protection medicine etc.But these medicines most all can only for apoplexy carry out in a certain respect extenuate and or treatment, therapeutical effect is single, and effect is undesirable, and there is many untoward reaction.Such as, conventional thromboembolism treatment drug entities plasminogen activators (tPA), although can thrombus rapidly, but the neuronal damage that can not improve because ischemia causes, the serious adverse reactions such as there is destruction blood-CSF barrier, increase bleeding risk, aggravation excititoxic and it is constantly in the news, the problems referred to above are also thrombolytic class medicine ubiquitous defects when Clinical practice.

From traditional Chinese medical science angle understanding, " blood of the five internal organs elite, all can in this for cephal highness, the gas of six internal organs Chhnang ".(bright Li Zhongzi " Required Readings for Medical Professionals "), physiology, the pathology of head are all relevant with the vital organs of the human body.If internal organs generation pathological changes or vigor decline, the essence of all marrows can not on note in brain, then can " deficiency of marrow-reservoir ", and cause " manner is on the decline ", then head illness grows thickly (" Plain Questions arteries and veins wants precise and tiny opinion ").Apoplexy is head illness, and " Plain Questions the five internal organs generate a section " points out " the headache disorder of head ", is the pathological changes that mankind's highest portion position occurs; Its cause of disease mostly is " deficiency in the lower and excess in the upper ".Be bottom vital organs of the human body generation pathological changes or deterioration and the head venation that causes disorderly inverse or obstructed caused by.Lee stile of the Ming Dynasty points out in " Elementary Medicine ": " sea of brain person marrow, all marrows all belong to brain ", and human body is along vertebra " on to brain, down to tail sacrum, the road of all marrow liftings also "." a Ling Shu Miraculous Pivot or Divine Axis five kinds of disease caused by dysfunction of QI of five ZANG-organs section " illustrates its principle and mechanism, " kidney storing essence, essence raw marrow ", " spinal cord leads in brain, brain be that marrow is poly-form ".The marrow that kidney essense is given birth to is the carrier of all marrows." all marrows " that ancient book and records intermediate frequency is shown in namely is " gas of six internal organs Chhnang, the blood of the five internal organs elite ".So head illness, all relevant with the vital organs of the human body, not caused by single internal organs, exhaustive in vast as the open sea Chinese medicine and pharmacy works.From " Yellow Emperor, a legendary ruler's Plain Questions ", " Lingshu Jing, Miraculous Pivot ", " the difficult warp of Bian Que ", Huatuo's " Huatuo's Zhongzang classic " is to Zhang Zhongjing " Medical Treasures of the Golden Chamber ", and Shanxi is for Wang Shuhe Pulse Classic, and the Tang Dynasty Sun Simiao " prescriptions worth thousand gold ", all has clear and definite discussion.Offspring doctor novel viewpoint to some extent, what discussion was invented to some extent has: the Song dynasty is sternly used and recipes for Saving Lives, Xu Shuwei " ability side "; Jin Dynasty Dou Han minister in ancient times " skin infection pandect ", Liu Wansu's " interchannel six scripts "; Yuan Dynasty's ZHANG Cong-zheng " Confucian's Duties to Their Parents ", Li Gao " eastern wall ten book ", Zhu Zhenheng " danxi's experiential therapy ", Luo Qianfu " precious mirror of hygiene "; Ming Dynasty's Xu Chunfu ancient and Modern Medicine, anxiety is fought " medical science main story ", Dai Sigong " key to Diagnosis and Treatment ", Lou Ying (1332-1402 A.D) " Compendium of medicine ", king's synthetic fibre " collection of experiences of famous physicians in the Ming Dynasty ", Lee stile " Elementary Medicine ", Li Zhongzi's " Required Readings for Medical Professionals ", Xue's own " Xue's medical records ", the virtuous Wonderful Well-Tried Recipes in side, Zhang San's stannum " medical science criterion six is wanted ", Tao Hua " the typhoid fever six scripts ", Wang Kentang " Standards of Diagnosis and Treatment ", Chen Shigong " Waike Zhengzong, Orthodox Manual of External Diseases ", ZHANG Jie bin Jing-Yue Complete Works; Qing Dynasty Yu Chang " Principle and Prohibition for Medical profession ", Chen Shiduo " the secret record in stone room " etc., but prior art prescription lacks dialectical, treatment cycle is long, and suiting the medicine to the illness property is not strong, and curative effect is not obvious, even also can bring side effect to patient, increase patient suffering, from natural drug, find effective, safe drugs, become clinical treatment apoplexy important directions.

Summary of the invention

The object of the present invention is to provide a kind of oral formulations for apoplexy.Dialectical fall control be always Chinese medicine disease core reason fall, how to take into account secondary pathogenesis for main pathogenesis medication simultaneously, taking into account the treatment of general character and individual character, thus at utmost embody intension and the extension of Chinese traditional treatment disease, is a realistic problem of Chinese patent medicine compatibility.Applicant is for apoplexy stagnant heat resistance key, network damages the pathogenic characteristic of blood oozing from the body openings or subcuta neous tissue, in conjunction with a large amount of forefathers' prescription and by the research to Chinese medicine, and in conjunction with dialectical demonstration, in many ways the length of many families is collected, seek therapeutic regimen, from motherland's medical treasure-house, filter out drastically removing blood stasis and resolving static blood, the power of the spasmolytic that relieves dizziness, high fever, infantile convulsions, epilepsy, etc., dispelling cold by warming the meridian simultaneously, the medicine of recuperating depleted YANG and rescuing the patient from collapse, by theory of Chinese medical science prescription, skim the cream off milk, the Chinese medicine preparation for apoplexy of the present invention is meticulously mixed with in conjunction with Traditional Chinese Medicine technology, relative to Western medicine, Chinese medicine of the present invention is rapid-action, effect is strong, short treating period, safety is high, without obvious toxic-side effects.All medicines share, and bring out the best in each other, and play that removing heat from blood leads to the stasis of blood, the merit of eliminating pathogenic factor for supporting vital QI improves cranium brain microcirculation altogether, and protection cerebral tissue, effectively blocks the pathological lesion of secondary.

For realizing the object of the invention, the technical solution used in the present invention is as follows:

For an oral formulations for apoplexy, it is prepared by the raw material of following weight parts and obtains:

Radix Ginseng 30 parts, Folium Ginkgo 30 parts, Fructus Tsaoko 30 parts, Herba Epimedii 25 parts, Fructus Forsythiae 25 parts,

25 parts, Rhizoma Gastrodiae, Myrrha 22 parts, Radix Rehmanniae Preparata 22 parts, Olibanum 22 parts, Semen Ziziphi Spinosae 22 parts,

Radix Paeoniae Rubra 20 parts, Rhizoma Acori Calami 20 parts, Fructus Trichosanthis 20 parts, Radix Et Caulis Acanthopanacis Senticosi 18 parts, Radix Ophiopogonis 18 parts,

Folium Perillae 18 parts, Rhizoma Chuanxiong 17 parts, Radix Salviae Miltiorrhizae 17 parts, Semen Raphani 15 parts, Herb Gynostemmae Pentaphylli 15 parts,

Flos Gomphrenae 10 parts, Radix Curcumae 10 parts, Radix Angelicae Sinensis 10 parts, the Cortex Eucommiae 8 parts, the Radix Astragali 8 parts,

5 parts, Poria, Cortex Albiziae 5 parts.

Pharmaceutical composition its preparation method of the present invention is: the crude drug mix homogeneously getting above-mentioned parts by weight, and prepare capsule, concrete operations are:

1) each crude drug is taken, for subsequent use;

2) get Radix Ginseng, Myrrha, Radix Rehmanniae Preparata, Olibanum, Semen Ziziphi Spinosae, Radix Paeoniae Rubra, Rhizoma Acori Calami, Radix Curcumae, Radix Angelicae Sinensis, the Cortex Eucommiae, the Radix Astragali,

The water intense fire that Poria, Cortex Albiziae add 3 times of weight boils, then slow fire boiling 1 hour, collecting by filtration filtrate and filtering residue; In filtering residue, add water, not have filtering residue to be as the criterion, intense fire boiled, then slow fire boiling 1 hour, collecting by filtration filtrate; Merge above-mentioned twice filtrate, after cooling, filtrate is condensed into paste, is ground into Powdered after oven dry, is complex A;

3) get residual components and add 70% soak with ethanol 2 hours, extract twice, each 1 hour, merge extractive liquid, filter, be condensed into paste, be ground into Powdered after oven dry, crushed after being dried, obtain complex B;

4) by complex A, complex B mixing and stirring, sterilization obtains capsule product.

Instructions of taking: each oral 1g, three times on the one.

The component of medicine of the present invention all adopts natural raw material of Chinese medicine, and its preparation is easy, and medicine source is extensive, with low cost, it follows the prescriptions principle of the traditional Chinese medical science, and all medicines share, bring out the best in each other, invention formulation dose is little, and effective ingredient is easy to release, absorb fast, bioavailability is high, and drug effect is given full play to, through clinical practice checking, it is reliably evident in efficacy, mild in medicine property and, there is not toxic and side effects, have a extensive future.

Detailed description of the invention

Embodiment 1

For an oral formulations for apoplexy, it is prepared by the raw material of following weight proportioning and obtains:

5 parts, Poria, Cortex Albiziae 5 parts.

1) each crude drug is taken, for subsequent use;

Embodiment 2

Experiment of Zoology

Healthy Kunming Strains of Mouse 40, male and female half and half, body weight is 18.5 ± 2.0g, 40 mices is divided into two groups at random, male and female half and half, and wherein 20 as matched group, fills with ordinary water; Other 20 mices give embodiment 1 medicine, and mice carries out acute toxicity testing and shows in application: compare with matched group, after administration, mice has no notable difference, experiment Continuous Observation two weeks, mouse systemic situation, ingest, drink water, body weight growth is all normal.After the administration same day and administration in two weeks, have no animal dead, point out this medicine acute toxicity low, clinical drug safety.

After ligation bilateral common carotid arteries causes cerebral ischemia, the impact of mouse survival time is tested:

The acute cerebral ischemia mouse model of bilateral common carotid arteries and vagus nerve caused by ligature is adopted to investigate the effect of pharmaceutical composition, described mouse model modeling method is: 0.5h after the last gastric infusion of mice, after the anesthesia of shallow table being carried out to it with ether, rapid ligation bilateral common carotid arteries and vagus nerve, observe the mouse survival time.This animal model is the common model of acute cerebral ischemia anoxia; and one of the pathological effect of acute cerebral ischemia anoxia apoplexy just; therefore; time-to-live after this animal model administration tentatively can reflect the protective effect of this medicine to cerebral ischemia, anoxia, can as the screening index of apoplexy medicine.Experimental result shows that medicine of the present invention causes mice to bilateral ligation and lacks the significant prolongation compared with model group of the time-to-live after acute cerebral ischemia.

Laboratory animal: kunming mice (KM mice), contrast medicine: Tanakan;

Get kunming mice 60, male and female half and half, be divided into following 3 groups according to body weight and sex:

Negative control group: only give the normal saline calculating gained volume by 20ml/kg Mouse Weight;

Positive controls: give Tanakan 20mg/kg;

Medicine group of the present invention: give Chinese medicine composition 20mg/kg prepared by embodiment 1; Concrete outcome is in table 1:

Table 1

Group	Sample	Dosage (mg/kg)	Time-to-live (s)
				Negative control	20	Same volume normal saline	121.7±27.3
Positive control	20	20	183.3±30.5
				Medicine group of the present invention	20	20	197.5±33.7

Shown by upper table result, compared with negative control group, the time-to-live of the obvious lengthening model mice of medicine group energy of the present invention, illustrate that this pharmaceutical composition has good protective effect for cerebral ischemia, anoxia.

Embodiment 3

Clinical data

Physical data patient 120 example is all inpatient, and diagnosis meets nineteen ninety-five the 4th national cerebrovascular academic conference revision " diagnostic point of all kinds of cerebrovascular disease " diagnostic criteria.Patient is divided into treatment group and matched group at random, treatment group 60 example, man 37 example, female 23 example; 47 ~ 81 years old age, course of disease 2h ~ 3 year; Matched group 60 example, man 36 example, female 24 example; 46 ~ 79 years old age, course of disease 3h ~ 3 year.Two groups at sex, age, course of disease no significant difference (P > 0.05).

About the diagnosis basis of apoplexy is formulated in " traditional Chinese medicine industry standard one Chinese medical disease Standardization of diagnosis and curative effect " that diagnostic criteria reference State Administration of Traditional Chinese Medicine issues.

Exclusion standard is cerebral hemorrhage patient 1.; 2. serious symptom or cerebral hernia former; 3. obnubilation person; 4. the functional defect person such as severe hypertension and the heart, liver, kidney is merged; 5. acute or unmanageable disease is suffered from.

Therapeutic Method: treatment group: take oral formulations prepared by embodiment 1, every day three times, each 1g; Matched group: ozagrel sodium injection 80ml adds 0.9% sodium chloride injection 250ml, and hetastarch 500ml adds sodium chloride injection 500ml, intravenous drip, 1 time/d.Two groups equal 7 days be a course for the treatment of.

Criterion of therapeutical effect, with reference to " clinical neurologic deficit of stroke patients degree standards of grading (1995) ", is almost recovered: the scoring of functional impairment degree reduces 91%-100%, and disability degree is 0 grade; Effective: the scoring of functional impairment degree reduces 46%-90%, and disability degree is 1-3 level; Effective: the scoring of functional impairment degree reduces 18%-45%; Invalid: functional impairment scoring is lower than 18% or dead.

Before and after therapeutic outcome two groups treatment, comparitive study is in table 1.Difference all has significant (P < 0.05)

Table 1 Clinical efficacy comparison

Conclusion: experimental group is matched group significant difference comparatively.

What more than enumerate is only best specific embodiment of the present invention.Obviously, the invention is not restricted to above embodiment, many distortion can also be had.All distortion that those of ordinary skill in the art can directly derive from content disclosed by the invention or associate, all should think protection scope of the present invention.

Claims

1. for an oral formulations for apoplexy, it is characterized in that, described preparation is prepared by the raw material of following weight parts and obtains:

5 parts, Poria, Cortex Albiziae 5 parts.

2. oral formulations according to claim 1, is characterized in that, described preparation is prepared as follows and forms:

1) each raw material is taken according to weight portion, for subsequent use;

Poria and Cortex Albiziae, the water intense fire adding 3 times of weight boils, then slow fire boiling 1 hour, collecting by filtration filtrate and filtering residue; In filtering residue, add water, not have filtering residue to be as the criterion, intense fire boiled, then slow fire boiling 1 hour, collecting by filtration filtrate; Merge above-mentioned twice filtrate, after cooling, filtrate is condensed into paste, is ground into Powdered after oven dry, is complex A;

3) get surplus stock, add 70% soak with ethanol 2 hours, extract twice, each 1 hour, merge extractive liquid, filter, be condensed into paste, be ground into Powdered after oven dry, crushed after being dried, obtain complex B;

4) by complex A, complex B mixing and stirring, sterilization and get final product.

3. the oral formulations according to claim 1-2 is used for Treatment of Cerebral Stroke.