CN103893325B - The application of Herba Hedyotidis Diffusae - Google Patents

Abstract

The invention discloses the application of Chinese medicine Herba Hedyotidis Diffusae, this application is the application of Herba Hedyotidis Diffusae as preparation treatment subarachnoid hemorrhage medicine.By animal model experiment, the present invention confirms that Herba Hedyotidis Diffusae can alleviate the degree of cerebral edema that subarachnoid hemorrhage causes; Promote the absorption of subarachnoid space remained blood; Reduce the destructiveness of blood brain barrier; Alleviate basilar artary vasospasm degree; Improve Neuroscore etc.By improving above-mentioned several clinical indices and then shielding to cerebral tissue, subarachnoid hemorrhage is had significant therapeutic effect.

Description

The application of Herba Hedyotidis Diffusae

Technical field

The present invention relates to medical art, specifically a kind of Herba Hedyotidis Diffusae is as the application of preparation treatment subarachnoid hemorrhage medicine.

Background technology

Herba Hedyotidis Diffusae is the herb of Maguireothamnus speciosus Herba Hedyotidis Diffusae, begin to be loaded in " Mingyi Bielu ", another name Herba Hedyotidis Diffusae, Serpentis needle grass, short foot spend Chinese Lobelia, Herba Turczaninowiae Fastigiatae, Radix Picriae felterrae, crane SHECAO, Herba Otteliae Alismoidis etc. in vain, it is the medical material kind that version " Chinese Pharmacopoeia " annex III in 2010 records, record in local medical material standard, be China's conventional Chinese crude drug among the people more before.It is cold in nature, bitter in the mouth, sweet, GUIXIN, liver, spleen channel, pharmacological research show this medicine have antitumor, antiinflammatory, antibacterial, strengthen the effect of immunologic function, there is effect of heat-clearing and toxic substances removing, inducing diuresis to remove edema, for acute appendicitis, furuncle toxic swelling, laryngopharynx swelling and pain, venom, damp and hot yellow cellulitis, nephritis, liver cirrhosis, early stage lymphoid tuberculosis, stomatitis, dysuria etc., having inhibitory action to pathogenic bacterium such as bacillus pyocyaneus, staphylococcus aureus, streptococcus pneumoniae, dysentery bacteriums, is the good medicine of " heat-clearing and toxic substances removing ".At present also for prevention and the auxiliary treatment of various cancer.

The BAIHUASHESHECAO ZHUSHEYE kind of current commercially available SFDA approval is as shown in table 1, and package insert is set forth its function and cured mainly and comprise: heat-clearing and toxic substances removing, inducing diuresis and reducing edema.Respiratory tract infection caused by poison, tonsillitis, pneumonia, cholecystitis, appendicitis, carbuncle furuncle abscess and post-operative infection is accumulate for damp and hot.Also can be used for the auxiliary treatment of cancer.Especially gastric cancer, the esophageal carcinoma, lymphatic cancer, breast carcinoma etc. are widely used.

And the medicine of other preparation of Herba Hedyotidis Diffusae is as shown in table 2, be the preparation containing Herba Hedyotidis Diffusae recorded in version " Chinese Pharmacopoeia " for 2010, totally ten kinds, its effect as described in table, there are no the report for the treatment of subarachnoid hemorrhage.

The BAIHUASHESHECAO ZHUSHEYE kind that table 1 SFDA ratifies

Authentication code	Approved date	Manufacturer
			The accurate word 234020595 of traditional Chinese medicines	2002-10-16	Area, Fengyang County, Anhui Science Court pharmaceutcal corporation, Ltd
The accurate word 234020606 of traditional Chinese medicines	2002-10-16	The large east Pharmaceutical Co., Ltd in Anhui
			The accurate word 222024750 of traditional Chinese medicines	2002-09-13	Jilin Longtai Pharmaceutical Co., Ltd.
The accurate word 222025029 of traditional Chinese medicines	2002-09-13	Xiuzheng Pharmaceutical Group Changchun Gaoxin Pharmaceutical Co., Ltd.
			The accurate word 222024489 of traditional Chinese medicines	2002-09-13	Jilin Province Huinan Changlong Biochemistry Medicine Co., Ltd
The accurate word 222022101 of traditional Chinese medicines	2002-08-16	Jilin Province Tonghua Zhenguo Medicine Co., Ltd
			The accurate word 222020807 of traditional Chinese medicines	2002-08-16	Jilin Province Huinan Huifa Pharmacy stock Co., Ltd
The accurate word 236020632 of traditional Chinese medicines	2002-06-21	Yujiang Pharmaceutical Factory

The preparation containing Herba Hedyotidis Diffusae is recorded in table 2 2010 version " Chinese Pharmacopoeia "

Preparation title	Record the page number	Preparation effect
			Yiganning granules	403	Air making-up and spleen enlivening, invigorating blood circulation dysentery, heat-clearing and toxic substances removing
Twin-arc twin-wire	610	Clearing away heat-damp and promoting diuresis, reduce phlegm alleviating distention in middle-JIAO, vital energy regualting and blood circulation-promoting
			HUAHONG PIAN	734	Heat-clearing and toxic substances removing, dampness leukorrhagia stopping, tired pain relieving of dispelling
HUAHONG KELI	735	Heat-clearing and toxic substances removing, dampness leukorrhagia stopping, tired pain relieving of dispelling
			Capsule with pseudo-ginseng and Chinese fanpalm seed	831	Heat-clearing and toxic substances removing, reducing swelling and alleviating pain, QI invigorating is reduced phlegm
The luxuriant GANFU KELI of mattress	870	Heat-clearing and toxic substances removing, dampness removing, soothing liver-QI spleen reinforcing
			Compound Japanese polygala granule	909	Relieving sore-throat by clearing away heat, removing obstruction for relieving pain, expelling phlegm for arresting cough
Support positive removing food stagnancy capsule	945	Spleen invigorating benefit. kidney, change tired removing toxic substances
			BIYANLING PIAN	1208	Removing toxic substances and promoting subsidence of swelling, supplementing QI and nourishing YIN
The clear sheet of skin ulcer	1227	Heat-clearing and toxic substances removing, reducing heat in the blood and treating stranguria

Subarachnoid hemorrhage (SAH) is one of modal emergency case of department of neurology, it is bottom brain caused by Different types of etiopathogenises or brain and the spinal cord vascular surface acute hemorrhagic cerebrovascular diseases of breaking, blood flows directly into subarachnoid space, also known as constitutional or spontaneous subarachnoid hemorrhage.After angiorrhexis blood flows into cranial arachnoid cavity of resorption, cranial cavity content increases, and pressure increases, and can cause a series of complication, as hemorrhage, cerebral vasospasm, cerebral edema again, some patients can have epilepsy, upper digestive tract acute gastric mucosa lesious, pulmonary edema etc.Hemorrhage, cerebral vasospasm, cerebral edema are complication serious after SAH again, are also the main causes that patient SAH is lethal, disable.Therefore remedy measures should should be taked early before these complication occur.The clinical a series for the treatment of means this disease having been formed to standardization diagnosis and treatment at present.But the prognosis of this kind of disease is still undesirable, dead residual rate is up to 45%.A nearest research display, the Patients with Subarachnoid Hemorrhage case fatality rate that emergency treatment is admitted to hospital is 33%.Another studies display, all Patients with Subarachnoid Hemorrhage 30 days case fatality rate 45%, mainly death in the 1st day after morbidity.

The clinical Therapeutic Method of current subarachnoid hemorrhage comprises the following aspects:

1. general treatment: answer hospitalization and monitoring; strict bed rest 4 ~ 6 weeks; head is slightly raised; keep quiet, the comfortable and half-light in ward; avoid that patient is excited, firmly defecation or acutely cough; give calmness; analgesic drug product is as bucinnazine, stable, phenobarbital etc.; available laxative and just softening agent keep free movement of the bowels; blood pressure lowering, keeps blood pressure stabilization level before normal or onset, reduction of patient headache and nervous, exciting emotion; after morbidity, a few hours planted agent carries out cardiac monitoring, monitoring vital sign.The patient of long lasting coma, indwelling catheter, notes nutritional support, prevents complication.

2. the treatment of cranium pressure is fallen: subarachnoid hemorrhage can cause cerebral edema and intracranial pressure to raise, there is cerebral hernia in severe patient, actively should carry out dehydration and fall the treatment of cranium pressure, alone or the conbined usage according to the state of an illness, the medicine dehydration poor effect such as available 20% mannitol, furosemide (furosemide), 20% human albumin and have cerebral hernia may time, feasible subtemporal decompression and ventricular drainage, to save patient vitals.

3. prevention is hemorrhage again: suppress plasminogen to be formed with antifibrinolytics, postpone clot dissolution, prevent hemorrhage generation again.Common drug is 6-aminocaprolc acid, Aminomethylbenzoic Acid, tranamic acid, also available reptilase, etamsylate, carbazochrome salicylate, tranamic acid, thromboplastinum and vitamin K1 etc.Clinical value is had to the Patients with Subarachnoid Hemorrhage going out blood coagulation disorders.

4. prevent and treat chronic cerebral vasospasm: delayed cerebral vasospasm is the main vital of aneurismal subarachnoid hemorrhage and one of the reason that disables, and mechanism is not clear, may be relevant with inflammatory reaction around brain vessel after subarachnoid hemorrhage.Routine should give nimodipine, to reduce the danger of vasospasm and cerebral infarction, should use as early as possible.Oral, or nasal feeding, every day 6 times, took once every 4 hours, each 60mg, as blood pressure falls be not too low, sustainablely use about 21 days.Its side effect has: flushing, headache and feel sick.

5. cerebrospinal fluid displacement therapy: cerebrospinal fluid is put in lumbar puncture, each slowly releasing 10 ~ 20mL, and slowly inject artificial cerebrospinal fluid, 2 times weekly, can intracranial pressure be reduced, alleviate headache, release blood and catabolite, reduce chronic cerebral vasospasm, normal pressure hydrocephalus incidence rate, should note bringing out cerebral hernia, intracranial infection and again bleeding risk, strictly grasp indication.

At present, the report that Chinese medicine is used for subarachnoid hemorrhage clinical treatment is little, comprising conventional western medicine treatment basis adds with red-rooted-salvia-root chuanxiong-rhizome azine injecta, the rheological characteristic of blood samples of patients can not only be improved, reduce the generation of sludged blood, and then improve the circulation etc. of cerebrospinal fluid, the incidence rate etc. of patient lungs's infection or other complication can not only be reduced, but also the rehabilitation of patient can be promoted; In addition, papaverine is used for delayed Cerebral Vasospasm After Subarachnoid Hemorrhage also has research report.

Summary of the invention

The object of this invention is to provide the application of a kind of Herba Hedyotidis Diffusae.

The object of the present invention is achieved like this: the application of this Herba Hedyotidis Diffusae, is characterized in that: Herba Hedyotidis Diffusae is as the application of preparation treatment subarachnoid hemorrhage medicine.

The concrete grammar of described application is select the injection of Herba Hedyotidis Diffusae or freeze dried powder with intravenous drip or intramuscular injection form administration; Minimum amount is adult patient according to BAIHUASHESHECAO ZHUSHEYE according to 2 ~ 4ml/ time, every day 2 times, Herba Hedyotidis Diffusae freeze dried powder 0.5mg ~ 1mg/ time, every day 2 times.

Described subarachnoid hemorrhage comprises the subarachnoid hemorrhage that congenital intracranial aneurysm and Sudden death cause, and also comprises abnormal vascular net disease at the bottom of hypertension, cerebral arteriosclerosis, intracranial tumor, hematopathy, brain (moya-moya is sick), subarachnoid hemorrhage that arteritis, encephalitis, anticoagulant therapy complication and meningitis bring out.

Application advantage of the present invention is:

(1) significantly alleviate the degree of cerebral edema that subarachnoid hemorrhage causes;

(2) promote the absorption of subarachnoid space remained blood;

(3) reduce the destructiveness of blood brain barrier;

(4) alleviate basilar artary vasospasm degree;

(5) improve Neuroscore etc.

By improving above-mentioned several clinical indices and then shielding to cerebral tissue, subarachnoid hemorrhage is had significant therapeutic effect.

The present invention is that the treatment of subarachnoid hemorrhage provides a new way, is described in further detail, but and does not mean that the present invention is only limitted to this below in conjunction with several specific embodiment to the present invention.

Accompanying drawing explanation

Fig. 1 is sham group (sham operated rats), SAH group, OD (2.5) treatment group (BAIHUASHESHECAO ZHUSHEYE 2.5ml/kg administration group) and OD (5) treatment group (BAIHUASHESHECAO ZHUSHEYE 5ml/kg administration group) four groups of degree of cerebral edema compare (mean+SD);

Fig. 2 is brain superficial hemorrhages amount subregion scoring exemplary plot;

Fig. 3 is sham group, SAH group, OD (2.5) treatment group and OD (5) treatment group four groups of spinal subarachnoid space in rats remain blood volume and compare and mark;

Fig. 4 is sham group, SAH group, OD (2.5) treatment group and OD (5) treatment group four groups of Neuroscore (mean+SD);

Fig. 5 sham group, SAH group, OD (2.5) treatment group and OD (5) treatment group respectively organize Blood-Brain Barrier integrity and AZO-blue (EB) assay;

Fig. 6 is sham group, SAH group, OD (2.5) treatment group and OD (5) treatment group respectively organize basilar artary vasospasm scale evaluation.

Detailed description of the invention

The experimental technique used in following embodiment if no special instructions, is conventional method.

Material used in following embodiment, reagent etc., if no special instructions, all can obtain from commercial channels.

The making of embodiment 1. Subarachnoid Hemorrhage in Rats model

We adopt internal carotid artery puncture method to set up rat sah model with reference to documents such as Bederson, and (animal model of subarachnoid hemorrhage adopted in the present embodiment is different from subarachnoid space note blood animal model, this kind of model is closer to clinical patients incidence), getting adult, healthy, body weight is the Sprague-Dawley(SD of 250-300g) rat, fixing with lying on the back after 10% chloral hydrate (3.5ml/kg) intraperitoneal injection of anesthesia.Fixing head and extremity, throat portion preserved skin, sterilization, get cervical region median incision, blunt separation exposes right carotid (common carotid artery, CCA), the ramus anastomoticus between ECA and ICA is cut off in external carotid artery (external carotidartery, ECA) and internal carotid artery (internal carotid artery, ICA) ligation, ECA ligation is cut off stretching, makes itself and ICA in line.Get 3-0 single stranded nylon line (diameter 0.261mm) by head end sharpening, mark in line end 20mm and 22mm place, nylon wire is inserted the intracranial segment of internal carotid artery from external carotid artery, insertion depth is about 20mm, and the 2mm that readvances when feeling there is resistance punctures blood vessel, causes subarachnoid hemorrhage, about 15 seconds rapid afterwards extracts nylon wire, with silk thread ligation external carotid artery stump, recover blood flow, sew up cervical incision.Body temperature 37 DEG C is maintained in art.Sham operated rats is not except puncturing except blood vessel wall, and all the other operations are all consistent with SAH group.Give electric blanket before anesthesia is not clear-headed warming, the single cage of postoperative rat is raised, and notes warming.BAIHUASHESHECAO ZHUSHEYE treatment group is 0.5h, 24h, 47h tail vein injection respectively after SAH, and inject 3 times altogether, injected dose is respectively 2.5ml/kg and 5ml/kg.All the other each group gives normal saline.

Embodiment 2. degree of cerebral edema detects

SD rat is divided into four groups at random, often organize 18, be respectively sham group, SAH group, OD (2.5) treatment group and OD (5) treatment group, according to model preparation method in embodiment 1 and dosage regimen treatment, each group of rat 48h 10 % chloral hydrate anesthesia after SAH, open cranium and get full brain, cut full brain put into rapidly weigh up weight in advance tinfoil paper on weigh, this weight deducts tinfoil paper weight and is weight in wet base W1, put into subsequently after baking box dries 72h under 110 DEG C of conditions and again weigh, this weight deducts tinfoil paper weight and is dry weight W2, cerebral edema index and available following formula are tried to achieve.Cerebral edema index=[(W1-W2)/W1] × 100%.Experimental result such as Fig. 1 shows, and SAH group is compared with sham group, and brain water content exists significant difference, (* * * P<0.01); OD (2.5) group and OD (5) group compare with SAH group respectively, and brain water content all exists significant difference (###P<0.01).Illustrate that BAIHUASHESHECAO ZHUSHEYE significantly can alleviate the degree of subarachnoid hemorrhage associated with hydrocephalus.

After embodiment 3. subarachnoid hemorrhage, each group subarachnoid space remains blood volume measuring

SD rat is divided into four groups at random, often organize 18, be respectively sham group, SAH group, OD (2.5) treatment group and OD (5) treatment group, according to model preparation method in embodiment 1 and dosage regimen treatment, each group of rat 48 h, 10 % chloral hydrate anesthesia after SAH, open cranium and get full brain.Take pictures with high resolution camera, to brain surface, each subregion amounts of bleeding such as Willis ring and basilar artery carry out observing (marking with reference to Fig. 2 example).Basement geology is divided into six parts (as Fig. 2 A), and each several part to divide from 0-3 according to amount of bleeding marks---and 0 point: cavity of resorption is not hemorrhage; 1 point: cavity of resorption has a small amount of blood; 2 points: the blood having moderate on the blood vessel that can distinguish; 3 points: on whole blood vessel, be covered with a large amount of blood (as Fig. 2 B and C).

Aortal grading system in Basement geology: the anterior cerebral artery (ACA) that basilar artery (BA) and Willis ring are formed, internal carotid artery (ICA), nearly rear end cerebral arteries (PCA) from ICA to posterior communicating artery and posterior communicating artery (PcomA) are marked.Middle cerebral artery (MCA), the non-tip of PCA and superior cerebellar artery (SCA) be not in the scope of scoring.Only mark to ensure repeatability and concordance to the blood vessel on Basement geology.

6 part overall scores of blood vessel assign to 18 points from 0.Final score according to animal is divided three classes: 0-7 divides: slight SAH; 8-12 divides: medium SAH; 13-18 divides: serious SAH.Experiment adopts double-blind method.Sham operated rats animal has no hemorrhage, must be divided into 0 point.

As shown in Figure 3, Fig. 3 A is that after modeling, 48h respectively organizes subarachnoid space and remains blood volume audio-visual picture to experimental result; Fig. 3 B is the appraisal result of each group of subarachnoid space blood volume: SAH group is compared with sham group, and subarachnoid space blood volume exists significant difference (* * * P<0.01); OD (2.5) group is compared with SAH group, and subarachnoid space blood volume significantly reduces, and there is significant difference (#P<0.01); OD (5) group compares with SAH group, and subarachnoid space blood volume significantly reduces, and also there is significant difference (###P<0.01).Illustrate that BAIHUASHESHECAO ZHUSHEYE can promote the absorption of remained blood after subarachnoid hemorrhage, thus reduce the correlated response bad to the stimulation of cerebral tissue and inflammation etc. such as hemoglobin.

Example 4. rat behavior-Neuroscore

SD rat is divided into four groups at random, often organizes 18, be respectively sham group, SAH group, OD (2.5) treatment group and OD (5) treatment group, according to model preparation method in embodiment 1 and dosage regimen treatment.In postoperative 24h, behavioristics's Neuroscore is carried out to each treated animal with reference to Sugawara standard.Minimum point: 3 points, best result: 18 points.Score value is lower shows that the neurological deficit of animal is more serious.

(1) voluntary activity: rat is placed in cage and observes 5 minutes, marks according to the contact of cage wall.3 points: be free to motion, cage at least 3 side can be contacted; 2 points: cage sidewall can be touched, but less than 3 sides; 1 point: only can shift position; 0 point: can not move.

(2) quadruped locomotion is symmetrical: rat is carried the movement symmetry that tail is placed in its extremity of aerial observation.3 points: extremity are symmetrical, with no significant difference before arachnoid hemorrhage; 2 points: limb adynamia or bradykinesia; 1 point: limbs are extremely unable, only have light activity; 0 point: limbs can not move.

(3) forward foot in a step is stretched: rat is carried the edge of tail to desk, allow its forward limb move ahead, and observation is when the stretching, extension situation close to forelimb during desktop.3 points: two forelimb extensions is with before subarachnoid hemorrhage; 2 points: foreleg stretches calibration constant; 1 point: foreleg only has slight stretching, extension; 0 point: foreleg attonity.

(4) climb: be placed in by rat on vertical 10cm × 100cm wire netting, time normal, rat extremity swash, and carry tail and make rat leave cage, observation rat limb force.3 points: creep easily, keep a firm hand on wire netting strong; 2 points: climbing difficulty; 1 point: can not climb.

(5) touching of bilateral trunk is reacted: with blunt nosed wooden stick stimulation in rats side health, observe it to the reaction stimulated.3 points: the rapid rotary head of rat, Bilateral Symmetry; 2 points: only have slight reaction; 1 point: reactionless to the touching of trunk.

(6) antenna reaction: blunt nosed wooden stick stimulates side beard, and wooden stick touches beard from behind and avoids rat to see wooden stick.3 points: Bilateral Symmetry reacts; 2 points: minor response; 1 point: reactionless.

As shown in Figure 4, SAH group is compared with sham, and behavioristics's Neuroscore exists significant difference (* * * P<0.01) for result; OD (2.5) group and OD (5) group compare with SAH group respectively, and neurological deficit score is significantly increased, and there is significant difference (###P<0.01).Illustrate that BAIHUASHESHECAO ZHUSHEYE can significantly improve the behavioral competence of animal after subarachnoid hemorrhage, reduce the damage of function of nervous system.

Example 5. blood-brain barrier permeability measures

SD rat is divided into four groups at random, often organizes 18, be respectively sham group, SAH group, OD (2.5) treatment group and OD (5) treatment group, according to model preparation method in embodiment 1 and dosage regimen treatment.Then according to the following step, blood-brain barrier permeability is detected:

(1) Criterion curve: preparing 0.1 mg/ml EB solution is initial concentration liquid, carry out doubling dilution, form the EB normal concentration of gradient solution 0.1,0.05,0.025,0.0125,0.0063, application UV detector 620nm carries out colorimetric, formamide solution does blank, carries out regression analysis and tries to achieve standard curve.

(2) after rat anesthesia through vena femoralis injection 2% EB (5 ml/kg), put to death after 1h, for removing dyestuff in blood, ventricles normal saline is till right ventricle flows out transparency liquid left, brain is got after broken end, be divided into left brain, right brain and cerebellum three parts, immerse in formamide solution by 10ml/g after weighing, extracting 24h in 60 DEG C of constant water bath box, formamide solution presents the different blueness of the depth, cerebral tissue presents water white transparency shape, then applies UV detector and carries out colorimetric, wavelength setting 620nm.EB content is calculated according to standard curve.

As shown in Figure 5, in L.H (left half brain), R.H (right half brain) and C (cerebellum) three Different brain region, SAH group is compared with sham group, and in cerebral tissue, EB content is significantly higher than sham group (* P<0.01); OD (2.5) group and OD (5) group compare with SAH group respectively, and in cerebral tissue, EB content is significantly lower than SAH group (#P<0.01).These experimental datas show, and BAIHUASHESHECAO ZHUSHEYE significantly can reduce the destructiveness of blood brain barrier, improve the integrity of blood brain barrier, play a protective role to cerebral tissue.

The angiospastic detection of example 6. rat brain

SD rat is divided into four groups at random, often organizes 18, be respectively sham group, SAH group, OD (2.5) treatment group and OD (5) treatment group, according to model preparation method in embodiment 1 and dosage regimen treatment.Test according to following method:

One, draw materials: experimental rat opens breast through left side, cut off pericardium and expose heart, on diaphram, thoracic cavity inner clip closes thoracic aorta and postcava, puncture in apex of the heart place with 27G remaining needle, and remaining needle is put ascending aorta, then right auricle is cut off, first with the normal saline flushing containing heparin (20 U/ml), measure about 150-200ml, get rid of vessel inner blood, then and with 4% paraformaldehyde heart perfusion, speed first quick and back slow, infusion time is about 10min ~ 15min, measure about 250-300ml, can find in this process, rat neck is hardening gradually, the two upper limb of rat or tic of the limbs.After perfusion terminates, open cranium and get brain, observe hematocele situation around brain Basement geology and Willis arterial ring, then tissue specimen is soaked in 4% paraformaldehyde and spends the night.

Two, HE dyeing: the gross morphology structure of main display basilar artery.

Staining procedure is as follows:

(1) paraffin section enters each 10 min of dimethylbenzene I, II dewaxing;

(2) each 3 min of dehydrated alcohol I, II, each 5s of graded ethanol 95%, 90%, 85%, 80%, 70%, distillation washing;

(3) haematoxylin dyeing 4 min;

(4) 1% hydrochloride alcohol color separation 2s, basis of microscopic observation grasps color separation degree;

(5) 20min is washed from the beginning, oil blackeite;

(5) eosin stains liquid is immersed (0.5%) 1 minute;

(8) each 1min of graded ethanol 90%, 95%, each 5min of dehydrated alcohol I, II;

(9) the transparent each 5min of dimethylbenzene I, II;

(10) neutral gum mounting.

Three, measure: get every Rat Basilar HE stained, take pictures under Nikon optical microscope, reference literature method [3] is by measuring basilar artery Lumen Area determination vasospasm degree.Adopt Image Pro Plus image analysis system computer tube cavity area and gross area ratio, finally apply SPSS 17.0 and carry out statistical analysis.

Experimental result as shown in Figure 6, Fig. 6 A: each group basilar artery metamorphosis (HE, 200); Fig. 6 B: each group vasospasm degree statistical: 2 days and 7 days SAH groups compare with sham group, vasospasm degree all increases, and there is significant difference (* P<0.01); OD (2.5) group and OD (5) group compare with SAH group respectively, and vasospasm degree is all remarkable in SAH group (###P<0.01).Experimental result illustrates, BAIHUASHESHECAO ZHUSHEYE effectively can prevent the angiospastic generation of basilar artary.

In sum, the present invention is confirmed by a large amount of animal experiment in vivo, and Herba Hedyotidis Diffusae has definite therapeutic effect in the treatment of the brain injury of subarachnoid hemorrhage.

Claims (3)

1. an application for Herba Hedyotidis Diffusae, is characterized in that: Herba Hedyotidis Diffusae is as the application of sole active composition at preparation treatment subarachnoid hemorrhage medicine.

2. the application of Herba Hedyotidis Diffusae according to claim 1, is characterized in that: the concrete grammar of described application is select the injection of Herba Hedyotidis Diffusae or freeze dried powder with intravenous drip or intramuscular injection form administration; Minimum amount is adult patient according to BAIHUASHESHECAO ZHUSHEYE according to 2 ~ 4ml/ time, every day 2 times, Herba Hedyotidis Diffusae freeze dried powder 0.5mg ~ 1mg/ time, every day 2 times.

3. the application of the Herba Hedyotidis Diffusae described in claim 1 or 2, it is characterized in that: described subarachnoid hemorrhage is the subarachnoid hemorrhage that congenital intracranial aneurysm and Sudden death cause, the subarachnoid hemorrhage that at the bottom of hypertension, cerebral arteriosclerosis, intracranial tumor, hematopathy, brain, abnormal vascular net disease, arteritis, encephalitis, anticoagulant therapy complication and meningitis bring out.