CN102743734A - Application of Tianlou Guizhi decoction in treatment of post-stroke spasm - Google Patents
Application of Tianlou Guizhi decoction in treatment of post-stroke spasm Download PDFInfo
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Abstract
The invention discloses an application of Tianlou Guizhi decoction in treatment of post-stroke spasm. The decoction comprises the following materials: 15-45 parts of Radix Trichosanthis, 4.5-13.5 parts of Ramulus Cinnamomi, 4.5-13.5 parts of Radix Paeoniae Alba, 3-9 parts of Radix Glycyrrhizae, 4.5-13.5 parts of Rhizoma Zingiberis Recens and6-18 parts of Fructus Jujubae. The decoction has definite curative effect, and facilitates rehabilitation training.
Description
Technical field
The invention provides the new purposes of Fructus Trichosanthis guizhi decoction, belong to drug world.
Background technology
" Fructus Trichosanthis guizhi decoction " comes from Eastern Han Dynasty's Zhang Zhongjing in the last years of a dynasty or reign " Medical Treasures of the Golden Chamber ", and " convulsion wet excessive pathogenic heat in febrile disease abnormal pulse card second " piece of writing is said: " TAI YANG syndrome, its card is equipped with, rigidity of the body is several right, arteries and veins is instead late heavy, this is a convulsion, Fructus Trichosanthis guizhi decoction master it." square medicine composition: 2 liang of Radix Trichosanthis, 3 liang of Ramulus Cinnamomi, 3 liang of the Radix Paeoniae Albas, 2 liang in Radix Glycyrrhizae, 3 liang in Rhizoma Zingiberis Recens (cutting), 12 pieces in Fructus Jujubae (thumb).Instructions about how to take medicine and taboo: last 6 flavors, with water 9L, boil and get 3L, divide temperature 3 clothes, get slight perspiration, no sweating, food is tired, sobs hot medicated porridge.Former side mainly treats the rigidity with sweating of sun perspiration and aversion to wind, and pathogenesis is evil resistance muscle arteries and veins, dysfunction of both nutrient QI and defernsive QI, and cardinal symptom is main with the strong discomfort of health.Effect: expelling pathogenic factors from muscles is eliminating evil, the muscle arteries and veins of releiving.Cure mainly: sun rigidity with sweating body is demonstrate,proved by force.Disease is seen stiffness of the nape and back, limbs contracture, heating, aversion to wind and cold, headache sweating, white and thin fur, deep-thready pulse and slow or double string.Clinical application: originally can be widely used in infectious disease, allergic disease, diseases of mental and nervous system, stiff neck, hyperosteogeny of cervical vertebra, lumbar muscle strain, xerosis cutis syndrome, chronic nephritis, nephrotic syndrome, nervous tinnitus etc. and belong to above-mentioned card machine person.There is report to add Pachyrhizua angulatus, Radix Rehmanniae treatment mental sickness with we; With the we treatment children's disease (deficiency of vital energy adds Radix Codonopsis, the insufficiency of the spleen Rhizoma Atractylodis Macrocephalae that adds, blood deficiency adds Radix Angelicae Sinensis, the deficiency of YIN adds Herba Dendrobii) of twitching; Close kudzuvine root for treating exterior syndrome etc. and all obtain good result.Number of patent application: 200910092548.2, denomination of invention: a kind of Chinese medicine composition of treating child's spastic cerebral palsy, the present invention relates to a kind of Chinese medicine composition that is used to treat child's spastic cerebral palsy, belong to the Chinese medicine technical field of pharmaceuticals.Chinese medicine composition of the present invention; By 3～18 parts of Radix Trichosanthis, 6～30 parts of Radix Puerariaes, 6～24 parts of Ramulus Cinnamomi, 6～24 parts of the Radix Paeoniae Albas, 3～18 parts in Radix Glycyrrhizae, 6～24 parts in Rhizoma Zingiberis Recens, 6～60 parts in Fructus Jujubae; Umber proportioning according to required weight; Adopt and smooth QI and blood, harmonizing yingfen and weifen, the nourishing YIN that promotes the production of body fluid, gentle smooth muscle feeling pulse method, can be made into decoction, tablet, pill, powder, mixture, drop, capsule, electuary etc., be used to treat child's spastic cerebral palsy.
Cerebral palsy is the substantive damage of brain cell, atrophy, causes cooperation imbalance between each nervous system of maincenter, a series of no purposes, not normal action occur, the action that brain can not command limbs to coordinate.Diseased region is many in the marginal zone of brain, and the marginal zone cell dysfunction makes the nervus centralis conductive obstruction, dyskinesia occurs, is not that quadriplegia is inactive.Cerebral palsy is one group of heterogeneous non-carrying out property syndrome, it is characterized by motion and abnormal posture.These show that the seriousness aspect is different, are because the caused by abnormal of the growth midbrain that a variety of causes causes.Although itself does not make progress disease, its neuro pathology's pathological changes and clinical manifestation thereof change along with the maturation of brain.Research in recent years shows, period of fetus and neonatal cerebrovascular disease, infection, brain development are bad, dysbolismus, autoimmune and dysfunction of blood coagulation etc. all can cause baby's cerebral lesion.The morbidity of cerebral palsy is a kind of result of multifactor effect, and big multifactor closely related with genetic predisposition.The cerebral palsy risk factor is followed successively by: hypoxic ischemic encephalopathy of newborn, previously bad motherhood history, amniotic fluid is unusual, fetal head attracts or obstetric forceps practise midwifery, multiple pregnancy, in utero poverty-stricken, premature rupture of fetal membrane, asphyxia of newborn, pregnant time greater than 1,10 independent hazard factors such as hyperbilirubinemia of newborn.But when producing and puerperal risk factor be likely the outcome variable that antenatal factor causes, rather than the direct cause of disease of cerebral palsy.
The cerebral palsy of children especially key of spastic cerebral palsy rehabilitation is discovery early, intervention early, early treatment, rehabilitation early.The brain growth promoter in infant period is fast, and compensatory and plasticity are strong, is the best period of study.Give zest treatment and functional training from the external world in this period, can make infant in the rehabilitation process, constantly correct unusual study, set up normal pattern and function, reach optimum efficiency.Observation shows that most of spastic cerebral palsy levies positive sign with kernig.When meningeal irritation sign is meninges and the infringement of nerve root irriate property, the sign that produces because of relevant muscle group reflexive spasm.The visible neuron of known CP children brain pathological change is downright bad.Mainly in the white matter of brain and XIAONAO, severe patient can cause the cerebral cortex diffuse necrosis to pathological changes, and gyrus can be paralysed trace property gyrus, and thalamus and brain stem neuron are also visible downright bad.These pathological changes possibly relate to meninges, cause meningeal irritation sign.As the abdominal muscle spasm of peritonitis or tetanic the same, meningeal irritation sign is a kind of reflex muscular defence phenomenon.Then inspire intensive pain when therefore muscle receives tractive.Body is made defensive attitude for avoiding this pain, like flexing limbs etc.The secular defensive attitude of this kind just becomes odd-shaped another major reason of limbs flexing spasm.To spasm due to the cerebral palsy, one type of medicine utilizes this type of medicine to promote metabolism, the blood circulation of brain for improving the medicine of brain function at present, alleviates cerebral anoxia, replenishes the required nutrient substance of brain development, the resistance of enhancing body.The growth of neurocyte and the growth of aixs cylinder all there is good action; Can select the medicine that promotes brain injury reparation and growth for use, like vitamin B group, peptide class, protein; The brain cell activator is used nerve growth factor, injection GM-1, Cerebrolysin, mouse nerve growth factor, Energy mixture etc. always.Later do not advocate to select for use a large amount of medicines that improve brain function in 1 year old, emphasis is main with rehabilitation training.Another kind of for improve dyskinetic medicine commonly used the muscular tension medicine of reduction such as baclofen, dantrolene, dantrolene sodium etc. are arranged.
Apoplexy also is apoplexy, is the hemorrhage or cerebral infarction of rupture of blood vessel in brain, and the hemiplegia of one side disorder of limb ' s activity of cranial nerve conductive obstruction occurs, in case absorption of hemorrhage or vascular patency, hemiplegia will take a turn for the better.The apoplexy modern medicine is divided into Ischemic Stroke, hemorrhagic apoplexy; One of three big diseases that threaten human health have been become at present; According to statistics, there is deformity in various degree in about 70%-80% in the survivor, and particularly the post-stroke limbs disturbance has become serious social concern day by day; Wherein the appearance of spasm has hindered the recovery of patient's limb function significantly, and its characteristics are the muscular hypertonia of paralysis side limbs, tendon hyperreflexia, clonic spasm and myotonia occur.Although spasm is the hemiplegia common complication, be not that all spasm all are harmful to and need special treatment.The spasm of appropriateness can be kept muscle volume and mineralization of skeleton, increases the stability of hip and trunk, helps patient safety and moves, and can reduce the incidence rate of DVT and pulmonary infarction.But spasm Chang Buneng is stabilized on the useful level, and develops into serious spasticity easily, makes the patient pain occur, influences the voluntary movement of limbs, causes arthrogryposis, hinders the perineal position health, influences standing balance and activity of daily living; During night's rest, uncontrollable spasm often influences patient's ortho sleep.Therefore, the high rate of limbs muscular spasm, the difficulty in the treatment get involved the importance to limb function rehabilitation early after the apoplexy, have made it become the difficult point and the emphasis of rehabilitation after the apoplexy.Effective treatment approach of limbs muscular spasm is one of important topic of rehabilitation medicine worker after the research apoplexy.
Hemiplegia spasticity (Spasticity) is one of topmost dysfunction of apoplexy, and sickness rate is up to 80%, have more present apoplexy after a couple of days to several weeks.6 stages of Brunnstrom apoplexy propose, and increasing of muscular tension is an important stage of central nervous system function recovery process, and it directly influences spastic paralysis patient's prognosis.Hard paralysis phase obstacle of limb movement: post-stroke is because kentrokiness suppresses unbalance of system; Make A-MN and gamma motor neuron mutual restriction, interact unbalancely, cause gamma motor neuron to preponderate, make kentrokiness suppress systemic effect and weaken; Cause the original function of low-level center to discharge; Cause the irritability of motor circuit to strengthen, make the affected limb muscular hypertonia, be spasticity.Clinically, have more existing flexion of upper limb muscle group and extensor of leg crowd muscular hypertonia, form so-called Wernicke-Mann position.Clinical observation finds that body firmly can increase the weight of spasm, and strengthens unusual motor pattern, thereby the moving-mass of apoplexy patient and motor control are worsened, and influences the recovery of motor function.Post-stroke patient muscular hypertonia clinical mainly shows as the muscular hypertonia of upper limb musculus flexor (receipts and elbow, wrist and hand joint flexing in the shoulder joint) and extensor of leg (hip, knee joint are stretched and opened up in the wrong with ankle joint), and often with tendon hyperreflexia, clonic spasm, congener-Antagonistic muscle co-contraction, pathology levy, weak and fatigue etc.Because the appearance of spasm has limited the trouble limb and learnt voluntomotory ability again, even " misuse syndrome " can occur, causes arthrogryposis and pressure ulcer etc., hinder the recovery of patient's neuromuscular function.
At present to the mechanism of the spasticity of post-stroke; It is generally acknowledged; Spasm is that the spinal reflex activity of UM damage back is increased and caused, strengthening with the speed dependence stretch reflex is that the muscle tone of characteristic is unusual, be hyperfunction with stretch reflex be due to the motor control disorder of core.Post-stroke hemiplegic limb spasm mainly is that the spinal center irritability increases, and particularly α-γ loop activeness strengthens and causes.To spastic paralysis after the apoplexy, modern medicine is generally taked the method treatment of medicine, various physical chemistry Therapeutic Method and operative treatment.Drug treatment does not still have specific medicament, at present central spasmolytic and two types of Drug therapys of periphery property spasmolytic used more.
Summary of the invention
Technical scheme of the present invention has provided the new purposes of Fructus Trichosanthis guizhi decoction, particularly, is the purposes in the medicine of preparation treatment post-stroke limb spasm.
The invention provides and contain the purposes of following raw materials by weight proportions in the medicine of preparation treatment post-stroke limb spasm:
Radix Trichosanthis 15-45 part, Ramulus Cinnamomi 4.5-13.5 part, Radix Paeoniae Alba 4.5-13.5 part, Radix Glycyrrhizae 3-9 part, Rhizoma Zingiberis Recens 4.5-13.5 part, Fructus Jujubae 6-18 part.
Wherein, described medicine is the medicine of treating post-stroke hemiplegia spasm and alleviating the obstacle of limb movement that is caused by spasm.
Further preferably, described medicine is the preparation that is prepared from following raw materials by weight proportions:
30 parts of Radix Trichosanthis, 9 parts of Ramulus Cinnamomi, 9 parts of the Radix Paeoniae Albas, 6 parts in Radix Glycyrrhizae, 9 parts in Rhizoma Zingiberis Recens, 12 parts in Fructus Jujubae.
Wherein, described medicine is the protogenic medicinal powder by Radix Trichosanthis, Ramulus Cinnamomi, the Radix Paeoniae Alba, Radix Glycyrrhizae, Rhizoma Zingiberis Recens, Fructus Jujubae, or water or extractive with organic solvent be active component, adds the preparation that acceptable accessories or complementary composition are prepared from.
Wherein, described preparation is tablet, granule, oral liquid, capsule, pill.
Wherein, the method for preparing of described medicine comprises the steps:
A, take by weighing each materials of weight proportions medicine;
B, the Radix Paeoniae Alba are ground into fine powder, sieve;
C, get Ramulus Cinnamomi, Rhizoma Zingiberis Recens water vapour distillation volatile oil, subsequent use;
D, Radix Trichosanthis, Radix Glycyrrhizae, Fructus Jujubae, Ramulus Cinnamomi, the decocte with water of Rhizoma Zingiberis Recens medicinal residues after the c step is extracted are filtered, and filtrating is condensed into clear paste; Add the Radix Paeoniae Alba fine powder of b step preparation, the volatile oil of c step in the clear paste, mixing adds acceptable accessories or complementary composition, is prepared into preparation pharmaceutically commonly used.
Radices trichosanthis in the medicine material medicine of the present invention, i.e. Radix Trichosanthis, amount heavily be a monarch drug, sweet, the little hardship of its nature and flavor is slightly cold, and gets its clearing away heat and promoting production of body fluid, the soften effect of muscle of yin nourishing.The Radix Paeoniae Alba, nature and flavor are sour, bitter, cool, and nourishing blood to suppress the hyperactive liver is arranged, slow middle pain relieving, yin fluid astringing is received the merit of antiperspirant, and consumption residence two is a ministerial drug in the raw material prescription.Ramulus Cinnamomi, hot, sweet, warm, the diaphoresis expelling pathogenic factors from muscles is arranged, warming the meridian and promoting blood circulation, supporing yang activating QI, the merit of dispersing cold for relieving pain.The Radix Paeoniae Alba, Ramulus Cinnamomi and radices trichosanthis share, and have pind down the cold and cool property of radices trichosanthis, help the effect of radices trichosanthis dredging the meridian again.The Radix Paeoniae Alba, Ramulus Cinnamomi two medicines share in the side, and the merit of sour and sweet drugs can transforme into YIN is arranged, and YIN-fluid of human is recovered, and the muscle arteries and veins must be supported, and gentle muscular atonia is anxious, and pain is not given birth to.Rhizoma Zingiberis Recens, Fructus Jujubae, Radix Glycyrrhizae have the effect of warming middle-JIAO emergency.YIN fluid being insufficient causes limb spasm after being used to treat patient's apoplexy, spasm of limbs, and disease is seen: the trouble limb is stiff, contracture pain, xerostomia happiness drink, it is dried partially to defecate, red tongue or light red tongue, yellow and thin fur (or few tongue), thready pulse (number) or string.
Medicine of the present invention is used to treat the post-stroke limb spasm, and drug effect is clear and definite, and can play facilitation to rehabilitation training.
Description of drawings
The scoring of Fig. 1 neuroethology.
Fig. 2 on-Line review testing evaluation.
Fig. 3 TTC colored graph.
Fig. 4 h reflex figure.
Fig. 5 glutamic.
The specific embodiment
The preparation of embodiment 1 medicine of the present invention
1, raw material prescription: Radix Trichosanthis 30g, Ramulus Cinnamomi 9g, Radix Paeoniae Alba 9g, Radix Glycyrrhizae 6g, Rhizoma Zingiberis Recens 9g, Fructus Jujubae 6 pieces (thumbs) are (12g)
2, method for making
Above Six-element, the Radix Paeoniae Alba is ground into fine powder, sieves; Ramulus Cinnamomi, Rhizoma Zingiberis Recens extract volatile oil; Radix Trichosanthis, Radix Glycyrrhizae, Fructus Jujubae and extract volatile oil after Ramulus Cinnamomi, Rhizoma Zingiberis Recens medicinal residues, add 10 times of water gagings, decocts 2 times, each 1.5 hours, filtration; Merging filtrate, filtrating is concentrated into the clear paste that relative density is 1.30 (30 ℃), adds Radix Paeoniae Alba fine powder, Ramulus Cinnamomi, the volatile oil of Rhizoma Zingiberis Recens through extracting; An amount of dextrin, mixing is processed granule; 50-60 ℃ of drying, the system granule promptly gets.
The preparation of embodiment 2 medicines of the present invention
Get 6 pieces of crude drug Radix Trichosanthis 15g, Ramulus Cinnamomi 4.5g, Radix Paeoniae Alba 4.5g, Radix Glycyrrhizae 3g, Rhizoma Zingiberis Recens 4.5g, Fructus Jujubae, directly beat powder, encapsulated, be prepared into capsule.
The preparation of embodiment 3 medicines of the present invention
Get 18 pieces of crude drug Radix Trichosanthis 45g, Ramulus Cinnamomi 13.5g, Radix Paeoniae Alba 13.5g, Radix Glycyrrhizae 9g, Rhizoma Zingiberis Recens 13.5g, Fructus Jujubae, directly decocte with water concentrates, concentrated solution.
Below prove beneficial effect of the present invention through concrete clinical trial and pharmacodynamics test.
The research of Test Example 1 Drug therapy post-stroke limb spasm of the present invention
Physical data: the patient of limb spasm was as object of study after this research was chosen the apoplexy of being in hospital in rehabilitation lesion, the attached the People's Hospital of Fujian university of TCM year May in March, 2012 to 2012 and comprised cerebral hemorrhage, cerebral infarction.The patient who meets screening criteria and final completion observation amounts to 13 examples, all goes into to organize patient and is divided into treatment group and matched group according to the table of random number method, is respectively 6 example and 7 examples, and concrete condition is following.
The comparison of patients with cerebral apoplexy physical data
Relevant criterion: the apoplexy diagnostic criteria is with reference to " the apoplexy diagnostic criteria " of in January, 1996 State Administration of Traditional Chinese Medicine's encephalopathy emergency case cooperative groups announcement; The apoplexy diagnostic criteria is with reference to nineteen ninety-five Chinese Medical Association " the 4th the diagnosis and treatment of cerebrovascular diseases main points that national cerebrovascular academic conference is worked out ".Include standard in: a. meets above-mentioned Chinese and western medicine diagnostic criteria.B. the state of an illness is basicly stable, with the Ashworth scale evaluation paralyzed limbs muscular tension 1-3 level of improvement.C. fell ill 3 months in.D. diagnosis of cerebral apoplexy first.The patient of the muscular spasm due to the non-cerebrovascular disease of exclusion standard: a..B. coma or vital sign instability person.C. fear treatment or disoperative patient.D. merge the serious heart, lung, liver, kidney disease and psychotic.
Therapeutic Method:
Matched group: the rehabilitation training group is main with adult's training hemiparalysis method of bobath mainly.The therapist trains one to one, and 1 time/day, treat 6 days (not treating on every Sundays) weekly, guarantee the correct placement of training time of having a rest spasmolytic position.4 weeks of the course of treatment.
The treatment group: Fructus Trichosanthis guizhi decoction+rehabilitation training group with the basis of the identical rehabilitation of matched group on accept the treatment of Fructus Trichosanthis guizhi decoction.Concrete grammar is following:
Side's medicine: 6 pieces of radices trichosanthis 30g, Ramulus Cinnamomi 9g, Radix Paeoniae Alba 15g, Radix Glycyrrhizae 6g, Rhizoma Zingiberis Recens 9g, Fructus Jujubae
Medication preparation: the prepared slices of Chinese crude drugs adopt full-automatic boiling machine to boil medicine from Chinese medicine pharmacy.Instructions of taking: decocting l every day agent, fry in shallow oil 2 each 200ml of bag, sub-service sooner or later for 1 dose.4 weeks of the course of treatment.
Observation of curative effect:
A. observation cycle: Drug therapy is uninterrupted, treats 6 days (not treating on every Sundays) weekly rehabilitation training every day 1 time, is for 4 weeks the course of treatment.Rehabilitation evaluation before treatment, treatment respectively evaluates 1 time after 4 weeks.Various evaluations are undertaken by same doctor, and this doctor does not participate in treatment, and do not know the grouping situation.Surface electromyography detects respectively in treatment preceding 1 day, and treatment finishes the back and respectively detected 1 time in the 1st day, detects the doctor and does not know the grouping situation.
B. observation index: a. improvement Ashworth spasm grading scale scoring b. daily life active ability improvement Barthel index scoring c. extremity motor function Fugl-Meyer evaluation and test.
C. date processing: adopt SPSS17.0 medical statistics software.Determination data is represented with mean ± standard deviation x ± s.Select for use complete analysis collection and the data that meet scheme set to analyze respectively to main observation index; Select for use the data that meet scheme set to analyze to less important observation index.Relatively adopt the t check between two groups, paired t-test is relatively adopted in front and back, and enumeration data is used X 2 test, and dependency relation adopts the simple correlation analysis between parameter.
Therapeutic outcome:
Improvement Barthel index rating scale
Simplify the evaluation of Fugl-Meyer motor function
Relatively, two scales are two groups of treatment front and back evaluations before and after the treatment, and < 0.05, difference has significance before and after the treatment, and two groups all effective to be P.
Curative effect relatively between two groups.
With the evaluation of improvement Barthel index rating scale, < 0.05, treatment group curative effect is superior to matched group to P; And to simplify the evaluation of Fugl-Meyer motor function, P＞0.05, treatment group and matched group curative effect indifference.
Medicine of the present invention is used to treat limb spasm after the apoplexy, and it is good to produce effects.The result: on the same group before and after the treatment relatively, two scale scorings are improved (P < 0.05), difference has significance before and after the treatment, two groups are all effective.With after the treatment of control group relatively, the scoring of improvement Barthel index improves obviously, difference has statistical significance (P < 0.05).With comparison after the treatment of control group, extremity motor function Fugl-Meyer scoring improves no significant difference.Conclusion; The Fructus Trichosanthis guizhi decoction is effective to treatment post-stroke limb spasm, and is helpful to the raising of patient's daily life active ability, and can play facilitation to rehabilitation training.
Test Example 2 medicine effects of the present invention are learned test
1 experiment material
1.1 laboratory animal
Healthy cleaning level Wistar rat, male, body weight 250～300g is provided by Fujian university of TCM Experimental Animal Center.Buy the last week in experiment, animal is divided cage, quiet, keep away high light and airy experiment indoor feeding, 22 ± 2 ℃ of constant temperature, naturally round the clock, free drinking water.Water is can't help in the fasting in 12 hours of rat perioperatively.
1.2 main agents, instrument
Chloral hydrate, 4% paraformaldehyde phosphate buffer, TTC dye liquor ((contain 4%TTC1.5m1 in every 5m1 dye liquor; 1MK2HP040.1m1 all the other adding distil waters are to scale), pipettor, electronic balance, medical aseptic operating theater instruments, superclean bench, electrophresis apparatus, fluorescence microscope, laser confocal microscope.
2 experimental techniques
2.1 laboratory animal is divided into groups
Animal is divided into 3 groups at random, dose groups in sham operated rats, model group, the Fructus Trichosanthis guizhi decoction (embodiment 1 preparation).
1. sham operated rats: only separate tremulous pulse, not ligation, plug wire.Give the equal volume normal saline and irritate stomach.
2. model group: make the cerebral infarction rat model, give the equal volume normal saline and irritate stomach.
3. dose groups in the Fructus Trichosanthis guizhi decoction: the treatment of dosage Fructus Trichosanthis guizhi decoction is 7 days in giving after the modeling.
2.2 modelling
Preparation focal cerebral ischemia animal model: stopping up under 22 ℃ of conditions of temperature, with reference to Zea Longa method, row left side MCAO (middle cerebral artery occlusion, MCAO) operation.All rats all select middle cerebral artery district, left side as the infarction side.Animal is weighed, and presses 30mg/kg dosage through lumbar injection 10% chloral hydrate anesthesia.Postanesthetic rat lain on the back to be fixed on the operating-table, after the preserved skin sterilization, cuts skin along the cervical region left side, along sternocleidomastoid inner edge separating muscle and fascia, separates left carotid (CCA), external carotid artery (ECA), and with No. 0 toe-in bundle.Separate internal carotid artery (ICA), be equipped with line at the ICA near-end, far-end is placed bulldog clamp; Expand place's otch in internal carotid artery and external carotid artery bifurcated; Fishing line is inserted internal carotid artery, and the plug wire place of ligation CCA bifurcated slightly removes the bulldog clamp of ICA far-end then; Fishing line taken advantage of a situation slowly send into; Cross the near-end of arteria pterygopalatina, stop plug wire during the about 18～20mm of the degree of depth, cause cerebral ischemia with the blood flow of blocking this side middle cerebral artery until the intracranial anterior cerebral artery.After plug wire finishes, with ICA and fishing line ligation together.Stay about 10mm fishing line behind the disinfection and stitching outside skin, carefully fishing line is outwards extracted after 2 hours, make the fishing line pommel retreat to CCA, realize perfusion again.The modeling post processing: infection, lumbar injection penicillin 20,000 units were injected 3 days continuously, and single cage is raised, and strengthens feeding.Sham operated rats is only cut skin, behind separation of C CA, ECA, the ICA, and not ligation, threading, disinfection and stitching.
2.3 model is judged
1. model evaluation: the evaluation to the nerve injury of MCAO model has Zealonga5 to divide evaluation methodology, and the nervous symptoms that occurred in back 2 hours according to the infraction of model mouse is divided into the 0-4 branch with nervous lesion, and 1-3 divides the success of explanation model:
0 minute: the impassivity functional impairment;
1 minute: receive in the right fore when carrying tail, can not full extension;
2 minutes: turn-take to the right during spontaneous walking;
3 minutes: health was toppled over to the right during walking;
4 minutes: can not spontaneously walk, consciously forfeiture.
2. spasm evaluation: improvement Ashworth grade assessment method, muscular tension reaches the I level and is the model success more than the I level:
0 grade: no muscular hypertonia, activities in rats are freely;
The I level: muscular tension slightly increases, show as when the part passive flexion and extension of getting involved to the end of ROM (Range of motion) the very little resistance of appearance, or occur unexpected block and discharging;
I
+Level: muscular tension slightly increases, and when showing as passive flexion and extension, unexpected blocking occur, and in back 50% scope of ROM, presents extremely slight resistance all the time then;
The II level: muscular tension more obviously increases in the major part of ROM, but the part of getting involved still is easier to be moved;
The III level: muscular tension seriously increases, the passive activity difficulty;
The IV level: the part of getting involved flexing or stretch the position tetanic.
2.4 pharmaceutical intervention method
1. medicine is formed and dosage:
Radices trichosanthis 30g Ramulus Cinnamomi 9g Radix Paeoniae Alba 9g Radix Glycyrrhizae 6g
6 pieces in Rhizoma Zingiberis Recens 9g Fructus Jujubae
2. the administration time and the course of treatment:
According to the dose estimation conversion method on " herbal pharmacology research methodology ", rat is 0.6g/ml corresponding to people's common dose, with this as in dose groups, beginning in the 1st day administration in modeling success back, 1 time/day, continuous irrigation stomach 7 days.
2.5 zoopery detects sample process
Carry out the detection of each item index after each treated animal finishes respectively at treatment in the 7th day, after behavioristics and the end of neuroelectricity physiological detection, disconnected neck is put to death animal, detects requirement by index and draws materials, handles, preserves experiment detection sample.Carry out statistical disposition after obtaining the detection data.
2.5.1 behavioristics is observed
1. neuroethology Zealonga5 divides assessment method.
2. screen test (screen test): screen is a 50cm X40cm guipure, and mesh is lcm X lcm, uses the plank edge with the top about web plate. screen is 80cm apart from ground level, and spread with sponge the below.With the screen horizontal positioned, mouse is put above that earlier, gently the one of which end is raised then; In 2s, this screen is become vertical position; Keep 5s, observe rat and whether can get off or live screen from screen with the fore paw grasping, thus evaluation fore paw grippage and muscular strength situation.Standards of grading are divided into 4 grades.
5 minutes: catch screen and climb;
4 minutes: in 5s, hold screen, can not fall down with fore paw;
3 minutes: temporarily hold screen, landing one segment distance, but do not fall down;
2 minutes: in 5s, fall down;
1 minute: when screen rotated, Mus fell down at once.
2.5.2 neural electrophysiology detects--h reflex
With reference to the method for Hefferan etc., use BL-420F to lead the biological function appearance more and detect, under the Patients Under Ketamine Anesthesia (100mg/kg/h, i.m.), right hind is fixed, pair of stimulating electrodes pin percutaneous insert tibial nerve around.Recording electrode places tibial tubercle to the internal malleolus mid point, and on the medial gastrocnemius, reference electrode places it, and heel string upper end is inboard down.
The h reflex record:
Stimulate tibial nerve (0.1 – 10mA in, 0.5 mA increments, 0.1Hz, 0.2ms with the square wave that increases stimulus intensity gradually; WPI; Isostim A320), by the coupled gear amplifier record of A/C result, carry out the mensuration of h reflex before treatment and after the treatment.Detect the Hmax/Mmax value.
2.5.3TTC method cerebral infarction scope is measured
The rat broken end is got brain, removes olfactory bulb, XIAONAO and low brain stem, and remainder is at-20 ℃ of freezing 10min of refrigerator; Crownly on ice pan be cut into 6, rapidly the brain sheet placed the TTC dye liquor, 37 ℃ of lucifuge temperature are incubated 1h; The non-ischemic region in dyed back is a rose, and infarct is a white.With computed in software cerebral infarction volume.
2.5.4HPLC fluorescence spectrometry rat brain spinal fluid excitatory neurotransmitter glutamic
1. sample collecting and processing: put to death animal behind the normal saline cardiac perfusion, draw cerebrospinal fluid with micro-feed liquor syringe needle, the centrifugal 15min of 10000g gets supernatant, and packing is to be measured in-80 ℃ of preservations.
2. the preparation of standard substance: the glutamic acid standard substance are made into the storing solution of 1mmol/L left and right sides concentration ,-20 ℃ of storages with 50% methanol.
3. the derive preparation and the derivatization reaction of liquid: 27mg OPA (OPA) is dissolved in the 0.5ml methanol; Adding 2 mercapto ethanol (2-M-CE) 20 μ l again adds 0.1mmol/L sodium tetraborate buffer (pH9.5) and makes the liquid of deriving to 5ml; The lucifuge room temperature preservation, available 1w.With 20 μ l titers or sample liquid and the 10 μ l liquid mixing of deriving, accurately react 90s, sample introduction 20 μ l before the last appearance.
4. mobile phase and elution requirement: mobile phase A: 100% methanol; Mobile phase B: pure water; Mobile phase C:25% methanol, 3% oxolane, 0.01mol/LPBSpH6.0; Mobile phase D:50% methanol, 0.01mol/LPBS pH6.0; Mobile phase all needs to use behind the ultrasonic degas through 0.45 μ m membrane filtration.Column temperature: 30 ℃, flow velocity: 1.0ml/min, excitation wavelength 340nm, emission wavelength 450nm.Earlier with the C post that balances each other; Then in 0 ~ 6min with C mutually linearity reduce in 20%, 6～23m in D is increased to 40% with A from 0 linearity in 80% linearity increase to 100%, 23 ~ 25min; D reduces to 60% from 100%; Use 20%A phase eluting in 25～25.50min instead, 25.51 ~ 27.00min increases to 100% with B from 80% linearity, uses 100%C at last instead and balances each other.So accomplish a circulation.
3 experimental results
3.1 neuroethology (Fig. 1)
Can be known that by Fig. 1 Fructus Trichosanthis guizhi decoction group is than model group, the scoring of the 5th, 6,7 day neural behavioristics significantly improves.(P＜0.05); Fig. 1 prompting was from after the modeling the 1st day to the 7th day, and two groups neuroethology scoring pro-did not all have significant difference (P＞0.05) in 4 days, but played the 7th day from the 5th day, model group and Fructus Trichosanthis guizhi decoction group exist significant difference (
*P＜0.05), the scoring of Fructus Trichosanthis guizhi decoction group neuroethology is superior to model group
3.2 screen experiment
Be used for testing rat muscular strength, muscular tension, endurance and balanced capacity.Can be known that by Fig. 2 Fructus Trichosanthis guizhi decoction group is than model group, screen experiment scoring in the 5th, 6,7 day significantly improves.（P＜0.05）
Fig. 2 prompting was from after the modeling the 1st day to the 7th day, and two groups screen test scoring pro-did not all have significant difference (P＞0.05) in 4 days, but played the 7th day from the 5th day, model group and Fructus Trichosanthis guizhi decoction group exist significant difference (
*P＜0.05), Fructus Trichosanthis guizhi decoction networking screen test scoring is superior to model group.
3.3TTC (Fig. 3)
The index of reaction cerebral infarction scope during TTC dyeing, wherein white is represented infarction tissue, the red not ischemic tissue that represents normally.Fig. 3 respectively organized the TTC Infarction volume on the 7th day relatively, can know that Fructus Trichosanthis guizhi decoction group is than model group, and Infarction volume is obviously dwindled.（P＜0.05）
Fig. 3 prompting, after modeling the 7th day, there were significant difference (P＜0.05) in model group and Fructus Trichosanthis guizhi decoction group Infarction volume, and Fructus Trichosanthis guizhi decoction group Infarction volume is significantly less than model group.
3.4H reflection (Fig. 4)
H reflex is the myoelectric index of reflection A-MN irritability and spasm.Hmax/Mmax increased after Fig. 4 showed modeling, and Fructus Trichosanthis guizhi decoction group can reduce the Hmax/Mmax value that increases.
Fig. 4 prompting, modeling is after 1 day, and Hmax/Mmax significantly increases (sham operated rats: 0.053 ± 0.001; Model group: 0.183 ± 0.008,
*P＜0.05, sham operated rats and model group are relatively; Fructus Trichosanthis guizhi decoction group: 0.172 ± 0.009,
*P＜0.05, Fructus Trichosanthis guizhi decoction group and sham operated rats are relatively).After 7 days, Fructus Trichosanthis guizhi decoction group Hmax/Mmax ratio significantly descend (#P＜0.05, Fructus Trichosanthis guizhi decoction group and model group are relatively).
3.5 glutamic (Fig. 5)
Excitatory amino acid-glutamic and spasm are proportionate in the cerebrospinal fluid.Can know that by Fig. 5 Fructus Trichosanthis guizhi decoction group compares with model group, can significantly reduce the glutamic acid that brings by the cerebral ischemia spasm and increase.
Fig. 5 prompting, modeling is after 7 days, and Glu content is in the sham operated rats cerebrospinal fluid: 201.16 ± 3.68mmol/L; Model group: 855.04 ± 13.20mmol/L; Fructus Trichosanthis guizhi decoction group: 222.97 ± 16.93mmol/L.
*Model group significantly increases than sham operated rats, and # treatment group significantly reduces (P＜0.05) than model group.
4 experiment conclusion
The Fructus Trichosanthis guizhi decoction can be marked through spasm rat nerves behavioristics after improving cerebral ischemia; Reduce Infarction volume; Increase muscular strength, muscular tension and coordinated balance ability; Regulate h reflex, aspects such as reduction rat brain spinal fluid excitatory amino acid-aminoglutaric acid concentration play the brain protection, reduce the effect of muscle spasm.
Limb spasm case after the Test Example 3 Drug therapy apoplexys of the present invention:
Lee man 60 years old is chief complaint with " unable 2 months of left limb ", and the concrete course of disease is following: " apoplexy " Western medicine diagnose before 2 months " right side basal ganglia region cerebral infarction ".Upper left limb spasm be carry on the arm basket, ankylosis, limitation of activity.Capable rehabilitation training one month is alleviated not obvious.Body is comparatively fat, xerostomia happiness drink, hyperhidrosis, receive can, still can sleep, stool partially firmly, delegation on the 2nd, red urine.The past hypertension history.Physical examination: the left side muscular tension is higher, hyperreflexia.Pathology is levied the positive.The dark yellow and thin fur floating pulse of light red tongue string.Dialectically be: disharmony of nutrient QI with defensive QI, blood stasis due to qi deficiency, the hepatic and renal YIN deficiency, the muscle arteries and veins loses supports.The prescription: 6 pieces of Radix Astragali 30g of Radix Trichosanthis 30g Ramulus Cinnamomi 12g Radix Paeoniae Alba 18g Radix Glycyrrhizae Preparata 6g Rhizoma Zingiberis Recens 6g Fructus Jujubae Semen Coicis 30g Rhizoma Atractylodis Macrocephalae 15g Radix Paeoniae Rubra 15g, xerostomia after medicine advances six doses, the hyperhidrosis transference cure, receive can, the peace of sleeping, two just the accent.The left limb spasm is slightly better before.Keep former side and continue into 15 doses, enjoin the patient to cooperate rehabilitation training simultaneously.Patient's left upper extremity spasm is alleviated basically.Elbow joint can stretch near 180 degree.Also make moderate progress on the function.
The rehabilitation training of treatment post-stroke limb spasm comprises modes such as adopting acupuncture, Chinese medicine.Medicine of the present invention is used to treat the post-stroke limb spasm, and drug effect is clear and definite, can increase the nerve excitability transmission, and the irritability transmission of nervus centralis is relevant with facilitation, and therefore, medicine of the present invention can play facilitation to rehabilitation training.
Claims (6)
1. contain the purposes of following raw materials by weight proportions in the medicine of preparation treatment post-stroke limb spasm:
Radix Trichosanthis 15-45 part, Ramulus Cinnamomi 4.5-13.5 part, Radix Paeoniae Alba 4.5-13.5 part, Radix Glycyrrhizae 3-9 part, Rhizoma Zingiberis Recens 4.5-13.5 part, Fructus Jujubae 6-18 part.
2. purposes according to claim 1 is characterized in that: described medicine is the medicine of treating post-stroke hemiplegia spasm and alleviating the obstacle of limb movement that is caused by spasm.
3. purposes according to claim 1 and 2 is characterized in that: described medicine is the preparation that is prepared from following raw materials by weight proportions:
30 parts of Radix Trichosanthis, 9 parts of Ramulus Cinnamomi, 9 parts of the Radix Paeoniae Albas, 6 parts in Radix Glycyrrhizae, 9 parts in Rhizoma Zingiberis Recens, 12 parts in Fructus Jujubae.
4. according to any described purposes of claim 1-3; It is characterized in that: described medicine is the protogenic medicinal powder by Radix Trichosanthis, Ramulus Cinnamomi, the Radix Paeoniae Alba, Radix Glycyrrhizae, Rhizoma Zingiberis Recens, Fructus Jujubae; Or water or extractive with organic solvent be active component, adds the preparation that acceptable accessories or complementary composition are prepared from.
5. purposes according to claim 4 is characterized in that: described preparation is tablet, granule, oral liquid, capsule, pill.
6. according to any described purposes of claim 1-5, it is characterized in that: the method for preparing of described medicine comprises the steps:
A, take by weighing each materials of weight proportions medicine;
B, the Radix Paeoniae Alba are ground into fine powder, sieve;
C, get Ramulus Cinnamomi, Rhizoma Zingiberis Recens water vapour distillation volatile oil, subsequent use;
D, Radix Trichosanthis, Radix Glycyrrhizae, Fructus Jujubae, Ramulus Cinnamomi, the decocte with water of Rhizoma Zingiberis Recens medicinal residues after the c step is extracted are filtered, and filtrating is condensed into clear paste; Add the Radix Paeoniae Alba fine powder of b step preparation, the volatile oil of c step in the clear paste, mixing adds acceptable accessories or complementary composition, is prepared into preparation pharmaceutically commonly used.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104215707A (en) * | 2014-09-02 | 2014-12-17 | 福建中医药大学 | Quality inspection method of trichosanthes kirilowii-ramuli cinnamomi decoction |
| CN104225524A (en) * | 2014-09-02 | 2014-12-24 | 福建中医药大学 | Application of trichosanthes kirilowii maxim and cassia twig decoction in preparing medicament for treating or/and preventing cognitive impairment |
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| CN111481655A (en) * | 2020-06-09 | 2020-08-04 | 河南省中医院（河南中医药大学第二附属医院） | External fumigation-washing traditional Chinese medicine composition for treating post-stroke myotonia increase |
| CN114869956A (en) * | 2022-02-11 | 2022-08-09 | 福建中医药大学附属人民医院（福建省人民医院） | Pharmaceutical composition for treating post-stroke motor dysfunction and preparation method and application thereof |
| CN114869956B (en) * | 2022-02-11 | 2023-09-22 | 福建中医药大学附属人民医院（福建省人民医院） | Pharmaceutical composition for treating post-stroke dyskinesia, and preparation method and application thereof |
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