TWI794335B - Use of Pien Tze Huang and its preparations in the treatment of sequelae of cerebral apoplexy - Google Patents

Abstract

The invention belongs to the field of traditional Chinese medicines, and in particular relates to the use of Pien Tze Huang and its preparations in treating sequelae of cerebral apoplexy. The present invention finds through research that Pien Tze Huang has comprehensive effects such as improving abnormal blood rheology, energy metabolism disorder in brain tissue, and neurological dysfunction in model rats with sequelae of cerebral apoplexy, and can promote the recovery of damaged brain cells in model rats to a certain extent. Recovery, and then restore the control function of the lower nerve and muscle function, so it has a good therapeutic effect on the sequelae of stroke.

Description

Use of Pien Tze Huang and its preparations in the treatment of sequelae of cerebral apoplexy

The present invention belongs to the field of traditional Chinese medicine; more specifically, it refers to the application of Pien Tze Huang and its preparation in treating sequelae of cerebral apoplexy.

Sequelae of cerebral apoplexy refers to symptoms such as hemiplegia, dysphasia of speech, crooked mouth and eyes left over after 6 months of stroke treatment. The root causes of the above symptoms are: high blood viscosity, high blood lipids, high blood pressure, high blood sugar, platelet aggregation and other blood lesions inside the cerebrovascular, and vascular lesions such as atherosclerotic plaque formation, which are the result of the joint action of the two lesions The formed thrombus blocks the cerebral artery, leading to the interruption of blood flow in the brain and the necrosis of brain tissue due to ischemia and hypoxia. The post-stroke sequelae are also called the post-stroke sequelae period. Compared with the recovery period, the recovery speed and degree are slower. Although after standardized treatment in the acute and convalescent stages of stroke, the condition of most stroke patients can be effectively controlled and their functions recovered to a certain extent, but the patients still have disabilities of varying degrees, of which up to 40% are severely disabled. If patients with stroke sequelae take good treatment measures within 2-3 years, it is expected to improve the functional impairment of the patients, thereby improving the quality of life of the patients.

At present, the effective way to improve the symptoms of stroke sequelae and reduce the high recurrence rate is mainly to combine scientific diet and active and passive recovery exercises, combined with drug treatment, which can not only treat stroke-induced atherosclerotic plaque formation, high blood viscosity, etc. Effective treatment of basic lesions can prevent the re-formation of arteriosclerotic thrombus; it can also improve the blood supply and oxygen supply of brain tissue, create a good internal environment for brain tissue, restore the brain nervous system, and then make it control the movement, Speech neurological signs improved. Drugs to improve the symptoms of stroke sequelae mainly include: traditional Chinese medicine treatment, western medicine treatment, and integrated traditional Chinese and western medicine treatment. Among them, traditional Chinese medicine treatment includes three methods: blood circulation promoting and blood stasis treatment, aroma resuscitation treatment, and blood circulation promoting and blood stasis rejuvenation, aroma resuscitation dual treatment.

Pien Tze Huang is a national first-class protected variety of traditional Chinese medicine. It is refined from precious Chinese medicines such as musk, bezoar, snake gall, and Panax notoginseng. Hepatitis, bronchitis, malignant tumors and other diseases.

Although there are literature reports in the prior art that the preventive treatment of Pien Tze Huang can reduce the severity of stroke and prolong the survival time of stroke; however, there is no relevant report on the use of Pien Tze Huang and its preparations for the treatment of stroke sequelae.

For this reason, the present invention proposes the application of Pien Tze Huang and its preparations in the treatment of sequelae of cerebral apoplexy.

In order to solve the above-mentioned technical problems, the present invention is achieved through the following technical solutions: the main purpose of the present invention is to provide the application of Pien Tze Huang and its preparation in the medicine for treating sequelae of cerebral apoplexy.

According to the above-mentioned purposes, the present invention treats sequelae of cerebral apoplexy refers to: improving abnormal blood rheology.

Said use, improving abnormal blood rheology means: reducing at least one of the following hemorheology indexes: whole blood viscosity, plasma viscosity, red blood cell deformation index, hematocrit and platelet maximum aggregation rate.

Said use, treating sequelae of cerebral apoplexy refers to: improving energy metabolism disorder in brain tissue.

Said use, improving energy metabolism disorder in brain tissue means: increasing the content of at least one of the following energy metabolism indicators in brain tissue: adenosine triphosphate and adenosine diphosphate.

Said use, treating sequelae of cerebral apoplexy refers to: improving neurological dysfunction.

Said use, improving neurological dysfunction means: increasing the content of at least one of the following neurological function indicators in brain tissue: norepinephrine, dopamine and 5-hydroxytryptamine.

For said purposes, Pien Tze Huang is added with conventional auxiliary materials to make clinically acceptable preparations.

The pharmaceutically acceptable auxiliary materials are: fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, preservatives, bases and the like. Fillers include: starch, pregelatinized starch, lactose, mannitol, chitin, microcrystalline cellulose, sucrose, etc.; disintegrants include: starch, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, Cross-linked polyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, croscarmellose sodium, etc.; lubricants include: magnesium stearate, sodium lauryl sulfate, talc, silicon dioxide, etc.; suspending agent Including: polyvinylpyrrolidone, microcrystalline cellulose, sucrose, agar, hydroxypropyl methylcellulose, etc.; binders include starch slurry, polyvinylpyrrolidone, hydroxypropylmethylcellulose, etc.; sweeteners include: saccharin Sodium, aspartame, sucrose, cyclamate, glycyrrhetinic acid, etc.; flavoring agents include: sweeteners and various essences; preservatives include: parabens, benzoic acid, sodium benzoate, sorbic acid and its salts, Benzalkonium bromide, chlorhexidine acetate, eucalyptus oil, etc.; substrates include: PEG6000, PEG4000, insect wax, etc.

For the above use, the preparation is selected from lozenges, tablets, capsules, granules, powders, pills, tinctures, liquors, decoctions or mixtures.

For the above application, each administration of the Pien Tze Huang preparation contains 0.3-0.9 g of Pien Tze Huang.

Compared with the prior art, the above-mentioned technical solution of the present invention has the following advantages: the present invention has found through research that Pien Tze Huang has comprehensive effects such as improving abnormal blood rheology, energy metabolism disorder in brain tissue and neurological dysfunction in model rats with sequelae of cerebral apoplexy, and It can promote the recovery of damaged brain cells in model rats to a certain extent, and then restore the The dominance function of the lower nerve and muscle function, so it has a good therapeutic effect on the sequelae of cerebral apoplexy.

In order to allow a more detailed understanding of the purpose, function, features and structure of the present invention, the preferred embodiments are described below with accompanying drawings.

In the following examples and experimental examples of the present invention, Pien Tze Huang is produced by Zhangzhou Pien Tze Huang Pharmaceutical Co., Ltd.

Example 1 Pien Tze Huang is made into clinically acceptable lozenges by adding conventional auxiliary materials according to conventional procedures.

Example 2 Pien Tze Huang was made into clinically acceptable tablets according to the conventional manufacturing process and conventional auxiliary materials were added.

Example 3 Pien Tze Huang was made into clinically acceptable capsules by adding conventional auxiliary materials according to the conventional manufacturing process.

Example 4 Pien Tze Huang was made into clinically acceptable granules according to the conventional manufacturing process and conventional auxiliary materials were added.

Experimental Example 1 Study on the therapeutic effect of Pien Tze Huang on sequelae of cerebral apoplexy

1. Purpose of the experiment

To study the therapeutic effect of Pien Tze Huang on sequelae of cerebral apoplexy.

2. Experimental method

2.1 Experimental animals

Male Wistar rats, 12 weeks old, weighing 250±25g, 50 in total.

2.2 Experimental Instruments

PA-3210 Platelet Aggregator, LBY-N6K Automatic Cleaning Rotational Viscometer, LG-B190 Red Blood Cell Deformation Instrument, Agilent High Performance Liquid Chromatography System (SPD-10AV UV Detector, L-ECD-6A Electrochemical Detector).

2.3 Drugs to be tested

Pien Tze Huang was crushed into fine powder with a grinder as the test drug.

2.4 Experimental grouping

50 male Wistar rats were randomly divided into normal control group, model control group, low-dose group, middle-dose group and high-dose group, with 10 animals in each group.

2.5 Establishment of cerebral apoplexy sequela model and administration method

After the rat was anesthetized, an incision was made in the middle of the neck, the left common carotid artery was ligated first, and then the right common carotid artery was clamped, and released after 1 hour. Make an incision on the top to expose the skull, drill a bone window with a diameter of about 2mm, and coagulate the middle cerebral artery with a micro-coagulation knife. 24 hours after the operation, use a random electric pulse random stimulator for rats, and the stimulation intensity is 50-80V, 0.5- 25Hz, 0.1-1.1ms, after 30 days, evaluate whether the model is successfully established with reference to the Zealonga scoring method.

After confirming the successful establishment of the stroke sequelae model, the drug was started 30 days after the operation. The low-dose group was given 0.7g/kg Pien Tze Huang by intragastric administration, the middle-dose group was given 1.4g/kg Pien Tze Huang by intragastric administration, and the high-dose group was given 2.1g Pien Tze Huang by intragastric administration. Pien Tze Huang per kg, the volume of intragastric administration in the above three groups was 20mL/(kg.d); the normal control group and the model control group were given the same amount of normal saline by intragastric administration. Each group was administered continuously for 15 days.

2.6 Neurological deficit score

Referring to the Zealonga scoring method, the rats in each group were scored on a 5-point scale 30 days after surgery. The specific scoring criteria are as follows: 0 points: no symptoms of nerve injury; 1 point: unable to fully straighten the contralateral front paw; 2 points: turning to the outside; 3 points: falling to the opposite side; 4 points: unable to walk spontaneously, conscious lost. A score of 1-4 indicates a successful model.

2.7 Determination of hemorheology indexes

Blood was collected from the abdominal aorta of the rats after gavage for 15 days, and the viscosity of whole blood at three shear rates of 10s ^-1 , 50s ^-1 , and 200 ^-1 at 37°C and the viscosity of plasma at 100s ^-1 were measured with a blood viscosity tester; The maximum deformation index of red blood cells is measured by the red blood cell deformation instrument; the hematocrit of red blood cells is measured by micro high-speed centrifugation.

2.8 Determination of platelet aggregation rate

Blood was collected from the abdominal aorta, anticoagulated with sodium citrate solution (volume ratio 1:9), centrifuged at 1000r/min for 10min to prepare platelet-rich plasma (PRP), and a certain amount was taken for later use. Then centrifuge the remaining part at 3000r/min for 15min to prepare platelet-poor plasma (PPP), mix PRP and PPP in a certain proportion, and adjust the light transmittance to about 4000 with a platelet analyzer (the number of platelets at this time is 3×9 ¹² /L), using adenosine diphosphate as an inducer, the maximum aggregation rate of platelet aggregation in a certain period of time was determined by turbidimetry.

2.9 Determination of the content of adenosine triphosphate and adenosine diphosphate in brain cells

(1) Sample pretreatment

After the rats were sacrificed, the right brain tissue was taken and weighed, and 2 mL of 0.4 mol/L acetonitrile was quickly added, the tissue was completely homogeneously mixed, placed in an ice bath for 30 min, centrifuged at 10,000 rpm for 10 min, and the supernatant was taken, centrifuged at 3,000 rpm for 5 min, and the supernatant was taken solution, filtered through a membrane with a pore size of 0.22 μm, and stored at -86°C until testing.

(2) Chromatographic conditions

SPD-10AV UV detector, mobile phase 0.05mol/L NH ₄ H ₂ PO ₄ buffer (pH6.0), flow rate 1.6mL/min, column temperature 25°C, detection wavelength 254nm.

2.10 Determination of neurotransmitter content in brain tissue

(1) Sample pretreatment

The right brain tissue of the rat was taken and weighed, quickly added to 2ml of ice-cold 0.05mol/L perchloric acid solution (containing 0.4g/L sodium metabisulfite and 0.4g/L EDTA), and mixed evenly in an ice bath for 1min, 4 Centrifuge at 15,000 rpm for 30 min at ℃, take the supernatant, filter, store at -86 ℃, and wait for testing.

(2) Chromatographic conditions

L-ECD-6A electrochemical detector, the mobile phase is a mixture of 80mmol/L NH ₄ H ₂ PO ₄ and 60mmol/L citric acid buffer and methanol (8:2), pH3.4, flow rate 0.6mL/min .

3. Experimental results

3.1 Observation of general signs

Compared with the normal control group, after modeling, the rats in each group had symptoms of hemiplegia, manifested as dull hair, listlessness, drowsiness, decreased food intake and drinking water, adduction of the left upper limb, physical, and when climbing the cage. The body is tilted to one side, the lower limbs are abducted, and it is difficult to adduct them. When walking or jumping, the rats are in a limp state. The size of the lateral testicles is different.

After administration, it was observed in the low-dose group, middle-dose group and high-dose group that the symptoms of hemiplegia of the model rats were improved to varying degrees, and there were phenomena such as moist hair, increased activity intensity, improved diet, and accelerated wound healing.

3.2 Neurological deficit score

The neurological deficit scores of each group are shown in Table 1.

As can be seen from Table 1: (1) the score of the model control group is significantly higher than that of the normal control group (p<0.01), which shows that: the model of sequelae of cerebral apoplexy is successfully established, and the rats have sequelae after neurological impairment; (2) 30 days after operation, the scores of the low-dose group, middle-dose group, and high-dose group of each administration group were significantly lower than those of the model control group (p<0.05), which indicated that Pien Tze Huang can improve the stroke sequelae model Rat neurological function is conducive to the recovery of its neurological function; (3) the order of scoring of each administration group is successively (from high to low): low dosage group, middle dosage group, high dosage group, this shows: in certain Within the dosage range, with the increase of the dosage of Pien Tze Huang, the neurological deficit score tended to decrease.

3.3 Effects on the hemorheology of rats

Table 2 shows the experimental results of hemorheology in each group of rats.

It can be seen from Table 2: (1) Compared with the normal control group, the whole blood viscosity, plasma viscosity, hematocrit, platelet maximum aggregation rate and other indicators of the model control group were significantly increased (p<0.05); (2) Compared with the model control group, the whole blood viscosity, plasma viscosity, hematocrit, platelet maximum aggregation rate and other indicators in each administration group were all decreased to a certain extent, among which the whole blood viscosity, Plasma viscosity and maximum aggregation rate of platelets were significantly reduced (p<0.05); this indicated that Pien Tze Huang could improve the hemorrheology of stroke sequelae model rats.

3.4 Effects on Energy Metabolism in Rat Brain Tissue

The contents of adenosine triphosphate and adenosine diphosphate in the brain tissue of rats in each group are shown in Table 3 Show.

As can be seen from Table 3: (1) the contents of adenosine triphosphate and adenosine diphosphate in the brain tissue of the rats in the model control group were significantly lower than those of the normal control group. (p<0.001); (2) the contents of adenosine triphosphate and adenosine diphosphate in the brain tissue of rats in each administration group were significantly higher than those of adenosine triphosphate and adenosine diphosphate in the brain tissue of the model control group. Adenosine diphosphate content (p<0.001 or p<0.01); This shows that: Pien Tze Huang can increase the adenine nucleoside triphosphate and adenine nucleoside diphosphate content in the cerebral tissue of model rats with sequelae of cerebral apoplexy, can improve Energy metabolism disorder caused by stroke.

3.5 Effects on neurotransmitters in rat brain tissue

The contents of NE, DA and 5-HT in the brain tissue of rats in each group are shown in Table 4.

It can be seen from Table 4 that: (1) the contents of NE, DA and 5-HT in the brain tissue of rats in the model control group were significantly lower than those of NE, DA and 5-HT in the brain tissues of the rats in the normal control group (p<0.001 or p<0.01); (2) The contents of NE, DA and 5-HT in the brain tissue of rats in each administration group were all increased to varying degrees, and the elevation of NE contents in each administration group was comparable to that in the model control group. Compared with significant difference (p<0.01), the increase of DA and 5-HT content in middle and high dose groups has significant difference (p<0.05) compared with model control group DA, 5-HT content; It shows that Pien Tze Huang can promote the damage repair of neurons in rat model rats with sequelae of cerebral apoplexy, and can improve the neurological dysfunction of brain tissue.

4. Experimental conclusion

In summary, Pien Tze Huang can improve the comprehensive effects of abnormal blood rheology, energy metabolism disorder in brain tissue and neurological dysfunction in model rats with sequelae of cerebral apoplexy, and can promote the recovery of damaged brain cells in model rats to a certain extent. It restores the dominance function to the lower nerves and muscles, so it has a good therapeutic effect on the sequelae of cerebral apoplexy.

However, the above-mentioned embodiments are only examples for clearly illustrating, rather than limiting the implementation. For those of ordinary skill in the art, other changes or changes in different forms can be made on the basis of the above description. It is not necessary and impossible to exhaustively list all the implementation manners here. The obvious changes or changes derived therefrom should be included in the scope of the patent application of the present invention.

Therefore, the present invention has excellent advancement and practicability among similar products. At the same time, after searching domestic and foreign technical documents about this type, it is true that no identical or similar structure or technology exists before the application of this case. Therefore, This case should meet the patent requirements of "inventiveness", "suitability for industrial utilization" and "progressiveness", and the application should be filed according to law.

Claims (4)

A use of Pien Tze Huang and its preparations in the preparation of medicines for the treatment of stroke sequelae, wherein the treatment of stroke sequelae refers to improving abnormal blood rheology and improving energy metabolism disorders in brain tissue, wherein the improvement of abnormal blood rheology refers to reducing the following: At least one of hemorheology indicators: whole blood viscosity, plasma viscosity, red blood cell deformation index, hematocrit and platelet maximum aggregation rate, the improvement of energy metabolism disorders in brain tissue refers to: increase at least one of the following in brain tissue The content in the energy metabolism index: adenosine triphosphate and adenosine diphosphate, and the Pien Tze Huang preparation contains 0.3-0.9 g of Pien Tze Huang in each dosage preparation. The use as described in Claim 1, wherein Pien Tze Huang is added with conventional excipients and prepared into clinically acceptable preparations according to conventional procedures. The use as described in claim 2, wherein the preparation is selected from lozenges, tablets, capsules, granules, powders, pills, tinctures, liquors, decoctions or mixtures. A use of Pien Tze Huang or a composition containing Pien Tze Huang in the preparation of Pien Tze Huang medicine for treating sequelae of cerebral apoplexy, wherein the Pien Tze Huang medicine includes Pien Tze Huang or a composition containing Pien Tze Huang, wherein the treatment of sequelae of cerebral apoplexy refers to improving abnormal blood rheology and Improving energy metabolism disorders in brain tissue, wherein the improvement of abnormal blood rheology refers to reducing at least one of the following hemorheology indicators: whole blood viscosity, plasma viscosity, red blood cell deformation index, hematocrit and maximum platelet aggregation rate ,and The improvement of energy metabolism disorder in brain tissue refers to: increasing the content of at least one of the following energy metabolism indicators in brain tissue: adenosine triphosphate and adenosine diphosphate.