A Chinese medicine composition and a medicine combination for treating cerebral palsy

Abstract

The invention provides a Chinese medicine composition and a drug combination for treating cerebral palsy, comprising 2-3 parts of French pinellia, 1-3 parts of cooked rhubarb, 4-6 parts of red beans, 4-6 parts of light fermented black beans, 2-4 parts of platycodon, 5-7 parts of thunbergii, 3-5 parts of stir-fried bitter almonds, 2-4 parts of ginger magnolia bark and 3-5 parts of scutellaria. The Chinese medicine composition is created based on Guati powder and Sanwu Baisan in Treatise on Febrile Diseases, toxic drugs in the above two prescriptions are removed, and the remaining medicinal flavors are retained, so the safety is extremely high; the Chinese medicine composition can achieve a drug effect equivalent to that of nerve growth factor when used alone, significantly reducing the cost of treatment, and can significantly improve the efficacy of treating cerebral palsy when used in combination with nerve growth factor.

Description

Technical Field

[0001] The present invention relates to the technical field of drug combinations, and in particular to a traditional Chinese medicine composition and a drug combination for treating cerebral palsy. Background Art

[0002] At present, in addition to rehabilitation training, the domestic treatment of cerebral palsy generally uses nerve growth factor injections, or some patients seek help from traditional Chinese medicine massage or Chinese medicine, which has a certain effect. However, in clinical practice, patients need rehabilitation training for several years or the cost of nerve growth factor injection is expensive. At the same time, a large number of patients develop side effects such as precocious puberty after taking tonic Chinese and Western medicines. For those who seek help from Chinese medicine, there are problems such as differences in medication and low efficiency due to different prescriptions for each patient. Therefore, the current domestic treatment of cerebral palsy has problems such as long treatment cycle, unstable efficacy, high cost and side effects. Summary of the invention

[0003] The purpose of the present invention is to provide a Chinese medicine composition and a composition for treating cerebral palsy, thereby solving the above-mentioned problems existing in the prior art.

[0004] In order to achieve the above object, the technical solution adopted by the present invention is as follows:

[0005] In a first aspect, the present invention provides a traditional Chinese medicine composition, comprising, by weight, 2-3 parts of French pinellia, 1-3 parts of cooked rhubarb, 4-6 parts of adzuki beans, 4-6 parts of light fermented black beans, 2-4 parts of platycodon, 5-7 parts of thunbergii, 3-5 parts of stir-fried bitter almonds, 2-4 parts of ginger magnolia bark and 3-5 parts of scutellaria baicalensis.

[0006] Preferably, the Chinese medicine composition comprises, by weight, 3 parts of French pinellia, 2 parts of cooked rhubarb, 5 parts of adzuki beans, 6 parts of light fermented black beans, 3 parts of platycodon, 6 parts of thunbergii bulbs, 5 parts of stir-fried bitter almonds, 2 parts of ginger magnolia bark and 4 parts of scutellaria baicalensis.

[0007] In a second aspect, the present invention provides a drug combination for treating cerebral palsy, comprising the Chinese medicine composition described in the first aspect, and nerve growth factor.

[0008] Preferably, the preparation of the traditional Chinese medicine composition includes one of tablets, dispersants, soft capsules, granules, pills, pellets, gels and oral liquid preparations.

[0009] The beneficial effects of the present invention are:

[0010] The invention provides a traditional Chinese medicine composition and a drug combination for treating cerebral palsy. The traditional Chinese medicine composition is created based on Guati San and Sanwu Bai San in Treatise on Febrile Diseases, and the toxic drugs in the two prescriptions are removed, while the remaining medicinal flavors are retained, so the safety is extremely high. The traditional Chinese medicine composition can achieve a drug effect equivalent to that of nerve growth factor when used alone, significantly reducing the cost of treatment. When used in combination with nerve growth factor as a new drug combination, the efficacy of treating cerebral palsy can be significantly improved. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Figure 1 This is a diagram of the mouse experiment design;

[0012] Figure 2 This is a line graph of behavioral index scores of offspring born by pregnant mice in the normal group and the model group;

[0013] Figure 3 This is the bar graph of the tensile force measurement of the normal group and the model group;

[0014] Figure 4 This is the line graph of the body weight of the normal group and the model group;

[0015] Figure 5 It is a line graph of the body weight of each group of animals during the drug administration period, Figure a is a line graph of the body weight of each group of male animals, and Figure b is a line graph of the body weight of each group of female animals;

[0016] Figure 6 It is a line graph of the time spent on the pole by each group of animals during the drug administration period, wherein Figure a is a line graph of the time spent on the pole by each group of male animals, and Figure b is a line graph of the time spent on the pole by each group of female animals;

[0017] Figure 7 It is a line graph of the pulling force values ​​of animals in each group during the drug administration period, wherein Figure a is a line graph of the pulling force values ​​of male animals in each group, and Figure b is a line graph of the pulling force values ​​of female animals in each group;

[0018] Figure 8 It is a line graph of organ index of each group of animals, wherein Figure a is a line graph of pulling force value of each group of male animals, and Figure b is a line graph of pulling force value of each group of female animals;

[0019] Fig. 9 is the TTC staining image of the brain sections of animals in each group; DETAILED DESCRIPTION

[0020] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings. It should be understood that the specific implementation methods described herein are only used to explain the present invention and are not used to limit the present invention.

[0021] As a traditional Chinese medicine work, Treatise on Febrile Diseases records many famous prescriptions, including the composition records of Guati Powder, Sanwu Bai Powder and Daxianxiong Pills. The composition of Guati Powder is Dandouchi, Red Bean and Guati. Guati is poisonous and can induce vomiting; Dandouchi and Red Bean have mild properties. As auxiliary drugs to speed up the body's metabolism, they can enhance the positive effects of Guati poison and reduce the side effects of Guati poison. Similarly, the composition of Sanwu Bai Powder is Platycodon, Fritillaria and Croton. Croton is poisonous and can cause vomiting and diarrhea. Platycodon and Fritillaria have mild properties. As auxiliary drugs to speed up the body's metabolism, they can enhance the positive effects of Croton poison and reduce the side effects of Croton poison. Daxianxiong Pills are composed of rhubarb, mirabilite, gansui, tinglizi and fried bitter almonds. Gansui is poisonous and can cause vomiting and diarrhea; tinglizi, fried bitter almonds and rhubarb are relatively safe. Toxic drug ingredients may cause harm to the human body during use, so the toxic ingredients are removed, the safe ingredients are retained and the content of all components is adjusted to obtain a new Chinese medicine composition that uses common medicinal materials to achieve a tonic effect.

[0022] The nerve growth factor in Western medicine is used to treat cerebral palsy (brain damage), assisted by the Chinese medicine composition provided in the present invention, so that the treatment effect is optimized.

[0023] Example 1

[0024] This embodiment provides a composition for auxiliary treatment of cerebral palsy, including 6g of Pinellia ternata, 4g of cooked Rhubarb, 10g of Adzuki Bean, 12g of Fructus Sojae Indici, 6g of Platycodon Grandiflorum, 12g of Fritillaria Thunbergii, 10g of stir-fried Apricot Kernel, 4g of Magnolia officinalis and 8g of Lemongrass Seed.

[0025] Example 2

[0026] This embodiment provides a composition for auxiliary treatment of cerebral palsy, including 4g of French pinellia, 2g of cooked rhubarb, 8g of red bean, 8g of light fermented black beans, 4g of platycodon, 10g of thunbergii, 6g of stir-fried bitter almonds, 6g of ginger magnolia bark and 6g of scutellaria baicalensis.

[0027] Example 3

[0028] This embodiment provides a composition for auxiliary treatment of cerebral palsy, including 4g of French pinellia, 6g of cooked rhubarb, 12g of red bean, 10g of light black bean, 8g of platycodon, 14g of thunbergii, 8g of stir-fried bitter almond, 8g of ginger magnolia bark and 10g of scutellaria baicalensis.

[0029] Example 4

[0030] This embodiment provides a combination drug for treating cerebral palsy, comprising the Chinese medicine composition described in any one of Embodiments 1-3, and further comprising nerve growth factor.

[0031] The preparation method of the medicament prepared by boiling the composition for auxiliary treatment of cerebral palsy described in any one of Examples 1-3 is as follows:

[0032] (1) Soaking the composition: put the composition into a container and add 350 ml of water to soak for 15 minutes;

[0033] (2) Decoction: Place the container on the induction cooker and select the hot pot mode;

[0034] A. Fry over high heat (2200W) for 1 minute;

[0035] B. Change to medium heat (300W) and fry for 3 minutes;

[0036] C. Cover the lid and fry for 20 minutes on low heat (120W) - open the lid and fry for 20 minutes;

[0037] D. Filtration;

[0038] E. Transfer to a 50ml centrifuge tube and confirm the volume (about 20ml)

[0039] (3) Secondary decoction: Add 100 ml of water into the container, boil over medium heat (300 W) for 2 min, then turn to low heat (120 W) for 20 min;

[0040] (4) Filtration, same steps as above;

[0041] (5) The two decoctions were mixed (about 40 ml), cooled, and stored at 4°C to obtain a combined decoction of the drug.

[0042] Nerve growth factor is dissolved in sterile water for injection, and each vial is dissolved in 2 ml of sterile water for injection.

[0043] When used, the volume ratio of the important composition to the dissolved nerve growth factor is 10:1.

[0044] Example 5

[0045] The present embodiment provides a newborn mouse brain injury experiment. In this experiment, a newborn mouse brain injury model caused by intrauterine hypoxia in pregnant mice is established, and the effect of the model is evaluated. The Chinese medicine composition provided in Example 1 is orally administered to the model mice as a test drug for 28 days, and nerve growth factor is simultaneously administered as a positive drug for comparison, as well as the combination drug provided in Example 4. The improvement effect of the test drug and the positive drug on the brain injury of newborn mice caused by intrauterine hypoxia is observed through biological indicators and behavioral observations, providing a theoretical basis for clinical treatment.

[0046] 1. Experimental Materials

[0047] 1. Experimental Animals

[0048] 16 ICR pregnant mice, 6-8 weeks old

[0049] 2. Experimental Reagents

[0050] Chloral hydrate (Fuchen Chemical Reagent Co., Ltd., 20190302), sterile water for injection (Shijiao Yinhu Pharmaceutical Co., Ltd., 5922041131), test drug (Plantagodendron and Douchi Decoction provided in Example 1), positive drug (mouse nerve growth factor for injection, Unnamed Biopharmaceutical Co., Ltd., 20220501), TTC (Beijing Solarbio Science, T8170)

[0051] 3. Experimental instruments

[0052] Weight scale (Harbin Huizhong Weighing Instrument Co., Ltd., JCS-11002C);

[0053] Electronic balance (Ohaus Instrument Co., Ltd., AR224CN);

[0054] Homemade transparent hypoxia device

[0055] Digital push-pull force gauge (Shanghai Siwei Instrument Manufacturing Co., Ltd., ZMF-50)

[0056] Mold incubator (Jinan Xinbeisi Biotechnology Co., Ltd., 02111905)

[0057] 2. Experimental process

[0058] 1. Experimental Design

[0059] The whole experimental process is as follows Figure 1 As shown, it includes preliminary experiments and formal experiments. The preliminary experiment is used to explore an animal model of neonatal brain injury that is close to clinical practice, to explore the pathogenesis of brain injury caused by intrauterine hypoxia, and to evaluate the effect of the model using evaluation indicators. The formal experiment uses the modeling method of the preliminary experiment. After establishing a brain injury model caused by intrauterine hypoxia, the test drug, the positive drug, and the combined use of the test drug and the positive drug are administered. Through the detection of behavioral indicators, the collection of behavioral videos, and the results of TTC staining of the animal brain, the efficacy of the test drug is evaluated, providing an experimental basis for the treatment of brain injury with traditional Chinese medicine.

[0060] 2. Preliminary Experiment

[0061] 2.1 The first experimental exploration of the model of neonatal brain damage caused by intrauterine hypoxia in mice

[0062] 1) Experimental process

[0063] Pregnant mice No. 1 and No. 2 were subjected to hypoxia experiments on the 15th day of pregnancy. The two pregnant mice were placed in a transparent hypoxia device, and hypoxia lasted for 10 minutes, followed by reoxygenation for 5 minutes, for a total of 5 rounds. The pups were subjected to hypoxia experiments every other day starting from the 10th day after birth, for 5 rounds each time, with hypoxia lasting 10 minutes and reoxygenation for 5 minutes.

[0064] 2) Index detection

[0065] (1) Pregnant mouse production indicators: number of days to delivery, whether there are stillbirths after delivery (survival rate), and number of babies born per litter.

[0066] (2) Newborn mice (pre-weaning period): age at eye opening, body weight on birth day, and skin color at birth; newborn mice were weighed once a week until weaning.

[0067] (3) Behavioral experiments and scoring were performed on newborn mice on days 14 and 21 after birth (Table 1).

[0068] Table 1 Behavioral index scoring standard table

[0069]

[0070]

[0071] Model establishment judgment:

[0072] When pregnant mice give birth prematurely, their pups die after birth, less than 10 animals survive each litter, and their pups open their eyes later than 14 days old, it is judged that the mother has successfully suffered from hypoxia. 21 days after the pups are born, if the sum of the three behavioral scores is higher than 6 points, it is judged that the pups have successfully suffered from hypoxia. The higher the score, the more severe the brain damage.

[0073] 3) Experimental results

[0074] (1) Analysis of routine indicators: Pregnant mouse No. 1 gave birth to 15 pups on the 19th day of pregnancy (2 days premature). There was no abnormality in the skin color of the pups, nor in their growth. All of them opened their eyes on the 16th day after birth, and no fetuses were stillborn. Therefore, the hypoxia experiment with mother mouse No. 1 was not successful. Pregnant mouse No. 2 gave birth to 10 pups on the 19th day of pregnancy (2 days premature). There was no abnormality in the skin color of the pups, nor in their growth. All of them opened their eyes on the 15th day after birth, and no fetuses were stillborn. Therefore, the hypoxia experiment with mother mouse No. 2 was not successful.

[0075] (2) Analysis of behavioral indicators: As shown in Table 2, when the pups born to pregnant mouse No. 1 were 21 days old, the sum of the three behavioral scores did not reach 6 points, so the hypoxia of the pups born to pregnant mouse No. 1 was not successful; when the pups born to pregnant mouse No. 2 were 21 days old, the sum of the three behavioral scores was 6.1 points, so the hypoxia of the pups born to pregnant mouse No. 2 was successful.

[0076] Table 2 Behavioral index score table of offspring born by pregnant mice No. 1 and No. 2

[0077]

[0078] Note: Due to the large differences in the number of offspring produced by the animals, no statistical analysis was performed.

[0079] 2.2 Second exploratory experiment on the neonatal mouse brain injury model induced by intrauterine hypoxia

[0080] 1) Based on the results of the first exploratory experiment, the conditions of the hypoxia experiment for pregnant mouse No. 3 were optimized. Starting from the 10th day of pregnancy, pregnant mouse No. 3 was subjected to a hypoxia experiment every other day for 5 rounds, each round of hypoxia for 10 minutes and reoxygenation for 5 minutes. Then, on the 14th day of pregnancy, a hypoxia experiment was conducted every day for 5 rounds, each round of hypoxia for 10 minutes and reoxygenation for 5 minutes until delivery.

[0081] According to the reaction of the offspring found in the first experiment, a new attempt was made on the hypoxia method of the offspring born by pregnant mouse No. 3: the offspring were divided into two groups. One group continued the hypoxia method of the first offspring. From the 10th day after the offspring were born, a hypoxia experiment was conducted every other day, 5 rounds each time, 10min hypoxia and 5min reoxygenation each round. This group was the normal hypoxia group; the other group of offspring was subjected to extreme hypoxia. From the 10th day after the offspring were born, the animals were placed in a transparent hypoxia device every day, and the animal status was continuously observed. When the animal started and lay prone, opened its mouth to breathe, the mouth, nose and limbs were cyanotic, the eyeballs darkened, and the whole body trembled, the hypoxia device was gently shaken. If the animal started, hypoxia continued until the animal still lay prone and breathed heavily after the hypoxia device was gently shaken, and the hypoxia was stopped immediately. The animal status needs to be closely monitored during the hypoxia process to avoid excessive hypoxia and death of the animal. This group is the extreme hypoxia group.

[0082] 2) Index detection

[0083] Since the first experiment found that the distance animals crawled forward and the number of times they fell were very different, the experimenters decided to replace this indicator in Table 1 with the indicator in Table 3, and add the measurement of the pulling force value on the 28th day after the birth of the pups. The specific test indicators are as follows:

[0084] (1) Pregnant mouse production indicators: number of days to delivery, whether there is stillbirth after delivery (survival rate), and number of babies per litter;

[0085] (2) Newborn mice (unweaned): age at eye opening, weight at birth, and skin color at birth. Newborn mice were weighed once a week until weaning.

[0086] (3) The following experiments were performed and scored on newborn mice at 14, 21, and 28 days after birth.

[0087] Table 3 Behavioral index scoring standard table (updated)

[0088]

[0089]

[0090] Model establishment judgment:

[0091] When pregnant mice give birth prematurely, their pups die after birth, less than 10 animals survive each litter, and their pups open their eyes later than 14 days old, it is judged that the mother has successfully suffered from hypoxia. 28 days after the pups are born, if the sum of the three behavioral scores is higher than 6 points, it is judged that the pups have successfully suffered from hypoxia. The higher the score, the more severe the brain damage.

[0092] 3) Experimental results

[0093] Pregnant rat No. 3 gave birth to 10 pups on the 18th day of pregnancy (3 days premature), the skin color of the pups was purple-red, 1 pup died, and the rest of the pups opened their eyes on the 16th day of birth, judging that the hypoxia of pregnant rat No. 3 was successful; one pup died in the extreme hypoxia group on the 12th day of extreme hypoxia, so the hypoxia experiment was changed from one day to one every other day. The behavioral indexes of the pups born by pregnant rat No. 3 were scored, and the results are shown in Table 4.

[0094] According to the data in Table 4, when the pups born to pregnant mouse No. 3 were 28 days old, the sum of the three behavioral scores of the normal hypoxia group did not reach 6 points, so the hypoxia of the normal hypoxia group was not successful; when the pups were 28 days old, the sum of the three behavioral scores of the extreme hypoxia group was 8 points, so the hypoxia of the extreme hypoxia group was judged to be successful.

[0095] Table 4 Behavioral index score table of the offspring born by pregnant mouse No. 3

[0096]

[0097]

[0098] Note: Compared with the normal hypoxia group, *P<0.05, **P<0.01, ***P<0.001;

[0099] According to the experimental results after the second optimization of conditions, the formal experimental modeling was carried out by using multiple indirect hypoxia of maternal mice and multiple extreme hypoxia of offspring to induce brain damage in neonates. The advantage of this model is that it is closer to the clinical process of brain injury in children, the operation is simple, and no surgery or injection of induction agents are used for intervention, which reduces the harm to experimental animals.

[0100] 3. Formal Experiment

[0101] 3.1 Experimental process

[0102] 1) Model construction

[0103] This experimental model consists of two stages. The first stage is multiple hypoxia (intermittent and staged continuous hypoxia) during pregnancy, which causes brain damage in fetal mice. The specific method is: 13 pregnant mice were divided into 3 normal animals and 10 model animals. The normal group of pregnant mice did not receive any treatment. The model group of pregnant mice began to undergo a hypoxia experiment every 1 day from the 10th day of pregnancy, and a hypoxia experiment was performed once a day from the 14th to the 18th day of pregnancy. No hypoxia experiment was performed after the 18th day of pregnancy. Five rounds of hypoxia were performed each time, each round of hypoxia lasted 10 minutes, and reoxygenation lasted 5 minutes.

[0104] The second stage is multiple intermittent hypoxia during the lactation period of the pups, which aggravates the degree of brain damage in the pups and delays the development of brain tissue in the pups. The specific method is as follows: the pups born by pregnant mice in the model group are subjected to an extreme hypoxia experiment every other day starting from the 10th day after birth (the extreme hypoxia method is the same as the pre-experimental extreme hypoxia method) until weaning.

[0105] 2) Index detection during modeling

[0106] The indicator detection and evaluation criteria are the same as the behavioral indicator scoring criteria determined in the second exploratory experiment in the preliminary experiment.

[0107] 3) Grouping

[0108] Since the preliminary experimental results showed that there was not much difference in the "slope test" and "abnormal posture" scores of the animals on the 28th day, the grouping of this experiment was based on the weight, hanging rod test score and grasping strength value of the pups on the 28th day after birth. The mice were divided into a normal group, a model group, a test drug group, a positive drug group and a combination group, with 8 animals in each group, half of which were male and half were female.

[0109] 4) Drug administration

[0110] The animals in the normal group and the model group were given normal saline with the same dose of the test drug;

[0111] The drug group was given Platycodon grandiflorum and Douchi decoction (provided by the client), which was taken orally by gavage, for a total of 14 doses (70g of crude drug / dose), and the drug dose for each dose was twice that of a five-year-old child. The dose for mice was 0.17g / 10g of crude drug based on the weight of a child of 18kg, and the administration volume was 0.1ml / 10g;

[0112] The positive drug group was given only injectable nerve growth factor, which was administered by hind limb intramuscular injection. According to the clinical dosage for children, one vial per day, each vial is about 18ug, and 2ml of sterile injection water is required to dissolve. Based on the weight of 18kg children, the dosage for mice is calculated to be 0.09ug / 10g, and the administration volume is 0.01ml / 10g;

[0113] The combination group was administered with the test drug and the positive drug, and the dosage, volume and method of administration were the same as when the two drugs were used alone.

[0114] 5) Preparation method of test drug

[0115] (1) Soaking the combined medicine provided in Example 1: Put all the Chinese medicines into a container and add 350 ml of water to soak for 15 minutes;

[0116] (2) Decoction: Place the container on the induction cooker and select the hot pot mode;

[0117] A. Fry over high heat (2200W) for 1 minute;

[0118] B. Change to medium heat (300W) and fry for 3 minutes;

[0119] C. Cover the lid and fry for 20 minutes on low heat (120W) - open the lid and fry for 20 minutes;

[0120] D. Filtration;

[0121] E. Transfer to a 50ml centrifuge tube and confirm the volume (about 20ml)

[0122] (3) Secondary decoction: Add 100 ml of water into the container, boil over medium heat (300 W) for 2 min, then turn to low heat (120 W) for 20 min;

[0123] (4) Filtration, same steps as above;

[0124] (5) Mix the two decoctions (about 40 ml), cool them down, and store them at 4°C.

[0125] 6) Dynamic detection indicators

[0126] Each group of mice was given medication according to the medication standards, and then the indicators of each group of mice were tested, specifically:

[0127] (1) The hanging test and tensile force value were measured 7 days (D36), 14 days (D43), 21 days (D50), and 28 days (D57) after administration. Since it is necessary to more clearly reflect the efficacy of the drug, the hanging test score was changed to record the hanging time (s).

[0128] (2) Behavioral video recording: On the day of the first administration (D29), 7 days after administration (D36), 14 days after administration (D43), 21 days after administration (D50), and 28 days after administration (D57), four mice were video recorded in one cage, each time for 15 min;

[0129] (3) Weight record: Once a week during the dosing period after birth, in accordance with the company's SOP.

[0130] 7) Draw materials

[0131] After 28 days of drug administration, all mice were killed and samples were collected, including the following steps:

[0132] (1) Eyeballs were removed and blood was collected. The serum was stored at -80°C (NSE or S-100 levels could be measured later if necessary). Each group had no less than 3 mice.

[0133] (2) routine organs were collected to calculate the organ index and then stored in paraformaldehyde at room temperature;

[0134] (3) Brain tissue was removed. Brain tissues of 3 animals were selected from each group. They were quickly frozen in liquid nitrogen and stored at -80°C (they can be sent for inspection later if needed); brain tissues of 4 animals were selected from each group for TTC staining. The TTC staining method is as follows: the brain tissue was weighed and frozen at -20°C for more than 15 minutes, and then taken out. Use a surgical blade to cut it into 6 slices along the coronal plane, put it into a culture dish containing 1% TTC solution (1g dissolved in 100ml cold PBS solution), and placed in a 37°C mold incubator for 20 minutes. The staining process needs to be protected from light. After the staining is completed, take it out for observation and take pictures.

[0135] 3.2 Experimental Results

[0136] According to the above test process, the experimental results are as follows:

[0137] 1) Modeling results

[0138] First, the production index comparison data of pregnant mice in the normal group and the model group were obtained, as shown in Table 5; the animals in the model group gave birth prematurely (average premature birth of 3 days), and the pups died after delivery (mortality rate was 17%), and the number of animals surviving each litter was less than 10, and the pups opened their eyes later than 14 days, which determined that the mother mice were successfully hypoxic.

[0139] Table 5 Comparison of production indicators between normal group and model group pregnant mice

[0140]

[0141] Note: Due to the large difference in the number of animals, no statistical analysis was performed.

[0142] The behavioral index scores of the offspring of the normal group pregnant mice and the model group pregnant mice were scored. The obtained index score table is shown in Table 6, and the line graph is shown in Figure 2 As shown, the results showed that the score of the modeling group was significantly higher than that of the normal group, and the sum of the three behavioral scores on the 28th day was 7.73 points, which was higher than 6 points, indicating that the hypoxia of the pups was successful.

[0143] Table 6 Behavioral index score table of the offspring born by pregnant mice in the normal group and the model group

[0144]

[0145] Note: Due to the large differences in the number of offspring produced by the animals, no statistical analysis was performed.

[0146] In summary, this model of brain injury caused by intrauterine hypoxia was established.

[0147] The normal group and the model group were subjected to tensile test, and the results are shown in Table 7 and Figure 3 As shown in Table 7 and Figure 3 The results showed that the tensile force values ​​in the model group were significantly lower than those in the normal group, indicating that the tensile force became significantly weaker when the animals suffered brain damage.

[0148] Table 7 Tensile strength test of normal group and model group

[0149]

[0150] Note: Due to the large differences in the number of offspring produced by the animals, no statistical analysis was performed.

[0151] The body weights of the mice in the normal group and the model group were recorded. Figure 4 As shown in Table 8, according to Table 4 and Figure 3 The results showed that the growth rate of animals in the model group was lower than that of animals in the normal group, indicating that when animals suffer brain damage, their growth rate slows down.

[0152] Table 8 Weight record of rats in normal group and model group (g)

[0153]

[0154] Note: Due to the large differences in the number of offspring produced by the animals, no statistical analysis was performed.

[0155] 2) Grouping results

[0156] This experiment was divided into three groups according to the weight, hanging rod test score and gripping strength value of the pups on the 28th day after birth. Each group had 8 animals, half of which were male and half were female. The higher the score, the more severe the brain damage of the animal, and the lower the gripping strength value, the more severe the brain damage of the animal. Since the animals in the normal group (pregnant mice and pups) had not undergone hypoxia experiments, the weight, score, and gripping strength of the animals in the normal group showed statistical differences (P<0.05) and extremely significant statistical differences (P<0.001) from those in the other groups; the baselines of the model group and the drug-treated groups were consistent, and no statistical differences were found, as shown in Table 9 for details.

[0157] Table 9 Animal grouping record

[0158]

[0159] Note: Compared with the normal group, *P<0.05, **P<0.01, ***P<0.001;

[0160] Compared with the model group, # P<0.05, ## P<0.01, ### P<0.001.

[0161] 3) Efficacy results

[0162] The body weights of the offspring in the model group and the normal group were recorded during the administration period. The results are shown in Table 10. Figure 5 As shown, the results showed that the body weight of the model group was lower than that of the normal group, and there was a significant statistical difference at 7 days (D36) of administration (P<0.01); compared with the model group, the body weight gain of each medication group was lower than that of the model group, which was more obvious in male animals, and statistical differences appeared after one week of administration (P<0.05).

[0163] Table 10 Weight record of animals in each group during the drug administration period

[0164]

[0165]

[0166] Note: Compared with the normal group, *P<0.05, **P<0.01, ***P<0.001;

[0167] Compared with the model group, # P<0.05, ## P<0.01, ### P<0.001.

[0168] The mice in each group were subjected to the hanging rod test and the tensile test during the administration period. The results of the hanging rod test are shown in Table 11 and Figure 6 As shown in Table 12 and Figure 7 shown.

[0169] According to Table 11 and Figure 6The results showed that compared with the normal group, the model group had significantly shorter hanging time than the normal group, and there were significant statistical differences (P<0.01) and extremely significant statistical differences (P<0.001) 7 days after administration (D36) and thereafter; compared with the model group, the hanging time of each medication group was significantly longer than that of the model group. The male animals in the combination group showed statistical differences (P<0.05) compared with the male animals in the model group at 7 days (D36) of drug administration, and extremely significant statistical differences (P<0.001) were found at 14 days (D43) of drug administration and thereafter. The female animals in the combination group also showed significant statistical differences (P<0.01) compared with the female animals in the model group at 14 days (D43) of drug administration, and extremely significant statistical differences (P<0.001) were found at 21 days (D50) of drug administration and thereafter. The efficacy of the test drug was similar to that of the positive drug. The male animals in the test drug group showed statistical differences (P<0.05) compared with the male animals in the model group at 14 days (D43) of drug administration, and extremely significant statistical differences (P<0.001) were found at 21 days (D50) of drug administration and thereafter. There were extremely significant statistical differences (P<0.001) on and after the administration. The female animals in the test drug group also showed statistical differences (P<0.05) compared with the female animals in the model group at 21 days (D50) of administration, and significant statistical differences (P<0.01) were found at 28 days (D57) of administration. There were significant statistical differences (P<0.01) between the male animals in the positive drug group and the male animals in the model group at 21 days (D50) of administration, and extremely significant statistical differences (P<0.001) were found at 28 days (D57) of administration. There were also statistical differences (P<0.05) between the female animals in the positive drug group and the female animals in the model group at 21 days (D50) of administration and after the administration.

[0170] Table 11 Record of the duration of hanging time of animals in each group during the drug administration period (s)

[0171]

[0172]

[0173] Note: Compared with the normal group, *P<0.05, **P<0.01, ***P<0.001;

[0174] Compared with the model group, # P<0.05, ## P<0.01, ### P<0.001.

[0175] According to Table 12 and Figure 7The results showed that the tensile force of the model group was significantly lower than that of the normal group, and there were extremely significant statistical differences (P<0.001) and significant statistical differences (P<0.01) 7 days after administration (D36) and thereafter; the tensile force of each drug-administered group was significantly higher than that of the model group. The male animals in the combination group showed significant statistical differences compared with the male animals in the model group at 7 days (D36) and thereafter, and the female animals in the combination group also showed statistical differences compared with the female animals in the model group at 14 days (D43) and 28 days (D57) of administration (P<0.05); the male animals in the test drug group showed significant statistical differences compared with the male animals in the model group at 21 days (D50) of administration (P<0.01), and at 28 days (D57) of administration (P<0.05), and the female animals in the test drug group also showed statistical differences compared with the female animals in the model group at 28 days (D57) of administration (P<0.05); the male animals in the positive drug group showed significant statistical differences compared with the male animals in the model group at 28 days (D57) of administration (P<0.01).

[0176] Table 12 Record of pulling force values ​​of animals in each group during the drug administration period (kg)

[0177]

[0178]

[0179] Note: Compared with the normal group, *P<0.05, **P<0.01, ***P<0.001;

[0180] Compared with the model group, # P<0.05, ## P<0.01, ### P<0.001.

[0181] After 28 days of administration, all mice were killed and the organ indexes were tested. The results are shown in Table 12 and Figure 8 As shown in Table 12 and Figure 8 The results showed that the liver index of the model group was higher than that of the normal group, the liver index of male animals showed statistical difference (P<0.05), and the liver index of female animals showed significant statistical difference (P<0.01); compared with the model group, the liver index of each drug-treated group was lower than that of the model group, among which the liver index of female animals in the test drug group showed extremely significant statistical difference compared with the model group (P<0.001), and the liver index of female animals in the positive drug group also showed statistical difference compared with the model group (P<0.05).

[0182] Table 13 Record of organ index of each group of animals (%)

[0183]

[0184] Note: Compared with the normal group, *P<0.05, **P<0.01, ***P<0.001;

[0185] Compared with the model group, # P<0.05, ## P<0.01, ### P<0.001.

[0186] The animals in the model group were exposed to hypoxia in the mothers and offspring. TTC staining showed that the ischemic part of the brain in the model group was widely distributed. Compared with the model group, the distribution of ischemic sites in the brain of the other drug-treated groups was reduced, and the ischemic area was also improved. The effect of the combined group was the most obvious. The results are shown in detail. Fig. 9 shown.

[0187] Based on the above experimental data, it can be known that the use of the test drug (the composition provided in Example 1) has a significant effect on the treatment of brain injury, and the combination of drugs (the combination drug provided in Example 4) uses growth factors to replace the toxic components recorded in Treatise on Febrile Diseases, and the combination provided in this example significantly improves the effect of treating brain injury.

[0188] By adopting the above technical solution disclosed in the present invention, the following beneficial effects are obtained:

[0189] The composition for assisting the treatment of cerebral palsy provided in this embodiment is created based on Guati Powder and Sanwu Bai Powder in Treatise on Febrile Diseases, and the toxic drugs in the above two prescriptions are removed, and only light fermented black beans, red beans, platycodon, fritillaria, rhubarb, scutellaria and almonds are retained. As an oral decoction, because the toxic taste of the original prescription is removed, the safety is extremely high. The Chinese medicine composition can achieve the same efficacy as nerve growth factor when used alone, significantly reducing the cost of treatment. When used in combination with nerve growth factor, the efficacy of treating cerebral palsy as a new drug combination can be significantly improved.

[0190] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be considered as the scope of protection of the present invention.

Claims

1. A Chinese medicinal composition for treating cerebral palsy, characterized in that: The invention is prepared from the following raw materials in parts by weight: 2-3 parts of French pinellia, 1-3 parts of cooked rhubarb, 4-6 parts of adzuki beans, 4-6 parts of light fermented black beans, 2-4 parts of platycodon, 5-7 parts of thunbergii, 3-5 parts of stir-fried bitter almonds, 2-4 parts of ginger magnolia bark and 3-5 parts of scutellaria baicalensis.

2. The Chinese medicinal composition for treating cerebral palsy according to claim 1, characterized in that: The drug is prepared from the following raw materials in parts by weight: 3 parts of French pinellia, 2 parts of cooked rhubarb, 5 parts of red bean, 6 parts of light fermented black beans, 3 parts of platycodon, 6 parts of thunbergii, 5 parts of stir-fried bitter almonds, 2 parts of ginger magnolia bark and 4 parts of scutellaria baicalensis.

3. The Chinese medicinal composition for treating cerebral palsy according to claim 1 or 2, characterized in that: The preparation form of the traditional Chinese medicine composition is one of tablets, dispersants, soft capsules, granules, pills, gels and oral liquid preparations.

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