Longgui root orifice-opening pill and preparation method thereof

Abstract

The invention relates to the field of traditional Chinese medicine compositions, in particular to a dragon, angelica sinensis and root orifice-opening pill and a preparation method thereof, and the dragon, angelica sinensis and root orifice-opening pill is prepared from the following raw materials in parts by weight: 210 parts of astragalus membranaceus, 140 parts of angelica sinensis, 140 parts of kudzu vine root, 105 parts of ligusticum wallichii, 70 parts of earthworm, 70 parts of salvia miltiorrhiza, 70 parts of red paeony root, 70 parts of safflower, 105 parts of motherwort and corn starch as an auxiliary material. The traditional Chinese medicine preparation disclosed by the invention has remarkable innovation points in compatibility and a preparation process, and the innovation points act together, so that the preparation has unique advantages and a good application prospect in the aspect of treating related diseases of qi deficiency and blood stasis syndromes.

Description

Technical Field

[0001] The present invention relates to the field of Chinese medicine preparations, and in particular to a Chinese medicine preparation for treating diseases related to qi deficiency and blood stasis syndrome, in particular ischemic cerebrovascular diseases, and a preparation method and application thereof. Background Art

[0002] Ischemic cerebrovascular disease seriously endangers human health, and existing therapeutic drugs have limitations. Traditional Chinese medicine has unique advantages in improving symptoms and improving the quality of life of patients. Chinese herbal compound preparations play a synergistic role through reasonable compatibility, providing new options for the treatment of this disease. There are many traditional Chinese medicine prescriptions for the treatment of qi deficiency and blood stasis, but some prescriptions have the problem of relatively simple drug composition or lack of pertinence. Some prescriptions only focus on promoting blood circulation and removing blood stasis, but ignore the correction of qi deficiency, the fundamental cause of the disease, resulting in poor treatment effect or easy recurrence of the disease. For example, some Chinese herbal compound prescriptions for promoting blood circulation and removing blood stasis have a certain effect on improving blood rheology indicators, but they do not significantly improve the symptoms of fatigue and shortness of breath caused by qi deficiency in patients, and their overall ability to regulate body functions is limited.

[0003] The synergistic effect between drugs in existing combinations has not been fully utilized. Although the drug combinations in some prescriptions have certain theoretical basis, in actual application, due to the influence of factors such as drug dosage and processing methods, the synergistic effect between the drugs has not reached the optimal state. For example, in some prescriptions, the ratio of astragalus and other blood-activating drugs is unreasonable, so that the qi-tonifying effect of astragalus cannot effectively promote blood circulation, thus affecting the overall therapeutic effect.

[0004] In terms of raw material processing, there is a lack of unified and strict standards. During the processing of Chinese medicinal materials from different origins and batches, due to differences in operating methods, the content of active ingredients may be unstable or the efficacy may change. For example, during the processing of Astragalus, different wetting time and drying conditions will affect the content and activity of the active ingredients in Astragalus, and thus affect the quality and efficacy of the preparation. The cleaning and impurity removal methods of raw materials are not scientific enough. Some traditional cleaning methods may not be able to completely remove harmful substances such as pesticide residues and heavy metals on the surface of Chinese medicinal materials, posing a potential threat to the safety of drugs. At the same time, incomplete impurity removal will also affect the purity and quality of the drugs. In the pulverization process, most of them only perform simple coarse pulverization, and the drug particles are large, resulting in slow dissolution of the active ingredients and low bioavailability. This requires patients to take larger doses of drugs to achieve the desired effect, which increases the burden on patients and may also increase the risk of adverse drug reactions. The mixing process lacks precise control, and it is easy to cause uneven drug mixing. In the preparation, uneven distribution of drug ingredients may lead to inconsistent efficacy of each dose of drug, affecting the accuracy and stability of treatment. For example, in the preparation of pills, if the drugs are not mixed evenly, the content of active ingredients ingested by patients when taking different pills may vary greatly, affecting the evaluation of the therapeutic effect and the treatment process of the disease. In the process of preparation molding, pills, tablets and other dosage forms made by traditional processes have great differences in appearance, hardness, disintegration time and other aspects. Unsightly appearance may affect patients' medication compliance; inappropriate hardness may cause the drug to break or deform during storage and transportation, affecting the stability of the drug; too long disintegration time will affect the release rate of the drug in the body and delay the onset of the drug. The packaging process is simple and lacks good moisture-proof, light-proof and other protective measures. Chinese medicine preparations are easily affected by environmental factors such as humidity and light during storage, resulting in degradation or deterioration of active ingredients. In addition, improper selection of packaging materials may also introduce external impurities, contaminate drugs, and reduce the quality and safety of drugs.

[0005] In summary, the existing Chinese medicine preparations for treating diseases related to qi deficiency and blood stasis syndrome have many defects in compatibility and preparation process, and there is an urgent need for a Chinese medicine preparation with reasonable drug compatibility and scientific preparation process to improve the therapeutic effect and ensure the quality and safety of the medicine. The Chinese medicine preparation of the present invention is developed to address these problems and is intended to provide more effective therapeutic drugs for patients with qi deficiency and blood stasis syndrome. Summary of the invention

[0006] The invention provides a Longguigen Tongqiao pill, which is prepared from the following raw materials in parts by weight: 210 parts of astragalus, 140 parts of angelica, 140 parts of kudzu root, 105 parts of chuanxiong, 70 parts of earthworms, 70 parts of salvia miltiorrhiza, 70 parts of red peony root, 70 parts of safflower and 105 parts of motherwort, and the auxiliary material is corn starch.

[0007] The Chinese medicine preparation is a pill, with the specification of each bag being equivalent to 9.2g of medicinal slices. The dosage is oral, 1 bag at a time, twice a day, or as prescribed by a doctor. It is used to treat dizziness, hemiplegia, limb apathy, tongue stiffness and slurred speech, drooling at the corners of the mouth, frequent urination, enuresis and incontinence, pale tongue with thin white fur and the like caused by qi deficiency and blood stasis syndrome, or ischemic cerebrovascular disease with the above symptoms.

[0008] The present invention also provides a method for preparing the Longguigen Tongqiao Pills Chinese medicine preparation, comprising the following steps:

[0009] Raw material pretreatment: accurately weigh each raw material according to the formula, each raw material is a Chinese herbal medicine slice that meets the national drug standards, and each raw material is processed and processed, and the specific methods are as follows: Astragalus: remove impurities, separate by size, wash, moisten, cut into thick slices, and dry; Angelica: remove impurities, wash, moisten, cut into thin slices, dry in the sun or dry at low temperature; Pueraria: remove impurities, wash, moisten, cut into thick slices, and dry in the sun; Chuanxiong: remove impurities, separate by size, wash, moisten, cut into thick slices, and dry; Pheretima: remove impurities, wash, cut into sections, and dry; Salvia: remove impurities and residual stems, wash, moisten, cut into thick slices, and dry; Red Peony: remove impurities, separate by size, wash, moisten, cut into thick slices, and dry; Safflower: remove impurities; Motherwort (dry): remove impurities, quickly wash, slightly moisten, cut into sections, and dry;

[0010] Crushing: Spread the processed raw pieces of medicine on a stainless steel plate with a thickness of 1 cm, put them into an oven, and dry them at 70°C for 5 hours, so that the microbial limit of the raw pieces of medicine meets the standard and is suitable for crushing. The dried raw pieces of medicine are mixed according to the prescription ratio and then crushed. 100% of the powder is sieved through an 80-mesh sieve, and 95% is sieved through a 100-mesh sieve to obtain a mixed powder;

[0011] Preparation molding: Take the mixed powder, add 15% starch slurry solution (take an appropriate amount of dry starch and make it into a paste with boiling water) as a binder, the weight ratio of powder to starch slurry is 100:60, cover the mixer cover and stir for 10 minutes. After mixing evenly, it feels moderately soft and hard, sticky when held, and slightly dispersed when loosened. Make a medicine ball, add the medicine ball to the automatic pill making machine, adjust the equipment knife and the outlet to make the particle size of 4mm, make pills, and get pills. Spread the pills on the medicine receiving tray with a thickness of no more than 2cm. First cool them in a clean area to harden the surface of the pills, then spread them out on different trays, use hot air circulation drying method, dry them at 80℃ for 5 hours, load the dried pills into a water chestnut-type sugar coating machine, and add Add appropriate amount of purified water, turn on the hot air and cold air of the sugar coating machine to gradually dry the moisture on the surface of the water pills, and polish them until the surface of the pills is smooth and bright. Use the method of manual pill selection to pick out connected pills and residual pills to ensure the appearance quality of the water pills, and then carry out inner packaging. The inner packaging is sealed using a water pill packaging machine. The inner packaging material is a medicinal composite film. Each bag is packaged with 10g. The difference in filling volume is between ±4% of 10g (9.6g~10.4g) according to the requirements of the pharmacopoeia. Each bag is coded with "production date, preparation batch number, and expiration date" at the corresponding position. The outer packaging is to put the medicine bags with plastic-sealed inner packaging into the outer packaging box with "production date, preparation batch number, and expiration date" according to the packaging specifications of the preparation to obtain the finished product.

[0012] The Chinese medicine preparation is used in preparing medicines for treating diseases related to Qi deficiency and blood stasis syndrome, wherein the diseases related to Qi deficiency and blood stasis syndrome include ischemic cerebrovascular disease.

[0013] The present invention also provides a drug combination for treating diseases related to qi deficiency and blood stasis syndrome, comprising the traditional Chinese medicine and a pharmaceutically acceptable auxiliary material or carrier, and the dosage form of the drug combination is a pill.

[0014] The drug combination also includes other drugs for treating ischemic cerebrovascular diseases, and the traditional Chinese medicine preparation has a synergistic effect when used in combination with other drugs.

[0015] Beneficial effects:

[0016] It is composed of multiple Chinese medicines and treats multiple targets of Qi deficiency and blood stasis syndrome. The experiment showed that the complete formula was significantly better than the drug-deficient group in improving the blood rheology indexes of model rats, reducing brain tissue pathological damage and regulating serum NO and ET levels, reflecting the synergistic effect of each drug. Astragalus is the main drug to replenish qi and promote blood circulation. Angelica, Chuanxiong, earthworm and Salvia miltiorrhiza assist the main drug to promote blood circulation and dredge collaterals. Pueraria root, red peony root, safflower and motherwort assist the main drug and ministers, respectively playing the role of promoting blood circulation and activating collaterals, clearing heat and cooling blood. The whole formula makes the drug properties reach the diseased area directly, and play the role of replenishing qi and activating blood circulation, removing blood stasis and dredge collaterals. Astragalus, Angelica and Chuanxiong synergistically reduce the whole blood viscosity, and the effect is weakened when one of them is missing; earthworm and Salvia miltiorrhiza regulate plasma viscosity, and the effect is not good when they are missing; Pueraria root and red peony root improve red blood cell aggregation, and the reduction is not obvious when they are missing; safflower and motherwort protect brain tissue, and the pathological changes are aggravated when they are missing. Each raw material is processed specifically, such as astragalus, which is processed according to its characteristics, and impurities are removed to ensure efficacy. Pretreatment specifications ensure the consistency of raw material quality. Drying at 70℃ for 5 hours meets the standard and is conducive to crushing. Screening with a specific mesh number makes the powder particle size uniform and the specific surface area large, which is conducive to absorption and ensures uniform and stable preparations. 15% starch slurry and a specific ratio are used to make adhesive pills, and the equipment is adjusted to make 4mm pills. Multi-step drying and polishing ensure the appearance quality, manual pill selection and standardized packaging ensure quality traceability and standardized production, and guarantee the quality and safety of preparations. DETAILED DESCRIPTION

[0017] Example 1

[0018] 1. Raw material preparation and pretreatment

[0019] 1. According to the formula, accurately weigh 210g of Astragalus, 140g of Angelica, 140g of Pueraria, 105g of Chuanxiong, 70g of Pheretima, 70g of Salvia miltiorrhiza, 70g of Red Peony Root, 70g of Carthamus tinctorius, and 105g of Leonurus japonicus. All raw materials are Chinese herbal medicines that meet national drug standards.

[0020] 2. Astragalus: remove impurities, separate by size, wash, soak, cut into thick slices, and dry. Angelica: remove impurities, wash, soak, cut into thin slices, and dry in the sun or at low temperature. Pueraria: remove impurities, wash, soak, cut into thick slices, and dry in the sun. Chuanxiong: remove impurities, separate by size, wash, soak, cut into thick slices, and dry. Pheretima:

[0021] Remove impurities, wash, cut into sections, and dry. Salvia miltiorrhiza: remove impurities and residual stems, wash, moisten thoroughly, cut into thick slices, and dry. Red peony root: remove impurities, separate into large and small, wash, moisten thoroughly, cut into thick slices, and dry. Safflower: remove impurities. Motherwort (dry): remove impurities, wash quickly, moisten slightly, cut into sections, and dry.

[0022] 2. Crushing

[0023] 1. Spread the processed raw pieces of medicine flat on a stainless steel plate with a thickness of 1 cm, put them into an oven, and dry them at 70°C for 5 hours to ensure that the microbial limit of the raw pieces of medicine meets the standard and is suitable for crushing.

[0024] 2. The dried raw medicinal pieces are mixed according to the prescription ratio and then crushed, 100% of the powder is passed through an 80-mesh sieve, and 95% is passed through a 100-mesh sieve to obtain a mixed powder.

[0025] 3. Preparation molding

[0026] 1. Take the mixed powder and add 15% starch slurry solution (take an appropriate amount of dry starch and make it into a paste with boiling water)

[0027] As an adhesive, the weight ratio of drug powder to starch slurry is 100:60. Cover the mixer lid and stir for 10 minutes. After mixing evenly, it feels moderately soft and hard, sticky when held, and slightly loose when loosened, and the drug ball is made.

[0028] 2. Add the medicine lump into the automatic pill making machine, adjust the equipment tool and the outlet to make the particle size 4mm, and make pills to obtain pills.

[0029] 3. Spread the pills flat on the medicine receiving tray with a thickness not exceeding 2 cm. Let them cool in a clean area first to harden the surface of the pills. Then spread them out on the trays and dry them at 80°C for 5 hours using hot air circulation drying method.

[0030] 4. Put the dried pills into the water chestnut-type sugar coating machine, add appropriate amount of purified water, turn on the hot air and cold air of the sugar coating machine to gradually dry the moisture on the surface of the water pills, and polish them until the surface of the pills is smooth and bright.

[0031] 5. The method of manual pill selection is adopted to pick out connected pills and residual pills to ensure the appearance quality of water pills, and then the inner packaging is carried out. The inner packaging is sealed using a water pill packaging machine. The inner packaging material is a medicinal composite film. Each bag is packed with 10g. The difference in filling volume is within ±4% of 10g (9.6g-10.4g) according to the requirements of the pharmacopoeia. Each bag is coded at the corresponding position.

[0032] “Production date, preparation batch number, expiration date”.

[0033] 6. Outer packaging: Put the inner plastic-sealed medicine bags into the outer packaging boxes marked with "production date, preparation batch number, and expiration date" according to the preparation packaging specifications and quantity to obtain the finished Chinese medicine preparation.

[0034] Example 2

[0035] 1. Raw material preparation and pretreatment (lack of Astragalus)

[0036] 1. Weigh 140g of Chinese angelica, 140g of kudzu root, 105g of chuanxiong, 70g of earthworm, 70g of salvia miltiorrhiza, 70g of red peony root, 70g of safflower, and 105g of motherwort, all of which are Chinese herbal medicine pieces that meet the standards. Prepare and process each raw material according to the method in Example 1.

[0037] 2. Crushing and preparation molding (same steps as in Example 1)

[0038] 1. Grinding: Dry the processed raw medicinal pieces under the same conditions as above, mix and grind them according to the proportion, and sieve to obtain the mixed medicinal powder.

[0039] 2. Formulation: The same process as in Example 1 is adopted, and the same proportion of starch slurry solution is added to form medicine pellets, and operations such as pelleting, drying, polishing, pellet selection, and packaging are performed to obtain the finished product.

[0040] Example 3

[0041] 1. Raw material preparation and pretreatment (without angelica)

[0042] 1. Weigh 210 g of Astragalus, 140 g of Pueraria, 105 g of Chuanxiong, 70 g of Pheretima, 70 g of Salvia miltiorrhiza, 70 g of Red Peony Root, 70 g of Carthamus tinctorius, and 105 g of Leonurus japonicus, and prepare and process them in the same manner as in Example 1.

[0043] 2. Crushing and preparation molding (same steps as in Example 1)

[0044] 1. Carry out drying, crushing and formulation molding operations according to the conditions in Example 1 to finally obtain a finished product.

[0045] Example 4

[0046] 1. Raw material preparation and pretreatment (lack of Pueraria root)

[0047] 1. Prepare 210g of Astragalus, 140g of Angelica, 105g of Chuanxiong, 70g of Pheretima, 70g of Salvia miltiorrhiza, 70g of Red Peony Root, 70g of Carthamus tinctorius, and 105g of Leonurus japonicus, and the processing process is the same as Example 1.

[0048] 2. Crushing and preparation molding (same steps as in Example 1)

[0049] 1. Repeat the drying, crushing and formulation molding process of Example 1 to obtain a finished product.

[0050] Example 5

[0051] 1. Raw material preparation and pretreatment (lack of Chuanxiong)

[0052] 1. Weigh 210g of Astragalus, 140g of Angelica, 140g of Pueraria, 70g of Pheretima, 70g of Salvia, 70g of Red Peony, 70g of Carthamus, and 105g of Leonurus, and process according to the standard.

[0053] 2. Crushing and preparation molding (same steps as in Example 1)

[0054] 1. Carry out subsequent operations according to the method of Example 1 to produce a finished product.

[0055] Example 6

[0056] 1. Raw material preparation and pretreatment (lack of earthworms)

[0057] 1. Take 210g of Astragalus, 140g of Angelica, 140g of Pueraria, 105g of Chuanxiong, 70g of Salvia miltiorrhiza, 70g of Red Peony Root, 70g of Carthamus tinctorius, and 105g of Leonurus japonicus, and pre-treat them as in Example 1.

[0058] 2. Crushing and preparation molding (same steps as in Example 1)

[0059] 1. According to the process steps of Example 1, drying, crushing, pilling, drying, polishing, packaging, etc. are completed to obtain a finished product.

[0060] Example 7

[0061] 1. Raw material preparation and pretreatment (lack of Salvia miltiorrhiza)

[0062] 1. Prepare 210g of Astragalus, 140g of Angelica, 140g of Pueraria, 105g of Chuanxiong, 70g of Pheretima, 70g of Red Peony Root, 70g of Carthamus, and 105g of Leonurus japonicus, and process them according to the method of Example 1.

[0063] 2. Crushing and preparation molding (same steps as in Example 1)

[0064] 1. Operate according to the conditions of Example 1 to obtain a finished product.

[0065] Example 8

[0066] 1. Raw material preparation and pretreatment (lack of red peony root)

[0067] 1. Weigh 210 g of Astragalus, 140 g of Angelica, 140 g of Pueraria, 105 g of Chuanxiong, 70 g of Pheretima, 70 g of Salvia, 70 g of Carthamus, and 105 g of Leonurus, and perform pretreatment as in Example 1.

[0068] 2. Crushing and preparation molding (same steps as in Example 1)

[0069] 1. Follow the steps of Example 1 to make the finished product.

[0070] Example 9

[0071] 1. Raw material preparation and pretreatment (lack of safflower)

[0072] 1. Prepare 210g of Astragalus, 140g of Angelica, 140g of Pueraria, 105g of Chuanxiong, 70g of Pheretima, 70g of Salvia miltiorrhiza, 70g of Red Peony Root, and 105g of Leonurus japonicus, and process them as in Example 1.

[0073] 2. Crushing and preparation molding (same steps as in Example 1)

[0074] 1. According to the process of Example 1, the finished product is prepared.

[0075] Example 10

[0076] 1. Raw material preparation and pretreatment (lack of motherwort)

[0077] 1. Take 210g of Astragalus, 140g of Angelica, 140g of Pueraria, 105g of Chuanxiong, 70g of Pheretima, 70g of Salvia miltiorrhiza, 70g of Red Peony Root, and 70g of Carthamus tinctorius, and process the raw materials according to the method of Example 1.

[0078] 2. Crushing and preparation molding (same steps as in Example 1)

[0079] 1. According to the process of Example 1, a finished product is made.

[0080] (I) Effects on blood rheology indices in rats with qi deficiency and blood stasis model

[0081] 1. Animal model establishment and grouping and drug administration

[0082] 1. Select clean male SD rats, adopt subcutaneous injection of epinephrine and ice water stimulation method to establish Qi deficiency and blood stasis model. The rats with successful modeling were randomly divided into 11 groups, 10 in each group, respectively, model control group, positive control group (given commercially available Chinese patent medicine for the treatment of Qi deficiency and blood stasis, administered according to the dosage of the instructions), and Example 1-10 groups. A normal control group (no modeling, normal feeding) was set up separately. Except that the normal control group and the model control group were given equal volumes of normal saline, the remaining groups were gavaged according to the corresponding drugs and dosages, once a day, and administered continuously for 4 weeks.

[0083] 2. Blood rheology index detection and result analysis

[0084] 1. Whole blood viscosity measurement

[0085]

[0086]

[0087] 2.

[0089] Note: Compared with the normal control group, **P<0.01; compared with the model control group, *P<0.05.

[0090] The results showed that the whole blood viscosity of the rats in the model control group was significantly higher than that of the normal control group at all shear rates (P<0.01). The whole blood viscosity of the rats in the Example 1 group was significantly lower than that in the model control group (P<0.05), and was close to the level of the normal control group at a high shear rate (200 / s); although the whole blood viscosity of the Example 2-10 groups was reduced to a certain extent, it was higher than that of the Example 1 group, among which the groups lacking Astragalus (Example 2), lacking Angelica (Example 3) and lacking Chuanxiong (Example 5) had a smaller reduction, and there was no statistically significant difference compared with the model control group (P>0.05). This shows that Astragalus, Angelica and Chuanxiong in the complete formula of the present invention play an important role in reducing whole blood viscosity, which may be related to their Qi-invigorating and blood-activating effects.

[0091]

[0092] Note: Compared with the normal control group, **P<0.01; compared with the model control group, *P<0.05.

[0093] The plasma viscosity of rats in the model control group increased significantly (P<0.01). The plasma viscosity of Example 1 group was significantly lower than that of the model control group (P<0.05). Among the Example 2-10 groups, the plasma viscosity of the group lacking earthworm (Example 6) and the group lacking salvia miltiorrhiza (Example 7) did not decrease significantly, and there was no statistically significant difference compared with the model control group (P>0.05). The other groups decreased to a certain extent but were still higher than the Example 1 group. This shows that earthworm and salvia miltiorrhiza are of great significance in regulating plasma viscosity, which may be related to their blood circulation and blood stasis effects.

[0094]

[0095] Note: Compared with the normal control group, **P<0.01; compared with the model control group, *P<0.05.

[0096] The red blood cell aggregation index of the model group increased (P<0.01). The red blood cell aggregation index of the Example 1 group was significantly lower than that of the model control group (P<0.05). In the Example 2-10 groups, the red blood cell aggregation index of the Pueraria root deficiency (Example 4) and the red peony root deficiency (Example 8) groups decreased slightly, and there was no statistically significant difference compared with the model control group (P>0.05), indicating that Pueraria root and red peony root play an important role in improving the state of red blood cell aggregation, which may be related to their effect of promoting blood circulation and activating collaterals.

[0097] (II) Effects on brain tissue pathology in rats with Qi deficiency and blood stasis model

[0098] 1. Sample preparation and observation methods

[0099] 1. After 4 weeks of administration, the rats were killed, and the brain tissues were removed, fixed, dehydrated, embedded, sliced, and stained with HE. The pathological changes of brain tissues were observed under an optical microscope.

[0100] 2. Analysis of pathological results (semi-quantitative scoring)

[0101]

[0102] 3.

[0104] Note: The scoring standard is 0-4 points, 0 points for no pathological changes, 4 points for the most severe pathological changes; compared with the normal control group,

[0105] **P<0.01; compared with the model control group, *P<0.05.

[0106] The neuronal structure of the rat brain tissue in the normal control group is intact, the cell morphology is normal, the nucleolus is clear, and there is no edema and inflammatory cell infiltration in the interstitium. The rat brain tissue in the model control group shows obvious pathological changes, neuronal cell degeneration, necrosis, nuclear condensation, deep staining, interstitial edema, and more inflammatory cell infiltration. The pathological damage of the rat brain tissue in the embodiment 1 group is significantly alleviated, the neuronal cell morphology is basically normal, and interstitial edema and inflammatory cell infiltration are significantly reduced. In the embodiment 2-10 group, the brain tissue pathological changes of the group lacking safflower (embodiment 9) and lacking motherwort (implementation. Example 10) are more serious than those of the embodiment 1 group, and some neuronal cell degeneration can still be seen, and the degree of interstitial edema and inflammatory cell infiltration is alleviated compared with the model control group but not as obvious as the embodiment 1 group; the pathological changes of other drug-deficient groups are between the embodiment 1 group and the group lacking safflower and motherwort, indicating that safflower and motherwort have a certain effect in protecting brain tissue and reducing pathological damage, which may be related to its blood circulation and blood stasis, diuresis and swelling-removing effects.

[0107] The Chinese medicine preparation of the present invention is composed of multiple Chinese medicines such as Radix Astragali, Radix Angelicae Sinensis, Radix Puerariae, Rhizoma Chuanxiong, Pheretima, Radix Salviae Miltiorrhizae, Radix Paeoniae Rubra, Flos Carthami, Herba Leonuri, and is directed to diseases related to qi deficiency and blood stasis syndrome, especially ischemic cerebrovascular disease, and exerts therapeutic effects from multiple targets and multiple approaches. Through the coordination of multiple effects such as invigorating qi, promoting blood circulation, unblocking collaterals, and removing blood stasis, the running state of qi and blood of the patient is improved comprehensively, and the body function is regulated. Compared with a single drug or a simple combination, the formula has significant advantages in therapeutic effect. In the experiment on rats with qi deficiency and blood stasis model, the complete formula group (embodiment 1) shows an effect that is significantly better than the drug-deficient group (embodiments 2-10) in terms of improvement of blood rheology indexes, alleviation of brain tissue pathological damage, and regulation of nitric oxide (NO) and endothelin (ET) levels in serum, which fully reflects the synergistic effect between each drug.

[0108] The main drug, the minister drug, the adjuvant drug and the assistant drug are reasonably matched. The main drug, Astragalus membranaceus, is the main drug in the prescription. It tastes sweet, is slightly warm in nature, and enters the spleen and lung meridians. It has the effects of replenishing qi and raising yang, consolidating the exterior and stopping sweating, promoting diuresis and reducing swelling, promoting fluid and nourishing blood, relieving stagnation and relieving arthritis, expelling toxins and draining pus, and healing sores and promoting tissue regeneration. In the syndrome of qi deficiency and blood stasis, Astragalus membranaceus can greatly replenish the vital energy. When qi is strong, blood can flow, providing power to promote blood circulation, fundamentally improving the state of qi deficiency, and playing a key therapeutic role against the main cause of the disease. Angelica sinensis, Chuanxiong, earthworms, and Salvia miltiorrhiza are the minister drugs. Angelica sinensis nourishes blood and activates blood circulation, regulates menstruation and relieves pain, moistens the intestines and promotes bowel movements. When used with Astragalus, it can replenish both qi and blood, making qi sufficient and blood thriving, and enhancing the power of blood circulation. Chuanxiong promotes blood circulation and qi, dispels wind and relieves pain, ascends to the head and descends to the sea of ​​blood. It is a qi medicine in the blood, which can help Angelica sinensis, Astragalus and other medicines to better promote the circulation of qi and blood and improve brain blood circulation. Earthworm is cold in nature and salty in taste. It has the effects of clearing away heat and calming the nerves, unblocking the meridians, relieving asthma, and diuresis. It can unblock the meridians and activate the meridians, especially good at unblocking the brain veins and improving the state of cerebral ischemia and hypoxia. Salvia miltiorrhiza can promote blood circulation and remove blood stasis, relieve menstruation and pain, clear the heart and relieve vexation, cool blood and eliminate carbuncle. It can strengthen the function of promoting blood circulation and removing blood stasis, and can clear the heart and relieve vexation. It has a relieving effect on symptoms such as vexation caused by blood stasis. It can assist the main medicine with other ministerial medicines to enhance the therapeutic effect. Pueraria root, red peony root, safflower, and motherwort are adjuvants. Pueraria root can relieve muscle and reduce fever, promote fluid production and quench thirst, clear rash, promote yang and stop diarrhea, promote blood circulation and activate collaterals, and guide drugs upward, which helps to improve brain symptoms. At the same time, it can promote fluid production and quench thirst, and has a regulating effect on insufficient body fluids that may be caused by blood stasis; red peony root can clear heat and cool blood, disperse blood stasis and relieve pain, which can not only help promote blood circulation and remove blood stasis, but also clear heat and cool blood, and prevent blood stasis from turning into heat after a long time; safflower can promote blood circulation and promote menstruation, disperse blood stasis and relieve pain, and its blood circulation and blood stasis-removing power is relatively strong, which can enhance the blood circulation effect of the whole prescription; motherwort can promote blood circulation and regulate menstruation, promote diuresis and reduce swelling, clear heat and detoxify, and promote diuresis and reduce swelling while promoting blood circulation, which helps to improve symptoms such as edema caused by blood stasis, and can clear heat and detoxify, prevent blood stasis from turning into heat and toxicity after a long time, and assist the monarch and minister drugs in treating diseases. The whole prescription is rationally matched and the drugs interact with each other, so that the medicinal properties reach the diseased area directly, and play the effects of invigorating qi, promoting blood circulation, removing blood stasis and unblocking collaterals, and is used to treat diseases related to qi deficiency and blood stasis syndrome.

[0109] In regulating blood rheology, drugs such as Astragalus, Angelica, and Chuanxiong work synergistically, and jointly reduce whole blood viscosity from the perspectives of invigorating qi and promoting blood circulation, and improve the hypercoagulable state of blood. Among them, Astragalus replenishes qi to help blood circulation, and Angelica and Chuanxiong directly promote blood circulation and remove blood stasis, which are indispensable. The effect of reducing whole blood viscosity in the drug-deficient group (such as Example 2 lacks Astragalus, Example 3 lacks Angelica, and Example 5 lacks Chuanxiong) is significantly weakened. Pheretima and Salvia miltiorrhiza are of great significance in regulating plasma viscosity. The two cooperate with each other to enhance the regulatory effect on plasma components. The plasma viscosity of the drug-deficient group (Example 6 lacks Pheretima, Example 7 lacks Salvia miltiorrhiza) is not improved well. Pueraria and red peony root play an important role in improving the aggregation state of red blood cells. They regulate the surface charge of red blood cells, etc., reduce red blood cell aggregation, and the red blood cell aggregation index of the drug-deficient group (Example 4 lacks Pueraria, Example 8 lacks red peony root) is not significantly reduced. Safflower and motherwort have certain effects in protecting brain tissue and reducing pathological damage, which may be related to their effects of promoting blood circulation and removing blood stasis, promoting diuresis and reducing swelling. The pathological changes in brain tissue of the drug-deficient groups (Example 9 lacks safflower and Example 10 lacks motherwort) are more serious than those of the complete formula groups.

[0110] Specific processing and processing methods are used for each raw material, such as removing impurities from Astragalus, separating large and small, washing, moistening, cutting into thick slices, and drying. This refined processing ensures the quality and efficacy of the raw materials, removes impurities, and makes the medicine pure. At the same time, through appropriate moistening and cutting, it is conducive to the decoction of effective ingredients or the role of effective ingredients in the preparation. Different medicines use different processing methods according to their own characteristics, which retains the effective ingredients of the medicine to the greatest extent and improves the quality and efficacy stability of the preparation. In the process of raw material pretreatment, strict compliance with standard operations ensures the consistency and standardization of each batch of raw materials, laying the foundation for the quality controllability of subsequent preparations. The processed raw pieces are spread flat on a stainless steel plate and dried at 70°C for 5 hours. This drying condition not only ensures that the microbial limit of the raw pieces meets the standard, but also makes the raw materials suitable for crushing, and the effective ingredients will not be destroyed due to excessive temperature. The sieving process of 100% of the drug powder passing through an 80-mesh sieve and 95% passing through a 100-mesh sieve makes the drug powder particle size uniform, increases the specific surface area of ​​the drug, is conducive to the dissolution, absorption and efficacy of the drug in the body, and also ensures the uniformity and stability of the preparation. A 15% starch slurry solution is selected as a binder, and the weight ratio of the drug powder to the starch slurry is 100:60. The drug pellets are prepared by a specific stirring time (10 minutes) and a hand feeling judgment standard (after uniform mixing, the hand feeling is moderately soft and hard, it is sticky when held, and slightly dispersed when loosened), which ensures the quality of the drug pellets, makes it have appropriate viscosity and plasticity, and is conducive to the subsequent pill making operation. During the pill making process, the tool and the strip outlet of the automatic pill making machine are accurately adjusted to make the particle size 4 mm, which ensures the uniformity of the specifications of the pills, which is conducive to the accurate control of the drug dosage and the patient's taking. The drying process is to first cool the pills in a clean area, then spread them out on trays, and dry them at 80°C for 5 hours using a hot air circulation drying method. This avoids the problems of cracking and deformation of the pills due to excessive drying or high temperature, and ensures the appearance and internal quality of the pills. The dried pills are polished in a water chestnut-type sugar coating machine, and an appropriate amount of purified water is added and gradually dried with hot and cold air to make the surface of the pills smooth and bright, which not only improves the appearance quality of the drugs, but also reduces the adhesion of the drugs during storage and administration, which is conducive to the preservation and use of the drugs. The connected pills and residual pills are selected in the manual pill selection process to ensure the appearance quality of the water pills. Subsequently, the inner packaging is strictly carried out in accordance with 10g per bag, and the difference in loading is controlled within ±4% of 10g required by the pharmacopoeia (9.6g-10.4g), and the "production date, preparation batch number, and expiration date" are accurately coded in the corresponding positions, as well as standardized outer packaging operations, to ensure the quality traceability and standardized production of the products, and to ensure the quality and safety of the preparations from all aspects.

[0111] In summary, the Chinese medicine preparation of the present invention has significant innovations in compatibility and preparation process. These innovations work together to give the preparation unique advantages and good application prospects in the treatment of diseases related to qi deficiency and blood stasis syndrome.

Claims

1. A Chinese medicine preparation of Longguigen Tongqiao Pills, characterized in that: The invention comprises the following raw materials in parts by weight: 210 parts of astragalus, 140 parts of angelica, 140 parts of kudzu root, 105 parts of chuanxiong, 70 parts of earthworm, 70 parts of salvia miltiorrhiza, 70 parts of red peony root, 70 parts of safflower and 105 parts of motherwort.

2. The Chinese medicine preparation according to claim 1, characterized in that The Chinese medicine preparation is in the form of pills, with each bag being equivalent to 9.2 g of the medicinal piece. The dosage is oral, 1 bag at a time, twice a day.

3. A method for preparing the Chinese medicine preparation according to claim 1, characterized in that: The following steps are involved: Raw material pretreatment: weigh each raw material accurately according to the formula, and prepare and process each raw material. Crushing: Spread the processed raw pieces of medicine on a stainless steel plate with a thickness of 1 cm, put them into an oven, and dry them at a temperature of 70°C for 5 hours, so that the microbial limit of the raw pieces of medicine meets the standard and is suitable for crushing. The dried raw pieces of medicine are mixed according to the prescription ratio and then crushed. 100% of the powder is sieved through an 80-mesh sieve, and 95% is sieved through a 100-mesh sieve to obtain a mixed powder; Preparation molding: Take the mixed drug powder, add 15% starch slurry solution as a binder, the weight ratio of drug powder to starch slurry is 100:60, cover the mixer cover and stir for 10 minutes, after mixing evenly, make a drug lump, add the drug lump to the automatic pill making machine, adjust the equipment knife and the outlet to make the particle size 4mm, make pills, and get pills. Spread the pills on the medicine receiving tray with a thickness of no more than 2cm, first cool in a clean area to harden the surface of the pellets, then spread them on the trays, use hot air circulation drying method, and dry them at 80℃ for 5 hours. The dried pills are loaded into a water chestnut-type sugar coating machine, purified water is added, and the hot and cold air of the sugar coating machine are turned on to gradually dry the moisture on the surface of the water pills. Polishing is performed until the surface of the pills is smooth. The method of manual pill selection is used to pick out the connected pills and the residual pills to ensure the appearance quality of the water pills. Then the inner packaging is carried out. The inner packaging is sealed using a water pill packaging machine. The inner packaging material is a medicinal composite film. Each bag is packaged with 10g. The difference in the filling amount is between ±4% of 10g as required by the pharmacopoeia. The pills are packed into the prepared outer packaging box according to the packaging specifications of the preparation to obtain the finished product.

4. Use of the Chinese medicine preparation according to claim 1 in the preparation of a drug for treating diseases related to Qi deficiency and blood stasis syndrome, wherein the diseases related to Qi deficiency and blood stasis syndrome include ischemic cerebrovascular disease.

5. A drug combination for treating diseases related to Qi deficiency and blood stasis syndrome, characterized in that: The invention comprises the Chinese medicine preparation according to claim 1 and a pharmaceutically acceptable excipient or carrier.

6. The pharmaceutical combination according to claim 5, characterized in that The drug combination also includes other drugs for treating ischemic cerebrovascular diseases, and the Chinese medicine preparation according to claim 1 has a synergistic effect when used in combination with other drugs.

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