Compound composition for treating cerebral hemorrhage, preparation method, application and medicine

Abstract

The invention provides a compound composition for treating cerebral hemorrhage, a preparation method, application and a medicine, and relates to the technical field of traditional Chinese medicines. The compound composition is prepared from the following raw materials in parts by weight: 10 to 30 parts of cortex moutan, 2 to 10 parts of radix et rhizoma rhei, 5 to 15 parts of herba lycopi, 10 to 21 parts of radix puerariae and 5 to 15 parts of loofah sponge. Mixing the moutan bark, the rheum officinale, the herba lycopi, the radix puerariae and the loofah sponge, and adding water for soaking; decocting twice, and combining filtrates to obtain the compound composition. The five medicines of moutan bark, rheum officinale, herba lycopi, radix puerariae and loofah sponge are adopted and are scientifically matched, so that the effects of remarkably improving brain microcirculation and promoting hematoma absorption are achieved; the hematoma volume can be obviously reduced, the inflammatory response is relieved, the brain tissue damage is relieved, and the treatment effective rate of cerebral hemorrhage is improved.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and particularly relates to a compound composition for treating cerebral hemorrhage, a preparation method, an application and a drug thereof. Background Art

[0002] Cerebrovascular diseases are common diseases that endanger human health. Cerebral hemorrhage is a cerebrovascular disease and is the second most common cause of stroke after ischemic stroke. The treatment of its acute stage is very important. At present, the treatment methods of Western medicine for cerebral hemorrhage mainly include two categories: surgical treatment and comprehensive medical treatment. Surgical treatment is mainly used for patients with large bleeding volume and surgical indications, which has certain risks; comprehensive medical treatment generally uses dehydrating agents to reduce cerebral edema, uses antihypertensive drugs to control blood pressure, prevent and treat infections, correct disorders of water and electrolyte and acid-base balance, or uses nerve cell function improvers and calcium channel blockers for treatment. However, the above treatment effects are not ideal.

[0003] Traditional Chinese medicine has certain applications in the treatment of drugs for cerebral hemorrhage, including using traditional Chinese medicine to improve symptoms, promote recovery, etc. Chinese invention patent CN101721572A discloses a traditional Chinese medicine compound preparation for treating hemorrhagic stroke. The preparation is prepared from the following raw materials in parts by weight: 2-30 g of rhubarb, 5-80 g of buffalo horn, 5-30 g of red peony root, 3-30 g of moutan bark, 5-50 g of rehmannia root, 3-30 g of pheretima, 1-20 g of notoginseng and 3-30 g of acorus tatarinowii; in the formula, rhubarb and buffalo horn are the monarch drugs. Rhubarb clears heat and purges fire, cools blood and removes stasis, and purges heat by way of the bowels. Buffalo horn has the function of clearing heat and cooling blood. The combination of the two drugs complements each other and can enhance the effect of cooling blood and removing stasis. Rehmannia root, moutan bark and red peony root are the ministerial drugs. The combination of the three drugs can better enhance the efficacy of the monarch drugs. Pheretima and notoginseng are used as adjuvants, and acorus tatarinowii is used to induce resuscitation and guide the drugs upward as the messenger drug. Each component in the various drugs cooperates with each other to have the effects of cooling blood and removing stasis, and purging heat by way of the bowels. However, the preparation does not disclose the therapeutic effect on accelerating the reduction of hematoma volume.

[0004] Chinese invention patent CN101513491A discloses a Chinese patent medicine for treating cardiovascular and cerebrovascular diseases, which can treat arteriosclerosis, cerebral hemorrhage, and sequelae of cerebral thrombosis. The raw materials of the Chinese patent medicine include: 8 - 12g of pangolin scales, 10 - 14g of ground beetles, 3 pieces of golden head centipedes 5 - 7 inches long, 13 - 17g of earthworms, 2 pieces of white flower snakes 3 - 7 inches long, 25 - 35g of white ginseng, 15 - 25g of Schisandra chinensis, 25 - 35g of Ophiopogon japonicus, 25 - 35g of Asparagus cochinchinensis, 25 - 35g of Fritillaria thunbergii, 18 - 24g of bitter almonds, 25 - 35g of Scutellaria baicalensis, 25 - 35g of Coptis chinensis, 25 - 35g of Gardenia jasminoides, 25 - 35g of Isatis indigotica, 25 - 35g of Cortex Fraxini, 18 - 24g of Yiyuan powder, 18 - 24g of Lithospermum erythrorhizon, 45 - 55g of raw gypsum, 45 - 55g of raw talc, 45 - 55g of efflorescent nitre, 25 - 35g of raw Rheum officinale, 25 - 35g of Achyranthes bidentata, 25 - 35g of Stauntonia chinensis, 25 - 35g of Cinnamomum cassia, 18 - 24g of ephedra root, 25 - 35g of liquorice, 13 - 17g of Angelica sinensis, 13 - 17g of saffron, 13 - 17g of Panax notoginseng, 18 - 22g of Rubia cordifolia, 45 - 55g of raw Rehmannia glutinosa, 45 - 55g of Paeonia suffruticosa, 45 - 55g of Paeonia lactiflora, 35 - 45g of Sappanwood, 45 - 55g of Poria cocos, and 2 taels of Luffa cylindrica. The Chinese patent medicine has as many as 37 components, with a complex formula composition and may have certain toxicity.

[0005] Chinese invention patent CN104189115A discloses a traditional Chinese medicine for the recovery period of cerebral hemorrhage. By weight, it includes the following raw material components: 20 - 30 parts of Salvia miltiorrhiza, 10 - 20 parts of Ligusticum chuanxiong, 10 - 20 parts of Paeonia suffruticosa, 10 - 20 parts of Acanthopanax senticosus, 10 - 20 parts of Rheum officinale, 10 - 20 parts of Hirudo, 20 - 30 parts of white flower snake, 15 - 20 parts of Angelica sinensis, 10 - 20 parts of Gentiana macrophylla, 10 - 20 parts of Notopterygium incisum, 10 - 20 parts of Saposhnikovia divaricata, and 10 - 15 parts of Erigeron breviscapus. The traditional Chinese medicine has a certain effect on the treatment of medium - and long - term cerebral hemorrhage, but has a weak treatment effect on acute - phase cerebral hemorrhage.

[0006] At present, the traditional Chinese medicine formula for treating cerebral hemorrhage has complex components, and most of them do not show the effect of synergistic enhancement. The effects of reducing hematoma volume and clearing heat and cooling blood are weak. In addition, there are few traditional Chinese medicine formulas for treating the acute phase of cerebral hemorrhage caused by blood heat, and there is no report on using Cortex Moutan as the monarch drug to treat cerebral hemorrhage. Based on this, it is necessary to further study the types and ratios of components of traditional Chinese medicine formulas to provide a traditional Chinese medicine compound composition with a concise formula, where each component interacts and synergistically enhances the effect, significantly reducing the hematoma volume, improving the efficacy of treating cerebral hemorrhage, and being safe and non - toxic. Summary of the Invention

[0007] In view of the problems existing in the prior art, the present invention provides a compound composition for treating cerebral hemorrhage, a preparation method, an application, and a drug thereof. The present invention uses five traditional Chinese medicines, namely Cortex Moutan, Radix et Rhizoma Rhei, Herba Lycopi, Radix Puerariae, and Retinervus Luffae Fructus, for scientific compatibility to achieve the effects of clearing heat, cooling blood, promoting blood circulation, and detumescence. The compound composition of the present invention can improve cerebral microcirculation, promote hematoma absorption, significantly reduce the hematoma volume, alleviate inflammatory reactions, reduce brain tissue damage, and improve the treatment efficiency, especially the treatment efficiency for the acute stage of cerebral hemorrhage.

[0008] To achieve the above object, the technical solution adopted by the present invention is as follows: First, the present invention provides a compound composition for treating cerebral hemorrhage. Calculated by weight, the raw materials are composed of the following components: 10 - 30 parts of Cortex Moutan, 2 - 10 parts of Radix et Rhizoma Rhei, 5 - 15 parts of Herba Lycopi, 10 - 21 parts of Radix Puerariae, and 5 - 15 parts of Retinervus Luffae Fructus.

[0009] Preferably, for the compound composition, calculated by weight, the raw materials are composed of the following components: 15 - 25 parts of Cortex Moutan, 3 - 8 parts of Radix et Rhizoma Rhei, 8 - 12 parts of Herba Lycopi, 13 - 17 parts of Radix Puerariae, and 6 - 12 parts of Retinervus Luffae Fructus.

[0010] More preferably, for the compound composition, calculated by weight, the raw materials are composed of the following components: 20 parts of Cortex Moutan, 5 parts of Radix et Rhizoma Rhei, 10 parts of Herba Lycopi, 15 parts of Radix Puerariae, and 9 parts of Retinervus Luffae Fructus.

[0011] Then, the present invention provides a preparation method for the above compound composition, including the steps: (1) Mix Cortex Moutan, Radix et Rhizoma Rhei, Herba Lycopi, Radix Puerariae, and Retinervus Luffae Fructus, and soak them in water to obtain a composition; (2) First decoction: Boil the mixture in step (1), then decoct it, and filter to obtain filtrate 1 and medicinal residues; (3) Second decoction: Boil the medicinal residues in step (2) in water, then decoct it, and filter to obtain filtrate 2; (4) Combine filtrate 1 and filtrate 2 to obtain the compound composition.

[0012] Preferably, in step (1), for the water soaking, the amount of added water covers the raw material components, and soak at room temperature for 30 - 60 min.

[0013] More preferably, in step (1), the soaking time is 40 - 50 min.

[0014] Even more preferably, in step (1), the soaking time is 45 min.

[0015] Preferably, in step (2), the decocting time is 20 - 30 min.

[0016] Further preferably, in step (2), the decocting time is 25 min.

[0017] Preferably, in step (3), the decocting time is 15 - 25 min.

[0018] Further preferably, in step (3), the decocting time is 20 min.

[0019] Preferably, in steps (2) and (3), the filtration is hot filtration.

[0020] In the present invention, during the soaking and decocting processes, the solid - liquid ratio of the traditional Chinese medicine raw materials and water is controlled at 1:10 - 20 g / mL.

[0021] Furthermore, the present invention provides the use of the above - mentioned compound composition in the preparation of a medicament for treating cerebral hemorrhage.

[0022] Finally, the present invention provides a medicament for treating cerebral hemorrhage, comprising: the above - mentioned compound composition.

[0023] Preferably, the medicament is specifically a medicament for treating the heat syndrome that appears in the acute stage of cerebral hemorrhage.

[0024] Preferably, the medicament is specifically a medicament for promoting hematoma absorption and reducing hematoma volume.

[0025] Further preferably, the medicament is specifically a medicament for promoting cerebral hematoma absorption and reducing cerebral hematoma volume.

[0026] Preferably, the components of the medicament may further include: a pharmaceutical carrier. The pharmaceutical carrier can be solid, liquid or gas. Examples of solid carriers include lactose, kaolin, sucrose, talc, gelatin, agar, pectin, gum arabic, magnesium stearate and stearic acid. Examples of liquid carriers include syrup, peanut oil, olive oil and water. Examples of gas carriers include carbon dioxide and nitrogen.

[0027] When preparing the composition of an oral dosage form, any convenient pharmaceutical medium can be used. For example, water, ethanol, oil, alcohol, flavoring agents, preservatives, coloring agents, etc. can be used to form oral liquid preparations such as suspensions and solutions; while carriers such as starch, sugars, microcrystalline cellulose, diluents, granulating agents, emulsifiers, lubricants, binders, disintegrants can be used to form oral solid preparations such as powders, capsules and tablets. Due to their easy administration, tablets and capsules are preferred oral dosage units using solid pharmaceutical carriers. Coating of tablets can be carried out using standard aqueous or non - aqueous techniques.

[0028] Tablets containing the Chinese medicinal composition or extract of the present invention can be prepared by tabletting or molding, and one or more auxiliary ingredients or adjuvants can be optionally used. Tablets can be prepared by tabletting the active ingredient in a free-flowing form (such as powder or granules) in a suitable machine, optionally mixed with binders, lubricants, inert diluents, surface-active substances or dispersing agents. Molded tablets can be molded in a suitable machine, i.e., a powdered compound mixture moistened with an inert liquid diluent. Each tablet preferably contains about 0.05 mg to about 5 g of the active ingredient, and each sachet or capsule preferably contains about 0.05 mg to about 5 g of the active ingredient. For example, a preparation intended for oral administration to humans may contain about 0.5 mg to about 5 g of the active drug, mixed with a suitable and convenient carrier material, which may account for about 5% to 95% of the total composition. The unit dosage form usually contains about 1 mg to about 2 g of the active ingredient, usually 25 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 800 mg or 1000 mg.

[0029] The pharmaceutical composition suitable for parenteral administration in the present invention can be prepared as an aqueous solution or suspension of the active compound. Appropriate surfactants can be included, such as hydroxypropyl cellulose. Dispersions can also be prepared in glycerol, liquid polyethylene glycol and mixtures of their oils. In addition, preservatives can be added to prevent the harmful growth of microorganisms.

[0030] The drugs of the present invention can be in a form suitable for topical use, such as aerosols, creams, ointments, lotions, powders or the like. In addition, the composition can be in a suitable form for transdermal delivery devices. The Chinese medicinal composition of the present invention can be used to prepare these formulations by conventional processing methods. For example, creams or ointments with the desired consistency can be prepared by mixing hydrophilic materials and water, and about 5 wt% to about 10 wt% of the compound.

[0031] The drugs of the present invention can be in a form suitable for rectal administration, where the carrier is solid. It is preferably to make the mixture into unit-dose suppositories. Suitable carriers include cocoa butter and other commonly used materials in the art. Suppositories can be prepared by first forming a composition containing a softened or melted carrier, and then cooling and shaping in a mold.

[0032] In addition to the above carrier components, the above pharmaceutical preparations may include (if applicable) one or more additional carrier components, such as diluents, buffers, flavoring agents, binders, surface-active substances, thickeners, lubricants, preservatives (including antioxidants), etc. In addition, other excipients can be added, such as lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, etc., coloring agents and flavoring agents, etc. To make the preparation isotonic with the blood of the intended recipient. Components containing the Chinese medicinal composition of the present invention can also be prepared in powder or concentrated solution form.

[0033] Preferably, the dosage form of the drug is not limited to dosage forms for administration such as pills, capsules, granules, oral liquids, powders, tablets, lozenges, ointments, etc., and suitable pharmaceutical carriers in the art can be selected according to different dosage forms.

[0034] In the compound composition of the present invention, Cortex Moutan is used as the monarch drug, Rheum palmatum is used as the minister drug, Eupatorium japonicum and Pueraria lobata are used as assistant drugs, and Luffa cylindrica is used as the messenger drug. The five herbs are combined to have the effects of clearing heat, cooling blood, promoting blood circulation and detumescence, and are mainly used for treating the acute stage of cerebral hemorrhage caused by heat syndrome. The basic pathogenesis of cerebral hemorrhage is the disorder of zang-fu functions, the imbalance of yin and yang, the reverse disorder of qi and blood, which attacks the brain upward, and the collateral is broken and the blood overflows outside the cerebral vessels. In severe cases, it can block the clear orifices and obscure the mind. The acute stage of cerebral hemorrhage is caused by different reasons. "Wind syndrome", "heat syndrome", "phlegm syndrome", and "yin deficiency syndrome" are the basic syndromes in the acute stage of hemorrhagic stroke. "Wind syndrome" is the initiating factor of the disease, and "heat syndrome" is the most obvious in the acute stage, while "stasis syndrome" runs through the whole course of the disease. The compound composition of the present invention is mainly used for treating the heat syndrome in the acute stage of cerebral hemorrhage. For the symptoms of blood heat running amok, attacking the brain upward, and blood overflowing outside the vessels, it can achieve the unity of the ideas of theory, method, formula and medicine. By clearing heat, cooling blood, promoting blood circulation and detumescence, it can eliminate the heat syndrome and treat concurrent syndromes at the same time.

[0035] Cortex Moutan: Bitter, pungent, slightly cold; attributing to the heart, liver and kidney meridians; having the functions of cooling blood and clearing heat, promoting blood circulation and removing stasis. Modern research has proved that Cortex Moutan mainly contains chemical components such as paeonol, and has various pharmacological effects such as protecting the liver and kidney, anti-inflammatory, sedative, cooling, antipyretic, analgesic, and antispasmodic. It is mainly used for treating heat entering nutrient blood, epidemic febrile disease with maculae, hematemesis and epistaxis, feverish sensation in the evening with early morning coolness, anhidrotic osteopyrexia, amenorrhea and dysmenorrhea, traumatic injury, carbuncles and sores. "Compendium of Materia Medica": "Cortex Moutan treats the latent fire in the blood of the heart, liver, spleen and kidney meridians of the hands and feet." "Explanation of the Classic of Materia Medica": "Cortex Moutan is bitter and slightly pungent in taste, cold in nature and non-toxic. Pungency can disperse stasis and accumulation, and bitter cold can remove blood heat. It enters the blood aspect and is an important drug for cooling blood heat. Cold and heat are the symptoms of yin deficiency and blood heat. Stroke with spasm, convulsion, epilepsy are all due to yin deficiency and internal heat, and insufficient nutrient blood. When heat is removed, the blood becomes cool, and when it is cool, new blood is generated and yin qi is restored. When yin qi is restored, the fire does not flare up and there is no syndrome of wind generated due to heat, so it can all be mainly treated. Carbuncles and sores are caused by heat congestion and blood stasis." For the disease of blood heat running amok in the acute stage of cerebral hemorrhage, Cortex Moutan can directly treat the cause through the effects of cooling blood and clearing heat, promoting blood circulation and removing stasis. The present invention selects Cortex Moutan as the monarch drug.

[0036] Rhubarb: Bitter in taste and cold in nature; it has the effects of purging accumulation, clearing heat and purging fire, cooling blood and detoxifying, removing stasis and dredging channels. It is mainly used to treat constipation due to accumulation, epistaxis due to blood heat, red eyes and sore throat, hot toxic sores, burns and scalds, various stasis syndromes, damp-heat dysentery, jaundice, and stranguria syndrome. "Shennong Ben Cao Jing": It can remove stasis in the lower energizer, relieve blood stasis and cold and heat, break up masses and accumulations, eliminate retained fluid and stagnant food, cleanse the intestines and stomach, promote the old and bring forth the new, promote the passage of water and grains, regulate the middle energizer and transform food, and harmonize the five zang-organs. Rhubarb can clear heat and purge fire, cool blood and detoxify, and assist the monarch drug Cortex Moutan to enhance its effects of clearing heat and cooling blood, helping to reduce the inflammatory reaction and hot toxic symptoms in the acute stage of cerebral hemorrhage. In addition, rhubarb can also help discharge stasis and toxins in the body through its purging effect, contributing to the recovery of the condition. In the present invention, rhubarb is selected as the ministerial drug.

[0037] Eupatorium japonicum Thunb.: Bitter, pungent, and slightly warm; it pertains to the liver and spleen meridians; it has the effects of promoting blood circulation and regulating menstruation, removing stasis and dissipating carbuncles, and promoting diuresis and reducing edema. It is mainly used to treat irregular menstruation, amenorrhea, dysmenorrhea, postpartum blood stasis abdominal pain, sores and carbuncles, and ascites due to edema. "Compendium of Materia Medica": It can nourish nutrient qi, break up stagnant blood, and is the main drug for treating women's fatigue and emaciation, and is an important drug in gynecology. Eupatorium japonicum Thunb. can assist Cortex Moutan to strengthen the effect of promoting blood circulation and removing stasis. Considering that cerebral hemorrhage in the acute stage is often accompanied by edema, the effects of Eupatorium japonicum Thunb. in removing stasis and dissipating carbuncles, and promoting diuresis and reducing edema are utilized to treat the concurrent syndrome of edema. In the present invention, Eupatorium japonicum Thunb. is selected as the adjuvant drug.

[0038] Kudzu Root: Sweet, pungent, and cool in taste; it pertains to the spleen, stomach, and lung meridians; it has the effects of relieving muscle spasms and reducing fever, promoting eruption, promoting fluid production to quench thirst, ascending yang to stop diarrhea, dredging channels and collaterals, and relieving alcohol toxicity. It is mainly used to treat exogenous fever and headache, stiffness and pain in the nape and back, thirst, wasting-thirst, failure of measles to erupt, heat dysentery, diarrhea, dizziness and headache, hemiplegia due to stroke, chest impediment and heart pain, and alcohol poisoning. "Explanation of the Canon of Materia Medica": "Kudzu Root is the main drug for dispelling pathogenic heat in Yangming meridian of epidemic febrile disease, so it is mainly used to treat wasting-thirst, high fever of the body, and vomiting due to heat congestion in the chest and diaphragm. Its property of dispersing and ascending is the nature of wind drugs, so it is mainly used to treat various arthralgias". Kudzu Root can lead the drug upward to the head, strengthening the therapeutic effect of the monarch drug and ministerial drug on the brain lesion, and at the same time also helps to relieve the symptoms of fever and headache in patients with cerebral hemorrhage, and improve cerebral blood circulation. In the present invention, Kudzu Root is selected as the adjuvant drug.

[0039] Luffa cylindrica (L.) Roem.: Sweet in taste and neutral in nature; it pertains to the stomach, lung, and liver meridians. It has the effects of expelling wind, dredging collaterals, promoting blood circulation, and inducing lactation. It is mainly used to treat arthralgia and contracture, distending pain in the chest and hypochondrium, failure of lactation, and breast abscess and swelling pain. "Materia Medica for Easy Reading": "Luffa cylindrica (L.) Roem. enters the meridians and collaterals and dispels pathogenic heat. When the heat is removed, the wind will go away, and the body fluids in the collaterals will not combine to form phlegm and turn into various swelling and toxic symptoms, so it is said to detoxify". "New Compilation of Materia Medica": "Dredge the meridians and collaterals, harmonize the blood vessels, resolve phlegm and regulate qi". Luffa cylindrica (L.) Roem., with its property of dredging collaterals, plays the role of guiding the drug directly to the diseased site and harmonizing various drugs, enabling the prescription to better exert the effects of clearing heat, cooling blood, promoting blood circulation, and reducing swelling. Luffa cylindrica (L.) Roem. is the guiding drug in the present invention's formula composition.

[0040] Compared with the prior art, the present invention has the following beneficial effects: 1. The compound composition of the present invention uses Cortex Moutan as the monarch drug, Rheum officinale as the minister drug, Eupatorium japonicum Thunb. and Pueraria lobata (Willd.) Ohwi as the assistant drugs, and Fructus Luffae as the courier drug. The above five herbs are combined in compatibility. Each component interacts with each other, complements each other, and the formula is concise. The composition is prepared in a specific ratio, bringing significant effects of clearing heat, cooling blood, promoting blood circulation, and detumescence. The compound composition of the present invention has good therapeutic efficacy for the heat syndrome that appears in the acute stage of cerebral hemorrhage, can promote the absorption of hematoma, improve the compression of the surrounding brain tissue by the hematoma, and thus improve the prognosis of patients.

[0041] 2. The compound composition of the present invention is prepared by the method of decocting multiple times, so that the active ingredients are fully dissolved, the content of the efficacy components is increased, and it brings the effect of significantly reducing the volume of the hematoma.

[0042] 3. The compound composition of the present invention is used for treating cerebral hemorrhage caused by heat syndrome and has definite curative effect in clinical practice. The compound composition of the present invention is different from other reported prescriptions for treating cerebral hemorrhage. The compound composition of the present invention can be used for the acute stage of cerebral hemorrhage caused by heat syndrome, while most of the traditional Chinese medicine prescriptions disclosed in the prior art are used for the recovery stage of cerebral hemorrhage; the compound composition of the present invention has a wider applicability. Detailed implementation manners

[0043] The following non-limiting examples can enable those of ordinary skill in the art to understand the present invention more comprehensively, but do not limit the present invention in any way. The following content is only an exemplary illustration of the scope claimed by the present invention. Those skilled in the art can make various changes and modifications to the present invention according to the disclosed content, and it should also fall within the scope claimed by the present invention.

[0044] When the examples give numerical ranges, it should be understood that unless otherwise specified in the present invention, both endpoints of each numerical range and any value between the two endpoints can be selected. Unless otherwise defined, all technical and scientific terms used in the present invention have the same meaning as commonly understood by those of ordinary skill in the technical field to which the present invention belongs.

[0045] The present invention will be further described below by way of specific examples. All kinds of chemical reagents and traditional Chinese medicine raw materials used in the examples of the present invention are obtained through conventional commercial channels unless otherwise specified.

[0046] Example 1 A compound composition for treating cerebral hemorrhage, the raw materials by weight are: 20 parts of Cortex Moutan, 5 parts of Rheum officinale, 10 parts of Eupatorium japonicum Thunb., 15 parts of Pueraria lobata (Willd.) Ohwi, and 9 parts of Fructus Luffae.

[0047] The preparation method of the compound composition is: (1) Mix Cortex Moutan, Radix et Rhizoma Rhei, Herba Lycopi, Radix Puerariae, and Retinervus Luffae together, add water to submerge the raw materials by 3 - 5 cm (solid - liquid ratio is 1:15 g / mL), and soak at room temperature for 45 minutes to obtain a mixture; (2) First decoction: Boil the mixture obtained in step (1), then decoct for 25 minutes, and filter while it is hot to obtain filtrate 1 and medicinal residues; (3) Second decoction: Add water to the medicinal residues obtained in step (2) to submerge the residues by 3 - 5 cm (solid - liquid ratio is 1:15 g / mL), boil, and then decoct for 20 minutes, and filter while it is hot to obtain filtrate 2; (4) Combine filtrate 1 and filtrate 2 to obtain the compound composition.

[0048] Example 2 A compound composition for treating cerebral hemorrhage, the raw materials by weight are: 15 parts of Cortex Moutan, 3 parts of Radix et Rhizoma Rhei, 8 parts of Herba Lycopi, 13 parts of Radix Puerariae, and 6 parts of Retinervus Luffae.

[0049] The rest are the same as in Example 1.

[0050] Example 3 A compound composition for treating cerebral hemorrhage, the raw materials by weight are: 25 parts of Cortex Moutan, 8 parts of Radix et Rhizoma Rhei, 12 parts of Herba Lycopi, 17 parts of Radix Puerariae, and 12 parts of Retinervus Luffae.

[0051] The rest are the same as in Example 1.

[0052] Example 4 A compound composition for treating cerebral hemorrhage, the raw materials by weight are: 10 parts of Cortex Moutan, 2 parts of Radix et Rhizoma Rhei, 5 parts of Herba Lycopi, 10 parts of Radix Puerariae, and 5 parts of Retinervus Luffae.

[0053] The preparation method of the compound composition is as follows: (1) Mix Cortex Moutan, Radix et Rhizoma Rhei, Herba Lycopi, Radix Puerariae, and Retinervus Luffae together, add water to submerge the raw materials by 3 - 5 cm (solid - liquid ratio is 1:15 g / mL), and soak at room temperature for 30 minutes to obtain a mixture; (2) First decoction: Boil the mixture obtained in step (1), then decoct for 30 minutes, and filter while it is hot to obtain filtrate 1 and medicinal residues; (3) Second decoction: Add water to the medicinal residues obtained in step (2) to submerge the residues by 3 - 5 cm (solid - liquid ratio is 1:15 g / mL), boil, and then decoct for 25 minutes, and filter while it is hot to obtain filtrate 2; (4) Combine filtrate 1 and filtrate 2 to obtain the compound composition.

[0054] Example 5 A compound composition for treating cerebral hemorrhage, the raw materials by weight are: 30 parts of Cortex Moutan, 10 parts of Radix et Rhizoma Rhei, 15 parts of Herba Lycopi, 21 parts of Radix Puerariae, and 15 parts of Retinervus Luffae.

[0055] The preparation method of the compound composition is as follows: (1) Mix Cortex Moutan, Rheum officinale, Eupatorium japonicum Thunb., Pueraria lobata (Willd.) Ohwi and Luffa cylindrica (L.) Roem., add water to submerge the raw materials by 3 - 5 cm (solid - liquid ratio is 1:15 g / mL), soak at room temperature for 60 min to obtain a mixture; (2) First decoction: Boil the mixture in step (1), then decoct for 20 min, filter while it is hot to obtain filtrate 1 and medicinal residues; (3) Second decoction: Add water to the medicinal residues in step (2) to submerge the medicinal residues by 3 - 5 cm (solid - liquid ratio is 1:15 g / mL), boil, then decoct for 15 min, filter while it is hot to obtain filtrate 2; (4) Combine filtrate 1 and filtrate 2 to obtain the compound composition.

[0056] Comparative Example 1 Different from Example 1, the ministerial drug Rheum officinale is replaced with Radix Paeoniae Rubra.

[0057] The raw materials of the compound composition, by weight, are: 20 parts of Cortex Moutan, 5 parts of Radix Paeoniae Rubra, 10 parts of Eupatorium japonicum Thunb., 15 parts of Pueraria lobata (Willd.) Ohwi and 9 parts of Luffa cylindrica (L.) Roem.

[0058] The preparation method of the compound composition is as follows: (1) Mix Cortex Moutan, Radix Paeoniae Rubra, Eupatorium japonicum Thunb., Pueraria lobata (Willd.) Ohwi and Luffa cylindrica (L.) Roem., add water to submerge the raw materials by 3 - 5 cm (solid - liquid ratio is 1:15 g / mL), soak at room temperature for 45 min to obtain a mixture; (2) First decoction: Boil the mixture in step (1), then decoct for 25 min, filter while it is hot to obtain filtrate 1 and medicinal residues; (3) Second decoction: Add water to the medicinal residues in step (2) to submerge the medicinal residues by 3 - 5 cm (solid - liquid ratio is 1:15 g / mL), boil, then decoct for 20 min, filter while it is hot to obtain filtrate 2; (4) Combine filtrate 1 and filtrate 2 to obtain the compound composition.

[0059] Comparative Example 2 Different from Example 1, the dosage ratio of each raw material component in the compound composition is different.

[0060] The raw materials of the compound composition, by weight, are: 8 parts of Cortex Moutan, 1 part of Rheum officinale, 25 parts of Eupatorium japonicum Thunb., 22 parts of Pueraria lobata (Willd.) Ohwi and 3 parts of Luffa cylindrica (L.) Roem. The preparation method of the compound composition is the same as that of Example 1.

[0061] Comparative Example 3 Different from Example 1, the raw material components of the compound composition are different.

[0062] Compound composition, the raw materials by weight are: 20 parts of Cortex Moutan, 5 parts of Rheum officinale, and 9 parts of Luffa cylindrica

[0063] The preparation method of the compound composition is as follows: (1) Mix Cortex Moutan, Rheum officinale, and Luffa cylindrica, add water to submerge the raw materials by 3 - 5 cm (solid - liquid ratio is 1:15 g / mL), soak at room temperature for 45 min to obtain a mixture; (2) First decoction: Boil the mixture in step (1), then decoct for 25 min, filter while it is hot to obtain filtrate 1 and medicinal residues; (3) Second decoction: Add water to the medicinal residues in step (2) to submerge the medicinal residues by 3 - 5 cm (solid - liquid ratio is 1:15 g / mL), boil, then decoct for 20 min, filter while it is hot to obtain filtrate 2; (4) Combine filtrate 1 and filtrate 2 to obtain the compound composition.

[0064] Comparative Example 4 Different from Example 1, the raw material components of the compound composition are different.

[0065] Compound composition, the raw materials by weight are: 10 parts of Eupatorium japonicum Thunb. and 15 parts of Pueraria lobata (Willd.) Ohwi.

[0066] The preparation method of the compound composition is as follows: (1) Mix Eupatorium japonicum Thunb. and Pueraria lobata (Willd.) Ohwi., add water to submerge the raw materials by 3 - 5 cm (solid - liquid ratio is 1:15 g / mL), soak at room temperature for 45 min to obtain a mixture; (2) First decoction: Boil the mixture in step (1), then decoct for 25 min, filter while it is hot to obtain filtrate 1 and medicinal residues; (3) Second decoction: Add water to the medicinal residues in step (2) to submerge the medicinal residues by 3 - 5 cm (solid - liquid ratio is 1:15 g / mL), boil, then decoct for 20 min, filter while it is hot to obtain filtrate 2; (4) Combine filtrate 1 and filtrate 2 to obtain the compound composition.

[0067] Comparative Example 5 Different from Example 1, the preparation method of the compound composition is different. Specifically: Mix Cortex Moutan, Rheum officinale, Eupatorium japonicum Thunb., Pueraria lobata (Willd.) Ohwi., and Luffa cylindrica, add water to submerge the raw materials by 3 - 5 cm (solid - liquid ratio is 1:15 g / mL), boil, then decoct for 45 min, filter while it is hot to obtain the filtrate.

[0068] Experiment 1 Clinical Efficacy Comparison 110 patients with cerebral hemorrhage, aged 40 - 65 years (average age 52.9 years), were randomly divided into 11 groups, with 10 patients in each group, namely: control group, Example 1 group, Example 2 group, Example 3 group, Example 4 group, Example 5 group, Comparative Example 1 group, Comparative Example 2 group, Comparative Example 3 group, Comparative Example 4 group, Comparative Example 5 group; all groups except the control group were experimental groups. There were no statistically significant differences in the gender, age, comorbidities, etc. of the patients in each group (P > 0.05), and they were comparable.

[0069] Inclusion criteria for patients with cerebral hemorrhage: (1) The onset time of the patient < 14 days (acute phase); (2) All patients underwent cranial CT examination by a dedicated person in the imaging department, and it was confirmed that there were intracranial hematomas of varying degrees; (3) No serious primary diseases or mental illnesses in the heart, liver, lungs, kidneys, blood system, etc.; (4) All patients underwent consultation by a surgical expert, and the condition was explained to the family members. The family members refused surgical treatment and signed the informed consent form.

[0070] Experimental ethics number: Lin Yan Shen

[2018] No. 075 (Ethics Committee of Xuanwu Hospital, Capital Medical University).

[0071] The patients in the control group did not take the relevant compound composition, and the control group was given 20% mannitol injection (125 mL) for dehydration and reducing intracranial pressure; the patients in the example and comparative example groups took the compound composition (filtrate) of each group respectively. The filtrates obtained in each example and comparative example were concentrated under pressure so that the concentration of the active ingredient in the filtrate was 60 g:400 mL. The patients with cerebral hemorrhage drank 400 mL of the compound composition (prepared from 60 g of the active ingredient) every day.

[0072] 1. Comparison of hematoma size Cranial CT evaluation: The hematoma volume of the patients was detected before treatment; after continuous administration of the compound composition for 2 weeks, the hematoma volume was detected. The comparison of the results of the hematoma volume before and after treatment is shown in Table 1.

[0073] SPSS 26.0 was used for statistics. Measurement data were expressed as mean ± standard error (x ± se). Paired sample t - test was used for within - group comparison before and after treatment, and independent sample t - test was used for between - group comparison; chi - square test was used for count data. P < 0.05 was considered statistically significant.

[0074] Table 1

[0075] In Table 1, for the data in the same column, when comparing the experimental groups with the control group, ## P < 0.01, # P < 0.05, showing statistically significant differences; for the data in the same row, when comparing after treatment with before treatment, && P < 0.01,& P < 0.05, showing a statistically significant difference.

[0076] As can be seen from the comparison of the technical effects in Table 1, the compound composition of the embodiments of the present invention can accelerate the reduction of the hematoma volume, and the effect of reducing the hematoma volume is significantly better than that of the comparative examples and the control group.

[0077] In Comparative Example 1, the ministerial drug used was Paeonia lactiflora Pall., taking its effect of clearing heat and cooling blood. Although it can play a certain role in relieving the edema of patients with cerebral hemorrhage clinically, compared with the compound composition of the embodiments of the present invention, Rheum officinale Baill. can better assist the monarch drug Cortex Moutan to enhance its efficacy of clearing heat and cooling blood. At the same time, Rheum officinale Baill. can help reduce the inflammatory reaction and heat-toxicity symptoms of cerebral hemorrhage through its purgative effect. In the clinical result observation, the compound composition with Rheum officinale Baill. as the ministerial drug can enable the hematoma volume of patients to shrink faster.

[0078] The formula of the embodiment can relieve the symptoms of clinical cerebral hemorrhage patients faster and the hematoma absorption speed is also faster compared with Comparative Example 2 with changed formula ratio.

[0079] In Comparative Example 3, 3 components were used to prepare the compound composition, and in Comparative Example 4, 2 components were used to prepare the compound composition. At the same dose of the raw materials, even if the effects of reducing the hematoma volume of Comparative Example 3 and Comparative Example 4 are added together, the effect of significantly reducing the hematoma volume described in the present invention is still not achieved. Therefore, the 5 components of the present invention interact with each other and are used in synergistic cooperation, bringing a synergistic effect of reducing the hematoma volume.

[0080] In Comparative Example 5, the preparation method of the compound composition was changed. Although it has a certain effect of reducing the hematoma volume, there is still a large difference compared with the embodiment.

[0081] 2. Comparison of NIHSS scores Comparison of NIHSS scores: After the patients took the compound composition continuously for 2 weeks before and after treatment, the National Institutes of Health Stroke Scale (NIHSS) scores were performed. The scoring items were: level of consciousness, questions about the level of consciousness, commands for the level of consciousness, gaze, visual field, facial palsy, upper limb movement, lower limb movement, limb ataxia, sensation, language, dysarthria, neglect. The criteria for NIHSS scores are shown in Table 2.

[0082] Table 2

[0083] The NIHSS score results before and after treatment are shown in Table 3, and the score results are expressed in the form of mean ± standard error (x ± se).

[0084] Table 3

[0085] In Table 3, for the data in the same column, compared with the control group, each experimental group ## P < 0.01, # P < 0.05, showing statistical differences; for the data in the same row, compared with before treatment, && P < 0.01, & P < 0.05, showing statistical differences.

[0086] It can be seen from the comparison of the technical effects in Table 3 that the compound composition of the embodiment of the present invention can significantly reduce the NIHSS score, and the scoring results are significantly better than those of the comparative example and the control group.

[0087] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than limiting the protection scope of the present invention. Any simple modification or equivalent replacement of the technical solution of the present invention by those of ordinary skill in the art shall not depart from the essence and scope of the technical solution of the present invention.

Claims

1. A compound composition for treating cerebral hemorrhage, characterized in that, By weight, the raw materials consist of the following components: 10-30 parts of Cortex Moutan, 2-10 parts of Rheum officinale, 5-15 parts of Lycopus lucidus Turcz., 10-21 parts of Pueraria lobata (Willd.) Ohwi, and 5-15 parts of Luffa cylindrica (L.) Roem.

2. The compound composition according to claim 1, wherein By weight, the raw materials consist of the following components: 15-25 parts of Cortex Moutan, 3-8 parts of Rheum officinale, 8-12 parts of Lycopus lucidus Turcz., 13-17 parts of Pueraria lobata (Willd.) Ohwi, and 6-12 parts of Luffa cylindrica (L.) Roem.

3. The compound composition according to claim 2, wherein By weight, the raw materials consist of the following components: 20 parts of Cortex Moutan, 5 parts of Rheum officinale, 10 parts of Lycopus lucidus Turcz., 15 parts of Pueraria lobata (Willd.) Ohwi, and 9 parts of Luffa cylindrica (L.) Roem.

4. The preparation method of the compound composition according to any one of claims 1-3, characterized in that, It includes the steps: (1) Mix Cortex Moutan, Rheum officinale, Lycopus lucidus Turcz., Pueraria lobata (Willd.) Ohwi, and Luffa cylindrica (L.) Roem., soak them in water to obtain a mixture. (2) First decoction: Boil the mixture in step (1), then decoct it and filter to obtain filtrate 1 and medicinal residues. (3) Second decoction: Boil the medicinal residues in step (2) in water, then decoct it and filter to obtain filtrate 2. (4) Combine filtrate 1 and filtrate 2 to obtain a compound composition.

5. The preparation method according to claim 4, characterized in that, In step (1), for the water soaking, the amount of added water covers the raw material components, and soak at room temperature for 30-60 min.

6. The preparation method according to claim 4, characterized in that, In step (2), the decocting time is 20-30 min; in step (3), the decocting time is 15-25 min.

7. Use of the compound composition in the preparation of a medicament for treating cerebral hemorrhage, characterized in that, The compound composition in the said application is the compound composition described in any one of claims 1-3 or the compound composition prepared by the preparation method described in any one of claims 4-6.

8. A drug for treating cerebral hemorrhage, characterized in that, It includes: The compound composition described in any one of claims 1-3 or the compound composition prepared by the preparation method described in any one of claims 4-6.

9. The medicament according to claim 8, wherein The said drug is specifically a drug for treating heat syndrome in the acute stage of cerebral hemorrhage.

10. The drug according to claim 8, characterized in that, The said drug is specifically a drug for promoting hematoma absorption and reducing hematoma volume.

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