A traditional Chinese medicine composition for clearing away heat, removing blood stasis, stopping bleeding and regulating menstruation and its preparation method

Abstract

The present invention provides a traditional Chinese medicine composition for clearing heat, removing blood stasis, stopping bleeding and regulating menstruation, and a preparation method thereof, relating to the technical field of traditional Chinese medicine. The traditional Chinese medicine composition of the present invention comprises the following components: catalpol, aucubin, β-sitosterol, emodin, chrysophanol, sanguisorba officinalis extract, Panax notoginseng saponins, septamine, cuttlefish scaly, rubiacin, typhaneuroside, and p-coumaric acid; the components synergistically work together to significantly reduce plasma prothrombin time and plasma recalcification time, and significantly reduce the whole blood viscosity, plasma viscosity, and hematocrit of rats with blood stasis syndrome. The traditional Chinese medicine composition of the present invention is used in the preparation of drugs for menstrual disorders or menstrual bleeding and metrorrhagia, and has a significant therapeutic effect on irregular menstruation, excessive menstrual bleeding, or metrorrhagia.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for clearing away heat, removing blood stasis, stopping bleeding and regulating menstruation, and a preparation method thereof. Background Art

[0002] Menstrual disorders, also known as irregular menstruation, are common gynecological conditions. Symptoms primarily include early or late menstruation, abnormal bleeding volume, or abdominal pain and systemic symptoms before and during menstruation. For those experiencing prolonged periods, their periods are prolonged, lasting more than seven days or even lasting two weeks. Those with inflammation often experience lower abdominal pain, which worsens during menstruation. They also experience heavy vaginal discharge that is yellow or yellowish-white, thick, and has a strong odor. Those with incomplete corpus luteum atrophy also experience heavy menstrual flow. Those with prolonged endometrial repair may experience a small amount of persistent vaginal bleeding after their normal menstrual period. For those with heavy bleeding, blood loss during a menstrual cycle can exceed 80 mL, and in some cases, exceed 200 mL. Menstrual disorders seriously impact health.

[0003] Modern medicine points out that drugs for treating excessive menstrual bleeding include hormonal and non-hormonal drugs (for example, inhibitors of prostaglandin synthesis, antifibrinolytics and hemostatics). Commonly used hemostatic drugs in obstetrics include oxytocin, ergot alkaloids, prostaglandins, tranexamic acid, etc.

[0004] Traditional Chinese Medicine believes that menorrhagia is caused by blood heat disturbing the Chong and Ren meridians, leading to a restless blood sea, or by Qi deficiency, which is unable to control or retain the blood, leading to a loss of firmness in the Chong and Ren meridians. Excessive menstruation is caused by Qi deficiency, which is unable to control menstrual blood, or by blood heat, which overwhelms the Chong and Ren meridians, forcing blood to flow unchecked, resulting in abnormal yin blood flow. Both syndromes are caused by blood heat and Qi deficiency, so premature menstruation is often accompanied by menorrhagia. In blood heat syndrome, liver depression transforms into fire, which overwhelms the Chong and Ren meridians, forcing blood to flow unchecked and causing excessive blood flow. Clearing heat, cooling the blood, and soothing the liver and regulating Qi are necessary. In Qi deficiency syndrome, spleen deficiency and weak Qi lead to a loss of control over menstrual blood, resulting in a loss of firmness in the Chong and Ren meridians, leading to menorrhagia. Therefore, treatment of this condition requires strengthening the spleen and replenishing Qi, consolidating the Chong and Ren meridians, clearing heat, activating blood circulation, and removing blood stasis, while replenishing blood and stopping bleeding.

[0005] Numerous studies have been conducted in both modern and ancient Chinese medicine on the treatment of menstrual disorders. For example, Chinese invention patent CN107469031A discloses a Chinese herbal composition for treating premature and menorrhagia. The composition is made from a combination of Gardenia jasminoides, Mentha chinensis, Cortex Moutan, Poria cocos, Rhizoma Zingiberis Preparata, Codonopsis pilosula, Cinnamon bark, Ligusticum chuanxiong, Rhizoma scutellariae, White peony flower, Achyranthes bidentata, Bupleurum chinense, Atractylodes macrocephala, Pollen Typhae, Cyperus rotundus, Ostreae officinalis, Rose flower, and Vaccinium myrtillus in specific weight proportions. This invention addresses premature and heavy menstruation caused by blood heat, liver depression, and spleen deficiency, accompanied by dysmenorrhea. It achieves relief and cure by strengthening the spleen and replenishing qi, clearing heat and cooling blood, regulating qi and relieving depression, and nourishing the liver and kidneys, supplemented by promoting blood circulation and relieving pain, removing blood stasis, and stopping bleeding. The composition boasts significant efficacy.

[0006] There is a significant therapeutic effect on irregular menstruation and heavy bleeding, and the Chinese medicine "Xue Ping Pian" that can effectively promote blood circulation and remove blood stasis, stop bleeding and cool blood is derived from the prescription "Hei Pu Huang San" for treating metrorrhagia in the Song Dynasty of my country's "Su An Yi Yao" and is modified with the symptoms. It has the effects of clearing away heat and removing blood stasis, stopping bleeding and regulating menstruation. Based on this, Chinese invention patent CN102327401A provides a preparation method for a pharmaceutical composition for treating metrorrhagia based on Xue Ping Pian. The Xue Ping Pian of the method is made of Rehmannia glutinosa, Rhubarb, Radix Sanguisorbae, Radix Notoginseng, Cuttlebone, Rubia cordifolia and Pollen Typhae (fried) as raw materials, and is mixed, granulated, tabletted and film-coated by modern extraction and separation technologies such as ultrafine grinding, supercritical fluid extraction, ultrasonic extraction, microporous membrane filtration, water extraction and alcohol precipitation. The extraction and separation efficiency of the method is good, and the extraction rate is high, which avoids the degradation of heat-sensitive components and greatly retains the active ingredients. However, the invention does not provide the effects of the prepared traditional Chinese medicine product on promoting blood circulation and removing blood stasis, stopping bleeding, relieving pain, and the uterus, and retaining the active ingredients as much as possible does not necessarily have a significant effect in treating menstrual disorders.

[0007] In recent years, extensive research has been conducted both domestically and internationally on the chemical composition, pharmacological effects, preparation methods, and applications of traditional Chinese medicine (TCM). Active ingredients have become a key avenue for new drug development. Developing a TCM composition with significant heat-clearing, blood-stasis-removing, hemostatic, and menstrual-regulating effects, based on traditional TCM formulas, is of great significance to TCM. Summary of the Invention

[0008] In view of the problems existing in the prior art, the present invention provides a traditional Chinese medicine composition for clearing away heat, removing blood stasis, stopping bleeding and regulating menstruation and a preparation method thereof.

[0009] To achieve the above object, the technical solution adopted by the present invention is as follows:

[0010] First, the present invention provides a traditional Chinese medicine composition for clearing away heat, removing blood stasis, stopping bleeding and regulating menstruation, comprising the following components: catalpol, aucubin, β-sitosterol, emodin, chrysophanol, sanguisorba officinalis extract, notoginseng total saponins, heptacan, cuttlefish shell, rubiacin, typhalaenoside and p-coumaric acid.

[0011] Preferably, the traditional Chinese medicine composition comprises the following components in parts by weight: 0.5-2 parts of catalpol, 1-2.3 parts of aucubin, 2-4.6 parts of β-sitosterol, 1-3.5 parts of emodin, 2-6 parts of chrysophanol, 5-10 parts of sanguisorba officinalis extract, 2-5 parts of notoginseng total saponins, 1-2.5 parts of tris-heptacid, 80-225 parts of cuttlefish shells, 1.1-3 parts of rubiacin, 2-4.8 parts of typhanosides and 1-5.5 parts of p-coumaric acid.

[0012] Further preferably, the traditional Chinese medicine composition comprises the following components, in parts by weight: 0.8-1.5 parts of catalpol, 1.5-2 parts of aucubin, 3-4.3 parts of β-sitosterol, 1.2-2.6 parts of emodin, 3-4 parts of chrysophanol, 6-8 parts of sanguisorba officinalis extract, 3-4.5 parts of notoginseng total saponins, 1.2-2.2 parts of triseptamine, 120-180 parts of cuttlefish shell, 1.5-2.9 parts of rubiacin, 3-4.5 parts of typhanosides and 2.5-4.3 parts of p-coumaric acid.

[0013] Still more preferably, the Chinese medicine composition comprises the following components, in parts by weight: 1.2 parts of catalpol, 1.9 parts of aucubin, 4 parts of β-sitosterol, 2.3 parts of emodin, 3.5 parts of chrysophanol, 7 parts of sanguisorba officinalis extract, 4 parts of notoginseng total saponins, 2 parts of trissepamine, 150 parts of cuttlefish shells, 2.6 parts of rubiacin, 4.1 parts of typhanosides and 3.8 parts of p-coumaric acid.

[0014] Preferably, the preparation method of the Sanguisorba officinalis extract comprises the steps of:

[0015] S1. Mixing the Sanguisorba officinalis solution with an organic solvent, ultrasonically treating the mixture, and then performing reflux extraction to obtain an extract and a Sanguisorba officinalis residue;

[0016] S2, decompressing the extract obtained in step S1 to remove the organic solvent to obtain an active ingredient extract;

[0017] S3, mixing the Sanguisorba officinalis residue obtained in step S1 with water and boiling the mixture to obtain a decoction;

[0018] S4. The active ingredient extract obtained in step S2 and the decoction obtained in step S3 are mixed, concentrated, and dried to obtain a Sanguisorba officinalis extract.

[0019] Further preferably, in step S1, the organic solvent is selected from at least one of ethanol, acetone, and ethyl acetate.

[0020] More preferably, the organic solvent is selected from at least one of ethanol and acetone.

[0021] Further preferably, in step S1, the volume concentration of the organic solvent solution is 30-70%; and the volume concentration is further preferably 40-60%.

[0022] Further preferably, in step S1, the organic solvent solution is an acid-containing organic solvent solution; the acid is selected from at least one of citric acid, succinic acid, malic acid, tartaric acid, acetic acid, and food-grade hydrochloric acid.

[0023] More preferably, the organic solvent solution is an organic solvent solution containing 0.3-1% acid; the acid is selected from at least one of citric acid, succinic acid, malic acid, and tartaric acid.

[0024] Further preferably, in step S1, the Sanguisorba officinalis is mixed with a solution of an organic solvent, and the mixed solid-liquid ratio is 1:20-40 g:mL.

[0025] More preferably, the solid-liquid ratio of the mixture is 1:25-35 g:mL.

[0026] Further preferably, in step S1, the ultrasonic treatment is specifically: using an ultrasonic crusher, the treatment power is 200-400W, the treatment frequency is 40-80kHz, the treatment time is 15-30min, and the treatment temperature is 40-60°C.

[0027] More preferably, the ultrasonic treatment is specifically carried out by using an ultrasonic crusher with a treatment power of 230-350 W, a treatment frequency of 50-60 kHz, a treatment time of 20-25 min, and a treatment temperature of 45-55°C.

[0028] Further preferably, in step S1, the temperature of the reflux extraction is 40-70°C, the time of the reflux extraction is 60-120 min, and after the reflux extraction is completed, the extraction is performed while hot to obtain the extract and the Sanguisorba officinalis residue.

[0029] More preferably, the temperature of the reflux extraction is 45-65° C., the time of the reflux extraction is 80-100 min, and after the reflux extraction is completed, filtration is performed at 40-60° C. while hot to obtain the extract and Sanguisorba officinalis residue.

[0030] Further preferably, in step S2, the decompression can be performed in multiple steps until the organic solvent in the extract is removed; the decompression temperature is 30-60°C.

[0031] Further preferably, in step S3, the decoction is specifically: decoct on low heat for 2-3 times, the solid-liquid ratio of each decoction is 1:10-20g:mL, the decoction time is 0.5-3h, and after each decoction, filtering is performed and the filtrate is combined to obtain a decoction liquid.

[0032] More preferably, the decoction is specifically as follows: decoct twice on low heat, with the solid-liquid ratio of each decoction being 1:12-16 g:mL; the first decoction time is 0.5-1 h, and the filter residue after filtration is further decocted for a second time, with the second decoction time being 2-3 h; and the two filtrates are combined to obtain a decoction liquid.

[0033] Further preferably, in step S4, the concentration is first concentrated under reduced pressure to remove the residual organic solvent, and then dried at a temperature below 60° C. to obtain the Sanguisorba officinalis extract.

[0034] Preferably, the weight ratio of emodin to chrysophanol is 1-3.5:2-6; the weight ratio is more preferably 1.2-2.6:3-4; and the weight ratio is most preferably 2.3:3.5.

[0035] Preferably, the weight ratio of triseptamphenic acid, cuttlefish shell and rubiacin is 1-2.5:80-225:1.1-3; the weight ratio is more preferably 1.2-2.2:120-180:1.5-2.9; the weight ratio is most preferably 2:150:2.6.

[0036] Then, the present invention provides a method for preparing the above-mentioned Chinese medicine composition, comprising the steps of:

[0037] (1) crushing the cuttlefish to obtain cuttlefish powder;

[0038] (2) Mixing the cuttlefish sheath powder with the remaining components in the traditional Chinese medicine composition to obtain the traditional Chinese medicine composition.

[0039] Preferably, in step (1), the pulverization is performed by using a high-speed grinder to produce a fine powder, and the particle size of the cuttlefish sheath powder is 600-800 mesh.

[0040] Furthermore, the present invention provides the use of the above-mentioned traditional Chinese medicine composition in the preparation of a medicine for treating menstrual disorders or menstrual bleeding and metrorrhagia.

[0041] Finally, the present invention provides a medicine for treating menstrual disorders or metrorrhagia, comprising the above-mentioned traditional Chinese medicine composition and / or medically acceptable excipients.

[0042] Preferably, the dosage form of the drug is any pharmaceutically acceptable dosage form, such as tablets, capsules, granules, ointments, patches, mixtures, syrups, pills, injections and sprays.

[0043] More preferably, the dosage form of the drug is any one of tablets, capsules, granules and pills.

[0044] Preferably, the medically acceptable excipients include starch, dextrin, sucrose, milk powder, sweeteners, mannitol, lactose, cellulose and its derivatives, calcium carbonate, cyclodextrin, β-cyclodextrin, phospholipid materials, magnesium stearate, talc or flavors.

[0045] In the present invention, catalpol and aucubin are the main active ingredients of the traditional Chinese medicine Rehmannia glutinosa; catalpol has the effects of clearing heat and cooling blood, nourishing yin and promoting body fluid; it can also play a good laxative effect and relieve pain; aucubin has the effects of clearing heat and detoxifying, reducing swelling and stopping bleeding, and promoting blood circulation and relieving pain (analgesia).

[0046] In the present invention, the β-sitosterol is widely present in traditional Chinese medicines such as Rehmannia glutinosa and Pollen Typhae, and has the effect of promoting wound healing and repairing tissues.

[0047] In the present invention, the emodin and chrysophanol are the main active ingredients in cooked rhubarb. Emodin can promote blood coagulation and platelet aggregation, thereby improving the situation of continuous bleeding and achieving a hemostatic effect.

[0048] In the present invention, the Sanguisorba officinalis extract contains a large amount of tannin components, such as catechins, gallic acid, quercetin, ursolic acid, Sanguisorba officinalis saponins and other components. Specific extraction work is performed on the Sanguisorba officinalis, and the obtained Sanguisorba officinalis extract works synergistically with components such as cuttlefish sheath and emodin, and has significant effects such as clearing heat and stopping bleeding.

[0049] In the present invention, the Panax notoginseng total saponins are effective ingredients extracted from the traditional Chinese medicine Panax notoginseng. Panax notoginseng total saponins have the effects of promoting blood circulation, removing blood stasis, dredge meridians and activate collaterals, inhibit platelet aggregation, etc.; they can clear blood heat, cool blood and stop bleeding, and are good at promoting blood circulation, removing blood stasis and dredge menstruation, and can shorten bleeding and clotting time.

[0050] In the present invention, the cuttlebone astringent and firming properties work together with hepta-septamine and rubiacin to enhance hemostatic efficacy. The combination of the various Chinese medicinal herbs and their active ingredients allows the formula to stop bleeding without leaving stasis, dissipate heat without damaging yin, remove stasis, clear heat, and regulate blood circulation and menstruation.

[0051] In the present invention, the typhalaenoside and p-coumaric acid are the main active ingredients in Pollen Typhae, which is sweet and neutral in nature. It enters the liver and pericardium meridians and has the effects of stopping bleeding, removing blood stasis, and relieving stranguria. It is used to treat hematemesis, epistaxis, hemoptysis, metrorrhagia, traumatic bleeding, amenorrhea, dysmenorrhea, stabbing pain in the chest and abdomen, swelling and pain caused by falls, and painful stranguria caused by blood.

[0052] Compared with the prior art, the present invention has the following beneficial effects:

[0053] 1. The present invention screens and coordinates the Chinese medicinal ingredients and active ingredients to obtain a Chinese medicinal composition containing catalpol aucubin, β-sitosterol, emodin, chrysophanol, sanguisorba officinalis extract, notoginseng total saponins, heptaglutine, cuttlefish sheath, rubiacin, typhalaenoside and p-coumaric acid. The active ingredients cooperate with each other to significantly reduce plasma prothrombin time and plasma recalcification time. The Chinese medicinal composition of the present invention has the effect of significantly reducing the whole blood specific viscosity, plasma viscosity and hematocrit of blood stasis syndrome model rats through reasonable matching between components and efficient preparation method. It is applied to the preparation of drugs for menstrual disorders or menstrual bleeding and metrorrhagia, and has a significant therapeutic effect on irregular menstruation, excessive menstrual bleeding or metrorrhagia.

[0054] 2. The present invention comprehensively utilizes active ingredients, and the Chinese medicine composition has clear ingredients and reasonable combinations, which is beneficial to absorption and effectively exerts the effects of each active ingredient. The present invention obtains active ingredients by coordinating specific active ingredients with each other and by a specific extraction method. The prepared Chinese medicine composition has high activity and a high utilization rate of active ingredients, and can effectively treat irregular menstruation and symptoms such as distension and pain during menstruation, bluish complexion, long-term and irregular menstruation, etc. DETAILED DESCRIPTION

[0055] The following non-limiting examples are provided to enable those skilled in the art to more fully understand the present invention, but are not intended to limit the present invention in any way. The following are merely illustrative of the scope of the present invention, and those skilled in the art may make various changes and modifications to the present invention based on the disclosed content, which should also fall within the scope of the present invention.

[0056] When numerical ranges are given in the examples, it should be understood that, unless otherwise specified herein, both endpoints of each numerical range and any value between the two endpoints may be selected. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which the invention belongs.

[0057] The present invention is further described below in the form of specific examples. Unless otherwise specified, the various chemical reagents and components used in the examples of the present invention are obtained through conventional commercial channels. Products from different manufacturers do not have a significant effect on the effect. Catalpol, CAS No. 2415-24-9; Aucubin, CAS No. 479-98-1; β-sitosterol, CAS No. 83-46-5; Emodin, CAS No. 518-82-1; Chrysophanol, CAS No. 481-74-3; Panax notoginseng total saponins, CAS No. 88105-29-7; Trisepeptide, CAS No. 7554-90-7; Rubiatin, CAS No. 72-48-0; Typhanoside, CAS No. 104472-68-6; p-Coumaric acid, CAS No. 7400-08-0.

[0058] Example 1

[0059] A traditional Chinese medicine composition for clearing away heat, removing blood stasis, stopping bleeding and regulating menstruation comprises the following components, measured by weight: 1.2 parts of catalpol, 1.9 parts of aucubin, 4 parts of β-sitosterol, 2.3 parts of emodin, 3.5 parts of chrysophanol, 7 parts of sanguisorba officinalis extract, 4 parts of notoginseng total saponins, 2 parts of trissepamine, 150 parts of cuttlefish shells, 2.6 parts of rubiacin, 4.1 parts of typhanosides and 3.8 parts of p-coumaric acid.

[0060] The preparation method of the Sanguisorba officinalis extract comprises the steps of:

[0061] S1. Mixing the Sanguisorba officinalis with a 56% ethanol solution at a solid-liquid ratio of 1:30 g:mL, wherein the ethanol solution also contains 0.4% citric acid; after mixing, ultrasonic treatment is performed: using an ultrasonic crusher, the ultrasonic treatment power is 300 W, the frequency is 55 kHz, the treatment time is 22 min, and the temperature is 50°C; after ultrasonic treatment, reflux extraction is performed at 55°C for 90 min. After the reflux extraction is completed, the extract is filtered while hot at about 50°C to obtain an extract and a Sanguisorba officinalis residue;

[0062] S2, concentrating the extract obtained in step S1 under reduced pressure to remove the organic solvent to obtain an active ingredient extract;

[0063] S3, the Sanguisorba officinalis residue of step S1 was mixed with 15 times the amount of water and decocted on low heat twice, the solid-liquid ratio of each decoction was 1:15g:mL, the first decoction time was 1h, and the filter residue was filtered and continued to be decocted twice, the second decoction time was 2h; the two filtrates were combined to obtain a decoction;

[0064] S4. The active ingredient extract obtained in step S2 and the decoction obtained in step S3 are mixed, concentrated under reduced pressure, the residual organic solvent is removed, and then dried at a temperature below 60° C. to obtain the Sanguisorba officinalis extract.

[0065] The preparation method of the traditional Chinese medicine composition comprises the steps of:

[0066] (1) using a high-speed grinder to grind the cuttlefish sheath into a fine powder to obtain a cuttlefish sheath powder having a particle size of about 700 meshes;

[0067] (2) Mixing the cuttlefish sheath powder with the remaining components in the traditional Chinese medicine composition to obtain the traditional Chinese medicine composition.

[0068] Example 2

[0069] A traditional Chinese medicine composition for clearing away heat, removing blood stasis, stopping bleeding and regulating menstruation comprises the following components in parts by weight: 0.8 parts of catalpol, 1.5 parts of aucubin, 3 parts of β-sitosterol, 1.2 parts of emodin, 3 parts of chrysophanol, 6 parts of sanguisorba officinalis extract, 3 parts of notoginseng total saponins, 1.2 parts of trissepamine, 120 parts of cuttlefish shells, 1.5 parts of rubiacin, 3 parts of typhanenoside and 2.5 parts of p-coumaric acid.

[0070] The preparation methods of the Sanguisorba officinalis extract and the preparation methods of the Chinese medicine composition are the same as those in Example 1.

[0071] Example 3

[0072] A traditional Chinese medicine composition for clearing away heat, removing blood stasis, stopping bleeding and regulating menstruation comprises the following components in parts by weight: 1.5 parts of catalpol, 2 parts of aucubin, 4.3 parts of β-sitosterol, 2.6 parts of emodin, 4 parts of chrysophanol, 8 parts of sanguisorba officinalis extract, 4.5 parts of notoginseng total saponins, 2.2 parts of trissepamine, 180 parts of cuttlefish shells, 2.9 parts of rubiacin, 4.5 parts of typhanosides and 4.3 parts of p-coumaric acid.

[0073] The preparation method of the Sanguisorba officinalis extract comprises the steps of:

[0074] S1. Mixing the Sanguisorba officinalis with a 60% ethanol solution at a solid-liquid ratio of 1:35 g:mL, wherein the ethanol solution also contains 0.5% citric acid; after mixing, ultrasonic treatment is performed: using an ultrasonic crusher, the ultrasonic treatment power is 350 W, the frequency is 60 kHz, the treatment time is 25 min, and the temperature is 55°C; after ultrasonic treatment, reflux extraction is performed at 65°C for 100 min. After the reflux extraction is completed, the extract is filtered at about 60°C while hot to obtain an extract and a Sanguisorba officinalis residue;

[0075] S2, concentrating the extract obtained in step S1 under reduced pressure to remove the organic solvent to obtain an active ingredient extract;

[0076] S3, the Sanguisorba officinalis residue of step S1 was mixed with 16 times the amount of water and decocted on low heat twice, the solid-liquid ratio of each decoction was 1:16g:mL, the first decoction time was 0.5h, and the filter residue was filtered and then decocted twice, the second decoction time was 3h; the two filtrates were combined to obtain a decoction;

[0077] S4. The active ingredient extract obtained in step S2 and the decoction obtained in step S3 are mixed, concentrated under reduced pressure, the residual organic solvent is removed, and then dried at a temperature below 60° C. to obtain the Sanguisorba officinalis extract.

[0078] The preparation method of the Chinese medicine composition is the same as that in Example 1.

[0079] Example 4

[0080] A traditional Chinese medicine composition for clearing away heat, removing blood stasis, stopping bleeding and regulating menstruation, comprising the following components by weight: 0.5 parts of catalpol, 1 part of aucubin, 2 parts of β-sitosterol, 1 part of emodin, 2 parts of chrysophanol, 5 parts of sanguisorba officinalis extract, 2 parts of total saponins of Panax notoginseng, 1 part of

[0081] Triheptaminic acid, 80 parts of cuttlefish shell, 1.1 parts of rubiacin, 2 parts of typhanoside and 1 part of p-coumaric acid.

[0082] The preparation method of the Sanguisorba officinalis extract comprises the steps of:

[0083] S1. Mixing Sanguisorba officinalis with a 70% ethanol solution at a solid-liquid ratio of 1:35 g:mL, wherein the ethanol solution also contains 0.6% tartaric acid; after mixing, ultrasonic treatment is performed: using an ultrasonic crusher, the ultrasonic treatment power is 400 W, the frequency is 80 kHz, the treatment time is 30 min, and the temperature is 60°C; after ultrasonic treatment, reflux extraction is performed at 70°C for 120 min. After the reflux extraction is completed, the extract is filtered while hot at about 60°C to obtain an extract and Sanguisorba officinalis residue;

[0084] S2, concentrating the extract obtained in step S1 under reduced pressure to remove the organic solvent to obtain an active ingredient extract;

[0085] S3, the Sanguisorba officinalis residue of step S1 was mixed with 20 times the amount of water and decocted on low heat three times, the solid-liquid ratio of each decoction was 1:20g:mL, the decoction time was 1h, and the residue after filtering was continued to be decocted for the next time; filtered, and the filtrate was combined three times to obtain a decoction;

[0086] S4. The active ingredient extract obtained in step S2 and the decoction obtained in step S3 are mixed, concentrated under reduced pressure, the residual organic solvent is removed, and then dried at a temperature below 60° C. to obtain the Sanguisorba officinalis extract.

[0087] The preparation method of the Chinese medicine composition is the same as that in Example 1.

[0088] Example 5

[0089] A traditional Chinese medicine composition for clearing away heat, removing blood stasis, stopping bleeding and regulating menstruation comprises the following components, measured by weight: 2 parts of catalpol, 2.3 parts of aucubin, 4.6 parts of β-sitosterol, 3.5 parts of emodin, 6 parts of chrysophanol, 10 parts of sanguisorba officinalis extract, 5 parts of notoginseng total saponins, 2.5 parts of trissepamine, 225 parts of cuttlefish shells, 3 parts of rubiacin, 4.8 parts of typhanosides and 5.5 parts of p-coumaric acid.

[0090] The preparation method of the Sanguisorba officinalis extract comprises the steps of:

[0091] S1. Mixing the Sanguisorba officinalis with a 70% volume concentration of acetone solution at a solid-liquid ratio of 1:25 g:mL, wherein the ethanol solution also contains 0.5% tartaric acid; after mixing, ultrasonic treatment is performed: using an ultrasonic crusher, the ultrasonic treatment power is 230 W, the frequency is 50 kHz, the treatment time is 30 min, and the temperature is 45°C; after ultrasonic treatment, reflux extraction is performed at 70°C for 120 min. After the reflux extraction is completed, the extract is filtered at about 60°C while hot to obtain an extract and a Sanguisorba officinalis residue;

[0092] S2, concentrating the extract obtained in step S1 under reduced pressure to remove the organic solvent to obtain an active ingredient extract;

[0093] S3, the Sanguisorba officinalis residue of step S1 was mixed with 12 times the amount of water and decocted on low heat three times, the solid-liquid ratio of each decoction was 1:12g:mL, and the decoction time was 1.5h. After filtering, the residue was continued to be decocted for the next time; filtered, and the filtrate was combined three times to obtain a decoction;

[0094] S4. The active ingredient extract obtained in step S2 and the decoction obtained in step S3 are mixed, concentrated under reduced pressure, the residual organic solvent is removed, and then dried at a temperature below 60° C. to obtain the Sanguisorba officinalis extract.

[0095] The preparation method of the traditional Chinese medicine composition comprises the steps of:

[0096] (1) using a high-speed grinder to grind the cuttlefish sheath into a fine powder to obtain a cuttlefish sheath powder having a particle size of about 800 meshes;

[0097] (2) Mixing the cuttlefish sheath powder with the remaining components in the traditional Chinese medicine composition to obtain the traditional Chinese medicine composition.

[0098] Comparative Example 1

[0099] The difference from Example 1 is that the components of the traditional Chinese medicine composition are different, and the traditional Chinese medicine composition does not contain the component β-sitosterol.

[0100] The rest are the same as in Example 1.

[0101] Comparative Example 2

[0102] The difference from Example 1 is that the components of the traditional Chinese medicine composition are different, and the traditional Chinese medicine composition does not contain the component Rubiacin.

[0103] The rest are the same as in Example 1.

[0104] Comparative Example 3

[0105] Different from Example 1, the components of the traditional Chinese medicine composition are different, and aucubin is replaced by rehmannia glutinose.

[0106] The rest are the same as in Example 1.

[0107] Comparative Example 4

[0108] The difference from Example 1 is that the components of the traditional Chinese medicine composition are different, and p-coumaric acid is replaced by gallic acid.

[0109] The rest are the same as in Example 1.

[0110] Comparative Example 5

[0111] The difference from Example 1 is that the weight ratio of emodin and chrysophanol is different, specifically: in parts by weight, the components include: 1.2 parts of catalpol, 1.9 parts of aucubin, 4 parts of β-sitosterol, 5 parts of emodin, 0.5 part of chrysophanol, 7 parts of Sanguisorba officinalis extract, 4 parts of Panax notoginseng total saponins, 2 parts of trissepamine, 150 parts of sea cucumber, 2.6 parts of madder, 4.1 parts of typhanosides and 3.8 parts of p-coumaric acid.

[0112] The rest are the same as in Example 1.

[0113] Comparative Example 6

[0114] Different from Example 1, the weight ratio of heptanoic acid, cuttlefish shell and madder is different, specifically: in parts by weight, including components: 1.2 parts of catalpol, 1.9 parts of aucubin, 4 parts of β-sitosterol, 2.3 parts of emodin, 3.5 parts of chrysophanol, 7 parts of Sanguisorba officinalis extract, 4 parts of Panax notoginseng total saponins, 3 parts of heptanoic acid, 60 parts of cuttlefish shell, 0.6 part of madder, 4.1 parts of typhanoside and 3.8 parts of p-coumaric acid.

[0115] Comparative Example 7

[0116] The difference from Example 1 is that the preparation method of the Sanguisorba officinalis extract is different, specifically, no organic solvent is used, and the extract is directly treated with water, comprising the steps of:

[0117] S1. Mixing sanguisorba officinalis water with a solid-liquid ratio of 1:30 g:mL, and containing 0.4% citric acid in the water; after mixing, ultrasonic treatment was performed using an ultrasonic crusher with an ultrasonic treatment power of 300 W, a frequency of 55 kHz, a treatment time of 22 min, and a temperature of 50°C; after ultrasonic treatment, decocting the mixture over low heat twice, each decoction having a solid-liquid ratio of 1:15 g:mL, and the first decoction time being 1 h. After filtering, the residue was further decocted for a second time, and the second decoction time was 2 h; combining the two filtrates to obtain a decoction;

[0118] S2. Concentrating under reduced pressure and drying at a temperature below 60° C. to obtain a Sanguisorba officinalis extract.

[0119] The formula, proportion and preparation method of the Chinese medicine composition are the same as those in Example 1.

[0120] Comparative Example 8

[0121] The difference from Example 1 is that the components of the traditional Chinese medicine composition are different, and 150 parts of cuttlefish sheaths are replaced by 150 parts of catechu.

[0122] The method for preparing a Chinese medicine composition comprises the steps of:

[0123] (1) using a high-speed grinder to grind catechu into fine powder to obtain catechu powder with a particle size of about 700 mesh;

[0124] (2) Mixing the catechu powder with the remaining components of the traditional Chinese medicine composition to obtain the traditional Chinese medicine composition.

[0125] Comparative experiment 1 Effect of Chinese herbal medicine composition on rabbit plasma prothrombin time and plasma recalcification time

[0126] Animals: Adult female New Zealand white rabbits (Jiangxi Laibu Biotechnology Co., Ltd.), weighing 3.8-4 kg, were divided into 17 groups, with 6 rabbits in each group. Before the experiment, the rabbits were fed adaptively for 1 week.

[0127] Blank control group: gavage with drinking water;

[0128] Positive control group: intragastric blood tablets, purchased from Jiangxi Puzheng Pharmaceutical Co., Ltd.;

[0129] Experimental groups: 15 groups in total, including the low-dose group of Example 1, the medium-dose group of Example 1, the high-dose group of Example 1, the medium-dose group of Examples 2-5, a total of 4 groups, and the medium-dose groups of Comparative Examples 1-8, a total of 8 groups. The dose of the low-dose group was 20 mg / kg, the dose of the medium-dose group was 40 mg / kg, and the dose of the high-dose group was 80 mg / kg.

[0130] After adaptive feeding, the rabbits were gavaged for three consecutive days with the Chinese medicine compositions of different Examples and Comparative Examples. Blood was drawn one hour after administration on the third day. Plasma prothrombin time and plasma recalcification time were measured.

[0131] Plasma prothrombin time (PT) testing: Draw 1.8 ml of venous blood and slowly inject it into a plastic test tube containing 0.2 ml of 109 mmol / L sodium citrate solution. Mix thoroughly, centrifuge at 3000 rpm for 15 minutes, remove platelets, and separate the plasma. Add 0.1 ml of the test plasma to another plastic test tube and preheat in a 37°C water bath for 3 minutes. Add 0.1 ml of PT reagent preheated to 37°C and immediately start the timer. Tilt the test tube repeatedly in the water bath to mix, slowly tilting the tube. The endpoint of the PT is calculated based on the appearance of turbidity at the beginning of coagulation. Repeat the test twice and calculate the average of the two times. The final test results are shown in Table 1.

[0132] Plasma recalcification time was measured by placing 0.1 ml of plasma into a clean glass test tube with an inner diameter of 10 mm. The tube was kept in a 37°C water bath for 2 minutes. 0.1 ml of a sample solution of a certain concentration was added to the test tube, shaken, and kept in a constant temperature for 2 minutes. Then, 0.1 ml of a 0.775% CaCl₂ solution was added. The time was immediately measured, with the test tube tilted every 10 seconds until the liquid level remained still. This was the plasma recalcification time. Repeat this experiment twice. The final test results are shown in Table 1.

[0133] Table 1

[0134]

[0135] In Table 1, compared with the blank control group: *P<0.05, **P<0.01.

[0136] As can be seen from Table 1, the Chinese medicine composition described in the present application can significantly reduce plasma prothrombin time and plasma recalcification time, and the effect is better than that of Xueping tablets.

[0137] Comparative experiment 2: The therapeutic effect of the Chinese herbal medicine combination on rats with "blood stasis" syndrome

[0138] Animals: Adult female SD rats, 12-14 weeks old, weighing 220-250g, were divided into 17 groups, with 6 rats per group. Grouping was similar to that in Comparative Study 1, resulting in 18 groups: a blank control group, a model control group, a positive control group, and 15 experimental groups. The low-dose group received 20 mg / kg, the medium-dose group received 40 mg / kg, and the high-dose group received 80 mg / kg. Adaptive feeding was performed for 1 week prior to the experiment.

[0139] To establish the model, all rats, except for the blank control group, were treated with epinephrine and ice water stimulation using conventional methods for establishing blood stasis syndrome. Successful modeling was indicated by significant increases in whole blood viscosity, plasma viscosity, and hematocrit. All rats exhibited significant increases in these values, confirming successful modeling.

[0140] The rats in different groups were treated with oral gavage for 3 days. One hour after oral gavage on the third day, the whole blood viscosity, plasma viscosity and hematocrit were tested. The test results are shown in Table 2.

[0141] Table 2

[0142]

[0143]

[0144] In Table 2, compared with the blank control group: *P < 0.05, **P < 0.01; compared with the model group, ΔP < 0.05, ΔΔP < 0.01.

[0145] As can be seen from Table 2, the Chinese medicine composition described in this application can significantly reduce whole blood specific viscosity, plasma viscosity, and hematocrit. The medium and high doses of the Chinese medicine composition of this application have the best effect, and the effect is better than the model group and the blood level tablets.

[0146] Comparative trial 3 clinical application

[0147] Case 1: Ms. Li, 40 years old, suffered from irregular menstruation, metrorrhagia, and menstrual bleeding that lasted for 10 days for 4 months. After taking the medicine prepared by the pharmaceutical composition of Example 1 of the present invention for 2 courses of treatment, her symptoms were alleviated, her menstrual period became regular, her menstrual bleeding became normal, and her menstrual period stopped within 7 days.

[0148] Case 2: Zhou, female, 33 years old, had early menstruation for one year, with variable amounts of blood and purple-red color. She also had chest and breast pain before menstruation, lower abdominal pain during menstruation, and irregular periods. Her menstruation was frequent in the latter stages. Her complexion was faintly blue, with veins visible between her cheeks and nose, dark lips, and dark circles around her eyes. After two courses of treatment with the drug prepared from the pharmaceutical composition of Example 1 of the present invention, her symptoms were significantly alleviated. After three months of treatment, her menstrual periods became regular, bleeding volume was normal, and the pain and distension were alleviated. One year of follow-up showed that her menstruation was normal.

[0149] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A Chinese medicine composition for clearing away heat, removing blood stasis, stopping bleeding and regulating menstruation, characterized in that: The invention comprises the following components in parts by weight: 0.5-2 parts of catalpol, 1-2.3 parts of aucubin, 2-4.6 parts of β-sitosterol, 1-3.5 parts of emodin, 2-6 parts of chrysophanol, 5-10 parts of sanguisorba officinalis extract, 2-5 parts of total saponins of Panax notoginseng, 1-2.5 parts of trissepeptide, 80-225 parts of cuttlefish shell, 1.1-3 parts of rubiacin, 2-4.8 parts of typhanoside and 1-5.5 parts of p-coumaric acid; The preparation method of the Sanguisorba officinalis extract comprises the following steps: S1. Mixing Sanguisorba officinalis with a solution of an organic solvent, ultrasonically treating the mixture, and then performing reflux extraction to obtain an extract and Sanguisorba officinalis residue; the organic solvent is selected from at least one of ethanol and acetone; and the volume concentration of the organic solvent solution is 30-70%; The organic solvent solution is an organic solvent solution containing an acid; the acid is selected from at least one of citric acid and tartaric acid; The Sanguisorba officinalis solution is mixed with an organic solvent solution at a solid-liquid ratio of 1:25-35 g:mL; S2, decompressing the extract obtained in step S1 to remove the organic solvent to obtain an active ingredient extract; S3, mixing the Sanguisorba officinalis residue obtained in step S1 with water and boiling the mixture to obtain a decoction; S4. The active ingredient extract obtained in step S2 and the decoction obtained in step S3 are mixed, concentrated, and dried to obtain a Sanguisorba officinalis extract.

2. The Chinese medicine composition according to claim 1, characterized in that The invention is composed of the following components in parts by weight: 0.8-1.5 parts of catalpol, 1.5-2 parts of aucubin, 3-4.3 parts of β-sitosterol, 1.2-2.6 parts of emodin, 3-4 parts of chrysophanol, 6-8 parts of sanguisorba officinalis extract, 3-4.5 parts of total saponins of Panax notoginseng, 1.2-2.2 parts of triseptamine, 120-180 parts of cuttlefish sheath, 1.5-2.9 parts of rubiacin, 3-4.5 parts of typhanoside and 2.5-4.3 parts of p-coumaric acid.

3. The Chinese medicine composition according to claim 1, characterized in that In step S1, the ultrasonic treatment is specifically: using an ultrasonic crusher, the treatment power is 200-400W, the treatment frequency is 40-80kHz, the treatment time is 15-30min, and the treatment temperature is 40-60°C; The temperature of the reflux extraction is 40-70° C., and the time of the reflux extraction is 60-120 min. After the reflux extraction is completed, the extraction is performed while hot to obtain an extract and Sanguisorba officinalis residue.

4. The Chinese medicine composition according to claim 1, characterized in that In step S2, the decompression temperature is 30-60°C; In step S3, the decoction is specifically: decoct on low heat 2-3 times, the solid-liquid ratio of each decoction is 1:10-20g:mL, the decoction time is 0.5-3h, and after each decoction, filtering is performed and the filtrate is combined to obtain a decoction liquid; in step S4, the drying is performed at a temperature below 60°C to obtain the Sanguisorba officinalis extract.

5. The Chinese medicine composition according to any one of claims 1 to 2, characterized in that The weight ratio of emodin to chrysophanol is 2.3:3.5; the weight ratio of triheptanoic acid, cuttlefish shell and madder is 2:150:2.

6.

6. The method for preparing the Chinese medicine composition according to any one of claims 1 to 5, characterized in that: Including steps: (1) crushing the cuttlefish sheath to obtain cuttlefish sheath powder; (2) Mixing the cuttlefish sheath powder with the remaining components of the traditional Chinese medicine composition to obtain the traditional Chinese medicine composition.

7. Use of the Chinese medicine composition according to any one of claims 1 to 5 in the preparation of a medicament for treating menstrual disorders or menstrual bleeding and metrorrhagia.

8. A medicine for treating menstrual disorders or metrorrhagia, characterized in that: The invention comprises a traditional Chinese medicine composition and / or medically acceptable excipients; the traditional Chinese medicine composition is the traditional Chinese medicine composition according to any one of claims 1 to 5 or the traditional Chinese medicine composition prepared by the preparation method according to claim 6.

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