A compound preparation of Lithospermum erythrorhizon traditional Chinese medicine, its preparation method and application

Abstract

The present invention relates to a compound preparation of Chinese herbal medicine of Lithospermum erythrorhizon, its preparation method and application, and belongs to the technical field of Chinese herbal medicine. The compound preparation of Chinese herbal medicine of Lithospermum erythrorhizon includes a Chinese herbal medicine composition and pharmaceutical excipients. Calculated by weight parts, the Chinese herbal medicine composition comprises the following raw materials: 55-75 parts of Lithospermum erythrorhizon, 10-20 parts of Poria cocos, and 25-40 parts of Rabdosia lophanthoides var. gerardiana. The compound preparation of Chinese herbal medicine of Lithospermum erythrorhizon provided by the present invention uses a Chinese herbal medicine composition mainly composed of Lithospermum erythrorhizon and compounded with appropriate amounts of Poria cocos and Rabdosia lophanthoides var. gerardiana as the active ingredient, and the three complement each other and have synergistic effects. The results of animal experiments show that the Chinese herbal medicine composition can effectively inhibit the increase in heart weight of a myocardial hypertrophy mouse model and significantly reduce its serum LDH level, which not only provides a new means for the clinical treatment of hypertrophic cardiomyopathy, but also further broadens the application scope of these Chinese medicinal materials in the medical field.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and particularly to a compound preparation of Lithospermum erythrorhizon traditional Chinese medicine, its preparation method and application. Background Art

[0002] Hypertrophic Cardiomyopathy (HCM) is a hereditary cardiomyopathy, and its typical feature is the abnormal thickening of the ventricular wall, which often leads to the narrowing of the ventricular cavity, obstruction of left ventricular filling, and significant reduction of diastolic compliance. The clinical manifestations are exertional dyspnea, chest pain, syncope, and even sudden death in extreme cases, becoming an important cause of sudden death in adolescents and athletes. Currently, there are various treatment methods for hypertrophic cardiomyopathy in clinical practice, including drug treatment, non-drug treatment (such as septal ablation, surgical septal myectomy), and pacing treatment, etc. However, drug treatment is often accompanied by side effects, non-drug treatment has certain risks and traumas, and not all patients are suitable for these treatment methods. Therefore, exploring a safe and effective treatment method has become an urgent problem to be solved clinically.

[0003] The treatment of hypertrophic cardiomyopathy with traditional Chinese medicine has shown its unique advantages. Traditional Chinese medicine, with its multi-component, multi-target, and multi-pathway mechanism of action, can comprehensively regulate the body's functions, improve microcirculation, effectively reduce the burden on the heart, and thus relieve the related symptoms of hypertrophic cardiomyopathy. In addition, traditional Chinese medicine treatment also has many advantages such as small side effects and low drug resistance, providing new ideas for the treatment of hypertrophic cardiomyopathy. Among them, Lithospermum erythrorhizon, Poria cocos, and Rabdosia lophanthoides var. gerardiana are commonly used traditional Chinese medicine materials, each with its unique medicinal effects. Lithospermum erythrorhizon, derived from the dried roots of Lithospermum erythrorhizon Sieb. et Zucc. or Arnebia euchroma (Royle) Johnst. of the Boraginaceae family, has the effects of promoting blood circulation to remove blood stasis, cooling blood and detoxifying, etc. Modern pharmacological studies have further revealed its various pharmacological effects such as anti-inflammatory and antioxidant, providing a scientific basis for the treatment with traditional Chinese medicine. Poria cocos, the dried sclerotium of the fungus Poria cocos (Schw.) Wolf of the Polyporaceae family, with the sclerotium as the medicinal part, has the effects of promoting diuresis to eliminate dampness, strengthening the spleen and calming the heart, etc., and is commonly used to treat edema with oliguria, poor appetite due to spleen deficiency, etc. Rabdosia lophanthoides var. gerardiana, belonging to the Lamiaceae family, the whole herb of which can be used as medicine, has the effects of clearing heat and detoxifying, detumescence and analgesia, etc., and is commonly used in folk to treat traumatic injuries, etc.

[0004] Although Lithospermum erythrorhizon, Poria cocos, and Rabdosia lophanthoides var. gerardiana each have significant pharmacological effects and are widely used in the treatment with traditional Chinese medicine, there is no report in the prior art on the combined application of these three in the treatment of hypertrophic cardiomyopathy. Summary of the Invention

[0005] To solve the above problems, the present invention provides a compound preparation of Lithospermum erythrorhizon traditional Chinese medicine, its preparation method and application.

[0006] In a first aspect, the present invention provides a compound preparation of Chinese herbal medicine of Lithospermum erythrorhizon, and the compound preparation of Chinese herbal medicine of Lithospermum erythrorhizon includes a Chinese herbal medicine composition and pharmaceutical excipients; calculated by weight parts, the Chinese herbal medicine composition includes the following raw materials:

[0007] 55 to 75 parts of Lithospermum erythrorhizon, 10 to 20 parts of Poria cocos, and 25 to 40 parts of Rabdosia lophanthoides (Buch.-Ham.) Hara var. gerardiana (Wall.) Hara.

[0008] Further, calculated by weight parts, the Chinese herbal medicine composition includes the following raw materials:

[0009] 60.5 parts of Lithospermum erythrorhizon, 14 parts of Poria cocos, and 32 parts of Rabdosia lophanthoides (Buch.-Ham.) Hara var. gerardiana (Wall.) Hara.

[0010] Further, calculated by weight parts, the Chinese herbal medicine composition includes the following raw materials:

[0011] 55 parts of Lithospermum erythrorhizon, 10 parts of Poria cocos, and 25 parts of Rabdosia lophanthoides (Buch.-Ham.) Hara var. gerardiana (Wall.) Hara.

[0012] Further, calculated by weight parts, the Chinese herbal medicine composition includes the following raw materials:

[0013] 75 parts of Lithospermum erythrorhizon, 20 parts of Poria cocos, and 40 parts of Rabdosia lophanthoides (Buch.-Ham.) Hara var. gerardiana (Wall.) Hara.

[0014] Further, the dosage form of the compound preparation of Chinese herbal medicine of Lithospermum erythrorhizon includes tablets, capsules, decoctions or granules.

[0015] Further, the pharmaceutical excipients include dextrin and ethanol with a volume percentage of 80 to 90%, and the weight ratio of the Chinese herbal medicine composition, the dextrin and the ethanol is 100:(55 to 65):(9 to 17).

[0016] In a second aspect, the present invention provides a preparation method of the compound preparation of Chinese herbal medicine of Lithospermum erythrorhizon according to any one of the first aspect, and the preparation method of the compound preparation of Chinese herbal medicine of Lithospermum erythrorhizon includes the following steps:

[0017] Mix and pulverize Lithospermum erythrorhizon, Poria cocos and Rabdosia lophanthoides (Buch.-Ham.) Hara var. gerardiana (Wall.) Hara to obtain a mixed material;

[0018] Add the mixed material to water for reduced-pressure reflux extraction, and then concentrate and dry the obtained water extract to obtain the Chinese herbal medicine composition;

[0019] Mix and prepare the Chinese herbal medicine composition and the pharmaceutical excipients into a formed product to obtain the compound preparation of Chinese herbal medicine of Lithospermum erythrorhizon.

[0020] Further, the working condition parameters of the reduced-pressure reflux extraction include: the pressure is 9 to 17 kPa, the temperature is 48 to 60 °C, the time is 60 to 90 minutes, the number of times is 1 to 3 times, and the weight ratio of the mixed material and the water is 1:(8 to 12).

[0021] In a third aspect, the present invention provides the use of the Lithospermum officinale traditional Chinese medicine compound preparation according to any one of the first aspect or the Lithospermum officinale traditional Chinese medicine compound preparation prepared by the preparation method according to any one of the second aspect in the preparation of a medicament for treating hypertrophic cardiomyopathy.

[0022] The above technical solutions provided by the embodiments of the present invention have at least the following advantages compared with the prior art:

[0023] The embodiments of the present invention provide a Lithospermum officinale traditional Chinese medicine compound preparation, its preparation method and application. The Lithospermum officinale traditional Chinese medicine compound preparation provided by the present invention uses a traditional Chinese medicine composition mainly composed of Lithospermum officinale and appropriately compounded with Poria cocos and Rabdosia lophanthoides var. gerardiana as the active ingredient. Lithospermum officinale is used as the main drug, and its promoting blood circulation and removing blood stasis effect can improve the microcirculation of the heart and reduce myocardial ischemia and injury caused by myocardial hypertrophy. Supplementary with the effects of Poria cocos in promoting diuresis and removing dampness, strengthening the spleen and calming the heart, it helps to reduce the burden on the heart and promote the recovery of heart function. And the heat-clearing and detoxifying effect of Rabdosia lophanthoides var. gerardiana can reduce heart inflammation, reduce the damage of inflammatory factors to myocardial cells, and protect myocardial cells. The three complement each other and synergistically enhance the effect. The results of animal experiments show that this traditional Chinese medicine composition can effectively inhibit the increase in heart weight in a mouse model of myocardial hypertrophy and significantly reduce the serum LDH (lactate dehydrogenase) level. It not only provides a new means for the clinical treatment of hypertrophic cardiomyopathy, but also further broadens the application scope of these traditional Chinese medicines in the medical field. Description of the Drawings

[0024] The drawings herein are incorporated into the specification and constitute a part of this specification, showing embodiments consistent with the present invention and used together with the specification to explain the principles of the present invention.

[0025] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for the description of the embodiments or the prior art. Obviously, for those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative efforts.

[0026] Figure 1 It is a schematic flowchart of a preparation method of a Lithospermum officinale traditional Chinese medicine compound preparation provided by an embodiment of the present invention. Detailed Embodiments

[0027] To make the objectives, technical solutions and advantages of the embodiments of the present invention clearer, the following will clearly and completely describe the technical solutions in the embodiments of the present invention with reference to the drawings in the embodiments of the present invention. Obviously, the described embodiments are some but not all of the embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts fall within the scope of protection of the present invention.

[0028] Unless otherwise specified, various raw materials, reagents, instruments, and equipment used in the present invention can be obtained through market purchase or can be prepared by existing methods.

[0029] In a first aspect, the present invention provides a compound traditional Chinese medicine preparation of Lithospermum erythrorhizon, and the compound traditional Chinese medicine preparation of Lithospermum erythrorhizon includes a traditional Chinese medicine composition and pharmaceutical excipients; calculated by weight parts, the traditional Chinese medicine composition includes the following raw materials:

[0030] 55 - 75 parts of Lithospermum erythrorhizon, 10 - 20 parts of Poria cocos, and 25 - 40 parts of Rabdosia lophanthoides var. gerardiana.

[0031] The embodiment of the present invention provides a compound traditional Chinese medicine preparation of Lithospermum erythrorhizon. The compound traditional Chinese medicine preparation of Lithospermum erythrorhizon provided by the present invention uses a traditional Chinese medicine composition mainly composed of Lithospermum erythrorhizon and compounded with appropriate amounts of Poria cocos and Rabdosia lophanthoides var. gerardiana as the active ingredient. Lithospermum erythrorhizon is used as the main drug, and its effect of promoting blood circulation and removing blood stasis can improve the microcirculation of the heart and reduce myocardial ischemia and injury caused by myocardial hypertrophy. Supplementary with the effects of Poria cocos in promoting diuresis and excreting dampness, strengthening the spleen and calming the heart, it helps to reduce the burden on the heart and promote the recovery of heart function. And the effect of Rabdosia lophanthoides var. gerardiana in clearing heat and detoxifying can reduce heart inflammation, reduce the damage of inflammatory factors to myocardial cells, and protect myocardial cells. The three complement each other and have synergistic effects. The results of animal experiments show that this traditional Chinese medicine composition can effectively inhibit the increase in heart weight in a mouse model of myocardial hypertrophy and significantly reduce the level of serum LDH (lactate dehydrogenase) in it. It not only provides a new means for the clinical treatment of hypertrophic cardiomyopathy but also further broadens the application scope of these traditional Chinese medicines in the medical field.

[0032] In some specific embodiments, calculated by weight parts, the traditional Chinese medicine composition includes the following raw materials:

[0033] 60.5 parts of Lithospermum erythrorhizon, 14 parts of Poria cocos, and 32 parts of Rabdosia lophanthoides var. gerardiana.

[0034] In some specific embodiments, calculated by weight parts, the traditional Chinese medicine composition includes the following raw materials:

[0035] 55 parts of Lithospermum erythrorhizon, 10 parts of Poria cocos, and 25 parts of Rabdosia lophanthoides var. gerardiana.

[0036] In some specific embodiments, calculated by weight parts, the traditional Chinese medicine composition includes the following raw materials:

[0037] 75 parts of Lithospermum erythrorhizon, 20 parts of Poria cocos, and 40 parts of Rabdosia lophanthoides var. gerardiana.

[0038] In some specific embodiments, the dosage form of the compound traditional Chinese medicine preparation of Lithospermum erythrorhizon includes tablets, capsules, decoctions, or granules.

[0039] In some specific embodiments, the pharmaceutical excipients include dextrin (CAS: 9004-53-9) and ethanol with a volume percentage of 80-90%, and the weight ratio of the traditional Chinese medicine composition, the dextrin, and the ethanol is 100:(55-65):(9-17).

[0040] In a second aspect, the present invention provides a preparation method for the compound traditional Chinese medicine preparation of Lithospermum erythrorhizon described in any item of the first aspect, as Figure 1 shown, the preparation method for the compound traditional Chinese medicine preparation of Lithospermum erythrorhizon includes the following steps:

[0041] Mix and pulverize Lithospermum erythrorhizon, Poria cocos, and Rabdosia lophanthoides var. gerardiana to obtain a mixed material;

[0042] Add the mixed material to water for reduced-pressure reflux extraction, and then concentrate and dry the obtained water extract to obtain the traditional Chinese medicine composition;

[0043] Mix and prepare the traditional Chinese medicine composition and the pharmaceutical excipients into a formed product to obtain the compound traditional Chinese medicine preparation of Lithospermum erythrorhizon.

[0044] The preparation method for the compound traditional Chinese medicine preparation of Lithospermum erythrorhizon provided by the embodiments of the present invention is simple to operate and suitable for industrial mass production; at the same time, this preparation method is realized based on the compound traditional Chinese medicine preparation of Lithospermum erythrorhizon described in any item of the first aspect. Therefore, it has at least the beneficial effects of the compound traditional Chinese medicine preparation of Lithospermum erythrorhizon described in any item of the first aspect, which will not be elaborated here one by one.

[0045] In some specific embodiments, the working condition parameters of the reduced-pressure reflux extraction include: the pressure is 9-17 kPa, the temperature is 48-60 °C, the time is 60-90 minutes, the number of times is 1-3 times, and the weight ratio of the mixed material to the water is 1:(8-12).

[0046] In some specific embodiments, when the dosage form of the compound traditional Chinese medicine preparation of Lithospermum erythrorhizon is a granule, its preparation method includes the following steps:

[0047] Mix and pulverize Lithospermum erythrorhizon, Poria cocos, and Rabdosia lophanthoides var. gerardiana to obtain a mixed material;

[0048] Add the mixed material to water for reduced-pressure reflux extraction, and then concentrate and dry the obtained water extract to a dry extract state to obtain the traditional Chinese medicine composition;

[0049] Pulverize the traditional Chinese medicine composition and pass it through a 100-mesh sieve, and then add dextrin and ethanol according to the weight ratio for mixing, granulating, drying, and sizing to prepare and form a granule-shaped compound traditional Chinese medicine preparation of Lithospermum erythrorhizon.

[0050] Thirdly, the present invention provides an application of the lithospermum Chinese medicine compound preparation described in any item of the first aspect or the lithospermum Chinese medicine compound preparation prepared by the preparation method of the lithospermum Chinese medicine compound preparation described in any item of the second aspect in the preparation of a drug for treating hypertrophic cardiomyopathy.

[0051] It should be noted that for the component raw materials involved in the lithospermum Chinese medicine compound preparation, its preparation method and application provided in the embodiments of the present invention, if there is no special limitation or specific description, commercially available products can be directly used or self-made by using existing publicly disclosed preparation methods; at the same time, for the steps and parameters involved, if there is no special limitation or specific description, they can be carried out according to the processing technology of existing Chinese medicine compound preparations or directly by using existing equipment, and the present invention document will not elaborate one by one.

[0052] The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and not to limit the scope of the present invention. The experimental methods without specific conditions noted in the following embodiments are usually determined according to current standards. If there is no corresponding current standard, they are carried out according to general conventional conditions or according to the conditions recommended by the manufacturer.

[0053] Example 1

[0054] This example provides a lithospermum Chinese medicine compound preparation, and the lithospermum Chinese medicine compound preparation includes a Chinese medicine composition and a pharmaceutical excipient;

[0055] Calculated by weight parts, the Chinese medicine composition includes the following raw materials:

[0056] 60.5 parts of lithospermum, 14 parts of poria cocos and 32 parts of rabdosia lophanthoides;

[0057] The pharmaceutical excipient includes dextrin and ethanol with a volume percentage of 88%, and the weight ratio of the Chinese medicine composition, the dextrin and the ethanol is 100:60:13.

[0058] The preparation method of the above-mentioned lithospermum Chinese medicine compound preparation includes the following steps:

[0059] Step (1): Mix and pulverize lithospermum, poria cocos and rabdosia lophanthoides to obtain a mixture;

[0060] Step (2): Add the mixture obtained in step (1) into water for reduced-pressure reflux extraction, with a pressure of 13 kPa, a temperature of 55 °C, a time of 70 minutes, and the number of times is 2 times. The weight ratio of the mixture and the water is 1:10. Then, concentrate and dry the obtained water extract to a dry extract state to obtain the Chinese medicine composition;

[0061] Step (3): Pulverize the traditional Chinese medicine composition obtained in step (2) and sieve it through a 100-mesh sieve. Then, add dextrin and ethanol according to the weight ratio for mixing, granulating, drying, and sizing to obtain the compound preparation of Lithospermum erythrorhizon.

[0062] The traditional Chinese medicine composition in the compound preparation of Lithospermum erythrorhizon provided in this example is denoted as active ingredient A.

[0063] Example 2

[0064] This example provides a compound preparation of Lithospermum erythrorhizon, which includes a traditional Chinese medicine composition and pharmaceutical excipients.

[0065] By weight, the traditional Chinese medicine composition includes the following raw materials:

[0066] 55 parts of Lithospermum erythrorhizon, 10 parts of Poria cocos, and 25 parts of Rabdosia lophanthoides var. gerardiana.

[0067] The pharmaceutical excipients include dextrin and ethanol with a volume percentage of 80%. The weight ratio of the traditional Chinese medicine composition, dextrin, and ethanol is 100:55:9.

[0068] The preparation method of the above compound preparation of Lithospermum erythrorhizon includes the following steps:

[0069] Step (1): Mix and pulverize Lithospermum erythrorhizon, Poria cocos, and Rabdosia lophanthoides var. gerardiana to obtain a mixed material.

[0070] Step (2): Add the mixed material obtained in step (1) to water for reduced-pressure reflux extraction at a pressure of 9 kPa, a temperature of 48 °C, for 90 minutes, twice. The weight ratio of the mixed material to water is 1:8. Then, concentrate and dry the obtained water extract to a dry extract state to obtain the traditional Chinese medicine composition.

[0071] Step (3): Pulverize the traditional Chinese medicine composition obtained in step (2) and sieve it through a 100-mesh sieve. Then, add dextrin and ethanol according to the weight ratio for mixing, granulating, drying, and sizing to obtain the compound preparation of Lithospermum erythrorhizon.

[0072] The traditional Chinese medicine composition in the compound preparation of Lithospermum erythrorhizon provided in this example is denoted as active ingredient B.

[0073] Example 3

[0074] This example provides a compound preparation of Lithospermum erythrorhizon, which includes a traditional Chinese medicine composition and pharmaceutical excipients.

[0075] By weight, the traditional Chinese medicine composition includes the following raw materials:

[0076] 75 parts of Lithospermum erythrorhizon, 20 parts of Poria cocos, and 40 parts of Rabdosia lophanthoides var. gerardiana.

[0077] The pharmaceutical excipients include dextrin and ethanol with a volume percentage of 90%, and the weight ratio of the traditional Chinese medicine composition, the dextrin and the ethanol is 100:65:17.

[0078] The preparation method of the above-mentioned Lithospermum erythrorhizon traditional Chinese medicine compound preparation comprises the following steps:

[0079] Step (1): Mix and pulverize Lithospermum erythrorhizon, Poria cocos and Rabdosia lophanthoides var. gerardiana to obtain a mixture.

[0080] Step (2): Add the mixture obtained in step (1) into water for reduced-pressure reflux extraction, with a pressure of 17 kPa, a temperature of 60 °C, a time of 60 minutes, and the number of times being 2 times. The weight ratio of the mixture to the water is 1:12. Then, concentrate and dry the obtained water extract to a dry extract state to obtain the traditional Chinese medicine composition.

[0081] Step (3): Pulverize the traditional Chinese medicine composition obtained in step (2) and pass it through a 100-mesh sieve. Then, add dextrin and ethanol according to the weight ratio for mixing, granulating and drying, and sizing to obtain the Lithospermum erythrorhizon traditional Chinese medicine compound preparation.

[0082] The traditional Chinese medicine composition in the Lithospermum erythrorhizon traditional Chinese medicine compound preparation provided in this example is denoted as active ingredient C.

[0083] Comparative Example 1

[0084] This example provides a traditional Chinese medicine preparation and its preparation method, which is only different from Example 1 in that: the active ingredient of the traditional Chinese medicine preparation is prepared only from Lithospermum erythrorhizon as the raw material; the remaining steps and parameters are the same.

[0085] This example provides a traditional Chinese medicine preparation, which comprises a traditional Chinese medicine extract and pharmaceutical excipients;

[0086] Calculated by weight parts, the traditional Chinese medicine extract comprises the following raw materials:

[0087] 60.5 parts of Lithospermum erythrorhizon;

[0088] The pharmaceutical excipients include dextrin and ethanol with a volume percentage of 88%, and the weight ratio of the traditional Chinese medicine extract, the dextrin and the ethanol is 100:60:13.

[0089] The preparation method of the above-mentioned traditional Chinese medicine preparation comprises the following steps:

[0090] Step (1): Pulverize Lithospermum erythrorhizon, and then add it into water for reduced-pressure reflux extraction, with a pressure of 13 kPa, a temperature of 55 °C, a time of 70 minutes, and the number of times being 2 times. The weight ratio of Lithospermum erythrorhizon to the water is 1:10. Then, concentrate and dry the obtained water extract to a dry extract state to obtain the traditional Chinese medicine extract.

[0091] Step (2): Crush the Chinese medicine extract obtained in step (1) and sieve it through a 100-mesh sieve, then add dextrin and ethanol according to the weight ratio for mixing, granulating, drying, and sizing to obtain the Chinese medicine preparation.

[0092] The Chinese medicine extract in the Chinese medicine preparation provided in this example is denoted as active ingredient D.

[0093] Comparative Example 2

[0094] This example provides a Chinese medicine preparation and its preparation method, which is only different from Example 1 in that: the active ingredient of the Chinese medicine preparation is prepared only from Poria cocos; the remaining steps and parameters are the same.

[0095] This example provides a Chinese medicine preparation, which includes a Chinese medicine extract and pharmaceutical excipients;

[0096] By weight, the Chinese medicine extract includes the following raw materials:

[0097] 14 parts of Poria cocos;

[0098] The pharmaceutical excipients include dextrin and ethanol with a volume percentage of 88%, and the weight ratio of the Chinese medicine extract, the dextrin, and the ethanol is 100:60:13.

[0099] The preparation method of the above Chinese medicine preparation includes the following steps:

[0100] Step (1): Crush Poria cocos, then add it to water for vacuum reflux extraction, with a pressure of 13 kPa, a temperature of 55 °C, a time of 70 minutes, and 2 times. The weight ratio of Poria cocos to water is 1:10. Then concentrate and dry the obtained water extract to a dry extract state to obtain the Chinese medicine extract;

[0101] Step (2): Crush the Chinese medicine extract obtained in step (1) and sieve it through a 100-mesh sieve, then add dextrin and ethanol according to the weight ratio for mixing, granulating, drying, and sizing to obtain the Chinese medicine preparation.

[0102] The Chinese medicine extract in the Chinese medicine preparation provided in this example is denoted as active ingredient E.

[0103] Comparative Example 3

[0104] This example provides a Chinese medicine preparation and its preparation method, which is only different from Example 1 in that: the active ingredient of the Chinese medicine preparation is prepared only from Isodon lophanthoides var. gerardianus; the remaining steps and parameters are the same.

[0105] This example provides a Chinese medicine preparation, which includes a Chinese medicine extract and pharmaceutical excipients;

[0106] By weight, the Chinese medicine extract includes the following raw materials:

[0107] 32 parts of Rabdosia lanceolata var. lanceolata

[0108] The pharmaceutical excipients include dextrin and ethanol with a volume percentage of 88%. The weight ratio of the traditional Chinese medicine extract, the dextrin and the ethanol is 100:60:13.

[0109] The preparation method of the above traditional Chinese medicine preparation comprises the following steps:

[0110] Step (1): Rabdosia lanceolata var. lanceolata is crushed, and then added to water for extraction by decompression reflux. The pressure is 13 kPa, the temperature is 55 °C, the time is 70 minutes, and the number of times is 2 times. The weight ratio of Rabdosia lanceolata var. lanceolata to the water is 1:10. Then, the obtained water extract is concentrated and dried to a dry extract state to obtain the traditional Chinese medicine extract.

[0111] Step (2): The traditional Chinese medicine extract obtained in step (1) is crushed and passed through a 100-mesh sieve, and then dextrin and ethanol are added according to the weight ratio for mixing, granulating and drying, and sizing to obtain the traditional Chinese medicine preparation.

[0112] The traditional Chinese medicine extract in the traditional Chinese medicine preparation provided in this example is denoted as active ingredient F.

[0113] Comparative Example 4

[0114] This example provides a traditional Chinese medicine compound preparation of Lithospermum erythrorhizon and its preparation method. The difference from Example 1 is only that: the weight portion of Poria cocos is adjusted to 35 parts, and the weight portion of Rabdosia lanceolata var. lanceolata is adjusted to 11 parts; the remaining steps and parameters are the same.

[0115] The traditional Chinese medicine composition in the traditional Chinese medicine compound preparation of Lithospermum erythrorhizon provided in this example is denoted as active ingredient G.

[0116] Test Example

[0117] In this example, according to the test method disclosed in the prior art, the active ingredients A - G in the traditional Chinese medicine preparations obtained in Examples 1 - 3 and Comparative Examples 1 - 4 are tested for the effect of treating hypertrophic cardiomyopathy to evaluate their curative effects.

[0118] Test method:

[0119] 1. Animal grouping and model establishment

[0120] 90 healthy Kunming mice, half male and half female, are randomly divided into 9 groups, with 10 mice in each group, namely: blank control group, model control group, and treatment groups of active ingredients A - G (a total of 7 groups).

[0121] Except for the blank control group, mice in other groups were subcutaneously injected with isoprenaline hydrochloride injection to establish a myocardial hypertrophy disease model. The injection protocol was as follows: the dose on the first day was 40 mg / kg, 20 mg / kg on the second day, 10 mg / kg on the third day, and 10 mg / kg was maintained starting from the fourth day, once a day for 14 consecutive days.

[0122] The blank control group was subcutaneously injected with an equal volume of normal saline every day as a control.

[0123] After successful modeling, compared with the blank control group, the left ventricular weight index (LVWI) of the model control group mice should increase significantly, meeting the myocardial hypertrophy model criteria in the second edition of "Pharmacological Experiment Methodology".

[0124] 2. Drug administration

[0125] Drug administration was carried out simultaneously with modeling.

[0126] Four hours after injecting isoprenaline hydrochloride injection every morning, the 7 treatment groups were respectively given active ingredients A - G by gavage for treatment, and the dosage was 50 mg / kg, once a day.

[0127] The blank control group and the model control group were given an equal volume of normal saline by gavage, once a day for 4 consecutive weeks.

[0128] 3. Index detection

[0129] After the last drug administration, the mice were fasted but allowed to drink water for 12 hours.

[0130] The body weight (BW) of the mice was measured, and the mice were sacrificed by taking blood from the eyeballs.

[0131] The chest cavity was quickly opened to take out the heart, the residual blood was washed with pre - cooled normal saline, and after blotting with filter paper, the left ventricle was separated and the left ventricular weight (LVW) was measured.

[0132] The left ventricular weight index was calculated (LVWI = LVW / BW, unit: mg / g).

[0133] The test results are shown in Table 1.

[0134] Table 1

[0135]

[0136] As can be seen from Table 1, compared with Comparative Examples 1-4, the inhibitory effect of active ingredients A-C in the Lithospermum officinale Chinese herbal compound preparation provided in Examples 1-3 of the present invention on the increase in heart weight of the myocardial hypertrophy mouse model is more obvious, which can effectively slow down or even reverse the process of myocardial hypertrophy, thereby significantly alleviating the related symptoms of hypertrophic cardiomyopathy. In addition, after taking blood from the mouse eyeballs, it was centrifuged at a speed of 2000 r / min for 10 minutes at 4°C to separate the serum; according to the instructions of the LDH (lactate dehydrogenase) kit, the LDH level in the serum (unit: U / L) was measured. The results showed that: compared with the serum LDH level of the blank control group mice (412 U / L), the serum LDH level of the model group mice increased significantly, reaching 784 U / L, while the LDH of the treatment groups using active ingredients A-G decreased to varying degrees, but the LDH of the treatment group using active ingredient A decreased most significantly, and the serum LDH level of the mice decreased to 427 U / L, indicating that active ingredient A in the Lithospermum officinale Chinese herbal compound preparation provided in Example 1 has the best intervention and treatment effect on mouse myocardial hypertrophy injury.

[0137] In summary, the embodiments of the present invention provide a Lithospermum officinale Chinese herbal compound preparation, its preparation method and application. The Lithospermum officinale Chinese herbal compound preparation provided by the present invention uses a Chinese herbal medicine composition mainly composed of Lithospermum officinale and compounded with appropriate amounts of Poria cocos and Rabdosia lanceolata as active ingredients. The three complement each other and synergistically enhance the effect. The results of animal experiments show that this Chinese herbal medicine composition can effectively inhibit the increase in heart weight of the myocardial hypertrophy mouse model and significantly reduce its serum LDH level, which not only provides a new means for the clinical treatment of hypertrophic cardiomyopathy, but also further broadens the application scope of these Chinese medicinal materials in the medical field.

[0138] The various embodiments of the present invention may exist in the form of a range; it should be understood that the description in the form of a range is only for convenience and brevity, and should not be construed as a rigid limitation on the scope of the present invention; therefore, it should be considered that the described range description has specifically disclosed all possible sub-ranges and single values within that range. For example, it should be considered that the range description from 1 to 6 has specifically disclosed sub-ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., and single numbers within the range, such as 1, 2, 3, 4, 5, and 6, which applies regardless of the range. In addition, whenever a numerical range is indicated herein, it means including any cited number (fraction or integer) within the indicated range.

[0139] The above are only specific embodiments of the present invention, enabling those skilled in the art to understand or implement the present invention. Various modifications to these embodiments will be obvious to those skilled in the art, and the general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to these embodiments shown herein, but rather to the broadest scope consistent with the principles and novel features claimed herein.

Claims

1. A compound preparation of Lithospermum erythrorhizon traditional Chinese medicine, characterized in that, The compound preparation of Lithospermum erythrorhizon traditional Chinese medicine is composed of a traditional Chinese medicine composition and pharmaceutical excipients; calculated by weight parts, the traditional Chinese medicine composition is composed of the following raw materials: 55 - 75 parts of Lithospermum erythrorhizon, 10 - 20 parts of Poria cocos, and 25 - 40 parts of Rabdosia lophanthoides var. gerardiana.

2. The lithospermum Chinese medicine compound preparation according to claim 1, wherein Calculated by weight parts, the traditional Chinese medicine composition is composed of the following raw materials: 60.5 parts of Lithospermum erythrorhizon, 14 parts of Poria cocos, and 32 parts of Rabdosia lophanthoides var. gerardiana.

3. The lithospermum Chinese medicine compound preparation according to claim 1, wherein Calculated by weight parts, the traditional Chinese medicine composition is composed of the following raw materials: 55 parts of Lithospermum erythrorhizon, 10 parts of Poria cocos, and 25 parts of Rabdosia lophanthoides var. gerardiana.

4. The lithospermum officinale traditional Chinese medicine compound preparation according to claim 1, characterized in that, Calculated by weight parts, the traditional Chinese medicine composition is composed of the following raw materials: 75 parts of Lithospermum erythrorhizon, 20 parts of Poria cocos, and 40 parts of Rabdosia lophanthoides var. gerardiana.

5. The lithospermum officinale traditional Chinese medicine compound preparation according to any one of claims 1 to 4, characterized in that, The dosage forms of the compound preparation of Lithospermum erythrorhizon traditional Chinese medicine include tablets, capsules, decoctions or granules.

6. The compound preparation of traditional Chinese medicine of Lithospermum erythrorhizon according to any one of claims 1 to 4, characterized in that The pharmaceutical excipients include dextrin and ethanol with a volume percentage of 80 - 90%, and the weight ratio of the traditional Chinese medicine composition, the dextrin and the ethanol is 100:(55 - 65):(9 - 17).

7. A preparation method of the lithospermum traditional Chinese medicine compound preparation according to any one of claims 1 to 6, characterized in that, The preparation method of the compound preparation of Lithospermum erythrorhizon traditional Chinese medicine includes the following steps: Mix and pulverize Lithospermum erythrorhizon, Poria cocos and Rabdosia lophanthoides var. gerardiana to obtain a mixed material; Add the mixed material into water for reduced - pressure reflux extraction, and then concentrate and dry the obtained water extract to obtain the traditional Chinese medicine composition; Mix and prepare the traditional Chinese medicine composition and the pharmaceutical excipients into a formed product to obtain the compound preparation of Lithospermum erythrorhizon traditional Chinese medicine.

8. The preparation method of the lithospermum traditional Chinese medicine compound preparation according to claim 7, characterized in that, The working condition parameters of the reduced - pressure reflux extraction include: the pressure is 9 - 17 kPa, the temperature is 48 - 60 °C, the time is 60 - 90 minutes, the number of times is 1 - 3 times, and the weight ratio of the mixed material and the water is 1:(8 - 12).

9. Use of the compound preparation of Lithospermum erythrorhizon traditional Chinese medicine according to any one of claims 1 - 6 or the compound preparation of Lithospermum erythrorhizon traditional Chinese medicine prepared by the preparation method of the compound preparation of Lithospermum erythrorhizon traditional Chinese medicine according to any one of claims 7 - 8 in the preparation of a drug for treating hypertrophic cardiomyopathy.

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