CN105663661A - Traditional Chinese medicinal composition for treating warm pathogenic toxin invading heart type myocarditis and preparation method of traditional Chinese medicinal composition - Google Patents

Abstract

The invention relates to a traditional Chinese medicine composition for treating myocarditis and a preparation method thereof, belonging to the fields of health food and traditional Chinese medicine. It is prepared from Scrophulariae, Ophiopogon japonicus, Radix Pseudostellariae, Folium Isatidis, Banlangen, Shandougen, Scutellaria, Bupleurum, Puerariae, Forsythia, Licorice, Guizhi, etc., and can be mixed with pharmaceutically applicable carriers Mixing, various preparations prepared according to specific processes. The invention also includes an industrially applicable preparation method. Oral preparations, such as solid or liquid, made of medically acceptable auxiliary materials prepared by the preparation method disclosed in the present invention. The composition has the functions of clearing heat and detoxifying, protecting heart and nourishing yin. For viral myocarditis, high fever, palpitations, sore throat and viral colds in the acute stage.

Description

A kind of medicinal composition for treating warm-heat pathogenic poisoning heart type myocarditis and preparation method thereof

technical field

The invention relates to a medicinal composition for treating heart-type myocarditis caused by warm-heat evil poison and a preparation method thereof, belonging to the fields of health food and traditional Chinese medicine.

Background technique

Viral myocarditis refers to myocarditis caused by myotropic virus infection with non-specific interstitial inflammation of the myocardium as the main lesion. Viral myocarditis is the most important disease in infectious cardiomyopathy, and its pathogenesis is related to viral infection, cellular immunity and autoimmune abnormalities. At present, it is believed that viral myocarditis is mainly caused by the invasion of the heart by Coxsackie group B virus. The main pathological changes are myocardial inflammatory necrosis and interstitial mononuclear cell infiltration, and it is one of the common clinical cardiovascular diseases. Mostly in children and adolescents, the incidence rate is high and the course of disease is long.

Clinically, it is characterized by the appearance or onset of acute viral infection, accompanied by cardiac symptoms such as palpitations, chest tightness, chest pain, shortness of breath, and abnormal changes in the electrocardiogram. The disease can occur at any age, but it is more common in adolescents, more men than women, and summer and autumn are the seasons of high incidence. The acute phase is within six months of onset, the recovery period is six months to one year, and the chronic phase is more than one year. Most patients with myocarditis can be cured. Some patients have signs of abnormal cardiac changes and electrocardiograms to a certain extent, but the condition remains unchanged for a long time. Very few patients died in the acute phase due to severe arrhythmia, acute heart failure and cardiogenic shock.

Modern medicine mainly adopts methods such as symptomatic treatment, control of symptoms, and nourishing myocardium to the treatment of this disease, but there is no special effect yet, while the treatment of traditional Chinese medicine shows obvious advantages. In the study of Chinese medicine treatment of viral myocarditis, there are 45 traditional Chinese medicines that are used frequently, mainly for tonic medicine, blood circulation promoting and stasis medicine, heat clearing medicine, exterior medicine, phlegm medicine, tranquilizing medicine, and interior warming medicine. It is concluded that the main drugs for viral myocarditis are to nourish qi and nourish yin, clear away heat and detoxify, promote blood circulation and remove blood stasis, and dry dampness and resolve phlegm.

Many Chinese herbal medicines have the effects of anti-virus, anti-inflammation, and improving the body's immunity. The use of Chinese herbal medicines to prevent and treat viral diseases has become a research hotspot today. The new compound drug of traditional Chinese medicine is the main body of new drug research of traditional Chinese medicine, embodying the theoretical characteristics of traditional Chinese medicine, the quality standard research of new compound drug is one of the main contents of pharmaceutical research, and it is also the key content of pharmaceutical evaluation of new drug. In recent years, the research level of new compound medicines of traditional Chinese medicine has been greatly improved. Especially in recent years, due to the improvement of the preparation process of traditional Chinese medicine, the research on the treatment of viral myocarditis by extracts of traditional Chinese medicine or active ingredients of traditional Chinese medicine has gradually increased, and some of them have been developed into Chinese patent medicine preparations.

The theory of traditional Chinese medicine believes that wind is the root of all diseases, and good deeds change several times. It often carries warm and evil poison from the mouth and nose, and the throat is the door of the lung system. The evil poison invades and bears the brunt of it. It is clinically found that most patients with viral myocarditis have a history of chronic pharyngitis, are often invaded by exogenous pathogens, multiply and accumulate toxins to invade the heart, inhibit the heart, body and function, and cause the disease. Therefore, this infection route must be completely cut off. In terms of treatment, special attention should be paid to the treatment of chronic pharyngitis. Therefore, there is a saying that "pharyngitis will not be eliminated in a day, and viral myocarditis will not stop in a day".

Contents of the invention

The object of the present invention is to provide a kind of Chinese medicine composition for treating myocarditis.

Another object of the present invention is to provide a preparation method of the preparation.

The present invention is achieved through the following several technical solutions:

Technical solution one includes the following steps:

(1) Extraction: add water to Bupleurum radix and Guizhi medicinal materials and keep boiling for 4-10 hours, extract the mixed volatile oil by steam distillation, and use the volatile oil, medicinal dregs and extracted aqueous solution for later use; take the remaining raw materials such as Scrophulariaceae scrophulariae, and extract the volatile oil Combine the dregs, decoct and extract 1 to 3 times, separate the extracts, combine, and filter; combine the filtrate with the above aqueous solution, concentrate under reduced pressure to a clear paste with a relative density of 1.00 to 1.20 (50 to 90°C), put Cold; take the above concentrate, add ethanol until the alcohol content reaches 50-80%, let it stand, and filter; the filtrate is decompressed to recover ethanol, concentrate to a clear paste with a relative density of about 1.10-1.40 (50-90°C), add A certain amount of water is heated and filtered to obtain a solution .

(2) the solution , volatile oil, add appropriate auxiliary materials, and make oral preparations such as mixtures, tablets, capsules, granules, pills, syrups, and decoctions according to conventional processes.

The second technical solution includes the following steps:

(1) Extraction: add water to Bupleurum radix and Guizhi medicinal materials and keep boiling for 4-10 hours, extract the mixed volatile oil by steam distillation, and use the volatile oil, medicinal dregs and extracted aqueous solution for later use; take the remaining raw materials such as Scrophulariaceae scrophulariae, and extract the volatile oil Combine the dregs, decoct and extract 1 to 3 times, separate the extracts, combine, and filter; combine the filtrate with the above aqueous solution, concentrate under reduced pressure to a clear paste with a relative density of 1.00 to 1.20 (50 to 90°C), put cold; add a certain amount of water, heat, filter to obtain a solution .

(2) the solution , volatile oil, add appropriate auxiliary materials, and make oral preparations such as mixtures, tablets, capsules, granules, pills, syrups, and decoctions according to conventional processes.

Technical solution three includes the following steps:

(1) Extraction: Weigh the medicinal materials according to the prescription, decoct and extract for 1 to 3 times, separate the extracts, combine them, and filter; combine the filtrate with the above aqueous solution, concentrate under reduced pressure to a relative density of 1.00 to 1.20 (50 to 90 ℃) clear paste, let it cool; take the above concentrate, add ethanol until the alcohol content reaches 50-80%, let it stand, and filter; the filtrate is decompressed to recover ethanol, concentrated to a relative density of about 1.10-1.40 (50-90 ℃), add a certain amount of water, heat, and filter to obtain solution Ⅲ.

(2) Add solution III to appropriate excipients, and make oral preparations such as mixtures, tablets, capsules, granules, pills, syrups, and decoctions according to conventional processes.

Technical solution four includes the following steps:

(1) Extraction: Weigh the medicinal materials according to the prescription, decoct and extract for 1 to 3 times, separate the extracts, combine them, and filter; combine the filtrate with the above aqueous solution, concentrate under reduced pressure to a relative density of 1.00 to 1.20 (50 to 90 ℃), let cool; add a certain amount of water, heat, filter to obtain solution IV.

(2) Add solution IV with appropriate auxiliary materials, and make oral preparations such as mixtures, tablets, capsules, granules, pills, syrups, and decoctions according to conventional processes.

detailed description:

The beneficial effects of the present invention will be described below through experimental examples.

Carry out experiment with the mixture of specific embodiment of the present invention.

In vitro experimental results of the present invention:

Materials and Methods

1 Cell line: Rat H9c2 cardiomyocytes were purchased from the Shanghai Cell Bank of the Chinese Academy of Sciences.

Drugs were provided by the Experimental Center of the Affiliated Hospital of Changchun University of Traditional Chinese Medicine. According to the drug concentration required for the experiment, calculate the corresponding Chinese medicine solution and add it to the cell culture dish.

Reagents and instruments

High glucose cell culture medium (DMEM) and 0.25% trypsin were purchased from Gibco; fetal calf serum (MRC) was purchased from Beijing Meilaibo Company; TNF-α, IL-1β, IL-6 ELISA kits and dimethyl sulfoxide ( DMSO) was purchased from Sigma; Escherichia coli lipopolysaccharide was purchased from Shanghai Ji Ning Industrial Co., Ltd.; CO2 incubator was purchased from Japan SANYO, HERAcell240, ThermoELECTROWCORPORATIOW, ultra-clean workbench was purchased from AIRTECH Sujing Group Antai Company, and microplate reader was purchased from SpectraMaxM2 .

method

4.1 Culture and passage of rat H9c2 cardiomyocytes: H9c2 cardiomyocytes were routinely resuscitated and transferred to cell culture dishes for static culture. The medium consists of 10% FBS, penicillin and DMEM. The culture bottle was placed in a volume fraction of 5% CO2 and 37°C under the condition of saturated humidity for 2 to 3 days, and the cells were digested with 2.5g/L trypsin for passage. Cells in the logarithmic growth phase are used to make a single cell suspension at a certain concentration, inoculated in a 96-well plate or a 6-well plate and placed in an incubator for culture.

Modeling: plant the cell suspension in a 6-well plate at a density of 10×10 ⁶ /mL, culture in a 37°C, 5% CO ₂ incubator, observe the cell attachment under a light microscope, and wait until the cells grow to 90% For a single layer, E. coli lipopolysaccharide at a concentration of 20ug/ml can be added to the culture medium to stimulate rat H9c2 cardiomyocytes for 24 hours. Placed in a 5% CO2 incubator at 37°C for 24 hours. Dosing in groups: 24 hours after infection, add medicine for intervention. Normal group: routine cell culture. Model control group: LPS stimulation. Medium-dose preparation group: add preparation concentration to 50 mg/ml and continue to cultivate; preparation high-dose group: add preparation concentration to 100 mg/ml and continue to cultivate.

Contents of TNF-α, IL-1β, and IL-6 in the supernatant of H9c2: The contents of TNF-α, IL-1β, and IL-6 in the cell supernatant were detected by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). Rat H9c2 cardiomyocytes were inoculated into 6-well culture plates at 5×10 ⁴ ·mL-1. When the cells grew to 80% confluence, they were synchronized for 24 hours. According to the experimental grouping, after 24 hours of culture, the cell culture supernatants of each group were collected for detection. The concentrations of TNF-α, IL-1β and IL-6 in the supernatant were determined by ELISA. According to the instructions of the kit, after making the standard curve, set 6 wells in each group, and calculate the corresponding content according to the standard curve of the standard.

Statistical methods: SPSS13.0 statistical software was used, the comparison of the means of multiple samples was carried out by one-way ANO-VA, and the pairwise comparison was carried out by SNK-q test.

result

5.1 Comparison of the content of TNF-α in the H9c2 supernatant (table 1): the TNF-α factor concentration secreted by the H9c2 cardiomyocytes after being stimulated by LPS for 24 hours was significantly higher than that of the normal group, and the concentration was 50mg/ml and 100mg/ml preparations After treatment, the concentration of TNF-α in the intervention group was significantly lower than that in the LPS stimulation group, and the difference was statistically significant (P<0.01).

Table 1

The effect of the preparation on the expression of TNF-α factor in rat H9c2 cardiomyocytes induced by lipopolysaccharide (x±s)

5.2 Comparison of the content of IL-1β in the supernatant of H9c2 (Table 2): the concentration of IL-1β factor secreted by H9c2 stimulated by LPS for 24 hours was significantly higher than that of the normal group, after being treated with the preparations with concentrations of 50mg/ml and 100mg/ml The concentration of IL-1β in the intervention group was significantly lower than that in the LPS stimulation group, and the difference was statistically significant (P<0.01).

Table 2

The effect of the preparation on the expression of IL-1β factor in rat H9c2 cardiomyocytes induced by lipopolysaccharide (x±s)

5.3 Comparison of the content of IL-6 in the supernatant of H9c2 (Table 3): the concentration of IL-6 factor secreted by H9c2 stimulated by LPS for 24 hours was significantly higher than that of the normal group, after being treated with the preparations with concentrations of 50mg/ml and 100mg/ml The IL-6 concentration in the intervention group was significantly lower than that in the LPS stimulation group, and the difference was statistically significant (P<0.01).

table 3

The effect of the preparation on the expression of IL-6 factor in rat H9c2 cardiomyocytes induced by lipopolysaccharide (x±s)

6. Discussion

A large number of studies have shown that the pathogenesis of viral myocarditis is closely related to cytokines [6-9]. At present, TNF-α is recognized as an inflammatory cytokine involved in myocardial injury, and TNF-α is related to the process of myocardial damage and the severity of viral myocarditis closely related.

In this experiment, the expression levels of TNF-α, IL-1β and IL-6 in the culture supernatant of the LPS+preparation group were significantly lower than those of the control group. The results suggested that the preparation had a significant therapeutic effect on viral myocarditis. During the development of viral myocarditis, IL-6 and TNF-α increase in myocardial tissue, and the preparation can inhibit the expression of IL-6 and TNF-α, reduce myocardial necrosis and inflammatory cell infiltration, and reduce the destruction of cell structure. Protection and restoration. The mechanism of action of the preparation for the treatment of viral myocarditis may be: ① direct antiviral effect and induction of interferon, reducing damage to myocardial cells. ② Immunomodulatory effect, limiting immune damage caused by cytotoxic effects mediated by TNF-α, IL-1β, IL-6, etc.

detailed description

The present invention is further described as follows in conjunction with embodiment:

Example 1

The present invention weighs the pharmaceutical components according to the following weight ratio:

100 parts of Folium Isatidis, 100 parts of Radix Isatidis, 50 parts of Scrophulariaceae, 40 parts of Ophiopogon japonicus, 40 parts of Heterophylla heterophylla, 50 parts of mountain bean root, 40 parts of Scutellaria baicalensis, 40 parts of Bupleurum, 40 parts of Pueraria root, 100 parts of forsythia, licorice 40 parts, Guizhi 40 parts.

The preparation process is as follows: adding water to the medicinal materials of Bupleurum radix and Guizhi and keeping them slightly boiled for 6 hours, extracting the mixed volatile oil by steam distillation, using the volatile oil, medicinal residues and distillate for later use; taking other raw materials, combining them with the medicinal residues after extracting the volatile oil, and decocting Boil and extract 3 times, separate the extracts, combine and filter; combine the filtrate with the above aqueous solution, concentrate under reduced pressure to a clear paste with a relative density of 1.05-1.10 (80°C), let it cool; take the above concentrate, add ethanol When the alcohol content reaches 75%, stand still and filter; the filtrate is decompressed to recover ethanol, concentrate to a clear paste with a relative density of about 1.12-1.20 (80°C), add a certain amount of water, heat, and filter to obtain a solution . the solution , volatile oil, add appropriate auxiliary materials, sub-package, sterilize, and get ready.

Example 2

The present invention weighs the pharmaceutical components according to the following weight ratio:

100 parts of Folium Isatidis, 100 parts of Radix Isatidis, 50 parts of Scrophulariaceae, 40 parts of Ophiopogon japonicus, 40 parts of Heterophylla heterophylla, 50 parts of mountain bean root, 40 parts of Scutellaria baicalensis, 40 parts of Bupleurum, 40 parts of Pueraria root, 100 parts of forsythia, licorice 40 parts, Guizhi 40 parts.

The preparation process is as follows: adding water to the medicinal materials of Bupleurum radix and Guizhi and keeping them slightly boiled for 6 hours, extracting the mixed volatile oil by steam distillation, using the volatile oil, medicinal residues and distillate for later use; taking other raw materials, combining them with the medicinal residues after extracting the volatile oil, and decocting Boil and extract 3 times, separate the extracts, combine and filter; combine the filtrate with the above aqueous solution, concentrate under reduced pressure to a clear paste with a relative density of 1.05-1.10 (80°C), let it cool, add a certain amount of water, and heat. filtered to obtain a solution . the solution , volatile oil, add appropriate auxiliary materials, sub-package, sterilize, and get ready.

Example 3

The present invention weighs the pharmaceutical components according to the following weight ratio:

100 parts of Folium Isatidis, 100 parts of Radix Isatidis, 50 parts of Scrophulariaceae, 40 parts of Ophiopogon japonicus, 40 parts of Heterophylla heterophylla, 50 parts of mountain bean root, 40 parts of Scutellaria baicalensis, 40 parts of Bupleurum, 40 parts of Pueraria root, 100 parts of forsythia, licorice 40 parts, Guizhi 40 parts.

The preparation process is as follows: weigh each medicinal material in proportion, decoct and extract three times, separate the extracts, combine them, and filter them; combine the filtrate with the above aqueous solution, concentrate under reduced pressure to a relative density of 1.05-1.10 (80°C) Clear the ointment and let it cool; take the above concentrate, add ethanol until the alcohol content reaches 75%, let it stand, and filter; the filtrate is decompressed to recover ethanol, concentrated to a clear ointment with a relative density of about 1.12-1.20 (80°C), and added A certain amount of water was heated and filtered to obtain solution Ⅲ. The solution III is added with appropriate auxiliary materials, subpackaged and sterilized to obtain the product.

Example 4

The present invention weighs the pharmaceutical components according to the following weight ratio:

100 parts of Folium Isatidis, 100 parts of Radix Isatidis, 50 parts of Scrophulariaceae, 40 parts of Ophiopogon japonicus, 40 parts of Heterophylla heterophylla, 50 parts of mountain bean root, 40 parts of Scutellaria baicalensis, 40 parts of Bupleurum, 40 parts of Pueraria root, 100 parts of forsythia, licorice 40 parts, Guizhi 40 parts.

The preparation process is as follows: weigh each medicinal material in proportion, decoct and extract three times, separate the extracts, combine them, and filter them; combine the filtrate with the above aqueous solution, concentrate under reduced pressure to a relative density of 1.05-1.10 (80°C) Clear the ointment, let it cool, add a certain amount of water, heat, and filter to obtain solution IV. The solution IV is added with appropriate auxiliary materials, subpackaged and sterilized to obtain the product.

Example 5

Implement 1, 2, 3, and 4 in different proportions respectively.

Claims (7)

1. treating a myocarditic Chinese medicine composition, it belongs to technical field of Chinese medicines; It is characterized in that it is formulated by a certain percentage by being mainly composed of Radix Scrophulariae, Radix Ophiopogonis, Radix Pseudostellariae, Folium Isatidis, Radix Isatidis, Radix Sophorae Tonkinensis, Radix Scutellariae, Radix Bupleuri, Radix Puerariae, Fructus Forsythiae, Radix Glycyrrhizae, Ramulus Cinnamomi etc., other oral formulations such as the mixture that is mixed with by special process, tablet, capsule, granule, pill, syrup, soft extract with pharmaceutically suitable carrier.

2. the preparation method of the myocarditic Chinese medicine composition for the treatment of according to claim 1, it is characterised in that said composition includes the raw material of following weight parts: Radix Scrophulariae 30-90 part, Radix Ophiopogonis 30-90 part, Radix Pseudostellariae 30-90 part, Folium Isatidis 90-150 part, Radix Isatidis 90-150 part, Radix Sophorae Tonkinensis 30-90 part, Radix Scutellariae 30-90 part, Radix Bupleuri 30-90 part, Radix Puerariae 90-150 part, Fructus Forsythiae 90-150 part, Radix Glycyrrhizae 30-90 part, Ramulus Cinnamomi 30-90 part.

3. the preparation method of the treatment myocarditis compositions in any of the one of claim 1-2, it is characterised in that weigh raw material according to said ratio; Take Radix Bupleuri, Ramulus Cinnamomi extracts volatile oil, and volatile oil is standby; Other raw material boilings such as medicinal residues and Radix Scrophulariae are extracted, and filter, merging filtrate, it is evaporated to certain relative density, add ethanol to precipitate, divide and take supernatant, decompression recycling ethanol, obtain concentrated solution, add a certain amount of water, heating, filter, adding volatile oil and suitable adjuvant, technique makes the oral formulations such as mixture, tablet, capsule, granule, pill, syrup, soft extract routinely.

4. the preparation method of the treatment myocarditis compositions in any of the one of claim 1-2, it is characterised in that weigh raw material according to said ratio, boiling is extracted, filter, merging filtrate, be evaporated to certain relative density, add ethanol to precipitate, divide and take supernatant, decompression recycling ethanol, obtain concentrated solution, add a certain amount of water, heating, filter, adding suitable adjuvant, technique makes the oral formulations such as mixture, tablet, capsule, granule, pill, syrup, soft extract routinely.

5. the preparation method of the treatment myocarditis compositions in any of the one of claim 1-2, it is characterised in that weigh raw material according to said ratio; Take Radix Bupleuri, Ramulus Cinnamomi extracts volatile oil, and volatile oil is standby; Other raw material boilings such as medicinal residues and Radix Scrophulariae are extracted, and filter, merging filtrate, ultrafiltration, filtrate is concentrated into certain crude drug amount, stands, filtering, add volatile oil and suitable adjuvant, technique makes the oral formulations such as mixture, tablet, capsule, granule, pill, syrup, soft extract routinely.

6. the preparation method of the treatment myocarditis compositions in any of the one of claim 1-2, it is characterized in that weighing raw material according to said ratio, boiling is extracted, and filters, merging filtrate, ultrafiltration, filtrate is concentrated into certain crude drug amount, stands, and filters, adding suitable adjuvant, technique makes the oral formulations such as mixture, tablet, capsule, granule, pill, syrup, soft extract routinely.

7. according to the claim 2-6 composite preparation made, there is heat-clearing and toxic substances removing, protect heart yin nourishing, for viral myocarditis, high heat, cardiopalmus, pharyngalgia and the viral influenza etc. that acute stage occurs.