Traditional Chinese medicine leaven medicine for treating influenza A virus and preparation method thereof

Abstract

The invention discloses a traditional Chinese medicine leaven medicine for treating influenza A virus and a preparation method thereof. The composition is mainly composed of cornu bubali concentrated powder, artificial musk, calculus bovis factitius, sheep bile, snake bile and pseudo-ginseng and has the effects of clearing away heat and toxic materials, in-vitro experiments show that the inactivation rate of influenza A virus H1N1 is larger than 99.99%, and toxic and side effects are avoided. The traditional Chinese medicine composition is prepared into a lozenge, the lozenge is subjected to high-temperature sterilization, put into a constant-temperature box with the temperature of 35 DEG C and the humidity of 80% to be fermented until fungus coats grow on the lozenge, and then dried. The raw materials are directly or indirectly prepared into various pharmaceutically acceptable dosage forms such as capsules, oral liquid, granules, syrup, tablets, orally disintegrating tablets, effervescent tablets, effervescent granules, dropping pills, aerosol, spray, gargle, mouthwash and the like through conventional processes. The traditional Chinese medicine composition can be clinically used for treating or preventing clinical symptoms such as acute pharyngalgia, cough and fever caused by influenza A virus H1N1 and upper respiratory infection.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine koji agent for treating influenza A virus and its preparation method. The treatment scope includes treating or preventing clinical symptoms such as influenza A virus H1N1, acute sore throat, cough, fever, etc. caused by upper respiratory tract infection. Background Art

[0002] Influenza A is an acute respiratory infectious disease caused by the influenza A virus, with high infectivity and variability. Common symptoms include fever, cough, sore throat, muscle pain, headache, and fatigue. In severe cases, it can cause complications such as pneumonia and acute respiratory distress syndrome (ARDS).

[0003] Regarding influenza A, traditional Chinese medicine theory believes it belongs to the category of epidemic febrile diseases, and the pathogenic warm factors belong to modern viral infectious diseases. The theory of epidemic febrile diseases states that "the pathogenic warm factors are contracted from above" and first invade the upper respiratory tract. When treating by traditional Chinese medicine syndrome differentiation, clearing heat and detoxifying are commonly used in the initial stage. Traditional Chinese medicine has antiviral effects and exerts its functions through multiple components and multiple targets. It can inhibit virus replication, regulate immune function, and have an anti-inflammatory effect, alleviating symptoms. Moreover, it has fewer side effects and adverse reactions. Compared with western medicine antiviral drugs (such as oseltamivir and peramivir), common oral drugs mainly inhibit virus replication and release through a single target (such as neuraminidase), but may cause adverse reactions such as gastrointestinal discomfort.

[0004] Currently, the dosage forms of traditional Chinese medicine for treating influenza A, such as capsules, oral liquids, and granules, all belong to macromolecular traditional Chinese medicine materials, with slow absorption. It is difficult to extract the active ingredients of traditional Chinese medicine to the greatest extent in traditional processes such as decocting, boiling, simmering, refining, steaming, and soaking. The present invention uses the original endophytic fungi in Chinese herbal medicines for fermentation, relatively converting the molecular weight of traditional Chinese medicine into smaller molecules, with faster and more complete absorption. Modern research has found that endophytic fungi fermentation can better reflect the original medicinal properties of drugs and is more conducive to discovering the original medicinal effects of drugs. Currently, the new two-way solid fermentation technology uses external fungal strains for fermentation, which is prone to bacterial infection or changes in some of the original medicinal properties, and has not adopted all-internal fungal fermentation of the essence of the drug. Through internal fungal biological fermentation, it is degraded into small molecule active substances and directly utilized, and can also remove macromolecular impurities, improving the medicinal properties of traditional Chinese medicine. Since small molecule active substances are more likely to pass through the blood-brain barrier and bind to human cell proteins, they often have higher activity than these macromolecular substances. Through the decomposition effect of microorganisms, the toxic substances in traditional Chinese medicine will also be decomposed, thereby reducing the toxic and side effects of the drug.

[0005] Through repeated experiments, the present invention has found that the fungi in traditional Chinese medicinal materials have the characteristic of being heat-resistant and can survive at a high temperature of 126°C. They have strong fermentation ability. Therefore, closed fermentation is carried out without adding external microorganisms after high-temperature sterilization, and only relying on the endogenous fungal microorganisms in the medicinal materials for fermentation. The results show that the closed endogenous fungal microorganism fermentation method can achieve good fermentation effects: maintaining the original drug function, enhancing the drug efficacy, preventing external microorganism infection, and ensuring food safety. Summary of the Invention

[0006] This research aims at the above-mentioned etiological factors and pathogenesis, and uses a Chinese herbal medicine composition with targeted and unique effects against influenza A virus to ferment into a traditional Chinese medicine koji agent. The composition mainly consists of concentrated powder of buffalo horn, artificial musk, artificial bezoar, sheep bile, snake bile, and notoginseng, and has the effect of clearing heat and detoxifying. Clinically, it can be used to treat or prevent clinical symptoms such as influenza A virus H1N1, acute sore throat, cough, fever, etc. caused by upper respiratory tract infection.

[0007] The technical problem to be solved by the present invention is to overcome the deficiencies of the prior art and provide a traditional Chinese medicine koji agent drug and its preparation method that can effectively treat or prevent clinical symptoms such as influenza A virus H1N1, acute sore throat, cough, fever, etc. caused by upper respiratory tract infection and have no toxic and side effects, so as to meet the market demand.

[0008] The technical solution adopted by the present invention to solve its technical problems is: a traditional Chinese medicine koji agent drug for treating or preventing clinical symptoms such as influenza A virus H1N1, acute sore throat, cough, fever, etc. caused by upper respiratory tract infection, including the following raw materials in parts by weight: 5-20 parts of concentrated powder of buffalo horn, 1.2-4.8 parts of artificial musk, 5-20 parts of artificial bezoar, 6-24 parts of sheep bile, 3-12 parts of snake gallbladder, and 30-120 parts of notoginseng powder.

[0009] Buffalo horn powder: It is cold in nature and bitter in taste, and has the effects of clearing heat and detoxifying, cooling blood, and is used for high fever and delirium in febrile diseases. Modern pharmacological research shows that the active ingredients in buffalo horn powder (such as: sterols, amino acids, polypeptides, etc.) have multiple effects such as antiviral, inhibiting virus activity, anti-inflammatory sedation, and immune regulation, and is used as the monarch drug.

[0010] Sheep bile: It is cool in nature and bitter in taste, and has the effect of clearing heat and detoxifying, and is used to treat sore throat, cough, etc. Modern research shows that sheep bile contains a large amount of beneficial ingredients such as vitamins, amino acids, fatty acids, etc., which can effectively inhibit the reproduction and activity of viruses; bile acids can destroy the virus envelope and inhibit its replication and infection ability, especially more obvious for enveloped viruses (such as: influenza virus); the active ingredients in sheep bile may enhance the immune system function and indirectly help the body resist virus infection; the anti-inflammatory characteristics of sheep bile help to reduce the inflammatory reaction caused by virus infection and relieve symptoms.

[0011] Snake gallbladder: It is cool in nature and bitter in taste, with the efficacy of clearing heat and detoxifying. The main component of snake gallbladder is bile acid, which has a strong detoxifying effect. It can detoxify some chemical and biological toxins and promote the decomposition and metabolism of toxins, thus achieving the efficacy of clearing heat and detoxifying. The components of snake gallbladder also contain a variety of antibacterial and antiviral compounds, among which the most common are bile acids with less toxicity, nitramic acid, nitramide aldehyde and other substances. These substances can effectively inhibit the growth and reproduction of a variety of pathogens, including bacteria, fungi and viruses.

[0012] Artificial bezoar: It is cool in nature and sweet in taste, with the efficacy of clearing heat and detoxifying, resolving phlegm and calming convulsions. The main components include bovine bile powder, cholic acid, ursodeoxycholic acid, taurine, bilirubin, cholesterol, etc.

[0013] Bilirubin is present in sheep bile, snake gallbladder and artificial bezoar, which has the functions of antioxidant and antiviral. It is used as an assistant drug in the formula to treat cough and sore throat in combination with the above three drugs, in order to achieve a stronger effect of clearing heat and detoxifying.

[0014] Artificial musk: It has an antiviral effect. It can inhibit the replication of viruses, reduce the invasion of viruses, regulate the immune system and enhance the body's immunity.

[0015] Notoginseng: It has an antiviral effect. The main active components of notoginseng include saponin compounds (such as ginsenoside Rb1, Ra1, etc.); polysaccharides, flavonoid compounds, amino acids and trace elements, etc. These components can enhance the activity of immune cells, promote the secretion of cytokines, and improve the body's antiviral ability; notoginsenoside can interfere with the enzymes and proteins required for virus replication and inhibit the proliferation of viruses in host cells; the antioxidant components in notoginseng can scavenge free radicals, reduce the oxidative damage caused by viruses, and protect cells. Notoginseng can induce the production of antiviral proteins such as interferon, enhance the body's defense ability against viruses, and has broad-spectrum antiviral potential. It is commonly used in the adjuvant treatment of various virus infections.

[0016] The combination of artificial musk and notoginseng can better improve the antiviral effect and enhance the function of regulating immunity.

[0017] The traditional Chinese medicine composition fermentation starter of the present invention is selected from traditional Chinese medicines for clearing heat and detoxifying. It has an antiviral drug group that can play their respective pharmacological effects and also have a mutual synergistic effect. Through fermentation and processing, the medicinal efficacy is increased and the toxicity is reduced. It has a significant curative effect in clinically treating symptoms such as acute sore throat, cough, fever, etc. caused by influenza or upper respiratory tract infection. Through in vitro virus H1N1 inactivation experiment, the virus inactivation rate is as high as 99.99%. It can effectively inhibit the H1N1 influenza virus, and has no toxic and side effects. It can be used as a general prescription for treatment and prevention during the epidemic period, and the dosage form and preparation process are suitable for large-scale industrial production.

[0018] The raw materials of the traditional Chinese medicine koji agent of the present invention are: 5-20 parts of concentrated water buffalo horn powder, 1.2-4.8 parts of artificial musk, 5-20 parts of artificial bezoar, 6-24 parts of sheep bile, 3-12 parts of snake bile, and 30-120 parts of notoginseng powder.

[0019] The preparation method of the medicine of the present invention is as follows: (1) Dissolve snake bile and sheep bile in water, filter and concentrate to obtain clear paste; (2) Mix artificial musk, artificial bezoar powder, concentrated water buffalo horn powder, and notoginseng powder. The above four kinds of medicinal powders are mixed with (1) to make lozenges, and then sterilized by an autoclave under aseptic operation and directly put into an incubator for fermentation until the medicine is covered with mycelia, which means the fermentation is complete. After drying, grind it into powder to obtain the product.

[0020] The koji agent medicine for treating influenza A virus is characterized in that: the dosage form of the composition is: capsule, oral liquid, granule, syrup, sugar cube, tablet, orally disintegrating tablet, effervescent tablet, effervescent granule, dropping pill, aerosol, spray, gargle, mouthwash.

[0021] The traditional Chinese medicine composition of the present invention is an empirical formula that combines the treatment of epidemic febrile diseases with heat-clearing and detoxifying as the main treatment in traditional Chinese medicine and the screening and combination of antiviral traditional Chinese medicines based on modern pharmacology. It exerts its effect through fermentation to enhance the antiviral effect of the medicine. This formula is used to treat or prevent clinical symptoms such as influenza A virus H1N1, acute sore throat, cough, fever, etc. caused by upper respiratory tract infection. The curative effect is exact, and there are no toxic and side effects. During the epidemic period, it is effective as a general formula for both treatment and prevention. The dosage form and preparation process are suitable for large-scale industrial production. Detailed implementation mode

[0022] The traditional Chinese medicine koji agent medicine for treating influenza A virus of the present invention includes the following raw materials in parts by weight: 5-20 parts of concentrated water buffalo horn powder, 1.2-4.8 parts of artificial musk, 5-20 parts of artificial bezoar, 6-24 parts of sheep bile, 3-12 parts of snake bile, and 30-120 parts of notoginseng powder.

[0023] Implementation mode 1: (1) Weigh 5g of concentrated water buffalo horn powder, 1.2g of artificial musk, 5g of artificial bezoar, 6g of sheep bile, 3g of snake bile, and 30g of notoginseng powder as raw material medicine, and the total of the above six kinds of medicines is 50.2g; (2) Dissolve snake bile and sheep bile in water, filter and concentrate them into clear paste; (3)Artificial musk, artificial bezoar powder, concentrated buffalo horn powder, and notoginseng powder. The powder of the above four medicinal materials is mixed with (1) to make pills, which are sterilized in an autoclave at a sterilization temperature of 126 °C and a pressure of 2.35 mpa for 30 minutes. After sterilization by aseptic operation, it is directly put into an incubator for fermentation at a fermentation temperature of 30 to 40 °C and a fermentation humidity of 80% to 100%. Fermentation is completed when the medicinal materials are covered with mycelia. After drying in a drying oven, it is ground into powder for standby. Add β-cyclodextrin, heat to dissolve, stir, filter, and spray dry. The inlet air temperature of the hot air is 180 °C, and the outlet air temperature is 80 °C. Add flavoring agents to the dry powder, mix well, granulate the material dry at 40 °C, size the granules, and pack them into bags to obtain the granule for treating influenza A virus of the present invention.

[0024] Embodiment 2: (1)Weigh the raw material medicine: 5 g of concentrated buffalo horn powder, 1.2 g of artificial musk, 5 g of artificial bezoar, 6 g of sheep bile, 3 g of snake bile, and 30 g of notoginseng powder. The total weight of the above six medicinal materials is 50.2 g. (2)Dissolve and filter snake bile and sheep bile with water and concentrate them into clear paste. (3)Artificial musk, artificial bezoar powder, concentrated buffalo horn powder, and notoginseng powder. The powder of the above four medicinal materials is mixed with (1) to make pills, which are sterilized in an autoclave at a sterilization temperature of 126 °C and a pressure of 2.35 mpa for 30 minutes. After sterilization by aseptic operation, it is directly put into an incubator for fermentation at a fermentation temperature of 30 to 40 °C and a fermentation humidity of 80% to 100%. Fermentation is completed when the medicinal materials are covered with mycelia. After drying in a drying oven, it is ground into powder for standby. Add sucrose (>450 g), flavoring agents (stevioside, saccharin sodium, acesulfame potassium, glycyrrhizin, cyclohexylsulfamic acid, asparagine, polyol, aspartame, menthol, various flavors and various fruit flavoring agents, with a dosage of 0.1 - 10%) and preservatives (sorbic acid and its potassium and sodium salts with a dosage of <0.3%, methylparabens with a dosage of <0.05%) and other excipients, boil, add water to dilute to 1000 ml, refine (various clarifying agents such as clarifying agent 101, tubular centrifugation, plate and frame filtration), filter, mix well, and pack (the packaging materials are glass bottles and plastic bottles) to obtain the syrup for treating influenza A virus.

[0025] Experimental Example 1: Identification test of residual disinfectant chemical neutralization method (1)Detection method: "Disinfection Technical Specification" 2002 Edition - 2.1.1.10.5 (2)Neutralization method: PBS solution containing 3% Tween - 80, 0.5% sodium thiosulfate, 0.5% L - histidine, 0.5% peptone, 0.85% sodium chloride, 1.43% lecithin, and 0.1% cysteine (3)Test results: The logarithm of the average virus titer of Group 1 (lgTCID / mL) was <1.50, the logarithm of the average virus titer of Group 2 (lgTCID50 / mL) was 1.74, and the average virus titers (lgTCID50 / mL) of Group 3, Group 4, and Group 5 were similar, with error rates among the three groups being 1.1%, 12%, and 1.6% respectively. Note: The cells in the negative control group grew well.

[0026] Experimental Example 2: Efficacy of traditional Chinese medicine koji agent against influenza A virus H1N1 in vitro, i.e., inactivation experiment of influenza A virus H1N1 (1) Detection method: "Disinfection Technical Specification" 2002 Edition - 2.1.1.10.7 (2) Test results: The inactivation logarithmic index was greater than 4.0, that is, from 10 of the initial positive control virus 6 10 was inactivated 4 , and the surviving virus was less than 100. Therefore, the virus inactivation rate was greater than 99.99%, and it could effectively kill H1N1 virus. Note: The cells in the negative control group grew well.

[0027] Experimental Example 3: Monitoring experiment of aflatoxin B1 in traditional Chinese medicine koji agent Result: Aflatoxin B1 was not detected, meeting the aflatoxin-free index.

[0028] The above content is a further detailed description of the present invention in combination with specific preferred implementation manners. It cannot be determined that the specific implementation of the present invention is only limited to these descriptions. For those of ordinary skill in the technical field to which the present invention pertains, without departing from the concept of the present invention, several simple deductions or substitutions can be made, and all should be regarded as belonging to the protection scope of the present invention.

Claims

1. A traditional Chinese medicine preparation for treating influenza A virus, comprising the following raw materials in parts by weight: 5-20 parts of buffalo horn concentrated powder, 1.2-4.8 parts of artificial musk, 5-20 parts of artificial bezoar, 6-24 parts of sheep bile, 3-12 parts of snake gall, and 30-120 parts of Panax notoginseng powder.

2. A method for preparing the medicament according to claim 1, comprising the following steps: (1) Dissolve snake gallbladder and sheep gallbladder in water, filter and concentrate to obtain a clear paste; (2) Artificial musk, artificial bezoar powder, buffalo horn concentrated powder, Panax notoginseng powder. The above four medicinal powders are mixed with (1) to form tablets. After sterilization in a high-pressure sterilizer, they are directly placed in a constant temperature box for fermentation until the drugs are covered with mycelium. After drying, they are ground into powder.

3. The method for preparing the influenza A virus syrup according to claim 2, characterized in that In the step (2), the high pressure sterilizer is sterilized at a sterilization temperature of 126° C. and 2.35 MPa for 30 minutes, and then directly enters the constant temperature box for fermentation, with a fermentation temperature of 30 to 40° C. and a fermentation humidity of 80% to 100%.

4. The drug for treating influenza A virus according to claims 1 to 3, characterized in that: The dosage form of the composition is capsule, oral liquid, granule, syrup, sugar block, tablet, orodisintegrating tablet, effervescent tablet, effervescent granule, pill, aerosol, spray, rinse solution and mouthwash.

5. The drug for treating influenza A virus according to claims 1 to 5, characterized in that: It can be used clinically to treat clinical symptoms such as acute sore throat, cough, fever, etc. caused by influenza A virus H1N1 and upper respiratory tract infection.

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