CN113197904A

CN113197904A - Traditional Chinese medicine active ingredient composition for treating cough and preparation method thereof

Info

Publication number: CN113197904A
Application number: CN202110347687.6A
Authority: CN
Inventors: 庞克坚; 吴志豪
Original assignee: Hetian Uygur Pharmaceutical Co ltd
Current assignee: Hetian Uygur Pharmaceutical Co ltd
Priority date: 2021-03-31
Filing date: 2021-03-31
Publication date: 2021-08-03

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and discloses a traditional Chinese medicine active ingredient composition for treating cough and a preparation method thereof, wherein the traditional Chinese medicine active ingredient composition for treating cough is composed of, by mass, 15-35 parts of tormentic acid, 15-25 parts of alpha-cedrol, 15-40 parts of beta-sitosterol and 18-25 parts of ammonium glycyrrhizinate. The traditional Chinese medicine active ingredient composition for treating cough provided by the invention has a definite basis of drug effect substances, is prepared from tormentic acid, alpha-cedrol, beta-sitosterol and ammonium glycyrrhetate, has a definite structure, fixed components and controllable quality, and lays a foundation for the safety and effectiveness of the traditional Chinese medicine active ingredient composition; the cough relieving traditional Chinese medicine composition has a clear action mechanism, and reduces the stimulation to the cough center by adopting a mode of combining classical pharmacology and system biology research so as to achieve the aim of relieving cough; the composition can improve the disorder of an antioxidant balance system in vivo, effectively remove excessive free radicals in organisms and relieve oxidative damage.

Description

Traditional Chinese medicine active ingredient composition for treating cough and preparation method thereof

Technical Field

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine active ingredient composition for treating cough and a preparation method thereof.

Background

At present, cough is a common respiratory symptom caused by inflammation, foreign bodies, physical or chemical stimulation on the trachea, the bronchial mucosa or the pleura, and has a protective effect of removing respiratory foreign bodies and secretions. The book "Hejianlu & cough treatise" is as follows: the six qi of cold, summer-heat, dryness, dampness, wind and fire all cause cough. ". The symptoms of cough are different due to different reasons, and the common cough is classified into persistent cough, spasmodic cough, dry cough, wet cough, allergic cough and the like.

The diagnosis of cough is mainly referred to as: (1) cough with voice or expectoration as main clinical symptoms; (2) acute cough, increased total peripheral blood leukocytes and neutrophil proportion; (3) cough due to exogenous pathogenic factors can be accompanied by exterior syndromes such as cold and heat; cough due to internal injury, which is caused by repeated attack of exogenous pathogens, has a long course of disease and is accompanied by asthma; (4) examining a lung X-ray photograph, wherein the normal or lung texture is thickened; (5) auscultation can be heard to increase the respiration in both lung fields, or accompanied by dry and wet rales.

At present, the cough treatment modes of traditional Chinese medicine and western medicine are different. The traditional Chinese medicine adopts a proper mode to treat according to the cause of cough, for example, lung-heat cough is treated by combining lung-moistening and cough-relieving medicines with heat-clearing and toxicity-removing medicines, for example, Victoria thermal sensation Sibetulin particles are used for relieving cough and reducing phlegm, clearing lung and moistening lung, and the effect of treating wind-heat cold cough and respiratory tract infection is excellent; western medicine treatment of cough mainly aims at diminishing inflammation, for example, antiviral drugs and antibiotics are used for treating cough caused by cold, for example, Fudosteine is used for treating cough with excessive phlegm in combination with amoxicillin. However, the cough is relieved to a certain extent by using a large amount of antibiotics, but the stress is brought to the health by increasing the drug resistance of bacteria, and the traditional Chinese medicine or the Chinese patent medicine has the characteristics of antibiosis, antivirus, immunity regulation, body function regulation, low side effect and the like, so that the prevention and treatment of cough by using the traditional Chinese medicine is an important direction in the future. Since cough is a common disease at present, there is a wide demand for such pharmaceutical preparations.

Through the above analysis, the problems and defects of the prior art are as follows: the use of antibiotics to treat cough and the increase of bacterial resistance puts pressure on the health of the body. Since antibiotic resistance is not a disease entity per se, and its invisible characteristics are not known, and the consequences of extended cough course, increased mortality and the like due to antibiotic resistance are often masked by various clinical syndromes of patients, there are various difficulties in detecting antibiotic resistance and overcoming bacterial resistance. When humans use antibiotics to kill bacteria, in some cases, these bacteria can respond by spontaneously mutated genes, which will alter their structure such that the antibiotic cannot kill them. The bacteria can then transmit these genes to other bacteria by simple mating (technically referred to as "conjugation"), and these resistant bacteria can spread from one organism to another. The most problematic part of this is that bacteria can share these genes with each other in bacterial populations, so that they can even transmit resistance without the need for genetic similarity. Because the body is filled with trillions of different types of bacteria, humans and animals can, in turn, transmit these drug-resistant bacteria to each other. Furthermore, in all these problems, it is most critical that we can spread those resistant bacteria to each other inside their own body. Thus, even if a human or animal has been exposed to antibiotics only once during life, they may contain easily transmitted variant bacteria. The use of antibiotics in large quantities leads to the rapid development of drug resistance by pathogens, which leads to the reduction of the immune system function of the body.

The traditional Chinese medicine composition is prepared by a traditional Chinese medicine processing technology and an ultramicro wall-breaking crushing technology and is applied by combining a modern extraction technology, so that the natural structure and the biological activity of the Chinese patent medicine are well kept, and the Chinese patent medicine composition has unique advantages in the aspects of immunization and virus resistance.

Disclosure of Invention

Aiming at the problems in the prior art, the invention provides a traditional Chinese medicine active ingredient composition for treating cough and a preparation method thereof.

The compound for treating the cough and other diseases caused by the cough is one or more of tormentic acid, alpha-cedrol, beta-sitosterol and ammonium glycyrrhizinate.

Furthermore, the stereoisomer, pharmaceutically acceptable salt, or pharmaceutically acceptable ester, amide, solvate or hydrate thereof of the compound for treating cough and diseases caused by cough can be used in the preparation of medicaments, and is characterized in that the medicaments are used for treating cough and other diseases caused by cough.

The invention also aims to provide a traditional Chinese medicine active ingredient composition for treating cough, which is prepared from the compounds for treating cough and other diseases caused by cough, and the traditional Chinese medicine active ingredient composition for treating cough comprises, by mass, 10-40 parts of tormentic acid, 10-30 parts of alpha-cedrol, 10-40 parts of beta-sitosterol and 15-30 parts of ammonium glycyrrhizinate.

Further, the traditional Chinese medicine active ingredient composition for treating cough comprises, by mass, 15-35 parts of tormentic acid, 15-25 parts of alpha-cedrol, 15-40 parts of beta-sitosterol and 18-25 parts of ammonium glycyrrhizinate.

Further, the traditional Chinese medicine active ingredient composition for treating cough comprises, by mass, 20-30 parts of tormentic acid, 18-25 parts of alpha-cedrol, 20-35 parts of beta-sitosterol and 20-25 parts of ammonium glycyrrhizinate.

Furthermore, the traditional Chinese medicine active ingredient composition for treating cough comprises, by mass, 25-28 parts of tormentic acid, 23-25 parts of alpha-cedrol, 25-30 parts of beta-sitosterol and 23-25 parts of ammonium glycyrrhizinate.

Another object of the present invention is to provide an application method of the traditional Chinese medicine active ingredient composition for treating cough in preparing a medicine for treating cough and respiratory diseases, wherein the cough and respiratory diseases comprise: persistent cough, dry cough, wet cough, and respiratory tract infections caused by cough, pneumonia, cough variant asthma, emphysema, and pleurisy.

Further, the cough comprises fever, pharynx itch, expectoration, chest distress, asthma; the respiratory tract infection is inflammation of the respiratory tract mucous membrane, chronic pharyngitis and chronic bronchitis; the pneumonia comprises hyperpyrexia, purulent phlegm, dyspnea, chest pain; the cough variant asthma comprises a stimulating dry cough; emphysema including debilitation, weight loss, anorexia, epigastric distention, and dyspnea; the pleurisy comprises chest pain, cough, chest distress, short breath and dyspnea.

Another object of the present invention is to provide a cough and respiratory disease treatment drug prepared from the cough and respiratory disease treatment traditional Chinese medicine active ingredient composition, wherein the cough and respiratory disease treatment drug comprises: the traditional Chinese medicine active ingredient composition for treating the cough is mixed with one or more pharmaceutically acceptable carriers or inert auxiliary materials; the pharmaceutically acceptable carrier or inert excipient comprises: diluent, excipient, filler, adhesive, wetting agent, disintegrating agent, absorption enhancer, surfactant, adsorption carrier, lubricant and correctant; the flavoring agent comprises flavoring agent and sweetener.

Further, the medicament for treating cough and respiratory diseases is a pharmaceutically acceptable dosage form; the pharmaceutically acceptable dosage forms are liquid preparations, granules, pills and tablets.

The preparation method of the medicine for treating cough and respiratory disease comprises the steps of preparing a liquid preparation of the medicine for treating cough and respiratory disease, preparing granules of the medicine for treating cough and respiratory disease, preparing pills of the medicine for treating cough and respiratory disease, and preparing tablets of the medicine for treating cough and respiratory disease.

Further, the extraction preparation of the relevant traditional Chinese medicine effective components comprises the following steps:

extracting tormentic acid:

1) quince seeds are taken as raw materials, ethanol solution is firstly used for extraction, after an extracting solution is concentrated, petroleum ether and trichloromethane are sequentially used for room-temperature extraction, after petroleum ether and trichloromethane fractions are removed, ethyl acetate is used for extraction, ethyl acetate is recovered from an extracting solution, the extracting solution is concentrated to be pasty, and a crude extract is obtained after drying; 2) eluting the crude extract with silica gel chromatographic column, wherein the eluent is a mixture of chloroform, methanol and water, and the crude extract is subjected to first preparative HPLC, then Sephadex LH-20 column chromatography and finally second preparative HPLC; the mobile phase of chromatography and HPLC are methanol solution, and the product with high purity can be obtained.

Extracting alpha-cedrol:

dried fine powder of badam was weighed, sieved through a 40 mesh sieve for standby, a funnel containing a certain amount of water was placed on a kirschner distillation head, 150mL of water and benzaldehyde were put into a distillation flask and placed on a heat source, and a condenser tube and a receiving flask were installed. The water and the badam fines in the flask were heated to boiling and water was gradually added from the separatory funnel as water vapor was distilled off along with the compounds. In the distillation process, the turbid liquid is condensed and accumulated in the receiving bottle along with hot steam, and when the distillation is finished, the distilled liquid is clarified from turbidity. The mixture vapor of the organic matter and water is condensed into emulsion through a condensing pipe and enters a receiver. And then placing the mixture of water and the organic matter in a separating funnel, taking the organic layer, and obtaining the product by a recrystallization method.

Extracting beta-sitosterol:

drying cucumber seeds, pulverizing, sieving with 40 mesh sieve, weighing 10.0g, placing in a round bottom flask, adding 75% ethanol 100ml, reflux-extracting in a Soxhlet reflux apparatus for 100min, reflux-extracting with 50ml 75% ethanol for 80min for the second time, and reflux-extracting with 50ml 75% ethanol for 60min for the third time. After the reflux is finished, combining reflux liquid for 3 times, performing reduced pressure evaporation on a rotary evaporator, recovering ethanol, adding ether into residues for dissolving, filtering, placing filtrate into a separating funnel, adding distilled water to enable the ether to be in a water saturated state, adding a 5% NaOH solution, shaking, standing for layering, repeating for three times, combining water solutions, adding hydrochloric acid to adjust the pH value to be about 3, adding water saturated ether for extraction for 3 times, and evaporating the solvent in a water bath to dryness to obtain a beta-sitosterol product.

Extracting ammonium glycyrrhetate:

drying Glycyrrhrizae radix, pulverizing, sieving with 40 mesh sieve, precisely weighing, placing in conical flask with plug, adding methanol 30ml, ultrasonic treating for 30min, filtering, treating residue once again by the same method, mixing filtrates, steaming to near dry, dissolving residue with appropriate amount of methanol, transferring to 50ml measuring flask, adding methanol to scale, shaking, filtering, collecting filtrate, treating with macroporous adsorbent resin, and evaporating under reduced pressure to dryness to obtain the final product.

Further, the preparation of the liquid preparation of the medicine for treating cough and respiratory diseases comprises the following steps:

weighing tormentic acid, alpha-cedrol, beta-sitosterol and ammonium glycyrrhizinate according to parts by weight, grinding into powder and mixing to obtain a traditional Chinese medicine active ingredient composition for treating cough; dissolving the Chinese medicinal active ingredient composition for treating cough in 10ml of filtered purified water to obtain a mixed solution; adding DMSO with one thousandth of the mass of the mixed solution into the mixed solution, vortexing for 3 minutes, and completely dissolving the mixture to obtain the medicine for treating cough and respiratory diseases.

Further, the preparation of the medicinal granule for treating cough and respiratory diseases comprises the following steps:

weighing tormentic acid, alpha-cedrol, beta-sitosterol and ammonium glycyrrhizinate according to parts by weight, grinding into powder and mixing to obtain a traditional Chinese medicine active ingredient composition for treating cough; adding maltodextrin, microcrystalline cellulose and talcum powder into the traditional Chinese medicine active ingredient composition for treating cough to obtain mixed powder; adding 5% starch slurry into the mixed powder to prepare soft material, and sieving the soft material to obtain wet granules; drying the wet granules to obtain the medicinal granules for treating cough and respiratory diseases.

Further, the preparation of the pharmaceutical tablet for treating cough and respiratory diseases comprises the following steps:

weighing tormentic acid, alpha-cedrol, beta-sitosterol and ammonium glycyrrhizinate according to parts by weight, grinding into powder and mixing to obtain a traditional Chinese medicine active ingredient composition for treating cough; adding a carrier or an excipient into the traditional Chinese medicine active ingredient composition for treating cough, performing wet granulation, tabletting and coating to obtain the medicinal tablet for treating cough and respiratory diseases.

Further, the preparation of the medicinal pill for treating cough and respiratory diseases comprises the following steps:

weighing tormentic acid, alpha-cedrol, beta-sitosterol and ammonium glycyrrhizinate according to parts by weight, grinding into powder and mixing to obtain a traditional Chinese medicine active ingredient composition for treating cough; adding carrier or excipient into the Chinese medicinal active ingredient composition for treating cough to obtain medicinal pill for treating cough and respiratory diseases.

By combining all the technical schemes, the invention has the advantages and positive effects that: the functional components of tormentic acid, alpha-cedrol, beta-sitosterol and ammonium glycyrrhizinate extracted from quince, badam, cucumber seed and liquorice in the thermal sensation salidroside granules are combined into a compound pharmaceutical composition, and when the compound pharmaceutical composition is prepared into a preparation, the total weight of the functional component groups used in the compound pharmaceutical composition is far lower than that of active components of a water decoction or an extract composition of the raw materials of the thermal sensation salidroside granules, so that great convenience is provided for preparing the preparation and applying the compound pharmaceutical composition. The raw materials are synergistically matched and enhanced, so that the traditional Chinese medicine composition has good effects of clearing heat, relieving inflammation and internal heat, dissipating blood stasis, relieving pain, relieving cough and relieving cough, fundamentally achieves the effects of eliminating dampness and eliminating phlegm, and has obvious treatment effects on dry cough, sore throat, bronchitis and the like, and has the advantages of quick response and small toxic and side effects.

The traditional Chinese medicine active ingredient composition provided by the invention has definite drug effect substance basis, is prepared from tormentic acid, alpha-cedrol, beta-sitosterol and ammonium glycyrrhetate, has definite structure, fixed components and controllable quality, and lays a foundation for the safety and effectiveness of the traditional Chinese medicine active ingredient composition; the action mechanism is clear: by adopting a mode of combining classical pharmacology and system biology research, pharmacodynamic research proves that the traditional Chinese medicine active ingredient composition can effectively reduce the release of cytokines and inflammatory mediators such as TNF-alpha, IL-6, IL-13, TLR2, IgE and the like in mouse serum, further relieve airway infectivity and allergic inflammatory reaction to reduce the high sensitivity of cough and reduce the stimulation to cough centers so as to achieve the aim of relieving cough.

Drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings needed to be used in the embodiments of the present application will be briefly described below, and it is obvious that the drawings described below are only some embodiments of the present application, and it is obvious for those skilled in the art that other drawings can be obtained from the drawings without creative efforts.

Fig. 1 is a schematic diagram showing comparison of cough latency after capsaicin atomization induced cough in 6 groups of mice provided by the embodiment of the invention.

Fig. 2 is a schematic diagram showing the comparison of cough frequency of 6 groups of mice after capsaicin atomization induced cough.

FIG. 3 is a graphical representation of the comparison of the cough suppressing rates of 4 groups of mice provided by the example of the present invention under different dosing conditions.

FIG. 4 is a schematic diagram showing comparison of inflammatory factors in serum of 6 groups of mice under different treatment modes.

FIG. 5 is a schematic diagram showing comparison of SOD and MDA levels of 6 groups of mice under different treatment modes.

FIG. 6 is a graph showing the comparative effect of SOD and MDA levels in different treatment modes of 6 groups of mice provided by the embodiment of the present invention.

FIG. 7 is a schematic diagram showing the comparison of sputum excretion of 6 groups of mice after cough induction by capsaicin atomization.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described below with reference to the following embodiments, which are not intended to limit the present invention.

Aiming at the problems in the prior art, the invention provides a traditional Chinese medicine active ingredient composition for treating cough and a preparation method thereof, and the invention is described in detail with reference to the accompanying drawings.

The compound for treating cough and other diseases caused by cough provided by the embodiment of the invention is selected from one or more of tormentic acid, alpha-cedrol, beta-sitosterol and ammonium glycyrrhizinate.

The invention provides a stereoisomer, pharmaceutically acceptable salt or pharmaceutically acceptable ester of a compound, or an amide or a solvate or hydrate thereof, a dispersible tablet, a film-coated tablet, a capsule, a dry suspension, a granule, a solid preparation, an injection, an external preparation, a spray, a liquid preparation or a compound preparation for treating cough and diseases caused by cough, and an application of the stereoisomer, pharmaceutically acceptable salt or pharmaceutically acceptable ester, amide or solvate of the compound in preparation of medicines, and is characterized in that the medicine is used for treating cough and other diseases caused by cough.

The traditional Chinese medicine active ingredient composition for treating cough provided by the embodiment of the invention comprises, by mass, 10-40 parts of tormentic acid, 10-30 parts of alpha-cedrol, 10-40 parts of beta-sitosterol and 15-30 parts of ammonium glycyrrhizinate.

The traditional Chinese medicine active ingredient composition for treating cough provided by the embodiment of the invention comprises, by mass, 15-35 parts of tormentic acid, 15-25 parts of alpha-cedrol, 15-40 parts of beta-sitosterol and 18-25 parts of ammonium glycyrrhizinate.

The traditional Chinese medicine active ingredient composition for treating cough provided by the embodiment of the invention comprises, by mass, 20-30 parts of tormentic acid, 18-25 parts of alpha-cedrol, 20-35 parts of beta-sitosterol and 20-25 parts of ammonium glycyrrhizinate.

The traditional Chinese medicine active ingredient composition for treating cough provided by the embodiment of the invention comprises, by mass, 25-28 parts of tormentic acid, 23-25 parts of alpha-cedrol, 25-30 parts of beta-sitosterol and 23-25 parts of ammonium glycyrrhizinate.

The cough and respiratory diseases provided by the embodiment of the invention comprise: persistent cough, dry cough, wet cough, and respiratory tract infections caused by cough, pneumonia, cough variant asthma, emphysema, and pleurisy.

The cough provided by the embodiment of the invention comprises fever, pharynx itch, expectoration, chest distress and asthma; the respiratory tract infection is inflammation of the respiratory tract mucous membrane, chronic pharyngitis and chronic bronchitis; the pneumonia comprises hyperpyrexia, purulent phlegm, dyspnea, chest pain; the cough variant asthma comprises a stimulating dry cough; emphysema including debilitation, weight loss, anorexia, epigastric distention, and dyspnea; the pleurisy comprises chest pain, cough, chest distress, short breath and dyspnea.

The medicine for treating cough and respiratory diseases provided by the embodiment of the invention comprises: the traditional Chinese medicine active ingredient composition for treating the cough is mixed with one or more pharmaceutically acceptable carriers or inert auxiliary materials; the pharmaceutically acceptable carrier or inert excipient comprises: diluent, excipient, filler, adhesive, wetting agent, disintegrating agent, absorption enhancer, surfactant, adsorption carrier, lubricant and correctant; the flavoring agent comprises flavoring agent and sweetener.

The medicament for treating cough and respiratory diseases provided by the embodiment of the invention is a pharmaceutically acceptable dosage form; the pharmaceutically acceptable dosage forms are liquid preparations, granules, pills and tablets.

The preparation method of the medicine for treating cough and respiratory disease provided by the embodiment of the invention comprises the steps of preparing a liquid preparation of the medicine for treating cough and respiratory disease, preparing granules of the medicine for treating cough and respiratory disease, preparing pills of the medicine for treating cough and respiratory disease, and preparing tablets of the medicine for treating cough and respiratory disease.

The preparation of the liquid pharmaceutical preparation for treating cough and respiratory diseases provided by the embodiment of the invention comprises the following steps:

The preparation of the drug granules for treating cough and respiratory diseases provided by the embodiment of the invention comprises the following steps:

The preparation of the pharmaceutical tablet for treating cough and respiratory diseases provided by the embodiment of the invention comprises the following steps:

The preparation method of the medicinal pill for treating cough and respiratory diseases provided by the embodiment of the invention comprises the following steps:

The present invention will be further described with reference to the following examples.

Example 1

Weighing 10mg of tormentic acid, 10mg of alpha-cedrol, 10mg of beta-sitosterol and 15mg of ammonium glycyrrhizinate, wherein the total weight is 45mg, grinding the materials into powder, mixing the powder, dissolving the powder in 10ml of filtered purified water, adding one thousandth of DMSO, and vortexing for 3 minutes to completely dissolve the mixture to obtain the composition.

Example 2

The composition is prepared from the following components: 15g of tormentic acid, 10g of alpha-cedrol, 10g of beta-sitosterol and 15g of ammonium glycyrrhizinate.

Mixing the above components, adding excipient or carrier, and making into granule.

The composition granule can be prepared by the following existing method:

weighing the raw materials of the composition, grinding the raw materials into powder, uniformly mixing the powder, adding a proper amount of maltodextrin, microcrystalline cellulose and talcum powder to obtain mixed powder, adding starch slurry with the volume fraction of 5% into the mixed powder to prepare a soft material, sieving the soft material to obtain wet granules, and finally drying the wet granules to obtain the granules of the composition.

Example 3

The traditional Chinese medicine active ingredient composition tablet is prepared from the following components: 30g of tormentic acid, 20g of alpha-cedrol, 20g of beta-sitosterol and 25g of ammonium glycyrrhizinate.

The composition tablets are prepared by taking the components, adding the carrier or excipient into the components according to the example 2, performing wet granulation, tabletting and coating.

Example 4

The composition pill is prepared from the following components: 28g of tormentic acid, 23g of alpha-cedrol, 25g of beta-sitosterol and 25g of ammonium glycyrrhizinate.

Mixing the above materials, adding carrier or excipient, and making into pill according to existing pill preparation method.

It should be noted that the preparation method of the composition dosage form is only exemplary and not limiting to the protection scope of the present invention, and for preparing the composition granule, pill or tablet, the technology commonly used in the field can also be adopted, which is not mentioned here.

Example 5

Pharmacological experiments were conducted with the composition prepared in example 1 to demonstrate the efficacy of the present invention in treating cough.

Balb/c mice, weighing 18-25g, shared 48 mice. The medicine is divided into a blank group, a model group, a thermal sensation rivastine particle group, a traditional Chinese medicine active ingredient composition low-dose group, a traditional Chinese medicine active ingredient composition medium-dose group and a traditional Chinese medicine active ingredient composition high-dose group at random, each group is 8, the five groups except the blank group are smoked during experiments, 0.4mg/ml LPS is dripped into the nose, 30mg/ml thyroxine is perfused into the stomach, after the model building is successful, the thermal sensation rivastine particle group and the traditional Chinese medicine active ingredient composition group are perfused with corresponding medicines, and the blank group and the model group are fed with normal saline.

1. Determination of cough sensitivity in mice

After 24h of the last administration, the mice were aerosolized with capsaicin as a cough-inducing solution for 3min, and the number of coughs in the mice was observed within 5 min.

2. Experiment of anti-inflammatory action

Collecting peripheral whole blood of each group by adopting an eyeball picking method, centrifuging for 10min at 4 ℃ at 4500r/min, taking supernatant as mouse serum, and measuring the horizontal content of TNF-alpha, IL-6, IL-13, TLR2, TGF-beta 1 and IgE in the mouse serum of each group by adopting an ELISA method.

3. Experiment of antioxidant action

Immediately taking out part of lung tissues after the eyeballs of each group of mice are completely bled, putting the lung tissues into a freezing tube for freezing at the temperature of minus 20 ℃, washing the lung tissues by precooled PBS buffer solution, taking part of the lung tissues for tissue homogenization, centrifuging at 5000rpm for 10min, taking supernatant, and detecting the level contents of SOD and MDA in the lung tissues of each group of mice by adopting an ELISA method.

4. Phlegm-eliminating action experiment

4.1 plotting of phenol Red Curve

Precisely weighing 0.010g of phenol red, placing the phenol red in a volumetric flask, adding 5% sodium bicarbonate solution to 100ml, respectively sucking 0.025, 0.075, 0.125, 0.175, 0.250, 1.250 and 2.500ml of the phenol red solution, placing the phenol red solution in a 25ml volumetric flask, diluting the phenol red solution to a scale with 5% sodium bicarbonate solution, shaking uniformly, placing the solution in a dark place for 30min, measuring the absorbance at 546nm of a 754-type ultraviolet visible spectrophotometer, and drawing a standard curve by taking the concentration as a horizontal coordinate and the absorbance as a vertical coordinate.

4.2 method of operation

The above experiments are grouped in accordance, after the last administration for 1h, the abdominal cavity is injected with 0.1ml/10g phenol red solution, the patient is killed after half an hour, tissues around the trachea are stripped, the thyroid cartilage is taken out to reach a section of trachea branched from the trachea, the thyroid cartilage is placed into a test tube containing physiological saline, 0.1mmol NaOH is added, the test tube is placed in a dark place for 30min, the absorbance is measured at 546nm of an ultraviolet visible spectrophotometer, and the phenol red content is calculated according to a standard curve prepared by 4.1.

5. Results

(1) Susceptibility to cough in mice

After capsaicin atomization is used for inducing cough, the cough latency of mice in the blank group is longer, the cough frequency is less, the cough latency of the mice in the model group and the mice in the administration group is shortened to different degrees, and the cough frequency is increased; compared with the model group, the mice of the positive drug group and the administration group have different degrees of prolongation and reduction of cough latency and cough frequency, and the difference has statistical significance (as shown in table 1, figure 2 and figure 3).

Table 1 effect of Chinese medicinal composition on capsaicin induced cough mouse (n ═ 8)

Note: p <0.05 compared to blank; p <0.05 compared to model group.

(2) Anti-inflammatory action

Compared with the blank group, the levels of TLR2, TNF-alpha, IL-6, IL-13 and IgE of the model group mice are obviously increased, and the levels of serum of the positive group mice and the administration group mice are slightly increased; however, the level of serum was reduced in both the positive and administered mice compared to the model group. The results show that the traditional Chinese medicine active ingredient composition can reduce the level content of IL-6, IL-13, TLR2, TNF-alpha and IgE in the serum of mice in a dose-dependent manner (as shown in figure 4).

(3) Antioxidation effect

Compared with the blank group, the SOD level content in the lung tissue of the mouse in the model group is obviously reduced, the MDA level is increased, the SOD level content in the positive group and the administration group is slightly reduced, and the MDA level is increased; compared with the model group, the positive group and the administration group have higher SOD level and lower MDA level. The results show that: the composition can effectively increase SOD level in mouse lung tissue, and reduce MDA level in mouse lung tissue (shown in figure 5 and figure 6).

(4) Action of eliminating phlegm

Compared with a model group, the traditional Chinese medicine active ingredient composition group and the positive control group can both obviously increase the mouse tracheal phenol red excretion amount, and along with the increase of the dosage of the composition, the mouse tracheal phenol red excretion amount is increased, the phlegm eliminating effect is more obvious, and the dosage-effect relationship is formed; compared with the positive control, the expectorant effect of the high-dose Chinese medicinal active ingredient composition group is more obvious (as shown in figure 7).

The above description is only for the purpose of illustrating the present invention and the appended claims are not to be construed as limiting the scope of the invention, which is intended to cover all modifications, equivalents and improvements that are within the spirit and scope of the invention as defined by the appended claims.

Claims

1. A compound for treating cough and other diseases caused by cough, which is characterized in that the compound for treating cough and other diseases caused by cough is selected from one or more of tormentic acid, alpha-cedrol, beta-sitosterol and ammonium glycyrrhizinate.

2. The compound for treating cough and cough-related diseases according to claim 1, wherein the compound for treating cough and cough-related diseases is a stereoisomer, a pharmaceutically acceptable salt or a pharmaceutically acceptable ester of the compound, or an amide or a solvate or a hydrate thereof, a dispersible tablet, a film-coated tablet, a capsule, a dry suspension, a granule, a solid preparation, an injection, an external preparation, a spray, a liquid preparation or a compound preparation, and is used for preparing a medicament for treating cough and other cough-related diseases.

3. The cough treatment traditional Chinese medicine active ingredient composition of the compound for treating cough and other diseases caused by cough according to claims 1-2 is characterized by comprising, by mass, 10-40 parts of tormentic acid, 10-30 parts of alpha-cedrol, 10-40 parts of beta-sitosterol and 15-30 parts of ammonium glycyrrhizinate.

4. The traditional Chinese medicine active ingredient composition for treating cough according to claim 3, which is composed of, by mass, 15-35 parts of tormentic acid, 15-25 parts of alpha-cedrol, 15-40 parts of beta-sitosterol and 18-25 parts of ammonium glycyrrhizinate.

5. The traditional Chinese medicine active ingredient composition for treating cough according to claim 3, which is composed of, by mass, 20-30 parts of tormentic acid, 18-25 parts of alpha-cedrol, 20-35 parts of beta-sitosterol and 20-25 parts of ammonium glycyrrhizinate.

6. The traditional Chinese medicine active ingredient composition for treating cough according to claim 3, which comprises, by mass, 25-28 parts of tormentic acid, 23-25 parts of alpha-cedrol, 25-30 parts of beta-sitosterol and 23-25 parts of ammonium glycyrrhizinate.

7. An application method of the traditional Chinese medicine active ingredient composition for treating cough according to any one of claims 3 to 6 in preparation of a medicine for treating cough and respiratory diseases, wherein the cough and the respiratory diseases comprise: persistent cough, dry cough, wet cough, and respiratory tract infections caused by cough, pneumonia, cough variant asthma, emphysema, and pleurisy.

8. The method for using the combination of active ingredients of traditional Chinese medicine for treating cough according to claim 7, wherein the cough includes fever, throat itching, expectoration, chest distress, asthma; the respiratory tract infection is inflammation of the respiratory tract mucous membrane, chronic pharyngitis and chronic bronchitis; the pneumonia comprises hyperpyrexia, purulent phlegm, dyspnea, chest pain; the cough variant asthma comprises a stimulating dry cough; emphysema including debilitation, weight loss, anorexia, epigastric distention, and dyspnea; the pleurisy comprises chest pain, cough, chest distress, short breath and dyspnea.

9. A medicine for treating cough and respiratory diseases, which is prepared by applying the traditional Chinese medicine active ingredient composition for treating cough according to any one of claims 3 to 6, is characterized by comprising the following components in parts by weight: the traditional Chinese medicine active ingredient composition for treating the cough is mixed with one or more pharmaceutically acceptable carriers or inert auxiliary materials; the pharmaceutically acceptable carrier or inert excipient comprises: diluent, excipient, filler, adhesive, wetting agent, disintegrating agent, absorption enhancer, surfactant, adsorption carrier, lubricant and correctant; the flavoring agent comprises flavoring agent and sweetener;

the medicament for treating cough and respiratory diseases is a pharmaceutically acceptable dosage form; the pharmaceutically acceptable dosage forms are liquid preparations, granules, pills and tablets.

10. The preparation method of the cough and respiratory disease treatment drug according to claim 9, wherein the preparation method of the cough and respiratory disease treatment drug comprises the steps of preparing a liquid cough and respiratory disease treatment drug preparation, preparing cough and respiratory disease treatment drug granules, preparing cough and respiratory disease treatment drug pills, and preparing cough and respiratory disease treatment drug tablets;

the preparation of the liquid preparation of the medicine for treating cough and respiratory diseases comprises the following steps:

weighing tormentic acid, alpha-cedrol, beta-sitosterol and ammonium glycyrrhizinate according to parts by weight, grinding into powder and mixing to obtain a traditional Chinese medicine active ingredient composition for treating cough; dissolving the Chinese medicinal active ingredient composition for treating cough in 10ml of filtered purified water to obtain a mixed solution; adding DMSO with one thousandth of the mass of the mixed solution into the mixed solution, vortexing for 3 minutes, and completely dissolving the mixture to obtain the medicine for treating cough and respiratory diseases;

the preparation of the medicinal granules for treating cough and respiratory diseases comprises the following steps:

weighing tormentic acid, alpha-cedrol, beta-sitosterol and ammonium glycyrrhizinate according to parts by weight, grinding into powder and mixing to obtain a traditional Chinese medicine active ingredient composition for treating cough; adding maltodextrin, microcrystalline cellulose and talcum powder into the traditional Chinese medicine active ingredient composition for treating cough to obtain mixed powder; adding 5% starch slurry into the mixed powder to prepare soft material, and sieving the soft material to obtain wet granules; drying the wet granules to obtain medicinal granules for treating cough and respiratory diseases;

the preparation of the medicine tablet for treating cough and respiratory diseases comprises the following steps:

weighing tormentic acid, alpha-cedrol, beta-sitosterol and ammonium glycyrrhizinate according to parts by weight, grinding into powder and mixing to obtain a traditional Chinese medicine active ingredient composition for treating cough; adding a carrier or an excipient into the traditional Chinese medicine active ingredient composition for treating cough, and performing wet granulation and tabletting coating to obtain a medicinal tablet for treating cough and respiratory diseases;

the preparation of the medicinal pill for treating cough and respiratory diseases comprises the following steps: