Traditional Chinese medicine composition for tonifying qi, dispelling wind, moistening lung and relieving cough, preparation, preparation method and application

Abstract

The invention relates to a traditional Chinese medicine composition for tonifying qi, dispelling wind, moistening lung and relieving cough, a preparation method and application. The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 9-15 parts of radix pseudostellariae, 5-9 parts of perilla leaves, 4-8 parts of platycodon grandiflorum, 5-8 parts of fried semen armeniacae amarae, 6-10 parts of uncaria rhynchophylla, 6-10 parts of fried rhizoma atractylodis macrocephalae, 6-10 parts of honey-fried radix asteris and 2-6 parts of honey-fried licorice roots. The traditional Chinese medicine composition is reasonable in formula, safe, effective, simple in process route and suitable for industrial production.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and in particular to a traditional Chinese medicine composition and preparation for invigorating qi, dispersing wind, moistening lungs and relieving cough, as well as a preparation method and application thereof. Background Art

[0002] Post-infectious cough (PIC) refers to a disease in which the cough persists after the acute symptoms of respiratory infection disappear, usually lasting 3 to 8 weeks. The clinical manifestations are irritating dry cough or coughing up a small amount of white mucus sputum, and no abnormalities in chest X-ray examination. Although the "Guidelines for the Diagnosis and Treatment of Cough (2021)" point out that PIC is often self-limiting and can usually be relieved on its own, some patients have stubborn coughs and even develop chronic coughs. In addition, in recent years, the incidence of PIC has been increasing, seriously interfering with patients' normal work, life and study. At present, the pathogenesis of post-infectious cough has not been thoroughly studied. Some believe that it is related to the release of inflammatory mediators, while others believe that it is related to the increased sensitivity of cough receptors. Western medicine mainly treats symptoms to relieve symptoms. At present, central antitussive drugs, oral or nebulized hormones, antihistamine receptor antagonists, compound preparations, etc. are mainly used, but the following problems still exist:

[0003] 1. Lack of specific therapeutic drugs for PIC;

[0004] 2. Extensive use of antibiotics leads to abuse;

[0005] 3. There is a lack of effective and safe treatment options, and there is a risk of excessive side effects from drugs. Summary of the invention

[0006] To solve any of the above technical problems, the purpose of the present invention is to provide a Chinese medicine composition and preparation for invigorating qi, soothing wind, moistening the lungs and relieving cough, as well as a preparation method and application.

[0007] To achieve the above object, the present invention adopts the following technical solutions:

[0008] One of the purposes of the present invention:

[0009] A traditional Chinese medicine composition for invigorating qi, dispersing wind, moistening lungs and relieving cough, comprising the following raw materials in parts by weight:

[0010] 9-15 parts of Pseudostellariae Radix, 5-9 parts of Perilla Leaves, 4-8 parts of Platycodon Grandiflorum, 5-8 parts of stir-fried bitter almonds, 6-10 parts of Uncaria rhynchophylla, 6-10 parts of stir-fried Atractylodes macrocephala, 6-10 parts of honey Aster, and 2-6 parts of roasted Licorice root.

[0011] As a further improvement of the present invention, the Chinese medicine composition is composed of the following raw materials in parts by weight: 9-11 parts of Pseudostellariae Radix, 6-8 parts of Perilla Leaves, 5-7 parts of Platycodon Grandiflorum, 5-7 parts of stir-fried bitter almonds, 7-9 parts of Uncaria rhynchophylla, 7-9 parts of stir-fried Atractylodes macrocephala, 7-9 parts of Aster tataricus, and 3-5 parts of roasted Licorice root.

[0012] As a further improvement of the present invention, the Chinese medicine composition is composed of the following raw materials in parts by weight: 12 parts of Pseudostellariae Radix, 7 parts of Perilla Leaves, 7 parts of Platycodon Grandiflorum, 7 parts of stir-fried bitter almonds, 10 parts of Uncaria rhynchophylla, 10 parts of stir-fried Atractylodes macrocephala, 10 parts of Aster tataricus, and 5 parts of roasted Licorice root.

[0013] As a further improvement of the present invention, the Chinese medicine composition is composed of the following raw materials in parts by weight: 10 parts of Pseudostellariae Radix, 6 parts of Perilla Leaves, 6 parts of Platycodon Grandiflorum, 6 parts of stir-fried bitter almonds, 8 parts of Uncaria rhynchophylla, 8 parts of stir-fried Atractylodes macrocephala, 8 parts of Aster tataricus, and 4 parts of roasted Licorice root.

[0014] The second purpose of the present invention is:

[0015] The preparation method of the Chinese medicine composition for invigorating qi, dispersing wind, moistening lungs and relieving cough comprises the following steps in sequence:

[0016] Step S1, weighing raw medicinal materials according to the weight ratio;

[0017] Step S2, boiling the raw medicinal materials with water for 1 to 3 times, and filtering the decoction;

[0018] Step S3, concentrating the extract to an extract concentrate having a relative density of 1.20 to 1.30 at 50° C. to 90° C.;

[0019] Step S4, drying the extracted concentrated liquid.

[0020] As a further improvement of the present invention, in step S2, take medicinal materials other than Uncaria rhynchophylla, add 8 times the amount of water, decoct twice, each time for 1 hour, and filter the decoction; add Uncaria rhynchophylla to the medicinal residue, add 8 times the amount of water, decoct once, each time for 0.5 hour.

[0021] As a further improvement of the present invention, in step S3, in step S4, when the drying method is reduced pressure drying, the temperature of reduced pressure drying is 50°C to 80°C, and the negative pressure is 0.06 to -0.1 MPa;

[0022] or,

[0023] In step S4, when the drying method is spray drying, 15% dextrin is added to the extraction concentrate for spray drying.

[0024] The third object of the present invention:

[0025] Provided is a Chinese medicine preparation of a Chinese medicine composition for invigorating qi, dispersing wind, moistening the lungs and relieving cough. The preparation is in the form of granules, tablets, capsules, oral liquid preparations or pills.

[0026] The fourth object of the present invention:

[0027] Provided is a method for preparing a Chinese medicine preparation of a Chinese medicine composition for invigorating qi, dispersing wind, moistening the lungs and relieving cough, the preparation method comprising the following steps:

[0028] Step S1, weighing raw medicinal materials according to the weight ratio;

[0029] Step S2, boiling the raw medicinal materials with water for 1 to 3 times, and filtering the decoction;

[0030] Step S3, concentrating the extract to an extract concentrate having a relative density of 1.20 to 1.30 at 50° C. to 90° C.;

[0031] Step S4, drying the extracted concentrated liquid to obtain a dry paste;

[0032] Step S5: After the dry paste is crushed, auxiliary materials are added and granulated to prepare a preparation.

[0033] As a further improvement of the present invention, in step S2, take the medicinal materials other than Uncaria rhynchophylla, add 8 times the amount of water, decoct twice, each time for 1 hour, and filter the decoction; add Uncaria rhynchophylla to the medicinal residue, add 8 times the amount of water, decoct once, each time for 0.5 hour;

[0034] In step S4, when the drying method is reduced pressure drying, the temperature of reduced pressure drying is 50° C. to 80° C., and the negative pressure is 0.06 to -0.1 MPa;

[0035] or,

[0036] In step S4, when the drying method is spray drying, 15% dextrin is added to the extraction concentrate for spray drying.

[0037] As a further improvement of the present invention,

[0038] In step S5, the granulation method is dry granulation, the auxiliary material is a combination of one or more of soluble starch, dextrin, and microcrystalline cellulose; the sweetener is a combination of one or more of sucralose, steviol glycoside, and aspartame;

[0039] or,

[0040] In step S5, the granulation method is to add filler and 0.2% sucralose according to the ratio of dry paste powder to filler of 1:0.75 for wet granulation; wherein the ratio of the filler is dextrin: soluble starch = 1:4.

[0041] The fifth object of the present invention:

[0042] A Chinese medicine composition for invigorating qi, dispersing wind, moistening the lungs and relieving cough is used in the preparation of medicine for treating and / or preventing post-infectious cough.

[0043] According to traditional Chinese medicine, the causes of post-infection cough include pathogenic wind, insufficient qi and yin, visceral disorders, insufficient righteousness, etc., and are closely related to the six evil qi, especially wind evil. Wind evil is the initiating factor of cough and runs through the entire process of cough. External wind invades, thus affecting the lung's function of spreading and descending. Disorders in the function of spreading and descending can cause lung qi to rise and cause cough. In addition to external wind causing cough, internal wind should not be ignored. Internal wind mainly refers to liver wind. The liver belongs to wood in the five elements and governs wind. Factors that cause wood qi to fail can induce liver wind, including liver yang turning into wind, yin and blood deficiency inducing liver wind, etc. Because the liver and lung meridians are connected, as stated in "Lingshu·Jingmai": "The liver foot Jueyin meridian starts at the tuft of hair on the thumb... reaches the lower abdomen, hugs the stomach, belongs to the liver and connects to the gallbladder... Its branches go through the diaphragm from the liver and flow up to the lungs." Therefore, liver wind can easily invade the lungs, affecting the lung's qi and causing cough; in addition, the liver and lungs are related to each other in ascending and descending, as stated in Suwen·Cijinlun: "The liver is born on the left, and the lungs are hidden on the right." The liver is responsible for growth and the lungs are responsible for descending. If the liver wood is depressed and the liver qi does not rise, the lung's descending function will be blocked, affecting the lung's function of spreading and spreading. The lung's descending function is abnormal and causes cough. The course of PIC is usually long. Long-term coughing not only damages the lung qi, but also consumes the lung yin. If the qi and yin are insufficient, consider replenishing qi and nourishing yin. In addition, dysfunction of other organs can also affect the descending of lung qi, especially the three organs with the closest relationship to the lung, spleen, and liver.

[0044] Therefore, according to the technical scheme of the present invention, the pharmaceutical composition provided by the present invention is scientifically formulated by the medicinal flavors such as Radix Pseudostellariae, Folium Perillae, Platycodon grandiflorum, Stir-fried Bitter Almonds, Rhizoma Uncariae, Aster tataricus, and Radix Glycyrrhizae, and has a good therapeutic effect on post-infection cough (Syndrome of Lung Deficiency and Wind Excessiveness); for the key pathogenesis of "lung and spleen deficiency, wind-excessive contracture, and disorder of descending and descending", Radix Pseudostellariae is used to invigorate qi, and Folium Perillae is used to dredge the surface; Platycodon grandiflorum is used to dredge the lungs, and Stir-fried Bitter Almonds are used to descend qi; Rhizoma Uncariae dispels wind, helps Folium Perillae to dredge the surface, stir-fried Atractylodes macrocephala strengthens the spleen and resolves phlegm, helps Radix Pseudostellariae to invigorate qi, and Aster tataricus is used to moisten the lungs, and helps the function of delicate organs to be repaired; Radix Glycyrrhizae is used to invigorate qi and harmonize the middle, resolves phlegm and relieves cough, and harmonizes various medicines. The whole prescription is used for invigorating and dredging, descending and regulating, and drying and moistening are applied together, and the effects of invigorating qi and dispersing wind, moistening the lungs and relieving cough are played together. The pharmaceutical composition provided by the present invention makes good use of Rhizoma Uncariae, and it is contained in "New Compilation of Materia Medica": "Rhizoma Uncariae removes wind very quickly, and those with wind disease must use it". "Medicine has the magic of getting along with others." According to different cough syndromes, Uncaria rhynchophylla is combined with wind-dispelling, phlegm-resolving, dryness-moistening, qi-regulating and cough-relieving medicines respectively, fully following the idea of ​​TCM's syndrome differentiation and treatment.

[0045] The traditional Chinese medicine composition of the invention has a reasonable formula, is safe and effective, has a simple preparation process route, and is suitable for industrial production.

[0046] The above description is only an overview of the technical solution of the present invention. In order to more clearly understand the technical means of the present invention and implement it according to the contents of the specification, the following are preferred embodiments of the present invention. DETAILED DESCRIPTION

[0047] The following examples are used to illustrate the present invention, but are not intended to limit the scope of the present invention.

[0048] In order to make those skilled in the art better understand the scheme of the present invention, the technical scheme in the embodiment of the present invention will be clearly and completely described below in conjunction with the embodiment of the present invention. Obviously, the described embodiment is only a part of the embodiment of the present invention, rather than all the embodiments. The components of the embodiment of the present invention generally shown here can be arranged and designed in various configurations. Therefore, the following detailed description of the embodiment of the present invention is not intended to limit the scope of the invention claimed for protection, but merely represents the selected embodiment of the present invention. Based on the embodiment of the present invention, all other embodiments obtained by those skilled in the art without making creative work belong to the scope of protection of the present invention.

[0049] If no specific conditions are specified in the examples of the present application, the experiments are carried out under conventional conditions. The raw materials or excipients used, as well as the reagents or instruments used without indicating the manufacturer, are all conventional products that can be obtained through commercial purchase. The raw materials used all comply with the provisions of the inspection items of various medicinal materials in the Chinese Pharmacopoeia, and the excipients comply with the requirements of Part IV of the Chinese Pharmacopoeia or the standards for the use of food additives.

[0050] Example:

[0051] Example 1 Preparation of Chinese medicine combination:

[0052] According to the formula, 100g of Radix Pseudostellariae Radix, 60g of Perilla Leaf, 60g of Platycodon Grandiflorum, 60g of Stir-fried Apricot Kernel, 80g of Uncaria Rhizoma, 80g of Stir-fried Atractylodes Macrocephala, 80g of Honey Aster, and 40g of Radix Glycyrrhizae Radix were weighed; the medicinal flavors except Uncaria Rhizoma were taken, 8 times of water were added, and the mixture was extracted twice, each time for 1 hour, filtered, Uncaria Rhizoma was added to the residue, and 8 times of water was added again, and the mixture was extracted once, and the extraction time was 0.5 hour; the mixture was concentrated under reduced pressure at 50℃~90℃ to a relative density of 1.20~1.30; the extracted concentrated solution was dried under reduced pressure at a drying temperature of 50℃~80℃; after drying, the dry paste powder was obtained by crushing. The filler (dextrin: soluble starch = 1:4) and 0.2% sucralose were added according to the ratio of dry paste powder to filler of 1:0.75 for wet granulation to prepare granules.

[0053] Example 2 Preparation of Chinese medicine combination:

[0054] According to the formula, 100g of Radix Pseudostellariae Radix, 60g of Perilla Leaf, 60g of Platycodon Grandiflorum, 60g of Stir-fried Apricot Kernel, 80g of Uncaria Rhizoma, 80g of Stir-fried Atractylodes Macrocephala, 80g of Honey Aster, and 40g of Rhizoma Licorice are weighed; the medicinal flavors except Uncaria Rhizoma are taken, 8 times the amount of water is added, and the extraction is performed twice, each time for 1 hour, and filtered; Uncaria Rhizoma is added to the medicinal residue, and 8 times the amount of water is added again, and the extraction is performed once, and the extraction time is 0.5 hour; the mixture is concentrated under reduced pressure at 50℃~90℃ to a relative density of 1.20~1.30; 15% of dextrin is added to the extract concentrate for spray drying; after drying, the dry paste powder is obtained by crushing. An appropriate amount of diluent, sweetener, and lubricant are added to the dry paste powder, and dry granulation is performed to prepare granules.

[0055] Example 3 Preparation of Chinese medicine combination:

[0056] According to the formula, 100g of Radix Pseudostellariae Radix, 60g of Perilla Leaf, 60g of Platycodon Grandiflorum, 60g of Stir-fried Apricot Kernel, 80g of Uncaria Rhizoma, 80g of Stir-fried Atractylodes Macrocephala, 80g of Honey Aster, and 40g of Rhizoma Licorice are weighed; the medicinal flavors except Uncaria Rhizoma are taken, 8 times the amount of water is added, extracted twice, each time for 1 hour, filtered, Uncaria Rhizoma is added to the medicinal residue, 8 times the amount of water is added again, extracted once, and the extraction time is 0.5 hour; concentrated under reduced pressure at 50℃~90℃ to a relative density of 1.20~1.30; the extracted concentrated solution is dried under reduced pressure at a drying temperature of 50℃~80℃; after drying, the dry paste powder is obtained by crushing. An appropriate amount of diluent, sweetener, and lubricant are added to the dry paste powder, and dry granulation is performed to prepare granules.

[0057] Example 4 Preparation of Chinese medicine composition:

[0058] According to the formula, 120g of Radix Pseudostellariae Radix, 70g of Perilla Leaf, 70g of Platycodon Grandiflorum, 70g of Stir-fried Apricot Kernel, 100g of Uncaria Rhizoma, 100g of Stir-fried Atractylodes Macrocephala, 100g of Honey Aster, and 50g of Radix Glycyrrhizae Radix were weighed, and the medicinal flavors except Uncaria Rhizoma were taken, and 8 times of water was added, and the extracts were extracted twice, each for 1 hour, filtered, and Uncaria Rhizoma was added to the residues, and 8 times of water was added again, and the extracts were extracted once, and the extraction time was 0.5 hours; the extract was concentrated under reduced pressure at 50℃~90℃ to a relative density of 1.20~1.30; the extract concentrate was dried under reduced pressure at a drying temperature of 50℃~80℃; after drying, the dry paste powder was obtained by crushing. An appropriate amount of diluent, sweetener, and lubricant were added to the dry paste powder, and dry granulation was performed to prepare granules.

[0059] Example 5 Preparation of Chinese medicine composition:

[0060] According to the formula, 100g of Radix Pseudostellariae Radix, 60g of Perilla Leaf, 60g of Platycodon Grandiflorum, 60g of Stir-fried Apricot Kernel, 80g of Uncaria Rhizoma, 80g of Stir-fried Atractylodes Macrocephala, 80g of Honey Aster, and 40g of Rhizoma Licorice are weighed, and the medicinal flavors except Uncaria Rhizoma are taken, 8 times the amount of water is added, and the extract is extracted twice, each time for 1 hour, filtered, Uncaria Rhizoma is added to the residue, and 8 times the amount of water is added again, and the extract is extracted once, and the extraction time is 0.5 hour; the extract is concentrated under reduced pressure at 50℃~90℃ to a relative density of 1.20~1.30; the extract concentrate is taken for vacuum drying at a drying temperature of 50℃~80℃; after drying, the dry paste powder is obtained by crushing. An appropriate amount of diluent, sweetener, and lubricant are added to the dry paste powder, and dry granulation is performed to prepare granules.

[0061] Experimental example:

[0062] Experimental Example 1 Screening test of extraction process of Chinese medicine composition

[0063] 1. Weigh the raw materials.

[0064] According to the recipe, weigh 100g of Pseudostellaria heterophylla, 60g of Perilla leaf, 60g of Platycodon grandiflorum, 60g of stir-fried bitter almond, 80g of Uncaria rhynchophylla, 80g of stir-fried Atractylodes macrocephala, 80g of honey Aster, and 40g of roasted Licorice root.

[0065] 2. Research on extraction process.

[0066] 2.1 Orthogonal experimental design

[0067] The water addition times, extraction time and extraction times were used as the investigation factors, and each factor was set at three levels. 4 ) orthogonal table was used for the experiment, and the comprehensive scores of index component transfer rate and dry paste rate were used as indicators. Range and multi-factor variance analysis were used for data statistics to optimize the extraction process conditions.

[0068] Table 1 Orthogonal factor level table

[0069]

[0070] Table 2 Orthogonal test design and results

[0071] Test No. A (add water multiple times) B(Number of extractions) C(Extraction time) D(blank) Overall Rating 1 6 1 0.5 1 44.7 2 6 2 1 2 85.2 3 6 3 1.5 3 94.3 4 8 1 1 3 59.3 5 8 2 1.5 1 86.5 6 8 3 0.5 2 94.0 7 10 1 1.5 2 65.0 8 10 2 0.5 3 77.8 9 10 3 1 1 98.2 <![CDATA[k1]]> 74.7 56.3 72.2 76.5 <![CDATA[k2]]> 79.9 83.2 80.9 81.4 <![CDATA[k3]]> 80.3 95.5 81.9 77.1 R 5.6 39.2 9.8 4.9

[0072] Table 3 Results of variance analysis

[0073] Sources of variance Sum of Squared Deviations Degrees of Freedom F Ratio P Significance A. Add water times 58.560 2 1.362 0.423 Not significant B Extraction times 2406.167 2 55.975 0.018 * C extraction time 172.727 2 4.018 0.199 Not significant Residual 42.987 2

[0074] Note: *P<0.05, **P<0.01.

[0075] As shown in Tables 2 and 3, intuitive analysis and variance analysis show that the influence of the three extraction factors on the comprehensive score is: factor B (number of extractions) > factor C (extraction time) > factor A (water addition times), and the optimal level is A3B3C3, among which factor B (number of extractions) has a significant effect on the comprehensive score, and factor A (water addition times) and factor C (extraction time) have no significant effect. The k values ​​at each level of comprehensive factors A and C are equivalent to A2 and A3, and C2 and C3. The selected extraction process is to add 8 times the amount of water, extract 3 times, and the extraction time is 1 hour.

[0076] 2.2 Extraction process optimization.

[0077] Considering that Uncaria rhynchophylla is sweet and bitter, slightly cold, and has a short decoction time, it is used clinically for its light taste. Comparison process: Uncaria rhynchophylla is added during the third decoction, 8 times the amount of water is added, and extraction is performed 3 times, with extraction times of 1 hour, 1 hour, and 0.5 hours respectively; the result is the same as the optimal process of (2). The results in Table 4 show that the comprehensive scores of the two extraction processes are equivalent, so the extraction process is selected: take the medicinal flavor except Uncaria rhynchophylla, add 8 times the amount of water, extract twice, each time for 1 hour, filter, add Uncaria rhynchophylla to the residue, add 8 times the amount of water, extract once, and the extraction time is 0.5 hour.

[0078] Table 4 Comparison of extraction processes

[0079] serial number Overall Rating 1 96.0 2 95.8

[0080] 3. Concentration of the extract. The extract is concentrated under reduced pressure at a temperature of 50°C-90°C and a negative pressure of 0.06 to -0.1 MPa to a relative density of d = 1.20 to 1.30.

[0081] 4. Drying under reduced pressure. Take the extract concentrate and dry it under reduced pressure at a temperature of 50°C to 80°C and a negative pressure of 0.06 to -0.1 MPa. After drying, crush it to obtain dry paste powder.

[0082] 5. Dry granulation: Add appropriate amount of diluent, sweetener and lubricant to the dry paste powder, and carry out dry granulation under certain feeding and granulation process conditions.

[0083] 6. Inner and outer packaging: The above particles are inner packaged according to the quantitative quantity, and outer packaged according to the sample box, finished product inspection and storage.

[0084] Specifically, the auxiliary material added in the above dry granulation is selected from one or more of soluble starch, dextrin, and microcrystalline cellulose, preferably soluble starch.

[0085] Specifically, the sweetener added in the dry granulation is selected from one or more of sucralose, stevioside, and aspartame, preferably sucralose.

[0086] Experimental Example 2 Study on the Preparation and Drying Process of Traditional Chinese Medicine Composition

[0087] In addition to the reduced pressure drying process in Experimental Example 1, the present invention also adopts a spray drying method. Although spray drying has the advantages of short drying time, uniform particle size, and high work efficiency. However, the product formula is mostly traditional Chinese medicine. The dry extract obtained after extraction and concentration by conventional methods has a large viscosity. After drying, it is easy to stick to the plate and hang on the wall, resulting in a large loss. It has been found through experiments that adding an appropriate amount of dextrin to the concentrated solution can effectively reduce the viscosity of the spray-dried powder, increase the yield of the spray-dried powder, and ensure the fine powder state, which is more conducive to granulation. The research data is as follows.

[0088] Powder yield = (weight of dry powder - amount of dextrin added) / total weight of concentrate

[0089] Table 5 Comparison of extraction processes

[0090] Dextrin addition% Material properties Fine powder moisture % Flour yield% 7 Dry powder, slightly sticky 6.1 17.5 10 Dry powder, good dispersibility 4.9 20.3 15 Dry powder, good dispersibility 4.6 21.6

[0091] From the results in Table 5, it can be seen that when the amount of dextrin added is 15%, the powder obtained by drying has good dispersibility and a high powder yield, so 15% dextrin is added to the concentrated solution for spray drying.

[0092] Experimental Example 3: Study on the granulation process of Chinese medicine composition

[0093] In addition to the dry granulation in Experimental Example 1, the present invention also adopts wet granulation.

[0094] 1. Selection of filler type and dosage

[0095] Wet granulation was carried out according to the single factor experimental design in Table 6. Different proportions of dextrin, soluble starch and sucrose powder were used as fillers for granulation. The filler and dosage were selected based on the soft material state, granulation phenomenon, solubility and forming rate. The results are shown in Table 6.

[0096] Table 6 Results of investigation on different filler types and proportions

[0097]

[0098]

[0099] From Table 6, we know that when the amount of filler is 0.5 to 1 times of the dry paste powder, dextrin is used as filler, the soft material prepared is non-sticky and has a large amount of fine powder; soluble starch is used as filler, the soft material prepared is sticky and has a sticky phenomenon; sucrose powder is used as filler, the soft material prepared is sticky and easy to agglomerate, but easy to disperse after drying, but sucrose powder will limit the number of people who can use it. Therefore, dextrin and soluble starch are selected as fillers for Shensu cough granules, and the amount is about 0.5 to 0.75 times of the dry paste powder.

[0100] 2. Selection of filler ratio

[0101] According to Table 7, mixtures of dextrin and soluble starch in different proportions were used as fillers. The ratio of dry paste powder to filler was 1:0.75, mixed and granulated. The filler ratio was selected based on the soft material state, granulation phenomenon, solubility and molding rate. The results are shown in Table 7.

[0102] Table 7 Granulation results of different proportions of fillers

[0103] Excipient ratio Soft material status Granulation phenomenon Solubility Forming rate (%) Dextrin: soluble starch = 1:1 It is not easy to form a ball when holding it in hand Easy to sift, more powder qualified 92.9 Dextrin: soluble starch = 1:2 It is not easy to form a ball when holding it in hand Easy to sift, more powder qualified 94.1 Dextrin: soluble starch = 1:3 Less likely to form a ball when held in the hand Easier to sieve qualified 94.5 Dextrin: soluble starch = 1:4 Gathered in hand, easily dispersed when touched Easier to sieve qualified 95.2

[0104] As shown in Table 7, as the proportion of soluble starch in the filler increases, the particle forming rate increases from 92.9% to 95.2%, so the filler ratio is selected as dextrin: soluble starch = 1:4.

[0105] 3. Selection of flavoring agent type and dosage

[0106] 20 professional technicians were selected to independently evaluate and analyze the sensory indicators of the samples, evaluate the taste of each group of samples, and select the type and amount of flavoring agents. The results are shown in Table 8.

[0107] Table 8 Taste test of flavoring agent dosage

[0108]

[0109] According to the results in Table 8, 0.2% sucralose is preferred as a flavoring agent.

[0110] Experimental Example 4 Study on the effect of the Chinese medicine composition of the present invention on a rat model of cough after infection induced by complex factors

[0111] 84 SD rats were selected, half male and half female. Twelve animals were randomly selected according to body weight as blank control group, and the rest were used as model animals. All model animals were placed in a cigarette exposure box for 30 minutes of smoke exposure every day, and 10 cigarettes were lit each time, once a day, for 10 consecutive days; animals in the blank control group were not operated. All model animals were anesthetized by isoflurane inhalation on the 11th and 13th days, and 0.4 mg / mL LPS solution was dripped alternately on the left and right sides, once on each side, and the nasal drop volume was 1mL / kg; rats in the blank control group were dripped with an equal volume of 0.9% sodium chloride injection. On the 14th day, the model animals were subjected to nebulized inhalation of citric acid solution to induce cough. The rats were placed alone in a 5L sealed beaker, which was sealed with plastic wrap, and a small opening was opened to connect to the nebulizer. 17.5% citric acid solution was placed in the nebulizer for atomization, and the atomized citric acid solution was sprayed into the sealed beaker for 1 minute. The number of rats coughing within 5 minutes from the spray was recorded; rats without coughing were not selected. According to the number of coughs, the model animals were divided into a model control group, a codeine phosphate control group, a Suhuang cough control group, and low-, medium-, and high-dose Shensu cough groups, with 12 rats in each group, half of them male and half female.

[0112] From the 15th day, all animals were gavaged according to 10mL / kg volume, and the blank control group rats were given pure water, and the Suhuang cough control group was given the Suhuang cough capsule content preparation solution (in terms of content, 0.36g / kg, equivalent to the Suhuang clinical rat equivalent dose), and the Shensu cough low, medium and high dose groups were given 2.52g / kg, 5.04g / kg, and 10.08g / kg of Shensu cough granule dry paste powder suspension (prepared by the embodiment of the present invention 1; in terms of crude drug amount, 0.5 times, 1 times, and 2 times of the clinical rat equivalent dose of Shensu cough granules, respectively), once a day, for 7 consecutive days. The codeine phosphate control group was only given codeine phosphate tablets preparation solution (in terms of codeine phosphate content, 5.4mg / kg, equivalent to the clinical rat equivalent dose of codeine phosphate tablets) on the 18th and 21st days, and the rest were given pure water every day.

[0113] One hour after administration on the 18th and 21st days, 17.5% citric acid solution was atomized and inhaled to induce cough in the same manner as above, and the number of coughs of rats within 5 minutes from the start of spraying was recorded. 5 minutes after the coughing frequency test, 75 mg / kg ketamine hydrochloride injection combined with 10 mg / kg xylazine hydrochloride injection was used for intraperitoneal anesthesia, and the abdominal aorta was bled to euthanasia. After the animal was euthanized, the trachea was ligated with a thin thread of equal length before the chest cavity was opened, and then the whole lung was taken out together with the trachea, and the weight was weighed to calculate the lung index. After ligating the right lung, the same section of the trachea and the right lung were fixed with 10% neutral formalin fixative for histopathological examination. 2 ml of 0.9% sodium chloride injection was injected into the left lung with a syringe, and the left lung was lavaged. During the lavage process, the left lung was massaged, and the maximum amount of lavage fluid was aspirated into the EP tube. This was repeated twice, and the alveolar lavage fluid was collected for the determination of white blood cells and their classification.

[0114] The coughing results showed:

[0115] Compared with the blank control group, the coughing frequency of rats in the model control group increased significantly on the 18th and 21st days (P<0.05~0.01);

[0116] Compared with the model control group, the coughing times of rats in the codeine phosphate control group on the 18th and 21st days were significantly reduced (P < 0.05-0.01), the coughing times of rats in the Suhuang cough control group on the 18th and 21st days were significantly reduced (P < 0.05-0.01), the coughing times of rats in the Shensu cough medium-dose group on the 21st day were significantly reduced (P < 0.05), and the coughing times of rats in the Shensu cough high-dose group on the 18th and 21st days were significantly reduced (P < 0.05-0.01). At the same clinical multiple doses, the coughing times of rats in the Shensu cough medium-dose group were not significantly different from those in the Suhuang cough control group (P > 0.05). The results are shown in Table 9.

[0117] Table 9 Statistical results of rat coughing times (±s)

[0118]

[0119] Note: Compared with the blank control group, the model control group *P<0.05, **P<0.01; compared with the model control group, #P<0.05, ## indicates P<0.01.

[0120] Lung weight and lung index results showed:

[0121] Compared with the blank control group, the number of lung organs in the model control group increased significantly (P<0.05);

[0122] Compared with the model control group, the lung weight and organ number of rats in the codeine phosphate control group, the Suhuang cough control group, and the low, medium, and high doses of Shensu cough control groups were not significantly different (P>0.05).

[0123] Table 10 Statistical results of rat lung coefficients (±s)

[0124] Group Number of animals dose Lung weight (g) Lung coefficient Blank control group 12 — 1.435±0.152 0.491±0.063 Model control group 12 — 1.556±0.188 <![CDATA[0.548±0.054 * ]]> Codeine phosphate control group 12 5.4mg / kg 1.477±0.197 0.522±0.055 Suhuang cough control group 12 0.36g / kg 1.495±0.194 0.536±0.047 Low-dose group of Shensu cough suppressant 12 2.52g / kg 1.572±0.156 0.549±0.063 Medium dose group of Shensu cough suppressant 12 5.04g / kg 1.482±0.184 0.536±0.064 High-dose group of Shensu cough suppressant 12 10.08g / kg 1.581±0.184 0.557±0.086

[0125] Note: *P<0.05 compared with the blank control group.

[0126] The results of the white blood cell count in the bronchoalveolar lavage fluid showed:

[0127] Compared with the blank control group, the counts of white blood cells (WBC), neutrophils (NEUT), lymphocytes (LYMPH), and monocytes (MONO) in the bronchoalveolar lavage fluid of rats in the model control group were significantly increased (P<0.05).

[0128] Compared with the model control group, the LYMPH and MONO counts in the bronchoalveolar lavage fluid of rats in the medium-dose Shensu Zhike group were significantly reduced (P<0.05), and the NEUT and MONO counts in the bronchoalveolar lavage fluid of rats in the high-dose Shensu Zhike group were significantly reduced (P<0.05).

[0129] Compared with the model control group, the other parameters of the rats in the codeine phosphate control group, the Suhuang cough control group, and the Shensu cough low, medium, and high dose groups were not statistically different (P>0.05).

[0130] Table 11 Statistical results of white blood cell count in rat bronchoalveolar lavage fluid (±s)

[0131]

[0132] Note: Compared with the negative control group, * indicates P < 0.05, ** indicates P < 0.01; compared with the model group, # indicates P < 0.05, ## indicates P < 0.01.

[0133] Pathological examination results showed:

[0134] Compared with the model control group, the codeine phosphate control group, the Suhuang cough control group, and the Shensu cough low, medium, and high dose groups showed reduced inflammatory cell infiltration in the alveolar cavity / perivascular area, thickening of the alveolar wall, thickening of the bronchial wall, and reduced degree and number of inflammatory cell infiltration in the tracheal mucosal epithelium / submucosa. Except for the negative control group, the proportion of changes in the lungs and trachea of ​​the animals in each group and the comparison between the groups are as follows:

[0135] The comparison of the degree of inflammatory cell infiltration in the alveolar cavity / around blood vessels of the lungs (from severe to mild) is: model control group > commercially available control group > low-dose ginseng and ginger cough suppressant group > medium-dose ginseng and ginger cough suppressant group ≈ high-dose ginseng and ginger cough suppressant group ≈ codeine phosphate control group.

[0136] The comparison of the degree of lung alveolar wall thickening (from severe to mild) is: model control group > Suhuang cough control group > Shensu cough low-dose group > codeine phosphate control group > Shensu cough medium-dose group > Shensu cough high-dose group.

[0137] The comparison of the degree of lung bronchial wall thickening (from severe to mild) is: model control group > Suhuang cough control group > Shensu cough low-dose group ≈ codeine phosphate control group > Shensu cough medium-dose group > Shensu cough high-dose group

[0138] The comparison of the degree of inflammatory cell infiltration in the tracheal mucosal epithelium / submucosa (from severe to mild) is: model control group > Suhuang cough control group ≈ Shensu cough high-dose group ≈ codeine phosphate control group > Shensu cough low-dose group > Shensu cough medium-dose group.

[0139] Table 12 Statistical table of histological examination results of experimental animals (n=12)

[0140]

[0141]

[0142] Note: The degree of histological changes is represented by -, ±, +, ++, and +++ to indicate normal, slight, mild, moderate, and severe.

[0143] The experimental results showed that Shensu Cough-relieving Granules had a good therapeutic effect on the rat post-infection cough model induced by smoke combined with lipopolysaccharide nasal drops and citric acid aerosol when administered continuously for 7 days at a dose of 5.04g / kg and 10.08g / kg (approximately 1 times and 2 times the clinical dose). The main manifestation was that Shensu Cough-relieving Granules had a significant effect on reducing the number of coughs in model rats at a dose of 5.04g / kg and 10.08g / kg. Shensu Cough-relieving Granules could improve the inflammatory cell infiltration in the alveolar cavity / around blood vessels, alveolar wall thickening, bronchial wall thickening and tracheal mucosal epithelium / submucosa of the lungs of model animals.

[0144] At equal clinical multiple doses, the antitussive effect of Shensu Cough Granules administered for 7 days on the rat post-infectious cough model induced by smoke combined with lipopolysaccharide nasal drops and citric acid aerosolization was comparable to that of Suhuang Cough Granules, but it was slightly better than Suhuang Cough Granules in improving the degree of inflammatory cell infiltration in the alveolar cavity / around blood vessels, alveolar wall thickening, bronchial wall thickening, and inflammatory cell infiltration in the tracheal mucosal epithelium / submucosa.

[0145] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. It should be pointed out that a person skilled in the art can make several improvements and modifications without departing from the technical principles of the present invention, and these improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A Chinese medicine composition for invigorating qi, soothing wind, moistening the lungs and relieving cough, characterized in that: The Chinese medicine composition is composed of the following raw materials in parts by weight: 9-15 parts of Pseudostellariae Radix, 5-9 parts of Perilla Folium, 4-8 parts of Platycodon Grandiflorum, 5-8 parts of stir-fried Apricot Kernel, 6-10 parts of Uncaria Rhynchophylla, 6-10 parts of stir-fried Atractylodes Macrocephala, 6-10 parts of Aster tataricus, and 2-6 parts of roasted Licorice Root.

2. The Chinese medicine composition for invigorating qi, dispersing wind, moistening lungs and relieving cough as claimed in claim 1, characterized in that: The Chinese medicine composition is composed of the following raw materials in parts by weight: 9-11 parts of Pseudostellariae Radix, 6-8 parts of Perilla Folium, 5-7 parts of Platycodon Grandiflorum, 5-7 parts of stir-fried Apricot Kernel, 7-9 parts of Uncaria Rhynchophylla, 7-9 parts of stir-fried Atractylodes Macrocephala, 7-9 parts of Aster tataricus, and 3-5 parts of roasted Licorice Root.

3. The Chinese medicine composition for invigorating qi, dispersing wind, moistening lungs and relieving cough as claimed in claim 1, characterized in that: The Chinese medicine composition is composed of the following raw materials in parts by weight: 12 parts of Pseudostellariae Radix, 7 parts of Perilla Folium, 7 parts of Platycodon Grandiflorum, 7 parts of stir-fried Apricot Kernel, 10 parts of Uncaria Rhynchophylla, 10 parts of stir-fried Atractylodes Macrocephala, 10 parts of Aster tataricus, and 5 parts of roasted Licorice Root.

4. The Chinese medicine composition for invigorating qi, dispersing wind, moistening lungs and relieving cough as claimed in claim 1, characterized in that: The Chinese medicine composition is composed of the following raw materials in parts by weight: 10 parts of Pseudostellariae Radix, 6 parts of Perilla Folium, 6 parts of Platycodon Grandiflorum, 6 parts of stir-fried Apricot Kernel, 8 parts of Uncaria Rhynchophylla, 8 parts of stir-fried Atractylodes Macrocephala, 8 parts of Aster tataricus, and 4 parts of roasted Licorice Root.

5. A method for preparing the Chinese medicine composition for invigorating qi, dispersing wind, moistening lungs and relieving cough as claimed in any one of claims 1 to 4, characterized in that: The following steps are included in sequence: Step S1, weighing raw medicinal materials according to the weight ratio; Step S2, boiling the raw medicinal materials with water for 1 to 3 times, and filtering the decoction; Step S3, concentrating the extract to an extract concentrate having a relative density of 1.20 to 1.30 at 50° C. to 90° C.; Step S4, drying the extracted concentrated liquid.

6. The method for preparing the Chinese medicine composition for invigorating qi, soothing wind, moistening lungs and relieving cough according to claim 5, characterized in that: In step S2, take the medicinal materials except Uncaria rhynchophylla, add 8 times the amount of water, boil twice, each time for 1 hour, and filter the decoction; add Uncaria rhynchophylla to the medicinal residue, add 8 times the amount of water, boil once, each time for 0.5 hour.

7. The method for preparing the Chinese medicine composition for invigorating qi, dispelling wind, moistening lungs and relieving cough as claimed in claim 5, characterized in that: In step S4, when the drying method is reduced pressure drying, the temperature of reduced pressure drying is 50° C. to 80° C., and the negative pressure is 0.06 to -0.1 MPa; or, In step S4, when the drying method is spray drying, 15% dextrin is added to the extraction concentrate for spray drying.

8. A preparation of a traditional Chinese medicine composition for invigorating qi, soothing wind, moistening the lungs and relieving cough as claimed in any one of claims 1 to 4, characterized in that: The preparation is a granule, tablet, capsule, oral liquid preparation or pill.

9. A method for preparing the Chinese medicine composition for invigorating qi, soothing wind, moistening lungs and relieving cough as claimed in claim 8, characterized in that: The following steps are included in sequence: Step S1, weighing raw medicinal materials according to the weight ratio; Step S2, boiling the raw medicinal materials with water for 1 to 3 times, and filtering the decoction; Step S3, concentrating the extract to an extract concentrate having a relative density of 1.20 to 1.30 at 50° C. to 90° C.; Step S4, drying the extracted concentrated liquid to obtain a dry paste; Step S5: After the dry paste is crushed, auxiliary materials are added and granulated to prepare a preparation.

10. The method for preparing the Chinese medicine composition for invigorating qi, soothing wind, moistening lungs and relieving cough as claimed in claim 9, characterized in that: In the step S2, take the medicinal materials except Uncaria rhynchophylla, add 8 times the amount of water, decoct twice, each time for 1 hour, and filter the decoction; add Uncaria rhynchophylla to the medicinal residue, add 8 times the amount of water, decoct once, each time for 0.5 hour; In step S4, when the drying method is reduced pressure drying, the temperature of reduced pressure drying is 50° C. to 80° C., and the negative pressure is 0.06 to -0.1 MPa; or, In step S4, when the drying method is spray drying, 15% dextrin is added to the extraction concentrate for spray drying.

11. A method for preparing the Chinese medicine composition for invigorating qi, soothing wind, moistening lungs and relieving cough as claimed in claim 9, characterized in that: In step S5, the granulation method is dry granulation, the auxiliary material is a combination of one or more of soluble starch, dextrin, and microcrystalline cellulose; the sweetener is a combination of one or more of sucralose, steviol glycoside, and aspartame; or, In step S5, the granulation method is to add filler and 0.2% sucralose according to the ratio of dry paste powder to filler of 1:0.75 for wet granulation; wherein the ratio of the filler is dextrin: soluble starch = 1:

4.

12. Use of the traditional Chinese medicine composition for invigorating qi, soothing wind, moistening the lungs and relieving cough as claimed in any one of claims 1 to 4 in treating and / or preventing post-infectious cough.

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