Composition with cough relieving effect as well as preparation method and application thereof

Abstract

The invention discloses a composition with a cough relieving effect as well as a preparation method and application thereof, and relates to the technical field of traditional Chinese medicines. The method comprises the following steps: crushing fritillaria, adding ethanol for infiltration, and performing percolation extraction to obtain fritillaria percolation liquid; adding water into gypsum, decocting and extracting to obtain gypsum decoction; the preparation method comprises the following steps: crushing semen armeniacae amarae, pinellia ternate and ginkgo kernels, putting into a frying bag, mixing with ephedra, lumbricus, white mulberry root-bark, thesium chinense, liquorice, fructus perillae and semen lepidii, adding ethanol, heating, refluxing and extracting to obtain a mixed extracting solution 1; decocting and extracting radix scutellariae to obtain radix scutellariae decoction, and preparing radix scutellariae extract fine powder; adding water into honeysuckle and tussilago farfara, decocting and extracting to obtain a mixed extracting solution 2; mixing and concentrating the products to obtain clear paste; and uniformly mixing the clear paste with the scutellaria baicalensis extract fine powder to obtain the composition with the cough relieving effect. By improving an extraction method and a concentration method of the traditional Chinese medicine composition, the transfer rate of effective components in the obtained extract is higher, and the traditional Chinese medicine composition has a better effect on treating cough.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and in particular to a composition with antitussive effect and a preparation method and application thereof. Background Art

[0002] Coughing is an important protective reflex that can prevent aspiration and clear irritants and excess secretions in the airways. Involuntary coughing is a reflex activated by sensory nerves in the afferent area of ​​the vagus nerve. After airway sensory nociceptors detect potential harmful stimuli, they transmit nerve impulses to the nucleus tractus solitarius and the trigeminal nerve in the brainstem, and then to higher control centers through secondary neurons to regulate the cough reflex.

[0003] Cough is common in clinical practice. The causes include colds, bronchitis, emphysema, asthma, etc. It is an airway inflammation involving multiple cells and cell components. It is also an immune-mediated systemic inflammatory disease. The imbalance of cytokine and inflammatory factor release network plays an important role in the development of acute cough. After the acute symptoms such as fever, nasal congestion, runny nose, sore throat and cough disappear, the main manifestation is a stubborn, irritating dry cough. On the one hand, severe cough can affect the patient's normal life and sleep, resulting in a decrease in their quality of life; on the other hand, due to changes in the microenvironment in the airway, the congested and edematous mucosa is more sensitive to external stimuli. Therefore, when affected by external factors, secondary bacterial infection may occur, aggravating the condition.

[0004] Chinese patent CN102580037A discloses a Chinese medicine composition for treating cough after wind-cold infection, which is composed of effective ingredients and medically acceptable excipients, characterized in that the effective ingredients are made of raw materials such as 4-8 parts by weight of roasted ephedra, 9-11 parts by weight of coltsfoot flower, 2-3 parts by weight of asarum, 9-11 parts by weight of peucedanum, 8-10 parts by weight of northern apricot, 14-16 parts by weight of follicle, 9-11 parts by weight of pinellia tuber, 9-11 parts by weight of schizonepeta spicate, 9-11 parts by weight of ginger, 4-6 parts by weight of schisandra chinensis and 4-6 parts by weight of raw liquorice. The Chinese medicine composition described in the invention has the effects of dispelling wind and cold, promoting lung function, resolving phlegm and relieving cough, and can improve the symptoms of patients with cough after wind-cold infection.

[0005] Chinese patent CN108653550A discloses an Ephedra scutellariae cough relieving medicine and its preparation method and detection method. The Ephedra scutellariae cough relieving medicine is made of the following medicinal raw materials in parts by weight: 110-125g honey ephedra, 110-125g mulberry bark, 225-240g honeysuckle, 110-125g scutellariae, 205-220g gypsum, 110-125g thunbergii, 110-125g bitter almond, 110-125g perilla seed, 110-125g coltsfoot flower, 110-125g scutellariae, 205-220g earthworm, 75-90g ginger pinellia, 110-125g stir-fried ginkgo nuts, and 75-90g roasted licorice. The invention provides a method for simultaneously determining the content of active ingredients in Maqin cough medicine by high performance liquid chromatography, and also provides a new use of Maqin cough medicine in the preparation of treatment of chronic obstructive pulmonary disease. The extract obtained by the extraction method of the patent still cannot ensure full utilization of active ingredients.

[0006] Chinese patent CN106620498A discloses a traditional Chinese medicine composition for treating cough after a cold, which is composed of the following raw materials in parts by weight: 620 grams of Clematis chinensis, 620 grams of Curcuma aromatica, 310 grams of Acorus calamus, and 36 grams of mint. Preparation method: add 6-12 times water to the total amount of the medicinal materials of Clematis, mint, Acorus calamus and Curcuma, extract volatile oil by steam distillation for 5-9 hours, collect volatile oil, add Tween 80 for solubilization or ethanol for dissolution, and set aside; filter the steam distillation extract to obtain the mother liquor and filter residue; add 6-10 times water to the filter residue and decoct it 1-3 times, each time for 1-3 hours, combine the decoction and the mother liquor, concentrate the supernatant, add 75-95% ethanol to make the alcohol content reach 65-85%, refrigerate and stand, take out, filter, and decompress the filtrate to recover ethanol until there is no alcohol taste; add the solubilized volatile oil and conventional medicinal excipients, and adopt the conventional preparation method in Chinese medicine pharmacy to prepare a suitable dosage form. The invention also provides the use of the Chinese medicine composition in the preparation of drugs for treating infectious cough and various chronic coughs.

[0007] At present, there are many traditional Chinese medicine formulas for treating cough, but there is still a lack of technical solutions based on the extraction of effective ingredients and making breakthroughs in technology. Summary of the invention

[0008] In view of this, the purpose of the present invention is to provide a composition with antitussive effect and its preparation method and application. By improving the extraction method and concentration method of the traditional Chinese medicine formula, the obtained extract has a higher transfer rate and has a better effect on the treatment of cough.

[0009] To achieve the above-mentioned object of the invention, the technical solution of the present invention is as follows:

[0010] In one aspect, the present invention provides a method for preparing a composition having a cough relieving effect, comprising the following steps:

[0011] (1) crushing Fritillaria to obtain Fritillaria fine powder, soaking it in ethanol, and extracting it by percolation to obtain Fritillaria percolate;

[0012] (2) gypsum is boiled in water for 1-3 times, the decoctions are combined and filtered to obtain gypsum decoction;

[0013] (3) Grind bitter almonds, pinellia tuber, and ginkgo kernel, put them in a decoction bag, and combine them with ephedra, earthworm, mulberry bark, lily, licorice, perilla seed, and scutellaria baicalensis seed, add ethanol, heat and reflux for extraction 2-4 times, and combine the extracts to obtain a mixed extract 1;

[0014] (4) decoct the Scutellaria baicalensis for 2-5 times, filter the decoction, combine the filtrate, and obtain the Scutellaria baicalensis decoction; concentrate the Scutellaria baicalensis decoction, adjust the pH value to 1.5-2.5, let it stand for 1-5 hours, centrifuge to obtain a crude extract, wash the crude extract until the pH value reaches 3.5-4.5, dry, and crush to obtain a fine powder of the Scutellaria baicalensis extract;

[0015] (5) decoct honeysuckle and coltsfoot flower in water for 1-3 times, combine the decoctions, filter, and obtain mixed extract 2;

[0016] (6) Mix the Fritillaria percolate, gypsum decoction, mixed extract 1, and mixed extract 2, and concentrate to obtain a clear paste;

[0017] (7) The paste obtained in step (6) is mixed with the fine powder of the scutellaria baicalensis extract obtained in step (4) to obtain the composition having the effect of relieving cough.

[0018] Preferably, in the preparation method, the raw material formula is: 110-125 weight parts of honey ephedra, 110-125 weight parts of mulberry bark, 225-240 weight parts of honeysuckle, 110-125 weight parts of scutellaria, 205-220 weight parts of celery, 205-220 weight parts of gypsum, 110-125 weight parts of thunbergii, 110-125 weight parts of bitter almonds, 110-125 weight parts of perilla seeds, 110-125 weight parts of coltsfoot flowers, 110-125 weight parts of scutellaria seeds, 205-220 weight parts of earthworms, 75-90 weight parts of ginger pinellia, 110-125 weight parts of stir-fried ginkgo nuts, and 75-90 weight parts of roasted licorice.

[0019] Further preferred is: 117 parts by weight of honey ephedra, 117 parts by weight of mulberry bark, 233 parts by weight of honeysuckle, 117 parts by weight of scutellaria, 212 parts by weight of clematis, 212 parts by weight of gypsum, 117 parts by weight of thunbergia, 117 parts by weight of bitter almond, 117 parts by weight of perilla seed, 117 parts by weight of coltsfoot flower, 117 parts by weight of scutellaria seed, 212 parts by weight of earthworm, 83 parts by weight of pinellia tuber, 117 parts by weight of stir-fried ginkgo kernels, and 83 parts by weight of roasted licorice.

[0020] Preferably, in step (1), the ethanol refers to an ethanol aqueous solution, wherein the volume concentration of ethanol is 60-80%, more preferably 70%.

[0021] Preferably, in step (1), the mass of the ethanol is 5-15 times the mass of the Fritillaria, more preferably 8-10 times, and even more preferably 9 times.

[0022] Preferably, in step (1), the infiltration time is 6-12 h, more preferably 8-10 h, and even more preferably 9 h.

[0023] Preferably, in step (1), the diafiltration extraction rate is 1-5 mL / kg / min, more preferably 3 mL / kg / min.

[0024] Preferably, in step (2), the decoction extraction is performed twice, 4-6 times the weight of water is added each time, and the decoction extraction time is 0.5-1h each time; further preferably, 5 times the weight of water is added each time, and the decoction extraction time is 50min each time.

[0025] Preferably, in step (3), the pulverization is performed to a size of less than 80 meshes.

[0026] Preferably, in step (3), the ethanol refers to an ethanol aqueous solution, wherein the volume concentration of ethanol is 35-45%, and more preferably 40%.

[0027] Preferably, in step (3), the heating reflux extraction is performed 3 times, and more preferably: 6-10 times the amount of ethanol is added in the first time, 4-8 times the amount of ethanol is added in the second and third times, and each extraction is performed for 0.5-1.5 hours. Most preferably: 8 times the amount of ethanol is added in the first time, 6 times the amount of ethanol is added in the second and third times, and each extraction is performed for 1 hour.

[0028] Preferably, in step (4), the concentration is to concentrate to a relative density of 1.10-1.20.

[0029] Preferably, in step (4), the drying is performed until the moisture content is no higher than 5.0%.

[0030] Preferably, step (4) is specifically as follows: decocting and extracting Scutellaria baicalensis for 3 times, adding 8 times the amount of ethanol for the first time, and adding 6 times the amount of ethanol for the second and third times, each extraction for 1 hour, filtering the decoction, combining the filtrate, and obtaining the Scutellaria baicalensis decoction; concentrating the Scutellaria baicalensis decoction, adjusting the pH value to 2.0, standing for 3 hours, centrifuging to obtain a crude extract, washing the crude extract until the pH value reaches 4.0, drying, and crushing to obtain a fine powder of Scutellaria baicalensis extract.

[0031] Preferably, in step (5), the decoction is performed twice; more preferably, the first time 15-20 times the amount of water is added, and the decoction is performed for 15-25 minutes; the second time 8-12 times the amount of water is added, and the decoction is performed for 10-20 minutes. Most preferably, the first time 15 times the amount of water is added, and the decoction is performed for 20 minutes; the second time 10 times the amount of water is added, and the decoction is performed for 15 minutes.

[0032] Preferably, in step (6), the concentration is double-effect concentration.

[0033] Further preferably, the conditions for the double-effect concentration are: steam pressure: 0.1 to 0.2 MPa; first-effect vacuum degree: -0.05 to -0.1 MPa, first-effect concentration temperature: 60 to 80°C; second-effect vacuum degree: -0.05 to -0.1 MPa, second-effect concentration temperature: 50 to 70°C.

[0034] Preferably, in step (6), the concentration is to a relative density of 1.15-1.25 (50-60° C.).

[0035] In a second aspect, the present invention provides a composition having a cough relieving effect prepared by the above preparation method.

[0036] In a third aspect, the present invention provides use of the above-mentioned composition with antitussive efficacy in the preparation of a drug for treating antitussive.

[0037] Preferably, the cough relieving agent is lung clearing and phlegm dissolving, cough relieving and asthma relieving. It is used for acute bronchitis and acute attack of chronic bronchitis, which is caused by phlegm-heat stagnation in the lungs, with symptoms such as cough, wheezing, yellow or thick phlegm, fever, dry mouth, yellow and greasy tongue coating, and red tongue.

[0038] In a fourth aspect, the present invention provides a medicine, the effective ingredient of which includes the above-mentioned Chinese medicine composition.

[0039] The drug can be prepared into dosage forms such as granules, pills, capsules, mixtures, powders, tablets, syrups, etc., and suitable drug carriers in the art can be selected for different dosage forms.

[0040] The pharmaceutical carrier used can be solid, liquid or gas. Examples of solid carriers include dextrin, maltodextrin, sucrose, lactose, starch, kaolin, talc, gelatin, agar, pectin, gum arabic, magnesium stearate and stearic acid. Examples of liquid carriers include syrup, peanut oil, olive oil and water. Examples of gaseous carriers include carbon dioxide and nitrogen.

[0041] When preparing the composition for oral dosage form, any convenient pharmaceutical medium can be used. For example, water, ethanol, oil, alcohol, flavoring agent, preservative, coloring agent, etc. can be used to form oral liquid preparations, such as suspensions and solutions; while carriers, such as dextrin, maltodextrin, starch, sugar, microcrystalline cellulose, diluent, granulating agent, emulsifier, lubricant, binder, disintegrant can be used to form oral solid preparations, such as granules, powders, capsules and tablets. Granules, tablets and capsules are preferred oral dosage units using solid pharmaceutical carriers due to their ease of administration. Tablets can be coated using standard aqueous or non-aqueous techniques.

[0042] Tablets containing the Chinese medicine composition of the present invention can be prepared by tableting or molding, and one or more auxiliary ingredients or adjuvants can be used. The active ingredient can be tableted in a free-flowing form (such as powder or granules) in a suitable machine, and can be mixed with a binder, a lubricant, an inert diluent, a surfactant or a dispersant to prepare a tablet. Molded tablets can be molded in a suitable machine, that is, a powdered mixture moistened with an inert liquid diluent, each tablet preferably contains about 0.05 mg to about 5 g of active ingredient, and each sachet or capsule preferably contains about 0.05 mg to about 5 g of active ingredient. For example, a preparation intended for oral administration to humans may contain about 0.5 mg to about 5 g of active drug, mixed with an appropriate and convenient carrier material, which may account for about 5% to 95% of the total composition. The unit dosage form usually contains about 1 mg to about 2 g of active ingredient, usually 25 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 800 mg or 1000 mg.

[0043] The pharmaceutical composition suitable for parenteral administration in the present invention can be prepared as an aqueous solution or suspension of the active compound, and can include a suitable surfactant, such as hydroxypropylcellulose. Dispersions can also be prepared in glycerol, liquid polyethylene glycol and its oil mixture. In addition, preservatives can be added to prevent the harmful growth of microorganisms.

[0044] Medicine of the present invention can be in the form suitable for topical use, for example aerosol, cream, ointment, lotion, powder or the like. In addition, composition can be in the form suitable for transdermal administration device. Can use Chinese medicine composition of the present invention, prepare these prescriptions by conventional processing method. For example, by mixing hydrophilic material and water, and about 5wt% to about 10wt% of compound, prepare cream or ointment with required consistency.

[0045] The medicine of the present invention can be in a form suitable for rectal administration, wherein the carrier is a solid. Preferably, the mixture is made into a unit dose suppository. Suitable carriers include cocoa butter and other materials commonly used in the art. Suppositories can be prepared by first forming a composition containing a softened or melted carrier, followed by cooling and shaping in a mold.

[0046] In addition to the above-mentioned carrier components, the above-mentioned pharmaceutical preparations may include (if applicable) one or more additional carrier components, such as diluents, buffers, flavoring agents, adhesives, surfactants, thickeners, lubricants, preservatives (including antioxidants), etc. In addition, other excipients, such as lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, colorants and flavoring agents, etc., may be added, and the components containing the Chinese medicine composition of the present invention may also be prepared in the form of powder or concentrated solution.

[0047] The beneficial effects of the present invention are:

[0048] (1) The present invention further obtains an extract with significant antitussive effect by optimizing the extraction method.

[0049] (2) The present invention can achieve efficient extraction of effective ingredients and improve the pharmacological activity of the extract by disassembling the formula composition and extracting different medicinal flavors separately and specifically.

[0050] (3) The present invention has found that combining different extracts and then concentrating them greatly improves the transfer rate of active ingredients, reduces the loss of active ingredients, and thus improves the efficacy, compared with the single concentration treatment. DETAILED DESCRIPTION

[0051] In order to make the technical means, creative features, purpose and efficacy of the present invention easy to understand, the present invention is further explained in conjunction with specific embodiments below, but the following embodiments are only preferred embodiments of the present invention, not all. Based on the embodiments in the implementation mode, other embodiments obtained by those skilled in the art without creative work all belong to the protection scope of the present invention. In the following embodiments, unless otherwise specified, the operating methods used are conventional operating methods, the equipment used are conventional equipment, and the equipment and materials used in each embodiment are the same. Unless otherwise specified, the percentages involved are all mass percentages. In the following embodiments, unless otherwise specified, the concentration methods are all evaporation concentrations.

[0052] In the following embodiments, the medicinal material formula is suitable within the following ranges, and the extraction method of the present invention can achieve improved drug efficacy: 110-125 parts by weight of honey ephedra, 110-125 parts by weight of mulberry bark, 225-240 parts by weight of honeysuckle, 110-125 parts by weight of scutellaria, 205-220 parts by weight of celery, 205-220 parts by weight of gypsum, 110-125 parts by weight of thunbergii, 110-125 parts by weight of bitter almonds, 110-125 parts by weight of perilla seeds, 110-125 parts by weight of coltsfoot flowers, 110-125 parts by weight of scutellaria, 205-220 parts by weight of earthworms, 75-90 parts by weight of ginger pinellia, 110-125 parts by weight of stir-fried ginkgo nuts, and 75-90 parts by weight of roasted licorice.

[0053] In a specific embodiment, the exemplary formula selected is: 117 parts by weight of honey ephedra, 117 parts by weight of mulberry bark, 233 parts by weight of honeysuckle, 117 parts by weight of scutellaria, 212 parts by weight of clematis, 212 parts by weight of gypsum, 117 parts by weight of thunbergia, 117 parts by weight of bitter almond, 117 parts by weight of perilla seed, 117 parts by weight of coltsfoot flower, 117 parts by weight of scutellaria seed, 212 parts by weight of earthworm, 83 parts by weight of pinellia tuber, 117 parts by weight of stir-fried ginkgo kernels, and 83 parts by weight of roasted licorice.

[0054] Example 1

[0055] A method for preparing a composition having a cough relieving effect comprises the following steps:

[0056] (1) Crush the Fritillaria thunbergii to less than 100 meshes to obtain fine powder, add 9 times the weight of 70% ethanol to soak for 9 hours, and perform percolation extraction at a percolation extraction rate of 3 mL / kg / min to obtain Fritillaria thunbergii percolate;

[0057] (2) Gypsum is decocted and extracted twice with water added 5 times its weight each time. The decoctions are combined and filtered to obtain gypsum decoction;

[0058] (3) Grind bitter almonds, ginger pinellia, and fried ginkgo nuts to less than 80 mesh, put them in a frying bag, and combine them with honey ephedra, earthworm, mulberry bark, celery, roasted liquorice, perilla seed, and scutellaria baicalensis seed. Add 40% ethanol and heat under reflux for extraction three times. Add 8 times the amount of ethanol for the first extraction, and add 6 times the amount of ethanol for the second and third extractions. Each extraction lasts for 1 hour. Combine the extracts and filter to obtain a mixed extract 1.

[0059] (4) decocting and extracting Scutellaria baicalensis for 3 times, adding 8 times the amount of ethanol for the first time, and adding 6 times the amount of ethanol for the second and third times, each extraction for 1 hour, filtering the decoction, combining the filtrate, and obtaining the Scutellaria baicalensis decoction; concentrating the Scutellaria baicalensis decoction to a relative density of 1.10-1.20, adjusting the pH value to 2.0, standing for 3 hours, and centrifuging to obtain a crude extract, washing the crude extract to a pH value of 4.0, drying to a moisture content of no more than 5.0%, and crushing to obtain a fine powder of Scutellaria baicalensis extract;

[0060] (5) Decoction the honeysuckle and coltsfoot flowers with water for 2 times, add 15 times the amount of water for the first time and decoct for 20 min; add 10 times the amount of water for the second time and decoct for 15 min, combine the decoctions, filter, and obtain mixed extract 2;

[0061] (6) mixing the Fritillaria percolate, gypsum decoction, mixed extract 1, and mixed extract 2, and performing double-effect concentration to obtain a clear paste;

[0062] The conditions for double-effect concentration are: steam pressure: 0.1MPa; first-effect vacuum degree: -0.05~-0.1MPa, first-effect concentration temperature: 70°C; second-effect vacuum degree: -0.05~-0.1MPa, second-effect concentration temperature: 60°C. The relative density of the final clear paste is 1.20 (50-60°C).

[0063] (7) The paste obtained in step (6) is mixed with the fine powder of the scutellaria baicalensis extract obtained in step (4) to obtain the composition having the effect of relieving cough.

[0064] Example 2

[0065] A method for preparing a composition having a cough relieving effect comprises the following steps:

[0066] (1) crushing Fritillaria thunbergii to less than 100 mesh to obtain fine powder, adding 15 times the weight of 60% ethanol to soak for 6 hours, and percolating at a percolation rate of 5 mL / kg / min to obtain Fritillaria thunbergii percolate;

[0067] (2) Gypsum was decocted and extracted twice with 6 times the weight of water added each time. The decoctions were combined and filtered to obtain gypsum decoction.

[0068] (3) Grind bitter almonds, ginger pinellia, and fried ginkgo nuts to less than 80 mesh, put them in a frying bag, and combine them with honey ephedra, earthworm, mulberry bark, celery, roasted liquorice, perilla seed, and scutellaria baicalensis seed. Add 35% ethanol and heat under reflux for extraction three times. Add 10 times the amount of ethanol for the first extraction, and 8 times the amount of ethanol for the second and third extractions. Each extraction takes 1.5 hours. Combine the extracts and filter to obtain a mixed extract 1.

[0069] (4) decocting and extracting Scutellaria baicalensis for 3 times, adding 8 times the amount of ethanol for the first time, and adding 6 times the amount of ethanol for the second and third times, each extraction for 1 hour, filtering the decoction, combining the filtrate, and obtaining the Scutellaria baicalensis decoction; concentrating the Scutellaria baicalensis decoction to a relative density of 1.10-1.20, adjusting the pH value to 2.0, standing for 3 hours, and centrifuging to obtain a crude extract, washing the crude extract to a pH value of 4.0, drying to a moisture content of no more than 5.0%, and crushing to obtain a fine powder of Scutellaria baicalensis extract;

[0070] (5) Decoction the honeysuckle and coltsfoot flowers with water for 2 times, add 15 times the amount of water for the first time and decoct for 15 min; add 12 times the amount of water for the second time and decoct for 20 min, combine the decoctions, filter, and obtain mixed extract 2;

[0071] (6) mixing the Fritillaria percolate, gypsum decoction, mixed extract 1, and mixed extract 2, and performing double-effect concentration to obtain a clear paste;

[0072] The conditions for double-effect concentration are: steam pressure: 0.1MPa; vacuum degree of the first effect: -0.05~-0.1MPa, concentration temperature of the first effect: 70°C; vacuum degree of the second effect: -0.05~-0.1MPa, concentration temperature of the second effect: 60°C. The relative density of the final clear paste is 1.25 (50-60°C).

[0073] (7) The paste obtained in step (6) is mixed with the fine powder of the scutellaria baicalensis extract obtained in step (4) to obtain the composition having the effect of relieving cough.

[0074] Example 3

[0075] A method for preparing a composition having a cough relieving effect comprises the following steps:

[0076] (1) Crush Fritillaria thunbergii to less than 100 meshes to obtain fine powder, add 15 times the weight of 80% ethanol to soak for 12 hours, and perform percolation extraction at a percolation extraction rate of 1 mL / kg / min to obtain Fritillaria thunbergii percolate;

[0077] (2) Gypsum is decocted and extracted twice with water added 4 times its weight each time. The decoctions are combined and filtered to obtain gypsum decoction;

[0078] (3) Grind bitter almonds, ginger pinellia, and fried ginkgo nuts to less than 80 mesh, put them in a frying bag, and combine them with honey ephedra, earthworm, mulberry bark, celery, roasted liquorice, perilla seed, and scutellaria baicalensis seed. Add 45% ethanol and heat under reflux for extraction three times. Add 6 times the amount of ethanol for the first extraction, and 4 times the amount of ethanol for the second and third extractions. Each extraction lasts for 0.5 hour. Combine the extracts and filter to obtain a mixed extract 1.

[0079] (4) decocting and extracting Scutellaria baicalensis for 3 times, adding 8 times the amount of ethanol for the first time, and adding 6 times the amount of ethanol for the second and third times, each extraction for 1 hour, filtering the decoction, combining the filtrate, and obtaining the Scutellaria baicalensis decoction; concentrating the Scutellaria baicalensis decoction to a relative density of 1.10-1.20, adjusting the pH value to 2.0, standing for 3 hours, and centrifuging to obtain a crude extract, washing the crude extract to a pH value of 4.0, drying to a moisture content of no more than 5.0%, and crushing to obtain a fine powder of Scutellaria baicalensis extract;

[0080] (5) Decoction the honeysuckle and coltsfoot flowers with water for 2 times, add 20 times the amount of water for the first time and decoct for 25 minutes; add 8 times the amount of water for the second time and decoct for 10 minutes, combine the decoctions, filter, and obtain mixed extract 2;

[0081] (6) mixing the Fritillaria percolate, gypsum decoction, mixed extract 1, and mixed extract 2, and performing double-effect concentration to obtain a clear paste;

[0082] The conditions for double-effect concentration are: steam pressure: 0.1MPa; first-effect vacuum degree: -0.05~-0.1MPa, first-effect concentration temperature: 70°C; second-effect vacuum degree: -0.05~-0.1MPa, second-effect concentration temperature: 60°C. The relative density of the final clear paste is 1.20 (50-60°C).

[0083] (7) The paste obtained in step (6) is mixed with the fine powder of the scutellaria baicalensis extract obtained in step (4) to obtain the composition having the effect of relieving cough.

[0084] Comparative Example 1

[0085] The preparation was carried out according to the steps described in paragraphs 0024-0028 of the specification of Chinese patent CN108653550A.

[0086] Comparative Example 2

[0087] The difference from Example 1 is that in step (1), Fritillaria thunbergii is crushed to obtain Fritillaria thunbergii fine powder, which is then decocted and extracted with 5 times the weight of water to obtain Fritillaria thunbergii decoction, which is used to replace Fritillaria thunbergii percolation liquid. The other conditions are the same.

[0088] Comparative Example 3

[0089] A method for preparing a composition having a cough relieving effect comprises the following steps:

[0090] (1) Crush the Fritillaria thunbergii to less than 100 meshes to obtain fine powder, soak it in 9 times the weight of 70% ethanol for 9 hours, and extract it by percolation at a rate of 3 mL / kg / min to obtain Fritillaria thunbergii percolation liquid, and concentrate it to a clear paste of 1 with a relative density of 1.3 (80-85° C.);

[0091] (2) Gypsum was decocted and extracted twice with 5 times the weight of water added each time. The decocting and extraction time was 50 min each time. The decoctions were combined, filtered, and concentrated to a clear paste 2 with a relative density of 1.3 (80-85°C);

[0092] (3) Bitter almonds, ginger pinellia, and fried ginkgo nuts are crushed to less than 80 mesh, placed in a decoction bag, and combined with honey ephedra, earthworm, mulberry bark, celery, roasted liquorice, perilla seed, and scutellaria baicalensis seed. 40% ethanol is added and heated under reflux for extraction three times. Eight times the amount of ethanol is added for the first extraction, and six times the amount of ethanol is added for the second and third extractions. Each extraction lasts for 1 hour. The extracts are combined and filtered to obtain a mixed extract 1, which is concentrated to a clear paste 3 with a relative density of 1.3 (80-85°C);

[0093] (4) decocting and extracting Scutellaria baicalensis for 3 times, adding 8 times the amount of ethanol for the first time, and adding 6 times the amount of ethanol for the second and third times, each extraction for 1 hour, filtering the decoction, combining the filtrate, and obtaining the Scutellaria baicalensis decoction; concentrating the Scutellaria baicalensis decoction to a relative density of 1.10-1.20, adjusting the pH value to 2.0, standing for 3 hours, and centrifuging to obtain a crude extract, washing the crude extract to a pH value of 4.0, drying to a moisture content of no more than 5.0%, and crushing to obtain a fine powder of Scutellaria baicalensis extract;

[0094] (5) decocting honeysuckle and coltsfoot flower with water for extraction twice, adding 15 times the amount of water for the first time and decocting for 20 minutes; adding 10 times the amount of water for the second time and decocting for 15 minutes, combining the decoctions, filtering, obtaining a mixed extract 2, and concentrating to a clear paste 4 with a relative density of 1.00 to 1.10 (50 to 60° C.);

[0095] (6) Mix the clear paste 1, the clear paste 2, the clear paste 3, the clear paste 4 and the fine powder of the scutellaria baicalensis extract to obtain the composition with the cough relieving effect.

[0096] Comparative Example 4

[0097] A method for preparing a composition having a cough relieving effect comprises the following steps:

[0098] (1) Crush the Fritillaria thunbergii to less than 100 meshes to obtain fine powder, add 9 times the weight of 70% ethanol to soak for 9 hours, and perform percolation extraction at a percolation extraction rate of 3 mL / kg / min to obtain Fritillaria thunbergii percolate;

[0099] (2) Gypsum is decocted and extracted twice with water added 5 times its weight each time. The decoctions are combined and filtered to obtain gypsum decoction;

[0100] (3) Grind bitter almonds, ginger pinellia, and fried ginkgo nuts to less than 80 mesh, put them in a frying bag, and combine them with honey ephedra, honeysuckle, coltsfoot flower, roasted liquorice, perilla seed, and scutellaria baicalensis seed. Add 40% ethanol and heat under reflux for extraction three times. Add 8 times the amount of ethanol for the first extraction, and add 6 times the amount of ethanol for the second and third extractions. Each extraction lasts for 1 hour. Combine the extracts and filter to obtain a mixed extract 1.

[0101] (4) decocting and extracting Scutellaria baicalensis for 3 times, adding 8 times the amount of ethanol for the first time, and adding 6 times the amount of ethanol for the second and third times, each extraction for 1 hour, filtering the decoction, combining the filtrate, and obtaining the Scutellaria baicalensis decoction; concentrating the Scutellaria baicalensis decoction to a relative density of 1.10-1.20, adjusting the pH value to 2.0, standing for 3 hours, and centrifuging to obtain a crude extract, washing the crude extract to a pH value of 4.0, drying to a moisture content of no more than 5.0%, and crushing to obtain a fine powder of Scutellaria baicalensis extract;

[0102] (5) Decoction the earthworm, mulberry bark, and lily of the valley with water for two times: add 15 times the amount of water for the first time and decoct for 20 min; add 10 times the amount of water for the second time and decoct for 15 min. Combine the decoctions and filter to obtain a mixed extract 2;

[0103] (6) mixing the Fritillaria percolate, gypsum decoction, mixed extract 1, and mixed extract 2, and performing double-effect concentration to obtain a clear paste;

[0104] The conditions for double-effect concentration are: steam pressure: 0.1MPa; vacuum degree of the first effect: -0.05~-0.1MPa, concentration temperature of the first effect: 70°C; vacuum degree of the second effect: -0.05~-0.1MPa, concentration temperature of the second effect: 60°C. The relative density of the final clear paste is 1.20 (50-60°C).

[0105] (7) The paste obtained in step (6) is mixed with the fine powder of the scutellaria baicalensis extract obtained in step (4) to obtain the composition having the effect of relieving cough.

[0106] Comparative Example 5

[0107] The difference from Example 1 is that in step (6), evaporation is used to concentrate the solution to a relative density of 1.20 (50-60° C.). The other conditions are the same.

[0108] Results

[0109] 1. Determination of effective ingredient transfer rate

[0110] The total flavonoid content before and after is measured by the same method to calculate the total flavonoid transfer rate. As an example, the total flavonoid content is measured by spectrophotometry before and after in the present invention.

[0111] (1) Determine the sum of the total flavonoids content (M1) in the Fritillaria percolate, gypsum decoction, mixed extract 1, and mixed extract 2 obtained in Example 1-3, determine the total flavonoids content (M2) in the clear paste obtained in step (6) of Example 1-3, and calculate the transfer rate:

[0112] Transfer rate = M2 / M1×100%.

[0113] (2) The transfer rate of comparative example 1 is the ratio of the total flavonoid content in the clear paste obtained in step (4) to the total flavonoid content in the filtrate obtained in step (4).

[0114] (3) The transfer rate calculation method of Comparative Example 2 is the same as that of Examples 1-3, except that the Fritillaria percolate solution is replaced by the Fritillaria decoction solution.

[0115] (4) Determine the sum of the total flavonoids content (A1) in the Fritillaria percolate, gypsum decoction, mixed extract 1, and mixed extract 2 obtained in Comparative Example 3, and determine the sum of the total flavonoids content (A2) in the clear paste 1, clear paste 2, clear paste 3, and clear paste 4 of Comparative Example 3, and calculate the transfer rate:

[0116] Transfer rate = A2 / A1×100%.

[0117] (5) The transfer rate calculation method of Comparative Examples 4 and 5 is the same as that of Examples 1-3.

[0118] Test results:

[0119]

[0120]

[0121] The results show that the extraction process of the present invention significantly improves the transfer rate of total flavonoids. In particular, the results of Example 1 and Comparative Example 3 show that extracting each component separately and then mixing and concentrating is beneficial to maintaining the stability of total flavonoids in the mixed extract and reducing the loss of effective ingredients.

[0122] 2. The therapeutic effect of the composition of the present invention on mice with acute bronchitis

[0123] Modeling: Mice (male Kunming mice, weighing 18-22g) were adaptively raised for one week, and then the mice in the experimental group were placed in a 100cm×100cm×50cm smoke chamber and smoked with 20 cigarettes for 30 minutes, twice a day for 2 weeks to obtain acute bronchitis model mice. The blank group was raised normally.

[0124] Experiment and administration: After two weeks, the model mice were randomly divided into groups, with 10 mice in each group, and the pharmaceutical compositions of Examples 1-3 and Comparative Examples 1-5 (dosage 1g / Kg) and Jizhi Syrup (Taiji, dosing 20mL / kg) were respectively administered by gavage once a day, and the model group and the blank group were gavaged with the same volume of normal saline. The administration was continued for one week. One hour after the last administration, blood was collected from the eye sockets of mice in each group, centrifuged at 2000rpm for 25min at room temperature, and serum was separated. The content of IL-6, IL-8, and TNF-a was determined by Elisa method. The results are as follows:

[0125] IL-6 (pg / mL) IL-8 (pg / mL) TNF-a (pg / mL) Blank group 82.5±3.47 492.3±9.78 64.2±6.11 Model Group 159.1±4.76*** 901.8±11.04*** 122.0±5.79*** Acute syrup group 89.9±2.54### 671.8±15.75## 70.5±4.34## Example 1 87.4±6.75### 624.4±13.55## 65.8±4.87### Example 2 90.1±5.88### 640.2±14.41## 71.7±5.10## Example 3 86.1±4.51### 637.8±10.57## 69.0±6.54## Comparative Example 1 101.3±7.20##△△ 723.4±14.33##△△ 84.9±3.13##△△ Comparative Example 2 96.4±3.45##△ 698.3±12.14##△ 80.7±8.32##△ Comparative Example 3 99.5±3.94##△△ 705.6±13.87##△△ 77.1±7.58## Comparative Example 4 114.6±5.36##△△ 750.4±15.51##△△ 91.5±5.08##△△ Comparative Example 5 98.7±2.41##△ 686.6±12.72##△ 81.6±4.33##△

[0126] Note: Compared with the blank group, **P<0.01; ***P<0.001; compared with the model group, #P<0.01; ##P<0.05; ###P<0.001; compared with the comparative examples 1-5 and Example 1, △ P<0.01; △△P<0.05; △△△P<0.001.

[0127] The results show that the compositions of Examples 1-3 and Comparative Examples 1-5 of the present invention can significantly reduce the content of IL-6, IL-8, and TNF-a in the serum of model mice, among which the effect of Examples 1-3 is significantly better than that of Comparative Examples 1-5, and is equivalent to that of the acute bronchitis syrup. In summary, the composition prepared by the preparation process of the present invention significantly improves the therapeutic effect on acute bronchitis by optimizing the process.

[0128] 2. Antitussive effect of the composition of the present invention

[0129] Modeling: Mice (male Kunming mice, weighing 18-22g) were adaptively raised for one week and randomly divided into groups of 10 mice in each group. They were given the pharmaceutical compositions of Examples 1-3 and Comparative Examples 1-5 (dosage 1g / Kg) respectively, and were gavaged once a day. The blank group was gavaged with an equal volume of normal saline. The administration was continued for 3 days. One hour after the last administration, the mice were placed in an inverted 1L glass beaker with 100mg sterilized cotton balls (0.5mL ammonia water was injected in advance) in the glass beaker. The latency time of the mouse cough (the time from the beaker being buckled to the first cough) and the number of coughs within 3 minutes were recorded. The cough was defined by the violent contraction of the mouse abdominal muscles and the opening of the mouth. The results are as follows:

[0130] Cough latency time (s) Number of coughs within 3 minutes (times) Blank group 21.24±7.67 62.5±15.44 Example 1 85.77±10.51*** 15.4±9.55*** Example 2 82.52±6.04*** 19.7±10.27*** Example 3 79.15±15.74*** 21.2±15.89*** Comparative Example 1 56.31±8.57**△△ 36.2±18.44**△△ Comparative Example 2 69.42±6.81***△ 27.1±12.17***△ Comparative Example 3 64.68±11.74***△ 29.6±14.78***△ Comparative Example 4 45.09±8.75**△△ 34.8±15.70**△△ Comparative Example 5 59.45±7.63***△△ 31.3±13.15**△

[0131] Note: Compared with the blank group, *P<0.05; **P<0.01; ***P<0.001; Compared with Example 1, △ P < 0.01; △△ P < 0.05; △△△P<0.001.

[0132] The results show that the compositions of Examples 1-3 and Comparative Examples 1-5 of the present invention can significantly prolong the latent time of cough and relieve the frequency of cough in mice. The effect of Examples 1-3 is significantly better than that of Comparative Examples 1-5. The above results show that the composition prepared by the preparation process of the present invention has a good therapeutic effect on cough.

[0133] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing a composition having a cough relieving effect, characterized in that: The steps include: (1) crushing Fritillaria to obtain Fritillaria fine powder, soaking it in ethanol, and extracting it by percolation to obtain Fritillaria percolate; (2) gypsum is boiled in water for 1-3 times, the decoctions are combined and filtered to obtain gypsum decoction; (3) Grind bitter almonds, pinellia tuber, and ginkgo kernel, put them in a decoction bag, and combine them with ephedra, earthworm, mulberry bark, lily, licorice, perilla seed, and scutellaria baicalensis seed, add ethanol, heat and reflux for extraction 2-4 times, and combine the extracts to obtain a mixed extract 1; (4) decoct the Scutellaria baicalensis for 2-5 times, filter the decoction, combine the filtrate, and obtain the Scutellaria baicalensis decoction; concentrate the Scutellaria baicalensis decoction, adjust the pH value to 1.5-2.5, let it stand for 1-5 hours, centrifuge to obtain a crude extract, wash the crude extract until the pH value reaches 3.5-4.5, dry, and crush to obtain a fine powder of the Scutellaria baicalensis extract; (5) decoct honeysuckle and coltsfoot flowers in water for 1-3 times, combine the decoctions, filter, and obtain mixed extract 2; (6) Mix the Fritillaria percolate, gypsum decoction, mixed extract 1, and mixed extract 2, and concentrate to obtain a clear paste; (7) The paste obtained in step (6) is mixed with the fine powder of the scutellaria baicalensis extract obtained in step (4) to obtain the composition having the effect of relieving cough.

2. The preparation method according to claim 1, characterized in that: In the preparation method, the formula of the Chinese medicine composition is: 110-125 parts by weight of honey ephedra, 110-125 parts by weight of mulberry bark, 225-240 parts by weight of honeysuckle, 110-125 parts by weight of scutellaria, 205-220 parts by weight of celery, 205-220 parts by weight of gypsum, 110-125 parts by weight of thunbergia thunbergii, 110-125 parts by weight of bitter almond, 110-125 parts by weight of perilla seed, 110-125 parts by weight of coltsfoot flower, 110-125 parts by weight of scutellaria baicalensis, 205-220 parts by weight of earthworm, 75-90 parts by weight of pinellia ternata, 110-125 parts by weight of stir-fried ginkgo nuts, and 75-90 parts by weight of roasted liquorice.

3. The preparation method according to any one of claims 1 to 2, characterized in that: In step (1), the ethanol refers to an ethanol aqueous solution, wherein the volume concentration of ethanol is 60-80%; In step (1), the mass of the ethanol is 5-15 times the mass of the Fritillaria, the infiltration time is 6-12 hours, and the percolation extraction rate is 1-5 mL / kg / min; In step (2), the decoction extraction is performed twice, 4-6 times the weight of water is added each time, and the decoction extraction time is 0.5-1h each time; In step (3), the ethanol refers to an ethanol aqueous solution, wherein the volume concentration of ethanol is 35-45%; In step (3), the heating reflux extraction is performed three times, preferably: 6-10 times the amount of ethanol is added in the first time, and 4-8 times the amount of ethanol is added in the second and third times, and each extraction is performed for 0.5-1.5 hours.

4. The preparation method according to any one of claims 1 to 2, characterized in that: Step (4) is specifically as follows: decocting and extracting Scutellaria baicalensis for 3 times, adding 8 times the amount of ethanol for the first time, and adding 6 times the amount of ethanol for the second and third times, each extraction for 1 hour, filtering the decoction, combining the filtrate, and obtaining the Scutellaria baicalensis decoction; concentrating the Scutellaria baicalensis decoction, adjusting the pH value to 2.0, standing for 3 hours, centrifuging to obtain a crude extract, washing the crude extract until the pH value reaches 4.0, drying, and crushing to obtain a fine powder of Scutellaria baicalensis extract.

5. The preparation method according to any one of claims 1 to 2, characterized in that: In step (5), the decoction is performed twice; preferably, 15-20 times the amount of water is added for the first time and the decoction is performed for 15-25 minutes; and 8-12 times the amount of water is added for the second time and the decoction is performed for 10-20 minutes.

6. The preparation method according to any one of claims 1-2, characterized in that: In step (6), the concentration is double-effect concentration, and the conditions of double-effect concentration are: steam pressure: 0.1 to 0.2 MPa; first-effect vacuum degree: -0.05 to -0.1 MPa, first-effect concentration temperature: 60 to 80°C; second-effect vacuum degree: -0.05 to -0.1 MPa, second-effect concentration temperature: 50 to 70°C; relative density of the clear paste obtained by concentration: 1.15 to 1.

25.

7. A composition with antitussive effect prepared by the preparation method according to any one of claims 1 to 6.

8. Use of the composition with antitussive effect according to claim 7 in the preparation of a drug for treating antitussive.

9. The use according to claim 8, characterized in that: The cough-relieving drug is used to clear the lungs and resolve phlegm, relieve cough and asthma, and is used for acute bronchitis and acute attacks of chronic bronchitis, which are caused by phlegm-heat stagnation in the lungs, with symptoms such as cough, wheezing, yellow or thick phlegm, fever, dry mouth, yellow and greasy tongue coating, and red tongue.

10. A drug, characterized in that The effective ingredients thereof include the composition with antitussive effect as claimed in claim 7.

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