Chinese and western medicine composition for treating wind-heat type common cold as well as preparation method and application of Chinese and western medicine composition

Abstract

The invention relates to the technical field of traditional Chinese medicine, in particular to a Chinese and western medicine composition for treating wind-heat type common cold and a preparation method and application thereof. The traditional Chinese and western medicine composition comprises the following components in parts by weight: 4-8 parts of a traditional Chinese medicine extract A; 3-7 parts of a traditional Chinese medicine extract B; 5-10 parts of a traditional Chinese medicine extract C; 1-5 parts of a western medicine composition D; the traditional Chinese medicine extract A is prepared by performing CO2 supercritical extraction and volatile oil clathration on honeysuckle; the traditional Chinese medicine extract B is obtained by carrying out enzymolysis on honeysuckle and isatis root; the traditional Chinese medicine extract C is prepared from honeysuckle and radix isatidis through ultrasonic extraction; the western medicine composition D is prepared from raw material components including calculus bovis factitius, acetaminophen and amantadine hydrochloride. The Chinese and western medicine composition is simple in component, can enhance the anti-inflammatory, cough-relieving and phlegm-eliminating effects, and obviously improves various symptoms caused by cold.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and in particular to a Chinese and Western medicine composition for treating wind-heat cold, a preparation method and application thereof. Background Art

[0002] Colds are common illnesses that, if left untreated, can lead to complications and be life-threatening. Colds are categorized by their symptoms as wind-cold and wind-heat. Wind-heat is the most common, with symptoms including fever, dry throat and mouth, runny nose, yellow phlegm, and headache. Symptomatic treatment can cure the condition. However, severe or worsening symptoms can trigger pre-existing conditions or comorbidities, potentially leading to secondary bacterial infections and severely impacting normal life and health. Therefore, appropriate medications should be selected to treat this condition.

[0003] Currently, colds are mostly treated with traditional Chinese medicine (TCM) or Western medicine, each with its own distinct focus. TCM emphasizes syndrome differentiation and treatment, but its effectiveness is slow. Western medicine, on the other hand, focuses on rapid relief of cold symptoms, but its effectiveness is short-lived and prone to relapse. Therefore, developing a new TCM and Western medicine treatment for wind-heat colds is a common goal for medical professionals.

[0004] Patent application document CN106138259A discloses a traditional Chinese medicine composition for treating wind-heat cold and its preparation method, which is prepared from the following raw medicinal materials in the following weight ratio: 1-3 parts of bupleurum, 2-4 parts of kudzu root, 1-3 parts of scutellaria, 3-5 parts of gypsum, 2-4 parts of artemisia annua, 1-3 parts of white peony root, and 0-2 parts of roasted licorice.

[0005] Patent application document CN105194633A discloses a compound preparation of Chinese and Western medicine for treating colds. The raw materials, in parts by weight, include: 5-9 parts of honeysuckle, 6-8 parts of dried ginger, 4-6 parts of white peony root, 4-6 parts of angelica dahurica, 5-8 parts of burdock fruit, 5-8 parts of herba rutaecarpa, 6-8 parts of bayberry, 6-8 parts of citrus aurantium, 4-6 parts of perilla leaf, 3-5 parts of lobelia, 3-5 parts of hawthorn, 3-5 parts of bupleurum, 0.5-1 part of acetaminophen, 0.01-0.02 parts of chlorpheniramine maleate, and 0.01-0.02 parts of caffeine.

[0006] Patent application document CN107669780A discloses a Ganmaoling granule and a preparation method thereof, which is prepared from the following raw medicinal materials in the following weight ratio: 450-530 parts of Tripterygium wilfordii, 300-350 parts of Calendula officinalis, 200-300 parts of Chrysanthemum indicum, 700-780 parts of Prunus mume, 15-25 parts of acetaminophen, 0.1-0.7 parts of chlorpheniramine maleate, 0.2-0.6 parts of caffeine, 0.1-0.3 parts of peppermint oil, 200-300 parts of lactose, 100-200 parts of debranched starch, 60-120 parts of microcrystalline cellulose, 5-10 parts of β-cyclodextrin, 3-5 parts of polyvinylpyrrolidone and 80-120 parts of ethanol.

[0007] There are many such pharmaceutical compositions for treating colds, but they all have more or less disadvantages, such as too many medicinal flavors, large dosage, unclear active ingredients, rough preparation process, backward technology, slow onset of effect, low bioavailability, and efficacy that needs to be improved. Summary of the Invention

[0008] In view of this, the technical problem to be solved by the present invention is to provide a Chinese and Western medicine composition for treating wind-heat cold, its preparation method and application, which has simple components, can enhance the anti-inflammatory, antitussive and expectorant effects, and significantly improve various symptoms caused by colds.

[0009] In view of the shortcomings of the existing technology, the present invention uses honeysuckle, isatis root, artificial bezoar, acetaminophen and amantadine hydrochloride as main raw materials, extracts, separates and combines the effective ingredients through modern scientific technology to obtain effective extracts and Western medicine compositions. Through corresponding proportions, the therapeutic effects are exerted. Pharmacodynamic studies have shown that the extracts have the effect of significantly reducing acute inflammation in mice, removing phlegm and relieving cough, thereby achieving the effect of treating wind-heat colds.

[0010] The Chinese and Western medicine composition of the present invention exerts its effects through mechanisms such as antiviral, antipyretic and analgesic, anti-inflammatory, immunomodulatory, and antiallergic effects. Among them, amantadine hydrochloride has an anti-influenza A virus effect and can be used for the prevention and treatment of influenza. Acetaminophen can reduce body temperature and relieve pain by inhibiting prostaglandin synthesis. Artificial bezoar has the effects of clearing heat, detoxifying, expectorant, anti-inflammatory, and calming the nerves. It is used for delirium caused by heat phlegm, coma and aphasia, acute febrile convulsions in children, sore throat, etc. Honeysuckle mainly contains effective ingredients such as chlorogenic acid, isochlorogenic acid, and luteolin, which have the effects of clearing heat and detoxifying, and evacuating wind-heat. In addition, honeysuckle has a certain inhibitory effect on various pathogenic bacteria, such as pneumococcus, Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. Isatis root has the effects of clearing heat and detoxifying, cooling blood and relieving sore throats, and reducing swelling. It can inhibit the replication of various viruses, including influenza viruses and coronaviruses. It is commonly used to treat tonsillitis and sore throats. Isatis root can exert its therapeutic effects by inhibiting viral replication and regulating the immune system. By combining these drugs to form a clear composition, it can enhance anti-inflammatory, antitussive, and expectorant effects, significantly improving various symptoms caused by colds.

[0011] The present invention provides a Chinese and Western medicine composition for treating wind-heat cold, comprising, by weight:

[0012]

[0013]

[0014] The Chinese medicine extract A is prepared by CO2 supercritical extraction and volatile oil inclusion of honeysuckle;

[0015] The Chinese medicine extract B is obtained by enzymatic hydrolysis of honeysuckle and isatis root;

[0016] The Chinese medicine extract C is prepared by ultrasonic extraction of honeysuckle and isatis root;

[0017] The western medicine composition D is prepared from raw material components including artificial bezoar, acetaminophen and amantadine hydrochloride.

[0018] In some embodiments of the present invention, the weight proportions of the Chinese herbal extract A are 4 parts, 6 parts, 8 parts, 12 parts, 10 parts, or 3 parts.

[0019] In some embodiments of the present invention, the weight parts of the traditional Chinese medicine extract B are 3 parts, 5 parts, 7 parts, 9 parts, 2 parts, and 10 parts.

[0020] In some embodiments of the present invention, the weight proportions of the Chinese herbal extract C are 5 parts, 7 parts, 10 parts, 4 parts, 12 parts, or 3 parts.

[0021] In some embodiments of the present invention, the weight parts of the western medicine composition D are 1 part, 3 parts, 5 parts, 6 parts, 2 parts, and 7 parts.

[0022] Preferably, the Chinese and Western medicine composition comprises, by weight:

[0023]

[0024] The Chinese medicine extract A is prepared by CO2 supercritical extraction and volatile oil inclusion from honeysuckle, wherein the volatile oil inclusion material is β-cyclodextrin.

[0025] In some embodiments of the present invention, the preparation method of the traditional Chinese medicine extract A comprises the following steps:

[0026] a1) crushing the honeysuckle and performing CO2 supercritical extraction;

[0027] a2) separating the components after the CO2 supercritical extraction to obtain volatile oil;

[0028] a3) dissolving the volatile oil in ethanol and adding the solution dropwise to a β-cyclodextrin aqueous solution for volatile oil inclusion to obtain a volatile oil inclusion complex, namely, the Chinese herbal extract A.

[0029] Regarding step a1):

[0030] After the honeysuckle is crushed, it is subjected to CO2 supercritical extraction.

[0031] Grind the honeysuckle into 50 mesh fine powder.

[0032] The CO2 supercritical extraction is carried out in a CO2 supercritical extraction kettle with a pressure of 40-45 MPa, such as 42 MPa, a temperature of 55-60°C, such as 55°C, and a time of 120-180 min, such as 150 min.

[0033] In the CO2 supercritical extraction, the CO2 flow rate is 20-25 kg / h, such as 22 kg / h.

[0034] Regarding step a2):

[0035] The components after the CO2 supercritical extraction are separated to obtain volatile oil.

[0036] The separation process comprises two stages: the primary separation is performed in separation vessel I, and the secondary separation is performed in separation vessel II. The primary separation vessel pressure is 9-12 MPa, for example, 10 MPa, and the temperature is 40-45°C, for example, 42°C. The high-boiling-point components are separated at high pressure. The secondary separation vessel pressure is 6-8 MPa, for example, 7 MPa, and the temperature is 40-45°C, for example, 42°C. The light volatile oil is collected at low pressure.

[0037] Regarding step a3):

[0038] The volatile oil is dissolved in ethanol and then added dropwise to a β-cyclodextrin aqueous solution for volatile oil inclusion to obtain a volatile oil inclusion compound, which is the traditional Chinese medicine extract A.

[0039] Specifically include:

[0040] The volatile oil is dissolved in ethanol and then added dropwise to a β-cyclodextrin aqueous solution. The mixture is stirred at 35-45° C., refrigerated at 5-10° C., and centrifuged. The obtained precipitate is vacuum dried to obtain a volatile oil inclusion compound.

[0041] The mass of the ethanol is 1 to 3 times, such as 1.5 times, the volume of the volatile oil.

[0042] The ratio of the volatile oil to β-cyclodextrin is 0.5-1.5 mL: 6-7 g, such as 1 mL: 6.5 g. The mass concentration of the β-cyclodextrin aqueous solution is 12%-15%, such as 13.5%.

[0043] The stirring and mixing time at 35-45° C. is 3-7 hours, for example, 5 hours. The stirring and mixing temperature can specifically be 40° C.

[0044] The refrigeration time at 5-10°C is 22-26 hours, for example, 24 hours. The specific refrigeration temperature is 8°C.

[0045] The vacuum drying temperature is 35-45° C., such as 40° C., and the drying time is 3-7 hours, such as 5 hours.

[0046] After obtaining the volatile oil inclusion compound, the method further comprises: grinding the volatile oil inclusion compound into fine powder, wherein the particle size of the fine powder does not exceed 200 mesh, for example, 150 mesh.

[0047] The Chinese herbal extract B is obtained by enzymatic hydrolysis of honeysuckle and isatis root. The enzymatic hydrolysis employs a complex enzyme comprising cellulase and pectinase in a mass ratio of 0.5-1.5:1-2, for example, 1:1.5. The Chinese herbal extract B primarily comprises organic acids and polysaccharides.

[0048] In some embodiments of the present invention, the preparation method of the traditional Chinese medicine extract B comprises the following steps:

[0049] b1) crushing honeysuckle and slicing isatis root, decocting with water under the action of a complex enzyme, and reflux extraction to obtain an extract;

[0050] b2) filtering the extract, concentrating the obtained filtrate into a clear paste, adding ethanol, allowing the mixture to settle, and filtering to obtain a supernatant and a precipitate;

[0051] b3) mixing the precipitate with aqueous hydrochloric acid solution, adjusting the pH value to 6-7, dissolving with ethanol, filtering, combining the obtained filtrate with the supernatant, concentrating, and purifying with an LS-303 macroporous resin column to obtain a Chinese herbal extract B.

[0052] Regarding step b1):

[0053] The honeysuckle is crushed, the isatis root is sliced, and the mixture is decocted with water under the action of a complex enzyme, and refluxed for extraction to obtain an extract.

[0054] The mass ratio of honeysuckle and isatis root is 10-15:5-10, such as 12:8.

[0055] Grind the honeysuckle and pass through a 20-mesh sieve.

[0056] Cut the isatis root into 2-3 mm thin slices.

[0057] Under the action of complex enzyme, water is added for decoction and reflux extraction is performed to obtain an extract, specifically:

[0058] b1-1) first add water and complex enzyme to decoct, and reflux extraction;

[0059] b1-2) Add water and reflux to extract, and combine the extracts.

[0060] b1-1) In:

[0061] The mass of the water is 8 to 12 times, for example, 10 times, the mass of the medicinal materials (honeysuckle and isatis root). The mass of the complex enzyme is 1% to 3%, for example, 2.5% of the mass of the medicinal materials (honeysuckle and isatis root).

[0062] The decoction temperature is 45-55° C., such as 50° C., and the decoction time is 55-65 min, such as 60 min.

[0063] The reflux extraction time is 1.8 to 2.2 hours, such as 2 hours.

[0064] b1-2) In:

[0065] The mass of water is 6 to 10 times the mass of the medicinal materials (honeysuckle and isatis root), for example, 8 times.

[0066] The reflux extraction time is 0.8 to 1.2 hours, such as 1 hour.

[0067] Regarding step b2):

[0068] The extract is filtered, and the obtained filtrate is concentrated into a clear paste, ethanol is added, and the mixture is allowed to stand for precipitation, and filtered to obtain a supernatant and a precipitate.

[0069] The relative density of the clear paste at 60° C. is 1.21 to 1.25, for example, 1.25.

[0070] After adding ethanol, the alcohol content of the clear paste is 65 wt % to 75 wt %, for example 70 wt %.

[0071] The settling time is 22 to 26 hours, for example, 24 hours.

[0072] Regarding step b3):

[0073] The precipitate was mixed with a hydrochloric acid aqueous solution, the pH value was adjusted to 6-7, ethanol was added to dissolve, and the mixture was filtered. The obtained filtrate was combined with the supernatant, concentrated, and purified using an LS-303 macroporous resin column to obtain a traditional Chinese medicine extract B.

[0074] The mass ratio of the precipitate to the hydrochloric acid aqueous solution is 1:7-9, such as 1:8. The mass concentration of the hydrochloric acid aqueous solution is 1.5%-2.5%, such as 2%.

[0075] The reagent used to adjust the pH value is NaOH solution with a mass concentration of 2.5% to 3.5%, for example, 3%. The pH value is adjusted to 6.5.

[0076] Add ethanol so that the alcohol content of the solution is 68 wt% to 72 wt%, for example 70 wt%, and dissolve the solution by stirring.

[0077] The concentration is performed to a solid-liquid ratio of 1:3.5 to 4.5, such as 1:4.

[0078] Purification was performed using LS-303 macroporous resin column, specifically:

[0079] Use LS-303 macroporous resin column, elute with water, discard the water washing liquid, then elute with 50% ethanol and 30% ethanol in sequence, collect the ethanol eluate, and recover until there is no alcohol smell.

[0080] The amount of water used for elution is 4.5 to 5.5 times the column volume, specifically 5 times.

[0081] The dosage of the ethanol with a mass concentration of 50% is 6.5 to 7.5 times the column volume, specifically 7 times.

[0082] The amount of ethanol with a mass concentration of 30% is 4.5 to 5.5 times the column volume, specifically 5 times.

[0083] After the purification, the process further includes freeze drying and pulverizing into fine powder, wherein the particle size of the fine powder does not exceed 200 meshes.

[0084] The Chinese herbal medicine extract C is prepared by ultrasonic extraction of honeysuckle and isatis root. The Chinese herbal medicine extract C mainly contains flavonoids and alkaloids.

[0085] In some embodiments of the present invention, the preparation method of the Chinese medicine extract C comprises the following steps:

[0086] c1) crushing the honeysuckle and isatis root, and ultrasonically extracting them with an ethanol solution to obtain an ultrasonic extract;

[0087] c2) filtering, recovering ethanol, and concentrating the liquid medicine;

[0088] c3) purifying the medicinal solution using an AB-8 macroporous resin column to obtain a Chinese herbal medicine extract C.

[0089] Regarding step c1):

[0090] The honeysuckle and isatis root are crushed, and ultrasonic extraction is performed using an ethanol solution to obtain an ultrasonic extract.

[0091] The mass ratio of honeysuckle and isatis root is 8-13:12-18, such as 10:15.

[0092] The powder was sieved through a 20-mesh sieve.

[0093] The mass concentration of the ethanol solution is 75% to 85%, for example, 80%. The number of ultrasonic extractions is 2 times. Specifically:

[0094] The mass of the ethanol solution used in the first ultrasonic extraction is 13 to 17 times, for example, 15 times, the mass of the medicinal materials (honeysuckle and isatis root). The time for the first ultrasonic extraction is 50 to 70 minutes, for example, 60 minutes.

[0095] The mass of the ethanol solution used in the second ultrasonic extraction is 10 to 14 times, for example 12 times, the mass of the medicinal materials (honeysuckle and isatis root). The time for the second ultrasonic extraction is 50 to 70 minutes, for example 60 minutes.

[0096] Combine the ultrasonic extracts from the two ultrasonic treatments.

[0097] Regarding step c2):

[0098] Filter, recover ethanol, and concentrate the liquid medicine.

[0099] The concentration of the crude drug in the drug solution is concentrated to 0.3-0.7 g / mL, such as 0.5 g / mL.

[0100] Regarding step c3):

[0101] The medicinal solution was purified using an AB-8 macroporous resin column to obtain a traditional Chinese medicine extract C.

[0102] The purification steps are specifically as follows:

[0103] An AB-8 macroporous resin column was used for elution with ethanol, the eluate was collected, the ethanol was recovered, and the extract was concentrated to obtain the Chinese medicine extract C.

[0104] Prior to elution with ethanol, the AB-8 macroporous resin column is further subjected to impurity removal. Specifically, water and ethanol are sequentially used for impurity removal. The amount of water used is 2 to 4 column volumes, for example, 3 column volumes. The amount of ethanol used is 2 to 4 column volumes, for example, 3 column volumes. The mass concentration of the ethanol is 8% to 12%, for example, 10%.

[0105] The mass concentration of ethanol used for elution is 45% to 55%, such as 50%. The amount of ethanol used for elution is 6 to 8 times the column volume, such as 7 times the column volume.

[0106] The concentration is performed under reduced pressure, and the temperature for the concentration is 55-65° C., such as 60° C. The relative density of the extract is 1.15-1.20, such as 1.18.

[0107] After obtaining the extract, freeze-drying is also included.

[0108] In the present invention, the western medicine composition D is prepared from raw material components including artificial bezoar, acetaminophen and amantadine hydrochloride.

[0109] The mass ratio of the artificial bezoar, acetaminophen and amantadine hydrochloride is 0.5-1.5:13-17:3-7, for example 1:15:5.

[0110] In some embodiments of the present invention, the preparation method of the western medicine composition D comprises the following steps:

[0111] d1) dissolving acetaminophen in ethanol and adding the solution dropwise to the hydroxypropyl β-cyclodextrin aqueous solution, stirring and mixing, refrigerating, centrifuging, and vacuum drying the resulting precipitate to obtain an acetaminophen inclusion complex;

[0112] d2) Grinding the acetaminophen inclusion compound into fine powder, and mixing it with amantadine hydrochloride and artificial bezoar to obtain a western medicine composition D.

[0113] Regarding step d1):

[0114] After dissolving acetaminophen in ethanol, the solution was added dropwise to a hydroxypropyl β-cyclodextrin aqueous solution, stirred and mixed, refrigerated, and centrifuged. The obtained precipitate was vacuum dried to obtain an acetaminophen inclusion compound.

[0115] The mass ratio of acetaminophen to ethanol is 0.8-1.2:0.8-1.2, for example 1:1.

[0116] The mass concentration of the hydroxypropyl β-cyclodextrin aqueous solution is 12% to 15%, such as 13.5%.

[0117] The stirring and mixing is performed at a temperature of 35 to 45° C., such as 40° C., and for a time of 4 to 6 hours, such as 5 hours.

[0118] The refrigeration temperature is 6-10° C., such as 8° C.; the refrigeration time is 22-26 hours, such as 24 hours.

[0119] The vacuum drying temperature is 35-45° C., such as 40° C., and the drying time is 4-6 hours, such as 5 hours.

[0120] Regarding step d2):

[0121] The acetaminophen inclusion compound is crushed into fine powder, and mixed with amantadine hydrochloride and artificial bezoar to obtain a western medicine composition D.

[0122] The particle size of the fine powder does not exceed 200 mesh.

[0123] In some embodiments of the present invention, in the Chinese and western medicine composition, the weight proportion of the Chinese medicine extract A is 6 parts.

[0124] In some embodiments of the present invention, in the Chinese and western medicine composition, the weight proportion of the Chinese medicine extract B is 7 parts.

[0125] In some embodiments of the present invention, in the Chinese and western medicine composition, the weight proportion of the Chinese medicine extract C is 5 parts.

[0126] In some embodiments of the present invention, in the Chinese and western medicine composition, the weight proportion of the western medicine composition D is 3 parts.

[0127] The present invention also provides a method for preparing the above-mentioned Chinese and Western medicine composition, comprising the following steps:

[0128] The Chinese medicine extract A, the Chinese medicine extract B, the Chinese medicine extract C and the western medicine composition D are mixed to obtain a Chinese and western medicine composition.

[0129] The present invention also provides a use of the above-mentioned Chinese and Western medicine combination in the preparation of a medicine for preventing or treating wind-heat cold.

[0130] The present invention also provides a use of the above-mentioned Chinese and Western medicine combination in the preparation of anti-inflammatory drugs.

[0131] The present invention also provides a use of the above-mentioned Chinese and Western medicine combination in preparing cough suppressant medicine.

[0132] The present invention also provides a pharmaceutical preparation, which is composed of the above-mentioned Chinese and Western medicine combination and pharmaceutically acceptable excipients.

[0133] In some embodiments of the present invention, the dosage form of the pharmaceutical preparation is a mixture, syrup, tablet, granule or capsule.

[0134] The present invention has no particular limitation on the raw material components used above, and they can be commonly available on the market.

[0135] The present invention uses scientific and technological methods and instruments to separate and purify the effective ingredients of different medicinal flavors, make reasonable proportions, and verify them through pharmacodynamic experiments. The results show that the obtained Chinese and Western medicine combination can effectively treat symptoms such as nasal congestion, sore throat, cough, and yellow sputum caused by wind-heat cold. DETAILED DESCRIPTION

[0136] The following will clearly and completely describe the technical solutions of the present invention in conjunction with the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0137] Preparation of Chinese herbal medicine extract A:

[0138] Take 10 parts by weight of honeysuckle, crush it into 50 mesh fine powder, put it into a carbon dioxide supercritical extraction kettle, and perform CO2 supercritical extraction at a pressure of 42 MPa, a temperature of 55°C, and a time of 150 min; the CO2 flow rate is 22 kg / h;

[0139] The components after the CO2 supercritical extraction are separated, and the separation includes two-stage separation: the first stage separation is carried out in separation kettle I, and the second stage separation is carried out in separation kettle II; the pressure of separation kettle I is 10MPa and the temperature is 42°C; the pressure of separation kettle II is 7MPa and the temperature is 42°C; volatile oil is collected from separation kettles I and II;

[0140] The volatile oil was dissolved in ethanol (the mass of the ethanol was 1.5 times the volume of the volatile oil) and added dropwise to a β-cyclodextrin aqueous solution with a mass concentration of 13.5% (the ratio of the volatile oil to β-cyclodextrin was 1 mL:6.5 g). The mixture was stirred at 40° C. for 5 h, refrigerated at 8° C. for 24 h, and centrifuged to obtain a precipitate. The precipitate was vacuum-dried at 40° C. for 5 h to obtain a volatile oil inclusion complex, which was pulverized into a fine powder (particle size not exceeding 150 mesh) to obtain a traditional Chinese medicine extract A with heat-clearing and detoxifying effects.

[0141] Preparation of Chinese herbal medicine extract B:

[0142] Take 12 parts by weight of honeysuckle and 8 parts by weight of isatis root, crush the honeysuckle and pass it through a 20-mesh sieve, cut the isatis root into 2-3 mm slices, add water for the first time (the mass of the water is 10 times the mass of the medicinal materials (honeysuckle and isatis root)), then add a complex enzyme (the complex enzyme is cellulase and pectinase; the mass ratio is 1:1.5), and the mass of the complex enzyme is 2.5% of the mass of the medicinal materials (honeysuckle and isatis root); maintain a constant temperature of 50°C for enzymolysis for 60 minutes, reflux extraction for 2 hours, add water for the second time (the mass of the water is 8 times the mass of the medicinal materials (honeysuckle and isatis root)), reflux extraction for 1 hour, combine the extracts, filter, and concentrate the filtrate to a clear paste with a relative density of 1.25 (60°C), add ethanol to make the alcohol content of the clear paste 70wt%, let it stand for 24 hours to precipitate, filter, and obtain a supernatant and a precipitate;

[0143] The precipitate is mixed with a 2% hydrochloric acid aqueous solution in a mass ratio of 1:8, and then a 3% NaOH solution is used to adjust the pH value to 6.5, and ethanol is added to make the alcohol content 70wt%, and the mixture is stirred and dissolved. The mixture is filtered, and the obtained filtrate is combined with the supernatant and concentrated to a material-liquid ratio of 1:4. An LS-303 macroporous resin column is used for elution with 5 times the column volume of water, and the water washing liquid is discarded. The mixture is then eluted with 7 times the column volume of 50% ethanol and 5 times the column volume of 30% ethanol, respectively. The ethanol eluate is collected, recovered until there is no alcohol taste, freeze-dried, and crushed into fine powder (particle size not exceeding 200 meshes) to obtain a traditional Chinese medicine extract B with heat-clearing and detoxifying effects.

[0144] Preparation of Chinese herbal medicine extract C:

[0145] Take 10 parts by weight of honeysuckle and 15 parts by weight of isatis root, grind them through a 20-mesh sieve, add 80% ethanol solution, and perform ultrasonic extraction twice:

[0146] The mass of the ethanol solution used in the first ultrasonic extraction was 15 times the mass of the medicinal materials (honeysuckle and isatis root), and the extraction time was 60 min. The mass of the ethanol solution used in the second ultrasonic extraction was 12 times the mass of the medicinal materials (honeysuckle and isatis root), and the extraction time was 60 min.

[0147] Combine the ultrasonic extracts from the two ultrasonic treatments, filter, recover the ethanol, and concentrate until the crude drug concentration in the solution is 0.5 g / mL;

[0148] The AB-8 macroporous resin column was subjected to impurity removal: water and ethanol were used in sequence for impurity removal; the amount of water was 3 times the column volume, the amount of ethanol was 3 times the column volume, and the mass concentration of ethanol was 10%;

[0149] The impurity-removed AB-8 macroporous resin column was then used for elution with 7 column volumes of 50% ethanol, the eluate was collected, the ethanol was recovered, and the extract was concentrated under reduced pressure at 60° C. to an extract with a relative density of 1.18 to obtain Chinese medicine extract C.

[0150] Preparation of Western medicine composition D:

[0151] Take 15 parts by weight of acetaminophen, add an equal amount of ethanol to dissolve it, and then add it dropwise to a 13.5% mass concentration of hydroxypropyl β-cyclodextrin aqueous solution. Stir and mix at 40°C for 5 hours, refrigerate at 8°C for 24 hours, and centrifuge to obtain a precipitate. The precipitate is vacuum-dried at 40°C for 5 hours to obtain an acetaminophen inclusion complex, which is crushed into a fine powder (particle size not exceeding 200 mesh). 5 parts by weight of amantadine hydrochloride and 1 part by weight of artificial bezoar are added and mixed uniformly to obtain a Western medicine composition D with heat-clearing and detoxifying effects.

[0152] Efficacy screening experiment of each extract

[0153] The components of the Chinese and Western medicine combination included Chinese herbal extract A, Chinese herbal extract B, Chinese herbal extract C, and Western medicine composition D. An orthogonal experimental table was designed using the proportions of A, B, C, and D as factors. The components were mixed according to the above ratios to prepare 12 groups of Chinese and Western medicine compositions, namely, Groups I, II, III, IV, V, VI, VII, VIII, IX, X, XI, and XII, as shown in Table 1.

[0154] Table 1 Components and weight percentages of Chinese and Western medicine compositions

[0155]

[0156] Example 1

[0157] The Chinese and Western medicine combination includes:

[0158]

[0159]

[0160] The above components are mixed evenly to obtain a Chinese and Western medicine composition I;

[0161] The Chinese and western medicine composition and corn starch were prepared into 1000 capsules (drug preparation) in a mass ratio of 1:2.5.

[0162] Example 2

[0163] The Chinese and Western medicine combination includes:

[0164]

[0165] The above components are mixed evenly to obtain a Chinese and Western medicine composition II;

[0166] The Chinese and western medicine composition and corn starch were prepared into 1000 capsules (drug preparation) in a mass ratio of 1:1.6.

[0167] Example 3

[0168] The Chinese and Western medicine combination includes:

[0169]

[0170] The above components are mixed evenly to obtain Chinese and Western medicine composition III;

[0171] The Chinese and western medicine composition and corn starch were prepared into 1000 capsules (drug preparation) in a mass ratio of 1:0.9.

[0172] Example 4

[0173] The Chinese and Western medicine combination includes:

[0174]

[0175]

[0176] The above components are mixed evenly to obtain a Chinese and Western medicine composition IV;

[0177] The Chinese and western medicine composition and corn starch were prepared into 1000 capsules (drug preparation) in a mass ratio of 1:1.3.

[0178] Example 5

[0179] The Chinese and Western medicine combination includes:

[0180]

[0181] The above components are mixed evenly to obtain a Chinese and Western medicine composition V;

[0182] The Chinese and western medicine composition and corn starch were prepared into 1000 capsules (drug preparation) in a mass ratio of 1:1.3.

[0183] Example 6

[0184] The Chinese and Western medicine combination includes:

[0185]

[0186] The above components are mixed evenly to obtain a Chinese and Western medicine composition VI;

[0187] The Chinese and western medicine composition and corn starch were prepared into 1000 capsules (drug preparation) in a mass ratio of 1:1.4.

[0188] Example 7

[0189] The Chinese and Western medicine combination includes:

[0190]

[0191]

[0192] The above components are mixed evenly to obtain a Chinese and Western medicine composition VII;

[0193] The Chinese and western medicine composition and corn starch were prepared into 1000 capsules (drug preparation) in a mass ratio of 1:1.1.

[0194] Example 8

[0195] The Chinese and Western medicine combination includes:

[0196]

[0197] The above components are mixed evenly to obtain Chinese and Western medicine composition VIII;

[0198] The Chinese and western medicine composition and corn starch were prepared into 1000 capsules (drug preparation) in a mass ratio of 1:1.2.

[0199] Example 9

[0200] The Chinese and Western medicine combination includes:

[0201]

[0202] The above components are mixed evenly to obtain a Chinese and Western medicine composition IX;

[0203] The Chinese and western medicine composition and corn starch were prepared into 1000 capsules (drug preparation) in a mass ratio of 1:1.2.

[0204] Example 10

[0205] The Chinese and Western medicine combination includes:

[0206] 12 parts by weight of Chinese herbal medicine extract A;

[0207] 9 parts by weight of Chinese herbal medicine extract B;

[0208] 4 parts by weight of Chinese herbal medicine extract C;

[0209] 6 parts by weight of Western medicine composition D;

[0210] The above components are mixed evenly to obtain a Chinese and Western medicine composition X;

[0211] The Chinese and western medicine composition and corn starch were prepared into 1000 capsules (drug preparation) in a mass ratio of 0.7:1.

[0212] Example 11

[0213] The Chinese and Western medicine combination includes:

[0214] 10 parts by weight of Chinese herbal medicine extract A;

[0215] 2 parts by weight of Chinese herbal medicine extract B;

[0216] 12 parts by weight of Chinese herbal medicine extract C;

[0217] 2 parts by weight of Western medicine composition D;

[0218] The above components are mixed evenly to obtain a Chinese and Western medicine composition XⅠ;

[0219] The Chinese and western medicine composition and corn starch were prepared into 1000 capsules (drug preparation) in a mass ratio of 0.9:1.

[0220] Example 12

[0221] The Chinese and Western medicine combination includes:

[0222] 3 parts by weight of Chinese herbal medicine extract A;

[0223] 10 parts by weight of Chinese herbal medicine extract B;

[0224] 3 parts by weight of Chinese herbal medicine extract C;

[0225] Western medicine composition D 7 parts by weight;

[0226] The above components are mixed evenly to obtain a Chinese and Western medicine composition XII;

[0227] The Chinese and western medicine composition and corn starch were prepared into 1000 capsules (drug preparation) in a mass ratio of 1:1.7.

[0228] Comparative Example 1

[0229] The positive western medicine control drug compound acetaminophen capsules were used, with the formula being: acetaminophen 250g, amantadine hydrochloride 100g, caffeine 15g, chlorpheniramine maleate 2g, and artificial bezoar 10g.

[0230] Comparative Example 2

[0231] The positive Chinese medicine control drug Shuanghuanglian Capsule was used, with the formula being: 1875g of honeysuckle, 1875g of scutellaria, and 3750g of forsythia.

[0232] Comparative Example 3

[0233] A Chinese medicine composition control Yaoganyu Capsule was used, with the formula being: 250g of Isatis root, 15g of honeysuckle, 10g of artificial bezoar, 250g of acetaminophen, and 100g of amantadine hydrochloride.

[0234] Comparative Example 4

[0235] The difference from Example 1 is that the Chinese medicine extract B, the Chinese medicine extract C, and the Western medicine composition D are all replaced by the Chinese medicine extract A.

[0236] Comparative Example 5

[0237] The difference from Example 1 is that the Chinese medicine extract A, the Chinese medicine extract C, and the Western medicine composition D are all replaced by the Chinese medicine extract B.

[0238] Comparative Example 6

[0239] The difference from Example 1 is that the Chinese medicine extract A, the Chinese medicine extract B, and the Western medicine composition D are all replaced by the Chinese medicine extract C.

[0240] Comparative Example 7

[0241] The difference from Example 1 is that the Chinese medicine extract A, the Chinese medicine extract B, and the Chinese medicine extract C are all replaced by the Western medicine composition D.

[0242] Comparative Example 8

[0243] The difference from Example 1 is that it does not contain the Chinese medicine extract B and the Chinese medicine extract C, but only contains 8 parts of the Chinese medicine extract A and 5 parts of the Western medicine composition D.

[0244] Comparative Example 9

[0245] The difference from Example 1 is that it does not contain the Chinese medicine extract C, but only contains 6 parts of Chinese medicine extract A, 5 parts of Chinese medicine extract B and 2 parts of Western medicine composition D.

[0246] Anti-inflammatory effect research

[0247] 1.1 Experimental methods

[0248] After one week of adaptive feeding, 18-22 g male mice (sourced from Changchun Yisi Experimental Animal Technology Co., Ltd.) were randomly divided into 23 groups (n=6) each: a blank group, a model group, a comparative example 1 compound paracetamol and amantadine capsule group (0.1 g / kg), a comparative example 3 Ganyu capsule group (0.1 g / kg), a comparative example 2 Shuanghuanglian capsule group (0.6 g / kg), comparative example Chinese and Western medicine combination groups 4-9 (0.1 g / kg), and Chinese and Western medicine combination groups I-XII (0.1 g / kg). The test drugs were suspended in 0.5% CMC-Na and administered orally at a rate of 0.1 mL / 10 g once daily for 7 consecutive days. The normal control group and the model group were given an equal amount of CMC-Na by oral gavage. Before the experiment, the mice were fasted but not watered for 12 h. One hour after the last administration, 20 μL of xylene was evenly applied to the right ear (both sides) using a pipette. 0.5 h later, the mice were killed by cervical dislocation. The left and right ear shells were cut off, and ear pieces with a diameter of 8 mm were taken from the same part of the left and right ears using an electric ear swelling punch. The weight was measured, and the differences between the groups were observed. The swelling degree and swelling inhibition rate were calculated according to formulas (1) to (2). The results are shown in Table 2.

[0249] Swelling degree (mg) = right ear piece mass - left ear piece mass (Formula (1));

[0250] Swelling inhibition rate (%) = (swelling degree of model group - swelling degree of drug-treated group) / swelling degree of model group × 100%

[0251] Formula (2).

[0252] 1.2 Effect on mouse ear swelling

[0253] Table 2 Effects on ear swelling in mice ( n=6)

[0254]

[0255]

[0256] Note: Compared with the blank group, △Δ△ P<0.001; compared with the model group, * P<0.05, *** P<0.001; compared with Ganyu capsule group, ## P<0.01.

[0257] As shown in Table 2, compared with the blank group, the ear swelling of the mice in the model group was significantly increased (P < 0.001), indicating that the model was successfully established. Compared with the model group, the ear swelling of the mice in all the drug-treated groups was significantly reduced (P < 0.001). Compared with the Yuanganyu Capsule group, the ear swelling of the mice in the Chinese and Western medicine combination group VI was significantly reduced (P < 0.01), with a swelling inhibition rate of 35.90%, which was superior to that of the other combination groups.

[0258] Expectorant Effect Research

[0259] 2.1 Experimental methods

[0260] Male mice weighing 18-22 g (sourced from Changchun Yisi Experimental Animal Technology Co., Ltd.) were acclimated for one week and randomly divided into 22 groups: a blank group, a compound paracetamol and amantadine capsule group (0.1 g / kg), a Yuanganyu capsule group (0.1 g / kg), a Shuanghuanglian capsule group (0.6 g / kg), a comparative Chinese and Western medicine combination group 4-9 (0.1 g / kg), and Chinese and Western medicine combination groups I-XII (0.1 g / kg). Each group consisted of six mice, half male and half female. The test drugs were suspended in 0.5% CMC-Na by oral gavage at 0.1 mL / 10 g once daily for 7 consecutive days. The normal control group received an equal amount of CMC-Na by oral gavage. Thirty minutes after the last dose, 0.1 mL / 10 g of a 0.5% phenol red solution was injected intraperitoneally. Thirty minutes later, the animals were sacrificed and fixed in the dorsal position. The skin was incised along the midline of the neck, and the surrounding tissue was stripped to expose the trachea. The trachea was ligated beneath the thyroid cartilage and at the tracheal bifurcation. The trachea was excised and placed in an EP tube containing 2 mL of 5% sodium bicarbonate solution. The tube was allowed to rest for 30 minutes. The OD value at a wavelength of 546 nm was measured using a microplate reader. A phenol red standard curve was constructed, and tracheal phenol red excretion was calculated based on the standard curve. The results are shown in Table 3.

[0261] 2.2 Effects on phenol red secretion in mouse trachea

[0262] Table 3 Effects on tracheal phenol red secretion ( n=6)

[0263]

[0264]

[0265] Note: Compared with the blank group, *** P < 0.001, ** P < 0.01, * P<0.05; compared with Ganyu capsule group, ## P < 0.01, # P<0.05.

[0266] As can be seen from Table 3, compared with the blank group, each drug-treated group can significantly increase the tracheal phenol red excretion of mice (P < 0.001). Compared with the Yuanganyu capsule group, the tracheal phenol red excretion of the Chinese and Western medicine combination groups II and VI was significantly reduced (P < 0.01, P < 0.05), and the Chinese medicine combination VI was superior to the other combination groups.

[0267] Antitussive effect research

[0268] 3.1 Experimental methods

[0269] Male mice weighing 18-22 g (from Changchun Yisi Experimental Animal Technology Co., Ltd.) were acclimated for one week and fasted for 12 hours before the experiment. They were placed in a 5000 mL homemade glass apparatus and sprayed with 25% ammonia water at a constant pressure for 30 seconds using a nebulizer. The mice were observed for cough reflex (strong abdominal muscle contraction with simultaneous exhalation through the mouth). Cough reflexes of ≥3 times within 1 minute were considered qualified for the initial cough induction screening. 132 mice that passed the initial screening were randomly divided into 22 groups based on body weight: the model group, the compound acetaminophen capsule group (0.1 g / kg), the Yuanganyu capsule group (0.1 g / kg), the Shuanghuanglian capsule group (0.6 g / kg), the comparative Chinese medicine composition groups 4-9 (0.1 g / kg), and the Chinese medicine composition groups I-XII (0.1 g / kg), with 6 mice in each group, half male and half female. All test drugs were suspended in 0.5% CMC-Na and administered orally at a rate of 0.1 mL / 10 g once daily for 7 consecutive days. Model group mice were given an equal amount of CMC-Na by oral gavage. One hour after the last dose, the mice were placed in the above-mentioned apparatus and time was recorded with a stopwatch. The cough latency (the time from the start of spraying to the first cough) and the number of coughs within 3 minutes were observed. The cough suppression rate was calculated according to formula (3). The results are shown in Figure 4.

[0270] Cough suppression rate (%) = (number of coughs in model group mice - number of coughs in drug-treated group mice) / number of coughs in model group mice × 100% Formula (3).

[0271] 3.2 Effects on coughing in mice

[0272] Table 4 Effects on cough in mice ( n=6)

[0273]

[0274] Note: Compared with the model group, ***P<0.001, **P<0.01, ***P<0.001; compared with the Ganyu capsule group, #P<0.05.

[0275] As can be seen from Table 4, compared with the model group, the cough latency of mice in each drug-treated group was significantly prolonged (P < 0.01, P < 0.05), and the number of coughs was reduced (P < 0.001, P < 0.01, P < 0.05). Compared with the Yuanganyu capsule group, the cough latency of mice in the Chinese medicine composition VI group was significantly prolonged (P < 0.05), and the number of coughs was significantly reduced (P < 0.05). The cough suppression rate reached 23.05%, which was better than that of the other combination groups.

[0276] In summary, the Chinese and Western medicine composition VI of the present invention can effectively reduce ear swelling in mice and inhibit inflammatory response; it can increase the secretion of phenol red in the mouse trachea and has a significant expectorant effect; at the same time, it can effectively reduce the number of times mice cough when stimulated by ammonia, indicating that it has a certain antitussive effect and is better than other Chinese and Western medicine composition groups.

[0277] The above embodiments are intended only to facilitate understanding of the methods and core concepts of the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention is not limited to the embodiments shown herein, but is intended to be construed in the widest manner consistent with the principles and novel features disclosed herein.

Claims

1. A Chinese and Western medicine composition for treating wind-heat cold, comprising, by weight: The Chinese medicine extract A is prepared by CO2 supercritical extraction and volatile oil inclusion of honeysuckle; The Chinese medicine extract B is obtained by enzymatic hydrolysis of honeysuckle and isatis root; The Chinese medicine extract C is prepared by ultrasonic extraction of honeysuckle and isatis root; The western medicine composition D is prepared from raw material components including artificial bezoar, acetaminophen and amantadine hydrochloride.

2. The Chinese and Western medicine composition according to claim 1, characterized in that The Chinese and Western medicine composition comprises, by weight:

3. The Chinese and Western medicine composition according to claim 1, characterized in that The preparation method of the Chinese medicine extract A comprises the following steps: a1) crushing the honeysuckle and performing CO2 supercritical extraction; a2) separating the components after the CO2 supercritical extraction to obtain volatile oil; a3) dissolving the volatile oil in ethanol and adding the solution dropwise to a β-cyclodextrin aqueous solution for volatile oil inclusion to obtain a volatile oil inclusion complex, namely, the Chinese herbal extract A.

4. The Chinese and Western medicine composition according to claim 1, characterized in that The preparation method of the Chinese medicine extract B comprises the following steps: b1) crushing honeysuckle and slicing isatis root, decocting with water under the action of a complex enzyme, and reflux extraction to obtain an extract; the complex enzyme used in the enzymatic hydrolysis is cellulase and pectinase; the mass ratio is 0.5-1.5:1-2; b2) filtering the extract, concentrating the obtained filtrate into a clear paste, adding ethanol, allowing the mixture to settle, and filtering to obtain a supernatant and a precipitate; b3) mixing the precipitate with aqueous hydrochloric acid solution, adjusting the pH value to 6-7, dissolving with ethanol, filtering, combining the obtained filtrate with the supernatant, concentrating, and purifying with an LS-303 macroporous resin column to obtain a Chinese herbal extract B.

5. The Chinese and Western medicine composition according to claim 1, characterized in that: The preparation method of the Chinese medicine extract C comprises the following steps: c1) crushing the honeysuckle and isatis root, and ultrasonically extracting them with an ethanol solution to obtain an ultrasonic extract; c2) filtering, recovering ethanol, and concentrating the liquid medicine; c3) purifying the medicinal solution using an AB-8 macroporous resin column to obtain a Chinese herbal medicine extract C.

6. The Chinese and Western medicine composition according to claim 1, characterized in that: The mass ratio of the artificial bezoar, acetaminophen and amantadine hydrochloride is 0.5-1.5:13-17:3-7.

7. The Chinese and Western medicine composition according to claim 1, characterized in that: The preparation method of the western medicine composition D comprises the following steps: d1) dissolving acetaminophen in ethanol and adding the solution dropwise to the hydroxypropyl β-cyclodextrin aqueous solution, stirring and mixing, refrigerating, centrifuging, and vacuum drying the resulting precipitate to obtain an acetaminophen inclusion complex; d2) Grinding the acetaminophen inclusion compound into fine powder, and mixing it with amantadine hydrochloride and artificial bezoar to obtain a western medicine composition D.

8. The method for preparing the Chinese and Western medicine composition according to any one of claims 1 to 7, comprising the following steps: The Chinese medicine extract A, the Chinese medicine extract B, the Chinese medicine extract C and the western medicine composition D are mixed to obtain a Chinese and western medicine composition.

9. Use of the Chinese and Western medicine combination according to any one of claims 1 to 7 in the preparation of a medicine for preventing or treating wind-heat colds.

10. Use of the Chinese and Western medicine combination according to any one of claims 1 to 7 in the preparation of anti-inflammatory drugs.

11. Use of the Chinese and Western medicine combination according to any one of claims 1 to 7 in the preparation of antitussive drugs.

12. A pharmaceutical preparation, comprising the Chinese and Western medicine combination according to any one of claims 1 to 7 and pharmaceutically acceptable excipients.

13. The pharmaceutical preparation according to claim 12, characterized in that The dosage form of the pharmaceutical preparation is a mixture, syrup, tablet, granule or capsule.

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