A compound Chuanbei cough-relieving composition, syrup and preparation method thereof

Abstract

The present invention relates to a compound Chuanbei antitussive composition, syrup, and preparation method thereof, belonging to the technical field of traditional Chinese medicine. The compound Chuanbei antitussive composition is made from traditional Chinese medicine fermented granules, prepared rehmannia root, raw rehmannia root, Radix Angelicae Sinensis root, white peony root, fritillaria cirrhosa, ophiopogon japonicus, and lily. The traditional Chinese medicine fermented granules are made from licorice root, platycodon grandiflorum, and Scrophularia ningpoensis. The raw materials are first enzymatically hydrolyzed with cellulase to obtain an enzymatic hydrolyzate. The enzymatic hydrolyzate is then mixed and fermented with Lactobacillus plantarum, Candida utilis, and Eurotium cristatum to obtain a fermentation liquid. The mixed fermentation liquid is then sterilized, filtered, concentrated, and granulated to obtain the traditional Chinese medicine fermented granules. The resulting compound Chuanbei antitussive composition has good yin-nourishing and lung-moistening, cough-relieving and asthma-relieving effects.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and in particular to a compound Fritillaria cirrhosa cough-relieving composition, a syrup and a preparation method thereof. Background Art

[0002] Baihe Gujin Tang, a recipe containing cooked rehmannia root, raw rehmannia root, Radix Angelicae Sinensis root, white peony root, licorice root, platycodon grandiflorum, Scrophularia ningpoensis root, Fritillaria thunbergii root, Ophiopogon japonicus root, and lily bulb, is primarily used to treat lung and kidney yin deficiency and asthenic fire. Symptoms include cough, wheezing, blood in sputum, dry and sore throat, dizziness, afternoon hot flashes, a red tongue with little coating, and a thready pulse. It is commonly used clinically to treat lung and kidney yin deficiency and asthenic fire, such as pulmonary tuberculosis, chronic bronchitis, hemoptysis due to bronchiectasis, chronic pharyngitis, and spontaneous pneumothorax.

[0003] Traditional Chinese medicine decoction methods do have some inconveniences and limitations. For example, different herbs and prescriptions require different decoction times, which must be strictly followed according to the doctor's instructions, otherwise the efficacy may be affected. The heat must be adjusted according to the nature of the medicine, typically using high heat before boiling and then simmering to maintain a slight simmer. This can be difficult for non-professionals to master. While herbs can typically be decocted two or three times to maximize their effectiveness, this requires multiple steps, which is tedious and prevents timely administration upon the onset of symptoms. Summary of the Invention

[0004] The purpose of the present invention is to overcome the shortcomings of the existing technology and provide a compound Chuanbei cough-relieving composition, syrup and preparation method thereof, and use multi-strain mixed fermentation to improve the process of the existing Chinese medicine formula to promote the improvement of the composition's efficacy in nourishing yin and moistening the lungs, resolving phlegm and relieving cough.

[0005] To achieve the above object, the technical solution adopted by the present invention is:

[0006] In a first aspect, the present invention provides a compound Chuanbei cough-relieving composition, which is prepared from the following raw materials in parts by weight: 10-15 parts of a traditional Chinese medicine fermentation composition, 7-10 parts of cooked rehmannia, 7-10 parts of raw rehmannia, 7-10 parts of Radix Angelicae Sinensis, 1-4 parts of white peony root, 10-15 parts of Fritillariae Cirrhosae, 10-15 parts of Radix Ophiopogonis, and 10-15 parts of lily; wherein the traditional Chinese medicine fermentation composition includes the following raw materials in parts by weight: 1-4 parts of Scrophulariae, 1-4 parts of Platycodon grandiflorum, and 1-4 parts of Licorice;

[0007] The preparation method of the traditional Chinese medicine fermentation composition comprises the following steps:

[0008] S1. Grind licorice, platycodon grandiflorum and Scrophularia ningpoensis to obtain a mixed powder;

[0009] S2. Add 5-7 times the mass of deionized water to the mixed powder and stir evenly to obtain a mixed solution;

[0010] S3, adding cellulase to the mixed solution for enzymolysis, wherein the amount of cellulase added is 5-7 wt% of the mixed solution, the enzymolysis temperature is 30-35 ° C, and the enzymolysis time is 3-6 h. After the enzymolysis is completed, filtering is performed to obtain an enzymolysis solution;

[0011] S4. Adding glucose and peptone to the enzymatic hydrolysate, mixing well, sterilizing and filtering the enzymatic hydrolysate to obtain a filtrate;

[0012] S5. Inoculate mixed bacteria into the filtrate for mixed fermentation, sterilize at high temperature and filter after the fermentation is completed to obtain a Chinese medicine fermentation liquid, concentrate the Chinese medicine fermentation liquid, spray-dry and granulate it to obtain a granular Chinese medicine fermentation composition; wherein the mixed bacteria is a composition of Lactobacillus plantarum, Candida utilis, and Eurotium cristatum in a mass ratio of 1:1:(2-4), the total amount of bacteria added is 5-7wt% of the filtrate, the fermentation time is 12-16h, the fermentation temperature is 28-30°C, and the fermentation pH is 5.8-7.1.

[0013] This prescription is based on lung and kidney yin deficiency. The lungs are the mother of the kidneys, and lung deficiency affects the kidneys. Prolonged illness leads to lung and kidney yin deficiency, which generates internal heat. Deficiency of yin generates upward inflammation of the deficiency fire, which prevents the lungs from descending and causing cough and asthma. The deficiency fire burns body fluids, leading to dry and sore throats, afternoon hot flashes, and even burns the lung meridians, resulting in blood in sputum. Treatment should nourish the yin and blood of the lungs and kidneys while also clearing heat, resolving phlegm, and relieving coughs, taking both the diagram and the original into account. Lily bulbs are sweet, bitter, and slightly cold in this prescription, nourishing yin, clearing heat, moistening the lungs, and relieving coughs. Both raw and cooked rehmannia nourish the kidneys and strengthen water, with the raw rehmannia also cooling blood and stopping bleeding. These three herbs together constitute a common combination for nourishing the lungs and kidneys, tonifying both metal and water, and serve as the main herb. Ophiopogon japonicus is sweet and cold, complementing lily bulbs to nourish yin, clear heat, and moisten the lungs to relieve coughs. Scrophularia ningpoensis, salty and cold, aids the two rehmannia roots in nourishing yin and strengthening water, clearing deficiency fire, and also benefiting the throat. These three herbs serve as the auxiliary herb. Angelica sinensis treats cough and shortness of breath, and is combined with white peony root to nourish and regulate blood. Fritillaria thunbergii clears heat and moistens the lungs, resolves phlegm and relieves cough, both serving as adjuvants. Platycodon grandiflorum clears the lungs and relieves sore throat, resolves phlegm and disperses stagnation, and also carries the herbs upward. Raw licorice clears heat and purges fire, harmonizing the other herbs, serving as adjuvants.

[0014] The present invention selects liquorice, platycodon and figwort as raw materials, first uses cellulase to enzymolyze them to obtain an enzymolyzate, then uses Lactobacillus plantarum, Candida utilis and Eurotium cristatum to mix and ferment the enzymolyzate to obtain a fermentation liquid, and then sterilizes, filters, concentrates and granulates the mixed fermentation liquid to obtain traditional Chinese medicine fermentation granules, wherein Eurotium cristatum can convert and decompose phenolic substances in liquorice, platycodon and figwort to produce flavonoid components, and the flavonoid components have good antioxidant properties, which are helpful to protect the respiratory mucosa and reduce oxidative stress. The inflammatory response caused by the flu has a certain auxiliary effect on cough relief. Furthermore, the secondary metabolites of Eurotium cristatum have certain antibacterial activity, which can inhibit or kill bacteria that cause respiratory infections, reducing coughs and other symptoms. The secondary metabolites of Lactobacillus plantarum can improve the biological barrier and enhance immunity. The mannose and β-glucan contained in Candida utilis act as immunostimulants, stimulating or enhancing the body's immune function. Candida utilis and its secondary metabolites have a positive effect on cough relief and reducing inflammatory responses. Mixed fermentation of these three strains can share metabolites, thus achieving nutritional complementarity. Furthermore, Lactobacillus plantarum has a strong ability to decompose proteins and can produce a variety of amino acids, providing nutrients for Candida utilis. Candida utilis metabolites, such as pyruvate, can promote the growth of Lactobacillus plantarum.

[0015] Preferably, in step S5 of the method for preparing the traditional Chinese medicine fermentation composition, the mass ratio of Lactobacillus plantarum, Candida utilis, and Eurotium cristatum is 1:1:(3-4).

[0016] Preferably, in step S1, the liquorice, platycodon and figwort are ground to 400-600 mesh.

[0017] Preferably, in step S4, the amount of glucose added is 9-12 wt% of the enzymatic hydrolysate, and the amount of peptone added is 3 wt% of the enzymatic hydrolysate.

[0018] In a second aspect, the present invention provides a method for preparing a composite Fritillaria cirrhosa cough suppressant composition, comprising the following steps:

[0019] (1) Radix Angelicae Sinensis, Radix Paeoniae Alba, Lilium Bulb, Radix Ophiopogonis, and Fritillariae Cirrhosae Bulb are mixed, and then 8-12 times the volume of 65-75% ethanol solution is added and soaked for 12-48 hours, followed by reflux extraction 2-3 times, each time for 1-3 hours, and the extracts are combined;

[0020] (2) Mix the cooked and raw rehmannia roots, add 8-12 times the amount of water, and boil for 2-3 times, each time for 1-3 hours. Combine the decoctions.

[0021] (3) The extract solution and the decoction solution are combined to obtain an extract solution, and the Chinese medicine fermentation composition is added thereto, stirred evenly, and concentrated to 0.5-1 times the amount of the corresponding raw medicine to obtain the compound Fritillaria cirrhosa cough suppressant composition.

[0022] In a third aspect, the present invention provides a compound Fritillaria cirrhosa cough syrup comprising the aforementioned compound Fritillaria cirrhosa cough syrup, sucrose and excipients; the mass ratio of the compound Fritillaria cirrhosa cough syrup, sucrose and excipients is (10-15): (80-90):1.

[0023] Preferably, the auxiliary material is a preservative.

[0024] More preferably, the preservative is at least one of potassium sorbate, sodium benzoate and ethylparaben.

[0025] In a fourth aspect, the present invention provides a method for preparing the compound Chuanbei cough syrup, comprising the following steps:

[0026] The compound Chuanbei cough relieving composition, sucrose, auxiliary materials and water are heated and stirred evenly, and then cooled to room temperature to obtain the compound Chuanbei cough relieving syrup.

[0027] Preferably, the heating and stirring is carried out at a temperature of 70-80° C., for 5-10 minutes, and at a stirring speed of 200-300 rpm.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] The compound Chuanbei composition of the present invention is made of traditional Chinese medicine fermented granules, prepared rehmannia, raw rehmannia, Radix Angelicae Sinensis, white peony root, Fritillaria cirrhosa, Radix Ophiopogonis, and lily. The traditional Chinese medicine fermented granules are made from licorice, platycodon, and Scrophularia ningpoensis. The raw materials are first enzymatically hydrolyzed with cellulase to obtain an enzymatic hydrolyzate, and then the enzymatic hydrolyzate is mixed and fermented with Lactobacillus plantarum, Candida utilis, and Eurotium coronatum to obtain a fermentation liquid. The mixed fermentation liquid is then sterilized, filtered, concentrated, and granulated to obtain the traditional Chinese medicine fermented granules. Studies have found that the fermentation product obtained by mixed fermentation of licorice, platycodon, and Scrophularia ningpoensis with Lactobacillus plantarum, Candida utilis, and Eurotium coronatum with prepared rehmannia, raw rehmannia, Radix Angelicae Sinensis, white peony root, Fritillaria cirrhosa, Radix Ophiopogonis, and lily has a better cough and asthma relief effect than simply compounding all the ingredients. DETAILED DESCRIPTION

[0030] In order to better understand the present invention, the present invention is further described below in conjunction with specific application examples, wherein the terms used in the application examples are for describing specific embodiments and do not constitute a limitation on the scope of protection of the present invention.

[0031] In the following examples, the experimental methods without specific conditions are generally based on conventional conditions or the conditions recommended by the manufacturer. Unless otherwise specified, the percentages and parts by mass are calculated.

[0032] Some of the raw materials and their sources are as follows:

[0033] Rehmannia glutinosa: purchased from Bozhou Ruantang Pharmaceutical Co., Ltd.

[0034] Radix Rehmanniae: purchased from Bozhou Ruantang Pharmaceutical Co., Ltd.

[0035] Radix Angelicae Sinensis: purchased from Bozhou Ruantang Pharmaceutical Co., Ltd.

[0036] White peony root: purchased from Bozhou Ruantang Pharmaceutical Co., Ltd.

[0037] Fritillaria cirrhosa: purchased from Bozhou Ruantang Pharmaceutical Co., Ltd.

[0038] Ophiopogon japonicus: purchased from Bozhou Ruantang Pharmaceutical Co., Ltd.

[0039] Lily: purchased from Bozhou Ruantang Pharmaceutical Co., Ltd.

[0040] Licorice: purchased from Bozhou Ruantang Pharmaceutical Co., Ltd.

[0041] Platycodon grandiflorum: purchased from Bozhou Ruantang Pharmaceutical Co., Ltd.

[0042] Scrophulariaceae: purchased from Bozhou Ruantang Pharmaceutical Co., Ltd.

[0043] Cellulase: purchased from Xiasheng Group, Xiasheng cellulase (CEL-01 model), product number: FDY-2243, enzyme activity: 11000u / mL;

[0044] Lactobacillus plantarum: purchased from Ningbo Mingzhou Biotechnology Co., Ltd., number BMZ239542;

[0045] Candida utilis: purchased from Ningbo Mingzhou Biotechnology Co., Ltd., number B98236;

[0046] Eurotium cristatum was purchased from Ningbo Mingzhou Biotechnology Co., Ltd. with the number BMZ142110.

[0047] Example 1

[0048] A compound Chuanbei cough-relieving composition, comprising the following raw materials in parts by weight: 12 parts of a traditional Chinese medicine fermentation composition, 9 parts of cooked rehmannia root, 9 parts of raw rehmannia root, 12 parts of Radix Angelicae Sinensis, 3 parts of white peony root, 12 parts of Fritillaria cirrhosa, 12 parts of Radix Ophiopogonis, and 12 parts of lily; wherein the traditional Chinese medicine fermentation composition comprises the following raw materials in parts by weight: 3 parts of Scrophularia ningpoensis, 2 parts of Platycodon grandiflorum, and 3 parts of Licorice root;

[0049] The preparation method of the traditional Chinese medicine fermentation composition comprises the following steps:

[0050] S1. Grind licorice, platycodon grandiflorum and Scrophularia ningpoensis to 500 mesh to obtain a mixed powder;

[0051] S2. Add deionized water 6 times the mass of the mixed powder to the mixed powder and stir evenly to obtain a mixed solution;

[0052] S3, adding cellulase to the mixed solution for enzymolysis, wherein the amount of cellulase added is 6 wt% of the mixed solution, the enzymolysis temperature is 32° C., the enzymolysis time is 5 h, and after the enzymolysis is completed, filtering is performed to obtain an enzymolysis solution;

[0053] S4. Add 10 wt% glucose and 3 wt% peptone to the enzymatic hydrolyzate, mix well, sterilize at 105° C. for 40 min, and filter to obtain a filtrate;

[0054] S5. Inoculate mixed bacteria into the filtrate for mixed fermentation. After the fermentation is completed, sterilize at high temperature and filter to obtain a traditional Chinese medicine fermentation liquid, wherein the mixed bacteria is a composition of Lactobacillus plantarum, Candida utilis, and Eurotium cristatum in a mass ratio of 1:1:3, the total amount of bacteria added is 6wt% of the filtrate, the fermentation time is 14h, the fermentation temperature is 28°C, and the fermentation pH is 6.0.

[0055] The preparation method of the compound Chuanbei cough-relieving composition comprises the following steps:

[0056] (1) Radix Angelicae Sinensis, Radix Paeoniae Alba, Lilium Bulb, Radix Ophiopogonis, and Fritillariae Cirrhosae were mixed, and then 10 times the volume of 70% ethanol solution was added and soaked for 36 hours. The mixture was then refluxed and extracted twice, each time for 2 hours, and the extracts were combined;

[0057] (2) Mix cooked and raw rehmannia, add 10 times the amount of water, and boil twice, each time for 2 hours, and combine the decoctions;

[0058] (3) The extract and the decoction are combined to obtain an extract solution, and the Chinese medicine fermentation composition is added thereto, stirred evenly, and concentrated to 0.6 times the amount of the corresponding raw medicine to obtain the compound Fritillaria cirrhosa cough-relieving composition.

[0059] Example 2

[0060] A compound Fritillaria cirrhosa cough-relieving composition, comprising the following raw materials in parts by weight: 10 parts of a traditional Chinese medicine fermentation composition, 7 parts of cooked rehmannia root, 7 parts of raw rehmannia root, 7 parts of Radix Angelicae Sinensis root, 1 part of white peony root, 10 parts of Fritillaria thunbergii, 10 parts of Radix Ophiopogonis japonicus, and 10 parts of lily bulbs; wherein the traditional Chinese medicine fermentation composition comprises the following raw materials in parts by weight: 1 part of Scrophularia ningpoensis root, 1 part of Platycodon grandiflorum, and 4 parts of Glycyrrhiza uralensis root;

[0061] The preparation method of the traditional Chinese medicine fermentation composition comprises the following steps:

[0062] S1. Grind licorice, platycodon grandiflorum and Scrophularia ningpoensis to 400 mesh to obtain a mixed powder;

[0063] S2. Add deionized water 5 times the mass of the mixed powder to the mixed powder and stir evenly to obtain a mixed solution;

[0064] S3, adding cellulase to the mixed solution for enzymolysis, wherein the amount of cellulase added is 5 wt% of the mixed solution, the enzymolysis temperature is 30° C., the enzymolysis time is 3 h, and after the enzymolysis is completed, filtering is performed to obtain an enzymolysis solution;

[0065] S4, adding 9 wt% glucose and 3 wt% peptone to the enzymatic hydrolyzate, mixing well, sterilizing at 105°C for 30 min, and filtering to obtain a filtrate;

[0066] S5. Inoculate mixed bacteria into the filtrate for mixed fermentation. After the fermentation is completed, sterilize at high temperature and filter to obtain a traditional Chinese medicine fermentation liquid, wherein the mixed bacteria is a composition of Lactobacillus plantarum, Candida utilis, and Eurotium cristatum in a mass ratio of 1:1:2, the total amount of bacteria added is 5wt% of the filtrate, the fermentation time is 12h, the fermentation temperature is 28°C, and the fermentation pH is 5.8.

[0067] The preparation method of the compound Chuanbei cough-relieving composition comprises the following steps:

[0068] (1) Radix Angelicae Sinensis, Radix Paeoniae Alba, Lilium Bulb, Radix Ophiopogonis, and Fritillariae Cirrhosae were mixed, and then 8 times the volume of 65% ethanol solution was added and soaked for 12 hours. The mixture was then refluxed and extracted twice, each time for 1 hour, and the extracts were combined;

[0069] (2) Mix cooked and raw rehmannia, add 8 times the amount of water, and boil twice, each time for 1 hour, and combine the decoctions;

[0070] (3) The extract and the decoction are combined to obtain an extract solution, and the Chinese medicine fermentation composition is added thereto, stirred evenly, and concentrated to 0.5 times the amount of the corresponding raw medicine to obtain the compound Fritillaria cirrhosa cough-relieving composition.

[0071] Example 3

[0072] A compound Chuanbei cough-relieving composition, prepared from the following raw materials in parts by weight: 15 parts of a traditional Chinese medicine fermentation composition, 10 parts of cooked rehmannia root, 10 parts of raw rehmannia root, 10 parts of Radix Angelicae Sinensis, 4 parts of white peony root, 15 parts of Fritillaria thunbergii, 15 parts of Radix Ophiopogonis, and 15 parts of lily; wherein the traditional Chinese medicine fermentation composition includes the following raw materials in parts by weight: 4 parts of Scrophularia ningpoensis, 4 parts of Platycodon grandiflorum, and 1 part of Licorice root;

[0073] The preparation method of the traditional Chinese medicine fermentation composition comprises the following steps:

[0074] S1. Grind licorice, platycodon grandiflorum and Scrophularia ningpoensis to 600 mesh to obtain a mixed powder;

[0075] S2. Add deionized water 7 times the mass of the mixed powder to the mixed powder and stir evenly to obtain a mixed solution;

[0076] S3, adding cellulase to the mixed solution for enzymolysis, wherein the amount of cellulase added is 7 wt% of the mixed solution, the enzymolysis temperature is 35° C., the enzymolysis time is 6 h, and after the enzymolysis is completed, filtering is performed to obtain an enzymolysis solution;

[0077] S4. Add 12 wt% glucose and 3 wt% peptone to the enzymatic hydrolyzate, mix well, sterilize at 105° C. for 30 min, and filter to obtain a filtrate;

[0078] S5. Inoculate mixed bacteria into the filtrate for mixed fermentation. After the fermentation is completed, sterilize at high temperature and filter to obtain a traditional Chinese medicine fermentation liquid, wherein the mixed bacteria is a composition of Lactobacillus plantarum, Candida utilis, and Eurotium cristatum in a mass ratio of 1:1:4, the total amount of bacteria added is 7wt% of the filtrate, the fermentation time is 16h, the fermentation temperature is 30°C, and the fermentation pH is 7.1.

[0079] The preparation method of the compound Chuanbei cough-relieving composition comprises the following steps:

[0080] (1) Radix Angelicae Sinensis, Radix Paeoniae Alba, Lilium Bulb, Radix Ophiopogonis, and Fritillariae Cirrhosae were mixed, and then added with 12 times the volume of 75% ethanol solution and soaked for 48 hours. The mixture was then refluxed and extracted three times for 3 hours each time, and the extracts were combined.

[0081] (2) Mix cooked and raw rehmannia, add 12 times the amount of water, and boil three times for 3 hours each time. Combine the decoctions.

[0082] (3) The extract and the decoction are combined to obtain an extract solution, and the Chinese medicine fermentation composition is added thereto, stirred evenly, and concentrated to 1 times the amount of the corresponding raw medicine to obtain the compound Fritillaria cirrhosa cough-relieving composition.

[0083] Comparative Example 1

[0084] The difference between Comparative Example 1 and Example 1 is that Scrophularia, Platycodon and Glycyrrhiza are not subjected to steps S1 to S5, that is, they are not subjected to enzymatic hydrolysis and fermentation treatments, and Platycodon is subjected to alcohol extraction together with other alcohol-extracted components in step (1) of the preparation method of the compound Fritillaria cirrhosa cough-relieving composition; Scrophularia and Glycyrrhiza are subjected to water extraction together with other water-extracted components in step (2) of the preparation method of the compound Fritillaria cirrhosa cough-relieving composition.

[0085] Comparative Example 2

[0086] The difference between Comparative Example 2 and Example 1 is that the Chinese medicinal fermentation composition does not include the enzymatic hydrolysis step S3.

[0087] Comparative Example 3

[0088] The difference between Comparative Example 3 and Example 1 is that the Chinese medicinal fermentation composition does not include the mixed bacteria fermentation step S4-S5.

[0089] Comparative Example 4

[0090] The difference between Comparative Example 4 and Example 1 is that the total amount of the mixed bacteria remains unchanged, Lactobacillus plantarum is not added, and the missing amount is supplemented by Candida utilis and Eurotium cristatum in a mass ratio of 1:3.

[0091] Comparative Example 5

[0092] The difference between Comparative Example 5 and Example 1 is that the total amount of mixed bacteria remains unchanged, Candida utilis is not added, and the missing amount is supplemented by Lactobacillus plantarum and Eurotium cristatum in a mass ratio of 1:3.

[0093] Comparative Example 6

[0094] The difference between Comparative Example 6 and Example 1 is that the total amount of mixed bacteria remains unchanged, Eurotium cristatum is not added, and the missing amount is supplemented by Lactobacillus plantarum and Candida utilis in a mass ratio of 1:1.

[0095] Comparative Example 7

[0096] The difference between Comparative Example 7 and Example 1 is that the total amount of fermentation bacteria remains unchanged, and the mass ratio of Lactobacillus plantarum, Candida utilis, and Eurotium cristatum is 3:1:1.

[0097] Comparative Example 8

[0098] The difference between Comparative Example 8 and Example 1 is that the total amount of fermentation bacteria remains unchanged, and the mass ratio of Lactobacillus plantarum, Candida utilis, and Eurotium cristatum is 1:3:1.

[0099] Comparative Example 9

[0100] The difference between Comparative Example 9 and Example 1 is that the total amount of fermentation bacteria remains unchanged, and the mass ratio of Lactobacillus plantarum, Candida utilis, and Eurotium cristatum is 1:1:1.

[0101] Application Examples 1-3 and Comparative Application Examples 1-9

[0102] The compound Chuanbei cough relieving compositions of Examples 1-3 and Comparative Examples 1-9 were respectively prepared into compound Chuanbei cough relieving syrups, which specifically comprised the following raw materials in parts by weight:

[0103] 12 parts of compound Fritillaria cirrhosa cough suppressant composition, 85 parts of sucrose, and 1 part of a preservative, wherein the preservative is potassium sorbate.

[0104] The preparation method of the compound Chuanbei cough syrup comprises the following steps:

[0105] The compound Fritillaria cirrhosa cough syrup, sucrose, a preservative and 500 mL of water were heated and stirred at 75° C. and 250 rpm for 8 minutes, and then cooled to room temperature to obtain the compound Fritillaria cirrhosa cough syrup.

[0106] Test 1: Cough Suppression Test

[0107] Test materials: Ammonia water (Guangdong Chemical Reagent Engineering Research and Development Center), codeine phosphate (Qinghai Pharmaceutical Co., Ltd.).

[0108] Experimental animals: KM mice (half male and half female), weighing 24±4 g, SPF grade; purchased from Guangdong Weitonglihua Experimental Animal Technology Co., Ltd.

[0109] Test instrument: ultrasonic atomizer (purchased from Yuehua WH-2000).

[0110] Experimental methods:

[0111] (1) Animal screening

[0112] After the thermal ultrasonic atomizer, add the 40mL ammonia solution (12.5wt%) of fresh preparation. It is 1000mL that mice are put into the beaker of volume, the beaker mouth is airtight with preservative film, and opens two mouths (one for inserting ultrasonic atomizer outlet pipe, the other is ventilation hole). After ultrasonic atomizer is continuously passed into ammonia for 60s with minimum spray intensity, immediately close and open preservative film rapidly so that ammonia is naturally diffused. When passing into ammonia, use stopwatch to time, record mouse cough incubation period (s) and the number of coughs (times) in three minutes. The manifestation of cough is: when opening mouth wide or opening mouth slightly, with coughing sound, all visible abdominal muscle contraction.

[0113] Elimination criteria for mice with cough sensitivity: ① Coughing less than 10 times and more than 80 times within three minutes; ② Latency after spraying less than 15 seconds and more than 50 seconds; ③ Others: animals died, in poor condition, or had abnormally strong reactions; animals that met any of the three criteria were eliminated and not included in subsequent experiments.

[0114] (2) Effect of the composition on the mouse cough model induced by concentrated ammonia

[0115] 140 mice (73 females and 67 males) were screened out from 200 mice. The qualified animals were randomly divided into a control group, a positive group (codeine phosphate; dosage: 15 mg / kg), and a test group (syrup of application examples 1-3 and comparative application examples 1-9; dosage: 35 mg / kg) according to their body weight; each group had 10 mice. The drug-drug group (including the positive group and the test group) was gavaged with the corresponding drug solution (20 mL / kg, the solvent was normal saline), and the control group was gavaged with normal saline (20 mL / kg). The drug was administered 3 times, once a day. One hour after the last administration, 12.5 wt% ammonia water was used for stimulation, and the cough latency (s) and the number of coughs within three minutes (times) of the mice were recorded. Statistical methods: Data are expressed as mean ± standard deviation Statistical analysis was performed using SPSS 17.0 statistical analysis software, with one-way analysis of variance. P < 0.05 was considered statistically significant. Specific data are shown in Table 1.

[0116] Table 1 Effects of three doses of drug on the latency period (s) and the number of coughs within three minutes (times) of mice induced by ammonia

[0117]

[0118]

[0119] Note: Compared with the control group, *P<0.05, **P<0.01.

[0120] Experiment 2: Antiasthmatic effect test

[0121] Test reagents: histamine phosphate, aminophylline solution.

[0122] Experimental animals: 70 SPF guinea pigs (35 females and 35 males), weighing 450±50 g, were purchased from Guangdong Weitonglihua Experimental Animal Technology Co., Ltd.

[0123] Main instruments: ultrasonic nebulizer (purchased from Yuehua WH-2000).

[0124] Test method: Guinea pigs were randomly divided into a control group, a positive group (aminophylline solution, concentration of 12.5wt%) and a test group (Application Examples 1-3 and Comparative Application Examples 1-9, dosage: 35mg / kg), 5 in each group. The drug-treated groups (including the positive group and the test group) were gavaged with the corresponding drug solution (20mL / kg, solvent is normal saline), and the control group was gavaged with normal saline (20mL / kg). The drug was administered once a day for 3 consecutive days. One hour after the last administration, the guinea pigs inhaled 0.4v / v% histamine phosphate. The time from the onset of convulsions and falls of the guinea pigs was recorded as the incubation period (time from the start of spraying to the fall). The guinea pigs were observed for 6 minutes. If they did not fall within 6 minutes, it was counted as 360s.

[0125] Statistical methods: Data are expressed as mean ± standard deviation The statistical analysis was performed using SPSS 17.0 statistical analysis software and one-way analysis of variance. P < 0.05 was considered statistically significant.

[0126] Table 2 Effects of 3-day drug administration on the latency period (s) of histamine-induced asthma in mice

[0127]

[0128]

[0129] Note: Compared with the control group, *P<0.05, **P<0.01.

[0130] As shown in Table 1, in the animal model, Application Examples 1-3 (35 mg / kg) all had significant antitussive effects, and Application Example 1 had an effect similar to that of codeine phosphate. As shown in Table 2, when administered three times, Application Examples 1-3 all had a tendency to prolong the cough latency period, which was significantly different from the control group; Application Examples 1-3 and the positive group (codeine phosphate) significantly reduced the number of coughs within 3 minutes, which was significantly different from the control group.

[0131] Comparative Application Examples 1-3 are to explore the effects of enzymatic hydrolysis and fermentation of licorice, platycodon and scrophularia on the cough and asthma relieving properties of the composition. Combined with the data in Table 1-2, it can be seen that enzymatic hydrolysis and fermentation of licorice, platycodon and scrophularia and then compounding with cooked rehmannia, raw rehmannia, Radix Angelicae Sinensis, white peony root, fritillaria, ophiopogon and lily can have better cough and asthma relieving effects. This may be because enzymatic hydrolysis of licorice, platycodon and scrophularia can increase the dissolution of their active ingredients, and then using plant lactobacillus, utilis candida and cristatum to mix and ferment the enzymatic hydrolysate, which can increase the content of active ingredients, and rich secondary metabolites will be produced during the growth of microorganisms. These products will use the active ingredients or inactive ingredients of Chinese herbal medicines as precursors to produce new active ingredients through a variety of biotransformations, which have the effect of relieving cough and asthma from the aspects of anti-inflammatory, anti-oxidation and promoting absorption.

[0132] Comparative Application Examples 4-6 are intended to explore the effect of the selection of strains in the mixed bacteria on the antitussive and antiasthmatic properties of the composition. Combined with the data in Table 1-2, it can be seen that when Lactobacillus plantarum, Candida utilis, and Aspergillus niger are mixed and fermented, the antitussive and antiasthmatic effects of the composition can be synergistically improved. This may be because in the fermentation process using Lactobacillus plantarum, Candida utilis, and Aspergillus niger, the secondary metabolites of Lactobacillus plantarum can improve the biological barrier and enhance immunity; the secondary metabolites of Candida utilis have a positive effect on relieving cough and reducing inflammatory response; Aspergillus niger has good antioxidant function, which helps to protect the respiratory mucosa and reduce the inflammatory response caused by oxidative stress, thereby having a certain auxiliary effect on relieving cough, and the secondary metabolites of Aspergillus niger have certain antibacterial activity, which can inhibit or kill bacteria that cause respiratory infections and reduce coughs and other symptoms. The mixed fermentation of the above three strains can share metabolites, thereby achieving nutritional complementarity and synergistically improving the antitussive and antiasthmatic effects of the composition.

[0133] Comparative application examples 7-9 are intended to explore the effect of the dosage ratio of the mixed bacteria on the antitussive and antiasthmatic properties of the composition. Combined with the data in Table 1-2, it can be seen that when the mass ratio of Lactobacillus plantarum, Candida utilis, and Eurotium coronatum is within the range of 1:1:(2-4), the antitussive and antiasthmatic properties of the syrup can reach a better level.

[0134] Test 3: Hepatotoxicity and renal toxicity test

[0135] Test reagent: urethane.

[0136] Experimental animals: 40 KM mice (male), weighing 18±3 g, SPF grade, purchased from Guangdong Weitonglihua Experimental Animal Technology Co., Ltd.

[0137] Main instrument: optical microscope.

[0138] Experimental method: Mice were randomly divided into a control group and a test group (using the syrup of Example 1-3; dosage: 35 mg / kg), with 10 mice in each group. The drug-treated group (i.e., the test group) was gavaged with the corresponding drug solution (20 mL / kg, the solvent was normal saline), while the control group was gavaged with normal saline (20 mL / kg). The drug was administered for 7 consecutive days. The weight was weighed and recorded before administration. Before being sacrificed, the mice were fasted for 12 hours, weighed, and anesthetized by intraperitoneal injection of 15wt% urethane. Blood was collected from the abdominal aorta, and serum was separated. Four biochemical indices of seramine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (Cr) in each group of mice were measured. Mice were killed, and their livers and kidneys were removed. The liver coefficient and kidney coefficient were determined, respectively. Liver coefficient = liver mass / body mass × 100%, and kidney coefficient = kidney mass / body mass × 100%. Liver and kidney tissues were fixed with 4 v / v% formaldehyde solution, dehydrated conventionally, embedded in paraffin, sectioned, and stained with HE. The microstructure of the liver and kidney tissues was observed under a light microscope.

[0139] Statistical methods: Data are expressed as mean ± standard deviation The statistical analysis was performed using SPSS 17.0 statistical analysis software and one-way analysis of variance. P < 0.05 was considered statistically significant.

[0140] Table 3 Effects of the composition on the liver and kidney coefficients of mice

[0141]

[0142] Note: Compared with the control group, *P<0.05

[0143] As shown in Table 3, the pathological sections of application examples 1-3 were basically similar to those of the control group, with no obvious degeneration, necrosis or pathological abnormalities in liver and kidney cells. The various indexes were basically similar to those of the control group, with no significant differences.

[0144] In summary, the syrup prepared with the compound Fritillaria cirrhosa composition has a good effect of relieving cough and asthma, has no kidney toxicity to the human body, and is suitable for consumption by most people.

[0145] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. A compound Fritillaria cirrhosa cough-relieving composition, characterized in that: The Chinese medicine fermentation composition is prepared from the following raw materials in parts by weight: 10-15 parts of a Chinese medicinal fermentation composition, 7-10 parts of cooked rehmannia, 7-10 parts of raw rehmannia, 7-10 parts of Radix Angelicae Sinensis, 1-4 parts of white peony root, 10-15 parts of Fritillaria cirrhosa, 10-15 parts of Radix Ophiopogonis, and 10-15 parts of lily; wherein the Chinese medicinal fermentation composition comprises the following raw materials in parts by weight: 1-4 parts of Scrophularia ningpoensis, 1-4 parts of Platycodon grandiflorum, and 1-4 parts of Licorice root; The preparation method of the traditional Chinese medicine fermentation composition comprises the following steps: S1. Grind licorice, platycodon grandiflorum and Scrophularia ningpoensis to obtain a mixed powder; S2. Add 5-7 times the mass of deionized water to the mixed powder and stir evenly to obtain a mixed solution; S3, adding cellulase to the mixed solution for enzymolysis, wherein the amount of cellulase added is 5-7wt% of the mixed solution, the enzymolysis temperature is 30-35°C, and the enzymolysis time is 3-6h. After the enzymolysis is completed, filtering is performed to obtain an enzymolysis solution; S4. Adding glucose and peptone to the enzymatic hydrolysate, mixing well, sterilizing and filtering the enzymatic hydrolysate to obtain a filtrate; S5. Inoculating mixed bacteria into the filtrate for mixed fermentation, sterilizing at high temperature and filtering after the fermentation to obtain a Chinese medicine fermentation broth, concentrating the Chinese medicine fermentation broth, spray-drying and granulating it to obtain a granular Chinese medicine fermentation composition; wherein the mixed bacteria is a composition of Lactobacillus plantarum, Candida utilis, and Eurotium cristatum in a mass ratio of 1:1:(3-4), the total amount of bacteria added is 5-7wt% of the filtrate, the fermentation time is 12-16h, the fermentation temperature is 28-30°C, and the fermentation pH is 5.8-7.1; The preparation method of the compound Chuanbei cough-relieving composition comprises the following steps: (1) Mix Radix Angelicae Sinensis, Radix Paeoniae Alba, Lilium Bulb, Radix Ophiopogonis, and Fritillariae Cirrhosae Bulb, add 8-12 times the volume of 65-75% ethanol solution, and soak for 12-48 hours. Then, reflux and extract for 2-3 times, each time for 1-3 hours, and combine the extracts. (2) Mix the cooked and raw rehmannia roots, add 8-12 times the amount of water, and boil for 2-3 times, each time for 1-3 hours. Combine the decoctions. (3) The extract solution and the decoction solution are combined to obtain an extract solution, and the Chinese medicine fermentation composition is added thereto, stirred evenly, and concentrated to 0.5-1 times the amount of the corresponding raw medicine to obtain the compound Fritillaria cirrhosa cough-relieving composition.

2. A compound Chuanbei cough syrup, characterized in that: The invention comprises the compound Fritillaria cirrhosa cough relieving composition according to claim 1, sucrose and excipients; the mass ratio of the compound Fritillaria cirrhosa cough relieving composition, sucrose and excipients is (10-15): (80-90):

1.

3. The compound Chuanbei cough syrup according to claim 2, characterized in that The auxiliary material is a preservative.

4. The compound Chuanbei cough syrup according to claim 3, characterized in that The preservative is at least one of potassium sorbate, sodium benzoate and ethylparaben.

5. The method for preparing the compound Chuanbei cough syrup according to any one of claims 2 to 4, characterized in that: The following steps are involved: The compound Chuanbei cough relieving composition, sucrose, auxiliary materials and water are heated and stirred evenly, and then cooled to room temperature to obtain the compound Chuanbei cough relieving syrup.

6. The method for preparing the compound Chuanbei cough syrup according to claim 5, wherein: The heating and stirring temperature is 70-80° C., the time is 5-10 minutes, and the stirring speed is 200-300 rpm.

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