Compound bulbus fritilariae cough-relieving composition, syrup and preparation method thereof

Abstract

The invention relates to a compound bulbus fritilariae cough-relieving composition, syrup and a preparation method thereof, and belongs to the technical field of traditional Chinese medicines. The compound bulbus fritillariae cirrhosae cough-relieving composition is prepared from traditional Chinese medicine fermented particles, radix rehmanniae preparata, radix rehmanniae, radix angelicae sinensis, radix paeoniae alba, bulbus fritillariae cirrhosae, radix ophiopogonis and lilium brownii. The traditional Chinese medicine fermented particles are prepared from liquorice, platycodon grandiflorum and radix scrophulariae as raw materials through the following steps: firstly, carrying out enzymolysis on the raw materials by using cellulase to obtain enzymatic hydrolysate; the compound bulbus fritillariae cirrhosae cough-relieving composition is prepared by the following steps: performing enzymolysis on bulbus fritillariae cirrhosae, performing mixed fermentation on enzymatic hydrolysate by using lactobacillus plantarum, candida utilis and eurotium cristatum to obtain fermentation liquor, and performing sterilization, filtration, concentration and granulation on the mixed fermentation liquor to obtain traditional Chinese medicine fermentation granules, so that the obtained compound bulbus fritillariae cirrhosae cough-relieving composition has good effects of nourishing yin, moistening lung and relieving cough and asthma.

Description

Technical Field

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

[0002] Baihe Gujin Decoction is made of cooked rehmannia, raw rehmannia, Radix Angelicae Sinensis, white peony root, liquorice, platycodon, Scrophularia, Fritillaria, Ophiopogon japonicus, and lily. It is mainly used to treat lung and kidney yin deficiency and virtual fire inflammation. Cough and asthma, blood in sputum, dry and sore throat, dizziness, hot flashes in the afternoon, red tongue with little coating, and thin pulse. It is commonly used in the clinic to treat pulmonary tuberculosis, chronic bronchitis, bronchiectasis and hemoptysis, chronic pharyngitis, spontaneous pneumothorax, etc., which are caused by lung and kidney yin deficiency and virtual fire inflammation.

[0003] The traditional decoction preparation method of Chinese medicine does have some inconveniences and limitations. For example, different herbs and prescriptions require different decoction times, which need to be strictly followed according to the doctor's instructions, otherwise it may affect the efficacy of the medicine. When decocting the medicine, the heat needs to be adjusted according to the nature of the medicine. Usually, high heat is used before boiling, and low heat is used to maintain a slight boiling state after boiling, which may be difficult for non-professionals to master. In addition, general herbs can be decocted 2-3 times to ensure full utilization of the efficacy, but this also means that multiple operations are required, which is cumbersome and cannot be taken in time when symptoms appear. Summary of the invention

[0004] The purpose of the present invention is to overcome the shortcomings of the prior art and provide a composite Fritillaria cirrhosa cough suppressant composition, syrup and preparation method thereof, and to improve the process of the existing Chinese medicine formula by using multi-strain mixed fermentation to promote the improvement of the efficacy of the composition 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 composite Chuanbei cough-relieving composition, which is prepared from the following raw materials in parts by weight: 10-15 parts of a Chinese medicinal fermentation composition, 7-10 parts of Rehmannia glutinosa, 7-10 parts of Radix Rehmanniae glutinosae, 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 Lilium; 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;

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

[0008] S1, grinding liquorice, 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, stir evenly to obtain a mixed solution;

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

[0011] S4, adding glucose and peptone to the enzymatic hydrolysate, mixing evenly, 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] The syndrome of this prescription is caused by deficiency of lung and kidney yin. The lung is the mother of the kidney. Lung deficiency affects the kidney. Long-term illness leads to lung and kidney yin deficiency. Yin deficiency generates internal heat, virtual fire rises, and the lung fails to descend, resulting in cough and asthma. Virtual fire burns body fluids, resulting in dry and painful throat, hot flashes in the afternoon, and even burns the lung network, resulting in blood in sputum. The treatment should nourish the yin and blood of the lung and kidney, and clear away heat, resolve phlegm and relieve cough, taking into account both the diagram and the original. In the prescription, lily is sweet, bitter and slightly cold, nourishes yin, clears heat, moistens the lung and relieves cough; raw rehmannia and cooked rehmannia are used together to nourish the kidney and strengthen water, among which raw rehmannia can also cool blood and stop bleeding. The combination of the three medicines is a common combination of moistening the lung and nourishing the kidney, and replenishing both metal and water, and they are all monarch medicines. Ophiopogon japonicus is sweet and cold, and cooperates with lily to nourish yin and clear heat, moisten the lung and relieve cough; Scrophularia ningpoensis is salty and cold, and helps the two rehmannia to nourish yin and strengthen water, clear virtual fire, and benefit the throat, and they are all minister medicines. Angelica sinensis treats cough and shortness of breath, and white peony root nourishes and regulates blood; Fritillaria clears heat and moistens the lungs, resolves phlegm and relieves cough, and both are adjuvants. Platycodon grandiflorum clears the lungs and relieves sore throat, resolves phlegm and disperses knots, and carries the medicine upward; raw licorice clears heat and purges fire, and harmonizes the various medicines, and together they are adjuvants.

[0014] The invention selects liquorice, platycodon and scrophularia as raw materials, first uses cellulase to enzymolyze them to obtain enzymolysis solution, then uses plant lactobacillus, utilis and scutellaria baicalensis to mix and ferment the enzymolysis solution to obtain fermentation solution, and then sterilizes, filters, concentrates and granulates the mixed fermentation solution to obtain traditional Chinese medicine fermentation granules, wherein scutellaria baicalensis can transform and decompose phenolic substances in liquorice, platycodon and scrophularia baicalensis to generate 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 cough has a certain auxiliary effect, and the secondary metabolites of the crown-like cyst have certain antibacterial activity, which can inhibit or kill bacteria that cause respiratory infections, reduce coughs and other symptoms; the secondary metabolites of Lactobacillus plantarum can improve the biological barrier and enhance immunity; Candida utilis contains mannose and β-glucan, which have the function of immunostimulants, can stimulate or enhance the body's immune function, and Candida utilis and its secondary metabolites have a positive effect on cough relief and reducing inflammatory responses. The mixed fermentation of the above three strains can share metabolites, thereby achieving nutritional complementarity. In addition, Lactobacillus plantarum has a strong ability to decompose protein and can produce a variety of amino acids, providing nutrients for Candida utilis, and the metabolites of Candida utilis, such as pyruvic acid, 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 meshes.

[0017] Preferably, in step S4, the amount of glucose added is 9-12wt% of the enzymatic hydrolysate, and the amount of peptone added is 3wt% 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) Mix Radix Angelicae Sinensis, Radix Paeoniae Alba, Lilium Bulbs, Radix Ophiopogonis, and Fritillariae Cirrhosae Bulbs, add 8-12 times the amount of 65-75% ethanol solution by volume, and soak for 12-48 hours, then reflux and extract for 2-3 times, each time for 1-3 hours, and combine the extracts;

[0020] (2) After mixing cooked rehmannia and raw rehmannia, add 8-12 times the amount of water, decoct 2-3 times, each time for 1-3 hours, and combine the decoctions;

[0021] (3) The extract solution and the decoction solution are combined to obtain an extract solution, and then the Chinese medicine fermentation composition is added, stirred evenly, and concentrated to 0.5-1 times the amount of the corresponding raw medicine to obtain the compound Chuanbei cough-relieving 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 auxiliary materials; the mass ratio of the compound Fritillaria cirrhosa cough syrup, sucrose and auxiliary materials 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 Fritillaria cirrhosa cough syrup, comprising the following steps:

[0026] The compound Chuanbei cough relieving composition, sucrose, auxiliary materials and water are heated and stirred evenly, and 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 composite Chuanbei composition of the present invention is made of Chinese medicine fermented granules, cooked rehmannia, raw rehmannia, Radix Angelicae Sinensis, white peony root, Fritillaria cirrhosa, Radix Ophiopogonis and lily. The Chinese medicine fermented granules are made of licorice, platycodon and Scrophularia ningpoensis, and the raw materials are first enzymolyzed with cellulase to obtain an enzymolysis solution, and then the enzymolysis solution is mixed and fermented with Lactobacillus plantarum, Candida utilis and Eurotium coronariae to obtain a fermentation solution, and then the mixed fermentation solution is sterilized, filtered, concentrated and granulated to obtain 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 coronariae and cooked rehmannia, Radix Angelicae Sinensis, white peony root, Fritillaria cirrhosa, Radix Ophiopogonis and lily has a better antitussive and antiasthmatic 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 implementation schemes and do not constitute limitations on the protection scope of the present invention.

[0031] The experimental methods in the following examples without specifying specific conditions are usually carried out under conventional conditions or conditions recommended by the manufacturer. Unless otherwise specified, the calculation is based on mass percentage and mass fraction.

[0032] Some 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] Scrophularia: 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: purchased from Ningbo Mingzhou Biotechnology Co., Ltd., with the number BMZ142110.

[0047] Example 1

[0048] A composite Chuanbei cough-relieving composition, prepared from the following raw materials in parts by weight: 12 parts of a Chinese medicine fermentation composition, 9 parts of cooked rehmannia, 9 parts of raw rehmannia, 12 parts of Radix Angelicae Pubescentis, 3 parts of white peony root, 12 parts of Fritillariae Cirrhosae, 12 parts of Radix Ophiopogonis, and 12 parts of Lilium; wherein the Chinese medicine fermentation composition comprises the following raw materials in parts by weight: 3 parts of Scrophulariae, 2 parts of Platycodon grandiflorum, and 3 parts of Licorice;

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

[0050] S1, grinding liquorice, platycodon and scrophularia 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, stir evenly to obtain a mixed solution;

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

[0053] S4, adding 10wt% glucose and 3wt% peptone to the enzymatic hydrolyzate, mixing well, sterilizing at 105°C for 40min, and filtering 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 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 composite Fritillaria cirrhosa cough suppressant composition comprises the following steps:

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

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

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

[0059] Example 2

[0060] A composite Chuanbei cough-relieving composition, prepared from the following raw materials in parts by weight: 10 parts of a Chinese medicinal fermentation composition, 7 parts of Rehmannia glutinosa, 7 parts of Radix Rehmanniae glutinosae, 7 parts of Radix Angelicae Pubescentis, 1 part of White Peony Root, 10 parts of Fritillariae Bulbs, 10 parts of Radix Ophiopogonis, and 10 parts of Lilium; wherein the Chinese medicinal fermentation composition comprises the following raw materials in parts by weight: 1 part of Scrophulariae ningpoensis, 1 part of Platycodon grandiflorum, and 4 parts of Licorice;

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

[0062] S1, grinding liquorice, platycodon and scrophularia 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, stir evenly to obtain a mixed solution;

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

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

[0066] S5. Inoculate mixed bacteria into the filtrate for mixed fermentation, sterilize at high temperature and filter after the fermentation to obtain a 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 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 composite Fritillaria cirrhosa cough suppressant composition comprises the following steps:

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

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

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

[0071] Example 3

[0072] A composite Chuanbei cough-relieving composition, prepared from the following raw materials in parts by weight: 15 parts of a Chinese medicinal fermentation composition, 10 parts of cooked rehmannia, 10 parts of raw rehmannia, 10 parts of Radix Angelicae Sinensis, 4 parts of white peony root, 15 parts of Fritillariae tuber, 15 parts of Radix Ophiopogonis, and 15 parts of Lilium; wherein the Chinese medicinal fermentation composition comprises the following raw materials in parts by weight: 4 parts of Scrophulariae, 4 parts of Platycodon grandiflorum, and 1 part of Licorice;

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

[0074] S1, grinding liquorice, platycodon and scrophularia 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, stir evenly to obtain a mixed solution;

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

[0077] S4, adding 12wt% glucose and 3wt% peptone to the enzymatic hydrolyzate, mixing well, sterilizing at 105°C for 30min, and filtering to obtain a filtrate;

[0078] S5. Inoculate mixed bacteria into the filtrate for mixed fermentation, sterilize at high temperature and filter after the fermentation to obtain a 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 composite Fritillaria cirrhosa cough suppressant composition comprises the following steps:

[0080] (1) Radix Angelicae Sinensis, Radix Paeoniae Alba, Lilium Bulbs, Radix Ophiopogonis, and Fritillariae Chuanxiong were mixed, and then 12 times the volume of 75% ethanol solution was added to soak for 48 hours, and then refluxed for extraction for 3 times, each time for 3 hours, and the extracts were combined;

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

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

[0083] Comparative Example 1

[0084] The difference between Comparative Example 1 and Example 1 is that Scrophularia, Platycodon and Licorice are not subjected to steps S1 to S5, i.e., they are not subjected to enzymatic hydrolysis and fermentation treatments; Platycodon is subjected to alcohol extraction together with other alcohol-extracted components in step (1) of the preparation method of the composite Fritillaria cirrhosa cough suppressant composition; Scrophularia and Licorice are subjected to water extraction together with other water-extracted components in step (2) of the preparation method of the composite Fritillaria cirrhosa cough suppressant 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 of step S3.

[0087] Comparative Example 3

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

[0089] Comparative Example 4

[0090] The difference between Comparative Example 4 and Example 1 is that the total amount of 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, no Eurotium cristatum is 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 chuanbei cough syrup, sucrose, preservatives 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 chuanbei cough syrup.

[0106] Test 1: Cough 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 hot ultrasonic atomizer, add 40mL of freshly prepared ammonia solution (12.5wt%). Put the mouse into a beaker with a volume of 1000mL, seal the beaker mouth with plastic wrap, and open two openings (one for inserting the ultrasonic atomizer outlet pipe, and the other for ventilation holes). After the ultrasonic atomizer is continuously passed with ammonia for 60s at the minimum spray intensity, immediately close and quickly open the plastic wrap to allow the ammonia to diffuse naturally. While passing ammonia, use a stopwatch to time and record the mouse cough latency (s) and the number of coughs (times) within three minutes. The manifestation of coughing is: coughing when opening the mouth wide or small, and abdominal muscle contraction can be seen.

[0113] Elimination criteria for mouse cough sensitivity: ① Coughing less than 10 times and more than 80 times within three minutes; ② The incubation period after spraying is less than 15 seconds and more than 50 seconds; ③ Others: animal death, poor condition, abnormal reaction, etc.; Animals that meet any of the three conditions will be eliminated and will not be 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; 10 mice in each group. The drug-treated 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, the mice were stimulated with 12.5wt% ammonia water, 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 The statistical analysis was performed using SPSS 17.0 statistical analysis software, and one-way analysis of variance was used for analysis and statistics. P < 0.05 was considered statistically significant. Specific data are shown in Table 1.

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

[0117]

[0118]

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

[0120] Experiment 2: Antiasthmatic effect experiment

[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) according to their weight, with 5 in each group. The drug-dosing group (including the positive group and the test group) was intragastrically administered with the corresponding drug solution (20mL / kg, the solvent was normal saline), and the control group was intragastrically administered 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 were allowed to inhale 0.4v / v% histamine phosphate. The time from the start of spraying to the time of falling of the guinea pigs was recorded as the latent period (the time from the start of spraying to the time of falling). The observation was continued for 6min, and those who did not fall within 6min were counted as 360s.

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

[0126] Table 2 Effect 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 similar effects to codeine phosphate. As shown in Table 2, when the drug was 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 effect of licorice, platycodon and Scrophularia on the antitussive and antiasthmatic properties of the composition after enzymatic hydrolysis and fermentation. Combined with the data in Table 1-2, it can be seen that the enzymatic hydrolysis and fermentation of licorice, platycodon and Scrophularia and then compounded with cooked rehmannia, raw rehmannia, Radix Angelicae Sinensis, white peony, Fritillaria, Ophiopogon japonicus and lily can have better antitussive and antiasthmatic effects. This may be because enzymatic hydrolysis of licorice, platycodon and Scrophularia can increase the dissolution of their effective ingredients, and then using plant lactobacillus, utilis and crown-like cysts 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 effective ingredients or ineffective ingredients of Chinese herbal medicines as precursors, and produce new active ingredients through a variety of biotransformations, which have the effect of antitussive and antiasthmatic effects in terms of anti-inflammatory, anti-oxidation, and promoting absorption.

[0132] Comparative application examples 4-6 are to explore the influence 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 roxburghii are mixed and fermented, the antitussive and antiasthmatic effects of the composition can be synergistically improved. This may be because in the fermentation process of Lactobacillus plantarum, Candida utilis, and Aspergillus roxburghii, 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 roxburghii 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 roxburghii have certain antibacterial activity, which can inhibit or kill bacteria that cause respiratory infections, reduce cough and other symptoms, and 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 Tables 1-2, it can be seen that when the mass ratio of Lactobacillus plantarum, Candida utilis, and Eurotium coronarius 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: Hepato-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 (syrup of application example 1-3; dosage: 35 mg / kg) according to body weight, 10 mice in each group. The drug administration group (i.e., the test group) was intragastrically administered with the corresponding drug solution (20 mL / kg, the solvent was normal saline), and the control group was intragastrically administered with normal saline (20 mL / kg), and the drug administration was continued for 7 days. The weight was weighed and recorded before administration, and the mice were fasted for 12 hours before being killed, weighed, anesthetized by intraperitoneal injection of 15wt% urethane, blood was collected from the abdominal aorta, serum was separated, and four biochemical indices of seramine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (BUN), and creatinine (Cr) of mice in each group were determined. The mice were killed, and the liver and kidneys were taken out to determine the liver coefficient and kidney coefficient, respectively. The liver coefficient = liver mass / body mass × 100%, and the kidney coefficient = kidney mass / body mass × 100%. The liver and kidney tissues were fixed with 4v / 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 method: Data are presented as mean ± standard deviation The statistical analysis was performed using SPSS 17.0 statistical analysis software, and one-way analysis of variance was used for analysis and statistics. 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 of liver and kidney cells. The indexes were basically similar to those of the control group, with no significant differences.

[0144] In summary, the syrup prepared with the composite 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 solution of the present invention rather than to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solution of the present invention can be modified or replaced by equivalents without departing from the essence and scope of the technical solution of the present invention.

Claims

1. A composite Fritillaria cirrhosa cough suppressant composition, characterized in that: The Chinese medicine fermentation composition is prepared from the following raw materials in parts by weight: 10-15 parts of 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 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; The preparation method of the traditional Chinese medicine fermentation composition comprises the following steps: S1, grinding liquorice, platycodon grandiflorum and scrophularia ningpoensis to obtain a mixed powder; S2. Add 5-7 times the mass of deionized water to the mixed powder, 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, the enzymolysis time is 3-6h, and after the enzymolysis is completed, filtering is performed to obtain an enzymolysis solution; S4, adding glucose and peptone to the enzymatic hydrolysate, mixing evenly, sterilizing and filtering the enzymatic hydrolysate to obtain a filtrate; 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.

2. The composite Chuanbei antitussive composition according to claim 1, characterized in that: In step S5 of preparing the traditional Chinese medicine fermentation composition, the mass ratio of Lactobacillus plantarum, Candida utilis, and Eurotium cristatum is 1:1:(3-4).

3. The method for preparing the composite Fritillaria cirrhosa cough suppressant composition according to claim 1 or 2, characterized in that: The following steps are involved: (1) Mix Radix Angelicae Sinensis, Radix Paeoniae Alba, Lilium Bulbs, Radix Ophiopogonis, and Fritillariae Cirrhosae Bulbs, add 8-12 times the amount of 65-75% ethanol solution by volume, 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) After mixing cooked rehmannia and raw rehmannia, add 8-12 times the amount of water, decoct 2-3 times, each time for 1-3 hours, and combine the decoctions; (3) The extract solution and the decoction solution are combined to obtain an extract solution, and then the Chinese medicine fermentation composition is added, stirred evenly, and concentrated to 0.5-1 times the amount of the corresponding raw medicine to obtain the compound Chuanbei cough-relieving composition.

4. A compound Chuanbei cough syrup, characterized in that: The invention comprises the compound Fritillaria chuanxiong cough suppressant composition as claimed in claim 1 or 2, sucrose and auxiliary materials; the mass ratio of the compound Fritillaria chuanxiong cough suppressant composition, sucrose and auxiliary materials is (10-15):(80-90):

1.

5. The compound Chuanbei cough syrup according to claim 4, characterized in that: The auxiliary material is a preservative.

6. The compound Chuanbei cough syrup according to claim 5, characterized in that: The preservative is at least one of potassium sorbate, sodium benzoate and ethylparaben.

7. The method for preparing the compound Chuanbei cough syrup according to any one of claims 4 to 6, 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 cooled to room temperature to obtain the compound Chuanbei cough relieving syrup.

8. The method for preparing the compound Chuanbei cough syrup according to claim 7, characterized in that: 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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