Application of Yun Weiling volatile oil in preparation of digestion-aiding and appetite-stimulating drugs

Abstract

The application discloses application of cloud weiling volatile oil in preparation of digestion-aiding and appetite-stimulating drugs. A preparation method of the cloud weiling volatile oil is as follows: cloud weiling medicinal materials are crushed, 8-10 times of water is added, and the mixture is refluxed at 90-100 DEG C for 3-5 hours, then the cloud weiling volatile oil is collected by a volatile oil extractor, dehydrated by adding anhydrous sodium sulfate, centrifuged, filtered, and obtained. The application provides application of the cloud weiling volatile oil in preparation of digestion-aiding and appetite-stimulating drugs. Experiments prove that the cloud weiling volatile oil can promote intestinal peristalsis, promote secretion of GAS and MTL, enhance pepsin activity and secretion, and increase food intake, and has the prospect of becoming a digestion-aiding and appetite-stimulating drug.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine extract technology, specifically relating to the application of Yunweiling volatile oil in the preparation of digestive aids and appetite stimulants. Background Technology

[0002] In recent years, people have experienced an increasing number of cases of poor digestion or loss of appetite due to stress, irregular eating habits, and unhealthy diets. Therefore, it is extremely necessary to find highly effective, low-toxicity drugs that address both the symptoms and root cause of these problems to promote digestion and enhance appetite.

[0003] "Yunweiling" refers to Inula japonica, a plant belonging to the genus Inula in the family Asteraceae. Inula nervosa The dried roots and rhizomes of *Inula japonica* (also known as "Mao Xiucai," "Xiao Hei Yao," "Hei Weiling," and "Macale Bing") are mainly distributed in Yunnan, Sichuan, Guizhou, Guangxi, and Hunan provinces. Yunweiling has a long history of being used as both food and medicine in Yunnan. In 2010, the Ministry of Health approved *Inula japonica* (Yunweiling) as a new resource food, using its dried rhizomes as raw material, which are selected, cleaned, dried, and mechanically pulverized to produce a common food (condiment). As a new resource food, the food processing methods for this product on the market are simple, and its applications are limited. With the continuous upgrading of consumer demand, the improvement of consumer awareness, and the pursuit of healthy eating, Yunweiling, as a new resource food, has enormous potential and market prospects.

[0004] The present invention aims to provide a Yunweiling extract that can aid digestion and stimulate appetite. Summary of the Invention

[0005] The purpose of this invention is to provide the application of Yunweiling volatile oil in the preparation of digestive aids and appetite stimulants.

[0006] The objective of this invention is achieved by applying Yunweiling volatile oil in the preparation of digestive aids and appetite stimulants. The preparation method of the Yunweiling extract is as follows: Take Yunweiling medicinal material, pulverize it, add 8-10 times the amount of water, reflux and extract for 3-5 hours, collect the extract using a volatile oil extractor, add anhydrous sodium sulfate for dehydration, centrifuge, and filter to obtain Yunweiling volatile oil.

[0007] The beneficial effects of this invention are as follows: This invention provides the application of Yunweiling volatile oil in the preparation of digestive aid and appetite stimulating drugs. Experiments have shown that Yunweiling volatile oil can promote intestinal peristalsis, promote the secretion of GAS and MTL, enhance pepsin activity and promote pepsin secretion, and increase food intake. Among them, the pepsin activity of Yunweiling volatile oil is better than that of the positive control group, and it has the potential to become a digestive aid and appetite stimulating drug. Attached Figure Description

[0008] Figure 1The effect of Yunweiling volatile oil prepared in Example 1 on the small intestinal propulsion rate (left figure) and small intestinal propulsion rate in mice.

[0009] Effect diagram of the transformation value (right figure) (#### indicates comparison with the normal group) P <0.0001; * indicates comparison with the model group. P <0.05; ** indicates comparison with the model group. P <0.01; **** indicates comparison with the model group. P <0.0001.

[0010] Figure 2 The effect of Yunweiling volatile oil prepared in Example 1 on the secretion of GAS (left) and MTL (right) in mouse serum (#### indicates comparison with the normal group) is shown in the figure. P <0.0001; * indicates comparison with the model group. P <0.05; ** indicates comparison with the model group. P <0.01; **** indicates comparison with the model group. P <0.0001.

[0011] Figure 3 The effect of Yunweiling volatile oil prepared in Example 1 on pepsin activity (left) and pepsin excretion (right) in rats (* indicates comparison with the normal group). P <0.05; ** indicates comparison with the normal group P <0.01; *** indicates comparison with the normal group P <0.001; **** indicates comparison with the normal group P <0.0001.

[0012] Figure 4 The graph shows the effect of the drug compositions prepared in Example 5 and Comparative Example 1 on the small intestinal propulsion rate (left) and the small intestinal propulsion rate conversion value (right) in mice (compared with the normal group). ## P <0.01; Compared with the model group: ** P <0.01 *** P <0.001 **** P <0.0001);

[0013] Figure 5 The graph shows the effect of the drug compositions prepared in Example 5 and Comparative Example 1 on pepsin activity (left) and pepsin excretion (right) in rats (compared to the normal group). * P <0.05 ** P <0.01*** P <0.001 **** P <0.0001). Detailed Implementation

[0014] The present invention will be further described below, but this is not intended to limit the invention in any way. Any modifications made based on the present invention are within the scope of protection of the present invention.

[0015] This invention provides the application of Yunweiling volatile oil in the preparation of digestive aids and appetite stimulants. The preparation method of the Yunweiling extract is as follows: Yunweiling medicinal material is taken, pulverized, and 8-10 times the amount of water is added. The mixture is refluxed for 3-5 hours, collected using a volatile oil extractor, dehydrated with anhydrous sodium sulfate, centrifuged, and filtered to obtain Yunweiling volatile oil.

[0016] The present invention also provides a pharmaceutical composition comprising the Yunweiling volatile oil and a pharmaceutically acceptable carrier.

[0017] The present invention further provides a traditional Chinese medicine composition based on the volatile oil of Yunweiling, which aids digestion and stimulates appetite. The composition comprises the following raw materials in parts by weight: 10-20 parts Yunweiling, 10-20 parts Poria cocos, 5-15 parts Citrus reticulata peel, 5-15 parts charred hawthorn, 5-15 parts roasted malt, and 5-10 parts Amomum villosum; the volatile oil of Yunweiling is extracted from Yunweiling.

[0018] The pharmaceutical composition is prepared by adding medically acceptable excipients to form any one of the following: decoction, pill, ointment, syrup, granule, tablet, and capsule.

[0019] The preparation method of the decoction is as follows:

[0020] 1) Take Yunweiling powder, add 8-10 times the weight of water and reflux for 3-5 hours. Collect the volatile oil through a volatile oil extractor, dehydrate to obtain Yunweiling volatile oil, and keep the Yunweiling residue and the refluxed Yunweiling aqueous solution for later use.

[0021] 2) Add 6-8 times the amount of water to the Poria cocos, tangerine peel, charred hawthorn, stir-fried malt, and Amomum villosum, and decoct for 20-40 minutes with the Yunweiling medicine residue after distillation in step 2). Then add 4-8 times the amount of water to the decoction residue and decoct for 20-40 minutes. Mix the two decoctions together.

[0022] 3) Mix the Yunweiling aqueous solution obtained in step 1) with the decoction obtained in step 2), then add the volatile oil obtained in step 1), mix thoroughly, and the decoction is obtained.

[0023] The preparation method of the pills is as follows:

[0024] 1) Take Yunweiling powder, add 8-10 times the weight of water and reflux for 3-5 hours. Collect the volatile oil through a volatile oil extractor, dehydrate to obtain Yunweiling volatile oil, and keep the Yunweiling residue and the refluxed Yunweiling aqueous solution for later use.

[0025] 2) Add 6-8 times the amount of water to the Poria cocos, tangerine peel, charred hawthorn, stir-fried malt, and Amomum villosum, and decoct for 20-40 minutes with the Yunweiling medicine residue after distillation in step 2). Then add 4-8 times the amount of water to the decoction residue and decoct for 20-40 minutes. Mix the two decoctions together.

[0026] 3) Mix the Yunweiling aqueous solution obtained in step 1) with the decoction obtained in step 2), concentrate it to an extract of 1.5-2 g / ml, add the volatile oil obtained in step 1), add an appropriate amount of excipients, mix thoroughly, and then make into pills with water to obtain pills.

[0027] The preparation method of the granules is as follows:

[0028] 1) Take Yunweiling powder, add 8-10 times the weight of water and reflux for 3-5 hours. Collect the volatile oil through a volatile oil extractor, dehydrate to obtain Yunweiling volatile oil, and keep the Yunweiling residue and the refluxed Yunweiling aqueous solution for later use.

[0029] 2) Weigh out 10-20 g β - Add cyclodextrin to a 50 mL beaker, add 10-25 mL of anhydrous ethanol, stir and dissolve at 45-65℃, then add the Yunweiling volatile oil obtained in step 1) dropwise, maintain 45-65℃, stir at 300-900 r / min for 1.5-2.5 h, concentrate and dry under reduced pressure at 40℃, wash 3 times with petroleum ether, and evaporate to constant mass at room temperature to obtain the Yunweiling volatile oil inclusion complex;

[0030] 3) Add 6-8 times the amount of water to the distilled residue of Yunweiling in step 1) and decoct for 20-40 minutes. Then add 4-8 times the amount of water to the decocted residue and decoct for 20-40 minutes. Mix the two decoctions together.

[0031] 4) Mix the Yunweiling aqueous solution obtained in step 1) with the decoction obtained in step 3), concentrate and dry into powder, then add the volatile oil inclusion complex obtained in step 2), mix thoroughly and pass through a 100-mesh sieve to obtain a mixture, add an appropriate amount of 70%~90% ethanol, wet granulate, and dry to obtain granules.

[0032] Example 1

[0033] Weigh 100 g of Yunweiling medicinal material, place it in a round-bottom flask, connect it to a volatile oil extractor, add 800 mL of water, soak for 30 min, reflux at 95℃ once, each time for 4 h, collect the yellow volatile oil through the volatile oil extractor, add 10% anhydrous sodium sulfate, centrifuge, and remove the upper yellow oily substance to obtain 0.5 ml of volatile oil extract.

[0034] Example 2

[0035] Weigh 100 g of Yunweiling medicinal material, place it in a round-bottom flask, connect it to a volatile oil extractor, add 1000 mL of water, soak for 30 min, reflux at 90℃ once, each time for 4 h, collect the yellow volatile oil through the volatile oil extractor, add 10% anhydrous sodium sulfate, centrifuge, and remove the upper yellow oily substance to obtain 0.5 ml of volatile oil extract.

[0036] Example 3

[0037] Weigh 100 g of Yunweiling medicinal material, place it in a round-bottom flask, connect it to a volatile oil extractor, add 800 mL of water, soak for 30 min, reflux at 100℃ once, each time for 5 h, collect the yellow volatile oil through the volatile oil extractor, add 10% anhydrous sodium sulfate, centrifuge, and remove the upper yellow oily substance to obtain 0.48 ml of volatile oil extract.

[0038] Example 4

[0039] Weigh 100 g of Yunweiling sample medicinal material, place it in a round-bottom flask, connect it to a volatile oil extractor, add 800 mL of water, soak for 30 min, reflux at 90℃-100℃ once, each time for 3 h, collect the yellow volatile oil through the volatile oil extractor, add 10% anhydrous sodium sulfate, centrifuge, and aspirate the upper yellow oily substance to obtain 0.47 ml of volatile oil extract.

[0040] Example 5

[0041] Formula: Yunweiling 15g, Poria 15g, Tangerine peel 10g, Roasted hawthorn 10g, Fried malt 10g, Amomum villosum 5g.

[0042] Preparation method: 1. Take Yunweiling powder, add 8 times the weight of water and reflux at 90℃ for 4 hours. Collect the volatile oil through a volatile oil extractor and dehydrate to obtain Yunweiling volatile oil. The refluxed residue and the refluxed Yunweiling aqueous solution are used for later use.

[0043] 2. Add 8 times the amount of water to the Poria cocos, dried tangerine peel, charred hawthorn, stir-fried malt, and Amomum villosum, along with the Yunweiling residue from step A (distilled in step A), and decoct for 30 minutes. Then, add 6 times the amount of water to the remaining residue and decoct for another 30 minutes. Mix the two decoction solutions with the Yunweiling solution obtained in step 1, concentrate to 170-400 mg / ml, add the volatile oil obtained in step 1, and mix thoroughly to obtain 80.87 ml of decoction.

[0044] Example 6

[0045] Formula: Yunweiling 10g, Poria 10g, Tangerine peel 5g, Roasted hawthorn 5g, Fried malt 5g, Amomum villosum 5g.

[0046] Preparation method: 1. Take Yunweiling powder, add 8 times the weight of water and reflux at 100℃ for 4 hours. Collect the volatile oil through a volatile oil extractor and dehydrate to obtain Yunweiling volatile oil. The refluxed residue and the refluxed Yunweiling aqueous solution are used for later use.

[0047] 2. Add 8 times the amount of water to the Poria cocos, dried tangerine peel, charred hawthorn, stir-fried malt, and Amomum villosum, along with the Yunweiling dregs distilled in step 1, and decoct for 30 minutes. Then, add 6 times the amount of water to the decocted dregs and decoct for another 30 minutes. Mix the two decoction solutions with the Yunweiling aqueous solution obtained in step 1, concentrate to 170-400 mg / ml, add the volatile oil obtained in step 1, and mix thoroughly to obtain 49.77 ml of decoction.

[0048] Example 7

[0049] Formula: Yunweiling 20g, Poria 20g, Tangerine peel 15g, Roasted hawthorn 15g, Fried malt 15g, Amomum villosum 10g.

[0050] Preparation method: 1. Take Yunweiling powder, add 8 times the weight of water and reflux at 90℃ for 4 hours. Collect the volatile oil through a volatile oil extractor and dehydrate to obtain Yunweiling volatile oil. The refluxed residue and the refluxed Yunweiling aqueous solution are used for later use.

[0051] 2. Add 8 times the amount of water to the Poria cocos, dried tangerine peel, charred hawthorn, stir-fried malt, and Amomum villosum, along with the Yunweiling residue from step 1 (distilled), and decoct for 30 minutes. Then, add 6 times the amount of water to the remaining residue and decoct for another 30 minutes. Mix the two decoction solutions with the Yunweiling solution obtained in step 1, concentrate to 170-400 mg / ml, add the volatile oil obtained in step 1, and mix thoroughly to obtain 118.20 ml of decoction.

[0052] Example 8

[0053] Formula: Yunweiling 20g, Poria 15g, Tangerine peel 10g, Roasted hawthorn 10g, Fried malt 10g, Amomum villosum 8g.

[0054] Preparation method: 1. Take Yunweiling powder, add 8 times the weight of water and reflux at 95°C for 4 hours. Collect the volatile oil through a volatile oil extractor and dehydrate to obtain Yunweiling volatile oil. The refluxed residue and the refluxed Yunweiling aqueous solution are used for later use.

[0055] 2. Add 8 times the amount of water to the Poria cocos, dried tangerine peel, charred hawthorn, stir-fried malt, and Amomum villosum, along with the Yunweiling residue from step 1, and decoct for 30 minutes. Then, add 6 times the amount of water to the remaining residue and decoct for another 30 minutes. Mix the two decoction solutions with the Yunweiling solution obtained in step 1, concentrate to 170-400 mg / ml, add the volatile oil obtained in step 1, and mix thoroughly to obtain 90.83 ml of decoction.

[0056] Example 9

[0057] Formula: Yunweiling 15g, Poria 15g, Tangerine peel 10g, Roasted hawthorn 10g, Fried malt 10g, Amomum villosum 5g.

[0058] Preparation method: 1. Take Yunweiling powder, add 8 times the weight of water and reflux at 90℃ for 4 hours. Collect the volatile oil through a volatile oil extractor and dehydrate to obtain Yunweiling volatile oil. The refluxed residue and the refluxed Yunweiling aqueous solution are used for later use.

[0059] 2. Weigh 10 g of β-cyclodextrin into a 50 mL beaker, add 20 mL of anhydrous ethanol, stir and dissolve at 55 °C, then add the Yunweiling volatile oil obtained in step 1 dropwise, maintain 55 °C, stir at 500 r / min for 2 h, concentrate and dry under reduced pressure at 40 °C, wash 3 times with petroleum ether, and evaporate to constant mass at room temperature to obtain the Yunweiling volatile oil inclusion complex.

[0060] 3. Add 8 times the amount of water to the Poria cocos, dried tangerine peel, charred hawthorn, stir-fried malt, and Amomum villosum, along with the Yunweiling residue from step 1 (distilled), and decoct for 30 minutes. Then, add 6 times the amount of water to the remaining residue and decoct for another 30 minutes. Mix the two decoction solutions with the Yunweiling aqueous solution obtained in step 1, concentrate, and dry into a powder. Add the volatile oil inclusion complex obtained in step 2, mix thoroughly, and pass through a 100-mesh sieve to obtain the mixture. Add an appropriate amount of 70% ethanol, wet granulate, and dry to obtain granules.

[0061] Example 10

[0062] Formula: Yunweiling 10g, Poria 10g, Tangerine peel 5g, Roasted hawthorn 5g, Fried malt 5g, Amomum villosum 5g.

[0063] Preparation method: 1. Take Yunweiling powder, add 8 times the weight of water and reflux at 95°C for 4 hours. Collect the volatile oil through a volatile oil extractor and dehydrate to obtain Yunweiling volatile oil. The refluxed residue and the refluxed Yunweiling aqueous solution are used for later use.

[0064] 4. Weigh 10 g of β-cyclodextrin into a 50 mL beaker, add 20 mL of anhydrous ethanol, stir and dissolve at 55 °C, then add the Yunweiling volatile oil obtained in step 1 dropwise, maintain 55 °C, stir at 500 r / min for 2 h, concentrate and dry under reduced pressure at 40 °C, wash 3 times with petroleum ether, and evaporate to constant mass at room temperature to obtain the Yunweiling volatile oil inclusion complex.

[0065] 3. Add 8 times the amount of water to the Poria cocos, dried tangerine peel, charred hawthorn, stir-fried malt, and Amomum villosum, along with the Yunweiling residue from step 1 (distilled), and decoct for 30 minutes. Then add 6 times the amount of water to the remaining residue and decoct for another 30 minutes. Mix the two decoction solutions with the Yunweiling aqueous solution obtained in step 1, concentrate, and dry into powder. Add the volatile oil inclusion complex obtained in step 2, mix thoroughly, and pass through a 100-mesh sieve to obtain the mixture. Add an appropriate amount of 70% ethanol, wet granulate, and dry to obtain granules.

[0066] Example 11

[0067] Formula: Yunweiling 20g, Poria 20g, Tangerine peel 15g, Roasted hawthorn 15g, Fried malt 10g, Amomum villosum 10g.

[0068] Preparation method: 1. Take Yunweiling powder, add 8 times the weight of water and reflux at 90℃ for 4 hours. Collect the volatile oil through a volatile oil extractor and dehydrate to obtain Yunweiling volatile oil. The refluxed residue and the refluxed Yunweiling aqueous solution are used for later use.

[0069] 5. Weigh 10 g of β-cyclodextrin into a 50 mL beaker, add 20 mL of anhydrous ethanol, stir and dissolve at 55 °C, then add the Yunweiling volatile oil obtained in step 1 dropwise, maintain 55 °C, stir at 500 r / min for 2 h, concentrate and dry under reduced pressure at 40 °C, wash 3 times with petroleum ether, and evaporate to constant mass at room temperature to obtain the Yunweiling volatile oil inclusion complex.

[0070] 3. Add 8 times the amount of water to the Poria cocos, dried tangerine peel, charred hawthorn, stir-fried malt, and Amomum villosum, along with the Yunweiling residue from step 1 (distilled), and decoct for 30 minutes. Then, add 6 times the amount of water to the remaining residue and decoct for another 30 minutes. Mix the two decoction solutions with the Yunweiling aqueous solution obtained in step 1, concentrate, and dry into a powder. Add the volatile oil inclusion complex obtained in step 2, mix thoroughly, and pass through a 100-mesh sieve to obtain the mixture. Add an appropriate amount of 70% ethanol, wet granulate, and dry to obtain granules.

[0071] Example 12

[0072] Formula: Yunweiling 15g, Poria 15g, Tangerine peel 10g, Roasted hawthorn 10g, Fried malt 10g, Amomum villosum 5g.

[0073] Preparation method: 1. Take Vernonia patula, crush it, add 8 times the weight of water, reflux and extract at 100 °C for 4 hours, collect the volatile oil through a volatile oil extractor, dehydrate to obtain the volatile oil of Vernonia patula, and reserve the medicinal residues after reflux and the aqueous solution of Vernonia patula after reflux;

[0074] 2. Add Poria cocos, Citrus reticulata Blanco, Hawthorn Fruit (Fried), Germinated Barley (Fried), Amomum villosum and the medicinal residues of Vernonia patula after distillation in step 1) to 6 times the amount of water, decoct for 30 min, then add the medicinal residues after decoction to 4 times the amount of water and decoct for 30 min, and mix the two decoction solutions;

[0075] 3) Mix the aqueous solution of Vernonia patula obtained in step 1) with the decoction solution obtained in step 2), concentrate to an extract of 1.5 - 2 g / ml, then add the volatile oil obtained in step 1), add appropriate excipients, mix well, and make pills with water to obtain the pill preparation.

[0076] Control Example 1

[0077] Formulation: 15 g of Vernonia patula, 15 g of Poria cocos, 10 g of Citrus reticulata Blanco, 10 g of Hawthorn Fruit (Fried), 10 g of Germinated Barley (Fried), 5 g of Amomum villosum.

[0078] Preparation method: Add Vernonia patula, Poria cocos, Citrus reticulata Blanco, Hawthorn Fruit (Fried), Germinated Barley (Fried), Amomum villosum to 8 times the amount of water, decoct for 30 min, add the medicinal residues after decoction to 6 times the amount of water and decoct for 30 min, mix the two aqueous decoction solutions and the aqueous solution of Vernonia patula obtained in step 1), concentrate to 170 - 400 mg / ml, mix well to obtain the decoction preparation.

[0079] Experimental Example 1 Detection of the function of promoting digestion and increasing appetite of the volatile oil of Vernonia patula prepared by the present invention

[0080] I. Experimental method

[0081] 1. Experimental animals: SPF - grade male KM mice, body weight 18 - 22 g, 6 - week - old; SPF - grade male SD rats, body weight 120 - 150 g, 8 - week - old; both were purchased from Beijing Spepharm Biotechnology Co., Ltd., production license number SCXK(Beijing)2019 - 0010, and raised in SPF - grade environment, with indoor temperature of 22 - 25 °C.

[0082] 2. Drugs and reagents: Jianweixiaoshi tablets, batch number 22072065, Jiangzhong Pharmaceutical Co., Ltd.; Loperamide Hydrochloride Capsules, batch number LHJ5501, Janssen Pharmaceutical Co., Ltd.; activated carbon, Aladdin Reagent (Shanghai) Co., Ltd., the volatile oil of Vernonia patula prepared in Example 1

[0083] Loperamide Hydrochloride: 2.5 mg / kg;

[0084] 3. Model establishment, grouping and drug administration

[0085] Preparation of the modeling agent: Loperamide hydrochloride capsules were taken, the capsule shells were removed, and the powder was dissolved in 0.5% CMC-Na to prepare a suspension with a concentration of 2.5 mg / kg. On the last day of the experiment, the model group, the positive control group of Jianwei Xiaoshi tablets, and each treatment group were administered the modeling agent by gavage at a volume of 10 ml / kg.

[0086] Preparation of carbon powder indicator: Add 10 g of gum arabic to 80 mL of water and boil until transparent. Add 5 g of carbon powder to the above solution and boil three times. After cooling, bring the volume to 100 mL to obtain the carbon powder indicator.

[0087] Sixty SPF-grade male KM mice were acclimatized for 3-5 days and then randomly divided into 6 groups (n = 8) according to body weight: normal group, model group, positive control group of digestive tablets (940 mg / kg), and volatile oil groups from Example 1 (low (3.3 mg / kg), medium (6.5 mg / kg), and high dose (13 mg / kg)). The drug dosage for each group was 10 mL / kg. After 15 days of continuous administration, the small intestinal propulsion function of the mice was measured.

[0088] Forty SPF-grade male SD rats were acclimatized for 3-5 days and then randomly divided into 5 groups (n = 6) according to body weight: a normal control group, a positive control group for digestive tablets (1.33 g / kg), and three groups receiving the volatile oil from Example 1 (low (2.5 mg / kg), medium (5 mg / kg), and high dose (10 mg / kg)). The administration volume for each group was 10 mL / kg. The rats were administered the drug continuously for 30 days. Food intake was recorded at 9:00 AM, and body weight was measured twice a week. At the end of the experiment, body weight was recorded, and the weight gain, food utilization rate, total food intake, and pepsin digestive enzyme levels were calculated.

[0089] 4. Observation indicators:

[0090] 4.1 Determination of small intestinal propulsion rate

[0091] Before the end of the experiment, mice were fasted for 16 hours but allowed free access to water. On the last day of the experiment, the normal group and the model group were administered 0.5% CMC-Na solution by gavage, while the drug administration groups were administered the corresponding drugs by gavage. 30 minutes later, the normal group was administered 0.5% CMC-Na solution by gavage, while the model group, positive control group, and drug administration groups were administered the modeling agent by gavage. 30 minutes later, each group was administered carbon indicator by gavage. 25 minutes later, the mice were sacrificed, the abdominal cavity was opened, the mesentery was separated, and the small intestine from the upper end of the pylorus to the ileocecal junction was taken. The small intestine was straightened and placed on white paper, and the total length of the small intestine and the distance from the pylorus to the carbon indicator were measured. The carbon propulsion rate and the carbon propulsion rate conversion value were calculated.

[0092]

[0093]

[0094] Note: P - Small intestinal carbon propulsion rate

[0095] 4.2 Determination of motilin and gastrin in mouse serum

[0096] Blood from each group of mice was centrifuged at 4°C and 3500 rpm for 15 minutes. The supernatant was collected, and the levels of gastrin (GAS) and motilin (MTL) were detected using enzyme-linked immunosorbent assay (ELISA). The experimental procedures were strictly performed according to the kit instructions.

[0097] 4.3 Determination of rat body weight, body weight gain, food intake, and food utilization rate

[0098] After 30 days of gavage administration to rats, the weight gain, food intake, and food utilization rate were calculated.

[0099]

[0100] 4.4 Determination of pepsin and pepsin excretion in rats

[0101] Before the end of the experiment, rats were fasted but allowed free access to water for 24 hours. On the last day of the experiment, rats were anesthetized with sodium pentobarbital. The pylorus of the rats was ligated for 2 hours using the pyloric ligation method, and gastric juice was collected and its volume was measured. 15 mL of 0.05 mol / L HCl solution was added to each mL of the collected gastric juice and placed in a centrifuge tube. Two freshly prepared protein tubes were added, sealed, and incubated at 37 ℃ for 24 hours. The tubes were then removed, and the length (mm) of the transparent part at both ends of each protein tube was measured with vernier calipers. The average value of the four ends was calculated, and the pepsin activity was calculated according to the formula for pepsin activity units.

[0102] Pepsin activity units (U / mL) = (mean length of the transparent portion of the four-end protein tube) × 16

[0103] Pepsin excretion (U / h) = Pepsin activity × Gastric juice volume per hour

[0104] 5. Data Statistics and Analysis

[0105] All experimental data are expressed as averages. Standard deviation ( S) indicates that the data was statistically processed and analyzed using data software, and comparisons between the two groups were performed using... t For comparisons among multiple groups, one-way ANOVA was used to test the variance. P <0.05 is considered statistically significant.

[0106] II. Results Analysis

[0107] 1. Effects of small intestinal propulsion rate and small intestinal propulsion rate conversion value in mice

[0108] from Figure 1 It can be seen that after modeling, the small intestinal propulsion rate and small intestinal propulsion conversion value of the mice were significantly reduced. P <0.0.1), after drug treatment, the small intestinal propulsion rate and small intestinal transit value were significantly improved, and the small intestinal propulsion rate increased with increasing dose, which was statistically significant compared with the model group. P <0.01).

[0109] 2. Effects of Yunweiling volatile oil on gastrin (GAS) and motilin (MTL)

[0110] from Figure 2 It can be seen that after modeling, the levels of GAS and MTL in the blood of mice were significantly reduced. P <0.0.1), after drug treatment, the levels of GAS and MTL in the blood significantly increased, and the small intestinal propulsion rate increased with increasing dose, which was statistically significant compared with the model group. P <0.01). This indicates that the Yunweiling volatile oil prepared in Example 1 has the function of promoting the secretion of GAS and MTL.

[0111] 3. Comparison of rat body weight, food intake, and food utilization rate

[0112] The results are shown in Table 1. Compared with the normal group, the food intake of rats in the medium and high dose groups of Yunweiling volatile oil was significantly increased. P Although there was no significant difference in the low-dose group of Yunweiling volatile oil (<0.0001), it still increased food intake, and the high-dose group was better than the positive group. This indicates that it has the function of promoting appetite.

[0113] Table 1. Effects of Yunweiling volatile oil on body weight, body weight gain, food intake, and food utilization rate in rats.

[0114]

[0115] Note: 1) indicates comparison with the normal group. P <0.05;2) indicates a comparison with the normal group. P <0.01;3) indicates a comparison with the normal group. P <0.001;4) indicates a comparison with the normal group. P <0.0001.

[0116] 4. Comparison of pepsin activity and pepsin excretion in rats

[0117] from Figure 3 It can be seen that, compared with the normal group of rats, the pepsin activity of rats in each group of Yunweiling volatile oil was significantly increased. P<0.0001), and all were better than the positive drug group. The pepsin excretion of rats in each group of Yunweiling volatile oil was significantly increased ( P <0.05), indicating that Yunweiling volatile oil has the functions of enhancing pepsin activity and promoting pepsin secretion.

[0118] Experimental Example 2 Detection of the function of promoting digestion and increasing appetite of the traditional Chinese medicine composition of the present invention

[0119] I. Experimental method

[0120] 1. Experimental animals: SPF-grade KM male mice, body weight 18 - 22 g, 6 weeks old; SPF-grade SD male rats, body weight 120 - 150 g, 8 weeks old; all were purchased from Spey Foster (Beijing Biotechnology Co., Ltd.), production license number SCXK (Beijing) 2019 - 0010, and raised in an SPF-grade environment, with the indoor temperature of 22 - 25 °C.

[0121] 2. Drugs and reagents: Jianwei Xiaoshi tablets, batch number 22072065, Jiangzhong Pharmaceutical Co., Ltd.; Loperamide Hydrochloride Capsules, batch number LHJ5501, Janssen Pharmaceutical Co., Ltd.; activated carbon, Aladdin Reagent (Shanghai) Co., Ltd.; Loperamide Hydrochloride: 2.5 mg / kg;

[0122] 3. Modeling, grouping and drug administration

[0123] Preparation of the modeling agent: Take Loperamide Hydrochloride Capsules, remove the capsule shells, dissolve the powder with 0.5% CMC-Na, and prepare a suspension with a concentration of 2.5 mg / kg. On the experimental end day, the model group, the positive control group of Jianwei Xiaoshi tablets, and each drug administration group were given the modeling agent, and the administration volume was 10 ml / kg.

[0124] Preparation of carbon powder indicator: Take 10 g of gum arabic, add 80 mL of water, and boil until transparent. Add 5 g of carbon powder to the above solution and boil it 3 times. After cooling, make up the volume to 100 mL to obtain the carbon powder indicator

[0125] Forty SPF-grade male KM mice were randomly divided into 5 groups (n = 8) according to body weight after 3 - 5 days of adaptive feeding, namely the normal group, the model group, the positive control group of Jianwei Xiaoshi tablets (940 mg / kg), the traditional Chinese medicine composition group of Example 5, and the traditional Chinese medicine composition group of Comparative Example 1. The administration concentration was 1.74 g / kg, and the administration volume was 10 mL / kg. After continuous drug administration for 15 days, the small intestine propulsion function of the mice was measured.

[0126] Thirty-six SPF-grade male SD rats were acclimatized for 3-5 days and then randomly divided into four groups (n = 6) according to body weight: a normal group, a positive control group (1.33 g / kg) of digestive tablets, a group using the herbal composition from Example 5, and a group using the herbal composition from Comparative Example 1. The dosage for all groups was 1.2 g / kg, and the administration volume was 10 mL / kg. The rats were administered the medication continuously for 30 days. Food intake was recorded at 9:00 AM, and body weight was measured twice a week. At the end of the experiment, body weight was recorded, and the weight gain, food utilization rate, total food intake, and pepsin digestive enzyme levels were calculated.

[0127] 4. Observation indicators:

[0128] 4.1 Determination of small intestinal propulsion rate

[0129] Before the end of the experiment, mice were fasted for 16 hours but allowed free access to water. On the last day of the experiment, the normal group and the model group were administered 0.5% CMC-Na solution by gavage, while the drug administration groups were administered the corresponding drugs by gavage. 30 minutes later, the normal group was administered 0.5% CMC-Na solution by gavage, while the model group, positive control group, and drug administration groups were administered the modeling agent by gavage. 30 minutes later, each group was administered carbon indicator by gavage. 25 minutes later, the mice were sacrificed, the abdominal cavity was opened, the mesentery was separated, and the small intestine from the upper end of the pylorus to the ileocecal junction was taken. The small intestine was straightened and placed on white paper, and the total length of the small intestine and the distance from the pylorus to the carbon indicator were measured. The carbon propulsion rate and the carbon propulsion rate conversion value of the small intestine were calculated.

[0130]

[0131]

[0132] Note: P - Small intestinal carbon propulsion rate

[0133] 4.2 Determination of rat body weight, body weight gain, food intake, and food utilization rate

[0134] After 30 days of gavage administration to rats, the weight gain, food intake, and food utilization rate were calculated.

[0135]

[0136] 4.3 Determination of pepsin and pepsin excretion in rats

[0137] Rats were fasted for 24 hours before the end of the experiment, but allowed free access to water. On the last day of the experiment, rats were anesthetized with sodium pentobarbital, and the pylorus was ligated for 2 hours. Gastric fluid was collected and its volume was measured. 15 mL of 0.05 mol / L HCl solution was added to each mL of collected gastric fluid and mixed in a centrifuge tube. Two freshly prepared protein tubes were added, sealed, and incubated at 37 ℃ for 24 hours. The tubes were then removed, and the length (mm) of the transparent portion at both ends of each protein tube was measured using calipers. The average value of the four ends was calculated, and pepsin activity units were calculated using the formula for pepsin activity units.

[0138] active.

[0139] Pepsin activity units (U / mL) = (mean length of the transparent portion of the four-end protein tube) × 16

[0140] Pepsin excretion (U / h) = Pepsin activity × Gastric juice volume per hour

[0141] 5. Data Statistics and Analysis

[0142] All experimental data are expressed as averages. Standard deviation ( S) indicates that the data was statistically processed and analyzed using data software, and comparisons between the two groups were performed using... t For comparisons among multiple groups, one-way ANOVA was used to test the variance. P <0.05 is considered statistically significant.

[0143] II. Results Analysis

[0144] 1. Effects of small intestinal propulsion rate and small intestinal propulsion rate conversion value in mice

[0145] from Figure 1 It can be seen that after modeling, the small intestinal propulsion rate and small intestinal propulsion conversion value of the mice were significantly reduced. P <0.0.1), after treatment, the small intestinal propulsion rate and small intestinal transition value of mice in Example 5 group were significantly improved, which were superior to those of Comparative Example 1 group and the positive drug group, and were statistically significant compared with the model group. P <0.01).

[0146] 2. Comparison of rat body weight, food intake, and food utilization rate

[0147] The results are shown in Table 1. Compared with the normal group, the food intake of rats in Example 5 and Comparative Example 1 was significantly increased. P <0.0001), and the effect of Example 5 is better than that of Comparative Example 1, indicating that the traditional Chinese medicine composition provided by the present invention has the function of promoting appetite.

[0148] Table 1 Comparison of the effects of the traditional Chinese medicine composition of Example 5 and Comparative Example 1 on rat body weight, food intake, and food utilization rate.

[0149]

[0150] Note: Compared with the normal group: * P <0.05 ** P <0.01 *** P <0.001 **** P <0.0001

[0151] 3. Comparison of pepsin activity and pepsin excretion in rats

[0152] from Figure 2 It can be seen that, compared with the normal group of rats, the pepsin activity and excretion of rats in Example 5 and Comparative Example 1 were significantly increased. P <0.0001), and the effect of Example 5 is significantly better than that of Comparative Example 1 and the positive drug group. This indicates that the traditional Chinese medicine composition provided by the present invention has the function of enhancing pepsin activity and promoting pepsin secretion, wherein Yunweiling volatile oil can significantly enhance the above-mentioned activities of the traditional Chinese medicine composition.

Claims

1. A formulation of a digestive aid and appetite stimulating traditional Chinese medicine composition based on Yunweiling volatile oil, characterized in that, The ingredients, by weight, consist of 10-20 parts Yunweiling, 10-20 parts Poria cocos, 5-15 parts dried tangerine peel, 5-15 parts roasted hawthorn, 5-15 parts roasted malt, and 5-10 parts Amomum villosum; the method for preparing the decoction is as follows: 1) Take Yunweiling powder, add 8-10 times the weight of water and reflux at 90℃-100℃ for 3-5 hours. Collect the volatile oil with a volatile oil extractor, add anhydrous sodium sulfate to dehydrate and centrifuge and filter to obtain Yunweiling volatile oil. The refluxed Yunweiling residue and the refluxed Yunweiling aqueous solution are for later use. 2) Mix Poria cocos, dried tangerine peel, charred hawthorn, stir-fried malt, and Amomum villosum with the Yunweiling medicine residue after distillation in step 1), add 6-8 times the amount of water and decoct for 20-40 minutes. Add 4-8 times the amount of water to the decocted medicine residue and decoct for 20-40 minutes. Mix the two decoctions together. 3) Mix the aqueous solution of Yunweiling in step 1) with the decoction obtained in step 2), then add the volatile oil of Yunweiling obtained in step 1), mix thoroughly, and the decoction is obtained.

2. A formulation of a digestive aid and appetite stimulating traditional Chinese medicine composition based on Yunweiling volatile oil, characterized in that, The raw materials, by weight, consist of 10-20 parts Yunweiling, 10-20 parts Poria cocos, 5-15 parts dried tangerine peel, 5-15 parts roasted hawthorn, 5-15 parts roasted malt, and 5-10 parts Amomum villosum; the method for preparing the pills is as follows: 1) Take Yunweiling powder, add 8-10 times the weight of water and reflux at 90℃-100℃ for 3-5 hours. Collect the volatile oil with a volatile oil extractor, add anhydrous sodium sulfate to dehydrate and centrifuge and filter to obtain Yunweiling volatile oil. The refluxed Yunweiling residue and the refluxed Yunweiling aqueous solution are for later use. 2) Mix Poria cocos, dried tangerine peel, charred hawthorn, stir-fried malt, and Amomum villosum with the Yunweiling medicine residue after distillation in step 1), add 6-8 times the amount of water and decoct for 20-40 minutes. Add 4-8 times the amount of water to the decocted medicine residue and decoct for 20-40 minutes. Mix the two decoctions together. 3) Mix the aqueous solution of Yunweiling in step 1) with the decoction obtained in step 2), concentrate it into an extract of 1.5~2g / mL, then add the volatile oil of Yunweiling obtained in step 1), add an appropriate amount of excipients, mix thoroughly, and then use water to form pills to obtain pills.

3. A formulation of a digestive aid and appetite stimulating traditional Chinese medicine composition based on Yunweiling volatile oil, characterized in that, The raw materials, by weight, consist of 10-20 parts Yunweiling, 10-20 parts Poria cocos, 5-15 parts dried tangerine peel, 5-15 parts roasted hawthorn, 5-15 parts roasted malt, and 5-10 parts Amomum villosum; the method for preparing granules is as follows: 1) Take Yunweiling powder, add 8-10 times the weight of water and reflux at 90℃-100℃ for 3-5 hours. Collect the volatile oil with a volatile oil extractor, add anhydrous sodium sulfate to dehydrate and centrifuge and filter to obtain Yunweiling volatile oil. The refluxed Yunweiling residue and the refluxed Yunweiling aqueous solution are for later use. 2) Weigh 10-20g of β-cyclodextrin into a 50mL beaker, add 10-25mL of anhydrous ethanol and stir to dissolve at 45-65℃. Then add the Yunweiling volatile oil obtained in step 1) dropwise, keep at 45-65℃ and stir at 300-900r / min for 1.5-2.5h, concentrate and dry under reduced pressure at 40℃, wash 3 times with petroleum ether, and evaporate to constant mass at room temperature to obtain the Yunweiling volatile oil inclusion complex. 3) Mix Poria cocos, dried tangerine peel, roasted hawthorn, stir-fried malt, and Amomum villosum with the Yunweiling medicine residue after distillation in step 1), add 6-8 times the amount of water and decoct for 20-40 minutes. Add 4-8 times the amount of water to the decocted medicine residue and decoct for 20-40 minutes. Mix the two decoctions together. 4) Mix the Yunweiling aqueous solution from step 1) with the decoction obtained in step 3), concentrate and dry into powder, then add the Yunweiling volatile oil inclusion complex obtained in step 2), mix thoroughly and pass through a 100-mesh sieve to obtain a mixture, add an appropriate amount of 70%~90% ethanol for wet granulation, and dry to obtain granules.

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