WO2020187018A1 - Traditional chinese medicine composition for loosening bowels to relieve constipation, preparation method therefor and use thereof - Google Patents

Traditional chinese medicine composition for loosening bowels to relieve constipation, preparation method therefor and use thereof Download PDF

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Publication number
WO2020187018A1
WO2020187018A1 PCT/CN2020/077630 CN2020077630W WO2020187018A1 WO 2020187018 A1 WO2020187018 A1 WO 2020187018A1 CN 2020077630 W CN2020077630 W CN 2020077630W WO 2020187018 A1 WO2020187018 A1 WO 2020187018A1
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chinese medicine
medicine composition
traditional chinese
extraction
extract
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PCT/CN2020/077630
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French (fr)
Chinese (zh)
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杜成强
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清华德人西安幸福制药有限公司
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • A61K36/8968—Ophiopogon (Lilyturf)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/10—Laxatives

Definitions

  • the present invention relates to the technical field of traditional Chinese medicine, in particular to a traditional Chinese medicine composition for moisturizing the intestines and laxative, its preparation method and application.
  • Constipation is a common clinical symptom, which mainly refers to a decrease in the frequency of bowel movements, a decrease in stool volume, dry stool, and laborious defecation. When two or more of the above symptoms are present, it can be diagnosed as symptomatic constipation. It is usually based on the reduction of defecation frequency, generally defecation once every 2 to 3 days or longer (or ⁇ 3 times a week) is constipation.
  • the present invention aims to provide a traditional Chinese medicine composition for moisturizing the bowel and laxative, its preparation method and application, so as to reduce the risk of side effects after taking the medicine.
  • a Chinese medicinal composition for moisturizing the bowel and laxative is provided.
  • the active ingredient of the traditional Chinese medicine composition is made from the extract of the raw material medicine, and the raw material medicine is composed of aloe and Ophiopogon japonicus with a mass ratio of 2-5:1.5-12.
  • the raw material medicine is composed of aloe and Ophiopogon japonicus with a mass ratio of 5:9.
  • the traditional Chinese medicine composition also includes pharmaceutically acceptable excipients.
  • the dosage forms of the Chinese medicine composition are tablets, granules, capsules, pills, suppositories, powders, ointments, drops, aerosols, powder mists, solutions, suspensions, syrups, mixtures, wines Medicine, tea, lozenge, freeze-dried powder injection, or emulsion.
  • the traditional Chinese medicine composition is prepared by the following steps: S1, taking aloe and Ophiopogon japonicus with a mass ratio of 2-5:1.5-12 in an extraction tank for water extraction, and the vapor pressure of extraction is 0.25-0.35 MPa , The temperature is 70 ⁇ 90°C, the extract is obtained after the extraction is completed; S2, the extract is concentrated under reduced pressure, the vacuum degree of the reduced pressure concentration is -0.08 ⁇ -0.06MPa, the vapor pressure is 0.25 ⁇ 0.35MPa, The temperature is 60-70°C to obtain a clear ointment; and S3, the clear ointment is used as an active ingredient to prepare a traditional Chinese medicine composition for moisturizing and laxative.
  • the extraction is carried out in 2 or more times.
  • the leaching includes: adding 6-10 times the amount of water for the first time, leaching for 4 hours; and the second time 4-8 times the amount of water, leaching for 3 hours; the first leaching obtained from the first leaching
  • the extract and the second extract obtained from the second extraction are combined and filtered to obtain the extract.
  • S3 also includes drying and pulverizing the clear ointment to obtain a dry ointment powder, and then using the dry ointment powder as an effective ingredient to prepare a laxative Chinese medicine composition.
  • a method for preparing the above-mentioned traditional Chinese medicine composition includes the following steps: S1, taking aloe and Ophiopogon japonicus with a mass ratio of 2 to 5: 1.5 to 12 and placing them in an extraction tank for water extraction.
  • the vapor pressure of the extraction is 0.25 ⁇ 0.35 MPa, and the temperature is 70 ⁇
  • the extract is obtained after the extraction is completed;
  • the extract is concentrated under reduced pressure, the vacuum degree of the reduced pressure concentration is -0.08 ⁇ -0.06MPa, the vapor pressure is 0.25 ⁇ 0.35MPa, and the temperature is 60 ⁇ 70 °C to obtain a clear ointment;
  • the clear ointment is used as an active ingredient to prepare a laxative Chinese medicine composition;
  • the extraction is carried out in 2 or more times; more preferably, the extraction includes: the first time Add 6-10 times the amount of water and extract for 4 hours; and for the second time 4-8 times the amount of water, extract for 3 hours; combine the first extract obtained from the first extraction with the second extract The second extract is combined and filtered to obtain the extract; further preferably, S3 also includes drying and pulverizing the clear ointment to obtain a dry ointment powder, which is then used as an active ingredient to
  • the composition of the traditional Chinese medicine composition for moisturizing and laxative bowel movement is simple, and the active ingredients are extracted from aloe vera and Ophiopogon japonicus, avoiding excessive reactions between the components of complex components, and significantly reducing medication There is a risk of side effects afterwards, and it has a good laxative effect.
  • a traditional Chinese medicine composition for moisturizing the intestines and laxative is provided.
  • the active ingredients of the Chinese medicine composition are made of extracts of raw materials, and the mass ratio of the raw materials is 2-5: 1.5-12.
  • Composition of aloe and Ophiopogon japonicus is provided.
  • the composition of the traditional Chinese medicine composition for moisturizing and laxative bowel movement is simple, and the active ingredients are extracted from aloe vera and Ophiopogon japonicus, avoiding excessive reactions between the components of complex components, and significantly reducing medication There is a risk of side effects afterwards, and it has a good laxative effect.
  • the raw material medicine is composed of aloe and Ophiopogon japonicus with a mass ratio of 5:9.
  • the traditional Chinese medicine composition further includes pharmaceutically acceptable auxiliary materials.
  • the dosage form of the traditional Chinese medicine composition is tablet, granule, capsule, pill, suppository, powder, ointment, drops, aerosol Medicine, powder mist, solution, suspension, syrup, mixture, wine, tea, lozenge, lyophilized powder injection, or emulsion. It can be ordinary formulations, sustained-release formulations, controlled-release formulations, and various particle delivery systems.
  • the pharmaceutical carrier familiar to those skilled in the art can be used to prepare the traditional Chinese medicine pharmaceutical composition of the present invention containing an effective dose.
  • oral preparations such as tablets, capsules, solutions or suspensions
  • injectable preparations such as injectable solutions or suspensions, or injectable dry powders. Add water for injection immediately before injection use).
  • the carrier in the pharmaceutical composition includes: binders used in oral preparations (such as starch, usually corn, wheat or rice starch, gelatin, methylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidone), diluents (Such as lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, and/or glycerin), lubricants (such as silicon dioxide, talc, stearic acid or its salts, usually magnesium stearate or hard Calcium fatty acid, and/or polyethylene glycol), and if necessary, also containing disintegrating agents, such as starch, agar, alginic acid or its salts, usually sodium alginate, and/or effervescent mixtures, co-solvents, Stabilizers, suspending agents, non-coloring, flavoring agents, etc., preservatives, solubilizers, stabilizers, etc.
  • binders used in oral preparations such as starch
  • compositions can be administered orally or parenterally (for example, intravenously, subcutaneously, intraperitoneally or topically). If certain drugs are unstable under gastric conditions, they can be formulated into enteric-coated tablets.
  • the phrase "effective dose" of the Chinese medicine pharmaceutical composition of the present invention refers to a compound in a sufficient amount to treat a disorder with a reasonable effect/risk ratio suitable for any medical treatment and/or prevention.
  • the total daily dosage of the traditional Chinese medicine composition of the present invention must be determined by the attending physician within the scope of reliable medical judgment.
  • the specific therapeutically effective dose level must be determined based on a variety of factors, including the disorder being treated and the severity of the disorder; the activity of the specific compound used; the specific composition used; The age, weight, general health, gender, and diet of the patient; the time of administration, route of administration and excretion rate of the specific compound used; duration of treatment; drugs used in combination or concurrently with the specific compound used; and Similar factors well known in the medical field.
  • the practice in the art is that the dosage of the traditional Chinese medicine composition starts from a level lower than the level required to obtain the desired therapeutic effect, and gradually increases the dosage until the desired effect is obtained.
  • the dosage of the traditional Chinese medicine composition of the present invention for mammals, especially humans can range from 42 to 128 mg/kg ⁇ day (60 kg for adults).
  • the traditional Chinese medicine composition is prepared by the following steps: S1, taking aloe vera and Ophiopogon japonicus with a mass ratio of 2-5:1.5-12 in an extraction tank for water extraction.
  • the vapor pressure is 0.25 ⁇ 0.35MPa, the temperature is 70 ⁇ 90°C, the leaching liquid is obtained after the extraction is completed; S2, the leaching liquid is concentrated under reduced pressure, and the vacuum degree of the vacuum concentration is -0.08 ⁇ -0.06MPa.
  • the pressure is 0.25-0.35 MPa and the temperature is 60-70°C to obtain a clear ointment; and S3, the clear ointment is used as an active ingredient to prepare a laxative Chinese medicine composition.
  • the extraction is carried out in two or more times. More preferably, the leaching includes: adding 6-10 times the amount of water for the first time, leaching for 4 hours; and the second time 4-8 times the amount of water, leaching for 3 hours; The extract and the second extract obtained from the second extraction are combined and filtered to obtain the extract.
  • S3 further includes drying and pulverizing the clear ointment to obtain a dry ointment powder, and then using the dry ointment powder as an active ingredient to prepare a laxative Chinese medicine composition. This is more convenient for the storage and industrial production of effective ingredients.
  • a method for preparing the above-mentioned traditional Chinese medicine composition includes the following steps: S1, taking aloe and Ophiopogon japonicus with a mass ratio of 2 to 5: 1.5 to 12 and placing them in an extraction tank for water extraction.
  • the vapor pressure of the extraction is 0.25 ⁇ 0.35 MPa, and the temperature is 70 ⁇
  • the extract is obtained after the extraction is completed;
  • the extract is concentrated under reduced pressure, the vacuum degree of the reduced pressure concentration is -0.08 ⁇ -0.06MPa, the vapor pressure is 0.25 ⁇ 0.35MPa, and the temperature is 60 ⁇ 70 °C to obtain a clear ointment;
  • the clear ointment is used as an active ingredient to prepare a laxative Chinese medicine composition;
  • the extraction is carried out in 2 or more times; more preferably, the extraction includes: the first time Add 6-10 times the amount of water and extract for 4 hours; and for the second time 4-8 times the amount of water, extract for 3 hours; combine the first extract obtained from the first extraction with the second extract The second extract is combined and filtered to obtain the extract; further preferably, S3 also includes drying and pulverizing the clear ointment to obtain a dry ointment powder, which is then used as an active ingredient to
  • the compound diphenoxylate was given by oral gavage to establish a mouse small intestinal peristalsis inhibition model, calculate the ink advance rate of the small intestine within a certain period of time, and judge the gastrointestinal peristalsis function of the model mice.
  • Sample #1 Provided by Tsinghua Deren Xi’an Xingfu Pharmaceutical Co., Ltd. (Aloe-Ophiopogon japonicus is fed at 5:9, decocted and extracted with a proper amount of water, and concentrated to 500ml, which is called the original solution).
  • the crude drug amount is 0.4844g.
  • the medium dose is 2.40ml/20ml/kg, take 2.40ml stock solution and add distilled water to 20ml.
  • mice The administration volume of mice is 20ml/kg, once a day.
  • Compound diphenoxylate tablets each containing 2.5mg compound diphenoxylate tablets, take 25mg (10 tablets) of compound diphenoxylate tablets, grind with a mortar to form a powder, add water to 100ml, and prepare before use.
  • mice 60 Kunming male mice weighing 18-22 g were purchased from the Experimental Animal Center of Xi'an Jiaotong University.
  • mice According to the weight of the mice, they were randomly divided into blank control group, model control group, and 1# sample small, medium and high-dose groups, a total of 5 groups, each with 12 mice.
  • the blank control group and the model control group were given distilled water by gavage, and the test sample was given in the same way.
  • the administration volume was 20ml/Kg, once a day for 10 consecutive days.
  • mice After the mice were given gastric administration for 10 days, the mice in each group were fasted without water for 16 hours.
  • the model control group and each dose group of the sample were given compound diphenoxylate (5mg/kg BW) by gavage, and the blank control group was given distilled water.
  • the dose groups were given the ink containing the corresponding test sample (containing 5% activated carbon powder, 10% gum arabic) by intragastric administration, and the blank and model control groups were given ink.
  • the animal was killed by removing the cervical vertebrae immediately, opening the abdominal cavity to separate the mesentery, cutting the upper end of the intestine from the pylorus, lower end to the ileocecal, and placing it on the tray, gently pulling the small intestine into a straight line, and measuring the length of the intestine as "total length of small intestine" , From the pylorus to the ink preface is "the length of ink advancing".
  • the data can be counted using the analysis of variance and the pairwise comparison of the means of multiple experimental groups and a control group. See Table 1 below for details.
  • the ink advancing rate of the model control group was extremely statistically significant (P ⁇ 0.01), indicating that the model preparation was established.
  • the ink advancing rate of sample 1# in each dose group increased, and the ink advancing rate of the medium-dose group and the high-dose group had significant statistical significance (P ⁇ 0.05).
  • the modeling drug compound diphenoxylate was administered orally orally to establish a mouse model of constipation, and the time to the first black stool, the number of black stools and the weight of black stool discharged in 6 hours were measured, and the model mice were reflected Your bowel movements.
  • Sample #1 Provided by Tsinghua Deren Xi'an Fortune Pharmaceutical Co., Ltd. (Aloe-Ophiopogon is fed at 5:9, decocted and extracted with an appropriate amount of water, and concentrated to 500ml). Each 1ml is equivalent to 0.4844g of total crude drug.
  • the medium dose is 2.40ml/20ml/kg, take 2.40ml stock solution and add distilled water to 20ml.
  • mice The administration volume of mice is 20ml/kg, once a day.
  • Compound diphenoxylate tablets each containing 2.5mg compound diphenoxylate tablets, take 50mg (20 tablets) of compound diphenoxylate tablets, grind in a mortar and add distilled water to 100ml, and prepare before use.
  • mice 60 Kunming male mice weighing 18-22 g were purchased from the Experimental Animal Center of Xi'an Jiaotong University.
  • mice According to the weight of the mice, they were randomly divided into blank control group, model control group, and 1# sample small, medium, and high-dose groups, a total of 5 groups, each with 12 mice.
  • the blank control group and the model control group were given distilled water by gavage, and the test sample was given in the same way.
  • the administration volume was 20ml/Kg, once a day for 10 consecutive days.
  • mice After the mice were given gastric administration for 10 days, the mice in each group were fasted without water for 16 hours.
  • the model control group and 1# sample each dose group were given compound diphenoxylate (5mg/kg BW) by gavage, and the blank control group was given distilled water.
  • mice in the negative control group and the model control group were gavaged with ink, and the dose group was given the ink containing the test sample.
  • the animals were raised in single cages and drank and ate normally.
  • the data can be counted by the analysis of variance and the pairwise comparison of the means of multiple experimental groups and a control group. See Table 2, Table 3, and Table 4 for details.
  • the model control group's first black stool time has extremely significant statistical significance (P ⁇ 0.01), indicating that the model preparation is established.
  • P ⁇ 0.01 the time of first defecation in each dose group of 1# sample was shortened, but there was no statistical significance.
  • the test result can be determined as positive.
  • the 1# sample has significant statistical significance on intestinal peristalsis and defecation in mice (P ⁇ 0.05).
  • mice The model drug compound diphenoxylate was given by oral gavage to establish a mouse small intestinal peristalsis inhibition model, calculate the ink advancement rate of the small intestine within a certain period of time, and judge the gastrointestinal peristalsis function of the model mice.
  • mice defecation experiment The model drug compound diphenoxylate was given by oral gavage to establish a mouse model of constipation, and the time of the first defecation of the mice, the number of black defecation and black defecation within 6 hours were measured The weight reflects the defecation of the model mice.
  • Proportion I sample aloe-Ophiopogon japonicus was fed at a ratio of 3:1, and an appropriate amount of water was added to decocting to extract, and then concentrated to 500ml, which was called the original liquid I. Each 1ml is equivalent to 0.4844g of the total crude drug.
  • Proportion II sample Aloe-Ophiopogon japonicus is fed at a ratio of 5:9, decocted and extracted with an appropriate amount of water, and concentrated to 500 ml, which is called the original liquid II. Each 1ml is equivalent to 0.4844g of the total crude drug.
  • Proportion III sample Aloe-Ophiopogon japonicus is fed at a ratio of 1:6, decocted and extracted with an appropriate amount of water, and concentrated to 500ml, which is called the original solution III. Each 1ml is equivalent to 0.4844g of the total crude drug.
  • the original solution I, the original solution II, and the original solution III are prepared according to the small, medium and large doses respectively.
  • the method is as follows:
  • mice The administration volume of mice is 20ml/kg, once a day.
  • compound diphenoxylate solution take 10 compound diphenoxylate tablets (each tablet contains 2.5mg compound diphenoxylate), grind in a mortar and add distilled water to 100ml, and prepare before use.
  • compound diphenoxylate solution take 20 compound diphenoxylate tablets (each tablet contains 2.5 mg compound diphenoxylate), grind with a mortar and add distilled water to 100ml, and prepare before use.
  • the blank control group and the model control group were given distilled water by gavage, and the test sample was given in the same way.
  • the administration volume was 20ml/Kg, once a day for 10 consecutive days.
  • mice After the mice were given gastric administration for 10 days, the mice in each group were fasted without water for 16 hours.
  • the model control group and each dose group of the sample were given 0.025% compound diphenoxylate solution (5mg/kg BW) by gavage, and the blank control group was given distilled water.
  • the dose groups were given the ink containing the corresponding test sample (containing 5% activated carbon powder, 10% gum arabic) by intragastric administration, and the blank and model control groups were given ink.
  • the animal was killed by removing the cervical vertebrae immediately, opening the abdominal cavity to separate the mesentery, cutting the upper end of the intestine from the pylorus, lower end to the ileocecal, and placing it on the tray, gently pulling the small intestine into a straight line, and measuring the length of the intestine as "total length of small intestine" , From the pylorus to the ink preface is "the length of ink advancing".
  • the data was calculated by analysis of variance, a pairwise comparison method of the means of multiple experimental groups and a control group. See Table 5 below for details.
  • the ink advancing rate of the model control group was extremely statistically significant (P ⁇ 0.01), indicating that the model preparation was established.
  • the ink advancing rate of each dose group of the sample increased.
  • the proportion I sample medium and high dose group, the proportion II sample medium and high dose group, and the proportion III sample high dose group had significant statistical significance. (P ⁇ 0.05).
  • the blank control group and the model control group were given distilled water by gavage, and the test sample was given in the same way.
  • the administration volume was 20ml/Kg, once a day for 10 consecutive days.
  • mice After the mice were given gastric administration for 10 days, the mice in each group were fasted without water for 16 hours.
  • the model control group and each dose group of the samples were given 0.05% compound diphenoxylate solution (5mg/kg BW) by gavage, and the blank control group was given distilled water.
  • the data can be counted using the analysis of variance and the pairwise comparison of the means of multiple experimental groups and a control group. For details, see Table 6, Table 7 and Table 8.
  • the model control group's first black stool time has extremely significant statistical significance (P ⁇ 0.01), indicating that the model preparation is established.
  • P ⁇ 0.01 the proportion of samples I, II, and III samples in the middle-dose group and the high-dose group shortened the time of first defecation, but there was no statistical significance.
  • the test result can be determined as positive.
  • the ratio I (3:1), the ratio II (5:9), and the ratio III (1:6) all have a certain degree of laxative effect.
  • the intestinal laxative effect is ratio I (3:1)> ratio II (5:9)> ratio III (1:6).
  • the proportion of aloe should be appropriately reduced, so the ratio II (5:9) is the optimal ratio.
  • Aloe-Ophiopogon Chinese medicinal composition (sample 1 in Example 1), Aloe-Angelica-Ophiopogon japonicus-Fructus Aurantii Chinese medicinal composition (for the preparation method see patent: A Chinese medicinal composition for improving gastrointestinal function and Its preparation, patent number: ZL201110317780.9) It is confirmed by mouse functional experiments that the medium and large doses of each composition have the effect of moistening bowel and laxative. The daily intake of crude drugs in each group of mice (calculated as 20g) was calculated and calculated (see Table 9).
  • Aloe vera accounted for 35.7% in the aloe-Ophiopogon japonicus Chinese medicinal composition, and aloe vera accounted for 50.9% in the aloe-angelica-Ophiopogon japonicus-Fructus Aurantii Chinese medicinal composition. Reduce the risk of side effects after taking the medicine.

Abstract

Provided are a traditional Chinese medicine composition for loosening the bowels to relieve constipation, a preparation method therefor and the use thereof. The traditional Chinese medicine composition is prepared by extraction from aloe and Ophiopogonis radix with a mass ratio of 2-5 : 1.5-12.

Description

润肠通便的中药组合物、其制备方法及应用Traditional Chinese medicine composition for moistening bowel and laxative, its preparation method and application 技术领域Technical field
本发明涉及中药技术领域，具体而言，涉及一种润肠通便的中药组合物、其制备方法及应用。The present invention relates to the technical field of traditional Chinese medicine, in particular to a traditional Chinese medicine composition for moisturizing the intestines and laxative, its preparation method and application.
背景技术Background technique
便秘是临床常见症状，主要是指排便次数减少、粪便量减少、粪便干结、排便费力等。上述症状同时存在2种以上时，可诊断为症状性便秘。通常以排便频率减少为主，一般每2～3天或更长时间排便一次(或每周＜3次)即为便秘。Constipation is a common clinical symptom, which mainly refers to a decrease in the frequency of bowel movements, a decrease in stool volume, dry stool, and laborious defecation. When two or more of the above symptoms are present, it can be diagnosed as symptomatic constipation. It is usually based on the reduction of defecation frequency, generally defecation once every 2 to 3 days or longer (or <3 times a week) is constipation.
现代人的生活方式较前发生了很大的变化，不少人久坐不动，饮食测试食不厌精，摄入的纤维素越来越少，有的人过度饮酒，种种原因导致消化功能失常，大肠秘结是最常见的现象，给不少人带来难言之苦，影响了身体的健康。The lifestyle of modern people has undergone great changes compared with the past. Many people are sedentary, not tired of eating in diet tests, and consume less and less fiber. Some people drink excessively, and various reasons lead to digestive disorders. The secretion of the large intestine is the most common phenomenon, which brings unspeakable suffering to many people and affects the health of the body.
目前，市场上存在不少润肠通便的中药组合物，但是通常药物组分多，成分复杂，常言道“是药三分毒”，这在某种程度上增加了服药后产生副作用的风险。At present, there are many traditional Chinese medicine compositions for laxative and laxative in the market, but usually the medicine has many components and complex ingredients. As the saying goes, "the medicine is three parts poison", which increases the risk of side effects after taking the medicine to some extent. .
发明内容Summary of the invention
本发明旨在提供一种润肠通便的中药组合物、其制备方法及应用，以减低服药后产生副作用的风险。The present invention aims to provide a traditional Chinese medicine composition for moisturizing the bowel and laxative, its preparation method and application, so as to reduce the risk of side effects after taking the medicine.
为了实现上述目的，根据本发明的一个方面，提供了一种润肠通便的中药组合物。该中药组合物的有效成分由原料药的提取物制成，原料药由质量比为2～5：1.5～12的芦荟和麦冬组成。In order to achieve the above objective, according to one aspect of the present invention, a Chinese medicinal composition for moisturizing the bowel and laxative is provided. The active ingredient of the traditional Chinese medicine composition is made from the extract of the raw material medicine, and the raw material medicine is composed of aloe and Ophiopogon japonicus with a mass ratio of 2-5:1.5-12.
进一步地，原料药由质量比为5：9的芦荟和麦冬组成。Further, the raw material medicine is composed of aloe and Ophiopogon japonicus with a mass ratio of 5:9.
进一步地，中药组合物还包括药学上可接受的辅料。Further, the traditional Chinese medicine composition also includes pharmaceutically acceptable excipients.
进一步地，中药组合物的剂型为片剂、颗粒剂、胶囊剂、丸剂、栓剂、散剂、膏剂、滴剂、气雾剂、粉雾剂、溶液剂、混悬剂、糖浆剂、合剂、酒剂、茶剂、口含片、冻干粉针剂、或乳剂。Further, the dosage forms of the Chinese medicine composition are tablets, granules, capsules, pills, suppositories, powders, ointments, drops, aerosols, powder mists, solutions, suspensions, syrups, mixtures, wines Medicine, tea, lozenge, freeze-dried powder injection, or emulsion.
进一步地，中药组合物通过以下步骤制备得到：S1，取质量比为2～5：1.5～12的芦荟和麦冬置于提取罐中进行加水浸提，浸提的汽压为0.25～0.35MPa，温度为70～90℃，浸提完成后得到浸提液；S2，将浸提液进行减压浓缩，减压浓缩的真空度为-0.08～-0.06MPa，汽压为0.25～0.35MPa，温度为60～70℃，得到清膏；以及S3，将清膏作为有效成分制备成润肠通便的中 药组合物。Further, the traditional Chinese medicine composition is prepared by the following steps: S1, taking aloe and Ophiopogon japonicus with a mass ratio of 2-5:1.5-12 in an extraction tank for water extraction, and the vapor pressure of extraction is 0.25-0.35 MPa , The temperature is 70～90℃, the extract is obtained after the extraction is completed; S2, the extract is concentrated under reduced pressure, the vacuum degree of the reduced pressure concentration is -0.08～-0.06MPa, the vapor pressure is 0.25～0.35MPa, The temperature is 60-70°C to obtain a clear ointment; and S3, the clear ointment is used as an active ingredient to prepare a traditional Chinese medicine composition for moisturizing and laxative.
进一步地，浸提分2次或多次进行。Further, the extraction is carried out in 2 or more times.
进一步地，浸提包括：第一次加6～10倍量水，浸提4小时；以及第二次4～8倍量水，浸提3小时；将第一次浸提得到的第一浸提液与第二次浸提得到的第二浸提液合并过滤后得到浸提液。Furthermore, the leaching includes: adding 6-10 times the amount of water for the first time, leaching for 4 hours; and the second time 4-8 times the amount of water, leaching for 3 hours; the first leaching obtained from the first leaching The extract and the second extract obtained from the second extraction are combined and filtered to obtain the extract.
进一步地，S3还包括，将清膏干燥、粉碎，得干膏粉，然后将干膏粉作为有效成分制备成润肠通便的中药组合物。Further, S3 also includes drying and pulverizing the clear ointment to obtain a dry ointment powder, and then using the dry ointment powder as an effective ingredient to prepare a laxative Chinese medicine composition.
根据本发明的另一方面，提供了一种上述中药组合物的制备方法。该制备方法包括以下步骤：S1，取质量比为2～5：1.5～12的芦荟和麦冬置于提取罐中进行加水浸提，浸提的汽压为0.25～0.35MPa，温度为70～90℃，浸提完成后得到浸提液；S2，将浸提液进行减压浓缩，减压浓缩的真空度为-0.08～-0.06MPa，汽压为0.25～0.35MPa，温度为60～70℃，得到清膏；以及S3，将清膏作为有效成分制备成润肠通便的中药组合物；优选的，浸提分2次或多次进行；更优选的，浸提包括：第一次加6～10倍量水，浸提4小时；以及第二次4～8倍量水，浸提3小时；将第一次浸提得到的第一浸提液与第二次浸提得到的第二浸提液合并过滤后得到浸提液；进一步优选的，S3还包括，将清膏干燥、粉碎，得干膏粉，然后将作为有效成分制备成润肠通便的中药组合物。According to another aspect of the present invention, there is provided a method for preparing the above-mentioned traditional Chinese medicine composition. The preparation method includes the following steps: S1, taking aloe and Ophiopogon japonicus with a mass ratio of 2 to 5: 1.5 to 12 and placing them in an extraction tank for water extraction. The vapor pressure of the extraction is 0.25 ~ 0.35 MPa, and the temperature is 70 ~ At 90℃, the extract is obtained after the extraction is completed; S2, the extract is concentrated under reduced pressure, the vacuum degree of the reduced pressure concentration is -0.08～-0.06MPa, the vapor pressure is 0.25～0.35MPa, and the temperature is 60～70 °C to obtain a clear ointment; and S3, the clear ointment is used as an active ingredient to prepare a laxative Chinese medicine composition; preferably, the extraction is carried out in 2 or more times; more preferably, the extraction includes: the first time Add 6-10 times the amount of water and extract for 4 hours; and for the second time 4-8 times the amount of water, extract for 3 hours; combine the first extract obtained from the first extraction with the second extract The second extract is combined and filtered to obtain the extract; further preferably, S3 also includes drying and pulverizing the clear ointment to obtain a dry ointment powder, which is then used as an active ingredient to prepare a laxative Chinese medicine composition.
根据本发明的另一方面，提供了一种上述润肠通便的中药组合物在制备润肠通便的药物中的应用。According to another aspect of the present invention, there is provided an application of the above-mentioned Chinese medicine composition for moisturizing and laxative in preparing a medicine for moisturizing and laxative.
应用本发明的技术方案，润肠通便的中药组合物成分简单，有效成分从芦荟和麦冬中提取，避免了复杂成分之间组分之间可能存在的过多反应，明显的降低了服药后产生副作用的风险，并且具有良好的润肠通便效果。Using the technical solution of the present invention, the composition of the traditional Chinese medicine composition for moisturizing and laxative bowel movement is simple, and the active ingredients are extracted from aloe vera and Ophiopogon japonicus, avoiding excessive reactions between the components of complex components, and significantly reducing medication There is a risk of side effects afterwards, and it has a good laxative effect.
具体实施方式detailed description
需要说明的是，在不冲突的情况下，本申请中的实施例及实施例中的特征可以相互组合。下面将结合实施例来详细说明本发明。It should be noted that the embodiments in this application and the features in the embodiments can be combined with each other if there is no conflict. Hereinafter, the present invention will be described in detail in conjunction with embodiments.
现有市场上存在的润肠通便的中药组合物，但是通常药物组分多，成分复杂，这在某种程度上增加了服药后产生副作用的风险。为了降低这种风险，本发明的发明人对润肠通便的中药组合物进行了深入的研究。在研究过程中意外发现，仅仅芦荟和麦冬按照特定的比例进行配置作为原料药的提取物就能够达到良好的效果，这样就可以避免复杂成分之间组分之间可能存在的过多反应，明显的降低了服药后产生副作用的风险，可以说是取得了预料不到的效果。根据本发明一种典型的实施方式，提供一种润肠通便的中药组合物，中药组合物的有效成分由原料药的提取物制成，原料药由质量比为2～5：1.5～12的芦荟和麦冬组成。There are traditional Chinese medicine compositions for laxative and laxative in the market, but usually the medicine has many components and complex ingredients, which to some extent increases the risk of side effects after taking the medicine. In order to reduce this risk, the inventor of the present invention has conducted in-depth research on a traditional Chinese medicine composition for moisturizing and laxative. During the research, it was unexpectedly discovered that only aloe vera and Ophiopogon japonicus were prepared in a specific ratio as an extract of raw materials to achieve good results, so as to avoid excessive reactions between the components of complex ingredients. Significantly reduces the risk of side effects after taking the medicine, and it can be said that unexpected results have been achieved. According to a typical embodiment of the present invention, a traditional Chinese medicine composition for moisturizing the intestines and laxative is provided. The active ingredients of the Chinese medicine composition are made of extracts of raw materials, and the mass ratio of the raw materials is 2-5: 1.5-12. Composition of aloe and Ophiopogon japonicus.
应用本发明的技术方案，润肠通便的中药组合物成分简单，有效成分从芦荟和麦冬中提 取，避免了复杂成分之间组分之间可能存在的过多反应，明显的降低了服药后产生副作用的风险，并且具有良好的润肠通便效果。Using the technical solution of the present invention, the composition of the traditional Chinese medicine composition for moisturizing and laxative bowel movement is simple, and the active ingredients are extracted from aloe vera and Ophiopogon japonicus, avoiding excessive reactions between the components of complex components, and significantly reducing medication There is a risk of side effects afterwards, and it has a good laxative effect.
考虑到芦荟-麦冬组合物安全性问题，优选的，原料药由质量比为5：9的芦荟和麦冬组成。Considering the safety of the aloe-Ophiopogon japonicus composition, preferably, the raw material medicine is composed of aloe and Ophiopogon japonicus with a mass ratio of 5:9.
根据本发明一种典型的实施方式，中药组合物还包括药学上可接受的辅料，中药组合物的剂型为片剂、颗粒剂、胶囊剂、丸剂、栓剂、散剂、膏剂、滴剂、气雾剂、粉雾剂、溶液剂、混悬剂、糖浆剂、合剂、酒剂、茶剂、口含片、冻干粉针剂、或乳剂。可以是普通制剂、缓释制剂、控释制剂及各种微粒给药系统。According to a typical embodiment of the present invention, the traditional Chinese medicine composition further includes pharmaceutically acceptable auxiliary materials. The dosage form of the traditional Chinese medicine composition is tablet, granule, capsule, pill, suppository, powder, ointment, drops, aerosol Medicine, powder mist, solution, suspension, syrup, mixture, wine, tea, lozenge, lyophilized powder injection, or emulsion. It can be ordinary formulations, sustained-release formulations, controlled-release formulations, and various particle delivery systems.
运用本领域技术人员熟悉的药物载体可以制备成含有效剂量的本发明的中药药物组合物。例如，口服制剂(如片剂、胶囊剂、溶液或混悬液)；可注射的制剂(如可注射的溶液或混悬液，或者是可注射的干燥粉末，在注射前加入注射水可立即使用)。药物组合物中载体包括：口服制剂使用的粘合剂(如淀粉，通常是玉米、小麦或米淀粉、明胶、甲基纤维素、羧甲基纤维素钠和/或聚乙烯吡咯烷酮)，稀释剂(如乳糖、右旋糖、蔗糖、甘露醇、山梨醇、纤维素，和/或甘油)，润滑剂(如二氧化硅、滑石、硬脂酸或其盐，通常是硬脂酸镁或硬脂酸钙，和/或聚乙二醇)，以及如果需要，还含有崩解剂，如淀粉、琼脂、海藻酸或其盐，通常是藻酸钠，和/或泡腾混合物，助溶剂、稳定剂、悬浮剂、无色素、矫味剂等，可注射的制剂使用的防腐剂、加溶剂、稳定剂等；局部制剂用的基质、稀释剂、润滑剂、防腐剂等。药物制剂可以经口服或胃肠外方式(例如静脉内、皮下、腹膜内或局部)给药，如果某些药物在胃部条件下是不稳定的，可以将其配制成肠衣片剂。The pharmaceutical carrier familiar to those skilled in the art can be used to prepare the traditional Chinese medicine pharmaceutical composition of the present invention containing an effective dose. For example, oral preparations (such as tablets, capsules, solutions or suspensions); injectable preparations (such as injectable solutions or suspensions, or injectable dry powders). Add water for injection immediately before injection use). The carrier in the pharmaceutical composition includes: binders used in oral preparations (such as starch, usually corn, wheat or rice starch, gelatin, methylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidone), diluents (Such as lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, and/or glycerin), lubricants (such as silicon dioxide, talc, stearic acid or its salts, usually magnesium stearate or hard Calcium fatty acid, and/or polyethylene glycol), and if necessary, also containing disintegrating agents, such as starch, agar, alginic acid or its salts, usually sodium alginate, and/or effervescent mixtures, co-solvents, Stabilizers, suspending agents, non-coloring, flavoring agents, etc., preservatives, solubilizers, stabilizers, etc. for injectable preparations; bases, diluents, lubricants, preservatives, etc. for topical preparations. Pharmaceutical preparations can be administered orally or parenterally (for example, intravenously, subcutaneously, intraperitoneally or topically). If certain drugs are unstable under gastric conditions, they can be formulated into enteric-coated tablets.
词语“有效剂量”的本发明中药药物组合物指以适用于任何医学治疗和/或预防的合理效果/风险比治疗障碍的足够量的化合物。但应认识到，本发明的中药药物组合物的总日用量须由主诊医师在可靠的医学判断范围内作出决定。对于任何具体的患者，具体的治疗有效剂量水平须根据多种因素而定，所述因素包括所治疗的障碍和该障碍的严重程度；所采用的具体化合物的活性；所采用的具体组合物；患者的年龄、体重、一般健康状况、性别和饮食；所采用的具体化合物的给药时间、给药途径和排泄率；治疗持续时间；与所采用的具体化合物组合使用或同时使用的药物；及医疗领域公知的类似因素。例如，本领域的做法是，中药药物组合物的剂量从低于为得到所需治疗效果而要求的水平开始，逐渐增加剂量，直到得到所需的效果。一般说来，本发明中药药物组合物用于哺乳动物特别是人的剂量可以介于42～128mg/kg·天(成人以60kg计)。The phrase "effective dose" of the Chinese medicine pharmaceutical composition of the present invention refers to a compound in a sufficient amount to treat a disorder with a reasonable effect/risk ratio suitable for any medical treatment and/or prevention. However, it should be recognized that the total daily dosage of the traditional Chinese medicine composition of the present invention must be determined by the attending physician within the scope of reliable medical judgment. For any specific patient, the specific therapeutically effective dose level must be determined based on a variety of factors, including the disorder being treated and the severity of the disorder; the activity of the specific compound used; the specific composition used; The age, weight, general health, gender, and diet of the patient; the time of administration, route of administration and excretion rate of the specific compound used; duration of treatment; drugs used in combination or concurrently with the specific compound used; and Similar factors well known in the medical field. For example, the practice in the art is that the dosage of the traditional Chinese medicine composition starts from a level lower than the level required to obtain the desired therapeutic effect, and gradually increases the dosage until the desired effect is obtained. Generally speaking, the dosage of the traditional Chinese medicine composition of the present invention for mammals, especially humans, can range from 42 to 128 mg/kg·day (60 kg for adults).
根据本发明一种典型的实施方式，中药组合物通过以下步骤制备得到：S1，取质量比为2～5：1.5～12的芦荟和麦冬置于提取罐中进行加水浸提，浸提的汽压为0.25～0.35MPa，温度为70～90℃，浸提完成后得到浸提液；S2，将浸提液进行减压浓缩，减压浓缩的真空度为-0.08～-0.06MPa，汽压为0.25～0.35MPa，温度为60～70℃，得到清膏；以及S3，将清膏作为有效成分制备成润肠通便的中药组合物。According to a typical embodiment of the present invention, the traditional Chinese medicine composition is prepared by the following steps: S1, taking aloe vera and Ophiopogon japonicus with a mass ratio of 2-5:1.5-12 in an extraction tank for water extraction. The vapor pressure is 0.25～0.35MPa, the temperature is 70～90℃, the leaching liquid is obtained after the extraction is completed; S2, the leaching liquid is concentrated under reduced pressure, and the vacuum degree of the vacuum concentration is -0.08～-0.06MPa. The pressure is 0.25-0.35 MPa and the temperature is 60-70°C to obtain a clear ointment; and S3, the clear ointment is used as an active ingredient to prepare a laxative Chinese medicine composition.
尽管不能明确上述步骤所得清膏中的所有组分及其含量，但是发明人发现，通过上述步 骤值得的中药组合物具有较好的疗效，同时，因为原始原料成分简单，因为可能产生的副作用风险也得到了极大的降低。Although it is impossible to clarify all the components and their contents in the cleansing ointment obtained by the above steps, the inventor found that the traditional Chinese medicine composition worthy of the above steps has better curative effect. At the same time, because the original raw materials are simple, because of the possible side effects. It has also been greatly reduced.
为了使有效成分得到充分的浸提，优选的，浸提分2次或多次进行。更优选的，浸提包括：第一次加6～10倍量水，浸提4小时；以及第二次4～8倍量水，浸提3小时；将第一次浸提得到的第一浸提液与第二次浸提得到的第二浸提液合并过滤后得到浸提液。In order to obtain sufficient extraction of the active ingredients, it is preferable that the extraction is carried out in two or more times. More preferably, the leaching includes: adding 6-10 times the amount of water for the first time, leaching for 4 hours; and the second time 4-8 times the amount of water, leaching for 3 hours; The extract and the second extract obtained from the second extraction are combined and filtered to obtain the extract.
根据本发明一种典型的实施方式，S3还包括，将清膏干燥、粉碎，得干膏粉，然后将干膏粉作为有效成分制备成润肠通便的中药组合物。这样更方便有效成分的储存和工业化生产。According to a typical embodiment of the present invention, S3 further includes drying and pulverizing the clear ointment to obtain a dry ointment powder, and then using the dry ointment powder as an active ingredient to prepare a laxative Chinese medicine composition. This is more convenient for the storage and industrial production of effective ingredients.
根据本发明一种典型的实施方式，提供了一种上述中药组合物的制备方法。该制备方法包括以下步骤：S1，取质量比为2～5：1.5～12的芦荟和麦冬置于提取罐中进行加水浸提，浸提的汽压为0.25～0.35MPa，温度为70～90℃，浸提完成后得到浸提液；S2，将浸提液进行减压浓缩，减压浓缩的真空度为-0.08～-0.06MPa，汽压为0.25～0.35MPa，温度为60～70℃，得到清膏；以及S3，将清膏作为有效成分制备成润肠通便的中药组合物；优选的，浸提分2次或多次进行；更优选的，浸提包括：第一次加6～10倍量水，浸提4小时；以及第二次4～8倍量水，浸提3小时；将第一次浸提得到的第一浸提液与第二次浸提得到的第二浸提液合并过滤后得到浸提液；进一步优选的，S3还包括，将清膏干燥、粉碎，得干膏粉，然后将作为有效成分制备成润肠通便的中药组合物。According to a typical embodiment of the present invention, a method for preparing the above-mentioned traditional Chinese medicine composition is provided. The preparation method includes the following steps: S1, taking aloe and Ophiopogon japonicus with a mass ratio of 2 to 5: 1.5 to 12 and placing them in an extraction tank for water extraction. The vapor pressure of the extraction is 0.25 ~ 0.35 MPa, and the temperature is 70 ~ At 90℃, the extract is obtained after the extraction is completed; S2, the extract is concentrated under reduced pressure, the vacuum degree of the reduced pressure concentration is -0.08～-0.06MPa, the vapor pressure is 0.25～0.35MPa, and the temperature is 60～70 °C to obtain a clear ointment; and S3, the clear ointment is used as an active ingredient to prepare a laxative Chinese medicine composition; preferably, the extraction is carried out in 2 or more times; more preferably, the extraction includes: the first time Add 6-10 times the amount of water and extract for 4 hours; and for the second time 4-8 times the amount of water, extract for 3 hours; combine the first extract obtained from the first extraction with the second extract The second extract is combined and filtered to obtain the extract; further preferably, S3 also includes drying and pulverizing the clear ointment to obtain a dry ointment powder, which is then used as an active ingredient to prepare a laxative Chinese medicine composition.
尽管不能明确上述步骤所得清膏中的所有组分及其含量，但是发明人发现，通过上述步骤值得的中药组合物具有较好的疗效，同时，因为原始原料成分简单，因为可能产生的副作用风险也得到了极大的降低。Although it is impossible to clarify all the components and their contents in the cleansing ointment obtained by the above steps, the inventor found that the traditional Chinese medicine composition worthy of the above steps has better curative effect. At the same time, because the original raw materials are simple, because of the possible side effects. It has also been greatly reduced.
根据本发明一种典型的实施方式，提供了一种上述润肠通便的中药组合物在制备润肠通便的药物中的应用。According to a typical embodiment of the present invention, there is provided an application of the above-mentioned Chinese medicine composition for moisturizing and laxative in preparing a medicine for moisturizing and laxative.
下面将结合实施例进一步说明本发明的有益效果。In the following, the beneficial effects of the present invention will be further described in conjunction with embodiments.
实施例1Example 1
一、1#样品对小白鼠小肠蠕动的影响1. The effect of sample 1# on intestinal peristalsis in mice
1.原理1. Principle
经口灌胃给予造模药物复方地芬诺酯，建立小鼠小肠蠕动抑制模型，计算一定时间内小肠的墨汁推进率，判断模型小鼠胃肠蠕动功能。The compound diphenoxylate was given by oral gavage to establish a mouse small intestinal peristalsis inhibition model, calculate the ink advance rate of the small intestine within a certain period of time, and judge the gastrointestinal peristalsis function of the model mice.
2.样品和仪器2. Samples and instruments
2.1样品和仪器2.1 Samples and instruments
2.1.1 1#样品：由清华德人西安幸福制药有限公司提供(芦荟-麦冬以5:9投料，加适量水煎煮提取，浓缩至500ml，称之为原液)，每1ml相当于总生药量0.4844g。2.1.1 Sample #1: Provided by Tsinghua Deren Xi’an Xingfu Pharmaceutical Co., Ltd. (Aloe-Ophiopogon japonicus is fed at 5:9, decocted and extracted with a proper amount of water, and concentrated to 500ml, which is called the original solution). The crude drug amount is 0.4844g.
上述原液制备方法如下：The preparation method of the above-mentioned stock solution is as follows:
取芦荟、麦冬同时置多功能提取罐中，第1次加6～10倍量水，浸提4小时，第二次4～8倍量水，浸提3小时，汽压0.25～0.35MPa，温度80℃，滤过，合并滤液，减压浓缩，真空度为-0.06～-0.08MPa，汽压为0.25～0.35MPa，温度为60～70℃，浓缩至500ml，称之为原液。Take aloe vera and Ophiopogon japonicus at the same time and put them in a multifunctional extraction tank, add 6-10 times the amount of water for the first time, extract for 4 hours, and extract 4-8 times the amount of water for the second time, extract for 3 hours, vapor pressure 0.25～0.35MPa , Temperature 80℃, filter, combine the filtrate, concentrate under reduced pressure, vacuum degree is -0.06～-0.08MPa, vapor pressure is 0.25～0.35MPa, temperature is 60～70℃, and concentrated to 500ml, which is called original solution.
2.1.2仪器：手术剪、眼科镊、直尺、注射器、活性炭粉、阿拉伯树胶、复方地芬诺酯、量筒、蒸馏水、托盘、计时器。2.1.2 Instruments: surgical scissors, ophthalmic forceps, ruler, syringe, activated carbon powder, gum arabic, compound diphenoxylate, measuring cylinder, distilled water, tray, timer.
2.2试剂配制2.2 Reagent preparation
2.2.1 1#样品的配制2.2.1 Preparation of 1# sample
小剂量0.24ml/20ml/kg，取0.24ml原液加蒸馏水至20ml。Small dose 0.24ml/20ml/kg, take 0.24ml stock solution and add distilled water to 20ml.
中剂量2.40ml/20ml/kg，取2.40ml原液加蒸馏水至20ml。The medium dose is 2.40ml/20ml/kg, take 2.40ml stock solution and add distilled water to 20ml.
大剂量7.20ml/20ml/kg，取7.20ml原液加蒸馏水至20ml。Large dose of 7.20ml/20ml/kg, take 7.20ml stock solution and add distilled water to 20ml.
小鼠给药容积均为20ml/kg，每天1次。The administration volume of mice is 20ml/kg, once a day.
2.2.2墨汁的配制2.2.2 Preparation of ink
准确称取阿拉伯树胶50g，加水400ml，煮沸至溶液透明，称取活性炭(粉状)25g加至上述溶液中煮沸三次，待溶液凉后加水定容至500ml，于冰箱中4℃保存，用前摇匀。Accurately weigh 50g of gum arabic, add 400ml of water, and boil until the solution is transparent. Weigh 25g of activated carbon (powdered) and add to the above solution and boil three times. After the solution is cool, add water to make the volume up to 500ml and store in the refrigerator at 4°C before use. Shake well.
2.2.3浓度0.025％复方地芬诺酯的配制2.2.3 Preparation of 0.025% compound diphenoxylate
复方地芬诺酯片，每片含复方地芬诺酯2.5mg，取复方地芬诺酯片25mg(10片)，用研钵研碎呈粉末后加水至100ml，临用前配制。Compound diphenoxylate tablets, each containing 2.5mg compound diphenoxylate tablets, take 25mg (10 tablets) of compound diphenoxylate tablets, grind with a mortar to form a powder, add water to 100ml, and prepare before use.
3.实验方法3. Experimental method
3.1实验动物3.1 Experimental animals
昆明雄性小鼠60只，体重18～22g，购自西安交通大学实验动物中心。60 Kunming male mice weighing 18-22 g were purchased from the Experimental Animal Center of Xi'an Jiaotong University.
3.2实验步骤3.2 Experimental procedure
3.2.1实验动物分组及给药3.2.1 Grouping and administration of experimental animals
按小鼠体重随机分层分为空白对照组、模型对照组、1#样品小、中、大剂量组，共5组，每组12只。空白对照组和模型对照组灌胃给蒸馏水，同样途径给予受试样品，给药容积20ml/Kg，连续10天，每天1次。According to the weight of the mice, they were randomly divided into blank control group, model control group, and 1# sample small, medium and high-dose groups, a total of 5 groups, each with 12 mice. The blank control group and the model control group were given distilled water by gavage, and the test sample was given in the same way. The administration volume was 20ml/Kg, once a day for 10 consecutive days.
3.2.2模型的建立3.2.2 Model establishment
小鼠灌胃10天后，各组小鼠禁食不禁水16h。模型对照组和样品各剂量组灌胃给予复方 地芬诺酯(5mg/kg BW)，空白对照组给蒸馏水。After the mice were given gastric administration for 10 days, the mice in each group were fasted without water for 16 hours. The model control group and each dose group of the sample were given compound diphenoxylate (5mg/kg BW) by gavage, and the blank control group was given distilled water.
3.2.3指标测定的具体方法3.2.3 Specific methods for index determination
给复方地芬诺酯0.5小时后，剂量组分别灌胃给予含相应受试样品的墨汁(含5％的活性炭粉、10％阿拉伯树胶)，空白和模型对照组给墨汁。25分钟后立即脱颈椎处死动物，打开腹腔分离肠系膜，剪取上端自幽门、下端至回盲部的肠管，置于托盘上，轻轻将小肠拉成直线，测量肠管长度为“小肠总长度”，从幽门至墨汁前言为“墨汁推进长度”。按下算式计算墨汁推进率(％)：0.5 hours after the compound diphenoxylate was given, the dose groups were given the ink containing the corresponding test sample (containing 5% activated carbon powder, 10% gum arabic) by intragastric administration, and the blank and model control groups were given ink. After 25 minutes, the animal was killed by removing the cervical vertebrae immediately, opening the abdominal cavity to separate the mesentery, cutting the upper end of the intestine from the pylorus, lower end to the ileocecal, and placing it on the tray, gently pulling the small intestine into a straight line, and measuring the length of the intestine as "total length of small intestine" , From the pylorus to the ink preface is "the length of ink advancing". Calculate the ink advance rate (%) according to the following formula:
Figure PCTCN2020077630-appb-000001
Figure PCTCN2020077630-appb-000001
4.数据处理4. Data processing
数据可用方差分析，多个实验组和一个对照组均数的两两比较方法进行统计，详见下表1。The data can be counted using the analysis of variance and the pairwise comparison of the means of multiple experimental groups and a control group. See Table 1 below for details.
表1 1#样品对小鼠小肠蠕动的影响(
Figure PCTCN2020077630-appb-000002
n＝12) Table 1 The effect of 1# sample on mouse small intestine peristalsis (
Figure PCTCN2020077630-appb-000002
n=12)
Figure PCTCN2020077630-appb-000003
Figure PCTCN2020077630-appb-000003
注：与正常组比较 △P<0.01；与模型组比较 **P<0.01；与模型组比较 *P<0.05. Note: Compared with the normal group, △ P<0.01; compared with the model group ** P<0.01; compared with the model group * P<0.05.
5.实验结果5. Experimental results
与正常对照组比较，模型对照组墨汁推进率具有极显著统计学意义(P＜0.01)，说明模型制备成立。与模型对照组比较，1#样品各剂量组墨汁推进率增大，中剂量组和大剂量组墨汁推进率具有显著统计学意义(P＜0.05)。Compared with the normal control group, the ink advancing rate of the model control group was extremely statistically significant (P<0.01), indicating that the model preparation was established. Compared with the model control group, the ink advancing rate of sample 1# in each dose group increased, and the ink advancing rate of the medium-dose group and the high-dose group had significant statistical significance (P<0.05).
二、1#样品对小白鼠排便的影响2. The effect of sample 1# on the defecation of mice
1.原理1. Principle
经口灌胃给予造模药物复方地芬诺酯，建立小鼠便秘模型，测定小鼠的首粒排黑便的时间、6小时内排黑便粒数和排黑便重量，反应模型小鼠的排便情况。The modeling drug compound diphenoxylate was administered orally orally to establish a mouse model of constipation, and the time to the first black stool, the number of black stools and the weight of black stool discharged in 6 hours were measured, and the model mice were reflected Your bowel movements.
2.样品和仪器2. Samples and instruments
2.1样品和仪器2.1 Samples and instruments
2.1.1 1#样品：由清华德人西安幸福制药有限公司提供(芦荟-麦冬以5:9投料，加适量水煎煮提取，浓缩至500ml)，每1ml相当于总生药量0.4844g。2.1.1 Sample #1: Provided by Tsinghua Deren Xi'an Fortune Pharmaceutical Co., Ltd. (Aloe-Ophiopogon is fed at 5:9, decocted and extracted with an appropriate amount of water, and concentrated to 500ml). Each 1ml is equivalent to 0.4844g of total crude drug.
上述原液制备方法如下：The preparation method of the above-mentioned stock solution is as follows:
取芦荟、麦冬同时置多功能提取罐中，第1次加6～10倍量水，浸提4小时，第二次4～8倍量水，浸提3小时，汽压0.25～0.35MPa，温度80℃，滤过，合并滤液，减压浓缩，真空度为-0.06～-0.08MPa，汽压为0.25～0.35MPa，温度为60～70℃，浓缩至500ml，称之为原液。Take aloe vera and Ophiopogon japonicus at the same time and put them in a multifunctional extraction tank, add 6-10 times the amount of water for the first time, extract for 4 hours, and extract 4-8 times the amount of water for the second time, extract for 3 hours, vapor pressure 0.25～0.35MPa , Temperature 80℃, filter, combine the filtrate, concentrate under reduced pressure, vacuum degree is -0.06～-0.08MPa, vapor pressure is 0.25～0.35MPa, temperature is 60～70℃, and concentrated to 500ml, which is called original solution.
2.1.2仪器：手术剪、眼科镊、直尺、注射器、活性炭粉、阿拉伯树胶、复方地芬诺酯、量筒、蒸馏水、托盘、计时器。2.1.2 Instruments: surgical scissors, ophthalmic forceps, ruler, syringe, activated carbon powder, gum arabic, compound diphenoxylate, measuring cylinder, distilled water, tray, timer.
2.2试剂配制2.2 Reagent preparation
2.2.1 1#样品的配制2.2.1 Preparation of 1# sample
小剂量0.24ml/20ml/kg，取0.24ml原液加蒸馏水至20ml。Small dose 0.24ml/20ml/kg, take 0.24ml stock solution and add distilled water to 20ml.
中剂量2.40ml/20ml/kg，取2.40ml原液加蒸馏水至20ml。The medium dose is 2.40ml/20ml/kg, take 2.40ml stock solution and add distilled water to 20ml.
大剂量7.20ml/20ml/kg，取7.20ml原液加蒸馏水至20ml。Large dose of 7.20ml/20ml/kg, take 7.20ml stock solution and add distilled water to 20ml.
小鼠给药容积均为20ml/kg，每天1次。The administration volume of mice is 20ml/kg, once a day.
2.2.2墨汁的配制2.2.2 Preparation of ink
准确称取阿拉伯树胶50g，加水400ml，煮沸至溶液透明，称取活性炭(粉状)25g加至上述溶液中煮沸三次，待溶液凉后加水定容至500ml，于冰箱中4℃保存，用前摇匀。Accurately weigh 50g of gum arabic, add 400ml of water, and boil until the solution is transparent. Weigh 25g of activated carbon (powdered) and add to the above solution and boil three times. After the solution is cool, add water to make the volume up to 500ml and store in the refrigerator at 4°C before use. Shake well.
2.2.3浓度0.05％复方地芬诺酯的配制2.2.3 Preparation of 0.05% compound diphenoxylate
复方地芬诺酯片，每片含复方地芬诺酯2.5mg，取复方地芬诺酯片50mg(20片)，用研钵研碎后加蒸馏水至100ml，临用前配制。Compound diphenoxylate tablets, each containing 2.5mg compound diphenoxylate tablets, take 50mg (20 tablets) of compound diphenoxylate tablets, grind in a mortar and add distilled water to 100ml, and prepare before use.
3.实验方法3. Experimental method
3.1实验动物3.1 Experimental animals
昆明雄性小鼠60只，体重18～22g，购自西安交通大学实验动物中心。60 Kunming male mice weighing 18-22 g were purchased from the Experimental Animal Center of Xi'an Jiaotong University.
3.2实验步骤3.2 Experimental procedure
3.2.1实验动物分组及给药3.2.1 Grouping and administration of experimental animals
按小鼠体重随机分层分为空白对照组、模型对照组、1#样品小、中、大剂量组，共5个组，每组12只。空白对照组和模型对照组灌胃给蒸馏水，同样途径给予受试样品，给药容积20ml/Kg，连续10天，每天1次。According to the weight of the mice, they were randomly divided into blank control group, model control group, and 1# sample small, medium, and high-dose groups, a total of 5 groups, each with 12 mice. The blank control group and the model control group were given distilled water by gavage, and the test sample was given in the same way. The administration volume was 20ml/Kg, once a day for 10 consecutive days.
3.2.2模型的建立3.2.2 Model establishment
小鼠灌胃10天后，各组小鼠禁食不禁水16h。模型对照组和1#样品各剂量组灌胃给予复方地芬诺酯(5mg/kg BW)，空白对照组给蒸馏水。After the mice were given gastric administration for 10 days, the mice in each group were fasted without water for 16 hours. The model control group and 1# sample each dose group were given compound diphenoxylate (5mg/kg BW) by gavage, and the blank control group was given distilled water.
3.2.3指标测定的具体方法3.2.3 Specific methods for index determination
给复方地芬诺酯0.5小时后，阴性对照组和模型对照组小鼠用墨汁灌胃，剂量组给予含受试样品的墨汁，动物均单笼饲养，正常饮水进食。0.5 hours after the compound diphenoxylate was given, the mice in the negative control group and the model control group were gavaged with ink, and the dose group was given the ink containing the test sample. The animals were raised in single cages and drank and ate normally.
从灌墨汁开始，记录每只动物首粒排黑便时间、6小时内排黑便粒数及重量。From the ink filling, record the time of the first black stool, the number of black stools and the weight of each animal in 6 hours.
4.数据处理及结果判定4. Data processing and result judgment
数据可用方差分析，多个实验组和一个对照组均数的两两比较方法进行统计，详见下表2、表3和表4。The data can be counted by the analysis of variance and the pairwise comparison of the means of multiple experimental groups and a control group. See Table 2, Table 3, and Table 4 for details.
表2 1#样品对小鼠首粒排黑便时间的影响(
Figure PCTCN2020077630-appb-000004
n＝12) Table 2 The effect of 1# sample on the time of first defecation in mice (
Figure PCTCN2020077630-appb-000004
n=12)
Figure PCTCN2020077630-appb-000005
Figure PCTCN2020077630-appb-000005
注：与正常组比较 △P<0.01；与模型组比较 **P<0.01；与模型组比较 *P<0.05. Note: Compared with the normal group, △ P<0.01; compared with the model group ** P<0.01; compared with the model group * P<0.05.
与正常对照组比较，模型对照组首粒排黑便时间具有极显著统计学意义(P＜0.01)，说明模型制备成立。与模型对照组比较，1#样品各剂量组首粒排黑便时间缩短，但无统计学意义。Compared with the normal control group, the model control group's first black stool time has extremely significant statistical significance (P<0.01), indicating that the model preparation is established. Compared with the model control group, the time of first defecation in each dose group of 1# sample was shortened, but there was no statistical significance.
表3 1#样品对小鼠排黑便粒数的影响(
Figure PCTCN2020077630-appb-000006
n＝12) Table 3 Effect of 1# sample on the number of black stools in mice
Figure PCTCN2020077630-appb-000006
n=12)
Figure PCTCN2020077630-appb-000007
Figure PCTCN2020077630-appb-000007
注：与正常组比较 △P<0.05；与模型组比较 **P<0.01；与模型组比较 *P<0.05. Note: Compared with the normal group, △ P<0.05; compared with the model group ** P<0.01; compared with the model group * P<0.05.
与正常对照组比较，模型对照组排黑便粒数具有显著统计学意义(P＜0.05)，说明模型制备成立。与模型对照组比较，1#样品各剂量组排黑便粒数明显增加，中剂量和大剂量组具有显著统计学意义(P＜0.05)。Compared with the normal control group, the number of black stools in the model control group was statistically significant (P<0.05), indicating that the model was established. Compared with the model control group, the number of black stool particles in each dose group of sample 1# increased significantly, and the middle and high dose groups had significant statistical significance (P<0.05).
表4 1#样品对小鼠排黑便重量的影响(
Figure PCTCN2020077630-appb-000008
n＝12) Table 4 The effect of 1# sample on the weight of defecation in mice (
Figure PCTCN2020077630-appb-000008
n=12)
Figure PCTCN2020077630-appb-000009
Figure PCTCN2020077630-appb-000009
注：与正常组比较 △P<0.01；与模型组比较 **P<0.01；与模型组比较 *P<0.05. Note: Compared with the normal group, △ P<0.01; compared with the model group ** P<0.01; compared with the model group * P<0.05.
与正常对照组比较，模型对照组排黑便重量增加，但无统计学差异(P＞0.05)。与模型对照组比较，1#样品各剂量组排黑便重量均增加，但无统计学差异(P＞0.05)。Compared with the normal control group, the weight of defecation in the model control group increased, but there was no statistical difference (P>0.05). Compared with the model control group, the weight of black stool in each dose group of sample 1# increased, but there was no statistical difference (P>0.05).
5.结果判定：5. Result judgment:
根据小肠运动实验和排便时间任一项结果阳性，同时6小时内排黑便重量和粒数任一项结果阳性，可判定该项实验结果阳性。According to the positive results of the small intestine exercise test and the defecation time, and the positive results of any one of the weight and number of black stools within 6 hours, the test result can be determined as positive.
上述结果表明，与模型对照组比较，1#样品各剂量组墨汁推进率增大，中剂量组和大剂量组墨汁推进率具有显著统计学意义(P＜0.05)；与模型对照组比较，1#样品各剂量组排黑便粒数明显增加，中剂量组和大剂量组具有显著统计学意义(P＜0.05)。The above results show that, compared with the model control group, the ink advancing rate of sample 1# in each dose group increased, and the ink advancing rate of the medium-dose group and the high-dose group was statistically significant (P<0.05); compared with the model control group, 1 #Sample The number of black stools in each dose group increased significantly, and the middle dose group and the high dose group had significant statistical significance (P<0.05).
6.结论6 Conclusion
1#样品对小白鼠小肠蠕动和排便作用具有显著统计学意义(P＜0.05)。The 1# sample has significant statistical significance on intestinal peristalsis and defecation in mice (P<0.05).
实施例2Example 2
不同比例的中药组合物对润肠通便作用的影响Influence of different proportions of traditional Chinese medicine composition on moistening intestines and laxative effects
1原理：通过小鼠胃肠蠕动实验、小鼠排便实验结果证明本发明中中药组合物(芦荟和麦冬)比例的有益效果。1. Principle: The results of the mouse gastrointestinal peristalsis experiment and the mouse defecation experiment prove the beneficial effect of the ratio of the Chinese medicine composition (aloe and Ophiopogon japonicus) of the present invention.
1.1小鼠胃肠蠕动实验：经口灌胃给予造模药物复方地芬诺酯，建立小鼠小肠蠕动抑制模型，计算一定时间内小肠的墨汁推进率，判断模型小鼠胃肠蠕动功能。1.1 Gastrointestinal peristalsis experiment in mice: The model drug compound diphenoxylate was given by oral gavage to establish a mouse small intestinal peristalsis inhibition model, calculate the ink advancement rate of the small intestine within a certain period of time, and judge the gastrointestinal peristalsis function of the model mice.
1.2小鼠排便实验：经口灌胃给予造模药物复方地芬诺酯，建立小鼠便秘模型，测定小鼠的首粒排黑便的时间、6小时内排黑便粒数和排黑便重量，反应模型小鼠的排便情况。1.2 Mice defecation experiment: The model drug compound diphenoxylate was given by oral gavage to establish a mouse model of constipation, and the time of the first defecation of the mice, the number of black defecation and black defecation within 6 hours were measured The weight reflects the defecation of the model mice.
2样品和仪器2 samples and instruments
2.1样品和仪器2.1 Samples and instruments
2.1.1样品来源：清华德人西安幸福制药有限公司提供。2.1.1 Sample source: provided by Tsinghua Deren Xi'an Fortune Pharmaceutical Co., Ltd.
2.1.2样品制备2.1.2 Sample preparation
(1)比例Ⅰ样品：芦荟-麦冬以3：1投料，加适量水煎煮提取，浓缩至500ml，称之为原液Ⅰ。每1ml相当于总生药量的0.4844g。(1) Proportion I sample: aloe-Ophiopogon japonicus was fed at a ratio of 3:1, and an appropriate amount of water was added to decocting to extract, and then concentrated to 500ml, which was called the original liquid I. Each 1ml is equivalent to 0.4844g of the total crude drug.
(2)比例Ⅱ样品：芦荟-麦冬以5：9投料，加适量水煎煮提取，浓缩至500ml，称之为原液Ⅱ。每1ml相当于总生药量的0.4844g。(2) Proportion II sample: Aloe-Ophiopogon japonicus is fed at a ratio of 5:9, decocted and extracted with an appropriate amount of water, and concentrated to 500 ml, which is called the original liquid II. Each 1ml is equivalent to 0.4844g of the total crude drug.
(3)比例Ⅲ样品：芦荟-麦冬以1：6投料，加适量水煎煮提取，浓缩至500ml，称之为原液Ⅲ。每1ml相当于总生药量的0.4844g。(3) Proportion Ⅲ sample: Aloe-Ophiopogon japonicus is fed at a ratio of 1:6, decocted and extracted with an appropriate amount of water, and concentrated to 500ml, which is called the original solution Ⅲ. Each 1ml is equivalent to 0.4844g of the total crude drug.
2.1.2仪器：手术剪、眼科镊、直尺、注射器、活性炭粉、阿拉伯树胶、复方地芬诺酯、量筒、蒸馏水、托盘、计时器。2.1.2 Instruments: surgical scissors, ophthalmic forceps, ruler, syringe, activated carbon powder, gum arabic, compound diphenoxylate, measuring cylinder, distilled water, tray, timer.
2.2试剂配制2.2 Reagent preparation
2.2.11给药剂量设置2.2.11 Dosage setting
原液Ⅰ、原液Ⅱ、原液Ⅲ分别按照小、中、大剂量进行配制，方法如下：The original solution I, the original solution II, and the original solution III are prepared according to the small, medium and large doses respectively. The method is as follows:
(1)小剂量：0.24ml/20ml/kg，取0.24ml原液加蒸馏水至20ml。(1) Small dose: 0.24ml/20ml/kg, take 0.24ml stock solution and add distilled water to 20ml.
(2)中剂量：2.40ml/20ml/kg，取2.40ml原液加蒸馏水至20ml。(2) Middle dose: 2.40ml/20ml/kg, take 2.40ml stock solution and add distilled water to 20ml.
(3)大剂量：7.20ml/20ml/kg，取7.20ml原液加蒸馏水至20ml。(3) Large dose: 7.20ml/20ml/kg, take 7.20ml stock solution and add distilled water to 20ml.
小鼠给药容积均为20ml/kg，每天1次。The administration volume of mice is 20ml/kg, once a day.
2.2.2墨汁的配制2.2.2 Preparation of ink
准确称取阿拉伯树胶50g，加水400ml，煮沸至溶液透明，称取活性炭(粉状)25g加至上述溶液中煮沸三次，待溶液凉后加水定容至500ml，于冰箱中4℃保存，用前摇匀。Accurately weigh 50g of gum arabic, add 400ml of water, and boil until the solution is transparent. Weigh 25g of activated carbon (powdered) and add to the above solution and boil three times. After the solution is cool, add water to make the volume up to 500ml and store in the refrigerator at 4°C before use. Shake well.
2.2.3复方地芬诺酯溶液的配制2.2.3 Preparation of compound diphenoxylate solution
(1)0.025％复方地芬诺酯溶液：取复方地芬诺酯片10片(每片含复方地芬诺酯2.5mg)，用研钵研碎后加蒸馏水至100ml，临用前配制。(1) 0.025% compound diphenoxylate solution: take 10 compound diphenoxylate tablets (each tablet contains 2.5mg compound diphenoxylate), grind in a mortar and add distilled water to 100ml, and prepare before use.
(2)0.05％复方地芬诺酯溶液：取复方地芬诺酯片20片(每片含复方地芬诺酯2.5mg)，用研钵研碎后加蒸馏水至100ml，临用前配制。(2) 0.05% compound diphenoxylate solution: take 20 compound diphenoxylate tablets (each tablet contains 2.5 mg compound diphenoxylate), grind with a mortar and add distilled water to 100ml, and prepare before use.
3小鼠胃肠蠕动实验3 Mouse gastrointestinal motility experiment
3.1实验方法3.1 Experimental method
3.1.1实验动物3.1.1 Experimental animals
昆明雄性小鼠132只，体重18～22g，购自西安交通大学实验动物中心。132 Kunming male mice weighing 18-22 g were purchased from the Experimental Animal Center of Xi'an Jiaotong University.
3.1.2实验步骤3.1.2 Experimental procedure
3.1.2.1实验动物分组及给药3.1.2.1 Laboratory animal grouping and administration
按小鼠体重随机分层分为空白对照组、模型对照组、比例Ⅰ样品小、中、大剂量组、比例Ⅱ样品小、中、大剂量组、比例Ⅲ样品小、中、大剂量组，共11组，每组12只。空白对照组和模型对照组灌胃给蒸馏水，同样途径给予受试样品，给药容积20ml/Kg，连续10天，每天1次。Randomly divided into blank control group, model control group, ratio Ⅰ sample small, medium and high dose group, ratio Ⅱ sample small, medium and high dose group, and ratio Ⅲ sample small, medium and high dose group. There are 11 groups with 12 animals in each group. The blank control group and the model control group were given distilled water by gavage, and the test sample was given in the same way. The administration volume was 20ml/Kg, once a day for 10 consecutive days.
3.1.2.2模型的建立3.1.2.2 Model establishment
小鼠灌胃10天后，各组小鼠禁食不禁水16h。模型对照组和样品各剂量组灌胃给予0.025％复方地芬诺酯溶液(5mg/kg BW)，空白对照组给蒸馏水。After the mice were given gastric administration for 10 days, the mice in each group were fasted without water for 16 hours. The model control group and each dose group of the sample were given 0.025% compound diphenoxylate solution (5mg/kg BW) by gavage, and the blank control group was given distilled water.
3.1.2.3指标测定的具体方法3.1.2.3 Specific methods for index determination
给复方地芬诺酯0.5小时后，剂量组分别灌胃给予含相应受试样品的墨汁(含5％的活性炭粉、10％阿拉伯树胶)，空白和模型对照组给墨汁。25分钟后立即脱颈椎处死动物，打开腹腔分离肠系膜，剪取上端自幽门、下端至回盲部的肠管，置于托盘上，轻轻将小肠拉成直线，测量肠管长度为“小肠总长度”，从幽门至墨汁前言为“墨汁推进长度”。按下算式计算墨汁推进率(％)：0.5 hours after the compound diphenoxylate was given, the dose groups were given the ink containing the corresponding test sample (containing 5% activated carbon powder, 10% gum arabic) by intragastric administration, and the blank and model control groups were given ink. After 25 minutes, the animal was killed by removing the cervical vertebrae immediately, opening the abdominal cavity to separate the mesentery, cutting the upper end of the intestine from the pylorus, lower end to the ileocecal, and placing it on the tray, gently pulling the small intestine into a straight line, and measuring the length of the intestine as "total length of small intestine" , From the pylorus to the ink preface is "the length of ink advancing". Calculate the ink advance rate (%) according to the following formula:
Figure PCTCN2020077630-appb-000010
Figure PCTCN2020077630-appb-000010
3.2数据处理3.2 Data processing
数据用方差分析，多个实验组和一个对照组均数的两两比较方法进行统计，详见下表5。The data was calculated by analysis of variance, a pairwise comparison method of the means of multiple experimental groups and a control group. See Table 5 below for details.
表5 不同比例中药组合物对小鼠小肠蠕动的影响(
Figure PCTCN2020077630-appb-000011
n＝12) Table 5 The effect of different proportions of traditional Chinese medicine composition on intestinal peristalsis in mice (
Figure PCTCN2020077630-appb-000011
n=12)
Figure PCTCN2020077630-appb-000012
Figure PCTCN2020077630-appb-000012
Figure PCTCN2020077630-appb-000013
Figure PCTCN2020077630-appb-000013
注：与正常组比较 △P<0.01；与模型组比较 **P<0.01；与模型组比较 *P<0.05. Note: Compared with the normal group, △ P<0.01; compared with the model group ** P<0.01; compared with the model group * P<0.05.
3.3实验结果3.3 Experimental results
与正常对照组比较，模型对照组墨汁推进率具有极显著统计学意义(P＜0.01)，说明模型制备成立。与模型对照组比较，样品各剂量组墨汁推进率增大，其中比例Ⅰ样品的中、大剂量组，比例Ⅱ样品中、大剂量组，比例Ⅲ样品大剂量组墨汁推进率具有显著统计学意义(P＜0.05)。Compared with the normal control group, the ink advancing rate of the model control group was extremely statistically significant (P<0.01), indicating that the model preparation was established. Compared with the model control group, the ink advancing rate of each dose group of the sample increased. Among them, the proportion Ⅰ sample medium and high dose group, the proportion Ⅱ sample medium and high dose group, and the proportion Ⅲ sample high dose group had significant statistical significance. (P<0.05).
4小鼠排便实验4 Mouse bowel experiment
4.1实验方法4.1 Experimental method
4.1.1实验动物4.1.1 Experimental animals
昆明雄性小鼠132只，体重18～22g，购自西安交通大学实验动物中心。132 Kunming male mice weighing 18-22 g were purchased from the Experimental Animal Center of Xi'an Jiaotong University.
4.1.2实验步骤4.1.2 Experimental procedure
4.1.2.1实验动物分组及给药4.1.2.1 Laboratory animal grouping and administration
按小鼠体重随机分层分为空白对照组、模型对照组、比例Ⅰ样品小、中、大剂量组、比例Ⅱ样品小、中、大剂量组、比例Ⅲ样品小、中、大剂量组，共11个组，每组12只。空白对照组和模型对照组灌胃给蒸馏水，同样途径给予受试样品，给药容积20ml/Kg，连续10天，每天1次。Randomly divided into blank control group, model control group, ratio Ⅰ sample small, medium and high dose group, ratio Ⅱ sample small, medium and high dose group, and ratio Ⅲ sample small, medium and high dose group. A total of 11 groups, each with 12 animals. The blank control group and the model control group were given distilled water by gavage, and the test sample was given in the same way. The administration volume was 20ml/Kg, once a day for 10 consecutive days.
4.1.2.2模型的建立4.1.2.2 Model establishment
小鼠灌胃10天后，各组小鼠禁食不禁水16h。模型对照组和，样品各剂量组灌胃给予0.05％复方地芬诺酯溶液(5mg/kg BW)，空白对照组给蒸馏水。After the mice were given gastric administration for 10 days, the mice in each group were fasted without water for 16 hours. The model control group and each dose group of the samples were given 0.05% compound diphenoxylate solution (5mg/kg BW) by gavage, and the blank control group was given distilled water.
4.1.2.3指标测定的具体方法4.1.2.3 Specific methods for index determination
给复方地芬诺酯0.5小时后，空白对照组和模型对照组小鼠用墨汁灌胃，剂量组给予含受试样品的墨汁，动物均单笼饲养，正常饮水进食。0.5 hours after the compound diphenoxylate was administered, the blank control group and model control group mice were given ink gavage, and the dose group was given ink containing the test sample. The animals were raised in single cages and drank and ate normally.
从灌墨汁开始，记录每只动物首粒排黑便时间、6小时内排黑便粒数及重量。From the ink filling, record the time of the first black stool, the number of black stools and the weight of each animal in 6 hours.
4.2数据处理及结果判定4.2 Data processing and result judgment
数据可用方差分析，多个实验组和一个对照组均数的两两比较方法进行统计，详见下表6、表7和表8。The data can be counted using the analysis of variance and the pairwise comparison of the means of multiple experimental groups and a control group. For details, see Table 6, Table 7 and Table 8.
表6 不同比例中药组合物对小鼠首粒排黑便时间的影响(
Figure PCTCN2020077630-appb-000014
n＝12) Table 6 The effect of different proportions of traditional Chinese medicine composition on the time of first defecation in mice (
Figure PCTCN2020077630-appb-000014
n=12)
Figure PCTCN2020077630-appb-000015
Figure PCTCN2020077630-appb-000015
注：与正常组比较 △P<0.01；与模型组比较 **P<0.01；与模型组比较 *P<0.05. Note: Compared with the normal group, △ P<0.01; compared with the model group ** P<0.01; compared with the model group * P<0.05.
与正常对照组比较，模型对照组首粒排黑便时间具有极显著统计学意义(P＜0.01)，说明模型制备成立。与模型对照组比较，比例Ⅰ、Ⅱ、Ⅲ样品中剂量组和高剂量组首粒排黑便时间缩短，但无统计学意义。Compared with the normal control group, the model control group's first black stool time has extremely significant statistical significance (P<0.01), indicating that the model preparation is established. Compared with the model control group, the proportion of samples I, II, and III samples in the middle-dose group and the high-dose group shortened the time of first defecation, but there was no statistical significance.
表7 不同比例中药组合物对小鼠排黑便粒数的影响(
Figure PCTCN2020077630-appb-000016
n＝12) Table 7 The effect of different proportions of traditional Chinese medicine composition on the number of black stools in mice (
Figure PCTCN2020077630-appb-000016
n=12)
Figure PCTCN2020077630-appb-000017
Figure PCTCN2020077630-appb-000017
注：与正常组比较 △P<0.05；与模型组比较 **P<0.01；与模型组比较 *P<0.05. Note: Compared with the normal group, △ P<0.05; compared with the model group ** P<0.01; compared with the model group * P<0.05.
与正常对照组比较，模型对照组排黑便粒数具有显著统计学意义(P＜0.05)，说明模型制备成功。与模型对照组比较，比例Ⅰ、Ⅱ、Ⅲ样品各剂量组排黑便粒数明显增加，中剂量组和大剂量组具有显著统计学意义(P＜0.05)。Compared with the normal control group, the number of black stools in the model control group was statistically significant (P<0.05), indicating that the model was successfully prepared. Compared with the model control group, the number of black stool particles in each dose group of the proportions Ⅰ, Ⅱ, and Ⅲ samples increased significantly, and the middle dose group and the high dose group had significant statistical significance (P<0.05).
表8 不同比例中药组合物对小鼠排黑便重量的影响(
Figure PCTCN2020077630-appb-000018
n＝12) Table 8 The effect of different proportions of traditional Chinese medicine composition on the weight of black stool in mice (
Figure PCTCN2020077630-appb-000018
n=12)
Figure PCTCN2020077630-appb-000019
Figure PCTCN2020077630-appb-000019
注：与正常组比较 △P<0.01；与模型组比较 **P<0.01；与模型组比较 *P<0.05. Note: Compared with the normal group, △ P<0.01; compared with the model group ** P<0.01; compared with the model group * P<0.05.
与正常对照组比较，模型对照组排黑便重量增加，但无统计学差异(P＞0.05)。与模型对照组比较，比例Ⅰ、Ⅱ、Ⅲ样品各剂量组排黑便重量均增加，但无统计学差异(P＞0.05)。Compared with the normal control group, the weight of defecation in the model control group increased, but there was no statistical difference (P>0.05). Compared with the model control group, the weight of melena in each dose group of the proportions Ⅰ, Ⅱ and Ⅲ sample increased, but there was no statistical difference (P>0.05).
4.3实验结果4.3 Experimental results
根据小肠运动实验和排便时间任一项结果阳性，同时6小时内排黑便重量和粒数任一项结果阳性，可判定该项实验结果阳性。According to the positive results of the small intestine exercise test and the defecation time, and the positive results of any one of the weight and number of black stools within 6 hours, the test result can be determined as positive.
上述结果表明，与模型对照组比较，比例Ⅰ、Ⅱ、Ⅲ样品各剂量组墨汁推进率增大，中剂量组和大剂量组墨汁推进率具有显著统计学意义(P<0.05)；与模型对照组比较，比例Ⅰ、Ⅱ、Ⅲ样品各剂量组排黑便粒数明显增加，中剂量组和大剂量组具有显著统计学意义(P＜0.05)。The above results show that, compared with the model control group, the ink advancing rate of each dose group of the proportions Ⅰ, Ⅱ, and Ⅲ samples increased, and the ink advancing rate of the medium dose group and the high dose group was statistically significant (P<0.05); compared with the model Compared with the groups, the number of black stools in each dose group of the proportions Ⅰ, Ⅱ, and Ⅲ samples increased significantly, and the middle dose group and the high dose group had significant statistical significance (P<0.05).
5结论5 Conclusion
通过小鼠胃肠蠕动实验、小鼠排便实验结果可知，比例Ⅰ(3:1)、比例Ⅱ(5:9)、比例Ⅲ(1:6)均具有一定的润肠通便作用，其润肠通便作用强弱为比例Ⅰ(3:1)＞比例Ⅱ(5:9)＞比例Ⅲ(1:6)。Through the mouse gastrointestinal peristalsis experiment and the mouse defecation experiment, it can be known that the ratio I (3:1), the ratio II (5:9), and the ratio III (1:6) all have a certain degree of laxative effect. The intestinal laxative effect is ratio Ⅰ (3:1)> ratio Ⅱ (5:9)> ratio Ⅲ (1:6).
另外，考虑到芦荟-麦冬组合物安全性问题，应适当降低芦荟的占比，故比例Ⅱ(5:9)为最优比例。In addition, considering the safety of the aloe-Ophiopogon japonicus composition, the proportion of aloe should be appropriately reduced, so the ratio II (5:9) is the optimal ratio.
实施例3Example 3
中药组合物关于润肠通便作用的优势对比Comparison of advantages of traditional Chinese medicine composition on moistening and laxative effects
1.芦荟-麦冬中药组合物(实施例1中的1#样品)、芦荟-当归-麦冬-枳壳中药组合物(制备方法参见专利：一种改善胃肠道功能的中药组合物及其制备，专利号：ZL201110317780.9) 通过小鼠功能学实验证实，各组合物的中、大剂量均具有润肠通便功效。将各组样品的小鼠(以20g计)日摄入生药量计算统计(见表9)，由结果可知，在发挥润肠通便作用的前提下，芦荟-麦冬组的小鼠日摄入生药量低于芦荟-当归-麦冬-枳壳组。1. Aloe-Ophiopogon Chinese medicinal composition (sample 1 in Example 1), Aloe-Angelica-Ophiopogon japonicus-Fructus Aurantii Chinese medicinal composition (for the preparation method see patent: A Chinese medicinal composition for improving gastrointestinal function and Its preparation, patent number: ZL201110317780.9) It is confirmed by mouse functional experiments that the medium and large doses of each composition have the effect of moistening bowel and laxative. The daily intake of crude drugs in each group of mice (calculated as 20g) was calculated and calculated (see Table 9). From the results, it can be seen that under the premise that the aloe-Ophiopogon japonicus group The amount of imported medicines was lower than the aloe-angelica-Ophiopogon-Fructus Aurantii group.
表9 小鼠日摄入生药量(g)Table 9 Daily intake of crude drugs in mice (g)
Figure PCTCN2020077630-appb-000020
Figure PCTCN2020077630-appb-000020
2.芦荟-麦冬中药组合物中芦荟占比35.7％，芦荟-当归-麦冬-枳壳中药组合物中芦荟占比50.9％，芦荟的使用比例明显减少，提高了组合物的安全性，降低服药后产生副作用的风险。2. Aloe vera accounted for 35.7% in the aloe-Ophiopogon japonicus Chinese medicinal composition, and aloe vera accounted for 50.9% in the aloe-angelica-Ophiopogon japonicus-Fructus Aurantii Chinese medicinal composition. Reduce the risk of side effects after taking the medicine.
以上所述仅为本发明的优选实施例而已，并不用于限制本发明，对于本领域的技术人员来说，本发明可以有各种更改和变化。凡在本发明的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。The foregoing descriptions are only preferred embodiments of the present invention, and are not intended to limit the present invention. For those skilled in the art, the present invention can have various modifications and changes. Any modification, equivalent replacement, improvement, etc., made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims (10)

  1. 一种润肠通便的中药组合物，其特征在于，所述中药组合物的有效成分由原料药的提取物制成，所述原料药由质量比为2～5：1.5～12的芦荟和麦冬组成。An intestinal and laxative Chinese medicinal composition, characterized in that the active ingredient of the Chinese medicinal composition is made of extracts of raw materials, and the raw materials are composed of aloe vera with a mass ratio of 2-5:1.5-12 Composition of Ophiopogon.
  2. 根据权利要求1所述的中药组合物，其特征在于，所述原料药由质量比为5：9的芦荟和麦冬组成。The traditional Chinese medicine composition according to claim 1, wherein the raw material medicine is composed of aloe and Ophiopogon japonicus with a mass ratio of 5:9.
  3. 根据权利要求1所述的中药组合物，其特征在于，所述中药组合物还包括药学上可接受的辅料。The traditional Chinese medicine composition according to claim 1, wherein the traditional Chinese medicine composition further comprises pharmaceutically acceptable excipients.
  4. 根据权利要求3所述的中药组合物，其特征在于，所述的中药组合物的剂型为片剂、颗粒剂、胶囊剂、丸剂、栓剂、散剂、膏剂、滴剂、气雾剂、粉雾剂、溶液剂、混悬剂、糖浆剂、合剂、酒剂、茶剂、口含片、冻干粉针剂或乳剂。The traditional Chinese medicine composition according to claim 3, wherein the dosage form of the traditional Chinese medicine composition is tablet, granule, capsule, pill, suppository, powder, ointment, drop, aerosol, powder mist Preparations, solutions, suspensions, syrups, mixtures, wines, teas, lozenges, freeze-dried powder injections or emulsions.
  5. 根据权利要求1至4中任一项所述的中药组合物，其特征在于，所述的中药组合物通过以下步骤制备得到：The traditional Chinese medicine composition according to any one of claims 1 to 4, wherein the traditional Chinese medicine composition is prepared by the following steps:
    S1，取质量比为2～5：1.5～12的芦荟和麦冬置于提取罐中进行加水浸提，所述浸提的汽压为0.25～0.35MPa，温度为70～90℃，浸提完成后得到浸提液；S1: Take aloe and Ophiopogon japonicus with a mass ratio of 2～5:1.5～12 and place them in an extraction tank for water extraction. The vapor pressure of the extraction is 0.25～0.35MPa, the temperature is 70～90℃, and the extraction Obtain the extract after completion;
    S2，将所述浸提液进行减压浓缩，所述减压浓缩的真空度为-0.08～-0.06MPa，汽压为0.25～0.35MPa，温度为60～70℃，得到清膏；以及S2, concentrating the extract under reduced pressure, the vacuum degree of the reduced pressure concentration is -0.08～-0.06MPa, the vapor pressure is 0.25～0.35MPa, and the temperature is 60～70°C to obtain a clear paste; and
    S3，将所述清膏作为有效成分制备成所述润肠通便的中药组合物。S3, preparing the clear ointment as an active ingredient into the traditional Chinese medicine composition for moisturizing and laxative.
  6. 根据权利要求5所述的中药组合物，其特征在于，所述浸提分2次或多次进行。The traditional Chinese medicine composition according to claim 5, wherein the extraction is carried out in two or more times.
  7. 根据权利要求5所述的中药组合物，其特征在于，所述浸提包括：The traditional Chinese medicine composition according to claim 5, wherein the extraction comprises:
    第一次加6～10倍量水，浸提4小时；以及Add 6-10 times the amount of water for the first time and extract for 4 hours; and
    第二次4～8倍量水，浸提3小时；The second time is 4 to 8 times the amount of water, leaching for 3 hours;
    将第一次浸提得到的第一浸提液与第二次浸提得到的第二浸提液合并过滤后得到所述浸提液。The first extract obtained from the first extraction and the second extract obtained from the second extraction are combined and filtered to obtain the extract.
  8. 根据权利要求5所述的中药组合物，其特征在于，所述S3还包括，将所述清膏干燥、粉碎，得干膏粉，然后将所述干膏粉作为有效成分制备成所述润肠通便的中药组合物。The traditional Chinese medicine composition according to claim 5, wherein the S3 further comprises drying and pulverizing the clear ointment to obtain a dry ointment powder, and then using the dry ointment powder as an active ingredient to prepare the moisturizing agent Intestinal laxative Chinese medicine composition.
  9. 一种如权利要求1至8中任一项所述的中药组合物的制备方法，其特征在于，包括以下步骤：A method for preparing a traditional Chinese medicine composition according to any one of claims 1 to 8, characterized in that it comprises the following steps:
    S1，取质量比为2～5：1.5～12的芦荟和麦冬置于提取罐中进行加水浸提，所述浸提的汽压为0.25～0.35MPa，温度为70～90℃，浸提完成后得到浸提液；S1: Take aloe and Ophiopogon japonicus with a mass ratio of 2～5:1.5～12 and place them in an extraction tank for water extraction. The vapor pressure of the extraction is 0.25～0.35MPa, the temperature is 70～90℃, and the extraction Obtain the extract after completion;
    S2，将所述浸提液进行减压浓缩，所述减压浓缩的真空度为-0.08～-0.06MPa，汽压为0.25～0.35MPa，温度为60～70℃，得到清膏；以及S2, concentrating the extract under reduced pressure, the vacuum degree of the reduced pressure concentration is -0.08～-0.06MPa, the vapor pressure is 0.25～0.35MPa, and the temperature is 60～70°C to obtain a clear paste; and
    S3，将所述清膏作为有效成分制备成所述润肠通便的中药组合物；S3, preparing the clear ointment as an active ingredient into the traditional Chinese medicine composition for moisturizing and laxative;
    优选的，所述浸提分2次或多次进行；Preferably, the extraction is carried out in two or more times;
    更优选的，所述浸提包括：第一次加6～10倍量水，浸提4小时；以及第二次4～8倍量水，浸提3小时；将第一次浸提得到的第一浸提液与第二次浸提得到的第二浸提液合并过滤后得到所述浸提液；More preferably, the leaching includes: adding 6-10 times the amount of water for the first time, leaching for 4 hours; and the second time 4-8 times the amount of water, leaching for 3 hours; The first extract and the second extract obtained from the second extraction are combined and filtered to obtain the extract;
    进一步优选的，所述S3还包括，将所述清膏干燥、粉碎，得干膏粉，然后将所述作为有效成分制备成所述润肠通便的中药组合物。Further preferably, the S3 further includes drying and pulverizing the clearing ointment to obtain a dry ointment powder, and then preparing the active ingredient into the traditional Chinese medicine composition for laxative and laxative.
  10. 根据权利要求1至8中任一项所述的润肠通便的中药组合物在制备润肠通便的药物中的应用。Application of the traditional Chinese medicine composition for moisturizing and laxative according to any one of claims 1 to 8 in preparing a medicine for moisturizing and laxative.
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