CN1579485B - Traditional Chinese medicine composition for treating intestinal dysfunction and preparation method thereof - Google Patents

Abstract

The traditional Chinese medicine composition for treating intestinal dysfunction comprises the following components: 6-18 grams of Bupleurum bupleuri, 6-30 grams of white peony, 3-18 grams of heterophylla, and 6-15 grams of licorice. This basic formula can be directly used clinically without adding components; the extract of the above-mentioned traditional Chinese medicine composition can also be used as medicine; said extract refers to: a, extracting the volatile oil of the above-mentioned composition for future use; The composition is extracted with water, ethanol, or other organic solvents; c, purification and separation: water extract, vacuum concentration, ethanol precipitation, resin adsorption, resin exchange, high-speed centrifugation, cyclodextrin inclusion and other methods to obtain the extract; d. Combining the extracts of the above steps to form a pharmaceutical composition. Drugs such as Atractylodes macrocephala, Chuanxiong, Poria cocos, kudzu root, uncaria, Citrus aurantii or their extracts can also be added; or compounds such as smecta and domperidone. The present invention also provides a preparation method of the above medicine.

Description

Traditional Chinese medicine composition for treating intestinal dysfunction and preparation method thereof

technical field

The invention relates to a traditional Chinese medicine compound composition for treating diseases related to intestinal dysfunction and its modern preparation, as well as a process for preparing the pharmaceutical composition.

Background technique

Irritable bowel syndrome (IBS) is a common non-organic intestinal dysfunction disease of the digestive tract, with clinical characteristics of chronic recurrent attacks. The clinical symptoms are abdominal discomfort (abdominal pain, bloating) and abnormal intestinal motility, such as changes in bowel habits (diarrhea or constipation), abnormal stool properties (loose stools, mucus stools, or hard stools), and increased frequency of bowel movements. Existence or intermittent attacks, pathological examination mostly no specific intestinal inflammatory lesions, clinically divided into diarrhea type, constipation type, alternating type. Modern medicine believes that the pathogenesis of IBS is related to mental factors, changes in intestinal dynamics, improper diet, changes in colon secretion and absorption, and intestinal flora imbalance. The etiology and pathogenesis involve biology and social psychology (including tension Emotion, patient's personality and behavior) and other factors are recognized as a psychosomatic disease. The current treatment methods are limited, mostly starting from relaxation of intestinal smooth muscle, stimulation and antagonism of neurotransmitters, and anti-anxiety, with limited effects. And the drugs are often aimed at treating single symptoms such as diarrhea or constipation, mainly focusing on the regulation of intestinal microecology, antidepressant, prokinetic drug treatment, calcium channel antagonist and astringent treatment, etc. , diet, and individual quality. Although the above types of drugs can relieve some symptoms of irritable bowel syndrome, they all have one-sidedness and limitations in clinical application and cannot meet clinical requirements. However, in application, there are disadvantages such as no cure, large side effects, obvious individual differences, and high treatment costs.

No. 03112782.7 Chinese invention patent application discloses a "Chinese medicine composition and preparation for treating intestinal dysfunction diseases". The plan believes that mental factors are the primary cause of intestinal dysfunction, and should be treated with "holistic concept" and "syndrome differentiation" The principle provides the following formula: Bupleurum 6-15 grams, Paeoniae Alba 5-20 grams, Rhizoma Chuanxiong-10 grams, Atractylodes macrocephala 6-20 grams, Poria cocos 6-12 grams, licorice 5-20 grams. The idea and effect of this scheme are suitable for clinical practice, but based on experience, most manufacturers would like to further simplify the scheme in order to obtain a formula scheme and production process that are more suitable for industrialized mass production.

Contents of the invention

The invention comprehensively integrates multiple factors in the pathogenesis of the syndrome, and provides a traditional Chinese medicine compound composition for treating intestinal dysfunction diseases such as irritable bowel syndrome (IBS). The main clinical manifestations of IBS are diarrhea, constipation, abdominal pain, alternating diarrhea and constipation; accompanied by anorexia, fatigue, weight loss, poor sleep quality, irritability, etc. Modern medicine is divided into diarrhea type, constipation type, alternating type. Based on many years of clinical treatment and scientific research, the inventor of this project proceeds from the theory of traditional Chinese medicine and believes that the common and primary cause of IBS is mental factors. Patients often suffer from mental stress, depression, and irritability, and the disease is caused by the "seven emotions" of traditional Chinese medicine. Based on this, the relevant treatment principles and basic prescriptions that have been clinically verified are summarized.

The above-mentioned traditional Chinese medicine composition for treating intestinal dysfunction comprises:

Bupleurum 6-18 grams,

Paeoniae Alba 6-30 grams,

Pseudostellaria 6-18 grams,

Licorice 6-15 grams.

The proportions used in the above basic prescriptions are the proportions of various medicinal materials and drug combinations that can alleviate, relieve or cure relevant indications and regulate gastrointestinal function. The following ratios can be used according to the priority of clinical symptoms.

The basic square optimization amount 1 is:

Bupleurum 12-18 grams,

Paeoniae Alba 12-30 grams,

Pseudostellaria 6-12 grams,

Licorice 6-12 grams.

The basic square optimization amount 2 is:

Bupleurum 9-12 grams,

Paeoniae Alba 9-12 grams,

Pseudostellaria 6-12 grams,

Licorice 6-12 grams.

The above basic methods can be implemented in the following ways:

1. Do not add any components, directly use it in clinic: the composition is the formula;

2. Using the extract of the above-mentioned traditional Chinese medicine composition as a medicine;

3. Add other ingredients on the basis of the above basic formula;

4. Adding other ingredients on the basis of the extract of the above-mentioned traditional Chinese medicine composition.

The above items 2, 3, and 4 are explained as follows:

Wherein "using the extract of the above-mentioned traditional Chinese medicine composition as a medicine", the "extract" refers to:

A, extract the volatile oil of above-mentioned composition for subsequent use;

b. The composition after the above-mentioned extraction of volatile oil is extracted with water, ethanol, or other organic solvents;

c. The composition extracted with water, ethanol, or other organic solvents, the extract obtained by vacuum concentration, ethanol precipitation, resin adsorption, resin exchange, high-speed centrifugation, cyclodextrin inclusion, etc. alone or in combination;

d. Combining the extracts of the above steps to form a pharmaceutical composition.

Volatile oil part (ingredient combination 1): the volatile oily substance extracted by steam distillation after the prescription drug is pulverized. The yield is 0.5-3% of the medicinal material weight. Through GC-MS analysis, it contains multiple components (in descending order of content) including:

Atractylon, Butenolide A, Butenolide B, Ligustilide and its derivatives, 3-β-Acetoxyatractylon ), apirene, atractyl alcohol, etc. Animal pharmacodynamic studies have shown that it can significantly inhibit the hyperfunction of the small intestine caused by neostigmine-loaded mice, and improve the suppressed state of small intestine function caused by atropine: it can significantly promote intestinal propulsion in normal mice, and increase spleen index and thymus index in mice with spleen deficiency , significantly reduced the number of writhing in mice induced by acetic acid. Experiments on the influence of reserpine-induced gastrointestinal dysfunction in rats: After continuous modeling with reserpine in rats, the body weight, food intake, thymus index, spleen index, MTL levels in plasma and jejunum homogenate were correlated with Compared with the normal control group, it was significantly lower (P<0.01). Compared with the model group, the administration groups of components and composition extracts from different parts can improve the above conditions to varying degrees, in which body weight, food intake, thymus index, plasma and MTL levels in jejunum homogenate. Mucosa damage test: There were significant differences between the administration group and the model group in the components of different parts and composition extracts (P<0.05).

Components extracted from dichloromethane (component combination 2): the composition of the chemical components obtained by extracting dichloromethane from the insoluble part of petroleum ether for prescription drugs and silica gel chromatography.

After analysis by HPLC, TLC, IR, NHR, MS, UV, etc., it mainly contains more than 3 kinds of alkaloid chemical components including: tetramethylpyrazine-ligustrazine (tetramethylpyrazine-TMP), isoleucyl knotamine Acid lactam, Perlolyrine. Animal pharmacodynamic studies have shown that it can significantly inhibit the hyperfunction of the small intestine caused by neostigmine-loaded mice, and improve the suppressed state of small intestine function caused by atropine: increase the spleen index and thymus index of mice with spleen deficiency, and significantly reduce the mice caused by acetic acid. Number of twists. Experiments on the influence of reserpine-induced gastrointestinal dysfunction in rats: After continuous modeling with reserpine in rats, the body weight, food intake, thymus index, spleen index, MTL levels in plasma and jejunum homogenate were correlated with Compared with the normal control group, it was significantly lower (P<0.01). Compared with the model group, the administration groups of components and composition extracts from different parts can improve the above conditions to varying degrees, in which body weight, food intake, thymus index, plasma and MTL levels in jejunum homogenate. Mucosa damage test: There were significant differences between the administration group and the model group in the components of different parts and composition extracts (P<0.05).

Ethyl acetate extraction site components: prescription drugs are extracted from dichloromethane insoluble parts with ethyl acetate, and the composition of chemical components obtained after silica gel chromatography. There are two groups: EtOAC1 component group and EtOAC2 component group.

EtOAC1 (component combination 3): It mainly contains 5 kinds of phenolic chemical components through HPLC, TLC, IR, NHR, MS, UV and other analysis. Ferulic acid, chuanxiongolide, chuanxiongol, chrysophanol, paeonel.

Animal pharmacodynamic studies have shown that it can significantly inhibit the hyperfunction of the small intestine caused by neostigmine-loaded mice, and improve the suppressed state of small intestine function caused by atropine: it can significantly promote intestinal propulsion in normal mice, and increase spleen index and thymus index in mice with spleen deficiency , significantly reduced the number of writhing in mice induced by acetic acid. Experiments on the influence of reserpine-induced gastrointestinal dysfunction in rats: After continuous modeling with reserpine in rats, the body weight, food intake, thymus index, spleen index, MTL levels in plasma and jejunum homogenate were correlated with Compared with the normal control group, it was significantly lower (P<0.01). Compared with the model group, the administration groups of components and composition extracts from different parts can improve the above conditions to varying degrees, in which body weight, food intake, thymus index, plasma and MTL levels in jejunum homogenate. Mucosa damage test: There were significant differences between the administration group and the model group in the components of different parts and composition extracts (P<0.05).

EtOAC2 (component combination four). Analyzed by HPLC, TLC, IR, NHR, MS, UV, etc., it mainly contains the following chemical components. Saikogenin A-G (saikogenin A-G), glycyrrhetinic acid, liquiritigenin, isoliquiritigenin, kaempferol, isoliquiritigenin, quercetin (quercetin), different quercetin (isoquercetin), different rhamnetin (isorhamnetin) and so on. Animal pharmacodynamic studies have shown that it can significantly inhibit the hyperfunction of the small intestine caused by neostigmine-loaded mice, and improve the suppressed state of small intestine function caused by atropine: it can significantly promote intestinal propulsion in normal mice, and increase spleen index and thymus index in mice with spleen deficiency , significantly reduced the number of writhing in mice induced by acetic acid. Experiments on the influence of reserpine-induced gastrointestinal dysfunction in rats: After continuous modeling with reserpine in rats, the body weight, food intake, thymus index, spleen index, MTL levels in plasma and jejunum homogenate were correlated with Compared with the normal control group, it was significantly lower (P<0.01). Compared with the model group, the administration groups of components and composition extracts from different parts can improve the above conditions to varying degrees, in which body weight, food intake, thymus index, plasma and MTL levels in jejunum homogenate. Mucosa damage test: There were significant differences between the administration group and the model group in the components of different parts and composition extracts (P<0.05).

Relevant components of the n-butanol extraction part: the composition of chemical components obtained by extracting n-butanol from the insoluble part of ethyl acetate and silica gel chromatography for prescription drugs. There are two groups: BuoH1 component group and BuoH2 component group.

BuoH1 (component combination five): analyzed by HPLC, TLC, IR, NHR, MS, UV, etc. It mainly contains flavonoids and their glycosides: New Zealand vitexin II, liquiritin, isoliquiritin, new Liquiritin (neoliquiritin), isoliquiritigenin (isoliquiritigenin), rutin (Rutin), glycosides of kaempferol: kaempferitrin, kaempferol-7-rhamnoside , kaempferol-3-0-α-L-arabinofuranoside-7-0-α-L-rhamnopyranoside, narcissin. Animal pharmacodynamic studies have shown that it can significantly inhibit the hyperfunction of the small intestine caused by neostigmine-loaded mice, and improve the suppressed state of small intestine function caused by atropine: it can significantly promote intestinal propulsion in normal mice, and increase spleen index and thymus index in mice with spleen deficiency , significantly reduced the number of writhing in mice induced by acetic acid. Experiments on the influence of reserpine-induced gastrointestinal dysfunction in rats: After continuous modeling with reserpine in rats, the body weight, food intake, thymus index, spleen index, MTL levels in plasma and jejunum homogenate were correlated with Compared with the normal control group, it was significantly lower (P<0.01). Compared with the model group, the administration groups of components and composition extracts from different parts can improve the above conditions to varying degrees, in which body weight, food intake, thymus index, plasma and MTL levels in jejunum homogenate. Mucosa damage test: There were significant differences between the administration group and the model group in the components of different parts and composition extracts (P<0.05).

BuoH2 (ingredient combination six). Through HPLC, TLC, IR, NHR, MS, UV and other analysis, the main chemical components containing saponins or terpene glycosides: glycyrrhizin (glycyrrhizin), glycyrrhizin A-K (glycyrrhizin A-K), saikosaponin A-F (saikosaponin A-F), paeoniflorin (paeoniflorin), paeoniflorin (paeonin), paeoniflorin (albiforin), oxidized paeoniflorin (oxypaeoniflorin), hydroxypaeoniflorin, benzoylpaeoniflorin (benzoylpaeoniflorin), paeonoside (paeonoside) heterophylla saponin A ( pseudostellarinoside A), acutifoliside D (acutifoliside D). Animal pharmacodynamic studies have shown that it can significantly inhibit the hyperfunction of the small intestine caused by neostigmine-loaded mice, and improve the suppressed state of small intestine function caused by atropine: it can significantly promote intestinal propulsion in normal mice, and increase spleen index and thymus index in mice with spleen deficiency , significantly reduced the number of writhing in mice induced by acetic acid. Experiments on the influence of reserpine-induced gastrointestinal dysfunction in rats: After continuous modeling with reserpine in rats, the body weight, food intake, thymus index, spleen index, MTL levels in plasma and jejunum homogenate were correlated with Compared with the normal control group, it was significantly lower (P<0.01). Compared with the model group, the administration groups of components and composition extracts from different parts can improve the above conditions to varying degrees, in which body weight, food intake, thymus index, plasma and MTL levels in jejunum homogenate. Mucosa damage test: There were significant differences between the administration group and the model group in the components of different parts and composition extracts (P<0.05).

Water-soluble components (ingredient combination seven): Prescription drugs are extracted from the n-butanol insoluble part with purified water, and the total polysaccharides are obtained after ethanol precipitation, tannic acid or ion exchange resin deproteinization, and are subjected to Sephadex gel chromatography ( Sephadex G-100) treatment to obtain individual components with molecular weights of 150000, 120000, 90000, 46000, 32000, 15000, after hydrolysis, galactose, glucose, rhamnose, arabinose, and galacturaldehyde were detected by paper chromatography acid, glucuronic acid. Analyzed by HPLC, TLC, IR, NHR, MS, UV, etc., which mainly contain pachymic acid, β-pachyman, β-pachymaran, and glycyrrhizan UC. Composition of polysaccharide macromolecular components. Animal pharmacodynamic studies have shown that it can significantly inhibit the hyperfunction of the small intestine caused by neostigmine-loaded mice, and improve the suppressed state of small intestine function caused by atropine: it can significantly promote intestinal propulsion in normal mice, and increase spleen index and thymus index in mice with spleen deficiency , significantly reduced the number of writhing in mice induced by acetic acid. Experiments on the influence of reserpine-induced gastrointestinal dysfunction in rats: After continuous modeling with reserpine in rats, the body weight, food intake, thymus index, spleen index, MTL levels in plasma and jejunum homogenate were correlated with Compared with the normal control group, it was significantly lower (P<0.01). Compared with the model group, the administration groups of components and composition extracts from different parts can improve the above conditions to varying degrees, in which body weight, food intake, thymus index, plasma and MTL levels in jejunum homogenate. Mucosa damage test: There were significant differences between the administration group and the model group in the components of different parts and composition extracts (P<0.05).

The following extraction schemes can be used to obtain different combinations of the above components:

Extract E and its components: the traditional Chinese medicine compound composition is extracted with water, after being properly concentrated, ethanol of different concentrations is added, left to stand, centrifuged, and the supernatant is concentrated to obtain. Analysis by HPLC, TLC, IR, NHR, MS, UV, etc. mainly contains component combinations 2, 3, 4, 5, and 6. The total solid yield is 14-18% of the medicinal material weight.

Extract S and components: The Chinese medicine compound composition is extracted with water, and after being properly concentrated, multiple combinations of components with different polarities are obtained through silica gel column chromatography for multiple times, and are tested by HPLC, TLC, IR, NHR, MS, UV Etc analysis is component combination 2, 3, 4, 5, 6, 7 respectively.

Extract L and its components: the Chinese medicine compound composition is extracted with water, and exchanged and adsorbed by an ion exchange column to obtain a number of different component combinations. Analysis by HPLC, TLC, IR, NHR, MS, UV, etc., which are component combinations 2, 3, 4, and 5, respectively.

Extract G and its components: the Chinese medicine compound composition is extracted with water, after being properly concentrated and processed by high-speed centrifugation, the component is dissolved in the aqueous solution. A number of different ingredient combinations are obtained. Analysis by HPLC, TLC, IR, NHR, MS, UV, etc., which are component combinations 2, 3, 4, and 5, respectively. The total solid yield is 18-24% of the medicinal material weight.

Extract D and its components: the Chinese medicine compound composition is extracted with water, and then eluted after being adsorbed by a macroporous adsorption resin to obtain a number of different component combinations. Analyzed by HPLC, TLC, IR, NHR, MS, UV, etc., which are component combinations 2, 3, 4, 5, 6, and 7, respectively. The solid yield is 2.0-7.0% of the medicinal material weight.

Extract C and its components: The Chinese medicine compound composition is extracted with water, concentrated properly, subjected to high-speed centrifugation and ultrafiltration to obtain different component combinations, which are analyzed by HPLC, TLC, IR, NHR, MS, UV, etc. Combinations two, three, four, five, six, seven. The total solid yield is 10-15% of the medicinal material weight.

Steam distillate and components: the volatile oily substance extracted from the traditional Chinese medicine compound composition by steam distillation, and the yield is 1-3% of the weight of the medicinal material. GC-MS analysis contained component combination 1 therein. It is solidified and stored by β-cyclodextrin inclusion.

It should be noted that the above-mentioned components are only the main components of the "extract", and the actual components are not limited thereto. The "extract" should be limited by its raw materials and extraction methods.

As mentioned in the above items 3 and 4, "Add other ingredients on the basis of the above basic prescription; add other ingredients on the basis of the extract of the above-mentioned traditional Chinese medicine composition", the components that can be added include the following four types of drugs: Any one or more. The botanical medicines can be various processed products prepared from corresponding plants (plant species specified in the Chinese Pharmacopoeia) as raw materials.

The first class of drugs that can be added: 1 or 2 or 3 of Atractylodes macrocephala, Chuanxiong, Poria, Citrus aurantium, Guizhi, Chenpi, Fangfeng, Angelica, Pinellia, Coptis, Rhubarb, Scutellaria, and Albizia Bark, each The dosage of the components is according to the general dosage stipulated in the Pharmacopoeia, or the following specific prescription dosage.

The addition of such drugs can constitute the following options:

Prescriptions 1 to 5 are mainly used for different degrees of diarrhea, constipation, abdominal pain, alternating diarrhea and constipation.

1. Bupleurum 9 grams, white peony root 9 grams, heterophylla 6 grams, licorice 6 grams.

2. 12 grams of bupleurum, 12 grams of white peony root, 6 grams of heterophylla, and 6 grams of licorice.

3. 15 grams of Bupleurum, 18 grams of white peony root, 9 grams of heterophylla, and 9 grams of licorice.

4. 12 grams of Bupleurum, 27 grams of white peony root, 6 grams of heterophylla, and 9 grams of licorice.

5. 9 grams of Bupleurum, 9 grams of white peony, 6 grams of heterophylla, 9 grams of Atractylodes macrocephala, and 6 grams of licorice.

Prescriptions 6 to 10 are mainly used for different degrees of diarrhea, constipation, abdominal pain, alternating diarrhea and constipation, accompanied by severe diarrhea and pain symptoms.

6. 9 grams of Bupleurum, 9 grams of white peony, 6 grams of Chuanxiong, 6 grams of heterophylla, and 6 grams of licorice.

7. 9 grams of Bupleurum, 18 grams of white peony root, 6 grams of heterophylla, 9 grams of licorice, and 9 grams of tangerine peel.

8. Bupleurum 9 grams, Radix Paeoniae Alba 9 grams, Radix Pseudostellariae 6 grams, Licorice 6 grams, Citrus aurantium 9 grams.

9. 9 grams of Bupleurum, 9 grams of white peony root, 6 grams of heterophylla, 6 grams of licorice, and 9 grams of skullcap.

10. 9 grams of Bupleurum, 12 grams of white peony root, 6 grams of heterophylla, 6 grams of licorice, 6-9 grams of tangerine peel, and 6-9 grams of Fangfeng.

Prescriptions 11 to 17 are mainly used for diarrhea, constipation or alternating diarrhea and constipation, accompanied by symptoms such as poor sleepiness and irritability in varying degrees.

11. Bupleurum 9 grams, Radix Paeoniae Alba 9 grams, Radix Pseudostellariae 6 grams, Licorice 6 grams, Atractylodes macrocephala 9 grams, Fangfeng 6-9 grams.

12. 9 grams of Bupleurum, 9 grams of white peony, 6 grams of heterophylla, 6 grams of licorice, 9 grams of Atractylodes macrocephala, and 6-9 grams of berberine.

13. 9 grams of Bupleurum, 9 grams of white peony, 6 grams of heterophylla, 6 grams of licorice, 9 grams of Atractylodes macrocephala, and 9 grams of Poria.

14. Bupleurum 9 grams, Radix Paeoniae Alba 9 grams, Radix Pseudostellariae 6 grams, Licorice 6 grams, Albizia Julibrissin 9 grams.

15. Bupleurum 9 grams, Radix Paeoniae Alba 9 grams, Radix Pseudostellariae 6 grams, Licorice 6 grams, Citrus aurantium 6 grams.

16. 9 grams of Bupleurum, 9 grams of white peony root, 6 grams of heterophylla, 6 grams of licorice, 9 grams of Poria, and 9 grams of Atractylodes macrocephala.

17. 9 grams of Bupleurum, 9 grams of white peony root, 6 grams of heterophylla, 6 grams of licorice, and 6 grams of Chuanxiong.

18. 9 grams of Bupleurum, 9 grams of white peony root, 6 grams of heterophylla, 6 grams of licorice, 6 grams of rhubarb, and 3 grams of pinellia.

Prescriptions 19-24 are mainly used for diarrhea, constipation or alternating diarrhea and constipation, accompanied by symptoms such as abdominal distension, anorexia, and irritability in varying degrees

19. 9 grams of Bupleurum, 9 grams of white peony, 6 grams of heterophylla, 9 grams of Atractylodes macrocephala, 6 grams of licorice, and 6 grams of aurantium.

20. 9 grams of Bupleurum, 9 grams of white peony, 6 grams of heterophylla, 6 grams of licorice, 9 grams of Atractylodes macrocephala, and 6-9 grams of berberine.

21. 9 grams of bupleurum, 9 grams of white peony root, 6 grams of heterophylla, 6 grams of licorice, 6 grams of tangerine peel, and 6 grams of aurantium.

22. 9 grams of Bupleurum, 9 grams of white peony, 6 grams of heterophylla, 9 grams of Atractylodes macrocephala, 6 grams of licorice, 9 grams of skullcap, and 9 grams of tangerine peel.

23. 9 grams of Bupleurum, 9 grams of white peony, 6 grams of heterophylla, 9 grams of Atractylodes macrocephala, 6 grams of licorice, and 9 grams of Fangfeng.

24. Bupleurum 9 grams, Radix Paeoniae Alba 9 grams, Radix Pseudostellariae 6 grams, Atractylodes macrocephala 9 grams, Licorice 6 grams, Rhizoma Chuanxiong 6 grams, Poria cocos 9 grams.

Prescriptions 25 to 28 are mainly used for diarrhea, constipation or alternating diarrhea and constipation, accompanied by varying degrees of emaciation and chills.

25. Bupleurum 9 grams, Radix Paeoniae Alba 9 grams, Radix Pseudostellariae 6 grams, Atractylodes macrocephala 9 grams, Licorice 6 grams, Rhizoma Chuanxiong 6 grams.

26. 9 grams of Bupleurum, 9 grams of white peony, 6 grams of heterophylla, 9 grams of Atractylodes macrocephala, 6 grams of licorice, 6 grams of angelica, and 3 grams of coptis.

27. 9 grams of Atractylodes macrocephala, 9 grams of poria, 6 grams of licorice, 6 grams of Bupleurum, 6 grams of heterophylla, 12 grams of white peony, and 9 grams of astragalus.

28. 9 grams of Bupleurum, 9 grams of white peony, 6 grams of heterophylla, 9 grams of Atractylodes macrocephala, 6 grams of licorice, and 6 grams of cassia twig.

The second class of drugs that can be added: it can be the extract of one or some drugs in the above first class of drugs (extracts of water, ethanol or organic solvents of various pharmaceutical compositions, one or more extracts or Combinations of chemical components. Combinations of extracts that include one or more extracts of different drug combinations.)

The extract of one or some drugs (also known as: "the combination of chemical components of different polarities of the drug and the combination of chemical components obtained by different separation methods") refers to: the volatile oil part, the water extract part The dichloromethane extract fraction in the dichloromethane insoluble fraction, the ethyl acetate extract fraction in the dichloromethane insoluble fraction, the n-butanol extract fraction in the ethyl acetate insoluble fraction, and the water-soluble fraction in the n-butanol insoluble fraction. See schematic diagram (Figure 1). Purification, separation and drying: water extract, vacuum concentration, ethanol precipitation, resin adsorption, resin exchange, high-speed centrifugation, cyclodextrin inclusion and other technical methods obtained alone or in combination. See schematic diagram (Figure 2).

A third class of drugs that can be added: compounds that can be of natural origin or artificially synthesized.

For example, one of the following drugs is added to the composition: 2-10g of SEMECDA, 5-20mg of domperidone, 1-20mg of cisapride, 2-15mg of Tegaserod, Alosetron 0.5-3mg, Spasmomen 50-200mg, Pinaverum bromide 50-200mg, Trimebutine 0.2-1.5g, Butyric acid Bacteria 40-200mg, etc.

The preparation method of the above-mentioned Chinese medicine composition (and modern dosage form) for the treatment of intestinal dysfunction, the steps are as follows:

1. The above composition is extracted with water, ethanol, or other organic solvents;

2. Use one or more of the following methods to purify and separate the above-mentioned composition extracted by water, ethanol, or other organic solvents: vacuum concentration, ethanol precipitation, resin adsorption, resin exchange, high-speed centrifugation, cyclodextrin inclusion, etc. The extract is obtained after the technical method is processed;

3. Combine the above extracts, add appropriate pharmaceutical excipients directly or after purification and separation, and prepare them into granules, capsules, tablets, oral liquids, injections (subcutaneous, blood vessel, intramuscular administration), transdermal or Transmucosal formulation, suppository for rectal administration; or follow step 4:

4. Granules, capsules, tablets, preparations for transdermal or transmucosal administration, and suppositories for rectal administration prepared by adding appropriate pharmaceutical excipients to the above drugs after crushing.

The scope of indications of the above Chinese medicine composition:

Gastrointestinal disorders in humans or other mammals. Include:

1. Irritable bowel syndrome (bowel dysfunction) induced by mental factors.

2. Irritable bowel syndrome (bowel dysfunction) induced by food or inflammation

3. The main clinical manifestations of IBS are diarrhea, constipation, abdominal pain, alternating diarrhea and constipation; accompanied by anorexia, fatigue, weight loss, poor sleep quality, irritability, etc. Modern medicine is divided into diarrhea type and constipation type. The main manifestations of clinical symptoms are irregular abdominal pain, abdominal distension, diarrhea, changes in stool properties and increased frequency of defecation. Exclude other intestinal organic diseases: exclude thyroid disease, diabetes, kidney disease, cardiovascular disease, hematopoietic system disease, ulcerative colitis, Crohn's disease, chronic dysentery, peptic ulcer, chronic hepatitis, anal disease, etc., to prevent false positives . Generally, it has the following characteristics: (1) abdominal pain before defecation, relieved after defecation; (2) intestinal peristalsis significantly increased during abdominal pain; (3) constipation or diarrhea; (4) generally good general condition or accompanied by systemic neurosis. (5) The spontaneous peristalsis of the colon is abnormal and the intestinal sensitivity is increased. (6) Visceral hyperalgesia, etc.

4. Related diseases include: functional bowel disorder (functional diarrhea, functional constipation), acute and chronic functional abdominal pain or bloating or accompanied by gastric symptoms, periodic abdominal pain or bloating, functional dyspepsia, stomach pain and stomach discomfort wait.

The results of the animal pharmacodynamics study of the composition of the present invention (comprising the above-mentioned, by extracts or various combinations containing chemical drugs):

The results of pharmacodynamic experiments show that:

1. Experiments on the influence of mice with spleen deficiency. The components and composition extracts of different parts can significantly increase the body weight and food intake of mice with spleen deficiency to varying degrees, improve the signs and loose stools of mice with spleen deficiency, and increase the spleen quality of mice with spleen deficiency. Index and thymus index, which regulate the gastrointestinal function of mice with spleen deficiency, were significantly different from those in the model group (P<0.05).

2. Experiments on the effects of neostigmine-loaded/atropine-loaded small intestine propulsion in mice: components and composition extracts from different parts can significantly inhibit the hyperfunction of the small intestine caused by neostigmine-loaded mice, Compared with the model group, it can improve the inhibited state of small intestinal function caused by atropine (P<0.05), suggesting that it has a two-way regulating effect on intestinal function.

3. Experiments on the effect of acetic acid-induced writhing pain in mice: components and composition extracts from different parts can significantly reduce the number of writhing times in mice caused by acetic acid to varying degrees.

4. Experiments on the effect of reserpine-induced gastrointestinal dysfunction in rats: After continuous modeling with reserpine in rats, body weight, food intake, thymus index, spleen index, MTL levels in plasma and jejunum homogenate Compared with the normal control group, it was significantly lower (P<0.01). Compared with the model group, the administration groups of components and composition extracts from different parts can improve the above conditions to varying degrees, in which body weight, food intake, thymus index, plasma and MTL levels in jejunum homogenate.

5. Membrane damage test: Compared with the model group, there were significant differences (P<0.05) between the administration group of components and composition extracts in different parts.

Experimental Methods and Results

1. Effect of composition extract on mice with spleen deficiency:

Sixty Kunming male mice were randomly divided into 6 groups. Except for the normal control group, all other groups were given rhubarb water decoction to replicate the mouse model of spleen deficiency. Continuous intragastric administration for 6 days. 0.1g·kg ^-1 ·d ^-1 . The components and composition extracts of different parts were compared with the model group, and the inter-group t test was carried out. Compared with the positive drug group and the model group, it can significantly increase the body weight and food intake of mice with spleen deficiency to varying degrees, improve the signs and loose stools of mice with spleen deficiency, increase the spleen index and thymus index of mice with spleen deficiency, and regulate the Gastrointestinal function. The results are shown in Table 2.

The influence of table 2 composition extract on mice with spleen deficiency (X ± S)

Compared with the control group: ^△ P<0.05, ^△△ P<0.01. Compared with the model group: ^* P<0.05, ^** P<0.01.

2. The effect of the composition extract on the small intestine propulsion of mouse neostigmine load/atropine load:

Sixty Kunming mice were randomly divided into 6 groups according to body weight. Oral administration, continuous 5d. Except for the normal control group, the mice in other groups were subcutaneously injected with neostigmine 1 mg·kg ^-1 . All mice were fed with 5% carbon powder 0.1ml·10g ^-1 , sacrificed by laparotomy, and the gastrointestinal tract was taken out. The distance from the front of the carbon ink to the pylorus was recorded, and its percentage in the total length of the small intestine was calculated. The components and composition extracts of different parts were compared with the model group, and the inter-group t test was carried out. In addition, the method of atropine-loaded intestinal propulsion test was the same as that of neostigmine-loaded small-intestine propulsion test, except that the model group and the treatment group were subcutaneously injected with atropine 5 mg·kg ^-1 load. The results are shown in Table 3.

Compared with the model group, the administration group and the positive drug group can significantly inhibit the hyperfunction of the small intestine caused by neostigmine-loaded mice to varying degrees, and improve the inhibited state of small intestine function caused by atropine, suggesting that it has a two-way regulation on intestinal function effect.

The effect of table 3 composition extract on the small intestine propulsion of mouse neostigmine load/atropine load (X ± S)

Compared with the control group: ^△ P<0.05, ^△△ P<0.01. Compared with the model group: ^* P<0.05, ^** P<0.01.

3. Effect of composition extract on mice writhing pain caused by acetic acid:

Take Kunming mice and divide them into groups according to body weight. The administration groups were given extracts of different compositions. After the last administration, each mouse was intraperitoneally injected with 0.6% acetic acid solution 0.2ml/only, observed the number of writhing reactions (abdominal concave, stretched hind limbs, buttocks raised) within 15 minutes after the injection, and calculated the analgesic percentage. The results are shown in Table 4. Compared with the model group, the components of different parts, composition extracts and positive drug groups can significantly reduce the number of mice writhing caused by acetic acid to varying degrees.

The influence of table 4 composition extract on the mice writhing pain caused by acetic acid (X ± S)

Compared with the model group: ^* P＜0.05

4. Effect of composition extract on rat gastrointestinal dysfunction caused by reserpine:

Healthy adult male SD rats were divided into 6 groups. The normal control group was intraperitoneally injected with normal saline 5ml·kg ^-1 ·d ^-1 , and the rest of the groups were intraperitoneally injected with reserpine 0.5mg·kg ^-1 ·d ^-1 . Extracts of different compositions were administered to the normal control group and the model group by intragastric administration of equal volumes of distilled water, once·d ^-1 . During the administration process, the feces and signs of the rats were observed at any time, and the body weight and food intake of the rats were weighed every day. After 14 consecutive days, the following samples were collected according to the MTL radioimmunoassay kit: plasma, jejunum tissue. Immediately afterward, the thymus and spleen of each rat were taken out and weighed. The components and composition extracts of different parts were compared with the model group, and the inter-group t test was carried out. The results are shown in Table 5. After 14 days of continuous modeling with reserpine in rats, the body weight, food intake, thymus index, spleen index, Compared with the normal control group, the MTL levels in plasma and jejunum homogenate were significantly lower. Compared with the model group, the components of different parts, the body weight of the composition extract, the food intake, the thymus index, the MTL level in plasma and jejunal tissue homogenate were significantly different.

The influence (X ± S) of the composition extract of table 5 on the rat gastrointestinal dysfunction caused by reserpine

Compared with the control group: ^△ P<0.05, ^△△ P<0.01. Compared with the model group: *P<0.05, **P<0.01.

5. Effect of the composition extract on the damage of gastrointestinal mucosa:

Gastrointestinal tissues were collected, and the mucosal damage was observed with the naked eye, light microscope, and transmission electron microscope. The results are shown in Table 6.

Table 6 Observation of injury of gastrointestinal mucosa

Clinical use observation:

The present invention provides a compound composition of traditional Chinese medicine (including the above-mentioned, various combinations of extracts or chemical drugs) for IBS and other gastrointestinal disorders on the basis of traditional Chinese medicine theory and pharmacological experiments and clinical observation. Disease treatment, the effect is better. The result is as follows:

Choice of control drug:

In recent years, there have been many cases of clinical reports using Smecta to treat IBS to achieve good results. Smecta can improve various symptoms of IBS, especially in terms of stool frequency and stool properties. After taking the medicine, the symptoms can be quickly relieved and Improvement, most patients can return to normal stool after 3-4 days.

Case selection criteria:

Select 50 patients with irritable bowel syndrome with a course of more than 1 month, case selection: according to Rome criteria II selection. In all cases, organic diseases were excluded by blood routine, stool routine, liver function, blood sugar, B-ultrasound of liver, gallbladder and pancreas, fiber colonoscopy or intestinal barium contrast. The clinical manifestations are mainly diarrhea, accompanied by abdominal distension, borborygmus, abdominal pain, which can be relieved after defecation.

Healing:

Among the cases, there were 39 males and 31 females; they were divided into a treatment group of 50 cases and a control group of 20 cases. The two groups were similar in gender, age, and clinical manifestations and were comparable. Treatment group: with the prescription of the present invention, one dose per day. After 2 weeks of treatment, the symptoms improved twice a day, and then used for another 2 weeks. The clinical manifestations after 4 weeks were used as the basis for judging the curative effect. Control group: Smecta 3 grams once, 3 times a day, the course of treatment is the same as before. It is a non-random grouping. After 4 weeks of treatment, the blood routine and liver function will be checked. During the treatment, the patients will be followed up once a week to understand the changes in symptoms, the characteristics and frequency of defecation, and check the routine of stool.

Efficacy evaluation

Markedly effective: Diarrhea stopped, accompanied by obvious relief of symptoms. Effective: The diarrhea was obviously relieved, and the bowel movements were 2 times a day, accompanied by the improvement of the symptoms. Invalid: Does not meet the above criteria.

result observation

The prescription group of the present invention: 50 cases, 29 cases (58%) are markedly effective, 12 cases (24%) are effective, 9 cases (18%) are invalid, and the total effective rate is 82%. Of the 20 cases in the control group, 4 cases (20%) were markedly effective, 7 cases (35%) were effective, and 9 cases (45%) were ineffective, and the total effective rate was 55%. The curative effect of the prescription of the present invention is higher than that of Smecta, and the fastest onset of effect of self-prepared prescription treatment is 5 days. The curative effect was stable for 3 weeks, indicating that the symptoms of abdominal pain and discomfort were significantly reduced, and the intestinal function was improved (including the reduction of stool frequency and urgency, and the improvement of stool shape), and the symptom improvement appeared within the first four weeks of medication and was maintained throughout the medication period. Prolonging the course of treatment for ineffective cases could not improve the curative effect. No obvious adverse reactions were observed in the two groups of medications, and there was no change in blood routine and liver function after treatment.

Description of drawings

Figure 1 is a schematic diagram of the separation of different chemical sites;

Fig. 2 is a process flow chart of the present invention.

Detailed ways

Example 1, the prescription is: Bupleurum 6 grams, Radix Paeoniae Alba 6 grams, Radix Pseudostellariae 3 grams, Radix Glycyrrhizae 6 grams.

The above composition is extracted with water, ethanol, or other organic solvents;

Purification, separation and drying: the extract of water or ethanol is obtained by vacuum concentration, ethanol precipitation, resin adsorption, resin exchange, high-speed centrifugation, cyclodextrin inclusion and other methods;

Granules, capsules, tablets, preparations for transdermal or transmucosal administration, and suppositories for rectal administration prepared by adding appropriate pharmaceutical adjuvants to the above drugs.

Example 2 is basically the same as Example 1, but the prescription is: Bupleurum 18 grams, Radix Paeoniae Alba 30 grams, Radix Pseudostellariae 18 grams, Radix Glycyrrhizae 15 grams. At the same time, the preparation method is changed to:

The above composition is extracted with water, ethanol, or other organic solvents;

Purification, separation and drying: the extract of water or ethanol is obtained by vacuum concentration, ethanol precipitation, resin adsorption, resin exchange, high-speed centrifugation, cyclodextrin inclusion and other methods;

The above extracts are directly or purified and separated by adding appropriate pharmaceutical excipients to prepare granules, capsules, tablets, oral liquids, injections, transdermal or transmucosal administration preparations, and suppositories for rectal administration.

Example 3 is basically the same as Example 1 or 2, but the prescription is: Bupleurum 12 grams, Radix Paeoniae Alba 12 grams, Radix Pseudostellariae 6 grams, Radix Glycyrrhizae 6 grams.

Example 4 is basically the same as Example 1 or 2, but the prescription is: Bupleurum bupleuri 18 grams, Radix Paeoniae Alba 30 grams, Radix Pseudostellariae 12 grams, Radix Glycyrrhizae 12 grams.

Example 5 is basically the same as Example 1 or 2, but the prescription is: Bupleurum 9 grams, Radix Paeoniae Alba 9 grams, Radix Pseudostellariae 6 grams, Licorice 6 grams.

Example 6 is basically the same as Example 1 or 2, but the prescription is: Bupleurum 12 grams, Radix Paeoniae Alba 12 grams, Radix Pseudostellariae 12 grams, Radix Glycyrrhiza 12 grams.

Example 7 is basically the same as Example 1 or 2, but the prescription is: Bupleurum 9 grams, Radix Paeoniae Alba 9 grams, Radix Pseudostellariae 6 grams, Radix Glycyrrhizae 6 grams.

Example 8 is basically the same as Example 1 or 2, but the prescription is: Bupleurum 12 grams, Radix Paeoniae Alba 12 grams, Radix Pseudostellariae 6 grams, Radix Glycyrrhizae 6 grams.

Example 9 is basically the same as Example 1 or 2, but the prescription is: Bupleurum 15 grams, Radix Paeoniae Alba 18 grams, Radix Pseudostellariae 9 grams, Radix Glycyrrhizae 9 grams.

Example 10 is basically the same as Example 1 or 2, but the prescription is: Bupleurum 12 grams, Radix Paeoniae Alba 27 grams, Radix Pseudostellariae 6 grams, Radix Glycyrrhizae 9 grams.

Example 11 is basically the same as Example 1 or 2, but the prescription is: Bupleurum 12 grams, Radix Paeoniae Alba 12 grams, Radix Pseudostellariae 6 grams, Atractylodes Rhizome 9 grams, Radix Glycyrrhizae 6 grams.

Example 12 is basically the same as Example 1 or 2, but the prescription is: Bupleuri 9 grams, Radix Paeoniae Alba 9 grams, Rhizoma Chuanxiong 6 grams, Radix Pseudostellariae 6 grams, Radix Glycyrrhizae 6 grams.

Example 13 is basically the same as Example 1 or 2, but the prescription is: Bupleurum 9 grams, Radix Paeoniae Alba 18 grams, Radix Pseudostellariae 6 grams, Radix Glycyrrhizae 9 grams, Chenpi 9 grams.

Example 14 is basically the same as Example 1 or 2, but the prescription is: Bupleurum bupleuri 9 grams, Radix Paeoniae Alba 9 grams, Radix Pseudostellariae 6 grams, Licorice 6 grams, Citrus aurantium 9 grams.

Example 15 is basically the same as Example 1 or 2, but the prescription is: Bupleurum 9 grams, Radix Paeoniae Alba 9 grams, Radix Pseudostellariae 6 grams, Radix Glycyrrhizae 6 grams, Scutellaria baicalensis 9 grams.

Example 16 is basically the same as Example 1 or 2, but the prescription is: Bupleurum 9 grams, Radix Paeoniae Alba 12 grams, Radix Pseudostellariae 6 grams, Licorice 6 grams, Chenpi 6-9 grams, Fangfeng 6-9 grams.

Example 17 is basically the same as Example 1 or 2, but the prescription is: Bupleurum 9 grams, Radix Paeoniae Alba 9 grams, Radix Pseudostellariae 6 grams, Radix Glycyrrhizae 6 grams, Atractylodes Rhizome 9 grams, Fangfeng 6-9 grams.

Example 18 is basically the same as Example 1 or 2, but the prescription is: Bupleurum 9 grams, Radix Paeoniae Alba 9 grams, Radix Pseudostellariae 6 grams, Radix Glycyrrhizae 6 grams, Atractylodes Rhizome 9 grams, Coptidis 6-9 grams.

Example 19 is basically the same as Example 1 or 2, but the prescription is: Bupleurum 9 grams, Radix Paeoniae Alba 9 grams, Radix Pseudostellariae 6 grams, Radix Glycyrrhizae 6 grams, Atractylodes macrocephala 9 grams, Poria cocos 9 grams.

Example 20 is basically the same as Example 1 or 2, but the prescription is: Bupleurum 9 grams, Radix Paeoniae Alba 9 grams, Radix Pseudostellariae 6 grams, Radix Glycyrrhiza 6 grams, Cortex Albiziae Julibrissin 9 grams,

Example 21 is basically the same as Example 1 or 2, but the prescription is: Bupleurum 9 grams, Radix Paeoniae Alba 9 grams, Radix Pseudostellariae 6 grams, Radix Glycyrrhizae 6 grams, Citrus aurantium 6 grams.

Example 22 is basically the same as Example 1 or 2, but the prescription is: Bupleurum 9 grams, Radix Paeoniae Alba 9 grams, Radix Pseudostellariae 6 grams, Licorice 6 grams, Poria cocos 9 grams, Atractylodes macrocephala 9 grams.

Example 23 is basically the same as Example 1 or 2, but the prescription is: Bupleurum 9 grams, Radix Paeoniae Alba 9 grams, Radix Pseudostellariae 6 grams, Licorice 6 grams, Rhizoma Chuanxiong 6 grams.

Example 24 is basically the same as Example 1 or 2, but the prescription is: Bupleurum bupleurum 9 grams, Radix Paeoniae Alba 9 grams, Radix Pseudostellariae 6 grams, Atractylodes macrocephala 9 grams, licorice 6 grams, Citrus aurantium 6 grams.

Example 25 is basically the same as Example 1 or 2, but the prescription is: Bupleurum 9 grams, Radix Paeoniae Alba 9 grams, Radix Pseudostellariae 6 grams, Radix Glycyrrhizae 6 grams, Atractylodes Rhizome 9 grams, Coptidis 6-9 grams.

Example 26 is basically the same as Example 1 or 2, but the prescription is: Bupleurum 9 grams, Radix Paeoniae Alba 9 grams, Radix Pseudostellariae 6 grams, Licorice 6 grams, Tangerine Peel 6 grams, Citrus Citrifolia 6 grams.

Example 27 is basically the same as Example 1 or 2, but the prescription is: Bupleurum 9 grams, Radix Paeoniae Alba 9 grams, Radix Pseudostellariae 6 grams, Atractylodes Rhizome 9 grams, Licorice 6 grams, Coptidis 6 grams, and Chenpi 6 grams.

Example 28 is basically the same as Example 1 or 2, but the prescription is: Bupleurum 9 grams, Radix Paeoniae Alba 9 grams, Radix Pseudostellariae 6 grams, Atractylodes Rhizome 9 grams, Licorice 6 grams, Fangfeng 9 grams.

Example 29 is basically the same as Example 1 or 2, but the prescription is: Bupleurum 9 grams, Radix Paeoniae Alba 9 grams, Radix Pseudostellariae 6 grams, Atractylodes Rhizome 9 grams, Licorice 6 grams, Rhizoma Chuanxiong 6 grams.

Example 30 is basically the same as Example 1 or 2, but the prescription is: Bupleurum 9 grams, Radix Paeoniae Alba 9 grams, Radix Pseudostellariae 6 grams, Atractylodes Rhizoma Atractylodes Rhizome 9 grams, Licorice 6 grams, Angelica sinensis, Coptidis 3 grams.

Example 31 is basically the same as Example 1 or 2, but the prescription is: 9 grams of Atractylodes macrocephala, 9 grams of Poria cocos, 6 grams of licorice, 6 grams of Bupleurum, 6 grams of Radix Pseudostellariae, 12 grams of Radix Paeoniae Alba, and 9 grams of Scutellaria baicalensis.

Example 32 is basically the same as Example 1 or 2, but the prescription is: Bupleurum 9 grams, Radix Paeoniae Alba 9 grams, Radix Pseudostellariae 6 grams, Atractylodes Rhizome 9 grams, and Radix Glycyrrhizae 6 grams.

Example 33 is basically the same as Example 1 or 2, but the prescription is: Bupleuri 9 grams, Radix Paeoniae Alba 9 grams, Radix Pseudostellariae 6 grams, Atractylodes macrocephala 9 grams, Licorice 6 grams, Rhizoma Chuanxiong 6 grams, Poria cocos 9 grams.

Example 34 is basically the same as Example 1 or 2, but the prescription is: Bupleurum 9 grams, Radix Paeoniae Alba 9 grams, Radix Pseudostellariae 6 grams, Radix Glycyrrhizae 6 grams.

With reference to Fig. 1, Fig. 2: adopt water, ethanol or other organic solvent extraction to above-mentioned composition;

Purification, separation and drying: water extract, vacuum concentration, ethanol precipitation, resin adsorption, resin exchange, high-speed centrifugation, spray drying, vacuum drying, cyclodextrin inclusion and other methods to obtain the extract;

The composition obtained by water or ethanol extract of 9 grams of Atractylodes macrocephala, 6 grams of Rhizoma Chuanxiong and 9 grams of Poria cocos is added.

Granules, capsules, tablets, preparations for transdermal or transmucosal administration, and suppositories for rectal administration prepared by adding appropriate pharmaceutical adjuvants to the above drugs.

Example 35 is basically the same as Example 34, but a composition obtained by adding 9 grams of Atractylodes macrocephala and 9 grams of Citrus aurantium in water or an extract.

Example 36 is basically the same as Example 34, but the composition obtained by adding water or extracts of 9 grams of Fangfeng and 9 grams of dried orange peel.

Example 37 is basically the same as Example 34, but the water extracts of Coptidis Rhizoma and Fructus Citrus Fructus are added.

Example 38 is basically the same as Example 34, but adding 9 grams of Atractylodes Rhizome and 6-9 grams of n-butanol extract of Fangfeng.

Example 40, which is substantially the same as Example 34, but with the addition of 6 grams of ethyl acetate extract from Fructus Aurantii.

Example 41 is substantially the same as Example 34, but adding 6 grams of tangerine peel and 6 grams of water extract of Citrus aurantium.

Example 42 is basically the same as Example 34, but adding 9 grams of Atractylodes macrocephala and 6 grams of Rhizoma Chuanxiong water extract.

Embodiment 43 is substantially the same as Embodiment 1 or 2. 9 grams of Bupleurum, 9 grams of white peony root, 6 grams of heterophylla, and 6 grams of licorice. The above composition is extracted with water, ethanol, or other organic solvents;

Purification, separation and drying: water extract, vacuum concentration, ethanol precipitation, resin adsorption, resin exchange, high-speed centrifugation, spraying Extracts obtained by methods such as fog drying, vacuum drying, and cyclodextrin inclusion;

Add Alosetron (Alosetron) 0.5-3mg,

Granules, capsules, tablets, preparations for transdermal or transmucosal administration, and suppositories for rectal administration prepared by adding appropriate pharmaceutical adjuvants to the above drugs.

Example 44 is basically the same as Example 43, but the alosetron is changed to 5-20 mg of domperidone.

Example 45 is basically the same as Example 43, except that alosetron is changed to cisapride (cisapride) 1-20 mg.

Example 46 is basically the same as Example 43, except that alosetron is changed to 2-15 mg of Tegaserod.

Example 47 is basically the same as Example 43, except that alosetron is changed to otilonium bromide (Spasmomen) 50-200 mg.

Example 48 is basically the same as Example 43, except that alosetron is changed to 50-200 mg of pinaverum bromide.

Example 49 is basically the same as Example 43, except that alosetron is changed to trimebutine maleate (Trimebutine) 0.2-1.5 g.

Example 50 is basically the same as Example 43, except that alosetron is changed to 40-200 mg of butyric acid bacteria.

Example 51, 9 grams of Radix Bupleurum, 9 grams of Radix Paeoniae Alba, 6 grams of Radix Pseudostellariae, 6 grams of Radix Glycyrrhizae, 9 grams of Atractylodes Rhizoma Rhizome, after crushing, 54,000 grams, ten times the amount of water, extracted twice at 100°C for one hour each time, combined The extract was concentrated under reduced pressure (50°C, 0.1M) to a relative density of 1.07, and 95% ethanol was added to make the solution alcohol content 50%, and stored at 4°C for 24 hours. Take the supernatant and spray dry it, the total solid is 8100g, to prepare various solid preparations; or take the supernatant to prepare liquid preparations.

Example 52, 9 grams of Radix Bupleuri, 9 grams of Radix Paeoniae Alba, 6 grams of Radix Pseudostellariae, 6 grams of Radix Glycyrrhizae, and 9 grams of Atractylodes Rhizoma Rhizoma Rhizome, were crushed, extracted twice at 100°C with 54,000 grams of ten times water, each time for one hour, and combined extraction After passing through an anion exchange resin column (weak base type) and a cation exchange resin column (strong acid type) successively, they were eluted with PH5.5 acetate buffer solution and pH9.0 ammonia water buffer solution respectively, and the eluate was concentrated under reduced pressure ( 50°C, -0.1M), after vacuum drying, 1610 grams of total solids were obtained to prepare various solid preparations; or take the concentrated solution to prepare liquid preparations.

Example 53: 9 grams of Radix Bupleurum, 9 grams of Radix Paeoniae Alba, 6 grams of Radix Pseudostellariae, 6 grams of Radix Glycyrrhizae, and 9 grams of Atractylodes Rhizoma Atractylodes Rhizome are crushed, extracted twice at 100°C with 54,000 grams of water, each time 10 times of water, for one hour, and combined the extracts , after successively passing through the macroporous exchange resin column (AB-8), and eluting with 20%, 40%, 60%, and 95% ethanol solution respectively, the eluate was concentrated under reduced pressure (50°C, -0.1Mpa), The total solid after vacuum drying is 1730 grams, and various solid preparations are prepared; or the concentrated solution is used to prepare liquid preparations.

Example 54: 9 grams of Radix Bupleuri, 9 grams of Radix Paeoniae Alba, 6 grams of Radix Pseudostellariae, 6 grams of Radix Glycyrrhizae, and 9 grams of Atractylodes Rhizoma Rhizoma Rhizome, were crushed, extracted twice at 100°C with 54,000 grams of water, each time 10 times of water, for one hour, and combined the extracts , concentrated under reduced pressure (50°C, -0.1Mpa) to a relative density of 1.07-1.10, centrifuged at 4000-20000rpm for 20min, and the supernatant was spray-dried to obtain a total solid of 10220 grams, and various solid preparations were prepared; or the supernatant was prepared liquid formulations.

Example 55, referring to Figure 1 and Figure 2: 9 grams of Bupleurum Radix, 9 grams of Radix Paeoniae Alba, 6 grams of Radix Pseudostellariae, 6 grams of Radix Glycyrrhizae, and 9 grams of Atractylodes Rhizoma Atractylodes Rhizoma Rhizoma Rhizome. , one hour, combine the extracts, concentrate under reduced pressure (50°C, -0.1Mpa) to a relative density of 1.07-1.10, 4000-20000rpm, 20min, take the supernatant and pass it through a 50000M or 10000M ultrafiltration membrane. Concentrate the ultrafiltrate under reduced pressure (50°C, -0.1Mpa), spray-dry to obtain 7030 g of total solids to prepare various solid preparations; or take the ultrafiltrate to prepare injections.

Example 56: 9 grams of Radix Bupleuri, 9 grams of Radix Paeoniae Alba, 6 grams of Radix Pseudostellariae, 6 grams of Radix Glycyrrhizae, and 9 grams of Atractylodes Rhizoma Atractylodes Rhizome are crushed, extracted twice at 100°C with 54,000 grams of water, each time ten times water, for one hour, and the extracts were combined , concentrated under reduced pressure (50°C, -0.1Mpa) to a relatively dense Degree 1.35-1.40, add a small amount of silica gel to mix, use silica gel column, 20%, 40%, 60%, 95% ethanol solution for segmental elution, and the eluent of each segment is concentrated under reduced pressure (50°C, -0.1Mpa) After vacuum drying, 130 grams, 320 grams, 570 grams, and 598 grams of solid matter were obtained respectively to prepare various solid preparations; or take the concentrated solution to prepare liquid preparations.

Example 57: 9 grams of Radix Bupleurum, 9 grams of Radix Paeoniae Alba, 6 grams of Radix Pseudostellariae, 6 grams of Radix Glycyrrhizae, and 54,000 grams of Atractylodes Rhizoma Rhizome were crushed into coarse particles, then ten times of water was added, extracted by steam distillation for 5 hours, and the distillate was collected. Merge, add salt to the distillate to make it saturated, leave it for 24 hours, separate 25 grams of oil, add 200 grams of β-cyclodextrin, and process it with a colloid mill for 30 minutes. Vacuum dried (50°C, -0.1Mpa). Obtain 206 grams of white solids, and prepare various solid preparations.

Example 58, using the basic formula as the raw material, taking the extract E and its components as medicine: the Chinese medicine compound composition is extracted with water, after being properly concentrated, ethanol of different concentrations is added, left to stand and then centrifuged, and the supernatant is concentrated, get. Analysis by HPLC, TLC, IR, NHR, MS, UV, etc. mainly contains component combinations 2, 3, 4, 5, and 6. The total solid yield is 14-18% of the medicinal material weight.

Example 59, using the basic formula as the raw material, taking the extract S and its components as medicine: the Chinese medicine compound composition is extracted with water, after being properly concentrated, multiple combinations of components with different polarities are respectively obtained by silica gel column chromatography , and analyzed by HPLC, TLC, IR, NHR, MS, UV, etc., are component combinations 2, 3, 4, 5, 6, and 7, respectively.

Example 60, using the basic formula as the raw material, taking the extract L and its components as medicine: the Chinese medicine compound composition is extracted with water, and exchanged and adsorbed by an ion exchange column to obtain multiple different component combinations. Analysis by HPLC, TLC, IR, NHR, MS, UV, etc., which are component combinations 2, 3, 4, and 5, respectively.

Example 61, using the basic formula as the raw material, taking the extract G and its components as medicine: the Chinese medicine compound composition is extracted with water, after being properly concentrated, and subjected to high-speed centrifugation, the components are soluble in aqueous solution. A number of different ingredient combinations are obtained. Analysis by HPLC, TLC, IR, NHR, MS, UV, etc., which are component combinations 2, 3, 4, and 5, respectively. The total solid yield is 18-24% of the medicinal material weight.

Example 62, using the basic formula as the raw material, taking the extract D and its components as medicine: the Chinese medicine compound composition is extracted with water, adsorbed by a macroporous adsorption resin and then eluted to obtain multiple different component combinations. Analyzed by HPLC, TLC, IR, NHR, MS, UV, etc., which are component combinations 2, 3, 4, 5, 6, and 7, respectively. The solid yield is 2.0-7.0% of the medicinal material weight.

Example 63, using the basic formula as the raw material, extract C and its components as medicine: the traditional Chinese medicine compound composition is extracted with water, concentrated properly, subjected to high-speed centrifugation, and treated with ultrafiltration to obtain different composition combinations, which are analyzed by HPLC and TLC , IR, NHR, MS, UV and other analysis, which are component combinations 2, 3, 4, 5, 6, and 7 respectively. The total solid yield is 10-15% of the medicinal material weight.

Claims (4)

1. a Chinese medicine composition for the treatment of bowel dysfunction is characterized in that, crude drug composed as follows:

Radix Bupleuri 6-18 gram,

Radix Paeoniae Alba 6-30 gram,

Radix Pseudostellariae 6-18 gram,

Radix Glycyrrhizae 6-15 gram.

2. according to the Chinese medicine composition of the described treatment bowel dysfunction of claim 1, it is characterized in that: the proportioning of each crude drug is:

Radix Bupleuri 12-18 gram,

Radix Paeoniae Alba 12-30 gram,

Radix Pseudostellariae 6-12 gram,

Radix Glycyrrhizae 6-12 gram.

3. according to the Chinese medicine composition of the described treatment bowel dysfunction of claim 1, it is characterized in that: the proportioning of each crude drug is:

Radix Bupleuri 9-12 gram,

Radix Paeoniae Alba 9-12 gram,

Radix Pseudostellariae 6-12 gram,

Radix Glycyrrhizae 6-12 gram.

4. according to the Chinese medicine composition of claim 2 or 3 described treatment bowel dysfunctions, it is characterized in that: said Chinese medicine composition is that a kind of extraction in by the following method obtains:

Water extraction is adopted in the combination of crude drug, after suitably concentrating, after high speed centrifugation is handled, gets water-soluble component; Or

Water extraction is adopted in the combination of crude drug, after suitably concentrating, and the extract that after high speed centrifugation, hyperfiltration treatment, obtains.

Images