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CN114073731A - A Chinese medicinal composition for treating abdominal pain and diarrhea - Google Patents

A Chinese medicinal composition for treating abdominal pain and diarrhea Download PDF

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Publication number
CN114073731A
CN114073731A CN202010815618.9A CN202010815618A CN114073731A CN 114073731 A CN114073731 A CN 114073731A CN 202010815618 A CN202010815618 A CN 202010815618A CN 114073731 A CN114073731 A CN 114073731A
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diarrhea
radix
fructus aurantii
traditional chinese
chinese medicine
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张贵民
程国良
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Lunan Pharmaceutical Group Corp
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Lunan Pharmaceutical Group Corp
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/23Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/237Notopterygium
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    • A61K36/06Fungi, e.g. yeasts
    • A61K36/07Basidiomycota, e.g. Cryptococcus
    • A61K36/076Poria
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/23Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
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    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/23Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/236Ligusticum (licorice-root)
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
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    • A61K36/185Magnoliopsida (dicotyledons)
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    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/48Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/484Glycyrrhiza (licorice)
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    • A61K36/185Magnoliopsida (dicotyledons)
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    • A61K2236/30Extraction of the material
    • A61K2236/33Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/333Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH

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Abstract

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating abdominal pain and diarrhea. The traditional Chinese medicine composition is mainly prepared from notopterygium root, radix angelicae pubescentis, poria cocos, divaricate saposhnikovia root, schizonepeta, ligusticum wallichii, platycodon grandiflorum, radix bupleuri, radix peucedani, fructus aurantii and liquorice. The traditional Chinese medicine composition can reduce gastrointestinal tract viscera sensitivity, regulate neurotransmitter excitability, reduce the release of pain substances, improve intestinal inflammation and also has the effect of strengthening spleen.

Description

A Chinese medicinal composition for treating abdominal pain and diarrhea
Technical Field
The invention relates to a composition, in particular to a traditional Chinese medicine composition for treating and/or relieving abdominal pain and diarrhea, and belongs to the technical field of traditional Chinese medicines.
Background
Diarrhea (diarrhea) is commonly called "diarrhea," and refers to the change in defecation habits and stool characteristics. It is manifested as increased frequency of defecation, increased stool volume, unformed, loose or liquid stool, sometimes with purulent blood or with undigested material and fat. It is divided into acute and chronic types according to the course of disease and the degree of urgency and severity of disease. The cause of diarrhea is many, and not only the disease of the intestinal tract itself but also the disease or injury outside or systemic intestine can cause diarrhea. The typical clinical manifestations of diarrhea are mainly: (1) the defecation frequency is changed, which is shown in that the defecation frequency is increased, and acute diarrhea is defecated for several times or even dozens of times every day; (2) the nature of the excrement is changed, the excrement is thin or is water-like, and mucus and purulent blood can be brought in the excrement; (3) abdominal pain, acute diarrhea often has abdominal pain, and especially infectious diarrhea is more obvious. Diarrhea and pain of small intestine diseases are usually around umbilicus, and abdominal pain is not obviously relieved after defecation. Pain caused by colon diseases is mostly in the lower abdomen, and pain after defecation can be relieved; (4) tenesmus, i.e. feeling of anal distention, frequent defecation and incomplete defecation; (5) otherwise, some patients may have alternating diarrhea and constipation, vomiting, etc.
The term "abdominal pain" refers to the pain occurring in the area below the gastric cavity and above the pubic hairline. The abdominal pain is mainly caused by qi stagnation, obstruction of collaterals or malnutrition of the meridians and unsmooth circulation of qi and blood due to exogenous seasonal pathogens, improper diet, emotional disorders and constitutional yang deficiency. Abdominal pain (abdominal pain) is a common clinical symptom, and is usually caused by pathological changes of organs in abdominal cavity, chest diseases and systemic diseases. Abdominal pain can be divided into acute and chronic abdominal pain. Acute abdominal pain is acute and the course of disease is short; the chronic abdominal pain has a slow onset and a long course. In clinic, the location of abdominal pain, nature of pain, onset urgency, duration, and accompanying symptoms should be analyzed.
Abdominal pain is caused by various gastrointestinal diseases, such as dysentery and acute gastritis in acute gastrointestinal diseases, ulcer, gastric cancer, pancreatitis, cholecystitis, irritable bowel syndrome and the like in chronic gastrointestinal diseases, so that the abdominal pain is one of the most common symptoms of gastrointestinal diseases and is an important signal for gastrointestinal diseases.
Disclosure of Invention
The inventor explains that the invention is further developed on the basis of the existing product 'Jingfang granules', and the new application of the Jingfang granules comes from clinical use feedback. Part of patients with cold due to wind-cold type of digestive tract diseases feedback that symptoms such as abdominal pain and diarrhea caused by the digestive tract diseases are also improved during taking Jingfang granules.
Based on the clinical use feedback, the inventor further researches and develops the new application of the Jingfang granules and the prescription thereof in treating and/or improving the abdominal pain and diarrhea.
One of the purposes of the invention is to provide a traditional Chinese medicine composition for treating and/or improving abdominal pain and diarrhea, which is mainly prepared from notopterygium root, radix angelicae pubescentis, poria cocos, radix sileris, schizonepeta, ligusticum wallichii, platycodon grandiflorum, radix bupleuri, radix peucedani, fructus aurantii and liquorice.
The diarrhea of the invention mainly comprises infectious diarrhea and non-infectious diarrhea.
Preferably, the infectious diarrhea mainly refers to diarrhea caused by infection with one or more of bacteria, viruses, fungi and parasites; further preferably, the bacteria may be diarrhea causing escherichia coli, campylobacter jejuni, etc., the viruses may be rotavirus, norovirus, etc., the parasites may be giardia lamblia, amoeba, etc., and the fungal infection may be candida, aspergillus, mucor, etc.
Preferably, the non-infectious diarrhea is diarrhea caused by one or more of dietary factors, pharmaceutical factors, climatic factors, and disease factors.
Further preferably, the disease factors may be gastric diseases, intestinal diseases, pancreatic diseases, liver and gall diseases; the abdominal pain mainly refers to the abdominal pain caused by digestive tract diseases; or abdominal pain associated with acute diarrhea.
The second purpose of the present invention is to provide the specific composition of the above traditional Chinese medicine composition, namely, the traditional Chinese medicine composition is mainly prepared from the following raw materials:
Figure BDA0002632554500000021
preferably, the traditional Chinese medicine composition is mainly prepared from the following raw materials:
Figure BDA0002632554500000022
further preferably, the traditional Chinese medicine composition is mainly prepared from the following raw materials:
Figure BDA0002632554500000023
Figure BDA0002632554500000031
the invention also aims to provide a preparation method of the traditional Chinese medicine composition, which mainly comprises the following steps:
step A: distilling herba Schizonepetae, radix Saposhnikoviae, Notopterygii rhizoma, radix Angelicae Pubescentis, radix Peucedani, rhizoma Ligustici Chuanxiong, and fructus Aurantii to obtain volatile oil, and collecting the residue, rhizoma Ligustici Chuanxiong, and fructus Aurantii water solution;
and B: b, preparing the distilled water solution of the ligusticum wallichii and the fructus aurantii obtained in the step A into a 10-40% ethanol solution for later use;
and C: mixing Poria, the distilled rhizoma Ligustici Chuanxiong obtained in step A, and fructus Aurantii residue, percolating with the ethanol solution obtained in step B, and collecting percolate;
step D: decocting radix bupleuri, platycodon grandiflorum, liquorice, the distilled schizonepeta obtained in the step A, divaricate saposhnikovia root, notopterygium root, radix angelicae pubescentis and radix peucedani dregs in water, and concentrating the decoction for later use;
step E: and D, mixing the percolate obtained in the step C and the decoction obtained in the step D, concentrating, and adding the volatile oil obtained in the step A to obtain the composition.
Preferably, the preparation method mainly comprises the following steps:
step A: distilling herba Schizonepetae, radix Saposhnikoviae, Notopterygii rhizoma, radix Angelicae Pubescentis, radix Peucedani, rhizoma Ligustici Chuanxiong, and fructus Aurantii to obtain volatile oil, and collecting the residue, rhizoma Ligustici Chuanxiong, and fructus Aurantii water solution;
and B: b, preparing the distilled water solution of the ligusticum wallichii and the fructus aurantii obtained in the step A into 15-30% ethanol solution for later use;
and C: mixing Poria, the distilled rhizoma Ligustici Chuanxiong obtained in step A, and fructus Aurantii residue, percolating with the ethanol solution obtained in step B, and collecting percolate;
step D: decocting radix bupleuri, platycodon grandiflorum, liquorice, the distilled schizonepeta obtained in the step A, divaricate saposhnikovia root, notopterygium root, radix angelicae pubescentis and radix peucedani dregs in water, and concentrating the decoction into thick paste for later use;
step E: and D, mixing the percolate obtained in the step C and the thick paste obtained in the step D, concentrating the mixture into clear paste, and adding the volatile oil obtained in the step A to obtain the ointment.
Further preferably, the preparation method mainly comprises the following steps:
step A: distilling herba Schizonepetae, radix Saposhnikoviae, Notopterygii rhizoma, radix Angelicae Pubescentis, radix Peucedani, rhizoma Ligustici Chuanxiong, and fructus Aurantii to obtain volatile oil, and collecting the residue, rhizoma Ligustici Chuanxiong, and fructus Aurantii water solution;
and B: b, preparing the distilled water solution of the ligusticum wallichii and the fructus aurantii obtained in the step A into a 25% ethanol solution for later use;
and C: mixing Poria, the distilled rhizoma Ligustici Chuanxiong obtained in step A, and fructus Aurantii residue, percolating with the ethanol solution obtained in step B, and collecting percolate;
step D: decocting radix bupleuri, platycodon grandiflorum, liquorice, the distilled schizonepeta obtained in the step A, divaricate saposhnikovia root, notopterygium root, radix angelicae pubescentis and radix peucedani dregs in water, and concentrating the decoction into thick paste for later use;
step E: and D, mixing the percolate obtained in the step C and the thick paste obtained in the step D, concentrating the mixture into clear paste, and adding the volatile oil obtained in the step A to obtain the ointment.
The fourth purpose of the invention is to provide a traditional Chinese medicine preparation, which contains the traditional Chinese medicine composition and pharmaceutically acceptable auxiliary materials, and the traditional Chinese medicine preparation can be a clinically acceptable oral preparation;
preferably, the clinically acceptable oral preparation is one or more of pills, capsules, tablets, granules or liquid oral preparations;
even more preferably, the oral formulation is a granule.
The invention also provides application of the Jingfang granules in preparing medicaments for treating and/or improving abdominal pain and diarrhea.
Compared with the prior art, the invention has the following remarkable technical effects:
1. the traditional Chinese medicine composition can reduce the AWR score of rats when CRD pressure is 20mmHg, 30mmHg and 40mmHg, and reduce gastrointestinal tract visceral sensitivity; it also can regulate the excitability of the neurotransmitters 5-HT and SP, reduce the release of the pain-causing substance SP, and stimulate cholinergic neurons.
2. The traditional Chinese medicine composition can improve the content of motilin and gastrin of diarrhea rats, can reduce the content of inflammatory factors, and can improve the content of inflammation-inhibiting factors.
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION
EXAMPLE 1 preparation of granules
Prescription:
Figure BDA0002632554500000041
the preparation method comprises the following steps:
step A: respectively distilling herba Schizonepetae, radix Saposhnikoviae, Notopterygii rhizoma, radix Angelicae Pubescentis, radix Peucedani, rhizoma Ligustici Chuanxiong, and fructus Aurantii to obtain volatile oil, and respectively distilling the residue, rhizoma Ligustici Chuanxiong, and fructus Aurantii to obtain water solution;
and B: b, preparing the distilled water solution of the ligusticum wallichii and the fructus aurantii obtained in the step A into a 25% ethanol solution for later use;
and C: mixing Poria, the distilled rhizoma Ligustici Chuanxiong obtained in step A, and fructus Aurantii residue, percolating with the ethanol solution obtained in step B, and collecting percolate;
step D: decocting radix bupleuri, platycodon grandiflorum, liquorice, the distilled schizonepeta obtained in the step A, divaricate saposhnikovia root, notopterygium root, radix angelicae pubescentis and radix peucedani dregs with water twice, each time for 1.5 hours, combining decoctions obtained in the two times, filtering and concentrating into thick paste for later use;
step E: and D, mixing the percolate obtained in the step C and the thick paste obtained in the step D, standing, filtering, concentrating into clear paste, adding a proper amount of cane sugar, uniformly mixing, preparing into granules, drying, adding the volatile oil obtained in the step A, and uniformly mixing to obtain the traditional Chinese medicine.
Example 2 preparation of granules
Prescription:
Figure BDA0002632554500000051
the preparation method is the same as example 1.
Example 3 oral liquid preparation
Prescription:
Figure BDA0002632554500000052
the preparation method comprises the following steps:
step A: respectively distilling herba Schizonepetae, radix Saposhnikoviae, Notopterygii rhizoma, radix Angelicae Pubescentis, radix Peucedani, rhizoma Ligustici Chuanxiong, and fructus Aurantii to obtain volatile oil, and respectively distilling the residue, rhizoma Ligustici Chuanxiong, and fructus Aurantii to obtain water solution;
and B: b, preparing the distilled water solution of the ligusticum wallichii and the fructus aurantii obtained in the step A into a 10% ethanol solution for later use;
and C: mixing Poria, the distilled rhizoma Ligustici Chuanxiong obtained in step A, and fructus Aurantii residue, percolating with the ethanol solution obtained in step B, and collecting percolate;
step D: decocting radix bupleuri, platycodon grandiflorum, liquorice, the distilled schizonepeta obtained in the step A, divaricate saposhnikovia root, notopterygium root, radix angelicae pubescentis and radix peucedani dregs with water twice, each time for 1.5 hours, combining decoctions obtained in the two times, filtering and concentrating into thick paste for later use;
step E: and D, mixing the percolate obtained in the step C and the thick paste obtained in the step D, standing, filtering, concentrating into clear paste, adding a proper amount of sucrose, mixing uniformly, adding the volatile oil obtained in the step A, mixing uniformly, and adding water to 1000ml to obtain the traditional Chinese medicine composition.
Example 4 syrup preparation
Prescription:
Figure BDA0002632554500000053
the preparation method comprises the following steps:
step A: respectively distilling herba Schizonepetae, radix Saposhnikoviae, Notopterygii rhizoma, radix Angelicae Pubescentis, radix Peucedani, rhizoma Ligustici Chuanxiong, and fructus Aurantii to obtain volatile oil, and respectively distilling the residue, rhizoma Ligustici Chuanxiong, and fructus Aurantii to obtain water solution;
and B: b, preparing the distilled water solution of the ligusticum wallichii and the fructus aurantii obtained in the step A into a 40% ethanol solution for later use;
and C: mixing Poria, the distilled rhizoma Ligustici Chuanxiong obtained in step A, and fructus Aurantii residue, percolating with the ethanol solution obtained in step B, and collecting percolate;
step D: decocting radix bupleuri, platycodon grandiflorum, liquorice, the distilled schizonepeta obtained in the step A, divaricate saposhnikovia root, notopterygium root, radix angelicae pubescentis and radix peucedani dregs with water twice, each time for 1.5 hours, combining decoctions obtained in the two times, filtering and concentrating into thick paste for later use;
step E: and D, mixing the percolate obtained in the step C and the thick paste obtained in the step D, standing, filtering, concentrating into clear paste, adding a proper amount of cane sugar, mixing uniformly, adding 500ml of the volatile oil and the simple syrup obtained in the step A, mixing uniformly, standing, filtering, and adding water to 1000ml to obtain the traditional Chinese medicine.
EXAMPLE 5 tablet preparation
Prescription:
Figure BDA0002632554500000061
the preparation method comprises the following steps:
step A: respectively distilling herba Schizonepetae, radix Saposhnikoviae, Notopterygii rhizoma, radix Angelicae Pubescentis, radix Peucedani, rhizoma Ligustici Chuanxiong, and fructus Aurantii to obtain volatile oil, and respectively distilling the residue, rhizoma Ligustici Chuanxiong, and fructus Aurantii to obtain water solution;
and B: b, preparing the distilled water solution of the ligusticum wallichii and the fructus aurantii obtained in the step A into a 15% ethanol solution for later use;
and C: mixing Poria, the distilled rhizoma Ligustici Chuanxiong obtained in step A, and fructus Aurantii residue, percolating with the ethanol solution obtained in step B, and collecting percolate;
step D: decocting radix bupleuri, platycodon grandiflorum, liquorice, the distilled schizonepeta obtained in the step A, divaricate saposhnikovia root, notopterygium root, radix angelicae pubescentis and radix peucedani dregs with water twice, each time for 1.5 hours, combining decoctions obtained in the two times, filtering and concentrating into thick paste for later use;
step E: and D, mixing the percolate obtained in the step C and the thick paste obtained in the step D, standing, filtering, concentrating into clear paste, adding a proper amount of cane sugar, uniformly mixing, granulating, drying, adding the volatile oil obtained in the step A, uniformly mixing, granulating, adding a proper amount of auxiliary materials, uniformly mixing, and tabletting to obtain the traditional Chinese medicine.
EXAMPLE 6 Capsule preparation
Prescription:
Figure BDA0002632554500000062
step A: respectively distilling herba Schizonepetae, radix Saposhnikoviae, Notopterygii rhizoma, radix Angelicae Pubescentis, radix Peucedani, rhizoma Ligustici Chuanxiong, and fructus Aurantii to obtain volatile oil, and respectively distilling the residue, rhizoma Ligustici Chuanxiong, and fructus Aurantii to obtain water solution;
and B: b, preparing the distilled water solution of the ligusticum wallichii and the fructus aurantii obtained in the step A into a 30% ethanol solution for later use;
and C: mixing Poria, the distilled rhizoma Ligustici Chuanxiong obtained in step A, and fructus Aurantii residue, percolating with the ethanol solution obtained in step B, and collecting percolate;
step D: decocting radix bupleuri, platycodon grandiflorum, liquorice, the distilled schizonepeta obtained in the step A, divaricate saposhnikovia root, notopterygium root, radix angelicae pubescentis and radix peucedani dregs with water twice, each time for 1.5 hours, combining decoctions obtained in the two times, filtering and concentrating into thick paste for later use;
step E: and D, mixing the percolate obtained in the step C and the thick paste obtained in the step D, standing, filtering, concentrating into clear paste, adding a proper amount of cane sugar, uniformly mixing, granulating, drying, adding the volatile oil obtained in the step A, uniformly mixing, granulating, drying, crushing and encapsulating to obtain the capsule.
EXAMPLE 7 pellet preparation
Prescription:
Figure BDA0002632554500000071
the preparation method comprises the following steps:
step A: respectively distilling herba Schizonepetae, radix Saposhnikoviae, Notopterygii rhizoma, radix Angelicae Pubescentis, radix Peucedani, rhizoma Ligustici Chuanxiong, and fructus Aurantii to obtain volatile oil, and respectively distilling the residue, rhizoma Ligustici Chuanxiong, and fructus Aurantii to obtain water solution;
and B: b, preparing the distilled water solution of the ligusticum wallichii and the fructus aurantii obtained in the step A into a 25% ethanol solution for later use;
and C: mixing Poria, the distilled rhizoma Ligustici Chuanxiong obtained in step A, and fructus Aurantii residue, percolating with the ethanol solution obtained in step B, and collecting percolate;
step D: decocting radix bupleuri, platycodon grandiflorum, liquorice, the distilled schizonepeta obtained in the step A, divaricate saposhnikovia root, notopterygium root, radix angelicae pubescentis and radix peucedani dregs with water twice, each time for 1.5 hours, combining decoctions obtained in the two times, filtering and concentrating into thick paste for later use;
step E: and D, mixing the percolate obtained in the step C and the thick paste obtained in the step D, standing, filtering, concentrating into clear paste, adding a proper amount of cane sugar, uniformly mixing, preparing into granules, drying, adding the volatile oil obtained in the step A, uniformly mixing, drying, crushing, sieving, adding 40-60 g of refined honey and a proper amount of water, pelleting, and drying to obtain the traditional Chinese medicine.
Second, pharmacodynamic test
In order to verify the efficacy of the traditional Chinese medicine composition in treating or improving the abdominal pain and the diarrhea, the inventor carries out related pharmacodynamic test research. It should be noted that the medicines selected in the pharmacodynamic tests below are the medicines obtained by the representative formula and the preparation method thereof; the inventor also conducts pharmacodynamic experiments on the medicines obtained by the other formulas and the preparation methods, and the experimental results show that the medicines obtained by the other formulas and the preparation methods have the same or similar effects, but the medicines are not exhaustive due to space limitations.
In addition, the following only takes part of animal models as examples to verify the efficacy of the present invention, the inventor also performs related pharmacodynamic experiments on abdominal pain and diarrhea caused by other reasons, and the experimental results show that the present invention has the same or similar effects, and the experiments are not exhaustive.
The inventor explains that the following experimental studies are carried out on the basis of the safety of the drug proved by acute toxicity tests and long-term toxicity tests, and the administration dose in the experimental studies is within a safe dose range.
First, the Chinese medicinal composition of the invention has the treatment effect on abdominal pain rats
1 Material
1.1 animals:
wistar rat, SPF grade, 180-220 g, laboratory animal license number: SYXK (lu) 20180008, provided by lumnan pharmaceutical group ltd, was acclimatized for one week prior to the experiment.
1.2 drugs, reagents
1.2.1 medicaments
Granules obtained in examples 1 and 2 of the present invention
Astragalus Jianzhong pills (Chinese medicine standard Z20025427)
1.2.3 dosage
Example 1 granules: 2.025g/kg (Low dose), 4.05g/kg (Medium dose), 8.1g/kg (high dose)
Example 2 granules: 4.05g/kg
Astragalus membranaceus Jianzhong pill: 1.62g/kg
2. Experimental methods
2.1 molding mode:
the molding process is divided into two major stages (both are free to drink water).
The first stage is that in the first 6 days, refined lard is fed for one day by 2mL/200g, and cabbage is fed for two days by l0g/200 g; swimming in 38 ℃ warm water every day until fatigue;
in the second stage, the water extract of the senna leaves is added for 7 to 21 days, and 2mL/200g of the water extract of the senna leaves is added every day.
The preparation method of the senna water extract comprises the following steps: soaking folium sennae in water for 30min, boiling for about 10min, filtering, and concentrating the filtrate to obtain 1:1 water extractive solution.
2.2 grouping and administration
60 successfully molded rats, a random model group, an astragalus mongholicus and Jianzhong pill group, three dose groups of example 1 (low, medium and high), and 10 rats in example 2 are selected. Another 10 rats were fed normally and were blank groups.
From experiment 22d, rats in each administration group were gavaged with the corresponding drug, and the blank group and the model group were gavaged with distilled water in equal amounts for 14 d.
3. Detecting the index
3.1 general case
In the experimental process, the appearance and activity conditions of rats, such as listlessness, crouching, bunching, slow reaction, withered and scattered fur, dirty anus, diet reduction, emaciation and the like, are observed. Before and after dosing, food intake and body weight changes were recorded.
3.2 visceral sensitivity assay
No water is forbidden 24h before detection. After ether anesthesia, a catheter lubricated with petroleum was inserted through the anus, with the balloon distal 1cm from the anus, and the catheter was fixed to the tail of the rat. After the rat revives, the rat is placed in a special plastic cage, and the rat can only move up and down but cannot move back and forth and turn around. After 30min acclimation period, changes in visceral sensitivity of rats were reflected by observation of abdominal wall withdrawal reflex (AWR) scores under colorectal distension stimulation under different pressure conditions (20mmHg, 30mmHg, 40 mmHg). Colorectal distension (CRD) stimulation each CRD pressure was 20s in duration and repeated 3 times, and the measured AWR scores were averaged over the last three times as the final abdominal wall withdrawal reflex (AWR) score at that distension pressure.
Grading standard: 0 point, the rat has no behavioral response to colorectal distension; 1 minute, the body is still when the colorectal is expanded, and the head movement is reduced or raised; 2 min, abdominal muscles contract when the colorectal is expanded, but the abdomen is not lifted off the table top; 3, abdominal muscle contracts and the abdomen is lifted off the table when the colorectal is expanded, and the patient is hoarsed; when the colon and rectum are expanded, the pelvis is lifted, and the body is arched.
3.3 measurement of the content of Substance P (SP), tumor necrosis factor alpha (TNF-alpha), neurotransmitter 5-hydroxytryptamine (5-HT) in blood
Collecting blood from rat vein, centrifuging, collecting blood plasma, and measuring contents of Substance P (SP) and neurotransmitter 5-hydroxytryptamine (5-HT) in blood plasma;
rats were bled intravenously, sera were separated and TNF- α levels in sera were determined.
3.4 statistical treatment
Statistical analysis is carried out on the obtained data by adopting SPSS22.0 software, and the data is measured
Figure BDA0002632554500000091
The results are shown in the following table, wherein the comparison among the groups is carried out by adopting one-factor analysis of variance, and the comparison between the two groups is carried out by adopting a T test mode. With P<A difference of 0.05 is statistically significant.
4. Results and conclusions
4.1 general case
Before the molding is started, the fur of each group of rats is white and glossy, and the mental state is good. After the model is built, rats show symptoms of listlessness, squinting, crouching, slow reaction, unstable walking, withered and lusterless fur, dirty anus, diet reduction, emaciation and the like
4.2 evaluation of visceral sensitivity
Compared with the blank group, the AWR score of the model group pups is obviously increased (p <0.01) under the stimulation of various CRD pressures (20mmHg, 30mmHg and 40 mmHg);
the AWR score was significantly reduced (p <0.05 or p <0.01) at CRD pressures of 20mmHg, 30mmHg and 40mmHg for each dosing group of rats compared to the model group.
Table 1 comparison of AWR scores at different expansion volumes for each group of rats (
Figure BDA0002632554500000101
n=10)
Figure BDA0002632554500000102
Note: in contrast to the blank group,P<0.05,#P<0.01;
in contrast to the model set,@P<0.05,*P<0.01;
compared with the radix astragali Jianzhong pill group,&P<0.05。
4.3 Effect on the levels of pain-causing Substances P (SP), tumor necrosis factor alpha (TNF-alpha), neurotransmitter 5-hydroxytryptamine (5-HT)
Compared with the blank group, the levels of SP, 5-HT and TNF-alpha in blood serum of the rats in the model group are obviously increased (P is less than 0.01); compared with the model group, the levels of SP, 5-HT and TNF-alpha in blood serum of rats in each administration group are reduced (p <0.05, p < 0.01).
TABLE 2 comparison of the SP, 5-HT in plasma and TNF-alpha content in serum of the various groups of rats: (
Figure BDA0002632554500000103
n=10)
Figure BDA0002632554500000104
Note: in contrast to the blank group,P<0.05,#P<0.01;
in contrast to the model set,@P<0.05,*P<0.01;
compared with the radix astragali Jianzhong pill group,&P<0.05。
secondly, the traditional Chinese medicine composition has the treatment effect on diarrhea rats
1 Material
1.1 animals:
wistar rat, SPF grade, 180-220 g, laboratory animal license number: SYXK (lu) 20180008, provided by lumnan pharmaceutical group ltd, was acclimatized for one week prior to the experiment.
1.2 drugs, reagents
1.2.1 medicaments
Granules obtained in examples 1 and 2 of the present invention
Shenling Baizhu Wan (Chinese medicine standard character Z37020850)
1.2.3 dosage
Example 1 granules: 2.025g/kg (Low dose), 4.05g/kg (Medium dose), 8.1g/kg (high dose)
Example 2 granules: 5.85g/kg
Ginseng, poria cocos and bighead atractylodes rhizome pills: 1.62g/kg
2. Experimental methods
2.1 molding mode:
cutting radix et rhizoma Rhei, adding appropriate amount of water, soaking in oven at 60-80 deg.C overnight, filtering, and concentrating the filtrate to obtain 2g/ml medicinal liquid. The rats are administrated with rhubarb liquid at a dose of 20ml/kg for intragastric administration 2 times a day, 1 time respectively in the morning and evening, and are molded for 10 days. Diarrhea in rats was observed and recorded.
2.2 grouping
60 rats successfully molded are randomly divided into a model group, a ginseng, poria and bighead atractylodes rhizome pill group, three dose groups of example 1 (high, medium and low), and 10 rats of example 2. Another 10 rats fed normally were selected as a blank group.
From day 11 onward, rats in each administration group were gavaged with the corresponding drug, and rats in the blank group and model group were gavaged with an equal amount of physiological saline for 7 days continuously.
3. Detecting the index
3.1 general State Observation in rats
The general state of the rats including hair gloss, mental state, food intake, activity, etc. was observed before administration in the morning and the body mass of the rats was recorded.
3.2 fecal Water content and diarrhea grade score
Collecting fresh feces of each rat before gavage administration in the morning on days 0, 7, 10 and 17 of the experiment, drying the fresh feces in an oven at 105 ℃ for 5 hours, measuring the moisture content of the feces, grading the feces form of each rat, and finally calculating the average value of all groups.
The degree of diarrhea in rats was scored on the following scale: 0 points indicate no diarrhea, normal stool, cylindrical; 1 point indicates diarrhea, thin, soft and tangible feces; 2 points indicate diarrhea, sticky feces, unformed feces and high water content; 3 points indicate diarrhea, liquid feces, unformed feces and watery feces.
Moisture content of feces (wet mass before drying-dry mass after drying)/wet mass before drying × 100%.
3.3 determination of Motilin (MTL), Gastrin (GAS), TNF-alpha, IL-10
After the last administration, the administration groups are fasted and not forbidden for 12 hours, blood is taken from abdominal aorta after anesthesia by 10% chloral hydrate, centrifugation is carried out, serum is taken, and the MTL and GAS levels and the contents of inflammatory factors TNF-alpha and IL-10 of each sample are measured by an ELISA method (the operation is carried out according to a kit method).
3.4 statistical treatment
Statistical analysis is carried out on the obtained data by adopting SPSS22.0 software, and the data is measured
Figure BDA0002632554500000121
The results of the two groups are shown in the specification, and the two groups are analyzed by a T test mode. With P<0.05 difference is statistically significant。
4. Results and conclusions
4.1 Effect on rat behavioral State and body Mass
After the model is made, the rats gradually suffer from the conditions of listlessness, trachoma and lassitude, anorexia, loose stool, dirty and lusterless hair color, fear of cold and preference for pricking, excrement stuck to the anus and the like along with the prolongation of the model making time, and the proctoptosis phenomenon of individual rats occurs; the rat body mass shows a descending trend, and compared with a blank group, the difference is significant (P is less than 0.01).
After the administration treatment, the fur of each administration group of rats is bright, active and active, the energy is vigorous, the forms of the food intake and the excrement are relatively normal, the body mass is obviously increased, and the difference is significant (P is less than 0.05 or P is less than 0.01) compared with that of a model group; compared with each administration group, the difference is not significant (P is more than 0.05).
TABLE 3 comparison of the results of the variation of body constitution of rats in each group: (
Figure BDA0002632554500000122
n=10,g)
Figure BDA0002632554500000123
Note: in contrast to the blank group,#P<0.01;
in contrast to the model set,@P<0.05,*P<0.01;
4.2 fecal Water content and diarrhea grade score
After the model is made, the moisture content of the rat feces is obviously increased, and compared with a blank group, the difference is significant (P is less than 0.01), and the rat feces are loose and not shaped, and the diarrhea score is obviously increased.
After the treatment, the moisture content of the feces of the rats in each administration group is obviously reduced, the diarrhea score is also obviously reduced, and the difference is significant compared with that in the model group (P is less than 0.01).
Table 4 comparison of stool water content results for various groups of rats (a)
Figure BDA0002632554500000131
n=10,%)
Figure BDA0002632554500000132
Note: in contrast to the blank group,#P<0.01;
in contrast to the model set,*P<0.01;
compared with the ginseng, tuckahoe and white atractylodes rhizome pill group,&P<0.05。
TABLE 5 comparison of diarrhea rating scores for rats in each group: (
Figure BDA0002632554500000133
n is 10 minutes)
Figure BDA0002632554500000134
Note: in contrast to the model set,*P<0.01;
compared with the ginseng, tuckahoe and white atractylodes rhizome pill group,&P<0.05,P<0.01。
4.3 Effect on Motilin (MTL), Gastrin (GAS)
Compared with the blank group, the motilin and the gastrin of the model group are obviously reduced, and the difference is significant (P is less than 0.01).
After the administration treatment, the motilin and the gastrin of rats in each administration group are obviously increased, and the difference has obvious difference compared with a model group (P <0.01)
TABLE 6 comparison of MTL and GAS content in rats of various groups: (
Figure BDA0002632554500000141
n=10)
Figure BDA0002632554500000142
Note: in contrast to the blank group,P<0.05,#P<0.01;
and model groupIn comparison, the method has the advantages that,*P<0.01;
compared with the ginseng, tuckahoe and white atractylodes rhizome pill group,&P<0.05。
4.4 Effect on inflammatory factors TNF-alpha, IL-10
Compared with the blank group, the TNF-alpha of the model group is obviously increased (P <0.01), and the inflammation is increased.
After the administration of the treatment, the TNF-alpha of rats in each administration group is reduced, and compared with a model group, the difference is significant (P is less than 0.01).
The anti-inflammatory factor IL-10 in the model group was significantly reduced (P <0.01) compared to the blank group.
After the administration treatment, the anti-inflammatory factor IL-10 of rats in each administration group is obviously increased (P is less than 0.05 or P is less than 0.01).
TABLE 7 comparison of stool water content results for various groups of rats: (
Figure BDA0002632554500000143
n=10)
Figure BDA0002632554500000144
Figure BDA0002632554500000151
Note: in contrast to the blank group,#P<0.01;
in contrast to the model set,@P<0.05,*P<0.01;
compared with the ginseng, tuckahoe and white atractylodes rhizome pill group,&P<0.05。

Claims (10)

1. a Chinese medicinal composition is prepared from Notopterygii rhizoma, radix Angelicae Pubescentis, Poria, radix Saposhnikoviae, herba Schizonepetae, rhizoma Ligustici Chuanxiong, radix Platycodi, bupleuri radix, radix Peucedani, fructus Aurantii, and Glycyrrhrizae radix, and can be used for treating and/or improving abdominal pain and diarrhea.
2. The use of claim 1, wherein the diarrhea comprises infectious diarrhea, non-infectious diarrhea.
3. The use according to claim 2, wherein the infectious diarrhea is diarrhea caused by infection with one or more of bacteria, viruses, fungi, and parasites.
4. The use of claim 2, wherein the non-infectious diarrhea is diarrhea caused by one or more of dietary factors, pharmaceutical factors, climatic factors, and disease factors.
5. The use of claim 4, wherein the disease agent includes, but is not limited to, gastric disease, intestinal disease, pancreatic disease, hepatobiliary disease.
6. The use of claim 1, wherein the abdominal pain is an abdominal pain caused by a disease of the digestive tract.
7. The use of any one of claims 1-6, wherein the traditional Chinese medicine composition is prepared from the following raw materials:
Figure FDA0002632554490000011
preferably, the traditional Chinese medicine composition is mainly prepared from the following raw materials:
Figure FDA0002632554490000012
further preferably, the traditional Chinese medicine composition is mainly prepared from the following raw materials:
Figure FDA0002632554490000013
8. a Chinese medicinal preparation, which is characterized by comprising the Chinese medicinal composition as claimed in any one of claims 1 to 4 and pharmaceutically acceptable auxiliary materials; preferably, the traditional Chinese medicine preparation is a clinically acceptable oral preparation; further preferably, the clinically acceptable oral preparation is one or more of pills, capsules, tablets, granules or liquid oral preparations; further preferably, the granules are Jingfang granules.
9. Use of the Jingfang granules of claim 8 in the manufacture of a medicament for treating and/or ameliorating abdominal pain, diarrhea.
10. A method for preparing the Chinese medicinal composition of any one of claims 1 to 7, wherein the method comprises the following steps:
step A: distilling herba Schizonepetae, radix Saposhnikoviae, Notopterygii rhizoma, radix Angelicae Pubescentis, radix Peucedani, rhizoma Ligustici Chuanxiong, and fructus Aurantii to obtain volatile oil, and collecting the residue, rhizoma Ligustici Chuanxiong, and fructus Aurantii water solution;
and B: b, preparing the distilled water solution of the ligusticum wallichii and the fructus aurantii obtained in the step A into a 10-40% ethanol solution for later use; and C: mixing Poria, the distilled rhizoma Ligustici Chuanxiong obtained in step A, and fructus Aurantii residue, percolating with the ethanol solution obtained in step B, and collecting percolate;
step D: decocting radix bupleuri, platycodon grandiflorum, liquorice, the distilled schizonepeta obtained in the step A, divaricate saposhnikovia root, notopterygium root, radix angelicae pubescentis and radix peucedani dregs in water, and concentrating the decoction for later use;
step E: and D, mixing the percolate obtained in the step C and the decoction obtained in the step D, concentrating, and adding the volatile oil obtained in the step A to obtain the composition.
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