CN114949131B

CN114949131B - Traditional Chinese medicine compound composition for treating Crohn's disease and preparation method thereof

Info

Publication number: CN114949131B
Application number: CN202210705158.3A
Authority: CN
Inventors: 沈洪; 朱磊; 刘亚军; 胡静怡
Original assignee: Jiangsu Provincial Hospital of Chinese Medicine
Current assignee: Jiangsu Provincial Hospital of Chinese Medicine
Priority date: 2022-06-21
Filing date: 2022-06-21
Publication date: 2023-03-28
Anticipated expiration: 2042-06-21
Also published as: CN114949131A

Abstract

The invention discloses a traditional Chinese medicine compound composition for treating Crohn's disease and a preparation method thereof, and the traditional Chinese medicine compound composition comprises 3-10 parts of scutellaria baicalensis, 5-12 parts of red peony roots, 3-10 parts of sophora flavescens, 3-10 parts of phellodendron barks, 10-20 parts of glabrous greenbrier rhizome, 3-10 parts of fried angelica, 3-10 parts of angelica dahurica, 3-10 parts of dried orange peels, 3-10 parts of fried bighead atractylodes rhizome, 3-10 parts of divaricate saposhnikovia roots, 3-10 parts of myrrh, 1-5 parts of nidus vespae, 5-12 parts of paniculate swallowwort roots, 7-15 parts of fried Chinese yams and 1-5 parts of raw liquorice. The traditional Chinese medicine compound composition for treating the Crohn's disease has the effects of clearing heat, promoting diuresis, removing blood stasis and dredging collaterals, provides an effective treatment medicine for clinically treating the intractable Crohn's disease, is economical and practical, has a wide clinical application prospect, and is simple, quick and efficient in preparation method, easy to operate, convenient to carry and convenient to take.

Description

Traditional Chinese medicine compound composition for treating Crohn's disease and preparation method thereof

Technical Field

The invention belongs to the field of traditional Chinese medicines, and relates to a traditional Chinese medicine compound composition for treating Crohn's disease and a preparation method thereof.

Background

Crohn's disease is a chronic, non-specific inflammatory disease of unknown cause, with a segmental or skip distribution, and involvement of the entire digestive tract, most commonly in the distal ileum and adjacent colon. Clinically, it is characterized by abdominal pain and diarrhea, and may be accompanied by bloody stool, fever, anemia, malnutrition, developmental disturbance, and other extra-intestinal manifestations such as pathological changes of joints, skin, eyes, oral mucosa and liver. As a chronic disabling disease, crohn's disease can present with fistulas, celiac abscesses, intestinal stenosis, intestinal obstruction, and perianal lesions, seriously affecting the quality of life of the patient. Wherein intestinal fibrosis seriously affects the quality of life of patients with crohn's disease.

Intestinal fibrosis is the most main reason of intestinal structural damage of Crohn's disease, is easy to cause obstruction and fistula formation, is also the most important factor influencing middle-term and long-term clinical outcomes, and no specific anti-fibrosis treatment means exists at present. In recent years, the application of biological agents brings about new eosin for treating the Crohn's disease, but a plurality of problems still need to be solved in clinic. In clinical practice, two biological agents with different inflammatory pathways are used in combination for treating the Crohn's disease which is not effective to multiple biological agents, but the risks of side effects, infection and the like, including the risk of tumors, can be increased when the biological agents are combined, and even if multiple biological agents are used for treating the Crohn's disease, only part of patients can realize long-term clinical relief, and the surgical resection risk is still high.

As the treatment characteristics of China, the traditional Chinese medicine treatment provides an optimizable treatment means for patients. According to the traditional Chinese medicine, the disease position of the Crohn's disease is in the stomach and intestine, is related to multiple internal organs such as spleen, liver, kidney, lung and the like, has the characteristics of wide disease position, deep disease, qi and blood synchronization and intestinal collateral damage, and belongs to the category of collateral diseases in the traditional Chinese medicine. The pathological nature is intermingled with deficiency and excess, and the intermingled deficiency and excess are usually cause and effect; the mixed cold and heat usually transform into each other; the same diseases of all zang organs, qi and blood deficiency, persistent and difficult to cure, and cluster of transformation syndrome.

Aiming at the traditional Chinese medicine pathogenesis of the Crohn's disease, namely damp-heat retention, qi and blood stasis stagnation and intestine collateral malnutrition, the treatment should clear heat and promote diuresis, remove blood stasis and dredge collaterals, eliminate the cause by eliminating the pathogenic factors of damp toxin, nourish blood, dissipate blood stasis and dredge collaterals to recover the original cause. At present, compound medicines with optimal medicine proportion are lacking clinically, and the compound medicines cannot be popularized and applied.

Disclosure of Invention

The invention aims to: the technical problem to be solved by the invention is to provide the traditional Chinese medicine compound composition for treating the Crohn's disease, which has the effects of clearing heat and promoting diuresis, and removing blood stasis and dredging collaterals, and can effectively treat the intractable disease of the Crohn's disease.

In order to solve the technical problems, the invention discloses a traditional Chinese medicine compound composition for treating Crohn's disease, which comprises the following components in parts by weight:

3 to 10 parts of scutellaria baicalensis, and the like,

5 to 12 portions of red paeony root,

3 to 10 parts of lightyellow sophora root,

3 to 10 parts of phellodendron bark,

10 to 20 portions of glabrous greenbrier rhizome,

3 to 10 parts of fried angelica sinensis,

3 to 10 parts of dahurian angelica root,

3 to 10 parts of dried orange peel,

3 to 10 parts of fried white atractylodes rhizome,

3 to 10 portions of divaricate saposhnikovia root,

3-10 parts of myrrh, namely, myrrh,

1 to 5 parts of nidus vespae,

5 to 12 portions of paniculate swallowwort root,

7 to 15 parts of fried Chinese yam,

1-5 parts of raw liquorice.

The dosage form of the traditional Chinese medicine compound composition is extractum, granules, tablets, capsules or liquid preparations.

The preparation method of the traditional Chinese medicine compound composition comprises the steps of adding water into the components according to the formula amount, decocting for 2 times, preferably, adding water for the first time, soaking, decocting for the first time, filtering, adding water for the second time, decocting for the second time, filtering, combining the two filtrates, and concentrating the filtrate under reduced pressure to obtain a concentrated solution.

Most preferably, the water is added for the first time, and the mass ratio of the water to the formula amount is 10:1; soaking for 1h; the first decoction lasts for 1h; and adding water for the second time, wherein the mass ratio of the water to the formula amount is 10:1; the second decoction lasts for 1 hour.

When the formulation is an extract, continuously concentrating the concentrated solution to obtain the extract;

or when the dosage form is granule, taking a proper amount of dextrin, placing in a fluidized bed, setting the air inlet temperature, feeding the concentrated solution, atomizing, finishing the spraying, drying, and preparing into granule;

or when the dosage form is tablet, concentrating the concentrated solution to obtain extract, mixing the extract with appropriate amount of dextrin, stirring, vacuum drying, pulverizing, sieving, adding ethanol, granulating, drying, grading, and making into tablet;

or when the dosage form is capsule, continuously concentrating the concentrated solution to obtain extract, mixing the extract with appropriate amount of dextrin, stirring, vacuum drying, pulverizing, sieving, adding ethanol, granulating, drying, grading, and making into capsule;

or when the dosage form is a liquid preparation, the concentrated solution is subjected to solid-liquid separation, the liquid part is taken, water is added, the mixture is stirred uniformly, packaged and sterilized, and the liquid preparation is prepared.

The vacuum concentration is carried out, the concentration vacuum degree is-0.08 to-0.04 MPa, the concentration temperature is 70 to 80 ℃, and the relative density of the obtained concentrated solution is 1.15 to 1.20 (60 ℃).

The dextrin serves as a binding agent in the preparation, and the dosage of the dextrin is adjusted according to the solid content and the finished product quantity of the finished product.

When the preparation form is extract, the relative density of the extract is 1.25 (60 ℃).

When the dosage form is granules, the air inlet temperature is 85-100 ℃; the liquid inlet speed of the concentrated solution is 80-150 r/min; the atomization is carried out under the conditions that the atomization pressure is 0.2MPa outside and the atomization pressure is 0.15MPa inside; and drying at 70 ℃ for 1h.

When the preparation is a tablet, the vacuum drying is carried out, the vacuum degree is-0.09 to-0.08 MPa, the drying temperature is 40 to 60 ℃, and the drying time is 24 hours; the sieve is an 80-mesh sieve; the purpose of adding the ethanol is to adjust the dryness and humidity of the traditional Chinese medicine particles, and the dosage of the ethanol is that the traditional Chinese medicine particles are held by hands to form a ball and are scattered by light pressure; and drying at 60 ℃ for 12h.

When the preparation is a capsule, the vacuum drying is carried out, the vacuum degree is-0.09 to-0.08 MPa, the drying temperature is 40 to 60 ℃, and the drying time is 24 hours; the sieve is an 80-mesh sieve; the purpose of adding the ethanol is to adjust the dryness and humidity of the traditional Chinese medicine particles, and the dosage of the ethanol is that the traditional Chinese medicine particles are held by hands to form a ball and are scattered by light pressure; and drying at 60 ℃ for 12h.

When the dosage form is a liquid preparation, the solid-liquid separation is centrifugation, and the rotating speed is 16000r/min; the volume ratio of water to filtrate is 20-40: 1; and (3) sterilizing at 100 ℃ for 30min.

The application of the traditional Chinese medicine compound composition in preparing the medicine for treating the Crohn disease is also within the protection scope of the invention.

The traditional Chinese medicine compatibility principle of the traditional Chinese medicine compound composition is as follows:

in the formula, the scutellaria is cold in nature and bitter in taste, and has the effects of clearing heat, drying dampness, purging fire and detoxifying; red peony root, radix Paeoniae Rubra is cool in nature and sour and bitter in taste, and has the effects of removing blood stasis, relieving pain, cooling blood and relieving swelling, and the two are used as monarch drugs together to clear away damp-heat and remove blood stasis. The lightyellow sophora root is cold in nature and bitter in taste, the golden cypress is cold in nature and bitter in taste, and the glabrous greenbrier rhizome is neutral in nature and sweet and light in taste, and the three medicines are used as ministerial medicines to assist the monarch medicines in clearing heat and removing dampness. The divaricate saposhnikovia root, the wasp nest, the paniculate swallowwort root and the cynanchum paniculatum are warm in nature and pungent in taste, and are used for removing dampness to relieve pain; the dried orange peel is warm in nature, pungent and bitter in flavor, the fried bighead atractylodes rhizome is warm in nature, bitter and sweet in flavor, and the fried Chinese yam is mild in nature, sweet and sweet in flavor, and the three are used together for regulating qi, tonifying spleen and removing dampness; stir-baked angelica is warm, sweet and pungent in nature, and can enrich blood and activate blood to relieve pain; radix Angelicae Dahuricae is warm in nature and pungent in flavor, myrrha is flat and bitter in flavor, the two are used together to relieve swelling and promote granulation to relieve pain, and the above nine ingredients are used as adjuvant drugs; the raw licorice root, radix Glycyrrhizae Praeparata, not only has the effects of invigorating the spleen and replenishing qi, clearing away heat and toxic material, and relieving spasm and pain, but also can harmonize the other drugs, and is used as a guiding drug.

Radix scutellariae

[ drug properties ]: bitter taste and cold nature, and they enter lung, gallbladder, spleen, large intestine and small intestine meridians.

[ efficacy ]: clear heat and dry dampness, purge fire and remove toxicity, cool blood and stop bleeding, remove heat and prevent abortion.

[ application ]: damp-warm fever, chest distress, damp-heat diarrhea, high fever, polydipsia and jaundice.

[ pharmacological ] of: has antiviral, antibacterial, antipyretic, hepatoprotective, gallbladder function promoting, spasmolytic, blood pressure promoting, diuretic, and tranquilizing effects.

Radix Paeoniae Rubra

[ drug properties ]: bitter in taste, slightly cold in nature, entering liver meridian.

[ efficacy ]: clear heat and cool blood, activate blood and dispel stasis.

[ application ]: heat entering nutrient-blood, macula due to warm toxicity, hematemesis and epistaxis, conjunctival congestion and swelling pain, liver depression and hypochondriac pain, amenorrhea and dysmenorrhea, addictions, abdominal pain, traumatic injury, carbuncle, swelling, sore and ulcer.

[ pharmacological ] of: has antithrombotic, hemostatic, antiaging, antibacterial, tranquilizing, heat clearing away, blood cooling, blood circulation promoting, blood stasis dispelling, and liver fire clearing away effects.

Sophora flavescens ait

[ drug properties ]: bitter taste and cold nature, entering heart, liver, stomach, large intestine and bladder meridians.

[ efficacy ]: clear heat and dry dampness, kill parasites and induce diuresis.

[ application ]: febrile dysentery, hematochezia, jaundice, scanty and brownish urine, leucorrhea with reddish discharge, swelling of the vulva, pruritus vulvae, eczema, skin pruritus, scabies, tinea, leprosy, trichomonas vaginitis.

[ pharmacological ] of: resisting pathogenic microorganism, relieving fever, resisting inflammation, resisting allergy, resisting tumor, and resisting arrhythmia.

Huang Bai

[ drug Property ]: bitter in taste and cold in nature, it enters kidney and bladder meridians.

[ efficacy ]: clear heat and dry dampness, purge fire and eliminate disease, remove toxicity and cure sore.

[ application ]: diarrhea due to damp-heat, jaundice, beriberi, night sweat, spermatorrhea, eczema.

[ pharmacological ] of: resisting pathogenic microorganism, resisting inflammation, lowering blood pressure, and resisting gout.

Rhizoma Smilacis Glabrae

[ drug properties ]: bland and sweet taste, warm in nature, entering stomach and liver meridians.

[ efficacy ]: detoxify, remove dampness, and smooth joints.

[ application ]: fire toxin furuncle, heat stranguria, scanty and brownish urine, astringing pain, contracture pain of tendons and bones.

[ pharmacological ] of: antibacterial and anticancer effects.

Parched radix Angelicae sinensis

[ drug properties ]: sweet and pungent in flavor, warm in nature, entering spleen, meridian and liver meridian.

[ efficacy ]: enrich the blood, remove blood stasis and relieve pain, maintain beauty and keep young.

[ application ]: blood deficiency, promoting blood circulation for removing blood stasis, warming and activating meridian, relieving pain and spasm, dysmenorrhea, asthenia cold type abdominal pain, traumatic injury, rheumatalgia, whitening and resolving macula.

[ pharmacological ] of: increasing coronary blood flow, resisting thrombi, enhancing immunity, resisting lipid peroxidation, resisting bacteria, resisting tumor, and resisting radiation.

Root of Dahurian Angelica

[ drug properties ]: pungent in flavor and warm in nature, it enters lung, stomach and large intestine meridians.

[ efficacy ]: relieving exterior syndrome, dispelling cold, dispelling pathogenic wind, relieving pain, dredging nasal orifice, eliminating dampness, stopping leukorrhagia, relieving swelling, and expelling pus.

[ application ]: wind-cold type common cold, headache, wind-damp arthralgia, nasal obstruction, nasal discharge and leukorrhagia.

[ pharmacological ] of: antipyretic, antiinflammatory, analgesic, spasmolytic, and anticancer effects.

Dried orange peel

[ drug properties ]: pungent and bitter in flavor, warm in nature, entering spleen and lung meridians.

[ efficacy ]: regulate qi, stimulate appetite, dry dampness, resolve phlegm, treat spleen and stomach diseases. Belongs to qi-regulating medicine.

[ application ]: it is indicated for fullness in chest and epigastrium, anorexia, vomiting, cough with profuse sputum.

[ pharmacological ] of: adjusting the digestive system; exciting the heart; has certain prevention effect on arteriosclerosis caused by high fat diet; relieving asthma and eliminating phlegm; the renal blood vessels are contracted, and the urine volume is reduced; enhancing immune function; anti-inflammatory; can promote secretion of digestive juice such as saliva and gastric juice, and eliminate intestinal gas accumulation.

Parched Atractylodis rhizoma

[ drug properties ]: bitter and sweet in taste, warm in nature and entering spleen and stomach meridians

[ efficacy ]: invigorate spleen, replenish qi, dry dampness, induce diuresis, strengthen superficies, check sweating and prevent abortion.

[ application ]: abdominal distension, diarrhea, edema, phlegm-fluid retention due to spleen deficiency and water-damp retention, spleen deficiency and qi weakness, and threatened abortion.

[ pharmacological ] of: regulating gastrointestinal function, enhancing cellular immunity, promoting urination, protecting liver, resisting tumor, promoting bile flow, lowering blood sugar, inhibiting bacteria, relieving cough, and tranquilizing mind.

Wind-proof

[ drug Property ]: pungent and sweet in flavor, slightly warm in nature, entering bladder, liver and spleen meridians.

[ efficacy ]: dispel wind and relieve exterior syndrome, subdue dampness and alleviate pain, stop spasm.

[ application ]: wind-cold, wind-heat, wind-damp arthralgia, rubella, pruritus and tetanus.

[ pharmacological ] of: antipyretic, analgesic, antibacterial, antishock, antiinflammatory, immunity enhancing, tranquilizing, anticonvulsive, gastric mucosa protecting, and spasmolytic effects.

Myrrha

[ drug Property ]: pungent and bitter with mild nature, entering heart, liver and spleen meridians.

[ efficacy ]: dispel stasis, relieve pain, resolve swelling and promote tissue regeneration.

[ application ]: chest stuffiness and pain, amenorrhea and dysmenorrhea, abdominal mass and pain, carbuncle, swelling, sore and ulcer, traumatic injury caused by blood stasis.

[ pharmacological ] of: reducing blood lipid, reducing hypercholesterolemia, preventing formation of atherosclerotic plaque, inhibiting bacteria, relieving inflammation, relieving pain, resisting tumor, protecting liver, and promoting enterokinesia.

Bee nest

[ drug properties ]: bitter in taste and neutral in nature, it enters liver, lung, stomach and kidney meridians.

[ efficacy ]: dispel wind and alleviate pain, relieve swelling with rose toxicity, kill parasites and relieve itching.

[ application ]: wind-warm arthralgia, wind-insect toothache, carbuncle, deep-rooted carbuncle, malignant boil, scrofula, swelling and pain of throat and tongue, anal fistula, rubella and pruritus, and intractable tinea.

[ pharmacological ]: antiinflammatory, heart contraction enhancing, temporary blood pressure lowering, and diuretic effects.

XU CHANGQING

[ drug Property ]: pungent in flavor and warm in nature, it enters liver and stomach meridians.

[ efficacy ]: promoting urination, tranquilizing, relieving pain, removing blood stasis, removing toxic substance, activating collaterals, promoting blood circulation, reducing blood lipid and lowering blood pressure.

[ application ]: can be used for treating various pain syndromes such as rheumatalgia, heart and chest pain, lumbago, toothache, traumatic injury, blood stasis and swelling pain, and dermatogic diseases such as eczema, rubella, skin pruritus, and intractable tinea.

[ pharmacological ] of: has analgesic, tranquilizing, coronary artery blood flow increasing, myocardial metabolism improving, myocardial ischemia relieving, and antibacterial effects.

Fried Chinese yam

[ drug properties ]: sweet in flavor, neutral in nature, entering lung, spleen and kidney meridians.

[ efficacy ]: to invigorate the spleen and nourish the lung, promote the production of body fluid and tonify the lung.

[ application ]: diarrhea due to spleen deficiency, chronic dysentery, cough due to asthenia, diabetes, frequent micturition, and anorexia due to spleen deficiency.

[ pharmacological ]: reducing blood sugar, regulating non-specific irritation reactivity, regulating immunity, and relieving diarrhea.

Radix Glycyrrhizae

[ drug properties ]: sweet in flavor, neutral in nature, entering heart, lung, spleen and stomach meridians.

[ efficacy ]: replenishing qi, strengthening the middle-jiao, expelling phlegm, arresting cough, relieving spasm and pain, harmonizing drug properties, clearing heat and removing toxicity.

[ application ]: heart-qi deficiency, spleen-qi deficiency, excessive phlegm, cough, spasm and pain of the abdomen, limbs, sores and ulcers due to heat-toxicity, and swelling and pain of the throat.

[ pharmacological ] of: has antiinflammatory, antiviral, liver protecting, toxic materials removing, immunity enhancing, blood lipid reducing, and atherosclerosis resisting effects.

Has the beneficial effects that:

the traditional Chinese medicine compound composition for treating the Crohn's disease has the effects of clearing heat, promoting diuresis, removing blood stasis and dredging collaterals, provides an effective treatment medicine for clinically treating the intractable Crohn's disease, is economical and practical, has a wide clinical application prospect, and is simple, quick and efficient in preparation process, easy to operate, convenient to carry and convenient to take.

Drawings

The foregoing and/or other advantages of the invention will become further apparent from the following detailed description of the invention when taken in conjunction with the accompanying drawings.

FIG. 1 is a graph of the effect of a combination on the body weight of mice in a Crohn's disease model;

FIG. 2 is a graph of the effect of the combination on colon length and colon weight in a Crohn's disease model mouse;

FIG. 3 is a graph of the effect of a combination composition on colon histopathology in a Crohn's disease model mouse;

FIG. 4 is a graph of the effect of the combination on colonic fibrosis in a Crohn's disease model mouse;

FIG. 5 is a graph of the effect of the combination on the expression of the fibrotic factor in mice model of Crohn's disease.

Detailed Description

The invention will be better understood from the following examples.

Example 1

A traditional Chinese medicine compound composition for treating Crohn's disease comprises the following components in parts by weight: 5 parts of scutellaria baicalensis, 6 parts of red peony root, 5 parts of sophora flavescens, 5 parts of phellodendron, 15 parts of glabrous greenbrier rhizome, 5 parts of fried angelica, 5 parts of angelica dahurica, 5 parts of dried orange peel, 5 parts of fried bighead atractylodes rhizome, 5 parts of divaricate saposhnikovia root, 5 parts of myrrh, 2 parts of nidus vespae, 8 parts of paniculate swallowwort root, 10 parts of fried Chinese yam and 2 parts of raw liquorice.

The preparation method comprises the following steps: decocting the 15 decoction pieces in water for 2 times, adding 10 times of water for the first time, soaking for 1 hour, decocting for 1 hour for the first time, filtering, adding 10 times of water for the second time, decocting for 1 hour for the second time, filtering, combining the two filtrates, and concentrating the filtrate under reduced pressure (the concentration vacuum degree is-0.08 to-0.04 MPa, and the concentration temperature is 70 to 80 ℃) to the relative density of about 1.20 (60 ℃). Taking 31.68 parts of dextrin, placing the dextrin in a fluidized bed, setting the air inlet temperature to be 85-100 ℃, starting to feed liquid when the material temperature is raised to 70 ℃, controlling the liquid feeding speed to be 80-150 r/min, controlling the atomization pressure to be 0.2MPa outside and 0.15MPa inside, finishing spraying, continuously drying for 1h at 70 ℃, and preparing 1000g of the dextrin to obtain granules.

Example 2

A traditional Chinese medicine compound composition for treating Crohn's disease comprises the following components in parts by weight: 8 parts of scutellaria baicalensis, 8 parts of red peony root, 6 parts of sophora flavescens, 6 parts of golden cypress, 15 parts of glabrous greenbrier rhizome, 8 parts of fried angelica, 8 parts of angelica dahurica, 8 parts of dried orange peel, 6 parts of fried bighead atractylodes rhizome, 8 parts of divaricate saposhnikovia root, 8 parts of myrrh, 2 parts of nidus vespae, 6 parts of paniculate swallowwort root, 8 parts of fried Chinese yam and 2 parts of raw liquorice.

The preparation method comprises the following steps: decocting the 15 decoction pieces in water for 2 times, adding 10 times of water for the first time, soaking for 1 hour, decocting for 1 hour for the first time, filtering, adding 10 times of water for the second time, decocting for 1 hour for the second time, filtering, combining the two filtrates, and concentrating the filtrate under reduced pressure (the concentration vacuum degree is-0.08 to-0.04 MPa, and the concentration temperature is 70-80 ℃) to the relative density of about 1.25 (60 ℃) to obtain the extract. Mixing the extract with 38.52 parts of dextrin, stirring uniformly, vacuum drying in a vacuum drying oven (the vacuum degree is-0.09 MPa to-0.08 MPa, the temperature is 40 ℃ to 60 ℃) for 24 hours, crushing the dry extract, and sieving by a sieve of 80 meshes. And (3) taking the extract powder, adding a proper amount of ethanol for granulation, drying the wet granules in a hot air circulation oven (at 60 ℃) for 12 hours, and finishing the granules. And (3) taking the granules after finishing, adding a lubricant magnesium stearate if necessary, uniformly mixing, calculating the weight of the tablets, and pressing into 1000 tablets to obtain the tablets.

Example 3

A traditional Chinese medicine compound composition for treating Crohn's disease comprises the following components in parts by weight: 8 parts of scutellaria baicalensis, 10 parts of red paeony root, 10 parts of radix sophorae flavescentis, 8 parts of golden cypress, 16 parts of rhizoma smilacis glabrae, 8 parts of fried angelica sinensis, 8 parts of angelica dahurica, 8 parts of dried orange peel, 10 parts of fried bighead atractylodes rhizome, 8 parts of divaricate saposhnikovia root, 10 parts of myrrh, 4 parts of nidus vespae, 10 parts of paniculate swallowwort root, 12 parts of fried Chinese yam and 4 parts of raw liquorice.

The preparation method comprises the following steps: decocting the 15 decoction pieces in water for 2 times, adding 10 times of water for the first time, soaking for 1 hour, decocting for 1 hour for the first time, filtering, adding 10 times of water for the second time, decocting for 1 hour for the second time, filtering, combining the two filtrates, and concentrating the filtrate under reduced pressure (the concentration vacuum degree is-0.08 to-0.04 MPa, and the concentration temperature is 70-80 ℃) to the relative density of about 1.25 (60 ℃) to obtain the extract. Mixing the extract with 48.24 parts of dextrin, stirring uniformly, vacuum-drying in a vacuum drying oven (vacuum degree is-0.09 to-0.08 MPa, temperature is 40-60 ℃) for 24 hours, crushing the dry extract, and sieving by a 80-mesh sieve. Adding appropriate amount of ethanol into the extract powder, granulating, drying the wet granules in a hot air circulation oven (60 deg.C) for 12h, and grading. And (4) taking the granules after the whole granules are finished, and filling the granules into capsules to obtain the capsules.

Example 4

A traditional Chinese medicine compound composition for treating Crohn's disease comprises the following components in parts by weight: 8 parts of scutellaria baicalensis, 10 parts of red paeony root, 8 parts of radix sophorae flavescentis, 10 parts of golden cypress, 15 parts of rhizoma smilacis glabrae, 8 parts of fried angelica sinensis, 10 parts of angelica dahurica, 8 parts of dried orange peel, 10 parts of fried bighead atractylodes rhizome, 10 parts of divaricate saposhnikovia root, 8 parts of myrrh, 5 parts of nidus vespae, 10 parts of paniculate swallowwort root, 12 parts of fried Chinese yam and 5 parts of raw liquorice.

The preparation method comprises the following steps: decocting the 15 decoction pieces in water for 2 times, adding 10 times of water for the first time, soaking for 1h, decocting for 1h for the first time, filtering, adding 10 times of water for the second time, decocting for 1h for the second time, filtering, combining the two filtrates, concentrating the filtrate under reduced pressure (the vacuum degree is-0.08 to-0.04 MPa, the temperature is 70-80 ℃) to the relative density of about 1.20 (60 ℃), centrifuging at high speed (the rotating speed is 16000 r/min), adding water (the volume ratio of water to the filtrate is 20), stirring uniformly, subpackaging, and sterilizing at 100 ℃ for 30min to obtain a liquid preparation.

Example 5

The traditional Chinese medicine compound composition for treating the Crohn's disease has the following treatment effect on a mouse model with the Crohn's disease:

the research method comprises the following steps:

1. preparation of the model

Preparation of a mouse model for Crohn's Disease (CD): after 1 week of adaptive feeding of BALB/C mice, 1 morning of the back was clipped at 1.5cm by 1.5cm, coated with 1% of 2,4, 6-trinitrobenzenesulfonic acid (TNBS) pre-sensitization solution; on the 8 th morning, enema was started, fasting was performed for 12 hours, and after anesthesia (isoflurane inhalation), 0.1mL of a 40% absolute ethanol solution prepared from a mixture of TNBS and absolute ethanol was administered to the enema, which was inserted from the anus, generally into a place with a length of 4-6 cm, with the head facing downward, and inverted for 1min. The dose (0.75 mg, 1.5mg, 2.5 mg) was gradually increased 1 time per week for a total of 7 times. After the enema is finished, in order to prevent the enema solution from overflowing out of the anus immediately, the rat tail needs to be lifted in time, the anus is lifted for 3min, the liquid medicine uniformly reaches the whole colon, and the molding is finished. For mouse recovery, a heating lamp was placed 20cm from the cage to keep the animals warm until recovery was good.

2. Experimental groups and drug intervention

The mice were randomly divided into 4 groups, a normal group (Ctrl group) of 5 mice, a model group (TNBS), a combination low dose group (TNBS + L,1.34975 g/mL), and a combination high dose group (TNBS + H group, 2.6995 g/mL). Normal control group: feeding the chicken regularly, and freely drinking water to eat the chicken; model group: after the model is made, equal volume of normal saline is given every day for intragastric administration; the preparation method of the compound medicine is the same as that in example 4, the filtrates are combined and concentrated to the concentrations of the high-dose group and the low-dose group, and the stomach irrigation administration of each group is 1 time/day from the first enema molding. The administration by gavage of each group was continued for 49 days.

3. Specimen collection method

After 49 days of administration, the mice were sacrificed by cervical dislocation after anesthesia, all colon tissues were taken out and washed rapidly with PBS, then the proximal tissues of the colon from the anus were cut off about 1cm, fixed in 10% formalin, fixed at room temperature, embedded in conventional paraffin, sliced 4-5 mm thick, subjected to conventional hematoxylin-eosin staining method (HE staining) and Masson trichrome staining, and then pathologically histopathologically examined and immunohistochemically examined, the mouse colon was observed and fibrosis assessed under a microscope, and the remaining tissues were immediately put into a-80 ℃ refrigerator for detection of other factor indexes of the fibrotic tissues of the colon.

3. Observation items

(1) General conditions of the mice: mice were observed daily for stool character, hair color, activity, mental status, and weighed and recorded daily.

(2) Pathology H & E detection and Masson staining of mouse colon tissue: after the model-making administration, the mice were sacrificed on day 49, the colon tissues of the mice were left to be fixed in 10% formalin, embedded in paraffin by a conventional method, the section thickness was 4-5 mm, conventional HE staining and Masson trichrome staining were performed, and the colon of the mice was observed and fibrosis was evaluated under a microscope. Gross colon observation, weighing all colon, measuring length and performing gross colon scoring, and the specific scoring is shown in table 1 below.

TABLE 1 gross score criteria for fibrotic colon morphology in mice

TABLE 1

And (4) observing under a mirror: the fibrosis characteristics of histopathology under the specimen section are observed, the severity of the fibrosis is evaluated, and relevant indexes under the microscope are scored according to the scoring standards shown in the following table 2.

TABLE 2 mouse fibrosis colonoscopy scoring criteria

(3) Colon fibrosis factor expression: the expression of mRNA of the fibrosis factors Fibronetin, alpha-SMA, N-Cadherin, E-Cadherin, col1 and TIMP1 in colon tissues of each group of mice was detected by a reverse transcription quantitative PCR (qRT-PCR) method.

4. Statistical treatment

Data processing is carried out by adopting Graphpad 8.0.1 statistical software, and results are expressed as mean +/-standard deviation

Is expressed in the form of a one-way anova with p<A difference of 0.05 is statistically significant.

The research results are as follows:

1. the weight condition is as follows: the mice were induced to model intestinal fibrosis by rectal administration of TNBS 1 time per week in a volume of 0.1mL and weekly in concentrations of 0.75% (g/mL), 1.5% (g/mL), 2.5% (g/mL). The compound low-dose group and the compound high-dose group are respectively and simultaneously administered with compound medicines with different concentrations for intervention, and the normal group and the model group are administered with distilled water with the same volume. 4 th to 7 th cycles: the body weight of the model group is obviously reduced compared with that of the normal group, and the body weight of the compound group is recovered (figure 1).

2. Colon length and colon weight: after the experiment was completed, the mice were euthanized with carbon dioxide. The colon length and the colon weight of the mouse are measured and recorded, the colon weight and the colon length and the colon weight of the model group are obviously increased compared with the normal group, and the ratio of the colon weight and the colon length and the ratio of the colon weight and the mouse weight are obviously reduced compared with the model group after the compound drying prediction is given (figure 2).

3. Colon histopathology: pathological colon of each group of mice is observed by H & E staining, the colon tissue structure of normal mice is clear, and inflammatory cells are not infiltrated; the pathological score of the model group mice with damaged colon tissue structure, inflammatory cell infiltration and colonic edema is higher than that of the normal group, the colon epithelial cell of the compound drug intervention group is normal in shape, the inflammatory cell is slightly infiltrated, and the pathological score is reduced compared with that of the model group (figure 3)

4. Masson staining: the colon fibrosis degree of each group of mice is inspected through Masson staining, the colon tissue structure of a normal mouse is clear, and the fibrosis layer of a muscle layer is thinner; the colon tissue structure of the mouse in the model group is damaged, the fibrosis degree is heavier, the collagen fiber score of the mouse is higher than that of the normal group, after the compound drug is administered, the colon epithelial cell shape is normal, the fibrosis degree is reduced, the collagen fiber score is reduced compared with that of the model group, and the statistical difference exists (figure 4).

5. Fibrotic factor expression in colon tissue: the mRNA expression of the fibrosis factors Fibronetin, alpha-SMA, N-Cadherin, E-Cadherin, col1 and TIMP1 in colon tissues of each group of mice is detected by a qRT-PCR method, and the mRNA expression of the fibrosis factors Fibronetin, alpha-SMA, N-Cadherin, col1 and TIMP1 in the colon of the model group of mice is obviously higher than that of the Ctrl group; the mRNA expression of fibrosis factors, namely fibrionetin, alpha-SMA, N-Cadherin, col1 and TIMP1, in colon tissues of compound dry prognosis mice is obviously reduced, and statistical difference exists; compared with the normal group, the expression of Cadherin E-Cadherin mRNA in the colon of the mouse in the model group is obviously reduced; the expression of E-Cadherin in colon tissues of mice given the compound dry prognosis is obviously increased and has statistical difference (figure 5).

In conclusion, the invention provides the application of the combined medicament in preventing and treating the Crohn's disease, the combined medicament can increase the weight of a mouse, the ratio of the colon weight to the colon length, improve the pathological structure and the fibrosis score of the mouse, change the expression of fibrosis genes, can be used as a potential medicament for preventing and treating the Crohn's disease, and provides a new medicament selection for clinic.

The invention provides a traditional Chinese medicine compound composition for treating Crohn's disease and a preparation method thereof, and a plurality of methods and ways for realizing the technical scheme are provided. All the components not specified in the present embodiment can be realized by the prior art.

Claims

1. A traditional Chinese medicine compound composition for treating Crohn's disease is characterized in that the composition comprises the following raw material medicines in parts by weight:

3 to 10 portions of baical skullcap root,

5 to 12 portions of red paeony root,

3 to 10 parts of lightyellow sophora root,

3 to 10 parts of amur corktree bark,

10 to 20 portions of rhizoma smilacis glabrae,

3 to 10 portions of fried angelica sinensis,

3 to 10 portions of dahurian angelica root,

3 to 10 portions of dried orange peel,

3 to 10 parts of roasted rhizoma atractylodis macrocephalae,

3 to 10 portions of divaricate saposhnikovia root,

3 to 10 parts of myrrh, namely,

1 to 5 parts of nidus vespae,

5 to 12 portions of paniculate swallowwort root,

7 to 15 parts of fried Chinese yam,

1 to 5 portions of raw liquorice.

2. The compound traditional Chinese medicine composition for treating Crohn's disease according to claim 1, wherein the dosage form of the compound traditional Chinese medicine composition is extractum, granules, tablets, capsules or liquid preparations.

3. The preparation method of the compound traditional Chinese medicine composition as claimed in claim 2, characterized in that the raw materials with the weight portion are decocted for 2 times by adding water, filtered, and the filtrate is decompressed and concentrated to obtain a concentrated solution;

or when the dosage form is capsule, concentrating the concentrated solution to obtain extract, mixing the extract with appropriate amount of dextrin, stirring, vacuum drying, pulverizing, sieving, adding ethanol, granulating, drying, grading, and making into capsule;

or when the dosage form is liquid preparation, separating solid and liquid from the concentrated solution, adding water into the liquid part, stirring, packaging, sterilizing, and making into liquid preparation.

4. The preparation method according to claim 3, wherein the concentration under reduced pressure is carried out under a vacuum degree of-0.08 to-0.04 MPa and at a concentration temperature of 70 to 80 ℃, and the relative density of the obtained concentrated solution is 1.15 to 1.20 (60 ℃).

5. The process according to claim 3, wherein when the dosage form is an extract, the extract has a relative density of 1.25 (60 ℃).

6. The preparation method according to claim 3, wherein when the dosage form is granules, the inlet air temperature is 85 to 100 ℃; the liquid inlet speed of the concentrated solution is 80 to 150r/min; the atomization is carried out under the conditions that the atomization pressure is 0.2MPa outside and the atomization pressure is 0.15MPa inside; and drying at 70 ℃ for 1h.

7. The preparation method according to claim 3, wherein when the dosage form is a tablet, the vacuum drying is carried out under the vacuum degree of-0.09 to-0.08 MPa, the drying temperature is 40 to 60 ℃, and the drying time is 24 hours; the sieve is an 80-mesh sieve; and drying at 60 ℃ for 12h.

8. The preparation method according to claim 3, wherein when the dosage form is a capsule, the vacuum drying is carried out under a vacuum degree of-0.09 to-0.08 MPa, the drying temperature is 40 to 60 ℃, and the drying time is 24 hours; the sieve is an 80-mesh sieve; and drying at 60 ℃ for 12h.

9. The preparation method according to claim 3, wherein when the dosage form is a liquid preparation, the solid-liquid separation is centrifugation at 16000r/min; adding water, wherein the volume ratio of water to filtrate is 20 to 40:1.

10. the use of the compound Chinese medicinal composition of claim 1 in the preparation of a medicament for the treatment of crohn's disease.