Application of blood flow interruption in the preparation of medicine for treating ulcerative colitis

Abstract

The present invention relates to the field of medical technology, and specifically to an application of blood flow interruption in the preparation of a drug for treating ulcerative colitis. The present invention uses blood flow interruption to treat ulcerative colitis, which can effectively reduce the DAI score, inhibit the level of inflammatory factors in plasma, reduce the inflammatory response of colon mucosal tissue, play a protective role on the colon mucosa, and thus achieve its therapeutic effect, and has broad application prospects.

Description

Technical Field

[0001] The invention relates to the technical field of medicine, and in particular to an application of blood flow interruption in the preparation of medicines for treating ulcerative colitis. Background Art

[0002] Ulcerative colitis (UC) is a chronic nonspecific intestinal inflammatory disease, with lesions mainly in the rectum, colon mucosa and submucosa. Clinical manifestations include diarrhea, bloody stools with mucus and pus, and abdominal pain. It may also involve complications such as toxic megacolon, lower gastrointestinal bleeding, and intestinal perforation. Its pathogenesis is complex, and it is difficult to treat, recurrent, continuous, has a high recurrence rate, and is difficult to cure. In recent years, the prevalence of UC in my country has reached one in ten thousand, and there is a trend of increasing year by year.

[0003] In clinical practice, conventional treatment of UC relies on drugs such as aminosalicylic acid, corticosteroids, and immunomodulators. Long-term Western medicine treatment not only brings a huge economic burden to patients, but also causes recurrent attacks after treatment and is accompanied by serious side effects.

[0004] Duanxueliu, also known as mountain galangal, shade wind wheel, and hydrangea, is the dried aerial part of Clinopodium polycephalum (Vaniot) CYWu et Hsuan ex PSHsu or Clinopodium chinense (Benth.) O.Ktze. of the Labiatae family. It is included in the 2015 edition of the Chinese Pharmacopoeia. It tastes slightly bitter and astringent and is cool in nature. Duanxueliu has a long history of medicinal use in my country. It has the effects of cooling blood and stopping bleeding. It is mainly used to treat bleeding diseases such as metrorrhagia, hematuria, epistaxis, gum bleeding, traumatic bleeding, and uterine fibroid bleeding.

[0005] Previous related patents reported the role of total flavonoid extracts from Duanxueliu in the treatment and prevention of hemorrhagic diseases (Chinese patent: Total flavonoid extracts from Duanxueliu, preparation method and application, publication number: CN1891255A). This patent only studies the role of total flavonoid extracts from Duanxueliu in the treatment and prevention of hemorrhagic diseases. According to the ninth edition of "Internal Medicine" published by the People's Medical Publishing House: Hemorrhagic diseases are a group of diseases characterized by spontaneous or excessive bleeding after mild injury caused by defects or abnormalities in hemostatic mechanisms such as blood vessels, platelets, coagulation, anticoagulation and fibrinolysis due to congenital, hereditary and acquired factors. The pathogenesis of hemorrhagic diseases can be divided into abnormalities of vascular walls, abnormalities of platelets and abnormalities of the coagulation and fibrinolysis system. Bleeding caused by surgery, trauma or ulcers is not included.

[0006] The ulcerative colitis (UC) described in the present invention is a chronic nonspecific intestinal inflammatory disease, the main cause of which is the damage of the intestinal mucosal barrier, and does not belong to the category of hemorrhagic diseases. According to the ninth edition of "Internal Medicine" published by People's Medical Publishing House: The pathogenesis of UC is related to the abnormal intestinal immune imbalance caused by the interaction of multiple factors such as environment, genetics and intestinal microecology. Various factors cause the body's inflammatory pathway to activate, the secretion of inflammatory factors (such as IL-6, TNF-α, IL-4, etc.) increases, and the inflammatory factor / anti-inflammatory factor imbalance leads to persistent inflammation of the intestinal mucosa and damage to the barrier function.

[0007] Modern scientific research shows that Bronzed Blood Flow has anti-inflammatory, analgesic and antibacterial activities. There is no report on the use of Bronzed Blood Flow extract in the preparation of drugs for treating ulcerative colitis in the prior art. Summary of the invention

[0008] The present invention aims to provide an application of a cut-off blood flow extract in preparing a medicine for treating ulcerative colitis.

[0009] To achieve the above purpose, the present invention adopts the following technical solution:

[0010] A use of blood flow interruption in the preparation of medicine for treating ulcerative colitis.

[0011] The broken blood flow is the dried aerial part or dried whole grass of Clinopodium chinense or Clinopodium polycephalum of the Labiatae family.

[0012] The cut-off blood flow is a cut-off blood flow extract.

[0013] The blood-breaking extract is obtained by extracting the dried aerial parts or the dried whole grass of Pinus tabebuia and / or Perennial japonica through water or an organic solvent.

[0014] The blood flow extract comprises any one or more of the total extract, total flavonoids, total diterpenes and total triterpenes extracted from Pinus tabebuia and / or Perennial Herb.

[0015] The monomer compound Saturolide obtained by extraction from the cut-off blood flow is used in the preparation of medicine for treating ulcerative colitis.

[0016] The extraction method of the above-mentioned extract of the blood-breaking stream is as follows: take 50 kg of the dried whole grass of the blood-breaking stream, cut it into pieces, and immerse it in 10-15 times the amount of solvent for reflux extraction. Recover the solvent under reduced pressure to obtain an extract, extract it with petroleum ether, ethyl acetate and n-butanol, enrich the ethyl acetate layer extract on a polyamide column to obtain the total flavonoid extract of the blood-breaking stream. The n-butanol layer extract is chromatographed by D101 macroporous adsorption resin, and then eluted with 80% ethanol solution to obtain the total triterpenoid extract. The petroleum ether layer is concentrated to an extract, and chromatographed by AB8 macroporous adsorption resin to obtain the total diterpenoid extract. The monomer compound Saturolide is obtained by treating the ethyl acetate layer with an ODS column and HPLC.

[0017]

[0018] (3bR,5aR,7S,9aR,9bS)-5a-hydroxy-7,9b-dimethyl-7-vinyl-3b,4,5,5a,6,7,8,9

[0019] ,9a,9b,10,11-dodecahydrophenanthro[1,2-c]furan-1(3H)-one(Saturolide)

[0020] Furthermore, the extract, effective part and monomer of the blood flow interrupter are used as active ingredients and combined with pharmaceutically acceptable carriers, auxiliary materials or pharmaceutically acceptable excipients to form a pharmaceutical preparation.

[0021] The dosage form of the pharmaceutical preparation is liquid dosage form, solid dosage form, semi-solid dosage form, gas dosage form, and enema use, etc.

[0022] Among them, liquid dosage forms include mixtures, oral liquids, alcoholic preparations, tinctures, syrups, injections, etc.; solid dosage forms include powders, granules, tablets, capsules, pills, films, suppositories, and micropills; semisolid dosage forms include ointments, pastes, extracts, and licking preparations, etc.; gas dosage forms include aerosols, inhalants, etc.

[0023] The ulcerative colitis described in the present invention refers to a chronic nonspecific inflammatory bowel disease with mucus, pus and blood in the stool, abdominal pain and diarrhea as the main clinical manifestations. The pathological manifestations are large-area superficial ulcers in the rectum, colon mucosa and submucosa, and may also involve complications such as toxic megacolon, lower gastrointestinal bleeding, intestinal perforation, etc.

[0024] The cut-off blood flow extracts all have the effects of inhibiting weight loss and bloody stool in UC mice and reducing DAI scores.

[0025] Furthermore, the blood-broken extract has the effects of improving the inflammatory response caused by ulcerative colitis, improving tissue structure damage and protecting the colon mucosal barrier.

[0026] Furthermore, the blood-broken extract has the effect of increasing the content of colonic oxidative factor MDA in colon tissue and reducing the content of colonic oxidative factors SOD, GSH and inflammatory factor PGE2.

[0027] Furthermore, the blood flow extract has the effect of reducing the level of pro-inflammatory cytokines IL-6, TNF-α, and immunomodulatory factor INF-γ in plasma, and increasing the level of anti-inflammatory cytokine IL-4.

[0028] Furthermore, the cut-off blood flow extract can regulate and balance the body's immune system by adjusting the content of INF-γ and IL-4, thereby achieving the effect of alleviating inflammatory response.

[0029] Furthermore, the blood-broken extract can reduce the inflammatory response of colon mucosal tissue by inhibiting the level of NF-κB, thereby protecting the colon mucosa, and thus can be used in the preparation of drugs for treating ulcerative colitis.

[0030] Advantages of the present invention

[0031] The present invention firstly finds that when the broken blood flow extract is used to treat ulcerative colitis, it can effectively reduce the DAI score, increase the content of colonic oxidative factor MDA in colon tissue, reduce the content of colonic oxidative factors SOD, GSH and inflammatory factor PGE2, reduce the pro-inflammatory cytokines IL-6 and TNF-α in plasma, and increase the anti-inflammatory cytokine IL-4. It inhibits inflammatory factors in plasma, regulates autoimmunity, and thus improves the inflammatory response caused by ulcerative colitis, improves tissue structure damage and protects the colon mucosal barrier. At the same time, it reduces the inflammatory response of colon mucosal tissue by inhibiting NF-κB, exerts a protective effect on the colon mucosa, and thus achieves its therapeutic effect. The present invention has broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 is the hydrogen spectrum of the monomer compound Saturolide in Example 1 of the present invention;

[0033] Figure 2 is the carbon spectrum of the monomer compound Saturolide in Example 1 of the present invention;

[0034] Figure 3 This is a schematic diagram showing the effect of the cut-off blood flow extract obtained by extracting different raw materials in Example 3 of the present invention on the body weight of UC mice;

[0035] Figure 4This is a schematic diagram showing the effect of the blood flow extracts obtained by extracting different raw materials in Example 3 of the present invention on the DAI score of UC mice;

[0036] Figure 5 This is a schematic diagram showing the effect of the blood flow extracts obtained by extracting different raw materials in Example 3 of the present invention on the colon length of UC mice;

[0037] Figure 6 HE staining of colon of UC mice using the blood flow extracts obtained by extraction of different raw materials in Example 3 of the present invention;

[0038] Figure 7 This is a schematic diagram showing the effect of the blood flow extracts obtained by extracting different raw materials in Example 3 of the present invention on the contents of MDA and SOD in the colon tissue of UC mice;

[0039] Figure 8 This is a schematic diagram showing the effect of the cut-off blood flow extract obtained by extracting different raw materials in Example 3 of the present invention on the contents of IL-6, TNF-α, INF-γ and IL-4 in the plasma of UC mice; DETAILED DESCRIPTION

[0040] The application of Bronchodilator extract in treating ulcerative colitis is described in detail below through specific examples.

[0041] The extract of the Brocade Root of the present invention is extracted according to the Chinese herbal medicine extraction method recorded in "Technology of Extraction and Separation of Traditional Chinese Medicine"; for example, the raw material (Brocade Root) is extracted by water, alcohol and other solvents to obtain the extract material, and the obtained extract does not change its extraction components due to the different extraction solvents; further, the Brocade Root of the present invention can be obtained according to the following method: take the whole dry Brocade Root of the present invention (for example, Campanula or Lanterna), cut it into pieces, immerse it in a solvent (such as water, organic solvent, etc.) 10-15 times its mass, and reflux extract, that is, the Brocade Root of the present invention and the monomer compound Saturolide extracted from different raw materials are obtained, and set aside.

[0042] Example 1

[0043] The extraction method of the blood flow extract is as follows:

[0044] Take 50 kg of dried whole herb of Pinellia ternata, cut it into pieces, soak it in 750 L of 70% ethanol, heat it at 70°C and reflux it for extraction three times until the extract is relatively clear, which is considered to be complete extraction, that is, the blood flow extract;

[0045] The above-obtained extract is decompressed and the solvent is recovered to obtain an extract, which is then extracted with petroleum ether, ethyl acetate and n-butanol in sequence. The ethyl acetate layer extract is enriched on a polyamide column and eluted with 40%, 60% and 80% ethanol as eluents, respectively. 60% of the eluent is collected to obtain the total flavonoid extract of the cut-off blood flow.

[0046] The n-butanol layer extract was chromatographed with D101 macroporous adsorption resin, and then eluted with 40%, 60%, and 80% ethanol, and the 80% ethanol eluate was collected to obtain the total triterpenoid extract.

[0047] The petroleum ether layer is concentrated to an extract, and chromatographed on an AB8 macroporous adsorption resin, eluted with 70%, 80%, and 90% ethanol eluents, respectively, and 80% of the eluent is collected to obtain a total diterpenoid extract.

[0048] The monomer compound Saturolide was obtained by loading the total diterpene extract onto an ODS column and eluting with 40%, 60%, and 80% ethanol-water eluents. The 80% eluent was collected and then processed by HPLC using a methanol: water (80:100) system to obtain the monomer compound in about 27 minutes. (See Figure 1 and 2 )

[0049]

[0050] (3bR,5aR,7S,9aR,9bS)-5a-hydroxy-7,9b-dimethyl-7-vinyl-3b,4,5,5a,6,7,8,9,9a,9b,10,11-dodecahydrophenanthro[1,2-c]furan-1(3H)-one(Saturolide)

[0051] Meanwhile, the raw material was replaced with lantern grass and the above operation was followed to obtain the blood flow extract, which was further purified to obtain total flavonoids, total triterpenes extract and total diterpenes extract.

[0052] Example 2 Preparation

[0053] The extract, effective fraction and monomer of the blood flow interrupter of the present invention are active ingredients, and are combined with pharmaceutically acceptable carriers, auxiliary materials or pharmaceutically acceptable excipients to form a pharmaceutical preparation.

[0054] The dosage form of the pharmaceutical preparation is a liquid dosage form, a solid dosage form, etc.

[0055] Among them, liquid dosage forms include oral solution and injection; solid dosage forms include granules, tablets and capsules.

[0056] 2.1 Preparation of oral solution

[0057] Extracted from Pinus ternata:

[0058] Take 1 g of the fine powder of the cut-off blood flow extract, dissolve it in distilled water, adjust the pH value with a dilute sodium bicarbonate solution, add 0.05% potassium sorbate as a preservative, and then fill and sterilize.

[0059] Take 1 g of total flavonoid extract powder, dissolve it in distilled water, adjust the pH value with a dilute sodium bicarbonate solution, add 0.05% potassium sorbate as a preservative, and then fill and sterilize.

[0060] Take 1 g of total diterpenoid extract powder, dissolve it in distilled water, adjust the pH value with a dilute sodium bicarbonate solution, add 0.05% potassium sorbate as a preservative, and then fill and sterilize.

[0061] Take 1 g of total triterpenoid extract powder, dissolve it in distilled water, adjust the pH value with a dilute sodium bicarbonate solution, add 0.05% potassium sorbate as a preservative, and then fill and sterilize.

[0062] Take 1 g of the monomer compound Saturolide, dissolve it in distilled water, adjust the pH value with a dilute sodium bicarbonate solution, add 0.05% potassium sorbate as a preservative, and then fill and sterilize.

[0063] Extracted from Japanese lantern grass:

[0064] Take 1 g of the fine powder of the cut-off blood flow extract, dissolve it in distilled water, adjust the pH value with a dilute sodium bicarbonate solution, add 0.05% potassium sorbate as a preservative, and then fill and sterilize.

[0065] Take 1 g of total flavonoid extract powder, dissolve it in distilled water, adjust the pH value with a dilute sodium bicarbonate solution, add 0.05% potassium sorbate as a preservative, and then fill and sterilize.

[0066] Take 1 g of total diterpenoid extract powder, dissolve it in distilled water, adjust the pH value with a dilute sodium bicarbonate solution, add 0.05% potassium sorbate as a preservative, and then fill and sterilize.

[0067] Take 1 g of total triterpenoid extract powder, dissolve it in distilled water, adjust the pH value with a dilute sodium bicarbonate solution, add 0.05% potassium sorbate as a preservative, and then fill and sterilize.

[0068] 2.2 Preparation of tablets

[0069] Extracted from Pinus ternata:

[0070] Take 1 g of the severed blood flow extract, make it into fine powder, add appropriate amount of starch slurry as a binder and appropriate amount of starch as a diluent, and press it into tablets.

[0071] Take 1 g of total flavonoid extract, make it into fine powder, add appropriate amount of starch slurry as a binder and appropriate amount of starch as a diluent, and press it into tablets.

[0072] Take 1 g of total diterpenoid extract, make it into fine powder, add appropriate amount of starch slurry as a binder and appropriate amount of starch as a diluent, and press it into tablets.

[0073] Take 1 g of total triterpenoid extract, make it into fine powder, add appropriate amount of starch slurry as a binder and appropriate amount of starch as a diluent, and press it into tablets.

[0074] Take 1 g of the monomer compound Saturolide, make it into fine powder, add appropriate amount of starch slurry as a binder and appropriate amount of starch as a diluent, and press it into tablets.

[0075] Extracted from Japanese lantern grass:

[0076] Take 1 g of the severed blood flow extract, make it into fine powder, add appropriate amount of starch slurry as a binder and appropriate amount of starch as a diluent, and press it into tablets.

[0077] Take 1 g of total flavonoid extract, make it into fine powder, add appropriate amount of starch slurry as a binder and appropriate amount of starch as a diluent, and press it into tablets.

[0078] Take 1 g of total diterpenoid extract, make it into fine powder, add appropriate amount of starch slurry as a binder and appropriate amount of starch as a diluent, and press it into tablets.

[0079] Take 1 g of total triterpenoid extract, make it into fine powder, add appropriate amount of starch slurry as a binder and appropriate amount of starch as a diluent, and press it into tablets.

[0080] Example 3 Blood flow interruption efficacy verification experiment

[0081] 3.1 Experimental animals and materials

[0082] Experimental animals: 6-8 week old BALB / c mice.

[0083] Experimental materials: dextran sulfate sodium (DSS), mesalazine (5-ASA), the cut-off blood flow extract obtained in Example 1, various active fractions and monomers, paraformaldehyde, ethanol, hematoxylin and eosin staining kit, urine and fecal occult blood detection kit, enzyme-linked immunosorbent assay (ELISA) kit.

[0084] 3.2 Ulcerative colitis model and drug administration groups

[0085] After 1 week of adaptive feeding, 126 male BALB / c mice were randomly divided into 21 groups (n=6) using a random number table method: blank control group, model group, positive control (mesalazine) group and low- and high-dose groups of blood flow interruption drugs (high- and low-dose groups of C. chinense Extract (CE) (800 (CEH), 200 (CEL) mg / kg / d); high- and low-dose groups of C. chinense flavonoids (CF) (800 (CFH), 200 (CFL) mg / kg / d); high- and low-dose groups of C. chinense diterpenoids (CD) (800 (CDH), 200 (CDL) mg / kg / d); and high- and low-dose groups of C. chinense triterpenoids ( terpenoids, CT) high and low (800 (CTH), 200 (CTL) mg / kg / d) dose groups; monomer compound (Saturolide, SA) high and low (800 (SAH), 200 (SAL) mg / kg / d) dose groups. Lantern grass extract (C. polycephalum Extract, PE) high and low (800 (PEH), 200 (PEL) mg / kg / d) dose groups: Lantern grass total flavonoids (C. polycephalum flavonoids, PF) high and low (800 (PFH), 200 (PFL) mg / kg / d) dose groups; Lantern grass total diterpenoids (C. polycephalum diterpenoids, PD) high and low (800 (PDH), 200 (PDL) mg / kg / d) dose groups and Lantern grass total triterpenoids (C. polycephalum terpenoids, PT) high, low (800 (PTH), 200 (PTL) mg / kg / d) dose groups)

[0086] During the experiment, except for the blank control group mice given distilled water, the other groups drank 4% DSS aqueous solution freely for 7 consecutive days to induce UC mouse model, and the dosage was 5 ml / mouse / day. The drug was administered for 7 consecutive days, and the weight of mice in each group was weighed and marked before and after, and then each group was verified.

[0087] 3.3 Disease Activity Index (DAI) Assessment

[0088] During the experiment, the status of mice in each group was observed every day, and the mice were evaluated for DAI. The weight change, stool characteristics and fecal occult blood of each mouse were specifically recorded. The scoring criteria are as follows: percentage of weight loss (0, 0; 1%-5%, 1; 5%-10%, 2; 10%-20%, 3; >20%, 4); stool characteristics (normal, 0; soft stool, 1; mucous stool, 2; thin liquid stool, 3); fecal occult blood (negative, 0; light blue, 1; blue, 2; dark blue, 3; gross bloody stool, 4). The fecal occult blood test uses the urine and fecal occult blood test kit (benzidine method). The DAI score is the sum of the three indicators, see Figure 3 and Figure 4 .

[0089] In order to verify the therapeutic effect of the blood-cut extract on DSS-induced ulcerative colitis mice, the present invention conducted DAI evaluation on mice and investigated the weight, fecal characteristics, and occult blood of mice. Figure 3 and 4 It can be seen that compared with the control group, the weight of mice in the DSS modeling group was significantly reduced ( ### P<0.001, DAI score increased significantly ( ### P<0.001); Compared with the model group, the positive drug group and each dose group of UC mice showed significant inhibition of weight loss (***P<0.001) and inhibition of DAI score increase (***P<0.001). This shows that the broken blood flow extract has the function of improving DAI in ulcerative colitis mice, can effectively prevent and improve intestinal tissue pathological damage in ulcerative colitis mice, and has significant anti-ulcerative colitis activity.

[0090] 3.4 Colon length observation

[0091] At the end of the experiment, the mice were killed, and the spleens were dissected and collected for weight comparison. The entire colon was collected to observe the colorectal morphology and measure the colon length, see Figure 5 .

[0092] Depend on Figure 5 It can be seen that the epithelium in the colon tissue sections of the normal group mice was intact, and the crypt glands, matrix and submucosal structures were not damaged. The mucosal structure of the mice in the modeling group was significantly damaged, with a large area of ​​ulcers, thickening of the colon epithelium, edema of the submucosal layer, severe inflammatory cell infiltration, and severe damage to the colon tissue. Compared with the modeling group, the colon length of the UC mice in the drug-treated group was significantly prolonged and the ulcer area was reduced. The structural condition of the colon tissue was significantly improved. This shows that the blood flow cut extract has the function of improving inflammatory pathological damage to the intestinal tissue of mice, repairing ulcers, and improving the shortening of the colon length caused by ulcerative colitis.

[0093] 3.5 HE staining to observe colon tissue morphology

[0094] Preparation of mouse colon pathological tissue sections: The colon tissue of each group of mice at least 6 cm away from the anus was fixed with 10% paraformaldehyde, dehydrated with ethanol gradient, embedded in paraffin, and cut into thin slices with a thickness of 5 μm using a tissue slicer. The tissue morphology and severity of inflammation were observed under an optical microscope and scored using hematoxylin and eosin (HE) staining. The scoring criteria are as follows: 0, normal morphology, no inflammation; 1, mild inflammation, about 1 / 3 of the crypts were destroyed; 2, moderate inflammation, large-area goblet cell loss; 3, crypt loss, and extensive inflammatory infiltration of the muscularis mucosa; 4, crypt and epithelial cell loss, extensive inflammatory infiltration of the submucosal layer, see Figure 6 .

[0095] Depend on Figure 6 It can be seen that the epithelium in the colon tissue sections of the HE normal group mice was intact, and the crypt glands, matrix and submucosal structures were not damaged. The DSS model group showed severe inflammatory cell infiltration and severe damage to the colon tissue. Tissue damage and inflammatory cell infiltration in the drug-treated group mice were significantly improved. This shows that the dose groups of Duanxueliu extract improve colon tissue damage and reduce inflammatory reactions, which fully demonstrates the anti-inflammatory activity of Duanxueliu.

[0096] 3.6ELISA detection of inflammatory factor levels in plasma

[0097] ELISA method was used to detect the levels of IL-6, TNF-α, INF-γ and IL-4 in the plasma of each group of mice and the levels of MDA and SOD in the colon tissue homogenate according to the instructions of the kit.

[0098] IL-6 has strong pro-inflammatory activity and can induce a variety of pro-inflammatory mediators. TNF-α is a pleiotropic pro-inflammatory cytokine that is associated with the occurrence of a variety of diseases. In inflammatory diseases, immune cells usually preferentially activate CD4 + Helper T cells, namely Th cells; IFN-γ is the dominant cytokine of Th1 cells. Th1 cells mediate cell immunity. IFN-γ can promote T cells to polarize to Th1 and inhibit polarization to Th2. IL-4 is the dominant cytokine of Th2 cells. Th2 cells mainly mediate humoral immunity. IL-4 can promote T cells to polarize to Th2 and inhibit polarization to Th1.

[0099] Depend on Figure 7 and 8 It can be seen that ELISA test showed that compared with the control group, the levels of IL-6, TNF-α, and INF-γ in the plasma of the DSS modeling group were significantly increased ( ###P<0.001), compared with the model group, the content of pro-inflammatory cytokines in the positive drug group and each dose group of mice was significantly reduced (***P<0.001), and the content of anti-inflammatory cytokine IL-4 was significantly increased (***P<0.001). This shows that the broken blood flow extract can significantly reduce the levels of IL-6, TNF-α, and INF-γ in plasma, reduce the level of pro-inflammatory cytokines, and increase the level of anti-inflammatory cytokines. This fully demonstrates that the broken blood flow extract described in this application can achieve the effect of regulating the balance of Th1 and Th2 cell subsets by regulating the levels of different cytokines, thereby restoring the normal function and expression of the body's immune system.

[0100] ELISA was used to detect the contents of MDA and SOD in colon tissue homogenate. Compared with the control group, the MDA content in the DSS group mice was significantly reduced ( ### P<0.001, SOD content decreased significantly ( ### P<0.001). Compared with the model group, the MDA content in the colon tissue homogenate of the positive drug group and each dose group of mice increased significantly (***P<0.001), and the SOD content decreased significantly (***P<0.001). The results showed that the blood flow extract can significantly increase the MDA content in the colon tissue homogenate and reduce the SOD content, thereby achieving anti-inflammatory effects by regulating the level of anti-inflammatory factors in the body, alleviating ulcers and treating ulcerative colitis.

[0101] After verification of the above five embodiments, it can be concluded that the Broken Blood Flow extract has good anti-inflammatory activity, and can regulate and balance the normal function of the body's immune system by regulating the content of various inflammation-related cytokines such as TNF-α and IL-4 in the body, and promote autoimmunity, thereby achieving a therapeutic effect on ulcerative colitis. At the same time, the Broken Blood Flow extract can also reduce the inflammatory response and improve the inflammatory damage of the colon tissue structure by inhibiting the level of NF-κB. In addition, it can also regulate the level of anti-inflammatory factors such as SOD and MDA in the body, reduce the inflammatory response of the colon mucosal tissue, and play a protective role on the colon mucosa. Broken Blood Flow has a good application prospect for the treatment of ulcerative colitis.

Claims

1. Use of a broken blood flow extract in the preparation of a drug for treating ulcerative colitis, characterized in that: The blood-breaking flow is from the plant Pinellia oleracea of ​​the family Labiatae Clinopodium chinense or Pseudostellaria Clinopodium polycephalum The dried aerial parts or the dried whole grass; The blood-breaking extract is any one of the total extract, total flavonoids, total diterpenes and total triterpenes extracted from Pinellia ternata and / or Perennial Herb; The extraction method of the cut-off blood flow extract is: Take 50 kg of dried whole grass of Pinellia ternata, cut it into pieces, soak it in 750 L of 70% ethanol, heat it at 70 °C and reflux it for extraction three times until the extract becomes clear. This is considered to be the total extract of the blood-breaking flow. The above-obtained extract is decompressed to recover the solvent to obtain an extract, and then extracted with petroleum ether, ethyl acetate, and n-butanol in sequence, the ethyl acetate layer extract is enriched on a polyamide column, and eluted with 40%, 60%, and 80% ethanol as eluents, respectively, and 60% of the eluent is collected to obtain the total flavonoid extract of the cut-off blood flow; The n-butanol layer extract is chromatographed on a D101 macroporous adsorption resin, and then eluted with 40%, 60%, and 80% ethanol, and the 80% ethanol eluate is collected to obtain a total triterpenoid extract; The petroleum ether layer is concentrated to an extract, and chromatographed on an AB8 macroporous adsorption resin, eluted with 70%, 80%, and 90% ethanol eluents, respectively, and 80% of the eluent is collected to obtain a total diterpenoid extract.

2. Use of a monomer compound Saturolide extracted from cut-off blood flow in the preparation of a drug for treating ulcerative colitis, characterized in that: The monomer compound Saturolide is prepared by applying the total diterpenoid extract described in claim 1 to an ODS column, eluting with 40%, 60%, and 80% ethanol-water eluents, collecting 80% of the eluent, and then treating it with HPLC using a methanol:water ratio of 80:100 system to obtain a monomer compound at 27 minutes.

3. The use according to claim 1 or 2, characterized in that: The extract and monomer of the blood flow interrupter are used as active ingredients and are combined with pharmaceutically acceptable carriers to form a pharmaceutical preparation.

4. The use according to claim 3, characterized in that: The dosage form of the pharmaceutical preparation is liquid dosage form, solid dosage form, semisolid dosage form, and gas dosage form.

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