CN117224554A - Application of Capelliposide A in preparation of medicines for treating ulcerative colitis - Google Patents
Application of Capelliposide A in preparation of medicines for treating ulcerative colitis Download PDFInfo
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- CN117224554A CN117224554A CN202311032336.1A CN202311032336A CN117224554A CN 117224554 A CN117224554 A CN 117224554A CN 202311032336 A CN202311032336 A CN 202311032336A CN 117224554 A CN117224554 A CN 117224554A
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- capelliposide
- ulcerative colitis
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- 206010009900 Colitis ulcerative Diseases 0.000 title claims abstract description 31
- 201000006704 Ulcerative Colitis Diseases 0.000 title claims abstract description 31
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- UDBADKBPGCLKSD-UHFFFAOYSA-N Capilliposide C Natural products CC1(C)C2CCC3(C)C4(C)CC(O)C5(C(O)O6)C(OC7C(C(O)C(O)C(CO)O7)O)CC(C)(C)CC5C46CCC3C2(C)CCC1OC(C(C1O)OC2C(C(O)C(O)C(CO)O2)O)OCC1OC1OC(CO)C(O)C(O)C1OC1OCC(O)C(O)C1O UDBADKBPGCLKSD-UHFFFAOYSA-N 0.000 claims description 7
- OQQABMONOLWXGW-UHFFFAOYSA-N anagalligenin A 3-O-{beta-D-xylopyranosyl-(1->2)-beta-D-glucopyranosyl-(1->4)-[beta-D-glucopyranosyl-(1->2)]-alpha-L-arabinopyranoside} Natural products CC1(C)C2CCC3(C)C4(C)CC(O)C5(C(O)O6)C(O)CC(C)(C)CC5C46CCC3C2(C)CCC1OC(C(C1O)OC2C(C(O)C(O)C(CO)O2)O)OCC1OC1OC(CO)C(O)C(O)C1OC1OCC(O)C(O)C1O OQQABMONOLWXGW-UHFFFAOYSA-N 0.000 claims description 7
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 6
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an application of Capelliposide A in preparing a medicament for treating ulcerative colitis. The Capelliposide A can protect intestinal mucosa, relieve diarrhea, hematochezia and other symptoms caused by ulcerative colitis, has small toxic and side effects and has good development prospect.
Description
Technical Field
The invention belongs to the field of biological medicine, and in particular relates to an application of Capelliposide A in preparing a medicine for treating ulcerative colitis.
Background
Ulcerative colitis (Ulcerative colitis, UC) is an inflammatory bowel disease, which is mainly inflammatory and ulcerative lesions of the mucous membrane and submucosa of the rectum, sigmoid colon, and is mainly manifested by recurrent intense abdominal pain, diarrhea, rectal bleeding and hematochezia, and in severe cases can invade the whole colon and terminal ileum, even with risk of canceration. The disease was originally found in developed western countries but in recent years its incidence and prevalence have been increasing year by year and biased towards younger age throughout the world. UC has become a global disease threatening the health of humans. Many researches consider that the onset of UC is mostly related to host susceptibility genes, individual immune dysfunction, impaired intestinal barrier, intestinal flora imbalance, unhealthy eating habits and the like, but the specific etiology is still unknown, and the characteristics of long course, easy recurrence and many complications are added, so far, no cure strategy exists, and the UC is already listed as a modern refractory disease by the world health organization. The most commonly used intervention drugs in clinic at present mainly comprise three of 5-aminosalicylic acid, steroid hormone and immunosuppressant. Although the short-term curative effect is better, the long-term curative effect is still poor, the recurrence rate after stopping the medicine is high, the adverse reaction is large, and the like. Therefore, searching for natural anti-colitis drugs and adjuvant therapies that are efficient, safe, and free of toxic and side effects has become an urgent task to be solved in modern medical treatment.
Capelliposide A is oleanane triterpenoid saponin with a 13, 28-epoxy structure, has a certain anticancer effect, and has no research on the effect of the oleanane triterpenoid saponin in ulcerative colitis.
Disclosure of Invention
The invention discloses an application of Capelliposide A in preparing a medicament for treating ulcerative colitis.
The invention is realized by adopting the following technical scheme:
in a first aspect, the invention provides an application of Capelliposide A in preparing a medicament for treating ulcerative colitis, wherein the Capelliposide A has a structural formula as follows:
in a second aspect, the invention provides a medicament for treating ulcerative colitis, which is an administration suspension obtained by dissolving Capelliposide A in a sodium carboxymethyl cellulose solution; the structural formula of the Capelliposide A is as follows:
compared with the prior art, the invention has the beneficial effects that:
the invention provides a natural medicine for treating ulcerative colitis, which can well protect intestinal mucosa, relieve diarrhea, hematochezia and other symptoms caused by ulcerative colitis, has small toxic and side effects and has good application prospect.
Drawings
FIG. 1 is a graph showing the effect of Capelliposide A on body weight of mice with DSS-induced ulcerative colitis;
FIG. 2 is a graph showing the effect of Capelliposide A on DSS-induced ulcerative colitis mouse DAI;
FIG. 3 is a graph showing the effect of Capelliposide A on the colon length of DSS-induced ulcerative colitis mice;
FIG. 4 is a graph showing the effect of Capelliposide A on organ index in mice with DSS-induced ulcerative colitis;
FIG. 5 is a graph showing the effect of Capelliposide A on DSS-induced ulcerative colitis in mice colon tissue injury and inflammatory cell infiltration;
FIG. 6 is a graph showing the effect of Capelliposide A on expression of a barrier protein in colon tissue of a DSS-induced ulcerative colitis mouse.
In the figure: control is a normal Control; model was DSS Model group and treatent was Capilliposide a Treatment group.
In the figure: * Indicating significant inter-group variation (P < 0.05), indicating significant inter-group variation compared to significant P <0.01, indicating significant inter-group variation (P < 0.001), and indicating significant inter-group variation (P < 0.0001).
Detailed Description
The invention is further illustrated in the following, in conjunction with the accompanying drawings and specific embodiments.
The invention provides an application of Capelliposide A in preparing a medicament for treating ulcerative colitis, wherein the Capelliposide A has a structural formula as follows:
in the application, the Capelliposide A is taken as an active ingredient, and a corresponding pharmaceutical preparation can be prepared by adopting a pharmaceutically acceptable process and auxiliary materials and then is administrated. The effective dosage of Capilliposide A is 0.1 mg/kg body weight to 200 mg/kg body weight, and more preferably, the effective dosage of Capilliposide A is 1 mg/kg body weight to 100 mg/kg body weight.
In a subsequent embodiment of the invention, the drug for treating ulcerative colitis is an administration suspension obtained by dissolving Capelliposide A in a sodium carboxymethyl cellulose solution. Among them, the concentration of the sodium carboxymethyl cellulose solution is preferably 0.5%, and the concentration of Capelliposide A in the administration suspension is preferably 45mg/kg. This is but one pharmaceutical form and is not the only limitation of the present invention.
In theory, the above drugs may be oral preparations or external preparations. Wherein, if the medicine is an oral preparation, the medicine can be in the forms of capsules, granules, tablets, pills, powder and the like; if the medicament is in the form of external preparation, the medicament can be in the form of suppository, enema or gel, etc.
The symptoms corresponding to the medicament for treating the ulcerative colitis are ulcerative colitis, and particularly correspond to diarrhea, hematochezia symptoms and the like caused by the ulcerative colitis. Therefore, the medicine for treating ulcerative colitis can be used as a medicine for protecting intestinal mucosa and relieving diarrhea and hematochezia symptoms caused by ulcerative colitis.
In order to make the above objects, features and advantages of the present invention more comprehensible, the following embodiments accompanied with examples are further described. The invention is not limited to the embodiments listed but includes any other known modification within the scope of the claims that follow.
Example 1
The experiment in this example used SPF grade C57BL/6 mice (male, body weight 18-22 g), purchased from laboratory animal center in Zhejiang province.
Preparation of Capelliposide A administration suspension: weighing 5g of CMC-Na, preparing sodium carboxymethylcellulose (CMC-Na) solution with concentration of 0.5% by using 1000mL of deionized water, dissolving Capelliposide A to 45mg/kg by using the CMC-Na solution, and fully oscillating and uniformly mixing to obtain the Capelliposide A solution adopted in the subsequent administration. The Capelliposide A solution was stored in a refrigerator at 4℃and mixed well before each use.
Grouping, modeling and administration of animals: the experimental animals were selected from male C57BL/6 mice, and after the adaptive culture, the animals were randomly divided into a Control group, a Model group and a Treatent group, each group comprising 10 animals. The CMC-Na solution was administered to the Control group and the Model group for gavage 0.2 ml/day, the Treatment group was administered to the Capelliposide A solution prepared as described above 0.2 ml/day, and the gavage was continued until day 8, starting with the Model group and the Treatment group for increasing gavage 400mg/ml DSS solution 0.2 ml/day, the weights of the mice were weighed at the same time each day, the fecal status of the mice was observed, fecal occult blood (measured by benzidine method) conditions were evaluated, the severity of colitis was estimated, DAI scoring criteria was referenced to Murano et al and slightly modified (specifically as shown in Table 1), DAI= (weight fraction + fecal occult blood fraction)/3.
Table 1 scoring criteria table
Mice were sacrificed 5 days after continuous dosing, the whole colon (cecum distal to anus) was rounded, and length and weight were measured; each tissue was left, the weight of each set of organs was measured, and the organ index was calculated from the weight of the mice and the weight of the organs. The severity of intestinal lesions in mice was assessed by paraffin sections of the mice. The levels of coliform and Claudin (such as MUC-2, ZO-1, claudin-5 and Occludin) were determined by immunohistochemical methods.
The above experimental results of this embodiment are as follows:
1. general observations of mice:
the diet, drinking water, activity and defecation of the mice in the Control group are normal, and the hair is soft and bright and the mental state is good. The mice in the Model group have obvious weight reduction, reduced activity, reduced food intake, messy and matt hair, dry and rough hair, listlessness and hematochezia, loose stool and diarrhea, compared with the mice in the Treatment group which have obvious better hair color, spirit and movement conditions than those in the DSS Model group, the weight is obviously increased, and the better Treatment effect is shown, and the specific weight change is shown in figure 1.
Compared with the Control mice, the DAI score of the mice in the DSS Model group (Model group) starts to rise gradually with time, the disease condition of the colonitis is reflected to be aggravated gradually, and death condition occurs, and the DAI score of the mice in the Treatment group (Treatment group) has a descending trend, and the specific experimental result is shown in fig. 2.
The results of the colon length showed that the colon length of the mice of the Treatment group was significantly longer than that of the mice of the Model group, and the specific experimental results are shown in fig. 3.
The results of the organ indexes show that the organ indexes have no obvious change and small toxicity, and the specific experimental results are shown in figure 4.
2. Tissue injury scoring
H & E staining was used for pathology assessment. The Control group exhibited normal structural features with deep and long crypts, intact mucosa and abundant goblet cells. The Model group showed characteristics of colitis, damaged crypt, severe neutrophil infiltration, damaged mucosa, and goblet cell depletion. Compared with the Model group, the Treatment group has complete intestinal mucosa, the neutrophil infiltration degree is smaller, the damage degree of the crypt is lighter, and the result is shown in figure 5.
3. Intestinal barrier protein expression
Immunohistochemical methods were used to examine the expression of MUC-2, occludin, claudin-5 and ZO-1 in colon tissue. The significantly lower MUC-2, occludin, claudin-5 and ZO-1 expression in the Model group compared to the Control group indicated that the intestinal mucosa was damaged and the permeability was increased in the intestinal Model group, and the significantly higher MUC-2, occludin, claudin-5 and ZO-1 expression in the Treatment group compared to the Model group indicated that Capelliposide A promoted repair of the intestinal mucosa, maintained the integrity of the tight junctions, and reduced the permeability of the intestinal mucosa, as shown in FIG. 6.
It should be noted that the above embodiments are only for illustrating the technical solution of the present invention and not for limiting the same, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that the technical solution of the present invention may be modified or substituted without departing from the spirit and scope of the technical solution of the present invention, which is intended to be covered in the scope of the claims of the present invention.
Claims (10)
1. An application of Capelliposide A in preparing a medicament for treating ulcerative colitis, wherein the Capelliposide A has a structural formula as follows:
2. the use according to claim 1, wherein the effective dose of Capilliposide a is from 0.1 mg/kg body weight to 200 mg/kg body weight.
3. Use according to claim 1, wherein the effective dose of Capilliposide a is preferably 1 mg/kg body weight to 100 mg/kg body weight.
4. The use according to claim 1, wherein the medicament is prepared from Capilliposide a as an active ingredient by pharmaceutically acceptable auxiliary materials and processes.
5. The use according to claim 1, wherein the medicament is an oral formulation or an external dosage form.
6. The use according to claim 1, wherein the medicament is an oral formulation, in the form of a capsule, granule, tablet, pill or powder.
7. The use according to claim 1, wherein the medicament is in the form of a topical formulation, in the form of a suppository, enema or gel.
8. The use according to claim 1, wherein the medicament for treating ulcerative colitis is a medicament for protecting the intestinal mucosa and alleviating the symptoms of diarrhea and hematochezia caused by ulcerative colitis. .
9. A medicament for treating ulcerative colitis is characterized by being an administration suspension obtained by dissolving Capelliposide A in a sodium carboxymethylcellulose solution; the structural formula of the Capelliposide A is as follows:
10. a medicament for the treatment of ulcerative colitis according to claim 9, characterised in that the concentration of sodium carboxymethyl cellulose solution is 0.5% and the concentration of Capilliposide a in the administration suspension is 45mg/kg.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202311032336.1A CN117224554A (en) | 2023-08-16 | 2023-08-16 | Application of Capelliposide A in preparation of medicines for treating ulcerative colitis |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202311032336.1A CN117224554A (en) | 2023-08-16 | 2023-08-16 | Application of Capelliposide A in preparation of medicines for treating ulcerative colitis |
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- 2023-08-16 CN CN202311032336.1A patent/CN117224554A/en active Pending
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