CN113975288A - Application of α, β or γ cyclodextrin in the preparation of medicine for treating ulcerative colitis - Google Patents
Application of α, β or γ cyclodextrin in the preparation of medicine for treating ulcerative colitis Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
- A61K31/724—Cyclodextrins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
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- General Health & Medical Sciences (AREA)
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- Organic Chemistry (AREA)
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- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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Abstract
The invention discloses brand new application of alpha, beta and gamma cyclodextrins in treating ulcerative colitis, wherein the three cyclodextrins have obvious curative effects on the ulcerative colitis, can obviously inhibit DSS-induced colitis mouse weight reduction, obviously resist mouse colon tissue inflammatory cell infiltration and erosion, and obviously relieve mouse colon shortening, hematochezia and diarrhea.
Description
Technical Field
The invention relates to the field of medicaments, in particular to application of alpha, beta or gamma cyclodextrin in preparing a medicament for treating ulcerative colitis
Background
Cyclodextrin is a cyclic oligosaccharide containing at least 6D- (+) -glucopyranose units linked by alpha- (1,4) -glucosidic linkages, produced by enzymatic degradation of starch. The most common natural cyclodextrins are alpha-, beta-and gamma-cyclodextrins, which have different ring sizes and contain 6, 7 or 8 glucose units, respectively. Since the discovery of cyclodextrins since the end of the 19 th century, a number of related technical patents and scientific literature have accumulated. In the pharmaceutical field, cyclodextrin wraps drug molecules by virtue of a unique cavity structure to form an inclusion compound, can improve the bioavailability and solubility of the drug molecules, and is widely used as an excipient. In the food field, cyclodextrin is often used as a food additive to improve the mouthfeel of foods, and has high safety and low price. Alpha-cyclodextrin and beta-cyclodextrin are not digested in the gastrointestinal tract, but are fermented by the intestinal flora and support the growth and activity of probiotics such as bifidobacteria in the large intestine. Although gamma-cyclodextrin is partially digested in the upper digestive tract, it is not completely metabolized and the indigestible portion can also be fermented by the intestinal flora. In addition, the alpha-cyclodextrin, the beta-cyclodextrin and the gamma-cyclodextrin can be fermented and utilized by microorganisms in the intestinal tract to generate short-chain fatty acids (such as acetic acid, butyric acid and the like) which are beneficial to maintaining the barrier health of the intestinal tract.
Ulcerative Colitis (UC) is a common recurrent inflammatory disease of the intestinal tract, often accompanied by damage to the colonic mucosal barrier and hematochezia, often afflicting patients between 30 and 40 years of age, severely impairing their quality of life, increasing the risk of colorectal cancer. Recent epidemiological investigations have shown that the incidence and prevalence of ulcerative colitis is rapidly increasing worldwide, especially in europe and north america, followed by east asia. However, the exact cause of ulcerative colitis is currently unknown, and its explanation may be related to a complex immune inflammatory response between a dysfunction of the intestinal epithelial barrier and an imbalance of the gut's commensal flora. At present, the main medicines for treating ulcerative colitis, such as 5-aminosalicylic acid, corticosteroid, anti-TNF antibiotic and the like, can only relieve the symptoms of diseases and are accompanied by side effects and complications such as kidney diseases, psychological problems, vomit, anaphylactic reaction and the like. Therefore, there is an urgent need for a novel UC treatment or prevention drug with low toxicity and long-term use.
Disclosure of Invention
In view of the above, the present invention aims to overcome the disadvantages of the prior art and provide a medicament for treating ulcerative colitis with a significant effect.
In order to achieve the purpose, the invention adopts the following technical scheme:
the three cyclodextrins are all prepared into aqueous solution, and the dosage is 200mg/KG body weight.
As a further optimization of the scheme, the medicine adopts oral gavage.
Advantageous effects
The three cyclodextrins have obvious curative effects on ulcerative colitis, including the effects of obviously inhibiting the weight reduction of a DSS-induced colitis mouse, obviously resisting inflammatory cell infiltration and erosion of colon tissues of the mouse and obviously relieving the colon shortening, hematochezia and diarrhea of the mouse.
Drawings
FIG. 1 is a graph showing the effect of α, β and γ cyclodextrins of the present invention on disease activity index of ulcerative colitis Blab/c male mice, p <0.05, p <0.01, and p <0.001VS model group; # p <0.05, # # p <0.001VS normal group.
FIG. 2 is a graph showing the effect of α, β and γ cyclodextrins of the invention on body weight of male mice with ulcerative colitis Blab/c, the rate of decline being measured as p <0.05, VS model group compared to initial body weight; # p <0.05, # p <0.01VS normal group.
FIG. 3 is a graph showing the effect of α, β and γ cyclodextrins of the present invention on colon length of ulcerative colitis Blab/c male mice, particularly as a function of the colon length values,. p <0.05VS model group; # p <0.001VS Normal group.
FIG. 4 is a graph showing the effect of α, β and γ cyclodextrins of the present invention on the colon length of male mice with ulcerative colitis Blab/C, particularly colon section images of normal group (A), model group (B) and α, β and γ cyclodextrin 200mg/kg (C-E) treatment groups.
FIG. 5 is a graph showing the effect of α, β and γ cyclodextrins of the present invention on colon pathological changes of male mice with ulcerative colitis Blab/C, specifically, HE staining images of representative pathological tissue sections of normal group (A), model group (B) and α, β and γ cyclodextrins of 200mg/kg (C-E).
FIG. 6 is a graph showing the effect of α, β and γ cyclodextrins of the present invention on pathological changes in colon, specifically pathological scores of colon tissue damage, in ulcerative colitis Blab/c male mice, p <0.01VS model group; # p <0.01VS normal group.
Detailed Description
The technical solution in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and those who do not indicate specific conditions in the embodiments are performed according to conventional conditions or conditions suggested by manufacturers.
The alpha, beta and gamma cyclodextrins used in this example were purchased from Zhiyuan Biotech, Inc., Bingzhou, Shandong, and were dissolved in distilled water to prepare 20mg/ml, and the mice were gavaged at 200 mg/KG. The fecal occult blood detection kit is purchased from Nanjing Biotechnology Ltd, and DSS (Dextran Sodium Sulfate) is purchased from Nanjing gold Yibai Biotechnology Ltd.
The DSS-induced mouse colitis animal model is a classic acute ulcerative colitis molding method approved in the field of medicine, and is prepared into 2.5% aqueous solution. Reference documents:
Martina,and Anton Cerar.Dextran sodium sulphate colitis mouse model:traps and tricks.Journal of biomedicine&biotechnology vol.2012(2012):718617.
example 1 Effect of alpha, beta and gamma Cyclodextrins on disease Activity index in ulcerative colitis Blab/c Male mice
The tested drugs α, β and γ cyclodextrins were in three groups of 5 mice each. Each group of mice was gavaged with 200mg/kg of three aqueous solutions of cyclodextrin, while drinking 2.5% (w/v) DSS freely. 5 mice in the model group freely drunk 2.5% (w/v) DSS aqueous solution, mice in the normal group freely drunk clean distilled water, and both control groups were gavaged with an equal volume of physiological saline solution as a control. The experiment was performed for a total of 6 days, and at the end of day 7, the status of each group of mice was observed daily and body weight and fecal data were recorded.
The disease activity index includes the weight loss score, fecal trait score and fecal blood severity score of the mice, and the total score is the average of the three indices and is evaluated in the manner of table 1 below:
TABLE 1 disease Activity Scoring rules
The results are shown in figure 1, after DSS modeling, the mice have bloody stool and diarrhea, and the alpha, beta and gamma cyclodextrins of 200mg/kg can reduce the disease activity index of the mice, wherein the alpha and gamma cyclodextrins have better effect.
Example 2 Effect of alpha, beta and gamma Cyclodextrins on body weight in ulcerative colitis Blab/c Male mice
The test drug and mouse model were constructed in the same manner as in example 1. Body weight was 100% on day 0, on which basis body weight change was calculated in percent.
As shown in figure 2, after DSS modeling, the weight of the mice is continuously reduced, and 200mg/kg of alpha, beta and gamma cyclodextrin can relieve the reduction degree of the weight, wherein the effect of the gamma cyclodextrin is better.
Example 3 Effect of alpha, beta and gamma Cyclodextrins on Colon Length in ulcerative colitis Blab/c Male mice
The test drug and mouse model were constructed in the same manner as in example 1. Mice were sacrificed on day 7, the colons removed and length measured.
As shown in fig. 3-4, DSS modeling can therefore result in intestinal inflammation and bleeding, ultimately leading to a shortened colon length. 200mg/kg of alpha, beta and gamma cyclodextrin can obviously inhibit the shortening of colon, wherein the alpha and gamma cyclodextrin have better effect.
Example 4 Effect of alpha, beta and gamma Cyclodextrins on Colon pathological changes in ulcerative colitis Blab/c Male mice
The test drug and mouse model were constructed in the same manner as in example 1. On day 7, the mice were sacrificed, the colons were removed, 1cm long sections of intestine were cut from the end near the rectum and soaked in 4% paraformaldehyde, then paraffin-embedded, sectioned, HE-stained for changes in the intestinal wall structure and scored according to table 2, with the total histological score being the sum of the epithelial and infiltration scores. The scoring criteria are shown in table 2 below:
TABLE 2 Fine rules for intestinal histopathology scores
As shown in FIGS. 5-6, the DSS model resulted in inflammatory cell infiltration, crypt abscess formation, goblet cell loss, mucosal thickening, and abundant edema. Alpha, beta and gamma cyclodextrins at 200mg/kg all mitigated the above changes to varying degrees, with the effects of alpha and gamma cyclodextrins being more pronounced.
The above experimental results show that 200mg/kg of alpha, beta and gamma cyclodextrin can reduce the disease activity index of DSS-induced colitis in mice, reduce the degree of weight loss and colon shortening, with the alpha and gamma cyclodextrin being most effective.
It will be apparent to those skilled in the art from this disclosure that many changes and modifications can be made, or equivalents modified, in the embodiments of the invention without departing from the scope of the invention. Therefore, any simple modification, equivalent change and modification made to the above embodiments according to the technical essence of the present invention shall still fall within the protection scope of the technical solution of the present invention, unless the technical essence of the present invention departs from the content of the technical solution of the present invention.
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| CN202210185625.4A CN114404445B (en) | 2021-10-28 | 2022-02-28 | Application of cyclodextrin in preparation of medicine for treating ulcerative colitis |
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| AU2018342135A1 (en) * | 2017-08-28 | 2020-04-16 | Asdera Llc | Use of cyclodextrins in diseases and disorders involving phospholipid dysregulation |
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| CN113318241B (en) * | 2021-05-19 | 2022-09-20 | 浙江工业大学 | Magnolol disulfide bond cyclodextrin inclusion compound for ulcerative colitis and preparation method thereof |
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- 2021-10-28 CN CN202111262162.9A patent/CN113975288A/en active Pending
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114404445A (en) * | 2021-10-28 | 2022-04-29 | 中国药科大学 | Application of cyclodextrin in preparing medicine for treating ulcerative colitis |
| CN114404445B (en) * | 2021-10-28 | 2024-04-09 | 中国药科大学 | Application of cyclodextrin in preparation of medicine for treating ulcerative colitis |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114404445B (en) | 2024-04-09 |
| CN114404445A (en) | 2022-04-29 |
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Application publication date: 20220128 |