CN113712965B - Application of N, N, N ', N' -tetrayl (2-benzyl) -acetamide in preparation of medicine for treating UC - Google Patents
Application of N, N, N ', N' -tetrayl (2-benzyl) -acetamide in preparation of medicine for treating UC Download PDFInfo
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- CN113712965B CN113712965B CN202111110043.1A CN202111110043A CN113712965B CN 113712965 B CN113712965 B CN 113712965B CN 202111110043 A CN202111110043 A CN 202111110043A CN 113712965 B CN113712965 B CN 113712965B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
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- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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Abstract
The invention discloses an application of N, N, N ', N' -tetrayl (2-benzyl) -acetamide in preparing a medicament for treating Ulcerative Colitis (UC), wherein N, N, N ', N' -tetrayl (2-benzyl) -acetamide can relax a mesenteric arteriole, so that the functions of recovering mesenteric blood flow and maintaining intestinal mucosa barrier are achieved, a new thought is provided for the treatment of UC, and a new candidate medicament is provided for the treatment of UC.
Description
Technical Field
The invention relates to the field of biological medicine, in particular to application of N, N, N ', N' -tetrayl (2-benzyl) -acetamide in preparing a medicine for treating UC.
Background
Ulcerative Colitis (UC) is a global epidemic disease. In China, the number and incidence rate of UC patients are in a trend of rising year by year. UC obviously affects the health level of people in China, and serious complications caused by UC can threaten the life of patients. The existing medicines for treating UC are mainly divided into aminosalicylic acid medicines, glucocorticoid, biological preparations and the like. These therapeutic agents are often used to control disease symptoms, require long-term and even life-long administration, and have large drug side effects. The unclear pathogenesis of UC is a significant cause of the current lack of effective therapeutic drugs.
The current clinical drugs for treating UC mainly achieve limited efficacy of antisepsis and anti-inflammation by acting on microorganisms and inflammatory cells in the intestinal tract. There is an urgent need to find new drug targets from different fields of view to develop more effective therapeutic drugs. It is well known that intestinal submucosa microvasculature has an effective blood supply function, playing a key role in maintaining normal mucosal barrier function and histological structure; whereas in UC, the blood supply of the intestinal submucosal microvasculature is impaired. For example, the intestinal submucosal microvasculature of UC patients suffers from an impaired diastolic response to the vagal transmitter acetylcholine, resulting in reduced blood flow supply in the chronic inflammatory areas of the colon. Thus, on the one hand, it may lead to a decrease in the ability to clear inflammatory mediators, causing their localized accumulation, and on the other hand, to a decrease in the ability to repair after intestinal mucosal lesions in the chronic inflammatory area. Both will further exacerbate the damage of intestinal mucosal cells and the loss of mucosal barrier function, thereby promoting the occurrence and development of UC. Therefore, the dysfunction of the submucosal microvascular function of the intestine is probably an important basis for the refractory property of UC, and a new therapeutic means for clinically preventing and treating refractory UC by recovering the submucosal microvascular function is urgently needed.
Disclosure of Invention
In view of the above, it is an object of the present invention to provide an application of N, N, N ', N' -tetrayl (2-benzyl) -acetamide in preparing a medicament for treating ulcerative colitis.
In order to achieve the above purpose, the present invention provides the following technical solutions:
n, N, N ', N' -tetrayl (2-benzyl) -acetamide is used for preparing medicine for treating ulcerative colitis, and the structural formula of N, N ', N' -tetrayl (2-benzyl) -acetamide is shown in formula I.
Preferably, the concentration of N, N, N ', N' -tetrayl (2-benzyl) -acetamide is 5mg/mL.
Preferably, the N, N, N ', N' -tetrayl (2-benzyl) -acetamide is used for preparing medicine for dilating mesenteric arterioles.
Preferably, the use of said N, N, N ', N' -tetrayl (2-benzyl) -acetamide in the manufacture of a medicament for restoring weight or colorectal length in an ulcerative colitis animal.
The invention has the beneficial effects that: n, N, N ', N' -tetrayl (2-benzyl) -acetamide is used for treating UC, and the novel thought is provided for treating UC by dilating the mesenteric arterioles, so that the functions of recovering mesenteric blood flow and maintaining intestinal mucosa barrier are achieved.
Drawings
In order to make the objects, technical solutions and advantageous effects of the present invention more clear, the present invention provides the following drawings for description:
FIG. 1 is a graph of N, N, N ', N' -tetrayl (2-benzyl) -acetamide (TPEN) with the effect of dilating the mesenteric arterioles (A: N, N, N ', N' -tetrayl (2-benzyl) -acetamide (TPEN) is capable of dose-dependently dilating the mouse mesenteric arterioles pre-contracted with norepinephrine (NE; B: TPEN is capable of dose-dependently dilating the mouse mesenteric arterioles pre-contracted with NE instead of KCl);
FIG. 2 shows N, N, N ', N' -tetrayl (2-benzyl) -acetamide (TPEN) has the effect of alleviating UC in mice (A: weight measurement; B: colorectal length comparison; C: colorectal pathological section scoring comparison).
Detailed Description
The present invention will be further described with reference to the accompanying drawings and specific examples, which are not intended to limit the invention, so that those skilled in the art may better understand the invention and practice it.
N, N, N ', N' -tetra (2-benzyl) -acetamide in the present invention was purchased from MCE company (cat# HY-10448); DSS is purchased from mprio company in the united states; MPO detection kit was purchased from Abcam corporation (cat# ab 105136) of America.
Example 1
The method for dilating mouse mesenteric arterioles in vitro by using N, N, N ', N' -tetrayl (2-benzyl) -acetamide comprises the following specific steps:
A. after sacrifice of C57BL/6 mice by cervical dislocation, laparotomy was performed and mesenteries were excised and immediately immersed in ice-cold Krebs-Henseleit solution. The Krebs-Henseleit solution contains (mM): 118mM NaCl,4.7mM KCl,1.18 mM MgSO 4 、25mM NaHCO 3 、1.2mM KH 2 PO 4 、1.6mM CaCl 2 And 11.1mM D-glucose.
B. The mesenteric arterioles (second branch of superior mesenteric artery, length 2mm, straight) were obtained under microscopeDiameter of 100 to 150 μm). It was removed from the surrounding fat and connective tissue in Krebs-Henseleit solution and then mounted in a Mulvany wire electromyography (model 520A, DMT, denmark otti, denmark) for functional evaluation. The Powerlab analysis system (AD instruments Inc. of Colorado Springs, colorado) records changes in equiaxial tension. Two tungsten wires (40 μm in diameter each) were passed through the lumen of the microvasculature and secured to the jaws of the myoelectric recorder. Krebs-Henseleit solution (5 mL) was treated with 95% O at 37℃at room temperature 2 +5％CO 2 Continuously charging the gas mixture.
C. After arteriole installation, vessels were allowed to stabilize at zero tension for 20 minutes prior to normalization. After the equilibration period, the vessels were pre-contracted with 5. Mu.M Norepinephrine (NE), and after rinsing, different concentrations of N, N, N ', N' -tetrayl (2-benzyl) -acetamide were added for the experiment.
D. The detection results were statistically analyzed by Graphpad software (a in fig. 1). Statistics show that N, N, N ', N' -tetrayl (2-benzyl) -acetamide was able to dose-dependently relax the mesenteric arterioles of mice (B in fig. 1).
Example 2
A method for alleviating mouse UC using N, N, N ', N' -tetrayl (2-benzyl) -acetamide, comprising the steps of:
A. c57BL/6 mice at 6 weeks of age were randomly divided into control and experimental groups. Control mice received N, N, N ', N' -tetra (2-benzyl) -acetamide (10 mg/kg/day, intragastric), while experimental mice received either drinking water containing 2.5% DSS or a combination of 2.5% DSS plus N, N, N ', N' -tetra (2-benzyl) -acetamide (10 mg/kg/day, intragastric). All mice were treated for 7 days as experimental period and monitored daily throughout the experimental period by measuring body weight.
B. And carrying out statistics analysis on the detection result through Graphpad software. Statistics show that N, N, N ', N' -tetrayl (2-benzyl) -acetamide was able to restore body weight and colorectal length in DSS-colitis mice (fig. 2, a, b); at the same time, N, N, N ', N' -tetrayl (2-benzyl) -acetamide also was able to alleviate the extent of colorectal inflammation in DSS-colitis mice (fig. 2, c).
Thus, N, N, N ', N' -tetra (2-benzyl) -acetamide can be used to treat ulcerative colon.
The above-described embodiments are merely preferred embodiments for fully explaining the present invention, and the scope of the present invention is not limited thereto. Equivalent substitutions and modifications will occur to those skilled in the art based on the present invention, and are intended to be within the scope of the present invention. The protection scope of the invention is subject to the claims.
Claims (1)
- Use of N, N, N ', N' -tetrayl (2-benzyl) -acetamide in the preparation of a reagent for the in vitro diastole of mouse mesenteric arterioles in non-disease treatment.
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| CN202111110043.1A CN113712965B (en) | 2021-09-18 | 2021-09-18 | Application of N, N, N ', N' -tetrayl (2-benzyl) -acetamide in preparation of medicine for treating UC |
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