Application of pomalidomide in preparation of medicine for treating acute pancreatitis

Abstract

The invention provides an application of pomalidomide in preparation of a medicine for treating acute pancreatitis, and experiments show that 1. Pomalidomide can reduce generation of TNF-alpha and reduce pancreatitis reaction; and the development and progress of inflammation-related diseases can be controlled. And 2, the Pomalidomide can influence immune cells and inhibit generation of TNF-alpha by monocytes and macrophages, so that the inflammatory state and immune response are regulated. 3, Pomalidomide can intervene in a TNF-alpha signal channel, inflammatory response and tissue damage caused by TNF-alpha are reduced, and symptoms and clinical manifestation of inflammatory diseases can be improved.

Description

Technical Field

[0001] The invention relates to the technical field of drug application, and in particular to application of pomalidomide in preparing a drug for treating acute pancreatitis. Background Art

[0002] Acute pancreatitis (AP) is a common and critical disease of the digestive system, characterized by autodigestion of pancreatic tissue caused by abnormal activation of pancreatic enzymes. Inflammation is the main symptom of AP and the culprit of systemic inflammatory response. Therefore, reducing or inhibiting inflammation in AP is the primary goal of treating AP and preventing and treating severe cases. TNF-α (tumor necrosis factor-α) is an important proinflammatory cytokine that plays a key role in the process of acute pancreatic inflammatory response. When the pancreas is damaged or infected, acinar cells release a large amount of TNF-α, causing vasodilation, increased vascular permeability, and promoting inflammatory response of leukocytes. However, excessive or sustained TNF-α release may lead to uncontrolled inflammatory response, causing tissue damage and even multiple organ dysfunction syndrome. Therefore, regulating TNF-α levels is crucial to controlling the inflammatory response of acute pancreatitis. Summary of the invention

[0003] Based on this, the object of the present invention is to provide a use of pomalidomide in the preparation of a medicament for treating acute pancreatitis, so as to at least solve the deficiencies in the above-mentioned technology.

[0004] The invention provides the use of pomalidomide in preparing a medicine for treating acute pancreatitis.

[0005] As in the above application, the treatment of acute pancreatitis includes one or more of reducing the production of tumor necrosis factor, inhibiting the production of tumor necrosis factor by monocytes and macrophages, and intervening in the tumor necrosis factor signaling pathway.

[0006] As in the above application, the dosage of pomalidomide is 0.5 mg / kg.

[0007] Experiments show that 1. Pomalidomide can reduce the production of TNF-α and reduce pancreatic inflammatory response. It helps to control the development and progression of inflammatory-related diseases. 2. Pomalidomide can affect immune cells, inhibit monocytes and macrophages from producing TNF-α, thereby regulating the inflammatory state and immune response. 3. Pomalidomide can interfere with the TNF-α signaling pathway, reduce the inflammatory response and tissue damage caused by TNF-α, and help improve the symptoms and clinical manifestations of inflammatory diseases. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] Figure 1 This is the H&E staining image of mouse pancreas in the first embodiment of the present invention; Figure 2 This is a graph showing the pathological score of the mouse pancreas in the first embodiment of the present invention; Figure 3 This is the immunohistochemical staining diagram of MPO and F4 / 80 in mice in the first embodiment of the present invention; Figure 4 This is a mouse immunohistochemical staining scoring diagram of MPO and F4 / 80 in the first embodiment of the present invention; Figure 5 This is a graph showing the results of mouse serum amylase and lipase detection in the first embodiment of the present invention.

[0009] The following specific implementation manner will further illustrate the present invention in conjunction with the above-mentioned drawings. DETAILED DESCRIPTION

[0010] In order to facilitate the understanding of the present invention, the present invention will be described more fully below with reference to the relevant drawings. Several embodiments of the present invention are given in the drawings. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the disclosure of the present invention more thorough and comprehensive.

[0011] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which the present invention belongs. The terms used herein in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The term "and / or" used herein includes any and all combinations of one or more of the related listed items.

[0012] Embodiment 1 The present invention provides the use of pomalidomide in the preparation of a medicament for treating acute pancreatitis. The specific test method is as follows: 1. Establishment of SAP model in mice: C57BL / 6 mice were intraperitoneally injected with 50 μg / kg of caerulein for 10 consecutive times, with an interval of 1 hour between each administration. The model was established after the last injection and the mice were killed 24 hours later.

[0013] 2. Pomalidomide administration: Pomalidomide was dissolved in DMSO and PEG300, and prepared into low dose (0.5 mg / kg) and high dose (2 mg / kg), respectively. It was intraperitoneally injected into mice three days before modeling and after the first injection of caerulein.

[0014] 3. H&E staining was used to detect mouse pathology, observe pancreatic inflammation, edema, and necrosis, and perform scoring.

[0015] 4. Amylase and lipase: Both were tested using the Nanjing Jiancheng Bioengineering Research Institute kit. (A054-2-1, C016-1-1) 5. Immunohistochemistry experiments were used to detect the expression of inflammatory markers MPO and F4 / 80 in the pancreas of mice.

[0016] Experimental results: Based on the above steps, many inhibitors were selected for TNF-α, among which Pomalidomide had the most significant effect, as follows: 1. Pre-treatment with low-dose (0.5mg / kg) and high-dose (2mg / kg) Pomalidomide inhibitors for 3 days, and one injection after the first injection on the day of caerulein AP model establishment, the mice were killed 24 hours later and pathological examination was performed. H&E staining results showed that inflammation in AP of mice treated with 0.5mg / kg Pomalidomide was significantly reduced and acinar cell necrosis was significantly reduced, while the severity of the high-dose group was reduced but not significantly. The pathological score was also statistically significant (see Figure 1 to Figure 2 ).

[0017] 2. Immunohistochemical detection of the expression of MPO and F4 / 80 in mice showed that the inflammation of mice in the group treated with 0.5 mg / kg Pomalidomide was significantly reduced, especially in the MPO index that indicates acute inflammation. However, the reduction effect of the high-dose group was not significant (see Figure 3 to Figure 4 ).

[0018] 3. Detect the serum amylase and lipase of mice to observe whether it has an inhibitory effect on the release of pancreatic digestive enzymes. The results showed that the serum amylase of mice in the group using 0.5mg / kg Pomalidomide had a significant downward trend, while the serum lipase of mice using 2mg / kg Pomalidomide had a downward trend (e.g. Figure 5 as shown).

[0019] In summary, Pomalidomide in this embodiment has an important immunomodulatory effect in interacting with TNF-α. 1. Experiments have shown that Pomalidomide can reduce the production of TNF-α and reduce inflammatory responses. This helps to control the development and progression of inflammatory-related diseases. 2. Pomalidomide can affect immune cells, such as inhibiting the production of TNF-α by monocytes and macrophages, thereby regulating the inflammatory state and immune response. 3. Pomalidomide can intervene in the TNF-α signaling pathway, reduce the inflammatory response and tissue damage caused by TNF-α, and help improve the symptoms and clinical manifestations of inflammatory diseases. Overall, Pomalidomide affects the level and function of TNF-α through multiple pathways, thereby playing an important role in regulating inflammation and treating inflammatory diseases, such as rheumatoid arthritis, Crohn's disease, and psoriasis.

[0020] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0021] The above-mentioned embodiments only express several implementation methods of the present application, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for a person of ordinary skill in the art, several variations and improvements can be made without departing from the concept of the present application, and these all belong to the protection scope of the present application. Therefore, the protection scope of the patent of the present application shall be subject to the attached claims.

Claims

1. Use of pomalidomide in the preparation of a medicament for treating acute pancreatitis.

2. The use as claimed in claim 1, wherein the treatment of acute pancreatitis comprises one or more of reducing the production of tumor necrosis factor, inhibiting the production of tumor necrosis factor by monocytes and macrophages, and intervening in the tumor necrosis factor signaling pathway.

3. The use according to claim 1, wherein the dosage of pomalidomide is 0.5 mg / kg.

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