TWI688386B - Use of propanamide - Google Patents

Abstract

A use of propanamide in the manufacture of a medicine for improving activity of ATP synthesis is disclosed. Propanamide is administered to a subject in need thereof to improve activity of ATP synthesis, decreasing inflammation, reducing accumulation of visceral fat and lowering obesity-induced hyperglycemia.

Description

The use of acrylamide

The present invention relates to the use of acrylamide, in particular to the use of acrylamide for the preparation of drugs that enhance ATP synthesis activity.

Mitochondrion (mitochondrion) is an organelle that exists in eukaryotes. Its main function is to convert carbohydrates and fatty acids into adenosine triphosphate (ATP), which is the main energy in the cell. Source, when the activity of mitochondria is insufficient, it may cause diseases such as obesity, metabolic syndrome, insulin resistance, and even type 2 diabetes. In addition, the fat tissue of obese people secretes proinflammatory hormones, which can cause insulin resistance and increase blood sugar. Therefore, reducing the inflammatory response of obese people can also reduce insulin resistance and lower blood sugar, but there is no effective way to increase ATP synthesis activity and Anti-inflammatory drugs that reduce visceral fat and blood sugar, so there is still a need to provide the use of acrylamide to improve the aforementioned problems.

In order to solve the above problems, the object of the present invention is to provide a use of acrylamide, which is to apply acrylamide to the preparation of drugs that enhance the activity of ATP synthesis.

且係將丙醯胺投予一所需個體，以提升ATP合成的活性，進而降低發炎反應的發生、減少內臟脂肪的堆積及減低肥胖引起的高血糖現象；例如以每天每公斤體重投予11.56~15.38微克之劑量投予該所需個體，並於每餐飯後以經口服之方式投予該所需個體。如此藉由丙醯胺作為活性成分，藉由丙醯胺作為活性成分，可以有效提升ATP合成的活性，進而降低發炎反應的發生、減少內臟脂肪的堆積及減低肥胖引起的高血糖現象，為本發明之功效。 The use of acrylamide according to the present invention is to prepare a drug that enhances the activity of ATP synthesis. Acrylamide has the following chemical structural formula:

In addition, acrylamide is administered to a desired individual to increase the activity of ATP synthesis, thereby reducing the occurrence of inflammation, reducing the accumulation of visceral fat, and reducing the hyperglycemia caused by obesity; for example, 11.56 per kilogram of body weight per day A dose of ~15.38 micrograms is administered to the desired individual, and is administered to the desired individual orally after each meal. In this way, using acrylamide as the active ingredient and acrylamide as the active ingredient can effectively increase the activity of ATP synthesis, thereby reducing the occurrence of inflammation, reducing the accumulation of visceral fat and reducing the hyperglycemia caused by obesity. The effect of invention.

Figure 1: The chemical structural formula of acrylamide.

Figure 2: Test (A) ATP content in cells of each group.

Figure 3: Test (B) the concentration of tumor necrosis factor (TNF-α) secreted by the cells of each group into the culture medium; where * refers to P<0.05 compared to group B0; # Refers to P<0.05 compared with Group B1.

Figure 4: Test (C) The percentage of fat around the epididymis of mice in each group as a percentage of body weight; * means P<0.05 compared with group C0; # means compared with group C1 P<0.05.

Figure 5: Test (C) the blood glucose levels of mice in each group after fasting; where, * refers to the C0 Compared with the group, its P<0.05; # refers to the group C1, its P<0.05.

In order to make the above and other objects, features and advantages of the present invention more obvious and easy to understand, the following is a detailed description of preferred embodiments of the present invention, in conjunction with the attached drawings, as follows:

The “acrylamide” described in the present invention has the chemical structural formula shown in FIG. 1 and is often used as a chemical raw material to provide an amide group (-CONH ₂ ). Related medical reports.

The acrylamide system of the present invention can enhance the activity of ATP synthesis in cells, thereby reducing the occurrence of inflammation reaction of macrophages, reducing the accumulation of visceral fat and reducing the hyperglycemia caused by obesity, so it can be used to prepare the activity to enhance the activity of synthetic ATP The medicine, acrylamide and a pharmaceutically acceptable carrier or excipient are combined to form a pharmaceutical composition, and prepared into any convenient form, such as tablets, capsules, powders, granules or liquids, or Combine acrylamide with other foods or beverages and take it orally in an organism suitable for consumption.

In addition, the acrylamide of the present invention can be administered to a desired individual. For example, acrylamide can be administered to the desired individual at a dose of 15.8-21 mg per kg of body weight per day (for example, at each meal After a meal, it is administered orally to the desired individual), so that the acrylamide can exert its biological activity in the desired individual.

(A) Enhance the activity of ATP synthesis:

In order to confirm that the acrylamide of the present invention can indeed enhance the activity of ATP synthesis, the mouse macrophage cell line J774A.1 was tested, and the acrylamide at the concentration shown in Table 1 was added to each group of cells, and the Cells without acrylamide were taken as group A0. After 6 hours of culture, the ATP content in each group of cells was analyzed with an ATP luminometer, and the relative light unit (Relative light unit, RLU) as ATP content. The unit.

As shown in Figure 2, adding acrylamide to the cells can effectively increase the ATP content in the cells, showing that acrylamide has the ability to enhance the activity of ATP synthesis, and at a concentration below 4 μM, acrylamide enhances ATP synthesis The effect of the activity is positively correlated with its dose (dose-dependent response).

(B) Reduce the occurrence of inflammation:

Since enhancing the activity of ATP synthesis can change the activity of macrophages and inhibit the production of proinflammatory cytokine TNF-α, thereby reducing the occurrence of inflammatory reactions, as shown in Table 2, add acrylamide to each group of cells After 15 minutes, lipopolysaccharide (LPS) was used to induce inflammation in each group of cells. The cell culture supernatant of each group was collected and the content of TNF-α in each group was detected.

As shown in Figure 3, the addition of acrylamide to cells can not only effectively inhibit the production of the pro-inflammatory cytokine TNF-α induced by LPS (groups B3 and B5), but also between groups B0 and B2 or B4 Statistics found that acrylamide can also reduce the content of TNF-α, a proinflammatory cytokine not induced by LPS (groups B2 and B4), showing that acrylamide can indeed reduce the occurrence of inflammatory reactions.

(C) Reduce the accumulation of visceral fat and reduce the high blood sugar caused by obesity:

Generally speaking, cells will store excess energy in the form of fat, and mitochondria will lose 55% of the energy during ATP synthesis, so the increase in ATP synthesis activity can reduce the excess energy stored in the cell in the form of fat, and then To reduce the accumulation of visceral fat, as shown in Table 3, the mice in groups C1 and C2 were fed with high-fat feed for 17 weeks to induce obesity, and then the mice in group C1 continued to be fed on a high-fat diet for 2 weeks. The mice in group C2 were fed a high-fat diet containing 3 ppm acrylamide, while the mice in group C0 were fed a normal diet for 19 weeks. After 19 weeks, the mice in each group were sacrificed, and the fat content around the epididymis was analyzed to evaluate the effect of acrylamide on reducing the accumulation of visceral fat.

As shown in Figure 4, the fat content around the epididymis of group C1 mice fed a high-fat diet was significantly increased, while the fat content around the epididymis area of group C2 mice that ingested acrylamide was the same as feeding Group C0 mice on a normal diet showed similar results, showing that ingestion of acrylamide can effectively reduce the accumulation of visceral fat.

Before sacrificing the mice of each group, the mice of each group were fasted for 18 hours to measure their empty Abdominal blood glucose value, as shown in Figure 5, the fasting blood glucose value of the group C1 mice fed the high-fat diet was higher than that of the group C0 mice fed the normal diet, while the group C2 mice who also took acrylamide The fasting blood glucose value of rats has decreased significantly, showing that the intake of acrylamide can effectively reduce the high blood sugar caused by obesity.

In addition, according to the "Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers" guideline published by the US FDA, the metabolic coefficient of the mouse relative to the human body is 12.3, and it is based on the amount of feed and daily intake of the mice. For body weight, the recommended daily intake of a person converted to 60 kg is 694 to 923 micrograms (μg), and the converted dose is about 11.56 to 15.38 micrograms/kg.

In summary, by using acrylamide as the active ingredient, the activity of ATP synthesis can be effectively improved, and thus it can be applied to the preparation of drugs that enhance the activity of ATP synthesis, which is the effect of the present invention.

Furthermore, by enhancing the activity of ATP synthesis, the acrylamide of the present invention can not only reduce the occurrence of inflammatory reaction, but also reduce the accumulation of visceral fat and reduce the hyperglycemia caused by obesity, so it can be used in the preparation of anti-inflammatory Medicines, preparation of medicines for reducing visceral fat accumulation and preparation of medicines for reducing hyperglycemia caused by obesity are the effects of the present invention.

Although the present invention has been disclosed using the above-mentioned preferred embodiments, it is not intended to limit the present invention. Anyone who is familiar with this art without departing from the spirit and scope of the present invention still makes various changes and modifications to the above-mentioned embodiments. The technical scope of the invention is protected, so the scope of protection of the present invention shall be subject to the scope defined in the appended patent application.

Claims (4)

The use of acrylamide is to prepare a medicine for enhancing the activity of ATP synthesis. Among them, acrylamide has the following chemical structural formula:

In addition, acrylamide is administered to a desired individual to increase the activity of ATP synthesis, thereby reducing the occurrence of inflammation, reducing the accumulation of visceral fat, and reducing the hyperglycemia caused by obesity. The use of acrylamide as described in item 1 of the patent application scope, wherein acrylamide is administered to the desired individual by oral administration. The use of acrylamide as described in item 1 of the patent application scope, wherein acrylamide is administered to the desired individual at a dose of 11.56 to 15.38 micrograms per kilogram of body weight per day. The use of acrylamide as described in item 1 of the patent application scope, wherein acrylamide is administered to the desired individual after each meal.

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