CN116808134A - Application of anti-aging tablet combined with metformin in preparation of medicine for preventing and/or treating type 2 diabetes - Google Patents
Application of anti-aging tablet combined with metformin in preparation of medicine for preventing and/or treating type 2 diabetes Download PDFInfo
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- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
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Abstract
The invention provides an application of anti-aging tablets combined with metformin in preparing a medicament for preventing and/or treating type 2 diabetes. In particular, the invention relates to an anti-aging tablet and the use thereof in combination with metformin for preparing a medicament for preventing and/or treating type 2 diabetes and/or energy metabolism disorder related thereto. The anti-aging tablet and the metformin can be used for synergistically regulating energy metabolism disorder caused by diabetes.
Description
Technical Field
The invention relates to the technical field of traditional Chinese medicines, in particular to an application of anti-aging tablets combined with metformin in preparing and/or treating type 2 diabetes medicines.
Background
Diabetes is a systemic metabolic disease characterized by hyperglycemia. With the rapid development of the socioeconomic level, the change of the population structure and the change of the life style of people, the incidence of diabetes is rising year by year. The global diabetes mellitus patients (20-79 years old) published by the international diabetes consortium in 2019 are about 4.63 million, and the number of global diabetes mellitus patients is expected to break through 7 million by 2045. Among them, type 2 diabetes is a major type of diabetes, accounting for about 90% of diabetes. The death and disability caused by diabetes have an increasing impact on the life span of human health and also severely threaten the quality of life of humans. Despite recent efforts to prevent and treat diabetes, the incidence of diabetes is still high. Therefore, new strategies and methods for controlling diabetes are still sought.
Type 2 diabetes is a metabolic disease characterized by chronic hyperglycemia, the basic pathology of which is absolute or relative deficiency of insulin secretion, and further causes metabolic abnormalities of energy and carbohydrates, fat, proteins, and the like. The release, transfer, storage and utilization of energy accompanying the metabolic process of a substance is called energy metabolism. The energy metabolism of type 2 diabetics is different from that of normal people to some extent, and the treatment of type 2 diabetes, whether it is dietary intervention, exercise or medicine, causes energy metabolism changes. Therefore, improving energy metabolism is of great importance for the prevention and treatment of type 2 diabetes.
Modern researches have shown that traditional Chinese medicine has a great advantage over western medicines in preventing and treating chronic diseases, metabolic syndrome, chronic complications and other diseases. The prescriptions and the Chinese patent medicines are taken as important components of the traditional Chinese medicine and are accepted by academia and patients for preventing and treating diseases of multiple organ systems. Type 2 diabetes is non-insulin dependent diabetes affected by multiple factors, is important in comprehensive prevention and treatment, and accords with the characteristic of treating diabetes by integrally regulating traditional Chinese medicine. Therefore, the traditional Chinese medicine is very helpful for preventing and treating diabetes mellitus, and western medicines are good at each. The anti-aging tablet is a Chinese patent medicine compound preparation developed on the basis of a palace secret prescription of Ming Yong le Tai Yi Su Miao Yi Yong Zhen Gao, and is prepared from six medicinal materials of radix rehmanniae, red ginseng, dwarf lilyturf tuber, radix asparagi, cortex lycii radicis and poria cocos. Wherein, the radix rehmanniae has the effects of clearing heat and cooling blood, the red ginseng has the effects of reinforcing primordial qi, the dwarf lilyturf tuber has the effects of nourishing yin and promoting the production of body fluid, the asparagus root has the effects of nourishing yin and moistening dryness, the cortex lycii radicis has the effects of clearing lung and reducing fire, and the poria cocos has the effect of strengthening spleen and calming heart. The composition has effects of invigorating qi, nourishing yin, replenishing blood, promoting salivation, tranquilizing mind, resisting aging, promoting health, and improving body function.
Disclosure of Invention
The technical purpose of the invention is to provide a new application of the anti-aging tablet in the treatment of type 2 diabetes and/or energy metabolism disorder related to the type 2 diabetes.
It is another technical object of the present invention to provide anti-aging tablets in combination with metformin having an effect of treating type 2 diabetes and/or energy metabolism disorders associated therewith.
In one aspect, the invention provides the use of an anti-aging tablet in the preparation of a medicament for preventing and/or treating type 2 diabetes mellitus and/or energy metabolism disorders associated therewith in a mammal, wherein the raw material medicament of the anti-aging tablet comprises radix rehmanniae, red ginseng, dwarf lilyturf tuber, asparagus root, cortex lycii radicis and poria cocos.
In a specific embodiment, the anti-aging tablet is produced by Zhengshengbao pharmaceutical company limited (national drug standard B20021021).
In particular embodiments, the anti-aging tablet can reduce blood glucose and glycosylated hemoglobin (HbA 1 c) levels in a mammal having type 2 diabetes.
In particular embodiments, the anti-aging tablet modulates an energy metabolism-related index in heart muscle and liver tissue of a mammal having type 2 diabetes, wherein the energy metabolism-related index in heart muscle comprises Adenosine Triphosphate (ATP), creatine Kinase (CK), lactate Dehydrogenase (LDH), and mitochondrial respiratory chain complexes i-iv (RCC i-iv); the index related to energy metabolism in liver tissue comprises adenylate activating protein kinase (AMPK), na + -K + ATPase and Glycogen (GP).
In another aspect, the invention provides the use of an anti-aging tablet in combination with metformin for the manufacture of a medicament for preventing and/or treating type 2 diabetes mellitus and/or energy metabolism disorders associated therewith in a mammal.
In particular embodiments, the anti-aging tablet in combination with metformin reduces blood glucose and HbA1c levels in mammals suffering from type 2 diabetes.
In particular embodiments, the anti-aging tablet in combination with metformin modulates an energy metabolism related index in heart muscle and liver tissue of a mammal suffering from type 2 diabetes, wherein the energy metabolism related index in heart muscle comprises ATP, CK, LDH and RCC i-iv; the related index of energy metabolism in liver tissue comprises AMPK and Na + -K + ATPase and GP.
In specific embodiments, the mammal includes a human, a rat, a mouse.
Compared with the prior art, the invention has the following positive and beneficial effects:
1. the invention provides an anti-aging tablet and application of the anti-aging tablet in reducing fasting blood glucose level of type 2 diabetes rats by combining with metformin, and provides assistance for prevention and treatment of type 2 diabetes and development and application of the anti-aging tablet.
2. The invention provides an anti-aging tablet and application of the anti-aging tablet in combination with metformin in regulating energy metabolism disturbance related to type 2 diabetes, and provides basis for development of drugs for treating the energy metabolism disturbance related to type 2 diabetes.
Detailed Description
The present invention will be described in further detail with reference to specific examples. However, the present invention is not limited to the following embodiments. The experimental methods in the following examples are all conventional methods unless otherwise specified; materials, reagents and the like used in the examples described below are commercially available from the public sources unless otherwise specified.
Terminology
In the present invention, the term "energy metabolism disorder associated with type 2 diabetes" means that in the pathological state of type 2 diabetes, the release, transfer, storage and utilization of energy accompanying the metabolism of substances in the body are hindered, thereby affecting the metabolism of the body.
Unless otherwise specified, 60 SPF-grade male SD rats (180-220 g) were used in the following examples, purchased from Kwansi laboratory animal Co., ltd. [ license number: SYXK 2017-0040, free diet, drinking water, temperature of 22-26 ℃, humidity of 50-55% and illumination period of 12h. The high-fat feed (batch number: DZ20200813, purchased from Jiangsu province collaborative medical bioengineering Co., ltd.) is prepared by adding 20.0% sucrose, 15% lard, 1.2% cholesterol, 0.2% sodium cholate, etc. into basic feed.
The medicine and the reagent used are as follows: anti-aging tablet (lot number: 1912807, zhengshenbao pharmaceutical Co., ltd.); metformin hydrochloride tablet (lot number 2020705, mitsui Shanghai Guibao pharmaceutical Co., ltd.); streptozotocin (STZ; lot number: 201831517, sigma); hbA1c (lot number: MM-21055R 1); AMPK (lot number: MM-61506R 1); na (Na) + -K + ATPase (lot number: MM-43903R 1); CK (lot number: MM-20460R 1); ATP (lot number: MM-46058R 1); RCC I (lot number: MM-70189R 1); RCCII (lot number: MM-70264R 1); RCCIII (lot number: MM-70191R 1) and RCC IV (lot number: MM-70266R 1) ELISA kits were purchased from enzyme-linked immunosorbent assay (Jiangsu, china). The GP (lot number: E-BC-K073-S) and LDH (lot number: E-EL-R0338 c) ELISA kits were purchased from Elabscience (Wuhan, china).
Example 1: anti-aging tablet and effect of combined use of metformin on blood sugar and glycosylated hemoglobin level of type 2 diabetic rats
Male SD rats weighing 180-220g were acclimatized for one week and then randomly divided into normal groups (n=10, given normal feed feeding) and model building groups (n=50, given high fat feed feeding). After 4 weeks, the model-making rats were injected with 55mg/kg of STZ intraperitoneally, and after 72 hours of STZ injection, the fasting blood glucose level of the rats was detected, and the blood glucose value was not less than 16.7mmol/L, which was considered as successful in the preparation of the diabetes model. Rats successfully molded were randomly divided into 5 groups of a model group, an anti-aging tablet low dose group (306 mg/kg), an anti-aging tablet high dose group (612 mg/kg), a metformin group (229.5 mg/kg) and an anti-aging tablet low dose+metformin group (306 mg/kg+229.5 mg/kg), each group being 10. The administration dosage is obtained according to the clinical dosage of the anti-aging tablet and the adult metformin and the equivalent dosage conversion coefficient of rats and human beings. Each administration group was treated with the corresponding drug, and the normal group and the model group were administered with an equal amount of physiological saline, followed by administration by gastric lavage for 8 weeks. While the animals except the blank group were continuously fed with the high-fat diet. Body weight was measured once a week, blood was collected after the end of the experiment, and serum hollow abdominal blood glucose (FBG) and glycosylated hemoglobin (HbA 1 c) levels were measured.
TABLE 1 Effect of anti-aging tablet and metformin in combination on FBG and HbA1c levels of type 2 diabetic rats
Comparison to the control group: △ P<0.05， △△ P<0.01; comparison to model set: * P<0.05， ** P<0.01; compared with the low dose group of anti-aging tablets: ▲ P<0.05， ▲▲ P<0.01; in comparison with the group of metformin, ※ P<0.05， ※※ P<0.01。
experimental results: the results of the effects on FBG and HbA1c are shown in the table 1, and the experimental results show that the FBG and HbA1c levels of the rats in the model group are obviously increased (P < 0.01), the anti-aging tablet group and the metformin group can effectively reduce the blood sugar level after 8 weeks of administration, the anti-aging tablet and the metformin group are better than the metformin group (P <0.01 and P < 0.05) in terms of reducing the blood sugar level of the rats with diabetes, and the combination of the anti-aging tablet and the metformin has a gain effect on reducing the blood sugar level of the rats with diabetes.
Example 2: anti-aging tablet and effect of combination of anti-aging tablet and metformin on liver tissue energy metabolism of type 2 diabetes rats
Taking and implementingIn example 1, 50mg of liver tissue of each group of male SD rats was added with 0.5mL of physiological saline, and the mixture was continuously ground on ice to prepare 10% (m/V) liver tissue homogenate, and after low-temperature centrifugation, the supernatant was aspirated for use. Detection of adenylate activating protein kinase (AMPK), na in liver tissue according to kit instructions + -K + -atpase, glycogen (GP) content.
Table 2 effects of anti-aging tablet and metformin in combination on liver tissue energy metabolism in type 2 diabetic rats
Comparison to the control group: △ P<0.05， △△ P<0.01; comparison to model set: * P<0.05， ** P<0.01; compared with the low dose group of anti-aging tablets: ▲ P<0.05， ▲▲ P<0.01; in comparison with the group of metformin, ※ P<0.05， ※※ P<0.01。
experimental results: the results of the effects on the liver tissue energy metabolism related indexes are shown in the table 2, and the experimental results find that AMPK and Na in the liver tissue of the rat in the model group + -K + -a significant decrease in ATPase, GP content (P<0.01 A) is provided; prognosis of administration of anti-aging tablet and metformin, AMPK, na + -K + -a significant increase in ATPase content (P)<0.05 However, the anti-aging patch had no significant effect on GP levels; compared with the single administration group, the anti-aging tablet and the metformin combination can obviously raise Na + -K + ATPase and GP content (P)<0.05). Experimental results show that the anti-aging tablet can improve the liver tissue energy metabolism disorder of the diabetic rat, and the anti-aging tablet has a gain effect on the relieving effect of the liver tissue energy metabolism disorder when being combined with the metformin.
Example 3: anti-aging tablet and effect of combination of anti-aging tablet and metformin on energy metabolism of myocardial tissue of type 2 diabetes rat
50mg of myocardial tissue of each group of male SD rats in example 1 was taken, 0.5mL of physiological saline was added, and the mixture was continuously ground on ice to prepare 10% (m/V) myocardial tissue homogenate, which was centrifuged at low temperature, and the supernatant was aspirated for use. The amounts of Adenosine Triphosphate (ATP), creatine Kinase (CK), lactate Dehydrogenase (LDH) and mitochondrial respiratory chain complexes I-IV (RCC I-IV) in myocardial tissue were measured according to the kit instructions.
TABLE 3 Effect of anti-aging tablets and metformin in combination on ATP, LDH, CK levels in myocardial tissue of type 2 diabetic rats
TABLE 4 Effect of anti-aging tablets and metformin in combination on RCC I-IV levels in myocardial tissue of type 2 diabetic rats
In tables 3-4 above, compared to the control: △ P<0.05， △△ P<0.01; comparison to model set: * P<0.05， ** P<0.01; compared with the low dose group of anti-aging tablets: ▲ P<0.05， ▲▲ P<0.01; in comparison with the group of metformin, ※ P<0.05， ※※ P<0.01。
experimental results: the results of the effect on the index related to myocardial tissue energy metabolism are shown in tables 3 and 4 above. The experimental result shows that compared with the control group, the ATP, LDH, RCC IV content in the myocardial tissue of the rats in the model group is obviously reduced (P < 0.01), and the CK content is obviously increased (P < 0.01); the content of ATP, LDH, RCC IV in myocardial tissue of the anti-aging tablet and metformin dry prognosis is obviously increased (P < 0.05) compared with that of a model group, and CK is obviously reduced (P < 0.01); the anti-aging tablet and the metformin combined have better effects on the indexes than the independent administration groups. The results show that the anti-aging tablet can improve the myocardial tissue energy metabolism disorder of the diabetic rats, and can synergistically regulate the myocardial tissue energy metabolism disorder by being combined with the metformin.
In conclusion, the invention utilizes the high-fat feed to feed and combines with STZ intraperitoneal injection to construct a type 2 diabetes rat model, reduces FBG and HbA1c levels of the diabetes rat after the anti-aging tablet is administrated, and improves myocardial tissue (ATP, CK, LDH, RCC I-IV) and liver tissue (AMPK, na) + -K + -atpase, GP) and in combination with metformin synergistically regulates diabetes-induced energy metabolism disorders.
The examples described above represent only a few embodiments of the present invention and are not intended to limit the embodiments. Various other modifications will be apparent to those skilled in the art to which the invention pertains based upon the teachings herein. The present invention need not and cannot be exhaustive of all embodiments. Obvious variations or modifications of the invention are therefore contemplated as falling within the scope of the present invention.
Claims (8)
1. The use of an anti-aging tablet in the preparation of a medicament for preventing and/or treating type 2 diabetes mellitus and/or energy metabolism disorders associated therewith in a mammal, wherein the raw material medicaments of the anti-aging tablet comprise radix rehmanniae, red ginseng, dwarf lilyturf tuber, asparagus root, cortex lycii radicis and poria cocos.
2. The use according to claim 1, wherein the anti-aging tablet is produced by zhengshenbao pharmaceutical industry limited.
3. The use of claim 1, wherein the anti-aging tablet reduces blood glucose and glycosylated hemoglobin (HbA 1 c) levels in a mammal having type 2 diabetes.
4. The use of claim 1, wherein the anti-aging patch modulates an energy metabolism-related index in mammalian heart muscle and liver tissue suffering from type 2 diabetes, wherein the energy metabolism-related index in heart muscle comprises Adenosine Triphosphate (ATP), creatine Kinase (CK), lactate Dehydrogenase (LDH), and mitochondrial respiratory chain complexes i-iv (RCC i-iv); the index related to energy metabolism in liver tissue comprises adenylate activating protein kinase (AMPK), na + -K + ATPase and Glycogen (GP).
5. Use of an anti-aging tablet in combination with metformin for the manufacture of a medicament for the prevention and/or treatment of type 2 diabetes mellitus and/or energy metabolism disorders associated therewith in a mammal.
6. The use of claim 5, wherein the anti-aging tablet in combination with metformin reduces blood glucose and HbA1c levels in mammals suffering from type 2 diabetes.
7. The use of claim 5, wherein the anti-aging tablet in combination with metformin modulates an energy metabolism-related index in myocardial and liver tissue of a mammal suffering from type 2 diabetes, wherein the energy metabolism-related index in the myocardium comprises ATP, CK, LDH and RCC i-iv; the related index of energy metabolism in liver tissue comprises AMPK and Na + -K + ATPase and GP.
8. The use according to any one of claims 1-7, wherein the mammal comprises a human, a rat, a mouse.
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