TW202000211A - Use of composition of Neoandrographolide for improving renal function - Google Patents

Abstract

The present invention provides the use of Neoandrographolide in preparing a composition for improving renal function. Neoandrographolide is the active component in the composition.

Description

Application of new andrographolide composition for improving renal function

The present invention relates to the use of neo-andrographolide, and particularly to the use of neo-andrographolide for preparing a composition for improving renal function.

Diabetes (Diabetes mellitus) is an increasingly serious problem that has caused financial problems and a decline in the quality of life of many citizens in developed and developing countries. Diabetes is characterized by patients with hyperglycemia, often accompanied by disorders of fat and protein metabolism. In general, without treatment, diabetes can cause many complications, such as cardiovascular disease, blindness, renal failure and peripheral nerve damage, etc., and even cause death in severe cases. According to the statistics of the World Health Organization (WHO), there are currently about 250 million people worldwide with diabetes, and by 2030, the number of patients is estimated to reach 360 million.

Diabetes can be divided into two types, including type 1 diabetes (insulin-dependent diabetes) and type 2 diabetes (non-insulin-dependent diabetes). Both types of diabetics are characterized by long-term blood glucose above standard values. In addition to insufficient or no secretion of insulin, insulin resistance is also considered to be one of the common causes of diabetes.

Andrographis paniculata (AP) is a promising genus of plants for the treatment of hyperglycemia, which is widely cultivated in India, China, Malaysia and Taiwan. The main medicinal parts of Andrographis paniculata are dry stems and leaves. Andrographis paniculata leaves contain a variety of diterpene lactone compounds, including Deoxyandrographolide, Andrographolide, Neoandrographolide, and Andrographolide. Ester (Homoandrographolide), Panicolide (Panicolide). It also contains Andrographan, Andrographon, Andrographosterin, β-sitosterol-D-glucoside and so on. In addition to andrographolide, the root also contains 5-hydroxy-7, 8, 2", 3"-tetramethoxyflavonoid (Mono-o-methylwithtin), 5-hydroxy-7, 8, 2"-trimethyl Andrographin, 5, 2"-dihydroxy-7, 8-dimethoxyflavone (Panicolin), apigenin-7, 4"-dimethyl ether (Apigenin-7, 4"-dimethyl ether) , A1-sitosterol and potassium dihydrogen phosphate (KH ₂ PO ₄ ), etc. According to preliminary analysis, Andrographis paniculata also contains phenolic substances such as sterol saponins, sugars and condensed tannins.

The various components of the Andrographis paniculata plant, especially whether the new andrographolide has specific medical and health care functions, is a topic worthy of further discussion and research.

The present invention provides new uses of new andrographolide, in particular, the use of new andrographolide for preparing a composition which can improve renal function. Experiments have found that neo-andrographolide has at least the ability to improve kidney function. In addition, New Andrographolide has the ability to simultaneously lower blood sugar, lower blood fat, improve liver function and improve kidney function.

The present invention discloses the use of neo-andrographolide in preparing a composition that can improve renal function, wherein the composition includes neo-andrographolide as an active ingredient, and the composition is used to reduce the user's creatinine index to improve Kidney clearance rate.

The present invention also discloses the use of neo-andrographolide to prepare a composition that can improve renal function, wherein the composition includes neo-andrographolide as an active ingredient, and the composition is used to reduce the user's uric acid index.

In an embodiment of the invention, the andrographolide included in the composition is the only active ingredient.

In an embodiment of the present invention, the minimum effective dose range of the neo-andrographolide is 0.5 mg/kg to 20 mg/kg.

In an embodiment of the present invention, the minimum effective dose range of the andrographolide is 0.625 mg/kg to 20 mg/kg.

In an embodiment of the invention, the user is a type 2 diabetes patient.

In an embodiment of the invention, the composition is a pharmaceutical composition.

In an embodiment of the invention, the composition is a preparation.

In an embodiment of the present invention, the formulation is a tablet, tablet, liquid, powder, granule, powder, pill, drip, capsule, ointment, cream, latex, gel, patch, injection , Inhalation, spray or suppository.

In an embodiment of the invention, the composition is an external preparation.

In an embodiment of the present invention, the external preparation includes liquid, powder, granule, spray, ointment, cream, latex, gel or patch.

In an embodiment of the invention, the composition is an oral preparation.

In an embodiment of the present invention, the oral preparation includes tablets, tablets, liquids, powders, granules, powders, pills, pills or capsules.

In an embodiment of the present invention, the composition is a pharmaceutical composition, and the composition further includes a carrier, diluent or excipient used in medicine as an inactive ingredient in the composition .

In an embodiment of the present invention, the composition is a food composition, and the composition further includes a flavor enhancer, sweetener, thickener or excipient used in the food as the composition Inactive ingredients.

The present invention also provides the use of a composition as a functional food for improving renal function. The composition includes an active ingredient composed of andrographolide; and a flavor enhancer, sweetener, thickener used in food Agents or excipients are used as inactive ingredients in the composition.

In an embodiment of the invention, the functional food is in the form of a liquid beverage, a jelly, a capsule, a lozenge, a tablet, or a powder.

Based on the above, the present invention provides a new use of new andrographolide, which is suitable for use in lowering blood sugar, lowering blood fat, improving liver function, and improving kidney function.

In order to make the above-mentioned features and advantages of the present invention more obvious and understandable, the embodiments are specifically described below in conjunction with the accompanying drawings for detailed description as follows.

化學式1。The neoandrographolide (Neoandrographolide) described in the embodiments of the present invention may include neoandrographolide extracted from the plant of Andrographis paniculata or neo-andrographolide synthesized by chemical synthesis. The chemical structural formula of new andrographolide is shown in the following chemical formula 1:

Chemical formula 1.

The new andrographolide described in the embodiments of the present invention includes its physiologically functional derivatives, that is to say, the new andrographolide described in the embodiments of the present invention includes its pharmaceutically acceptable salts, Its pharmaceutically acceptable enantiomers, its pharmaceutically acceptable solid form (crystalline, semi-crystalline or amorphous), its pharmaceutically acceptable polymorphs, its pharmacologically acceptable A pharmaceutically acceptable solvate or a pharmaceutically acceptable metabolite or pharmaceutically acceptable prodrug.

Some embodiments of the present invention provide the use of neo-andrographolide to prepare a composition that can improve renal function, and the composition includes neo-andrographolide as the only pharmacologically active ingredient. According to the embodiment of the present invention, the application of the composition can effectively reduce the creatinine index of the applicator (ie, user) to improve the renal clearance rate. According to the embodiment of the present invention, the application of the composition can effectively reduce the user's uric acid index. Through the above-mentioned various applications, the use of the composition can more effectively achieve the purpose of improving renal function for users. In some other embodiments, neoandrographolide is the main active ingredient in the composition, but it can still be used together with other active ingredients to achieve the purpose of improving renal function.

In some embodiments, when neo-andrographolide is used to reduce the creatinine index of the user to improve the renal clearance rate, the applicable dose is 0.5 mg/kg to 20 mg/kg. In other words, the lowest effective dose is about 0.5 mg/kg. In some embodiments, the effective dosage range of neoandrographolide is 0.625 mg/kg to 20 mg/kg. In some embodiments, the effective dosage range of neoandrographolide is 0.625 mg/kg to 10 mg/kg. In some embodiments, the effective dosage range of neoandrographolide is 0.625 mg/kg to 5 mg/kg. In another embodiment, when neo-andrographolide is used to reduce the uric acid index of the user, the applicable dose is 0.5 mg/kg to 20 mg/kg. In other words, the lowest effective dose is about 0.5 mg/kg. In some embodiments, the effective dosage range of neoandrographolide is 0.625 mg/kg to 20 mg/kg. In some embodiments, the effective dosage range of neoandrographolide is 0.625 mg/kg to 10 mg/kg. In some embodiments, the effective dosage range of neoandrographolide is 0.625 mg/kg to 5 mg/kg. In some embodiments of the present invention, andrographolide is the only active ingredient in the composition. In other words, in some embodiments of the present invention, the composition of the present example only uses new andrographolide as the pharmacologically active ingredient in the composition of the present example, and other ingredients contained in the andrographis paniculata extract, such as deoxyandrographolide ( Deoxyandrographolide) and Andrographolide are not included in the composition of the examples in this case.

In some embodiments, the composition is a pharmaceutical composition or a preparation. In some embodiments, the preparation may be an oral preparation or an external preparation, but it is not limited thereto. In some embodiments, the formulation is a tablet, tablet, liquid, powder, granule, powder, pill, drop, pill, capsule, ointment, cream, latex, gel, patch, injection , Inhalation, spray or suppository, etc. In some embodiments, the oral formulation refers to oral administration or may be suitable for oral administration. For the purposes of the present invention, oral dosage forms include capsules, lozenges, pills, granules, powders, drops, and pills. For example, the preparation may be coated or uncoated, foamed, soluble, orally disintegrating, enteric-coated or sustained-release tablets; sugar-coated tablets; hard capsules; soft capsules; granular forms; pills; The composition is formulated in the form of tablets. Preferably, the oral preparation is in the form of tablets or capsules. In some embodiments, the external preparation is a liquid, powder, granule, spray, ointment, cream, latex, gel, or patch.

In some embodiments, the composition is a health food composition, a functional food composition, a functional health food composition, or even a food composition that can be used as a food composition to prevent physiological function changes or a food composition that changes appearance Wait, but not as a limitation. In some embodiments, the food composition further includes additives, carriers, diluents or excipients as other inactive ingredients in the composition. The carrier, diluent or excipient is not particularly limited, and can be adjusted in accordance with different composition types or dosage forms. For example, additives and excipients include but are not limited to anti-sticking agents, anti-foaming agents, buffers, polymers, antioxidants, preservatives, chelating agents, viscosity modifiers, tonicity modifiers, flavoring agents, coloring Agents, fragrances, opacifiers, suspending agents, adhesives, fillers, plasticizers, lubricants and mixtures thereof. In some embodiments, the composition further includes flavoring agents, sweeteners, thickeners, or excipients used in food as inactive ingredients in the composition.

In some embodiments, the functional food for improving renal function may use a composition consisting of neo-andrographolide or a composition containing neo-andrographolide as the main active ingredient. In some embodiments, the functional food may be in the form of a liquid beverage, a jelly, a capsule, a lozenge, a tablet, or a powder, but it is not limited thereto. For example, the functional food may be any functional food that can be taken or consumed by oral administration.

For the application and efficacy of the new andrographolide in the embodiments of the present invention, the following embodiments will be taken as examples. However, the following examples are only for illustrative purposes, and are not intended to limit the present invention. Examples

In this example, the effects of various doses of new andrographolide on the blood glucose regulation ability, physiological function, blood biochemical substances and pathology of some important organs and tissues of the induced group (induced type 2 diabetic mice) will be tested. Impact assessment.

Male ICR mice (19-21 g) were purchased from Taiwan BioLASCO Co., Ltd. The mice were fed in the animal center of Universal University of Technology, the temperature was controlled at 22 ± 2°C, the relative humidity was 55 ± 5%, and a 12-hour light/12-hour dark cycle was applied one week before the experiment. For the induction of type II diabetic rats (induction treatment group STZ), nicotine amide (Nicotinamide; Sigma, Saint Louis, MO, USA) saline solution (210 mg/kg bw) was injected intraperitoneally into mice, After 15 minutes, streptozotocin (STZ) (Sigma, 180 mg/kg bw, ip injection) dissolved in citrate buffer (pH 4.5) will be administered to the mice before use. The control group received those two carriers. During the experiment, the food intake and body weight of the experimental animals were recorded once a week. In addition, the dosage of the new andrographolide (Sigma-Aldrich Chemical Co., Missouri, USA) of the present invention is: NeoL (new andrographolide low-dose group): new andrographolide 2.5mg/kg; NeoM (new andrographolide) Medium-dose lactone group): Neo-Andrographolide 5.0mg/kg; NeoH (New andrographolide high-dose group): Neo-Andrographolide 10 mg/kg. The above active ingredient is dissolved in Tween 20 and adjusted to a 0.5% methyl cellulose (CMC) solution. The blank group (Sham) is normal mice without induction treatment. Clinical Observation

Observe the animal's physical condition at least twice a day, and the interval between each observation is not less than 6 hours to determine the animal's health or death status. Observe the clinical signs of the test animals at least once a day, and record the toxic effects exhibited by the test animals, including the start time and process of such toxic effects. After the test, the surviving mice were sacrificed; afterwards, autopsy was performed and blood samples were taken for serum biochemical analysis. Water intake testing

Generally speaking, people with diabetes usually have clinical symptoms of "drinking more water". In this experimental example, the blank group Sham, the induction treatment group STZ, neo-andrographolide low-dose group NeoL (2.5 mg/kg), neo-andrographolide mid-dose group NeoM (5.0 mg) were recorded in a 40-day period /kg) and the water intake of NeoH (10mg/kg) mice in the high-dose group of andrographolide. The experimental results are shown in Figure 1.

Fig. 1 shows the results of water intake of various types of andrographolide in the experimental group of the present invention on mice with type 2 diabetes in the induced group. As shown in FIG. 1, the water intake of the STZ mice in the induction treatment group was significantly higher than that of the Sham mice in the blank group during the 40-day period. The results of this experiment prove that the water intake of induced type 2 diabetic mice will be much higher than that of normal mice. In addition, when the induced type 2 diabetic mice were administered different doses of andrographolide, the experimental results found that whether at high dose (10mg/kg) or low dose (2.5mg/kg) , The water consumption of the induced type II diabetic mice will be significantly reduced. In other words, neoandrographolide can be used alone as an active ingredient to alleviate the clinical symptoms of diabetic mice. Oral glucose tolerance test

In this experimental example, an oral glucose tolerance test was conducted to assess peripheral glucose utilization. In the neo-andrographolide low-dose group NeoL (2.5 mg/kg), neo-andrographolide medium-dose group NeoM (5.0 mg/kg) and neo-andrographolide high-dose group NeoH (10 mg/kg) administered for 30 minutes Afterwards, a blood sample is collected before glucose administration to measure the blood glucose concentration in the sample, which is the blood glucose value at 0 hours. After giving glucose (2 g/kg) for 30, 60, 90, 120, 150, and 180 minutes, a blood sample was collected to measure the blood glucose concentration in the sample. The experimental results are shown in Figure 2.

FIG. 2 shows the results of oral glucose tolerance test of various dosages of andrographolide on the type 2 diabetic mice in the induced group of the experimental example of the present invention. In Figure 2, each value is expressed as an average value ± SEM (mean standard error), where ^### P<0.001 is compared to the blank group Sham; *P<0.05, **P<0.01, ***P <0.001 is compared to STZ in the induction treatment group. As shown in the experimental results of FIG. 2, the blood glucose value of STZ mice in the induction treatment group was significantly higher than that of the blank group Sham. The results of this experiment prove that the induced glucose tolerance of type 2 diabetic mice is worse than that of normal mice. In addition, the three-dose group (NeoL, NeoM, NeoH) of the new andrographolide (NeoL, NeoM, NeoH) had significantly lower blood glucose values within 0 to 3 hours than the STZ in the induction treatment group. The new andrographolide of the present invention can be used to improve the low glucose tolerance of induced type 2 diabetic mice. In other words, the new andrographolide of the present invention can be used to improve glucose tolerance in induced diabetic mice. Fasting blood glucose measurement

In this experimental example, the blank group Sham, the induction treatment group STZ, the neo-andrographolide low-dose group NeoL (2.5 mg/kg), the neo-andrographolide mid-dose group NeoM (5.0 mg) were recorded during the 42-day period /kg) and the fasting blood glucose values of NeoH mice in the new high-dose andrographolide group. The experimental results are shown in Figure 3.

Fig. 3 shows the results of determination of fasting blood glucose levels of type 2 diabetes mice in the induced group with various doses of andrographolide in the experimental example of the present invention. In Figure 3, each value is expressed as an average value ± SEM (mean standard error), where ^### P<0.001 is compared to the blank group Sham; *P<0.05, **P<0.01, ***P <0.001 is compared to STZ in the induction treatment group. As shown in the experimental results of FIG. 3, the fasting blood glucose values of STZ mice in the induction treatment group were significantly higher than those in the blank group from 0 to 42 days. The results of this experiment prove that the induced glucose tolerance of type 2 diabetic mice is worse than that of normal mice. In addition, the fasting blood glucose values of the three dose groups of neo-Andrographolide (NeoL, NeoM, NeoH) after the seventh day of administration were significantly lower than those of the induction treatment group STZ. In other words, the novel andrographolide of the present invention can be used to reduce the fasting blood glucose value of induced diabetic mice. From the experimental point of view, the novel andrographolide of the present invention can be used to reduce the fasting blood glucose value and improve the problem of induced blood glucose rise in type 2 diabetic mice. And from the current experimental minimum effective dose range of 2.5mg/kg to 10mg/kg, the three dose groups of neo-andrographolide (NeoL, NeoM, NeoH) are quite effective. Linear extrapolation predicts that the lowest effective dose that may be applicable may be in the range of 0.5 mg/kg to 20 mg/kg or 0.625 mg/kg to 20 mg/kg. Determination of glycated hemoglobin ( HbA1c )

"Glycated hemoglobin" (HbA1c) means that the red blood cells in the human blood contain hemoglobin. When glucose in the blood enters the red blood cells and combines with heme, glycated hemoglobin is formed. Generally, the average life span of red blood cells is 120 days. Glucose is not easy to fall off when attached to hemoglobin. Therefore, checking the concentration of glycated hemoglobin in the blood can reflect the blood glucose control in the body for the last 2-3 months. The biggest difference between HbA1C and blood glucose is that the blood glucose value only represents the blood glucose state at the time of blood draw, and the blood glucose control situation for a longer period of time must be reflected by HbA1C. HbA1C is an excellent indicator for detecting early diabetes. These patients have a milder condition. The slightly higher blood sugar often returns to the normal range after a period of starvation. Therefore, when measuring blood sugar on an empty stomach, such patients are often missed. However, HbA1C has no This shortcoming In 2009, the American Diabetes Association proposed to use "glycated hemoglobin" >= 6.5% as the diagnostic criteria for diabetes. Therefore, in addition to being used as a blood glucose tracking index for diabetes, "glycated hemoglobin" is also a new diagnostic tool. HbA1C (glycated hemoglobin) has been widely used in diabetic patients who need to monitor blood glucose in recent years. It can reflect the blood glucose control status about one month before blood collection, and can be used to monitor the situation of blood glucose control, and can also be used as an adjustment. The basis of the dose.

In this experimental example, the blank group Sham, induction treatment group STZ, neo-andrographolide low-dose group NeoL (2.5 mg/kg), neo-andrographolide medium-dose group NeoM (5.0 mg/ kg) and the value of glycated hemoglobin (HbA1c) in NeoH mice in the new high-dose andrographolide group. The experimental results are shown in Figure 4.

Fig. 4 shows the results of the effects of various doses of andrographolide on the glycated hemoglobin (HbA1c) of type 2 diabetic mice in the experimental group of the present invention. In FIG. 4, each value is expressed as an average value ± SEM (mean standard error), where ^### P<0.001 is compared to the blank group Sham; ***P<0.001 is compared to the induction treatment group STZ. As shown in the experimental results of Figure 4, the STZ mice in the induction treatment group had significantly higher HbA1c values after 42 days than the blank group Sham. The results of this experiment prove that the blood glucose control of the induced type 2 diabetic mice is worse than that of normal mice. In addition, after 42 days of continuous administration, the HbA1c values of the three dose groups of neo-andrographolide (NeoL, NeoM, NeoH) were significantly lower than those of the induction treatment group STZ. In other words, the novel andrographolide of the present invention can be used to improve the problem of poor blood glucose control in induced type 2 diabetic mice. And from the current experimental minimum effective dose range of 2.5mg/kg to 10mg/kg, the three dose groups of neo-andrographolide (NeoL, NeoM, NeoH) are quite effective. Linear extrapolation predicts that the lowest effective dose that may be applicable may be in the range of 0.5 mg/kg to 20 mg/kg or 0.625 mg/kg to 20 mg/kg. Determination of glutamate phenylacetate aminotransferase ( Aspartate Aminotransferase ; AST )

In general, non-alcoholic fatty liver is common in patients with type 2 diabetes, which is likely to cause liver cell damage and liver function decline. Aspartate Aminotransferase (AST) is an enzyme mainly found in liver, heart muscle, skeletal muscle and red blood cells. When liver cells are destroyed or damaged, AST enzymes are released and enter the bloodstream. Therefore, blood tests can tell whether liver function is affected.

In this experimental example, the blank group Sham, induction treatment group STZ, neo-andrographolide low-dose group NeoL (2.5 mg/kg), neo-andrographolide medium-dose group NeoM (5.0 mg/ kg) and the AST index of NeoH mice in the new high-dose andrographolide group. The experimental results are shown in Figure 5.

FIG. 5 shows the effect of various doses of andrographolide on the glutamate phenylacetate transaminase (AST) index of type 2 diabetic mice in the experimental group of the present invention. In Figure 5, the average value of each Zhi ± SEM (standard error of the mean) is represented, where ^# P <0.05 compared to the control group is Sham; * P <0.05 was induced by treatment group compared to STZ. As shown in the experimental results of Figure 5, the STZ mice in the induction treatment group had significantly higher AST values after 42 days than the blank group Sham. The results of this experiment prove that the induced liver function of type 2 diabetic mice is significantly worse than that of normal mice. In addition, after 42 days of continuous administration, the AST values of the three dose groups (NeoL, NeoM, NeoH) of neo-andrographolide were slightly lower than those of the induction treatment group STZ. Among them, the AST value of NeoL (2.5 mg/kg) in the low-dose group of andrographolide decreased most significantly. The experimental results show that the new andrographolide of the present invention has the effect of improving liver function, and the lowest effective dose is judged to be 2.5mg/kg, and the lowest effective dose that may be applicable by linear extrapolation is 1.25 Between mg/kg and 10mg/kg. Determination of triglyceride ( triglyceride ) and total cholesterol ( cholesterol )

Clinically, as many as 6 to 8 percent of diabetes patients will have hypertension and hyperlipidemia. The mechanism of diabetes combined with hyperlipidemia is more complicated. The most common types include increased blood triglycerides, decreased high-density lipoprotein cholesterol (HDL-C) and increased low-density lipoprotein cholesterol (LDL-C). Therefore, for diabetic patients, the monitoring of triglycerides and total cholesterol is also extremely important.

In this experimental example, the blank group Sham, induction treatment group STZ, neo-andrographolide low-dose group NeoL (2.5 mg/kg), neo-andrographolide medium-dose group NeoM (5.0 mg/ kg) and the triglyceride and total cholesterol in NeoH mice of the new andrographolide high-dose group. The experimental results are shown in Figure 6 and Figure 7.

FIG. 6 shows the effect of various doses of andrographolide on the triglyceride value of type 2 diabetic mice in the experimental group of the present invention. In Figure 6, each value is expressed as an average value ± SEM (mean standard error), where ^## P<0.01 is compared to the blank group Sham; **P<0.01, ***P<0.001 is compared to Induction treatment group STZ. As shown in the experimental results of FIG. 6, the STZ mice in the induction treatment group had significantly higher blood triglyceride values after 42 days than the blank group Sham. The results of this experiment prove that the induced type 2 diabetic mice have high blood lipids and high cholesterol. In addition, after 42 days of continuous administration, the triglyceride values of the three dose groups of neo-andrographolide (NeoL, NeoM, NeoH) were lower than those of the induction treatment group STZ. Among them, the neo-andrographolide medium-dose group NeoM (5.0 mg/kg) and the neo-andrographolide high-dose group NeoH (10 mg/kg) had the lowest triglyceride values. The experimental results show that the new andrographolide of the present invention has a triglyceride-reducing effect and has a dose-dependent effect, and its minimum effective dose is 2.5 mg/kg.

FIG. 7 shows the results of the effects of various doses of new andrographolide on the total cholesterol in the blood of the induced type 2 diabetic mice in the experimental example of the present invention. In FIG. 7, each value is expressed as an average value ± SEM (mean standard error), where ^### P<0.001 is compared to the blank group Sham; *P<0.05 is compared to the induction treatment group STZ. As shown in the experimental results of FIG. 7, the total cholesterol in the blood of STZ mice in the induction treatment group after 42 days was significantly higher than that in the blank group Sham. The results of this experiment prove that the induced type 2 diabetic mice have high blood lipids and high cholesterol. In addition, after 42 days of continuous administration, the total cholesterol values of the three dose groups of Neo-Andrographolide (NeoL, NeoM, NeoH) were slightly lower than that of the induction treatment group STZ, showing that Neo-Andrographolide improved the total cholesterol in the blood. Effect, and its lowest effective dose is 2.5mg/kg. Serum uric acid (Uric Acid) assay

Many studies have found that the high risk factors for type 2 diabetes and high uric acid are the same. Among them, the most obvious are overweight and obesity. Type 2 diabetes and high uric acid not only have the same etiology, too much uric acid can increase the risk of type 2 diabetes, so reducing the level of uric acid in the blood can prevent the incidence of type 2 diabetes. There are many causes of excessive uric acid in the human body. For example, dietary content, weight, exercise, taking drugs, genetics and other factors may cause hyperuricemia. Most of the uric acid in the blood is excreted by the kidneys. Once the uric acid value increases, the concentration in the kidneys will also increase, it is easy to produce uric acid crystals and precipitate in the kidneys, causing kidney damage. Therefore, hyperuricemia is likely to cause a decline in renal function.

In this experimental example, the blank group Sham, induction treatment group STZ, neo-andrographolide low-dose group NeoL (2.5 mg/kg), neo-andrographolide medium-dose group NeoM (5.0 mg/ kg) and the serum uric acid index of NeoH mice in the high-dose group of neo-andrographolide. The experimental results are shown in Figure 8.

FIG. 8 shows the effect of various doses of andrographolide on the serum serum uric acid index of type 2 diabetic mice in the induced group in the experimental example of the present invention. In Figure 8, each value is expressed as an average value ± SEM (mean standard error), where ^### P<0.001 is compared to the blank group Sham; **P<0.01, ***P<0.001 is compared In the induction treatment group STZ. As shown in the experimental results of FIG. 8, the serum uric acid index of STZ mice in the induction treatment group after 42 days was significantly higher than that of the blank group Sham. The results of this experiment prove that the induced type 2 diabetic mice have hyperuricemia. In addition, after 42 days of continuous administration, the three dose groups of neo-andrographolide (NeoL, NeoM, NeoH) had significantly lower serum uric acid indexes than the induction treatment group STZ. The experimental results show that the new andrographolide of the present invention can reduce the uric acid index of patients with hyperuricemia and achieve the effect of improving renal function. In addition, from the current experimental minimum effective dose range of 2.5mg/kg to 10mg/kg, the three dose groups of neo-andrographolide (NeoL, NeoM, NeoH) are quite effective. Linear extrapolation predicts that the lowest effective dose that may be applicable may be in the range of 0.5 mg/kg to 20 mg/kg, or between 0.625 mg/kg and 20 mg/kg serum creatinine ( serum creatinine ) determination

Diabetic nephropathy is one of the important complications of diabetes and often leads to the death of patients. When the kidney disease progresses to a later stage, its filtering function will be gradually damaged, resulting in the inability to clean up harmful substances such as creatinine, which in turn causes the rise of creatinine, and finally leads to kidney failure. Detecting the patient's serum creatinine concentration can be used to determine whether the renal function is affected.

In this experimental example, the blank group Sham, induction treatment group STZ, neo-andrographolide low-dose group NeoL (2.5 mg/kg), neo-andrographolide medium-dose group NeoM (5.0 mg/ kg) and the serum creatinine index of NeoH mice in the new high-dose andrographolide group. The experimental results are shown in Figure 9.

FIG. 9 shows the effect of various doses of andrographolide on the serum creatinine index of type 2 diabetic mice in the experimental group of the present invention. In Figure 9, the numerical average Zhi ± SEM (standard error of the mean) is represented, where ^# P <0.05 compared to the control group is Sham; *** P <0.001 compared to the process of induction is set STZ. As shown in the experimental results of FIG. 9, the serum creatinine index of STZ mice in the induction treatment group after 42 days was significantly higher than that of the blank group Sham. The results of this experiment prove that the renal clearance rate of induced type 2 diabetic mice is reduced by the influence of the inducing drug. In addition, after 42 days of continuous administration, the serum creatinine index of the three dose groups (NeoL, NeoM, NeoH) of neo-andrographolide was significantly lower than that of the induction treatment group STZ. The results of this experiment show that the new andrographolide of the present invention can reduce the elevated effect of serum creatinine in patients, thereby achieving the function of protecting the kidney. In addition, from the current experimental minimum effective dose range of 2.5mg/kg to 10mg/kg, the three dose groups of neo-andrographolide (NeoL, NeoM, NeoH) are quite effective. Linear extrapolation predicts that the lowest effective dose that may be applicable may be in the range of 0.5 mg/kg to 20 mg/kg or 0.625 mg/kg to 20 mg/kg.

In summary, the experimental results of the present invention found that neo-andrographolide alone can improve glucose tolerance, reduce fasting blood glucose and glycated hemoglobin HbA1C in induced type 2 diabetic mice, showing its use for lowering blood glucose. Neoandrographolide alone can reduce the AST value of induced type 2 diabetic mice, showing that it has the purpose of improving liver function. Neo-Andrographolide alone can improve the triglycerides and total cholesterol in blood of induced type 2 diabetic mice, showing the use of its hypotensive esters. In addition, andrographolide can independently improve the serum uric acid index and serum creatinine index of induced type 2 diabetic mice, showing that it has the purpose of improving renal function.

Although the present invention has been disclosed as above with examples, it is not intended to limit the present invention. Any person with ordinary knowledge in the technical field can make some changes and modifications without departing from the spirit and scope of the present invention. The scope of protection of the present invention shall be subject to the scope defined in the appended patent application.

Sham‧‧‧Blank group STZ‧‧‧Induction treatment group NeoL‧‧‧New andrographolide low-dose group NeoM‧‧‧New andrographolide medium-dose group NeoH‧‧‧New andrographolide high-dose group

Fig. 1 shows the results of water intake of various types of andrographolide in the experimental group of the present invention on mice with type 2 diabetes in the induced group. FIG. 2 shows the results of oral glucose tolerance test of various dosages of andrographolide on the type 2 diabetic mice in the induced group of the experimental example of the present invention. Fig. 3 shows the results of fasting blood glucose measurement of various doses of andrographolide in the experimental group of the present invention on the induced type 2 diabetic mice. Fig. 4 shows the results of the effects of various doses of andrographolide on the glycated hemoglobin (HbA1c) of type 2 diabetic mice in the experimental group of the present invention. FIG. 5 shows the effect of various doses of andrographolide on the glutamate phenylacetate transaminase (AST) index of type 2 diabetic mice in the experimental group of the present invention. FIG. 6 shows the effect of various doses of andrographolide on the triglyceride value of type 2 diabetic mice in the experimental group of the present invention. Fig. 7 shows the results of the effects of various doses of new andrographolide on the total cholesterol in the blood of the induced type 2 diabetic mice in the experimental example of the present invention. FIG. 8 shows the effect of various doses of andrographolide on the serum serum uric acid index of type 2 diabetic mice in the induced group in the experimental example of the present invention. FIG. 9 shows the effect of various doses of andrographolide on the serum creatinine index of type 2 diabetic mice in the experimental group of the present invention.

Sham‧‧‧ Blank

STZ‧‧‧Induction treatment group

NeoL‧‧‧New andrographolide low-dose group

NeoM‧‧‧New Andrographolide Medium Dose Group

NeoH‧‧‧New andrographolide high-dose group

Claims (20)

The use of neo-andrographolide in the preparation of a composition that can improve renal function, wherein the composition includes neo-andrographolide as an active ingredient, and the composition is used to reduce the user's creatinine index to improve renal clearance . The use of neo-andrographolide for preparing a composition for improving renal function, wherein the composition includes neo-andrographolide as an active ingredient, and the composition is used to reduce the uric acid index of the user. The use as described in item 1 or item 2 of the scope of patent application, wherein the andrographolide included in the composition is the only active ingredient. The use as described in item 1 or item 2 of the patent application scope, wherein the minimum effective dosage range applicable to the new andrographolide is 0.5 mg/kg to 20 mg/kg. The use as described in item 1 or item 2 of the patent application scope, wherein the minimum effective dose range applicable to the new andrographolide is 0.625 mg/kg to 20 mg/kg. The use as described in item 1 or 2 of the patent application, wherein the user is a type 2 diabetes patient. The use as described in item 1 or item 2 of the patent application scope, wherein the composition is a pharmaceutical composition. The use as described in item 1 or item 2 of the patent application scope, wherein the composition is a preparation. The use as described in item 8 of the patent application range, wherein the formulation is a tablet, tablet, liquid, powder, granule, powder, pill, drip, capsule, ointment, cream, latex, gel, Patch, injection, inhalation, spray or suppository. The use as described in item 1 or item 2 of the patent application scope, wherein the composition is an external preparation. The use according to item 10 of the patent application scope, wherein the external preparation includes liquid, powder, granule, spray, ointment, cream, latex, gel or patch. The use as described in item 1 or item 2 of the patent application, wherein the composition is an oral preparation. The use as described in Item 12 of the patent application range, wherein the oral preparations include tablets, tablets, liquids, powders, granules, powders, pills, drops, or capsules. The use as described in Item 3 of the patent application scope, wherein the composition is a pharmaceutical composition, and the composition further includes a carrier, diluent or excipient used in medicine as the composition Of inactive ingredients. The use as described in item 3 of the patent application scope, wherein the composition is a preparation. The use as described in item 3 of the patent application scope, wherein the composition is an external preparation. The use according to item 3 of the patent scope, wherein the composition is an oral preparation. The use as described in item 1 or item 2 of the patent application scope, wherein the composition is a food composition, and the composition further includes flavoring agents, sweeteners, thickeners or The excipient serves as an inactive ingredient in the composition. Use of a composition as a functional food for improving renal function, the composition comprising an active ingredient composed of neo-andrographolide; and a flavor enhancer, sweetener, thickener or excipient used in food The agent serves as an inactive ingredient in the composition. The application as described in item 19 of the patent application scope, wherein the functional food is in the form of a liquid beverage, a jelly, a capsule, a lozenge, a tablet, or a powder.

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