KR101792834B1 - Combination of Pinitol and Natural Product for Treating Diabetes Mellitus - Google Patents

Abstract

(I) a first component component selected from the group consisting of: pinitol; And (ii) at least one natural substance selected from the group consisting of myoinositol, folic acid, banyan seed extract, and maltodextrin, as a second ingredient, to a kit for the treatment or prevention of diabetes mellitus. According to the combination kit of the present invention, the same or better diabetic therapeutic efficacy can be obtained while greatly reducing the dose of expensive pinitol, and the adverse effects due to the use of the anti-diabetic drug can be greatly reduced. In addition, the therapeutic efficacy of diabetes can be obtained more rapidly.

Description

[0002] Combination of Pinitol and Natural Product for Treating Diabetes Mellitus,

The present invention relates to a combination of pinitol and natural products for the treatment of diabetes.

Insulin resistance is closely related to diabetes, with occasional onset with little time difference, and in some cases, progression to diabetes followed by insulin resistance. Insulin resistance means that insulin does not function properly. Insulin secretion works properly. However, insulin secretion keeps the beta cells of the pancreas secreted by inserting a signal that the glucose in the blood enters the cell, . The accumulation of insulin in the blood does not send glucose-related signals, but by actively signaling the process of fat cell production that makes the body obese, many people with insulin resistance become obese. This leads to diabetes and other metabolic syndrome. At the insulin resistance stage, the beta cells of the pancreas continue to secrete more insulin than usual, according to the brain 's instructions, but eventually become tired and ultimately the beta cells are destroyed and the insulin production is greatly reduced. This is the period when diabetes develops in earnest and it is a time when symptoms of diabetes such as fatigue, thirst, hunger, and polyuria become clear.

Most drugs prescribed to patients with diabetes have the ability to inhibit rapid blood sugar increases and stimulate the pancreas to promote insulin secretion. However, in diabetic patients, the functions of drugs that promote insulin secretion are limited in cases where many cells of the pancreas are destroyed and fail to function. Therefore, most of the existing drugs are limited to the rapid inhibition of blood glucose increase. Conventional diabetic medications have relatively low and rapid blood glucose lowering functions, but various side effects (diarrhea, headache, fuzziness, nausea, etc.) have been reported. In addition, it has the function of promoting insulin secretion, but insulin is secreted in very little amount because the pancreas does not function normally in already advanced diabetes.

In this situation, pinitol, a natural substance extracted from soybean plants, has emerged as a substitute for the signaling function of insulin in order to complement the limited function of existing drugs and to eliminate side effects. Phenitol is a substance derived from inositol. Inositol is a substance found mainly in plants, and has many stereoisomers and optical isomers. The official name of pinitol is 3-O-methylation of d-chiro-inositol. It is mainly produced in pine, alfalfa and soybean plants. Pinitol induces creatine production in muscles and is reported to function as insulin. In addition, a number of studies have shown that it is effective in many diseases such as cancer, immunity, antimicrobials, and heart disease, and has a bactericidal effect against various pathogens. Pinitol can be used to prevent obesity and essential diabetes by taking it early in insulin resistance. Even if diabetic patients whose insulin levels are extremely reduced, insulin secretory function can be faithfully performed with only a small amount of insulin in the body There is an advantage in that it helps you to do. However, it is pointed out that pinitol is expensive to extract as a natural product and it takes at least 3-5 months to confirm the effect.

Numerous papers and patent documents are referenced and cited throughout this specification. The disclosures of the cited papers and patent documents are incorporated herein by reference in their entirety to better understand the state of the art to which the present invention pertains and the content of the present invention.

The present inventors have made efforts to develop a combination preparation which can more efficiently treat diabetes by administering concomitant use of pinitol and other natural products. As a result, it has been found that administration of the combination of pinitol and conventional natural products can reduce the dosage of expensive pinitol while achieving a synergistic therapeutic effect, can achieve the antidiabetic effect in a short time, reduce the side effect of the drug for diabetes treatment And the present invention has been completed.

Accordingly, an object of the present invention is to provide a combination kit of ingredients for the treatment or prevention of diabetes comprising pinitol and a natural product.

The objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims and drawings.

According to one aspect of the present invention, the present invention provides a composition comprising (i) a first component component selected from the group consisting of: pinitol; And (ii) at least one natural product selected from the group consisting of myoinositol, folic acid, banyan seed extract, and maltodextrin as the second component.

The combination kit of the present invention has a synergistic effect of treating or preventing diabetes by the combination of the first component and the second component, and reduces side effects of the diabetes therapeutic drug.

Pinitol

The present invention is based on the finding that the first component D-pinitol (3-O-methyl-D-chiro-inositol, Formula 1) can be extracted from pine, alfalfa, leguminous plants, (WO / 9629063), which induces the production of creatine in muscles, has therapeutic effects on immune diseases, heart diseases, and has antimicrobial efficacy.

The dose of pinitol in the combination kit of the present invention is 400 to 800 mg / day, preferably 450 to 750 mg / day, more preferably 500 to 700 mg / day, and most preferably 600 mg / One day.

Myo-inositol

The combination kit of the present invention comprises, as a second component, myo-inositol. Inositol or cyclohexane-1,2,3,4,5,6-hexol is a compound of a polyol having the formula C6H12O6 and having six alcohols of cyclohexane. Inositol can exist in the form of nine possible stereoisomers, of which the most prevalent form in nature is the form of myo-inositol. Myoinositol is a very important compound in providing a basic structural basis for many secondary messengers in signal transduction systems in eukaryotic cells.

In the combination kit of the present invention, the dose of myoinositol is 400 to 800 mg / day, preferably 450 to 750 mg / day, more preferably 500 to 700 mg / day, and most preferably 600 mg / 1 day.

Folic acid

The combination kit of the present invention contains, as a second component, folic acid. Folic acid is a type of vitamin, also called vitamin B9 or vitamin M. Because it is important for fetal nerve and vascular development, it is recommended for pregnant women before and during pregnancy.

The dose of folic acid in the combination kit of the present invention is 0.01 to 1000 μg / day, preferably 0.1 to 500 μg / day, more preferably 1 to 100 μg / day, and most preferably 50 μg / One day.

Centipede

The combination kit of the present invention comprises, as a second component, a perennial plant extract. It is said to be effective in boils, burns, swelling, asthma, bronchial asthma, sputum and pertussis in the private sector, and it is known to have constipation and ulcers. It is also known to mitigate the effect. It has also been reported that the fruit of the perennial plant has an ingredient having a wound healing (Fitoterpia, 2001; 72: 165 ~ 167) or an antiinflammatory effect (Fitoterpia, 2001; 72: 288-290). The perennial herb extract used in the present invention is an extract obtained from the stem, the fruit or the root portion of the perennial plant.

In the combination kit of the present invention, the dose of the perennial plant is 0.001 to 100 g / day, preferably 0.01 to 100 g / day, more preferably 0.1 to 50 g / day, most preferably 1 g / One day.

Maltodextrin

The combination kit of the present invention comprises, as a second component, maltodextrin. Maltodextrin is a polysaccharide substance used as a food additive. It is known that maltodextrin in maltodextrin inhibits absorption of sugars and is effective in controlling postprandial blood glucose. In addition, it is known that the gel is formed with high water retention that absorbs water to induce the feeling of fullness of the stomach, which is also helpful for controlling the food amount and weight loss. It is also known that it affects the improvement of lipid metabolism and energy metabolism, thereby reducing the absorption of fat into the body, and suppressing the formation and accumulation of body fat.

The dose of maltodextrin in the combination kit of the present invention is 0.001 to 100 g / day, preferably 0.01 to 100 g / day, more preferably 0.1 to 50 g / day, most preferably 7.5 g / 1 day.

(I) a first component component selected from the group consisting of: pinitol; And (ii) at least one natural substance selected from the group consisting of myoinositol, folic acid, banyan seed extract, and maltodextrin, as a second ingredient, to a kit for the treatment or prevention of diabetes mellitus. According to the combination kit of the present invention, the same or better diabetic therapeutic efficacy can be obtained while greatly reducing the dose of expensive pinitol, and the adverse effects due to the use of the anti-diabetic drug can be greatly reduced. In addition, the therapeutic efficacy of diabetes can be obtained more rapidly.

Figure 1 shows the results of insulin analysis in the blood collected during the first study period.
FIG. 2 shows the results of blood glucose analysis in the blood collected during the first study period.
FIG. 3 shows the results of analysis of HbA1c in the blood collected during the first study.
Figure 4 shows the results of analysis of fatty acids in the blood collected during the first study period.
Figure 5 shows the results of analysis of total cholesterol in the blood collected during the first study period.
Figure 6 shows the results of insulin analysis in the blood collected during the second study period.
Figure 7 shows the analysis of blood glucose in the blood collected during the second study period.
Figure 8 shows the results of analysis of HbA1c in the blood collected during the second study period.
Figure 9 shows the results of analysis of fatty acids in the blood collected during the second study period.
Figure 10 shows the results of analysis of total cholesterol in the blood collected during the second study period.
FIG. 11 shows the results of analyzing the change in blood glucose level in the blood collected 2 hours after the meal during the second study period.
Figure 12 shows the results of analyzing the change in fasting blood glucose during the second study period.

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are only for describing the present invention in more detail and that the scope of the present invention is not limited by these embodiments in accordance with the gist of the present invention .

Example

Example 1. Composition and amount of the combination preparation of pinitol

The pinitol combination preparations used in the present experiment are summarized in Table 1 below. Pinitol was purchased from Amikogen Co., and Baicin was purchased from Chungbuk Health & Medical Industry Center which processed Jeju Island acid. Mioinositol and folic acid were purchased from Sigma Company.

Complex type Composite composition Dose Remarks A Pinitol 1200 mg / day Existing research Pinitol
Compound preparation
B Pinitol + myoinositol 600 mg + 600 mg / day Price cheaper C Phenol + Folic Acid 600 mg + 50 μg / day High content of manganese, essential for INS-2 D Pinitol + Baeknyoncho 600mg + 1g / day Antidiabetic agent E Pinitol + maltodextrin 600 mg + 7.5 g / day Buoyant

Example  2: Selection and management of the subject

   (1) Target selection range

The experimental study subjects of the present invention selected people belonging to similar environments. As in many previous studies, we planned to avoid the approach of patients who visited the hospital and to see the effects of only the combination of pinitol and pinitol. In other words, the study of selecting the subjects with the same occupation contributed to the efficiency of the research because of the regular shift time and the ease of meeting. The subjects who have the same occupation selected by the present invention are taxi drivers. When selecting a research subject, they are requested from a taxi company and a major city in a metropolitan city to check for a simple postprandial blood glucose (2 hours after dinner) Tolerance) (about 180 mg / dL of postprandial glucose) were selected for the first time. In addition, we refer to the existing health checkup table of the parties during the first selection.

   (2) Subject excluded condition

Among the 1,000 candidates for the first selection, subjects who had the following conditions were excluded through the second health examination: (i) health checkups, (ii) alcoholism, mental retardation (including interviews), (iii) (V) kidney disease (serum creatinine> 20 mg / dL), (vi) liver disease, (3) liver disease, (AST and ALT twice the normal value), (ⅶ) cardiovascular disease, gastrointestinal disease, malignant tumor. We selected 350 secondary candidates out of a total of 1,000 who had been selected for the first time.

   (3) Blood measurement index of the subject

The measurement items of the subjects were as follows.

(I) Blood sugar check: Each subject was provided with a blood glucose check and strip for each individual. After the start of the first and second studies, the fasting blood glucose was checked every day for one week and the post-meal blood glucose was checked 2 hours after dinner. Blood glucose was checked in the same manner at intervals.

(Ii) Blood collection: Blood samples were taken before dosing, starting from the study. Blood samples were collected on the third day after the dosing, one week after the sampling, and then every week for one month. Then, a total of 4 blood samples were collected at intervals of 2 weeks, and a total of 13 blood samples were collected for 3 months. Insulin, blood sugar, hemoglobin, glycated hemoglobin, triglyceride, and cholesterol were analyzed for blood samples.

Example 3: Measurement of blood index before administration of a subject to be administered

Table 2 shows the results of measuring the blood indicators of the subjects selected as subjects of the present invention.

Item Pinitol combination preparation group
(80 in the first, 200 in the second: 280 in total) Placebo group
(Control group: 20 persons, 50 persons: total 70 persons) age 45.3 ± 5.1 6.5 ± 3.4 gender Male Male BMI (body mass index) 25.30 ± 5.74 26.30 + - 4.71 Blood pressure (systolic) 127.67 ± 15.74 128.65 + - 12.04 Blood pressure (diastolic) 76.67 + - 11.51 76.07 ± 13.32 Glycosylated hemoglobin (HbAlc,%) 9.45 + 1.51 7.45 1.51 Triglyceride 297.67 ± 11.72 197.67 ± 12.34 Total cholesterol 245.37 ± 12.02 155.63 + - 13.24 HDL-cholesterol 37.67 ± 14.47 30.67 ± 11.73 LDL-cholesterol 107.63 + - 11.04 101.67 + - 10.74 Hemoglobin (g / dL) 13.45 1.51 13.65 ± 2.53 AST (U / L) 23.04 + - 1.33 24.05 ± 1.42 ALT (U / L) 22.02 + - 1.82 24.07 ± 1.53 Creatinine (mg / dL) 0.91 + - 0.12 0.88 0.15 Blood sugar (2 hours after meals) 180 ± 11.34 120 ± 15.37 Insulin ( u U) (2 hours after meals) 12 ± 1.54 30 ± 2.54

Before administering the combination preparation of the present invention to the subjects, the five main indicators to be checked in the present study were obtained from the blood. In the five main indicators, glycated hemoglobin, triglycerides, cholesterol, and blood glucose were higher than the control (normal, healthy group) and insulin levels were higher in the control group than in the control group. Subsequently, a total of 350 subjects (including 50 control subjects) were administered the combination of the pinitol formulation described in Table 1 above. In the first administration trial, 10 patients were assigned to each combination and 20 patients in the placebo group (control group: 10 patients, placebo group: 10 patients). A total of 4 blood samples were collected after the administration of the combined preparation and the life management records were presented. Table 3 and Figure 8 show the results of the analysis during the first administration period. Table 4 also shows the life management records during the study period.

Item Pinitol combination preparation group Placebo group (control) Transfer to before Preparation and control group A Pinitol combination preparation Placebo control General control group Type of preparation B C D E Glycosylated hemoglobin (HbAlc,%) 7.45 1.51 7.45 1.51 Triglyceride (mg / dL) 197.6 ± 12.34 197.6 ± 12.34 Total Cholesterol (mg / dL) 155.6 ± 13.24 155.6 ± 13.24 HDL-cholesterol 30.67 ± 11.73 30.67 ± 11.73 LDL-cholesterol 101.6 ± 10.74 101.6 ± 10.74 Insulin ( u U) 30 ± 2.54 30 ± 2.54 Blood sugar (mg / dL) 120 ± 15.37 120 ± 15.37

As shown in Table 3 above, when the combination of pinitol sole A and pinitol is compared, the difference of D, which is a mixture of pinitol and white perilla, is significantly different. Next, B was an effective formulation. Based on these results, we tried to analyze the second dose using the above four agents. On the other hand, the criteria for selection of the drug to be used in the second administration experiment was the first to be applied so that the timing of the effect is markedly faster than that of A, and therefore, the blood sugar level and the glycated hemoglobin were lowered.

Item Writer :
Record Date (2011 年 1 日 - 2011 年 月 日) month anger Number neck gold Sat Work Drinking status, alcohol content Whether tobacco, quantity Whether or not eating, visual record Kind of meal (breakfast) Kind of meal (lunch) Types of meals (evening) Exercise, time of exercise Blood glucose check, numerical record Send blood sugar figure Whether or not to take medicine, Total sleep time Bedtime - Warm-up time Others (eg irregular life)

Example  4: Before administration  Blood indicator measurement

The analysis of the four kinds of the combination of pinitol selected through the first administration experiment was carried out on 250 persons of the second administration experiment. In the second administration experiment, the blood glucose check and intensive lifestyle management were performed twice a day under more stringent conditions than the first administration experiment. A total of 200 experimental groups were assigned to each compound of pinitol. The control group consisted of 50 patients in the placebo group.

Table 5 and FIG. 9 show changes in blood glucose, insulin, triglyceride, and cholesterol at each blood sampling time. Table 6 and Fig. 10 show the results of comparing the mean of fasting blood glucose and postprandial blood glucose, measured regularly during the second administration period, before and after the administration.

Item Pinitol combination preparation group Placebo group
(Control group) Transfer to before Preparation and control group A Pinitol combination preparation Type of preparation B D Glycosylated hemoglobin (HbAlc,%) 7.45 1.51 7.45 1.51 Triglyceride (mg / dL) 197.6 ± 12.34 197.6 ± 12.34 Total Cholesterol (mg / dL) 155.6 ± 13.24 155.6 ± 13.24 HDL-cholesterol 30.67 ± 11.73 30.67 ± 11.73 LDL-cholesterol 101.6 ± 10.74 101.6 ± 10.74 Insulin ( u U) 30 ± 2.54 30 ± 2.54 Blood sugar (mg / dL) 120 ± 15.37 120 ± 15.37

According to the results shown in Table 5, as shown in Table 3, the combination formulations B and D selected against the pinitol alone group A showed a hypoglycemic effect. In addition, other major indicators also showed significant changes.

Item Pinitol combination preparation group Placebo group
(Control group) Before dosing Preparation and control group Blood glucose level
division A Pinitol combination preparation Placebo control Type of preparation B D Before dosing Blood sugar (mg / dL) - 180 ± 11.34 180 ± 11.34 180 ± 11.34 120 ± 15.37 120 ± 15.37 After the injection Fasting blood sugar
(mg / dL) Highest figure Lowest figure Variation Postprandial glucose
(mg / dL) Highest figure Lowest figure Variation

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the same is by way of illustration and example only and is not to be construed as limiting the scope of the present invention. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

Claims (3)

(i) as the first component: pinitol; And (ii) as a second component, a myoinositol or perennial extract.
The combination kit according to claim 1, wherein the combination of the first component and the second component has a synergistic effect of treating or preventing diabetes.
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