METHYL SULFONYL METHANE-CONTAINING COMPOSITION FOR PREVENTING OR ALLEVIATING OBESITY, FATTY LIVER, AND DIABETES
20210267912 · 2021-09-02
Inventors
Cpc classification
A61K36/899
HUMAN NECESSITIES
A23L33/40
HUMAN NECESSITIES
A61K31/519
HUMAN NECESSITIES
A23L33/105
HUMAN NECESSITIES
A23V2002/00
HUMAN NECESSITIES
A23V2200/328
HUMAN NECESSITIES
A23L33/125
HUMAN NECESSITIES
A61K36/899
HUMAN NECESSITIES
A61K2300/00
HUMAN NECESSITIES
A61K2300/00
HUMAN NECESSITIES
A61K33/06
HUMAN NECESSITIES
A61K31/702
HUMAN NECESSITIES
A61P1/16
HUMAN NECESSITIES
International classification
A23L33/00
HUMAN NECESSITIES
A23L33/105
HUMAN NECESSITIES
A23L33/125
HUMAN NECESSITIES
A61K31/519
HUMAN NECESSITIES
A61K31/702
HUMAN NECESSITIES
A61K33/06
HUMAN NECESSITIES
A61K36/899
HUMAN NECESSITIES
A61P1/16
HUMAN NECESSITIES
Abstract
The present invention relates to a methyl-sulfonyl methane containing composition for preventing or alleviating obesity, fatty liver and diabetes. An MSM (methyl sulfonyl methane: dimethyl sulfone)-containing composition according to the present invention, which contains 75 to 85 wt. % of MSM, 0.5 to 2 wt. % of vitamin B6 hydrochloride, 0.01 to 1 wt. % of folic acid, 2 to 8 wt. % of galacto-oligosaccharide, 10 to 18 wt. % of rice-fermented magnesium, and 0.5 to 3 wt. % of vitamin C, not only can prevent and treat obesity by reducing the size of fat cells and inhibiting differentiation of mature fat cells, but also lowers triglyceride and the total cholesterol concentration in the liver, thus having a fatty liver preventing effect, and also reduces the concentration of insulin-like growth factor, thus also being effective for diabetes. Therefore, the MSM-containing composition is expected to be useful as a pharmaceutical composition and food composition for preventing and alleviating obesity, fatty liver and diabetes.
Claims
1. A pharmaceutical composition for preventing or treating obesity, comprising: 75 to 85% by weight (“wt. %”) of methylsulfonylmethane (MSM: dimethyl sulfone); 0.5 to 2 wt. % of vitamin B6 hydrochloride; 0.01 to 1 wt. % of folic acid; 2 to 8 wt. % of galactooligosaccharide; 10 to 18 wt. % of rice fermented magnesium; and 0.5 to 3 wt. % of vitamin C.
2. A pharmaceutical composition for preventing or treating fatty liver, comprising: 75 to 85 wt. % of methylsulfonylmethane (MSM: dimethyl sulfone); 0.5 to 2 wt. % of vitamin B6 hydrochloride; 0.01 to 1 wt. % of folic acid; 2 to 8 wt. % of galactooligosaccharide; 10 to 18 wt. % of rice fermented magnesium; and 0.5 to 3 wt. % of vitamin C.
3. A pharmaceutical composition for preventing or treating diabetes, comprising: 75 to 85 wt. % of methylsulfonylmethane (MSM: dimethyl sulfone); 0.5 to 2 wt. % of vitamin B6 hydrochloride; 0.01 to 1 wt. % of folic acid; 2 to 8 wt. % of galactooligosaccharide; 10 to 18 wt. % of rice fermented magnesium; and 0.5 to 3 wt. % of vitamin C.
4. A food composition for preventing or alleviating obesity, comprising: 75 to 85 wt. % of methylsulfonylmethane (MSM: dimethyl sulfone); 0.5 to 2 wt. % of vitamin B6 hydrochloride; 0.01 to 1 wt. % of folic acid; 2 to 8 wt. % of galactooligosaccharide; 10 to 18 wt. % of rice fermented magnesium; and 0.5 to 3 wt. % of vitamin C.
5. A food composition for preventing or improving fatty liver, comprising: 75 to 85 wt. % of methylsulfonylmethane (MSM: dimethyl sulfone); 0.5 to 2 wt. % of vitamin B6 hydrochloride; 0.01 to 1 wt. % of folic acid; 2 to 8 wt. % of galactooligosaccharide; 10 to 18 wt. % of rice fermented magnesium; and 0.5 to 3 wt. % of vitamin C.
6. A food composition for preventing or alleviating diabetes, comprising: 75 to 85 wt. % of methylsulfonylmethane (MSM: dimethyl sulfone); 0.5 to 2 wt. % of vitamin B6 hydrochloride; 0.01 to 1 wt. % of folic acid; 2 to 8 wt. % of galactooligosaccharide; 10 to 18 wt. % of rice fermented magnesium; and 0.5 to 3 wt. % of vitamin C.
Description
BRIEF DESCRIPTION OF DRAWINGS
[0037] The following drawings attached to this specification are provided to illustrate exemplary embodiments of the present invention, and will serve to further illustrate the technical spirit of the present invention together with the above-described contents of the present invention. Therefore, it should not be construed that the present invention is limited to the matters described in the drawings.
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DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS OF INVENTION
[0048] Hereinafter, preferred examples and the like are provided to facilitate understanding of the present invention. However, the following examples are provided only to more easily illustrate the present invention, and the contents of the present invention are not limited by the same.
[Example 1] Preparation of Composition Containing methylsulfonylmethane
[0049] A composition containing methylsulfonylmethane (“MSM-containing composition”) having a constitutional composition as shown in Table 1 below was prepared.
TABLE-US-00001 TABLE 1 No. Component Content (%) 1 MSM 80.000 2 Vit. B6 1.100 3 Folic Acid 0.050 4 Galactooligosaccharide 4.000 5 Rice fermented magnesium 13.399 6 Vit. C 1.450 7 Vit. B12 mixed powder 0.001 Total 100
<Experimental Example 1> Inhibitory Effects on Body Weight Gain in High Fat Diet Obese Mouse Model by the Composition According to the Present Invention
[0050] As experimental animals, C57BL/6 series 8-week-old male mice were adapted with solid feed for 1 week, and were divided into 3 groups with an average body weight of 25 g according to randomized block design and bred for 8 weeks.
[0051] The experimental groups were divided into: a normal diet group (NCD); a high fat diet group (HFD); a group having a high fat diet and the MSM-containing composition obtained in Example 1 (HFD+MSM (0.0088%)); a group having a high fat diet and the MSM-containing composition obtained in Example 1 (HFD+MSM (0.017%)), followed by implementing experiments. The normal diet group was fed a general diet wherein fat was 10% of total calories, while the high fat diet group was fed a diet wherein fat was 60% of total calories. Further, with regard to the groups having ingested the high fat diets together with the MSM-containing compositions, the diets fed to these groups were prepared by adding 0.0088% and 0.017% MSM-containing compositions, respectively, to the high fat diets. During the breeding period, water and feed were freely afforded. A temperature in the breeding space was maintained at 22±1° C. while illumination was controlled on 12-hour cycle (08:00 to 20:00). All animal experiments were performed while complying with Animal Experimentation Ethic Code under approval of the Science and Technology Institutional Animal Care and Use Committee.
[0052] The results obtained in the experiments were expressed as the average±standard error for each experimental group, and statistical analysis of the mean difference between the two groups was analyzed by Student's t test, followed by verifying significance of the result at P<0.05 level.
[0053] Dietary intake and body weight of the test animals were measured once a week. The body weight gain rate of each experimental group was measured at a predetermined time and a predetermined interval of 1 week during the experimental period, and the food efficiency ratio (FER) was calculated by dividing total body weight gain by dietary intake during the experimental period, which was defined as a duration from the feeding date of the experiment diet to the sacrifice date.
[0054] Effects of the MSM-containing composition according to the present invention on dietary intake and body weight are shown in Table 2 for individual groups.
TABLE-US-00002 TABLE 2 Food Total body Total efficiency Test weight gain dietary ratio group (g) intake (g) (FER) (%) p-value NCD 5.3 42.13 12.5 ± 1.7 — HFD 21.3 31.30 68.1 ± 3.9 0.000 HFD + 11.7 31.32 37.9 ± 7.8 0.031 MSM (0.008%) HFD + 11.6 31.00 38.9 ± 4.0 0.003 MSM (0.018%)
[0055] As shown in Table 2, FER of the high fat diet group was about 5.4 times higher than the normal diet group, but it was found that FER of the high fat diet+MSM-containing composition intake group was decreased by about 1.8 times, as compared to the normal diet group. On the other hand, as compared to the normal diet group, the body weight was rapidly increased in the high fat diet group while the body weight gain in the high fat diet+MSM-containing composition intake group was significantly reduced. Therefore, it could be confirmed that intake of the MSM-containing composition significantly inhibits body weight gain caused by the high fat diet.
<Experimental Example 2-1> Fat Accumulation Inhibitory Effects of MSM-Containing Composition in High Fat Diet Obese Mouse Model
[0056] Breeding, diet and statistical treatment of the experimental animals were performed in the same manner as in Experimental Example 1. In order to confirm fat accumulation inhibitory effects of the MSM-containing composition according to the present invention, the fat and liver tissues of the test animals were separated and weighed.
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[0059] As shown in
<Experimental Example 2-2> Effects of Adipose Cell Size Reduction and Fatty Liver Improvement in High Fat Diet Obese Mouse Model
[0060] Breeding, diet and statistical treatment of experimental animals were performed in the same manner as in Experimental Example 1. For morphological observation of the experimental animals, liver tissues were extracted after experiment, and then fixed in a 4% paraformaldehyde solution after water removal. The fixed tissues were washed with running water, followed by dehydration in ethanol in sequential order of increased concentration. Then, the treated tissues were subjected to infiltration and embedding in paraffin, followed by preparing 4 μm tissue sections, staining the same with hematoxylin and eosin. Thereafter, the stained tissues were observed under an optical microscope.
[0061] As compared to the normal diet group, the size of adipose cells in the high fat diet group was considerably increased, whereas the high fat diet and MSM-containing composition intake group showed significantly reduced size of adipose cells. Therefore, it could be confirmed that the composition of the present invention is useful for treatment and prevention of obesity caused by high fat diet.
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<Experimental Example 3> Mature Adipocyte Differentiation Inhibitory Effects in High Fat Diet Obese Mouse Model
[0064] (1) 3T3-L1 Cell Culture and Differentiation
[0065] Mouse-derived 3T3-L1 cells were obtained from the American Type Culture Collection (ATCC, CL-173, Manassas, Va., USA) and used. After seeding 3T3-L1 pre-adipocytes at 1×10.sup.6 cells/well in 1000, 24-well and 96-well plates, respectively, depending upon purposes of the experiment, the cells were incubated in a high concentration of glucose DMEM (89%) containing BS(10%) and P/S(1%) to reach 100% confluence. 2 days later, the pre-adipocytes were subjected to induction of differentiation using an adipocyte differentiation-inducing substance (1 μg/mL insulin, 1 μM DEX, 0.5 mM IBMX) as well as DMEM containing FBS (10%) and P/S (10%). During adipocyte differentiation (day 0), samples were treated with DMEM at 25, 50 and 100 μg/mL, while a positive control was treated with 5 mM of NAC as an antioxidant, and then used for comparison.
[0066] In order to determine 3T3-L1 cell differentiation inhibitory efficacy, an amount of triglycerides generated in 3T3-L1 adipocytes was measured by Oil Red 0 staining to stain only triglycerides in red. A result of the measurement is shown in
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<Experimental Example 4> Blood Lipid Improvement Effects in High Fat Diet Obese Mouse Model
[0068] Breeding, diet and statistical treatment of the experimental animals were performed in the same manner as in Experimental Example 1. In order to confirm effects of improving blood lipids by the MSM-containing composition of the present invention, all animals were subjected to fasting for at least 12 hours after the end of experiment, followed by sacrificing and collecting blood. The collected blood was left at room temperature for 1 hour and then centrifuged at 3000 rpm to obtain serum, which in turn was analyzed using an automatic biochemical analyzer (BS-380, Mindray) to assess intrahepatic triglycerides and total cholesterol.
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[0071] As shown in the figures, it could be confirmed that the triglyceride and total cholesterol contents have returned to substantially normal levels as a result of administration of the MSM-containing composition for 3 weeks to the obese mice.
<Experimental Example 5> Measurement of In Vitro Lipolysis by MSM-Containing Composition
[0072] Lipolysis experiments were implemented using normal milk coffee and Korean chicken soup (“Samgyetang”). The milk coffee was added to the MSM-containing composition of the present invention and then dissolved, followed by visual observation of lipolysis.
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[0075] As shown in the figures, it could be visually confirmed that fats were decomposed in the milk coffee and samgyetang to which the MSM-containing composition according to present invention was added, respectively.
<Experimental Example 6> Determination of Insulin-Like Growth Factor Secretion Ability of MSM-Containing Composition
[0076] In the present experimental example, insulin-like growth factor (IGF-1) secretion ability of the MSM-containing composition was tested.
[0077] Analyzers used herein were ELISA readers (LAB SYSTEM, USA) and ELISA kits (rat IGF-1, catalog #DSL 10-2900, Diagnostic Systems Laboratories, USA), while a data analysis and statistical system used herein was Prism (ver. 2.01, GraphPad Software Inc., USA).
[0078] Sprague Dawley rats were used as test animals. The test animals were 3 weeks of age for the long-term administration test and 9 weeks of age for the IGF-1 evaluation test. The test animals were male and 30 animals were assigned for each test (10 for controls, 10 for examples, 10 for comparative examples). Breeding conditions of the test animals were set to: temperature 22±3 (19 to 25) ° C.; humidity 30 to 70%; photoperiod 12 hours (light cycle: 08:00 to 20:00).
[0079] For IGF-1 evaluation test, all animals were used after fasting for 24 hours in order to control a basic amount of growth hormone in the blood or for concurrency. For the test group, a daily dose (1,500 mg/day based on a 60 kg human) was orally administered. The control group was supplied with the same volume of drinking water as the test group. Tail blood was collected at 0 hours and, after oral administration, 0.1 ml or less of blood was collected at 2 hour intervals up to 10 hours, followed by serum separation to prepare a measurement sample. IGF-I measurement was implemented using a kit product by means of ELISA.
[0080] Since growth hormone secretion mostly occurs by instantaneous release called pulse mode, it is very difficult to measure a change in growth hormone secretion in response to physiological stimulation. Indeed, although the hormone flows through the bloodstream for only a few minutes, this is enough for the hormone to enter the liver and stimulate the same so as to be converted into growth factors in the liver. IGF-1 secretion is used to measure an amount of growth hormone secretion, wherein IGF-1 has more diverse activities than the growth hormone itself and directly acts on most biological activities. Therefore, in the present test, an amount of blood IGF-1 secretion as a secondary signal of growth hormone was measured, and IGF-1 remained stable in blood after stimulation and substantially showed effects of growth hormone.
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[0082] As shown in the figure, the amount of IGF-1 secretion in the control group was continuously decreased, whereas the MSM-containing composition significantly increased the amount of IGF-1 secretion. Therefore, it could be confirmed that the MSM-containing composition according to the present invention exhibits excellent effects of promoting secretion of IGF-1, which is an insulin-like growth factor