WO2011074765A2 - Composition including fermented material for oriental medicine as an active ingredient for preventing and treating obesity or hyperlipidemia - Google Patents
Composition including fermented material for oriental medicine as an active ingredient for preventing and treating obesity or hyperlipidemia Download PDFInfo
- Publication number
- WO2011074765A2 WO2011074765A2 PCT/KR2010/006079 KR2010006079W WO2011074765A2 WO 2011074765 A2 WO2011074765 A2 WO 2011074765A2 KR 2010006079 W KR2010006079 W KR 2010006079W WO 2011074765 A2 WO2011074765 A2 WO 2011074765A2
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- Prior art keywords
- fermented
- fermentation
- obesity
- hyperlipidemia
- extract
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Images
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/38—Other non-alcoholic beverages
- A23L2/382—Other non-alcoholic beverages fermented
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Definitions
- Obesity is a metabolic disorder caused by an imbalance between calorie intake and consumption and is defined as an increased state of adipose tissue (Kopelman PG. And Stock MJ.). Obesity affects all age groups, especially in older adults. In addition, the fact that obesity can cause serious diseases such as hyperlipidemia, diabetes, cholelithiasis, and cardiovascular diseases such as arteriosclerosis and hypertension, is considered as a disease beyond obesity and metabolic disorders or risk factors of the disease. Family Medicine, 1994, 15 (7), 401-410; Journal of the Korean Academy of Family Medicine, 1992, 13 (4), 344], it is known that the risk of adult disease due to obesity is three to six times higher than that of normal people.
- the main cause of obesity is the inability to control food intake by itself and due to excessive food supply, the amount of energy consumed is continuously excessive compared to the energy consumed.
- Therapeutic drugs used in pharmacotherapy include digestive absorption inhibitors, anti-absorption inhibitors, or metabolic accelerators, but these drugs can put a burden on the human body and cause digestive problems.
- a fat absorption blocker has the effect of blocking the absorption of fat in the digestive tract, but there are various side effects such as diarrhea in the digestive system, so only limited use is possible, and weight loss agents due to psychotropic drugs Heart and circulatory side effects and side effects when taken at the same time with other drugs can not be used without a doctor's prescription.
- the present inventors have tried to find a drug that shows the therapeutic effect of obesity and hyperlipidemia from various herbal medicines derived from plants, which have been ingested for a long time and are guaranteed stability, and improve the absorption rate of such drugs in vivo and anti-obesity and anti-hyperlipidemia of the drug. While trying to find a method for maximizing efficacy, the present invention was completed by discovering drugs that exhibit anti-obesity and anti-hyperlipidemic effects and finding a method that can ensure the absorption and stability of such drugs in vivo.
- the present invention relates to a composition for the prevention and treatment of obesity or hyperlipidemia, including the herbal medicine fermented product or extract of the fermented product as an active ingredient.
- the present invention relates to a health food for the prevention and treatment of obesity or hyperlipidemia, and a pharmaceutical composition for the prevention and treatment of obesity or hyperlipidemia, including the herbal medicine fermented product or extract of the fermented product as an active ingredient.
- the heart of the mulberry is mulberry ripe mulberry fruit
- Audi has the effect of nourishing tonic that the hair is black when eaten a lot and gradually turns red from blue to purple to black.
- It is known as a medicine that does not grow old because it makes blood very clean.It helps the liver and kidneys to treat bleeding, which helps to treat the small thirst (diabetes) caused by depletion of the essence, dry mouth, dry tongue and lack of adultery. It is effective for dizziness and insomnia. It is also known as a medicine that is effective in constipation and softens the intestines, which leads to lack of blood.
- the medicine consisting of phalanges, creation, heartache will be named Samjeonghwan.
- the present invention relates to a composition for the prevention and treatment of obesity or hyperlipidemia comprising the phalanx, phalanx, extract, fermented extract of fermented products, or as an active ingredient, the weight of the creation, phalanges, and loser is specifically limited However, preferably when the weight of the creation is set to 10, the weight of the phalanges may include 8 to 12, the weight of the heartache 18 to 22 may include the medicine.
- the present invention converts the drug into a low-molecular substance that is easily absorbed by human cells through a fermentation process or by additionally generating a useful material for the human body by decomposing organic substances using enzymes that microorganisms have during fermentation. Not only did it significantly increase obesity efficacy, it could also perform intestinal immunity and detoxification functions.
- the strain used to prepare the fermentation is isolated from the strains occupying the dominant species in the fermentation, Bifidobacterium longum (Bifidobacterium longum) and Bifidobacterium breve (Bifidobacterium breve) It may be a microorganism selected from the group consisting of.
- the fermented product may be used as it is, and the fermented product may be extracted to provide a composition for the prevention and treatment of obesity or hyperlipidemia containing the extract of the fermented product as an active ingredient.
- a mixed solvent having a mixing ratio, preferably methanol, may be used, and the solvent may be 5 to 100%, preferably 80 to 100%.
- the extraction time may be hot water extraction, cold needle extraction, reflux cooling extraction or ultrasonic extraction, preferably hot water extraction for 1 hour to 48 hours, preferably 12 hours to 36 hours, and the hot water extraction temperature is not particularly limited. Preferably it can be extracted at 40 to 80 °C, more preferably 50 to 70 °C, the extraction may be carried out repeatedly. In the extraction time and temperature, the extraction time can be reduced by increasing the extraction temperature, but excessively high temperature can destroy useful bacteria in fermented medicinal herbs to reduce the absorption rate of the medicament, Substance generation and intestinal immunity and toxin removal may be reduced. If the extraction temperature is too low, the extraction time increases and there is a problem that the active ingredient of the drug may not be completely extracted. The extract can be cooled, filtered and concentrated under reduced pressure to obtain an extract usable in the present invention.
- the present invention provides a pharmaceutical composition for the prevention and treatment of obesity or hyperlipidemia, including the phalanx, the production, the fermented product including the loser or extract of the fermented product as an active ingredient.
- Carriers, excipients and diluents which may be included in the pharmaceutical composition comprising fermented products or extracts of fermented products include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin , Calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
- Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient, for example, starch, calcium carbonate, in the fermentation or extract of the fermentation product. Prepared by mixing sucrose or lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used.
- Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin.
- Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories.
- the non-aqueous solvent and suspending agent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used.
- As the base of the suppository witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
- the preferred dosage of the fermentation or extract of the fermentation of the present invention depends on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art.
- the fermentation product or the extract of the fermentation product of the present invention is preferably administered at 0.0001 to 100 mg / kg, preferably 0.001 to 100 mg / kg, but the dosage is changed depending on the condition of the patient. You may. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect.
- Fermentation products or extracts of the fermentation products of the present invention can be used in a variety of health foods and beverages for the prevention and treatment of obesity or hyperlipidemia.
- Examples of the food to which the present fermented product or extract of the fermented product can be added include various foods, beverages, gums, teas, vitamin complexes, and health foods.
- Fermented product or extract of the fermented product of the present invention has little toxicity and side effects, so can be used with confidence even for long-term use for the purpose of prevention. Fermentation products or extracts of the fermentation products of the present invention may be added to food or beverage.
- the amount of the fermentation product or the extract of the fermentation product in the food or beverage may be added to 0.01 to 50% by weight of the total food weight, the health beverage is 0.02 to 30 g, preferably 0.3 to 10 g based on 100 ml Can be added.
- the health beverage of the present invention is not particularly limited to other ingredients except for containing the fermented product or extract of the fermented product as essential ingredients in the indicated ratios, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks.
- natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol.
- the fermented products or extracts of the fermented products of the present invention include various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors such as flavoring agents, colorants and neutralizing agents (cheese, chocolate, etc.), pectic acid and its Salts, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks and the like.
- the fermentation products or extracts of the fermentation products of the present invention may contain the flesh for the production of natural fruit juice and fruit juice beverage and vegetable beverage. These components can be used independently or in combination. The proportion of such additives is not so critical, but is generally selected from the range of 0 to about 20 parts by weight per 100 parts by weight of the fermentation product or extract of the fermentation product.
- the present invention provides a composition for the prevention and treatment of obesity or hyperlipidemia, containing the fermentation product of herbal medicine or extract of the fermentation product including phalanx, phalanx, heartache as an active ingredient.
- the composition of the present invention will not only be excellent in the effects of anti-obesity and anti-hyperlipidemia, but also can be used as a medicine and health food using it because of its excellent safety in vivo absorption and no toxicity or side effects.
- Figure 2 is a graph of quantitative evaluation of the results of observing the expression of PPAR-r and CEBPa, adifferentiation-related genes in 3T3-L1 cells by real time PCR, and the UCP-2 protein associated with heat generation. The most pronounced results were obtained at high doses of FH2.
- Figure 4a shows the change in body weight of the normal group fed normal feed (normal), obesity-induced group fed high fat feed (HFD) and obese + samjeonghwan group fed high fat feed and fermented samjunghwan (HFD + SJH) .
- Figure 4b shows the heart, spleen and kidney of the normal group fed normal feed (normal), the obesity-induced group fed high fat feed (HFD) and the obesity + samjunghwan group (HFD + SJH) fed high fat feed and fermented samjunghwan , Liver, epididymal fat, and abdominal visceral fat were measured.
- normal normal
- HFD obesity-induced group fed high fat feed
- HFD + SJH obesity + samjunghwan group
- Figure 4c shows normal triglycerides in the normal group fed normal feed, obesity-induced group fed high fat feed (HFD), and obese + samjeonghwan group fed high fermented samjunghwan (HFD + SJH). It shows the difference between high density lipoprotein and low density lipoprotein in blood.
- HFD obesity-induced group fed high fat feed
- HFD + SJH obese + samjeonghwan group fed high fermented samjunghwan
- Figure 5 shows a microbial detection photograph for each medium.
- Figure 6 shows a microscopic microscope image of each medium.
- Figure 8 shows the pH change of the fermentation strains during the total fermentation period of three fermentation of three fermentation of three fermentation of three fermentation of three fermentation of three fermentation, three fermentation of Lactobacillus plantarum P23, three fermentation of Yeast DSII, three fermentation of Lactobacillus plantarum P23 and Yeast DSII.
- FIG. 11 shows chromatograms (UV 254 nm analysis results) before and after fermentation of Samjunghwan medicinal products by lactic acid bacteria ( B. longum, E. faecium, P. pentosaceus) . It is not yet known which substances have the effect of inhibiting fat synthesis, but at least before and after fermentation, there are many active substance changes .
- Figure 14 shows the ability to inhibit the differentiation of fat cells of Samjunghwan fermented with five lactic acid strains.
- composition of the present invention that is not fermented was produced by grinding 600 g of each of the phalanges, phalanges, and made into juice by squeezing the freshener 1200 g into raw materials.
- the fermented composition of the present invention is made by grinding 600 g of each of the phalanges, phalanges, and powder, and squeezed 1200 g of raw heartwood into juice. After fermentation in 35 days was prepared in a ring.
- the pre-adipocyte 3T3 L-1 cells used in the experiment were purchased from the American Type Culture Collection (Rockville, MD, USA). Cells were cultured in DMEM (Invitrogen, USA) medium containing 10% Fetal Bovine Serum (FBS; Invitrogen, USA) in a 37 ° C., 5% CO 2 incubator. To prevent contamination, 100 units / ml penicillin and 100 ug / ml streptomycin (Gibco / BRL, USA) were added as antibiotics. Subsequent passages were treated with Trypsin-EDTA (Gibco / BRL, USA). The medium was changed every 2-3 days.
- adipocytes To differentiate into adipocytes, transfer to a 6-well plate (Corning, USA) in the number of 1 ⁇ 10 5 / well and exchange with a primary differentiation medium containing 10 ⁇ g / ml Insulin, 0.25 ⁇ M Dexamethasone, 0.5 mM IBMX Induce differentiation into adipocytes for 6 days in medium containing 5 ⁇ g / ml Insulin, a differentiation medium. The medium was replaced with fresh medium every two days. The concentration of the cells was treated by diluting 500 and 1000 times the fermentation and fermented Samjunghwan, respectively, to the cells.
- PPAR-gamma, SREBP-1c and TNF-alpha genes involved in adipocyte differentiation were observed using real time PCR. After 24 hours, two concentrations of Samjunghwan and fermented Samjunghwan concentrates were differentiated into differentiated adipocytes. RNA was extracted from the cells using Trisol (Invitrogen, USA) to synthesize cDNA. PCR (Light cycler 480, Boeringer Manheim, Germany) was performed and the expression level of each gene was calculated with beta-actin.
- White rats were divided into 6 rats in each group (normal group, obesity-inducing group, obesity + samjung-hwan group).
- Total cholesterol in blood was measured using A-CHO T-CHO kit. After mixing 3 ml of enzyme reagent in 20 ⁇ l of Serum, the solution was incubated at 37 ° C. for 5 minutes and absorbed at 500 nm within 60 minutes.
- Blood triglycerides were measured using Asan Pharmaceutical's Triglyceride Test Kit (Cleantech TG-S). After mixing 3 ml of enzyme reagent in 20 ⁇ l of Serum, the solution was incubated at 37 ° C. for 10 minutes, and the absorbance was measured at 550 nm within 60 minutes.
- HDL-Cholesterol High Density Lipiprotein
- Blood HDL was measured using Aesque Pharmaceutical's Ezediel Colletase Test Solution (HDL-CHO) kit. After mixing 3 ml of enzyme reagent in 200 ⁇ l of Serum, the solution was incubated at 37 ° C. for 5 minutes, and the absorbance was measured at 500 nm within 60 minutes.
- HDL-CHO Aesque Pharmaceutical's Ezediel Colletase Test Solution
- LDL-Cholesterol Low Density Lipiprotein
- Microorganism analysis other than lactic acid bacteria of the present invention was carried out in accordance with the 2008 Food Code, Health Functional Food Code, Korea Pharmacopoeia, was prepared by diluting 1g of fermented herbal medicine Samjunghwan powder in 9ml of sterilized anaerobic water.
- the contamination detection medium was 37 ° C. for 48 hours using Plate Count Agar (PCA), Trypic Soy Agar (TSA), Nutrient Agat (NA), Blood Plate Agar (BAP), SBM, and KF. Cultures (42 ° C for SBM) and fungi were cultured in aerobic culture at 25 ° C for 5 days using DRBC Agar and Potato Dextrose Agar (PDA) as contamination detection media.
- PCA Plate Count Agar
- TSA Trypic Soy Agar
- NA Nutrient Agat
- BAP Blood Plate Agar
- SBM Blood Plate Agar
- KF KF.
- Cultures (42 ° C for SBM) and fungi were cultured in aerobic culture at 25 ° C for 5 days using DRBC Agar and Potato Dextrose Agar (PDA) as contamination detection media.
- PDA Potato Dextrose Agar
- For detection of pathogens Oxford agar, MYP, Macconky agar, and MSA were used for the detection of path
- the number of bacteria was measured by comparing with the standard graph of each strain.
- the standard graph for each strain was cultured for each strain to measure the number of bacteria present in 1 mL, and DNA was extracted using the strain present in 1 mL. After dilution by dilution method, real-time PCR using SYBR Green I was performed, and a graph was used as data.
- 0.1g Samjunghwan powder was dissolved in Lysozyme, and DNA was extracted using a DNA preparation kit.
- Table 5 Table 6
- Table 7 shows the PCR conditions and primers for eight strains of Bifidobacterium longum, Bifidobacterim bifidum, Bifidobacterium breve, Lactobacillus acidophilus, Escherichia coli, Salmonella spp., Candida albicans, Bacteroides fragilis, Table 8 And Figure 7 shows the amount of each strain present in the Samjunghwan powder.
- Table 8 Amount of each strain present in Samjunghwan powder division Amount present in Samjunghwan Powder Bifidobacterium longum 2.10E + 04 Lactobacillus acidophilus 3.00E + 05 Bifidobacterium bifidum 4.00E + 04 Bifidobacterium breve 1.10E + 03 Escherichia coli 6.00E + 02 Salmonella spp. 1.30E + 02 Candida albicans 4.60E + 06 Bacteroides fragilis 5.00E + 01
- CP value was converted to the number of bacteria using the standard curve measured previously.
- the lactic acid bacteria fermented, fermented, fermented, fermented, fermented, fermented, fermented, fermented, fermented, fermented, fermented, fermented, fermented, fermented, fermented, fermented, fermented, fermented, fermented, fermented, Yeast fermentation was confirmed that the fermentation effect is superior to natural fermentation.
- the fermented Samjeong hwan, fermented Samjeong hwan, yeast fermented Samjeong hwan were not fermented because the fermented samjeong hwan was more effective than the fermented Samjeong hwan. It can be seen that the anti-obesity effect is superior to the ring.
- the fastest fermentation of the lactic acid bacterium fermented Samjung-hwan is performed smoothly within one week and almost all reducing sugars are consumed in the second week, and the fermented Samjeong-hwan and yeast fermented Samjeong-hwan are It showed a pattern of consuming sugar at about the same speed, and fermentation proceeded rapidly after 3 weeks of rapid consumption of sugar.
- the fermented Samjeong hwan, fermented Samjeong hwan, yeast fermented Samjeong hwan were not fermented because the fermented samjeong hwan was more effective than the fermented Samjeong hwan. It can be seen that the anti-obesity effect is superior to that, among which the lactic acid bacteria fermented Samjung-hwan shows a good fermentation effect within the shortest time, and thus the anti-obesity effect is also excellent.
- the strains used for fermentation are Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus plantarum P23, Enterococcus faecium, Pediococcus pentosaceus.
- L. plantarum P23 and P. pentosaceus are plant lactic acid bacteria isolated from Kimchi.
- Lactobacillus spawn was incubated at a concentration of about 10 7 cfu / ml (1%) and incubated at 37 ° C. for up to 61 hours.
- Some of the fermentation broth in the middle of fermentation and after fermentation were removed by lactic acid bacteria through centrifugation, and pH change was measured over time using supernatant. In addition, the supernatant before and after fermentation was analyzed for chromatogram change using
- Vitamin B6 0.5 mg
- composition ratio of the vitamin and mineral mixture is a composition suitable for a relatively healthy food in a preferred embodiment
- the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method.
- the granules may be prepared and used for preparing a health food composition according to a conventional method.
- the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilization and refrigerated Used to prepare the healthy beverage composition of the invention.
- composition containing the fermentation product including the creation of the present invention, phalanges, lettuce, as an active ingredient can be used as a pharmaceutical or health food for the prevention and treatment of obesity and hyperlipidemia.
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Abstract
The present invention relates to a composition including a fermented material for oriental medicine or an extract of the fermented material as an active ingredient for preventing and treating obesity or hyperlipidemia, and more particularly, to a composition including a fermented material for oriental medicine containing Atractylodes lancea, Lycium barbarum L., and Morus alba L., or an extract of the fermented material as an active ingredient for preventing and treating obesity and hyperlipidemia. According to the present invention, the fermented material for oriental medicine or the extract of the fermented material not only have excellent effects against obesity and hyperlipidemia, but also a good bio-absorbency and biocompatibility, so that they can be used as medical and health food products.
Description
본 발명은 한약재 발효물 또는 발효물의 추출물을 유효성분으로 포함하는 비만 또는 고지혈증의 예방 및 치료용 조성물에 관한 것이다.The present invention relates to a composition for the prevention and treatment of obesity or hyperlipidemia comprising the herbal medicine fermented product or extract of the fermented product as an active ingredient.
인류가 풍요로운 사회로 점점 발전해 감에 따라 비만이 심각한 질병 중의 하나로 등장하게 되었고, 이에 세계보건기구 (WHO)는 비만을 치료해야할 질병의 대상이라고 선언하였다 (Cummings DE and Schwartz MW.). 비만은 열량의 섭취와 소비의 불균형으로 발생되는 대사성 질환이며, 지방조직의 증가 상태로 정의된다 (Kopelman PG. and Stock MJ.). 비만은 모든 연령층에 걸쳐 영향을 주고 있으며, 특히 장년층의 발생빈도가 높다. 또한, 비만으로 인해 고지혈증, 당뇨, 담석증 등과 동맥경화, 고혈압과 같은 심혈관계 질환 등의 심각한 질환이 발생될 수 있다는 사실은 비만을 단순한 대사 장애나 질병의 위험인자를 넘어 하나의 질환으로 여겨지고 있으며 [가정의학지, 1994, 15(7), 401∼410; 대한가정의학회지, 1992, 13(4),344], 비만으로 인해 성인병에 걸릴 위험은 정상인보다 3∼6배 높다고 알려져 있다.As mankind has developed into an affluent society, obesity has emerged as one of the serious diseases, and the World Health Organization (WHO) has declared it the object of a disease to be treated (Cummings DE and Schwartz MW.). Obesity is a metabolic disorder caused by an imbalance between calorie intake and consumption and is defined as an increased state of adipose tissue (Kopelman PG. And Stock MJ.). Obesity affects all age groups, especially in older adults. In addition, the fact that obesity can cause serious diseases such as hyperlipidemia, diabetes, cholelithiasis, and cardiovascular diseases such as arteriosclerosis and hypertension, is considered as a disease beyond obesity and metabolic disorders or risk factors of the disease. Family Medicine, 1994, 15 (7), 401-410; Journal of the Korean Academy of Family Medicine, 1992, 13 (4), 344], it is known that the risk of adult disease due to obesity is three to six times higher than that of normal people.
비만의 주요한 원인은 음식섭취량을 자력으로 조절하지 못하고 과도한 음식공급으로 인해, 섭취 에너지가 소비 에너지에 비해 지속적으로 과도하게 되는 것으로 이를 막기 위한 노력이 그간 계속되었다. 일부 비만 환자들은 식이요법과 운동요법을 통해 섭취 에너지량을 조절하려고 하였으며, 그 외 행동요법, 정신요법, 약물요법, 또는 외과요법 등이 병행되고 있지만, 각각이 가지고 있는 심각한 부작용으로 인하여 그 사용이 제한적이었다.The main cause of obesity is the inability to control food intake by itself and due to excessive food supply, the amount of energy consumed is continuously excessive compared to the energy consumed. Some obese patients tried to control the amount of energy consumed through diet and exercise, and behavioral therapy, psychotherapy, drug therapy, or surgical therapy were combined. It was limited.
식이요법의 경우, 지방이나 당분이 적은 음식을 선별하여 섭취함으로 영양 성분의 부족으로 인해 장기간 수행 시 건강한 신체를 유지하기 힘들고 음식의 절식이나 조절에 따른 심리적 부담감이 커지며, 운동요법의 경우 소비 에너지의 증가뿐만 아니라, 안정 시 대사율의 개선, 인슐린 저항성의 시정 및 체지방의 감소 등의 효과가 있다고 되어 있으나, 1회에 20분간의 호기적 운동을 주 3회 이상 행하는 것이 필요하다. 그런데, 운동요법은 통상 필요로 하지 않는 노력이나 부담, 불쾌감, 인내력을 요구하는 경우가 있으며, 따라서 장기간 체중감소를 계속할 수 없는 예가 매우 많다. 또는 극도의 비만에 대한 긴급치료가 필요한 경우에는, 약물요법 또는 외과요법 등이 행해지고 있으나, 외과요법은 환자에게 주는 부담이 매우 크다. 약물요법에 사용되는 치료약으로서는 소화흡수 저해제, 비만축적 방지제, 또는 대사촉진제 등이 있으나, 이는 이러한 약물을 사용함으로 인체에 부담을 주어 소화 장애를 일으키기도 하고, 투여한 환자에게 단기간에 내성이 생길 수도 있기 때문에 장기간 연속하여 사용할 수 없다는 문제점 등이 있다. 일례로, 셀롤로스 등의 난용성의 물질의 특징을 이용하여 물과 함께 복용한 후 위장관에서 팽창하여 추가적인 음식물의 섭취를 저해하는 방법이 있으나, 이는 장시간 소화기계에 접촉하여 위장관 벽에 궤양을 일으키고, 무기염류에 대한 높은 흡착성으로 인하여 체내 무기염류의 흡수방해로 무기염류 저하를 일으켰으며, caffeine, ephedrine 등의 성분을 다량 함유한 천연물을 복용함으로 자율신경계의 활성을 증가시켜서 에너지 대사량을 늘려 체중감소를 유도하는 경우 위궤양 등의 일반적인 부작용 이외에도 변맥, 고혈압, 심계항진, 뇌졸중 등의 부작용이 있을 수 있다. 또한 지방흡수 차단제를 사용하는 경우 소화기관에서의 지방의 흡수를 차단하는 효과가 있으나 설사 등의 소화가계에서 일으키는 다양한 부작용 등이 있어 극히 제한된 사용만이 가능하며, 향정신성 의약품류에 의한 체중 감소제는 심장과 순환계 관련 부작용 및 다른 약물과 동시에 복용시 부작용을 나타낼 수 있어 의사의 처방 없이 사용이 불가능하다는 문제점이 있었다. In the case of diet, it is difficult to maintain a healthy body for a long time due to the lack of nutrients by increasing the intake of foods containing less fat or sugar, and the psychological burden due to the fasting or control of food is increased. In addition to the increase, stable metabolic rate, correction of insulin resistance and reduction of body fat have been shown to be effective. However, it is necessary to perform aerobic exercise for 20 minutes or more three times a week. By the way, exercise therapy may require effort, burden, discomfort, and endurance that are not normally required, and thus, there are many cases in which weight loss cannot be continued for a long time. Alternatively, when urgent treatment for extreme obesity is necessary, drug therapy or surgical therapy is performed, but the surgical therapy is very burdensome to the patient. Therapeutic drugs used in pharmacotherapy include digestive absorption inhibitors, anti-absorption inhibitors, or metabolic accelerators, but these drugs can put a burden on the human body and cause digestive problems. There is a problem that can not be used continuously for a long time. For example, there is a method of using the characteristics of poorly soluble substances such as cellulose to swell in the gastrointestinal tract and inhibit the intake of additional foods by taking it with water, but this causes contact with the digestive system for a long time and causes ulcers on the wall of the gastrointestinal tract. In addition, due to the high adsorption to inorganic salts, the absorption of inorganic salts in the body caused the inorganic salts to degrade, and by taking natural products containing large amounts of ingredients such as caffeine and ephedrine, the autonomic nervous system activity was increased to increase the energy metabolism, which leads to weight loss. Induced in addition to the usual side effects such as gastric ulcers may have side effects such as arrhythmia, hypertension, palpitations, stroke. In addition, the use of a fat absorption blocker has the effect of blocking the absorption of fat in the digestive tract, but there are various side effects such as diarrhea in the digestive system, so only limited use is possible, and weight loss agents due to psychotropic drugs Heart and circulatory side effects and side effects when taken at the same time with other drugs can not be used without a doctor's prescription.
상기와 같이 종래에는 비만치료를 위해 다양한 시도가 이루어져 왔지만, 아직까지는 안정성과 효능 및 심리적 부담감을 덜어줄 수 있는 치료법에 대한 발견이 거의 이루어지지 않았다. 따라서 천연물로서 식품으로 섭취가 가능하여 인체의 부담이 없으며, 치료시 지속적인 인내나 노력을 요구하지 않아 심리적 부담이 적으며, 장기간 사용되어 독성에 대한 안정성이 입증된 것 중에서 항비만 효과가 뛰어난 약물을 찾아내는 것이 효율적인 접근법이라 여겨진다.As described above, various attempts have been made for the treatment of obesity, but there have been few findings of treatments that can reduce the stability, efficacy, and psychological burden. Therefore, it can be consumed as food as a natural product, so there is no burden on the human body.There is no psychological burden because it does not require continuous patience or effort during treatment. Finding is considered an efficient approach.
한편, 유전적 소인, 비만 또는 식이 등으로 인한 고지혈증의 발생은 지방간, 심혈관계질환, 뇌졸중 발생의 빈도를 증가시킬 수 있다. 고지혈증의 치료제로서 전문의약품인 스타틴 (statin) 계열의 약물들이 주로 판매되고 있으나, 이러한 약물들은 횡문근 용해와 심장 등에 대한 부작용 등이 문제로 남아 있어 부작용 없는 고지혈증 치료제의 개발이 필요하다.On the other hand, the development of hyperlipidemia due to genetic predisposition, obesity, or diet may increase the frequency of fatty liver, cardiovascular disease, stroke. Statin-based drugs, which are specialty drugs, are mainly sold as drugs for hyperlipidemia, but these drugs require side effects such as rhabdomyolysis and heart problems. Therefore, it is necessary to develop hyperlipidemia drugs without side effects.
이에, 본 발명자들은 오랫동안 식용으로 섭취되어 안정성이 보장된 식물 유래의 다양한 한약재로부터 비만 및 고지혈증의 치료효과를 나타내는 약제를 찾고자 노력하였고, 이러한 약제의 생체 내 흡수율을 향상시키고 약제의 항 비만 및 항 고지혈 효능을 극대화시키기 위한 제법을 찾고자 노력하던 중, 항 비만 및 항 고지혈 효과를 보이는 약제를 발굴하고 이러한 약제의 생체 내 흡수율 및 안정성을 보장해 줄 수 있는 제법을 찾아냄으로 본 발명을 완성하였다.Accordingly, the present inventors have tried to find a drug that shows the therapeutic effect of obesity and hyperlipidemia from various herbal medicines derived from plants, which have been ingested for a long time and are guaranteed stability, and improve the absorption rate of such drugs in vivo and anti-obesity and anti-hyperlipidemia of the drug. While trying to find a method for maximizing efficacy, the present invention was completed by discovering drugs that exhibit anti-obesity and anti-hyperlipidemic effects and finding a method that can ensure the absorption and stability of such drugs in vivo.
본 발명은 지골피, 창출, 상심자를 포함하는 한약재의 발효물 또는 발효물의 추출물을 유효성분으로 함유하는 비만 또는 고지혈증의 예방 및 치료용 조성물을 제공하는 데 있다.The present invention is to provide a composition for the prevention and treatment of obesity or hyperlipidemia, containing the fermentation of herbal medicine or extract of the fermentation including the phalanges, creation, loser.
또한, 본 발명은 지골피, 창출, 상심자를 포함하는 한약재의 발효물 또는 발효물의 추출물을 유효성분으로 함유하는 비만 또는 고지혈증의 예방 및 치료용 약학 조성물 및 지골피, 창출, 상심자를 포함하는 한약재의 발효물 또는 발효물의 추출물을 유효성분으로 함유하는 비만 또는 고지혈증의 예방 및 치료용 건강식품을 제공하는데 있다. In addition, the present invention is a pharmaceutical composition for the prevention and treatment of obesity or hyperlipidemia, containing the fermentation product of herbal medicine or extract of fermentation, including the phalanges, creation, and loser as an active ingredient and the fermentation of Chinese medicine, including the phalanges, creation, loser Or to provide a health food for the prevention and treatment of obesity or hyperlipidemia containing the extract of the fermented product as an active ingredient.
본 발명은 한약재 발효물 또는 발효물의 추출물을 유효성분으로 포함한 비만 또는 고지혈증의 예방 및 치료용 조성물에 관한 것이다. The present invention relates to a composition for the prevention and treatment of obesity or hyperlipidemia, including the herbal medicine fermented product or extract of the fermented product as an active ingredient.
또한, 본 발명은 한약재 발효물 또는 발효물의 추출물을 유효성분으로 포함한 비만 또는 고지혈증의 예방 및 치료용 건강식품 및 비만 또는 고지혈증의 예방 및 치료용 약학 조성물에 관한 것이다. In addition, the present invention relates to a health food for the prevention and treatment of obesity or hyperlipidemia, and a pharmaceutical composition for the prevention and treatment of obesity or hyperlipidemia, including the herbal medicine fermented product or extract of the fermented product as an active ingredient.
이하 본 발명에 대하여 보다 상세히 설명한다.Hereinafter, the present invention will be described in more detail.
본 발명에서 사용되는 기술 용어 및 과학 용어에 있어서 다른 정의가 없다면, 이 발명이 속하는 기술 분야에서 통상의 지식을 가진 자가 통상적으로 이해하고 있는 의미를 갖는 것으로 해석될 수 있다.Unless otherwise defined in the technical and scientific terms used in the present invention, it can be interpreted as having a meaning commonly understood by those skilled in the art.
본 발명에 있어서, 지골피는 구기자나무의 뿌리로서, 몸이 허약하여 생기는 식은땀, 해수, 천식, 토혈, 코피, 소변출혈, 고혈당, 고혈에 좋으며 신경통, 두통, 어깨통증, 근육통, 요통, 허리와 무릎의 무력감이 있는 경우에 사용하며, 정혈 부족 때 상대적으로 일어나는 허약성 미열, 즉 허열의 치료에 사용되는 약재로 알려져 있다.In the present invention, the phalanges are roots of goji berry, good for cold sweat, seawater, asthma, hemostasis, nosebleed, urine bleeding, high blood sugar, high blood pressure, neuralgia, headache, shoulder pain, muscle pain, back pain, waist and It is used when there is a feeling of helplessness of the knee, and it is known as a medicine used for the treatment of fragile mild fever, ie, fever, which occurs relatively when lack of blood.
본 발명에 있어서, 창출은 삽주뿌리로서 맛은 약간 방향성 (박하처럼 화하다는 느낌)이 있으며 쓴맛이고 성질은 따뜻한 편에 속하며, 소화기계 장관내에 고이는 유동성 체액을 조절해 주고 비위장을 강하게 한다고 알려져 있으며, 또한 관절통이나 하지무력, 전신동통에 효과가 있다고 알려져 있다.In the present invention, the creation is a shoveling root, taste is slightly aromatic (feeling like peppermint), bitter taste and belonging to the warm side, it is known to control fluid fluids in the gastrointestinal tract and strengthen the spleen, It is also known to be effective on joint pain, lower limb strength and general pain.
본 발명에 있어서 상심자는 까맣게 익은 뽕나무 열매인 오디로서, 오디는 많이 먹으면 머리가 검게된다고 하는 자양강장의 효과가 있으며 청색에서 차츰 붉어져 완전히 익으면 자주색에서 흑색으로 변한다. 피를 굉장히 깨끗하게 만들어주어 늙지 않는 약으로 알려져 있으며, 간과 신장을 도와 음혈 (陰血)을 보하여 진액이 고갈되어 생기는 소갈증 (당뇨)을 다스리며, 입안이 건조하고 혀가 마르는 증상과 간음부족으로 인한 어지럼증, 불면에 효과가 있다. 또한 장을 부드럽게하며 혈부족으로 오는 변비에 효과가 있는 약재로 알려져 있다. In the present invention, the heart of the mulberry is mulberry ripe mulberry fruit, Audi has the effect of nourishing tonic that the hair is black when eaten a lot and gradually turns red from blue to purple to black. It is known as a medicine that does not grow old because it makes blood very clean.It helps the liver and kidneys to treat bleeding, which helps to treat the small thirst (diabetes) caused by depletion of the essence, dry mouth, dry tongue and lack of adultery. It is effective for dizziness and insomnia. It is also known as a medicine that is effective in constipation and softens the intestines, which leads to lack of blood.
이하, 본 발명에서는 지골피, 창출, 상심자로 구성된 약재를 삼정환이라 명명하겠다.Hereinafter, in the present invention, the medicine consisting of phalanges, creation, heartache will be named Samjeonghwan.
본 발명은 지골피, 창출, 상심자를 포함하는 한약재 발효물 또는 발효물의 추출물을 유효성분으로 함유하는 비만 또는 고지혈증의 예방 및 치료용 조성물에 관한 것으로, 상기 창출, 지골피, 상심자의 중량은 특별히 한정되는 것은 아니나, 바람직하게는 창출의 중량부를 10으로 둘 경우, 지골피의 중량부는 8 내지 12, 상심자의 중량부는 18 내지 22로 약재를 포함할 수 있다.The present invention relates to a composition for the prevention and treatment of obesity or hyperlipidemia comprising the phalanx, phalanx, extract, fermented extract of fermented products, or as an active ingredient, the weight of the creation, phalanges, and loser is specifically limited However, preferably when the weight of the creation is set to 10, the weight of the phalanges may include 8 to 12, the weight of the heartache 18 to 22 may include the medicine.
본 발명의 지골피, 창출, 상심자가 포함된 약재를 발효시키는 방법은 당업계에서 통상적으로 수행하는 방법으로 할 수 있으나, 바람직하게는 창출, 지골피를 마쇄한 후, 상기 상심자를 생으로 즙을 짜서 마쇄된 지골피, 창출과 혼합하여 발효시킨다. 상기 발효기간은 상온에서 발효시킬 경우 20일 내지 50일, 바람직하게는 25 내지 35일이 적당할 수 있다. The method of fermenting the medicinal herbs containing the phalanges, creation, heartache of the present invention may be a method commonly performed in the art, but preferably, after the creation, grinding the phalanges, the heartache is crushed by squeezing juice raw Phalanges, mixed with the creation fermentation. When the fermentation period is fermented at room temperature 20 to 50 days, preferably 25 to 35 days may be appropriate.
본 발명은 발효과정을 통해 상기 약제를 인체 세포에 흡수가 용이한 저분자 물질로 전환하거나 발효과정 시 미생물이 가지고 있는 효소를 이용하여 유기물을 분해시켜서 인체에 유용한 물질을 부가적으로 생성함으로 약제의 항 비만 효능을 월등히 증가시켰을 뿐만 아니라, 장내 면역 및 독소제거 (detoxification) 기능을 수행할 수도 있다.The present invention converts the drug into a low-molecular substance that is easily absorbed by human cells through a fermentation process or by additionally generating a useful material for the human body by decomposing organic substances using enzymes that microorganisms have during fermentation. Not only did it significantly increase obesity efficacy, it could also perform intestinal immunity and detoxification functions.
본 발명의 바람직한 일례로, 상기 발효물을 제조하는데 사용되는 균주로는 발효물 중에서 우점종을 차지하는 균주 중 분리된 것으로, 비피오박테리움 롱검 (Bifidobacterium longum)과 비피오박테리움 브레브 (Bifidobacterium breve)로 이루어진 군으로부터 선택된 미생물일 수 있다.In a preferred embodiment of the present invention, the strain used to prepare the fermentation is isolated from the strains occupying the dominant species in the fermentation, Bifidobacterium longum (Bifidobacterium longum) and Bifidobacterium breve (Bifidobacterium breve) It may be a microorganism selected from the group consisting of.
본 발명의 바람직한 일례로, 상기 발효물을 제조하는데 사용되는 균주로는 유산균과 효모로 이루어진 군으로부터 선택된 미생물일 수 있으며, 바람직하게는 상기 유산균은 김치로부터 분리한 Lactobacillus plantarum P23 균주일 수 있으며, 상기 효모는 맥주 발효 균주인 Yeast DSII일 수 있으나 이에 한정되는 것은 아니다.In a preferred embodiment of the present invention, the strain used to prepare the fermentation may be a microorganism selected from the group consisting of lactic acid bacteria and yeast, preferably the lactic acid bacteria may be Lactobacillus plantarum P23 strain isolated from kimchi, Yeast may be Yeast DSII, a beer fermentation strain, but is not limited thereto.
선택적으로, 상기 발효물을 그대로 사용할 수도 있고, 상기 발효물을 추출하여 당해 발효물의 추출물을 유효성분으로 함유하는 비만 또는 고지혈증의 예방 및 치료용 조성물을 제공할 수 있다. 상기 발효된 약재의 중량의 약 0.5배 내지 10배, 바람직하게는 2배 내지 6 부피의 물, 메탄올, 에탄올, 부탄올 등과 같은 C1 내지 C4의 저급 알콜 또는 이들의 약 1:0.1 내지 1:10의 혼합비를 갖는 혼합용매, 바람직하게는 메탄올을 사용할 수 있으며, 상기 용매는 5 내지 100%, 바람직하게는 80 내지 100%일 수 있다. 추출시간은 1시간 내지 48시간, 바람직하게는 12시간 내지 36시간 동안 열수 추출, 냉침 추출, 환류 냉각 추출 또는 초음파 추출, 바람직하게는 열수 추출할 수 있으며, 상기 열수 추출온도는 특별히 한정된 것은 아니나 바람직하게는 40 내지 80℃, 더욱 바람직하게는 50 내지 70℃로 추출할 수 있는데, 상기 추출은 반복하여 시행될 수 있다. 상기 추출시간 및 온도에 있어서, 상기 추출온도를 높이면 추출시간은 줄어들 수 있지만 지나치게 높은 온도는 발효된 약재 내의 유용한 균들을 파괴하여 약제의 체내 흡수율을 감소시킬 수 있고 약재가 인체의 장내에서 생성하는 유용한 물질 생성력 및 장내 면역 및 독소 제거력이 감소 될 수 있으며, 상기 추출온도가 지나치게 낮으면 추출시간이 증가하며 상기 약제의 유효성분이 완전하게 추출되지 않을 수 있다는 문제점이 있다. 상기 추출물을 냉각시키고 감압여과 및 농축하여 본 발명에서 이용 가능한 추출물을 수득할 수 있다. Optionally, the fermented product may be used as it is, and the fermented product may be extracted to provide a composition for the prevention and treatment of obesity or hyperlipidemia containing the extract of the fermented product as an active ingredient. About 0.5 to 10 times the weight of the fermented medicinal herbs, preferably 2 to 6 volumes of water, C1 to C4 lower alcohols such as methanol, ethanol, butanol and the like, or about 1: 0.1 to 1:10 A mixed solvent having a mixing ratio, preferably methanol, may be used, and the solvent may be 5 to 100%, preferably 80 to 100%. The extraction time may be hot water extraction, cold needle extraction, reflux cooling extraction or ultrasonic extraction, preferably hot water extraction for 1 hour to 48 hours, preferably 12 hours to 36 hours, and the hot water extraction temperature is not particularly limited. Preferably it can be extracted at 40 to 80 ℃, more preferably 50 to 70 ℃, the extraction may be carried out repeatedly. In the extraction time and temperature, the extraction time can be reduced by increasing the extraction temperature, but excessively high temperature can destroy useful bacteria in fermented medicinal herbs to reduce the absorption rate of the medicament, Substance generation and intestinal immunity and toxin removal may be reduced. If the extraction temperature is too low, the extraction time increases and there is a problem that the active ingredient of the drug may not be completely extracted. The extract can be cooled, filtered and concentrated under reduced pressure to obtain an extract usable in the present invention.
본 발명은 지골피, 창출, 상심자를 포함하는 발효물 또는 발효물의 추출물을 유효성분으로 함유하는 비만 또는 고지혈증의 예방 및 치료용 약학 조성물을 제공한다.The present invention provides a pharmaceutical composition for the prevention and treatment of obesity or hyperlipidemia, including the phalanx, the production, the fermented product including the loser or extract of the fermented product as an active ingredient.
본 발명의 발효물 또는 발효물의 추출물을 포함하는 약학조성물은 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다. 본 발명에 따른 발효물 또는 발효물의 추출물을 포함하는 비만 또는 고지혈증의 예방 및 치료용 약학조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. 당해 기술 분야에 알려진 적합한 제제는 문헌 (Remington's Pharmaceutical Science, 최근, Mack Publishing Company, Easton PA)에 개시되어 있는 것을 사용하는 것이 바람직하다. 발효물 또는 발효물의 추출물을 포함하는 약학조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 발효물 또는 발효물의 추출물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트 (calcium carbonate), 수크로 스 (sucrose) 또는 락토오스 (lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜 (propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔 (witepsol), 마크로골, 트윈 (tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다. The pharmaceutical composition comprising the fermentation product or extract of the fermentation product of the present invention may further include appropriate carriers, excipients and diluents commonly used in the preparation of pharmaceutical compositions. Pharmaceutical compositions for the prevention and treatment of obesity or hyperlipidemia comprising fermented products or extracts of fermented products according to the present invention, respectively, oral powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like according to conventional methods It may be used in the form of a dosage form, an external preparation, a suppository, and a sterile injectable solution. Suitable formulations known in the art are preferably those disclosed in Remington's Pharmaceutical Science, recently, Mack Publishing Company, Easton PA. Carriers, excipients and diluents which may be included in the pharmaceutical composition comprising fermented products or extracts of fermented products include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin , Calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient, for example, starch, calcium carbonate, in the fermentation or extract of the fermentation product. Prepared by mixing sucrose or lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
본 발명의 상기 발효물 또는 발효물의 추출물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나, 바람직한 효과를 위해서, 본 발명의 발효물 또는 발효물의 추출물은 1일 0.0001 내지 100 ㎎/㎏으로, 바람직하게는 0.001 내지 100 ㎎/㎏으로 투여하는 것이 좋으나, 환자의 상태 등에 따라 투여량이 변화할 수도 있다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.The preferred dosage of the fermentation or extract of the fermentation of the present invention depends on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. However, for the desired effect, the fermentation product or the extract of the fermentation product of the present invention is preferably administered at 0.0001 to 100 mg / kg, preferably 0.001 to 100 mg / kg, but the dosage is changed depending on the condition of the patient. You may. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect.
본 발명의 상기 발효물 또는 발효물의 추출물은 쥐, 생쥐, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁 내 경막 또는 뇌혈관 내 (intracerebroventricular) 주사에 의해 투여될 수 있다. The fermentation product or extract of the fermentation product of the present invention can be administered to various mammals such as mice, mice, livestock, humans. All modes of administration can be expected, for example by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.
본 발명은 지골피, 창출, 상심자를 포함하는 한약재의 발효물 또는 발효물의 추출물을 유효성분으로 함유하는 비만 또는 고지혈증의 예방 및 치료용 건강식품을 제공한다.The present invention provides a health food for the prevention and treatment of obesity or hyperlipidemia, containing the fermentation product of herbal medicine or extract of the fermentation product including phalanx, jingolpi, creation heartache.
본 발명의 발효물 또는 발효물의 추출물은 비만 또는 고지혈증의 예방 및 치료용 건강식품 및 음료 등에 다양하게 이용될 수 있다. 본 발효물또는 발효물의 추출물을 첨가할 수 있는 식품으로는, 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 건강 식품류 등이 있다. 본 발명의 발효물 또는 발효물의 추출물은 독성 및 부작용은 거의 없으므로 예방 목적으로 장기간 복용시에도 안심하고 사용할 수 있다. 본 발명의 발효물 또는 발효물의 추출물은 식품 또는 음료에 첨가될 수 있다. 이때, 식품 또는 음료 중의 발효물 또는 발효물의 추출물의 양은 전체 식품 중량의 0.01 내지 50 중량%로 가할 수 있으며, 건강 음료는 100 ㎖를 기준으로 0.02 내지 30 g, 바람직하게는 0.3 내지 10 g의 비율로 가할 수 있다.Fermentation products or extracts of the fermentation products of the present invention can be used in a variety of health foods and beverages for the prevention and treatment of obesity or hyperlipidemia. Examples of the food to which the present fermented product or extract of the fermented product can be added include various foods, beverages, gums, teas, vitamin complexes, and health foods. Fermented product or extract of the fermented product of the present invention has little toxicity and side effects, so can be used with confidence even for long-term use for the purpose of prevention. Fermentation products or extracts of the fermentation products of the present invention may be added to food or beverage. At this time, the amount of the fermentation product or the extract of the fermentation product in the food or beverage may be added to 0.01 to 50% by weight of the total food weight, the health beverage is 0.02 to 30 g, preferably 0.3 to 10 g based on 100 ml Can be added.
본 발명의 건강 음료는 지시된 비율로 필수 성분으로서 상기 발효물 또는 발효물의 추출물을 함유하는 외에는 다른 성분에는 특별한 제한이 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제 (타우마틴), 스테비아 발효물 (예를 들어 레바우디오시드 A, 글리시르히진 등) 및 합성 향미제 (사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 발효물 또는 발효물의 추출물 100 ㎖당 일반적으로 약 1 내지 20g, 바람직하게는 약 5 내지 12g이다.The health beverage of the present invention is not particularly limited to other ingredients except for containing the fermented product or extract of the fermented product as essential ingredients in the indicated ratios, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. Can be. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin), stevia fermentation products (e.g., Rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) are advantageously used. Can be. The proportion of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the fermentation product or extract of the fermentation product of the present invention.
상기 외에 본 발명의 발효물 또는 발효물의 추출물은 여러 가지 영양제, 비타민, 광물 (전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제 (치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 발효물 또는 발효물의 추출물들은 천연 과일 쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만, 본 발명의 발효물 또는 발효물의 추출물 100 중량부 당 0 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the fermented products or extracts of the fermented products of the present invention include various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors such as flavoring agents, colorants and neutralizing agents (cheese, chocolate, etc.), pectic acid and its Salts, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks and the like. In addition, the fermentation products or extracts of the fermentation products of the present invention may contain the flesh for the production of natural fruit juice and fruit juice beverage and vegetable beverage. These components can be used independently or in combination. The proportion of such additives is not so critical, but is generally selected from the range of 0 to about 20 parts by weight per 100 parts by weight of the fermentation product or extract of the fermentation product.
본 발명은 창출, 지골피, 상심자를 포함하는 한약재의 발효물 또는 발효물의 추출물을 유효성분으로 함유하는 비만 또는 고지혈증의 예방 및 치료용 조성물을 제공한다. 본 발명의 조성물은 항비만 및 항고지혈의 효과가 뛰어날 뿐 아니라 생체내 흡수율 및 독성이나 부작용 없고 안전성이 우수하기에 이를 이용하여 의약품 및 건강식품으로 사용할 수 있을 것이다.The present invention provides a composition for the prevention and treatment of obesity or hyperlipidemia, containing the fermentation product of herbal medicine or extract of the fermentation product including phalanx, phalanx, heartache as an active ingredient. The composition of the present invention will not only be excellent in the effects of anti-obesity and anti-hyperlipidemia, but also can be used as a medicine and health food using it because of its excellent safety in vivo absorption and no toxicity or side effects.
도 1은 웨스턴블롯을 이용하여 3T3-L1 cell에서의 지방분화 관련 단백질 PPAR-r을 정량한 실험의 결과이다. 다섯가지 유산균주로서 삼정환을 발효시켰는데 전반적으로 억제되는 효과가 있었고 특히 FH1과 FH2에서 용량의존적으로 PPARr 발현이 억제됨을 관찰할 수 있었다.1 is a result of an experiment for quantifying the lipodifferentiation related protein PPAR-r in 3T3-L1 cells using Western blot. The fermentation of Samjunghwan as five lactic acid strains showed overall suppression effect, and in particular, dose-dependent PPARr expression was inhibited in FH1 and FH2.
도 2는 3T3-L1 cell에서의 지방분화 관련 유전자인 PPAR-r 및 CEBPa의 발현을 real time PCR에서 관찰한 결과와 열발생과 관련되는 UCP-2 단백질을 정량평가한 그래프이다. FH2 고용량에서 가장 뚜렷한 결과를 보였다.Figure 2 is a graph of quantitative evaluation of the results of observing the expression of PPAR-r and CEBPa, adifferentiation-related genes in 3T3-L1 cells by real time PCR, and the UCP-2 protein associated with heat generation. The most pronounced results were obtained at high doses of FH2.
도 3은 3T3-L1 preadipocyte 분화 전후 염증 및 지방세포분화 관련 mRNA 발현량 차이를 나타낸 것으로, 발효 전 삼정환과 발효 후 삼정환의 지방세포분화 관련 mRNA 발현량 차이를 나타낸 것이다.Figure 3 shows the difference in the mRNA expression level between inflammation and adipocyte differentiation before and after 3T3-L1 preadipocyte differentiation, and shows the difference in the amount of mRNA expression related to adipocyte differentiation of Samjunghwan before fermentation and Samjeonghwan after fermentation.
도 4a는 일반사료를 먹인 정상군 (normal)과, 고지방사료를 먹인 비만유발군 (HFD) 및 고지방사료를 먹이고 발효삼정환을 투여한 비만+삼정환군 (HFD+SJH)의 체중변화를 나타낸 것이다. Figure 4a shows the change in body weight of the normal group fed normal feed (normal), obesity-induced group fed high fat feed (HFD) and obese + samjeonghwan group fed high fat feed and fermented samjunghwan (HFD + SJH) .
도 4b는 일반사료를 먹인 정상군 (normal)과, 고지방사료를 먹인 비만유발군 (HFD) 및 고지방사료를 먹이고 발효삼정환을 투여한 비만+삼정환군 (HFD+SJH)의 심장, 비장, 신장, 간장, 부고환지방, 복부내장지방의 무게를 측정한 것이다. Figure 4b shows the heart, spleen and kidney of the normal group fed normal feed (normal), the obesity-induced group fed high fat feed (HFD) and the obesity + samjunghwan group (HFD + SJH) fed high fat feed and fermented samjunghwan , Liver, epididymal fat, and abdominal visceral fat were measured.
도 4c는 일반사료를 먹인 정상군 (normal)과, 고지방사료를 먹인 비만유발군 (HFD) 및 고지방사료를 먹이고 발효삼정환을 투여한 비만+삼정환군 (HFD+SJH)의 혈중 중성지방, 혈중 고밀도지단백, 혈중 저밀도지단백의 차이를 나타낸 것이다.Figure 4c shows normal triglycerides in the normal group fed normal feed, obesity-induced group fed high fat feed (HFD), and obese + samjeonghwan group fed high fermented samjunghwan (HFD + SJH). It shows the difference between high density lipoprotein and low density lipoprotein in blood.
도 5는 각 배지별 미생물 검출사진을 나타낸 것이다.Figure 5 shows a microbial detection photograph for each medium.
도 6은 각 배지별 미생물 현미경 검경 사진을 나타낸 것이다.Figure 6 shows a microscopic microscope image of each medium.
도 7은 발효 한약재 삼정환 분말에 존재하는 균주를 나타낸 것이다.Figure 7 shows the strain present in the fermented herbal medicine Samjunghwan powder.
도 8은 자연발효 삼정환, Lactobacillus plantarum P23의 발효 삼정환, Yeast DSII의 발효 삼정환, Lactobacillus plantarum P23와 Yeast DSII의 발효 삼정환의 총 발효기간 동안의 발효 균주별 pH 변화를 나타낸 것이다.Figure 8 shows the pH change of the fermentation strains during the total fermentation period of three fermentation of three fermentation of three fermentation of three fermentation of three fermentation of three fermentation, three fermentation of Lactobacillus plantarum P23, three fermentation of Yeast DSII, three fermentation of Lactobacillus plantarum P23 and Yeast DSII.
도 9는 자연발효 삼정환, Lactobacillus plantarum P23의 발효 삼정환, Yeast DSII의 발효 삼정환, Lactobacillus plantarum P23와 Yeast DSII의 발효 삼정환의 2일 동안의 발효 균주별 pH 변화를 나타낸 것이다.Figure 9 shows the pH change of the fermentation strain for two days of three fermentation of three fermentation of three fermentation of three fermentation of three fermentation of three fermentation of three fermentation, three fermentation of Lactobacillus plantarum P23, three fermentation of Yeast DSII, three fermentation of Lactobacillus plantarum P23 and Yeast DSII.
도 10은 자연발효 삼정환, Lactobacillus plantarum P23의 발효 삼정환, Yeast DSII의 발효 삼정환, Lactobacillus plantarum P23와 Yeast DSII의 발효 삼정환의 발효시 환원당 변화를 나타낸 것이다.Figure 10 shows the changes in reducing sugars during fermentation of three fermentation of three fermentation of three fermentation of three fermentation of three fermentation of three fermentation, three fermentation of fermentation of Lactobacillus plantarum P23, three fermentation of fermentation of Yeast DSII, three fermentation of Lactobacillus plantarum P23.
도 11은 유산균 (B. longum, E. faecium, P. pentosaceus)에 의한 삼정환 약재의 발효 전후의 크로마토그램 (UV 254 nm 분석결과)을 나타낸 것이다. 아직까지 어떤 물질이 지방합성 억제효과를 나타내는지 알 수는 없지만 적어도 발효전후로 많은 유효물질의 변화가 있음을 확인할 수 있다.
11 shows chromatograms (UV 254 nm analysis results) before and after fermentation of Samjunghwan medicinal products by lactic acid bacteria ( B. longum, E. faecium, P. pentosaceus) . It is not yet known which substances have the effect of inhibiting fat synthesis, but at least before and after fermentation, there are many active substance changes .
도 12는 유산균 (L. acidophilus P23)에 의한 삼정환 약재 발효 전후의 크로마토그램 (UV 254 nm 분석결과)을 나타낸 것이다.Figure 12 shows the lactic acid bacteria (L. acidophilus P23) Samjeong ring medicine fermentation chromatogram (UV 254 nm analysis) of the front and rear by.
도 13은 유산균 (L. plantarum P23)에 의한 삼정환 약재 발효 전후의 크로마토그램 (UV 254 nm 분석결과)을 나타낸 것이다.Figure 13 shows the lactic acid bacteria (L. plantarum P23) Samjeong ring medicine fermentation chromatogram (UV 254 nm analysis) of the front and rear by.
도 14는 다섯가지 유산균주로 발효시킨 삼정환의 지방세포 분화 억제능을 나타낸 것이다.Figure 14 shows the ability to inhibit the differentiation of fat cells of Samjunghwan fermented with five lactic acid strains.
도 15는 C57BL/6 마우스에서 Lactobacillus plantarum P23이 혈중 고밀도지단백 및 저밀도지단백의 콜레스테롤 및 중성지방의 레벨에 미치는 영향에 관한 것이다 (Data are mean6SEM. *P < 0.05 compared with controls. C, control group; HDL, high-density lipoprotein; LDL, low-density lipoprotein; PD, group fed dead bacteria; PL, group fed live bacteria.).15 shows the effect of Lactobacillus plantarum P23 on the levels of cholesterol and triglycerides of high density lipoprotein and low density lipoprotein in blood in C57BL / 6 mice (Data are mean 6 SEM. * P <0.05 compared with controls. C, control group; HDL , high-density lipoprotein; LDL, low-density lipoprotein; PD, group fed dead bacteria; PL, group fed live bacteria.).
본 발명은 이하 실시예, 실험예 및 제제예로써 상세히 설명하지만, 본 발명의 기술적 범위가 이들 실시예, 실험예 및 제제예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실시예, 실험예 및 제제예에 의해 한정되는 것은 아니다.The present invention will be described in detail by the following Examples, Experimental Examples and Formulation Examples, but the technical scope of the present invention is that these Examples, Experimental Examples and Formulation Examples are merely illustrative of the present invention, the contents of the present invention are the following Examples, It is not limited by the experiment example and preparation example.
실시예 1: 비발효 삼정환과 발효 삼정환의 제조방법Example 1: Preparation of Nonfermented Samjunghwan and Fermented Samjeonghwan
1) 발효되지 않은 본 발명의 조성물은 창출, 지골피 각각 600g을 갈아서 가루로 만들고, 상심자 1200g를 생으로 짜서 즙으로 만들어, 여기에 앞서 가루 낸 창출, 지골피를 넣어 고루 섞은 후 환으로 제조하였다.1) The composition of the present invention that is not fermented was produced by grinding 600 g of each of the phalanges, phalanges, and made into juice by squeezing the freshener 1200 g into raw materials.
2) 발효된 본 발명의 조성물은 창출, 지골피 각각 600g을 갈아서 가루로 만들고, 상심자 1200g를 생으로 짜서 즙으로 만들어, 여기에 앞서 가루 낸 창출, 지골피를 넣어 고루 섞은 후 옹기 내에서 밀봉상태로 상온에서 35일간 발효시킨 후 환으로 제조하였다.2) The fermented composition of the present invention is made by grinding 600 g of each of the phalanges, phalanges, and powder, and squeezed 1200 g of raw heartwood into juice. After fermentation in 35 days was prepared in a ring.
3) 상기 환 245g을 잘게 분쇄하여, 이에 3배량의 95% 메탄올을 가하고 60℃에서 중탕으로 24시간씩 3회 추출하여 추출액을 얻은 후, 이 추출액을 실온으로 냉각시키고 여지로 여과한 다음 여액을 회전 감압 농축기를 사용하여 건조시켜 추출물21.8g (수율8.9%)를 얻어 실험에 사용하였다.3) Grind 245 g of the ring finely, add three times the amount of 95% methanol and extract it three times for 24 hours at 60 ° C. with a hot bath to obtain an extract. The extract is cooled to room temperature and filtered through a filtrate. Drying was carried out using a rotary vacuum concentrator to obtain 21.8 g of an extract (yield 8.9%), which was used in the experiment.
실험예 1: 비발효 삼정환과 발효 삼정환의 항비만효과 비교Experimental Example 1: Comparison of anti-obesity effect between non-fermented Samjung-hwan and fermented Samjeong-hwan
실험예1-1 : 세포주와 세포배양Experimental Example 1-1: Cell Line and Cell Culture
실험에 사용한 pre-adipocyte인 3T3 L-1 세포는 American Type Culture Collection (Rockville, MD, USA) 에서 구입을 하였다. 세포는 37℃, 5% CO2 incubator에서 10% Fetal Bovine Serum (FBS; Invitrogen, USA)이 함유된 DMEM (Invitrogen, USA) 배지를 사용하여 배양하였다. 오염 방지를 위해 항생제로 100unit/ml penicillin, 100ug/ml streptomycin (Gibco/BRL, USA)을 첨가하였다. Trypsin-EDTA (Gibco/BRL, USA)를 처리하여 계대 배양하였다. 배지는 2-3일 마다 교환하여 주었다. 지방세포로 분화시키기 위해 1X105/well 의 개수로 6-well plate (Corning, USA) 에 옮겨주고 10μg/ml Insulin, 0.25μM Dexamethasone, 0.5mM IBMX 이 들어간 1차 분화배지로 교환해주고 48시간 후에 2차 분화배지인 5μg/ml Insulin이 들어간 배지에서 지방세포로 분화를 6일간 유도한다. 배지는 2일 간격으로 새 배지로 교환해 주었다. 세포에 처리하는 농도는 발효전 및 발효 삼정환을 각각 500, 1000 배로 희석해서 세포에 처리하였다. The pre-adipocyte 3T3 L-1 cells used in the experiment were purchased from the American Type Culture Collection (Rockville, MD, USA). Cells were cultured in DMEM (Invitrogen, USA) medium containing 10% Fetal Bovine Serum (FBS; Invitrogen, USA) in a 37 ° C., 5% CO 2 incubator. To prevent contamination, 100 units / ml penicillin and 100 ug / ml streptomycin (Gibco / BRL, USA) were added as antibiotics. Subsequent passages were treated with Trypsin-EDTA (Gibco / BRL, USA). The medium was changed every 2-3 days. To differentiate into adipocytes, transfer to a 6-well plate (Corning, USA) in the number of 1 × 10 5 / well and exchange with a primary differentiation medium containing 10 μg / ml Insulin, 0.25 μM Dexamethasone, 0.5 mM IBMX Induce differentiation into adipocytes for 6 days in medium containing 5μg / ml Insulin, a differentiation medium. The medium was replaced with fresh medium every two days. The concentration of the cells was treated by diluting 500 and 1000 times the fermentation and fermented Samjunghwan, respectively, to the cells.
실험예1-2 : 웨스턴블롯과 RT PCR을 이용한 3T3-L1 cell에서의 지방분화 관련 단백질 정량 Experimental Example 1-2: Determination of Lipoprotein - related Proteins in 3T3-L1 Cells by Western Blot and RT PCR
도 1의 결과 FH1과 FH2에서 용량의존적으로 PPARr 발현이 억제됨을 관찰할 수 있었다. As a result of FIG. 1, it was observed that PPARr expression was inhibited in dose-dependent manner in FH1 and FH2.
Real time PCR에서 관찰한 PPARr 유전자 발현 및 FH2 고용량에서 가장 뚜렷한 결과를 보였다 (도 2). 이러한 결과를 활용하여 향후 in vivo test에 사용할 균주를 결정하고자 하였다.The PPARr gene expression observed in real time PCR and the FH2 high dose showed the most distinct result (FIG. 2). These results were used to determine the strain to be used in future in vivo test.
실험예1-3 : 3T3-L1 preadipocyte 분화 전후 염증 및 지방세포분화 관련 mRNA 발현량 차이 Experimental Example 1-3: Differences in mRNA Expression Related to Inflammation and Adipocyte Differentiation Before and After 3T3-L1 Preadipocyte Differentiation
지방세포 분화에 관련된 PPAR-gamma, SREBP-1c, TNF-alpha 유전자의 발현 정도를 Real time PCR 법을 사용하여 관찰하였다. 분화된 지방세포에 두 농도의 삼정환과 발효 삼정환 농축물을 넣고 24시간이 지난 후 세포에서 RNA를 Trisol (Invitrogen, USA)을 이용하여 추출하여 cDNA를 합성한 후 아래의 primer를 이용하여 real time PCR (Light cycler 480, Boeringer Manheim, Germany) 을 수행하였으며 beta-actin으로 각 유전자의 발현정도를 계산하였다.The expression levels of PPAR-gamma, SREBP-1c and TNF-alpha genes involved in adipocyte differentiation were observed using real time PCR. After 24 hours, two concentrations of Samjunghwan and fermented Samjunghwan concentrates were differentiated into differentiated adipocytes. RNA was extracted from the cells using Trisol (Invitrogen, USA) to synthesize cDNA. PCR (Light cycler 480, Boeringer Manheim, Germany) was performed and the expression level of each gene was calculated with beta-actin.
표 1
Table 1
Gene name | Direction | sequence |
PPAR-gamma | Forward | 5'-GAG ATG CCA TTC TGG CCC ACC AAC TTC GG-3' |
Reverse | 5'-TAT CAT AAA TAA GCT TCA ATC GGA TGG TTC-3' | |
SREBP-1c | Forward | 5'- ATC GGC GCG GAA GCT GTC GGG GTA GCG TC-3' |
Reverse | 5'- ACT GTC TTG GTT GTT GAT GAG CTG GAG CAT-3' | |
TNF-alpha | Forward | 5'-AGG CCT TGT GTT GTG TTT CCA-3' |
Reverse | 5'-TGG GGG ACA GCT TCC TTC TT-3' |
Gene name | Direction | sequence |
PPAR-gamma | Forward | 5'-GAG ATG CCA TTC TGG CCC ACC AAC TTC GG-3 ' |
Reverse | 5'-TAT CAT AAA TAA GCT TCA ATC GGA TGG TTC-3 ' | |
SREBP-1c | Forward | 5'- ATC GGC GCG GAA GCT GTC GGG GTA GCG TC-3 ' |
Reverse | 5'- ACT GTC TTG GTT GTT GAT GAG CTG GAG CAT-3 ' | |
TNF-alpha | Forward | 5'-AGG CCT TGT GTT GTG TTT CCA-3 ' |
Reverse | 5'-TGG GGG ACA GCT TCC TTC TT-3 ' |
도 3에서 나타난 바와 같이, 일반 발효되지 않은 삼정환에 비해 발효된 삼정환을 주입하였을 때, 지방세포 분화에 관련된 PPAR-gamma, SREBP-1c, TNF-alpha 유전자의 발현정도가 확연하게 감소됨을 확인함으로써 본 발명의 발효삼정환이 일반 발효되지 않은 삼정환에 비해 항비만 효과가 우수함을 알 수 있었다.As shown in FIG. 3, when the fermented samjung-hwan was injected compared to the non-fermented samjung-hwan, the expression levels of PPAR-gamma, SREBP-1c and TNF-alpha genes related to adipocyte differentiation were significantly reduced. As a result, it was found that the fermented samjung hwan of the present invention has an excellent anti-obesity effect compared to non-fermented samjung hwan.
실험예 2: 발효된 삼정환의 항비만효과 및 항고지혈 측정을 위한 동물실험Experimental Example 2: Animal experiment for the measurement of anti-obesity effect and antihyperlipidemia of fermented Samjeonghwan
도 3에서 나타난 바와 같이, 발효된 삼정환이 발효되지 않은 삼정환에 비해 지방세포 발현을 현저히 저해함을 알 수 있었다. 이에 발효된 삼정환이 실험동물에서 직접적으로 항비만 효과를 나타내는지 확인하는 실험을 하였고, 이러한 결과는 도 4에 나타나 있다.As shown in Figure 3, the fermented samjunghwan significantly inhibited the adipocyte expression compared to the fermented samjunghwan. The fermented Samjunghwan was tested to determine whether the anti-obesity effect in the experimental animals directly, these results are shown in FIG.
실험예 2-1 : 무게 및 먹이량 측정Experimental Example 2-1: Weight and Feeding Measurement
매 주 1회 실험동물의 무게와 먹이량을 측정하여 FER (Food efficiency ratio; body weight change(g) * 100/ total food intake(g) ) 값을 계산하였다.FER (Food efficiency ratio; body weight change (g) * 100 / total food intake (g)) was calculated by measuring the weight and the amount of foods once a week.
실험예 2-2: 비만 유발 및 약재 투여Experimental Example 2-2: Obesity Induction and Herbal Administration
흰 쥐를 각 군당 6마리로 나누어 (정상군, 비만유발군, 비만+삼정환군) 실험하였다. 정상군은 일반사료 (Nornal standard diet)를 비만유발군과 비만+삼정환군은 고지방사료 (High fat diet)를 공급하고 비만+삼정환군에는 삼정환을 매일 경구 투여하였다.White rats were divided into 6 rats in each group (normal group, obesity-inducing group, obesity + samjung-hwan group). The normal group fed normal diet (Normal standard diet) and the obese + Samjunghwan group fed a high fat diet, and the obese + Samjeonghwan group orally administered Samjunghwan daily.
실험예 2-3: 채혈 및 혈청분리Experimental Example 2-3: Blood Collection and Serum Separation
실험 시작 8주 후 각 군의 흰 쥐를 럼푼+졸레틸을 사용하여 마취시킨 후, 심장으로부터 혈액을 채취하여 혈액 항응고제인 Heparin이 첨가된 튜브에 담아 3000rpm에서 15분간 원심분리하여 혈청을 분리하여 냉동보관 하였다. After 8 weeks of experiment, white rats of each group were anesthetized using lump + zoletil, and blood was collected from the heart, and the blood was collected in a tube containing Heparin, a blood anticoagulant, and centrifuged at 3000 rpm for 15 minutes to separate serum and freeze it. Kept.
실험예 2-4: 혈청 중 각 성분함량 측정Experimental Example 2-4: measurement of each component content in serum
1) 혈중 총콜레스테롤 (Total cholesterol)1) Total cholesterol in blood
혈중 총콜레스테롤은 아산제약사의 총콜레스테롤 측정용시액 (T-CHO) kit를 이용하여 측정하였다. Serum 20㎕에 효소시약 3㎖을 잘 섞은 후, 5분간 37℃에서 incubation 시킨 다음 60분 이내에 흡광도 500nm에서 측정하였다.Total cholesterol in blood was measured using A-CHO T-CHO kit. After mixing 3 ml of enzyme reagent in 20 μl of Serum, the solution was incubated at 37 ° C. for 5 minutes and absorbed at 500 nm within 60 minutes.
2) 혈중 중성지방 (Triglyceride)2) Triglyceride
혈중 중성지방은 아산제약사의 중성지방 측정용시액 (Cleantech TG-S) kit를 이용하여 측정하였다. Serum 20㎕에 효소시약 3㎖을 잘 섞은 후, 10분간 37℃에서 incubation 시킨 다음 60분 이내에 흡광도 550nm에서 측정하였다.Blood triglycerides were measured using Asan Pharmaceutical's Triglyceride Test Kit (Cleantech TG-S). After mixing 3 ml of enzyme reagent in 20 μl of Serum, the solution was incubated at 37 ° C. for 10 minutes, and the absorbance was measured at 550 nm within 60 minutes.
3) 혈중 고밀도지단백 (High Density Lipiprotein : HDL-Cholesterol)3) High Density Lipiprotein (HDL-Cholesterol)
혈중 HDL은 아산제약사의 에취디엘 콜레스타제 측정용시액 (HDL-CHO) kit를 이용하여 측정하였다. Serum 200㎕에 효소시약 3㎖을 잘 섞은 후, 5분간 37℃에서 incubation 시킨 다음 60분 이내에 흡광도 500nm에서 측정하였다.Blood HDL was measured using Aesque Pharmaceutical's Ezediel Colletase Test Solution (HDL-CHO) kit. After mixing 3 ml of enzyme reagent in 200 μl of Serum, the solution was incubated at 37 ° C. for 5 minutes, and the absorbance was measured at 500 nm within 60 minutes.
4) 혈중 저밀도지단백 (Low Density Lipiprotein : LDL-Cholesterol)Low Density Lipiprotein (LDL-Cholesterol)
혈중 LDL은 총 콜레스테롤에서 중성지방과 고밀도지단백을 뺀 나머지를 이용하는 공식으로 측정하였다.Blood LDL was determined by the formula using total cholesterol minus triglyceride and high density lipoprotein.
실험예 2-5: 장기 무게 측정Experimental Example 2-5: Long-term weight measurement
채혈 직후 심장, 비장, 신장, 간장, 부고환지방, 복부내장지방 등의 무게를 측정하였다. 발효된 삼정환을 투입한 비만 유발군의 실험쥐가 발효 삼정환이 투입되지 않은 실험쥐에 비해 체중이 감소 되었고, 내장 지방의 중량 변화에도 영향을 주어 항비만 효과를 뒷받침 하였다.Immediately after blood collection, the weights of heart, spleen, kidney, liver, epididymal fat, and abdominal visceral fat were measured. Obesity-induced rats fed fermented Samjung-hwan lost weight compared to mice not fed fermented Samjung-hwan, and also affected the weight change of visceral fat to support the anti-obesity effect.
실험결과Experiment result
도 4a의 결과 각 군의 몸무게 증가를 먹은 양으로 나누어 주었을 때 삼정환을 먹인 군이 고지방 군에 비해 FER이 낮게 측정되었다.As a result of FIG. 4A, when the weight gain of each group was divided by the amount fed, the group fed Samjung-hwan was lower than the high fat group.
각 군의 내장지방, 간, 비장, 심장, 신장의 무게를 측정한 결과 삼정환을 투여한 군에서 복부지방이 현저하게 감소하였음을 확인하였다 (HFD : high fat diet, SJH : SamJeongHwan).As a result of measuring the weight of visceral fat, liver, spleen, heart and kidney of each group, it was confirmed that abdominal fat was significantly decreased in the Samjung-hwan group (HFD: high fat diet, SJH: SamJeongHwan).
이상의 결과는 발효된 삼정환이 항비만, 대사개선 효과가 있음을 시사하여 본 실험의 수행을 위한 근거를 마련하였다. 특히 체중보다 복부지방 위주의 감량과 중성지방, 저밀도지단백콜레스테롤의 감소 및 고밀도지단백콜레스테롤의 증가가 두드러진 것은 단순체중과다 보다 복부비만에 더 효과가 분명하여 인슐린 저항성 및 고지혈증 등 대사증후군의 치료제로서 역할을 기대할 수 있었다.The above results suggested that fermented Samjunghwan had anti-obesity and metabolic improvement effects, thus providing a basis for the performance of this experiment. In particular, weight loss, weight loss, triglyceride, low density lipoprotein cholesterol, and high density lipoprotein cholesterol were more pronounced than body weight, which is more effective for abdominal obesity than overweight, thus acting as a treatment for metabolic syndrome such as insulin resistance and hyperlipidemia. I could expect.
실험예 3: 발효된 삼정환의 우점종 미생물의 동정Experimental Example 3: Identification of Dominant Microorganisms of Fermented Samjeonghwan
도 3과 도 4의 결과, 발효된 삼정환의 항비만 효과를 확인할 수 있었다. 본 실험예3에서는 이러한 발효된 삼정환의 항비만 효과에 영향을 미치는 우점종 미생물을 동정하였다.As a result of Figures 3 and 4, it was confirmed that the anti-obesity effect of fermented Samjeonghwan. In Experimental Example 3, dominant species microorganisms affecting the anti-obesity effect of the fermented Samjeonghwan were identified.
실험예 3-1: 평판배지법을 이용한 미생물 동정Experimental Example 3-1: Identification of Microorganisms Using the Plate Medium Method
1) 유산균 이외의 미생물 분석1) Analysis of microorganisms other than lactic acid bacteria
본 발명의 유산균 이외의 미생물 분석은 2008 식품공전, 건강기능식품공전, 대한약전에 준하여 실시된 것으로, 멸균된 혐기수 9ml 에 발효 한약재 삼정환 분말 1g을 희석하여 검액을 제조하였다.Microorganism analysis other than lactic acid bacteria of the present invention was carried out in accordance with the 2008 Food Code, Health Functional Food Code, Korea Pharmacopoeia, was prepared by diluting 1g of fermented herbal medicine Samjunghwan powder in 9ml of sterilized anaerobic water.
일반세균의 경우, 오염검출배지로는 Plate Count Agar (PCA), Trypic Soy Agar (TSA), Nutrient Agat (NA), Blood Plate Agar (BAP), SBM, KF을 사용하여 37℃, 48시간, 호기배양 (SBM의 경우, 42℃)을 하였고, 진균류의 경우, 오염검출배지로는 DRBC Agar, Potato Dextrose Agar (PDA)을 사용하여 25℃, 5일, 호기배양에서 배양하였고, 대장균군의 경우 오염검출배지로는 DLA, EMB을 사용하여 37℃, 72시간, 호기배양하였으며 , 병원성균의 경우 오염검출배지로는 Oxford agar, MYP, Macconky agar, MSA을 사용하였으며 Oxford agar, MYP는 30℃, 24시간을, Macconky agar는 35℃, 24시간을, MSA는 37℃, 16~24시간을 배양하였다.In the case of general bacteria, the contamination detection medium was 37 ° C. for 48 hours using Plate Count Agar (PCA), Trypic Soy Agar (TSA), Nutrient Agat (NA), Blood Plate Agar (BAP), SBM, and KF. Cultures (42 ° C for SBM) and fungi were cultured in aerobic culture at 25 ° C for 5 days using DRBC Agar and Potato Dextrose Agar (PDA) as contamination detection media. For detection of pathogens, Oxford agar, MYP, Macconky agar, and MSA were used for the detection of pathogenic bacteria. Time, Macconky agar was incubated at 35 ℃, 24 hours, MSA 37 ℃, 16-24 hours.
표 2 일반세균 분석 결과
TABLE 2 General bacteria analysis result
시료 | 항목 | 배양 배지 | 오염도 | 비고 |
삼정환 | 일반세균 | PCA | 5.00E+06 | |
TSA | 4.20E+05 | |||
NA | 6.50E+05 | |||
BAP | 1.50E+06 | |||
SBM | 1.80E+05 | |||
KF | - | |||
진균류 | DRBC | 10 colony | ||
PDA | TNTC대장균군 | |||
DLA | - | |||
EMB | 3.50E+05 |
sample | Item | Culture medium | Pollution | Remarks |
Sam Jung Hwan | General bacteria | PCA | 5.00E + 06 | |
TSA | 4.20E + 05 | |||
NA | 6.50E + 05 | |||
BAP | 1.50E + 06 | |||
SBM | 1.80E + 05 | |||
KF | - | |||
| DRBC | 10 colony | ||
PDA | TNTC coliform group | |||
DLA | - | |||
EMB | 3.50E + 05 |
표 3 병원성 미생물 분석 결과
TABLE 3 Pathogenic Microorganism Assay
시료 | 항목 | 배양 배지 | colony 수 | 의심 colony 수 | 비고 |
삼정환 | Listeria | Oxford | 2.40E+03 | 1.10E+03 | |
B.cereus | MYP | 6.00E+04 | - | ||
Salmonella | Macconky | - | - | ||
S.aureus | MSA | 2.40E+03 | - |
sample | Item | Culture medium | colony can | Suspected colony | Remarks |
Sam Jung Hwan | Listeria | Oxford | 2.40E + 03 | 1.10E + 03 | |
B.cereus | MYP | 6.00E + 04 | - | ||
Salmonella | Macconky | - | - | ||
S.aureus | MSA | 2.40E + 03 | - |
상기 표 2 및 표 3에서 나타난 바와 같이, 자연발효된 삼정환에는 유산균외에 대장균군, 진균류 및 각종 미생물이 공존하고 있음을 확인할 수 있었다.As shown in Table 2 and Table 3, it was confirmed that E. coli, fungi, and various microorganisms coexist in lactic acid bacteria in naturally fermented Samjeonghwan.
2) 유산균 분석 (건강기능식품 준하여 실시)2) Lactobacillus analysis (conducted in accordance with health functional food)
멸균된 혐기수 9 ml에 발효 한약재 삼정환 분말 1g을 희석하고 20분간 용출하고, 10진 희석법을 이용하여 희석한 후, 10-3~10-10 희석한 검액 1ml를 petridish에 분주하고 배양배지인 MRS 및 BL agar를 분주하였다. 이후, 각 petri dish를 37℃, 48~72hr 배양한 후, colony 수를 계측하였다.After diluting 1 g of fermented medicinal herb Samjunghwan powder in 9 ml of sterilized anaerobic water and eluting for 20 minutes, diluting using 10-degree dilution method, 1 ml of 10-3 ~ 10-10 diluted sample solution was dispensed into petridish. MRS and BL agar were dispensed. Thereafter, each petri dish was incubated at 37 ° C. for 48 ~ 72hr, and the colony number was measured.
표 4 유산균수 분석 결과
Table 4 Lactobacillus Count Analysis Results
시료 | 항목 | 배양 배지 | 미생물 수 |
삼정환 | 생균수 | MRS | 점질물 형성 |
BL | 7.80E+05 |
sample | Item | Culture medium | Microbial count |
Sam Jung Hwan | Viable count | MRS | Viscous Formation |
BL | 7.80E + 05 |
상기 표 4에 나타난 바와 같이, MRS agar는 점질물이 형성되어 colony 수를 계측하지 못 하였고, BL 배지에서 형성된 colony를 BCP를 첨가한 BL agar에 접종하여 혐기 및 호기 조건에서 동시에 배양한 결과, 대부분의 colony가 Bifidobacterium으로 확인되었다. 하기 도 5 및 도 6에는 각 배지별 미생물 검출사진과 현미경 검경사진이 나타나 있다.As shown in Table 4, MRS agar was a viscous material was formed, the colony number could not be measured, the colony formed in BL medium was inoculated in BL agar added with BCP incubated simultaneously in anaerobic and aerobic conditions, most of the results Colony was identified as Bifidobacterium. 5 and 6 show microbial micrographs and microscopic images of the respective media.
실험예 3-2: PCR을 이용한 미생물 동정Experimental Example 3-2: Identification of Microorganisms Using PCR
각 균주의 Standard graph와 비교하여 균수를 측정하였는데, 각 균주에 대한 Standard graph는 각 균주를 배양하여 1 mL에 존재하는 균수를 측정한 후 1 mL에 존재하는 균주를 이용하여 DNA를 추출하였으며, 십배희석법에 의해 희석하여 SYBR Green I을 이용한 Real-time PCR을 진행하고 graph를 작성하여 data로써 이용하였다. 삼정환 분말 0.1g을 Lysozyme에 풀어준 후 DNA preparation kit를 이용해 DNA 추출하였다.The number of bacteria was measured by comparing with the standard graph of each strain.The standard graph for each strain was cultured for each strain to measure the number of bacteria present in 1 mL, and DNA was extracted using the strain present in 1 mL. After dilution by dilution method, real-time PCR using SYBR Green I was performed, and a graph was used as data. 0.1g Samjunghwan powder was dissolved in Lysozyme, and DNA was extracted using a DNA preparation kit.
하기 표 5, 표 6, 표 7 에는 PCR조건 및 Bifidobacterium longum, Bifidobacterim bifidum, Bifidobacterium breve, Lactobacillus acidophilus, Escherichia coli, Salmonella spp., Candida albicans, Bacteroides fragilis 의 8개의 균주에 대한 프라이머를 나타내었고, 표 8 및 도 7에서는 삼정환 분말에 존재하는 각 균주의 존재량을 나타내었다.Table 5, Table 6, Table 7 shows the PCR conditions and primers for eight strains of Bifidobacterium longum, Bifidobacterim bifidum, Bifidobacterium breve, Lactobacillus acidophilus, Escherichia coli, Salmonella spp., Candida albicans, Bacteroides fragilis, Table 8 And Figure 7 shows the amount of each strain present in the Samjunghwan powder.
표 5 Real Time PCR 조성
Table 5 Real Time PCR Composition
구분 | 용량 | 비고 | |
DNA | 1 λ | ||
Mixture | 10 λ | ||
Primer | F | 0.5 λ | R |
D.W | 0.5 λ | ||
Total | 8 λ | ||
20 λ | per well |
division | Volume | Remarks | |
| 1 | ||
Mixture | |||
10 λ | |||
Primer | F | 0.5 λ | R |
DW | 0.5 λ | ||
Total | 8 | ||
20 λ | per well |
표 6 Real Time PCR Operation
Table 6 Real Time PCR Operation
구분 | 온도(℃) | 시간 | 비고 |
Pre-heating | 95 | 4 min | Amplification |
95 | 15 sec | 55 times | |
50 | 15 sec | ||
72 | 20 secMelting | ||
95 | 1 sec | ||
50 | 1 sec | ||
90 | 30 sec | Cooling | |
40 | continuous |
division | Temperature (℃) | time | Remarks | |
Pre-heating | 95 | 4 min | Amplification | |
95 | 15 sec | 55 | ||
50 | 15 sec | |||
72 | 20 secMelting | |||
95 | 1 | |||
50 | 1 sec | |||
90 | 30 | Cooling | ||
40 | continuous |
표 7 Strain-specific primer
TABLE 7 Strain-specific primer
Strain | Amplicon size | Primer(5’→3’)Bifidobacterium bifidum278 bp | |
F | CCA CAT GAT CGC ATG TGA TTG | ||
288 bp | R | CCG AAG GCT TGC TCC CAA ABifidobacterium breve | |
Bifidobacterium longum | F | CCG GAT GCT CCA TCA CAC | |
106 bp | R | ACA AAG TGC CTT GCT CCC T | |
Lactobacillus acidophilus | F | CAG TTG ATC GCA TGG TCT T | |
85 bp | R | TAC CCG TCG AAG CCA C | |
Escherichia coli | F | GAA AGA GCC CAA ACC AAG TGA TT | |
340 bp | R | CTT CCC AGA TAA TTC AAC TAT CGC TTA | |
Candida albicans | F | GTT AAT ACC TTT GCT CAT TGA | |
140 bp | R | ACC AGG GTA TCT AAT CCT GTT | |
F | CTC GTA GTT GAA CCT TGG | ||
152 bp | R | GCC TGC TTT GAA CAC TCTSalmonella spp. | |
F | TAC CAA AGC TAA ACG CGC AGC T | ||
R | TGA TCA GGA AAT CTT CCA GTT GCBacteroides fragilis176 bp | ||
F | GAA AGC ATT AAG TAT TCC ACC TG | ||
R | CGG TGA TTG GTC ACT GAC A |
Strain | Amplicon size | Primer (5 '→ 3') Bifidobacterium bifidum 278 bp | |
F | CCA CAT GAT CGC ATG TGA TTG | ||
288 bp | R | CCG AAG GCT TGC TCC CAA A Bifidobacterium breve | |
Bifidobacterium longum | F | CCG GAT GCT CCA TCA CAC | |
106 bp | R | ACA AAG TGC CTT GCT CCC T | |
Lactobacillus acidophilus | F | CAG TTG ATC GCA TGG TCT T | |
85 bp | R | TAC CCG TCG AAG CCA C | |
Escherichia coli | F | GAA AGA GCC CAA ACC AAG TGA TT | |
340 bp | R | CTT CCC AGA TAA TTC AAC TAT CGC TTA | |
Candida albicans | F | GTT AAT ACC TTT | |
140 bp | R | ACC AGG GTA TCT AAT CCT GTT | |
F | CTC GTA GTT GAA CCT TGG | ||
152 bp | R | GCC TGC TTT GAA CAC TCTS almonella spp. | |
F | TAC CAA AGC TAA ACG CGC AGC T | ||
R | TGA TCA GGA AAT CTT CCA GTT GC Bacteroides fragilis 176 bp | ||
F | GAA AGC ATT AAG TAT TCC ACC TG | ||
R | CGG TGA TTG GTC ACT GAC A |
표 8 삼정환 분말에 존재하는 각 균주의 존재량
Table 8 Amount of each strain present in Samjunghwan powder
구 분 | 삼정환 분말에 존재하는 양 |
Bifidobacterium longum | 2.10E+04 |
Lactobacillus acidophilus | 3.00E+05 |
Bifidobacterium bifidum | 4.00E+04 |
Bifidobacterium breve | 1.10E+03 |
Escherichia coli | 6.00E+02 |
Salmonella spp. | 1.30E+02 |
Candida albicans | 4.60E+06 |
Bacteroides fragilis | 5.00E+01 |
division | Amount present in Samjunghwan Powder |
Bifidobacterium longum | 2.10E + 04 |
Lactobacillus acidophilus | 3.00E + 05 |
Bifidobacterium bifidum | 4.00E + 04 |
Bifidobacterium breve | 1.10E + 03 |
Escherichia coli | 6.00E + 02 |
Salmonella spp. | 1.30E + 02 |
Candida albicans | 4.60E + 06 |
Bacteroides fragilis | 5.00E + 01 |
기존에 측정해 놓은 standard curve를 이용하여 CP값을 균수로 변환하였다.CP value was converted to the number of bacteria using the standard curve measured previously.
표 8과 도 7에 나타난 바와 같이, 유산균주 중에 Bifidobacterium longum과 Bifidobacterium breve가 기준치 이상의 우점을 나타냄을 확인할 수 있었다. As shown in Table 8 and Figure 7, it was confirmed that Bifidobacterium longum and Bifidobacterium breve in the lactic acid bacteria showed a predominance above the reference value.
실험예 4: 다양한 균주에 의해 발효된 삼정환의 발효 특성Experimental Example 4: Fermentation Characteristics of Samjeonghwan Fermented by Various Strains
본 실험예에서는 발효 삼정환이 발효되지 않은 삼정환에 비해 항비만 효과가 우수함을 증명한 상기 실험예들을 바탕으로, 발효 미생물 이외의 균들이 혼합되지 않은 발효 삼정환에서 발효효능이 가장 큰 미생물을 찾고자 하였다.In this Experimental Example, based on the above experiments proved that the fermentation Samjeonghwan anti-obesity effect is superior to the non-fermented Samjeonghwan, to find the microorganism with the highest fermentation efficacy in the fermentation Samjeonghwan not mixed with the fermentation microorganism It was.
발효 균주는 MRS broth에 계대 배양한 김치로부터 분리한 Lactobacillus plantarum P23과 YM broth에 계대 배양한 맥주 발효 균주인 Yeast DSII를 각각 총 volume의 1% (100ml)씩 제조한 삼정환에 접종하였다. 복발효의 경우 각 균주를 0.5% (50ml)씩 접종하였다. 접종 후 각 옹기를 직사광선을 피하는 음지에 두어 발효 시켰다. 기간은 2008. 07.24 ~ 09.06 발효하였으며, 각 균주가 성장하는 시간에 맞추어 1주간 3회의 sampling을 실시하였고 그 후로는 주당 1회 sampling을 하여, 자연 상태 발효, 유산균 발효, 효모 발효, 유산균과 효모를 동시에 접종하는 형태의 복발효 4종의 pH 변화 및 환원당의 변화를 통해 이들 간의 발효 정도를 확인하였는데, 이는 도 8, 도 9 및 도 10에 나타나 있다.The fermentation strains were inoculated into Lactobacillus plantarum P23 isolated from kimchi passaged on MRS broth and Yeast DSII, a beer fermentation strain passaged on YM broth, in 1% (100ml) of the total volume. In the case of double fermentation, each strain was inoculated with 0.5% (50ml). After inoculation, each onggi was fermented in a shade avoiding direct sunlight. The fermentation period was 2008. 07.24 ~ 09.06, and three samplings per week were carried out in accordance with the growth time of each strain. Thereafter, sampling was performed once per week, followed by natural fermentation, lactic acid bacteria fermentation, yeast fermentation, lactic acid bacteria and yeast. The fermentation degree was confirmed by changing the pH and reducing sugars of the four fermentations in the form of inoculation at the same time, which are shown in FIGS. 8, 9 and 10.
도 8 및 도 9에 나타난 바와 같이, 유산균 발효된 삼정환, 복발효된 삼정환, 효모 발효된 삼정환, 자연발효된 삼정환 순으로 pH 감소가 빠르게 진행되는 것으로 보아 상기 유산균 발효, 복발효, 효모발효는 자연발효에 비해 발효효과가 우수함을 확인할 수 있었다. 또한, 실험예 1에서 확인한 바와 같이, 자연발효된 삼정환이 발효되지 않은 삼정환에 비해 항비만 효과가 우수하였기에 상기 유산균 발효된 삼정환, 복발효된 삼정환, 효모 발효된 삼정환도 발효되지 않은 삼정환에 비해 항비만 효과가 우수함을 알수 있다.As shown in Figure 8 and 9, the lactic acid bacteria fermented, fermented, fermented, fermented, fermented, fermented, fermented, fermented, fermented, fermented, fermented, fermented, fermented, fermented, Yeast fermentation was confirmed that the fermentation effect is superior to natural fermentation. In addition, as confirmed in Experimental Example 1, the fermented Samjeong hwan, fermented Samjeong hwan, yeast fermented Samjeong hwan were not fermented because the fermented samjeong hwan was more effective than the fermented Samjeong hwan. It can be seen that the anti-obesity effect is superior to the ring.
도 10에서 나타난 바와 같이, 유산균 발효된 삼정환이 가장 빠른 발효가 이루어져 1주내에 발효가 원활이 이루어지고 2주차에 거의 모든 환원당이 소모되는 것을 확인할 수 있으며, 복발효된 삼정환과 효모 발효된 삼정환이 거의 비슷한 속도로 당을 소모하는 패턴을 보이며, 자연발효된 삼정환이 2주에까지 당의 소모를 거의 안하다가 3주차에 급격한 당의 소모를 하며 발효가 진행되는 것을 확인하였다. As shown in FIG. 10, the fastest fermentation of the lactic acid bacterium fermented Samjung-hwan is performed smoothly within one week and almost all reducing sugars are consumed in the second week, and the fermented Samjeong-hwan and yeast fermented Samjeong-hwan are It showed a pattern of consuming sugar at about the same speed, and fermentation proceeded rapidly after 3 weeks of rapid consumption of sugar.
따라서 실험예 1에서 확인한 바와 같이, 자연발효된 삼정환이 발효되지 않은 삼정환에 비해 항비만 효과가 우수하였기에 상기 유산균 발효된 삼정환, 복발효된 삼정환, 효모 발효된 삼정환도 발효되지 않은 삼정환에 비해 항비만 효과가 우수함을 알 수 있으며, 이 중 유산균 발효된 삼정환이 가장 단시간 내에 좋은 발효 효과를 보이는 것으로 보아 항비만 효과도 우수함을 알 수 있다. Therefore, as confirmed in Experimental Example 1, the fermented Samjeong hwan, fermented Samjeong hwan, yeast fermented Samjeong hwan were not fermented because the fermented samjeong hwan was more effective than the fermented Samjeong hwan. It can be seen that the anti-obesity effect is superior to that, among which the lactic acid bacteria fermented Samjung-hwan shows a good fermentation effect within the shortest time, and thus the anti-obesity effect is also excellent.
실험예 5: 유산균을 이용한 삼정환 약재의 발효Experimental Example 5: Fermentation of Samjunghwan Herb Using Lactic Acid Bacteria
여러 가지 유산균주 중 건강기능개선 효능 (면역조절 기능, 콜레스테롤 저하 기능, 정장 효능)이 검증된 몇 종을 우선적으로 선택하고 삼정환 약재를 이용하여 유산균에 의한 한약재 발효 가능성을 확인하였다.Among several lactobacillus strains, several health-improving effects (immune control function, cholesterol lowering function, intestinal efficacy) were selected first, and the possibility of fermentation of herbal medicine by lactic acid bacteria was confirmed using Samjunghwan medicinal herbs.
실험예 5-1: 실험 방법Experimental Example 5-1: Experimental Method
발효에 사용한 균주는 Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus plantarum P23, Enterococcus faecium, Pediococcus pentosaceus 로서 L. plantarum P23과 P. pentosaceus는 김치에서 분리된 식물성 유산균이다. 한방발효 배지는 삼정환 제조법대로 오디, 창출, 및 지골피를 각각 20: 1: 1의 비율로 섞어 준비하였다. 최종 pH는 NaOH를 사용하여 pH=6.5로 보정하였다. 유산균 종균은 약 107 cfu/ml (1%)의 농도로 각 플라스크 접종한 후 37℃에서 최장 61 시간까지 정치 배양 하였다. 발효 중간 및 발효 후의 발효액 일부는 원심분리를 통해 유산균을 제거하고 상등액을 이용하여 시간별 pH 변화를 측정하였다. 또한 발효전후의 상등액을 HPLC를 이용하여 크로마토그램의 변화를 분석하였다.The strains used for fermentation are Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus plantarum P23, Enterococcus faecium, Pediococcus pentosaceus. L. plantarum P23 and P. pentosaceus are plant lactic acid bacteria isolated from Kimchi. Herbal fermentation medium was prepared by mixing the audio, creation, and phalanges in a ratio of 20: 1: 1 according to the Samjunghwan manufacturing method. Final pH was corrected to pH = 6.5 using NaOH. Lactobacillus spawn was incubated at a concentration of about 10 7 cfu / ml (1%) and incubated at 37 ° C. for up to 61 hours. Some of the fermentation broth in the middle of fermentation and after fermentation were removed by lactic acid bacteria through centrifugation, and pH change was measured over time using supernatant. In addition, the supernatant before and after fermentation was analyzed for chromatogram change using HPLC.
실험예 5-2 : 실험 결과Experimental Example 5-2: Experimental Results
동일량의 유산균을 접종하여 발효 전, 발효 후 23시간 및 61 시간의 pH를 분석한 결과 L. plantarum P23으로 배양한 발효액에서 가장 큰 pH 변화가 관찰되었다 (표 9). 이 결과는 L. plantarum P23이 삼정환 약재를 이용하여 가장 왕성하게 생장함을 의미한다.As a result of inoculating the same amount of lactic acid bacteria, pH of 23 hours and 61 hours before and after fermentation was analyzed, the largest pH change was observed in the fermentation broth cultured with L. plantarum P23 (Table 9). This result suggests that L. plantarum P23 grows most actively with Samjunghwan.
표 9 발효시간 대별 pH 변화
Table 9 PH change by fermentation time
발효 시간 | ||
유산균 | 24 시간 | 60 시간 |
B. longum | 4.31 | 4.32 |
E. faecium | 4.65 | 4.35 |
L. acidophilus | 4.45 | 3.93 |
L. plantarum P23 | 4.05 | 3.98 |
P. pentosaceus | 4.25 | 4.18 |
Fermentation time | ||
Lactobacillus | 24 | 60 hours |
B. longum | 4.31 | 4.32 |
E. faecium | 4.65 | 4.35 |
L. acidophilus | 4.45 | 3.93 |
L. plantarum P23 | 4.05 | 3.98 |
P. pentosaceus | 4.25 | 4.18 |
UV 254 nm에서 유산균을 접종하지 않은 대조군과 비교하여 1% 유산균 접종 후 peak의 패턴이 변화 양상을 분석한 결과 L. plantarum P23, L. acidophilus, P. pentosaceus, E. faecium, B. longum 순으로 peak 변화가 많이 관찰되었으며 (도 11, 12 및 13) L. plantarum P23및 L. acidophilus을 접종한 경우 peak 변화가 유사하며, 각 구간별로 상이한 패턴이 관찰되었다.As a result of analyzing the pattern of peak after 1% lactic acid inoculation compared to the control group not inoculated with lactic acid bacteria at UV 254 nm, L. plantarum P23, L. acidophilus, P. pentosaceus, E. faecium, and B. longum A lot of peak changes were observed (FIGS. 11, 12, and 13). When inoculated with L. plantarum P23 and L. acidophilus, the peak changes were similar, and different patterns were observed for each section.
UV 280 nm에서 L. plantarum P23또는 L. acidophilus에 의한 발효액을 분석한 결과, 비슷한 RT값에서 peak가 감소하고 증가하는 구간이 존재하며, 증가한 구간을 추정하건데 유산균 접종 시 배양여액에 존재하는 단백질 계열의 물질이 포함되어 유산균을 접종하지 않은 대조군 보다 높게 나왔을 것으로 사료되며, 반대로 감소한 구간에서는 유산균에 의해 단백질 계열의 물질이 소모되었을 것으로 추정된다.As a result of analyzing fermentation broth by L. plantarum P23 or L. acidophilus at UV 280 nm, there is a section where the peak decreases and increases at a similar RT value. It is believed that the lactic acid bacteria were consumed higher than the control group without the inoculation of lactic acid bacteria.
**
실험예 6: 다양한 유산균주에 의해 발효된 삼정환의 지방세포 분화 억제능 Experimental Example 6: Inhibition of Adipocyte Differentiation of Samjeonghwan Fermented by Various Lactic Acid Strains
Lactobacillus acidophilus, L. plantarum P23, Pediococcus pentosaceus, Bifidobacterium longum, Enterococcus faecium 등 5종의 유산균으로 삼정환에 접종하여 전지방세포에서 지방세포로의 분화 억제능을 현미경으로 관찰하였다. 삼정환은 상심자를 갈아 즙으로 낸 후 창출과 지골피 분말을 섞어 만들고 유산균주 접종 직전에 오토클레이브로 멸균시켰다.Lactobacillus acidophilus, L. plantarum P23, Pediococcus pentosaceus, Bifidobacterium longum, Enterococcus faecium were inoculated into Samjunghwan and observed the microscopic inhibition of differentiation from fat cells to adipocytes. Samjunghwan was ground juice of juice, mixed with creation and phalanges, and sterilized by autoclave immediately before inoculation of lactic acid strain.
분화 실험에서 L. plantarum P23을 사용하여 발효시킨 삼정환에서 가장 뛰어난 지방세포 분화억제능력이 관찰되었다. In the differentiation experiment, the best fat cell differentiation inhibitory ability was observed in Samjunghwan fermented with L. plantarum P23.
실험예 7: Experimental Example 7:
L. plantarum L. plantarum
P23P23
의 콜레스테롤 저하 효능Cholesterol Lowering Efficacy
유산균의 일종인 L. plantarum P23의 콜레스테롤 저하효능을 동물모델을 통해 확인하였다 (Jeun 등. 2010. Hypocholesterolemic effects of Lactobacillus plantarum KCTC 3928 by increased bile acid excretion in C57BL/6 mice. Nutrition. 26, 321). 이 연구결과에서 L. plantarum P23생균을 섭취한 그룹은 대조군과 비교하여 low density lipoprotein (LDL), triacylglyceride 등의 수준이 현저히 감소하는 것으로 나타났으며 (도 15와 표 10), 간에서 콜레스테롤 분해를 촉진하여 분변으로 배출되게 함으로써 혈중 콜레스테롤 수치를 낮추는 것으로 보고하였다. The cholesterol lowering effect of L. plantarum P23, a type of lactic acid bacterium, was confirmed by an animal model (Jeun et al. 2010. Hypocholesterolemic effects of Lactobacillus plantarum KCTC 3928 by increased bile acid excretion in C57BL / 6 mice. Nutrition. 26, 321). In this study, L. plantarum P23 bacteria were found to significantly reduce the levels of low density lipoprotein (LDL), triacylglyceride, etc. compared to the control group (Fig. 15 and Table 10). It has been reported to lower blood cholesterol levels by facilitating excretion into feces.
이처럼 L. plantarum P23은 혈장내 지질의 분포를 개선하는 효과가 있는 것으로 나타났다. 즉, 혈장 내 총 cholesterol 및 LDL 농도를 유의적으로 낮추는 효능을 가지고 있기 때문에 고지혈증 개선에 기여할 것이다.Thus L. plantarum P23 has been shown to improve the distribution of lipids in the plasma. That is, since it has the effect of significantly lowering the total cholesterol and LDL concentration in plasma will contribute to the improvement of hyperlipidemia.
본 발명의 상기 발효물을 함유하는 약학조성물의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.The preparation example of the pharmaceutical composition containing the fermentation product of the present invention will be described, but the present invention is not intended to limit the present invention but is only intended to be described in detail.
제제예 1. 산제의 제조Formulation Example 1 Preparation of Powder
상기 발효물 20 mg20 mg of the fermented product
유당 100 mg Lactose 100 mg
탈크 10 mg Talc 10 mg
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조한다.The above ingredients are mixed and filled in an airtight cloth to prepare a powder.
제제예 2. 정제의 제조Formulation Example 2 Preparation of Tablet
상기 발효물 10 mg10 mg of the fermented product
옥수수전분 100 mg Corn starch 100 mg
유당 100 mg Lactose 100 mg
스테아린산 마그네슘 2 mg2 mg magnesium stearate
상기의 성분들을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.After mixing the above components, tablets are prepared by tableting according to a conventional method for preparing tablets.
제제예 3. 캅셀제의 제조Formulation Example 3 Preparation of Capsule
상기 발효물 10 mg10 mg of the fermented product
결정성 셀룰로오스 3 mg3 mg of crystalline cellulose
락토오스 14.8 mgLactose 14.8 mg
마그네슘 스테아레이트 0.2 mgMagnesium Stearate 0.2 mg
통상의 캡슐제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충전하여 캡슐제를 제조한다.According to a conventional capsule preparation method, the above ingredients are mixed and filled into gelatin capsules to prepare capsules.
제제예 4. 주사제의 제조Formulation Example 4 Preparation of Injection
상기 발효물 10 mg10 mg of the fermented product
만니톨 180 mgMannitol 180 mg
주사용 멸균 증류수 2974 mgSterile distilled water for injection 2974 mg
Na2HPO4·12H2O 26 mgNa2HPO412H2O 26 mg
통상의 주사제의 제조방법에 따라 1 앰플당 (2 ㎖) 상기의 성분 함량으로 제조한다.According to the conventional method for preparing an injection, the amount of the above ingredient is prepared per ampoule (2 ml).
제제예 5. 액제의 제조Formulation Example 5 Preparation of Liquid
상기 발효물 20 mg20 mg of the fermented product
이성화당 10 g10 g of isomerized sugar
만니톨 5 g5 g of mannitol
정제수 적량Purified water
통상의 액제의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고 레몬향을 적량 가한 다음 상기의 성분을 혼합한 다음 정제수를 가하여 전체를 정제수를 가하여 전체 100㎖로 조절한 후 갈색병에 충진하여 멸균시켜 액제를 제조한다.According to the conventional method of preparing a liquid solution, each component is added to the purified water to dissolve, the lemon flavor is appropriately added, the above components are mixed, purified water is added, the whole is purified to 100 ml, and then filled in a brown bottle. The solution is prepared by sterilization.
제제예 6. 건강식품의 제조Formulation Example 6 Preparation of Health Food
상기 발효물 1000 ㎎1000 mg of the fermented product
비타민 혼합물 적량Vitamin mixture proper amount
비타민 A 아세테이트 70 ㎍70 μg of Vitamin A Acetate
비타민 E 1.0 ㎎Vitamin E 1.0 mg
비타민 B1 0.13 ㎎Vitamin B1 0.13 mg
비타민 B2 0.15 ㎎Vitamin B2 0.15 mg
비타민 B6 0.5 ㎎Vitamin B6 0.5 mg
비타민 B12 0.2 ㎍0.2 μg of vitamin B12
비타민 C 10 ㎎ Vitamin C 10 mg
비오틴 10 ㎍10 μg biotin
니코틴산아미드 1.7 ㎎Nicotinic Acid 1.7 mg
엽산 50 ㎍ Folate 50 ㎍
판토텐산 칼슘 0.5 ㎎Calcium Pantothenate 0.5mg
무기질 혼합물 적량Mineral mixture
황산제1철 1.75 ㎎Ferrous Sulfate 1.75 mg
산화아연 0.82 ㎎Zinc Oxide 0.82 mg
탄산마그네슘 25.3 ㎎Magnesium carbonate 25.3 mg
제1인산칼륨 15 ㎎Potassium monophosphate 15 mg
제2인산칼슘 55 ㎎Dibasic calcium phosphate 55 mg
구연산칼륨 90 ㎎Potassium Citrate 90 mg
탄산칼슘 100 ㎎ Calcium Carbonate 100 mg
염화마그네슘 24.8 ㎎Magnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강식품 조성물 제조에 사용할 수 있다.Although the composition ratio of the vitamin and mineral mixture is a composition suitable for a relatively healthy food in a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method. The granules may be prepared and used for preparing a health food composition according to a conventional method.
제제예 7. 건강음료의 제조Formulation Example 7 Preparation of Health Beverage
상기 발효물 100 ㎎100 mg of the fermented product
비타민 C 15 g15 g of vitamin C
비타민 E(분말) 100 g100 g of vitamin E (powder)
젖산철 19.75 gIron lactate 19.75 g
산화아연 3.5 g3.5 g of zinc oxide
니코틴산아미드 3.5 gNicotinamide 3.5 g
비타민 A 0.2 g0.2 g of vitamin A
비타민 B1 0.25 g0.25 g of vitamin B1
비타민 B2 0.3g0.3 g of vitamin B2
물 정량Water quantification
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간 동안 85 ℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2 ℓ 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강음료 조성물 제조에 사용한다.After mixing the above components in accordance with the conventional healthy beverage preparation method, and stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilization and refrigerated Used to prepare the healthy beverage composition of the invention.
상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만 수요계층이나, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.Although the composition ratio is mixed with a component suitable for a favorite beverage in a preferred embodiment, the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.
본 발명의 창출, 지골피, 상심자를 포함하는 발효물을 유효성분으로 함유하는 조성물은 비만 및 고지혈증의 예방 및 치료용 의약품 또는 건강식품으로 활용이 가능하다.The composition containing the fermentation product including the creation of the present invention, phalanges, lettuce, as an active ingredient can be used as a pharmaceutical or health food for the prevention and treatment of obesity and hyperlipidemia.
Claims (10)
- 지골피, 창출, 상심자를 포함하는 한약재의 발효물 또는 발효물의 추출물을 유효성분으로 함유하는 비만 또는 고지혈증의 예방 및 치료용 건강 기능식품. Health functional food for the prevention and treatment of obesity or hyperlipidemia, containing the fermentation product of herbal medicine or extract of the fermentation product including phalanges, creation, loser.
- 제 1항에 있어서,The method of claim 1,상기 건강식품은 건강음료인 것을 특징으로 하는 건강 기능식품. The health food is a health functional food, characterized in that the health drink.
- 지골피, 창출, 상심자를 포함하는 한약재의 발효물 또는 발효물의 추출물을 유효성분으로 함유하는 비만 또는 고지혈증의 예방 및 치료용 조성물. Phosphorus, creation, a composition for the prevention and treatment of obesity or hyperlipidemia, which contains fermented products of herbal medicine or extracts of fermented products, including the loser as an active ingredient.
- 제 3항에 있어서, 상기 추출물은 물, 탄소수 1 내지 4의 저급 알코올 또는 이들의 혼합용매로 추출된 것을 특징으로 하는 조성물.The composition of claim 3, wherein the extract is extracted with water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.
- 제 3항에 있어서, 상기 창출의 중량부를 10으로 둘 경우, 지골피의 중량부는 8 내지 12, 상심자의 중량부는 18 내지 22인 것을 특징으로 하는 조성물.4. The composition according to claim 3, wherein when the weight part of the creation is set to 10, the weight part of the phalanges is 8 to 12, and the weight part of the heart beater is 18 to 22.
- 제 3항에 있어서, The method of claim 3, wherein상기 발효물은 비피도박테리움 롱검(Bifidobacterium longum)과 비피오박테리움 브레브(Bifidobacterium breve)로 이루어진 군으로부터 선택된 미생물에 의해 발효된 것을 특징으로 하는 조성물.The fermentation product is characterized in that the fermented by a microorganism selected from the group consisting of Bifidobacterium longum and Bifidobacterium breve.
- 제 3항에 있어서, The method of claim 3, wherein상기 발효물은 유산균과 효모로 이루어진 군으로부터 선택된 미생물에 의해 발효된 것을 특징으로 하는 조성물.The fermented product is characterized in that the fermented by a microorganism selected from the group consisting of lactic acid bacteria and yeast.
- 제 7항에 있어서, 상기 유산균은 락토바실러스 플란타룸 P23 (Lactobacillus plantarum P23)인 것을 특징으로 하는 조성물.The composition of claim 7, wherein the lactic acid bacteria is Lactobacillus plantarum P23.
- 제 7항에 있어서, 상기 효모는 Yeast DSII인 것을 특징으로 하는 조성물.8. The composition of claim 7, wherein said yeast is Yeast DSII.
- 지골피, 창출, 상심자를 포함하는 한약재의 발효물 또는 발효물의 추출물을 유효성분으로 함유하는 비만 또는 고지혈증의 예방 및 치료용 약학 조성물. A pharmaceutical composition for the prevention and treatment of obesity or hyperlipidemia, comprising a phalanx, an extract, a fermented product of the herb containing the heartache, or extracts of the fermented product as an active ingredient.
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