KR20060078125A - Extract of rumex japonicus, extract of rumex crispus and method of manufacture thereof - Google Patents

Abstract

The present invention relates to a sesame extract, a extract of the extract and a method for producing the sesame extract according to the present invention, dried and shredded sesame root, extracted with alcohol or an aqueous alcohol solution, and then filtered the extracted extract Characterized in that it is obtained by concentrating under reduced pressure, and the preparation method comprises the step of preparing a medicinal herb dried and shredded the root of Chamsori; An extraction step of extracting the shredded Chamsori root with any one of 30-100% methyl alcohol, ethyl alcohol or an aqueous alcohol solution; After filtering the extracted extract is characterized by consisting of a concentration step of concentration under reduced pressure.

In addition, the extract of the extract of the present invention according to the present invention is characterized in that after drying and cutting the root of the extract, extracted with an alcohol or an aqueous alcohol solution, and then obtained by filtration and concentrated under reduced pressure, the production method is the root of the extract Drying and cutting the medicine preparation step; An extraction step of extracting the shredded ground roots with any one of 30-100% methyl alcohol, ethyl alcohol or an aqueous alcohol solution; After filtering the extracted extract is characterized by consisting of a concentration step of concentration under reduced pressure.

In addition, the pharmaceutical composition for the prevention or treatment of diabetic complications and the functional food according to the present invention is characterized in that it contains the extract of Chamsori or Rinsu as an active ingredient.

In addition, the anti-aging or delaying pharmaceutical composition and functional food according to the present invention is characterized in that it contains the extract of Chamsori or Roksam as an active ingredient.

The mixed herbal extract of the present invention effectively inhibits the production of the final glycation end product which is one of the causative agents of diabetic complications, and thus may be applied to pharmaceutical compositions and functional foods for the prevention and treatment of diabetic complications and to prevent aging.

Chamsori, Jasmine, Final Glycolysate, Diabetic Complications

Description

Extract of Rumex japonicus, extract of Rumex japonicus and method of manufacture thereof             

1 is a graph showing the effect of inhibiting the production of the final glycation product of the Chamsori Jja extract according to the present invention,

Figure 2 is a graph showing the inhibitory effect of the final glycation product production of the extract of the extract according to the present invention,

3 is a graph showing the inhibitory effect of the final glycation product production of aminoguanidine as a control.

The present invention relates to the extract of Sesame, the extract of the extract and the method for producing the same, more specifically, using the extract obtained by extracting the root of Chamsori or the extract, the final glycation product that is one of the factors inducing diabetes mellitus The present invention relates to a sesame extract, an extract of the extract and an effective method for preventing or treating diabetic complications and preventing or delaying aging.

Diabetes is one of the world's most important adult diseases. Recently, with the rapid economic growth in Korea, the prevalence rate of diabetes reaches 7-8%, and it is a significant cause of death for people in their 60s and 70s. Diabetic complications, one of the causes of death from diabetes, cause damage to almost every organ in the body after 10-20 years of diabetes, resulting in diabetic retinopathy, diabetic cataract, and nephropathy. ) And diabetic neuropathy (Neuropathy).

In particular, chronic diabetic nephropathy is the most important cause of hemodialysis treatment and end stage renal failure, and there is no treatment other than hemodialysis treatment and organ transplantation. These diabetic complications can be seen in the case of diabetic treatment to recover the normal blood glucose level, which is the final glycated product irreversibly produced as a result of the non-enzymatic glycation reaction of the protein due to the persistent hyperglycemic state ( Advanced glycat ion endproducts (AGEs) are known as one of the main reasons.

Mechanisms that induce diabetic complications are largely explained by nonenzymatic glycation of proein, polyol pathway and oxidative stress.

Nonenzymatic glycation of protein refers to the condensation reaction of a group of amino acids such as lysine residues of protein and reducing sugars by condensation reaction or milliard reaction without enzymatic action. endproducts, AGEs). Non-enzymatic glycosylation of protein (1) an amino acid group such as a lysine residue of a protein and an aldehyde or ketone of a reducing sugar undergo a nucleophilic addition reaction without enzymatic action to form a Schiff base, an early product. Schiff base and contiguous ketoamine adduct condensate to produce reversible Amadori-type early glycosylated product, and (2) the hyperglycemic state persists, so that reversible Amadori-type early glycosylated product is not degraded. It can be divided into stages that are rearranged and cross-linked with proteins to produce irreversible final glycosylated products.

Unlike the reversible Amadori type of early glycosylated products, the final glycated products are irreversible reaction products. Once produced, blood sugars do not degrade even when they are restored to normal, but accumulate in the tissues during protein survival to abnormally change the structure and function of the tissues. (Vinson, JA et al., 1996, J. Nutritinal Biochemistry 7: 559-663; Smith, PR et al., 1992, Eur. J. Biochem ., 210: 729-739).

For example, glycated albumin, one of the final glycation products produced by reacting glucose with various proteins, is an important factor in causing chronic diabetic nephropathy. Glycosylated albumin is more easily introduced into renal glomeruli cells than normal albumin without glycosylation, and high concentrations of glucose stimulate mesangium cells to increase extracellular matrix synthesis. Excessly introduced glycated albumin and increased extracellular matrix result in fibrosis of the glomeruli. These mechanisms continue to damage the glomerulus, leading to the stage of extreme treatment methods such as hemodialysis or organ transplantation. In addition, chronic diabetes has been reported to accumulate collagen in the arterial wall and basal membrane protein in the renal glomeruli with the final glycation endogenous product (Brownlee, M., et al., 1986, Sciences , 232, 1629). -1632).

As described above, glycosylation occurs in proteins such as the basement membrane, plasma albumin, lens protein, fibrin, and collagen by non-enzymatic protein glycosylation reaction, and the resulting glycosylated product abnormally changes the structure and function of the diabetic retinopathy. ), Diabetes cataract, diabetic nephropathy (nephropathy), diabetes mellitus (Neuropathy) and other chronic diabetes complications.

In addition, the final glycosylated product produced by non-enzymatic protein glycosylation reaction is known to play an important role in aging (Monnier et all., Proc. Natl. Acad. Sci. USA, 81: 583, 1984; Lee et a1., Biochem.Biophys.Res.Comm., 123: 888, l984; Diabetologia, 38: 357-394).

As described above, the final glycosylated product produced in the non-enzymatic protein glycosylation reaction is a major cause of the progression of diabetes complications and aging, it is necessary to suppress the production of the final glycation products in order to prevent the progression of diabetes complications and aging.

Currently, aminoguanidine-HCl, the only synthetic agent for protein glycosylation inhibitors, is a nucleophilic hydrazine, which binds to the amadori product and prevents cross-linking with the protein, thereby inhibiting the formation of the final glycation product. Delay or prevent progression to Brownlee, M., et al., 1986, Sciences, 232, 1629-1632; Edelstein, D. et al., L992, Diabetes, 4l, 26-29. Amino guanidine-HCl is the most promising synthetic drug for the prevention and treatment of diabetic complications, but it has been conducted up to Phase III clinical trials, but there is a problem that toxicity is induced upon long-term administration.

Therefore, in recent years, due to the limitations of the development of disease treatments by conventional synthetic compounds, and problems related to side effects and toxicity during treatment, development of disease treatments based on herbal medicines has been actively progressed.

Accordingly, the present inventors have completed the present invention by discovering that the extract extracted from the roots of Chamsori and Roksam in alcohol can be used for the treatment and prevention of diabetic complications by inhibiting the production of the final glycation end products.

In order to solve the above problems, the present applicant has continuously studied the causes, prescriptions, and treatment methods of diabetic complications, and the present invention has the effect of inhibiting the production of the final glycated product, which is one of the causes of diabetic complications. The purpose is to provide a root extract of the ridden or ridden.

Another object of the present invention to provide a pharmaceutical composition for the prevention and treatment of diabetic complications or anti-aging and delaying containing the extract of Chamsori or Ryuksam as an active ingredient.

Still another object of the present invention is to provide a functional food for preventing and treating diabetic complications or delaying anti-aging madness, which contains the extract of Sesame creeper or larva as an active ingredient.

The chassam extract according to the present invention for achieving the object of the present invention is dried and shredded Chamsori root, and then extracted with an alcohol or an aqueous alcohol solution, it is characterized in that the extracted extract is filtered and concentrated under reduced pressure.

In addition, the extract of the extract of the present invention according to the present invention is characterized by being obtained by drying and cutting the root of the extract, extracted with an alcohol or an aqueous alcohol solution, and then filtered and concentrated under reduced pressure.

In addition, the pharmaceutical composition and functional food for preventing or treating diabetic complications according to the present invention is characterized in that it contains the extract of Sesame nyssia or extract of the larva as an active ingredient.

In addition, the anti-aging or delaying pharmaceutical composition and functional food according to the present invention is characterized in that it contains the extract of Sesame nyssia extract or extract.

Chamsori ridden (Rumex japonicus Houtt.) And curly dock (Rumex Crispus L.) used in the present invention is commonly grows in the wetlands of the country as a perennial plant belonging to polygonaceae (Polygonaceae), Japan, China, Asia, Europe, Distributed in Africa (Bae Gi-hwan, Korean medicinal plant, p 52, Kyohaksa, 2000).

In oriental medicine, the roots are called Yangje-geun (이 根) or Wuyi Rhubarb (牛耳 大黃), and rhubarb (大黃) substitutes are effective for blue blood, sheep blood, sputum, seaweed, and constipation. Treat the poison. The leaf is called Uidaehwangbyeol (牛耳 大 黃葉), and it has the effect of clearing and detoxifying (Lee Chang-bok, Korea Plant Book, p 297, Hyangmunsa, Seoul, 1989; Bae Hwan-hwan, Korean medicinal plant, p 52, Kyohaksa, Seoul , 2000).

Their roots contain anthraquinoids, including emodin, and naphthalene derivatives, including muzisin (Biopharmaceutical Research Society, Modern Biopharmaceuticals, p 320, Hakchangsa, Seoul, 1995) ).

Kim et al. Reported one anthraquinone compound and a naphthalene compound as a cytotoxic substance for several types of human cancer cell lines (Kim Dae-geun, et al., 42 , pp 233-). 237, 1998).

It has been reported that ether, ethanol and hot water extracts of the leaves and seeds of the oleander have DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging and antimicrobial activity (Yildirim, A et al, J). Agric Food Chem., 2001, Aug; 49 (8): 4083-9). However, there have been no studies on the preventive and inhibitory activities of diabetic complications and their active ingredients.

Hereinafter, the present invention will be described in detail.

I. Chamsori Extract

The extract of Chamsoomgi according to the present invention is obtained by drying and cutting the roots of Chamsori, which is extracted with an alcohol or an aqueous alcohol solution, and then the extracted extract is filtered and concentrated under reduced pressure.

The preparation method of the extract comprises the step of preparing the medicine to dry, shredded the root of Chamsori; An extraction step of extracting the shredded Chamsori root with any one of 30-100% methyl alcohol, ethyl alcohol or an aqueous alcohol solution; The extracted extract is filtered and concentrated under reduced pressure.

Referring to the manufacturing method of the Chamsori Jja extract in more detail as follows.

1. Preparation stage

First of all, dry the roots of the Chassis.

2. Extraction step

5 to 10 times (w / v) of 30 to 100% 소리 methyl alcohol, ethyl alcohol or an aqueous solution of the alcohol is added to extract 5 to 10 times (5 times) the root of the shredded Champs ulmus.

3. Concentration step

The extract is filtered and concentrated under reduced pressure. At this time, the temperature is maintained at 45 ℃ or less to prevent decomposition and hydrolysis of the components.

II. Whiteman Extract

The extract of the extract from the extract according to the present invention is obtained by drying and cutting the root of the extract, extracting with an alcohol or an aqueous alcohol solution, and then filtering the extracted extract and concentrating under reduced pressure.

The preparation method of the extract is a drug preparation step of drying and cutting the root of the oleander; An extraction step of extracting the shredded ground roots with any one of 30-100% methyl alcohol, ethyl alcohol or an aqueous alcohol solution; The extracted extract is filtered and concentrated under reduced pressure.

The detailed method of preparing the extract is the same except that the method of preparing the extract of Chamsori is used instead of the samseongri.

Insulin extracts of the present invention of Chameori or Rumbus inhibit intestinal glycosylation of bovine serum albumin (BSA), 50% inhibitory concentration of the final glycation product, that is IC ₅₀ value of 18.9 μg / ml, 21.74 μg / ml showed excellent production inhibitory effect.

III. Pharmaceutical Compositions Containing Chamsori or Rime Extract as Active Ingredients

The present invention relates to a pharmaceutical composition for preventing or treating diabetic complications and an anti-aging or delaying pharmaceutical composition containing an extract of Chamsori or Jassori as an active ingredient. It shows the therapeutic activity of diabetic complications or aging, such as inhibiting the production of the final glycation end product, which is the main cause of aging, and can be used orally or parenterally during clinical administration, and thus can be used in the form of general pharmaceutical preparations.

That is, the pharmaceutical composition of the present invention may be administered in various formulations during actual clinical administration, and when formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, etc. that are commonly used are used. It is prepared. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient such as starch, calcium carbonate, It is prepared by mixing sucrose or lactose, gelatin and the like.

In addition to simple excipients, lubricants such as magnesium styrate 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 the suspension solvent, 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.

IV. Functional foods containing Chamsori or Root Extract as active ingredients

The present invention relates to a functional food for the prevention or treatment of diabetic complications and an anti-aging or delayed functional food containing the extract of the roots of the chaksam or tomung as an active ingredient, the functional food Other food ingredients may be added depending on the merchandise and consumer preference of the final product.

When using such Chamsung or Rime extract as a food additive, the Chamsori or Rime extract can be added as it is or used with other foods or food ingredients, and can be suitably used according to conventional methods.

The mixed amount of the active ingredient may be suitably determined depending on the purpose of use (prevention, health or therapeutic treatment). Generally, in the preparation of food or beverages, the extract of Chamsori or Rootsmouth of the present invention is added in an amount of up to 15% by weight, preferably up to 10% by weight based on the raw materials. However, in the case of long-term intake for health and hygiene or for health control, the amount may be below the above range, and the active ingredient may be used in an amount above the above range because there is no problem in terms of safety. have.

There is no particular limitation on the kind of food. Examples of the food to which the substance can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, drinks, Alcoholic beverages, vitamin complexes, and the like, and includes all of the functional foods in a conventional sense.

The functional food of the present invention may contain various flavors, natural carbohydrates, and the like as additional ingredients, like ordinary beverages. The above-mentioned natural carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and sugar alcohols such as polysaccharides, xylitol, sorbitol and erythritol, and destrin, cyclodextrin and liver. As the sweetening agent, natural sweetening agents such as tautin and stevia extract, synthetic sweetening agents such as saccharin and aspartame, and the like can be used. The ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 ml of the extract of the present invention.

In addition to the above, the extract of the present invention may contain various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohols, carbonic acid. Carbonating agents and the like used in beverages. In addition, the composition of the present invention may contain a flesh for preparing natural fruit juice, fruit juice beverage and vegetable beverage. These components can be used independently or in combination. The proportion of such additives is not critical but is generally selected in the range of from 0.1 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.

It has been reported that abnormal metabolism of lipid metabolism occurs in the process of producing the final glycosylated product, and at the same time, the function of the defense system against harmful oxygen free radicals is deteriorated and oxidative stress is induced. Oxygen present in the body is converted into reactive oxygen radicals that are highly reactive by environmental and biochemical factors such as enzymes, reduction metabolism, chemicals, pollutants, and photochemical reactions. As irreversible destruction, the inhibition rate of oxidative stress is expected to be reduced if the production of the final glycation end products is suppressed.

Hereinafter, the present invention will be described in more detail by the following examples and experimental examples. However, the following Examples and Experimental Examples are merely illustrative of the contents of the present invention and the scope of the invention is not limited by the Examples and Experimental Examples.

Example 1

Rumex japonicus Houtt. And Rumex Crispus L. were collected and dried in Jeonmin-dong, Daejeon, and the roots were cut. Each sample was placed in 80% ethanol and extracted three times at room temperature in an extraction container for 7 days. The extracts were concentrated under reduced pressure to obtain the root extracts of Chassam and Jasmine. At this time, the water base (water bath) was maintained at 40 ~ 45 ℃ to prevent decomposition and hydrolysis of the components. Ethyl alcohol was completely removed by concentration under reduced pressure, and the water was completely dried in a freeze dryer. As a result of drying, 0.85 g of extract was obtained (yield: 10.6%).

Experimental Example 1 Analysis of Inhibitory Effect on the Production of Final Glycosylated Products in Vitro

Bovine serum albumin (hereinafter referred to as BSA: Sigma, USA) was selected as a protein source. BSA was prepared by adding 50 mM phosphate buffer (pH 7.4) to a concentration of 10 mg / ml. As a sugar source, a mixture of 0.1 M sugar and 0.1 M glucose was used. A fructose and glucose mixture was added to the prepared BSA solution. Root extracts of Chamsori and Rossori were sampled and dissolved in distilled water, which were then added to the mixture of BSA and sugar and incubated at 37 ° C. for 15 days. At this time 0.02% sodium azide was added as an antibacterial agent.

The control group was cultured with a mixture of BSA and sugar, and the blank group of the test group and the control group was prepared and not cultured. On the other hand, aminoguanidine was used as a positive control which is an index to compare the excellent efficacy. All cultures were prepared by four to avoid errors as much as possible, immediately before the culture was filled with nitrogen gas (purity: 99.999%) to prevent contamination. After 15 days, the content of the final glycation product produced in the culture was analyzed and the result was shown. The final glycosylated product is fluorescence, brown, not only has a physicochemical property that can cross-link, but also has a ligand that can be recognized by cell membrane receptors. The amount of final glycated product having these characteristics was measured by spectrofluorometer (Excitation: 350nm, Emission: 450nm) to analyze the degree of inhibition of production.

Experimental Example 2 Efficacy of Inhibiting the Final Glycosylated Product of Chassori Radix or Extracts

Cheongsori extract prepared in Example 1 was prepared at concentrations of 2.5 μg / ml, 5.0 μg / ml, and 25 μg / ml, and the extract of Example 1 in 10 μg / ml, 20 μg / ml, After preparing at a concentration of 25 μg / ml, the method described in Experiment 1 was incubated at 37 ° C. for 15 days. After 15 days, the amount of the final glycated product produced in the culture was measured by a spectrofluorometer (Excitation: 350 nm, Emission: 450 nm), and the results are shown in Table 1 and FIGS. 1 and 2.

The production inhibition rate is calculated by the following equation.

Production Inhibition Rate (%) = 100-(Fluorescence Intensity of Sample-Fluorescence Intensity of Sample Blank) / (Fluorescence Intensity of Control-Fluorescent Intensity of Control Blank) x100

Comparative Example 1 Efficacy of Inhibiting the Final Glycosylated Product of Aminoguanidine

Aminoguanidine was dissolved in distilled water, prepared at concentrations of 27.5 μg / ml, 55 μg / ml, 110 μg / ml, and 550 μg / ml, and then cultured at 37 ° C. for 15 days by the method described in Experimental Example 1. After 15 days, the amount of the final glycated product produced in the culture was measured with a spectrofluorometer (Excitation: 350 nm, Emission: 450 nm), and the results are shown in Table 1 and FIG. 2.

As shown in Table 1, the extracts of Cham-ryumpum extracts showed 7.92%, 11.67%, and 66.39%, respectively, at 2.5 μg / ml, 5 μg / ml, and 25 μg / ml, and the IC ₅₀ was 18.88 μg / ml. appear. The extracts of R. japonica extracts were 13.34%, 48.43%, and 57.39% at 10 ㎍ / ㎖, 20 ㎍ / ㎖ and 25 ㎍ / mL, respectively, and IC ₅₀ was 21.74 ㎍ / mL. It can be seen that the efficacy is superior to aminoguanidine (86.91 μg / ml).

As discussed above, the extract of Chamsori-ri or Kok-juk according to the present invention inhibits the production of the final glycation product, which is one of the causes of diabetic complications at a low concentration, significantly lower than the positive control aminoguanidine, in the production of the final glycation product. Application as a pharmaceutical composition and functional food for the prevention and treatment of diabetic complications, namely diabetic retinopathy, diabetic cataract, nephropathy, diabetic neuropathy, etc. Can be. In addition, the inhibition rate of oxidative stress is reduced when inhibiting the production of the end glycated product, it can be applied as a pharmaceutical composition and functional food for preventing and delaying aging caused by oxidative stress.

Claims (10)

After drying and cutting the root of Chamsori, the extract of Chamsori is obtained by filtering the extracted extract with filtration and concentration under reduced pressure. The method of claim 1, The alcohol or the aqueous alcohol solution is 30 ~ 100% of methyl alcohol, ethyl alcohol or an alcoholic solution of any one of the extracts. Drying and cutting off the roots of Chamsori medicinal herb preparation step; An extraction step of extracting the shredded Chamsori root with any one of 30-100% methyl alcohol, ethyl alcohol or an aqueous alcohol solution; The method of manufacturing Chamsori-ri which comprises a concentration step of filtration and extracting the extracted extract under reduced pressure. After drying and cutting the root of the larva, after extracting with alcohol or aqueous alcohol solution, the extract is obtained by filtration and concentration under reduced pressure. The method of claim 4, wherein The alcohol or aqueous alcohol solution is 30 to 100% methyl alcohol, ethyl alcohol or alcoholic extract of any one of the aqueous alcohol solution. A drug preparation step of drying and cutting the root of the pterosaur; An extraction step of extracting the shredded ground roots with any one of 30-100% methyl alcohol, ethyl alcohol or an aqueous alcohol solution; The method of producing a soybeans, characterized in that consisting of a concentration step of filtering and extracting the extracted extract under reduced pressure. A pharmaceutical composition for preventing or treating diabetic complications, comprising any one of claim 1 extract of claim 1 or extract of claim 4 as an active ingredient. The anti-aging or delaying pharmaceutical composition containing any one of the extract of Chamsori and the extract of claim 1 as an active ingredient. Functional food for the prevention or treatment of diabetic complications comprising any one of the extracts of claim 1 or the extract of claim 4 as an active ingredient. Anti-aging or delayed functional food containing any one of the extract of claim 1 or the extract of claim 4 as an active ingredient.

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