KR102558750B1 - A novel compound derived from psicose - Google Patents

Abstract

The present invention relates to a novel compound derived from psicose, and more specifically, to psicose 2_molecule-linked compounds and derivatives with advanced glycation end product reduction activity, and to food compositions, pharmaceutical compositions, and feed compositions that can prevent, alleviate, or treat diseases related to advanced glycation end products comprising the same.

Description

A novel compound derived from psicose}

The present invention relates to a novel psicose-derived compound, and more particularly, to a compound in which psicose 2_molecules are connected having an activity of reducing end-products of glycation, and a composition containing the same.

Psicose is a monosaccharide that does not exist in nature and is produced from fructose by epimerase. Psicose is known to have effects such as insulin resistance, strengthening and forming antioxidants, and controlling hypoglycemia (O’Donnell, Claudia, “Formulating for a Sweet Perception With Natural Sweeteners”).

Advanced glycation end products (AGEs) are substances produced when blood glucose combines with blood proteins such as hemoglobin, LDL, and collagen, and are a major cause of diabetic complications.

AGEs, such as glyoxal, methylglyoxal, and 3-deoxyglucosone, are difficult to degrade once produced, and are not degraded even after normal blood sugar levels are restored. They bind to blood proteins or various tissues and cause organ damage.

Representative substances that inhibit the production of AGEs include aminoguanidine, pyridoxamin, ALT-711, N-phenacylthiazolium bromide (PTB), and thiazolidinediones. In addition, antioxidants derived from natural products also show the effect of reducing AGEs. Natural products that can be eaten have low concerns about toxicity and side effects, but have a problem that their efficacy is lower than synthetic materials, so there is a need to develop new materials that are non-toxic to cells and have excellent AGEs reduction efficacy.

Republic of Korea Patent Publication No. 10-2019-0111839

One object of the present invention is to provide a novel psicose-derived compound having structural features capable of reducing advanced glycation end products (AGEs).

Another object of the present invention is to provide a food composition for preventing or improving advanced glycation end product-related diseases comprising the psicose-derived compound as an active ingredient.

Another object of the present invention is to provide a health functional food comprising the food composition.

Another object of the present invention is to provide a food additive composition comprising the psicose-derived compound as an active ingredient.

Another object of the present invention is to provide a feed composition having final glycation end product reduction activity, containing the psicose-derived compound as an active ingredient.

Another object of the present invention is to provide a pharmaceutical composition for preventing or treating advanced glycation end products-related diseases, comprising the psicose-derived compound as an active ingredient.

Another object of the present invention is to provide a method for preparing a dipsicose dianhydride compound.

The technical problem to be achieved by the psicose-derived compound according to the technical idea of the present invention is not limited to the above-mentioned problem, and another problem not mentioned above will be clearly understood by those skilled in the art from the description below.

A detailed description of this is as follows. Meanwhile, each description and embodiment disclosed in this application may also be applied to each other description and embodiment. That is, all combinations of the various elements disclosed in this application fall within the scope of the present invention. In addition, it cannot be seen that the scope of the present invention is limited by the specific descriptions described below.

As one aspect for achieving the above object, the present invention provides a dipsicose dianhydride compound and a derivative thereof.

In the present invention, the term psicose is a compound also known as allulose or psicose, and refers to a C-3 epimer of fructose, a type of ketohexose.

The psicose molecule of the present invention may have a linear or cyclic structure, and as is known in the art, carbon numbers may be numbered in order close to the ketone group, and the carbon having the ketone group may be numbered as carbon number 2.

The psicose of the present invention may be extracted from natural substances or prepared by a chemical synthesis method or a biological method using an enzyme, but is not limited thereto.

The psicose of the present invention may be either L-type or D-type, and all psicose 2_ molecules may be L-type or D-type, or L-type or D-type, respectively.

When the psicose is not bound to other psicose molecules or other saccharides, it may be referred to as "monosaccharide psicose", "psicose monosaccharide", "psicose monosaccharide", or "psicose", but is not limited thereto.

In the present invention, the term “derivative thereof” refers to a salt thereof, a pharmaceutically acceptable salt thereof, an ester thereof, a free acid form thereof, a free base form thereof, a solvate thereof, a co-crystal thereof, a deuterated derivative thereof, a hydrate thereof, an N-oxide thereof, a clathrate thereof, a prodrug thereof, a polymorph thereof, a stereoisomer thereof, a geometric isomer thereof, a tautomer thereof, a mixture of tautomers thereof, and an enantiomer thereof. Isomers, diastereomers thereof, racemates thereof, mixtures of stereoisomers thereof, isotopes thereof (eg, tritium, deuterium), or combinations thereof.

"Pharmaceutically acceptable" means that the carrier, diluent or excipient must be compatible with the other ingredients of the pharmaceutical composition and must not be injurious to its recipient.

In the present invention, the term "pharmaceutically acceptable salt" refers to a salt prepared from a base or acid that is acceptable for administration to a patient such as a mammal. The term “pharmaceutically acceptable salts” includes salts commonly used to form alkali metal salts and addition salts of free acids or free bases. The nature of the salt is not critical as long as it is pharmaceutically acceptable. Such salts may be derived from pharmaceutically acceptable inorganic or organic bases and pharmaceutically acceptable inorganic or organic acids.

In the present invention, the term "substitution" means that a hydrogen atom bonded to a carbon atom of a compound is replaced with another substituent, and the position to be substituted is not limited as long as the hydrogen atom is substituted, that is, a position where the substituent can be substituted. In the case of two or more substitutions, two or more substituents may be the same or different from each other.

In the present invention, the term “substituted or unsubstituted” refers to deuterium (-D); halogen group; nitrile group; nitro group; hydroxy group; silyl group; boron group; alkoxy group; an alkyl group; cycloalkyl group; aryl group; And it means that it is substituted with one or two or more substituents selected from the group consisting of a heterocyclic group, or is substituted with a substituent in which two or more substituents from among the above exemplified substituents are connected, or does not have any substituents. For example, "a substituent in which two or more substituents are connected" may be a biphenyl group. That is, the biphenyl group may be an aryl group or may be interpreted as a substituent in which two phenyl groups are connected.

In the present invention, "halo" or "halogen" refers to bromo (Br), chloro (Cl), fluoro (F), or iodo (I), and the preferred halogen as a substituent may be fluoro or chloro.

In the present invention, "alkyl group" represents, for example, a saturated aliphatic hydrocarbon group such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl and tert-butyl, which may or may not have a substituent. The additional substituent in the case of being substituted is not particularly limited, and examples thereof include an alkyl group, a halogen group, an aryl group, and a heteroaryl group, and this point is also common to the description below. The number of carbon atoms in the alkyl group is not particularly limited, but is preferably 1 or more and 10 or less, more preferably 1 or more and 4 or less, from the viewpoint of availability and cost.

In the present invention, "alkoxy group" refers to a functional group to which an aliphatic hydrocarbon group is bonded via an ether bond such as, for example, a methoxy group, an ethoxy group, or a propoxy group, and the aliphatic hydrocarbon group may or may not have a substituent. The number of carbon atoms in the alkoxy group is not particularly limited, but is preferably 1 or more and 10 or less, more preferably 1 or more and 4 or less.

In the present invention, the term "combination of these" included in the expression of the Markush form means a mixture or combination of one or more selected from the group consisting of the components described in the expression of the Markush form, and includes one or more selected from the group consisting of the components.

According to one embodiment, the derivative may refer to a dipiccose dianhydride compound substituted with a functional group such as a halogen group or an alkyl group (particularly, excluding sugars).

In the present invention, the term "glycosidic bond" refers to an ether-type bond formed between a hemiacetal hydroxyl group of a sugar and a functional group such as various alcohols, phenols, carboxylic acids, aldehydes, etc. Specifically, it may be a bond used to bond two monosaccharide molecules into a disaccharide.

In the present invention, the term "compound in which psicose 2_ molecules are linked by a glycosidic bond" may be used interchangeably with terms such as "psicose disaccharide", "psicose diploid", and "psicose disaccharide".

According to one embodiment, the compound of the present invention may have two anhydride bonds in which psicose 2_ molecules are connected.

The compound according to the present invention has an excellent effect of removing glycation products generated from hyperglycemia when cell functions are reduced.

According to one embodiment of the present invention, a compound in which psicose 2_ molecules are linked by two glycosidic bonds is provided.

According to one embodiment, the glycosidic bond may be a form in which the hydroxy group of carbon 2 (C2) and the hydroxy group of carbon 1 (C1) of molecule 1 of psicose 2_in the molecule of psicose 2 are glycosidic bonded to the hydroxy group of carbon 1 and the hydroxy group of carbon 2 of another molecule of psicose 1, respectively, but is not limited thereto.

According to one embodiment, one molecule of the psicose 2_ molecule may be in the form of psicofuranose and the other molecule may be in the form of psicopyranose, but is not limited thereto.

According to one embodiment of the present invention, a compound in which psicose 2_ molecules are connected, the compound is represented by the following formula (1):

[Formula 1]

According to one embodiment, the compound is α-psicofuranosyl -psicopyranosyl (α-psicofuranosyl β-psicopyranosyl), α-psicofuranosyl -psicofuranosyl (α-psicofuranosyl β-psicofuranosyl), α-psicopyranosyl -psicopyranosyl (α-psicopyranosyl β-psicopyranosyl), α-psicopyranosyl -psicofuranosyl, α-psicofuranosyl, α-psicopyranosyl, α-psicofuranosyl, α-psicofuranosyl, α-psicopyranosyl, α-psicopyranosyl, pyranosyl α-psicopyranosyl), β-psicofuranosyl -psicopyranosyl (β-psicofuranosyl β-psicopyranosyl), β-psicofuranosyl -psicofuranosyl (β-psicofuranosyl β-psicofuranosyl) or β-psicopyranosyl -psicopyranosyl (β-psicopyranosyl β-psicopyranosyl). The compound may be a combination of alpha-D-(2S,3R,4R,5R)-2-(HYDROXYMETHYL)OXANE-2,3,4,5-tetrol and beta-D-(2S,3R,4S,5R)-2,5-bis(hydroxymethyl)oxolane-2,3,4-triol.

According to one embodiment, the compound may be a compound represented by Formula 2 below:

[Formula 2]

5 is a molecular structural formula of the compound represented by Chemical Formula 2 in the Howard projection formula. Referring to FIG. 5 , a pentose sugar forms an alpha bond and a hexose sugar forms a beta bond around two anhydride bonds.

The present invention also provides a composition comprising the compound according to one embodiment of the present invention as an active ingredient. The composition is excellent in removing glycation products generated from hyperglycemia when cell function is reduced.

The concentration of the compound in the composition containing the compound according to one embodiment of the present invention may be greater than or equal to 0.01 μM and less than 10 μM. More specifically, the concentration of the compound may be 0.01 μM to 5 μM, preferably 1 μM to 5 μM.

Here, there is a problem in that cytotoxicity appears when the concentration of the compound exceeds 1 μM. In addition, when the concentration is less than 0.01 μM, there is a problem in that the effect of reducing (degrading) activity of advanced glycation products may be insignificant.

As another aspect for achieving the above object, the present invention provides a food composition having final glycation end product "reduction" activity, including the compound according to one embodiment of the present invention as an active ingredient.

The present invention also provides a food composition for preventing or improving final glycation end product-related diseases comprising the compound according to an embodiment of the present invention as an active ingredient; And it provides a health functional food containing the food composition.

The term "active ingredient" of the present invention refers to a component that exhibits the desired activity alone or that can exhibit activity together with a carrier having no activity itself.

The term "final glycation product" of the present invention refers to a substance formed through various processes by a reaction between protein and sugar and glycation. The saccharification reaction occurs almost spontaneously without energy supply and has an irreversible characteristic after a certain stage in food or the body. In the body, it reacts with various protein components such as glucose or its breakdown products in the blood, hemoglobin, LDL, collagen, etc. to produce various kinds of advanced glycation end products. Accumulated advanced glycation end products interact with advanced glycation end receptors to accumulate inflammatory cells, increase the secretion of growth-promoting cytokines and increase cell death, accumulate in tissues during the life of proteins, abnormally change the structure and function of tissues, and are known to cause various diseases such as metabolic diseases, diabetes, diabetic complications, Alzheimer's, arteriosclerosis, uremia, microvascular disease, macrovascular disease, cataract, Parkinson's, aging or cancer.

The food composition of the present invention may contain the compounds in various amounts, as long as they have final saccharified product 　reduction 　activity.

In addition to the above compounds, the food composition of the present invention may further include any compound or natural extract whose safety has already been verified in the art and is known to have a corresponding activity, in order to enhance the convenience of taking or ingesting.

These compounds or extracts include compounds or extracts listed in official compendia such as the Pharmacopoeia of each country ('Korean Pharmacopoeia' in Korea) and the Health Functional Food Codex of each country ('Health Functional Food Standards and Specifications', a notice of the Ministry of Food and Drug Safety in Korea), compounds or extracts for which items have been approved under each country's laws governing the manufacture and sale of pharmaceuticals ('Pharmaceutical Affairs Act' in Korea), and compounds or extracts whose functionality has been recognized under each country's laws governing the manufacture and sale of health functional foods ('Health Functional Foods Act' in Korea). can be included

The term “food” of the present invention includes meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, vitamin complexes, nutritional supplements, functional foods, food additives, health functional foods, and health foods, and includes all foods in a conventional sense.

The health food (health food) means a food having an active health maintenance or promotion effect compared to general food, health supplement food (health supplement food) means a food for the purpose of health supplement. In some cases, the terms health functional food, health food, and health supplement food are used interchangeably.

The term "health functional food" of the present invention is the same term as food for special health use (FoSHU), and refers to food with high medical and medical effects processed to efficiently display bioregulatory functions in addition to nutrient supply. Here, "function (sex)" means to obtain useful effects for health purposes such as regulating nutrients for the structure and function of the human body or physiological functions. The food of the present invention can be prepared by a method commonly used in the art, and can be prepared by adding raw materials and ingredients commonly added in the art during the preparation. In addition, the formulation of the food may also be prepared without limitation as long as the formulation is recognized as a food. The food composition of the present invention can be prepared in various types of formulations, and unlike general drugs, it uses food as a raw material and has the advantage of not having side effects that may occur when taking the drug for a long time, and has excellent portability.

Specifically, the health functional food is a food prepared by adding the compound to food materials such as beverages, teas, spices, chewing gum, confectionery, etc., or manufactured into pills, tablets, capsules, powders, suspensions, etc. When ingested, it means to bring about a specific effect on health, but unlike general drugs, there is an advantage that there is no side effect that may occur when taking a drug for a long period of time using food as a raw material.

Since the food composition of the present invention can be consumed on a daily basis, it is very useful because it can expect an effect of reducing advanced glycation end products in the body through reduction of end glycation end product production and degradation of end glycation end products.

The food composition of the present invention may be prepared in any form, for example, beverages such as tea, juice, carbonated beverages, and ionic beverages, processed oils such as milk and yogurt, gum, rice cakes, Korean sweets, bread, snacks, noodles, tablets, capsules, pills, granules, liquids, powders, flakes, pastes, syrups, gels, jellies, and bars. In addition, the food composition of the present invention may take any product classification as long as it conforms to the enforcement regulations at the time of manufacture and distribution in legal and functional classification. For example, it is a health functional food according to the 'Health Functional Food Act' of Korea, or confectionery according to each food type according to the Food Code of the 'Food Sanitation Act' (Ministry of Food and Drug Safety Notice 'Food Standards and Specifications').

In addition, the food composition of the present invention may include food additives in addition to the active ingredient. Food additives may generally be understood as substances that are added to, mixed with, or infiltrated into food in manufacturing, processing, or preserving food. Since food is consumed daily and for a long period of time, its safety must be guaranteed. These food additives are classified into sweeteners, flavor enhancers, preservatives, emulsifiers, flavoring agents, and the like in terms of use.

The sweetener is used to impart an appropriate sweetness to food, and may be natural or synthetic. For example, sweeteners such as neotame, lactitol, D-ribose, mannitol, D-maltitol, and sodium saccharin may be used.

The flavor enhancer is a food additive that enhances the taste or aroma of food, and both natural and synthetic additives may be used. For example, flavor enhancers may include disodium 5'-guanylate, L-glutamic acid, glycine, and betaine.

As the preservative, sodium metabisulfite, anhydrous sulfurous acid, sorbic acid, benzoic acid, grapefruit seed extract and the like may be used.

The emulsifier is a food additive that homogeneously mixes or maintains two or more immiscible phases such as water and oil, and sodium gluconate, glycerin fatty acid ester, lecithin, magnesium stearate, alginic acid, and the like can be used.

The flavor is a food additive that imparts a unique flavor to food or reinforces the original flavor of food lost during the manufacturing process, and ethyl vanillin, ethyl octanoate, linalyl acetate, allyl caproate, paramethylacetophenone, and the like may be used.

In addition to the food additives described above, the food composition of the present invention may include physiologically active substances or minerals known in the art and whose stability is guaranteed as food additives for the purpose of supplementing or reinforcing functionality and nutrition. Examples of the physiologically active substances include catechins contained in green tea, vitamins such as vitamin B1, vitamin C, vitamin E, and vitamin B12, tocopherol, dibenzoylthiamine, and the like, and minerals include calcium preparations such as calcium citrate, magnesium preparations such as magnesium stearate, iron preparations such as iron citrate, chromium chloride, potassium iodine, selenium, germanium, vanadium, zinc, and the like.

The food composition of the present invention may include the food additives described above in an appropriate amount to achieve the purpose according to the product type, and with respect to other food additives that may be included in the food composition of the present invention, each country's food code or food additives code may be referred to.

As another aspect for achieving the above object, the present invention provides a food composition for preventing or improving advanced glycation products-related diseases, for controlling blood pressure, for improving cholesterol, for improving joint or bone health, for blood sugar control, for improving triglycerides in blood, for improving skin conditions, for antioxidants, or for anti-inflammatory diseases, containing the compound according to one embodiment of the present invention as an active ingredient; And it provides a health functional food containing the food composition.

The term "diabetes related to advanced glycation end products" of the present invention may include any disease that can be caused by advanced glycation end products, and specifically, but is not limited thereto, metabolic diseases, diabetes, diabetic complications, insulin resistance syndrome, aging, Alzheimer's, Parkinson's, cancer, chronic kidney disease, heart disease, vascular disease, uremia, or rheumatoid arthritis.

The metabolic disease refers to diseases caused by metabolic abnormalities in vivo, such as sugars, lipids, proteins, vitamins, and minerals, and may include diabetes, obesity, non-alcoholic fatty liver, non-alcoholic steatohepatitis, hyperlipidemia, hypertension, and hyperinsulinemia, but is not limited thereto.

It has been reported that advanced glycation end products induce metabolic dysfunction, diabetes and obesity by activating inflammatory pathways, inducing oxidative stress, inducing damaged mitochondrial oxidative metabolism, promoting insulin resistance, or inducing pancreatic β-cell dysfunction (SERGI, Domenico, et al. Molecular Nutrition & Food Research , 2020). (ANGOORANI, Pooneh, et al. International Journal of Food Sciences and Nutrition , 2016, 67.2: 170-176.).

In addition, advanced glycation endproducts activate the receptor for advanced glycation endproducts (RAGE) present in Kupffer cells and hepatic stellate cells, and fatty liver exposed to advanced glycation endproducts responds with increased oxidative stress and inflammation, and has been reported to induce non-alcoholic fatty liver (FERNANDO, Dinali H., et al. International journal of molecular sciences , 2019, 20.20: 5037.). In a high fat, high fructose, high cholesterol diet (HFHC) model of nonalcoholic fatty liver, it was found that liver damage, nonalcoholic steatohepatitis, and liver fibrosis could be controlled by controlling the intake of advanced glycated end products (LEUNG, Christopher, et al. World journal of gastroenterology , 2016, 22.35: 8026.).

In addition, advanced glycation end products have been reported in many studies that are closely related to the progression of hyperlipidemia, hypertension and hyperinsulinemia (LIN, Reigh-Yi, et al. Atherosclerosis , 2002, 163.2: 303-311.; and CROFTS, Catherine, et al. Diabesity , 2015, 1.4: 34-43.). For example, advanced glycation end products act directly through their receptors to alter the function of many intracellular and extracellular proteins, including antioxidant and metabolic enzymes, calcium channels, lipoproteins, transcriptional and structural proteins, which have been shown to affect vascular (arterial) structure and function, and lead to endothelial dysfunction, inflammation and oxidative stress that are hallmarks of hypertension and atherosclerosis. In addition, reduction of advanced glycation end products has been demonstrated to be effective in reducing oxidative stress, reducing blood pressure and reducing atherosclerotic vascular changes (PRASAD, Kailash; MISHRA, Manish. The International journal of angiology: official publication of the International College of Angiology, Inc , 2017, 26.1: 1.; and VASDEV, Sudesh; GILL, Vicki; SINGAL, Pawan. Cell Biochemistry and Biophysics , 2007, 49.1: 48-63.).

The diabetic complications refer to symptoms caused when diabetes lasts for a long time, and diabetic complications are different from the onset criteria and judgment criteria of diabetes, and diabetic complications treatments are used separately from diabetes treatments. Since the causes of diabetic complications are caused by advanced glycation endproducts (AGEs) and abnormal activity of aldose reductase and accelerated oxidative stress, substances having advanced glycation end products reducing activity can be used as a treatment for diabetic complications. Diseases belonging to the diabetic complications include, but are not limited to, diabetic retinopathy, diabetic cataract, diabetic nephropathy, diabetic neuropathy, diabetic foot ulcer, diabetic heart disease, diabetic osteoporosis or diabetic arteriosclerosis.

It is known that glycosylation of proteins disrupts normal functions by destroying molecular shapes, altering enzyme activities, and interfering with receptor functions, and advanced glycation end products form intracellular and extracellular cross-links with other endogenous key molecules, including lipids and nucleic acids, as well as proteins, contributing to the development of diabetic complications (SINGH, Varun Parkash, et al. The Korean Journal of Physiology & Pharmacology , 2014, 18.1: 1-14.). 구체적으로, 증가된 단백질의 당화 및 최종당화산물의 축적은 세포 내 신호 전달 경로와 전염증성 및 경화성 사이토카인의 생성을 활성화시키는 것으로 연구된 바 있으며, 이러한 최종당화산물의 작용은 당뇨망막병증, 당뇨병성 백내장, 당뇨병성 신장질환, 당뇨병성 신경병증, 당뇨병성 심근병증, 당뇨병성 혈관 합병증, 당뇨병 환자의 골 취약성 및 골다공증, 당뇨병성 동맥경화 및 당뇨병성 심근경색을 포함하는 당뇨합병증의 발생 및 진행을 촉진시키는 것으로 보고된 바 있다(GOH, Su-Yen; COOPER, Mark E. The Journal of Clinical Endocrinology & Metabolism , 2008, 93.4: 1143-1152.; YAMAMOTO, Masahiro; SUGIMOTO, Toshitsugu. Current osteoporosis reports , 2016, 14.6: 320-326.; MEERWALDT, R., et al. Diabetologia , 2005, 48.8: 1637-1644.; LLAURADΣ, Gemma, et al. J Endocrinol , 2014, 221.3: 405-413.; 및 BAIDOSHVILI, A., et al. Arteriosclerosis, thrombosis, and vascular biology , 2006, 26.11: 2497-2503.).

The insulin resistance means that cells cannot effectively burn glucose due to a decrease in the function of insulin to lower blood sugar. When insulin resistance is high, the body produces excessive insulin, which can lead to high blood pressure, dyslipidemia, heart disease, diabetes, and the like. In particular, in type 2 diabetes, the increase in insulin in muscle and adipose tissue is not noticed, so the action of insulin does not occur. It is also known that insulin resistance, along with risk factors such as hypertension, diabetes, and smoking, increases intracellular oxidative stress and alters the signal transduction system to induce an inflammatory response to progress atherosclerosis (Freeman BA et al., 1982, Lab. Invest. 47:412-26 , Kawamura M et al., 1994, J. Clin. Invest. 94:771-8).

The insulin resistance syndrome is a concept that collectively refers to diseases caused by the insulin resistance, and refers to diseases characterized by cellular resistance to insulin action, hyperinsulinemia, increased very low density lipoprotein (VLDL) and triglyceride, decreased high density lipoprotein (HDL), and hypertension, etc., and is a concept recognized as a risk factor for cardiovascular disease and type 2 diabetes (Reaven GM., Diabetes ,　1988, 37:1595-607). Specifically, the insulin resistance syndrome may be obesity due to insulin resistance, hypertension, arteriosclerosis, hyperlipidemia, hyperinsulinemia, non-alcoholic fatty liver or type 2 diabetes, but is not limited thereto.

Regarding insulin resistance, it has been reported that there is a correlation between the level of advanced glycation end products and insulin resistance even in healthy conditions without obesity or diabetes (Tan et al., Diabetes Metab. Res. Rev. 2011; 27: 488-492.). In addition, it has been shown that restriction of advanced glycation end through dietary control reduces insulin levels, indicators of insulin resistance, and inflammation (Uribarri et al., Diabetes Care, 2011.07, 34: 1610-1616), and through several in vitro and in vivo studies on the relationship between advanced glycation end products and insulin resistance, it has been reported that limiting the accumulation and activity of advanced glycation end will help prevent insulin resistance and insulin resistance syndrome (S ong et al., Arteriosclerosis, thrombosis, and vascular biology , 2012, 32.8: 1760-1765).

The aging is a concept that generally encompasses declining changes in the structure and function of the body with age, and changes due to aging include a decrease in the weight and weight of each tissue due to a decrease in the number of parenchymal cells, a change in connective tissue, a change in body composition, a decrease in elasticity such as blood vessels or skin, a decrease in each organ function, a decrease in anti-disease recovery ability including immune ability, a decrease in sensory function, memory, learning ability and comparative ability. The aging may include at least one aging from the group consisting of muscle aging, skin aging, blood vessel aging, eye or vision aging, hearing aging, digestive organ aging, immune aging, and urinary organ aging, but is not limited thereto. Specifically, eye aging may refer to geriatric eye diseases such as cataract, glaucoma, or macular degeneration.

The effects of advanced glycation end products on aging-related diseases such as Alzheimer's disease, Parkinson's disease and cataract have been studied, and it has been reported that the level of advanced glycation end products (e.g., CML) and age-related diseases such as age-related macular degeneration or cataract have a positive correlation (SADOWSKA-BARTOSZ, Izabela; BARTOSZ, Grzegorz. Mechanisms of Aging and Development , 2016, 160: 1-18. ;STANISLOVAITIENΛ, Daiva, et al. Medicina , 2016, 52.2: 99-103.; and GUL, Anjuman, et al. Journal of Diabetes and its Complications , 2009, 23.5: 343-348.).

Advanced glycation end products have been reported to be associated with aging-related diseases (diabetes, cardiovascular disease, kidney disease, obesity, osteoporosis, cancer, intestinal microbiome-related diseases, neurodegenerative diseases, Alzheimer's, Parkinson's, and liver diseases). The accumulation of advanced glycation end products and the interaction between advanced glycation end products and advanced glycation end glycate receptors interfere with cell signaling pathways and play a causative role in various aging-related diseases, resulting in their inactivation and pathophysiology in many tissues or organs. It has been reported to contribute to science (Rungratanawanich et al., Experimental & Molecular Medicine , 2021, 53:168-188).

In addition, it has been observed that advanced glycation end products accumulate in the skin as aging progresses, and a correlation between skin aging and advanced glycation end products has been reported (Gkogkolou et al., Dermato-Endocrinology , 2012, 4(3): 259-270).

In addition, some studies found a relationship between advanced glycation end products and muscle function in the elderly, confirming that advanced glycation end products affect the decline in muscle function observed in aging. In other studies, it was observed that women with high CML concentration showed lower grip strength than women with low CML concentration, confirming that muscle weakness appears more in people with high levels of advanced glycation end (Luevano-Contreras et al., Nutrients, 2010, 2:124 7-1265). Additionally, in a study on mice, the amount of CML accumulation in skeletal muscle increased in mice fed a diet rich in advanced glycation end products, and as the amount of CML accumulation increased, skeletal muscle functions such as skeletal muscle mass, muscle strength and fatigue resistance were confirmed to decrease, and it was reported that high levels of advanced glycation end products can impair skeletal muscle development (Egawa et al., British Journal of Nutrition , 2017, 117.1: 21-29.).

Alzheimer's disease (AD) is the most common degenerative brain disease that causes dementia, and is usually chronic and progressive, and refers to multiple disorders of brain function including memory, thinking, learning ability, language and judgment. Since advanced glycation end products induce neurodegeneration according to the interaction with advanced glycation end products (RAGE), they are related to Alzheimer's disease, and studies have been conducted on the Alzheimer's onset mechanism of advanced glycation end products (KO, Shun-Yao, et al. PLoS One , 2015, 10.11: e0143345.). For example, the AGE-RAGE axis has been reported to induce Alzheimer's by increasing Aβ _1-42 formation and tau phosphorylation through increased cathepsin B and asparagine endopeptidase (BATKULWAR, Kedar, et al. ACS chemical neuroscience , 2018, 9.5: 988-1000 .).

Parkinson's disease is a chronic progressive degenerative brain disease of the nervous system caused by the loss of dopaminergic neurons. The role of protein glycation in neurodegenerative diseases such as Parkinson's has been studied (MIRANDA, Hugo Vicente; OUTEIRO, Tiago Fleming. The Journal of pathology , 2010, 221.1: 13-25.), It has been reported that reducing drugs show protective activity in both Parkinson's disease and diabetes (KOENIG, Annekatrin; VICENTE MIRANDA, Hugo; OUTEIRO, Tiago Fleming. Journal of Parkinson's disease , 2018, 8.1: 33-43.).

The cancer is a general term for diseases caused by abnormal cell growth, and is also referred to as a tumor. The role of advanced glycation end product receptor (RAGE) has been studied in various types of cancer. RAGE increases the number of cancer cells by activating cascading pathways including activation of cell cycle proteins (e.g. cyclin D1), anti-apoptotic proteins (e.g. BCl ₂ ), prosurvival (AKT) and autoophagic proteins, is involved in the progression of various types of cancer and cancer complications, and plays an important role in angiogenesis in tissues. It has been reported to suppress the immune response by activating myeloid derived suppressor cells (MDSC) (MALIK, Parth, et al. Biochimica et Biophysica Acta (BBA)-General Subjects , 2015, 1850.9: 1898-1904.).

The chronic kidney disease (CKD) refers to a state in which proteinuria is continuously present, there is evidence of kidney damage such as hematuria, or kidney function is continuously reduced for more than 3 months. Chronic renal failure (CRF) is defined as chronic renal failure when renal function declines below 50% for more than 3 months, and has a narrower meaning than chronic renal disease. Subjective symptoms include polyuria, swelling around the eyes and lower extremities, lethargy, fatigue easily, no appetite, nausea, itchy skin, bad breath (symptoms of ammonia odor), accompanied by symptoms of anemia and high blood pressure, and children may experience delayed growth and poor complexion. Research has been conducted on the correlation between advanced glycation end products and chronic kidney disease, and studies have been reported that they accumulate in patients with advanced glycation end products, amplify monocyte disruption by binding to advanced glycation end products receptors, and contribute to monocyte-mediated systemic inflammation related to renal failure (LINDEN, Ellena, et al. Clinical Journal of the American Society of Nephrology , 2008, 3.3: 691-698.; and HOU, Fan Fan, et al. Journal of the American Society of Nephrology , 2004, 15.7: 1889-1896.).

The heart disease is a general term for diseases occurring in the heart, and the heart disease may be insufficiency, cardiac hypertrophy, cardiac fibrosis, angina pectoris, myocardial infarction, arteriosclerosis, heart valve disease, hypertension, hypotension, cor pulmonale, arrhythmia, ventricular fibrillation, pericarditis, or endocarditis, but is not limited thereto.

N(ε)-carboxymethyllysine (CML) is a major advanced glycation end product. Plasma CML is elevated in aging, atherosclerosis and/or diabetes, and is known to be involved in the pathogenesis of heart disease. It has been reported that cardiac CML concentration increases with age, diabetes and/or coronary artery disease, and has a positive correlation with plasma CML concentration (HU, Shengda, et al. The Tohoku journal of experimental medicine , 2013, 230.1: 25-32.).

The vascular disease refers to all diseases in which blood flow and blood flow are abnormal due to damage or loss of vascular tissue due to various damages, including physical, oxidative and inflammatory damage, to vascular endothelial cells. The vascular disease may include arteriosclerosis, hypertension, coronary artery disease, cerebrovascular disease, peripheral vascular disease, aortic disease, cerebral infarction, myocardial infarction, peripheral blood circulation disorder, and ischemic encephalopathy, but is not limited thereto. CML, a major advanced glycation end product, is associated with an increased risk of cardiovascular disease (KIZER, Jorge R., et al. Atherosclerosis , 2014, 235.1: 116-121.), and CML levels reflect the presence of atherosclerosis in the coronary arteries (STANISLOVAITIENΛ, Daiva, et al. Medicina , 2016, 52.2: 99-1 03.) has been reported.

The uremia refers to various symptoms in which waste products to be excreted in the urine through the kidneys are not excreted and accumulated in the body, and advanced glycation products, which are the result of the Maillard reaction in vivo, have been reported to play an important role in various diseases including normoglycemic uremia (HENNING, Christian, et al. Journal of Biological Chemistry , 2011, 286.52: 44 350-44356.).

The rheumatoid arthritis (RA) is a chronic inflammatory disease in which inflammation appears in various joints, including the hands and wrists, feet and ankles. The relationship between advanced glycation end product accumulation and rheumatoid arthritis has been studied. In RA joints, overexpression of cytokines such as IL-1 and RAGE ligand increases the expression of advanced glycation end product receptor (RAGE) in tissue macrophages, which amplifies the inflammatory response through RAGE-ligand interaction, and it has been reported that high levels of RAGE expression in the vascular system promote infiltration of monocytes and lymphocytes into synovial tissue (ST) (SUNAHORI, Katsue, et al. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology , 2006, 54.1: 97-104.).

The skin condition improvement may include wrinkle improvement, skin aging prevention, and prevention or improvement of skin elasticity reduction, but is not limited thereto. The term "wrinkle improvement" of the present invention means maintaining or enhancing wrinkles and elasticity of the skin. The term "prevention of skin aging" of the present invention refers to both preventing or delaying chronological aging (endogenous aging), which is natural aging caused by physiological changes in the body over time, and photoaging (photoinduced aging) occurring in areas exposed to sunlight.

It has been reported that advanced glycation end products increase during the skin aging process and that glycation reaction is further increased in photoaged skin (JEANMAIRE, C, et al. British Journal of Dermatology , 2001, 145.1: 10-18.), and advanced glycation end products generated due to the glycation reaction of proteins present in the skin have been reported to cause decreased cell regeneration, reduced skin contraction function, reduced elasticity, and reduced tissue permeability (GKOGKOL OU, Paraskevi; BΦHM, Markus. Dermato-endocrinology , 2012, 4.3: 259-270.).

The term "prevention" of the present invention refers to all activities of suppressing or delaying advanced glycation end-related diseases by administering the pharmaceutical composition of the present invention to a subject.

The term "improvement" as used herein refers to any activity that improves or benefits advanced glycation end products-related diseases, cholesterol level, joint or bone health, or skin condition by using the compound according to one embodiment of the present invention.

The food composition of the present invention may contain the compound in various amounts as long as it has an active effect of reducing advanced glycation end products.

In the present invention, the compound according to one embodiment of the present invention may have an activity for reducing advanced glycation end products.

Advanced glycation products cause abnormal physicochemical changes in the structure of the body and other protein connective tissues, leading to metabolic diseases, diabetic complications, Alzheimer's disease, kidney disease, heart disease, vascular disease, aging, uremia, cataract, Parkinson's, or cancer. It is known to cause diseases. Therefore, the compound of the present invention having an activity of reducing advanced glycation end products can be used for preventing or treating these diseases.

Since the "food" composition of the present invention can be consumed on a daily basis, the effect of reducing advanced glycation end products in the body through reduction of the degradation of advanced glycation end products and the effect of preventing or improving advanced glycation end products related diseases can be expected, which is very useful.

As another aspect for achieving the above object, the present invention provides a food additive composition comprising a compound according to an embodiment of the present invention as an active ingredient.

The food additive composition according to the present invention is a food additive derived from natural materials, is safe to the human body, and can replace conventional synthetic food preservatives.

Food additives are used for a special purpose in processed foods, and each additive has a specific purpose. Additives used during manufacturing and processing of food are usually used for multiple purposes rather than for one specific purpose.

The natural food additive composition of the present invention may be characterized by activating the reduction (decomposition) of advanced glycation end products.

According to one embodiment, the natural food additive composition may include the compound alone, and may further include other pharmacologically acceptable substances. The pharmacologically acceptable substance may be an antibacterial or bactericidal agent, and may be a diluent or excipient.

Examples of the antibacterial agent include proteins such as lysozyme, polylysine, protamine, conalbumin, and avidin, organic acids such as acetic acid, banzoic acid, aleic acid, and succinic acid, pectin decomposition products, browning reactants, lower fatty acid esters, or spices.

As another aspect for achieving the above object, the present invention provides a feed composition having final glycation end product 　reduction 　activity, containing the compound according to an embodiment of the present invention as an active ingredient.

In the present invention, the term "feed" may mean any natural or artificial diet, one meal, etc., or a component of the one meal meal, for or suitable for animals to eat, ingest, and digest.

The type of feed is not particularly limited, and feeds commonly used in the art may be used. The feed composition may include a feed additive. The feed additive of the present application corresponds to supplementary feed under the Feed Management Act, and may include probiotics. Non-limiting examples of the feed include vegetable feeds such as grains, root fruits, food processing by-products, algae, fibers, pharmaceutical by-products, oils and fats, starches, meal or grain by-products; Animal feed such as proteins, inorganic materials, oils, mineral oils, oils, single cell proteins, zooplankton, or food may be mentioned. These may be used alone or in combination of two or more.

At this time, the feed composition containing the compound according to an embodiment of the present invention as an active ingredient may further include an excipient, a diluent, and an additive.

As another aspect for achieving the above object, the present invention provides a pharmaceutical composition for preventing or treating advanced glycation end products-related diseases, comprising the compound according to one embodiment of the present invention as an active ingredient.

The term "treatment" of the present invention refers to all activities that improve or alleviate advanced glycation end-related diseases or benefit from the administration of the pharmaceutical composition of the present invention to a subject.

The pharmaceutical composition of the present invention may further include a pharmaceutically acceptable carrier, excipient or diluent according to conventional methods. Pharmaceutically acceptable carriers are well known in the art depending on the route of administration or dosage form, and specific reference may be made to the pharmacopoeia of each country including the 'Korean Pharmacopoeia'. Carriers, excipients and diluents that may be included in the composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, and talc. , magnesium stearate and mineral oil, but are not limited thereto. In addition, carriers, excipients and diluents that may be included in the composition of the present invention may be non-natural carriers, but are not limited thereto.

The pharmaceutical composition of the present invention may be formulated and used in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories or sterile injection solutions according to conventional methods. Specifically, when formulated, it may be prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and such solid preparations may be prepared by mixing the compound with at least one excipient, for example, starch, calcium carbonate, sucrose, lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid formulations for oral administration include suspensions, internal solutions, emulsions, syrups, etc., and various excipients such as wetting agents, sweeteners, aromatics, preservatives, etc. may be included in addition to water and liquid paraffin, which are commonly used simple diluents. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried formulations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents. As a base for the suppository, Witepsol, Macrogol, Tween 61, cacao butter, laurin paper, glycerogelatin, and the like may be used. The specific formulation of the pharmaceutical composition is known in the art, and reference may be made to, for example, Remington's Pharmaceutical Sciences (19th ed., 1995). These documents are considered as part of this specification.

The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. The pharmacologically effective amount means an amount that is sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment and does not cause side effects, and the effective dose level may be determined according to the patient's state of health, type of disease, severity, drug activity, drug sensitivity, administration method, administration time, administration route and excretion rate, treatment period, combination or simultaneous use of drugs, and other factors well known in the medical field. The dosage and frequency do not limit the scope of the present invention in any way.

The pharmaceutical composition of the present invention may be administered to mammals such as mice, dogs, cats, cows, horses, pigs, and humans through various routes, and may be preferably human. Any mode of administration may be expected, and may be administered by, for example, oral, intravenous, intramuscular or subcutaneous injection, but is not limited thereto.

As another aspect for achieving the above object, the present invention provides a method for preparing a compound according to an embodiment of the present invention comprising the following steps:

(1) mixing psicose with an aqueous hydrochloric acid solution and inducing caramelization;

Mix psicose powder and hydrochloric acid (cooled to 4 degrees) at a ratio of 1:10 (w/v). The mixed solution is reacted for about 3 days or more.

(2) neutralizing the reactants after step (1);

According to one embodiment, the reactants may be neutralized using an ion exchange column. For example, a reactant is placed in a glass column filled with an ion exchange resin (eg, DEAE Sepharose Fast Flow - weak anion exchange chromatography resin) and neutralized with a 2M NaOH aqueous solution.

(3) enzymatically reacting the reactants after step (2) using a polymerase;

Enzymes (ex, EC 3.2.1.134, EC 4.2.2.16, EC 4.2.2.17, EC 4.2.2.18, EC 5.1.3.30) are added to the reaction obtained in step (2) and incubated at 30-50 degrees and 400 RPM for 1-6 days.

(4) Filtering the reactants after step (3) and purifying dipsicose dianhydride.

The reaction product obtained in step (2) is centrifuged and the enzyme is removed with a filter paper. The purified reactant is separated into a single composition under 80% acetonitrile conditions using a preparative liquid chromatography instrument equipped with a C ₁₈ column treated with NH ₂ functional groups. Thereafter, dipsicose dianhydride (DPA) is obtained through a process of concentration under reduced pressure and freeze-drying.

The psicose-derived compound according to the present invention is non-toxic to cells and has an effect of reducing cytotoxicity caused by advanced glycation end products.

In addition, the psicose-derived compound can be usefully used in various industries such as food and medicine to prevent, improve, or treat various diseases that may be caused by advanced glycation end products.

However, effects that can be achieved by the psicose-derived compound according to an embodiment of the present invention are not limited to those mentioned above, and other effects not mentioned will be clearly understood by those skilled in the art from the description below.

In order to more fully understand the drawings cited in the present invention, a brief description of each drawing is provided.
1 is a flowchart schematically illustrating a process for preparing a psicose-derived compound according to an embodiment of the present invention.
Figure 2 (a) is the result of confirming the components included in the reactant (A) produced by the polymerase with a refractive index detector (RI) using a high-performance liquid chromatography (HPLC) device. Figure 2 (b) shows that the psicose-derived compound according to an embodiment of the present invention is included in the enzyme reactant.
3 is a result of measuring the molecular weight of a psicose-derived compound according to an embodiment of the present invention by high resolution mass spectrometry (HRMS).
4 is a nuclear magnetic resonance (NMR) measurement result to confirm the binding method and molecular structure of the psicose-derived compound according to an embodiment of the present invention. 1H-NMR (A), 13C-NMR (B), HSQC-NMR (C), DEPT-NMR (D), COSY-NMR (E), HMBC-NMR (F), NOESY-NMR (G), ROSEY-NMR (H).
5 shows a molecular structure of a psicose-derived compound according to an embodiment of the present invention.
6 is a measurement result of calorimetric characteristics of psicose (A) and psicose-derived compound (B) according to an embodiment of the present invention using a differential scanning calorimeter (DSC).
7 is a result showing the ratio of apoptotic cells compared to a control group when kidney glomerular cell lines were treated with a representative terminal glycation end product (methylglyoxal) and a psicose-derived compound according to an embodiment of the present invention.

Hereinafter, the configuration and effects of the present invention will be described in more detail through examples. These examples are only for illustrating the present invention, and the scope of the present invention is not limited thereto.

<Example>

Example 1. Preparation of dipsicose dianhydride (DPA)

1 is a flow chart briefly illustrating a process for preparing dipsicose dianhydride (DPA) having a characteristic of reducing advanced glycation end products using psicose powder.

(1) Caramelization of psicose under strong acid conditions

Psicose powder is dissolved in strong acid conditions to generate radicals.

As the strong acid condition, hydrochloric acid stock solution (about 12.3M) was used. The psicose powder is dissolved in a stock solution of hydrochloric acid at a ratio of 1 g / 1 mL to generate radicals.

(2) Neutralization

The psicose solution is neutralized using an ion exchange column.

A reactant was put into a glass column filled with ion exchange resin and neutralized with 1M NaOH aqueous solution.

(3) polymerization

Polymerize under neutral conditions using enzymes (EC 4.2.2.18, EC 2.4.1, EC 2.4.1.10).

(4) Separation and purification

Enzymes and impurities are removed from the reaction solution, and a single component of dipsicose dianhydride (DPA) is obtained using preparative high-performance liquid chromatography.

Figure 2 (a) is the result of confirming the components included in the reactant (A) produced by the polymerase with a refractive index detector (RI) using a high-performance liquid chromatography (HPLC) device. Referring to FIG. 2 (b), it can be seen that three or more components were produced, and among them, the target material (B) confirmed by separation and purification was included in the enzyme reaction product.

(5) structure identification

The molecular weight is determined with a high-resolution mass spectrometer, and the binding method and molecular structure are determined with a nuclear magnetic resonance device.

Figure 3 is the result of measuring the molecular weight of the single component of DPA separated and purified by high resolution mass spectrometry (HRMS). Referring to FIG. 3 , 347.0952 m/z is obtained by combining Na(23 m/z ) with 324.1056 m/z calculated from the molecular formula C ₁₂ H ₂₀ O ₁₀ .

Example 2. Measurement of DPA physicochemical properties

Differences in physicochemical properties from psicose were confirmed using differential scanning calorimetry.

6 is a result of measuring calorimetric characteristics of psicose and DPA according to the above example using a differential scanning calorimeter (DSC). Psicose (A) has a maximum value at 126.5 degrees, whereas DPA (B) has a higher thermal stability at 194.7 degrees.

<Experimental example>

Experimental Example 1. Evaluation of advanced glycation end product inhibition efficacy

Whether treatment of DPA to renal glomerular cells exposed to advanced glycation end products improved cell viability was evaluated. In addition, the cytotoxicity of DPA was evaluated.

7 is a result showing the ratio of apoptotic cells compared to the control group when kidney glomerular cell lines were treated with methylglyoxal and DPA according to the above example. The group treated with advanced glycation end products (red bars) shows that 50% of the cells are killed compared to the control group (black bars). On the other hand, when the same molar concentration of DPA is treated with advanced glycation end products (light green bar), it indicates that less than 10% of cells are killed. When the kidney glomerular cell line was treated with only DPA (blue bar), the degree of cell death was the same as that of the control group, indicating that DPA is not toxic. The presented experimental results were measured more than three times, and statistical significance was verified through one-way ANOVA.

<Formulation example>

1. Preparation of powder

Dipsicose dianhydride (DPA) 500 mg

Lactose 100 mg

Talc 10 mg

A powder is prepared by mixing the above ingredients and filling them in an airtight bag.

2. Preparation of tablets

DPA 500mg

Corn Starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

After mixing the above ingredients, tablets are prepared by tableting according to a conventional tablet manufacturing method.

3. Preparation of capsules

DPA 500mg

Corn Starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

Capsules are prepared by mixing the above ingredients and filling them into gelatin capsules according to a conventional capsule preparation method.

4. Preparation of liquid formulations

DPA 10mg

Isomerized sugar 10 g

5 g mannitol

Appropriate amount of purified water

According to the conventional method for preparing liquids, each component is dissolved in purified water, lemon flavor is added in an appropriate amount, the above components are mixed, and then purified water is added to adjust the total volume to 100 ml, and then filled into a brown bottle to sterilize to prepare a liquid.

Although the present invention has been described in detail above, the scope of the present invention is not limited thereto, and various modifications and variations are possible without departing from the technical spirit of the present invention described in the claims. It will be apparent to those skilled in the art.

Claims (19)

As a dipsicose dianhydride compound,
The compound is represented by Formula 2 below.
[Formula 2]

delete delete delete delete delete According to claim 1,
The compound having the activity of reducing the final glycation end products, the compound. A pharmaceutical composition for preventing or treating diabetic nephropathy, diabetic retinopathy or diabetic neuropathy, comprising the compound of claim 1 as an active ingredient. delete delete delete delete delete A food composition containing the compound of claim 1 as an active ingredient and having final glycation end product 　reduction 　activity. A food composition for improving diabetic nephropathy, diabetic retinopathy or diabetic neuropathy, comprising the compound of claim 1 as an active ingredient. Claim 14 comprising a food composition, diabetic nephropathy, diabetic retinopathy or diabetic neuropathy for improving health functional food. A feed composition containing the compound of claim 1 as an active ingredient and having final glycation end product reduction activity. A composition for food additives containing the compound of claim 1 as an active ingredient and having an activity of reducing final glycated products. A method for preparing a dipsicose dianhydride compound, comprising the following steps:
(1) mixing psicose with an aqueous hydrochloric acid solution and inducing caramelization;
(2) neutralizing the reactants after step (1);
(3) enzymatically reacting the reactants after step (2) using a polymerase;
(4) Filtering the reactants after step (3) and purifying dipsicose dianhydride.