Anti-glycation agents

Abstract

To provide an anti-glycation agent and a composition with significantly improved anti-glycation action.SOLUTION: A research on the effects of iron compounds on the formation of glycation products has yielded surprising findings: the iron compounds possess anti-glycation action. According to the discovery, blending the iron compounds with a specific material leads to a dramatic increase in anti-glycation action. Specifically, the present invention discloses (1) anti-glycation agents including iron compounds, (2) compositions including iron compounds and lemon balm, and (3) anti-glycation agents including iron compounds and lemon balm.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to an anti-glycation agent.

Background Art

[0002] The Maillard reaction is known as a typical non-enzymatic reaction that occurs when reducing sugars and amino compounds (amino acids, proteins, etc.) coexist. In the food field, while it contributes to enhancing added value by being involved in baked color and aroma, this reaction also occurs during the storage of foods without heat cooking, and thus it has become one of the causes of quality degradation for foods that emphasize the color and aroma of raw materials and immediately after cooking and processing.

[0003] It is also known that in vivo, glycation occurs in various proteins through non-enzymatic chemical reactions between amino acids, proteins, and reducing sugars. Glycated proteins reach advanced glycation end products (AGEs) through glycation reaction intermediates centered on carbonyl compounds. Some AGEs involve crosslink formation. Therefore, glycation stress causes physiological and physical damage to various tissues and cells. Furthermore, it is known that AGEs bind to its receptor RAGE (receptor for AGEs) and cause inflammation through intracellular signal transduction.

[0004] Glycation stress is one of the risk factors for aging. The pathological condition in which its effect appears most prominently is diabetes, and in the three major complications of diabetes, neuropathy, retinopathy, and nephropathy, a large amount of AGEs accumulates in tissues. In addition, the generation and accumulation of AGEs due to glycation are involved not only in diabetic complications but also in the progression of skin aging, dementia, hypertension, arteriosclerosis, osteoporosis, etc. that increase with aging, and the effect of reducing AGEs generation is considered to lead to anti-aging. Therefore, in the fields of cosmetics and health foods, materials, products, and services with the keyword "anti-glycation" have attracted attention. To date, it has been discovered that ethanol extracts from peony flowers have anti-glycation properties and have been reported to be effective for anti-aging (Patent Document 1).

[0005] On the other hand, minerals such as calcium, phosphorus, potassium, sodium, sulfur, magnesium, iron, copper, zinc, selenium, manganese, and iodine are well known, and along with proteins, carbohydrates, fats, and vitamins, they are one of the five major nutrients. They play important roles in the body, mainly as components of biological tissues (bones, teeth, etc.), maintaining homeostasis of body fluids (pH and osmotic pressure regulation, etc.), as cofactors for enzymes, regulating the excitability of nerves, muscles, and the heart, and as components of physiologically active substances.

[0006] In other words, daily intake of various minerals is essential for humans to maintain health. Iron deficiency, in particular, is well known to cause anemia. However, there has been little research on the effects of minerals, especially iron, on inhibiting the formation of advanced glycation end products (AGEs). [Prior art documents] [Non-patent literature]

[0007] [Non-Patent Document 1] Life Hygiene News, Shizuoka Environmental Testing Center Co., Ltd., 3(10), 2016 [Non-Patent Document 2] Yagi, Masayuki et al., Oleoscience, 18(2), 17-23, 2018. [Patent Documents]

[0008] [Patent Document 1] Japanese Patent Publication No. 2017-88553 [Overview of the project] [Problems that the invention aims to solve]

[0009] The object of the present invention is to provide an anti-glycation agent and a composition that significantly improves anti-glycation activity. [Means for solving the problem]

[0010] The inventors investigated the effect of iron compounds on the formation of glycated products and, surprisingly, discovered that iron compounds have anti-glycation properties. Furthermore, we discovered that by incorporating specific materials in addition to iron compounds, the anti-glycation effect is dramatically improved.

[0011] In other words, the present invention is as follows: (1) An anti-glycation agent containing an iron compound. (2) A composition containing an iron compound and lemon balm. (3) An anti-glycation agent containing iron compounds and lemon balm. [Effects of the Invention]

[0012] According to the present invention, an excellent anti-glycation agent can be obtained. Furthermore, by using the anti-glycation agent or composition of the present invention, glycation in the body can be prevented, and various symptoms and diseases caused by glycation can be prevented / treated. In addition, the glycation of amino acid compounds contained in compositions of food and beverages can be suppressed, and as a result, the quality of food and beverages can be kept stable. [Brief explanation of the drawing]

[0013] [Figure 1] Figure 1 is a graph showing the degree of saccharification of ammonium citrate in the examples. [Figure 2] Figure 2 is a graph showing the degree of glycation of ferric pyrophosphate in the examples. [Figure 3] Figure 3 is a graph showing the degree of saccharification of ammonium iron citrate and lemon balm in the examples. [Figure 4] Figure 4 is a graph showing the degree of saccharification of ferric pyrophosphate and lemon balm in the examples. [Modes for carrying out the invention]

[0014] The iron compounds of the present invention include, for example, ferrous fumarate, ferric chloride, iron citrate, ammonium iron citrate, sodium iron citrate, ferrous gluconate, iron lactate, ferrous pyrophosphate, ferric pyrophosphate, ferrous sulfate, heme iron, iron sesquioxide, and sodium iron chlorophyllin.

[0015] The lemon balm of the present invention is a crude drug or plant derived from the leaves of lemon balm (alias: Melissa, scientific name: Melissa officinalis) of the genus Melissa in the Lamiaceae family, and is used in the form of a crude drug powder or plant powder, a crude drug extract or a plant extract. The crude drug powder or plant powder used in the present invention may be, for example, a powdery dried product obtained by further finely pulverizing a dried cut product.

[0016] The lemon balm extract used in the present invention can be extracted with solvents such as water, lower aliphatic alcohols (such as methanol, ethanol, isopropyl alcohol), polyhydric alcohols (such as 1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin), lower aliphatic ketones (such as acetone), or a mixture of these solvents. Among these, it is most preferable to extract with water, lower aliphatic alcohols, polyhydric alcohols, or a mixture of these.

[0017] Also, the form of the extract is not particularly limited, and it can be made into a dried extract powder, an extract powder, a soft extract, a liquid extract, etc. by treatments such as heat treatment, freeze drying, vacuum drying, or powdering with an excipient such as dextrin. Commercially available products of lemon balm extract include "Lemon Balm Extract A", "Lemon Balm Extract Powder MF" of Maruzen Pharmaceutical Co., Ltd., and "Falcorex Melissa B" of Ichimaru Pharcos Co., Ltd.

[0018] Since the anti-glycation agent of the present invention has an excellent anti-glycation effect, it is suitable for blending into, for example, skin application preparations or oral compositions. Examples of the dosage forms of skin application preparations include lotions, creams, patches, sprays, gels, ointments, lotions, emulsions, beauty essences, and the like. These can be produced by known methods. Examples of the dosage forms of oral compositions include tablets, powders, powders, granules, liquids, capsules, dry syrups, jelly agents, liquid foods, semi-solid foods, solid foods, and the like. In the production, various additives that can be contained in quasi-drugs, pharmaceuticals, foods and drinks, reagents or cosmetics can be blended within a range that does not impair the effects of the present invention.

[0019] Preferably, it is applied to humans, but it can also be applied to animals other than humans as long as the action and effect are achieved. Further, since the anti-glycation agent of the present embodiment has an excellent anti-glycation effect, it can also be suitably used as a reagent for research related to the glycation reaction, for example, research related to the formation mechanism of AGEs or the decomposition mechanism of AGEs.

[0020] Since the composition of the present invention has an anti-glycation effect, it can be used for the purpose of preventing / treating various symptoms caused by glycation. Examples of such symptoms include aging, diabetes and its complications, osteoporosis, Alzheimer's dementia, hyperlipidemia, arteriosclerosis, hypertension, obesity, skin wrinkles, skin spots, skin sagging, decreased skin elasticity, skin dullness, cataract, and the like. Therefore, the composition of the present invention can be used as an anti-glycation composition, an anti-aging composition, or a beauty composition. Further, by using the present invention, the glycation reaction in the composition of foods and drinks can be suppressed, and a product with high quality stability can be provided.

[0021] The blending amount of the iron compound in the composition of the present invention is not particularly limited, but when provided as a cosmetic, quasi-drug, pharmaceutical, food and drink, or reagent, it is 0.000001 to 10% by mass, preferably 0.0001 to 5% by mass, more preferably 0.001 to 1% by mass, based on the whole composition, respectively. Furthermore, while the amount of lemon balm in the composition of the present invention is not particularly limited, when provided as a cosmetic, quasi-drug, pharmaceutical, food or beverage, or reagent, it is preferably 0.000001 to 10% by mass, more preferably 0.0001 to 5% by mass, and more preferably 0.001 to 1% by mass, relative to the total composition.

[0022] The anti-glycation agent and its instructions of the present invention may bear a statement indicating that it is used for anti-glycation effects. Here, "bearing a statement" includes including it on the main body, container, packaging, etc. of the product containing the anti-glycation agent, or including it in documents such as instructions, accompanying documents, brochures, and other printed materials that disclose product information, and including it in various leaflets and advertisements used for promotion, including on the internet. Furthermore, products that indicate they have other functions, or products that do not indicate functions but substantially possess anti-glycation effects, are also included within the scope of the present invention. [Examples]

[0023] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0024] <Testing Method> The neutralized collagen solution was cooled on ice and dispensed into a 96-well plate (black plate) at a rate of 50 μL per well. The lidded 96-well plate was placed over the plate and left to stand overnight in a humid 37°C incubator. 40 μL of the test substance, dissolved to an appropriate concentration in buffer solution, was added onto the collagen gel. 10 μL of 500 mM glyceraldehyde solution was added to each well, and the plate was mixed with a plate mixer. Within 5 minutes of adding the glyceraldehyde solution, the fluorescence intensity at an excitation wavelength of 370 nm and an emission wavelength of 440 nm was measured using a fluorescence plate reader (fluorescence intensity A). After standing for 24 hours in a humid 37°C incubator, the fluorescence intensity at an excitation wavelength of 370 nm and an emission wavelength of 440 nm was measured again using a fluorescence plate reader (fluorescence intensity B), and the glycation degree of each well was calculated by subtracting fluorescence intensity A from fluorescence intensity B.

[0025] The following substances were used as test materials. • As iron compounds, ammonium iron citrate and ferric pyrophosphate • Lemon balm: Powdered hot water extract of lemon balm leaves and stems (commercially available) <Test Results> Figures 1 and 2 show that the iron compounds reduced the degree of glycation in a concentration-dependent manner. Figures 3-4 show that lemon balm did not exhibit anti-glycation effects, but when used in combination with iron compounds, it significantly enhanced the anti-glycation effects of the iron compounds. [Industrial applicability]

[0026] Because the composition of the present invention has anti-glycation properties, it can be used in the fields of quasi-drugs, pharmaceuticals, food and beverages, or cosmetics.

Claims

1. An anti-glycation agent containing ammonium iron citrate or ferric pyrophosphate.

2. An anti-glycation agent containing ammonium iron citrate or ferric pyrophosphate and lemon balm.

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