Advanced glycation end products (AGEs) decomposition promoter

Extracts from Ononis, Kujin, Emmeisou, and Moon Peach are processed to create anti-saccharides that inhibit or promote AGES formation/decomposition, addressing diabetes, arteriosclerosis, osteoporosis, and skin issues, providing effective treatments.

JP7624190B2Active Publication Date: 2025-01-30MARUZEN PHARMA
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Patent Information

Application Number
JP2020119328
Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
Filing Date
2020-07-10
Publication Date
2025-01-30
Estimated Expiration
2040-07-10

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Abstract

To provide an anti-glycation agent having excellent anti-glycation action.SOLUTION: An anti-glycation agent contains as an active ingredient one or more extracts selected from the group consisting of Ononis spinosa L. extract, Sophora root extract, Golden Silk extract, Isodon Japonicas extract, Sanguisorba officinalis extract, Alpinia speciosa extract and Rubus ellipticus Smith extract.SELECTED DRAWING: None
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Description

[Technical field]

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

[0002] Carbohydrates are extremely important as an energy source for humans and other living organisms. However, it is known that carbohydrates undergo glycation reactions with proteins. Glycation is a series of reactions that begin with a nonenzymatic reaction between the carbonyl group of carbohydrates and the amino group of proteins, etc., and then proceeds through Schiff bases and Amadori compounds to finally form advanced glycation end products (hereinafter sometimes referred to as "AGEs"). Glycation nonenzymatically modifies proteins with sugars, which causes the denaturation of the proteins and cross-linking between proteins, resulting in a decrease in protein function.

[0003] Glycation not only causes direct damage by modifying and structurally changing proteins that constitute the extracellular matrix, such as collagen, but also induces cellular responses by being recognized by receptors that use glycated proteins as ligands. The impact of glycation is particularly severe for diabetic patients, who have high glucose levels in the blood. It is known that protein glycation is one of the causes of diabetic complications, such as diabetic neuropathy, diabetic retinopathy, and diabetic nephropathy. It is also known that glycation in the vascular wall leads to the progression of arteriosclerosis through endothelial cell damage and accumulation of denatured proteins.

[0004] Furthermore, extracellular matrix components such as collagen account for more than half of the dry weight of tissues such as bones and skin. Therefore, for example, when collagen is glycated and abnormally cross-linked, it can cause osteoporosis, osteoarthritis, etc. in bone and cartilage tissues, and cause a decrease in elasticity and dullness due to yellowing, etc. in the skin. Furthermore, abnormally cross-linked collagen, etc., is less susceptible to degradation by collagenase, etc., and this can lead to problems such as the induction of collagenase, etc., leading to the degradation of normal collagen as well.

[0005] Therefore, if it were possible to somehow inhibit glycation reactions, i.e., inhibit the formation of AGEs or promote the decomposition of AGEs, it would be expected to be useful in preventing or treating the above-mentioned diseases, i.e., diabetic complications, arteriosclerosis, osteoporosis, osteoarthritis, etc. Furthermore, it is expected to be effective in preventing or improving loss of elasticity and dullness of the skin.

[0006] Conventionally, N-phenacylthiazolium bromide has been known as a compound having anti-glycation activity (Non-Patent Document 1). However, this compound has safety issues and is not suitable as a medicine or topical skin agent. In addition, as a component derived from a natural product having anti-glycation activity, for example, an extract from mugwort is known (Patent Document 1). However, it is difficult to say that there is a sufficient supply of substances having anti-glycation activity, and there is a strong demand for the development and supply of further new substances having anti-glycation activity. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] JP 2001-122758 A [Non-patent literature]

[0008] [Non-Patent Document 1] Vasan S. et al.,Nature,July 18, 1996,Vol. 82,No. 6588,p.275-278 Summary of the Invention [Problem to be solved by the invention]

[0009] An object of the present invention is to provide an anti-glycation agent having excellent anti-glycation activity. [Means for solving the problem]

[0010] In order to solve the above problems, the anti-glycation agent of the present invention is an extract of Ononis, an extract of Sophora root, an extract of Golden silk, an extract of Enmeiso, an extract of Sanguinea japonica, and an extract of Shell Ginger. Things The present invention is characterized in that it contains, as an active ingredient, one or more extracts selected from the group consisting of:

[0011] In the above invention (Invention 1), it is preferable that one or more extracts selected from the group consisting of Ononis extract, Sophora root extract, Golden silk extract, Enmeiso extract and Sanguisorba officinalis extract are used for inhibiting the formation of advanced glycation end products (AGEs) (Invention 2).

[0012] In the above invention (Invention 1), shell ginger extract Things It is preferable that the composition is used for promoting the decomposition of advanced glycation end products (AGEs) (Invention 3). Effect of the Invention

[0013] According to the present invention, an anti-glycation agent having excellent anti-glycation effect can be provided. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] Hereinafter, an embodiment of the present invention will be described. The anti-glycation agent of the present embodiment is an extract of Ononis, an extract of Sophora root, an extract of Golden silk, an extract of Enmeiso, an extract of Sanguinea japonica, and an extract of Shell Ginger. Things The present invention relates to an extract comprising one or more active ingredients selected from the group consisting of:

[0015] Here, in this embodiment, "extract" includes extracts and hydrolyzed solutions obtained using Ononis, Sophora Root, Golden Silk, Enmeisou, Sanguinea Pyrola, or Shell Ginger as raw materials, diluted or concentrated solutions of the extracts and hydrolyzed solutions, dried products obtained by drying the extracts and hydrolyzed solutions, or crude or purified products thereof.

[0016] Ononis (scientific name: Ononis spinosa L.) is a semi-shrub of the genus Ononis in the family Fabaceae, widely distributed in Asia and Europe, and can be easily obtained from these regions. The constituent parts of Ononis that can be used as the extraction raw material include, for example, above-ground parts such as leaves, stems, and flowers, underground parts such as rhizomes and roots, seeds, the whole plant, or a mixture of these parts, and preferably the roots.

[0017] Sophora flavescens Aiton (herbal medicine name) is the root of the perennial herb Sophora flavescens (scientific name: Sophora flavescens Aiton), which belongs to the genus Sophora and is distributed throughout Japan, Korea, and China, and can be easily obtained from these areas. Sophora flavescens has traditionally been used as a stomachic, diuretic, antipyretic, and analgesic drug.

[0018] Enmeisou (herbal medicine name) is the whole plant of Isodon japonica, a perennial plant belonging to the mint family, distributed from Hokkaido to Shikoku and Kyushu, and can be easily obtained in these areas. Enmeisou has traditionally been used as a bitter stomachic, stomach spasm reliever, indigestion reliever, etc.

[0019] Sanguisorba officinalis (scientific name: Sanguisorba officinalis) is a plant of the Rosaceae family, distributed from Hokkaido to Kyushu, and from China to Siberia and Europe, and is easily available in these areas. There are no particular restrictions on the parts that can be used as raw materials for extraction, and they can be selected appropriately depending on the purpose, but examples include leaves, branches, stems, flowers, buds, fruits, roots, rhizomes, above-ground parts, and mixtures of these. Among these, roots and rhizomes are preferred, and are called jiu in herbal medicine.

[0020] Shell ginger (scientific name: Alpinia speciosa (Wendl.) K. Schum.) is a perennial evergreen herb belonging to the genus Alpinia in the family Zingiberaceae, and is distributed from southern Kyushu to India, and can be easily obtained from these regions. Shell ginger is called sannin in Okinawa, and is used in muchi, a traditional sweet since the Ryukyu Dynasty, as well as being used as an herb. Parts that can be used as the raw material for extraction include, for example, leaves, trunks, above-ground parts, flowers, fruits, seeds, roots, the whole plant, or a mixture of these parts, with the leaves being preferred.

[0021] Ononis, Kujin, Enmeisou, Waremokou or Moon Peach The extract can be obtained by drying the extraction raw material, pulverizing it using a crusher, and then subjecting it to extraction with an extraction solvent. The drying can be done in the sun or using a commonly used dryer. The raw material can also be used after pretreatment such as degreasing with a non-polar solvent such as hexane. By performing pretreatment such as degreasing, the extraction process of the raw material can be efficiently performed with a polar solvent.

[0022] As the extraction solvent, it is preferable to use a polar solvent, such as water or a hydrophilic organic solvent, which is preferably used alone or in combination of two or more at room temperature or at a temperature below the boiling point of the solvent.

[0023] Water that can be used as an extraction solvent includes pure water, tap water, well water, mineral water, hot spring water, spring water, fresh water, etc., as well as water that has been subjected to various treatments. Treatments that can be applied to water include, for example, purification, heating, sterilization, filtration, ion exchange, osmotic pressure adjustment, buffering, etc. Therefore, water that can be used as an extraction solvent in this embodiment also includes purified water, hot water, ion-exchanged water, physiological saline, phosphate buffer, phosphate buffered physiological saline, etc.

[0024] Examples of hydrophilic organic solvents that can be used as the extraction solvent include lower aliphatic alcohols having 1 to 5 carbon atoms, such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; lower aliphatic ketones, such as acetone and methyl ethyl ketone; and polyhydric alcohols having 2 to 5 carbon atoms, such as 1,3-butylene glycol, propylene glycol, and glycerin.

[0025] When a mixture of two or more polar solvents is used as an extraction solvent, the mixing ratio can be adjusted appropriately. For example, when a mixture of water and a lower aliphatic alcohol is used as an extraction solvent, the mixing ratio of water to lower aliphatic alcohol is preferably 9:1 to 1:9 (volume ratio), more preferably 7:3 to 1:9 (volume ratio). When a mixture of water and a lower aliphatic ketone is used, the mixing ratio of water to lower aliphatic ketone is preferably 9:1 to 2:8 (volume ratio), and when a mixture of water and a polyhydric alcohol is used, the mixing ratio of water to polyhydric alcohol is preferably 8:2 to 1:9 (volume ratio).

[0026] The extraction process is not particularly limited as long as the soluble components contained in the extraction raw material can be dissolved in the extraction solvent, and can be performed according to a conventional method. For example, the extraction raw material is immersed in an extraction solvent of 5 to 50 times the amount (mass ratio) of the extraction raw material, and the soluble components are extracted at room temperature or under reflux heating, and then the extraction residue is removed by filtration to obtain an extract. The solvent is distilled off from the obtained extract to obtain a paste-like concentrate, and the concentrate is further dried to obtain a dry product.

[0027] The extract obtained as described above can be used as it is as an active ingredient of an anti-glycation agent, but it is easier to use it in the form of a concentrated liquid or a dried product.

[0028] Also, ononis extract, lycium rhizome extract, enmeisou extract, sanguisorba officinalis extract and shell ginger extract ThingsBecause it has a unique odor, it is possible to purify it for the purposes of decolorization, deodorization, etc., to the extent that this does not result in a decrease in its physiological activity; however, since it is not used in large quantities when incorporated into topical skin preparations, etc., there is no practical problem with leaving it unpurified.

[0029] The golden silk extract in this embodiment is obtained by hydrolyzing golden silk using an aqueous acid or alkali solution.

[0030] Golden Silk is a deep yellow silk thread produced by the silkworm moth Bonbix mori. It is a special golden cocoon produced mainly in the Thunghuachang region of Lamphun Province, Thailand, and is also commercially available.

[0031] Acids that can be used in the hydrolysis treatment of golden silk include, for example, hydrochloric acid, sulfuric acid, etc., and one of these may be used alone or the two may be used in combination.

[0032] In addition, examples of alkali that can be used in the hydrolysis treatment of golden silk include sodium hydroxide, potassium hydroxide, etc., and one of these may be used alone or the two may be used in combination.

[0033] When hydrolysis is performed using an aqueous solution of acid or alkali, the amount of the aqueous solution of acid or alkali added and the concentration of the acid or alkali in the aqueous solution may be any amount that is capable of hydrolyzing golden silk, and the amount of the aqueous solution added and the concentration of the acid or alkali in the aqueous solution can be appropriately changed depending on the type of acid or alkali used, etc.

[0034] The hydrolysis treatment is carried out at a temperature of 0 to 130° C., preferably 50 to 120° C., for about 30 minutes to 10 days, preferably 1 hour to 5 days.

[0035] In this way, the solution obtained by the hydrolysis treatment is subjected to removal of acid or alkali, and if necessary, subjected to ultrafiltration treatment to remove high molecular weight peptides, and then subjected to further treatments such as concentration and drying to obtain a golden silk extract.

[0036] The acid or alkali can be removed from the solution obtained by hydrolysis by a conventional method, for example, freeze-drying or a method of neutralizing the acid or alkali in the solution to desalt it.

[0037] The thus obtained Ononis extract, Sophora root extract, Golden silk extract, Enmeiso extract, Sanguinea japonica extract and Shell Ginger extract Things Since it has an excellent anti-glycation effect, it can be used as an active ingredient of an anti-glycation agent. The anti-glycation agent of the present embodiment can be used for a wide range of applications such as medicines, quasi-drugs, cosmetics, and food and beverages.

[0038] Here, the anti-glycation effect of Ononis extract, Sophora root extract, Golden silk extract, Enmeisou extract, and Sanguisorba officinalis extract is preferably exerted based on the inhibitory effect on the formation of advanced glycation end products (AGEs), however, the anti-glycation effect of Ononis extract, Sophora root extract, Golden silk extract, Enmeisou extract, and Sanguisorba officinalis extract is not limited to the anti-glycation effect exerted based on the above-mentioned effect.

[0039] Furthermore, one or more extracts selected from the group consisting of Ononis extract, Sophora root extract, Golden silk extract, Enmeiso extract, and Sanguisorba officinalis extract can be used for inhibiting AGE formation by utilizing their AGE formation inhibitory effect. In other words, the anti-glycation agent of this embodiment can also be used as an AGE formation inhibitor containing the above extract as an active ingredient.

[0040] Shell ginger extract Things The anti-glycation effect is preferably exerted based on the decomposition promoting effect of advanced glycation end products (AGEs). ThingsThe anti-glycation effect is not limited to the anti-glycation effect exerted based on the above-mentioned action.

[0041] Also, shell ginger extract Things By utilizing the AGE decomposition-promoting effect, the anti-glycation agent of this embodiment can be used for promoting the decomposition of AGEs. That is, the anti-glycation agent of this embodiment can also be used as an AGE decomposition-promoting agent containing the above extract as an active ingredient.

[0042] In addition, Ononis extract, Sophora root extract, Golden silk extract, Enmeisou extract, Sanguinea oleracea extract and Shell ginger extract Things One or more extracts selected from the group consisting of may be used as an active ingredient in an agent for preventing and treating diabetic complications such as diabetic neuropathy, diabetic retinopathy, and diabetic nephropathy; arteriosclerosis caused by protein glycation; and osteoporosis and osteoarthritis caused by protein glycation, by utilizing their AGE formation inhibitory effect or AGE decomposition promoting effect, and may also be used as an active ingredient in an agent for preventing and improving reduced skin elasticity, dullness, and the like caused by protein glycation.

[0043] The anti-glycation agent of the present embodiment is an extract of Ononis, an extract of Sophora root, an extract of Golden silk, an extract of Enmeiso, an extract of Sanguinea japonica, an extract of Shell Ginger, Things It may consist of only these mixtures, or may be selected from the group consisting of Ononis extract, Sophora root extract, Golden silk extract, Enmeisou extract, Waremoco extract, and Shell Ginger extract. Things Or a mixture of these may be prepared.

[0044] The anti-glycation agent of the present embodiment can be formulated into any dosage form, such as powder, granules, tablets, liquid, etc., in accordance with a conventional method using a pharma- ceutically acceptable carrier such as dextrin, cyclodextrin, or any other auxiliary agent. In this case, examples of auxiliary agents that can be used include excipients, binders, disintegrants, lubricants, stabilizers, flavorings, and odorants. The anti-glycation agent can be used by being blended with other compositions (e.g., skin topical agents, oral compositions, etc.), and can also be used as ointments, topical liquid agents, patches, etc.

[0045] When the anti-glycation agent of this embodiment is formulated, it is possible to use an extract of Ononis, an extract of Sophora root, an extract of Golden silk, an extract of Enmeiso, an extract of Sanguinea japonica, an extract of Shell Ginger, Things The content of these mixtures is not particularly limited and can be appropriately set depending on the purpose.

[0046] In addition, the anti-glycation agent of the present embodiment may contain other natural extracts having an anti-glycation effect, such as Ononis extract, Sophora root extract, Golden silk extract, Enmeiso extract, Sanguinea japonica extract, Shell Ginger extract, etc., as necessary. Things Or a mixture of these can be used as an active ingredient.

[0047] Methods for administering the anti-glycation agent of this embodiment to a patient include transdermal administration and oral administration, and a method suitable for prevention, treatment, etc. may be appropriately selected depending on the type of disease.

[0048] Furthermore, the dosage of the anti-glycation agent of this embodiment may be appropriately increased or decreased depending on the type and severity of the disease, individual differences between patients, administration method, administration period, and the like.

[0049] The anti-glycation agent of the present embodiment is an extract of Ononis, an extract of Sophora root, an extract of Golden silk, an extract of Enmeiso, an extract of Sanguinea japonica, and an extract of Shell Ginger. ThingsThrough the anti-glycation effect of the anti-glycation agent, it is possible to prevent or treat diabetic complications such as diabetic neuropathy, diabetic retinopathy, and diabetic nephropathy, and also to prevent or treat arteriosclerosis caused by the glycation reaction of proteins. In addition, the anti-glycation agent of the present embodiment is an extract of Ononis, an extract of Sophora root, an extract of Golden silk, an extract of Enmeiso, an extract of Sanguinea japonica, and an extract of Shell Ginger. Things Through the anti-glycation effect of the anti-glycation agent, it is possible to prevent or improve loss of skin elasticity, dullness, etc., caused by protein glycation. Furthermore, the anti-glycation agent of the present embodiment can also prevent or treat diseases caused by protein glycation, such as osteoporosis and osteoarthritis. However, the anti-glycation agent of the present embodiment can be used for all applications in which it is meaningful to exert an anti-glycation effect, in addition to these applications.

[0050] When the anti-glycation agent of the present embodiment is used for inhibiting the formation of AGEs (when used as an AGE formation inhibitor), it can prevent or treat diabetic complications such as diabetic neuropathy, diabetic retinopathy, and diabetic nephropathy, prevent or treat arteriosclerosis caused by protein glycation, prevent or improve loss of elasticity and dullness of the skin caused by protein glycation, and prevent or treat diseases such as osteoporosis and osteoarthritis caused by protein glycation through the AGE formation inhibitory effect possessed by the Ononis extract, Sophora root extract, Golden silk extract, Enmeiso extract, and Sanguisorba officinalis extract. In particular, when the anti-glycation agent of the present embodiment is used for inhibiting the formation of AGEs (when used as an AGE formation inhibitor), it can be suitably used for preventing the above diseases. However, it can be used in all applications in which it is meaningful to exert an AGE formation inhibitory effect other than these applications.

[0051] When the anti-glycation agent of the present embodiment is used for promoting the decomposition of AGEs (when used as an AGE decomposition promoter), ThingsThrough the AGEs decomposition promoting effect possessed by the anti-glycation agent, it is possible to prevent or treat diabetic complications such as diabetic neuropathy, diabetic retinopathy, and diabetic nephropathy; prevent or treat arteriosclerosis caused by protein glycation; prevent or improve loss of skin elasticity and dullness caused by protein glycation; and prevent or treat diseases such as osteoporosis and osteoarthritis caused by protein glycation. In particular, when the anti-glycation agent of this embodiment is used for promoting the decomposition of AGEs (when used as an AGEs decomposition promoter), it can be suitably used for treating or improving the above-mentioned diseases. However, in addition to these uses, it can also be used for all uses in which it is meaningful to exert an AGEs decomposition promoting effect.

[0052] In addition, since the anti-glycation agent of the present embodiment has an excellent anti-glycation effect, it is suitable for incorporation into, for example, a skin external preparation or an oral composition. In this case, Ononis extract, Sophora root extract, Golden silk extract, Enmeisou extract, Sanguisorba officinalis extract, Shell Ginger extract Things Or a mixture of these may be used as is, or may be used in combination with Ononis extract, Sophora root extract, Golden silk extract, Enmeisou extract, Waremoco extract, Shell ginger extract Things Alternatively, the anti-glycation agent may be formulated from a mixture of these.

[0053] Here, topical skin preparations are not limited to specific classifications and include a wide range of skin cosmetics, quasi-drugs, medicines, etc. that are used percutaneously. Specific examples include ointments, creams, milky lotions, beauty serums, lotions, packs, foundations, lip balms, bath additives, hair tonics, hair lotions, soaps, body shampoos, etc.

[0054] Skin topicals: Ononis extract, Sophora root extract, Golden silk extract, Enmeisou extract, Sanguinea oleracea extract, Shell ginger extract Things The total amount of these mixtures can be adjusted as appropriate depending on the type of external skin preparation, but a suitable total blending rate is about 0.0001 to 10% by mass, and a particularly suitable blending rate is about 0.001 to 1% by mass.

[0055] An oral composition refers to a composition that is unlikely to be harmful to human health and is taken orally or by administration through the digestive tract in normal social life, and is not limited to administrative classifications such as food, medicine, and quasi-drug. Therefore, the "oral composition" in this embodiment broadly includes general foods, feed, health foods, health functional foods (special health foods, nutrient functional foods, functional food), quasi-drugs, medicines, etc. that are taken orally. The oral composition according to this embodiment contains, in the oral composition or its packaging, ononis extract, solanum root extract, golden silk extract, enmeisou extract, sanguisorba officinalis extract, shell ginger extract, etc. Things It is preferably an oral composition capable of displaying the favorable effects of the composition or a mixture thereof, and is particularly preferably a health functional food (specified health food, nutritional functional food, functional food), quasi-drug or pharmaceutical.

[0056] Oral compositions containing Ononis extract, Sophora root extract, Golden silk extract, Enmeisou extract, Sanguinea oleracea extract, and Shell Ginger extract Things The amount of these mixtures may be appropriately changed in consideration of the purpose of use, symptoms, sex, etc., but it is preferable to adjust the total amount of extracts to be taken by an adult per day to about 1 to 1000 mg, taking into consideration the general intake of the oral composition to which the addition is to be made. When the oral composition to which the addition is to be made is in the form of granules, tablets, or capsules, the amount of extracts to be taken by the oral composition to which the addition is to be made may be adjusted to about 1 to 1000 mg in total. Things The total amount of these mixtures to be added is usually 0.1 to 100% by mass, and preferably 1 to 100% by mass, based on the oral composition to which they are added.

[0057] Furthermore, the anti-glycation agent of this embodiment has an excellent anti-glycation effect and can therefore be suitably used as a reagent for research related to glycation reactions, for example, research related to the formation mechanism of AGEs or the decomposition mechanism of AGEs.

[0058] The anti-glycation agent of this embodiment is preferably applied to humans, but can also be applied to animals other than humans (e.g., mice, rats, hamsters, dogs, cats, cows, pigs, monkeys, etc.) as long as the respective action effects are exerted. EXAMPLES

[0059] The present invention will be specifically described below with reference to the following production examples and test examples, but the present invention is not limited to the following examples. In the test examples, golden silk extract (manufactured by Maruzen Pharmaceutical Co., Ltd.) was used as sample 3.

[0060] [Production Example 1] Production of Ononis extract 1500ml of 50% butylene glycol was added to 100g of dried root of Ononis, and extraction was performed by heating at 80-90℃ for 2 hours in a reflux extractor, followed by hot filtration. The obtained extract was dried to obtain Ononis extract (10g, sample 1).

[0061] [Production Example 2] Production of Sophora root extract 1500 ml of 90% ethanol was added to 100 g of dried Sophora root, and extraction was performed at 80-90°C for 2 hours in a reflux extractor, followed by hot filtration. The resulting extract was dried to obtain Sophora root extract (12 g, sample 2).

[0062] [Production Example 3] Production of Enmeisou extract 1500 ml of 50% ethanol was added to 100 g of dried Enmeisou, and extraction was performed by heating at 80-90°C for 2 hours in a reflux extractor, followed by hot filtration. The resulting extract was dried to obtain Enmeisou extract (15 g, sample 4).

[0063] [Production Example 4] Production of Sanguisorba officinalis extract 1500 ml of 50% ethanol was added to 100 g of dried Sanguisorba officinalis root, and the mixture was heated and extracted at 80-90°C for 2 hours in a reflux extractor, followed by hot filtration. The resulting extract was dried to obtain Sanguisorba officinalis extract (24 g, sample 5).

[0064] [Production Example 5] Production of shell ginger extract 1500 ml of 80% ethanol was added to 100 g of dried shell ginger leaves, and extraction was carried out at 80-90°C for 2 hours in a reflux extractor, followed by hot filtration. The resulting extract was dried to obtain shell ginger extract (3 g, sample 6). 。

[0065] [Test Example 1] AGE formation inhibitory effect test The inhibitory effect on the formation of advanced glycation end products (AGEs) of Ononis extract (sample 1), Sophora root extract (sample 2), Golden silk extract (sample 3), Enmeiso extract (sample 4) and Sanguisorba officinalis extract (sample 5) was tested as follows.

[0066] A mixture of 0.2 M D(-)-ribose and test samples (samples 1 to 5, see Table 1 for sample concentrations) prepared in PBS buffer, 100 μL of PBS buffer alone as a negative control, or 0.2 M D(-)-ribose solution prepared in PBS buffer as a positive control was added to each well of a 96-well type I collagen-coated plate (Asahi Glass Co., Ltd.), and the plate was left to stand at 37°C for two weeks to allow AGEs to form. After two weeks, the amount of AGEs was measured by ELISA using an anti-AGEs antibody (Transgenic Co., Ltd.) to evaluate the inhibitory effect on AGE formation. The AGE formation inhibition rate (%) was calculated from the results using the following formula.

[0067] AGEs formation inhibition rate (%)={(BC) / (BA)}×100 In the formula, A represents the "absorbance at a wavelength of 405 nm of the negative control," B represents the "absorbance at a wavelength of 405 nm of the positive control," and C represents the "absorbance at a wavelength of 405 nm when the test sample is added." The results are shown in Table 1.

[0068] [Table 1]

[0069] As shown in Table 1, all of Samples 1 to 5 inhibited the formation of AGEs. Therefore, it was recognized that Ononis extract (Sample 1), Sophora root extract (Sample 2), Golden silk extract (Sample 3), Enmeiso extract (Sample 4) and Sanguisorba officinalis extract (Sample 5) have excellent AGE formation inhibitory effects.

[0070] [Test Example 2] AGEs decomposition promotion test Shell ginger extract (sample 6 ) The effect of promoting the decomposition of advanced glycation end products (AGEs) was examined as follows.

[0071] 100μL of 0.2M D(-)-ribose solution prepared in PBS buffer or PBS buffer alone as a negative control was added to a 96-well type I collagen coated plate (Asahi Glass Co., Ltd.) and allowed to stand at 37℃ for 2 weeks to form AGEs. After 2 weeks, 100μL each of a solution of a test sample prepared in PBS buffer (samples 6 and 7, see Table 2 for final concentration), PBS buffer alone as a positive control, or PBS buffer alone again as a negative control was added and allowed to stand at 37℃ for another 2 weeks. After the reaction was completed, the amount of AGEs was measured by ELISA using an anti-AGEs antibody (Transgenic Co., Ltd.) to evaluate the AGEs decomposition promotion effect. From the obtained results, the AGEs decomposition promotion rate (%) was calculated using the following formula.

[0072] AGEs degradation promotion rate (%)={(BC) / (BA)}×100 In the formula, A represents the "absorbance at a wavelength of 405 nm of the negative control," B represents the "absorbance at a wavelength of 405 nm of the positive control," and C represents the "absorbance at a wavelength of 405 nm when the test sample is added." The results are shown in Table 2.

[0073] [Table 2]

[0074] Samples as shown in Table 2 6All of them promoted the decomposition of AGEs. )teeth It was found to have an excellent effect of promoting the decomposition of AGEs.

[0075] [Formulation example 1] A cream having the following composition was prepared by a conventional method. Ononis extract (sample 1) 0.2g Sophora root extract (sample 2) 0.2g Scutellaria root extract 0.1g Liquid paraffin 5.0g White beeswax 4.0g Squalane 10.0g Cetanol 3.0g Lanolin 2.0g Stearic acid 1.0g Polyoxyethylene sorbitan oleate (20E.O.) 1.5g Glyceryl monostearate 3.0g Oil-soluble licorice extract 0.1g 1,3-butylene glycol 6.0g Methyl paraoxybenzoate 1.5g Fragrance 0.1g Purified water Remainder (total amount is 100g)

[0076] [Formulation example 2] According to the composition below, a milky lotion was prepared by a conventional method. Golden Silk Extract (Sample 3) 0.10g Enmeisou extract (sample 4) 0.10g Sanguisorba officinalis extract (sample 5) 0.10g Jojoba oil 4.00g 1,3-butylene glycol 3.00g Arbutin 3.00g Polyoxyethylene cetyl ether (20E.O.) 2.50g 2.00g olive oil Squalane 2.00g Cetanol 2.00g Glyceryl monostearate 2.00g Polyoxyethylene sorbitan oleate (20E.O.) 2.00g Methyl paraoxybenzoate 0.15g Stearyl glycyrrhetinate 0.10g Phellodendron Bark Extract 0.10g Dipotassium glycyrrhizinate 0.10g Ginkgo leaf extract 0.10g Conchiolin 0.10g Phellodendron bark extract 0.10g Chamomile extract 0.10g Fragrance 0.05g Purified water Remainder (total amount is 100g) )

[0077] [Formulation example 3 〕 Tablets having the following composition were prepared by a conventional method. Ononis extract (sample 1) 1.0mg Sophora root extract (sample 2) 1.0mg Golden silk extract (sample 3) 1.0mg Enmeisou extract (sample 4) 1.0mg Sanguisorba officinalis extract (sample 5) 1.0mg Dolomite (containing 20% ​​calcium and 10% magnesium) 83.4mg Casein phosphopeptide 16.7mg Vitamin C 33.4mg Maltitol 136.8mg Collagen 12.7mg Sucrose fatty acid ester 12.0m g [Industrial Applicability]

[0078] The anti-glycation agent of the present invention can greatly contribute to the prevention or treatment of diabetic complications such as diabetic neuropathy, diabetic retinopathy, and diabetic nephropathy, the prevention or treatment of arteriosclerosis caused by protein glycation, the prevention or improvement of reduced elasticity and dullness of the skin caused by protein glycation, and the prevention or treatment of diseases such as osteoporosis and osteoarthritis caused by protein glycation.

Claims

[Claim 1] An agent for promoting the decomposition of advanced glycation end products (AGEs), characterized by having shell ginger extract as an active ingredient.

Citation Information

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