Denatured protein reducing agent and method for producing the same

Abstract

To provide: a modified protein-reducing agent that is safe and can be taken at a daily dosage or used as a functional food, and that makes it possible to reduce the amount of modified protein in a body; and a method for producing the modified protein-reducing agent.SOLUTION: A modified protein-reducing agent according to the present invention contains an above-ground portion of sesame (Sesamum indicum) or an extract thereof as an active ingredient. A method for producing a modified protein-reducing agent according to the present invention includes the steps of sowing and growing seeds of sesame (Sesamum indicum) and collecting the above-ground portion of the grown sesame.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a denatured protein reducer that is safe, can be taken daily, and can be used as a health food, and is capable of reducing denatured proteins in the body, and a method for producing the same. [Background technology]

[0002] Aging, overeating, and poor diet can lead to excess blood glucose, resulting in the glycation of intracellular and extracellular proteins, which are the building blocks of various body tissues, resulting in the production and accumulation of denatured proteins. Furthermore, animal fat foods, particularly those cooked by deep-frying, baking, or sautéing, contain advanced glycation end products (AGEs). Some artificial sweeteners, commonly used in soft drinks and confectionery, are known to produce advanced glycation end products more rapidly than glucose. These denatured proteins are highly toxic and are believed to accelerate aging. For example, they not only cause skin dullness, wrinkles, and senile spots, but also reduce flexibility and cause the decline and deterioration of various tissue functions. Furthermore, accumulation of advanced glycation end products in blood vessels can lead to myocardial infarction and cerebral infarction, while accumulation in bones can lead to osteoporosis. Accumulation of advanced glycation end products in the eyes can contribute to cataracts, thereby affecting overall health (Patent Documents 1-8, Non-Patent Documents 1-7). Hemoglobin A1c, which is used to diagnose diabetes, is also a type of advanced glycation end product.

[0003] Although there have been many reports on the relationship between human diseases and advanced glycation end products, on the inhibition of the formation of advanced glycation end products, and on natural products that decompose advanced glycation end products, there are no safe and inexpensive pharmaceuticals or natural products that have shown specific ameliorative effects when ingested by humans. Because denatured proteins are thought to accumulate in the body in extremely small amounts due to lifestyle habits, etc., safe pharmaceuticals that can be taken daily would be even more desirable.

[0004] Sesame has long been known as a highly nutritious food and is also used as a herbal medicine. In addition, due to its high oil content, sesame oil is also extracted. Sesamin contained in sesame is said to exhibit various physiological activities such as antioxidant action, cholesterol absorption inhibition, and anticancer action.

[0005] Regarding sesame, mainly the seeds are used for food and research, and little is known about the physiological activities of the above-ground parts other than the seeds such as the leaves. In the "Shennong Bencaojing", the oldest pharmacology book in China, the efficacy and effects of sesame seeds and leaves are described, and similar descriptions can also be found in the "Shiwubencao" published in the Yuan Dynasty, but the nutritional physiology and medical evaluation when consumed by humans are unclear. Even today in West Africa, the thinning vegetables of sesame are used as food, and the young leaves are also used as ingredients such as putting them in soup and eating them.

[0006] For example, there is a report on the radical scavenging activity of sprouts 4 days after germinating sesame seeds (Non-Patent Document 8). However, no reports are found on the physiological activities of the above-ground parts more than 5 days after germination.

Prior Art Documents

Patent Documents

[0007]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Patent Document 5

Patent Document 6

Patent Document 7

Patent Document 8

Non-Patent Literature

[0008]

Non-Patent Literature 1

Non-Patent Literature 2

Non-Patent Literature 3

Non-Patent Literature 4

Non-Patent Literature 5

Non-Patent Literature 6

Non-Patent Literature 7

Non-Patent Literature 8

Summary of the Invention

Problems to be Solved by the Invention

[0009] As described above, denatured proteins such as advanced glycation end products cause various disorders and diseases in the body, and various components having a reducing effect thereon have been studied. However, there is no known component that is safe enough to be taken constantly and can actually reduce denatured proteins in the body when administered to humans. Therefore, an object of the present invention is to provide a denatured protein reducing agent that is safe, can be taken daily, can be used as a health food, and can reduce denatured proteins in the body, and a method for producing the same.

Means for Solving the Problems

[0010] The present inventors have conducted intensive research to solve the above problems. As a result, they have found that the above-ground part of sesame, which is edible and safe, contains components that can effectively reduce denatured proteins in the body, and thus completed the present invention. The present invention is shown below.

[0011] [1] A denatured protein reducing agent characterized by containing the above-ground part of sesame (Sesamum indicum) or an extract thereof as an active ingredient. [2] The denatured protein reducing agent according to [1], wherein the denatured protein is an advanced glycation end product. [3] The denatured protein reducing agent according to [1], wherein the denatured protein is a protein multimer. [4] A method for producing a denatured protein reducing agent, comprising: a step of sowing and growing sesame (Sesamum indicum) seeds, and a step of collecting the above-ground part of the grown sesame, characterized by including these steps. [5] The method according to [4], wherein the above-ground part of sesame with one or more buds and before flowering is collected. [6] The method according to [4] or [5], further comprising a step of extracting the active ingredient from the above-ground part of sesame using a solvent. [7] The method according to [6], wherein an alcohol-based solvent is used as the solvent.

Effects of the Invention

[0012] Since the active ingredient of the denatured protein reducing agent according to the present invention is contained in the above-ground part of sesame, which is also used for food, it is safe and can be ingested constantly every day. Further, the denatured protein reducing agent according to the present invention can actually reduce denatured proteins by administering to subjects in whom the accumulation of denatured proteins is a problem. Therefore, the present invention is extremely excellent industrially as a product that contributes to people's constant health as a health food or the like.

Brief Description of Drawings

[0013]

Figure 1

Figure 2

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Figure 6

Modes for Carrying Out the Invention

[0014] The denatured protein-reducing agent of the present invention contains the aerial parts of sesame (Sesamum indicum) or an extract thereof as an active ingredient. In the present disclosure, the term "active ingredient" refers to a component contained in the denatured protein-reducing agent of the present invention that has the effect of reducing denatured protein. In other words, the denatured protein-reducing agent of the present invention contains the aerial parts of sesame or an extract thereof in an amount sufficient to exert the effect of reducing denatured protein. Specifically, the proportion of the aerial parts of sesame or an extract thereof in the denatured protein-reducing agent of the present invention can be, for example, 10% by mass or more and 100% by mass or less.

[0015] Sesame (Sesamum indicum) is an annual plant of the Pedaliaceae family, and is said to have approximately 3,000 species, based on differences in seed shape, size, color, etc. The type of sesame is not particularly limited, but the inventors have experimentally confirmed that Sa Mong Nan Net Thae and Sesame Zou have an excellent effect of reducing denatured proteins.

[0016] Sa Mong Nan Net Thae, a small-grain black sesame seed that has been cultivated in a specific region of Myanmar for a long time, is also known as "Goma Kurohachi (registered trademark)." While Sa Mong Nan Net Thae seeds are very similar in weight and appearance to the seeds of registered lignan sesame (Registration No. 19697, Application No. 20790, Agricultural Plant Species: Sesamum indicum L., Variety Name: ITCFA2001; Registration No. 19698, Application No. 20791, Agricultural Plant Species: Sesamum indicum L., Variety Name: ITCFA2002), the present inventors have demonstrated through genome analysis that these two varieties are evolutionarily distinct, with large insertions and deletions observed between their genomes. Genomic differences between Goma Kurohachi and lignan sesame can be verified by PCR.

[0017] Gomazou is a high-lignan variety that can be cultivated in Japan, selected from the crossbred offspring of the high-yield white sesame line Toyama016 and the tropical genetic resource line H65 native to southern China with high sesamin and sesamolin contents.

[0018] The above-ground part refers to the part that is not underground and can be seen from the ground when sesame seeds are sown and grown. The above-ground part of sesame can be obtained by cutting and removing the underground part from the grown sesame.

[0019] The above-ground part of sesame is preferably, for example, from a plant with two or more true leaves. Also, the above-ground part of sesame is preferably harvested before fully mature seeds are formed. Moreover, those with a plant height of 50 cm or more, those with one or more buds before flowering, those until one or more flowers are seen, etc. can also be harvested. The period from sowing to harvesting can be adjusted as appropriate, but for example, it can be one month or more, preferably two months or more or 2.5 months or more, and can be 3.5 months or less, preferably 3 months or less.

[0020] The above-ground part of sesame may be used as it is, but for example, one or more treatments selected from washing with water, drying, pulverization, hydrolysis, and extraction may be performed. As the hydrolysis treatment, for example, it can be treated at 25 ± 5°C and a humidity of 90% or more for 1 hour or more and 5 hours or less, or rotated in a drum and then heated to stop hydrolysis. Hydrolysis treatment may reduce bitterness.

[0021] The form of the active ingredient of the denatured protein reducing agent according to the present invention is not particularly limited, and examples include liquid, paste, and powder. Powders include coarse powder, micropowder, and nanomicropowder.

[0022] The form of the denatured protein reducing agent according to the present invention is not particularly limited, and examples include solid, gel, and liquid. More specifically, powders, fine granules, granules, tablets, coated tablets, capsules, lozenges, and liquids, etc. are included. The denatured protein reducing agent according to the present invention may contain additives other than the active ingredient depending on its dosage form. Examples of the additives include excipients, binders, lubricants, disintegrants, emulsifiers, stabilizers, absorption promoters, differentiating agents, and preservatives, and the blending amount thereof is not particularly limited and may be appropriately adjusted.

[0023] The denatured protein reducing agent according to the present invention can be produced, for example, by a method including the following steps.

[0024] 1. Flax sowing and growing step In this step, flax seeds are sown and grown. This step may be carried out according to the normal method of growing flax. For example, flax seeds may be sown from mid-May to mid-June in Japan after the maximum temperature exceeds 20°C. Specifically, holes about 1 cm deep are made, 5 to 6 seeds are placed in each hole, and then covered with soil and sufficiently watered. When there are 1 to 2 true leaves, thin out the poorly growing ones so that there are about 3 plants in one place, and thin out to 2 plants when there are 3 to 4 true leaves and to 1 plant when there are 5 to 6 true leaves.

[0025] 2. Flax above-ground part collection step In this step, the above-ground part of the grown flax is collected. Specifically, the above-ground part may be separated from the underground part of the grown flax. The collection time and post-treatment are as described above.

[0026] 3. Extraction step In this step, the active ingredient is extracted from the above-ground part of flax using a solvent. This step may or may not be carried out, but extraction may further enhance the denatured protein reducing effect of the active ingredient.

[0027] The solvent used for extraction in this process is not particularly limited and can be appropriately selected. From the perspective of safety, for example, aqueous solvents can be mentioned. Aqueous solvents refer to water, a mixed solvent of water and a water-soluble organic solvent, or a water-soluble organic solvent. The proportion of the water-soluble organic solvent in the mixed solvent can be adjusted as appropriate. For example, it can be 50% by mass or more, preferably 60% by mass or more or 65% by mass or more, and more preferably 70% by mass or more. Examples of water-soluble organic solvents include alcohol solvents such as methanol and ethanol; ether solvents such as tetrahydrofuran; amide solvents such as dimethylformamide and dimethylacetamide; and sulfoxide solvents such as dimethyl sulfoxide. From the perspective of relatively less harm to the human body, ethanol is a preferred water-soluble organic solvent. Also, the type of water is not particularly limited, and purified water, distilled water, pure water, tap water, etc. can be used without particular limitation.

[0028] The extraction conditions in this process are not particularly limited, and conventional methods can be used. For example, about 5 mL or more and 100 mL or less of the solvent can be added per 1 g of the above-ground part of sesame, and extraction can be carried out for about 30 minutes or more and 10 hours or less. The extraction temperature is also not particularly limited. Extraction can be carried out at room temperature, at a temperature below the boiling point of the solvent, or by heating under reflux. For example, when water is used as the solvent, it can be heated at 60°C or more and 100°C or less.

[0029] After extraction, general post-treatment can be carried out. For example, solid components can be removed from the extracted mixture by filtration or centrifugation. Further, the obtained solution can be distilled, concentrated, or dried. Examples of drying methods include heat drying, vacuum drying, freeze drying, and spray drying. Also, the active ingredient can be further purified by chromatography or the like.

[0030] The dosage of the denatured protein reducing agent according to the present invention should be appropriately adjusted according to whether it is for preventive use or therapeutic use, the severity of the patient, other conditions, age, gender, etc., and is not particularly limited. For example, when the denatured protein reducing agent according to the present invention is taken orally, it can be used at 10 mg or more per day in terms of solid content, and when used externally, it can be used at 100 mg or more. Since the denatured protein reducing agent according to the present invention is very safe, the upper limit of the dosage is not particularly limited. For example, when taken orally, it can be 2 g or less per day in terms of solid content, and when used externally, it can be 5 g or less. Also, the number of times of use per day can be about 1 time or more and 5 times or less.

[0031] The denatured protein reducing agent according to the present invention can be administered not only to humans but also to animals other than humans. Examples of animals other than humans to be administered include livestock such as horses, cows, pigs, sheep, goats, camels, and llamas; race animals such as racehorses; pet animals such as dogs and cats; experimental animals such as mice, rats, guinea pigs, and rabbits; poultry such as chickens, ducks, turkeys, and ostriches; and fish and shellfish such as farmed fish.

[0032] The denatured protein reducing agent according to the present invention has an extremely excellent denatured protein reducing effect. Specifically, it exhibits effects such as suppressing glycation and multimerization of proteins, decomposing denatured proteins once formed, and activating the activity of proteolytic enzymes of denatured proteins. Therefore, the denatured protein reducing agent according to the present invention is effective for the prevention and treatment of diseases and symptoms involving protein denaturation. Such diseases and symptoms include, for example, skin wrinkles, spots, dark circles, sagging, etc.; diabetic complications such as cataracts, arteriosclerosis, and renal dysfunction; aging such as memory impairment and dementia; and cancer.

Examples

[0033] Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited by the following examples, and it is of course possible to appropriately modify and implement it within the range that conforms to the gist of the foregoing and following descriptions, and all of them are included in the technical scope of the present invention.

[0034] Example 1 Small black sesame seeds that have been cultivated in a specific region of Myanmar for a long time and are locally called Sa Mong Nan Net Thae (hereinafter abbreviated as "SMNNT") were sown. Approximately three months later, when flower buds appeared, the above-ground part was cut off from the underground part and removed, and then dried at 37°C for 72 hours. The obtained dried SMNNT above-ground part was pulverized with a hammer mill.

[0035] Example 2 2 g of the dried SMNNT above-ground part powder from Example 1 was mixed with 40 mL of water and heated at 80°C for 1 hour. Subsequently, it was filtered and centrifuged to obtain an extract after removing the solid content. 5 mL was taken from the obtained extract, heated at 105°C for 1 hour to remove the solvent, and the solid content was measured.

[0036] Example 3 An extract was obtained and the solid content was measured in the same manner as in Example 2, except that 70% ethanol water was used instead of water and it was heated at 50°C for 4 hours.

[0037] Example 4 Above-ground part powder of Gomazou, a variety of sesame, was obtained in the same manner as in Example 1, except that Gomazou, a variety of sesame, was used instead of SMNNT.

[0038] Example 5 An extract was obtained and the solid content was measured in the same manner as in Example 2, except that the above-ground part powder of Gomazou from Example 4 was used.

[0039] Example 6 An extract was obtained and the solid content was measured in the same manner as in Example 3, except that the above-ground part powder of Gomazou from Example 4 was used.

[0040] Example 7: Genome analysis The seeds of SMNNT closely resemble the seeds of so-called lignan sesame in terms of the number of seeds per gram and color tone. Therefore, DNA was prepared from both and genome analysis was performed. The base number of the sesame genome is known to be approximately 270 million bases. In our genome analysis, we obtained sequence data about 55 times the base number of the sesame genome per variety, which means that any genomic region was analyzed 55 times. Therefore, probabilistically speaking, all genomic regions are covered, and it is judged that reading errors can be corrected by the analysis program. As a result of genome analysis, it became clear that SMNNT and lignan sesame are evolutionarily different varieties, such as large insertions and deletions in the sequences between the genomes of SMNNT and lignan sesame. From the obtained analysis data, the differences in the genomes of SMNNT and lignan sesame can be verified by PCR.

[0041] Test Example 1: Evaluation of the inhibitory effect on the formation of AGEs-modified protein crosslinks The inhibitory effect on the formation of AGEs-modified protein crosslinks was evaluated with reference to the method described by Perera H.K.I. et al., Asian J. Med. Sci., 6(1), 28 - 33 (2015). Specifically, 0.1 mol / L phosphate buffer (pH 7.4), each extract, lysozyme as the protein, and fructose as the sugar were mixed and incubated at 60 °C for 40 hours. The concentrations of lysozyme and fructose were adjusted to 5 mg / mL and 0.5 mol / L, respectively. The added amount of each extract was adjusted from each solid content so that the solid content concentration would be as shown in FIGS. 1 and 2. Also, as a control, an extraction solvent was added instead of the extract, and as a positive control, aminoguanine was added. For comparison, a reaction solution was obtained in the same manner without adding fructose. The obtained lysozyme saccharification reaction solution, distilled water, and 2-mercaptoethanol sample solution were mixed and reacted at a ratio of 5:5:2 (volume ratio). Subsequently, the cross-linking reaction was stopped by heating at 95 °C for 5 minutes. After cooling, SDS-PAGE electrophoresis was performed according to the conventional method. The gel concentration was 4-20% and the current value was 20 mA. After electrophoresis, the lysozyme band was stained with CBB and decolorized with methanol-acetic acid. The results are shown in Figures 1 and 2. The molecular weight of the monomer of lysozyme is 13.1 kDa, the molecular weight of the dimer is 25.8 kDa, and the molecular weight of the trimer is 40.5 kDa. In Figures 1 and 2, "Fru" represents fructose and "AG" represents aminoguanine. The explanations of the lanes in Figure 1 are shown in Table 1, and the explanations of the lanes in Figure 2 are shown in Table 2.

[0042]

Table 1

[0043]

Table 2

[0044] As shown in the results of Figures 1 and 2, lysozyme was saccharified by fructose, and further dimerized particularly by 2-mercaptoethanol, and the formation of trimers was also observed. In contrast, the formation of dimers was suppressed by the SMNNT and the aerial part extract of Sesamum indicum, and trimers were hardly observed.

[0045] Next, the photographed images of each gel were processed by the image processing software "ImageJ", the intensities of the bands corresponding to the protein dimers and trimers were quantified, and the cross-linking formation inhibition rate was calculated by the following formula. The results are shown in Figure 3. Cross-linking formation inhibition rate (%) = [{(intensity of the band with extract and fructose addition) - (intensity of the band with extract addition and fructose absence)} / {(intensity of the band with solvent and fructose addition) - (intensity of the band with solvent addition and fructose absence)}] × 100 As shown in the results of Fig. 3, compared with aminoguanidine, which is a positive control, all the extracts according to the present invention effectively suppressed the cross-linking of proteins. In particular, the 70% ethanol extract showed a stronger cross-linking inhibitory effect than the hot water extract. Also, the 70% ethanol extract derived from the above-ground part of SMNNT showed a stronger cross-linking inhibitory effect than the extract from the above-ground part of Seseli mairei. Furthermore, the cross-linking inhibitory effect of the extract derived from the above-ground part of SMNNT was stronger than that of aminoguanidine, which is a positive control.

[0046] Test Example 2: Evaluation of AGEs cross-link cleavage effect The cleavage effect of the above-ground part of SMNNT on the AGEs protein cross-link that had already formed was evaluated with reference to Vasan S et al., Nature, 382, 275-278 (1996). Specifically, the above-ground part extract of SMNNT in Example 3, or N-phenacylthiazolium bromide (PTB) as a positive control, 10 mmol / L 1-phenyl-1,2-propanedione (PPD), and 0.2 mol / L phosphate buffer (pH 7.4) were mixed so that the extract solid content:PPD:phosphate buffer = 5:1:4 (mass ratio), and reacted at 37 °C for 8 hours (n = 3). When a substance having a cleavage effect on the protein cross-link is included in the reaction system, PPD is decomposed to produce benzoic acid as shown in the following reaction formula.

[0047]

Chemical formula

[0048] Next, 0.7 mol / L hydrochloric acid was added to stop the reaction. After centrifuging the reaction solution, the amount of benzoic acid in the supernatant was analyzed by HPLC, and the AGEs cross-link cleavage rate was determined by the following formula. The experiment was performed in three replicates. The results are shown in Fig. 4. AGEs cross-link cleavage rate (%) = [(amount of benzoic acid in the sample addition solution - amount of benzoic acid in the control solution) / amount of PPD used in the reaction] × 100 As shown in the results of Fig. 4, it was shown that the extract of the above-ground part of SMNNT had a stronger cleavage effect on AGEs cross-links than PPD, which is a positive control.

[0049] Test Example 3: Evaluation of oxidative protease activation Glycated and oxidized damaged proteins are degraded by oxidative protease (OPH). Therefore, we evaluated the activity of acylaminoacid releasing enzyme (Takara Bio Inc., hereafter abbreviated as AARE) and N-acetyl-L-alanine-p-nitroanilide (Bachem, hereafter abbreviated as AAPA) as a substrate to activate oxidative protease. The extract from Example 2 or Example 3 was mixed with 0.1 mol / L Tris-HCl (pH 7.4), 2 mmol / L AAPA, 1 mU / mL AARE, and the extract solids to the concentrations shown in Figure 5. 250 μL of the resulting mixture was incubated at 37°C for 60 minutes, and the amount of liberated p-nitroanilide (hereinafter abbreviated as "pNA") was measured by spectrophotometer at absorbance at 405 nm. As a control, distilled water was used instead of the extract. Based on the measured values, the OPH activation rate was calculated using the following formula. The results are shown in Figure 5. OPH activation rate (%) = [(optical density 60 minutes after the start of the reaction - optical density immediately after the start of the reaction) / (optical density 60 minutes after the start of the control reaction - optical density immediately after the start of the control reaction)] × 100 As shown in Figure 5, it was revealed that the extract of the aerial parts of SMNNT strongly enhances the activity of oxidative protease that breaks down AGEs.

[0050] Test Case 4: Clinical Trial A placebo-controlled, randomized, single-blind, parallel-group comparative study to verify the effect on the accumulation of denatured proteins in human skin was conducted in compliance with the Ministry of Education, Culture, Sports, Science and Technology, the Ministry of Health, Labor and Welfare, and the Ministry of Economy, Trade and Industry Notification No. 1, "Ethical Guidelines for Life Science and Medical Research Involving Human Subjects" (issued March 23, 2021). A total of 57 subjects were randomly selected regardless of gender, age, etc. First, the AGEs age of the skin before eating was measured using an AGE Scanner (manufactured by Diagnoptics Technologies). From the night of that day, the above-ground part powder of SMNNT of Example 1 was ingested twice a day, 1.5 g each time, in the morning and at night for 6 months. The measurement was carried out once a month, and the test was carried out without special instructions regarding other dietary contents and lifestyle habits. In the placebo group, instead of the above-ground part powder of SMNNT, moringa powder was ingested in the same way and measured. For the subjects in their 20s, the AGEs age measured by the AGE Scanner was on average 19.5 ± 6.5 years old, and the difference between the first measurement age of AGEs and the actual age was within 10 years. Also, for the subjects in their 40s, the average was 42.7 ± 4.2 years old, and the difference between the first measurement age of AGEs and the actual age was also within 10 years, and the difference from the actual age was not so obvious. However, when it came to the 50s, a large variation was seen. The average was 52.9 ± 4.0, but there were also subjects with a difference of about 20 to 30 years between the first measurement age of AGEs and the actual age. It is presumed that long-term lifestyle habits, especially diet, over 15 years or 20 years, etc., are involved in the abnormal accumulation of AGEs. Among the subjects with an AGEs age of 20 to 40 years old at the start, the accumulation of denatured proteins in the skin was small, and no significant effect was seen in the placebo group. However, in the measurement by the AGEs Scanner, for the 7 subjects aged 54 to 76 years old whose AGEs age at the start of the test was 70 years old or more, the average AGEs age at the start was 78.4 ± 3.4 years old, and after ingesting the selected UPS powder of SMNNT for only 6 months, it became 69.6 ± 5.3 years old, and a decreasing trend was confirmed. The results are shown in Figure 6.

Claims

**Claim 1**: A modified protein degrading agent characterized by containing the leaves of Sa Mong Nan Net Tha, or an extract thereof, as an active ingredient. **Claim 2** The modified protein degrading agent according to claim 1, wherein the modified protein is an advanced glycation end product. **Claim 3** The modified protein degrading agent according to claim 1, wherein the modified protein is a protein multimer. **Claim 4** A method for producing a modified protein degrading agent, comprising: a step of sowing and growing the seeds of Sa Mong Nan Net Tha, and a step of collecting the grown leaves of Sa Mong Nan Net Tha. **Claim 5** The method according to claim 4, wherein the above-ground part of sesame with one or more flower buds and before flowering is collected. **Claim 6** The method according to claim 4, further comprising a step of extracting the active ingredient from the leaves of Sa Mong Nan Net Tha using a solvent. **Claim 7** The method according to claim 6, wherein an alcohol-based solvent is used as the solvent.

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