An enzyme composition with excellent enzyme activity, using black garlic components as an enzyme carrier.
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2025-02-03
- Publication Date
- 2026-08-14
AI Technical Summary
【0011】 本発明に係る酵素組成物の作用効果は摂取後の血液中のメチル化ヌクレオソームの低減効果により判定した。メチル化ヌクレオソームはガンを含む疾病の状態を客観評価するために使用されているからである(特許文献4及び非特許文献6、7)。本発明の酵素組成物のDDS機能および活性酸素消去機能とメチル化ヌクレオソームの低減効果との因果関係の詳細は定かでないが、本発明に係る酵素組成物の具体的効果の判断の根拠の一つとなる。すなわち、本発明の効果は、熟成植物酵素液を熟成黒にんにくペーストに担持させることにより黒にんにくの抗赤血球凝集効果により植物酵素成分の毛細血管を介しての細胞へのDDS機能が高まり、しかも酵素組成物には補酵素としてアムラを配合して酵素とともに配給されるので酵素の生体反応で生成する活性酸素を消去することにより発揮されるものと思われるからである。そこで、摂取後の血液中の正電荷を有するヌクレーソーム(メチル化ヌクレオソーム)の定量により本発明の酵素組成物の効果の判定を行った。 メチル化ヌクレオソームは非特許文献6において、各臓器のがん抑制遺伝子の不活性化の指標として教示されており、本発明の黒にんにく成分に担持される酵素組成物はメチル化ヌクレオソームの低減効果に優れることは本発明の効果の主たるものである。メチル化ヌクレオソームは身体の免疫機能の増加とともに減少するといわれているが、その効果が熟成黒にんにくの各種機能、特にその抗赤血球凝集作用により、酵素及び補酵素の細胞内へのDDS機能が高まり、その相乗効果に基づくものと思われる。本発明に係る酵素組成物は熟成植物酵素液とともにハナビラタケを熟成植物酵素液に対し半量から1/4量を添加するようにしてハナビラタケのDDS機能を高めることができる。すなわち、黒にんにく成分、酵素成分及び補酵素成分との相乗効果が発揮され、ハナビラタケのベータグルカンの細胞への浸透効果が高まるものと思われる。
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Abstract
Description
[Technical Field]
[0001] The present invention relates to an enzyme composition with excellent enzyme activity, using black garlic components as a carrier, and more specifically, to an enzyme composition having the effect of reducing methylated nucleosomes (positively charged nucleosomes) as an enzyme activity. [Background technology]
[0002] Various enzymes are understood to act as catalysts that promote biological reactions, and many matured plant enzyme extracts are used as supplements to enhance the immune function of the body. Considering these biological enzymatic reactions, the enzymatic reaction shown in Figure 1 is presented. Specifically, it has been reported that the reaction occurs when an apoenzyme formed by protein synthesis in the body combines with a prosthetic group to form a holoenzyme, which then binds to a substrate to produce a product, while the enzyme returns to a holoenzyme by the coenzyme, and this process is repeated. Therefore, in order to activate this enzymatic reaction, it is necessary to first improve the DDS function that appropriately delivers enzymes into cells to promote the enzymatic reaction, and secondly, to eliminate the effects of reactive oxygen species produced by the enzymatic reaction.
[0003] Red blood cells are responsible for delivering enzymes to cells in the body. Red blood cells are divided into a cell membrane on the surface and cytoplasm inside. It is well known that oxygen and carbon dioxide are exchanged through the cell membrane, and then transported by hemoglobin in the cytoplasm and the action of enzymes. However, when red blood cells aggregate, the delivery of red blood cells from capillaries into cells becomes impossible or insufficient, resulting in poor blood circulation. This is because red blood cells bend and deform to pass through capillaries, but aggregation makes passage difficult. Therefore, when ingesting enzymes, it is necessary to have excellent DDS (Drug Delivery System) functions that suppress red blood cell aggregation and deliver red blood cells to cells along with the enzymes via capillaries.
[0004] On the other hand, enzymes alone are inactive; they require certain low-molecular-weight organic compounds to exhibit enzymatic activity. These low-molecular-weight organic compounds essential for enzymatic activity are called coenzymes. While many of these coenzymes are produced in the body from vitamins, B vitamins and niacin are particularly well-known coenzymes, and many people currently supplement them as supplements. [Prior art documents] [Patent Documents]
[0005] [Patent Document 1] 1738379173442_01738379173442_1 "Manufacturing and Uses of Black Garlic Extract" [Patent Document 2] 1738379173442_21738379173442_3 "Method for producing black garlic" [Patent Document 3] Japanese Patent Publication No. 2021-108652, "Novel Black Garlic Extract Using Garlic Cloves as the Main Ingredient and Method for Producing the Same" [Patent Document 4] WO2021 / 1323576 "Liquid biopsy method using autofluorescence targeting nucleosomes fragmented by apoptosis" [Non-patent literature]
[0006] [Non-Patent Document 1] Idris AR, Afegbua SL., Trans. R.Soc.Trop.Med.Hyg., 111, 478 (2017). [Non-Patent Document 2] Baluchnejadmojarad T, Kiasalari Z, Afshin-Majd S, Ghasemi Z, Roghani M., Eur.J.Pharmacol., 5, 69-76 (2017) [Non-Patent Document 3] Block E, Bechand B, Gundala S, Vattekkatte A, Wang K, Mousa SS, Godugu K, Yalcin M, Mousa SA., Molecules., 22(12). pii: E2081. doi: 10.3390 / molecules22122081. [Non-Patent Document 4] Oboh G, Ademiluyi AO, Agunloye OM, Ademosun AO, Ogunsakin BG., J Diet Suppl. 16, 105-118(2019). [Non-Patent Document 5] Zhang H, Wang P, Xue Y, Liu L, Li Z, Liu Y., Tissue Cell. 50, 89-95(2018). [Non-Patent Document 6] "Epigenetics and Carcinogenesis," Yoshimasa Nobuyama and Toshikazu Ushijima, Clinical Chemistry 36:288-295, 2007. [Non-Patent Document 7] "Silver Nanoscale Hexagonal Column Chips for Detecting Cell-free DNA and Circulating Nucleosomes in Cancer Patients" Hiroaki Ito etc. SCIENTIFIC REPORTS Published:23 May 2015 [Overview of the Initiative] [Problems that the invention aims to solve]
[0007] Therefore, it is necessary to improve the appropriate and sufficient delivery of plant enzymes to cells (DDS function) and to promote sufficient biological reactions of plant enzymes within cells with the assistance of appropriate coenzymes. The objective is to provide an enzyme composition that excels in both of these functions. [Means for solving the problem]
[0008] However, it is difficult to determine the pharmacological effects of the DDS function and enzyme activity scavenging function of enzyme compositions. Therefore, the inventors considered that in many diseases, due to the symptoms, nucleosomes consisting of fragmented DNA and histones are released into the bloodstream through apoptosis, and that these nucleosomes are methylated depending on the severity of the disease, increasing the number of positively charged nucleosomes (Non-Patent Documents 6 and 7). With this in mind, the inventors diligently conducted research while determining the effects using a method (Patent Document 4) that can selectively capture methylated nucleosomes (positively charged nucleosomes) and measure their autofluorescence. As a result, firstly, it was thought that anti-erythraglutination activity is effective in improving the DDS function of enzyme compositions, and it was confirmed that black garlic possesses this function (Figure 1), and furthermore, it was confirmed that black garlic contains various coenzymes that assist the biological reactions of enzymes. Furthermore, we found that using black garlic as an enzyme carrier not only promotes the DDS function of enzyme components but also reduces the aforementioned methylated nucleosomes, possibly due to its role as a coenzyme donor (Figure 3). Secondly, it is known that enzyme reactions produce reactive oxygen species that inhibit biological reactions, and that a coenzyme with high SOD activity is necessary to eliminate these. Therefore, among coenzymes with excellent SOD activity, we found that amla (Amla molasses) not only has a high SOD value (380,000: measured by the Japan Food Research Laboratories) equivalent to or higher than ascorbic acid, but also contains other coenzyme components, making it an inexpensive and effective component for constructing enzyme compositions. Therefore, based on this knowledge, and as a result of diligent research, the present invention firstly uses black garlic as an enzyme carrier in the aged enzyme solution to enhance the DDS function of the enzyme component, thereby increasing the anti-aggregation effect of the enzyme transporter on red blood cells and providing coenzyme components to the enzyme component. Secondly, it selects amla (Yu Gan Zi), which has excellent SOD function, as a component to remove the effects of reactive oxygen species produced by the enzymatic reaction, and by supplying coenzyme components, it has completed an enzyme composition that has excellent in vivo enzyme activity and can reduce methylated nucleosomes (positively charged nucleosomes). In other words, the present invention is an enzyme composition comprising, by weight, an equal to five times the amount of black garlic paste relative to the aged plant enzyme solution, half to one-fifth the amount of amla (Yu Gan Zi) powder relative to the aged plant enzyme solution, and an appropriate amount of oligosaccharide. Even if the amount of black garlic paste is equal to or greater than the amount of the aged plant enzyme solution, no improvement in the anti-erythrocyte agglutination effect can be expected, and if it is less than one-fifth the amount, the anti-erythrocyte agglutination effect is insufficient; therefore, the amount was set to between equal and one-fifth. For the coenzyme amla (Yu Gan Zi), even if it is more than half the amount of the aged plant enzyme solution, no improvement in reactive oxygen species scavenging can be expected, and if it is less than one-quarter the amount, it is insufficient; therefore, the amount was set to between half and one-quarter. On the other hand, since the enzyme composition of the present invention has enhanced DDS (drug delivery system) function, considering the usual single-dose amount, half to one-quarter the amount of Sparassis crispa powder was added to the aged plant enzyme solution to complete the second enzyme composition.
[0009] In this invention, "aged plant enzyme liquid" refers to a commercially available plant enzyme liquid (specific gravity 1.10 to 1.20) containing plant enzyme extracts obtained by fermenting various plants and fruits, including wild grasses, through long-term aging. In this invention, commercially available Marumi Enzyme (specific gravity 1.12) was used for the experiments. Furthermore, "aged black garlic paste" refers to black or brown garlic produced by fermenting raw garlic using a standard method. Various commercially available products can be used, but in this case, a homemade product was used. In addition, "amla" refers to the dried powder of the fruit of a deciduous tree belonging to the genus Phyllanthus in the family Phyllanthaceae, and is usually sold commercially as a high-value medicine with an SOD value of 100,000 or more. In this case, commercially available amla powder (manufactured by Shanghai Yuan Lu Jing Mao Co., Ltd.) with an SOD value of approximately 300,000 was used.
[0010] Incidentally, garlic (Allium sativum) has been popular since ancient times not only as a food used for nourishing and strengthening the body, but also for its antibacterial properties (Non-Patent Literature 1). ) , anti-inflammatory effect (non-patent document 2) ) , antitumor effect (Non-patent document 3) ) , antidiabetic effect (non-patent document 4) ) , antioxidant activity (Non-patent document 5) )It has been reported that garlic possesses many physiological activities, and black garlic is produced by fermentation, which involves gradually maturing garlic in an environment of 60-90% humidity and 40-90°C, or by Maillard reaction (aminocarboxyl reaction) treatment, and improvements to the production method have also been made (Patent Documents 1 and 2). In this black garlic, it has been reported that many functional components increase during the maturation process, and in particular, an increase of about eight times has been observed in GABA (γ-aminobutyric acid). However, since GABA is extremely easily broken down in the body, in order to provide compositions and foods that can improve the effective utilization rate of GABA in the body, a composition for inhibiting GABA (γ-aminobutyric acid) degrading enzymes has also been proposed (Patent Document 3), but it has never been used in combination with plant enzyme liquid or amla. Therefore, the inventors focused on the fact that black garlic, which has various functions separate from its GABA-degrading enzyme inhibitory effect, not only contains coenzyme components but also has an excellent anti-erythrocyte agglutination effect. Using this as an enzyme carrier, they created an enzyme composition that enhances the enzyme's DDS function and improves enzyme activity. [Effects of the Invention]
[0011] The action and effect of the enzyme composition according to the present invention were determined by the effect of reducing methylated nucleosomes in the blood after ingestion. This is because methylated nucleosomes are used to objectively evaluate the state of diseases including cancer (Patent Document 4 and Non-Patent Documents 6 and 7). Although the detailed causal relationship between the DDS function and the active oxygen scavenging function of the enzyme composition of the present invention and the effect of reducing methylated nucleosomes is not clear, it is one of the bases for judging the specific effects of the enzyme composition according to the present invention. That is, the effect of the present invention is that by supporting the aged plant enzyme solution on the aged black garlic paste, the DDS function of the plant enzyme component to cells via capillaries is enhanced by the anti-erythrocyte aggregation effect of black garlic, and moreover, amla is blended as a coenzyme in the enzyme composition and distributed together with the enzyme, so it is considered to be exerted by scavenging active oxygen generated in the biological reaction of the enzyme. Therefore, the effect of the enzyme composition of the present invention was determined by quantifying nucleosomes (methylated nucleosomes) having a positive charge in the blood after ingestion. In Non-Patent Document 6, methylated nucleosomes are taught as an indicator of the inactivation of tumor suppressor genes in each organ. The main effect of the present invention is that the enzyme composition supported by the black garlic component of the present invention has an excellent effect of reducing methylated nucleosomes. Although it is said that methylated nucleosomes decrease as the body's immune function increases, its effect is considered to be based on the synergistic effect that the DDS function of the enzyme and coenzyme into cells is enhanced by various functions of aged black garlic, particularly its anti-erythrocyte aggregation effect. The enzyme composition according to the present invention can enhance the DDS function of Flammulina velutipes by adding Flammulina velutipes to the aged plant enzyme solution in an amount of half to one-fourth of the aged plant enzyme solution. That is, the synergistic effect of the black garlic component, the enzyme component and the coenzyme component is exerted, and it is considered that the penetration effect of beta-glucan of Flammulina velutipes into cells is enhanced.
Brief Description of the Drawings
[0012] [Figure 1] It is a schematic diagram showing the in-vivo reaction of an enzyme. [Figure 2]It is an explanatory diagram showing the state of transition from the aggregated state (a) to the dispersed state (b) of red blood cells. [Figure 3] It is a graph showing the tendency of the amount of methylated nucleosomes to decrease by the ingestion of the enzyme of the present invention. [Figure 4A] A method for measuring nucleosomes having a positive charge in blood is shown in process diagrams (a), (b), and (c). [Figure 4B] It shows the analysis range of the chip. [Figure 4C] It shows the quantification of the area of the chip. <
Mode for Carrying Out the Invention
[0013] Hereinafter, based on specific examples of the present invention, it will be described in detail. The inventors investigated the above problem. As a result, they found that, in addition to the GABA-degrading enzyme inhibitory effect, black garlic components also exhibit anti-erythraglutination activity (Figures 2(a) to (b)). When black garlic is used as an enzyme carrier, this anti-erythraglutination activity allows the enzyme to be transported to the body's internal organs along with red blood cells. This may be because the biological effects of the enzyme are exerted in these internal organs, resulting in a decrease in the amount of methylated nucleosomes in the blood (Figure 3). Here, methylated nucleosomes refer to nucleosomes released into the bloodstream after apoptosis that contain DNA methylation and histone methylation. It has been reported that cancer patients have more methylated nucleosomes than healthy individuals because this methylation inactivates tumor suppressor genes (Non-Patent Literature 6 and 7). This invention is based on the finding that ingesting an enzyme composition using black garlic as an enzyme carrier reduces methylated nucleosomes in the blood. The enzyme composition is formulated by blending aged plant enzyme liquid (specific gravity 1.10 to 1.20) with aged black garlic paste, which has anti-erythrocyte agglutination activity, in an equal to or five-fold weight ratio. To this, amla (a coenzyme) is added in an amount equal to half to one-quarter the weight ratio of the plant enzyme liquid, and an appropriate amount of oligosaccharides, an enzyme nutrient, is added to adjust the flavor, thereby creating an enzyme composition that reduces the amount of methylated nucleosomes (positively charged nucleosomes) in the blood. Specifically, it consists of 100 to 500 parts by weight of aged black garlic paste per 100 parts by weight of aged plant enzyme liquid (specific gravity 1.10 to 1.20), 50 to 25 parts by weight of the coenzyme amla (a coenzyme) per aged plant enzyme liquid (specific gravity 1.10 to 1.20), and an appropriate amount of oligosaccharides, an enzyme nutrient. Even when black garlic paste is added in an amount equal to or greater than that of the aged plant enzyme solution, no improvement in the anti-erythrocyte agglutination effect can be expected, and when the amount is less than 1 / 5, the anti-erythrocyte agglutination effect is insufficient. Therefore, the amount added was set to be between an equal amount and 1 / 5 of the amount. Amla (Yu Gan Zi), a coenzyme, even when added in an amount greater than half of the aged plant enzyme solution, no improvement in reactive oxygen species scavenging can be expected, and when the amount is less than 1 / 4 of the amount, it is insufficient. Therefore, the amount added was between half and 1 / 4 of the amount. On the other hand, since the enzyme composition of the present invention has enhanced DDS function, considering the usual single dose, half to 1 / 4 of the amount of Sparassis crispa powder was added to the aged plant enzyme solution to complete the second enzyme composition. (Preparation of enzyme compositions using aged black garlic as a carrier) The first enzyme composition consists of 100 to 500 parts by weight of aged black garlic paste per 100 parts by weight of aged plant enzyme liquid (specific gravity 1.10 to 1.20), 50 to 25 parts by weight of the complementary factor amla (yu gan zi) per aged plant enzyme liquid, and an appropriate amount of the enzyme nutrient oligosaccharide. Here, 1) the aged black garlic paste is made by fermenting raw garlic in a gradual aging process for approximately 30 to 60 days in an environment of 60-90% humidity and 40-90°C, and then processing the resulting black garlic into a paste. 2) As the aged plant enzyme liquid, commercially available Marumi Enzyme (liquid plant fermentation extract: specific gravity 1.12-1.13) from Kagoshima Prefecture was used. 3) As the coenzyme amla (Yu Gan Zi), a product manufactured by Shanghai Yuan Lu Jing Mao Co., Ltd. with approximately 300,000 SOD was used. Amla is reported to contain heavy metals, large amounts of SOD, 12 types of vitamins, 10 types of amino acids, 10 types of elements, linoleic acid, linolenic acid, organic selenium, tannins, etc., but its reactive oxygen species scavenging activity was particularly high, measured at 3.8 × 10⁶ by electron spin resonance (ESR) spectroscopy. 5 The evaluation was given in SOD units / g (Japan Food Research Laboratories analysis test report), ascorbic acid 3.3 × 10 5 It is noteworthy for being extremely high, equivalent to or even higher than [another example] (Japan Food Research Laboratories 2003). 、 As a specific example of the present invention, 10 parts by weight of Marumi enzyme solution (specific gravity 1.12) was mixed with 50 parts by weight of black garlic paste and 5 parts by weight of amla powder, and 35 parts by weight of oligosaccharide was added to this mixture to season it, thereby preparing and using the first enzyme composition.
[0014] The second enzyme composition consists of 100-500 parts by weight of aged black garlic paste per aged plant enzyme liquid (specific gravity 1.12), 50-25 parts by weight of coenzyme amla (Yu Gan Zi) powder per aged plant enzyme liquid (specific gravity 1.12), 50-25 parts by weight of Sparassis crispa powder per aged plant enzyme liquid (specific gravity 1.12), and an appropriate amount of oligosaccharide as an enzyme nutrient. Here, as a specific example, 18 parts by weight of Marumi Enzyme Liquid (product name), 35 parts by weight of black garlic paste (homemade), 5 parts by weight of amla (manufactured by Shanghai Yuan Green Trading Co., Ltd.), and 7 parts by weight of Sparassis crispa (lactic acid fermented Sparassis crispa powder manufactured by Daishoku DN Co., Ltd.) were kneaded together, and 35 parts by weight of oligosaccharide was added to season it to prepare the second enzyme composition.
[0015] The first enzyme composition was administered to patients E and D, whose immune function was thought to be weakened due to fatigue, and the second enzyme composition was administered to patients A, B, and C, whose immune function was weakened due to diseases such as cancer. Changes in the amount of methylated nucleosomes were observed over 90 days.
[0016] (Measurement of positively charged nucleosomes (methylated nucleosomes)) The effect of the enzyme composition according to the present invention is measured by the method for quantifying positively charged nucleosomes released into the blood after apoptosis, as described in WO2021 / 132576A1. Fragmented nucleosomes captured with single-wavelength excitation light from a laser or excitation light of a constant wavelength width selected by a filter are excited, and the total area of the fluorescent colonies above a predetermined threshold is measured. Equipment used: Keyence Corporation, Fluorescence Microscope BZ-X710 Light source: 80W metal halide lamp Fluorescence filter: BZ-X filter DAPI (460±25nm) Analysis software: BZ-X Analyzer a) Selective capture of positively charged nucleosomes: Figure 4A Measurement substrate having a plasmonic metal mesocrystal region showing surface negative charge in a sample: A proteo-chip (Fig. 4A(1)) is brought into contact with a specimen prepared by directly applying or diluting a body fluid or a culture solution containing cells (Fig. 4A(2)), and a protein conjugate (nucleosome) showing positive charge in the specimen is captured as a disease-related substance by the plasmonic metal mesocrystal through charge capture (Fig. 4A(3)). b) Fluorescent image acquisition step: Fig. 4B (1) Set the proteo-chip with nucleosomes attached thereto on a fluorescence microscope, determine the measurement positions (X and Y axes) of the chip while observing a bright-field image, and click the autofocus button to focus the chip (Z axis, focus). Switch the measurement setting to the BZ-X filter DAPI and start the measurement of the fluorescent image. This is a step of irradiating the protein conjugate captured on this plasmonic metal mesocrystal (with a diameter of about 8 mm) with excitation light, enhancing the autofluorescence of the captured protein conjugate by the surface plasmon enhancement effect, and acquiring a fluorescent colony as a fluorescent image (Fig. 4B). c) Fluorescent colony selection step: Fig. 4C This is a step of binarizing the luminance of fluorescent colonies within the analysis range (with a diameter of 5 mm) and selecting fluorescent colonies with a luminance above a predetermined threshold. d) Calculation step: Calculate the total area value (Fig. 4C) of the selected fluorescent colonies above a predetermined threshold. Here, substances with strong fluorescence (blue deposits, with a binarization threshold of 13 or more based on the luminance value under the following measurement conditions) are selected, and their area values are calculated (unit: μm 2 ). Classify and determine the area value into three levels: A for low cancer risk when it is 0 to 19,999, B for observation required when it is 20,000 to 29,999, and C for having cancer risk when it is 30,000 or more.
[0017] (Relationship between methylated nucleosome and disease) (Example 1): Mr. HI (prostate cancer: PSA 7.9 in November 2022, signs of prostate cancer detected by MRI in May 2023: positively charged nucleosome amount: average 28,000 points, and in August 2023: malignant tumor detected in 1 out of 12 biopsies) underwent 29 proton beam irradiation treatments five times a week starting in February 2024. As a result, four months after the completion of treatment, his PSA was below 0.01 and his positively charged nucleosome amount averaged 5,000 points. In other words, the amount of autofluorescence of positively charged nucleosomes decreased along with the therapeutic effect on prostate cancer. This indicates that cancer cells were eliminated by radiation therapy, and as a result, methylated nucleosomes in the blood decreased.
[0018] (Effect of the enzyme composition according to the present invention on reducing positively charged nucleosomes) (Example 2) The black garlic-based enzyme composition according to the present invention was divided into two types: the first enzyme composition and the second enzyme composition. The first enzyme composition was administered to healthy individuals D and E as a fatigue recovery supplement, while the second enzyme composition was administered to cancer patients A, B, and C with a positive charge of 30,000 or more. The dosage was one teaspoon once daily for individuals D and E who desired fatigue recovery, and one teaspoon three times daily for three months for cancer patients A, B, and C. The amount of positively charged nucleosomes was compared before ingestion of the black garlic-carrying enzyme composition of the present invention and after three months. It appeared that the effect on fatigue recovery began after one week, but the effect was slow for all patients except prostate cancer patient A (see Figure 2). Mr. A (66 years old: high risk of prostate cancer): Administered 1 teaspoon of the second enzyme composition three times a day. Autofluorescence level decreased from 30,000 to 23,000 after 90 days (significant effect). Mr. B (70 years old: suspected of having cancer): Administered 1 teaspoon of the second enzyme composition three times a day. Autofluorescence level: over 40,000 → decreased to 35,000 after 90 days (little effect). Mr. C (56 years old: high risk of colon cancer): Administered 1 teaspoon of the second enzyme composition three times a day. Autofluorescence level decreased from 35,000 to 26,000 after 90 days (little effect). Mr. D (45 years old: high fatigue level): Administered 1 teaspoon of the first enzyme composition once a day. Autofluorescence decreased from 25,000 to 15,000 after 2 weeks, and then to 10,000 after 4 weeks. Mr. E (50 years old: high fatigue level): Administered 1 teaspoon of the first enzyme composition once a day. Autofluorescence decreased from 25,000 to 15,000 after 2 weeks, and then to 10,000 after 4 weeks. The autofluorescence level was calculated using the average of two approximate measurements out of three (with two significant figures).
[0019] Based on the results of the clinical trials described above, it appears that the relationship between cancer patients and their recovery can be determined by the amount of autofluorescence of methylated nucleosomes, as seen in Example 1. For fatigue recovery D and E, a correlation was observed between the degree of fatigue and the amount of autofluorescence of methylated nucleosomes, indicating a significant effect. On the other hand, while it appears to be effective in reducing positively charged nucleosomes (methylated nucleosomes) in prostate cancer and colorectal cancer patients, little effect was observed in severely ill patients.
[0020] As is clear from the above explanation, according to the present invention, the reduction of methylated nucleosomes (positively charged nucleosomes) in the blood can be achieved by ingesting an enzyme composition prepared by adding amla (Yu Gan Zi) to black garlic paste as an enzyme carrier. The exact mechanism of this reduction of methylated nucleosomes is unclear, but it is thought to be due to the anti-erythrocyte agglutination effect of black garlic, which improves the DDS function of coenzymes along with enzymes from capillaries, and the synergistic effect of the reactive oxygen species scavenging effect of the coenzymes in black garlic and amla and the coenzyme components. Therefore, by preparing an enzyme composition using black garlic paste as a carrier, a specified amount of aged plant enzyme liquid, and a specified amount of amla to the aged plant enzyme liquid, the reduction of methylated nucleosomes according to the present invention can be achieved. Thus, it is easy for those skilled in the art to implement the present invention without departing from the gist of the invention by adding other components to the enzyme composition of the present invention.
Claims
1. An enzyme composition comprising aged plant enzyme liquid, aged black garlic paste in an equal to or five times the weight ratio, amla (yu gan zi) powder in an equal to or one-fifth the weight ratio of the aged plant enzyme liquid, and an appropriate amount of oligosaccharide, characterized by having an effect of reducing methylated nucleosomes. However, here, "aged plant enzyme liquid" refers to a liquid substance with a specific gravity of 1.10 to 1.20 containing plant enzymes produced through a drying → fermentation → aging process, which includes plant sources such as wild grasses, wild grass stems and branches, fruits, and grains used for enzyme extraction. It also refers to a substance that has been dried and then dissolved or dispersed in various solvents such as water and carbonated water, as well as substances containing the dissolution or dispersion medium. Furthermore, "aged black garlic paste" refers to garlic produced by a fermentation process in which raw garlic is aged in stages under conditions of 60-90% humidity and 40-90°C, or by a Maillard reaction (aminocarboxyl reaction) process, and includes products that are blackened or browned by the fermentation process. In addition, "amla" refers to the dried powder of the fruit of a deciduous tree of the genus Phyllanthus in the family Phyllanthaceae, which has a high SOD value of 100,000 or more, preferably 300,000.
2. Furthermore, the enzyme composition according to claim 1, comprising half to one-quarter by weight of dried Sparassis crispa powder relative to the matured plant enzyme liquid.
3. The enzyme composition according to claim 1 or 2, wherein the aged black garlic paste comprises aged black garlic blended with other components having an anti-erythrocyte aggregation effect.
Citation Information
Patent Citations
Novel black garlic extract from separated garlic bulbs and preparation method thereof
JP2021108652A
WO2021/1323576