JP2006083104A - FOOD ADDITIVE FOR PREVENTING IgA NEPHROPATHY - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a food additive for preventing IgA nephropathy which eliminates IgA in the blood of a patient of IgA nephropathy or a sugar chain abnormal type IgA from inside of the body, and its treating method. <P>SOLUTION: The food additive for preventing IgA nephropathy adjusts the IgA concentration in the blood of a patient of IgA nephropathy to an appropriate value to maintain it by taking in a food alone, and its treating method is described. The food additive for preventing IgA nephropathy is constituted of "an extract of jackfruit seeds" containing "jacalin and/or a jacalin derivative" which is specifically bound to IgA, and the food is suitably used for preventing or treating IgA nephropathy. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a novel food additive for treating and / or preventing IgA nephropathy containing jacarin and / or a derivative thereof that binds to immunoglobulin A (IgA) in blood or tissue fluid, and IgA nephropathy using the same. It relates to a treatment method. The present invention forcibly and selectively removes or deactivates IgA from the blood or tissue fluid of an IgA nephropathy patient by ingestion as a food, thereby preventing an increase in the blood concentration of IgA and adjusting / maintaining it to an appropriate concentration. It is suitably used for the purpose of preventing the onset or worsening of IgA nephropathy.

  Currently, the total number of patients undergoing dialysis therapy in Japan due to end stage renal failure exceeds approximately 230,000. In addition, about 10,000 new patients with chronic renal failure each year are required to introduce artificial dialysis treatment, and in many cases it is necessary to maintain dialysis treatment until death. While the total number of patients with renal failure requiring such dialysis treatment is increasing year by year, there is currently no radical treatment other than organ transplantation treatment. However, transplantation of living tissue has many important medical and social problems such as immune rejection and donor shortage, and significant progress cannot be expected in the future. The main causative diseases that lead to renal failure include diabetic nephropathy, hypertensive nephropathy, polycystic kidney disease, etc., especially chronic glomerulonephritis, more than 35% of the total, and 40 to 40 of chronic glomerulonephritis. 50% is occupied by IgA nephropathy.

  IgA nephropathy is a disease characterized by pathological findings of granular deposition of IgA (mainly IgA1) and complement C3 in the glomerular mesangial region, and a high serum IgA concentration is present in about 50% of affected patients. It has been reported that IgA-type immune complexes are present in the bloodstream. If this state continues for many years, IgA is deposited on the glomeruli and thus the kidney function is lost (Non-patent Document 1).

  IgA nephropathy is a disease concept proposed by Berger et al. In 1969, but the cause of this disease is still unclear even after 30 years. Clinically, there are few clinical symptoms other than proteinuria and hematuria, and it is also a disease that is difficult to notice the progression of the disease, and there is no general method other than the method by renal biopsy, so the discovery may be delayed Many.

  Although the pathogenesis of IgA nephropathy has not been fully elucidated, the reported mechanism is mainly due to foreign antigens that have entered the body, mainly in the upper respiratory tract, submucosal lymphocytes and plasma cells in the digestive tract IgA involved in mucosal immunity is produced, and IgA is highly selectively associated with an IgA binding-related receptor on the surface of mesangial cells (Non-patent Document 2), and the induction of inflammation associated therewith has been proposed. Pathologically, the main mechanism of glomerular injury after IgA deposition is considered to be a sclerosing lesion caused by proliferation of mesangial cells and subsequent accumulation of extracellular matrix proteins in the glomeruli. In the process, the involvement of platelet-derived growth factor (PDGF) and transforming growth factor (TGF-β) is considered to be important, but details are unknown.

  IgA is classified into two subtypes called IgA1 and IgA2, and IgA1 has five oxygen-binding sugar chains bound to a region called a hinge part, while this oxygen-binding sugar is bound to the hinge part of IgA2. It is known that no chain exists.

  It is known that IgA deposited on glomerular mesangial cells of patients with IgA nephropathy is mainly IgA1. There is still no clear conclusion as to whether this IgA1 was produced by the upper respiratory tract, submucosal lymphocytes or plasma cells of the digestive tract system, or by the bone marrow. However, since most of the IgA produced in the body is made from IgA-type plasma cells of mucosal tissue, it is considered that IgA1 of patients with IgA nephropathy is also highly likely to be produced under the mucosa.

Moreover, normal type IgA1 usually has a sialic acid-galactose β1-3 linked N-acetylgalactose sugar chain at the hinge, but IgA1 in the blood of IgA nephropathy patients has sialic acid as its leading molecule. It is said that the ratio of the asialo type which does not do is high (nonpatent literature 3). In particular, it has been reported that these abnormal sugar chains of IgA1 have the property of being easily bound to each other, and further, high binding to the mesangial cell surface receptor and the resulting effect on the cell cycle are beginning to be pointed out. (Non-Patent Document 2)).

Several methods have been developed for diagnosing IgA nephropathy using the knowledge about IgA1 sugar chain abnormality. For example, a diagnostic method for IgA nephropathy using the fact that the number of sugar chains bound to the hinge part of IgA1 in IgA nephropathy patient plasma is higher than IgA1 in non-IgA nephropathy patient plasma by Tanaka, Nishikido, and Hiki et al. ), Hiki, Tanaka, and Nishikido et al., An invention of a method for diagnosing IgA nephropathy by detecting a difference in binding ability between IgA1 molecules (JP-A-9-311132). Moreover, as an example of the invention in the publication, etc., as a material for separating IgA1 from serum, blood and tissue fluid, jakarin-agarose in which “jacarin”, which is a kind of lectin, is fixed to agarose, is used. This is based on the method using “Jakarin” by Roque-Barreria et al. However, these inventions provide a method for diagnosing IgA nephropathy and a diagnostic kit thereof, and do not provide a method for preventing or treating IgA nephropathy by ingestion as a food or a drug.

Japanese Patent Laid-Open No. 10-111291 JP-A-9-311132

Conley, M.E., et al., Journal of Clinical Investigation, 66, 1432, 1980 Y. Wang et al. Clin Exp Immunol, 136, 168-175, 2004 Iwase, Hitoo et al., Journal of Biochemistry, 120, 92, 1996 Journal of Immunology, 134, 1740-1743, 1985

  As described above, the cause of IgA nephropathy has not been clearly elucidated yet, but there is no particularly effective method for preventing or treating IgA nephropathy, but it has anti-inflammatory and immunosuppressive effects. Therefore, corticosteroid therapy is considered promising. However, in order to expect the effect of steroid therapy in cases where proteinuria is 1.0 g / day or more, a treatment period of 2-3 years or more is required, and for IgA nephropathy, at least 10 years are required to judge the treatment effect. It is said that it is necessary. In addition, steroids are known to have many side effects. Serious side effects include infections, peptic ulcers, diabetes, psychiatric disorders, glaucoma, aseptic osteonecrosis, osteoporosis, arteriosclerosis, thrombosis, and the risk of complications is high. From the above, prevention or treatment methods for IgA nephropathy with few side effects other than steroids have been desired.

  An object of the present invention is to provide a food additive that adjusts and maintains an IgA concentration in the blood of an IgA nephropathy patient by an intake only by food, and to provide a method for preventing or treating the onset of IgA nephropathy. It is in.

Regarding IgA's involvement in IgA nephropathy, as described above, IgA or abnormal sugar chain type IgA1 is deposited in the glomerular glomerulus due to the presence of IgA nephropathy patient's blood and tissue fluid at a high concentration. Or it may be an indirect cause and cause glomerulonephritis.
In addition, the present inventors have immobilized jacalin and / or its derivatives on a water-insoluble carrier as an adsorbent for blood purification intended to control the progression of disease by adjusting the IgA concentration in the blood. Have been found to be suitable (Japanese Patent Application No. 2003-1224036 “Adsorbent for blood purification for the treatment of IgA nephropathy”). However, the method for adjusting the IgA concentration using the blood purification material is efficient from the viewpoint of physical burden in consideration of the necessity of a blood circulation device comparable to the artificial dialysis treatment and the time constraint of the patient required for the treatment. The point that was difficult to say was the method.

  Based on the above findings, the present inventor has conducted extensive research for the purpose of reducing the physical burden of the patient and effectively providing a method for preventing or treating IgA nephropathy by adjusting the IgA concentration in the blood. As a result, the present inventors have found that a food additive containing jackfruit seed extract or jacalin and / or a derivative thereof contained therein is suitable, and completed the present invention.

That is, the present invention is a food additive having an effect of improving IgA nephropathy, and is an aqueous extract of jackfruit seeds mainly composed of jacarin and / or jacarin derivatives. Further, the jacalin and / or jacarin derivative is a jacalin complex having a jacarin molecular number of 1 to 10, and the molecular weight thereof is 50 to 500 KDa, and / or the jacalin and / or the derivative thereof is A degradation product of a jacalin complex, characterized in that its molecular weight is 15 to 50 KDa.
And the form of the water extract of the seed of this jackfruit is a powder form or aqueous solution form, It can be orally ingested by mixing with another foodstuff.
Furthermore, the present invention provides an IgA nephropathy prophylaxis characterized by removing IgA from blood and / or tissue fluid of a patient by orally administering the water extract of the jackfruit seed to an IgA nephropathy patient. And / or methods of treatment.

  The food for preventing or treating IgA nephropathy containing the “jack fruit seed extract” of the present invention has the effect of preventing inflammation of the kidney glomerulus and suppressing the induction of inflammation by adjusting the blood IgA concentration. It is done.

  Embodiments of the present invention will be described in detail below, but the technical scope of the present invention is not limited by the following embodiments, and various modifications can be made without changing the gist thereof. Can do. Further, the technical scope of the present invention extends to an equivalent range.

“Jakarin” used in the present invention is a fruit of the mulberry family Jack fruit (Artocarpus
heterophyllus: A kind of plant lectin contained in the seed of the Japanese name "Haramitsu (palamitsu)", which is obtained by extraction and purification. Jackfruit is native to India and Thailand and is widely distributed in the tropics. The fruit itself is large and can reach 40-50 kg. The fruit is not particularly limited, but is mainly contained in Jack fruit because it is derived from its name, and it is easy to extract. “Jakarin” usually accounts for 50% or more of the seed protein of jackfruit (Non-patent Document 6). The homologous plants include breadfruit and copal honey, and extraction from these seeds is also possible.

  “Jakarin” is known as a lectin protein that recognizes the sugar chain of IgA, and its recognition sugar chain is not limited to one type, but it is an oxygen-linked and normal type IgA1 sugar chain structure of sialic acid galactose β1-3 linked N Acetyl galactose or galactose β1-3N acetylgalactose (abnormal sugar chain) is known as a high affinity structure. (Non-patent document 7)

S. Kabir et al., Comparative Immunology, Microbiology and Infectious Diseases, 16, 153, 1993 S. Kabir et al. Journal of Immunological Methods 212, 193-211, 1998

  There are few human serum proteins that have an oxygen-linked sugar chain, that is, a galactose β1-3 linked N-acetylgalactose sugar chain that is bound to the hydroxyl group of serine or threonine, which is an amino acid in the protein molecule. N-linked type that binds to the amino group of asparagine. IgA1 molecules have oxygen-linked sugar chains, both normal and abnormal, and are thought to specifically recognize and bind to “jacarin”.

“Jakarin” is a glycoprotein with a molecular weight of about 65 KDa consisting of a subunit structure with a molecular weight of about 15 KDa called four α chains and a molecular weight of about 2.1 KDa called four β chains. The “jacarin” in the present invention is obtained by extracting jackfruit seeds with water at a low temperature and purifying the extract. At this time, a method in which jackfruit seeds are finely ground and then extracted with water is generally used. However, the method is not necessarily limited to this, and a method of squeezing seeds in an aqueous solution is also used.
The purification is generally performed by separating the water extract from the water-insoluble matter by filtration, but is not necessarily limited thereto.
The jackfruit seed extract / purified product obtained in this way contains jacarin as the main component and also contains carbohydrates, vitamin A and vitamin C.

  Such “jacarin” may be a single molecule, but its derivative (“jacarin complex” composed of about 1 to 10 molecules of “jacarin” and molecular weight of 50 to 500 KDa and / or hydrothermal treatment of the jacalin complex. It may be a “jacarin degradation product” having a molecular weight of 10 to 50 KDa), and even if it is a mixture, there is no significant difference in the effect as a food additive.

  The jackfruit seed extract / purified product of the present invention is supplied in the form of powder or aqueous solution as a food additive. The powder form is generally obtained by freezing / drying the extract / purified product. The aqueous solution can be obtained by extracting or purifying jackfruit seed itself or by dissolving the above powder in an aqueous solution.

These powdered or aqueous food additives are used by adding to various foods. Specifically, for example, confectionery such as candy, chewing gum, jelly, and cookies, confectionery bread, and beverages such as mineral beverages, lactic acid bacteria beverages, and alcoholic beverages.
The dosage of the “jack fruit seed extract” of the present invention is 1 to 100 g, preferably about 5 to 50 g per day for an adult, and is 0 per day for an adult in terms of “jacarin complex or jakarin degradation product”. 0.1 to 10 g, preferably about 0.5 to 5 g. Although the effect when many doses are observed, the IgA concentration-regulating effect depending on the dose is not necessarily expected. Moreover, when there is little dosage per day, there exists a possibility that the IgA density | concentration adjustment effect cannot be anticipated.

  Examples of food molding binders include sucrose, glucose, sucrose, starch, ethylcellulose, and lactose that are commonly used in the field of pharmaceuticals and foods. Carboxymethylcellulose, gellan, carboxymethylgellan, gellan sulfate, gelatin, sodium alginate, hydroxypropylcellulose and the like. As the surfactant, polyoxyethylene alkyl ether, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene propylene glycol monofatty acid ester, phospholipid, fatty acid, ethylene glycol polyhydric alcohol and the like are preferably used.

By the way, when an IgA nephropathy patient ingests an aqueous extract of jackfruit seed mainly composed of jacarin and / or a jacalin derivative according to the present invention, an IgA concentration increase in the blood and tissue of the IgA nephropathy patient is increased. The mechanism of suppression is considered as follows.
(1) Direct adsorption / removal effect in the gastrointestinal tract Immunoglobulin A (IgA) in blood and body fluids is mainly produced in the intestinal epithelial cells and then secreted into the gastrointestinal system or blood. By ingesting Jackfruit seed extract as a food, non-absorbable and non-digestible jacarin and / or its derivatives bind to IgA at the intestinal epithelial site in the digestive tract and inactivate or insolubilize it. It is secreted and absorbed into the body, and finally discharged from the digestive tract as stool. As a result, the blood concentration of IgA is prevented from increasing, adjusted to and maintained at an appropriate concentration, and the onset or worsening of IgA nephropathy is prevented.
(2) Indirect effects after absorption in the circulatory system When jacalin and / or its derivatives partially absorbed in blood bind to IgA in the blood, the mesangial cell surface in the glomerulus or the site of IgA production The structure of the IgA binding site to a certain intestinal epithelial cell surface part is inactivated. As a result, the tissue deposition phenomenon of IgA in the blood circulatory system is prevented, the subsequent induction of the renal inflammatory reaction is suppressed, and as a result, the onset or worsening of IgA nephropathy is prevented. The IgA jacarin complex that has escaped deposition is degraded and removed by the normal metabolic system (liver).

  Hereinafter, the present invention will be described in detail with reference to examples. However, the method shown below is used in the operation confirmation, and is not limited thereto.

<IgA nephropathy model animal used for evaluation of prevention effect of IgA nephropathy>
In order to verify the effect of the present invention, an IgA nephropathy model (HIGA) mouse (Japan SLC Mouse Co., Ltd.) was used. The HIGA mouse is a mouse characterized by high-concentration IgA in the ddy mouse system, and is known as a model animal for IgA nephropathy, and is widely used for IgA nephropathy research (for example, Kidney Int, 50, 1946-1957, 1995). Year).

<IgA nephropathy model mouse blood IgA concentration measurement method>
The IgA concentration in the serum of an IgA nephropathy model mouse was quantified using an ELISA method. Goat anti-mouse IgA (manufactured by Funakoshi) is used as the primary antibody stock solution, and Goat anti-mouse IgA HRP conjugated (manufactured by Funakoshi) is used as the secondary antibody stock solution. 7 samples were prepared and used in the range of 250 ng / ml-7 ng / ml using (IgA) (Funakoshi). As a primary antibody solution, 0.1 ml of the antibody stock solution is dissolved in 10 ml of 0.05 M NaCO ₃ -HCl buffer (pH 9.6), diluted, and then added in 0.1 ml portions to a 96-well ELISA immunoplate (manufactured by Nargen Nunk). Let stand for 90 minutes. Thereafter, the solution was removed, washed with 0.05 M Tris-HCl (pH 8) buffer containing 0.14 M NaCl and 0.05% Tween 20, and air-dried to obtain an ELISA plate for measurement.
The mouse serum sample to be measured was diluted 1/20000 with 0.05 M Tris-HCl (pH 8) buffer containing 0.14 M NaCl and 1% bovine serum albumin (BSA). Add 1 ml and allow to penetrate for 60 minutes. At the same time, add each of the seven standard solutions in separate holes. After stirring, the solution was removed and washed several times with 0.05 M Tris-HCl (pH 8) buffer containing 0.14 M NaCl and 0.05% Tween 20, and then the secondary antibody solution diluted 1/100 was added to 0. Add 2ml each to the hole and allow to penetrate for another 60 minutes. After removing the secondary antibody solution and washing, 0.1 ml each of a solution obtained by adding 1 tablet of OPD tablet (manufactured by Wako Pure Chemical Industries, Ltd.) and 0.005 ml of H ₂ O ₂ to 12 ml of citrate buffer was added. Then, after standing for 10 minutes to cause color development, 0.1 ml each of 1N sulfuric acid aqueous solution was added to the hole to stop color development, and the absorbance at 450 nm was measured with a plate reader (manufactured by Bio-Rad). The concentration was calculated in light of the prepared calibration curve.

<Method for measuring blood albumin concentration in IgA nephropathy model mouse>
The albumin concentration in the serum of IgA nephropathy model mouse was quantified using ELISA method (commercially available kit: manufactured by Exocell). Rabbit anti-mouse Album (manufactured by Funakoshi) and secondary antibody stock anti-rabbit HRP conjugate (manufactured by Funakoshi) are used as the primary antibody stock solution, and Human serum Calibrator (IgA) (Funakoshi) is used as a standard solution for determining the concentration. Measured according to the kit manual.

<IgA staining method of tissue specimen>
In order to evaluate the preventive effect of the product of the present invention, kidney glomerular tissue sections and intestinal epithelial tissues of the HIGA mice used were prepared, and the IgA deposition status was confirmed using fluorescent immunostaining. The immunostaining method was performed by a known method. For the staining, mouse anti-human IgA was used as the primary antibody, and mouse anti-human IgA FITC conjugated was used as the secondary antibody. This indicates that IgA is present at a location where fluorescence by FITC is detected. Further, it was confirmed from the secondary antibody staining (control) without the primary antibody treatment that no portion other than IgA was detected.

<Method for Preparing “Jakarin Complex” and “Jakarin Degradation Product”>
Jack fruit seeds (the size of one seed is 3.5 cm in the long axis direction and 2 cm in the short axis direction) are separated from the pulp, and the skin covering the seeds is removed and finely crushed with a food processor or the like. A 100 mM Tris-HCl buffer solution (pH 7) is added and stirred at 4 ° C. for 24 hours to obtain a crude jacalin solution. The insoluble part was removed by filtration, and then centrifuged (3000 rpm, 30 minutes), and only the supernatant part was recovered. Further, the solution is filtered through a membrane filter (made by Millipore) having a pore size of 0.22 micrometers, and the solution is put into a tube made of a regenerated cellulose dialysis membrane (removed molecular weight of 6000 or less: made by Spectrapore), and against deionized water Dialysis was performed for 48 hours or more, and then lyophilized to obtain a “jacarin complex”.

The “jacarin degradation product” was obtained by adding 100 ml of water to 1 g of the “jacarin complex” prepared by the above-described method, boiling the solution for 5 minutes, and then rapidly cooling and freeze-drying.
The molecular weights of the “jacarin complex” and “jacarin degradation product” obtained as described above were confirmed using SDS polyacrylamide gel electrophoresis. The method was performed by a known method. As electrophoresis conditions, 7.5% (w / w) polyacrylamide gel (manufactured by Biorat) was used for “jacarin complex” and 15% (w) for “jacarin degradation product”. / W) Performed using polyacrylamide gel (Biorat). The protein band was detected by staining with Coomassie Brilliant Blue (Wako Pure Chemical Industries), and the molecular weights of “Jakarin Complex” and “Jakarin Pyrolysate” were calculated from the relative mobility from the molecular weight marker (Bio Rat). As a result, the “jacarin complex” has 1 to 10 “jacarin” molecules, the molecular weight is 50 to 500 KDa, and the “jacarin degradation product” is derived from 15 to 50 KDa “jacarin” in addition to “jacarin complex”. It was a mixture containing degrading molecules.

<Preparation of "Jack fruit seed extract">
Jack fruit seeds (one seed is 3.5cm in the long axis direction and 2cm in the short axis direction) are separated from the pulp, except for the skin covering the seeds, and a small amount of deionized water is added to the food processor, etc. Crush finely. Thereafter, it was freeze-dried to obtain “Jack Fruit Seed” powder. 350 mg of dry powder was obtained from 1 g of seeds. Add 200 ml of deionized water to 200 mg of “Jack Fruit Seed” powder, stir for 10 minutes, filter through a membrane filter with a pore size of 0.22 μm, and freeze-dry again to obtain “Jack Fruit Seed Extract” It was. About 300 mg of powder was obtained from 1 g of “Jack Fruit Seed” powder. From the above, it was found that jackfruit seeds had a composition of about 65% water, about 10% water extract and 25% water insoluble matter. “Jakarin” and “Jakarin complex” are the main components of this water extract, and other ingredients in “Jack Fruit Seed Extract” include carbohydrates, vitamin A and vitamin C.

<Preparation of “Jackin Seed Extract” Containing “Jakarin Degradation Products”>
Add 200 ml of deionized water to 200 mg of “Jack Fruit Seed” powder, heat to 100 ° C., stir for 10 minutes, quench rapidly to 4 ° C., filter through a 0.22 micrometer pore size membrane filter, and freeze-dry. “Jackin seed extract” containing “jacarin degradation product” was obtained. About 250 mg of powder was obtained from 1 g of “Jack Fruit Seed” powder.

  (1) 1 g of “Jack fruit seed extract” powder is added to 100 g of powdered normal mouse feed, mixed, 10 ml of deionized water is added, and the mixture is further mixed. Create a feed shape and dry it aseptically in a clean bench. The “Jack fruit seed extract” formulated feed prepared as described above was administered to 12 HIGA mice at 11 weeks of age up to the age of 21 weeks (feed administration group). In addition, the tap water which does not contain a "jack fruit seed extract" was used for the drinking water to a feed administration group.

  (2) 1 g of “Jackfruit Seed Extract” powder is added to 100 ml of deionized water, mixed at room temperature, and then filtered to remove unwanted materials with a paper filter, using a 0.45 micron filter. The drinking water for HIGA mice was used. The “Jack fruit seed extract” blended drinking water prepared as described above was fed to 12 HIGA mice at 11 weeks of age until the maximum of 21 weeks of age (drinking water administration group). In addition, the feed for the drinking water administration group was a normal feed for mice that does not contain “Jackfruit seed extract”.

(3) As a control group, feed for normal mice and tap water was administered to 12 HIGA mice at 11 weeks of age up to the age of 21 weeks (control group).
As evaluation items, the average body weight of HIGA mice in each group, the daily intake of feed and the intake of drinking water were measured daily. In addition, blood was collected from the tail of each HIGA mouse once a week (starting from 12 weeks of age), and the serum IgA concentration and serum albumin concentration were measured. Further, every 4 weeks, 3 animals were sacrificed and tissue sections of kidney glomeruli and intestinal epithelial tissue were prepared, and IgA immunostaining was performed to observe IgA tissue deposition behavior.

<Result>
The transition of the average body weight of 6 animals from 11 to 21 weeks of age is shown in FIG. 1 (◯: control group, □: feed administration group, ▲: drinking water administration group). The tendency of weight gain in the control group was slightly different compared to other “Jackfruit seed extract” administration groups. The transition in body weight was almost the same between the “Jack fruit seed extract” administration groups, and an average of 5 to 6 g was increased in each group throughout the administration period.

  The change in feed intake is shown in FIG. 2 (◯: control group, □: feed administration group, ▲: drinking water administration group). Regarding feed intake, although the intake amount of the “Jack fruit seed extract” mixed feed administration group is larger than that of the other groups, there is no relationship with administration time or weight gain. All groups received an average of 4-8 g of feed per day. In the “Jack fruit seed extract” mixed feed administration group, about 4 to 8 mg of “Jakarin” or “Jakarin derivative” was ingested per day. Considering that the average body weight of HIGA mice is 30 to 40 g, it is considered that it corresponds to intake of about 4 to 10 g in terms of weight per adult.

  The transition of drinking water intake is shown in FIG. 3 (◯: control group, □: feed administration group, ▲: drinking water administration group). With regard to drinking water intake, all groups consume an average of 4-8 g of drinking water per day, and the “Jack Fruit Seed Extract” combination drinking water administration group receives about 4-8 mg of “jacarin” or “ This means that the “Jakarin derivative” was ingested. Considering that the average body weight of HIGA mice is 30 to 40 g, it is considered that it corresponds to intake of about 4 to 10 g in terms of weight per adult.

  The transition of the average serum IgA concentration in the blood of HIGA mice in each group is shown in FIG. 4 (◯: control group, □: feed administration group, ▲: drinking water administration group). The concentration measurement value at each week was divided by the serum concentration at 12 weeks of age and evaluated as the rate of increase in serum concentration from 1 week after the start of administration (serum IgA concentration / serum IgA concentration at 12 weeks of age). That is, 1 week after administration was normalized as 1. The serum IgA concentration at 12 weeks of age in each group was 1.14 ± 0.57 mg / ml in the control group, 2.36 ± 0.54 mg / ml in the feed group, and 1.87 ± 0 in the drinking water group. .43 mg / ml. Compared with the control group, the “Jack fruit seed extract” mixed feed and the “Jack fruit seed extract” drinking water administration group clearly showed an effect of suppressing an increase in serum IgA concentration in about 2 weeks after the start of administration. It was.

  The transition of the average serum albumin concentration in the blood of HIGA mice in each group is shown in FIG. 5 (◯: control group, □: feed administration group, ▲: drinking water administration group). The concentration measurement value at each week was divided by the serum concentration at 12 weeks of age, and the rate of increase in serum concentration from 1 week after the start of administration (serum albumin concentration / serum albumin concentration at 12 weeks of age) was evaluated. That is, 1 week after administration was normalized as 1. The serum albumin concentration at 12 weeks of age in each group was 0.578 ± 0.01 mg / ml in the control group, 0.574 ± 0.01 mg / ml in the feed administration group, and 0.564 ± 0 in the drinking water administration group. 0.02 mg / ml. There is no significant difference between the “Jack fruit seed extract” mixed feed, the “Jack fruit seed extract” drinking water administration group and the control group. That is, there is no influence on the change in serum albumin concentration in the administration of IgA nephropathy preventing food.

  A tissue IgA-stained image of renal glomerular tissue of HIGA mice is shown in FIG. FIG. 6-1 shows renal glomerular tissue at 4 weeks (15 weeks old) from the start of administration in the control group, and FIG. 6-2 shows 8 weeks (19 weeks old) from the administration start of the control group (observation magnification 400). Times). It can be seen that the IgA-stained portion increases within the mesangial region as the age increases, and that an IgA deposition phenomenon occurs. Fig. 6-3 shows the fourth week (15 weeks old) from the start of administration of the "Jack fruit seed extract" mixed feed, and Fig. 6-4 shows the eighth week (19 weeks) after the start of the "Jack fruit seed extract" mixed feed. (Age) renal glomerular tissue (observation magnification 400 times). It was observed that the amount of deposition at 8 weeks was suppressed as compared to the control group.

  FIG. 7 shows a tissue IgA-stained image of the intestinal epithelial tissue of the HIGA mouse. Fig. 7-1 shows the intestinal epithelial tissue at 4 weeks (15 weeks old) of administration of the control group, and Fig. 7-2 shows the intestinal epithelial tissue at 12 weeks (23 weeks of age) after administration of the control group (observation magnification 400 times). . The IgA-stained portion was remarkably observed around the lymphoid cells in the epithelial villous tissue, and it was observed that IgA production / accumulation increased with age. 7-3 shows the 4th week (15 weeks of age) from the start of administration of the “Jackfruit seed extract” mixed feed, and FIG. 7-4 shows the 12th week (23 weeks of the start of the “Jackfruit seed extract” combined feed administration). (Age) intestinal epithelial tissue is shown (observation magnification 400 times). It was observed that the detected amount at 12 weeks was suppressed as compared with the control group.

  From the above results regarding the difference in dosage form as “Jack fruit seed extract” mixed feed and mixed drinking water for HIGA mice, there is no significant difference in feed and drinking water intake, and the blood IgA concentration is decreased. Regarding the effect, the increase rate of the IgA concentration in the serum of the “Jack fruit seed extract” administration group was clearly suppressed as compared with the control group. Regarding the change in blood albumin concentration, there was no difference between the groups, that is, only the IgA concentration was effective. Regarding the IgA deposition and production / accumulation in the tissue, the administration group clearly showed an inhibitory effect as compared with the control group. From the above results, the “Jack fruit seed extract” -containing food (feed or drinking water) according to the present invention selectively decreases the blood IgA concentration only by oral administration, and IgA is deposited in the tissue. It is considered that an IgA nephropathy preventing effect or a therapeutic effect is observed.

It is a figure which shows the transition ((circle): control group average, (square): feed administration group, (triangle | delta): drinking water administration group) of the weight change of a HIGA mouse | mouth. It is a figure which shows the transition ((circle): control group average, (square): feed administration group, (triangle | delta): drinking water administration group) of the feed intake of a HIGA mouse | mouth. It is a figure which shows transition ((circle): control group average, (square): feed administration group, (triangle | delta): drinking water administration group) of the drinking water intake of a HIGA mouse | mouth. It is a figure which shows the IgA density | concentration ((circle): control group average, (square): feed administration group, (triangle | delta): drinking water administration group) in the blood of a HIGA mouse | mouth. It is a figure which shows the serum albumin density | concentration ((circle): control group average, (square): feed administration group, (triangle | delta): drinking water administration group) of a HIGA mouse | mouth. It is a figure which shows the tissue IgA dyeing | staining image of the glomerular tissue of a HIGA mouse. It is a figure which shows the structure | tissue IgA dyeing | staining image of the intestinal epithelial tissue of a HIGA mouse.

Claims (6)

An aqueous extract of jackfruit seeds, which is a food additive for therapeutic and / or prophylactic use for patients with IgA nephropathy and mainly contains jacarin and / or jacarin derivatives. 2. The jackfruit seed water according to claim 1, wherein the jacarin and / or jacarin derivative is a jacalin complex having a jacarin molecular number of 1 to 10 and a molecular weight of 50 to 500 KDa. Extract. The water extract of jackfruit seed according to claim 1, wherein the jacarin and / or jacarin derivative is a hydrothermal decomposition product of a jacarin complex and has a molecular weight of 15 to 50 KDa. The water extract of jackfruit seed according to any one of claims 1 to 3, wherein the form of the water extract of jackfruit seed mainly comprising the jacarin and / or jacarin derivative is in a powder form. The water extract of the jackfruit seed according to any one of claims 1 to 3, wherein the form of the water extract of the jackfruit seed mainly composed of the jacarin and / or jacarin derivative is an aqueous solution. The aqueous extract of jackfruit seed according to any one of claims 1 to 5 is orally administered to an IgA nephropathy patient to remove IgA from the blood and / or tissue fluid of the patient. A method for preventing and / or treating IgA nephropathy.

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