Composition for internal use, and production method of the same

Abstract

To provide a composition for internal use which contains silica as a constituent, is composed of a safe material for an organism, and has excellent bioabsorbability, and a production method of the composition.SOLUTION: A composition for internal use of the present invention contains a composite of silica and peptide-derived compound as an active ingredient. The composition for internal use of the present invention can be produced by treating a mixture containing silica and peptide compound by enzyme. According to the composition for internal use of the present invention, silica absorbability into an organism can be increased, and the composition can be easily produced.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an internal composition and a method for producing the same, and more particularly to an internal composition with improved bioabsorbability and a method for producing the same. [Background technology]

[0002] Silica (SiO2) is found in human blood, hair, nails, bones, etc., and has been shown to affect bone formation, collagen formation, and immunity, and in recent years has been found to be involved in the prevention of osteoporosis. Silica must be ingested from external sources, and is manufactured and sold in the form of oral compositions such as supplements and beverages.

[0003] On the other hand, silica is generally divided into crystalline silica such as quartz and other amorphous silica, and the silica used in oral compositions is amorphous silica. It has been reported that such silica, when mixed with other materials such as collagen, exerts various effects on the body, including those mentioned above (for example, Patent Documents 1 and 2).

[0004] However, the efficiency of absorption of silica into the body is not necessarily sufficient, and further technological development to improve its absorbability into the body is desired. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Patent Publication No. 2021-029154 [Patent Document 2] Special Publication No. 2020-511399 Summary of the Invention [Problem to be solved by the invention]

[0006] The present invention aims to solve the above problems, and its object is to provide an internal composition containing silica as a constituent component, being made of materials that are safe for the body, and having good bioabsorbability, as well as a method for producing the same. [Means for solving the problem]

[0007] The present invention is an internal composition containing, as an active ingredient, a complex of silica and a peptide-derived compound.

[0008] In one embodiment, the peptide-derived compound is derived from animal peptides.

[0009] In one embodiment, the peptide-derived compound is derived from gelatin.

[0010] In one embodiment, the peptide-derived compound is derived from plant peptides.

[0011] In one embodiment, the peptide-derived compound is derived from soy protein.

[0012] In one embodiment, the complex is an enzyme-treated product of a mixture containing the silica and the peptide compound.

[0013] In one embodiment, the complex is one in which the peptide-derived compound is supported on the silica.

[0014] In one embodiment, the composite is collagen-supported silica.

[0015] The present invention also provides a method for producing an internal composition, which comprises treating a mixture of silica and a peptide compound with an enzyme.

[0016] In one embodiment, the mixing ratio of the silica to the peptide compound in the mixture is within the range of 1:0.3 to 1:2000 on a mass basis.

[0017] In one embodiment, the enzyme is a neutral protease.

[0018] In one embodiment, the peptide compounds are animal peptides.

[0019] In a further embodiment, the animal peptide is gelatin.

[0020] In one embodiment, the peptide compounds are plant peptides.

[0021] In a further embodiment, the plant peptides are soy proteins. [Effects of the Invention]

[0022] According to the present invention, it is possible to enhance the absorbability of silica in various living organisms such as humans, pet animals, livestock, poultry, farmed fish, etc. The internal composition of the present invention can be easily produced using materials that are safe for living organisms. [Brief explanation of the drawings]

[0023] [Figure 1] 1 is a graph showing the amount of inorganic silicon in blood samples obtained by feeding the internal compositions obtained in Examples 1 and 2 and Comparative Example 1 to rats. [Figure 2] 1 is a graph showing a wide-range photoelectron spectrum of the outermost surface of a sample using the oral composition (E2) obtained in Example 2. [Figure 3] 1 is a graph showing a wide-range photoelectron spectrum of the outermost surface of a sample prepared using the oral composition (C1) obtained in Comparative Example 1. [Figure 4] 1 is a graph showing narrow band photoelectron spectra of the outermost surface of each sample using the internal composition (E2) obtained in Example 2 and the internal composition (C1) obtained in Comparative Example 1. [Figure 5]1 is a graph showing a narrow band photoelectron spectrum in which the vertical axis intensity is normalized based on the broad band photoelectron spectrum obtained in Experimental Example 2. DETAILED DESCRIPTION OF THE INVENTION

[0024] The present invention will be described in detail below.

[0025] (Internal composition) The internal composition of the present invention contains a complex of silica and a peptide-derived compound as an active ingredient.

[0026] Here, the term "complex" in "complex of silica and peptide-derived compound" refers to a state in which the constituent components, silica and peptide-derived compound, are "complexed" by chemical bonding and / or physical adsorption, etc.; this does not include a simple mixture of silica and peptide-derived compound. For example, "collagen-supported silica" is included as one form of the above-mentioned "complex of silica and peptide-derived compound." Note that the term "supported" in collagen-supported silica refers to a "complex" of the constituent components, collagen and silica, by chemical bonding and / or physical adsorption, etc.; this does not include a simple mixture of collagen and silica. Therefore, collagen-supported silica can also be called a collagen-silica complex.

[0027] The silica in the present invention includes, for example, amorphous silica. Amorphous silica is generally composed of silicon dioxide that does not have regular molecular arrangement. Examples of amorphous silica include silica gel, precipitated silica, fumed silica, diatomaceous earth silica, and silica derived from rice husk, and combinations thereof. In the present invention, because it is intended for internal use such as oral administration, the silica is preferably amorphous silica used in supplements, beverages, etc., and more preferably silica preparations obtained from rice husk (silica derived from rice husk).

[0028] The amount of silica that can be contained in the rice husk-derived silica preparation is not necessarily limited, but preferably contains silica in a proportion of 40% to 99.9% by mass, more preferably 45% to 99% by mass, and even more preferably 46% to 98% by mass, relative to the total mass.

[0029] The amorphous silica can be classified into water-soluble and insoluble types depending on the manufacturing method. In the present invention, water-soluble amorphous silica is preferred in order to increase the absorption efficiency from the intestines of the living body.

[0030] The peptide-derived compounds of the present invention are degradation products of peptide compounds, for example, compounds generated by treating peptide compounds with the enzymes described below.

[0031] The term "peptide compound" as used herein is a general term for compounds formed by at least two amino acids, which may be the same or different, linked together via a peptide bond (-CO-NH-), and are also called peptides. Examples of peptide compounds of the present invention include dipeptides, tripeptides, tetrapeptides, oligopeptides, and polypeptides, as well as combinations thereof.

[0032] The peptide compounds may also be either animal peptides, plant peptides, or a combination thereof.

[0033] Animal peptides are obtained from parts of animals such as pigs, cows, and fish, and include animal-derived proteins. Specific examples of animal peptides include gelatin, collagen (peptide), milk protein (including whey protein and casein protein), chicken protein, salmon protein, cod protein, egg white protein, and combinations thereof.

[0034] For example, gelatin is extracted by applying heat to collagen contained in connective tissues such as skin, bones, and tendons of animals such as cows, pigs, and fish. Gelatin used as a peptide compound is preferably derived from fish because it has less of the odor characteristic of gelatin, has a low molecular weight, and is said to have good absorbability.

[0035] Plant peptides, also known as plant proteins, are obtained from parts of plants such as legumes (e.g., soybeans, adzuki beans, kidney beans, chickpeas, lentils, and fava beans), grains (e.g., brown rice, millet, oatmeal, quinoa, amaranth, and corn), nuts (e.g., almonds, walnuts, cashews, peanuts, pistachios, and macadamia nuts), and vegetables (e.g., broccoli, cauliflower, Brussels sprouts, avocado, spinach, and asparagus). Specific examples of plant peptides include soy protein, wheat protein, corn protein, rice (including brown rice) protein, pea protein, edamame protein, mung bean protein, fava bean protein, chickpea protein, pumpkin seed protein, wheat protein, almond protein, peanut protein, and potato protein, as well as combinations thereof.

[0036] On the other hand, the peptide-derived compounds of the present invention are those derived from the above-mentioned peptide compounds, and include, for example, those derived from animal peptides (e.g., degradation products of animal peptides), those derived from plant peptides (e.g., degradation products of plant peptides), and combinations thereof. For example, when collagen is used as a degradation product of gelatin (a peptide compound), it corresponds to the peptide-derived compound. Alternatively, when collagen itself is used as a peptide compound, its degradation product corresponds to the peptide-derived compound.

[0037] The complex of silica and a peptide-derived compound is preferably complexed with 0.3 to 1000 parts by mass, more preferably 2 to 20 parts by mass, and even more preferably 5 to 12 parts by mass of the peptide-derived compound per 1 part by mass of silica, which is the constituent component. If the amount of the peptide-derived compound constituting the complex is less than 0.3 parts by mass per 1 part by mass of silica, the resulting complex may have difficulty in exhibiting sufficient absorbability in the body. If the amount of the peptide-derived compound constituting the complex exceeds 1000 parts by mass per 1 part by mass of silica, a larger amount of complex must be ingested to absorb a given amount of silica into the body, and such ingestion itself may be difficult for the body.

[0038] The complex of the present invention is preferably obtained by enzymatically treating a mixture containing silica and a peptide compound as a raw material (enzyme-treated product). The enzymatically treated complex of silica and a peptide-derived compound can be produced, for example, by the method described below.

[0039] Furthermore, in the present invention, the complex of silica and a peptide-derived compound is, for example, collagen-supported silica, and is preferably in the form of a powder.

[0040] The internal composition of the present invention may contain other ingredients to the extent that they do not impair the effects of the complex of silica and the peptide-derived compound.

[0041] The other ingredients are, for example, additives that may be commonly used in the food and / or pharmaceutical fields. Specific examples of the other ingredients include excipients, lubricants, stabilizers, binders, disintegrants, flavors, sweeteners, and colorants, and combinations thereof.

[0042] Examples of excipients include xylitol, erythritol, sorbitol, lactose, sucrose, trehalose, crystalline cellulose, dextrin, starch, partially pregelatinized starch, sodium bicarbonate, anhydrous calcium phosphate, calcium hydrogen phosphate hydrate, tricalcium phosphate, calcium carbonate, precipitated calcium carbonate, calcium silicate, and calcium lactate, and combinations thereof.

[0043] Lubricants include, for example, stearic acid, calcium stearate, magnesium stearate, sodium stearyl fumarate, sucrose fatty acid esters, hydrogenated oils, glycerin, glycerin fatty acid esters, talc, and carnauba wax, and combinations thereof.

[0044] Examples of stabilizers include dextrin, α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, hydroxypropyl-β-cyclodextrin, hydroxypropyl cyclodextrin, sucrose fatty acid esters, and mannitol, and combinations thereof.

[0045] Examples of binders include pullulan, pectin, sodium alginate, gum arabic, guar gum, agar, starch syrup, hydroxypropyl cellulose, pregelatinized starch, polyvinylpyrrolidone, carboxyvinyl polymer, polyvinyl alcohol, ammonioalkyl methacrylate copolymer, ethyl cellulose, carboxyvinyl polymer, carboxymethyl ethyl cellulose, hypromellose, polyvinyl alcohol-polyethylene glycol graft copolymer, polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer, methyl cellulose, beeswax, macrogol, and methacrylic acid copolymer, and combinations thereof.

[0046] Disintegrants include, for example, carboxymethylcellulose, carmellose calcium, hydroxypropylcellulose, corn starch, partially pregelatinized starch, croscarmellose sodium, carboxymethyl starch sodium, and crospovidone, and combinations thereof.

[0047] Flavoring agents include, for example, vanilla, strawberry, orange, menthol, fennel oil, cinnamon oil, spruce oil, peppermint oil, and green tea powder, and combinations thereof.

[0048] Examples of sweetening agents include aspartame, stevia, saccharin, sucralose, acesulfame potassium, sorbitol, sucrose, reduced maltose syrup, and licorice, and combinations thereof.

[0049] Coloring agents include, for example, iron sesquioxide, yellow iron sesquioxide, black iron oxide, titanium oxide, talc, Food Yellow No. 4, Food Yellow No. 4 Aluminum Lake, Food Yellow No. 5, Food Red No. 2, Food Red No. 3, Food Red No. 102, Food Blue No. 1, methylene blue, carmine, and riboflavin, and combinations thereof.

[0050] The content of the other components in the internal composition of the present invention is not particularly limited, and an appropriate amount can be selected by a person skilled in the art based on, for example, the mass ratio of silica and the peptide-derived compound that constitute the complex used.

[0051] The internal composition of the present invention can be used as an oral preparation that can be ingested by animals such as humans, pets, livestock, poultry, and farmed fish, for example, as a food, drink, feed, or pharmaceutical product itself or as one of their constituent materials.

[0052] The internal composition of the present invention may also have any dosage form.Such dosage forms include, for example, powder, granules, pills, tablets, liquids, and capsules (for example, hard capsules and soft capsules).When the internal composition of the present invention is used as a food or drink, examples of such food or drink include general foods; supplements; health functional foods such as specified health foods, nutritional functional foods, and functional food; soft drinks; tea drinks; coffee drinks; processed milk; dairy drinks; soy milk; and alcoholic beverages.

[0053] (Method of manufacturing an internal composition) The internal composition of the present invention can be produced, for example, as follows.

[0054] In the production method of the present invention, first, a mixture of silica and a peptide compound is treated with an enzyme.

[0055] When obtaining a mixture of silica and a peptide compound, the mixing ratio is not necessarily limited, but is preferably 1:0.3 to 1:2000, more preferably 1:1 to 1:1000, even more preferably 1:2 to 1:20, and even more preferably 1:5 to 1:12. If the ratio of the peptide compound is less than 0.3 parts by mass per part by mass of silica, the resulting complex of silica and a peptide-derived compound may be difficult to absorb sufficiently into the body. If the ratio of the peptide compound is more than 1000 parts by mass per part by mass of silica, the resulting complex requires a larger intake to absorb a given amount of silica into the body, which may make the intake itself difficult.

[0056] The mixture of silica and peptide compound is preferably heated, with water added as needed, until the peptide compound is completely dissolved before enzymatic treatment. The water that can be added to the mixture is not particularly limited, and may be, for example, distilled water, ion-exchanged water, RO water, or tap water. The heating temperature of the mixture is not particularly limited, but is preferably 60°C to 98°C, more preferably 65°C to 90°C. The mixture may be stirred by any means known in the art until the peptide compound is completely dissolved.

[0057] The enzyme used to treat the mixture is preferably a protease, more preferably a neutral protease. Proteases are enzymes capable of hydrolyzing peptide bonds in the substrate (gelatin), such as peptidases and proteinases, and combinations thereof.

[0058] The protease is preferably derived from a microorganism because it is versatile and can be used with a wide range of animal peptides. Examples of microorganisms that produce proteases include microorganisms from the genus Bacillus (e.g., Bacillus subtilis) and microorganisms from the genus Aspergillus (e.g., Aspergillus oryzae). In the present invention, one or more types of proteases may be used in combination.

[0059] The amount of protease that can be used can be appropriately selected by those skilled in the art based on, for example, 100 g of the peptide compound to be treated. By appropriately selecting the amount of protease used, a complex of silica and a peptide-derived compound can be efficiently obtained.

[0060] The enzyme treatment of the mixture is preferably carried out under heating. The heating temperature of the mixture for the enzyme treatment is not necessarily limited, but a temperature of 45°C to 65°C, more preferably 50°C to 60°C, is selected so that the enzyme used can act most efficiently. The treatment time is not particularly limited because it varies depending on the amount of silica and / or peptide compound used, the mass ratio thereof, etc., and an appropriate time can be selected by those skilled in the art.

[0061] The enzyme is then inactivated using techniques known to those skilled in the art.

[0062] The resulting enzyme-treated product may then be filtered as needed, and processed into a powder form by, for example, spray drying or drying and pulverization using means known to those skilled in the art.

[0063] In this way, a complex of silica and a peptide-derived compound can be obtained.

[0064] The complex obtained as described above may be mixed with the other ingredients as needed, and may further be processed into an appropriate dosage form as needed using means known to those skilled in the art.

[0065] In this way, the oral composition of the present invention can be produced. [Example]

[0066] The present invention will be described in detail below with reference to examples, although the present invention is not limited to these examples.

[0067] (Example 1: Preparation of an internal composition (E1) using gelatin) A silica preparation derived from rice husks and gelatin derived from fish skin were mixed to contain 100 parts by mass of silica and 100 parts by mass of gelatin, and approximately 10 times the amount of tap water was added to this.The mixture was stirred while maintaining the temperature at 70°C to 80°C until the gelatin was completely dissolved, obtaining a mixture.

[0068] To this mixture, a neutral protease preparation (containing a neutral protease derived from Bacillus subtilis) was added in a ratio of 0.5 parts by mass relative to the amount of gelatin, and another neutral protease preparation (containing a neutral protease derived from Aspergillus oryzae) was added in a ratio of 1 part by mass relative to the amount of gelatin, and the mixture was treated at 55°C for 240 minutes. The enzyme-treated product was then heated at 90°C for 60 minutes to inactivate the enzyme, and then allowed to stand overnight.

[0069] The mixture was then filtered, and the filtrate was spray-dried to obtain powdered collagen-supported silica (silica to collagen composition ratio 1:1 by mass), which was used as an internal composition (E1) as is.

[0070] (Example 2: Preparation of an internal composition (E2) using gelatin) Powdered collagen-supported silica was obtained in the same manner as in Example 1, except that 500 parts by mass of gelatin (fish-derived gelatin; Gelatin AF-250 manufactured by Jellice Co., Ltd.) was used. This was used as an internal composition (E2) as is.

[0071] (Comparative Example 1: Preparation of Internal Composition (C1) Using Gelatin) A neutral protease preparation (containing a neutral protease derived from Bacillus subtilis) was added to 500 parts by mass of gelatin (fish-derived gelatin) at a ratio of 0.5 parts by mass relative to the amount of gelatin, and another neutral protease preparation (containing a neutral protease derived from Aspergillus oryzae) was added at a ratio of 1 part by mass relative to the amount of gelatin, and the mixture was treated at 55°C for 240 minutes. The enzyme was then inactivated by heating at 90°C for 60 minutes, and the mixture was allowed to stand overnight to obtain an enzyme-treated product composed of collagen.

[0072] Thereafter, 500 parts by mass of silica in the form of a silica preparation derived from rice husks was simply mixed with the enzyme-treated product to obtain an internal composition (C1).

[0073] (Experimental Example 1: Bioabsorption of silica from an internal composition using rats) Six-week-old rats (Crl:CD(SD)[SPF]; Jackson Laboratory Japan; 14 males) were purchased and, after a quarantine and acclimation period, were randomly assigned to three groups of four rats each based on body weight. Rats excluded from group assignment were used for time-0 (non-administration) sample collection.

[0074] On the other hand, a small amount of water was added to 4116 mg of the internal composition (E1) obtained in Example 1, and the mixture was mixed using a vortex mixer to disperse uniformly. Further water was added to bring the total volume to 20 mL, thereby obtaining an administration liquid (EA1) dispersion of the internal composition (E1).

[0075] In addition, a small amount of water was added to 1200 mg of the internal composition (E2) obtained in Example 2, and the mixture was mixed and dispersed uniformly using a vortex mixer. Further water was added to bring the total volume to 20 mL, thereby obtaining an administration solution (EA2) of the internal composition (E2).

[0076] Furthermore, a small amount of water was added to 4067 mg of the oral composition (C1) obtained in Comparative Example 1, and the mixture was mixed and dispersed uniformly using a vortex mixer. Further water was added to bring the total volume to 20 mL, thereby obtaining an administration solution (CA1) of the oral composition (C1).

[0077] From the evening of the day before the experiment, all animals, including those excluded from the group, were fasted (for 16 hours or more) until the end of the experiment. However, they were not deprived of water.

[0078] The administration solutions (EA1), (EA2) and (CA1) prepared above were filled into a syringe equipped with an oral probe while stirring, and administered orally to rats in each group at the doses shown in Table 1.

[0079] [Table 1]

[0080] After the start of administration, blood samples were collected 0.5 hours, 1 hour, and 2.5 hours later as follows.

[0081] First, approximately 1.2 mL of blood was collected from the jugular vein of animals anesthetized with isoflurane at 0.5 and 1 hour after the start of administration. 2.5 hours after the start of administration, rats underwent laparotomy under isoflurane anesthesia, and whole blood was collected from the posterior vena cava. For rats excluded from the group, rats underwent laparotomy under isoflurane anesthesia and whole blood was collected from the posterior vena cava to serve as a time point 0 sample.

[0082] The collected blood was placed in a blood collection tube (Venoject II) containing a coagulation-promoting film and separating agent, and the resulting blood was centrifuged at 1700 x g for 7 minutes at room temperature to separate the serum. The resulting serum (0.5 mL or more at each point) was stored in a deep freezer, and the blood silicon concentration was measured (inorganic silicon, ICP-OES2 method).

[0083] The mean and standard error of the obtained blood silicon concentration (inorganic silicon) were calculated for each group at each blood sampling time point. Furthermore, for comparisons between groups, a test for homogeneity of variance was performed using the Bartlett method, and in the case of homogeneity of variance, mean values ​​were compared using the Tukey method. In the case of unequal variance, mean ranks were compared using the Steel-Dwass method. The significance level for the Bartlett method was set at a risk level of 5%, and for the Tukey and Steel-Dwass methods, the significance levels were set at a risk level of 5% and 1%. The results are shown in Figure 1.

[0084] As shown in Figure 1, the bioabsorbability in rats of both the oral compositions (E1) (administration solution (EA1)) and (E2) (administration solution (EA2)) obtained in Examples 1 and 2 was improved compared to that of the oral composition (C1) (administration solution (CA1)) obtained in Comparative Example 1, which was a simple mixture.

[0085] (Experimental Example 2: XPS analysis of internal composition using rats) The internal composition (E2) obtained in Example 2 and the internal composition (C1) obtained in Comparative Example 1 were each pressed against an In plate and held in place, and each was subjected to XPS analysis using a scanning X-ray photoelectron spectrometer (PHI5000 VersaProbe III manufactured by Alpac-Phi) under the measurement conditions shown in Table 2 below.

[0086] [Table 2]

[0087] Specifically, after obtaining a broad-band photoelectron spectrum through XPS analysis, narrow-band photoelectron spectra for the elements of interest (C, N, O, and Si) were obtained, and the elemental composition ratio was calculated from the area intensity and relative sensitivity coefficient of the obtained photoelectron peaks.The chemical bonding state of Si between samples was compared, and it was investigated whether silica was bound to peptided proteins (collagen).

[0088] The broad-range photoelectron spectrum of the outermost surface of the sample using the internal composition (E2) obtained in Example 2 is shown in Figure 2, and the broad-range photoelectron spectrum of the outermost surface of the sample using the internal composition (C1) obtained in Comparative Example 1 is shown in Figure 3. The narrow-range photoelectron spectra of the outermost surfaces of these samples are shown in Figure 4. Furthermore, the elemental composition ratios of the outermost surfaces of the samples obtained in this manner are shown in Table 3, and the narrow-range photoelectron spectra with normalized vertical axis intensity are shown in Figure 5.

[0089] [Table 3]

[0090] As shown in Table 3, the internal composition (E2) of Example 2 was primarily composed of carbon (C), whereas the internal composition (C1) of Comparative Example 1 was primarily composed of carbon and oxygen (C). Focusing on the carbon (C) value, the value (61.5 at%) of the internal composition (E2) of Example 2 was nearly twice the value (31.9 at%) of the internal composition (C1) of Comparative Example 1. This suggests an increase in carbon bonds, i.e., an increase in carbon bonds in the internal composition (E2) of Example 2. Focusing on the silicon (Si) value, the value (0.7 at%) of the internal composition (E2) of Example 2 was lower than the value (14.9 at%) of the internal composition (C1) of Comparative Example 1. This suggests that the collagen combined with silica to cover the silicon, preventing its detection. Even considering this, it can be inferred that a chemical bond was formed between the collagen and silica.

[0091] Furthermore, according to Figure 5, the peak position of Si differs between samples, and the peak position of the internal composition (E2) of Example 2 is on the lower binding energy side compared to silica (SiO2) of the internal composition (C1) of Comparative Example 1, so it can be assumed that it has a Si-O bond different from SiO2.

[0092] From this, it can be inferred that the collagen-supported silica constituting the internal composition (E2) of Example 2 is a complex having a Si-O bond different from SiO2, compared to that of the internal composition (C1) of Comparative Example 1, which is a simple mixture.

[0093] Example 3: Preparation of an internal composition (E3) using soy protein 100 parts by mass of a silica preparation derived from rice husks and 500 parts by mass of soy protein (Showa Fresh M-600 manufactured by Showa Sangyo Co., Ltd.) were mixed, and about 6 times the amount of tap water was added thereto and stirred to obtain a mixture.

[0094] To this mixture, a protease preparation (containing a papaya-derived protease) was added in a ratio of 0.6 parts by mass relative to the amount of soy protein, and another peptidase preparation (containing a Rhizopus-derived peptidase) was further added in a ratio of 0.03 parts by mass relative to the amount of soy protein, and the mixture was treated at 50-55°C for 120 minutes. The enzyme-treated product was then heated at 95°C for 30 minutes to inactivate the enzyme, and allowed to stand overnight.

[0095] The mixture was then filtered, and the filtrate was spray-dried to obtain a powder of soy protein-supported silica, which was designated as an internal composition (E3).

[0096] (Comparative Example 2: Preparation of an internal composition (C2) using soy protein) A protease preparation (containing a papaya-derived protease) was added to 500 parts by mass of soy protein in a ratio of 0.6 parts by mass relative to the amount of the protein, and another peptidase preparation (containing a Rhizopus-derived peptidase) was added in a ratio of 0.03 parts by mass relative to the amount of the protein, and the mixture was treated at 50-55°C for 120 minutes. The enzyme was then inactivated by heating at 95°C for 30 minutes, and the mixture was allowed to stand overnight to obtain an enzyme-treated product composed of soy protein.

[0097] Thereafter, 100 parts by mass of silica was simply mixed with the enzyme-treated product to obtain an internal composition (C2).

[0098] Comparative Example 3: Preparation of Oral Composition (C3) (Control) As a control for silica alone, a silica preparation derived from rice husk was used as an internal composition (C3) and was used in the following experiments.

[0099] (Experimental Example 1: Bioabsorption of silica from an internal composition using rats) Six-week-old rats (Japan SLC Co., Ltd.; 14 males) were purchased and, after a quarantine and acclimation period, were randomly assigned to three groups of four rats each based on body weight. Rats excluded from group assignment were used to collect samples at time 0 (unadministered).

[0100] A small amount of water is added to 11612 mg of the internal composition (E3) obtained in Example 3, and the mixture is mixed and dispersed uniformly using a vortex mixer. Further water is added to bring the total volume to 40 mL to obtain an administration solution (EA3) of the internal composition (E3).

[0101] In addition, a small amount of water is added to 11,848 mg of the internal composition (C2) obtained in Comparative Example 2, and the mixture is mixed and dispersed uniformly using a vortex mixer. Further water is added to bring the total volume to 40 mL to obtain an administration solution (CA2) of the internal composition (C2).

[0102] Furthermore, a small amount of water is added to 1904 mg of the oral composition (C3) of Comparative Example 3, and the mixture is mixed and dispersed uniformly using a vortex mixer. Further water is added to bring the total volume to 40 mL to obtain an administration solution (CA3) of the oral composition (C3).

[0103] Starting in the evening of the day before the experiment, all animals, including those excluded from the group, are fasted (for at least 16 hours). Water is not withheld. Fasting continues until the end of the experiment.

[0104] For each group of rats, fill a syringe equipped with an oral probe with the above-prepared administration solutions (EA3), (CA2), and (CA3) while stirring, and administer a single oral dose to each animal by force. The volume of the administration solution is calculated at a rate of 20 mL / kg using the body weight before administration, and is rounded to one decimal place.

[0105] Blood samples were collected 1 hour, 1.5 hours, and 2 hours after the start of administration as follows: Approximately 1 mL of blood was collected from the jugular vein of each animal. The blood was placed in an Eppendorf tube and centrifuged at 4000 rpm for 15 minutes at 4°C to separate the plasma. The plasma (0.5 mL or more at each time point) was stored in a deep freezer (-80°C) and the blood silicon concentration was measured (inorganic silicon, ICP-MS method).

[0106] Calculate the mean and standard error. Test for equality of variances using the Bartlett method. If the variances are equal, compare the mean values ​​using Student's t-test. If the variances are unequal, compare the mean ranks using the Wilcoxon rank sum test. For the Bartlett method, the significance level is set at 5%, and for the Student's t-test and Wilcoxon rank sum test, the significance levels are set at 5% and 1%.

[0107] As a result, it was confirmed that the bioabsorbability in rats of the oral composition (E3) (administration solution (EA3)) obtained in Example 3 was improved compared to that of the oral compositions (C2) and (C3) (administration solutions (CA2) and (CA3)) of Comparative Examples 2 and 3. [Industrial Applicability]

[0108] The present invention is useful in technical fields such as the food field and the pharmaceutical field.

Claims

1. An internal composition containing a complex of silica and a peptide-derived compound as an active ingredient.

2. The oral composition according to claim 1, wherein the complex is an enzyme-treated mixture containing the silica and the peptide compound.

3. The internal composition according to claim 1, wherein the complex is a compound derived from a peptide supported on silica.

4. The oral composition according to claim 1, wherein the complex is collagen-supported silica.

5. A method for producing an internal composition, comprising treating a mixture of silica and a peptide compound with an enzyme.

6. The method according to claim 5, wherein the mixture has a ratio of silica to peptide compound in the range of 1:0.3 to 1:2000 by mass.

7. The method of claim 5 , wherein the enzyme is a neutral protease.

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