WO2013051572A1 - 感覚改善剤 - Google Patents
感覚改善剤 Download PDFInfo
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- WO2013051572A1 WO2013051572A1 PCT/JP2012/075544 JP2012075544W WO2013051572A1 WO 2013051572 A1 WO2013051572 A1 WO 2013051572A1 JP 2012075544 W JP2012075544 W JP 2012075544W WO 2013051572 A1 WO2013051572 A1 WO 2013051572A1
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- milk
- derived protein
- product
- sensation
- improving
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Definitions
- the present invention includes a sensory improver having the effect of improving peripheral nerve dullness, comprising the following milk-derived protein and / or a degradation product of milk-derived protein as an active ingredient, and a sensory-improvement food and drink containing this sensory improver.
- a sensory improver having the effect of improving peripheral nerve dullness, comprising the following milk-derived protein and / or a degradation product of milk-derived protein as an active ingredient, and a sensory-improvement food and drink containing this sensory improver.
- peripheral sensation is caused not only by aging but also by diseases such as diabetes.
- Sensation of peripheral sensation causes problems such as being unable to feel correctly hot when touching a hot object, increasing the risk of burns, etc., and delaying the detection of injury due to dullness of pain.
- sphingomyelinase and phosphatidylcholine-specific phospholipase C which are effective in increasing the biosynthesis of exogenous ceramide and endogenous ceramide, are mediated through 3T3 cells, which are established fibroblasts.
- Non-patent Document 1 It has been reported that neurotrophic factors secreted from cells promote morphological differentiation of P-12 cells, which are neural model cells. The promotion of morphological differentiation of neural model cells suggests an effect of improving peripheral sensory dullness.
- ceramides and enzymes are not food ingredients, it is necessary to consider safety when using them. Under such circumstances, there is a demand for an agent that is safer and effective in improving the slowing of sensation in the periphery by daily ingestion or application to the skin.
- milk-derived sphingomyelin and phospholipids have an effect to improve this against the slowing of peripheral sensation.
- Patent Document 1 and Patent Document 2 there is no known effect on milk-derived proteins on peripheral sensation.
- milk-derived proteins include lactoperoxidase, lactoferrin, cystatin, and angiogenin.
- Lactoperoxidase is a glycoprotein present in milk and containing heme iron, but its detailed structure has not yet been clarified. Regarding the use of lactoperoxidase, we found that it has an inhibitory effect on the formation of lipid peroxides in vivo, and it is used as an anti-aging agent to prevent vision loss, motor ability decline, immune function decline, etc. In addition, since it has a low palpation effect, its use as a low palpation nutrition composition is known. However, it is not known that lactoperoxidase and an enzyme degradation product obtained by decomposing it with a proteolytic enzyme have an action of improving blunting of peripheral nerves and are useful as a sensory improvement agent.
- Lactoferrin and its degradation products are known to have an effect of preventing the adhesion of pathogenic bacteria to cells and an antiviral effect. Further, it has been reported that mixing with epidermal growth factor enhances the skin cell activation effect of epidermal growth factor alone. In general, lactoferrin is known to have an action of reducing stress associated with pain and mental stress. However, it is not known that an enzyme degradation product obtained by degradation with lactoferrin and its proteolytic enzyme has an action of improving the peripheral nerve blunting and is useful as a sensory improvement agent.
- Cystatin as a cysteine protease inhibitor, is a substance that inhibits the proteolytic activity of cysteine protease having an SH group at the active center, and is found in animal tissues, cells, blood and urine.
- cystatin a virus growth inhibitory action has been confirmed.
- an enzyme degradation product obtained by degrading with cystatin and its proteolytic enzyme has an action of improving peripheral nerve blunting and is useful as a sensory improvement agent.
- Angiogenin is one of the angiogenic factors.
- Human angiogenin is known to be a protein having a molecular weight of 14,400, and is present in blood and milk.
- Usian diogenin the determination of the amino acid sequence has already been reported by isolating angiogenin in milk.
- the milk is adsorbed on cation exchange chromatography and then eluted with an aqueous alkali metal salt solution of a weak organic acid.
- the eluate is again subjected to cation exchange chromatography and gel filtration chromatography. The method of recovering is disclosed.
- angiogenin specifically suppresses melanin production in B-16 cells, which are melanoma cells, it is also reported that it can be used as a whitening agent.
- an enzyme degradation product obtained by degrading with angiogenin and its proteolytic enzyme has an action to improve blunting of peripheral nerves and is useful as a sensory improvement agent.
- An object of the present invention is to provide a sensation-improving agent that is safe and exhibits the effect of improving the dullness of sensation in the periphery by daily ingestion or application to the skin. Moreover, this invention makes it a subject to provide the food / beverage products for sensation improvement or feed, and cosmetics which show the effect which improves the blunting of the sensation in the periphery by oral ingestion or application
- the present inventors have conducted earnest searches for ingredients that are safe and have an excellent improvement effect on the slowing of sensation.
- any of milk-derived protein and / or milk-derived protein degradation product has been developed. It has been found that the sensation, particularly the peripheral sensation, can be improved by ingesting or applying it directly to the skin.
- the use of these as active ingredients has led to the completion of a sensory improvement agent.
- this sensory improvement agent can be mix
- lactoperoxidase lactoferrin
- cystatin cystatin
- angiogenin milk-derived proteins
- milk-derived proteins with the characteristic that they are contained in milk, but these proteins used in the sensory improvement agent of the present invention are not necessarily It may not be derived from milk, and may be artificially synthesized or purified from blood or the like.
- the present invention (1) A sensory improvement agent comprising milk-derived protein and / or milk-derived protein degradation product as an active ingredient.
- the proteolytic enzyme is at least one selected from the group consisting of pepsin, trypsin, chymotrypsin, and pancreatin.
- a food or drink for improving sensation, a feed, or a cosmetic comprising the component according to any one of (1) to (4).
- (6) A method for improving a mammal's sensation by allowing a mammal to ingest or apply milk-derived protein and / or milk-derived protein degradation product to the skin.
- (7) The method according to (6), wherein the mammal is a human, and 10 mg or more of milk-derived protein and / or milk-derived protein degradation product is ingested per adult per day.
- the sensation-improving agent of the present invention can provide an effect of improving peripheral sensation.
- milk-derived protein and / or milk-derived protein degradation product is used as an active ingredient.
- milk-derived proteins include lactoperoxidase, lactoferrin, cystatin, and angiogenin, and those obtained from milk from mammals such as humans, cows, buffalos, goats and sheep, and those produced by genetic engineering techniques are used. Is possible.
- the milk-derived protein degradation product can be obtained by allowing a protease to act on these milk-derived proteins.
- Lactoperoxidase is prepared from mammalian milk. Examples of the source include milk such as humans, cows, buffalos, goats and sheep. Lactoperoxidase is a known substance and is commercially available. To produce it, a known method, for example, a method for purifying lactoperoxidase using a sulfonated carrier (Japanese Patent Laid-Open No. Hei 3). -109400) can be used industrially. In the present invention, lactoperoxidase produced by genetic engineering techniques can also be used.
- the lactoperoxidase degradation product is a limited degradation of the above-mentioned lactoperoxidase with a proteolytic enzyme such as trypsin, pancreatin, chymotrypsin, pepsin, papain, kallikrein, cathepsin, thermolysin, and V8 protease so that the molecular weight is 10,000 or less.
- a proteolytic enzyme such as trypsin, pancreatin, chymotrypsin, pepsin, papain, kallikrein, cathepsin, thermolysin, and V8 protease so that the molecular weight is 10,000 or less.
- Peptide mixture The molecular weight lower limit is preferably 500 or more.
- Lactoferrin is prepared from mammalian milk. Examples of the source include milk such as humans, cows, buffalos, goats and sheep. Lactoferrin is a known substance and is commercially available. To produce it, a known method, for example, a method of purifying lactoferrin using a sulfonated carrier (JP-A-3-109400). ) Can be used industrially. In the present invention, lactoferrin produced by genetic engineering techniques can also be used.
- a lactoferrin degradation product is a peptide mixture obtained by limiting degradation of the above lactoferrin with a proteolytic enzyme such as trypsin, pancreatin, chymotrypsin, pepsin, papain, kallikrein, cathepsin, thermolysin, V8 protease, etc. so that the molecular weight is 10,000 or less. is there.
- the lower limit of the molecular weight is preferably 500 or more.
- Cystatin be of any origin, such including human, bovine, buffalo, goat, those derived from milk sheep like can also be used.
- human and bovine cystatins have already been clarified in gene sequences and can be produced by gene recombination.
- cystatins produced by genetic engineering techniques can also be used. Cystatin is contained in a relatively large amount in bovine colostrum and may be recovered from milk. Further, cystatin can be recovered from the culture medium of cell culture, and even those derived from such cells can be used.
- cystatin derived from milk can be produced according to a known method (Japanese Patent Laid-Open No. 2000-28187).
- Cystatin can be obtained by performing various chromatographic treatments such as ion exchange chromatography and gel filtration chromatography, ultrafiltration treatment and the like.
- cystatin degradation product a peptide mixture obtained by limiting degradation of cystatin with a proteolytic enzyme such as trypsin, pancreatin, chymotrypsin, pepsin, papain, kallikrein, cathepsin, thermolysin, V8 protease and the like to have a molecular weight of 8,000 or less is used. It is possible. However, the lower limit of the molecular weight is preferably 500 or more.
- angiogenin As a source of angiogenin, humans, cows, buffaloes, goats, sheep, etc. are suitable because they have high angiogenin content in colostrum within 1 to 7 days after delivery, particularly preferably within 1 to 5 days after delivery. Even normal lactating milk can be used as the raw material of the present invention.
- a known method for example, a method of purifying angiogenin by combining cation exchange chromatography and gel filtration chromatography (JP-A-2-296000, etc.) can be used industrially. it can.
- An angiogenin degradation product is a peptide obtained by limiting and degrading the above angiogenin with a proteolytic enzyme such as trypsin, pancreatin, chymotrypsin, pepsin, papain, kallikrein, cathepsin, thermolysin, and V8 protease so that the molecular weight is 10,000 or less. It is a mixture.
- the lower limit of the molecular weight is preferably 500 or more.
- the sensation improving agent of the present invention is a sensation improving agent as it is obtained by reacting the milk-derived protein, particularly lactoperoxidase, lactoferrin, cystatin, angiogenin, or milk-derived protein with a proteolytic enzyme. It can also be used, but in addition to this, it can be mixed with sugars, lipids, proteins, vitamins, minerals, flavors, other pharmaceuticals, raw materials usually used in foods, drinks and feeds, etc. It can also be formulated into powders, granules, tablets, capsules, drinks and the like. Moreover, as a coating agent, it can be used with normal application forms, such as emulsion, cream, lotion, and a pack.
- these coating agents are produced by a conventional method, and the milk-derived protein and / or milk-derived protein degradation product, which is the active ingredient of the present invention, may be appropriately blended during the production process, and can also be used as cosmetics. Further, in addition to milk-derived protein and / or milk-derived protein degradation product, other components showing sensory improvement effects such as ceramide, sphingomyelinase, sphingomyelin and the like can be used together. As an effective amount of the sensory improvement agent of the present invention, 10 mg or more, preferably 20 mg or more of milk-derived protein and / or milk-derived protein degradation product per 1 kg of body weight is orally administered in the mouse test described below.
- the amount is 0.001 to 40% by weight, more preferably 0.1 to 10% by weight, based on the total amount of the skin coating agent.
- milk-derived protein and / or milk-derived protein degradation product may be blended with ordinary food and drink such as yogurt, milk drink, wafer, dessert and the like.
- ordinary food and drink such as yogurt, milk drink, wafer, dessert and the like.
- milk-derived protein per 100 g of food or drink And / or 0.5 to 2000 mg of milk-derived proteolysate is preferably blended.
- the feed for sensory improvement of this invention should just mix
- milk-derived protein and / or milk-derived protein degradation product for these feeds, in order to ingest 10 mg or more of milk-derived protein and / or milk-derived protein degradation product, milk-derived protein and / or 100 g of feed Alternatively, it is preferable to mix 0.5 to 2000 mg of milk-derived protein degradation product.
- the method for blending milk-derived protein and / or milk-derived protein degradation product is not particularly limited.
- milk-derived protein and / or milk-derived protein degradation product is added. After suspending or dissolving in deionized water and stirring and mixing, it is prepared and used in the form of pharmaceuticals, foods and drinks, and feeds.
- milk-derived proteins and / or milk-derived protein degradation products may be mixed uniformly, and stirring and mixing may be performed using an ultradisperser, a TK homomixer, or the like.
- the solution of the said composition can be used by concentrating with an RO membrane etc.
- the sterilization process normally used for manufacture of a pharmaceutical, food-drinks, and feed can be performed, and if it is a powder form, dry heat sterilization is also possible. Therefore, various forms of pharmaceuticals, foods and drinks, and feeds such as liquids, gels, powders, and granules containing the milk-derived protein and / or milk-derived protein degradation product of the present invention can be produced.
- a column (diameter 5 cm ⁇ height 30 cm) packed with 400 g of a cation exchange resin sulfonated chitopearl (Fuji Boseki Co., Ltd.) was thoroughly washed with deionized water, and then 40 L of unsterilized skim milk (pH 6. 7) was passed at a flow rate of 25 ml / min. After passing, the column was thoroughly washed with deionized water and eluted with 0.02 M carbonate buffer (pH 7.0) containing 2.0 M sodium chloride.
- the elution fraction containing lactoperoxidase was adsorbed on an S-Sepharose FF column (manufactured by GE Healthcare), washed thoroughly with deionized water, and equilibrated with 10 mM phosphate buffer (pH 7.0). The fraction adsorbed with a linear gradient of 0 to 2.0 M sodium chloride was eluted, and the fraction containing lactoperoxidase was recovered. And the fraction was processed by gel filtration chromatography using HiLoad16 / 60 Superdexd75 pg (manufactured by GE Healthcare) to obtain 3.0 g of lactoperoxidase. In addition, the purity of the lactoperoxidase thus obtained is 94% and can be used as it is as a sensory improvement agent (Example product 1).
- Example 1 1 g of lactoperoxidase obtained in Example 1 was dissolved in 200 ml of water, and pancreatin (manufactured by Sigma) as a proteolytic enzyme was added so that the final concentration was 0.01% by weight, and the enzyme was incubated at 37 ° C. for 5 hours. Processed. And after heat-processing at 90 degreeC for 5 minute (s) and deactivating an enzyme, it freeze-dried and 0.8g of lactoperoxidase degradation products were obtained. In addition, the molecular weight of the lactoperoxidase degradation product thus obtained is 10,000 or less, and can be used as it is as a sensation improving agent (Example product 2).
- lactoperoxidase degradation product 1 g of lactoperoxidase obtained in Example 1 was dissolved in 200 ml of water, and trypsin (manufactured by Sigma) as a proteolytic enzyme was added to a final concentration of 0.01% by weight, followed by enzyme treatment at 37 ° C. for 5 hours. did. And after heat-processing at 90 degreeC for 5 minute (s) and deactivating an enzyme, it freeze-dried and 0.9g of lactoperoxidase degradation products were obtained. In addition, the molecular weight of the lactoperoxidase degradation product thus obtained is 10,000 or less, and can be used as it is as a sensory improvement agent (Example product 3).
- a column (diameter 5 cm ⁇ height 30 cm) packed with 400 g of a cation exchange resin sulfonated chitopearl (Fuji Boseki Co., Ltd.) was thoroughly washed with deionized water, and then 40 L of unsterilized skim milk (pH 6. 7) was passed at a flow rate of 25 ml / min. After passing through the column, the column was thoroughly washed with deionized water and eluted with 0.02 M sodium carbonate buffer (pH 7.0) containing 2.0 M sodium chloride.
- a cation exchange resin sulfonated chitopearl Fruji Boseki Co., Ltd.
- the eluted fraction containing lactoferrin is adsorbed on an S-Sepharose FF column (manufactured by GE Healthcare), washed thoroughly with deionized water, equilibrated with 10 mM phosphoric acid buffer (pH 7.0), and then 0.
- the adsorbed fraction was eluted with a linear gradient of ⁇ 2.0 M sodium chloride, and the fraction containing lactoferrin was collected. Then, the fraction was subjected to gel filtration chromatography using HiLoad 16/60 Superdex 75 pg (manufactured by GE Healthcare) to obtain 8.0 g of lactoferrin.
- the purity of the lactoferrin obtained in this way is 96% and can be used as it is as a sensation improving agent (Example product 4).
- Example 4 1 g of lactoferrin obtained in Example 4 was dissolved in 200 ml of water, and pancreatin (manufactured by Sigma) as a proteolytic enzyme was added so that the final concentration was 0.01% by weight. Enzyme treatment was performed at 7 ° C. for 5 hours. And after heat-processing at 90 degreeC for 5 minute (s) and deactivating an enzyme, it freeze-dried and 0.8 g of lactoferrin degradation products were obtained. In addition, the molecular weight of the lactoferrin degradation product obtained in this way is 10,000 or less, and can be used as it is as a sensation improving agent (Example Product 5).
- lactoferrin degradation product obtained in Example 4 1 g was suspended in 200 ml of water, and trypsin (manufactured by Sigma) as a proteolytic enzyme was added to a final concentration of 0.01% by weight, followed by enzyme treatment at 37 ° C. for 5 hours. And after heat-processing at 90 degreeC for 5 minute (s) and deactivating an enzyme, it freeze-dried and 0.9g of lactoferrin degradation products were obtained.
- the molecular weight of the lactoferrin degradation product obtained in this way is 10,000 or less, and can be used as it is as a sensory improvement agent (Example product 6).
- the column packed with 3,000 g of S Sepharose was thoroughly washed with deionized water, passed through 10,000 L of skim milk, washed thoroughly with deionized water, and then a linear concentration of 0.1 to 1.0 M sodium chloride. Elute with a gradient.
- the obtained fraction was heat-treated at 90 ° C. for 10 minutes and centrifuged to remove the precipitate. And the elution fraction containing a milk origin basic cystatin was fractionated again by MonoS ion exchange chromatography.
- this fraction was subjected to MonoQ ion exchange chromatography and Superose12 gel filtration chromatography using an FPLC system, and further processed sequentially with hydroxyapatite chromatography and C4 reverse phase chromatography using an HPLC system to obtain cystatin 58 mg (fraction A). Got.
- the cystatin thus obtained can be used as it is as a sensory improvement agent (Example product 7).
- the eluted fraction was immediately neutralized with 1M sodium hydroxide solution, fractionated by MonoS anion exchange chromatography, followed by sequential treatment with hydroxyapatite chromatography and C4 reverse phase chromatography on an HPLC system, and the milk-derived basicity 48 mg of cystatin (fraction B) was obtained.
- the cystatin thus obtained can be used as it is as a sensory improvement agent (Example product 8).
- Example 7 Fraction A 25 mg obtained in Example 7 was suspended in 100 ml of water, pancreatin was added to a final concentration of 1%, and enzyme treatment was performed at 37 ° C. for 5 hours. Then, the enzyme was inactivated by heat treatment at 90 ° C. for 5 minutes, and then lyophilized to obtain 23 mg of cystatin degradation product (fraction C). In addition, 25 mg of fraction B obtained in Example 8 was treated in the same manner to obtain 24 mg of cystatin degradation product (fraction D). The molecular weight of the cystatin degradation product thus obtained is 8,000 or less, and can be used as it is as a sensory improvement agent (Example product 9).
- a column (diameter 5 cm ⁇ height 30 cm) packed with 400 g of a cation exchange resin sulfonated chitopearl (Fuji Boseki Co., Ltd.) was thoroughly washed with deionized water, and then 40 L of unsterilized skim milk (pH 6. 7) was passed at a flow rate of 25 ml / min. After passing through the column, the column was thoroughly washed with deionized water and eluted with 0.02 M sodium carbonate buffer (pH 7.0) containing 2.0 M sodium chloride.
- a cation exchange resin sulfonated chitopearl Fruji Boseki Co., Ltd.
- the elution fraction containing angiogenin was adsorbed on an S-Sepharose FF column (manufactured by GE Healthcare), thoroughly washed with deionized water, and equilibrated with 10 mM phosphate buffer (pH 7.0). The adsorbed fraction was eluted with a linear gradient of 0 to 2.0 M sodium chloride, and the fraction containing angiogenin was collected. Then, the fraction was processed by gel filtration chromatography using HiLoad 16/60 Superdex 75 pg (manufactured by GE Healthcare) to obtain 1.8 g of a fraction rich in angiogenin.
- the angiogenin content in the fraction containing a large amount of angiogenin obtained in this way is 10%, and can be used as it is as a sensory improvement agent (Example product 10).
- the column was thoroughly washed with deionized water and then eluted with a linear concentration gradient of 0.1 to 2.0 M sodium chloride.
- the eluted fraction containing angiogenin is fractionated by S-Sepharose cation exchange chromatography (manufactured by GE Healthcare), and the obtained angiogenin-containing fraction is heated at 90 ° C. for 10 minutes and centrifuged. The precipitate was removed by separation.
- this angiogenin-containing fraction was sequentially treated with MonoS cation exchange chromatography, Superose 12 gel filtration chromatography, hydroxyapatite chromatography and C4 reverse phase chromatography to obtain 55 mg of angiogenin.
- the purity of the angiogenin obtained in this way is 99%, and it can be used as it is as a sensory improvement agent (Example product 11).
- Example 11 5 mg of angiogenin obtained in step 1 was dissolved in 10 ml of water, pancreatin (manufactured by Sigma) was added to a final concentration of 0.01% by weight, and enzyme treatment was performed at 37 ° C for 5 hours. And after heat-processing at 90 degreeC for 5 minute (s) and deactivating an enzyme, it lyophilized
- the angiogenin degradation product thus obtained has a molecular weight of 10,000 or less and can be used as it is as a sensory improvement agent (Example Product 12).
- angiogenin degradation product thus obtained has a molecular weight of 10,000 or less and can be used as it is as a sensory improvement agent (Example Product 13).
- Example 1 (Confirmation of cell differentiation promoting activity) 3T3 cells, which are known cell lines of fibroblasts that are known to exist in the skin, were prepared as Example Product 1 and Example Product 3, Example Product 4, Example Product 5, Example Product 7, and Example Product. Nine fractions C, Example product 11 and Example product 13 were added at a concentration of 0.03-1% and cultured for 2 days. As a control, 3T3 cells were cultured for 2 days without the addition of Example products (control). Using these culture supernatants, PC-12 cells, which are neural model cells, were cultured, and morphological differentiation of PC-12 cells was observed when neurotrophic factor was secreted from 3T3 cells.
- PC-12 cells were strongly differentiated from the culture supernatant when the product of Example was added.
- the control culture supernatant did not differentiate PC-12 cells, and no differentiation was observed in observation under an optical microscope in several repeated experiments. From this, it was found that milk-derived proteins and / or milk-derived protein degradation products promote the secretion of neurotrophic factors from 3T3 cells and promote the differentiation of PC-12 cells, which are neural model cells.
- Example 2 (Confirmation of sensory improvement effect by animal experiments) The sensory improvement effect by thermal stimulation was evaluated by a hot plate test which is a behavioral research method for thermal stimulation developed by Woolfe, MacDonald et al. 24-week-old hairless mice (Hos: HR-1) were divided into 13 groups of 6 mice each.
- Example Product 2 and Example Product 6, Example Product 8, Example Product 9, Fraction D, Example Product 10, and Example Product 12 were once a day to give 10 mg and 20 mg, respectively, per 1 kg mouse weight.
- Example Product 2 and Example Product 6, Example Product 8, Example Product 9, Fraction D, Example Product 10, and Example Product 12 were once a day to give 10 mg and 20 mg, respectively, per 1 kg mouse weight.
- the mouse was placed on a 54 ° C. hot plate, and the time until the mouse escaped from the hot plate, standing up, jumping, etc.
- escape behavior was obtained by ingesting 10 mg of fraction D of Example Product 2, Example Product 6, Example Product 8, Example Product 9, Example Product 10, and Example Product 12. There was a tendency for positive reaction time to be shortened, with 20 mg clearly shortening. From this, it is sensed by ingesting fraction D of Example Product 2, Example Product 6, Example Product 8, and Example Product 9, Example Product 10, and Example Product 12, and in particular, peripheral sensation. It has been found that the slowing down can be prevented and improved.
- the Argeometer is designed to cause the same pain when rolling 1 pin (fulcrum 50 g) on the inner side of the upper arm and 2 pin (50 g) on the palm, and was evaluated as follows based on the method of use. In addition, a score was assigned to the evaluation of pain, and an average value was calculated.
- Example Product 1 As shown in Tables 2 to 5, a tendency to improve the feeling of hands and soles by ingesting 10 mg of Example Product 1, Example Product 4, Example Product 7, and Example Product 11 was recognized. , 20 mg clearly improved. Usually, by taking 10 mg or more, preferably 20 mg or more, of milk-derived protein and / or milk-derived protein degradation product per day for each adult, improvement in the dullness of sensation, particularly in the periphery, can be expected.
- Example Product 14 As shown in Tables 7 to 10, the application of the cosmetic product for improving sensation (cream) of Example Product 14 showed a tendency to improve the sensation of hands and soles. From this, it was found that the application of the cream containing the sensation improving agent of the present invention can be expected to improve the sensation, particularly the peripheral sensation.
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Abstract
Description
れた神経栄養因子による、神経モデル細胞であるP-12細胞の形態的な分化を促進することが報告されている(非特許文献1)。神経モデル細胞の形態的な分化の促進は、末梢での感覚鈍化の改善効果を示唆するものである。しかし、上述のセラミドや酵素は食品成分ではないことから、その使用に際しては安全性を検討する必要がある。このような状況の下、より安全で、日常的な摂取あるいは皮膚への塗布によって、末梢での感覚の鈍化を改善する効果のある剤が求められている。
(1)乳由来タンパク質及び/または乳由来タンパク質分解物を有効成分とする感覚改善剤。
(2)前記乳由来タンパク質が、ラクトパーオキシダーゼ、ラクトフェリン、シスタチン、アンジオジェニンから選択されるいずれか1種以上であることを特徴とする(1)記載の感覚改善剤。
(3)前記乳由来タンパク質分解物が、乳由来タンパク質を、タンパク質分解酵素によって分解して得られたものであることを特徴とする(1)乃至(2)記載の感覚改善剤。
(4)前記タンパク質分解酵素がペプシン、トリプシン、キモトリプシン、パンクレアチンよりなる群から選択されるいずれか1種以上であることを特徴とする(3)記載の感覚改善剤。
(5)(1)及至(4)のいずれかに記載の成分を配合した感覚改善用飲食品又は飼料、化粧品。
(6)
乳由来タンパク質及び/または乳由来タンパク質分解物を哺乳動物に摂取させ、または皮膚に塗布することにより、哺乳動物の感覚を改善する方法。
(7)
哺乳動物がヒトであり、乳由来タンパク質及び/または乳由来タンパク質分解物を成人一人一日あたり10mg以上摂取させることを特徴とする(6)に記載の方法。
7℃で5時間酵素処理した。そして、90℃で5分間加熱処理して酵素を失活させた後、凍結乾燥してラクトフェリン分解物0.8gを得た。なお、このようにして得られたラクトフェリン分解物の分子量は、10,000以下であり、そのまま感覚改善剤(実施例品5)として使用可能である。
(細胞分化促進活性の確認)
皮膚に存在することが知られている繊維芽細胞の細胞株である3T3細胞を、実施例品1および実施例品3、実施例品4、実施例品5、実施例品7、実施例品9の画分C、実施例品11、実施例品13を0.03~1%の濃度で添加した状態で、2日間培養した。また、対照として、3T3細胞を、実施例品を添加しないで2日間培養した(対照)。それら培養上清を用いて神経のモデル細胞であるPC-12細胞を培養し、3T3細胞から神経栄養因子が分泌された場合のPC-12細胞の形態的な分化を観察した。
(動物実験による感覚改善効果の確認)
Woolfe,MacDonaldらが開発した熱刺激に対する行動学的研究法であるホットプレート試験にて熱刺激による感覚改善効果を評価した。24週齢のヘアレスマウス(Hos:HR-1)を6匹ずつ13群に分けた。実施例品2および実施例品6、実施例品8、実施例品9の画分D、実施例品10、実施例品12をマウス体重1kgあたりそれぞれ10mg、20mgになるよう1日1回ゾンデで経口投与する、あるは、いずれの実施例品も含まない溶媒のみを1日1回ゾンデで経口投与(対照;0mg)して4週間飼育した。投与終了時に54℃のホットプレートにマウスを置き、マウスがホットプレートから足を離す、立ち上がる、ジャンプするなどの逃避行動までの時間を測定した。熱刺激の最大強度を30秒に設定し、このときの値は30秒とした。その結果を表1に示す。
(経口摂取による感覚改善効果の確認)
手の感覚の鈍化を感じている健康な高齢者(平均年齢75±3歳)を10名ずつ、9群に分けた。それぞれを、いずれの実施例品も摂取しない群(A群)、実施例品1を10mg摂取する群(B群)、20mg摂取する群(C群)、実施例品4を10mg摂取する群(D群)、20mg摂取する群(E群)、実施例品7を10mg摂取する群(F群)、20mg摂取する群(G群)、実施例品11を10mg摂取する群(H群)、20mg摂取する群(I群)とし、6週間摂取してもらった。摂取前と6週間の摂取終了後に表在知覚計アルゲジオメーター(インタークロス社製)を用い、上腕内側の痛覚を基準として手掌と足底土踏まずの痛覚を使用方法に基づき正常、低下I~IIIの計4段階で測定した。その結果を表2、表3に示す。また、6週間の摂取終了後に、それぞれの高齢者に、手の感覚の改善についてアンケート調査を実施した。その結果を表4、表5に示す。
(測定方法)
5種類の太さの違うピンと5つの支点位置で痛覚を評価した。まず、最も細い1pinを上腕内側に転がし、正常な痛覚の度合いを被験者に確認した。次に、手掌と足底に1pinにてホルダを持つ支点の位置を順に変えて転がし、最初に感じた痛覚と同程度の痛みを感じる支点の位置を探した。
(評価方法)
アルゲジオメーターは上腕内側で1pin(支点50g)を転がした場合と、手掌での2pin(50g)で同じ痛みを生じる用に設計されており、使用方法に基づき、以下のように評価した。また、痛みの評価に点数をつけ、平均値を算出した。
2pin(50g)で同じ痛みであれば、正常(0点)
1pin(50g)で同じ痛みであれば、低下I(1点)
1pin(60g)で同じ痛みであれば、低下II(2点)
1pin(70g)で同じ痛みであれば、低下III(3点)
実施例3で得られたラクトパーオキシダーゼ分解物(実施例品3)を使用し、表6に記載される割合で原料を混合し、感覚改善用化粧品(クリーム)を製造した。
(皮膚への塗布による感覚改善効果試験)
手の感覚の鈍化を感じている健康な高齢者(平均年齢75±3歳)を15名ずつ、A群、B群の2群に分けた。A群では実施例品14と同様の方法で製造した、感覚改善剤を含まない化粧品(クリーム)を、B群では、実施例品14の感覚改善用化粧品(クリーム)を1日1回手と足の全体へ塗布した。塗布期間は6週間とし、塗布前と6週間の塗布終了後に表在知覚計アルゲジオメーター(インタークロス(株)社製)を用い、上腕内側の痛覚を基準として手掌と足底土踏まずの痛覚を使用方法に基づき正常、低下I~IIIの計4段階で測定した。その結果を表7、表8に示す。また、6週間の塗布終了後に、被験者それぞれに、手の感覚の改善についてアンケート調査を実施した。その結果を表9、表10に示す。なお、測定方法については試験例3と同様に行った。
実施例品5のラクトフェリン分解物5gを4995gの脱イオン水に溶解し、TKホモミクサー(TKROBO MICS;特殊機化工業社製)にて、6000rpmで30分間撹拌混合してラクトフェリン分解物100mg/100gのラクトフェリン分解物溶液を得た。このラクトフェリン分解物溶液5.0kgに、カゼイン4.0kg、大豆タンパク質5.0kg、魚油1.0kg、シソ油3.0kg、デキストリン18.0kg、ミネラル混合物6.0kg、ビタミン混合物1.95kg、乳化剤2.0kg、安定剤4.0kg、香料0.05kgを配合し、200mlのレトルトパウチに充填し、レトルト殺菌機(第1種圧力容器、TYPE:RCS-4CRTGN、日阪製作所社製)で121℃、20分間殺菌して、本発明の感覚改善用液状栄養組成物50kgを製造した。このようにして得られた感覚改善用液状栄養組成物には、すべて沈殿等は認められず、風味に異常は感じられなかった。なお、この感覚改善用液状栄養組成物には、100gあたり、ラクトフェリン分解物が10mg含まれていた。
実施例品8のシスタチン2gを708gの脱イオン水に溶解し、ウルトラディスパーサー(ULTRA-TURRAXT-25;IKAジャパン社製)にて、9500rpmで30分間撹拌混合した。この溶液に、ソルビトール40g、酸味料2g、香料2g、ペクチン5g、乳清タンパク質濃縮物5g、乳酸カルシウム1g、脱イオン水235gを添加して、撹拌混合した後、200mlのチアパックに充填し、85℃、20分間殺菌後、密栓し、本発明の感覚改善用ゲル状食品5袋(200g入り)を調製した。このようにして得られた感覚改善用ゲル状食品には、すべて沈殿等は認められず、風味に異常は感じられなかった。なお、この感覚改善用ゲル状食品には、100gあたり、シスタチンが200mg含まれていた。
酸味料2gを706gの脱イオン水に溶解した後、実施例品11のアンジオジェニン4gを溶解し、ウルトラディスパーサー(ULTRA-TURRAXT-25;IKAジャパン社製)にて、9500rpmで30分間撹拌混合した。マルチトール100g、還元水飴20g、香料2g、脱イオン水166gを添加した後、100mlのガラス瓶に充填し、95℃、15秒間殺菌後、密栓し、感覚改善用飲料10本(100ml入り)を調製した。このようにして得られた感覚改善用飲料には、すべて沈殿は認められず、風味に異常は感じられなかった。なお、この感覚改善用飲料には、100gあたり、アンジオジェニンが400mg含まれていた。
実施例品2のラクトパーオキシダーゼ分解物2kgを98kgの脱イオン水に溶解し、TKホモミクサー(MARKII 160型;特殊機化工業社製)にて、3600rpmで40分間撹拌混合してラクトパーオキシダーゼ分解物を2g/100g含有するラクトパーオキシダーゼ分解物溶液を得た。このラクトパーオキシダーゼ分解物溶液10kgに大豆粕12kg、脱脂粉乳14kg、大豆油4kg、コーン油2kg、パーム油23.2kg、トウモロコシ澱粉14kg、小麦粉9kg、ふすま2kg、ビタミン混合物5kg、セルロース2.8kg、ミネラル混合物2kgを配合し、120℃、4分間殺菌して、本発明の感覚改善用イヌ飼育飼料100kgを製造した。なお、この感覚改善用イヌ飼育飼料には、100gあたり、ラクトパーオキシダーゼ分解物が200mg含まれていた。
表11に示す配合で原料を混合後、常法にしたがって1gに成型、打錠して本発明の感覚改善剤を製造した。なお、この感覚改善剤1g中には、ラクトパーオキシダーゼが100mg含まれていた。
表12に記載される割合で原料を混合し、感覚改善用化粧品(ローション)を製造した。
Claims (7)
- 乳由来タンパク質及び/または乳由来タンパク質分解物を有効成分とする感覚改善剤。
- 前記乳由来タンパク質が、ラクトパーオキシダーゼ、ラクトフェリン、シスタチン、アンジオジェニンから選択されるいずれか1種以上であることを特徴とする請求項1記載の感覚改善剤。
- 前記乳由来タンパク質分解物が、乳由来タンパク質を、タンパク質分解酵素によって分解して得られたものであることを特徴とする請求項1乃至2記載の感覚改善剤。
- 前記タンパク質分解酵素がペプシン、トリプシン、キモトリプシン、パンクレアチンよりなる群から選択されるいずれか1種以上であることを特徴とする請求項3記載の感覚改善剤。
- 請求項1及至4のいずれかに記載の成分を配合した感覚改善用飲食品又は飼料、化粧品。
- 乳由来タンパク質及び/または乳由来タンパク質分解物を哺乳動物に摂取させ、または皮膚に塗布することにより、哺乳動物の感覚を改善する方法。
- 哺乳動物がヒトであり、乳由来タンパク質及び/または乳由来タンパク質分解物を成人一人一日あたり10mg以上摂取させることを特徴とする請求項6に記載の方法。
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US10016481B2 (en) | 2018-07-10 |
KR20140072893A (ko) | 2014-06-13 |
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US20140249094A1 (en) | 2014-09-04 |
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US20160022771A1 (en) | 2016-01-28 |
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