JP5564205B2 - Skin pruritus improving agent - Google Patents

Description

  The present invention relates to a skin pruritus ameliorating agent containing N-acetylglucosamine as an active ingredient.

  Skin pruritus is generally a symptomatic skin itch that is not seen in the appearance of the skin, but is itchy, and is found in elderly people with reduced skin functions such as sebum and water secretion. Pregnancy pruritus caused by pregnancy and dialysis skin pruritus found in patients undergoing hemodialysis are known. In particular, patients undergoing hemodialysis frequently have persistent and chronic itching symptoms.

  Since itching afflicts patients regardless of day or night, itching is particularly demanded from the medical field from the viewpoint of maintaining and improving the quality of life. However, the cause has not been specified, and conventionally, only symptomatic treatment has been performed to relieve itching using antihistamines, antiallergic agents, steroids, moisturizers and the like. Such symptomatic therapy is not necessarily preferable as a long-term countermeasure because of concern about side effects of these drugs. Therefore, there has been a demand for an agent for improving skin pruritus that can be used safely even if taken for a long time.

  With respect to such a problem, Patent Document 1 described below describes that lactulose, which is an oligosaccharide, is useful for improving skin pruritus in renal dialysis patients. However, until now, there has been no report that N-acetylglucosamine is effective in improving skin pruritus.

Japanese Patent No. 3055948

  An object of the present invention is to provide a skin pruritus ameliorating agent that can be used safely without causing side effects even when taken for a long time.

  As a result of intensive studies to achieve the above object, the present inventors have found that N-acetylglucosamine has an effect of improving skin pruritus, and has completed the present invention.

That is, this invention provides the skin pruritus improving agent which has the following structures.
[1] A skin pruritus ameliorating agent comprising N-acetylglucosamine as an active ingredient.
[2] The skin pruritus ameliorating agent according to [1], which is an oral agent.
[3] The skin pruritus ameliorating agent according to [1], which is an external preparation.
[4] The skin pruritus improving agent according to any one of [1] to [3], wherein the skin pruritus is dialysis skin pruritus.

  According to the skin pruritus improving agent of the present invention, since N-acetylglucosamine is an active ingredient, even if ingested for a long time, it can be safely used without causing side effects. In particular, it is effective in alleviating the symptoms of persistent and chronic itching seen in dialysis patients.

  In the present invention, N-acetylglucosamine is used as an active ingredient for improving skin pruritus. As N-acetylglucosamine, those chemically synthesized may be used, and those prepared from natural products by, for example, the following method can be used.

  In the case of preparing from a natural product, its origin is not particularly limited. For example, a decomposition method using chitin as a raw material using an acid or an enzyme, or a fermentation method using a sugar such as glucose as a raw material (Japanese Patent Laid-Open No. 2003-2003). However, it is preferably obtained by partially hydrolyzing chitin with an acid from the viewpoint of production efficiency, and chitin is partially hydrolyzed with hydrochloric acid. After dehydration by ion exchange membrane electrodialysis, the coexisting glucosamine hydrochloride is adsorbed and removed with an ion exchange resin, and N-acetylglucosamine is liberated by enzymatic decomposition. preferable.

  Chitin used as a raw material is prepared by removing the calcium content by treating the crustacean crust, such as shrimp, crab, krill, etc., with hydrochloric acid, and then removing the protein by sodium hydroxide treatment. Chitin obtained by an acquisition route, a preparation means, etc. can also be used.

  Partial hydrolysis of chitin with hydrochloric acid is carried out by adding 2 to 20 times the amount of chitin mass and reacting at 30 to 60 ° C. for 2 to 8 hours with stirring. More preferably, 3 to 10 times the amount of chitin mass of concentrated hydrochloric acid is added, and the mixture is reacted at 40 to 50 ° C. for 3 to 5 hours with stirring. If the amount of hydrochloric acid added is outside the above range, the decomposition efficiency is deteriorated or the amount of neutralized salt is increased, which takes time for desalting. Moreover, it is not preferable that the reaction temperature and the reaction time are out of the above ranges because the decomposition efficiency deteriorates and the amount of glucosamine hydrochloride produced increases.

  Next, in order to complete the hydrolysis reaction, it is diluted with about the same volume of water as the partially hydrolyzed solution, and an alkaline agent such as 25-50% sodium hydroxide solution is used so that the temperature does not rise. Neutralize to pH 3-7.

  The neutralized partially hydrolyzed solution contains N-acetylglucosamine, chitin oligosaccharides, glucosamine hydrochloride and the like, as well as undegraded insoluble chitin, which is somewhat brownish due to the decomposition of sugar. Decomposed insoluble chitin and coloring can be removed by filtration using a small amount of activated carbon and a filter.

  Then, the neutralized partially hydrolyzed solution is desalted by the method (ion exchange membrane electrodialysis method) described in Japanese Patent No. 2134244 (Japanese Patent Publication No. 5-86399). The ion exchange membrane used for the ion exchange membrane electrodialysis is not particularly limited. For example, Neocepta CL-25T, CM-1 to 2, AM-1 to 3 (all trade names, manufactured by Tokuyama Soda Co., Ltd.), Selemion CMV / AMV (trade name, manufactured by Asahi Glass Co., Ltd.) and the like.

  Next, the desalted partial hydrolysis solution is treated with an ion exchange resin to adsorb and remove glucosamine hydrochloride in the solution. The ion exchange resin treatment is performed by a combination of a strongly acidic ion exchange resin and a weakly basic ion exchange resin. Thereby, the taste is poor compared with N-acetylglucosamine and chitin oligosaccharide, and glucosamine hydrochloride that causes browning of the powder in the spray drying process can be removed very efficiently.

  Specifically, the desalted partially hydrolyzed solution is treated with a strongly acidic ion exchange resin and subsequently treated with a weakly basic ion exchange resin. The processing method may be a column type or a batch type. As the strong acid ion exchange resin, for example, trade name “Diaion SK1-B” (manufactured by Mitsubishi Chemical) can be used, and as the weakly basic ion exchange resin, trade name “Diaion WA-30” (Mitsubishi). Chemical) etc. can be used.

  Next, an enzyme having hydrolytic ability is allowed to act on the chitin oligosaccharide to decompose the chitin oligosaccharide contained in the partially hydrolyzed solution treated with the ion exchange resin to further release N-acetyl-glucosamine. . As such an enzyme, any enzyme capable of degrading chitin oligosaccharide to monosaccharide N-acetylglucosamine may be used. For example, lysozyme, chitinase, chitobiase (β-N-acetyl) Hexosaminidase) and the like. In addition, some lysozyme and chitinase have low hydrolytic ability for disaccharides and trisaccharides of chitin oligosaccharides, so use an enzyme with high hydrolytic ability for low molecular weight oligosaccharides such as chitobiase. Is preferred.

  Commercially available enzymes can be used as the enzyme. For example, lysozyme is generally chicken egg white lysozyme. Examples of the chitinase include enzymes derived from microorganisms such as Streptomyces griseus, Serratia martzens (Sigma), Aeromonas hydrophila (joint spirit), Streptomyces antibiotecus (Calbiochem). It is also possible to use a crude enzyme obtained by culturing a microorganism producing chitin or chitin oligosaccharide-degrading enzyme such as chitinase or chitobiase and extracting the enzyme from this culture. Moreover, many commercially available enzyme preparations (cellulase preparations, pectinase preparations, amylase preparations, protease preparations, etc.) contain chitinase, chitobiase, etc., and these commercially available enzyme preparations can also be used.

  Conditions for the enzymatic degradation reaction of chitin oligosaccharide contained in the partially hydrolyzed solution treated with the ion exchange resin can be appropriately set according to the type of enzyme and the amount of the enzyme, but the sugar composition finally obtained However, it is preferable to set the conditions for the enzymatic decomposition reaction so that N-acetylglucosamine is contained in an amount of 80 to 99% by mass and chitin oligosaccharide 1 to 20% by mass. If the ratio of the chitin oligosaccharide is higher than the above range, the solubility of the saccharide composition in water is reduced, which is unfavorable for use in foods and drinks. In addition, after completion | finish of reaction, what is necessary is just to inactivate an enzyme by heating a reaction liquid etc. Furthermore, you may perform a decoloring process suitably using adsorption agents, such as activated carbon.

  In the present invention, N-acetylglucosamine is selected by a separation membrane by the method described in JP-A-2000-281696 as it is, or after the enzyme reaction and / or after the enzyme reaction. The N-acetylglucosamine can be used with increased purity.

  As mentioned above, skin pruritus is generally a senile symptom observed in elderly people whose skin function such as sebum and water secretion is reduced, although there are no obvious symptoms in the appearance of the skin. It includes cutaneous pruritus, pregnancy pruritus caused by pregnancy, and dialysis cutaneous pruritus found in patients undergoing hemodialysis.

  The skin pruritus improving agent of the present invention can be used for improving the above-mentioned skin pruritus. In particular, in patients undergoing hemodialysis, symptoms of persistent and chronic itch are frequently observed, but can be preferably used for the improvement of such dialysis skin pruritus. It can also be used to improve the symptoms of more general itching (pruritus) that are not classified into these categories.

  Since N-acetylglucosamine has been confirmed to be absorbed both orally and dermally, the skin pruritus ameliorating agent of the present invention can be taken orally and allowed to act inside the body. Alternatively, it may be applied externally to a place where itching is applied, sprayed, poultice, etc. so that it acts externally from the outside of the body.

  When orally ingesting the skin pruritus ameliorating agent of the present invention, it varies depending on the ingestion form, but preferably contains 1 to 99% by mass of N-acetylglucosamine in terms of solid content in the whole, It is more preferable to contain 1-80 mass%, and it is most preferable to contain 1-60 mass%. The intake is about 0.1 to 15 g, more preferably about 0.3 to 5 g per day for an adult. If the intake of NAG is less than 0.1 g, the effect of improvement cannot be expected, and if it exceeds 15 g, symptoms such as loose stool and diarrhea may occur depending on the constitution, which is not preferable. Moreover, when using as an external preparation, although it changes also with the dosage form, it is preferable to contain 0.0001-60 mass% of N-acetylglucosamine in conversion in solid content in the whole, 0.05- The content is more preferably 20% by mass, and most preferably 0.01 to 10% by mass. The number of times of application may be 1 to several times per day, preferably 1 to 20 times, more preferably 1 to 5 times.

The skin pruritus improving agent of the present invention is a tablet, granule, powder, liquid, powder, granule, capsule by adding a pharmaceutically acceptable base or carrier to N-acetylglucosamine as necessary. In addition to oral preparations such as preparations and jelly-like preparations, they can be commercialized as external preparations such as ointments, creams, gels, packs, lotions and cosmetics .

  EXAMPLES Hereinafter, the present invention will be specifically described with reference to examples, but these examples do not limit the scope of the present invention.

<Test Example 1>
[Method]
15 hemodialysis patients who complain of itching and are using topical medications to relieve itching were given instructions on skin care, such as how to wash their bodies and how to apply the medicine correctly. In the above, from 2 weeks after the start of the guidance, tablets containing 1000 mg of N-acetylglucosamine were orally taken once a day for 4 weeks. Before and after taking the tablets, a questionnaire was conducted on the items shown in Table 1 below.

[result]
As a result, it was not possible to improve itching only by skin care guidance such as how to wash the body and how to apply the medicine correctly.

  In contrast, when N-acetylglucosamine was ingested, the number of times of topical application was once a day before administration, but it was 0.27 after 4 weeks, and the itch scale was average before administration. What was 1.87 decreased to 0.86 after 4 weeks. In the overall evaluation questionnaire, there were 6 responses that “remarkably effective”, 4 responses that “effective”, and 5 responses that “not effective”, and more than 65% of patients The effect of pruritus improvement was confirmed. In addition, the same tablet which does not contain N-acetylglucosamine was prepared and ingested for 4 weeks, and it was confirmed separately that there was no effect on the itch symptoms before and after the ingestion. Table 2 below summarizes these results.

  From the above, it has been clarified that N-acetylglucosamine has the effect of improving skin pruritus.

Claims (1)

A skin pruritus ameliorating agent characterized by containing N-acetylglucosamine as an active ingredient and being used orally to improve dialysis skin pruritus .