JP2008214200A - Percutaneous mineral water - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide percutaneous mineral water which contains a mineral ingredient, zinc, is excellent in the absorbability of the zinc from the surface of the skin, and is good in the intake of the zinc into cells. <P>SOLUTION: This percutaneous mineral water contains, as an active ingredient, such an organic zinc compound in which the zinc is bound to an organic compound, as represented by formula (I) [wherein, R is H or OH; (n) is an integer of 8 to 12]. When applied to the skins of a human body or the like, the percutaneous mineral water can thereby exhibit various functions of the zinc, wherein the regeneration of tissues is accelerated to promote the cure of wounds, the renewal of the skins, and the like. The absorbability of the zinc from the surface of the skin is excellent, and the intake of the zinc into cells can well be performed. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a mineral water for transdermal use, which contains an organic zinc compound and has various effects such as a wound healing effect.

  Zinc, a metal element, is an essential nutrient that is indispensable for living organisms and plays various roles in animal and plant tissues. Zinc as a mineral component is mainly used in animals in blood, liver, pancreas. It is abundant in kidneys. Zinc plays an important role as a metal component of enzymes such as zinc enzymes such as DNA and RNA nucleotidyl transferase, insulin, alcohol dehydrogenase, uricase, peptidase, and superoxide dismutase. On the other hand, when zinc in the living body is deficient and the function of the enzyme is insufficient, so-called “zinc deficiency” develops. It is deeply related to symptoms such as infectiousness, taste / olfactory disturbance, stomatitis, dermatitis, depression, alopecia, loss of appetite, decreased gonadal function, arteriosclerosis. Therefore, it is extremely important to supply zinc in the living body.

For example, mineral water (also referred to as mineral water) is widely known as a medium that can provide a mineral component including a zinc component in the living body. There has been provided mineral water obtained by mixing an appropriate amount of natural mineral active wave water containing a zinc component extracted from a soil precursor with natural water (see, for example, Patent Document 1). Further, mineral water is provided in which water is brought into contact with basalt and the zinc component extracted from the basalt is contained as a mineral component (see, for example, Patent Document 2).
JP 2003-23973 A ([Claim 1], [0012]) JP 2004-237248 A ([0009], [0017])

  However, there are few types of mineral water containing zinc components that have been provided so far, which are absorbed through the skin and exert the effect of zinc. Since the absorbability from the skin is not always good, improvement has been desired.

  The object of the present invention has been made in view of the above problems, and is mineral water containing zinc, which is a mineral component that can be expected to have various effects, and is excellent in absorbability of zinc from the skin surface. An object of the present invention is to provide a mineral water for transdermal use in which zinc is well taken into cells.

The mineral water for transdermal use according to claim 1 of the present invention is characterized by containing an organozinc compound represented by the following formula (I) as an active ingredient.

(In formula (I), R represents a hydrogen atom or a hydroxy group (hydroxyl group), and n represents an integer of 8 to 12.)
The transdermal mineral water according to claim 2 of the present invention is the transdermal wound healing promoter according to claim 1.

Transdermal mineral water according to the present invention, zinc ^{(64 Zn)} as a mineral component, since the organic compound-containing organozinc compound is coupled with consisting of ethylene oxide adducts of 3-trimethylsilyl-propanol as an active ingredient When applied to the skin of the human body, etc., various functions provided by zinc, such as promoting tissue regeneration to promote wound healing and skin metabolism, The effect of maintaining and beautifying the skin, improving the hair quality and preventing hair loss can be exhibited. In the present invention, since the zinc is bound to a specific organic compound in mineral water, the zinc is excellently absorbed from the skin surface, and the uptake of zinc into cells is favorably performed. Become. Further, the transdermal mineral water of the present invention is a functional water having such various functions, and has low toxicity to the human body and high safety. Due to these effects, the transdermal mineral water of the present invention is most suitable for use as a transdermal wound healing promoter or the like.

Hereinafter, one form of the transdermal mineral water of the present invention will be described. The transdermal mineral water of the present invention contains an organic zinc compound as an active ingredient, and the organic zinc compound has a structure represented by the following formula (I). In addition, in this invention, mineral water (mineral water) refers to the aqueous solution containing the mineral component represented by zinc etc.

(In formula (I), R represents a hydrogen atom or a hydroxy group (hydroxyl group), and n represents an integer of 8 to 12.)
As represented by the formula (I), the organic part of the organozinc compound which is an active ingredient of the percutaneous mineral water of the present invention includes polyethylene glycol represented by the following formula (II) and the following formula (III): Is a structure in which one molecule is formed by an ether bond with 3-trimethylsilylpropanol. And it becomes because zinc which is an inorganic component couple | bonds with the side chain of 3-trimethylsilyl propanol of this organic part. In addition, m in the polyethylene glycol of the formula (II) corresponds to n of the above-described formula (I), and represents an integer of 8 to 12 like the n.

In this way, when zinc ( ⁶⁴ Zn) as a mineral component is combined with an organic compound called an ethylene oxide adduct of 3-trimethylsilylpropanol to form an aqueous solution to obtain mineral water, zinc is absorbed from the skin surface. In addition, it is possible to improve zinc uptake into cells. In addition, since zinc can activate the action of the enzyme, it is also used to activate cell division in the body and promote tissue regeneration. By applying it transdermally, for example, Metabolism can be promoted, and beautiful skin can be obtained because the water retention and moisture retention of the skin are maintained. Furthermore, the hair loss prevention effect by improving hair quality can be expected.

Therefore, zinc ^{(64 Zn)} as a mineral component, since the contained as the organic compound active ingredient organozinc compound is coupled with consisting of ethylene oxide adducts of 3-trimethylsilyl-propanol, is applied in a transdermal such as a human body In this case, various functions provided by the zinc, for example, promoting tissue regeneration, promoting wound healing and metabolism of the skin, maintaining water retention and moisture retention, and making the skin beautiful The effect of improving hair quality and preventing hair loss can be exhibited. In addition, since the zinc is bound with a specific organic compound in mineral water, it has excellent absorbability of zinc from the skin surface in vivo, and good uptake of zinc into cells become. And since the organozinc compound represented by the formula (I) has low toxicity to the human body, it becomes a highly safe transdermal mineral water.

  The organozinc compound represented by the formula (I) is, for example, as described above, an ether of polyethylene glycol represented by the formula (II) or a derivative thereof and 3-trimethylsilylpropanol represented by the formula (III). It can synthesize | combine simply by synthesize | combining the ethylene oxide adduct of 3-trimethylsilylpropanol and combining metallic zinc which is an inorganic component with the side chain of the ethylene oxide adduct of the said 3-trimethylsilylpropanol.

  Moreover, the organic zinc compound represented by the formula (I) may be extracted and purified from natural products by the following means. That is, after freezing raw mineral water obtained in St. George, Utah, USA, etc., a soluble component by ethyl acetate is extracted from the dried component obtained by lyophilization to obtain a highly soluble component of ethyl acetate. Such extraction of soluble components with ethyl acetate is preferably carried out a plurality of times.

  Next, the obtained ethyl acetate highly soluble component is developed and separated by thin layer chromatography (TLC: abbreviation of Thin-Layer Chromatography; the same applies hereinafter), and a predetermined development position (for example, Rf value 0.35 to 0). Extraction of the adsorbent / developing agent at the development position corresponding to .8), and extracting the resulting adsorbent / adhesive agent as an organozinc compound using methyl alcohol as an extract. You can get things. Such a purified product is dissolved in ethyl acetate again, and developed and separated by thin layer chromatography (TLC), whereby a purified product with high purity is obtained.

  The content of the organozinc compound as an active ingredient of the transdermal mineral water is preferably 0.001% by mass or more, more preferably 0.002 to 0.01% by mass with respect to the total transdermal mineral water. % To be present. By setting the content of the organozinc compound in such a range, it can be stably present in mineral water, can efficiently exhibit the effects of zinc as a mineral component, and has good transdermal absorbability. Can be held in a stable state. The content of the organic zinc compound is particularly preferably 0.002 to 0.006% by mass with respect to the whole transdermal mineral water.

  In the preparation of the transdermal mineral water of the present invention, the organic zinc compound represented by the formula (I) obtained as described above is used as a solvent that does not interfere with transdermal application, such as a known mineral water. It may be dissolved to form an aqueous solution.

  The percutaneous mineral water of the present invention has the effects of zinc as described above, and has good absorbability from the skin and uptake into cells in the living body, so that it can be used for humans, pigs, chickens, cows, horses, etc. By applying it through the skin of animals, the zinc component can be efficiently absorbed from the skin, for example, promoting tissue regeneration and promoting wound healing and metabolism of the skin (like wound healing / metabolism promoting agents). Effect). In addition, it maintains the skin's water retention and moisturizing properties to make the skin beautiful (water retention and moisturizing effect), and improves hair quality to prevent hair loss (hair loss prevention effect) be able to.

  In order to apply the transdermal mineral water of the present invention as, for example, a transdermal wound healing promoter, by applying the transdermal mineral water to the affected area about 1 to 3 times a day, Wound healing can be promoted. When other effects are desired to be exhibited, the percutaneous mineral water of the present invention may be applied to the affected area about 1 to 3 times a day.

  EXAMPLES Hereinafter, although this invention is demonstrated further in detail based on an Example and a comparative example, this invention is not limited to the content of this Example etc.

[Example 1]
Preparation of transdermal mineral water:
The transdermal mineral water of the present invention was prepared using the following methods (1) and (2).

(1) Purification of organozinc compounds:
8 L of raw mineral water obtained in St. George, Utah, USA was prepared, frozen, and lyophilized. About 30 g of solute component was contained per liter.

  Using the obtained dry component, the soluble component was extracted with ethyl acetate and dried. Further, the ethyl acetate-soluble component dried to solid was further extracted with a small amount of ethyl acetate to obtain a highly soluble component of ethyl acetate. The obtained ethyl acetate highly soluble component was about 390 mg.

  The obtained ethyl acetate highly soluble component was developed and separated by preparative thin layer chromatography (TLC) under the following conditions. The developed adsorbent / developed fixing agent at the development position of the fraction corresponding to the Rf value of 0.35 to 0.8 on the preparative TLC was peeled off from the substrate with a plastic scraper and collected. A fraction to be an organozinc compound was extracted from the obtained developed adsorbent / fixing agent (cellulose / Honyoshino kuzu) using methyl alcohol as an extract to obtain a crude product.

(Conditions for preparative thin film chromatography)
Thin-layer board: Original (Japan Atomic Energy Research Institute Tokai Research Institute)
Substrate (plate glass)
Developing adsorbent (cellulose microcrystals, Merck, 1.02330)
Adhesive (Honyoshino Kuzu)
Developing solvent: Chloroform / methanol / water = 10/8/1
Deployment distance: 18cm

  The crude product was dissolved in ethyl acetate and separated again by preparative thin film chromatography (TLC) using the following conditions. The developed adsorbent / developed fixing agent at the development position of the fraction corresponding to the Rf value of 0.35 to 0.8 on the preparative TLC was peeled off from the substrate with a plastic scraper and collected. From the obtained developing adsorbent / adhesive (cellulose / Honyoshino kuzu), extract the fraction that becomes an organozinc compound using methyl alcohol as the extract, distill off the methyl alcohol as the extraction solvent, and purify the product ( An organozinc compound represented by the following formula (I ′) was obtained.

(Conditions for preparative thin film chromatography)
Thin-layer board: Original (Japan Atomic Energy Research Institute Tokai Research Institute)
Substrate (plate glass)
Developing adsorbent (cellulose microcrystals, Merck, 1.02330)
Adhesive (Honyoshino Kuzu)
Developing solvent: Chloroform / methanol / water = 10/8/1
Deployment distance: 8cm

  (In the formula (I ′), n represents an integer of 8 to 12.)

(2) Preparation of mineral water for transdermal use:
The organic zinc compound obtained in (1) is added to the whole mineral water as an organic zinc compound in commercially available mineral water (trade name: VOLVIC (registered trademark): Buoy de Dombolvic sampling). The percutaneous mineral water of the present invention was obtained by containing 002% by mass.

[Test Example 1]
Confirmation of wound healing effect:
The wound healing effect of the percutaneous mineral water of the present invention was measured using a commercially available mineral water (trade name: VOLVIC (registered trademark): Buoy de Dome Volvic Water Collection) and pure water as a reference product and a full-thickness incision wound. The formed rat was confirmed as the test animal by the following method.

(Test animal)
After purchasing a 4-week-old BrlHan: WIST strain @Jcl male rat from Nippon Claire Co., Ltd. and conducting a preliminary breeding for about 1 week to confirm that there is no abnormality in the general state, 6 of them were tested animals. Used as test animals A to F). During the preliminary breeding period, the test animals are housed in polycarbonate cages with a soft chip on the floor, and during the test period, each animal is housed in a polycarbonate cage with a stainless steel floor mesh at room temperature of 23 ° C. ± 2 The animals were raised in a breeding room set at 0 ° C. and a lighting time of 12 hours / day. The feed (solid feed for mice and rats: Lab MR stock, manufactured by Nippon Agricultural Industry Co., Ltd.) and drinking water (tap water) were freely ingested.

(Test method)
First, for each of the test animals, a test zone of 3 zones having a size of about 3 cm × 3 cm was set, and after shaving the hair with a clipper, pentobarbital sodium was administered intraperitoneally at a volume of 40 mg / kg. Then, general anesthesia was performed. A full-thickness incision was made for each test animal with a size of about 1.5 cm × 1.5 cm using a scalpel under anesthesia.

  Next, each test section was washed and disinfected with 5 ml each of mineral water for transdermal use (invention product 1), mineral water (control product 1) and pure water (control product 2) prepared in Example 1 (hereinafter referred to as the following). , "Processing"). This treatment was performed once a day for 5 days continuously from the test start date.

  In order to confirm the effect, each test section was photographed with a digital camera on the first, third, fifth and eighth days of the test, and the wound area was obtained using image analysis software (ImageJ, National Institutes of Health USA). Then, the wound area ratio is obtained by setting the wound area on the first day of the test as 100%, and the reduction rate of the wound area ratio is used as an index for wound healing. Were compared and evaluated.

  During the test period, a collar was attached to each neck so that the test animals did not lick their wounds. In addition, the body weight of the test animals was measured at the end of the test. Table 1 shows the body weights of the test animals at the start and end of the test.

(Test animal weight)

  In addition, as statistical processing of the test results, the obtained wound area ratio was subjected to arctangent transformation, and a one-way analysis of variance was performed. If a significant difference was observed in each test section, the Dunnett method was further used. The paired comparison test of the average rank with the water treatment section was performed. The significance level was 5% in all cases. Regarding the change in the wound area ratio, the results of the product 1 of the present invention are shown in Table 2, the results of the control product 1 are shown in Table 3, the results of the control product 2 are shown in Table 4, and wounds 3 days, 5 days and 8 days after the start of the test. The graph which compared the area ratio is shown in FIG. 1, respectively.

(Changes in wound area ratio: Invention product 1)

(Change in wound area ratio: Control 1)

(Change in wound area ratio: Control 2)

  From the results in Table 1, the body weight of the test animals increased without any problem during the test period, and no change in the test animals during the test period was observed.

  Further, from the results shown in Tables 2 to 4 and FIG. 1, on the 3rd and 5th day from the start of the test, the wound area ratios of the product of the present invention, the control product 1 and the control product 2 are not so different. However, on the fifth day from the start of the test, it was confirmed that the wound area ratio of the product of the present invention tends to be reduced.

  On the 8th day from the start of the test, it was confirmed that the wound area ratio of the product 1 of the present invention was reduced as compared with the control product 1 and the control product 2. Therefore, it was confirmed that the product 1 of the present invention has a wound healing effect as compared with the control product 1 and the control product 2 under the test conditions.

It is the figure which showed the graph which compared the wound area ratio 3 days after a test start, 5 days later, and 8 days after.

Claims (2)

A mineral water for transdermal use, which contains an organic zinc compound represented by the following formula (I) as an active ingredient.

(In formula (I), R represents a hydrogen atom or a hydroxy group (hydroxyl group), and n represents an integer of 8 to 12.)   The transdermal mineral water according to claim 1, which is a transdermal wound healing promoter.

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