KR102077858B1 - Ceramide and collagen synthesis promoter and collagen saccharification inhibitor - Google Patents

Abstract

By promoting the synthesis of ceramide of the skin, it is possible to increase the barrier function such as the moisture retention function of the skin, and to increase the amount of collagen contained in the skin, and to inhibit the glycation of collagen to prevent wrinkles and sagging of the skin, and also to safely Provide oral solvents for ingestion. The present invention is a ceramide synthesis promoter, collagen synthesis promoter, and collagen glycosylation inhibitor for oral intake of xylitol.

Description

CERAMIDE AND COLLAGEN SYNTHESIS PROMOTER AND COLLAGEN SACCHARIFICATION INHIBITOR}

The present invention relates to promoters for the synthesis of ceramides and collagen and inhibitors of glycation of collagen.

Background Art Conventionally, it is known that problems such as dry skin, wrinkles and sagging occur with aging of the skin and deterioration of the cortex.

Dry skin is a condition where the skin's moisture retention function is reduced, the skin is dried, and the surface becomes dull. Dry skin is susceptible to stimulation from the outside, and roughness, inflammation, rash, eczema, stretch marks, and the like are likely to occur, and thus improvement is required.

As a method of preventing drying of the skin and improving dry skin, a method of applying an external preparation containing a component for inhibiting evaporation of moisture such as petrolatum, mineral oil and ceramide is applied to the skin. Moreover, the method of apply | coating collagen to skin is performed as a method of preventing wrinkles and sagging on skin. However, it is technically very difficult to exert the same moisture retention function as the original skin only by applying such external preparations. In addition, the effect is temporary, there is a question about the continuous effect, there is a problem that does not fundamentally solve dry skin and wrinkles and sagging.

As a method without such a problem, a method of orally ingesting a component that promotes the synthesis of ceramide and collagen in the cells of the skin has been studied.

Ceramides are complex lipids in which acid-bonded sphingosine bases and fatty acids are the major components of keratinocyte lipids in the epidermis. Keratinocyte intercellular lipids play an important role in maintaining the skin's barrier function against water permeation, chemical stimulation, and physical stimulation, and ceramides contribute in particular to the barrier function against water permeation. Therefore, the amount of ceramide contained in the skin is an important index for measuring the moisture retention function of the skin. In dry skin seen in atopic dermatitis and dry skin in the elderly, reduction of ceramide is considered to be one of the causes (Non-Patent Document 1).

Serine palmitoyltransferase (SPT) is known as a rate-limiting enzyme in the biosynthesis of ceramide. SPT is an enzyme that synthesizes 3-ketodihydrosphingosine from serine and palmitoyl-CoA and is the enzyme that catalyzes the first reaction in the biosynthesis of sphingolipids, including ceramide.

On the other hand, collagen, which is one of the extracellular matrices, is a fibrous protein whose basic structural unit is a helical structure composed of three polypeptide chains. The amino acids constituting the collagen are mainly composed of glycine, proline, hydroxyproline, alanine, and the like. Among them, hydroxyproline is an amino acid characteristic of collagen, and thus is an index when quantifying collagen amount.

Collagen plays an important role in maintaining the elasticity of the skin, and the decrease in the amount of collagen and the change in the quality of the collagen are correlated with natural aging with age and light aging due to ultraviolet rays. It is known that it causes. Collagen glycation, one of qualitative changes, is a phenomenon that progresses with age, and is considered to be one of skin aging phenomena recently.

As a ceramide synthesis promoter, nicotinic acid derivative (patent document 1), plant extract (patent documents 2-4), herbal herbal medicine (non-patent literature 2), phospholipid of milk (nonpatent literature 3), Japanese sake component (nonpatent literature 4 ), Niacinamide (non-patent document 5), etc. are disclosed.

As a collagen synthesis promoter, Zymomonas fermentation metabolites (Non Patent Literature 10), plant extracts (Patent Documents 5 to 9), collagen peptide-like dipeptides or tripeptides (Patent Literatures 10 to 11), and γ-orizanol decomposed products ( Patent document 12) etc. are disclosed.

However, some of them are highly irritating to the skin, and some are insufficient in terms of safety. In addition, the effect is evaluated by directly acting the active ingredient on the cultured cells. When considering the use in humans or animals, whether the active ingredient is absorbed in the body or the metabolism of the active ingredient in the body can be effective. It is unclear whether or not there is, and it is not clear whether sufficient effect is obtained. In short, it is hard to say that it is enough in terms of the effect and safety.

Japanese Patent Publication No. 3508042 Japanese Laid-Open Patent Publication 2006-111560 Japanese Unexamined Patent Publication No. 2004-210743 Japanese Unexamined Patent Publication No. 2002-370998 Japanese Unexamined Patent Publication No. 2007-230917 Japanese Laid-Open Patent Publication 2006-273756 Japanese Laid-Open Patent Publication No. 2006-265120 Japanese Laid-Open Patent Publication 2005-139141 Japanese Laid-Open Patent Publication 2005-120108 Japanese Unexamined Patent Publication No. 2010-024200 Japanese Laid-Open Patent Publication 2006-056904 Japanese Laid-Open Patent Publication 2005-263677

 Miyaji Yoshiki et al., Cosmetic Dermatology, 2005, pages 8-18, Nanzan-do  Hino Takayuki, Masahaki Morohashi, Fragrance Journal, 2004, No. 3, pages 26-30, "Review of herbal herbal medicines that regulate lipid metabolism of skin"  Haruta Y. et al., Bioscience, Biotechnology, and Biochemistry, 2008, Vol. 72, No. 8, pages 2151-2157, Dietary phospholipid concentrate from bovine milk improves epidermal function in hairless mice.  Nakahara M. etal., Bioscience, Biotechnology, and Biochemistry, 2007, Vol. 71, No. 2, pages 427-434, Effect of a sake concentrate on the epidermis of aged mice and confirmation of ethyl alpha-D-glucoside as its active component.  Tanno Osamu, Fragrance Journal, 1999, 10, pages 23-28, "Improvement of epidermal barrier function by promoting de novo ceramide synthesis"  Knuuttila M.L. etal., Life Sciences, 2000, Vol. 67, No. 3, pages 283-290, Effects of dietary xylitol on collagen content and glycosylation in healthy and diabetic rats.  Mattila P.T. etal., Gerontology, 2005, Vol. 51, No. 3, pp. 166-169, Effects of a long-term dietary xylitol supplementation on collagen content and fluorescence of the skin in aged rats.  J. F. Woessner, Jr., Arch Biochem Biophys., 93, 440-447 (1961)  I. Bergman and R. Loxley, Anal Chem., 35, 1961-1965 (1963)  Hiroshi Tanaka, Fragrance Journal, 2006, No. 12, pages 29-35, "Damage and Improvement of Dermal Components by Ultraviolet Rays"  Philip G. et al., The Journal of Nutrition, 1993, Vol. 123, No. 11, pages 1936-1951, AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet.

Based on the above-mentioned problems, the present invention can enhance skin barrier function such as skin moisture retention function by promoting the ceramide synthesis of the skin, and also increase skin collagen amount and suppress the glycation of collagen to reduce wrinkles and An object of the present invention is to provide a safe oral oral solvent that prevents sag.

As a result of intensive studies on the above problems, the present inventors have found that by orally ingesting xylitol, the synthesis of ceramide is promoted and the mRNA expression level of serine palmitoyltransferase is increased. In addition, the present inventors found that the amount of collagen in the skin is increased by oral ingestion of xylitol, and the glycosylation of collagen is suppressed. Based on these findings, the present inventors have completed the present invention.

In other words, the present invention relates to an oral ingestion of ceramide and collagen synthesizing agent containing xylitol as an active ingredient and an inhibitor of saccharification of collagen.

By oral ingestion of xylitol, the amount of ceramide synthesis and the amount of collagen in the skin can be increased, and the glycated collagen level can also be reduced.

In addition, xylitol has conventionally been used as a sweetener such as confectionery, and there is no problem with regard to its safety even if taken orally.

1 is a schematic of a test schedule in an example.
Fig. 2 is a graph showing the expression level of the serine palmitoyltransferase gene (Spt) in the 3-month test group in Test Example 1;
3 is a graph showing the expression level of the serine palmitoyltransferase gene (Spt) in the test group of 6 months in Test Example 1. FIG.
4 is a graph showing measurement results of ceramide levels in a 3-month test group in Test Example 2. FIG.
5 is a graph showing measurement results of ceramide levels in a 6-month test group in Test Example 2. FIG.
6 is a flowchart of extraction and fractionation in Test Example 3. FIG.
7 is a graph showing the amount of hydroxyproline in a test group of 3 months in Test Example 3. FIG.
8 is a graph showing the amount of hydroxyproline in a six-month test group in Test Example 3. FIG.
9 is a graph showing the fluorescence intensity per collagen amount in a 3-month test group in Test Example 3. FIG.
10 is a graph showing the fluorescence intensity per collagen amount in a 6-month test group in Test Example 3. FIG.

Xylitol is a sugar alcohol having 5 carbon atoms and is also called xylite. It is produced by the hydrogenation of xylose and is widely used in sweets such as chewing gum and candy as a sweetener without caries.

Xylitol is one of polyols, such as glycerin and propylene glycol, and since it is high in water retention power and can be expected to improve the water retention function by apply | coating to skin, it may be mix | blended as a moisturizing component of an external preparation. However, such an effect can be expected when used externally, and even when ingested orally with xylitol, it is not possible to reach the skin as it is and exhibit such an effect.

As for the effect on the skin when orally ingested xylitol, in the experiments with rats containing xylitol mixed containing relatively high doses of xylitol at 5.0% by weight and 10.0% by weight, the amount of collagen in the skin is increased, and also collagen The effect of suppressing glycosylation of has been reported (Non Patent Literature 6 and Non Patent Literature 7). However, there was no knowledge about the effect on skin ceramide synthesis. In addition, as for the effects on collagen, when a human ingests a large amount of sugar alcohol, including xylitol at once, there are concerns about side effects such as diarrhea, and thus an evaluation on whether the same effect can be expected with a lower content of xylitol. Is desired.

In contrast, the present inventors have found that by orally ingesting xylitol, the synthesis of ceramide of the skin is promoted, and the mRNA expression level of serine palmitoyltransferase (SPT), which is a rate-limiting enzyme in ceramide biosynthesis, is increased. . In addition, the present inventors have conventionally found that the amount of collagen in the skin is increased by oral ingestion of a small amount of xylitol, and the glycosylation of collagen is suppressed. Based on these findings newly obtained, the present inventors completed the ceramide synthesis promoter, collagen synthesis promoter and collagen glycation inhibitor according to the present invention.

The ceramide synthesis promoter, collagen synthesis promoter, and collagen glycation inhibitor of the present invention are preferably effective amounts of xylitol in an amount of 0.4 g to 1.35 g per 100 kcal of calorie consumed in a daily diet of a blood donor. It contains as a component. More preferably, xylitol is contained as an active ingredient in an amount of 0.4 g to 0.67 g per 100 kcal of calorie ingested per day of a blood donor. The ceramide synthesis promoter, collagen synthesis promoter and collagen glycation inhibitor of the present invention preferably contain xylitol in an amount of 0.1% by weight to 99% by weight as the active ingredient, and more preferably 1% by weight to It contains in the ratio of 90 weight%.

Moreover, the ceramide synthesis promoter, collagen synthesis promoter, and collagen glycation inhibitor of the present invention are characterized by being taken orally.

The ceramide synthesis promoter, collagen synthesis promoter, and collagen glycation inhibitor of the present invention can be used, for example, as a drug, quasi-drug or food or drink.

In the case of pharmaceuticals, it is administered as an oral drug. Examples of the formulation of the oral preparation include tablets, capsules, powders, syrups, drinks, and the like. In the case of quasi-drugs, it is used in the formulation of tablets, capsules, drinks. In the case of food and drink, beverages, such as a drink, foods, such as candy, senbei, and cookies, the favorite goods, such as tobacco and chewing gum, feed and feed, or cosmetics, such as gargle and toothpaste, are mentioned. In addition, these are only the examples and the present invention can be used for any article as long as the xylitol can be taken orally.

In the case of a drug or quasi-drug, it may contain one or two or more pharmacologically acceptable carriers and, if necessary, an active ingredient for other treatments. In addition, excipients, binders, disintegrants, lubricants, dispersants, surfactants, plasticizers, suspending agents, emulsifiers, diluents, buffers, antioxidants, bacterial inhibitors and the like may be contained.

Moreover, the food-drinks may contain the base material, support | carrier, excipient, additive, extender, coloring agent, fragrance | flavor, etc. which are accept | permitted in food manufacture.

In addition, the components other than xylitol are not limited to the above, and the present invention may optionally contain any known components.

Xylitol-containing ceramide synthesis promoters, collagen synthesis promoters, and collagen glycation inhibitors of the present invention can be prepared by any method known in the art. In the manufacturing process, xylitol may be added by any known method.

Moreover, the ceramide synthesis promoter, collagen synthesis promoter, and collagen glycosylation inhibitor containing xylitol of the present invention can be used not only for humans but also for animals other than humans (hereinafter, abbreviated as non-human animals). Non-human animals include animals other than humans, such as mammals, reptiles, amphibians, and fish.

According to the above structure, in this invention, the synthesizing effect of the ceramide of the same grade as the ceramide synthesis promoter ingested by the conventional oral can be expected. Therefore, it can use for the use which improves the moisture retention function of skin, improvement of dry skin, etc. Moreover, in this invention, the effect agent which accelerates | stimulates the synthesis | combination of collagen, and the effect which suppresses glycosylation of collagen can also be anticipated. Therefore, it can be used for the use which prevents wrinkles and sagging of skin.

Example

EMBODIMENT OF THE INVENTION Although this invention is demonstrated using an Example below, these Examples do not limit the scope of the present invention at all.

Public animals, breeding of animals

40 SD rats (male, 11-week-old, growth weight at the time of plant shipment: 350-400 g) were purchased from Japanese urea and used for the experiment. Animals were reared in a convention animal breeding room under an environment of room temperature 23 ± 1 ° C., humidity 50 ± 10%, and light and dark cycles for 12 hours (8 to 20:00). After 2 weeks of lean breeding, the weight was measured, and the rats were divided into four test groups shown in Table 1 so that the average weight of each group was equal, and then, breeding was conducted for 11 weeks as the test feed administration period. Based on body weight after 11 weeks, groups were divided into 3 and 7 so that the average weight in each test group was equalized. The group divided into three animals was again dissected by breeding for one week only (12 weeks in total, three months test group). The group divided by seven was further reared for 13 weeks and dissected (24 weeks total, 6 months trial group). The outline of a test schedule is shown in FIG.

Feed was based on AIN-93G standard tablet feed. Feed having a composition in which sucrose was replaced with xylitol (see Table 2) was prepared and used for the test. In addition, the same feed as the control group was given during purified breeding. In addition, since the value of 2.40 kcal / g and 3.00 kcal / g is generally accepted about the calorie of xylitol, Table 2 shows the result calculated based on both values.

Feed and water were freely ingested, and 18 hours of 16:30 to 10:30 of the next day was taken as a feeding time from one week before dissection, and fasted between 10:30 and 16:30. The weight measurement and the amount of feed and residual amount were carried out once every two days, and the difference between them was taken as the feeding amount. Moreover, the presence or absence of abnormality, such as a stool state and diarrhea, was observed and recorded.

Two to three weeks after the test breeding, one animal of the xylitol 5% horned group had a traumatic injury due to a dorsal behavior of the back and was healed afterwards, but the effect on the interpretation of the skin was considered, so this animal was excluded from the analysis. Moreover, at the 10th week of test breeding, one animal of the xylitol 1.5% mixed group was confirmed with hematuria, and since the body weight was not stabilized, this animal was removed from the analysis subject.

Results about breeding

One to ten rats of the xylitol 5.0% mixed group were identified with soft stools (water-rich stools) for one to two days from the start of the test feed administration, but they recovered temporarily afterwards. In addition, there was no statistical difference in the amount of feeding between the groups through the breeding period in the change of the average weight of rats in each group during the three-month breeding period, the change in the total average feeding amount for one week, and the cumulative feeding amount for three months.

Anatomy, collection of each sample

The dissection was performed by administering the anesthetic drug Somunopentyl (Kyoritsu Pharmaceuticals) intraperitoneally in 0.1 ml per 100 g of body weight. After anesthesia, the hair of the rat back was shaved with a barrican, and then, a slide glass coated with an instant adhesive (aron alpha) was affixed on the back surface for 1 minute to collect sebum on the skin surface. Thereafter, back skin (part of the skin was cut into circles with a punch of φ = 1.8 cm), plasma (heart blood collection), liver and epididymal fat were collected.

Test Example 1 Measurement of Expression Level of Ceramide Synthetic Enzyme

Total RNA Extraction from the Skin and cDNA Preparation

The collected skin tissue was broken in a frozen state, and about 350 mg of the broken skin pieces were provided as a sample. Extraction of total RNA from skin tissue was performed using SV Total RNA Isolation System (Promega). cDNA was prepared by Reverse Transcription Reaction (High Capacity cDNA Reverse Transcription Kit, ABI) from 2 μg total RNA. The prepared cDNA was diluted 5-fold with sterile water for use in the analysis by real-time PCR.

Analysis of various gene expressions by real-time PCR

24 μl of a real-time PCR reaction solution containing a primer and a probe of serine palmitoyltransferase (Spt) and a TaqMan Universal Master Mix II (ABI) in a 96 well tube (ABI); 1 µl of the prepared cDNA 5-fold dilution sample was added, and gene expression analysis was performed by real-time PCR (type 7300, ABI). Primers and probes used the arrangement shown below. In addition, FAM was coupled to the 5 'end of the oligo DNA used for the probe, and TAMRA was coupled to the 3' end. The amount of mRNA was corrected by the expression level of β-actin, which is a housekeeping gene, and then calculated as a relative value with respect to the control group.

Forward primer: 5'-CAG TGC AGC CTG CTT TGC TA-3 '(array number 1)

Reverse primer 5＇-GCC TTT CGA GGA TTC TTT TGA TC-3 ＇(SEQ ID NO: 2)

Probe (rat SPT): 5'-CCA GAA AGG ACT ACA GGC ATC ACG CAG-3 '(array number 3)

Measurement result of expression level of serine palmitoyltransferase gene (Spt)

The expression level of the serine palmitoyltransferase gene (Spt) in the 3 month test group is shown in FIG. 2, and the expression level of the serine palmitoyltransferase gene (Spt) in the 6 month test group is shown in FIG. Represent each.

No statistically significant differences and trends were observed between the groups, but all of the xylitol-administered groups had higher expression levels than the control group.

Test Example 2 Measurement of Skin Ceramide Amount

Extraction of Skin Ceramides

The sebum sample collected on the slide glass from the dorsal skin surface at the time of dissection was immersed in the solvent which mixed hexane: ethanol in 95: 5, and the lipid component was extracted by ultrasonication. The extracted lipid component was filtered through a hydrophobic filter (Millex (registered trademark) -FH, φ = 0.45 µm, myripoa), transferred to a test tube, and concentrated and dried with nitrogen gas. The dried lipid component was dissolved again in chloroform, transferred to a dark brown microtube, and concentrated and dried again with nitrogen gas. At this time, the weight of the microtube was measured beforehand, and the difference with the weight after concentration and drying with nitrogen gas was made into the total lipid amount.

10 µl of chloroform was added per 1 mg of the total lipid obtained, and the lipid component was dissolved to obtain a total lipid sample provided to the TLC method.

Quantification of Skin Ceramide Amount by TLC Method

5 μl (0.5 mg of total lipid equivalent) of the total lipid sample was spotted onto a silica gel plate (HPTLC, Merck) and developed with a developing solvent (chloroform: methanol: acetic acid = 192: 7: 1). After completion of the development, the silica gel plate was sufficiently dried, and then, the copper sulfate (II) -phosphate solution (coloring reagent) prepared according to the formulation shown in Table 3 was sprayed, and heated at 150 ° C. for about 10 minutes. Cerebellum-derived ceramide (Ceramide, Natural Mixture, Funakoshi) was used as a sample. Spots appearing on silica gel plates were quantified with an image analyzer (LAS-3000, Fujifilm).

Measurement result of skin ceramide level

The measurement result of the ceramide level in a 3 month test group is shown in FIG. No statistically significant differences and trends were observed between the groups, but the xylitol-administered group showed higher values than the control group as a whole, and the xylitol 2.5% mixed group was higher than the control group.

The measurement result of the ceramide level in a 6-month test group is shown in FIG. The xylitol 1.5% and 5.0% groups were significantly increased 1.4-1.5 times compared with the control group. No statistically significant differences and no significant trends were found in the xylitol 2.5% mixed group, but they were higher than the control group.

TEST EXAMPLE 3 Evaluation of Skin Collagen Amount and Measurement of Saccharified Collagen Amount in Collagen

Extraction, fractionation of total collagen

Extraction and fractionation were performed according to the nonpatent literature 8 (refer FIG. 6).

The collected skin was freeze-broken, degreased and dehydrated with acetone, and cut with anatomical scissors. Thereafter, freeze-pulverization was performed with a ball mill (Retsch), and freeze-dried to obtain a skin powder sample. 9 ml of 0.5 M acetic acid was added to 30 mg of the skin powder sample, and after shaking extraction at 4 ° C. for 16 hours, the mixture was centrifuged at 30,000 G and 4 ° C. for 30 minutes, and the mixture was separated into supernatant and precipitate.

Pepsin 1: 10,000 (for biochemical, Wako Pure Co., Ltd.) was added to the supernatant so as to have a final concentration of 100 mg / ml, and reacted at 22 ° C for 16 hours to decompose the non-collagenic protein. Thereafter, sodium chloride was added so as to have a final molar concentration of 1.8 M, and further centrifuged at 30,000 G, 10 minutes at 4 ° C, and the resultant precipitate was dissolved in 0.1 M acetic acid as an acid-soluble fraction.

On the other hand, the precipitate after 0.5 M acetic acid extraction was washed once with the collagenase buffer prepared in the composition of Table 4, and then 3 ml of the collagenase enzyme solution prepared at the concentration of 200 unit / ml in the composition of Table 5 was added. And it reacted at 37 degreeC for 22 hours. Then, centrifugation was performed at 30,000 G, 30 minutes, and 4 degreeC, and the supernatant was made into the collagenase soluble fraction.

Determination of Hydroxyproline (Hyp)

Hydroxyproline was quantified in accordance with Non-Patent Document 8 and Non-Patent Document 9.

500 µl of 6N hydrochloric acid was added to 20 µl of the acid-soluble fraction or the collagenase-soluble fraction, followed by mixing, followed by acid hydrolysis at 130 ° C for 3 hours. After cooling, 2 µl of 0.04% methyl red solution was added as a pH indicator, and 1150 µl of 2.5 N sodium hydroxide was added. The dilute aqueous solution of hydrochloric acid and sodium hydroxide was suitably added, and pH was adjusted to 6-7 so that the color of a solution might become a color of pink and pale yellow.

Then, 1 ml of the 50 mM chloramine T solution prepared with the composition of Table 6 and Table 7 was mixed, after reaction for 20 minutes at normal temperature, 1 ml of 18.9% perchloric acid aqueous solution was mixed, and it was made to react at room temperature for 5 minutes. Then, 1 ml of the 20% p-dimethylaminobenzaldehyde solution prepared by the composition of Table 8 was mixed, and it was made to react for 20 minutes in 60 degreeC hot water bath. Thereafter, the mixture was cooled with running water for 5 minutes, and stopped at room temperature for at least 1 hour. Then, the absorbance at 557 nm was measured with a spectrophotometer (U-3900H, Hitachi), and the amount of hydroxyproline was determined from the calibration curve. Thus, the value which multiplied the conversion factor 7.25 by the amount of hydroxyproline obtained was made into the collagen conversion value.

Measurement of fluorescence intensity and evaluation of glycated collagen amount

According to the nonpatent literature 6, the fluorescence intensity measurement was performed. The acid-soluble fraction and the collagenase-soluble fraction were diluted appropriately, and the fluorescence intensity was measured at the excitation wavelength Ex: 370 nm and the measurement wavelength Em: 440 nm with a fluorescence spectrophotometer (RF-5000, Shimadzu Corporation). The fluorescence intensity per collagen amount calculated from the amount of hydroxyproline in each fraction was calculated and used as an index of glycated collagen amount.

The measurement result of the amount of hydroxyproline

The amount of hydroxyproline in a 3 month test group is shown in FIG. 7, and the amount of hydroxyproline in a 6 month test group is shown in FIG.

For the 3-month test group, no statistically significant differences and significant trends were found between the groups for both the acid-soluble fraction and the collagenase-soluble fraction, whereas for the 6-month test group, the amount of hydroxyproline increased in any fraction. In particular, in the collagenase soluble fraction, all of the xylitol mixed groups were significantly increased compared with the control group. Since the amount of hydroxyproline, an amino acid characteristic of collagen, increases, it is thought that the amount of collagen synthesized increased in the xylitol mixed group.

Measurement result of glycated collagen level

The fluorescence intensity (glycosylated collagen level) of the amount of collagen calculated from the amount of hydroxyproline in the three-month test group is shown in FIG. 9, and the fluorescence intensity (glycosylated amount of the amount of collagen calculated from the amount of hydroxyproline in the six-month test group. Collagen levels) are shown in FIG. 10, respectively.

A decrease in glycated collagen levels was seen in any fraction, especially for the 3-month test group, in the collagenase soluble fraction, the xylitol 2.5% group was significantly lower than the control. In addition, for the 6-month test group, the values of all the xylitol mixed groups (1.5%, 2.5%, 5.0%) were significantly lower than the control group in both fractions of acid solubility and collagenase solubility.

As described above, in the xylitol-administered group, the synthesizing promoting effect of ceramide was observed as compared with the control group which did not administer xylitol. Moreover, even when compared with patent documents 1-4 and nonpatent literatures 2-5 which are prior documents which disclose the result of oral ingestion of components other than xylitol, it was confirmed that it has the same synthetic effect.

Moreover, compared with the control group, the xylitol administration group showed the effect of promoting the synthesis of collagen and the effect of inhibiting the glycosylation of collagen.

Example 4

Tablets were prepared according to the following prescription.

Xylitol 40%

25% crystalline cellulose

Lactose 25%

Corn starch 8%

Magnesium Stearate 2%

The said component was mixed uniformly and the mixed powder was refine | purified by tableting.

Example 5

Tablets were prepared according to the following prescription.

Xylitol 80%

Lactose 8%

10% of hydroxypropyl cellulose

Magnesium Stearate 2%

The said component was mixed uniformly and the mixed powder was refine | purified by tableting.

Example 6

The syrup was prepared according to the following prescription.

Sweet syrup 30%

Xylitol 20%

Purified water 50%

Example 7

A capsule was prepared according to the following prescription.

Xylitol 99%

Magnesium stearate 1%

The ingredients were mixed uniformly and the mixed powder was filled into hard capsules.

Example 8

A capsule was prepared according to the following prescription.

Xylitol 90%

Lactose 8%

Magnesium Stearate 2%

The ingredients were mixed uniformly and the mixed powder was filled into hard capsules.

Example 9

The powder was prepared according to the following prescription.

Xylitol 65%

Corn starch 9.9%

Hydroxypropyl cellulose 25%

l-menthol 0.1%

Example 10

The drink was prepared according to the following prescription.

Xylitol 5%

Acidulant 1.2%

Fructose glucose liquid 6%

Fragrance 0.1%

Purified water 87.7%

Example 11

The drink was prepared according to the following prescription.

Xylitol 1%

Acidulants 1.4%

Fructose glucose liquid 8%

Fragrance 0.1%

Purified water 89.5%

Example 12

The drink was prepared according to the following prescription.

Xylitol 0.1%

Acidulant 1.2%

2% sugar

Fructose glucose liquid 8%

Fragrance 0.2%

Purified water 88.5%

This application claims the priority from Japanese Patent Application No. 2009-262951 for which it applied on November 18, 2009, and quotes the content as a part of this application.

                        SEQUENCE LISTING <110> LOTTE CO., LTD. et al.   <120> Synthesis Promoter of Ceramide and Collagen, and Glycosylation Inhibitor of Collagen <130> LOTTE-128WO <150> JP 2009-262951 <151> 2009-11-18 <160> 3 <170> PatentIn version 3.5 <210> 1 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Forward Primer <400> 1 cagtgcagcc tgctttgcta 20 <210> 2 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Reverse Primer <400> 2 gcctttcgag gattcttttg atc 23 <210> 3 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Probe <400> 3 ccagaaagga ctacaggcat cacgcag 27

Claims (12)

Drinks, candy, senbei characterized by promoting the synthesis of ceramides containing xylitol as an active ingredient in an amount of 0.4 g to 0.67 g per 100 kcal of calorie consumed in a daily diet of a blood donor Food composition for maintaining skin moisture having any one of the formulations selected from the group consisting of, cookies, tobacco, and chewing gum. The method of claim 1,
A food composition for maintaining skin moisture, comprising 1.5% by weight to 2.5% by weight of xylitol. Drinks, candy, senbei characterized by promoting the synthesis of collagen, containing xylitol as an active ingredient in an amount of 0.4 g to 0.67 g per 100 kcal of calorie consumed in a daily diet of a blood donor Skin, anti-aging food composition having any one formulation selected from the group consisting of cookies, tobacco, and chewing gum. The method of claim 3, wherein
A food composition for preventing skin aging, comprising 1.5% by weight to 2.5% by weight of xylitol. Drinks, candy, senbei containing xylitol as an active ingredient in an amount of 0.4 g to 0.67 g per 100 kcal of calorie consumed in a daily diet of a blood donor, and suppressing saccharification of collagen Skin, anti-aging food composition having any one formulation selected from the group consisting of cookies, tobacco, and chewing gum. The method of claim 5, wherein
A food composition for preventing skin aging, comprising 1.5% by weight to 2.5% by weight of xylitol. Tablets, capsules, characterized in that it contains xylitol in an amount of 0.4 g to 0.67 g per 100 kcal calorie consumed in a daily diet of a blood donor, and promotes the synthesis of ceramide, A pharmaceutical composition for the prophylaxis, treatment or prophylaxis and treatment of atopic dermatitis or dry skin for oral ingestion having any one formulation selected from the group consisting of a powder, a syrup, and a drink. The method of claim 7, wherein
A pharmaceutical composition for the prevention, treatment or prophylaxis and treatment of atopic dermatitis or dry skin for oral intake, characterized by containing 1.5% by weight to 2.5% by weight of xylitol. Tablets, capsules, characterized in that it contains xylitol as an active ingredient in an amount of 0.4 g to 0.67 g per 100 kcal of calorie consumed in a daily diet of a blood donor, and promotes the synthesis of collagen, A pharmaceutical composition for preventing skin aging for oral intake having any of the formulations selected from the group consisting of powders, syrups, and drinks. The method of claim 9,
A pharmaceutical composition for preventing skin aging, comprising 1.5% by weight to 2.5% by weight of xylitol. Tablets, capsules, characterized in that it contains xylitol as an active ingredient in an amount of 0.4 g to 0.67 g per 100 kcal of calorie consumed in a daily diet of a blood donor, and inhibits glycation of collagen, A pharmaceutical composition for preventing skin aging for oral intake having any of the formulations selected from the group consisting of powders, syrups, and drinks. The method of claim 11,
A pharmaceutical composition for preventing skin aging, comprising 1.5% by weight to 2.5% by weight of xylitol.

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