JPWO2011061932A1 - Ceramide and collagen synthesis promoter and collagen saccharification inhibitor - Google Patents

Abstract

By promoting the synthesis of ceramide in the skin, it is possible to enhance the barrier function such as the moisture retention function of the skin. An oral preparation that can be safely ingested is provided. The present invention is a ceramide synthesis promoter, collagen synthesis promoter and collagen saccharification inhibitor that orally ingests xylitol, and is excellent in ceramide synthesis promotion effect, collagen amount increase effect and collagen saccharification inhibitory effect, and is safe Can be consumed.

Description

  The present invention relates to ceramide and collagen synthesis promoters and collagen saccharification inhibitors.

  Conventionally, it is known that problems such as dry skin, wrinkles and sagging occur as skin ages and cortex deteriorates.

  Dry skin refers to a condition in which the moisture retention function of the skin is reduced, the skin is dried, and the surface thereof is crisp. Dry skin is susceptible to external stimuli and is prone to rough skin, irritation, rash, eczema, chapped skin, etc., and therefore needs to be improved.

  As a method for preventing dry skin and improving dry skin, a method of applying an external preparation containing ingredients for suppressing moisture evaporation such as petrolatum, mineral oil, ceramide and the like to the skin is performed. As a method for preventing the skin from wrinkling and sagging, a method of applying collagen to the skin has been performed. However, it is technically very difficult to exert the same water retention function as that of the original skin simply by applying such an external preparation. Moreover, the effect is temporary, and it is said that the lasting effect is doubtful, and there is a problem that it cannot be a fundamental solution for dry skin, wrinkles and sagging.

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

  Ceramide is a complex lipid in which a sphingosine base and a fatty acid are bonded with an acid amide, and is a major component of the keratinocyte lipid in the epidermis. While stratum corneum lipids play an important role in maintaining the skin barrier function against water permeation, chemical stimulation, and physical stimulation, ceramide contributes particularly to the barrier function against water permeation. Therefore, the amount of ceramide contained in the skin is an important indicator for measuring the moisture retention function of the skin. A decrease in ceramide is considered to be one of the causes of dry skin seen in atopic dermatitis and xeroderma of the elderly (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 catalyzes the first reaction in the biosynthesis of sphingolipids including ceramide.

On the other hand, collagen, which is one of the extracellular matrix, is a fibrous protein having a helical structure composed of three polypeptide chains as a basic structural unit. The amino acids constituting collagen are mainly composed of glycine, proline, hydroxyproline, alanine, and the like. Among them, hydroxyproline is an amino acid characteristic of collagen, and is therefore used as an index for quantifying the amount of collagen.
Collagen plays an important role in maintaining the elasticity of the skin, and the decrease in the amount of collagen in the skin and the qualitative change in collagen correlate with natural aging due to aging and photoaging due to ultraviolet rays. It is known to cause sagging. Collagen glycation, which is one of the qualitative changes, is a phenomenon that progresses with aging, and has recently been considered as one of the skin aging phenomena.

As ceramide synthesis promoters, nicotinic acid derivatives (patent document 1), plant extracts (patent documents 2 to 4), herbal medicine (non-patent document 2), milk phospholipids (non-patent document 3), sake components (non-patent documents) Patent Literature 4), Niacinamide (Non-Patent Literature 5) and the like are disclosed.
As a collagen synthesis promoter, zymomonas fermentation metabolite (Non-patent Document 10), plant extract (Patent Documents 5 to 9), collagen peptide-like dipeptide or tripeptide (Patent Documents 10 to 11), γ-oryzanol degradation product ( Patent Document 12) and the like are disclosed.
However, some of these are highly irritating to the skin and others are insufficient in terms of safety. In addition, some of the active ingredients are directly applied to cultured cells to evaluate the effect, but when considered for use in humans or animals, the active ingredient is absorbed into the body or the active ingredient is somehow in the body. It is unclear whether the effect can be exerted even after metabolism, and it is not clear whether a sufficient effect can be obtained. In other words, it is difficult to say that the effect and safety are sufficient.

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

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

  Based on the above problems, the present invention can enhance the barrier function such as the moisture retention function of the skin by promoting the ceramide synthesis of the skin, and further increase the amount of skin collagen and suppress the glycation of the collagen. The purpose is to provide a safe oral preparation that prevents wrinkles and sagging.

As a result of intensive studies on the above problems, the present inventors have found that the ingestion of xylitol promotes the synthesis of ceramide and increases the mRNA expression level of serine palmitoyltransferase. The inventors have also found that oral intake of xylitol increases the amount of collagen in the skin and suppresses glycation of collagen. Based on these findings, the present inventors have completed the present invention.
That is, the present invention relates to an orally ingested ceramide and collagen synthesis promoter, and a collagen saccharification inhibitor, which contain xylitol as an active ingredient.

By taking xylitol orally, the amount of ceramide synthesis and the amount of collagen in the skin can be increased, and the level of glycated collagen can be decreased.
In addition, xylitol has been conventionally used as a sweetener such as confectionery, and there is no problem with its safety even if it is taken orally.

The outline of the test schedule in an Example. In Test Example 1, the graph showing the expression level of serine palmitoyltransferase gene (Spt) in a 3-month test group. In Test Example 1, the graph showing the expression level of serine palmitoyl transferase gene (Spt) in a 6-month test group. In Test Example 2, the graph showing the measurement result of the ceramide level in a 3-month test group. In Test Example 2, the graph showing the measurement result of the ceramide level in a 6-month test group. The process drawing of extraction and fractionation in Test Example 3. In Test Example 3, a graph showing the amount of hydroxyproline in a 3-month test group. In Test Example 3, the graph showing the amount of hydroxyproline in a 6-month test group. In Test Example 3, the graph showing the fluorescence intensity per collagen amount in a 3-month test group. In Test Example 3, the graph showing the fluorescence intensity per collagen amount in a 6-month test group.

Xylitol is a sugar alcohol having 5 carbon atoms and is also called xylitol. It is produced by hydrogenation of xylose and is widely used in confectionery such as chewing gum and candy as a sweetener having no cariogenic properties.
Xylitol is one of polyols such as glycerin and propylene glycol, and since it has high water retention ability and can be expected to increase its water retention function when applied to the skin, it may be formulated as a moisturizing component for external preparations. . However, such an effect is an effect that can be expected when applied externally, and even if xylitol is taken orally, it does not reach the skin as it is and cannot exhibit such an effect.
Regarding the effect on the skin when xylitol was orally ingested, the amount of collagen in the skin was examined in an experiment with rats fed with a xylitol diet containing xylitol at relatively high doses of 5.0% and 10.0% by weight. It has been reported to have an effect of increasing glycation of collagen (Non-Patent Document 6, Non-Patent Document 7). However, there was no knowledge about the effect on ceramide synthesis in the skin. Also, regarding the effect on collagen, if humans ingest a large amount of sugar alcohol including xylitol at one time, side effects such as diarrhea are concerned, so whether the same effect can be expected with less xylitol content Evaluation of was desired.

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

The ceramide synthesis promoter, collagen synthesis promoter, and collagen saccharification inhibitor of the present invention preferably have a daily dose of 0.4 g to 1.35 g per 100 kcal of calories taken by the recipient's daily meal. The amount of xylitol is contained as an active ingredient. More preferably, it contains xylitol as an active ingredient in an amount of 0.4 g to 0.67 g per 100 kcal of calories ingested by the daily diet of the recipient. The ceramide synthesis promoter, collagen synthesis promoter and collagen saccharification inhibitor of the present invention preferably contain xylitol as an active ingredient in a proportion of 0.1 wt% to 99 wt%, more preferably 1 It contains in the ratio of weight%-90 weight%.
The ceramide synthesis promoter, collagen synthesis promoter and collagen saccharification inhibitor of the present invention are characterized by being taken orally.

The ceramide synthesis promoter, collagen synthesis promoter, and collagen saccharification inhibitor of the present invention can be used as, for example, pharmaceuticals, quasi drugs or foods and drinks.
In the case of pharmaceuticals, it is administered as an oral agent. Examples of oral dosage forms include tablets, capsules, powders, syrups, and drinks. In the case of quasi drugs, it is used in dosage forms such as tablets, capsules, drinks and the like. In the case of food and drink, in addition to beverages such as drinks, foods such as candy, rice crackers, and cookies, preference items such as tobacco and chewing gum, feeds and feeds, or cosmetics such as mouthwashes and toothpastes, and the like. Note that these are merely examples, and the present invention can be used for any article as long as xylitol can be taken orally.
In the case of a pharmaceutical product or quasi-drug, it may contain one or more pharmacologically acceptable carriers and, if necessary, other active ingredients for treatment. In addition, it contains excipients, binders, disintegrants, lubricants, dispersants, surfactants, plasticizers, suspending agents, emulsifiers, diluents, buffers, antioxidants, bacterial inhibitors, etc. May be.
In addition, the food and drink may contain a substrate, carrier, excipient, additive, extender, colorant, fragrance and the like that are acceptable for food production.
The components other than xylitol are not limited to the above, and the present invention may optionally contain any known components.

  The ceramide synthesis promoter, collagen synthesis promoter and collagen saccharification inhibitor containing xylitol of the present invention can be produced by any method known in the respective technical fields. In the production process, xylitol may be added by any known method.

  The xylitol-containing ceramide synthesis promoter, collagen synthesis promoter and collagen glycation inhibitor of the present invention are used not only for humans but also for animals other than humans (hereinafter abbreviated as non-human animals). be able to. Examples of non-human animals include non-human animals such as mammals, reptiles, amphibians and fish.

  With the above configuration, in the present invention, the same effect of promoting the synthesis of ceramide as that of a conventional ceramide synthesis promoter taken orally can be expected. Therefore, it can be used for the purpose of enhancing the moisture retention function of the skin, improving dry skin, and the like. Further, in the present invention, an effect agent that promotes collagen synthesis and an effect of suppressing glycation of collagen can also be expected. Therefore, it can be used for the purpose of preventing wrinkles and sagging of the skin.

  Hereinafter, the present invention will be described using examples, but these examples do not limit the scope of the present invention.

Test animals, animal breeding
Forty SD rats (male, 11 weeks old, weight at growth place shipping: 350-400 g) were purchased from CLEA Japan and used in the experiment. The animals were raised in a conventional animal breeding room under an environment of room temperature 23 ± 1 ° C., humidity 50 ± 10%, and light / dark cycle 12 hours (light period 8: 00-20: 00). Body weights were measured after 2 weeks of acclimatization, and the rats were divided into four test groups shown in Table 1 so that the average body weight of each group was uniform. Thereafter, the rats were reared for 11 weeks as the test feed administration period. Based on body weight at 11 weeks, the groups were divided into 3 and 7 animals so that the average body weight within each test group was equal. Groups divided into three were reared and dissected for another week (12 weeks, 3 months test group). Groups divided into 7 animals were reared for an additional 13 weeks and dissected (24 weeks, 6 months test group). FIG. 1 shows an outline of the test schedule.

The basic composition of the feed was AIN-93G standard purified feed. A feed (see Table 2) having a composition in which sucrose was replaced with xylitol was prepared and used in the test. During the acclimation breeding, the same feed as the control group was given. In addition, about the calorie of xylitol, since both values of 2.40 kcal / g and 3.00 kcal / g are generally accepted, Table 2 shows the results calculated based on both values.

Feed and water were freely consumed. From one week before dissection, the feeding time was 18:30 from 16:30 to 10:30 the next day, and fasted between 10:30 and 16:30. The body weight measurement and the measurement of the amount of feed and the amount of residual food were performed once every two days, and the difference between the two was used as the amount of food intake. We also observed and recorded the state of feces and the presence or absence of abnormalities such as diarrhea.
Two to three weeks after the test breeding, one animal in the 5% xylitol diet group had a trauma caused by scratching of the back, and healed afterwards, but this animal was excluded from the analysis because it was considered to have an effect on the skin analysis. In addition, at the 10th week of the test breeding, hematuria was observed in one animal in the xylitol 1.5% diet group, and the subsequent body weight was not stable, so this animal was excluded from the analysis.

Results of breeding One to ten rats in the xylitol 5.0% mixed group showed soft stool (tangible stool with high water content) for 1 to 2 days after the start of test feed administration. Recovered. In addition, the changes in the average body weight of rats in each group during the 3-month feeding period, the changes in the total average food intake for one week, and the cumulative food intake for three months There was no significant difference.

Dissection and collection of each sample Dissection was performed by administering the anesthetic agent Somnopentyl (Kyoritsu Pharmaceutical Co., Ltd.) into the peritoneal cavity of 0.1 mL per 100 g body weight. After anesthesia, the hair on the back of the rat was shaved with a clipper, and then a slide glass coated with an instantaneous adhesive (Aron Alpha) was applied to the back surface for 1 minute to collect sebum on the skin surface. Thereafter, back skin (a part of the skin was cut into a circle with a φ = 1.8 cm punch), plasma (blood collected from the heart), liver, and accessory testicular fat were collected.

[Test Example 1] Measurement of expression level of ceramide synthase Extraction of total RNA from skin and preparation of cDNA The collected skin tissue was crushed in a frozen state, and about 350 mg of crushed skin pieces were used as samples. Extraction of total RNA from skin tissue is SV
The total RNA isolation system (Promega) was used. cDNA was prepared from 2 μg of total RNA by reverse transcription (High Capacity cDNA Reverse Transcription Kit, ABI). The prepared cDNA was diluted 5-fold with sterilized water for use in real-time PCR analysis.

Gene expression analysis by real-time PCR
Real-time PCR reaction mixture of 96-well tube (ABI) mixed with serine palmitoyltransferase (Spt) primer and probe, TaqMan (registered trademark) Universal Master Mix II (ABI), and 5 times dilution of the cDNA prepared in the previous section 1 μL of the sample was added, and gene expression analysis was performed by real-time PCR (type 7300, ABI). The primers and probes used the following sequences. Note that FAM was bound to the 5 ′ end of the oligo DNA used for the probe, and TAMRA was bound to the 3 ′ end. The amount of mRNA was determined as a relative value to the control group after correction with the expression level of β-actin, which is a housekeeping gene.
Forward primer: 5′-CAG TGC AGC CTG CTT TGC TA-3 ′ (SEQ ID NO: 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 ′ (SEQ ID NO: 3)

Results of measuring the expression level of serine palmitoyltransferase gene (Spt)
The expression level of the serine palmitoyl transferase gene (Spt) in the 3-month test group is shown in FIG. 2, and the expression level of the serine palmitoyl transferase gene (Spt) in the 6-month test group is shown in FIG.
Although no statistically significant difference or significant trend was observed between the groups, the expression level was higher in the xylitol-administered group than in the control group.

[Test Example 2] Measurement of the amount of skin ceramide Extraction of skin ceramide A sebum sample collected on the slide glass from the back skin surface at the time of dissection was immersed in a solvent mixed with hexane: ethanol 95: 5, and the lipid component was removed by ultrasonication. Extracted. The extracted lipid component was filtered through a hydrophobic filter (Millex (registered trademark) -FH, φ = 0.45 μm, Millipore), transferred to a test tube, and concentrated and dried with nitrogen gas. The dried lipid component was redissolved with chloroform, transferred to a brown microtube, and concentrated and dried again with nitrogen gas. At this time, the weight of the microtube was measured in advance, and the difference from the weight after concentration and drying with nitrogen gas was defined as the total lipid amount.
10 mg of chloroform was added to 1 mg of the obtained total lipid to dissolve the lipid component, and this was used as a total lipid sample to be subjected to the TLC method.

Quantification of skin ceramide content by TLC method Spot 5μL of total lipid sample (equivalent to 0.5mg of total lipid) on silica gel plate (HPTLC, Merck) and develop with developing solvent (chloroform: methanol: acetic acid = 192: 7: 1). I let you. After completion of the development, the silica gel plate was sufficiently dried and then sprayed with a copper (II) sulfate-phosphate solution (coloring reagent) prepared according to the formulation shown in Table 3, and heated at 150 ° C. for about 10 minutes. As a sample, ceramide derived from bovine brain (Ceramide, Natural Mixture, Funakoshi) was used. The spots that appeared on the silica gel plate were digitized with an image analyzer (LAS-3000, Fuji Film).

Measurement result of skin ceramide level
The measurement result of the ceramide level in the 3-month test group is shown in FIG. Although there was no statistically significant difference or trend between the groups, the xylitol-treated group generally showed higher values than the control group, especially the xylitol 2.5% diet group was higher than the control group Met.
The measurement result of the ceramide level in the 6-month test group is shown in FIG. The xylitol 1.5% dietary group and the 5.0% dietary group were statistically significantly increased by 1.4 to 1.5 times compared to the control group. The xylitol 2.5% diet group was also higher than the control group, although no statistically significant difference or trend was observed.

[Test Example 3] Evaluation of skin collagen amount, measurement of glycated collagen amount in collagen Extraction and fractionation of total collagen Extraction and fractionation were performed according to Non-Patent Document 8 (see FIG. 6).
The collected skin was frozen and crushed, degreased and dehydrated with acetone, and cut with a dissecting scissor. Thereafter, the powder was pulverized by 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 the mixture was extracted by shaking at 4 ° C. for 16 hours, followed by centrifugation at 30,000 G and 4 ° C. for 30 minutes to separate the supernatant and the precipitate.
To the supernatant, pepsin 1: 10,000 (for biochemistry, Wako Pure Chemical Industries) was added to a final concentration of 100 mg / mL and reacted at 22 ° C. for 16 hours to decompose non-collagenous proteins. Thereafter, sodium chloride was added so that the final molar concentration was 1.8 M, and centrifugation was again performed at 30,000 G, 10 minutes, 4 ° C., and the resulting precipitate dissolved in 0.1 M acetic acid was used as the acid-soluble fraction. did.
On the other hand, for the precipitate after extraction with 0.5M acetic acid, the precipitate was washed once with the collagenase buffer prepared with the composition shown in Table 4, and then 3 mL of collagenase enzyme solution prepared with the composition shown in Table 5 to a concentration of 200 units / mL. In addition, the reaction was allowed to proceed at 37 ° C. for 22 hours. Thereafter, centrifugation was performed at 30,000 G for 30 minutes at 4 ° C., and the supernatant was used as a collagenase-soluble fraction.

Quantification of hydroxyproline (Hyp) Hydroxyproline was quantified according to Non-Patent Document 8 and Non-Patent Document 9.
500 μL of 6N hydrochloric acid was added to and mixed with 20 μL of the acid-soluble fraction or collagenase-soluble fraction, followed by acid hydrolysis at 130 ° C. for 3 hours. After cooling, 2 μL of 0.04% methyl red solution and 1150 μL of 2.5N sodium hydroxide were added as pH indicators. A dilute aqueous solution of hydrochloric acid and sodium hydroxide was added as appropriate to adjust the pH to 6 to 7 so that the color of the solution was an intermediate color between pink and light yellow.
Thereafter, 1 mL of a 50 mM chloramine T solution prepared with the composition described in Tables 6 and 7 was mixed, reacted at room temperature for 20 minutes, mixed with 1 mL of 18.9% perchloric acid aqueous solution, and reacted at room temperature for 5 minutes. Thereafter, 1 mL of a 20% p-dimethylaminobenzaldehyde solution prepared with the composition shown in Table 8 was mixed and reacted in a 60 ° C. hot water bath for 20 minutes. After cooling with running water for 5 minutes and allowing to stand at room temperature for 1 hour or longer, the absorbance at 557 nm was measured with a spectrophotometer (U-3900H, Hitachi), and the amount of hydroxyproline was determined from a calibration curve. A value obtained by multiplying the amount of hydroxyproline thus obtained by a conversion factor of 7.25 was defined as a collagen conversion value.

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

Measurement result of hydroxyproline amount
FIG. 7 shows the amount of hydroxyproline in the 3-month test group, and FIG. 8 shows the amount of hydroxyproline in the 6-month test group.
In the 3-month test group, neither the acid-soluble fraction nor the collagenase-soluble fraction showed a statistically significant difference or trend between the groups. The amount of proline increased, and particularly in the collagenase-soluble fraction, all the xylitol mixed groups were statistically significantly higher than the control group. Since the amount of hydroxyproline, an amino acid characteristic of collagen, has increased, it is considered that the amount of collagen synthesized has increased in the xylitol mixed diet group.

Measurement result of glycated collagen level
Fig. 9 shows the fluorescence intensity (glycated collagen level) per collagen amount calculated from the hydroxyproline amount in the 3-month test group. Fig. 9 shows the fluorescence intensity (glycated collagen level) per collagen amount calculated from the hydroxyproline amount in the 6-month test group. Each is shown in FIG.
In all fractions, a decrease in glycated collagen level was observed. Particularly in the 3-month test group, the xylitol 2.5% diet group was significantly lower than the control group in the collagenase-soluble fraction. In the 6-month study group, the values of all xylitol mixed groups (1.5%, 2.5%, 5.0%) were significantly lower than the control group in both acid-soluble and collagenase-soluble fractions. It was.

As described above, the ceramide synthesis promoting effect was observed in the xylitol-administered group compared to the control group in which xylitol was not administered. Moreover, even if compared with the patent documents 1-4 which are the results of oral ingestion of components other than xylitol, and the non-patent documents 2-5, it was recognized that it has the same synthesis effect.
In addition, the effect of promoting the synthesis of collagen and the effect of suppressing the glycation of collagen were observed in the kylitol-administered group as compared with the control group.

[Example 4]
Tablets were prepared according to the following formulation.
Xylitol 40%
Crystalline cellulose 25%
Lactose 25%
Corn starch 8%
Magnesium stearate 2%
The above ingredients were mixed uniformly, and the mixed powder was tableted by tableting.

[Example 5]
Tablets were prepared according to the following formulation.
80% xylitol
Lactose 8%
Hydroxypropylcellulose 10%
Magnesium stearate 2%
The above ingredients were mixed uniformly, and the mixed powder was tableted by tableting.

[Example 6]
A syrup was prepared according to the following formulation.
Simple syrup 30%
Xylitol 20%
Purified water 50%

[Example 7]
Capsules were prepared according to the following formulation.
Xylitol 99%
Magnesium stearate 1%
The above ingredients were mixed uniformly and the mixed powder was filled into hard capsules.

[Example 8]
Capsules were prepared according to the following formulation.
90% xylitol
Lactose 8%
Magnesium stearate 2%
The above ingredients were mixed uniformly and the mixed powder was filled into hard capsules.

[Example 9]
A powder was prepared according to the following formulation.
Xylitol 65%
Corn starch 9.9%
Hydroxypropylcellulose 25%
l-Menthol 0.1%

[Example 10]
A drink was prepared according to the following formulation.
Xylitol 5%
Acidulant 1.2%
Fructose glucose liquid sugar 6%
Fragrance 0.1%
Purified water 87.7%

[Example 11]
A drink was prepared according to the following formulation.
Xylitol 1%
Acidulant 1.4%
Fructose dextrose liquid sugar 8%
Fragrance 0.1%
Purified water 89.5%

[Example 12]
A drink was prepared according to the following formulation.
Xylitol 0.1%
Acidulant 1.2%
2% sugar
Fructose dextrose liquid sugar 8%
Fragrance 0.2%
Purified water 88.5%

  This application claims priority from Japanese Patent Application No. 2009-262951 filed on Nov. 18, 2009, the contents of which are incorporated herein by reference.

Claims (9)

  A ceramide synthesis accelerator for oral consumption, characterized by containing xylitol as an active ingredient.   The ceramide synthesis promoter for oral consumption according to claim 1, comprising xylitol in an amount of 0.1 wt% to 99 wt%.   It contains xylitol as an active ingredient in an amount of 0.4 g to 1.35 g per 100 kcal of calories ingested in the daily diet of the recipient, as an active ingredient. Ceramide synthesis promoter for oral intake.   A collagen synthesis promoter for oral consumption, characterized by containing xylitol as an active ingredient.   5. The collagen synthesis promoter for oral consumption according to claim 4, wherein xylitol is contained in an amount of 0.1% to 99% by weight.   5. The xylitol as an active ingredient is contained in an amount of 0.4 g to 1.35 g per 100 kcal of calories ingested in a daily diet of the recipient, as an active ingredient. Collagen synthesis promoter for oral intake.   A collagen saccharification inhibitor for oral consumption characterized by containing xylitol as an active ingredient.   The collagen saccharification inhibitor for oral ingestion according to claim 7, comprising xylitol in an amount of 0.1 wt% to 99 wt%.   8. The xylitol as an active ingredient is contained in an amount of 0.4 g to 1.35 g per 100 kcal of calories ingested in a daily diet of the recipient, as an active ingredient. Collagen saccharification inhibitor for oral intake.

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