JP5154762B2 - Interleukin 6 production inhibitor - Google Patents

Description

  The present invention relates to an interleukin 6 production inhibitor, and more specifically, an interleukin that can be used as an anti-inflammatory agent for prevention or treatment of skin injury by inhibiting production of interleukin 6 associated with skin injury. 6 production inhibitors.

  Cytokines including interleukin 6 are produced from cells in order to maintain tissue homeostasis. However, continuous exposure to ultraviolet rays (sunlight) over a long period of time, continuous stimulation from outside / inside, etc. Causes excessive production of chemical mediators, cytokines, and the like from the epidermal keratinocytes to the skin and damages the skin tissue. In particular, excessive production of interleukin 6 is deeply involved in keratinocyte proliferation, collagen and proteoglycan production from fibroblasts and promotion of collagenase secretion, and skin damage such as skin inflammation and skin thickening is considered to occur. (See Non-Patent Documents 1 to 6).

  Therefore, it can be expected that suppressing excessive production of interleukin 6 is effective for treatment and prevention of skin injuries such as skin inflammation and skin thickening. Therefore, in order to suppress the excessive production of interleukin 6 related to these skin injuries, use of primrose extract, active vitamin D, glucocorticoid and the like has been reported (Patent Document 1 and Non-Patent Documents 7 to 7). 8).

  However, continuous administration of these components has a problem in safety and cannot be used for a long time.

JP 2003-261454 A Oxholm A et al. “Keratinocyte-expression of interleukin-6 but not of tumoure allergic and theirritant patch test reaction”, Acta Derm Venereol., 1991, Vol. 71, P. 93-98. Nishimura N et al. “Defectiveimmune response and severe skin damage following UVB irradiation ininterlerleukin -6-deficience mice”, Immunology, 1999, Vol.97.P77-83 Shinichi S et al. “Serum levels of interleukin-6 and interleukin-10 correlate with total skin thickness scorein patients with systemic sclerosis”, J. of Dermtol. Sci 2001, Vol. 27.P140-146 Matthew R et al. “Stimulation of collagen and glycosaminoglycan production in cultured human adult dermal fibroblasts by recombinant human Interleukin 6”, The j. Invest. Dermatol. 1991, Vol. 97.P686-692 Rachel M. Grossaman et. Al. “Interleukin 6is expressed in high levels in psoriatic skin and stimulates proliferationofcultured human keratinocytes”, Proc. Natl. Acad. Sci. USA, 1989, Vol. 86, P6367-6371 Meinhard Wlaschek et al. “UVA-induced autocrine stimulation of fibroblast-derived-collagenase by IL-6: A possible mechanism in dermalphotodamage?”, J. Invest. Dermatol. 1993, Vol. 101, P164-168 C. Feliciani P et al. “IL-1α, IL-6 and TNF-α in cutaneus lesions of iupus erythematosus are inhibited by topical application of calcipotriol”, Int. J of Immunopathol. Pharmacil. 1995, Vol. 8, P199-207 Lange K et al. “Cutaneous inflammation and proliferation in vitro: differential effects and mode of action of topical glucocorticoids”, Skin Pharmacol Appl Skin Physiol. 2000, Vol. 13, P93-103

  Therefore, the present invention finds a highly safe substance that suppresses interleukin 6 production that can be blended into a skin external preparation and can be used for a long period of time, and provides an interleukin 6 production inhibitor using the substance. It is to be an issue.

  As a result of intensive studies to solve the above problems, the present inventors have found that an oligosaccharide obtained by degrading agarose has an excellent interleukin 6 production inhibitory action, and has led to the completion of the present invention. It was.

  That is, the present invention is an interleukin 6 production inhibitor containing, as an active ingredient, at least one saccharide selected from the group consisting of neoagarobiose, neoagarotetraose and neoagarohexaose.

  The interleukin 6 production inhibitor of the present invention can effectively inhibit the production of interleukin 6 involved in the proliferation of keratinocytes, the production of collagen from fibroblasts, the production of proteoglycan and the secretion of collagenase, etc. It can be used as an anti-inflammatory agent having an effect of treating or preventing skin injury such as skin thickening.

  Moreover, since it has the effect | action which acts on the melanocyte in skin cells and inhibits the melanocyte stimulating hormone ((alpha) -MSH) which accelerates | stimulates melanin production, it has a whitening effect.

  Therefore, the interleukin 6 production inhibitor of the present invention can be advantageously used as a skin external preparation for cosmetics, pharmaceuticals, quasi drugs and the like.

  The interleukin 6 production inhibitor of the present invention contains at least one saccharide selected from the group consisting of neoagarobiose, neoagarotetraose and neoagarohexaose as an active ingredient.

  Neoagarobiose, neoagarotetraose and neoagarohexaose used in the present invention are oligosaccharides (neoagarooligosaccharides) obtained by decomposing agarose (purified agar) with β-agarase.

  Among these neoagaro-oligosaccharides, neoagarobiose is a disaccharide in which 3,6-anhydro-L-galactose and D-galactose are linked by α-1,3, and includes neoagarotetraose (tetrasaccharide) and neo Agalohexaose (hexasaccharide) also has the same structural unit.

  The method for producing neoagarobiose, neoagarotetraose and neoagarohexaose (hereinafter sometimes referred to as “neoagarooligosaccharide”) used in the present invention is not particularly limited. It can be produced using β-agarase purified by the method described in JP-A-1-228465. More specifically, for example, agar or agarose is added to a 10 mM Tris-HCl buffer solution (pH 7.5) or purified water so as to have a concentration of 1.0% and dissolved by heating. Add to a concentration of ml or more and allow to act at 50 ° C. for 4 hours or more. The reaction is stopped by leaving the solution in boiling water for 5 minutes and cooled to 4 ° C.

  Here, in particular, when agar is used as a substrate, insoluble precipitates and the like are present, so that the residue is removed by centrifugation. Since the resulting supernatant contains neoagaro-oligosaccharides, a mixture of neo-agaro-oligosaccharides can be obtained by lyophilization. The supernatant may be separated and purified by a known method to obtain a purified product of each sugar alone.

  The content of the neoagalo-oligosaccharide thus obtained is not particularly limited, but is 0.0001 to 2% by mass (hereinafter referred to as “%”) with respect to the total amount of interleukin 6 production inhibitor, Furthermore, it is preferable to set it as 0.01 to 0.5%. Moreover, although the composition ratio is not particularly limited, for example, a range of neoagarobiose: neoagarotetraose: neoagarohexaose = 5: 50: 45 to 20:40:40 is preferable.

  In the production of the interleukin 6 production inhibitor of the present invention, it is usually used in the production of at least one of the above-mentioned neoagaro-oligosaccharides which are active ingredients and pharmaceuticals, quasi-drugs, cosmetics and the like. Arbitrary components can be appropriately blended to prepare an external preparation or an oral preparation.

  Examples of such optional components include purified water, pH adjusters, lower alcohols, polyhydric alcohols, oils, powders, surfactants, water-soluble polymers, preservatives, fragrances, buffers, dyes, and UV absorption. Agents, various medicinal components and the like can be exemplified.

  The interleukin 6 production inhibitor of the present invention thus obtained can be various forms of cosmetics, pharmaceuticals, quasi drugs, etc., and in a conventional manner, a facial cleanser or cleanser, lotion, emulsion, It can be in the form of cosmetic external preparations such as creams, packs, massages, bases, foundations, hair nourishing / hair growth agents, and medical external preparations such as ointments, creams and poultices.

  As described above, excessive production of interleukin 6 is deeply involved in keratinocyte proliferation, collagen and proteoglycan production from fibroblasts and promotion of collagenase secretion, and skin damage such as skin inflammation and skin thickening occurs. Since it is considered, the interleukin 6 production inhibitor of the present invention can be used as an anti-inflammatory agent for treating or preventing such skin injury.

  Furthermore, since the interleukin 6 production inhibitor of the present invention has an action of inhibiting α-MSH that acts on melanocytes in skin cells and promotes melanin production, it also has an excellent whitening action.

  EXAMPLES Next, although an Example is given and this invention is demonstrated in more detail, this invention is not restrict | limited at all by these Examples.

Manufacturing example 1
Production of neoagaro-oligosaccharide Agarose is added to purified water to a concentration of 1.0%, and β-agarase purified by the method described in JP-A-1-228465 is added thereto to a concentration of 50 mU / ml. And allowed to act at 50 ° C. for 4 hours or longer. The reaction was stopped by leaving this solution in boiling water for 5 minutes and cooled to 4 ° C. The obtained supernatant was freeze-dried to obtain neoagaro-oligosaccharide. This neoagaro-oligosaccharide was composed of 8% neoagarobiose, 53% neoagarotetraose, and 39% neoagarohexaose.

Test example 1
Inhibition of interleukin 6 production during UV irradiation in keratinocytes Human normal skin keratinocytes (Kurabo) were cultured using KGM2 medium (Kurabo), and this was cultured in a 24-well plate at 1 × 10 ⁴ / cm ² . Seeded at density and cultured to sub-confluent state. A neo-agaro-oligosaccharide 5% solution (a mixture of neo-agarobiose 8%, neo-agarotetraose 53%, neo-agarohexaose 39%; manufactured by Ina Food Industry Co., Ltd.) is added to the cultured cells. Was added to 0, 0.0167, 0.05, 0.167, and 0.5%. Three hours later, after washing twice with PBS, Hank's solution was added twice and irradiated with 50 mJ of ultraviolet light (UV-B). After removing the Hanks solution, the medium was added and the sample was added again. After 24 hours, the medium was collected. The collected medium was subjected to centrifugal filtration to remove cell components and the like. The separated medium was measured using a measurement kit (Interleukin-6 [(h) IL-6] Human, ELISA; Biotrak System.
). In addition, it measured similarly about the cell which is not irradiated with an ultraviolet-ray. The results are shown in FIG. From FIG. 1, it became clear that neoagaro-oligosaccharide suppresses the production of interleukin 6 by UV irradiation, and the effect was more remarkable as the concentration was higher.

Test example 2
Melanin production suppression test using cultured cells (α-MSH inhibition)
B16 melanoma cells derived from mice were used as cultured cells, and a melanin production inhibition test was conducted. A 10% FBS-containing MEM medium was added to a petri dish with a diameter of 100 mm, seeded with mouse-derived B16 melanoma cells, and cultured at 37 ° C. in a carbon dioxide concentration of 5%. The following day, neo agaro-oligosaccharide 5% liquid (neo agarobiose 8%, neo agaro tetraose 53%, neo agaro hexaose 39% mixture; manufactured by Ina Food Industry Co., Ltd.) to various concentrations, The final concentration of neoagaro-oligosaccharide is 0, 0.005, 0.015, 0.05% added to the medium, and 30 minutes later, α-MSH is adjusted to a final concentration of 1 × 10 ⁻⁷ M. Added and mixed. On the 5th day of the culture, the medium was changed, and the neoagalo-oligosaccharide solution having the same concentration and amount was added again. On the next day, the cells were collected and aligned to a certain number of cells, and then the amount of melanin in the cells was quantified. The amount of melanin produced was shown with the amount of melanin produced as a control, with α-MSH added and no neoagaro-oligosaccharide added as a control. In addition, the amount of melanin produced was similarly determined for cells to which α-MSH was not added. The results are shown in FIG. FIG. 2 reveals that neoagalo-oligosaccharides remarkably suppress the production of melanin by the addition of α-MSH, indicating that neo-agaro-oligosaccharide has an α-MSH inhibitory action.

Example 1
Cleansing cream A cleansing cream having the following composition was prepared by the following method.
(Composition) (%)
(1) Stearic acid 2.0
(2) Stearyl alcohol 3.0
(3) Lipophilic glyceryl monostearate 2.0
(4) Beeswax 1.5
(5) Vaseline 6.0
(6) Liquid paraffin 40.0
(7) Dimethylpolysiloxane (100CS) 0.5
(8) Sorbitan sesquioleate 1.0
(9) Preservative appropriate amount (10) Triethanolamine 1.0
(11) Propylene glycol 10.0
(12) Polyethylene glycol 20000 0.5
(13) Carboxyvinyl polymer 0.05
(14) Residual amount of purified water (15) Neoagaro-oligosaccharide solution * 1 1.0
(16) Fragrance appropriate amount * 1: 5% solution of neoagalo-oligosaccharide produced in Production Example 1 (Production method)
A. Ingredients (1) to (9) are dissolved by heating and maintained at 70 ° C.
B. Ingredients (10) to (14) are dissolved by heating and maintained at 70 ° C.
C. A is added to B and emulsified.
D. After cooling C, components (15) and (16) were added and mixed to obtain a cleansing cream.

  This cleansing cream had a light spread and good makeup removal, smoothed skin irritation and thickening, and smoothed the skin.

Example 2
The cleanser wash face charges following composition was prepared in the preparation below.
(Composition) (%)
(1) Lauric acid 5.0
(2) Myristic acid 18.5
(3) Stearic acid 6.0
(4) Glycerin 12.0
(5) Polyethylene glycol 1500 5.0
(6) Potassium hydroxide 6.5
(7) Purified water remaining amount (8) Palm oil fatty acid diethanolamide 5.0
(9) Palm oil fatty acid methyl taurine sodium 1.8
(10) Polyoxyethylene (7.5E.O.) 2.0
Lauryl ether (11) ethylene glycol distearate 1.0
(12) Hydroxypropyl methylcellulose 1% aqueous solution 5.0
(13) Neoagaro-oligosaccharide solution * 1 2.0
(14) Appropriate perfume (production method)
A. Components (1) to (7) are dissolved by heating.
B. Components (8) to (11) are dissolved by heating.
C. Add B to A and mix.
D. After cooling C, components (12) to (14) were added and mixed to obtain a face wash.

  This facial cleanser has a fine and rich foaming and a refreshing feeling of use, and it suppresses inflammation and thickening of the skin and smoothes the skin.

Example 3
Lotion 1 (dissolving type)
A lotion having the following composition was prepared by the following production method.
(Composition) (%)
(1) Citric acid 0.05
(2) Sodium citrate 0.2
(3) Sodium pyrrolidonecarboxylate (50%) solution 0.5
(4) Glycerin 3.0
(5) 1,3-butylene glycol 8.0
(6) L-ascorbic acid 2-glucoside * 2 2.0
(7) Sodium hydroxide 0.25
(8) Neoagaro-oligosaccharide solution * 1 5.0
(9) Purified water remaining amount (10) Ethyl alcohol 10.0
(11) Perfume appropriate amount (12) Preservative appropriate amount (13) Polyoxyethylene monooleate (20E.O.) 0.5
Sorbitan * 2: Hayashibara Biochemical Research Institute (manufacturing method)
A. Components (1) to (9) are mixed and dissolved.
B. Components (10) to (13) are mixed and dissolved.
C. B was added to A and mixed to obtain a skin lotion.

  This skin lotion has a fresh and refreshing feeling of use, suppresses skin inflammation and skin thickening, keeps the skin fresh and smoothes the skin.

Example 4
Lotion 2 (oil solubilized type)
A lotion having the following composition was prepared by the following production method.
(Production method) (%)
(1) Meadow home oil 0.1
(2) Jojoba oil 0.05
(3) Perfume appropriate amount (4) Preservative appropriate amount (5) Polyoxyethylene monooleate (20E.O.) 0.5
Sorbitan (6) Polyoxyethylene cure of isostearate 1.0
Castor oil (50 EO)
(7) Ethyl alcohol 8.0
(8) Glycerin 5.0
(9) 1,3-butylene glycol 5.0
(10) Polyethylene glycol 1500 0.1
(11) Neoagaro-oligosaccharide solution * 1 1.0
(12) Remaining amount of purified water (production method)
A. Components (1) to (7) are mixed and dissolved.
B. Components (8) to (12) are mixed and dissolved.
C. A was added to B and mixed to obtain a skin lotion.

  This skin lotion has a fresh and mellow feeling of use, suppresses skin inflammation and skin thickening, keeps the skin fresh and smoothes the skin.

Example 5
Lotion 3 (emulsification type)
A lotion having the following composition was prepared by the following production method.
(Composition) (%)
(1) Glyceryl tri-2-ethylhexanoate 0.08
(2) Squalane 0.02
(3) Sorbitan sesquioleate 0.05
(4) Polyoxyethylene monooleate (20E.O.) 0.05
Sorbitan (5) Polyoxyethylene (8EO) alkylene 0.1
(12-15) Ether phosphoric acid (6) Preservative appropriate amount (7) Perfume appropriate amount (8) Ethyl alcohol 8.0
(9) Dipropylene glycol 8.0
(10) Glycerin 4.0
(11) Neoagaro-oligosaccharide solution * 1 1.0
(12) Remaining amount of purified water (production method)
A. Components (1) to (7) are mixed and dissolved.
B. Components (8) to (12) are mixed and dissolved.
C. A was added to B and emulsified to obtain a skin lotion.

  This skin lotion has a clean and light feeling of use, suppresses skin inflammation and skin thickening, keeps the skin fresh and smoothes the skin.

Example 6
The emulsion of the milk solution following composition was prepared in the preparation below.
(Composition) (%)
(1) Stearic acid 1.0
(2) Cetanol 0.5
(3) Lipophilic glyceryl monostearate 0.5
(4) Liquid paraffin 2.0
(5) Squalane 3.0
(6) Jojoba oil 3.0
(7) Cetyl palmitate 3.0
(8) Preservative appropriate amount (9) Sorbitan monostearate 0.3
(10) Polyoxyethylene monooleate (20E.O.) 0.5
Sorbitan (11) Triethanolamine 0.5
(12) 1,3-butylene glycol 15.0
(13) Glycerin 3.0
(14) Polyethylene glycol 6000 0.5
(15) Purified water remaining amount (16) Carboxyvinyl polymer 1% solution 8.0
(17) Dipotassium glycyrrhizinate * 3 0.1
(18) Neoagaro-oligosaccharide solution * 1 1.0
(19) Fragrance appropriate amount * 3: Made by Maruzen Pharmaceutical Co., Ltd. (method)
A. Ingredients (1) to (12) are dissolved by heating and maintained at 70 ° C.
B. Ingredients (13) to (15) are dissolved by heating and maintained at 70 ° C.
C. B is added to A to emulsify, and components (16) to (18) are further added and mixed.
D. C was cooled, and component (19) was added and mixed to obtain an emulsion.

  This emulsion has a smooth and mellow feeling, suppresses skin inflammation and skin thickening, gives the skin a moisturizing feeling and an appropriate emollient feeling, and softens the skin.

Example 7
Cream A cream having the following composition was prepared by the following production method.
(Composition) (%)
(1) Stearic acid 2.5
(2) Cetanol 2.5
(3) Lipophilic glyceryl monostearate 2.0
(4) Vaseline 2.0
(5) Dipentaerythritol fatty acid ester * 4 2.0
(6) Isotridecyl myristate 5.0
(7) Liquid paraffin 8.0
(8) Squalane 5.0
(9) Beeswax 1.0
(10) Cetyl palmitate 2.0
(11) Sorbitan sesquioleate 0.5
(12) Polyoxyethylene monooleate (20E.O.) 1.5
Sorbitan (13) Preservative Appropriate amount (14) Triethanolamine 1.2
(15) 1,3-butylene glycol 8.0
(16) Glycerin 2.0
(17) Polyethylene glycol 20000 0.5
(18) Purified water remaining amount (19) 1% aqueous solution of carboxyvinyl polymer 10.0
(20) Arbutin * 5 3.0
(21) Neoagaro-oligosaccharide solution * 1 0.5
(22) Fragrance appropriate amount * 4: Cosmol 168AR (Nisshin Oillio Group)
* 5: Wako Pure Chemical Industries, Ltd. (production method)
A. Ingredients (1) to (13) are dissolved by heating and maintained at 70 ° C.
B. Ingredients (14) to (18) are dissolved by heating and maintained at 70 ° C.
C. B is added to A to emulsify, and component (19) is further added and mixed.
D. C was cooled, components (20), (21) and (22) were added and mixed to obtain a cream.

  This cream had a smooth and rich feeling of use, and it was a cream that suppressed skin irritation and skin thickening, imparted a high emollient feeling to the skin, and softened the skin.

Example 8
Cosmetic liquid (solubilized type)
A serum having the following composition was prepared by the following production method.
(Composition) (%)
(1) Glyceryl tri-2-ethylhexanoate 0.1
(2) Meadow Home Oil 0.05
(3) Jojoba oil 0.05
(4) Preservative appropriate amount (5) Perfume appropriate amount (6) Polyoxyethylene monooleate (20E.O.) 0.5
Sorbitan (7) Cured with polyoxyethylene isostearate 1.5
Castor oil (50 EO)
(8) Ethyl alcohol 5.0
(9) Glycerin 4.0
(10) Dipropylene glycol 8.0
(11) 1,3-butylene glycol 8.0
(12) Sodium lactate 0.5
(13) Sodium pyrrolidonecarboxylate (50%) solution 0.5
(14) Hydroxyethyl cellulose 0.08
(15) Sodium alginate 0.05
(16) Neoagaro-oligosaccharide solution * 1 10.0
(17) Residual amount of purified water (production method)
A. Components (1) to (8) are mixed and dissolved.
B. Components (9) to (17) are mixed and dissolved.
C. A was added to B and mixed to obtain a serum.

  This essence has a mellow and mild feeling of use, suppresses skin inflammation and skin thickening, gives the skin a high moisturizing and emollient feeling, and makes the skin fresh and soft.

Example 9
Pack (Peel-off type)
A pack having the following composition was prepared by the following production method.
(Composition) (%)
(1) Polyvinyl alcohol 12.0
(2) Methylcellulose 0.1
(3) Glycerin 3.0
(4) 1,3-butylene glycol 5.0
(5) Purified water remaining amount (6) Perfume appropriate amount (7) Preservative appropriate amount (8) Glyceryl tri-2-ethylhexanoate 0.1
(9) Polyoxyethylene monooleate (20E.O.) 1.0
Sorbitan (10) ethyl alcohol 13.0
(11) Neoagaro-oligosaccharide solution * 1 1.0
(Production method)
A. Components (1) to (5) are dissolved by heating.
B. Components (6) to (10) are mixed and dissolved.
C. After cooling A, B and component (11) were added and mixed to obtain a pack.

  This pack had moderate refreshment and high tension, suppressed skin irritation and skin thickening, imparted moderate elasticity to the skin after packing, and made the skin soft.

Example 10
Massage cream A massage cream having the following composition was prepared by the following method.
(Composition) (%)
(1) Stearic acid 2.0
(2) Stearyl alcohol 2.5
(3) Lipophilic glyceryl monostearate 2.0
(4) Sorbitan sesquioleate 1.0
(5) Cetyl palmitate 1.0
(6) Dipentaerythritol fatty acid ester * 4 4.0
(7) Vaseline 20.0
(8) Liquid paraffin 28.0
(9) Dimethylpolysiloxane (100CS) 0.5
(10) Sodium hydroxide 0.1
(11) Dipropylene glycol 7.0
(12) Carboxyvinyl polymer 0.1
(13) Remaining amount of purified water (14) Neoagaro-oligosaccharide solution * 1 1.0
(15) Appropriate perfume (production method)
A. Ingredients (1) to (9) are dissolved by heating and maintained at 70 ° C.
B. Components (10) to (13) are dissolved by heating and maintained at 70 ° C.
C. A is added to B and emulsified.
D. After cooling C, components (14) and (15) were added and mixed to obtain a massage cream.

  This massage cream is a massage cream that has a smooth and smooth feeling of use and a high massage effect, suppresses inflammation and thickening of the skin, gives the skin a moisturizing and sticking feeling, and smoothes the skin.

Example 11
Liquid foundation A liquid foundation having the following composition was prepared by the following method.
(Composition) (%)
(1) Stearic acid 2.0
(2) Cetanol 0.5
(3) Behenyl alcohol 1.0
(4) Petrolatum 2.5
(5) Liquid paraffin 5.0
(6) Self-emulsifying glyceryl monostearate 1.0
(7) Preservative appropriate amount (8) Titanium oxide 6.0
(9) Color pigment 4.0
(10) Mica 2.0
(11) Talc 4.0
(12) Carboxymethylcellulose 0.2
(13) Bentonite 0.4
(14) Residual amount of purified water (15) Neoagaro-oligosaccharide solution * 1 1.0
(16) Appropriate perfume (production method)
A. Components (1) to (7) are dissolved by heating.
B. Ingredients (8) to (11) are added to A, mixed uniformly, and kept at 70 ° C.
C. Ingredients (12) to (14) are dissolved by heating and maintained at 70 ° C.
D. B is added to C and emulsified.
E. After cooling D, components (15) and (16) were added and mixed to obtain a liquid foundation.

  This liquid foundation is a liquid foundation that has a light and wide feeling of use, suppresses skin inflammation and skin thickening, and has a uniform and beautiful finish.

  The interleukin 6 production inhibitor comprising the neo-agaro-oligosaccharide of the present invention as an active ingredient can effectively inhibit the production of interleukin 6, and further uses an agar-derived ingredient as an active ingredient. It is possible. Furthermore, this thing also has the outstanding whitening effect | action by inhibiting (alpha) -MSH.

  Therefore, this is extremely useful as an external preparation for skin such as cosmetics and pharmaceuticals.

It is a figure which shows the interleukin 6 production inhibitory effect by neoagaro-oligosaccharide. It is a figure which shows the alpha-MSH inhibitory effect by neoagaro-oligosaccharide.

Claims (5)

Neoagarobiose external skin preparation for preventing inflammation of the skin, including the interleukin-6 production inhibitor containing neo agarotetraose and neo A Gallo hexa O scan as an active ingredient.   The skin external preparation according to claim 1, wherein the skin inflammation is caused by ultraviolet irradiation. Neoagarobiose external skin preparation for preventing or treating skin thickening including interleukin 6 production inhibitor containing neo agarotetraose and neo A Gallo hexa O scan as an active ingredient.   The skin external preparation according to claim 3, wherein the thickening of the skin is caused by ultraviolet irradiation. Neoagarobiose in the skin external preparation, external skin preparation according to one of claims 1 to 4 the content of neo agarotetraose and neo A Gallo hexa O scan is 0.0001 wt%.

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