US 20070135374A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2007/01353.74 A1 Shinohara et al. (43) Pub. Date: Jun. 14, 2007
(54) COMPOSITION FOR PROMOTING Publication Classification COLLAGEN PRODUCTION (51) Int. Cl. (75) Inventors: Shigeo Shinohara, Kyoto (JP); A61K 3 1/7076 (2006.01) Mitsuaki Kawamura, Kyoto (JP) A61K 31/7072 (2006.01) Correspondence Address: (52) U.S. Cl...... 514/46; 514/49 FINNEGAN, HENDERSON, FARABOW, GARRETT & DUNNER LLP (57) ABSTRACT 901 NEW YORK AVENUE, NW WASHINGTON, DC 20001-4413 (US) The invention provides a composition for promoting col (73) Assignee: OTSUKA PHARMACEUTICAL CO., lagen production, and more specifically, provides a compo LTD., Tokyo (JP) sition capable of promoting collagen production in human dermis. Further, the invention provides a method for pro (21) Appl. No.: 10/574,696 moting collagen production. The invention provides a com position for promoting collagen production containing a (22) PCT Filed: Oct. 8, 2004 purine nucleic acid-related Substance as an active ingredient (86). PCT No.: PCT/UP04/15298 as well as a composition for promoting collagen production containing a purine nucleic acid-related Substance and a S 371(c)(1), pyrimidine nucleic acid-related substance. The method for (2), (4) Date: Dec. 4, 2006 promoting collagen production of the invention comprises (30) Foreign Application Priority Data applying a purine nucleic acid-related Substance alone or in combination with a pyrimidine nucleic acid-related Sub Oct. 8, 2003 (JP)...... 2003-34.9156 stance to the skin. Patent Application Publication Jun. 14, 2007 US 2007/0135374A1
Fig. 1
160
40
AMP concentrations of culture media (wiv%)
Fig. 2
Josuo?qerqueou:00AOI?I (Tuyêu)squeqeuaednsaunq?no
Test medium 1 Test medium 2 Test medium 3 Test medium 4 US 2007/01353.74 A1 Jun. 14, 2007
COMPOSITION FOR PROMOTING COLLAGEN 0010 Item 4. A composition for promoting collagen PRODUCTION production according to Item 1, wherein the purine nucleic acid-related Substance is at least one member TECHNICAL FIELD selected from the group consisting of adenosine mono phosphate and a salt thereof. 0001. The present invention relates to a composition for promoting collagen production. The invention also relates to 0011. Item 5. A composition for promoting collagen a method for promoting collagen production in the dermis. production according to Item 1, wherein the purine nucleic acid-related Substance is at least one member selected from the group consisting of adenosine 5'-mono BACKGROUND OF THE INVENTION phosphate and a salt thereof. 0002 About 90% of the dermis of the skin is collagen, 0012 Item 6. A composition for promoting collagen which exhibits the functions of supporting the skin structure, production according to Item 2, wherein the pyrimidine providing an environment for cell Survival, and retaining nucleic acid-related Substance is at least one member moisture. It is known that collagen is lost when the skin is Subject to specific exogenous influences. Such as ultraviolet selected from the group consisting of uracil, uridine, ray exposure, dryness, etc. It has been found that collagen is uridine phosphate, and a salt thereof. lost by aging and stress. It has also been found that Such 0013 Item 7. A composition for promoting collagen exogenous influences and/or aging causes a reduction in the production according to Item 2, wherein the pyrimidine amount of collagen production in skin fibroblast. nucleic acid-related Substance is at least one member selected from the group consisting of uridine monophos 0003. The functions of retaining a moderate amount of phate and a salt thereof. collagen as well as exhibiting an excellent collagen produc tion ability are important in maintaining healthy skin. Here 0014) Item 8. A composition for promoting collagen tofore, Substances that promote collagen production have production according to Item 2, wherein the pyrimidine been actively sought (e.g., Japanese Unexamined Patent nucleic acid-related Substance is at least one member Publication Nos. 2001-316240 and 2003-278783.A). How selected from the group consisting of uridine 5'-mono ever, it has not been reported that nucleic acid and its related phosphate and a salt thereof. Substances have an action of promoting collagen production. 0015 Item 9. A composition for promoting collagen production according to Item 2, wherein the purine SUMMARY OF THE INVENTION nucleic acid-related Substance is at least one member selected from the group consisting of adenine, adenosine, 0004 The invention aims to provide a composition for adenosine phosphate, a metabolite of adenosine phos promoting collagen production, and more specifically, to phate, and a salt thereof and the pyrimidine nucleic provide a composition capable of promoting collagen pro acid-related Substance is at least one member selected duction in human dermis. Further, the invention aims to from the group consisting of uracil, uridine, uridine apply the above-described composition for promoting col phosphate, and a salt thereof. lagen production to external preparations. 0016. Item 10. A composition for promoting collagen 0005 The present inventors carried out extensive production according to Item 2, wherein the purine research to achieve the above-described objects, and found nucleic acid-related Substance is selected from the group that purine nucleic acid-related Substances, especially consisting of adenosine monophosphate and a salt thereof adenosine 5'-monophosphate, and salts thereof, have an and the pyrimidine nucleic acid-related Substance is at action of promoting collagen production in the dermis. least one member selected from the group consisting of Moreover, the inventors found that a pyrimidine nucleic uridine monophosphate and a salt thereof. acid-related Substance has an effect of potentiating the 0017. Item 11. A composition for promoting collagen collagen production promoting action of the purine nucleic production according to Item 2, wherein the purine acid-related Substance. nucleic acid-related Substance is selected from the group 0006 More specifically, the present invention relates to consisting of adenosine 5'-monophosphate and a salt the following compositions for promoting collagen produc thereof and the pyrimidine nucleic acid-related substance tion. is at least one member selected from the group consisting of uridine 5'-monophosphate and a salt thereof. 0007. Item 1. A compositionp for ppromoting 9. collagen9. 0018) Item 12. A composition for promoting collagen production, comprising a purine nucleic acid-related Sub production according to Item 2, wherein the composition Stance. contains the pyrimidine nucleic acid-related Substance in 0008. Item 2. A compositionp for ppromoting 9. collagen9. a proportion of 0.001 to 100 parts by weight per part by production according to Item 1, further comprising a weight of the purine nucleic acid-related Substance. pyrimidine nucleic acid-related Substance. 0019. Item 13. A composition for promoting collagen 0009. Item 3. A composition for promoting collagen production according to Item 1, wherein the composition production according to Item 1, wherein the purine contains the purine nucleic acid-related Substance in a nucleic acid-related Substance is at least one member proportion of 0.01 to 10% by weight based on the total Selected from the group consisting of adenine, adenosine, amount of the composition. adenosine phosphate, a metabolite of adenosine phos 0020 Item 14. A composition for promoting collagen phate, and a salt thereof. production according to Item 1, wherein the composition US 2007/01353.74 A1 Jun. 14, 2007
contains the pyrimidine nucleic acid-related Substance in 0034) Item 27. A method for promoting collagen produc a proportion of 0.0001 to 10% by weight based on the tion according to Item 18, wherein the purine nucleic total amount of the composition. acid-related Substance is at least one member selected from the group consisting of adenine, adenosine, adenos 0021. Item 15. A composition for promoting collagen ine phosphate, a metabolite of adenosine phosphate, and production according to Item 1 used for a cosmetic, or an a salt thereof and the pyrimidine nucleic acid-related externally-applied medical or quasi-medical drug. Substance is at least one member selected from the group 0022. Item 16. A composition for promoting collagen consisting of uracil, uridine, uridine phosphate, and a salt production according to Item 1 used for a cosmetic. thereof. 0023 The invention also relates to the following methods 0035) Item 28. A method for promoting collagen produc for promoting collagen production. tion according to Item 18, wherein the purine nucleic acid-related Substance is selected from the group consist 0024. Item 17. A method for promoting collagen produc ing of adenosine monophosphate and a salt thereof and tion, comprising applying to the skin a purine nucleic the pyrimidine nucleic acid-related Substance is at least acid-related Substance. one member selected from the group consisting of uridine 0.025 Item 18. A method for promoting collagen produc monophosphate and a salt thereof. tion according to Item 17, comprising applying to the skin 0036) Item 29. A method for promoting collagen produc a purine nucleic acid-related Substance in combination tion according to Item 18, wherein the purine nucleic with a pyrimidine nucleic acid-related Substance. acid-related Substance is selected from the group consist ing of adenosine 5'-monophosphate and a salt thereof and 0026. Item 19. A method for promoting collagen produc the pyrimidine nucleic acid-related Substance is at least tion according to Item 17, comprising applying to the skin one member selected from the group consisting of uridine an externally-applied composition containing the purine 5'-monophosphate and a salt thereof. nucleic acid-related Substance. 0037 Item 30. A method for promoting collagen produc 0027. Item 20. A method for promoting collagen produc tion according to Item 18, wherein the composition con tion according to Item 18, comprising applying to the skin tains the pyrimidine nucleic acid-related Substance in a an externally-applied composition containing the purine proportion of 0.001 to 100 parts by weight per part by nucleic acid-related substance and the pyrimidine nucleic weight of the purine nucleic acid-related substance. acid-related Substance. 0038. Item 31. A method for promoting collagen produc 0028) Item 21. A method for promoting collagen produc tion according to Item 19, wherein the externally-applied tion according to Item 17, wherein the purine nucleic composition contains the purine nucleic acid-related Sub acid-related Substance is at least one member selected stance in a proportion of 0.01 to 10% by weight based on from the group consisting of adenine, adenosine, adenos the total amount of the composition. ine phosphate, a metabolite of adenosine phosphate, and a salt thereof. 0039. Item 32. A method for promoting collagen produc tion according to Item 20, wherein the externally-applied 0029) Item 22. A method for promoting collagen produc composition contains the pyrimidine nucleic acid-related tion according to Item 17, wherein the purine nucleic substance in a proportion of 0.0001 to 10% by weight acid-related Substance is at least one member selected based on the total amount of the composition. from the group consisting of adenosine monophosphate and a salt thereof. 0040 Item 33. A method for promoting collagen produc tion according to Item 19, wherein the externally-applied 0030) Item 23. A method for promoting collagen produc composition is used for a cosmetic, or an externally tion according to Item 17, wherein the purine nucleic applied medical or quasi-medical drug. acid-related Substance is selected from the group consist ing of adenosine 5'-monophosphate and a salt thereof. 0041) Item 34. A method for promoting collagen produc tion according to Item 19, wherein the externally-applied 0.031) Item 24. A method for promoting collagen produc composition is used for a cosmetic. tion according to Item 18, wherein the pyrimidine nucleic 0042. Item 35. A method for promoting collagen produc acid-related Substance is at least one member selected tion according to Item 17, comprising applying to the skin from the group consisting of uracil, uridine, uridine the composition for promoting collagen production of phosphate, and a salt thereof. Item 1. 0032) Item 25. A method for promoting collagen produc 0043 Item 36. A method for promoting collagen produc tion according to Item 18, wherein the pyrimidine nucleic tion according to Item 18, comprising applying to the skin acid-related Substance is at least one member selected the composition for promoting collagen production of from the group consisting of uridine monophosphate and Item 2. a salt thereof. 0044) Further, the invention also relates to uses of the 0033 Item 26. A method for promoting collagen produc following aspects. tion according to Item 18, wherein the pyrimidine nucleic acid-related Substance is at least one member selected 0045. Item 37. Use of a purine nucleic acid-related sub from the group consisting of uridine 5'-monophosphate stance for preparation of a composition for promoting and a salt thereof. collagen production. US 2007/01353.74 A1 Jun. 14, 2007
0046) Item 38. Use of a purine nucleic acid-related sub 0054 Examples of such salts include alkali metal salts, stance and a pyrimidine nucleic acid-related Substance for Such as Sodium salts, potassium salts, etc.; alkaline earth preparation of a composition for promoting collagen metal salts. Such as calcium salts, magnesium salts, barium production. salts, etc.; basic amino acid salts, such as arginine, lysine, 0047. Item 39. Use of a purine nucleic acid-related sub etc.; ammonium salts, such as ammonium salts, tricyclo stance for collagen production. hexylammonium salts, etc.; various kinds of alkanolamine salts, such as monoethanolamine salts, diethanolamine salts, 0.048. Item 40. Use of a purine nucleic acid-related sub triethanolamine salts, monoisopropanolamine salts, diiso stance and a pyrimidine nucleic acid-related Substance for propanolamine salts, and triisopropanolamine salts, etc., etc. collagen production. Preferable among these are alkali metal salts, such as sodium salts, etc. Specific examples of alkali metal salts include BRIEF DESCRIPTION OF THE DRAWINGS adenosine monophosphate monosodium and adenosine 0049 FIG. 1 is a chart showing the PICP concentration monophosphate disodium. produced when the human skin fibroblasts were cultured in 0055 Such purine nucleic acid-related substances may be media containing various concentrations of AMP2Na in Test used alone or in combination of two or more such species as Example 1. an active ingredient(s) of the composition for promoting 0050 FIG. 2 is a chart showing the PICP concentration collagen production of the invention. produced when the human skin fibroblasts were cultured in 0056. The proportion of purine nucleic acid-related sub media containing various concentrations of AMP2Na and stance usable in the composition for promoting collagen UMP2Na in Test Example 2. production of the invention varies depending on the type of BEST MODE FOR CARRYING OUT THE purine nucleic acid-related Substance, existence and type of INVENTION the pyrimidine nucleic acid-related substance described later, intended use and/or shape of the composition, etc., but (I) Composition for Promoting Collagen Production is usually suitably adjusted within the range 0.01 to 10% by 0051. The composition for promoting collagen produc weight, preferably 1 to 10% by weight, and more preferably tion of the invention comprises a purine nucleic acid-related 3 to 6% by weight. Substance as an active ingredient. The “purine nucleic acid 0057 Preferably, the composition for promoting collagen related substance' used herein refers to purine, various production of the invention comprises, in addition to the purine derivatives having a purine skeleton, and salts above-described purine nucleic acid-related Substance, a thereof. pyrimidine nucleic acid-related Substance. The combined 0.052 There is no limitation on the purine nucleic acid use thereof can further enhance the action of promoting related substances usable in the invention insofar as the collagen production of the purine nucleic acid-related Sub purine nucleic acid-related Substance can be mixed in cos stance. The “pyrimidine nucleic acid-related substance' metics, externally-applied medical/quasi-medical drugs. used herein refers to pyrimidine, various pyrimidine deriva Those that are water soluble or hydrophilic are preferable. In tives having a pyrimidine skeleton, and salts thereof. general, examples of Such purine nucleic acid-related Sub 0058. There is no limitation on the pyrimidine nucleic stances include adenine nucleic acid-related Substances Such acid-related Substances usable in the composition for pro as adenine, adenosine, adenosine phosphates(for example, moting collagen production of the invention insofar as the adenosine 2'-phosphate, adenosine 3'-phosphate, adenosine pyrimidine nucleic acid-related Substance can be mixed in 5'-phosphate, adenosine 5'-diphosphate, adenosine 5'-triph cosmetics, externally-applied medical/quasi-medical drugs. osphate, cyclic adenosine phosphate, adenyloSuccinic acid, Those that are water soluble or hydrophilic are preferable. nicotinamide adenine monodinucleotide (NMN), nicotina Examples of Such pyrimidine nucleic acid-related Sub mide adenine dinucleotide (NAD), nicotinamide adenine stances include uracil nucleic acid-related Substances, such dinucleotide phosphate (NADP), flavinadenine dinucleotide as uracil, uridine, uridine phosphates uridine monophos (FAD), etc.), metabolites thereof (for example, hypoxan phates (uridine 5'-phosphate, uridine 3'-phosphate, and uri thine, inosine, inosinic acid, etc.), and salts thereof, and dine 2'-phosphate), uridine diphosphates, uridine triphos guanine nucleic acid-related Substances such as guanine, phates, cyclic uridine phosphate, etc.), deoxyuridine, guanosine, guanosine phosphates (for example, guanosine deoxyuridine phosphates 5'-deoxyuridine diphosphate 3'-phosphate, guanosine 5'-phosphate, guanosine 5'-diphos (dUDP), 5'-deoxyuridine phosphate(dUMP), etc.), and salts phate and guanosine 5'-triphosphate, etc.), metabolites thereof cytosine nucleic acid-related Substances, such as thereof (for example, Xanthylic acid, Xanthin, etc.), and salts cytosine, cytidine, cytidine phosphates (CMP) cytidine thereof. monophosphates (cytidine 5'-phosphate, cytidine 3'-phos 0053 Among them, preferable examples of the purine phate, cytidine 2'-phosphate), cytidine triphosphate (CTP), nucleic acid-related Substance in the invention include the cytidine diphosphate (CDP)) deoxycytidine, deoxycytidine above-mentioned adenine nucleic acid-related Substances. phosphates (5'-deoxycytidine triphosphate (dCTP), More preferable among these are adenosine phosphates, 5'-deoxycytidine diphosphate (dCDP), 5'-deoxycytidine metabolites thereof, and salts thereof, and particularly pref phosphate (dCMP), etc.) and salts thereof; and thymine erable are adenosine phosphates and salts thereof. Among nucleic acid related-Substances, such as thymine, thymidine, adenosine phosphates, adenosine 2'-phosphate, adenosine thymidine phosphates thymidine monophosphates (dTMP), 3'-phosphate, adenosine 5'-phosphate (AMP) can be suitably thymidine diphosphates (dTDP), thymidine triphosphates used, and adenosine 5'-phosphate (AMP) is particularly (dTTP), etc.), orotic acid, orotidine 5'-phosphate, and salts preferable. thereof. US 2007/01353.74 A1 Jun. 14, 2007
0059 Any pyrimidine nucleic acid-related substances are include Surfactants, colorants (dyes, pigments), flavors, anti usable irrespective of purity insofar as each Such component septics, bactericides (antibacterials), thickeners, antioxi is contained. Usable as pyrimidine nucleic acid-related Sub dants, sequestering agents, refrigerants, deodorizers humec stances are plant extracts containing each Such component, tants, UV absorbers, UV dispersants, vitamins, plant Such as Brassicaceae plant extracts (especially, seed extracts, astringents, anti-inflammatory agents (antiphlogis extracts), Leguminosae plant extracts, etc. tic agents), whiteners, cell activators, vasodilators, blood circulation accelerators, skin function accelerators, and the 0060. The above-mentioned uracil nucleic acid-related like. Substances are preferably used as the pyrimidine nucleic acid-related substances because they can further effectively 0066 Examples of the above-mentioned components enhance the action of promoting collagen production of the include anionic Surfactants, such as salts of higher fatty purine nucleic acid-related Substance. Preferable among the acids, alkylsulfonate salts, polyoxyethylene alkyl ether Sul above are uridine, uridine phosphates, and salts thereof, with fates, alkyl ether phosphates, N-acylamino acid salts, acyl uridine phosphates and salts thereof being more preferable. N-methyl taurine salts, etc.; cationic Surfactants, such as It is preferable to use uridine monophosphate, especially alkyltrimethylammonium chlorides, dialkyldimethylammo uridine 5'-phosphate (UMP), as the uridine phosphate. nium chlorides, etc.; amphoteric Surfactants, such as alky ldimethylaminoacetate betaines, alkylamidedimethylami 0061 Examples of the above-mentioned salts include noacetate betaines, 2-alkyl-N-carboxy-N- Sodium salts, potassium salts, and like alkali metal salts; hydroxyimidazolinium betaines, etc.; nonionic Surfactants, calcium salts, magnesium salts, barium salts, and like alka Such as polyoxyethylene bases, polyhydric alcohol ester line earth metal salts; arginine, lysine, and like basic amino bases, ethylene oxide?propylene oxide block copolymers, acid salts; ammonium salts, tricyclohexylammonium salts, etc. Any high molecular weight Surfactants or natural Sur and like ammonium salts; a wide variety of alkanolamine factants can also be used without limitation. salts, such as monoethanolamine salts, diethanolamine salts, triethanolamine salts, monoisopropanolamine salts, diiso 0067 Examples of antiseptics include ethyl p-hydroxy propanolamine salts, triisopropanolamine salts, etc., etc. benzoate, salicylic acid, Sorbic acid, etc. Examples of thick eners include Xanthane gum, carboxymethyl cellulose 0062 Preferable among these are alkali metal salts such Sodium, carboxy vinyl polymers, etc. Examples of seques as Sodium salts. Specific examples of alkali metal salts tering agents include Sodium salts of ethylenediamine tetra include uridine monophosphate monosodium and uridine acetic acid, phosphoric acid, citric acid, etc. monophosphate disodium. 0068 The composition for promoting collagen produc 0063 Such a pyrimidine nucleic acid-related substance tion of the invention is used as an externally-applied prepa may be used alone or in combination of two or more Such ration to be spread or sprayed to the skin. More specifically, species for the composition for promoting collagen produc the composition for promoting collagen production of the tion of the present invention. invention can be widely used as cosmetics or externally 0064. There is no limitation on the proportion of pyrimi applied medical/quasi-medical drugs (dermatological prepa dine nucleic acid-related Substance usable in the composi rations). Preferable among the above are cosmetics given tion for promoting collagen production of the invention that cosmetics can promote collagen production in the skin insofar as the effect of potentiating the collagen production on a daily basis. Examples of such externally-applied agents can be demonstrated. For example, the proportion of pyri include a wide variety of hair care products such as hair midine nucleic acid-related Substance is suitably adjusted restorers and hair growth agents, as well as, shampoos, within the range of 0.001 to 100 parts by weight per part by rinses, and hair lotions (including tonics and liquids) that weight of purine nucleic acid-related Substance contained in have hair restoration and/or hair growth effects. the composition. The proportion of pyrimidine nucleic acid 0069. The composition for promoting collagen produc related substance is preferably within the range of 0.01 to tion of the invention can take any form without limitation 100 parts by weight, more preferably 0.01 to 10 parts by insofar as it is applicable to the skin or mucosa. Examples weight, and still more preferably 0.01 to 1 part by weight, of form include pastes, mousses, gels, liquids, emulsions, per part by weight of purine nucleic acid-related Substance. Suspensions, creams, ointments, sheets, aerosols, sprays, and The proportion of the pyrimidine nucleic acid-related sub liniments. Examples of cosmetics include lotions; emollient stance based on the total amount of the composition for emulsions, milky lotions, nourishing emulsions, cleansing promoting collagen production is, for example, 0.0001 to emulsions, and like emulsions; emollient creams, massage 10% by weight, preferably 0.0001 to 1% by weight, and creams, cleansing creams, makeup creams, and like creams; more preferably 0.0001 to 0.1% by weight. etc. Examples of hair care products include hair tonics, hair creams, hair lotions, aerosols (air sprays), mousses, sham 0065. The composition for promoting collagen produc poos, rinses, liquids, etc. tion can be formed into various shapes by the combined use of the above-described ingredients with cosmetically or 0070 The composition for promoting collagen produc pharmaceutically acceptable bases, carriers and/or additives. tion of the invention can be directly applied to or sprayed Known cosmetically or pharmaceutically acceptable bases, onto the skin or mucosa as a cosmetic or an externally carriers and/or additives can be used. The composition for applied medical/quasi-medical drug. The composition can promoting collagen production of the invention can com be applied to the skin or mucosa once to 5 or 6 times per day prise, if required, a wide variety of known components used in an amount effective to promote collagen production in externally-applied compositions Suitable for the skin according to the age of the user (human), the gender, the and/or mucosa, Such as cosmetics and externally-applied intended use, the condition of the affected part of the skin, medical/quasi-medical drugs. Examples of such components etc. US 2007/01353.74 A1 Jun. 14, 2007
0071. The composition for promoting collagen produc the following Test Examples, “w/v '%' is a weight (g) per tion of the invention promotes collagen production, and 100 ml unless otherwise specified. therefore exhibits the effects of anti-aging, moisturizing, anti-acne, anti-wrinkle, anti-Sagging, anti-dullness, hair Example 1 growth, anti-dandruff, nail beautifying, wound healing, etc. Thus, the composition for promoting collagen production of Lotion (pH 6.5) the invention can be used as a cosmetic or an externally applied medical/quasi-medical drug for the purpose of anti 0078 aging, moisturizing, anti-acne, anti-Wrinkle, anti-Sagging, anti-dullness, hair growth, anti-dandruff, nail beautifying, wound healing, etc. Among the above, the composition for Adenosine monophosphate disodium 3.0 (% by weight) Uridine monophosphate disodium O.1 promoting collagen production of the invention is advanta Polyoxyethytene (E.0.60) hardened castor oil 0.7 geously useful for externally-applied preparations for the Ethanol S.O purpose of anti-aging, moisturizing, anti-acne, anti-wrinkle, Glycerin 2.0 anti-Sagging, anti-dullness, hair growth, anti-dandruff, nail Antiseptic O.2 Flavor Suitable quantity beautifying, wound healing, etc. In particular, the composi pH adjuster Suitable quantity tion for promoting collagen production of the invention is Purified water Balance useful for various externally-applied preparations for the purpose of anti-wrinkle. Total 100.0% by weight 0072 The composition for promoting collagen produc tion of the invention demonstrates an excellent collagen 0079 A lotion was prepared according to the above production promotion effect when applied to the skin. formulation in a routine manner. Accordingly, the invention provides use of a purine nucleic acid-related Substance for the preparation of compositions Example 2 for promoting collagen production; and use of a purine nucleic acid-related Substance and a pyrimidine nucleic Milky Lotion (pH 6.5) acid-related Substance for the preparation of compositions for promoting collagen production. 0080) (II) Method for Promoting Collagen Production 0073. The present invention also provides a method for Adenosine monophosphate disodium 1.5 (% by weight) Uridine monophosphate disodium O.O1 promoting collagen production. The method is carried out by Carboxyvinyl polymer O.3 applying a purine nucleic acid-related Substance to the skin. Decaglyceryl monomyristate 2.0 Squalane S.O 0074. In the method of the invention, by applying a Ethanol 1.O pyrimidine nucleic acid-related Substance and a purine Glycerin 6.O nucleic acid-related Substance to the skin, the collagen Antiseptic O.2 pH adjuster Suitable quantity production promotion effect becomes more prominent. Purified water Balance 0075 According to the method of the invention, the application of the Substance(s) to the skin can be achieved by Total 100.0% by weight spreading, spraying, or Sticking of the composition for promoting collagen production (I) above to the skin. 0081. A milky lotion was prepared according to the above 0076. In the method of the invention, there is no limita formulation in a routine manner. tion on the frequencies with which a purine nucleic acid related Substance alone or a combination of a purine nucleic Example 3 acid-related Substance and a pyrimidine nucleic acid-related Substance is applied to the skin or the like and also the Hair Restorer application amounts thereof are not limited. For example, 0082 either or both of the substances are applied to the skin in an appropriate amount one to five or six times per day accord ing to the age of the application target, the gender, the Adenosine monophosphate disodium 10.0 (% by weight) intended use, the condition of the affected part of the skin, Uridine monophosphate disodium 1.O etc. More specifically, when the method of the invention is Salicylic acid O.1 carried out by using the composition for collagen production Ethanol 2O.O described in (I) above, a single dose can be suitably adjusted Glycerin 2.O Antiseptic O.2 Such that the amount of the composition applied to the skin Flavor Suitable quantity or the like is within the range of 0.5 to 10 mg/cm. pH adjuster Balance EXAMPLES Total 100.0% by weight 0077. The present invention is described in further detail with reference to Examples and Test Examples. The scope of 0083. A hair restorer was prepared according to the above the invention is not limited to these Examples, however. In formulation in a routine manner. US 2007/01353.74 A1 Jun. 14, 2007
Example 4 on the amount of collagen in the culture Supernatant using a Procollagen type I C-peptide (PIP) EIA Kit (manufactured Milky Lotion (pH 6.5) by Takara Bio Inc.). 0084) 0092 collagen production and is useful for anti-aging, moisturiz Substance is selected from the group consisting of adenosine ing, anti-acne, anti-wrinkle, anti-Sagging, anti-dullness, hair 5'-monophosphate and a salt thereof and the pyrimidine growth, anti-dandruff, nail beautifying, wound healing, etc. nucleic acid-related Substance is at least one member 1. A composition for promoting collagen production, selected from the group consisting of uridine 5'-monophos comprising a purine nucleic acid-related Substance and a phate and a salt thereof. pyrimidine nucleic acid-related Substance. 12. A composition for promoting collagen production 2. (canceled) according to claim 1, wherein the composition contains the 3. A composition for promoting collagen production pyrimidine nucleic acid-related Substance in a proportion of according to claim 1, wherein the purine nucleic acid-related 0.001 to 100 parts by weight per part by weight of the purine Substance is at least one member selected from the group nucleic acid-related Substance. consisting of adenine, adenosine, adenosine phosphate, a 13. A composition for promoting collagen production metabolite of adenosine phosphate, and a salt thereof. according to claim 1, wherein the composition contains the 4. A composition for promoting collagen production purine nucleic acid-related substance in a proportion of 0.01 according to claim 1, wherein the purine nucleic acid-related to 10% by weight based on the total amount of the compo Substance is at least one member selected from the group sition. consisting of adenosine monophosphate and a salt thereof. 14. A composition for promoting collagen production 5. A composition for promoting collagen production according to claim 1, wherein the composition contains the according to claim 1, wherein the purine nucleic acid-related pyrimidine nucleic acid-related Substance in a proportion of Substance is at least one member selected from the group 0.0001 to 10% by weight based on the total amount of the consisting of adenosine 5'-monophosphate and a salt thereof. composition. 6. A composition for promoting collagen production 15. A composition for promoting collagen production according to claim 1, wherein the pyrimidine nucleic acid according to claim 1 used for a cosmetic, or an externally related substance is at least one member selected from the applied medical or quasi-medical drug. group consisting of uracil, uridine, uridine phosphate, and a 16. A method for promoting collagen production, com salt thereof. prising applying to the skin a purine nucleic acid-related 7. A composition for promoting collagen production Substance and a pyrimidine nucleic acid-related Substance. 17. (canceled) according to claim 1, wherein the pyrimidine nucleic acid 18. A method for promoting collagen production accord related substance is at least one member selected from the ing to claim 16, comprising applying to the skin the com group consisting of uridine monophosphate and a Salt position for promoting collagen production of claim 1. thereof. 19. (canceled) 8. A composition for promoting collagen production 20. Use, for preparation of a composition for promoting according to claim 1, wherein the pyrimidine nucleic acid collagen production, of at least one purine nucleic acid related substance is at least one member selected from the related Substance selected from the group consisting of group consisting of uridine 5'-monophosphate and a salt adenosine 5'-monophosphate and a salt thereof. thereof. 21. Use of a purine nucleic acid-related Substance and a 9. A composition for promoting collagen production pyrimidine nucleic acid-related Substance for preparation of according to claim 1, wherein the purine nucleic acid-related a composition for promoting collagen production. Substance is at least one member selected from the group consisting of adenine, adenosine, adenosine phosphate, a 22. A composition for promoting collagen production, metabolite of adenosine phosphate, and a salt thereof and the comprising at least one purine nucleic acid-related Substance pyrimidine nucleic acid-related Substance is at least one selected from the group consisting of adenosine 5'-mono member selected from the group consisting of uracil, uri phosphate and a salt thereof. dine, uridine phosphate, and a salt thereof. 23. A composition for promoting collagen production 10. A composition for promoting collagen production according to claim 22, wherein the composition contains the according to claim 1, wherein the purine nucleic acid-related purine nucleic acid-related substance in a proportion of 0.01 Substance is selected from the group consisting of adenosine to 10% by weight based on the total amount of the compo monophosphate and a salt thereof and the pyrimidine nucleic sition. acid-related Substance is at least one member selected from 24. A method for promoting collagen production, com the group consisting of uridine monophosphate and a salt prising applying to the skin at least one purine nucleic thereof. acid-related Substance selected from the group consisting of 11. A composition for promoting collagen production adenosine 5'-monophosphate and a salt thereof. according to claim 1, wherein the purine nucleic acid-related k k k k k