WO2002072039A2 - Topical preparations and food preparations comprising a pyridoxine-alpha-d-glucose - Google Patents
Topical preparations and food preparations comprising a pyridoxine-alpha-d-glucose Download PDFInfo
- Publication number
- WO2002072039A2 WO2002072039A2 PCT/EP2002/002599 EP0202599W WO02072039A2 WO 2002072039 A2 WO2002072039 A2 WO 2002072039A2 EP 0202599 W EP0202599 W EP 0202599W WO 02072039 A2 WO02072039 A2 WO 02072039A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- derivatives
- preparation
- pyridoxine
- acid
- extracts
- Prior art date
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- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
- 229940057995 liquid paraffin Drugs 0.000 description 2
- 239000000711 locust bean gum Substances 0.000 description 2
- 235000010420 locust bean gum Nutrition 0.000 description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 229960002216 methylparaben Drugs 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 235000018343 nutrient deficiency Nutrition 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 238000004445 quantitative analysis Methods 0.000 description 2
- 208000008742 seborrheic dermatitis Diseases 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- FDCJDKXCCYFOCV-UHFFFAOYSA-N 1-hexadecoxyhexadecane Chemical compound CCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCC FDCJDKXCCYFOCV-UHFFFAOYSA-N 0.000 description 1
- XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- SBASXUCJHJRPEV-UHFFFAOYSA-N 2-(2-methoxyethoxy)ethanol Chemical compound COCCOCCO SBASXUCJHJRPEV-UHFFFAOYSA-N 0.000 description 1
- 241001116389 Aloe Species 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 244000000626 Daucus carota Species 0.000 description 1
- 235000002767 Daucus carota Nutrition 0.000 description 1
- 108010073178 Glucan 1,4-alpha-Glucosidase Proteins 0.000 description 1
- 102100022624 Glucoamylase Human genes 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- 239000005913 Maltodextrin Substances 0.000 description 1
- 241000192041 Micrococcus Species 0.000 description 1
- CKLZLRJBBVUVFN-OXBJBCBCSA-N O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO.N1=C(C)C(O)=C(CO)C(CO)=C1 Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO.N1=C(C)C(O)=C(CO)C(CO)=C1 CKLZLRJBBVUVFN-OXBJBCBCSA-N 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000222180 Pseudozyma tsukubaensis Species 0.000 description 1
- 241000235545 Rhizopus niveus Species 0.000 description 1
- 241000952054 Rhizopus sp. Species 0.000 description 1
- 241000235004 Saccharomycopsis fibuligera Species 0.000 description 1
- 241000192023 Sarcina Species 0.000 description 1
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- PFZXGXCGOJDNRF-UHFFFAOYSA-N [5-hydroxy-4-(hydroxymethyl)-6-methylpyridin-3-yl]methyl hexadecanoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC1=CN=C(C)C(O)=C1CO PFZXGXCGOJDNRF-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 235000011399 aloe vera Nutrition 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- ADCGAPKUMAQOLJ-UHFFFAOYSA-N azane;formic acid Chemical compound N.OC=O.OC=O ADCGAPKUMAQOLJ-UHFFFAOYSA-N 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 230000003780 keratinization Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 1
- WHOMFKWHIQZTHY-UHFFFAOYSA-L pyridoxine 5'-phosphate(2-) Chemical compound CC1=NC=C(COP([O-])([O-])=O)C(CO)=C1O WHOMFKWHIQZTHY-UHFFFAOYSA-L 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 235000011076 sorbitan monostearate Nutrition 0.000 description 1
- 239000001587 sorbitan monostearate Substances 0.000 description 1
- 229940035048 sorbitan monostearate Drugs 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000019158 vitamin B6 Nutrition 0.000 description 1
- 239000011726 vitamin B6 Substances 0.000 description 1
- 150000003697 vitamin B6 derivatives Chemical class 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/60—Sugars; Derivatives thereof
- A61K8/602—Glycosides, e.g. rutin
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/15—Vitamins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/673—Vitamin B group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/08—Antiseborrheics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/002—Aftershave preparations
Definitions
- the present invention refers to topical dermal preparations and food preparations containing pyridoxine- ⁇ -D-glucoside as an active ingredient. These preparations are suitable for use as drugs, quasi-drugs or cosmetics.
- the topical dermal preparations in particular are useful in preventing or treating rough skin or slowing the ageing of the skin by preventing loss of lustrous complexion from the skin.
- Damaged skin is commonly called dry skin or rough skin.
- dry skin has been treated with topical agents containing moisturizing agents such as hyaluronic acid and various types of ceramide in order to provide water to the corneum, while natural extracts such as aloe, placenta and carrot extracts, allantoin, and fermentation metabolites have been used to deal with rough skin associated with physiological keratinization abnormality.
- Vitamin B6 or pyridoxine, was discovered as a substance which prevents skin diseases. Its derivatives such as pyridoxine HCl, pyridoxine tripalmitate and pyridoxine dioctanoate have been expected to be effective as topical agents. However, these vitamin B6 derivatives present the problems reported below.
- pyridoxine HCl is extremely unstable in topical preparations. Pyridoxine tripalmitate and pyridoxine dioctanoate, which are fat-soluble, are not effective enough probably due to their poor solubility in water. Pyridoxine seems to be empirically used in topical preparations simply because it is believed to be effective in preventing and improving seborrheic dermatitis caused by nutritional deficiency of pyridoxine.
- the objective of this invention is to supply topical dermal and food preparations which are pharmaceutically stable and suitable for use as drugs, quasi-drugs or cosmetics which are useful in preventing or treating rough skin or slowing the ageing of the skin by preventing loss of lustrous complexion from the skin.
- pyridoxine- (X-D-glucoside, a pyridoxine derivative, can be an active ingredient which makes it possible to achieve the objective and have completed this invention.
- the present invention is defined in the claims.
- the present invention particularly refers to a topical dermal preparation and a food preparation, being suitable for use as a drug, a quasi-drug, a cosmetic, a food or a food additive, which are characterized in that said preparations comprize at least one pyridoxine-(X-D- glucoside. Said preparations optionally may comprize further additives.
- the present invention further refers to the use of said preparation for preventing or treating rough skin or slowing the ageing of the skin by preventing loss of lustrous complexion from the skin.
- the present invention further refers to said topical dermal preparations in the form of ointments, creams, poultices, adhesive agents, liquid preparations, aerosols, liniments, and lotions.
- the present invention further refers to said food preparations in the form of a semi-solid, a liquid, or an aerosol, to be used as a food-additive or processed food.
- the present preparation may represent a prescribed or a nonprescribed drug, cosmetic or a processed food containing a liquid base.
- the present invention further refers to said preparation which further comprizes oc-arbutin.
- the topical dermal preparations under the present invention preferably contain pyridoxine- ⁇ -D-glucoside in an amount of 0.05-20.0% (w/w) , and optionally ⁇ -arbutin preferably in an amount of 0.05-10.0% (w/w), calculated to the weight of the preparation.
- pyridoxine-OC-D-glucoside used in the present invention is different from that expected for pyridoxine conventionally used in topical agents to prevent or improve seborrheic dermatitis caused by nutritional deficiency of pyridoxine; it is used to activate the physiological activity of the skin.
- Pyridoxine analogues and derivatives used in topical agents described in existing patent gazettes and other documents are pyridoxine HCl, pyridoxine palmitate, pyridoxine dioctanoate, and pyridoxine phosphate as is specifically mentioned in these documents, and not pyridoxine- ⁇ X-D- glucoside.
- the topical dermal preparations under the present invention are characterized by the fact that they contain pyridoxine-(X-D-glucoside, a pyridoxine derivative different from those described in the existing patent gazettes and other documents.
- Pyridoxine-0(-D-glucoside has the structural formula shown below.
- the present invention uses pyridoxine-4 • - 0,-D-glucoside (PN-4'-G) or pyridoxine-5 ' -0(-D-glucoside (PN-S'-G) alone or as a mixture of any ratio (PN- ⁇ -D-G) .
- Suzuki at al (1993) reported a method that produces pyridoxine- ⁇ (-D-glucoside from ucor javanicus-derived 0(-glucosidase using dextrin as a sugar donor with a glucosidization rate of 35% (Y. Suzuki et al.: J. Appl. Glycosci., 43 (3), 369-372 (1996)). This was followed by a report by Suzuki et al.
- the inventors have succeeded in establish a commercially useful technology that can be used to produce pyridoxine- ⁇ -D-glucoside in an industrial scale (Mem. Grad. School. Sci. & Technol., Kobe Univ., 17-A: 37-45 (1999)).
- CGTase Bacillus stearothermophilus-derived cyclomaltodextringlucanotransferase
- pH 4.0-8.0 preferably 4.5-5.5
- reaction temperature 30-70°C pre- ferably 55-65°C.
- CGTase is also very stable under these conditions.
- the degree of maltdextrin polymerization should be 4-25, preferably 6-13, and the substrate concentration should be 4-12% for pyridoxine HCl and 0.05- 0.10 mol/L for maltdextrin (L, liter; mL, milliliter; ⁇ , micro liter) .
- the reaction fluid also contains pyridoxine- ⁇ -maltoglyco- side. This is also physicochemically stable and is useful, but the ratio of pyridoxine in the active moiety in its molecule is small.
- the yield can be increased by converting pyridoxine-(X-maltoglycoside contained in the reaction fluid to pyridoxine-(X-D-glucoside using glucoamylase derived from Rhizopus sp. such as Rhizopus niveus, Saccharomycopsis fibuligera, and Candida tsukubaensis.
- Pyridoxine- 0,-D-glucoside obtained by the above-mentioned enzymatic methods can be purified as shown below.
- the reaction fluid obtained in the production of pyridoxine-Ot-D-glucoside from Bacillus stearothermophilus- derived CGTase under the optimal conditions shown above using commercial pyridoxine HCl as a receptor and commercial maltdextrin as a sugar donor contains pyridoxine which has not yet reacted.
- This reaction fluid can be completely separated into pyridoxine and pyridoxine-(X-D-glucoside (PN- ⁇ -D-G) by treating it by gel filtration column chromatography (using fillers such as Sephadex LH-20 (Pharmacia Biotech)) using an appropriate solvent (such as 20% methanol) . This separation procedure may be repeated to increase the purity although one cycle is sufficient.
- the separated product is a 2:1 mixture of PN-4 ' -G and PN- 5 ' -G on a molar basis. These two ingredients can be separated, if necessary, by treating the mixture by column chromatography using an appropriate solvent. Usable methods include Cosumosil 75C18-OPN (Nacalai Tesque) column chromatography using 10% ethanol and Dowex 50Wx8 (Dow Chemical) column chromatography using formic acid- ammonium formate buffer solution containing 40% ethanol. Operations should be repeated to increase purity.
- the separation and purification methods described above can be applied to pyridoxine-(X-D-glucoside produced by Bacillus stearothermophilus-derived CGTase and Bacillus macerans-derived ⁇ (-glucosidase.
- the singlet signal at 7.87 ppm is assigned to the proton directly bound to position 6 of pyridoxine; the doublet signal at 4.87 ppm to one of the two protons at position 4 " of pyridoxine; the doublet signal at 4.74 ppm to the proton at position 1' of glucose; the double signal at 4.53 ppm to another proton at position 4' of pyridoxine; the singlet signal at 4.46 ppm to 2 protons at position 5* of pyridoxine; the multiplet signal at 3.59-3.06 ppm to 6 protons at positions 2', 3', 4', 5' and 6'; and the singlet signal at 2.30 ppm to 3 protons at position 2' of pyridoxine.
- protons of the hydroxymethyl group at position 4 of pyridoxine are not equivalent and are found separated into 2 signals indicates that the glucose is bound at position 4' and that PN-4'-G is 0(-bound with the anomeric proton of glucoside showing a small coupling constant (J: 3.4Hz).
- the assignment of major signals on the "' ⁇ H-NMR spectrum of the other ingredient is as follows: the singlet at 4.76 ppm is assigned to 2 protons at position 4' of pyridoxine; the doublet at 4.69 ppm to one of the 2 protons at position 5* of pyridoxine; and the doublet at 4.48 ppm to the other proton at position 5' of pyridoxine.
- pyridoxine-Of-D-glucoside in topical dermal preparations under the present invention is not specified and can be set at any level depending on their intended applications. In general, however, it is desirable to be 0.05-20.0% (w/w).
- additives commonly used in the production of drugs, quasi-drugs and cosmetics for topical application can be added to the topical dermal preparations under the present invention, such as moisturizing agents, UV protecting agents, whitening agents, antioxidants, viscosity donors, surface active agents, alcohol, aqueous ingredients, pigments, sequestrants, and skin nutrients.
- whitening agents such as arbutin, 0_-arbutin (hydroquinone-0(-D-glucoside) , 4-n-butylresorcinol, ascorbic acid, magnesium phosphate ascorbate, glucoside ascorbate, kojic acid, glucoside kojiate, and placenta extract, various crude drugs, ceramide, substances with ceramide-like structures, pantlacton, pantethine, pantethine-S- sulfonate and its salts, GABGA, epsilon- aminocaproic acid, tranexamic acid, vitamin E and its esters or derivatives, glycyrrhetic acid and its derivatives or salts, and saccharide such as trehalose.
- arbutin 0_-arbutin (hydroquinone-0(-D-glucoside) , 4-n-butylresorcinol, ascorbic acid, magnesium phosphate as
- Topical dermal preparations may contain pyridoxine- ⁇ -D-glucose and at least one compound selected from ascorbic acid and its derivatives, galenicals and their extracts, hydroxycarboxylic acid and its salts, oil- soluble Glycyrrhiza extracts, gentian extracts, phenol derivatives and their salts, placenta extracts, kojic acid and its derivatives, glucosa ine and its derivatives, azelaic acid and its derivatives, retinol and its derivatives, hydroquinone glycoside, tocopherol and its derivatives, vitamin E-nicotinate, diisopropylamine dichloroacetate, chitosan and its degradation products, caffeic acid derivatives, hydroxycinnamic acid and its derivatives, Umbelliferae extracts, mycelial culture and its extracts, plant leaves and their extracts, plant stem bark and its extracts, hinokitiol, ginseng extracts,
- UV-absorbers ⁇ -pyrone glycoside, hydroxy-salicylic acid glycoside, hydroxysalicylic acid aliphatic ester glycoside, biphenyl compounds, ceramides, ceramide analogues, ether compounds described in a general formula of R 1 -0-(X-0)n-R 2 (wherein Rj and R 2 are identical or different and represent a Ci.1 ⁇ 2 straight chained, branched or cyclic alkyl group, X being C ⁇ _i 2 alkylene group, n being 0 or 1, and the total C-number of R l R 2 and X being 10-32) , pantothenic acid and its derivatives, sodium hydrogen sulfite, antiphlogistics, allantoin and its derivatives, amino acids and their derivatives, aminoethyl compounds, alkylenediaminecarboxylic acid derivatives, betaine derivatives, acylmethyltaurine, fibronectine, anti-tyrosinase
- the pyridoxine- ⁇ -D-glucoside may be, as described above, pyridoxine-4- ⁇ -D-glucoside or pyridoxine-5 ' - ⁇ -D-glucoside alone or a mixture thereof at any mixing ratio.
- Preparations or foods that contain pyridoxine glycoside contain pyridoxine- ⁇ -D-glucoside, and may be semi-solid, liquid or aerosol-type prescribed or non-prescribed drugs, cosmetics or processed foods. These preparations or foods may represent prescribed or non- prescribed drugs, cosmetics or processed foods which contain a liquid base.
- pyridoxine-O.- D-glucoside be added at 0.05-20.0% (w/w) and 0(-arbutin at 0.05-10.0% (w/w).
- pyridoxine- ⁇ (-D-glucoside and 0(-arbutin on the skin are not affects.
- their effects are enhanced and their ability to prevent or improve rough skin and slow down the skin ageing process by preventing the loss of lustrous complexion of the skin is increased.
- topical dermal preparations under the present invention that contain the above-mentioned ingredients can be manufactured in known manner and with known methods in various dosage forms such as ointment, cream, poultices, adhesive agents, liquid preparations, aerosol, liniments, and lotion.
- dosage forms such as ointment, cream, poultices, adhesive agents, liquid preparations, aerosol, liniments, and lotion.
- the following Examples illustrate the present invention.
- a mixture of purified water and propylene glycol was prepared at the ratio shown in Table 1, and PN-0.-D-G, methyl parahydroxybenzoate and butyl parahydroxybenzoate were added at the ratio shown in Table 1. The mixture was then dissolved by heating at 80°C.
- PN-0(-G was dissolved in purified water at the ratio shown in Table 2 , and the solution obtained was heated to and maintained at 70°C. The solution obtained was added to a mixture of all other ingredients prepared at the ratio shown in Table 2 and dissolved by heating at 70°C and maintained at this temperature. The mixture obtained was thoroughly stirred and cooled to prepare a cream.
- PN-0.-G was dissolved in purified water at the ratio shown in Table 3 , and the solution obtained was heated to and maintained at 70°C.
- the solution obtained was added to a mixture of all other ingredients prepared at the ratio shown in Table 3 and dissolved by heating at 70°C and maintained at this temperature.
- the mixture obtained was thoroughly stirred, cooled to 50°C, homogenized, and then cooled to 30°C.
- Locust bean gum was added to the homogenate at the ratio shown in Table 3, stirred, and cooled to prepare a cream.
- Sample A containing 5.0% (w/w) PN-0(-D-G (same as used in Working Example 1), Sample B containing 5.0% (w/w) placenta extract (manufactured by Pentapharm Corporation) , and Sample C not containing either PN-0C-D-G or placenta extract were prepared in accordance with the formula of the cream prepared in Working Example 2. The ability of these preparations to improve rough skin and rash caused by shaving was evaluated as mentioned below. Improvement of rough skin
- the test was conducted in 50 female volunteers with rough skin. Sample A or B was applied to the cheek on one side and Sample C containing no active ingredient was applied to the cheek on the other side. About 0.3 g was applied twice a day for 3 weeks. The skin condition was examined and evaluated after completion of the treatment. Findings obtained are reported in Table 4. The efficacy was classified into one of the following 4 categories: Markedly effective: symptoms disappeared and the skin recovered lustrous complexion.
- the cream containing pyridoxine- ⁇ -D- glucoside showed marked efficacy for rough skin.
- the test was conducted in 45 male volunteers with rash due to shaving divided into 3 groups of 15 volunteers. Volunteers were asked to shave once a day and apply Sample A, B or C immediately after shaving. The test was conducted for 1 week and the effect of the samples on rash due to shaving was examined. Findings obtained are reported in Table 5. The efficacy was classified into one of the following 4 categories:
- the cream containing pyridoxine-OC-D- glucoside was effective for rash due to shaving.
- the stability of the cream prepared as shown in Working Example 2 was determined using the volumes shown below in order to evaluate the stability of topical dermal preparations under the present invention.
- a topical dermal preparation containing 0.5% (w/w) PN-0.-D- G was prepared using the formula shown in Working Example 2.
- the cream obtained was transferred into plastic containers, lOg per container, packed in aluminum foil, and kept at constant temperature of 50°C for 0, 30 and 90 days (accelerated stability study) , and the stability was evaluated.
- Table 6 Data presented in Table 6 are means of values determined in triplicate and show residual percentages for PN- ⁇ -D-G (sum or PN-4'-G and PN-5'-G) and pyridoxine.
- pyridoxine- ⁇ (-D-glucoside under the present invention is compatible with many ingredients, it can be easily formulated into topical dermal preparations for use as drugs, quasi-drugs and cosmetics.
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Abstract
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Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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AU2002308248A AU2002308248A1 (en) | 2001-03-09 | 2002-03-08 | Topical preparations and food preparations comprising a pyridoxine-alpha-d-glucose |
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP13/67587 | 2001-03-09 | ||
JP13/067586 | 2001-03-09 | ||
JP2001067586A JP2002265316A (en) | 2001-03-09 | 2001-03-09 | Skin care preparation |
JP2001067587A JP2002265368A (en) | 2001-03-09 | 2001-03-09 | Pyridoxine glycoside-containing preparation or food |
JP14/016113 | 2002-01-24 | ||
JP2002016113A JP2006169111A (en) | 2002-01-24 | 2002-01-24 | External preparation for skin |
Publications (2)
Publication Number | Publication Date |
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WO2002072039A2 true WO2002072039A2 (en) | 2002-09-19 |
WO2002072039A3 WO2002072039A3 (en) | 2002-11-28 |
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Application Number | Title | Priority Date | Filing Date |
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PCT/EP2002/002599 WO2002072039A2 (en) | 2001-03-09 | 2002-03-08 | Topical preparations and food preparations comprising a pyridoxine-alpha-d-glucose |
Country Status (2)
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AU (1) | AU2002308248A1 (en) |
WO (1) | WO2002072039A2 (en) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1679316A1 (en) * | 2003-10-01 | 2006-07-12 | Daiichi Fine Chemical Co., Ltd. | Stable vitamin b6 derivative |
WO2006120646A1 (en) * | 2005-05-13 | 2006-11-16 | Sederma | Topical use of teprenone |
DE102007041475A1 (en) * | 2007-08-31 | 2009-03-05 | Beiersdorf Ag | Active ingredient combination of glycyrrhetinic acid and erythrulose and cosmetic or dermatological preparations containing this combination of active ingredients |
EP2174643A1 (en) | 2008-10-13 | 2010-04-14 | Johnson & Johnson Consumer France SAS | Self tanning compositions containing dihydroxyacetone, a retinoid and ascorbic acid glucoside as a stabilizer |
DE102009048977A1 (en) * | 2009-10-09 | 2011-04-14 | Beiersdorf Ag | Cosmetic or dermatological preparations with combinations of 4-n-butylresorcinol and one or more sulfites, in particular hydrogen sulfites and / or disulfites |
US8318786B2 (en) | 2007-08-16 | 2012-11-27 | The University Of Chicago | Plant pathogen resistance |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2001091715A2 (en) * | 2000-06-02 | 2001-12-06 | Pentapharm Ltd. | Topical agent for dermatological use containing 4-hydroxyphenyl-alpha-d-glucopyranoside |
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JPS4633198B1 (en) * | 1967-04-04 | 1971-09-28 | ||
JPS4918230B1 (en) * | 1968-09-20 | 1974-05-08 | ||
JPH05932A (en) * | 1991-06-26 | 1993-01-08 | Kurabo Ind Ltd | Agent for artificial suntan |
JPH0736758B2 (en) * | 1992-05-15 | 1995-04-26 | 倉敷紡績株式会社 | Method for producing polyphenol glycoside |
-
2002
- 2002-03-08 WO PCT/EP2002/002599 patent/WO2002072039A2/en active Application Filing
- 2002-03-08 AU AU2002308248A patent/AU2002308248A1/en not_active Abandoned
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001091715A2 (en) * | 2000-06-02 | 2001-12-06 | Pentapharm Ltd. | Topical agent for dermatological use containing 4-hydroxyphenyl-alpha-d-glucopyranoside |
Non-Patent Citations (5)
Title |
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CHEMICAL ABSTRACTS, vol. 118, no. 175535, 1993 Columbus, Ohio, US; abstract no. 1993175535, FUNAYAMA,, M., NISHINO, T.: "Suntanning agents containing hydroquinone-O-alpha-D-glucopyranoside" XP002193690 & JP 05 000932 A (KURASHIKI SPINNING CO.) 8 January 1993 (1993-01-08) * |
DATABASE CA [Online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; FUNAYAMA, MASATAKA ET AL: "Manufacture of polyphenol glycosides with amylase" retrieved from STN Database accession no. 122:54160 XP002214171 & JP 06 284896 A (KURASHIKI BOSEKI KK, JAPAN) 11 October 1994 (1994-10-11) * |
DATABASE CA [Online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; OGATA, KOHICHI: "Pyridoxine glucoside" retrieved from STN Database accession no. 82:84470 XP002214170 & JP 49 018230 B (OGATA, KOHICHI) 8 May 1974 (1974-05-08) * |
DATABASE CA [Online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; OGATA, KOICHI: "Microbial conversion of pyridoxine to its glucoside" retrieved from STN Database accession no. 76:2556 XP002214169 & JP 46 033198 B (OGATA, KOICHI) 28 September 1971 (1971-09-28) * |
SUZUKI, Y.; DOI, Y.; UCHIDA, K.; TSUGE, H.: "Preparation of two Pyridoxine-alpha-Glucosides by alpha-Glucosidase" OYO TOSHITSU KAGAKU (J. APPL. GLYCOSCI.), vol. 43, no. 3, 1996, pages 369-372, XP002214168 cited in the application * |
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1679316A4 (en) * | 2003-10-01 | 2010-05-26 | Daiichi Fine Chem Co Ltd | Stable vitamin b6 derivative |
CN100460414C (en) * | 2003-10-01 | 2009-02-11 | 第一精密化学株式会社 | Stable vitamin B6 derivative |
EP1679316A1 (en) * | 2003-10-01 | 2006-07-12 | Daiichi Fine Chemical Co., Ltd. | Stable vitamin b6 derivative |
EP2311847A1 (en) * | 2003-10-01 | 2011-04-20 | Daiichi Fine Chemical Co., Ltd. | Composition containing stable vitamin B6 derivative |
US8003615B2 (en) | 2003-10-01 | 2011-08-23 | Daiichi Fine Chemical Co., Ltd. | Stable vitamin B6 derivative |
KR101073303B1 (en) * | 2003-10-01 | 2011-10-12 | 다이이치 파인 케미칼 가부시키가이샤 | Stable vitamin B6 derivative |
WO2006120646A1 (en) * | 2005-05-13 | 2006-11-16 | Sederma | Topical use of teprenone |
FR2885522A1 (en) * | 2005-05-13 | 2006-11-17 | Sederma Soc Par Actions Simpli | COSMETIC OR DERMOPHARMACEUTICAL COMPOSITION CONTAINING TEPRENONE |
US8318786B2 (en) | 2007-08-16 | 2012-11-27 | The University Of Chicago | Plant pathogen resistance |
US9161533B2 (en) | 2007-08-16 | 2015-10-20 | The University Of Chicago | Plant pathogen resistance |
DE102007041475A1 (en) * | 2007-08-31 | 2009-03-05 | Beiersdorf Ag | Active ingredient combination of glycyrrhetinic acid and erythrulose and cosmetic or dermatological preparations containing this combination of active ingredients |
EP2174643A1 (en) | 2008-10-13 | 2010-04-14 | Johnson & Johnson Consumer France SAS | Self tanning compositions containing dihydroxyacetone, a retinoid and ascorbic acid glucoside as a stabilizer |
DE102009048977A1 (en) * | 2009-10-09 | 2011-04-14 | Beiersdorf Ag | Cosmetic or dermatological preparations with combinations of 4-n-butylresorcinol and one or more sulfites, in particular hydrogen sulfites and / or disulfites |
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WO2002072039A3 (en) | 2002-11-28 |
AU2002308248A1 (en) | 2002-09-24 |
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