WO2006133828A1

WO2006133828A1 - Novel use 25-hydroxycholecalciferol in combination with uv-b screening agents

Info

Publication number: WO2006133828A1
Application number: PCT/EP2006/005399
Authority: WO
Inventors: Helmut Luther; Roland Jermann
Original assignee: Dsm Ip Assets B.V.
Priority date: 2005-06-17
Filing date: 2006-06-07
Publication date: 2006-12-21

Abstract

The present invention relates to the use of 25-hydroxycholecalcif erol as an active ingredient in the manufacture of topical compositions which contain a UV-B screening agent for the prevention of vitamin D deficiencies caused by the topical application of such UV-B screening agents, and for increased skin regeneration and cosmetic treatment of skin damages caused by environmentally-induced noxious impact.

Description

NOVEL USE 25-HYDROXyCHOLECALCIFEROL IN COMBINATION WITH UV-B SCREENING AGENTS

The present invention relates to a novel use of 25-hydroxycholecalciferol. More particularly, the invention relates to the use of 25-hydroxycholecalciferol as an active ingredient in the manufacture of topical compositions which contain a UV-B screening agent for the prevention of vitamin D deficiencies caused by the topical application of such UV-B screening agents.

The normal human diet provides no sufficient source to cover the physiological requirement of vitamin D. However, vitamin D (chotecalciferol) is normally produced in sufficient quantity in the skin. By the action of UV radiation in the range of 290-320 nm (UV-B), 7- dehydrocholesterol is converted in the skin to pre-vitamin D3 which, subsequently, is converted in the skin to vitamin D3 and to the physiologically relevant metabolites 25- hydroxycholecalciferol and 1α,25-dihydroxycholecalciferol in the liver and kidney, respectively. It has been found that the UV-induced path from 7-dehydrocholesterol via 25- hydroxycholecalciferol to 1α,25-dihydroxycholecalciferol can also take place in the skin under physiological conditions (Lehmann et al., Hormone Research 2000 54 312-315). Keratinocytes are able to convert 25-hydroxycholecalciferol to 1α,25-dihydroxycholecalci- ferol (Bikle et al., J. Clin. Invest. 1986, 78, 557-566) which may then act locally.

It is known that lack of UV light, for the reasons set forth above, causes vitamin D deficiencies. Particular examples of such deficiencies are negative effects on the immune system and the bone system. Vitamin D insufficiency is an established risk factor for osteoporosis and is related to a number of disorders frequently observed among the eldery, such as breast, prostate and colon cancers, and cardiovascular disorders including hypertension (Mosekilde, Clin. Endocrinol. 2005; 62 (34), 265-281). Since vitamin D metabolites have a positive impact on wound healing and exert relevant activities for cell growth and cell differentiation, apoptosis, malignant cell invasion and metastasis it is highly desirable to avoid vitamin D deficiencies. It has been reported that the main effect of vitamin D and its metabolites may be to prevent the development of malignancy. Epidemiological studies have been disclosed that the mortality of a number of malignant diseases is reduced with increasing UV-B radiation intensity (Mosekilde, I.e.)

On the other hand, it is known that UV radiation may cause various damage to the skin, such as erythema, increased incidence of carcinomas and premature skin aging. To avoid such effects of UV radiation, cosmetic sun protection formulations including day creams containing UV screening agents are used to an increasing extent. The daily use of cosmetic formulations containing UV screening agents, however, blocks the physiological formation of vitamin D and its biologically active derivatives, (see Matsuoka et al., J. Am. Acad, of Dermatology 1990, 22, 772-775). Japanese patent publication No. 5-246835 discloses topical formulations containing certain UV absorbers and vitamin D or derivatives or analogues thereof which are intended to protect the skin from UV radiation and to regenerate the skin after sunburn.

In contradistinction thereto the present invention relates to a method of preventing vitamin D deficiencies when using cosmetic UV sunscreen formulations.

Thus, in one aspect, the present invention relates to the use of 25-hydroxycholecalciferol as an active ingredient in the manufacture of topical compositions which contain a UV-B screening agent, for the prevention of vitamin D deficiencies caused by the topical application of such UV-B screening agents. In another aspect, the present invention relates to a method of preventing vitamin D deficiencies in a person which uses a topical composition containing a UV-B screening agent, which comprises providing to that person a topical composition which contains, besides said UV-B screening agent, an effective amount of 25-hydroxycholecalciferol. The term UV-B screening agent as used herein refers to agents which can be used in topical compositions and which absorb radiation in the 290-320 nm range. Accordingly, said term includes broad spectrum screening agents which also are effective in absorbing radiation beyond the 290-320 nm range. Conditions resulting from vitamin D deficiencies are reduced activities of the skin immune system, or delayed cure of skin irritations of different causes. Thus, the compositions obtainable by the present invention can be used for the treatment and, in particular, for the prevention of said conditions, as well as for increased skin regeneration, and for cosmetic treatment of skin damages caused by environmentally- induced noxious impact.

The topical compositions to which 25-hydroxycholecalciferol is added in accordance with the invention, contain typically about 3 to about 40 per cent by weight (wt.-%) preferably about 5 to about 30 wt.-% of a UV-B screening agent. An effective amount of 25- hydroxycholecalciferol for use in the present invention, i.e. the amount of 25- hydroxycholecalciferol added to such compositions is from about 0.0001 to about 1.0 wt.-% , particularly from about 0.001 to about 0.1 wt.-%, preferably from about 0.01 to about 0.1 wt.-%, and more preferably from about 0.01 to about 0.05 wt.-%, based on the total weight of the composition.

Examples of UV-B screening agents are p-methoxy-cinnamic acid derivatives such as octyl methoxycinnamate; camphor derivatives such as 4-Methylbenzylidene Camphor; siloxane-based sunscreens such as benzylidene malonate polysiloxane and Drometrizole Trisiloxane; p-aminobenzoic acid or derivatives thereof; salicylic acid derivatives such as homosalate or Octylsalicylate; Triazines such as Octyl Triazone, Diethylhexylbutamide Triazone, 2,4,6-Tris-biphenyl-4-yl-[1 ,3,5]triazine or Bis- Ethylhexyloxyphenol Methoxyphenyl Triazine and Octocrylene, Methylene bis- benzotriazolyl tetramethylbutylphenol, Zinc Oxide, Titanium Dioxide;or mixtures thereof.

25-Hydroxycholecalciferol may be used in accordance with the present invention any type of topical formulations comprising a UV-B sunscreen agent. Such formulations may be for cosmetic or pharmaceutical purposes and may be, e.g., oil-in-water emulsions, water-in-oil emulsions, aerosols, gels, and lip balms. Such formulations may prepared by processes known per se. The formulations may, besides UV-B screening agents, contain additional UV screening agents and auxiliary agents conventionally used in topical sunscreens formulations such as emulsifiers, emollients, preservatives, fragrant etc. The invention is illustrated further by the following non-limitative examples. Example 1

Beach Care Sunscreen Cream

A Disodium EDTA 0.10 %

B Water 57.84

C Carbomer 980 0.30

D Ethylhexyl methoxycinnamate (PARSOL MCX) 7.50 lsopropyl myristate 6.00

Ethylhexyl salicylate (PARSOL EHS) 5.00 lsodecyl neopentanoate (Schercemol 105) 4.00

Benzophenone-3 (Oxybenzone) 3.00

Butyl methoxydibenzoylmethane (PARSOL 1789) 3.00

Propylene glycol dioctanate (Lexol PG800) 2.50

Potassium cetyl phosphate (Amphisol K) 2.00

Stearic acid 2.00

PVP/Eicosene copolymer (Ganex V220) 2.00

Cetyl alcohol 1.50

Dimethicone (DC 200 Fluid, 350 cs) 1.00

Tocopheryl acetate (Vitamin E Acetate) 1.00

E Triethanolamine 99% 0.90

Water 0.10

F Methyldibromo glutaronitrile (and) phenoxyethanol

(Merguard 1200) 0.15

25-Hydroxycholecalciferol 0.01

Fragrance 0.10

Procedure: Dissolve A into B. Sprinkle C into AB and mix until properly dispersed. Mix D in order. Heat ABC and D separately to 85-95°C. Add D to ABC with mixing. Using a paddle type mixer, add E to batch. Cool. At 45°C, add F to batch and mix until smooth and uniform. Example 2

Broad-Spectrum Sunscreen Lotion

A Panthenol (D-Panthenol) 0.50 %

B Water 58.21

C Carbomer 980 (Carbopol 908) 0.20

D Ethylhexyi methoxycinnamate PARSOL MCX) 7.50

Homosalate (PARSOL HMS) 6.50

Ethylhexyi salicylate (PARSOL EHS) 5.00

Benzophenone-3 (Oxybenzone) 3.00

Butyl methoxydi benzoyl methane (PARSOL 1789) 2.00

Octocrylene (PARSOL 340) 1.50 lsodecyl neopentanoate 3.00 lsopropyl myristate 3.50

Cetyl alcohol 2.00

Cetyl phosphate (Amphisol A) 1.50

PVP/Eicosene copolymer (Ganex V220) 2.00

Dimethicone ((DC 200 Fluid, 350 cs) 1.00

Tocopheryl acetate (Vitamin E Acetate) 0.50

Dimethiconol beeswax (Ultrabee) 0.25

Disodium EDTA 0.10

E Aminomethyl propanol (AMP-95) 0.55

Water 0.45

F Aluminium starch octenylsuccinate 0.50

G Methyldibromo glutaronitrile (and) phenoxyethanol

(Merguard 1200) 0.12

25-Hydroxycholecalciferol 0.02

Fragrance 0.10

Procedure: Dissolve A into B. Sprinkle C into AB and mix until properly dispersed. Heat ABC and D separately to 75°C. Add ABC to D with mixing. Using a paddle type mixer, add E to batch. Add F. Cool. At 40⁰C, add G and mix until smooth at RT.

Claims

What is claimed is :

1. The use of 25-hydroxycholecalciferol as an active ingredient in the manufacture of topical compositions which contain one or more UV-B screening agents, for the prevention of vitamin D deficiencies caused by the topical application of UV-B screening agents, and for increased skin regeneration and cosmetic treatment of skin damages caused by environmentally-induced noxious impact.

2. The use as in claim 1 wherein the deficiencies are intrinsic or extrinsic signs of skin aging, reduced activities of the skin immune system, or delayed cure of skin irritations or inflammations.

3. The use as in any one of claims 1 or 2 wherein the compositions are cosmetic compositions.

4. The use as in any one of claims 1 or 2 wherein the compositions are pharmaceutical compositions.

5. The use as in any one of claims 1 or 2 wherein the compositions are oil-in-water emulsions, water-in-oil emulsions, aerosols, gels, lip balms.

6. The use as in any one of claims 1 to 5 wherein the UV-B screening agent is Octyl Methoxycinnamate, a p-methoxy cinnamic acid derivative, 4-Methylbenzylidene camphor, Benzylidene malonate polysiloxane, Drometrizole trisiloxane, p-aminobenzoic acid or derivatives thereof, Homosalate, Octylsalicylate, Octyl Triazone, Diethylhexylbutamide Triazone, Octocrylene, 2,4,6-Tris-biphenyl-4-yl-[1 ,3,5]triazine, Bis- Ethylhexyloxyphenol Methoxyphenyl Triazine, Methylene bis-benzotriazolyl tetramethylbutylphenol, Zinc Oxide, Titanium Dioxide; or mixtures thereof.

7. The use as in any one of claims 1 to 6 wherein 25-hydroxycholecalciferol is used in an amount to provide a concentration in the composition of from about 0.0001 wt.-% to about 1 wt.-%, particularly of from about 0.001 wt.-% to about 0.1 wt.-%.

8. The use as in any one of claims 1 to 7 wherein the UV-B screening agent is present in the compositions in an amount of from about 2 wt.-% to about 40 wt.-%, particularly of from about 3 wt.-% to about 30 wt.-%

9. A method of preventing vitamin D deficiencies in a person which uses a topical composition containing a UV-B screening agent, and for increased skin regeneration and cosmetic treatment of skin damages caused by environmentally-induced noxious impact which comprises providing to that person a topical composition which contains, besides said UV-B screening agent, an effective amount of 25-hydroxycholecalciferol.

10. The method as in claim 9 wherein the deficiencies are intrinsic or extrinsic signs of skin aging, reduced activities of the skin immune system, or delayed cure of skin irritations or inflammations.

11. A method as in claim 9 or 10 wherein the effective amount of 25- hydroxycholecalciferol is from about 0.0001 wt.-% to about 1 wt.-%, particularly of from about 0.001 wt.-% to about 0.1 wt.-% based on the total weight of the composition.

12. A method as in any one of claims 9 to 11 wherein the UV-B screening agent is Octyl Methoxycinnamate, a p-methoxy-cinnamic acid derivative, 4-Methylbenzylidene Camphor, Dimethicodiethyl-Benzalmalonate, p-aminobenzoic acid or derivatives thereof, Homosalate, Octylsalicylate, Octyl Triazone, Diethylhexylbutamide Triazone, Octocrylene, Bis-Ethylhexyloxyphenol Methoxyphenyl Triazine, Methylene bis- benzotriazolyl tetramethylbutylphenol, Zinc Oxide, Titanium Dioxide; or mixtures thereof.