WO2003101415A1

WO2003101415A1 - Compositions comprisins vitamin k

Info

Publication number: WO2003101415A1
Application number: PCT/GB2003/002337
Authority: WO
Inventors: Christopher Francis Smith
Original assignee: The Boots Company Plc
Priority date: 2002-06-01
Filing date: 2003-05-30
Publication date: 2003-12-11
Also published as: AU2003240058A1; GB0212749D0

Abstract

In a composition comprising, as active ingredient, vitamin K, the vitamin K is present as a complex with a cyclodextrin. The cyclodextrin is most preferably β-cyclodextrin and the vitamin K is most preferably vitamin K1. The composition may have a generally beneficial effect on the skin, either in a therapeutic or merely cosmetic sense, e.g. in the improving the appearance of the skin or the treatment of bruising and other skin conditions associated with deposition of discolouring material beneath the skin. One particular use of the composition is for improving the appearance of the skin around the eyes, in particular a method for the cosmetic treatment of dark areas ('shadows') in the vicinity of the eyes.

Description

Title -Compositions Comprising Vitamin K

This invention relates to compositions comprising vitamin K.

Vitamin K is believed to have beneficial effects on the circulation of blood, particularly in relation to fine blood vessels (capillaries) located close to the skin. As such, vitamin K is believed to have beneficial cosmetic and/or therapeutic properties inter alia in relation to the treatment of bruising and also the diminution of unsightly features such as shadows that commonly form under the eyes. Such shadows are often associated with fatigue and/or stress. Physiologically, they are believed to be caused by the pooling of lymph fluids or red blood cells and/or the deposition of melanin-type pigments.

A problem that has hitherto been encountered with formulations of vitamin K is a lack of stability of the active ingredient (ie the vitamin K itself). This obviously leads to a loss of efficacy over a protracted period, eg in the period between manufacture and sale, and/or the period over which the product is consumed. Even where the Vitamin K is stable up to the point at which it is administered, it may be the case that the Vitamin K then breaks down relatively rapidly. This may be a particular problem for formulations that are administered orally, as they may be rapidly broken down in the stomach, with the result that the Vitamin K does not survive and pass into the duodenum, the absorption of the Vitamin K into the bloodstream being correspondingly poor.

There has now been devised an improved formulation comprising vitamin K which overcomes or substantially mitigates the above-mentioned and/or other disadvantages of the prior art.

According to the invention, there is provided a composition comprising, as active ingredient, vitamin K, wherein the vitamin K is present as a complex with a cyclodextrin.

The cyclodextrin with which the vitamin K is complexed is most preferably a naturally occurring cyclodextrin. The naturally occurring cyclodextrins consist of six, seven or eight (respectively α-, β- and γ-cyclodextrin) D-glucopyranosyl units connected by α-(1 ,4)-glycosidic linkages. The most stable three-dimensional molecular configuration for these non-reducing cyclic oligosaccharides takes the form of a toroid with the upper (larger) and lower (smaller) opening of the toroid presenting respectively secondary and primary hydroxyl groups to the solvent environment. The interior of the toroid is hydrophobic, and formation of the complex between the vitamin K and the cyclodextrin is believed to involve entry of the vitamin K molecule into the cavity in the centre of the toroidal cyclodextrin structure.

β-cyclodextrin is particularly preferred for use in the invention.

As an alternative to a naturally-occurring cyclodextrin, the cyclodextrin may be a chemically modified cyclodextrin. Examples of such chemically modified cyclodextrins include methyl cyclodextrins, hydroxyethyl cyclodextrins, hydroxypropyl cyclodextrins, glucosyl cyclodextrins, maltosyl cyclodextrins, carboxymethyl cyclodextrins and carboxyethyl cyclodextrins.

The cyclodextrin preferably comprises seven glucopyranosyl monomer units, or chemically modified glucopyranosyl monomer units.

The vitamin K may be complexed with mixtures of cyclodextrins, either naturally occurring or chemically modified.

Vitamin K is a generic name for any of several fat-soluble naphthoquinone compounds present in the leaves of plants. The preferred vitamin K compound for use in the present invention is vitamin K1 , also known as "phytonadione".

Mixtures of vitamin K compounds may be used, but it is strongly preferred that vitamin K1 should be present, most preferably as the predominant component (ie greater than 50% w/w of the mixture).

The complex may be prepared by adding the cyclodextrin to a solution or dispersion of the vitamin K in a solvent, or vice versa. The mixture is preferably agitated, eg by stirring, if necessary for a protracted period, in order to allow complete complexation. It may be desirable for the solution temperature to be lowered, eg to between 4 and 10°C. After mixing and complexation, the solvent is preferably removed, eg under vacuum. Again, the mixture is preferably continuously agitated during solvent removal.

The solvent used for complexation is preferably a polar solvent, most commonly water. Alternative solvents include alcohols, eg methanol.

The compositions of the present invention may be formulated in numerous ways, including a variety of generally conventional formulation types. The composition may, for instance, be formulated as an emulsion, a gel, a surfactant system, aqueous or oily solutions or dispersions in the conventional way. Particularly preferred topical formulations are emulsions and gels. An emulsion may be an oil- in-water emulsion or a water-in-oil emulsion. The compositions of the invention may also be formulated for oral administration, eg as tablets, capsules, or syrups.

The oil phase of the water-in-oil or oil-in-water emulsions of the present invention may comprise for example:

a) hydrocarbon oils such as paraffin or mineral oils; b) waxes such as beeswax or paraffin wax; c) natural oils such as sunflower oil, apricot kernel oil, shea butter or jojoba oil; d) silicone oils such as dimethicone, cyclomethicone or cetyl dimethicone, and silicone elastomers; e) fatty acid esters such as isopropyl palmitate, isopropyl myristate or dioctyl maleate; f) fatty alcohols such as cetyl alcohol or stearyl alcohol; or g) mixtures thereof, for example, the blend of waxes available commercially under the trade name Cutina (Henkel). In preferred water-in-oil compositions of the present invention the oil phase comprises 5 to 40%, more preferably 10 to 30% by weight of the composition. In preferred oil-in-water compositions of the present invention the oil phase comprises 5 to 30%, more preferably 10 to 20% by weight of the composition.

The emulsifiers used may be any emulsifiers known in the art for use in water-in-oil or oil-in-water emulsions. It has been found that particularly effective water-in-oil and oil-in-water compositions can be prepared by using an emulsifier or mixture of emulsifiers selected from known cosmetically acceptable emulsifiers which include:

a) sesquioleates such as sorbitan sesquioleate, available commercially for example under the trade name Arlacel 83 (ICI), or polyglyceryl-2- sesquioleate; b) ethoxylated esters of derivatives of natural oils such as the polyethoxylated ester of hydrogenated castor oil available commercially for example under the trade name Arlacel 989 (ICI); c) silicone emulsifiers such as silicone polyols available commercially for example under the trade name ABIL WS08 (Th. Goldschmidt AG); d) anionic emulsifiers such as fatty acid soaps e.g. potassium stearate and fatty acid sulphates e.g. sodium cetostearyl sulphate available commercially under the trade name Dehydag (Henkel); e) ethoxylated fatty alcohols, for example the emulsifiers available commercially under the trade name Brij (ICI); f) sorbitan esters, for example the emulsifiers available commercially under the trade name Span (ICI); g) ethoxylated sorbitan esters, for example the emulsifiers available commercially under the trade name Tween (ICI); h) ethoxylated fatty acid esters such as ethoxylated stearates, for example the emulsifiers available commercially under the trade name Myrj (ICI); i) ethoxylated mono-, di-, and tri-glycerides, for example the emulsifiers available commercially under the trade name Labrafil (Alfa Chem.); j) non-ionic self-emulsifying waxes, for example the wax available commercially under the trade name Polawax (Croda); k) ethoxylated fatty acids, for example, the emulsifiers available commercially under the trade name Tefose (Alfa Chem.); I) methylglucose esters such as polyglycerol-3 methyl glucose distearate available commercially under the name Tegocare 450 ( Degussa

Goldschmidt); or m) mixtures thereof.

The amount of emulsifier present in the emulsion compositions of the present invention is preferably in the range 1 to 10%.

The compositions of the present invention may additionally comprise other components which will be well known to those skilled in the art. These include, for example, emollients such as isopropyl myristate or triglycerides of fatty acids e.g. lauric triglyceride or capric/capr lic triglyceride, such as the triglyceride available commercially under the trade name Miglyol 810 (Huls UK); moisturisers such as D-panthenol; humectants such as glycerin or 1 ,3-butylene glycol; antioxidants such as DL-α-tocopherylacetate or butylated hydroxytoluene; emulsion stabilising salts such as sodium chloride, sodium citrate or magnesium sulphate; film formers to assist spreading on the surface of the skin such as alkylated polyvinylpyrrolidone, e.g. those available commercially under the trade name Antaron (GAF); thickeners such as acrylic acid polymers, e.g. those available commercially under the trade name Carbopol (B.F. Goodrich) or modified celluloses, e.g. hydroxyethylcellulose available commercially under the trade name Natrosol (Hercules) or alkylgalactomanans available under the trade name N-Hance; preservatives such as bronopol, sodium dehydroacetate, polyhexamethylenebiguanide hydrochloride, isothiazolone or diazolidinylurea; sequestering agents such as EDTA salts; perfumes and colourings.

The compositions of the present invention are advantageous primarily in that complexation of the vitamin K with the cyclodextrin stabilizes the vitamin K. The concentration of vitamin K in the composition is thus maintained at the desired level for a protracted period, avoiding or minimising any diminution in the efficacy of the composition over time. The complexation of the vitamin K may also lead to a sustained release of the vitamin K from the composition after its application to a user's skin. When administered orally, the vitamin K may better survive passage through the stomach into the duodenum, hence leading to improved absorbance into the bloodstream. The compositions may be effective in the treatment of bruising, and other skin conditions associated with deposition of discolouring material beneath the skin. The formulations may also have a generally beneficial effect on the skin, either in a therapeutic or merely cosmetic sense. The compositions may also be beneficial in the treatment of thread veins and chilblains. The compositions may also be of benefit in the treatment of dermatological conditions associated with dry, cracked or scaly skin, eg psoriasis, eczema and ichthyosis.

While certain uses of the compositions according to the invention may be of a therapeutic nature, others may be purely cosmetic. According to a further aspect of the invention, there is therefore provided a cosmetic method for improving the appearance of the skin, which method comprises applying to the skin a composition comprising, as active ingredient, vitamin K, wherein the vitamin K is present as a complex with a cyclodextrin.

A particular method as defined in the preceding paragraph may be a method for improving the appearance of the skin around the eyes, in particular a method for the cosmetic treatment of dark areas ("shadows") in the vicinity of the eyes.

In another aspect of the invention, there is provided a method for the treatment of a condition selected from the group consisting of bruising, thread veins, chilblains, dry skin, cracked skin, scaly skin, psoriasis, eczema and ichthyosis, which method comprises administration of vitamin K to a patient suffering from, or susceptible to, such a condition, wherein the vitamin K is in the form of a complex with a cyclodextrin.

In a related aspect, the invention provides the use of vitamin K in the form of a complex with a cyclodextrin in the manufacture of a medicament for the treatment of a condition selected from the group consisting of bruising, thread veins, chilblains, dry skin, cracked skin, scaly skin, psoriasis, eczema and ichthyosis.

The invention will now be described in greater detail with reference to the following Examples, in which the term "Vitamin K Complex" refers to a complex of vitamin K1 with β-cyclodextrin containing 10% w/w vitamin K, and prepared as follows:

Process for Vitamin K Complex production

1. Melt and mix the quantity of vitamin K in an appropriate solvent.

2. Mix with β-cyclodextrin considering only the relation between the vitamin K and the cyclodextrin (ie disregarding the solvent, which will be subsequently removed, and to ensure that the final concentration of vitamin K is as desired). 3. Under vacuum eliminate the solvent at a temperature between 4-10°C, stirring the product continuously. 4. Maintain under a reduced or inert atmosphere for about 24 hours before emptying.

Example 1 - Aftersun Lotion

%w/w

Aqua to 100

Hydrated silica 5

Isopropyl palmitate 4 Arachidyl propionate 2

Dimethicone 2

Glycerin 2

Steareth-21 1.96

Steareth-2 1.683 Cetyl alcohol 1

Tribehenin 1

Glyceryl stearate 1 Paraffinum liquidum 0.994

Panthenol 0.75

Parfum 0.3

Xanthan gum 0.3 Sodium citrate 0.25

Tocopheryl acetate 0.2

Hydroxyethylcellulose 0.1

Bisabolol 0.095

Citric acid 0.05 Preservative q.s

Vitamin K Complex 1

Method

Stage 1

The citric acid, sodium citrate and hydroxyethylcellulose are added to the water. Using a propellor stirrer, the mixture is stirred until dispersed. The xanthan gum is pre-dispersed in the glycerin and this is then added to the bulk, which is then heated to 70°C.

Stage 2

The isopropyl palmitate, arachidyl propionate, dimethicone, steareth-21, steareth- 2, cetyl alcohol, tribehenin, glyceryl stearate, paraffinum liquidum are mixed and heated to 70°C to melt the waxes.

Stage 3

Using a homogeniser, stage 2 is added to stage 1 and is mixed until emulsified and uniform. The emulsion is cooled to below 35° C using stirring. Once below 35°C, the remaining materials are added, including the Vitamin K Complex. The product is made to weight using purified water, and mixed until uniform.

Example 2 - Aftersun Lotion

%w/w Aqua to 100

Hydrated silica 5

Isopropyl palmitate 4

Arachidyl propionate 2 Dimethicone 2

Glycerin 2

Steareth-21 1.96

Steareth-2 1.683

Cetyl alcohol 1 Tribehenin 1

Glyceryl stearate 1

Paraffinum liquidum 0.994

Panthenol 0.75

Parfum 0.3 Xanthan gum 0.3

Sodium citrate 0.25

Tocopheryl acetate 0.2

Hydroxyethylcellulose 0.1

Bisabolol 0.095 Citric acid 0.05

Preservative q.s

Vitamin K Complex 10

Method

Stage 1

Stage 2

The isopropyl palmitate, arachidyl propionate, dimethicone, steareth-21 , steareth- 2, cetyl alcohol, tribehenin , glyceryl stearate, paraffinum liquidum are mixed and heated to 70°C to melt the waxes.

Stage 3 Using a homogeniser, stage 2 is added to stage 1 and is mixed until emulsified and uniform. The emulsion is cooled to below 35° C using stirring. Once below 35°C, the remaining materials are added, including the Vitamin K Complex. The product is made to weight using purified water, and mixed until uniform.

Example 3 - Day Cream

%w/w

Aqua to 100

Butylene glycol 5

Dicaprylyl maleate 4

Paraffinum liquidum 4

Octyl methoxycinnamate 3

Petrolatum 3

Cetyl Alcohol 2

Glycerin 2

Dimethicone 2

Cetearyl alcohol 1.6

Butyl methoxydibenzoylmethane 1

Hydroxyethylcellulose 0.4

PEG-20 stearate 0.4

Polyacrylamide 0.4

Parfum 0.3

C13-14 isoparaffin 0.215

Retinyl palmitate 0.15

Tetrasodium EDTA 0.1

Citric acid 0.08

Laureth-7 0.055

BHT 0.0024

Vitamin K Complex 1 Preservative q.s

Method

Stage 1

Tetrasodium EDTA and citric acid are added to the water using a propellor stirrer.

The hydroxyethylcellulose is added and dispersed using a homogeniser. butylene glycol, glycerin and methylparaben are added and the bulk is heated to

70°C.

Stage 2

The dicaprylyl maleate, paraffinum liquidum, octyl methoxycinnamate, petrolatum, cetyl alcohol, dimethicone, cetearyl alcohol, butyl methoxydibenzoylmethane, PEG-20 stearate, C13-14 isoparaffin, laureth-7 and BHT are mixed and heated to 70°C to melt the waxes.

Stage 3

Using a homogeniser, stage 2 is added to stage 1 and the bulk is mixed until emulsified and stable. The product is then cooled to below 35°C using stirring. The remaining raw materials, including the Vitamin K Complex are added and the product is mixed using a propellor stirrer until uniform. The product is made to weight using purified water.

Example 4 - Day Cream %w/w

Aqua to 100

Butylene glycol 5

Dicaprylyl maleate 4

Paraffinum liquidum 4 Octyl methoxycinnamate 3

Petrolatum 3

Cetyl Alcohol 2

Glycerin 2 Dimethicone 2

Cetearyl alcohol 1.6

Butyl methoxydibenzoylmethane 1

Hydroxyethylcellulose 0.4

PEG-20 stearate 0.4

Polyacrylamide 0.4

Parfum 0.3

C13-14 isoparaffin 0.215

Retinyl palmitate 0.1782

Tetrasodium EDTA 0.1

Citric acid 0.08

Laureth-7 0.055

BHT 0.0024

Vitamin K Complex 10

Preservative q.s

Method

Stage 1 Tetrasodium EDTA and citric acid are added to the water using a propellor stirrer. The hydroxyethylcellulose is added and dispersed using a homogeniser. butylene glycol, glycerin and methylparaben are added and the bulk is heated to 70°C.

Stage 2

Stage 3

Example 5 - Sun Lotion SPF8

%w/w

Aqua to 100

C12-15 Alkyl Benzoate 8

Butylene glycol 5 Butyl methoxydibenzoylmethane 2.2

Dimethicone 2

Polyglyceryl-3 methylglucose distearate 2

PVP/hexadecene copolymer 1.75

Octyl methoxycinnamate 1.7 Theobroma cacao 0.5

Parfum 0.5

Tocopheryl acetate 0.2

Acrylates/vinyl isodecanoate crosspolymer 0.15

Potassium hydroxide 0.034 Tetrasodium EDTA 0.02

Preservative q.s

Vitamin K Complex 1

Method

Stage 1

The EDTA is dispersed into the water. Using a propellor stirrer, the acrylates/vinyl isodecanoate crosspolymer are added and dispersed and hydrated. Butylene glycol is added and the aqueous phase is heated to 70°C.

Stage 2

The C12-15 alkyl benzoate, butyl methoxydibenzoylmethane, dimethicone, polyglyceryl-3 methylglucose distearate, PVP/hexadecene copolymer, octyl methoxycinnamate, theobroma cacao and tocopheryl acetate are mixed and heated to 70°C to melt the waxes.

Stage 3 Using a homogeniser, stage 2 is added to stage 1 and the bulk is mixed until emulsified and uniform. The emulsion is cooled to below 35°C with stirring. The remaining materials, including the Vitamin K Complex are added and mixed. The product is made to weight using purified water and stirred until uniform.

Example 6 - Sun Lotion SPF8

%w/w

Aqua to 100

C12-15 Alkyl Benzoate 8

Butylene glycol 5 Butyl methoxydibenzoylmethane 2.2

Dimethicone 2

Polyglyceryl-3 methylglucose distearate 2

PVP/hexadecene copolymer 1.75

Octyl methoxycinnamate 1.7 Theobroma cacao 0.5

Parfum 0.5

Tocopheryl acetate 0.2

Acrylates/vinyl isodecanoate crosspolymer 0.15

Potassium hydroxide 0.034 Tetrasodium EDTA 0.02

Preservative q.s

Vitamin K Complex 10

Method

Stage 1

Stage 2

Example 7 - Sunburn Treatment

%w/w

Aqua to 100

Petrolatum 3

Cetyl Alcohol 2 Dimethicone 2

Glycerin 2

Ceteath-20 1.7

Paraffinum Liquidum 1

Sodium chloride 0.8 Theobroma cacao 0.7

Glyceryl stearate 0.5

Parfum 0.3

Allantoin 0.2

Hydroxyethylcellulose 0.1 Triclosan 0.1

Citric acid 0.02

Preservative q.s

Vitamin K Complex 1 Method

Stage 1 Into the water, sodium chloride and citric acid are added and dispersed. Using a propellor stirrer, hydroxyethylcellulose is added and dispersed. This phase is then heated to 70°C.

Stage 2 The petrolatum, cetyl alcohol, dimethicone, ceteath-20, paraffinum liquidum, theobroma cacao and glyceryl stearate are mixed and heated to 70°C to melt the waxes.

Stage 3 Using a homogeniser, stage 2 is added to stage 1, this is mixed until emulsified and uniform. The emulsion is then cooled to below 35°C with stirring. The remaining materials, including the Vitamin K Complex are then added and mixed. The product is made to weight using purified water and stirred until uniform.

Example 8 - Sunburn Treatment

%w/w

Aqua to 100

Petrolatum 3

Cetyl Alcohol 2 Dimethicone 2

Glycerin 2

Ceteath-20 1.7

Paraffinum Liquidum 1

Sodium chloride 0.8 Theobroma cacao 0.7

Glyceryl stearate 0.5

Parfum 0.3

Allantoin 0.2 Hydroxyethylcellulose 0.1

Triclosan 0.1

Citric acid 0.02

Preservative q.s Vitamin K Complex 10

Method

Stage 3 Using a homogeniser, stage 2 is added to stage 1 , this is mixed until emulsified and uniform. The emulsion is then cooled to below 35°C with stirring. The remaining materials, including the Vitamin K Complex are then added and mixed. The product is made to weight using purified water and stirred until uniform.

Example 9 - Eve Cream

%w/w

Aqua to 100

Butylene glycol 6

Paraffinum liquidum 5 Octyl methoxycinnamate 4

Dimethicone 2

Petrolutum 2

Cetearyl octanoate 1.8 Cetearyl alcohol 1.6

Glyceryl stearate 1.5

Cetyl alcohol 1

Prunus dulcis 1

Glycerin 0.57

Hydrogenated vegetable glycerides citrate 0.5

Tocopheryl acetate 0.5

Bisabolol 0.475

Panthenol 0.45

Sodium phosphate 0.42

PEG-20 stearate' 0.4

Isopropyl myristate 0.2

Carbomer 0.15

PEG-12 isostearate 0.125

Allantoin 0.1

Tetrasodium EDTA 0.1

Lactic acid 0.088

Disodium phophate 0.083

Potassium hydroxide 0.051

Vitamin K Complex 1

Preservative q.s

Method

Stage 1

Into the water, citric acid, EDTA, sodium phosphate, disodium phosphate and lactic acid are added and dispersed. Using a homogeniser, carbomer is added and hydrated. The aqueous phase is then heated to 70°C.

Stage 2

The paraffinum liquidum, octyl methoxycinnamate, dimethicone, petrolatum, cetearyl octanoate, cetearyl alcohol, glyceryl stearate, cetyl alcohol, hydrogenated vegetable glycerides citrate, tocopheryl acetate, PEG-20 stearate, isopropyl myristate and PEG-12 isostearate are mixed and heated to 70°Cto melt the waxes.

Stage 3

Using a homogeniser, stage 2 is added to stage 1 and this is mixed until emulsified and uniform. The emulsion is then cooled to below 35°C using stirring.

The remaining materials, including the Vitamin K Complex are then added and mixed. The product is then made to weight using purified water and is stirred until uniform.

Example 10 - Eve Cream

%w/w

Aqua to 100

Butylene glycol 6

Paraffinum liquidum 5

Octyl methoxycinnamate 4

Dimethicone 2

Petrolutum 2

Cetearyl octanoate 1.8

Cetearyl alcohol 1.6

Glyceryl stearate 1.5

Cetyl alcohol 1

Prunus dulcis 1

Glycerin 0.57

Hydrogenated vegetable glycerides citrate 0.5

Tocopheryl acetate 0.5

Bisabolol 0.475

Panthenol 0.45

Sodium phosphate 0.42

PEG-20 stearate 0.4

Isopropyl myristate 0.2

Carbomer 0.15

PEG-12 isostearate 0.125 Allantoin 0.1

Tetrasodium EDTA 0.1

Lactic acid 0.088

Disodium phophate 0.083

Potassium hydroxide 0.051

Vitamin K Complex 10

Preservative q.s

Method

Stage 1

Stage 2

Stage 3

Using a homogeniser, stage 2 is added to stage 1 and this is mixed until emulsified and uniform. The emulsion is then cooled to below 35°C using stirring. The remaining materials, including the Vitamin K Complex are then added and mixed. The product is then made to weight using purified water and is stirred until uniform.

Example 11 - Eve Gel

%w/w Aqua to 100

PVP/VA copolymer 2 Propylene glycol 2

Carbomer 1

PEG-40 hydrogenated castor oil 1

Panthenol 1 Sodium hydroxide 0.3

Phenoxyethanol 0.2

Tetrasodium EDTA 0.1

Vitamin K Complex 1

Method

Stage 1

The EDTA, Methyldibromo glutaronitrile, PVP/VA copolymer and Carbomer were added to the water and mixed using a homogeniser to ensure that the polymers were hydrated.

Stage 2

With continued homogenising, the Cystine hydroxypropyl polysiloxane was added and mixed into the product.

Stage 3

The remaining materials, including the Vitamin K Complex were added individually and mixed using a prop. Strirrer until the product was homogenous.

Example 12 - Refreshing cream

%w/w

Aqua to 100

Butylene glycol 7.5

Silica 7.2 Arabinogalactan 5.35

Dimethicone 5.35

Petrolatum 5.35

Hydrated silica 3.75 Steareth-2 2.7

Prunus dulcis 2.7

Steareth-21 0.9

PVP/hexadecene copolymer 0.8 Carbomer 0.32

Sodium PCA 0.2

Parfum 0.2

Hydroxyethylcellulose 0.16

Potassium hydroxide 0.1 Propylene glycol 0.1

Vitamin K Complex 1

Preservative q.s

Method

Stage 1

Into the water, the carbomer is added and hydrated using a homogeniser. The aqueous phase is then heated to 70°C.

Stage 2

The silica, arabinogalactan, PVP/hexadecene copolymer, dimethicone, petrolatum, hydrated silica, steareth-2 and steareth-21 are mixed and heated to 70°C to melt the waxes.

Stage 3

Example 13 - Skin Protection Lotion

%w/w Aqua to 100

Dimethicone 5

Glycerin 3

Kaolin 3

Dicaprylyl maleate 2.5

Isopropyl myristate 2.5

Stearate-2 2

Octyl methoxycinnamate 1

Steareth-21 1

Cetyl alcohol 0.75

Butyl methoxydibenzoylmethane 0.5

Propylene glycol 0.5

Hydroxyethylcellulose 0.4

Xanthan gum 0.24

Serica 0.1

Sodium C8-16 isoalkylsuccinyl lactoglobulin sulfonate 0.1

Tetrasodium EDTA 0.1

Citric acid 0.05

Vitamin K Complex 1

Preservative q.s

Method

Stage 1 Into the water, the citric acid and EDTA are added and dispersed. The hydroxyethylcellulose is added and hydrated using a propellor stirrer. Xanthan gum is pre-dispersed in glycerin and added to the bulk. This is stirred until uniform. The aqueous phase is then heated to 70°C.

Stage 2

The dimethicone, dicaprylyl maleate, isopropyl myristate, stearate-2, octyl methoxycinnamate, steareth-21 , cetyl alcohol and butyl methoxydibenzoylmethane are mixed and heated to 70 °C to melt the waxes. Stage 3

Example 14 - Night Cream %w/w

Aqua to 100

Glycerin 5

Paraffinum liquidum 4.5

Dicaprylyl maleate 3 Dimethicone 3

Petrolatum 3

Paraffin 2.9

Cetyl alcohol 2

Steareth-2 2 Glyceryl stearate 1.5

Butyrospermum parkii 1.5

Steareth-21 1

Mannitol 1

Cera microcristallina 0.262 Buxus chinensis 0.5

Propylene glycol 0.48

Parfum 0.4

Borago officinalis 0.3

Hydroxyethylcellulose 0.3 Lactis proteinum 0.3

Xanthan gum 0.25

Alcohol denat. 0.08

Sodium citrate 0.08 Lecithin 0.075

BHT 0.05

Faex 0.04

Phospholipids 0.03

Citric acid 0.025

Vitamin K Complex 1

Preservative q.s

Method

Stage 1

Into the water, the citric acid and sodium citrate are added and dispersed. The hydroxyethylcellulose is added and hydrated using a propellor stirrer. Xanthan gum is pre-dispersed in glycerin and added to the bulk. This is stirred until uniform. The aqueous phase is then heated to 70°C.

Stage 2

The paraffinum liquidum, dicaprylyl maleate, dimethicone, petrolatum, paraffin, cetyl alcohol, steareth-2, glyceryl stearate, steareth-21, cera microcristallina and BHT are mixed and heated to 70°C to melt the waxes.

Stage 3

Example 15 - Sun Lotion for Sensitive Skin - SPF15 %w/w

Aqua to 100

C12-15 alkyl benzoate 12

Butylene glycol 5 Octyl methoxycinnamate 3.8

Butyl methoxydibenzoylmethane 3

Dimethicone 2

Polyglyceryl-3 methylglucose distearate 2 PVP/hexadecene copolymer 1.75

C18-36 acid glycol ester 1.5

Polysorbate 60 0.5

Titanium dioxide 0.3

Tocopheryl acetate 0.2 Acrylates/vinyl isodecanoate crosspolymer 0.14

Potassium hydroxide 0.035

Tetrasodium EDTA 0.02

Preservative q.s

Vitamin K Complex 1

Method

Stage 1

Into the water, citric acid is added and dispersed. The acrlyates/vinyl isodecanoate crosspolymer are added and dispersed using a propellor stirrer. The aqueous phase is then heated to 70°C.

Stage 2

The C12-15 alkyl benzoate, PVP/hexadecene copolymer, octyl methoxycinnamate, butyl methoxydibenzoylmethane, dimethicone, polyglyceryl-3 methylglucose distearate, C18-36 acid glycol ester, polysorbate 60, titanium dioxide and tocopheryl acetate are mixed and heated to 70°C to melt the waxes.

Stage 3 Using a homogeniser, stage 2 is added to stage 1 and this is mixed until emulsified and uniform. The emulsion is then cooled to below 35°C using stirring. The remaining materials, including the Vitamin K Complex are then added and mixed. The product is then made to weight using purified water and is stirred until uniform.

Example 16 - Sun Lotion for Sensitive Skin - SPF15

%w/w Aqua to 100

C12-15 alkyl benzoate 12

Butylene glycol 5

Octyl methoxycinnamate 3.8

Butyl methoxydibenzoylmethane 3 Dimethicone 2

Polyglyceryl-3 methylglucose distearate 2

PVP/hexadecene copolymer 1.75

C18-36 acid glycol ester 1.5

Polysorbate 60 0.5 Titanium dioxide 0.3

Tocopheryl acetate 0.2

Acrylates/vinyl isodecanoate crosspolymer 0.14

Potassium hydroxide 0.035

Tetrasodium EDTA 0.02 Preservative q.s

Vitamin K Complex 10

Method

Stage 1

Into the water, citric acid is added and dispersed. The acrylates/vinyl isodecanoate crosspolymer are added and dispersed using a propellor stirrer. The aqueous phase is then heated to 70°C.

Stage 2

The C12-15 alkyl benzoate, PVP/hexadecene copolymer, octyl methoxycinnamate, butyl methoxydibenzoylmethane, dimethicone, polyglyceryl-3 methylglucose distearate, C18-36 acid glycol ester, polysorbate 60, titanium dioxide and tocopheryl acetate are heated to 70°C to melt the waxes.

Stage 3

Example 17 - Sun Cream For Sensitive Skin

%w/w

Aqua to 100

Octyl stearate 13.5

Zinc oxide 13.5 Isopropyl myristate 5

Butylene glycol 3

Isohexadecane 3

Titanium dioxide 2

Polyglyceryl-3 oleate 1.75 Cetyl dimethicone copolyol 1.35

Magnesium sulfate 0.75

Sodium chloride 0.75

Aluminium stearate 0.18

Alumina 0.15 Lecithin 0.13

Isopropyl palmitate 0.05

Vitamin K Complex 1

Method

Stage 1

Into the water, magnesium sulfate, sodium chloride and butylene glycol are added and dispersed. The aqueous phase is then heated to 70°C. Stage 2

The octyl stearate, isopropyl myristate, isohexadecane, titanium dioxide, polyglyceryl-3 oleate, cetyl dimethicone copolyol, aluminium stearate, lecithin and isopropyl palmitate are mixed and heated to 70°C to melt the waxes.

Stage 3

Using a propellor stirrer, stage 2 is added to stage 1. Once uniform, the emulsion is transferred to a homogeniser and mixed to generate the viscosity. The emulsion is then cooled to below 35°C using stirring. The remaining materials, including the Vitamin K Complex are then added and mixed. The product is then made to weight using purified water and is stirred until uniform.

Example 18 - Sun Cream For Sensitive Skin %w/w

Aqua to 100

Octyl stearate 13.5

Zinc oxide 13.5

Isopropyl myristate 5 Butylene glycol 3

Isohexadecane 3

Titanium dioxide 2

Polyglyceryl-3 oleate 1.75

Cetyl dimethicone copolyol 1.35 Magnesium sulfate 0.75

Sodium chloride 0.75

Aluminium stearate 0.18

Alumina 0.15

Lecithin 0.13 Isopropyl palmitate 0.05

Vitamin K Complex 10

Method Stage 1

Into the water, magnesium sulfate, sodium chloride and butylene glycol are added and dispersed. The aqueous phase is then heated to 70°C.

Stage 2

Stage 3

Example 19 - Anti-ageing Foundation

%w/w

Aqua to 100

Butylene glycol 9.8

Cetearyl isononanoate 4.9

Dimethicone 3.2

Glycerin 1.96

Silica 1.9

Caprylic/capric triglyceride 1.67

Paraffinum liquidum 1.67

Petrolatum 1.67

Hydrogenated coco-glycerides 1.67

Cetearyl octanoate 1.5

Cetearyl alcohol 1.35

Octyl methoxycinnamate 1.28

Talc 1 Glyceryl stearate 0.95

PEG-100 stearate 0.9

Butyl methoxydibenzoylmethane 0.6

Saccharide isomerate 0.54 Lactic acid 0.45

Sodium polyacrylate 0.45

Boron nitride 0.42

Sodium PCA 0.4

Borago officinalis 0.4 Tocopheryl acetate 0.4

PVP/hexadecene copolymer 0.4

PEG-20 stearate 0.33

Glycolic acid 0.2

Sodium stearoyl lactylate 0.2 Isopropyl myristate 0.17

Polyaminopropyl biguanide 0.16

Tetrasodium EDTA 0.1

Xanthan gum 0.1

Citric acid 0.06 Alcohol denat. 0.04

Lecithin 0.037

Preservative q.s

Vitamin K Complex 1

Method

Stage 1

Into the water, citric acid, EDTA and lactic acid are added and dispersed. Xanthan gum is pre-dispersed in butylene glycol and is added to the bulk. The aqueous phase is then heated to 70°C.

Stage 2

The cetearyl isononanoate, dimethicone, silica, PVP/hexadecene copolymer, caprylic/capric triglyceride, paraffinum liquidum, petrolatum, hydrogenated coco- glycerides, cetearyl octanoate, cetearyl alcohol, octyl methoxycinnamate, talc, glyceryl stearate, PEG-100 stearate, butyl methoxydibenzoylmethane, borago officinalis, tocopheryl acetate, sodium stearoyl lactylate, isopropyl myristate and lecithinoil phase are mixed and heated to 70°C to melt the waxes.

Stage 3

Example 20 - Anti-ageing Foundation

%w/w

Aqua to 100

Butylene glycol 9.8

Cetearyl isononanoate 4.9

Dimethicone 3.2

Glycerin 1.96

Silica 1.9

Caprylic/capric triglyceride 1.67

Paraffinum liquidum 1.67

Petrolatum 1.67

Hydrogenated coco-glycerides 1.67

Cetearyl octanoate 1.5

Cetearyl alcohol 1.35

Octyl methoxycinnamate 1.28

Talc 1

Glyceryl stearate 0.95

PEG-100 stearate 0.9

Butyl methoxydibenzoylmethane 0.6

Saccharide isomerate 0.54 Lactic acid 0.45

Sodium polyacrylate 0.45

Boron nitride 0.42

Sodium PCA 0.4

Borago officinalis 0.4

Tocopheryl acetate 0.4

PVP/hexadecene copolymer 0.4

PEG-20 stearate 0.33

Glycolic acid 0.2

Sodium stearoyl lactylate 0.2

Isopropyl myristate 0.17

Polyaminopropyl biguanide 0.16

Tetrasodium EDTA 0.1

Xanthan gum 0.1

Citric acid 0.06

Alcohol denat. 0.04

Lecithin 0.037

Preservative q.s

Vitamin K Complex 10

Method

Stage 1

Stage 2

Stage 3

Example 21 - Sun Sprav - SPF15

%w/w

Aqua to 100

Dicaprylyl maleate 12

Butylene glycol 5 Octyl methoxycinnamate 4

Butyl methoxydibenzoylmethane 3.5

Dimethicone 3

Polyglyceryl-3 methylglucose distearate 3

Acrylates/octylacrylamide copolymer 2 C18-36 acid glycol ester 1.5

Triethanolaraine 0.5

Tocopheryl acetate 0.2

Acrylates/vinyl isodecanoate crosspolymer 0.05

Tetrasodium EDTA 0.02 Potassium hydroxide 0.015

Preservative q.s

Vitamin K Complex 1

Method

Stage 1

Into the water, EDTA is added and dispersed. Acrylates/vinyl isodecanoate crosspolymer are added and dispersed using a propellor stirrer. Butylene glycol is added and dispersed. The aqueous phase is then heated to 70°C.

Stage 2

The dicaprylyl maleate, Acrylates/octylacrylamide copolymer, octyl methoxycinnamate, butyl methoxydibenzoylmethane, dimethicone, polyglyceryl-3 methylglucose, C18-36 acid glycol ester and tocopheryl acetate are mixed and heated to 80°C to melt the waxes.

Stage 3 Using a homogeniser, stage 2 is added to stage 1 and this is mixed until emulsified and uniform. The emulsion is then cooled to below 35°C using stirring.

Example 22 - Sun Sprav - SPF15

%w/w

Aqua to 100

Dicaprylyl maleate 12 Butylene glycol 5

Octyl methoxycinnamate 4

Butyl methoxydibenzoylmethane 3.5

Dimethicone 3

Polyglyceryl-3 methylglucose distearate 3 Acrylates/octylacrylamide copolymer 2

C18-36 acid glycol ester 1.5

Triethanolamine 0.5

Tocopheryl acetate 0.2

Acrylates/vinyl isodecanoate crosspolymer 0.05 Tetrasodium EDTA 0.02

Potassium hydroxide 0.015

Preservative q.s

Vitamin K Complex 10 Method

Stage 1 Into the water, EDTA is added and dispersed. Acrylates/vinyl isodecanoate crosspolymer are added and dispersed using a propellor stirrer. Butylene glycol is added and dispersed. The aqueous phase is then heated to 70°C.

Stage 2 The dicaprylyl maleate, Acrylates/octylacrylamide copolymer, octyl methoxycinnamate, butyl methoxydibenzoylmethane, dimethicone, polyglyceryl-3 methylglucose, C18-36 acid glycol ester and tocopheryl acetate are mixed and heated to 70°C to melt the waxes.

Stage 3

Example 23 - Toner & Cleanser 2 In 1

%w/w

Alcohol denat. 48

Aqua to 100

PEG-8 6

Glycerin 2

Propylene glycol 0.5

Sodium C8-16 isoalkylsuccinyl lactoglobulin sulfonate 0.02

Laminaria saccharina 0.01

Hamamelis virginiana 0.006

Citrullus vulgaris 0.001

Preservative q.s Vitamin K Complex 1

Method

Stage 1

Into the water, alcohol denat. Is added and dispersed until uniform. Using a propellor stirrer, all materials including the Vitamin K Complex, are slowly added and stirred until uniform. The product is made to weight using purified water and stirred until uniform.

Example 24 - Toner & Cleanser 2 In 1

%w/w

Alcohol denat. 48

Aqua to 100 PEG-8 6

Glycerin 2

Propylene glycol 0.5

Sodium C8-16 isoalkylsuccinyl lactoglobulin sulfonate 0.02

Laminaria saccharina 0.01 Hamamelis virginiana 0.006

Citrullus vulgaris 0.001

Preservative q.s

Vitamin K Complex 10

Method

Stage 1

Example 25 - Skin pH Balancing Toner %w/w

Aqua to 100

Alcohol denat. 7.9

Butylene glycol 2 Dimethicone copolyol 1.5

Sodium lactate 0.6

Glycerin 0.5

Allantoin 0.1

Propylene glycol 0.1 Lactic acid 0.002

Preservative q.s

Vitamin K Complex 1

Method

Stage 1

Into the water, lactic acid and alcohol denat are separately added and dispersed until uniform. Using a propellor stirrer, all materials including the Vitamin K Complex, are slowly added and stirred until uniform. The product is made to weight using purified water and stirred until uniform.

Example 26 - Skin pH Balancing Toner

%w/w

Aqua to 100 Alcohol denat. 7.9

Butylene glycol 2

Dimethicone copolyol 1.5

Sodium lactate 0.6

Glycerin 0.5 Allantoin 0.1

Propylene glycol 0.1

Lactic acid 0.002

Preservative q.s Vitamin K Complex 10

Method

Stage 1

Example 27 - pH Balanced Cleansing Lotion

%w/w

Aqua to 100

Paraffinum liquidum 14

Isopropyl palmitate 7

Glyceryl stearate 2.5

PEG-100 stearate 2.5

Butylene glycol 2

Hydrogenated vegetable glycerides citrate 2

Polysorbate 60 0.5

Sorbitan stearate 0.5

Persea gratissima 0.3

Prunus persica 0.3

Propylene glycol 0.3

Acrylates/C10-30 alkyl acrylate crosspolymer 0.12

Potassium hydroxide 0.05

Tetrasodium EDTA 0.02

Medicago sativa 0.0045

Preservative q.s

Vitamin K Complex 1

Method Stage 1

Into the water, EDTA is added and dispersed. Butylene glycol is then added and dispersed. The aqueous phase is then heated to 70°C.

Stage 2

The paraffinum liquidum, isopropyl palmitate, glyceryl stearate, PEG-100 stearate, hydrogenated vegetable glycerides citrate, polysorbate 60 and sorbitan stearate are mixed and heated to 70°C to melt the waxes.

Stage 3

Example 28 - pH Balanced Cleansing Lotion

%w/w

Aqua to 100 Paraffinum liquidum 14

Isopropyl palmitate 7

Glyceryl stearate 2.5

PEG-100 stearate 2.5

Butylene glycol 2 Hydrogenated vegetable glycerides citrate 2

Polysorbate 60 0.5

Sorbitan stearate 0.5

Persea gratissima 0.3

Prunus persica 0.3 Propylene glycol 0.3

Acrylates/C10-30 alkyl acrylate crosspolymer 0.12

Potassium hydroxide 0.05

Tetrasodium EDTA 0.02 Medicago sativa 0.0045

Preservative q.s

Vitamin K Complex 10

Method

Stage 1

Stage 2

Stage 3

Example 29 - Lipstick

% w/w

Ricinus communis 20

Octyldodecanol 15

Pentaerythrityl tetracaprylate/caprate 14

Mica 10

Bis-diglyceryl caprylate/caprate/isostearate/ stearate/hydroxystearate adipate 7.5

Paraffin 5

Cera microcristallina 5

Propylene glycol 2 Hydrogenated castor oil 2

Candelilla cera 1

Camauba 1

Synthetic wax 1 Butyrospermum parkii 1

Titanium dioxide 0.5

Tocopheryl acetate 0.2

Polyquaternium-37 0.2

Red colour q.s Vitamin K Complex 1

Method

Stage 1 The Vitamin K Complex is pre-dispersed in propylene glycol, with stirring.

Stage 2

The remaining materials are mixed in a vessel and heated to 85°C until melted and uniform. The product is cooled and the Vitamin K Complex pre-mix is added below 70°C. The product poured into a suitable container and allowed to cool to room temperature to set.

Example 30 - Lipstick

% w/w

Ricinus communis 20

Octyldodecanol 15

Pentaerythrityl tetracaprylate/caprate 14

Mica 10

Paraffin 5

Cera microcristallina 5

Propylene glycol 2 Hydrogenated castor oil 2 Candelilla cera 1 Camauba 1 Synthetic wax 1 Butyrospermum parkii 1 Titanium dioxide 0.5 Tocopheryl acetate 0.2 Polyquatemium-37 0.2 Red colour q.s Vitamin K Complex 10

Method

Stage 2

Example 31 - Hair Conditioner

%w/w Aqua to 100

Cetyl alcohol 3

Cetrimonium chloride 0.8

Hydroxyethylcellulose 0.6

Propylene glycol 0.5 Panthenol 0.5

Parfum 0.3

Benzophenone-4 0.2

Sodium chloride 0.1 Wheat amino acids 0.14

Citric acid 0.02

Tetrasodium EDTA 0.02

Vitamin K Complex 1

Method

Stage 1

The EDTA and Hydroxyethylcellulose were added to the water and mixed using a homogeniser to hydrate the polymer. Citric acid, Benzophenone and Cetrimonium chloride were added. This was then heated to 70C.

Stage 2

Cetyl alcohol was heated to 70C in a separate vessel.

Stage 3

The melted Cetyl alcohol was then added to stage 1 using a homogeniser.

Stage 4 The mixture was then cooled to below 40C using a propellor stirrer. The remaining materials including the Vitamin K Complex were then added and the product was made to weight with purified water.

Example 32 - Intensive Conditioner %w/w

Aqua to 100

Cetearyl alcohol 4.5

Arachidyl propionate 2

Dimethicone 2 Panthenol 0.75

Stearamidopropyl dimethylamine 1.5

Hydroxyethylcellulose 0.5

Amodimethicone 0.7 Citric acid 0.5

Cetrimonium chloride 0.4

PEG-20 stearate 0.4

Parfum 0.3 Propylene glycol 0.3

Benzophenone-4 0.2

Sodium chloride 0.15

Wheat amino acids 0.15

Polyquaternium-39 0.1 Vitamin K Complex 1

Method

Stage 1 The EDTA and HEC were added to the water and mixed using a homogeniser to hydrate the polymer.

Stage 2

The citric acid and cetrimonium chloride were added and mixed using a propellor stirrer. The mixture was then heated to 70°C.

Stage 3

In a separate vessel, the waxes, dimethicone and BHT were mixed and heated to 70°C until melted and uniform.

Stage 4

Stage 3 was added to stage 2 and this was mixed until uniform. The mixture was then cooled to below 40°C with stirring.

Stage 5

The remaining materials including the Vitamin K Complex were then added and the product was made to weight using purified water. Example 33 - Leave-in Conditioner

%w/w

Aqua to 100

PEG-40 hydrogenated castor oil 2 Dipropylene glycol 1

Phenoxyethanol 0.8

Parfum 0.3

Panthenol 0.4

Propylene glycol 0.25 Methylparaben 0.2

Benzophenone-4 0.2

Vitamin K Complex 1

Method

Stage 1

The Polyquaternium-10 was added to the water and hydrated using a propellor stirrer.

Stage 2

The Methylparaben was pre-dispersed in Dipropylene glycol, gently heated to melt and then added to stage 1.

Stage 3 The remaining materials including the Vitamin K Complex were then added and the product was mixed and made to weight with purified water.

Example 34 - Gentle Shampoo

%w/w Aqua to 100

Sodium laureth sulfate 8

Cocamidopropyl betaine 3

Sodium chloride 1.8 Cocamide DEA 1.6

PEG-6 cocamide 1

Parfum 0.5

Panthenol 0.4

Propylene glycol 0.3

Benzophenone-4 0.2

Glycerin 0.2

Phenoxyethanol 0.1

Vitamin K Complex 1

Method

Stage 1

To the water, EDTA, Sodium chloride, Citric acid and Benzophenone-4 were added. This was followed by the addition of Sodium laureth sulfate, methyldibromo glutaronitrile, wheat amino acids and the Vitamin K Complex.

Stage 2

PEG-6 cocamide and Cocamide DEA were heated gently until liquified. The parfume was added and mixed. This was then added to the product.

Stage 3

The Cocamidopropyl betaine and remaining materials, including the Vitamin K

Complex were then added and mixed. The product was made to weight using purified water.

Example 35 - Intensive Conditioner

%w/w

Aqua to 100 Sodium laureth sulfate 8.5

Cocamidopropyl betaine 23

Cocamide DEA 2.2

Panthenol 1 Sodium chloride 0.8

Laureth-3 0.5

Parfum 0.3

Propylene glycol 0.5

Benzophenone-4 0.2

Glycerin 0.5

Phenoxyethanol 0.5

Vitamin K Complex 1

Example 36 - Anti-dandruff Shampoo

%w/w

Aqua to 100

Sodium laureth sulfate 6

Disodium laureth sulfosuccinate 4

Laureth-3 3

Cocamidopropyl betaine 2.5

Sodium chloride 2

Dipropylene glycol 1

Parfum 0.5

Piroctone olamine 0.5

Panthenol 0.4

Propylene glycol 0.3

Disodium phosphate 0.25

Benzophenone-4 0.2

Wheat amino acids 0.15

Vitamin K Complex 1

Method

Stage 1

EDTA, Citric acid and Benzophenone-4 were added and mixed into the water. Sodium laureth sulfate, Disodium laureth sulfosuccinate and Dipropylene glycol were then added. Stage 2

Disodium phosphate, wheat amino acids and the Vitamin K Complex were added and the product was stirred until uniform.

Stage 3

The Piroctone olamine was dispersed in the parfum and added to the Laureth-3.

This mixture was added to the bulk and stirred.

Stage 4

The remaining materials were then added and the product was made to weight with purified water.

Example 37 - Anti-chlorine Shampoo %w/w

Aqua to 100

Sodium laureth sulfate 8

Cocamidopropyl betaine 3

Sodium chloride 1.6 Laureth-3 1

Phenoxyethanol 0.8

Parfum 0.5

Disodium phosphate 0.4

Panthenol 0.4 Propylene glycol 0.3

Methylparaben 0.2

Benzophenone-4 0.2

Wheat amino acids 0.14

Propylparaben 0.1 Sodium thiosulfate 0.1

Vitamin K Complex 1

Stage 1 To the water, the following materials were added and mixed; Benzophenone, Sodium chloride, Sodium phosphate, Disodium phosphate, EDTA.

Stage 2 Sodium laureth sulfate, phenoxyethanol, Panthenol, Wheat amino acids and the Vitamin K Complex were then added and stirred.

Stage 3

The preservatives were pre-mixed in the Laureth-3 and heated slightly to melt the powders. This was added to the product.

Stage 4

The remaining materials were added and the product was made to weight using purified water.

Example 38 - Hair Gel

%w/w

Aqua to 100

Cyclomethicone 7 Dimethiconol 1

Phenoxyethanol 0.8

Propylene glycol 0.8

Panthenol 0.7

Carbomer 0.7 Aminomethyl propanol 0.4

Benzophenone-4 0.2

Parfum 0.2

Vitamin K Complex 1

Method

Stage 1

To the water; EDTA and Benzophenone-4 were added using an homogeniser. Stage 2

The carbomer was added and hydrated with continued homogenising.

Stage 3

The Phenoxyethanol, Cyclomethicone, Dimethiconol, Propylene glycol and Panthenol were then added and mixed until homogenous.

Stage 4 The remaining materials including the Vitamin K Complex were added and the bulk was homogenised until uniform.

Stage 5

The product was made to weight using purified water.

Example 39 - Hair Putty

%w/w

Aqua to 100

Cetearyl alcohol 11 Lanolin 7

PVP 6

Paraffin 6

PVP/VA copolymer 6

Carnauba 3 Petrolatum 2

Polyquatemium-11 2

PEG-20 stearate 2

Paraffinum liquidum 1

Propylene glycol 0.8 Phenoxyethanol 0.6

Dimethicone 0.5

Panthenol 0.4

Cetrimonium chloride 0.35 Dimethicone propyl PG-betaine 0.25

Benzophenone-4 0.2

Methylparaben 0.12

Vitamin K Complex 1

Method

Stage 1

To the water, the PVP/VA copolymer, PVP and Benzophenone-4 were added and stirred until homogenous. This was then heated to 70°C.

Stage 2

In a separate vessel, the waxes were mixed and heated to 70°C until all materials had melted.

Stage 3

The hot waxes were then added to stage 1 and mixed using a propellor stirrer until homogenous. The mixture was then cooled to below 60°C.

Stage 4

The remaining materials, including the Vitamin K Complex were then added and the product was stirred until uniform.

Stage 5 The product was made to weight using purified water.

Example 40 - Hvdratino Conditioner

%w/w

Aqua to 100 Cetyl alcohol 4

Dimethicone 2

Hydroxyethylcellulose 0.8

Cetrimonium chloride 0.8 Panthenol 0.75

Propylene glycol 0.6

Parfum 0.3

Benzophenone-4 0.2

Amodimethicone 0.15 Dimethicone propyl PG-betaine 0.15 Sodium chloride 0.15 Vitamin K Complex 1

Method

Stage 1

To the water, EDTA and Hydroxyethylcellulose were added using homogenising to hydrate the polymer.

Stage 2

The benzophenone-4 and Laureth-3 were then added and the bulk was heated to

70°C.

Stage 3

In a separate vessel, the Cetyl alcohol was heated to 70°C until melted.

Stage 4

Using an homogeniser, the Cetyl alcohol was added to the bulk and mixed until uniform.

Stage 5

The product was cooled and the remaining materials, including the Vitamin K Complex were then added and mixed.

Stage 6

The product was made to weight using purified water. Example 41 - Spray-on Gel

%w/w

Phase 1

Aqua to 100 PVP/VA copolymer 5

Isopropyl alcohol 2.5

Propylene glycol 2.3

Glycerin 2

Panthenol 0.4 Benzophenone-4 0.2

Vitamin K Complex 1

Phase 2

PEG-40 hydrogenated castor oil 1 Parfum 0.5

Phase 3

Alcohol denat. 45

Dimethicone copolyol 1

Method

Stage 1

The materials in phase 1 were mixed until uniform using a propellor stirrer.

Stage 2

The materials in phase 2 were pre-mixed and added to phase 1.

Stage 3 The materials in phase 3 were mixed and added to the bulk.

Stage 4

The product was made to weight using purified water. Example 42 - Shampoo For Dry Scalps

%w/w

Aqua to 100

Sodium laureth sulfate 7

Sodium chloride 2.5

Cocamidopropyl betaine 2

Laureth-3 1

Panthenol 0.5

Propylene glycol 0.5

Piroctone olamine 0.25

Benzophenone-4 0.2

Vitamin K Complex 1

Method

Stage 1

To the water, EDTA, Citric acid, Benzophenone-4 and Sodium chloride were added and mixed using a propellor stirrer until all materials were dissolved and uniform.

Stage 2

The Sodium laureth sulfate and Piroctone Olamine were then added and stirred until homogenous.

Stage 3

The remaining materials, including the Vitamin K Complex were then added and the product was stirred until uniform and homogenous.

Stage 4

The product was made to weight with purified water.

Example 43 - Deep Cleansing Shampoo %w/w

Aqua to 100

Sodium laureth sulfate 15

Sodium chloride 2.8 Cocamidopropyl betaine 1.5

PEG-6 cocamide 1

Parfum 0.15

Panthenol 0.4

Propylene glycol 0.3 Benzophenone-4 0.2

Phenoxyethanol 0.1

Vitamin K Complex 1

Method

Stage 1

To the water, Citric acid, EDTA and Sodium chloride were added and dissolved.

Stage 2 The Benzophenone-4, Sodium laureth sulfate, Cocamidopropyl betaine,

Panthenol, Methydibromo glutaronitrile, Wheat amino acids and the Vitamin K Complex were then added and mixed until the product was uniform, using a propellor stirrer.

Stage 3

The parfum was pre-dispersed in the PEG-6 cocamide and then added to the bulk.

Stage 4 The product was made to weight using purified water.

Example 44 - Hvdratino Shampoo

%w/w Aqua to 100

Sodium laureth sulfate 8

Cocamidopropyl betaine 3

Cocamide DEA 1.7 Panthenol 1.2

Sodium chloride 1.5

Laureth-3 1.2

Parfum 0.5

Propylene glycol 0.5 Polyquaternium-10 0.4

Glycerin 0.2

Vitamin K Complex 1

Method

Stage 1

To the water, the EDTA and Polyquaternium-10 were added and the polymer was hydrated using an homogeniser.

Stage 2

The Citric acid, Sodium chloride and Benzophenone-4 were added and stirred until uniform.

Stage 3 The remaining materials, including the Vitamin K Complex were added individually and the product was mixed using a propellor stirrer until homogenous.

Stage 4

The product was made to weight using purified water.

Example 45 - Extra Hold Hair Gel

%w/w Aqua to 100 PVP/VA copolymer 2

Propylene glycol 1.3

Carbomer 1

PEG-40 hydrogenated castor oil 1

Panthenol 0.6

Sodium hydroxide 0.3

Parfum 0.3

Phenoxyethanol 0.2

Tetrasodium EDTA 0.1

Mica 0.1

Cystine hydroxypropyl polysiloxane 0.1

Vitamin K Complex 10

Method

Stage 1

Stage 2

Stage 3

The remaining materials, including the Vitamin K Complex were added individually and mixed using a propellor stirrer until the product was homogeneous.

Example 46 - Vitamin K Syrup mg per 10ml dose Sorbic acid 10

Sodium Citrate 50 Sodium chloride 10

Xanthan gum 40

Glycerin 3,400

Vit K complex 100

Sweet Orange Oil 13

Water to 10ml

Example 47 - Multivitamin Svrup mg per 10ml dose

Sorbic acid 10

Sodium Citrate 50

Sodium chloride 10

Xanthan gum 40

Glycerin 3,400

Vit K complex 100

Riboflavin-5-phoshate Sodium 1.64

Pyridoxine HCI 1.02

Nicotinamide 14

D-Panthenol 3.14

Ascorbic Acid 153.06

Thiamine HCI 1.207

Vit A Palmitate 1.7MIU/G 1.37 D3 1 MIU/G 0.56

DL-A-Tocopheryl Acetate 6.56

Sweet Orange Oil 13

Water to 10ml

Example 48 - Vitamin K tablet

Wt for 220mg tablet

Vit K complex 100

Sorbitol 108.5

Magnesium Stearate 1.5 Example 49 - Bruise reduction lotion

%w/w

Aqua to 100

Hydrated silica 5 Isopropyl palmitate 4

Arachidyl propionate 2

Dimethicone 2

Glycerin 2

Steareth-21 1.96 Steareth-2 1.683

Cetyl alcohol 1

Tribehenin 1

Glyceryl stearate 1

Paraffinum liquidum 0.994 Panthenol 0.75

Parfum 0.3

Xanthan gum 0.3

Sodium citrate 0.25

Tocopheryl acetate 0.2 Hydroxyethylcellulose 0.1

Bisabolol 0.095

Citric acid 0.05

Preservative q.s

Vitamin K Complex

Method

Stage 2

The isopropyl palmitate, arachidyl propionate, dimethicone, steareth-21 , steareth-2, cetyl alcohol, tribehenin, glyceryl stearate, paraffinum liquidum are mixed and heated to 70°C to melt the waxes.

Example 50 - Chilblain cream

%w/w

Aqua to 100

Glycerin 5

Paraffinum liquidum 4.5 Dicaprylyl maleate 3

Dimethicone 3

Petrolatum 3

Paraffin 2.9

Cetyl alcohol 2 Steareth-2 2

Glyceryl stearate 1.5

Butyrospermum parkii 1.5

Steareth-21 1

Mannitol 1 Cera microcristallina 0.262

Buxus chinensis 0.5

Propylene glycol 0.48

Parfum 0.4

Borago officinalis 0.3 Hydroxyethylcellulose 0.3

Lactis proteinum 0.3

Xanthan gum 0.25

Alcohol denat. 0.08 Sodium citrate 0.08

Lecithin 0.075

BHT 0.05

Faex 0.04 Phospholipids 0.03

Citric acid 0.025

Vitamin K Complex 5

Preservative q.s

Method

Stage 1

Stage 2

The paraffinum liquidum, dicaprylyl maleate, dimethicone, petrolatum, paraffin, cetyl alcohol, steareth-2, glyceryl stearate, steareth-21 , cera microcristallina and BHT are mixed and heated to 70°C to melt the waxes.

Stage 3

Stability of Vitamin K Complex

The physical stability of 1 % Vitamin K Complex was assessed using the formulation of Example 3. The aim was to determine both the stability of the Vitamin K Complex, and its effects on the stability of the emulsion. Formulation Example 3 was chosen as its stability is well known from previous studies.

The emulsion was prepared using the method described in Example 3, in standard laboratory conditions with no special lighting or vacuum systems.

The finished product was stored in glass jars at the following locations:

Ambient 30°C 40°C 3°C.

The samples were removed weekly, left to equilibrate for 3 hours and then assessed for any physical changes. The sample stored at 3°C was used as the standard to compare discoloration. Microscopy was also conducted using an Olympus BH-2 Electron Microscope at 40x magnification to assess any changes to the emulsion structure and identify any crystallisation of sensitive raw materials.

Over a period of three months, there was no deterioration in the physical stability of the emulsion samples, with no discoloration, odour development or structural changes. The pH and viscosity of each sample also remained stable over the 3-month period.

The sample stored at ambient conditions was submitted for analysis (by the assay method described below) to determine the level of Vitamin K1 present following the 3-month study. It was determined that following the study, there was 0.1% Vitamin K1 present in the emulsion. This was 100% of the original loading, as the Vitamin K Complex contains 10% Vitamin K1.

The 40°C sample was stored for a further 3 months as a very rigorous stability challenge. Following this period, there was a slight discoloration to the emulsion when compared to the 3°C sample. The discoloration observed was expected from the emulsion and its inherent stability, and was not believed to be due to the Vitamin K Complex material.

Following this additional stability study, the sample was submitted for analysis to determine the level of Vitamin K1 present. It was found that following the study, there was 0.054% Vitamin K1 present in the emulsion. This was approximately 50% of the original loading, which represents a surprisingly high level of vitamin K retention in view of the severity of the conditions under which the sample was stored.

Vitamin K1 Assay HPLC METHOD

Reagents

Vitamin K1 standard. HPLC grade methanol. Routine laboratory instruments and glassware (volumetric flasks, graduated pipettes, syringe for HPLC, analytical balance).

HPLC Instruments and conditions

HPLC: apparatus with UV-VIS detector λ: 254 nm

Sensitivity: 0.125 AUFS Column: C18 reversed phase Chromopack, high resolution, with pre-column. Length 10 cm, internal diameter 8 mm.

Flow rate: 1 ml/min

Eluent: 100% HPLC grade methanol

Procedure

Standard preparation Prepare a Vitamin K1 standard solution in methanol (corresponding to the amount supposed to be present in 1g of sample) and filter it. The clear solution can be directly injected into the HPLC apparatus.

Sample preparation

Weigh exactly 1g sample in a 100 ml volumetric flask and bring to volume with methanol (or any other solvent appropriate to the matrix containing the vitamin); shake vigorously for 5 min, then filter. The clear solution can be directly injected into the HPLC apparatus.

Analysis

Measure the standard area, compare it with that of the sample and calculate the sample concentration.

Claims

1. A composition comprising, as active ingredient, vitamin K, wherein the vitamin K is present as a complex with a cyclodextrin.

2. A composition as claimed in Claim 1 , wherein the cyclodextrin with which the vitamin K is complexed is a naturally occurring cyclodextrin.

3. A composition as claimed in Claim 2, wherein the naturally occurring cyclodextrin consists of six, seven or eight (respectively α-, β- and γ-cyclodextrin) D-glucopyranosyl units connected by α-(1 ,4)-glycosidic linkages.

4. A composition as claimed in Claim 3, wherein the cyclodextrin is β-cyclodextrin.

5. A composition as claimed in Claim 1 , wherein the cyclodextrin is a chemically modified cyclodextrin.

6. A composition as claimed in Claim 5, wherein the chemically modified cyclodextrin is selected from the group consisting of methyl cyclodextrins, hydroxyethyl cyclodextrins, hydroxypropyl cyclodextrins, glucosyl cyclodextrins, maltosyl cyclodextrins, carboxymethyl cyclodextrins and carboxyethyl cyclodextrins.

7. A composition as claimed in any preceding claim, wherein the cyclodextrin comprises seven glucopyranosyl monomer units, or chemically modified glucopyranosyl monomer units.

8. A composition as claimed in any preceding claim, wherein the vitamin K compound is vitamin K1.

9. A composition as claimed in any preceding claim, comprising a mixture of vitamin K compounds.

10. A composition as claimed in Claim 9, wherein the mixture includes vitamin K1 as the predominant component.

11. A composition as claimed in any preceding claim, wherein the composition is formulated as an emulsion.

12. A composition as claimed in Claim 11 , wherein the composition is formulated as a gel.

13. A method for the alleviation or treatment of bruising, which method comprises application to an area of human or animal skin affected by bruising of a composition as claimed in any preceding claim.

14. A cosmetic method for improving the appearance of the skin, which method comprises applying to the skin a personal care composition comprising, as active ingredient, vitamin K, wherein the vitamin K is present as a complex with a cyclodextrin.

15. A cosmetic method as claimed in Claim 18, which is a method for improving the appearance of the skin around the eyes, in particular a method for the cosmetic treatment of dark areas ("shadows") in the vicinity of the eyes.

16. A method for the treatment of a condition selected from the group consisting of bruising, thread veins, chilblains, dry skin, cracked skin, scaly skin, psoriasis, eczema and ichthyosis, which method comprises administration of vitamin K to a patient suffering from, or susceptible to, such a condition, wherein the vitamin K is in the form of a complex with a cyclodextrin.

17. The use of vitamin K in the form of a complex with a cyclodextrin in the manufacture of a medicament for the treatment of a condition selected from the group consisting of bruising, thread veins, chilblains, dry skin, cracked skin, scaly skin, psoriasis, eczema and ichthyosis.