GB2391808A

GB2391808A - Lanolin hydrocarbon containing compositions from the reduction of lanolin or lanolin-derived feedstock

Info

Publication number: GB2391808A
Application number: GB0317524A
Authority: GB
Inventors: Ian Steel
Original assignee: Croda International PLC
Current assignee: Croda International PLC
Priority date: 2002-07-26
Filing date: 2003-07-28
Publication date: 2004-02-18
Anticipated expiration: 2023-07-28
Also published as: AU2003251362A1; GB0217366D0; GB2391808B; WO2004011581A1; GB0317524D0

Abstract

A composition is provided which is formed by the reduction (eg catalytic hydrogenation) of lanolin or a lanolin-derived feedstock and which comprises at least 25 % w/w of lanolin hydrocarbons and no more than 75 % w/w of lanolin alcohols based on the total weight of the composition. There is also provided a formulation comprising such a composition and a carrier The lanolin hydrocarbon content of the composition preferably comprises from 15 to 45% each of n-alkanes, 2-methylalkanes and 3-methylalkanes having from 8 to 40 carbon atoms. The composition may be prepared by extended hydrogenation of lanolin fatty acid esters (obtainable by esterification of lanolin fatty acid with iso-propyl alcohol) or hydrogenation of woolwax alcohols (obtainable by hydrogenation of lanolin fatty acid esters). The formulation may be in a form suitable for dermatological or topical administration and use to treat of prevent conditions such as skin barrier damage, wounds, burns, granulated skin tissue, rough skin, trans-epidermal water loss, epithelial damage, dry skin, itching eczema, dermatitis, inflammation or inflammatory conditions, or microbial infection such as S. aureus infection. The formulation may be used as a carrier for cosmetic or pharmaceutically active agents. The formulation may also be in a form suitable for industrial, household or agricultural applications.

Description

1 2391808

Compositions The present invention relates to novel reduced lanolin products, particularly those comprising a high lanolin hydrocarbon content, processes for preparing them, 5 especially catalytic hydrogenation, and their use, particularly in topical formulations.

Lanolin' is the best-known name for refined wool wax, which is a naturally-occurring substance first identified millennia ago in washed, shorn sheep's wool. It was recognised as an outstanding emollient for the skin when used in ointments. Wool 10 wax is a true wax in the chemical sense, there being no glycerides present, but rather it comprises a highly complex mixture of esters of fatty alcohols with fatty acids, both of which are of several different types and covering a wide range of molecular weight.

15 A typical composition of a pharmaceutical grade lanolin comprises, by weight: Water 0.05% Free fatty acids 0.3% Free fatty alcohols 8.0% Wax ester 91.5% Much of the lanolin now produced is used within the industry for derivatisation. To date, the most important derivatives include the lanolin alcohols (the unsaponifiable 20 fraction of lanolin) and lanolin oil (the liquid ester fraction of lanolin). Both of these are used extensively in cosmetics and toiletries; lanolin alcohols are also important in the pharmaceutical industry. Lanolin also contains a small amount of hydrocarbons, referred to as 'paraffins' by the European Pharmacopoeia (EP) and as 'petrolatum' by the US Pharmacopoeia. The maximum permitted amount of 25 lanolin hydrocarbons is 1% by weight determined (EP) by column chromatography on activated aluminium oxide.

Lanolin alcohols can be prepared by reduction, as described in British patent specification no. 2 058 777, which discloses two routes for converting wool wax

30 acids to their corresponding alcohols via hydrogenation. The first route involves in situ esterification of distilled wool wax acids with a low molecular weight alcohol followed by high-pressure hydrogenation. The second route simply uses a pre

prepared ester (eg methyl, ethyl, isopropyl, etc.) as the hydrogenation substrate.

Unwanted by-products, namely ar,-diols, which have pronounced anti emulsification properties, could be separated from the resultant fatty alcohols by either molecular distillation or crystallization.

The focus of such processes hitherto has been on obtaining lanolin alcohols, with a minor proportion of the product of such reduction processes comprising hydrocarbons. Such prior art products therefore generally contain no more than

10% lanolin hydrocarbons and a correspondingly high proportion of lanolin alcohols 10 (generally at least 90%).

We have now surprisingly found that reduced lanolin can be prepared, comprising a high proportion of lanolin hydrocarbons, which have excellent emollient properties, are aesthetically pleasing (which would, in use, improve compliance), and have 15 potential in anti-inflammatory, barrier repair and anti-itch properties, particularly for wound healing.

By "reduced lanolin" herein is meant the products of the process of the extended reduction of lanolin or lanolin-derived feedstock, whether produced by a process 20 such as described in more detail below or by an alternative method. For example, such reduced lanolin products may alternatively be obtained by one or more synthetic chemical methods and/or by extraction or concentration of naturally- t occurring hydrocarbons and other components of lanolin. Although the preferred feedstock for the reduction is isopropyl lanolate, particularly the solid fraction of: 25 isopropyl lanolate as mentioned below, the reduced lanolin products of the invention i may be prepared by reduction of lanolin or a lanolin derivative, such as other lanolin fatty acids esters, woolwax alcohols, lanolin fatty acids and lanolin alcohols. i The reduced lanolin products of the invention preferably comprise at least 15% 30 lanolin hydrocarbons, with the balance comprising partially- reduced lanolin derivatives, such as lanolin alcohols. Accordingly, the present invention provides a lanolin-derivable composition comprising at least 25% w/w of lanolin hydrocarbons and at most 75% w/w lanolin alcohols, based on the total weight of the composition.

Preferably, the composition comprises at least 50% w/w of lanolin hydrocarbons;! 35 more preferably, at least 75% w/w of lanolin hydrocarbons, and, especially, at least i 90% w/w of lanolin hydrocarbons.

In particular, the reduced lanolin products of the invention are preferably substantially lanolin ester-free, that is to say that less than 2% of the reduced lanolin product comprises lanolin ester reduction feedstock. Especially preferred is when 5 the reduced lanolin product comprises less than 1% lanolin ester reduction feedstock. Chemical synthesis of reduced lanolin products of the invention may be undertaken by extended hydrogenation using a method analogous to the above-mentioned 10 known processes for preparing lanolin alcohols. By 'extended. hydrogenation is herein meant hydrogenation undertaken under such conditions and for a sufficient period of time to enable production of the reduced lanolin having high hydrocarbon content, as defined herein. Such conditions and/or time period are in excess of those required to produce the lanolin alcohols. An attempt to use the first route 15 mentioned above, using distilled wool wax acids (lanolic acid) and ethanol, revealed significant problems. Although the alcohols obtained were almost identical (with regard to wet chemical analysis), the hydrogenation (and indeed the esterification) had not gone to completion in the time specified in the patent (4 hours). In total, a further 46 hours of reaction were needed to produce a fully hydrogenated product.

A new process was proposed, which involves the reduction of distilled short chain alkyl esters of lanolin fatty acids using the second route. As well as an improved yield, this feedstock provides a product that contains an increased proportion of higher molecular weight reduced lanolin species.

The reduction feedstock may be prepared by reaction of lanolin fatty acids and a short chain aliphatic alcohol, such as ROH wherein R is C,.4 alkyl, preferably i isopropyl (IPA), and a suitable catalyst. A preferred catalyst is para-toluene sulphonic acid (ULTRA), although other conventional esterification catalysts (such as 30 those mentioned in patent specification no. WO 98/30532) may be used. Using IPA

as the alcohol: after removal of excess IPA, the crude ester can be basewashed to yield crude low acid value isopropyl lanolate. The crude isopropyl lanolate can then be split by molecular distillation to yield solid and liquid fractions, which contain isopropyl esters of C16- C40 lanolin fatty acids & C8 - C22 lanolin fatty acids,! 35 respectively. i

Preferably, the solid fraction of low acid value isopropyl lanolate is used as the reduction feedstock. More preferably, the feedstock is free of typical catalyst poisons (sulphur, chlorine & heavy metals) and has an acid value of less than 1 mgKOHg'.

Still more preferred is when lower molecular weight lanolin fatty acid esters tC14 5 and lower) are excluded from the reduction feedstock. Reduction of the isopropyl lanolate feedstock yields the reduced lanolin system. Reduction is preferably carried out by catalytic hydrogenation.

Hydrogenation may be carried out in the presence of a suitable hydrogenation 10 catalyst at a high pressure in the range of from 100 to 30850 kPa, more preferably in the range 17450 to 30850 kPa, and a temperature in the range of from 100 to 300 C, more preferably in the range 200 to 300 C. The resultant reduced lanolin products can be purified, preferably by molecular distillation. A preferred hydrogenation catalyst for this process is copper chromite.

Hydrogenation may be carried out also in the presence of a suitable hydrogenation catalyst at a high pressure in the range of from 100 to 30850 kPa, more preferably in the range 17450 to 30850 kPa, but at a temperature greater than 350 C. The resultant reduced lanolin products can again be purified, preferably by molecular 20 distillation. Preferred hydrogenation catalysts for this process are metals such as Ni, Co, Rh or Ru, supported on alumina, silica or TiO2.The extended reduction, especially hydrogenation, process of the invention accordingly provides novel reduced lanolin products.

25 A typical composition according to the invention is one wherein the lanolin hydrocarbon content comprises in the range of from 15 to 45%, such as 20 to 40%, each of n-alkanes, 2-methylalkanes and 3-methylalkanes, based on the total weight of the lanolin hydrocarbons in the composition. Preferably the lanolin hydrocarbons each comprise in the range of from 8 to 40, such as 12 to 32 carbon atoms.

In another aspect, the present invention provides a composition according to any preceding claim, preparable by extended hydrogenation of lanolin fatty acid esters, especially wherein the lanolin fatty acid esters are obtainable by reaction of lanolin fatty acids with iso-propyl alcohol.

Because of the lanolin derivative content of the compositions according to preferred embodiments of the invention, they find particular use in the treatment of parts of the mammalian body, especially the skin, for various purposes. Thus, suitable topical delivery forms may include sprays, aerosols, liniments, lotions, bath dispersions, 5 shampoos, drenches, ointments, pastes, creams, gels, salves and patches and may also comprise non-topical forms such as pessaries, suppositories or any other suitable dosage form such as is typically used for the delivery of cosmetically or pharmacologically active agents. The formulations may accordingly comprise oil-in-

water or water-in-oil or complex emulsions, or solutions or suspensions.

Drops according to the present invention may comprise sterile aqueous or oily solutions and may be prepared by dissolving the active ingredient in a suitable aqueous solution containing a bactericide and/or fungicidal agent and/or any other suitable preservative. The resulting solution may then be clarified by filtration, 15 transferred to a suitable container, and then sealed and sterilized by autoclaving or maintaining at 90-100 C for half an hour. The solution may be sterilized by filtration and transferred to the container by an aseptic technique. Preservatives, bactericidal and fungicide agents suitable for inclusion in the drops are phenylmercuric salts (0.002%), benzalkonium chloride (0.01 %) and chlorhexidine acetate (0.01%).

20 Suitable solvents for the preparation of an oily solution include glycerol, diluted alcohol and propylene glycol.

Lotions according to the present invention include those suitable for application to the eye. An eye lotion may comprise a sterile aqueous solution optionally containing 25 a bactericide or preservative prepared by methods similar to those for the preparation of drops. Lotions or liniments for application to the skin may also include an agent to hasten drying and to cool the skin, such as an alcohol, or a softener or moisuriser such as glycerol or an oil such as castor oil or arachis oil.

30 Creams, ointments or pastes according to the present invention are semi-solid formulations of the active ingredient for external application. They may be made by mixing the active ingredient in granule or powdered form, alone or in solution or suspension in an aqueous or non-aqueous solution in suitable machinery, with a greasy or non-greasy basis. The basis may comprise one or more of a hard, soft or 35 liquid paraffin, glycerol, beeswax, a metallic soap; a mucilage; an oil such as vegetable oil, eg almond, corn, arachis, castor or olive oil; wool fat or its derivatives;

or a fatty acid ester of a fatty acid together with an alcohol such as propylene glycol or macrogols. The formulation may also comprise a suitable surface-active agent, such as an anionic, cationic or non-ionic surfactant such as glycol or polyoxyethylene derivatives thereof. Suspending agents such as natural gums may 5 be incorporated, optionally with other inorganic materials such as silicaceous silicas, and other ingredients such as lanolin or other lanolin derivatives.

The compositions of the invention may further be used as skin moisturizers or for the provision of a film or barrier to allow both the delivery of medicaments to 10 underlying traumatised skin (eg to wounds, burns, ulcers) or to eczematous or psoriatic skin or to areas of generalized dry or damaged skin or hair, eg following excessive exposure to the sun or wind or after radiation or chemotherapy treatments, and also to prevent the actions of airborne infections to such aforesaid traumas. The compositions, particularly for use as a sunscreen, include one or more of a moisturizer, an emollient, an emulsifier, a preservative, a dispersant, a viscosity modifier, a herbal extract, a solvent, a chelating agent, an antioxidant, a water-

proofing agent, a pH adjuster, a perfume, and a protein.

The composition may include one or more of: titanium dioxide, zinc oxide, benzophenone-3; benzophenone -; octyl methoxycinnamate (Parsol 1789); 3,3, 5-

trimethylcyclohexyl salicylate; carbomer; hydroxyethyl cellulose; lanolin alcohols; cetyl phosphate; fatty alcohols; C72 to C75 alkyl benzoate; cyclomethicone; 25 caprylic/capric triglycerides; mineral oil; glycerin; vitamin E; and isopropyl myristate.

According to another aspect of the invention, we provide a pharmaceutical formulation for treating skin inflammation caused by burns, by exposure to sunlight or by exposure to UV radiation, comprising a composition of the invention and a 30 physiologically acceptable carrier.

The carrier may therefore include excipients normally present in formulations for treating burns, such as antiseptic compounds, emollients, inorganics, humectants, moisturisers, anti-inflammatory agents, vitamins, preservatives, pH adjusters, 35 proteins, herbal extracts, carriers/solvents, soothing/cooling agents, antioxidants, perfumes, emulsifiers and viscosity modifiers. Specific examples of useful materials

include glycerine, triethanolamine stearate, vitamin E, lanolin, zinc oxide, allantoin, calamine, sodium lactate, water, lactic acid, provitamin B5 and menthol.

The compositions of the invention also find use as carriers for one or more cosmetic 5 or pharmaceutical active agents which are incorporated into the compositions so that they may be efficiently delivered to the skin, mucosae or other parts of the body by application of the composition thereto.

In accordance with this aspect of the invention, a wide range of cosmetically, 10 dermatologically and/or pharmaceutically active agents may be incorporated into the compositions of the invention, examples of which are well known in the art. A wide variety of suitable such bigaffecting active agents are disclosed, for example, in US patent specification no. 4560553. The amount of active which is incorporated may

be selected according to the amount required to be delivered, which again will 15 generally be in accordance with well established principles and formulation techniques. The compositions of the invention may also be used as vehicles for transdermally delivered drugs in pharmaceutical or veterinary applications.

The compositions of the invention may also find use in industrial, domestic or 20 agricultural applications. Such applications may include treatment of leather, treatment of textiles, inks, metal-working, rust preventatives, cutting fluids, lubrication, penetrating oils, tissuesoftening, fabric care, furniture, shoe & leather polishes, crop protection and as an agrochemical active or for delivery of agrochemical actives.

The invention will now be further described with reference to the following examples.

ExamnIe 1: Preparation of Reduced Lanolin Product A. Production of hydrogenation feedstock 5 Crude low acid value (2 mgKOHg'') isopropyl lanolate (prepared by acid-catalysed esterification of lanolin fatty acids and isopropyl alcohol) was distilled in two passes to yield the solid fraction of isopropyl lanolate with an acid value of between 1 and 2 mgKOHg'. Free fatty acid was saponified by addition of sodium carbonate and the solid isopropyl lanolate fraction was redistilled to give low acid value (1 mgKOHg-) 10 isopropyl lanolate (solid fraction) hydrogenation\ feedstock.

Typical analysis for the hydrogenation substrate is shown in the table below.

Parameter | Result | Acid value/ mgKOHg' 0.94 Saponification value/ mgKOHg'' 127.1 Hydroxyl value/ mgKOHg 1 51.3 iodine value/ gl2(100g)'' 11. 5: Sulphur contend ppm 17 B. Hydrogenation of Low Acid Value Solid Isopropyl Lanolate By a method analogous to the following protocol of GB 2 058 777, but replacing the woolwax acids with the low AV Isopropyl lanolate and omitting the ethanol, was prepared the hydrogenated product: 20 500g of low acid value solid isopropyl lanolate & 259 of copper chromite were charged into a 2 litre autoclave. After flushing the apparatus with nitrogen, hydrogen was introduced into the apparatus under a pressure of 18000 to 190000 kPa and the reaction vessel heated to 290 to 300 C. The pressure was increased to 28000 to 30000 kPa in order that, during the course of 8 hours, the pressure settled at a 25 constant value of 26000 to 27000 kPa. After cooling the reaction mixture was removed from the autoclave and the catalyst filtered off to yield the crude lanolin hydrocarbon product.

B1. Hydrogenation using methodology exemplified in FR 2 607 803 50Og of low acid value solid isopropyl lanolate & 11.29 of catalyst, Ni/SiO2 (containing 8% w/w of Ni), were charged into a 2 litre autoclave. The vessel was 5 purged, then pressurised to 15000 kPa with hydrogen & heated to 360 C. Further hydrogen was introduced to give a total pressure of 22000 kPa and a partial pressure of hydrogen of approximately 18000 kPa. This pressure was maintained at a constant level by further additions of hydrogen, as necessitated by consumption from the reaction. The reaction mixture was stirred mechanically at this pressure 10 and at a temperature of 360 C for 2 h. After cooling and depressurisation, the colourless liquid phase was separated form the catalyst by filtration to yield the crude lanolin hydrocarbon product.

C1. Post-hydrogenation processing of hydrocarbons - Molecular Distillation Analysis of crude hydrocarbons Test Result Acid Value / mgKOHg'' 0.00 Hydroxyl Value / mgKOHg'' 4.0 Saponification Value / mgKOHg- 4 1.2 Drop Point / C 31.5 Coiour 0.4Gardner / 60Hazen The crude hydrocarbons were purified by distillation on a laboratory scale molecular 20 still.

The conditions employed were as follows: Condenser Evaporator Vacuum/ Feed rate/ Total Tl C T/ C mbar gh'' charge/ 9 60 145 6 x 10- Z 154 295.8 25 The following mass balance was obtained:

Mass/g % Distillate 253.0 85.5 Residue 35.4 12.0 Losses i.4 2.5 Analysis of refined hydrocarbons ax-molecular distillation Test Result Acid Value/ mgKOHg-' 0.05 Hydroxyl Value / mgKOHg-' 0.4 t Saponification Value / mgKOHg' 0.7 Peroxide Value / meqO2kg- 0.00 Colour 0.0Gardner/ 3Hazen 5 Composition of distilled hydrocarbons by GO A portion of the hydrocarbon product was dissolved in heptane and analysed using a 100% dimethylpolysiloxane capillary column (RH-1 or equivalent), 30 m x 0.25 Am i.d., film thickness 0.2 mm. The injector and detector temperatures were 285 and 10 300 C, respectively.

The oven program was as follows: Initial T = 120 C Initial time = 2.5 min Ramp rate = 6 C/min Final T = 275 C Final time = 27 min Peaks were assigned using a combination of standards for the n-alkanes and standards & theoretical elusion orders for the 2- & 3-methylalkanes.

n-Alkanes 2-Methylalkanes 3-Methylalkanes Tota I Area Tota I Area Tota I Area carbon % carbon % carbon % number number number C13 0.2 C14 0. 1 C14 0.3

C14 1.9 C15 0.9 C15 0 1

C15 6.2 C16 1.6 C16 1.2

C16 2.5 C17 5.0 C17 0.3

C17 3.4 C18 2.1 C18 4.2

C18 0.6 C19 5.5 C19 0.8

C19 1.1 C20 1.5 C20 5.6

C20 0.3 C21 3.2 C21 1.2

C21 1.2 C22 1.5 C22 3.3

C22 0.4 C23 4.2 C23 1.0

C23 _ C24 _ C24 _

C24 0.7 C25 4.9 C25 0.6

C25 3.3 C26 0.5 C26 4.8

C26 0.6 C27 1.7 C27 0.4

C27 1.3 C28 0.4 C28 1.7

C28 0.4 = =

C29 0.4 - C29 0.6 C30 0.7

C30 0.2 C30 C31

= C31 0 1 C32 0 1

Group total 28.8 Group total 35.0 Group total 32.5 Unknowns = 5.8% S These data indicate that the hydrocarbon product contains a range of hydrocarbons from C13 up to C32, although trace amounts of lower hydrocarbons may also be present. The group totals for n-alkanes, 2methylalkanes & 3-methylalkanes are 28.8, 35 and 32.5%, respectively.

ExamnIe 2: Analvsis of Solid & Liouid Fractions of Lanolin Hvdrocarbons Distilled hydrocarbon product (29.98 9), produced according to Example 1 (C1), was allowed to equilibrate at 22 C. After a sufficient length of time (24 to 96 h), the 5 clear liquid fraction was separated from the solid fraction by decantation.

n-Alkanes 2Methylalkanes 3-Methylalkanes Total Area % Total Area % Total Area % carbon carbon carbon number number number Solid Liquid Solid Liquid Solid Liquid C13 0.2 C13 0.1 C14 0.3

C14 O.Z 1.8 C14 = 0.1 C15 0.1

C15 1.1 7.2 C15 0.1 1.0 C16 0.2 2.0

C16 0.7 3.1 C16 0.2 2.0 C17 0.1 0.4

C17 1.4 4.1 C17 0.7 6.5 C18 0.6 5.4

C18 0.4 0.7 C18 0.3 2.6 C19 0.1 1.0

C19 1.1 1.1 C19 1.2 6.9 C20 1.1 7.0

C20 04 0.3 C20 0.5 1.8 C21 0.3 1.5

C21 2.1 0.9 C21 1.6 3.6 C22 1.4 3.9

C22 0.9 0.3 C22 1.2 1.6 C23 0.7 1.1

C23 10.0 2.1 C23 4.8 3.8 C24 6.2 5.9

C2-4 18 0.3 C24 1.7 0.9 C25 0 9 0.6

C25 9.5 1.2 C25 9.4 3.2 C26 8.7 3.5

C26 1.B 0.2 C26 1.1 0.3 C27 0.6 0.3

_ _ C27 4.3 0.4 C27 4.7 0.9 C28 4.5 1.1

C28 2.4 0.4 C28 0.5 0.4 C29 0.3 0.1

C29 1.5 0.1 C29 2.3 0.3 C30 2.2 0.4

C30 0.6 0.1 C30 0.2 0.1 C31 0.1

C31 0.6 C32 0.5

Group total 40.2 24.5 Group 31.1 36.1 Group 28.5 34.6 total total Yield of liquid = 22.05 g(73.5%) Yield of solid = 7.93 g(26.5%)

Example 3: In viva assessment of the effect of Lanolin derived hydrocarbons on skin roughness and moisturisation bv Profilometrv and Corneometry A. Profilometry Skin surface contour analysis (microprofilometry) was performed by taking silicone replicas of the skin. These were then analysed by a mechanical profilometric technique, using the Hommel tester T-1000 (Hommelwerke GmbH).

10 The liquid fraction of lanolin hydrocarbons was assessed against a blank, a positive control (Mineral oil, 25cs) & a negative control (silicone, 345). The results are tabulated below: Number of % Change after Parameter Product volunteers 2 h 4.5 h Blank 12 -0.56 Lanolin hydrocarbons 12 -6.04 Ra Lanolin hydrocarbons 16 -8.60 Silicone 16 +3.25 Mineral Oil 16 -5.83 Blank 12 -1.25 -3.40 Lanolin hydrocarbons 12 -5.1 -0. 98 Rz (ISO) Lanolin hydrocarbons 16 -8.40 -2.21 Silicone oil 16 +4.91 +8. 69 Mineral Oil 16 -5.19 -0.82 15 Student T-tests were performed on the results of the profilometry.

T-Test: 2 & 4.5 h p calculated Degrees of Comparison Parameter 2 h 4.5 h Freedom Lanolin hydrocarbons Ra P - Q.39 11 vs Blank Rzl p=0.40 095 11 Lanolin hydrocarbons Ra p = 0.32 15 vs Mineral Oil p = 0.29 p = 0.45 15 Lanolin hydrocarbons Ra p = 0.04 15 vs Silicone Oil p = 0.05 p = 0.04 15 The results after 2 hours show that the decrease in skin roughness was significantly greater for those sites treated with lanolin hydrocarbons compared to those treated 5 with silicone oil.

No significant difference was noted between the effects of the lanolin hydrocarbons and mineral oil.

10 The lanolin hydrocarbons demonstrated a significant decrease in Rzl compared to silicone at both 2 and 4.5 hours.

In the short-term, the skin roughness profile decreased significantly after application of the lanolin hydrocarbons compared to the silicone oil. The results were not 15 significantly different when compared to those for mineral oil.

The positive control, mineral oil, a known emollient, was found to cause a significant increase in skin smoothness whereas the blank site showed little change.

20 Corneometry Moisturisation of the stratum corneum causes it to swell, making the skin's surface smoother. The "moisturizing potential" of a compound is therefore a valuable parameter used to assess the efficiency of an emollient.

The Corneometer CM825 (C+K, Germany) is an instrument which enables the determination of the water content of the stratum corneum by capacitance. This measurement is based on the completely different dielectric constant of water (81)

and other substances (mostly c 7). The measuring capacitor shows changes of capacitance according to the moisture content of the samples. A glass lamina separates the metallic tracks (gold) in the probe head from the skin in order to prevent current conduction in the sample.

5 During the measurement, a scatterfield penetrates the very first layer of the skin and

determines the dielectricity. The penetration depth is very low at only 3040'um.

% change in skin Number of Product moisturisation after volunteers 2 hours 4.5 hours Blank 12 6.5 4.6 Lanolin hydrocarbons 12 16.7 12.3 Lanolin hydrocarbons 16 16.7 12.3 Silicone 16 4.2 6.9 Mineral Oil 16 13. 5 6.4 T Test results - 2 & 4.5 h p value after Degrees of Freedom Comparison 2 h 4.5 h After 2 h After 4.5 h. Lanolin hydrocarbons vs Blank p = 0.01 p 0.16 11 10 Lanolin hydrocarbons vs Mineral Oil p = 0.3 p = 0. 17 15 14 Lanolin hydrocarbons vs Silicone Oil pa 0.01 p = 0.10 15 14 * One volunteer taken out of evaluation for this time period.

In the short term, (i.e.), 2 hours after application of lanolin hydrocarbons, the 15 moisture content of the skin was increased significantly compared to the sllicone-

treated and blank sites. However, there was no significant difference between the results for lanolin hydrocarbons and those for mineral oil.

No significant difference was observed after 4.5 h between the lanolin hydrocarbons 20 and either the blank, silicone oil or mineral oil.

Example 4: Sensorv Analvsis Protocol 5 The liquid fraction of Lanolin hydrocarbons was compared to mineral oil and approximately four hours later to silicone oil. Each product (2mg/cm2) was applied to the forearm of the volunteer, who was then asked to rub in the product himself.

Application of the products was randomised. A total of 28 volunteers, 13 male and 15 female, took part in the trial.

Volunteers were asked if they could notice any difference between the two & those who could were then asked which product they preferred. Once the application sites were dry, the volunteers were asked which product they preferred in terms of after-

feel. 1 5 Results Results were collated and calculated as percentage values - these are presented in the following tables for each comparison.

Lanolin hydrocarbons versus Mineral Oil Preference of Preference of Product application (%) after-feel (%) Lanolin hydrocarbon 51.7 58.6 Mineral oil 27.6 31.0 None 20.7 10.4 Lanolin hydrocarbons versus Silicone Oil Preference of Preference of Product application (%) after-feel (%) Lanolin hydrocarbon 41.4 55.2 Silicone 44.8 37.9 None 13.8 6.9 _._ 25 The results indicate an obvious preference toward the lanolin hydrocarbons compared to mineral oil for both application and after-feel.

When compared to the silicone oil, fewer volunteers (41%) preferred the lanolin hydrocarbons for application compared to 45 % who preferred silicone. However in terms of after-feel, 55% preferred the lanolin product.

5 Example 5: Results of patch test studies All patch test studies were conducted in accordance with ICDRG guidelines.

10 Patch test results - Succesive presentations Patients attending a Contact Dermatitis Clinic have been tested to a liquid & solid fraction of a Croda Lanolin derivative. Both these fractions were tested "as is". Patch tests were examined for erythema, surface change & size of reaction according to 15 the trial protocol. Reactions were assessed clinically as either allergic or irritant. Results: Total number tested = 70 (Males 27, females 43) Atopy: Patients

with a past or current diagnosis of atopic eczema or asthma = 26 Findings with Croda preparation: 25 No reaction = 68 (no allergic or irritant reactions) Only two patients reacted, both males One was an individual with atopic eczema, who reacted to both fractions and whose 30 back had the appearance of the so-called 'angry back' reaction. Clinically the patch tests looked like an allergic reaction but this would have needed further testing to confirm. One non-atopic individual reacted to the liquid fraction with mild erythema only at 35 day 4.

Findings with Standard Series: Negative patch tests - 40 Positive patch tests = 30 The most frequent allergens to give positive reactions were the metals, i.e., nickel, cobalt & chromate, the Fragrance mix, and the aminoglycoside antibiotics.

The results suggest that this preparation has been non-irritant in the majority of 10 patients tested. One patient experienced a minor irritant reaction. It is difficult to draw any conclusion with regard to the other positive reaction observed.

Patch test results - Patients with chronic lea ulcers Number of patients tested = 41, of which 37 showed no allergic or irritant reactions.

The 4 that reacted showed minimal erythema as detailed below: 2 patients reacted to the solid fraction at day 2 1 patient reacted to the liquid fraction at day 4 20 1 patient reacted to a mixture of solid/liquid at day 4.

Claims

1. A composition formed from the reduction of lanolin or a lanolinderived 5 feedstock, said composition comprising at least 25% w/w of lanolin hydrocarbons and at most 75% w/w lanolin alcohols, based on the total weight of the composition.

2. A composition according to claim 1, comprising at least 50% w/w of lanolin hydrocarbons.

3. A composition according to claim 1 or claim 2, comprising at least 75% w/w of lanolin hydrocarbons.

4. A composition according to any preceding claim, comprising at least 90% 15 w/w of lanolin hydrocarbons.

5. A composition according to any preceding claim, wherein the lanolin hydrocarbon content comprises in the range of from 15 to 45% each of nalkanes, 2-

methylalkanes and 3-methylalkanes, based on the total weight of the lanolin 20 hydrocarbons in the composition.

6. A composition according to any preceding claim, wherein the lanolin hydrocarbons each comprise in the range of from 8 to 40, such as 12 to 32 carbon atoms.

7. A composition according to any preceding claim, preparable by extended hydrogenation of lanolin fatty acid esters.

8. A composition according to claim 8, wherein the lanolin fatty acid esters are 30 obtainable by reaction of lanolin fatty acids with isopropyl alcohol.

9. A method for the preparation of a composition according to any preceding claim, which method comprises hydrogenation of woolwax alcohols.

35

10. A method according to claim 9, wherein the woolwax alcohols are obtainable by hydrogenation of lanolin fatty acid esters.

11. A method according to claim 9 or claim 10, wherein the composition is prepared by extended hydrogenation of the lanolin ester product of an esterification reaction between lanolin fatty acids and iso-propyl alcohol.

12. A method according to claim 11, wherein the esterification reaction is undertaken in the presence of a catalyst.

13. A method according to claim 12, wherein the catalyst is p-toluene sulphonic 1 0 acid.

14. A method according to any of claims 10 to 13, wherein the lanolin fatty acid esters has an acid value <2mg KOH/g.

15 15. A method according to any of claim 10 to 14, wherein the lanolin fatty acid esters has an acid value <1 mg KOH/g.

16. A method according to any of claims 10 to 15, wherein the lanolin fatty acid esters have less than 15 carbon atoms per molecule.

17. A method according to any of claims 9 to 16, wherein the hydrogenation is carried out in the presence of a copper chromite catalyst.

18. A method according to any of claims 9 to 17, wherein the hydrogenation is 25 carried out at a temperature in the range of from 200 to 360 C.

19. A method according to claims 9 to 18, wherein the hydrogenation is carried out at a pressure in the range of from 17,000 to 31,000 kPa.

30

20. A composition according to any of claims 1 to 8 or preparable by a process according to any of claims 9 to 19, substantially free from lanolin ester.

21. A formulation comprising a lanolin-derivable composition according to any of claims 1 to 8 in association with a carrier therefor.

22. A formulation according to claim 21, in a form suitable for dermatological or topical administration.

23. A formulation according to claim 21 or 22, further comprising one or more 5 ingredients selected from: lanolin alcohols, lanolin acids, lanolin oils, lanolin waxes, lanolin acid soaps, lanolin esters, alkoxylated lanolins, hydrogenated lanolins, hydroxylated lanolins, quaternised lanolins and acylated lanolins.

24. A formulation according to any of claims 21 to 23, further comprising one or 10 more ingredients selected from: antiseptic compounds, emollients, inorganics, humectants, moisturizers, anti-inflammatory agents, vitamins, preservatives, pH adjusters, proteins, herbal extracts, solvents, soothing/cooling agents, perfumes, emulsifiers, viscosity modifiers, preservatives, dispersants, viscosity modifiers, herbal extracts, chelating agents, antioxidants and water-proofing agents.

25. The use of a lanolin-derivable composition according to any of claims 1 to 8 in the preparation of a formulation according to any of claims 22 to 24.

26. The use of a composition or formulation according to any of claims 1 to 24 in 20 the treatment or prevention of a disease or condition selected from: skin barrier damage, wounds, burns, granulated skin tissue, rough skin, trans-epidermal water loss, epithelial damage, dry skin, eczema and dermatitis.

27. The use of a composition or formulation according to any of claims 1 to 24 25 for the treatment or prevention of inflammation or inflammatory conditions.

28. The use of a composition or formulation according to any of claims 1 to 24 for the treatment or prevention of a microbial infection, including a S. aureus infection.

29. A formulation according to claim 21, in a form suitable for industrial, household or agricultural applications.

30. A formulation according to claim 21 or 29, further comprising one or more 35 ingredients selected from: lanolin alcohols, lanolin acids, lanolin oils, lanolin waxes, lanolin acid soaps, lanolin esters, alkoxylated lanolins, hydrogenated lanolins,

hydroxylated lanolins, quaternised lanolins, acylated lanollns, emollients, inorganics, humectants, preservatives, pH adjusters, proteins, herbal extracts, solvents, antioxidants, perfumes, emulsifiers, viscosity modifiers, preservatives, dispersants, detergents, surfactants, lubricants, agrochemical actives, anti-static agents, viscosity 5 modifiers, herbal extracts, chelating agents and water-proofing agents.

Amendments to the claims have been filed as follows _.. Claims 1. A composition formed from the reduction of lanolin or a lanolin-derived 5 feedstock, said composition comprising at least 25% w/w of lanolin hydrocarbons and at most 75% w/w lanolin alcohols, based on the total weight of the composition.

2. A composition according to claim 1, comprising at least 50% w/w of lanolin hydrocarbons. 3. A composition according to claim 1 or claim 2, comprising at least 75% w/w of lanolin hydrocarbons.

6. A composition according to any preceding claim, wherein the lanolin hydrocarbons each comprise in the range of from 8 to 40, such as 12 to 32 carbon atoms. 7. A composition according to any preceding claim, preparable by extended hydrogenation of lanolin fatty acid esters.

8. A composition according to claim 7, wherein the lanolin fatty acid esters are 30 obtainable by reaction of lanolin fatty acids with isopropyl alcohol.

35 10. A method according to claim 9, wherein the woolwax alcohols are obtainable by hydrogenation of lanolin fatty acid esters.

5 Is 1 2. A method according to claim 11, wherein the esterification reaction is -

undertaken in the presence of a catalyst.

13. A method according to claim 12, wherein the catalyst is p-toluene sulphonc 1 0 acid.

30. A formulation according to claim 21 or 29, further comprising one or more ingredients selected from: lanolin alcohols, lanolin acids, lanolin oils, lanolin waxes, lanolin acid soaps, lanolin esters, alkoxylated lanolins, hydrogenated lanolins, hydroxylated lanolins, quaternised lanolins, acylated lanolins, emollients, inorganics, 5 humectants, preservatives, pH adjusters, proteins, herbal extracts, solvents, Is antioxidants, perfumes, emulsifiers, viscosity modifiers, preservatives, dispersants, detergents, surfactants, lubricants, agrochemical actives, anti-static agents, viscosity modifiers, herbal extracts, chelating agents and water-proofing agents.

30 20. A composition according to any of claims 1 to 8 or preparable by a process according to any of claims 9 to 19, substantially free from lanolin ester.

21. A formulation comprising a lanolin-dervable composition according to any of --a claims 1 to 8 in association with a carrier therefor.

Is 22. A formulation according to claim 21, in a form suitable for dermatological or topical administration.

24. A formulation according to any of claims 21 to 23, further comprising one or 10 more ingredients selected from: antiseptic compounds, emollients, inorganics, humectants, moisturizers, anti-inflammatory agents, vitamins, preservatives, pH adjusters, proteins, herbal extracts, solvents, soothng/cooling agents, perfumes, emulsifiers, viscosity modifiers, preservatives, dispersants, viscosity modifiers, herbal extracts, chelating agents, antioxidants and water-proofing agents.

26. The use of a composition or formulation according to any of claims 1 to 8 20 inclusive or claims 20 to 24 inclusive in the preparation of a medicament for use in the treatment or prevention of a disease or condition selected from: skin barrier damage, wounds, burns, granulated skin tissue, rough skin, trans-epidermal water loss, epithelial damage, dry skin, eczema and dermatitis.

25 27. The use of a composition or formulation according to any of claims 1 to 8 inclusive or claims 20 to 24 inclusive in the preparation of a medicament for use in the treatment or prevention of inflammation or inflammatory conditions.

28. The use of a composition or formulation according to any of claims 1 to 8 30 inclusive or claims 20 to 24 inclusive in the preparation of a medicament for use in the treatment or prevention of a microbial infection, including a S. aureus infection.