WO2007039149A1

WO2007039149A1 - Method and composition comprising squalane and / or squalane for treating burn

Info

Publication number: WO2007039149A1
Application number: PCT/EP2006/009243
Authority: WO
Inventors: Franciscus Johannes Groenhof; Johann Wilhelm Wiechers
Original assignee: Unichema Chemie B.V.
Priority date: 2005-09-22
Filing date: 2006-09-22
Publication date: 2007-04-12
Also published as: GB0519334D0

Abstract

Methods of treating skin damaged by heat and/or radiation using a composition containing squalane and/or squalene. The composition preferably has an occlusivity of 50 to 80 %, and is preferably applied to the skin at a temperature above 0 °C. Increased speed of recovery of the skin, greater re-growth of hair, reduction in scar tissue formation and/or less discolouring of the skin may occur.

Description

METHOD AND COMPOSITION COMPRISING SQUALANE AND / OR SQUALENE FOR TREATING BURN

Field of Invention

5 The present invention relates to compositions and methods of treating skin damaged by heat and/or radiation.

Background

10 There is a constant need to improve the treatment of burns, in particular to speed up the healing of a burn both for cosmetic effects, as well as for the health and/or comfort of the recipient of the burn during the treatment. Existing treatments normally involve application of an antibacterial and a barrier cream such as white petrolatum. However, problems with prior art barrier creams include that they can be

15 painful to apply and remove, and the newly generated skin may not develop properly such that scar tissue and skin discolouration may form and/or there may be little or no re-growth of hair.

Squalane and squalene are triterpenes, and may be natural or synthetic products.

20 Squalane and squalene are present in the bodies of all fish, and may be extracted, for example, from the liver oil of deep-sea shark. Squalene is an unsaturated triterpene and it may be converted to saturated squalane by hydrogenation, e.g. by using a nickel catalyst. Squalane may also be produced synthetically by the coupling of two molecules of geranyl acetone with diacetylene, followed by dehydration and

25 complete hydrogenation; or by the dimerization of dehydronerolidol, followed by dehydration and hydrogenation. Squalane can also be extracted in a multi-step process from vegetable oils, such as olive oil.

Prior Art

30

JP-53079036-A describes the use of squalene as a bactericide and drug for the treatment of skin diseases. The squalene is taken orally, or applied as an ointment with white petrolatum. EP-O457193-A describes the use of squalane or squalβnβ as a cooling treatment immediately after a burn.

Summary of the Invention

We have now surprisingly discovered methods of treating skin damaged by heat and/or radiation which reduces or substantially overcomes at least one of the aforementioned problems.

Accordingly, the present invention provides the use of squalane and/or squalene in the preparation of a medicament having an occlusivity in the range from 50 to 80% for the topical treatment at a temperature of greater than O⁰C of a bum.

The invention also provides a method of treating burnt or damaged skin by topically applying, at a temperature of greater than O⁰C, a composition having an occlusivity in the range from 50 to 80% comprising squalane and/or squalene.

The invention further provides the use of squalane and/or squalene in the preparation of a medicament for the topical treatment of a burn wherein the medicament is applied subsequent to the topical application of an antimicrobial.

The invention further provides the use of squalane and/or squalene and an antibacterial in the preparation of a medicament for topical treatment of a burn, said medicament comprising squalane and/or squalene, and antibacterial in separate compositions with the squalane/squalene composition being administered subsequent to the antimicrobial composition.

The invention further provides a method of topically treating skin comprising (i) firstly applying a composition comprising an antimicrobial, and (ii) subsequently applying a composition comprising squalane and/or squalene.

The invention further provides the use of squalane and/or squalene in the preparation of a medicament having an occlusivity in the range from 50 to 80% for the topical treatment of a burn, said medicament being applied greater than 24 hours after receiving the burn. The invention further provides the use of squalane and/or squalene in the preparation of a medicament for the topical treatment of skin subjected to radiation during treatment for cancer.

The invention yet further provides a composition having an occlusivity in the range from 50 to 80% comprising squalane and/or squalene and an antimicrobial.

The composition used in the present invention suitably comprises in the range from 60 to 100%, preferably 75 to 100%, more preferably 95 to 100%, particularly 99 to 100%, and especially substantially 100% by weight of the composition of squalane and/or squalene, preferably of squalane.

Natural or synthetic squalane and/or squalene may be used in the present invention, but natural products, particularly squalane extracted from vegetable oil, especially olive oil, are preferred.

In a preferred embodiment, the composition preferably comprises less than 10%, more preferably less than 5%, particularly less 1%, and especially substantially 0% by weight of the composition of water.

The composition preferably has an occlusivity (measured as described herein) in the range from 50 to 80%, more preferably 55 to 70%, particularly 57 to 62%, and especially 58 to 60%.

The composition preferably has a melting point (measured as described herein) of less than 0⁰C, more preferably in the range from -10 to -80⁰C, particularly -20 to -45°C, and especially -36 to -40⁰C.

The composition suitably has a moderate substantivity, preferably having a value in the range from 10 to 50%, more preferably 15 to 40%, particularly 18 to 30%, and especially 20 to 23% (measured as described herein).

The composition preferably comprises less than 1000, more preferably less than 100, particularly less than 10, and especially 0 (i.e. sterile) colony forming units (cfu's) cm'³. The composition is preferably applied to the skin at a concentration in the range from 0.001 to 10, more preferably 0.05 to 5, particularly 0.5 to 3, and especially 0.7 to 2 mg cm'².

The composition is suitably applied to the skin at a temperature above 0⁰C₁ preferably in the range from 10 to 40⁰C, more preferably 15 to 39°C, particularly 17 to 38⁰C, and especially 20 to 37°C.

The composition described herein is suitable for applying to skin which has been burnt or damaged by chemicals (irritants, acids or alkalis), fire or heat (burns or spillage of hot liquids such as cooking oils and fats, or drinks), by radiation such as excessive exposure to the sun (UV rays), or radiotherapy in the treatment of cancer, preferably skin cancer.

Particularly for the treatment of second or third degree burns, the composition is preferably firstly applied to the skin greater than 24, more preferably greater than 36, and particularly greater than 48 hours after receiving the bum. The composition is preferably applied, usually twice a day, for a period of 1 to 21 , more preferably 4 to 18, and particularly 7 to 14 days, dependent upon the severity of the bum.

The composition is preferably applied after initial treatment of the second or third degree bum (up to the first 48 hours) with an antimicrobial, preferably an antibiotic, particularly silver sulphadiazine (for example sold under the trade name Flammazine). The antimicrobial and/or antibiotic is preferably applied to damaged skin in an ointment at a concentration in the range from 0.01 to 10%, more preferably 0.1 to 5%, particularly 0.5 to 2%, and especially 0.8 to 1.2% by weight. Thus, the squalane/squalene composition is preferably applied subsequent to the application of an antimicrobial composition.

Alternatively, the squalane/squalene composition may contain the antimicrobial and/or antibiotic described above, preferably at a concentration in the range from 0.01 to 10%, more preferably 0.1 to 5%, particularly 0.5 to 2%, and especially 0.8 to 1.2% by weight. Thus, the application of the squalane/squalene and antimicrobial/antibiotic may be combined, in which case the composition would be suitably applied as soon as possible after the burn, preferably for 0 to 21 , more preferably 0 to 18, and particularly 0 to 14 days after receiving the bum.

In a further embodiment, the squalane/squalene and antimicrobial composition described above is applied for up to 2 days after receiving the bum, followed by the squalane/squalene composition (without antimicrobial) which is preferably applied, usually twice a day, for a period of 1 to 21 , more preferably 4 to 18, and particularly 7 to 14 days.

The squalane/squalene composition may also contain other known therapeutic, preferably oil-soluble, materials, used for the local treatment of skin, such as skin moisturizers and viscosity improvers.

The use of the composition described herein may surprisingly result in increased speed of recovery, greater re-growth of hair, a reduction in scar tissue formation and/or less discolouring of the skin.

In this specification the following test methods have been used.

(i) Occlusivitv

The in-vitro occlusivity test method is based on the relative weight loss from a non- porous plastic cup (diameter of 3.5 cm), which was filled with 7 g of tap water, and closed by a porous Spectra/Por 5 membrane (a regenerated cellulose membrane combined with a paper reinforcement, ex. Spectra). The membrane which acts as a skin model, was bonded to the cup with Syncol 532 (ex. Swift Adhesives,

Netherlands). 0.03 g of the test product or composition was evenly coated over the entire surface of the membrane using a glass rod. The cup was placed in a climate room maintained at 23°C and 50% relative humidity. The weight loss after 3 hours was determined, compared with uncoated blank, and expressed as a relative percentage value (no weight loss = 100%, weight loss the same as control = 0%). Mean values of triplicate experiments were calculated.

_«/ . . . I , average weight loss test product Λ , _ΛΛΛy

% occlusivity = 1 - - x 100%

^ average weight loss blank J (ih Melting Point

The melting point was measured according to A.O.C.S. Official Method, TMa-64 (1989).

(iii) Substantivitv Substantivity on 20 subjects was measured by applying 1.84 mg cm^*2 of the test product or composition on untreated skin and leaving this in place for a set period of time. After 1 hour, the amouπft of oil was measured on the skin using a Sebumeter (Courage & Khazaka, Cologne, Germany) and the amount remaining on the skin quantified against a calibration curve using known quantities of the same material. Values were expressed as the percentage of material present relative to those remaining on Vaseline Petroleum Jelly treated skin (positive control, = 100%) and untreated skin (negative control, = 0%). Mean values of triplicate experiments were calculated for each subject, and a median value calculated for the 20 subjects.

The invention is illustrated by the following non-limiting example.

Example

Vegetable squalane (Pripure 3759 (trade mark, ex Uniqema)) was subjected to the test procedures described herein and exhibited the following properties;

(i) Occlusivity = 59.2%. (ii) Melting point = -38.1 ^βC.

(iii) Substantivity = 22.6% (minimum = 5.0%, maximum = 37.3%). Skin substantivity decreased as a function of time (30 min = 33.2%, 2 hours = 13 .6% and 4 hours = 6.5%), indicating that the vegetable squalane penetrates the skin more rapidly than the control (Vaseline Petroleum Jelly).

A subject suffered a burn (hot chemical spillage) which was treated with Flammazine (silver sulphadiazine) and subsequently with sterile Vaseline Petroleum Jelly. Daily wound care was painful. A few days later the subject was treated with 5 millilitres of vegetable squalane (Pripure 3759, ex Uniqema) applied to a sterile gauze pad which was dabbed on the wound and then dressed. This squalane was applied twice daily. After 4 days of squalane treatπaent the appearance of the burn greatly improved and continued to improve after one week of treatment. Squalane treatment was continued for a further week when even regrowth of hairs was visible. The squalane treatment was painless and the healing process was remarkably complete and fast.

The above example illustrates the improved properties of the present invention.

Claims

1. The use of squalane and/or squalene in the preparation of a medicament having an occlusivity in the range from 50 to 80% for the topical treatment at a temperature of greater than O⁰C of a bum.

2. A method of treating burnt or damaged skin by topically applying, at a temperature of greater than O⁰C₁ a composition having an occlusivity in the range from 50 to 80% comprising squalane and/or squalβne.

3. A method according to claim 2 wherein the method is cosmetic.

4. The use of squalane and/or squafβnβ in the preparation of a medicament for the topical treatment of a bum wherein the medicament is applied subsequent to the topical application of an antimicrobial.

5. The use according to claim 4 wherein the bum is a second or third degree bum.

6. The use of squalane and/or squalene and an antibacterial in the preparation of a medicament for topical treatment of a bum, said medicament comprising squalane and/or squalene, and antibacterial in separate compositions with the squalanβ/squalβnβ composition being administered subsequent to the antimicrobial composition.

7. The use according to claim 6 wherein the antimicrobial comprises silver suSphadiazine.

8. A method of topically treating skin comprising (i) firstly applying a composition comprising an antimicrobial, and (ii) subsequently applying a composition comprising squalane and/or squalene.

9. The use of squalane and/or squalene in the preparation of a medicament having an occfuslvity in the range from 50 to 80% for the topical treatment of a bum, said medicament being applied greater than 24 hours after receiving the bum.

10. The use of squalanβ and/or squalen© In the preparation of a medicament for the topical treatment of skin subjected to radiation during treatment for cancer.

11. A composition having an occlusivity in the range from 50 to 80% comprising squalanβ and/or squalβnβ and an antimicrobial.

12. A composition according to claim 11 wherein the antimicrobial is silver sulphacJiazine.