WO2014015881A2

WO2014015881A2 - A cosmetic or medical composition with kigelia africana

Info

Publication number: WO2014015881A2
Application number: PCT/DK2013/050253
Authority: WO
Inventors: Jan WAAGE; Allan Kim Gercke MALMDORF; Bo Ritsmar PEDERSEN
Original assignee: KIMOVI APS
Current assignee: KIMOVI APS
Priority date: 2012-07-25
Filing date: 2013-07-25
Publication date: 2014-01-30
Anticipated expiration: 2015-01-25
Also published as: WO2014015874A1; EP2877250A2; EP2877191A1; WO2014015881A3; EP2877191A4

Abstract

The present invention relates to a cosmetic or medical composition for topical application on the skin of a subject, which composition comprises: brine 40 - 80 %w/w an extract of Kigelia africana 2 - 15%w/w one or more excipients 5 - 50%w/w water balance which excipients are selected from emulsifiers, suspending agents, gelling agents, binders, fillers, surfactants, anti-oxidants, preservatives, emollients, humectants, moisturisers, natural oils, UV-absorbers, sunscreens, and thickeners. The composition is suitable for use in the treatment of skin damages, diseases and conditions.

Description

A cosmetic or medical composition with Kigelia africana Field of the invention

The present invention relates to a cosmetic or medical composition for topical application on the skin of a subject, which composition comprises an extract of K. africana. The composition is suitable for use in the treatment of skin damages, diseases and conditions. The composition provides a longer lasting effect of the activities of K. africana.

Background In general the use of extracts and other products from the plant Kigelia africana for the treatment of skin diseases and conditions is well known. For example, WO 2006/002443 describes pharmaceutical and cosmetic preparations based on K. africana. The preparations of WO 2006/002443 may be in the form of a cream, ointment or gel, and it is intended as a general pain reliever, an anti-septic, an anti-inflammatory or an anti-pruritic. Specific applications are for the treatment of cuts, bruises, insect bites, stings, sun exposure of the skin, psoriasis, eczema, solar keratosis, and cancerous sores.

FR 2 759 910 also describes cosmetic compositions for skin care and body care containing extracts of K. africana. These may be used for firming of the bust, limiting hair loss, and limiting hair growth. Further skin creams of K. africana are provided by ZW 10292.

The constituents of K. africana, their extraction and known medical effects are described in Kigelia africana (Lam.) Benth - An overview, S. Saini, H. Kaur, B. Vherma, Ripudaman, S. K. Singh, 2009, Nature Product Radiance, 8: 190-197, and Comprehensive scientific demystification of Kigelia africana : A review, Olatunji A. Gabriel and Atolani Olubunmi, 2009, African Journal of Pure and Applied Chemistry, 3: 158-164. Saini et a/., 2009, describe how an ethanol extract was tested for pharmacological activity in animal studies in mice and in cell lines. It was concluded from the tests that ethanolic extracts of K. Africana have a significant positive effect on use against skin irritation / oedema and a significant antibacterial/ antimicrobial inhibitory effect on both Gram-positive and Gram-negative bacteria There is however still a need for further and improved products relying on the medical and cosmetic activities of K. africana. In particular, there is a need for products providing a longer lasting effect of the activities of K. africana. It is the aim of the present invention to provide improved medical and cosmetic compositions for delivery of K. africana extracts.

Summary of the invention

The present invention relates to a cosmetic or medical composition for topical application on the skin of a subject, which composition comprises: brine 40 - 80 %w/w

an extract of Kigelia africana 2 - 15 %w/w

one or more excipients 5 - 50 %w/w

water balance

which excipients are selected from emulsifiers, suspending agents, gel- ling agents, binders, fillers, surfactants, anti-oxidants, preservatives, emollients, humectants, moisturisers, natural oils, UV-absorbers, sunscreens, and thickeners.

The present inventors have now surprisingly found that the composition of the invention is advantageous for the delivery of the active ingredient of an extract of K. africana. Thus, the effects of an extract of K. Africana, e.g. an ethanolic extract, on skin diseases and conditions, such as psoriasis, eczemas, dermatitis, and acne are advantageously longer lasting when applied in combination with the salts and minerals from the brine. For example, by applying the composition, e.g. as a gel or cream, to the skin of a subject suf- fering from psoriasis, the psoriasis significantly turns into more relaxed skin after 2-3 applications in 3 days, and after 5-6 days of treatment the skin stops itching. Moreover, it has surprisingly been found that the extract of K. Africana and the brine act synergistically so that the effect can be said to be stronger than when either of the brine or the extract of K. Africana are ap- plied individually. The cosmetic or medical composition may be a cream, gel, ointment, lotion or paste. It is also contemplated that the extract of K. africana may be replaced with any other active ingredient and that the advantages of obtaining a longer lasting effect may also be realised for other active ingredients so that the composition of the invention is suitable for transdermal delivery of any active ingredient.

Any extract of K. africana may be used in the present invention. It is preferred that the extract is an ethanolic extract from the fruits of the plant. The cosmetic or medical composition of the invention provides a longer lasting effect of the active compounds of K. africana, than is obtainable when a K. africana extract is applied in a formulation without brine or directly onto the skin. Furthermore, the cosmetic or medical composition also provides a stronger effect of the extract of K. africana.

Brine, e.g. in the form of thermal water, is known from its positive effects to damaged skin, and to drive other active ingredients into the skin's layers and pores. In particular, when the brine is a thermal water salts and minerals, e.g. other than NaCI, are advantageous to the skin. This effect will also be observed when the brine is derived from e.g . sea water which has been evaporated to saturation of NaCI. In combination with the known positive effects from K. africana the resulting mixture produces the unique properties to the transportation of the active compounds from the surface of the skin and into the pores of the skin. Without being bound by theory it is believed that the effect, e.g. the moisturising action, from the composition is longer lasting because of the effects of the salts of the brine as a hydrating agent. Appropriate thermal waters are those emerging from a depth of 800 meters from Central Europe, such as those ava ila ble from Sulbeck (Germany), where the geothermal temperatures constantly is 20°C (22.1°C per km of depth or 1°F per 70 feet of depth). The saturated brine generally con- tains about 26% sodium chloride (NaCI) and a range of different minerals. For example, thermal waters from Sulbeck comprise, in addition to sodium chloride, also magnesium, potassium, sulphate, iron, selenium, iodine, bromine and sulphur.

The cosmetic or medical composition of the invention may be formu- lated as a cream or as a gel. When formulated as a cream the composition comprises from 2 to 8 %w/w extract of K. africana, from 40 to 60 %w/w brine and from 30 to 40 %w/w excipients. When formulated as a gel the composition comprises from 5 to 15 %w/w extract of K. africana, from 60 to 80 %w/w brine and from 5 to 15 %w/w excipients, which comprise a gelling agent, e.g. xanthan gum. The excipients may be any excipients, in particular excipients known to the skilled person for formulating the composition as a cream or gel, respectively. In a preferred embodiment the cosmetic or medical composition comprises a gelling agent at a concentration in the range of from 0.1 %w/w to 10%w/w; any gelling agent may be used in the invention. Thus, in a preferred embodiment the cosmetic or medical composition is a gel comprising :

brine 70 %w/w

an extract of K. africana 10 %w/w

glycerin 5 %w/w

propylene glycol 2 %w/w

gelling agent 1 %w/w

water balance.

The gelling agent may be selected from agar, carrageenan, gelatine, pectin, xanthan gum, gum arabic, guar gum, locust bean gum, and alginate or a combination thereof. A preferred gelling agent is xanthan gum.

The extract, e.g. an ethanolic extract, from K. Africana, e.g. the fruit, shows a significant effect on treatment skin diseases and conditions, such as psoriasis, eczemas, dermatitis and acne. The cosmetic or medical composition of the invention is suitable for application to the skin of a subject, e.g. a hu- man subject, in order to provide the effect of the K. africana extract to the skin of the subject. When the cosmetic or medical composition is formulated as a gel the present inventors have found that the gelling agent further improves the synergistic effects of the combination of high salt concentration and the active compounds of K. africana. Without being bound by theory it is believed that the gelling agent may be considered as a carrier for the K. africana extract and allowing the active compounds of K. africana to diffuse to the skin of the subject and working synergistically with the high salt content. In particular, the gelling agent may absorb moisture from damaged skin forming a thin layer of a liquid gel over the damaged skin resulting in delivery of the K. africana extract to the damaged skin with an enhancement provided by the salt. The gelling agent is believed to provide that the K. africana extract is kept in place on the skin. Thus, the combined effects of the gelling agent, e.g. the aqueous nature of the gel and the brine allow a long-term diffusion of the active compounds of K. africana to the skin of the subject where the gel composition is applied. Such a long-term effect cannot readily be obtained when the K. africana extract is applied directly to the skin. The composition of the invention may be used in the treatment of any inflammatory skin disorder; when used against inflammatory skin disorders the composition minimises, or even removes, the need for steroid based treatment and the side effects accompanying steroid treatment can thereby be minimised or avoided.

It is also contemplated that the effect obtained from the combination of salt and K. africana extract, especially when combined with a gelling agent, is generally applicable to other active ingredients.

In a specific embodiment the composition is a cream comprising :

brine 50 %w/w

an extract of K. africana 5 %w/w

octyldodecyl stearate 10 %w/w

cetyl alcohol 8 %w/w

glycerine 4.2 %w/w

dicaprylyl carbonate 2.5 %w/w

lauryl polyglucose 2 %w/w

cera alba 2 %w/w

PEG-50 Shea butter 1.25 %w/w

glycerol stearate 1 %w/w

PEG-75 Stearate 1 %w/w

ceteth-20 1 %w/w

steareth-20 1 %w/w

polyg lycery I - 2 d i poly hyd roxystea rate 0.5 %w/w

tocopherol 0.15 %w/w

allantoin 0.13 %w/w

water balance.

The cosmetic or medical composition of the invention is suitable for use in the treatment of skin damages, diseases and conditions, such as pso- riasis, eczemas, dermatitis, acne, especially any inflammatory skin disorder. Thus, in an embodiment of the invention the composition is for use in medicine, e.g. in the treatment of skin damages, diseases and conditions. Specific examples of the diseases and conditions are psoriasis, eczemas, dermatitis or acne. In another embodiment of the invention the composition is for cosmetic use. Brief description of the figures

The invention will be readily understood from the following detailed description in conjunction with the accompanying figure, in which

Figure 1 shows photographs of the skin of a subject suffering from psoriasis before and after treatment with a composition of the invention.

Figure 2 shows photographs of the skin of a subject suffering from nappy rash before and after treatment with a composition of the invention.

Figure 3 shows photographs of the skin of a subject suffering from psoriasis before and after treatment with a composition of the invention.

Figure 4 shows photographs of the skin of a subject suffering from hand lesions before and after treatment with a composition of the invention.

Figure 5 shows photographs of the skin of a subject suffering from rosacea before and after treatment with a composition of the invention.

Figure 6 shows photographs of the skin of a subject suffering from acne before and after treatment with a composition of the invention.

Figure 7 shows photographs of the skin of a subject suffering from acne before and after treatment with a composition of the invention. Detailed description of the invention

In order to more fully explain the invention it is disclosed in more detail below, and definitions of the terms used throughout the document are given. The present invention relates to a cosmetic or medical composition for topical application on the skin of a subject, which composition comprises: brine 40 - 80 %w/w

an extract of Kigelia africana 2 - 15 %w/w

one or more excipients 5 - 50 %w/w

water balance

The term "extract" should be understood broadly and the extract may be prepared using any solvent or supercritical solvent. The "extract" is not limited to a liquid form but also comprises the residue provided from a liquid extract after removal of the solvent. In general, an extract is prepared by providing a part of a K. africana plant, e.g. fruits, leaves, bark, stem bark, root bark etc., and contacting the plant part with a solvent or supercritical solvent. Prior to extraction, the plant part may be cut into smaller pieces and/or be disrupted to increase the extraction efficiency. The extraction may also comprise any other processing step. For example, the plant part may be dried before extraction. In a specific embodiment the fruit of the K. Africana tree is cut into smaller pieces, which are dried in a ventilated oven at 75°C for approximately 48 hours before pulverising the smaller pieces. One part pulverised fruit is then mixed with 10 parts 30% ethanol in water solution, stirred overnight and filtered. The brown water/ethanol phase is spray-dried using maltodextrin as a matrix. The spray dried extract can be used directly in the products of the invention or it can be reconstituted in a solvent for use in the invention. In general, the extractant may be selected from its polarity in order to selectively extract components of the plant part; appropriate solvents and corresponding components are provided by Saini et al., 2009 and Gabriel et al., 2009 which are hereby incorporated by reference. An ethanolic extract of the fruits is preferred. In certain embodiments, the solvent is re- moved from the extract so that the extract is employed in a dry form. For the cosmetic or medical product of the invention the extract may be in a dry form or the extract may be in a liquid form. The liquid form may be the extract obtained from the K. africana plant part, e.g. 30% ethanol in water, without spray drying or the liquid form may be reconstituted from a spray dried ex- tract. It is also possible to modify an extract obtained from the K. africana plant part, e.g. when the extract is prepared using 30% ethanol in water the ethanol concentration may be increased, e.g. to 70%. In general, the content of K. africana extract is expressed in percent by weight (%w/w). This percentage is thus the dry matter content of the K. africana extract, e.g. as measured after spray drying a liquid extract, relative to the total mass of the composition. The extract need not be spray dried in order to estimate the dry matter content, and other methods of estimating the dry matter content are known to the skilled person. When the extract is employed in a liquid form the viscosity of the extract may be raised or lowered, e.g. by addition of gly- col or ethanol, respectively, to the extract, to bring the viscosity within the range of from about 1 to 50 mPas, e.g. about 10 mPas. The viscosity may also be outside these ranges. The extract may also be filtered, e.g. through a 0.45 μηι or 0.2 μηι filter.

The extract of K. africana may also be referred to as an "active ingre- dient". The extract of K. africana is not limited to bulk extract but may also be a purified single active compound from K. africana. The terms "active ingredient" and " C. africana extract" may be used interchangeably. The active ingredient may also comprise any other pharmaceutically or pharmacologically active agent or a natural remedy or a plant extract. The presence of the active ingredient, e.g. compounds from K. africana, in the cosmetic or medical composition provides that the active ingredient is delivered to the skin. The cosmetic or medical composition may be suitable for application on any part of the subject's skin. The cosmetic or medical composition may be used in the treatment of skin damages, diseases and conditions, e.g . psoriasis, eczemas, dermatitis or acne. The cosmetic or medical composition of the invention is suitable for use in the treatment of psoriatric arthritis or rheumatoid arthritis. Further conditions that may be treated with the composition of the invention comprise prurigo nodularis, atopic dermatitis, contact dermatitis, actinic keratosis, nappy rash, rosacea or general skin lesions.

Exemplary gelling agents are selected from agar, carrageenan, gelatine, pectin, xanthan gum, gum arabic, guar gum, locust bean gum, and alginate or a combination thereof. The gelling agent may also be any mixture of these components, and the gelling agent may also comprise other components, e.g. excipients or the like. The invention relates to a cosmetic or medi- cal composition comprising the extract of K. africana and a brine, in particular a brine derived from a thermal water. In the context of the present invention the term "brine" refers to a saturated aqueous salt solution. The salt is preferably mineral salt or sea salt, and the major cationic component of the brine is thus sodium ions, and the major anionic component is chloride ions. Other ionic components may be sulphate, magnesium, calcium, potassium, bicarbonate, bromide, borate, and strontium. In certain embodiments the brine is provided by concentrating seawater or saline groundwater. For example sea- water or saline groundwater may be heated to evaporate water and to precipitate salts; separation of the precipitated salts will provide the brine. In a specific embodiment the relative contents of sodium and chloride in solution are lowered compared to the starting material, e.g. sea water, so that the brine will be enriched in other ions, while being saturated in the major components, e.g. sodium and chloride ions. In another embodiment, the brine is a "thermal water" derived from geothermal heated groundwater, in particular from groundwater with a high mineral and/or salts content. In general, the brine, e.g. as a saturated solution, comprises about 26% NaCI.

In the context of the invention an "excipient" is any generally pharmacologically inactive substance used as an aid in the formulation of the cosm et i c o r m ed i ca l co m p os i t i o n , o r w h i c h p rov i d e s a n ot h e r n o n- pharmacologically related function to the composition. Any excipient providing a desired functionality may be employed in the composition of the invention. The cosmetic or medical composition may comprise one or more excipi- ents selected from emulsifiers, suspending agents, gelling agents, binders, fillers, surfactants, anti-oxidants, preservatives, emollients, humectants, moisturisers, natural oils, UV-absorbers, sunscreens, and thickeners. Excipi- ents are well-known to the skilled person, e.g. from the European Pharmacopoeia.

The cosmetic or medical composition is preferably formulated as a cream or a gel. A "cream" is a topical preparation for application to the skin generally consisting of an emulsion of an oil phase and a water phase with an appropriate emulsifier. When the composition is formulated as a cream it can be considered to be an oil-in-water emulsion. A "gel" is an aqueous composition comprising a gelling agent, which may be a hydrophilic polymer, allowing formation of a viscous solution or suspension. Th us, a crea m ca n be de- scribed as "greasy" and the gel can be described as "dry". A greasy cream is especially advantageous when applied to the skin of a subject suffering from dermatitis or psoriasis since the cream will strengthen and restore the lipids in the epidermis which will strengthen the barrier characteristics of the skin. A dry gel is especially advantageous when applied to the skin of a subject suffering from acne since the gel will form a thin layer on the skin and provide the effects of the brine and the extract of K. africana. The advantages of the dry gel are also relevant for a subject suffering from psoriasis. The composition of the invention may be applied to any part of the skin of a subject, e.g. to skin near or at the subject's joints. The invention is now described in the following non-limiting examples. The examples represent case studies that illustrate the effects of the invention. Examples

Example 1

A composition of the invention in the form of a gel was prepared. The gel comprised :

brine 70 %w/w

an extract of K. africana 10 %w/w

glycerin 5 %w/w

propylene glycol 2 %w/w

gelling agent 1 %w/w

water balance.

The gel was tested on a subject suffering from psoriasis. A typical way of treatment of psoriasis damaged skin : 2-3 times of daily application of the gel containing K. africana and brine. The gel provides a thin protecting layer with a significant improving result discovered through a number of tests on psoriasis patients. The brine is known to give the protecting layer effect on skin, and in combination with the described positive effects from K. africana achieves a better treatment than could be obtained with either brine or K. africana alone, where the active compounds obtain a longer and more effective contact to skin. The pictures in Figure 1 show the results before and after 3 weeks of treatment (3 x applications per day in 21 days) of a psoriasis damaged skin on a left foot. The picture in Figure la shows the untreated skin, and the picture in Figure lb shows the result after 21 days of treatment. The patient concluded that the level of irritation and itching was significantly bettered using the gel containing K. africana and brine compared to his experience with products only containing brine. This patient describes positive effects after the first 3 times of application. This example is representative for all the conducted tests in this group of patients. Example 2

A composition of the invention in the form of a cream was prepared.

The cream comprised :

brine 50 %w/w

an extract of K. africana 5 %w/w

octyldodecyl stearate 10 %w/w

cetyl alcohol 8 %w/w

glycerine 4.2 %w/w

dicaprylyl carbonate 2.5 %w/w

lauryl polyglucose 2 %w/w

cera alba 2 %w/w

PEG-50 Shea butter 1.25 %w/w

glycerol stearate 1 %w/w

PEG-75 Stearate 1 %w/w

ceteth-20 1 %w/w

steareth-20 1 %w/w

polyglyceryl-2 dipolyhydroxystearate 0.5 %w/w

tocopherol 0.15 %w/w

allantoin 0.13 %w/w

water balance.

A typical way of using the cream containing K. africana and brine: The product was applied on the irritated skin 2-3 times per day or as needed.

Compared to products only containing brine the test on patients conclude, that the combination of K. africana and brine gives a significant healing ef- feet. The itching stops after 1-2 applications and this effect continued as long as the product was applied.

Example 3

A child suffering from nappy rash was treated with a cream of the invention. Figure 2 (left panel) shows a photograph of the skin before treatment and after treatment (right panel). The treatment resulted in removal of the nappy rash. Example 4

A woman with lesions on her fingers was treated with a cream of the invention. Figure 3 (left panel) shows a photograph of the skin before treatment and after treatment (right panel). The treatment resulted in complete healing of the lesions.

Example 5

A woman suffering from rosacea was treated with a cream of the invention. Figure 4 (left panel) shows a photograph of the skin before treat- ment and after treatment (right panel). After one week's treatment the red zones around the eyes had disappeared. The subject further reported that swelling around the joints of her hands caused by rheumatoid arthritis were diminished due to the treatment. Example 6

A 43 year old woman suffering from psoriasis applied the gel of the invention on her scalp. After 10 days of treatment the lesions had disappeared. Figure 5 (left panel) shows a photograph of the skin before treatment and after treatment (right panel). The subject reported that repeated treatment with the gel allowed her to keep the symptoms under control without any side effects.

Example 7

Two subjects, a 17 year old girl and a 25 year old man applied the gel of the invention to acne on their chest, back and shoulders. Both reported significant improvements in the removal of their symptoms after two to three weeks of treatment. Figure 6 illustrates the skin of the first subject after three weeks of treatment (left panel) compared to the skin before treatment (right panel). Figure 7 illustrates the skin of the second subject before treat- ment (left panel) and after two weeks of treatment (right panel). The second subject reported that the gel of the invention could replace broad spectrum antibiotic treatment and its concomitant side effects. Example 8

A man suffering from recurring eczema on the wrist of his hand applied the gel of the invention to the eczema. After four days of twice daily treatment the eczema had disappeared. In comparison, the subject reported that treatment with hydrocortisone cream required 4-5 weeks of treatment and caused undesirable side effects.

Claims

P A T E N T C L A I M S

1. A cosmetic or medical composition for topical application on the skin of a subject, which composition comprises:

brine 40 - 80 %w/w

an extract of Kigelia africana 2 - 15 %w/w

one or more excipients 5 - 50 %w/w

water balance

2. The cosmetic or medical composition according to claim 1, wherein the cosmetic or medical composition is a cream, gel, ointment, lotion or paste.

3. The cosmetic or medical composition according to claim 1 or 2, wherein the cosmetic or medical composition is a cream comprising :

brine 40 - 60 %w/w

an extract of K. africana 2 - 8 %w/w

one or more excipients 30 - 40 %w/w

water balance.

4. The cosmetic or medical composition according to claim 3, wherein the cosmetic or medical composition is a cream comprising :

brine 50 %w/w

an extract of K. africana 5 %w/w

octyldodecyl stearate 10 %w/w

cetyl alcohol 8 %w/w

glycerine 4.2 %w/w

dicaprylyl carbonate 2.5 %w/w

lauryl polyglucose 2 %w/w

cera alba 2 %w/w

PEG-50 Shea butter 1.25 %w/w

glycerol stearate 1 %w/w

PEG-75 Stearate 1 %w/w

ceteth-20 1 %w/w steareth-20 1 %w/w

polyglyceryl-2 dipolyhydroxystearate 0.5 %w/w

tocopherol 0.15 %w/w

allantoin 0.13 %w/w

water balance.

5. The cosmetic or medical composition according to claim 1 or 2, wherein the cosmetic or medical composition is a gel comprising :

brine 60 - 80 %w/w

an extract of K. africana 5 - 15 %w/w

one or more excipients 5 - 15 %w/w

water balance,

wherein the excipients comprise a gelling agent.

6. The cosmetic or medical composition according to claim 5, wherein the cosmetic or medical composition comprises a gelling agent at a concen- tration in the range of from 0.1 %w/w to 10%w/w.

7. The cosmetic or medical composition according to claim 5 or 6, wherein the gelling agent is selected from agar, carrageenan, gelatine, pectin, xanthan gum, gum arabic, guar gum, locust bean gum, and alginate or a combination thereof.

8. The cosmetic or medical composition according to any one of claims

5 to 7, wherein the cosmetic or medical composition is a gel comprising :

brine 70 %w/w

an extract of K. africana 10 %w/w

glycerin 5 %w/w

propylene glycol 2 %w/w

gelling agent 1 %w/w

water balance.

9. The cosmetic or medical composition according to claim 8, wherein the gelling agent is xanthan gum.

10. The composition according to any one of claims 1 to 9 for use in the treatment of skin damages, diseases and conditions.

11. The composition according to claim 10, wherein the disease or condition is psoriasis, eczemas, dermatitis or acne.

12. The composition according to any one of claims 1 to 9 for cosmetic use.