WO2005007127A1

WO2005007127A1 - Preparation to combat the unsightly skin effects of cellulite

Info

Publication number: WO2005007127A1
Application number: PCT/IB2004/002242
Authority: WO
Inventors: Daniela Montanari; Manuela Guglielmo
Original assignee: Gecomwert Anstalt
Priority date: 2003-07-21
Filing date: 2004-07-05
Publication date: 2005-01-27
Also published as: CH693819A5

Abstract

A preparation for topical use in any form and/or consistency for reducing or eliminating skin defects due to cellulite, whose composition comprises: d) Coenzyme A, e) Bupleurum falcatum extract, f) Horse Chestnut extract is described.

Description

Preparation to combat the unsightly skin effects of cellulite .

This invention relates to the field of cosmetic preparations for topical use of any kind and consistency (oils, pastes, creams, gels, emulsions, aqueous solutions, ointments, sticks, etc.) used to reduce and/or eliminate the unsightly skin effects of cellulite.

Cellulite^' is the most widespread and least tolerated defect in appearance in women. It is an aesthetic problem which is related to causes such as a sedentary lifestyle, predisposition, poor nutrition and hormone problems. It is mainly located, in order of importance, on the thighs, buttocks, abdomen/sides, knees, arms. By the term cellulite (oedemato-fibrosclerotic pannicolopathy) is meant a particular progressively degenerative change in subcutaneous adipose tissue. In most cases cellulite is also associated with local adiposity, from small accumulations of fat to pads of fat on the thighs, buttocks and stomach. This invention relates to a cosmetic preparation which is suitable for the treatment of unsightly skin caused by cellulite which is distinguished in that it specifically treats three different degrees of complexity of the problem at four different ages (20, 30, 40 and 50 years) . The 3 degrees of complexity in these defects are described by the inventors as "Orange Peel Skin, Orange Peel Skin with Local Adiposity, and Orange Peel Skin with Local Pads of Fat."

Specifically the invention relates to the association of Coenzyme A, extracted from Bupleurum chinensis and Horse Chestnut extract for the treatment of defects of the first degree of complexity defined as Orange Peel Skin. Lipases and Caffeine are added to this association of functional substances for the treatment of defects of the second degree described as Orange Peel Skin + Local Adiposity, and Lipases, Caffeine and Carnitine for the treatment of defects of the third degree defined as Orange Peel Skin + Local Pads of Fat.

As far as the age distinction is concerned, an increase in the concentration of the active ingredients which is characteristic for the degree in question corresponds to the increasing age ranges. In other words the concentration of the active ingredients is gauged in relation to the specific aesthetic requirement and age in order to obtain the best result. The inventors' decision to diversify the preparation by age ranges derives from the fact that the active ingredients act on the metabolism of triglyceride deposits to encourage mobilisation and combustion, and the finding that a slowing of metabolic functions in general and lipid functions in particular is normally associated with advancing age. There is therefore a progression of the problem over time and cellulite which appears before the age of 20 is physiologically different from the cellulite which appears after the age of 50. The preparations subdivided by age ranges must therefore have an increasing power to stimulate the mobilisation of reserve lipids with the increasing age of the woman treated, given that both the starting situation (metabolic activity and turnover of deposited triglycerides) and the ability to respond to an active ingredient vary according to the different ages considered.

It is known that skin defects due to cellulite are the macroscopic and visible consequences of a disturbance affecting the hypodermis, tissue which lies beneath the dermis, of a predominantly adipose nature, whose metabolic, lipolytic and liposynthetic activity is intense and important for regulation of the body's energy balance. The formation of cellulite starts with degeneration of the microcirculation in the adipose tissue and a consequent change in its important metabolic functions. The change in the adipose tissue is manifested as hypertrophy of the adipose cells, and changes in the permeability of the capillaries with a consequent leakage of plasma and the formation of oedema. The progress of this situation results in an increase in the number and thickness of the reticular fibres surrounding the adipose sites with a consequent reduction in exchanges, the accumulation of toxins, and loss of elasticity in the skin, which appears pallid and hypothermic. It leads to the formation of nodules, those small structures encapsulated in collagen fibres which further hinder the microcirculation and give the skin its characteristic orange peel appearance. Cellulite occurs more frequently, and its progress is more accelerated, in the presence of some hypertrophy of the adipose panniculus of the hypodermis, especially if localised in the lower limbs.

The inventors have tackled the problem of skin defects due to cellulite on the basis of their classification. In fact the complexity of the problem is such that it cannot be reduced to a single reference frame. Three different stages of complexity in the problem have therefore been identified:

- the first degree is described as Orange Peel Skin

- the second degree is described Orange Peel Skin with local adiposity

- the third degree is described as Orange Peel Skin with local pads of fat.

"Orange Peel Skin" is the externally visible consequence of a degenerative inflammatory process in the connective tissue, together with changes in the shape and volume of the adipose cells, together with other associated causes such as the insufficient drainage of fluids by the microcirculation. For this reason the inventors have identified an active ingredient containing Coenzyme A in association with a plant complex activating lipolysis, extract of Bupleurum falcatum and Horse Chestnut extract for treatment of the first degree of cellulite, described as "orange peel skin".

As is known, Coenzyme A is a carrier which binds fatty acids to the cellular cytoplasm and makes it possible for them to cross the mitochondrial membrane through an active transport system, and become included in their main metabolic pathway, beta-oxidation. By supplying additional quantities of Coenzyme A (obtained biotechnologically from a selected cell line cultured on specific substrates) to the preparation to which the invention relates, the transport of fatty acids into the mitochondria is assisted, together therefore with their removal from the adipocytes, with a consequent improvement in the appearance of the orange peel in terms of greater smoothness of the skin. The plant extract from Bupleurum falcatum stimulates lipolysis acting on another stage of the same, that is through increasing cyclic AMP (adenosine monophosphate) through the stimulation of G proteins. Cyclic AMP is a small molecule whose importance in the metabolic pathway of lipolysis has been known for a long time and is proven in the literature.

The effectiveness of the association between Coenzyme A and Bupleurum falcatum on reducing orange peel skin defects due to cellulite has been proven through an in vivo test on twenty volunteers in the course of which the condition of the skin was monitored by profilometry.

The test included twenty volunteers, who applied a cream containing the active ingredients described above to the outer part of the thighs twice per day for two months .

The condition of the skin was evaluated on the first, twenty eighth and fifty sixth day of the treatment. In order to render the skin deformation which had to be detected more obvious a bilateral compressive force was applied to the outer part of the thigh. The acquisition of data from the surface of the epidermis in the form of digital photographs was carried out in the presence of incident light in order to accentuate its irregularity. The photographs were analysed by software capable of describing the condition of the skin in terms of average roughness (parameter Ra) and mean deformation amplitude (parameter Rz) . The values of parameters Ra and Rz found in this way were analysed using Student's test with a significance level of 5%. The mean Ra and Rz values which resulted form the investigation are shown in the table below. day 0 day 28 day 56

The results obtained show a variation in the same direction in both parameters: both mean roughness and the amplitude of deformation decreased, indicating an improvement in the general condition of the skin in terms of increased smoothness and reduced orange peel effect. The second degree in the classification of defects due to cellulite made by the inventors is characterised by the formation of local adiposity which is added to the orange peel skin, making its appearance worse. For the treatment of this degree of cellulite the inventors decided to enrich the preparation containing the active ingredients already described for the first degree with another active ingredient comprising the enzyme Lipase (obtained by fermenting processes on an industrial scale) in association with Caffeine. ■ Both these molecules have an important role in the mobilisation of deposited triglycerides, and in their decomposition to glycerol and fatty acids, which can then enter the metabolic pathway through which they undergo combustion. The effectiveness of the active ingredient described above was demonstrated by an in vivo test performed on eleven volunteers over a total period of four weeks. The volunteers applied either a gel containing the active ingredient under test, or a gel without the active ingredient acting as a control, twice per day throughout the duration of the test. The thickness of the subcutaneous fat layer was measured on the first, fourteenth and twenty eighth day of the treatment, using images obtained by echography and ultrasound. The investigation demonstrated that the gel containing the active ingredient tested brought about an average reduction of 12.2% more in the thickness of the subcutaneous adipose tissue than the placebo after four weeks application.

The echographic measurements of the thickness of the subcutaneous adipose layer (in mm) are shown in the following table.

The third and most complex stage in the skin defects due to cellulite is characterised by a further aggravation of localised skin adiposity, in addition to orange peel skin, which takes the appearance of pads. The inventors found that this stage had to be treated with the addition of a further molecule capable of accelerating metabolism and combustion of lipids in order to reduce the most obvious skin defects due to cellulite such as localised adiposity and pads, to the preparation in addition to the three active ingredients described above (the association of Coenzyme A and Bupleurum falcatum, Horse Chestnut extract, and the association of Lipase and Caffeine) . This molecule is Carnitine. This works together with Coenzyme A in the active transport system necessary for passing fatty acids from the cytoplasm of the adipocytes to the mitochondria, the cellular location where their oxidation takes place. The presence of this molecule, which interacts with the other active ingredients present in a synergistic manner, makes it possible to amplify the accelerative effect on lipid metabolism. The effectiveness of the active ingredient was evaluated by means of an in vivo test which measured the thickness of the subcutaneous adipose layer by echography and ultrasound.

The investigation included 25 volunteers aged between 20 and 50 years. A cream containing the active ingredient under test was applied to the posterior part of a thigh and was caused to be absorbed by massaging. In parallel a placebo cream was applied to the other thigh, and the investigation was performed in a double blind manner.

The thickness of the lipid layer was measured on the first and last day of treatment, that is after 4 weeks application. The results of the investigation show that there was a reduction of 7.6% in the lipid layer in comparison with placebo in the thigh treated with the active ingredient. The decrease in the thickness of the hypodermis (in mm) determined by echographic measurements is shown in the following table.

In all the preparations described above for treatment of the three degrees of complexity and the four age ranges the inventors included glycol extract of Horse Chestnut in order to take advantage of its improving and stimulating properties on the function and nutrition of the microcirculation. The addition of Horse Chestnut extract was considered to be desirable, given that insufficient drainage of fluids due to poor microcirclation is one of the main contributory causes for occurrence of the problem in question.

The effectiveness of the preparation as a whole was evaluated by a self-assessment investigation involving 61 selected volunteers aged between 20 and 55. The investigation lasted two months, during which the volunteers applied the emulsion to both the thighs, twice per day. The results of the investigation at the end of treatment were as follows: - 65% of those interviewed reported an improvement in orange peel skin, - 60% of those interviewed noted an improvement in the defects due to cellulite, - 95% of those interviewed found that the skin was smoother at the end of the treatment, - the assessment of the effectiveness of the product by the volunteers was as follows: 8.3% of the volunteers felt that it was very good, 65% good, 15% sufficient, 10% insufficient, and 1.7% were unable to give an opinion,

- 80% of those interviewed would recommend the product to other women,

- 83% of those interviewed found that the product used was effective against the defects due to cellulite, the percentage rising to 94% if the women aged over 50 are considered.

The subject matter of this invention therefore comprises a preparation to reduce the skin defects due to cellulite as described in appended claim 1.

A more detailed description of the composition of a preferred embodiment of the preparation according to the invention will now be provided. According to this embodiment, which resulted in the favourable results illustrated above, the preferred composition of the preparation, in, as mentioned, any form and consistency, comprises:

- coenzyme A in a quantity of between 0.00002 and 0.35°-- of the weight of the preparation, - extract of Blupeurum falcatum in a quantity of between 0.014 and 2.45s-- of the weight of the preparation,

- Horse Chestnut extract in a quantity between 5 and

---5 U so _f - lipase in a quantity between 0.00002 and 0.035!Ό of the weight of the preparation,

- caffeine in an amount between 0.0001 and 2^D.Ό,

- carnitine in a quantity varying between 0.01 and 2Vo of the weight of the preparation. Other formulations with different proportions of the various components may however be produced as stated in the appended claims .

Claims

Preparation for topical use of any form and/or consistency for reducing and/or eliminating the skin defects due to cellulite, characterised in that its composition comprises: a) Coenzyme A, b) Bupleurum falcatum extract, c) Horse Chestnut extract.

2. Preparation according to claim 1, characterised in that its composition also comprises: Lipase and Caffeine.

3. Preparation according to claim 2, characterised in that its composition also comprises: Carnitine

4. Preparation according to claim 3 characterised in that in it: d) Coenzyme A is present in a quantity between 0.00002 and 0.35. of the weight of the preparation, e) the extract of Bupleurum falcatum is present in a quantity between 0.014 and 2.45°--. of the weight of the preparation, f) the Horse Chestnut extract is present in a quantity between 5 and 30s-, g) lipase is present in a quantity between 0.00002 and 0.035s- of the weight of the preparation, h) caffeine is present in a quantity between 0.0001 and 2-, i) carnitine is present in a quantity between 0.01 and 2°s- of the weight of the preparation.