WO2003017966A2

WO2003017966A2 - Use of luffa cylindrica oil in cosmetic and dermopharmaceutical compositions

Info

Publication number: WO2003017966A2
Application number: PCT/FR2002/002933
Authority: WO
Inventors: Karl Lintner
Original assignee: Sederma
Priority date: 2001-08-27
Filing date: 2002-08-27
Publication date: 2003-03-06
Also published as: WO2003017966A3; FR2828811A1; FR2828811B1; AU2002356096A1

Abstract

The invention concerns the use of Luffa cylindrica oil, on its own or in combination with other active ingredients, in cosmetic or dermopharmaceutical compositions for all types of care for the skin, mucosa and skin appendages (nails, hairs and hair), especially for restoring lipids to any biological tissue which has lost same, for whatever reason, thereby enabling it to fulfill its role properly as protective barrier against daily external attacks.

Description

TITLE Use of Luffa cylindrica oil in cosmetic and dermopharmaceutical compositions.

The skin is an organ, the main physiological function of which is to act as a barrier against the external aggressions that the body undergoes daily. For this, its biochemical composition, and more particularly that of the stratum corneum, is of capital importance. Any imbalance, qualitative or quantitative, results in multiple dysfunctions which lead at best to simple discomfort, at worst, to more or less pathological situations. The very particular morphology of the stratum corneum, the interweaving of corneocytes and lipid lamellar structures, often shown schematically by the image of an assembly of bricks and mortar, is essential for the maintenance of this barrier function of the skin. Until now, we have represented the entangled corneocyte envelopes in an intercellular matrix composed essentially of ceramides, cholesterol and fatty acids.

The progressing analysis techniques and the recent work of several teams on in vivo samples have made it possible to give a more complete and finer picture of the constitution of the epidemic. The detailed exploration of the lipid composition of the different layers of the epidermis was approached by LANRIJSEN (1994, Arch. Dermatol., 286: 495). He observed during sequential scraping, layer after layer (technique also known under the Anglo-Saxon name: strippi g), a large amount of fatty acids, di- and triglycerides, cholesteryl esters in the outermost layers gradually leaving a greater emphasis on ceramides, cholesterol and phospholipids with remarkable stability in the composition of subtypes of ceramides from one layer to another.

The following table indicates the percentage of the different lipid fractions found in the skin samples obtained after 1 to 6 sequential scrapings. 1 2 3 4 5 6

Glucosphingolipids 3 3 3 4 6 5

Ceramides 15 20 21 23 22 21

Free cholesterol 7 7 8 11 17 11 Free fatty acids 30 11 13 11 13 14

Di / Triglycerides 27 32 26 24 24 23

Cholesterol esters 11 15 15 14 13 13

Squalene 4 4 5 5 5 4

Alkanes 1 4 4 3 3 4 Phospholipids 0 0 0 0 0 10

Cholesterol sulfate 0 0 3 3 0 0

He also highlighted the very great interindividual variability affecting the relative proportions between the different lipids and the ceramides, and objectified the importance of these different lipid layers on the maintenance of the insensible water loss (PIE, also known under the name Anglo-Saxon: TEWL or transepidermal water loss). ï 2 3 4 5 6 TËwi ^"" (gm ^: ïrι ^{: ï} ) 6 ^" il ^" 27 38 45 85

Then came the work of KINDNESS (1997, Arch Dermatol, 289. 78) which indicated a significant change in the relative composition of lipids beyond the ^3rd layer stripping. Free fatty acids, while regularly decreasing from layer 1 to 5, see their composition pass from a majority of short chain lipids mono or polyunsaturated in Cl 4: 0 to C 18: 3 to lipids with long chains in C24 : 0 generally saturated. The following table shows the results obtained during the gas chromatographic determination of the free fatty acids (chain length and degree of unsaturation) expressed in μg / lOOμg (ND: not detected) for scraping levels 1 and 5.

| C14: 0 C14: l C16: 0 C16: l C18: 0 C18: l C18: 2 C20: 0 to Total C24: 0

1 C22: l C14-C18

1 | 0.6 0.3 2.1 0.8 1.1 1.6 0.2 ND 6.7 0.5

5 | 0.2 0.4 1.6 0.4 0.7 0.9 0.2 ND 4.4 0.9 This observation of the existence of larger quantities of fatty acids with a shorter chain at the surface explains the greater fluidity of the lipids of the upper layers which, becoming less cohesive with one another, prepare and promote flaking on the surface. Beyond this mechanical and protective role, these surface fatty acids play an important role in maintaining the skin barrier and their deficit leads to insufficient fatty acid / cholesterol (and / or ceramides) ratios which characterize ichthyotic patients whose TEWL is high (1994, Lavrijsen et al., Arch. Dermatol 286: p495) Finally, with the most recent work by NORLEN (1999, Arch DermatoL290: 508; 1999, J Invest Dermatol, 112: 72), the the most faithful possible image of the lipid composition could be established with the highlighting of the very particular composition, in fatty acids, of the innermost layers of the stratum corneum. A study carried out on 22 subjects shows the presence of lipids at a rate of 0.15 mg / cm ² of skin with saturated fatty acids with long and very long chains of C20 to C30.

The highest proportion is lignoceric acid at C24: 0 (40%), followed by the lipids C26: 0, C25: 0 and C22: 0 which together total 45% and are secondarily the most strongly represented.

According to the author, this particular composition of the internal stratum corneum probably contributes to a transition from the crystalline multilamellar state to an "amorphous" state, reinforcing greater impermeability with respect to water loss. The lipid composition of the human skin barrier is summarized in the following table

Cholesteryl Fatty acids Cholesterol Ceramides free esters

% Weight 18 11 24 47

% Molar 15 - 16 32 37 Apart from free fatty acids, the esterified fatty acids entering the cholesteryl esters are essentially monounsaturated and made up of 70% oleic acid (Cl 8: 1), while those coupled in the form of acyl ceramides are essentially linoleics ( Cl 8: 2). We already know the importance of ceramides in maintaining hydration, recently supported by SHINISHI (2000), which demonstrates (in animals) a very strong increase in PIE, during administration a diet deficient in essential fatty acids, preventing the incorporation of linoleic residues in ceramides 1 and resulting in a strong disturbance of the EIP. In summary to the numerous information from these recent works (1996-1999) it appears that the free surface fatty acids are essentially short chain fatty acids, often monounsaturated and lower than C: 20, while the fatty acids of the layers deep are long chain, from C: 24 to C: 30, and are completely saturated. Mono and polyunsaturated C: 18 linked fatty acids are closely associated with the genesis of cholesteryl esters and ceramide 1.

These lipids form multilamellar layers localized in the intercellular spaces: it is this spatial organization which is essential for maintaining the barrier function of the epidermis and preventing water loss, but it also determines the mechanical properties of the skin, a very coherent structure in depth, more inhomogeneous on the surface and ensuring its capacity of desquamation. Any damage to the skin surface, essentially through improper use of toiletries, disrupts this natural arrangement and leads, via the imbalance between free surface fatty acids and deep fatty acids, to an alteration of the barrier effect with an increase in the insensible water loss.

The cosmetic industry is therefore fully in its role when it is constantly looking for new concepts and products capable of preventing or reducing skin dryness of all origins. The object of this patent application lies in the discovery, and in the demonstration, that a new solution can be proposed to rebalance effectively a skin which has lost, for whatever reason, its initial composition and thus, restore its optimal effectiveness as a barrier against the various external aggressions suffered daily.

A lipid-replenishing cosmetic active ingredient must provide the skin with the right proportion of different fatty acids allowing it to reconstitute its lipids in the surface areas: it is in this context that we have selected vegetable sponge oil or Luffa cylindrica oil, because its composition is optimum compared to the desired effect. Luffa cylindrica, also called "wild silk gourd" in China, "loofah" or "vegetable sponge" in France, belongs to the Cucurbitaceae family.

It is a creeping and climbing vine which after flowering gives fruit to the highly developed fibrous vascular system. After drying this internal network, there remains a fibrous bread, widely used throughout Asia as a sponge or towel. This plant produces a squash that can only be eaten in its immature form.

After a bright yellow flowering, this cucurbit gives a fruit which can reach a large size (1 to 3 kg) which produces many black seeds, oblong and of good size (1cm in length) from which glycoproteins with antiviral properties (protein ribosome inactivator [RU AN, 1998] and anti-tumor [POMA, 1999].

A clinical study (1999) also reports an anti-hay fever activity of a loofah extract in spray form. From the culture of Luffa cells, certain teams have isolated bryonolic acid whose activity of suppressing delayed hypersensitivity seems very interesting [TANAKA, 1991]. The invention which is the subject of this patent application resides in the fact that we have discovered that the oil obtained from the seeds of Luffa cylindrica applied regularly topically makes it possible to maintain the cutaneous lipid constitution at a qualitative and quantitative level. optimum to allow it to optimally play its role of barrier between the body and the outside mileiu. Obtained by cold pressing, or by any other method, from seeds of Luffa cylindrica, this oil is characterized by a very important composition in polyunsaturated fatty acids (PUF A) with short chains, greater than 60%. Throughout the development of the invention which is the subject of this patent application, this analytical characteristic was found during the analyzes carried out on this product.

We have previously seen the importance of these fatty acids in terms of the constituents of the epidermis, a deficit of which leads to the following disorders:

> Flaking disorders> Hypertrophy of the sebaceous glands and hyperkeratosis

> Weakened skin capillaries

> Increased insensible water loss

Of oleic-linoleic type, Luffa cylindrica oil contains a total of 79% short chain fatty acids, including 62% essential fatty acids in linoleic (60%) and γ-linolenic form (1.5 to 2%).

The following table allows a more detailed examination of the sub-distribution of fatty acids which enter into the total composition of Luffa cylindrica oil (Luffa), which brings other sources of interest for this oil compared to that stratum corneum (1997, Kindness; ND: not detected). C14: 0 C14: l C16: 0 C16: l C18: 0 C18: l C18: 2 C20: 0 to

C22: l

Stratum corneum 4.0 8.0 30.0 8.0 13.0 17.0 4.0 ND

Luffa 0.1 ND 12.2 0.1 5.5 19.6 59.7 Traces

Indeed, there is a distribution of short-chain monounsaturated to polyunsaturated fatty acids between C14: 0 and C18: 2: situation very similar to that of the skin. Palmitic acid (C16: 0), 30% of the lipids of the stratum corneum is also well represented with 12% in the oil of Luffa cylindrica.

Oleic acid (C18: l) represents 17% of skin fatty acids and 19.6% of fatty acids in Luffa cylindrica oil. The peculiarity of Luffa cylindrica oil is its high content of linoleic acid Cl 8: 2 (59%), essential fatty acid constituting ceramide 1, one of the pivots in the periodic lamellar structural organization and deficient in dry skin or elderly (2000, Schreiner). Thus, with the Upidic composition of Luffa cylindrica oil, close to that of the stratum corneum, it is possible to obtain a noticeable beneficial effect on damaged, defatted skin and having an altered PIE.

The following two examples will illustrate cosmetic preparations effective for lipid replenishing the skin tissue made with Luffa cylindrica seed oil. Example n ° 1: Washing base

0.10 potassium sorbate

Empicol ESB3 / M 30.0

Incronam 30 4.0

Empilan LIS 1.5

Liquid Crothix 2.0

Phenova 0.8

Luffa Cylindrica Oil 2.0

Perfume & Demineralized water qs 100

Example 2: Gel after shower

NaOH IO N 0.10

Pemulen TR-2 0.30

Luffa Cylindrica Oil 3.0

Perfume & Demineralized water qs 100

The following two examples demonstrate the effectiveness of our invention by in vivo tests. Example No. 3: Skin Lipid Removal

It is possible, using new infrared techniques (known as ATR-FTIR), to pinpoint the lipid signals of the stratum corneum (inter-corneocytic lipids). The absorption by the epidermis of an infrared emission results in the re-emission of different return signals between proteins, water and lipids because they are specific to the typical bonds of each molecular category (OH bond for water; amide bond for proteins; CH2 bonds, CH = CH, C = O esters for lipids). On a standard normal skin profile, it is thus possible to identify 4 signals specific to the following lipid patterns:

> A double peak 2851/2919 cm-1 (C-H2)

> Unρic at l740 cm-l (C = O)

> Unpic at l450 cm-1 (-C-H)> The probe, made up of a Zn-Se crystal, is simply applied on contact with the skin, the re-emitted signals are directly recorded on the device. We expect, for a defatted skin, an alteration of this profile on these 4 specific peaks of the constituent lipids. During the following test we first established a comparison of the typical profiles for the normal state and the defatted state.

We then selected a panel of 10 volunteers: the skin of the forearm was chosen as the test area.

Half of the panel, ie 5 volunteers, presented defatted skin, the second half of the panel normal skin which was subjected to defatting by a simple toilet with a cleansing base (example no. 1 without Luffa): the initial state of the spectrum

"defatted" was recorded for all the subjects, then a gel containing 2% of Luffa cylindrava oil was then applied (cf. example n ° 2).

In order not to take into account the transient surface lipid state (effect of spreading the product), the final measurements were taken after 1 hour. The following tables (n ° = number of the volunteer whose values are given, ® = mean, Δ = observed variation, p = statistical significance, Luffa = Oil of

Luffa cylindrica at 2% of example n ° 2) indicate the results obtained by taking into account the 4 peaks of lipids.

A / Subjects with skin deficient in lipids

Signals 2851/2919 cm ^'1 Signal 1740 cm ^-1 Signal 1450 cm ^"1

(area below peak) (area below peak) (area below peak) n ° Luffa initial state Luffa initial state Luffa initial state

1 0.78 2.60 0.015 0.046 0.107 0.150

2 1.35 1.55 0.073 0.12 0.217 0.240

3 0.20 0.43 0.016 0.03 0.038 0.044

4 0.28 0.89 0.015 0.091 0.030 0.080

5 0.65 1.84 0.035 0.126 0.122 0.100

® 0.65 1.46 0.031 0.083 0.103 0.143

Δ x 2.2 X 2.6 X 1.4 p p = 0.05 p = 0.02 p = 0.03

Value of lipid enrichment signals in volunteers with initial skin deficient in lipids then after application of 2% of Luffa cylindrica oil Volunteers whose skin was naturally defatted saw their infrared profile change significantly by a factor of improvement of approximately 1.4 to 2.6, highly significant for each signal peak, indicating a perfect incorporation of the fatty acids from the sponge oil within the corneal structure. B / Subjects with normal skin defatted by the use of a cleaning product

Signals 2851/2919 cm ^"1 Signal 1740 cm -1 Signal 1450 cm ^{" 1}

1 1.02 0.72 2.47 0.063 0.051 0.190 0.179 0.092 0.360

2 0.76 0.30 0.59 0.062 0.013 0.045 0.112 0.063 0.112

3 1.20 0.40 1.16 0.059 0.051 0.128 0.149 0.057 0.196

4 8.83 2.44 5.42 0.801 0.180 0.501 0.0856 0.306 0.560

5 2.33 0.68 2.00 0.067 0.028 0.112 0.304 0.081 0.244

® 2.82 0.90 2.32 0.210 0.065 0.195 0.320 0.111 0.294

Δ Deficit Return Deficit Return Deficit Return x3 to x3 to x3 to normal normal normal pp = 0.07 p = 0.50 p = 0.07 p = 0.80 p = 0.05 p = 0.07 Value of lipid signals in volunteers with normal initial skin made deficient by cleaning with a cleansing base followed of an application of a gel containing 2% of Luffa cylindrica oil.

Volunteers whose skin was normal, which was dissipated by the device of a washing base, saw their signals collapse by a factor of 3; 1 hour after applying the gel containing 2% of Luffa cylindrica oil, a return to normal was obtained with initial and final values not statistically different. Example 4: Insensible water loss

The daily shower with a washing agent gradually alters the skin barrier, leads to the defatting of the upper layers of the epidermis and therefore its corollary: increase in PIE. The insensible water loss is measured with a Tewameter (TM210, Courage and Khazaka) using a probe simultaneously capturing the relative humidity, the temperature and the PIE expressed in g / h / m ^D.

In a preliminary trial carried out on 4 volunteers, the measurement of the EIP after 4 days of using a washing base (example n ° 1 but without the oil of Luffa cylindrica) showed a net increase of this on 2 sites previously chosen on each of the legs. The following table shows the results observed 2 hours after using the washing base.

Site the Site 2 T0 T0 T4jours T4jours P ^'medium lift ^e 8.0 ^"" 8.6 ^"7 ^~ 8 8.8% increase PIE - +7.6 - +13.2

The increase in PIE at the 2 sites (+ 7.6% and + 13.2%) clearly demonstrates the weakening effect of the skin barrier by the repeated use of a conventional washing base.

Similarly, a total panel of 10 volunteers applied to the 2 sites and for 8 days, either the same washing base (example no.1 but without Luffa cylindrica oil) on site no.1, or this base washing (example n ° l, so with oil 2% Luffa cylindrica oil) on site 2, the PIEs were recorded in OJ and J8, the following results were obtained:

Site l S ite 2

TO * T8 days T0 T8 days

Volunteer # 1 9.3 11.0 9.2 9.7

Volunteer # 2 9.2 8.5 10.2 8.8

Volunteer # 3 9.1 11.0 8.9 9.2

Volunteer n ° 4 7.0 7.7 6.8 6.5 Volunteer n ° 5. 6.8 7.7 7.7 7.7

Volunteer n ° 6 6.3 8.7 8.5 5.9

Volunteer # 7 9.3 6.8 8.4 6.2

Volunteer # 8 8.8 6.4 8.1 6.3

Volunteer # 9 10.2 9.1 9.4 8.0 Volunteer # 10 10.0 8.9 9.6 8.0

Average PDE 8.6 8.0 8.7 7.6

% Variation _ -0.2% _ -12%

In this test, the PIE is measured 8 hours after using the shower gel, so the measurement reflects the long-term consequences of the effects of the morning shower. In a natural way, a skin delipidated by aggression in the morning, will reconstitute its lipid level during the day: we see that for the control panel, 5 of the volunteers still have a lipid deficit at the end of the day (vol n ° l, 3 , 4, 5, 6) with an increased PIE.

On the other hand, the results obtained with the washing base containing 2% of Luffa cylindrica oil show a protective effect, with for all the subjects, a reduction in the PIE, and a very significant improvement in the barrier effect, in 12% average after 8 days of use.

The use of a simple washing base, gradually changes the skin barrier with an increase in PIE. The use of a washing base containing Luffa cylinbrica oil helps maintain the skin's protective capital and restores a PIE beforehand altered, with an improvement of 12%.

In conclusion, the Luffa cylindrica oil, by its fatty acid composition close to that of the epidermis, makes it possible to lipid a skin initially deficient in lipids. Due to the activity demonstrated above, Luffa cylindrica oil can be used as it is or in cosmetic or dermopharmaceutical preparations for all skin care, mucous membranes and dander (nails, hair and hair), especially to relipidize any previously defatted biological tissue, for whatever reason, thus enabling it to correctly fulfill its role as a protective barrier against daily external aggressions.

In addition, its obtaining, its ease of incorporation into all preparations conventionally used in cosmetics or dermopharmacy as well as its cost price, makes it an elegant solution and perfectly usable at the industrial level to solve the skin problems exposed above.

In the cosmetic or dermopharmaceutical composition, it may be advantageous to combine Luffa cylindrica oil with other active agents in order to reinforce its effect by additivity or synergy between the effects of these different products, or in order to associate the effect described in this patent application with another beneficial physiological effect on the skin, mucous membranes, dander (nails, hair and hair).

In the finished cosmetic or dermopharmaceutical composition, the Luffa cylindrica oil can vary between 0.001% and 50% (w / w), preferably between 0.1% and 10% (w / w). Luffa cylindrica oil, alone or in combination with other active ingredients, is used in any dosage form used in cosmetics or dermopharmacy: HE and W / O emulsions, milks, lotions, ointments, hair lotions, shampoos, soaps, sticks and pencils, sprays, body oils, without this list being exhaustive. Luffa cylindrica oil is used in the form of a solution, dispersion, emulsion, or encapsulated in vectors such as macro-, micro- or nanocapsules, liposomes or chylomicrons, or included in macro-, micro- or nanoparticles, or in micro-sponges, or adsorbed on powdery organic polymers, talcs, bentonites and other mineral supports. Luffa cylindrica oil, alone or in combination with other active ingredients, is incorporated into any other ingredient usually used: extraction and / or synthetic lipids, gelling and viscosifying polymers, surfactants and emulsifiers, hydro- or active ingredients hposolubles, plant extracts, tissue extracts, marine extracts, sun filters, antioxidants.

Luffa cylindrica oil, alone or in combination with other active ingredients, is used in cosmetic or dermopharmaceutical compositions; used for all care of the skin, mucous membranes and integuments (nails, hair and hair), especially to lipid any biological tissue previously defatted, for any reason whatsoever, thus enabling it to correctly fulfill its role of protective barrier against daily aggression outside. Luffa cylindrica oil, alone or in combination with other active ingredients, is incorporated into cosmetic or dermopharmaceutical compositions for the preparation of a medicament used for all care of the skin, mucous membranes and integuments (nails, hairs and hair), especially to lipid any biological tissue previously defatted, for whatever reason, allowing it to correctly fulfill its role as a protective barrier against daily external aggression. Luffa cylindrica oil, alone or in combination with other active ingredients, is incorporated into cosmetic or dermopharmaceutical compositions, linked or incorporated or absorbed or adsorbed in the form of macro-, micro- and nanoparticles or in macro-, micro - and nanocapsules, in textiles, synthetic or natural fibers, wool and any material that can be used to make clothes and underwear for day or night, directly in contact with the skin or hair to allow a continuous topical delivery.

Claims

1. Use of Luffa cylindrica oil in cosmetic and dermopharmaceutical compositions for all care of the skin, mucous membranes and integuments (nails, hair and hair), especially to lipid any biological tissue previously defatted, for whatever reason either, thus enabling it to properly fulfill its role as a protective barrier.

2. Cosmetic and dermopharmaceutical compositions for all care of all skin care, mucous membranes and dander (nails, hair and hair), especially for lipidizing any previously defatted biological tissue, for whatever reason, thereby enabling it to correctly fulfill its role of protective barrier, characterized in that they contain Luffa cylindrica oil obtained by cold pressing or by any other method from Luffa cylindrica seeds, and that the concentration of this oil in fatty acids polyunsaturated (PUF A) short chains is greater than 60%.

3. Cosmetic and dermopharmaceutical compositions according to claim 2, characterized in that the oil content of Luffa cylindrica can vary between 0.001% and 50% (w / w), preferably between 0.1% and 10% (w / w) .

4. Cosmetic and dermopharmaceutical compositions according to any one of claims 2 to 3, characterized in that they are in any galenical form used in cosmetics or dermopharmacy: O / W and W / O emulsions, milks, lotions, ointments, lotions capillaries, shampoos, soaps, sticks and pencils, sprays, body oils.

5. Cosmetic and dermopharmaceutical compositions according to any one of claims 2 to 4, characterized in that the oil of Luffa cylindrica is incorporated in cosmetic vectors such as liposomes, chylomicrons, macro-, micro- and nanoparticles as well as macro-, micro- and nanocapsules, to absorb them on powdery organic polymers, talcs, bentonites and other mineral supports.

6. Cosmetic and dermopharmaceutical compositions according to any one of claims 2 to 5, characterized in that the oil of Luffa cylindrica is used with any other ingredient usually used in cosmetics: extraction and / or synthetic lipids, gelling and viscous polymers, surfactants and emulsifiers, water- or liposoluble active principles, in particular caffeine, extracts from other plants, tissue extracts, marine extracts.

7. Use of the compositions according to any one of claims 2 to 6 for the preparation of medicaments for all care of the skin, mucous membranes and integuments (nails, hair and hair), especially for lipidizing any previously defatted biological tissue, for whatever reason, allowing it to properly fulfill its role as a 4th protective barrier.

8. Use of the compositions according to any one of claims 2 to 6, characterized in that the oil of Luffa cylindrica is bound or incorporated or absorbed or adsorbed in the form of macro-, micro- and nanoparticles or in macro-, micro - and nanocapsules, in textiles, synthetic or natural fibers, wools and any material that can be used to make clothes - and underwear, day or night, directly in contact with the skin or hair to allow it continuous topical delivery.