STERILE LIQUID COMPOSITION FOR FILLING WRINKLES

Abstract

The subject matter of the present invention is a sterile liquid composition dedicated to administration into or through the skin and/or the lips, wherein said composition comprises, in a physiologically acceptable medium, at least one photo-crosslinkable compound, wherein said compound comprises at least one activated photo-dimerizable group having at least one activated double bond and selected from photo-dimerizable groups carrying a stilbazolium function of formula (Ia) or (Ib) and wherein the photo-dimerizable groups carry a styrylazolium function of formula (II), the photo-dimerizable group(s) being carried by a partially or totally hydrolysed poly(vinyl acetate) polymer, a polysaccharide or a polyvinyl alcohol

Claims

1. A sterile liquid composition dedicated to administration into or through the skin and/or the lips, said composition comprising, in a physiologically acceptable medium, at least one photo-crosslinkable compound, wherein said compound comprises at least one activated photo-dimerizable group having at least one activated double bond and selected from: a) photo-dimerizable groups bearing a stilbazolium function of formula (Ia) or (Ib): ##STR00021## where: R represents a hydrogen atom or a C.sub.1-C.sub.4 alkyl or C.sub.1-C.sub.4 hydroxyalkyl group, R represents a hydrogen atom or a C.sub.1-C.sub.4 alkyl group, and X.sup. denotes an ion selected from chloride, bromide, iodide, perchlorate, tetrafluoroborate, methyl sulfate, phosphate, sulfate, methanesulfonate and p-toluenesulfonate ions, ##STR00022## where: R denotes a divalent alkylene radical having from 2 to 8 carbon atoms, R represents a hydrogen atom or a C.sub.1-C.sub.4 alkyl group, and X.sup. has the same meaning as that described for formula (Ia) above, b) photo-dimerizable groups bearing a styrylazolium function of formula (II): ##STR00023## wherein: R.sub.1 denotes a hydrogen atom or a C.sub.1-C.sub.4 alkyl or C.sub.1-C.sub.4 hydroxyalkyl group, A denotes a sulfur atom, an oxygen atom or a group NR or C(R).sub.2, R, R representing a hydrogen atom or a C.sub.1-C.sub.4 alkyl group, and X.sup. has the same meaning as that described for formula (Ia) above, the photo-dimerizable group(s) being borne by a partially or totally hydrolyzed poly(vinyl acetate) polymer, a polysaccharide or a polyvinyl alcohol.

2. The composition as claimed in claim 1, characterized in that the photo-dimerizable group is a photo-dimerizable group bearing a stilbazolium function of formula (Ia): ##STR00024## where: R represents a hydrogen atom or a C.sub.1-C.sub.4 alkyl or C.sub.1-C.sub.4 hydroxyalkyl group, R represents a hydrogen atom or a C.sub.1-C.sub.4 alkyl group, and X.sup. denotes an ion selected from chloride, bromide, iodide, perchlorate, tetrafluoroborate, methyl sulfate, phosphate, sulfate, methanesulfonate and p-toluenesulfonate ions.

3. The composition as claimed in claim 1, characterized in that it is devoid of photoinitiator and/or of chemical initiator.

4. The composition as claimed in claim 1, wherein the photo-dimerizable groups are borne by a polyvinyl alcohol.

5. The composition as claimed in claim 1, wherein the photo-crosslinkable compound is a polyvinyl alcohol partly functionalized with one or more hydroxyl function(s) and one or more function(s) of formula (III): ##STR00025##

6. The composition as claimed in claim 1, characterized in that the degree of functionalization with photo-dimerizable units is at least 0.1%, or even at least 0.5%, or even at least 2%.

7. The composition as claimed in claim 1, wherein the photo-crosslinkable compound represents at least 2%, or even at least 5%, or even 10% of the total volume of the composition.

8. The composition as claimed in claim 1, also comprising at least one optical tracer or one fluorescent compound.

9. The composition as claimed in claim 1, also comprising at least one additional active agent, in particular an antiwrinkle active agent.

10. A cosmetic process for treating the skin and/or the lips, comprising the following steps: i. administration into or through the skin and/or the lips of a composition as claimed in claim 1, and ii. illumination of the skin and/or the lips treated according to step i. in order to crosslink the composition.

11. The cosmetic process for treating the skin and/or the lips as claimed in claim 10, wherein the illumination is a light source with radiation in the visible range and/or radiation in the UV range and preferably radiation in the visible range.

12. A system for treating the skin and/or the lips, comprising: a packaging containing at least one dose of a composition as claimed in claim 1, and a device for injection into or through the skin and/or the lips or a device for microperforation of the skin and/or of the lips, dedicated to the administration of said dose.

13. The treatment system as claimed in claim 12, also comprising an imager.

14. The treatment system as claimed in claim 12, also comprising an injection device suitable for intraepidermal and/or intradermal and/or subcutaneous injection.

15. The treatment system as claimed in claim 12, wherein the injection device is selected from a syringe, a set of microsyringes, a hydraulic laser device or a scalpel.

16. The treatment system as claimed in claim 12, wherein the injection device is suitable for the mesotherapy technique.

17. An assembly for treating esthetic imperfections of the skin and/or of the lips, comprising: i. a treatment system as claimed in claim 12, and ii. a lighting system capable of photo-crosslinking the compound.

18. The treatment assembly as claimed in claim 17, also comprising at least: i. one system for analyzing at least one area to be treated, ii. one source of other means of activation selected from a source of heat, of microwaves, of sound waves, a light source which does not facilitate crosslinking of the compound(s), iii. one system for applying a stress before or during the illumination, iv. one device for eliminating the unreacted compounds.

Description

[0336] The invention may be better understood from reading the following detailed description of nonlimiting implementation examples thereof and from examining the appended drawing, in which:

[0337] FIGS. 1A and 1B represent diagrammatically two methods of using a treatment system according to the invention,

[0338] FIGS. 2A to 2C represent injection devices of a treatment system according to the invention,

[0339] FIG. 3 represents diagrammatically a treatment assembly, and

[0340] FIGS. 4a and 4b represent a modeling system.

[0341] The preparation step shown in FIGS. 1A and 1B corresponds to preparing, on the one hand, the material for the injection, which depends on the technique selected, and, on the other hand, the composition to be injected.

[0342] The composition may be prepared in situ, or may be prepackaged, in particular in sterile packaging.

[0343] The packaging is suitable for the storage of at least one dose of the composition, where appropriate for the mixture thereof with a physiologically acceptable liquid medium, in a sterile environment.

[0344] The packaging may be arranged so as to allow, moreover, the sampling of said composition in the form of a solution or dispersion

[0345] Thus, according to a first embodiment, said packaging is scored so as to allow said composition to be sampled.

[0346] For example, it may be in the form of a single-dose capsule or vial, which has a scored end.

[0347] According to a second embodiment, said packaging has a seal which allows hermetic closing during storage and which can be pierced by a needle at the time of use.

[0348] According to one embodiment variant, said composition is formulated in the form of a dispersion or of a solution within the packaging.

[0349] According to another variant, said composition is present in powder form.

[0350] In such a variant, said packaging is suitable for the introduction of a sterile, fluid, physiologically acceptable medium in order to obtain a solution and/or dispersion of said composition under sterile conditions.

[0351] Such packaging may also be two-compartment packaging, one of the compartment s being dedicated to the storage of said composition in the powder form and the other to the storage of the physiologically acceptable liquid medium which must be combined therewith. These two compartments are advantageously separated by a blocking means configured so as to be moved and to then allow the content of the two compartments to mix.

[0352] Such a device is advantageously disposable.

[0353] FIG. 2A represents several syringes 20, prefilled with a dose of composition. The doses correspond, for example, respectively to 1 ml, 1 ml, 1 ml and 1 ml of composition.

[0354] In the variant of FIG. 2B, the syringe 20 is not prefilled and the composition is packaged in a sterile bottle 30. In the example shown, the bottle is hermetically closed with a closing member 35 made of a flexible material, able to be pierced by the needle of the syringe 20. Other modes of closure can be envisioned.

[0355] FIG. 2C represents a perspective view of a gun 25 used for an administration of the composition by mesotherapy. The syringe 20 and the sight 22 are preferably disposable.

[0356] The examples represented are not limiting. Those skilled in the art can select any known intradermal injection or application technique.

[0357] After administration of the composition, the area to be treated, for example the face as shown in FIG. 3, is lit so as to crosslink the compound.

[0358] In the example shown, the crosslinking is produced by an artificial light source;

[0359] in another variant, the crosslinking can be carried out in daylight.

[0360] The treatment system of FIG. 3 optionally comprises an electronic imager 4 produced according to DLP technology, using a DMD chip referenced 111. The latter can be attached to a platform 112 which can comprise, moreover, a processor 113 for controlling the chip, and also, optionally, a memory 114. In the example shown, the chip is represented on the same platform as the processor 113 and the memory 114, but said processor and said memory can be arranged differently.

[0361] The imager 4 represented in FIG. 3 receives light from a source 2 which may be a source that can emit both in the UV range and/or in the visible range or a source that can emit selectively in the visible range or in the UV range.

[0362] The source 2 may be a halogen lamp which emits in the UV and visible spectra, a discharge lamp or one or more LEDs capable of emitting, for example, in the UV range or in white light or light in a given color.

[0363] The imager 4 may comprise, as shown, optics 118, 119 and 120 respectively for condensing the light, focusing it on the DMD chip and ensuring focusing on the area to be treated.

[0364] When the source 2 has an emission spectrum both in the UV range and in the visible range, the imager 4 may comprise, as shown, a filter wheel 130, which intercepts the light beam, for example, between the condensing optic 118 and the focusing optic 119. Depending on the position of the filter wheel 130, the chip receives UV light or visible light, which is then directed to the optical outlet. It is thus possible to form, on the area to be treated, an image selectively in visible light and/or in the UV range.

[0365] In one variant which is not represented, the irradiator uses several DMD chips attached to a prism.

[0366] The arrangement shown in FIG. 3 can be used with the DMD chips replaced with LCOS chips.

[0367] Once the composition has been injected, the method shown in FIG. 1B also comprises a modeling step intended to force the material to give the skin a better conformation.

[0368] This step can be carried out by several means, optionally combined, in particular by suction, smoothing, extension, energy actions such as radiation by microwave or laser.

[0369] The modeling can be carried out in dim light, or even in the dark, before the beginning of the crosslinking phase.

[0370] In another variant, the modeling can be carried out simultaneously with the crosslinking, at least partly, for example can begin prior to and continue during the crosslinking step.

[0371] In one variant, the modeling is carried out by massaging the treatment area in order to preform the composition before crosslinking. The massaging can be done manually and/or using a massaging member.

[0372] FIGS. 4A and 4B show a system 40 for applying a stress, placed directly on the skin at the level of a wrinkle or of a furrow, as shown in FIG. 4A. The system generates forces which have the effect of retightening the skin.

[0373] The process shown in FIG. 1B also optionally comprises a step of eliminating the part of the composition which has not crosslinked.

[0374] Other features and advantages of the invention will emerge from the examples that follow, which are given as nonlimiting illustrations.

[0375] In the text hereinbelow, the proportions are given as weight percentages, unless otherwise indicated.

[0376] The expression comprising a is synonymous with comprising at least one, and between should be understood to mean limits inclusive.

[0377] The examples that follow are given as nonlimiting illustrations of the present invention.

[0378] The invention is not limited to the devices shown.

EXAMPLE 1

Synthesis of Xanthan Gum Grafted with Stilbazolium Groups

[0379] Deacetylated xanthan gum is prepared by dissolving 0.2% by weight of xanthan gum (Rhodicare XC from Rhodia) in water and by adding 0.025 mol of potassium hydroxide and 0.1% by weight of potassium chloride for 2 h 30 at ambient temperature, under a nitrogen atmosphere.

[0380] The alkaline solution is then neutralized with 0.05 mol of hydrochloric acid in order to adjust the pH to 6.5.

[0381] The solution is then dialyzed with distilled water using dialysis tubing (Snakeskin Pleated Dialysis Tubing, Pierce, Rockford, Ill., U.S.A.), and the deacetylated xanthan is recovered by lyophilization.

[0382] The deacetylated xanthan gum is redissolved in 20 ml of water. 0.2 g of concentrated phosphoric acid and 0.1 g of chloride compound (1) of formula:

##STR00019##

are dissolved in 1 ml of water and are added thereto.

[0383] The mixture is kept stirring at ambient temperature overnight.

[0384] The mixture is then precipitated with acetone and washed with methanol containing aqueous ammonia.

[0385] Synthesis of the Chloride Compound (1) of Formula:

##STR00020##

[0386] A mixture of 4-styrylpyridine (2.3 g, 12.5 mmol) (J. L. R. Williams, R. E. Adel, J. M. Carlson, G. A. Reynolds, D. G. Borden, J. A. Ford, J Org. Chem., 1963, 28, 387) and 1,2-dichloroethane (5 g, 50 mmol) was heated in the dark for 4 hours at 150 C. using an oil bath. The mixture was then dissolved by heating it in 30 ml of anhydrous ethanol and then cooled to 5 C.

[0387] The precipitate obtained was filtered off, washed with chloroform and air-dried.

EXAMPLE 2

Synthesis of Starch Grafted with Stilbazolium Groups

[0388] 20 g of sodium sulfate and 1.5 g of sodium hydroxide are dissolved in 75 ml of water and heated to 40 C.

[0389] 50 g of corn starch (Farma CS 3757 sold by Corn products international) are rapidly added with stirring.

[0390] 4 g of chloride compound (1) are added while maintaining the pH above 11.6. The mixture is stirred for 24 hours at 40 C. The reaction is then cooled to ambient temperature and the pH is adjusted to 7 with hydrochloric acid.

[0391] The modified starch is then filtered and the filtrate is washed with water and air-dried.

EXAMPLE 3

Synthesis of Alginate Grafted with Stilbazolium Groups

[0392] 1 g of sodium alginate (Kelcosol NF sold by FMC corporation) is dissolved in 100 ml of water. The pH of the solution is then adjusted to 11.6 with sodium hydroxide.

[0393] 0.1 g of chloride compound (1) dissolved in 1 ml of water is added to the reaction medium while maintaining the pH at 11.6. The mixture is stirred for 24 hours at 40 C. and then cooled to ambient temperature and the pH is adjusted to 7 with hydrochloric acid.

[0394] The mixture is precipitated with acetone, and the precipitate is washed with methanol and then air-dried.

EXAMPLE 4

Synthesis of Chitosan Grafted with Stilbazolium Groups

[0395] The grafted chitosan is obtained in the same way as the alginate previously described, using chitosan (Chitoclear SC342 from Primex).

EXAMPLE 5

[0396] The following composition is prepared and is then packaged in a bottle under a sterile atmosphere.

TABLE-US-00001 Amount (% by Compounds weight) Polyvinyl alcohol with pendent N- 6.9 methylstyrylpyridium groups, in methyl sulfate salt form, sold by the company Polymer Science under the name PS22570 Distilled water 83.1 Rhamnose 5 Glycerol 5

[0397] This injectable composition is used for a treatment of wrinkled epidermis via the technique of injection with a syringe to a depth of 0.5 mm below the surface area.

[0398] The area to be treated is then lit by an imager with a first dominant wavelength in the visible range of 8.5 mW/cm.sup.2 for 120 s, i.e. approximately 1 J/cm.sup.2.

[0399] The whole of the area having received the composition is then lit by an imager with a second dominant wavelength in the UVA range of 12 mW/cm.sup.2 for 120 s.

[0400] The excess composition is eliminated by dabbing. After photo-polymerization of the injected polymer, a reduction in the wrinkles at the surface of the skin is observed.

[0401] Another embodiment is described hereinafter.

[0402] The injectable composition is used for a treatment of the epidermis via the technique of injection with a syringe to a depth of 0.3 mm below the surface area of a wrinkle, and the injection is carried out little by little while withdrawing the syringe.

[0403] The area to be treated (0.2 cm by 2 cm) is then lit by an imager with a 405 nm Led Laser pointer of 15 mW (from the company Global Laser) which is defocused so as to cover a surface of 0.40.4 cm (i.e. 0.16 cm.sup.2).

[0404] A device keeps the imager away from the skin.

[0405] A scan is performed (0.1 cm/s) in order to treat the area over the 2 cm of length of the wrinkle. Thus, a surface of 0.4 cm by 2 cm, i.e. 0.8 cm.sup.2, is treated.

[0406] The treatment lasts for 200 s, i.e. 4 J/cm.sup.2.

EXAMPLE 6

[0407] The following composition is prepared and is then packaged in a bottle under a sterile atmosphere:

TABLE-US-00002 Compounds Amount (%) Xanthan gum grafted with stilbazolium 5 groups (example 1) Distilled water 90 Glycerol 5

[0408] The resulting composition is used for a treatment of wrinkled epidermis in accordance with that described in example 5.

EXAMPLE 7

[0409] The following composition is prepared and is then packaged in a bottle under a sterile atmosphere:

TABLE-US-00003 Compounds Amount (%) Starch grafted with stilbazolium groups 5 (example 2) Distilled water 90 Glycerol 5

[0410] The resulting composition is used for a treatment of wrinkled epidermis in accordance with that described in example 5.

EXAMPLE 8

[0411] The following composition is prepared and is then packaged in a bottle under a sterile atmosphere:

TABLE-US-00004 Compounds Amount (%) Alginate grafted with stilbazolium 5 groups (example 3) Distilled water 90 Glycerol 5

[0412] The resulting composition is used for a treatment of wrinkled epidermis in accordance with that described in example 5.

EXAMPLE 9

[0413] The following composition is prepared and is then packaged in a bottle under a sterile atmosphere:

TABLE-US-00005 Compounds Amount (%) Chitosan grafted with stilbazolium 5 groups (example 4) Distilled water 90 Glycerol 5

[0414] The resulting composition is used for a treatment of wrinkled epidermis in accordance with that described in example 5.