Composition for covering and protecting scars

Abstract

Subject of the invention is a composition comprising: (a) at least one film-forming polymer, which does not comprise silicon, (b) at least one organic UV filter, and (c) at least one organic solvent, wherein the composition is liquid at 20 C., wherein components (a) and (b) are dissolved in solvent (c), and wherein the ratio of the total amounts of organic UV filters (b) to film-forming polymers (a) is below 6.5. The invention also relates to compositions for therapy, uses of the composition, devices and methods.

Claims

1. A composition comprising (a) at least one film-forming polymer, which does not comprise silicon, (b) at least one organic UV filter, and (c) at least one organic solvent, wherein the composition is a liquid solution at 20 C. with no solids dispersed therein, wherein components (a) and (b) are dissolved in solvent (c), wherein the ratio of the total amounts in weight percent of organic UV filters (b) to film-forming polymers (a) is below 6.5, wherein the overall amount of UV filters (b) in the composition is at least 10% (w/w), wherein the composition comprises at least 5% (w/w) of film-forming polymers (a), wherein the composition forms a solid coating after topical application to skin, wherein the composition does not comprise other polymers than the film-forming polymers (a), and wherein the composition does not comprise a silicone.

2. The composition of claim 1, wherein the film-forming polymer (a) is an amphiphilic copolymer.

3. The composition of claim 1, wherein the film-forming polymer (a) is an acrylate/amide copolymer with alkyl groups having 6 to 16 carbon atoms.

4. The composition of claim 1, wherein the composition comprises less than 5% (w/w) water, and/or wherein the ratio of the total amounts in weight percent of organic UV filters (b) to film-forming polymers (a) is above 1 to below 6.5.

5. The composition of claim 1, wherein the solvent (c) is an aliphatic alcohol, and/or wherein the composition comprises at least one additive (d).

6. The composition of claim 1, consisting of (a) between 5 and 50% (w/w) film-forming polymers, which do not comprise silicon, (b) between 10 and 60% (w/w) organic UV filters, (c) between 30 and 90% (w/w) organic solvents, (d) between 0 to 25% (w/w) additives, and less than 5% (w/w) water.

7. The composition of claim 1, wherein the composition forms a solid coating after topical application to a scar.

8. The composition of claim 1, wherein the composition has a sun protection factor (SPF) of at least 10.

9. A method for covering a scar, the method comprising (A) providing a composition of claim 1, (B) applying the composition locally and topically to a scar of an individual, and (C) optionally drying the composition.

10. A method for preparing a composition of claim 1, comprising the steps of (i) dissolving the film-forming polymers (a) in the organic solvent (c) to obtain phase A, (ii) providing the UV filters (c) in liquid form, optionally at enhanced temperature, as a phase B, and (iii) mixing phase A and phase B.

11. A device for topical application of a composition of claim 1 to the skin of an individual, wherein the device comprises a composition of claim 1.

12. The method of claim 9, wherein the method is non-therapeutic.

13. The method of claim 9, wherein the method supports healing of the scar.

14. The composition of claim 2, wherein the copolymer comprises carboxyl groups and alkyl groups and wherein the carboxyl groups are attached to the polymer main chain and the alkyl groups are side chains.

15. The composition of claim 3, wherein the acrylate/amide copolymer is an acrylate/octylacrylamide copolymer.

16. The composition of claim 5, wherein the solvent (c) is methanol, ethanol, propanol or isopropanol, and/or wherein the composition comprises at least one additive (d), which is selected from moisturizers, photoprotective agents, oils, fats, waxes, glycerides, surfactants, thickening agents, fragrances, dyes, preservatives, photostabiliziers, antioxidants, skin care agents and pharmaceutical agents.

17. The composition of claim 7, wherein the composition forms a solid coating after topical application to a scar within less than 1 minute.

18. The composition of claim 8, wherein the composition has a sun protection factor (SPF) of at least 40.

19. The method of claim 10, wherein mixing phase A and phase B comprises adding phase B to phase A.

20. The device of claim 11, wherein the device is in the form of a roller.

21. The composition of claim 1, which comprises between 0 to 10% (w/w) additives.

22. A composition consisting of (a) between 5 and 50% (w/w) film-forming polymers, which do not comprise silicon, (b) between 10 and 60% (w/w) organic UV filters, (c) between 30 and 90% (w/w) organic solvents, (d) between 0 to 25% (w/w) of at least one additive, and less than 5% (w/w) water, wherein the composition is a liquid solution at 20 C. with no solids dispersed therein, wherein components (a) and (b) are dissolved in solvent (c), wherein the ratio of the total amounts in weight percent of organic UV filters (b) to film-forming polymers (a) is below 6.5, wherein the composition forms a solid coating after topical application to skin, wherein the at least one additive is selected from photoprotective agents, hydrophobic compounds selected from fats and waxes; surfactants, thickening agents, fragrances, dyes, preservatives, photostabilizers, antioxidants and pharmaceutical compounds, and wherein the composition does not comprise a silicone.

23. The composition of claim 22, wherein the film-forming polymer (a) is an amphiphilic copolymer.

24. The composition of claim 22, wherein the film-forming polymer (a) is an acrylate/amide copolymer with alkyl groups having 6 to 16 carbon atoms.

25. The composition of claim 22, wherein the ratio of the total amounts in weight percent of organic UV filters (b) to film-forming polymers (a) is above 1 to below 6.5.

26. The composition of claim 22, wherein the solvent (c) is an aliphatic alcohol, and/or wherein the composition comprises at least one additive (d).

27. The composition of claim 22, wherein the composition forms a solid coating after topical application to a scar.

28. The composition of claim 22, wherein the composition has a sun protection factor (SPF) of at least 10.

Description

EXAMPLES

Example 1

(1) TABLE-US-00001 TABLE 1 Composition example 1 INCI Name (trade name, Dosage Pos. manufacturer) CAS Number [%, .sup.w/.sub.w] Function 1 alcohol 64-17-5 55.0 solvent (--, Alcosuisse) 2 acrylates/ 129702-02-9 15.0 film-forming octylacrylamide polymer copolymer (Dermacryl 2.0, AkzoNobel) 3 octocrylene 6197-30-4 10.0 UV filter (Parsol 340, DSM) 4 isoamyl-p- 71617-10-2 10.0 UV filter methoxycinnamate (Neo Heliopan E1000, Symrise) 5 diethylamino 302776-68-7 10.0 UV filter hydroxybenzoyl hexyl benzoate (Uvinul A Plus, BASF)
Preparation
Phase A Add the solvent (Pos. 1) into a receiving vessel. Add the polymer (Pos. 2) to the solvent (Pos 1) and start to stir. Continue to stir at ambient temperature until a clear and homogenous liquid is obtained.
Phase B Add the UV filters (Pos. 3, Pos. 4 and Pos. 5) into a separate vessel and start to stir. Heat up to max. 65 C. and continue to stir until a clear and homogenous liquid is obtained.
Composition

(2) Add phase B to phase A and mix by stirring at room temperature until a clear, slightly viscous and homogenous liquid is obtained, which had a viscosity (20 C.) of 98 mPas and a density (20 C.) of 0.912 g/cm.sup.2.

(3) Administration and Product Properties

(4) Using a roll-on, a brush or another suitable applicator the slightly viscous Polymer-UV filter solution can be easily administered onto a scar. Shortly after application the solvent evaporates and a thin coating is formed. The coating is solid and elastic. It is water-resistant, non-tacky and hard to rub off. The formed coating is occlusive and protects the scar from UV radiation.

Example 2

(5) TABLE-US-00002 TABLE 2 Composition example 2 INCI Name (trade name, Dosage Pos. manufacturer) CAS Number [%, .sup.w/.sub.w] Function 1 alcohol 64-17-5 60.0 solvent (--, Alcosuisse) 2 acrylates/ 129702-02-9 15.0 film-forming octylacrylamide polymer copolymer (Dermacryl 2.0, AkzoNobel) 3 octocrylene 6197-30-4 10.0 UV filter (Parsol 340, DSM) 4 isoamyl-p- 71617-10-2 10.0 UV filter methoxycinnamate (Neo Heliopan E1000, Symrise) 6 butyl 70356-09-1 5.0 UV filter methoxydibenzoyl- methane (Parsol 1789, DSM)

(6) The preparation was carried out in a way that is analogous to example 1. The properties of the coating were essentially as described in example 1.

Example 3

(7) TABLE-US-00003 TABLE 3 Composition example 3 INCI Name Dosage Pos. (trade name, manufacturer) CAS Number [%, .sup.w/.sub.w] Function 1 alcohol 64-17-5 61.0 solvent (, Alcosuisse) 2 acrylates/octylacrylamide copolymer 129702-02-9 15.0 film-forming polymer (Dermacryl 2.0, AkzoNobel) 3 octocrylene 6197-30-4 8.0 UV filter (Parsol 340, DSM) 4 isoamyl-p-methoxycinnamate 71617-10-2 8.0 UV filter (Neo Heliopan E1000, Symrise) 5 diethylamino hydroxybenzoyl hexyl benzoate 302776-68-7 8.0 UV filter (Uvinul A Plus, BASF)

(8) The preparation was carried out in a way that is analogous to example 1. The properties of the coating were essentially as described in example 1.

Example 4

(9) TABLE-US-00004 TABLE 4 Composition example 4 INCI Name (trade name, Dosage Pos. manufacturer) CAS Number [%, .sup.w/.sub.w] Function 1 alcohol 64-17-5 66.0 solvent (--, Alcosuisse) 2 acrylates/ 129702-02-9 15.0 film-forming octylacrylamide polymer copolymer (Dermacryl 2.0, AkzoNobel) 3 octocrylene 6197-30-4 7.0 UV filter (Parsol 340, DSM) 4 isoamyl-p- 71617-10-2 7.0 UV filter methoxycinnamate (Neo Heliopan E1000, Symrise) 6 butyl 70356-09-1 5.0 UV filter methoxydibenzoyl- methane (Parsol 1789, DSM)

(10) The preparation was carried out in a way that is analogous to example 1. The properties of the coating were essentially as described in example 1.

Example 5

(11) TABLE-US-00005 TABLE 5 Composition example 5 INCI Name Dosage Pos. (trade name, manufacturer) CAS Number [%, .sup.w/.sub.w] Function 1 alcohol 64-17-5 57.6 solvent (, Alcosuisse) 2 ethyl ester of PVM/MA copolymer 25087-06-3 20.0 film-forming (Gantrez SP 215, Ashland) polymer 3 octocrylene 6197-30-4 10.0 UV filter (Parsol 340, DSM) 4 isoamyl-p-methoxycinnamate 71617-10-2 7.4 UV filter Neo Heliopan E1000, Symrise) 6 butyl methoxydibenzoylmethane 70356-09-1 5.0 UV filter (Parsol 1789, DSM)

(12) The preparation was carried out in a way that is analogous to example 1. The properties of the coating were essentially as described in example 1, but the water resistance of the coating was not as good as the one of example 1.

Example 6

(13) A composition was prepared essentially according to example 1, but the film-forming polymer was hydrogenated dimer dilinoleyl/dimethylcarbonate copolymer (BASF, DE, trademark COSMEDIA DC) instead of Dermacyrl 2.0. The properties of the coating were essentially as described in example 1, but the coating was found to be tacky.

Examples 7 to 11

(14) The influence of the ratio of UV-filters to film-forming polymers on the coating characteristics was studied in a series of experiments. The properties of various alcoholic solutions containing equal amounts UV-filters but different amounts of the polymer Dermacryl 2.0 were assessed. The formulations of examples 7 to 11 were prepared as described in example 1, but the amount of polymer was changed. The amount of ethanol was adapted to the change of polymer. Examples 7 to 10 are inventive and example 11 is comparative. The changes compared to example 1 and the results obtained are summarized in the following table.

(15) TABLE-US-00006 TABLE 6 Compositions of examples 1 and 7 to 11 Dermacryl 2.0 Ethanol Ex. [wt. %] [wt. %] Ratio* Film Characteristics 1 15.0 55 2.0 clear firm and elastic feel tack-free adhesion excellent skin substantivity and persistency water and rub-off resistant suitable for applying cosmetics to conceal the scar 7 12.5 57.5 2.4 as ex. 1 8** 10.0 60 3.0 as ex. 1 9 7.5 62.5 4.0 as ex. 1 10 5.0 65 6.0 clear slightly oily slightly tacky good skin substantivity and persistency water resistant partially removable limited suitability for permanently applying cosmetics to conceal the scar 11 4.5 65.5 6.7 oily and greasy feel easy to remove not suitable for permanently applying cosmetics to conceal the scar *total UV-filters to polymer weight ratio **viscosity determined to be about 36 mPas

(16) The results show that alcoholic solutions, which are containing equal amounts of UV-filters but varying amounts of the polymer Dermacryl 2.0, exhibit different coating forming properties. Formulations containing 7.5% or more of the polymer form clear, firm, elastic and tack-free coatings exhibiting good skin substantivity and persistency. The coatings are water and rub-off resistant. In contrast, the solution containing only 4.5% of the polymer forms a clear film with an oily feel. The coating can be easily removed. From the data, it can be deduced that a UV-filter to polymer ratio of less than 6.7, preferably less than 6, is required for obtaining coatings with the desired characteristics for scar treatment: clear, firm, elastic, tack-free, occlusive, good skin substantivity, water and rub-off resistant. This ratio might be slightly different depending on the UV-filter combination used and should be evaluated for each set of UV-filters.

Examples 12 to 19UV Protection, Application and Stability of Coating

(17) The UV protection properties, application and mechanical stability of an inventive coating of a composition according to example 8 above were analyzed. For comparison, the same methods were carried out under identical conditions with a commercial scar protection product available under the trademark KELO-COTE UV from Sinclair Pharma, DE. This silicone based scar gel is the market leader for scar and UV protection and thus a suitable benchmark product for direct comparison.

Examples 12 to 15Mean Sun Protection Factor SPF

(18) The mean sun protection factor (SPF) was determined according to DIN EN ISO 24444:2010, a method for the in vivo determination of the sun protection factor of sunscreen products. It is applicable to products that contain any component able to absorb, reflect or scatter UV rays and which are intended to be placed in contact with human skin. This international standard provides a basis for the evaluation of sunscreen products for the protection of human skin against sunburn induced by solar ultraviolet rays. The level of sun protection provided by sunscreen products has traditionally been estimated using the sun protection factor or SPF test, which uses the erythemal response of the skin to UV radiation. The SPF is a ratio calculated from the energies required to induce a minimum erythemal response with and without sunscreen product applied to the skin of human volunteers. It uses ultraviolet radiation usually from an artificial source. The test was carried out with 10 individuals. Results were determined 30 min and 8 h after application to the skin. The results complied with statistical criteria set forth by the SPF-test method EN ISO 24444:2010.

(19) The results are summarized in table 7 below. The results show that the inventive product has a very high SPF of 50 (example 12). Strong protection is still provided 8 hours after application to the skin (example 13). The UV protection properties are significantly better than for the benchmark product (comparative examples 14, 15).

(20) TABLE-US-00007 TABLE 7 Results of examples 12 to 15. Examples 14 and 15 are comparative labelled applica- protec- 95% stan- tion time tion confi- dard compo- before labelled cate- dence SPF devia- Ex. sition measuring SPF gory interval mean tion 12 exam- 30 min 50 high 49.3-54.3 51.8 3.5 ple 8 13 exam- 8 h 30 high 28.2-32.6 30.4 3.0 ple 8 14 Kelo- 30 min 39 high 29.1-32.4 30.7 2.3 Cote UV 15 Kelo- 8 h 20 medium 18.5-23-2 20.8 3.3 Cote UV

Examples 16 and 17Protection Against UVA and Critical Wavelength

(21) The UVA-protection was assessed according to ISO 24443:2012 Determination of sunscreen UVA photoprotection in vitro. The standard is for determining UVA-protection provided by sun-screen products. The method determines in-vitro UVA-protection factor (UVAPF) in correlation to the labeled UVB-protection factor. The test is based on is measuring UV-transmittance through a thin film of the sunscreen sample spread on a roughened substrate, before and after exposure to a controlled dose of UV-radiation from a defined UV-source. For irradiation, a dose of UV-light is chosen specified for the product on test.

(22) The critical wavelength .sub.c was determined according to the Critical wavelength values of sunscreen products published by the COLIPA in-vitro UV Protection Method Task Force of (March 2011). The critical wavelength .sub.c value for the test product is defined as that wavelength up to which the area under the absorbance spectrum for the irradiated product from 290 nm is 90% of the integral of the absorbance spectrum from 290 nm to 400 nm. The test is based on measuring UV-transmittance through a thin film of sunscreen sample spread on a roughened substrate, before and after exposure to a controlled dose of UV-radiation from a defined UV-source. For irradiation a dose of UV-light is chosen specified for the product on-test. The critical wavelength is considered to be a measure of the breadth of sunscreen protection. Filters are then classified as broad spectrum, having a significant part of their absorbance in the UVA, when the critical wavelength is longer than 370 nm.

(23) The results are summarized in table 8 below. The results show that the UVA protection of the inventive product in example 16 is about 45.5%, whereas UVA protection of the comparative product is only 4.2%. According to industry standards, only the inventive composition may be labelled as UVA protective. Further, the critical wavelength of the inventive composition is significantly higher which indicates that the composition provides broad spectrum protection.

(24) TABLE-US-00008 TABLE 8 Results of example 16 and comparative example 17 UVA critical labelled dose number wave- compo- SPF used UVAPF/ of length Ex. sition in vivo [J/cm.sup.2] UVAPF SPF plates .sub.c [nm] 16 exam- 50 28.0 22.73 0.455 4 377 ple 8 17 Kelo- 30 1.58 1.26 0.042 4 330 Cote UV

Example 18Scar Healing

(25) A double blind, placebo controlled, randomized clinical study was carried for assessment of efficacy of the inventive composition in the treatment of hypertrophic, keloid or cosmetically unsatisfactory scars. The trial was carried out with a POSAS questionnaire.

(26) The Patient and Observer Scar Assessment Scale (POSAS) is a questionnaire to assess scar quality. The POSAS is widely used and accepted in the technical field and has been used for a large number of clinical trials. It consists of two separate six-itemed scales, observer and patient scale which based on the 10-point system. The observer scale has vascularity, pigmentation, thickness, relief, pliability, and surface area criterions. The observer scale of the POSAS consists of six items (vascularity, pigmentation, thickness, relief, pliability and surface area). All items are scored on a scale ranging from 1 (like normal skin) to 10 (worst scar imaginable). The sum of the six items results in a total score of the POSAS observer scale. Categories boxes are added for each item. Furthermore, an overall opinion is scored on a scale ranging from 1 to 10. All parameters should preferably be compared to normal skin on a comparable anatomic location. The patient scale comprises six standard questions to be answered by the patient. The answers are given on a scale from 1 to 10. Further information regarding the questionnaire can be found at www.posas.org.

(27) POSAS was carried out in a placebo controlled double blind study with intra-individual control with patients having chirurgical scars. The study was carried out with 8 patients having scars of a length of at least 2 cm. Two comparable scars each were treated with an inventive composition of example 8 above. For comparison, patients were treated with the commercially available scar gel KELO-COTE UV from Sinclair, DE, which is the market leader and benchmark product. Overall, 5 patients were treated with the inventive product and 3 patients with the comparative product, the discrepancy being due to random selection of the probe in the trial. The individuals applied the gel twice a day over a time span of three months. The scars were evaluated according to the POSAS scale by the doctor and patient 1 day before first application, after 6 weeks and after 3 months. The trial was carried out according to the principles of the declaration of Helsinki (World medical association 2000) and the rules of Good Clinical Practice (ICH 1998). The results are summarized in table 9 (observer scale) and 10 (patient scale).

(28) TABLE-US-00009 TABLE 9 POSAS observer scale, criteria and results after 3 months. Possible results range from 1 = normal skin to 10 = worst imaginable scar coating Kelo- parameter explanation inventive Cote UV vascularity Presence of vessels in scar 1.4 5.3 tissue assessed by the amount of redness, tested by the amount of blood return after blanching with a piece of Plexiglas pigmentation Brownish coloration of the 1.6 5.3 scar by pigment (melanin); apply Plexiglas to the skin with moderate pressure to eliminate the effect of vascularity thickness Average distance between the 2.0 6.0 subcutical-dermal border and the epidermal surface of the scar relief The extent to which surface 2.0 6.0 irregularities are present (preferably compared with adjacent normal skin) pliability Suppleness of the scar tested 1.4 6.3 by wrinkling the scar between the thumb and index finger surface area Surface area of the scar in 2.0 5.7 relation to the original wound area Overall 1.6 6.0 opinion

(29) The results provide evidence of a significant effect of the inventive product on scar healing. For all patients treated with the inventive product, after 3 months the scars were healed completely or almost completely and the respective skin portion was identical or highly similar to normal skin. Notably, most patients already reported significant improvements after a few weeks (data not shown). In contrast, all patients treated with the benchmark product for 3 months still had pronounced scars.

(30) TABLE-US-00010 TABLE 10 POSAS patient scale, questions and results after 3 months coating Kelo- Question inventive Cote UV possible answers ranging from 1 = no, not at all to 10 = yes, very much has the scar been painful the past few weeks? 1.2 3.0 has the scar been itching the past few weeks? 1.0 4.7 possible answers ranging from 1 = no, as normal skin to 10 = yes, very different is the scar color different from the color of your 2.0 6.7 normal skin at present? is the stiffness of the scar different from your 2.0 7.3 normal skin at present? is the thickness of the scar different from your 1.8 7.3 normal skin at present? is the scar more irregular than your normal skin 2.0 7.3 at present? possible answers ranging from 1 = as normal skin to 10 = very different what is your overall opinion of the scar compared 1.6 7.0 to normal skin?

(31) The patients results demonstrate confirm the significant effect of the inventive coating on scar healing. In contrast, all patients treated with the benchmark product reported pronounced scars after 3 months.

Example 19: Ease of Application and Mechanical Stability of Coating

(32) Together with the POSAS questionnaire described above in example 18, additional questions were asked to the patients relating to application and stability of the dried products on the scars. Thus, the supplementary questionnaire was part of the double blind, placebo controlled, randomized clinical study. The questions and results are summarized in the following.

(33) A) How fast did the gel dry?

(34) All patients treated with the inventive composition reported drying within 10 to 40 seconds. In contrast, all patients treated with the benchmark product reported that drying requires more than 30 minutes.

(35) B) Is the gel film undamaged despite movement or dressing?

(36) All patients treated with the inventive composition answered yes. In contrast, the patients treated with the benchmark product answered no.

(37) C) How is stability of the gel film upon contact with water/moisture?

(38) The patients treated with the inventive composition answered that the stability is very good (4 patients) or good (1 patient). In contrast, all patients treated with the benchmark product answered that the stability is unsufficient.

(39) D) For how long does the gel film remain on the skin?

(40) All patients treated with the inventive composition reported that the film remained on the skin for at least 6 hours or at least 8 hours. In contrast, all patients treated with the benchmark product reported that the film remained on the skin for less than 60 minutes.
E) Is the gel film applied in the morning still present at the application time in the evening?
All patients treated with the inventive composition reported that 100% or about 50% or the film was still present. In contrast, all patients treated with the benchmark product reported that the film was not present any more or that about 30% was still present.

(41) Overall, the results demonstrate that the inventive composition is applied much more conveniently and far more stable on the skin. From the data it can be deduced that only the inventive coating is suited for convenient regular use and normal activities. It provides long-term protection for up to 8 hours and does not compromise typical activities of the user such as dressing, standard outdoor activities or contact with moisture by rain, washing or sweating. Moreover, the inventive coating can be applied again conveniently in because of the rapid drying time of less than 1 minute. In contrast, the benchmark product has a low stability and frequent application is unpractical because of the time required for drying.

(42) In contrast, the benchmark product has a very limited stability and becomes ineffective upon contact with moisture or moderate mechanical stress. Frequent application is unpractical in view of the long drying time.