Patent Publication Number: US-2005143345-A1

Title: Cosmetic scar management composition

Description:
The present invention relates to a composition which finds particular utility in scar management.  
      It has been known for some years that the cosmetic severity of tissue scarring as a result of medical treatment and/or injury can be greatly reduced by the application of a silicone-containing sheet to the skin&#39;s surface. The mode of action remains unclear.  
      The first silicone-containing sheets used in order to reduce the visual severity of tissue scarring, based on a rubber containing formulation, were developed approximately 25 years ago and met with limited success since they were difficult to use. These silicone rubber sheets were secured on the skin surface with adhesive tape thereby forming a sealed enclosure. Typically, the silicone rubber sheet would be secured in place for 30 days during which time the skin would ‘remodel’ itself to a large degree giving rise to a decrease in the cosmetic severity of the scar tissue.  
      Several theories have been postulated regarding the mode of action of the silicone layers. These include the moisture barrier properties of silicone, the leaching of low molecular weight silicone into the skin and the effect of the ionic content of the silicone.  
      Despite these silicone rubber sheets being expensive, they were widely used even though the location of their use on the skin surface was limited by their lack of flexibility.  
      The aforesaid silicone rubber sheets have since been replaced with softer self-adhesive silicone gel sheets, which possess a greater degree of flexibility by virtue of their polymeric oil-containing network structure. Therefore, although easier to apply, their use remains limited as a result of their sheet-like nature  
      More recently liquid silicone compositions have been introduced. These are supplied in a tube and are specifically designed to be applied to awkward areas of the skins surface. Example of said compositions include KELO-COTE(™) or with a roller ball applicator, CICACARE(™). Unlike the previously described sheets, which are intended to be worn for a period of approximately 30 days, these liquid silicone compositions require re-application every few hours as the silicone layer located over the wound is thinner. However, these compositions remain sticky and tack-y after application, some fail to dry, whilst others take 10 to 30 minutes to dry.  
      It is desirable therefore to provide a composition which delivers the aforesaid cosmetic scar severity reduction and which is more convenient to use.  
      According to a first aspect of the present invention there is provided a scar management composition comprising at least one silicone component, water and at least one thickening agent.  
      Advantageously, the composition of the present invention is in the form of a surprisingly stable gel Which is easy to manufacture and as such is suitable for application to all skin areas, but it is particularly useful for the application to areas to which it is difficult to apply sheet material.  
      By gel it is meant a viscous, at least partially rigid material which can be manipulated to form a thin film.  
      A further advantage of the composition of the present invention lies with its ability to deliver moisture to the wound immediately on application by virtue of the composition&#39;s water content, thus) eliminating the need, as is the case with prior art silicone-containing sheets, for moisture to develop under the sheet thus giving an immediate skin softening and moisturising effect. The water content of the compositions of the present invention ultimately results in a more efficient and effective treatment.  
      A still further advantage of the composition of the present invention is it&#39;s rapid drying time, typically of about 2 minutes, thereby eliminating the undesirable tack of previously used liquid compositions which have a much longer drying time, typically in the order of 10 to 30 minutes.  
      Surprisingly, the composition of the present invention results in a greater reduction in the visual severity of a scar than that seen with previous methods of scar management.  
      Accordingly, the composition of the present invention is not only much easier and quicker to use than its predecessors but results in a greater reduction in the visual severity of scar tissue.  
      The silicone component preferably constitutes from 0.01% to 80%, more preferably from 1% to 50% and most preferably from 5% to 30% by weight of the composition of the present invention.  
      Suitable silicone components for use in the composition of the present invention include any of the following eiher alone or in combination:—silicone, silicone oil, silicone fluids, silicone solvents, silicone gels, silicone grease, silicone elastomer, or cross polymer, silicone gum, silicone adhesive silicone emulsifier, silicone wax emulsifier and silicone copolymer.  
      Preferably, the silicone component of the present invention is a silicone elastomer and/or a silicone gum. Advantageously this gives rise to a composition having a longer wear time than currently available scar management products. Table 3, shows how the inclusion of silicone elastomer increases the wear time of the product.  
      The thickening agent(s) preferably constitutes from 0.01% to 50%, more preferably from 0.01% to 10%, still more preferably from 0.01% to 0.99% and most preferably fro, 0.01% to 0.75% by weight of the composition of the present invention.  
      Suitable thickening agents include any of the foilowing either alone or in combination:—polyaciylic acid thickeners such as Carbopol, polyacrylic acid derivatives, polsrvyl alcohol (PVA, PVOH), pobvyl pyrrolidine (PVP), PVP/PVA copolymer, hydroxyethyl cellulose, acrylatepolymer, alkyl acrylates cross copolymer, hydrolysed protein, cetearyl alcohol, plant polysaccharide, microbial polysaccharide, animal polysaccharide, carboxymethyl cellulose, methyl cellulose, alginate, chitin/chitosan, hyaluronic acid, collagen, pectin, gelatine, starch and starch copolymer.  
      Preferably water constitutes from 2% to 99.8%, by weight of the composition of the present invention.  
      Preferably the composition of the present, invention shall contain at least one volatile solvent and most preferably at least one volatile organic solvent, for example isopropyl alcohol (IPA), ethanol, methanol, acetone, low molecular weight silicone, cyclomethicone, volatile silicone or silicone solvent, ethoxydiglycol, hexane.  
      The said solvent may constitute from 0% to 80%, preferably from 5% to 80% and most preferably from 10.1% to 80% by weight, of the composition of the present invention.  
      Preferably the composition of the present invention shall comprise at least one neutralising agent which can be mineral and/or organic in nature. Any suitable base may be used, for example sodium hydroxide, potassium hydroxide, triethanolamine and any suitable inorganic base.  
      In addition to the foregoing the composition of the present invention may also comprise any of the following, either alone or in combination:—active agents such as antibacterial agents, surfactants, antimicrobial agents, essential oil skin occlusion agents, copolymer and skin moisturisers, skin healing agents, scar healing agents, growth factors, or any compound which effects the level of growth factors in the skin, wound or scar, herbal agents, plant oils, essential oils or other plant extracts.  
      According to a second aspect of the present invention therefore there is provided a method of preparing a scar management composition comprising mug together at least two formulations wherein the first formulation comprises water and at least one thickening agent and the second formulation comprises at least one silicone component.  
      The first formulation may be a viscous water-based hydrogel which is formed when water containing at least one thickening agent typically in total 1%, by weight, is vigorously stirred The resulting viscous hydrogel is subsequently neutralised using sodium hydroxide, for example. The first formulation may optionally contain at lest one silicone component. The fist formulation may also contain active agents such as antibacterial agents, antimicrobial agents and/or skin moisturising agents.  
      The second formulation may be a mixture of two independent parts.  
      The first part of the second formulation may comprise volatile organic solvent(s) and any organic solvent soluble components such as one or more skin moisturisers.  
      The second part of the second formulation may comprise any of the aforesaid silicone components along w any surfactant and copolymer.  
      During preparation of the composition of the present invention the first formulation may be added to the second formulation with vigorous mixing, again until a homogeneous hydrogel ensues.  
      In order that the present invention be more readily understood the composition of the present invention now will now be described further by way of example only with relation to the following examples: 
    
    
     EXAMPLE 1  
      Silmogen Masterbatch ethanol and nusil silicone grease were pre-mixed to form the first formulation as a homogeneous mixture.  
      Carbopol ultrex was added to water with continuous sting, furnishing the first formulation as a homogeneous hydrogel which was neutralised with 2% aqueous soluton of sodium hydroxide.  
      The first fomulation was then added to the second formulation with vigorous stirring to furnish a homogenous gel the composition of the present invention.  
                                           Formulation   Component   Function   Quantity                  First   Water   Solvent   200 g           Carbopol Ultrex   Thickening Agent    2 g           NaOH (2%   Neutralising Agent    2 wt %           solution)       of total comp. A       Second   Silmogen   Silicone    54 g           Masterbatch   Component           Ethanol   Organic Solvent    18 g           Nusil   Silicone Grease    6 g                 NB: Drying time (average of 3 tests) 93 seconds.             
 
     EXAMPLE 2  
      The composition was prepared in the aforesaid manner  
                                           Formulation   Component   Function   Quantity                  First   Water   Solvent    200 g           Carbopol 914   Thickening Agent     1.5 g           Neutrol TE   Neutralising Agent   to pH 7       Second   Ethanol   Organic Solvent    100 g           Silmogen Carrier   Silicone Solvent    100 g           Dimethicone Blend   Silicone   20-25 g               Component                 NB: Drying time 23 seconds.             
 
     EXAMPLE 3  
      The composition was prepared in the aforesaid manner  
                                           Formulation   Component   Function   Quantity                  First   Water   Solvent    190 g           Medical Grade   Moisturising     10 g           Aloe Vera Gel   Agent           Carbopol 914   Thickening Agent     5 g           Neutrol TE   Neutralising Agent   to pH 7       Second   Ethanol   Organic Solvent    200 g           Silmogen Carrier   Silicone Solvent    125 g           Dimethicone Blend   Silicone   20-75 g               Component                 NB: Drying time 98 seconds.             
 
     EXAMPLE 4  
      The composition was prepared in the aforesaid manner  
                                           Formulation   Component   Function   Quantity                  First   Water   Solvent    200 g           Carbol 914   Thickening Agent     5 g           Salicylic Acid   Antibacterial     0.5 g               Agent           Neutrol TE   Neutralising Agent   to pH 7       Second   Ethanol   Organic Solvent    200 g           Silmogen Carrier   Silicone Solvent    125 g           Dimethicone Blend   Silicone   20-75 g               Component                 NB: Drying time - not available.             
 
     EXAMPLE 5  
      The composition was prepared in the aforesaid manner  
                                           Formulation   Component   Function   Quantity (g)                                                First   Water   Solvent   247.55           Ethanol   Organic Solvent   108.35           Carbopol 980NF   Thickener   3.20           Nipagin M   Preservative   0.29           Nipasol M   Preservative   0.07       Second   Elastomer 10   Silicone   33.85               component           Cyclomethicone 5   Silicone   22.44               component           Isopropyl   Solubilising agent   4.25           Myristate                 The composition was neutralised to between pH 7.3 and 7.6 using sodium hydroxide.            N.B. Drying time 80 seconds.             
 
     EXAMPLE 6  
      The composition was prepared in the aforesaid manner  
                                           Formulation   Component   Function   Quantity (g)                                                First   Water   Solvent   247.55           Ethanol   Organic Solvent   108.35           Carbopol 980NF   Thickening Agent   4.6           Nipagin M   Preservative   0.29           Nipasol M   Preservative   0.07       Second   Dow Corning   Silicone   56.5           silicone fluid   component                 Drying time - not available.             
 
     EXAMPLE 7  
      Unlike the previous examples the composition described below does not contain any organic solvents.  
      Carbopol 940 was added to water, with vigorous siring. The resulting hydrogel was neutralised using sodium hydroxide, thus furnishing the first formulation.  
      The first formulation was then stirred vigorously while dimethicone blend 20, the second formulation, was introduced.  
      The resulting gel was mixed for a three minutes providing the composition of the present invention.  
                                           Formulation   Component   Function   Quantity                  First   Water   Solvent   200 g           Carbopol 940   Thickening Agent    1.5 g           NaOH   Neutralising Agent   to pH 7       Second   Dimethicone blend   Silicone    20 g           20   Component                 NB: Drying time 435 seconds.             
 
     EXAMPLE 8  
      In addition to the components of examples 1 to 4the composition described below contains emulsifiers.  
      Carbopol 980 was added to water. This mixture was then pre-heated to 50° C. and a mixture of stearyl alcohol and trimethylstearyloxysilane was introduced providing the first formulation as an emulsion, which was then allowed to cool.  
      Dimethicone blend 20 and ethanol were mixed together resulting in the second formulation.  
      The second fomulation was then introduced to a vigorously stirred first formulation.  
                                           Formulation   Component   Function   Quantity                  First   Water   Solvent   168 g           Carbopoly 980   Thickening Agent    2 g           Silky wax 10 (a   Silicone component    2 g           mixture of stearyl           alcohol and           trimethylstearyloxy           silane)       Second   Ethanol   Organic Solvent   10% of                   component                   phase A           Dimethicone blend 20   Silicone Component   10% of                   component                   phase A                 NB: Drying time 360 seconds.             
 
      Clinical cast studies have been performed to assess the effectiveness of the scar management compositions of the present invention.  
      In the following case study the patient was asked using the guidelines exemplified in Table 1, to comment as to the appearance and feel of each scar following treatment with compositions described herein.  
                   TABLE 1                       Questions   Results                  1. Has the scar improved since the last assessment?   Yes or No       2. Rate its appearance on a scale of 1 to 5   1 to 5          (with 1 as the best and 5          as the worst)?       3. Rate its flexibility on a scale of 1 to 4   1 to 5          (with 1 as the best and 5          as the worst)?       4. Rate its softness on a scale of 1 to 5   1 to 5          (with 1 as the best and 5 as          the worst)?       5. Does it feel irritated? Rate this   1 to 5          on a scale of 1 to 5 (with 1 as the          best and 5 as the worst)?       6. Is it better or worse than the scar it   Better or Worse          was originally paired against?                  
 
 Case Study 
 
      A patient had four fatty cysts surgically removed from under the surface layer of the skin on the arm Following surgery the wounds were-sutured closed and dressings with Jelonet™ and a gauze bandage were applied thereto, The patient was asked to minimise the movement of the arm and keep it elevated for 24 hours after the operation.  
      The sutures were removed 10 days after surgery.  
      Three days after the removal of the sutures the scars appeared dry and red.  
      The patient was asked to apply a scar management composition according to the present invention to two of the scars (scar 1 and scar 3) each morning and after every bath or shower.  
      The other two scars (scar 2 and scar 4) were not treated.  
      The scars were assessed 12 days, 26 days and 68 days from the first treatment.  
      The results of the clinical case study are shown in Table 2.  
                           TABLE 2                          Ques-   After 12 days   After 26 days   After 68 days                                                                 tion   scar 1   scar 2   scar 3   scar 4   scar 1   scar 2   scar 3   scar 4   scar 1   scar 2   scar 3   scar 4               1.   Yes   Yes   Yes   Yes   Yes   No,   Yes   No, it got   Yes   No   Yes   No                               maybe       worse, more                               slightly       red and more                               softer       raised       2.   3   3   4   5   2   3   3   5   1   3   2   5       3.   2   4   3   3   1   3   2   2   1   2   1   3       4.   2   4   3   3   1   3   2   2   1   2   1   3       5.   3   3   2   4   1   2   1   5   1   2   1   4       6.   Very   Very   Same   Same   Better in   Worse in   Considerably   Considerably   Considerably   Worse in   Considerably   Considerably           slightly   slightly   as   as   colour and   colour and   better than   worse than   better in   colour and   better than   worse than           better   worse   scar 4   scar 3   softness/   softness/   scar 4 in   scar 3 in   colour and   softness/   scar 4 in   scar 3 in           than   than           flexibility   flexibility   colour   colour,   softness/   flexibility   colour,   colour,           scar 2   scar 1           than scar 2   than scar 1       height and   flexibility   than scar 1   height and   height and                                       irritation   than scar 2       irritation   irritation                  
 
                                 TABLE 3                                      Elastomer               or gum   Wear Time (hours)                                                     Example   Format   present?   1   2   4   6   8   10   12               Competitor   —   Neither   Pass   Pass   Fail                       Product       Kelocote ™       (control)       Example 6   Hydrogel   Neither   Pass   Pass   Fail       Example 5   Hydrogel   Elastomer   Pass   Pass   Pass   Pass   Pass   Pass   Fail                    
 Test Method Summary 
 
 0.07 g of test material is applied to a 5 cm 2  area of skin. 
 
      The area is wetted with water after 1 hour, 2 hours, 4 hours and then every 2 hours.  
      The product ‘passes’ if the water after forms an elevated bubble indicated that a significant amount of silicone is still present.  
      The product ‘fails’ if the water does not form a elevated bubble indicated that little if any silicone is still present.  
      It is of course to be understood that the invention is not intended to be restricted to the details of the above embodiments which are described by way of example only.