DRESSING FORMULATIONS TO PREVENT AND REDUCE SCARRING

Abstract

Provided herein is a scar dressing formulation comprising a blend of a high molecular weight silicone elastomer crosspolymer and a silicone oil, wherein said silicone elastomer crosspolymer is in a volatile fluid. The formulation has a soft, silky feel without being greasy and dries quickly to form a durable, flexible scar dressing.

Claims

1. A scar dressing formulation comprising a high molecular weight, low viscosity silicone crosspolymer in a volatile fluid; and a silicone fluid/oil.

Description

MODES OF CARRYING OUT THE INVENTION

[0013] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of ordinary skill in the art to which this invention belongs. All patents, applications, published applications and other publications referred to herein are incorporated by reference in their entirety. If a definition set forth in this section is contrary to or otherwise inconsistent with a definition set forth in the patents, applications, published applications and other publications that are herein incorporated by reference, the definition set forth in this section prevails over the definition that is incorporated herein by reference.

[0014] As used herein, “a” or “an” means “at least one” or “one or more.”

[0015] Silicones are a group of completely synthetic polymers containing the recurring group —SiR.sub.2O—, wherein R is a radical such as an alkyl, aryl, phenyl or vinyl group. The simpler silicones are oils of very low melting point, while at the other end of the scale of physical properties are highly crosslinked silicones which form rigid solids. Intermediate in physical properties between these two extremes are silicone elastomers such as gels and rubbers. When the silicones are formed by crosslinking a mixture of two or more silicones, the molecular weights of the various components and/or their degree of substitution by reactive groups may be different. This allows mixtures having different physical properties to be formed merely by varying the proportions of the components.

[0016] Provided herein is a scar (or wound) dressing comprising a blend of a high molecular weight silicone elastomer crosspolymer and a silicone oil, wherein said silicone elastomer crosspolymer is in a volatile fluid. The silicone elastomer crosspolymer can be dimethicone-based or a blend of cylclohexasiloxane and cyclopentasiloxane. The silicone oil can be dimethicone, cyclomethicone or a mixture thereof. The silicone elastomers useful in the wound dressing provided are those that dry quickly, have a soft, silky feel on the skin and add a luxurious texture to dressing when initially applied. The scar dressing provided herein can be occlusive and flexible. The dressings are non-tacky and non-greasy.

[0017] Any suitable high molecular weight silicone elastomer may be employed. A silicone elastomer comprises crosslinked silicone polymers. The use of crosslinked silicone polymers eliminates the need for a catalyst or crosslinking agent in the scar dressing formulation. In some embodiments, the preferred molecular weight of the elastomer depends upon the desired viscosity of the scar dressing formulation as well as the desired characteristics of quick drying, conformity, texture, and non-tackiness. Exemplary elastomers include dimethicone crosspolymers as in Dow Corning® 9040 (dimethicone crosspolymer) or KSG-210 (dimethicone/PEG-10/15 crosspolymer and dimethicone) (ShinEtsu Chemical Co. Ltd) as well as Volasil 7525 (a blend of cyclopentasiloxane and cyclohexasiloxane) (Chemisil Silicones Inc.). Typically, the high molecular weight elastomer crosspolymer has a low viscosity of about 50 cSt or less, about 25 cSt or less, or sometimes 5 cSt or less.

[0018] The silicone elastomer is in a volatile fluid. In most embodiments, the non-volatile component is less than about 10%, less than about 15%, less than about 20%, or less than about 30% by weight. Volatile fluids include super low viscosity silicone fluids such as cyclomethicone or dimethicone. The silicone elastomer in a volatile fluid represents greater than about 70%, about 80%, greater than about 85%, greater than about 90%, or greater than 95% by weight of the wound dressing formulation.

[0019] The silicone oils useful in the wound dressing formulation provided herein have a high nonvolatile content of greater than 70%, greater than 80% or greater than 90%. Exemplary silicone oils include dimethicone, cyclomethicone or a mixture thereof such as Botanisil S-19 (PEG-12 dimethicone). The silicone oil can be in a fluid or powder form. In one embodiment, the silicone oil can be a dimethicone/vinyl dimethicone crosspolymer such as Dow Corning® 9506. The amount of silicone oil in the scar dressing formulation can be from about 0.5% to about 15% of the blend by weight. In some embodiments, the preferred particle size of the elastomer depends upon the desired viscosity of the wound dressing formulation as well as the desired characteristics of quick drying, conformity, texture, and non-tackiness. In general, the particle size range can be from about 500 nm to about 100 μm. In some embodiments, the particle size ranges from about 1 to about 15 μm. The average particle size can be about 500 nm, about 1 μm, about 3 μm, about 5 μm, about 10 μm, about 15 μm, or greater.

[0020] The scar dressing formulation may optionally contain one or more additives. Additives include, but are not limited to therapeutic agents, antimicrobials (including antibacterials, antivirals and antifungals), stabilizers, thickeners, pigments, dyes, preservatives and antioxidants. In one embodiment, the scar dressing formulation contains from about 0.001% to about 25-35% by weight of at least one additive. In a particular embodiment, the additive is about 5% or less by weight, about 3% or less by weight, or about 1% or less by weight.

[0021] In some embodiments, the additive can increase the smoothness of the scar dressing formulation. Such additives include, but are not limited to glycerin, propylene glycol, butylene glycol, esters, diacyl glycerol esters, and starch.

[0022] In some scar dressing formulations, preservatives such as benzyl alcohol are useful. Carriers for therapeutic agents and/or antimicrobials such as water can also be employed.

[0023] Stabilizers specifically include amine stabilizers. Suitable thickeners are the swelling agents customarily used for gel formation in galenic pharmacy. Examples of suitable thickeners include natural organic thickeners, such as agar—agar, gelatin, gum arabic, a pectin, etc., modified organic natural compounds, such as carboxymethylcellulose or cellulose ethers, or fully synthetic organic thickeners, such as polyacrylic compounds, vinyl polymers, or polyethers.

[0024] The dressings of the presently described invention can be used to deliver a wide variety of compounds and agents. In a preferred embodiment, the compounds are agents that require a hydrophobic carrier or delivery vehicle. In another embodiment, the compounds for delivery are applied using single or multiple dosing regimens, such as daily, or multiple times each day. The presently described formulations are advantageous over other dressing formulations in that the prior art dressing can cause irritation after prolonged exposure. A typical example of such a formulation would be one comprising a retinoid or glycolic acid. Additionally, the presently described dressing formulations are contemplated for use in formulating chemical peels using glycolic acid or tricholoacetic acid.

[0025] Pharmacological agents include any bioactive agent including but not limited to antiseptics, antibacterial agents, antifungal agents or other adjuvants employed in burn and wound treatment. Such agents include organic molecules, preferably small organic compounds having a molecular weight of more than 50 and less than about 2,500 daltons; peptides, saccharides, fatty acids, steroids, purines, pyrimidines, derivatives, and structural analogs. Therapeutic agents also include peptide and protein agents, such as antibodies or binding fragments or mimetics thereof, e.g., Fv, F(ab′).sub.2 and Fab or growth factors, hormones and the like, particularly those that stimulate wound healing and skin growth. Analgesic agents and antibiotics such as phenylbutazone, oxyphenbutazone, indomethacin, naproxen, ibuprofen, acetaminophen, acetylsalicylic acid, penicillins, tetracyclines, and streptomycins are also suitable therapeutic agents useful in the wound dressing provided herein.

[0026] Among the agents particularly well suited for use with the presently described invention this include those agents that are unstable in water based systems including nitroglycerin, retinoic acid and its derivatives, vitamin D and its derivatives, acetyl salicylic acid, vitamin C, and some antibiotics, including tetracyclines, mupirocin, and cephalosporins.

[0027] Another distinct advantage of this drug delivery vehicle is its use with agents that are unstable in the presence of surfactants or where surfactants can cause damage to the drug over time, e.g. proteins, peptides and linked amino acids. The presently disclosed invention does not require the use of potentially harsh or denaturing surfactants, like sodium laural sulfate (SLS), sodium laureth sulfate (SLES), and ammonium laural sulfate (ALS), cocamidopropyl betaine, which are known to cause considerable irritation to those sensitive to them, it is ideal for formulation of drug products for patients with sensitive skin.

[0028] In formulations used to treat acne for example sensitive skin is very common and incorporating an anti-acne drug like benzoyl peroxide. One of the afflictions of psoriasis, in addition to the disfigurement of the disease itself, is tremendous skin sensitivity. Topically medications like corticosteroids, or calcipotriene are ideally incorporated into this non-irritating, easy to apply drug delivery vehicle. The term “corticosteroid” includes glucocorticoids as well as mineralocorticoids. Examples of corticosteroids include aclometasone dipropionate, amcinonide, betamethasone dipropionate, betamethasone sodium phosphate, betamethasone valerate, budesonide, clobetasol-17-propionate, clobetasone-17-butyrate, cortisone acetate, desonide, dexamethasone, dexamethasone sodium phosphate, fluocinolone acetonide, fluocinonide, fluocortolone, fluocortolone caproate, fluocortolone pivalate, fluprednidene acetate., halcinonide, hydrocortisone, hydrocortisone acetate, hydrocortisone-17-butyrate, hydrocortisone-17-valerate, methylprednisolone, mometasone, prednicarbate, prednisolone, prednisone, tixocortol pivalate, triamcinolone acetonide, and triamcinolone alcohol.

[0029] Drug categories in which this drug delivery vehicle can be use in are antihistamines, anti-infectives, anti-inflammatory agents including corticosteroids, anti-psoriatic agents, arnica, chloracetic acid, podofilox, and podophyllium resing, methionine, aluminum chloride hexahydrate, collagenase, hyaluronidase, ketatolytic agents, local anesthetics, minoxidil, psoralens, pigment agents including hydroquinone and monobenzone, 5-FU, retinoids, scabicides and pediculicides, wound healing agents, urea, dexpanthenol, Vitamin E, and sunscreens.

[0030] In a particular embodiment, the scar dressing formulation provided herein includes liposomes or liposomal compositions. Any suitable liposome or liposome composition may be employed. In some embodiments, the liposomes contain one or more therapeutic agents suitable for a wound dressing. Exemplary liposomes include those in U.S. Pat. Nos. 6,958,160 and 7,150,883. In one embodiment, the liposome comprises one or more lipids that is a diacylglycerol-PEG, particularly dioleolylglycerol-PEG-12.

[0031] The formulation is useful at any stage during scar evolution. The formulation can be applied to a wound that has completed the initial re-epithelization process or is a closed wound. The formulation is also useful to treat scars during the contraction, maturation or remodeling stages of wound healing. Thus, the scar can be less than about 1 week old, about 2 weeks old, about 1 month old, about 3 months old, or greater. Scars resulting from any type of wound may be treated in accordance with the present invention. Such scars include but are not limited to those resulting from or related to cuts, abrasions, traumatic skin injury, burns, and surgical wounds (such as those resulting from the use of a scalpel or a laser). Such scars can be atrophic, hypertrophic, keloid or contracture. The scar dressing formulation provided herein is particularly adapted for the treatment and/or prevention of hypertrophic scars of wounds following burn injuries.

[0032] In some embodiments, the scar dressing formulation is applied to the desired site while in a substantially flowable state. Once the scar dressing formulation is completely blended, it remains flowable and thus applicable to wound surfaces for up to 15 minutes. The flowable or substantially flowable state permits the wound dressing formulation to be custom fit to any contoured or shaped surface. Thus, the formulation is applied to the scar and can be worked with for about 2 minutes to about 15 minutes to cover the scar as necessary. After application, the scar dressing formulation is smoothed to a desired thickness and is substantially tack-free after mixing.

[0033] The scar dressing formulation typically forms a membrane having a thickness from about 0.1 mm to about 5 mm upon curing. The membrane can be continuous or substantially continuous over the surface of the scar. The continuous nature of the membrane allows the scar dressing to retain moisture in the scar as well as act as a bacterial barrier. The scar dressing is free or at least substantially free of air bubbles.

[0034] The scar dressing formulation can be transparent or substantially transparent. Transparency permits visual observation and monitoring of the scar as it continues to heal and improves the cosmetic appearance of the dressing (e.g., renders it less conspicuous).

[0035] The scar dressing formulation can remains on the scar for any time sufficient to permit healing of and/or resolution of the scar. In one embodiment, the scar dressing formulation forming a membrane remains on the wound at least about 1 day, at least about 2 days, at least about 4 days, at least about 6 days, or at least about 7 days to about 10 days.

[0036] After the scar dressing formulation has been on a scar for a time sufficient to promote and/or substantially complete healing and scar formation, the scar dressing can removed by gently wiping it from the scar. The healed wound is characterized by decreased redness, moistness, and minimal scarring.

[0037] Further provided herein is a kit comprising the components of the formulation as disclosed herein and optionally instructions for use.

[0038] A number of exemplary formulations are provided below.

[0039] Retinoic Acid

TABLE-US-00001 Dow corning 9040  83.5% Cyclomethicone 13.50% Propylene glycol  1.45% PEG-12 glyceryl dimyristate  0.05% Retinoic Acid  0.05% Benzyl Alcohol  1.00%

[0040] Glycolic Acid Peel

TABLE-US-00002 Dow corning 9040  60.5% Cyclomethicone 15.00% Glycerin  1.00% PEG-12 glyceryl dimyristate  1.5% Glycolic acid 20.00% Benzyl Alcohol  2.00%

[0041] Vitmain C

TABLE-US-00003 Volasil 725 80.5% Dow coming Powder 9506  7.0% Glycerin 1.00% PEG-12 glyceryl dimyristate 1.00% Vitamin C 9.50% Benzyl Alcohol 1.00%

[0042] Mupirocin

TABLE-US-00004 Volasil 725 79.5% Cyclomethicone 15.0% Glycerin 1.00% PEG-12 glyceryl dimyristate 1.00% Mupirocin  2.0% Benzyl Alcohol 1.50%

[0043] Somatostatin (Octreotide)

TABLE-US-00005 Dow corning 9040  85.5% Cyclomethicone 10.00% Glycerin  0.95% PEG-12 glyceryl dimyristate  1.5% Octreotide acetate  0.05% Benzyl Alcohol  2.00%

[0044] Clobetasol Proprionate

TABLE-US-00006 Dow corning 9040  85.5% Cyclomethicone 10.00% Propylene glycol  0.95% Ethanol  1.5% Clobetasol proprionate  0.05% Benzyl Alcohol  2.00%

[0045] Diphenhydramine

TABLE-US-00007 Volasil 725 80.5% Dow coming Powder 9506 13.5% Glycerin 1.00% PEG-12 glyceryl dimyristate 1.00% Diphenhydramine HCl 2.00% Benzyl Alcohol 2.00%

[0046] The following examples are offered to illustrate but not to limit the invention.

EXAMPLE 1

Scar Dressing Formulation Using Dimethicone Crosspolymers

[0047] KSG-210 is a dimethicone and dimethicone/PEG-10/15 crosspolymer that swells in silicone fluid. Minute cross-linked particles orient at the interface with fluid and to form a network. Botanisil S-19 is a silicone oil that is PEG-12 dimethicone.

[0048] GDM-12 is a specific type of self-forming, thermodynamically stable liposomes suitable for delivery of therapeutic agents (see U.S. Pat. No. 6,958,160). More specifically, GDM-12 is a mixture of liposomes formed from glycerol dimyristate (“GDM”) lipids where the head group of the lipid includes a polyethylene glycol (“PEG”) molecule with 12 C.sub.2H.sub.4O subunits in the PEG chain.

TABLE-US-00008 KSG-210  96.7500% 96.7500 Botanisil S-19  0.5000% 0.5000 GDM-12  0.5000% 0.5000 Benzyl Alcohol  0.7500% 0.7500 Purified Water  1.5000% 1.5000 Total: 100.0000% 100.0000

EXAMPLE #2

Scar Dressing Formulation Using Dimethicone Crosspolymers

[0049] Dow Corning® 9040 Silicone Elastomer Blend is a mixture of a high molecular weight silicone elastomer (i.e., dimethicone crosspolymer) in cyclomethicone (<1 wt %). It is a volatile diluent that is a silicon fluid. It has a viscosity range of 250,000-580,000 cp and a typical nonvolatile content of 12.0 wt % to 12.75 wt %. Cyclomethicone is a silicone oil.

TABLE-US-00009 1 Dow Corning 9040  83.5000% 83.5000 2 Cyclomethicone  15.0000% 15.0000 3 Glycerin  1.0000% 1.0000 4 GDM-12  0.5000% 0.5000 Total: 100.0000% 100.0000

EXAMPLE #3

Scar Dressing Formulation Using Dimethicone Crosspolymers

[0050] Volasil 7525 is a low viscosity mixture of the elastomers cyclohexasiloxane and cyclopentasiloxane. Dow Corning® 9506 powder is a silicone oil. More particularly, Dow Corning® 9506 is a dimethicone/vinyl dimethicone crosspolymer with a non-volatile content of 98% (minimum). It is a white free-flowing powder that provides dry smoothness and a powdery-light non-greasy skin feel. It also reduces tackiness.

TABLE-US-00010 1 Volasil 7525  85.5000% 85.5000 2 Dow Corning ® 9506 powder  13.0000% 13.0000 3 Glycerin  1.0000% 1.0000 4 GDM-12  0.5000% 0.5000 Total: 100.0000% 100.0000

[0051] While the invention has been explained in relation to its preferred embodiments, it is to be understood that various modifications thereof will become apparent to those skilled in the art upon reading the specification. Therefore, it is to be understood that the invention disclosed herein is intended to cover such modifications as fall within the scope of the appended claims.