Anti-itch scar management products, manufacturing processes thereof, and useful articles thereof

Abstract

The present invention relates to novel scar management products and methods for reducing skin scarring resulting from various types of skin injury and simultaneously reducing pruritus. In particular, the present invention relates to scar management products incorporating antipruritic agents that reduce and / or prevent skin scarring and pruritus, respectively.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 63 / 213,648, filed June 22, 2021, and incorporated herein by reference in its entirety.

[0002] The present invention relates to novel scar management products. In particular, the present invention relates to scar management products incorporating an antipruritic agent. The product is applied to the scarred area primarily to reduce and prevent scarring of the skin, and releases the antipruritic agent over time to reduce pruritus ("itch") during the scar maturation process. The present invention is similarly useful for reducing pruritus for conditions unrelated to scarring. [Background technology]

[0003] It is well known that silicone-based sheet and gel products are effective in preventing or reducing (together or individually "managing") skin scarring. Pruritus is a common symptom associated with wound healing and scar formation. This symptom is often particularly pronounced in large wounds such as burns and abrasions, but also in small wounds such as incisions and lacerations.

[0004] Numerous scar management products are available on the market. Bio Med Sciences, Inc., Allentown, Pennsylvania, manufactures and sells Oleeva® and Silon® brands of scar management products, including adhesive patches and dressings (for purposes of this specification, the terms patch and dressing may be used interchangeably). The inventor's U.S. Patent Nos. 4,832,009, 5,656,279, 5,980,923, and 7,087,135, which are incorporated herein by reference, describe wound dressings and scar management products that utilize interpenetrating polymer networks ("IPNs") of silicone and polytetrafluoroethylene. BioMed Science also manufactures and sells other scar management and skin care products under various brands and in various formats, including silicone-backed thermoplastic splints such as those described in the inventor's U.S. Patent No. 5,759,560, silicone-backed fabrics such as those described in the inventor's U.S. Patent No. 8,084,051, and silicone liquid and semi-solid silicone paste applicator sticks, both of which are incorporated herein by reference.

[0005] Many common antipruritic medications are available over the counter, including antihistamines such as diphenhydramine and hydroxyzine, which block the action of histamine, which causes itching. Corticosteroids such as hydrocortisone cream and other topical steroids are also commonly used. Steroids work by activating natural substances in the skin to reduce swelling, redness, and itching. Anti-irritants such as peppermint oil, menthol, or camphor, and local anesthetics such as lidocaine, pramoxine, or benzocaine are also used as antipruritic agents in topical creams or lotions.

[0006] Diphenhydramine, commonly known as Benadryl®, is of particular interest: it has a long history of safe and effective topical application for the temporary relief of itching caused by minor burns / cuts / scrapes, sunburn, insect bites, minor skin irritations, or rashes caused by poison ivy, poison oak, or poison sumac.

[0007] Biomed Science specifically contraindicates the use of creams or lotions under silicone scar sheeting products, as these types of substances can chemically degrade the silicone, thereby reducing the durability of the product. In the case of adhesive bandages and patches, creams and lotions can also stain the skin-contacting surface of the scar sheeting, affecting its adhesive properties and potentially negatively impacting its clinical usefulness.

[0008] The Franz cell chamber is an in vitro skin permeation assay frequently used in transdermal drug delivery system analysis. The apparatus consists of two primary chambers separated by a membrane, such as the Strat-M membrane from Millipore Sigma, Burlington, Massachusetts, USA. The test product is attached to the membrane via the upper chamber. The lower chamber contains a fluid from which samples are periodically taken for analysis to determine the release rate of the active pharmaceutical ingredient in the test product through the membrane. The chamber is typically maintained at a constant temperature of 37°C to mimic human clinical use. Summary of the Invention

[0009] In an effort to improve the art, the present inventors have created a scar management product that includes an antipruritic agent that reduces pruritus without compromising the adhesive and clinical properties of the scar patch. This is particularly useful because the use of a silicone scar product in combination with an antipruritic cream or lotion is problematic. The alternative of removing the scar management product and periodically applying a cream or lotion to achieve continued clinical benefit is even more problematic from a practicality and compliance standpoint. The present invention eliminates the problems of intermittent use of creams or lotions in combination with a silicone scar management patch while providing a long-term supply of an antipruritic agent for localized antipruritic benefit. [Brief description of the drawings]

[0010] [Figure 1] FIG. 1 shows a schematic diagram of a partial cross-section of a preferred scar management dressing constructed in accordance with the present invention, numeral 100 designating a monolithic design having an antipruritic agent uniformly dispersed in a silicone matrix 105 . [Diagram 2] FIG. 2 shows a dual layer design including a skin contacting surface 210 and an outer distal layer 220 . DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] In a preferred embodiment, the present invention comprises a bandage 100 having a silicone matrix 105 with an antipruritic agent uniformly dispersed throughout the silicone matrix 105, as shown in Figure 1. Bandage 100 has a skin-contacting surface 110 and an outer surface 120. In a preferred embodiment of the present invention shown in Figure 2, bandage 200 has a layer comprised of a silicone matrix 205 with an antipruritic agent uniformly dispersed throughout the silicone matrix 205. Bandage 200 has a skin-contacting surface 210, a distal non-skin-contacting backing layer 215, and an outer distal layer 220.

[0012] A scar management dressing of the present invention for preventing or reducing skin scarring and reducing pruritus comprises a skin contact layer having a skin contacting surface and an antipruritic agent uniformly dispersed throughout the skin contact layer.

[0013] Preferably, the skin contact layer of the bandage comprises a silicone-based material, such as a silicone, polydimethylsiloxane, polyorganosiloxane, silicone gel, or silicone elastomer. The bandage may also have an additional layer disposed over the skin contact layer, such as an interpenetrating polymer network ("IPN"), or a polymer that forms an interpenetrating polymer network ("IPN") with the skin contact layer, or an outer backing layer, such as a fabric, foam, nonwoven film, mesh, thermoplastic material, or material other than a fabric. The dressing may include Oleeva® Scar Management Dressing, Silon® Scar Management Dressing, or any of the dressings described in the present inventor's U.S. Pat. Nos. 4,832,009, 5,656,279, 5,980,923, 7,087,135, 5,759,560, and 8,084,051, all of which have an antipruritic agent uniformly dispersed throughout their skin-contacting layer.

[0014] Preferably, the antipruritic agent comprises one or more of diphenylhydramine HCl, corticosteroids, hydrocortisone, other topical steroids, diphenhydramine, anti-irritants (such as peppermint oil, menthol, or camphor), and local anesthetics (such as lidocaine, pramoxine, or benzocaine).

[0015] Preferably, the skin contact layer contains about 1% to about 20% by weight of the antipruritic agent, and more preferably, about 10% by weight of the antipruritic agent.

[0016] A number of methods can be used to manufacture the inventor's inventive scar management dressings for preventing or reducing scarring and reducing pruritus. Generally, during formation of the skin contact layer of the dressing, an antipruritic agent is dispersed throughout the material (e.g., a silicone-based material) that will form the skin contact layer of the dressing prior to formation of the skin contact layer. For example, a method of manufacturing the inventor's inventive scar management dressings for preventing or reducing skin scarring and reducing pruritus may include any of the methods described in the inventor's U.S. Pat. Nos. 4,832,009, 5,656,279, 5,980,923, 7,087,135, 5,759,560, and 8,084,051, except that the antipruritic agent is dispersed throughout the material (e.g., a silicone-based material) that forms the skin contact layer of the dressings disclosed in the inventor's U.S. Pat. Nos. 4,832,009, 5,656,279, 5,980,923, 7,087,135, 5,759,560, and 8,084,051 prior to formation of the skin contact layer.

[0017] In use, the scar management dressing of the present invention is placed over a patient's wound such that the skin contact layer contacts the wound to prevent or reduce skin scarring while simultaneously providing a long-term supply of antipruritic agent from the skin contact layer for a localized antipruritic effect. The following examples are not intended to be limiting. The following examples illustrate various preferred embodiments of the present invention.

[0018] Baseline: As a benchmark measurement for comparison with commercially available creams, Extra Strength Benadry® (2% diphenhydramine, Johnson & Johnson, New Brunswick, NJ) was applied to the surface of the artificial skin equivalent. The artificial skin equivalent includes a membrane (such as Millipore Sigma's Strat-M membrane) separating the two primary chambers of the Franz cell chamber in this baseline example and in Examples 1-4 below. The Franz cell chamber was used according to established methods with the following results:

[0019] Diphenhydramine 2% cream was applied to the artificial skin equivalents. TIFF2024523497000002.tif68170

[0020] Examples 1 to 4 Four Silon IPN films with a fabric backing layer were produced according to established methods, except that the antipruritic agent used in these Examples 1-4 was dispersed throughout the silicone phase of the IPN film. Two silicone formulations were used at two IPN coating thicknesses. The silicone was a polydimethylsiloxane, which in these Examples was a two-component addition-cured composition commercially available as a skin adhesive as Silpuran® 2130 and Silpuran® 2114 (Wacker Chemical Corp., Adrian, Michigan, USA).

[0021] Each of the four Silon IPN films (i.e., each of the test specimens) contained 10 wt % diphenhydramine (LGM Pharma, Erlanger, Kentucky, USA) in the silicone phase of the IPN. All were prepared under identical conditions as follows. TIFF2024523497000003.tif34170

[0022] Each specimen was tested in a Franz cell chamber using the artificial skin equivalent described above. The results for the baseline and the four example specimens are as follows: TIFF2024523497000004.tif51170

[0023] Additional examples illustrating the inventors' invention are as follows.

[0024] Example 5 A Silon IPN film with a fabric backing layer is manufactured according to established methods, except that the antipruritic agent used in this Example 5 is dispersed throughout the silicone phase of the IPN film. A two-component addition-cure silicone composition commercially available as MED-6350 (Avantor, Radnor, PA 19087) is used as the silicone phase of the IPN film and blended with diphenhydramine (LGM Pharma, Erlanger, Kentucky, USA) such that the silicone phase of the IPN film contains 10 wt% diphenhydramine, and the IPN film is cast at a thickness of 27 mils (686 microns).

[0025] Example 6 A Silon IPN film with a fabric backing layer is manufactured according to established methods, except that the antipruritic agent used in this Example 6 is dispersed throughout the silicone phase of the IPN film. A two-component addition cure silicone composition commercially available as MED-6350 (Avantor, Radnor, PA 19087) is used as the silicone phase of the IPN film and blended with diphenhydramine (LGM Pharma, Erlanger, Kentucky, USA) such that the silicone phase of the IPN film contains 1 wt% diphenhydramine, and the IPN film is cast at a thickness of 27 mils (686 microns).

[0026] Example 7 A Silon IPN film with a fabric backing layer is manufactured according to established methods, except that the antipruritic agent used in this Example 7 is dispersed throughout the silicone phase of the IPN film. A two-component addition-curable silicone composition commercially available as MED-6350 (Avantor, Radnor, PA 19087) is used as the silicone phase of the IPN film and blended with diphenhydramine (LGM Pharma, Erlanger, Kentucky, USA) such that the silicone phase of the IPN film contains 20% diphenhydramine by weight, and the IPN film is cast at a thickness of 27 mils (686 microns).

[0027] Example 8 A Silon IPN film with a fabric backing layer is manufactured according to established methods, except that the antipruritic agent used in this Example 8 is dispersed throughout the silicone phase of the IPN film. A two-component addition cure silicone composition commercially available as MED-6350 (Avantor, Radnor, PA 19087) is used as the silicone phase of the IPN film and blended with hydrocortisone (Sigma-Aldrich, Purchasable Chemical, St. Louis, MO, USA: 1317007 USP) such that the silicone phase of the IPN film contains 10% hydrocortisone by weight, and the IPN film is cast at a thickness of 27 mils (686 microns).

Claims

1. A scar management dressing for reducing and / or preventing skin scars and relieving pruritus, comprising: A skin contact layer comprising a silicone matrix sheet, wherein the skin contact layer has a skin contact surface, and the skin contact surface is provided with means for reducing and / or preventing skin scars; An antipruritic agent dispersed throughout the silicone matrix; and A scar management dressing comprising the above.

2. The scar management dressing according to claim 1, wherein the skin contact layer preferably contains 1% to 20% by weight of the antipruritic agent, more preferably 10% by weight of the antipruritic agent.

3. The scar management dressing according to any one of claims 1 to 2, wherein the silicone matrix comprises a silicone-based material including silicone, polydimethylsiloxane, polyorganosiloxane, silicone gel, or silicone elastomer.

4. The scar management dressing according to claim 1, wherein the antipruritic agent comprises diphenylhydramine HCl, corticosteroid, hydrocortisone, diphenhydramine, peppermint oil, menthol, camphor, lidocaine, pramoxine, and / or benzocaine.

5. The scar management dressing according to claim 1, wherein the antipruritic agent comprises a topical steroid, an anti-irritant, and / or a local anesthetic.

6. Further comprising the remaining part of the scar management dressing located on the skin contact layer, wherein the remaining part includes an interpenetrating polymer network, a polymer forming an interpenetrating polymer network together with the skin contact layer, a fabric, a foam, a non-woven film, a mesh, a thermoplastic material, and / or a material other than the fabric. The scar management dressing according to claim 1.

7. A method for manufacturing the scar management dressing according to claim 1, 2, 4, or 5, comprising: Mixing an antipruritic agent into a silicone formulation to form a mixture, wherein the silicone formulation includes polyorganosiloxane, silicone, silicone gel, silicone elastomer, or polydimethylsiloxane; Coating the mixture onto a carrier to form a layer of the mixture on the carrier; and Curing the layer of the mixture to form a skin contact layer comprising a silicone matrix sheet having the antipruritic agent dispersed throughout the silicone matrix. A method comprising the above steps.

8. The method according to claim 7, further comprising the step of applying expanded polytetrafluoroethylene to the layer of the mixture before curing.

9. The silicone formulation is silicone, the layer of the mixture and the expanded polytetrafluoroethylene form an interpenetrating polymer network of silicone and polytetrafluoroethylene, the interpenetrating polymer network has a first surface and a second surface, the first surface forms the skin contact surface of the skin contact layer, The method according to claim 8, further comprising the step of laminating a thermoplastic sub-material to the second surface of the interpenetrating polymer network.

10. The method according to claim 7, further comprising the step of applying an open mesh layer to the layer of the mixture before curing.

11. Before curing, applying a microporous polymer sheet membrane to the layer of the mixture so that the layer of the mixture can impregnate the microporous polymer sheet membrane or impregnating the layer of the mixture with the microporous polymer sheet membrane; and applying a backing material to the distal surface of the impregnated microporous polymer sheet material, the backing material contacting the mixture that has passed through the microporous polymer sheet membrane, The method according to claim 7, further comprising.

12. The method according to claim 11, wherein the backing material includes a fabric, a foam, a non-woven film, or a material other than a fabric.

13. Before curing, laminating a microporous polymer sheet membrane and a backing material to the layer of the mixture; and enabling the layer of the mixture to impregnate the microporous polymer sheet membrane or impregnating the layer of the mixture with the microporous polymer sheet membrane, The method according to claim 7, further comprising.

14. The method according to claim 13, wherein the backing material includes a fabric, a foam, a non-woven film, or a material other than a fabric.

15. The carrier includes a fabric, and the method includes the step of making a scar management bandage from the fabric coated with the mixture The method according to claim 7, further comprising.

16. The method according to claim 15, wherein the scar management bandage is a garment. **Claim 17**: The silicone matrix includes a silicone-based material containing silicone, polydimethylsiloxane, polyorganosiloxane, silicone gel, or silicone elastomer, and the antipruritic agent includes diphenylhydramine HCl, corticosteroid, hydrocortisone, diphenhydramine, peppermint oil, menthol, camphor, lidocaine, pramoxine, and / or benzocaine. The scar management dressing according to claim 2.

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