Removable film-forming gel compositions featuring adhesion promoters

Abstract

To provide film-forming gel compositions useful in creating conformable and flexible gel bandages.SOLUTION: A gel composition for use as a conformable film bandage comprises: a silicone containing, film-forming polymer; an amine-rich adhesion promoter; a volatile solvent; and an active ingredient. A film cast from the gel composition is self-supporting on a biological substrate and can be peeled off the substrate.SELECTED DRAWING: None

Description

Technical Field

[0001] Related Applications This patent application claims priority to U.S. Provisional Patent Application No. 62 / 855,350, filed May 31, 2019, and is related to International Application PCT / US2016 / 025904, International Application PCT / US2016 / 025910, and International Application PCT / US2017 / 055454, each titled "Removable Film-forming Gel Compositions and Methods for Their Application," the entire disclosures of which are incorporated herein by reference in their entirety.

Summary of the Invention

[0002] The present disclosure provides a gel composition that is easy to apply and dries to form a durable film bandage and other tissue protectants. The film-forming gel composition of the present disclosure is flexible, breathable, water-resistant, non-irritating, skin-friendly, and can be easily removed by peeling or other forces exerted by the wearer. The gel composition has improved cohesiveness and integrity when dried. Optionally, the gel composition is capable of absorbing moisture and wound exudate, particularly blood. Thus, the film-forming composition is particularly well-suited for use as a liquid bandage or skin protectant. The gel composition is useful for protecting or treating skin, tissue, organs, nails, hydrated tissues, and mucous membranes, such as hemorrhagic injuries, surgical sites, skin ulcers, herpes, cuts, rashes, abrasions, incisions, and blisters, abraded gums and other oral surfaces, hemorrhoids and abraded body areas, and other mucous membrane incisions and wounds.

[0003] In certain advantageous embodiments, neither this gel composition nor the later-formed film irritates the skin and other tissues during application, drying, or use after drying. The resulting bandage is desirably substantially painless while worn and can be easily removed by peeling, optionally with substantially no pain or disruption at the wound site. The formed dry bandage can exhibit high water vapor permeability throughout. This gel composition can form a tough, slightly adhesive film that can absorb and retain large amounts of exudate in certain situations when applied to a surface moistened by blood or body fluid.

[0004] In particular, the gel compositions of the present disclosure can dry in a single application to form a relatively thick, flexible film having desired wound healing properties (e.g., breathability, flexibility, non-stinging). In particular, the gel composition can be applied to the skin at a coating thickness of 50 to 120 mils (about 1.27 to about 3.048 mm) at room temperature, and the adhesive film can be formed to have a thickness of at least 2 mils (about 0.0508 mm), at least 3 mils (about 0.0762 mm), at least 4 mils (about 0.1016 mm), at least 5 mils (about 0.127 mm), or at least 6 mils (about 0.1524 mm). Once dried on the skin, this gel composition can have a 180-degree peel adhesion from human skin in a skin adhesion test of 900 g or less per square inch (about 2.54 square cm) and a keratin removal level of 40% or less in a skin removal test. Thus, the dried film can be removed by the application of force without substantial damage to the underlying skin or wound site.

[0005] In one aspect, this gel composition comprises a film-forming polymer, a compatible tackifier, a disinfectant, a volatile solvent, and optionally at least one of a cationic polymer acting as a coagulant and an amine-rich adhesion promoter. At least the film-forming polymer and the tackifier are typically soluble in the solvent. This gel composition may be silicone-based in that the film-forming material comprises a silicone-containing polymer. The film-forming polymer may be composed of a segmented siloxane copolymer including silicone polyurea block copolymers and polydiorganosiloxane polyoxamide block copolymers. These polymeric materials are typically non-adhesive materials having release properties in many cases and can be formulated with a silicate tackifying resin (e.g., MQ resin), an amine-rich adhesion promoter, or certain coagulants. A particularly suitable film-forming polymer is polydiorganosiloxane polyoxamide.

[0006] In one aspect, the present disclosure provides a film-forming gel composition for use as a conformable film dressing, the composition comprising a silicone-containing film-forming polymer; an amine-rich adhesion promoter, and a volatile solvent. A film cast from this composition is self-supporting on a biological substrate and can be peeled from the substrate without substantially compromising the integrity of the film such that at least a portion of the film is removable in a single continuous layer.

[0007] In yet another aspect, the present disclosure provides a film useful as a conformable dressing, the film exhibiting an upright MVTR of at least 300 g / m 2 / 24 hours, skin adhesion of at least 50 g / inch (about 2.54 cm) and 900 g / inch (about 2.54 cm) or less, elongation of at least 100%, and a maximum tensile strength of at least 0.3 MPa. At least a portion of the film has a thickness of at least 2 mils (about 0.0508 mm) and 20 mils (about 0.508 mm) or less, the film is self-supporting, and consists of a single layer.

[0008] This film may comprise, based on the weight of the film: (a) 50 to 75 wt% of a film-forming polymer, (b) 0.1 to 30 wt% of a filler, and (c) 10 to 60 wt% of an amine-rich adhesion promoter.

[0009] The terms "comprises", "comprising", and variations thereof do not have a limiting meaning when they appear in the detailed description and claims.

[0010] The terms "preferred" and "preferably" refer to embodiments of the invention that can provide certain benefits under certain circumstances. However, other embodiments may also be preferred under the same or other circumstances. Further, the listing of one or more preferred embodiments does not imply that other embodiments are not useful, nor is it intended to exclude other embodiments from the scope of the invention.

[0011] When recited herein, all numbers should be assumed to be modified by the term "about" unless otherwise indicated.

[0012] As used herein, the terms "a", "an", "the", "at least one", and "one or more" are used interchangeably. Thus, for example, a composition comprising "a" cationic antimicrobial agent can be interpreted as a gel composition comprising "one or more" cationic antimicrobial agents.

[0013] Also herein, the recitation of numerical ranges by endpoints includes all numbers subsumed within that range (e.g., 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, 5, etc.).

[0014] When used herein as a modifier to a feature or attribute, the term "generally" means that, unless otherwise specifically defined, the feature or attribute can be readily recognized by one of ordinary skill in the art, but does not require absolute precision or complete conformity (e.g., for a quantifiable feature, within + / - 20%). The term "substantially" means, unless otherwise specifically defined, a high degree of approximation (e.g., for a quantifiable feature, within + / - 10%), but also does not require absolute precision or complete conformity. Terms such as the same, equal, uniform, constant, exact, and homogeneous are understood to be within the range of normal tolerances or measurement errors applicable to a particular situation rather than requiring absolute precision or complete conformity.

[0015] The term "polydiorganosiloxane" refers to the formula

Chemical formula

[0016] As used herein, "film-forming" refers to a composition that forms a continuous layer that does not peel off after simple bending of the tissue when the composition is dried on the skin or mucosal tissue under ambient conditions (e.g., 23 °C (about 296.15 K) and 50% relative humidity (RH)).

[0017] As used herein, "moisture vapor transmission rate" (MVTR), also referred to as "water vapor transmission rate" (WVTR), is a measure of the passage of water vapor through a substance.

[0018] As used herein, "ready-to-use" refers to a composition intended to be applied (e.g., to skin or mucosal tissue) without dilution. It should be understood that the amounts of all specified ingredients listed (unless otherwise specified) are for the "ready-to-use" gel composition.

[0019] As used herein, "effective killing" means rendering a microorganism (e.g., bacteria and fungi) ineffective by killing or otherwise inactivating (e.g., a virus), and can be distinguished from disrupting microbial adhesion or mere bacteriostasis. Typically, effective killing results in at least a 0.5 log reduction using the antibacterial effect test described herein, desirably at least a 1 log reduction, more preferably at least a 2 log reduction, and even more preferably at least a 3 log reduction. In the compositions described herein, the concentration or amount of a component, when considered separately, may not kill to an acceptable level, or may not kill an undesirable microorganism over a very broad spectrum, or may not kill very rapidly; however, when used together, it should be understood that such components confer improved (preferably synergistic) antibacterial activity (compared to the same component used alone under the same conditions).

[0020] In yet another aspect, the present disclosure provides a gel composition and a film comprising an active ingredient, e.g., a drug.

[0021] The above summary of the present disclosure is not intended to describe each disclosed embodiment or every implementation of the present invention. The following detailed description illustrates exemplary embodiments in more detail. Throughout this application, guidance is provided through lists of examples, which may be used in various combinations. In each case, the listed descriptions serve only as representative groups and should not be construed as an exhaustive list. BRIEF DESCRIPTION OF THE DRAWINGS

[0022]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

DETAILED DESCRIPTION OF THE INVENTION

[0023] The figures identified above describe some embodiments of the present disclosure, but as described in the detailed description, other embodiments are also contemplated. In all cases, the present disclosure presents the invention by way of example and not limitation. It should be understood that numerous other changes and embodiments may be devised by those skilled in the art within the scope and spirit of the principles of the present invention.

[0024] The present disclosure provides a wide variety of flexible, breathable, non-irritating, skin-friendly, self-supporting film-forming compositions. Gel compositions used to form bandages or other protective agents typically include a silicone-containing film-forming polymer, a tackifier, a coagulant, a disinfectant, and a volatile solvent. Other compositions may not include a disinfectant, a coagulant, or both. The gel compositions of the present disclosure may include fillers, antibiotics, surfactants, and other additives (e.g., release agents for areas of the underlying tissue being covered) to improve the comfort or treatment of the user. A specific feature of the present disclosure is that the gel material can act at room temperature (20 °C) when applied to the user's tissue and form a film in less than a few minutes. This film can be conformable, comfortable, elastic, and flexible. This film does not significantly irritate the skin and mucous membranes when placed during application and during use after drying. The dried film is substantially painless and can be removed without substantial pain. The formed dried bandage is substantially non-water-sensitive and has a high water vapor permeability throughout. The bandage can be formed when applied to a surface moistened with water, blood, or body fluid and can be formed in a reasonable variation thereof in a short time at standard room temperature. The use of the gel composition over certain bleeding or exudative wounds provides a distinct advantage over previously available compositions that rely on maintaining a dry or drier target surface. The compositions of the present disclosure also tend to be more coatable in relatively thicker applications, which is easier for the user to see and, as a result, easier to remove. The combination of features enables the compositions of the present disclosure to cover and protect a wide variety of open wounds. Protective wounds include, but are not limited to, abrasions, lacerations, scratches, punctures, burns, and pressure sores.

[0025] Certain gel compositions of the present disclosure, particularly disinfectant compositions, have the following characteristics: relatively high levels of sterilization when an antibacterial agent is present (or when the composition is essentially antibacterial); relatively short drying times; generally clear visibility of underlying tissue; good adhesion to the skin when dry; little or no tackiness when dry; the ability to release an active agent, such as an antibacterial agent or a coagulant; and include one or more of the foregoing, and are a single continuous film, preferably removable relatively easily without the need for an organic solvent-based remover or other dissolution.

[0026] In other embodiments, the gel composition can be used to secure medical articles to the skin or other tissue. Useful medical articles that can be secured by the dried film obtained from such a gel composition include, but are not limited to: nasogastric tubes, blood flow catheters, dialysis catheters and tube stents, surgical instruments, tympanostomy tubes, shunts including shunts for hydrocephalus, postoperative drainage tubes and drainage devices, urinary catheters, endotracheal tubes, other implantable devices, and other indwelling devices.

[0027] The drying time of the film of the present disclosure is preferably about 5 minutes or less, more preferably about 3 minutes or less, even more preferably about 2 minutes or less, and most preferably about 1.5 minutes or less on the skin when measured at 23°C at a relative humidity of 45 - 55%. The drying time can be considered the shortest time for the composition applied at a specified coating weight to visually dry and demonstrate no transfer of the composition to a gloved hand covering it, with the tackiness at a minimum level. The drying time of a given composition can be measured under ASTM D 5895-13, particularly by a circular time drying recorder (test method B). The drying time measured under this method may be longer than that experienced on the skin. It should be noted that the composition may have no tackiness (no transfer of the composition to a gloved hand) and still not be completely dry. Thus, the time with no tackiness is preferably about 2 minutes or less, about 1 minute or less, and in some embodiments, about 30 seconds or less.

[0028] The desired specific viscosity of the gel composition depends in part on the intended application. For example, if the application is to a particular location on the skin (e.g., the surface of the elbow, the surface of the knee, and the like), a higher viscosity composition is preferred to prevent the composition from "running" to unintended locations. The preferred compositions of the present disclosure also have a viscosity such that, in the present situation, the applied gel does not run during drying and forms a relatively thick film while still readily conforming to tissue. In a conforming film, the viscosity of the gel composition is at least 20,000 centipoise (cps) (about 20 Pa·s), at least 50,000 cps (about 50 Pa·s), at least 60,000 cps (about 60 Pa·s), and in other embodiments at least 70,000 cps (about 70 Pa·s). To avoid undue difficulty in applying the gel composition to the target area, the viscosity, when measured at 23 °C using a Brookfield LVT viscometer and the procedure described in the Examples section, is about 1,100,000 cps (about 1,100 Pa·s) or less, about 800,000 cps (about 800 Pa·s) or less, about 600,000 cps (about 600 Pa·s) or less, about 400,000 cps (about 400 Pa·s) or less, and in other embodiments, about 250,000 cps (about 250 Pa·s) or less. This viscosity range allows the composition to be applied to the skin as a uniform film that will surely and rapidly dry to maintain structural integrity through wear in certain situations. Further, certain compositions may benefit from a higher viscosity when applied in that (in combination with other variables) a higher viscosity composition may exhibit less precipitation (i.e., less precipitation of components from a composition that would otherwise be dissolved or dispersed). Applicants have found that certain gel compositions having a specific viscosity in the range of 200,000 cps (about 200 Pa·s) to 500,000 cps (about 500 Pa·s) (particularly 250,000 cps (about 250 Pa·s) to 400,000 cps (about 400 Pa·s)) still result in a protective coating film exhibiting the characteristics and benefits described below while being more easily applied, positioned, and dried.

[0029] The dried films of the compositions of the present disclosure are generally flexible and durable and are relatively lightly adhesive. That is, they do not crack or peel off like brittle films, stay on the skin without requiring debris for removal. Significantly, the film-forming polymers and compatible tackifiers contribute to achieving a delicate balance among low tack, breathability, and flexibility. The compositions are thus useful in surface areas that are exposed to high levels of movement, such as knuckles, knees, elbows, feet, and the like. The films of the dried gel compositions can have a thickness of at least 1 mil (about 0.0254 mm), at least 1.5 mils (about 0.0381 mm), at least 2 mils (about 0.0508 mm), at least 4 mils (about 0.1016 mm), or at least 8 mils (about 0.2032 mm), typically 25 mils or less (about 0.635 mm), 20 mils (about 0.508 mm) or less, 15 mils (about 0.381 mm) or less, or 10 mils (about 0.254 mm) or less. As used herein, the term "mil" refers to 0.001 inch (about 2.54×10 -2 mm), and 1 mil (about 0.0254 mm) is equal to about 0.0025 centimeter or about 0.025 millimeter or about 25 micrometers. The gel compositions of the present disclosure can be coated in a manner that forms a film having a uniform or substantially uniform thickness, but for example, variations in the pressure applied or the applicator used can result in a thickness that varies through the film layer. In presently preferred embodiments, the thickness of the film on the target (e.g., wound or skin lesion) is at least 2 mils (about 0.0508 mm) thick, but the area of the film surrounding the target (e.g., uninjured tissue) can exhibit a relatively thinner film thickness. Certain application methods, including those described below, can help to impart a more uniform thickness to normalize the drying time and improve protection.

[0030] The compliance and durability characteristics of the dried film can be determined in part by standard tensile and elongation tests. The elongation of the dried film can range from 50%, 75%, or 100% to 1400%. In some embodiments, the elongation is at least 100% and 600% or less. The maximum tensile strength is typically at least 0.2 MPa, at least 0.3 MPa, or at least 0.4 MPa, and is typically 2 MPa or less. In some embodiments, the maximum tensile strength is 2 MPa or less, 1.5 MPa or less, or 1 MPa or less. The Young's modulus is typically at least 0.5 MPa, at least 0.6 MPa, at least 0.7 MPa, at least 0.8 MPa, at least 0.9 MPa, or at least 1 MPa, and is typically about 2 MPa or less. In some embodiments, the Young's modulus of the tested film is at least 0.7 MPa and typically 1.5 MPa or less. Such tensile and elongation characteristics can be measured, for example, by the methods outlined in ASTM D882-12.

[0031] The dried films of the compositions of the present disclosure are also relatively lightly adhesive. Suitable films typically have a peel adhesion to skin by the skin adhesion test described below of at least 25 g / inch (about 2.54 cm), in some embodiments at least 50 g / inch (about 2.54 cm), and in some embodiments at least 75 g / inch (about 2.54 cm). Suitable dried films typically have a peel adhesion by the skin adhesion test of 1000 g / inch (about 2.54 cm) or less, in some embodiments 900 g / inch (about 2.54 cm) or less, and in some embodiments 600 g / inch (about 2.54 cm) or less. The relatively lightly adhesive films within the above ranges can typically remain in place on the surface to which they are applied during the desired period of wear and, advantageously, without causing tearing or ripping of the surface: on a living surface, such as skin, without removing a portion of the epidermis or damaging the skin, scar, or tissue under the film, and can also be removed (e.g., by the force applied by the user). This can be a significant advantage over prior art silicone-containing liquid bandages (see, e.g., U.S. Patent No. 8,197,803 (Salamone et al.)) that often rely on normal desquamation at the application site for proper removal.

[0032] Dried films cast from the gel compositions of the present disclosure can exhibit a water vapor transmission rate of at least 300 g / m 2 / 24 hours, thus contributing to both preventing dehydration of the wound area and promoting moist wound healing. As used herein, the dry MVTR (or upright MVTR) of a dried film bandage is measured by ASTM E-96-80 at 40 °C and 20% relative humidity using the upright cup method. The wet MVTR (or inverted MVTR) is measured by the same method except that the water is in direct contact with the test sample by inverting the sample bottle.

[0033] Factors affecting the MVTR of the dried film from the gel composition of the present invention include, but are not limited to, the thickness of the film layer on the tissue, the relative amount of solids in the gel composition before application, the formulation of the gel composition, the viscosity of the gel composition, and the coating structure of the gel (i.e., continuous film or pattern). The dried film cast from the gel composition of the present disclosure has a dry MVTR of at least 300 g / m 2 / 24 h, more preferably at least 500 g / m 2 / 24 h, even more preferably at least 1000 g / m 2 / 24 h, even more preferably at least 1500 g / m 2 / 24 h. The dried film preferably has a wet MVTR of at least 500 g / m 2 / 24 h, more preferably at least 900 g / m 2 / 24 h, even more preferably at least 1000 g / m 2 / 24 h, even more preferably at least 1300 g / m 2 / 24 h. Different film regions may contain different dry and / or wet MVTR values.

[0034] Surprisingly, the gel composition exhibits the improved MVTR even when applied at a greater coating weight having a higher percent solids (and resulting in a greater film thickness) than typical liquid bandages. In part due to this breathability and other components, the dried film of the present composition can improve wound healing by increasing the rate of re-epithelialization of the wound. The disclosed gel composition can be applied in liquid form using a brush, rod, finger, sponge, fabric, dropper, etc.; in spray or mist form; or by any other applicable technique for applying liquid to a surface, such as wiping fibers, cotton swabs, or solid paddle applicators, to the skin, mucous membranes, etc. In certain advantageous embodiments, the composition is applied at a wet coating thickness between 25 mils (about 0.635 mm) and 150 mils (about 3.81 mm), and in certain embodiments, between 40 mils (about 1.016 mm) and 100 mils (about 2.54 mm). Typically, after drying, the resulting film preferably has a thickness of about 2 to about 20 mils (about 0.0508 to about 0.508 mm). Relatively thicker films can be advantageous with respect to site protection and ease of removal, but typically require a longer drying time than relatively thinner films of the same composition. Overall, in one embodiment, the total solids of the gel composition is at least 15 wt% of the total gel composition, in one embodiment, at least 20 wt%, and in one embodiment, less than 35 wt%.

[0035] Advantageously, the dried film of the present disclosure is self-supporting after a single application of the gel composition. As used herein, a "self-supporting" film exhibits a desirable combination of breathability, durability, and flexibility in a single layer without the application of an additional layer of the gel composition on the outer surface of the dried film. Further, a "self-supporting" film does not require an additional flexible backing for continuous wear (i.e., continuous presence on the skin or other target tissue for at least 8 hours). One presently desirable film has at least 300 g / m 2Exhibit 24-hour upright MVTR, film thickness of at least 2 mils (about 0.0508 mm) and 20 mils or less (about 0.508 mm), skin adhesion of 900 g / inch (about 2.54 cm) or less, elongation of at least 100%, and maximum tensile strength of at least 0.4 MPa.

[0036] Typical gel compositions may contain, based on the total weight of the gel composition, (a) 10 - 15 wt% film-forming polymer, (b) 3 - 5 wt% tackifier, (c) 0 - 0.3 wt% disinfectant, (d) 0 - 3 wt% filler, (e) 60 - 80 wt% solvent, (f) 0 - 5 wt% cationic polymer, and optionally (g) 0.1 - 2 wt% silicone surfactant.

[0037] The dried films of the present disclosure typically contain, based on the total weight of the dried film, (a) 50 - 75 wt% film-forming polymer, (b) 15 - 30 wt% tackifier, (c) 0.1 - 0.5 wt% disinfectant, (d) 0 - 12 wt% filler, (e) 0 - 20 wt% cationic polymer, and optionally (f) 0.5 - 15 wt% silicone surfactant.

[0038] Film-forming polymer In one aspect, the gel compositions of the present disclosure contain a film-forming polymer capable of forming a substantially continuous layer upon drying. Suitable film-forming polymers are at least partially soluble in volatile solvents and include silicone-containing polymers. Particularly suitable silicone-containing polymers include polysiloxane polyamide, silicone polyurea, and silicone polyamine.

[0039] The film-forming polymer is typically soluble in the solvent system used in the gel composition. As used herein, a polymer is "soluble" or "solubilized" when the amount of the polymer present in the solvent system is completely dissolved in the solvent system without the polymer precipitating in solution or forming visibly swollen gel particles. As used herein, the term "solubility limit" is the maximum amount of a given polymer that can be dissolved in a given solvent system, measured as a percentage of the total weight of the solution. For example, the film-forming polymer can have a solubility limit of at least 5 wt%, at least 10 wt%, at least 15 wt%, at least 20 wt% in hexamethyldisiloxane (HMDS), isooctane, or any other solvent system described herein, based on the total weight of the gel composition.

[0040] The silicone-containing polymers useful in practicing the present disclosure can have an intrinsic viscosity ("IV") of at least 0.9, at least 1.45, at least 1.68, or at least 1.8. The silicone-containing polymers typically have an intrinsic viscosity of less than 3 because polymers having an intrinsic viscosity greater than 3 can be difficult to solubilize in certain situations. Polymers with lower IVs, among other things, have higher solubility in solvents and solvent systems, so while they can be film formers, they may dry more slowly and remain tacky after application. The IV of the polymer can be controlled by varying the initiator, initiator concentration, reaction temperature, reaction solvent, reaction method, and other parameters known to those skilled in the art.

[0041] Siloxanes and polysiloxane polyamides Siloxane polymers have unique properties that mainly stem from the physical and chemical characteristics of the siloxane bond. These properties include a low glass transition temperature, thermal and oxidative stability, UV resistance, low surface energy, and hydrophobicity. However, siloxane polymers often lack tensile strength in many cases. The low tensile strength of siloxane polymers can be improved by forming block copolymers. Some block copolymers contain either "soft" siloxane polymer-like blocks or segments and various "hard" blocks or segments. Particularly suitable elastomeric siloxane-based elastomeric polymers are the segmented polymers of the following formulas I and II.

[0042] In some embodiments, the silicone-containing polymer is a linear polydiorganosiloxane, a linear polydiorganosiloxane polyamide block copolymer, or a polydiorganosiloxane urethane-containing copolymer, although other silicone-containing polymers may also be useful.

[0043] Polydiorganosiloxanes can have various organic substituents on the silicon-carbon atoms of the polysiloxane. For example, each organic substituent can independently be alkyl, haloalkyl, arylalkenyl, alkylarylenyl, alkenyl, aryl, or aryl substituted by alkyl, alkoxy, or halo. Polydiorganosiloxanes have repeating units of the general formula (Si(R 7 )2O -) (wherein R 7 is as defined below for any of the embodiments of R 7 ). Examples include dimethyl silicone, diethyl silicone, and diphenyl silicone. In some embodiments, at least 40 percent, in some embodiments, R 7At least 50 percent, at least 60 percent, at least 70 percent, at least 80 percent, at least 90 percent, at least 95 percent, at least 98 percent, or at least 99 percent of the groups can be phenyl, methyl, or combinations thereof. In some embodiments, R 7 At least 40 percent, at least 50 percent, at least 60 percent, at least 70 percent, at least 80 percent, at least 90 percent, at least 95 percent, at least 98 percent, or at least 99 percent of the groups are methyl. High molecular weight polydimethylsiloxane (PDMS) is commercially available, for example, from Dow Corning Corporation, Midland, MI.

[0044] The linear polydiorganosiloxane polyamide block copolymers useful in practicing the present disclosure contain at least two repeating units of Formula I. [Chemical formula] In this formula, each R 7 is independently alkyl, haloalkyl, arylalkenylenyl, alkylarylenylenyl, alkenyl, aryl, or aryl substituted by alkyl, alkoxy, or halo. Each Y is independently alkylene, arylalkylene, alkylarylene, or combinations thereof. Subscript n is independently in the range of 0 to 1500, and subscript p is in the range of 1 to 10. Each group B is independently a covalent bond, alkylene, arylalkylene, alkylarylene, arylene, or combinations thereof. When each group B is a covalent bond, the polydiorganosiloxane polyamide block copolymer of Formula I is referred to as a polydiorganosiloxane polyoxamide block copolymer. Group G is a divalent group equal to the residue unit obtained by subtracting two -NHR 8 HN - G - NHR 8 groups from a diamine of the formula. Group R 8 8 ​is hydrogen or alkyl (e.g., alkyl having 1 to 10 carbon atoms, 1 to 6 carbon atoms, or 1 to 4 carbon atoms); or R taken together with G and the nitrogen to which both are attached. 8 form a heterocyclic group. * ) indicates the point of attachment of the repeat unit to another group in the copolymer, such as another repeat unit of Formula I.

[0045] R in Formula I 7 Suitable alkyl groups for typically have 1 to 10 carbon atoms, 1 to 6 carbon atoms, or 1 to 4 carbon atoms. Examples of useful alkyl groups include methyl, ethyl, isopropyl, n-propyl, n-butyl, and iso-butyl. 7 Haloalkyl groups suitable for R are often those in which only a portion of the hydrogen atoms of the corresponding alkyl group are replaced by halogen. Examples of haloalkyl groups include chloroalkyl and fluoroalkyl groups having 1 to 3 halo atoms and 3 to 10 carbon atoms. 7 Alkenyl groups suitable for R often have 2 to 10 carbon atoms. Exemplary alkenyl groups often have 2 to 8 carbon atoms, 2 to 6 carbon atoms, or 2 to 4 carbon atoms, such as ethenyl, n-propenyl, and n-butenyl. 7 Suitable alkenyl groups for often have 6 to 12 carbon atoms. Phenyl is an example of an aryl group. The aryl group may be unsubstituted or substituted with alkyl (i.e., alkylarylenyl group) (wherein the alkyl group may be, for example, an alkyl having 1 to 10 carbon atoms, 1 to 6 carbon atoms, or 1 to 4 carbon atoms), alkoxy (e.g., alkoxy having 1 to 10 carbon atoms, 1 to 6 carbon atoms, or 1 to 4 carbon atoms), or halo (e.g., chloro, bromo, or fluoro). R 7Arylalkylenyl and alkylarylenyl groups suitable for usually have an alkylene group having 1 to 10 carbon atoms and an aryl group having 6 to 12 carbon atoms. In some arylalkylenyl and alkylarylenyl groups, the aryl group is phenyl and the alkylene group has 1 to 10 carbon atoms, 1 to 6 carbon atoms, or 1 to 4 carbon atoms. For example, R 7 may be an arylalkylenyl group, and any of these alkylene groups is bonded to a phenyl group.

[0046] In some embodiments, in some repeating units of formula I, R 7 at least 40 percent of the groups, in some embodiments at least 50 percent, are phenyl, methyl, or a combination thereof. For example, at least 60 percent, at least 70 percent, at least 80 percent, at least 90 percent, at least 95 percent, at least 98 percent, or at least 99 percent of the R 7 groups can be phenyl, methyl, or a combination thereof. In some embodiments, in some repeating units of formula I, at least 40 percent of the R 7 groups, in some embodiments at least 50 percent, are methyl. For example, at least 60 percent, at least 70 percent, at least 80 percent, at least 90 percent, at least 95 percent, at least 98 percent, or at least 99 percent of the R 7 groups can be methyl. The remaining R 7 groups can be selected from alkyl having at least 2 carbon atoms, haloalkyl, arylalkylenyl, alkylarylenyl, alkenyl, aryl, or aryl substituted by alkyl, alkoxy, or halo.

[0047] In Formula I, each Y is independently an alkylene, arylalkylene, alkylarylene, or a combination thereof. Suitable alkylene groups typically have up to 10 carbon atoms, up to 8 carbon atoms, up to 6 carbon atoms, or up to 4 carbon atoms. Examples of alkylene groups include methylene, ethylene, propylene, butylene, and the like. Suitable arylalkylene and alkylarylene groups typically have an arylene group having 6 to 12 carbon atoms bonded to an alkylene group having 1 to 10 carbon atoms. In some arylalkylene and alkylarylene groups, the arylene moiety is phenylene. That is, a divalent arylalkylene or alkylarylene group has phenylene bonded to an alkylene having 1 to 10 carbon atoms, 1 to 8 carbon atoms, 1 to 6 carbon atoms, or 1 to 4 carbon atoms. When referring to group Y, as used herein, "a combination thereof" refers to a combination of two or more groups selected from alkylene and arylalkylene or alkylarylene groups. The combination can be, for example, a single alkylarylene bonded to a single alkylene (e.g., alkylene-arylene-alkylene). In one example of an alkylene-arylene-alkylene combination, the arylene is phenylene and each alkylene has 1 to 10 carbon atoms, 1 to 6 carbon atoms, or 1 to 4 carbon atoms.

[0048] In Formula I, each subscript n is independently in the range of 0 to 1500. For example, the subscript n can be up to 1000, up to 500, up to 400, up to 300, up to 200, up to 100, up to 80, up to 60, up to 40, up to 20, or up to 10. The value of n is often at least 1, at least 2, at least 3, at least 5, at least 10, at least 20, or at least 40. For example, the subscript n can be in the range of 40 to 1500, 0 to 1000, 40 to 1000, 0 to 500, 1 to 500, 40 to 500, 1 to 400, 1 to 300, 1 to 200, 1 to 100, 1 to 80, 1 to 40, or 1 to 20.

[0049] The subscript p ranges from 1 to 10. For example, the value of p is, in many cases, an integer with a maximum of 9, a maximum of 8, a maximum of 7, a maximum of 6, a maximum of 5, a maximum of 4, a maximum of 3, or a maximum of 2. The value of p can range from 1 to 8, from 1 to 6, or from 1 to 4.

[0050] In formula I, the group G is of the formula R 8 HN-G-NHR 8 is a residual unit equal to that obtained by removing two amino groups (i.e., -NHR 8 groups) from the diamine compound. The diamine may have a primary or secondary amino group. The group R 8 is hydrogen or alkyl (e.g., alkyl having 1 to 10 carbon atoms, 1 to 6 carbon atoms, or 1 to 4 carbon atoms), or R 8 together with the nitrogen to which both G and R are attached forms a heterocyclic group (e.g., a 5- to 7-membered ring). In some embodiments, R 8 HN-G-NHR 8 is piperazine. In some embodiments, R 8 is hydrogen or alkyl. In some embodiments, both amino groups of the diamine are primary amino groups (i.e., both R 8 groups are hydrogen), and the diamine is represented by the formula H2N-G-NH2.

[0051] In some embodiments, G is alkylene, heteroalkylene, polydiorganosiloxane, arylene, arylalkylene, alkylarylene, or combinations thereof. Suitable alkylene often has 2 to 10, 2 to 6, or 2 to 4 carbon atoms. Examples of alkylene groups include ethylene, propylene, and butylene. Suitable heteroalkylene is often polyoxyalkylene, for example, polyoxyethylene having at least two ethylene units, polyoxypropylene having at least two propylene units, or copolymers thereof. An example of polydiorganosiloxane is polydimethylsiloxane having alkylene end groups. Suitable arylalkylene groups typically contain an arylene group having 6 to 12 carbon atoms bonded to an alkylene group having 1 to 10 carbon atoms. Some examples of arylalkylene groups are phenylene-alkylene where phenylene is bonded to an alkylene having 1 to 10, 1 to 8, 1 to 6, or 1 to 4 carbon atoms. Some examples of alkylarylene groups are alkylene-phenylene where an alkylene having 1 to 10, 1 to 8, 1 to 6, or 1 to 4 carbon atoms is bonded to phenylene. When referring to group G, as used herein, "combinations thereof" refers to combinations of two or more groups selected from alkylene, heteroalkylene, polydiorganosiloxane, arylene, arylalkylene, and alkylarylene. The combination can be, for example, arylalkylene bonded to alkylene (e.g., alkylene-arylene-alkylene). In one example of an alkylene-arylene-alkylene combination, the arylene is phenylene and each alkylene has 1 to 10, 1 to 6, or 1 to 4 carbon atoms.

[0052] In some embodiments, the polydiorganosiloxane polyamide is a polydiorganosiloxane polyoxamide. The polydiorganosiloxane polyoxamide has the formula -B-(CO)-NH-, where B is alkylene; tends not to have a group having such a group. All of the carboxyamino groups along the backbone of the copolymeric material are typically part of an oxalylamino group (i.e., a -(CO)-(CO)-NH- group), and B is a bond. That is, any carbonyl group along the backbone of the copolymeric material is bonded to another carbonyl group and is part of an oxalyl group. More specifically, the polydiorganosiloxane polyoxamide has a plurality of amine oxalylamino groups.

[0053] The polydiorganosiloxane polyamide is a block copolymer and may be an elastomeric material. Unlike many known polydiorganosiloxane polyamides that are generally formulated as brittle solids or hard plastics, the polydiorganosiloxane polyamide can be formulated to contain more than 50 weight percent of a polydiorganosiloxane segment based on the weight of the copolymer. The weight percent of the diorganosiloxane in the polydiorganosiloxane polyamide can be increased by using a higher molecular weight polydiorganosiloxane segment to impart more than 60 weight percent, more than 70 weight percent, more than 80 weight percent, more than 90 weight percent, more than 95 weight percent, or more than 98 weight percent of a polydiorganosiloxane segment in the polydiorganosiloxane polyamide. A greater amount of polydiorganosiloxane can be used to prepare an elastomeric material having a lower modulus of elasticity while maintaining reasonable strength.

[0054] Some of the polydiorganosiloxane polyamides can be heated to a temperature of up to 200 °C (about 473.15 K), up to 225 °C (about 498.15 K), up to 250 °C (about 523.15 K), up to 275 °C (about 548.15 K), or up to 300 °C (about 573.15 K) without significant degradation of the material. For example, when heated in a thermogravimetric analyzer in the presence of air, the copolymer often has a weight loss of less than 10 percent when scanned at a rate of 50 °C (about 323.15 K) per minute in the range of 20 °C (about 293.15 K) to 350 °C (about 623.15 K). In addition, the copolymer can often be heated in air for 1 hour, for example, at a temperature of 250 °C (about 523.15 K), without obvious degradation as determined by the absence of a detectable loss of mechanical strength upon cooling. The linear block copolymer having the repeating unit of formula I can be prepared, for example, by the reaction of at least one polydiorganosiloxane-containing precursor having at least one diamine described in U.S. Patent No. 7,371,464, which is incorporated herein by reference.

[0055] The diamine may be classified as an organic diamine or a polydiorganosiloxane diamine having an organic diamine, including, for example, those selected from alkylenediamines, heteroalkylenediamines (e.g., polyoxyalkylenediamines), arylenediamines, aralkylenediamines, or alkylene-aralkylenediamines. The diamine has only two amino groups such that the resulting polydiorganosiloxane polyoxamide is often elastomeric, thermally melt processable (e.g., the copolymer can be processed at high temperatures, e.g., up to 250° C. (about 523.15 K) or more, without significant degradation of the composition), and soluble in some common organic solvents. In some embodiments, the diamine does not include polyamines having more than two primary or secondary amino groups. Tertiary amines that do not react with the polydiorganosiloxane-containing precursor may also be present. Additionally, the diamine utilized in the reaction does not include any carboxyamino groups. That is, the diamine is not an amide.

[0056] Preferred alkylenediamines (i.e., where G is alkylene) include, but are not limited to, ethylenediamine, propylenediamine, butylenediamine, hexamethylenediamine, 2-methylpentamethylene 1,5-diamine (i.e., commercially available from DuPont, Wilmington, DE under the trade name DYTEK A), 1,3-pentanediamine (commercially available from DuPont under the trade name DYTEK EP), 1,4-cyclohexanediamine, 1,2-cyclohexanediamine (commercially available from DuPont under the trade name DHC-99), 4,4'-bis(aminocyclohexyl)methane, and 3-aminomethyl-3,5,5-trimethylcyclohexylamine.

[0057] Polydiorganosiloxane polyoxamide copolymers can be made using a plurality of polydiorganosiloxane precursors, a plurality of diamines, or combinations thereof. A plurality of precursors having different average molecular weights can be combined under reaction conditions with a single diamine or a number of diamines. For example, the precursors can include a mixture of materials having different n values, different p values, or both different n and p values. A number of diamines can include, for example, a first diamine that is an organic diamine and a second diamine that is a polydiorganosiloxane diamine. Similarly, a single precursor can be combined under reaction conditions with a number of diamines.

[0058] Any suitable reactor or process can be used to prepare the polydiorganosiloxane polyamide copolymer material. The reaction can be carried out using a batch process, a semi-batch process, or a continuous process. An exemplary batch process can be carried out in a reaction vessel equipped with a mechanical stirrer, such as a Brabender mixer, provided that the product of the reaction in the molten state has a viscosity low enough to be discharged from the reactor. An exemplary semi-batch process can be carried out in a continuous stirred tube, tank, or fluidized bed. An exemplary continuous process can be carried out in a single-screw or twin-screw extruder, such as a wiped-surface counter-rotating or co-rotating twin-screw extruder.

[0059] The polydiorganosiloxane-containing precursor can be prepared by any known method. In some embodiments, this precursor is prepared according to the following reaction scheme described in the aforementioned U.S. Patent No. 7,371,464 (Sherman et al.).

Chemical formula

[0060] Polydiorganosiloxane diamines can be prepared by any known method and can have any suitable molecular weight.

[0061] Further details on suitable polyorganosiloxane polyamides (including polyorganosiloxane diamines and especially polyorganosiloxane polyoxamides) can be found, for example, in U.S. Patent No. 8,586,668 (Leir et al.), U.S. Patent No. 5,214,119 (Leir et al.), U.S. Patent No. 5,461,134 (Leir et al.), U.S. Patent No. 5,512,650 (Leir et al.), and U.S. Patent No. 7,371,464 (Sherman et al.), as well as U.S. Patent No. 7,705,101 and U.S. Patent No. 8,431,671 (Sherman et al.). Some polyorganosiloxane diamines are commercially available, for example, from Shin Etsu Silicones of America, Inc., Torrance, CA, and from Gelest Inc., Morrisville, PA.

[0062] Other examples of suitable silicone elastomers include polydiorganosiloxane polyureas. Copolymers and blends thereof, such as those described in U.S. Patent No. 5,461,134 and U.S. Patent No. 6,007,914 (Joseph et al.), are included. Examples of silicone-polyurethane copolymers (SPUs) useful as film-forming polymers in the compositions and methods according to the present disclosure include block copolymers containing silicone blocks and second blocks derived from polyfunctional isocyanates. In several places herein, the term silicone-polyurea may be used interchangeably with silicone-polyurethane. Useful silicone polyurea block copolymers are described, for example, in U.S. Patent No. 5,512,650; U.S. Patent No. 5,214,119; U.S. Patent No. 5,461,134; U.S. Patent No. 6,569,521; and U.S. Patent No. 6,664,359 (Melancon et al.) and International Publication No. 96 / 35458 Pamphlet, International Publication No. 98 / 17726 Pamphlet, International Publication No. 96 / 34028 Pamphlet, International Publication No. 96 / 34030 Pamphlet, and International Publication No. 97 / 40103 Pamphlet.

[0063] The block derived from the isocyanate may have two functional groups (e.g., -NHCONH- or -NHC(O)O-) attached to a divalent organic radical (e.g., an alkyl group, cycloalkyl group, and aryl group containing 1 to 30 carbon atoms). Examples of useful diisocyanate compounds from which the second block may be derived are ethylene diisocyanate, 1,6-hexylene diisocyanate, 1,12-dodecylene diisocyanate, 4,4'-diphenylmethane diisocyanate, 3,3'-dimethoxy-4,4'-diphenylmethane diisocyanate, 3,3'-dimethyl-4,4'-diphenylmethane diisocyanate, 4,4'-diphenyldiisocyanate, a mixture of toluene-2,6,-diisocyanate, toluene-2,6-diisocyanate and toluene-2,4-diisocyanate, 1,4-cyclohexylene diisocyanate, 4,4'-dicyclohexylmethane diisocyanate, 3,3'-diphenyl-4,4'-biphenylene diisocyanate, 4,4'-biphenylene diisocyanate, 2,4-diisocyanatodiphenyl ether, 2,4-dimethyl-1,3-phenylene diisocyanate, 4,4'-diphenyl ether diisocyanate, isophorone diisocyanate, and mixtures thereof.

[0064] The silicone block has the general formula (Si(R 7 )2O-): wherein R 7 is as defined above for any of the embodiments of R 7 in Formula I; and includes those having. As non-limiting examples, dimethyl silicone, diethyl silicone, and diphenyl silicone are included.

[0065] The polydiorganosiloxane urethane-containing copolymers (a subset of the class of SPU materials) useful in the compositions of the present disclosure contain soft polydiorganosiloxane units, hard polyisocyanate residue units, end groups and optionally soft and / or hard organic polyamine residue units. Some polydiorganosiloxane urea-containing copolymers are commercially available under the trade name "GENIOMER 140" available from Wacker Chemie AG, Germany. The polyisocyanate residue is what remains after removing the -NCO group from the polyisocyanate, the organic polyamine residue is what remains after removing the -NH group from the organic polyamine, and the polyisocyanate residue is connected to the polydiorganosiloxane unit or the organic polyamine residue by a urea linking group. The end groups may be non-functional or functional depending on the purpose of the polydiorganosiloxane urea segmented copolymer.

[0066] In some embodiments, the polydiorganosiloxane urethane containing a copolymer useful as a polymer processing additive contains at least two repeating units of Formula II.

Chemical formula

[0067] In this Formula II, each R 9 is a moiety that is independently an alkyl, cycloalkyl, aryl, perfluoroalkyl, or perfluoroether group. In some embodiments of R 9 , the alkyl has from about 1 to 12 carbon atoms and is, for example, trifluoroalkyl, vinyl, vinyl radical, or a higher alkenyl represented by the formula -R 10 (CH2) a CH=CH2: wherein R 10 is -(CH2) b - or -(CH2) c CH=CH- and a is 1, 2 or 3; b is 0, 3 or 6; c is 3, 4 or 5; and may be substituted by a higher alkenyl. R 9In some embodiments, the cycloalkyl has from about 6 to 12 carbon atoms and may be substituted with one or more alkyl, fluoroalkyl, or vinyl groups. R 9 In some embodiments, the aryl has from about 6 to 20 carbon atoms and may be substituted, for example, with alkyl, cycloalkyl, fluoroalkyl, and vinyl groups. R 9 In some embodiments, the perfluoroalkyl group is as described in U.S. Patent No. 5,028,679, the detailed description of which is incorporated herein by reference, and the perfluoroether-containing group is as described in U.S. Patent Nos. 4,900,474 and 5,118,775, the detailed descriptions of which are incorporated herein by reference. In some embodiments, R 9 is a fluorine-containing group as described in U.S. Patent No. 5,236,997, the detailed description of which is incorporated herein by reference. In some embodiments, R 9At least 50% of the moiety is a methyl radical, and the remainder is a monovalent alkyl or substituted alkyl radical having from 1 to 12 carbon atoms, an alkenylene radical, a phenyl radical, or a substituted phenyl radical. In Formula II, each Z’ is an arylene, arylalkylene, alkylene, or cycloalkylene. In some embodiments of Z’, the arylene or arylalkylene has from about 6 to 20 carbon atoms. In some embodiments of Z’, the alkylene or cycloalkylene radical has from about 6 to 20 carbon atoms. In some embodiments, Z’ is 2,6-tolylene, 4,4’-methylenediphenylene, 3,3’-dimethoxy-4,4’-biphenylene, tetramethyl-m-xylylene, 4,4’-methylenedicyclohexylene, 3,5,5-trimethyl-3-methylenecyclohexylene, 1,6-hexamethylene, 1,4-cyclohexylene, 2,2,4-trimethylhexylene, or a mixture thereof. In Formula II, each Y’ is independently an alkylene, arylalkylene, alkylarylene, or arylene. In some embodiments of Y’, the alkylene has from 1 to 10 carbon atoms. In some embodiments of Y’, the arylalkylene, alkylarylene, or arylene has from 6 to 20 carbon atoms. In Formula II, each D is independently hydrogen, an alkyl radical having from 1 to 10 carbon atoms, phenyl, or a radical that completes a ring structure containing radical B’ or Y’ to form a heterocycle. In Formula II, B is a polyvalent radical selected from the group consisting of alkylene, arylalkylene, alkylarylene, cycloalkylene, phenylene, polyalkylene oxide (e.g., polyethylene oxide, polypropylene oxide, polytetramethylene oxide, and copolymers and mixtures thereof). In Formula II, “s” is a number from 0 to about 1000; “r” is a number of 1 or greater; “q” is a number that is about 5 or greater, in some embodiments about 15 to 2000, and in some embodiments about 30 to 1500.

[0068] In the use of a polyisocyanate (Z' is a radical having a functionality greater than 2) and a polyamine (B' is a radical having a functionality greater than 2), the structure of formula II is modified to reflect branching in the polymer backbone. In the use of an end-capping agent, the structure of formula II is modified to reflect the termini of the polydiorganosiloxane urea chains.

[0069] Linear block copolymers having the repeating unit of formula I and the polydiorganosiloxane urea-containing polymer of formula II can be prepared, for example, as discussed in U.S. Patent No. 8,552,136 (Papp et al.).

[0070] Other examples of silicone-containing polymers include those formed from silanols, hydrosilicones, siloxanes, epoxides, and (meth)acrylates. When a film-forming polymer is prepared from a (meth)acrylate-functional siloxane, the polymer may be referred to as a siloxane (meth)acrylate. In addition, other amphiphilic siloxy-containing polymers have been reported to be useful in gel compositions (U.S. Patent No. 7,795,326 (Salamone et al.)), and hydrophobic siloxysilane monomers have been copolymerized with hydrophilic nitrogen-containing monomers. Other siloxy-containing polymers include block copolymers of polydimethylsiloxane and polyurethane, and block copolymers of polydimethylsiloxane and poly(ethylene glycol). Still other potentially promising film-forming polymers include block copolymers of polystyrene and ethylene / butylene, block copolymers of polystyrene and polyisobutylene, block copolymers of polystyrene and polyisoprene, block copolymers of polystyrene and polybutadiene, block copolymers of polydimethylsiloxane and polyurethane, polymers of C4-C18 acrylates and methacrylates, butyl rubber, polyisobutylene, and combinations thereof.

[0071] Another suitable siloxy-containing monomer for a particular gel composition is based on the siloxy monomer, 3-methacryloyloxypropyltris(trimethylsiloxy)silane (TRIS). TRIS can be used in combination with both hydrophilic comonomers, such as N-isopropylacrylamide (NIPAM), or hydrophobic comonomers, such as methyl methacrylate, such that the resulting copolymer is soluble in a volatile solvent.

[0072] The film-forming polymer is typically present in an amount of at least 5% by weight and up to 30% by weight, or any amount within such range, based on the total weight of the gel composition. In certain embodiments, the film-forming polymer may preferably be present at a concentration of at least 12% by weight and up to 25% by weight based on the total weight of the gel composition.

[0073] The dried film cast from the gel composition may contain the film-forming polymer in an amount in the range of 50% to 70% or 75% by weight, or any amount within such range, based on the total weight of the dried film.

[0074] Alternatively, the gel composition may feature a polymerizable cyanoacrylate monomer as the main film-forming polymer. Examples of cyanoacrylate monomers that can be used include alkyl cyanoacrylates, aryl cyanoacrylates, alkoxyalkyl cyanoacrylates, such as butyl cyanoacrylate and n-butyl cyanoacrylate, particularly octyl cyanoacrylate and 2-octyl cyanoacrylate, especially ethyl cyanoacrylate, methyl cyanoacrylate, n-dodecyl cyanoacrylate, phenyl 2-cyanoacrylate, methoxyethyl 2-cyanoacrylate, and readily polymerizable alpha-cyanoacrylates including the like. The composition may consist of one or more polymerizable cyanoacrylate monomers. Film-forming cyanoacrylates are as discussed in U.S. Patent No. 6,183,593 (Narang et al.) and U.S. Patent No. 6,143,805 (Hickey et al.). Polymerizable cyanoacrylate esters are particularly described in U.S. Patent Application Publication No. 2008 / 0152614 (Dunshee). Further cyanoacrylate compositions are also disclosed in U.S. Patent No. 5,480,935 (Greff et al.).

[0075] Adhesion promoter An adhesion promoter, such as a silicate adhesion-promoting resin, can be added to the film-forming polymer to impart or improve the adhesion properties of the composition. The silicate adhesion-promoting resin can affect the physical properties of the resulting gel composition. For example, as the silicate adhesion-promoting resin content increases, the transition of the gel composition from a glassy state to a rubbery state will occur at a gradually higher temperature. In some exemplary gel compositions, multiple silicate adhesion-promoting resins can be used to obtain the desired performance. Suitable silicate adhesion-promoting resins have the following structural units M (i.e., monovalent R’3SiO 1 / 2 unit), D (i.e., divalent R’2SiO 2 / 2 unit), T (i.e., trivalent R’SiO 3 / 2 unit), and Q (i.e., quaternary SiO 4 / 2Such resins are included which are composed of units and combinations thereof. Typical exemplary silicate resins include MQ silicate tackifying resins, MQD silicate tackifying resins, and MQT silicate tackifying resins. These silicate tackifying resins typically have a number average molecular weight in the range of 100 to 50,000 or in the range of 500 to 15,000 and generally have methyl R' groups.

[0076] Such resins are described, for example, in Encyclopedia of Polymer Science and Engineering, vol. 15, John Wiley & Sons, New York, (1989), pp. 265 - 270, as well as in U.S. Patent No. 2,676,182 (Daudt et al.), U.S. Patent No. 3,627,851 (Brady), U.S. Patent No. 3,772,247 (Flannigan), and U.S. Patent No. 5,248,739 (Schmidt et al.). Other examples are disclosed in U.S. Patent No. 5,082,706 (Tangney). The above resins can generally be prepared in a solvent. Dry or solvent - free M silicone tackifying resins can be prepared as described in U.S. Patent No. 5,319,040 (Wengrovius et al.), U.S. Patent No. 5,302,685 (Tsumura et al.), and U.S. Patent No. 4,935,484 (Wolfgruber et al.).

[0077] MQ silicate tackifying resins are particularly suitable for some of the gel compositions of the present disclosure. The MQ silicate tackifying resin is a copolymeric resin having R'3SiO 1 / 2 units (the "M" units) and SiO 4 / 2 units (the "Q" units), where the M units are bonded to the Q units and each is bonded to at least one other Q unit. Some of the SiO 4 / 2 units (the "Q" units) are bonded to a hydroxyl radical, resulting in HOSiO 3 / 2 units (the "T OH」 units), thereby accounting for the silicon-bonded hydroxyl groups of the silicate tackifying resin, some of which are bonded only to other SiO 4 / 2 units.

[0078] A particular MQ silicate tackifying resin can be prepared by the silica hydrosol capping process described in U.S. Patent No. 2,676,182 (Daudt et al.), as modified by U.S. Patent No. 3,627,851 (Brady) and U.S. Patent No. 3,772,247 (Flannigan). These modified processes often involve restricting the concentration of the sodium silicate solution, and / or the silicon-to-sodium ratio in the sodium silicate, and / or the time before capping the neutralized sodium silicate solution to generally lower values than those disclosed by Daudt et al. The neutralized silica hydrosol is often stabilized with an alcohol, such as 2-propanol, and capped with R3SiO 1 / 2 siloxane units as soon as possible after neutralization. The level of silicon-bonded hydroxyl groups (i.e., silanols) in the MQ resin may be reduced to 1.5 weight percent or less, 1.2 weight percent or less, 1.0 weight percent or less, or 0.8 weight percent or less, based on the weight of the silicate tackifying resin. This can be achieved, for example, by reacting hexamethyldisilazane with the silicate tackifying resin. Such a reaction may be catalyzed, for example, by trifluoroacetic acid. Alternatively, trimethylchlorosilane or trimethylsilylacetamide may be reacted with the silicate tackifying resin, in which case a catalyst is not required.

[0079] The tackifier is typically added to the composition at at least 2% by weight, in some embodiments at least 3% by weight, in some embodiments at least 4% by weight, in some embodiments at least 5% by weight, based on the total weight of the gel composition. The tackifier is typically present in the composition at 20% by weight or less, more preferably 15% by weight or less, and most preferably 10% by weight or less, based on the total weight of the composition.

[0080] The dried film cast from the gel composition may contain from 5% to 25% or 30% by weight, or any amount within such range, of the tackifier, based on the total weight of the dried film. In certain embodiments, films characterized by less than 16% by weight of the tackifier exhibit less adhesion to the skin or other tissues than may be desired.

[0081] Coagulant In certain advantageous embodiments, the gel composition contains a coagulant and a cationic polymer that acts as a reservoir, with respect to a particular volume of exudate. This cationic polymer typically includes a crosslinked guanidinyl-containing polymer. The base polymer in the guanidinyl-containing polymer typically includes a polyamine polymer; i.e., a polymer having primary or secondary amino groups that may be polymer pendant or catenary in the polymer chain. The amino polymer contains primary or secondary amine groups and can be prepared by chain growth or sequential polymerization procedures with the corresponding monomers. These monomers may also be copolymerized with other monomers, if desired. The polymer may also be a synthetic or natural biopolymer. Regardless of the source, when any of these polymers do not contain primary or secondary amine groups, these functional groups can be added by appropriate graft chemistry.

[0082] Useful aminopolymers are water-soluble or water-dispersible. As used herein, the term "water-soluble" refers to a material that can be dissolved in water. The solubility is typically at least about 0.1 g / mL of water. As used herein, the term "water-dispersible" refers to a material that is not water-soluble but can be emulsified or suspended in water.

[0083] Examples of aminopolymers prepared by chain-growth polymerization and suitable for use include, but are not limited to: polyvinylamine, poly(N-methylvinylamine), polyallylamine, polyallylmethylamine, polydiallylamine, poly(4-aminomethylstyrene), poly(4-aminostyrene), poly(acrylamide-co-methylaminopropylacrylamide), and poly(acrylamide-co-aminoethylmethacrylate).

[0084] Examples of aminopolymers prepared by sequential polymerization and suitable for use include, but are not limited to: polyethyleneimine, polypropyleneimine, polylysine, polyaminoamide, polydimethylamine-epichlorohydrin-ethylenediamine, and any of a number of polyaminosiloxanes that can be constructed from monomers such as aminopropyltriethoxysilane, N-(2-aminoethyl)-3-aminopropyltrimethoxysilane, N-trimethoxysilylpropyl-N-methylamine, and bis(trimethoxysilylpropyl)amine.

[0085] Useful amino polymers having a primary or secondary amino terminal group include, but are not limited to, those formed from polyamidoamine (PAMAM) and polypropyleneimine: for example, DAB-Am and PAMAM dendrimers (or highly branched polymers containing amine or quaternary nitrogen functional groups). Exemplary dendrimeric materials formed from PAMAM are commercially available from Aldrich Chemical, Milwaukee, Wis under the trade name Starburst™ (PAMAM) dendrimers (e.g., generation 0 having 4 primary amino groups, generation 1 having 8 primary amino groups, generation 2 having 16 primary amino groups, generation 3 having 32 primary amino groups, and generation 4 having 64 primary amino groups). Dendrimeric materials formed from polypropyleneimine are commercially available from Aldrich Chemical under the trade name DAB-AM. For example, DAB-Am-4 is a generation 1 polypropyleneimine tetraamine dendrimer having 4 primary amino groups, DAB-Am-8 is a generation 2 polypropyleneimine octaamine dendrimer having 8 primary amino groups, DAB-Am-16 is a generation 3 polypropyleneimine hexadecaamine having 16 primary amino groups, DAB-Am-32 is a generation 4 polypropyleneimine dotriacontaamine dendrimer having 32 primary amino groups, and DAB-Am-64 is a generation 5 polypropyleneimine tetrahexacontaamine dendrimer having 64 primary amino groups.

[0086] Examples of amino polymers suitable for use that are biopolymers include chitosan and starch, the latter of which is grafted with a reagent such as methylaminoethyl chloride.

[0087] Other categories of amino polymers suitable for use include polyacrylamide homopolymers, or copolymers with amino monomers including aminoalkyl (meth)acrylates, (meth)acrylamide alkylamines, and diallylamine. Currently preferred amino polymers include polyaminoamides, polyethyleneimines, polyvinylamines, polyallylamines, and polydiallylamines.

[0088] Suitable commercially available amino polymers include, but are not limited to, polyamidoamines such as ANQU Amine™ 360, 401, 419, 456, and 701 (Air Products and Chemicals, Allentown, Pa.); LUPASOL™ polyethyleneimine polymers such as FG, PR 8515, Waterfree, P, PS (BASF Corporation, Resselaer, N.Y.); polyethyleneimine polymers such as CORCAT™ P-600 (EIT Company, Lake Wylie, S.C.); polyoxyalkylene amines such as JEFF AMINE™ D-230, D-400, D-2000, HK-511 (XTJ-511), XTJ-510 (D-4000), XTJ-500 (ED-600), XTJ-502 (ED-2003), T-403, XTJ-509 (T-3000), and T-5000 (Huntsman Corporation, Houston, Tex.); and polyamide resins such as the VERSAMID series of resins formed by reacting dimerized unsaturated fatty acids with alkylene diamines (Cognis Corporation, Cincinnati, Ohio).

[0089] The coagulant can be prepared by the condensation of a polyamine polymer with a guanidylating agent. Known guanidylating agents include: cyanamide; O-alkylisourea salts such as O-methylisourea sulfate, O-methylisourea hydrogen sulfate, O-methylisourea acetate, O-ethylisourea hydrogen sulfate, and O-ethylisourea hydrochloride; chloroformamidine hydrochloride; 1-amidino-1,2,4-triazole hydrochloride; 3,5-dimethylpyrazole-1-carboxamidine nitrate; pyrazole-1-carboxamidine hydrochloride; N-amidinopyrazole-1-carboxamidine hydrochloride; and carbodiimides such as dicyclohexylcarbodiimide, N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide, and diisopropylcarbodiimide. The polyamine polymer may be acetylated with a guanidino-functional carboxylic acid such as guanidinoacetic acid and 4-guanidinobutyric acid in the presence of an activator such as EDC (N-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride) or EEDQ (2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline). In addition, the cationic polymer may be prepared by alkylation with chloroacetone guanylhydrazone as described in U.S. Patent No. 5,712,027.

[0090] As reagents for the preparation of biguanide-functional polymers, sodium dicyanamide, dicyandiamide, and substituted cyanoguanidines such as N 3 -p-chlorophenyl-N 1 -cyanoguanidine, N 3 -phenyl-N 1 -cyanoguanidine, N 3 -alpha-naphthyl-N 1 -cyanoguanidine, N 3 -methyl-N 1 -cyanoguanidine, N 3 ,N 3 -dimethyl-N 1 -cyanoguanidine, N 3 -(2-hydroxyethyl)-N 1 -cyanoguanidine, and N 3 -butyl-N1 - Cyanoguanidine can be mentioned. Alkylene- and arylene biscyanoguanidines can be utilized to prepare biguanide-functional polymers by a chain extension reaction. The preparation of cyanoguanidine and biscyanoguanidine is described in detail in Rose, F. L. and Swain, G. J. Chem Soc., 1956, pp. 4422 - 4425. Other useful guanylation reagents are described by Alan R. Katritzky et al., Comprehensive Organic Functional Group Transformation, Vol. 6, p. 640. Generally, such guanylation reagents are used in an amount sufficient to functionalize 0.5 to 100 mole percent, preferably 2.5 to 50 mole percent, of the available amino groups of the amino polymer.

[0091] The resulting polymer has pendant or chain guanidinyl groups of formula III.

Chemical formula

[0092] The guanidinyl-containing polymer can be crosslinked. The amino-containing polymer can be crosslinked before reaction with the guanidinating agent. Alternatively, the guanidinyl-containing polymer can be crosslinked by reaction with a crosslinking agent and some of the remaining amino groups from the amino-containing polymer precursor or guanidinyl groups. Suitable crosslinking agents include amine-reactive compounds such as bis and polyaldehydes such as glutaraldehyde, bis and polyglycidyl ethers such as butanediol diglycidyl ether and ethylene glycol diglycidyl ether, polycarboxylic acids and their derivatives (such as acid chlorides), polyisocyanates, formaldehyde-based crosslinking agents such as those derived from hydroxymethyl and alkoxymethyl functional crosslinking agents such as urea or melamine, and amine-reactive silanes such as 3-glycidoxypropyltrimethoxysilane, 3-glycidoxypropyltriethoxysilane, 5,6-epoxyhexyltriethoxysilane, (p-chloromethyl)phenyltrimethoxysilane, chloromethyltriethoxysilane, 3-isocyanatopropyltriethoxysilane, and 3-thiocyanatopropyltriethoxysilane.

[0093] In other embodiments, the gel composition includes a hemostatic agent such as a polymerizable cyanoacrylate monomer. Other coagulants include microfibrillar collagen, chitosan, bone wax, ostene, oxidized cellulose, and thrombin.

[0094] When included, the coagulant is typically present in an amount of at least 0.5% by weight and up to 20% by weight, or any amount within such range, based on the total weight of the gel composition. In certain embodiments, the coagulant is preferably present at a concentration of at least 1% by weight and up to 15% by weight, and in still other embodiments at least 1.5% by weight and up to 10% by weight, or any amount within such range.

[0095] The dried film cast from the gel composition may contain a coagulant in an amount in the range of 5 wt% to 30 or 35 wt% of the total weight of the dried film, or any amount within such range. In certain situations, depending on the particle size, the coagulant may remain on the surface of the film during treatment, migrate to the wound or target area, and assist in localized coagulation, or may be some combination of these. The film can act as a coagulant delivery system to the underlying target area in these situations.

[0096] When a silicone-containing film-forming polymer is used, a silicone surfactant can be incorporated to help stabilize the coagulant in the gel composition. Examples of silicone surfactants typically include polydimethylsiloxane (PDMS) fluids and / or organo-modified PDMS fluids, such as siloxane polyether copolymers. One exemplary suitable PDMS surfactant is monocarboxyl decyl-terminated polydimethylsiloxane (available from Gelest LTD, Kent, UK as MCR-B-12). Another suitable PDMS surfactant is Abil Quat 3272 available from Evonik Goldschmidt, Germany. Another suitable surfactant is dimethoxymethylsilylpropyl-polyethyleneimine-50% in IPA available from Gelest. In certain situations, the silicone surfactant can improve the adhesion of the gel (and the resulting dried film) to the tissue.

[0097] When present, the silicone surfactant is typically present in an amount of at least 0.1 wt% and up to 15 wt% based on the total weight of the gel composition. The dried film cast from the gel composition may contain a silicone surfactant in an amount in the range of 1 wt% to 15 wt% or 20 wt% of the total weight of the dried film, or any amount within such range.

[0098] In certain formulations characterized by a guanidinyl-containing polymer as a gelling agent, it can be useful to include relatively small amounts of silicone surfactant or none at all. In such compositions, the silicone surfactant is present in an amount of 0.25 wt% or less, based on the total weight of the gel composition. The Applicants have found some evidence that, in contrast to the expected stabilization, inclusion above 0.25 wt% can (in certain circumstances) reduce the stability of the composition beyond the otherwise expected shelf life.

[0099] Amine-rich adhesion promoter Instead of or in addition to gelling agents and tackifiers, the gel compositions of the present disclosure may include an amine-rich adhesion promoter. The amine-rich adhesion promoter can be, in presently preferred circumstances, an aminosilicone. Other suitable amine-rich adhesion promoters include polymeric cationic ammonium compounds such as polyhexamethylene biguanide (i.e., polyaminopropyl biguanide) and certain specific aminopolymers that function as bases for guanidinyl-containing gelling agents.

[0100] The Applicants have found that certain amine-rich compounds promote skin adhesion without adversely affecting the rheology of the gel composition or the properties of the film formed from such gel composition. Further, these adhesion promoters can enable improved adhesion with little tackifier present in the gel composition and can be important for maintaining the integrity of the film formed on the skin. In particular, these compounds having an amine number greater than 25 are said to impart a desired skin adhesion (e.g., at least 25 g / inch (about 2.54 cm)) even in the absence of a gelling agent, a tackifier, or both. In the present disclosure, "amine number" represents the number of milliliters of 0.1 N HC1 required to neutralize 10 g of the amine-rich adhesion promoter. The amine number is preferably calculated according to the following formula: 1 / FGMW * ×100,000, wherein, *FGMW = molecular weight of the functional group of the amine group.

[0101] In some embodiments, the adhesion promoter has more than 20, in some embodiments more than 25, in some embodiments more than 30, in some embodiments more than 40, in some embodiments more than 45, in some embodiments more than 50 amine numbers. Without wishing to be bound by theory, the amine content of the adhesion promoter is said to be directly related to improved adhesion to the skin among other parameters and characteristics of the promoter. Thus, an adhesion promoter suitable for use in the present gel composition advantageously typically contains a greater number of available amine groups and thus a greater amine number.

[0102] As used herein, "aminosilicone" means any amine-functionalized silicone; i.e., a silicone containing at least one primary amine, secondary amine, tertiary amine, or quaternary ammonium group. Typically, these are silicones that have been chemically modified such that some of the pendant groups along the backbone are replaced by various alkylamine groups (-R-NH2). These amine groups can become positively charged in aqueous solution due to their electron-donating tendency, resulting in an inorganic cationic polymer. Useful aminosilicones are typically water-soluble or water-dispersible.

[0103] Exemplary aminosilicones for use in embodiments of the present disclosure can be linear polymers, branched polymers, copolymers, and mixtures thereof. In some embodiments, the copolymer is a block copolymer. In some embodiments, including those of currently preferred compositions, the aminosilicone has pendants from the polymer backbone. Examples of such embodiments are shown by compounds of Formula IV having pendant mono-amines and compounds of Formula VI having pendant diamines, as shown below herein. In some embodiments, the polymer has amine groups at one or more ends of the polymer. Examples of such embodiments are shown by the compound of Formula V, as shown below herein. The aminosilicone can be further selected from the group consisting of aminodimethicone, trimethylsilylamodimethicone, aminoethylaminopropylsiloxane-dimethylsiloxane copolymer, and mixtures thereof.

[0104] In some embodiments, the aminosilicone has the structure of Formula IV.

Chemical formula

[0105] In some embodiments, one or more aminosilicones have the structure of Formula V, characterized by a terminal amine group.

Chemical formula

[0106] In other embodiments, the aminosilicone comprises a branched diamino-functional polydimethylsiloxane of Formula VI. [Chemical formula] (wherein the blocks having subscripts x and y may be randomly mixed, the total value of x is from 5 to 5,000, the total value of y is from 1 to 20, for example, 8, and R and R', which may be the same or different, are each a saturated linear or branched alkyl group having 1 to 12 carbon atoms (preferably 1 to 6), for example, R is a linear C3H6 group and R' is a linear C2H4 group.)

[0107] In some embodiments, the amino silicone is GP-4 (a compound of formula IV, where R = (CH2)3, x = 58 and y = 4, available from, for example, Genesee Polymer Corporation ("GPC"), Burton, Michigan, USA, and having about 90 amine numbers), GP-6 (a compound of formula IV, where R = (CH2)3, x = 100 and y = 4, available from, for example, GPC, and having about 49 amine numbers), GP-316 (a compound of formula III, where R = (CH2)3, R' = (CH2)2, x = 400 and y = 8, available from, for example, GPC, and having about 54 amine numbers), GP-581 (a compound of formula IV, where R = (CH2)3, x = 118 and y = 11, available from, for example, GPC, and having about 110 amine numbers), GP-965 (a compound of formula V, where R = R' = (CH2)3, x = 10, available from, for example, GPC, and having about 200 amine numbers), KF-861 (a compound of formula VI, having about 127 amine numbers, available from, for example, Shin-Etsu Silicones, Akron, OH), KF-864 (a compound of formula IV, having about 26 amine numbers, available from, for example, Shin-Etsu Silicones), KF-869 (a compound of formula VI, having about 54 amine numbers, available from Shin-Etsu Silicones), KF-393 (a diamino-modified compound of formula IV, having about 286 amine numbers, available from Shin-Etsu Silicones), KF-880 (a diamino-modified compound of formula IV, having about 56 amine numbers, available from Shin-Etsu Silicones), KF-8004 (a diamino-modified compound of formula IV, having about 67 amine numbers, available from Shin-Etsu Silicones), Silamine(R)AO EDA (a compound of formula VI, where R = (CH2)3, R' = (CH2)2, having about 230 amine numbers, Siltech Corporation, Toronto, Ontario,Available from Canada), Silamine(R) D2 EDA (a compound of formula VI, where R = (CH2)3, R’ = (CH2)2, having an amine number of about 170, available from, for example, Siltech Corporation), Silamine(R) D208 EDA (a compound of formula VI, where the dimethylsiloxane repeating unit moiety is further substituted by a polyether group, R = (CH2)3, R’ = (CH2)2, having an amine number of about 30, available from Siltech Corporation), commercial alternatives thereof (e.g., aminosilicones from other suppliers recognized by those skilled in the art), and mixtures thereof.

[0108] In a presently preferred situation, the selected aminosilicone has one or more di- or mono-amine groups pendant from the polymer backbone.

[0109] Other possible suitable aminosilicones include certain quaternary silicones. By “quaternary silicone” is understood any silicone containing one or more quaternary ammonium groups. The compositions of the present invention may comprise at least one silicone quaternary compound selected from silicone quaternium-12 (e.g., available from Phoenix Chemical, Somerville, NJ as PECOSIL CA-1240, a reaction product of cocoamidopropyldimethylamine and dimethicone PEG-7 acetyl chloride), silicone quaternium-8 (e.g., available as PECOSIL AD-3640), silicone quaternium-19 (e.g., available from Zenitech, Ontario, CA as ZENESTER Q, a functionalized cationic polymeric silicone polyester made from the reaction of a cationic dimethicone copolyol and dimer acid), silicone quaternium-22 (available as Abil T quat 60), silicone quaternium-80 (available as Abil T Quat 3272), and mixtures thereof.

[0110] Particularly preferred quaternary silicones include those sold as PECOSIL AD-3640 and PECOSIL CA-1240, each having the formula:

Chem.

[0111] Without wishing to be bound by theory, the gel compositions of the present disclosure may require a relatively greater amount of a given quaternary silicone in order to obtain the same skin adhesion performance as a suitable amino silicone and to hold the other components of the composition constant. Further, such compositions may still enjoy the benefits from the presence of the tackifier.

[0112] Examples of amino polymers suitable for use as adhesion promoters include the base polymers in the guanidinyl-containing polymers described above, including polyaminoamides, polyethyleneimine, polyvinylamine, polyallylamine, and polydiallylamine. A currently preferred amino polymer is polyethyleneimine. Polyethyleneimine (PEI) is commercially available in several forms, such as linear, branched, and dendrimeric. Linear PEI can be represented by the following formula VIII.

Chem.

[0113] An exemplary branched PEI fragment can be represented by the following formula IX.

Chem.

[0114] Dendrimeric PEI is a special case of branched PEI. An exemplary (generation 4) dendrimeric PEI is represented by the following formula X.

Chemical formula

[0115] In this case, PEI contains only primary and tertiary amino groups. Dendrimeric PEI is commercially available and / or can be prepared by known methods.

[0116] In another embodiment, the amine-rich adhesion promoter may comprise, consist essentially of, or consist of a silylated amino polymer. The silylated amino polymer may be a polyamine having at least one silane or alkoxysilane moiety attached at any position within the polyamine. The silylated polyamine may be prepared, for example, by reaction of an amine-reactive organosilane coupling agent with at least some of the primary amines present in an amino polymer, such as branched PEI. Exemplary amine-reactive organosilane coupling agents include: 3-isocyanatopropyltriethoxysilane; 3-isocyanatopropyltrimethoxysilane; 2-isocyanatoethyltriethoxysilane; 2-isocyanatoethyltrimethoxysilane; 3-acryloxypropyltriethoxysilane; 3-acryloxypropyltrimethoxysilane; 2-acryloxyethyltriethoxysilane; 2-acryloxyethyltrimethoxysilane; 3-glycidoxypropyltriethoxysilane; 3-glycidoxypropyltrimethoxysilane; 2-(3,4-epoxycyclohexyl)ethyltrimethoxysilane; and 2-(3,4-epoxycyclohexyl)ethyltriethoxysilane. The silylated polyamine may be, but is not limited to, silylated polyethyleneimine (SPEIm), silylated polyvinylpyridine, silylated poly(dimethylaminoethyl methacrylate), silylated polyvinylamine, silylated polyallylamine (PAAm), or combinations thereof. In an alternative embodiment, the silylated polyamine comprises or is trimethoxysilylpropyl-modified polyethyleneimine.

[0117] When included instead of or in addition to the coagulant, the amine-rich adhesion promoter is typically present in an amount of at least 0.5 wt% and up to 20 wt%, or any amount within such range, based on the total weight of the gel composition. In certain embodiments, the amine-rich adhesion promoter is preferably present in a concentration of at least 1 wt% and up to 15 wt%, and in still other embodiments at least 1.5 wt% and up to 10 wt%, or any amount within such range, based on the total weight of the gel composition.

[0118] The dried film cast from the gel composition may contain an amine-rich adhesion promoter in an amount in the range of 5 wt% to 30 wt% or 35 wt%, or any amount within such range, based on the total weight of the dried film.

[0119] When included in the gel composition instead of both the coagulant and the tackifier, the adhesion promoter is typically added to the composition in an amount of at least 2.5 wt%, in some embodiments at least 4 wt%, and in some embodiments at least 5 wt%, based on the total weight of the gel composition. In such compositions, the amine-rich adhesion promoter is typically present in the composition in an amount of up to 35 wt%, more preferably up to 25 wt%, and most preferably up to 20 wt%, based on the total weight of the composition.

[0120] The dried film cast from a gel composition lacking a coagulant or a tackifier may contain an amine-rich adhesion promoter in an amount in the range of 10 wt% to 55 wt% or 60 wt%, or any amount within such range, based on the total weight of the dried film.

[0121] Solvent The coating gel composition further includes a volatile solvent. In one embodiment, the volatile solvent is selected from the group consisting of volatile linear and cyclic siloxanes, volatile polydimethylsiloxanes, isooctane, octane, and combinations thereof. The solvent is typically at least 40 wt% of the total gel composition. When the composition may be applied to tissue, the solvent is desirably volatile and non-irritating. In one embodiment, at least 60 wt% of the total composition is the solvent. In still other embodiments, the solvent is present at least 70 wt% of the total composition.

[0122] The solvent system for the gel compositions of the present disclosure can be a nonpolar volatile solvent, such as isooctane. Other exemplary volatile solvent systems include, in addition to liquid carbon dioxide, linear or cyclic siloxanes, such as hexamethyldisiloxane (HMDS), octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, and octamethyltrisiloxane, or linear, branched, or cyclic alkanes, such as propane, isobutane, liquid butane (e.g., under pressure), pentane, hexane, heptane, octane, petroleum distillates, cyclohexane, fluorocarbons, such as trichloromonofluoromethane, dichlorodifluoromethane, dichlorotetrafluoroethane, tetrafluoroethane, heptafluoropropane, 1,1-difluoroethane, pentafluoropropane, perfluoroheptane, perfluoromethylcyclohexane, 1,1,1,2,-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoropropane, chlorofluorocarbons, and combinations thereof. As used herein, "volatile" has its standard meaning, i.e., it can rapidly evaporate at normal temperature and pressure. For example, a solvent can be volatile when a 1-meter drop (1 / 20 mL, 50 μL) of the solvent completely evaporates within 5 minutes, or within 4 minutes, or within 3 minutes, or within 2 minutes, or within 1 minute, or within 30 seconds, or within 15 seconds at 20-25 °C (about 293.15 - about 298.15 K).

[0123] The use of non-polar volatile solvents, alone or in combination, as the primary liquid phase of a gel composition can impart the desired balance between fast drying and reduced skin irritation upon application. In presently preferred embodiments, the solvent is one of HMDS and isooctane. Other, more polar solvents, such as ethanol, isopropanol, glycerin, N-methylpyrrolidone, and N,N-dimethylacetamide may be used in other embodiments, and a non-stinging gel composition is either unnecessary or undesirable. A number of aprotic solvents, including acetates, such as methyl acetate and ethyl acetate, propylene glycol diacetate, volatile ketones, such as acetone and methyl ethyl ketone, volatile ethers, such as diethyl ether, ethyl propyl ether, dipropyl ether and dipropylene glycol dimethyl ether, volatile fluorocarbons, such as pentafluoropropane, perfluoroheptane, perfluoromethylcyclohexane, and the like, have utility; or volatile gases, such as carbon dioxide can also be used, each with varying degrees of user discomfort.

[0124] In some embodiments, water can be included in a solvent system that can be useful for solubilizing certain active agents and hemostatic agents. In certain embodiments, for example, a relatively small amount of water, at least 0.1% by weight based on the total weight of the composition, is present in the gel composition. In other embodiments, the water content is at least 60% by weight based on the total weight of the composition, but such compositions may require a longer drying time than is presently desired. Certain solvent systems containing water are exemplified in U.S. Patent No. 7,651,990 (Asmus), and U.S. Patent No. 8,338,491 (Asmus et al.).

[0125] Additives The gel compositions of the present disclosure may include fillers. Examples of suitable fillers are natural or synthetic materials, including but not limited to: quartz (i.e., silica, SiO2); nitrides (e.g., silicon nitride); glasses and fillers derived from, for example, Zr, Sr, Ce, Sb, Sn, Ba, Zn, and Al; feldspar; borosilicate glass; kaolin (china clay); talc; zirconia; titania; and submicron silica particles (e.g., fumed silica, such as those available under the trade name AEROSIL, "OX50", "OX130", "OX150", and "OX200" silica from Degussa Corp., Akron, OH, and CAB-O-SIL M5 and TS-720 silica from Cabot Corp., Tuscola, IL). Organic fillers made from polymeric materials are also possible, for example, as disclosed in PCT Application No. WO 09 / 045752 pamphlet (Kalgutkar et al.).

[0126] Clay materials suitable for use in the compositions, methods, and articles of the present disclosure include those in geological classifications, smectites, kaolins, illites, chlorites, serpentines, attapulgites, palygorskites, vermiculites, glauconites, sepiolites, and mixed-layer clays. Examples of smectites include, for example, montmorillonite, bentonite, pyrophyllite, hectorite, saponite, sauconite, nontronite, talc, beidellite, and volkonskoite. Examples of kaolins include, for example, kaolinite, dickite, nacrite, antigorite, anauxite, halloysite, indellite, and chrysotile. Examples of illites include, for example, bravaisite, muscovite, soda mica, phlogopite, and biotite. Examples of chlorites include, for example, corrensite, magnesian chlorite, donbassite, sutite, magnesian chlorite, and clinochlore. Examples of mixed-layer clays include, for example, allophane and vermiculite biotite. Modifications and isomorphous substitutions of these layered clay minerals impart specific applications.

[0127] Typical gel compositions of the present disclosure include at least one of kaolin and fumed silica. In certain embodiments, including fumed silica can improve the ability of the gel composition to form a substantially horizontal film surface and the ease of removal by peeling of the dried film. The appropriate amount of filler is well known to those skilled in the art and depends on a number of factors, including, for example, the type of polymer(s) filler utilized and the intended treatment area(s) of the gel composition. Typically, the filler can be added at a level of about 1% to about 20% by weight (preferably about 3% to about 15% by weight), or any amount within such a range, based on the total weight of the gel composition. The dried film cast from the gel composition may contain filler in an amount in the range of 0.1% to 30% by weight, or any amount within such a range, based on the total weight of the dried film.

[0128] If bactericidal (or in certain embodiments, bacteriostatic) properties are desired, disinfectants and / or antibiotic formulations may be suspended or otherwise dispersed in the gel composition. In some embodiments, the disinfectant is a cationic antibacterial agent comprising an effective amount of one or more antibacterial agents selected from the group consisting of biguanides and bisbiguanides, such as chlorhexidine, alexidine, and various salts thereof including, but not limited to, digluconate, diacetate, dimethosulfate, and dilactate salts, and combinations thereof; polymeric cationic ammonium compounds such as polyhexamethylene biguanide salts; small molecule quaternary ammonium compounds such as benzalkonium halide; cationic antibacterial dyes; and compatible combinations thereof.

[0129] Particularly useful cationic antibacterial agents include benzalkonium chloride, chlorhexidine gluconate, octenidine dihydrochloride, cetylpyridinium chloride, cetrimonium bromide, benzethonium chloride, polyhexamethylene biguanide salts, methylene blue, toluidine blue, cationic dyes, and compatible combinations thereof. Further details regarding exemplary cationic antibacterial agents can be found in WO 2014 / 008264 pamphlet (Parthasarathy et al.).

[0130] The disinfectant is typically added to the composition at a concentration of at least 0.01 wt%, in some embodiments at least 0.05 wt%, in some embodiments at least 0.1 wt%, in some embodiments at least 0.2 wt%, in some embodiments at least 0.5 wt%, in some embodiments at least 0.6 wt%, in some embodiments at least 1.0 wt%, in still other embodiments at least 1.5 wt%, and in some cases at a concentration exceeding 2 wt%, based on the total weight of the gel composition. Preferably, the composition contains 10 wt% or less, more preferably 8 wt% or less, and most preferably 5 wt% or less. The possible range of disinfectant concentration for improving effective killing is at least 0.1 wt% and 1.0 wt% or less, based on the total weight of the composition. The dried film cast from the gel composition may contain an amount in the range of 0.1 wt% to 4 wt% or any amount within such range of the disinfectant, based on the total weight of the dried film. It should be recognized that the above concentrations relate to the total amount of cationic agents in the composition, even when multiple cationic antibacterial agents are used.

[0131] In certain embodiments, the gel composition may have a synergistic antibacterial effective amount of a disinfectant surfactant, particularly a linear 1,2 -alkanediol having a chain length in the range of 5 to 10 carbon atoms. Such 1,2 -alkanediols include 1,2 -pentanediol, 1,2 -hexanediol, 1,2 -heptanediol, 1,2 -octanediol, 1,2 -nonanediol, and 1,2 -decanediol, and combinations thereof. One exemplary suitable 1,2 -octanediol composition includes 3 -[(2 -ethylhexyl)oxy]-1,2 -propanediol and is sold as SENSIVA SC -10 by Schuelke&Mayr GmbH, Germany. Without wishing to be bound by theory, including the linear 1,2 -alkanediol can reduce the tendency of certain cationic antibacterial agents (e.g., benzethonium chloride) to crystallize in the dried film. By preventing or otherwise reducing the tendency to crystallize, the linear 1,2 -alkanediol can extend the availability of the antibacterial agent in terms of improved effective killing. The dried film cast from the gel composition may contain an amount in the range of 0.5 wt% to 2 wt% of the disinfectant surfactant, or any amount within such range, based on the total weight of the dried film.

[0132] Particularly suitable properties of certain gel compositions containing disinfectants are their ability to reduce the bacterial load on tissues, particularly the skin (e.g., kill the natural skin flora). In certain embodiments, the dried film achieves at least a 1 log reduction of the target microorganisms in 2 hours when evaluated by the antibacterial effect test described below. In more desirable embodiments, the composition achieves a 2 log reduction. In even more desirable embodiments, the composition achieves a 3 log reduction. In certain embodiments, the target organisms include Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, and methicillin-resistant Staphylococcus aureus. In certain embodiments, the remaining antibacterial efficacy is imparted to any surface formed from the dried gel composition. In certain embodiments, the dried film imparts effective killing over a long period during the service life of the film.

[0133] Other anti-infective agents, such as silver nanoparticles and silver sulfadiazine, may also be added to the gel compositions of the present invention. Such anti-infective agents can be added as suspended solids to the coating polymer in a volatile solvent. Topical antibiotics, such as neomycin, polymyxin B, and bacitracin, may also be included. Other solid bioactive materials, such as antipruritics, such as chamomile, eucalyptus, camphor, menthol, zinc oxide, talc, and calamine, anti-inflammatory agents, such as corticosteroids, antifungal agents, such as terbinafine hydrochloride and miconazole nitrate, and non-steroidal anti-inflammatory agents, such as ibuprofen, can be added in a similar manner. Essential oils can also be added as fragrances, flavorants, or antibacterial agents, including thymol, menthol, frankincense, cinnamon, jasmine, lavender, pine, lemon, rose, eucalyptus, clove, orange, mint, spearmint, peppermint, lemongrass, bergamot, citronella, hinoki, nutmeg, cypress, tea tree, wintergreen, and vanilla, and the like. After evaporation of the volatile solvent, the dried film may contain encapsulated active biological or pharmaceutical components for controlled release to the living surface.

[0134] Other exemplary antibacterial agents useful as disinfectants include phenolic disinfectants such as parachlorometaxylenol (PCMX), triclosan, hexachlorophene, and those disclosed in U.S. Patent No. 8,198,326 (Scholz); fatty acid monoesters of glycerin and propylene glycol such as glycerol monolaurate, glycerol monocaprylate, glycerol monocaprate, propylene glycol monolaurate, propylene glycol monocaprylate, propylene glycol monocaprate, C8-C of glycerin and propylene glycol 12 alkyl monoethers such as 2-ethylhexyl glycerin ether (available from Schuelke Mayr, Norderstedt, Germany under the trade name "SENSIVA SC 50"), natural oil disinfectants; C6-C 12 alkyl and aryl carboxylic acids; quaternary silanes, silver, silver salts such as silver chloride, silver oxide, silver sulfadiazine, copper, copper salts, and combinations thereof.

[0135] Other examples of active agents (or drugs) that can be incorporated into the gel compositions of the present disclosure are those that enable topical or systemic effects when administered to the skin. Some examples include buprenorphine, clonidine, diclofenac, estradiol, granisetron, isosorbide dinitrate, levonorgestrel, lidocaine, methylphenidate, nicotine, nitroglycerin, oxybutynin, rivastigmine, rotigotine, scopolamine, selegiline, testosterone, tulobuterol, and fentanyl. Other examples include, but are not limited to, anti-inflammatory drugs both steroidal (e.g., hydrocortisone, prednisolone, triamcinolone) and non-steroidal (e.g., naproxen, piroxicam); bacteriostatic agents (e.g., chlorhexidine, hexylresorcinol); antibacterial agents (e.g., penicillin, e.g., penicillin V, cephalosporin, e.g., cephalexin, erythromycin, tetracycline, gentamicin, sulfathiazole, nitrofurantoin, and quinolone, e.g., norfloxacin, flumequine and ibafloxacin); antiprotozoal agents (e.g., metronidazole); antifungal agents (e.g., nystatin); coronary vasodilators; calcium channel blockers (e.g., nifedipine, diltiazem); bronchodilators (e.g., theophylline, pirbuterol, salmeterol, isoproterenol); enzyme inhibitors, e.g., collagenase inhibitors, protease inhibitors, acetylcholinesterase inhibitors (e.g., donepezil), elastase inhibitors, lipoxygenase inhibitors (e.g., A64077), and angiotensin-converting enzyme inhibitors (e.g., captopril, lisinopril); other antihypertensive agents (e.g., propranolol); leukotriene antagonists (e.g., ICI204,219); anti-ulcer drugs, e.g., H2 antagonists; steroid hormones (e.g., progesterone); antiviral agents and / or immunomodulators (e.g., 1-isobutyl-1H-imidazo[4,5-c]quinolin-4-amine, 1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine, N-[4-(4-amino-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]methanesulfonamide, and acyclovir);Local anesthetics (e.g., benzocaine, propofol, tetracaine, prilocaine); cardiotonics (e.g., digitalis, digoxin); antitussives (e.g., codeine, dextromethorphan); antihistamines (e.g., diphenhydramine, chlorpheniramine, terfenadine); narcotic analgesics (e.g., morphine, fentanyl citrate, sufentanil, hydromorphone hydrochloride); peptide hormones (e.g., human or animal growth hormone, LHRH, parathyroid hormone); cardioactive products, e.g., atrial peptide; antidiabetic agents (e.g., insulin, exenatide); enzymes (e.g., anti-plaque enzymes, lysozyme, dextranase); antiemetics; anticonvulsants (e.g., carbamazepine); immunosuppressants (e.g., cyclosporine); psychotherapeutics (e.g., diazepam); sedatives (e.g., phenobarbital); anticoagulants (e.g., heparin, enoxaparin sodium); analgesics (e.g., acetaminophen, camphor, lidocaine, and others listed in 21 C.F.R 348.10, Analgesic, anesthetic, and antiprunitic active ingredients (April 1, 2012)); anti-migraine agents (e.g., ergotamine, melatonin, sumatriptan, zolmitriptan); antiarrhythmics (e.g., flecainide); antiemetics (e.g., metoclopramide, ondansetron, granisetron hydrochloride); anti-cancer agents (e.g., methotrexate); neuroactive agents, e.g., anxiolytics; anti-obesity agents; dopamine agonists (e.g., apomorphine); GnRH agonists (e.g., leuprolide, goserelin, nafarelin); reproductive hormones (e.g., hCG, hMG, urofollitropin); interferons (e.g., interferon-alpha, interferon-beta, interferon-gamma, PEGylated interferon-alpha); and the like, and pharmaceutically acceptable salts and esters thereof.;

[0136] In an embodiment, an active agent (or drug), for example, by way of example, lidocaine or clobetasol, can be incorporated into the gel composition of the present disclosure. For administration, the gel composition can be applied to the skin and dried to form a film, which can generally be waterproof or water-resistant in an embodiment. The film can be removable, for example, by way of example, similar to a transdermal patch.

[0137] The advantage of such an application is that the film can be less soiled than an ointment or cream and can also act as a barrier or seal to prevent any dirt or bacteria from reaching the skin surface. Further, in an embodiment, the film can be conformable, allowing for application to various locations on the body, including over joints, by way of example. Such a gel composition can be packaged in a manner suitable for multi-purpose or disposable applications.

[0138] In an embodiment, the gel composition includes an active agent (or drug) and at least one penetration enhancer compound. Some examples of suitable penetration enhancer compounds include diethylene glycol monoethyl ether, diisopropyl adipate, dipropylene glycol, ethyl oleate, glyceryl monooleate, isopropyl myristate, isopropyl palmitate, isostearic acid, lauryl lactate, methyl laurate, octyl salicylate, octyldodecanol, oleic acid, oleyl alcohol, oleyl oleate, propylene glycol monolaurate, sorbitan monooleate, and triacetin.

[0139] In an embodiment, the gel composition includes an adhesion promoter, for example, cross-linked, guanidylated polyethyleneimine particles, a silicone polymer, for example, silicone polyoxamide, an active ingredient, for example, lidocaine, and a solvent, for example, hexamethyldisiloxane. The gel composition can further include a silicate tackifying resin and fumed silica.

[0140] In an embodiment, the film (formed after the gel composition has dried) contains an adhesion promoter, such as crosslinked, guanidylated polyethyleneimine particles, a silicone polymer, such as silicone polyoxamide, and an active ingredient, such as lidocaine. In an embodiment, the film may contain lidocaine in an amount between about 1 wt% and about 5 wt% after drying. The film may further contain a silicate tackifying resin and fumed silica.

[0141] The composition may further contain a fiber reinforcement and a colorant, such as a dye, pigment, and lakes. Examples of suitable fiber reinforcements include PGA microfibrils, collagen microfibrils, and others described in U.S. Patent No. 6,183,593. Examples of suitable colorants described in U.S. Patent No. 5,981,621 include 1-hydroxy-4-[4-methylphenylamino]-9,10-anthracenedione (FD&C violet No.2); disodium salt of 6-hydroxy-5-[(4-sulfophenyl)oxo]-2-naphthalenesulfonic acid (FD&C Yellow No.6); 9-(o-carboxyphenyl)-6-hydroxy-2,4,5,7-tetraiodo-3H-xanthen-3-one, disodium salt, monohydrate (FD&C Red No.3); and the like.

[0142] The use of fluorescent dyes and pigments may also be useful in allowing the coating to be visualized under non-visible light. Since the coating can be substantially clear and transparent under normal lighting, the site can be easily visualized and inspected for skin changes. To ensure that the coating is intact and as a means of covering the desired area, the site can be inspected by use of a backlight wand or flashlight that reveals the coating by its fluorescence. A particularly useful hydrocarbon-soluble fluorescent dye is 2,5-bis(5-tert-butyl-2-benzoxazolyl)thiophene. Fluorescent dyes, such as rhodamine, may also be bound to a cationic polymer and incorporated as part of the coagulant.

[0143] Kit The gel compositions of the present disclosure may advantageously be provided in a kit. The kit may contain an applicator, a wound cleansing solution, and an absorbent material. In some embodiments, the gel composition is disposed in the kit in a vial or in another breakable package separate from the applicator. In other embodiments, the applicator has the gel composition pre-loaded therein (e.g., in a delivery reservoir).

[0144] Methods of Application and Removal The treatment protocol may include skin preparation prior to applying the gel compositions of the present disclosure. The target site is preferably dried, for example, by wiping, and then a mildly adhesive polymeric film is formed on the site by applying the gel composition.

[0145] An amount of the composition sufficient to coat (i.e., cover) the entire target site with a layer of the gel composition is used. The resulting dried film typically preferably has a thickness of from about 4 mils (about 0.1016 mm) to about 15 mils (about 0.381 mm). The resulting film typically covers at least the entire area of the wound or other target site, although this may not be the case in other situations. Optionally, excess gel may be removed by wiping fibers or tissue paper prior to drying.

[0146] The gel composition can be applied from a single-dose product or by use of a multiple-use dispenser that regulates the amount of material applied per unit area. In this regard, the dispenser described in U.S. Patent No. 5,558,560 (Benedict) is an example of a dispenser suitable for dispensing a viscous composition through the use of an extrusion tube and an applicator tip. In presently preferred circumstances, the dispenser is suitable for dispensing a gel composition having a viscosity of 200,000 cps (about 200 Pa·s) to 500,000 cps (about 500 Pa·s) (particularly 250,000 cps (about 250 Pa·s) to 400,000 cps (about 400 Pa·s)) and a wet coating weight of 50 mils to 120 mils (about 1.27 mm to about 3.048 mm) with a generally uniform thickness. As other methods for controlled dispensing of the gel composition, by way of example, spray applicators, brushes, wiping fibers, cotton swabs, solid paddle applicators, or applicators for repeated and discontinuous use of the gel composition, and the like can be mentioned. In most applicators (e.g., those featuring a dispensing tip and an extrusion tube), the gel composition can be conveniently stored under ambient conditions and can be provided in a sterile form.

[0147] One suitable method 10 for applying a gel composition to a wound or other target site (e.g., abrasions, lacerations, scratches, punctures, and burns) using an applicator is described in FIG. 1. First, at least the area surrounding the target site is cleaned and dried (step 20). Due to the conformability and breathability of the dried film of the present disclosure, drying of the wound itself may be optional depending on the amount of fluid exiting the wound site. In certain embodiments, the dried film can hold up to 1 mL of blood or exudate without being pulled away from the body. In moderately to severely bleeding wounds, the site is typically cleaned and dried prior to application. An initial amount of the gel composition in the applicator 12 is dispensed in the proximal region of the target site 11, and a substantially continuous layer 13 of the gel composition is created by pulling the applicator across the target site 11 while dispensing the composition from the tip 14 (step 30). In certain situations, it may be desirable to hold the applicator tip 14 above the target site without contacting the tissue. Such a vertical replacement may not be required for small scratches or skin lesions. Once the layer 13 reaches the proximal region of the target site (e.g., where there is space from the wound), the applicator is manipulated to sever the connection between the layer 13 and the applicator tip (step 40). The user may also sever this connection by hand or other tool. In certain implementations, the layer 13 has dimensions sufficient to completely cover the target site. However, for larger wounds or smaller applicator tips, multiple layers may be used. In one exemplary implementation, the continuous layer 13, when applied, has a substantially continuous thickness of about 100 mils (about 2.54 mm). Once the desired amount of gel is dispensed, the composition is dried to form a film (typically 2 - 5 minutes).

[0148] Another suitable method for applying a gel composition to a target site using an applicator is described in FIG. 2. Similar to method 10 of FIG. 1, method 100 of FIG. 2 includes: a) a step of cleaning and drying at least the area around the target site (step 120); dispensing an initial amount of the gel composition in the area proximal to the target site 110 and pulling the applicator across the target site 110 while dispensing the composition to create a substantially continuous layer 113 of the gel composition (step 130), and a step of severing the connection between the layer 113 and the applicator tip 114 (step 140). After a period sufficient for the composition to dry to form a touchable film 115 (typically 1-2 minutes), the user (or treatment professional) can tap the film around the outer edge of the target to seal around the target and improve this (step 150). In some embodiments, it may be desirable for the person touching the film to first wet their finger. Alternatively, the user (or treatment professional) can wet the surface of the finger with a topical disinfectant or antibiotic composition to increase protection against infection or contamination. Instead of finger pressure, a surface pressing tool, such as a Q-tip, tongue depressor, and foam applicator, may be used.

[0149] One such tool is used in method 200 shown in FIG. 3. Similar to method 100 of FIG. 2, method 200 includes: a) a step of cleaning and drying at least the area around the target site (step 220); dispensing an initial amount of the gel composition in the area proximal to the target site 210 and pulling the applicator 212 across the target site 210 while dispensing the composition to create a substantially continuous layer 213 of the gel composition (step 230), and a step of severing the connection between the layer 213 and the applicator tip 214 (step 240). The applicator tip 214 includes a convex surface 218 adjacent to the dispensing slot. Instead of finger pressure, the user (or treatment professional) can use the convex surface 218 of the applicator to tap the film around the outer edge (step 250). Using the applicator tip in this way can be advantageous because for certain users and types of wounds, use with the perceived (or actual) contamination of their fingers can be eliminated.

[0150] Applicator tips suitable for applying pressure to a gel composition or film are shown in FIGS. 4 and 5. Each applicator tip 214 includes a generally frustoconical body 215 having a dispensing slot 216 positioned (oriented) toward the top of the tip 214. The dispensing slot 216 is sized to dispense a gel composition having a viscosity of 200,000 to 400,000 cps (about 200 to about 400 Pa·s) and a wet coating weight of 50 to 120 mils (about 1.27 to about 3.048 mm) with a generally uniform thickness. The dispensing slot 216 can be installed at an acute or obtuse angle with respect to the plane defined by the bottommost surface of the body 214. In other embodiments, the dispensing slot can be generally parallel to the plane defined by the bottommost surface of the body 214. The raised portion 217 projects outward from the body 215, shifting the surface 218 away from the body 215. The shifted outer surface 218 allows the applicator tip 214 to be pressed against the gel composition or film without contacting the dispensing slot 215. The outer surface 218 can include a lens-like convex structure (FIG. 4) or a rail-like planar structure (FIG. 5). Those skilled in the art will recognize that other geometries and configurations are possible for the surface 218 as well as the applicator tip body 215. The applicator tip 214 can be supplied with or without a cap 219 used to cover the dispensing slot when the applicator is not in use.

[0151] Another suitable method 300 for applying the gel composition of the present disclosure to a target site is disclosed in FIG. 6. At least the region surrounding the target is also dried, but the substantially continuous layer 313 is not drawn over the target. Instead, in step 330, an initial amount of the gel composition is dispensed in the region proximal to the target site 311, and a substantially continuous layer 313 of the gel composition is created by pulling an applicator along the outer edge of the target site 311 while dispensing the composition from the tip 314. After severing the connection between the layer and the applicator (step 340), the resulting layer 313 is drawn across the target site and pressed on the side of the target site opposite the original location of the layer 313 (step 350). The composition can be drawn by hand (as shown) or by a suitable tool.

[0152] The gel composition need not be applied in direct contact with the entire target site. In certain embodiments, the gel composition may be applied over a disinfectant or antimicrobial composition, a suture, a gauze, other topical compositions, and combinations thereof.

[0153] As mentioned above, the applied gel composition of the present disclosure can be removed with relatively little force in a single continuous film without substantial exfoliation of the underlying tissue. This desired property can be improved by rolling the edges of the applied film towards the center of the target (or the film itself) prior to removal. By rolling, in certain situations, an edge can be provided that allows a user or treatment professional to grip and pull the film off the skin. For thinner films (e.g., less than 4 mils (less than about 0.1016 mm)), it may be sufficient for the film to be removed in multiple pieces.

[0154] The objects and advantages of this disclosure are further illustrated in the following examples, but the specific materials and their amounts, as well as other conditions and details recited in these examples, should not be construed as unduly limiting this disclosure.

Examples

[0155] Materials Used in the Examples

Table 1

[0156] Test method Test method A: In vitro penetration using human cadaver skin (HCS) The in vitro penetration study was conducted using a Franz diffusion cell, human cadaver skin (HCS), and a receptor solution to investigate the drug diffusion characteristics of different compositions across the skin. In the lidocaine penetration study, the receptor solution consisted of an aqueous phosphate buffered saline solution at pH 7.4 containing 0.005% gentamicin added for microbial control. In the clobetasol propionate ester penetration study, the receptor solution was an 80 / 20 v / v blend of an aqueous phosphate buffered saline solution at pH 7.4 containing 0.004% gentamicin added for microbial control and polyethylene glycol 400.

[0157] The adhesive patch formulation of Comparative Example A was prepared as a rollstock consisting of a patch formulation sandwiched between a backing film and release paper. For each study, individual 1 cm 2 patch samples were punched out from the rollstock to be examined in 4 or 5 replicates. The release paper was removed, the patch sample was pressed onto the stratum corneum of the HCS, clamped in a Franz diffusion cell, and oriented with the donor chamber side of the diffusion cell. 2 For the gel compositions of the present invention (EX1 to EX16), approximately 0.2 mL of the gel was dispensed onto the HCS using a 1 mL syringe. The gel composition was then spread over a 1 cm

[0158] The receptor chamber of the cell contained 5 - 6 mL of the receptor solution and a magnetic stir bar. The sampling port opening in the receptor chamber was covered with parafilm to prevent evaporation of the receptor solution. Any air bubbles trapped in the receptor chamber were allowed to escape into the empty portion of the sampling port to ensure complete contact between the receptor solution and the HCS throughout the study.

[0159] Each Franz cell was placed in a temperature-controlled permeation chamber having a capacity to hold 48 cells. The chamber was controlled to 32 °C (about 305.15 K) ± 1 °C (about 274.15 K) with ambient humidity. The receptor solution was continuously mixed using a magnetic stir bar in the receptor chamber of the cell. At each sampling time point, the volume of the total receptor solution was transferred to a properly sized Luer lock syringe equipped with a 0.45 micron PTFE filter. The solution was then filtered, transferred to an HPLC vial, sealed, and analyzed for drug content. At intermediate sampling time points, the receptor chamber of each cell was immediately refilled with receptor solution, and the cell was returned to the chamber and placed there. The results of the drug content of the receptor solution were used to quantify the reflux and / or cumulative delivery of lidocaine or clobetasol propionate over the duration of the study. Sections of HCS from each diffusion cell were also placed in vials and analyzed for drug concentration localized in the skin.

[0160] The integrity of each skin piece was described and considered in the analysis of the permeation data. Data showing unusually high delivery that could be related to the integrity of the skin sample were removed from the analysis to avoid reporting spuriously high delivery values.

[0161] Test method B: HPLC method for clobetasol propionate in receptor solution and skin samples Receptor solution samples from the HCS permeation study were analyzed for clobetasol propionate content using an Agilent 1200 HPLC equipped with a UV detector. An Agilent Eclipse XDB-C18 column (particle size 3.5 mcm, diameter 2.1 mm × length 150 mm) maintained at 40 °C (about 313.15 K) was used as the stationary phase. A gradient mobile phase of water and acetonitrile was used. The gradient parameters were as follows.

[0162] [Table 2]

[0163] The mobile phase flow rate was 0.4 mL / min. A 100 microliter injection was prepared from the filtered receptor solution sample. UV detection was performed at a wavelength of 240 nm. The approximate retention time was 7.63 minutes and the run time for each sample was 16 minutes.

[0164] After completion of the HCS penetration study, each skin sample was placed in a separate 20 mL vial and 2 mL of 1% trifluoroacetic acid in methanol was added as the extraction solvent. The vial was placed on a reciprocating shaker at approximately 150 strokes / min for approximately 60 hours. The extraction solvent was then drawn into a syringe and filtered into a standard HPLC vial through a 0.45 micron Aerodisc PTFE filter. The clobetasol propionate content of the filtered extract was then determined using the same HPLC method as used for the receptor solution samples.

[0165] Test method C: HPLC method for lidocaine in receptor solution and skin samples Receptor solution samples from the HCS penetration study of lidocaine were analyzed using an Agilent 1200 HPLC equipped with a UV detector. A Zorbax Extend C-18 column (particle size 3.6 microns, diameter 4.6 mm x length 75 mm) maintained at 40 °C (approx. 313.15 K) was used as the stationary phase. The isocratic mobile phase was prepared by mixing 2587 mL of water, 12.94 mL of 5N ammonium hydroxide, 700 mL of methanol, and 700 mL of isopropanol. The mobile phase flow rate was 0.5 mL / min. A 15 microliter injection was prepared from the filtered receptor solution sample. UV detection was performed at a wavelength of 254 nm. The approximate retention time was 4.09 minutes and the run time for each sample was 10 minutes.

[0166] After the HCS penetration study was completed, each skin sample was placed into a separate 20 mL vial, and 2 mL of 1% trifluoroacetic acid in methanol was added as the extraction solvent. The vial was placed on a reciprocating shaker at approximately 200 movements per minute for approximately 60 hours. The extraction solvent was then drawn up into a syringe and filtered into a standard HPLC vial through a 0.45 micron Aerodisc PTFE filter. The lidocaine content of the filtered extract was then determined using an Agilent 1200 HPLC equipped with a UV detector. A Zorbax Extend C-18 column (particle size of 3.6 microns, diameter 4.6 mm x length 75 mm) maintained at 25 °C (approximately 298.15 K) was used as the stationary phase. The isocratic mobile phase was prepared by mixing 2587 mL of water, 12.94 mL of 5N ammonium hydroxide, 700 mL of methanol, and 700 mL of isopropanol. The mobile phase flow rate was 1.3 mL / min. A 15 microliter injection was made from the skin extract sample. UV detection was performed at a wavelength of 230 nm. The approximate retention time was 7.65 minutes, and the run time for each sample was 12 minutes.

[0167] Examples 1 - 16 Gel compositions (EX1 - EX16) To facilitate the suspension of the insoluble particles, g-PEI was ground into a fine powder using a mortar and pestle. The gel compositions (EX1 - EX16) were prepared according to the following method: Into a glass vial of appropriate size (25 g), the components of additive group 1 (solvent vehicle HMDS and ethyl acetate) were added, followed by the components of additive group 2. A magnetic stir bar was then placed in each vial, and the vial was closed with a sealed cap. Each vial was placed on a hot plate with temperature control set at 65 °C (about 338.15 K) to 70 °C (about 343.15 K) (by rapid stirring). Once a clear solution was obtained, finely ground g-PEI particles (additive group 3) were added to the suspension. Rapid stirring and heating were continued to facilitate a uniform suspension of the g-PEI particles. Then, SPOx (additive group 4) was added to the hot suspension, and the mixture was held at 65 °C (about 338.15 K) to 70 °C (about 343.15 K) for about 3 to 6 hours (by stirring). Each composition was completed when all visible polymers were completely dissolved. The components of additive groups 1 to 4 are confirmed in Tables 1 to 4.

[0168]

Table 3

[0169]

Table 4

[0170]

Table 5

[0171]

Table 6

[0172] Lidocaine-containing adhesive patch (Comparative Example A) A lidocaine-containing adhesive patch was prepared by adding 0.3571 g of lidocaine, 0.3723 g of isopropyl myristate, 0.3880 g of oleyl alcohol, and 18.6287 g of a solvated acrylate adhesive to a glass bottle of suitable volume. The solvated acrylate adhesive was a copolymer consisting of 93 parts of isooctyl acrylate and 7 parts of acrylamide in a 32% solids ethyl acetate / methanol (approximately 90 / 10) solvent mixture. The glass bottle containing the solvated lidocaine / excipient / adhesive mixture was placed on a bottle roller and mixed for approximately 12 hours. The solution was then coated onto Scotchpak 9744 release paper (3M Company) using a flatbed knife coater having a coating gap of 0.018 inches (approximately 0.05 cm). The coated release paper was then placed in a drying oven at 109°F (approximately 42.78°C, approximately 315.93 K) for 10 minutes, removed from the oven, and laminated to CoTran 9722 backing film (3M Company). 1 cm 2 circular punches were then used to cut patches for penetration studies.

[0173] Example A. Delivery of Lidocaine over Time Two gel composition samples containing lidocaine (EX1 and EX2) were individually tested and compared to a lidocaine-containing adhesive patch (Comparative Example A) using Test Method A (in vitro penetration using HCS). The total volume of the receptor solution was collected for analysis at 3 hours, 9 hours, and 24 hours. At each time point, fresh receptor solution was added to the Franz cell. The lidocaine content in the skin sample was evaluated at 24 hours. The amount of lidocaine was quantified from both the receptor solution and the skin sample using Test Method C. The results are summarized in Table 5. At the 3-hour time point, gel compositions EX1 and EX2 showed more lidocaine penetration compared to the adhesive patch sample (Comparative Example A).

[0174]

Table 7

[0175] Example B. 24-Hour Clobetasol Delivery Gel compositions containing clobetasol propionate (EX3 - EX16) were evaluated using Test Method A (in vitro penetration using HCS). The total volume of the receptor solution and skin samples were collected for analysis over 24 hours. Test Method B (HPLC method for clobetasol) was used to quantify clobetasol propionate in the receptor solution and skin samples. The results are summarized in Tables 6 and 7. Each table includes data from the execution of individual experiments.

[0176] [Table 8]

[0177] [Table 9]

[0178] Example C. In vivo Delivery of Lidocaine Studies in minipigs were conducted to evaluate pharmacokinetics and tolerability. The studies were approved by 3M's Institutional Animal Care and Use Committee, and the care of the animals was in accordance with all applicable national and local regulations.

[0179] The gel compositions were generally prepared as described in Example 1. The comparative test article was prepared by die-cutting a 15 cm patch from a Lidoderm (trademark) patch (Endo Pharmaceuticals, Malvern, PA). 2 The patch was prepared by die-cutting.

[0180] The studies were conducted in five 8 - 9-month-old Göttingen minipigs. A two-way crossover design was used for each minipig receiving each treatment. The animals were anesthetized and the dosing area, consisting of three 4 cm × 4 cm areas on the back, was shaved prior to application. The comparative treatment was three 15 cm patches applied to the dosing area for 24 hours. 2Consisted of patches (total nominal dosage of 225 mg), i.e., one patch per 4 cm × 4 cm area. The test treatment consisted of approximately 3 mL of gel composition applied to each 4 cm × 4 cm area (total nominal dosage of 81 mg). The minimum washout time between treatment dosages to ensure that blood plasma levels returned to zero was 48 hours. Blood plasma was collected at 0, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 24 hours, 26 hours, 28 hours, and 48 hours after dosing. Erythema and edema were measured using a 0 - 4 scale where 0 indicates no effect and 4 indicates severe effect, respectively, and were observed at patch removal and 24 hours after removal. Plasma was analyzed using the standard HPLC method.

[0181] The test article caused minimal erythema and edema at removal and 24 hours after removal. The lidocaine plasma concentrations of the test and comparative articles are shown in Table 8.

[0182]

Table 10

[0183] The complete disclosure contents of the patents, patent documents, and published gazettes listed in this specification are incorporated by reference in their entirety as if each were individually incorporated. Various modifications and alterations of the present invention will be apparent to those skilled in the art without departing from the scope and spirit of the present invention. It is not intended that the present invention be unduly limited by the exemplary embodiments and examples described herein, and such examples and embodiments are presented by way of illustration only as being limited only by the scope of the claims described herein as follows, and it should be understood that the scope of the present invention is intended to be so limited.

Claims

1. A gel composition for use as a conformable film dressing, comprising: a silicone-containing film-forming polymer; an amine-rich adhesion promoter; a volatile solvent; and an active ingredient wherein the film cast from said gel composition is self-supporting in a biological substrate and can be peeled off from said substrate, said gel composition.

2. The gel composition according to claim 1, further comprising a penetration enhancer.

3. The gel composition according to claim 2, wherein said penetration enhancer is selected from the group consisting of diethylene glycol monoethyl ether, diisopropyl adipate, dipropylene glycol, ethyl oleate, glyceryl monooleate, isopropyl myristate, isopropyl palmitate, isostearic acid, lauryl lactate, methyl laurate, octyl salicylate, octyldodecanol, oleic acid, oleyl alcohol, oleyl oleate, propylene glycol monolaurate, sorbitan monooleate, triacetin, and any combination thereof.

4. The gel composition according to claim 1, wherein said active ingredient comprises lidocaine.

5. The gel composition according to claim 2, wherein said active ingredient comprises lidocaine.

6. The gel composition according to claim 3, wherein said active ingredient comprises lidocaine.

7. A self-supporting film cast from the composition according to claim 4, wherein said lidocaine is present in an amount between about 1 wt% and about 5 wt%.

8. A self-supporting film cast from the composition according to claim 5, wherein said lidocaine is present in an amount between about 1 wt% and about 5 wt%.

9. A self-supporting film cast from the composition according to claim 6, wherein said lidocaine is present in an amount between about 1 wt% and about 5 wt%.

10. A gel composition for use as a conformable film dressing, comprising: a silicone-containing film-forming polymer; an amine-rich adhesion promoter; a volatile solvent; a penetration enhancer; and lidocaine wherein said gel composition.

11. A film-forming gel composition for use as a conformable film dressing, comprising: a silicone-containing polymer; an adhesion promoter comprising a silicate tackifying resin; a coagulant comprising a cationic polymer; and a volatile solvent A gel composition comprising a film cast from the composition, the film being self-supporting on a biological substrate and capable of being peeled from the substrate without substantially impairing the integrity of the film or the substrate.

12. A conformable film dressing comprising: A silicone-containing film-forming polymer; An amine-rich adhesion promoter; A volatile solvent; A penetration enhancer; and Lidocaine The conformable film dressing comprising the above.

13. A gel composition for use as a conformable film dressing comprising: A silicone-containing film-forming polymer; An amine-rich adhesion promoter; A volatile solvent; and An active ingredient A gel composition comprising a film cast from the gel composition, the film being self-supporting on a biological substrate and capable of being peeled from the substrate.

14. The gel composition according to claim 13, further comprising a penetration enhancer.

15. The penetration enhancer is selected from the group consisting of diethylene glycol monoethyl ether, diisopropyl adipate, dipropylene glycol, ethyl oleate, glyceryl monooleate, isopropyl myristate, isopropyl palmitate, isostearic acid, lauryl lactate, methyl laurate, octyl salicylate, octyldodecanol, oleic acid, oleyl alcohol, oleyl oleate, propylene glycol monolaurate, sorbitan monooleate, triacetin, and any combination thereof; The gel composition according to claim 14.

16. The gel composition according to claim 13, wherein the active ingredient comprises lidocaine.

17. The gel composition according to claim 14, wherein the active ingredient comprises lidocaine.

18. The gel composition according to claim 15, wherein the active ingredient comprises lidocaine.

19. A self-supporting film cast from the composition according to claim 16, wherein the lidocaine is present in an amount between about 1 wt% and about 5 wt%.

20. A self-supporting film cast from the composition according to claim 17, wherein the lidocaine is present in an amount between about 1 wt% and about 5 wt%.

21. A self-supporting film cast from the composition according to claim 18, wherein the lidocaine is present in an amount between about 1 wt% and about 5 wt%.

22. A gel composition for use as a conformable film dressing comprising: A silicone-containing film-forming polymer; An amine-rich adhesion promoter; A volatile solvent; A penetration enhancer; and Lidocaine The gel composition comprising the same.

23. A film-forming gel composition for use as a conformable film dressing, comprising: A silicone-containing polymer; An tackifier comprising a silicate tackifying resin; A coagulant comprising a cationic polymer; and A volatile solvent The gel composition, wherein a film cast from the composition is self-supporting on a biological substrate and can be peeled from the substrate without substantially impairing the integrity of the film or the substrate.

24. A conformable film dressing, comprising: A silicone-containing film-forming polymer; An amine-rich adhesion promoter; A volatile solvent; A penetration enhancer; and Lidocaine The conformable film dressing comprising the same.

Images