Novel antimicrobial compositions and articles made therefrom

Abstract

Antimicrobial compositions and articles, and methods for preparing the antimicrobial compositions are disclosed. Methods of using the antimicrobial compositions and articles to prevent the formation or growth of biofilms, disrupt biofilms, reduce microbial counts, and treat infections are also disclosed.

Description

[Background technology]

[0001] Despite advances made in infection control practices, surgical site infections (SSIs) remain a substantial cause of morbidity, extended hospital stays, and mortality. In fact, SSIs are associated with 3% of mortality rates, and 75% of SSI-related deaths are directly attributable to SSIs. Surgeons currently rely on surgical drapes with iodine-impregnated adhesives to mitigate contact with pathogenic microorganisms. Although povidone-iodine is a widely effective disinfectant, its use has drawbacks. For example, povidone-iodine can cause skin irritation in some individuals, and use in large wounds can result in kidney problems, high blood sodium, and metabolic acidosis. Furthermore, the use of povidone-iodine is not recommended for those less than 32 weeks pregnant, those prescribed lithium, or those with thyroid problems. Chlorhexidine gluconate and octenidine hydrochloride are viable alternatives that are not associated with the aforementioned fallbacks.

[0002] Developing an antiseptic-impregnated adhesive (e.g., an adhesive impregnated with chlorhexidine gluconate and octenidine hydrochloride) would help reduce surgical site infection rates while potentially avoiding the side effects associated with povidone-iodine. What is needed is a pressure-sensitive adhesive that can carry and deliver chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof. Summary of the Invention

[0003] In one embodiment, a composition is described. The composition comprises chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof, and a hydrophobic plasticizer capable of solubilizing chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof, in an amount of at least about 2 g of chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof per 100 g of hydrophobic plasticizer at a temperature of about 20-23° C. The hydrophobic plasticizer has at least two hydrogen bonding groups separated by more than three consecutive atoms and is characterized by an HLB of 10 or less as determined using the HLB method.

[0004] In one embodiment, an antimicrobial adhesive is described. The antimicrobial adhesive comprises any of the compositions and pressure sensitive adhesives described herein.

[0005] In one embodiment, a medical article is described. The medical article includes a substrate and any of the antimicrobial adhesives described herein disposed on the substrate.

[0006] In one embodiment, a method for preparing the compositions described herein is described, comprising providing chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof and a hydrophobic plasticizer, and contacting the chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof with the hydrophobic plasticizer to form the composition.

[0007] In one embodiment, a method for preparing the antimicrobial adhesive described herein is described, the method comprising providing a composition and a pressure sensitive adhesive described herein, and contacting the composition with the pressure sensitive adhesive to form the antimicrobial adhesive.

[0008] In one embodiment, a method for preparing a medical article as described herein is described, the method comprising providing an antimicrobial adhesive and a substrate as described herein, and coating the antimicrobial adhesive onto the substrate.

[0009] In one embodiment, a method for disinfecting a surface is described that includes providing a medical article as described herein and contacting the medical article with the surface for a period of time.

[0010] In one embodiment, a method for preparing a surface for surgery is described. The method may include providing a medical article as described herein and contacting the medical article with a surface.

[0011] In one embodiment, a kit is described that includes a medical article as described herein and a set of instructions instructing a user to disinfect a surface according to the methods described herein. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] Efforts to develop preservative-impregnated adhesives face significant challenges. Chlorhexidine gluconate ("CHG") and octenidine hydrochloride ("octenidine"), respectively, are highly polar compounds that tend to precipitate from hydrophobic adhesive compositions. Lack of CHG solubility or octenidine solubility in the adhesive effectively immobilizes the CHG or octenidine so that they are not available for adequate migration to the surface. Furthermore, blending additives such as CHG and CHG solubilizing vehicles often compromises the strength of the adhesive, leading to premature adhesive failure. In the context of surgical drapes, this premature adhesive failure is referred to as "drape drift." When surgical drapes move or "drift," patients experience greater exposure to microorganisms and become more vulnerable to infection.

[0013] The present disclosure is directed to chlorhexidine gluconate-based and octenidine hydrochloride-based compositions for inclusion in pressure-sensitive adhesive (PSA) formulations in a homogeneous manner, and medical articles made therefrom.Initially, it was believed that a hydrophilic (polar) vehicle was necessary to make chlorhexidine gluconate or octenidine hydrochloride compatible with adhesives.Later, it was found that a hydrophobic (non-polar) vehicle with vicinal (i.e., separated by two atoms; adjacent) or otherwise proximate (i.e., separated by three atoms) hydrogen bonding groups is effective in solubilizing chlorhexidine gluconate and octenidine hydrochloride, which in turn makes hydrophobic CHG and octenidine solutions compatible with hydrophobic pressure-sensitive adhesives (see WO2014 / 035981). In this study, it is surprisingly found that CHG and octenidine, although polar compounds, are easily dissolved in hydrophobic plasticizers with hydrogen bonding groups that are more than 3 atoms apart.In addition, it is surprisingly found that hydrophobic vehicles with nearby hydrogen bonding groups can be detrimental to adhesive integrity compared to compositions that do not contain said hydrophobic vehicles.The long-sought means for incorporating CHG and / or octenidine hydrochloride into PSA-containing medical articles, such as surgical drapes, is presented herein.

[0014] As used herein, "about" means plus or minus ten percent of a given value. For example, about ten means from nine to eleven.

[0015] As used herein, "acid" refers to a carboxylic acid group, i.e., -CO2H.

[0016] As used herein, "alkyl" refers to a straight-chain or branched saturated hydrocarbon group. 1~6 "Alkyl" refers to the number of carbon atoms in the hydrocarbon group. For example, C 1~6means 1 to 6 carbons, e.g., methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, pentyl, hexyl, and the like.

[0017] As used herein, "alkyl diol" refers to a linear or branched saturated hydrocarbon group having two hydroxyl (-OH) groups. For example, C5 alkyl 1,2-diol means CH3CH2CH2CH(OH)CH2(OH), CH3CH(CH3)CH(OH)CH2(OH), etc. For example, C5 alkyl 1,3-diol means CH3CH2CH(OH)CH2CH2(OH), etc. "Alkyl triol" refers to a linear or branched saturated hydrocarbon group having three hydroxyl (-OH) groups.

[0018] As used herein, "alkylene" refers to a straight or branched divalent hydrocarbon group. For example, C alkylene refers to -CHCHCHCHCHCHCHCH-, -CHCH(CHCH)CHCH-, and the like.

[0019] As used herein, "alkenyl" refers to a straight-chain or branched unsaturated hydrocarbon group. For example, C4 alkenyl refers to -CH2=CHCH2CH3, -CH2=C(CH3)CH3, -CH2=CHCH2=CH2, etc.

[0020] As used herein, "alkenylene" refers to a straight or branched divalent unsaturated hydrocarbon group. For example, C4 alkenylene refers to -CH2=CHCH2CH2-, -CH2=C(CH3)CH2, -CH2=CHCH2=CH-, etc.

[0021] As used herein, "consecutive atoms" refers to atoms (e.g., carbon, nitrogen, oxygen, and sulfur) that are linked together to form a chain. Groups separated by several consecutive atoms mean that the chain includes that number of intervening atom groups. For example, the hydroxyls in the following chain are separated by four consecutive atoms: HOCH2CH2CH(CH3)CH2OH, HOCH2CH=CHCH2OH, HOCH2C(O)CH2CH2OH, etc.

[0022] As used herein, "cyclohexylene" refers to a divalent six-membered cyclic hydrocarbon group.

[0023] As used herein, "cyclohexenylene" refers to a divalent 6-membered cyclic hydrocarbon group having one or more units of unsaturation, i.e., -C(R)=C(R)-.

[0024] As used herein, "excluded" means that 0.0% by weight of a substance is present in the composition.

[0025] As used herein, "derived" means that a component X can be prepared from a compound Y, e.g., a hydrophobic plasticizer (X) is C 16~44 This means that it can be prepared (derived) from an alkyl acid compound (Y). One of skill in the art will readily recognize suitable synthetic methods for reacting any of the compounds Y described herein. For example, one of skill in the art will recognize suitable synthetic methods for reacting any of the compounds Y described herein. a CO2H,R a is optional) and alcohol (R b -OH, R b is optional) to form an ester (R a CO2R b ) can be formed.

[0026] As used herein, "disinfection" refers to the reduction in the number of active microorganisms present on the surface being disinfected. Disinfection may kill the microorganisms or prevent them from growing or multiplying.

[0027] As used herein, a "hydrogen bonding group" refers to a group having a lone pair of electrons and an atom with greater electronegativity than carbon. An atom of such characterization may bond with a hydrogen atom bonded to another such group by a process known in the art as hydrogen bonding. For example, -OH, -NH2 and -SH, -O-, -N(CH3)- and -S- are all considered hydrogen bonding groups.

[0028] As used herein, "hydrogen bond donor" refers to a hydrogen bonding group that comprises a hydrogen atom bonded to an atom having a lone pair of electrons. For example, -OH, -NH2, and -SH are hydrogen bond donors.

[0029] As used herein, the "hydrophilic lipophilic balance" or "HLB" value is calculated using the method of Griffin (Griffin WC; J. Soc. of Cosmetic Chemists 5, 259 (1954)). Thus, as used herein, the "HLB method" refers to a calculation based on:

number

[0030] As used herein, "hydrophilic vehicle" refers to a compound characterized by an HLB value of greater than 10. The hydrophilic vehicle described by this disclosure is intended to include compounds having a molecular weight of 5 kg / mole or less. Furthermore, the hydrophilic vehicle described by this disclosure is not intended to include water.

[0031] As used herein, "hydrophobic vehicle" refers to a compound characterized by an HLB value of 10 or less and having two hydrogen bonding groups (e.g., alkoxy, e.g., R-CH(X)CH(X), R-X-CHCHX, etc., separated by three or fewer atoms.

[0032] As used herein, "hydroxyl number" refers to a measure of the content of free hydroxyl groups in a chemical, expressed in units of the mass of potassium hydroxide in milligrams equivalent to the hydroxyl content of one gram of the chemical.

[0033] As used herein, "optionally substituted" refers to a chemical entity or group that may or may not be substituted with one or more described chemical moieties. For example, "C optionally substituted with one or more hydroxyl" refers to a 1~6 "Alkyl group" refers to an unsubstituted C 1~6 C substituted with alkyl group or one or more -OH 1~6 Alkyl groups are intended to be included, such as, for example, 2-hydroxybutyl.

[0034] As used herein, "plasticizer" refers to a substance or combination of substances that lowers the glass transition temperature of another substance (e.g., a pressure sensitive adhesive). A plasticizer effectively softens, increases flexibility, increases plasticity, decreases viscosity, and / or decreases friction of the substance to which it is added. The plasticizers described herein are relatively low molecular weight polymers that increase the spacing between chains of a larger molecular weight polymer (i.e., a PSA).

[0035] As used herein, "polymer" refers to a material having one or more repeating monomeric units. The chemical identity of a polymeric material herein may be described in terms of the monomers from which the polymer is derived. Those skilled in the art will readily understand the reactivity profile of the listed monomers and how the monomers may be synthetically combined to form a polymer.

[0036] As used herein, "pressure sensitive adhesive" refers to a non-reactive self-adhesive adhesive that forms a bond when pressure is applied. No solvents, water, or heat are required to activate a pressure sensitive adhesive.

[0037] As used herein, "substituted" means the replacement of any present C-H bond with the reported substituent (X), i.e., CH→CX.

[0038] When referring to "solubility" or "solubilizing," it should be understood that the solubility of component A in component B refers to the condition where only components A and B are present, e.g., no added salts, compounds, etc. Additionally, any solubility values ​​provided herein relate to a temperature range of about 20° C. to about 23° C. at atmospheric pressure (i.e., 760 mm / Hg).

[0039] As used herein, "unsaturated" means that the substance contains a unit of unsaturation, i.e., two adjacent hydrogens have been removed to form a pi bond between the atoms. Unsaturated units include alkenes (-C(R)=C(R)-) and alkynes (-C≡C-).

[0040] It is to be understood that any generalized chemical name is intended to include only those chemical groups that are listed in the generalized chemical name, e.g., substituted, optionally substituted, etc., unless specifically stated otherwise. For example, C 18 Alkyl acids are C 18It consists of an alkyl group and a carboxylic acid group. For example, C 18 Alkyl acids are C 18 It consists of an alkyl group, a carboxylic acid group, and one or more hydroxyl substitutions.

[0041] composition In various embodiments, compositions are described. The compositions may include chlorhexidine gluconate and / or octenidine hydrochloride and a hydrophobic plasticizer capable of solubilizing chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof, in an amount of at least about 2 g of chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof per 100 g of hydrophobic plasticizer at a temperature of about 20-23° C. The hydrophobic plasticizer may include at least two hydrogen bonding groups separated by more than three consecutive atoms and may be characterized by an HLB of 10 or less as determined using the HLB method.

[0042] In some embodiments, the composition may consist essentially of chlorhexidine gluconate, octenidine hydrochloride, and a hydrophobic plasticizer. In some embodiments, the composition may consist essentially of chlorhexidine gluconate, and a hydrophobic plasticizer. In some embodiments, the composition may consist essentially of octenidine hydrochloride, and a hydrophobic plasticizer.

[0043] In some embodiments, the composition may comprise chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof present in an amount of at least about 0.05% by weight of the composition, In some embodiments, the composition may comprise chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof present in an amount of about 5% by weight or less by weight of the composition. The composition may comprise chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof present in an amount of about 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.2, 1.4, 1.6, 1.8, 2.0, 2.2, 2.4, 2.6, 2.8, 3.0, 3.2, 3.4, 3.6, 3.8, 4.0, 4.2, 4.4, 4.6, 4.8, 5.0% by weight (by weight of the composition), or a range of values ​​between any of the aforesaid values, such as, for example, about 0.2% to about 4.0% by weight, about 2.0% to about 3.0% by weight, etc.

[0044] In some embodiments, the composition may include chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof present in an amount of at least about 0.1% by weight relative to the weight of the hydrophobic plasticizer. In some embodiments, the composition may include chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof present in an amount of about 20% by weight or less relative to the weight of the hydrophobic plasticizer. The composition may include chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof present in an amount of about 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, or 20% by weight (relative to the weight of the hydrophobic plasticizer), or a range of values ​​between any of the foregoing values, such as about 0.5% to about 12% by weight, about 1% to about 10% by weight, etc.

[0045] In some embodiments, the composition may include a hydrophobic plasticizer present in an amount of at least about 10% by weight based on the weight of the composition. In some embodiments, the composition may include a hydrophobic plasticizer present in an amount of about 50% by weight or less based on the weight of the composition. The composition may include a hydrophobic plasticizer present in an amount of about 10, 15, 20, 25, 30, 35, 40, 45, or 50% by weight (based on the weight of the composition), or a range of values ​​between any of the foregoing values, such as about 10% to about 25% by weight, about 20% to about 40% by weight, etc.

[0046] In some embodiments, the composition may further comprise water present in an amount of less than about 1% by weight based on the weight of the composition. In some embodiments, the composition may further comprise water present in an amount of about 0, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0% by weight (based on the weight of the composition), or a range of values ​​between any of the foregoing values, such as about 0.01% to about 1% by weight, about 0.1% to about 0.5% by weight, etc.

[0047] In some embodiments, the composition may further comprise water present in an amount of less than about 1:1 by weight relative to the weight of the chlorhexidine gluconate, octenidine hydrochloride, or combinations thereof. In some embodiments, the composition may further comprise water present in an amount of less than about 1:1 (by weight relative to the weight of the chlorhexidine gluconate, octenidine hydrochloride, or combinations thereof), less than about 0.9:1, less than about 0.8:1, less than about 0.7:1, less than about 0.6:1, less than about 0.5:1, less than about 0.4:1, less than about 0.3:1, less than about 0.2:1, less than about 0.1:1, less than about 0.05:1, less than about 0.1:1, 0:1, or a value between any of the foregoing values, such as from about 0.5:1 to about 0.2:1, from about 0.9:1 to about 0.7:1, etc.

[0048] In some embodiments, the composition may further comprise a hydrophilic vehicle characterized by an HLB of greater than 10 in an amount of less than about 0.1:1 relative to the weight of chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof. In some embodiments, the composition may comprise a hydrophilic vehicle at less than about 0.1:1, less than about 0.05:1, less than about 0.01:1, less than about 0.005:1, less than about 0.001:1, or a value between any of the aforementioned values. In some embodiments, the composition does not contain a hydrophilic vehicle (0:1 w / w).

[0049] In some embodiments, the composition comprises C2 to C 22 Alkyl 1,2-diols and C3-C 22 It may not contain alkyl 1,3-diol.

[0050] In some embodiments, the composition comprises C 8~12 Alkyl 1,2-diols and C 8~12 It may not contain alkyl 1,3-diol.

[0051] In some embodiments, the composition has the formula: [ka] [In the formula, Each R a are independently -H or C 1~18 is alkyl, R b is C 4~22 is alkyl] The compound may not be contained.

[0052] In some embodiments, the composition has the formula: [ka] [In the formula, Each R c are independently -H or C 1~18 is alkyl, Each R d is independent, C 4~22is alkyl] The compound may not be contained.

[0053] In some embodiments, the composition does not contain monoacylglycerides.

[0054] In some embodiments, the composition does not contain one or more of glycerol, 1,2-propanediol, 1,2-pentanediol, 1,2-hexanediol, 1,2-octanediol, 1,2,6-trihydroxyhexane, 1,3-propanediol, 1,4-butanediol, 2-butene-1,4-diol, 1,3-butanediol, 3-methyl-1,3-butanediol, 1,3-cyclohexanediol, and 2,3-butanediol.

[0055] In some embodiments, the composition does not contain one or more of glyceryl monostearate, glyceryl monocaprate, glyceryl monolaurate, glyceryl monoisostearate, diethyl D-tartrate, diethyl L-tartrate, dibutyl L-tartrate, decaglyceryl tristearate, and glyceryl monooleate.

[0056] In some embodiments, the composition does not contain one or more of triethylene glycol, tetraethylene glycol, triethylene glycol monomethyl ether, diethylene glycol monomethyl ether, dipropylene glycol, sorbeth-6,1,3-dihydroxyacetone dimer, and ethylhexylglycerin.

[0057] In some embodiments, the composition does not contain a hydrophobic vehicle as described herein.

[0058] Hydrophobic Plasticizer In some embodiments, the hydrophobic plasticizer may be characterized by an HLB of about 10 or less. For example, the hydrophobic plasticizer may be characterized by an HLB of 10 or less, 9 or less, 8 or less, 7 or less, 6 or less, 5 or less, 4 or less, 3 or less, 2 or less, 1 or less, or a value between any of the foregoing values, such as about 6 to about 8, about 3 to about 7, etc. In some embodiments, the hydrophobic plasticizer may be characterized by an HLB of less than 5. In some embodiments, the hydrophobic plasticizer may be characterized by an HLB of less than 2.

[0059] In some embodiments, the hydrophobic plasticizer may include hydrogen-bonding groups separated by more than three consecutive atoms. For example, the hydrogen-bonding atoms may be separated by 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 consecutive atoms, or values ​​within a range between any of the aforementioned values, such as about 16 to about 18, about 4 to about 8 consecutive atoms. Without being bound by theory, the hydrogen-bonding atoms are separated by a flexible chain of consecutive atoms that adopts a chair-like or pseudo-chair-like stable configuration. In other words, the hydrogen-bonding atoms are separated in such a manner as to allow chelation of antiseptic compounds, such as chlorhexidine gluconate and octenidine hydrochloride. For example, hydrogen-bonding groups separated by four consecutive atoms can adopt a seven-membered ring conformation, while hydrogen-bonding groups separated by seven consecutive atoms can adopt a decalin-like chair arrangement.

[0060] In some embodiments, the hydrophobic plasticizer may be characterized by a hydroxyl number of at least about 20. In some embodiments, the hydrophobic plasticizer may be characterized by a hydroxyl number of about 20 to about 70. In some embodiments, the hydrophobic plasticizer may be characterized by a hydroxyl number of about 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, or a value within a range between any of the foregoing values, such as, for example, about 30 to about 70, about 40 to about 50, etc.

[0061] In some embodiments, the hydrophobic plasticizer may be characterized by an average molecular weight of about 0.5 kg / mol to about 6 kg / mol. In some embodiments, the hydrophobic plasticizer may have an average molecular weight of about 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, or 6 kg / mol, or a value between any of the foregoing values, such as about 1 kg / mol to 5 kg / mol, about 2 kg / mol to 4 kg / mol, etc.

[0062] In some embodiments, the hydrophobic plasticizer may solubilize chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof in an amount greater than about 1% by weight relative to the weight of the hydrophobic plasticizer at a temperature of about 20° C. to about 23° C. For example, the hydrophobic plasticizer may solubilize chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof in an amount greater than 1, 2, 3, 4, or 5% by weight (relative to the weight of the hydrophobic plasticizer), or a value within any of the aforementioned values, such as about 2% to about 3% by weight, about 3% to about 5% by weight, etc., at a temperature of about 20° C. to about 23° C. In some embodiments, the hydrophobic plasticizer may solubilize chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof in an amount up to about 5% by weight, up to about 6% by weight, up to about 7% by weight, up to about 8% by weight, up to about 9% by weight, or up to about 10% by weight.

[0063] In some embodiments, the hydrophobic plasticizer may include a polymer having at least two hydrogen bonding groups. For example, the hydrophobic plasticizer may be a polymer having 2, 3, 4, 5, 6, 7, 8, 9, or 10 hydrogen bonding groups.

[0064] In some embodiments, the hydrophobic plasticizer may include a polymer having at least one hydrogen bond donor.

[0065] In some embodiments, the hydrophobic plasticizer may include a polymer having at least two hydrogen bond donors.

[0066] In some embodiments, the hydrophobic plasticizer is selected from the group consisting of -OR, -O-, -C(O)-, -C(O)-O-, -SR, -N(R)(R), -C(O)-N(R)-, -OC(O)-N(R)-, and -N(R)-C(O)-N(R)-, where each R is independently selected from -H and -C 1~6 The polymer may include a polymer having hydrogen bond donors selected from the group consisting of alkyl, aryl, aryl, aryl and aryl groups.

[0067] In some embodiments, the hydrophobic plasticizer is selected from the group consisting of -OH and -NH(R), where R is -H and C 1~6 The hydrogen bond donor may be selected from the group consisting of alkyl, aryl, arylsulfates, and alkyls.

[0068] In some embodiments, the hydrophobic plasticizer may include two --OH groups.

[0069] In some embodiments, the hydrophobic plasticizer may be selected from polyester polyols, polyalkadiene polyols, and silicone polyols, or combinations thereof. The polyester polyols, polyalkadiene polyols, and silicone polyols of the present disclosure are described in more detail below.

[0070] Polyester polyol In some embodiments, the hydrophobic plasticizer may include a polyester polyol. a OH) under well-known conditions to form the acid HOC(O)R b or anhydride RC(O)OC(O)R 2 and react with it to obtain an ester (R a O.C.(O)R b It will be readily understood that one may produce a polyol having two or more ester moieties. Polyester refers to a molecule having two or more alcohol moieties. Thus, polyester polyol refers to a molecule having two or more esters and two or more alcohols.

[0071] In some embodiments, the hydrophobic plasticizer may include a polyester polyol having, on average, at least two hydroxyl (i.e., -OH) groups. In some embodiments, the polyester polyol may have a hydroxyl number of about 20 to about 70. In some embodiments, the polyester polyol may have a hydroxyl number of about 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, or 70, or a value within a range between any of the foregoing values, such as, for example, about 25 to about 50, about 20 to about 30, etc.

[0072] In some embodiments, the hydrophobic plasticizer may include a polyester polyol having a molecular weight of about 1500 to about 4000 kg / mol. In some embodiments, the polyester polyol may have a molecular weight of about 1500, 1600, 1700, 1800, 1900, 2000, 2200, 2400, 2600, 2800, 3000, 3200, 3400, 3600, 3800, or 4000 kg / mol, or a value between any of the foregoing values, such as about 2000 kg / mol to 3000 kg / mol, about 1800 kg / mol to 3600 kg / mol, etc.

[0073] In some embodiments, the hydrophobic plasticizer has formula (I): [ka] [In the formula, Each A is independently C2~C 22 Alkylene, C2-C 22 alkenylene, -A'-(cyclohexylenyl)-A'-, -A'-(cyclohexenyl)-A'-, and phenylene; These C2~C 22 Alkylene, C2-C 22 Alkenylene, cyclohexylenyl or cyclohexenyl is C1-C 20 Alkyl and C2-C 20 alkenyl, Each A' is independently C2 to C 16 Alkylene and C2-C 16alkenylene, each B is independently selected from: -OC(O)- and -C(O)O-; n is an integer from 4 to 10; At least one A is one or more C1~C 20 Alkyl and C2-C 16 C optionally substituted with alkenylene 14 ~C 22 Alkylene, one or more C1-C 20 Alkyl and C2-C 16 C optionally substituted with alkenylene 14 ~C 22 alkenylene, -A'-(cyclohexylenyl)-A'-, and -A'-(cyclohexenyl)-A'-. The polyester polyol may include a polyester polyol represented by:

[0074] In some embodiments, the polyester polyol is 16 ~C 44 Alkyl acids, C 16 ~C 44 Alkyl diacids, C2-C 12 Alkyl acids, C2-C 12 Alkenyl Acids, C2-C 12 Alkyl diacids, C2-C 12 Alkenyl diacids, C3-C 12 Alkyl triacid, C6-C 10 Aryl Acids, C6-C 10 Aryl diacids, C6-C 10 Aryl triacid, C 16 ~C 44 Alkanol, C 16 ~C 44 Alkyldiol, C2-C 10 Alkanols, C2-C 10 Alkyldiol, C3-C 10 It may be derived from an alkyl triol, a polyalkylene glycol, or a combination thereof.

[0075] In some embodiments, the polyester polyol may be derived from an acid such as oxalic acid, maleic acid, fumaric acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, undecanedioic acid, dodecanedioic acid, methanetricarboxylic acid, citric acid, aconitic acid, isocitric acid, tricarballylic acid, 1,3,5-trimethylcyclohexane-1,3,5-tricarboxylic acid, terephthalic acid, phthalic acid, isophthalic acid, ethylene glycol, polyethylene glycol, propylene glycol, polypropylene glycol, 1,4-butanediol, 1,5-pentanediol, 1,6-hexanediol, glycerol, or a combination thereof.

[0076] In some embodiments, the polyester is 16 ~C 44 Alkyl acids, C 16 ~C 44 Alkyl diacids, C2-C 12 Alkyl acids, C2-C 12 Alkyl diacids, C3-C 12 Alkyl triacid, C6-C 10 Aryl Acids, C6-C 10 Aryl diacids, C6-C 10 Aryl triacid, C 16 ~C 44 Alkanol, C 16 ~C 44 Alkyldiol, C2-C 10 Alkanols, C2-C 10 Alkyldiol, C3-C 10The alkyl triols may be derived from alkyl triols, oxalic acid, malonic acid, maleic acid, fumaric acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, undecanedioic acid, dodecanedioic acid, methanetricarboxylic acid, citric acid, aconitic acid, isocitric acid, tricarballylic acid, 1,3,5-trimethylcyclohexane-1,3,5-tricarboxylic acid, terephthalic acid, phthalic acid, isophthalic acid, ethylene glycol, polyethylene glycol, propylene glycol, polypropylene glycol, 1,4-butanediol, 1,5-pentanediol, 1,6-hexanediol, glycerol, or combinations thereof.

[0077] In some embodiments, the hydrophobic plasticizer is 16 ~C 44 Alkyl acids and C 16 ~C 44 In some embodiments, the hydrophobic plasticizer may comprise a polyester polyol derived from one or more of the alkyl diacids. 36 Alkyl diacid and C 36 It may also include polyester polyols derived from alkyl diols.

[0078] In some embodiments, the hydrophobic plasticizer is C2-C 12 Alkyl acids, C2-C 12 Alkyl diacids and C3-C 12 The hydrophobic plasticizer may include a polyester polyol derived from one or more of alkyl triacids. In some embodiments, the hydrophobic plasticizer may include a polyester polyol derived from oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, undecanedioic acid, dodecanedioic acid, methanetricarboxylic acid, citric acid, aconitic acid, isocitric acid, tricarballylic acid, 1,3,5-trimethylcyclohexane-1,3,5-tricarboxylic acid, or combinations thereof.

[0079] In some embodiments, the hydrophobic plasticizer is a C 10 Aryl Acids, C6-C10 Aryl diacids and C6-C 10 The hydrophobic plasticizer may include a polyester polyol derived from one or more of aryl triacids. In some embodiments, the hydrophobic plasticizer may include a polyester polyol derived from terephthalic acid, phthalic acid, isophthalic acid, or a combination thereof.

[0080] In some embodiments, the hydrophobic plasticizer is 16 ~C 44 Alkanols and C 16 ~C 44 In some embodiments, the hydrophobic plasticizer may include a polyester polyol derived from one or more of the alkyl diols, or a combination thereof.

[0081] In some embodiments, the hydrophobic plasticizer is C2-C 10 Alkanols, C2-C 10 Alkyl diols and C3-C 10 In some embodiments, the hydrophobic plasticizer may include a polyester polyol derived from one or more of an alkyl triol. In some embodiments, the hydrophobic plasticizer may include a polyester polyol derived from ethylene glycol, polyethylene glycol, propylene glycol, polypropylene glycol, 1,4-butanediol, 1,5-pentanediol, 1,6-hexanediol, glycerol, or a combination thereof.

[0082] In some embodiments, the hydrophobic plasticizer may include a polyester polyol derived from one or more of dimer acid, adipic acid, and 1,6-hexanediol.

[0083] In some embodiments, the hydrophobic plasticizer may include a polyester polyol derived from one or more of dimer acid and ethylene glycol.

[0084] In some embodiments, the hydrophobic plasticizer may include a polyester polyol derived from one or more of dimer acid, adipic acid, and ethylene glycol.

[0085] In some embodiments, the hydrophobic plasticizer may include a polyester polyol derived from one or more of a dimer acid and a dimer diol.

[0086] In some embodiments, the hydrophobic plasticizer may include a polyester polyol derived from one or more of dimer diol and isophthalic acid.

[0087] In some embodiments, the hydrophobic plasticizer may include a polyester polyol derived from one or more of dimer diol and terephthalic acid.

[0088] In some embodiments, the hydrophobic plasticizer may include one or more polyester polyol formulations sold under the trade name PRIPLAST™ (e.g., Priplast 3186, Priplast 3190, Priplast 3192, Priplast 3196, Priplast 3197, and Priplast 3238).

[0089] Polyalkadiene polyol In some embodiments, the hydrophobic plasticizer may include a polyalkadiene polyol. Polyalkadiene polyols are polymers derived from one or more conjugated diene monomers (i.e., homopolymers and copolymers) having an average of about 1.6 to 2 hydroxyl groups (-OH) per molecule. Conjugated diene refers to a moiety in which two olefins (i.e., -CR=CR-) are separated by a single carbon-carbon bond.

[0090] In some embodiments, the conjugated dienes used to prepare the polyalkadiene polyols of the present disclosure include 2-substituted or 2,3-disubstituted 1,3-dienes having from 4 to 12 carbon atoms. Examples of conjugated dienes include butadiene, isoprene, chloroprene, 2-cyano-1,3-butadiene, 2,3-dimethyl-1,2-butadiene, and the like.

[0091] In some embodiments, the polyalkadiene polyol is hydroxy-terminated. Hydroxy-terminated polyalkadiene polyols may be prepared according to U.S. Patent No. 5,416,168 (hereby incorporated by reference in its entirety), in which a lithiated silyl-protected alkanol is used as an initiator (and subsequently deprotected) and the polymer chain is terminated with ethylene oxide.

[0092] In some embodiments, the polyalkadiene polyol may have about 30-70% 1,4-addition (e.g., I+T+CH2=CH-CH=CH2→R-CH2-CH=CH-CH2-T). The preference for 1,4-addition (as opposed to 1,2-addition) may be provided by selecting conditions known in the art. For example, polybutadienes with 30-70% 1,4-addition minimize viscosity.

[0093] In some embodiments, the polyalkadiene polyol may have 80% or more of 1,4-addition. For example, polyisoprene having 80% or more of 1,4-addition may be used as a suitable T g and viscosity.

[0094] In some embodiments, the polyalkadiene polyol is not hydrogenated.

[0095] In some embodiments, the polyalkadiene polyol may be further hydrogenated, i.e., at least a portion of the olefins are reduced with hydrogen and a suitable catalyst. In some embodiments, the polyalkadiene polyol is hydrogenated such that 50-95% of the olefins are reduced. For example, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% of the olefins in the polyalkadiene polyol, or a value within a range between any of the aforementioned values, such as about 90% to about 95%, about 65% to about 85%, etc., may be reduced by hydrogenation. In some embodiments, 100% of the olefins in the polyalkadiene may be reduced.

[0096] In some embodiments, the hydrogenated polyalkadiene polyol may have about 40-60% 1,2-addition (e.g., I+T+CH2=CH-CH=CH2→R-CH2-CH(CH=CH2)-T). →The preference for 1,2-addition (as opposed to 1,2-addition) may be provided by selecting conditions known in the art. Hydrogenated polyalkadiene polyols, such as hydrogenated polybutadiene with 40-60% 1,2-addition, may prevent waxiness of the polymer.

[0097] In some embodiments, the hydrophobic plasticizer has the following formula II: [ka] [In the formula, Each R 1 is independently selected from C1-C6 alkyl substituted with -OH; Each A is independently -C(R 2 )=C(R 2 )-, -CH(R 2 )CH(R 2 )-, -C(R 2 )(C(R 2 )=CH2)-, -C(R 2 )(CH(R 2 )CH3)-; Each R 2is independently selected from -H, halogen, -CN, phenyl, C1-C6 alkyl, C1-C6 alkyl substituted with -OH; n is an integer between 10 and 200. The polyalkadiene polyol may include one or more polyalkadiene polyols represented by:

[0098] In some embodiments, one R 1 is -(CH2)6OH, and one R 1 is -CH2CH2OH.

[0099] In some embodiments, each A is -C(R 2 )=C(R 2 )-, and each R 2 is -H.

[0100] In some embodiments, each A is -C(R 2 )=C(R 2 )-, whereas R 2 is -H, while R 2 is C1-C6 alkyl, for example, -CH3.

[0101] In some embodiments, the polyalkadiene polyols may be characterized by an average molecular weight of about 500 to about 20,000. For example, the polyalkadiene polyols may be characterized by an average molecular weight of about 500, 600, 700, 800, 900, 1000, 2000, 3000, 4000, 5000, 6000, 7000, 8000, 9000, 10000, 12000, 14000, 16000, 18000, or 20000, or a value within a range between any of the foregoing values, such as about 12000 to about 18000, about 1000 to about 10000, etc.

[0102] In some embodiments, the polyalkadiene polyols may be characterized by a hydroxyl value of about 250 to about 10,000. For example, the polyalkadiene polyols may be characterized by a hydroxyl value of about 250, 500, 750, 1000, 2000, 3000, 4000, 5000, 6000, 7000, 8000, 9000, or 10000, or a value within a range between any of the foregoing values, such as, for example, about 500 to about 5000, about 1000 to about 8000, etc.

[0103] In some embodiments, the hydrophobic plasticizer may include a polyalkadiene polyol selected from Poly-BD R-45HT (ARCO Chemicals; Newtown Square, Pennsylvania), Polyvest HT (Evonik Industries; Essen Germany), Krasol LBH 2000 or LBH 3000 (Cray Valley USA LLC; Exton, Pennsylvania).

[0104] Silicone Polyol In some embodiments, the hydrophobic plasticizer may include a silicone polyol.

[0105] In some embodiments, the hydrophobic plasticizer has the following formula (III): [ka] [In the formula, Each R 1 and R 2 is independently selected from -OH, C1-C6 alkyl, C1-C6 alkyl substituted with -OH; Each A is independently -O-, C2 to C 10 alkyl, and phenyl; n is an integer from 10 to 200. The silicone polyol may include one or more silicone polyols represented by:

[0106] In some embodiments, each R 1is -OH.

[0107] In some embodiments, each R 1 is independently selected from C1-C6 alkyl substituted with -OH. For example, each R 1 may be -CH2CH2OH.

[0108] In some embodiments, each R 2 is selected from C1 to C6 alkyl. For example, each R 2 may be -CH3.

[0109] In some embodiments, n is 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 140, 160, 180, or 200, or a value between any of the foregoing values, such as, for example, from about 100 to about 160, from about 50 to about 90, etc.

[0110] In some embodiments, the hydrophobic plasticizer may comprise a silicone polyol characterized by a hydroxyl number of about 10 to about 200. For example, the silicone polyol may be characterized by a hydroxyl number of about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, or 200, or a range of values ​​between any of the foregoing values, such as, for example, about 50 to about 130, about 20 to about 70, etc.

[0111] In some embodiments, the hydrophobic plasticizer may include a silicone polyol selected from, such as, KF-6000, KF-6001, KF-6002, KF-6003, X-21-5841, KF-9701 (all available from Shin-Etsu Chemical Company), and combinations thereof.

[0112] Antibacterial adhesive In many embodiments, an antimicrobial adhesive is described. The antimicrobial adhesive may include any of the compositions and pressure sensitive adhesives described herein.

[0113] In some embodiments, the antimicrobial adhesive may consist essentially of the composition and a pressure sensitive adhesive.

[0114] In some embodiments, the antimicrobial adhesive has a glass transition temperature (T g In some embodiments, the antimicrobial adhesive may be characterized by a glass transition temperature (°C) of about -90°C, -80°C, -70°C, -60°C, -50°C, -40°C, -30°C, -20°C, -10°C, -5°C, 0°C, 5°C, or 10°C, or a value within a range between any of the aforementioned values, such as about -30°C to about -5°C, about -70°C to about 0°C, etc. The T of the antimicrobial adhesive may be characterized by a glass transition temperature (°C) of about -90°C, -80°C, -70°C, -60°C, -50°C, -40°C, -30°C, -20°C, -10°C, -5°C, 0°C, 5°C, or 10°C, or a value within a range between any of the aforementioned values, such as about -30°C to about -5°C, about -70°C to about 0°C, etc. g can be imparted by the action of a hydrophobic plasticizer on the pressure sensitive adhesive (i.e., the plasticizer lowers the glass transition temperature of the pressure sensitive adhesive).

[0115] In some embodiments, the antimicrobial adhesive may further comprise one or more tackifiers, antioxidants, pigments, reinforcing fillers, crosslinkers, and electrolytes.

[0116] Pressure Sensitive Adhesives In some embodiments, the pressure sensitive adhesive has a glass transition temperature (T g In some embodiments, the pressure sensitive adhesive may be characterized by a T of about -70°C, -60°C, -50°C, -40°C, -30°C, -20°C, -10°C, -5°C, 0°C, 5°C, 10°C, or 20°C, or a value within a range between any of the foregoing values, such as from about -20°C to about 5°C, from about -50°C to about -30°C, etc. g It can be characterized by:

[0117] In some embodiments, the pressure sensitive adhesive is selected from an acrylic polymer or copolymer. In some embodiments, the acrylic polymer or copolymer may be the reaction product of one of the monomers selected from alkyl (meth)acrylate, N-vinylpyrrolidone, N-vinylcaprolactam, (alkyl-substituted) acrylamide, (alkyl-substituted) methacrylamide, 2-hydroxyethyl (meth)acrylate or and combinations thereof.

[0118] Medical Supplies In various embodiments, a medical article is described. The medical article may include a substrate having a first surface and a second surface opposite the first surface, and an antimicrobial adhesive as described herein disposed on the first surface.

[0119] In some embodiments, the substrate may be a polymeric film. The polymeric film may be a woven or nonwoven fabric.

[0120] In some embodiments, the medical article may further comprise a release liner in contact with the antimicrobial adhesive. The release liner may protect the antimicrobial adhesive from contact with foreign matter prior to use. The release liner may further facilitate application of the medical article to a surface.

[0121] In some embodiments, the medical article can further include a delivery system in contact with the second surface. The delivery system can be, for example, a paper releasably secured to the second surface with an adhesive. The delivery system can provide structural integrity to the medical article to facilitate application to the surface of the medical article.

[0122] In some embodiments, the medical article may be configured in a variety of shapes, including custom shapes to fit over a contoured surface.

[0123] In some embodiments, the medical article may be in the form of a sheet or roll.

[0124] In some embodiments, the antimicrobial article is a tape or wrap.

[0125] In some embodiments, the medical article is a wound dressing. The medical article may be in the form of any wound dressing known in the art.

[0126] In some embodiments, the medical article is an intravenous dressing.

[0127] In some embodiments, the medical article is a surgical drape.

[0128] Methods for preparing compositions In various embodiments, methods are described for preparing the compositions described herein, which may include providing chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof and a hydrophobic plasticizer, and contacting the chlorhexidine gluconate with the hydrophobic plasticizer to form the composition.

[0129] In some embodiments, the chlorhexidine gluconate, octenidine hydrochloride, or combinations thereof are provided as solids, hi other embodiments, the chlorhexidine gluconate, octenidine hydrochloride, or combinations thereof are provided as aqueous solutions.

[0130] In some embodiments, the hydrophobic plasticizer is provided as a solution in a volatile non-polar organic solvent (eg, pentane, hexane, heptane, etc.).

[0131] In some embodiments, the method further comprises heating the mixture formed by contacting chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof with a hydrophobic plasticizer to a temperature (°C) of about 30°C, 40°C, 50°C, 60°C, 70°C, or 80°C, or a value within any of the aforementioned values, such as about 40°C to about 60°C, about 50°C to about 70°C, etc. In some embodiments, the heating may be performed under vacuum. Heating or heating under vacuum can remove the solvent and water. In some embodiments, the water may be removed by decantation, for example, using a separatory funnel.

[0132] In some embodiments, the method may further include removal of solvent and / or water by one or more of heating, vacuum (including rotary evaporation or freeze-pump-thaw techniques), distillation or azeotropic distillation, molecular sieves, and the like.

[0133] Method for preparing antibacterial adhesives In various embodiments, methods are described for preparing the antimicrobial adhesives described herein. The methods may include providing a composition and a pressure sensitive adhesive described herein, and contacting the composition with the pressure sensitive adhesive to form the antimicrobial adhesive.

[0134] In some embodiments, the composition may include water (w / w) in an amount less than about 1:1 relative to chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof. In some embodiments, water may be present in the composition in an amount (w / w) less than about 1:1, 0.9:1, 0.8:1, 0.7:1, 0.6:1, 0.5:1, 0.4:1, 0.3:1, 0.2:1, 0.1:1, 0.05, 0.01:1, 0.005:1, or 0.001:1 relative to chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof, or a range of values ​​between any of the aforementioned values, such as about 0.4:1 to about 0.05:1, about 0.1:1 to about 0.01:1, etc. In some embodiments, the composition may include only residual water, i.e., water present in an amount less than about 0.01% by weight, relative to the weight of the composition.

[0135] In some embodiments, the pressure sensitive adhesive may be prepared as a solvent-based solution. The solvent may be any organic solvent that is miscible with the pressure sensitive adhesive. For example, the solvent may include ethyl acetate, heptane, toluene, and methyl ethyl ketone, combinations thereof, and the like.

[0136] Method for preparing a medical article In various embodiments, methods are described for preparing the medical articles described herein. The methods may include providing an antimicrobial adhesive and a substrate described herein, and coating the antimicrobial adhesive onto the substrate.

[0137] In some embodiments, the substrate may be a polymeric backing material such as a thermoplastic polyurethane (e.g., as sold by ESTANE®) In other embodiments, the substrate may be a release liner, which can be made from a variety of materials such as paper, polycoated paper, polyester film, high density polyethylene film, silicone, etc.

[0138] In some embodiments, the antimicrobial adhesive may be coated with a thickness of about 50 to about 525 microns. For example, the thickness may be about 50, 75, 100, 125, 150, 175, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, or 525 microns, or any value between any of the foregoing values, such as about 100 microns to about 200 microns, about 75 microns to about 350 microns, etc.

[0139] In some embodiments, coating the antimicrobial adhesive onto a substrate may include manually spreading a uniform layer of the antimicrobial adhesive onto the substrate. Manual spreading can be accomplished using a knife edge coater.

[0140] In some embodiments, the method may further include drying the antimicrobial adhesive at an elevated temperature for a period of time to form a dried antimicrobial adhesive. For example, the antimicrobial adhesive may be dried at a temperature of about 65° C. to about 93° C. for about 1 minute to about 10 minutes.

[0141] In embodiments where the substrate may be a polymeric backing material, the method may further include contacting the dried antimicrobial adhesive with a release liner.

[0142] In embodiments where the substrate may be a release liner, the method may further include laminating the dried antimicrobial adhesive to a polymeric backing material. Lamination may be performed at room temperature using nip rollers.

[0143] Methods for disinfecting surfaces In various embodiments, a method for disinfecting a surface is described. The method may include providing a medical article as described herein and contacting the medical article with the surface for a period of time.

[0144] In some embodiments, the surface may be skin or tissue. In some embodiments, the skin or tissue is mammalian skin or tissue. In some embodiments, the tissue may be selected from mucosal tissue, chronic wounds, acute wounds, burns, and the like.

[0145] In some embodiments, the skin or tissue may be intact, i.e., undamaged.

[0146] In some embodiments, the skin or tissue may have a wound or other injury.

[0147] In some embodiments, the skin or tissue may be intact upon contact or may remain in contact when the skin is subjected to injury, e.g., cutting, puncturing, etc.

[0148] In other embodiments, the surface may be a medical surface, such as a surgical device (e.g., scalpel, scissors, blade, forceps, drape, etc.), a medical device (e.g., catheter, stent, artificial joint, dental implant, etc.), floor tile, countertop, pail, dish, glove, swab, cloth, sponge, foam, nonwoven fabric, and paper product.

[0149] In some embodiments, the medical articles may be effective against a variety of microbial types, such as gram positive bacteria, gram negative bacteria, fungi, protozoa, mycoplasma, yeast viruses, lipid enveloped viruses, and the like. For example, the antimicrobial adhesives and medical articles made therefrom may be effective against, for example, Staphylococcus, Streptococcus, Pseudomonas, Enterococcus, Escherichia, Aspergillus, Fusarium, Candida, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, Streptococcus pneumoniae, Enterococcus faecalis, vancomycin-resistant Enterococcus (VRE), Pseudomonas aeruginosa, Escherichia coli, Aspergillus niger, In one embodiment, the composition may be effective in reducing the number of and / or preventing the growth of microorganisms present on a surface, such as Aspergillus niger, Aspergillus fumigatus, Aspergillus clavatus, Fusarium solani, Fusarium oxysporum, Fusarium chlamydosporum, Candida albicans, Candida glabrata, and Candida krusei.

[0150] In some embodiments, the medical article may be in contact with the surface for a period of about 30, 60, 90, 120, 150, 180, or 210 minutes, or a value within a range between any of the foregoing values, such as, for example, about 30 minutes to about 120 minutes, about 90 minutes to about 180 minutes, etc.

[0151] In other embodiments, the antimicrobial article may contact the surface for a period of more than about 1, 2, 3, 4, 5, 12, or 24 hours, or a value within a range between any of the aforementioned values, e.g., about 2 to about 5 hours, about 12 to about 24 hours, etc. In some embodiments, the antimicrobial article may contact the surface for a period of about 1, 2, 3, 4, 5, 6, or 7 days, or a value within a range between any of the aforementioned values, e.g., about 1 to about 2 days, about 2 to about 5 days, etc.

[0152] In some embodiments, the method may further include applying water to the surface prior to contacting the medical article with the surface. Wetting the surface with water may facilitate migration of CHG or octenidine to the surface of the antimicrobial adhesive.

[0153] In some embodiments, the method may be effective to deliver chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof to a surface at an average rate of greater than 15 mcg / sq per hour. For example, the method may be effective to deliver chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof to a surface at an average rate (mcg / sq. per hour) of about 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, or 100, or a value between any of the foregoing values, such as about 30 to about 50, about 20 to about 60, etc. The amount of chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof delivered to a surface may be determined using the surface availability analysis described herein.

[0154] In some embodiments, the method may be a method for preparing a surface for incision, eg, surgery.

[0155] In some embodiments, the method may be a method for preparing a surface for needle penetration, for example, to administer intravenous medications or fluids, to withdraw fluids, or the like.

[0156] kit In various embodiments, kits are described. The kits may include a medical article as described herein and a set of instructions instructing a user to disinfect a surface according to the methods described herein.

[0157] In various embodiments, kits are described. The kits may include a medical article as described herein and a set of instructions instructing a user to prepare a surface for surgery according to the methods described herein. EXAMPLES

[0158] The objects and advantages of the present disclosure are further illustrated by the following examples, but the particular materials and amounts thereof recited in these examples, as well as other conditions and details, should not be construed to unduly limit the disclosure. These examples are merely for illustrative purposes and are not intended to limit the scope of the appended claims.

[0159] All parts, percentages, ratios, etc. in the examples and elsewhere herein are by weight unless otherwise indicated. Materials used in the examples and their suppliers are listed in Table 1. Solvents and other reagents used were obtained from Sigma-Aldrich Chemical Company (St. Louis, MO) unless otherwise noted. All water is distilled water and all molecular weights are weight average molecular weight unless otherwise noted.

[0160] The materials used in preparing the examples are summarized in Table 1. [Table 1]

[0161] Example 1: Solubility Screening A screening test was performed to determine the solubility of chlorhexidine gluconate (CHG) in hydrophobic vehicles. Screening was performed by diluting the hydrophobic vehicle in n-heptane and then suspending it in an appropriate amount of 20% w / v CHG aqueous solution. The vial containing the resulting suspension was placed on a hot plate equipped with a magnetic stirrer. It was heated at 65°C with constant stirring to flash off the heptane and water. After removing the heptane and water, the non-volatile residue containing the hydrophobic vehicle and chlorhexidine gluconate was applied to a glass microscope slide, cooled to room temperature, and observed in thin sections for transparency and clarity. Solubility was determined by visual observation, and a transparent translucent appearance indicated solubility of CHG in the hydrophobic vehicle. HLB values ​​were estimated from the molecular weight and structure, when available. If the structure was not available, the molecule was assumed to have a maximum of four ester groups and two hydroxyl groups. [Table 2]

[0162] Adhesive preparation procedure The adhesive composition was prepared by blending together a solvent-based pressure-sensitive adhesive (poly(isooctyl acrylate / N-vinylpyrrolidone) in an ethyl acetate / heptane / methanol blend obtained from 3M Company, St. Paul, MN), an aqueous solution of CHG, and a hydrophobic diol by simple hand stirring.

[0163] Adhesive Coating Procedure The adhesive composition was coated as a hand spread by applying a uniform layer of the prepared adhesive composition onto the release surface of a suitable release liner using a knife edge coater. The wet adhesive thickness ranged from 50 to 510 microns (2 to 20 mils). The coated adhesive composition was dried in a solvent oven at temperatures of 65°C to 93°C (150°F to 200°F) for 1 to 10 minutes.

[0164] Adhesive Lamination Procedure Adhesive articles were prepared with the dried adhesive by laminating it to a 0.8 mil thick Estane 58309 film using nip rollers at room temperature.

[0165] Surface availability analysis In some embodiments, a discrete amount of CHG should be available on the adhesive surface. Surface availability was determined by exposing the surface of the dried adhesive to water under static conditions according to the following method: A sample of the adhesive article sufficient to cover a circular area of ​​5.07 square centimeters was cut from a larger piece of the adhesive article prepared as described above. The release liner was removed to expose the surface of the dried adhesive, and water (50 mcL) was pipetted onto the adhesive surface and spread evenly to cover an area of ​​2.54 square centimeters. The sample was then incubated at 35°C in a humidified incubator at a relative humidity of about 70% for 90 minutes. After the desired test time had elapsed, the water was transferred to a liquid chromatography vial for analysis. The samples were analyzed by reversed-phase HPLC using absorbance detection on an Agilent 1200 HPLC system consisting of a quaternary gradient pump, an autosampler, a heated column compartment, and a variable wavelength detector. A 5.0 mcL portion of the sample solution was injected onto a MACMOD Analytical Inc. 150 x 3 mm ACE 3 micrometer C18 column. The column was equilibrated at 0.50 mL / min and 40°C with 80 / 20 (v / v) water / methanol containing 40 mM pH 3.7 ammonium formate buffer. After injection, the sample was eluted with a 30 minute linear gradient to 20 / 80 (v / v) water / methanol containing 40 mM pH 3.7 ammonium formate buffer. This eluent composition was held at constant composition for 5 minutes before re-equilibrating in the starting eluent. Absorbance detection of the 254 ± 2 nm signal was used to quantify the sample concentration of chlorhexidine gluconate relative to a standard solution containing chlorhexidine acetate ("CHA"). A mole fraction of 1.435 was applied for quantification to account for the molar ratio of CHG / CHA (898 / 626).

[0166] Example 2 The following examples demonstrate the release of CHG from drape samples made with adhesive formulations containing different α,ω-diols (A1-A5) and the effect of diol concentration on the release (A5, A6). The compositions of the adhesives used in samples A1-A6, their estimated HLB values, and CHG release results are shown in Table 3. [Table 3]

[0167] Direct Time Death Analysis Several samples of the coated adhesives were subjected to antimicrobial performance testing according to the following 90 minute time kill test: A suspension of MSSA, E. coli, or C. albicans was diluted to 1 x 10 in phosphate buffered water (pbw) using a McFarland Equivalence Turbidity Standard of 0.5. 8 The suspension was prepared at a concentration of colony forming units (CFU) / milliliter (mL). Using an Eppendorf pipette, 50 microliters (μL) of this suspension was transferred as 15-16 separate droplets onto the adhesive surface of a 2.5 cm diameter section of adhesive film. These inoculated samples were then incubated at room temperature (23 + / - 2 °C) for 5-30 minutes. After incubation, the samples were placed in 20 mL of neutralization buffer and sonicated for 1 minute, followed by vortexing for 2 minutes. Portions of the resulting solution were serially diluted in phosphate-buffered water. The stock solution and dilutions were each plated onto 3M PETRIFILM aerobic counting plates (3M Company, St. Paul, MN) and incubated for at least 24 hours. The 3M PETRIFILM plates were then counted using a 3M PETRIFILM plate reader (Model 6499, 3M Company).

[0168] Example 3 In Example 3, the antimicrobial activity of drape samples made with adhesive A5 was evaluated after aging at room temperature for different times. For the placebo, CHG was omitted from composition A5 and replaced with additional base PSA. The results are shown in Table 4. Antimicrobial activity of greater than 4 log was demonstrated in all cases against representative Gram-positive (MSSA), Gram-negative (E. coli) and yeast (C. albicans) organisms. [Table 4]

[0169] Knee flexion model study A knee flexion model was used to evaluate the drape adhesion to skin and drape removal performance of chlorhexidine gluconate (CHG) antimicrobial incise drapes. The knee flexion model was used to simulate surgical conditions.

[0170] For testing, subjects sat or lay on a padded examination table. If an excessive amount of hair was present at the test site, the area was trimmed before testing began to ensure good contact of the sample with the skin. Both legs were prepped with the desired surgical preparation, CHLORAPREP HI-LITE ORANGE (Becton-Dickinson, Franklin Lakes, NJ). The skin preparation was allowed to air dry for at least 3 minutes, after which the legs were draped. For each subject, two 3 inch by 10 inch drape samples were applied to each leg longitudinally above the knee on the left and right sides of the midline. A gap of approximately ¼ inch to ½ inch was left between the two drapes, approximately 3 inches above the patella to 3 inches below the knee.

[0171] Drape samples were worn for approximately 30 minutes. Drape lift was assessed after a dry flex challenge (flexing and straightening the knee 10 times until comfortable), a wet flex challenge (applying saline-soaked gauze to cover the midline for 5 minutes followed by flexing the knee 10 times), and a pulsed lavage challenge (applying 200-300 cc of saline along the midline between the two drapes using a low-setting pulsed lavage). The area of ​​drape lift was marked and photographed after each challenge. At the end of the pulsed lavage lift assessment, the drape sample and excess skin preparation were removed. Evaluations of skin condition (irritation and peeling), adhesive residue, ease of removal, and subject pain level were performed after drape removal. Geometric means of lift area (mm2) and lift frequency (%) were reported for all subjects in each clinical study.

[0172] Example 4 Adhesive A5 was used to make a representative CHG drape using the procedure described above. A comparative adhesive (C1) was also used to make a comparative drape. Both adhesive formulations are provided in Table 5. Results of the knee flexion model study of the representative CHG drape, the comparative drape, and a commercially available Ioban drape (3M Company) are provided in Table 6. The lift area (geometric mean of non-zero values) and drape lift frequency (percentage of drape samples exhibiting any amount of lift) after washing were observed to be statistically not different for the A5 and 3M Ioban incise drapes. The C1 drape was statistically inferior to both of these drapes in lift area and lift frequency, highlighting the advantage of using a diol plasticizer in which the hydrogen bonding groups are separated by more than three carbon atoms on the molecule. [Table 5] [Table 6]

[0173] Equivalent Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments specifically described herein which equivalents are intended to be encompassed by the following claims.

Claims

1. chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof; a hydrophobic plasticizer having at least two hydrogen bonding groups separated by more than three consecutive atoms; the hydrophobic plasticizer is characterized by a hydrophilic-lipophilic balance of 10 or less as determined using the HLB method; The composition, wherein the hydrophobic plasticizer is capable of solubilizing chlorhexidine gluconate in an amount of at least 2 g per 100 g at a temperature of 20-23°C.

2. 10. The composition of claim 1, wherein the chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof is present in an amount of about 0.2% to about 5% by weight based on the weight of the composition.

3. 10. The composition of claim 1, wherein the chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof is present in an amount of about 0.1% to about 20% by weight based on the weight of the hydrophobic plasticizer.

4. The composition of claim 1, wherein the hydrophobic plasticizer is present in an amount of about 10% to about 50% by weight based on the weight of the composition.

5. 10. The composition of claim 1, wherein the hydrophobic plasticizer is characterized by an average molecular weight of from about 0.5 kg / mol to about 6 kg / mol and a hydroxyl number of at least about 20.

6. The hydrophobic plasticizer has the formula (I): 【Chemical 1】 [In the formula, Each A is independently C ２ ~C ２２ Alkylene, C ２ ~C ２２ selected from alkenylene, -A'-(cyclohexylenyl)-A'-, -A'-(cyclohexenyl)-A'-, and phenylene; Said C ２ ~C ２２ alkylene, ２ ~C ２２ The alkenylene, the cyclohexylenyl, or the cyclohexenyl is C １ ~C ２０ Alkyl, and C ２ ~C ２０ alkenyl, Each A' is independently C ２ ~C １６ Alkylene and C ２ ~C １６ alkenylene; each B is independently selected from —C(O)O— and —OC(O)—; n is an integer from 4 to 10, At least one A is C １ ~C ２０ Alkyl and C ２ ~C １６ C optionally substituted with one or more of alkenylene １４ ~C ２２ Alkylene, C １ ~C ２０ Alkyl and C ２ ~C １６ C optionally substituted with one or more of alkenylene １４ ~C ２２ alkenylene, -A'-(cyclohexylenyl)-A'-, and -A'-(cyclohexenyl)-A'-; Formula (II): 【Chemistry 2】 [In the formula, each R 1 is independently selected from C 1 -C 6 alkyl substituted with —OH; each A is independently selected from -C(R 2 )=C(R 2 )-, -CH(R 2 )CH(R 2 )-, -C(R 2 )(C(R 2 )=CH 2 )-, -C(R 2 )(CH(R 2 )CH 3 )-; each R 2 is independently selected from —H, halogen, —CN, phenyl, C 1 -C 6 alkyl, C 1 -C 6 alkyl substituted with —OH; n is an integer from 10 to 200; or Formula (III): 【Chemistry 3】 [In the formula, each R 1 and R 2 is independently selected from —OH, C 1 -C 6 alkyl, C 1 -C 6 alkyl substituted with —OH; each A is independently selected from —O—, C 2 -C 10 alkyl, and phenyl; n is an integer from 10 to 200. The composition of claim 1, comprising a compound represented by any one of the following:

7. 10. The composition of claim 1, wherein the hydrophobic plasticizer is derived from oxalic acid, maleic acid, fumaric acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, undecanedioic acid, dodecanedioic acid, methanetricarboxylic acid, citric acid, aconitic acid, isocitric acid, tricarballylic acid, 1,3,5-trimethylcyclohexane-1,3,5-tricarboxylic acid, terephthalic acid, phthalic acid, isophthalic acid, ethylene glycol, polyethylene glycol, propylene glycol, polypropylene glycol, 1,4-butanediol, 1,5-pentanediol, 1,6-hexanediol, glycerol, or a combination thereof.

8. The hydrophobic plasticizer is C １６ ~C ４４ Alkyl acids, C １６ ~C ４４ Alkyl diacid, C ２ ~C １２ Alkyl acids, C ２ ~C １２ Alkenyl Acids, C ２ ~C １２ Alkyl diacid, C ２ ~C １２ Alkenyl diacids, C ３ ~C １２ Alkyl triacid, C ６ ~C １０ Aryl acids, C ６ ~C １０ Aryl diacids, C ６ ~C １０ Aryl triacid, C １６ ~C ４４ Alkanol, C １６ ~C ４４ Alkyl diol, C ２ ~C １０ Alkanol, C ２ ~C １０ Alkyl diol, C ３ ~C １０ alkyltriol, polyalkylene glycol, or a combination thereof; one or more of a C 6 -C 10 aryl acid, a C 6 -C 10 aryl diacid, and a C 6 -C 10 aryl triacid; terephthalic acid, phthalic acid, isophthalic acid, or combinations thereof; one or more of C 16 -C 44 alkanols and C 16 -C 44 alkyldiols; one or more of a C 2 -C 10 alkanol, a C 2 -C 10 alkyl diol, and a C 3 -C 10 alkyl triol; or Ethylene glycol, polyethylene glycol, propylene glycol, polypropylene glycol, 1,4-butanediol, 1,5-pentanediol, 1,6-hexanediol, glycerol, or a combination thereof The composition of claim 1 derived from

9. The hydrophobic plasticizer is a polyester polyol comprising one or more of dimer acid, adipic acid, and 1,6-hexanediol; a polyester polyol comprising one or more of a dimer acid and ethylene glycol; a polyester polyol comprising one or more of dimer acid, adipic acid, and ethylene glycol; a polyester polyol comprising one or more of a dimer acid and a dimer diol; a polyester polyol comprising one or more of dimer diol and isophthalic acid; and Polyester polyol containing one or more of dimer diol and terephthalic acid The composition of claim 1 selected from:

10. The composition of claim 1 , wherein the hydrophobic plasticizer is characterized by an HLB of less than 5.

11. further comprising water present in an amount less than about 1% by weight based on the weight of the composition; or 10. The composition of claim 1, further comprising water present in an amount of less than 1:1 by weight to the weight of chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof.

12. 10. The composition of claim 1, further comprising a hydrophilic vehicle in an amount less than 0.1:1 by weight relative to chlorhexidine gluconate, octenidine hydrochloride, or a combination thereof, wherein the hydrophilic vehicle is characterized by a hydrophilic-lipophilic balance of greater than 10.

13. does not contain a hydrophilic vehicle, said hydrophilic vehicle being characterized by a hydrophilic-lipophilic balance of greater than 10; does not contain C8-12 alkyl 1,2-diol and C8-12 alkyl 1,3-diol; formula: 【Chemistry 4】 [In the formula, each R a is independently —H or C 1-18 alkyl; R b is C 4-22 alkyl. or formula: 【Chemistry 5】 [In the formula, each R c is independently —H or C 1-18 alkyl; Each R d is independently C 4-22 alkyl. does not contain the compound The composition of claim 1 characterized by one or more of:

14. A composition according to any one of claims 1 to 13; and a pressure sensitive adhesive.

15. A medical article, a substrate having a first surface and a second surface opposite the first surface; and the antimicrobial adhesive of claim 14 disposed on said first surface.

16. 1. A method of disinfecting a surface, said method comprising: contacting the surface with the medical article of claim 15; and contacting the medical article with the surface for a period of time.

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