POLOXAMER COMPOSITIONS WITH REDUCED COLLOIDAL-GEL (SOL-GEL) TRANSITION TEMPERATURES AND METHODS FOR REDUCING THE COLLOIDAL-GEL (SOL-GEL) TRANSITION TEMPERATURE.

Abstract

The reduction in the colloidal-gel temperature of aqueous poloxamer surfactant compositions is achieved through the addition of hydrophobic vicinal diols. The lowering of the colloidal-gel temperature and the gel-forming efficiency of water-soluble poloxamer block copolymers of polyethylene oxide-β-polypropylene oxide-β-polyethylene oxide have been significantly improved by the addition of small amounts of at least one hydrophobic vicinal diol, such as monoalkyl glycols, monoalkyl glycerols, or monoacyl glycerols. The lowering of the colloidal-gel temperature facilitates gel formation, and these gels exhibit longer residence times on a surface, particularly those with biological properties.

Description

[001] This description generally refers to the reduction in the colloidal-gel solution temperature of aqueous poloxamer surfactant compositions by the addition of hydrophobic vicinal diols. The hydrophobic vicinal diols comprise monoalkyl glycols, monoalkyl glycerols, and monoacyl glycerols. The decrease in the colloidal-gel solution temperature facilitates a higher viscosity of the composition, where the higher viscosities allow for a longer residence time on a surface, particularly those of biological origin. Background of the Invention

[002] Poloxamers are triblock copolymers of poly(ethylene oxide) and poly(propylene oxide) that have thermoreversible properties, transforming from a liquid-like to a gel-like behavior above a certain temperature and composition percentage in aqueous systems. This phenomenon is called the colloidal-to-gel (sol-gel) transition, most often represented by the colloidal-to-gel transition temperature, Tsol-gel. The colloidal-to-gel transition can also be influenced by certain excipients. By varying the concentration of poloxamer and other excipients, hydrogels with a colloidal-to-gel transition point close to body temperature can be achieved. This transition is reversible by decreasing the temperature, the poloxamer concentration, or changing the excipients.

[003] The structure of poloxamers is usually arranged as poly(ethylene oxide-co-propylene oxide-co-ethylene oxide) or, conversely, poly(propylene oxide-co-ethylene oxide-co-propylene oxide). Poloxamers generally appear as white, waxy, fluid surfactants. For water-soluble poloxamers, monomolecular micelles form at low concentrations (10⁻⁴–10⁻⁵ wt%). However, higher concentrations result in multimolecular aggregates consisting of a hydrophobic core with their hydrophilic poly(ethylene oxide) chains oriented outward. At a given temperature, micellization occurs in dilute compositions in selected solvents above the critical micelle concentration. At higher concentrations, above a critical gel concentration, the micelles can arrange themselves into a network.

[004] Commonly used poloxamer types include Poloxamer 188, (also called Pluronic>;F-68), Poloxamer 237 (also called Pluronic' F-87), Poloxamer 338 (also called Pluronic F-108), and Poloxamer 407 (also called Pluronic' F-127), which are freely soluble in water. The F designation refers to the flake form of the product. Poloxamer 407 (Pluronic' F-127) has good solubility, low toxicity, and has been used for biomedical applications.

[005] Poloxamer 407 has an HLB (hydrophobic-lipophilic equilibrium) value of 22. In general, HLB values ​​>10 indicate an affinity for water (hydrophilic), and values ​​<10 indicate an affinity for oil (lipophilic). Aqueous compositions of Poloxamer 407 exhibit thermoversible properties, transitioning from liquid-like to gel-like behavior above the colloidal-gel transition temperature. Above the colloidal-gel transition temperature, the compositions behave more solidly, while below the colloidal-gel transition temperature, they behave more liquidly (fluid). The rheological flow behavior of poloxamer compositions can be Newtonian (liquid-like) or non-Newtonian (gel-like) depending on the temperature and polymer concentration.Below the colloidal solution-gel transition temperature, poloxamer compositions exhibit Newtonian properties, while above the colloidal solution-gel transition point they exhibit non-Newtonian properties.

[006] In addition to temperature, gel formation also depends on the poloxamer concentration in the composition. Gel formation occurs when the poloxamer concentration is above the critical micelle concentration. Poloxamer compositions with concentrations of 20–30% by weight form clear liquids at cool temperatures of 4–5 °C, but form a gel at room temperature (–22–25 °C). The gel can revert to a liquid upon cooling.

[007] The colloidal solution-gel transition temperature decreases with increasing poloxamer concentration.

[008] Excipients can also influence the colloidal-to-gel transition temperature of poloxamers. For example, hydrochloric acid, propylene glycol, and ethanol increase the colloidal-to-gel transition temperature, while sodium chloride, NacHPCU, and sodium alginate, as well as an increase in pH and ionic resistance, decrease the gel-to-sol transition temperature. Gel systems have been used primarily in topical biomaterials for the sustained release of active pharmaceutical agents. The sustained release of these drugs helps maintain therapeutic drug concentrations over a longer period and helps decrease dosing intervals, thereby increasing patient compliance.

[009] There has been extensive research on poloxamers, which has resulted in several patent filings including, but not limited to, U.S. Patent 7,879,320, U.S. Patent No. 4,188,373, U.S. Patent No. 6,482,435, EP Publication No. 1982696, U.S. Patent Application Publication No. 2016 / 0144038, U.S. Patent Application Publication No. 2009 / 0017120, U.S. Patent Application Publication No. 2012 / 0277199, U.S. Patent Application Publication No. 2015 / 0071864, PCT Publication No. WO2014 / 027006, U.S. Patent No. 8,829,053 and EP Patent Publication No. 2490722. Brief Description of the Invention

[0010] In various embodiments, a method is provided for lowering the colloidal-gel solution temperature of an aqueous poloxamer gel composition by up to 12 °C. The method includes adding 0.1 to 1.8 wt% of hydrophobic vicinal diols to the aqueous poloxamer gel composition, wherein the hydrophobic vicinal diols are monoalkyl glycols, monoalkyl glycerols, monoacyl glycerols, monoalkyl glycols of 6 to 16 carbons in length, or a combination thereof.

[0011] Additional features and advantages will be set forth in the detailed description that follows, and will in part be readily apparent to those skilled in the art from that description or will be recognized by the practice of the modalities as described herein, including the detailed description that follows, the claims, as well as the accompanying drawings.

[0012] Both the preceding general description and the following detailed description are understood to be illustrative and intended to provide a general overview or framework for understanding the nature and character of the claims. The accompanying drawings are included to provide further understanding and are incorporated into and form a part of this specification. The drawings illustrate one or more embodiments and, together with the description, serve to explain the principles and operation of the various embodiments. Brief Description of the Figures

[0013] Figure 1 is a graph showing the average colloidal-gel solution temperatures of poloxamer 407 after the addition of six-carbon chain monoalkyl glycols (06) and monoalkyl glycerols at 0-1.8% by weight.

[0014] Figure 2 is a graph showing the average colloidal-gel temperatures of Poloxamer 407 after the addition of monoalkyl glycerols, monoacyl glycerols, and monoalkyl glycols from C1 to C12 at 0-1.8 wt%.

[0015] Figure 3 is a graph showing the average colloidal-gel temperatures of Poloxamer 407 after the addition of monoalkyl glycerols, monoacyl glycerols, and monoalkyl glycols from C12 at 0-1.8 wt%.

[0016] Figure 4 is a graph showing the formalized data of the colloidal-gel temperature changes for vicinal diols (Cg to C1e), using the colloidal-gel temperatures of Co.

[0017] Figure 5 is a graph showing the flow measured in centimeters of 17 wt% poloxamer 407 compared to poloxamer 407 after the addition of linear and nonlinear Cg monoalkyl glycerols at 0.9 wt%. Detailed Description of the Invention

[0018] The following will refer in detail to the present preferred modalities, examples of which are illustrated in the attached figures.

[0019] This description generally refers to the reduction in the colloidal solution-gel temperature of aqueous poloxamer surfactant compositions (which may be poloxamer gel solutions, poloxamer gel suspensions, poloxamer gel mixtures, etc.) by the addition of hydrophobic vicinal diols. It has been surprisingly found that the lowering of the colloidal solution-gel temperature and the gel-forming efficiency of water-soluble poloxamer block copolymers of polyethylene oxide-β-polypropylene oxide-β-polyethylene oxide are markedly improved by the addition of small amounts of at least one hydrophobic vicinal diol. Examples of hydrophobic vicinal diols useful for use in poloxamer gel compositions include monoalkyl glycols, monoalkyl glycerols, monoacyl glycerols, and combinations thereof.The decrease in temperature of the colloidal gel solution facilitates gel formation (for example, on a biological surface), where these gels allow for a longer residence time on a surface in the applied environment, particularly those with biological properties. If an active ingredient, such as a cosmetic agent, a biological agent, a pharmaceutical agent, a wound-healing agent, an enzymatic agent, or an antimicrobial agent, is added to this system, the active agent will therefore remain in close contact with the biological surface for an extended period.

[0020] One of the problems associated with topically applied formulations is their short duration of action, often caused by their limited residence time at the target site. A major challenge in delivering active agents (e.g., drugs and wound-healing agents) to body cavities and surfaces is, therefore, maintaining the active agent at the desired site of action for a sufficient period to achieve targeted delivery and, consequently, highly effective treatment of the medical or cosmetic condition.

[0021] In some embodiments, a poloxamer gel composition is described comprising 0.05 to 5 wt% of a hydrophobic vicinal diol component, and 10 to 65 wt% of a poloxamer component. The hydrophobic vicinal diol component is monoalkyl glycerols, monoacyl glycerols, monoalkyl glycols of 6 to 16 carbons in length, or a combination thereof, and wherein the hydrophobic vicinal diol component reduces a colloidal-gel solution temperature of the aqueous poloxamer equivalent by at least 1.0°C.

[0022] In some embodiments, the hydrophobic vicinal diol component comprises at least 0.075 wt%, or at least 0.1 wt%, or at least 0.15 wt%, or at least 2.0 wt% of the poloxamer gel composition. In some embodiments, the hydrophobic vicinal diol component is less than 5 wt%, or less than 4 wt%, or less than 3.5 wt%, or less than 3.0 wt%, or less than 2.5 wt%, or less than 2.0 wt%, or less than 1.8 wt% of the poloxamer gel composition.

[0023] In some embodiments, the hydrophobic vicinal diol component is completely solubilized in the poloxamer gel composition. In some embodiments, the hydrophobic vicinal diol component is completely solubilized in the poloxamer gel composition without any non-poloxamer surfactant.

[0024] In some forms, the poloxamer component is selected from the group consisting of Poloxamer 108, Poloxamer 124, Poloxamer 188, Poloxamer 127, Poloxamer 237, Poloxamer 238, Poloxamer 288, Poloxamer 335, Poloxamer 338, Poloxamer 407 and combinations thereof.

[0025] In some forms, the composition is aqueous.

[0026] In some embodiments, the hydrophobic vicinal diol component reduces the colloidal-gel solution temperature of the aqueous poloxamer equivalent by at least 1.0°C. In some embodiments, the hydrophobic vicinal diol component depresses the colloidal-gel solution temperature of the aqueous poloxamer equivalent by at least 1.5°C, at least 2.0°C, at least 2.5°C, at least 3.0°C, at least 3.5°C, or at least 4.0°C, or at least 4.5°C, or at least 5.0°C. As used herein, the aqueous poloxamer equivalent refers to an aqueous composition consisting solely of water and the specified percentage of poloxamer component with no additional components or ingredients.

[0027] In some embodiments, the colloidal-gel solution temperature of the aqueous poloxamer equivalent is at least 26.5°C. In some embodiments, the colloidal-gel solution temperature of the aqueous poloxamer equivalent is at least 27.0°C, or at least 27.5°C, or at least 28.0°C, or at least 28.5°C, or at least 29°C.

[0028] The proximal diols useful in the poloxamer gel compositions described herein include hydrophobic monoalkyl glycols, monoalkyl glycerols, and monoacyl glycerols. Monoalkyl glycerols are also referred to as glycerol alkyl ethers, while monoacyl glycerols are also referred to as glycerol alkyl esters. The substituents on the monoalkyl glycol, monoalkyl glycerol, and monoacyl glycerol are preferably aliphatic and may be linear or branched, and saturated or unsaturated, with the two hydroxyl groups close to each other.

[0029] The monoalkyl glycols useful in the poloxamer gel compositions described herein may have a structure represented by formula 1, as follows: Formula 1

[0030] where R = branched or unbranched C6-C16 alkyl group or alkyl group. In some embodiments, R = branched or unbranched C6-C14 alkyl group or alkyl group, or R = branched or unbranched C8-C12 alkyl group or alkyl group.

[0031] Monoalkyl glycerols (alternatively called glycerol alkyl ether) useful in the poloxamer gel compositions described herein may have a structure represented by formula 2, as follows: OH HO / L ΟχR formula 2 where R = branched or unbranched C6-C16 alkyl group. In some embodiments, R = branched or unbranched C6-C14 alkyl group, or R = branched or unbranched C8-C12 alkyl group.

[0032] The monoacyl glycerols useful in the poloxamer gel compositions described herein may have a structure represented by formula 3 as follows: OH R formula 3 where R = branched or unbranched C6-C16 alkyl group. In some embodiments, R = branched or unbranched C6-C14 alkyl group, or R = branched or unbranched C8-C12 alkyl group.

[0033] For each of the vicinal diols, when R branches, the respective compound can exist as a racemic mixture of R,S components, as a pure enantiomer of R or S configuration, or as a mixture enriched with R,S enantiomer.

[0034] Examples of specific monoalkyl glycols include, but are not limited to, 1,2-hexanediol, 1,2-heptanediol, 1,2-octanediol (caprylyl glycol), 1,2-nonanediol, 1,2-decanediol, 1,2-undecanediol, 1,2-dodecanediol, 1,2-tridecanediol, 1,2-tetradecanediol, 1,2-pentadecanediol, and 1,2-hexadecanediol.

[0035] Examples of specific monoalkyl glycerols include, but are not limited to, glycerol-l-hexyl ether, glycerol-l-heptyl ether, glycerol-l-octyl ether, glycerol-1-(2-ethylhexyl) ether (also known as octoxyglycerin, 2-ethylhexylglycerin, 3-(2-ethylhexyloxy)propane-1,2-diol, and Sensiva® SC 50), glycerol-l-nonyl ether, glycerol-l-decyl ether, glycerol-1-1-undecyl ether, glycerol-l-dodecyl ether, glycerol-1-tridecyl ether, glycerol-1-tetradecyl ether, glycerol-1-pentadecyl ether, and glycerol-hexadecyl ether.

[0036] Examples of specific monoacyl glycerols include, but are not limited to, glyceryl monohexanoate (2,3-dihydroxypropyl hexanoate), glyceryl monoheptanoate (2,3-dihydroxypropyl hexanoate), glyceryl monoctanoate (2,3-dihydroxypropyl octanoate, monocapri 1in), glyceryl monononanoate, glyceryl monodecanoate (glyceryl 1-decanoate), glyceryl monoundecanoate (2,3-dihydroxypropyl undecanoate), glyceryl monododecanoate (monolaurin, also called glyceryl monolaurate and Lauricidin®), glyceryl monotridecanoate, glyceryl monotetradecanoate (monomyristin), glyceryl monopentadecanoate, glyceryl monohexadecanoate, glyceryl monoheptadecanoate, glycerol monopentadecanoate and glycerol monohexadecanoate.

[0037] In some embodiments, the vicinal diol is a combination of a monoalkyl glycol and a monoalkyl glycerol. In some embodiments, the vicinal diol is a combination of a monoalkyl glycol and a monoacyl glycerol. In some embodiments, the vicinal diol is a combination of a monoalkyl glycerol and a monoacyl glycerol. In some embodiments, the vicinal diol is a monoalkyl glycol, a monoalkyl glycerol, and a monoacyl glycerol.

[0038] While long-chain vicinal diols may have poor water solubility, poloxamers act as compatibilizers (e.g., surfactants), so the addition of high concentrations of poloxamer facilitates the overall solubility of vicinal diols in the compositions described herein.

[0039] As used herein, poloxamers refers to nontoxic, nonionic triblock copolymers composed of a central hydrophobic polyoxypropylene (polypropylene oxide) chain coupled by two hydrophilic polyoxyethylene (poly(ethylene oxide)) chains at the alpha, omega positions. Because the lengths of the polymer blocks can be customized, many different poloxamers exist, each with slightly different properties. For the generic term poloxamer, these copolymers are commonly designated by the letter P (for poloxamer) followed by three digits: the first two digits multiplied by 100 give the approximate molecular mass of the polyoxypropylene core, and the last digit multiplied by 10 gives the percentage of polyoxyethylene content (e.g., P407 = poloxamer with a polyoxypropylene molecular mass of 4000 g / mol and a polyoxyethylene content of 70.4%).For the trade names Pluronic and Synperonic, the coding for these copolymers begins with a letter to define their physical state at room temperature (L = liquid, P = paste, F = flake (solid)) followed by two or three digits. The first digit (two digits in a three-digit number) in the numerical designation, multiplied by 300, indicates the approximate molecular weight of the hydrophobic component; and the last digit multiplied by 10 gives the percentage content of polyoxyethylene (for example, F-108 indicates a molecular weight of polyoxypropylene of 3000 g / mol and a polyoxyethylene content of 80%).

[0040] In some forms, the poloxamer surfactant, or surfactant, may be Poloxamer 108, Poloxamer 127, Poloxamer 188, Poloxamer 237, Poloxamer 238, Poloxamer 288, Poloxamer 335, Poloxamer 338, Poloxamer 407, or combinations thereof. In certain embodiments, the surfactant may be Poloxamer 338. In certain other embodiments, the surfactant may be Poloxamer 407. In water at room temperature (-24°C), Poloxamer 338 (Pluronic© F-108) has been shown to gel at 30% by weight, while Poloxamer 407 (Pluronic© F127) gels at 20% by weight.

[0041] Any of the compositions described herein may be aqueous compositions. As used herein, aqueous compositions refer to a spectrum of water-based compositions including, but not limited to, homogeneous solutions in water with solubilized components, emulsified compositions in water stabilized by surfactants or hydrophilic polymers, and homogeneous or viscous emulsified or gelled compositions in water.

[0042] If maintenance of osmolarity is required, examples of suitable tonicity-adjusting agents that may be included in poloxamer gel compositions include, but are not limited to: sodium chloride and potassium chloride, glycerin, propylene glycol, mannitol, and sorbitol. These agents are commonly used individually in amounts ranging from approximately 0.01 to 2.5% (w / v) and preferably from approximately 0.05 to approximately 0.05%. Petrolatum, lanolin, mineral oil, dimethicone, and siloxy compounds are common emollients.Other emollients include isopropyl palmitate, isopropyl myristate, isopropyl isostearate, isostearyl isostearate, diisopropyl sebacate, propylene dipelargonate, 2-ethylhexyl isononoate, 2-ethylhexyl stearate, cetyl lactate, lauryl lactate, isopropyl lanolate, 2-ethylhexyl salicylate, cetyl myristate, oleyl myristate, oleyl stearate, oleyl oleate, hexyl laurate, isohexyl laurate, lanolin, olive oil, cocoa butter, shea butter, octyldodecanol, hexyldecanol dicapryl ether, and decyl oleate. Humectants include lecithin and polyethylene glycol. Moisturizers work by attracting water to the outer layer of the skin.

[0045] It is often desirable to include water-soluble viscosity enhancers in the poloxamer gel compositions described herein. Due to their demulcent effect and potential hydrophobic interactions with biological tissue, which aid in the retention of compositions on a surface, particularly one of biological origin, water-soluble polymers can improve the interaction of compositions with a surface. Because of this behavior, these water-soluble polymers can increase the residence time of the composition on a surface.

[0046] The water-soluble polymers useful herein include, but are not limited to, aloe vera, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, polyquaternium-1, polyquaternium-6, polyquaternium-10, guar, hydroxypropylguar, hydroxypropylmethylguar, cationic guar, carboxymethylguar, hydroxymethylchitosan, hydroxypropylchitosan, carboxymethylchitosan, N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan chloride, water-soluble chitosan, hyaluronic acid and its salts, chondroitin sulfate, heparin, dermatan sulfate, amylose, amylopectin, pectin, locust bean gum, alginate, dextran, carrageenan, xanthan gum, gellan gum, scleroglucan, schizophyllan, gum Arabic gum, ghatti gum, karaya gum, tragacanth gum, pechinas, starch and its modifications, tamarind gum, poly(vinyl alcohol), poly(ethylene oxide), poly(ethylene glycol), poly(methyl vinyl ether), polyacrylamide, poly(N,N-dimethylacrylamide), poly(N-vinylacetamide),poly(N-vinylformamide), poly(2-hydroxyethyl methacrylate), poly(glyceryl methacrylate), poly(N-vinylpyrrole done), poly(N,N-dimethylaminoethyl methacrylate), poly(N,N-dimethylaminopropylacrylamide), polyvinylamine, poly(N-isopropylacrylamide), and poly(N-vinylcaprolactam), the latter two hydrated below their lower critical solution temperatures, and similar polymers and combinations thereof. These water-soluble polymers can be used in quantities ranging from approximately 0.01 to approximately 10.0 percent by weight.

[0047] The most preferred hydrophilic polymers comprise hydroxyethylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, hydroxypropylguar, hydroxymethylchitosan, poly(ethylene oxide), N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan chloride, with hydroxyethylcellulose and hydroxymethylpropylcellulose being the most preferred.

[0048] If chelating agents are required to sequester metal ions, such as those found in matrix metalloproteinases (MMPs), enzymes that can impede tissue formation and healing by breaking down collagen, or in the removal of these metal ion deposits in structures, the chelating agent is selected from any compound that is capable of sequestering monovalent or polyvalent metal ions, such as preferably including calcium, magnesium, barium, cerium, cobalt, copper, iron, manganese, nickel, strontium, or zinc, and is pharmaceutically or veterinarily acceptable if used in biological tissue.

[0049] Suitable chelating agents include, but are not limited to, citric acid, citrate salts, aminocarboxylic acids, ethylenediaminetetraacetic acid (EDTA), nitrilotriacetic acid, nitrilotripropionic acid, diethylenetriaminepentaacetic acid, 2-hydroxyethylethylenediaminotriacetic acid, 1,6-diaminohexamethylenetetraacetic acid, 1,2-diaminocyclohexanetetraacetic acid, O,O'-bis(2-aminoethylene glycoltetraacetic acid, 1,3-diaminopropanetetraacetic acid, N,N'-bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid, ethylenediamine-N,N'-diacetic acid, ethylenediamine-N,N'-dipropionic acid, triethylentetraaminohexacetic acid, ethylenediamine-N,N'-bis(methylenephosphonic acid), iminodiacetic acid, N,N-bis(2-hydroxyethyl)glycine, 1,3diamino-2-hydroxypropanetetraacetic acid, 1,2diaminopropanetetraacetic acid, ethylenediaminetetrakis(methyl phonic acid), N-(2-hydroxyethyl 1)iminodiacetic acid and bisphosphonates such as etidronate, and salts thereof.Suitable chelating agents include, for example, but are not limited to, hydroxyalkylphosphonates as described in U.S. Patent No. 5,858,937, specifically the tetrasodium salt of 1-hydroxyethylidene-1,1-diphosphonic acid, also referred to as tetrasodium etidronate, commercially available from Monsanto Company as sodium salt or diphosphonic acid phosphonate DeQuest 2016.

[0050] The especially preferred chelating agents are mixed salts of EDTA such as disodium, trisodium, tetrasodium, dipotassium, tripotassium, tetrapotassium, lithium, dilithium, ammonium, diammonium, triammonium, tetraammonium, calcium and calcium-disodium, more preferably disodium, trisodium or tetrasodium salts of EDTA, and more preferably disodium EDTA and trisodium EDTA. The concentration of chelating agent can vary from 0.01% to 1.0% by weight, or from 0.025 to 0.5% by weight, or from 0.05 to 0.15% by weight.

[0051] In addition to a homogeneous solution, poloxamer gel compositions may also be an emulsion, a miniemulsion, a microemulsion, or an inverse emulsion that utilizes the surfactant poloxamer to solubilize an active agent that is normally insoluble in water or difficult to solubilize.The organic and inorganic active agents that can be solubilized include, but are not limited to, antibiotics, silver salts and silver nanoparticles, zinc salts and zinc, magnesium salts, phosphorus compounds, iodine compounds, antibacterial agents, antifungal agents, antiviral agents, antiprotozoal agents, antimicrobials, analgesics, protease inhibitors, antiallergics, anti-inflammatories, vasoconstrictors, vasodilators, coagulation agents, hormones, peptides, nucleic acids, saccharides, lipids, glycolipids, glycoproteins, endocrine hormones, growth hormones, growth factors, water-soluble low molecular weight collagen, collagen peptides, gelatin, heat shock proteins, immune response modifiers, anticancer agents, cytokines and mixtures thereof, as well as organic solvents that provide increased oxygen to ischemic wounds.Of importance are the addition of organic solvents, such as siloxanes and fluorocarbons, which increase oxygen solubility and transport. Particularly important is the use of a volatile, non-burning, non-stinging, non-sensitizing hexamethyldisiloxane (HMDS) siloxane solvent. The emulsion is prepared by slowly adding the HMDS to the composite composition until the concentration reaches the point where phase separation occurs between the organic solvent and the emulsified composition.

[0052] Essential oils may also be added to poloxamer gel compositions as fragrance or aromatherapy agents and / or as antimicrobial agents, including thymol, menthol, sandalwood, camphor, agatosma, cardamom, cinnamon, jasmine, lavender, frankincense, myrrh, geranium, juniper, menthol, pine, lemon, rose, eucalyptus, clove, orange, peppermint, linalool, spearmint, lemongrass, bergamot, citronella, cypress, nutmeg, fir, tea tree, winter green (methyl salicylate), vanilla, hemp essential oil, and the like.

[0053] In topical applications, poloxamer gel compositions can be supplied in various forms. Examples include, but are not limited to, liquids, creams, foams, lotions, gels, and sprays. These compositions can also be absorbed via swabs, cloth, sponges, foams, dressing materials, and non-medical products. 4. Tissues and paper products, such as paper towels and wipes.

[0054] As used herein, hydrophobic refers to repelling water, being insoluble or relatively insoluble in water, and lacking an affinity for water. When hydrophobic compounds are mixed with hydrophilic substituents, such as vicinal diols, which have amphiphilic character, the mixture may form emulsions in water, with or without added surfactant.

[0055] As used herein, HLB (hydrophobolipophilic equilibrium) is an empirical expression for the ratio of hydrophilic (water-attracting) and hydrophobic (water-repelling) surfactant properties, with HLB >10 having an affinity for water and numbers <10 having an affinity for oil (lipophilic).

[0056] As used herein, hydrogel refers to a three-dimensional polymer network swollen in water that is insoluble in aqueous media.

[0057] As used herein, a thermosensitive polymer refers to a polymer that responds to a change in temperature with a change in at least one of its physical, chemical, or mechanical properties. Hydrogels made of thermosensitive materials exhibit a temperature-mediated phase transition that causes changes in their volume and rheological properties, such as viscosity and viscoelasticity.

[0058] As used herein, the term ambient temperature may be an interval between 18 °C and 27 °C, and more particularly between 20 °C and 25 °C.

[0059] As used herein, the term body temperature is the average temperature of the human body which usually comprises a range between 36.0 °C and 37.5 °C.

[0060] As used herein, an antimicrobial agent kills or inhibits the growth of microorganisms. Antimicrobial agents can be grouped according to the microorganisms against which they primarily act. For example, antibacterial agents act against bacteria, antifungal agents act against fungi, antiviral agents act against viruses, and antiprotozoal agents act against protozoa.

[0061] As used herein, anti-inflammatory agents include, but are not limited to, water-soluble derivatives of aspirin, vitamin C, methylsulfonylmethane, tea tree oil, and non-steroidal anti-inflammatory drugs.

[0062] As used herein, an antiseptic agent inhibits the growth of externally applied microorganisms.

[0063] As used herein, antiviral agents treat infections caused by viruses. Antiviral agents do not destroy the target pathogen, but inhibit its growth.

[0064] As used herein, antifungal agents destroy or prevent the growth of fungi.

[0065] As used herein, active pharmaceutical ingredients (APIs) refers to chemical compounds that are therapeutically or prophylactically effective and induce a desired biological effect.

[0066] In some modalities, the gel-forming compositions described herein may provide sustained delivery and / or release of antimicrobial agents to a wound surface.

[0067] In some modalities, the gel-forming compositions described herein may provide a slightly acidic pH to enhance wound healing.

[0068] As used herein, water-soluble low molecular weight collagen is frequently referred to as collagen peptides, which are small bioactive peptides frequently from the enzymatic hydrolysis of collagen.

[0069] In some forms, the biologically active agent is biodegradable by human and animal cells.

[0070] In some forms, the biologically active agent is biodegradable and non-cytotoxic to human and animal cells.

[0071] In some embodiments, poloxamer gel compositions contain one or more biologically active agents. In some embodiments, any of the biologically active agents may be present independently in an amount ranging from 0.001 wt% to 25 wt%, or from 0.01 wt% to 20 wt%, or from 0.1 wt% to 10 wt%, or from 1 wt% to 5 wt%, or any combination of these starting and ending points.

[0072] A non-limiting list of examples of biologically active agents includes, but is not limited to, antibiotics, antimicrobial agents, antifungal agents, antiviral agents, antibacterial agents, antiprotozoal agents, antipruritic agents, antiacne agents, arthritis agents, rosacea agents, psoriasis agents, analgesics, anesthetics, astringents, anorectal agents, antihistamines, anti-inflammatory agents, nonsteroidal anti-inflammatory drugs (NSAIDs), moisturizers, antimitotics, anticancer agents, scabicides, pediculicides, antiperspirants, deodorants, eczema agents, antipsoriatic agents, antiseborrheic agents, biologically active proteins and peptides, water-soluble low molecular weight collagen, collagen peptides, gelatin, heat and radiation burn treatment agents, cancer treatment agents, wart removal agents, depigmenting agents,Agents for the treatment of diaper rash, keratolytic agents, enzymes, agents for joint pain, hair growth stimulants, vitamins, hemostatics, agents for the treatment of canker sores, agents for the treatment of cold sores, agents for dental and periodontal treatment, photosensitizing active substances, skin protective / barrier agents, agents for skin treatment, spheroids, including hormones and corticosteroids, agents for the treatment of sunburn, sunscreens, active transdermal nasal agents, active vaginal agents, agents for the treatment of warts, wound debridement agents, wound treatment agents, wound healing agents, antimicrobial wound agents, and retinoids (including retinol, retinoic acid, and retinoic acid derivatives).

[0073] In some embodiments, low molecular weight water-soluble collagen, also known as collagen peptides, is added as a biodegradable gel or powder to aid in wound healing. In some embodiments, the percentage of low molecular weight water-soluble collagen is less than 60% by weight of the poloxamer gel composition, or less than 50% by weight, or less than 40% by weight. In some embodiments, the percentage of low molecular weight water-soluble collagen is at least 2% by weight of the poloxamer gel composition, or at least 5% by weight, or at least 7% by weight.

[0074] In some forms, the topical antibiotic agents useful in the poloxamer gel compositions described herein include, but are not limited to, neomycin, quinamycin, streptomycin, erythromycin, clindamycin, rifampicin, rifamycin, penicillin G, penicillin V, ampicillin, amoxicillin, bacitracin, polymyxin, tetracycline, chlortetracycline, oxytetracycline, doxycycline, cephalexin, cephalothin, chloramphenicol, gentamicin, neomycin, kanamycin, streptomycin, erythromycin, clindamycin, rifamycin, bactracin, polymyxin, chlortetracycline, oxytetracycline, doxycycline; cephalexin and cephalothin.

[0075] In some embodiments, the topical antimicrobial agents for planktonic bacteria and biofilms useful in the poloxamer gel compositions described herein include, but are not limited to, bisbiguanides, such as alexidine and chlorhexidine and their respective salts, polymeric biguanides, such as poly(hexamethylene biguanide) and its salts, and other cationic polymers, such as polyquaternium-1, polyquaternium-6, polyquaternium-10, cationic guar, water-soluble chitosan derivatives, polydialdimethylammonium salts, poly(N,N-dimethylaminoethyl methacrylate), poly(N,N-dimethylaminopropyl acrylamide), polyvinylamine, and combinations thereof. Antimicrobial metals such as copper, zinc, tin, and silver, and salts thereof, may also be incorporated into the formulation as dispersed or micellarized components.

[0076] In some formulations, the topical antifungal agents useful in the poloxamer gel compositions described herein include, but are not limited to, clotrimazole, miconazole, ketoconazole, itraconazole, fluconazole, metronidazole, astemizole, omeprazole, econazole, oxiconazole, sulconazole, ketoconazole, terbinafine, tolnaftate, undecylenic acid, naftifine, butenafine, and mixtures thereof.

[0077] In some modalities, the topical antiviral agents useful in the poloxamer gel compositions described herein include, but are not limited to, acyclovir, foscarnet sodium, ribavirin, vidarabine, ganeiclovir sodium, zidovudine, phenol, amantadine hydrochloride, interferon alpha3, and podophyllotoxin.

[0078] In some modalities, the topical thermal burn treatment agents useful in the poloxamer gel compositions described herein include, but are not limited to, silver sulfadiazine, cerium nitrate-silver sulfadiazine, mafenide acetate, silver nitrate solution 0.5%, debriding agents, chlorhexidine, povidone-iodine, mupirocin, hydrocolloid dressings, hydrogel dressings, gentamicin, bacitracin, norfloxacin, and bismuth tribromophenate petroleum mixture.

[0079] Wounds are an ideal environment for the formation of biofilm communities due to their susceptibility to contamination and the availability of substrate and nutrients for biofilm attachment. Chronic wound infections share two important attributes with other biofilm diseases: persistent infection that is not cleared by the host's immune system and resistance to systemic and topical antimicrobial agents.

[0080] Common bacteria found in biofilms include Gram-positive Enterococcus faecalis, Staphylococcus aureus, Micrococcus spp. and beta-hemolytic Streptococcus (S. pyogenes, S. agalactiae), as well as Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia. Additionally, both facultative and strictly anaerobic bacterial genera have been detected in the wound biofilm, including Anaerococcus spp., Finegoldia spp., Parvimonas spp., Peptoniphilus spp., Peptostreptococcus spp., Staphylococcus spp., Bacteroides spp., Porphyromonas spp., and Fusobacterium spp. Prevotella spp. and Finegoldia spp.

[0081] Fungi are also found in wounds. These fungi include Candida spp. and Cladosporidium spp., as well as Aspergillus spp., Penicillium spp., Alternaria spp., Pleospora spp., Fusarium spp., Trichosporon asahii, Rhodotorula spp., and Trichtophyton spp., among others.

[0082] The wound environment can promote the formation of multispecific biofilms between bacteria and fungi in wounds.

[0083] The modalities of the description herein are also applicable to treating a microbial biofilm on a patient or inanimate surface by contacting the microbial biofilm with a composition comprising a poloxamer composition gelled in aqueous media containing antimicrobial agents and / or active pharmaceutical ingredients (APIs).

[0084] In some forms, the topical antiprolozoal drugs useful in the poloxamer gel compositions described herein include, but are not limited to, chloroquine, pyrimethamine, mefloquine, hydroxychloroquine; metronidazole, flornithine, furazolidone, melarsoprol, nifursemizone, nitazoxanide, ornidazole, paromomycin sulfate, pentamidine, quinapyramine, and tinidazole.

[0085] In some formulations, the topical anti-inflammatory agents useful in the poloxamer gel compositions described herein include, but are not limited to, water-soluble derivatives of aspirin, vitamin C, methylsulfonylmethane, acetylsalicylic acid, celecoxib, diclofenac, diflunisal, etodolac, ibuprofen, indomethacin, ketoprofen, ketorolac, nabumetone, naproxen, oxaprozin, piroxicam, salsalate, sulindac, tolmetin, indomethacin, meclofenamate sodium, fenoprobene calcium, mefenamic acid, nabumetone, ketorolac tromethamine, onaguase oil, jojoba oil, mesalamine, salicylic acid, choline magnesium tralisylate, flunisolide, triamolone, triamolone acetonide, dipropionate of beclomethasone, dipropionate, hydrotisorone, cortisone, dexamethasone, prednisone, methyl prednisolone, zinc and prednisolone.

[0086] In some modalities, the topical radiation burn treatment agents useful in the poloxamer gel compositions described herein include, but are not limited to, corticosteroids, topical antibiotics, aloe vera, and calendula ointment.

[0087] In some modalities, topical analgesics for pain relief useful in the poloxamer gel compositions described herein include, but are not limited to, acetaminophen, aspirin, ibuprofen, naproxen, diclofenac, opioids, COX-2 inhibitors, cannabidiol, and NSAIDs.

[0088] In some modalities, the topical arthritis and joint pain agents useful in the poloxamer gel compositions described herein include, but are not limited to, cannabidiol, nonsteroidal anti-inflammatory drugs, corticosteroids, TNF inhibitors, disease-modifying antirheumatic drugs, acetaminophen, codeine, capsaicin, methyl salicylate, methotrexate, sulfasalazine, and analgesic agents.

[0089] In some modalities, the joint pain agents useful in the poloxamer gel compositions described herein include, but are not limited to, acetaminophen, codeine, corticosteroids, capsaicin, methyl salicylate, NSAIDs, methotrexate, and sulfasalazine.

[0090] In some forms, topical treatments for cold sores, also called fever blisters, usually caused by herpes simplex virus 1 (HSV-1), useful in the poloxamer gel compositions described herein include, but are not limited to, acyclovir, valacyclovir, famciclovir, penciclovir, docosanol, aloe vera, aspirin, ibuprofen, acetaminophen, docosanol, benzocaine, dibucaine, menthol, camphor, benzyl alcohol, allantoin, petrolatum, cocoa butter, glycerin, zinc compositions, antimicrobial agents, tea tree oil, hydrocortisone, benzocaine, camphorated phenol, dimethicone, lidocaine, and allantoin.

[0091] In some formulations, topical oral ulcer treatments useful in the poloxamer gel compositions described herein include, but are not limited to, benzocaine, lidocaine, hydrogen peroxide, carbamide peroxide, fluocinonide, chlorhexidine, doxycycline, tetracycline, minocycline, hydrocortisone hemuccinate, eucalyptus, menthol, beclomethasone, dexamethasone, corticosteroids, benzydamine, diclofenac, and antifungal agents.

[0092] In some formulations, periodontal treatments useful in the poloxamer gel compositions described herein include, but are not limited to, chlorhexidine, doxycycline, minocycline, amoxicillin, metronidazole, tetracycline, and hydrogen peroxide.

[0093] In some modalities, topical eczema agents for treating skin inflammation characterized by itching, red skin, blisters and rash, useful in the poloxamer gel compositions described herein, include, but are not limited to, corticosteroid creams, tacrolimus, pimecrolimus, crisaborol and moisturizers.

[0094] In some forms, the topical scabicides for killing scabies mites useful in the poloxamer gel compositions described herein include, but are not limited to, permethrin, crotamiton, sulfur ointment, lindane, benzyl benzoate, and keratolytic cream.

[0095] In some forms, the topical pediculicides for the treatment of head lice useful in the poloxamer gel compositions described herein include, but are not limited to, lindane, malathion, carbaryl, pyrethrum, permethrin, phenothrin and allethrin, proteases and dimethicone.

[0096] In some formulations, topical antiseborrheic agents effective in seborrheic dermatitis (dandruff) and useful in the poloxamer gel compositions described herein include, but are not limited to, selenium sulfide, zinc pyrithione, corticosteroids, imidazole antifungals, salicylic acid, sodium sulfacetamide, tea tree oil, eucalyptus oil, ketoconazole, sulfur, and coal tar.

[0097] In some formulations, topical wart removal agents useful in the poloxamer gel compositions described herein include, but are not limited to, salicylic acid, cantharidin, tretinoin, and glycolic acid.

[0098] In some forms, topical depigmenting agents that inhibit melanogenesis (the pigmentation pathway by which cells produce melanin) useful in the poloxamer gel compositions described herein include, but are not limited to, hydroquinone, 4-hydroxyanisole, fluocinolone, tretinoin, adapalene, hydroquinone monobenzyl ether, azelaic acid, kojic acid, niacinamide, and serine protease inhibitors.

[0099] In some forms, the topical antipruritic agents useful in the poloxamer gel compositions described herein include, but are not limited to, antihistamines (diphenhydramine, hydroxyzine), enzymes, corticosteroids, doxepin, anesthetics such as lidocaine, prilocaine, pramoxine, capsaicin, polidocanol, menthol, N-palmitoylethanolamine, topical calcineurin inhibitors, and topical vitamin D modulators.

[00100] In some modalities, topical treatments for diaper dermatitis (or irritant diaper dermatitis) useful in the poloxamer gel compositions described herein include, but are not limited to, barrier creams, petrolatum, mild topical cortisones, zinc creams, topical antibiotics, calendula extract, and antifungal agents.

[00101] In some modalities, the enzymes in topical skin treatment useful in the poloxamer gel compositions described herein include, but are not limited to, bromelain, papain, ficin, amylase, actinidin, collagenase, phospholipase, and lipase.

[00102] In some forms, the topical rosacea agents useful in the poloxamer gel compositions described herein include, but are not limited to, brimonidine, azelaic acid, metronidazole, and sulfacetamide.

[00103] In some forms, topical psoriasis agents, particularly for plaque psoriasis, useful in the poloxamer gel compositions described herein include, but are not limited to, topical corticosteroids, topical retinoids, anthralin, vitamin D3, salicylic acid, and moisturizers.

[00104] In some formulations, the topical anorectal agents, particularly for hemorrhoids, useful in the poloxamer gel compositions described herein include, but are not limited to, hydrocortisone, witch hazel, aloe vera, and lidocaine.

[00105] In some formulations, the topical keratolytic agents for softening and facilitating the exfoliation of epidermal cells useful in the poloxamer gel compositions described herein include, but are not limited to, salicylic acid, urea, lactic acid, allantoin, glycolic acid, resorcinol, benzoyl peroxide, and trichloroacetic acid.

[00106] In some forms, the topical astringents that are drying agents that precipitate protein and shrink and tighten the skin useful in the poloxamer gel compositions described herein include, but are not limited to, aluminum triacetate, aluminum sulfate plus calcium acetate, alum, calamine, acacia, sage, yarrow, witch hazel, wax tree, distilled vinegar, very cold water, rubbing alcohol, glycerin, silver nitrate, potassium permanganate, zinc oxide, zinc sulfate, tincture of benzoin, and tannic and gallic acids.

[00107] In some forms, the topical moisturizers used to protect, hydrate, and lubricate the skin useful in the poloxamer gel compositions described herein include, but are not limited to: (i) emollients, including cholesterol, fatty acids, fatty alcohols, squalene, and pseudoceramides, (ii) humectants, including glycerol, propylene glycol, panthenol, sorbitol, urea, alpha hydroxy acids, and hyaluronic acid, (iii) occlusives, including petrolatum, beeswax, mineral oil, silicones, cyclomethicone, lanolin, and zinc oxide, and (iv) protein rejuvenators, including collagen, gelatin, elastin, and keratin.

[00108] In some forms, the topical corticosteroids, a class of spheroid hormones, useful in the poloxamer gel compositions described herein include, but are not limited to, cortisol, corticosterone, aldosterone, hydrocortisone, methylprednisolone, prednisolone, prednisone, triamcinolone, amcinonide, budesonide, desonide, fluocinolone, acetonide, fluocinonide, halcinonide, triamcinolone acetonide, beclomethasone, betamethasone, dexamethasone, fluocortolone, halomethasone, and mometasone, alclomethasone dipropionate, betamethasone dipropionate, betamethasone valerate, clobetasol propionate, clobetasone butyrate, fluprednidenum acetate, mometasone furoate, fluticasone, ciclesonide, cortisone acetate, hydrocortisone aceponate, hydrocortisone acetate, hydrocortisone buteprate, hydrocortisone butyrate, hydrocortisone valerate, prednicarbate and tixocortol pivalate.

[00109] In some forms, the topical anti-acne agents useful in the poloxamer gel compositions described herein include, but are not limited to, benzoyl peroxide, glycolic acid, lactic acid, salicylic acid, sulfur, tea tree oil, tretinoin, erythromycin, clindamycin, tetracycline, doxycycline, minocycline, azelaic acid, isotretinoin, tretinoin, adapalene, tazarotene, and Manuka essential oil.

[00110] In some modalities, topical treatment chemotherapy drugs such as cancer drugs applied directly to the skin useful in the poloxamer gel compositions described herein include, but are not limited to, 5-fluorouracil, diclofenac, ingenol mebutate, and imiquimod.

[00111] In some forms, topical antiperspirants, which attempt to stop or significantly reduce perspiration, useful in the poloxamer gel compositions described herein include, but are not limited to, aluminum chlorohydrate, aluminum zirconium tetrachlorohydrex glycine, and aluminum zirconium trichlorohydrex glycine.

[00112] In some forms, topical deodorants, which are designed to eliminate odor, useful in the poloxamer gel compositions described herein include, but are not limited to, perfumes, essential oils, sodium stearate, stearyl alcohol, potassium alum, and ammonium alum.

[00113] In some forms, the hair growth stimulants useful in the poloxamer gel compositions described herein include, but are not limited to, minoxidil, finasteride, biotin, and dihydrotestosterone.

[00114] In some modalities, the skin treatment vitamins useful in the poloxamer gel compositions described herein include, but are not limited to, vitamin C, vitamin E, vitamin D, vitamin K, vitamin B1, vitamin B3, vitamin B5, vitamin B6, biotin, choline, folic acid and vitamin E analogues (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid).

[00115] In some forms, the topical antioxidants useful in the poloxamer gel compositions described herein include, but are not limited to, selenium, vitamin A, vitamin C, vitamin E, vitamin K, coenzyme Q10, curcumin, resveratrol, retinol, epigallocatechin-3 gallate, polyphenol, flavonoids, glutathione, beta-carotene, lutein, lycopene, zeaxanthin, resveratrol, zinc, manganese, cisterna, curcumin, astaxanthin, alpha-lipoic acid, carnosine, glutathione, polyphenols, quercetin, soy isoflavones, superoxide dismutase, Allium species, catalase, ellagic acid, and melatonin.

[00116] In some formulations, sunscreen agents may be either chemical or physical. Physical sunscreen agents useful in the poloxamer gel compositions described herein include, but are not limited to, zinc oxide and titanium dioxide, which provide broad-spectrum UVA (320–400 nanometers) and UVB (290–320 nanometers) protection and are gentle on the skin. Chemical sunscreen agents, however, may be solubilized or suspended and added to a sunscreen formulation to result in a transparent or translucent coating on the skin.In some embodiments, sunscreen chemicals include, but are not limited to, avobenzone (butiImethoxydibenzoylmethane; 4-tert-butyl-4'-methoxydibenzoylmethane), homosalate (homomentyl salicylate; 2-ethylhexyl; 2-ethylhexyl 2-hydroxybenzoate), octocrylene (2-ethylhexy12-cyano-3,3-diphenyl-2-acrylate; 2-ethylhexyl-2-cyano-3,3diphenyl-2-propenoate), oxybenzone (benzophenone-3; (2-hydroxy4-methoxyphenyl) phenylmethanone; 2-hydroxy-4-methoxybenzophenone), octinoxate (methoxylate Ethylhexyl; octyl methoxycinnamate) and combinations thereof. Avobenzone is absorbed in UVA, homosalate is absorbed in UVB, octisalate is absorbed in UVB, octocrylene is absorbed in UVB, oxybenzone is absorbed in UVA and UVB, and otinoxate is absorbed in UVB.In order to slow down the photodegradation of avobenzone and otinoxate, photostabilizers such as polysilicone-15 (polydimethylsiloxane-based oligomeric UV absorber), undecylcrylene dimethicone, diethylhexyl-2,6-naphthalate, ethylhexyl methoxycrylene, and the like can be added.

[00117] In some forms, the topical sunburn agents useful in the poloxamer gel compositions described herein include, but are not limited to, emollient creams, topical aloe vera, and over-the-counter pain relievers.

[00118] In some modalities, the topical wound-healing agents useful in the poloxamer gel compositions described herein include, but are not limited to, hyaluronic acid, antimicrobial dressings, growth factors, stem cells, collagen, oxygen, nutrients including proteins, carbohydrates, arginine, glutamine, polyunsaturated fatty acids, vitamin A, vitamin C, vitamin E, magnesium, copper, zinc and iron, biodegradable scaffolds, heparan sulfates, gold nanoparticles, biofilm alteration and removal, nitric oxide, polymeric biomaterials, polyhexamethylene biguanide, chlorhexidine salts, silver and silver salts.

[00119] In some modalities, topical retinoids for regulating epithelial cell growth useful in the poloxamer gel compositions described herein include, but are not limited to, retinol, retinoic acid, alitretinoin, isotretinoin, acitretin, adapalene, bexarotene, tazarotene, and retinoic acid derivatives.

[00120] In some formulations, the useful vaginal active agents in the poloxamer gel compositions described herein include, but are not limited to, clotrimazole, miconazole nitrate, nonoxynol-9, dequalinium chloride, imiquimod, and hydrocortisone. Examples

[00121] Various modalities will be further clarified by the following examples.

[00122] All formulations were prepared as received using poloxamer and viscosity-enhancing agents, including monoalkyl glycols, monoalkyl glycerols, and monoacyl glycerols from the manufacturers listed in Table 1. Since the surfactant is heat-sensitive and increases viscosity to form a non-fluid gel at a specific concentration and temperature, its colloidal solution-gel temperature was used as a positive control in comparing the C6, C8, C12, and C16 vicinal diols of this description at concentrations of 0.1 wt., 0.3 wt., 0.6 wt., 0.9 wt., 1.2 wt., 1.5 wt., and 1.8 wt. The concentration of poloxamer 407 was chosen as 17% by weight, with an average colloidal-gel solution temperature of 29.7°C. The concentration of poloxamer 188 was chosen at 46% by weight, with an average colloidal-gel solution temperature of 29°C.

[00123] Table 1 List of Neighboring Ingredients of Diol and Poloxamers Cx Company Name Lot No. C6diol Hexanediol Center for Innovative Drug Discovery SM2018-86-76 C6 ether Hexylglycerol Sigma Aldrich STBG2429V Octanediol Sigma Aldrich STBH118 6 Cfiether Octyl Glycerol Center for Innovative Drug Discovery SM2018-86-74 C8 ether Ethylhexyl Glycerol Schulke & Mayr 1272204 C8 ester 1-octanoyl-rac-glycerol Sigma Aldrich SLBW6117 C:2dio2 Dodecanediol Sigma Aldrich STB1186 C12 or L er 1-O-Dodecyl-rac-glycerol Biotechnology Santa Cruz H1911 Ci2esíer Lauricidin Med-Chem Laboratories 401060842 2 C16dicl Hexadecanediol TCI I43VI-EN C ] 6 ether 1-0-hexadecyl- rac-glycerol ChemCruz C1419 C16 ester Monopalmitin TCI HEX01- QTME C3 Poloxamer 407 Spectrum 2HA0214 and 1HH0918 Co Poloxamer 188 BASF WPYJ544B

[00124] Table 2 List of added suspended or dissolved ingredients: 15 Company Name Lot No. 1 EDTA Spectrum IDK0688 2 Guar Sigma SLBH5231V 3 PEG Sigma MKBH6594V 4 Avobenzene Merck 5844G124313 5 Lidocaine Topicaine 19671 6 PHMB Lonza 14GR100230 7 Zinc Oxide Spectrum 1GG0274 20 8 Miconazole Nitrate Sigma BCBD5966V 9 Terbinafine Sigma SLBR5903V 10 Acetylsalicylic Acid Spectrum 2GC0115 11 Medihoney DermaSciences WPYJ544B 12 Silver Sulfadiazine Sigma Aldrich MKBP8119V 13 Amylase Deerland 133806

[00125] Each of the vicinal diols studied has multiple chemical names. Therefore, to facilitate the representation of the various hydrophobic vicinal diols, which are represented by the symbols Ce, Ca, Cia, and Cie, with Csdio, CaeLe, and Cgeste representing 8-carbon monoalkyl glycols, monoalkyl glycerols, and monoacyl glycerols, respectively, and Ci2dioi, Cizeter, and Cizester representing 12-carbon monoalkyl glycols, monoalkyl glycerols, and monoacyl glycerols, respectively. The same terminology is used for the proximal diols Ce and Cie. The poloxamers studied are Poloxamer 407, also known as Pluronic® F-127, and Poloxamer 188, also known as Kolliphor® P 188 and Pluronic® F-68. Measurement of colloidal solution-gel transitions:

[00126] Colloidal-gel transition temperatures were determined by a test tube inversion method with a temperature increase of 1 °C per step. Aqueous poloxamer solutions (0.5 g) were prepared in 4 mL vials with an internal diameter of 11 mm. The vials were immersed in a water bath for 15 minutes at each step. The colloidal-gel transition temperature was monitored by inverting the vials, and if there was no flow within 30 seconds, it was considered a gel. The transition temperature was determined to an accuracy of ±1 °C.

[00127] Colloidal gel solution samples and temperatures were prepared and analyzed. The data show that the addition of monoalkyl glycols, monoalkyl glycerols, and monoacyl glycerols can affect the colloidal gel solution temperatures of both specific poloxamers and other poloxamers. Table 3 shows that octyl glycerol, in this case, decreases the overall colloidal gel solution temperature of 46% poloxamer 188 by approximately 5 °C at the concentrations used, while it decreases the colloidal gel solution temperature of 17% poloxamer 407 by up to 10 °C. This shows that Cge-er monoalkyl glycerols are able to lower the colloidal-gel solution temperatures of both the more hydrophobic poloxamers (such as poloxamer 407, HLB 22) and the more hydrophilic poloxamers (such as poloxamer 188, HLB 29) based on HLB values.

[00128] Table 3 Changes in colloidal-gel solution temperatures of both Poloxamer 407 and Poloxamer 188 in the presence of octyl glycerol (Ca^cr) at concentrations 0.1-2% P· Octyl glycerol (% by weight) 0 0 . 1 0.3 0.6 0 . 9 1 . 2 Poloxamer 188 at 46% Average Temperature of Colloidal-Gel Solution (°C) 29.0 25.0 22.2 24.0 24.2 24.0 Stdev 1.0 0.0 0.3 0.0 0.6 0.0 Poloxamer 407 at 17% Average Temperature of Colloidal-Gel Solution (°C) 29.7 24.7 22.3 21.5 20.0 19.7 Stdev 0.3 0.3 0.3 0.0 0.0 0.3 Sample preparation

[00129] The samples were prepared using the bill of materials in Table 1.

[00130] Six and eight carbon chains (Ce and Cs): 10 mL of each sample of Códioi, Cecter, Ctjdiclz Cseterz Or Cgester 6P were prepared at the above weight percentiles using water as the diluent. The calculated amount of water was weighed and placed in a beaker. The beaker was placed in an ice bath (approximately 13–15 °C) and the desired weight percent of surfactant Poloxamer 407 or Poloxamer 188 was added and stirred until completely dissolved. Monoalkyl glycol Ce or Ce, monoalkyl glycerol, or monoacyl glycerol was placed in the beaker and stirred slowly. The beaker was removed from the ice bath and placed on a stirring plate with continuous stirring at RTP until the vicinal diols were completely dissolved. The composition was then placed in a disposable test tube where it could form a gel at room temperature.

[00131] Twelve and sixteen carbon chains (Cm and Cu): 10 mL of each sample of Cizdioi, Cizeter, Cizester, Cudici, Ciéeter, or Cuester were prepared at the above weight percentages using water as a diluent. The calculated amount of water was weighed and placed in a beaker, then the desired weight percent of monoacylglycerol, monoalkyl ether of glycerol, or monoacylglycerol was placed in the beaker along with 1 / 3 of the weighed 17% surfactant and stirred at 50–70°C to allow complete solvation. The temperature was turned off, the beaker was placed in an ice bath, and the remaining 2 / 3 of the 17% surfactant was added and stirred until complete dissolution. The composition was then placed in a disposable test tube where it could form a gel at room temperature.

[00132] Figure 1 shows the colloidal-gel solution temperature results for compositions made as specified, using Ce vicinal diols, which also show the indirect relationship between the colloidal-gel solution temperature of Poloxamer 407 with increasing amounts of 6-carbon monoalkyl glycol or monoalkyl glycerol.

[00133] An overall temperature drop of 1.5 °C and 2.7 °C was observed following the addition of hexanediol and hexyglycerol, respectively. This illustrates the ability of 6-carbon vicinal diols to lower the colloidal-gel solution temperature of Poloxamer 4 07.

[00134] Figure 2 shows the colloidal gel temperature results using Poloxamer 407 with increasing amounts of monoalkyl glycol Cs, monoalkyl glycerol, and monoacyl glycerol. The 17 wt% positive control, the Poloxamer 407 sample, is represented by the highest point on the graph, showing an average colloidal gel temperature of 29.7 °C (from three readings). After the addition of 0.1% octanediol, octyl glycerol, and octanoylglycerol, an initial sharp decrease in the colloidal gel temperature of approximately 56 °C was observed for each vicinal diol Cg tested. In general, the colloidal-gel solution temperature continued to decrease gradually as the wt% of monoalkyl glycerol, monoacyl glycerol or Cs monoalkyl glycol increased, after the initial drop of 5-6 °C.

[00135] Figure 3 shows the colloidal-gel temperature results using Poloxamer 407 with increasing amounts of added monoalkyl Cu glycol, monoalkyl glycerol, and monoacyl glycerol. As in Figures 1 and 2, the positive control of Poloxamer 407 alone (without added vicinal diol) is represented by the highest point on the graph, showing an average colloidal-gel temperature of 29.7 °C. Similar to the Ce vicinal diols, after the addition of 0.1% dodecanediol, dodecyl-l-glycerol, and 5-dodecanoyl-l-glycerol, a sharp decrease in the colloidal-gel temperature of approximately 57 °C was found for each Cíe vicinal diol tested. In general, the t temperature of the colloidal-gel solution continued to decrease gradually as the wt% of monoalkyl glycol 10 Ci?, monoalkyl glycerol or monoacyl glycerol increased, after the initial drop of 5-7 °C.

[00136] Therefore, it is observed that the average colloidal-gel solution temperature of poloxamer 407 can be lowered to 7°C with only 0.1 wt% vicinal diol, with a maximum apparent decrease of 10-120C.

[00137] Figure 4 shows normalized data for vicinal diols with 8-carbons to 16-carbons. The data were normalized using the colloidal gel solution temperatures of poloxamer 407 in each formulation. Therefore, the initial reading of one (1) corresponds to the positive control (poloxamer without added vicinal diol (C1)). The colloidal gel solution temperature of Poloxamer 407 initially decreased by approximately 5 °C with the addition of 0.1 wt.% C5 and C12 proximal diols. In addition, there is an overall decrease of approximately 10 °C in the colloidal gel solution temperature of Poloxamer 407 when C5 and C12 are present at 1.8 wt. The initial decrease in the colloidal gel solution temperature of C12 vicinal diols was approximately 2 °C, while the overall decrease to 1.An 8 wt% concentration results in approximately 3 °C, which is similar to the effect of vicinal diols C6, indicating that the 8 and 12 carbons are more effective at reducing colloidal-gel temperatures than the 6 or 16 carbons. However, the addition of C1 or C12 still imparts a decrease in colloidal-gel temperature; therefore, all vicinal diols (C6 to C1) are effective at reducing the colloidal-gel temperatures of poloxamers, such as Poloxamer 407, with C1 and C12 being the most effective. Determination of Colloidal-Gel Solution using the Drop Flow Method

[00138] The determination of whether a colloidal gel solution formed was performed by pipetting 0.24 g of poloxamer gel composition onto a glass surface tilted at an approximate 90° angle. Using a black marking pen, the glass surface was scored in 0.5 cm lines to determine the distance over which the poloxamer gel composition would flow down the glass surface at room temperature (23.5 °C). The pipetted poloxamer gel composition was deposited as a circular drop at the highest elevation (just above the line for 0 cm). Readings were taken at 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, and 60 minutes. The readings of 0 cm at 60 minutes indicated that there was no flow from the poloxamer gel composition and therefore the composition was above its colloidal solution-gel temperature and was considered to be a gel.Readings of 6 cm at 0 minutes (immediate flow) indicate that the composition flowed easily and was therefore below its colloidal-gel solution temperature and was considered to be a liquid.

[00139] Samples and colloidal gel solution temperatures were prepared and analyzed using either a linear glycerol (octylglycerol) or a branched glycerol (ethylhexylglycerol). The data show that the addition of a linear or branched vicinal diol can affect the colloidal gel solution temperature of poloxamer gel compositions. Figure 5 shows that the addition of octylglycerol or ethylhexylglycerol to 17% Poloxamer 407 results in a non-flowing gel, while 17% Poloxamer 407 alone flows across the entire 6 cm² regulated glass surface. The results are the same at all time points between immediate (zero minutes) and 60 minutes. In other words, 17% Poloxamer 407 flows immediately to the full length of the glass surface (6 cm) and poloxamer gel compositions containing vicinal diols are non-flowing gels at any time evaluated. Sample preparation

[00140] The samples were prepared using the bill of materials in Table 1.

[00141] Each sample was prepared using water as the diluent. The calculated amount of water was weighed and placed in a beaker. The beaker was placed in an ice bath (approximately 13–15 °C) and 17 wt% Poloxamer 407 surfactant was added and stirred until completely dissolved. 0.9 wt% Ce monoalkyl glycerols, either octyl glycerol or ethylhexyl glycerol, were placed in the beaker and stirred slowly. The beaker was removed from the ice bath and placed on a stirring plate with continuous stirring at RTP (room temperature and pressure) until the vicinal diols were completely dissolved.

[00142] Figure 5 shows the results of the colloidal solution-gel determination using the drop-flow method. At room temperature, 17% poloxamer 407 alone is a solution, while the addition of a linear or nonlinear vicinal diol to the poloxamer resulted in a gel. Therefore, this additional measurement method (drop-flow) also indicates the effect of vicinal diols, including branched vicinal diols, on lowering the colloidal solution-gel temperature of poloxamers.

[00143] It is important to note that lowering the temperature of the colloidal solution-gel causes the gel to behave even further below body temperature with the same amount of poloxamer. This allows for the creation of compositions with a longer residence time on a biological surface, so that a biologically active agent in the gelled poloxamer can be effectively delivered to the biological surface requiring treatment over an extended period.

[00144] Table 2 lists several active agents that can be suspended or dissolved in a 17 wt% Poloxamer 407 copper diol (Cuestor) solution. These active agents include: Pharmaceutical Agent: Acetylsalicylic acid Wound healing agent: Manuka honey Enzymatic agent: Amylase Antimicrobial agent: PHMB, Miconazole Nitrate, Terbinafine Anti-itch agent: Lidocaine Anti-scald agent: Silver sulfadiazine Chelating agent: EDTA (ethylenediaminetetraacetic acid) Hydrophilic Polymer: Guar UV Absorbing Agent: Avobenzene, Zinc Oxide

[00145] Observations were made when various weight percentages of active agents were added to 17% poloxamer 407 + 0.9% dodecanediol gel. The results after 24 hours are reported in Table 4 below.

[00146] Table 4. Active Agents and Observations Number Name Observation 1 0.5% EDTA gel 2 0.5% Guar gel 3 3% Avobenzone gel 4 5% Lidocaine gel 5 0.1% PHMB gel 6 1% PHMB gel 7 20% Zinc Oxide suspension, gel 8 2% Miconazole nitrate suspension, gel 9 0.5% Terbinafine gel 10 1% Acetylsalicylic acid gel 11 10% Medihoney gel 12 1% Silver sulfadiazine suspension, gel 13 10% Am i lasa gel suspension

[00147] Each of these formulations demonstrated stability for at least 24 hours as indicated in Table 4. It is worth noting that even the suspensions were stable for at least 24 hours. Specific Modalities

[00148] In a first specific embodiment, a poloxamer gel composition is described. The poloxamer gel composition includes from 0.05 to 5 wt% of a hydrophobic vicinal diol component; and from 10 to 65 wt% of a poloxamer component, wherein the hydrophobic vicinal diol component is monoalkyl glycols of 6 to 16 carbons in length, monoalkyl glycerols, monoacyl glycerols, or a combination thereof, and wherein the hydrophobic vicinal diol component lowers a colloidal-gel solution temperature of the aqueous poloxamer equivalent by at least 1°C.

[00149] A second specific embodiment includes the first specific embodiment wherein the poloxamer component comprises a poloxamer selected from the group consisting of Poloxamer 108, Poloxamer 124, Poloxamer 188, Poloxamer 127, Poloxamer 237, Poloxamer 238, Poloxamer 288, Poloxamer 335, Poloxamer 338, Poloxamer 407, or combinations thereof.

[00150] A third specific embodiment includes any of the first to second specific embodiments wherein the hydrophobic vicinal diol component comprises a hydrophobic monoalkyl glycol having a structure of formula 1: on no R, formula 1, where R = branched or unbranched Ce-Cio alkyl group or alkyl group.

[00151] A fourth specific modality includes the third specific modality where the hydrophobic monoaquinotic glycol is selected from the group consisting of 1,2-hexanediol, 1,2-octanediol, 1,2-nonanediol, 1,2-decanediol, 1,2-undecanediol, 1,2-dodecanediol, 1,2-tridecanediol, 1,2-tetradecanediol, 1,2-pentadecanediol, 1,2-hexadecanediol and combinations thereof.

[00152] A fifth specific embodiment includes any of the first to the fourth specific embodiment wherein the hydrophobic vicinal diol component comprises a hydrophobic monoalkyl glycerol having a structure of formula 2: , formula 2, where R = branched or unbranched alkyl group or C₆C₆ alkyl group.

[00153] A sixth specific modality includes the fifth specific modality where the hydrophobic monoalkyl glycol is selected from the group consisting of glycerol-1 hexyl ether, glycerol-l-heptyl ether, glycerol-l-octyl ether, glycerol-1-(2-ethylhexyl) ether (also known as octoxyglycerin, 2-ethylhexylglycerin, 3-(2-ethylhexyloxy)propane-1,2-diol and Sensiva® SC SC SC 50), glycerol-l-nonyl ether, glycerol-l-decyl ether, glyceryl-1 undecyl ether, glycerol-1-dodecyl ether, glycerol-l-tridecyl ether, glycerol-l-tetradecyl ether, glycerol-l-pentadecyl ether and glycerol-hexadecyl ether, and combinations thereof.

[00154] A seventh specific embodiment includes any of the first through sixth specific embodiments wherein the hydrophobic vicinal diol component comprises a hydrophobic monoacylglycerol Oli which has a structure of formula 3:r, formula 3, where R = branched or unbranched alkyl group or Có-C:e alkyl group.

[00155] An eighth specific embodiment includes the seventh specific embodiment where the hydrophobic monoacylglycerol is selected from the group consisting of glycerol monohexanoate, glycerol monooctanoate, glycerol monononanoate, glycerol monodecanoate, glycerol monoundecanoate, glycerol monododecanoate, glycerol monotridecanoate, glycerol monotetradecanoate, glycerol monopentadecanoate, glycerol monohexadecanoate and combinations thereof.

[00156] A ninth specific modality includes any of the first through fourth specific modalities where the composition is aqueous.

[00157] A tenth specific modality includes any of the first through ninth specific modalities wherein the hydrophobic vicinal diol component lowers a colloidal-gel solution temperature of the aqueous poloxamer equivalent by at least 3 °C.

[00158] An eleventh specific modality includes the tenth specific modality where the colloidal gel solution temperature of the aqueous poloxamer equivalent is at least 26.5 °C.

[00159] A twelfth specific embodiment includes any of the first through eleventh specific embodiments wherein the aqueous poloxamer gel composition further comprises a solubilized or suspended silver salt, silver nanoparticle, zinc nanoparticle, zinc salt, calcium salt, gold salt, gold nanoparticle, magnesium nanoparticle salt, titanium nanoparticle salt, phosphorus compound, siloxy compound, iodine compound, barium salt, cerium compound, cobalt compound, copper compound, iron compound, manganese compound, nickel compound, strontium compound, or a combination thereof.

[00160] A thirteenth specific modality includes any of the first through twelfth specific modality wherein the poloxamer gel composition further comprises a biologically active agent, solubilized or suspended, wherein the biologically active agent is an antibiotic, antimicrobial agent, antifungal agent, antiviral agent, antibacterial agent, antiacne agent, antiallergic, psoriasis agent, analgesic, anesthetic, anticoagulant, antihistamine, antiprotozoal agent, antiparasitic agent, antipruritic agent, arthritis agent, astringent, anorectal agent, anti-inflammatory agent, antimitotic, antiperspirant, chelating agent, deodorant, essential oil, eczema agent, antiseborrheic agent, cancer treatment agent, canker sore treatment agent, cold sore treatment agent, corticosteroid, cytokine, dental agent, depigmenting agent, diaper rash treatment agent, hormone endocrine, enzyme,glycolipid, immune response modifier, keratolytic agent, joint pain agent, hair growth stimulant, heat shock protein, glycoprotein, growth factor, growth hormone, hemostatic, lipid, moisturizer, nasal active, nonsteroidal anti-inflammatory drug (NSAID), protein, peptide, pediculicide, periodontal treatment agent, nucleic acid, protease inhibitor, photosensitizing active, polysaccharide, retinoid, rosacea agent, skin barrier / protectant, skin treatment agent, saccharide, scabicide, spheroid, sunburn treatment agent, sunscreen, thermal and radiation burn treatment agent, transdermal active, vaginal active, vasoconstrictor, vasodilator, vitamin, wart treatment agent, wart removal agent, wound debridement agent, wound treatment agent, wound healing agentantimicrobial wound agent or combination thereof.

[00161] A fourteenth specific embodiment includes any of the first through thirteenth specific embodiments wherein the poloxamer gel composition further comprises a water-soluble polymer selected from the group consisting of aloe vera, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, polyquaternium-1, polyquaternium-6, polyquaternium-10, guar, hydroxypropylguar, hydroxypropylmethylguar, cationic guar, carboxymethylguar, maltodextrin, hydroxymethylchitosan, hydroxypropylchitosan, carboxymethylchitosan, N-[(2-hydroxy-3-trimethylammonium chloride)propyl]chitosan, water-soluble chitosan, hyaluronic acid and its salts, chondroitin sulfate, heparin, dermatan sulfate, amylose, amylopectin, pectin, gum carob, alginate, dextran, carrageenan, xanthan gum, gellan gum, scleroglucan, schizophyllan, gum arabic, ghatti gum, karaya gum, tragacanth gum, pectins, starch and its derivatives,tamarind gum, poly(vinyl alcohol), poly(ethylene oxide), poly(ethylene glycol), poly(methyl 1-vinyl 1-ether), polyacrylamide, poly(N,N-dimethylacrylamide), poly(N-vinylacetamide), poly(N-vinylformamide), poly(2-hydroxyethyl methacrylate), poly(glyceryl methacrylate), poly(N-vinylpyrrolidone), poly(dimethylaminoethyl methacrylate), poly(dimethylaminopropyl acrylamide), polyvinylamine, poly(diyldimethylammonium chloride), poly(isopropylacrylamide), poly(N-vinylcaprolactam) and combinations thereof, provided that gel formation is maintained.

[00162] A fifteenth specific embodiment includes any of the first through fourteenth specific embodiments wherein the poloxamer gel composition further comprises an antimicrobial agent, wherein the antimicrobial agent is a chlorhexidine salt, alexidine salt, poly(hexamethylenebiguanide) salt, benzalkonium salt, benzethonium salt, cetyltrimethylammonium salt, cetylpyridinium salt, didocedyldimethylammonium salt,N-heptyl-N-dodecylpiperidinium bromide, N-hexyl-N-dodecylpiperidinium bromide, glyceryl monolaurate, sorbic acid, or combinations thereof.

[00163] A sixteenth specific embodiment relates to a method for reducing the colloidal-gel solution temperature of a poloxamer gel composition by at least 3 °C, comprising: adding 0.1 to 1.8 wt% of a hydrophobic vicinal diol component to the aqueous poloxamer gel composition, wherein the hydrophobic vicinal diol component is monoalkyl glycols, monoalkyl glycerols, monoacyl glycerols with a carbon chain length of 6 to 16 carbons, or a combination thereof.

[00164] A specific seventeenth embodiment includes the sixteenth embodiment where the vicinal hydrophobic diol component comprises hydrophobic monoalkyl glycols, monoalkyl glycerols, and monoacyl glycerols; wherein the hydrophobic substituents are aliphatic, linear or branched, and saturated or unsaturated.

[00165] An eighteenth specific embodiment includes any of the sixteenth to seventeenth specific embodiments wherein the hydrophobic vicinal diol component comprises a hydrophobic monoalkyl glycol having a OH HO formula 1: R, formula 1 structure, wherein R = branched or unbranched Cé-Cie alkyl group or alkyl group.

[00166] A nineteenth specific embodiment includes any of the sixteenth to eighteenth specific embodiments wherein the hydrophobic vicinal diol component comprises a hydrophobic monoalkyl glycerol having a structure of formula 2: OH formula 2, where R = alkylene group or C6-C16 branched or unbranched alkyl group.

[00167] A twentieth specific modality includes any of the sixteenth to nineteenth specific modality wherein the hydrophobic vicinal diol component comprises a hydrophobic monoacyl glycerol having a structure of formula 3: OH not o—y R, formula 3, where R = branched or unbranched C6-C16 alkyl group or alkyl group.

[00168] A twenty-first specific embodiment includes any of the sixteenth to twentieth specific embodiments wherein the poloxamer gel composition further comprises an active ingredient selected from the group consisting of at least 0.4% EDTA, at least 0.4% guar gum, at least 2% avobenzene, at least 2.5% lidocaine, 0.1% to 1% PHMB, at least 10% zinc oxide, at least 1% miconazole nitrate, at least 0.4% terbinafine, at least 0.5% acetylsalicylic acid, at least 5% Medihoney, at least 0.5% silver sulfadiazine, at least 0.5% amylase, and combinations thereof.

[00169] Although the preceding descriptive memorandum contains many specific details, these should not be construed as limitations on the scope of the description, but rather as examples of preferred embodiments thereof. Many other variations are possible. Accordingly, the scope of the description shall be determined not by the embodiments illustrated, but by the appended claims and their statutory equivalents.

Claims

1. A poloxamer gel composition comprising: from 0.05 to 5 wt% of a hydrophobic vicinal diol component; and from 10 to 65 wt% of a poloxamer component, wherein the hydrophobic vicinal diol component is monoalkyl glycols, monoalkyl glycerols, monoacyl glycerols of 6 to 16 carbons in length, or a combination thereof, and wherein the hydrophobic vicinal diol component lowers a colloidal-gel solution temperature of the aqueous poloxamer equivalent by at least 1 °C.

2. The poloxamer gel composition of claim 1, wherein the poloxamer component comprises a poloxamer selected from the group consisting of Poloxamer 108, Poloxamer 124, Poloxamer 188, Poloxamer 127, Poloxamer 237, Poloxamer 238, Poloxamer 288, Poloxamer 335, Poloxamer 338, Poloxamer 407 or combinations thereof.

3. The poloxamer gel composition of claim 1, wherein the hydrophobic vicinal diol component comprises a hydrophobic monoalkyl glycol having a structure of formula 1: OH formula 1, wherein R = branched or unbranched Cg-C-alkyl group or Cg-C-alkyl group.

4. The poloxamer gel composition of claim 3, wherein the hydrophobic monoalkyl glycol is selected from the group consisting of 1,2-hexanediol, 1,2-octanediol, 1,2-nonanediol, 1,2-decanediol, 1,2-undecanediol, 1,2-dodecanediol, 1,2-tridecanediol, 1,2-tetradecanediol, 1,2-pentadecanediol, 1,2-hexadecanediol and combinations thereof.

5. The poloxamer gel composition of claim 1, wherein the hydrophobic vicinal diol component comprises a hydrophobic monoalkyl glycerol having a structure of formula 2: OH no or formula 2, wherein R = branched or unbranched Cg-C-alkyl group or alkyl group. 7 0 6. The poloxamer gel composition of claim 5, wherein the hydrophobic monoalkyl glycol is selected from the group consisting of glycerol-1-hexyl ether, glycerol-1-heptyl ether, glycerol-1-octyl ether, glycerol-1-(2-ethylhexyl) ether (also known as octoxyglycerin, 2-ethylhexylglycerin, 3-(2-ethylhexyloxy)propane-1,2-diol, and Sensiva® SC SC 50), glycerol-1-nonyl ether, glycerol-1-decyl ether, glyceryl-1-undecyl ether, glycerol-1-dodecyl ether, glycerol-1-tridecyl ether, glycerol-1-tetradecyl ether, glycerol-1-pentadecyl ether, and glycerol-hexadecyl ether, and combinations thereof.

7. The poloxamer gel composition of claim 1, wherein the hydrophobic vicinal diol component comprises a hydrophobic monoacyl glycerol having a structure of formula 3: <>n HO O-«formula 3, wherein R = branched or unbranched Ce-Cu alkyl group or alkyl group.

8. The poloxamer gel composition of claim 7, wherein the hydrophobic monoacyl glycerol is selected from the group consisting of glycerol monohexanoate, glycerol monooctanoate, glycerol mononononanoate, glycerol monodecanoate, glycerol monododecanoate, glycerol monotridecanoate, glycerol monotetradecanoate, glycerol monopentadecanoate, glycerol monohexadecanoate, and combinations thereof.

9. The poloxamer gel composition of claim 1, wherein the composition is aqueous.

10. The poloxamer gel composition of claim 1, wherein the hydrophobic vicinal diol component lowers a colloidal-gel solution temperature of the aqueous poloxamer equivalent by at least 3 °C.

11. The poloxamer gel composition of claim 10, wherein the colloidal-gel solution temperature of the aqueous poloxamer equivalent is at least 26.5 °C.

12. The poloxamer gel composition of claim 1, wherein the aqueous poloxamer gel composition further comprises a solubilized or suspended silver salt, silver nanoparticle, zinc nanoparticle, zinc salt, calcium salt, gold salt, gold nanoparticle, magnesium nanoparticle salt, titanium nanoparticle salt, phosphorus compound, siloxy compound, iodine compound, barium salt, cerium compound, cobalt compound, copper compound, iron compound, manganese compound, nickel compound, strontium compound, or a combination thereof.

13. The poloxamer gel composition of claim 1, wherein the poloxamer gel composition further comprises a biologically active agent, solubilized or suspended, wherein the biologically active agent is an antibiotic, antimicrobial agent, antifungal agent, antiviral agent, antibacterial agent, antiacne agent, antiallergic agent, psoriasis agent, analgesic, anesthetic, coagulant agent, antihistamine, antiprotozoal agent, antiparasitic agent, antipruritic agent, arthritis agent, astringent, anorectal agent, anti-inflammatory agent, antimitotic agent, antiperspirant, chelating agent, deodorant, essential oil, eczema agent, antiseborrheic agent, cancer treatment agent, oral aphthous ulcer treatment agent, cold sore treatment agent, corticosteroid, cytokine, dental agent, depigmenting agent, diaper rash treatment agent, endocrine hormone, enzyme, glycolipid,immune response modifier, keratolytic agent, joint pain agent, hair growth stimulant, heat shock protein, glycoprotein, growth factor, growth hormone, hemostatic, lipid, moisturizer, nasal active, nonsteroidal anti-inflammatory drug (NSAID), protein, peptide, pediculicide, periodontal treatment agent, nucleic acid, protease inhibitor, phosphatidylsensitizing active, polysaccharide, retinoid, rosacea agent, skin barrier / protectant, skin treatment agent, saccharide, scabicide, spheroid, sunburn treatment agent, sunscreen, thermal and radiation burn treatment agent, transdermal active, vaginal active, vasoconstrictor, vasodilator, vitamin, wart treatment agent, wart removal agent, wound debridement agent, wound treatment agent, wound healing agentantimicrobial wound agent or combination thereof.

14. The poloxamer gel composition of claim 1, wherein the poloxamer gel composition further comprises a water-soluble polymer selected from the group consisting of aloe vera, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, polyquaternium-1, polyquaternium-6, polyquaternium-10, guar, hydroxypropylguar, hydroxypropylmethylguar, cationic guar, carboxymethylguar, maltodextrin, hydroxymethylchitosan, hydroxypropylchitosan, carboxymethylchitosan, N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan chloride, water-soluble chitosan, hyaluronic acid and its salts, chondroitin sulfate, heparin, dermatan sulfate, amylose, amylopectin, pectin, locust bean gum, alginate, dextran, carrageenan, xanthan gum, gellan gum, scleroglucan, schizophyllan, gum arabic, ghatti gum, karaya gum, tragacanth gum, pectins, starch and its derivatives, tamarind gum, poly(vinyl alcohol), poly(ethylene oxide),poly(ethylene glycol), poly(methyl-1-vinyl-1-ether), polyacrylamide, poly(N,N-dimethylacrylamide), poly(N-vinylacetamide), poly(N-vinyl-1-formamide), poly(2-hydroxyethyl methacrylate), poly(glyceryl methacrylate), poly(N-vinylpyrrolidone), poly(dimethylaminoethyl methacrylate), poly(dimethylaminopropylacrylamide), polyvinylamine, poly(diallyldimethylammonium chloride), poly(isopropylacrylamide), poly(N-vinylcaprolactam) and combinations thereof, provided that gel formation is maintained.

15. The poloxamer gel composition of claim 1, wherein the poloxamer gel composition further comprises an antimicrobial agent, the antimicrobial agent being a chlorhexidine salt, alexidine salt, poly(hexamethylenebiguanide) salt, benzalkonium salt, benzethonium salt, cetyltrimethylammonium salt, cetylpyridinium salt, didodecyldimethylammonium salt, N-heptyl-N-dodecylpiperidinium bromide, N-hexyl-N-dodecylpiperidinium bromide, glyceryl monolaurate, sorbic acid, or combinations thereof.

16. A method for lowering the colloidal-gel solution temperature of a poloxamer gel composition by at least 3 °C, comprising: adding 0.1 to 1.8 wt% of a hydrophobic vicinal diol component to the aqueous poloxamer gel composition, wherein the hydrophobic vicinal diol component is monoalkyl glycols, monoalkyl glycerols, monoacyl glycerols of 6 to 16 carbons or a combination thereof.

17. The method according to claim 16, wherein the hydrophobic vicinal diol component comprises hydrophobic monoalkyl glycols, monoalkyl glycerols, and monoacyl glycerols, and wherein the hydrophobic substituents are aliphatic, linear or branched, and saturated or unsaturated.

18. The method according to claim 16, wherein the hydrophobic vicinal diol component comprises a hydrophobic monoalkyl glycol having a structure of formula 1: wherein R = branched or unbranched C6-C16 alkyl group or alkyl group. 10 19. The method according to claim 16, wherein the hydrophobic vicinal diol component comprises a hydrophobic monoalkyl glycerol having a structure of formula 2: OH ho. ,o 15 R formula 2, wherein R = branched or unbranched C6-C16 alkyl group or alkyl group.

20. The method according to claim 16, wherein the hydrophobic vicinal diol component comprises a hydrophobic monoacyl glycerol having a structure of formula 3: OH HO O-oc r formula 3, wherein R = branched or unbranched C6-C16 alkyl group or alkyl group.

21. The method according to claim 1, wherein the poloxamer gel composition further comprises an active ingredient selected from the group consisting of at least 0.4% EDTA, at least 0.4% guar gum, at least 2% avobenzene, at least 2.5% lidocaine, 0.1% to 1% PHMB, at least 10% zinc oxide, at least 1% miconazole nitrate, at least 0.4% terbinafine, at least 0.5% acetylsalicylic acid, at least 5% Medihoney, at least 0.5% silver sulfadiazine, at least 0.5% amylase, and combinations thereof.