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CA-3155909-C - POLOXAMER COMPOSITIONS WITH REDUCED SOL-GEL TRANSITION TEMPERATURES AND METHODS OF REDUCING THE SOL-GEL TRANSITION TEMPERATURE OF POLOXAMER COMPOSITIONS

CA3155909CCA 3155909 CCA3155909 CCA 3155909CCA-3155909-C

Abstract

The reduction in the sol-gel temperature of aqueous poloxamer surfactant compositions by the addition of hydrophobic vicinal diols is provided. Lowering of the sol-gel temperature and the gelling efficiency of water-soluble poloxamer block copolymers of polyethylene oxide-b- polypropylene oxide-b-polyethylene oxide has been markedly improved by the addition of small amounts of at least one hydrophobic vicinal diol, such as monoalkyl glycols, monoalkyl glycerols, or monoacyl glycerols. The decrease in the sol-gel temperature facilitates gel formation, and such gels exhibit greater residence time on a surface, particularly those with biological properties.

Inventors

  • Joseph C. Salamone
  • Rebecca Erin McMahon
  • Suprena Emanuella Zariah Poleon
  • ANN BEAL SALAMONE

Assignees

  • ROCHAL TECHNOLOGIES, LLC

Dates

Publication Date
20260505
Application Date
20201021
Priority Date
20191028

Claims (20)

  1. CLAIMS 1. A poloxamer gel composition comprising: 0.05 to 5 wt. % hydrophobic vicinal diol component; and 10 to 65 wt. % of a poloxamer component, wherein the hydrophobic vicinal diol component is 6-carbon to 16-carbon length monoalkyl glycols, monoalk:yl glycerols, monoacyl glycerols, or a combination thereof, and wherein the hydrophobic vicinal diol component depresses a sol-gel temperature of the aqueous poloxamer equivalent by at least 1 °C.
  2. 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, and combinations thereof.
  3. 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 HO~R formula 1, wherein R = C6-Ct6 branched or unbranched alkyl group or alkylene group.
  4. 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. 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 HO~O'---R formula 2, wherein R = C6-Ct6 branched or unbranched alkyl group or alkylene group. 36 Date Re9ue/Date Received 2024-04-11
  6. 6. The poloxamer gel composition of claim 5, wherein the hydrophobic monoalk:yl 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-ethylhexyl glycerin, 3-(2-ethylhexyloxy)propane-l,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, glycerol 1-hexadecyl ether, and combinations thereof.
  7. 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: ~c HO 0-< R formula 3, wherein R = C6-C16 branched or unbranched alkyl group or alk:ylene group.
  8. 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 monononanoate, glycerol monodecanoate, glycerol monoundecanoate, glycerol monododecanoate, glycerol monotridecanoate, glycerol monotetradecanoate, glycerol monopentadecanoate, glycerol monohexadecanoate, and combinations thereof.
  9. 9. The poloxamer gel composition of claim 1, wherein the composition is aqueous.
  10. 10. The poloxamer gel composition of claim 1, wherein the hydrophobic vicinal diol component depresses a sol-gel temperature of the aqueous poloxamer equivalent by at least 3°C.
  11. 11. The poloxamer gel composition of claim 10, wherein the sol-gel temperature of the aqueous poloxamer equivalent is at least 26.5°C. 37 Date Re9ue/Date Received 2024-04-11
  12. 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, phosphorous compound, siloxy compound, iodine compound, barium salt, cerium compound, cobalt compound, copper compound, iron compound, manganese compound, nickel compound, strontium compound, or combination thereof.
  13. 13. The poloxamer gel composition of claim 1, wherein the poloxamer gel composition further comprises a biologically active agent, solubilized or suspended, the biologically active agent being an antibiotic, antimicrobial agent, antifungal agent, antiviral agent, antibacterial agent, anti-acne agent, anti-allergenic, psoriasis agent, analgesic, anesthetic, anticlotting agent, antihistamine, anti-protozoan agent, antiparasitic agent, antipruritic agent, arthritis agent, astringent, anorectal, 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, endocrine hormone, enzyme, glycolipid, immunological response modifier, keratolytic agent, joint pain agent, hair growth stimulant, heat shock protein, glycoprotein, growth factor, growth hormone, hemostatic, lipid, moisturizer, nasal active, non-steroidal anti-inflammatory drug (NSAID), protein, peptide, pediculicide, periodontal treatment agent, nucleic acid, protease inhibitor, photosensitizing active, polysaccharide, retinoid, rosacea agent, skin protectant/barrier agent, skin treatment agent, saccharide, scabicide, steroid, sunburn treatment agent, sunscreen, thermal and radiation burn treatment agent, transdermal active, vaginal active, vasoconstrictor, vasodilator, vitamin, wart treatment agent, wart removal agent, wound debriding agent, wound treatment agent, wound healing agent, wound antimicrobial agent, or combination thereof.
  14. 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, hydroxypropy lmethy lcellulose, carboxymethy lcellulose, polyquatemium-1, polyquatemium- 6, polyquatemium-10, guar, hydroxypropylguar, hydroxypropylmethylguar, cationic guar, carboxymethy lguar, maltodextrin, hydroxymethy lchitosan, hydroxypropy lchitosan, 38 Date Re9ue/Date Received 2024-04-11 carboxymethy lchitosan, N-[ (2-hydroxy-3-trimethy lammonium)propy 1 ]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, pectins, starch and its derivatives, 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-vinylpyrrolidone), poly( dimethylaminoethyl methacrylate ), poly( dimethylaminopropyl acrylamide ), polyvinylamine, poly(diallyldimethyammonium chloride), poly(N-isopropylacrylamide), poly(N-vinylcaprolactam), and combinations thereof, provided that gel formation is maintained.
  15. 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-Ndodecylpiperidinium bromide, glyceryl monolaurate, sorbic acid, or combinations thereof.
  16. 16. A method of lowering the sol-gel 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 6-carbon to 16-carbon length monoalkyl glycols, monoalkyl glycerols, monoacyl glycerols, or a combination thereof.
  17. 17. The method according to claim 16, wherein the hydrophobic vicinal diol component comprise hydrophobic monoalkyl glycols, monoalkyl glycerols, and monoacyl glycerols, and wherein the hydrophobic substituents are aliphatic, linear or branched, and saturated or unsaturated. 39 Date Re9ue/Date Received 2024-04-11
  18. 18. The method according to claim 16, wherein the hydrophobic vicinal diol component comprise a hydrophobic monoalky 1 glycol having a structure of formula 1: OH HO~R formula 1, wherein R = C6-Ct6 branched or unbranched alkyl group or alkylene group.
  19. 19. The method according to claim 16, wherein the hydrophobic vicinal diol component comprise a hydrophobic monoalkyl glycerol having a structure of formula 2: OH HO~O--.._R formula 2, wherein R = C6-Ct6 branched or unbranched alkyl group or alkylene group.
  20. 20. The method according to claim 16, wherein the hydrophobic vicinal diol component comprise a hydrophobic monoacyl glycerol having a structure of formula 3: ~c HO o-{ R formula 3, wherein R = C6-Ct6 branched or unbranched alkyl group or alkylene group.

Description

Poloxamer Compositions With Reduced Sol-Gel Transition Temperatures and Methods of Reducing the Sol-Gel Transition Temperature of Poloxamer Compositions FIELD OF INVENTION [0001] This disclosure relates generally to the reduction in the sol-gel temperature of aqueous poloxamer surfactant compositions by the addition of hydrophobic vicinal dials. The hydrophobic vicinal dials comprise monoalkyl glycols, monoalkyl glycerols, and monoacyl glycerols. The decrease in the sol-gel temperature facilitates a higher composition viscosity, wherein such higher viscosities allow greater residence time on a surface, particularly those of biological origin. BACKGROUND OF THE INVENTION [0002] Poloxamers are triblock copolymers of poly(ethylene oxide) and poly(propylene oxide) that have thermoreversible properties wherein they transform from a liquid-like behavior to gel-like behavior above a certain temperature and certain percent composition in aqueous systems. This phenomenon is termed the sol-gel transition, most often represented by the sol-gel transition temperature, Tsol-gel. The sol-gel transition can also be varied by certain excipients. By varying the concentration of poloxamer and other excipients, hydro gels with sol-gel transition point close to body temperature can be achieved. This transition is reversible by lowering the temperature, poloxamer concentration, or by changing excipients. [0003] The structure of the poloxamers are arranged usually as poly(ethylene oxide-copropylene oxide-co-ethylene oxide) or the reverse, poly(propylene oxide-co-ethylene oxide-copropylene oxide). Poloxamers generally appear as white, waxy, free-flowing surfactants. For water-soluble poloxamers, at low concentrations ( l 0-4 _ l 0-5 wt. % ) monomolecular micelles are formed, but higher concentrations result in multimolecular aggregates consisting of a hydrophobic central core with their hydrophilic poly( ethylene oxide) chains facing outward. At a given temperature, micellization occurs in dilute compositions in selected solvents above the critical micellar concentration. At higher concentrations, above a critical gel concentration, the micelles can order into a lattice. 1 CA 03155909 2022· 4- 25 [0004) Commonly used types of poloxamers 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. Poloxomer 407 (Pluronic® F- 127) has a good solubilizing capacity, low toxicity and has been used for biomedical applications. [0005) Poloxamer 407 has an 1-Il.,B (hydrophile-lipophile) value of 22. In general, HLB numbers >IO have an affinity for water (hydrophilic) and number <IO have an affinity for oil (lipophilic). Aqueous compositions of Poloxamer 407 show thermoreversible properties, wherein they transform from liquid-like behavior to gel-like behavior above the sol-gel temperature. Above the sol-gel transition temperature the compositions behave more solid-like, whereas below the sol-gel temperature the compositions behave more liquid-like (fluid). The rheological flow behavior ofpoloxamer compositions can be either Newtonian (liquid-like) or nonNewtonian (gel-like) based on the temperature and concentration of polymer. Below the sol-gel transition temperature, poloxamer compositions exhibit Newtonian properties, whereas above the sol-gel transition point they exhibit non-Newtonian properties. [0006) Apart from temperature, gelation is also dependent on the concentration of poloxamer in composition. Gel formation occurs when the concentration of poloxamer is above critical mi cellar concentration. Poloxamer compositions of 20-30 wt. % concentrations form clear liquids at cold temperatures of 4-5 °C, but gel at room temperature (~22-25 °C). The gel can return to liquid by cooling. [0007) concentration. The sol-gel transition temperature decreases with increase in the poloxamer [0008) Excipients may also influence the sol-gel transition temperature of the poloxamers. For example, hydrochloric acid, propylene glycol and ethanol increase the sol-gel transition temperature, whereas sodium chloride, Na2HPO4 and sodium alginate, as well as an increase in pH and ionic strength, decrease the gel-sol transition temperature. The gel systems 2 CA 03155909 2022· 4- 25 have primarily been used in topical biomaterials for the sustained release of active pharmaceutical agents. Sustained release of such drugs helps to maintain therapeutic drug concentrations over a longer period-of-time and helps to decrease dosage intervals, thereby increasing patient compliance. [0009) There has been extensive research into poloxamers, which has resulted in various patent filings incuding, 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 Public