Gels for Transdermal Delivery

• US 20110230816A1
• Filed: 08/31/2010
• Published: 09/22/2011
• Est. Priority Date: 03/18/2010
• Status: Abandoned Application

• Current Assignee: Covidien LP (Medtronic Plc)
• Original Assignee: Tyco Healthcare Group LP (Medtronic Plc)
• Inventors: Copp-Howland, Warren
• Application Number:
  US12/872,539
• Publication Number:
  US 20110230816A1
• Time in Patent Office: Days
• US Class Current: 604/20
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/245 Amino benzoic acid types, e.g. procaine, novocaine salicylic acid esters A61K31/60
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/465 Nicotine; Derivatives thereof
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/60 Salicylic acid; Derivatives thereof
• CPC Class Codes: A61K 31/618 having the carboxyl group in position 1 esterified, e.g. salsalate
• CPC Class Codes: A61K 31/726 Glycosaminoglycans, i.e. mucopolysaccharides chondroitin sulfate, dermatan sulfate A61K31/737
• CPC Class Codes: A61K 36/16 Ginkgophyta, e.g. Ginkgoaceae (Ginkgo family)
• CPC Class Codes: A61K 36/258 Panax (ginseng)
• CPC Class Codes: A61K 36/82 Theaceae (Tea family), e.g. camellia
• CPC Class Codes: A61K 36/87 Vitaceae or Ampelidaceae (Vine or Grape family), e.g. wine grapes, muscadine or peppervine
• CPC Class Codes: A61K 36/886 Aloeaceae (Aloe family), e.g. aloe vera
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation
• CPC Class Codes: A61P 23/02 Local anaesthetics
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system

Abstract

The present disclosure provides hydrogels that are suitable for drug delivery. In embodiments, hydrogels of the present disclosure may be used for transdermal delivery of bioactive agents, including drugs. The hydrogels of the present disclosure may also be useful as conductive compositions for use with electrodes.

Claims

1. A hydrogel composition comprising:

a polymeric component selected from the group consisting of gelatin, polysaccharides, crosslinked acrylamide polymers, hydroxyethylmethacrylate polymers, crosslinked polyhydroxyethylacrylate, polymerized, crosslinked 2-acrylamido-2-methylpropane sulfonic acid polymers, crosslinked polyvinylpyrrolidone, polyacrylic acid, copolymers of the foregoing, one or more salts thereof, and combinations thereof;

at least one penetration enhancer selected from the group consisting of sulfoxides, alcohols, pyrrolidones, laurocapram, solvents, fatty alcohols, amides, amino acids, azones, oils, fatty acids and their esters, macrocycles, phospholipids, glycols, and combinations thereof; and

at least one bioactive agent.

2. The composition of claim 1, wherein the polymeric component comprises a copolymer comprising a first monomer comprising a mixture of acrylic acid and a salt thereof, present in an amount of from about 8 weight % to about 85 weight % of the copolymer, and a second monomer of the formula CH₂═

CHC(O)XR, in which X is O or NH and R is an unsubstituted or substituted alkyl group of from about 1 to about 5 carbon atoms present in an amount of from about 15 weight % to about 92 weight % of the copolymer.

3. The composition of claim 1, wherein the penetration enhancer is selected from the group consisting of dimethylsulfoxide, decylmethyl sulfoxide, tetradecylmethyl sulfoxide, methanol, ethanol, 2-propanol, 2-pyrrolidone, N-methyl-2-pyrrolidone, N-(2-hydroxyethyl)pyrrolidone, acetone, dimethyl acetamide, dimethyl formamide, tetrahydrofurfuryl alcohol, lauryl alcohol, N,N-diethyl-m-toluamide, L-amino acids, menthol, peppermint oil, oleic acids, lauryl acids, isopropyl myristate, glycerol monolaurate, cyclopentadecanone, lecithin, ethoxy diglycol, and combinations thereof, present in an amount of from about 2% to about 50% by weight of the hydrogel.

4. The composition of claim 1, wherein the bioactive agent is selected from the group consisting of cosmeceuticals, drugs, biocidal agents, antimicrobial agents, antibiotics, growth factors, anti-clotting agents, clotting agents, analgesics, anesthetics, pain relievers, anti-inflammatory agents, wound repair agents, hormones, heart medications, nicotine, and combinations thereof.

5. The composition of claim 1, wherein the bioactive agent comprises an analgesic selected from the group consisting of methyl salicylate, salicylic acid, acetaminophen, oxycodone, hydrocodone, COX-2 inhibitors, non-steroidal anti-inflammatory drugs, and combinations thereof.

6. The composition of claim 1, wherein the bioactive agent comprises an anesthetic selected from the group consisting of benzocaine, bupivacaine, butesin picrate, chloroprocaine, ethyl chloride, fluori-methane, lidocaine HCl, mepivacaine, pramoxine HCl, and combinations thereof.

7. The composition of claim 1, wherein the bioactive agent comprises a cosmeceutical selected from the group consisting of ace mannan, aloe powder, aloe vera gel, alpha-hydroxy acids, ammonium glycolate, α

-bisabolol, ascorbic acid, beta-hydroxy acids, calamine, capsaicin, camphor, centella asiatica extract, dipotassium glycyrrhizinate, ginkgo biloba extract, ginseng extract, glucosamine, grape seed extract, green tea extract, horsetail extract, hydroquinone, kinetin, minoxidil, menthol, methyl sulfonyl methane, retinoic acid, vitamin A palmitate, vitamin E acetate, and combinations thereof.

8. The composition of claim 1, wherein the bioactive agent is present in an amount of from about 0.1% by weight of the hydrogel to about 20% by weight of the hydrogel.

9. The composition of claim 1, wherein the hydrogel further comprises a humectant selected from the group consisting of glycerol, sorbitol, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, and combinations thereof.

10. The composition of claim 9, wherein the humectant, optionally in combination with water, is present in an amount of from about 3% to about 80% by weight of the hydrogel.

11. The composition of claim 1, wherein the hydrogel further comprises an electrolyte present in an amount of from about 0.5% by weight to about 10% by weight of the hydrogel, and optionally a neutralizer selected from the group consisting of ammonium hydroxide, sodium hydroxide, potassium hydroxide, lithium hydroxide, and combinations thereof, optionally a cross linking agent selected from the group consisting of N—

N′

-methylene bis-acrylamide, diethylene glycol diacrylate, diethylene glycol dimethacrylate, trimethylolpropane triacrylate, trimethylolpropane trimethacrylate, ethoxylated trimethylolpropane triacrylate, ethoxylated trimethylolpropane trimethacrylate, pentaerythritol triacrylate, pentaerythritol trimethacrylate, pentaerythritol tetraacrylate, pentaerythritol tetramethacrylate, polyethylene glycol diacrylate, polyethylene glycol dimethacrylate, and combinations thereof, and optionally a polymerization initiator selected from the group consisting of 2,2-azobisisobutyronitrile, 1-hydroxycyclohexylphenyl ketone, 2-hydroxy-2-methyl-1-phenylpropan-1-one, 2-hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2-methyl-1-propan-1-one, 3,2-dimethoxy-2-phenyl acetophenone, benzophenone, and combinations thereof.

12. A method comprising:

contacting a tissue of an animal with the hydrogel of claim 1;

allowing the hydrogel of claim 1 to adhere to the tissue; and

releasing the bioactive agent from the hydrogel.

13. A medical electrode comprising:

a substrate;

a conductive composition on at least a portion of a surface of the substrate, the conductive composition comprising at least one hydrogel comprising;

a polymeric component selected from the group consisting of gelatin, polysaccharides, crosslinked acrylamide polymers, hydroxyethylmethacrylate polymers, crosslinked polyhydroxyethylacrylate, polymerized, crosslinked 2-acrylamido-2-methylpropane sulfonic acid polymers, crosslinked polyvinylpyrrolidone, polyacrylic acid, copolymers of the foregoing, one or more salts thereof, and combinations thereof;

at least one penetration enhancer selected from the group consisting of sulfoxides, alcohols, pyrrolidones, laurocapram, solvents, fatty alcohols, amides, amino acids, azones, oils, fatty acids and their esters, macrocycles, phospholipids, glycols, and combinations thereof; and

at least one bioactive agent.

14. The medical electrode of claim 13, wherein the polymeric component comprises a copolymer comprising a first monomer comprising a mixture of acrylic acid and a salt thereof, present in an amount of from about 8 weight % to about 85 weight % of the copolymer, and a second monomer of the formula CH₂═

CHC(O)XR, in which X is O or NH and R is an unsubstituted or substituted alkyl group of from about 1 to about 5 carbon atoms present in an amount of from about 15 weight % to about 92 weight % of the copolymer.

15. The medical electrode of claim 13, wherein the penetration enhancer is selected from the group consisting of dimethylsulfoxide, decylmethyl sulfoxide, tetradecylmethyl sulfoxide, methanol, ethanol, 2-propanol, 2-pyrrolidone, N-methyl-2-pyrrolidone, N-(2-hydroxyethyl)pyrrolidone, acetone, dimethyl acetamide, dimethyl formamide, tetrahydrofurfuryl alcohol, lauryl alcohol, N,N-diethyl-m-toluamide, L-amino acids, menthol, peppermint oil, oleic acids, lauryl acids, isopropyl myristate, glycerol monolaurate, cyclopentadecanone, lecithin, ethoxy diglycol, and combinations thereof, present in an amount of from about 2% to about 50% by weight of the hydrogel.

16. The medical electrode of claim 13, wherein the bioactive agent is selected from the group consisting of cosmeceuticals, drugs, biocidal agents, antimicrobial agents, antibiotics, growth factors, anti-clotting agents, clotting agents, analgesics, anesthetics, pain relievers, anti-inflammatory agents, wound repair agents, hormones, heart medications, nicotine, and combinations thereof.

17. The medical electrode of claim 13, wherein the bioactive agent comprises an analgesic selected from the group consisting of methyl salicylate, salicylic acid, acetaminophen, oxycodone, hydrocodone, COX-2 inhibitors, non-steroidal anti-inflammatory drugs, and combinations thereof.

18. The medical electrode of claim 13, wherein the bioactive agent comprises an anesthetic selected from the group consisting of benzocaine, bupivacaine, butesin picrate, chloroprocaine, ethyl chloride, fluori-methane, lidocaine HCl, mepivacaine, pramoxine HCl, and combinations thereof.

19. The medical electrode of claim 13, wherein the bioactive agent comprises a cosmeceutical selected from the group consisting of ace mannan, aloe powder, aloe vera gel, alpha-hydroxy acids, ammonium glycolate, α

-bisabolol, ascorbic acid, beta-hydroxy acids, calamine, capsaicin, camphor, centella asiatica extract, dipotassium glycyrrhizinate, ginkgo biloba extract, ginseng extract, glucosamine, grape seed extract, green tea extract, horsetail extract, hydroquinone, kinetin, minoxidil, menthol, methyl sulfonyl methane, retinoic acid, vitamin A palmitate, vitamin E acetate, and combinations thereof.

20. The medical electrode of claim 13, wherein the bioactive agent is present in an amount of from about 0.1% by weight of the hydrogel to about 20% by weight of the hydrogel.

21. The medical electrode of claim 13, wherein the hydrogel further comprises a humectant selected from the group consisting of glycerol, sorbitol, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, and combinations thereof.

22. The medical electrode of claim 21, wherein the humectant, optionally in combination with water, is present in an amount of from about 3% to about 80% by weight of the hydrogel.

23. The medical electrode of claim 13, wherein the hydrogel further comprises an electrolyte present in an amount of from about 0.5% by weight to about 10% by weight of the hydrogel, and optionally a neutralizer selected from the group consisting of ammonium hydroxide, sodium hydroxide, potassium hydroxide, lithium hydroxide, and combinations thereof, optionally a cross linking agent selected from the group consisting of N—

N′

-methylene bis-acrylamide, diethylene glycol diacrylate, diethylene glycol dimethacrylate, trimethylolpropane triacrylate, trimethylolpropane trimethacrylate, ethoxylated trimethylolpropane triacrylate, ethoxylated trimethylolpropane trimethacrylate, pentaerythritol triacrylate, pentaerythritol trimethacrylate, pentaerythritol tetraacrylate, pentaerythritol tetramethacrylate, polyethylene glycol diacrylate, polyethylene glycol dimethacrylate, and combinations thereof, and optionally a polymerization initiator selected from the group consisting of 2,2-azobisisobutyronitrile, 1-hydroxycyclohexylphenyl ketone, 2-hydroxy-2-methyl-1-phenylpropan-1-one, 2-hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2-methyl-1-propan-1-one, 2,2-dimethoxy-2-phenylacetophenone, benzophenone, and combinations thereof.

24. A method comprising:

contacting a tissue of an animal with the medical electrode of claim 13;

allowing the hydrogel of claim 13 to adhere to the tissue; and

releasing the bioactive agent from the hydrogel.

25. The method of claim 24, wherein electric current applied to the electrode enhances release of the bioactive agent from the hydrogel.