US20050101543A1 - Treatments for neurogenetic disorders, impulse control disorders, and wound healing - Google Patents

Treatments for neurogenetic disorders, impulse control disorders, and wound healing Download PDF

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US20050101543A1
US20050101543A1 US11/013,259 US1325904A US2005101543A1 US 20050101543 A1 US20050101543 A1 US 20050101543A1 US 1325904 A US1325904 A US 1325904A US 2005101543 A1 US2005101543 A1 US 2005101543A1
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topiramate
composition
disorders
administered
alkyl
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Nathan Shapira
Mary Lessig
Daniel Driscoll
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University of Florida
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Assigned to FLORIDA, UNIVERSITY OF reassignment FLORIDA, UNIVERSITY OF ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: DRISCOLL, DANIEL JOHN, LESSIG, MARY CATHERINE, SHAPIRA, NATHAN ANDREW
Publication of US20050101543A1 publication Critical patent/US20050101543A1/en
Assigned to LESSIG, MARY CATHERINE, SHAPIRA, NATHAN ANDREW, DRISCOLL, DANIEL JOHN reassignment LESSIG, MARY CATHERINE ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: UNIVERSITY OF FLORIDA
Assigned to SHAPIRA, NATHAN ANDREW reassignment SHAPIRA, NATHAN ANDREW ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: LESSIG, MARY CATHERINE, DRISCOLL, DANIEL JOHN
Priority to US11/830,906 priority patent/US8084491B2/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/18—Sulfonamides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/255—Esters, e.g. nitroglycerine, selenocyanates of sulfoxy acids or sulfur analogues thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7024—Esters of saccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system

Definitions

  • Hereditary ataxias and related disorders such as Friedreich ataxia, ataxia telangiectasia, olivopontine cerebellar degeneration, Ramsay Hunt syndrome, abetalipoproteinemia, Machado-Joseph disease, and familial spastic paraparesis;
  • Movement disorders such as Juvenile Huntington disease, the dystonias including blepharospasm and spasmodic torticolis, tremor, myoclonus, and Hallervorden-Spatz disease;
  • Phakomatoses, or neurocutaneous syndromes such as neurofibromatosis, tuberous sclerosis, Sturge-Weber, and Von Hippel-Landau disease;
  • Mitochondrial encephalomyopathies such as the MELAS syndrome, Keams-Sayre, and Leigh disease
  • Hereditary disorders of nerve and muscle such as infantile spinal muscular atrophy, Charcot-Marie-Tooth disease, hereditary sensory and auto
  • disorders of defective cellular migration such as lissencephaly, heterotopias
  • neural tube defects such as congenital hydrocephalus, myoclonic epilepsy, attention deficit hyperactivity disorder (ADHD), and narcolepsy.
  • ADHD attention deficit hyperactivity disorder
  • ADHD affects about 4% to 6% of the U.S. population. ADHD is not limited to children and is a chronic lifetime disease. Approximately one-half to two-thirds of children with ADHD will continue to have significant problems in adulthood and experience difficulties which impact employment, familial, and social relationships.
  • some common symptoms of ADHD include: (1) often fails to give close attention to details or makes careless mistakes; (2) often has difficulty sustaining attention to tasks; (3) often does not seem to listen when spoken to directly; (4) often fails to follow instructions carefully and completely; (5) losing or forgetting important things; (6) feeling restless, often fidgeting with hands or feet, or squirming; (7) running or climbing excessively; (8) often talks excessively; (9) often blurts out answers before hearing the whole question; and (10) often has difficulty awaiting turn. It should be kept in mind that the exact nature and severity of ADHD symptoms varies from person to person however. Approximately one-third of people with ADHD do not have the hyperactive or overactive behavior component.
  • these behaviors must be excessive, long-term, and pervasive.
  • the behaviors must appear before age 7, and continue for at least 6 months.
  • a crucial element requires that the behaviors must create a real handicap in at least two areas of a person's life, such as school, home, work, or social settings.
  • Carbamazepine (Tegretol) has been reported to be useful for the treatment of patients experiencing sudden confusion and depression. Within weeks of initiating treatment, the patients experienced fewer incidences of sudden confusion and depression, and an increase in attention and focus. Persinger, M. A., “Subjective improvement following treatment with carbamazepine (Tegretol) for a subpopulation of patients with traumatic brain injuries”, Percept Mot Skills 90:37-40 (2000). Carbamazepine has also been shown to be effective in treating children with features of ADHD. Silva, R. R.; Munoz, D.
  • gabapentin is an equally effective add-on medication.
  • PWS Prader-Willi Syndrome
  • PWS is a neurogenetic multisystem disorder characterized by infantile hypotonia, mental retardation, short stature, hypogonadism, dysmorphic features, and hyperphagia with a high risk of obesity.
  • behavioral and psychiatric manifestations include self-injury (e.g. gouging, nail biting, and skin picking), explosive outbursts, oppositional behavior, obsessive ruminations, and compulsive behaviors including hoarding, counting, and arranging.
  • PWS is typically a sporadic condition, which usually results from a deletion in chromosome 15q11-q13 or maternal uniparental disomy of chromosome 15. Glenn, C.
  • PWS is also a relatively common genetic condition with an estimated prevalence of approximately 1/10,000 to 1/25,000.
  • Driscoll, D. J.; Thomas, P. Y.; Nicholls, R. D. “Genomic imprinting: potential function and mechanisms revealed by the Prader-Willi and Angelman syndromes”, Mol Hum Reprod 3:321-332 (1997).
  • PSP Pathological skin picking
  • PSP is often considered an obsessive compulsive spectrum disorder (Goldsmith, T. D.; Shapira, N. A.; Phillips, K. A.; et al., “Obsessive Compulsive Spectrum Disorders”; in: Swinson, R. P.; Antony, M. M.; Rachman, S.; Richter, M. A.
  • the subject invention has, surprisingly, found improvements in impulsivity control, without negative effects on attention and concentration, in patients treated with topiramate. These observations are unexpected and novel.
  • the subject invention provides methods and compositions for the treatment of neurogenetic disorders, particularly DSM-IV impulse control disorders such as intermittent explosive disorder, kleptomania, pyromania, pathologic gambling, trichotillomania, and other impulse control disorders such as compulsive buying and problematic Internet use.
  • the subject invention provides methods for treating or controlling symptoms associated with ADHD or PWS comprising the administration of therapeutically effective amounts of compositions containing compounds of the formulas I-V.
  • the subject invention provides for methods of promoting wound healing comprising the administration of a therapeutically effective amount of a composition comprising the compounds of formulas I-V.
  • compositions are administered to a wound site via a salve, ointment, or as a component of a bandage or bioadhesive applied to the site of injury.
  • the invention also provides therapeutically effective compositions comprising one or more of the compounds of formulas I-V.
  • FIGS. 1, 3 , 5 , and 7 depict the efficiency ratios of patients treated with topiramate as measured by the Delay Task of the Gordon Diagnostic.
  • FIGS. 2, 4 , 6 , and 8 depict the total correct responses of patients treated with topiramate as measured by the Vigilance Task of the Gordon Diagnostic.
  • FIGS. 9 A-D and 10 A-C depict the progression of wound healing in patients treated with topiramate.
  • FIGS. 11 A-B Photographs of improvement in wound healing for Ms. A on topiramate (75 mg/day) at week 4 ( FIG. 11A ) and 150 mg/day topiramate at week 8 ( FIG. 11B ).
  • FIGS. 12 A-B Photographs of improvement for Mr. B. Mr. B. on 25 mg/day topiramate ( FIG. 12A ), Week 1; Mr. B. on 200 mg/day topiramate ( FIG. 12B ), Week 8.
  • FIGS. 13 A-B Photographs of primary SIB lesions. Ms. C. (right breast), baseline ( FIG. 13A ); Ms. C. on 175 mg/day (right breast), Week 8 ( FIG. 13B ).
  • FIG. 14 Number of ulcerated SIB lesions for Ms. C. as documented by group home staff utilizing systematic full body surveys (* denotes lesions smaller than previous lesions and appearing to result after insect bites).
  • FIGS. 15 A-B Photographic record of Ms. A hair loss at start of treatment ( FIG. 15A ) and during treatment ( FIG. 15B ).
  • FIG. 16 illustrates the reported reduction in the urge of Ms. A to pull hair.
  • FIG. 17 represents the improvement in impulse control for Ms. A during treatment using the Gordon Diagnostic System.
  • FIG. 18 illustrates that Ms. A suffered no significant change in cognitive ability during treatment.
  • the subject invention provides methods and compositions for the treatment of neurogenetic disorders, particularly DSM-IV impulse control disorders such as intermittent explosive disorder, kleptomania, pyromania, pathologic gambling, trichotillomania, and other impulse control disorders such as compulsive buying and problematic Internet use.
  • an individual is treated in methods comprising the administration of therapeutically effective amounts of compositions comprising compounds selected from the group consisting of formulas I-V.
  • therapeutically effective amounts of topiramate are administered to individuals topically or orally.
  • compositions comprising one or more of the compounds disclosed in formulas I-V are administered for the control or treatment neurogenetic disorders.
  • the neurogenetic disorders include PWS and ADHD.
  • the subject invention provides methods and compositions for the treatment or control of ADHD or PWS.
  • the subject invention provides methods for controlling symptoms associated with ADHD or PWS comprising the administration of therapeutically effective amounts of compositions containing compounds of the formulas I-V.
  • One embodiment of the invention provides therapeutically effective compositions comprising one or more of the compounds of formulas I-V and acceptable carriers.
  • the subject invention provides methods of promoting wound healing comprising the administration of a therapeutically effective amount of a composition comprising the compounds of formulas I-V to an individual having a wound.
  • compositions are topically administered to a wound.
  • the compositions may take the form of a salve, ointment, or aerosol applied to the site of injury.
  • the compositions may be administered to the wound site as a component of a bandage or transdermal patch. In these instances, the compositions may be an integral component of the bandage or transdermal patch and are thereby applied to the wound site.
  • therapeutically effective amounts of the compounds comprising formulas I-V are incorporated into bioadhesive compositions useful in wound closure.
  • therapeutically effective amounts compositions comprising the compounds of formulas I-V are administered orally.
  • the subject invention provides methods of promoting wound healing or controlling impulsive behavior in an individual
  • the subject invention provides methods having both human and veterinary utility.
  • the term “individual” includes animals of avian, mammalian, or reptilian origin. Mammalian species which benefit from the disclosed methods include, and are not limited to, apes, chimpanzees, orangutans, humans, monkeys; domesticated animals (pets) such as dogs, cats, guinea pigs, hamsters, Vietnamese pot-bellied pigs, rabbits, and ferrets; domesticated farm animals such as cows, buffalo, bison, horses, donkey, swine, sheep, and goats; exotic animals typically found in zoos, such as bear, lions, tigers, panthers, elephants, hippopotamus, rhinoceros, giraffes, antelopes, sloth, gazelles, zebras, wildebeests, prairie dogs, koala bear
  • Reptiles include, and are not limited to, alligators, crocodiles, turtles, tortoises, snakes, iguanas, and/or other lizards.
  • Avian species include, and are not limited to, chickens, turkeys, pigeons, quail, parrots, macaws, dove, Guinea hens, lovebirds, parakeets, flamingos, eagles, hawks, falcons, condor, ostriches, peacocks, ducks, and swans. Therefore, the subject invention provides methods of controlling the impulse of an individual to scratch, pick, lick, or otherwise cause self-injury by repeated mechanical irritation of an injured area.
  • Bioadhesives incorporating materials to promote wound healing are well known in the art (see, for example, U.S. Pat. Nos. 5,981,606; 5,874,479; 5,863,938; 5,856,364; 5,692,302; 5,674,912; 5,663,208; 5,658,957; 5,658,956; 5,652,274; 5,648,380; 5,646,190; 5,641,814; 5,633,285; 5,631,019; 5,614,561; 5,602,183; 5,578,310, each of which is incorporated by reference in its entirety).
  • Compounds of formulas I-V are anti-epileptic compounds, which are highly effective anti-convulsants.
  • the compounds useful in the practice of the instant invention include the individual isomers, analogs, and homologs of the disclosed anti-convulsant compounds. Racemic mixtures, as well as the isolated enantiomeric forms, of the compounds can also be used in the practice of the subject invention.
  • the compounds useful for the practice of the subject invention include pharmaceutically acceptable salts, for example; alkali metal salts, such as sodium or potassium, ammonium salts, dialkyammonium salts, trialkylammonium salts, tetraalkylammonium salts, and tromethamine salts. Hydrates and other solvates of the compounds are also included within the scope of the compounds useful in the practice of this invention.
  • X 1 is CH 2 or oxygen
  • R 1 is hydrogen or alkyl
  • R 2 , R 3 , R 4 , and R 5 are independently hydrogen or lower alkyl and, when X 1 is CH 2 , R 4 , and R 5 may be alkene groups joined to form a benzene ring and, when X 1 is oxygen, R 2 and R 3 and/or R 4 and R 5 together may be a methylenedioxy group of the following formula: wherein R 6 and R 7 are the same or different and are hydrogen, lower alkyl or are alkyl and are joined to form a cyclopentyl or cyclohexyl ring.
  • R 1 may be hydrogen or an alkyl of about 1 to 4 carbons, such as methyl, ethyl, and isopropyl.
  • Alkyl includes straight and branched chain alkyl.
  • Alkyl groups for R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are of about 1 to 3 carbons and include methyl, ethyl, isopropyl and N-propyl.
  • R 4 and R 5 may combine to form a benzene ring fused to the 6-membered X 1 -containing ring, i.e., R 4 and R 5 are defined by the alkatrienyl group ⁇ CH—CH ⁇ CH—CH ⁇ .
  • X 1 is oxygen and both R 2 and R 3 and R 4 and R 5 together are methylenedioxy groups of the formula wherein R 6 and R 7 are both hydrogen, both alkyl or combine to form a spiro cyclopentyl or cyclohexyl ring, in particularly where R 6 and R 7 are both alkyl such as methyl.
  • X 1 is CH 2 and R 4 and R 5 are joined to form a benzene ring.
  • Another embodiment provides compounds of formula (I) wherein both R 2 and R 3 are hydrogen.
  • R 6 and R 7 may be the same or different and are selected from any of hydrogen or C 1 to C 4 alkyl. In one embodiment, R 6 and R 7 are each hydrogen.
  • R 8 and R 9 may be the same or different and are selected from any of hydrogen or C 1 to C 4 alkyl. In one embodiment, R 8 and R 9 are each C 1 to C 4 alkyl.
  • R 10 and R 11 may be the same or different and are selected from any of azido, halogen, hydroxyl, sulfamoyl (H 2 NSO 2 O), C 1 to C 4 alkoxy, C 1 to C 4 alkyl thiocarbonate (RSC(O)O), C 1 to C 4 alkyl carbonate (ROC(O)O), or C 1 to C 4 alkyl carboxylate (RC(O)O), wherein R is C 1 to C 4 alkyl.
  • R 10 and R 11 are selected from any of C 1 -C 4 alkyl thiocarbonate, halogen or hydroxyl.
  • alkyl and alkoxy include straight and branched chains.
  • alkyl radicals include methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, and t-butyl.
  • Halogen includes bromine, chlorine, fluoride and iodine.
  • Preferred compounds of the formula (II) are those wherein the pyran ring is in the L-sorbopyranose absolute configuration.
  • Particularly preferred compounds of formula (II) are those wherein the pyran ring is in the L-sorbopyranose absolute configuration, R 6 and R 7 are each hydrogen, R 8 and R 9 are each methyl; R 10 is methyl thiocarbonate (CH 3 SC(O)O) and R 11 is halogen; or R 10 and R 11 are both halogen; or R 10 is hydroxyl and R 11 is halogen.
  • Particularly preferred halogens include bromine, chlorine, and iodine.
  • compounds of formula (II) are: (1) 5-deoxy-5-iodo-2,3-O-(1-methylethylidene) -4-[methylthiocarbonyl)]- ⁇ -L-sorbopyranose sulfamate, (i.e., where the compound is in the L-sorbopyranose absolute configuration, R 6 and R 7 are hydrogen, R 8 and R 9 are methyl, R 10 is CH 3 SC(O)O, and R 11 is iodine); (2) 4,5-dibromo-4,5-dideoxy-2,3-O-(1-methylethylidene) - ⁇ -L-sorbopyranose sulfamate, (i.e., where the compound is in the L-sorbopyranose absolute configuration, R 6 and R 7 are hydrogen, R 8 and R 9 are methyl, R 10 and R 11 are bromine); and (3) 5-chloro-5-deoxy-2,3-O-(1-methylethylidene)- ⁇
  • R 12 and R 13 are the same or different and are selected from any of hydrogen, alkyl (C 1 to C 6 ), cycloalkyl (C 3 -C 7 ), allyl, or benzyl. In one embodiment, R 12 and R 13 are each hydrogen. R 14 and R 15 are the same or different and selected from hydrogen or lower alkyl.
  • X 2 may be chosen from carbon (C) or sulfur (S), with the stipulation that when X 2 is carbon, R 16 and R 17 are the same or different and are selected from hydrogen or lower alkyl, whereas when X 2 is sulfur one of R 16 and R 17 is oxygen and the other is a lone pair of electrons or both R 16 and R 17 are oxygen.
  • alkyl includes straight and branched chains.
  • alkyl radicals include methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, and t-butyl.
  • Particularly preferred compounds of formula III are: (1) (1R,2R,3S,4S)-(1,2:3,4-di-O-methylethylidenecyclohexan -1,2,3,4-tetraol-r-yl)methyl sulfamate, (i.e., where R 12 and R 13 are hydrogen, R 14 , R 15 , R 16 , and R 17 are methyl and X 2 is carbon); (2) (1R,2S,3S,4S)-(3,4-O-methylethylidene -1,2-O-sulfonyl-cyclohexan-1,2,3,4-tetraol-4-yl) methyl sulfamate, (i.e., where R 12 and R 13 are hydrogen, R 14 and R 15 are methyl, R 16 is oxygen and R 17 is an electron pair and X 2 is sulfur); and (3) (1R,2S,3S,4S)-(3,4-O-methylethylidene-1
  • Another compound useful in the subject invention is
  • Y is selected from the group consisting of halogens such as F, Cl, Br and I, or trifluoromethyl and alkyl groups containing 1 to 3 carbon atoms when Y alone is attached to the benzene ring; when X 3 , which may be S or O, is present, Y is selected from the group consisting of trifluoromethyl and alkyl groups containing 1 to 3 carbon atoms.
  • R 18 , R 19 , R 20 , and R 21 may be identical or different and are selected from the group consisting of hydrogen, linear or branched alkyl groups containing 1 to 16 carbon atoms, cyclic alkyl groups containing 3 to 16 carbon atoms and aryl groups containing 6 to 8 carbon atoms, and NR 18 R 19 and NR 20 R 21 , identical or different, each may form a 3 to 7-membered aliphatic cyclic compound together with another nitrogen atom or oxygen atom.
  • compositions useful in the practice of this invention comprise one or more of the compounds of formulas I-V admixed with a pharmaceutical carrier.
  • a pharmaceutical carrier may take a wide variety of forms depending on the form of preparation desired for administration, e.g., injection, oral, suppository, topical, or parenteral.
  • any of the usual pharmaceutical media may be employed.
  • suitable carriers and additives include water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents and the like;
  • suitable carriers and additives include starches, sugars, diluents, granulating agents, lubricants, binders, disintegrating agents and the like.
  • tablets and capsules represent the most advantageous oral dosage unit form, in which case solid pharmaceutical carriers are employed.
  • tablets may be sugar coated or enteric coated by standard techniques.
  • Suppositories may be prepared, in which case cocoa butter could be used as the carrier.
  • the carrier will usually comprise sterile water, though other ingredients, for example, for purposes such as aiding solubility or for preservation, may be included.
  • injectable suspensions may also be prepared in which case appropriate liquid carriers, suspending agents and the like may be employed.
  • compositions useful in the practice of the subject invention include salves, cosmetics, ointments, and the like. Such compositions may be topically applied to a site or incorporated into articles of manufacture including, but not limited to, bandages, adhesive strips for the covering of wounds (e.g., BANDAID brand adhesive strips), or transdermal patches. Carriers such as cocoa butter, viscous polyethylene glycols, hydrogenated oils, and such mixtures can be emulsified if desired.
  • Compounds of the subject invention may also be incorporated into cosmetics. Additional materials and substances suitable as carriers for the compounds of formulas I-V are described in the International Cosmetic Ingredient Dictionary and Handbook, 8 th Edition (The Cosmetic, Toiletry, and Fragrance Association (CTFA), 2000), hereby incorporated by reference in its entirety.
  • CTFA Cosmetic, Toiletry, and Fragrance Association
  • the active ingredients can be packaged in pressurized aerosol containers with a propellant, e.g., carbon dioxide, nitrogen, propane, etc. with the usual adjuvants such as cosolvents, wetting agents, etc.
  • a propellant e.g., carbon dioxide, nitrogen, propane, etc.
  • adjuvants such as cosolvents, wetting agents, etc.
  • compositions comprise, as an inactive ingredient, an effective amount of one or more non-toxic, pharmaceutically acceptable ingredient(s).
  • ingredients for use in the compositions include ethanol, dimethyl sulfoxide, glycerol, silica, alumina, starch, calcium carbonate, talc, flour, and equivalent non-toxic carriers and diluents.
  • compositions herein will contain, per dosage unit, e.g., tablet, capsule, powder injection, teaspoonful, suppository, bandage, and the like, from about 0.1 to about 400 mg of the active ingredient.
  • the compositions comprise about 10 mg to 200 mg per dosage unit.
  • the compositions contain comprise about 20 mg to about 100 mg of active ingredient.
  • the compositions comprise about 25 mg of active ingredient per unit dose.
  • Topiramate is currently available for oral administration in round tablets containing 25 mg, 100 mg or 200 mg of active agent.
  • the tablets contain the following inactive ingredients: lactose hydrous, pregelatinized starch, microcrystalline cellulose, sodium starch glycolate, magnesium stearate, purified water, carnauba wax, hydroxypropyl methyl cellulose, titanium dioxide, polyethylene glycol, synthetic iron oxide, and polysorbate 80.
  • the Delay Task requires that the subject inhibit responding (pressing a button and then refraining from pressing the button again for at least 6 seconds) in order to earn points.
  • the Delay Task measures the subject's ability to suppress and delay impulsive behavioral responses. While focusing and sustaining attention usually facilitate Delay Task performance, the Delay Task maximally draws on a subject's ability to inhibit impulsive responses.
  • the Delay Task's total efficiency ratio (EF) is considered the best indicator (score ranges from 0 to 1) of the level of impulsivity with the lower the score (such as less than 0.5) indicating higher impulsivity and poor self-control.
  • the Vigilance Task measures the subject's ability to focus attention on a task and to maintain this attention over a period of time without reinforcement.
  • the correct responses (CR) of the Vigilance Task measures the level of alertness and is a measure of the subjects attentional processes.
  • JAS-002 (patient Number 2) had a baseline total efficiency ratio (ER) of 0.02, approximately 8 standard deviations below the normal range and well below the first percentile in regards to the Delay task. This falls markedly within the range of an “abnormal” performance as stated in the rating score manual provided by the manufacturer of the GDS.
  • ER total efficiency ratio
  • JAS-002 demonstrated dramatic improvement in ER (a value of 0.98), well within the normal range of performance.
  • JAS-002 continued with improvements in ER (a value of 0.85), within the normal range of performance. Attention as evaluated by the Vigilance Task for JAS-002 showed essentially no change for CR from 39 at baseline to 38 (at a dose of 175 mg/day) at 2 months.
  • MJG-001 For patient Number 1 (MJG-001), a significant improvement has been noted.
  • MJG-001's ER for the Delay Task was at a value of 0.06 (approximately 7 standard deviations below the average ER) demonstrating a severe impairment of impulsivity.
  • MJG-001 showed moderate improvement with a Delay Task ER of 0.24.
  • visit 5 approximately 1.5 months after starting medication (at a dose of 75 mg/day), MJG-001 demonstrated a substantial improvement with an ER value of 0.46 and two weeks later (at a dose of 125 mg/day) had an ER value of 0.70.
  • MJG-001 demonstrated a substantial improvement with an ER value of 0.50.
  • the Vigilance Task for MJG-001 showed some variability up and down during the study and, after approximately 2 months, showed a mild decrease of CR from 43 to 41 (at a dose of 150 mg/day).
  • Patient Number 3 (GFV-003) has also shown a severe deficit in impulsivity and focusing; baseline ER was 0.02 (a value 8 standard deviations below the normal range).
  • baseline ER was 0.02 (a value 8 standard deviations below the normal range).
  • GFV-003 had improved to an 0.09 ER and by week 4 (at a dose of 100 mg/day) to an ER of 0.19, and by 2 months (at a dose of 200 mg/day) the ER was at 0.10.
  • the Vigilance Task for GFV-003 showed variability on topiramate and by the end of two months was essentially unchanged with a CR decreasing from 16 at baseline to 15 at 2 months.
  • Patient #4 also showed abnormal performance on the Delay task (ER of 0.35).
  • MCK-004 had improved to an ER of 0.51, by the 2 nd week on 50 mg/day topiramate, the ER was 0.76, and continued improvement by the 3 rd week on 75 mg/day with an ER of 0.65 and by two months at a dose of 150 mg/day, her ER continued to be improved at 0.64.
  • the Vigilance Task for MCK-004 shows mild decrease from baseline CR of 38 to 34 (by the 8 th week on 150 mg/day).
  • topiramate for impulsivity, without negative effects on attention and concentration, is both novel and clinically applicable.
  • Disorders with impulsivity and deficits in attention and concentration are difficult to manage for both the patient and their caregiver, especially in cases of dementia.
  • Impulsivity and lack of concentration can severely handicap day-to-day functioning in all age groups affected by these disorders.
  • Patient #3 also has pathologic skin picking (PSP) in addition to food seeking behavior.
  • PSP pathologic skin picking
  • Patient #3 has a chronic large lesion on his lower left arm.
  • topiramate 25 mg/day
  • the 4 th week on topiramate at 100 mg/day
  • the lesion on his lower left arm had completely healed over.
  • the progression of wound healing is provided in FIGS. 9 A-D and 12 A-B.
  • Patient #1 has pathologic skin picking (PSP) in addition to food seeking behavior.
  • PSP pathologic skin picking
  • several large lesions (where she skin picks) on her right arm, legs, and lips were clearing up quickly (within 5 days) after topiramate was initiated at 25 mg/day.
  • the patient has continued to do well in terms of skin clearing.
  • a large lesion on her right arm completely healed over after about 2 months on topiramate (at a dose of 125 mg/day).
  • the progression of wound healing is provided in FIGS. 10 A-C and 11 A-B.
  • topiramate for PSP and related disorders is also novel and clinically applicable.
  • pathologic skin picking also referred to as neurotic excoriation, repetitive skin picking, compulsive skin picking, and dermatotillomania
  • obsessive-compulsive spectrum disorders i.e., repetitive self-mutilation (RSM), oncophagia, rhinotillxomania, trichotillomania
  • RSM repetitive self-mutilation
  • Screening measures included a physical examination, psychiatric background, medication history, blood draw for laboratory assessment (CBC, SMA-12, urinalysis, and a B-hCG for women of childbearing potential), and the Structured Clinical Interview for DSM-IV, Patient Edition (SCID-P). Weekly assessments of weight loss, participant functioning, and safety measures including blood pressure and pulse were taken by the investigators at each visit. Participants are residents of group homes operated by the Association of Retarded citizens, Alachua County, Florida (ARC). These homes are monitored, thereby allowing recording of participants' behavioral and psychiatric manifestations as well as their medication management. Participants began pharmacotherapy with topiramate at 25 mg of drug given in the evening for 7 days. After 14 days, their daily dose could be increased in increments of up to 50 mg/week for the next 6 weeks.
  • Case 1 Ms. A. is a 19 year-old female who through DNA methylation testing was positive for PWS and shown to have a chromosomal deletion through FISH and DNA polymorphism analyses. Ms. A. has a history of hoarding and severe skin picking dating to childhood. Current concomitant psychiatric medications include fluoxetine 60 mg/day and naltrexone 50 mg/day. Psychiatric intervention dated back to 1992 when the subject began therapy with clomipramine and fenfluramine, both of which were unsuccessful in managing her behavior and weight problem.
  • Mr. B. is a 29 year-old male confirmed to be a chromosomal deletion as described above. He has a history of severe food seeking and skin picking dating to childhood. Mr. B does not have a history of taking psychotropic medications and had declined a previous recommendation to take fluoxetine. Initial healing of his primary lesion (a round 1.5 cm diameter ulcerated lesion) was noted within one week of initiating topiramate treatment (25 mg/day) at which point photographic records were started. Mr. B also experienced some increased irritability when topiramate was initiated. Irritability returned towards baseline by Week 8. Mr. B also experienced a decrease in his weight from 180.0 lbs at baseline to 176.8 lbs at Week 8. By Week 8 of topiramate (200 mg/day), Mr. B. had experienced remission of his self-injurious behavior (SIB) with resultant healing and complete collagenation of his primary lesion (FIGS. 9 A-D and 12 A-B).
  • SIB self-injurious behavior
  • Ms. C. is a 32 year-old female confirmed to be a chromosomal deletion.
  • Concomitant psychotropic medications include fluoxetine 20 mg/day. She has a history of food seeking and skin picking dating to childhood. Due to her employment, Ms. C. picks in multiple concealed locations (e.g., her chest, breasts, and the top of her legs). Because of her secrecy regarding SIB, the staff members of her group home daily perform full body surveys. As a result of previous experience with Ms. A and Mr. B, photographic records of her lesions were started prior to initiation of topiramate ( FIG. 13 ).
  • Topiramate is able to attenuate self-injurious behavior in a patient population where SIB is common and difficult to manage and treat. All three subjects have longstanding histories of self-injury, and two subjects (Ms. A. and C.) had failed previous psychotropic medication interventions. Furthermore, all three PWS subjects have chosen to continue on topiramate after the 8-week trial (8 months for Ms. A., 7 months for Mr. B., and 4 months for Ms. C.) with continued improvement in self-injury. Improvement in self-injury was noted by both investigators and in systematic body evaluations by the group home in one subject (Ms. C.). Additionally, while individuals with PWS often pick surreptitiously and pick even when they describe having no urges, all three subjects reported decreased urges to pick while on topiramate.
  • Canine acral lick dermatitis also known as lick granuloma, acral pruritic nodule, and neurodermatitis
  • ALD acral lick dermatitis
  • lick granuloma acral pruritic nodule
  • neurodermatitis is a common self-inflicted skin disorder in dogs in which localized alopecia and epidermal hyperplasia and fibrosis are caused by continued licking, biting, and/or scratching one or more areas usually near the carpus or hock.
  • the licking of the paws or flank causes significant local trauma and, in extreme cases, may require surgery and steroids. Occasionally, the animal must be put to death because of chronic ulceration or osteomyelitis.
  • ALD etiology of ALD
  • ALD etiology of ALD
  • Certain large breeds appear to be more susceptible, such as German Shepherds, Labrador Retrievers, and Great Danes.
  • the repetitive self-licking, chewing, or scratching creates areas of hair loss and the production of lesions which may range in size from several centimeters to the entire surface of the limb. This stereotypic behavior prevents the lesions from healing and may cause discomfort, pain and, in severe cases, may prove crippling.
  • a double-blind placebo-controlled trial of 8 weeks duration (6 week treatment and 2 week taper) will be conducted.
  • One-half of the dogs receive placebo.
  • the dogs will start at 2 mg/kg in a split dose (1 mg/kg twice a day) for the first two weeks.
  • the dose will be increased 2 mg/kg a week as tolerated for the next four weeks.
  • the maximum dosage will not exceed 10 mg/kg.
  • This dosage strategy is based upon the target dose for seizures, which is 5 to 10 mg/kg in split doses.
  • Topiramate or placebo will be administered via gelatin capsules once daily (5 minutes before feeding). Owners will be instructed to avoid feeding dogs anything in addition to their regular diet. In addition to adhering to the dogs' routine (e.g., food, exercise, and training), owners will also be asked to maintain environmental conditions for the duration of the study.
  • a video camera will record the dogs' behavior for 1 hour each week for the 6 weeks of the trial.
  • the primary behavior of interest is self-licking or self-chewing of the granulomatous lesion.
  • the measure of time the dogs are involved in licking or chewing will be computerized.
  • the evaluator will press the designated key when the dog's tongue or lips first makes contact with the lesion, and at the end of a continuous bout of licking or chewing when the dog lifts its head from the lesion and transfers its attention elsewhere.
  • a 2-week taper period will follow the 6-week treatment period.
  • study medication will be reduced by approximately 25% for 3 days.
  • the dosage will be reduced by another 25%.
  • the remaining dose will be reduced in half again and on day 13 all study medication will be stopped.
  • the dogs' last visit will be day 14 of the taper period.
  • Topiramate was used as an adjunct therapy in a 38 year-old female with a 9-year history of trichotillomania. She was on a stable dose combination of fluvoxamine and clomipramine. While the fluvoxamine/clomipramine combination was therapeutic for 3 years, 6 months ago Ms. A experienced an increase in hair pulling predominately on the left side of her head. The investigators have made photographic records of Ms. A's hair loss (FIGS. 15 A-B) and she has been evaluated psychometrically for impulse control. Ms. A was started on a 25 mg dose of topiramate at night and was gradually titrated in increments of 25 mg to 150 mg at night. Preliminary results suggest the addition of topiramate to this combination therapy effective for trichotillomania.
  • Ms Ms.
  • A reported a lessening of the urges to pull her hair starting at a relatively low dose (approximately 50 mg/ day).
  • Ms. A reported a significant reduction in the urge to pull by 3 weeks following the addition of topiramate and this improvement has been maintained for 14 weeks ( FIG. 16 ). Although patient described decreased urges to pull hair, her re-growth was minimal.
  • topiramate augmentation After initial success with topiramate augmentation, the patient is currently being weaned off clomipramine and is currently on 25 mg/day from 100 mg/day without any increase in urges to hair pull. Ms. A has experienced weight loss of approximately 5 lbs which she reports as a positive side effect. Possible other side effects of topiramate administration include disruption of attention and concentration and cognitive deficits such as word finding difficulties.
  • the patient has continued to see a reduction in the urge to, as well as in the time, spent, pull her hair. Re-growth of hair at the sites previously pulled has also been observed.
  • the patient is currently on 475 mg topiramate (p.o. q.h.s.).
  • a 19-year-old female with a history of trichotillomania and skin picking has also been treated in accordance with the invention. She presented with skin lesions on her hands and face that resulted from picking at pimples (face) and pulling of hair on the backs of her hands.
  • Several medications, in various classes, were previously tried without improvement (including mirtazapine, citalopram, gabapentin, paroxetine, nefazadone, and sertaline).
  • the initiation of topiramate has resulted in the resolution of her trichotillomania, with noticeable re-growth of hair on the backs of her hands at 200 mg. p.o. q.h.s.) and has also resulted in improvements in the facial skin lesions. She is currently on 300 mg q.d. topiramate monotherapy.
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Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002043731A2 (en) * 2000-11-30 2002-06-06 University Of Florida Treatments for neurogenetic disorders, impulse control disorders, and wound healing
US6462084B1 (en) * 2001-05-14 2002-10-08 Brookhaven Science Associates, Llc Treatment for obsessive-compulsive disorder (OCD) and OCD-related disorders using GVG
AU2003239455A1 (en) * 2002-05-14 2003-12-02 Ralph Ryback Method for treating dermatoses and tissue damage
WO2004050081A1 (en) * 2002-12-02 2004-06-17 University Of Florida Treatments for benign tumors, cancers, neoplasias, and/or other inflammatory disorders or diseases
WO2008027557A2 (en) 2006-08-31 2008-03-06 Spherics, Inc. Topiramate compositions and methods of enhancing its bioavailability
CA2618240C (en) 2006-11-17 2015-01-20 Supernus Pharmaceuticals, Inc. Sustained-release formulations of topiramate
CN102218044A (zh) * 2006-12-04 2011-10-19 苏佩努斯制药公司 托吡酯的增强的立即释放制剂
EP2306899B1 (en) 2008-06-12 2014-08-13 Amygdala Pty Ltd Detection of hypokinetic and/or hyperkinetic states
KR20110074611A (ko) * 2008-10-21 2011-06-30 노보더믹스 인터내셔널 리미티드 상피 조직의 치료 조성물
KR20120092175A (ko) 2009-12-04 2012-08-20 죤 이. 그랜트 카테콜-0-메틸-트랜스퍼라제 저해제를 사용한 충동 제어 장애의 치료
TWI570472B (zh) * 2011-10-03 2017-02-11 三菱瓦斯化學股份有限公司 芳香族聚碳酸酯製偏光透鏡
TWI474831B (zh) 2012-09-14 2015-03-01 Univ Taipei Medical 免疫調節蛋白於促進傷口癒合或組織損傷治療的用途
WO2014131090A1 (en) * 2013-03-01 2014-09-04 Global Kinetics Corporation Pty Ltd System and method for assessing impulse control disorder
US10736577B2 (en) 2014-03-03 2020-08-11 Global Kinetics Pty Ltd Method and system for assessing motion symptoms
WO2017015049A1 (en) * 2015-07-17 2017-01-26 Ovid Therapeutics Inc. Methods of treating developmental disorders with gaboxadol
CA3184332A1 (en) * 2020-06-26 2021-12-30 Artur Manuel Cavaco Paulo Composition for hair follicle modulation, methods and uses thereof

Citations (78)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4513006A (en) * 1983-09-26 1985-04-23 Mcneil Lab., Inc. Anticonvulsant sulfamate derivatives
US5384327A (en) * 1992-12-22 1995-01-24 Mcneilab, Inc. Anticonvulsant sorbopyranose sulfamates
US5498629A (en) * 1993-12-23 1996-03-12 Ortho Pharmaceutical Corporation Anticonvulsant pseudofructopyranose sulfamates
US5507775A (en) * 1994-01-21 1996-04-16 Progressive Surgical Products Inc. Tissue expansion and approximation device
US5512291A (en) * 1992-01-13 1996-04-30 Li; Shu-Tung Method of making resorbable vascular wound dressing
US5512041A (en) * 1994-10-07 1996-04-30 Scott Health Care Wound dressing for promoting moist wound healing
US5519020A (en) * 1994-10-28 1996-05-21 The University Of Akron Polymeric wound healing accelerators
US5520926A (en) * 1992-03-17 1996-05-28 British Technology Group Limited Method of using mannose phosphates for the treatment of fibrotic disorders
US5522794A (en) * 1994-06-16 1996-06-04 Hercules Incorporated Method of treating human wounds
US5525335A (en) * 1992-04-21 1996-06-11 Ajinomoto Co., Inc. Wound healing agent
US5571521A (en) * 1984-01-16 1996-11-05 Lasker; Sigmund E. Composition containing silver ammonium phenytoin complex and a phenytoin and use of said composition
US5578022A (en) * 1995-04-12 1996-11-26 Scherson; Daniel A. Oxygen producing bandage and method
US5578310A (en) * 1992-04-23 1996-11-26 Berlex Laboratories Inc. Topical bioadhesive ointment compositions and their use in wound healing
US5602183A (en) * 1991-03-01 1997-02-11 Warner-Lambert Company Dermatological wound healing compositions and methods for preparing and using same
US5603946A (en) * 1993-10-08 1997-02-18 Bristol-Myers Squibb Company Wound dressing
US5610148A (en) * 1991-01-18 1997-03-11 University College London Macroscopically oriented cell adhesion protein for wound treatment
US5614561A (en) * 1991-03-01 1997-03-25 Warner-Lambert Company Antihistamine-wound healing compositions and methods for preparing and using same
US5629292A (en) * 1993-09-24 1997-05-13 The University Of Southern California Use of angiotensin III and analogs thereof in tissue repair
US5631019A (en) * 1994-02-17 1997-05-20 New York Blood Center, Inc. Biologic bioadhesive compositions containing fibrin glue and liposomes, methods of preparation and use
US5633285A (en) * 1991-03-01 1997-05-27 Warner-Lambert Company Cytoprotective wound healing compositions and methods for preparing and using same
US5632727A (en) * 1988-10-03 1997-05-27 Atrix Laboratories, Inc. Biodegradable film dressing and method for its formation
US5641814A (en) * 1991-03-01 1997-06-24 Warner-Lambert Company Antikeratolytic-wound healing compositions and methods for preparing and using same
US5646190A (en) * 1991-03-01 1997-07-08 Warner-Lambert Company Acne treating-wound healing compositions and methods for preparing and using same
US5648380A (en) * 1991-03-01 1997-07-15 Warner-Lambert Company Anti-inflammatory wound healing compositions and methods for preparing and using same
US5652274A (en) * 1991-03-01 1997-07-29 Martin; Alain Therapeutic-wound healing compositions and methods for preparing and using same
US5654461A (en) * 1995-11-02 1997-08-05 Yukong Limited Sulfamate compound containing carbamoyl group
US5658957A (en) * 1991-03-01 1997-08-19 Warner Lambert Company Immunostimulating wound healing compositions and method for preparing and using same
US5658956A (en) * 1991-03-01 1997-08-19 Warner-Lambert Company Bioadhesive-wound healing compositions and methods for preparing and using same
US5662904A (en) * 1991-03-28 1997-09-02 The Victoria University Of Manchester Anti-scarring compositions comprising growth factor neutralizing antibodies
US5662924A (en) * 1991-03-21 1997-09-02 Smith & Nephew Plc Wound dressing
US5663208A (en) * 1991-03-01 1997-09-02 Warner-Lambert Company Antifungal wound healing compositions and methods for preparing and using same
US5667501A (en) * 1992-12-08 1997-09-16 University College Cardiff Consultants Limited Wound dressings
US5674912A (en) * 1991-03-01 1997-10-07 Warner-Lambert Company Sunscreen-wound healing compositions and methods for preparing and using same
US5685834A (en) * 1994-07-29 1997-11-11 Barth; Alan H. Surgical dressing material
US5692302A (en) * 1991-03-01 1997-12-02 Warner-Lambert Company Razor cartridges comprising wound healing compositions and methods for preparing and using same
US5705477A (en) * 1982-09-24 1998-01-06 The United States Of America As Represented By The Department Of Health And Human Services Compositions of transforming growth factor β(TGF-β) which promotes wound healing and methods for their use
US5707647A (en) * 1994-04-08 1998-01-13 Atrix Laboratories, Inc. Adjunctive polymer system for use with medical device
US5713842A (en) * 1991-11-06 1998-02-03 Bioderm Occlusive wound dressing and applicator with same flexibility
US5716337A (en) * 1992-06-10 1998-02-10 Johnson & Johnson Medical, Inc. Absorbent product
US5716935A (en) * 1993-09-24 1998-02-10 University Of Southern California Use of antiotensin II analogs in tissue repair
US5735812A (en) * 1993-03-03 1998-04-07 Johnson & Johnson Medical, Inc. Water soluble wound dressing materials
US5759570A (en) * 1992-11-23 1998-06-02 Johnson & Johnson Medical, Inc. Multi-layer wound dressing
US5760006A (en) * 1997-06-23 1998-06-02 Ortho Pharmaceutical Corporation Anticonvulsant derivatives useful in treating psoriasis
US5780048A (en) * 1997-03-20 1998-07-14 Lee; Chung Chih First aid bandage dressing system and method of application thereof
US5804213A (en) * 1991-10-09 1998-09-08 Lectec Corporation Biologically active aqueous gel wound dressing
US5807341A (en) * 1996-12-11 1998-09-15 Team Medical Llc Medical catheter dressing device
US5807300A (en) * 1996-09-20 1998-09-15 Nix, Jr.; Frank H. Holder for wound dressing
US5834432A (en) * 1995-06-06 1998-11-10 The University Of Southern California Use of angiotensin II Type 2 receptor agonists in tissue repair
US5856245A (en) * 1988-03-14 1999-01-05 Nextec Applications, Inc. Articles of barrier webs
US5856364A (en) * 1991-03-01 1999-01-05 Warner Lambert Company Therapeutic antiviral-wound healing compositions and methods for preparing and using same
US5863938A (en) * 1991-03-01 1999-01-26 Warner Lambert Company Antibacterial-wound healing compositions and methods for preparing and using same
US5874479A (en) * 1991-03-01 1999-02-23 Warner-Lambert Company Therapeutic permeation enhanced-wound healing compositions and methods for preparing and using same
US5876743A (en) * 1995-03-21 1999-03-02 Den-Mat Corporation Biocompatible adhesion in tissue repair
US5892088A (en) * 1995-11-02 1999-04-06 Yukong Limited Sulfamate compound containing N-substituted carbamoyl group and method for preparing the same
US5897516A (en) * 1996-09-27 1999-04-27 Bristol-Myers Squibb Company Method of treating a wound by monitoring the swelling of a hydrocolloid layer in a wound dressing
US5902600A (en) * 1992-12-21 1999-05-11 Healthpoint, Ltd. Hydrogel polymer wound dressing
US5914125A (en) * 1991-02-07 1999-06-22 Ultra Laboratories Limited Wound dressing
US5955430A (en) * 1993-09-24 1999-09-21 University Of Southern California Use of angiotensin II fragments and analogs thereof in tissue repair
US5960795A (en) * 1993-07-16 1999-10-05 Tecnol Medical Products, Inc. Wound covering device
US5968001A (en) * 1996-05-14 1999-10-19 Bristol-Myers Squibb Company Wound dressings with leak prevention seal
US5972332A (en) * 1997-04-16 1999-10-26 The Regents Of The University Of Michigan Wound treatment with keratinocytes on a solid support enclosed in a porous material
US5977428A (en) * 1996-12-20 1999-11-02 Procyte Corporation Absorbent hydrogel particles and use thereof in wound dressings
USRE36370E (en) * 1992-01-13 1999-11-02 Li; Shu-Tung Resorbable vascular wound dressings
US5981606A (en) * 1991-03-01 1999-11-09 Warner-Lambert Company Therapeutic TGF-beta-wound healing compositions and methods for preparing and using same
US5989577A (en) * 1998-03-02 1999-11-23 Children's Hospital Medical Center Nontoxic vernix compositions and method of producing
US5998692A (en) * 1995-01-26 1999-12-07 Innovative Technologies Limited Wound dressing
US6022556A (en) * 1993-03-03 2000-02-08 Johnson & Johnson Medical, Inc. Swellable wound dressing materials
US6025150A (en) * 1996-11-21 2000-02-15 The Regents Of The University Of Michigan Methods and compositions for wound healing
US6033684A (en) * 1996-08-28 2000-03-07 Jonor, Inc. Compositions and methods for wound management
US6051249A (en) * 1995-01-27 2000-04-18 Coloplast A/S Dressing having a three-dimensional part and processes for the preparation of such a dressing
US6071537A (en) * 1996-06-28 2000-06-06 Ortho Pharmaceutical Corporation Anticonvulsant derivatives useful in treating obesity
US6087549A (en) * 1997-09-22 2000-07-11 Argentum International Multilayer laminate wound dressing
US6093388A (en) * 1996-08-12 2000-07-25 Btg International Limited Mannose-6-phosphate composition and its use in treating fibrotic disorders
US6124273A (en) * 1995-06-09 2000-09-26 Chitogenics, Inc. Chitin hydrogels, methods of their production and use
US6132759A (en) * 1996-05-03 2000-10-17 Innogenetics N.V. Medicaments containing gelatin cross-linked with oxidized polysaccharides
US6136341A (en) * 1998-02-27 2000-10-24 Petito; George D. Collagen containing tissue adhesive
US6142982A (en) * 1995-11-14 2000-11-07 Kci Medical Limited Portable wound treatment apparatus
US6143037A (en) * 1996-06-12 2000-11-07 The Regents Of The University Of Michigan Compositions and methods for coating medical devices

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US892088A (en) * 1907-09-26 1908-06-30 William Rich Marine fire-indicating system and extinguisher.
US5690795A (en) * 1995-06-05 1997-11-25 Applied Materials, Inc. Screwless shield assembly for vacuum processing chambers
US5753693A (en) 1996-06-28 1998-05-19 Ortho Pharmaceutical Corporation Anticonvulsant derivatives useful in treating manic-depressive bipolar disorder
HUP0001637A3 (en) * 1996-06-28 2002-04-29 Ortho Mcneil Pharm Inc The use of anticonvulsant derivatives for producing medicaments useful in treating psoriasis
US5753694A (en) * 1996-06-28 1998-05-19 Ortho Pharmaceutical Corporation Anticonvulsant derivatives useful in treating amyotrophic lateral sclerosis (ALS)
IL129276A (en) * 1996-10-08 2003-04-10 Ortho Mcneil Pharm Inc Anticonvulsant derivatives useful in treating neuropathic pain
WO2000000130A1 (en) 1998-06-29 2000-01-06 The Procter & Gamble Company Liquid transport member for high flux rates against gravity
WO2000010610A2 (en) 1998-08-19 2000-03-02 Theramark Limited Drug targeting
CA2348017C (en) * 1998-10-20 2005-07-19 Ortho-Mcneil Pharmaceutical, Inc. Anticonvulsant derivatives useful in treating alcohol dependency, addiction and abuse
ES2217819T3 (es) * 1998-11-17 2004-11-01 Ortho-Mcneil Pharmaceutical, Inc. Derivados anticonvulsivos para el tratamiento de transtornos de estres post-traumaticos.
PT1148874E (pt) 1999-02-01 2004-04-30 Ortho Mcneil Pharm Inc Uso de derivados anticonvulsivos para o tratamento da bulimia nervosa
NZ513724A (en) * 1999-02-17 2004-01-30 Ortho Mcneil Pharm Inc Anticonvulsant derivatives useful in treating essential tremor
NZ513643A (en) * 1999-02-24 2005-04-29 Univ Cincinnati Use of sulfamate derivatives for treating impulse control disorders
US6583172B1 (en) * 1999-04-08 2003-06-24 Richard P. Shank Anticonvulsant derivatives useful in treating chronic neurodegenerative disorders
ES2542868T3 (es) * 1999-06-14 2015-08-12 Vivus, Inc. Terapia de combinación para el tratamiento de diabetes asociada con la obesidad
US6515117B2 (en) 1999-10-12 2003-02-04 Bristol-Myers Squibb Company C-aryl glucoside SGLT2 inhibitors and method
WO2002043731A2 (en) * 2000-11-30 2002-06-06 University Of Florida Treatments for neurogenetic disorders, impulse control disorders, and wound healing
US6462084B1 (en) 2001-05-14 2002-10-08 Brookhaven Science Associates, Llc Treatment for obsessive-compulsive disorder (OCD) and OCD-related disorders using GVG
AU2003239455A1 (en) * 2002-05-14 2003-12-02 Ralph Ryback Method for treating dermatoses and tissue damage

Patent Citations (79)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5705477A (en) * 1982-09-24 1998-01-06 The United States Of America As Represented By The Department Of Health And Human Services Compositions of transforming growth factor β(TGF-β) which promotes wound healing and methods for their use
US4513006A (en) * 1983-09-26 1985-04-23 Mcneil Lab., Inc. Anticonvulsant sulfamate derivatives
US5571521A (en) * 1984-01-16 1996-11-05 Lasker; Sigmund E. Composition containing silver ammonium phenytoin complex and a phenytoin and use of said composition
US5856245A (en) * 1988-03-14 1999-01-05 Nextec Applications, Inc. Articles of barrier webs
US5632727A (en) * 1988-10-03 1997-05-27 Atrix Laboratories, Inc. Biodegradable film dressing and method for its formation
US5610148A (en) * 1991-01-18 1997-03-11 University College London Macroscopically oriented cell adhesion protein for wound treatment
US5914125A (en) * 1991-02-07 1999-06-22 Ultra Laboratories Limited Wound dressing
US5614561A (en) * 1991-03-01 1997-03-25 Warner-Lambert Company Antihistamine-wound healing compositions and methods for preparing and using same
US5658957A (en) * 1991-03-01 1997-08-19 Warner Lambert Company Immunostimulating wound healing compositions and method for preparing and using same
US5692302A (en) * 1991-03-01 1997-12-02 Warner-Lambert Company Razor cartridges comprising wound healing compositions and methods for preparing and using same
US5663208A (en) * 1991-03-01 1997-09-02 Warner-Lambert Company Antifungal wound healing compositions and methods for preparing and using same
US5863938A (en) * 1991-03-01 1999-01-26 Warner Lambert Company Antibacterial-wound healing compositions and methods for preparing and using same
US5652274A (en) * 1991-03-01 1997-07-29 Martin; Alain Therapeutic-wound healing compositions and methods for preparing and using same
US5602183A (en) * 1991-03-01 1997-02-11 Warner-Lambert Company Dermatological wound healing compositions and methods for preparing and using same
US5856364A (en) * 1991-03-01 1999-01-05 Warner Lambert Company Therapeutic antiviral-wound healing compositions and methods for preparing and using same
US5874479A (en) * 1991-03-01 1999-02-23 Warner-Lambert Company Therapeutic permeation enhanced-wound healing compositions and methods for preparing and using same
US5674912A (en) * 1991-03-01 1997-10-07 Warner-Lambert Company Sunscreen-wound healing compositions and methods for preparing and using same
US5648380A (en) * 1991-03-01 1997-07-15 Warner-Lambert Company Anti-inflammatory wound healing compositions and methods for preparing and using same
US5658956A (en) * 1991-03-01 1997-08-19 Warner-Lambert Company Bioadhesive-wound healing compositions and methods for preparing and using same
US5633285A (en) * 1991-03-01 1997-05-27 Warner-Lambert Company Cytoprotective wound healing compositions and methods for preparing and using same
US5981606A (en) * 1991-03-01 1999-11-09 Warner-Lambert Company Therapeutic TGF-beta-wound healing compositions and methods for preparing and using same
US5641814A (en) * 1991-03-01 1997-06-24 Warner-Lambert Company Antikeratolytic-wound healing compositions and methods for preparing and using same
US5646190A (en) * 1991-03-01 1997-07-08 Warner-Lambert Company Acne treating-wound healing compositions and methods for preparing and using same
US5662924A (en) * 1991-03-21 1997-09-02 Smith & Nephew Plc Wound dressing
US5662904A (en) * 1991-03-28 1997-09-02 The Victoria University Of Manchester Anti-scarring compositions comprising growth factor neutralizing antibodies
US5804213A (en) * 1991-10-09 1998-09-08 Lectec Corporation Biologically active aqueous gel wound dressing
US5713842A (en) * 1991-11-06 1998-02-03 Bioderm Occlusive wound dressing and applicator with same flexibility
USRE36370E (en) * 1992-01-13 1999-11-02 Li; Shu-Tung Resorbable vascular wound dressings
US5512291A (en) * 1992-01-13 1996-04-30 Li; Shu-Tung Method of making resorbable vascular wound dressing
US5520926A (en) * 1992-03-17 1996-05-28 British Technology Group Limited Method of using mannose phosphates for the treatment of fibrotic disorders
US5525335A (en) * 1992-04-21 1996-06-11 Ajinomoto Co., Inc. Wound healing agent
US5578310A (en) * 1992-04-23 1996-11-26 Berlex Laboratories Inc. Topical bioadhesive ointment compositions and their use in wound healing
US5716337A (en) * 1992-06-10 1998-02-10 Johnson & Johnson Medical, Inc. Absorbent product
US5759570A (en) * 1992-11-23 1998-06-02 Johnson & Johnson Medical, Inc. Multi-layer wound dressing
US5667501A (en) * 1992-12-08 1997-09-16 University College Cardiff Consultants Limited Wound dressings
US5902600A (en) * 1992-12-21 1999-05-11 Healthpoint, Ltd. Hydrogel polymer wound dressing
US5384327A (en) * 1992-12-22 1995-01-24 Mcneilab, Inc. Anticonvulsant sorbopyranose sulfamates
US6022556A (en) * 1993-03-03 2000-02-08 Johnson & Johnson Medical, Inc. Swellable wound dressing materials
US5735812A (en) * 1993-03-03 1998-04-07 Johnson & Johnson Medical, Inc. Water soluble wound dressing materials
US5960795A (en) * 1993-07-16 1999-10-05 Tecnol Medical Products, Inc. Wound covering device
US5716935A (en) * 1993-09-24 1998-02-10 University Of Southern California Use of antiotensin II analogs in tissue repair
US6096709A (en) * 1993-09-24 2000-08-01 University Of Southern California Use of angiotensin II fragments and analogs thereof in tissue repair
US5629292A (en) * 1993-09-24 1997-05-13 The University Of Southern California Use of angiotensin III and analogs thereof in tissue repair
US5955430A (en) * 1993-09-24 1999-09-21 University Of Southern California Use of angiotensin II fragments and analogs thereof in tissue repair
US5603946A (en) * 1993-10-08 1997-02-18 Bristol-Myers Squibb Company Wound dressing
US5498629A (en) * 1993-12-23 1996-03-12 Ortho Pharmaceutical Corporation Anticonvulsant pseudofructopyranose sulfamates
US5507775A (en) * 1994-01-21 1996-04-16 Progressive Surgical Products Inc. Tissue expansion and approximation device
US5631019A (en) * 1994-02-17 1997-05-20 New York Blood Center, Inc. Biologic bioadhesive compositions containing fibrin glue and liposomes, methods of preparation and use
US5707647A (en) * 1994-04-08 1998-01-13 Atrix Laboratories, Inc. Adjunctive polymer system for use with medical device
US5522794A (en) * 1994-06-16 1996-06-04 Hercules Incorporated Method of treating human wounds
US5685834A (en) * 1994-07-29 1997-11-11 Barth; Alan H. Surgical dressing material
US5512041A (en) * 1994-10-07 1996-04-30 Scott Health Care Wound dressing for promoting moist wound healing
US5519020A (en) * 1994-10-28 1996-05-21 The University Of Akron Polymeric wound healing accelerators
US5998692A (en) * 1995-01-26 1999-12-07 Innovative Technologies Limited Wound dressing
US6051249A (en) * 1995-01-27 2000-04-18 Coloplast A/S Dressing having a three-dimensional part and processes for the preparation of such a dressing
US5876743A (en) * 1995-03-21 1999-03-02 Den-Mat Corporation Biocompatible adhesion in tissue repair
US5578022A (en) * 1995-04-12 1996-11-26 Scherson; Daniel A. Oxygen producing bandage and method
US5834432A (en) * 1995-06-06 1998-11-10 The University Of Southern California Use of angiotensin II Type 2 receptor agonists in tissue repair
US6124273A (en) * 1995-06-09 2000-09-26 Chitogenics, Inc. Chitin hydrogels, methods of their production and use
US5892088A (en) * 1995-11-02 1999-04-06 Yukong Limited Sulfamate compound containing N-substituted carbamoyl group and method for preparing the same
US5654461A (en) * 1995-11-02 1997-08-05 Yukong Limited Sulfamate compound containing carbamoyl group
US6142982A (en) * 1995-11-14 2000-11-07 Kci Medical Limited Portable wound treatment apparatus
US6132759A (en) * 1996-05-03 2000-10-17 Innogenetics N.V. Medicaments containing gelatin cross-linked with oxidized polysaccharides
US5968001A (en) * 1996-05-14 1999-10-19 Bristol-Myers Squibb Company Wound dressings with leak prevention seal
US6143037A (en) * 1996-06-12 2000-11-07 The Regents Of The University Of Michigan Compositions and methods for coating medical devices
US6071537A (en) * 1996-06-28 2000-06-06 Ortho Pharmaceutical Corporation Anticonvulsant derivatives useful in treating obesity
US6093388A (en) * 1996-08-12 2000-07-25 Btg International Limited Mannose-6-phosphate composition and its use in treating fibrotic disorders
US6033684A (en) * 1996-08-28 2000-03-07 Jonor, Inc. Compositions and methods for wound management
US5807300A (en) * 1996-09-20 1998-09-15 Nix, Jr.; Frank H. Holder for wound dressing
US5897516A (en) * 1996-09-27 1999-04-27 Bristol-Myers Squibb Company Method of treating a wound by monitoring the swelling of a hydrocolloid layer in a wound dressing
US6025150A (en) * 1996-11-21 2000-02-15 The Regents Of The University Of Michigan Methods and compositions for wound healing
US5807341A (en) * 1996-12-11 1998-09-15 Team Medical Llc Medical catheter dressing device
US5977428A (en) * 1996-12-20 1999-11-02 Procyte Corporation Absorbent hydrogel particles and use thereof in wound dressings
US5780048A (en) * 1997-03-20 1998-07-14 Lee; Chung Chih First aid bandage dressing system and method of application thereof
US5972332A (en) * 1997-04-16 1999-10-26 The Regents Of The University Of Michigan Wound treatment with keratinocytes on a solid support enclosed in a porous material
US5760006A (en) * 1997-06-23 1998-06-02 Ortho Pharmaceutical Corporation Anticonvulsant derivatives useful in treating psoriasis
US6087549A (en) * 1997-09-22 2000-07-11 Argentum International Multilayer laminate wound dressing
US6136341A (en) * 1998-02-27 2000-10-24 Petito; George D. Collagen containing tissue adhesive
US5989577A (en) * 1998-03-02 1999-11-23 Children's Hospital Medical Center Nontoxic vernix compositions and method of producing

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US20020082222A1 (en) 2002-06-27
WO2002043731B1 (en) 2003-04-03
AU2002227052A1 (en) 2002-06-11
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ATE474572T1 (de) 2010-08-15
US8084491B2 (en) 2011-12-27

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