Therapeutic Treatment

• US 20140100249A1
• Filed: 10/04/2013
• Published: 04/10/2014
• Est. Priority Date: 10/09/2012
• Status: Active Application

• Current Assignee: Attentive Therapeutics, Inc.
• Original Assignee: Attentive Therapeutics, Inc.
• Inventors: Sears, Douglas, Reilly, Michael
• Application Number:
  US14/046,528
• Publication Number:
  US 20140100249A1
• Time in Patent Office: Days
• US Class Current: 514/325
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/4458 only substituted in position 2, e.g. methylphenidate
• CPC Class Codes: A61K 31/451 having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system

Abstract

This invention discloses a treatment for a patient receiving medication to treat an attention deficit disorder such as ADHD wherein the treatment results in a loss of appetite and impairment of the patient'"'"'s attentiveness. The treatment combines a treatment for an attention deficit disorder with an appetite stimulant, wherein the appetite stimulant increases the caloric intake of a patient, which can increase the patient'"'"'s attentiveness. The combination treatment can be given for an indefinite, including, without limitation, life-long, to allow a patient to maintain normal caloric intake during treatment for an attention deficit disorder.

Claims

1. A method of treating an individual with a disorder associated with an attention deficit disorder, the method comprises the step of administering to an individual in need thereof a pharmaceutical composition which comprises administration of a therapeutic compound to treat the attention deficit disorder and a therapeutic compound to treat a reduction in appetite, wherein administration reduces a symptom of a disorder associated with an attention deficit disorder and increases the attentiveness of the individual, thereby treating the individual.

2. The method of claim 1, wherein the attention deficit disorder is Attention Deficit Hyperactivity Disorder (ADHD).

3. The method of claim 1, wherein the therapeutic compound administered for the treatment of an attention deficit disorder is an amphetamine or a methylphenidate.

4. The method of claim 3, wherein the amphetamine or methylphenidate is selected from the group consisting of OROS methylphenidate (Concerta), dextroamphetamine immediate/sustained release (Adderall/Adderall XR), dexmethylphenidate (Focalin), Focalin XR, Metadate CD, Metadate ER, NWP09, Dexedrine, dextroamphetamine (Dexedrine), Dexedrine Spansules, Methylin ER (Ritalin SR), methylphenidate (Ritalin), and methylphenidate CR, Ritalin, Ritalin LA, SD-483, SPD-503, Ritalin SR, Intuniv ER, Intuniv, Methylin, Daytrana, Equasym, Dixirit, Kapvay, Daytrana Patch, Methylin chewable, Methylin liquid, Dextrostat, Strattera, Tenex, Catapres, Catapres TTS patch, Prozac, Serefam, Zoloft, Luvox, Paxil, Paxil CR, Pexeva, Celexa, Lexapro, Tofranil, Norpamin, Elavil, Pamelor, Sinequan, Anafranil, Wellbutrin, Wellbutrin SR, Wellbutrin XL, Effexor, Effexor XR, Remeron, Cymbalta, Nardil, Parnate, Emsam patch, Haldol, Orap, Prolixin, Mellaril, Thorazine, Stelazine, Moban, Loxitane, Risperdal, Zyprexa, Seroquel, Geodon, Abilify, Clozaril, Xanax, Xanax XR, Klonopin, Ativan, Buspar, Ambien CR, Ambien, Lunesta, Sonata, Rozerem, Lithiu, Lithobid, Eskalith, Depakote, Tegretol, Carbatrol, Trileptal, Lamictal, Topamax, Neurontin and the therapeutic compounds identified in Table 1.

5. The method according to claim 1, wherein the severity associated with attention deficit disorder is reduced by at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95%.

6. The method according to claim 4, wherein the dose of the therapeutic compound to treat the attention deficit disorder is in the range of at least 0.001 mg/kg/day, at least 0.01 mg/kg/day, at least 0.1 mg/kg/day, at least 1.0 mg/kg/day, at least 5.0 mg/kg/day, at least 10 mg/kg/day, at least 15 mg/kg/day, at least 20 mg/kg/day, at least 25 mg/kg/day, at least 30 mg/kg/day, at least 35 mg/kg/day, at least 40 mg/kg/day, at least 45 mg/kg/day, or at least 50 mg/kg/day.

7. The method according to claim 1, wherein the therapeutic compound to treat the attention deficit disorder is administered to an individual topical, sublingual, rectal, vaginal, trancutaneous, oral, inhaled, intranasal, subcutaneous, intravenous, enteral or parenteral.

8. The method of claim 1, wherein the therapeutic compound to treat a appetite reduction is an orexigenic drug.

9. The method of claim 8, wherein the orexigenic drug is selected from the group of:

alcohol, GHB, and other sedatives such as some benzodiazepine and nonbenzodiazepine tranquilizers and sleeping pills, anti-depressants (some SSRIs, Mianserin, etc.), 5-HT_2C receptor antagonists/inverse agonists (e.g., mirtazapine, mianserin, olanzapine, quetiapine, risperidone, amitriptyline, imipramine, cyproheptadine, etc.), H₁ receptor antagonists/inverse agonists (e.g., buclizine, mirtazapine, mianserin, olanzapine, quetiapine, n-3 fatty acids, amitriptyline, chlorpheniramine maleate, etc.), D₁/D₂ receptor antagonists (e.g., haloperidol, chlorpromazine, olanzapine, risperidone, quetiapine, etc.), Marinol, Megace, Megace ES, α

₁-adrenergic receptor antagonists (such as doxazosin, carvedilol, propanolol, colonidine), Serefam, α

₂-adrenergic receptor agonists (e.g., clonidine, guanfacine, etc.), some beta blockers such as propanolol, natural or synthetic CB, receptor agonists (e.g., THC or dronabinol (found in Cannabis), tetrahydrocannibinol, diphenydramine, promethazine, B vitamin supplements, nabilone, JWH-018 etc.), Corticosteroids (e.g. prednisone or dexamethasone), Sodium valproate (Depakote), Megestrol, Pregabalin, Sulfonylurea antidiabetic drugs such as glibenclamide and chlorpropamide, steroids (including, without limitation, boldenone, oxymetholone, dexamethasone, or methandrostenolone, prednisone, hydrocortisone, oxandrolone, nandrolone, testosterone), some kappa opioid receptor agonists such as tifluadom, hormones such as mederoxyprogesteronemirtazapine (Remeron), a tetracyclic antidepressant;

cyproheptadine (Periactin), an antihistamine;

nandrolone, oxymetholone, and oxandrolone (Anadrol-50, Durabolin, Hybolin, anti-IL6 antibody, selective androgen receptor modulator (“

SARM”

), Oxandrin, and other brand names), VT-122 (a coadministration of propranolol and etodolac), type 4 melanocortin receptor antagonis, IL6 antagonist, synthetic ghrelin, myostatin decoy receptor, fast skeletal muscle troponin-activating substance, anticatabolic/anabolic transforming agent MT-102, celecoxib, testosterone, vitamin D, OHR/AVR118, soluble version of the ActRIIB receptor, 5-HT₃ antagonists, Cox-2 inhibitor, thalidomide, omega-3 fatty acids, anticyclooxygenase-2 drugs and megestrol acetate (Megace). In addition to these prescription drugs, fish oil (eicosapentaenoic acid or EPA), EATMOR, other vitamins and natural or artificial appetite stimulants.

10. The method of claim 8, wherein the orexigenic drug is cyproheptadine hydrochloride.

11. The method according to claim 1, wherein the symptoms associated with appetite reduction is reduced by at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95%.

12. The method according claim 1, wherein the treatment for appetite reduction results in an increase in weight by at least 0.5 pounds, at least 1 pound, at least 1.5 pounds, at least 2 pounds, at least 2.5 pounds, at least 3 pounds, at least 3.5 pounds, at least 4 pounds, at least 4.5 pounds, at least 5 pounds, at least 5.5 pounds, at least 6 pounds, at least 6.5 pounds, at least 7 pounds, at least 7.5 pounds, at least 8 pounds, at least 8.5 pounds, at least 9 pounds, at least 9.5 pounds, at least 10 pounds, at least 10.5 pounds, at least 11 pounds, at least 11.5 pounds, at least 12 pounds, at least 12.5 pounds, at least 13 pounds, at least 13.5 pounds, at least 14 pounds, at least 14.5 pounds, at least 15 pounds, at least 20 pounds, at least 25 pounds, at least 30 pounds, at least 50 pounds. In another embodiment, a therapeutic compound disclosed herein for the treatment of appetite reduction results in an increase in weight by, e.g., from 0.5 pounds to 50 pounds, from 0.5 pounds to 30 pounds, from 0.5 pounds to 25 pounds, from 0.5 pounds to 20 pounds, from 0.5 pounds to 15 pounds, from 0.5 pounds to ten pounds, from 0.5 pounds to 7.5 pounds, from 0.5 pounds to 5 pounds, from 1 pound to 15 pounds, from 1 pound to 10 pounds, from 1 pound to 7.5 pounds, form 1 pound to 5 pounds, from 2 pounds to ten pounds, from 2 pounds to 7.5 pounds.

13. The method according to claim 1, wherein the therapeutic compound to treat the reduction in appetite is administered to an individual topical, sublingual, rectal, vaginal, trancutaneous, oral, inhaled, intranasal, subcutaneous, intravenous, enteral or parenteral.

14. The method of claim 1, wherein an increase in attentiveness is measured by CGI-I and the method results in a reduction in the CGI-I score by at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90% or at least 95%.

15. A pharmaceutical composition comprising a therapeutic compound for a disorder associated with an attention deficit disorder and a therapeutic compound for a disorder associated with a reduction in appetite, wherein the pharmaceutical composition reduces a symptom of a disorder associated with an attention deficit disorder and increases the attentiveness of the individual, thereby treating the individual.

16. A pharmaceutical composition of claim 15, wherein the attention deficit disorder is Attention Deficit Hyperactivity Disorder (ADHD).

17. A pharmaceutical composition of claim 15, wherein the therapeutic compound administered for the treatment of an attention deficit disorder is an amphetamine or a methylphenidate.

18. A pharmaceutical composition of claim 17, wherein the amphetamine or methylphenidate is selected from the group consisting of OROS methylphenidate (Concerta), dextroamphetamine immediate/sustained release (Adderall/Adderall XR), dexmethylphenidate (Focalin), Focalin XR, Metadate CD, Metadate ER, NWP09, Dexedrine, dextroamphetamine (Dexedrine), Dexedrine Spansules, Methylin ER (Ritalin SR), methylphenidate (Ritalin), and methylphenidate CR, Ritalin, Ritalin LA, SD-483, SPD-503, Ritalin SR, Intuniv ER, Intuniv, Methylin, Daytrana, Equasym, Dixirit, Kapvay, Daytrana Patch, Methylin chewable, Methylin liquid, Dextrostat, Strattera, Tenex, Catapres, Catapres TTS patch, Prozac, Serefam, Zoloft, Luvox, Paxil, Paxil CR, Pexeva, Celexa, Lexapro, Tofranil, Norpamin, Elavil, Pamelor, Sinequan, Anafranil, Wellbutrin, Wellbutrin SR, Wellbutrin XL, Effexor, Effexor XR, Remeron, Cymbalta, Nardil, Parnate, Emsam patch, Haldol, Orap, Prolixin, Mellaril, Thorazine, Stelazine, Moban, Loxitane, Risperdal, Zyprexa, Seroquel, Geodon, Abilify, Clozaril, Xanax, Xanax XR, Klonopin, Ativan, Buspar, Ambien CR, Ambien, Lunesta, Sonata, Rozerem, Lithiu, Lithobid, Eskalith, Depakote, Tegretol, Carbatrol, Trileptal, Lamictal, Topamax, Neurontin and the therapeutic compounds identified in Table 1.

19. A pharmaceutical composition according to claim 15, wherein the severity associated with attention deficit disorder is reduced by at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95%.

20. A pharmaceutical composition according to claim 15, wherein the symptoms associated with attention deficit disorder is reduced by about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, about 80% to about 100%, about 10% to about 90%, about 20% to about 90%, about 30% to about 90%, about 40% to about 90%, about 50% to about 90%, about 60% to about 90%, about 70% to about 90%, about 10% to about 80%, about 20% to about 80%, about 30% to about 80%, about 40% to about 80%, about 50% to about 80%, or about 60% to about 80%, about 10% to about 70%, about 20% to about 70%, about 30% to about 70%, about 40% to about 70%, or about 50% to about 70%.

21. A pharmaceutical composition according to claim 15, wherein the dose of the therapeutic compound to treat the attention deficit disorder is in the range of about 0.001 mg/kg/day to about 10 mg/kg/day, about 0.001 mg/kg/day to about 15 mg/kg/day, about 0.001 mg/kg/day to about 20 mg/kg/day, about 0.001 mg/kg/day to about 25 mg/kg/day, about 0.001 mg/kg/day to about 30 mg/kg/day, about 0.001 mg/kg/day to about 35 mg/kg/day, about 0.001 mg/kg/day to about 40 mg/kg/day, about 0.001 mg/kg/day to about 45 mg/kg/day, about 0.001 mg/kg/day to about 50 mg/kg/day, about 0.001 mg/kg/day to about 75 mg/kg/day, or about 0.001 mg/kg/day to about 100 mg/kg/day.

22. A pharmaceutical composition according to any one of claim 15, wherein the therapeutic compound to treat the attention deficit disorder is administered to an individual topical, sublingual, rectal, vaginal, trancutaneous, oral, inhaled, intranasal, subcutaneous, intravenous, enteral or parenteral.

23. A pharmaceutical composition according to claim 15, wherein the orexigenic drug is selected from the group of:

alcohol, GHB, and other sedatives such as some benzodiazepine and nonbenzodiazepine tranquilizers and sleeping pills, anti-depressants (some SSRIs, Mianserin, etc.), 5-HT_2C receptor antagonists/inverse agonists (e.g., mirtazapine, mianserin, olanzapine, quetiapine, risperidone, amitriptyline, imipramine, cyproheptadine, etc.), H₁ receptor antagonists/inverse agonists (e.g., buclizine, mirtazapine, mianserin, olanzapine, quetiapine, n-3 fatty acids, amitriptyline, chlorpheniramine maleate, etc.), D₁/D₂ receptor antagonists (e.g., haloperidol, chlorpromazine, olanzapine, risperidone, quetiapine, etc.), Marinol, Megace, Megace ES, α

₁-adrenergic receptor antagonists (such as doxazosin, carvedilol, propanolol, colonidine), Serefam, α

₂-adrenergic receptor agonists (e.g., clonidine, guanfacine, etc.), some beta blockers such as propanolol, natural or synthetic CB, receptor agonists (e.g., THC or dronabinol (found in Cannabis), tetrahydrocannibinol, diphenydramine, promethazine, B vitamin supplements, nabilone, JWH-018 etc.), Corticosteroids (e.g. prednisone or dexamethasone), Sodium valproate (Depakote), Megestrol, Pregabalin, Sulfonylurea antidiabetic drugs such as glibenclamide and chlorpropamide, steroids (including, without limitation, boldenone, oxymetholone, dexamethasone, or methandrostenolone, prednisone, hydrocortisone, oxandrolone, nandrolone, testosterone), some kappa opioid receptor agonists such as tifluadom, hormones such as mederoxyprogesteronemirtazapine (Remeron), a tetracyclic antidepressant;

cyproheptadine (Periactin), an antihistamine;

nandrolone, oxymetholone, and oxandrolone (Anadrol-50, Durabolin, Hybolin, anti-IL6 antibody, selective androgen receptor modulator (“

SARM”

), Oxandrin, and other brand names), VT-122 (a coadministration of propranolol and etodolac), type 4 melanocortin receptor antagonis, IL6 antagonist, synthetic ghrelin, myostatin decoy receptor, fast skeletal muscle troponin-activating substance, anticatabolic/anabolic transforming agent MT-102, celecoxib, testosterone, vitamin D, OHR/AVR118, soluble version of the ActRIIB receptor, 5-HT₃ antagonists, Cox-2 inhibitor, thalidomide, omega-3 fatty acids, anticyclooxygenase-2 drugs and megestrol acetate (Megace). In addition to these prescription drugs, fish oil (eicosapentaenoic acid or EPA), EATMOR, other vitamins and natural or artificial appetite stimulants.

24. A pharmaceutical composition according to claim 15, wherein the orexigenic drug is cyproheptadine hydrochloride.

25. A pharmaceutical composition according to claim 15, wherein the treatment for appetite reduction results in an increase in weight by at least 0.5 pounds, at least 1 pound, at least 1.5 pounds, at least 2 pounds, at least 2.5 pounds, at least 3 pounds, at least 3.5 pounds, at least 4 pounds, at least 4.5 pounds, at least 5 pounds, at least 5.5 pounds, at least 6 pounds, at least 6.5 pounds, at least 7 pounds, at least 7.5 pounds, at least 8 pounds, at least 8.5 pounds, at least 9 pounds, at least 9.5 pounds, at least 10 pounds, at least 10.5 pounds, at least 11 pounds, at least 11.5 pounds, at least 12 pounds, at least 12.5 pounds, at least 13 pounds, at least 13.5 pounds, at least 14 pounds, at least 14.5 pounds, at least 15 pounds, at least 20 pounds, at least 25 pounds, at least 30 pounds, at least 50 pounds. In another embodiment, a therapeutic compound disclosed herein for the treatment of appetite reduction results in an increase in weight by, e.g., from 0.5 pounds to 50 pounds, from 0.5 pounds to 30 pounds, from 0.5 pounds to 25 pounds, from 0.5 pounds to 20 pounds, from 0.5 pounds to 15 pounds, from 0.5 pounds to ten pounds, from 0.5 pounds to 7.5 pounds, from 0.5 pounds to 5 pounds, from 1 pound to 15 pounds, from 1 pound to 10 pounds, from 1 pound to 7.5 pounds, form 1 pound to 5 pounds, from 2 pounds to ten pounds, from 2 pounds to 7.5 pounds.