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WO2025245066A1 - Compositions et méthodes pour influer sur la perte de poids, la gestion du poids, les troubles sexuels, le bien-être, l'estime de soi et/ou la confiance en soi - Google Patents

Compositions et méthodes pour influer sur la perte de poids, la gestion du poids, les troubles sexuels, le bien-être, l'estime de soi et/ou la confiance en soi

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Publication number
WO2025245066A1
WO2025245066A1 PCT/US2025/030126 US2025030126W WO2025245066A1 WO 2025245066 A1 WO2025245066 A1 WO 2025245066A1 US 2025030126 W US2025030126 W US 2025030126W WO 2025245066 A1 WO2025245066 A1 WO 2025245066A1
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weight
self
compound
bupropion
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Robert E. Pyke
Nicolas G. Sitchon
John F. Kaufmann
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S1 BIOPHARMA Inc
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S1 BIOPHARMA Inc
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  • the present invention relates to pharmaceutical combinations comprising bupropion and trazodone and methods of using the same for affecting weight loss in subjects who may be obese, overweight or desire to lose undesirable or unwanted weight.
  • the present invention also relates to pharmaceutical combinations comprising bupropion and trazodone and methods of using the same for inducing weight loss, effectuating weight management, improving a sexual disorder, and/or improving low or poor or a lack of a subjective state of well-being, self-esteem, and/or self-confidence in subjects who may be obese, overweight or desire to lose undesirable or unwanted weight or who want to maintain weight.
  • the present invention also relates to pharmaceutical combinations comprising bupropion and trazodone and methods of using the same for weight loss and/or weight maintenance management.
  • Obesity is defined as having a high body mass index (BMI).
  • BMI body mass index
  • Obesity is frequently subdivided into categories (a) Class 1: BMI of 30 to ⁇ 35, (b) Class 2: BMI of 35 to ⁇ 40, and (3) Class 3: BMI of 40 or higher. Class 3 obesity is sometimes categorized as “severe” obesity. See Defining Adult Overweight & Obesity, Centers for Disease Control and Centers (CDC), June 3, 2022, available online at https://www.cdc.gov/obesity/basics/adult-defining.html. [007] Obesity is one of the leading risk factors for early death and is responsible for millions of premature deaths each year. Obesity is a cardiometabolic risk factor for heart disease, stroke, diabetes, and various types of cancer.
  • Obesity contributes to cardiovascular risk factors such as dyslipidemia, Type 2 diabetes, hypertension, sleep disorders, coronary heart disease, stroke, diabetes, asthma, high cholesterol, osteoarthritis and various types of cancer. See Powell-Wiley TM, et al.; American heart association council on lifestyle and cardiometabolic health; council on cardiovascular and stroke nursing; council on clinical cardiology; council on epidemiology and prevention; and stroke council. obesity and cardiovascular disease: a scientific statement from the american heart association. Circulation. 2021;143(21):e984-e1010.
  • CDC FastStats also reports that 41.9% of adults aged 20 and over have obesity, and 73.6% are overweight, including obesity. See Obesity and Overweight, Disease Control and Centers (CDC), January 5, 2023, available online at https://www.cdc.gov/nchs/fastats/obesity-overweight.htm. Attorney Docket No.49848-4030PCT [0014] Also sweeping the US is an obesity drug boom. This obesity drug boom has upended the entire health industry with skyrocketing demands and costs for glucagon- like peptide 1 (GLP-1) drugs and GLP-1/GIP (glucose-dependent insulinotropic polypeptide agonist) combination drugs for weight loss treatment.
  • GLP-1 glucagon- like peptide 1
  • GLP-1/GIP glucose-dependent insulinotropic polypeptide agonist
  • Ozempic® and Wegovy® two semaglutide injectable products, are made by Novo Nordisk.
  • Wegovy® are the same injectable drug, semaglutide, but they are marketed under two different names.
  • Ozempic® and Wegovy® are the same drug, they are approved by the FDA for different indications.
  • Ozempic® (semaglutide) is FDA-approved for the treatment of type 2 diabetes mellitus and to reduce the risk of major adverse cardiovascular events. See Ozempic® FDA-approved label, available online at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/209637s020s021lbl.pdf. weight management.
  • Monjauro® (tirzepatide) and Zepbound® (tirzepatide) are also the same injectable drug, and they also have been approved by the FDA for different indications. Monjauro® (tirzepatide) is FDA-approved for the treatment of type 2 diabetes mellitus, whereas Zepbound® (tirzepatide) is FDA-approved for the treatment of chronic weight management.
  • GLP-1 drugs are incretin drugs that mimic the native incretin metabolic hormones, GLP-1 and GIP.
  • GLP-1 drugs as used herein also includes AMG-133 (maridebart cafraglutide), a combination drug wherein a GIP receptor antibody is linked to two GLP-1 agonists. They work by slowing gastric emptying, decreasing appetite, and improving glycemic control.
  • Ozempic® and Wegovy® mimic the incretin hormone GLP-1, which lowers blood sugar.
  • Mounjaro® and Zepbound® Attorney Docket No.49848-4030PCT mimic the incretin hormones GLP-1 and GIP, which also lower blood sugar.
  • GLP-1 drugs for weight loss is not without risk. GLP-1 use in some cases is associated with pancreatitis, intestinal obstruction, biliary disease and adverse gastrointestinal effects, such as nausea, vomiting, constipation, and diarrhea.
  • GLP-1 agonists from 2 daily injections to 1 per week and beyond, diaTribe Learn, January 10, 2018, updated on August 14, 2021, available online at https://diatribe.org/diabetes- medications/glp-1-agonists-2-daily-injections-1-week-and- these in [0033]
  • GLP-1 drugs raise the question of whether the GLP-1 drugs can provide a real and sustainable weight loss solution for people requiring weight loss medication and chronic weight loss management.
  • U.S. Pat. Nos. 7,056,890 and 7,659,256 discloses a composition comprising phentermine and topiramate and its use for effectuating weight loss.
  • a fixed dose combination of bupropion and naltrexone has been approved in the United States by the FDA for affecting weight loss, suppressing appetite and/or treating obesity-related conditions.
  • the product is marketed in the United States by Takeda Pharmaceuticals under the brand name Contrave®.
  • the product is in the form of a sustained release tri-layer tablet containing subject layers of bupropion and naltrexone separated by a sugar-containing intermediate layer. Bupropion is used as an antidepressant.
  • Naltrexone is an opioid antagonist. It is a synthetic congener of oxymorphone with no opioid agonist properties.
  • the bupropion and naltrexone combination has effects on two separate areas of the brain involved in the regulation of food intake: the hypothalamus (appetite regulatory center) and the mesolimbic dopamine circuit (reward system). The exact neurochemical effects of the combination leading to weight loss however are not fully understood.
  • U.S. Pat. Nos.7,375,111; 7,462,626 and 8,722,085 disclose use of combinations of bupropion and naltrexone for the treatment of being overweight and obesity.
  • U.S. Pat. Nos. 8,088,786 and 8,318,788 disclose a layered composition of bupropion and naltrexone in which the two drug layers are separated by an intermediate layer containing sugar as well as a method of affecting weight loss by administering said composition. Such composition requires complicated manufacturing processes, commercial manufacturing of which in turn consumes significant amount of time and is cost intensive.
  • U.S. Pat. Nos. 7,375,111 and 7,462,626 disclose the combination of naltrexone and bupropion for weight loss therapy. Attorney Docket No.49848-4030PCT [0043] U.S. Pat.
  • SD sexual disorder or sexual dysfunction
  • FSD female sexual dysfunction
  • MSD male sexual dysfunction
  • FSD Female Sexual Dysfunction
  • FSD includes numerous subtypes, namely, hypoactive sexual desire disorder (“HSDD”), female sexual arousal disorder (“FSAD”), female orgasmic disorder (“FOD”) and female sexual pain disorder (FPD”).
  • HSDD hypoactive sexual desire disorder
  • FSAD female sexual arousal disorder
  • FOD female orgasmic disorder
  • FPD female sexual pain disorder
  • HSDD low sexual disorder
  • DSM-IV-TR defined herein after
  • the presence of distress or interpersonal difficulty is an integral part of HSDD and is central to the Attorney Docket No.49848-4030PCT diagnosis of the condition. Approximately 1 in 10 women reported low sexual desire with associated distress, which may be HSDD.
  • FSAD or sexual arousal disorder involves women whose desire for sex might be intact, but they have difficulty with arousal or are unable to become aroused or maintain arousal during sexual activity.
  • FOD or orgasmic disorder You have persistent or recurrent difficulty in achieving orgasm after sufficient sexual arousal and ongoing stimulation.
  • FSPD or sexual pain disorder involves women who have pain associated with sexual stimulation or vaginal contact. See, for example, Female dysfunction, Diseases and Conditions, Mayo Clinic, available online at https://www.mayoclinic.org/diseases-conditions/female-sexual-dysfunction/symptoms- [0048] HSDD as discussed above concerns "a deficiency or absence of sexual fantasies and desire for sexual activity.
  • HSDD is defined as an absence or marked reduction in desire or motivation to engage in sexual activity as manifested by any of the following: 1) reduced or absent spontaneous desire (sexual thoughts or fantasies); 2) reduced or absent responsive desire to erotic cues and stimulation; or 3) inability to sustain desire or interest during sexual activity.
  • the pattern is persistent or recurrent over a period of at least several months and occurs frequently, though may fluctuate in severity, and is not secondary to a sexual pain disorder.
  • HSDD is one of, if not, the most common sexual dysfunction problems presented today to clinicians for diagnosis and treatment. HSDD affects men and women of all ages. According to myVMC, it is estimated that approximately 20% of men and 33% of women are affected by low or absent sexual desire.
  • Addyi (flibanserin) is a serotonin 1A receptor agonist and a serotonin 2A receptor antagonist. See, for example, Clayton AH, Kingsberg SA, Goldstein I; Evaluation and management of hypoactive sexual desire disorder. Sex Med.2018;6(2):59-74.
  • Addyi® (flibanserin) on average, only about 10% more patients treated with Addyi® than placebo reported clinically meaningful improvement, i.e., about one satisfying sexual event per month compared to a placebo.
  • Addyi® (flibanserin) is not without risk, however. About 1 in 6 women who take Addyi® (flibanserin) experience clinically significant hypotension and syncope, which side effects are exacerbated by alcohol consumption.
  • HSDD Hypoactive Sexual Desire Disorder in Premenopausal Women. Am Fam Physician.2016;93(10):826-828; and Simon JA, et al.; Clinically meaningful benefit in women with hypoactive sexual desire disorder treated with flibanserin. Sex Med.2022;10(1):100476. [0051] HSDD can have serious deleterious effects on the overall health of women, their quality of life, and the well-being of their personal relationships.
  • FSAD Another a subtype of female sexual dysfunction that is characterized by physiological findings or damage to the gynecological system. FSAD generally involves women are distressed due to their inability to attain or maintain adequate vaginal lubrication. Low or lack of vaginal estrogen, arterial insufficiency, tactile insensitivity and/or relationship conflicts are common causes of FSAD.
  • Typical treatments include hormone therapies, e.g., testosterone or estrogen patches, pills, and topical creams, and anxiety or depression therapy that may have sexual side effects.
  • hormone therapies e.g., testosterone or estrogen patches, pills, and topical creams
  • anxiety or depression therapy that may have sexual side effects.
  • estrogen is believed to improve vaginal tone and elasticity, increase vaginal blood flow, and enhance lubrication.
  • Feldhaus-Dahir M The physiology and causes of female sexual arousal disorder: part I. Ural Nurs. 2009 Nov-Dec;29(6):440-3.
  • PMID 20088237.
  • FOD involves orgasm that is absent, infrequent, markedly diminished in intensity, or markedly delayed in response to stimulation despite normal levels of subjective arousal. Conn , Hodges, KR. Female Orgasmic Disorder. Merck Manual Professional Version.
  • FSP disorders is believed to affect about 15% of women.
  • FSD involves women who experience chronic and/or intermittent pain in and/or around the vulva, vagina, or uterus.
  • Symptoms commonly associated with FSP may include chronic pelvic pain, vaginismus (tightening of the vaginal muscles upon penetration), dyspareunia (pain during sex), and vulvodynia (pain in the vulva).
  • FSP can negatively impact women in daily functioning, sexual satisfaction, and relationships.
  • FSIAD is a condition that generally concerns older and/or postmenopausal women. FSIAD symptoms include a lack of or significantly reduced sexual interest/arousal which can lead to distress and/or interpersonal difficulties. See, for example, Adebisi OY, Carlson K. Female Sexual Interest and Arousal Disorder. [Updated 2024 Oct 29]. In: StatPearls [Internet].
  • MSD is a series or group of conditions that affect male sexual functioning. Common MSDs include erectile dysfunction (ED), Peyronie’s disease (PD), premature ejaculation (PE), delayed ejaculation, decreased libido, sexually transmitted infections (STIs), and dry orgasm, defined by impaired sexual functioning. MSD also includes male hypoactive sexual desire disorder (“MHSDD”).
  • ED erectile dysfunction
  • PD Peyronie’s disease
  • PE premature ejaculation
  • STIs sexually transmitted infections
  • MHSDD male hypoactive sexual desire disorder
  • MHSDD is defined in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, 2013 (DSM-5), as persistent or recurrently deficient sexual or erotic thoughts, generies, and desire for sexual activity.
  • Other common symptoms of MHSDD include little to no sex drive, reduced interest in sex and sexual activities, unaroused by visual or sexual stimulation, inability to experience spontaneous desire, decreased interest in self-pleasure, i.e., masturbation, and loss of erectile/ejaculatory function. These symptoms must have persisted for a minimum of six Attorney Docket No.49848-4030PCT months, and they must cause clinically significant distress.
  • the disorder is specified by severity level and subtyped into lifelong versus acquired, generalized versus situational.
  • MSD prevalence increases with age and is higher in more than 50% of men who are between the ages of 40 and 70, who typically describe some degree of erectile dysfunction. See, for example, Anderson D, Laforge J, Ross MM, Van GmbHdonck R, Hasoon J, Viswanath O, Kaye AD, Urits I. Male Sexual Dysfunction. Health Psychol Res. 2022 Aug 20;10(3):37533. doi: 10.52965/001c.37533. PMID: 35999971; PMCID: PMC9392840, and Male sexual problems. Health Direct, available online at https://www.healthdirect.gov.au/male-sexual-problems.
  • Bupropion is an atypical antidepressant of the aminoketone group, structurally related to cathinone, an amphetamine-like stimulant. Bupropion is metabolized in the liver and its major active metabolites, hydroxybupropion, threohydrobupropion, and erythrohydrobupropion, have higher plasma concentrations than bupropion. While the mechanism of action of bupropion is not completely understood, bupropion and its major metabolites are believed to exert their effects by inhibiting dopamine and norepinephrine reuptake and by blocking several nicotinic receptors in the brain.
  • bupropion primarily acts through the norepinephrine Attorney Docket No.49848-4030PCT transporter (“NET”) and the dopamine transporter (“DAT”) with additional cytochrome P450 2D6 (CYP450 2D6) inhibition.
  • NET norepinephrine Attorney Docket No.49848-4030PCT transporter
  • DAT dopamine transporter
  • CYP450 2D6 cytochrome P450 2D6
  • Bupropion is the only synthetic cathinone approved by the FDA. Bupropion is related to phenylethylamines and is similar in structure to cathinone, an amphetamine- like stimulant, as indicated above, and diethylpropion, an appetite suppressant and sympathomimetic agent.
  • VMAT-2 vesicular monoamine transporter-2
  • Bupropion is also believed to have similar mechanisms of action to diethylpropion in the CNS to boost norepinephrine and dopamine levels. These chemicals are believed to act on the brain's appetite center in the hypothalamus to reduce appetite. Bupropion is an antidepressant and smoking cessation agent, while diethylpropion is an appetite suppressant used to treat obesity in the short-term management of obesity, along with dietary and lifestyle changes. See Arias HR, Santamar ⁇ a A, Ali SF; Pharmacological and neurotoxicological actions mediated by bupropion and diethylpropion. Int Rev Neurobiol. 2009;88:223-55.
  • Trazodone inhibits serotonin transporter, serotonin type 2 receptors and the reuptake of serotonin. Trazodone also blocks histamine and alpha-1-adrenergic receptors and induces significant changes in 5-HT presynaptic receptor adrenoreceptors. Trazodone lowers levels of neurotransmitters associated with arousal effects, such as serotonin, noradrenaline, dopamine, acetylcholine, and histamine.
  • weight loss drugs that provide alternative options to other weight loss drugs, like the GLP-1 drugs, for chronic weight loss management after discontinued use of other weight loss drugs, such as the GLP-1 drugs, for improving sexual desire, sexual function, subjective state of well- being, self-esteem, and/or self-confidence while affecting weight loss and/or effectuating weight management.
  • GLP-1 drugs a pharmaceutically acceptable salt thereof
  • the second compound is trazodone, or a pharmaceutically acceptable salt thereof.
  • the combination is preferably an oral, non-hormonal, preferably, a fixed-dose combination of sustained release bupropion, or its pharmaceutically acceptable salt, and sustained release trazodone, or its pharmaceutically acceptable salt.
  • Attorney Docket No.49848-4030PCT [0065] Also disclosed herein are methods of providing obesity or weight loss therapy or weight loss maintenance therapy. [0066] More particularly, disclosed are methods for treating obese subjects, treating subjects who are not obese but overweight, treating subjects who desire to lose weight, inducing weight loss, affecting weight, chronic maintenance of weight loss, enhancing energy, improving sleep, improving sexual desire and sexual function, improving subjective state of well-being, self-esteem, and/or self-confidence.
  • methods of providing weight loss therapy particularly for subjects suffering from being overweight or obese are disclosed.
  • the combination of bupropion and trazodone unexpectedly induces weight loss in subjects suffering from being overweight or obese or who desire to lose weight
  • the combination of sustained release (SR) bupropion and sustained release (SR) trazodone were highly tolerable with minimal side effects and, quite surprisingly and unexpectedly, the combination induced weight loss in about 71% of the patients and demonstrated about a 38% stronger HSDD efficacy than the use of bupropion alone.
  • the combination of bupropion and trazodone unexpectedly treats and induces weight loss in patients suffering from being overweight, being obese or carrying undesirable weight and improves their sexual dysfunction or disorder, e.g., low of no sexual desire, low or no sexual fantasies, low or no sexual arousal, and/or orgasmic dysfunction, i.e., a diminished frequency and/or intensity in orgasms.
  • the combination of bupropion and trazodone unexpectedly treats and induces weight loss in patients suffering from being overweight, being obese or carrying undesirable weight and improves their sense of subjective well-being, self- esteem, and/or self-confidence after weight loss, wherein their low, poor or lack of subjective well-being, self-esteem, and/or self-confidence was due to being obese, being overweight or carrying undesirable weight.
  • the combination of bupropion and trazodone unexpectedly treats and induces weight loss in patients suffering from being overweight, being obese or carrying undesirable weight and improves their sense of subjective well-being, self- esteem, and/or self-confidence due to improved energy and sleep.
  • the combination of bupropion and trazodone unexpectedly treats and induces weight loss in patients suffering from being overweight, being obese or carrying undesirable weight, improves their sexual dysfunction or disorder, e.g., low of no sexual desire, low or no sexual fantasies, low or no sexual arousal, and orgasmic dysfunction, i.e., a diminished frequency and/or intensity in orgasms, and improves their sense of subjective well-being after weight loss and having improvements in the their sexual dysfunction or disorder.
  • the combination of bupropion and trazodone unexpectedly treats and improves both overweight, obesity or weight loss and sexual dysfunction or disorder (SD”).
  • the combination of bupropion and trazodone unexpectedly treats and improves both overweight, obesity or weight loss and subjective well-being, self-esteem, and/or self-confidence.
  • the combination of bupropion and trazodone unexpectedly treats and improves both overweight, obesity or weight loss and sexual dysfunction or disorder (SD”) and subjective well-being, self-esteem, and/or self-confidence.
  • SD sexual dysfunction or disorder
  • the combination of bupropion and trazodone unexpectedly treats and improves both overweight, obesity or weight loss and female sexual dysfunction (“FSD”).
  • the combination of bupropion and trazodone unexpectedly treats and improves overweight, obesity or weight loss and HSDD. [0079] In some embodiments, the combination of bupropion and trazodone unexpectedly treats and improves both overweight, obesity or weight loss and female sexual arousal disorder (“FSAD”). [0080] In some embodiments, the combination of bupropion and trazodone unexpectedly treats and improves both overweight, obesity or weight loss and female orgasmic disorder (“FOD”). [0081] In some embodiments, the combination of bupropion and trazodone unexpectedly treats and improves both overweight, obesity or weight loss and female sexual interest/arousal disorder (“FSIAD”).
  • the combination of bupropion and trazodone unexpectedly treats and improves both overweight, obesity or weight loss and male sexual dysfunction (“MSD”).
  • MSD breast milk
  • the combination of bupropion and trazodone unexpectedly treats and improves both overweight, obesity or weight loss and erectile dysfunction (“ED”), Peyronie’s disease (“PD”), premature ejaculation (“PE”), male hypoactive sexual desire disorder (“MHSDD”), delayed ejaculation, decreased libido, and/or dry orgasm
  • the combination of bupropion and trazodone unexpectedly (1) induces weight loss in obese or overweight subjects or subjects desiring to lose weight, and (2) improves sexual disorder or dysfunction (SD), e.g., improves the Attorney Docket No.49848-4030PCT symptoms of SD, e.g., FSD, MSD, HSDD, FSAD, FOD, FSIAD, ED, PD,
  • the combination of bupropion and trazodone unexpectedly treats and induces and/or maintains weight loss, improves HSDD symptoms and improves a state, condition, or sense of poor or low or lack of subjective well-being, self- esteem, and/or self-confidence. [0086] , [0087] In some embodiments, the combination of bupropion and trazodone unexpectedly treats and induces and/or maintains weight loss, improves FSAD symptoms and improves a state, condition, or sense of poor or low or lack of subjective well-being, self-esteem, and/or self-confidence.
  • the combination of bupropion and trazodone unexpectedly treats and induces and/or maintains weight loss, improves FOD symptoms and improves a state, condition, or sense of poor or low or lack of subjective well-being, self-esteem, and/or self-confidence.
  • the combination of bupropion and trazodone unexpectedly treats and induces and/or maintains weight loss, improves MSD symptoms and improves a state, condition, or sense of poor or low or lack of subjective well-being, self-esteem, and/or self-confidence.
  • the combination of bupropion and trazodone unexpectedly treats and induces and/or maintains weight loss, improves SD symptoms and improves a state, condition, or sense of poor or low or lack of subjective well-being, self-esteem, and/or self-confidence.
  • the combination is believed to restore the balance of the three neurotransmitters that are known to regulate sexual inhibition and sexual excitation, subjective well-being, self-esteem, and/or self-confidence and appetite, i.e., dopamine, serotonin and norepinephrine and, in so doing, induces weight loss, increases sexual desire and sexual function, and improves subjective well-being, self-esteem, and/or self- confidence in treated subjects.
  • the combination is believed to maximize efficacy while balancing and neutralizing any side effects to minimize the risk of adverse or treatment-limiting events during treatment.
  • subjective well-being, self-esteem, and/or self-confidence may improve because of improvements in weight loss and/or weight loss management, improvements in self- appearance, improvements in symptoms associated with SD, improvements in sleep and/or improvements in energy.
  • improvements in weight loss and/or weight loss management improvements in self- appearance, improvements in symptoms associated with SD, improvements in sleep and/or improvements in energy.
  • improvements in symptoms associated with SD improvements in sleep and/or improvements in energy.
  • as the subjects' subjective well-being and/or self-confidence improve it in turn may enhance their self-esteem.
  • trazodone is used in the form of a pharmaceutically acceptable salt of acid addition.
  • One preferred form is the hydrochloride form obtained by treatment of the free base with hydrochloric acid. See, for example, U.S. Patent No.
  • Trazodone may be in immediate release (“IR”), extended release (“ER”) and sustained release (“SR”) forms.
  • IR immediate release
  • ER extended release
  • SR sustained release
  • the trazodone ER and trazodone SR forms are considered modified release or delayed release forms of trazodone.
  • bupropion is used in the form of a pharmaceutically acceptable salt of acid addition.
  • hydrochloride form obtained by treatment of the free base with hydrochloric acid.
  • hydrobromide form is the hydrobromide form.
  • Bupropion Hydrobromide is the hydrobromide salt of an aminoketone.
  • Bupropion hydrochloride may be in immediate release (IR), sustained release (SR), or extended release (XL) forms.
  • Bupropion SR and bupropion XL are considered to be modified release or delayed release forms of bupropion. See, for example, Bupropion, Medication Fact Sheet, American Association of Psychiatric Pharmacists (aapp.org), National Alliance on Mental Illness (NAMI), available online at https://www.nami.org/NAMI/media/NAMI-Media/Research/Bupropion.pdf.
  • the invention provides compositions and methods of treating an obese or overweight subject suffering from or susceptible to SD or symptoms thereof, e.g., FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, and low or poor or lack of a subjective state of well-being, self-esteem, and/or self-confidence comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition delineated herein.
  • the invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising a 5-HT2A antagonist, e.g., trazodone, a norepinephrine-dopamine reuptake inhibitor, e.g., bupropion, and a pharmaceutically acceptable carrier.
  • a 5-HT2A antagonist e.g., trazodone
  • a norepinephrine-dopamine reuptake inhibitor e.g., bupropion
  • a pharmaceutically acceptable carrier e.g., a pharmaceutically acceptable carrier.
  • the composition is both a 5-HT2A antagonist and a 5-HT1A receptor agonist.
  • the pharmaceutical composition comprises bupropion or a pharmaceutically acceptable salt thereof, and trazodone or a pharmaceutically acceptable salt thereof.
  • the pharmaceutical composition comprises trazodone or a pharmaceutically acceptable salt thereof in a dosage range of 25-450 mg and bupropion or a pharmaceutically acceptable salt thereof in a dosage range of 200-
  • composition is that comprising trazodone or a pharmaceutically acceptable salt thereof in a dosage range of 25-450 mg and bupropion or a pharmaceutically acceptable salt thereof in a dosage range of 25-450 mg.
  • methods of providing obesity or weight loss therapy particularly for patients who are obese or in need of weight loss and suffering from sexual inhibition.
  • methods of providing obesity or weight loss therapy particularly for patients who are obese or in need of weight loss and suffering Attorney Docket No.49848-4030PCT from low or poor or lack of a state of subjective well-being, self-esteem, and/or self- confidence.
  • the methods unexpectedly provide the same amount of weight loss combination drug dosages for obese patients who are suffering from lack of sexual desire and/or sexual function or low or poor or a lack of a subjective state of well-being, self-esteem, and/or self-confidence as in obese patients who are not suffering from a lack of sexual desire and/or sexual function or low or poor or lack of a subjective state of well-being, self-esteem, and/or self-confidence.
  • the dosages of bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof unexpectedly treat both obesity and lack of sexual desire and/or sexual function, and/or a low or poor or lack of a subjective state of well-being self-esteem, and/or self-confidence.
  • the methods unexpectedly provide the same amount of weight loss combination drug dosages for overweight patients who are suffering from a lack of sexual desire and/or sexual function or a low or poor or lack of a subjective state of well-being, self-esteem, and/or self-confidence swings as in overweight patients who are not suffering from a lack of sexual desire and sexual function or a low or poor or lack of a subjective state of well-being, self-esteem, and/or self- confidence swings.
  • the dosages of bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof unexpectedly treat both overweight and a lack of sexual desire and/or sexual function, and/or a subjective state of low or poor or lack of well-being, self-esteem, and/or self-confidence.
  • the dosages of bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof unexpectedly treat obesity, SD and/or a subjective state of low or poor or lack of well- being, self-esteem, and/or self-confidence.
  • the dosages of bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof unexpectedly treat overweight, SD and/or a subjective state of low or poor or lack of well- being, self-esteem, and/or self-confidence.
  • the dosages of bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof unexpectedly treat undesired weight, SD and/or a subjective state of low or poor or lack of well-being, self-esteem, and/or self-confidence.
  • the dosages of bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof unexpectedly treat weight loss maintenance, SD and/or a subjective state of low or poor or lack of well-being, self-esteem, and/or self-confidence.
  • a method for providing weight loss therapy to a patient comprising: identifying a patient suffering from obesity, being overweight or carrying undesired weight, and reducing weight of the patient in need of weight loss by administering to the patient the combination of bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the trazodone or a pharmaceutically acceptable salt thereof is in an amount effective to enhance the weight loss activity of the bupropion or a pharmaceutically acceptable salt thereof.
  • a method for providing weight loss therapy to a patient comprising: identifying a patient suffering from obesity, being overweight or carrying undesired weight, and reducing weight of the patient in need of weight loss by administering to the patient the combination of bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the bupropion or a pharmaceutically acceptable salt thereof is in an Attorney Docket No.49848-4030PCT amount effective to enhance the weight loss activity of the trazodone or a pharmaceutically acceptable salt thereof.
  • a method for providing weight loss therapy to a patient comprising: identifying a patient suffering from obesity, being overweight or carrying undesired weight, and reducing weight of the patient in need of weight loss by administering to the patient the combination of bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the trazodone or a pharmaceutically acceptable salt thereof and the bupropion or a pharmaceutically acceptable salt thereof are each in an amount effective to enhance the weight loss activity of one another.
  • a method for providing weight loss therapy to a patient comprising: identifying a patient suffering from SD, such as FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, wherein the patient is also overweight, obese or carrying undesired weight; and reducing weight of the patient in need of SD, e.g., FSD, HSDD, FSAD, FOD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, and weight loss treatment by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the trazodone or a pharmaceutically
  • a method for providing weight loss therapy to a patient comprising: identifying a patient suffering from a low or poor or lack of a state, condition, or sense of subjective well-being and/or self-esteem, wherein the patient is also overweight, obese or carrying undesired weight; and reducing weight of the patient in need of subjective well-being, self-esteem, and/or self-confidence and weight loss treatment by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the trazodone or a pharmaceutically acceptable salt thereof is in an amount effective to enhance the weight loss activity of the bupropion or a pharmaceutically acceptable salt thereof, the bupropion or a pharmaceutically acceptable salt thereof is in an amount effective to enhance the weight loss activity or effect of the trazodone or a pharmaceutically acceptable salt thereof, or the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are
  • the method further comprises adjusting the dosage of the bupropion or a pharmaceutically acceptable salt thereof, the trazodone or a pharmaceutically acceptable salt thereof, or both as needed to treat the patient's overweight, obesity or undesired weight. In certain embodiments, the method further comprises adjusting the dosage of the bupropion or a pharmaceutically acceptable salt thereof, the trazodone or a pharmaceutically acceptable salt thereof, or both as needed Attorney Docket No.49848-4030PCT to treat the patient's sexual inhibition.
  • the method further comprises adjusting the dosage of the trazodone or pharmaceutically acceptable salt thereof, the bupropion or pharmaceutically acceptable salt thereof, or both as needed to treat the patient's lack of sexual desire, sexual generies and/or sexual function. In certain embodiments, the method further comprises adjusting the dosage of the bupropion or a pharmaceutically acceptable salt thereof, the trazodone or a pharmaceutically acceptable salt thereof, or both as needed to treat the patient's SD.
  • the method further comprises adjusting the dosage of the bupropion or a pharmaceutically acceptable salt thereof, the trazodone or a pharmaceutically acceptable salt thereof, or both as needed to treat the patient's low or poor or lack of a subjective state of well-being, self-esteem, and/or self-confidence.
  • the patient is a woman.
  • the patient is a man.
  • the method further comprises administering the bupropion or a pharmaceutically acceptable salt thereof and bupropion trazodone or a pharmaceutically acceptable salt thereof with food.
  • At least one of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof is in a modified release delayed release formulation.
  • the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are in a modified release or delayed release formulation.
  • the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are in the same pharmaceutical composition.
  • the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are in separate pharmaceutical compositions.
  • the weight-loss inducing combination is administered once per day or more than once per day. In certain embodiments, the weight-loss inducing combination is administered acutely or chronically such as for a period of at least 3 months or longer. In certain embodiments, the weight-loss inducing combination is administered for a chronic period of at least 4 or 5 months.
  • the weight-loss inducing combination is administered for a chronic period of at least 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, 24 months or longer, or however long to accomplish the designated treatment objectives and/or weight loss management objectives in accordance with the present invention.
  • the weight-loss inducing combination is administered once per day or more than once per day as monotherapy.
  • the weight-loss inducing combination is administered once per day or more than once per day in combination with other weight loss therapies, such as in combination with the GLP-1 drugs.
  • the weight-loss inducing combination is administered once per day or more than once per day following the discontinuation of other weight loss medications, such as the discontinuation of the GLP-1 drugs, to maintain weight loss. [00119] In certain embodiments, the weight-loss inducing combination is administered once per day or more than once per day to maintain weight loss. [00120] In certain embodiments, the bupropion or a pharmaceutically acceptable salt thereof is administered prior or subsequent to the trazodone or a pharmaceutically acceptable salt thereof. In certain embodiments, the bupropion or a pharmaceutically acceptable salt thereof is administered in the morning and the trazodone or a Attorney Docket No.49848-4030PCT pharmaceutically acceptable salt thereof is administered at night.
  • the bupropion or a pharmaceutically acceptable salt thereof is administered twice daily, once in the morning and once at night, and the trazodone or a pharmaceutically acceptable salt thereof is administered once daily at night.
  • the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are co- administered or administered together once per day.
  • the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are both in sustained release form.
  • the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are in a single oral dosage form.
  • the single oral dosage form further comprises a pharmaceutically acceptable excipient, diluent, or carrier.
  • the single oral dosage form is a modified release or delayed release oral dosage form.
  • the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are each in sustained release form within the single oral dosage form.
  • a method for providing weight loss therapy to a patient comprising: identifying a patient who is obese, overweight or carrying undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is in the range of about 326 mg to about 374 mg per day, wherein the amount of the trazodone or a pharmaceutically acceptable salt thereof is in the range of from about 124 mg to about 147 mg per day, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a Attorney Docket No.49848-4030PCT pharmaceutically acceptable salt thereof are (i) in a single modified release or delayed release formulation, (ii) each in their own separate modified release or delayed release dosage forms, or (iii) each are in their own separate modified release or delayed release formulations in
  • a method for providing weight loss therapy to a patient comprising: identifying a patient who is obese, overweight or carrying undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is in the range of about 366 mg to about 374 mg per day, wherein the amount of the trazodone or a pharmaceutically acceptable salt thereof is in the range of from about 139 mg to about 147 mg per day, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single modified release or delayed release formulation, (ii) each in their own separate modified release or delayed release dosage forms, or (iii) each are in their own separate modified release or delayed release formulations in in a single dosage form.
  • a method for providing weight loss therapy to a patient comprising: identifying a patient who is obese, overweight or carrying undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is about 369.5 mg per day, wherein the amount of the trazodone or a pharmaceutically acceptable salt thereof is about 143.5 mg per day, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single modified release or delayed release formulation, (ii) each in their own separate modified release or delayed release dosage forms, or (iii) each are in their own separate modified release or delayed release formulations in in a single dosage form.
  • a method for providing weight loss therapy to a patient comprising: identifying a patient who is obese, overweight or carrying undesired weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is in the range of about 326 mg to about 334 mg per day, wherein the amount of the trazodone or a pharmaceutically acceptable salt thereof is in the range of from about 124 mg to about 132 mg per day, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single modified release or delayed release formulation, (ii) each in their own separate modified release or delayed release dosage forms, or (iii) each are in their own separate modified release or delayed release formulations in in in in in in in
  • a method for providing weight loss therapy to a patient comprising: identifying a patient who is obese, overweight or carrying undesired weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is about 329.5 mg per day, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is about 128.5 mg per day, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single modified release or delayed release formulation, (ii) each in their own separate modified release or delayed release dosage forms, or (iii) each are in their own separate modified release or delayed release formulations in in a single dosage form.
  • the preferred amount of the bupropion or pharmaceutically acceptable salt thereof when treating a patient who is obese, is in the range of about 366 mg to about 374 mg per day, and the preferred amount of the trazodone or a Attorney Docket No.49848-4030PCT pharmaceutically acceptable salt thereof is in the range of from about 139 mg to about 147 mg per day. [00130] In some embodiments, when treating a patient who is obese, the preferred amount of the bupropion or pharmaceutically acceptable salt thereof is about 369.5 mg per day and the preferred amount of the trazodone or a pharmaceutically acceptable salt thereof is about 143.5 mg per day.
  • the preferred amount of the bupropion or pharmaceutically acceptable salt thereof when treating a patient who is not obese, but who is overweight or has undesired or unwanted weight, is in the range of about 326 mg to about 334 mg per day, wherein the preferred amount of the trazodone or a pharmaceutically acceptable salt thereof is in the range of from about 124 mg to about 132 mg per day.
  • the preferred amount of the bupropion or pharmaceutically acceptable salt thereof when treating a patient who is not obese, but who is overweight or has undesired or unwanted weight, is about 329.5 mg per day and the preferred amount of the trazodone or a pharmaceutically acceptable salt thereof is about 128.5 mg per day.
  • a method for providing weight loss therapy to a patient comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, and/or having low or poor or lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence, wherein the patient is also obese, overweight or carrying undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is in the range of about 326 mg to about 374 mg per day, wherein the amount of the trazodone or Attorney Docket No.49848-4030PCT a pharmaceutically
  • a method for providing weight loss therapy to a patient comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, and/or having low or poor or a lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence, wherein the patient is also obese, overweight or carrying undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is in the range of about 366 mg to about 374 mg per day, wherein the amount of the trazodone or a pharmaceutically acceptable salt thereof is in the range of from about
  • a method for providing weight loss therapy to a patient comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, and/or having low or poor or lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence, wherein the patient is also obese, overweight or carrying undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically Attorney Docket No.49848-4030PCT acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is about 369.5 mg per day, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is about 143.5 mg per day, and wherein
  • SD e.g., FSD
  • a method for providing weight loss therapy to a patient comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, and/or having low or poor or a lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence, wherein the patient is also obese, overweight or carrying undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is in the range of about 326 mg to about 334 mg per day, wherein the amount of the trazodone or a pharmaceutically acceptable salt thereof is in the range of from about
  • a method for providing weight loss therapy to a patient comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, and/or having low or poor or lack of a Attorney Docket No.49848-4030PCT subjective state or sense of well-being, self-esteem, and/or self-confidence, wherein the patient is also obese, overweight or carrying undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is about 329.5 mg per day, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is about 128.5 mg per day, and wherein
  • a method for providing weight loss therapy to a patient comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, and/or having low or poor or lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence, wherein the patient is also obese, overweight or carrying undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the amount of the bupropion or pharmaceutically acceptable salt thereof is in the range of about 200 mg to about 400 mg per day, wherein the amount of the trazodone or a pharmaceutically acceptable salt thereof is in the range of from about 50 mg to about
  • SD e.g., FSD,
  • a method for providing weight loss therapy to a patient comprising: identifying a patient suffering from obesity or being overweight or having undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 250 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning and wherein about 100 mg of bupropion or a pharmaceutically acceptable salt thereof is administered at night or at bedtime, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 75 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single modified release or delayed release formulation,
  • a method for providing weight loss therapy to a patient comprising: identifying a patient suffering from obesity or being overweight or having undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 150 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 75 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single modified release or delayed release formulation, (ii) each in their own separate modified release or delayed release dosage forms, or (iii) each are in their own separate modified release or delayed release formulations in in in in in in in
  • a method for providing weight loss therapy to a patient comprising: identifying a patient suffering from obesity or being overweight or having undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 250 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning and wherein about 100 mg of bupropion or a pharmaceutically acceptable salt thereof is administered at night or at bedtime, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 150 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single modified release or delayed release formulation,
  • a method for providing weight loss therapy to a patient comprising: identifying a patient suffering from obesity or being overweight or having undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 150 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 150 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single modified release or delayed release formulation, (ii) each in their own separate modified release or delayed release dosage forms, or (iii) each are in their own separate modified release or delayed release formulations in in in in in in in
  • a method for providing weight loss therapy to a patient comprising: identifying a patient suffering from obesity or being overweight or having undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 300 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning and wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered at night or at bedtime, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 75 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single modified release or delayed release formulation,
  • a method for providing weight loss therapy to a patient comprising: identifying a patient suffering from obesity or being overweight or having undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 300 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning and wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered at night or at bedtime, and wherein the trazodone or a pharmaceutically acceptable salt thereof is administered at night or at bedtime in an amount of about 150 mg, and wherein each of the bupropion or a pharmaceutically acceptable salt thereof and the trazodone or a pharmaceutically acceptable salt thereof are (i) in a single modified release or delayed release formulation, (ii) each in their own separate modified release or delayed
  • a method for providing weight loss therapy to a patient comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, and/or having low or poor or lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence, wherein the patient is also obese, overweight or carrying undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 250 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning and wherein about
  • a method for providing weight loss therapy to a patient comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, and/or having low or poor or lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence, wherein the patient is also obese, overweight or carrying undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 250 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable Attorney Docket No.49848-4030PCT salt thereof is administered in the morning and wherein about
  • a method for providing weight loss therapy to a patient comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, and/or having low or poor or lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence, wherein the patient is also obese, overweight or carrying undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 150 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning, and wherein the trazodone or a pharmaceutically acceptable
  • a method for providing weight loss therapy to a patient comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, Attorney Docket No.49848-4030PCT decreased libido, dry orgasm, and the like, and/or having low or poor or lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence, wherein the patient is also obese, overweight or carrying undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 150 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning, and wherein
  • a method for providing weight loss therapy to a patient comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, and/or having low or poor or lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence, wherein the patient is also obese, overweight or carrying undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 300 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning and wherein about 150 mg of bupropion or a pharmaceutically acceptable salt
  • a method for providing weight loss therapy to a patient comprising: identifying a patient suffering from SD, e.g., FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, and/or having low or poor or lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence, wherein the patient is also obese, overweight or carrying undesired or unwanted weight; and reducing weight of the patient by administering to the patient bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof, wherein the daily amount of the bupropion or a pharmaceutically acceptable salt thereof is about 300 mg, wherein about 150 mg of bupropion or a pharmaceutically acceptable salt thereof is administered in the morning and wherein about 150 mg of bupropion or a pharmaceutically acceptable salt
  • the method further comprises regulating and/or improving the patient’s low or poor or lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence by increasing and/or balancing the norepinephrine and dopamine hormone levels in the patient’s brain to shift or improve the patient’s subjective state or sense of well-being, self-esteem, and/or self-confidence.
  • a method for selecting a weight loss therapy from among available weight loss therapies comprising: evaluating a patient to assess whether the patient is simultaneously in need of weight loss therapy and depression therapy and/or or a subjective state or sense well-being, self-esteem, and/or self-confidence therapy; and if so, providing to the patient an effective weight-loss- inducing and antidepressant and/or a subjective state or sense of well-being, self-esteem, and/or self-confidence improvement combination of bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof as active ingredients.
  • the method further comprises providing printed information to the patient indicating that the combination promotes weight loss and reduces symptoms of depression and/or low or poor or lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence.
  • the patient has been diagnosed as suffering from major depressive disorder using the Montgomery-Asberg Depression Rating Scale (MADRS).
  • MADRS Montgomery-Asberg Depression Rating Scale
  • the patient has been diagnosed as suffering from major depressive disorder using the Inventory of Depressive Symptomatology.
  • the patient is not suffering from bipolar disorder.
  • the patient is suffering from low or poor or lack of a subjective state or sense of well-being, self-esteem, and/or self- confidence.
  • the patient is suffering from a sexual disorder.
  • the patient is suffering from obesity or being overweight.
  • the patient has a body mass index of 25 kg/m 2 or above. In certain embodiments, the patient has a body mass index of 30 kg/m 2 or above. In certain embodiments, the patient is overweight. In certain embodiments, the patient is obese. In certain embodiments, the patient has a body mass index below 30 kg/m 2 . In certain embodiments, the patient has a body mass index below 25 kg/m 2 . In certain embodiments, the patient is not obese. In certain embodiments, the patient is overweight, not obese. In certain embodiments, the patient is neither overweight nor obese, but desires to lose weight or carries undesired or unwanted weight.
  • a pharmaceutical composition comprises bupropion or a pharmaceutically acceptable salt thereof in a dosage range of about 200 to about 450 mg; comprises bupropion or a pharmaceutically acceptable salt thereof in a dosage range of about 225 to about 300 mg; or comprises bupropion or a pharmaceutically acceptable salt thereof in a dosage range of about 200 to about 275 mg; comprises bupropion or a pharmaceutically acceptable salt thereof in a dosage range of about 100 to about 450 mg; comprises bupropion or a pharmaceutically acceptable salt thereof in a dosage range of about 100 to about 275 mg; comprises bupropion or a pharmaceutically acceptable salt thereof in a dosage range of about 25 to about 275 mg; comprises bupropion or a pharmaceutically acceptable salt thereof in a dosage range of about XX to about YY mg, wherein XX is any integer between and including 5 and 400 and YY is any integer between and including 50 and 450.
  • a pharmaceutical composition comprises trazodone or a pharmaceutically acceptable salt thereof in a dosage range of about 25 to about 450 mg; comprises trazodone or a pharmaceutically acceptable salt thereof in a dosage range of about 75 to about 150 mg; or comprises trazodone or a pharmaceutically acceptable salt thereof in a dosage range of about 50 to about 100 mg; comprising trazodone or a pharmaceutically acceptable salt thereof in a dosage range of about XX to about YY mg, wherein XX is an integer between and including 25 and 400 and YY is an integer between and including 50 and 450.
  • the present invention provides a method of treating an obese or overweight subject or a subject carrying undesirable or unwanted weight who is suffering from or susceptible to SD comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising a 5-HT2A antagonist, a norepinephrine-dopamine reuptake inhibitor, and a pharmaceutically acceptable carrier.
  • a composition comprising a 5-HT2A antagonist, a norepinephrine-dopamine reuptake inhibitor, and a pharmaceutically acceptable carrier.
  • one compound is both a 5-HT2A antagonist and a 5-HT1A receptor agonist, e.g., trazodone or a pharmaceutically acceptable salt thereof.
  • the norepinephrine-dopamine reuptake inhibitor is also an alpha-adrenergic blocker, e.g., bupropion or a pharmaceutically acceptable salt thereof.
  • the SD is Attorney Docket No.49848-4030PCT FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like.
  • the present invention provides a method of treating an obese or overweight subject or a subject carrying undesirable or unwanted weight who is suffering from or susceptible to low or poor or lack of a subjective state or sense of well- being, self-esteem, and/or self-confidence comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising a 5-HT2A antagonist, a norepinephrine-dopamine reuptake inhibitor, and a pharmaceutically acceptable carrier.
  • one compound is both a 5-HT2A antagonist and a 5- HT1A receptor agonist, e.g., trazodone or a pharmaceutically acceptable salt thereof.
  • the norepinephrine-dopamine reuptake inhibitor is also an alpha- adrenergic blocker, e.g., bupropion or a pharmaceutically acceptable salt thereof.
  • the present invention provides a method of treating an obese or overweight subject or a subject carrying undesirable or unwanted weight who is suffering from or susceptible to a SD and low or poor or lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising a 5-HT2A antagonist, a norepinephrine-dopamine reuptake inhibitor, and a pharmaceutically acceptable carrier.
  • one compound is both a 5-HT2A antagonist and a 5- HT1A receptor agonist, e.g., trazodone or a pharmaceutically acceptable salt thereof.
  • the norepinephrine-dopamine reuptake inhibitor is also an alpha- adrenergic blocker, e.g., bupropion or a pharmaceutically acceptable salt thereof.
  • the SD is FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like.
  • the norepinephrine-dopamine reuptake inhibitor is also an alpha- adrenergic blocker, e.g., bupropion or a pharmaceutically acceptable salt thereof.
  • the SD is SD, FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like.
  • the present invention provides a method of treating an obese subject who is suffering from or susceptible to a sexual disease or disorder SD and low or poor or lack of a subjective state or sense of well-being, self-esteem, and/or self- confidence comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising a 5-HT2A antagonist, a norepinephrine- dopamine reuptake inhibitor, and a pharmaceutically acceptable carrier.
  • one compound is both a 5-HT2A antagonist and a 5-HT1A receptor agonist, e.g., trazodone or a pharmaceutically acceptable salt thereof.
  • the norepinephrine- dopamine reuptake inhibitor is also an alpha-adrenergic blocker, e.g., bupropion or a pharmaceutically acceptable salt thereof.
  • the SD is FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like.
  • the present invention provides a method of treating an overweight subject or a subject carrying undesirable or unwanted weight who is suffering from or susceptible to SD comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising a 5-HT2A antagonist, a norepinephrine-dopamine reuptake inhibitor, and a pharmaceutically acceptable carrier.
  • a composition comprising a 5-HT2A antagonist, a norepinephrine-dopamine reuptake inhibitor, and a pharmaceutically acceptable carrier.
  • one compound is both a 5-HT2A antagonist and a 5-HT1A receptor agonist, e.g., trazodone or a pharmaceutically acceptable salt thereof.
  • the norepinephrine-dopamine reuptake inhibitor is also an alpha-adrenergic blocker, e.g., bupropion or a pharmaceutically acceptable salt thereof.
  • the SD is FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like.
  • the present invention provides a method of treating an overweight subject or a subject carrying undesirable or unwanted weight who is suffering from or susceptible to a sexual disease or disorder SD and low or poor or lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising a 5-HT2A antagonist, a norepinephrine-dopamine reuptake inhibitor, and a pharmaceutically acceptable carrier.
  • one compound is both a 5-HT2A antagonist and a 5-HT1A receptor agonist, e.g., trazodone or a pharmaceutically acceptable salt thereof.
  • the norepinephrine- dopamine reuptake inhibitor is also an alpha-adrenergic blocker, e.g., bupropion or a pharmaceutically acceptable salt thereof.
  • the SD is FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like.
  • the SD includes hyposexual desire disorder (HSDD), female sexual disorder (FSD), is female sexual arousal disorder (FSAD), female orgasmic disorder (FOD) and/or female sexual interest/arousal disorder (FSIAD).
  • Another aspect is a method of treating a disease, disorder or symptom thereof described in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) in an obese or overweight subject or a subject carrying undesirable or unwanted weight, comprising administering to the subject the combination of bupropion, or a pharmaceutically acceptable salt thereof, and trazodone, or a pharmaceutically Attorney Docket No.49848-4030PCT acceptable salt thereof, each in effective amounts to reduce weight and effectively treat such disease, disorder or symptom thereof.
  • DSM-IV Diagnostic and Statistical Manual of Mental Disorders
  • Another aspect is a method of treating erectile dysfunction (ED) in an obese or overweight subject or a subject carrying undesirable or unwanted weight comprising administering to the subject the combination of bupropion, or a pharmaceutically acceptable salt thereof, and trazodone, or a pharmaceutically acceptable salt thereof, each in effective amounts to reduce weight and effectively treat ED.
  • Another aspect is a method of treating HSDD in an obese or overweight male or female subject or a male or female subject who is carrying undesirable or unwanted weight comprising administering to the male or female subject the combination of bupropion, or a pharmaceutically acceptable salt thereof, and trazodone, or a pharmaceutically acceptable salt thereof, each in effective amounts to reduce weight and effectively treat the HSDD and/or improve symptoms thereof.
  • Another aspect is an extended release composition of a 5-HT2A antagonist and a 5-HT1A receptor agonist, e.g., trazodone or a pharmaceutically acceptable salt thereof an alpha-adrenergic blocker, e.g., bupropion or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
  • a sustained release composition a 5-HT2A antagonist and a 5-HT1A receptor agonist, e.g., trazodone or a pharmaceutically acceptable salt thereof an alpha-adrenergic blocker, e.g., bupropion or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
  • compositions are administered orally; wherein the composition is administered topically; wherein the subject is diagnosed and being treated for depression and/or low or poor or lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence; wherein the subject is not undergoing treatment for depression and/or low or poor or lack of a subjective state or sense of well- being, self-esteem, and/or self-confidence; wherein the subject is concurrently prescribed or administered an additional therapeutic agent; or wherein the subject is concurrently not prescribed or administered an additional therapeutic agent; wherein the subject is concurrently prescribed or administered an additional weight-loss agent; or wherein the subject is concurrently not prescribed or administered an additional weight-loss agent.
  • the composition is that comprising bupropion or a pharmaceutically acceptable salt thereof in a dosage range of about 100 to about 450 mg qd; comprising bupropion or a pharmaceutically acceptable salt thereof in a dosage range of about 200 to about 450 mg qd; comprising bupropion or a pharmaceutically acceptable salt thereof in a dosage range of about 100 to about 300 mg qd; comprising bupropion or a pharmaceutically acceptable salt thereof in a dosage range of about 225 to about 300 mg qd; comprising bupropion or a pharmaceutically acceptable salt thereof in a dosage range of about 100 to about 275 mg qd; comprising bupropion or a pharmaceutically acceptable salt thereof in a dosage range of about 200 to about 275 mg qd; or comprising bupropion or a pharmaceutically acceptable salt thereof in a dosage range of about XX to about YY mg qd, wherein XX is an integer between and includes 5 and 400 and YY is an integer between and includes 50 and 450.
  • a pharmaceutical composition comprises trazodone or a pharmaceutically acceptable salt thereof in a dosage range of about 25 to about 450 mg qd; comprises trazodone or a pharmaceutically acceptable salt thereof in a dosage range of about 75 to about 150 mg qd; or comprises trazodone or a pharmaceutically acceptable salt thereof in a dosage range of about 50 to about 100 mg qd; comprises trazodone or a pharmaceutically acceptable salt thereof in a dosage range of about XX to about YY mg Attorney Docket No.49848-4030PCT qd, wherein XX is an integer between and including 25 and 400 and YY is an integer between and including 50 and 450.
  • a pharmaceutical composition comprises bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof; comprises bupropion or a pharmaceutically acceptable salt thereof in a dosage range of about 50 to about 450 mg and trazodone or a pharmaceutically acceptable salt thereof in a dosage range of about 25 to about 450 mg; comprises bupropion or a pharmaceutically acceptable salt thereof in a dosage range of about 200 to about 450 mg and trazodone or a pharmaceutically acceptable salt thereof in a dosage range of about 25 to about 450 mg; comprises bupropion or a pharmaceutically acceptable salt thereof in a dosage range of about 100 to about 300 mg qd and comprises trazodone or a pharmaceutically acceptable salt thereof in a dosage range of about 75 to about 150 mg qd; comprises bupropion or a pharmaceutically acceptable salt thereof in a dosage range of about 225 to about 300 mg qd and comprises trazodone or a pharmaceutically acceptable salt thereof in a dosage
  • the present invention provides a method of making a pharmaceutical composition comprising combining a 5-HT2A antagonist, a norepinephrine- dopamine reuptake inhibitor, and a pharmaceutically acceptable carrier. In one aspect, the present invention provides a method of making a pharmaceutical composition comprising combining a 5-HT1A receptor agonist, a 5-HT2A antagonist, and a pharmaceutically acceptable carrier. In one aspect, the present invention provides a method of making a pharmaceutical composition comprising combining a 5-HT1A receptor agonist, and a pharmaceutically acceptable carrier.
  • the present invention provides a Attorney Docket No.49848-4030PCT method of making a pharmaceutical composition comprising a 5-HT2A antagonist, and a pharmaceutically acceptable carrier.
  • the method of making a pharmaceutical composition comprises combining a 5-HT1A receptor agonist, a norepinephrine-dopamine reuptake inhibitor and a pharmaceutically acceptable carrier such that the pharmaceutical composition comprises a range of about 25 mg to about 450 mg of a 5-HT1A receptor agonist.
  • the method of making a pharmaceutical composition comprises combining a 5-HT2A antagonist and a pharmaceutically acceptable carrier such that the pharmaceutical composition comprises a range of about 25 mg to about 450 mg of a 5- HT2A antagonist and a norepinephrine-dopamine reuptake inhibitor.
  • the method comprises combining bupropion or a pharmaceutically acceptable salt thereof, trazodone or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
  • the present invention provides a kit comprising a pharmaceutical composition delineated herein and a label providing instructions for administration of the pharmaceutical composition to an obese or overweight subject or a subject carrying undesirable or unwanted weight for treating or ameliorating the subject’s obesity, overweightness or undesirable or unwanted weight and the subject’s SD or symptoms thereof.
  • the present invention provides a kit comprising a pharmaceutical composition delineated herein and a label providing instructions for administration of the pharmaceutical composition to an obese or overweight subject or a subject carrying undesirable or unwanted weight for treating or ameliorating the subject’s obesity, overweightness or undesirable or unwanted weight and the subject’s low or poor or lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence or symptoms thereof.
  • the present invention provides a kit comprising a pharmaceutical composition delineated herein and a label providing instructions for administration of the pharmaceutical composition to an obese or overweight subject or a subject carrying undesirable or unwanted weight for treating or ameliorating the subject’s obesity, overweightness or undesirable or unwanted weight and the subject’s SD or symptoms thereof and the subject’s low or poor or lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence or symptoms thereof.
  • the present invention provides a method of treating an obese or overweight subject or a subject with undesirable or unwanted weight with SD comprising administering to the subject a 5-HT1A receptor agonist, and a 5-HT2A antagonist and a norepinephrine-dopamine reuptake inhibitor.
  • the methods herein can further comprise those wherein the subject is identified as in need of such treatment, and those wherein the subject is treated upon administration of the combinations and/or pharmaceutical compositions herein.
  • the methods can include those wherein the subject has not previously been administered the combinations and/or pharmaceutical compositions herein, or wherein the subject has not previously been administered the combinations and/or pharmaceutical compositions herein at the stated dosage levels or treatment administration or co-administration regimens.
  • the invention provides a method of treating an obese or overweight subject or a subject carrying undesirable or unwanted weight comprising administering to the obese or overweight subject in need thereof a therapeutically effective amount of a composition comprising any one of a 5-HT2A antagonist and a 5-HT1A receptor agonist, e.g., trazodone or a pharmaceutically acceptable salt thereof, a norepinephrine-dopamine reuptake inhibitor, e.g., bupropion or a pharmaceutically acceptable salt thereof, an endocrine active agent, and a pharmaceutically acceptable carrier to treat the subject for obesity, being overweight or carrying undesirable or unwanted weight.
  • a composition comprising any one of a 5-HT2A antagonist and a 5-HT1A receptor agonist, e.g., trazodone or a pharmaceutically acceptable salt thereof, a norepinephrine-dopamine reuptake inhibitor, e.g., bupropion or a pharmaceutically acceptable salt thereof, an endocrine active agent, and
  • the invention provides a method of treating an obese or overweight subject or a subject carrying undesirable or unwanted weight who is suffering from or susceptible to a SD and low or poor or lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence comprising administering to the subject in need thereof a therapeutically effective amount of a composition comprising any one of a 5-HT2A antagonist and a 5-HT1A receptor agonist, e.g., trazodone or a pharmaceutically acceptable salt thereof, a norepinephrine-dopamine reuptake inhibitor, e.g., bupropion or a pharmaceutically acceptable salt thereof, an endocrine active agent, and a pharmaceutically acceptable carrier to treat the subject for obesity, for being overweight, for carrying undesirable or unwanted weight, SD and/or low or poor or lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence.
  • a composition comprising any one of a 5-HT2A antagonist and a 5-HT1A receptor agonist
  • the invention provides a method of treating obesity, overweightness, or undesirable or unwanted weight in a subject comprising administering to the subject a therapeutically effective amount of any one of a 5-HT2A antagonist, a norepinephrine-dopamine reuptake inhibitor, a 5-HT1A receptor agonist, an endocrine active agent, or any combination thereof.
  • the invention provides a method of treating obesity, overweightness, or undesirable or unwanted weight and a SD in a subject comprising administering to the subject a therapeutically effective amount of any one of a 5-HT2A antagonist, a norepinephrine-dopamine reuptake inhibitor, a 5-HT1A receptor agonist, an endocrine active agent, or any combination thereof.
  • the present invention provides a method of treating obesity, overweightness, or undesirable or unwanted weight and low or poor or lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence in a subject comprising administering to the subject a therapeutically effective amount of any one of a 5-HT2A antagonist, a norepinephrine-dopamine reuptake inhibitor, a 5-HT1A receptor agonist, an endocrine active agent, or any combination thereof.
  • the present invention provides a method of treating obesity, overweightness, or undesirable or unwanted weight, a SD and low or poor or lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence in a subject comprising administering to the subject a therapeutically effective amount of any one of a 5-HT2A antagonist, a norepinephrine-dopamine reuptake inhibitor, a 5-HT1A receptor agonist, an endocrine active agent, or any combination thereof.
  • the endocrine agent is testosterone, which can be in an amount of a daily or weekly, bi-weekly or monthly dosage range of about 25 mg to about 1000 mg.
  • the subject is that wherein the subject is not being treated with a selective serotonin reuptake inhibitor (SSRI) agent.
  • SSRI selective serotonin reuptake inhibitor
  • the subject is that wherein the subject is being treated with a selective serotonin reuptake inhibitor (SSRI) agent.
  • the subject is that wherein the subject is identified as having selective serotonin reuptake inhibitor (SSRI) agent induced SD.
  • the subject is that wherein the subject is identified as having selective serotonin reuptake inhibitor (SSRI) agent induced FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like.
  • SSRI selective serotonin reuptake inhibitor
  • the subject is that wherein the subject is identified as having selective serotonin reuptake inhibitor (SSRI) agent induced low or poor or lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence.
  • the subject is that wherein the subject is being treated with a PDE-5 inhibitor compound (i.e., sildenafil, tadalafil, and the like), especially for but not limited to ED.
  • a PDE-5 inhibitor compound i.e., sildenafil, tadalafil, and the like
  • the subject is that wherein the subject is not concurrently being treated with a PDE-5 inhibitor compound, e.g., sildenafil, tadalafil, and the like.
  • the subject is that wherein the subject is being treated with an endocrine agent, e.g., testosterone.
  • the present invention is directed to novel and unique compositions comprising bupropion in an effective amount and trazodone in an effective amount for inducing weight loss, maintaining weight loss, and/or effectuating weight loss management, improving the subjective state or sense of well-being, self-esteem, and/or self-confidence, and increasing, enhancing and/or improving sexual desire and function in treated subjects in need of such treatment.
  • the present invention is directed to novel and unique compositions comprising bupropion in an effective amount and trazodone in an effective amount for inducing weight loss, maintaining weight loss, and/or effectuating weight loss management and increasing, enhancing and/or improving sexual desire, sexual fantasies and/or sexual function in treated subjects in need of such treatment.
  • the present invention is directed to novel and unique compositions comprising bupropion in an effective amount and trazodone in an effective amount for inducing weight loss, maintaining weight loss, and/or effectuating weight loss management and improving the subjective state or sense of well-being, self-esteem, and/or self-confidence in treated subjects in need of such treatment.
  • the present invention is directed to novel and unique compositions comprising bupropion in an effective amount and trazodone in an effective amount for inducing weight loss, maintaining weight loss, and/or effectuating weight loss management, increasing, enhancing and/or improving sexual desire, sexual fantasies and/or sexual function and improving the subjective state of a state or sense of well-being, self-esteem, and/or self-confidence in treated subjects in need of such treatment.
  • the present inventors have now discovered a therapeutic strategy that addresses obesity, weight loss, and weight loss maintenance in a subject.
  • the present inventors have also now discovered a therapeutic strategy that addresses obesity, weight loss, undesirable or unwanted weight, weight loss maintenance and one or more of the following SDs, namely, FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, and low or poor or a lack of a subjective state or sense of well-being, self-esteem, and/or self- confidence in a subject.
  • SDs namely, FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, and low or poor or a lack of a subjective state or sense of well-being, self-esteem, and/or self- confidence in a subject.
  • the present invention relates, at least in part, to the discovery that a combination of a 5-HT2A antagonist (which is optionally a 5-HT1A receptor agonist), a Attorney Docket No.49848-4030PCT norepinephrine-dopamine reuptake inhibitor, (and optionally an endocrine active agent) provides unexpected superior and synergistic results in addressing obesity, weight loss, undesirable or unwanted weight, weight loss maintenance, SD, and/or low or poor or a lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence in a subject.
  • a 5-HT2A antagonist which is optionally a 5-HT1A receptor agonist
  • a Attorney Docket No.49848-4030PCT norepinephrine-dopamine reuptake inhibitor (and optionally an endocrine active agent) provides unexpected superior and synergistic results in addressing obesity, weight loss, undesirable or unwanted weight, weight loss maintenance, SD, and/or low or poor or
  • the present invention relates, at least in part, to the discovery that the combination of a 5-HT2A antagonist (which is optionally a 5-HT1A receptor agonist), and norepinephrine-dopamine reuptake inhibitor, provides unexpected superior and synergistic results in addressing obesity, weight loss, and/or effectuating weight loss maintenance.
  • a 5-HT2A antagonist which is optionally a 5-HT1A receptor agonist
  • norepinephrine-dopamine reuptake inhibitor provides unexpected superior and synergistic results in addressing obesity, weight loss, and/or effectuating weight loss maintenance.
  • the present invention relates, at least in part, to the discovery that the combination of a 5-HT2A antagonist (which is optionally a 5-HT1A receptor agonist), and norepinephrine-dopamine reuptake inhibitor, provides unexpected superior and synergistic results in addressing obesity, weight loss, undesirable or unwanted weight, and/or weight loss maintenance and one or more of the following SDs, such as FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, and low or poor or a lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence in a subject.
  • SDs such as FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD
  • the present invention also provides novel and unique methods for treating subjects in need of treatment for obesity, weight loss, undesirable or unwanted weight, and/or weight loss maintenance, and one or more of the following FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, and/or poor or low or a lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence.
  • range(s), are inclusive of the recited endpoints and independently combinable, for example, the range of “from 2 grams to 10 grams” is inclusive of the endpoints, 2 grams and 10 grams, and all the intermediate numerical gram values therebetween, as if each intermediate numerical gram value therebetween has been individually set forth herein.
  • the term “about” can be used to include any numerical value that can vary without changing the basic function of that value. When used with a range, “about” also discloses the range defined by the absolute values of the two endpoints, e.g.
  • the term “substantially free of” or “substantially free” in terms of a specified component is used herein to mean that none of the specified component has been purposefully formulated into or is included in a composition or compound and/or is present only as a contaminant or in trace amounts. The total amount of all containments, by-products, and other material present in a composition or compound is in an amount less than 5%.
  • the term “more substantially free of” or “more substantially free” is used to represent that a composition or compound contains less than 3% of a specific component.
  • the term “essentially free of” or “essentially free” contains less than 2% of a specific component.
  • patient(s),” “subject(s),” or “individual(s)” or “person(s) are used interchangeably herein and refer to either a human or a non-human animal. These terms include any mammals, such as humans, primates, livestock animals, including bovines, porcine, etc., companion or domesticated animals, e.g., canines, felines, etc., rodents and laboratory animals, e.g., mice, rats, dogs, rabbits, monkeys, and the like, and wild and zoo animals, e.g., lions, tigers, bears, elephants, giraffes, etc. In a typical embodiment, the subject or patient is a human, male and female.
  • the term "subject” includes Attorney Docket No.49848-4030PCT animals which are capable of suffering from a sexual disorder or who could otherwise benefit from the administration of a compound or composition of the invention, such as human (male or female) and non-human animals (male or female).
  • Preferred humans include obese or overweight human patients.
  • Other preferred humans include obese or overweight human patients suffering from or prone to suffering from hypoactive sexual desire disorder or associated state or other sexual disorders or disease, as described herein.
  • a "Responder" means a sexual desire Responder, one who improves by 2 points on the standard scale from 2-10.
  • a sexual distress Responder is defined on the desire subscale of the Female Sexual Function Inventory; the subscale ranges from 2 (desire at very low or none and almost never or never) to 10 (desire at very high and almost always or always).
  • a "Remitter”, as used herein is one whose score is at least 5.
  • a sexual distress Responder is one who improves by one point on the standard scale from 0 to 4. The measure is the "bothered by low sexual desire" item of the Female Sexual Distress Scale - Revised, and it ranges from 4, always, to 0, never, and a Remitter is one whose score is no higher than 2, occasionally.
  • administering or “administration of” or “administered” or “administers,” as used herein, are used interchangeably and relate to administering a substance, a compound, a pharmaceutical composition, product, agent, or medical treatment to a patient to perform their intended function and that can be carried out using one of a variety of methods known to those skilled in the art.
  • the terms therefore include routes of introducing the compounds or compositions of the present invention to a subject to perform their intended function and carry out the objectives of the present invention.
  • a substance, compound, composition, product, agent, including the combination of the present invention, or medical treatment can be administered intravenously, arterially, intradermally, intramuscularly, intraperitoneally, subcutaneously, Attorney Docket No.49848-4030PCT ocularly, sublingually, orally (by ingestion), intranasally, including by inhalation, intraspinal, intracerebral, and transdermal by absorption, e.g., through a skin duct.
  • a substance, compound, composition, product, agent, including the combinations of the present invention, or medical treatment can also appropriately be introduced by rechargeable or biodegradable polymeric devices or other devices, e.g., patches and pumps, or formulations, which provide for the extended, slow, modified or controlled, sustained or delayed release of the substance, compound or agent.
  • Administration can also be performed, for example, once, a plurality of times, and/or over one or more extended periods.
  • the pharmaceutical preparations of the [present invention may be given by forms suitable for each administration route. For example, these preparations are administered in tablet, caplet or capsule form, by injection, inhalation, eye lotion, ointment, suppository, etc.
  • administration by injection, infusion or inhalation; topical by lotion or ointment; and rectal by suppositories.
  • Oral administration is preferred.
  • the injection can be bolus, auto-injected or self -injected, or can be continuous infusion.
  • the compound of the invention can be coated with or disposed of in a selected material to protect it from natural conditions which may detrimentally affect its ability to perform its intended function.
  • the compounds of the present invention can be administered alone, or in conjunction with either another agent as described above or with a pharmaceutically acceptable carrier, or both.
  • the compounds of the present invention can be administered prior to the administration of the other agent, simultaneously with the agent, or after the administration of the agent.
  • the compounds of the present invention can also be administered in a pro- drug form which is converted into its active metabolite, or more active metabolite in vivo.
  • co-administration refers to the act of administering or giving or taking two or more drugs or medical treatments together at a certain time, such as either (a) at the same or identical time, (b) at about the same time, (c) at substantially the same time, (d) at different times of the day, or (e) on different days of the week, month or year, depending upon the treatment regimen, dosage form and dosage strength of each drug being co-administered.
  • route(s) of medication and these above terms in this Attorney Docket No.49848-4030PCT ⁇ 222 refer to the route by which each drug or medical treatment is administered, given or taken, such as enteral, oral, sublingual, buccal, rectal, parenteral, intravenous, intramuscular, subcutaneous, topical, nasal and/or inhalation routes of medication and as described herein.
  • the pharmaceutical preparations may be given by forms suitable for each administration route. For example, these preparations are administered in tablet, caplet, capsule, or powder form, by injection, inhalation, eye lotion, ointment or drops, suppository, ointment. cream, lotion, etc.
  • effective amount includes an amount effective, at dosages and for periods of time necessary, to achieve the desired result, e.g., sufficient to treat a hypoactive sexual desire disorder in a subject, and/or the ability of the compound to elicit a desired response in a subject.
  • the term "effective amount,” means an amount sufficient to remedy or improve a disease state, disorder, dysfunction, condition or a symptom, particularly a condition or symptoms associated with obesity, overweightness, undesirable or unwanted weight, weight maintenance, low or poor or a lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence, sexual desire, sexual dysfunction and the like, or otherwise prevent, hinder, retard or reverse the progression of a disease state, disorder, dysfunction, condition, or symptom or any other undesirable symptom associated with the disease, disorder or dysfunction in any way whatsoever.
  • An effective amount of a compound of the present invention may therefore vary according to factors such as the disease state, disorder or dysfunction, age, and weight of the subject, and the ability of the compound of the invention to elicit a desired response in the subject. Dosage regimens may be adjusted to provide the optimum therapeutic response. An effective amount is also one in which any toxic or Attorney Docket No.49848-4030PCT detrimental effects, e.g., side effects, of the compounds of the present invention are outweighed by therapeutically beneficial effects.
  • a “therapeutically effective amount” of compound of the invention may range from about 0.001 to about 30 mg/kg body weight, preferably about 0.01 to about 25 mg/kg body weight, more preferably about 0.1 to about 20 mg/kg body weight, and even more preferably about 1 to about 10 mg/kg, about 2 to about 9 mg/kg, about 3 to about 8 mg/kg, about 4 to about 7 mg/kg, or about 5 to about 6 mg/kg body weight.
  • an effective dosage may range from about 0.001 to about 30 mg/kg body weight, preferably about 0.01 to about 25 mg/kg body weight, more preferably about 0.1 to about 20 mg/kg body weight, and even more preferably about 1 to about 10 mg/kg, about 2 to about 9 mg/kg, about 3 to about 8 mg/kg, about 4 to about 7 mg/kg, or about 5 to about 6 mg/kg body weight.
  • the skilled artisan will appreciate that certain factors may influence the dosage required to effectively treat a subject, including but not limited to the severity of the disease or disorder, previous treatments, the general
  • treatment of a subject with a therapeutically effective amount of a compound of the invention can include a single treatment, acute treatment or chronic treatment, or, preferably, can include a series of treatments.
  • a subject is treated with a compound of the invention in the range of between about 0.1 to about 20 mg/kg body weight, one time per week for between about 1 to about 52 weeks or more, preferably between about 2 to about 8 weeks, more preferably between about 3 to about 7 weeks, and even more preferably for about 4, about 5, or about 6 weeks.
  • treatments can be for as long as necessary to accomplish the treated objective and then for as long as necessary to maintain the achieved objective.
  • a prophylactically effective amount of a compound refers to an amount of a compound of the invention any formula herein or otherwise described herein which is effective, upon single or multiple dose administration to the patient, in preventing or treating a sexual disorder or dysfunction.
  • reduced toxicity is intended to include a reduction in any undesired side effect elicited by a compound of the invention when administered in vivo.
  • treatment limiting toxicity or “treatment limiting side effect(s),” as used herein refers to side effects of a drug or other treatment that are serious enough or severe to the treatment needs to be discontinued.
  • dose limiting refers to side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment.
  • treatment refers to any indicia of success in the treatment or amelioration of an injury, pathology, disease, disorder, condition or symptom, including any objective or subjective parameter such as abatement, remission, diminishing of symptoms or making the injury, pathology, disease, disorder, symptom or condition more tolerable to the patient, slowing in the rate of degeneration or decline, making the final point of degeneration less debilitating; improving a patient's physical or mental well-being.
  • Still other methods presented herein successfully treat body weight and successfully effectuate body weight maintenance of a patient by inducing weight loss in the patient thereby ameliorating symptoms associated with the patient being overweight, and/or maintaining patient weight loss or maintaining a certain weight at which the patient wants maintained or has been prescribed to be maintained, and/or to continue to ameliorate symptoms or conditions associated with a patient being overweight.
  • preventing is art- recognized, and when used in relation to diseases, disorders, symptoms or conditions relating to obesity, overweightness, undesirable or unwanted weight, weight issues, weight maintenance, weight management, SD and/or low or poor or a lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence in a subject are well understood in the art, and includes administration or co-administration of a drug, compound, product, composition, pharmaceutical composition, or agent which reduces the frequency of, or delays the onset of, the disease, disorder, symptom or condition in a subject relative to a subject which does not receive the drug, compound, product, composition, pharmaceutical composition, or agent.
  • the term "susceptible to SD,” such as FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, is meant to include subjects at risk of developing a SD, such as FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, e.g., subjects previously diagnosed as having or having a family or medical history of a SD, such as FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like.
  • systemic administration means the administration of a compound of the invention(s), drug or other material, such that it enters the patient's system and, thus, is subject to metabolism and other like processes, for example, subcutaneous administration.
  • ''compound(s)'' is used herein to refer to a molecular entity, and ''compounds'' may thus have different structural elements besides the minimum element defined for each compound or group of compounds.
  • ''compound(s)'' is also meant to cover pharmaceutically relevant forms hereof, i.e., a compound as defined herein or a pharmaceutically acceptable salt, amide, ester, solvate and the like thereof.
  • Compounds may display extended half-lives gained by substituent addition.
  • a compound may be a drug and/or an API.
  • the term “drug” can also mean (1) a substance recognized by an official pharmacopoeia or formulary, (2) a substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease, (3) a substance (other than food) intended to affect the structure or any function of the body, (4) a substance intended for use as a component of a medicine but not a device or a component, part or accessory of a device.
  • drug product refers to the finished dosage form that contains a drug, generally, but not necessarily in association with other active or inactive ingredients.
  • a “pharmaceutical composition,” as used herein, means a mixture of substances suitable for administering to an individual that includes a pharmaceutical drug, an active pharmaceutical ingredient, or a compound. Generally, they are made of a combination of active pharmaceutical and inactive ingredients to control dosage delivery, enhance performance and appearance, help with absorption, facilitate manufacture and more. Active pharmaceutical ingredient(s), (“API(s),” provide the therapeutic effects of pharmaceutical compositions. Inactive ingredients are also called excipients.
  • a Attorney Docket No.49848-4030PCT pharmaceutical composition may comprise a combination of the present invention and a sterile aqueous solution.
  • an “API” can be a “drug” or a “compound,” a “drug” can be an “API” or a “compound,” and a “compound” can be an “API” or a “drug.”
  • the terms as used herein can mean individually, collectively or interchangeably.
  • a “dosage form” can be a “drug product” or a “pharmaceutical composition”
  • a “drug product” can be a “dosage form” or a “pharmaceutical composition”
  • a pharmaceutical composition can be a “dosage form” or a “drug product,”
  • such terms as used herein can be mean individually, collectively or interchangeably herein.
  • drug release includes various forms of drug release products as defined by the FDA which includes “immediate release” drug products, “modified release” drug products, “delayed release” drug products, and “extended release’ drug products.
  • modified release it refers to drug products wherein the drug release is delayed after its initial administration, i.e., a delayed release drug product, which can be for a prolonged period of time, e.g., an extended release “ER” drug product, “XR” drug product, or an “XL” drug product, or which can be released to a specific target in the body, e.g., a “targeted-release” drug product.
  • a delayed release drug product which can be for a prolonged period of time
  • ER extended release
  • XR drug product
  • XL extended release drug product
  • modified release drug products refer to drug products wherein drug release only occurs sometime after administration or for a prolonged period of time or to a specific target in the body.
  • Modified release drug products can provide therapeutic, or convenience objectives not offered by conventional dosage forms such as drug product solutions or immediate-release dosage drug products.
  • Modified release solid oral dosage forms or drug products include both “delayed release” drug products and “extended release” drug products. See Controlling Drug Delivery, supra. [00250] By “delayed release,” it refers to drug products that release drugs only at some point following initial oral administration of the drug product. See Controlling Drug Delivery, supra. [00251] By “extended release,” it refers to drug products that release drugs over extended periods of time after initial oral administration. Because “extended release” drug products prolong drug release, they allow for a reduction in dosing frequency that may offer dosing and/or therapeutic conveniences over conventional drug products, such as solution drug products or immediate-release drug products. Extended release drug products include sustained release (“SR”) drug products or controlled release (“CR”) drug products. See Controlling Drug Delivery, supra.
  • SR sustained release
  • CR controlled release
  • sustained release it refers to drug products that maintain the rate of drug release over a sustained period of time but not necessarily at a constant rate.
  • sustained release drug products release drugs at a designed rate to maintain constant drug concentration for a selected period of time to maintain efficacy and reduced side effects. See Controlling Drug Delivery, supra.
  • controlled release it refers to drug products that maintain drug release over a sustained period but at a somewhat constant rate. Thus, “extended release” can be achieved using “release” or “controlled release” drug products. See Controlling Drug Delivery, supra.
  • pharmaceutically acceptable refers to those compounds, materials, ingredients, elements, compositions, compositions containing such compounds and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in patients, including in contact with the tissues, organs, and/or bodily fluids of human beings and animals without excessive toxicity, irritation, allergic response, or other problems or complications commensurate with a reasonable benefit/risk ratio.
  • pharmaceutically acceptable includes pharmaceutically acceptable salts, amides, esters and the like.
  • pharmaceutically acceptable carrier includes pharmaceutically acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material, involved in carrying or transporting the subject chemical from one organ, or portion of the body, to another organ, or portion of the body.
  • pharmaceutically acceptable material such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material, involved in carrying or transporting the subject chemical from one organ, or portion of the body, to another organ, or portion of the body.
  • Each carrier is “acceptable” in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient.
  • materials which can serve as pharmaceutically-acceptable carriers include: (1) sugars, such as lactose, glucose and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) Attorney Docket No.49848-4030PCT excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffer
  • “Pharmaceutical excipient(s),” as used herein, are ingredients other than the active pharmaceutical ingredient (API) present in a finished pharmaceutical composition. These are frequently used as lubricants, diluents, carriers, binders, solubilizers, emulsifiers, stabilizers, preservatives, flavorings, coating agents, and coloring agents for the formulation.
  • ''Pharmaceutically acceptable salt(s)'' are non-toxic salts at the concentration at which they are administered.
  • pharmaceutically acceptable salt(s) refers to a formulation of a compound complexed with a salt that does not cause significant irritation to a subject to which it is administered and does not negate the biological activity and properties of the compound.
  • Pharmaceutically acceptable salts include acid addition salts such as those containing sulfate, hydrochloride, phosphate, sulfamate, acetate, citrate, lactate, tartrate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, cyclohexylsulfamate and quinate.
  • Pharmaceutically acceptable salts can be obtained from acids such as hydrochloric acid, sulfuric acid, phosphoric acid, sulfamic acid, acetic acid, citric acid, lactic acid, tartaric acid, malonic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p- toluenesulfonic acid, cyclohexylsulfamic acid, and quinic acid.
  • acids such as hydrochloric acid, sulfuric acid, phosphoric acid, sulfamic acid, acetic acid, citric acid, lactic acid, tartaric acid, malonic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p- toluenesulfonic acid, cyclohexylsulfamic acid, and quinic acid.
  • Such salts may be prepared by, for example, reacting the free acid or base forms of the product with one or more equivalents of the appropriate base or acid in a solvent or medium in which the salt is insoluble, or in a solvent such as water which is then removed in vacuo or by freeze- Attorney Docket No.49848-4030PCT drying or by exchanging the ions of an existing salt for another ion on a suitable ion exchange resin.
  • IR immediate release
  • IR refers to a pharmaceutical composition which may release their contents within minutes of ingestion.
  • controlled release of “CR,” is used herein in its ordinary sense and thus includes pharmaceutical compositions combined or coated with ingredients, such as, rate controlling agents, to alter their dissolution profiles.
  • sustained release or “SR,” or “extended release” or “ER,” or modified release,” of “MR,” as used herein refers to a pharmaceutical composition which is a type of a controlled release formulation wherein the dissolution profile is extended over a longer period of time than that of an immediate release formulation comprising a similar pharmaceutical composition. In other words, these medications prolong the medication’s release from a tablet, caplet or capsule so that the benefits of these medication are received over a longer period of time, which means the medications can be taken less frequently or in fewer doses throughout the day.
  • alkyl refers to the radical of saturated aliphatic groups, including straight-chain alkyl groups, branched-chain alkyl groups, cycloalkyl (alicyclic) groups, alkyl substituted cycloalkyl groups, and cycloalkyl substituted alkyl groups.
  • alkyl further includes alkyl groups, which can further include oxygen, nitrogen, sulfur or phosphorous atoms replacing one or more carbons of the hydrocarbon backbone, e.g., oxygen, nitrogen, sulfur or phosphorous atoms.
  • a straight chain or branched chain alkyl has 30 or fewer carbon atoms in its backbone (e.g., C1- C30 for straight chain, C.sub.3-C.sub.30 for branched chain), preferably 26 or fewer, and more preferably 20 or fewer, and still more preferably 4 or fewer.
  • preferred cycloalkyls have from 3-10 carbon atoms in their ring structure, and more preferably have 3, 4, 5, 6 or 7 carbons in the ring structure.
  • alkyl as used throughout the specification and sentences is intended to include both "unsubstituted alkyls" and “substituted alkyls,” the latter of which refers to alkyl moieties having substituents replacing a hydrogen on one or more carbons of the hydrocarbon backbone.
  • substituents can include, for example, halogen, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate, phosphonato, phosphinato, cyano, amino (including alkyl amino, dialkylamino, acylamino, diarylamino, and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, sulfonato, sulfamoyl, sulfonamido, nitro, trifluoro
  • alkylaryl is an alkyl substituted with an aryl (e.g., phenylmethyl (benzyl)).
  • alkyl also includes unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but that contain at least one double or triple bond respectively.
  • alkenyl and alkynyl refer to unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but that contain at least one double or triple bond, respectively.
  • the invention contemplates cyano and propargyl groups.
  • aryl refers to the radical of aryl groups, including 5- and 6-membered single-ring aromatic groups that may include from zero to four heteroatoms, for example, benzene, pyrrole, furan, thiophene, imidazole, benzoxazole, benzothiazole, triazole, tetrazole, pyrazole, pyridine, pyrazine, pyridazine and pyrimidine, and the like.
  • Aryl groups also include polycyclic fused aromatic groups such as naphthyl, quinolyl, indolyl, and the like.
  • aryl groups having heteroatoms in the ring structure may also be referred to as "aryl heterocycles," “heteroaryls” or “heteroaromatics.”
  • the aromatic ring can be substituted at one or more ring positions with such substituents as described above, as for example, halogen, hydroxyl, alkoxy, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylthiocarbonyl, phosphate, phosphonato, phosphinato, cyano, amino (including alkyl amino, dialkylamino, arylamino, diarylamino, and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino, imino, s
  • Aryl groups can also be fused or bridged with alicyclic or heterocyclic rings which are not aromatic so as to form a polycycle (e.g., tetralin).
  • the term "associating with” refers to a condition of proximity between a chemical entity or compound, or portions thereof, and a binding pocket or binding site on a protein. The association may be non-covalent (wherein the juxtaposition is energetically favored by hydrogen bonding or van der Waals or electrostatic interactions) or it may be covalent.
  • Attorney Docket No.49848-4030PCT [00269]
  • biological activities" of a compound of the present invention includes all activities elicited by compound of the inventions in a responsive cell.
  • Bio composition refers to a composition containing or derived from cells or biopolymers.
  • Cell-containing compositions include, for example, mammalian blood, red cell concentrates, platelet concentrates, leukocyte concentrates, blood cell proteins, blood plasma, platelet-rich plasma, a plasma concentrate, a precipitate from any fractionation of the plasma, a supernatant from any fractionation of the plasma, blood plasma protein fractions, purified or partially purified blood proteins or other components, serum, semen, mammalian colostrum, milk, saliva, placental extracts, a cryoprecipitate, a cryosupernatant, a cell lysate, mammalian cell culture or culture medium, products of fermentation, ascites fluid, proteins induced in blood cells, and products produced in cell culture by normal or transformed cells (e.g., via recombinant DNA or monoclonal antibody technology).
  • Biological compositions can be cell-free.
  • a suitable biological composition or biological sample is a red blood cell suspension.
  • the blood cell suspension includes mammalian blood cells.
  • the blood cells are obtained from a human, a non-human primate, a dog, a cat, a horse, a cow, a goat, a sheep or a pig.
  • the blood cell suspension includes red blood cells and/or platelets and/or leukocytes and/or bone marrow cells.
  • the term "chiral" refers to molecules which have the property of non- superimposability of the mirror image partner, while the term “achiral” refers to molecules which are superimposable on their mirror image partner.
  • diastereomers refers to stereoisomers with two or more centers of dissymmetry and whose molecules are not mirror images of one another.
  • enantiomers refers to two stereoisomers of a compound which are non-superimposable mirror images of one another.
  • An equimolar mixture of two Attorney Docket No.49848-4030PCT enantiomers is called a "racemic mixture” or a “racemate.”
  • the compounds of this invention may contain one or more asymmetric centers and thus occur as racemates and racemic mixtures, single enantiomers, individual diastereomers and diastereomeric mixtures. All such isomeric forms of these compounds are expressly included in the present invention.
  • haloalkyl is intended to include alkyl groups as defined above that are mono-, di- or polysubstituted by halogen, e.g., fluoromethyl and trifluoromethyl.
  • halogen designates --F, --Cl, --Br or --I.
  • hydroxyl means --OH.
  • heteroatom as used herein means an atom of any element other than carbon or hydrogen. Preferred heteroatoms are nitrogen, oxygen, sulfur and phosphorus.
  • homeostasis is art-recognized to mean maintenance of static, or constant, conditions in an internal environment.
  • improved biological properties refers to any activity inherent in a compound of the invention that enhances its effectiveness in vivo. In a preferred embodiment, this term refers to any qualitative or quantitative improved therapeutic property of a compound of the invention, such as effectiveness and/or reduced toxicity.
  • Such optional substituents include, for example, hydroxy, halogen, cyano, nitro, C1-C8alkyl, C2-C8alkenyl, C2-C8alkynyl, C1-C8alkoxy, C2-C8alkyl ether, C3- C8alkanone, C1-C8alkylthio, amino, mono- or di-(C1-C8alkyl)amino, haloC1-C8alkyl, haloC1-C8alkoxy, C1- C8alkanoyl, C2-C8alkanoyloxy, C1-Calkoxycarbonyl, --COOH, --CONH2, mono- or di-(C1- C8alkyl)aminocarbonyl, --SO2NH2, and/or mono or di(C1-C8alkyl)sulfonamido, as well as carbocyclic and heterocyclic groups.
  • substitution is also indicated by the phrase "substituted with from 0 to X substituents," where X is the maximum number of possible substituents.
  • Certain optionally substituted groups are substituted with from 0 to 2, 3 or 4 independently selected substituents, i.e., are unsubstituted or substituted with up to the recited maximum number of substituents.
  • the term “isomers” or “stereoisomers” refers to compounds which have identical chemical constitution but differ with regard to the arrangement of the atoms or groups in space.
  • the term “modulate” refers to an increase or decrease, e.g., the alteration in a SD, such as FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, and/or symptoms thereof in a subject such that a desired end result is achieved, e.g., a therapeutic result.
  • the term “obtaining” as in "obtaining a compound useful in treating hypoactive sexual desire disorder” is intended to include purchasing, synthesizing or otherwise acquiring the compound.
  • parenteral administration and “administered parenterally” as used herein means modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, Attorney Docket No.49848-4030PCT intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticulare, subcapsular, subarachnoid, intraspinal and intrasternal injection and infusion.
  • polycyclyl or “polycyclic radical” refer to the radical of two or more cyclic rings (e.g., cycloalkyls, cycloalkenyls, cycloalkynyls, aryls and/or heterocyclyls) in which two or more carbons are common to two adjoining rings, e.g., the rings are "fused rings". Rings that are joined through non-adjacent atoms are termed "bridged" rings.
  • Each of the rings of the polycycle can be substituted with such substituents as described above, as for example, halogen, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate, phosphonato, phosphinato, cyano, amino (including alkylamino, dialkylamino, arylamino, diarylamino, and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, sulfonato, sulfamoyl
  • prodrug or "pro-drug” includes compounds with moieties that can be metabolized in vivo.
  • the prodrugs are metabolized in vivo by esterases or by other mechanisms to active drugs.
  • Examples of prodrugs and their uses are well known in the art. See, e.g., Berge et al.; "Pharmaceutical Salts", J. Pharm. Sci.1977;66:1- 19.
  • the prodrugs can be prepared in situ during the final isolation and purification of the compounds, or by separately reacting the purified compound in its free acid form or hydroxyl with a suitable esterifying agent. Hydroxyl groups can be converted into esters via treatment with a carboxylic acid.
  • prodrug moieties include substituted and unsubstituted, branch or unbranched lower alkyl ester moieties, e.g., propionoic acid esters, lower alkenyl esters, di-lower alkyl-amino lower-alkyl esters, e.g., dimethylaminoethyl ester, acylamino lower alkyl esters, e.g., acetyloxymethyl ester, acyloxy lower alkyl esters, e.g., pivaloyloxymethyl ester), aryl esters (phenyl ester), aryl- lower alkyl esters, e.g., benzyl ester, substituted, e.g., with methyl, halo, or methoxy substituents aryl and aryl-lower alkyl esters, amides, lower-alkyl amides, di-lower alkyl Attorney Docket No.49848-4030
  • prodrug moieties are propionoic acid esters and acyl esters.
  • Prodrugs which are converted to active forms through other mechanisms in vivo are also included.
  • d and l configuration are as defined by the IUPAC Recommendations.
  • diastereomer, racemate, epimer and enantiomer will be used in their normal context to describe the stereochemistry of preparations.
  • compositions of the present invention may be formulated, so as to release their contents after a time lag, or a little at a time, or in some other predetermined way and are referred to as “time-release” formulations, that include controlled release, sustained release, extended release and modified release pharmaceutical compositions.
  • time-release formulations that include controlled release, sustained release, extended release and modified release pharmaceutical compositions.
  • Many pharmaceutical compositions are time-release formulated to reduce their drugs local adverse effects in the gastrointestinal tract, to reduce adverse effects associated with the drugs peak blood levels, or to artificially extend the half-life of the drugs. Time-release formulations are associated with the added advantages of convenience of dosing, improved compliance, and less fluctuation in blood levels across the course of the day.
  • trazodone preferably refers to the active pharmaceutical ingredient “trazodone hydrochloride”.
  • bupropion and trazodone or their pharmaceutical salts are sometimes commonly referred to as “drugs”.
  • a preferable effective amount of bupropion for treating subjects who are not obese ranges from about 326 mg to about 334 mg, and more preferably about 329.5 mg.
  • a preferable effective amount of trazodone for treating subjects who are not obese ranges from about 124 mg to about 132 mg, and more preferably about 128.5 mg.
  • compositions of the present invention comprise bupropion or pharmaceutically acceptable salt thereof in a dose range of about 326 mg to about 334 mg, and trazodone or pharmaceutically acceptable salt thereof in a dose range of about 124 mg to about 132 mg.
  • the present invention also contemplates a pharmaceutical composition comprising bupropion or a pharmaceutically acceptable salt thereof in a dose amount of about 329.5 mg and trazodone or pharmaceutically acceptable salt thereof in a dose range amount of about 128.5 mg.
  • a preferable effective amount of bupropion for treating subjects who are obese, a body mass of 30 kg/m 2 or greater ranges from about 366 to about 374 mg, and more preferably about 369.5 mg.
  • a preferable effective amount of trazodone for treating subjects who are not obese, including those with a body mass under 30 kg/m 2 , including overweight subjects with a body mass of 27 kg/m 2 or greater ranges from about 139 to about 147 mg, and more preferably about 143.5 mg.
  • pharmaceutical compositions of the present invention comprise bupropion or pharmaceutically acceptable salt thereof in a dose range of about 366 mg to about 374 mg, and trazodone or pharmaceutically acceptable salt thereof in a dose range of about 139 mg to about 143.5 mg.
  • the present invention also contemplates a pharmaceutical composition comprised of bupropion or a pharmaceutically acceptable salt thereof in a dose amount of about 369.5 mg and trazodone or pharmaceutically acceptable salt thereof in a dose range amount of about 143.5 mg.
  • an effective amount of bupropion or a pharmaceutically acceptable salt thereof and an effective amount of trazodone or a pharmaceutically acceptable salt thereof, as contemplated by the present invention are any amount that accomplishes the objectives of the present invention, including those amounts and ranges provided herein.
  • bupropion or a pharmaceutically acceptable salt thereof and/or trazodone or a pharmaceutically acceptable salt thereof in a pharmaceutical composition of the present invention exhibit sustained release drug delivery upon oral consumption by a subject.
  • each of bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt in a pharmaceutical composition of the present invention exhibit sustained release drug delivery upon oral consumption by a subject.
  • the bupropion or a pharmaceutically acceptable salt thereof and trazodone or a pharmaceutically acceptable salt thereof are each administered as time-release, once-a-day or twice-a-day medications for delivering the effective amounts of bupropion and trazodone to the treated subjects.
  • the mechanism by which the combination of trazodone SR and bupropion SR induces weight loss is not entirely understood and remains unclear.
  • SR bupropion is thought to have effects on areas of the brain involved in the regulation of food intake, sexual desire, sexual fantasies, sexual function and/or low or poor or a lack of a subjective state or sense of well-being, self-esteem, and/or self-confidence.
  • SR Trazodone and/or its metabolite mCPP is thought to reduce or modulate serotonin and possibly activate the 5-HT2C receptors possibly contributing to a decrease in appetite and satiety and affect mood.
  • Trazodone through improved sleep may also play a role in added weight benefits - better sleep generally with better BMI/non-weight gain; or rather that poor sleep correlates with unhealthy weight gain.
  • the combination achieves the objectives of the present invention: ⁇ By decreasing or modulating serotonin levels and increasing dopamine and norepinephrine levels, the combination induces weight loss or affects weight.
  • the combinations of the present invention work by directly and uniquely targeting the CNS by, for example, (a) inducing physiological effects from dopaminergic and noradrenergic modulation of energy, (b) increasing glucagon release and lipolysis, (c) stimulating the reward circuity, (d) stimulating prosexual benefit mechanisms, (d) counteracting certain sexual inhibitory mechanisms, (e) improving sleep, etc., and thus are able to uniquely and remarkably accomplish the objectives of the present invention that include, amongst other things, inducing and/or maintaining weight loss, improving sexual desire and function, and/or improving the subjective state or sense of well-being, self-esteem, and/or self-confidence.
  • the bupropion and trazodone combinations of the present invention when administered in the novel ratios and dosage strengths disclosed herein, uniquely and unexpectedly coordinate their mechanisms and their targets to amplify desired Attorney Docket No.49848-4030PCT effects, simultaneously placing unwanted effects in opposition for a perceived cancellation of side effects, i.e., they uniquely exploit their different mechanisms and targets to stimulate the prosexual benefit and weight loss pathways while inhibiting the inhibitory sexual desire pathways to improve sexual desire and function, to induce and/or maintain weight loss and/or improve the subjective state or sense of well-being, self- esteem, and/or self-confidence.
  • the compounds delineated herein include a 5-HT2A antagonist, that is a compound that demonstrates antagonistic activity against the 5-HT2A receptor; a norepinephrine-dopamine reuptake inhibitor; that is a compound that exhibits inhibition activity in norepinephrine-dopamine reuptake; a 5-HT1A receptor agonist, that is a compound that demonstrates agonist activity against the 5-HT1A receptor; and an endocrine active agent, that is an agent that is active in modulating the endocrine system.
  • the invention provides a compound (e.g., a compound herein) capable of modulating hypoactive sexual desire disorder; and pharmaceutically acceptable esters, salts, isomers and prodrugs thereof.
  • a compound e.g., a compound herein
  • Naturally occurring or synthetic isomers can be separated in several ways known in the art. Methods for separating a racemic mixture of two enantiomers include chromatography using a chiral stationary phase (see, e.g., "Chiral Liquid Chromatography," W. J. Lough, Ed. Chapman and Hall, New York (1989)). Enantiomers can also be separated by classical resolution techniques.
  • diastereomeric salts and fractional crystallization can be used to separate enantiomers.
  • the diastereomeric salts can be formed by addition of enantiomerically pure chiral bases such as brucine, quinine, ephedrine, strychnine, and the like.
  • diastereomeric esters can be formed with enantiomerically pure chiral alcohols such as menthol, followed by separation of the diastereomeric esters and hydrolysis to yield the free, enantiomerically enriched carboxylic acid.
  • the invention provides methods of treating hypoactive sexual desire disorder (HSDD) in a subject comprising administering to the subject a composition delineated herein.
  • the subject is a mammal, e.g., a primate, e.g., a human.
  • the disease, disorder or symptom thereof in which the compounds, compositions, and methods of treatment relate to is one described in the Diagnostic and Statistical Manual of Mental Disorders 4.sup.th edition--Text Revision, (DSM-I-TRV), American Psychiatric Association.
  • the methods of the invention include administering to a subject a therapeutically effective amount of a compound of the invention in combination with another pharmaceutically active compound.
  • pharmaceutically active compounds include compounds known to treat hypoactive sexual desire disorder (HSDD) in a subject.
  • HSDD hypoactive sexual desire disorder
  • Other pharmaceutically active compounds that may be used can be found in Harrison's Principles of Internal Medicine, Thirteenth Edition, Eds. T. R. Harrison et al.
  • HSDD therapeutically effective hypoactive sexual desire disorder
  • prophylactically effective hypoactive sexual desire disorder amount of the compound of the invention can be readily made by the physician or veterinarian (the "attending clinician"), as one skilled in the art, by the use of known techniques and by observing results obtained under analogous circumstances.
  • the dosages may be varied depending upon the requirements of the patient in the judgment of the attending clinician; the severity of the condition being treated and the particular compound being employed.
  • a number of factors are considered by the attending clinician, including, but not limited to: the specific hypoactive sexual desire disorder involved; pharmacodynamic characteristics of the particular agent and its mode and route of administration; the desired time course of treatment; the species of mammal; its size, age, and general health; the specific disease involved; the degree of or involvement or the severity of the disease; the response of the individual patient; the particular compound administered; the mode of administration; the bioavailability characteristics of the preparation administered; the dose regimen selected; the kind of concurrent treatment (i.e., the interaction of the compound of the invention with other co-administered therapeutics); and other relevant circumstances.
  • the dosage administration can be in a single dosage form or multiple dosage forms.
  • the dosages can be administered concurrently, simultaneously, or sequentially.
  • the dosages can be a single dosage immediately prior to sexual activity or can be one or more doses daily without regard to timing prior to sexual activity.
  • Treatment can be initiated with smaller dosages, which are less than the optimum dose of the compound. Thereafter, the dosage may be increased by small increments until the optimum effect under the circumstances is reached.
  • the total daily dosage may be divided and administered in portions during the day if desired.
  • a Attorney Docket No.49848-4030PCT therapeutically effective amount and a prophylactically effective amount of a compound of the invention of the invention is expected to vary from about 0.1 milligram per kilogram of body weight per day (mg/kg/day) to about 100 mg/kg/day.
  • Certain of the methods for identification of patients which are at risk of developing SD such as FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, and/or low or poor or a lack of a subjective state of well-being, self-esteem, and/or self-confidence which can be treated by the subject method are appreciated in the medical arts, such as family history, and the presence of risk factors associated with the development of that disease state in the subject patient (e.g., use of antidepressant drugs, hormonal contraceptives, antihormonal and/or cytotoxic chemotherapies, sedatives, antipsychotic drugs, antiepileptic drugs, antidepressive drugs, opioid drugs, alcohol, or narcotic drugs).
  • the subject may be at risk of a SD, such as FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, may be exhibiting symptoms of a SD, such as FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, may be susceptible to a SD, such as FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, and/or may have been diagnosed with a SD, such as SD, e.g., FSD, HSDD, FSAD, FOD, and/or
  • Kits of the invention include kits for treating a hypoactive sexual desire disorder in a subject.
  • the kit may include a compound of the invention, for example, a compound described herein, pharmaceutically acceptable esters, salts, and prodrugs thereof, and instructions for use.
  • the instructions for use may include information on dosage, method of delivery, storage of the kit, etc.
  • the present invention also provides a pharmaceutical composition, comprising an effective amount of a compound described herein and a pharmaceutically acceptable carrier.
  • the effective amount is effective to treat obesity, weight loss and/or maintain weight loss, as described previously.
  • the effective amount is effective to treat obesity, weight loss, undesirable or unwanted weight, and/or maintain weight loss and the effective amount is effective to treat SD, such as FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD, including ED, PD, PE, MHSDD, delayed ejaculation, decreased libido, dry orgasm, and the like, low or poor or a lack of a subjective state of well-being, self-esteem, and/or self-confidence, as described previously.
  • SD such as FSD, HSDD, FSAD, FOD, FSIAD, and/or MSD
  • ED ED
  • PD PE
  • MHSDD delayed ejaculation
  • decreased libido dry orgasm
  • the compound of the invention is administered to the subject using a pharmaceutically acceptable formulation, e.g., a pharmaceutically acceptable formulation that provides sustained delivery of the compound of the invention to a subject for at least 12 hours, 24 hours, 36 hours, 48 hours, one week, two weeks, three weeks, or four weeks or more after the pharmaceutically acceptable formulation is administered to the subject.
  • a pharmaceutically acceptable formulation e.g., a pharmaceutically acceptable formulation that provides sustained delivery of the compound of the invention to a subject for at least 12 hours, 24 hours, 36 hours, 48 hours, one week, two weeks, three weeks, or four weeks or more after the pharmaceutically acceptable formulation is administered to the subject.
  • the pharmaceutical compositions as contemplated by the present invention are suitable for topical or oral, buccal or sublingual administration to a subject.
  • wetting agents such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, release agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the compositions.
  • antioxidants examples include: (1) water soluble antioxidants, such as ascorbic acid, cysteine hydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfite and the like; (2) oil-soluble antioxidants, such as ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), lecithin, propyl gallate, alpha-tocopherol, and the like; and (3) metal chelating agents, such as citric acid, ethylenediamine tetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid, and the like.
  • water soluble antioxidants such as ascorbic acid, cysteine hydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfite and the like
  • oil-soluble antioxidants such as ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), le
  • compositions containing a compound of the present invention(s) include those suitable for oral, nasal, topical (including buccal and sublingual), rectal, vaginal, aerosol and/or parenteral administration.
  • the compositions may conveniently be presented in unit dosage form and may be prepared by any methods well known in the art of pharmacy.
  • the amount of active ingredient which can be combined with a carrier material to produce a single dosage form will vary depending upon the host being treated, the particular mode of administration.
  • the amount of active ingredient which can be combined with a carrier material to produce a single dosage form will generally be that amount of the compound which produces a therapeutic effect.
  • compositions include the step of bringing into association a compound of the invention(s) with the carrier and, optionally, one or more accessory ingredients.
  • the formulations are prepared by uniformly and intimately bringing into association a compound of the invention with liquid carriers, or finely divided solid carriers, or both, and then, if necessary, shaping the product.
  • compositions of the invention suitable for oral administration may be in the form of capsules, cachets, caplets, capsules, dragees, granules, films, lozenges (using a flavored basis, usually sucrose and acacia or tragacanth), pills, tablets, troches, or as a solution or a suspension in an aqueous or non- aqueous liquid, or as an oil-in-water or water-in-oil liquid emulsion, or as an elixir or syrup, or as pastilles (using an inert base, such as gelatin and glycerin, or sucrose and acacia) and/or as mouth washes and the like, each containing a predetermined amount of a compound of the invention(s) as an active ingredient.
  • lozenges using a flavored basis, usually sucrose and acacia or tragacanth
  • pills pills, tablets, troches, or as a solution or a suspension in an aqueous or non- aque
  • the tablets, and other solid dosage forms of the pharmaceutical compositions of the present invention may optionally be scored or prepared with coatings and shells, such as enteric coatings and other coatings well known in the pharmaceutical-formulating art. They may also be formulated so as to provide slow or controlled release of the active ingredient therein using, for example, hydroxypropyl methyl cellulose in varying proportions to provide the desired release profile, other polymer matrices, liposomes and/or microspheres.
  • compositions may be sterilized by, for example, filtration through a bacteria- retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved in sterile water, or some other sterile injectable medium immediately before use.
  • These compositions may also optionally contain opacifying agents and may be of a composition that they release the active ingredient(s) only, or preferentially, in a certain portion of the gastrointestinal tract, optionally, in a delayed manner.
  • embedding compositions which can be used include polymeric substances and waxes.
  • the active ingredient can also be in micro- encapsulated form, if appropriate, with one or more of the above-described excipients.
  • the liquid dosage forms may contain inert diluents commonly used in the art, such as, for example, water or other solvents, solubilizing agents and emulsifiers, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor and sesame oils), glycerol, tetrahydrofuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof.
  • inert diluents commonly used in the art, such as, for example, water or other solvents, solubilizing agents and emulsifiers, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol,
  • the oral compositions can include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, coloring, perfuming and preservative agents.
  • adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, coloring, perfuming and preservative agents.
  • Suspensions in addition to the active compound of the invention(s) may contain suspending agents as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, and mixtures thereof.
  • compositions of the invention for rectal or vaginal administration may be presented as a suppository, which may be prepared by mixing one or more compound of the invention(s) with one or more suitable nonirritating excipients or carriers comprising, for example, cocoa butter, polyethylene glycol, a suppository wax or a salicylate, and which is solid at room temperature, but liquid at body temperature and, therefore, will melt in the rectum or vaginal cavity and release the active agent.
  • suitable nonirritating excipients or carriers comprising, for example, cocoa butter, polyethylene glycol, a suppository wax or a salicylate, and which is solid at room temperature, but liquid at body temperature and, therefore, will melt in the rectum or vaginal cavity and release the active agent.
  • Pharmaceutical compositions of the present invention which are suitable for vaginal administration also include pessaries, tampons, creams, gels, pastes, foams or spray formulations containing such carriers as are known in the art to be appropriate
  • the ointments, pastes, creams and gels may contain, in addition to compound of the invention(s) of the present invention, excipients, such as animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide, or mixtures thereof.
  • excipients such as animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide, or mixtures thereof.
  • Powders and sprays can contain, in addition to a compound of the invention(s), excipients such as lactose, talc, silicic acid, aluminum hydroxide, cyclodextrins, HPMCs, calcium silicates and polyamide powder, or mixtures of these substances.
  • Sprays can additionally contain customary propellants, such as chlorofluorohydrocarbons and volatile unsubstituted hydrocarbons, such as butane and propane.
  • customary propellants such as chlorofluorohydrocarbons and volatile unsubstituted hydrocarbons, such as butane and propane.
  • the compound of the present invention(s) can be alternatively administered by aerosol. This is accomplished by preparing an aqueous aerosol, liposomal preparation or solid particles containing the compound. A nonaqueous (e.g., fluorocarbon propellant) suspension could be used. Sonic nebulizers are preferred because they minimize exposing the agent to shear, which can result in degradation of the compound.
  • an aqueous aerosol is made by formulating an aqueous solution or suspension of the agent together with conventional pharmaceutically-acceptable carriers and stabilizers,
  • the carriers and stabilizers vary with the requirements of the particular compound, but typically include nonionic surfactants (Tweens, Pluronics, or polyethylene glycol), innocuous proteins like serum albumin, sorbitan esters, oleic acid, lecithin, amino acids such as glycine, buffers, salts, sugars or sugar alcohols.
  • Aerosols generally are prepared from isotonic solutions.
  • Transdermal patches have the added advantage of providing controlled delivery of a compound of the invention(s) to the body.
  • dosage forms can be made by dissolving or dispersing the agent in the proper medium.
  • Absorption enhancers can also be used to increase the flux of the active ingredient across the skin. The rate of such flux can be controlled by either providing a rate controlling membrane or dispersing the active ingredient in a polymer matrix or gel.
  • Ophthalmic formulations, eye ointments, powders, solutions and the like, are also contemplated as being within the scope of the invention.
  • compositions of the invention suitable for parenteral administration comprise one or more compound of the invention(s) in combination with one or more pharmaceutically-acceptable sterile isotonic aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, or sterile powders which may be reconstituted into sterile injectable solutions or dispersions just prior to use, which may contain antioxidants, buffers, bacteriostats, solutes which render the formulation isotonic with the blood of the intended recipient or suspending or thickening agents.
  • aqueous and nonaqueous carriers examples include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, and the like), and suitable mixtures thereof, vegetable oils, such as olive oil, and injectable organic esters, such as ethyl oleate.
  • polyols such as glycerol, propylene glycol, polyethylene glycol, and the like
  • vegetable oils such as olive oil
  • injectable organic esters such as ethyl oleate.
  • Proper fluidity can be maintained, for example, by the use of coating materials, such as lecithin, by the maintenance of the required particle size in the case of dispersions, and by the use of surfactants.
  • the pharmaceutical compositions may also contain adjuvants such as preservatives, wetting agents, emulsifying agents and dispersing agents.
  • Injectable depot forms are made by forming microencapsule matrices of compound of the invention(s) in biodegradable polymers such as polylactide- polyglycolide. Depending on the ratio of drug to polymer, and the nature of the particular polymer employed, the rate of drug release can be controlled.
  • biodegradable polymers examples include poly(orthoesters) and poly(anhydrides). Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemuisions which are compatible with body tissue.
  • a pharmaceutical composition containing, for example, 0.1 to 99.5% (more preferably, 0.5 to 90%) of active ingredient in combination with a pharmaceutically acceptable carrier.
  • the compound of the invention(s), which may be used in a suitable hydrated form, and/or the pharmaceutical compositions of the present invention, are formulated into pharmaceutically acceptable dosage forms by conventional methods known to those of skill in the art.
  • Attorney Docket No.49848-4030PCT [00355]
  • Actual dosage levels and time course of administration of the active ingredients in the pharmaceutical compositions of the present invention may be varied so as to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient.
  • An exemplary dose range is from 0.1 to 10 mg per day.
  • a preferred dose of the compound of the present invention is the maximum that a patient can tolerate and not develop serious side effects.
  • the compound of the invention of the present invention is administered at a concentration of about 0.001 mg to about 100 mg per kilogram of body weight, about 0.001--about 10 mg/kg or about 0.001 mg--about 100 mg/kg of body weight. Ranges intermediate to the above-recited values are also intended to be part of the invention. [00357] It should be understood that the methods of the present invention contemplate the use of any compounds, pharmaceutical compositions formulated compounds, and FDA-approved drug compounds discussed herein in accordance with their respective FDA-approved labels, including their respective FDA-approved dosage strengths and treatment regimens.
  • a particular dosage and treatment regimen for compound drug combinations contemplated by the methods of the present invention will depend upon the combination of the drug compounds prescribed, dosage strengths and treatment regimens, including FDA approved dosage strengths and treatment regimens, the status of the patients and the severity of the nature of the conditions to be treated.
  • the combination drug compositions of the present invention should be prescribed by a physician or health professional, preferably a treating physician, who will consider any relevant factors, such as the patients' diagnosed condition(s) to be treated, the patients’ age and weight, the patients’ symptoms, the severity of the patients’ symptoms, the drugs and/or drug cocktails of choice to treat the patients’ diagnosed condition(s), the treatment regimens, the dosage strengths, and the chosen routes of administration.
  • the present invention also contemplates the safe and effective use of other dosage strengths and treatment regimens, even those that are not necessarily FDA-approved, i.e., off label use, for the drug compound combinations Attorney Docket No.49848-4030PCT disclosed herein in accordance with the methods of the present invention when prescribed by a physician or other health care professional who has taken into careful consideration medical publications and possible advice from experts supporting such use.
  • the present disclosure will further be illustrated in the following non-limiting examples, it being understood that the examples are intended to be illustrative only and that the disclosure is not intended to be limited to the materials, conditions, process parameters and the like recited herein. All proportions are by weight unless otherwise indicated.
  • Bupropion is also known as, i.e., ⁇ -Keto-3-chloro-N-tert-butylamphetamine, i.e., ( ⁇ )-2-(tert-Butylamino)-1-(3- chlorophenyl)propan-1-one;
  • trazodone is also known as, i.e., 2- ⁇ 3-[4-(3- chlorophenyl)piperazin-1-yl]propyl ⁇ [1,2,4]triazolo[4,3-a]pyrid- in-3(2H)-one.
  • Example 1 [00362] Clinical protocol—subjects in a single blind, sequential study are administered bupropion and trazodone in increasing dosages @ 3-4 weeks each, that is, from a 3 (or 4)-week placebo baseline, to an intermediate dose (@ another 3-4 weeks), to a maximum dose (@ a final 3-4 weeks).
  • the subjects' feedback/reports on subjective (e.g., feelings, sensations, general response) and objective (e.g., response time, performance measures, partner response) are collated and analyzed against dosage.
  • Each study also includes one or more patient(s) serving as a control (in demonstrating Attorney Docket No.49848-4030PCT the synergistic effect between the two actives) receives only bupropion, while the second and third will each be given a different fixed dose combination products having a defined ratio of active ingredients (e.g., bupropion and trazodone).
  • a control in demonstrating Attorney Docket No.49848-4030PCT the synergistic effect between the two actives
  • receives only bupropion receives only bupropion, while the second and third will each be given a different fixed dose combination products having a defined ratio of active ingredients (e.g., bupropion and trazodone).
  • active ingredients e.g., bupropion and trazodone
  • the mean score with Llow and Lhigh was about twice that with Treatment B (two-tailed paired t-test, p ⁇ 0.0001), and Treatment B was superior to Treatment T.
  • Llow was associated with somewhat more improvements than with Treatment B in the third and fourth weeks of use.
  • Lhigh was associated with significantly more improvements than with Treatment B in the third and fourth weeks of use and in the total for all four weeks. Fisher's exact test, two-tailed, showed the combination of bupropion plus trazodone superior, p ⁇ 0.05, for the 3-domain sum of sexual event improvement.
  • the independent researcher when told that the results were positive for the subject but before seeing any of the data, decided to apply categorical tests to the most obvious comparisons between treatments: for the first two weeks, the second two weeks, and for all four weeks of treatment, low-dose combination of bupropion plus trazodone vs. corresponding dose of bupropion; and high-dose the combination of bupropion plus trazodone vs. same dose of trazodone.
  • the test used for the desired score was a two-tailed paired t test.
  • the test used for the two-category variables was an online two-tailed Fisher's exact test. Both were from the website graphpad.com.* See Table 1. [00367] *http://graphpad.com/quickcalcs/chisquared1.cfm
  • Week 0 Informed consent, screening evaluations [Medical, psychiatric, social/relationship, and sexual history; diagnostics], measures of sexual dysfunction, and safety evaluations [physical examination, ECG, standard laboratory safety analytes] [00379]
  • Week 1 Treatment #1 [00380] Group 1 [00381] Low Dose combination of bupropion plus trazodone: 250 mg BUP+75 mg TRZ/day, given as 150 mg SR BUP in the morning and 100 mg SR BUP in the evening and 75 mg SR trazodone q.d.; and test battery.
  • the test battery includes single-dose PK, steady-state PK and pharmacodynamics.
  • Pharmacodynamics includes a cognitive test battery and numeric rating scales (NRS) of feeling states, which will be done in the morning of the first and last day of dosing, at pre-dose and at 1-, 2-, 4- and 8-hours post- dose.
  • the cognitive testing battery includes choice reaction time, word recall, picture recognition, numeric and spatial working memory.
  • the self-rated NRS of feeling states for sedation/activation includes drowsy, dizzy, nervous, agitated, and hyper. Cognitive testing will be done within -20 minutes before the hour; blood sampling will be done exactly on the hour; and VAS will be done within +15 minutes after the hour.
  • compositions of the invention can be made by combining the active agents (i.e., bupropion and trazodone) with one or more of the following excipients: [00395] CARNAUBA WAX, CYSTEINE HYDROCHLORIDE, HYPROMELLOSES, MAGNESIUM STEARATE, CELLULOSE, MICROCRYSTALLINE, POLYETHYLENE, GLYCOL, POLYSORBATE 80, TITANIUM DIOXIDE, FD&C BLUE NO.1; [00396] Hydroxypropyl distarch phosphate (Contramid®), Hypromellose, Sodium stearyl fumarate, Colloidal silicon dioxide, Iron Oxide Yellow, Iron Oxide Red, Talc, Polyethylene Glycol 3350, Titanium Dioxide, Polyvinyl Alcohol, Black ink (food grade).
  • active agents i.e., bupropion and trazodone
  • LOR-low low-dose bupropion + trazodone
  • LOR-mod moderate-dose bupropion + trazodone
  • the order of treatments was a daily standard dose of bupropion; a daily subtherapeutic dose of SR bupropion and SR trazodone (LOR-low); and a daily threshold-therapeutic dose of SR bupropion and SR trazodone (LOR-mod).
  • LOR-mod a daily threshold-therapeutic dose of SR bupropion and SR trazodone
  • the study's primary objective was to evaluate bupropion/trazodone combination safety, tolerability and prosexual efficacy of the bupropion/trazodone combination as compared to bupropion, one of its constituent drugs. Other objectives included exploration of the onset and duration of action of the bupropion/trazodone combination. [00405]
  • the study had an adaptive, three-way crossover, open-label design. It enrolled 30 premenopausal women who met the DSM-IV-TR criteria for HSDD, and it also assessed patients for the newly defined DSM-5 Sexual Interest and Arousal Disorder.
  • Bupropion SR 150 mg was administered once daily in the morning and trazadone ER 75 mg was administered once daily at bedtime (“LOR-low”), each for four weeks.
  • Moderate Dose is also combination therapy that consist of two modified release or delayed release drugs: bupropion and trazadone.
  • Bupropion SR 150 mg was administered twice daily, once in the morning and once eight (8) hours later, and trazadone ER 150 mg was administered once daily at bedtime (“LOR-mod”), each for four weeks.
  • Attorney Docket No.49848-4030PCT [00410] Patients self-evaluated weekly with questionnaires and were assessed during eight clinic visits.
  • Outcome measures for efficacy included validated self-rated scales of Sexual Function and Sexual Distress and global change.
  • Bupropion SR at 300 mg/day and a washout was followed by four weeks of Lorexys low- dose (LOR-low), i.e., Bupropion SR plus Trazodone ER at doses lower than the labeled doses, followed by another washout and four weeks of Lorexys moderate-dose (LOR-mod; 2x LOR-low).
  • LOR-low Lorexys low- dose
  • the primary efficacy endpoint was Female Sexual Function Index Desire domain (FSFI-d); the key secondary was Female Sexual Distress Scale-Revised (FSDS-R).
  • Tables 6-10 illustrate tabulated individualized and group weight loss results from the four-week open label study described in this Example 5. Tables 6-8 are a continuation for each of the 24 subject numbers identified vertically at the start of Table 6. [00425] Table 11 is a list of abbreviation definitions used in Tables 5-10. [00426] Table 6 - Tabulated Individualized and Group Weight Loss Results Attorney Docket No.49848-4030PCT [00427] Table 7 - Tabulated Individualized and Group Weight Loss Results (Table 6 continued)
  • Table 8 Tabulated Individualized and Group Weight Loss Results (Table 6 continued)
  • Table 9 is a composite of Tables 6-8 and 11 and illustrates tabulated individualized and group weight loss or gain results from the four-week open label study described in this Example 5.
  • Table 9 A Composite of Tables 6-8 and 11
  • Table 10 is a listing of the individual weight changes in lbs. for the 24 subjects who completed the 4-week LOR-mod study arm, which is also depicted in Tables 6-9.
  • Table 10 – Weight Loss or Weight Gain Results of Study No of Subject Screening V7 ⁇ in Weight Weight Subjects No.
  • the combination drug compositions of the present invention should be prescribed by a health provider, preferably the treating physician or nurse practitioner, who will consider any relevant factors, such as the patients' diagnosed condition(s) to be treated, the patients’ age and weight, the patients’ symptoms, the severity of the patients’ symptoms, the drugs and/or drug cocktails of choice to treat the patients’ diagnosed condition(s), the treatment regimens, the dosage strengths, and the chosen routes of administration.
  • a health provider preferably the treating physician or nurse practitioner
  • the present invention also contemplates the safe and effective use of other dosage strengths and treatment regimens not necessarily FDA-approved, i.e., off label use, for the drug compound combinations disclosed herein in accordance with the methods of the present invention when prescribed by a healthcare provider who has taken into careful consideration medical publications, FDA-approved labels, drug monographs, and possible advice from experts supporting such use.

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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne des combinaisons pharmaceutiques comprenant du bupropion et de la trazodone et des procédés d'utilisation de celles-ci pour influer sur la perte de poids chez des sujets qui peuvent être obèses, en surpoids ou souhaitent perdre du poids indésirable ou superflu. La présente invention concerne également des combinaisons pharmaceutiques comprenant du bupropion et de la trazodone et des procédés d'utilisation de celles-ci pour induire une perte de poids, effectuer une gestion de poids, améliorer un trouble sexuel, et/ou améliorer un état de bien-être subjectif faible, médiocre ou inexistant, l'estime de soi et/ou la confiance en soi chez des sujets qui peuvent être obèses, en surpoids ou souhaitent perdre du poids indésirable ou superflu ou qui souhaitent maintenir leur poids. La présente invention concerne également des combinaisons pharmaceutiques comprenant du bupropion et de la trazodone et des procédés d'utilisation de celles-ci pour une gestion de la perte de poids et/ou du maintien du poids.
PCT/US2025/030126 2024-05-21 2025-05-20 Compositions et méthodes pour influer sur la perte de poids, la gestion du poids, les troubles sexuels, le bien-être, l'estime de soi et/ou la confiance en soi Pending WO2025245066A1 (fr)

Applications Claiming Priority (4)

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US202463650042P 2024-05-21 2024-05-21
US202463650164P 2024-05-21 2024-05-21
US63/650,042 2024-05-21
US63/650,164 2024-05-21

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WO2025245066A1 true WO2025245066A1 (fr) 2025-11-27

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PCT/US2025/030126 Pending WO2025245066A1 (fr) 2024-05-21 2025-05-20 Compositions et méthodes pour influer sur la perte de poids, la gestion du poids, les troubles sexuels, le bien-être, l'estime de soi et/ou la confiance en soi
PCT/US2025/030182 Pending WO2025245102A2 (fr) 2024-05-21 2025-05-20 Procédés et compositions pour traiter les troubles sexuels, la perte de poids, le maintien du poids, le bien-être et l'estime de soi

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