[go: up one dir, main page]

US20210015779A1 - Therapeutic compositions and methods - Google Patents

Therapeutic compositions and methods Download PDF

Info

Publication number
US20210015779A1
US20210015779A1 US16/985,072 US202016985072A US2021015779A1 US 20210015779 A1 US20210015779 A1 US 20210015779A1 US 202016985072 A US202016985072 A US 202016985072A US 2021015779 A1 US2021015779 A1 US 2021015779A1
Authority
US
United States
Prior art keywords
sexual
ejaculation
composition
piperylpiperidine
duration
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US16/985,072
Inventor
Bassam Damaj
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Innovus Pharmaceuticals Inc
Original Assignee
Innovus Pharmaceuticals Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Innovus Pharmaceuticals Inc filed Critical Innovus Pharmaceuticals Inc
Priority to US16/985,072 priority Critical patent/US20210015779A1/en
Assigned to INNOVUS PHARMACEUTICALS, INC. reassignment INNOVUS PHARMACEUTICALS, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: DAMAJ, BASSAM
Publication of US20210015779A1 publication Critical patent/US20210015779A1/en
Assigned to ECLIPSE BUSINESS CAPITAL LLC (F/K/A ENCINA BUSINESS CREDIT, LLC), AS AGENT reassignment ECLIPSE BUSINESS CAPITAL LLC (F/K/A ENCINA BUSINESS CREDIT, LLC), AS AGENT SECURITY INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: INNOVUS PHARMACEUTICALS, INC., SEMPRAE LABORATORIES, INC.
Assigned to AVENUE VENTURE OPPORTUNITIES FUND II, L.P. reassignment AVENUE VENTURE OPPORTUNITIES FUND II, L.P. SECURITY INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: INNOVUS PHARMACEUTICALS, INC.
Assigned to INNOVUS PHARMACEUTICALS, INC. reassignment INNOVUS PHARMACEUTICALS, INC. RELEASE BY SECURED PARTY (SEE DOCUMENT FOR DETAILS). Assignors: AVENUE VENTURE OPPORTUNITIES FUND, L.P.
Abandoned legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4415—Pyridoxine, i.e. Vitamin B6
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/443—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A61K33/08—Oxides; Hydroxides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/67—Piperaceae (Pepper family), e.g. Jamaican pepper or kava
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4875—Compounds of unknown constitution, e.g. material from plants or animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular compounds

Definitions

  • the World Health Organization defines Sexual Health as: “ . . . a state of physical, emotional, mental and social well-being in relation to sexuality; it is not merely the absence of disease, dysfunction or infirmity”.
  • PE Premature Ejaculation
  • ears ejaculation also referred to as ‘early ejaculation’ or ‘rapid ejaculation’
  • Premature ejaculation may be defined as ejaculating within one minute or less after sexual intercourse and is the most prevalent sexual dysfunction affecting men across all age groups.
  • PE One in five men in America suffers from PE, mostly affecting men between the ages 18 and 59 years old. The prevalence is estimated at 41%.
  • the two types of PE are: Primary PE: The most common type: Problem present from the beginning of the man's sexual life, and Secondary PE which occurs suddenly at some point in a man's life.
  • PE menejaculate within 1 minute of penetration.
  • the causes of PE include: psychological conditions such as anxiety, depression, overexcitement; and biological effects from drug use, prostate disease, multiples sclerosis, diabetes, inflammation of the prostate and urethra, hormone levels, and low levels of serotonin.
  • PE negatively affects sexual enjoyment and a man's ability to satisfy his partner resulting in:
  • the beneficial effects of the present invention are surprising and unexpected to support and enhance peak sexual performance.
  • a synergistic composition of vitamin B6 (vitamin), magnesium (mineral) and 4 amino acids, the present invention is formulated with two proprietary absorption enhancing ingredients. Regular use of the present invention is well tolerated, gives no drug side effects, and has been clinically evaluated in multiple studies.
  • Applicant has determined that men taking the present invention in the disclosed unit dosage forms report improvements in sexual performance, including increased duration of sexual intercourse, increased satisfaction with sexual intercourse, and improved erectile function.
  • FIG. 1 shows the Ejaculation Sequence of events for Normal Ejaculation (left) and Premature Ejaculation (right).
  • FIG. 2 shows the design of the clinical study testing the present invention.
  • FIG. 3 shows the Mean Duration of Sexual Intercourse experienced by participants in the clinical study as recorded over three visits.
  • FIG. 4 shows Mean Satisfaction with Sexual Intercourse experienced by participants in the clinical study as recorded over three visits.
  • FIG. 5 shows Mean IIEF (International Index of Erectile Function) Sum of Points experienced by participants in the clinical study as recorded over three visits.
  • FIG. 6 shows PEVArxTM labeling indicates:
  • FIG. 7 shows the PEVArxTM Supplement Facts Box:
  • the term “about” has its generally accepted meaning.
  • the term about means ⁇ 10% of the associated value.
  • about 100 mg means 100 mg ⁇ 10 mg.
  • the term about means ⁇ 5% of the associated value.
  • about 100 mg means 100 mg ⁇ 5 mg.
  • the term about means ⁇ 2% of the associated value.
  • about 100 mg means 100 mg ⁇ 2 mg.
  • the term about means ⁇ 1% of the associated value.
  • about 100 mg means 100 mg ⁇ 1 mg.
  • the present invention has been developed as a dietary supplement to support peak sexual performance and stamina.
  • a unit dosage form of the invention may contain one or more pharmaceutical diluents or excipients.
  • a unit dosage form of the invention may comprise microcrystalline cellulose, silicon dioxide, and magnesium stearate.
  • a unit dosage form of the invention comprises one or more excipients selected from hydroxypropyl methylcellulose, rice concentrate, and silica.
  • the amino acids in the present invention includes L-tyrosine, DL-phenylalanine, L-typtophan, L-glutamine, Vitamin B6, magnesium, piperylpiperidine, and an absorption enhancer.
  • L-Tyrosine is a precursor for the synthesis of important biologically active substances, including the Catecholamines (dopamine, adrenaline, noradrenaline) and thyroid hormones. L-Tyrosine may support alertness and regulate stress and moods.
  • DL-phenylalanine is an essential amino acid supporting important biochemical processes in the body by helping the brain develop active chemicals-endorphins, improving mood, increasing the number of receptors to endorphins in the brain, and supporting optimum energy levels.
  • L-tryptophan is an essential amino acid converted into serotonin connection, which contributes to the duration of sexual intercourse and is required for the synthesis of melatonin (regulation of human biorhythms).
  • L-glutamine is required to formulate a number of important vitamins and contributes to efficient muscle growth, ensures nervous activity and maintaining the immune system, and promotes serotonin synthesis, necessary to ensure the normal duration of sexual intercourse.
  • Vitamin B6 (pyridoxine hydrochloride) is required for the synthesis of serotonin which supports the duration of sexual intercourse. Vitamin B6 is also a catalyst for exchange of amino acids and synthesis of neurotransmitters of the central nervous system, resulting in an improved the metabolism in tissues of the brain and a uniform supply of cells to glucose. Vitamin B6 is required for the regulation of (L)-tyrosine.
  • Magnesium in the form of a magnesium salt, such as magnesium oxide, is an important component for the biosynthesis of proteins, as well as for ensuring the processes of excitability and contractility in the nerve elements of muscle tissue. Magnesium is a regulator of the passing of redundant nerve impulses from the brain to peripheral nerves and muscles, prevents excessive spasms (involuntary muscle contractions), including sexual system.
  • Magnesium and vitamin B6 together show a more significant efficiency and at lower doses than when used separately.
  • PEVArxTM contains two natural absorption enhancing ingredients to increase bioavailability:
  • AstraGin® is a patented Absorption Enhancer, and a 100% natural food ingredient derived from highly purified Panax notoginseng and Astragalus mergenaceus . Studies indicate increases in amino acid, vitamin and mineral absorption.
  • Bioperine® is a patented Absorption Enhancer, obtained from black pepper fruits ( Piper nigrum ). Bioperine® helps the body absorb the amino acids (see U.S. Pat. No. 5,536,506 and European Patent EP0810868B1). Bioperine® (extract) inhibits human CYP3A4 and P-glycoprotein enzymes. By inhibiting certain enzymes Bioperine® (extract) may alter the effectiveness of certain medications by increasing bioavailability. Bioperine is Generally Recognized As Safe (GRAS). Bioperine® (CAS Reg. No.
  • 94-62-2 is named as 1-piperylpiperidine; 5-(1,3-benzodioxol-5-yl)-1-(piperidin-1-yl)penta-2,4-dien-1-one; and (2E,4E)-5-(1,3-benzodioxol-5-yl)-1-(piperidin-1-yl)penta-2,4-dien-1-one, and has the structure:
  • Vitamin B6 Mineral Magnesium Amino Acids: L-Tyrosine, DL-Phenylalanine, L-Tryptophan, L-Glutamine Dosing and Administration Adults, 2 capsules/2 times per day with meal Packaging/Storage and 60 capsules per container Handling Store between 20-25 C. (65-77 F.) 3 year shelf life Safety and efficacy Clinically studied and well tolerated Warnings/Caution Intended for adult men Keep out of reach of children Consults with physician before use, especially if hypertensive
  • PEVArxTM Efficacy of PEVArxTM was studied in a pilot, placebo controlled study (2011) in a Population of 43 men with PE, 24-67 years of age (37.9 ⁇ 1.2). The Study duration was 3 months. Results indicated the Duration of sexual intercourse in the treatment group increased on average from 0.9 minute to 3.5 minutes (p ⁇ 0.05) in 67.8% of patients. The efficacy and safety of PEVArxTM was studied in an open label, multicenter study (2013) Population: Men with reported rapid ejaculation. Nine sites reported results of increased length of penetration phase on average by 2.5 times, and improved sexual function as a whole and overall wellbeing.
  • the Data is divided into three groups:
  • PEVArxTM Adverse Events Adverse events related to Adverse events possibly related PEVArx to PEVArx AE N % AE N % Mild allergic reaction 1 0.16 Neuralgia, nausea 4 0.63 Hyperemia 1 0.16 Perinea! discomfort 2 0.32 Drowsiness 3 0.47 Heart rate increases 1 0.16 Dry cough 1 0.16 slightly Total 6 0.95 Total 7 1.1
  • PEVArxTM Clinical Study Results show:
  • FIG. 1 shows the differences in the ejaculation sequence of events for normal ejaculation (left graph) and premature ejaculation (right graph).
  • men suffering from premature ejaculation have a short plateau where the penetration phase occurs.
  • a controlled study of the formula has been shown to increase the length of the penetration phase on average by 2.5 times. By increasing the length of penetration, the plateau shown on the graph lengthens and the sexual experience occurs more like the sequence of events for normal ejaculation (left graph).
  • FIG. 2 shows the clinical study design.
  • the patient is enrolled in the program, the participant fills out an informed consent form (ICF), provides assessment criteria to determine whether the patient can provide useful feedback on the formula, fills out an individual registration card (IRK), and any concomitant therapy is recorded. Further, the participant's Modified International Index of Erectile Function (IIEF) and Hospital Anxiety and Depression Scale (HADS) is measured and recorded for future comparison.
  • ICF informed consent form
  • IIEF Modified International Index of Erectile Function
  • HADS Hospital Anxiety and Depression Scale
  • the patient fills out the individual registration card and the Irk is recorded.
  • the Modified IIEF and HADS of the patient is recorded for comparison with any past and future visits.
  • This clinical trial involved a population of 665 adult men with sexual disorder for a duration of 2 months. Each participant took a dosage of two capsules twice per day for a total of four capsules per day.
  • FIG. 3 shows the mean duration of sexual intercourse for the clinical trial participants.
  • the left graph shows the effect that the formula has on all groups.
  • the average participant had a mean duration of sexual intercourse of 3.3 minutes which increased to 4.9 and 6.5 minutes respectively during additional visits.
  • the average participant experienced an average of 3.0 minutes of sexual intercourse which increased to 4.7 and 6.3 minutes respectively during additional visits.
  • This set of graphs demonstrates that the duration of sexual doubled between the first and third visits for those experiencing premature ejaculation.
  • all participants in the study, including this with and without premature ejaculation reported an average increase of three minutes duration of sexual intercourse between the first and third visits.
  • FIG. 4 shows the mean satisfaction with sexual intercourse experienced by the clinical trial participants.
  • participants from all groups and only the group of participants experiencing premature ejaculation reported the same mean score for all three visits. Both groups reported a mean score of 1.4 during the first visit and the score increased to 2.1 and 3.1 respectively during the following visits for an overall increase of 1.7 from all groups.
  • This set of graphs demonstrates that men taking the recommended dose of the claimed formula experienced over double the satisfaction with sexual intercourse.
  • FIG. 5 shows the mean International Index of Erectile Function (IIEF) sum of points experienced by the clinical trial participants.
  • IIEF International Index of Erectile Function

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Inorganic Chemistry (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Engineering & Computer Science (AREA)
  • Botany (AREA)
  • Organic Chemistry (AREA)
  • Gynecology & Obstetrics (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Zoology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Biotechnology (AREA)
  • Medical Informatics (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention provides compositions and unit dosage forms that are effective to improve sexual performance. Such compositions and unit dosage forms are useful to increase duration of sexual intercourse, satisfaction with sexual intercourse, and improve erectile function in men.

Description

    CROSS REFERENCE TO RELATED APPLICATION
  • This application is a continuation of U.S. patent application Ser. No. 15/829,798, filed Dec. 1, 2017, the entire disclosure of which is incorporated herein by reference.
    • BACKGROUND OF THE INVENTION
  • The World Health Organization defines Sexual Health as: “ . . . a state of physical, emotional, mental and social well-being in relation to sexuality; it is not merely the absence of disease, dysfunction or infirmity”.
  • Common sexual health conditions in men are:
      • Anejaculation—Unable to ejaculate semen
      • Delayed Ejaculation—Difficulty ejaculating
      • Erectile Dysfunction—Inability to achieve or maintain an erection
      • Premature Ejaculation—Ejaculating earlier than desired
      • Retrograde Ejaculation—Semen travels into the bladder during ejaculation
      • Low Testosterone—Inadequate production of testosterone
  • In particular, Premature Ejaculation (PE), also referred to as ‘early ejaculation’ or ‘rapid ejaculation’, is ejaculation with minimal penile stimulation shortly after sexual intercourse or even before intercourse. Premature ejaculation may be defined as ejaculating within one minute or less after sexual intercourse and is the most prevalent sexual dysfunction affecting men across all age groups. One in five men in America suffers from PE, mostly affecting men between the ages 18 and 59 years old. The prevalence is estimated at 41%. The two types of PE are: Primary PE: The most common type: Problem present from the beginning of the man's sexual life, and Secondary PE which occurs suddenly at some point in a man's life. It is estimated that 9 out of 10 men ejaculate within 1 minute of penetration. The causes of PE include: psychological conditions such as anxiety, depression, overexcitement; and biological effects from drug use, prostate disease, multiples sclerosis, diabetes, inflammation of the prostate and urethra, hormone levels, and low levels of serotonin.
  • PE negatively affects sexual enjoyment and a man's ability to satisfy his partner resulting in:
      • Low self-esteem
      • Frustration and depression
      • Withdrawal leading to a strenuous relationship
      • Loss of interest in sex
        One out of every three men feel that they ejaculate too soon and wish they could increase the length of arousal before ejaculation. A need exists for safe and effective supplements to treat such sexual health conditions.
    SUMMARY OF THE INVENTION
  • The beneficial effects of the present invention are surprising and unexpected to support and enhance peak sexual performance. A synergistic composition of vitamin B6 (vitamin), magnesium (mineral) and 4 amino acids, the present invention is formulated with two proprietary absorption enhancing ingredients. Regular use of the present invention is well tolerated, gives no drug side effects, and has been clinically evaluated in multiple studies.
  • Applicant has determined that men taking the present invention in the disclosed unit dosage forms report improvements in sexual performance, including increased duration of sexual intercourse, increased satisfaction with sexual intercourse, and improved erectile function.
    • BRIEF DESCRIPTION OF THE FIGURES
  • FIG. 1 shows the Ejaculation Sequence of events for Normal Ejaculation (left) and Premature Ejaculation (right).
  • FIG. 2 shows the design of the clinical study testing the present invention.
  • FIG. 3 shows the Mean Duration of Sexual Intercourse experienced by participants in the clinical study as recorded over three visits.
  • FIG. 4 shows Mean Satisfaction with Sexual Intercourse experienced by participants in the clinical study as recorded over three visits.
  • FIG. 5 shows Mean IIEF (International Index of Erectile Function) Sum of Points experienced by participants in the clinical study as recorded over three visits.
  • FIG. 6 shows PEVArx™ labeling indicates:
      • Support longer sexual performance
      • Supported by clinical trials
      • Synergistic formulation to support sexual performance
      • Daily support
      • Increased absorption
      • Well tolerated
  • FIG. 7 shows the PEVArx™ Supplement Facts Box:
      • One month supply
      • Synergistic vitamin and mineral combination
      • Four amino acids to support longer sexual performance
      • Two patented absorption enhancers: AstraGin® and Bioperine®
     DETAILED DESCRIPTION
  • As used herein, the term “about” has its generally accepted meaning. In one embodiment, the term about means±10% of the associated value. For example, about 100 mg means 100 mg±10 mg. In one embodiment, the term about means±5% of the associated value. For example, about 100 mg means 100 mg±5 mg. In one embodiment, the term about means±2% of the associated value. For example, about 100 mg means 100 mg±2 mg. In one embodiment, the term about means±1% of the associated value. For example, about 100 mg means 100 mg±1 mg.
  • The present invention has been developed as a dietary supplement to support peak sexual performance and stamina.
  • In one embodiment, a unit dosage form of the invention may contain one or more pharmaceutical diluents or excipients. For example, in one embodiment a unit dosage form of the invention may comprise microcrystalline cellulose, silicon dioxide, and magnesium stearate. In another embodiment a unit dosage form of the invention comprises one or more excipients selected from hydroxypropyl methylcellulose, rice concentrate, and silica.
  • The amino acids in the present invention includes L-tyrosine, DL-phenylalanine, L-typtophan, L-glutamine, Vitamin B6, magnesium, piperylpiperidine, and an absorption enhancer. L-Tyrosine is a precursor for the synthesis of important biologically active substances, including the Catecholamines (dopamine, adrenaline, noradrenaline) and thyroid hormones. L-Tyrosine may support alertness and regulate stress and moods.
  • DL-phenylalanine is an essential amino acid supporting important biochemical processes in the body by helping the brain develop active chemicals-endorphins, improving mood, increasing the number of receptors to endorphins in the brain, and supporting optimum energy levels.
  • L-tryptophan is an essential amino acid converted into serotonin connection, which contributes to the duration of sexual intercourse and is required for the synthesis of melatonin (regulation of human biorhythms).
  • L-glutamine is required to formulate a number of important vitamins and contributes to efficient muscle growth, ensures nervous activity and maintaining the immune system, and promotes serotonin synthesis, necessary to ensure the normal duration of sexual intercourse.
  • Vitamin B6 (pyridoxine hydrochloride) is required for the synthesis of serotonin which supports the duration of sexual intercourse. Vitamin B6 is also a catalyst for exchange of amino acids and synthesis of neurotransmitters of the central nervous system, resulting in an improved the metabolism in tissues of the brain and a uniform supply of cells to glucose. Vitamin B6 is required for the regulation of (L)-tyrosine.
  • Magnesium in the form of a magnesium salt, such as magnesium oxide, is an important component for the biosynthesis of proteins, as well as for ensuring the processes of excitability and contractility in the nerve elements of muscle tissue. Magnesium is a regulator of the passing of redundant nerve impulses from the brain to peripheral nerves and muscles, prevents excessive spasms (involuntary muscle contractions), including sexual system.
  • Magnesium and vitamin B6 together show a more significant efficiency and at lower doses than when used separately.
  • PEVArx™ contains two natural absorption enhancing ingredients to increase bioavailability:
  • AstraGin® is a patented Absorption Enhancer, and a 100% natural food ingredient derived from highly purified Panax notoginseng and Astragalus membrenaceus. Studies indicate increases in amino acid, vitamin and mineral absorption.
  • Bioperine® is a patented Absorption Enhancer, obtained from black pepper fruits (Piper nigrum). Bioperine® helps the body absorb the amino acids (see U.S. Pat. No. 5,536,506 and European Patent EP0810868B1). Bioperine® (extract) inhibits human CYP3A4 and P-glycoprotein enzymes. By inhibiting certain enzymes Bioperine® (extract) may alter the effectiveness of certain medications by increasing bioavailability. Bioperine is Generally Recognized As Safe (GRAS). Bioperine® (CAS Reg. No. 94-62-2) is named as 1-piperylpiperidine; 5-(1,3-benzodioxol-5-yl)-1-(piperidin-1-yl)penta-2,4-dien-1-one; and (2E,4E)-5-(1,3-benzodioxol-5-yl)-1-(piperidin-1-yl)penta-2,4-dien-1-one, and has the structure:
  • Figure US20210015779A1-20210121-C00001
  • Studies indicate absorption of nutrients are enhanced by at least 30% with PEVArx™
  • TABLE 1
    PEVArx ™ Product Profile
    Use Support sexual performance and duration
    Composition Vitamin B6
    Mineral: Magnesium
    Amino Acids: L-Tyrosine, DL-Phenylalanine,
    L-Tryptophan, L-Glutamine
    Dosing and Administration Adults, 2 capsules/2 times per day with meal
    Packaging/Storage and 60 capsules per container
    Handling Store between 20-25 C. (65-77 F.)
    3 year shelf life
    Safety and efficacy Clinically studied and well tolerated
    Warnings/Caution Intended for adult men
    Keep out of reach of children
    Consults with physician before use, especially
    if hypertensive
  • Efficacy of PEVArx™ was studied in a pilot, placebo controlled study (2011) in a Population of 43 men with PE, 24-67 years of age (37.9±1.2). The Study duration was 3 months. Results indicated the Duration of sexual intercourse in the treatment group increased on average from 0.9 minute to 3.5 minutes (p<0.05) in 67.8% of patients. The efficacy and safety of PEVArx™ was studied in an open label, multicenter study (2013) Population: Men with reported rapid ejaculation. Nine sites reported results of increased length of penetration phase on average by 2.5 times, and improved sexual function as a whole and overall wellbeing.
  • PEVArx™ Clinical Study: The efficacy and safety of PEVArx™ was studied in a multicenter, non-interventional (observational) study in men with sexual dysfunction. Population: 665 men with sexual dysfunction (analysis on 630 patients). Clinical sites: 23 centers. Duration: 2 months. Study design: Observational. Study article: PEVArx™—two (2) capsules taken twice daily (oral). Inclusion: Sexual dysfunction (PE ED, anxiety, erosion of orgasm). Exclusion: Contraindication for study article, acute psychiatric symptoms.
  • Measurement tools:
      • Individual registration card (IRK)
      • Concomitant therapy information
      • Hospital anxiety and depression scale (HADS)
      • Modified IIEF to measure ejaculatory function
  • Analysis of the PEVArx™ Clinical Study Data
  • The Data is divided into three groups:
      • Group 1: PE (rapid ejaculation) Self-reported (N=582/92.4%)
      • Group 2: Orgasmic disorder (N=17/2.7%)
      • Group 3: Urologic disease (inflammatory disease of the prostate, ED, BPH etc.) secondary to anxiety (N=31/4.9%)
  • Evaluation of PEVArx™ effectiveness:
  • Duration of penetration phase of sexual contact time was evaluated on the grading scale:
      • Pronounced effect: ≥50% increase in duration
      • Good effect 30-49% increase in duration
      • Satisfactory effect: 10-29% increase duration
      • An unsatisfactory effect: absence of positive dynamics of the patient or the patient's degradation
  • Data Analysis PEVArx™ Effectiveness on Duration: Effectiveness of treatment in patients during penetration phase of sexual contact (duration time) showed the following in Tables 2 and 3.
  • TABLE 2
    All groups
    Visit 2 Visit 3
    Grade (n) % (n) % (p)2-3
    Pronounced 358 60.6 470 81.0 0.00
    Good 54 9.1 34 5.9 0.052
    Satisfactory 35 5.9 19 3.3 0.014
    Unsatisfactory 144 24.4 57 9.8 0.00
    Total 591 580
  • TABLE 3
    Group 1: PE Patients
    Visit
    2 Visit 3
    Grade (n) % (n) % (p)2-3
    Pronounced 344 61.9 451 82.8 0.00
    Good 50 9.0 32 5.9 0.06
    Satisfactory 34 6.1 16 2.9 0.017
    Unsatisfactory 128 23.0 46 8.4 0.00
    Total 556 545
  • TABLE 4
    PEVArx ™ Adverse Events
    Adverse events related to Adverse events possibly related
    PEVArx to PEVArx
    AE N % AE N %
    Mild allergic reaction 1 0.16 Neuralgia, nausea 4 0.63
    Hyperemia 1 0.16 Perinea! discomfort 2 0.32
    Drowsiness 3 0.47 Heart rate increases 1 0.16
    Dry cough 1 0.16 slightly
    Total 6 0.95 Total 7 1.1

    In summary, PEVArx™ Clinical Study Results show:
    • Efficacy
      • Penetration duration: 91.6% of patients in Group 1 (PE population) reported an increase on average of 2.5 times at end of study
      • Overall patient satisfaction: On average, 3 times increase in all groups
      • IIEF domains: Statistically significant improvement of sexual function of patients on virtually all domains
      • Anxiety-depressive symptoms: Decrease on symptoms HADS (Hospital Anxiety and Depression score) in 90% of the patients.
      • Concomitant medications: A notable decline in continued use of other medicines and dietary supplements (Group 1 decreased from 21.9% to 12.7% by end of study)
    Safety
      • Well tolerated both alone and in combination with other drugs
  • All publications, patents, and patent documents are incorporated by reference herein, as though individually incorporated by reference. The invention has been described with reference to various specific and preferred embodiments and techniques. However, it should be understood that many variations and modifications may be made while remaining within the spirit and scope of the invention.
  • FIG. 1 shows the differences in the ejaculation sequence of events for normal ejaculation (left graph) and premature ejaculation (right graph). As evidenced by the difference between the two graphs, men suffering from premature ejaculation have a short plateau where the penetration phase occurs. A controlled study of the formula has been shown to increase the length of the penetration phase on average by 2.5 times. By increasing the length of penetration, the plateau shown on the graph lengthens and the sexual experience occurs more like the sequence of events for normal ejaculation (left graph).
  • FIG. 2 shows the clinical study design. During the first visit, the patient is enrolled in the program, the participant fills out an informed consent form (ICF), provides assessment criteria to determine whether the patient can provide useful feedback on the formula, fills out an individual registration card (IRK), and any concomitant therapy is recorded. Further, the participant's Modified International Index of Erectile Function (IIEF) and Hospital Anxiety and Depression Scale (HADS) is measured and recorded for future comparison. During the first visit the study article is dispensed for the patient's own personal information about the formula.
  • During the second and third visits, the patient fills out the individual registration card and the Irk is recorded. The Modified IIEF and HADS of the patient is recorded for comparison with any past and future visits. This clinical trial involved a population of 665 adult men with sexual disorder for a duration of 2 months. Each participant took a dosage of two capsules twice per day for a total of four capsules per day.
  • FIG. 3 shows the mean duration of sexual intercourse for the clinical trial participants. The left graph shows the effect that the formula has on all groups. During the first visit, the average participant had a mean duration of sexual intercourse of 3.3 minutes which increased to 4.9 and 6.5 minutes respectively during additional visits. For participants experiencing premature ejaculation, the average participant experienced an average of 3.0 minutes of sexual intercourse which increased to 4.7 and 6.3 minutes respectively during additional visits. This set of graphs demonstrates that the duration of sexual doubled between the first and third visits for those experiencing premature ejaculation. Furthermore, all participants in the study, including this with and without premature ejaculation, reported an average increase of three minutes duration of sexual intercourse between the first and third visits.
  • FIG. 4 shows the mean satisfaction with sexual intercourse experienced by the clinical trial participants. For this measurement, participants from all groups and only the group of participants experiencing premature ejaculation reported the same mean score for all three visits. Both groups reported a mean score of 1.4 during the first visit and the score increased to 2.1 and 3.1 respectively during the following visits for an overall increase of 1.7 from all groups. This set of graphs demonstrates that men taking the recommended dose of the claimed formula experienced over double the satisfaction with sexual intercourse.
  • FIG. 5 shows the mean International Index of Erectile Function (IIEF) sum of points experienced by the clinical trial participants. For this measurement, participants from all groups and the group of participants experiencing premature ejaculation reported the same mean score for all three visits. Both groups reported a mean score of 27.1 for the first visit and the score increased to 32.9 and 39.4 respectively during subsequent visits. As a result, this set of graphs demonstrates that both the total group of participants and those participants experiencing premature ejaculation experienced a mean total increase of 12.3 points on the IIEF scale between the first and third visits.

Claims (17)

1-12. (canceled)
13. A method of treating a sexual health condition, comprising:
administering a composition comprising:
vitamin B6,
magnesium oxide,
L-tyrosine,
DL-phenylalanine,
L-tryptophan,
L-glutamine, and
1-piperylpiperidine;
to a subject in need thereof.
14. The method of claim 1, wherein the composition further comprises an absorption enhancer derived from Panax notoginseng and Astragalus membrenaceus.
15. The method of claim 1, wherein the composition further comprises one or more excipients selected from the group consisting of hydroxypropyl methylcellulose, rice concentrate, and silica.
16. The method of claim 1, wherein the composition is administered orally.
17. The method of claim 15, wherein the composition is formulated in a capsule dosage form.
18. The method of claim 1, wherein the composition comprises:
about 800 μg vitamin B6;
about 8 mg Mg2+ from magnesium oxide;
about 400 mg L-tyrosine;
about 400 mg DL-phenylalanine;
about 100 mg L-tryptophan;
about 52 mg L-glutamine; and
about 20 mg 1-piperylpiperidine.
19. The method of claim 18, wherein the composition further comprises an absorption enhancer derived from Panax notoginseng and Astragalus membrenaceus.
20. The method of claim 1, wherein the 1-piperylpiperidine is synthetically produced.
21. The method of claim 1, wherein the 1-piperylpiperidine is an extract from the fruit of a plant in the genus Piper.
22. The method of claim 17, wherein two capsules are administered bid.
23. The method of claim 22, wherein the capsules are administered with a meal.
24. The method of claim 1, wherein the sexual health condition is selected from the group consisting of anejaculation, delayed ejaculation, erectile dysfunction, premature ejaculation, retrograde ejaculation, low testosterone, premature ejaculation, orgasmic disorder, and urologic disorder.
25. The method of claim 24, wherein duration of sexual intercourse is increased.
26. The method of claim 24, wherein satisfaction with sexual intercourse is increased.
27. The method of claim 24, wherein erectile function is improved.
28. The method of claim 25, wherein ejaculatory function is improved.
US16/985,072 2017-12-01 2020-08-04 Therapeutic compositions and methods Abandoned US20210015779A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US16/985,072 US20210015779A1 (en) 2017-12-01 2020-08-04 Therapeutic compositions and methods

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US15/829,798 US10758505B2 (en) 2017-12-01 2017-12-01 Therapeutic compositions and methods
US16/985,072 US20210015779A1 (en) 2017-12-01 2020-08-04 Therapeutic compositions and methods

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US15/829,798 Continuation US10758505B2 (en) 2017-12-01 2017-12-01 Therapeutic compositions and methods

Publications (1)

Publication Number Publication Date
US20210015779A1 true US20210015779A1 (en) 2021-01-21

Family

ID=66657461

Family Applications (2)

Application Number Title Priority Date Filing Date
US15/829,798 Expired - Fee Related US10758505B2 (en) 2017-12-01 2017-12-01 Therapeutic compositions and methods
US16/985,072 Abandoned US20210015779A1 (en) 2017-12-01 2020-08-04 Therapeutic compositions and methods

Family Applications Before (1)

Application Number Title Priority Date Filing Date
US15/829,798 Expired - Fee Related US10758505B2 (en) 2017-12-01 2017-12-01 Therapeutic compositions and methods

Country Status (2)

Country Link
US (2) US10758505B2 (en)
CA (1) CA3026043A1 (en)

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5744161A (en) * 1995-02-24 1998-04-28 Sabinsa Corporation Use of piperine as a bioavailability enhancer
US5536506A (en) 1995-02-24 1996-07-16 Sabinsa Corporation Use of piperine to increase the bioavailability of nutritional compounds
US20010008641A1 (en) * 1998-11-25 2001-07-19 R. Douglas Krotzer Nutritionally active composition for bodybuilding
CA2523831C (en) 2003-04-29 2008-11-18 Pfizer Inc. 5,7-diaminopyrazolo[4,3-d]pyrimidines useful in the treatment of hypertension
US20090143433A1 (en) 2004-12-01 2009-06-04 Curt Hendrix Cocktail for modulation of alzheimer's disease
US20080305096A1 (en) * 2007-06-07 2008-12-11 Unicity International, Inc. Method and composition for providing controlled delivery of biologically active substances
US20090197892A1 (en) 2007-08-21 2009-08-06 Nawaz Ahmad Anhydrous compositions useful for attaining enhanced sexual wellness
US8846061B1 (en) 2011-03-08 2014-09-30 Mark S. Bezzek Multivitamin-mineral regimens for longevity and wellness
CA2925318C (en) 2013-09-27 2021-01-19 Justin SHER Nutraceutical composition for pde4 inhibition, enhanced dopamine metabolism and long term potentiation
CA2963569A1 (en) 2013-11-04 2015-05-07 Atp Institute Pty Ltd Vasodilator formulation and method of use
FR3027228B1 (en) 2014-10-20 2016-12-09 Valbiotis COMPOSITION COMPRISING A MIXTURE OF PLANT EXTRACTS AND USE FOR ACTING ON GLUCIDIC AND / OR LIPID METABOLISM
EP3621617A1 (en) 2017-05-12 2020-03-18 Innovus Pharmaceuticals, Inc. Therapeutic methods and compositions

Also Published As

Publication number Publication date
US20190167620A1 (en) 2019-06-06
CA3026043A1 (en) 2019-06-01
US10758505B2 (en) 2020-09-01

Similar Documents

Publication Publication Date Title
Ioannides-Demos et al. Pharmacotherapy for obesity
US9700548B2 (en) Antihistamines combined with dietary supplements for improved health
US20100189819A1 (en) Neuro-degenerative inhibitor, neuro-endocrine modulator, and neuro-cerebral metabolism enhancer
US11033543B2 (en) Methods of providing weight loss therapy in patients with major depression
CN115811955A (en) Paraxanthine-based bioactive compositions and methods of use thereof
US20090137565A1 (en) Method for treatment of movement disorders
TWI583390B (en) Ellagitannins rich extracts composition
US20220133741A1 (en) AAntihistamines In Combination With A Range Of Substances For Improved Health
US6759437B2 (en) Comprehensive pharmacologic therapy for treatment of obesity including cysteine
CN110996987A (en) Compositions and methods for modulating hormonal cascades in stress disorders
Kingsberg et al. Evaluation of flibanserin safety: comparison with other serotonergic medications
US20210015779A1 (en) Therapeutic compositions and methods
KR102693607B1 (en) Treatment for restless legs syndrome
US11766458B2 (en) Method and a dietary composition on regulation, treatment, and prevention of obesity
US20180055849A1 (en) Nutraceutical capsule and tablet formulations providing enhanced mental clarity, concentration and stamina while minimizing adrenaline and dopamine concentration perturbations associated with withdrawal
EP1347778B1 (en) Behavior chemotherapy
US20120231098A1 (en) Weight loss composition
US9610285B2 (en) Compositions for controlling food intake and uses therefor
US20240284941A1 (en) Antihistamines combined with dietary supplements for improved health
AU2001218105A1 (en) Behavior chemotherapy
US20180243251A1 (en) Composition and Method for Improving Cognitive Function
EP1742639A2 (en) Use of selective chloride channel modulators to treat alcohol and/or stimulant substance abuse
Sao et al. Targeted Therapies in Obesity Management
Wurtman Ramelteon: a melatonin receptor agonist
English Protecting Your Brain From The Damaging Effects of Modern Stress and Anxiety

Legal Events

Date Code Title Description
AS Assignment

Owner name: INNOVUS PHARMACEUTICALS, INC., CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:DAMAJ, BASSAM;REEL/FRAME:054054/0586

Effective date: 20180122

STPP Information on status: patent application and granting procedure in general

Free format text: APPLICATION DISPATCHED FROM PREEXAM, NOT YET DOCKETED

STPP Information on status: patent application and granting procedure in general

Free format text: DOCKETED NEW CASE - READY FOR EXAMINATION

AS Assignment

Owner name: ECLIPSE BUSINESS CAPITAL LLC (F/K/A ENCINA BUSINESS CREDIT, LLC), AS AGENT, ILLINOIS

Free format text: SECURITY INTEREST;ASSIGNORS:INNOVUS PHARMACEUTICALS, INC.;SEMPRAE LABORATORIES, INC.;REEL/FRAME:058789/0001

Effective date: 20220126

AS Assignment

Owner name: AVENUE VENTURE OPPORTUNITIES FUND II, L.P., NEW YORK

Free format text: SECURITY INTEREST;ASSIGNOR:INNOVUS PHARMACEUTICALS, INC.;REEL/FRAME:058976/0706

Effective date: 20220101

STPP Information on status: patent application and granting procedure in general

Free format text: NON FINAL ACTION MAILED

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION

AS Assignment

Owner name: INNOVUS PHARMACEUTICALS, INC., NEW YORK

Free format text: RELEASE BY SECURED PARTY;ASSIGNOR:AVENUE VENTURE OPPORTUNITIES FUND, L.P.;REEL/FRAME:067728/0206

Effective date: 20240612