BR102017025256A2 - MINOXIDIL ASSOCIATED WITH VARIOUS DRUGS AND USE OF OXYTOCIN FOR THE TREATMENT OF FEMALE AND MALE FEMALE DYSFUNCTIONS - Google Patents

Abstract

minoxidil associated with various drugs and use of oxytocin to treat female and male sexual dysfunction. The present patent application relates to the claim of development of new pharmaceutical products for treating various female and male sexual dysfunctions. they are drug associations with minoxidil and various forms of presentations. The associated drugs are: (dhea) dehydroepiandrosterone; estradiol; testosterone; phenylalanine; melatonin; bromocriptine; apomorphine; pergolide; prostaglandins - pg 1; sildenafil; tadalafil; vardenafil; yohimbine; bragging; b endorphin; oxytocin alone and in combination with minoxidil, minoxidil alone or in combination. use for clinical treatment of various sexual dysfunctions, such as: alterations of desire, stimulation, orgasmic dysfunctions, dyspareunias and vaginismus; psychogenic impotence, erectile dysfunction, premature ejaculation, delayed ejaculation, hypo-sexuality, hyperssexuality, reduced vaginal lubrication, anor- gmia, women's orgasmic difficulty and vaginismus. Presentations are claimed: cream, gel, solution, vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets, compressed tablets. oral, sublingual spray, transdermal and intradermal, injectables and v injectables im and injectable im scheduled release. indications for patients with one or more concomitant sexual dysfunction.

Description

DESCRIPTIVE REPORT

MINOXIDIL ASSOCIATED WITH SEVERAL DRUGS AND USE OF OXYTOCIN TO TREAT FEMALE AND MALE SEXUAL DYSFUNCTIONS.

[001] - This patent application refers to the development of new pharmaceutical products for the treatment of various female and male sexual disorders. Several types of drug presentations are also part of this patent application, for these new drugs claimed.

[002] - This patent aims to claim the use of the substance minoxidil in various concentrations, for use alone or associated with several other drugs, also claiming the use of the substance OXYTOCINA, in ISOLATED form in specific concentrations and in the condition of OXYTOCIN ASSOCIATED WITH THE MINOXIDIL SUBSTANCE, for the treatment of several sexual dysfunctions, IN BOTH SEXES.

[003] - The concentrations of MINOXIDIL that are part of this patent are CHARACTERIZED FOR BEING (0.01% to 30%) and may be associated with other drugs and MINOXIDIL CHARACTERIZED FOR BEING IN ISOLATED FORM in concentrations of (0.01% to 0.09%) and (10.1% to 30%) all of which are indicated for the treatment of MALE AND FEMALE sexual dysfunctions.

[004] - As for the general aspects of sexual dysfunctions, we know that sexual dysfunctions that affect humans,

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2/80 in both men and women are the DYSFUNCTIONS OF THE PHASE OF DESIRE, STIMULUS,

ORGASTIC DYSFUNCTIONS, DISPAREUNIAS AND VAGINISM.

[005] - To solve these sexual difficulties in the Human Being, we are proposing, through this patent, the invention of NEW DRUGS, through DRUG ASSOCIATIONS AND IN DIFFERENT CONCENTRATIONS, with DIVERSE AND WIDE PRESENTATION WAYS, the majority being for genital and local use , to cover and benefit a larger number of patients, as well as to determine a greater range of sexual pathologies to be treated, from a medical-scientific-pharmacological point of view, in both sexes.

[006] - STATE OF THE TECHNIQUE - There is a state of the art in which the patent was issued for O MINOXIL OF ISOLATED FORM, in the concentration of (0.1 to 10%) and NOT IN ASSOCIATION, indicated for erectile dysfunction in diabetic patients with vascular changes and NORMAL MEN WITH SEXUAL DEFICIT, according to the following data: US

005336678A- PATENT NUMBER = 5, 336, 675 DATE: 08.09.1994 - TITLE: USE OF MINOXIDIL FOR TREATMENT OF ERECTILE IMPOTENCE - INVENTOR: GIORGIO CAVAILINI VIA MONTEBELO, 49 - FERRARA - ITALY. A METHOD OF TREATMENT OF HUMAN ERECTILE IMPOTENCY BY TOPICAL ADMINISTRATION TO THE PENIS OF TOPIC OF COMPOSITION CONTAINING (0.1% TO 10) OF MINOXIDIL.

[007] - This Patent Application, consists of MINOXIDIL IN THE DIFFERENT CONCENTRATION FROM (0.01% TO 0.09%) AND

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3/80 (10.1% to 30%) IN ITS ISOLATED FORM, AND, IN ASSOCIATION WITH OTHER SUBSTANCES, in concentrations of (0.01% to 30%), WHICH DIFFERENTS FROM THE STATE OF THE TECHNIQUE.

[008] - The advantages, benefits and differences in relation to the state of the art are as follows:

[009] - Indications - THE CLINICAL INDICATIONS will be for the TREATMENT OF MALE AND FEMALE SEXUAL DYSFUNCTIONS, while the state of the art, in addition to the concentration being different, presentations, as the state of the art recommends a single male sexual dysfunction - erectile dysfunction - in diabetic patient and with vascular changes, another aspect that guides this patent is to be characterized in DRUG ASSOCIATIONS WITH VARIOUS OTHER SUBSTANCES.

[010 - Our association and concentrations are different from the state of the art, allowing a greater range of the number of pathologies to be benefited in men and women, including several sexual dysfunctions.

[011] - It also benefits with the associations, the drug treatment of erectile dysfunction in men who are not responsive to the dosages of the state of the art and can improve sexual performance in so-called normal men, that is, without basic pathology present, as well as, in patients with psychogenic impotence, erectile dysfunction associated with premature ejaculation, dysfunction of desire, reduced vaginal lubrication, women in menopause or not,

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4/80 anorgasmia, orgasmic difficulty for women, changes in the phase of sexual arousal, vaginismus and dyspareunias.

[012] - Regarding drug presentations, the differential aspects of novelty, innovation and industrial applicability present in this patent are the fact that we are claiming ALL THE PRESENTATION FORMS listed below, which may or may not be used and used for a given product or no, depending on clinical, market, commercial and industrial interest. We are claiming the presentations to know, for all the drugs claimed in this patent application, such as: cream, gel, solution, vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, programmed-release tablets, oral tablets, sublingual spray, transdermal and intradermal, IV injectables, IM injectables and IM injectables.

[013] - Claims for this patent are associations of the substance minoxidil, in concentrations of (0.01% to 30%) with various other drugs and minoxidil in concentrations of (0.01% to 0.09%) in a way isolated and minoxidil in concentrations of (10.1 to 30%) in isolation, as well as Oxytocin in Isolated or in combination, all for the treatment of various male and female sexual dysfunctions. Another important aspect is the fact that despite the different concentrations, different types of presentations, despite almost all being presented

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5/80 topical doses for genital use, these new drugs are indicated in general, for the universe of sexual dysfunctions in both sexes. Such characteristics have a character of innovation, novelty and may be produced industrially, in association or independently.

[014] - The drugs that are part of this patent are: (DHEA) DEHIDROEPIANDROSTERONE (0.1 MG A150 MG); MlNOXIDIL (0.01 to 0.09%); MINOXIDIL (0.01% TO 30% in ASSOCIATION), MINOXIDIL (10.1% TO 30%); estradiol (in the forms of 17b estradiol, benzoate, phenylpropionate) IN THE CONCENTRATIONS OF (0.01 MG - 10 MG); TESTOSTERONE (in the forms of caproate; esters, propionate and undecanoate) IN THE CONCENTRATIONS VARIANT FROM (0.01 MG TO 1000 MG), PHENYLALANINE (0.1 MG / DL TO 5.0 MG / DL); MELATONIN (0.1 MG TO 60 MG); BROMOCRIPTIN (0.01 MG TO 100 MG); APOMORFIN (0.1 MG TO 20 MG); PERGOLIDE (0.01 MG TO 10 MG); PROSTAGLANDINE - PG 1 (0.1 MCG TO 500 MCG); SILDENAFILA (0.1 MG TO 500MG); TADALAFILA (0.1 MG TO 200MG); VARDENAFILA (0.1 MG TO 200MG); IOIMBINA (0.1 MG TO 50 MG); GABA IN THE CONCENTRATIONS OF (0.01 MG TO 600MG) AND GABA IN THE CONCENTRATIONS OF (850MG TO 1500 MG); B-ENDORPHINE (0.1% TO 30%); OXYTOCIN IN ISOLATED FORM IN THE CONCENTRATIONS OF (0.01 IU TO 3 IU); OXYTOCIN IN ISOLATED FORM IN THE CONCENTRATIONS OF (6UI TO 50 IU); OXYTOCIN IN THE CONCENTRATIONS OF (0.01 IU TO 50 IU) ASSOCIATED WITH MINOXIDIL IN THE CONCENTRATION OF (0.01% TO 30%) [015] - As we weave the Universe of Clinical Sexology, since the beginning of the sexual revolution, in the 60s and with the

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6/80 With the birth of the birth control pill, human sexuality has been demanding from science, pharmaceutical industries and society, definitions, solutions and resolution of their sexual dysfunctions, which affect men, since its origin; on the other hand, the human male society continues without much concern for sexual life. With the advent of AIDS, and, in the face of this new global situation, “the man returns home” and “in bed” his problems and sexual dysfunctions become evident, appearing for his steady partner, in a significant and viceverse way.

[016] - In this way, the incidence of sexual dysfunctions both male and female has a frightening increase, never before detected; which now need to be treated, however, there are practically NO DRUGS, MAINLY FOR THE PUBLIC OF FEMALE GENDER.

[017] - Currently, there are some drugs for erectile dysfunction, however, almost all of them lack medicines that can benefit women, worldwide, who have a high rate of sexual dysfunction, and it is possible to estimate a high incidence on two billion women of sexually active age in menacme worldwide.

[018] - We know that the incidence of premature ejaculation can reach 72.72% in men, whose work functions are highly stressful (NASCIMENTO, EDSON C., 2001 - XV ^th WORLD CONGRESS OF SEXOLOGY - PARIS - 2001) erectile dysfunction reaching 28% (NASCIMENTO, EDSON C., 2001 -XV ^th WORLD CONGRESS OF SEXOLOGY - PARIS Petition 870180073364, of 21/08/2018, page 21/99

7/80

2001) and women's orgastic changes = 45.27% (NASCIMENTO, EDSON C., 2001 -XV * WORLD CONGRESS OF SEXOLOGY-PARIS-2001).

[019] - Changes in sexual function can present with high incidence, at different times in life, and can affect both men and women.

[020 - Several authors have contributed to the study of physiology, pharmacology and more in-depth research in the development of neuro-pharmacological, neurochemical actions and even within the scope of neuroscience and behavior and sexual pharmacology (NASCIMENTO, EDSON, C, 1996) . It aims to propose new solutions for the treatment of sexual dysfunctions; from the psycho-emotional aspects to the psycho-social-sexual and behavioral aspects.

[021] - Several authors have investigated these aspects, such as: SCHWERDTNER J, SOMMER M, WEBER T, MÜLLER J. KARCZMAR AG. JONES HB. GIRALDI AG, VICTOR J .; CESK GYNEKOL; JUN ;. CZECH .; MOLL JL, BROWN, C. S .; SIMON, J. A .; STAHL, S.M.; TRAISH, A.M; BOTCHEVAR, E .; KIM, N.N .; LABRIE, F .; ARCHER, D.F .; BOUCHARD, C .; FORTIER, M .; CUSAN, L .; GOMEZ, J.L .; GI-RARD, G .; BARON, M .; AYOTTE, N .; MOREAU, M .; DUBÉ, R .; CÔTÉ, I .; LABRIE, C.; LAVOIE, L .; BERGER, L .; GILBERT, L .; MARTEL, C.

BALSER, J .; PANZICA, G.C., GARCÍA-OJEDA, E., VIGLIETTIPANZICA, C., ASTE, N .; OTTINGER, M.A .; HULL, E.M .; LORRAIN, D.S .; DU, J .; MATUSZEWICH, L .; LUMLEY, L.A .;

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PUTNAM, S.K .; MOSES, J .; KLEITZ-NELSON, H.K .; DOMINGUEZ, J.M .; BALL, G.F .; GORDON, J.H .; NANCE, D.M .; WALLIS, C.J .; GORSKI, R.A .; ROSEN, M.I .; KOSTEN, T.R .; KREEK,

M.J .; TORII, M .; KUBO, K; SASAKI, T .; FERNÁNDEZGUASTI, A .; VEGA-MATUSZCZYK, J .; LARSSON, K .; SEGRAVES, R.T .; CROFT, H .; KAVOUSSI, R .; ASCHER, J.A .; BATEY, S.R .; FOSTER, V.J .; BOLDEN-WATSON, C .; METZ, A; NASCIMENTO, EDSON, C .; OF BIRTH, E.C.

[022] - 1) SEXUAL DESIRE PHASE: The sexual desire phase consists of producing the perception of the sensation of psychosexual interest, which may come from the fantasies of having some sexual activity, through images or bodily sensations about the sexual act and the desire to perform an act whose physical discharge is through the genitals, as well as the psychic, on a psycho-mental level.

[023] - 2) SEXUAL EXCITATION PHASE: The sexual arousal phase depends on a satisfactory history of previous sexual relations; bodily stimuli and excitatory cognitive as well as inhibitory aspects. It is when sexual stimulation, whether physical, psychic, emotional or mental or even pharmacological, can determine neuronal influx to the hypothalamic limbic system, basically regions of the IV ventricle, para-hippocampal area, cingulate gyrus, nipple bodies, and many others associative areas directly and indirectly, and for the genital regions, determining neurochemical changes, at the central and peripheral level, as well as changes in the shape, lubrication and sensitivity of the genitals.

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9/80 [024] - 3) ORGASTIC PHASE: Corresponds to the changes that may occur at the peak of sexual pleasure, producing neurochemical, organic, psycho-mental and emotional changes. It is the time of sexual fullness.

[025] - 4) RESOLUTION PHASE: Occurs after the orgasmic phase, usually in a pleasurable sexual act, in which a generalized muscle relaxation appears, with the sensation of sexual satisfaction. Below we will mention the dysfunctions of the sexual desire phase:

[026] - HYPOSEXUALITY or also known as HYPOACTIVE DESIRE - When there is a reduction in sexual interest in the partner or a reduction in sexual frequency.

[027], It affects both men and women, however, in the female public, nowadays, it is the most common dysfunction. The decrease in desire is perceived by the person affected as a lack of interest in the search for the partner, reduced sexual desire, decreased performance of sexual acts, even repulsion of the partner as an exciting individual, not looking for the partner, non-correspondence the voluntary interest in having a sexual act, no physiological response to the production of erection or vaginal lubrication or even the lack of sexual disposition towards a partner or other sexual partners. Anxiety, chronic depression, betrayal, other cognitive, hormonal, nosological factors, etc .; in short, all these factors can be causes of the reduction of sexual desire. Such a situation can occur from adolescence to senility. It occurs between 15 - 45% of people.

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10/80 [028] - This patent seeks to produce some drugs that can increase libido, sexual performance, as well as sexual frequency and orgasmic capacity, in both sexes. [029] - a) HYPERSSEXUALITY - The pattern of

Hypersexuality is the opposite of Hyposexuality. It is when there is an intense need to satisfy the sexual drive. There is an increase in sexual interest, with the same partner (o) or with other people, including strangers, and also reaching sexual promiscuity, as occurs in cases of patients with manic bipolar disorder. It affects both sexes. Hypersexuality within a pattern of sexual adequacy among partners is normal and there is no need for treatment; however, when a sudden or unusual increase occurs, it may reflect some pathology, both hormonal and psychiatric. There are clinical cases of increased need to satisfy this drive, which can become social problems, including police connotations, etc. In the psychiatric condition, from the old manic depression, known today with a more appropriate name, bipolar disorder is one of them. In bipolar disorder we have two basic phases; a depressive pattern and a euphoric or so-called manic pattern. In the case of the euphoria phase, there are cases in which the patient may present a picture of hypersexuality, with significant negative social damage, emitting highly inappropriate sexual behaviors, reaching sexual promiscuity, at different times and in different social environments.

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11/80 [030] - b) SEXUAL AVERSION: it is defined as complete avoidance of any genital sexual contact with a partner. Usually cognitive aspects can contribute to these disorders such as: shame, betrayal, guilt, hurts, traumatic experiences in the past, etc. In this type of dysfunction, an inhibitory mechanism of sexual disposition occurs. However, currently studies show that some neurochemical changes, producing psycho-behavioral changes, such as the lack of psychic intimacy with the partner, some aspects related to affectivity and cognitive aspects can contribute to this dysfunction.

[031] - The effects of neurotransmitters on sexual behavior have long been known, according to several scientific works by some authors, such as Meyerson, B.J .; Jones, H.B; among many others.

[032] -. Some drugs can alter sexual desire and other sexual functions, such as ADT - TRICYCLIC ANTIDEPRESSANTS, SSRIs - SELECTIVE SEROTONIN RECAPTATION INHIBITORS, BENZODIAZEPHINES, ANTICONVULSIVES, BETA-BLOCKERS, SOME ANTI-HYPERTENSIVE CLOTHES AND MEDICINES

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12/80 [033] - SEXUAL EXCITATION PHASE DYSFUNCTIONS - In women it is characterized by the partial or total absence of vaginal lubrication; it is a physiological and pathophysiological mechanism analogous to male erection. The opposite can also happen, with the person having a HYPERLUBRICATION, and many people INTERPRET this as FEMALE EJACULATION, it becomes MISTER to explain that the WOMAN DOES NOT EJACULA, this is a specific urological term of semen emission from the seminal vesicle and the woman it contains no seminal vesicle, prostate or testicles. Therefore, it is a term only used for man. WOMAN DOES NOT EJACULA! What happens is that some women, at the orgasmic moment, produce intense relaxation, including in the sphincter of the female urethra and the release of urine occurs, which can often mix with the vaginal transudate and being interpreted with ejaculation squirt.

[034] - HYPEXEXITATION - In the case of hypoexcitation one of the consequences is the inability to keep the sexual act satisfactory until the end or due to the absence or both mechanical and psychological failure of sexual excitation; what in men is equivalent to penile erection and in women is intra-vaginal lubrication; often, it is the genesis of female dyspareunia (pain during sex) due to lack of lubrication or vaginal dryness.

[035] - It is common to have a shortage of vaginal transudate that lubricates the vaginal canal that prepares to receive the penis during sexual intercourse; in these cases, it occurs in up to 30% of women, due to lack of sexual arousal or hypoactive desire. In WOMEN IN THE MENOPAUSE STAGE, the incidence of this dysfunction makes

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13/80 if much higher. The general cause can be hypoestrogenism, neurotransmitters, hormones or even psychosocial factors, such as, strongly repressive education, previously destructive sexual experience, among other cognitive factors.

[036] - ERETIVE DISORDER: ERECTILE DYSFUNCTION Formerly known as Sexual Impotence, today this term is no longer used, due to the name Sexual Impotence being very generic, covering all sexual dysfunctions and not defining the specific pathology itself. It can occur in a more rare way in the beginning of sexual life, being more frequent to appear such dysfunction, throughout the life of the man. The highest frequency occurs from 40 - 50 years old or being situational, when coincidentally, there is also a decline in testosterone production. Younger men tend to have less erection changes than older men, and when it occurs in young people, there is usually a psychogenic etiology. The causes in general can be organic or psychogenic. Erectile dysfunctions of organic causes are due to a medical condition that can alter blood flow to the vasavasorum capillaries, capillaries, vessels, arteries and penile arterioles, in patients with long-standing diabetic mellitus, around 20 years of diabetes poorly controlled mellitus, diabetic neuropathy can occur, where it can also be a serious and often serious cause of sexual dysfunction. In these cases, they are often resolved with the use of penile prostheses. Common medicines from the medical clinic, can be the cause and when replaced by others, they can improve performance, decrease the level of tests

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14/80 serum tosterone, changes in neurotransmitters, long-standing diabetes mellitus, poorly controlled or in the case of psychological causes may have different cognitive etiologies. It occurs from an inability to have a full erection, to an erection that is not maintained during intercourse or a partial erection that does not allow the penis to be introduced into the vagina. In Definition Erectile Dysfunction is the inability to keep the penis erect until intra-vaginal penetration. Nascimento, Edson C, defined at the World Congress of Sexology in Paris, that when penetration occurs almost immediately, ejaculation occurs, it is no longer Erectile Dysfunction, but Premature Ejaculation, even when you lose your erection after penetration without ejaculation can be a partial or total dysfunction. Not necessarily, but it can go along with the dysfunction of desire. Mostly, the patient has sexual desire, however, he does not have the ability to maintain the erection until penetration, which characterizes erectile dysfunction or formerly known as sexual impotence.

[037] - In MANY CASES, patients report that despite PRESENTING ERECTION, THEY ARE NOT SATISFIED WITH THE DEGREE OF PENIS ENRICHMENT, and this patent will contemplate this type of dysfunction that affects men also, in men, said to be normal.

[038] - This patent recommends some drugs to improve this clinical situation as well, as this group of patients needs to be treated pharmacologically.

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15/80 [039] - Some drugs may contribute to the production of this sexual dysfunction, such as: tricyclic antidepressants, selective serotonin reuptake inhibitors, lithium carbonate, antipsychotics, some antihypertensive drugs in the brain and some other drugs used in the daily medical clinic.

[040] - ORGASTIC PHASE DYSFUNCTION - ORGASTIC DISORDER - It is more common in women, being also defined by some authors as recurrent orgasm inhibition, or ANORGASMIA. This author defines it differently (NASCIMENTO, EDSON, C. 2001) calling it ORGASTIC DIFFICULTY OF WOMEN, differentiating it from ANORGASMIA. Because in the woman's Difficulty Organs there is usually a great sexual excitement and with an immense difficulty in reaching sexual climax. Depending on the degree of manipulation, excitement and the partner, the woman may or may not reach sexual climax. However, she may have an orgasm.

[041] - ANORGASMIA is manifested by the absence of orgasm during a sexual act, penile penetration, in which there was previously a satisfactory excitation phase. Currently, more frequent complaints are observed in women who are in the stage of the orgasmic plateau, in a high degree of excitability, and, failing to develop the action potential necessary to trigger orgasm, as they do not reach the optimal threshold for orgasm. For this situation, the etiological mechanism is not yet established. The author and applicant for this patent Edson Claro Do Nascimento (Nascimento, Edson. C.) has been very concerned with this issue, and has been scientifically inquiring if it is due to lack of concentrations

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16/80 neurochemicals of some neurotransmitter, excess of inhibitory neurotransmitter, high metabolism of some neuromodulators necessary to elicit neural transmission, etc. which can produce ideal concentrations to develop the action potential in neurons, at the level of the hypothalamic limbic system, to produce the optimal threshold and peak orgasm or other factors. It is when the woman is in a high degree of arousal and has great difficulty to have orgasm. However, depending on the type of stimulus, the time this stimulus is applied and the quality of the sexual stimulus, the affectivity and sexual interaction itself, with the person, confidence with the sexual partner and even sexual intimacy, etc. , this woman may or may not have an orgasm. This is a situation in which Nascimento, EC, differentiates between the orgasmic difficulty of women and anorgasmia, as he considers that ANORGASMIA IS WHEN THE WOMAN CANNOT ACHIEVE ORGASTIC FULLNESS IN ANY WAY, as is the case of some pituitary tumors , and, in contrast, in the case that is much more frequent, the ORGASTIC DIFFICULTY OF THE WOMAN, WHICH SHE MAY OR NOT, REACH THE SEXUAL CLIMATE, on some occasions and on others not, despite the great sexual effort and even a lot of desire and high degree of sexual arousal that she can experience at this sexual moment.

[042] - In this situation depending on the partner's sexual stimulation, the partner's stimulation time, itself; the woman can often reach orgasm.

[043] - In TRUE ANORGASMY the woman does not reach orgasm in any way, as already said.

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17/80 [044] - This dysfunction is also being studied with great scientific attention; due to these possible neurochemical changes, where the concentration of neurotransmitters and brain biochemical aspects are inhibiting or modulating, in an unsatisfactory way, the physiology in the hypothalamic limbic sexual system.

[045] - Some drugs can cause changes in the regulation or dysregulation of the biological clock in the orgastic phase, both in men and women, such as tricyclic antidepressants, selective serotonin reuptake inhibitors, antipsychotics, among others.

[046] - EARLY EJACULATION = It is the most common male sexual dysfunction in men, reaching a frequency of 72% of men, in work functions, important from the point of view of stress. (DO NASCIMENTO, EDSON, C .; 2001 - WORLD CONGRESS OF SEXOLOGY PARIS - FRANCE).

[047] - EARLY EJACULATION HAS NEUROCHEMICAL ETIOLOGY REDUCING THE CONCENTRATION OF 5-HT, in the synaptic clefts of the hypothalamic limbic system and even in the peripheral nervous system (FROM BIRTH, EC 2001 - XIV ™ WORLD CONGRESS OF SEXOLOGY-PARIS- 2001).

[048] - It is characterized by intra-vaginal ejaculation long before the partner's orgasm, or, of the partners, in MOST sexual intercourse. Normally, men ejaculate long before female orgasm in most of their sexual relationships. It is a myth

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18/80 the fact that the man has to have an orgasm at the same time as the woman. There is no need for this, the important thing is that it is, in a condition that the woman has pleasure, preferably first, the man being able to be soon after or moments later.

[049] - Therefore, REDUCING THE CONCENTRATION OF SEROTONIN (5HT) in the synaptic clefts of the hypothalamic limbic system and at the peripheral level is THE CAUSE OF EARLY EJACULATION (NASCIMENTO, E.C, 1996 - PARIS - FRANCE).

[050] - Other sexual dysfunctions can also be present in isolation or associated with other sexual dysfunctions, in the same human being in both men and women, and can be in up to 10 different sexual dysfunctions, in the same person.

[051] - DYSPAREUNIA: It is characterized by pain or discomfort during sexual intercourse. It is much more frequent in females, however, it can occur in both men and women, and can be caused by nosological factors, such as gynecological pathologies, surgical procedures or prostatitis or even psychological causes, changes in the stimulus with consequent lack of vaginal lubrication are also frequent etiologies. It may be accompanied by several organic causes that must be investigated or even psychogenic. TRUE SEXUAL DYSPAREUNIA, Edson Claro do Nascimento, defines it as something psychic, THAT DOES NOT contain a pathologically organic etiological agent.

[052] - VAGINISM: It is the involuntary contraction of the lower third of the vagina, hinders the penetration of the penis and may reach

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19/80 a more serious situation to prevent the penetration of the penis itself. This dysfunction is much more frequent in clinical practice, than its frequency is reported in the medical literature.

[053] - It is known that according to the work of Prosex HCFMUSP, some aspects contribute to sexual performance, such as feeling and affection, which are significant in 77.2% for women and 62.3% for men; the degree of intimacy between the couple was 70.6% for women and 63.9% for men; the appropriate climate and environment were 70.5% for women and 63.6% for men; physical attraction was 68.2% for women and 73.5% for men; enough time and tranquility was 66.5% for women and 69.5% for men. (Data from the Sexuality Project Study (Prosex-USP). The data described above demonstrates that several other external factors, which interfere in the organic cerebral and peripheral environment, through external stimuli, fantasies, thoughts and physical-social and behavioral aspects, become a brain biochemical-pharmacological language, which can interfere with the biochemical and pharmacological aspects of sexuality.

[054] - Below will be presented some of the substances that present activity in the sexual universe, either exciting, inhibiting or modulating, increasing irrigation in the genital region, or modulating neuronal synapses, acting as prohormones, inhibiting excitatory synapses, in the condition of excitatory neurotransmitters, in short, improving sexual performance through various physiological and neurochemical forms

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20/80 human, which, some of them, are part of this patent application.

[055] - Some drugs that participate directly or indirectly, exciting, inhibiting or modulating synapses will be presented, that is, they act in some way in the physiology of human sexual behavior, whether psychic, organic or both, simultaneously.

[056] - MINOXIDIL - MINOXIL is a vasodilator drug initially used to treat severe arterial hypertension. It was synthesized in 1963 by the Upjohn-Michigan laboratories and it was observed that patients on chronic use of this drug, orally, developed hypertrichosis. In 1980, Zappacosta reported hair removal in a patient with androgenic alopecia, using Minoxil by mouth, an observation that has also been reported by other authors. In 1985, it was established that 2% is the lowest concentration of topical solution capable of bringing the desired therapeutic effects, without affecting blood pressure, and it was released for the treatment of ANDROGENIC ALOPECIA in 1987. The cutaneous absorption of minoxidil ( 2.4 diamino-6-pipe-ridino-pyridimine-3-oxide) is low, about 1.4% of the applied dose. Franz studied twelve male adults, using a 1 and 5% minoxidil solution, marked with carbon 14 and observed, in these individuals, a low urinary excretion of radioactivity (1.6 to 3.9%), no fecal elimination and permanence of drug, at the skin level, around 41 to 45% of the applied dose. The mean blood levels with local use of 1.2 and 5% minoxidil were 1.1 ng / ml, 1.7 ng / ml and 2.8 ng / ml, respectively. To give you an idea, when used orally, the average blood levels with 2.5 mg of

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21/80 minoxidil are 32.8 ng / ml and, with 5 mg, they are 59.2 ng / ml. Storer et al. suggest constant absorption with the use of the drug, based on blood levels, which do not change over time for a year. Use in concentrations of 1 to 2% in less than 50% of the scalp is relatively safe, with systemic effects unlikely. Repeated applications do not result in greater absorption of the drug, unless used eight times a day. There appears to be skin saturation for a period of time after the initial dose. Minoxidil is metabolized to minoxidil sulfate, which has greater pharmacological action. This metabolism in the hair follicle, by the activity of a sulfotransferase, which is greater in the hair follicle than in the epidermis and dermis.

[057] - Due to its vasodilating action in genital regions, such, where there are no hair follicles, such as:

GLAND, CLITORIS, PENIS BODY, SMALL LIPS, INTRÓITO VULVAR, ETC, BIRTH, E. C. recommends this patent application for use for topical application in these regions, aiming at the resolution and improving the FEMALE AND MALE SEXUAL DYSFUNCTIONS. Being absorbed by the capillaries “vasavasorum” of the penis, it produces an increase in the influx of blood to the corpora cavernosa of the penis and clitoris and the labia majora, thus determining penile and clitoral erection, which is important to determine at this moment that it DIFFERS FROM THE STATE OF THE TECHNIQUE, which exists for ONLY DIABETIC MEN WITH VASCULAR CHANGES AND IN THE PERCENTAGE OF 10% MINOXIDIL, while this Patent, claims DIFFERENT CONCENTRATIONS, for NORMAL MEN WHO WANT TO IMPROVE SEXUAL PERFORMANCE, or those

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22/80 which the state of the art concentration is not pharmacologically sufficient for the clinical effect. In the case of WOMEN with sexual dysfunctions, mainly anorgasmia, orgasmic difficulty for women, dyspareunias, reduced libido, due to vasodilation, increases clitoral and labia volume and by a mechanical mechanism with greater possibility of friction of the penis, in these areas, there is an increase in the frequency of the influx of neural stimuli to the genital region and S1, S2 of the spinal cord, taking such stimuli through the Spino-Talamic Córtico Tract to the limbic areas of the CNS, increasing the release of neurotransmitters, thus allowing , increase the threshold of action potential in these regions, contributing to the triggering of the optimal action potential for orgasm to occur. [058 As for the clitoris, the influx also occurs to the cavernous body of the clitoris and other regions of the vulvar introitus, large and small lips, producing an increase in the clitoris and through even a mechanical process, there is an increase in clitoral friction in the body of the penis, which leads to a greater influx of nerve stimuli to spinal cord neurons in S1, S2, S3, S4, thus producing a greater degree of neuronal stimulus, through the Cortico-Spino-Talamic Tract, to the areas of the Hypothalamic Limbic System, producing a broader action potential, thus determining a better orgastic response for women. Due to an antagonistic form, due to vasodilation, it may reduce the diameter of the vaginal introitus during the phases of excitation, plateau and orgasm, also increasing penile friction by a mechanical effect, increasing the influx of stimuli

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23/80 neuronal to the hypothalamic limbic system, producing a PSYCHORGANIC orgasm, which is a total orgasm (Nascimento, EC1998) or an ORGANIC ORGASM (NASCIMENTO, E C., 1998) in which the nerve stimuli go to the spinal cord, they make a reflex arc and return to the target organ, respectively, which in this case is the genital, whether male or female, while in the PSYCO-ORGANIC ORGASM, the neuronal influxes enter the TALAMIC CORK SPINE TRACT, producing TOTAL OR ALMOST TOTAL DEPOLARIZATION in different areas of the brain.

[059] - We know that there is a shortage, practically total, of medicines for the female public, destined for female sexual dysfunctions, in our pharmacological-industrial universe. [060] The request for this PI refers to the presentation of minoxidil (10.1% to 30%) and the use of minoxidil (0.01% to 30%) ASSOCIATED with several other substances in different concentrations and specific presentations, which will be developed industrially, according to the needs of the market and clinical practice.

[061] - Therefore, in view of these actions, we claim for the following clinical indications of women and men, regarding changes in the phases: sexual desire phase, sexual arousal phase and in the orgastic phase, dyspareunia.

[062] - In the case of male patients who obtained refractory responses with lower concentrations of (0.1 to 10%) may obtain a satisfactory clinical response, with minoxidil in higher concentrations of minoxidil (10.1 to 30%) , how

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24/80 is the case with this patent application, which differs from the state of the art.

[063] - These medications can be applied in several ways: one to two hours before sexual intercourse or once a day, daily; as in the case of diabetic people, which leads to an increase in vascular permeability, generating a greater influx of blood to the cavernous bodies of the penis, but with different concentrations, from the state of the art; being used two to three times a week, depending on the clinical indication. It can be used specifically, one hour before sexual intercourse, depending on each case and the clinical indication, for both men and women, with the advantage of a much better sexual elicitation.

[064 For both men and women; LOCAL drug administration may produce vasodilatory pharmacological action in the penile and vaginal region, determining vasodilation and facilitating erection, both penile and clitoral, by increasing the influx of blood through the vasavasorum capillaries, sinusoidal and helical capillaries of the corpora cavernosa, with the consequence the increase in the diameter of the penis body and enlargement of the glans and clitoris, as well as, in the vaginal opening, large and small lips, with the advantage of better accommodating the penis at the time of penetration and increased sexual sensitivity, by the woman, as well as, of man.

[065] - This produces penile stiffness, due to the fact that it increases blood flow to a certain anatomical area,

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25/80 in the case, the penis and vaginal, minoxidil can improve sexual performance in both sexes.

[066] - Therefore, the objective of this patent is also to claim the use of minoxidil to increase sexual performance in men and women - normal - without associated previous pathology.

[067] - This improves the state of penile stiffness and increases sexual stimulation and arousal in women, who already have an erection or stimulation, but are not satisfactory enough, for the patient, according to their own assessment of the physical, psychic or psychological view.

[068] - It is also claimed for application in men with sexual dysfunctions of various etiologies, not only, erectile dysfunction in patients with diabetes mellitus and vascular insufficiency, as is the case of the state of the art, of minoxidil, in the concentration (0.1 to 10%).

[069] - It is also indicated for psychological erectile dysfunction, which has a good clinical response.

[070] - Can be applied with the penis in an erect or flaccid state.

[071] - Therefore, the MEDICINES ASSOCIATION has the advantage of benefiting a huge portion of both the male and female population, solving the majority of sexual dysfunctions in humans, for the treatment of male and female sexual dysfunctions, according to clinical indication and clinical picture.

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26/80 [072] - The pathophysiology of sexual dysfunctions both male and female are very similar.

[073] - The local application in the region of the glans and the body of the penis and in the woman, in the clitoral region, large and small lips and introitus vagina are in thin layer and is devoid of unpleasant and harmful effects.

[074] - These aspects give this patent claim the character of innovation, novelty and industrial applicability, since they present drug associations as different concentrations of minoxidil and with different presentations, method of use, applications and dosage for the use of the substance minoxidil, state of the art.

[075 - We know that the global pharmacological market needs more specific drugs for the area of sexual health.

[076] - It is then imperative to invent these new drugs for drug treatment, aiming at the clinical improvement of these sexual dysfunctions, such as, in the case of male sexual dysfunctions: erectile dysfunction, premature ejaculation, delayed ejaculation, male dyspareunia, changes in desire, changes in stimulation, as well as female sexual dysfunctions, such as: orgastic difficulty, changes in stimulation and changes in woman's desire.

[077] - OXYTOCINA - The substance OXYTOCINA or Oxytocin, the most used name = OXYTOCINA. It is a hormone produced by the hypothalamus and stored in the posterior pituitary

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27/80 (neurohypophysis) and initially has the function of promoting uterine muscle contractions during childbirth and the ejection of milk during breastfeeding.

[078] - However, currently, there are other functions in the medical literature worldwide, from REDUCING STRESS, reducing the release of cortisol at the moment of sexual stimulation and orgasm, making tranquility and REDUCING SEXUAL ANXIETY, happen in the moments of sexual activity, both in the psycho - behavioral point of view, as affective and neurochemical.

[079] - HAS AN IMPORTANT ACTIVITY IN THE STIMULUS AND ORGASTIC EXCITEMENT PHASES. The activation of the anterior insular and cingular cortex and the para-ventricular nucleus was observed as a precursor to the production of oxytocin in the hypothalamus and its consequent release by the posterior pituitary. This hormone is responsible for the sensation of pleasure. Several experts call it the love hormone. Like Prolactin, the concentration of OXYTOCIN is increased by 40% after orgasm. OXYTOCINA besides causing rhythmic contractions of the uterus, oxytocin contracts the myoepithelial cells that surround the breast alveoli. With the manipulation of the nipples, as well as other erogenous regions of the human body, there is an increase in the concentration of oxytocin at the level of the hypothalamic limbic system. These effects are very interesting from a sexual point of view. Another function that oxytocin produces in the sexual response is, above all, to facilitate attraction and tactile sensation, with increasing levels to the touch and spikes (spiking) in the phase of stimuli, love games and

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28/80 even during orgasm. In this way, we can also explain the importance of love games, especially for women, where in each touch there is an increase in the concentration of released oxytocin and causes this to increase the intimacy and ease of orgasm, between sexual partners, both male and female. female. OCYITOCINA inhibits the release of stress hormones: the glucocorticoid. It is released by the Ventro-Mediai Nucleus of the Hypothalamus (NVMH) at the moment of sexual stimulation and orgasm; inhibiting stress hormones at the sexual moment, ABOLE STRESS AT THE MOMENT OF ORGASM, as well as, also in man, making tranquility appear in the sexual situation and facilitating the ejaculatory procedure, the occurrence of orgasm and the sexual excitement. There is a possibility that the reduction or the difficulty of the individual in the body to produce ideal concentrations of this neurotransmitter, may be responsible for the sexual difficulty in the phases of arousal, ejaculatory and orgasmic, in both sexes. Clinical complaints of women who report a high degree of pre-orgasmic excitability and fail to develop orgasm, it is believed that one of the causes may be a low concentration of oxytocin, at the level of the hypothalamic limbic system and or their actions at the peripheral level. direct or indirect through neurotransmitters, neuromodulators, in short, an adaptation in the neurochemical content of the CNS or

Peripheral.

[080] - Other actions of oxytocin, which several researchers have observed is its action in psycho - behavioral and affective situations, of great importance in the relationship

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Human sexual 29/80; such as, the interaction between partners, with regard to the increase of sexual intimacy, trust and even in monogamous behavior, where it was observed that oxytocin in adequate concentrations, favors this psychosocial behavior among humans.

[081] - OXYTOCINA is also responsible for inertia and the post-orgasm period, also known as the absolute refractory period; which time is much longer in men than in women. In this period there is a total lack of interest in a new sexual stimulus, drowsiness, intense muscular relaxation, psychic feeling of tranquility. Relaxation and drowsiness are directly proportional to the release of oxytocin concentration and the psychic satisfaction of orgasm. This sensation occurs when the orgasm is highly effective and satisfying. The association of oxytocin to minoxidil can greatly improve sexual dysfunctions of women, men and women, in the phases of desire, stimulation and excitation, orgasm and resolution. In conclusion, it is known that oxytocin is increased in the pre-orgasmic phase, during orgasm and immediately after orgasm, considering that it, by itself, plays a highly relevant role in the genesis of the orgasmic mechanism, both in men and women. in women. This alone authorizes us to state that oxytocin plays an important role in human sexual satisfaction and that sex is essential for human health. It actually abolishes stress organically, psychically and mentally.

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30/80 [082] - There is the state of the art in relation to the active ingredient of Syntocinon nasal spray, in isolation or injectable form, for obstetric use, which is a synthetic nonapeptide identical to oxytocin, a hormone released by the posterior lobe of pituitary gland, other than oxytocin. However, our claim differs from the state of the art, basically, in concentrations and associations.

[083] - DIFFERENCES FROM THE STATE OF THE TECHNIQUE - CLINICAL INDICATION - The state of the art recommends for obstetric use, while this patent recommends for the treatment of sexual dysfunctions, in both sexes.

[084] - CONCENTRATIONS - The concentrations of oxytocin in isolation recommended in this patent are broader and can be applied, with better safety for patients, according to the clinical response.

[085] - It is known today that oxytocin has a role in the moment of excitation, plateau phases, orgasmic moment and orgasmic powders.

[086] - There are several studies, where they verify the beneficial and active participation of oxytocin in human sexual behavior, as well as, in animals, cited by several authors, such as: Helen Wills, 2010; Baskerville Ta, Douglas Aj .; Schumacher M; Coirini H; Pfaff Dw; Mcewen; Pedersen Ca; Boccia Ml, Orts, A. Avila, J. Esplugues, J.Brugger A .; Suzor R; Juret P., Polimarchetti P; Legros M; Nascimento, E.C., among several other works.

[087] - TESTOSTERONE - Testosterone is an androgen that has a sexual excitatory role at the peripheral level,

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31/80 also produced physiologically in both sexes. It is the hormone of excellence for libido in both sexes, in peripheral terms. The testosterone used for these combinations can be performed in any of the following ways: caproate; esters, propionate and undecanoate.

[088] - DHT - DIHIDROTESTOSTERONE - DIHIDROTESTOSTERONE (DHT) is the most potent androgen produced in men and women. It is considered 2-3 times more potent than testosterone. DHT binds to specific receptors with more affinity and specificity than other androgens. Although 20 - 25% of circulating DHT in men are derived from direct secretion in the testicles, it is considered to be a predominant product of peripheral formation in both men and women. DHT can be formed in various non-endocrine tissues, but it is primarily formed in the skin and sexual tissues such as the prostate and the skin of the female genitalia. The DHT production rate is approximately 300 pg / day in men and 25 - 55 pg / day in women.

[089] - DHT is formed from testosterone or androstenedione. Testosterone is the main circulating androgen precursor of DHT in men, DHT is formed directly from testosterone, via the enzyme 5 @ -reductase. In women, the primary precursor of DHT in the circulation is androstenedione. Studies show that androstenedione accounts for approximately 60% and testosterone for only 15% of total DHT production; the remainder is derived from DEHIDROEPIANDROSTERONE, 5-androstene-3 "and 17" -diol. The formation of DHT from

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32/80 of androstenedione in women occurs in two different ways, the most important of which involves the conversion of androstenedione to 5 @ -androstana-3, 20-dione by the action of 5 @ -reductase and subsequent conversion to DHT through the action of 17 @ -hydroxysteroid oxide - reductase. The other route of DHT formation involves the conversion of androstenedione to testosterone via the 17 @ -hydroxysteroid oxidoreductase enzyme, and the subsequent conversion of testosterone to DHT as previously described. Plasma levels of DHT vary during the lifetime of both women and men. In normal women, DHT levels before puberty are very low (<30 pg / ml), during the years leading up to menopause the levels are between 50 and 300 pg / ml. After the onset of menopause, DHT levels generally decline, returning to pre-puberty levels. In men, pre-puberty DHT levels are less than 100 pg / ml, with an interval between 250 to 750 pg / ml in adulthood. Most of the circulating DHT is linked to the SHBG. This plasma protein has about 3 times more affinity for testosterone and 9 times more affinity for estradiol. A considerable proportion of DHT also circulates bound to albumin and about 1% circulates in the free form. There is also a sexual difference in the proportion of DHT linked to SHBG AND ALBUMIN. The percentage of circulating DHT linked to SHBG and albumin is 60% and 39% in men, to 78% and 21% in women, respectively. DHT goes through a reduction and conjugation process. It is reduced primarily to 5 "androstan-3, 17" diol (3 "-androstenediol) via enzyme 3" hydroxysteroid oxidizer

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33/80 ductase. Likewise, a small proportion of DHT is converted to 3 @ -androstenediol. In the sequence, the androstenediol isomers 3 "and 3" initiate conjugation. In recent years, attention has focused on the 3 @ androstenediol glucuronide, which has been shown to be an important marker of the activity of the 5 @ -reductase enzyme and the peripheral action of androgens. Other products of DHT metabolism include its conjugated form, called DHT glucuronide and DHT sulfate.

[090] - Both testosterone and DI-HYDROTESTOSTERONE produce sexual arousal in men and women. We know that since the use of the hormone testosterone, as its precursors and derivatives, directly or indirectly, have positive activity and influence on sexual behavior, correcting various sexual dysfunctions, of the phases of desire, excitement and orgasms, such as low libido, hypoactive desire, stimulation alteration, orgastic dysfunction secondary to these dysfunctions, dyspareunia due to lack of lubrication and stimulus, hypogonadism, sexual dysfunction secondary to the climacteric, both male and female. The testosterones that are in the STATE OF THE TECHNIQUE are in injectable presentations, compressed, but in different concentrations and not associated with minoxidil or estrogens, according to the application of this patent. Taking into account the forms of presentations, which are not only injectable for intramuscular use, nor administered in isolation, orally, such as some state of the art, already existing, for example, Durateston, Androxon, Estandron P, existing on the market . There are several forms of testosterone

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34/80 such as caproate, isocaproate, esters, propionate; undecanoate, etc. Which belong to the state of the art, however, NONE OF THEM IS ASSOCIATED WITH MINOXIDIL.

[091 - ESTRADIOL - 17 BETA ESTRADIOL - THE ASSOCIATIONS OF ESTRADIOL in concentrations of (0.1 mg to 15 mg) ASSOCIATED with TESTOSTERONE in the concentration of (0.1 mg to 1000 mg) and MINOXIDIL (0.01 to 30% ) recommended in this patent, does not belong to the state of the art.

[092] - ASSOCIATIONS OF: (DHEA) DEHYDROEPIANDROSTERONE (0.1 mg to 1000 mg) ASSOCIATED WITH MINOXIDIL in concentrations of (0.01 to 30%); ASSOCIATED WITH ESTRADIOL (0.1 mg - 15 mg) also do not belong to the state of the art, and can be produced according to the clinical-scientific and market interest, under several other presentations.

[093] - There are several scientific studies that support the use of androgens, to improve sexual performance in men and women, such as: De Wylie K; Rees M; Hackett G; Anderson R; Bouloux Pm; Cust M; Goldmeier D; Kell P; Terry T; Trinick T; Wu F; Labrie F; Archer Df; Bouchard C; Fortier M; Cusan L; Gomez Jl; Girard G; Baron M; Ayotte N; Moreau M; Dubé R; Côté I; Labrie C; Lavoie L; Berger L; Gilbert L; Martel C; Balser J; Guay A; Traish A; Panzica Gc, García-Ojeda E, Viglietti-Panzica C, Aste N, Ottinger Ma .; Simon Ja .; Põllãnen E. Sipilã S, Alen M. Ronkainen H, Ankarberglindgren C, Puolakka J, Suominen H, Hamanããenen E, Turpeinen U.Konttinen Yt.Kovanen V; Brotto La.Petkau Aj, Labrie F. Basson R; Derogatis Lr; Matsuda K, Sakamoto H, Kawata M .; Coolen Lm, Hull Em .; Pardridge Wm, Gorski Ra, Lippe Bm, Green

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35/80

R .; Panzica Gc, García-Ojeda E, Viglietti-Panzica C, Aste N, Ottinger Ma .; Schober Jm, Pfaff D .; Gladk; Labrie F; Archer Df; Bouchard C; Fortier M; Cusan L; Gomez Jl; Girard G; Baron M; Ayotte N; Moreau M; Dubé R; Côté I; Labrie C; Lavoie L; Berger L; Gilbert L; Martel C; Balser J); Guay A; Traish A Traish Am; Botchevar E; Kim Nn; Wylie K; Rees M; Hackett G; Anderson R; Bouloux Pm; Cust M; Goldmeier D; Kell P; Terry T; Trinick T; Wu F); Ej; Barnett Mj; Tenerowicz Mj; Kim Ja; Wei H; Perry Pj.

[094] - ESTRADIOL - ESTRADIOL must be used in several forms, such as: BENZOATE, PHENYLPROPIONATE AND 17 B-ESTRADIOL.

[095] - Estrogens are part of a group of hormones which have an important participation, also in female sexuality, regarding the dysfunctions of desire, in the participation of the orgasmic phase and in vaginal lubrication, mainly, in the female climacteric.

[096] - MONOAMINES - MONOAMINES are biochemical substances derived from amino acids due to the decarboxylation process. The main monoamines are AS

CATECO LAMINAS (DOPAMINE, NOREPINEFRINA, EPINEFRINA) originated from tyrosine; tryptamine-derived serotonin and histamine from histidine. Monoamines act in the human body as neurotransmitters, NOREPINEFRINE, SEROTONIN AND DOPAMINE being the most abundant in the nervous system. We know of the participation of catecholamines as an intense and significant stimulant of monoa

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36/80 mines, catecholamines and their derivatives in human sexual health as well as, their derivatives, directly or indirectly, in human sexual behavior, regarding motivation, hypoactive desires, elicitation of sexual stimulation, participation in the complex mechanism of orgasm, etc. . There is no state of the art in these conditions, and it can be produced according to the clinical-scientific and market interest, as well as, derived from catecholamines, such as Pergolide, etc. In various forms of presentation.

[097] - Several researchers have presented scientific works, with wide different views of the actions of these neurotransmitters, such as: Larson Et; Norris Do; Gordon Grade E; Summers Ch Holder Mk, Hadjimarkou Mm, Zup SI, Blutstein T, Benham Rs, Mccarthy Mm, Mong Ja; Pitchers Kk, Balfour Me, Lehman Mn, Richtand, Nm, Yu L, Coolen, Lm .; Bradley Kc, Meisel RI. Haughey Hm, Fleckenstein Ae, Hanson Gr .; Mitchell Jb, Gratton A .; Melis Mr, Argiolas A .; Stahl Sm.; Traish Am, Botchevar E, Kim Nn .; Larson Et; Norris Do; Gordon Grade E; Sumtraish Am, Botchevar E, Kim Nn .; Mers Ch; Kleitz-Nelson Hk; Dominguez Jm; Bali Gf; Krüger Th; Schiffer B; Eikermann M; Haake P; Gizewski E; Schedlowski M; Kratochvíl S .; Moll Jl, Brown Cs .; Graham Md; Pfaus Jg; Hull Em; Lorrain Ds; Du J; Matuszewich L; Lumley La; Putnam Sk; Moses J.

[098] - PERGOLIDA - Pergolida belongs to a group of medicines called Antiparkinsónicos and is used in association

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37/80 association with levodopa in the treatment of signs and symptoms of Parkinson's disease, with 0.25mg tablets. It has its pharmacological action as a dopamine agonist (State of the Art).

[099] - Our objective of the use of this substance in the sexual sphere coincides with DOPAMINERGIC ACTION, AS TO THE INCREASE OF SEXUAL DESIRE AND THE ELICIATION OF SEXUAL STIMULUS, consequently FAVORING THE MECHANISM OF DESIRE, STIMULATION AND ORGASTIC, AS MUCH IN MEN AS MALE IN MEN .

[100] - Some works prove the facilitative action of Monoamines in sexual behavior, such as: Holder Mk, Hadjimarkou Mm, Zup SI, Blutstein T, Benham Rs, Mccarthy Mm, Mong Já; Frohmader Ks, Wiskerke J, Wise Ra, Lehman Mn, Coolen Lm; Holder Mk, Hadjimarkou Mm, Zup SI, Blutstein T, Benham Rs, Mccarthy Mm, Mong J.

[101] - APOMORPHINE - Apomorphine is a synthetic derivative obtained by treating morphine with concentrated hydrochloric acid. It has structural similarities with dopamine. According to Heaton et al. (2000), it can be classified as a STARTING AGENT AND ELICIATOR of the CENTRAL ACTION ERECTION. Data from its pre-clinical evaluation, as well as its mechanism of action, have been discussed previously and will not be mentioned here. In clinical studies, subcutaneous administration (S.C.) of apomorphine (0.25 -1.0 g) was effective in inducing erections. However, several reports of severe nausea have occurred demonstrating an unacceptable adverse effect / benefit relationship. This fact led to the development

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38/80 of a sublingual (SL) form of administration for apomorphine that resulted in its fast and efficient absorption, with a plasma half-life (t1 / 2) of 2 to 3 h, in addition to presenting the advantage, in face of oral forms of administration, to be unchanged by food intake. Pharmacokinetic data on apomorphine are scarce. It is known that it is very little absorbed through the gastrointestinal tract and is quickly eliminated from the body, due to its high volume of distribution and rapid biotransformation. However, when administered sublingually, apomorphine does not suffer a first-pass effect, quickly reaching the plasma levels necessary for the therapeutic effect. However, nausea is also the main undesired effect when administered sublingually, with an episode reported by about 7% of patients in clinical studies. This effect occurs through the activation of subtype d2 receptors, mainly peripheral ones, which ultimately lead to decreased gastric motility. Other adverse events such as emesis, tiredness, yawning and dizziness are dose dependent - and little reported or of low intensity in therapeutic doses. With apomorphine SI, the desired central effect is already achieved in doses less than 1 mg. A clinical study carried out with 457 patients with de without a major organic component reported a success rate in sexual intercourse of 45.8, 52.0 and 59.6% for doses of 2.4 and 6 mg, respectively, compared to placebo values around 30%. Several other phase III studies have led to the conclusion that the ideal dose for treatment is 3 mg. At this dose, the erection occurs, on average, in 23 min, with

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39/80 an average duration of 13 min. Other clinical studies have demonstrated the pro-erectile effect of treatment with apomorphine sl in normal, impotent and alcoholic men, confirming its effectiveness in the treatment of. The drug can be used in patients with benign prostatic hyperplasia, coronary artery disease and hypertension.

[102] - Apomorphine has no analgesic properties due to its structural similarity to morphine and no ability to induce addiction. Together, these data point to apomorphine sl as an effective and safe alternative for the treatment of several cases of D.E. Apomorphine is a dopaminergic agonist and has an effect on sexual function, as it has central action and also peripheral action on genital vessels.

[103] - In cases of sexual dysfunction, such as desire dysfunction, SHE IMPROVES LIBIDO, due to the action of central dopaminergic agonist in men and women, as well as arousal and erectile dysfunction, both at the penile and clitoral levels, because it has vasodilating action on sinusoidal and helicinal capillaries of the penis and clitoris, improving penile and clitoral erection. Apomorphine in combination with minoxidil can determine a better vasodilator action, both at the penile and clitoral levels, as well as being industrialized with less concentration, aiming at minor deleterious effects. The starting point at the brain level is sexual arousal. Dopaminergic agonists (ad) exert their effect by stimulating localized dopaminergic receptors

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40/80 in the postsynaptic neuron. Because they have this direct action on the receptor, they do not need to be previously metabolized to act as levodopa.

[104] - It also stimulates sexual behavior and has a sexual excitatory role in the hypothalamic and peripheral limbic system.

[105] - We know that the use of this substance in adequate doses, as well as its precursors and derivatives, directly or indirectly, have activity and a positive influence on sexual behavior, can correct various sexual dysfunctions, of the phases of desire, excitation and orgasms such as low libido, hypoactive desire, altered stimulation, orgasmic dysfunction secondary to these dysfunctions, dyspareunia due to lack of lubrication and stimulation, sexual dysfunctions secondary to menopause, both male and female.

[106] - Differences in the state of the art are:

[107] - a) Different Concentrations [108] - b) Associations with Minoxidil [109] - c) Therapeutic Indications [110] - d) Beneficiation for both sexes.

[111] - Several authors have been studying the role of Apomorphine in sexual behavior, such as scientific works that collaborate with this patent application: Allers Ka; Richards N; Scott L; Weatman C; Cheung J; Reynolds D; Casey Jh; Wayman C; Allers Ka; Richards N; Scott L; Sweatman C; Cheung J; Reynolds D; Casey Jh; Wayman C; Riley A; Main M; Morgan F;

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Kings ParkCwmann, Lampeter, Carmarthenshire; RileyA; Main M; Morgan F; Lampeter, Carmarthenshire; Freo U; Merico A; Ermani M; Ori C) Hannan Jl; Blaser Mc; Oldfield L; Pang Jj; Adams Sm; Pang Sc; Adams Ma; Graham Md; Pfaus Jg; Allers Ka; Richards N; Scott L; Sweatman C; Cheung J; Reynolds D; Casey Jh; Wayman. Ç.

[112] - PROSTAGLANDINES (PGE 1) - The

Prostaglandins have several holdings in the human economy. In the sexual sphere it contributes to increased sexual arousal and the intensity of orgasm. Pg1 - prostaglandin and Alprostadil - Prostaglandin is a substance that exists in the human body and is metabolized in the lungs, liver. This substance allows the dilation of the arteries and consequently the filling of the corpora cavernosa, enabling the swelling of the penis, and the uterine vessels, promoting uterine erection, producing vasodilation in the clitoral cavernous bodies and vessels of the female genitalia, of the large and small lips, vulvar introitus, etc. PROSTAGLANDINE IS ANTAGONIZED, that is, its effect is diminished by other drugs, such as ADRENALINE AND NORADRENALINE.

This physiological mechanism may be the explanation why, both men and women, in situations of STRESSED STRENGTH, sometimes CANNOT HAVE A SEXUAL GOOD MOMENT, simply because they have a marked release of endogenous adrenaline and which limits their erection, because it blocks endogenous prostaglandin PG1, thereby preventing vasodilation of vasavasorum capillaries and penile vessels,

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42/80 forms the influx of blood to the penis, which produces penile erection.

[113] - Thus, adrenaline and / or norepinephrine blocks prostaglandin, especially PG1, which can normally occur at a time of stress, for both men and women. In men it prevents erection and in patients in chronic stress this can be the pathophysiological mechanism of erectile dysfunction, caused by stress. In women, as the erection is analogous to vaginal lubrication and libido, there is a reduction in vaginal secretion, causing vaginal dryness, producing poor quality of penetration and, therefore, poor orgastic quality or bad orgastic intensity, another aspect is that

PG1 HAS PARTICIPATION IN THE EXCITATORY MECHANISM, INCREASING SEXUAL EXCITATION, lubrication and orgasmic intensity, which is essential for a good sexual relationship.

[114] - A popular treatment technique, not so used today, after the advent of Sildenafil, which involves injecting a small amount of medication directly into the erectile tissue of the penis. (State of the Art). Erection usually occurs within 10 minutes and lasts 30 to 90 minutes.

In most vessels, PG1 prostaglandins are more potent vasodilators and this action mainly involves arterioles, precapillary sphincters and postcapillary venules. Prostaglandins are also produced in the CNS, in vessels and neurons, participating in the mechanisms of sleep and awakening. It is also possible that post-orgasmic sleep in the resolution phase, very

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43/80 longer in men than in women, may have a component of the release of brain prostaglandins. The state of the art already exists - use of prostaglandin pge1 - for the use of erectile dysfunction, as is the case with Alprostadil, Caverjet, etc., however, they are used for intra-urethral application and for injection into the body of the penis. This drug causes vasodilation, stimulates the muscles of the uterus and intestine and also inhibits platelet aggregation. It is possible that clinically, in the case of the woman's orgastic difficulty, when the woman is experiencing a high degree of excitement and anxiety and at the same time is in the pre-orgasmic moment where the release of prostaglandins has already occurred, causing vasodilation in the myometrial vessels, which determines the influx of blood into the uterus, determining the uterine erection and the uterus lifting, placing it in a position of previously movable flexion. In cases of stress, the catecholamines are released norepinephrine and adrenaline, as previously mentioned, it blocks PG1 and it is possible that due to the high degree of anxiety worsened by the concern of not being able to reach orgasm, which also occurs in male patients, with fear of performance, blocking the release of PG1 may occur, preventing non-vasodilation. This may explain pelvic congestion that the woman who is unable to have orgasms, and is even a frequent complaint to clinicians and gynecologists of the famous pain in the lower abdomen. Such a clinical complaint can be explained by this mechanism of adrenaline and norepinephrine release, blocking PG1 and preventing vasodilation, preventing penile, clitoral, erection of the female genitals, and the sexual excitatory mechanism. On the other hand, in this

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44/80 moment it is possible that, before the necessary and adequate physiological time of vasodilation to drain blood flow, producing penile and uterine erection, early vasoconstriction occurs, remaining partial myometrial blood content, determining the pelvic congestion process , with the consequent pain and malaise in the lower abdomen. It is also necessary to comment that such phenomenon occurs in a situation in which the man has an orgasm before his partner, which is frequent in the Early Ejaculators, and she is in a high degree of excitement, however, is unable to develop the action potential. of orgasm. In this case, the sexual partner, through other forms of sexual stimulation, such as oral, manual, penile, etc., continue to perform stimulation in the woman's clitoral region and in other body regions, in the sense to produce an increase in sexual and neuronal stimulation, to reach the action potential of orgasm. Prostaglandins cause greater capillary permeability, which helps and produces vaginal exudate, that is, vaginal lubrication, in addition to sexual arousal. Its action varies according to the target cell, and its useful life is very short. Its synthesis and release in the female endometrium are regulated by estrogen. The fact that synthesis and release in the endometrium is regulated by estrogen explains the fact of vaginal dryness in women in menopause, also associated with reduced libido and poor quality of sexual performance.

[115] - We know that the use of this substance in adequate doses, as well as its precursors and derivatives, directly or indirectly, have activity and a positive influence on

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45/80 sexual behavior and can correct various sexual dysfunctions, from the phases of desire, excitement and orgasms, including, such as low libido, hypoactive desire, alteration of the stimulus, due to its central stimulating action, orgasmic dysfunction secondary to these dysfunctions, dyspareunia due to lack of lubrication and stimulation, sexual dysfunction secondary to the climacteric, both male and female. What differs in the state of the art and the advantages of this patent are:

[116] - A) Different Concentrations [117] - B) Associations with Minoxidil [118] - C) Therapeutic Indications Benefited Both Sexes.

[119] - d) Different Forms of Presentation, while the state of the art, presents injectable, intraurethral forms. We present, in this claim, other forms of better use, painless, of better acceptance by the patient and with better costs, which can be used for both sexes, such as the forms: cream, gel, vaginal ova, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets, oral tablets, and another advantage is that it can benefit both men and women, who have sexual dysfunction, which gives them the character of novelty, industrial applicability.

[120] - Some authors have confirmed the participation of prostaglandins in sexual behavior, such as: Reis,

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JMSM; Rodrigues, O.M .; Monesi, A. A; Liao Q; Zhang M; Geng L; Wang X; Song X; Xia P; Lu T; Lu M; Liu V.

[121] - MELATONIN - The pineal gland (located in the center of the brain) starts the production of melatonin in the dark cycle, to help our body regulate the sleep cycle (circadian cycle). As we age, the amount of melatonin produced by our body decreases. Scientists believe that this is the main cause of elderly people sleeping poorly. Currently we know that melatonin is a hormone that has different functions acting as an endocrine or paracrine agent (Stefulj Et All, 2001). In most organs and tissues, the arrival of melatonin occurs via the circulatory pathway and therefore reflects the activity of the pineal gland. In the retina, melatonin is produced rhythmically locally and also has the function of adapting animals to the dark. It also has a stimulating action on sexual behavior, has a sexual excitatory role in the hypothalamic and peripheral limbic system. It produces action in the phases of desire, excitement and orgasms, in men and women. We know that the use of this substance in adequate doses, as well as its precursors and derivatives, directly or indirectly, have a positive activity and influence on sexual behavior and can correct various sexual dysfunctions in the phases of desire, excitement and orgasm, both male and female . There is no state of the art in these claimed conditions, and can be produced according to the clinical and scientific interest of the market, in the forms: cream, gel, vaginal ova, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid , aerosol, sublingual tablets,

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47/80 scheduled release tablets, oral tablets, and another advantage is that it can benefit both men and women, with sexual dysfunction, such formulations may be industrialized, in the forms presented, which gives them the character of novelty, applicability industrial and inventive step. Several authors collaborate with the action of melatonin as a stimulant in human sexual behavior, such as some scientific works: Pozo Mj; Gomez-Pinilla Pj; Camello-Almaraz C; MartinCano Fe; Pascua P; Rol Ma; Acuna-Castroviejo D; Camello Pj; Binfaré Rw; Mantle-Vani M; Budni J; Santos Ar; Rodrigues Al; Wu Yh.Zhou Jn.Balesar R, Unme-Hopa U, Bao A. Jockers R, Van Heerikhuize J, Swaab Df.

[122] -SILDENAFIL- SILDENAFIL is an oral drug that was approved by the FDA (Food And Drug Adminstration Usa) in 1998, and that was a major breakthrough in the treatment of erectile dysfunction. There is the state of the art, where it is presented in dosages ranging from 25, 50 and 100 mg. Oral use. It is a selective vasodilator of the arteries of the corpora cavernosa, acting as a selective inhibitor in the pd5, thus favoring an erection of the corpora cavernosa. In patients with more severe or older pathologies, its use will not be as indicated. It is contraindicated for people with heart problems or who use nitrate. The most common side effects are tachycardia, headache, hypotension, gastritis, diarrhea, visual disturbances, and in cardiac or hypertensive patients who have nitrates, the risk of heart problems is high. This medication is contraindicated for patients

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48/80 that use concomitantly with nitrates and in the rare visual disease retinitis pigmentosa. The state of the art exists for use of Sildenafil, orally, in dosages of 25, 50 and 100 mg.

[123] - However, this PATENT CLAIMS THE USE OF SILDENAFIL IN THE CONCENTRATIONS OF (0.1 MG TO 500 MG) ASSOCIATED WITH MINOXIDIL, for several presentations, and not the isolated use of Sildenafil by mouth, as already stated in the state of the technique.

[124] - The association with minoxidil has an action on sexual behavior, playing a role in potentiating the vasodilating action, improving sexual performance, both in men and women. We know that the use of this substance in adequate doses, as well as its precursors and derivatives, directly or indirectly, have a positive activity and influence on sexual behavior and can correct various sexual dysfunctions in the phases of desire, excitement and orgasm, both male and female . There is no state of the art, of this substance associated with minoxidil and with this clinical indication, for both sexes.

[125] - Under these conditions, they can be produced according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal eggs, vaginal creams, ointment, nasal spray, sublingual spray, vaginal spray, liquid, aerosol , sublingual pills, scheduled release pills, oral pills and another advantage is being able to benefit both men and women, who have sexual dysfunction.

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49/80 [126] - The presentations recommended in this patent may be industrialized, according to the appropriate doses, the clinical-scientific interest, in the forms presented, which gives them the character of novelty, industrial applicability and inventive step.

[127] - VARDENAFIL - VARDENAFIL HYDROCHLORIDE - there is the state of the art of this medication, orally, only Vardenafil 20 mg - isolated, which is indicated for the treatment of erectile dysfunction. Its absorption is done quickly, approximately 15 minutes and continues to act for at least four or five hours. With two presentations available (10 or 20 mg).

[128] - The claim of this patent refers to VARDENAFIL IN THE CONCENTRATION OF 0.1 MG TO 200 MG (not belonging to the state of the art) IN ASSOCIATION WITH MINOXIDIL and in several other forms of presentations, as mentioned above, which gives it novelty, inventive activity and industrial applicability. It acts on sexual behavior, plays a role as a vasodilator improving sexual performance, both in men and women. We know that the use of this substance in adequate doses, as well as its precursors and derivatives, directly or indirectly, have a positive activity and influence on sexual behavior and can correct various sexual dysfunctions in the phases of desire, excitement and orgasm, both male and female . There is no state of the art, of this substance associated with minoxidil and with this clinical indication, for both sexes. In this conditions,

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50/80 and can be produced according to the clinical-scientific and market interest, in the forms: cream, gel, vagina ova, vaginal creams, ointment, nasal spray, vaginal spray, liquid, aerosol, sublingual tablets, release tablets programmed, oral pills, and another advantage is being able to benefit both men and women, who have sexual dysfunction. The presentations recommended in this patent may be industrialized, according to the appropriate doses, clinical and scientific interest, in the forms presented, which gives them the character of novelty, industrial applicability and inventive step.

[129] - TALADAFIL - The effect of this medication is quite prolonged, reaching 48 hours. It also has some of the side effects such as headache, rhinitis. It was licensed in doses of 10 and 20 mg. The medication should be taken some time before the scheduled time for sexual activity. Nitrate patients cannot use it. As shown above, the state of the art exists for Tadalafil alone, orally, while the claim for this patent consists of the association of Tadalafil in the concentration of (0.1 mg to 200mg), in different concentrations and different presentations (not state of the art ). It acts on sexual behavior, plays a role as a vasodilator improving sexual performance, both in men and women. We know that the use of this substance in adequate doses, as well as its precursors and derivatives, directly or indirectly, have a positive activity and influence on sexual behavior and can correct various sexual dysfunctions in the phases of desire, excitement and orgasm, both male and female . There is no state of

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51/80 technique, of this substance associated with minoxidil and with this clinical indication, for both sexes. Under these conditions, they can be produced according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal ova, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, aerosol, sublingual tablets, scheduled release, oral pills, and another advantage is being able to benefit both men and women, who have sexual dysfunction. The presentations recommended in this patent may be industrialized, according to the appropriate doses, clinical and scientific interest, in the forms presented, which gives them the character of novelty, industrial applicability and inventive step.

[130] - FENTOLAMINE - FENTOLAMINE may have a similar action to Sildenafil, as it would increase blood flow (this showed positive results in Mexican women who were part of a study group. Some drugs are already part of the state of the art, as is the case of - FENTOLAMINE MESILATE - is used orally, in isolation, but not associated with minoxidil.The base of these drugs is FENTOLAMINE FENTOLAMINE has been used intracavernously, combined with papaverine and / or prostaglandin since 1985 (Sharlip 1998) (state of the art), BUT THERE IS NO PHENTOLAMIN ASSOCIATED WITH MINOXIDIL It acts on sexual behavior, plays a role as a vasodilator improving sexual performance, both in men and women. We know that the use of this substance in doses as well as its precursors and derivatives, directly or indirectly

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52/80 direct, have activity and positive influence on sexual behavior and can correct various sexual dysfunctions of the phases of desire, excitement and orgasm, both male and female. There is no state of the art, of this substance associated with minoxidil and with this clinical indication, for both sexes, under these conditions, which can be produced according to the clinical scientific and market interest, in the forms: cream, gel, vaginal ova , vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets, oral tablets, and another advantage is that it can benefit both men and women, who have sexual dysfunction. The presentations recommended in this patent may be industrialized, according to the appropriate doses, clinical and scientific interest, in the forms presented, which gives them the character of novelty, industrial applicability and inventive step.

[131] - GABA-ACID AMINOBUTYRIC RANGE - There is the state of the art in concentrations of (750 mg), however, there is no state of the art, in the concentrations of (25 mg to 600 mg) and (850 mg to 1500 mg) associated with minoxidil, and in various forms of presentations other than oral only. GABA is the main inhibitory neurotransmitter in the central nervous system of mammals. It plays an important role in regulating neuronal excitability throughout the nervous system. In humans, gaba is also directly responsible for regulating muscle tone. Behaviorally, the inhibitory action of the neurotransmitter GABA, through the activation of the receptor

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GABA-A, is related to aggressive behavior and impulsivity in humans. In vertebrates, gaba acts on inhibitory synapses in the brain by binding to specific transmembrane receptors and on the plasma membrane of both pre- and postsynaptic neurons. Currently we have the best known three classes of GABA receptors: GABAA and GABAC, which are ionotropic receptors and GABAB, metabotropic receptors, a receptor linked to a G protein, which open ion channels through intermediaries. It is an important neurotransmitter, acting as a neurosynaptic inhibitor, because it binds to specific receptors. As a peculiar neurotransmitter, gamma aminobutyric acid induces the inhibition of the central nervous system and can cause sedation. This is because neuronal cells have specific receptors for gaba when it binds to receptors, a channel opens where chloride ion enters the neuronal cell, causing the cell to become hyperpolarized, making depolarization difficult and, as a consequence, giving decreased neuronal conduction, causing CNS inhibition. The neurons that secrete GABA are called gabaergics and have an inhibitory action mainly on receptors in the synapses of adult vertebrates. Gaba activity will either be excitatory or inhibitory depending on the direction (into or out of the cell) and magnitude of the ionic currents controlled by the GABAA receptor. The body synthesizes gaba from glutamate using the enzyme l-glutamic acid decarboxylase and pyridoxal phosphate (which is the active form of b6) as a cofactor. This process converts the main excitatory neurotransmitter (glutamate) into one of the main inhibitors (gaba). Drugs that act as gaba receptor agonists

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54/80 (known as gabaergic drugs or gaba analogs) and may increase the available gaba amount; usually have relaxing, anti-anxiety and anticonvulsant effects. However, when administered orally, gaba has effects outside the central nervous system (for example, decreased muscle tone.

[132] - WOMEN'S ORGASTIC DIFFICULTY - Despite the great pre-orgasmic excitement, probably due to the high concentration of glutamate in the hypothalamic limbic system, and, as glutamate produces GABA, with GABA inhibitory action and GABA inhibits glutamate, thus , making homeostasis present, with regulation at the receptor level. In the sexual sphere it is very possible that a group of women with a woman's orgasmic difficulty, which may be due to a high concentration of glutamate and when the gaba inhibits it performs a “micro sexual sedation” leaving in an ideal concentration, leaving a neuronal hyperpolarized condition , unblocking in some way, the neuronal pathways necessary for the orgasm action potential to occur. The anti-anxiety, relaxing action of the gaba, can be extremely beneficial, in the moment of sexual hyperexcitation, of the woman with orgastic difficulty, and that in some way, can prevent the hyperpolarized action potential, determining the normal depolarization in the cell membrane potential and thereby releasing the action potential with an ideal voltage to trigger orgasm. In patients with hypersexuality in the group of patients with bipolar disorder it is possible that they can benefit from the administration of gaba, in adequate doses, obtaining control of sexual impulsivity. The mechanism is not yet established, however, it is

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55/80 It is very possible that such patients have irregular electrical activity, with high frequencies of neuronal firing in areas containing sexual brain cells and the use of gaba should regulate these neuronal firings, as if they were epileptogenic foci in the hypothalamic limbic system. By regularizing the frequency, you can clinically obtain the patient's psycho-social-sexual-behavioral balance, with hypersexuality and abusive and harmful sexual behavior. Like some drugs that act as gaba receptor agonists (known as gabaergic drugs or gaba analogs) or increase the available amount of gaba, they usually have relaxing, anti-anxiety and anticonvulsant effects. Therefore, these associations with minoxidil, can be beneficial for treating both male and female sexual dysfunctions. As gaba has a central inhibitory action, minoxidil with a local action, may have a combination of effects, producing an adequate sexual response for the phases of arousal, orgasm and even the resolution phase. It acts on sexual behavior at the central level, modulating central neurochemical reactions, improving sexual performance, both in men and women. The gaba has an important participation in the orgasmic mechanism, because in orgasm, it found in high concentrations, basically, in the moment after orgasm. He is also one of those responsible for the state of satisfactory resolution, in the post-orgasmic moment. We know that the use of this substance in adequate doses, as well as its precursors and derivatives, directly or indirectly, have activity and can beneficially regulate the positive influence on the

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56/80 sexual behavior and can correct or modulate neuronal synapses, improving clinically, various sexual dysfunctions of the phases of desire, excitement and orgasms, both male and female. There is no state of the art, of this substance associated with minoxidil and with this clinical indication, for both sexes, under these conditions. They can be produced according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, release tablets programmed, oral pills, and another advantage is being able to benefit both men and women, who have sexual dysfunction. The presentations recommended in this patent may be industrialized or not, according to the appropriate doses, clinical-scientific and commercial interest, in the forms presented above, which gives them the character of novelty, industrial applicability and inventive step and commercial condition.

[133] - Some studies demonstrate the action of GABA by modulating actions in the SNC, which can contribute to adjust sexual function, such as: J Psychopharmacol, 2010; Leriche M, Méndez M, Zimmer L, Bérod A.

[134] - BROMOCRIPTINA-A BROMOCRIPTINA is a dopaminergic agonist of the ergolinic agonist type. They are drugs derived from ergot alkaloids, having a direct action on dopaminergic receptors. The first ad used in PD was Bromocriptine in 1974. Bromocriptine has an agonistic action on d1 receptors. The fact that Bromocriptine is an agonist

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57/80 dopaminergic, in situations where we have increased prolactin, in an important or subclinical way, and the symptom of reduced libido is present, both in men and women and also in men with erectile dysfunction due to hyperprolactinemia, it will be very well indicated. It is indicated for hyperprolactinemia and prolactin-producing tumors.

[135] - Reducing the concentration of prolactin, it increases the action of dopamine. The claim of this patent serves Bromocriptine in the concentration of 0.01 mg to 100 mg for use alone or associated with minoxidil. It acts on sexual behavior, improving sexual performance, both in men and women. We know that the use of this substance in appropriate concentrations and clinical indications, have a positive activity and influence on sexual behavior and can correct various sexual dysfunctions in the phases of desire, excitement and orgasms, both male and female. In the case of patients with HYPOACTIVE DESIRE, due to its dopaminergic agonist effect, dopamine would increase, reducing prolactin and increasing the effect of sexual stimulant. There is no state of the art of this substance associated with minoxidil and with this clinical indication, for both sexes. In patients with orgasmic difficulty and hyperactive desire, it would have a good therapeutic indication. Therefore, under these conditions, it can be produced according to the clinical-scientific and market interest, in the forms: cream, gel, vagina eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, ae

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58/80 rosol, sublingual pills, programmed release pills, oral pills, and another advantage is being able to benefit both men and women, who have sexual dysfunction, such as hypoactive desire, lack of sexual interest, orgasmic dysfunction and difficulty erective ..

[136] - The presentations recommended in this patent may be industrialized, according to the appropriate doses, scientific clinical interest, in the forms presented, which gives them the character of novelty, industrial applicability and inventive step. Several authors have reported the inhibition of prolactin as an improvement in sexual behavior, such as this work: Drago F; Meyerson Bj; Krüger Th; Schiffer B; Eikermann M; Haake P; Gizewski E; Schedlowski M., among others [137] - IOIMBINA-A lOIMBINAis an alpha adrenergic blocker extracted from an African tree and used as a natural remedy to improve libido. They are being evaluated for the treatment of sexual arousal disorder in postmenopausal women with promising results at first. Understanding the mechanisms of neurotransmitters, peptides and other chemical components, which participate in all sexual phases and responsible for each phase of sexual function, allows physicians to predict how certain drugs may affect the sexual response and provides the basis for the development of new treatments pharmacological measures for male and female sexual dysfunctions. Yohimbine blocks presynaptic alpha-2 adrenergic receptors, somewhat preventing venous vasoconstriction.

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Its peripheral vasodilating action is similar to that of reserpine, although weaker and of shorter duration. The effect of yohimbine on the peripheral autonomic nervous system is an increase in parasympathetic (cholinergic) activity and a decrease in sympathetic (adrenergic) activity. In male sexual performance, erection is linked to cholinergic activity and alpha-2 adrenergic block, which can theoretically result in increased penile tone, decreasing the emptying of the flow in the penis or both, causing erectile stimulation, without increasing sexual desire. . Yohimbine produces vasodilation of the cavernous body due to the alpha antagonistic effect. Yohimbine alone, but not in association with minoxidil, is state of the art, for indications such as mydriatic and sympatholytic medication and even for sexual activity. Yohimbine alone (state of the art) for use in tablets, orally, has been used for male sexual dysfunctions, of psychogenic, vascular or diabetic origin, however, however, there is no state of the yohimbine technique associated with minoxidil 0.01% at 30%, with indication for the treatment of female and male sexual dysfunctions, including in diabetic patients. Yohimbine easily penetrates the CNS and produces a complex pattern of responses at doses lower than those required to produce alpha-adrenergic block. These include excitement. Therefore, patients with erectile dysfunction and some excitatory difficulty, as well as women with orgastic dysfunction can benefit from the use of this combination of minoxidil and yohimbine.

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60/80 [138] - The advantage and novelty, as well as industrial applicability in relation to the claim of these new pharmaceutical compositions, contained in this PI, is in the association of minoxidil with the other various drugs, as well as, in relation to the various ways of presenting and applying the association's product. It differs from the state of the prior art, in addition to the associations, the concentrations, indications and presentations of the product, the fact that its use consists in drug treatment of various female and male sexual dysfunctions, referring to the human sexual response, regarding the phases of desire, excitement and orgasms, such as: female anorgasmia, female orgasmic difficulty, female dyspareunia, reductions in female sexual desire, reduced vaginal lubrication, changes in the sexual stimulation phase, as well as in the treatment of male sexual dysfunctions, such as improves erection in normal men who are interested in increasing erection, delayed ejaculation, male dyspareunia, changes in libido, changes in the stimulus phase, as well as various concentrations and presentations of these associations, which will be better adapted to each clinical case. It acts on sexual behavior, improving sexual performance, both in men and women. We know that the use of these substances in appropriate concentrations and clinical indications, have positive activity and influence in solving difficulties in human sexual behavior and can correct various sexual dysfunctions both male and female. There is no state of the art, of this substance associated with minoxidil and with this clinical indication.

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61/80 single, for both sexes. Under these conditions, they can be produced according to the scientific and market clinical interest, in the forms: cream, gel, vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, tablets scheduled release, oral pills, and another advantage is being able to benefit both men and women, who have sexual dysfunction. The presentations recommended in this patent may be industrialized, according to the appropriate doses, clinical and scientific interest, in the forms presented, which gives them the character of novelty, industrial applicability and inventive step.

[139] - ENDORPHINE - This group of substances, called endorphins, are neurotransmitters, just as noradrenaline, acetylcholine and dopamine are chemical substances used by neurons in the communication of the nervous system. It is a hormone, a chemical substance that, carried by the blood, communicates with other cells. Its name comes from the words endo (internal) and morphine (analgesic). Endorphins were discovered in 1975. Twenty different types of endorphins were found in the nervous system, beta-endorphin being the most efficient because it is the one that gives the most euphoric effect to the brain. It consists of 31 amino acids. The beta endorphin claimed in this patent has a highly beneficial action on sexual dysfunctions. Endorphins are produced in response to physical activity; in sex, endorphins are responsible for relaxation, analgesia, euphoria and have a high participation in orgasmic moments, where they are found in increased concentrations.

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It is also responsible for the feeling of fullness and well-being in the post-orgasmic moment. It has its indication in this patent for patients with dysfunction in sexual stimulation, dyspareunias of idiopathic and or psychogenic origin, due to its analgesic effect; woman's orgasmic difficulty, improvement of the sensation of orgasmic fullness and relaxation in the post-orgasmic moment

[140] - STROGENS - The name, generally attributed to the 17-beta isomer of estradiol, a c18 steroid flavored with hydroxyl group in the 3-beta and 17-beta position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. In humans, it is produced mainly by the ovaries and placenta. It is also produced by fatty tissue in men and in postmenopausal women. The 17-alpha isomer of estradiol binds weakly to estrogen receptors and exhibits little estrogenic activity in tissues responsive to this hormone. Several isomers can be synthesized. The most sexually interesting estrogen is 17-b-estradiol. There are several forms of presentation and dosages (prior art) in relation to estrogens, however, there is no state of the art of estrogens associated with minoxidil or testosterone. Another aspect that is claimed in this patent are the various forms of presentation of the associations. Libido, docility, and tenderness, notably in females, are partly dependent on estrogens. Estrogens bind to D1 dopaminergic receptors, adrenergic receptors, opioid receptors or GABA (Gamma-amino butyric acid) receptors. The participation in the improvement of sexual desire mainly in women

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63/80 with hypoestrogenism, in the peri-menopause phase, can be attributed to the stimulating action on adrenergic receptors, opioids and also on GABA receptors. Estrogens with their ability to improve NO synthesis, through the stimulation of NO synthase, and the production of prostacyclin has an important role in vasodilation and thus has its role in the process of penile erection. However, due to its vasodilating action by stimulating PG1, it has a highly important action on uterine erection, enlargement of the clitoris, enlargement of the labia majora, enlargement of the breasts, at the time of sexual arousal, of the phases of human sexual response. It is worth mentioning here that sexual desire is not exclusively due to estrogen alone or androgen. Studies show that the combined treatment of testosterone and estradiol causes a significant increase in libido. Estrogen also regulates the action of DHT (the most important regulator of ejaculation and its duration), by increasing the duration of its effect (inhibits the accelerated entry of DHT into neuronal cell structures) and thus promotes ejaculation without problems. In short, estrogen is necessary for male as well as female sexual activity. We know that the use of this substance, in adequate doses, has positive activity and influence on sexual behavior, correcting various sexual dysfunctions of the phases of desire, excitement and orgasms, such as low libido, hypoactive desire, alteration of the stimulus, orgasmic dysfunction secondary these dysfunctions, dyspareunia due to lack of lubrication and stimulation, sexual dysfunctions secondary to the female climacteric. No

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64/80 there is the state of the art, of this substance associated with minoxidil and with this clinical indication, for both sexes. Under these conditions, they can be produced according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal ova, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets, oral tablets, and another advantage is that it can benefit both men and women, who have sexual dysfunction, in cases of delayed ejaculation, premature ejaculation, for the regulation of the time and duration of ejaculatory function, in associations with testosterone, basically, in male climacteric patients. The presentations recommended in this patent may be industrialized, according to the appropriate doses, scientific clinical interest, in the forms presented, which gives them the character of novelty, industrial applicability and inventive step. Several works collaborate with the importance of estrogens in human sexual activity, such as: Gleicher N; Weghofer A; Barad D H .; Nappi Re; Albani F; San-Tamaria V; Tonani S; Magri F; Martini E; Chiovato L; Polatti F; Traish Am; Botchevar E; Kim Nn; Le Page Y; Diotel N; Vaillant C; Pellegrini E; Anglade I; Mérot Y; Kah O; Azcoitia I; Santosgalindo M; Arevalo Ma; Garcia-Segura Lm; Krüger Th; Schiffer B; Eikermann M; Haake P; Gizewski E; Schedlowski M; Orts A, Vila J. Esplugues J, Brugger; Traish Am, Botchevar E, Kim Nn.

[141] - This patent refers to a group of interrelated inventions, which constitute a single concept

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65/80 inventive, with the advantage of benefiting a larger group of patients with various types of sexual dysfunction, which affect both male and female patients.

[142] - These associations aim to produce drugs for drug treatments with new drugs for female and male sexual dysfunctions, notably related to the phases of desire, excitement and orgasm, as well as for treatment for the so-called dysfunctions, dyspareunias and vaginismus .

[143] - BELOW WILL BE DEMONSTRATED

THE CLAIMS.

[144] - (001) - MINOXIDIL AND DRUG ASSOCIATIONS for the treatment of female and male sexual dysfunctions, MINOXIDIL IN THE CONCENTRATIONS OF (0.01% TO 30%) CHARACTERIZED BY BEING ASSOCIATED WITH (DHEA) - DEHIDROEPIANDROSTERONE (0.1 MG A 150 MG) indicated for woman's orgasmic difficulty, anorgasmia, improved sexual desire, excitatory difficulty, improved vaginal lubrication, dyspareunia due to low sexual arousal, improved vaginal lubrication, improved sexual disposition in women, for the male population the indication is for cases of erectile dysfunction, improvement of sexual performance in men, said to be normal; men with hypoactive desire, diabetic patients and with vascular changes and reduced libido, hypoactive desire in both sexes. They can be produced or not, according to the interest

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66/80 clinical-scientific and market, in the forms: cream, gel, vaginal ova, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets, oral tablets .

[145] (002) -MINOXIDIL AND DRUG ASSOCIATIONS for the treatment of female and male sexual dysfunctions, MINOXIDIL IN THE CONCENTRATIONS OF (0.01% TO 30%) CHARACTERIZED BY BEING ASSOCIATED WITH (DHEA) DEHIDROEPIANDROSTERONE (0.1 MG A150 MG) AND AO 17-B- ESTRADIOL (0.1 MG A15 MG) indicated for the treatment of women's orgastic difficulties, anorgasmia, improvement of sexual desire, improvement of vaginal lubrication, increased sexual stimulation, vaginal dryness, vaginismus, dyspareunia due low vaginal lubrication and sexual difficulties and reduced sexual activity in the pre, menopause and post-menopause phases, improved sexual disposition in both sexes, delayed ejaculation and premature ejaculation. They can be produced or not, according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets, oral tablets.

[146] - (003) - MINOXIDIL E

DRUG ASSOCIATIONS for the treatment of female and male sexual dysfunctions, MINOXIDIL IN THE CONCENTRATIONS OF (0.01%

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67/80

30%) CHARACTERIZED FOR BEING ASSOCIATED WITH TESTOSTERONE (0.1 MG TO 1000 MG), indicated for the activation of sexual desire in men and women, erectile dysfunction with low libido, erectile dysfunction, delayed ejaculation, orgasm difficulty for women, anorgasmia, Sexual hypodisease in both sexes, Sexual hypoactivity in both sexes, improved vaginal lubrication, dyspareunia due to low vaginal lubrication and reduced sexual desire. They can be produced or not, according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets, oral tablets.

[147] - (004) - MINOXIDIL AND DRUG ASSOCIATIONS for the treatment of female and male sexual dysfunctions, MINOXIDIL IN THE CONCENTRATIONS OF (0.01% TO 30%) CHARACTERIZED FOR BEING ASSOCIATED WITH TESTOSTERONE (0.1 MG TO 1000 MG ) and 17-B-ESTRADIOL (0.01 mg to 10 mg), indicated for the treatment of women with orgasmic difficulty in women and anorgasmia without hyperprolactinemia and / or prolactinoma, hypoactive desire in women in the menacme and menopause stages, improvement of vaginal lubrication, improvement of orgastic capacity, idiopathic vaginismus, dyspareunia due to low vaginal lubrication, dyspareunia due to hypoestrogenism and reduced libido, delayed ejaculation in men and some cases of premature ejaculation. They can be produced or not, according to the clinical and scientific interest of the market, in the forms: cream,

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68/80 gel, vaginal ova, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets, oral tablets.

[148] - (005) - MINOXIDIL E

DRUG ASSOCIATIONS for the treatment of female and male sexual dysfunctions, MINOXIDIL IN THE CONCENTRATIONS OF (0.01% TO 30%) CHARACTERIZED FOR BEING ASSOCIATED WITH PHENYLALANINE (0.1 MG / DL TO 5.0 MG / DL) and / or L-PHENYLALANINE 10%., in the form of cream, ointment, nasal spray, sublingual, aerosol, sublingual tablets, long-acting and programmed tablets, indicated for the treatment of men and women with low libido, patients with chronic pain corporeal and sexual difficulties, women with idiopathic or psychogenic dyspareunias, vaginismus, anorgasmia, orgasmic difficulty for women, improvement of sexual disposition; patients with depression and sexual disinterest, hypoactive desire, improved libido in both sexes, delayed ejaculation, erectile dysfunction in patients with depression. They can be produced or not, according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets, oral tablets.

[149] - (006) - MINOXIDIL AND DRUG ASSOCIATIONS for the treatment of female sexual dysfunctions and

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69/80 male, with MINOXIDIL IN THE CONCENTRATIONS OF (0.01% TO 30%) CHARACTERIZED FOR BEING ASSOCIATED WITH MELATONIN (0.1 MG TO 60 MG), indicated for the treatment of men and women with low libido, improvement of sexual performance, orgasmic fullness, improved sleep quality and sexual disposition. They can be produced or not, according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets, oral tablets.

[150] - (007) - MINOXIDIL AND DRUG ASSOCIATIONS for the treatment of female and male sexual dysfunctions MINOXIDIL IN THE CONCENTRATIONS OF (0.01% TO 30%) CHARACTERIZED FOR BEING A BROMOCRIPTIN ASSOCIATE (0.01 MG A100 MG) indicated in cases of hypoactive desire with hyperprolactinemia, in both sexes, erectile dysfunction in men with hypoactive desire due to hyperprolactinemia and or non-surgical prolactinoma, erectile dysfunction due to hyperprolactinemia, anorgasmia and orgasmic difficulty in women due to hyperprolactinemia. They can be produced or not, according to clinical-scientific and market interest, in the forms: cream, gel, vaginal ova, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release, oral tablets.

[151] - (008) - MINOXIDIL AND DRUG ASSOCIATIONS for Treatment of female sexual dysfunctions and

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70/80 male being MINOXIDIL IN THE CONCENTRATIONS OF (0.01% TO 30%) CHARACTERIZED FOR BEING ASSOCIATED WITH APOMORPHINE (0.1 MG TO 20 MG), indicated for treatments of men with erectile dysfunction, erectile dysfunction with hypoactive desire, delayed ejaculation, anaejaculation, hypoactive desire in women, orgasmic difficulty in women, female anorgasmia, improved vaginal lubrication, difficulty in sexual arousal, improved libido. They can be produced or not, according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets, oral tablets.

[152] - (009) - MINOXIDIL AND DRUG ASSOCIATIONS for the treatment of female and male sexual dysfunctions MINOXIDIL IN THE CONCENTRATIONS OF (0.01% TO 30%) CHARACTERIZED FOR BEING ASSOCIATED WITH PROSTAGLANDINS - PG1 (1 MCG TO 500 MCG) indicated for erectile dysfunction, improvement of sexual arousal in both sexes, female anorgasmia, orgasmic difficulty for women and reduced vaginal lubrication, pain in the lower abdomen due to orgasmic difficulty for women, hypoactive desire, reduced vaginal lubrication, patients in menopause, who cannot use estrogens, for vaginal lubrication. They can be produced or not, according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, tablets

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71/80 sublingual, scheduled release tablets, oral tablets.

[153] - (010) - MINOXIDIL ASSOCIATIONS for the treatment of female and male sexual dysfunctions MINOXIDIL IN THE CONCENTRATIONS OF (0.01% TO 30%) CHARACTERIZED FOR BEING ASSOCIATED WITH PERGOLIDA (0.01 MG A10 MG) indicated in erectile dysfunction, erectile dysfunction with hypoactive desire, erectile dysfunction in patients with Parkinson's disease, indicated in patients with Parkinson's disease with hypoactive desire, women with hypoactive desire, orgasmic difficulty, improved libido and sexual performance in both genders. They can be produced or not, according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets, oral tablets.

[154] - (011) - MINOXIDIL AND DRUG ASSOCIATIONS for the treatment of female and male sexual dysfunctions MINOXIDIL IN THE CONCENTRATIONS OF (0.01% TO 30%) CHARACTERIZED FOR BEING ASSOCIATED WITH SILDENAFIL CHLORIDATE (0.1 MG - 500MG) indicated for erectile dysfunction, improved vaginal lubrication, delayed ejaculation, woman's orgasmic difficulty, improvement of orgasmic dysfunction. They can be produced or not, according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal eggs, vaginal creams, ointment, spray

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72/80 nasal, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets, oral tablets.

[155] - (012) - MINOXIDIL AND MEDICINE ASSOCIATIONS for the treatment of female and male sexual dysfunctions, MINOXIDIL IN THE CONCENTRATIONS OF (0.01% TO 30%) CHARACTERIZED FOR BEING ASSOCIATED WITH TADALAFIL CHLORIDATE (0, 1 MG A 200MG) indicated for erectile dysfunction, reduced vaginal lubrication, delayed ejaculation, woman's orgasmic difficulty. They can be produced or not, according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets, oral tablets.

[156] - (013-MINOXIDIL AND DRUG ASSOCIATIONS for the treatment of female and male sexual dysfunctions, MINOXIDIL IN THE CONCENTRATIONS OF (0.01% TO 30%) CHARACTERIZED FOR BEING ASSOCIATED WITH VARDENAFIL CHLORIDATE (0.1 MG TO 200MGG ) indicated for the woman's orgasmic difficulty, improvement of the woman's orgasmic dysfunction, erectile dysfunction, reduced vaginal lubrication, delayed ejaculation, which can be produced or not, according to the scientific and market interest, in the forms: cream, gel , vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets, oral tablets.

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TS / ZO [157] - (014) - MINOXIDIL AND MEDICAL ASSOCIATIONS for the treatment of female and male sexual dysfunctions MINOXIDIL IN THE CONCENTRATIONS OF (0.01% to 30%) CHARACTERIZED FOR BEING ASSOCIATED WITH IOIMBINA (1 MG - 50 MG), indicated for erectile dysfunction with hypoactive desire, reduced vaginal lubrication, delayed ejaculation, orgasmic difficulty for women with hypoactive desire. They can be produced or not, according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets, oral tablets.

[158] - [015) - MINOXIDIL AND DRUG ASSOCIATIONS for the treatment of female and male sexual dysfunctions MINOXIDIL IN THE CONCENTRATIONS OF (0.01% TO 30%) CHARACTERIZED FOR BEING ASSOCIATED WITH GABA (0.1 MG TO 600MG) , indicated for premature ejaculation associated with erectile dysfunction, erectile dysfunction due to exaggerated anxiety, psychogenic erectile dysfunction, vaginismus, woman's orgasmic difficulty, delay in reaching orgasm, erectile dysfunction due to fear of performance, reduced vaginal lubrication, altered performance sex in bipolar patients and vaginismus, for genital use. They can be produced or not, according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal eggs, creams

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ΊΑ / 30 vaginal, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets, oral tablets.

[159] - (016) - MINOXIDIL AND DRUG ASSOCIATIONS to treat female and male sexual dysfunctions MINOXIDIL IN THE CONCENTRATIONS OF (0.01% TO 30%) CHARACTERIZED FOR BEING ASSOCIATED WITH GABA (850 MG TO 1500 MG) indicated for premature ejaculation associated with erectile dysfunction, erectile dysfunction due to fear of sexual performance, vaginismus, woman's orgasmic difficulty, patients with bipolar disorder, depression and hypersexuality with inappropriate socio-sexual behavior. They can be produced or not, according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets, oral tablets.

[160] - (017) - MINOXIIDIL AND DRUG ASSOCIATIONS for the treatment of female and male sexual dysfunctions MINOXIDIL IN THE CONCENTRATIONS OF (0.01% TO 30%) CHARACTERIZED FOR BEING ASSOCIATED WITH BETA-ENDORFINE (0.1% A 30%) indicated for idiopathic dyspareunias, psychogenic dyspareunias, improvement of the quality of orgasm, improvement of the quality of the post-orgastic state, reduction of sexual anxiety in both sexes. They can be produced or not, according to the clinical-scientific interest

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75/80 and market, in the forms: cream, gel, vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, programmed-release tablets, oral tablets.

[161] - (018) - MINOXIDIL AND DRUG ASSOCIATIONS for the treatment of female and male sexual dysfunctions MINOXIDIL IN THE CONCENTRATIONS OF (0.01% TO 30%) CHARACTERIZED FOR BEING ASSOCIATED WITH OXYTOCIN (0.01 UI AT 50 IU ), indicated to improve the feeling of trust between the couple, feeling of attachment between partners, increased sexual interaction, improves the quality of orgasmic capacity, improves the capacity and erective quality, increased sexual arousal, increases the need to be held after sexual intercourse, increased intimacy between the couple, reduction of body widespread pain (sexual psychosomatization) including dyspareunias without organic etiologies, indicated for women with low quality or anorgastic orgasm, improvement of sexual arousal in both sexes, indicated for reduction vaginal lubrication. They can be produced or not, according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets, oral tablets.

[162] - (019) - MINOXIDIL AND DRUG ASSOCIATIONS for the treatment of female and male sexual dysfunctions, MINOXIDIL IN THE CONCENTRATIONS OF

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76/80 (10.1% to 30%) CHARACTERIZED FOR BEING IN ISOLATED FORM, indicated for cases of erectile dysfunction not responsive to other dosages of minoxidil with lower concentrations, increased sexual arousal in women, improvement of orgastic capacity in women, erectile dysfunction in diabetics unresponsive to minoxidil with lower concentrations, indicated, local genital use, in patients prevented from using Sildenafil, Vardenafil, Tadalafil and or nitrates, after negative exercise test, evaluation and indication by the attending physician. They can be produced or not, according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets, oral tablets.

[163] - (020) - MINOXIDIL AND DRUG ASSOCIATIONS for the treatment of female and male sexual dysfunctions MINOXIDIL IN THE CONCENTRATIONS OF (0.01% TO 08%) CHARACTERIZED BY THIS IN ISOLATED FORM, indicated for cases of dysfunction erectile that there is a therapeutic need for lower concentrations, increased sexual arousal in women, improved orgastic capacity in women, erectile dysfunction in diabetics unresponsive to minoxidil with dosages of different concentrations, indicated for local genital use, in patients prevented from using Sildenafil, Vardenafil, Tadalafil and or nitrates, after negative exercise test, evaluation and indication by the attending physician. They can be produced or not, according to the clinical-scientific interest 870180073364, of 08/21/2018, p. 91/99

77/80 market and individual, in the forms: cream, gel, vaginal ova, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets, oral tablets.

[164] - (021) - OXYTOCINA (0.01 IU TO 3 IU) in an ISOLATED way indicated to improve the feeling of trust between the couple, feeling of attachment between partners, increased sexual desire, improves the quality of orgasmic ability , improved erective capacity, increased sexual arousal, increased need to be embraced after sexual intercourse, increased intimacy between the couple,), indicated for women with low quality or anorgastic orgasm, improved sexual arousal in both sexes , reduction of body widespread pain (Sexual Psychosomatisation. They can be produced or not, according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal ova, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, programmed-release tablets, oral tablets [165] - (022) - OXYTOCIN IN ISOLATED FORM in the concentrations of (6UI TO 50 IU) indicated for improving the feeling of trust between the couple, feeling of attachment between partners, increased sexual desire, improves the quality of orgasmic capacity, improves erective capacity, increased sexual arousal, increases the need to be held after the sexual act, increased intimacy between the

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78/80 couple,), indicated for women with low quality or anorgastic orgasm, improvement of sexual arousal in both sexes, reduction of body widespread pain (Sexual Psychosomatisation. They can be produced or not, according to the clinical-scientific interest and market, in the forms: cream, gel, vaginal ova, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets, oral tablets [166] - (023 ) - MIINOXIDIL AND DRUG ASSOCIATIONS for the treatment of female and male sexual dysfunctions, MINOXIDIL (0.01 to 30%) CHARACTERIZED BY BEING ASSOCIATED WITH MELATONIN (0.1 MG TO 60 MG), improved sexual desire, improved quality orgasmic, improvement in sleep quality after orgasm, insomnia due to not having ideal sexual activity for the person, they can be produced or not, according to the clinical-scientific and market interest, under the ormas: cream, gel, vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets, oral tablets.

[167] - (024) - MINOXIDIL AND DRUG ASSOCIATIONS for the treatment of female and male sexual dysfunctions, MINOXIDIL IN THE CONCENTRATIONS OF (0.01% TO 30%) CHARACTERIZED FOR BEING ASSOCIATED WITH 17 BETA - ESTRADIOL (0.01 MG to 10 MG) indicated for women with orgastic difficulties, without gynecological pathologies,

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79/80 anorgasmia without prolactinomas or hyperprolactinemia, improved arousal capacity, reduced time to reach orgasm, indicated in low vaginal lubrication, indicated for sexual difficulties in female climacteric, women with hypoestrogenism and low libido, hypoestrogenism and vaginal dryness, dyspareunias due to vaginal dryness. They can be produced or not, according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets, oral tablets.

[168] - (026) - PRESENTATIONS - An aspect of differential and innovation in this patent is the fact that we are claiming in addition to the compounds above, all forms of presentations listed below, for these products, which may or may not be industrialized and commercialized for a given product or not, depending on clinical, market, commercial and industrial interest. Such claimed presentations are: cream, gel, solution, vaginal eggs, vaginal creams, ointment, nasal spray, sublingual spray, vaginal spray, liquid, aerosol, sublingual tablets, scheduled release tablets, oral tablets, transdermal and intradermal, IV injectables, IM injectables and IM injectables with scheduled release.

[169] - Such drug associations, even in the forms of claimed presentations, do not present state of the art, which gives them a single inventive concept,

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80/80 novelty, inventive step and industrial applicability and new scientific and therapeutic indications for patients with one or more concomitant sexual dysfunction.

[170] - In view of the above, I request that you issue the Certificate of the claimed Patent.

Claims (13)

MINOXIDIL ASSOCIATED WITH SEVERAL DRUGS AND USE OF OXYTOCIN TO TREAT FEMALE AND MALE SEXUAL DYSFUNCTIONS. [001] - MINOXIDIL AND DRUG ASSOCIATIONS FOR THE TREATMENT OF FEMALE AND MALE Sexual Dysfunctions CHARACTERIZED BY MINOXIDIL IN THE CONCENTRATIONS OF (0.01% TO 30%) ASSOCIATED WITH (DHEA) - DEHIDROEPIANDROSTERONE (0.1 MG A150 MG) indicated for woman's orgasmic difficulty, anorgasmia, improved sexual desire, excitatory difficulty, improved vaginal lubrication, dyspareunia due to low sexual arousal, improved sexual disposition in women and for the male population the indication consists of cases of erectile dysfunction, improved performance sexual in so-called normal men; men with hypoactive desire, diabetic patients and with vascular changes DIFFERENT FROM THE STATE OF THE TECHNIQUE reduced libido in both sexes; can be produced or not, according to the clinical-scientific and commercial market interest in the form of cream, gel, vaginal ova, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets and oral tablets. [002] - MINOXIDIL and DRUG ASSOCIATIONS for the treatment of FEMALE SEXUAL DYSFUNCTIONS CHARACTERIZED FOR BEING MINOXIDIL IN THE CONCENTRATIONS OF (0.01% TO 30%) ASSOCIATED WITH (DHEA) - DEHIDROEPIANDROSTERONE (0.1 MG to 150 MG) and also CHARACTERIZED FOR BEING ASSOCIATED with 17- B - ESTRADIOL (0.1 MG A15 MG) indicated for the treatment of women's orgastic difficulties, anorgasmia, improvement of sexual desire, improvement Petition 870180073364, of 8/21/2018, p. 3/99 2/13 vaginal lubrication, increased sexual stimulation, vaginal dryness, vaginismus, dyspareunia due to low vaginal lubrication and reduced sexual activity in the pre, menopause and post-menopause phases, in short, improved sexual disposition in both sexes, women carriers of hypoestrogenism and libido reduction, which can be produced or not, according to the clinical-scientific and commercial market interest, in the forms of cream, gel, vaginal ova, vaginal creams, ointment, nasal spray, vaginal spray, spray sublingual, liquid, aerosol, sublingual tablets, scheduled release tablets and oral tablets. [003] - MINOXIDIL and ASSOCIATIONS DRUGS TO TREAT FEMALE AND MALE SEXUAL DYSFUNCTIONS, CHARACTERIZED FOR BEING MINOXIDIL IN THE CONCENTRATIONS OF (0.01% TO 30%) CHARACTERIZED FOR BEING ASSOCIATED WITH TESTOSTERONE (0.1 MG A1000 MG), indicated for activation of sexual desire in men and in women, such as erectile dysfunction with low libido, erectile dysfunction, delayed ejaculation, sexual hypoactivity in both sexes, orgasmic difficulty in women, anorgasmia, improved vaginal lubrication, dyspareunia due to low vaginal lubrication and reduced sexual desire in both sexes, which can be produced or not, according to clinical-scientific and commercial market interest, in the form of cream, gel, vaginal ova, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets and oral tablets. [004] - MINOXIDIL and ASSOCIATIONS DRUGS for the treatment of FEMALE SEXUAL DYSFUNCTIONS CHARACTERIZED BY MINOXIDIL IN THE CONCENTRATIONS OF (0.01% to 30%) TO BE ASSOCIATED with TESTOSTERONE (0.1 MG Petition 870180073364, of 8/21/2018, p. 4/99 3/13 to 1000 MG) and also CHARACTERIZED FOR being ASSOCIATED with 17B-ESTRADIOL (0.01 MG to 10 MG), clinically indicated for the treatment of women with orgasmic difficulty in women and anorgasmia without hyperprolactinemia and / or in cases of prolactinoma without surgical or refractory indication in the sexual sphere after pituitary transfenoidal surgery, hypoactive desire in women undergoing menacme and menopause, improved vaginal lubrication, improved orgastic capacity, idiopathic vaginismus, dyspareunia due to low vaginal lubrication, dyspareunia due to hypoestrogenism and reduced libido, delayed ejaculation in men, which can be produced or not, according to the clinical-scientific and market interest, in the forms of cream, gel, vaginal ova, vaginal creams, ointment, nasal spray, vaginal spray , sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets and oral tablets. [005] - MINOXIDIL AND DRUG ASSOCIATIONS for the treatment of female and male sexual dysfunctions, CHARACTERIZED BY MINOXIDIL IN THE CONCENTRATIONS OF (0.01% TO 30%) ASSOCIATED WITH PHENYLALANINE (0.1 MG / DL to 5.0 MG / DL) or CHARACTERIZED FOR BEING ASSOCIATED with (L-PHENYLALANINE 10%) in the forms of cream, ointment, nasal spray, sublingual, aerosol, sublingual tablets, long-acting and programmed tablets, indicated for the treatment of men and women with low libido, patients with chronic bodily pain and sexual difficulties (sexual psychosomatization), women with idiopathic or psychogenic dyspareunias, idiopathic vaginismus, anorgasmia, orgasmic difficulty for women, improved sexual disposition in both sexes; patients with depression and sexual disinterest, hypoactive desire, delayed ejaculation, erectile dysfunction in patients with depression, which can be produced or not, according to the Petition 870180073364, of 8/21/2018, p. 5/99 4/13 clinical and scientific interest in the form of cream, gel, vaginal ova, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets and oral tablets . [006] - MINOXIDIL and DRUG ASSOCIATIONS for the treatment of FEMALE AND MALE sexual dysfunctions, CHARACTERIZED BY MINOXIDIL BEING IN THE CONCENTRATIONS OF (0.01% to 30%) AND BE ASSOCIATED WITH MELATONIN (0.1 MG to 60 MG), indicated for treatment of low libido in both sexes, improvement of sexual performance, improvement of the reduction of orgasmic fullness, improvement of the quality of sleep and sexual disposition, which can be produced or not, according to the clinical-scientific and market interest , in the forms of cream, gel, vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets and oral tablets. [007] - MINOXIDIL AND DRUG ASSOCIATIONS for the treatment of FEMALE AND MALE sexual dysfunctions CHARACTERIZED for being MINOXIDIL IN THE CONCENTRATIONS OF (0.01% to 30%) and being ASSOCIATED with BROMOCRIPTIN (0.01 MG to 100 MG) indicated in cases hypoactive desire with hyperprolactinemia in both sexes, erectile dysfunction in men with hypoactive desire due to hyperprolactinemia and or non-surgical prolactinoma, erectile dysfunction due to hyperprolactinemia, erectile dysfunction and / or low libido in the post pituitary transfenoidal surgery, anorgasmia and orgasmic difficulty hyperprolactinemia, which can be produced or not, according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal ova, vaginal creams, ointment, spray on Petition 870180073364, of 8/21/2018, p. 6/99 5/13 salt, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets and oral tablets. [008] - MINOXIDIL AND DRUG ASSOCIATIONS for Treatment of FEMALE AND MALE sexual dysfunctions CHARACTERIZED FOR BEING MINOXIDIL IN THE CONCENTRATIONS OF (0.01% to 30%) and being ASSOCIATED with APOMORFINE (0.1 MG to 20 MG), indicated for treatments of men with erectile dysfunction, erectile dysfunction with hypoactive desire, delayed ejaculation, anaejaculation, hypoactive desire in women, orgasmic difficulty in women, female anorgasmia in cases of not having prolactinoma or hyperprolactinemia, improved vaginal lubrication, difficulty with sexual arousal, improved libido, which can be produced or not, according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol , sublingual tablets, scheduled release tablets and oral tablets. [009] - MINOXIDIL AND DRUG ASSOCIATIONS for the treatment of FEMALE AND MALE sexual dysfunctions CHARACTERIZED FOR BEING MINOXIDIL IN THE CONCENTRATIONS OF (0.01% to 30%) AND BE ASSOCIATED WITH PROSTAGLANDIN - PG1 (1 MCG to 500 MCG) indicated for dysfunction erectile, improvement of sexual arousal in both sexes, female anorgasmia, orgasm difficulty for women and reduced vaginal lubrication, pain in the lower abdomen due to orgasm difficulty for women due to pelvic vascular congestion - interrupted orgasm), hypoactive desire, reduced vaginal lubrication , menopausal patients, who are clinically prevented from using Estrogens, for vaginal lubrication, can be produced or not, according to the clinical-scientific and market interest, under Petition 870180073364, of 8/21/2018, p. 7/99 6/13 the forms: cream, gel, vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets and oral tablets. [010] - MINOXIDIL and MEDICAL ASSOCIATIONS for the treatment of FEMALE AND MALE sexual dysfunctions CHARACTERIZED FOR BEING MINOXIDIL IN THE CONCENTRATIONS OF (0.01% to 30%) AND BE ASSOCIATED WITH PERGOLIDA (0.01 MG to 10 MG) indicated in Patients with Parkson's disease in both sexes, such as erectile dysfunction, erectile dysfunction with hypoactive desire, hypoactive desire, orgasmic difficulty carriers, which can be produced or not, according to the clinical-scientific and market interest, forms: cream, gel, vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets and oral tablets. [011] - MINOXIDIL and DRUG ASSOCIATIONS for the treatment of FEMALE AND MALE sexual dysfunctions CHARACTERIZED FOR BEING MINOXIDIL IN THE CONCENTRATIONS OF (0.01% to 30%) AND BE ASSOCIATED WITH SILDENAFIL HYDROCHLORIDE (0.1 MG to 500MG) indicated for erectile dysfunction, delayed ejaculation, woman's orgasmic difficulty, improvement of vaginal lubrication, improvement of anorgasmia without etiology of prolactinoma or hyperprolactinemia, which can be produced or not, according to the clinical, scientific and market interest, in the forms: cream, gel , vaginal ova, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets and oral tablets. [012] - MINOXIDIL AND DRUG ASSOCIATIONS Petition 870180073364, of 8/21/2018, p. 8/99 7/13 for the treatment of FEMALE AND MALE sexual dysfunctions, CHARACTERIZED FOR BEING MINOXIDIL IN THE CONCENTRATIONS OF (0.01% to 30%) AND TO BE ASSOCIATED WITH TADALAFILA CHLORIDRATE (0.1 MG to 200MG) indicated for erectile dysfunction, reduction of vaginal lubrication, delayed ejaculation, woman's orgasmic difficulty, which can be produced or not, according to the scientific and clinical interest of the market, in the forms: cream, gel, vaginal ova, vaginal creams, ointment, nasal spray, spray vaginal, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets and oral tablets. [013] - MINOXIDIL and MEDICAL ASSOCIATIONS for the treatment of FEMALE AND MALE sexual dysfunctions CHARACTERIZED FOR BEING MINOXIDIL IN THE CONCENTRATIONS OF (0.01% to 30%) AND BE ASSOCIATED WITH THE VARDENAPHIL CHLORIDATE (0.1 MG to 200MG) indicated for woman's orgasmic difficulty, improvement of woman's orgasmic dysfunction, reduction of vaginal lubrication, delayed ejaculation and erectile dysfunction, which can be produced or not, according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal ova, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets and oral tablets. [014] - MINOXIDIL AND MEDICINE ASSOCIATIONS for the treatment of FEMALE AND MALE sexual dysfunctions CHARACTERIZED FOR BEING MINOXIDIL IN THE CONCENTRATIONS OF (0.01% to 30%) AND BE ASSOCIATED with IOIMBINE (1 MG - 50 MG) indicated for erectile dysfunction with hypoactive desire, reduced vaginal lubrication, delayed ejaculation, orgasmic difficulty of women with hypoactive desire, psychogenic erectile dysfunction, reduced libido, which can be Petition 870180073364, of 8/21/2018, p. 9/99 8/13 produced or not, according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets , scheduled release tablets and oral tablets. [015] - MINOXIDIL AND MEDICINE ASSOCIATIONS for the treatment of FEMALE AND MALE sexual dysfunctions CHARACTERIZED FOR BEING MINOXIDIL IN THE CONCENTRATIONS OF (0.01% to 30%) and being ASSOCIATED WITH GABA (0.1 MG to 600MG), indicated for premature ejaculation associated with erectile dysfunction, erectile dysfunction due to exaggerated anxiety, psychogenic erectile dysfunction, idiopathic vaginismus, woman's orgasmic difficulty, erectile dysfunction due to Fear of Performance, reduced vaginal lubrication, altered sexual performance in patients with bipolar disorder and reduction of sexual activity, bipolarity and vaginismus in these cases for genital use, which can be produced or not, according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal eggs, vaginal creams, ointment, spray nasal, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets and v tablets it was oral. [016] - MINOXIDIL and DRUG ASSOCIATIONS for the treatment of FEMALE AND MALE sexual dysfunctions CHARACTERIZED FOR BEING MINOXIDIL IN THE CONCENTRATIONS OF (0.01% to 30%) and BE ASSOCIATED with GABA (850 MG to 1500 MG) indicated for refractory sexual dysfunctions to lower concentrations, such as, premature ejaculation associated with erectile dysfunction, erectile dysfunction due to fear of sexual performance, idiopathic vaginismus, woman's orgasmic difficulty, patients with bipolar disorder and sexual difficulties, depression and hypersexuality with behavior Petition 870180073364, of 8/21/2018, p. 10/99 9/13 inappropriate sexual partner, which can be produced or not, according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal ova, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets and oral tablets. [017] - MINOXIDIL and DRUG ASSOCIATIONS for the treatment of FEMALE AND MALE sexual dysfunctions CHARACTERIZED FOR BEING MINOXIDIL IN THE CONCENTRATIONS OF (0.01% to 30%) AND BE ASSOCIATED WITH BETA-ENDORFINE (0.1% to 30%) indicated for idiopathic dyspareunias, psychogenic dyspareunias, improvement of the quality of orgasm, improvement of the quality of the post-orgasmic state, reduction of sexual anxiety in both sexes, improvement of the quality of sleep in the post-orgasmic moment, which may or may not be produced, according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal ova, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets and tablets orally. [018] - MINOXIDIL AND DRUG ASSOCIATIONS for the treatment of FEMALE AND MALE sexual dysfunctions being CHARACTERIZED because it is MINOXIDIL IN THE CONCENTRATIONS OF (0.01% to 30%) and BE ASSOCIATED WITH OXYTOCIN (0.01 IU to 50 IU), indicated to improve the feeling of trust between the couple, feeling of attachment between partners, increased sexual interaction, improves the quality of orgasmic capacity, improves the capacity and erective quality, increased sexual arousal, increases the need to be embraced after the sexual act, increased intimacy between the couple, reduction of body widespread pain (sexual psychosomatization) including dyspareunias Petition 870180073364, of 8/21/2018, p. 11/99 10/13 without organic etiologies, indicated for women with low quality or anorgastic orgasm, improvement of sexual arousal in both sexes, indicated for reduction of vaginal lubrication, which can be produced or not, according to the scientific and market interest , in the forms: cream, gel, vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets and oral tablets. [019] - MINOXIDIL for the treatment of FEMALE AND MALE Sexual Dysfunctions, being CHARACTERIZED for being MINOXIDIL IN THE CONCENTRATIONS OF (10.1% to 30%) CHARACTERIZED FOR being in ISOLATED form, indicated for cases of erectile dysfunction not responsive to others minoxidil dosages with lower concentrations, different from the STATE OF THE TECHNIQUE, to increase sexual arousal in women, improve orgastic capacity in women, erectile dysfunction in diabetics not responsive to minoxidil with lower concentrations, indicated for local genital use, also indicated for action local in patients prevented from using Sildenafil, Vardenafil, Tadalafil and or nitrates, after negative exercise test, evaluation and indication by the attending physician, which may or may not be produced, according to the clinical-scientific and market interest, in cream forms, gel, vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets and oral tablets. [020] - MINOXIDIL for the treatment of FEMALE AND MALE Sexual Dysfunctions CHARACTERIZED FOR being MlNOXIDIL IN THE CONCENTRATIONS OF (0.01% to 8%) in ISOLATED form, indicated for cases of erectile dysfunction that there is a need for therapeutic concentrations of lower concentrations of the STATE OF THE TECHNIQUE, increased sexual arousal in women, improved orgastic capacity in Petition 870180073364, of 8/21/2018, p. 12/99 11/13 women, erectile dysfunction in diabetic patients unresponsive to minoxidil with dosages of different STATE OF THE TECHNIQUE, indicated for local genital use, in patients prevented from using Sildenafil, Vardenafil, Tadalafil and or nitrates, after negative exercise test, evaluation and indication of the attending physician, which may or may not be produced, according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal ova, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets and oral tablets. [021] - OXYTOCINA (0.01 IU to 3 IU) CHARACTERIZED FOR being in the ISOLATED form indicated for improving the feeling of trust between the couple, feeling of attachment between the partners, increased sexual desire, improves the quality of orgasmic ability, improved erective capacity, increased sexual arousal in both sexes, increased need to be held after sex, increased sexual intimacy between the couple, suitable for women and men with low-quality or anorgastic orgasms, improved sexual arousal in both sexes, reduction of body widespread pain (Psychosomatization Sexual, which can be produced or not, according to the clinical and scientific interest of the market, in the forms: cream, gel, vaginal eggs, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets , scheduled release tablets and oral tablets. [022] - OXYTOCINA CHARACTERIZED FOR being in ISOLATED form in the concentrations of (6UIA50 IU) indicated to improve the feeling of trust between the couple, feeling of attachment between partners, increased sexual desire, improves the quality of orgasmic capacity, improves erective capacity, increased sexual arousal, increased need to be held after the act Petition 870180073364, of 8/21/2018, p. 13/99 12/13 sexual, increased intimacy between the couple,), indicated for women with low quality or anorgastic orgasm, improvement of sexual arousal in both sexes, reduction of body widespread pain (Sexual Psychosomatisation, which can be produced or not, from according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal ova, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, programmed-release tablets and tablets via oral. [023] - MINOXIDIL AND MEDICINE ASSOCIATIONS for the treatment of FEMALE AND MALE SEXUAL Dysfunctions CHARACTERIZED BY MINOXIDIL (0.01 to 30%) and ASSOCIATED with MELATONIN (0.1 MG to 60 MG) indicated for the improvement of sexual desire , improvement in orgasmic quality, improvement in post-orgasm sleep quality, insomnia due to non-ideal sexual activity for the person, which can be produced or not, according to the scientific and market interest, in the forms: cream, gel , vaginal ova, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets and oral tablets. [024] - MINOXIDIL AND DRUG ASSOCIATIONS for the treatment of FEMALE AND MALE SEXUAL Dysfunctions, CHARACTERIZED BY MINOXIDIL IN THE CONCENTRATIONS OF (0.01% TO 30%) AND ASSOCIATED WITH THE 17 BETA - ESTRADIOL (0.01 MG to 10 MG ) clinically indicated for women with orgasmic difficulty, without gynecological pathologies, anorgasmia without prolactinomas or hyperprolactinemia, improved arousal capacity, reduced time to reach orgasm, indicated in low vaginal lubrication, indicated for sexual difficulties in female climacteric, women with hypo Petition 870180073364, of 8/21/2018, p. 14/99 13/13 estrogenism and low libido, hypoestrogenism and vaginal dryness, dyspareunias due to vaginal dryness, which can be produced or not, according to the clinical-scientific and market interest, in the forms: cream, gel, vaginal eggs, vaginal creams , ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets and oral tablets. [025] - PRESENTATIONS: I claim all the PRESENTATION FORM below for the substances claimed above, such as: cream, gel, vaginal ova, vaginal creams, ointment, nasal spray, vaginal spray, sublingual spray, liquid, aerosol, sublingual tablets, scheduled release tablets and oral tablets.