RU2312665C2 - Novel rapidly acting pharmaceutical compositions containing compounds eliciting activity in sexual dysfunction and cacao powder and their using - Google Patents

Abstract

FIELD: medicine, sexology, biochemistry, pharmacy.

SUBSTANCE: invention discloses a rapidly acting pharmaceutical composition showing high bioavailability containing active compound in sexual dysfunction and not presenting chew elastic. Active compound is chosen from derivatives of compounds of the formula (I) or (II) given in the invention description, or compound chosen from inhibitors of phosphodiesterase type 5, such as sildenafil, vardenafil, tadalafil, or compound chosen from dopaminergic agonists, such as apomorphine, or compound chosen from noradrenergic α-antagonists, or compound chosen from activators of cyclic AMP with a addition of cacao powder as not component of chocolate for adequate taste masking, and one or more lipid components.

EFFECT: valuable biological properties of pharmaceutical compositions.

19 cl, 4 ex

Description

Field of Invention

This invention relates to new, fast-acting, orally administered pharmaceutical compositions of compounds active in sexual dysfunction (SD), and to their use. More specifically, the present invention relates to compositions containing SD compounds and cocoa powder, to methods for producing said compositions and methods for using said compositions in the treatment of sexual dysfunction, including increasing sexual desire, interest or function.

BACKGROUND AND BACKGROUND

Orally administered drugs in the case of sexual dysfunction, in particular with erectile dysfunction, are well known. See, for example, Gingell & Lockyer (1999), "Emerging pharmacological therapies for erectile dysfunction", Expert Opinion on Therapeutic Patents 9, 1689-1696. Medicines used or developed include phosphodiesterase type 5 inhibitors (PDE5), for example sildenafil citrate, available under the Viagra® trademark from Pfizer, cyclic AMP activators, α-adrenergic antagonists, for example yohimbine, and dopaminergic agonists, for example apomorphine.

International Patent Publication No. WO 00/40226 discloses compounds useful in the treatment of sexual dysfunction in men and women; moreover, these compounds have the formula (I)

or their pharmaceutically acceptable salts, where

R ¹ , R ² and R ³ are the same or different and are H, C _1-6 alkyl (optionally phenyl substituted), C _3-5 alkenyl or alkynyl or C _3-10 cycloalkyl, or where R ³ is as defined above, and R ¹ and R ^{2 are} cyclized with an attached N atom to form pyrrolidinyl, piperidinyl, morpholinyl, 4-methylpiperazinyl or imidazolyl;

X is H, F, Cl, Br, I, OH, C _1-6 alkyl or alkoxy, CN, carboxamide, carboxyl or (C _1-6 alkyl) carbonyl;

A is CH, CH ₂ , CHF, CHCl, CHBr, CHI, CHCH ₃ , C = O, C = S, CSCH ₃ , C = NH, CNH ₂ , CNHCH ₃ , CNHCOOCH ₃ , CNHCN, SO ₂ or N;

B is CH, CH ₂ , CHF, CHCl, CHBr, CHI, C = O, N, NH or NCH ₃ , and n is 0 or 1;

D is CH, CH ₂ , CHF, CHCl, CHBr, CHI, C = O, O, N, NH or NCH ₃ ;

under various specified conditions.

WO 00/40226 also considers the administration to patients (men and women) of the drug (R) -5,6-dihydro-5- (methylamino) -4H-imidazo [4,5-ij] quinolin-2 (1H) -one ( Z) -2-butenedioate (1: 1) at a dose of 1-3 mg to be taken 0.5-1 hour before sexual activity, and it is shown that at this dose and time of administration, the drug is therapeutically effective. No information is provided regarding the method of administration or type of dosage form.

The class of compounds proposed for the treatment of sexual dysfunction in WO 00/40226 was previously disclosed in US Pat. No. 5,273,975 (Moon et al.) As having a therapeutically beneficial activity on the central nervous system. Some compounds of the above class are the subject of a review by Heier et al. (1997), "Synthesis and biological activities of (R) -5,6-dihydro-N, N-dimethyl-4H-imidazo [4,5.1-ij] quinolin-5-amine and its metabolites", J. Med. Chem. 40, 639-646.

Despite the availability of sildenafil citrate, apomorphine, and other drugs in the form of orally delivered forms, there remains a need for dosage forms of a therapeutic agent for the treatment of sexual dysfunction in men and women with one or more of the following advantages:

(a) rapid absorption leading to a rapid manifestation of a therapeutic effect;

(b) reduced tastelessness;

(c) lack of need for intake with water;

(d) high bioavailability of substances with high presystemic metabolism;

(e) providing an association of pleasures and

(f) the absence of directly perceived patient association with drugs.

In one aspect, the sexual dysfunction in question here includes, but is not limited to: sexual dysfunction, impaired sexual arousal in women, erectile dysfunction in men, an orgasm disorder in women, and an orgasm disorder in men — all as defined in the Diagnostic and Statistical Manual of Mental Disorders, 4 ^th edition (DSM-IV) (1994) and DSM-IV Guidebook (1995), both published by American Psychiatric Press, Inc., Washington, DC.

In another aspect, the sexual dysfunction in question here includes a decrease in sexual desire, interest, and / or function resulting from primary diseases or conditions that are not literally sexual dysfunctions. Such diseases and conditions include, but are not limited to, epilepsy, craniopharyngioma, hypogonadism, and general psychiatric disorders such as depression. The sexual dysfunction in question here also includes sexual failure after a hysterectomy and / or ovariectomy (removal of the ovaries), as well as a result of side effects of drugs.

European Patent Application No. 0960621 discloses that sildenafil citrate has an unpleasant taste that cannot be completely masked by flavoring agents (flavoring agents) and offers rapidly disintegrating dosage forms for oral administration of sildenafil in the form of its free base, which has extremely low solubility in water and is almost tasteless .

International Patent Publication No. WO 99/66933 proposes the intranasal administration of sildenafil, for example, in the form of a salt, such as a hydrochloride salt, for the treatment of erectile dysfunction. Suggested dosage forms include a nasal spray and an aqueous nasal gel. It is indicated that aqueous solutions are preferred. The rapid manifestation of a therapeutic effect is considered; however, no solution is proposed to the problem of unpleasant taste that occurs when the drug is dissolved in the oral cavity. In addition, intranasal administration is not a sufficiently correct way to administer SD compounds. As provided in WO 99/66933, dose levels should be lower than required when the drug is administered orally; as an example, a dose of 30 mg sildenafil hydrochloride in the form of a nasal spray is given. A nasal spray preparation delivering 30 mg of sildenafil hydrochloride and 1 mg of apomorphine hydrochloride is also given as an example.

European Patent Application No. 0992240 discloses cGMP-PDE inhibitory compounds which are indicated to be useful in the treatment of erectile dysfunction in men and proposes the administration of such compounds through the mucous membrane, for example, in the form of sublingual preparations.

International Patent Publication No. WO 00/76509 also proposes the nasal administration of apomorphine, for example, in the form of its hydrochloride salt.

Heaton (1996), Buccal apomorphin, J. Urol. 155, 49, reports on the effectiveness of the sublingual drug apomorphine in the treatment of inorganic erectile dysfunction in men.

US patent No. 5985889 (El-Rashidy et al.) Proposes sublingual administration of apomorphine for the treatment of psychogenic erectile dysfunction in men. A variety of apomorphine hydrochloride preparations are disclosed in the form of sublingual tablets.

International Patent Publication No. WO 00/35457 proposes the use of apomorphine for the treatment of organic, for example, vasculogenous, erectile dysfunction in men and gives an example of the use of apomorphine hydrochloride as a sublingual tablet. WO 00/35457 also suggests that nausea, a common side effect of apomorphine, can be controlled by including an antiemetic agent such as nicotine in the preparation.

US patent No. 6121276 (El-Rashidy & Ronsen) discloses flavored sublingual tablets containing apomorphine hydrochloride and nicotine.

International Patent Publication No. WO 01/49292 discloses sublingual apomorphine tablets providing sustained release of a medicament useful as indicated in the treatment of Parkinson's disease.

International Patent Publication No. WO 00/42992 discloses a dosage unit containing a water-soluble hydrocolloid and sildenafil citrate in a mucoadhesive film suitable, as indicated, for use on the oral mucosa. The pharmacokinetic data presented in WO 00/42992 show the absence of faster absorption into the bloodstream with the sublingual use of such a film compared to the commercial tablet formulations of sildenafil citrate (Viagra®) at the same dosage.

International Patent Publication No. WO 01/10406 discloses compositions suitable as indicated for a wide variety of methods for administering sildenafil citrate, including buccal and sublingual methods. Preferred disclosed compositions are indicated to include a solution, gel, semi-solid preparation, suspension, dosage device, transdermal patch or film.

International Patent Publication No. WO 02/05820 discloses dosage forms in the form of films containing sildenafil citrate. These dosage forms are prepared by mixing a solid dispersion of sildenafil citrate and water soluble sugar with a hydrocolloid and optionally other ingredients, and as indicated, when coated on the mucous surface, they form a coating that then disintegrates and dissolves, releasing sildenafil.

International Patent Publication No. WO 02/041840 discloses the use of cocoa powder in chewing gums as a flavoring agent (flavor), but not a taste masking agent, for sildenafil citrate.

International Patent Publication No. WO 00/30641 discloses the use of cocoa powder as a flavoring agent in oral compositions containing nicotine.

International Patent Publication No. WO 99/66916 discloses the use of a chocolate flavoring agent (flavor) in oral compositions containing apomorphine.

Chocolate, which is very different from cocoa powder as such, is rarely used as an ingredient in pharmaceutical products sold, so far only in laxatives. One example is Ex-Lax®, a chocolate laxative sold by Novartis containing sennosides. Purex, a laxative in which phenolphthalein is made with chocolate, was sold in the 1950s.

It has now surprisingly been found that the rapid onset of orally administered pharmaceutical compositions of SD compounds is achieved by concomitantly masking the taste of poorly tasted ingredients such as buffering agents by using formulations containing SD compounds and cocoa powder as a masking filler / diluent taste or flavoring agent and agent to provide a uniform texture. So far, such drugs have not been disclosed.

Summary of invention

The present invention discloses an orally administered fast-acting pharmaceutical composition useful for treating sexual dysfunction, stimulating sexual activity and enhancing sexual desire, interest and function in men and women. The composition is a dosage form containing a therapeutically effective or sexually stimulating effective amount of one or more SD compounds. As used herein, the term “therapeutically effective amount” means an amount sufficient to enhance sexual desire, interest, or function in a subject having sexual dysfunction. As used herein, the term “sexually stimulating effective amount” means an amount sufficient to enhance sexual desire, interest, or function in a subject with or without sexual dysfunction.

Such suitable SD compounds are selected from, but not limited to, the following agents.

The compound of formula (I)

or its pharmaceutically acceptable salt, where

R ¹ , R ² and R ³ are the same or different and are H, C _1-6 alkyl (optionally phenyl substituted), C _3-5 alkenyl or alkynyl or C _3-10 cycloalkyl, or where R ³ is as described above and R ¹ and R ^{2 are} cyclized with an attached N atom to form a pyrrolidinyl, piperidinyl, morpholinyl, 4-methylpiperazinyl or imidazolyl group;

X is H, F, Cl, Br, I, OH, C _1-6 alkyl or alkoxy, CN, carboxamide, carboxyl or (C _1-6 alkyl) carbonyl;

A is CH, CH ₂ , CHF, CHCl, CHBr, CHI, CHCH ₃ , C = O, C = S, CSCH ₃ , C = NH, CNH ₂ , CNHCH ₃ , CNHCOOCH ₃ , CNHCN, SO ₂ or N;

B is CH, CH ₂ , CHF, CHCl, CHBr, CHI, C = O, N, NH or NCH ₃ , and n is 0 or 1;

D is CH, CH ₂ , CHF, CHCl, CHBr, CHI, C = O, O, N, NH or NCH ₃ ;

wherein said compound of formula (I) or a salt thereof is soluble in water. A suitable dose is from about 0.1 mg to about 10 mg per dose.

The compound of formula (II)

where X is O or S, and pharmaceutically acceptable salts thereof. A suitable dose is from about 0.05 mg to about 10 mg per dose.

A compound selected from type 5 phosphodiesterase inhibitors (PDE5), such as base sildenafil and its pharmaceutically acceptable salts, including sildenafil citrate sold under the trademark Viagra®, vardenafil sold as Nuviva, and tadalafil sold as Cialis®. A suitable dose is from about 5 mg to about 100 mg per dose.

A compound selected from dopaminergic agonists, such as apomorphine, with or without antiemetic agents. A suitable dose is from 0.5 mg to about 10 mg per dose.

A compound selected from noradrenergic alpha antagonists or alpha adrenergic antagonists such as phentolamine mesylate sold as Vasomax, yohimbine and prazosin.

A compound selected from cyclic AMP activators.

Pharmaceutically acceptable salts, complexes and mixtures of the above compounds are also useful.

Preferably, the amount of the SD compound, salt, complex or mixture thereof is lower than the amount causing significant side effects.

A particularly useful dosage form of the present invention is a preparation that disintegrates or melts in the mouth without having to wash it with water or another liquid.

Preferred dosage forms are tablets, sublingual tablets, and lozenges. Chewing gums are not preferred dosage forms.

This invention is adapted for correct self-administration. Here, “correct self-administration” is understood to mean self-admission shortly before sexual activity in a way that does not attract the attention of the sexual partner to, or does not emphasize, the presence of sexual dysfunction, the need for treatment, or the need or desire to increase sexual function. The combination of correctness and quick effect allowed by the present invention provides the advantage of spontaneity; in contrast, prior art compositions for treating sexual dysfunction can be seriously compromised in their effectiveness if their self-administration requires prior planning and / or cannot be performed correctly, thus such self-administration does not lead to spontaneity.

The present invention also provides methods of using the compositions of the present invention to treat sexual dysfunction and to enhance sexual desire, interest or function, and a method of using the composition of the present invention to produce a medicament. Other features of the present invention will be partially clear and partially indicated below.

Compositions for the therapeutic delivery of SD compounds are provided. These compositions containing SD compounds provide rapid absorption through the mucous membrane in the oral cavity.

SD compounds of the present invention include the parent forms, as well as salts and complexes of the parent forms.

The aim of this invention is the provision of new pharmaceutical compositions of SD compounds for buccal absorption or absorption by other mucous membranes in the oral cavity, in particular such compositions containing a large percentage of cocoa powder.

A second object of the present invention is to provide methods for preparing said compositions.

A third object of the present invention is methods of using said drugs in the treatment of sexual dysfunction, including increasing sexual desire, interest or function.

Additional objectives of the present invention will be clear to a person skilled in the art, and yet other objectives will be clear from the description and claims.

The main advantages provided by the composition according to the present invention are the following:

1) it makes possible the rapid appearance of a pharmacological effect;

2) it provides good taste masking properties due to the presence of cocoa powder;

3) it does not require water to swallow;

4) it provides the highest possible bioavailability of substances with high presystemic metabolism;

5) it provides an association of pleasant sensations;

6) it does not give the patient directly perceived association with drugs (traditional tablets).

DETAILED DESCRIPTION OF THE INVENTION

The main objective of the present invention is the provision of high-speed pharmaceutical compositions useful for the treatment of sexual dysfunction, stimulation of sexual activity and increase sexual desire, interest or function in men and women. The term "fast acting" means that the therapeutic effect is achieved in a short period of time, for example, in less than about 1 hour, preferably in less than 30 minutes, after administration.

More specifically, it is an object of the present invention to provide such a composition containing an SD compound for mucosal delivery, preferably for buccal delivery, which disintegrates and / or melts at body temperature, with or without salivary fluid or mechanical disruption or a combination thereof, after wherein the composition preferably exhibits adhesion to tissues in the oral cavity.

The addition of buffering agents provides a short-term change in the local pH of saliva. Thus, a higher proportion of the active agent is transformed into a less ionized form. This facilitates penetration through the mucous membranes, which increases the absorption of the active agent. For a person skilled in the art it is obvious that the choice of a buffer system depends on one or more pKa of the active agent.

Surprisingly, it has been found that by using cocoa powder, rapid buccal absorption of SD compounds is achieved, accompanied by a sufficient masking of the taste of the poorly tasted ingredients, such as the active compound and / or buffering agents. Cocoa powder acts as a filler / diluent, as well as a taste masking agent or flavoring agent and as an agent to provide a uniform texture. So far, no similar drugs have been disclosed.

A preferred formulation is a composition weighing about 400-500 mg, having the following ingredients:

a therapeutically effective amount of an SD compound,

cocoa powder - about 200 mg,

fatty components - approximately 180 mg,

aspartame - about 2.5 mg,

sodium carbonate - about 15 mg

lecithin - approximately 4 mg.

Preferably, the composition will include at least 15 wt.% Cocoa powder.

Cocoa powder is defined as crushed cocoa beans, from which a certain amount of fat is removed and which are crushed into powder. Crushed cocoa beans are defined as cocoa beans from which the husk is removed. Cocoa butter is defined as fat squeezed from the center (kernels or crushed cocoa beans) of cocoa beans.

Cocoa powder is obtained from roasted cocoa beans. It represents a complex of compounds that includes starch, cocoa butter, amino acids, proteins, xanthines, amines, mono- and polysaccharides, phospholipids, flavonoids, pyrazines, etc.

Preferred fatty components are fats / lipids selected from tempered fats, including cocoa butter equivalents (CBE) and cocoa butter improvers (CBI), and non-tempered fats, including cocoa butter substitutes (CBR) and cocoa butter substitutes (CBS).

According to Industrial Chocolate Manufacture and Use, ST Beckett, ed., 2 ^nd edition, Blackier Academic & Professional, London, 1994, p. 382, chocolate is defined as a product obtained from crushed cocoa beans, cocoa powder and sucrose with or without cocoa butter, having a minimum dry cocoa solids content of 35%, at least 14% dry cocoa solids and 18% cocoa butter. Chocolate has two main distinguishing characteristics: its taste and texture. The main feature of the texture is that the chocolate should be solid at a temperature of 20-25 ° C and quickly melt in the mouth already at 37 ° C, turning into a liquid that seems uniform in the tongue. Chocolate processing refers to the receipt of these two criteria (ibid., P. 2).

Neither milk chocolate, nor light chocolate for cooking, nor dark chocolate for cooking can mask the unpleasant taste of most buffering agents. The cocoa content in milk chocolate is relatively low (the content of cocoa mass is 10-16%, which corresponds to about 5-8% of cocoa powder). The content of beans / cocoa mass in dark, bittersweet chocolate is 55-70% (Beckett, pp.276-277), which corresponds to approximately 28-35% of cocoa powder. Obtaining a carrier with a high content of cocoa powder (30-70%) and fatty components (30-50%), which corresponds to the present invention, nevertheless receive an effective masking. The higher the concentration of cocoa powder, the better the masking of taste.

Examples

The following are non-limiting examples of the preparation of certain embodiments of the present invention.

Example 1: Getting the preferred option

A composition weighing about 400 mg, having the following preferred composition (wt./wt.):

active ingredient: SD compound corresponding to the above formula (I) in an amount of from about 0.25 mg to about 10 mg diluent / filler, flavoring / taste masking agent and an agent to provide a uniform texture: cocoa powder, approximately 50% lipid ingredient: cocoa butter equivalents (CBE), approximately 44% buffering agent sodium carbonate, approximately 4% sweetener aspartame, approximately 0.6% emulsifier / solubilizer lecithin, approximately 1% flavoring agent: mint or vanilla 0.5%

receive as follows:

Part of the CBE is melted. Solid components are added, i.e. SD compound, cocoa powder, aspartame, sodium carbonate and flavoring agent, if solid, and mixed. Particles of solid components are ground by grinding them in a roller mill. If the solid components have already obtained the required particle size, for example, by grinding before mixing with the fat components, then they do without a roller mill. After processing in a roller mill, the mixture is mixed with the remainder of the molten fatty components or re-melted (if cured) and mixed with the remainder of the molten CBE. Mixing of the melt is carried out in a suitable mixer. Liquid components are added, i.e. lecithin and a flavoring agent if it is liquid. Then tablets or other solid dosage forms are prepared using suitable techniques, such as molding, extrusion, or hardening, including making lozenges, if necessary, after appropriate preconditioning. Other suitable manufacturing methods may also be used.

Example 2: Getting another option

Essentially the same way as in example 1, get a composition weighing from about 400 mg to about 500 mg, containing the following ingredients:

0.25 mg to about 10 mg of the compound of the above formula (II),

about 50% (w / w) cocoa powder,

about 44% (w / w) cocoa butter equivalents (CBE),

about 4% (w / w) sodium carbonate,

about 0.6% (w / w) aspartame and / or acesulfamecal and about 1% (w / w) lecithin.

Example 3: Getting another option

Essentially in the same way as in example 1, get the composition of the following composition:

active ingredient: Therapeutically sufficient SD compound diluent / filler, flavoring / taste masking agent, and a uniform texture agent cocoa powder and optionally a small amount of a substance / substances selected from one or more compounds: fructose, glucose, galactose, invert sugar, a pharmaceutically acceptable polyol such as xylitol, sorbitol, maltitol, mannitol, isomalt and glycerin, or polydextrose or any mixture thereof from about 30 to about 70% (w / w) lipid ingredient from about 30 to about 50% (w / w) buffering agent from 0 to about 10% (w / w) sweetener from about 0.3 to about 3% (w / w) emulsifier / co-mobilizer from about 0.3 to about 5% (w / w) flavoring agent from 0 to about 4% (w / w)

Example 4: Obtaining Alternatives

Useful options are obtained by replacing certain excipients in the variations of the above examples with equivalent active alternative compounds.

A small portion of the cocoa powder can be replaced by one or more of the following compounds: fructose, glucose, galactose, lactose, maltose, invert sugar, a pharmaceutically acceptable polyol such as xylitol, sorbitol, maltitol, mannitol, isomalt and glycerin or polydextrose, or any mixture thereof but only to the extent that the effect of the cocoa powder, masking the taste, remains sufficient.

The lipid ingredient, being a fatty component, can be selected from one or more of the following compounds:

- cocoa butter and alternatives to cocoa butter substances, including cocoa butter equivalents (CBE), cocoa butter substitutes (CBS), cocoa butter substitutes (CBR) and cocoa butter improvers (CBI);

- coconut, palm kernel oil and other similar oils, characterized in that they are based mainly on lauric and myristic acids;

- palm oil, butter tree oil, shea butter (karite), bassia butter, mango seed oil, sal fat (Shorea Robusta) and other similar fats, characterized in that they are based mainly on palmitic, oleic and stearic acids;

- corn oil, sunflower oil, hybrid sunflower oil, soybean oil, rapeseed oil, canola oil, olive oil, rice oil, cottonseed oil, peanut (peanut, groundnut) oil and other oils characterized in that they are based mainly on oleic, linoleic and linolenic acids, and they are hydrogenated to obtain a suitable melting point;

- fish oil, lard, lard, oil fat and other animal fats, and

- synthetic fats, transesterified fats, solid fats obtained by the chemical interaction of fatty acids with glycerin without the use of acid, alkaline or enzymatic catalysts,

wherein said compound (s) are used as the sole component or in a mixture with each other, whether raw or purified using physical or alkaline purification, or by further processing, including catalytic hydrogenation, transesterification, transesterification and fractionation.

Sodium carbonate buffer can be replaced with carbonates, bicarbonates, acetates, gluconates, glycerophosphates, phosphates or glycinates of sodium, potassium or ammonium, or mixtures thereof. Most phosphates are considered the least suitable, as they usually have an unpleasant taste and are difficult to mask.

The aspartame sweetener can be fully or partially replaced with one or more other artificial sweeteners, such as acesulfamecal, saccharin, sodium saccharin, cyclamate and glycyrrhizin and / or their salts.

The emulsifier lecithin is preferably soya lecithin and / or egg lecithin, but may be replaced

- a non-ionic surfactant such as poloxamer, polyoxyethylene alkyl ester, castor oil polyoxyethylene derivative, polyoxyethylene sorbitan fatty acid esters, monoglyceride, diglyceride and their esters, polyoxyethylene stearate, polyglycerol fatty acid esters (including polyglycerol ether acids fatty acids;

an anionic surfactant such as fatty acid, fatty acid soap, lactylate, in particular sodium and / or calcium steroylactylate, sodium lauryl sulfate and latanol;

a zwitterionic surfactant such as a zwitterionic phospholipid, for example phosphatidylcholine and phosphatidylethanolamine or

- their mixtures, fractions, or derivatives, or mixtures, fractions or derivatives of these compounds with lecithin.

In essentially the same way as in the above examples, it is possible to obtain compositions containing other SD compounds. In such cases, the dose range and the percentage of excipients should be adjusted accordingly.

Claims (19)

1. A fast-acting oral pharmaceutical composition in a dosage form that is not a chewing gum, containing a compound (s) active (active) for sexual dysfunction, characterized in that it contains cocoa powder in an amount of at least 15%, not present as a chocolate component, and one or more lipid ingredients, wherein the compound (s) active (active) for sexual dysfunction are selected (selected) from the following compounds: compound of formula (I)

or its pharmaceutically acceptable salt, where R ¹ , R ² and R ^{3 are the} same or different and are H, C _1-6 alkyl (optionally phenyl substituted), C _3-5 alkenyl or alkynyl or C _3-10 cycloalkyl, or where R ³ is as described above, and R ¹ and R ^{2 are} cyclized with an attached N atom to form a pyrrolidinyl, piperidinyl, morpholinyl, 4-methylpiperazinyl or imidazolyl group; X is H, F, Cl, Br, I, OH, C _1-6 alkyl or alkoxy, CN, carboxamide, carboxyl or (C _1-6 alkyl) carbonyl; A is CH, CH ₂ , CHF, CHCl, CHBr, CHI, CHCH ₃ , C = O, C = S, CSCH ₃ , C = NH, CNH ₂ , CNHCH ₃ , CNHCOOCH ₃ , CNHCN, SO ₂ or N; B is CH, CH ₂ , CHF, CHCl, CHBr, CHI, C = O, N, NH or NCH ₃ , n is 0 or 1; D is CH, CH ₂ , CHF, CHCl, CHBr, CHI, C = O, O, N, NH or NCH ₃ ; wherein said compound of formula (I) or a salt thereof is soluble in water; compound of formula (II)

where X is O or S, and pharmaceutically acceptable salts thereof; a compound selected from type 5 phosphodiesterase inhibitors (PDE5), such as sildenafil in the form of a base and its pharmaceutically acceptable salts, including sildenafil citrate, vardenafil and tadalafil; a compound selected from dopaminergic agonists, such as apomorphine, optionally with antiemetic agents; a compound selected from noradrenergic alpha antagonists or alpha adrenergic antagonists such as phentolamine mesylate, yohimbine and prazosin; a compound selected from cyclic AMP activators; and their pharmaceutically acceptable salts, complexes and mixtures. 2. The composition according to claim 1, characterized in that it further comprises one or more buffering agents. 3. The composition according to claim 2, characterized in that one or more buffering agents are selected from carbonates, bicarbonates, acetates, gluconates, glycerophosphates, phosphates or glycinates of sodium, potassium or ammonium, or mixtures thereof. 4. The composition according to claim 1, characterized in that it further comprises one or more sweeteners and optionally one or more flavoring agents. 5. The composition according to claim 4, characterized in that one or more sweeteners are aspartame, acesulfamecal, saccharin, sodium saccharin, cyclamate and / or glycyrrhizin and / or their salts. 6. The composition according to claim 1, characterized in that one or more lipid ingredients selected from the following: cocoa butter and alternatives to cocoa butter substances, including cocoa butter equivalents (CBE), cocoa butter substitutes (CBS), cocoa butter substitutes (CBR) and improvers for cocoa butter (CBI); coconut, palm kernel oil and other similar oils, characterized in that they are based primarily on lauric and myristic acids; palm oil, shea butter, shea butter, bassia walnut oil, mango seed oil, sal fat (Shorea Robusta) and other similar fats characterized in that they are based primarily on palmitic, oleic and stearic acids; corn oil, sunflower oil, hybrid sunflower oil, soybean oil, rapeseed oil, canola oil, olive oil, rice oil, cottonseed oil, peanut (peanut) oil and other oils characterized in that they are based primarily on oleic, linoleic and linolenic acids and they are hydrogenated to a suitable melting point; fish oil, lard, lard, oil oil and other animal fats, and synthetic fats, interesterified fats, solid fats obtained by the chemical interaction of fatty acids with glycerin without the use of acid, alkaline or enzymatic catalysts; wherein said compound (s) are used as the sole component or in a mixture with each other, whether raw or purified using physical or alkaline purification, or by further processing, including catalytic hydrogenation, transesterification, transesterification and fractionation. 7. The composition according to claim 6, characterized in that one or more lipid ingredients are selected from cocoa butter equivalents (CBE), cocoa butter substitutes (CBS) and cocoa butter substitutes (CBR). 8. The composition according to claim 1, characterized in that it further comprises one or more emulsifiers / solubilizers. 9. The composition of claim 8, wherein one or more emulsifiers / solubilizers selected from the following lecithin, preferably soya lecithin and / or egg lecithin; nonionic surfactant such as poloxamer, polyoxyethylene alkyl ester, castor oil polyoxyethylene derivative, polyoxyethylene sorbitan fatty acid esters, monoglyceride, diglyceride and their esters, polyoxyethylene stearate, polyglycerol fatty acid esters (including polyglycerol fatty acid) acids; an anionic surfactant such as fatty acid, fatty acid soap, lactylate, in particular sodium and / or calcium steroylactylate, sodium lauryl sulfate and latanol; a zwitterionic surfactant, such as a zwitterionic phospholipid, for example, phosphatidylcholine and phosphatidylethanolamine, or mixtures thereof, fractions or derivatives, or mixtures, fractions, derivatives of these lecithin compounds. 10. The composition according to claim 9, characterized in that one or more emulsifiers / solubilizers selected from lecithin, preferably soya lecithin and / or egg lecithin. 11. The composition according to claim 1, characterized in that it further comprises a small amount of a substance / substances selected from one or more substances: fructose, glucose, galactose, lactose, maltose, invert sugar, a pharmaceutically acceptable polyol such as xylitol, sorbitol, maltitol, mannitol, isomalt and glycerin, or polydextrose, or any mixture thereof. 12. The composition according to claim 1, characterized in that its unit dose contains the active ingredient: a compound active in sexual dysfunction in a therapeutically sufficient amount; diluent / filler; flavoring / taste masking agent and an agent for providing a uniform texture: cocoa powder and optionally a small amount of a substance / substances selected from one or more substances: fructose, glucose, galactose, invert sugar, a pharmaceutically acceptable polyol such as xylitol sorbitol, maltitol, mannitol, isomalt and glycerin, or polydextrose, or any mixture thereof, from about 30 to about 70% (w / w); lipid ingredient: from about 30 to about 50% (w / w); buffering agent: from 0 to about 10% (w / w); sweetener: from about 0.3 to about 3% (w / w); emulsifier / solubilizer: from about 0.3 to about 5% (w / w); flavoring agent: from 0 to about 4% (w / w). 13. The composition according to p. 12, characterized in that its unit dose contains from 0.25 mg to about 10 mg of the compound of formula (II)

where X is O or S, and its pharmaceutically acceptable salts; about 50% (w / w) cocoa powder, about 44% (w / w) cocoa butter equivalents (CBE), about 4% (w / w) sodium carbonate, about 0.6% (w / w) aspartame and / or acesulfamecal and about 1% (w / w) lecithin. 14. The composition according to p. 12, characterized in that its unit dose contains active ingredient: compound active in sexual dysfunction, formula (I)

or its pharmaceutically acceptable salt, where R ¹ , R ² and R ^{3 are the} same or different and are H, C _1-6 alkyl (optionally phenyl substituted), C _3-5 alkenyl or alkynyl or C _3-10 cycloalkyl, or where R ³ is as described above, and R ¹ and R ^{2 are} cyclized with an attached N atom to form a pyrrolidinyl, piperidinyl, morpholinyl, 4-methylpiperazinyl or imidazolyl group; X is H, F, Cl, Br, I, OH, C _1-6 alkyl or alkoxy, CN, carboxamide, carboxyl or (C _1-6 alkyl) carbonyl; A is CH, CH ₂ , CHF, CHCl, CHBr, CHI, CHCH ₃ , C = O, C = S, CSCH ₃ , C = NH, CNH ₂ , CNHCH ₃ , CNHCOOCH ₃ , CNHCN, SO ₂ or N; B is CH, CH ₂ , CHF, CHCl, CHBr, CHI, C = O, N, NH or NCH ₃ , n is 0 or 1; D is CH, CH ₂ , CHF, CHCl, CHBr, CHI, C = O, O, N, NH or NCH ₃ ; in an amount of from about 0.25 mg to about 10 mg; diluent / filler, flavoring / taste masking agent and an agent for providing a uniform texture: cocoa powder about 50%; lipid ingredient: cocoa butter equivalents (CBE), about 44%; buffering agent: sodium carbonate, about 4%; sweetener: aspartame, about 0.6%; emulsifier / solubilizer: lecithin, about 1%; flavoring agent: mint or vanilla flavor 0.5%. 15. The composition according to claim 1, which is prepared as a dosage form for oral administration and ensures the delivery of compounds active in sexual dysfunction through the buccal mucosa and / or other oral mucosa. 16. The composition according to claim 1, which is prepared in the form of tablets, sublingual tablets or lozenges. 17. The use of a composition according to any one of the preceding paragraphs for the manufacture of a medicament useful for treating sexual dysfunction, stimulating sexual activity and enhancing sexual desire, interest or function. 18. A method for treating sexual dysfunction in a subject, comprising administering to the subject a fast-acting, orally administered pharmaceutical composition comprising a compound active in sexual dysfunction according to any one of claims 1-16. 19. The method of claim 18, comprising administering to the subject a fast acting oral pharmaceutical composition containing a compound active in sexual dysfunction according to any one of claims 1-16, in less than 1 hour, preferably less than 30 minutes before sexual activity.