WO2009068278A2 - A pharmaceutical composition - Google Patents
A pharmaceutical composition Download PDFInfo
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- WO2009068278A2 WO2009068278A2 PCT/EP2008/010051 EP2008010051W WO2009068278A2 WO 2009068278 A2 WO2009068278 A2 WO 2009068278A2 EP 2008010051 W EP2008010051 W EP 2008010051W WO 2009068278 A2 WO2009068278 A2 WO 2009068278A2
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- WIPO (PCT)
- Prior art keywords
- pharmaceutical composition
- carnitine
- acetyl
- hydrochloride
- male infertility
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
Definitions
- the present invention relates to medicine and, more particularly, to pharmaceutical compositions to prevent and treat sexual dysfunction in men.
- male infertility is the most serious problem.
- a prevailence of male infertility can be estimated concerning the following figures.
- Each 5 th - 6 th marriage worldwide is infertile. In Ukraine, taking into account a severe environmental situation and a number of other unfavorable social factors, infertility frequency is even higher.
- Male inability to produce children is the cause of infertile marriage in 50% of the cases. That is to say, each tenth marriage is shadowed by male infertility.
- mumps such current or previous diseases as mumps, viral hepatitis, rubella, urogenital tuberculosis, diabetes mellitus, sexually transmitted diseases (gonorrhea, syphilis, AIDS, clamidiosis, mycoplasmosis, and trichomoniasis), inflammation of a testis and its epididymis (orchiepididymitis), and non-descending testis (cryptorchism).
- One of the most common causes of male infertility is a varix dilatation of the spermatic cord (varicocele). Male infertility can be caused by damage to the spermatic cord during surgical operations, the obstruction of the excretory ducts of the seminal vesicles.
- Male infertility can be caused by radioactive irradiation, chemotherapy for the treatment of cancer, tobacco, drugs and alcohol, the use of anabolic steroids. There are also genetic and immunological causative factors of male infertility. Various methods and medicines are used for the treatment of male infertility.
- asthenozoospermia Another widespread problem is asthenozoospermia. This disorder is characterized by reduction in the number of mobile forms as well as in spermatozoon velocity in sperm. A number of slow-moving forms or sessile forms in asthenozoospermia exceeds 30%. The causes of asthenozoospermia are not finally determined but it is assumed that changes in the chemistry of sperm plasma, reduction in the ievei of carbohydrates or other energy substances thereof as well as reduction in or the disappearance of a negative electric charge on spermatozoon, the precipitation of various microorganisms, especially mycoplasmal infection, onto their surface play the principal role.
- Asthenozoospermia can also be caused by various disorders of spermatogenesis, which result not only in a smaller number of spermatozoon produced (oligozoospermia) but also in the production of their pathological, abnormal forms (teratozoospermia) incapable to move adequately. Asthenozoospermia can also lead to infertility. Therefore prevention and a timely treatment of asthenozoospermia, as well as the development of appropriate means of prevention and treatment, the increase of number of such means are important.
- a food additive disclosed in the Ukrainian Patent No. 26099 comprising L-carnitine as well as vitamins and minerals is known from the state of art.
- the energy stimulating sterile or non-sterile food additive comprises vitamins and minerals such as: sodium, potassium, magnesium, iron, zinc, copper, manganese, nickel, boron, cobalt, molybdenum, vanadium, fluorine, glycerol, glycine, EDTA, tartaric acid, ascorbic acid, succinic acid, lithium, citric acid and water, wherein the additive consisting of vitamins and/or minerals and/or amino acid and/or plants and extracts thereof and/or other not less important substances in %: 0.0057-0.342 of vitamin B1 (thiamine) and/or 0.005-0.4446 of vitamin B2 (riboflavin) and/or 0.0673-4.7882 of vitamin B3 (L-nicotinic acid) and/or 0.0067-1.026 of vitamin B5 (L-pantothenic acid) and/or
- the closest prior art of the claimed invention is a pharmaceutical composition that is disclosed in the United States Patent 5863940 and that comprises compounds of L- camitine fumarate and acetyl L-carnitine hydrochloride.
- a disadvantage of the disclosed composition is the lack of additional physiologically active substances in its composition this, in turn, fails to ensure a sufficient efficacy of the composition in the prevention and treatment of sexual dysfunctions in men.
- the object of the present invention is to provide a pharmaceutical composition which, due to the ingredients thereof, ensures an effective prevention and treatment of sexual dysfunctions in men as well as allows to provide an alternative medicament.
- the object set is achieved by a pharmaceutical composition
- a pharmaceutical composition comprising the compounds L-carnitine fumarate and L-carnitine acetyl hydrochloride, characterized in that the pharmaceutical composition comprises physiologically active substances in the following ingredient ratio (% w/w):
- the pharmaceutical composition further comprises Fructose in an amount of 10 to 34 % w/w.
- the pharmaceutical composition further comprises Sugar in an amount of 20 to 3o % w/w and Citric Acid in an amount of 0.5 to 1.5 % w/w.
- the pharmaceutical composition comprises the compounds L-carnitine fumarate and acetyl-L-carnitine hydrochloride, wherein it further comprises physiologically active substances in the following ingredient ratio (% w/w):
- L-carnitine is an amino acid which is also called a vitamin BT. L-carnitine promotes the use of fat as the main source of energy via an active transport of fatty acids into the mitochondria of a cell, where they break up with energy release. Cardiology, metabolism diseases, diabetology, nephrology, neurology, neuropsychiatry, immunology, oncology, andrology, neonatology, geriatrics - this is the incomplete list of the fields of medicine where carnitine is used. In addition, this compound is completely irreplaceable in sport, it is called a "training-like" factor due to its ability to optimize physical efforts. Participating in energy processes which occur in the "energy stations" of the cells, the mitochondrias, carnitine increases a body endurance and ability to restore.
- L-carnitine plays an important role in the cell metabolism of the myocardium and skeletal muscles, it regulates the metabolism of fatty acids thereby preventing lipids from being accumulated in the cells.
- L-carnitine promotes the enhancement of the detoxification function of the liver, protein and glycogen synthesis, a more active breakdown of lactic acid and pyruvic acid, which are "fatigue toxins”.
- L-carnitine ensures the maintenance of an optimum physiological condition and energy supply of the muscles during large exercise stresses and during athletic training.
- the use of L-camitine directly prior to an athletic training increases a muscle bulk due to the use of fat deposits.
- L-carnitine increases effectiveness and endurance during athletic training as well as performance efficiency during everyday physical activity including in people suffering from cardiac diseases.
- L-carnitine delays a brain ageing process, improves memory and attention concentration, facilitates a quick restoration after a stress, and reduces anxiety.
- L-carnitine stimulates food reflex, improves appetite in premature infants and hypotrophic newborns, eliminates a body weight deficit, influences favorably on the development of skeleton and muscles in children and teenagers. It should be also noted that sperm quality depends, in many respects, on the entry of L-carnitine and derivatives thereof into the body.
- L-carnitine is a component of both seminal fluid plasma and cells and plays an important role in spermatozoon maturation and potential motility.
- L-carnitine speeds up the utilization of energetically valuable lipids and thereby improves energy supply for the spermatozoon.
- Acetyl L-carnitine is also a circulating source of energy for all of the seminal fluid components responsible for spermatozoon motility. It has been found experimentally that the introduction of the compounds L-carnitine fumarate and L-carnitine acetyl hydrochloride to the pharmaceutical composition in a quantity of between 30% and 40% and between 10% and 55%, respectively, of the total weight thereof makes it possible to ensure spermatozoon maturation, division, and normal motility of male cells (spermatozoon) thereby improving sperm quality.
- sugar is added to the pharmaceutical composition in a quantity of between 20% and 30% of the total weight thereof.
- Sugar is added as an auxiliary substance because sugar is required for the cells of our body since energy is generated during its breakdown. Moreover, sugar is added as a sweetener.
- silicon is an element of life for any living organism and manifests itself as an important biotic (vitally important) factor in life sustenance of a human. Silicon is the second most abundant element. It forms long complex molecules and plays an important role in building the connective tissues of the body, bones, cartilages, and blood vessels. This element is required to produce collagen that is needed for the bone and connective tissues to maintain nail, skin, and hair health and to absorb calcium at early stages of osteogenesis. Silicon is extremely important for the biosynthesis of keratin, connective tissues, and cartilages.
- Silicon prevents the body from harmful effect of aluminum and is of a great importance in the prevention of Alzheimer's disease and osteoporosis. This element participates in the metabolism of calcium, chlorine, fluorine, sodium, sulfur, aluminum, zinc, molybdenum, manganese, cobalt, and other elements. Also, silicon has a rejuvenating, antimicrobial, and antiinflammatory effect. In the course of vital activity, the human body loses silicon because of parasitic invasions; a bad environment (poisoning with aluminum, lead, cadmium, and other heavy metals) oxidizing processes leading to the formation of free radicals, malnutrition stresses, etc.
- Citric acid is a crystalline white solid, melting point 153°C, freely soluble in water, soluble in ethanol, slightly soluble in diethyl ether. Citric acid is a weak, tribasic acid. Citric acid is a requisite component in the system of biochemical reactions of cell respiration in multiple organisms (the tricarboxylic acid (TCA) cycle, the glyoxylate cycle). Along with other components of the TCA cycle, citric acid is contained in small quantities in the mitochondria of all the cells. Another function of citric acid is to maintain the acid-base balance and ion composition in the body.
- Citric acid is an antibacterial and antiviral agent; improves food assimilation and digestion; is a strong complexing agent and forms hardly absorbable complexes with heavy metals including lead and cadmium. It is also proven that citric acid decreases the risk of the synthesis of carcinogenic nitrosamines in the body and, therefore, the risk of oncologic pathology development. It has been also proven that the addition of citric acid to the composition in a quantity of between 0.5% and 1.5% of the total mass thereof makes it possible to improve significantly energy metabolism.
- a lemon flavor is added to the composition of the invention to ensure a nice taste of the medicine.
- the addition of this flavor in a quantity of between 0.5% and 5% of the total mass of the composition is optimum to ensure a desired gustatory quality thereof.
- Fructose is one of the key metabolic products which provides the living cells with energy, is an initial product of the biosynthesis of many substances required for the body. Fructose has significant metabolic properties, a tonic affect, a good solubility, and a low viscosity. Following the uptake of fructose, a sugar level in the blood does not elevate rapidly with its further reduction, which is peculiar to glucose and sucrose. Fructose is detained by the liver to a greater extent and, therefore, comes to the blood in smaller quantities, enters sooner various metabolic processes. In the metabolic process, fructose turns into glucose but increase in the glucose level in the blood occurs smoothly and progressively not causing for example exacerbation of diabetes.
- fructose In addition, insulin is not required for fructose uptake and, therefore, no add itional stress for the pancreas is produced.
- Fructose is substantially incapable of causing caries.
- glycogen that serves as the source of energy for the body; glycogen is produced from fructose and provides the body with energy more uniformly as required.
- composition may further comprise pharmacologically acceptable excipients.
- excipients include any of the substances already mentioned, as well as any of those used conventionally, such as those described in Remington: The Science and Practice of Pharmacy (Gennaro and Gennaro, eds, 20th edition, Lippincott Williams & Wilkins, 2000); Theory and Practice of Industrial Pharmacy (Lachman et al., eds., 3rd edition, Lippincott Williams & Wilkins, 1986); Encyclopedia of Pharmaceutical Technology (Swarbrick and Boylan, eds., 2nd edition, Marcel Dekker, 2002). These can be referred to herein as "pharmaceutically acceptable excipients" to indicate they are combined with the active compounds and can be administered safely to a subject for therapeutic purposes.
- the invention further comprises the use of the pharmaceutical composition according to the invention for the treatment of male sexual dysfunction, in particular male infertility, whereby in another embodiment of the invention said male infertility is caused by asthenozoospermia.
- a further objective of the invention is to provide a method of treating and/or preventing male infertility, especially male infertility caused by asthenozoospermia, by orally administering a pharmaceutical composition according to the invention and as described above.
- the pharmaceutical composition can be administered at least once a day, preferably twice or thrice a day, especially preferred twice a day. Oral administration is preferred.
- composition in accordance with the present invention motility of more than 20% but less than 40%; sperm concentration of more than 10x10 6 /ml; remnant lipoprotein particles (RLP) of less than 20%; linear index of between 2 and 4
- the pharmaceutical composition in accordance with the present invention in the dosage form of powder was administered orally twice a day in the morning and in the evening during a meal for 3 - 6 months.
- the oral single dosage consisted of one 5 g-pouche of Androzol Powder (see table 1). Table 1
- composition in accordance with the present invention makes it possible to ensure an effective prevention and treatment of sexual dysfunction in men as well as allows to provide an alternative medicament.
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Abstract
The present invention relates to medicine and, more particularly, to pharmaceutical compositions to prevent and treat sexual dysfunction in men. The pharmaceutical composition comprising compounds L-carnitine fumarate and L-carnitine acetyl hydrochloride, characterized in that the pharmaceutical composition comprises physiologically active substances in the following ingredient ratio (% w/w): L-carnitine fumarate (30) to (40), Acetyl L-camitine hydrochloride (10) to (15), Silicon (5) to (10), and further pharmacologically acceptable excipients. Thus, the pharmaceutical composition in accordance with the present invention makes it possible to ensure an effective prevention and treatment of sexual dysfunction in men as well as allows to provide an alternative medicament.
Description
A pharmaceutical composition
The present invention relates to medicine and, more particularly, to pharmaceutical compositions to prevent and treat sexual dysfunction in men.
Currently, a large number of sexual dysfunctions in men are known among which male infertility is the most serious problem. A prevailence of male infertility can be estimated concerning the following figures. Each 5th - 6th marriage worldwide is infertile. In Ukraine, taking into account a severe environmental situation and a number of other unfavorable social factors, infertility frequency is even higher. Male inability to produce children is the cause of infertile marriage in 50% of the cases. That is to say, each tenth marriage is shadowed by male infertility. Unfortunately, multiple reasons can lead to male infertility. These include such current or previous diseases as mumps, viral hepatitis, rubella, urogenital tuberculosis, diabetes mellitus, sexually transmitted diseases (gonorrhea, syphilis, AIDS, clamidiosis, mycoplasmosis, and trichomoniasis), inflammation of a testis and its epididymis (orchiepididymitis), and non-descending testis (cryptorchism). One of the most common causes of male infertility is a varix dilatation of the spermatic cord (varicocele). Male infertility can be caused by damage to the spermatic cord during surgical operations, the obstruction of the excretory ducts of the seminal vesicles. Male infertility can be caused by radioactive irradiation, chemotherapy for the treatment of cancer, tobacco, drugs and alcohol, the use of anabolic steroids. There are also genetic and immunological causative factors of male infertility. Various methods and medicines are used for the treatment of male infertility.
Another widespread problem is asthenozoospermia. This disorder is characterized by reduction in the number of mobile forms as well as in spermatozoon velocity in sperm. A number of slow-moving forms or sessile forms in asthenozoospermia exceeds 30%. The causes of asthenozoospermia are not finally determined but it is assumed that changes in the chemistry of sperm plasma, reduction in the ievei of carbohydrates or other energy substances thereof as well as reduction in or the disappearance of a negative electric charge on spermatozoon, the precipitation of various microorganisms, especially mycoplasmal infection, onto their surface play the principal role. Asthenozoospermia can also be caused by various disorders of
spermatogenesis, which result not only in a smaller number of spermatozoon produced (oligozoospermia) but also in the production of their pathological, abnormal forms (teratozoospermia) incapable to move adequately. Asthenozoospermia can also lead to infertility. Therefore prevention and a timely treatment of asthenozoospermia, as well as the development of appropriate means of prevention and treatment, the increase of number of such means are important.
A food additive disclosed in the Ukrainian Patent No. 26099 comprising L-carnitine as well as vitamins and minerals is known from the state of art. The energy stimulating sterile or non-sterile food additive comprises vitamins and minerals such as: sodium, potassium, magnesium, iron, zinc, copper, manganese, nickel, boron, cobalt, molybdenum, vanadium, fluorine, glycerol, glycine, EDTA, tartaric acid, ascorbic acid, succinic acid, lithium, citric acid and water, wherein the additive consisting of vitamins and/or minerals and/or amino acid and/or plants and extracts thereof and/or other not less important substances in %: 0.0057-0.342 of vitamin B1 (thiamine) and/or 0.005-0.4446 of vitamin B2 (riboflavin) and/or 0.0673-4.7882 of vitamin B3 (L-nicotinic acid) and/or 0.0067-1.026 of vitamin B5 (L-pantothenic acid) and/or 0.004-0.6498 of vitamin B6 (pyridoxine) and/or 0.00002-0.0006 of vitamin B12 (cyanocobalamin) and/or 0.1682-11.68 of vitamin C (L-ascorbic acid or sodium ascorbate) and/or 0.0002-0.0136 of vitamin H (biotin) and/or 0.881-20.781 of L- gamma-aminobutyric acid (GABA) (aminolone) and/or 0.0006-0.0444 of vitamin Bc (L-folic acid) and/or 0.0033-0.342 of vitamin A (retinol) and/or 0.6059-6.6915 L- succinic acid and/or 2.7044-17.848 of L-asparaginic acid and/or 1.3459-71.085 of vitamin BT (L-carnitine) and/or 0.6729-5.2201 of L-alanine and/or 1.6824-6.1989 of L-glutamine and/or 2.6919-16.313 of L-leucine and/or 1.6824-14.355 of L-isoleucine and/or 1.6824-18.27 of L-valine and/or 1.3459-11.745 of L-glycine and/or 1.0094- 7.8302 of L-methionine and/or 0.8412-37.001 of L-phenylalanine and/or 0.8412- 6.5252 of L-tryptophan and/or 0.8412-29.325 of L-tyrosine and/or 0.8412-7.001 of L- cystine and/or 0.6729-10.108 of L-arginine and/or 2.3491-72.871 of taurine and/or 14.679-86.708 of glucose and/or 19.368-81.133 of fructose and/or 5.0474-45.31 of lactulose and/or 1.0094-4.8775 of Echinacea and/or 5.0474-39.02 of Spirulina and/or 6.7299-25.53 of creatine monohydrate and/or 0.0002-0.0139 of selenium and/or 1.6824-6.5252 of calcium and/or 0.3364-4.8775 of phosphorus and/or 0.3364- 3.902 of magnesium and/or 0.0001-0.0011 of chromium and/or 0.001-0.0373 of
octacosanol and/or 0.5047-16.021 glucuronolactone and/or 0.0673-5.3404 of sildenafil and/or 0.6729-12.622 of Tribulus and/or 0.1177-10.26 of yohimbine and/or 0.1468-11.002 of Saparalum or Leuzea and/or 0.2018-7.5704 of guarana and/or 0.1514-7.2671 of caffeine or mateine.
The disadvantages of this disclosed food additive are its low efficacy in the prevention and treatment of sexual dysfunctions in men since the main action thereof is directed at the improvement of human energy potential.
The closest prior art of the claimed invention is a pharmaceutical composition that is disclosed in the United States Patent 5863940 and that comprises compounds of L- camitine fumarate and acetyl L-carnitine hydrochloride.
A disadvantage of the disclosed composition is the lack of additional physiologically active substances in its composition this, in turn, fails to ensure a sufficient efficacy of the composition in the prevention and treatment of sexual dysfunctions in men.
The object of the present invention is to provide a pharmaceutical composition which, due to the ingredients thereof, ensures an effective prevention and treatment of sexual dysfunctions in men as well as allows to provide an alternative medicament.
The object set is achieved by a pharmaceutical composition comprising the compounds L-carnitine fumarate and L-carnitine acetyl hydrochloride, characterized in that the pharmaceutical composition comprises physiologically active substances in the following ingredient ratio (% w/w):
L-carnitine fumarate 30 to 40,
Acetyl L-carnitine hydrochloride 10 to 15,
Silicon 5 to 10, and further pharmacologically acceptable excipients.
In another embodiment of the present invention the pharmaceutical composition further comprises Fructose in an amount of 10 to 34 % w/w.
In a further embodiment of the invention the pharmaceutical composition further comprises Sugar in an amount of 20 to 3o % w/w and Citric Acid in an amount of 0.5 to 1.5 % w/w.
In another preferred embodiment the pharmaceutical composition comprises the compounds L-carnitine fumarate and acetyl-L-carnitine hydrochloride, wherein it further comprises physiologically active substances in the following ingredient ratio (% w/w):
L-carnitine fumarate 30 to 40
Acetyl L-carnitine hydrochloride 10 to 15
Sugar 20 to 30
Silicon 5 to 10
Citric acid 0.5 to 1.5
Lemon flavor 0.5 to 5
Fructose Q. S.
L-carnitine is an amino acid which is also called a vitamin BT. L-carnitine promotes the use of fat as the main source of energy via an active transport of fatty acids into the mitochondria of a cell, where they break up with energy release. Cardiology, metabolism diseases, diabetology, nephrology, neurology, neuropsychiatry, immunology, oncology, andrology, neonatology, geriatrics - this is the incomplete list of the fields of medicine where carnitine is used. In addition, this compound is completely irreplaceable in sport, it is called a "training-like" factor due to its ability to optimize physical efforts. Participating in energy processes which occur in the "energy stations" of the cells, the mitochondrias, carnitine increases a body endurance and ability to restore. L-carnitine plays an important role in the cell metabolism of the myocardium and skeletal muscles, it regulates the metabolism of fatty acids thereby preventing lipids from being accumulated in the cells. L-carnitine promotes the enhancement of the detoxification function of the liver, protein and glycogen synthesis, a more active breakdown of lactic acid and pyruvic acid, which are "fatigue toxins". L-carnitine ensures the maintenance of an optimum physiological condition and energy supply of the muscles during large exercise stresses and during
athletic training. The use of L-camitine directly prior to an athletic training increases a muscle bulk due to the use of fat deposits. L-carnitine increases effectiveness and endurance during athletic training as well as performance efficiency during everyday physical activity including in people suffering from cardiac diseases. L-carnitine delays a brain ageing process, improves memory and attention concentration, facilitates a quick restoration after a stress, and reduces anxiety. L-carnitine stimulates food reflex, improves appetite in premature infants and hypotrophic newborns, eliminates a body weight deficit, influences favorably on the development of skeleton and muscles in children and teenagers. It should be also noted that sperm quality depends, in many respects, on the entry of L-carnitine and derivatives thereof into the body. L-carnitine is a component of both seminal fluid plasma and cells and plays an important role in spermatozoon maturation and potential motility. Improving permeability of spermatozoon membrane for fatty acids, L-carnitine speeds up the utilization of energetically valuable lipids and thereby improves energy supply for the spermatozoon. Acetyl L-carnitine is also a circulating source of energy for all of the seminal fluid components responsible for spermatozoon motility. It has been found experimentally that the introduction of the compounds L-carnitine fumarate and L-carnitine acetyl hydrochloride to the pharmaceutical composition in a quantity of between 30% and 40% and between 10% and 55%, respectively, of the total weight thereof makes it possible to ensure spermatozoon maturation, division, and normal motility of male cells (spermatozoon) thereby improving sperm quality.
Preferably, sugar is added to the pharmaceutical composition in a quantity of between 20% and 30% of the total weight thereof. Sugar is added as an auxiliary substance because sugar is required for the cells of our body since energy is generated during its breakdown. Moreover, sugar is added as a sweetener.
The addition of silicon into the composition is expedient since the deficit thereof in the body results in that 70% of biologically active compounds and vitamins are not merely uptaken by the human body. Silicon is an element of life for any living organism and manifests itself as an important biotic (vitally important) factor in life sustenance of a human. Silicon is the second most abundant element. It forms long complex molecules and plays an important role in building the connective tissues of the body, bones, cartilages, and blood vessels. This element is required to produce
collagen that is needed for the bone and connective tissues to maintain nail, skin, and hair health and to absorb calcium at early stages of osteogenesis. Silicon is extremely important for the biosynthesis of keratin, connective tissues, and cartilages. It is also required to maintain artery wall elasticity and plays an important role in the prevention of cardiovascular diseases. Silicon prevents the body from harmful effect of aluminum and is of a great importance in the prevention of Alzheimer's disease and osteoporosis. This element participates in the metabolism of calcium, chlorine, fluorine, sodium, sulfur, aluminum, zinc, molybdenum, manganese, cobalt, and other elements. Also, silicon has a rejuvenating, antimicrobial, and antiinflammatory effect. In the course of vital activity, the human body loses silicon because of parasitic invasions; a bad environment (poisoning with aluminum, lead, cadmium, and other heavy metals) oxidizing processes leading to the formation of free radicals, malnutrition stresses, etc. In case of silicon deficit in the human body, the balance of energy supply and metabolism is being affected. The composition of liquid media changes, their properties as electrolytes fail to meet the physiological indices of a normal vital activity of human. As a result of silicon deficit in the human body, the following diseases develop: atherosclerosis, insult, infarct, cardiosclerosis, arrhythmia, disbolism, mental disorders, Alzheimer's disease, hypertension, osteoporosis, etc. It has been proven experimentally that the addition of silicon to the pharmaceutical composition in an amount of between 5% and 10% of the total weight thereof is sufficient to improve the total therapeutical effect from the administration of the composition.
Citric acid is a crystalline white solid, melting point 153°C, freely soluble in water, soluble in ethanol, slightly soluble in diethyl ether. Citric acid is a weak, tribasic acid. Citric acid is a requisite component in the system of biochemical reactions of cell respiration in multiple organisms (the tricarboxylic acid (TCA) cycle, the glyoxylate cycle). Along with other components of the TCA cycle, citric acid is contained in small quantities in the mitochondria of all the cells. Another function of citric acid is to maintain the acid-base balance and ion composition in the body. Citric acid is an antibacterial and antiviral agent; improves food assimilation and digestion; is a strong complexing agent and forms hardly absorbable complexes with heavy metals including lead and cadmium. It is also proven that citric acid decreases the risk of the synthesis of carcinogenic nitrosamines in the body and, therefore, the risk of
oncologic pathology development. It has been also proven that the addition of citric acid to the composition in a quantity of between 0.5% and 1.5% of the total mass thereof makes it possible to improve significantly energy metabolism.
Preferably, a lemon flavor is added to the composition of the invention to ensure a nice taste of the medicine. The addition of this flavor in a quantity of between 0.5% and 5% of the total mass of the composition is optimum to ensure a desired gustatory quality thereof.
Fructose is one of the key metabolic products which provides the living cells with energy, is an initial product of the biosynthesis of many substances required for the body. Fructose has significant metabolic properties, a tonic affect, a good solubility, and a low viscosity. Following the uptake of fructose, a sugar level in the blood does not elevate rapidly with its further reduction, which is peculiar to glucose and sucrose. Fructose is detained by the liver to a greater extent and, therefore, comes to the blood in smaller quantities, enters sooner various metabolic processes. In the metabolic process, fructose turns into glucose but increase in the glucose level in the blood occurs smoothly and progressively not causing for example exacerbation of diabetes. In addition, insulin is not required for fructose uptake and, therefore, no add itional stress for the pancreas is produced. Fructose is substantially incapable of causing caries. During a stress condition, it is glycogen that serves as the source of energy for the body; glycogen is produced from fructose and provides the body with energy more uniformly as required. These properties of fructose make it expedient for adding to the composition of the invention in order to intensify the therapeutic effects thereof.
The composition may further comprise pharmacologically acceptable excipients. Such excipients include any of the substances already mentioned, as well as any of those used conventionally, such as those described in Remington: The Science and Practice of Pharmacy (Gennaro and Gennaro, eds, 20th edition, Lippincott Williams & Wilkins, 2000); Theory and Practice of Industrial Pharmacy (Lachman et al., eds., 3rd edition, Lippincott Williams & Wilkins, 1986); Encyclopedia of Pharmaceutical Technology (Swarbrick and Boylan, eds., 2nd edition, Marcel Dekker, 2002). These
can be referred to herein as "pharmaceutically acceptable excipients" to indicate they are combined with the active compounds and can be administered safely to a subject for therapeutic purposes.
A proven fact is that therapy with L-carnitine in combination with fructose and silicon improves substantially spermatozoon capacitation and ability to undergo the acrosome reaction.
The invention further comprises the use of the pharmaceutical composition according to the invention for the treatment of male sexual dysfunction, in particular male infertility, whereby in another embodiment of the invention said male infertility is caused by asthenozoospermia.
A further objective of the invention is to provide a method of treating and/or preventing male infertility, especially male infertility caused by asthenozoospermia, by orally administering a pharmaceutical composition according to the invention and as described above.
In an embodiment of the inventive method the pharmaceutical composition can be administered at least once a day, preferably twice or thrice a day, especially preferred twice a day. Oral administration is preferred.
The efficacy of the composition is illustrated in the following example:
One hundred men diagnosed with idiopathic asthenozoospermia were selected to participate in a clinical study of the composition in accordance with the present invention: motility of more than 20% but less than 40%; sperm concentration of more than 10x106 /ml; remnant lipoprotein particles (RLP) of less than 20%; linear index of between 2 and 4 The pharmaceutical composition in accordance with the present invention in the dosage form of powder was administered orally twice a day in the morning and in the evening during a meal for 3 - 6 months. The oral single dosage consisted of one 5 g-pouche of Androzol Powder (see table 1).
Table 1
Sperm concentration increased by 7.7% from 49.9% up to 53.2 x 106 /ml. The total spermatozoon amount increased by 10.6% from 142 up to 157 x 106. The average motility increased up to 40.1%. Remnant lipoprotein particles changed by 66.7% (to 18%). Spermatozoon velocity increased and linear index elevated significantly as well. Abnormal sperm morphology percentage, in turn, decreased from 45.9 down to 42.9%.
Thus, the composition in accordance with the present invention makes it possible to ensure an effective prevention and treatment of sexual dysfunction in men as well as allows to provide an alternative medicament.
Claims
1. A pharmaceutical composition comprising compounds L-carnitine fumarate and L-carnitine acetyl hydrochloride, characterized in that the pharmaceutical composition comprises physiologically active substances in the following ingredient ratio (% w/w):
L-carnitine fumarate 30 to 40,
Acetyl L-carnitine hydrochloride 10 to 15,
Silicon 5 to 10, and further pharmacologically acceptable excipients.
2. A pharmaceutical composition according to claim 1 , characterized in that it further comprises Fructose in an amount of 10 to 34 % w/w.
3. A pharmaceutical composition according to claim 1 or 2, characterized in that it further comprises Sugar in an amount of 20 to 3o % w/w and Citric Acid in an amount of 0.5 to 1.5 % w/w.
4. A pharmaceutical composition according to any of the preceeding claims, characterized in that the pharmaceutical composition comprises the following ingredient ratio (% w/w):
L-carnitine fumarate 30 to 40
Acetyl L-carnitine hydrochloride 10 to 15
Sugar 20 to 30
Silicon 5 to 10
Citric acid 0.5 to 1.5
Lemon flavor 0.5 to 5
Fructose Q. S.
5. Use of the pharmaceutical composition according to any of claims 1 to 4 for the treatment of male sexual dysfunction, in particular male infertility.
6. Use according to claim 5 whereby the male infertility is caused by asthenozoospermia.
7. Method of treating and/or preventing male infertility, especially male infertility caused by asthenozoospermia, by orally administering a pharmaceutical composition according to any of claims 1 to 4.
8. Method according to claim 7 whereby the oral administration is performed twice a day.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| UA200713326 | 2007-11-30 | ||
| UA2007013326 | 2007-11-30 | ||
| EA200800221 | 2008-01-31 | ||
| EA200800221A EA200800221A1 (en) | 2008-01-31 | 2008-01-31 | PHARMACEUTICAL COMPOSITION |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2009068278A2 true WO2009068278A2 (en) | 2009-06-04 |
| WO2009068278A3 WO2009068278A3 (en) | 2009-12-23 |
Family
ID=40626947
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP2008/010051 Ceased WO2009068278A2 (en) | 2007-11-30 | 2008-11-27 | A pharmaceutical composition |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2009068278A2 (en) |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6090848A (en) * | 1997-12-01 | 2000-07-18 | Sigma-Tau Healthscience S.P.A. | Compositions and methods for increasing the concentration and/or motility of spermatozoa in humans |
| US20060211721A1 (en) * | 2005-03-21 | 2006-09-21 | Roberts Alan R | Nutraceutical formulation of a cognitive enhancement system |
| US20070072910A1 (en) * | 2005-09-29 | 2007-03-29 | Smith Michael L | Compositions and methods for lowering plasma concentrations of low density lipoproteins in humans |
-
2008
- 2008-11-27 WO PCT/EP2008/010051 patent/WO2009068278A2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| WO2009068278A3 (en) | 2009-12-23 |
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