US20120095100A1 - Use of a combination of d-aspartic and l-aspartic acids or salts thereof for the treatment of male infertility - Google Patents
Use of a combination of d-aspartic and l-aspartic acids or salts thereof for the treatment of male infertility Download PDFInfo
- Publication number
- US20120095100A1 US20120095100A1 US13/320,780 US201013320780A US2012095100A1 US 20120095100 A1 US20120095100 A1 US 20120095100A1 US 201013320780 A US201013320780 A US 201013320780A US 2012095100 A1 US2012095100 A1 US 2012095100A1
- Authority
- US
- United States
- Prior art keywords
- aspartic acid
- aspartic
- aspartate
- vitamin
- treatment
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
Definitions
- the present invention concerns the use of a combination of D-aspartic and L-aspartic acids or salts thereof for the treatment of male infertility.
- the invention concerns the use of a mixture consisting of a mixture of D-aspartic and L-aspartic acids or salts thereof, preferably at least at ratio 1:1 in order to stimulate the man procreative activity by means of an increment of spermatozoon number and motility.
- the male infertility can be caused by disorders relating to spermatozoon production, emission or functionality and represents approximately 35% of couple infertility causes. It can be caused by possible past or presently occurring genitourinary infections; diseases like the varicella, measles or parotitis, viral disease that in men can result in orchitis (testicle infection); sexual transmission diseases; past surgeries or genital level traumas. Moreover, the life style, as the use of alcohol, smoke, drugs and hazardous works and environmental factors can play an important role. Varicocele can result in active spermatozoon generation deficit. Also FSH (follitropin), LH (luteotropin), PRL (prolactin) and T (testosterone) altered levels can affect the process of spermatozoon production.
- FSH follitropin
- LH luteotropin
- PRL prolactin
- T testosterone
- Menotropin active principle in menogon vials, comprising a preparation of gonadotropines (FSH and LH, in equal amount) extracted from post-menopause woman urine, therefore named menopause human hormone (HMG), is used.
- HMG acts directly on ovaries and testicles, by stimulating the ovulation process, spermatogenesis and steroidogenesis.
- FSH is essentially involved in stimulation of Sertoli cell maturation and affects moreover the maturation of seminipher tubules and the development of the spermatozoa.
- HCG is not effective if orally administered and must be administered intramuscularly.
- anti-HCG antibody formation can be taken place as a result of a cyclical repeated administration of the product, thus resulting in an ineffective therapy.
- a further disadvantage of this therapy is high cost, since most used therapy scheme involves the intramuscular administration three times a week over a three month cycle and low patient compliance due to the repeated intramuscular weekly administrations.
- GnRH gonadotropine
- This therapy involves a pulsed administration using portable pump (intravenously or subcutaneously) at 90-120 minute intervals. Although such a treatment within three months restores the concentrations of testosterone and gonadotropines and stimulates the spermatogenesis, on the other hand it implies that the patient must carries a portable pump equipped with urinary catheter and this can be uncomfortable for these patients.
- antiestrogens As to oral therapies, the same can comprise antiestrogens. These compounds (clomifen citrate and tamoxifene) have been widely used for the treatment of male infertility, in the absence of endocrine pathologies. Antiestrogens maintain ability to bind competitively estrogen receptors, both at hypothalamic and peripheral level, thus inducing an increase of gonadotropine plasma levels and secondarily intratesticular testosterone. The pharmacological effect on spermatogenesis would have to be exerted through the concentration increase of these hormones acting directly on the spermatogenesis. In particular clomifen citrate at low dosages (25-50 mg) administered for a 3-5 month is suitable to improve the semen characteristics, while higher concentrations (200-400 mg) induce a spermatogenesis suppression and reduction of sperm concentration.
- aromatase inhibitors can be used.
- testolactone 1 g/day
- testolactone 1 g/day
- testolactone doses 2 g/day
- Another compound displaying selective inhibitory activity on aromatase is anastrozole, that at 1 mg daily dose appears to be similar to testolactone for effects on spermatogenesis.
- L-arginine or other L-amino acid combinations and/or vitamin supplements as coadjuvants in oligoastenospermia and hyposomia, by oral administration 2-3 times daily for three months.
- D-aspartic acid is a natural amino acid detected firstly in 1977 by Antimo D'Aniello within octopus (marine mollusc scientifically named Octopus vulgaris ) brain as published in collaboration with Antonio Giuditta in J. of Neurochemistry (Ref. 1-2). Successive researches carried out by the same author in collaboration with other Italian and not Italinan researchers have demonstrated that the D-aspartic acid occurs not only in the nervous, but also in the endocrine system of many marine as mollusc, crustacean, opisthobranc and fish (Ref. 3-5) and terrestrial animals, as frog (Ref. 6-7), lucertola (Ref. 8), chicken (Ref.
- D-aspartic acid is present in a greater amount compared to more advanced ones.
- this amino acid in mammals, including humans is found at elevated concentrations in brain where it plays a role in the development of nervous system.
- D-aspartic acid is present ad elevated concentrations in endocrine system and particularly in pituitary gland and testicle where it plays a role in the endocrine system.
- D-aspartic acid in rat have evidenced that, if this compound is orally administered, it is suitable to induce a temporary increase in blood of some hormones as: luteinizing hormone (LH) (Ref: 17-18), growth hormone (Ref: 18), prolactin (PRL) (Ref: 19) and testosterone (Ref: 17-18). Finally recently it has been also demonstrated that D-aspartic acid is involved in human male infertility (Ref. 20).
- D-aspartic acid is present at concentration of 80 ⁇ 24 nmol/ml in seminal liquid and 130 ⁇ 30 fmol/spermatozoon.
- the content of the D-aspartic acid is meaningfully reduced both in seminal liquid and spermatozoa.
- D-aspartic acid is approximately 3 fold lower and in azoospermia suffering subjects is 6 fold lower.
- Table 2 shows the content of D-aspartic acid in human seminal liquid and spermatozoa.
- the values indicate the average and standard deviation obtained from 10 seminal liquid samples from normal donors, 10 seminal liquid samples from oligoastenoteratospermic donors (seminal liquid containing a spermatozoon number lower than 20 millions/ml of semen) and 10 seminal liquid samples from not obstructive azoospermic donors (donors with a spermatozoon number lower than 1 million/ml of semen).
- D-aspartic acid value was obtained using a specific HPLC chromatographic method in combination with D-aspartate oxidase.
- the difference of D-aspartic acid among normospermic and oligoastenoteratospermic donors was significant for P ⁇ 0.01 and the difference among oligoastenoteratospermic and azoospermic donors also was significant for P ⁇ 0.01.
- the authors of the present invention have now found that the combination of D-aspartic and L-aspartic acids results in a remarkable effectiveness increase compared to the administration of equal amount of alone D-aspartic acid.
- the authors have carried out studies both on animal and man demonstrating a greater increment of spermatozoon number and motility for the subjects treated with the inventive combination compared to those treated with alone D-aspartic acid. In particular in the man an increase of LH and testosterone hormone levels is observed also.
- composition comprising or consisting of the combination of D-aspartic and L-aspartic acids or one or more corresponding salts thereof of alkaline or alkaline earth metals, or comprising or consisting of alone L-aspartic acid, said active principles being possibly in combination with one or more pharmaceutically acceptable excipient and/or coadjuvant, for use in the treatment of male infertility.
- the concentration of D-aspartic acid or salts thereof can vary from 50% to 99.5% while, the concentration of L-aspartic acid or salts thereof can vary from 0.05% to 50%, said percentages being based on total weight of D-aspartic and L-aspartic acids or salts thereof.
- the concentration of D-aspartic acid or salts thereof can vary from 50% to 80% and the concentration of L-aspartic acid or salts thereof can vary from 20% to 50%, said percentages being based on total weight of D-aspartic and L-aspartic acids or salts thereof.
- the concentration of D-aspartic acid or salts thereof is 80% and the concentration of L-aspartic acid or salts thereof is 20%, said percentages being based on total weight of D-aspartic and L-aspartic acids or salts thereof.
- the concentration of D-aspartic acid or salts thereof or of L-aspartic acid or salts thereof is 50%, said percentages being based on total weight of D-aspartic and L-aspartic or salts thereof.
- the concentration of D-aspartic acid or salts thereof is 99.5% and the concentration of L-aspartic acid or salts thereof is 0.05%, said percentages being based on total weight of D-aspartic and L-aspartic acids or salts thereof.
- the present invention refers to not obstructive male infertility characterized by oligo and/or astenozoospermia with or without hypogonadotropic hypogonadism.
- the salt of D-aspartic acid or L-aspartic is a sodium salt or a mixture of sodium and potassium or magnesium or zinc salts.
- composition according to the invention can comprise one or more coadjuvants selected from the group consisting of amino acids, vitamins, minerals, reproductive function stimulating hormones, kallikrein, antibiotics, anti-inflammatory agents, antiandrogens, androgens, pentoxifilline, gonadotropine, gonadotropine releasing hormone (GnRH), adrenergic stimulators, dietetic supplements, anti-oxidants (alpha-lipoic acid, Q 10 coenzyme, glutathione and other not here mentioned anti-oxidants), ketoacids as for example oxaloacetic and alpha-ketoglutaric acids.
- coadjuvants selected from the group consisting of amino acids, vitamins, minerals, reproductive function stimulating hormones, kallikrein, antibiotics, anti-inflammatory agents, antiandrogens, androgens, pentoxifilline, gonadotropine, gonadotropine releasing hormone (GnRH), adrenergic stimulators, dietetic supplements, anti-oxidants (alpha
- amino acids can be chosen from the group consisting of alanine, arginine, carnitine, cysteine, glutamine, glicine, leucine, lisine, isoleucine, methionine, ornithine, phenyl alanine, threonine, tryptophan, valine, serine.
- the vitamins can be chosen from the group consisting of vitamin A, C, D3, E, K, B1, B2, B6, B12, PP, biotin (H), folic acid, lipoic acid.
- the minerals are chosen from the group consisting of magnesium, potassium, zinc, manganese, molybdenum, chromium, selenium, calcium pantothenate, iron, copper, iodine, phosphorus, fluorine, calcium.
- the vitamins can be used at variable concentration as below: vitamin A from 0.0048% to 0.024%, vitamin C from 0.36% to 3.6%, vitamin D3 from 0.00003% to 0.00015%, vitamin E from 0.06% to 0.6%, vitamin K from 0.00042% to 0.0021%, vitamin B1 from 0,0084 to 0.042%, vitamin B2 from 0.0096% to 0.048%, vitamin B6 from 0.012% to 0.06%, vitamin B12 from 6,10 ⁇ 6 % to 3,10 ⁇ 5 %, vitamin PP from 0.108% to 0.54%, biotin from 0.0009% to 4.4,10 ⁇ 5 %, folic acid from 0.0012% to 0.006%, said percentages being % weight based on total composition weight.
- the concentrations of minerals can vary according to the following percentages: magnesium from 3.2% to 9%, potassium from 0.4% to 4%, zinc from 0.09% to 0.45%, manganese from 0.02% to 0.07%, molybdenum, chromium or selenium from 0.0003% to 0.002%, calcium pantothenate from 0.04% to 0.15%, iron from 0.084% to 0.021%, copper from 0.02% to 0.1%, iodine from 0.0009% to 0.0045%, phosphorus from 2.5% to 20%, fluorine from 0.005% to 0.02%, calcium from 3.24% to 16.2%, said percentages being % weight based on total composition weight.
- concentrations of amino acids in addition to D-aspartic and L-aspartic acids can vary from 0.6% to 10% by weight based on total composition weight.
- the composition can comprise, in addition to D- and L-aspartate, folic acid, vitamin B6, vitamin B12 and potassium sorbate and sodium benzoate preservatives.
- concentrations can vary as below: folic acid from 0,002% to 0,006%, vitamin B6 from 0,02% to 0.06%, vitamin B12 from 1.10 5 % to 3.10 ⁇ 5 %, potassium sorbate from 0.002 to 0.008%, sodium benzoate from 0.002 to 0.008%.
- composition according to the present invention can be administered as daily dose variable from 0.001 g/day to 10 g/day.
- the concentrations of vitamins and minerals therefore can vary from 30% to 150% of RDA (suggested daily dose).
- RDA suggested daily dose
- Table 3 various compounds and minimum and maximum doses thereof that can be contained in a drug unit dose of the composition according to the invention.
- the percentages are % weight based on the composition weight of a 3.12 g commercial dose of active principle.
- the composition is in form of salt solution containing 9-11 ml/bottle, or in granule form with 3 g dose of active principle of D/L-aspartate and other ingredients amounting to a 3.5-6.0 g total dry weight.
- FIG. 1 shows LH (luteinizing hormone) increment in human plasma after treatment with the composition according to the invention.
- Reported values represent the average values and standard deviation (S.D.) obtained from ten 25-40 year old people at time zero and 10, 20 and 30 day after treatment (see bibliography below).
- FIG. 2 shows testosterone increment in human plasma after the treatment with the composition according to the invention.
- Reported values represent the average values and standard deviation (S.D.) obtained from ten 25-40 year old people at time zero and 10, 20 and 30 day after treatment (see bibliography below).
- FIG. 3 shows the increment of spermatozoon number in human seminal liquid after treatment with the composition according to the invention (see bibliography below).
- FIG. 4 shows the increment of spermatozoon number in human seminal liquid after treatment with the composition according to the invention.
- Reported values represent the average values and standard deviation (S.D.) obtained from ten 25-40 year old people at time zero and 30, 60 and 90 day after treatment (see bibliography below).
- FIG. 5 shows HPLC analysis of known sample consisting of a standard mixture of D-aspartic together with L-amino acid mixture (see bibliography below).
- D-aspartic and L-aspartic acids are commercially available in water insoluble powder form. It is necessary therefore the amino acid to be solubilised by sodium, potassium or magnesium salt formation.
- sodium D-aspartate at 2 M concentration corresponding to 266 g of D-aspartic acid/l in turn corresponding to 312 g of sodium D-aspartate/l, is reported.
- 10 ml of the solution contain 2,49 g of sodium D-aspartate and 0,63 g of sodium L-aspartate (corresponding to 2.128 g of D-aspartic acid and 0,530 g of L-aspartic acid respectively).
- said preparation can be obtained according to the following procedure which is also more practical: Add to 750 ml of 2,66 M NaOH (2.66 M NaOH solution corresponds to 106.6 g of NaOH/l) under stirring 212,8 g of D-aspartic acid and 53,2 g of L-aspartic acid. Continue the stirring until all amino acid is dissolved. After complete solubilisation, check the pH value which must be between 6.0 and 7.0. If pH is higher than 7.0, then add a few ml of 2M HCl until pH is between 6.0 and 7.0. If on the contrary pH is lower than 6.0, then add some ml of 2M NaOH till pH is between 6.0 and 7.0.
- 10 ml of the solution contain 2.49 g of sodium D-aspartate and 0.63 g of sodium L-aspartate (corresponding to 2.128 g of D-aspartic acid and 0.530 g of L-aspartic acid respectively).
- the sodium D-aspartate solution is prepared as below: Add to 750 ml of NaOH 2.66 M (NaOH 2.66 M corresponds to 106.6 g of NaOH/litre) add under agitation 266 g D-aspartic acid. Stir continuously until all the D-aspartic is dissolved. After solubilisation the pH of the solution must be between 6.0-7.0. If it is higher than 7.0, then adjust pH to 6.0-7.0 with few ml of 2 M HCl. If on the contrary the pH is lower than 6.0-7.0, then add more NaOH until the pH is 6.0-7.0. Then add 0,9 g of potassium sorbate and 0,9 g of sodium benzoate.
- D-aspartate and L-aspartate as sodium or potassium or magnesium salts are commercially available.
- DL-aspartate sodium salt consisting of DL-aspartate racemic mixture, i.e. 50% sodium D-aspartate and 50% sodium L-aspartate, is also commercially available. Therefore, it is also possible monodose sachets containing determined dose of sodium D-aspartate (3.12 g), to be prepared. To this dose 2 mg of B6 vitamin, 0.3 mg of folic acid and 1.5 ⁇ cg of B12 vitamin and possibly determined amounts of orange or other aroma, saccharose or other excipients in order to have a palatable ingestion, are then added. In this preparation nor sodium benzoate neither potassium sorbate are added being drug in powder form and thus not microorganism contaminable. Then the sachet is dissolved in drinkable water and ingested.
- the study has been carried out on two groups of rabbits (10 rabbits for each group) in order to test the effect of sodium D-aspartate and of the sodium D-aspartate in combination with a determined amount of sodium L-aspartate on the quality of seminal liquid, i.e. on number of spermatozoa/ml and on the progressive quick motility thereof.
- the experiment involved the ingestion by a group of 10 male adult rabbits, 6 month old, of an amount of sodium D-aspartate corresponding to 0.250 g daily (1.6 ⁇ moli/rabbit; 0.26 ⁇ moli/kg of body weight) over 20 days. Practically, sodium D-aspartate was mixed with food in such amount that the food daily ingested by the rabbit contained 0.250 g of sodium D-aspartate.
- a mixture consisting of 0.2 g of sodium D-aspartate and 0,05 g of sodium L-aspartate (80% D-Asp: 20% L-Asp) was administered.
- the number of the spermatozoa and progressive quick motility are determined according to (World Health Organization) WHO guidelines using a Makler Chamber for the count (Sefi Medtstl Instrument, Haifa, Israel) and in the same place the progressive quick motility has been determined.
- the rabbit semen was 1:10 diluted in an iso-osmotic solution due to excessive concentration.
- progressive quick motility of the spermatozoa was statistically improved.
- progressive quick spermatozoa found in seminal liquid of rabbit first group amount to 40% while after the treatment with D-aspartate the average value thereof was 55%, that is increase by 37%.
- the average value of quick spermatozoa number varied from 39% to 58%, that is increase by 48% (Table 5; part B; 2° group of rabbits).
- the results are referred to average values obtained on one group of 10 adult rabbits (6 month old) before the treatment and 20 days after the ingestion of 0.25 g sodium D-aspartate (1,60 ⁇ mole/rabbit; 0.26 ⁇ mol/kg of body weight) and on a group of other same age 10 rabbits before the treatment and 20 days after the ingestion of a mixture consisting of 0.2 g of sodium D-aspartate and 0,05 g of sodium L-aspartate daily and for 30 days (80% of Na-D-aspartate and 20% of Na-L-aspartate).
- part B of the table the values with asterisk are referred to percentage values of number of quick progressive, slow, immobile spermatozoa on 100 base.
- the values in parenthesis are referred to the percentage of the increases of quick progressive spermatozoa with respect to values before respective drug treatment
- D-Asp 50%: L-Asp 50% sodium L-aspartate
- the results are referred to average values from a number of 10 25-40 year old subjects before treatment and after daily ingestion for 30 days of 3.0 g of sodium D-aspartate/day (1° group of 10 people) and a group of 10 same age subjects before treatment and after daily ingestion for 30 days of 2.49 g of sodium D-aspartate and 0,63 g of sodium L-aspartate (80% sodium D-aspartate and 20% sodium L-aspartate).
- the values in parenthesis in part A of the table are referred to % increment of LH and testosterone before and after respective treatment.
- the values with asterisk of part B of the table are referred to % value of the number of quick progressive, slow, immobile spermatozoa on base 100.
- FIGS. 1 and 2 the diagram of increased values for LH and testosterone in human blood before and after treatment with the composition according to the invention (80% sodium D-aspartate and 20% sodium L-aspartate) is reported.
- FIGS. 3 and 4 the diagram of increased values of the number of spermatozoa and their progressive quick motility before and after treatment with the composition according to the invention is reported.
- FIG. 5 shows an example of HPLC analysis of a standard sample consisting of a standard mixture of D-aspartic together with L-amino acid mixture.
- Left panel shows HPLC analysis of a standard mixture consisting of D-Asp and other L-amino acids.
- the diagram represents an example of a chromatogram obtained using 10 picomol of D-Asp and 20 picomol of following other amino acids: Glu, Asn, Gln, Ser, Thr, His, Gly, Arg, Wing, Taurine, GABA, Tyr, Val, Met, Leu, Ile, Phe and Lys.
- e D-Asp is eluted at 5.2 min followed by L-Asp and other L-amino acids.
- the data is expressed as average ⁇ SD using Student T test. P ⁇ 0.05 has been considered statistically significant.
- the study has been carried out on two groups of rabbits.
- a first group consisting of 10 rabbits having 6 month old (approximately 5 kg of body weight) fed for 20 days with food mixture containing the mixture of 80% D-aspartic and 20% L-aspartic acids (see above: “Example of preparation of feed containing a combination of 80% D-aspartic acid and 20% L-aspartic acid”).
- a same age second group of 10 rabbits representing a control group (or placebo) was fed eat for 20 days with same type food as above prepared, but without the addition of D-aspartic and L-aspartic acids mixture.
- the experiments have been carried out in a rabbit breeding farm (“Potenza Breeders' Association”, Potenza, Italy).
- the number of the spermatozoa and progressive quick motility are determined according to (World Health Organization) WHO guidelines using a Makler Chamber for the count (Sefi Medtstl Instrument, Haifa, Israel) and in the same place the progressive quick motility has been determined.
- the rabbit semen was 1:10 diluted in an iso-osmotic solution due to excessive concentration and then analysed (note: each rabbit weighed approximately 5 kg and consumed approximately 200 g of food daily. Since 1 g of feed contained 4.56 mg of D-aspartic acid and 1.14 mg of L-aspartic acid it resulted that in a day the rabbit assumed a total of 912 mg of D-aspartic acid and 228 mg of L-aspartic acid)
- Values reported in part A of the table refer to average number of spermatozoa/ml of seminal liquid before the drug treatment and after 20 days of treatment.
- Values reported in part B of the table refer to spermatozoon motility in terms of quick, slow and immobile spermatozoa on base 100.
- Values reported in part A of the table refer to average number of spermatozoa/ml of seminal liquid before the drug treatment and after 20 days of treatment.
- Values reported in part B of the table refer to spermatozoon motility in terms of quick, slow and immobile spermatozoa on base 100.
- Values reported in part A of the table refer to average number of spermatozoa/ml of seminal liquid before the drug treatment and after 20 days of treatment.
- Values reported in part B of the table refer to spermatozoon motility in terms of quick, slow and immobile spermatozoa on base 100.
- D-aspartic acid in animal tissues including man is found in several tissues at high concentration in endocrine glands: hypophysis and testicles, is synthesised in the organism through enzyme named D-aspartate racemase having the property to synthesize D-aspartic acid by conversion of L-aspartic acid (References 21-26 and table 10).
- D-Aspartate racemase (L-Asp--->D-Asp) Tissues (Enzyme unit/g tissue) Testicle 40 U/g tissue Pituitary gland 30 U/g tissue Brain 22 U/g tissue Liver 15 U/g tissue Kidney 8 U/g tissue Serum 0.2 U/g tissue The enzymatic activity is determined by incubation of 1 ml of reaction mixture consisting of 10 MM L-Asp 10 in borate buffer 0.M pH 8,0 at 37° C. for 60 min, with 1 ml of tissue homogenate 1:10 in borate buffer, 0.1 M pH 8.0.
- 1 enzyme unit is defined as the enzyme amount suitable to convert 1 ⁇ mol of L-Asp to D-Asp under the conditions of enzymatic test.
- Values reported in part B of the table refer to spermatozoon motility in terms of quick, slow and immobile spermatozoa on base 100.
- the experiment has been carried out on ten 25-40 year old voluntary males selected for quality of seminal liquid being normal or almost normal.
- the mixture consisted of 80% D-aspartic acid and 20% L-aspartic acid.
- the D-aspartic and L-aspartic acid mixture preferably was dispersed in a half filled glass containing water or fresh or stored fruit juice (orange, apple, pear, etc.), then stirred and ingested.
- the seminal liquid has been collected by masturbation after 3-5 abstinence days.
- the number of the spermatozoa and progressive quick motility have been determined according to (World Health Organization) WHO guidelines using a Makler Chamber for the count (Sefi Medtstl Instrument, Haifa, Israel) and in the same place the progressive quick motility has been determined.
- Spermatozoon motility means progressive speed as determined on the base of ocular field travelling time and is expressed as percentage of progressive quick spermatozoa of 100 observed spermatozoa. The average increments for hormones, number and motility of the spermatozoa are all significant for T Student; P ⁇ 0.01.
- Spermatozoon motility means progressive speed as determined on the base of ocular field travelling time and is expressed as percentage of progressive quick spermatozoa of 100 observed spermatozoa. The average increments for hormones, number and motility of the spermatozoa are all significant for T Student; P ⁇ 0.01. Preparation of Supplement and Combination with Excipients
- the addition of suitable dose of the following supplements could be useful for the drug enhancement in terms of efficiency: zinc oxide in amount of 5-10 mg/drug dose (zinc occurs in seminal liquid and it is thought that positively affects the testosterone regulation within the prostate).
- Q-10 coenzyme in amount of 10-20 mg/drug dose Q10 coenzyme is an important anti-oxidant agent and protect the cells against free radicals
- other excipients useful in order to improve drug acceptability as for example Vitamins, folic acid etc in amounts as accepted for food use.
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ITRM2009A000253A IT1395957B1 (it) | 2009-05-19 | 2009-05-19 | Uso di una combinazione di d-aspartato e l-aspartato per il trattamento della infertilita' maschile. |
ITRM2009A000253 | 2009-05-19 | ||
PCT/IT2010/000222 WO2010134117A1 (en) | 2009-05-19 | 2010-05-19 | Use of a combination of d-aspartic and l-aspartic acids or salts thereof for the treatment of male infertility |
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US14/288,439 Active US10342826B2 (en) | 2009-05-19 | 2014-05-28 | Use of a combination of D-aspartic and L-aspartic acids or salts thereof for the treatment of male infertility |
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US14/288,439 Active US10342826B2 (en) | 2009-05-19 | 2014-05-28 | Use of a combination of D-aspartic and L-aspartic acids or salts thereof for the treatment of male infertility |
US16/504,372 Active US11524031B2 (en) | 2009-05-19 | 2019-07-08 | Use of a combination of D-aspartic and L-aspartic acids or salts thereof for the treatment of male infertility |
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US (3) | US20120095100A1 (ja) |
EP (1) | EP2432463B1 (ja) |
JP (1) | JP5833545B2 (ja) |
KR (3) | KR20120038408A (ja) |
CN (1) | CN102438611A (ja) |
AU (1) | AU2010250747B2 (ja) |
BR (1) | BRPI1011103B8 (ja) |
CA (1) | CA2759674C (ja) |
EA (1) | EA021832B1 (ja) |
ES (1) | ES2555387T3 (ja) |
IL (1) | IL216112A (ja) |
IT (2) | IT1395957B1 (ja) |
MX (1) | MX2011012323A (ja) |
SG (1) | SG175304A1 (ja) |
WO (1) | WO2010134117A1 (ja) |
ZA (1) | ZA201107764B (ja) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IT1395957B1 (it) | 2009-05-19 | 2012-11-02 | Pharmaguida S R L | Uso di una combinazione di d-aspartato e l-aspartato per il trattamento della infertilita' maschile. |
CN102603551A (zh) * | 2011-12-20 | 2012-07-25 | 安徽华恒生物工程有限公司 | 一种d-天冬氨酸二价盐及其制备方法 |
CN102631663B (zh) * | 2012-05-02 | 2014-08-20 | 张风帆 | 一种治疗男性不育、阳痿早泄的制剂及其应用 |
MX356383B (es) * | 2013-11-12 | 2018-05-24 | Cadila Healthcare Ltd | Formulación líquida de gonadotropina estabilizada con polietilenglicol. |
CN106563124A (zh) * | 2016-10-19 | 2017-04-19 | 广西大学 | 硫辛酸作为疫苗佐剂的应用 |
FR3070263B1 (fr) * | 2017-08-28 | 2020-07-24 | Serelys Pharma S A M | Composition pour son utilisation dans le traitement et/ou la prevention de l’infertilite |
Citations (2)
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US5389359A (en) * | 1993-06-28 | 1995-02-14 | Miwon Co., Ltd. | Pharmaceutical preparation containing L-aspartate or L-asparagine for preventing ethanol toxicity, and process for preparation thereof |
US5397786A (en) * | 1993-01-08 | 1995-03-14 | Simone; Charles B. | Rehydration drink |
Family Cites Families (9)
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GB8607570D0 (en) * | 1986-03-26 | 1986-04-30 | Euro Celtique Sa | Vaginal pharmaceutical preparation |
US5863940A (en) * | 1997-12-01 | 1999-01-26 | Sigma-Tau Healthscience S.P.A. | Medicament and therapeutical method for treating idiopathic asthenozoospermia |
US6632449B2 (en) * | 2001-11-20 | 2003-10-14 | The Procter & Gamble Co. | Compositions and kits comprising a defined boron compound and methods of their preparation |
WO2005120488A1 (en) * | 2004-06-10 | 2005-12-22 | Sara Sarig | Aspartic acid for the regeneration of bone matter |
PL219509B1 (pl) * | 2005-02-04 | 2015-05-29 | Repros Therapeutics Inc | Zastosowanie kompozycji zawierającej trans-klomifen |
US20060210692A1 (en) * | 2005-03-18 | 2006-09-21 | Mower Thomas E | Baby food composition |
ITRM20050468A1 (it) * | 2005-09-14 | 2007-03-15 | Marzocchella Teresa | Uso dell'acido d-aspartico o dei suoi sali per il trattamento della infertilita' maschile. |
US8202908B1 (en) * | 2008-03-28 | 2012-06-19 | Thermolife International, Llc | D-aspartic acid supplement |
IT1395957B1 (it) | 2009-05-19 | 2012-11-02 | Pharmaguida S R L | Uso di una combinazione di d-aspartato e l-aspartato per il trattamento della infertilita' maschile. |
-
2009
- 2009-05-19 IT ITRM2009A000253A patent/IT1395957B1/it active
-
2010
- 2010-05-19 US US13/320,780 patent/US20120095100A1/en not_active Abandoned
- 2010-05-19 AU AU2010250747A patent/AU2010250747B2/en active Active
- 2010-05-19 JP JP2012511414A patent/JP5833545B2/ja active Active
- 2010-05-19 EA EA201171431A patent/EA021832B1/ru not_active IP Right Cessation
- 2010-05-19 SG SG2011077302A patent/SG175304A1/en unknown
- 2010-05-19 CN CN2010800223090A patent/CN102438611A/zh active Pending
- 2010-05-19 CA CA2759674A patent/CA2759674C/en active Active
- 2010-05-19 KR KR1020117030391A patent/KR20120038408A/ko active Application Filing
- 2010-05-19 EP EP10736818.5A patent/EP2432463B1/en active Active
- 2010-05-19 WO PCT/IT2010/000222 patent/WO2010134117A1/en active Application Filing
- 2010-05-19 IT ITRM2010A000255A patent/IT1400312B1/it active
- 2010-05-19 KR KR1020167031463A patent/KR20160132500A/ko active Application Filing
- 2010-05-19 BR BRPI1011103A patent/BRPI1011103B8/pt active IP Right Grant
- 2010-05-19 ES ES10736818.5T patent/ES2555387T3/es active Active
- 2010-05-19 KR KR1020187036782A patent/KR102054942B1/ko active IP Right Grant
- 2010-05-19 MX MX2011012323A patent/MX2011012323A/es active IP Right Grant
-
2011
- 2011-10-24 ZA ZA2011/07764A patent/ZA201107764B/en unknown
- 2011-11-03 IL IL216112A patent/IL216112A/en active IP Right Grant
-
2014
- 2014-05-28 US US14/288,439 patent/US10342826B2/en active Active
-
2019
- 2019-07-08 US US16/504,372 patent/US11524031B2/en active Active
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US5397786A (en) * | 1993-01-08 | 1995-03-14 | Simone; Charles B. | Rehydration drink |
US5389359A (en) * | 1993-06-28 | 1995-02-14 | Miwon Co., Ltd. | Pharmaceutical preparation containing L-aspartate or L-asparagine for preventing ethanol toxicity, and process for preparation thereof |
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