Utility model relates to pharmaceutical production and concerns medicines for treatment of erectile dysfunction.

Erectile dysfunction is condition during which there is noted complications with causing and/or maintenance of erection, early ejaculation. At this time blood does not normally flow in corpora cavernosa of penis or flown blood is not blocked in corpora cavernosa of penis. The mentioned events condition dissatisfaction of men and their sexual partners in their sexual lives. Erectile dysfunction worldwide is noted by 30-50% of men above 40 years of age.

During normal erection, when blood flows in the corpora cavernosa of penis, trabecular tissue compresses the veins of corpora cavernosa and this provides maintenance of erection. Inflow of blood in corpora cavernosa and above mentioned events are provided by nitrogen oxide, which mainly is released from postsynaptic parasympatic neurons. Nitrogen oxide stimulates creation of cyclic guanosine monophosphate (GMP) in corpora cavernosa, and from its part it causes relaxation of smooth muscle cells.

At present for treatment of erectile dysfunction PDE5 inhibitors are widely used, such as sildenafil, tadalafil, vardenafil etc. PDE5 inhibitors strengthen influence of nitrogen oxide in corpora cavernosa, and this provides increasing of blood inflow in corpora cavernosa, especially during sexual stimulation.

Despite of successful use of PDE5 inhibitors in treatment of erectile dysfunction there are the whole range of problems. First of all, they are characterized by dose-depended frequent side effects, such as vision problems (anomaly perception of colors), headache, face redness, nasal obstructions, dizziness, dyspepsia, diarrhea, rash on skin. There shall be also noted that during their long administration it becomes necessary to subsequently increase the dose and this increases also frequency of side effects. Besides, some PDE5 inhibitors, first of all sildenafil, are characterized by short effect, and therefore it shall be administered for several times daily, and this is not recommended. In contrast to the mentioned, some PDE5

SUBSTITUTE SHEET (RULE 26) inhibitors, first of all Tadalafil, are characterized by long period of action, although their activation starts quite late after administration, and of course it creates problems for users, especially during spontaneous, unplanned sexual activities.

From above mentioned aspects it is still actual to provide with medications for treatment of erectile dysfunction which would be activated rapidly, would have long lasting effect and at the same time would have less side effects.

The present utility model provides with therapeutic composition for erectile dysfunction treatment which complies with above mentioned requirements.

The essence of utility model is that composition for erectile dysfunction treatment contains sydenafil citrate and tadalafil as active ingredients, and dicalcium phosphate dihydrate, microcrystalline cellulose, starch sodium glycidolate, colloidal silicon dioxide and magnesium stearate - as pharmaceutically acceptable additives, components with the following proportion in wt. %:

Sydenafil citrate 20-25

Tadalafil 3-5

Dicalcium phosphate dehydrate 50-60

Microcrystalline cellulose 15-20

Starch soda glycolates 3-5

Colloidal silicon dioxide 1-1.5

Magnesium stearate 1-1.5

In the preferred embodiment of utility model the composition has a tablet form.

In the preferred embodiment of utility model the tablet contains components with the following proportion in mg:

Sydenafil citrate 130

Tadalafil 20

Dicalcium phosphate dehydrate 314

Microcrystalline cellulose 100 Starch soda glycolates 24

Colloidal silicon dioxide 6

Magnesium stearate 6

Maximal concentration time of sydenafil citrate in the blood plasma (Tmax) is 1 hour, and half -elimination period (T1/2) makes up 4 hours. Tmax of tadalafil is 2.5 hours, and T1/2 makes up 17 hours. In composition offered by the utility model, combination of above mentioned two ingredients provides rapid effect (about 15-20 minutes) and its long maintenance for about 24 hours (about 24 hours). Further, combination of two active ingredients reduces frequency of side effects.

Combination of two active ingredients in one composition can cause their interaction and also delay of their elimination. Qualitative and quantitative indexes of inactive ingredients existed in the composition offered by utility model provide prevention of interaction of sydenafil citrate and tadalafil and also their unhindered release.

According to the utility model, the composition contains sydenafil citrate and tadalafil as active ingredients, and dicalcium phosphate dihydrate, microcrystalline cellulose, starch sodium glycidolate, colloidal silicon dioxide and magnesium stearate - as pharmaceutically acceptable additives, components with the following proportion in wt. %:

Sydenafil citrate 20-25

Tadalafil 3-5

Dicalcium phosphate dehydrate 50-60

Microcrystalline cellulose 15-20

Starch soda glycolates 3-5

Colloidal silicon dioxide 1-1.5

Magnesium stearate 1-1.5

In the preferred embodiment of the utility model, the composition has a tablet form.

In the preferred embodiment of the utility model, the tablet contains components with the following proportion in mg: Sydenafil citrate 130

Tadalafil 20

Dicalcium phosphate dehydrate 314

Microcrystalline cellulose 100

Starch soda glycolates 24

Colloidal silicon dioxide 6

Magnesium stearate 6

Tablet can be prepared in pharmaceutical production by commonly known method, preferentially, by wet granulation.

Indication for use of the tablet is erection dysfunction of any etiology.

Tablet dosage is V tablet once daily. Tablet is administered 15-20 minutes before sexual act.

Example:

There were mixed 1.3 kg sydenafil citrate, 200 mg tadalafil, 3.14 dicalcium phosphate dihydrate, 1 kg microcrystalline cellulose and 240 mg starch soda glycolates powders. After well mixing the mixture was poured 140 liters of water and mixed well again. In result the obtained mixture was conducted wet granulation and then drying. After drying obtained granules were mixed with 60 mg colloidal silicon dioxide powder and 60 mg of magnesium stearate powder. Obtained mixture was sorted in 600-600 mg capacities and were tableted by the method of direct pressing. In result there were obtained ten 600 mg tablets.

Efficiency study

Efficiency of tablet offered by the utility model was studied on 15 rabbits, which were divided in three equal groups. First group was orally administered 14 of the tablet offered by utility model. The second group was orally administered Viagra (sydenafil) tablet of 25 mg dose. Third group was orally administered Sialis (Tadalafil) tablet of 5 mg dose.

After administration of medications there were studied time of starting of erection, maximal erection achievement time and erection maintenance time.

Data of experiments are mentioned in the table 1. Table 1

As it is seen from the data given in the table 1, offered medication is obviously more effective as from the standpoint of erection start, so from the standpoint of maximal erection achievement and erection maintenance time.

Efficiency was also studied in 15 volunteer men aged 40-50, who were noted erection dysfunction caused by various reasons. Volunteers were divided into three equal groups. Division was realized so that persons with equal parameters in all groups were equally divided. One group was administering Vi tablet offered by utility model once daily for two weeks, the second group was administering Viagra (Sydenafil) tablet of 100 mg dose once daily for two weeks, and the third group was administering Sialis (tadalafil) tablet of 20 mg dose, once daily for two weeks.

After two weeks the volunteers were questioned and there was defined international index of their erection function (IIEF).

Questioning results are given in the table 2.

Table 2 As it is seen from the data given in the table 2, criteria of estimation of offered medication is significantly higher compared to Viagra and Sialis.

Study of side effects

Side effects were studied in 30 volunteer men aged 30-40. Volunteers were divided into three equal groups. Division was realized so that persons with equal parameters in all groups were equally divided. One group was administering Vi tablet offered by utility model once daily for two weeks, the second group was administering Viagra (Sydenafil) tablet of 100 mg dose once daily for two weeks, and the third group was administering Sialis (tadalafil) tablet of 20 mg dose, once daily for two weeks.

After administration of medications there were studied percentage index of side effects in each group.

Received data are given in the table 3.

Table 3

As it is seen from the data given in the table, offered medication is characterized by too less frequency of side effects than Viagra and Sialis.

Therefore, composition, offered by utility model, is effective, safe medication for treatment of erection dysfunction.