Pharmaceutical composition including choline alfoscerate and hopantenic acid (or its salt) for treatment of cerebral circulatory insufficience and erectal dysfunction

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine and pharmaceutical industry and represents pharmaceutical combination for treatment of cerebral circulatory insufficiency and psychodependent form of erectile dysfunction, including choline alfoscetate in amount 50-600 mg per one intake and hopantenic acid or its pharmaceutically acceptable salt in amount 20-800 mg per one intake.

EFFECT: invention ensures reduction of frequency, duration and intensity of headache, dizziness, fatigability, irritability, improvement of memory for current events and sleep, as well as increase of erectile dysfunction (ED), reduction and fixation of stable positive motivation for quality erection and full orgasm in case of psychodependent form of ED; simultaneously, due to manifestation of synergic effect, which results from the use of claimed combination, it became possible to reduce day dose of hopantenic acid or its salt from 1,5 mg to 0,5 mg.

12 cl, 4 ex, 24 tbl, 4 dwg

 

The invention relates to pharmaceutical combinations of choline alfoscerate and guantanomo acid (in the form of pharmaceutically acceptable salts, and pharmaceutical compositions comprising such combinations. This invention also relates to the use of the pharmaceutical combination of choline alfoscerate and guantanomo acid (in the form of pharmaceutically acceptable salts) for treatment of patients with initial signs of circulatory failure, brain (initial presentation of inadequate and developing as a consequence of erectile dysfunction.

The most important manifestations of aging are the result of age-related brain changes. In Russia over the last decade has been a trend manifestations of the symptoms of premature aging associated with chronic social stress. One of the manifestations of the effects of chronic social stress is erectile dysfunction (ED).

The term "erectile dysfunction" is commonly used to describe ongoing or recurring inability to achieve and/or maintain sufficient for sexual intercourse, the penile erection. The use of this term today, are preferred because such traditional terms as "impotence" or "male impotence", lack specific the path and derogatory additional value for the patient.

Erectile dysfunction may be the cause of several types of endocrine, medical, local, neurological and vascular. All this relates to organic form ED when it is due to some change or disorder in the body.

Much more common psychological form of erectile dysfunction, in which a normal sex life prevents exclusively psychoneurological features of the man. In addition, almost always problems with erectile dysfunction due to organic causes, added a psychological component, which after elimination of the root cause may go in the first place.

After removal of the major urological reasons that causes ED (for example, prostitutie infectious origin)remain psihonevroticheskih with a dominant focus complex work conditionally unconditional reflexes in prefrontal cortical urogenital areas of the brain, which reduces the positive motivation on the quality of erection.

Currently, there are only few works on cerebral vascular potentials at initial presentation of inadequate, despite the fact that the pathological changes in the cerebral circulation are the primary pathogenetic factor in the development of initial presentation of inadequate (Vthokie, Nowonmai. The energetic physiology of the brain. - M.: The Antidoron, 203).

There is a method of treatment of psychogenic disorders of erectile function in men (WO 95/28930, 1995), involving the use of sublingual dosage forms of apomorphine. The claimed dosage forms contain from about 2.5 to 10 mg of apomorphine, dissolve in water over a period of time from about 2 to 10 minutes and do not cause the nausea or other side effects typical of apomorphine. However, this patent does not show any relationship between circulatory insufficiency of the brain and erectile dysfunction.

The present invention is the creation and use of a combination cerebroprotective and nootropic of biologically active substances for the treatment of circulatory failure, brain and pharmacological correction psychosasami form ED.

The problem is solved in that the proposed pharmaceutical combination containing an effective amount of choline alfoscerate and guantanomo acid (in the form of its pharmaceutically acceptable salts).

The task of the invention is solved by a pharmaceutical composition comprising a combination of choline alfoscerate and guantanomo acid (and salts) and pharmaceutically acceptable additives. The pharmaceutical composition of the present invention can be performed in various dosage forms is x, including in the form of tablets, coated tablets, sublingual tablets, hard gelatin capsules, soft gelatin capsules, granules for the preparation of oral suspension.

The claimed combination of drugs (substances) can be used for the treatment of migrated or are in remission urogenital diseases in patients, in particular erectile dysfunction. The majority of patients with ED suffer zerebrasteniceski syndrome mixed Genesis (vascular-social), and after suffering various forms of pathology of the prostate gland.

The technical result of the invention is the improvement of cerebral neurological symptoms: decrease in the frequency, duration and intensity of headache, dizziness, fatigue, irritability, memory on current events and sleep, as well as improving the quality of life in patients with ED: increase in erectile activity, decrease nervousness and securing stable positive motivation for quality erections and a full orgasm.

Alfostserat - choline hydroxide (R)-2,3-dihydroxybergamottin (internal salt) has a neuroprotective effect: stimulates cholinergic receptors, mainly in the Central (has a cholinomimetic effect). Stimulates cholinergic is eurotransbio, improves the plasticity of neuronal membranes and function of receptors, activates cerebral blood flow, stimulates the metabolism of the Central nervous system and reticular formation (encyclopedia of drugs. 11 vol., M, RLS - 2004, s).

Medicines choline alfoscerate used with traumatic brain injury (acute period) mainly stem the level of the lesion, chronic cerebrovascular insufficiency (dyscirculatory encephalopathy), dementia (medical literature type, senile, mixed forms), ischemic stroke (recovery period), trochaic's disease, functional disorders of the Central nervous system, impaired memory, confusion, disorientation, decreased motivation, initiative and concentration, senile melancholia.

Single dose of choline alfoscerate after oral administration of 400 mg and placed 3 times a day.

Gopantenova acid-(R)-4-[(2,4-dihydroxy-3,3-dimethyl-1-oxobutyl)amino]butane acid (as calcium salt) has a neuroprotective effect: has a stimulating effect on the Central nervous system cerebral insufficiency exogenous-organic Genesis. Improves efficiency, stimulates mental activity, reduces motor anxiety manage the behavior, has anticonvulsant action. Applies when umst is authorized retardation, delays in speech and mental development, Serebryanicheskaya syndrome to correct the side effects of antipsychotic drugs, including antipsychotic extrapyramidal syndrome, epilepsy (in complex therapy), residual manifestations transferred neuroinfections, postvaccinal encephalitis, traumatic brain injury, cerebral organic insufficiency in patients with schizophrenia (in complex therapy), hyperkinesia, disorders of urination (enuresis, daytime incontinence, pollakiuriya, urgent desires, etc.) (encyclopedia of drugs. 11 vol., M, RLS - 2004, s.257).

Daily dose guantanomo acid (in the form of calcium salt) oral adults is 1.5 to 3 g

The components of the claimed combination may be administered in separate dosage forms or combined single drug.

Single dose components can vary for choline alfoscerate from 50 to 600 mg at one time and guantanomo acid (and salts) from 20 to 800 mg per intake. Dosage is determined by body weight and age of the patient, method of administration or the nature of therapeutic formulation, and the nature of the treatment, other drugs.

A significant factor contributing to neurodegeneration during initial presentation of inadequate is the change in acid-base is on balance (COB), which increases free radical and exitotoxicity processes. Restoration of blood supply should also contribute to the normalization of acid-base balance.

Non-invasive electrophysiological method that gives a relative measure COB, the level of constant potential brain (SCP). SCP in its origin is the vascular capacity, mainly potential blood-brain barrier, while the main potenzialanalysen ion is hydrogen ion. Because cerebral circulation insufficiency accompanied by changes in acid-base balance of the brain tissue, the use of the method of registration SCP allows us to estimate the cerebral circulation insufficiency in major vascular pools brain. (Vthokie, Nowonmai. The energetic physiology of the brain. M: the Antidoron, 2003, page 11). The emphasis of the research done on the area of the cortical projection of the center of erection in the front of the connecting artery.

To assess the characteristics of cerebral blood flow in patients with initial presentation of inadequate and ED before and after using the pharmaceutical combination of choline alfoscerate and guantanomo acid (and salts) were used to check level of constant potential (SCP) brain-computer-hardware complex "N is greenerhomes-3, for most patients was also used magnetic resonance imaging (MRI) and positronemission tomography (PET).

The study involved patients with initial presentation of inadequate and ED-patients of middle age with symptoms of premature aging of the brain, only 43 people. Check UPP was carried out in five leads: frontal, Central, occipital and two temporal right and left (Fz, Cz, Oz, Td, Ts) scheme 10-20. The projection areas of the Desk SCP correspond to major vascular pools: the anterior cerebral, middle cerebral and vertebral arteries. The patients were examined twice: before and after monotherapy claimed combination of choline alfoscerate 400 mg and guantanomo acid 250 mg twice daily in the morning and in the afternoon up to 17 hours for 28-30 days.

During treatment, patients were examined by a neurologist and urologist, which was estimated change UPP, General condition (mood, headache, fatigue, nervousness, blood pressure etc), conducted a blood test and was given a subjective rating with positive dynamics of erection and achieve orgasm during intercourse.

The distribution of SCP before treatment testified to the change in cerebral blood flow mainly in the basins of the anterior and middle brain is th artery.

The following are examples of implementation of the invention the pharmaceutical combination.

Example 1.

The patient M, male, 50 years. Initial signs of initial presentation of inadequate and ED.

Tserebroastenicheskie syndrome mixed Genesis, which is expressed in the form of ED.

Complaints (in points) neurological 1-5:

where 1 - mild, 5 - selenopyran

ComplaintsBefore the treatmentAfter the treatment
Headache32
The memory impairment31
Dizziness10
Insomnia21
Irritability21

Complaints (in points) urological 1-5:

where 1 - no effect, 5 - positive effect

Before the treatmentAfter the treatment
34
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Example 2.

Patient R., male, 40 years. Initial signs of initial presentation of inadequate and ED.

Tserebroastenicheskie syndrome mixed Genesis, which is expressed in the form of ED.

Complaints (in points) neurological 1-5:

where 1 - mild, 5 - selenopyran

ComplaintsBefore the treatmentAfter the treatment
Headache21
The memory impairment21
Dizziness00
Insomnia11
Irritability31

Complaints (in points) urological 1-5:

where 1 - no effect, 5 - positive effect

Before the treatmentAfter the treatment
35

Example 3.

The patient. With, male, 46 years old. Initial signs of initial presentation of inadequate and ED.

Tserebroastenicheskie si the drôme mixed Genesis, expressed in the form of ED.

Complaints (in points) neurological 1-5:

where 1 - mild, 5 - selenopyran

ComplaintsBefore the treatmentAfter the treatment
Headache31
The memory impairment31
Dizziness20
Insomnia11
Irritability32

Complaints (in points) urological 1-5:

where 1 - no effect, 5 - positive effect

Before the treatmentAfter the treatment
34

Example 4.

Patient T., male, 62 years old. Initial signs of initial presentation of inadequate and ED.

Tserebroastenicheskie syndrome mixed Genesis, which is expressed in the form of ED.

Complaints (in points) neurological 1-5:

where 1 - mild, 5 - SIL is vyrazhennye

ComplaintsBefore the treatmentAfter the treatment
Headache31
The memory impairment21
Dizziness10
Insomnia11
Irritability21

Complaints (in points) urological 1-5:

where 1 - no effect, 5 - positive effect

Before the treatmentAfter the treatment
23

Example 5.

Patient F., male, 66 years old. Initial signs of initial presentation of inadequate and ED.

Tserebroastenicheskie syndrome mixed Genesis, which is expressed in the form of ED.

Complaints (in points) neurological 1-5:

where 1 - mild, 5 - selenopyran

Complaints Before the treatmentAfter the treatment
Headache31
The memory impairment11
Dizziness21
Insomnia11
Irritability32

Complaints (in points) urological 1-5:

where 1 - no effect, 5 - positive effect

Before the treatmentAfter the treatment
35

Comparison of data obtained during the registration SCP, led to the conclusion that a violation of arterial inflow often accompanied by a decrease in the energy metabolism of the brain and the relative alkalosis, and impaired venous outflow leads in most cases to acidotic shifts COB.

Figure 1 presents the distribution of SCP in a patient with initial presentation of inadequate and ED before treatment, figure 2 - after treatment.

Figure 3 presents a graph of the PP brain in patients with initial presentation of inadequate and ED Central Genesis before and after the cerebroprotective therapy claimed combination (averaged data for all patients). On the y - axis values of SCP in millivolts (mV), the abscissa axis is different lead UPP before and after treatment (1F - front diversion, 2C - Central leads (frontal), 3O - occipital (occipital), 4Td right temporal abstraction, 5Ts - left temporal abstraction, 6Td-Ts - hemispheric relationships (arithmetic difference between the potentials). It is seen that after the treatment SCP brain has shifted to acid-base balance on the scale of age-specific norms, namely in the direction of its age harmonisation.

Figure 4 presents the severity of symptoms initial presentation of inadequate (in points) to (column 1) and after treatment (column 2) (averaged data for all patients).

Figure 5 displays the dynamics of erectile activity (in points) to (column 1) and after treatment (column 2) (averaged data for all patients). After the treatment claimed by the combination of erectile activity increased.

The data obtained (figure 5) obratnoproportsionalno correlated with a decrease in the severity of symptoms initial presentation of inadequate (figure 4): when reducing the severity of symptoms initial presentation of inadequate improved erectile activity.

During the preliminary studies, the data on the assimilation of choline alfoscerate in the blood (6). In animal experiments, the following data: joint application of choline, altho the cerate and guantanomo acid (and salts) leads to high assimilation of choline alfoscerate in the blood, level which far exceeds the level of assimilation of the latter in the case of the use of one of choline alfoscerate.

This fact suggests that the synergism that is manifested by joint application of choline alfoscerate and guantanomo acid, leads to a high degree of bioavailability of choline alfoscerate that are not noted in the individual application of this component. The degree of concentration of choline alfoscerate in the blood not only provides long term effect, but its more full suction, and together higher bioavailability and bioeffectives administered drugs.

Due to the manifestations of the synergistic effect that occurs when using the claimed combination, it was possible to reduce the daily dose guantanomo acid (or its salts) with 1.5-3 g to 0.5 g

Another object of the invention is a pharmaceutical composition combined drug choline alfoscerate and guantanomo acid (and its salts).

The pharmaceutical compositions of the present invention can be made in the form of tablets, coated tablets, hard and soft gelatin capsules, granules for the preparation of suspensions.

The pharmaceutical compositions according to the invention in addition to the active principles contain one or more pharmaceutical is Eski acceptable carriers or excipients.

Among pharmaceutically acceptable excipients can be listed, not limited volume of claims, the binder thinners, dezintegriruetsja agents, stabilizers, preservatives, lubricants, aromatic and flavoring or sweeteners.

Each dosage form contains the recommended dose of active substances: 50-600 mg of choline alfoscerate and 20-800 mg acid guantanomo acid or salt guantanomo (for example, calcium salts or other). Alfostserat as an active ingredient can be used both in liquid and in solid form (powder, granules).

The following examples illustrate the implementation of the invention in the form of various dosage forms combined drug.

TABLETS

Example 1 (wet granulation)

ComponentsNumber
mgmg
Alfostserat liquid100200
Acid gopantenova100200
Colloidal silicon dioxide 510
Lactose95190
Microcrystalline cellulose150300
Polyvinylpyrrolidone3060
Magnesium stearate510
Carboximetilkrahmal1530

Alfostserat is a low-melting product with a melting point of 28°C. In the proposed implementation of the substance with water content up to 14% of the melting temperature is reduced to room temperature. Therefore, before the introduction of solid dosage forms of the product is mixed with colloidal silica and a part of the LCC education engineering powder.

Tablets produced by wet granulation. Prepare the granulate composition: acid gopantenova, lactose, microcrystalline cellulose as a binding solution using a solution of low molecular weight polyvinylpyrrolidone. The obtained wet mass is calibrated and dried. The dried granulate is calibrated and is mixed in the mixer for su is their mixtures with powder choline alfoscerate oxide of silicon and MCC. The obtained granulate outrivals a mixture of dried carboxymethyl amylum, magnesium stearate in the mixer for dry mixes. The resulting mass tabletroute on a tablet press (option 1).

Example 2 (direct pressure).

ComponentsNumber
mgmg
Alfostserat powder100200
Acid gopantenova200400
Lactose100200
Microcrystalline cellulose75150
Crosspovidone1530

Colloidal silicon dioxide510
Magnesium stearate510

Tablets obtained by direct press is for. All the ingredients are mixed in the mixer for dry mixtures, the mixture tabletirujut.

Example 3 (wet granulation)

ComponentsNumber
mgmg
Alfostserat liquid100200
Acid guantanomo ferocity100200
Colloidal silicon dioxide510
Lactose95190
Microcrystalline cellulose150300
Polyvinylpyrrolidone3060
Magnesium stearate510
Carboximetilkrahmal1530

Tablets produced by the method described in the example is 1.

Example 4 (direct pressure).

ComponentsNumber
mgmg
Alfostserat powder100200
Acid guantanomo ferocity200400
Lactose100200
Microcrystalline cellulose75150
Crosspovidone1530
Colloidal silicon dioxide510
Magnesium stearate510

Tablets produced by direct pressing method described in example 2.

The COATED TABLETS

The composition of the shell 1

ComponentsIf estvo, wt.%
Titanium dioxide7,500
Oxypropylation50,000
Polyvinylpyrrolidone weight25,000
The polyethylene glycol10,000
Talc7,500
Water q.s.

The composition of the shell 2

ComponentsNumber, wt.%
Sucrose56,30
Kollidon 30to 5.93
Titanium dioxideto 6.67
Calcium carbonateto 6.67
Talc21,48
Glycerin2,96
Dye (Sicovit) q.s., to obtain a desired color
Water q.s., to obtain suspension

Tablets-kernel, the scientists one of the previously listed methods and compositions dedust. Prepare a water suspension of the above-mentioned composition and is applied in the apparatus for coating by spraying on tablets-kernel.

The composition of the shell 3

ComponentsNumber, wt.%
Kollidon VA 6421,03
Macrogol 60004,76
The hypromellose31,35
Titanium dioxide14,29
Cikovic7,14
Talc21,43
Water q.s., to obtain suspension

Tablet cores obtained one of the foregoing methods and compositions, dedust. Prepare a solution composition (in parts): kollidon VA64 (4,42), macrogol 6000 (1,00), hypromellose (6,58), purified water (61,00). Preparing a suspension of the composition of titanium dioxide (2,00), cicovic (1,00), talc (3,00), water (12,11). The resulting aqueous solution and the suspension mixed. Dedusted tablets-engine cover obtained by suspension in the apparatus for coating the JV is the FDS spray.

CAPSULES HARD GELATIN

Mass for encapsulation receive one of the ways to obtain masses for tabletting described in pills or following examples. The resulting mixture is dispensed into hard gelatin capsules at capsulearava machine.

Part 1

ComponentsNumber
mgmg
Alfostserat liquid100200
Acid gopantenova100200
Colloidal silicon dioxide510
Lactose95190
Microcrystalline cellulose150300
Polyvinylpyrrolidone3060
Magnesium stearate510
Carboximetilkrahmal1530

Option 2

Receive the tablets of the following composition:

28
Componentsmgmg
Choline allposters powder50100
Lactose100200
Corn starch2856
Kollidon VA 641224
Kollidon CL612
Magnesium stearate24
Colloidal silicon dioxide24
Acid Kopaneva100200
Lactose50100
Corn starch56
Kollidon VA 641224
Kollidon CL612
Magnesium stearate24
Colloidal silicon dioxide24

Get tablets choline alfoscerate wet granulation. Prepare the granulate composition: alfostserat, lactose, starch as a binding solution using an aqueous solution of kollidon VA 64. The obtained wet mass is calibrated and dried. The dried granulate is calibrated and outrivals mixture kollidon CL, magnesium stearate and Aerosil.

Get tablets acid guantanomo wet granulation. Prepare the granulate composition: acid gopantenova, lactose, starch as a binding solution using an aqueous solution of kollidon VA 64. The obtained wet mass is calibrated and dried. The dried granulate is calibrated and outrivals mixture kollidon CL, magnesium stearate and Aerosil.

The obtained tablets choline alfoscerate and acid guantanomo dedust and put one tab is etce choline alfoscerate and acid guantanomo in hard gelatin capsules at capsulearava machine.

TABLETS SUBLINGUAL

Part 1

ComponentsNumber
mgmg
Alfostserat powder100200
Acid gopantenova100200
Sorbitol for direct compression (Parteck SI)9797
Stearyl-fumarate sodium33

Part 2

ComponentsNumber
mgmg
Alfostserat powder100200
Acid guantanomo fumarate100200
Sorbitol for direct compression (Parteck SI)97 97
Stearyl-fumarate sodium33

Tablets produced by direct pressing. The filler used ready mix sorbitol (Parteck). All the ingredients are mixed in dry form and tabletirujut.

GRANULES FOR PREPARATION of ORAL SUSPENSION

Part 1

ComponentsNumber
mgmg
Alfostserat powder100200
Acid gopantenova100200
Sorbitol95190
Stearyl-fumarate sodium510
Sucrose200400

Part 2

ComponentsNumber
the g mg
Alfostserat powder100200
Acid gopantenova100200
Sorbitol100200
Stearyl-fumarate sodium510
Kollidon CL-M1530
Fructose162,9325,8
Kollidon 90 F1530
Flavoring (banana)24
Sodium salt of saccharin0,10,2

Part 3

ComponentsNumber
mgmg
Alfostserat powder 100200
Acid guantanomo potassium salt100200
Sorbitol100200
Stearic-fumarate sodium510
Kollidon CL-M1530
Fructose162,9325,8
Kollidon 90 F1530
Flavoring (banana)24
Sodium salt of saccharin0,10,2

Components are mixed in the mixer, the resulting product is metered into the jars (bottles) or single dose packets (contour buzyakova packaging).

SOFT GELATIN CAPSULES

The stability of the content of the capsule is achieved by using as fillers and stabilizers suspensions of the active substances of polyethylene glycol and/or propylene glycol with different molecular weight, the/or glycerin in an amount of from 1 to 50%, as suspensorysex or dispersing agents, water and/or ethyl alcohol.

When this capsule shell as plasticizers may include polyhydric alcohols and/or partially hydrogenated polyhydric alcohols: glycerol and/or propylene glycol and/or sorbitol, and/or a mixture of sorbitol/sorbitan in any ratio, and/or Inositol, and/or mannitol and/or xylitol in an amount of from 10 to 70% by weight of the capsule's shell.

Thus, the shell may contain other auxiliary substances (dyes, pigments, antioxidants and preservatives). As preservatives can be used, for example, potassium sorbate, ethylparaben, methylparaben, propylparaben and other

Part 1

ComponentsNumber
mgmg
Alfostserat liquid200400
Acid gopantenova100200
Glycerin2550
PEG 40010 20
Ethyl alcohol 95%510
Purified water75150
The composition of the shell
gelatin45,591
glycerin10,521
sorbitol10,521
Purified water33,567
Dyes or pigments0,220,44
(titanium dioxide, iron oxides, and others)
Preservatives and antioxidants (nipagin, nipazol and others)0,1050,21

Charged to the reactor water clean and glycerin, mixed using a stirrer for 10 minutes Substance choline alfoscerate loaded into the reactor when the stirrer, with whom spengiu stirred for 20 minutes To the resulting suspension add acid Guantanamo and again stirred for 20 minutes

Preparation of a gelatinous mass.

In the apparatus for preparing a gelatinous mass pour purified water, vacuum, add the glycerin, stir while heating, then download sorbitol (in the form of a solution or solid), stirred under heat, add gelatin and preservatives, mix the mass when heated within 20-40 minutes

Stabilization of the gelatinous mass is performed not more than 24 hours Then hold staining gelatinous mass pre-prepared aqueous solution or aqueous suspension of the required dye. Spend filling capsules in the capsule machine.

Part 2

ComponentsNumber
mgmg
Alfostserat liquid200400
Acid gopantenova100200
Glycerin2040
PEG 30010
Purified water75150
The composition of the shell
gelatin45,591
glycerin10,521
sorbitol/sorbent10,521
Purified water33,567
Dyes or coloring pigments (titanium dioxide, iron oxides, and others)0,220,44
Preservatives and antioxidants (nipagin, nipazol and others)0,1050,21

Charged to the reactor water clean and glycerin, mixed using a stirrer for 10 minutes Substance choline alfoscerate loaded into the reactor with the agitator, the suspension is stirred for 20 minutes To the resulting suspension add acid Guantanamo and again stirred for 20 minutes

Preparation of gelatin is howling mass.

In the apparatus for preparing a gelatinous mass pour purified water, vacuum, add the glycerin, stir while heating, then download sorbitol/sorbitan in the form of a solution or solid substances (for example, Sorbitol Sorbitan Solution, USP or EP, or Anidrisorb or other), stirred under heat, add gelatin and preservatives, mix the mass when heated within 20-40 minutes

Stabilization of the gelatinous mass is performed not more than 24 hours Then hold staining gelatinous mass pre-prepared aqueous solution or aqueous suspension of the required dye. Spend filling capsules in the capsule machine.

Part 3

ComponentsNumber
mgmg
Alfostserat liquid200400
Acid gopantenova100200
Glycerin2550
Purified water75150
The composition of the shell
gelatin45,591
Inositol10,521
sorbitol/sorbent10,521
Purified water33,567
Dyes or coloring pigments (titanium dioxide, iron oxides, and others)0,220,44
Preservatives and antioxidants (nipagin, nipazol and others)0,1050,21

Charged to the reactor water clean and glycerin, mixed using a stirrer for 10 minutes Substance choline alfoscerate loaded into the reactor with the agitator, the suspension is stirred for 20 minutes To the resulting suspension add acid Guantanamo and again stirred for 20 minutes

Preparation of a gelatinous mass.

In the apparatus for preparing a gelatinous mass pour purified water, vacuum, add Inositol, stirred under heating, then download from the of Bicol/sorbitan (for example Sorbitol Sorbitan Solution USP or EP, or Anidrisorb or other), stirred under heat, add gelatin and preservatives, mix the mass when heated within 20-40 minutes

Stabilization of the gelatinous mass is performed not more than 24 hours Then hold staining gelatinous mass pre-prepared aqueous solution or aqueous suspension of the required dye. Spend filling capsules in the capsule machine.

Part 4

ComponentsNumber
mgmg
Alfostserat liquid200400
Acid gopantenova100200
Glycerin2550
Purified water75150
The composition of the shell
gelatin45,591
Inositol the 5.2510,5
mannitolthe 5.2510,5
sorbitol/sorbent10,521
Purified water33,567
Dyes or coloring pigments (titanium dioxide, iron oxides, and others)0,220,44
Preservatives and antioxidants (nipagin, nipazol and others)0,1050,21

Charged to the reactor water clean and glycerin, mixed using a stirrer for 10 minutes Substance choline alfoscerate loaded into the reactor with the agitator, the suspension is stirred for 20 minutes To the resulting suspension add acid Guantanamo and again stirred for 20 minutes

Preparation of a gelatinous mass.

In the apparatus for preparing a gelatinous mass pour purified water, vacuum, add Inositol and mannitol, and stirred under heating, then download sorbitol/sorbitan (for example, Sorbitol/sorbitan solution USP/NF, BP or EP, or TM Anidrisorb or Polisorb, or Sorbitol Special, or other), paramashiva the t when heated, add gelatin and preservatives, mix the mass when heated within 20-40 minutes

Stabilization of the gelatinous mass is performed not more than 24 hours Then hold staining gelatinous mass pre-prepared aqueous solution or aqueous suspension of the required dye. Spend filling capsules in the capsule machine.

Part 5

ComponentsNumber
mgmg
Alfostserat liquid200400
Acid guantanomo potassium salt100200
Glycerin2550
PEG 4001020
Ethyl alcohol 95%510
Purified water75150
The composition of the shell
gelatin45,591
glycerin10,521
sorbitol10,521
Purified water33,567
Dyes or coloring pigments (titanium dioxide, iron oxides, and others)0,220,44
Preservatives and antioxidants (nipagin, nipazol and others)0,1050,21

1. Pharmaceutical combination for the treatment of circulatory failure, brain and psychosasami form of erectile dysfunction, including alfostserat in the number of 50-600 mg at one time and Guantanamo acid (in the form of pharmaceutically acceptable salts) in the amount of 20-800 mg at one time.

2. The pharmaceutical combination according to claim 1, characterized in that it includes choline alfoscerate 400 mg and guantanomo acid (or its pharmaceutically acceptable salt) 250 mg at one time.

3. The pharmaceutical combination according to claim 1, characterized in that alfostserat and gopantenova acid is the same (or its salt) is entered as separate dosage forms.

4. The pharmaceutical combination according to claim 1, characterized in that alfostserat and gopantenova acid (or its salt) are introduced in the form of a single dosage form.

5. Pharmaceutical composition for treating circulatory insufficiency of the brain and psychosasami form of erectile dysfunction, which includes a combination according to claim 1 in an effective amount and a pharmaceutically acceptable additive.

6. The pharmaceutical composition according to claim 5, characterized in that it is made in the form of granules for the preparation of oral suspension.

7. The pharmaceutical composition according to claim 5, characterized in that it is made in tablet form.

8. The pharmaceutical composition according to claim 5, characterized in that it is made in the form of a capsule.

9. The pharmaceutical composition according to claim 7, characterized in that it is made in the form of coated tablets.

10. The pharmaceutical composition according to claim 7, characterized in that it is made in the form of sublingual tablets.

11. The pharmaceutical composition of claim 8, wherein the capsule is a hard gelatin capsule.

12. The pharmaceutical composition of claim 8, wherein the capsule is a soft gelatin capsule.



 

Same patents:

FIELD: medicine.

SUBSTANCE: methods according to the invention consist in introducing an Aβ 16-23 fragment having an amino acid sequence KLVFFAED of 16-23 residues SEQ ID NO:1. Besides the invention concerns the Aβ 16-23 fragment and a pharmaceutical composition containing it.

EFFECT: feasible prevention and treatment of Alzheimer's disease ensured by inhibition of amyloid deposition in cerebrum.

72 cl, 2 dwg, 1 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to neurology, and can be used in treating the patients with multiple sclerosis. That is ensured by infusion of rituximab in a dose 1 g followed by introduction of mitoxantrone in a dose 20 mg and another infusion of rituximab in a dose 1 g 13-15 days later. A common preanaesthetic medication precedes infusion of rituximab.

EFFECT: method ensures fast therapeutic effect and prolonged remission in all forms of multiple sclerosis without a concomitant therapy, including chemotherapy.

1 ex, 11 dwg

FIELD: chemistry.

SUBSTANCE: present invention relates to new compounds of formulae and , in which radicals and symbols assume values defined in the formula of invention, e.g. to 1H-indazoles, 1,2-benzisoxazoles and 1,2-benzisothiazoles. Said compounds are receptor ligands of the α-7 nAChR subtype. The invention also relates to a pharmaceutical composition containing the said compounds.

EFFECT: possibility of using the said compounds to make medicinal agents for treating diseases associated with impaired functioning of nicotinic acetylcholine receptors and their abnormal functioning, primarily in brain cells.

46 cl, 85 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: according to the invention, a pharmaceutical composition contains aripiprazole metabolite combined with serotonin reuptake inhibitor. Aripiprazole metabolite is chosen from dehyoaripiprazole DM-1458, DM-1451, DM-1452, DM-1454 or DCPP. Aripiprazole metabolite is a stabiliser of dopamine-serotonin system. Serotonin reuptake inhibitor can be fluoxetine, duloxetine, venlafaxine, milnaciprane, citalopram, fluvoxamine, paroxetin, sertraline or escitalopram and their salts. The pharmaceutical composition contains one weight part of said aripiprazole metabolite and 0.01 to 50 weight parts of said serotonin reuptake inhibitor. The pharmaceutical composition under the invention can be used for treating the patients with phrenopathies, particularly with depression or major depressive disorder.

EFFECT: pharmaceutical composition is effective and does not cause by-effects.

22 cl, 8 dwg, 3 tbl, 9 ex

FIELD: medicine.

SUBSTANCE: invention relates to medical agents and concerns a remedy in the form of an injection precursor product for obtaining liquid injectable composition, containing as agent for prevention and/or treatment of neurodegenerative diseases, nervous disorders or diseases requiring nerves regeneration the effective quantity of (2R)-2-propyloctane acid or salt thereof, and 1-5 equivalents of the basic ion of metal as per 1 equivalent of (2R)-2-propyloctane acid or salt thereof, metal salt selected from phosphoric acid metal salt, carbonic acid metal salt, and sulfurous acid metal salt and may optionally contain metal hydroxide as the source(s) of the basic metal ion.

EFFECT: development of the remedy which is resistant to pH fluctuations and does not grow turbid at solution.

21 cl, 3 dwg, 21 tbl, 22 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel naphthalene derivatives of general formula I , as well as to their pharmaceutically acceptable salts, which can be used for treating and/or preventing diseases associated with H-3 receptor modulation. In formula I, R1 is selected from hydrogen, lower alkyl, phenyl, phenyl-lower alkyl and lower alkoxyalkyl; R2 is selected from hydrogen, lower alkyl, C3-C7-cycloalkyl, lower alkoxyalkyl or lower alkylsuphanylalkyl (all values of R1 and R2 are given in the formula of inventions); or R1 and R2 together with the nitrogen atom to which they are bonded form a 4-7-member saturated or partially unsaturated heterocyclic ring which can contain one more heteroatom selected from nitrogen, oxygen and sulphur atoms, where the said heterocyclic ring can be unsubstituted or substituted with 1-2 groups, or can be condensed with an unsubstituted phenyl ring; A is selected from (values of R3-R7, R9, R10, X, m, n, t, p, q and s are given in the formula of invention). Invention also pertains to a pharmaceutical composition containing formula I compounds.

EFFECT: increased effectiveness of application.

30 cl, 2 tbl, 188 ex

FIELD: medicine.

SUBSTANCE: therapeutically effective amount of a proteosome composition containing a preparation of outer membrane protein of gram-negative bacteria.

EFFECT: reduced amyloid deposit ensured by activated microglial phagocytosis without induction of neurotoxic effects.

17 cl, 9 dwg, 4 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to neonatology, and can be used in treatment of newborns who are on ILV in critical state, conditioned by perinatal affection of central nervous system. For this purpose preliminarily rate of blood flow in vein of Galen is determined by dopplerography. If rate of blood flow decreases lower than 4 cm/s, inhalation with nitrogen oxide in concentration 15 ppm during 24 hours is carried out.

EFFECT: method allows to considerably reduce lethality of newborns in case of said pathology due to respiratory therapy with nitrogen oxide which is endothelial relaxing factor, and in case of introduction through inhalation - selective pulmonary vasodilatator.

3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) , where A, B represent C; D is selected from N; X is selected from -CRaRb-, -O-; Y is selected from O; Z1 and Z2 are independently selected from hydrogen, substituted or unsubstituted alkyl having 1-8 atoms, R1-R4 are independently selected from hydrogen or halogen; R5-R16 independently represent hydrogen; where Ra and Rb independently represent hydrogen; n equals 1-3; m equals 0 or 1, k equals 2; or to pharmaceutically acceptable salts or solvates of the said compounds. The invention also relates to a pharmaceutical composition based on the said compounds which inhibits butyrylcholin esterase (BuChE).

EFFECT: obtaining novel compounds and a pharmaceutical composition based on the said compounds, which can be used for treating or preventing cognitive disorders and/or neurodegenerative disorders.

10 cl, 1 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrrolopyrimidine and pyrrolopyridine of general formula (I), substituted with a cyclic amino group (II), or their pharmaceutically acceptable salts having CRF antagonist properties. In general formula the cyclic amino group has formula , in which the cyclic amino group is a 6-member saturated cyclic amine, the said cyclic amine is substituted with a group of formula -(CH2)mX; in which X is -CO2H, -CONH2,-P(=O)(OH)2 or -S(=O)2OH; Y is N or CH; m is an integer selected from 1, 2 and 3; R4 is hydrogen; R5 is hydrogen; R6 is C1-5alkyl; R7 and R8 are identical or different and independently represent hydrogen, C1-5alkyl, Ar is phenyl which is unsubstituted or substituted with one or more substitutes which are identical or different and are selected from a group consisting of halogen, C1-5alkyl, C1-5alkoxy, C1-5alkylthio, trifluoromethyl and trifluoromethoxy.

EFFECT: compounds can be used for therapeutic or preventive treatment of diseases where CRF is considered to be involved, such as depression, anxiety, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder, hypertension etc.

12 cl, 6 dwg, 1 tbl, 10 ex

FIELD: medicine.

SUBSTANCE: medicine for erectile dysfunction is a mixture of dry powder of panax ginseng roots, Codonopsis pilosula, Panax notoginseng, Astragalus membranaceus, powder of barrenwort herb or dry extract from barrenwort herb and additive agents with the following component ratio: 1:1:1:2:3:2 respectively. The medicine contains starch and magnesium stearate with the following ratio: 99:1 respectively and can be made in the form of capsules, pills, microcapsules, granules and powder.

EFFECT: medicine is low-toxic, high margins of safety and is safe when using intragastrically or perorally.

3 cl, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds with general formula I, in which R1 represents hydrogen or a group, which forms a biologically labile ester, R2 represents hydrogen, C1-C4-alkyl or C1-C4-hydroxyalkyl, and R3 represents C1-C4-alkyl; C1-C4-alkoxy-C1-C4-alkyl; C1-C4-hydroxyalkyl, which is optionally substituted with a second hydroxy group and all hydroxy groups of which are optionally esterified with C2-C4-alkanoyl or amino-acid residue; (C0-C4-alkyl)2amino-C1-C6-alkyl; C3-C7-cycloalkyl; C3-C7-cycloalkyl-C1-C4-alkyl; phenyl-C1-C4-alkyl, the phenyl group of which is optionally substituted 1-2 times with C1-C4-alkyl, C1-C4-alkoxy group and/or halogen; naphthyl-C1-C4-alkyl; C3-C6-oxoalkyl; phenylcarbonylmethyl, the phenyl group of which is optionally substituted 1-2 times with C1-C4-alkyl, C1-C4-alkoxy group and/or halogen, or 2-oxoazepanyl, or R2 and R3 together represent C4-C7-alkylene, methylene groups of which are optionally substituted 1-2 times with carbonyl, nitrogen, oxygen and/or sulphur and/or optionally substituted once with a hydroxy group, which is optionally esterified with C2-C4-alkanoyl or amino-acid residue; C1-C4-alkyl; C1-C4-hydroxyalkyl, the hydroxy group of which is optionally esterified with C2-C4-alkanoyl or amino-acid residue; phenyl or benzyl, and R4 represents hydrogen or a group, which forms a biologically labile ester, where R1 and R4 groups are independently chosen from C1-C4-alkyl; C1-C4-alkoxy-C1-C4-alkoxy-C1-C4-alkyl; C3-C7-cycloalkyl; C3-C7-cycloalkyl-C1-C4-alkyl; N,N-di-(C0-C4-alkyl)amino-C1-C6-alkyl; phenyl or phenyl-C1-C4-alkyl, optionally substituted 1 or 2 times in the phenyl ring with halogen, C1-C4-alkyl or C1-C4-alkoxy group or C1-C4-alkylene chain, bonded with two neighbouring carbon atoms; dioxolanylmethyl, optionally substituted in the dioxolane ring with C1-C4-alkyl; C1-C6-alkanoyloxy-C1-C4-alkyl, optionally substituted in the oxy-C1-C4-alkyl group with C1-C4-alkyl; 1-[[(C1-C4-alkyl)carbonyl]oxy]C1-C4-alkyl esters; 1-[[(C4-C7 cycloalkyloxy)carbonyl]oxy]C1-C4-alkyl esters, 2-oxo-1,3-dioxolan-4-yl-C1-C4-alkyl esters, which optionally contain a double bond in the dioxolane ring; 2-oxo-1,3-dioxolan-4-ylmethyl; and to physiologically compatible salts of acids with formula I and/or to physiologically compatible acid-additive salts of formula I compounds. The invention also relates to a pharmaceutical composition, to use of formula I compounds in paragraph 1, to a method of obtaining formula I compounds, as well as to compounds with general formula II.

EFFECT: obtaining new biologically active compounds, with inhibitory activity towards neutral endopeptidase, endothelin converting enzyme and soluble human endopeptidase.

20 cl, 80 ex, 9 tbl

FIELD: medicine.

SUBSTANCE: natural agent for male sexual function enhancement contains polyfleur farina (pollen load), honey, orchis (root), ginger plant (root), pumpkin seeds, 40% leuzea carthamoides tincture and swarming bee tincture in the following content: polyfleur farina (pollen load) 5.0; honey 2.0; orchis (root) 0.3; ginger plant (root) 0.5; pumpkin seeds (kernels) 1.0; leuzea carthamoides (40% tincture) 0.2; swarming bees (40% tincture) 0.2.

EFFECT: improved metabolism and tonus, stimulated immune system and considerable enhancement of sexual function.

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly to urology, and concerns therapy of patients suffering from chronic prostatitis. It is ensured by treatment of prostatitis including 4-5 physiotherapeutic courses every 6 months. Each course is preceded with blood test for testosterone concentration. If it is 12-18 nmol/l, preparation Nebido is prescribed in a dose 1000 mg. In case concentration exceeds 18 nmol/l, Nebido injection is omitted.

EFFECT: due to pulse introduction mode, therapy provides stimulation of androgen-dependent body functions in relative androgen deficiency and therefore improved clinical effectiveness of chronic prostatitis treatment with reduced drug body burden.

1 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, particularly to sexopathology, and method and drug for treating erectile dysfunction in men. Proposed is a drug with the following components, in mg: Kelp - 20.9182, active tadalafil - 5.44, mint - 2.0, aspartame - 0.8, glycerine - 2.0, FD&C Red 40 - 0.2, starch - 3.2, L-Menthol - 2.12, moisture - 2.432, polysorbate-80 - 0.6. The method is realised by introducing the said drug in the sublingual area in form of flavoured tablets.

EFFECT: overcoming asthenoneurotic component of erectile dysfunction, individual dosage of the drug and prolonged use without side effects.

2 tbl, 2 cl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention concerns pharmaceutics, particularly method of obtaining solid formulations containing vardenafil hydrochloride trihydrate. Method involves processing of formulation containing vardenafil hydrochloride or its hydrate (modification) by humid gas with relative humidity from 35 to 100% until vardenafil hydrochloride trihydrate is formed. In addition, invention concerns solid formulation of vardenafil hydrochloride trihydrate obtained by the claimed method.

EFFECT: improved stability of formulations obtained, obtaining solid formulations in unified replicable form.

4 cl, 8 dwg, 8 tbl, 12 ex

FIELD: medicine; sexual pathology.

SUBSTANCE: Sildenafil citrate dosed 12.5 mg or Tadalafil dosed 5 mg is introduced 1 hour prior to expected coitus and combined with Vicalin dosed 1 tablet. Method allows for lowered dosage of specified phosphodiesterase inhibitors type 5 in 2-4 times.

EFFECT: effective treatment without by-effects.

1 ex

FIELD: medicine; sexual pathology.

SUBSTANCE: prevention of cardiovascular by-effects induced by introduction of phosphodiesterase type 5 inhibitors for treatment of erectile dysfunction in men is ensured with introduction of one preparation from the specified group: Sildenafil citrate dosed 25-100 mg, or Vardenafil hydrochloride dosed 5-20 mg, or Tadalafil dosed 20 mg, combined with introduction of De-Nol dosed 1 tablet.

EFFECT: improved microcirculation due to higher synthesis of endogenous prostaglandins and prevented cardiovascular by-effects induced by introduction of specified preparations, improved erection in present category of patients.

1 ex

FIELD: medicine; sexual pathology.

SUBSTANCE: phosphodiesterase inhibitor type 5 that is Sildenafil citrate in unit-dose 12.5 mg is introduced. It is combined with antidepressant Maprolitine (Ludiomil) in unit-dose 5.0 mg daily, once a day. Course of treatment is 30 days.

EFFECT: effective treatment with preparations in smaller doses without by-effects.

1 ex

FIELD: chemistry.

SUBSTANCE: novel compounds are selected from group, consisting of: 4-(2-cyclopropyl-ethyl)-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-fluorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-(2-hydroxymethyl-cyclopropylmethyl)-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopentylmethyl-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-chlorine-4-(3-methyl- 4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-chlorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-(2-cyclopropyl-ethyl)-piperazine-1-carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-fluorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 2-fluorine-4-(3-methyl-4,10-dihudro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 2-fluorine-4-(3-methyl-4,10-dihydro-3H-2,3,4;9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-ethyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 2-chlorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 2-chlorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide and 4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-methoxy-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraazabenzo[f]azulene-9-carbonyl)-benzylamide. Invention also relates to pharmaceutical composition and to application of compounds of general formula 1.

EFFECT: obtaining novel biologically active compounds and based on them pharmaceutical composition, possessing antagonistic activity with respect to vasopressin receptors.

60 cl, 153 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (I) capable of bonding with S1P receptor (specifically EDG-6, preferably EDG-1 and EDG-6), its non-toxic water-insoluble salts or its methyl or ethyl ester.

EFFECT: obtaining compounds which can be used in preventing and/or treating graft rejection, graft-versus-host diseases, autoimmune diseases and allergic diseases.

11 cl, 66 ex

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