WO2014054975A2 - Composition pharmaceutique possédant une activité métabolique, anti-cataracte et rétinoprotectrice (et variantes) - Google Patents

Composition pharmaceutique possédant une activité métabolique, anti-cataracte et rétinoprotectrice (et variantes) Download PDF

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Publication number
WO2014054975A2
WO2014054975A2 PCT/RU2013/000806 RU2013000806W WO2014054975A2 WO 2014054975 A2 WO2014054975 A2 WO 2014054975A2 RU 2013000806 W RU2013000806 W RU 2013000806W WO 2014054975 A2 WO2014054975 A2 WO 2014054975A2
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WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
taurine
isotopes
sulfur
effect
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PCT/RU2013/000806
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English (en)
Russian (ru)
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WO2014054975A3 (fr
Inventor
Владимир Павлович ЛОБКО
Олег Олегович ТИХОНЕНКО
Анастасия Геннадьевна ЧЕЛЯЕВА
Original Assignee
Lobko Vladimir Pavlovich
Tikhonenko Oleg Olegovich
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Application filed by Lobko Vladimir Pavlovich, Tikhonenko Oleg Olegovich filed Critical Lobko Vladimir Pavlovich
Publication of WO2014054975A2 publication Critical patent/WO2014054975A2/fr
Publication of WO2014054975A3 publication Critical patent/WO2014054975A3/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/04—Sulfur, selenium or tellurium; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/26—Iron; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/30—Zinc; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/44—Elemental carbon, e.g. charcoal, carbon black
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/12—Ophthalmic agents for cataracts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism

Definitions

  • composition with metabolic, cataract, retinoprotective effect
  • the invention relates to medicine, namely to ophthalmology, and can be used as a metabolic agent,
  • Taurine - 2-aminoethanesulfonic acid improves energy processes, has metabolic, anti-cataract, retinoprotective and other actions.
  • an analogue located in retrobulbar space.
  • the disadvantage of an analogue is a small therapeutic effect.
  • Known eye drops (RF Patent 2295331, published March 20, 2007) have a reparative and antihypertensive effect based on a biogenic compound, which is one of the end products of the metabolism of sulfur-containing amino acids containing dextran and benzalkonium chloride, and contain taurine and additional cyanocobalamin as a biogenic compound.
  • the disadvantage of the analogue is the low rate of onset of the therapeutic effect in the treatment of corneal dystrophy, cataracts, corneal injury, damage to the lining of the eye, small therapeutic effect and not stability
  • the patent provides for the use of isotopes C, N, etc. for making isotopic labels in a drug.
  • the isotopes determine the dynamics of the distribution of the drug in the tissues of the body.
  • the disadvantage of the drug is the inability to use for the treatment of eye diseases.
  • a nutritional supplement can be used to enrich a variety of foods.
  • the disadvantage of a dietary supplement is the inability to use for the treatment of eye diseases.
  • taurine containing a nutritional vitamin-mineral supplement (RF Patent 2335926, published October 20, 2008), including -acetyl-L- glutamic acid, pyridoxine hydrochloride (vitamin B 6 ), glycine
  • aminoacetic acid aminoacetic acid
  • zinc acetate dihydrate or zinc citrate riboxin
  • nicotinamide vitamin PP (VZ)
  • taurine taurine
  • succinic acid HOOC-CH 2 -CH 2 - COOH
  • the disadvantage of a dietary supplement is the inability to use for the treatment of eye diseases.
  • the prototype of the two variants of the invention is a pharmaceutical composition (http://medi.ru DOC / x0905.htm) having a metabolic,
  • Taurine is a sulfur-containing amino acid formed in the body during the conversion of cysteine. Stimulates repair processes and
  • the content of taurine is 4%. It is used in ophthalmology for: dystrophic lesions of the retina of the eye; hereditary
  • the pharmaceutical composition contributes to the normalization of the functions of cell membranes, activation of energy and metabolic processes, preservation of the electrolyte composition of the cytoplasm, etc. It has a metabolic effect.
  • the disadvantage of the prototype is the relatively low speed of the onset of the therapeutic effect in the treatment of corneal dystrophy, cataracts, corneal injury, damage to the lining of the eye, small therapeutic effect and not stability during the expiration date.
  • shelf life the period during which the pharmaceutical composition retains its properties in a measure that ensures its use according to
  • Anti-cataract activity - activity aimed at protecting the lens proteins of the eye (lens protection from clouding, progression
  • Retinoprotective action an action aimed at protecting the retina.
  • Metabolic action - an action aimed at metabolic processes in the eye cell.
  • Metabolic agent - a means of regulating the metabolism in the body.
  • Electroretinography is a graphic recording of bioelectric potentials that occur in the retina of the eye when exposed to light;
  • Retinopathy is a non-inflammatory lesion of the retina of the eyeball. The main reason is vascular disorders that lead to retinal blood supply disorder. Retinopathy often manifests itself as a complication of hypertension, diabetes mellitus and other systemic diseases.
  • Retinal progressive atrophy is a term used to describe a number of hereditary neuroretinal degenerations: generalized
  • GPAS progressive retinal atrophy
  • CPAS central progressive retinal atrophy
  • the pharmaceutical composition having a metabolic, anti-cataract, retinoprotective effect contains taurine and differs from the prototype in that it additionally contains mineral substances in the following ratio of components in mg / l:
  • the problem is solved due to the fact that the pharmaceutical composition having a metabolic, anti-cataract, retinoprotective effect contains taurine and differs from the prototype in that it additionally contains mineral substances in the following ratio of components in mg / l:
  • the pharmaceutical composition is made in such a way that it contains 13 C carbon isotopes, and the ratio of 13 C carbon isotopes to the total amount of carbon in the pharmaceutical composition is from 0.003 to and contains sulfur isotopes S, and the ratio of the amount of sulfur isotopes 34 c S to the total amount of sulfur in the pharmaceutical composition is from 0.0001 to 0.1 13.
  • the pharmaceutical composition is made in the form of a dosage form - eye drops (made in the form of eye drops).
  • the pharmaceutical composition can be performed with a pH of from 7.0 to 7.9.
  • the active substance is taurine.
  • the taurine molecule contains an acidic sulfo group SO 3 H and a basic amino group NH 2 .
  • the kinematic viscosity of the pharmaceutical composition in the form of eye drops is from 1.01 to 1.23 mm / s and is determined, first of all, by the content of the active substance and minerals in water.
  • the kinematic viscosity of the pharmaceutical composition is determined using a capillary viscometer.
  • the claimed pharmaceutical formulations are used, like the prototype, for the following eye diseases: corneal dystrophy; cataract (senile, diabetic, traumatic, radiation); corneal injury (as
  • a pharmaceutically acceptable solvent in addition to the active substance and minerals, a pharmaceutically acceptable solvent can be used.
  • a pharmaceutically acceptable excipient or pharmaceutically acceptable excipients may be used in the pharmaceutical composition.
  • a pharmaceutically acceptable excipient may not be used in the pharmaceutical composition.
  • a pharmaceutically acceptable solvent can be used water (distilled water, water for injection), as well as another solvent.
  • methyl parahydroxybenzoate (nipagin) or another substance may be used.
  • a pharmaceutically acceptable excipient is usually a preservative and / or antiseptic.
  • the substance actively inhibits the growth of gram-positive bacteria, gram-negative bacteria.
  • the active substance taurine and minerals in a pharmaceutically acceptable solvent, in particular in water.
  • the active substance taurine and minerals are selected from the above ranges, and the rest (water) is selected.
  • cardiostimulating effect while maintaining the duration of action
  • up to 95% ethyl alcohol is introduced into the drug.
  • Alcohol due to osmotic phenomena causes pain and local negative reaction, which accelerates the effect of the drug.
  • polyvinylpyrrolidone and sorbic acid These components increase the antitumor activity of the active principle.
  • the concentration of the active substance in the pharmaceutical agent due to the introduction of mineral substances into the pharmaceutical composition.
  • Trace elements iron, copper, manganese, zinc, cobalt, iodine, fluorine, chromium, molybdenum, vanadium, nickel, strontium, silicon, selenium are recognized as essential for human and animal life.
  • Macronutrients regulate water-salt metabolism, maintain the osmotic pressure in cells and intercellular fluids, which is necessary for the movement of nutrients and drugs between them. Blood formation processes occur with the participation of iron, copper, manganese, calcium and other mineral substances (elements).
  • Minerals (trace elements) activate the action of enzymes, hormones, participate in all types of metabolism.
  • Mineral substances in solution (in particular, in pharmaceutical composition) are contained in pharmaceutically acceptable salts, for example, succinates, chlorides, carbonates or sulfates, as well as in various pharmaceutically acceptable complex compounds.
  • Enzyme inactivation occurs through the interaction of metal ions with sulfhydryl groups of enzymes.
  • Metals have a pronounced local effect on the mucous membranes. At the concentrations of mineral substances considered in the application, the local action of these substances may be astringent or irritating.
  • FIG. 1 Presents 13C-NMR spectrum of the pharmaceutical composition.
  • FIG. 2 Presents 1H-NMR spectrum of the pharmaceutical composition.
  • FIG. 3 Presents a fragment of 1H-NMR spectrum of the pharmaceutical composition.
  • FIG. 4 presents a chromatogram of the pharmaceutical composition on a column with sorbent C 18. Yu
  • FIG. 5 shows the left side of the chromatogram of the pharmaceutical composition on a column with sorbent C 18.
  • FIG. 6 shows the right side of the chromatogram of the pharmaceutical composition on a column with sorbent C 18.
  • FIG. 7 shows a chromatogram of the pharmaceutical composition on a column with sorbent C 18.
  • FIG. 8 shows the left side of the chromatogram of the pharmaceutical composition, on a column with sorbent C 18.
  • FIG. 9 shows the right side of the chromatogram of the pharmaceutical composition on a column with sorbent C 18.
  • Figure 10 presents a graph with the results of studies of the claimed pharmaceutical formulations.
  • Figure 1 1 presents a diagram of a cavitation reactor for isotopic enrichment of various mixtures.
  • Fig presents a diagram of the installation for isotope enrichment.
  • Example 1 a method of introducing minerals into water.
  • Example 2 - a method of obtaining pharmaceutical compositions and verification of stability.
  • Example 3 tests for general toxicity.
  • Example 4 - illustrate the effectiveness of the claimed pharmaceutical compositions having metabolic, anticataract,
  • Example 1 The introduction of minerals into the solution (in water) was carried out according to the method described in the source / Guide to methods for monitoring the quality and safety of biologically active food additives. - M.: Federal Center State Sanitary and Epidemiological Supervision Ministry of Health of Russia, 2004, - 240s /. There are other ways to introduce minerals into the solution. Solutions were prepared from pure metals using pharmaceutically acceptable solvents to ensure storage stability of the solutions.
  • the concentration of metals in solutions was controlled by the atomic absorption method for determining the contents of sodium, potassium, calcium, magnesium, iron, manganese, copper, zinc, lead, cadmium, cobolt, nickel, and chromium. Clause 1.3.2.1 of the source / Guide to quality and safety control methods
  • compositions containing taurine with minerals were studied: potassium, sodium, calcium, manganese, copper, cobalt, chromium, and molybdenum.
  • concentration of these metals in solutions was provided in the following ranges, mg / l:
  • Example 2 For example, we describe the receipt of a pharmaceutical composition containing taurine and minerals, mg / l: taurine - 40 '10 3 ;
  • the control showed the qualitative performance of the pharmaceutical composition.
  • FIG. 1-9 illustrate studies of only one of the above pharmaceutical compositions with taurine and minerals.
  • FIG. 1 Presents 13 C-NMR spectrum of the pharmaceutical composition: 13 C NMR (360 MHz, D20): 46.63; 34.60.
  • FIG. 2 Presents 1H-NMR spectrum of the pharmaceutical composition.
  • FIG. 4 shows a chromatogram of the pharmaceutical composition, on a column with sorbent C 18, with detection at 220 nm.
  • FIG. 5 shows the left side of the chromatogram of the pharmaceutical composition, on a column with sorbent C 18, with a mass selective detector. A peak with a retention time of 2.6 minutes is highlighted. 126.7 is the signal of the desired ion. 251.8; 376.2; 501.3; 626.2; 626.2; 751, 1 - signals of dimer, trimmer, tetramer, etc. the desired ion.
  • FIG. 6 shows the right side of this chromatogram of the pharmaceutical composition.
  • FIG. 7 shows a chromatogram of a pharmaceutical composition, on a column with sorbent C 18, with detection at 220 nm.
  • FIG. Figure 8 shows the left side of the chromatogram of the pharmaceutical composition, on a column with a sorbent C 18, with a mass selective detector. A peak with a retention time of 2.6 minutes is highlighted. 126.7 - signal of the desired ion, 251 - signal of the dimer of the desired ion.
  • FIG. 9 shows the right side of this chromatogram of the pharmaceutical composition.
  • the indicator “real component of relative dielectric constant” was a control, a kind of criterion for the applicability of the pharmaceutical composition.
  • Example 3 Tests for general toxicity were performed by administering pharmaceutical compositions based on taurine and minerals to rats.
  • LD 50 is up to 1000 mg / kg when administered intraperitoneally. With intramuscular injection, LD 50 is up to 3000 mg / kg, which allows the claimed compounds to be classified as non-toxic substances. With long-term use of pharmaceutical compositions based on taurine and minerals in rats, no changes were found in the organs and tissues of the body (were insignificant).
  • Example 4 Evaluation of the effectiveness of the claimed pharmaceutical compositions in animals with progressive retinal atrophy.
  • Evaluation of the effectiveness of the claimed pharmaceutical compositions was carried out in comparative trials with the drug taufon.
  • the comparison criterion was the characteristics of a- and ⁇ -waves of electroretinograms in animals before and after treatment.
  • Electroretinography was carried out according to the method developed by scientists of the Moscow State Academy of Veterinary Medicine and
  • Table 10 presents the comparative characteristics of electroretinograms in healthy and sick dogs at various stages
  • the amplitudes of the ⁇ 1 wave, the a2 wave, the ⁇ wave, and the p2 wave were used as indicators.
  • electroretinograms in healthy and sick cats and rats at different stages of the disease look.
  • Table 1 1 presents the change in the amplitude of the p2 wave
  • FIG. 10 also shows the regions through which the curves of the dependence of the amplitude of the p2 wave on time pass when using
  • the pharmaceutical composition of Ns 9 is equal in action to the action
  • the pharmaceutical composition N ° 14 in its effect is equal to the action of the pharmaceutical composition Ns 13. Graphs showing the effect of these compounds pass through the region 38.
  • the pharmaceutical composition of Ns 19 in its effect is equal to the action of the pharmaceutical composition of Ns 18.
  • Graphs showing the effect of these compounds pass through region 38 closer to the lower boundary of the region.
  • the pharmaceutical composition Ns 24 in its effect is equal to the action of the pharmaceutical composition ⁇ ° 23. Graphs showing the effect of these compounds pass through the area 38 closer to the upper boundary.
  • the pharmaceutical composition of Ns 29 in its effect is equal to the action of the pharmaceutical composition of Ns 28.
  • Graphs depicting the effect of these compounds pass through region 39.
  • the pharmaceutical composition of Ns 34 in its effect is equal to the effect of the pharmaceutical composition J4 o 33.
  • Graphs showing the effect of these compounds pass through region 41 closer to the lower boundary of the region.
  • the pharmaceutical composition of Ns 39 in its effect is equal to the action of the pharmaceutical composition of Ns 38.
  • Graphs showing the effect of these compounds pass through region 41 closer to the upper boundary.
  • the pharmaceutical composition of Ns 44 in its effect is equal to the action of the pharmaceutical composition of Ns 43. Graphs depicting the effect of these compounds pass through region 42.
  • the pharmaceutical compositions N ° N ° 4, 9, 14, 19, 24, 29, 34, 39 and 44 are not practical to use in practice due to the absence of differences in
  • the pharmaceutical composition ⁇ ° 5 in its effect is inferior (by about 3 - 5%) to the action of the pharmaceutical composition N ° 3 and the action of taurine
  • the pharmaceutical composition of ⁇ ° 10 is inferior in its effect (by about 3
  • the pharmaceutical composition N ° 15 is inferior in its effect (by about 3
  • the pharmaceutical composition is N 0 . 20 inferior in effect (by about 5
  • the pharmaceutical composition of Ne 25 is inferior in its effect (by about 5
  • the pharmaceutical composition N ° 35 is inferior in its effect (by about 10
  • the pharmaceutical composition N ° 40 is inferior in its effect (by about 10
  • compositions N ° N ° 5, 10, 15, 20, 25, 30, 35, 40, 45 in practice, it is not advisable to use, since their effect is worse than the action of taufon with the appropriate concentration.
  • the pharmaceutical composition is designed in such a way that it contains carbon isotopes 13 C, and the ratio of the number of carbon isotopes 13 C to the total amount of carbon in the pharmaceutical composition is from 0.003 to 0.75;
  • the ratio of the amount of 34 S sulfur isotopes to the total amount of sulfur in the pharmaceutical composition is from 0.0001 to 0.113.
  • the obtained results of animal studies can be used in the treatment of corneal dystrophy, cataracts, corneal trauma, damage to the lining of the eye.
  • the mechanisms for treating eye diseases in animals and humans are similar.
  • composition of mineral substances in the pharmaceutical compositions described above was limited by the list of mineral substances (macroelements and
  • the Guide describes a method for introducing mineral substances into a solution, as well as methods for precisely controlling the amount of mineral substances in solutions.
  • any may be added or any of the following may be added (with the exception of the minerals already indicated in the composition), mg / l:
  • composition A can be performed as follows:
  • composition can be performed as follows:
  • composition B The second composition (composition B) can be performed as follows:
  • the pharmaceutical composition is designed in such a way that it contains carbon isotopes 13 C, and the ratio of the number of carbon isotopes 13 C to the total the amount of carbon in the pharmaceutical composition is from 0.003 to 0.75;
  • the ratio of the amount of 34 S sulfur isotopes to the total amount of sulfur in the pharmaceutical composition is from 0.0001 to 0.1 13.
  • composition can be performed as follows:
  • the pharmaceutical composition is designed in such a way that it contains carbon isotopes lj C, and the ratio of the number of carbon isotopes 13 C to the total amount of carbon in the pharmaceutical composition is from 0.003 to 0.75;
  • the ratio of the amount of 34 S sulfur isotopes to the total amount of sulfur in the pharmaceutical composition is from 0.0001 to 0.1 13.
  • Carbon isotopes 13 C are not toxic. Experiments show that feeding rats with food and instilling eyes with a taurine compound enriched with 75% carbon
  • compositions enriched in carbon C isotopes have increased stability, they are non-toxic and, in addition, have an increased metabolic, anti-cataract, retinoprotective effect compared to a pharmaceutical composition in which there are no carbon isotopes
  • the reactor was manufactured according to the methodology given in the source / R.F. Ganiev, V.I. Kormilitsyn, L.I. Ukrainsky. Wave cooking technology
  • Figure 1 1 shows a diagram of a cavitation reactor for isotope enrichment of various mixtures, in particular, hydrocarbon reagents for the production of taurine enriched in carbon isotopes C.
  • the reactor is located in the installation, which contains a pump 6NK-6x1, providing a maximum flow rate of 90 m 3 / hour, a pressure of 125 m with an electric motor power of 75 kW, a rotational speed of an electric motor rotor and a pump wheel of 2950 rpm. Additionally, the installation contains tanks for reagents and measuring instruments.
  • the cavitation reactor 1 (see figure 1 1) is made in the form of a flat Laval nozzle with cavitation bodies 2-9 in the channel 10.
  • Fig presents a cross section of a cavitation reactor.
  • the reactor channel in the area of cavitation bodies is divided into several channels.
  • cavitation bodies 5 and 6 divide the channel into smaller channels 13, 14 and 15. Outside, the channel is limited by walls 16 and 17, as well as two covers 1 1 and 12.
  • channels 24 and 25 are made for supplying carbon dioxide and nitrogen to the cavitation zones.
  • Installation works as follows.
  • the hydrocarbon reagent from the tank 28 using the pump 26 is pumped through the reactor 27 and goes back to capacity 28.
  • the pressure drop across the reactor is controlled by pressure gauges 29 and 30.
  • the temperature of the reagent is controlled by a thermometer 31.
  • the reagent is heated in the tank by a heater 32.
  • the hydrocarbon reagent moves along the cavitator channel in direction 18.
  • the flow is divided into several flows. Beyond the cavitation bodies, cavitation areas arise.
  • cavitation 2 3, and 4 are cavitation zones 20, 21, 22, and 23.
  • cavitation 2 Upon entering the cavitation region, the reagent “boils”, cavitation bubbles appear, and cavitation cavities exit the cavitation region the bubbles collapse.
  • an increase in pressure to several thousand atmospheres and an increase in temperature to a thousand degrees are observed
  • the gas-vapor mixture obtained in the reactor together with the liquid reagent enters the tank 28.
  • the gas-vapor mixture is passed through a pipe 33 to a separator with a porous partition, where the gas-vapor mixtures with 13 C and
  • the amount of carbon C isotopes was controlled by high resolution mass spectroscopy.
  • the reagent was enriched with the 13 C carbon isotope to 75%.
  • compositions were obtained containing taurine with a carbon content of 13 C from 0.3% to 75% of the total carbon in the pharmaceutical composition.
  • the above cavitation reactor During reactor operation, the reagent moves along the cavitator channel in direction 18. When flowing around cavitation bodies, the flow splits into multiple threads. Beyond the cavitation bodies, cavitation areas arise. At the entrance to the cavitation area, the reagent “boils”, cavitation bubbles appear, when leaving the cavitation area, cavitation bubbles collapse. In the experiment, nitrogen was supplied through the channels 24 and 25 in such a way that the gas entered the cavitation zones.
  • the vapor-gas mixture obtained in the reactor together with the reagent enters the tank 28.
  • the gas-vapor mixture is fed through a pipe 33 to a separator with a porous partition, where the gas-vapor mixtures with 14 N and ⁇ 5 ⁇ are separated.
  • the gas-vapor mixture obtained in the reactor together with the reagent enters the tank 28.
  • the gas-vapor mixture is fed through a pipe 33 to a separator with a porous baffle, where the gas-vapor mixtures with S and S are separated.
  • the reagent was enriched in sulfur isotope 33 S OT 0.01% to 3.7%.
  • the gas-vapor mixture obtained in the reactor together with the reagent enters the tank 28.
  • the gas-vapor mixture is passed through a pipe 33 to a separator with a porous baffle, where the gas-vapor mixtures with 32 S and j4 S are separated.
  • the reagent was enriched in the 34 S sulfur isotope from 0.01% to 1 1.3%.
  • compositions were enriched and tested in practice, enriched in 13 C isotopes (sometimes it is written 13C), and / or 15 N (sometimes it is written 15N), and / or 33 S (sometimes it is written 33S), and / or j4 S (sometimes it is written 34S).
  • formulations were selected whose action is 3 to 5% or more higher than the action of taurine or compounds with the corresponding taurine content (from 1 10 3 to 160 10 mg / l).
  • these selected pharmaceutical formulations can be written as follows:
  • the pharmaceutical composition is designed in such a way that it contains carbon isotopes 13 C, and the ratio of the number of carbon isotopes 13 C to the total amount of carbon in the pharmaceutical composition is from 0.003 to 0.75.
  • the pharmaceutical composition is designed in such a way that it contains nitrogen isotopes of 5 5 ⁇ , and the ratio of the amount of nitrogen isotopes ⁇ 5 ⁇ to the total amount of nitrogen in the pharmaceutical composition is from 0.0001 to 0.1375.
  • sulfur isotopes S and the ratio of the amount of sulfur isotopes J S to the total amount of sulfur in the pharmaceutical composition is from 0.0001 to 0. 037.
  • the pharmaceutical composition is designed in such a way that it contains sulfur isotopes j4 S, and the ratio of the number of sulfur isotopes 34 S to the total amount of sulfur in the pharmaceutical composition is from 0.0001 to 0.1 13.
  • the pharmaceutical composition is designed in such a way that it contains carbon isotopes 13 C, and the ratio of the number of carbon isotopes 13 C to the total amount of carbon in the pharmaceutical composition is from 0.003 to 0.75;
  • the ratio of the amount of 15 N nitrogen isotopes to the total amount of nitrogen in the pharmaceutical composition is from 0.0001 to 0.1375.
  • the pharmaceutical composition is designed in such a way that it contains carbon isotopes of 1 3 C, and the ratio of the number of carbon isotopes of 13 C to the total amount of carbon in the pharmaceutical composition is from 0.003 to 0.75;
  • the ratio of the amount of 3j S sulfur isotopes to the total amount of sulfur in the pharmaceutical composition is from 0.0001 to O. 037.
  • the pharmaceutical composition is designed in such a way that it contains carbon isotopes 13 C, and the ratio of the number of carbon isotopes 13 C to the total amount of carbon in the pharmaceutical composition is from 0.003 to 0.75;
  • the ratio of the amount of 34 S sulfur isotopes to the total amount of sulfur in the pharmaceutical composition is from 0.0001 to 0.1 13.
  • the pharmaceutical composition is designed in such a way that it contains
  • the ratio of the number of nitrogen isotopes 15 N to the total amount of nitrogen in the pharmaceutical composition is from 0.0001 to 0.1375;
  • the ratio of the number of sulfur isotopes J S to the total amount of sulfur in the pharmaceutical composition is from 0.0001 to O. 037.
  • the pharmaceutical composition is designed in such a way that it contains nitrogen isotopes 15 N, and the ratio of the number of nitrogen isotopes 15 N to the total amount of nitrogen in the pharmaceutical composition is from 0.0001 to 0.1375;
  • the ratio of the number of sulfur isotopes 34 S to the total amount of sulfur in the pharmaceutical composition is from 0.0001 to 0.1 13.
  • the pharmaceutical composition is designed in such a way that it contains 34 S sulfur isotopes, and the ratio of the amount of 34 S sulfur isotopes to the total amount of sulfur in the pharmaceutical composition is from 0.0001 to 0.1 13; and contains sulfur isotopes JJ S, and the ratio of the amount of sulfur isotopes S to the total amount of sulfur in the pharmaceutical composition is from 0.0001 to 0. 037.
  • the pharmaceutical composition is designed in such a way that it contains carbon isotopes
  • the ratio of the amount of nitrogen isotopes ⁇ 5 ⁇ to the total amount of nitrogen in the pharmaceutical composition is from 0.0001 to 0.1375;
  • the ratio of the amount of 33 S sulfur isotopes to the total amount of sulfur in the pharmaceutical composition is from 0.0001 to 0. 037.
  • the pharmaceutical composition is designed in such a way that it contains nitrogen isotopes ⁇ 5 ⁇ , and the ratio of the number of nitrogen isotopes ⁇ 5 ⁇ to the total amount of nitrogen in the pharmaceutical composition is from 0.0001 to 0.1375; and contains 33 S sulfur isotopes, and the ratio of the amount of 33 S sulfur isotopes to the total amount of sulfur in the pharmaceutical composition is from 0.0001 to O. 037;
  • the ratio of the amount of sulfur isotopes 34 S to the total amount of sulfur in the pharmaceutical composition is from 0.0001 to 0.1 13.
  • the pharmaceutical composition is designed in such a way that it contains carbon isotopes 13 C, and the ratio of the number of carbon isotopes 13 C to the total amount of carbon in the pharmaceutical composition is from 0.003 to 0.75;
  • the ratio of the number of sulfur isotopes 3j S to the total amount of sulfur in the pharmaceutical composition is from 0.0001 to O. 037;
  • the ratio of the amount of 34 S sulfur isotopes to the total amount of sulfur in the pharmaceutical composition is from 0.0001 to 0.1 13.
  • the pharmaceutical composition is designed in such a way that it contains carbon isotopes 13 C, and the ratio of the number of carbon isotopes 13 C to the total the amount of carbon in the pharmaceutical composition is from 0.003 to 0.75;
  • the ratio of the number of nitrogen isotopes 15 N to the total amount of nitrogen in the pharmaceutical composition is from 0.0001 to 0.1375;
  • the ratio of the amount of 34 S sulfur isotopes to the total amount of sulfur in the pharmaceutical composition is from 0.0001 to 0.1 13.
  • the pharmaceutical composition is designed so that it contains the carbon isotopes 13 C and ratio of carbon isotopes 13 C to the total amount of carbon in the pharmaceutical composition amounts from 0.003 to 0.75;
  • the ratio of the number of sulfur isotopes S to the total amount of sulfur in the pharmaceutical composition is from 0.0001 to O. 037;
  • the ratio of the amount of 34 S sulfur isotopes to the total amount of sulfur in the pharmaceutical composition is from 0.0001 to 0.1 13.
  • the pharmaceutical composition is designed in such a way that it contains carbon isotopes 13 C, and the ratio of the number of carbon isotopes 13 C to the total amount of carbon in the pharmaceutical composition is from 0.003 to 0.75;
  • the ratio of the number of nitrogen isotopes 15 N to the total amount of nitrogen in the pharmaceutical composition is from 0.0001 to 0.1375;
  • the ratio of the amount of 33 S sulfur isotopes to the total amount of sulfur in the pharmaceutical composition is from 0.0001 to O. 037;
  • the ratio of the amount of 34 S sulfur isotopes to the total amount of sulfur in the pharmaceutical composition is from 0.0001 to 0.113.
  • compositions with a content of taurine 40 '10 mg / L pass through the regions 37, 38 and 39. Moreover, the curves describing the effect of 4% taufona pass through the region 37.
  • compositions with a content of taurine 160 10 mg / l pass through areas 40, 41 and 42. Moreover, the curves describing the effect of taurine with
  • the pharmaceutical composition is designed in such a way that it contains carbon isotopes 13 C, and the ratio of the number of carbon isotopes 13 C to the total amount of carbon in the pharmaceutical composition is from 0.003 to 0.75;
  • the ratio of the amount of 34 S sulfur isotopes to the total amount of sulfur in the pharmaceutical composition is from 0.0001 to 0.1 13.
  • carbon isotopes 13 C (the ratio of the number of carbon isotopes 13 C to the total amount of carbon in the pharmaceutical composition is 0.003); 34 S sulfur isotopes (ratio of 34 S sulfur isotopes to total
  • the amount of sulfur in the pharmaceutical composition is 0.0001).
  • carbon 13 isotopes (the ratio of the number of carbon C isotopes to the total amount of carbon in the pharmaceutical composition is 0.75);
  • the amount of sulfur in the pharmaceutical composition is 0.1 0.1).
  • carbon isotopes 13 C (the ratio of the number of carbon isotopes 13 C to the total amount of carbon in the pharmaceutical composition is 0.003); 34 S sulfur isotopes (ratio of 34 S sulfur isotopes to total
  • the amount of sulfur in the pharmaceutical composition is 0.0001).
  • carbon isotopes 13 C (the ratio of the number of carbon isotopes 13 C to the total amount of carbon in the pharmaceutical composition is 0.75);
  • the amount of sulfur in the pharmaceutical composition is 0.1 0.1).
  • carbon isotopes 13 C (the ratio of the number of carbon isotopes 13 C to the total amount of carbon in the pharmaceutical composition is 0.003); 34 S sulfur isotopes (ratio of 34 S sulfur isotopes to total
  • the amount of sulfur in the pharmaceutical composition is 0.0001).
  • carbon isotopes 13 C (the ratio of the number of carbon isotopes 13 C to the total amount of carbon in the pharmaceutical composition is 0.75);
  • 34 S sulfur isotopes (the ratio of 34 S sulfur isotopes to the total amount of sulfur in the pharmaceutical composition is 0.1 13).

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Inorganic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Ophthalmology & Optometry (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

L'invention appartient au domaine de la médecine et notamment de l'ophtalmologie. L'objectif visé par la présente invention est la création d'une composition pharmaceutique efficace possédant une action métabolique, anti-cataracte, rétinoprotectrice grâce au fait que la composition pharmaceutique contient de la taurine et, de plus, des substances minérales ainsi que les isotopes 13C, 34S. La mise en oeuvre des compositions pharmaceutiques de l'invention permet d'assurer un meilleur effet thérapeutique et d'accélérer la survenance de l'effet thérapeutique sans augmenter la concentration de taurine, et d'augmenter la stabilité de la composition pharmaceutique contenant la taurine pendant toute la durée de vie.
PCT/RU2013/000806 2012-10-01 2013-09-17 Composition pharmaceutique possédant une activité métabolique, anti-cataracte et rétinoprotectrice (et variantes) WO2014054975A2 (fr)

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EA201201218 2012-10-01
EA201201218A EA020361B1 (ru) 2012-10-01 2012-10-01 Фармацевтический состав, содержащий магний, железо, цинк и обладающий метаболическим, противокатарактным, ретинопротекторным действием (варианты)

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EA008591B1 (ru) * 2002-12-31 2007-06-29 Пфайзер Продактс Инк. Производные 3-(3,5-диоксо-4,5-дигидро-3h-(1,2,4)триазин-2-ил)бензамида в качестве ингибиторов p2xдля лечения воспалительных заболеваний

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EA008591B1 (ru) * 2002-12-31 2007-06-29 Пфайзер Продактс Инк. Производные 3-(3,5-диоксо-4,5-дигидро-3h-(1,2,4)триазин-2-ил)бензамида в качестве ингибиторов p2xдля лечения воспалительных заболеваний

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
CHELIAEVA A. G. MINERALNYE VESHCHESTVA, [Online] 24 September 2011, Retrieved from the Internet: <URL:http:icfond.ra/servises/item/minelal- vechestva?category id= 1> *
DATABASE PMID [Online] Database accession no. 19427840 & CHEN K. ET AL.: 'Taurine protects transtormed rat retinal ganglion cells from hypoxia-induced apoptosis by preventing mitochondrial dysfunction.' BRAIN RES. vol. 1279, 07 July 2009, pages 131 - 8 *
LOBKO V. P. ET AL.: 'Nano-kavitatsionnaya tekhnologia obogashchenia veshchestv izotopom ugleroda', [Online] 22 September 2011, Retrieved from the Internet: <URL:http:icfond.ra/servises/item/nano-cavi tac?category_id=l>> *
'RLS-2006' REGISTR LEKARSTVENNYKH SREDSTV ROSSII. ENTSIKLOPEDIA LEKARSTV vol. 14, 2005, VYPUSK. MOSKVA, page 769 *

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