Pharmaceutical composition for treating eye diseases as a result of microcirculation disorders and/or inflammatory processes

FIELD: medicine, ophthalmology, chemico-pharmaceutical industry.

SUBSTANCE: the suggested pharmaceutical composition is indicated for local application and contains an inhibitor angiotensin converting enzyme as an active substance and target additions, moreover, the content of active substance corresponds to about 1-20 mg/ml. The composition suggested could be designed as eye drops, spay, gels, solution for local injections. As target additions one should apply water that contains a buffer agent, an isotonic mixtures, a conservant and a prolongator. Additionally, this composition contains preparations chosen out of the following groups: antibiotics, macro- and microelements, vitamins, adrenoblocking agents. The innovation provides anti-ischemic action, improves reparative processes and accelerates the processes of healing.

EFFECT: higher efficiency.

3 cl, 7 ex

 

The invention relates to pharmaceutical industry and relates to pharmaceutical compositions for topical application in the treatment and prevention of eye pathologies associated with impaired microcirculation and/or inflammatory processes.

The circulation is an important pathogenetic link of diseases such as degenerative diseases of the retina and optic nerve, diabetic retinopathy, age-related retinal degeneration, burn ischemia conjunctiva, occlusion of retinal vessels, optic neuropathy, and other inflammation include domestic, industrial and military trauma (mechanical, chemical, thermal, radiation, caused by exposure to laser), keratitis various etiologies, uveitis and other

At the present time in the world practice for the treatment of such pathologies of the eye, apply the following approaches. Microcirculation disorders and, in particular, in dystrophic used vasodilator and antispasmodic drugs, fibrinolitiki, anticoagulants, biogenic stimulants, and vitamins [1-4]. In the treatment of diabetic retinopathy main method of treatment is laser photocoagulation of retinal vessels and surgical treatment. In inflammatory processes typically used nonspecific anti-inflammatory drugs the ATA (antibiotics, corticosteroids), preparations based inhibitors of proteinases, enzymes, immunomodulators, anti-infective means biogenic stimulators of reparative processes, antioxidants, angioprotectors [5-8]. In the case of tissue necrosis have to resort to surgery. However, the currently adopted methods of treatment are not effective enough, and sometimes have negative consequences. Corneal ulcers are difficult to treat, often formed by coarse opaque thorn, effective specific drugs for local application that allows you to arrest vascular spasm of the conjunctiva and limbus to avoid ischemia of the tissues of the eye and subsequent necrosis, on the pharmaceutical market there. In addition, there are no means capable of simultaneously affect the repair of tissues and restore disturbed microcirculation. The advantage of the proposed pharmaceutical composition is its unique complex of anti-ulcer, anti-ischemic and anti-oxidant effects.

One of the pathogenetic links uniting the above diseases is the imbalance of the components of General and local (in the eye) the renin-angiotensinogen systems (RAS). The renin-angiotensin system is one of the most important regulatory systems organisms is A. Central regulatory element of the RACES is angiotensinase enzyme (ACE)inhibitors. ACE is zincability peptidase that catalyzes the hydrolytic cleavage of dipeptides from the carboxyl end of a number of physiologically active Oligopeptide substrates, in particular of angiotensin I and bradykinin. In the result of limited proteolysis by ACE, angiotensin I is converted into a powerful vasoconstrictor angiotensin II, causing vasospasm, and vasodilator bradykinin, which causes vasodilatation, in contrast, is inactivated. ACE inhibitors block the activity of the enzyme and preventing thereby the formation of angiotensin II and degradation of bradykinin. Thus, ACE inhibitors, create the conditions for local tissue accumulation of bradykinin, which in turn stimulates the release of nitric oxide (NO) and prostaglandins. This mechanism is of great importance for the smooth muscle cells of the vascular wall due to the fact that NO can inhibit mitogenic and proliferation of these cells [9, 10]. Moreover, prostaglandins and NO possess vasodilator, so it can improve the function of large vessels and tissue perfusion. ACE inhibitors along with the ability to improve endothelial function, inhibit the growth and proliferation of smooth muscle cells have the ability to brake the th migration and function of macrophages, to reduce thrombotic activity by preventing platelet aggregation and amplification of endogenous fibrinolysis [11].

Currently, the ACE inhibitors are widely used orally or intravenously for the treatment of hypertension and cardiovascular disease [5]. In the literature there is information about the positive effect by oral administration of ACE inhibitors in atherosclerosis [12] and insulin-dependent diabetes mellitus [13].

Current data suggest the existence, in addition to humoral generalized RACES, systems local tissue factors in various organs and many physiological functions RACES connected with its local action - paracrine, autocrine and intracrine. To date, tissue structures and liquid environments eyes found many of the components of RACES that can play a significant role in the pathogenesis of various diseases of the eye [14]. Currently there is information about the positive effect of oral administration of ACE inhibitors senile degeneration of the retina [15] and diabetic retinopathy [16]. There are indications that local administration of ACE inhibitors to reduce intraocular pressure in glaucoma [17] and the treatment of corneal ulcers [18]. Currently, however, the inhibitors topically for the treatment of eye diseases do not apply.

Task this is th invention is to prevent the development of microcirculatory disorders, as well as the recovery of disturbed microcirculation in tissue structures of the eye. Another important feature of the invention, in addition to the anti-ischemic action, is the ability to improve the course of reparative processes in damages of the tissues, to prevent the development of deep ulcers, to accelerate the healing process. This is especially important for the treatment of eye injuries, given the fine structural organization of the tissue and the need to maintain transparency in a number of tissues and media of the eye.

To achieve the objectives of the proposed pharmaceutical composition for topical application, the active principle of which is an ACE inhibitor. The inhibitor must be in the active form, for example, contains a sulfhydryl group (captopril, metoprolol, zofenoprilat and others), containing carboxialkilnuyu group (enalaprilat, lisinopril, ramiprilat, trandolaprilat and others) or containing fastinlow group (fosinoprilata and others). The composition may contain as a medium of known ophthalmic carriers, including water containing a buffering agent, an isotonic mixture of antibacterial components, preservatives, prolongator, thickeners, gels. The composition can also contain one or more additional permitted therapeutic medications, such as antibiotics, macro - and microelements, vitaminee vitamin-like means, blockers, etc. of the Claimed composition is prompted topically as eye drops, spray, or local injection.

Testing of pharmaceutical compositions was carried out on rabbits. Experimental investigations were carried out on models of eye burns of different localization, which are accompanied by ischemia of the conjunctiva, corneal ulcers and inflammation, as well as on models of diabetes in rabbits, at an early stage which were impaired microcirculation in the conjunctiva. We found that in experimental animals in the tear fluid, the metabolism which reflects the nature of the flow of biochemical processes in the eye, when the eye injuries and diabetes increases enzyme activity. The correlation between the activity of the enzyme in tears and severity of clinical manifestations of the pathological process. Enzyme activity in the tear was assessed by the initial velocity of hydrolysis of the substrate Cbz-Phe-His-Leu, determining the reaction product (His-Leu) fluorimetrically after modification of ortho-phthalic aldehyde [19]. The clinical picture of the disease was evaluated using biomicroscopy, a photographic recording of the vessels of the limb, ophthalmoscopy and calipatria vessels. Estimated well depth and size of the ulceration, the degree of edema and hyperemia age, presence of discharge, infiltration fabric, length and density of the newly formed with the perception, signs of uveitis.

The concentration of the enzyme inhibitor can vary from 1 mg/ml to 20 mg/ml depending on the surface or interior of the eye tissue affected.

The pharmaceutical composition has the following composition (wt.)

Example 1(mg/ml)
Captopril1,2
One-deputizing sodium phosphate6,0
Disubstituted sodium phosphate0,88
Benzalconi chloride0.3 to 1.0
Sodium chloride3,0-9,0
Distil. water1 ml

Example 2

Lisinopril20
Sodium hydroxidepH 6,0-7,5
Benzalconi chloride0.3 to 1.0
Sodium chloride3,0-9,0
Distil. water1 ml

Example 3

Lisinopril5
Sodium hydroxidepH 6,0-7,5
Sodium chloride3,0-9,0
Calcium chloride20
Distil. water1 ml

Example 4

Captopril2One-deputizing sodium phosphate6,0Disubstituted sodium phosphate0,88Sodium chloride3,0-9,0Riboflavin0,2Distil. water1 ml

Example 5

Enalaprilat10
Sodium hydroxidepH 6,0-7,5
Sodium chloride3,0-9,0
Ciprofloxacin3,0
Distil. water1 ml

Example 6

Enalaprilat20
Sodium hydroxidepH 6,0-7,5
Sodium chloride3,0-9,0
Timolol maleate2,5-5,0
Distil. water1 ml

Example 7

Enalaprilat1,0
Sodium hydroxidepH 6,0-7,5
Sodium chloride3,0-9,0
The methylcellulose10
Distil. water1 ml

Experiments on animals have shown that m is the local application of the claimed composition improves microcirculation in the ischemic processes, reduces symptoms of inflammation, improves outcomes and accelerates the course of reparative processes after injury.

Given that the physiological characteristics of the eye of rabbit and man are identical, this pharmaceutical composition can be recommended for use in veterinary medicine and in the clinic.

LITERATURE

1. Morozov I., Yakovlev A.A. Pharmacotherapy of eye diseases: a Handbook. Moscow, (2001), 336 S.

2. Patent EP 1297849 A1 (2001).

3. Patent US 4795423 (1989).

4. Patent US 5431907 (1995).

5. Mashkovsky PPM Medicines. M, UN "New Wave", (2002) vol. 1, 420-425.

6. S.C.Brodovsky, C.A.McCarty, G.Snibson et al. Management of alkali burns. Ophtalmology (2000) 107, 1829-1835.

7. Patent RU 2145229 C1, (1997).

8. Patent RU 2073523 C1, (1977).

9. Tereshchenko S.N. EUROPA opens new horizons for the use of ACE inhibitors. Pharmacotherapy in cardiology (2003) 05.

10. Drexler H., Kurz, S. et al. Am. J. Cardiol (1995) 76, 13E-18E.

11. Yusuf S, Lonn E. Eur. Heart J. (1998) 19 (Suppl. J.), J36-J44.

12. Jacobsson L., Persson K, Aberg G., Anderson R., Karlberg C., Olsson A.J. Antiatherosclerotic effects of the angiotensin-converting enzyme inhibitors captopril and fosinopril in hypercholesterolemic minipigs. Cardiovasc. Pharmacol. (1994) 24, 670-677.

13. L.H.Opie. Angiotensin-converting enzymes inhibitors: the advance continius. N.-Y., 1999, 275 p.

14. Deinum J., Derkx F.H., Danser A.H., Schalekamp M.A. Identification and quantification of renin and prorenin in the bovine eye. Endocrinology (1990) 126, 1673-1682.

15. Patent US 4656188 (1987).

16. Chaturvedi H., Sjolie AK, J.M. Stephenson et al. Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes. The EUCLID Study Group. EURODIAB Controlled Trial of Lisinopril in nsulin-Dependent Diabetes Mellitus. Lancet (1998) 351, 28-31.

17. Patent EUR. 0099239 (1984).

18. RF patent 2119314 (1996).

19. Eliseeva J.E., Orekhovich V.N., Pavlikhina L.V. isolation and properties of carboxykinase (peptidyl-dipeptidase) from the lung tissue of a bull. (1976) Biochemistry, 41, 506-512.

1. Pharmaceutical composition for the treatment and prevention of eye diseases associated with impaired microcirculation and/or inflammatory processes, characterized by the fact that it is intended for local use and contains as active ingredient an inhibitor of angiotensin-converting enzyme and the target additive, the content of active ingredient is from 1 to 29 mg/ml

2. The composition according to claim 1 can be made in the form of eye drops, spray, gel, solution for local injection.

3. The composition according to claim 1, where the target additives can be used in water containing a buffering agent, an isotonic mixture, the preservative, the prolongator.

4. The composition according to claim 1 further comprises drugs selected from the group: antibiotics, macro - and micronutrients, vitamins, blockers.



 

Same patents:

FIELD: veterinary medicine.

SUBSTANCE: composition comprises solution for per os introducible to animals. The solution contains Phenasal and additives. Phenasal is applied as solution of its salt in aprotonic bipolar hydroxyl-containing solvents and bases.

EFFECT: high therapeutic activity; reduced Phenasal consumption; enhanced effectiveness of treatment.

4 cl, 2 tbl

Haemostatic agent // 2275201

FIELD: pharmaceutical industry, in particular haemostatic agent.

SUBSTANCE: claimed agent represents aqueous solution, containing 2-150 g of zinc polyacrylate, 10-100 g sodium alginate and 1-30 of acetic acid in 1 l of distilled water. Agent of present invention being in contact with blood and tissues provides film formation 30 s.

EFFECT: haemostatic agent of improves quality.

FIELD: pharmaceutical industry, in particular agent for treatment of joint diseases in form of injections.

SUBSTANCE: claimed agent contains glucoseamine salt, preservative, non-ionic surfactant, in particular oleic acid and polyoxyethylated sorbitan monoether, and water.

EFFECT: agent for treatment of joint diseases of improved effectiveness combining chondroprotevtive action with high pharmacokinetic properties and biological availability.

3 cl, 3 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: remedy has saccharides like chondroitin sulfate (0.5-20.0% by mass) and salt of glycosamine (1.0-25.0% by mass), preservative (0.1-2.0% by mass), nonionogenic substance like monoester of oleic acid and polyoxyethylized sorbitan (1.0-5.0% by mass), and water (the rest).

EFFECT: increased active substances bioavailability and diffusion rate into articulation zone.

3 cl, 3 tbl

FIELD: medicine, in particular preparation of quick closing insulin preparations for treatment of diabetus mellitus.

SUBSTANCE: claimed method includes preparation of solutions containing insulin and ancillary substances, blending thereof, sterilizing filtration and bottling into flacks. Previously buffer solution containing 2.35-2.45 mg of disubstituted sodium phosphate; 2.25-3.0 mg m-cresol, and 15-17 mg of glycerol as calculated to 100 U of insulin is prepared, then insulin solution is prepared at 3.1-3.3 and added to buffer solution. Solutions are blended at agitation for 10-20 min, pH is adjusted to 7.2-7.4 and water is added up to finish insulin concentration of 100 IU/ml.

EFFECT: human gene engineered insulin of prolonged storage time without losses of physical, chemical and biological properties.

2 ex, 1 tbl

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to therapy of topical suppurative-inflammatory processes. Agent represents an aqueous isoosmotic solution comprising 0.25% of novocaine, 1% of cefazolin sodium salt and 0.77% of sodium chloride. Invention provides the development of optimal conditions for safety mechanical moving of agent in intercellular space under positive hydrodynamic pressure in the permanent state from the injection point in direction to side of deeply localized pathological focus and eliminates the pain component of the inflammatory response.

EFFECT: valuable medicinal properties of agent.

2 ex

FIELD: medicine, transfusion, infusion therapy.

SUBSTANCE: invention proposes antioxidant representing hydroxyethylated starch or pullulan chemically modified with steric-hindranced phenol. Fragment of steric-hindranced phenol represents β-(4-hydroxy-3,5-di-tert.-butylphenyl)-propionyl or β-(4-hydroxy-3,5-di-tert.-butylphenyl)-α-(N-benzoylamino)-acryloyl and its content is from 2 wt.-% up to limit solubility of polymer in water and doesn't exceed 10 wt.-% for modified hydroxyethylated starch and 12 wt.-% for modified pullulan. Plasma substitute showing antioxidant and antiradical activity represents indicated polymeric antioxidant in physiological solution or Ringer-Lock solution in plasma substitute based on the corresponding non-modified polymer. Also, invention describes a method for maintenance the level of arterial pressure and processes of antioxidant protection of body under condition of acute blood loss by using the indicated plasma substitute. As compared with analogs, new plasma substitute shows two kinds of activity: antioxidant and antiradical that are sufficient for operative increase of arterial pressure and its stabilization at the level of physiological norm, and for decreasing amount of free radicals and enhancing antioxidant protection of body in acute massive blood loss.

EFFECT: valuable medicinal properties of agents.

5 cl, 6 tbl, 4 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to a medicinal agent representing solution of the compound N-[O-(p-pivaloyloxybenzenesulfonylamino)benzoyl]glycine of the formula (I):

in common with at least one regulator of pH value chosen from the group consisting of trisodium phosphate hydrate, sodium hydroxide and potassium hydroxide in the amount providing pH 7.0-9.0. Proposed medicinal agent represents injection formulation and designated for treatment of state with the proposed compound that is an inhibitor of enzyme elastase and improves the disease state. Also, invention relates to the ready medicinal formulation of this agent representing the injection formulation prepared by drying and freezing out. Invention provides acceptable solubility and stability of the compound (I) in solution and as a component of ready injection medicinal formulations.

EFFECT: improved and valuable pharmaceutical properties of medicinal formulation.

15 cl, 6 tbl, 1 dwg, 6 ex

FIELD: special compositions.

SUBSTANCE: invention relates to active composition for regional effect that comprises active compounds for regional effect and taken in the amount from about 0.001 to about 5 wt.-%, anionic surface-active substance taken in the amount from about 0.1 to about 15 wt.-%, hydrotrop taken in the amount from about 0.5 to about 35 wt.-%, water-soluble hydrogen-containing solvent taken in the amount from about 0.5 to about 25 wt.-%, and from 0 to about 5 wt.-% of secondary surface-active substance, and water. Also, invention relates to a method for surface cleansing and precipitation of active compound for regional effect on indicated surface. The composition provides rapid and effective precipitation of active compound for regional effect in combination with producing effective residual effect.

EFFECT: improved and valuable properties of compositions.

15 cl, 3 tbl, 29 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to a pharmaceutical preparation comprising concentrated aqueous solution of α-2,4-disulfophenyl-N-tert.-butylnitrone disodium salt wherein the concentration of α-2,4-disulfophenyl-N-tert.-butylnitrone disodium salt in solution is in the ranges from 100 to 600 mg/ml, and pH value is in the range from 7 to 9.5. Also, invention relates to a method for preparing this preparation. Prepared solutions of α-2,4-disulfophenyl-N-tert.-butylnitrone disodium salt show high stability and elicit antibacterial properties that allow avoiding addition of preserve agents.

EFFECT: improved and valuable pharmaceutical properties of preparations.

17 cl, 16 tbl, 12 ex

FIELD: medicine.

SUBSTANCE: method involves introducing solutions into articulation to inhibit cartilage destruction. The solutions contain: (a) therapeutically effective amount of anabolic chondroprotective agent selected from a group composed of interleukine antagonists stimulating anabolic processes in cartilage, members of superfamily transforming growth β-factor including TGF-β agonists and agonists of morphogenous bone proteins stimulating anabolic processes in cartilage, insulin-like fibroblast growth factors stimulating anabolic processes in cartilage; (b) therapeutically effective amount of a cartilage catabolism inhibitor selected from a group composed of antagonists of interleukine-1-receptors, antagonists of TGF-α-receptors, specific cyclo-oxygenase-2 inhibitors, nitrogen oxide synthase inhibitors, nuclear kB factor inhibitors, matrix metalloproteinase inhibitors, cell adhesion molecules including integrin agonists and integrin antagonists, anti-chemotaxis agents, intracellular signal transmission inhibitors including protein kinase C inhibitors and tyrosine protein kinase inhibitors, intracellular (protein-tyrosine)-phosphatases and SH2-domain inhibitors inhibiting cartilage catabolism. The solution is locally supplied.

EFFECT: stimulated integration and modulation of anti-inflammatory synoviocyte and chondrocyte responses.

54 cl, 9 dwg, 30 tbl

FIELD: pharmaceuticals industry, in particular new method for production of alpha-1-antitrypsin and pharmaceutical product containing the same.

SUBSTANCE: alpha-1-antitrypsin is isolated from Cohn fraction IV-1 by solubilization. Then protein admixtures and eventual viral particles are removed by polyethylene glycol, target protein is precipitated with zinc salt, viral inactivation using solvent/detergent is carried out, product is fractionated using Q-sepharose, and non-active alpha-1-antitrypsin is removed with S-sepharose to produced target product. Said product represents concentrate of human serum active alpha-1-antitrypsin having purity more than 98 % and specific activity not less than 40 IU/mg in 0.15 M sodium chloride solution.

EFFECT: increased yield of high pure active alpha-1-antitrypsin.

4 cl

FIELD: biotechnology, medicine, pharmacy, veterinary science.

SUBSTANCE: method involves addition of DEAE-Sephadex A-50 to cryosupernatant from human blood plasma, incubation, filtration and addition of QAE-Sephadex to filtrate followed by incubation. Filtered off precipitate of QAE-Sephadex is subjected for successive step-by-step washing out with buffer solution at pH 5.5 and 7.5, elution at pH 7.7 and dialysis. Then PEG-6000 is added to dialyzed solution to the concentration 12%, solution is incubated and centrifuged. To the prepared supernatant glycine is added to the final concentration 100 mM and lysine is added to the final concentration 10 mM at pH 7.2, then Twin-80 is added and pH value is corrected to 6.8-7.2 followed by addition of tri-n-butyl phosphate to the final concentration 0.3%. Prepared suspension is stirred, subjected for chromatography on DEAE-Sepharose FF at pH 7.0, chromatography on Zn-chelating Sepharose FF at pH 7.5 and the end product with specific activity from 7.5 ± 0.5 U/mg of protein and above, and with the final concentration of lysine 10 mM, not less, and with the final concentration of glycine 100 mM, not less. Method provides safety of activity in antiviral treatment and preparing product containing the natural C-1 esterase inhibitor from blood plasma with high specific activity.

EFFECT: improved method for preparing.

6 cl, 2 dwg, 1 ex

FIELD: medicine, anesthesiology, traumatology, orthopedics, thoracic surgery.

SUBSTANCE: about 1.5-2 min before spreading the affected lung it is necessary to deepen anesthesia due to injecting phenthanyl at the dosage of 10-12 mcg/kg body weight. The present innovation provides safety of operations of ventral spondyledesis out of transthoracic and thoracodiaphragmatic accesses, stability of arterial pressure level and patient's heart rate, decreases stress loading upon a patient that, in its turn, favors the prophylaxis of intraoperative complications.

EFFECT: higher efficiency of anesthesiological protection.

2 cl, 1 ex

FIELD: pharmaceutics.

SUBSTANCE: the set of components is suggested containing: (a) pharmaceutical preparation including low-molecular thrombin inhibitor or its pharmaceutically acceptable derivative in the mixture with pharmaceutically acceptable adjuvant, solvent or carrier; and (b) pharmaceutical preparation including pre-medicine of low-molecular thrombin inhibitor or pharmaceutically acceptable derivative of this pre-medicine in the mixture with pharmaceutically acceptable adjuvant, solvent or carrier, where components (a) and (b), each of them, should be taken in the form suitable to be introduced together; it is, also, suggested to apply this set of components for treating the state at which it is necessary or preferably to inhibit thrombin. The innovation enables to treat thrombotic states such as thrombosis of deep veins and pulmonary embolism.

EFFECT: higher efficiency of application.

30 cl, 1 tbl

FIELD: pharmaceutical industry, medicine.

SUBSTANCE: invention relates to peroral immediate-released drug in solid form, containing low molecular thrombin inhibitor based on peptide with pH-depending solubility. Claimed drug has size particle less than 300 mum and contains combination of microcrystal cellulose and sodium glycolate starch in amount of more than 35 mass % (calculates as preparation mass).

EFFECT: drug with reduced dependence of thrombin inhibitor dissolution from pH and increased releasing rate from tablet.

17 cl, 3 ex, 3 dwg

FIELD: medicine, pharmaceutics, pharmacology.

SUBSTANCE: one should apply mammalian anti-HBP-antibodies. The ways are being suggested to identify monoclonal antibody bound, at least, with one epitope upon native HBP (heparin-binding protein) and methods to detect whether a mammal produces HBR being bound with a monoclonal antibody and, also, the kits for the above-mentioned purpose. The present innovation provides the opportunity to apply the mentioned antibodies in preventing and treating disorders associated with bradykinin releasing.

EFFECT: higher efficiency of application.

25 cl, 11 dwg, 3 ex, 1 tbl

FIELD: pharmaceutical chemistry.

SUBSTANCE: invention relates to (i) essentially crystalline melagatran in the form of hydrate, which is characterized by x-ray diffraction pattern on powder having crystalline peaks with following d values: 21.1, 10.5, 7.6, 7,0, 6.7, 6.4, 6.2, 5.7, 5.4, 5.3, 5.22, 5,19, 5.07, 4.90, 4.75, 4,68, 4.35, 4.19, 4.00, 3.94, 3.85, 3.81, 3.73, 3.70, 3.63, 3.52, 3.39, 3.27, 3,23, 3.12, 3.09, 3.06, 2.75, 2.38, and 2.35 Å and/or water content 4.3%; and (ii) essentially crystalline melagatran in the form of anhydrate, which is characterized by x-ray diffraction pattern on powder having crystalline peaks with following d values: 17.8, 8.9, 8.1, 7.5, 6.9, 6.3, 5.9, 5.6, 5.5, 5.4, 5.3, 5.2, 5.0, 4.71, 4.43, 4.38, 4.33, 4.14, 4.12, 4.05, 3.91, 3.73, 3.61, 3.58, 3.56, 3.47, 3.40, 3.36, 3,28, 3.24, 3.17, 3.09, 3.01, 2.96, 2.83, 2.54, 2.49, 2.41, 2.38, and 2.35 Å. Invention also relates to a method for preparation of indicated form, a method for interconversion of anhydrite form, to use of indicated compounds as pharmaceutical agent, and to preparation of drugs. Pharmaceutical preparation is suitable for treatment of condition, in case of which inhibition of thrombin is needed or desirable. Invention provides a method for treatment of such condition.

EFFECT: increased chemical stability and solid state stability as compared to amorphous forms of melagatran.

14 cl, 4 dwg, 3 tbl, 9 ex

The invention relates to pharmaceutical industry and relates to the creation of a means for inhibiting reproduction enveloped viruses

FIELD: pharmaceutical chemistry.

SUBSTANCE: invention relates to (i) essentially crystalline melagatran in the form of hydrate, which is characterized by x-ray diffraction pattern on powder having crystalline peaks with following d values: 21.1, 10.5, 7.6, 7,0, 6.7, 6.4, 6.2, 5.7, 5.4, 5.3, 5.22, 5,19, 5.07, 4.90, 4.75, 4,68, 4.35, 4.19, 4.00, 3.94, 3.85, 3.81, 3.73, 3.70, 3.63, 3.52, 3.39, 3.27, 3,23, 3.12, 3.09, 3.06, 2.75, 2.38, and 2.35 Å and/or water content 4.3%; and (ii) essentially crystalline melagatran in the form of anhydrate, which is characterized by x-ray diffraction pattern on powder having crystalline peaks with following d values: 17.8, 8.9, 8.1, 7.5, 6.9, 6.3, 5.9, 5.6, 5.5, 5.4, 5.3, 5.2, 5.0, 4.71, 4.43, 4.38, 4.33, 4.14, 4.12, 4.05, 3.91, 3.73, 3.61, 3.58, 3.56, 3.47, 3.40, 3.36, 3,28, 3.24, 3.17, 3.09, 3.01, 2.96, 2.83, 2.54, 2.49, 2.41, 2.38, and 2.35 Å. Invention also relates to a method for preparation of indicated form, a method for interconversion of anhydrite form, to use of indicated compounds as pharmaceutical agent, and to preparation of drugs. Pharmaceutical preparation is suitable for treatment of condition, in case of which inhibition of thrombin is needed or desirable. Invention provides a method for treatment of such condition.

EFFECT: increased chemical stability and solid state stability as compared to amorphous forms of melagatran.

14 cl, 4 dwg, 3 tbl, 9 ex

Up!