US20010021723A1 - Histochrome and its therapeutic use in ophthalmology - Google Patents
Histochrome and its therapeutic use in ophthalmology Download PDFInfo
- Publication number
- US20010021723A1 US20010021723A1 US09/832,789 US83278901A US2001021723A1 US 20010021723 A1 US20010021723 A1 US 20010021723A1 US 83278901 A US83278901 A US 83278901A US 2001021723 A1 US2001021723 A1 US 2001021723A1
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- United States
- Prior art keywords
- histochrome
- echinochrome
- retina
- treatment
- eye
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 230000001225 therapeutic effect Effects 0.000 title description 3
- NCFUWNUATANZPH-UHFFFAOYSA-N echinochrome A Natural products OC1=C(O)C(O)=C2C(=O)C(CC)=C(O)C(=O)C2=C1O NCFUWNUATANZPH-UHFFFAOYSA-N 0.000 claims abstract description 16
- 229930190208 echinochrome Natural products 0.000 claims abstract description 15
- 239000000644 isotonic solution Substances 0.000 claims abstract description 4
- 239000000243 solution Substances 0.000 claims description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Inorganic materials [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 239000011780 sodium chloride Substances 0.000 claims description 4
- SOBHUZYZLFQYFK-UHFFFAOYSA-K trisodium;hydroxy-[[phosphonatomethyl(phosphonomethyl)amino]methyl]phosphinate Chemical class [Na+].[Na+].[Na+].OP(O)(=O)CN(CP(O)([O-])=O)CP([O-])([O-])=O SOBHUZYZLFQYFK-UHFFFAOYSA-K 0.000 claims description 3
- 239000004615 ingredient Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 13
- 210000001525 retina Anatomy 0.000 abstract description 13
- 210000004087 cornea Anatomy 0.000 abstract description 6
- 206010030113 Oedema Diseases 0.000 abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 5
- 239000012528 membrane Substances 0.000 abstract description 4
- 230000004054 inflammatory process Effects 0.000 abstract description 3
- 230000002792 vascular Effects 0.000 abstract description 3
- 239000007972 injectable composition Substances 0.000 abstract description 2
- 230000004060 metabolic process Effects 0.000 abstract description 2
- 150000003839 salts Chemical class 0.000 abstract description 2
- 230000001228 trophic effect Effects 0.000 abstract description 2
- 206010061218 Inflammation Diseases 0.000 abstract 1
- 208000032843 Hemorrhage Diseases 0.000 description 9
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- JPGDYIGSCHWQCC-UHFFFAOYSA-N emoxypine Chemical compound CCC1=NC(C)=CC=C1O JPGDYIGSCHWQCC-UHFFFAOYSA-N 0.000 description 4
- 230000004438 eyesight Effects 0.000 description 4
- 210000001328 optic nerve Anatomy 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 210000004127 vitreous body Anatomy 0.000 description 3
- 206010015911 Eye burns Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 208000022873 Ocular disease Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 230000023555 blood coagulation Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- DNRFNICCPHGYAX-UHFFFAOYSA-N 6-ethyl-2,3,5,7,8-pentahydroxynaphthalene-1,4-dione Chemical compound O=C1C(O)=C(O)C(=O)C2=C(O)C(CC)=C(O)C(O)=C21 DNRFNICCPHGYAX-UHFFFAOYSA-N 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- 208000009043 Chemical Burns Diseases 0.000 description 1
- 206010010254 Concussion Diseases 0.000 description 1
- 208000006069 Corneal Opacity Diseases 0.000 description 1
- 206010011033 Corneal oedema Diseases 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 241000257465 Echinoidea Species 0.000 description 1
- 208000031969 Eye Hemorrhage Diseases 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 241001123008 Leukoma Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 208000009344 Penetrating Wounds Diseases 0.000 description 1
- 208000037111 Retinal Hemorrhage Diseases 0.000 description 1
- 206010038848 Retinal detachment Diseases 0.000 description 1
- 206010053615 Thermal burn Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 208000014306 Trophic disease Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 208000005298 acute pain Diseases 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 210000002159 anterior chamber Anatomy 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000004856 capillary permeability Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000009514 concussion Effects 0.000 description 1
- 210000000795 conjunctiva Anatomy 0.000 description 1
- 208000021921 corneal disease Diseases 0.000 description 1
- 201000004778 corneal edema Diseases 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 206010023332 keratitis Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 208000001491 myopia Diseases 0.000 description 1
- 230000004379 myopia Effects 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 238000005502 peroxidation Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000003289 retinoprotective effect Effects 0.000 description 1
- 150000003385 sodium Chemical class 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000036575 thermal burns Effects 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Classifications
-
- 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
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
-
- 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
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
Definitions
- the present invention relates to medicine and, more specifically, to a novel pharma-ceutical composition useful in the treatment of ophthalmic diseases.
- antioxidants are used increasingly in the treatment of ocular diseases. These compounds are able to alleviate inflammatory resorptive phenomena, to accelerate epithelization of the cornea and to reduce the incidence of dangerous complications that may result in the death of the eye.
- Emoxipin (2-ethyl-6-methyl-4-oxypyridine) is known by its ability to reduce the capillary permeability and to inhibit blood coagulation. Injection of a 1% solution of this compound facilitates the resorption of intraocular hemorrhages.
- Emoxipin is clinically used in the treatment of chemical and thermal burns of the eye and in the keratoplasty of burn-related leukomas.
- monitoring of the blood coagulation system is required in the course of Emoxipin therapy, since this compound is liable to cause reccurrent hemorrhages (Egorov E. A., Shvedova A. A., Obraztsova I. S. Results of a clinical study of the antioxidant Emoxipin in the treatment of eye diseases. Vestnik Oftalmologii, 1989, No. 5, pp. 52-55, in Russian).
- the objective of the present invention is to provide a novel and highly effective pharma-ceutical composition for the treatment of ophthalmic diseases, which would also meet the requirements that apply to injectable formulations.
- the pharmaceutical composition of the present invention is based on echinochrome and has been specifically developed for the treatment of ophthalmic diseases.
- the composition of the present invention contains an 0.02% isotonic solution of di- and trisodium salts of echinochrome.
- the inventors established appropriate conditions under which a chemical interaction between the salt of a weak acid (sodium carbonate) and an organic compound (echinochrome) produces water-soluble sodium derivatives of echinochrome, in which 2 to 3 sodium ions are present per molecule of echinochrome.
- Echinochrome or 2,3,5,6,8-pentahydroxy-7-ethyl-1,4-naphthoquinone, is produced from a natural source (sea urchins, Latin echini), or by chemical synthesis.
- the novel pharmaceutical composition Histochrome (trade mark) represents an isotonic solution for injections, containing a mixture of di- and trisodium salts of echinochrome in an amount of 0.018 to 0.022% in an 0.9% sodium chloride solution.
- the solution thus prepared is sterilized by filtration through membrane filters and poured into 1 ml ampoules under aseptic conditions in an inert atmosphere.
- the ready-to-use composition is packaged in batches of 5-10 ampoules into boxes lined with PVC and aluminum foil. The boxes are placed into packs and 10-60 packs are placed into cardboard boxes and labeled in accordance with the requirements.
- the composition is stored protected from light at a temperature not exceeding 25° C. It has a shelf life of 2 years.
- composition is a yellow-brown transparent liquid.
- the content of echinochrome which is formed when Histochrome is acidified with hydrochloric acid, is determined spectrophotometrically.
- the optical density of a sample of the composition in acidified alcohol is compared with the optical density of a standard solution with a known concentration of echinochrome prepared under identical conditions.
- the active ingredient is identified by its spectrum in acidified ethanol, which in the range of 250 to 600 nm has two absorption maxima (342 ⁇ 2 nm and 468 ⁇ 2 nm) and two absorption minima (295 ⁇ 2 nm and 394 ⁇ 2 nm).
- the isotonocity of the sample is checked by mercurometric titration of sodium chloride using diphenilcarbazone as an indicator.
- the content of sodium chloride in the sample is in the range of 0.87% to 0.93%, and the pH is 6.5 to 7.5.
- composition is sterile. Histochrome itself has a marked antimicrobial activity.
- the composition of the present invention is effective in the treatment of inflammatory diseases of the cornea, vascular membrane and retina of the eye; in the treatment of trophic disorders and resorption of hemorrhages in the vitreous body and retina.
- Histochrome may be used in proliferative processes, to reduce edema and to improve epithelization, as well as in the treatment of concussions and penetrating wounds of the eye.
- the composition has well-pronounced retinoprotective properties, improves characteristics of degenerative processes in the retina and the optic nerve. Histochrome was also found to act as an anticataractic agent.
- the composition of the present invention was clinically studied in humans. Histochrome was used to treat hyphemia. Hyphemia is a complication that occurs after surgical removal of a cataract in the presence of severe myopia, hypertension-based glaucoma stage 2 or 3, amotio retinae after repeated surgery. Hyphemia cases covered the range from 1 mm up to a complete filling of the entire anterior eye chamber with blood. Hyphemia was resolved in 12 out of 14 patients treated. The following pattern of the resorption of hemorrhages was observed by biomicroscopy: the first 2-3 injections of Histochrome were followed by loosening and lique-faction of the blood clot, but its volume was not significantly reduced under these conditions. During the subsequent 2-3 days a rapid resorption occurred and no traces of hemorrhage remained on day 5 and 6 in the anterior chamber. In this group of patients the acuity of vision increased from 0.05 to 0.4 in 8 cases (57.1%).
- Histochrome administration parabulbarly (5-6 injections) to patients with diabetic retinopathy resulted in a reduction of edema zones and resorption of hemorrhages in the retina (a decrease both in terms of surface area and height).
- the acuity of vision increased from 0.03 to 0.6.
- Electrophysical studies revealed an improved functioning of the optic nerve and the retina. Histochrome improved metabolical processes in the optic nerve and the retina and produced a protective effect. Considering the fact that diabetes-related ocular diseases tend to progress further, even a slight improvement of vision is regarded as a positive factor.
- the resorption of subretinal hemorrhages and reduced edemas in the retina provide good conditions for carrying out an effective and high-quality laser-induced coagulation of the retina.
- a positive therapeutic effect of Histochrome was also oserved in patients with keratitis. They were given an 0.02% Histochrome solution in the form of daily instillations 4 to 5 times a day. From the very first days of the histochrome therapy reductions in the pericorneal infections in the conjunctiva and in the corneal edema were observed. Epithelization of the cornea occurred 3-4 days earlier that in the case of treatment with conventional therapeutic compositions.
- composition of the present invention is prescribed for the treatment of diseases associated with disturbances in the metabolic and inflammatory processes in the retina, vascular membrane and cornea of the eye, for improving trophic functions, for reducing edema and for accelerating epithelization.
- An 0.02% histochrome solution is administered in the form of subconjunctival and parabulbar injections in doses of 0.3-0.5 ml. Injections are made daily or every other day, depending on indications.
- the Histochrome solution from ampoules is used in the form of instillations, 2 drops, 4-5 times a day.
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- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Ophthalmology & Optometry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Steroid Compounds (AREA)
Abstract
A pharmaceutical composition is provided which comprises an isotonic solution of an 0.02% mixture of di- and trisodim salts of echinochrome (Histochrome). It meets the requirements that apply to injectable formulations. Histochrome administration to human patients normalizes metabolic processes and eliminates inflammation in the retina, vascular membrane and cornea of the eye, improves trophic functions, reduces edema and accelerates epithelization.
Description
- The present invention relates to medicine and, more specifically, to a novel pharma-ceutical composition useful in the treatment of ophthalmic diseases.
- At present, the role of free-radical peroxidation in the development of various diseases of the retina, optic nerve and other structures of the eye is well appreciated. For this reason, antioxidants are used increasingly in the treatment of ocular diseases. These compounds are able to alleviate inflammatory resorptive phenomena, to accelerate epithelization of the cornea and to reduce the incidence of dangerous complications that may result in the death of the eye.
- The synthetic antioxidant Emoxipin (2-ethyl-6-methyl-4-oxypyridine) is known by its ability to reduce the capillary permeability and to inhibit blood coagulation. Injection of a 1% solution of this compound facilitates the resorption of intraocular hemorrhages. Emoxipin is clinically used in the treatment of chemical and thermal burns of the eye and in the keratoplasty of burn-related leukomas. However, monitoring of the blood coagulation system is required in the course of Emoxipin therapy, since this compound is liable to cause reccurrent hemorrhages (Egorov E. A., Shvedova A. A., Obraztsova I. S. Results of a clinical study of the antioxidant Emoxipin in the treatment of eye diseases. Vestnik Oftalmologii, 1989, No. 5, pp. 52-55, in Russian).
- Also known in the prior art is the use of an 0.5% echinochrome solution in the treatment of eye burns (RU 2 038 088). Subconjunctival and parabulbar administration of an 0.5%-echinochrome solution to rabbits showed that it is able to facilitate epithelization of the cornea at early stages of the treatment of eye burns and to alleviate inflammatory processes in the eye.
- However, clinical studies using an 0.5% echinochrome solution showed that patients experienced acute pain at the time of administration.
- The objective of the present invention is to provide a novel and highly effective pharma-ceutical composition for the treatment of ophthalmic diseases, which would also meet the requirements that apply to injectable formulations.
- The pharmaceutical composition of the present invention is based on echinochrome and has been specifically developed for the treatment of ophthalmic diseases. The composition of the present invention contains an 0.02% isotonic solution of di- and trisodium salts of echinochrome. The inventors established appropriate conditions under which a chemical interaction between the salt of a weak acid (sodium carbonate) and an organic compound (echinochrome) produces water-soluble sodium derivatives of echinochrome, in which 2 to 3 sodium ions are present per molecule of echinochrome.
- Echinochrome, or 2,3,5,6,8-pentahydroxy-7-ethyl-1,4-naphthoquinone, is produced from a natural source (sea urchins, Latin echini), or by chemical synthesis.
- The novel pharmaceutical composition Histochrome (trade mark) represents an isotonic solution for injections, containing a mixture of di- and trisodium salts of echinochrome in an amount of 0.018 to 0.022% in an 0.9% sodium chloride solution.
- The solution thus prepared is sterilized by filtration through membrane filters and poured into 1 ml ampoules under aseptic conditions in an inert atmosphere. The ready-to-use composition is packaged in batches of 5-10 ampoules into boxes lined with PVC and aluminum foil. The boxes are placed into packs and 10-60 packs are placed into cardboard boxes and labeled in accordance with the requirements. The composition is stored protected from light at a temperature not exceeding 25° C. It has a shelf life of 2 years.
- The composition is a yellow-brown transparent liquid.
- The content of echinochrome, which is formed when Histochrome is acidified with hydrochloric acid, is determined spectrophotometrically. The optical density of a sample of the composition in acidified alcohol is compared with the optical density of a standard solution with a known concentration of echinochrome prepared under identical conditions.
- The active ingredient is identified by its spectrum in acidified ethanol, which in the range of 250 to 600 nm has two absorption maxima (342±2 nm and 468±2 nm) and two absorption minima (295±2 nm and 394±2 nm).
- The isotonocity of the sample is checked by mercurometric titration of sodium chloride using diphenilcarbazone as an indicator. The content of sodium chloride in the sample is in the range of 0.87% to 0.93%, and the pH is 6.5 to 7.5.
- The composition is sterile. Histochrome itself has a marked antimicrobial activity.
- The composition of the present invention is effective in the treatment of inflammatory diseases of the cornea, vascular membrane and retina of the eye; in the treatment of trophic disorders and resorption of hemorrhages in the vitreous body and retina. Histochrome may be used in proliferative processes, to reduce edema and to improve epithelization, as well as in the treatment of concussions and penetrating wounds of the eye. The composition has well-pronounced retinoprotective properties, improves characteristics of degenerative processes in the retina and the optic nerve. Histochrome was also found to act as an anticataractic agent.
- The composition of the present invention was clinically studied in humans. Histochrome was used to treat hyphemia. Hyphemia is a complication that occurs after surgical removal of a cataract in the presence of severe myopia, hypertension-based glaucoma stage 2 or 3, amotio retinae after repeated surgery. Hyphemia cases covered the range from 1 mm up to a complete filling of the entire anterior eye chamber with blood. Hyphemia was resolved in 12 out of 14 patients treated. The following pattern of the resorption of hemorrhages was observed by biomicroscopy: the first 2-3 injections of Histochrome were followed by loosening and lique-faction of the blood clot, but its volume was not significantly reduced under these conditions. During the subsequent 2-3 days a rapid resorption occurred and no traces of hemorrhage remained on day 5 and 6 in the anterior chamber. In this group of patients the acuity of vision increased from 0.05 to 0.4 in 8 cases (57.1%).
- Clinical effects of Histochrome in patients with hemophthalmia were dependent on the localization and extent of a hemorrhage, accompanying pathology, and time to onset of therapy. Minor hemorrhages in the anterior compatrment of the vitreous body were resolved rapidly and without affecting its structure in any significant manner. The resorption of hemorrhages in hemophthalmia patients was 3-4 days faster in the Histochrome-treated group than in the control group, and no visible damage of the vitreous body was apparent. Considering the fact that blood decomposition products produce toxic effects on the retina thereby disturbing its functions, a rapid resorption of hemorrhages provides favourable conditions for an active restoration of the functional capacity of the retina.
- Histochrome administration parabulbarly (5-6 injections) to patients with diabetic retinopathy resulted in a reduction of edema zones and resorption of hemorrhages in the retina (a decrease both in terms of surface area and height). The acuity of vision increased from 0.03 to 0.6. As early as after 2-3 injections the patients reported an improvement of their vision. Electrophysical studies revealed an improved functioning of the optic nerve and the retina. Histochrome improved metabolical processes in the optic nerve and the retina and produced a protective effect. Considering the fact that diabetes-related ocular diseases tend to progress further, even a slight improvement of vision is regarded as a positive factor. Moreover, the resorption of subretinal hemorrhages and reduced edemas in the retina provide good conditions for carrying out an effective and high-quality laser-induced coagulation of the retina.
- A positive therapeutic effect of Histochrome was also oserved in patients with keratitis. They were given an 0.02% Histochrome solution in the form of daily instillations 4 to 5 times a day. From the very first days of the histochrome therapy reductions in the pericorneal infections in the conjunctiva and in the corneal edema were observed. Epithelization of the cornea occurred 3-4 days earlier that in the case of treatment with conventional therapeutic compositions.
- Clinical trials of subconjunctival and parabulbar administration of Histochrome in a dose of 0.5 ml (0.02%) showed no side effects, not a single case was reported. No contraindications against the use of Histochrome were found.
- In ophthalmological practice the composition of the present invention is prescribed for the treatment of diseases associated with disturbances in the metabolic and inflammatory processes in the retina, vascular membrane and cornea of the eye, for improving trophic functions, for reducing edema and for accelerating epithelization. An 0.02% histochrome solution is administered in the form of subconjunctival and parabulbar injections in doses of 0.3-0.5 ml. Injections are made daily or every other day, depending on indications. For the treatment of corneal diseases the Histochrome solution from ampoules is used in the form of instillations, 2 drops, 4-5 times a day.
Claims (1)
1. An echinochrome-based medicinal preparation for treatment of ophthalmic diseases, characterized in that the said preparation represents an isotonic solution of di- and tri-sodium salts of echinochrome (histochrome), with ingredients being present in the following weight ratio, g:
histochrome (based on echinochrome) 0.2 g
0.9%-sodium chloride solution up to 100.0 g
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| RU98118370 | 1998-10-12 | ||
| RU98118370A RU2134107C1 (en) | 1998-10-12 | 1998-10-12 | Preparation "gistokhrom" for treatment of eye retina and cornea inflammatory sicknesses |
| PCT/RU1999/000248 WO2000021518A1 (en) | 1998-10-12 | 1999-07-21 | Drug preparation 'histochrome' for treating ocular conditions |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/RU1999/000248 Continuation WO2000021518A1 (en) | 1998-10-12 | 1999-07-21 | Drug preparation 'histochrome' for treating ocular conditions |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| US20010021723A1 true US20010021723A1 (en) | 2001-09-13 |
| US6384084B2 US6384084B2 (en) | 2002-05-07 |
Family
ID=20211102
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US09/832,789 Expired - Fee Related US6384084B2 (en) | 1998-10-12 | 2001-04-12 | Histochrome and its therapeutic use in ophthalmology |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US6384084B2 (en) |
| EP (1) | EP1121929B1 (en) |
| JP (1) | JP2002527382A (en) |
| AT (1) | ATE281157T1 (en) |
| DE (1) | DE69921678T2 (en) |
| RU (1) | RU2134107C1 (en) |
| WO (1) | WO2000021518A1 (en) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2189209C1 (en) * | 2001-01-29 | 2002-09-20 | Яблоков Михаил Геннадьевич | Modified method for applying laser keratomylesis |
| RU2226097C2 (en) * | 2002-06-18 | 2004-03-27 | Научно-исследовательский институт кардиологии Томского научного центра СО РАМН | Method for applying reperfusion therapy to acute myocardial infarction patients |
| RU2223099C1 (en) * | 2002-07-31 | 2004-02-10 | Московский научно-исследовательский институт глазных болезней им. Гельмгольца | Eye drops for treating glaucoma |
| RU2266737C1 (en) * | 2004-04-12 | 2005-12-27 | Тихоокеанский Институт Биоорганической Химии Дальневосточного Отделения Россиской Академии Наук | Method and preparation for treating the cases of hemorrhagic stroke |
| RU2498570C1 (en) * | 2012-05-03 | 2013-11-20 | Государственное бюджетное учреждение "Уфимский научно-исследовательский институт глазных болезней Академии наук Республики Башкортостан" | Cornea storage solution |
| RU2488402C1 (en) * | 2012-06-08 | 2013-07-27 | Закрытое акционерное общество "Санкт-Петербургский институт фармации" | Agent possessing anti-inflammatory and antiallergic action |
| RU2510254C1 (en) * | 2013-01-21 | 2014-03-27 | Государственное бюджетное образовательное учреждение высшего профессионального образования "Владивостокский государственный медицинский университет" Министерства здравоохранения Российской Федерации (ГОУ ВПО ВГМУ Минздрава России) | Method for postoperative rehabilitation of patients suffering glaucoma |
| RU2554776C1 (en) * | 2013-12-16 | 2015-06-27 | Федеральное государственное бюджетное учреждение "Дальневосточный научный центр физиологии и патологии дыхания" СО РАМН | Agent for correcting pulmonary tissue disorders under cytostatic exposure |
| RU2697887C1 (en) * | 2018-08-06 | 2019-08-21 | Федеральное государственное бюджетное учреждение науки Тихоокеанский институт биоорганической химии им. Г.Б. Елякова Дальневосточного отделения Российской академии наук (ТИБОХ ДВО РАН) | Agent possessing antiviral action against tick-borne encephalitis viruses and herpes simplex type i |
| RU2684783C1 (en) * | 2018-08-06 | 2019-04-15 | Федеральное государственное бюджетное учреждение науки Тихоокеанский институт биоорганической химии им. Г.Б. Елякова Дальневосточного отделения Российской академии наук (ТИБОХ ДВО РАН) | Antioxidants composition suitable for oral administration in therapy of inflammatory process in lungs |
| GR1010730B (en) | 2022-12-07 | 2024-07-25 | Εθνικο Και Καποδιστριακο Πανεπιστημιο Αθηνων, | A pharmaceutical formulation comprising polymeric micro-/nanofibers incorporating echinochrome a |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1430726A (en) * | 1974-08-13 | 1976-04-07 | V N I Khmikofarmatsevtichesky | Pharmaceutical preparations containing resorcinol deirvatives |
| AU576340B2 (en) * | 1983-12-16 | 1988-08-25 | Bislak S.A. | Therapeutic applications of 2,4,6-triiodophenol |
| RU2038088C1 (en) * | 1990-08-01 | 1995-06-27 | Тихоокеанский институт биоорганической химии Дальневосточного отделения РАН | Method for treating burned eyes |
| RU1826909C (en) * | 1990-08-01 | 1993-07-07 | Тихоокеанский Институт Биоорганической Химии Дальневосточного Отделения Ан@ Ссср | Agent possessing ability to resolve hemophthalmia |
| ES2087019B1 (en) * | 1994-02-08 | 1997-03-16 | Bobel246 S L | USE OF DERIVATIVES OF PHENOLS 2,4-DISUBSTITUTED AS INHIBITORS OF 5-LIPOXIGENASE. |
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1998
- 1998-10-12 RU RU98118370A patent/RU2134107C1/en active
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1999
- 1999-07-21 WO PCT/RU1999/000248 patent/WO2000021518A1/en active IP Right Grant
- 1999-07-21 EP EP99954548A patent/EP1121929B1/en not_active Expired - Lifetime
- 1999-07-21 JP JP2000575494A patent/JP2002527382A/en active Pending
- 1999-07-21 DE DE69921678T patent/DE69921678T2/en not_active Expired - Lifetime
- 1999-07-21 AT AT99954548T patent/ATE281157T1/en not_active IP Right Cessation
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2001
- 2001-04-12 US US09/832,789 patent/US6384084B2/en not_active Expired - Fee Related
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|---|---|
| US6384084B2 (en) | 2002-05-07 |
| DE69921678D1 (en) | 2004-12-09 |
| JP2002527382A (en) | 2002-08-27 |
| EP1121929B1 (en) | 2004-11-03 |
| DE69921678T2 (en) | 2005-10-20 |
| EP1121929A4 (en) | 2003-01-15 |
| ATE281157T1 (en) | 2004-11-15 |
| RU2134107C1 (en) | 1999-08-10 |
| EP1121929A1 (en) | 2001-08-08 |
| WO2000021518A1 (en) | 2000-04-20 |
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