Method of treating "dry" form of age-related macular degeneration
SUBSTANCE: invention relates to medicine, in particular to ophthalmology, and can be applied for treatment of "dry" form of age-related macular degeneration. Three-component complex, which contains mesenchymal stem cells, labelled with magnetic micro particles, is introduced to patient extrasclerally in macular zone projection. Cells in this complex are transposed into biological or synthetic fine-pore material. This material is fast connected with polymeric magnetic material with induction of permanent magnetic field 1.5 mT, with multipolar reversible magnetisation.
EFFECT: invention ensures improvement or stabilisation of visual functions due to directed delivery of cells to pathologic focus and holding cells in focus for the time, necessary for obtaining therapeutic effect.
The invention relates to medicine, namely to ophthalmology, and can be used for the treatment of "dry" form of age-related macular degeneration.
Age-related macular degeneration (AMD) is one of the most common and little known eye diseases, which is the main cause complete loss of vision in people over 60 years of age in industrialized countries. According to the world health organization 25-30 million people worldwide suffer from AMD. Due to the continuing aging society AMD is one of the serious health and social problems. The most common clinical form of AMD is nonexudative or "dry" form, found in 90% of cases and is characterized by a slow progressive decline in vision (Tunkasila, Gesproken, Agelisa and other Modern aspects of pathogenesis and clinic of age-related macular degeneration. // Ophthalmology. - 2005. - Vol.2. No. 1).
Existing methods of treatment of "dry" form of age-related macular degeneration (Kiseleva T.N., Lagutina, Y.M., Kravchuk E.A. and other Comprehensive treatment of age-related macular degeneration with the drug Fezam. // Ophthalmology. - 2005. No. 2. - P.63-67) are short of achievable effect.
One of the promising methods for treatment of degenerative retinal pathology may be approx the imposition of mesenchymal stem cells (MSCS), however, such methods are not yet sufficiently developed.
Stem cells have a number of significant advantages: can ensure the regeneration of damaged areas through the production of various growth factors and key metabolites; able to expand the program of proliferation and differentiation, thereby restoring the lack of active cells; can be integrated into diseased areas of the retina and form the cells of the retinal phenotype. In ophthalmology therapeutic potential of stem cells has been studied in animals with hereditary retinal pathology, close to pigmented retinitis person (Lund et al. Subretinal transplantation of genetically modified human cell lines attenuates loss of visual function in dystrophic rats. // PNAS. - 2001. - V.98. No. .17. P.9942-9947; Rander et al. Light-driven retinal ganglion cell responses in blind rd mice after neuronal transplantation. // Invest. Ophthalmol. Vis. Sci. - 2001. - V.42. - P.1057-1065; Woch et al., 2001; Sagdullaev et al. Retinal transplantation-induced recovery of retinotectal visual function in rodent model of retinitis pigmentosa. // Invest. Ophthal. Vis. Sci - 2003. - V.44. - P.1686-1695).
Although mesenchymal stem cells of an adult organism have a more restricted differentiation potential than embryonic stem cells obtained by culturing cells of a blastocyst, their use safer. In addition, from the point of view of ethics, they are more acceptable for clinical use material.
Things is a significant problem of cell therapy is targeted delivery of stem cells to pathological lesion and keeping them in it over time, required to achieve a therapeutic effect.
The objective of the invention is to increase the effectiveness of treatment of age-related macular degeneration.
The technical result is an improvement or stabilization of visual functions.
The technical result is achieved due to the fact that:
1. Use ternary complex containing MSC-labelled magnetic microparticles, translotsirovannoi in biological or synthetic porous material, which is firmly bonded with the polymer magnetic material with induction of a constant magnetic field of 1.5 MT, with multi-pole reversing the magnetization.
2. Translotsirovannoi MSC labeled with magnetic particles in biological or synthetic porous material in combination with a tight attachment to the polymer magnetic material with induction of a constant magnetic field of 1.5 MT, with multi-pole reversing magnetization provides deep penetration MSC in layers of biological or synthetic porous material, retention and even distribution of the RM in the pathological focus with extrascleral implantation of a three-component complex in the projection of the macular zone during the time required to achieve therapeutic effect, due to the interaction of magnetic fields microcash the IC and the magnetic material.
3. Extrascleral introduction ternary complex in the projection of the macular zone is accompanied directed selective adhesion of MSC in the pathological focus, which contributes to the activation of reparative processes due to engraftment of transplanted stem cells in the immediate vicinity of the damaged area.
The ability of such processes to embryonic stem cells and adult stem cells of the body shown in experiments on animals (Lamba D.A., Karl M.O., C.B. Ware, Reh T.A. Efficient generation of retinal progenitor cells from human embryonic stem cells // PNAS, 2006, v.103, n.34, pp.12769-12774. Meyer J.S, Katz M.L, Maruniak J.A, Kirk M.D. Embrionic stem cell-derived neural progenitors incorporate into degenerating retina and enhance survival of host photoreceptora // Stem Cells, 2006, v.24, n.2, pp.274-283. Fiedlander M. Fibosis and diseases of the eye // J. Clin. Invest., 2007, v.117, n.3, pp.576-586), although many of the implementation mechanisms of therapeutic effects were not studied thoroughly.
The method is as follows.
At the preliminary stage prepare ternary complex containing MSC-labelled magnetic microparticles, translotsirovannoi in biological or synthetic porous material, which is bonded with a polymeric magnetic material with induction of a constant magnetic field of 1.5 MT, with multi-pole reversing the magnetization.
MSC grown in the culture of bone marrow cells taken from p is they during diagnostic puncture of the sternum or Ilium (volume - 0.5-1.0 ml). Cultivation of rice is carried out in a special box for cell cultures using the following equipment - centrifuge with disposable sterile centrifuge tubes 50 ml, thermostat air, laminar box, inverted and conventional microscopes, automatic pipettes, cylinders with carbon dioxide and air, the camera Goryaeva to calculate cell concentration. For culturing cell source bone marrow using a sterile disposable plastic culture flasks with square bottom 25 and 150 cm2. When the reproduction of the MSC uses the following environment and solutions: medium RPMI-1640, medium 199, antibiotics: penicillin, amphotericin, a solution of L-glutamine, fetal calf serum. For 12-14 consecutive doublings (within 25-30 days) from the initial amount of undifferentiated MSCS contained in the received punctate the patient's bone marrow and approximately 103cells produced approximately (1-2)×107MSC necessary for a successful stem cell transplant.
Magnetic particles (d=2,8 µm) was injected into the cytoplasm of mesenchymal stem cells by the following method. Upon reaching 80-90% of confluently to culture MSCS add a suspension of magnetic particles. Magnetic particles pre-treated with surface-active wishes is to create conditions of penetration into the cytoplasm of a cell. Cells incubated with particles for 24 h in a CO2 incubator. After incubation, the culture medium is changed and cells 5-fold washed free from magnetic particles with Hanks solution. The efficiency of labeling MSK magnetic particles for this technology is about 90%. The viability of stem cells is 95%.
Ready ternary complex must be in the form of a circle with a diameter of 6 mm. To do this, perform the workpiece in the form of a circle 6 mm in diameter of the magnetic polymer material system samarium-cobalt or Neodym-iron-boron with the induction of a constant magnetic field of 1.5 MT with multi-pole reversing the magnetization. The thickness of the magnetic material - 0,3 mm magnetization magnetic polymer material can be produced, for example, as described in the patent of Russian Federation №2187162.
From a biological material, e.g., Dura mater or sclera, or collagen, or injection, or synthetic porous material, such as hydrogel or degele, or polyester, or silicone sponge, etc. do the workpiece in the form of a circle 6 mm in diameter, corresponding to the billet of polymeric magnetic material.
MSC-labelled magnetic microparticles layer on the surface of the workpiece from biological synthetic porous material. Then under the Petri dish with us the m ilitary material MSK, labeled magnetic particles, the sum of the external magnetic field with a strength of 30 MT. The size and shape of the external magnet corresponds to the size and shape of the workpiece from biological or synthetic material. Thus, between the external magnet and MSC containing magnetic particles, is biological or synthetic porous material. MSC containing magnetic particles, quickly and deeply translucida in layers of biological or synthetic porous material under the action of magnetic fields. Their fastening and raspletanie occurs within 1-1,5 hours after application. Fixed cells are held tightly in layers of porous material even in the current culture fluid that was simulated in the experiment using a peristaltic pump. Cells containing magnetic microparticles, proliferate, completely covering the surface of biological or synthetic porous material that proves the preservation of the functional properties of MSC.
In conclusion, the obtained structure of MSC in biological or synthetic porous material firmly fasten, for example, using suture fixation or biological glue for the preparation of magnetic polymer material.
Three-component complex is implanted extrascleral the projection of the macular area in the following way. In the upper outer quadrant 4 mm from the limbus perform incision of the conjunctiva length of 6 mm concentric limbu and with a spatula to form a tunnel in Sultanova space towards the rear pole of the eye. In the tunnel, enter the three-component complex, with a spatula produce sclerocornea to localize the position of the complex under constant control by using binocular Ophthalmoscope. Upon completion of the implantation of the conjunctiva is sutured with a continuous suture.
The invention is illustrated by the following data.
The study included 7 patients (7 eyes) with "dry" form of AMD in age from 60 to 68 years. Visual acuity before treatment in patients ranged from 0.08 to 0.12.
Patients were treated according to the proposed method.
Used three-component complexes in the form of a circle 6 mm in diameter, containing MSC-labelled magnetic microparticles, translotsirovannoi in biological material: Dura or sclera, or collagen, or synthetic porous material: hydrogel or digel, or polyester fabric or silicone sponge, which was firmly bonded using suture fixation or biological adhesive polymer magnetic material system samarium-cobalt or Neodym-iron-boron with the induction of a constant magnetic field of 1.5 MT, with multipole reverse the main magnetization.
Complexes implanted extrascleral in the projection of the macular zone. In the upper outer quadrant 4 mm from the limbus performed incision of the conjunctiva length of 6 mm concentric limbu and with a spatula shaped tunnel in Sultanova space towards the rear pole of the eye. The tunnel has introduced a three-component complex, with a spatula made sclerocornea to localize its position under constant control by using binocular Ophthalmoscope. Upon completion of the implantation of the conjunctiva sutured with a continuous suture.
12 months after treatment in all cases the visual acuity of 0.1 and 0.35, the observed increase in foveal sensitivity of the retina according to a computer perimetric studies, as well as the increase of the amplitude of a-wave and b-wave according to the macular electroretinogram, which testified to the increase of the functional activity of the retina. In the study of hemodynamics in all patients there was an increase in the average flow velocity in the ophthalmic artery, Central retinal artery and posterior short ciliary arteries.
The results remained stable during the whole observation period. The follow-up period ranged from 12 to 36 months.
Thus, the proposed method provides improved or stable is Italy visual functions in patients with "dry" form of age-related macular degeneration.
A method for the treatment of "dry" form of age-related macular degeneration, characterized in that the patient extrascleral in the projection of the macular zone implanted ternary complex containing mesenchymal stem cells labeled with magnetic microparticles, translotsirovannoi in biological or synthetic porous material, which is firmly bonded with the polymer magnetic material with induction of a constant magnetic field of 1.5 MT, with multi-pole reversing the magnetization.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pyrrol derivatives of formula (1): or a pharmaceutically acceptable salt thereof wherein the values A, R1-R3, n are specified in clause 1 of the patent claim.
EFFECT: compounds (1) inhibit activity against the interleukin IL-6 production that allows using them both in pharmaceutical compositions, and in a prophylactic drug for ocular inflammatory disease.
23 cl, 2 tbl, 22 ex
SUBSTANCE: group of inventions refers to ophthalmology. The group of inventions refers to pharmacological action of a compound functioning as a PPARr agonist on the corneal epithelial barrier function. The PPARr agonist, such as rivoglitazone, DRF-2593, GW-544 and BMS-298585, perfectly enhances the corneal epithelial barrier function in the study of enhancing the corneal epithelial barrier function, and therefore it is useful as a preventive agent or therapeutic agent for an ocular infection or eye complaints of unknown aetiology caused by the decreased corneal epithelial barrier function.
EFFECT: group of inventions provides enhancing the corneal epithelial barrier function in the patients with diabetes, age-related decrease in the corneal epithelial barrier function, and patients underwent refractive surgery, such as PRK (photorefractive keratectomy) and LASIK (laser keratomileusis in situ), and cataract surgery.
12 cl, 2 tbl, 4 ex
SUBSTANCE: invention relates to medicine, namely to ophthalmology, and can be used for inducing posterior detachment of vitreous body. For this purpose 0.1 ml of miniplasmin solution is introduced endovitreally in 4 mm from limb. Preliminarily before introduction, solution of buffer salts up to pH values of 6.8-8.0 with osmolarity 280-320 mOsm to concentration of miniplasmin in solution 1 mg/ml is added into miniplasmin, mixed, heated to temperature 37°C and kept at said temperature for from 5 to 15 minutes.
EFFECT: method ensures reduction of toxic impact on retina and vitreous body, improvement of proteolytic properties of miniplasmin and, therefore, more complete detachment of vitreous body with reduction of interference trauma.
FIELD: medicine, pharmaceutics.
SUBSTANCE: present invention refers to immunology. There are studied: a method of decreasing the load and of reducing the number of plaques in the layer of retinal ganglion cells, of reducing the total amount of soluble amyloid-beta in the layer of retinal ganglion cells and of maintaining or reducing intraocular pressure in a subject, as well as a method of preventing, treating and relieving the symptoms of ophthalmic diseases associated with amyloid-beta related pathological disorders or changes in tissues of the visual system, a diagnostic technique for such disease and predisposition thereto, and a method of monitoring the minimal residual ophthalmic disease associated with the amyloid-beta related pathological disorders or changes, involving administering the composition containing the anti-amyloid-beta antibody to the patient. The present invention can find further application in a therapy of the ophthalmic diseases.
EFFECT: what is presented is a pharmaceutical composition for treating the ophthalmic diseases containing the anti-amyloid-beta antibodies.
31 cl, 3 ex, 13 tbl, 20 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions refers to ophthalmology. A method for increasing the stability of a prostaglandin composition comprising prostaglandin, a preserving agent and pharmaceutically acceptable excipients, wherein the method comprises a stage whereat: the prostaglandin composition specified in a group consisting of Travoprost, Latanoprost, Bimatoprost and Tafluprost is packaged in a reusable low-density polyethylene container made of a low-density polyethylene wherein said low-density polyethylene container represents a low-density polyethylene bottle prepared with the use of blow-fill-seal technology, wherein low-density polyethylene resin is specified in a group consisting of Purell PE 1810 E, Purell PE 1840 H, Purell PE 3020 D, Purell PE 3040 D, Purell PE 3220 D.
EFFECT: group of inventions provides the local reusable ocular administration, the stability of the composition at room temperature up to 25°C for more than twelve months.
18 cl, 5 tbl, 1 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions relates to field of medicine, in particular to ophthalmology. Medicinal compositions for intravitreal injections and methods of treating ophthalmological disorders are disclosed. Medicinal compositions represent suspensions on the basis of low-soluble medication, such as triamcinolone acetonide. Compositions of suspensions have relatively low viscosity and are easily extracted via needle of 27- or 30-gauge needle, but are highly flocculated and can be easily redispersed.
EFFECT: group of inventions ensures improvement of vitreos body visualisation in the course of vitrectomy, treatment of ophthalmological disorders.
20 cl, 5 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions relates to field of ophthalmology. Described is application of compositions for reduction of intraocular pressure, which contain antocyanoside or including it extract, proantocyanidine or including it extract or their combinations.
EFFECT: group of inventions ensures effective application of compositions for reduction of intraocular pressure in patient.
30 cl, 1 tbl
SUBSTANCE: invention relates to medicine, namely to ophthalmology and can be used for treatment of post-LASIK keratectasia. For this purpose in space under epithelial-stromal corneal flap round recess is made from periphery to optic zone (in central zone of cornea), into which hypotonic riboflavin solution is introduced. When thickness of cornea 400 mcm and more is reached, space is filled with 0.1% riboflavin solution on 20% solution of dextran T 500 until cornea is saturated with riboflavin. After that, ultrasonic irradiation of cornea is carried out with wavelength 365 nm with intensity 3 mW/cm2 for 30 min fractionally - 6 cycles 5 each 5 minutes long. During irradiation of cornea with ultrasonic waves riboflavin solution is instilled on cornea each 2-3 minutes, additionally riboflavin solution is introduced into recess under epithelial-stromal corneal flap each 5 minutes for constant support of riboflavin solution volume in intrastromal space.
EFFECT: method ensures increase of cornea thickness to required level due to creation of conditions for fast saturation of cornea with riboflavin solution, acceleration of healing process with reduction of risk of postoperative complications development to minimum.
FIELD: medicine, pharmaceutics.
SUBSTANCE: present invention refers to a method of intraocular pressure reduction and to a method of pain control involving the administration of a therapeutic compound representing , or its tautomer or stereoisomer forms wherein X represents NH; n is equal to 2 or 3; Ra, Rb, Rc and Rd represent stable functional groups independently consisting of: 0 to 4 carbon atoms, 1 to 9 hydrogen atoms; and Re represents H or C1-4alkyl. Furthermore, the invention refers to a compound represented by formula , or to its tautomer or stereoisomer form.
EFFECT: new compound is prepared; besides, the known compounds to be applied in pain and glaucoma control are studied.
8 cl, 1 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to veterinary science, and concerns treating corneal diseases in dogs. For this purpose, mesenchymal cord and placental stem cells received after easy human delivery are used. The mesenchymal stem cells are introduced retrobulbarly in saline solution 1-2 ml containing 0.075-0.20×106 cell/kg. The cells are introduced 1-2 times annually.
EFFECT: method provides the effective treatment of corneal diseases in dogs by creating the depot stem cells in a close proximity to the lesion.
SUBSTANCE: invention relates to medical equipment, in particular to implanted devices for electrostimulation of auditory nerve, which include removable magnet. Implanted device 501 for electrostimulation of auditory nerve contains spherical internal holding magnet 502 and implanted unit of coil of receiver 504, which contains unit of fixation 503 of magnet with said magnet inside and is installed with possibility of changing magnet orientation with change of external magnetic field direction, as well as with possibility of removal and re-introduction of magnet into said unit.
EFFECT: application of invention will make it possible to reduce torque of internal magnet and ensure simple removal and introduction of internal magnet.
9 cl, 7 dwg
SUBSTANCE: invention relates to medicine, namely to ophthalmology, and can be used for treatment of "dry" form of age-related macular degeneration. For this purpose at preliminary stage, magnetic implant in form of flat rectangular plate is implanted intrasclerally in projection of macular area. 2 weeks after that, mesenchymal stem cells (MSC) of patient's own bone marrow, labelled with magnetic microparticles, are introduced to patient intravenously during 30-40 minutes. 2 hours before MSC introduction macular area of retina is irradiated by low-intensive laser irradiation with wavelength 632-633 nm, voltage 10 mW, diameter of laser irradiation spot is 4 mm, total time of irradiation is 5 minutes.
EFFECT: invention ensures targeted delivery of MSC to pathological nidus and retaining said cells for the time, required for efficient improvement of microcirculation and trophism of tissues, which contributes to steady stabilisation of visual functions.
SUBSTANCE: flat plate magnets of surface magnetic induction 300 to 360 mtl and maximum magnetic product "BH" of a material of the magnets not less than 255 kJ/m3 are introduced in afferent and efferent intestinal loop. The intestine is sutured end-to-end and embedded in an abdominal cavity.
EFFECT: method allows to prevent necrosis boundaries change from the values required.
3 ex, 2 dwg
SUBSTANCE: experimental thermochemotherapy treatment of tumours is ensured with introduction of magnetic antineoplastic preparation solution containing cytostatic agents. Then preparation is concentrated in tumour by exposure of inhomogeneous constant magnetic field followed by induction heating of tumour in variable magnetic field. After that tumour temperature is kept at +47 - +70°C. Then sphacelous tissues are removed using antiseptic solution. Cytostatic agents are introduced into metastasises.
EFFECT: higher life span in mammals, tumour debulking ensured with tumour tissue heating to such temperature at which cytostatic agents contained in magnetic preparation are activated thus invoking destruction of malignant membranes regardless of cell cycle phase.
4 tbl, 4 ex
FIELD: medical equipment.
SUBSTANCE: device with combined simultaneous magneto-hyperthermia exposure, generated by one applicator, is used in therapy for inflammatory processes. Device for intracavitary physiotherapy consists of dielectric casing with space for inner tube placing, cylindrical cores of ferrite material, divided by non-magnetoconductivity components, and electric heater in form of control winding, connected with current lead component. Cores and non-magnetoconductivity components are placed in inner tube space; control winding is located directly on inner tube surface and uniformly arranged along its active part.
EFFECT: therapeutic efficiency increasing, treatment period reducing, significant procedure facilitating.
2 cl, 1 dwg
SUBSTANCE: invention relates to medicine, namely to psychiatry, and concerns treating schizophrenia. That is ensured by administering a composite solution of cytokines which is prepared by arteriovenous perfusion of porcine spleen by physiological saline at a flow rate of 30-40 ml/min followed by sterilisation filtration and cryo-preservation. The cytokine solution is administered by inhalations in the form of a fine aerosol by a nebuliser in a dose of 10 ml/administration. Depending on the patient's initial state and the distinctions/severity of the disease for the first 3-5 days, the preparation is administered every 8 hours, then for 5-10 days - 1-2 times a day with a frequency of administration to be reduced to 1 time/3 days for 3 months with underlying total withdrawal of psychotropic agents.
EFFECT: administration of the cytokine solution which has a pronounced immunomodulatory effect in the developed regimen enhances the clinical effectiveness in the schizophrenic patients that manifests itself in the form of a pronounced reduction of the psychopathology by the scale PANSS and an induction of sustained remission lasting more than 6 months.
1 ex, 2 tbl