Method of slowing down rough scarring of conjunctiva

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to ophthalmology and is intended for slowing down rough scarring of conjunctiva in carrying out photodynamic therapy in conditions of vascular proliferation of conjunctiva. First, not less than 2 mg of alasense are introduced subconjunctivally. After 1.5-2 hours impact with laser radiation with wavelength 632.8 nm, power density 47.7-55.7 mW/cm2, is performed for 10-14 minutes. 12-24 hours after intervention medication viscleron is introduced into conjunctival sac of affected eye 1 drop 3 times per day, during not fewer than 10 days.

EFFECT: method ensures efficient suppression of angiogenesis of conjunctiva vessels in zones of proliferating cells due to application of aggressive parameters of laser impact with simultaneous prevention of necrobiotic and destructive changes due to protective effect on irradiated tissues.

2 ex

 

The invention relates to medicine, namely to ophthalmology, and is intended for braking rough scarring of the conjunctiva.

The use of photodynamic therapy (PDT) in ophthalmology includes intraocular tumors, subretinal neovascular membrane, ablation of the ciliary body (Rivelles M.J., 2000), and the result of therapy is the occlusion of newly formed vessels with preservation of surrounding tissue (Graefes Arch Clin Exp Ophthalmol. - 2002. - Vol.240. - P.749-757).

Andreyev YU.V. (1993) suggested the use of PDT with the aim of destruction of newly formed vessels in the cornea in the experiment.

The analogue of the present invention is a method of the same purposes, representing PDT Radachlorin®, consisting of three cyclic tetrapyrroles chlorin nature (gidrirovanny ring D), the main of which (80-90%) - chlorin E6 used to have plastic surgery conjunctival filtration pillows after antiglaucomatous operations (Prokofiev M.I. // Diss. Kida. the honey. Sciences. Laser correction function of filtering blebs after fistulizing antiglaucomatous surgery. - Moscow. - 2004). The method includes subconjunctival introduction 0.3 ml of Radachlorin in the area of cystic filtration bags (CFP), representing a zone of proliferation and neovascularization. Next put coagulate argon laser with a wavelength of 488,5-511 nm in random order on the entire surface of the pads from the periphery to the center. The radiation power is 0.5 W, exposure time of 0.2 sec, the diameter of the focal spot of 50-100 μm, the number coagulates 40-60. When this happens zapustevanie newly formed vessels and their destruction.

The disadvantages of the method are the development of necrobiotic changes in the deeper layers of the conjunctiva with subsequent increased proliferation of fibroblasts in the impact zone, in the surface layers actually conjunctiva develops vasoproliferative activity, appear locally destructive lesions, formed parts of the seal. There is also the need to use a separate product for identifying and clarifying boundaries proliferation when performing fluorescent diagnostics.

The closest solution to the proposed method is conducting photodynamic therapy, including introduction to subtenons space of 0.5-1.0 ml of albenza obtained by dissolving 2 mg of the drug in 10.0 ml of saline solution, and oral administration of 4 mg/kg (8 mg) of albenza in breeding saline solution to 2.0 ml of the Subsequent contact of the irradiation zone of proliferating cells by laser with a wavelength of 632.8 nm, power of 50-60 mW and a beam diameter on the end of the fiber 2-4 mm Exposure time steps 10-14 minutes (see the Study of the impact of Albenza on connective tissue and newly formed vessels fresh scar the situation on the willow / Balashova L.M., Popov A.V., Kuzmin YEAR, Shevchik S.A., Spivak IA // Clinical gerontology. - 2006. - Vol.12, No. 9. - S).

However, using the proposed parameters PDT leads to insufficient intravascular thrombosis, and increase the power and duration of radiation - excessive effect that can even stimulate the processes of excessive proliferation of fibroblasts in the impact zone, vasoproliferative activity and form parts of the seal. The need for oral administration of the drug in parallel with local makes the technique is inconvenient, especially considering that alasens has a strong unpleasant salty taste, which is not easy to get rid of, because the connection with the change of the pH value becomes unstable.

Attention of modern researchers is to find new methods to achieve inhibition of angiogenesis vessels of the conjunctiva in zones of proliferating cells and to prevent rough scarring of the conjunctiva, necrobiotic and destructive tissue changes.

The task of the invention is to develop a method that would preclude rough scarring of the conjunctiva, caused inhibition of angiogenesis vessels of the conjunctiva in zones of proliferating cells and did not cause necrobiotic and destructive changes in tissues, would have minimal toxic is esteem and simultaneously served as a reliable marker zones of proliferating cells.

Method of braking rough scarring of the conjunctiva includes photodynamic therapy, in which first imposed subkonyunktivalno at least 2 mg of alasens, and then after 1.5-2 hours exposed to laser radiation with a wavelength of 632.8 nm.

The method differs in that the influence of the laser radiation power density 47,7 and 55.7 mW/cm2should be performed within 10-14 minutes, and within 12-24 hours after the intervention in the conjunctival SAC of the affected eye impose drug villeron 1 drop 3 times a day, for at least 10 days.

The technical result of the proposed method is the inhibition of angiogenesis vessels of the conjunctiva in zones of proliferating cells in the absence of necrobiotic and destructive changes in the tissue.

The invention consists in the following.

Method of braking rough scarring of the conjunctiva involves performing photodynamic therapy with the introduction of regulatory polypeptide, acting as the protector of irradiated tissues. First, 0.05 g of albenza dissolved in 10 ml of saline and injected the resulting solution subkonyunktivalno at a dose of not more than 1.0 ml in 1.5-2 hours conducting contact exposure to laser radiation for 10-14 minutes. The wavelength of 632.8 nm, power density 47,7 and 55.7 mW/cm2. Within 12-24 hours after exposure to spend me what the things the introduction of regulatory polypeptide for at least 10 days. In the particular case as a regulatory polypeptide can be used solution Villeroy. The dosage may be one drop 3 times a day.

The method is as follows.

First alasens representing the drug on the basis of the hydrochloride of 5-aminolevulinic acid in powder form, dissolved in physiological solution in an amount of not less than 0.05 g per 10 ml. Next subkonyunktivalno in the area of the resulting scar impose no more than 1.0 ml of the obtained solution. If necessary, conduct registration zones of proliferation. After 1.5-2 hours to carry out contact action on a zone of fresh rumen helium-neon laser radiation for 10-14 minutes. The wavelength of 632.8 nm, power density 47,7 and 55.7 mW/cm2. As the radiation source can be used in the apparatus of LESA-01 "BIOSPEC". Within 12-24 hours after exposure to carry out the local introduction of regulatory polypeptide for at least 10 days. In the particular case as a regulatory polypeptide used winklern, which is used by instillation of a solution. The dosage may be at least one drops 3 times a day.

The drug Villeron" 5 ml (eye drops) issued by the company LLC "SIV-PHARM" (http://www.vio-farm.ru.) represents a complex of natural non-protein low-molecular regulatory peptides non-hormonal of origin Taiwan is born, obtained from the sclera of the eyes of animals. Contains the active substance in 1 ml with the concentration of peptide is 10-10mg/ml Pharmacological activity of the drug is determined by the content of low molecular weight peptides exerting regulatory effects on the homeostasis of the sclera of the eye, has a regulatory influence on the biochemical and morphological properties of the sclera of the eye. In addition, it is known that under the action of the drug Villeron due to the protective properties of the observed increase in the viability of the fibroblasts, which are involved in the synthesis of collagen and other molecules of the extracellular matrix, and actively share with tissue damage compared with the control group (Kachalina AV, Krasnov MS to study the regulatory protein isolated from the sclera of the eye of the bull // proceedings of V all-Russian scientific seminar and Youth scientific school "Chemistry and medicine": "New drugs: progress and prospects", Ufa: Gil, 2005, p.116; Skripnikova B.C., Kachalina AV, Krasnov, MS, Yamskov VP, Yamskov I.A. investigation of the regulatory protein, isolated from the sclera of the eye of the bull // proceedings of the VI annual international youth conference IBCP RAS-vuzes, Moscow, 24-27 November, 2006, s-224).

The invention is illustrated by the following examples.

Example 1.

Experiments which was held on 6 rabbits of the chinchilla breed, which was received adequate model of vascular proliferation of the connective tissue in the condition of the wound healing process. To do this, after sedation and analgesia using microsurgical instruments produced by the conjunctival wound in the upper part of an eye of a length of 0.5 cm 1.5-2.0 mm from the limbus and parallel to it.

After five days all the rabbits in the right eye with overgrown wound conjunctiva and a large number of newly formed vessels in the field of tender scar under the conjunctiva was injected with 1.0 ml of drug alasens (in breeding 0.04 g in 10 ml of saline). Then through 1,2-2,0 h for 14 min spent the contact area irradiation scar laser with a wavelength of 632.8 nm, power density 47,7 and 55.7 mW/cm2. The left eye remained in control.

On the next day after PDT in the experimental eyes were buried officinal solution of Villeroy 3 times a day for 10 days.

Clinically, when viewed in the slit lamp after the introduction of alasens and subsequent laser exposure experienced in the right eye was determined by sudden blanching of the scar and the narrowing of blood vessels of the conjunctiva. The morphological examination three days after exposure in the right eyes in the damaged region of the epithelium was absent for a considerable extent due to its detachment from the underlying loose connective tissue. In adjacent to the handicapped is the area of the epithelium consisted of three or four or more layers of undifferentiated, hypertrophied epithelial cells, showed the fragility of the epithelial-stromal relationships. Loose fibrous connective tissue significantly swollen and necrotization. This was manifested in the form of a plurality destroyed, non-nuclear neutrophilic leukocytes and granulation of the fibrous structures of the intercellular substance. The tissue was attended by a small number of fibroblastic cells of the row. In konyunktivalny region a large number of large desolate and small newly formed vessels with shaped elements in the lumen in the area close to the damage. In the control left eyes defined the formation of loose fibrous connective tissue, covered with three or four layers of the epithelium, with a large number of newly formed vessels and fibroblast cells of the row.

In the study through ten (conjunctival area in ten days, experience: the newly formed vessels in the damaged area of the epithelium is not fully restored, the expansion of the lumen of the vessels of the venous bed; conjunctival area in ten days, monitoring: the newly formed blood vessels, minor leukocyte infiltration) and thirty days (conjunctival area thirty days, experience: minor bleeding, most likely associated with the violation of the integrity with the address, swelling of the cells forming the wall of the newly formed vessel; conjunctival area thirty days, control: vessels of normal diameter, a slight swelling of loose fibrous connective tissue, saved multilayered epithelium) significant differences between experimental and control eyes were not found.

Thus, in the experimental eyes was attended by signs indicating the presence of adequate intravascular thrombosis (extension of the lumen of the vessels of the venous bed in 10 days) with confirmed morphologically significantly less content in the tissue cells (fibroblasts), characteristic of the formation of unsightly scars. In the control eyes was determined by a large number of fibroblasts, which indicates the formation of rough scar.

Example 2.

The method was carried out according to the method prototype

After receiving an adequate model of vascular proliferation presented in example 1, method five days all the rabbits in the right eye with overgrown wound conjunctiva and a large number of newly formed vessels entered and 1.0 ml of alasens under the conjunctiva in the area of the scar and oral 4 mg/kg (8 mg) of albenza in breeding saline solution to 2.0 ml Then through 1,2-2,0 h for 10 min was carried out the irradiation zone scar laser with a wavelength of 632.8 nm, 60 mW, dia is the ETP of the beam at the end of the fiber 4 mm Left eye remained in control.

Produced clinical observation, measurement, accumulation in the tissues of the eye of protoporphyrin IX in time and morphological studies.

Clinically immediately after the procedure when viewed through a slit lamp noted similar changes of the conjunctiva described in example 1. The morphological examination three days after exposure in the right eyes in the damaged region of the epithelium were also absent. In konyunktivalny region revealed a large number of large desolate vessels. In the control left eyes defined the formation of loose fibrous connective tissue, covered with three or four layers of the epithelium, with a large number of newly formed vessels and cells of fibroblastic series. In all cases received a large amount of coarse fibrous connective tissue 10-30 day in combination with desolate vessels, which indicates insufficient intravascular thrombosis.

Thus, the proposed method is a simple method of procedure PDT inducing intravascular thrombosis in zones of proliferating cells to adequately prevent the development of rough scar through the use of aggressive parameters of laser exposure, combined with the introduction of the PE estomago polypeptide, acting as the protector of irradiated tissues.

Method of braking rough scarring of the conjunctiva, including photodynamic therapy, in which first imposed subkonyunktivalno at least 2 mg of alasens, and then after 1.5-2 h influence of laser radiation of wavelength 632.8 nm, characterized in that the influence of the laser radiation power density 47,7 and 55.7 mW/cm2should be performed within 10-14, and 12-24 h after surgery in the conjunctival SAC of the affected eye impose drug villeron 1 drop 3 times a day, for at least 10 days.



 

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