RU2119316C1 - Method for treating hemorrhage into eye internal media and sclera and retina - Google Patents

Abstract

FIELD: ophthalmology; may be used in treatment of hemorrhages into eye internal media and sclera and RETINA. SUBSTANCE: method includes adding adenosine-triphosphoric acid into autoplasma in gradually increasing concentration; determination of its amount sufficient for maximum aggregation of thrombocytes; introduction of it in the same volume of intact autoplasma and parabular introduction of produced supernatant fluid in the amount of 0.3-0.5 ml. EFFECT: higher efficiency of treatment and elimination of allergic reaction. 1 tbl

Description

 The present invention relates to the field of medicine - ophthalmology and is intended for the treatment of hemorrhages of various origins in the internal environment and the shell of the eye. Currently, in the treatment of diseases accompanied by hemorrhages (retinal vein thrombosis, diabetic retinopathy, non-traumatic hemophthalmus, etc.), thrombolytic therapy (plasminogen, streptodecase and their combination) is widely used (Nikolskaya V.V. Pathogenesis, clinic and treatment of hypertensive venous thrombosis retina, M., 1986, p. 195 (dis. MD); Ovayda D. Optimal medical and surgical methods for the treatment of hemophthalmia of non-traumatic genesis, M., 1992, p. 14 (dis. .n.).

 A disadvantage of the above therapy, a number of authors consider its low effectiveness and high allergenicity (Nikolskaya V.V. Pathogenesis, clinic and treatment of hypertensive venous thrombosis of the retina, M., p.194; Oosterhuis IA Die medikamentose Therapie des Venenvershlusses in der Retina - Bucherei des Augennarzres - 1983, Bd. 85. - S. 29-42).

 Recently, streptodecase has been widely used in hemorrhages of various localization (Katsnelson L.A., Gurtovaya E.E., Nikolskaya V.V. et al. Streptodecase in the treatment of retinal vein thrombi. 1993, No. 5, p. 60-62, "Bulletin of Ophthalmology"; Pisarenko SL The use of streptodease in thrombosis of the central retinal vein. - IV All-Russian Congress of Ophthalmologists. M., 1982, p. 421-422; Khamidova MK, Arkhangelskaya EP, Umarova A. A. // Thesis doc.configuration "fundus Pathology", M., 1986, p. 54-55; Chazov E.I., Smirnov V.P., Suvorova L.A. et al. Influence of the new domestic etc the drug "Streptodecase" on the fibrinolysis system. Cardiology, 1981, N 7).

 The therapeutic effect of streptodecase is due to the fact that it has a pronounced thrombolytic activity associated with its high ability to convert blood plasminogen into plasmin and inactivate its inhibitors. However, as said, this drug has a high allergenicity, which is explained by the fact that its active substance is streptokinase, that is, the vital product of B-hemological streptococcus. It is well known that almost every person carries infections caused by this most widespread microorganism. In addition, the existence of most foci of chronic infection (otitis media, tonsillitis, pyelonephritis, rheumatism, etc.) is also etiologically associated with B-hemolytic streptococcus. In this regard, each person has a different titer of antibodies to streptodecase and the higher it is, the greater the allergic reaction can be expected from the use of streptodecase. Therefore, all this sharply limits the use of streptodecase in the treatment of hemorrhage.

 The objective of the proposed method is to increase the effectiveness of the treatment of hemorrhages in the internal environment and the shell of the eye and eliminate the allergic reaction with this method of treatment.

At present, it is considered proven that in order to resorb hemorrhage, a high content of plasminogen and its activators is necessary (Gaffney P.J. Fibrinolysis. Modern fundamental and clinical concepts. M., Medicine, 1982, 240 pp.)
It is widely known that the conversion of plasminogen to plasmin is carried out under the action of plasminogen activators. The latter, that is, plasminogen activators, are divided according to the mechanism of action into three groups:
1) substances that activate plasminogen directly and specifically; urokinase, plasma and tissue activator;
2) substances that first convert an inactive proactivator into an activator, which then acts on plasminogen; streptokinase, tissue lysokinase;
3) proteolytic enzymes that break down peptide bonds in plasminogen into trypsin and plasmin (Andreenko G.V. Methods for the study of the blood fibrinolytic system. M., Publishing House of Moscow University, 1981, 40 pp .; Andreenko G.V. // Fibrinolysis (biochemistry, physiology, pathology - M., Medicine, 1979, 352 pp .; Uimen B. Biochemistry of the conversion of plasminogen to plasmin // Fibrinolysis. M., Medicine, 1982, pp. 28-37; N. Aoki, Aoki Na, M. Mokoi , J. Sakata // I. Clin. Invest. - 1978, vol. 61, p. 1186-1195).

 In solving the above problem, we drew attention to the fact that platelets, and not the blood coagulation system, play a leading role in the primary arrest of bleeding from microvessels, which are most vulnerable to vascular diseases of the eyes and most often become a source of hemorrhages. It is also known that platelets, to a much greater extent than blood coagulation, play an important role in maintaining normal resistance and function of blood vessels. Platelets to maintain and perform their basic functions contain more than five dozen biologically active substances, including serotonin, adrenaline, B-plasmin, taurine, TF, ADP, fibronectin, etc. (Kuznik B.I., Skipetrov V.P. Formed blood elements: vascular wall hemostasis and thrombosis. M., 1974, S. 307; Barkagan ZS. Hemorrhagic diseases and syndromes. M., 1980, S. 42-81; B. I. Kuznik, Vasiliev R. B. Immunogenesis, hemostasis and nonspecific resistance of an organism. M., Medicine, 1989, pp. 40-55). All these substances are located in platelets separately in dense granules - granules and lysosomes. It is noteworthy that platelets carry biologically active substances of diametrically opposite effects, for example, activators and inhibitors of the fibrinolytic system. Therefore, it is difficult to imagine that in the process of irreversible platelet aggregation, when the release of biologically active substances and the formation of a platelet plug occur simultaneously, so that the latter retains the equilibrium content of activators and inhibitors of the fibrinolytic system. In this case, platelets were unlikely to realize their physiological function in closing the defect in the vessel. Based on this consideration, the main postulate in obtaining a plasma drug with fibrinolytic and resorptive action was that inhibition of fibrinolysis predominates in a platelet plug, whereas substances of the opposite action, when a platelet clot (thrombus) is formed, are released by platelets into the plasma and blood. Therefore, by launching the mechanism of irreversible platelet aggregation (in vitrum) followed by their removal, we obtained plasma, a self-preparation with fibrinolytic and resorptive action.

Our studies have shown that with the proposed method for the treatment of hemorrhages in the internal environment and the eye shell with the administered parabulbar autopreparation, the plasminogen concentration significantly increases (P ≤ 0.01), the concentration of proteolytic enzyme inhibitors (α ₁ inhibitors) decreases (P ≤ 0.01) protease, α ₂ -macroglobulin, decreases (P ≤ 0.01) the concentration of fibrinogen and fibronectin while increasing plasma fibrinolytic activity (P ≤ 0.01), (see table). lei are well-known (Kalashnikov V.V., Markova O.A., Platonova T.K., Svishchev A.V. // Abstracts of the international symposium "Problems of development of work on laboratory diagnostic equipment", VNMTO MH USSR, Smolensk, 1988. - C. 41-44 and p. 47-50; Andreenko G.V., Karabasova M.A., Lyutova L.V. et al. "Methods for the study of the fibrinolytic blood system. - M., Publishing House of Moscow University, 1981, p. 43 - 46, Manchini G., Vaerman IP, Carbonara AO, Heremans IF A single-radial-diffusion method for the immunological quantitation of proteins, in Peeters H. (Ed.), Protides of the Biological Fluids, Elsevier Publisching Comp . Amsterdam, London, New Jork, 1964; 11th Collogium, Brudes, 1963, pp. 370-373). An increase in the fibrinolytic activity of autoplasma - the drug was achieved only under the condition of simultaneous administration of ATP, necessary for the maximum aggregation of autothrombocytes. The results of these studies served as a prerequisite for the proposed method of treatment. The effect of the obtained drug on hemo-, plasmoraggia, and conjunctival edema in rabbits on the model of conjunctival vascular thrombosis (according to V.V. Nikol'skaya) when it was administered parabulbarly in 0.3 ml daily showed that complete resorption of edema, hemo-, plasma, and hemorrhage occurred at 4 -6 days, while the same effect was achieved on days 21-25 and 18-22 in the control (without treatment) group and groups of animals receiving intact plasma, respectively.

 The method is as follows.

Blood is taken from a vein, usually ulnar, in an amount of 10.0 ml with a syringe with a capacity of 10.0 ml, in which there is an anticoagulant - heparin in an amount of 34 PIECES. Platelet aggregation is then determined according to the known method of Born-O'Brien (Born VR Aggregation of blood plateletes by adenosine diphospate and its reversal ". Nature, 1962, vol. 194, p. 927-939), but using adenosine triphosphoric acid as an aggregate (ATP). It is known that ATP is not an aggregate and therefore was never used in clinical practice in this quantity, however, back in 1965, L. Marr showed that in plasma, after only a few seconds, 50% of ATP is converted to ADP (Z.S. Barkagan, "Hemorrhagic diseases and syndromes", M., 1980, pp. 12-13). ATP was used in an amount of 0.1-0.5 mg / ml depending on the individual reaction of platelets to ATP exposure to achieve maximum platelet aggregation (an average of 50% decrease in platelet optical density) .This determines the choice of the required amount of ATP. Moreover, first we add ATP in increasing doses, gradually, which goes away from 1 to 5 minutes With this method of administering ATP, the firbinolytic activity and concentration of proteolytic enzyme inhibitors, namely (α ₁ protease inhibitor, α ₂ macroglobulin) in autoplasma does not change by comparison intact plasma. With this method of administering ATP, we determine only the amount needed to maximize the drop in the optical density of autoplasma. Then, the found amount of ATP is introduced simultaneously into the same volume of intact autoplasma. A suspension is obtained, it is centered at 3000 rpm for 2-3 minutes. And the supernatant thus obtained is injected parabulbarly in an amount of 0.3-0.5 ml.

 Example 1. Patient M.T.V., 66 years old.

 Diagnosis: right eye - beg. cataract.

 The left eye is an involutional central chorioretinal dystrophy (exudative-hemorrhagic form). The proposed method was used to treat the left eye.

 The state of the left eye before treatment: visual acuity of 0.2, is not corrected. On the fundus in the paramacular region - an oval form of hemorrhage in the retina, in the macular region - pronounced edema of the retina.

 Treatment: blood was taken from the ulnar vein in an amount of 10.0 ml with a sterile 10 ml syringe, in which heparin was 34 units before blood collection. Red blood cells were separated in the usual way. The resulting plasma was divided into two equal portions of 2.0 ml. In the first, platelet aggregation was determined (according to the above method), gradually adding ATP, starting from 0.1 mg / ml. The maximum platelet aggregation was achieved with a total administration of ATP of 0.3 mg / ml, which took 4 minutes. The same amount of ATP, i.e. 0.3 mg / ml, was simultaneously injected into the second portion of intact plasma, the maximum platelet aggregation was achieved within 1 minute. Then it was centrifuged at a speed of 3000 rpm and the supernatant thus obtained (autoplasma - preparation) was introduced parabulbarly to the left in the lower temporal region in an amount of 0.3 ml once a day. In the following days, the supernatant was obtained as described above, but without preliminary determination of the total ATP and the same amount was administered parabulbarly, 10 injections were required for the course of treatment. The injections were carried out according to the following scheme: two days in a row - once a day, after one day of a break - again 1 time per day for two days, then an interval for two days and a repeat of the indicated cycle next week and so on up to 10 injections.

 Treatment results.

 The visual acuity of the left eye is 0.6, is not corrected. Positive dynamics on the fundus - hemorrhages were almost completely resorbed and edema in the central zone of the retina was reduced.

 Example 2. Patient S.O.S., 49 years old.

 The diagnosis is preproliferative diabetic retinopathy in both eyes.

 Eye condition before treatment: Visual acuity of the right eye - 0.4. Visual acuity of the left eye is 0.5. At the bottom of both eyes on the periphery and in the paramacular region of the retina is round in shape, of various sizes and limitations of hemorrhage, in the macular region - retinal edema.

 The treatment was carried out in both eyes. Autoplasma - the preparation was technologically prepared in the same way as in example 1. The preparation of the preparation required 0.5 mg / ml ATP. The drug was administered parabulbarly on both sides 10 times according to the same scheme as in example 1.

 Treatment results.

 Visual acuity of the right eye - 0.8; visual acuity of the left eye - 0.8.

 At the bottom of both eyes, retinal hemorrhages in the center almost completely resolved, hemorrhages on the periphery of the fundus of the eye were partially resorbed, retinal edema decreased in the paramacular region.

 In total, the proposed method treated 16 patients with different localization of hemorrhage in the internal environment and the shell of the eye. Marked clinical effect was confirmed by clinical and laboratory research methods and long-term follow-up after treatment for 12 months.

Claims (1)

 A method for the treatment of hemorrhages in the internal environment and the eye shell by parabulbar administration of fibrinolytics, characterized in that adenositriphosphoric acid is added to the autoplasm in a gradually increasing concentration, its amount is sufficient for maximum platelet aggregation, and it is added to the same volume of intact autoplasma, and a supernatant is obtained liquid and inject it in an amount of 0.3 - 0.5 ml.

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