RU2129875C1 - Method for treating viral genesis pathology of neck of the uterus - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: method involves locally administering endogenous autocytokin complex at a dose of 3 ml having 150-200 mcg/ml concentration of protein daily in the course of 5 procedures after performing laser destruction of changed sites. EFFECT: accelerated process of crust rejection.

Description

 The invention relates to medicine, in particular to obstetrics and gynecology, and can be used in a clinic for the treatment of patients with cervical pathology of viral etiology in combination with laser destruction.

One of the generally accepted methods for treating cervical pathology of viral etiology is laser destruction of pathologically altered areas of the cervix by CO ₂ with a laser with an output power of 12-16 W, depth from 0.4 to 0.8 cm in combination with the subsequent administration of antiviral drugs, immunomodulators administered to the cervix in the form of tampons with 7 days of the postoperative period (Pinegin B.V., Minkina G.N., Manukhin I.P., Saprykina O. A. Effect of glucosaminylmuranyl dipeptide on the immune status and clinical condition of patients with affected eat cervical human papillomavirus Bulletin of Experimental Biology and Medicine 1.993 N 2. pp 168- 169)....; ozone therapy before and after destruction in the form of local applications for 7-14 days and intravenous drip of ozonized physiological saline from 3 to 8 times (Dzhibladze M.A. Comprehensive treatment of candidiasis in women using laser radiation and ozone therapy. - Abstract. on competition for the degree of candidate of medical sciences.-1994).

 The disadvantages of these methods are prolonged epithelization of the wound surface, the use of pharmacological drugs with side effects, low efficiency, relapse occurs in 10-14.3% of cases.

 The essence of the method for the treatment of cervical pathology of viral etiology is that a patient after laser destruction of pathologically altered areas, a tampon with a complex of endogenous cytokines in the amount of 3 ml with a protein concentration of 150-200 μg / ml for 6 hours is delivered to the cervix. A swab with a complex of endogenous cytokines is repeated after scab rejection for 6 hours daily in a course of 5 procedures.

 A complex of endogenous cytokines was obtained as a result of in vitro stimulation of peripheral blood mononuclear cells by phytohemagglutinin. The therapeutic effect is due to the combined effect of a combination of natural polyptides in optimal concentrations and ratios (interleukin 1, interleukin 2, interleukin 6, tumor necrosis factor).

 Cytokines perform a dual function. On the one hand, they activate neutrophilic white blood cells and macrophages at the site of their exposure, initiate blood cell migration, stimulate oxygen metabolism and phagocytic activity, which accelerates the elimination of infection and the onset of the regeneration phase. On the other hand, cytokines trigger a local cytokine cascade. The above effects of the complex of endogenous cytokines in combination with laser destruction of pathologically altered parts of the cervix determines the clinical effect in patients with viral lesions.

 The tampon is a gauze ball with a diameter of about 1.5 centimeters, impregnated with a complex of endogenous cytokines.

 The volume of the complex of endogenous cytokines of 3 ml was chosen because it is precisely this amount of fluid that is necessary and sufficient for one cervical treatment procedure.

 The course duration of 6 procedures (1 - immediately after laser destruction and 5 after scab rejection) was chosen because by 8 days there is a complete closure of the wound surface with stratified squamous epithelium.

The method is as follows. 2 days before the alleged laser destruction of the cervix, a complex of endogenous cytokines is prepared. Obtaining a complex of endogenous cytokines, which are the supernatant of an autologous culture of mononuclear cells, is carried out by the following method. A patient is sampled with 20 ml of venous blood from a cubital vein in a sterile silicone tube containing 0.5 ml of heparin (5000 units / ml). Mononuclear cells are isolated from the obtained blood by centrifugation on a Ficoll-Verographin density gradient. The isolated mononuclear cells are washed three times with Versen's solution, then a suspension of cells with a concentration of 5 · 10 ⁶ / ml is prepared in medium 199 containing gentamicin (80 μg / ml). To the resulting suspension of mononuclear cells add phytohemagglutinin at a rate of 20 μg / ml, incubate for 3 hours in an incubator at a temperature of 37 ^o C. Thoroughly wash the cell suspension with Versen solution, add medium 199 to the initial volume and incubate for 20 hours at a temperature of 37 ^o C. A suspension of mononuclear cells is centrifuged for 10 minutes at a speed of 1500 rpm. The resulting supernatants are filtered through sterile synpore or millipore 0.22 filters. The biological activity of supernatants is assessed in a neutrophil phagocytic activity test. The amount of total protein in the supernatant is determined by Lowry spectrophotometric method. The supernatant containing the complex of endogenous cytokines is packaged in sterile vials and stored in the freezer compartment of the refrigerator at a temperature of minus 20 ^o C.

On the 5-7th day of the menstrual cycle, the patient undergoes laser destruction of the pathologically altered cervix with a CO ₂ laser at an output power of 12 W, with a depth of 0.4 to 0.8 cm, depending on the degree of damage, after which a tampon with a complex is applied to the cervix endogenous cytokines in an amount of 3 ml with a protein concentration of 150-200 μg / ml for 6 hours. A tampon with a complex of endogenous cytokines is repeated after scab rejection, that is, for 3-4 days for 6 hours daily with a course of 5 procedures.

 Example. Patient S., 20 years old, was registered in the antenatal clinic at the 1st clinical hospital in Smolensk since 2.03.95 when cervical erosion was detected during examination by a gynecologist. From the anamnesis: Menstruation from 14 years to 7 days, after 30-32 days, moderate, painless. There were no births, no abortions. Sex life from 18 years, regular.

 Of the diseases noted frequent SARS.

 When a vaginal examination revealed erosion of the cervix.

 Test results: RW, HIV - negative. General blood test: Er-4.43 • 10 g / l, HB 137 g / l, C. P-0.93, L 5.8 • 10 g / l, E-1, P-4, S-65 , L-27, M-3. Smears from the vagina: chlamydia, gardnerela not found, the flora corresponds to 2 degrees of purity of the vaginal smear. Sowing from the vagina - no growth.

 Extended colposcopy: cervical candidiasis, papillary puncture, signs of a viral lesion of the cervix. Biopsy taken.

 November 28, 1995. The patient was taken blood to isolate a complex of endogenous cytokines. Prepared 6 servings of the drug.

November 30, 1995. Laser destruction of a pathologically altered cervix by a CO ₂ laser was performed at a laser output of 12 W, a depth of 0.8 cm in the cervical canal. After that, a tampon with a complex of endogenous cytokines of 3 ml was delivered to the cervix protein concentration of 150-200 μg / ml for 6 hours. Scab rejection was noted on day 4, at the same time, active marginal epithelization was observed. After scab rejection, a swab with a complex of endogenous cytokines was again applied to the cervix for 6 hours daily with a course of 5 procedures. On the 8th day after laser destruction, a "closure" of the wound surface with a thinned stratified squamous epithelium was noted. Complete epithelization occurred on day 16.

 With extended colposcopy after 1 month 22 days: the entire ectocervix is covered with stratified squamous epithelium.

 A total of 57 patients with cervical lesions of viral etiology were examined and treated. The control group consisted of 25 women, the main component of the treatment of which were laser destruction of the cervix and traditional antiviral therapy. The main group consisted of 32 patients who, along with laser destruction of the cervix, used tampons with a complex of endogenous cytokines isolated from the peripheral blood of the patient herself.

 The age of the patients of the main and control groups ranged from 20 to 46 years.

 With extended colposcopy, signs of atypical epidermis were noted: atypical epithelium with the structure of a mosaic, papillary mosaic, puncture.

 A histological examination revealed signs of para- and hyperkeratosis, lymphoid infiltration, coilocytosis, that is, data characteristic of a viral lesion.

For all patients on the 5-7th day of the menstrual cycle, laser destruction of the pathologically altered cervix was performed with a CO ₂ laser at an output power of 12 W, with a depth of 0.4 to 0.8 cm, depending on the degree of damage. After laser destruction, a tampon with a complex of endogenous cytokines in the amount of 3 ml with a protein concentration of 150-200 μg / ml for 6 hours was delivered to the patients of the main group after laser destruction. A tampon with a complex of endogenous cytokines was reapplied after scab rejection, that is, for 3-4 days for 6 hours daily with a course of 5 procedures.

 Monitoring the effectiveness of treatment was carried out on the basis of the following parameters: the time of scab rejection, the beginning and end of epithelization of the wound surface according to colposcopy and cytology, immunological, microbiological and histological research methods.

 When analyzing the results, it was noted that scab rejection in patients of the main group occurred on 3-4 days, at the same time active marginal epithelization was determined, complete epithelization occurred on 16-18, and with extensive lesions on 21-22 days from the time of surgery. In the control group, scab rejection occurred at 6–7, and complete epithelization of the wound surface at 28–30 days.

 The study of the immune status was carried out in 15 patients of the main and 14 control groups. An immunodeficiency state was observed, manifested by a decrease in the total number of T-lymphocytes, an imbalance in the subpopulations of T-helpers and T-suppressors, and a decrease in the immunoregulatory index. Indicators of the humoral link of immunity and phagocytic activity of neutrophils remained within the age norm. After treatment, the main group of patients showed a tendency to increase the total number. T-lymphocytes with normalization of subpopulations of T-helpers and T-suppressors, increased phagocytic activity of neutrophils.

 A comprehensive examination after 1.5 months in patients of the main group of data for viral lesions of the cervix was not revealed. In the control group, 4 (16%) had a relapse of the disease.

 Thus, the studies have proven the high efficiency of local application of the complex of endogenous cytokines in the treatment of cervical pathology of viral etiology.

Using the proposed method for the treatment of cervical pathology of viral etiology provides the following advantages:
1. The time of scab rejection and the time of complete epithelization of the wound defect after laser destruction are reduced.

 2. Increases the effectiveness of treatment.

 3. The pharmacological and allergic load on the patient’s body is reduced, since a drug obtained from the patient herself is used.

Claims (1)

 A method for the treatment of cervical pathology of viral etiology, including laser destruction of pathologically altered areas of the cervix and topical use of the drug, characterized in that the complex of natural autocytokines isolated from the culture of the patient’s peripheral blood-stimulated phytohemagglutinin mononuclear cells is used as a drug, in an amount of 3 ml with a protein concentration of 150 - 200 μg / ml, applied locally immediately after laser destruction and after rejection of the jet PA daily course of 5 procedures.