RU2072866C1 - Method of endometritis treatment - Google Patents

Abstract

FIELD: medicine, obstetrics and gynecology. SUBSTANCE: method involves intrauterine administration of immosime at a single dose 200-1125 "ПЕ" at course 3-4 administrations in combination with the individual complex therapy. EFFECT: enhanced effectiveness of treatment.

Description

 The invention relates to medicine, mainly to obstetrics and gynecology, and can be used in the treatment of inflammatory diseases of the uterus, namely acute, subacute and exacerbations of chronic endometritis and metroendometritis.

 Issues of prevention and treatment of purulent-inflammatory diseases of the internal genital organs is one of the most pressing problems of obstetric and gynecological practice.

 Among various inflammatory diseases, endometritis is one of the common forms. According to domestic and foreign authors, its frequency in the postpartum period is 0.4-0.8% among the total number of puerperas and 6.3-40% among patients with postpartum inflammatory diseases. In the structure of infectious and inflammatory complications after artificial abortions, endometritis accounts for up to 30% of cases. Endometritis occurs in 12-16% of women who have terminated a pregnancy.

 The risk of infection with the introduction of IUDs is about 2-4%. At the same time, endometritis is a frequent complication of this type of concentration.

 One of the main causes of the occurrence of endometritis after childbirth, abortion, surgery is infection of the uterine cavity in the presence of residues of the fetal egg. Infection most often penetrates the uterus in an ascending way during childbirth, abortion, intrauterine intervention, in the postpartum or postabortion periods. However, even with bacterial contamination of the uterine cavity, endometritis does not always develop. The severity and duration of the disease is largely determined by the prevalence of the process, the nature of the lesion and the type of pathogen.

 When bacteria enter the blood serum and the remains of the fetal egg, the conditions of the so-called "thermostat" are created, which contributes to the rapid multiplication of microorganisms. The antibacterial therapy prescribed in these cases is not effective enough, since antibiotics from the blood do not enter the blood clots in the uterus and the remains of the ovum. Such therapy is designed primarily to prevent the spread of infection outside the uterus. The cessation of the infectious process is facilitated by the release of the uterus from infected and necrotic tissues.

 Known methods for local treatment of endometritis slightly differ from each other and consist in the mechanical or instrumental removal of infected residues of the fetal egg using antibacterial drugs during perfusion, washing or drainage of the uterine cavity / 1, 2 /.

 There is a method of treating postpartum endometritis with the domestic drug "Dioxol" containing dioxidine, methyluracil, trimecain and polyethylene glycol by introducing 3-10 ml of the drug into the uterine cavity after washing it with an antiseptic solution / 3 /. However, the constituent components of this drug do not have a direct effect aimed at cleansing the uterine cavity from purulent-inflammatory contents and tissue detritus. Duration of treatment is 8-12 days.

 A known method for the diagnosis and treatment of endometritis after childbirth with the help of hysteroscopy, which allows you to clarify the variant of endometritis, the presence of residual fetal eggs, wash the uterine cavity from blood clots. In this case, solutions of furatsilin 1: 5000 or 0.5% chlorhexidine in an amount of 1-1.5 liters are used. Diagnosed residues of the fetal egg are removed with subsequent careful curettage of the walls of the uterine cavity, which is a pathogenetically substantiated therapeutic measure / 4 /. However, a single washing of the uterine cavity is clearly not enough in the treatment of true endometritis, since subsequent removal of wound detritus is not ensured.

 Closest to the claimed prototype method is a method for the treatment of postpartum and postabortion endometritis by intrauterine infusion of a mixture of furatsilina, penicillin and bile acid / 5 /. According to the method of two or three irrigation of the uterine cavity with a mixture of 500 thousand units of 1 million units of penicillin, 4-10 ml of r-ra furatsilina 1: 5000 and deoxycholic acid in a dose of 0.5 g, followed by curettage of the uterine cavity is enough to treat endometritis. At the same time, the average hospital bed day was 8.7 days.

 Bile acid, having surface-active properties, increases the sensitivity of microorganisms to many antibiotics. However, the need for subsequent instrumental emptying of the uterine cavity does not allow us to consider this method quite gentle.

 The objective of the invention is to increase the effectiveness of the treatment of inflammatory diseases of the uterus by reducing its duration, providing a gentle effect on the endometrium.

 The stated technical problem is achieved by the fact that against the background of individual complex therapy, the patient is intrauterine injected with an immunozyme in a single dose of 200-1125 PE with a course of 3-4 injections.

Immozyme is a complex of bacterial proteinases "crosslinked" by the radiation-chemical method with a soluble carrier of polyethylene oxide (m. M. 1500). The drug is a colorless liquid without taste and odor, with a specific activity of 50-75 PE / ml. For the unit of activity, take such an amount of the drug that converts 1 mg of tyrosine into an acid-soluble fraction for 1 hour at 37 ^° C (casein is used as a substrate). The drug was approved by the Pharmacological Committee of the Ministry of Health of the USSR for clinical trials. Immozyme is obtained by the method described in A.S. USSR N 1442548.

 The proposed method of treatment is as follows: depending on the variant of endometritis, the immozyme is administered intrauterine in a single dose of 200-1125 PE (4-5 ml of the drug with an activity of 50-75 PE / ml, in the postpartum period, depending on the volume of the uterine cavity at different stages of involution from 8 to 15 mg). The drug is administered intrauterine using a Brown syringe or a Record syringe with an adapted uterine tip under aseptic conditions after treatment of the cervix with an antiseptic. To achieve a greater therapeutic effect, the patient maintains a horizontal position for 3-4 hours. 3-4 intrauterine instillations are enough for the course of treatment, depending on the nature and severity of the disease. Indications for the use of immozyme are acute, subacute and exacerbations of chronic endometritis and metroendometritis. The drug can be used to prevent endometritis in the postoperative period during operations on the uterus. Contraindication to the use of the immunozyme is the presence of moderate or heavy spotting, menstruation.

 In the clinic, the immozyme was used as an intrauterine instillation in the complex therapy of 57 patients suffering from various inflammatory diseases of the uterus. The drug was administered through a uterine tip adapted to a Record syringe in a single dose of 200-375 PE (4-5 ml) of the drug with an activity of 50-75 PE (ml) daily, for a course of 3-4 procedures. The disappearance of uterine pain, normalization of the nature of the discharge, positive dynamics of laboratory parameters, cytomorphological characteristics of aspirates from the uterine cavity and hysteroscopy data were observed in most cases after 3-fold administration. No adverse effects and complications were noted.

 Table 1 shows the dependence of the effectiveness of the treatment of inflammatory diseases of the uterus on the drugs used.

 From table 1 it is seen that the use of immozyme can increase the effectiveness of treatment of inflammatory diseases of the uterus and reduce the treatment time for patients by an average of 3-5 days.

 When using the proposed method, the joint use of the immunosym with broad-spectrum antibiotics and antiseptics is possible. In this case, the immunozyme retains its specific activity.

 The principal difference of the proposed method compared to the prototype is the use of a proteolytic enzyme-immozyme as a therapeutic agent for cleaning the uterine cavity in an experimentally selected optimal mode: a single dose for inflammatory diseases of the uterus 200-375 PE (4-5 ml of the drug with an activity of 50-75 PE / ml), in the postpartum period - 400-1125 PE (8-15 ml of the drug), the total dose per treatment course is 600-4500 PE (12-60 ml of the drug with an activity of 50-75 PE / ml), which reduces the treatment time for inflammatory diseases uterus on 3-5 days.

 The therapeutic effect of the immunozyme is due to the prolonged proteolytic and fibrinolytic effects of the drug. The introduction causes intensive hydrolysis of intrauterine purulent-inflammatory contents and non-viable tissues. Along with this, the immozyme also exhibits a new non-obvious property that absorbs hydrolysis products on itself, this contributes to a more effective cleansing of the uterine cavity. This property of the immunozyme is manifested due to the use of polyethylene oxide as a carrier during immobilization, which unexpectedly turned out to be an active sorbent of proteolysis products formed during the interaction of the enzyme with non-viable tissues. Such a double directed action, moreover, prolonged and not inherent in soluble proteolytic enzymes, allows to reduce the treatment time for inflammatory diseases of the uterus.

 Empirically, when using the drug in a clinic for the treatment of nonpartum endometritis, it was found that intrauterine administration of the drug in a single dose of 200-375 PE (4-5 ml of the drug) is accompanied on the first day by an increase in the amount of inflammatory discharge from the uterine cavity, which decreases and normalizes in nature after 3-4 injections. The use of the drug in a single dose of less than 200 PE does not have a reliable therapeutic effect. The introduction of immozyme in a single dose in excess of 400 PE, leads to an unjustified increase in the consumption of the drug with the appearance of undesirable side effects in the form of moderate spotting, which require additional hemostatic therapy for 1-3 days.

 Table 2 shows the dependence of the effectiveness of the treatment of inflammatory diseases of the uterus on the activity of the immunozyme.

 From table 2 it is seen that the optimal dose of the drug lies in the range of 200-375 PE / ml.

 Table 3 presents the exchange rate doses of immunozyme depending on the variant of endometritis.

 A comparison of the effectiveness of the treatment of endometritis depending on the type of proteinase is presented in table 4.

 From table 4 it is seen that the use of immobilized proteinases in the local treatment of endometritis compared with trypsin can increase the effectiveness of treatment, reduce the number of procedures and the amount of the drug, and also avoid adverse allergic, pain reactions.

 The experience of using immunozyme in a clinic on the example of 57 patients showed that a positive effect of treatment is observed with any clinical course of endometritis (catarrhal, purulent, purulent-catarrhal). In any case, with this application of the selected doses, there were no complications, intolerance to the drug and treatment inefficiency. Normalization of the nature of the discharge, the disappearance of soreness occurs within 4-5 days.

 These results could not be foreseen based on the general level of knowledge, since

1. in the literature there is no information about the properties of immobilized proteolytic enzymes introduced into the uterine cavity;
2. there is no information about a single and course dose of the immunosym for intrauterine administration.

 Thus, due to the fact that in the known patent and scientific and technical sources there is no information on the use of immozyme for the treatment of inflammatory diseases of the uterus, it can be concluded that the claimed method meets the criteria of the invention inventive step.

 Example 1. Patient P. 29 years old (N case history 1581), was admitted to the department 02/13/89, about acute endometritis against the background of an intrauterine contraceptive. At the same time, an increase in the size of the uterus, a lack of clarity of its contours, sharp pain on palpation and movement of the cervix, and abundant mucopurulent discharge were noted. The diagnosis is confirmed by the data of additional examination methods. From the first day, the patient received complex antibacterial, desensitizing, anti-inflammatory therapy, exposure to physical factors. On the 3rd day of treatment, when the clarity of the uterine contours appears and after removal of the IUD, treatment with intrauterine instillations of the immunozyme with an activity of 75 PE / ml is started.

 The drug at a dose of 375 PE (5 ml of the drug) under aseptic conditions after treatment of the cervix with an antiseptic was injected into the uterine cavity with a Record syringe with an adapted uterine tip from a Brown syringe. The patient maintained a horizontal position for 3-4 hours.

 The procedure was performed once a day daily. It took 3 injections to eliminate the pain of the uterus, normalize the discharge, and in general, the course of inpatient treatment took 8 days.

 Example 2. Patient C., 41 years old (case history No. 575), was admitted to the pathology department on January 16, 1990 due to exacerbation of chronic metroendometritis and left-sided adnexitis of nonspecific etiology with a moderate general and focal reaction. Suffers from chronic inflammation of the internal genital organs 15 years, the last exacerbation 5 years ago. This associates with hypothermia. Within 2 years, uterine fibroids are determined. Comprehensive anti-inflammatory treatment was started from the moment of admission during examination by combined provocation. Local treatment with intrauterine instillations of the immunozyme began on the 4th day of treatment in parallel with antibiotic therapy. A drug with an activity of 50 PE / ml was administered 1 time daily for 5 days. The effectiveness of treatment, including clinical symptoms, was assessed by the results of hysteroscopy, which recorded the disappearance of edema of the endometrium, purulent-fibrinous plaque, normalization of the vascular pattern. Inpatient treatment was carried out for 10 days.

 Example 3. Patient A., 31 years old (medical history 1362), was admitted to the department 02/08/89, with a diagnosis of Acute endometritis, bilateral salpingitis, probably of a specific etiology. Sick two days ago after menstruation. Upon receipt, symptoms of a pronounced general and focal reaction, acute phase changes in blood tests. From the moment of admission, infusion antibacterial, detoxification, desensitizing, restorative therapy was carried out, physiotherapy was started from the 2nd day, and resolving therapy was connected from the 6th day. After the removal of the phenomena of intoxication, the reduction of focal manifestations of the inflammatory process of the genitals, local treatment with intrauterine instillations of the immunosymic activity of 60 PE / ml was started. The procedure was performed twice in 2 days. After the first administration of the immunozyme in a dose of 300 PE (5 ml), a significant decrease in uterine pain was noted, which disappeared after repeated instillation.

 The effectiveness of treatment was additionally evaluated by cytomorphological indicators of aspirates from the uterine cavity, where the prevalence of lymphocytes over neutrophils, the appearance of macrophages and histiocytes, characteristic for recovery, are fixed. The course of inpatient treatment in this case lasted for 10 days.

 Example 4. Patient K., 28 years old (medical history N 4058), was admitted to the department on May 28, 1990 with a diagnosis of Acute postabortion endometritis. The presence of residues of the fetal egg in the uterine cavity is excluded by ultrasound. Complex anti-inflammatory treatment with local sanitation of the uterine cavity with an immunozyme activity of 20 PE / ml (dose of 100 PE / 5 ml) was started on the 1st day. The procedures were carried out daily for 8 days with continuing long-term pain in the uterus and the absence of normalization of the nature of the discharge, which forced to abandon further use of this method and end the treatment in the traditional way. The course of treatment in this case in a hospital lasted 15 days.

 Example 5. Patient K., 34 years old (medical history 2872), was admitted to the department on 1.06.1990 due to exacerbation of chronic endometritis with a moderate general and focal reaction. Suffers from the inflammatory process for 6 years, the onset of the disease is associated with the IUD, this exacerbation is provoked by hysterography. Comprehensive anti-inflammatory treatment included topical treatment with immunozyme, initiated after examination with provocation. For intrauterine administration, a preparation with an activity of 110 PE / ml in an amount of 5 ml was used, administered only once, because 4 hours after the procedure, the patient had a moderate pain reaction, and after 10 hours the appearance of moderate bloody discharge from the genital tract. This forced to interrupt local treatment for 4 days, supplementing the complex treatment with a hemostatic component. Repeating the procedure after 4 days was accompanied by similar manifestations. The hospital treatment course ended traditionally, only 17 days.

Using the proposed method of treatment in comparison with the prototype will allow:
1. reduce the treatment time for inflammatory diseases of the uterus by an average of 3-5 days;
2. apply the drug in conjunction with antibiotics and antiseptics of a wide spectrum of action, because in a gentle mode, the immunozyme does not reduce activity, but retains its specific activity.

Claims (1)

 A method for the treatment of endometritis, including the intrauterine administration of a drug, characterized in that they use immozyme in a single dose of 200 to 1125 PE in a volume of 4 to 5 ml, performing 3 to 4 injections.

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