RU2238740C2 - Method for treating nephropathy in neonatals - Google Patents

Abstract

FIELD: medicine, neonatal nephrology.

SUBSTANCE: the present innovation deals with general background therapy and , moreover, it is necessary to introduce tysol with heparin and tysol with proserine for a patient once daily by applications onto patient's skin in lumbar area in the region of renal projection and in suprapubic area in the region of bladder's projection, correspondingly. Then comes the second course of therapy when patient is prescribed to apply tysol with euphylline by application once daily onto the skin of jugular and lumbar vertebral departments. Each procedure should last for 5-10 min, therapy course corresponds to 10-15 d. The method enables to stimulate renal growth, restore rheology and urodynamics along with decreased quantity of pharmacological preparations introduced into neonatals.

EFFECT: higher efficiency of therapy.

1 ex

Description

The invention relates to medicine, namely to methods of treatment, including the introduction of drugs into the body by diffusion through the skin, and can be used in nephrology for the treatment of nephropathy in children in the neonatal period.

There is a method of treating nephropathy in children: treatment of patients with an infection of the urinary system, including patients with pyelonephritis, which is based on antibiotic therapy, which includes the introduction of antibiotics and other pharmacological drugs, as well as the use of herbal medicine. Moreover, specific treatment options depend on the clinical parameters of the patient, the nature of the microbial flora, immunological parameters, age of the patient, and concomitant diseases. In addition, in all cases, membrane stabilizers and antioxidants are used for treatment (Nephrology. / Guide. Edited by I.E. Tareeva, Volume 1, M .: Medicine, 1995, p. 433).

Closest to the proposed is a method of treating nephropathy in children in the neonatal period (a method of treating patients with an infection of the urinary system, including patients with pyelonephritis), in accordance with which the patient is given a course of antibacterial therapy. In this case, the patient is injected with drugs with a wide spectrum of action that can suppress both gram-negative and gram-positive flora (A.V. Papayan, I.S. Styazhkin Neonatal Nephrology. / Guide, St. Petersburg: Peter, 2002, p. 361).

A disadvantage of the known methods lies in their one-sided focus of treatment: elimination of the microbial-inflammatory process in the kidneys and urinary tract, elimination of symptoms of intoxication, i.e. to achieve normalization of urodynamics, only the relief of the inflammatory process is used. However, the small possibilities of drug therapy due to limitations in use for the newborn both in doses and in indications for use reduce the effectiveness of known methods of treatment. In addition, it is known that each age period has a specific functional state of the kidneys. In the neonatal period, children are characterized by the presence of small immature kidneys, which in children with nephropathy, unlike healthy children, do not allow satisfying the needs of the body aimed at maintaining homeostasis. Antibacterial therapy entails the need to introduce additional drugs into the child's body that mitigate the negative effect of antibiotics on him. Usually, in addition to the prevention of dysbiosis, lactobacterin, bificol and their analogues are prescribed. Vitamin therapy is widely used. For the prevention of osteoporosis, vitamin D is prescribed simultaneously with calcium preparations. The one-sided orientation of the known methods of treating nephropathy (stopping the inflammatory process by eliminating the source of infection) not only does not provide for the possibility of enhancing kidney function, but because of the need to administer a large number of pharmacological drugs used in the child’s body, the kidneys are even more loaded. As a result, the effectiveness of treatment is reduced.

Thus, the methods for the treatment of nephropathy in children in the neonatal period, the analogue and the prototype of the proposed method, revealed as a result of a patent search, do not provide a technical result in the implementation, which consists in increasing the effectiveness of treatment due to the possibility of stimulating kidney growth, restoring rheology and urodynamics and at the same time reducing the amount of pharmacological drugs introduced into the child's body.

The present invention solves the problem of creating a method for the treatment of nephropathy in children in the neonatal period, the implementation of which ensures the achievement of a technical result consisting in increasing the effectiveness of treatment due to the possibility of stimulating kidney growth, restoring rheology and urodynamics and at the same time reducing the amount of pharmacological drugs introduced into the child's body.

The essence of the invention lies in the fact that in the method of treating nephropathy in children in the neonatal period, including general background therapy, in addition, the patient is administered once daily with tizol with heparin and tizol with proserin, while the applications are performed on the skin of the lumbar region the patient in the area of the projection of the kidneys and in the suprapubic region in the area of the projection of the bladder, respectively, then a second course of treatment is carried out, in which the patient is injected once a day also through applications of tizol with aminophylline, at the same time, applications are performed on the skin of the cervical and lumbar spine, each procedure is carried out for 5-10 minutes, treatment courses are 10-15 days.

The technical result is achieved as follows. In the proposed method, the possibility of administering drugs by performing applications on the patient’s skin is due to the fact that tizol is used to transport drugs through the skin. Tizol is an aquacomplex of titanium glycerol solvate. It has high permeability through the skin, normalizes the amount of fluid in the tissues, enhances their oxygenation, nontoxic, and mixes easily with medication additives. The shape of the insulation is a white gel. It is applied externally (Pharmacy No. 2, 1994, p. 9-10).

The shape of the insulator is a gel, as well as its ability to mix easily with medical additives, provide the ability to use an insulator for the preparation of compositions for applications. Applying the composition in the form of applications allows you to limit the area of influence of the composition used in the method, which reduces the possibility of negative effects of treatment and thereby increases the effectiveness of treatment. The introduction of drugs into the patient’s body through applications performed on the patient’s skin provides a soft effect of the drugs administered, since in this case they act on the body in a reflexive, humoral way and, moreover, have a local effect; provide a more gradual entry into the body, a longer effect on the body due to the formation of a depot of the injected medicinal substances in the skin, painlessness of the administration of drugs, non-invasiveness, and the absence of tissue deformation that occurs with other methods of pharmacotherapy due to the introduction of a solvent that increases the amount of medication administered simultaneously. when prescribed intramuscularly or subcutaneously. All this contributes to the most complete penetration through the skin of the components of the composition and increases both the biological activity of the administered compounds and the effectiveness of their therapeutic effect. Moreover, due to the non-toxicity of the insulation, the possibility of pathological changes in the skin that can occur with prolonged use of artificial accelerators of absorption is excluded.

As already mentioned above, each age period is characterized by a certain functional state of the kidneys. In the neonatal period, the presence of small immature kidneys is characteristic of children. Since renal hypoplasia is a rather rare condition, we mean the more common term “small kidney”, the nature of which is extremely diverse (Nephrology / Manual. Edited by I.E. Tareeva, Volume 1, M .: Medicine, 1995, p. 409, p. 421).

It is believed that a reliable diagnosis related to nephropathy can be made only after three months of life. To assess kidney function in newborns, standards related to older children and adults cannot be used. Therefore, treatment in the neonatal period was to maintain life, creating conditions for nursing a child.

However, it is known that acute renal failure in young children in approximately 70% of cases occurs in the first week of life. Moreover, in about 80% of children, the disease in the first month of life is caused by a congenital structural abnormality of the kidneys and urinary tract, as well as hypoxia. The causes of acute renal failure may include renal vein thrombosis, renal artery thrombosis (Pediatrics. Translated from English under the editorship of Prof. I.M. Vorontsov, M .: Medicine, 1988, p. 412; p. 413, table 13 -thirteen). In addition, children with birth injuries of the central nervous system have their own characteristics in the formation of bladder function. A hyperreflex bladder is more often formed during hypoxic-traumatic injuries of the brain, and a hyporeflex bladder is formed during injuries of the cervical and lumbar spine (A.V. Papayan, I.S. Styazhkin. Neonatal Nephrology. / Guide, St. Petersburg: Peter, 2002, p. 216). The presence of these factors gave rise to the neonatal period, in addition to targeted targeted therapy aimed at the treatment of nephropathy.

Heparin belongs to direct anticoagulants - fast acting, effective in vitro and in vivo. The latter allows you to enter it percutaneously, namely through applications, using the conductive properties of the insulation. Heparin is used to prevent thrombosis and in violation of microcirculation. Heparin, when ingested, is concentrated in the liver and spleen. Reduces blood viscosity, reduces vascular permeability. It is a biologically active substance of a regulatory nature. It provides direct stimulation of autonomic (perivascular plexuses, mast cells) or cerebrospinal (cutaneous endings of cerebrospinal nerves) peripheral reflex elements (Russian Drug Register 99, p.565). As a result, the introduction of heparin prevents thrombosis, normalizes blood flow in the kidneys, improves microcirculation and indirectly eliminates renal hypoperfusion. This, in turn, normalizes the function and growth of the kidneys, and therefore, urodynamics.

In addition, since heparin is introduced into the patient’s body by performing applications on the patient’s skin, the effect of the drug is primarily perceived by the skin receptors (V.T. Oliferenko. Hydrotherapy., M .: Medicine, 1986, p. 111). Skin receptors transform the external effect into a nerve impulse that reaches the central nervous system and serves as the basis for the formation of a holistic reaction of the body (B.C. Ulashchik. Essays on general physiotherapy. Minsk: "Navuka i tehnisa", 1994, p. 81). Based on this, it follows that for maximum saturation with the drug introduced through the skin, skin receptors should not perceive negative interaction with it, since otherwise the signal generated by the skin receptors in the central nervous system will lead to the formation of a protective-adaptive reaction as the skin itself : spasm of blood vessels of the skin and a sharp decrease in permeability, as well as the formation of a protective and adaptive reaction associated with organs projected onto these skin areas. It is known that heparin is an acid mucopolysaccharide produced in the human body by basic leukocytes, which is found in the largest quantities in the liver and lungs; special receptors for endogenous heparin analogues were found on the surface of endothelial cells. As a result, heparin is an integral part of the body's vital product, and therefore it is adequate to the body and, when it enters the body, does not negatively affect it in general. Heparin has an antiallergic (prohormonal) effect, which is important because the body of a child, especially a newborn, is very sensitive to interventions from outside. Thus, heparin is adequate to the human body and does not cause the formation of negative adaptive reactions by skin receptors when it is introduced through the skin, which contributes to its more complete penetration to the diseased organ and increases the effectiveness of treatment.

It is known from homeopathy that small doses of drugs affecting the body are weak irritants and the signals caused by them pass unhindered into the nerve centers without inhibiting them and not suppressing the body's defenses, i.e. without causing negative adaptive reactions to the impact (V.A. Linde Homeopathy in obstetrics and gynecology. St. Petersburg: Publishing House "G and F", 1977, p.28). The high penetrating ability of thysol through the skin, nontoxicity of thysol and the adequacy of heparin to the human body allow the use of minimal doses of the drug for treatment, which is especially important for the neonatal period, as it facilitates the work of the kidneys and increases the effectiveness of treatment. As a result, blood circulation in a small immature kidney increases, oxygen saturation increases, which improves the working conditions of the kidneys and stimulates their growth, and therefore increases the effectiveness of treatment.

Proserine causes an increase in contractility of smooth muscles. They are used for atony of the bladder (Russian Medicines Register 99, p.851).

Due to the fact that as a carrier through the skin using tizol, which has high transcutaneous permeability, the possibility of using a therapeutic drug in small doses is achieved. The possibility of introducing prozerin into the child’s body in small doses ensures the maximum effect of the drug on the bladder, since small doses of the drug affect organs and tissues, regulating cell functions. (V.A. Linde Homeopathy in obstetrics and gynecology. St. Petersburg: Publishing House "G and F", 1977, p. 28). This ensures the most complete flow of proserin to the diseased organ, and therefore, the maximum effect of the drug on the bladder and increase the effectiveness of treatment.

Due to the fact that applications with heparin and proserin are performed on the skin of the patient’s lumbar region (in the area of the projection of the kidneys) and in the area of the projection of the bladder (in the suprapubic region), the direct effect of the drug through the skin on the diseased organ is ensured, which increases the effectiveness of treatment.

The combined use of prozerin with heparin increases the effectiveness of treatment, since improved kidney function stimulates an improvement in bladder function at the same time. As a result, urodynamics improves. This allows you to reduce the duration of the course of antibiotic therapy, and therefore, reduce the number of injected antibiotics and other pharmacological drugs, which also facilitates the work of the kidneys and contributes to an even greater improvement in urodynamics. As a result, the combined use of heparin and prozerin can increase the effectiveness of treatment while reducing the number of pharmacological drugs administered.

The use in the claimed method of treating nephropathy in children in the neonatal period of formulations containing tizol also provides an increase in the effectiveness of treatment. This is achieved due to the fact that in the proposed method for the treatment of nephropathy, tizol is used not only as the basis of the gel for applications and transport of the active ingredient, but, in addition, it is used as an independent drug that helps to improve kidney function, stimulate their growth and improve urodynamics, what was not previously known.

The following are the results of studies confirming the presence in the insulator properties that contribute to the improvement of kidney function, stimulation of their growth and improvement of urodynamics, against the background of local therapy with tizol. Studies were performed on a group of patients from 18 people. Each patient underwent general background therapy individually.

Research results. The terms of stopping dysuria (pastiness, edema, oliguria) by the fifth day - 7 people, by the tenth day - 11 people; preservation of urinary syndrome: normalized by the tenth day in 18 people; restoration of the parameters of functional tests: the Zemnitsky test returned to normal on the 10th day in 12 people; change in indicators of instrumental examination: a decrease in the size of the pelvis in 12 people, an improvement in parenchyma in 10 people.

From the results of the studies, it can be seen that tizol positively affects the clinical picture of nephropathy, exerting a therapeutic effect on the kidneys and bladder, which consists in improving the functioning of the kidneys, stimulating their growth and improving urodynamics.

In addition, the inventors have proved that in the proposed method tizol is not only an active conductor through the skin, but, forming the corresponding complexes with heparin and proserin, it provides targeted transport of these drugs directly to the diseased organ. This is confirmed by a spectral study of urine, which showed that after one day of treatment, the basal level of titanium was 0.01 μg / ml. After a ten-day use of drugs with tizol, the titanium level increased to 0.24-0.31 μg / ml.

Eufillin is used for chronic cerebrovascular insufficiency, impaired renal blood flow. One of the pharmacological actions of aminophylline is diuretic (Russian Medicines Register 99, p.885). It is known that the functional state of the kidneys in a child is under complex neurohumoral control. Due to the choice of zones of exposure to the patient’s skin through the application: on the skin of the cervical and lumbar spine, aminophylline affects the function of the kidneys through the central nervous system, penetrating into it through the circulatory system.

The body's response to the impact (in our case, an external factor) depends on the place of its application. This is due to the specifics of the organization of the nervous system, through which both effects and responses to them are carried out. The application of thysol with euphyllin simultaneously on the skin of the cervical and lumbar spine has a medicinal effect on the entire spinal column as a whole, which increases the effectiveness of treatment, since damage to the cervical and lumbar spine and spinal cord are the most common during birth injuries associated with the central nervous system , and causing hyporeflectivity of the bladder (A.V. Papayan, I.S. Styazhkin. Neonatal Nephrology / Guide. St. Petersburg: Peter, 2002, p.216). The state of the autonomic nervous system is determined by the regulatory effect on the capillary network, lymph vessels, etc. Eufillin regulates the tone of the autonomic nervous system, affecting the state of blood vessels, improves renal blood flow (Russian Drug Register 99, p. 885). From homeopathy, it is known that large doses of a drug affect the central nervous system, and small doses affect organs and tissues, regulating cell functions (V.A. Linde. Homeopathy in obstetrics and gynecology. St. Petersburg: Publishing House "G and F", 1977, p. 28). The aminophylline used in the method provides an effect on the central nervous system. The result is improved hemoliquorodynamics, normalization of the autonomic nervous system, stimulation of metabolism in the brain structures.

The use of thysol to transport aminophylline through the skin due to the nontoxicity of thysol does not cause negative adaptive reactions of the body, in contrast to the conventional administration of aminophylline by electrophoresis, which increases the effectiveness of treatment.

The course of thysol with heparin and thysol with proserin has an operative therapeutic effect directly on the affected organs, and the course of thysol with euphilin fixes this medicinal effect through the regulatory effect of the central nervous system on the state of the whole organism.

As a result, in the claimed method for the treatment of nephropathy in children of the neonatal period, an increase in the effectiveness of the treatment is provided due to the synergistic effect created by the ingredients of the compositions used in the method during the first course of treatment, namely: thisol with heparin and thysol with proserin, as well as due to the synergistic the effect obtained from the courses of treatment created by the above compositions and the composition of thysol with euphyllin. At the same time, the possibility of obtaining a synergistic effect from the combined use of thysol with heparin and thysol with proserin is provided by introducing the ingredients of each composition by performing applications on the patient’s skin, which allows two medicinal preparations to be administered simultaneously: tizol with heparin and tizol with proserin.

The number of applications per day: once a day for 5-10 minutes and the duration of treatment courses of 10-15 days are determined empirically and are optimal for obtaining a sustainable effect from treatment, which also provides an increase in the effectiveness of treatment. The duration of the procedure depends on the condition of the child, since the duration of the procedure determines the amount of drug administered. The possibility of varying the duration of the procedure and the duration of the treatment allows you to take into account the individual needs of the patient's body, which also increases the effectiveness of the treatment.

Performing general background therapy allows you to take into account the individual characteristics of nephropathy in each sick child, which ensures increased treatment efficiency.

From the foregoing, it follows that at the first stage of treatment, thanks to the introduction of thysol with heparin and thysol with proserin by means of applications, moreover, applications are performed on the patient’s skin on the lumbar region in the area of the projection of the kidneys and in the area of the projection of the bladder (in the suprapubic area), thereby the most direct effect on the diseased organ, the proposed method for the treatment of nephropathy in children of the neonatal period provides improved microcirculation and blood flow in the kidneys, stimulates kidney growth and stabilizes the ugly Namik. Renal artery Doppler data obtained from studies in a group of 42 patients showed restoration of blood flow after 10-14 days of treatment. The second course of treatment by performing thysol with euphyllin simultaneously on the skin of the cervical and lumbar spine consolidates the effect of the first course of treatment, having a positive effect on the function of the kidneys and bladder through the regulatory effect of the central nervous system, improving hemoliquorodynamics, normalizing the activity of the autonomic nervous system, stimulating metabolism in the brain structures, which as a result enhances stimulation of kidney growth and stabilization of urodynamics. As a result, the effectiveness of treatment increases. Due to the fact that the claimed method accelerates the normalization of renal function and urodynamics, the treatment time is shortened and, as a result, the number of pharmacological drugs introduced into the body of a newborn baby, including antibiotics, is reduced.

In addition, the claimed method expands the possibilities of drug therapy in the treatment of nephropathy in newborns, expanding the arsenal of drugs.

Thus, the claimed method for the treatment of nephropathy in children in the neonatal period during the implementation ensures the achievement of a technical result consisting in increasing the effectiveness of treatment due to the possibility of stimulating the growth of the kidneys and at the same time reducing the number of pharmacological drugs introduced into the child's body.

A method for the treatment of nephropathy in children in the neonatal period was performed as follows. The child received general background therapy depending on the state of health. In addition, the patient was administered once daily with tizol with heparin and tizol with proserin through applications. Applications were performed on the skin of the lumbar region of the patient in the area of the projection of the kidneys and in the suprapubic area in the area of the projection of the bladder, respectively. Then, a second course of treatment was carried out, in which the patient was injected once a day also with tizol and euphyllinum applications. Applications were performed on the skin of the cervical and lumbar spine. The procedure was carried out for 5-10 minutes, treatment courses were 10-15 days.

The content of background therapy was determined by the state of the patient's body.

Medicines were taken in accordance with generally accepted methods of therapy, taking into account the age and weight of the child. To perform the method, mixtures of ingredients were prepared: tizol - heparin, tizol - proserin, tizol - aminophylline. Mixtures were prepared in advance by a pharmacist. In the above example, the method of tizol was mixed with 100 IU of heparin per kilogram of weight, with 0.02% proserin, 2% aminophylline. The required amount of insulation was determined depending on the area of application. In the above example, the insulation was taken for one application of 1.5 g. The finished preparation was applied, for example, with a spatula, with a thin layer on the skin area of the child in the form of an application.

The treatment courses were: tizol - heparin 15 days, tizol - proserin 15 days, the duration of each procedure is 7 minutes; tizol - aminophylline - 10 days, the duration of each procedure is 10 minutes.

When performing applications from thysol with heparin and thysol with proserin, the applications were positioned respectively similar to the location of the electrodes on the patient’s back when performing electrophoresis on the renal region and on the abdominal wall above the pubic joint when performing electrophoresis on the bladder (Physiotherapy Guide edited by prof. B .G. Yasnogorsky. M: Medicine, 1992, p. 47).

When performing applications from insulation with eufillin, applications were arranged similarly to the electrodes when performing electrophoresis when exposed to the collar region (Handbook of Physiotherapy, edited by Prof. V.G. Yasnogorsky, M .: Medicine, 1992, p. 37).

Example 1. Patient Vova E., Department of pathology of the newborn. Birth weight 2900 g, length 50 cm. Apgar score 5/7 points. Condition at birth of moderate severity. At the age of three days with a diagnosis of chronic intrauterine hypoxia, cerebrovascular accident, aspiration syndrome, the child was transferred to the neonatal pathology department.

Diagnosis: perinatal CNS trauma of mixed origin, ichthyosis, metabolic nephropathy, early diagnosis in the recovery period - hypertensive hydrocephalic syndrome.

The clinic noted: pallor, dry skin, large-plate peeling, pasty eyelids, acrocyanosis, unstable stool, and decreased urination. Both kidneys were palpated. In urinalysis, proteinuria (0.03-0.06%), hematuria (20-30 in p / vision), a large number of salts (urates, oxalates) were detected. In the general analysis of blood, anemia, a neutrophilic shift to the left. In a biochemical blood test revealed hypoproteinemia, an increase in urea (7.6 mmol / l); LDH is 1.6 times higher than normal; β ₂ - MG in the blood serum was normal; β ₂ - MG in urine - at the upper limit of normal. According to ultrasound: the kidneys are usually located, the contours are fuzzy, the sizes are less than the age norm, the paronym on both sides is 8 mm with dense foci, the collective system is expanded.

The child received background therapy, antibacterial, chimes, vitamins, enzymes, lasix, biological products. In addition, the child was treated in accordance with the claimed method. In addition to general background therapy, the patient was once once a day alternately performed on the skin of the lumbar region in the area of the projection of the kidneys and in the area of the projection of the bladder, respectively, applications of tizol with heparin and tizol with proserin. Then, a second course of treatment was carried out, in which the patient was injected once a day also with tizol and euphyllinum applications. Applications were performed on the skin of the cervical and lumbar spine.

DPPA recovered on the seventh day. Bladder function returned to normal on the fifth day of treatment. Partial renal function normalized by the twelfth day. The manifestations of hypertensive hydrocephalic syndrome disappeared, normalization of cerebrospinal fluid dynamics was noted.

At the age of twenty-nine days, the child was discharged home under the supervision of a nephrologist.

Thus, the claimed method accelerates the normalization of renal function and urodynamics, reduces treatment time and, as a result, reduces the number of pharmacological drugs introduced into the body of a newborn baby, including antibiotics.

Claims (1)

A method for the treatment of nephropathy in children in the neonatal period, including general background therapy, characterized in that the patient is administered once daily with tizol heparin and tizol with proserin, the applications being performed on the skin of the lumbar region of the patient in the area of the projection of the kidneys and suprapubic region in the area of the projection of the bladder, respectively, then a second course of treatment is carried out, in which the patient is also injected once a day also with tizol applications with euphyllin, while applications are performed on in the cervical and lumbar spine, each procedure is carried out for 5-10 minutes, course of treatment is 10-15 days.