Method for preventing and(or) treating anemia in children (variants)

FIELD: medicine, pediatrics, hematology.

SUBSTANCE: the present innovation could be applied in treating surgical and oncological diseases in children during treating and preventing anemia of different etiology. One should introduce ceruloplasmin at daily single dosage ranged 50-200 mg depending upon child's age against 100-200 ml 0.9%-sodiumchloride solution intravenously by drops at the rate of 40-50 drops/min. Moreover, for preventing and/or treating posthemorrhagic anemia in case of surgical operations one should introduce ceruloplasmin during 2 d before surgical operation, intraoperationally, and for 2-10 d after operation. For preventing and/or treating anemia in case of purulent-septic diseases ceruloplasmin should be introduced during chemotherapeutic days during the whole period of the course conducted, for preventing and treating radiation anemia at the background of radiation therapy ceruloplasmin should be injected once weekly during the whole period of radiotherapy course, for preventing and treating toxic and radiation anemia at the background of chemoradiation therapy ceruloplasmin should be introduced once weekly on the day of chemotherapy during the whole course of chemoradiation treatment. The innovation enables to avoid inflows of erythrocytic mass and donor's blood along with shortened number of procedures on introduction of ceruloplasmin and 4-times decrease in the risk for the development of severe anemia in children due to matching peculiar mode for ceruloplasmin introduction.

EFFECT: higher efficiency of therapy and prophylaxis.

4 cl, 5 ex

 

The present invention relates to medicine, namely to Pediatrics and Hematology, and can be used in the practice of the treatment of surgical and oncological diseases in children for the prevention and treatment of anemia of various etiologies (posthemorrhagic, toxic, radiation and others).

Anemia is the most common hematological diseases in children. Despite the fact that at the present time, we have accumulated rich clinical experience in the diagnosis and treatment of iron deficiency, hereditary haemolytic malatrasi, there is no clearly developed corrective actions in these States. The practitioners is difficult to corpii patients with manifestations of acute and chronic posthemorrhagic anemia at the height of the tumor intoxication, on the background of immunodeficiency induced by chemoradiation therapy. Often posthemorrhagic diathesis remains in children, even several weeks after surgery, resulting in increased length of stay in hospital and require additional monitoring of physicians outpatient network. For patients incoherencies hospitals require timely correction of anemia due to the need for post-operative chemotherapy and radiation treatment within a clearly defined timeframe, failing which the face an increased risk of metastasis and recurrence of ecoprocess.

Currently, the most common method of correction of anemia, including children, is the transfusion of red blood cell mass [1]. The transfusion of erythrocyte mass and the washed erythrocytes doesn't always help in the fight against developed anemia, there is a high risk of the development of numerous hepatitis, acquisition of HIV, as well as additional allergies weakened the child's body. The main complications of blood transfusion are febrile and hemolytic reactions, development of alloimmunization and refractoriness to transfusion, infection infectious diseases, the development of graft-versus-host. Transfusion of donor blood preparations, there is a high risk of infection in children with cytomegalovirus, HIV, virus, Esptein Bar, hepatitis, malaria, syphilis, blood transfusion from donors with mild forms of hemoglobinopathy can cause death in newborns in the state of hypoxia, lead to hyperkaliemia, hypocalcemia. According to different authors, adding to the diet of iron supplements, folic acid and vitamin E (tocopherol) does not prevent the development of anemia [2].

For the prototype of the present invention, the selected method for the prevention and treatment of anemia in children, including the introduction of drugs, namely recombinant Erythro aatina [3]. The method consists in the fact that this drug was administered at 150 IU/kg subcutaneously 3 times per week for 12 weeks, however, the high cost of recombinant erythropoietin and the technical complexity of its production does not allow you to present extensively to implement it in practical medicine, which led to the search for new ways to prevent and treat anemia in children.

The task of the invention is given: the development of a method of treatment of anemia in children with the use of drugs with low cost and which is characterized by the technical ease of production with high efficiency correction and prevention of anemia.

The task for option 1 is achieved by the fact that under paragraph 1 of the claims as drugs used ceruloplasmin, which is administered in a daily dose of from 50 to 200 mg depending on the age of the child, 100-200 ml of 0.9% solution of sodium chloride intravenous infusion at a rate of 40-50 drops per minute for 2 days preoperatively, intraoperatively and within 2-10 days after the operation.

The task for option 2 is achieved by the fact that paragraph 2 of the claims as drugs used ceruloplasmin, which is administered in a daily dose of from 50 to 200 mg, depending upon ascending the hundred child, 100-200 ml of 0.9% solution of sodium chloride intravenous infusion at a rate of 40-50 drops per minute for 7-10 days, in parallel with the carrying out of antibacterial therapy.

The task for option 3 is achieved by the fact that paragraph 3 of the claims as drugs used ceruloplasmin, which is administered in a daily dose of from 50 to 200 mg depending on the age of the child, 100-200 ml of 0.9% solution of sodium chloride intravenous infusion at a rate of 40-50 drops per minute. For the prevention and treatment of toxic anemia due to chemotherapy ceruloplasmin give the entire course in the days of hemiauchenia, for the prevention and treatment of radiation anemia on the background of radiation therapy ceruloplasmin enter 1 time per week throughout the course of radiotherapy, and for the prevention and treatment of toxic and radiation anemia on the background of chemoradiation therapy ceruloplasmin enter 1 time per week on the day of chemotherapy during radiation therapy. At the same daily dose of ceruloplasmin depending on the age of the child is chosen as follows: children under 1 year - 50 mg, from 1 year to 12 years - 100 mg, 13-18 years - 200 mg

Ceruloplasmin is a copper-containing oxidase, refers to alpha-2-globulin fraction of human blood plasma. Copper is a 0.27-0.32 per cent of the total weight of the protein. the first in the pure form of this enzyme was obtained in 1948 Holmberg. It was found that derivatives of tissue methoxide contribute to the development of blood stem cells and protect them from the damaging effects of various external factors. The main functions of ceruloplasmin in the body is to transport copper, mobilization of serum iron for blood formation, antioxidant activity and inhibition of lipid peroxidation, involved in acute phase reactions, regulation of the level of biogenic amines in the body. The results of the advanced clinical research would recommend ceruloplasmin for the treatment of anemia of different etiology in adults. We found that this protein functions as ferroxidase, oxidizing ferrous iron to ferric, which is incorporated into the molecule of transferrin and is transported to the bone marrow, where the synthesis of heme. In 1961 initiated clinical application of ceruloplasmin in adults background mutilating surgeries for tumors in the treatment of traumatic and posthemorrhagic shock, radiation sickness, burns, septic pathology [4].

Earlier in children ceruloplasmin was never applied. In the present invention first shown the principal possibility of application of ceruloplasmin in children. A special study of the authors of this application showed the prob is the possibility of using this drug in the practice of the treatment of children of different ages from 1 year to 18 years with surgical and oncological diseases. Developed conditions (dose, scheme, method of administration), subject to which the application of ceruloplasmin in children causes no side effects at high clinical results of the correction of anemia. In particular, the authors of this application for the first time established that the child practices the most effective are: 1) single daily dose of 50 to 200 mg (depending on age of child: under 1 year - 50 mg; from 1 year to 12 years - 100 mg, 13-18 years - 200 mg); 2) intravenous administration at a speed of 40-50 drops per minute (earlier in practice, treatment of ceruloplasmin in adults was used intravenous speeds 30-36 drops per minute); 3) the use of isotonic sodium chloride (in adult practice is used as an isotonic solution of sodium chloride and 5% glucose solution).

Developed and substantiated schemes of ceruloplasmin in children in the prevention and treatment of various anemias (3 variants).

It has been shown that for the prevention and / or treatment of posthemorrhagic anemia ceruloplasmin children must be entered within 2 days preoperatively, intraoperatively and then within 2-10 days after surgery. This is justified as follows: we studied the different schemes under the control of the blood test results and obtained the following results: introduction 7-3 days before the operation was given t is coy same effect as the introduction for 2 days before surgery; the introduction of only 1 day prior to surgery is not enough (the effect is worse than 2 days prior to surgery);

introduction after surgery for more than 10 days did not give further rise effect, i.e. after the operation optimally 2-10 days of injections). Intraoperative introduction ceruloplasmin necessarily: if at this point the drug is not recommended, it has lower effect correction, in addition, during operative intervention if blood loss is significant simultaneous loss of body iron and copper and the output of ceruloplasmin from the tissues that quickly are also corrected with the introduction of exogenous drug.

In the prevention and treatment of anemia in purulent-septic diseases in children ceruloplasmin must be entered within 7-10 days, in parallel with the carrying out of antibacterial therapy. The expediency of application of this scheme is proved by the authors of this application as follows: it is concurrent with the antibiotic therapy, the rate which is on average 7-10 days, the introduction of ceruloplasmin provides optimal blood and antioxidant effect. It is at the height of intoxication and fever is massive depression of hematopoiesis, in addition, bacterial agents often wideset hemolytic enzymes times is ucheniu erythrocytes, therefore, it is necessary the introduction of ceruloplasmin immediately after opening purulent, along with antibiotic therapy.

For the prevention and treatment of toxic anemia due to chemotherapy in children with cancer ceruloplasmin, you must enter the entire course of chemotherapy in the days of chemotherapy (e.g., daily for 5 days, if the chemicals are introduced on a five-day continuous scheme; or when the treatment regimen No. 2 in the days of hemiauchenia - 1st, 8th, 15th). It should be noted that the adults for the prevention and treatment of toxic anemia due to chemotherapy ceruloplasmin always enter 3 times per week. As showed researches of the authors of this application, children this scheme is not suitable, because cytopenia and anemia develops in them at 7-10 days after chemotherapy with 5-day scheme or before the second introduction of the 15-day scheme. They are more pronounced intoxication symptoms (nausea, vomiting, weakness), which does not allow to take into iron supplements, folic acid, tocopherol. Introduction leukocyte colony-stimulating factor has as side effects of the property to inhibit erythroid Rostock bone marrow, so you need it to intravenous ceruloplasmin in parallel and at the end of chemotherapy.

For the prevention and treatment of radiac the availability of anemia on the background of radiation therapy in children ceruloplasmin, you must enter during the entire course of radiation therapy 1 time a week. Adults in this case shows the introduction of ceruloplasmin 3 times a week. The authors of this application for the first time the necessity of the use of children scheme with the introduction of 1 time per week. This is substantiated clinical and laboratory data, with the introduction of ceruloplasmin intravenous drip on the background of radiation therapy 1 time a week for 7 weeks does not develop anemia, which does not interrupt the radiation treatment, with more frequent drug effect is similar. If you assign ceruloplasmin less than 1 times a week, anemia, join signs of radiation poisoning (nausea, vomiting, radiation gastritis, esophagitis), it is necessary to interrupt the treatment.

The proposed method is as follows:

1. For the prevention and / or treatment of posthemorrhagic anemia during surgery in children take ampoule liofilizirovannogo ceruloplasmin, containing 100 mg, throw the preparation of 5 ml of 0.9% sodium chloride solution until complete dissolution of the powder and reconstitution soft blue color. This solution is dissolved in 200 ml of 0.9% sodium chloride solution and injected intravenously at a speed of 40-50 drops per minute. Children up to 1 year administered 100 ml of the prepared solution (50 mg of ceruloplasmin), from 1 year to 12 years - 200 ml (100 mg of ceruloplasmin). Children from 13 to 18 years introduced 200 ml of solution, with the holding of 200 mg of ceruloplasmin, i.e. take 2 capsules liofilizirovannogo ceruloplasmin 100 mg, planting drugs as indicated above, and also injected intravenously. The drug is administered within 2 days preoperatively, intraoperatively and within 2-10 days after the operation.

2. For the prevention and / or treatment of anemia in children with purulent surgical diseases take ampoule liofilizirovannogo ceruloplasmin, containing 100 mg, throw the preparation of 5 ml of 0.9% sodium chloride solution until complete dissolution of the powder and reconstitution soft blue color. This solution is dissolved in 200 ml of 0.9% sodium chloride solution and injected intravenously at a speed of 40-50 drops per minute. Children up to 1 year administered 100 ml of the prepared solution (50 mg of ceruloplasmin), from 1 year to 12 years - 200 ml (100 mg of ceruloplasmin). Children from 13 to 18 years introduced 200 ml of a solution containing 200 mg of ceruloplasmin, i.e. take 2 capsules liofilizirovannogo ceruloplasmin 100 mg, planting drugs as indicated above, and also injected intravenously. The drug is administered for 7-10 days daily days of antibiotic therapy.

3. For the prevention and / or treatment of toxic and (or) radiation anemia in children with cancer take ampoule liofilizirovannogo ceruloplasmin, containing 100 mg, throw the preparation of 5 ml of 0.9% sodium chloride solution until the full RA is the creation of powder and reconstitution soft blue color. This solution is dissolved in 200 ml of 0.9% sodium chloride solution and injected intravenously at a speed of 40-50 drops per minute. Children up to 1 year administered 100 ml of the prepared solution (50 mg of ceruloplasmin), from 1 year to 12 years - 200 ml (100 mg of ceruloplasmin). Children from 13 to 18 years introduced 200 ml of a solution containing 200 mg of ceruloplasmin, i.e. take 2 capsules liofilizirovannogo ceruloplasmin 100 mg, planting drugs as indicated above, and also injected intravenously. For the prevention and treatment of toxic anemia due to chemotherapy ceruloplasmin give chemotherapy days throughout the course, for the prevention and treatment of radiation anemia on the background of radiation therapy ceruloplasmin enter 1 time per week throughout the course of radiotherapy. For the prevention and treatment of toxic and radiation anemia on the background of chemoradiation therapy ceruloplasmin enter 1 time per week on the day of chemotherapy throughout the course of radiation treatment.

Examples of specific performance of the method is given in the form of extracts from the histories.

Example # 1 illustrates the variant # 1 and variant # 3 proposed method, because at different stages of treatment in the patient required correction posthemorrhagic (option # 1) and toxicity due to chemotherapy (option number 3) anemia. Extract from the history of Bo is esni No. 15888.

Sick PV, 6 months. The diagnosis of Hepatoblastoma right lobe of the liver T3 H0 M0. Sick since August 2002, when the mother noticed the pale skin of a child, loss of appetite, weakness, bulging in the right hypochondrium. The child was examined by a pediatrician at the place of residence, performed ultrasound of the abdominal cavity where it is suspected neoplasm of the liver, in an emergency, the girl delivered in the Oncology Department of the state institution "the CLINIC". For admission in the General analysis of blood was observed HB 91 g/l er 2,8, CTC 0,97, hematocrit 28%, Tr 308 thousand, Le 15400, stab 2%, segmented 60%, Lymphocytes 32%, Monocytes 6%, ESR 8 mm/h Among biochemical parameters revealed hyperlife-2-globulinemia to 14.2%, total protein 57,2 g/l, albumin of 55.2%, haptoglobin 19,2, ceruloplasmin over 400 mg/l, alpha-fetoprotein more than 1000 IU/ml By ultrasound is determined by education, filling the entire right lobe of the liver, a solid character with abnormal blood flow. Next, in an emergency she was transfused dose of 0.5 washed erythrocytes corresponding group and rhesus factor after carrying out tests on group, RH and individual compatibility, however, the hemoglobin level has not risen above 98 g/l, therefore the patient was assigned to intravenous infusion of ceruloplasmin 50 mg per 100 ml isotonic sodium chloride in t is an increase of 2 days before the surgery (laparoscopy, pinch-induced liver biopsy), intraoperatively, and within 2 days after surgery. Further transfusions were not required because the hemoglobin level remained 115 g/L. er 3,5, CTC 0,98. The content of ceruloplasmin decreased to 323 mg/l, normalized levels of alpha-2-globulin and amounted to 9.5%. The girl received high-dose chemotherapy consisting of 2 blocks: carboplatin 3.5 mg/kg 1-5 days intravenous drip, doxorubicin 1 mg/kg 1, 2 days intravenous drip, cisplatin 1.5 mg/kg 15, 16 days intravenous drip. After the 1st block, which ceruloplasmin were not administered, the patient developed severe anemia (HB 70 g/l, er 3, CTC 0,88), double-shimmered washed erythrocytes 0.5 dose, but the HB level remained above 98 g/l throughout the 2nd cycle of chemotherapy, the child was assigned ceruloplasmin 50 mg intravenous infusion in 100 ml of 0.9% solution of sodium chloride each day of chemotherapy, total of 7 injections. In the control blood after chemotherapy HB level was 116 g/l er 3,7, CTC of 0.91. Indications for blood transfusion after the second cycle of chemotherapy was not.

Example 2 illustrates a variant No. 3 of the present invention for the case of the prevention and treatment of toxic and radiation anemia on the background of chemoradiation therapy. Statement of the case history No. 15904. Patient G.T., 6 years. Diagnosis: Anaplastic what I astrocytoma of the cerebellum TK H0 M0. Sick since June 2002, when there were headaches in the morning, nausea, vomiting, unsteadiness of gait, difficulty speaking, examined by a neurologist on a residence and is aimed at consultation of the neurosurgeon SE "the CLINIC". In General, the analysis of blood HB 120 g/l er 4, CTC 0,9, Tr 252 thousand, Le 8200, segmented 61%, eosinophils 7%, basophils 1%, lymphocytes 26%, monocytes 5%, erythrocyte sedimentation rate of 12 mm/h, among biochemical parameters total protein was 79 g/l, was observed hyperlife-2-globulinemia to 13%, the level of ceruloplasmin 400 mg/l After consultation of the neurosurgeon recommended CT scan of the brain, where a tumor of the posterior cranial fossa. After preoperative preparation 05.09.02 performed surgery - craniotomy, removal of a tumor of the cerebellum (histologically anaplastic astrocytoma). The postoperative period was complicated by the development of anemia in the General analysis of blood from 08.09.02 HB was 75 g/l, er 2,4, CTC 0,93. Applied transfusion of washed red blood cells of the corresponding group and rhesus factor after carrying out tests on group, RH and individual compatibility (all negative) in a volume of 150 ml, but in controlling the blood after transfusion remained anemia, hemoglobin levels did not rise above 103 g/l Eure was 3.3 CTC - 0,92. Next, the girl was transferred from the Department of neurosurgery in the Department of the children's Oncology where she was assigned to chemoradiation treatment: lomustin 70 mg once inside, vincristine 1 mg intravenous bolus 1 time per week for 7 weeks radiation therapy of a lesion in the cumulative total dose of 55 Gy. As Antianemic means she was appointed ceruloplasmin intravenous infusion 100 mg in 200 ml of 0.9% sodium chloride solution, 1 time per week (7 weeks), i.e. during the whole course of chemoradiation therapy. Before treatment the patient was given a complete clinical and laboratory examination, including complete blood count, which noted the following indicators: HB 98 g/l er 3,2, CTC 0,92, Le 18200, erythrocyte sedimentation rate of 4 mm/h Among biochemical parameters total protein was 72.6 g/l, albumin - 53,4%, was observed hyperlife-2-globulinemia to 12%. The level of native ceruloplasmin was above normal and was 471,5 mg/l, therefore the girl has been diagnosed with anemia of moderate severity and tissue deficit of ceruloplasmin. Despite carrying a heavy chemo treatment on a background infusion of ceruloplasmin was marked improvement in the child's condition, the correction of hemodynamic parameters. The control tests the blood for 7 weeks increased the level of hemoglobin to 118 g/l, erythrocytes to 3.6, the CPC to 0.96, among biochemical parameters returned to normal level native ceruloplasmin to 79 mg/l, but kept the camping of hyperlife-2-globulinemia to 12%. With stable hemodynamics after treatment, she was discharged home on a scheduled break under the supervision of a neurologist and pediatrician. Treatment interruptions were not. Blood transfusion was not performed.

Example # 3 illustrates alternative 2 of the proposed method is the use of ceruloplasmin in patients with purulent-septic diseases.

Statement of the case history No. 4307.

Patient L.A, 3 years. Diagnosis: Acute bronchitis, acute rhinitis, abrasions.

Ill acutely, after supercooling was observed rise in body temperature to 38.8 appeared coughing, serous at first, and then Muco-purulent discharge from the nose.

At admission were noted weakness, loss of appetite, paleness of skin, on the skin of the scalp multiple boils. In the shed - blood of the bows and the posterior pharyngeal wall. Nose was noted greenish purulent discharge. Auscultation in the lungs was carried out breathing hard, wired wheezing. In General, the analysis of blood - HB 97 g/l (anemia moderate). Er 3, CTC 0,96, Tr 357 thousand, Le 7,6, stab 12%, segmented 74%, lymphocytes 6%, monocytes 7%, ESR 70 mm/h (neutrophilia with a band shift, accelerated erythrocyte sedimentation rate (ESR). Biochemical indices of blood total protein 60 g/l, albumin - 43.7 per cent, was observed hyperlife-2-globulinemia to 20%, raising the level of haptoglobin to 22 moll (normal up to 18), ceruloplasmin to 472 mg/l (normal up to 380). Radiographically in the lungs was noted increased pulmonary pattern.

On the day of receipt boils were opened, the pus evacuated cavity washed with antiseptic solution, imposed a bandage with ointment the vegetable "levomekol. Assigned ceruloplasmin intravenous infusion 100 mg in 200 ml of 0.9% sodium chloride solution, only 7 injections and parallel to antibacterial therapy Augmentin for 7 days. Nose - interferon 1 drop 6 times a day, rinse with a solution of furacin 1:1000 - 200.0 to 6 times per day. Inside - syrup "Arisal" 1 teaspoonful 4 times a day. Body temperature returned to normal on the 3rd day from the start of therapy, increased activity, improved appetite. 4-5 day was marked complete epithelialization of the lesion. Nasal discharge was stopped on the 5th day. Auscultatory picture in the lungs were normal on the 7th day. In General, the analysis of blood HB - 110 g/L. er 3,1, CTC 0,96, Tr 440 thousand, Le 4,4, segmented 33%, basophils 3%, lymphocytes 56%, monocytes 8%, erythrocyte sedimentation rate of 12 mm/h Normalized level of ceruloplasmin to 272 mg/l, haptoglobin 5 mmol/L. Child was discharged home in good condition.

Example No. 4 illustrates a variant No. 3 of the present invention for the case of the prevention and treatment of radiation anemia after the radiation therapy.

Statement of the case history No. 6748.

Patient A.R., 10 years. Diagnosis: Fibrillar an astrocytoma of the right parieto-temporal region of the brain.

Since April 2001, headache, nausea, vomiting in the morning, was examined by a neurologist and sent for CT brain showing the volumetric process right parieto-temporal region, in June 2001 performed a craniotomy, during the operation revealed the relationship of education with the deep structures of the brain and the inability technically radical removal. Performed only by biopsy of education (histologically fibrillar astrocytoma). The postoperative period is smooth, on the 10 day, the child was transferred to the pediatric Oncology Department for radiotherapy. When translating in the General analysis of blood HB 94 g/L. er 3,12, CTC 0,9, Tr 204 thousand, Le 8000, segmented 65%, lymphocytes 27%, monocytes 4%, erythrocyte sedimentation rate of 22 mm/h Among biochemical parameters were observed hyperlife-2-globulinemia to 12%, increasing the level of ceruloplasmin up to 450 mg/L. Child was assigned a course of radiation therapy on the tumor with a total dose of 55 Gy and parallel - 1 week infusion of ceruloplasmin 100 mg in 200 ml of 0.9% sodium chloride solution for 7 weeks. In the course of treatment showed improvement of well-being, there was no nausea in the morning, increased appetite. In General, the analysis noted the following indicators: HB 137 g/l er 4,1, 1 CTC, the p 248 thousand, Le 6600, stab 1%, segmented 79%, eosinophils 3%, lymphocytes 11%, monocytes 6%, ESR 10 mm/hour, we found a decrease in the level of alpha-2-globulin to 8%, ceruloplasmin to 169 mg/L. Interruption of radiotherapy was not.

Example No. 5 illustrates a variant №1 of the present invention for the case of the prevention and treatment of posthemorrhagic anemia in surgical operations. Statement of the case history No. 11137. Sick HE, 8 years old, Diagnosis: the Doubling of the ileum. The disease is suspected by accident when my mom noticed the increase in size of the right half of the abdomen, went to a local pediatrician, and palpation of the abdomen revealed the formation in the right iliac region. Ultrasound examination was determined education in the right iliac region of about 280 tubes In total blood count showed anemia, mild (HB 100 g/l er 3,2, CTC 0,95), Tr 245 thousand, Le 10000, stab 5%, segmented 62%, eosinophils 2%, lymphocytes 21%, monocytes 10%, ESR 20 mm/h Among biochemical parameters were observed hyperlife-2-globulinemia to 13%. 2 days before the surgery, the girl started a course of intravenous injections of ceruloplasmin 100 mg in 200 ml of 0.9% solution of sodium chloride, intraoperative also introduced the drug. Operations identified malformation - doubling Podgornoe ulcer performed resection with naloge the receiving anastomosis. Intraoperative analysis of blood: HB 120 g/l er 3,3, CTC 0,99, hematocrit 35%. The need for transfusions of blood products was not. In the postoperative period the girl was also introduced ceruloplasmin in the same dose for 7 days and indicators HB was maintained at the level not less than 110 g/l, was observed correction of the level of alpha-2-globulin to 8%. Side effects with the drug is not marked.

In the clinic of pediatric surgery C on the basis of the Oncology Department of the state institution "the CLINIC" the treatment of anemia in 42 patients aged 6 months to 18 years. Of them children under 3 years amounted to 14.3%, 3-7 years - 11,9%, 8-18 years of 73.8%. Patients received intravenous infusion of the drug during the preoperative within 2 days, intraoperatively and after the intervention within 2-7 days, on the background of the septic process, during chemoradiation treatment option schemes No. 1-3 of the proposed method. Of these 10 children suffered from hematological malignancies, 9 operated on for tumours of the Central nervous system, 10 were observed bone malignancies, 5 and uninstalled abdominal tumors, 3 were treated about the soft tissue of oncological processes. In 2 patients received treatment at about oblokativshis of teracom, and another 2 about histiocytosis and rare tumors. Of the observed children 28% completed l is protome and removal of tumors of the abdominal cavity, 12% - thoracotomy to resect tumors, 16% amputation of limbs, 8% - biopsy inoperable tumors, the rest of the uninstallation of various tumors of the Central nervous system. Among the examined patients from 46% at admission marked anemia, mild (hemoglobin was 110-90 g/l), 15% - moderate anemia (hemoglobin - 89-70 g/l), 4% revealed severe anemia with hemoglobin level less than 70 g/L. In other children's tumor symptoms of intoxication, including anemicare, was absent (35%). In the days of hemiauchenia and during the subsequent infusion detoxification program patients were entered ceruloplasmin in the above mentioned doses. Compared with the control group children showed better tolerability of chemotherapy in 4 times less likely to have developed severe anemia in patients receiving infusion of the drug was required half the time for correction neutropenics complications. 50% reduction in the need for transfusions of donor blood and plasma. After extensive surgical interventions with massive blood loss has managed to avoid the development of anemia in 57% of patients, 43% were observed anemia is mild. In 100% of patients after treatment stabilized within the normal activity of serum ceruloplasmin was observed correction dysproteinemia.

Thus, applied the e ceruloplasmin in children under three variants of the proposed method allowed us to obtain high clinical results. When this reached delivered in the present invention task: ceruloplasmin is a tool that has a low cost (440 rubles), in contrast to erythropoietin used in the method prototype (more than 10,000 rubles). Also in contrast to erythropoietin ceruloplasmin is characterized by the technical ease of manufacturing. This result is achieved in that the raw material used alcoholic precipitate IY-1 in blood plasma, after receiving the homogenate conduct heat denaturation of protein impurities, conduct sorption homogenate using DEAE-Sephadex, washed sorbent from unbound proteins elute ceruloplasmin, precipitated impurities with chloroform, and ethanol precipitated the desired product ethyl alcohol, dissolve the target residue, conduct sterilizing filtration, pasteurization, filling and freeze drying of ceruloplasmin,

The introduction stage of pasteurization can improve virological safety of the drug.

The list of references.

1. Papayan A.V., Zhukov LU Anemia in children. - M - SPb.: Peter. - 2001. - 383 S.

2. Anemia in children /edited by Vigilancia. - L.: Medicine, 1983. - 360 C.

3. Heinz L., Anders O. Anemia and treatment with erythropoietin (EPO) in multiple myeloma. Anemia in cancer patients. 2002, edition 1, volume 1, pages 3-10.

4. Adelia NV, Osipova N.A., N is mcov ER, Sergeeva T. New opportunities for the prevention and correction of postoperative septic complications and multiple organ failure in Oncology. Anestesiol. and reanimate., 1997, No. 3, p.36-41.

1. The method of prevention and / or treatment of anemia in children, including the introduction of medications, characterized in that for the prevention and / or treatment of posthemorrhagic anemia in surgical operations as medications used ceruloplasmin, which is administered in a daily dose of from 50 to 200 mg depending on the age of the child, 100-200 ml of 0.9% solution of sodium chloride intravenous infusion at a rate of 40-50 drops per minute for 2 days before surgery, intraoperative and within 2-10 days after the operation.

2. The method of prevention and / or treatment of anemia in children, including the introduction of medications, characterized in that for the prevention and / or treatment of anemia with purulent-septic diseases as medications used ceruloplasmin, which is administered in a daily dose of from 50 to 200 mg depending on the age of the child, 100-200 ml of 0.9% solution of sodium chloride intravenous infusion at a rate of 40-50 drops per minute for 7-10 days along with antibiotic therapy.

3. The method of prevention and / or treatment of anemia in children is th, including the introduction of medications, characterized in that for the prevention and / or treatment of toxic and(or) radiation anemia in cancer as medications used ceruloplasmin, which is administered in a daily dose of from 50 to 200 mg depending on the age of the child, 100-200 ml of 0.9% solution of sodium chloride intravenous infusion at a rate of 40-50 drops per minute, while for the prevention and treatment of toxic anemia due to chemotherapy ceruloplasmin give chemotherapy days throughout the course, for the prevention and treatment of radiation anemia on the background of radiation therapy ceruloplasmin enter 1 time per week throughout the course of radiotherapy for prevention and treatment of toxic and radiation anemia on the background of chemoradiation therapy ceruloplasmin enter 1 time per week on the day of chemotherapy throughout the course chemoradiation treatment.

4. The method according to claims 1 to 3, characterized in that a single daily dose of ceruloplasmin depending on the age of the child is chosen as follows: children under 1 year - 50 mg, from 1 year to 12 years - 100 mg, 13-18 years - 200 mg



 

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2 tbl, 1 ex

FIELD: veterinary.

SUBSTANCE: agent is based on complex compound of colloidal iron liganded by polyoxymethylene-lauric alcohol and contains following components, mg: colloidal iron 50.0-60.0, lauric alcohol 0.1-0.3, copper 0.1-0.3, zinc 0.1-0.3, cobalt 0.1-0.3, selenium 0.001-0.005, and water to 1000. Agent can further contain 30.0-50.0 mg glucose and 0.1-0.6 mg polyvinyl alcohol.

EFFECT: enabled therapeutical and preventive efficiency at low toxicity, the same dispersity, and high stability upon storage.

3 tbl, 7 ex

FIELD: pharmaceutics, veterinary science.

SUBSTANCE: the present innovation deals with preventing and treating hypomicroelementosis in different farm and domestic animals, furred animals, and, also, for enhancing the growth in animals, and treating a number of specific diseases and, also, for maintaining microelemental composition of feedstuffs. The suggested preparation includes chelated complex of iron, manganese, zinc, copper, cobalt, selenium and iodine with organic ligand of complexone type and water. According to the innovation as a chelation ligand it contains trisodium salt of methionine succinic (α-amino-γ-methylthiobutyric-N-succinic) acid at a certain ratio of components. The innovation provides to obtain preparation in soluble form being capable to be well digested by the animal.

EFFECT: higher efficiency.

FIELD: medicine, pharmacology.

SUBSTANCE: invention relates to method for assay of optimized regimens in dosing erythropoietin (EOR). Invention proposes a system for election of one or some regimens in dosing by using pharmacokinetic/pharmacodynamic (PK/PD) as a model for assay of PK/PD pattern regimens. Then method involves selection of such regimen that provides the serum concentration of EOR exceeding its before administration for 5-30 days between administrations of EOR. Invention provides optimal applying EOR for correction of blood indices changes and treatment of diseases associated with them.

EFFECT: improved and valuable modeling method.

50 cl, 81 dwg, 2 tbl, 8 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new aminobenzophenones of the formula (I):

or their pharmaceutically acceptable salts. These compounds elicit properties of inhibitors of cytokines secretion, in particular, 1β-interleukin (IL-1β) and tumor necrosis α-factor (TNF-α) and to secretion of polymorphonuclear superoxide that are useful for treatment of inflammatory diseases, for example, skin diseases, such as psoriasis, atopic dermatitis. In the formula (I) R1 is taken among the group consisting of halogen atom, hydroxy-, mercapto-group, trifluoromethyl, amino-group, (C1-C3)-alkyl, (C2-C3)-olefinic group, (C1-C3)-alkoxy-, (C1-C3)-alkylthio-, (C1-C6)-alkylamino-group, (C1-C3)-alkoxycarbonyl, cyano-group, carbamoyl, phenyl or nitro-group under condition that when R1 means a single substitute then it at ortho-position, and when R1 means more one substitute then at least one substitute of R1 is at ortho-position; R2 means one substitute at ortho-position being indicated substitute is taken among the group consisting of (C1-C3)-alkyl, (C1-C3)-alkoxy-group; R3 means hydrogen, halogen atom, hydroxy-, mercapto-group, trifluoromethyl, amino-group, (C1-C3)-alkyl, (C2-C3)-olefinic group, (C1-C3)-alkoxy-, (C1-C3)-alkylthio-, (C1-C6)-alkylamino-group, (C1-C3)-alkoxycarbonyl, phenyl, cyano-, carboxy-group or carbamoyl; R4 means hydrogen atom or (C1-C3)-alkyl; Q means a bond or -SO2-; Y means (C1-C15)-alkyl, (C3-C10)-carbocyclic group or phenyl being each of them can be substituted optionally with one or some similar or different substitutes designated by the formula R5; R5 means halogen atom, (C1-C4)-alkyl, amino-, (C1-C3)-alkoxy-group, (C1-C3)-alkoxycarbonyl or -COOH; X means oxygen or sulfur atom. Also, invention relates to a pharmaceutical composition and to a method for treatment and/or prophylaxis of inflammatory diseases.

EFFECT: valuable medicinal properties of compounds and composition.

9 cl, 2 sch, 2 tbl, 29 ex

FIELD: medicine, phthisiology, anesthesiology.

SUBSTANCE: during the day of operation one should perform autohemotransfusion, then introduce epocrine intravenously by drops at the dosage of 50-200 U/kg patient's body weight; next day after interference one should inject epocrine subcutaneously at the dosage of 25-100 U/kg; at hematocrit level being below 35% 48 h after operation it is necessary to repeat subcutaneous injection of the above-mentioned preparation at the dosage not exceeding 50 U/kg. The present innovation favors hemopoiesis stimulation in postoperational period, that, in its turn, accelerates postoperational rehabilitation in patients of this group and enables, also, to avoid allotransfusions being dangerous because of immunoconflicting reactions.

EFFECT: higher efficiency of compensation.

1 ex, 1 tbl

The invention relates to pharmaceutical industry and relates to a method of producing iron-containing drug for the treatment and prevention of iron deficiency anemia in animals by the interaction of organic acids with gemostimuliruyuschee properties, isolated from extracts of peat, with a hydroxide of iron (11), selected from water-soluble salts of iron (11) the deposition of the alkaline solution with the subsequent laundering of water impurities

The invention relates to preparations for the prevention and treatment of Pets and farm animals, as well as to maintain the microelemental composition of the feed, and can be used in animal breeding and fur farming

The invention relates to experimental medicine, may find application in radiobiological experiments, and further in clinical practice

FIELD: medicine, oncology.

SUBSTANCE: one should carry out chemoradiation therapy at applying a cytostatic preparation followed by distance and intracavitary irradiation. Depending upon development of tumor lesion during the first 3 or 6 d it is necessary to conduct monochemotherapy only due to introducing proxiphen together with dimethyl sulfoxide at weight ratio of 4.5-5.0 : 0.5-1.5, correspondingly by applications in "Coletex" napkins. Moreover, a napkin should be pre-impregnated in 20%-dimethylsulfoxide solution and fixed with a tough vaginal tamponade by changing napkins every 24 h. Then since the 4th d or the 7th d simultaneously with application it is necessary to carry out contact irradiation and distance impact onto minor pelvis every 4-6 h at single focal dosage (SFD) being 2 Gy at 10 seances 5 times/weekly with high-activity sources of SFD 2 Gy. The innovation provides tumor regress under conditions of no therapeutic complications, thus, improving patients' quality of life.

EFFECT: higher therapy.

3 ex

FIELD: oncology.

SUBSTANCE: invention is directed, in particular, to treatment of patients with Ewing's sarcoma and osteogenic sarcoma at different stages of malignant process. Method comprises chemotherapy and beam therapy. Samples of venous blood are taken from children in age of 5 to 12 years in amounts not larger than 5% of the total volume of circulating blood per 1 introduced dose of chemical preparation and, from adolescents and young persons, in amount of 200 ml. Then 4 courses of polychemotherapy are fulfilled with autoblood according to standard treatment schemes for given diseases, taking into account stages of disease, in recommended doses. Between 2nd and 3rd chemotherapy courses, radiotherapy is fulfilled on metastatic focuses in lungs. After 4 courses of induction autohemo-chemotherapy, local therapy on the primary focus (radiotherapy and/or surgical treatment) is fulfilled and also radiotherapy on metastatic focuses in other bones, after which follows consolidation involving chemical preparation of the second line.

EFFECT: improved remote results of treatment , suppressed metastatic focuses, reduced tumor dimensions, and weakened toxic manifestations of therapy.

2 ex

FIELD: medicine.

SUBSTANCE: the present innovation deals with measuring radioactivity in alive organisms and could be applied for detecting really absorbed dosage under conditions of intra-operational impact. The method suggested includes detecting clinical volume for the target of radiation impact including the volume of healthy tissues to be subjected for radiation impact, developing the plan of radiation impact based upon data obtained with the help of tissue-equivalent phantoms, location in interest sites of clinical volume of sterilized separate fragments of dosimetric device being the matrix of functional units and designed as thermoluminescent detectors being hermetically isolated at the distance of 10 mm between their edges and fixed between the layers of flexible biocompatible material, registering the location of detectors, performing the séance for intra-operational radiation therapy followed by removing the fragments of dosimetric device out of target's volume. Information should be read from thermoluminescent detectors.

EFFECT: higher accuracy of measuring.

1 cl, 1 dwg, 1 ex

FIELD: medicine.

SUBSTANCE: the present innovation deals with treating malignant tumors of central bronchi and trachea due to argonoplasmatic recanalization of tracheal lumen and/or bronchi, at power being 60-90 W followed by brachitherapy at source's trajectory length being 5-20 cm, pace of 5 mm and the depth of reference isodose being 10 mm against the source. Moreover, one should move applicator above and below the tumor ranged 1-3 cm to apply the dose ranged 14-28 Gy once weekly per 7 Gy. Additionally, one should carry out distance radiation therapy 5 times weekly per 1-2 Gy up to total focal dose of 30-40 Gy. The present innovation enables to highly increase the passability of respiratory tract in case of malignant stenosis and prevent the development of their relapse.

EFFECT: higher efficiency of therapy.

3 ex

FIELD: medicine, neurooncology.

SUBSTANCE: one should carry out chemotherapy and irradiation till radical dosage. Moreover, 2-3 d before the onset of radiation therapy and during the whole course of irradiation one should indicate the intake of indometacin at daily dosage being 300 mg, and 8-14 d before the end of therapy course or the stage of radiation therapy it is necessary to conduct chemotherapeutic cycle with vincristine at total dosage being 4 mG and lomustine at total dosage 160-240 mg. At performing a split course of irradiation the intake of indometacin should be indicated between the stages. The innovation enables to increase radio sensitivity of malignant tumor, suppress angiogenesis, proliferative activity and increased cytotoxic activity of chemopreparations.

EFFECT: higher efficiency of therapy.

1 cl, 3 ex

FIELD: medicine, oncology, gynecology.

SUBSTANCE: method involves external irradiation and using chemopreparations combined with autoplasma. External irradiation in the dose 2 Gr is carried out from 1 to 4 day of treatment followed by intravenous administration of cisplatin on 5 day in the dose 10 mg with 250 ml of physiological solution. On the following day 10 ml of autoplasma incubated with 10 mg of cisplatin is administrated by paratumoral route by right and left of tumor into paravaginal cellular tissue and by intratumoral route into projection of cervical channel. Blood cellular elements are incubated with 600 mg of cyclophosphane and reinfused by intravenous drop route. Effects are repeated in indicated sequence once per a week, 4 times per treatment course. Method provides increasing percent of tumor regression due to the complex effect on tumor, enhancing the topical concentration of cytostatic drug and prolongation of its contact in malignant growth zone, and providing radiosensibilizing effect in diminishing the general toxic effect of therapy. Invention can be used in treatment of patients with topically disseminated forms of uterus cervix cancer at the stage T3NxM0.

EFFECT: improved and enhanced treatment method.

1 ex

FIELD: medicine, oncourology.

SUBSTANCE: the present innovation deals with conservative treatment of patients with malignant prostatic tumor at different stages. The method includes testicular enucleation, introduction of anti-tumor chemopreparations and radiation therapy. Moreover, in the onset of radiation therapy one should introduce 25 mg Cisplatin incubated with 10 ml patient's plasma into both prostatic lobes and paraprostatic fiber from the right and from the left. At achieving a focal dosage of 20 Gy one should repeat introduction of chemopreparation in similar dosage, and radiation therapy should be continued up to total focal dosage of 40 Gy. The innovation enables to decrease tumor sizes, side manifestations of radiation therapy at decreasing radiation loading and improve patient's life quality due to mitigating the urination.

EFFECT: higher efficiency of therapy.

1 ex

FIELD: medicine, oncology.

SUBSTANCE: before irradiation it is necessary to cool the tumor to achieve the temperature of freezing at clinically detectable border between the tumor and healthy tissue to perform irradiation directly after natural tissue defrosting with a single focal dosage (SFD) being 2-2.5 Gy daily for 5 d a week at 2-d-long interval to achieve total focal dosage (TFD) of 60-65 Gy. Moreover, the area of healthy tissue should be protected with a shielding applicator - a lead plate - during irradiation. The present innovation enables to maximally keep anatomical relief and function of local tissues.

EFFECT: higher efficiency of therapy.

1 cl, 4 ex

FIELD: medicine, oncology.

SUBSTANCE: the method deals with applying chemopreparations incubated with autolymph and radiation therapy. Lymph taken out of patient's thoracic duct should be centrifuged for 30 min at 2200 rot./min, lymphatic plasma should be taken and frozen at -40 C, lymphatic formic elements should be incubated in a thermostat at 37 C for 1 h together with chemopreparations by a certain scheme to be reinfused for a patient intravenously by drops according to the given scheme. Then, 2 wk later, one should perform therapy with a split course of distance gammatherapy at single focal dosage (SFD) of 4 Gy. At the first stage one should apply per 2 Gy twice daily at 4-5-h-long interval 5 times weekly, at achieving focal dosage of 28 Gy it is necessary to have a week-long interval. Then radiation therapy should be continued but SFD of 4 Gy should be applied at once. One should fulfill 3 fractions of irradiation per a week, there are 6 fractions during the second stage, totally. Total focal dosage (TFD) per the whole course of irradiation corresponds to 52 Gy. About 4 wk after radiation therapy one should defrost lymphatic plasma to incubate it with the same chemopreparations in a thermostat at 37 C for 1 h to be then reinfused for a patient intravenously by drops. The method enables to decrease tumor volume and tumor process metastasing without any operative interference.

EFFECT: higher efficiency of therapy.

1 ex

FIELD: experimental medicine, oncology, biology.

SUBSTANCE: invention relates to a method for inhibition of tumor growth using radiation therapy as ionizing radiation with additional administration of mixture of octa-4,5-carboxyphthalocyanine sodium cobalt salt or oxocobalamine with sodium ascorbate in the ratio = (1:10)-(1:30). Method of combined using irradiation and indicated mixture of substances provides enhancing the effectiveness of anti-tumor treatment resulting to 70-100% recovery of experimental animals and reducing radiation loading and toxicity.

EFFECT: improved method for inhibition.

2 tbl, 3 dwg, 3 ex

FIELD: medicine.

SUBSTANCE: method involves administering basic therapy and intrauterine instillations with proteolytic enzyme of profesyme at a dose equal to 1 ml per 1 cm2 of uterus wound surface calculated from ultrasonic scanning data.

EFFECT: reduced fever period; accelerated intoxication symptom alleviation; reduced risk of reproductive complications.

1 tbl

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