MD501Z - Method for prophylaxis of postradiation complications in oncologic diseases - Google Patents
Method for prophylaxis of postradiation complications in oncologic diseases Download PDFInfo
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- MD501Z MD501Z MDS20110122A MDS20110122A MD501Z MD 501 Z MD501 Z MD 501Z MD S20110122 A MDS20110122 A MD S20110122A MD S20110122 A MDS20110122 A MD S20110122A MD 501 Z MD501 Z MD 501Z
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Abstract
Description
Invenţia se referă la medicină, şi anume la tratamentul radioterapeutic în oncologie. The invention relates to medicine, namely to radiotherapeutic treatment in oncology.
În ultimii ani se observă o creştere a morbidităţii oncologice şi respectiv se modifică şi se propun noi metode de tratament al maladiilor în cauză. Optimizarea tratamentului antitumoral se desfăşoară în direcţia integrării diferitelor metode de tratament, combinării metodelor de radioterapie cu chimioterapie şi tratament chirurgical. Creşte considerabil rolul metodelor de radioterapie, care se perfecţionează datorită acumulării de experienţă în tratamentul acestor maladii, iar pacienţii le preferă pentru a evita metodele chirurgicale de tratament [1, 2]. In recent years, there has been an increase in oncological morbidity, and new methods of treatment of these diseases have been proposed and modified. Optimization of antitumor treatment is carried out in the direction of integrating various treatment methods, combining radiotherapy methods with chemotherapy and surgical treatment. The role of radiotherapy methods is increasing significantly, which is being improved due to the accumulation of experience in the treatment of these diseases, and patients prefer them to avoid surgical methods of treatment [1, 2].
În pofida perfecţionării metodelor de radioterapie, aplicarea lor, ca şi mai înainte, este însoţită de complicaţii, uneori grave, care impun întreruperea cursului de radioterapie sau renunţarea la el. Despite the improvement of radiotherapy methods, their application, as before, is accompanied by complications, sometimes serious, which require the interruption of the radiotherapy course or its abandonment.
Complicaţiile survenite în urma radioterapiei depind de localizarea tumorii, tipul de iradiere, volumul tumoral, factorii timp, vârstă, stare clinică a pacientului, maladiile asociate. Complications arising from radiotherapy depend on the location of the tumor, the type of irradiation, the tumor volume, time factors, age, clinical condition of the patient, and associated diseases.
După timpul apariţiei lor, complicaţiile menţionate pot fi divizate în: acute (apar în primele zile ale iradierii), precoce (apar după 7…10 zile de radioterapie) şi tardive (apar după câteva săptămâni sau chiar în timp de 6 luni după terminarea cursului de radioterapie). According to the time of their occurrence, the mentioned complications can be divided into: acute (occur in the first days of irradiation), early (occur after 7…10 days of radiotherapy) and late (occur after a few weeks or even 6 months after the end of the radiotherapy course).
Complicaţiile acute se manifestă sub diferite forme: stare de rău de raze - în primele zile de radioterapie se instalează astenie, anorexie, cefalee, radiodermatită acută (hiperemia cutanată, depilare), radiomucită acută (hiperemia şi tumefierea mucoaselor cu dureri bucale, greaţă şi vărsături, diaree, dureri abdominale). Acute complications manifest in various forms: radiation sickness - in the first days of radiotherapy, asthenia, anorexia, headache, acute radiodermatitis (skin hyperemia, hair loss), acute radiomucitis (hyperemia and swelling of the mucous membranes with mouth pain, nausea and vomiting, diarrhea, abdominal pain) occur.
Complicaţiile precoce pot fi: căderea părului, astenie fizică moderată şi paloarea tegumentelor (datorită anemiei), risc crescut de infecţii (prin scăderea numărului de leucocite), sângerări diverse (prin scăderea numărului de trombocite). Early complications can be: hair loss, moderate physical weakness and pale skin (due to anemia), increased risk of infections (due to decreased leukocyte count), various bleeding (due to decreased platelet count).
Efectele secundare tardive: fibroză, radiodermatită cronică (piele fină, uscată, cuperoasă), ulceraţii, fistule, insuficienţe de organe (pentru plămâni - fibroză, pentru măduva osoasă - aplazie, pentru rinichi - nefrită, inimă - pericardită, ficat - hepatită, întârziere a creşterii la copii etc). O categorie particulară de efecte secundare sunt cele mutagene şi cancerigene. Radioterapiei îi este incriminată apariţia unor cancere secundare ce apar după ani de zile de la iradiere (leucemii, mielodisplazii, limfoame, sarcoame) [1, 2]. Late side effects: fibrosis, chronic radiodermatitis (fine, dry, cupero-like skin), ulcerations, fistulas, organ failure (for lungs - fibrosis, for bone marrow - aplasia, for kidneys - nephritis, heart - pericarditis, liver - hepatitis, growth retardation in children, etc.). A particular category of side effects are mutagenic and carcinogenic ones. Radiotherapy is incriminated with the appearance of secondary cancers that appear years after irradiation (leukemias, myelodysplasias, lymphomas, sarcomas) [1, 2].
Este cunoscută metoda de diminuare a complicaţiilor survenite în urma radioterapiei prin utilizarea preparatului Canefron H la pacienţii oncologici cu tumori ale organelor bazinului mic [3]. The method of reducing complications arising from radiotherapy by using the preparation Canephron H in oncological patients with tumors of the pelvic organs is known [3].
Dezavantajele acestei metode constau în posibilitatea apariţiei reacţiilor alergice la componenţii preparatului şi utilizarea limitată a lui [3]. The disadvantages of this method are the possibility of allergic reactions to the components of the preparation and its limited use [3].
Problema pe care o rezolvă invenţia constă în extinderea arsenalului de metode utilizate pentru prevenirea complicaţiilor postradiante la bolnavii oncologici. The problem that the invention solves consists in expanding the arsenal of methods used to prevent post-radiation complications in oncological patients.
Esenţa invenţiei constă în aceea că o dată în zi, îndată după mese, timp de 15 zile de la începutul curei de radioterapie, se administrează intramuscular 5 mL soluţie de 5% de acid ascorbic (vitamina C) şi peroral o capsulă (33000 UI) de retinol (vitamina A), o capsulă (0,2 g) de tocoferol (vitamina E) şi un comprimat (0,2 g) de metiluracil. Concomitent se administrează peroral ulei din miez de nucă (Juglans Regia), câte o lingură de masă (15 mL) de 2 ori pe zi, începând cu 2…3 zile înainte de iniţierea curei de radioterapie şi în continuare pe tot parcursul ei. The essence of the invention consists in that once a day, immediately after meals, for 15 days from the beginning of the radiotherapy course, 5 mL of 5% ascorbic acid (vitamin C) solution is administered intramuscularly and peroral one capsule (33000 IU) of retinol (vitamin A), one capsule (0.2 g) of tocopherol (vitamin E) and one tablet (0.2 g) of methyluracil. At the same time, walnut kernel oil (Juglans Regia) is administered peroral, one tablespoon (15 mL) 2 times a day, starting 2...3 days before the initiation of the radiotherapy course and continuing throughout its course.
Rezultatul constă în diminuarea complicaţiilor postradiante locale şi generale la bolnavii oncologici. The result is the reduction of local and general post-radiation complications in oncological patients.
Avantajele metodei constau în faptul că utilizarea uleiului din miez de nucă înainte de cursul de radioterapie, datorită proprietăţilor sale, previne apariţia complicaţiilor acute survenite în urma radioterapiei, iar utilizarea lui în asociere cu vitamine şi uracil, în timpul cursului de radioterapie, diminuează semnificativ gradul de manifestare a complicaţiilor precoce ale iradierii. Metoda propusă diminuează considerabil gradul de manifestare a complicaţiilor survenite în urma radioterapiei şi permite suportarea cursului întreg. The advantages of the method are that the use of walnut kernel oil before the course of radiotherapy, due to its properties, prevents the occurrence of acute complications arising from radiotherapy, and its use in combination with vitamins and uracil, during the course of radiotherapy, significantly reduces the degree of manifestation of early complications of irradiation. The proposed method considerably reduces the degree of manifestation of complications arising from radiotherapy and allows to endure the entire course.
Metoda propusă se efectuează în felul următor: o dată pe zi, îndată după mese, timp de 15 zile de la începutul curei de radioterapie, se administrează intramuscular 5 mL soluţie de 5% de acid ascorbic şi peroral o capsulă (33000 UI) de retinol, o capsulă (0,2 g) de tocoferol şi un comprimat (0,2 g) de metiluracil. Totodată, începând cu 2…3 zile înainte de iniţierea curei de radioterapie, precum şi pe tot parcursul ei, se administrează peroral ulei din miez de nucă (Juglans Regia), câte o lingură de masă (15 mL) de 2 ori pe zi. The proposed method is carried out as follows: once a day, immediately after meals, for 15 days from the beginning of the radiotherapy course, 5 mL of 5% ascorbic acid solution is administered intramuscularly and perorally one capsule (33000 IU) of retinol, one capsule (0.2 g) of tocopherol and one tablet (0.2 g) of methyluracil. At the same time, starting 2…3 days before the initiation of the radiotherapy course, as well as throughout it, walnut kernel oil (Juglans Regia) is administered perorally, one tablespoon (15 mL) 2 times a day.
Exemplu de studiu clinic Example of a clinical study
Caracteristicile radioprotectoare ale metodei propuse au fost studiate pe pacienţi oncologici supuşi radioterapiei în Secţia de Radioterapie a Institutului Oncologic. Scopul studiului a constat în aprecierea eficacităţii metodei cu utilizarea uleiului din miez de nucă pentru profilaxia şi tratamentul complicaţiilor survenite în urma radioterapiei. The radioprotective characteristics of the proposed method were studied on oncological patients undergoing radiotherapy in the Radiotherapy Department of the Oncological Institute. The aim of the study was to assess the effectiveness of the method using walnut kernel oil for the prophylaxis and treatment of complications arising from radiotherapy.
Material şi metode Material and methods
Studiul a fost efectuat asupra a 30 de pacienţi cu cancer al regiunii cap şi gât (preponderent cu cancer laringian şi al regiunii nazofaringelui) supuşi radioterapiei. Vârsta pacienţilor a variat de la 40 până la 68 ani (în medie 52 ani). Pacienţii au fost repartizaţi în 3 grupe. Grupul de bază a fost constituit din 10 pacienţi, la care radioterapia a fost efectuată pe fundalul aplicării metodei propuse. Grupul de referinţă a utilizat aceleaşi preparate, cu excepţia uleiului din miez de nucă, iar grupul de control, format din 10 pacienţi, a fost supus radioterapiei fără aplicarea metodelor de profilaxie a cursului de radioterapie. The study was conducted on 30 patients with head and neck cancer (mainly laryngeal and nasopharyngeal cancer) undergoing radiotherapy. The patients' age ranged from 40 to 68 years (average 52 years). The patients were divided into 3 groups. The base group consisted of 10 patients, who underwent radiotherapy against the background of the proposed method. The reference group used the same preparations, except for walnut kernel oil, and the control group, consisting of 10 patients, underwent radiotherapy without the use of radiotherapy prophylaxis methods.
Radioterapia a fost efectuată cu ajutorul instalaţiei TERABALT (ca sursă a servit Cobaltul-60). Durata şedinţelor a constituit în medie 1…1,6 min (cu o frecvenţă de 60…80 impulsuri pe şedinţă). Radiotherapy was performed using the TERABALT device (Cobalt-60 served as the source). The duration of the sessions was on average 1…1.6 min (with a frequency of 60…80 pulses per session).
Pacienţii cu cancer laringian au fost supuşi la 21 şedinţe de radioterapie la distanţă. Patients with laryngeal cancer underwent 21 remote radiotherapy sessions.
Pe parcursul perioadei de radioterapie pacienţii au fost supuşi supravegherii zilnice cu colectarea analizei generale a sângelui (la începutul şi sfârşitul radioterapiei). During the radiotherapy period, patients were subjected to daily monitoring with collection of general blood tests (at the beginning and end of radiotherapy).
Aprecierea eficacităţii metodei propuse a fost efectuată în funcţie de gradul de manifestare a afectării mucoaselor şi pielii regiunii supuse radioterapiei. The assessment of the effectiveness of the proposed method was carried out depending on the degree of manifestation of the damage to the mucous membranes and skin of the region subjected to radiotherapy.
Pentru aprecierea rezultatelor au fost selectaţi următorii indici: The following indices were selected to assess the results:
- timpul apariţiei simptomelor afectării mucoasei cavităţii bucale (în funcţie de numărul de şedinţe din cura de radioterapie); - the time of appearance of symptoms of damage to the oral mucosa (depending on the number of sessions in the radiotherapy course);
- nivelul de exprimare a simptomelor. - the level of expression of symptoms.
Gradul de exprimare a complicaţiilor postradiante precoce din partea regiunilor supuse iradierii - hiperemia şi edemul mucoasei cavităţii bucale, a fost apreciat conform următoarei scheme: The degree of expression of early post-radiation complications from the regions subjected to irradiation - hyperemia and edema of the oral mucosa, was assessed according to the following scheme:
- gradul I (+) - hiperemie şi edem neesenţial; - grade I (+) - hyperemia and non-essential edema;
- gradul II (++) - hiperemie şi edem al mucoasei de intensitate mică, fără dureri în cazul masticării; - grade II (++) - low-intensity hyperemia and edema of the mucosa, without pain when chewing;
- gradul III (+++) - hiperemie şi edem al mucoasei de intensitate medie, cu dureri numai în cazul masticării, fără stoparea radioterapiei; - grade III (+++) - hyperemia and edema of the mucosa of medium intensity, with pain only when chewing, without stopping radiotherapy;
- gradul IV (++++) - hiperemie şi edem al mucoasei foarte exprimate, care provoacă o dereglare gravă a procesului de masticare, cu dureri insuportabile, care a impus stoparea şedinţelor de radioterapie. - grade IV (++++) - very pronounced hyperemia and edema of the mucosa, which causes a serious disruption of the chewing process, with unbearable pain, which forced the cessation of radiotherapy sessions.
De asemenea, au fost înregistrate nivelul leucocitemiei şi VSH din analiza generală a sângelui. The leukocyte count and ESR levels from the general blood test were also recorded.
Rezultatele studiului Study results
Aplicarea metodei propuse de profilaxie a complicaţiilor postradiante a demonstrat o eficacitate înaltă în profilaxia complicaţiilor mucoasei cavităţii bucale şi organelor adiacente la pacienţii cu cancer laringian supuşi tratamentului radiologic. Eficacitatea aplicării ei este confirmată prin faptul că complicaţiile în urma radioterapiei la pacienţii pentru care s-a aplicat această metodă apar cu 8…9 zile mai târziu comparativ cu cei pentru care metoda nu s-a aplicat, şi cu 2…3 zile mai târziu comparativ cu cei care au administrat aceleaşi preparate, cu excepţia uleiului din miez de nucă (tab. 1). The application of the proposed method of prophylaxis of postradiation complications has demonstrated high efficacy in the prophylaxis of complications of the oral mucosa and adjacent organs in patients with laryngeal cancer undergoing radiation treatment. The efficacy of its application is confirmed by the fact that complications following radiotherapy in patients for whom this method was applied appear 8…9 days later compared to those for whom the method was not applied, and 2…3 days later compared to those who administered the same preparations, except for walnut kernel oil (Table 1).
Tabelul 1 Table 1
Indici şi simptome Grupul martor (n=10) Crupul de referinţă (n=10) Grupul de bază (n=10) Timpul apariţiei simptomelor (numărul de cure de radioterapie) 5±1,6 11±1,3 14±1,2 Nivelul de exprimare a durerilor permanente puternice periodice de intensitate medie periodice neesenţiale Apariţia epitelitei şi depunerilor de exsudat fibrinos focare multiple unice lipsăIndices and symptoms Control group (n=10) Reference group (n=10) Baseline group (n=10) Time of onset of symptoms (number of radiotherapy courses) 5±1.6 11±1.3 14±1.2 Level of expression of pain permanent strong periodic of medium intensity periodic non-essential Appearance of epithelitis and deposits of fibrinous exudate multiple single foci absent
De asemenea, din tabel se observă o diminuare a intensităţii şi durabilităţii durerilor cu lipsa epitelitei şi depunerilor de exsudat fibrinos pe mucoasa cavităţii bucale la pacienţii din grupul de bază, care pe perioada radioterapiei au utilizat şi ulei din miez de nucă. La pacienţii, pentru care s-au administrat în timpul radioterapiei numai preparatele menţionate, dar fără ulei din miez de nucă, au fost depistate aproximativ la toţi depuneri de exsudat fibrinos, după gradul de exprimare au fost puţin mai superficiale comparativ cu manifestările respective la pacienţii din grupul martor. Respectiv, din punct de vedere al gradului de protecţie a mucoasei cavităţii bucale, conform rezultatelor obţinute, mai eficientă este metoda de profilaxie a complicaţiilor postradiante, care include şi ulei din miez de nucă. Also, the table shows a decrease in the intensity and duration of pain with the absence of epithelitis and fibrinous exudate deposits on the oral mucosa in patients from the base group, who also used walnut kernel oil during radiotherapy. In patients, for whom only the aforementioned preparations were administered during radiotherapy, but without walnut kernel oil, fibrinous exudate deposits were detected in almost all of them, according to the degree of expression they were slightly more superficial compared to the respective manifestations in patients from the control group. Accordingly, from the point of view of the degree of protection of the oral mucosa, according to the results obtained, the method of prophylaxis of postradiation complications, which also includes walnut kernel oil, is more effective.
Gradele de dezvoltare a hiperemiei şi edemului mucoasei cavităţii bucale la pacienţii cu cancer laringian sunt prezentate în tab. 2. The degrees of development of hyperemia and edema of the oral mucosa in patients with laryngeal cancer are presented in Table 2.
Tabelul 2 Table 2
Pacienţi cu cancer faringian Hiperemia mucoasei cavităţii bucale Edemul mucoasei cavităţii bucale Pacienţi din grupul de bază 1 + + 2 + + 3 ++ + 4 ++ + 5 + + 6 ++ + 7 + + 8 ++ + 9 + + 10 ++ + Pacienţi din grupul de control 1 ++++ +++ 2 +++ +++ 3 ++++ ++++ 4 +++ +++ 5 +++ +++ 6 +++ +++ 7 +++ +++ 8 +++ +++ 9 ++++ ++++ 10 +++ +++ Pacienţi din grupul de referinţă 1 ++ ++ 2 ++ ++ 3 ++ ++ 4 ++ ++ 5 ++ ++ 6 ++ ++ 7 ++ ++ 8 ++ ++ 9 ++ ++ 10 ++ ++Patients with pharyngeal cancer Oral mucosa hyperemia Oral mucosa edema Patients in the base group 1 + + 2 + + 3 ++ + 4 ++ + 5 + + 6 ++ + 7 + + 8 ++ + 9 + + 10 ++ + Patients in the control group 1 ++++ +++ 2 +++ +++ 3 ++++ ++++ 4 +++ +++ 5 +++ +++ 6 +++ +++ 7 +++ +++ 8 +++ +++ 9 ++++ ++++ 10 +++ +++ Patients in the reference group 1 ++ ++ 2 ++ ++ 3 ++ ++ 4 ++ ++ 5 ++ ++ 6 ++ ++ 7 ++ ++ 8 ++ ++ 9 ++ ++ 10 ++ ++
Din tabel se observă o diminuare a gradului de exprimare a edemului mucoasei cavităţii bucale la pacienţii supuşi radioterapiei regiunii date din grupul de bază, care suplimentar au utilizat pe parcursul curei de radioterapie ulei din miez de nucă. Nivelul edemului la toţi pacienţii din acest grup a fost stabilit de gradul I, caracterizat ca un edem de intensitate mică neesenţial. Rezultate similare de diminuare a gradelor de exprimare au fost obţinute şi în cazul hiperemiei mucoasei cavităţii bucale. Hiperemia cavităţii bucale la 5 pacienţi din grupul de bază a fost apreciată de gradul I şi de gradul II la ceilalţi 5 pacienţi. The table shows a decrease in the degree of expression of edema of the oral mucosa in patients undergoing radiotherapy to the given region in the base group, who additionally used walnut kernel oil during the course of radiotherapy. The level of edema in all patients in this group was established as grade I, characterized as a non-essential low-intensity edema. Similar results of the decrease in the degrees of expression were obtained in the case of hyperemia of the oral mucosa. Hyperemia of the oral cavity in 5 patients in the base group was assessed as grade I and grade II in the other 5 patients.
La pacienţii din grupul de control gradele de exprimare a edemului şi hiperemiei mucoasei sunt mult mai exprimate. Edemul şi hiperemia mucoasei la 7 pacienţi din acest grup au fost stabilite de gradul III, caracterizate ca un edem şi hiperemie de intensitate medie cu dureri numai în cazul masticării, fără stoparea cursului de radioterapie. Trei pacienţi au fost nevoiţi să stopeze pe o perioadă de timp cursul de radioterapie din cauza hiperemiei şi edemului mucoasei foarte exprimate, care au provocat o dereglare gravă a procesului de masticare cu dureri insuportabile. In the patients in the control group, the degrees of mucosal edema and hyperemia were much more pronounced. Edema and hyperemia of the mucosa in 7 patients in this group were determined as grade III, characterized as edema and hyperemia of moderate intensity with pain only during chewing, without stopping the course of radiotherapy. Three patients had to stop the course of radiotherapy for a period of time due to very pronounced mucosal edema and hyperemia, which caused a serious disruption of the chewing process with unbearable pain.
Rezultate intermediare au fost obţinute la pacienţii, care au utilizat pe perioada cursului de radioterapie metoda de profilaxie, fără utilizarea asociată a uleiului din miez de nucă. La toţi pacienţii în medie a fost stabilit gradul II (++) de manifestare, caracterizat printr-o hiperemie şi edem al mucoasei de intensitate mică fără dureri în cazul masticării. Intermediate results were obtained in patients who used the prophylaxis method during the course of radiotherapy, without the associated use of walnut kernel oil. In all patients, on average, grade II (++) of manifestation was established, characterized by low-intensity hyperemia and edema of the mucosa without pain when chewing.
Rezultatele determinării numărului de leucocite, a nivelului VSH la pacienţii supuşi studiului au fost prelucrate statistic şi sunt prezentate în tab. 3. The results of determining the number of leukocytes and the ESR level in the patients undergoing the study were statistically processed and are presented in Table 3.
Tabelul 3 Table 3
Indicii hematologici Grupul martor (n=10) Grupul de referinţă (n=10) Grupul de bază (n=10) Nivelul leucocitelor în sângele periferic 19 ± 1,4 11 ± 1,2 5 ± 1,1 Nivelul VSH-ului 15 ± 1,3 8 ± 1,2 4 ± 1,2Hematological indices Control group (n=10) Reference group (n=10) Baseline group (n=10) Leukocyte level in peripheral blood 19 ± 1.4 11 ± 1.2 5 ± 1.1 ESR level 15 ± 1.3 8 ± 1.2 4 ± 1.2
Conform rezultatelor din tabel se determină o diminuare esenţială a numărului de leucocite şi nivelului VSH la pacienţii din grupul de bază, pentru care pe perioada cursului de radioterapie s-a aplicat metoda propusă. According to the results in the table, an essential decrease in the number of leukocytes and the ESR level is determined in patients from the base group, for whom the proposed method was applied during the course of radiotherapy.
1. Ролик И.С. Биологические препараты в реабилитации больных раком: руководство для врачей. Москва, Арнебия, 2000 1. Ролик И.С. Biological preparations in the rehabilitation of cancer patients: instructions for doctors. Moscow, Arnebiya, 2000
2. Справочник Видаль. Лекарственные препараты в России, издание 15-е, 2009 2. Справочник Видаль. Medicinal preparations in Russia, edition 15, 2009
3. Каприн А.Д., Семин А.В., Костин А.А. Эффективность препарата "Канефрон Н" у онкологически больных, получающих лучевую терапию на органы малого таза. Человек и лекарство, №5, том 15, 2007 3. Kaprin A.D., Semin A.V., Kostin A.A. Effectiveness of the preparation "Kanefron H" in oncological patients receiving radiation therapy on pelvic organs. Man and medicine, №5, volume 15, 2007
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| MD2324G2 (en) * | 2003-07-25 | 2004-07-31 | Ион ИЛИЧУК | Metabolism regulating medicament |
| EA201001000A1 (en) * | 2010-04-19 | 2011-10-31 | Алмагуль Тулеуовна Маншарипова | ANTIOXIDANT MEANS OIL BALSAM "JEWELAX" |
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| MD2324G2 (en) * | 2003-07-25 | 2004-07-31 | Ион ИЛИЧУК | Metabolism regulating medicament |
| EA201001000A1 (en) * | 2010-04-19 | 2011-10-31 | Алмагуль Тулеуовна Маншарипова | ANTIOXIDANT MEANS OIL BALSAM "JEWELAX" |
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| Title |
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| Каприн А.Д., Семин А.В., Костин А.А. Эффективность препарата "Канефрон Н" у онкологически больных, получающих лучевую терапию на органы малого таза. Человек и лекарство, №5, том 15, 2007 * |
| Ролик И.С. Биологические препараты в реабилитации больных раком: руководство для врачей. Москва, Арнебия, 2000 * |
| Справочник Видаль. Лекарственные препараты в России, издание 15-е, 2009 * |
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