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B950d65c8231ff7dad32f921e77f Пятигорский медико-фармацевтический институт – филиал государственного бюджетного образовательного учреждения высшего профессионального образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской Федерации На правах рукописи ФЕДОТОВА ВИКТОРИЯ ВЛАДИМИРОВНА Фармакогностическое изучение золотарника кавказского (Solidago caucasica Kem.–Nath.) 14.04.02 – фармацевтическая химия, фармакогнозия ДИССЕРТАЦИЯ на соискание ученой степени кандидата фармацевтических наук НАУЧНЫЙ РУКОВОДИТЕЛЬ КОНОВАЛОВ Д.А. ДОКТОР ФАРМАЦЕВТИЧЕСКИХ НАУК, ПРОФЕССОР ПЯТИГОРСК – 2014 2 ОГЛАВЛЕНИЕ СПИСОК СОКРАЩЕНИЙ ...................................................................................... 6 ВВЕДЕНИЕ .............................................................................................................. 7 ГЛАВА 1 ФАРМАКОГНОСТИЧЕСКАЯ ХАРАКТЕРИСТИКА ВИДОВ РОДА ЗОЛОТАРНИК ....................................................................................................... 13 1.1 История и распространение видов рода Золотарник...................................... 13 1.2 Ботаническая характеристика видов рода Золотарник .................................. 16 1.3 Систематическое положение рода Золотарник .............................................. 17 1.4 Химический состав изученных видов рода Золотарник ............................... 18 1.5 Использование сырья видов рода Золотарник ................................................ 22 Выводы по обзору литературы .............................................................................. 29 ГЛАВА 2 ОБЪЕКТЫ И МЕТОДЫ ИССЛЕДОВАНИЯ ....................................... 30 2.1 Объекты исследования ..................................................................................... 30 2.2 Методы исследования ...................................................................................... 31 2.2.1 Химические реакции ...................................................................................... 31 2.2.2 Хроматографические методы исследования ................................................. 32 2.2.3 Спектральные методы .................................................................................... 33 2.2.4 Титриметрические методы ............................................................................. 34 2.2.5 Гравиметрические методы ............................................................................. 34 2.2.6 Ресурсоведческие исследования .................................................................... 34 2.2.7 Фармакологические методы исследования ................................................... 35 2.2.8 Отбор проб для анализа ................................................................................. 36 2.2.9 Методы макро– и микроскопического анализа сырья ................................. 36 2.2.10 Определение числовых показателей ........................................................... 37 2.2.11 Валидация методики количественного определения ................................. 37 2.2.12 Микробиологическая чистота ...................................................................... 37 2.2.13 Определение сроков годности ..................................................................... 37 2.2.14 Методы статистической обработки ............................................................. 37 3 ГЛАВА 3 ПРЕДВАРИТЕЛЬНЫЕ РЕСУРСОВЕДЧЕСКИЕ ИССЛЕДОВАНИЯ ЗОЛОТАРНИКА КАВКАЗСКОГО И ИЗУЧЕНИЕ ВОЗМОЖНОСТЕЙ ВВЕДЕНИЯ ЕГО В КУЛЬТУРУ ........................................................................... 38 3.1 Определение урожайности травы золотарника кавказского.......................... 38 3.2 Расчет объема ежегодных заготовок ............................................................... 39 3.3 Исследования по введению золотарника кавказского в культуру ................. 41 Выводы по главе..................................................................................................... 45 ГЛАВА 4 МОРФОЛОГИЧЕСКОЕ И АНАТОМО–ДИАГНОСТИЧЕСКОЕ ИЗУЧЕНИЕ ТРАВЫ И КОРНЕВИЩ С КОРНЯМИ ЗОЛОТАРНИКА КАВКАЗСКОГО..................................................................................................... 46 4.1 Морфологическая характеристика «Золотарника кавказского травы» ......... 46 4.2 Анатомическое строение листа ....................................................................... 47 4.2.1 Строение листа с поверхности ....................................................................... 47 4.2.2 Строение листа на поперечном срезе ............................................................ 50 4.3 Анатомическое строение стебля ...................................................................... 52 4.3.1 Строение стебля с поверхности ..................................................................... 52 4.3.2 Строение стебля на поперечном срезе .......................................................... 53 4.3.3 Строение стебля на продольном срезе .......................................................... 57 4.4 Анатомическое строение цветка...................................................................... 59 4.5 Микроскопический анализ измельченной «Золотарника кавказского травы» ................................................................................................................................. 64 4.6 Микроскопический анализ порошка «Золотарника кавказского травы» ...... 66 4.7 Морфологическая характеристика корневищ с корнями золотарника кавказского ............................................................................................................. 68 4.8 Анатомическое строение корневищ с корнями золотарника кавказского .... 69 Выводы по главе..................................................................................................... 73 ГЛАВА 5 ФИТОХИМИЧЕСКОЕ ИЗУЧЕНИЕ ТРАВЫ И КОРНЕВИЩ С КОРНЯМИ ЗОЛОТАРНИКА КАВКАЗСКОГО. РАЗРАБОТКА НОРМ КАЧЕСТВА ЗОЛОТАРНИКА КАВКАЗСКОГО ТРАВЫ ................................... 74 4 5.1 Анализ травы и корневищ с корнями золотарника кавказского с помощью качественных реакций .......................................................................... 74 5.2 Изучение фенольных соединений травы золотарника кавказского методом БХ ............................................................................................................................ 75 5.3 Обнаружение рутина методом ТСХ в «Золотарника кавказского траве» ..... 78 5.4 Изучение фенольных соединений золотарника кавказского травы методом ВЭЖХ ...................................................................................................... 79 5.5 Количественное определение флавоноидов в пересчете на рутин в «Золотарника кавказского траве» методом дифференциальной спектрофотометрии ................................................................................................ 82 5.6 Количественное определение фенолкарбоновых кислот в траве и корневищах с корнями золотарника кавказского методом спектрофотомерии в пересчете на кофейную кислоту ........................................ 89 5.7 Количественное определение дубильных веществ в траве и корневищах с корнями золотарника кавказского ......................................................................... 93 5.8 Изучение тритерпеновых гликозидов травы золотарника кавказского ........ 95 5.9 Изучение полиацетиленовых соединений корневищ с корнями золотарника кавказского ........................................................................................ 99 5.10 Количественное определение органических кислот в траве золотарника кавказского ...................................................................................... 100 5.11 Изучение органических кислот травы золотарника кавказского методом ВЭЖХ ................................................................................................................... 101 5.12 Изучение углеводов травы золотарника кавказского ................................. 103 5.13 Биологически активные соединения травы золотарника кавказского, идентифицированные методом ГЖХ–МС .......................................................... 109 5.14 Изучение аминокислотного состава травы золотарника кавказского ....... 112 5.15 Изучение минерального состава травы золотарника кавказского ............. 113 5.16 Определение некоторых числовых показателей травы и корневищ с корнями золотарника кавказского ....................................................................... 115 5.17 Микробиологическая чистота «Золотарника кавказского травы» ............ 117 5 5.18 Установление срока годности «Золотарника кавказского травы» ............ 118 Выводы по главе................................................................................................... 120 ГЛАВА 6 ПРЕДВАРИТЕЛЬНЫЕ ТЕХНОЛОГИЧЕСКИЕ ИССЛЕДОВАНИЯ ПО РАЗРАБОТКЕ «ЗОЛОТАРНИКА КАВКАЗСКОГО ТРАВЫ ЭКСТРАКТА СУХОГО», СТАНДАРТИЗАЦИЯ ПОЛУЧЕННОГО ЭКСТРАКТА И ПРЕДВАРИТЕЛЬНОЕ ИЗУЧЕНИЕ ЕГО ФАРМАКОЛОГИЧЕСКОЙ АКТИВНОСТИ .................................................................................................... 121 6.1 Получение «Золотарника кавказского травы экстракта сухого» ................. 121 6.2 Разработка методик стандартизации «Золотарника кавказского травы экстракта сухого» ................................................................................................. 122 6.2.1 Общие показатели ....................................................................................... 122 6.2.2 Изучение фенольных соединений ............................................................... 124 6.2.3 Количественное определение
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