RU2639091C2 - Production method of medicinal plants nanocapsules with cardiotonic action - Google Patents
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- 239000002088 nanocapsule Substances 0.000 title claims abstract description 17
- 230000003177 cardiotonic effect Effects 0.000 title claims description 5
- 238000004519 manufacturing process Methods 0.000 title abstract description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000000725 suspension Substances 0.000 claims abstract description 8
- 235000009917 Crataegus X brevipes Nutrition 0.000 claims abstract description 7
- 235000013204 Crataegus X haemacarpa Nutrition 0.000 claims abstract description 7
- 235000009685 Crataegus X maligna Nutrition 0.000 claims abstract description 7
- 235000009444 Crataegus X rubrocarnea Nutrition 0.000 claims abstract description 7
- 235000009486 Crataegus bullatus Nutrition 0.000 claims abstract description 7
- 235000017181 Crataegus chrysocarpa Nutrition 0.000 claims abstract description 7
- 235000009682 Crataegus limnophila Nutrition 0.000 claims abstract description 7
- 235000004423 Crataegus monogyna Nutrition 0.000 claims abstract description 7
- 235000002313 Crataegus paludosa Nutrition 0.000 claims abstract description 7
- 235000009840 Crataegus x incaedua Nutrition 0.000 claims abstract description 7
- 229940098465 tincture Drugs 0.000 claims abstract description 7
- 229920002148 Gellan gum Polymers 0.000 claims abstract description 6
- 239000000216 gellan gum Substances 0.000 claims abstract description 6
- 235000010492 gellan gum Nutrition 0.000 claims abstract description 6
- 239000001793 Citric acid esters of mono and diglycerides of fatty acids Substances 0.000 claims abstract description 4
- 238000003756 stirring Methods 0.000 claims abstract description 4
- 240000000171 Crataegus monogyna Species 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims description 17
- 238000002360 preparation method Methods 0.000 claims description 6
- 241000196324 Embryophyta Species 0.000 claims description 4
- 235000013305 food Nutrition 0.000 abstract description 3
- 239000004094 surface-active agent Substances 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 230000001133 acceleration Effects 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000003094 microcapsule Substances 0.000 description 6
- 241001092040 Crataegus Species 0.000 description 5
- 239000007921 spray Substances 0.000 description 4
- 238000005259 measurement Methods 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 239000004135 Bone phosphate Substances 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102220547770 Inducible T-cell costimulator_A23L_mutation Human genes 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- -1 glycerol ester Chemical class 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000002728 pyrethroid Substances 0.000 description 1
- 239000004065 semiconductor Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001132 ultrasonic dispersion Methods 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
- A61J3/07—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of capsules or similar small containers for oral use
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
- A61K36/734—Crataegus (hawthorn)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82B—NANOSTRUCTURES FORMED BY MANIPULATION OF INDIVIDUAL ATOMS, MOLECULES, OR LIMITED COLLECTIONS OF ATOMS OR MOLECULES AS DISCRETE UNITS; MANUFACTURE OR TREATMENT THEREOF
- B82B3/00—Manufacture or treatment of nanostructures by manipulation of individual atoms or molecules, or limited collections of atoms or molecules as discrete units
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- Steroid Compounds (AREA)
- Manufacturing Of Micro-Capsules (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
Изобретение относится к области нанотехнологии, медицины и пищевой промышленности.The invention relates to the field of nanotechnology, medicine and the food industry.
Ранее были известны способы получения микрокапсул.Previously known methods for producing microcapsules.
В пат. 2173140, МПК А61К 009/50, А61К 009/127, Российская Федерация, опубликован 10.09.2001, предложен способ получения кремнийорганолипидных микрокапсул с использованием роторно-кавитационной установки, обладающей высокими сдвиговыми усилиями и мощными гидроакустическими явлениями звукового и ультразвукового диапазона для диспергирования.In US Pat. 2173140, IPC A61K 009/50, A61K 009/127, Russian Federation, published September 10, 2001, a method for producing silicon organolipid microcapsules using a rotary-cavitation unit with high shear forces and powerful sonar acoustic and ultrasonic dispersion ranges is proposed.
Недостатком данного способа является применение специального оборудования - роторно-кавитационной установки, которая обладает ультразвуковым действием, что оказывает влияние на образование микрокапсул и при этом может вызывать побочные реакции в связи с тем, что ультразвук разрушающе действует на полимеры белковой природы, поэтому предложенный способ применим при работе с полимерами синтетического происхожденияThe disadvantage of this method is the use of special equipment - a rotary cavitation unit, which has an ultrasonic effect, which affects the formation of microcapsules and can cause adverse reactions due to the fact that ultrasound destructively affects polymers of a protein nature, therefore, the proposed method is applicable when work with polymers of synthetic origin
В пат. 2359662, МПК А61К 009/56, A61J 003/07, B01J 013/02, A23L 001/00, опубликован 27.06.2009, Российская Федерация, предложен способ получения микрокапсул хлорида натрия с использованием распылительного охлаждения в распылительной градирне Niro при следующих условиях: температура воздуха на входе 10°С, температура воздуха на выходе 28°С, скорость вращения распыляющего барабана 10000 оборотов/мин. Микрокапсулы по изобретению обладают улучшенной стабильностью и обеспечивают регулируемое и/или пролонгированное высвобождение активного ингредиента.In US Pat. 2359662, IPC A61K 009/56, A61J 003/07, B01J 013/02, A23L 001/00, published June 27, 2009, Russian Federation, a method for producing sodium chloride microcapsules using spray cooling in a Niro spray cooling tower under the following conditions: temperature air inlet 10 ° C, air outlet temperature 28 ° C, the rotation speed of the spray drum 10,000 rpm. The microcapsules of the invention have improved stability and provide controlled and / or prolonged release of the active ingredient.
Недостатками предложенного способа являются длительность процесса и применение специального оборудования, комплекс определенных условий (температура воздуха на входе 10°С, температура воздуха на выходе 28°С, скорость вращения распыляющего барабана 10000 оборотов/мин).The disadvantages of the proposed method are the duration of the process and the use of special equipment, a set of certain conditions (air temperature at the inlet 10 ° C, air temperature at the outlet 28 ° C, rotation speed of the spray drum 10,000 rpm).
Наиболее близким методом является способ, предложенный в пат. 2134967, МПК A01N 53/00, A01N 25/28, опубликован 27.08.1999, Российская Федерация (1999). В воде диспергируют раствор смеси природных липидов и пиретроидного инсектицида в весовом отношении 2-4: 1 в органическом растворителе, что приводит к упрощению способа микрокапсулирования.The closest method is the method proposed in US Pat. 2134967, IPC A01N 53/00, A01N 25/28, published on 08.27.1999, Russian Federation (1999). A solution of a mixture of natural lipids and a pyrethroid insecticide in a weight ratio of 2-4: 1 in an organic solvent is dispersed in water, which simplifies the microencapsulation method.
Недостатком метода является диспергирование в водной среде, что делает предложенный способ неприменимым для получения микрокапсул водорастворимых препаратов в водорастворимых полимерах.The disadvantage of this method is dispersion in an aqueous medium, which makes the proposed method inapplicable for producing microcapsules of water-soluble preparations in water-soluble polymers.
Техническая задача - упрощение и ускорение процесса получения нанокапсул, уменьшение потерь при получении нанокапсул (увеличение выхода по массе).The technical task is to simplify and accelerate the process of obtaining nanocapsules, reduce losses in obtaining nanocapsules (increase in yield by mass).
Решение технической задачи достигается способом получения нанокапсул лекарственных растений, обладающих кардиотоническим действием, отличающимся тем, что в качестве оболочки нанокапсул используется геллановая камедь, а в качестве ядра - настойка боярышника, при получении нанокапсул методом осаждения нерастворителем с применением хлороформа в качестве осадителя.The solution of the technical problem is achieved by the method of producing nanocapsules of medicinal plants having a cardiotonic effect, characterized in that gellan gum is used as the shell of the nanocapsules, and tincture of hawthorn is used as the core, when nanocapsules are prepared by the non-solvent precipitation method using chloroform as a precipitant.
Отличительной особенностью предлагаемого метода является получение нанокапсул при использовании геллановой камеди в качестве оболочки частиц и настоек лекарственных растений, обладающих кардиотоническим действием, - в качестве ядра.A distinctive feature of the proposed method is the preparation of nanocapsules using gellan gum as a shell of particles and tinctures of medicinal plants with a cardiotonic effect, as a core.
Результатом предлагаемого метода являются получение нанокапсул лекарственных растений, обладающих кардиотоническим действием.The result of the proposed method is the preparation of nanocapsules of medicinal plants with a cardiotonic effect.
ПРИМЕР 1. Получение нанокапсул настойки боярышника, соотношение ядро : оболочка 1:3EXAMPLE 1. Obtaining nanocapsules of tincture of hawthorn, the ratio of core: shell 1: 3
10 мл настойки боярышника добавляют в суспензию 3 г геллановой камеди в гексане в присутствии 0,01 г препарата Е472с (сложный эфир глицерина с одной-двумя молекулами пищевых жирных кислот и одной-двумя молекулами лимонной кислоты, причем лимонная кислота, как трехосновная, может быть этерифицирована другими глицеридами и как оксокислота - другими жирными кислотами. Свободные кислотные группы могут быть нейтрализованы натрием) в качестве поверхностно-активного вещества при перемешивании 1000 об/мин. Полученную суспензию отфильтровывают и сушат при комнатной температуре.10 ml of hawthorn tincture is added to a suspension of 3 g of gellan gum in hexane in the presence of 0.01 g of the preparation E472c (glycerol ester with one or two molecules of food fatty acids and one or two molecules of citric acid, and citric acid, as a tribasic, can be etherified with other glycerides and as an acid with other fatty acids. Free acid groups can be neutralized with sodium) as a surfactant with stirring at 1000 rpm. The resulting suspension is filtered and dried at room temperature.
Получено 4 г порошка нанокапсул. Выход составил 100%.Received 4 g of nanocapsule powder. The yield was 100%.
ПРИМЕР 2. Получение нанокапсул настойки боярышника, соотношение ядро : оболочка 1:1EXAMPLE 2. Obtaining nanocapsules of tincture of hawthorn, the ratio of the core: shell 1: 1
10 мл настойки боярышника добавляют в суспензию 1 г геллановой камеди в гексане в присутствии 0,01 г препарата Е472с в качестве поверхностно-активного вещества при перемешивании 1000 об/мин. Полученную суспензию отфильтровывают и сушат при комнатной температуре.10 ml of hawthorn tincture is added to a suspension of 1 g of gellan gum in hexane in the presence of 0.01 g of the preparation E472c as a surfactant with stirring at 1000 rpm. The resulting suspension is filtered and dried at room temperature.
Получено 2 г порошка нанокапсул. Выход составил 100%.Received 2 g of nanocapsule powder. The yield was 100%.
ПРИМЕР 3. Определение размеров нанокапсул методом NTAEXAMPLE 3. Determination of the size of nanocapsules by NTA
Измерения проводили на мультипараметрическом анализаторе наночастиц Nanosight LM0 производства Nanosight Ltd (Великобритания) в конфигурации HS-BF (высокочувствительная видеокамера Andor Luca, полупроводниковый лазер с длиной волны 405 нм и мощностью 45 мВт). Прибор основан на методе анализа траекторий наночастиц (Nanoparticle Tracking Analysis, NTA), описанном в ASTM E2834.The measurements were carried out on a Nanosight LM0 multiparameter nanoparticle analyzer manufactured by Nanosight Ltd (Great Britain) in the HS-BF configuration (Andor Luca high-sensitivity video camera, 405 nm semiconductor laser with a power of 45 mW). The device is based on the Nanoparticle Tracking Analysis (NTA) method described in ASTM E2834.
Оптимальным разведением для разведения было выбрано 1:100. Для измерения были выбраны параметры прибора: Camera Level=16, Detection Threshold=10 (multi), Min Track Length:Auto, Min Expected Size: Auto. длительность единичного измерения 215s, использование шприцевого насоса.The optimal dilution for dilution was 1: 100. For the measurement, the device parameters were selected: Camera Level = 16, Detection Threshold = 10 (multi), Min Track Length: Auto, Min Expected Size: Auto. duration of a single measurement of 215s, the use of a syringe pump.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2680808C1 (en) * | 2018-04-06 | 2019-02-27 | Александр Александрович Кролевец | Method of obtaining dandelion dry extract nanocapsules |
| RU2680805C1 (en) * | 2018-04-02 | 2019-02-27 | Александр Александрович Кролевец | Method for preparing nanocapsules of devil's-club dry extract in guar gum |
| RU2681837C1 (en) * | 2018-04-19 | 2019-03-13 | Александр Александрович Кролевец | Method of producing dry extract of nanocapsules of propolis |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2134967C1 (en) * | 1997-05-30 | 1999-08-27 | Шестаков Константин Алексеевич | Method of preparing microcapsulated preparations containing pyrethroid insecticides |
| WO2004064544A1 (en) * | 2003-01-22 | 2004-08-05 | Durafizz, Llc | Microencapsulation for sustained delivery of carbon dioxide |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2134967C1 (en) * | 1997-05-30 | 1999-08-27 | Шестаков Константин Алексеевич | Method of preparing microcapsulated preparations containing pyrethroid insecticides |
| WO2004064544A1 (en) * | 2003-01-22 | 2004-08-05 | Durafizz, Llc | Microencapsulation for sustained delivery of carbon dioxide |
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| Title |
|---|
| NAGAVARMA B. V. N. Different techniques for preparation of polymeric nanoparticles, Asian Journal Pharm Clin Res, vol.5, suppl 3, 2012, стр.16-23. * |
| PARRIS N. et.al. Encapsulation of essential oils in zein nanospherical particles / J. Agric. Food Chem., 2005. 53: p. 4788-4792. * |
| PARRIS N. et.al. Encapsulation of essential oils in zein nanospherical particles / J. Agric. Food Chem., 2005. 53: p. 4788-4792. ЧУЕШОВ В.И. Промышленная технология лекарств в 2-х томах, том 2, 2002, стр. 383. * |
| ЧУЕШОВ В.И. Промышленная технология лекарств в 2-х томах, том 2, 2002, стр. 383. * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2680805C1 (en) * | 2018-04-02 | 2019-02-27 | Александр Александрович Кролевец | Method for preparing nanocapsules of devil's-club dry extract in guar gum |
| RU2680808C1 (en) * | 2018-04-06 | 2019-02-27 | Александр Александрович Кролевец | Method of obtaining dandelion dry extract nanocapsules |
| RU2681837C1 (en) * | 2018-04-19 | 2019-03-13 | Александр Александрович Кролевец | Method of producing dry extract of nanocapsules of propolis |
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