SU806037A1 - Antianginal agent - Google Patents

Antianginal agent Download PDF

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Publication number
SU806037A1
SU806037A1 SU782605039A SU2605039A SU806037A1 SU 806037 A1 SU806037 A1 SU 806037A1 SU 782605039 A SU782605039 A SU 782605039A SU 2605039 A SU2605039 A SU 2605039A SU 806037 A1 SU806037 A1 SU 806037A1
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SU
USSR - Soviet Union
Prior art keywords
effect
antianginal
nitroglycerin
water
acrylamide
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SU782605039A
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Russian (ru)
Inventor
Эдуард Арменакович Бабаян
Галина Анатольевна Герасимова
Анатолий Борисович Давыдов
Рустам Исмаилович Утямышев
Геннадий Львович Хромов
Владимир Исаакович Метелица
Анатолий Михайлович Вихерт
Original Assignee
Всесоюзный Кардиологический Научныйцентр Amh Cccp
Всесоюзный Научно-Исследовательскийи Испытательный Институт Медицинскойтехники
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Application filed by Всесоюзный Кардиологический Научныйцентр Amh Cccp, Всесоюзный Научно-Исследовательскийи Испытательный Институт Медицинскойтехники filed Critical Всесоюзный Кардиологический Научныйцентр Amh Cccp
Priority to SU782605039A priority Critical patent/SU806037A1/en
Priority to CA324,996A priority patent/CA1127082A/en
Priority to DE19792913752 priority patent/DE2913752A1/en
Priority to GB7912104A priority patent/GB2021610B/en
Priority to JP54041172A priority patent/JPS6024763B2/en
Priority to GB8120761A priority patent/GB2078771B/en
Priority to FR7908827A priority patent/FR2421610A1/en
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Publication of SU806037A1 publication Critical patent/SU806037A1/en

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/70Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7038Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7053Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/21Esters, e.g. nitroglycerine, selenocyanates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0053Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/70Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7007Drug-containing films, membranes or sheets
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/70Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7038Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7053Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
    • A61K9/7061Polyacrylates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/04Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure

Abstract

A resolvable carrier may be combined with an active ingredient to produce an antianginal composition, preferably in the form of a film or plate of thickness 0.1 to 1.5 mm. The carrier is biologically soluble and resolvable, and is a homopolymer of acrylamide or of vinylpyrrolidone or is a copolymer of these. Alternatively, it can be a copolymer of these two and an acrylate. It preferably has a molecular weight of from 50,000 to 1,000,000. The amount of active ingredient is preferably from 3 to 30% by weight. A preferred active ingredient is glycerol trinitrate.

Description

(54) АНТИАНГИНАЛЬНОЕ СРЕДСТВО(54) ANTIANGINAL MEANS

Изобретение относитс  к медицине, а именно фармации, к лекарственным средствам, используемым в кардиологии дл  лечени  коронарной недостаточности. В медицинской практике известно применение в качестве антиангинального средства нитроглицерина дл  лечени  приступов стенокардни Ц. Однако известное антиангинальное средство обладает побочным эффектом и кратковременным действием. Цель изобретени  - снижение побочного дей стви  и пролонгирование действи  антиангиналь ного средства. Поставленна  цель достигаетс  тем, что в со став антиангинального средства дл  снижени  побочного действи  в качестве водорастворимого носител  введены гомополимеры акриламида N-винилпирролидона или их сополимеры с акрклатами при следующем количественном соотношении компонентов, вес. %: Антиангинальное средство на основе преимущественно ннтро глицерина3-30 Водорастворимый носитель70-97 А с целью пролонгировани  действи  оно дополнительно содержит дисперсии твердых жиров с температурой плавлени  30-50° С от 3 до 30 вес. % сверх 100%. Антиангннальные средства получают, использу  известные технологические операции - лекарственный препгфат и водорастворимый носитель раствор ют в растворител х, совмещающихс  друг с дфугом или в общем растворителе , смешивают растворы, обеспечива  необходимое соошошение компонентов, отливают luioiKH толццгаой 0,1-1,0 мм на инертных подложках , сушат пленки при температуре до 40°С до остаточного содержани  растворител  не более 10%, после чего формуют пластинки заданного размера, обеспечива  разовую дозу препарата. Дл  обеспечени  пролонгированного действи  перед отливом пленок в смесь растворов препаратов и водорастворимого носител  ввод т дисперсию жира в том же растворителе , обеспечива  требуемое его содержание в составе антиангинального средства. Пример. Приготавливают композицию лекарственного средства следующего состава , %: Нитроглицерин3 Полиакриламид (молекул рна  масса 700000) Компоненты последовательно раствор ют в дистиллированной воде, ползша  растворы 10-20%-ной концентра щи. Из растворов отли вают пленки любым известным способом (по вом на инертную подложку, напылением, осаж дением в электростатическом поле и т.д.) из которых вырубают пластинки желаемой форм и размеров, обеспечива  необходимую дозиро ку лекарственного препарата. Пример. Приготавливают композицию лекарственного средства следующего сост ва, %: Нитроглицерин 30 Сополимер акриламида, N-винилпирролидона и зтилакрилата (соотнощение 1:1:1; молекул рна  масса 80 000) 70 Компоненты последовательно раствор ют в водно-спиртовой смеси при соотнощении во да:спирт 75:25, получа  растворы 10-20%-ной концентрации. Далее, как описано в примере П р и м е р 3. Приготавливают композицию лекарственного средства следующего состава , %: Нитроглицерин10 Сополимер акриламида, N-винилпирролидона и бутилакрилата (соотнощение 1:0,5:0,3; молекул рна  масса 80 000)90 Компоненты последовательно раствор ют в водно-спиртовой смеси при соотнощении вода спирт 75:25, получа  растворы 10-20%-ной концентрации. Далее, как описано в примере П р и м е р 4. Приготавливают композиц лeк ctвeннoгo средства следующего состава, Нитроглицерин3 Сополимер акриламида, N-вшшлпирролидона и этилакрилата (соотнощение 0,6:0,2:0,2; молекул рна  масса 50 000)97 Масло какао3 ( сверх 100) Компоненты последовательно раствор ют и диспергируют в водно-спиртовом растворе пр соотношенни вода:сшфт 75:25, получа  раств {ш дисперсии 10-20%-ной концентрации . Дл  диспергировани  могут использоватьс  любые известные способы (механическое перемещив , ультразвукова  обработка и др.). Далее, описано в примере 1. П р и м е р 5. Приготавливают композилекарственного средства следующего сова , %: Нитроглицерин5 Сополимер акриламида, N- винилпирролидона и этилакрилата (соотнощение 0,6:0,2:0,2; молекул рна  масса 500 000)95 Масло какао 30 ( сверх 100) Далее, как описано в примере 4. Пример 6. Приготавливают композилекарственного средства следующего соа , %: Нитроглицерин5 Сополимер акриламида, N-винилпирролидона и этилакрилата (соотнощение 0,6:0,2:0,2; молекул рна  масса 500 000)95 Гидрогенизировашюе хлопковое масло .10 ( сверх 100) Далее, как описано в примере 4. П р И М е р 7. Приготавливают композилекарственного средства следующего соста%: Пентаэритриттетранитрат20 Сополимер акриламида, М-винилпирролидона и зтилакрилата (соотнощение 0,6:0,2:0,2; молекул рна 80 масса 500 000)ю Масло какао(сверх 100) Далее, как описано в примере 4. ПримерЗ. Приготавливают композилекарственного средства следующего сова , %: Нитроглицерин5 Сополимер акриламида, N-виншпгарролидона и этилакрилата (соотнощение 0,6:0,2:0,2; молекул рна  масса 500 000)95 Гищюгениз1фоваш1ый ланолин10 ( сверх 100) Далее, как описано в примере 4. П р н м е р 9. Приготавливают композилекарственного средства следующего сова , %: Изосорбитдишлграт20 ( шгтросорбит) Сополимер акриламида, N-винилпирролидона и этилакрилата (соотнощение 0,6:0,2:0,2; молекул рна  масса 500 000) Компоненты последовательно раствор ют в водно-спиртовой смеси при соотношении вода спирт 50:50, получа  растворы 15-20%-ной концентрации. Далее, как описано в примере 1. В отличие от известных полимерные носители указанной природы при контакте с водными растворами обеспечивают более равноме ное выделение лекарственного препарата, что снижает и устран ет побочные эффекты в виде головных болей или резкого изменени  кр в ного давлени , наблюдаемые при приеме, известных антиангинальных средств.The invention relates to medicine, namely pharmacy, to drugs used in cardiology for the treatment of coronary insufficiency. In medical practice, it is known to use nitroglycerin as an antianginal agent for treating strokes of angina C. However, the known antianginal agent has a side effect and a short-term effect. The purpose of the invention is to reduce the side effects and prolong the action of the antianginal agent. The goal is achieved by the fact that homopolymers of acrylamide N-vinylpyrrolidone or their copolymers with acrylates are introduced into the composition of an antianginal agent to reduce the side effects as a water-soluble carrier with the following quantitative ratio of the components, wt. %: Antianginal agent based on predominantly ntro glycerol3-30 Water-soluble carrier 70-97 A for the purpose of prolonging its action, it additionally contains dispersions of solid fats with a melting point of 30-50 ° C from 3 to 30 wt. % over 100%. Anti-angnostic agents are obtained using known technological procedures — the medicinal prepgfat and the water-soluble carrier are dissolved in solvents that are combined with each other or in a common solvent; the solutions are mixed, providing the necessary alignment of the components, cast with 0.1-1.0 mm thick on inert luioiKH the substrates, the films are dried at a temperature up to 40 ° C to a residual solvent content of not more than 10%, after which plates of a given size are formed, providing a single dose of the preparation. To ensure prolonged action, before the films are cast, a dispersion of fat in the same solvent is introduced into the mixture of the solutions of the preparations and the water-soluble carrier, ensuring the required content of the antianginal agent. Example. A drug composition of the following composition is prepared,%: Nitroglycerin3 Polyacrylamide (molecular weight 700,000) The components are successively dissolved in distilled water, crawling solutions of 10–20% concentration of shchi. Films are poured from solutions by any known method (on an inert substrate, sputtering, deposition in an electrostatic field, etc.) from which plates of the desired shape and size are cut down, providing the necessary dosage of the drug. Example. A drug composition of the following composition is prepared,%: Nitroglycerin 30 Acrylamide, N-vinylpyrrolidone and ethyl acrylate copolymer (ratio 1: 1: 1; molecular weight 80,000) 70 The components are successively dissolved in an aqueous-alcohol mixture at a ratio of: alcohol 75:25, obtaining solutions of 10–20% concentration. Further, as described in example EXAMPLE 3. A composition of a medicinal product of the following composition is prepared,%: Nitroglycerin10 Acrylamide, N-vinylpyrrolidone and butyl acrylate copolymer (ratio 1: 0.5: 0.3; molecular weight 80,000) 90 The components are sequentially dissolved in a water-alcohol mixture at a ratio of water to alcohol 75:25, yielding solutions of 10–20% concentration. Further, as described in Example EXAMPLE 4. Prepare a Composition of Lacquers of Equivalent Agents of the Following Composition, Nitroglycerin 3 Acrylamide, N-Svirpyrrolidone and ethyl acrylate copolymer (0.6: 0.2: 0.2; molecular weight 50,000 ) 97 Cocoa butter 3 (over 100) The components are sequentially dissolved and dispersed in a water-alcohol solution at a ratio of water: cotton 75:25, obtaining a solution {w dispersion of 10–20% concentration. For dispersion, any known methods can be used (mechanical displacement, ultrasonic treatment, etc.). Further, it is described in Example 1. EXAMPLE 5. Composite drugs are prepared following owl,%: Nitroglycerin 5 Acrylamide, N-vinylpyrrolidone and ethyl acrylate copolymer (ratio 0.6: 0.2: 0.2; molecular weight 500 000) 95 Cocoa Butter 30 (in excess of 100) Further, as described in Example 4. Example 6. Prepare a composite drug of the following coa,%: Nitroglycerin 5 Acrylamide, N-vinylpyrrolidone and ethyl acrylate copolymer (ratio of 0.6: 0.2: 0, 2; molecular weight 500,000) 95 Hydrogenated cottonseed oil .10 (over 100) Further, as described in approx. 4. Compositing drugs of the following composition are prepared: Pentaerythritol tetranitrate20 Acrylamide copolymer, M-vinylpyrrolidone and ethyl acrylate (ratio 0.6: 0.2: 0.2; molecular weight 80,000,000) o Oil cocoa (over 100) Further, as described in example 4. Example3. Composite the following owl is prepared,%: Nitroglycerin5 Acrylamide, N-vinsphgarrolidone and ethyl acrylate copolymer (ratio 0.6: 0.2: 0.2; molecular weight 500,000) 95 Gysthygenizene lanolin 10 (over 100) Next, as described in example 4. Example 9. Composites are prepared with the following owl,%: Isosorbittistilgrat20 (schtrosorbit) Acrylamide, N-vinylpyrrolidone and ethyl acrylate copolymer (ratio 0.6: 0.2: 0.2; molecular weight 500,000) The components are sequentially dissolved in a water-alcohol mixture at a ratio of Water alcohol 50:50, obtaining solutions of 15-20% concentration. Further, as described in Example 1. In contrast to the known polymeric carriers of the indicated nature, upon contact with aqueous solutions, they provide a more even release of the drug, which reduces and eliminates side effects in the form of headaches or drastic changes in the crush pressure. admission, known antianginal drugs.

Гранулы с сахаром 40 70 100Granules with sugar 40 70 100

Пленки на основе Based films

20 35 полиакрил амида20 35 polyacryl amide

Claims (2)

1. Антиангинальное средство на основе преимущественно нитроглицерина, о т л и ч аю щ ее с   тем, что, с целью снижени  побочного действи , оно содержит в качестве водорастворимого носител  гомополимеры акриламида , N-винилпирролидона или их сополимеры с акрилатами при следующем количественном соотношении компонентов, вес. %:1. Anti-anginal agent based mainly on nitroglycerin, which means that, in order to reduce the adverse effect, it contains as a water-soluble carrier homopolymers of acrylamide, N-vinylpyrrolidone or their copolymers with acrylates with the following quantitative ratio of the components , weight. %: Антиангинальное средствоAntianginal agent на основе преимущественноbased mainly 100100 8080 6060 нитроглицерина3-30nitroglycerin 3-30 Водорастворимый носитель70-97Water soluble carrier 70-97 2. Средство по п. 1, о т л н ч а ю щ е- . е с-  тем, что, с целью щУолонгировани  действи , оно дополнительно содержит дисперсии твердых жиров с температурой плавлени  30-50 С от 3 до 30 вес.% сверх 100%.2. Means under item 1, about t of l nch and ya sh-. So that, in order to have a long-lasting effect, it additionally contains dispersions of solid fats with a melting point of 30-50 ° C from 3 to 30% by weight in excess of 100%. Источники информации, прин тые во виимание при экспертизе 1. Мащковский М. Д. Лекарственные средства . М., 1977, т. I, с. 373. 76 В таблице показана кинетика выделени  нитроглицерина из различных антиангинальных средств дл  сублингвального применени . Введенне в состав антиангинального средства дисперсии твердого Ж1фа, 1гапример масла какао , приводит к cyutecTBeinfflKry пролонгированию положительното гемодинамиче(гкого эффекта , составл ющего в среднем 3 ч, в то врем  как при использовании обычных средств длительность аналогичного действи  составл ет 20-30 мин. Использование аитиангинальных средств, обладающих побочным эффектом и пролонгированным действием, обеспечивает высокий лечебный .эффект при одновременном 3-5-кратном снижении расхода лекарственных препаратов.Sources of information taken during examination 1. Mashchkovsky M. D. Medicinal products. M., 1977, Vol. I, p. 373. 76 The table shows the kinetics of excretion of nitroglycerin from various antianginal drugs for sublingual use. Introduced to the antianginal solid dispersion agent, such as cocoa butter, results in cyutecTBeinfflKry prolonging positively hemodynamic (a mild effect averaging 3 hours, while using conventional means, the duration of a similar effect is 20-30 minutes. agents with a side effect and a prolonged action, provides a high therapeutic effect with a simultaneous 3-5-fold reduction in the consumption of drugs.
SU782605039A 1978-04-06 1978-04-06 Antianginal agent SU806037A1 (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
SU782605039A SU806037A1 (en) 1978-04-06 1978-04-06 Antianginal agent
CA324,996A CA1127082A (en) 1978-04-06 1979-04-05 Antianginal film and method of treating ischemic heart disease
DE19792913752 DE2913752A1 (en) 1978-04-06 1979-04-05 MEDICINAL FILM WITH ANTIANGINAL EFFECT
GB7912104A GB2021610B (en) 1978-04-06 1979-04-06 Antianginal composition
JP54041172A JPS6024763B2 (en) 1978-04-06 1979-04-06 anti-angina film
GB8120761A GB2078771B (en) 1978-04-06 1979-04-06 Drug carrier
FR7908827A FR2421610A1 (en) 1978-04-06 1979-04-06 MEDICINAL FILM BASED ON AN ACTIVE SUBSTANCE WITH ANTI ANGINOUS ACTION SUCH AS NITROGLYCERIN OR ISOSORBIDE DIMITRATE

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
SU782605039A SU806037A1 (en) 1978-04-06 1978-04-06 Antianginal agent

Publications (1)

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SU806037A1 true SU806037A1 (en) 1981-02-23

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SU782605039A SU806037A1 (en) 1978-04-06 1978-04-06 Antianginal agent

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JP (1) JPS6024763B2 (en)
CA (1) CA1127082A (en)
DE (1) DE2913752A1 (en)
FR (1) FR2421610A1 (en)
GB (2) GB2021610B (en)
SU (1) SU806037A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4529589A (en) * 1981-07-14 1985-07-16 Davydov Anatoly B Pharmaceutical composition for the treatment of diabetes mellitus

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4291015A (en) * 1979-08-14 1981-09-22 Key Pharmaceuticals, Inc. Polymeric diffusion matrix containing a vasodilator
IL61721A (en) * 1980-12-16 1984-03-30 Blank Izhak Nitroglycerin preparations
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Also Published As

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FR2421610B1 (en) 1982-11-12
JPS6024763B2 (en) 1985-06-14
JPS54154511A (en) 1979-12-05
GB2021610B (en) 1982-10-20
FR2421610A1 (en) 1979-11-02
GB2078771A (en) 1982-01-13
GB2021610A (en) 1979-12-05
GB2078771B (en) 1983-03-09
DE2913752A1 (en) 1979-12-20
CA1127082A (en) 1982-07-06

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