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WO2008036003A1 - Composition pharmaceutique à inhaler - Google Patents

Composition pharmaceutique à inhaler Download PDF

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Publication number
WO2008036003A1
WO2008036003A1 PCT/RU2007/000506 RU2007000506W WO2008036003A1 WO 2008036003 A1 WO2008036003 A1 WO 2008036003A1 RU 2007000506 W RU2007000506 W RU 2007000506W WO 2008036003 A1 WO2008036003 A1 WO 2008036003A1
Authority
WO
WIPO (PCT)
Prior art keywords
biologically active
particles
inhalation
active substance
respirable
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/RU2007/000506
Other languages
English (en)
Russian (ru)
Inventor
Vladimir Evgenievich Nebolsin
Aleksandr Grigorievich Chuchalin
Evgeny Viktorovich Babarskov
Galina Aleksandrovna Zheltukhina
Violetta Leonidovna Kovaleva
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Priority to EA200900464A priority Critical patent/EA016363B1/ru
Publication of WO2008036003A1 publication Critical patent/WO2008036003A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics

Definitions

  • the invention relates to pharmaceutical compositions for inhalation, and can also be attributed to powder pharmaceutical compositions for inhalation using finely dispersed biologically active substances on inert carriers without a binder.
  • Biologically active substances used to treat obstructive airways diseases such as, for example, bronchial asthma, chronic bronchitis and the like, must penetrate deeply into the patient's lungs.
  • the particles of biologically active substances have respirable sizes, in other words, their aerodynamic diameters should not exceed 5-7 microns [1].
  • Powders consisting of particles of such small sizes have a large surface energy. This is manifested in their high adhesion to surfaces and the formation of large particle agglomerates as a result of cohesive interactions, which impairs the fluidity of the powder and makes it impossible to accurately dose it.
  • powder pharmaceutical compositions consisting of fine particles of biologically active substances of respirable size and coarse particles of biologically inert carriers, or excipients, usually larger than 30 microns, such as, for example, lactose, glucose, mannitol, xylitol, starch, sodium benzoate.
  • Powdered pharmaceutical compositions are administered to the lungs of patients using powder inhalers.
  • metered-dose powder inhalers for example, TURVUNALER from ASTRA, NOVOLIZER from VIATRIS, EASYHALER from ORION, CLISKNALER from INNOVATA BIOMED.
  • Designs of such powder inhalers include a multi-dose container with a powder pharmaceutical composition, from which, using the built-in dosing mechanism, a single dose of powder, measured by the volume principle in calibrated metering holes, it moves into the air channel. Then, a measured dose of powder is captured by the inspiratory flow of air created by inhalation, disperses and enters the patient's lungs.
  • dispersion does not completely destroy the agglomerates of particles of the pharmaceutical composition, and not more than 20-30% of the amount of biologically active substance contained in a single dose enters the lungs, and most of it, reaching 80%, is deposited in the oropharynx.
  • the respirable fraction - VRF i.e. the mass fraction of particles of the biologically active substance in the aerosol created by inhalation with aerodynamic diameters of less than 5-7 microns.
  • the WFD is determined using cascade impactors or liquid impingers, which make it possible to separate from the aerosol passed through them various fractions of particles in size on separate substrates or in separate volumes of the sorbing liquid [2].
  • the WGF depends on the physico-chemical properties, such as, for example, adhesion and cohesion of a biologically active substance and its content in the composition.
  • Glutaryl histamine is a known biologically active substance belonging to the group of derivative peptides and having a pronounced anti-inflammatory, anti-allergic, anti-asthma and antiviral effect [4], [9]
  • VRF The minimum value of VRF, providing a therapeutically effective delivery of inhaled administered biologically active substances, should be at least 10%.
  • compositions for inhalation containing a mixture of biologically active substances or mixtures of biologically active substances with an average particle size of less than 10 microns with a physiologically compatible carrier or mixture of carriers with an average particle size of 200 - 1000 microns, characterized in that the biologically active substance or mixture of biologically active substances has an average particle size of more than 0.01 ⁇ m, and the specified carrier or mixture of carriers has a roughness coefficient of more than 1.75, as well as a pharmaceutical composition an inhalation medium containing a mixture of a biologically active substance or a mixture of biologically active substances with an average particle size of 1 to 5 ⁇ m with a physiologically compatible carrier or a mixture of carriers with an average particle size of 300 to 600 ⁇ m, characterized in that said carrier or mixture of carriers has a roughness coefficient more than 1.75.
  • These compositions in particular, consist of a biologically active substance or a mixture of biologically active substances and a carrier. This pharmaceutical composition for inhalation is the closest
  • the technical result to which the invention is directed is the creation of such a pharmaceutical composition for inhalation, in which the mass content of fine particles of biologically active substances of respirable size in combination with coarse, non-respirable, particles of an inert carrier, would provide the maximum value of the respirable fraction during inhalation, taking into account the dosage error, the biologically active substance should contain such a component nt, which would have a pronounced anti-inflammatory, anti-allergic, anti-asthma and anti-viral effect.
  • the proposed pharmaceutical composition for inhalation comprising a finely dispersed biologically active substance in the form of particles of respirable size and a coarse biologically inert carrier in the form of particles of non-respirable sizes, characterized in that the biologically active substance includes glutaryl histamine, in the following ratio of ingredients, max. %:
  • a biologically inert carrier is the rest.
  • the mass content of glutaryl histamine is from 1-50%, while glutaryl histamine is crushed to particles of respirable size: 100% of the particles by weight less than 10 microns, 97% - less than 5 microns, mass median aerodynamic particle diameter is 2 , 0 - 2.5 ⁇ m, then the micronized powder of glutaryl histamine is mixed with a coarse powder of a biologically inert carrier, for example: lactose, glucose, mannitol, xylitol, starch, sodium benzoate, with particles of non-respiratory ra Sizes: 100% of particles by weight less than 300 microns, 90% - less than 200 microns and not more than 10% - less than 90 microns, mass median particle diameter is about 150 microns, the obtained pharmaceutical composition for inhalation, with different values of the mass content of glutaryl histamine: 1; 5; 10; twenty; 30 and 50% are placed in a container of a metered-dose
  • the mass content of glutaryl histamine is 1%, while glutaryl histamine is crushed to particles of respirable size, then the micronized powder of glutaryl histamine is mixed with coarse powder of a biologically inert carrier, xylitol, the mass content is 99%, with particles of non-respirable sizes.
  • the resulting pharmaceutical composition for inhalation is placed in a container of a metered-dose powder inhaler.
  • the mass content of glutaryl histamine is 5%, while glutaryl histamine is crushed to particles of respirable size, then micronized powder of glutaryl histamine is mixed with coarse powder of a biologically inert carrier - glucose, with a mass content of 95%, with particles of non-respirable sizes.
  • the resulting pharmaceutical composition for inhalation is placed in a container of a metered-dose powder inhaler.
  • the mass content of glutaryl histamine is 10%, while glutaryl histamine is crushed to particles of respirable size, then the micronized powder of glutaryl histamine is mixed with a coarse powder of a biologically inert carrier, mannitol, with a mass content of 90%, with particles non-respirable sizes.
  • the resulting pharmaceutical composition for inhalation is placed in a container of a metered-dose powder inhaler.
  • the mass content of glutaryl histamine is 50%, while glutaryl histamine is crushed to particles of respirable size, then micronized powder of glutaryl histamine is mixed with a coarse powder of a biologically inert carrier, sodium benzoate, with a mass content of 50%, with particles of non-respirable sizes.
  • the resulting pharmaceutical composition for inhalation is placed in a container of a metered-dose powder inhaler.
  • the mass content of glutaryl histamine is 6%, while glutaryl histamine is crushed to particles of respirable size, then the micronized powder of glutaryl histamine is mixed with a coarse powder of a biologically inert carrier - lactose, with a mass content of 94%, with particles of non-respirable sizes.
  • the resulting pharmaceutical composition for inhalation is placed in a container of a metered-dose powder inhaler.
  • the mass content of glutaryl histamine is 12%, while glutaryl histamine is crushed to particles of respirable size, then the micronized powder of glutaryl histamine is mixed with a coarse powder of a biologically inert carrier - lactose, with a mass content of 88%, with particles of non-respirable sizes.
  • the resulting pharmaceutical composition for inhalation is placed in a container of a metered-dose powder inhaler.
  • the mass content of glutaryl histamine is 19%, while glutaryl histamine is crushed to particles of respirable size, then micronized glutaryl histamine powder is mixed with a coarsely dispersed powder of a biologically inert carrier - lactose, with a mass content of 81%, with particles of non-volatile size.
  • the resulting pharmaceutical composition for inhalation is placed in a container of a metered-dose powder inhaler.
  • the mass content of glutaryl histamine is 32%, while glutaryl histamine is crushed to particles of respirable size, then the micronized powder of glutaryl histamine is mixed with a coarse powder of a biologically inert carrier - lactose, with a mass content of 68%, with particles of non-respirable sizes.
  • the resulting pharmaceutical composition for inhalation is placed in a container of a metered-dose powder inhaler.
  • the air volumetric velocity of glutaryl histamine and relative dosage error - OPD are determined at a volumetric air velocity of 60 l / min as the standard deviation from the average dose.
  • the amount of glutaryl histamine deposited in various stages of the liquid impinger is determined using a high performance liquid chromatograph with a UV detector.
  • VRF as the mass fraction of glutaryl histamine particles with aerodynamic diameters of less than 5 ⁇ m, is determined by the cumulative particle mass distribution curves of the sizes obtained using the cascade liquid impinger.
  • the proposed pharmaceutical composition for inhalation which includes the biologically active substance glutaryl histamine, with its mass content from 1 to 50%, allows therapeutically effective amounts of glutaryl histamine with VRF from 11 to 42% to be administered into the patient’s lungs, with acceptable accuracy, the SPD is not more than 25%, with the use of metered-dose powder inhalers.
  • a pharmaceutical composition for inhalation in which the mass content of fine particles of a biologically active substance of respirable size in combination with coarse, non-respirable, particles of an inert carrier provides the maximum value of the respirable fraction during inhalation, taking into account the dosage error, while the biologically active substance contains such a component which has a pronounced anti-inflammatory, anti-allergic, anti-asthmatic and anti-virus
  • the main action is glutaryl histamine.
  • the proposed pharmaceutical composition for inhalation has a pronounced pharmacological activity. Thus, the desired technical result is achieved.
  • the invention relates to pharmaceutical compositions for inhalation, namely, powder pharmaceutical compositions for inhalation using finely dispersed biologically active substances on inert carriers without a binder.
  • a pharmaceutical composition for inhalation is proposed in which the mass content of fine particles of a biologically active substance of respirable size, combined with coarse, non-respirable, particles of an inert carrier, provide the maximum value of the respirable fraction during inhalation, taking into account the dosage error, while the biologically active substance contains such a component which has a pronounced anti-inflammatory, anti-allergic, anti-asthmatic and anti-virus the main action is glutaryl histamine.

Landscapes

  • Health & Medical Sciences (AREA)
  • Pulmonology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Otolaryngology (AREA)
  • Epidemiology (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention se rapporte à des compositions pharmaceutiques à inhaler et peut concerner également des compositions pharmaceutiques à inhaler utilisant des substances bioactives sur des supports inertes dépourvus de liant. L'invention vise une composition pharmaceutique à inhaler dans laquelle la teneur pondérale des particules finement dispersées de substance bioactive de dimensions respirables, conjointement avec des particules grossièrement dispersées non respirables de support inerte, assure une valeur maximal de la fraction respirable lors de l'inhalation, compte tenu de l'erreur de dosage; cette substance bioactive doit également contenir un composant possédant une action anti-allergique, anti-asthmatique et antivirale prononcée. Selon l'invention, on propose une composition pharmaceutique à inhaler qui contient une substance bioactive sous forme de particules de dimensions respirables conjointement avec des particules grossièrement dispersées non respirables de support inerte, qui se distingue en ce que la substance bioactive comprend la glutarylhistamine avec un rapport suivant de composants, en % en masse : - Substance bioactive 1-50 - Support bioactif - le reste.
PCT/RU2007/000506 2006-09-19 2007-09-19 Composition pharmaceutique à inhaler Ceased WO2008036003A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EA200900464A EA016363B1 (ru) 2006-09-19 2007-09-19 Фармацевтическая композиция для ингаляции

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
RU2006133521/15A RU2338552C2 (ru) 2006-09-19 2006-09-19 Фармацевтическая композиция для ингаляции
RU2006133521 2006-09-19

Publications (1)

Publication Number Publication Date
WO2008036003A1 true WO2008036003A1 (fr) 2008-03-27

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/RU2007/000506 Ceased WO2008036003A1 (fr) 2006-09-19 2007-09-19 Composition pharmaceutique à inhaler

Country Status (3)

Country Link
EA (1) EA016363B1 (fr)
RU (1) RU2338552C2 (fr)
WO (1) WO2008036003A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120129908A1 (en) * 2009-05-21 2012-05-24 Vladimir Evgenievich Nebolsin Agent For The Prophylaxis And Treatment Of Highly Pathogenic Infectious Diseases
CN103382179A (zh) * 2013-06-05 2013-11-06 四川百利药业有限责任公司 英加韦林的多晶型物及其制备方法
WO2014035297A1 (fr) * 2012-08-30 2014-03-06 Общество С Ограниченной Ответственностью "Фарминтерпрайсез" Procédé et agent thérapeutique pour la prévention et le traitement des maladies provoquées par des virus contenant des (+) arn
KR20140107190A (ko) * 2011-10-11 2014-09-04 엘티디 "발렌타-인텔렉트" 글루타릴 히스타민의 기도 질환 치료 용도

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2221552C2 (ru) * 1998-11-13 2004-01-20 Джаго Рисерч Аг Сухой порошок для ингаляции

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2221552C2 (ru) * 1998-11-13 2004-01-20 Джаго Рисерч Аг Сухой порошок для ингаляции

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
KOVALEVA V.L. ET AL.: "Issledovanie effektivnosti potentsialnogo lekarstvennogo sredstva - ingamina na modeli neinfektsionnogo vospaleniya legkikh", FARMAKOLOGIYA, MOSCOW, vol. 67, no. 4, 2004, pages 30 - 34, XP008150961 *
KOVALEVA V.L. ET AL.: "The protector properties of a pseudopeptide drug ingamine studied on a model of bronchospasm in guinea pigs", EKSP. KLIN. FARMAKOL., vol. 68, no. 2, March 2005 (2005-03-01) - April 2005 (2005-04-01), pages 21 - 24, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=15934361> *

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120129908A1 (en) * 2009-05-21 2012-05-24 Vladimir Evgenievich Nebolsin Agent For The Prophylaxis And Treatment Of Highly Pathogenic Infectious Diseases
US9504673B2 (en) * 2009-05-21 2016-11-29 LTD “Valenta-Intellekt” Agent for the prophylaxis and treatment of highly pathogenic infectious diseases
KR20140107190A (ko) * 2011-10-11 2014-09-04 엘티디 "발렌타-인텔렉트" 글루타릴 히스타민의 기도 질환 치료 용도
KR102007280B1 (ko) 2011-10-11 2019-08-06 엘티디“발렌타-인텔렉트” 글루타릴 히스타민의 기도 질환 치료 용도
WO2014035297A1 (fr) * 2012-08-30 2014-03-06 Общество С Ограниченной Ответственностью "Фарминтерпрайсез" Procédé et agent thérapeutique pour la prévention et le traitement des maladies provoquées par des virus contenant des (+) arn
CN104684569A (zh) * 2012-08-30 2015-06-03 制药有限责任公司 用于治疗和预防由含有(+)rna之病毒引起的疾病的方法和药剂
US9820970B2 (en) 2012-08-30 2017-11-21 Obschestvo S Ogranichennoi Otvetstvennostiyu “Pharmenterprises” Method and agent for the treatment and prophylaxis of diseases caused by (+)RNA-containing viruses
EA028541B1 (ru) * 2012-08-30 2017-11-30 Общество С Ограниченной Ответственностью "Фарминтерпрайсез" Способ лечения и профилактики заболеваний, вызываемых (+)рнк-содержащими вирусами
CN104684569B (zh) * 2012-08-30 2018-03-02 制药有限责任公司 用于治疗和预防由含有(+)rna之病毒引起的疾病的方法和药剂
CN103382179A (zh) * 2013-06-05 2013-11-06 四川百利药业有限责任公司 英加韦林的多晶型物及其制备方法

Also Published As

Publication number Publication date
EA200900464A1 (ru) 2009-10-30
EA016363B1 (ru) 2012-04-30
RU2006133521A (ru) 2008-03-27
RU2338552C2 (ru) 2008-11-20

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