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WO2000058022A1 - Procede et appareil de nebulisation d'un liquide particulierement utile a l'administration d'agents biopharmaceutiques en aerosol - Google Patents

Procede et appareil de nebulisation d'un liquide particulierement utile a l'administration d'agents biopharmaceutiques en aerosol Download PDF

Info

Publication number
WO2000058022A1
WO2000058022A1 PCT/IL2000/000181 IL0000181W WO0058022A1 WO 2000058022 A1 WO2000058022 A1 WO 2000058022A1 IL 0000181 W IL0000181 W IL 0000181W WO 0058022 A1 WO0058022 A1 WO 0058022A1
Authority
WO
WIPO (PCT)
Prior art keywords
rigid porous
reservoir
porous body
liquid
aerosol
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/IL2000/000181
Other languages
English (en)
Inventor
Matitiau Fichman
Boris Goldman
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.)
LIPOSOL Ltd
Original Assignee
LIPOSOL Ltd
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 LIPOSOL Ltd filed Critical LIPOSOL Ltd
Priority to AU33219/00A priority Critical patent/AU3321900A/en
Publication of WO2000058022A1 publication Critical patent/WO2000058022A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
    • A61M11/005—Sprayers or atomisers specially adapted for therapeutic purposes using ultrasonics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
    • A61M11/001—Particle size control
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B17/00—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups
    • B05B17/04—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B17/00—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups
    • B05B17/04—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods
    • B05B17/06—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods using ultrasonic or other kinds of vibrations
    • B05B17/0607—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods using ultrasonic or other kinds of vibrations generated by electrical means, e.g. piezoelectric transducers
    • B05B17/0615—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods using ultrasonic or other kinds of vibrations generated by electrical means, e.g. piezoelectric transducers spray being produced at the free surface of the liquid or other fluent material in a container and subjected to the vibrations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A61M15/0085—Inhalators using ultrasonics

Definitions

  • the present invention relates to a method and apparatus for nebulizing a liquid to produce a small-particle aerosol.
  • the invention is particularly useful for the aerosol delivery of biopharmaceuticals, and is therefore described below with respect to this application.
  • nebulizing liquids Many techniques are known for nebulizing liquids.
  • high pressure air is forced through a nozzle to exit in the form of a high-velocity jet which creates a low-pressure region, causing the liquid to be nebulized to rise in a feed tube and to be sheared into droplets.
  • a nebulizer is not suitable for the aerosol delivery of biopharmaceuticals since it produces high shear stresses which degrade or destroy the pharmaceuticals within the droplets.
  • the resulting droplets cover a wide range of particle sizes.
  • Another known technique is a bubbling technique, in which bubbles are formed by passing air through a medium-velocity fretted disc immersed in the liquid near the bottom of the reservoir, to produce bubbles which burst and are dried by tangential injection of drying air.
  • the droplets rapidly shrink in size and are carried out of the generator in an upward swirl ingly motion.
  • a drawback of such an aerosol generator is the difficulty in controlling the size distribution range of the particles in the aerosol.
  • An object of the present invention is to provide a method and apparatus for nebulizing liquids having advantages in the above respects. More particularly, an object of the present invention is to provide a method and apparatus for nebulizing liquids which produce relatively low stresses in the particles of the produced aerosol, and which also permit close control of the particle size distribution, such as to make the method and apparatus especially (but not exclusively) useful for the aerosol delivery of biopharmaceuticals.
  • a method for nebulizing a liquid to produce a small -particle aerosol comprising: providing a reservoir with a rigid porous body; introducing liquid to be nebulized into the reservoir to contact the upper face of the rigid porous body; introducing a pressurized gas to be applied to another face of the rigid porous body; and vibrating the rigid porous body at an ultrasonic frequency.
  • the rigid porous body is a microporous body having pores of micron size, up to several hundred microns in size.
  • the rigid porous body is a ceramic, glass, or a metal .
  • the rigid porous body is vibrated by a pizeoelectric mechanism.
  • the rigid porous body is vibrated by a pizeoelectric device in contact with the rigid porous body.
  • the rigid porous body may also be vibrated by a pizeoelectric material incorporated in a porous matrix and integrated with the rigid porous body according to known techniques as will be described more ful ly below.
  • an aerosol generator for nebulizing a liquid to produce a smal 1 -particle aerosol, comprising: a reservoir for receiving liquid to be nebulized; a rigid porous body within the reservoir; a liquid inlet for introducing liquid to be nebulized into the reservoir to contact the upper face of the rigid porous body therein; a source of pressurized gas for introducing a pressurized gas into the reservoir to be applied to another face of the rigid porous body; and a vibrator for vibrating the rigid porous body at an ultrasonic frequency.
  • the liquid introduced in the reservoir is preferably a mixture of the biopharmaceutical and a liposome in a buffered solution.
  • Fig. 1 is a block diagram illustrating one form of aerosol generator constructed in accordance with the present invention
  • Fig. 2 is a block diagram illustrating modifications in the construction of the aerosol generator of Fig. 1;
  • Fig. 3 and Fig. 4 are block diagrams illustrating two further modifications int he construction of the aerosol generator.
  • the aerosol generator illustrated in Fig. 1 comprise a reservoir 2 provided with a rigid microporous body 3 and a piezoelectric device 4.
  • the rigid microporous body 3 is in the form of a layer secured within reservoir 2 slightly raised from its bottom wall 2a, so as to define a chamber 5 above the microporous layer 3, and another chamber 6 below the microporous layer.
  • Reservoir 2 is provided with an inlet, shown at 7 in a top wall 2b for inletting the liquid to be nebulized, and with an outlet 8 for outletting the nebulized liquid in the form of a small -particle aerosol.
  • outlet 8 includes a face mask 9 to be applied over the face of the patient.
  • the piezoelectric device 4 is in contact with the rigid microporous layer 3 so as to vibrate that layer by ultrasonic vibrations. Piezoelectric device 4 is driven by an electrical power supply, schematically shown by block 10, under the control of a control circuit, schematically shown by block 11.
  • Chamber 6 underlying the rigid microporous layer 3 within reservoir 2 includes an inlet 12 for inletting the compressed air into chamber 6.
  • the compressed air is supplied by a compressor 13 via a conduit 14 and is also under the control of the control circuit 11.
  • the liquid to be nebulized is introduced via inlet 7 into chamber 5 so as to contact the upper face of the rigid microporous layer 3, whereas the compressed air is introduced into chamber 6 so that it is applied to the lower face of the rigid microporous layer 3. Accordingly, when the piezoelectric device 4 is driven at ultrasonic frequencies, the vibrations produced by it, as applied to the microporous layer 3, generate a small-particle aerosol within chamber 5 which is outletted via the outlet 8.
  • the frequency and intensity at which the piezoelectric device 4 is driven by the driving unit 10, and the rate of air flow from the compressor 13, can be controlled to provide the desired particle size, particle size distribution, and flow rate in the produced aerosol.
  • the shear stresses in the particles in the produced aerosol are relatively low as compared to the other known techniques briefly described above.
  • the control circuit shown by block 11 in Fig. 1 could be a personal computer.
  • the parameters concerning the aerosol to be delivered e.g., particle size, delivery rate, delivery period, etc.
  • the piezoelectric driver 10 would be operated within the range of from 10 to 100 KHz, with an output power of from 100 milliwatts to a few watts.
  • the microporous layer 3 is preferably a microporous ceramic or glass, but could also be a microporous metal.
  • the pores are of micron size, up to several hundred microns.
  • the microporous layer may incorporate piezoelectric material within it.
  • a porous ceramic material may be imparted with piezoelectric properties by incorporating piezoelectric material within a porous matrix of the ceramic and integrating it into a rigid microporous body.
  • Fig. 2 illustrates an aerosol generator including such a rigid microporous body incorporating piezoelectric material within it, rather than providing a separate piezoelectric device in contact with the rigid microporous body.
  • the generator illustrated in Fig. 2 includes a reservoir 22 containing the integrated rigid microporous body 23 incorporating the piezoelectric material within it, and dividing the interior of the reservoir into an upper liquid compartment 25 and lower air compartment 26.
  • the other elements in Fig. 2 common with those described above in Fig. 1 carry the same reference numerals to facilitate understanding the construction and operation of the generator of Fig. 2.
  • the generator of Fig. 2 includes several other modifications.
  • One such modification is the addition of an air supply inlet 35 for inletting drying air into chamber 25 above the liquid being nebulized, to remove water from the aerosol which is discharged from outlet 8.
  • Another modification is the provision of a heater 36 in the outlet conduit 8 also for removing water from the discharged aerosol.
  • the air generator illustrated in Fig. 2 includes a flow meter 37 in the conduit 14 supplying air from compressor 13 into the air chamber 26 of the reservoir 22.
  • Fig. 3 illustrates a generator similar to that of Fig. 1, except the piezoelectric device 34 is attached directly to the reservoir 2; and
  • Fig. 4 illustrates a similar generator except the piezoelectric device 44 is submerged within the liquid in the reservoir 2.

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)
  • Special Spraying Apparatus (AREA)

Abstract

Procédé et appareil de nébulisation d'un liquide afin de produire un aérosol à fines particules. Le liquide à nébuliser est introduit dans un réservoir (2) contenant un corps rigide poreux (3), afin d'obtenir un contact avec la face supérieure du corps rigide poreux. Du gaz sous pression à la face inférieure du corps rigide poreux (3) et le corps rigide poreux est soumis à des vibrations à une fréquence ultrasonore.
PCT/IL2000/000181 1999-03-28 2000-03-23 Procede et appareil de nebulisation d'un liquide particulierement utile a l'administration d'agents biopharmaceutiques en aerosol Ceased WO2000058022A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU33219/00A AU3321900A (en) 1999-03-28 2000-03-23 A method and apparatus for nebulizing a liquid particularly useful for the aerosol delivery of biopharmaceuticals

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IL12920899A IL129208A0 (en) 1999-03-28 1999-03-28 A method and apparatus for nebulizing a liquid particulary useful for the aerosol delivery of biopharmaceuticals
IL129208 1999-03-28

Publications (1)

Publication Number Publication Date
WO2000058022A1 true WO2000058022A1 (fr) 2000-10-05

Family

ID=11072651

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IL2000/000181 Ceased WO2000058022A1 (fr) 1999-03-28 2000-03-23 Procede et appareil de nebulisation d'un liquide particulierement utile a l'administration d'agents biopharmaceutiques en aerosol

Country Status (3)

Country Link
AU (1) AU3321900A (fr)
IL (1) IL129208A0 (fr)
WO (1) WO2000058022A1 (fr)

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2835435A1 (fr) * 2002-02-01 2003-08-08 Diffusion Tech Francaise Sarl Dispositif de protection du circuit sonique d'un generateur d'aerosol therapeutique
EP1258264A3 (fr) * 2001-05-16 2004-03-31 InAMed GmbH Appareil pour l'administration d'aérosol
EP1358004A4 (fr) * 2001-01-18 2004-04-28 Ultrasonic Dryer Ltd Procede et appareil de production de goutelettes
WO2006006963A3 (fr) * 2004-04-02 2006-06-01 Us Gov Health & Human Serv Systemes et procedes de distribution par aerosols
EP1700614A1 (fr) * 2005-03-08 2006-09-13 Activaero GmbH Dispositif d'inhalation
US7225807B2 (en) 2001-03-15 2007-06-05 Creare Incorporated Systems and methods for aerosol delivery of agents
GB2450536A (en) * 2007-06-29 2008-12-31 John Deal Mist generating device and control means
CN102511425A (zh) * 2011-12-30 2012-06-27 中国水产科学研究院黑龙江水产研究所 用于水产养殖的水中雾化消毒给药的方法
CN102580885A (zh) * 2011-12-30 2012-07-18 中国水产科学研究院黑龙江水产研究所 用于水产养殖的药物超声雾化装置及与其配套使用的容器
KR101309960B1 (ko) * 2010-12-28 2013-09-17 주식회사 포스코 에어로졸 공급장치
CN103345273A (zh) * 2013-07-25 2013-10-09 重庆市正川玻璃有限公司 共振差频玻璃窑炉高温液面监控系统
WO2016059630A1 (fr) * 2014-10-13 2016-04-21 Omega Life Science Ltd. Nébuliseurs et leurs utilisations
JP2016209825A (ja) * 2015-05-11 2016-12-15 国立大学法人群馬大学 気体の微細化装置
US10857311B2 (en) 2010-01-12 2020-12-08 Omega Life Science Ltd. Method and apparatus for producing fine concentrated aerosol
US20210364176A1 (en) * 2018-02-12 2021-11-25 Noritake Co., Limited Liquid atomizing apparatus
CN114191649A (zh) * 2022-01-14 2022-03-18 深圳市威浩康医疗器械有限公司 一种基于静吸复合麻醉靶控智能化方式的装置

Citations (5)

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US3790079A (en) * 1972-06-05 1974-02-05 Rnb Ass Inc Method and apparatus for generating monodisperse aerosol
US3918640A (en) * 1973-06-20 1975-11-11 Stern Freres Sa Mist generator
US4087495A (en) * 1976-03-25 1978-05-02 Mikuni Kogyo Kabushiki Kaisha Ultrasonic air humidifying apparatus
US4708826A (en) * 1985-03-06 1987-11-24 Sharp Kabushiki Kaisha Supersonic humidifier
US4793714A (en) * 1985-12-05 1988-12-27 Achmed N. Sadik Apparatus for mixing fluids

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3790079A (en) * 1972-06-05 1974-02-05 Rnb Ass Inc Method and apparatus for generating monodisperse aerosol
US3918640A (en) * 1973-06-20 1975-11-11 Stern Freres Sa Mist generator
US4087495A (en) * 1976-03-25 1978-05-02 Mikuni Kogyo Kabushiki Kaisha Ultrasonic air humidifying apparatus
US4708826A (en) * 1985-03-06 1987-11-24 Sharp Kabushiki Kaisha Supersonic humidifier
US4793714A (en) * 1985-12-05 1988-12-27 Achmed N. Sadik Apparatus for mixing fluids

Cited By (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1500002B (zh) * 2001-01-18 2011-07-27 超音速干燥机有限公司 产生液滴的方法和设备
EP1358004A4 (fr) * 2001-01-18 2004-04-28 Ultrasonic Dryer Ltd Procede et appareil de production de goutelettes
US6899322B2 (en) 2001-01-18 2005-05-31 Ultrasonic Dryer Ltd. Method and apparatus for production of droplets
AU2002217410B2 (en) * 2001-01-18 2008-05-01 Ultrasonic Dryer Ltd. Method and apparatus for production of droplets
US8544462B2 (en) 2001-03-15 2013-10-01 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services, Centers For Disease Control And Prevention Systems and methods for aerosol delivery of agents
US7225807B2 (en) 2001-03-15 2007-06-05 Creare Incorporated Systems and methods for aerosol delivery of agents
EP1258264A3 (fr) * 2001-05-16 2004-03-31 InAMed GmbH Appareil pour l'administration d'aérosol
FR2835435A1 (fr) * 2002-02-01 2003-08-08 Diffusion Tech Francaise Sarl Dispositif de protection du circuit sonique d'un generateur d'aerosol therapeutique
WO2006006963A3 (fr) * 2004-04-02 2006-06-01 Us Gov Health & Human Serv Systemes et procedes de distribution par aerosols
US7954486B2 (en) 2004-04-02 2011-06-07 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Aerosol delivery systems and methods
US8656908B2 (en) 2004-04-02 2014-02-25 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services, Centers For Disease Control And Prevention Aerosol delivery systems and methods
US7866317B2 (en) 2005-03-08 2011-01-11 Activaero Gmbh Inhalation device
EP1700614A1 (fr) * 2005-03-08 2006-09-13 Activaero GmbH Dispositif d'inhalation
GB2450536B (en) * 2007-06-29 2011-06-15 John Deal Mist generating device and control system
GB2450536A (en) * 2007-06-29 2008-12-31 John Deal Mist generating device and control means
US10857311B2 (en) 2010-01-12 2020-12-08 Omega Life Science Ltd. Method and apparatus for producing fine concentrated aerosol
KR101309960B1 (ko) * 2010-12-28 2013-09-17 주식회사 포스코 에어로졸 공급장치
CN102580885A (zh) * 2011-12-30 2012-07-18 中国水产科学研究院黑龙江水产研究所 用于水产养殖的药物超声雾化装置及与其配套使用的容器
CN102511425B (zh) * 2011-12-30 2013-07-03 中国水产科学研究院黑龙江水产研究所 用于水产养殖的水中雾化消毒给药的方法
CN102511425A (zh) * 2011-12-30 2012-06-27 中国水产科学研究院黑龙江水产研究所 用于水产养殖的水中雾化消毒给药的方法
CN103345273A (zh) * 2013-07-25 2013-10-09 重庆市正川玻璃有限公司 共振差频玻璃窑炉高温液面监控系统
WO2016059630A1 (fr) * 2014-10-13 2016-04-21 Omega Life Science Ltd. Nébuliseurs et leurs utilisations
EP3206740A4 (fr) * 2014-10-13 2018-08-01 Omega Life Science Ltd Nébuliseurs et leurs utilisations
US10052443B2 (en) 2014-10-13 2018-08-21 Omega Life Science Ltd. Nebulizers and uses thereof
US10369301B2 (en) 2014-10-13 2019-08-06 Omega Life Science Ltd. Nebulizers and uses thereof
JP2016209825A (ja) * 2015-05-11 2016-12-15 国立大学法人群馬大学 気体の微細化装置
US20210364176A1 (en) * 2018-02-12 2021-11-25 Noritake Co., Limited Liquid atomizing apparatus
US12152807B2 (en) * 2018-02-12 2024-11-26 Noritake Co., Limited Liquid atomizing apparatus
CN114191649A (zh) * 2022-01-14 2022-03-18 深圳市威浩康医疗器械有限公司 一种基于静吸复合麻醉靶控智能化方式的装置

Also Published As

Publication number Publication date
AU3321900A (en) 2000-10-16
IL129208A0 (en) 2000-02-17

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