US3755557A - Spray vaccines - Google Patents

Spray vaccines Download PDF

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Publication number
US3755557A
US3755557A US00175778A US3755557DA US3755557A US 3755557 A US3755557 A US 3755557A US 00175778 A US00175778 A US 00175778A US 3755557D A US3755557D A US 3755557DA US 3755557 A US3755557 A US 3755557A
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US
United States
Prior art keywords
virus
lecithin
per
vaccines
liquid
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Expired - Lifetime
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US00175778A
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English (en)
Inventor
J Jacobs
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US Philips Corp
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US Philips Corp
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Publication of US3755557A publication Critical patent/US3755557A/en
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/02—Bacterial antigens
    • A61K39/095—Neisseria

Definitions

  • the invention relates to spray vaccines in which the antigen material in a dry form is dispersed in a liquid propellant.
  • the dispersing agent used is not a liquid and at the same time non-ionic compound, but lecithin which is solid and ionic.
  • the invention relates to spray vaccines for medical and veterinary use.
  • British patent specifications Nos. 837,465 and 994,734 describe pharmaceutical sprays in which a powdered medicament is dispersed in a liquid propellant.
  • a medicament formulated in this manner may be introduced into the upper respiratory passages through the pharynx in the form of an aerosol by means of an atomizer.
  • a liquid non-ionic surfaceactive substance is used to form and maintain the dispersion.
  • lecithin which is neither liquid nor non-ionic, may be used for dispersing dry prophylactics (antigens) in a liquid propellant.
  • the invention relates to spray vaccines for medical and veterinary use which are characterized in that dry antigens are dispersed in a liquid propellant by means of lecithin.
  • antigen is used herein to mean both viral and bacterial antigens. It includes both killed and attenuated living viruses and bacteria and also toxoids.
  • Bacteria, microplasmata and viruses of various natures may be worked up into vaccines according to the invention.
  • influenza strains such as A Aichi, A Japan, A Hong Kong, A England, B Africa, B Massachusetts, B Netherlands, para-influenza strains such as types 1, 2 and 3.
  • Adenovirus strains for example types 3, 4 and 7, meashes virus, Poliovirus, tetanus bacteria, diphteria bacteria and whooping cough bacteria, Reovirus, infectious bronchitis virus, bovine viral diarrhea virus, horse influenza virus, Rhino-viruses, rhinopneumonitis virus, Newcastle disease virus, infectious laryngotracheitis virus, canine herpes virus, feline herpes virus, Miyagawanella virus, panleukopenia virus, distemper virus, rabies virus, pseudorabies virus, hogcholera virus, footand mouth disease vircus, vaccinia virus, bue tongue virus, Pasteurella multicida, cocci, such as Staphylococcus aureus, Staphylococcus albus, Streptococcus, Diplococcus pneumoniae, and further Escherichia, for example Escherichia coli, Salmonella, Corynebacteria, Actinobacillus, Hemophilus, Neisseria,
  • vaccine as used in this specification includes both monovalent and polyvalent vaccines.
  • the antigens to be used in the vaccines may be obtained by the methods known for each particular species.
  • the viruses may be obtained by multiplication on incubated eggs or in tissue cultures, possibly after previous attenuation in similar media or in animals.
  • the bacteria are obtained from artificial culture media.
  • Virulent antigen material may be killed by known means, such as formaldehyde, fi-propiolactone, ultraviolet irradiation and heat treatment.
  • the antigen material may be purified by conventional techniques.
  • the antigens must be Worked up in to a vaccine in the dry condition. For this puropse, they are subjected to a freeze-drying treatment, which may be succeeded by a second drying treatment.
  • the second treatment is not always necessary, its use depending upon the conditions in which the material is processed after the freezedrying treatment. If the processing is such as to preclude 0 the absorption of moisture, the second drying treatment may be dispensed with.
  • the second drying treatment may be eifected by storing the antigens several days in a vacuum over a strongly hygroscopic agent such as, for example, concentrated sulphuric acid, CaCO Na SO silica gel, P 0 and the like.
  • the treatment may be shortened by slightly raising the temperature, for example, to the range of about 35 to 50 C.
  • the spray vaccines according to the invention may be obtained by dispersing dry antigen material in a propellant by means of lecithin.
  • the antigen suspension is mixed with lecithin before the freeze-drying process.
  • the lecithin may be added to the antigen material after the freeze-drying process.
  • the amount of lecithin required to disperse the antigen material as a rule is at least 1 mg. per ml. of vaccine liquid. To ensure a higher stability, the amount of lecithin is preferably increased to -10 mg. per ml. However, even greater amounts of, for example, mg. per ml. may be used. The upper limit is determined by the solubility in the liquid propellant. For practical purposes the amount of lecithin may be chosen between 1 and 100 mg. per ml. and preferably between about 10 and 100 mg. per ml. Obviously, in achieving a satisfactory suspension stability the amount of antigen material per ml. also is significant. In any case, the amount of lecithin required may simply be determined.
  • the antigen material is mixed with the liquid propellant in a ratio which yields the desired concentration whilst adding, for example, 10 mg. of lecithin per ml. of suspension.
  • the time which elapses before the suspended material has deposited is determined. If this time is too short, the stability may be increased by adding more lecithin.
  • Suitable propellants are the gases which generally are used in pharmacy and which are liquid under pressure at room temperature.
  • propellants are: halogenated hydrocarbons, such as dichloro-difluoromethane, dichlorotetrafluoroethane, trichloro-mono fluoromethane, dichloromonofiuoromethane, monochlorodifluoromethane, trichlorotrifiuoro ethane, difluoro ethane, mono-chlorotrifluoro-ethane, hydrocarbons, such as butane, isobutane, propane and the like, or mixtures of these substances.
  • mixtures of gases and gases which are liquid at room temperature under pressure may also be used.
  • the invention although of importance for vaccines in general, is of particular importance for vaccines which protect againt infections of the respiratory organs, since especially for this category the use of a vaccine according to the invention enables the antigens to be conveyed to the area of attack of the infection which is to be controlled by the vaccine.
  • the invention is of importance for influenza vaccines, since these aim at the most frequent infection of the respiratory organs.
  • the virus was purified by means of low-speed and highspeed centrifugation at 1,300 and 50,000 g respectively, the latter process being performed in a Sharples centrifuge with a throughput of 1.5 litres per hour.
  • the sediment of the high-speed centrifugation was re-suspended in an isotonic phosphate buffer having a pH of 8.0.
  • isotonic phosphate buffer having a pH of 8.0.
  • 0.03% by weight and subsequently 0.02% by weight of fl-propiolactone was added.
  • the volume, 5 litres, was dialysed against water for three days with the use of a 10-fold volume per litre.
  • the dialysis liquid was renewed once.
  • the sediment of the high-speed centrifugation was re-suspended in an isotonic phosphate buffer having a pH of 8.0 and containing 0.01 M of citrate. At 1,300 g some impurities were still removed by centrifugation. For the purpose of inactivation first 0.03% by weight and then 0.02% by weight of 8- propiolactone was added. The volume, 5 litres, was dialysed against water for three days with the use of a fold volume of water. The dialysis liquid was renewed once.
  • the ratio of the amounts of virus of strain A and strain B was 3:2.
  • CCA virus Per 100 CCA virus 1 mg. of lecithin was added. The assembly was freeze-dried in a Leyboldt type G04 freezedrier, after which the dry substance was suspended in 40% by volume of dichlorodifluoromethane and by volume of trichloromonofluoromethane. The resulting product contained 1,500 CCA of A virus and 1,000 CCA of B virus per ml.
  • a spray vaccine for medical and veterinary use consisting essentially of a dry antigen dispersed as a stable suspension in a pressurized liquid form of a propellant gas with lecithin as suspension stabilizer.
  • the spray vaccine of claim 5 wherein from 10 to 100 mg. of lecithin per ml. is present.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)
US00175778A 1970-08-29 1971-08-27 Spray vaccines Expired - Lifetime US3755557A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
NL7012832A NL7012832A (en, 2012) 1970-08-29 1970-08-29

Publications (1)

Publication Number Publication Date
US3755557A true US3755557A (en) 1973-08-28

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ID=19810895

Family Applications (1)

Application Number Title Priority Date Filing Date
US00175778A Expired - Lifetime US3755557A (en) 1970-08-29 1971-08-27 Spray vaccines

Country Status (7)

Country Link
US (1) US3755557A (en, 2012)
BE (1) BE771918A (en, 2012)
CA (1) CA971480A (en, 2012)
DE (1) DE2141289A1 (en, 2012)
FR (1) FR2103608B1 (en, 2012)
GB (1) GB1302671A (en, 2012)
NL (1) NL7012832A (en, 2012)

Cited By (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4053585A (en) * 1974-06-25 1977-10-11 National Research Development Corporation Immunological preparations
US4223014A (en) * 1978-05-08 1980-09-16 The United States Of America As Represented By The Secretary Of The Interior Spray immunization of fish
US4225583A (en) * 1978-12-07 1980-09-30 Iowa State University Research Foundation, Inc. Intra-respiratory vaccine for prevention of Bordetella bronchiseptica infection and method of use
EP0069407A1 (en) * 1981-06-10 1983-01-12 Duphar International Research B.V Method of immunizing pigs against Aujeszky's disease
WO1985000011A1 (en) * 1983-06-17 1985-01-03 Univ Miami Microdroplets of water-insoluble drugs
US4515777A (en) * 1978-12-20 1985-05-07 Gist-Brocades N.V. Vaccines
US4537768A (en) * 1978-09-14 1985-08-27 Roussel Uclaf Combined vaccine
US4613500A (en) * 1983-03-09 1986-09-23 Teijin Limited Powdery pharmaceutical composition for nasal administration
US4895719A (en) * 1985-05-22 1990-01-23 Liposome Technology, Inc. Method and apparatus for administering dehydrated liposomes by inhalation
US5616329A (en) * 1990-12-04 1997-04-01 Microtek Research And Development Ltd. Spray-dried antigenic products
US20020119199A1 (en) * 1996-08-22 2002-08-29 Indu Parikh Fenofibrate microparticles
US20030013693A1 (en) * 1998-02-11 2003-01-16 Rtp Pharma Inc. Method and composition for treatment of inflammatory conditions
US6576264B1 (en) 1995-10-17 2003-06-10 Skyepharma Canada Inc. Insoluble drug delivery
US20030180755A1 (en) * 2001-11-19 2003-09-25 Robin Hwang Pharmaceutical compositions in particulate form
US6634576B2 (en) 2000-08-31 2003-10-21 Rtp Pharma Inc. Milled particles
US6682761B2 (en) 2000-04-20 2004-01-27 Rtp Pharma, Inc. Water-insoluble drug particle process
US20040086571A1 (en) * 2001-02-22 2004-05-06 Skyepharma Canada Inc. Fibrate-statin combinations with reduced fed-fasted effects
US6979456B1 (en) 1998-04-01 2005-12-27 Jagotec Ag Anticancer compositions
US7041705B2 (en) 1998-08-19 2006-05-09 Jagotec Ag Injectable aqueous dispersions of propofol
US20060210622A1 (en) * 1999-09-21 2006-09-21 Skyepharma Canada Inc. Surface modified particulate compositions of biologically active substances
US7939106B2 (en) 1998-11-20 2011-05-10 Jagotec Ag Process for preparing a rapidly dispersing solid drug dosage form
US8206746B2 (en) 1996-08-22 2012-06-26 Jagotec Ag Microparticles of water-insoluble substances
US8415329B1 (en) 1998-05-29 2013-04-09 Jagotec Ag Thermoprotected compositions and process for terminal steam sterilization of microparticle preparations
US8586094B2 (en) 2000-09-20 2013-11-19 Jagotec Ag Coated tablets
US9827299B2 (en) * 2009-10-09 2017-11-28 Children's Medical Center Corporation Selectively disrupted whole-cell vaccine
CN107475204A (zh) * 2017-08-03 2017-12-15 中国人民解放军军事医学科学院军事兽医研究所 一种囊膜病毒保护剂及其制备方法

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2423217A2 (fr) * 1978-03-10 1979-11-16 Anvar Procede de vaccination contre la myxomatose
GB8322178D0 (en) * 1983-08-17 1983-09-21 Sterwin Ag Preparing aerosol compositions
GB8502892D0 (en) * 1985-02-05 1985-03-06 Sterwin Ag Aerosol composition
ATE503491T1 (de) * 2003-02-13 2011-04-15 Becton Dickinson Co Verbesserte anthraximpfstoffe und abgabeverfahren
CN103386125A (zh) * 2012-05-08 2013-11-13 刘江秋 肾综合征出血热鼻黏膜免疫气溶胶疫苗的研制

Cited By (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4053585A (en) * 1974-06-25 1977-10-11 National Research Development Corporation Immunological preparations
US4223014A (en) * 1978-05-08 1980-09-16 The United States Of America As Represented By The Secretary Of The Interior Spray immunization of fish
US4537768A (en) * 1978-09-14 1985-08-27 Roussel Uclaf Combined vaccine
US4225583A (en) * 1978-12-07 1980-09-30 Iowa State University Research Foundation, Inc. Intra-respiratory vaccine for prevention of Bordetella bronchiseptica infection and method of use
US4515777A (en) * 1978-12-20 1985-05-07 Gist-Brocades N.V. Vaccines
EP0069407A1 (en) * 1981-06-10 1983-01-12 Duphar International Research B.V Method of immunizing pigs against Aujeszky's disease
US4613500A (en) * 1983-03-09 1986-09-23 Teijin Limited Powdery pharmaceutical composition for nasal administration
WO1985000011A1 (en) * 1983-06-17 1985-01-03 Univ Miami Microdroplets of water-insoluble drugs
US4622219A (en) * 1983-06-17 1986-11-11 Haynes Duncan H Method of inducing local anesthesia using microdroplets of a general anesthetic
US4895719A (en) * 1985-05-22 1990-01-23 Liposome Technology, Inc. Method and apparatus for administering dehydrated liposomes by inhalation
US5616329A (en) * 1990-12-04 1997-04-01 Microtek Research And Development Ltd. Spray-dried antigenic products
US20040018229A1 (en) * 1995-10-17 2004-01-29 Henriksen Inge B. Insoluble drug delivery
US6974593B2 (en) 1995-10-17 2005-12-13 Jagotec Ag Insoluble drug delivery
US6576264B1 (en) 1995-10-17 2003-06-10 Skyepharma Canada Inc. Insoluble drug delivery
US8206746B2 (en) 1996-08-22 2012-06-26 Jagotec Ag Microparticles of water-insoluble substances
US20020119199A1 (en) * 1996-08-22 2002-08-29 Indu Parikh Fenofibrate microparticles
US7255877B2 (en) 1996-08-22 2007-08-14 Jagotec Ag Fenofibrate microparticles
US20030013693A1 (en) * 1998-02-11 2003-01-16 Rtp Pharma Inc. Method and composition for treatment of inflammatory conditions
US6979456B1 (en) 1998-04-01 2005-12-27 Jagotec Ag Anticancer compositions
US8415329B1 (en) 1998-05-29 2013-04-09 Jagotec Ag Thermoprotected compositions and process for terminal steam sterilization of microparticle preparations
US7097849B2 (en) 1998-08-19 2006-08-29 Jagotec Ag Injectable aqueous dispersions of propofol
US7041705B2 (en) 1998-08-19 2006-05-09 Jagotec Ag Injectable aqueous dispersions of propofol
US7939106B2 (en) 1998-11-20 2011-05-10 Jagotec Ag Process for preparing a rapidly dispersing solid drug dosage form
US7939105B2 (en) 1998-11-20 2011-05-10 Jagotec Ag Process for preparing a rapidly dispersing solid drug dosage form
US20060210622A1 (en) * 1999-09-21 2006-09-21 Skyepharma Canada Inc. Surface modified particulate compositions of biologically active substances
US6682761B2 (en) 2000-04-20 2004-01-27 Rtp Pharma, Inc. Water-insoluble drug particle process
US6634576B2 (en) 2000-08-31 2003-10-21 Rtp Pharma Inc. Milled particles
US8703202B2 (en) 2000-09-20 2014-04-22 Jagotec Ag Coated tablets
US8586094B2 (en) 2000-09-20 2013-11-19 Jagotec Ag Coated tablets
US20040086571A1 (en) * 2001-02-22 2004-05-06 Skyepharma Canada Inc. Fibrate-statin combinations with reduced fed-fasted effects
US20030186271A1 (en) * 2001-11-19 2003-10-02 Robin Hwang Pharmaceutical compositions in particulate form
US7842310B2 (en) 2001-11-19 2010-11-30 Becton, Dickinson And Company Pharmaceutical compositions in particulate form
US20030180755A1 (en) * 2001-11-19 2003-09-25 Robin Hwang Pharmaceutical compositions in particulate form
US20070190158A1 (en) * 2001-11-19 2007-08-16 Becton Dickinson And Company Pharmaceutical compositions in particulate form
US9827299B2 (en) * 2009-10-09 2017-11-28 Children's Medical Center Corporation Selectively disrupted whole-cell vaccine
CN107475204A (zh) * 2017-08-03 2017-12-15 中国人民解放军军事医学科学院军事兽医研究所 一种囊膜病毒保护剂及其制备方法

Also Published As

Publication number Publication date
NL7012832A (en, 2012) 1972-03-02
FR2103608A1 (en, 2012) 1972-04-14
BE771918A (fr) 1972-02-28
GB1302671A (en, 2012) 1973-01-10
CA971480A (en) 1975-07-22
DE2141289A1 (de) 1972-03-09
FR2103608B1 (en, 2012) 1975-02-07

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