WO2014103488A1 - 経鼻インフルエンザワクチン組成物 - Google Patents
経鼻インフルエンザワクチン組成物 Download PDFInfo
- Publication number
- WO2014103488A1 WO2014103488A1 PCT/JP2013/078721 JP2013078721W WO2014103488A1 WO 2014103488 A1 WO2014103488 A1 WO 2014103488A1 JP 2013078721 W JP2013078721 W JP 2013078721W WO 2014103488 A1 WO2014103488 A1 WO 2014103488A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- spray
- influenza
- vaccine composition
- administered
- nasal
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 49
- 229960003971 influenza vaccine Drugs 0.000 title claims abstract description 46
- 239000002245 particle Substances 0.000 claims abstract description 45
- 241000712461 unidentified influenza virus Species 0.000 claims abstract description 32
- 229920002125 Sokalan® Polymers 0.000 claims abstract description 22
- 239000002671 adjuvant Substances 0.000 claims abstract description 20
- 229940041676 mucosal spray Drugs 0.000 claims abstract description 19
- 239000007921 spray Substances 0.000 claims description 58
- 229960005486 vaccine Drugs 0.000 claims description 51
- 241000700605 Viruses Species 0.000 claims description 27
- 238000010008 shearing Methods 0.000 claims description 17
- 239000011550 stock solution Substances 0.000 claims description 16
- 238000009826 distribution Methods 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 11
- 206010022000 influenza Diseases 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 7
- 238000009472 formulation Methods 0.000 claims description 6
- 238000002347 injection Methods 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- 210000002850 nasal mucosa Anatomy 0.000 claims description 4
- 238000005507 spraying Methods 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 3
- 239000000427 antigen Substances 0.000 abstract description 15
- 102000036639 antigens Human genes 0.000 abstract description 15
- 108091007433 antigens Proteins 0.000 abstract description 15
- 239000000499 gel Substances 0.000 description 32
- 230000000052 comparative effect Effects 0.000 description 22
- 238000011081 inoculation Methods 0.000 description 18
- 230000028993 immune response Effects 0.000 description 9
- 230000000694 effects Effects 0.000 description 6
- 230000003472 neutralizing effect Effects 0.000 description 6
- 238000007920 subcutaneous administration Methods 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 210000004877 mucosa Anatomy 0.000 description 3
- 210000001331 nose Anatomy 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 230000000091 immunopotentiator Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 210000003928 nasal cavity Anatomy 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- -1 Carboxyvinyl Chemical group 0.000 description 1
- 108010012253 E coli heat-labile enterotoxin Proteins 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 229920002148 Gellan gum Polymers 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229940124873 Influenza virus vaccine Drugs 0.000 description 1
- 241001500351 Influenzavirus A Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000010492 gellan gum Nutrition 0.000 description 1
- 239000000216 gellan gum Substances 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000000379 polymerizing effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000001932 seasonal effect Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 229940031626 subunit vaccine Drugs 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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
- A61K39/12—Viral antigens
- A61K39/145—Orthomyxoviridae, e.g. influenza virus
-
- 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
- A61K39/12—Viral antigens
-
- 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
-
- 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
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- 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
- A61K9/0043—Nose
-
- 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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- 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
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/525—Virus
- A61K2039/5252—Virus inactivated (killed)
-
- 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
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
- A61K2039/541—Mucosal route
- A61K2039/543—Mucosal route intranasal
-
- 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
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55555—Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/16011—Orthomyxoviridae
- C12N2760/16111—Influenzavirus A, i.e. influenza A virus
- C12N2760/16121—Viruses as such, e.g. new isolates, mutants or their genomic sequences
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/16011—Orthomyxoviridae
- C12N2760/16111—Influenzavirus A, i.e. influenza A virus
- C12N2760/16134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/16011—Orthomyxoviridae
- C12N2760/16211—Influenzavirus B, i.e. influenza B virus
- C12N2760/16234—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
Definitions
- the present invention relates to a nasal mucosal spray administration type influenza vaccine composition.
- Influenza is an acute respiratory infection caused by influenza virus, and it is prevalent every year especially in winter. In addition, it may become a global pandemic, often leading to serious death. Influenza is known to have a certain preventive effect by inoculating an influenza vaccine, and it is widely inoculated before the epidemic period.
- influenza vaccines that are inoculated subcutaneously with inactivated protein components of influenza virus antigens are approved in Japan, and this split vaccine is currently used as a seasonal influenza vaccine.
- Such a subcutaneous inoculation vaccine is highly effective in preventing the severity of influenza such as pneumonia, but it has a low ability to induce antibodies in the upper respiratory tract mucosa, which is the site of influenza virus infection, and it can be said that its protective effect is sufficient. Absent.
- Patent Document 1 discloses a nasal influenza vaccine containing an adjuvant, and it has been shown that the ability to induce immunity is improved by including an adjuvant. There is concern about toxicity.
- nasal vaccine as a next-generation influenza vaccine is desired from the conventional influenza vaccine inoculated subcutaneously or intramuscularly.
- problems for practical use such as how to suppress the toxicity of the adjuvant used in the drug.
- An object of the present invention is to use a nasal mucosal spray administration type which is effective with a small amount of antigen and has little side effect reaction without using an adjuvant, using an influenza virus inactivated whole particle vaccine which has been previously approved and used as an antigen. It is providing the influenza vaccine composition, its manufacturing method, and the prevention method of influenza.
- a nasal mucosal spray administration gel base comprising a carboxyvinyl polymer treated by applying a shearing force from the outside in order to add spray performance is not affected by influenza virus. It has been found that the ability to induce immunity to humans can be enhanced without using an adjuvant by combining with an activated whole particle vaccine, and the present invention has been completed. That is, the present invention is as follows.
- [1] comprising a gel base containing (i) whole particles inactivated by influenza virus, and (ii) a carboxyvinyl polymer treated with an external shearing force to add spray performance,
- a nasal mucosal spray administration type influenza vaccine composition characterized by not containing an adjuvant.
- influenza virus inactivated whole particles of (i) are 1 to 500 ⁇ g HA / mL per vaccine virus strain.
- [4] Carboxyvinyl treated with an external shear force to add (1) formulation particle size distribution range, (2) spray density uniformity, and / or (3) injection angle control as spray performance
- the nasal mucosal spray administration type influenza vaccine composition according to any one of [1] to [3], wherein a spray administration gel base containing a polymer is used.
- the preparation average particle size is in the range of 30 ⁇ m to 80 ⁇ m, and the particle size distribution is in the range of 10 ⁇ m to 100 ⁇ m, 80% or more
- the spray density is a uniform full cone with no bias
- the preparation average particle size is in the range of 40 ⁇ m to 70 ⁇ m, and the particle size distribution is in the range of 10 ⁇ m to 100 ⁇ m, 90% or more
- the spray density is a uniform full cone with no bias
- the nasal mucosal spray-administered influenza vaccine composition according to any one of [1] to [7], which uses a spray-administered gel base containing a carboxyvinyl polymer that has been treated by applying a shearing force from the outside.
- the nasal mucosal spray-administered influenza vaccine composition according to any one of [1] to [8] can be sprayed from each nostril to the intranasal mucosa to a subject in need thereof
- a method of preventing influenza comprising administering using a device.
- influenza virus inactivated whole particles are used as an active ingredient, an effective immune response is induced with a smaller amount of antigen without using an adjuvant, and no nasal agent has fewer side effects since no adjuvant is used.
- a mucosal spray-administered influenza vaccine composition can be provided, and an influenza epidemic can be dealt with accurately.
- the nasal mucosal spray administration type influenza vaccine composition of the present invention contains a nasal mucosal spray administration gel base composed of a carboxyvinyl polymer processed by applying an external shearing force in order to add spray performance. By spreading and staying in the mucous membrane for a long time, an effective immune response can be induced with a smaller amount of antigen.
- the antigenicity of virus-inactivated whole particles can be favorably maintained because it can be processed in a short time without applying stress, and effective immunization
- a nasal mucosal spray-administered influenza vaccine composition that induces a response and has few side effects can be provided.
- an adjuvant that is an immunopotentiator is not included, but the upper airway mucosa and systemic immunity induction equivalent to or stronger than those of a composition comprising an influenza virus vaccine and an adjuvant can be provided.
- the present invention is characterized in that an nasal mucosal spray administration gel base composed of a carboxyvinyl polymer treated with an external shearing force to add spray performance and an adjuvant containing influenza virus inactivated whole particles are not used.
- a nasal mucosal spray administration type influenza vaccine composition is provided.
- the “gel base containing a carboxyvinyl polymer treated by applying an external shearing force to add spray performance” used in the present invention refers to, for example, “skin / mucosal adhesive agent disclosed in WO2007 / 123193.
- the term “containing gel base” means a base containing a carboxyvinyl polymer, containing gellan gum as appropriate, and adjusting the viscosity by applying a shearing force from the outside. Such a base is characterized in that it can be adjusted to various viscosities by applying a shearing force from the outside, and can be managed so that the spray angle and spray density from the spray container are suitable for the purpose.
- an upper exhaust airless spray container is used as a multi-dose spray container as described in WO2007 / 123193 and WO2007 / 123207.
- the spray container can be used without any remaining amount in any angle or range of angles, and the object can be achieved.
- the spreadability of influenza virus inactivated whole particles on the nasal mucosa is improved over a wide range for a long time, thereby increasing the immunogenicity of the vaccine. It is.
- Carboxyvinyl polymer which is the raw material for nasal mucosal spray administration, is a hydrophilic polymer obtained by polymerizing acrylic acid as the main component, and limits the pharmaceutical additives normally used to prepare aqueous gels. It can be used without.
- the content of the gel base containing the carboxyvinyl polymer treated by applying an external shearing force in order to add spray performance is 0.1 to 1.0% w / v in terms of the content of carboxyvinyl polymer. Preferably, it is 0.3 to 0.7 w / v%.
- influenza virus inactivated whole particles used in the present invention refer to virus particles purified from a virus suspension obtained by culturing influenza virus while retaining the virus form. Therefore, the influenza vaccine of the present invention means a vaccine excluding split vaccines containing subvirions and subunit vaccines containing purified HA or NA, and is also referred to as whole particle vaccines.
- the whole influenza virus inactivated particles are preferably purified from a virus suspension in the absence of a surfactant and ethers.
- a virus solution containing inactivated influenza virus whole particles purified or concentrated for mixing with a nasal mucosal spray administered gel base is referred to as a virus stock solution.
- the concentration of influenza virus inactivated total particles is preferably 1 to 500 ⁇ g HA / mL (HA conversion) per vaccine virus strain, more preferably 20 to 250 ⁇ g HA / mL (HA conversion). The concentration can be obtained by measuring the concentration of HA protein.
- influenza viruses include all currently known types and subtypes, as well as types and subtypes that will be isolated and identified in the future. In addition, no epidemic has been observed in humans so far, and from the viewpoint of effectively preventing human infection in the future, H1 to 16 excluding H1 and H3 of influenza virus A (ie, H2 And a subtype consisting of a combination of a subtype selected from H4 to 16) and a subtype selected from N1 to 9 is preferred. These subtypes are also referred to as new influenza viruses.
- the subtype is more preferably a combination of a subtype selected from H5, 7 and 9 and a subtype selected from N1-9.
- An influenza virus may be one strain belonging to the same subtype, two or more strains belonging to the same subtype, or two or more strains belonging to different subtypes. May be.
- influenza virus may be a strain isolated from an infected animal or patient, or may be a recombinant virus established by genetic engineering in cultured cells.
- the influenza virus can be cultured by inoculating the virus into the allantoic cavity of chicken eggs and culturing by infecting cultured cells.
- Adjuvant is a general term for substances that have regulatory activities such as enhancement and suppression of immune response, and is an immunopotentiator added to vaccines to enhance the immunogenicity of antigens. Many substances have been studied so far Has been. On the other hand, the use of an adjuvant improves the immune effect of the vaccine, but also has a drawback that side effects such as inflammation may occur. Of course, several candidates are available as adjuvants for nasal vaccines, but there are no adjuvants that have been widely recognized as safe. No nasal vaccine has yet been approved.
- the present inventor can use a nasal mucosal spray administration gel base having excellent spray performance as described above with a high nasal mucosal spread rate for the whole particle vaccine, thereby reducing the amount without using an adjuvant.
- a vaccine with an antigen amount that is effective and has few side effects can be obtained.
- the average particle size of the sprayed product is in the range of 30 ⁇ m to 80 ⁇ m (preferably 40 ⁇ m Device with an appropriate range of 80 to 70 ⁇ m (preferably 90% to a range of 10 ⁇ m to 100 ⁇ m), and a particle size distribution of 80 ⁇ m or more (preferably 90% to a range of 10 ⁇ m to 100 ⁇ m).
- the spray angle from 30 ° to 70 ° (preferably in the range of 40 ° to 60 °), and the spray density to the nose evenly Possible find nasal mucosal spray administration influenza vaccine composition spray administered within, leading to the present invention by discovering their preparation as well as prevention method using the same.
- the vaccine of the present invention may further contain a pharmaceutically acceptable carrier in addition to the influenza virus inactivated whole particles and the nasal mucosal spray administration gel base.
- a pharmaceutically acceptable carrier in addition to the influenza virus inactivated whole particles and the nasal mucosal spray administration gel base.
- carriers commonly used in the production of vaccines and intranasal preparations can be used. Specifically, saline, buffered saline, dextrose, water, glycerin, isotonic aqueous buffer And combinations thereof. Further, a preservative (eg, thimerosal), an isotonic agent, a pH adjuster, a surfactant, an inactivating agent (eg, formalin) and the like are appropriately blended therein.
- the vaccine of the present invention is sprayed into the nasal cavity.
- the vaccine of the present invention can be used to prevent or reduce symptoms of influenza.
- a multi-dose spray nasal container or a sprayable device that does not have a pump function for both nostrils, and generally a sprayable disposable device that does not have a pump function can be used.
- the dosage is determined in consideration of the age, sex, body weight, etc. of the subject, but usually 1 to 150 ⁇ g HA, preferably 5 to 50 ⁇ g HA per one vaccine virus strain is administered as an antigen once or twice or more. can do.
- the administration is preferably performed a plurality of times. In this case, administration is preferably performed with an interval of 1 to 4 weeks.
- a gel base and three types of virus stock solutions were prepared by the following method, and both were mixed as follows to prepare an influenza vaccine composition as an example.
- Influenza vaccine compositions not containing a gel base were prepared with the compositions shown in the following table using the inactivated whole particle antigens used in the above examples as appropriate, and were designated as Comparative Examples 1 to 4. Comparative Example 1
- Example 1 The influenza vaccine composition prepared in Example 1 and Comparative Example 1 was sprayed by nasal spray inoculation of 0.25 mL of one nose in a suitable disposable device for each of four adult volunteers at a 3-week interval for a total of 2 times. The total nostril was 45 ⁇ g HA). Blood was collected over time and nasal washes were collected, and the neutralizing antibody titer against the vaccine strain was measured and evaluated. The results are shown in Table 1 for Example 1 and Table 2 for Comparative Example 1.
- Example 1 vaccine virus stock solution + spray administration gel base
- Comparative Example 1 vaccine inactivated split influenza virus antigen composition not containing gel base
- serum neutralizing antibody Although no increase in antibody titer was observed at 3/4, an increase in antibody titer was observed at 4/4 in Example 1 vaccine, indicating that the level was also significant.
- An increase in the neutralizing antibody titer of the nasal wash was observed in all cases in Example 1 and Comparative Example 1, but it was confirmed that Example 1 had a greater degree.
- Influenza vaccine compositions prepared in Example 2 and Comparative Example 2 were used in appropriate disposable devices, respectively, for adult volunteers, Example 2: 25 people, Comparative Example 2: 24 people, two times at intervals of 3 weeks, and further About half a year later, a total of 3 times, nasal 0.25 mL was inoculated intranasally (both nares total 45 ⁇ g HA). Three weeks after the third inoculation, blood was collected and the nasal wash was collected, and the neutralizing antibody titer against the vaccine strain was measured and evaluated. The results are shown in Table 3.
- Example 2 vaccine virus stock solution + spray administration gel base
- Comparative Example 2 vaccine virus stock solution only
- Example 2 vaccine containing spray administration gel base was compared with Comparative Example 2 vaccine.
- the response was clearly higher. It is said that the immune response in naive humans (infants / children) who are in contact with influenza virus antigens for the first time is difficult to be induced, and the immune response in naive individuals is high, which many healthy adults have never contacted. It can be estimated by examining the antibody response to the vaccine of pathogenic avian influenza virus (H5N1 strain).
- Example 2 vaccine virus stock solution + spray administration gel base
- Example 3 The influenza vaccine compositions prepared in Example 3, Comparative Example 3 and Comparative Example 4 were treated with an appropriate volunteer device and subcutaneous inoculation, respectively, for adult volunteers, Example 3-nasal inoculation: 26 persons, Comparative Example 3- Nasal inoculation: nasal instillation of 0.25 mL of one nose (25 ⁇ g HA / strain / 0.5 mL in total for both nares) and Comparative Example 4 (current vaccine) —subcutaneous inoculation: 38 Once per name, 0.5 mL was inoculated subcutaneously (15 ⁇ g HA / strain / 0.5 mL).
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Organic Chemistry (AREA)
- Pulmonology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Otolaryngology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
アジュバントを含まないことを特徴とする経鼻粘膜スプレー投与型インフルエンザワクチン組成物。
本発明の経鼻粘膜スプレー投与型インフルエンザワクチン組成物は、噴霧性能を付加するために外部からせん断力を与えて処理したカルボキシビニルポリマーからなる経鼻粘膜スプレー投与ゲル基剤を含有するため、鼻腔粘膜に広く長く展着・滞留することにより、より少ない抗原量で有効な免疫応答を誘導可能とする。
本発明の経鼻粘膜スプレー投与型インフルエンザワクチン組成物の製造方法によると、ストレスを与えることなく短時間で処理できるためウイルス不活化全粒子の抗原性を良好に維持することができ、有効な免疫応答を誘導し、かつ、副作用の少ない経鼻粘膜スプレー投与型インフルエンザワクチン組成物を提供することができる。
なお、本発明においては、免疫増強剤であるアジュバントを含まないが、インフルエンザウイルスワクチンとアジュバントからなる組成物と同等、またはより強い上気道粘膜及び全身の免疫誘導を提供できる。
噴霧性能を付加するために外部からせん断力を与えて処理したカルボキシビニルポリマーを含有するゲル基剤の含量は、カルボキシビニルポリマーの含量に換算して、0.1~1.0%w/vであり、好ましくは0.3~0.7w/v%である。
本発明のワクチンを用いて、インフルエンザを予防またはその症状を軽減することができる。
投与量は、対象の年齢、性別、体重等を考慮して決められるが、抗原として、1種のワクチンウイルス株当り通常1~150μg HA、好ましくは5~50μg HAを1回または2回以上投与することができる。好ましくは複数回の投与であり、この場合、1~4週間の間隔をあけて投与することが好ましい。
上記のゲル基剤例1とウイルス原液例1~3をそれぞれ(1:1)の比率で混合撹拌し、均質なインフルエンザワクチン組成物実施例1、実施例2および実施例3を得た。各実施例で得られた組成物の組成およびその物性値/噴霧性能を下表に示す。この混合撹拌はウイルス不活化全粒子抗原にストレスを与えることなく、緩やかな混合撹拌で短時間に達成できる。得られたインフルエンザワクチン組成物の成分分量及び物性値並びに適切なデバイスを用いて噴霧した場合の付加された噴霧性能を示す。
実施例1
実施例1および比較例1で調製されたインフルエンザワクチン組成物を適切な使い捨てデバイスにて、それぞれ成人ボランテア4名ずつに3週間間隔で計2回、片鼻0.25mLを経鼻噴霧接種(両鼻孔合計で45μgHA)した。
継時的に採血と鼻腔洗浄液の回収を行い、ワクチン株に対する中和抗体価を測定し評価した。結果を実施例1については表1に、比較例1については表2に示した。
実施例2および比較例2で調製されたインフルエンザワクチン組成物を適切な使い捨てデバイスにて、それぞれ成人ボランテア、実施例2:25名、比較例2:24名ずつに3週間間隔で2回、更に約半年後に追加して計3回、片鼻0.25mLを経鼻噴霧接種(両鼻孔合計で45μgHA)した。
3回接種3週後に採血と鼻腔洗浄液の回収を行い、ワクチン株に対する中和抗体価を測定し評価した。結果を表3に示した。
初めてインフルエンザウイルス抗原に接触するナイーブな状態にあるヒト(幼児・小児)における免疫応答は誘導されにくいとされており、ナイーブな個体における免疫応答は、多くの健康成人が接触したことがない、高病原性鳥インフルエンザウイルス(H5N1株)のワクチンに対する抗体応答を検討することによって推定できると考えられる。
上記結果が示すとおり、ナイーブな被験者でも、実施例2ワクチン(ウイルス原液+スプレー投与ゲル基剤)の経鼻接種を3回行うことにより、血清および鼻腔洗浄液中に高いレベルの中和抗体価が誘導されることが発見された。
実施例3、比較例3および比較例4で調製されたインフルエンザワクチン組成物を適切な使い捨てデバイスおよび皮下接種にて、それぞれ成人ボランテア、実施例3-経鼻接種:26名、比較例3-経鼻接種:25名ずつに3週間間隔で2回、片鼻0.25mLを経鼻噴霧接種(両鼻孔合計で15μgHA/株/0.5mL)並びに比較例4(現行ワクチン)-皮下接種:38名に1回、0.5mLを皮下接種(15μgHA/株/0.5mL)した。
1回接種又は2回接種3週後に採血と鼻腔洗浄液の回収を行い、ワクチン株に対する中和抗体価を測定し評価した。結果を表4に示した。
Claims (10)
- (i)インフルエンザウイルス不活化全粒子、および(ii)噴霧性能を付加するために外部からせん断力を与えて処理したカルボキシビニルポリマーを含有するゲル基剤を含み、
アジュバントを含まないことを特徴とする経鼻粘膜スプレー投与型インフルエンザワクチン組成物。 - (i)のインフルエンザウイルス不活化全粒子が1種のワクチンウイルス株当り1~500μgHA/mLである請求項1に記載の経鼻粘膜スプレー投与型インフルエンザワクチン組成物。
- 0.1w/v%から1.0w/v%のカルボキシビニルポリマーを含有する、請求項1または2に記載の経鼻粘膜スプレー投与型インフルエンザワクチン組成物。
- 噴霧性能としての、(1)製剤粒度分布範囲、(2)噴霧密度均一性、および/または(3)噴射角度制御を付加するために、外部からせん断力を与えて処理したカルボキシビニルポリマーを含有するスプレー投与ゲル基剤を用いた請求項1~3のいずれかに記載の経鼻粘膜スプレー投与型インフルエンザワクチン組成物。
- 0.5w/v%から2.0w/v%のカルボキシビニルポリマーを含有するゲル基剤を用い、噴霧性能としての、(1)製剤粒度分布範囲、(2)噴霧密度均一性、および/または(3)噴射角度制御を付加するために外部からせん断力を与えて処理し、スプレー投与ゲル基剤を得た後、インフルエンザウイルス不活化全粒子を含むウイルス原液とストレスを与えることなく短時間で均一に混和して得られる、請求項1~4のいずれかに記載の経鼻粘膜スプレー投与型インフルエンザワクチン組成物。
- カルボキシビニルポリマーを含有する基剤に外部からせん断力を与えて、(1)製剤粒度分布において製剤平均粒子径が30μmから80μmの範囲、粒度分布が10μmから100μmの範囲に80%以上であり、(2)噴霧密度が偏りのない均等なフルコーンとなり、(3)噴射角度が30°から70°の範囲に制御した噴霧性能を付加されたスプレー投与ゲル基剤を用いて製造する請求項1~5のいずれかに記載の経鼻粘膜スプレー投与型インフルエンザワクチン組成物。
- カルボキシビニルポリマーを含有する基剤に外部からせん断力を与えて、(1)製剤粒度分布において製剤平均粒子径が40μmから70μmの範囲、粒度分布が10μmから100μmの範囲に90%以上であり、(2)噴霧密度が偏りのない均等なフルコーンとなり、(3)噴射角度が40°から60°の範囲に制御した噴霧性能を付加されたスプレー投与ゲル基剤を用いて製造する請求項1~5のいずれかに記載の経鼻粘膜スプレー投与型インフルエンザワクチン組成物。
- ポンプ機能を有しないスプレー可能なデバイスを用いて噴霧投与を可能とするために、(1)製剤粒度分布範囲、(2)噴霧密度均一性、(3)噴射角度制御を付加するために外部からせん断力を与えて処理したカルボキシビニルポリマーを含有するスプレー投与ゲル基剤を用いた請求項1~7のいずれかに記載の経鼻粘膜スプレー投与型インフルエンザワクチン組成物。
- 請求項1~8のいずれかに記載の経鼻粘膜スプレー投与型インフルエンザワクチン組成物を、それを必要とする対象に、各鼻孔から鼻腔内粘膜に粘稠な製剤を噴霧可能とするデバイスを用いて投与することを含むインフルエンザの予防方法。
- インフルエンザを予防するための、請求項1~8のいずれかに記載の経鼻粘膜スプレー投与型インフルエンザワクチン組成物の使用。
Priority Applications (23)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
MX2015008380A MX371154B (es) | 2012-12-28 | 2013-10-23 | Composicion nasal de vacuna para la influenza. |
CN201380068031.4A CN104884086A (zh) | 2012-12-28 | 2013-10-23 | 经鼻流感疫苗组合物 |
PL13867863T PL2939692T3 (pl) | 2012-12-28 | 2013-10-23 | Kompozycja szczepionki do nosa przeciw grypie |
LTEP13867863.6T LT2939692T (lt) | 2012-12-28 | 2013-10-23 | Nazalinė gripo vakcinos kompozicija |
RU2015130634A RU2652296C2 (ru) | 2012-12-28 | 2013-10-23 | Композиция назальной вакцины против гриппа |
NZ70892213A NZ708922A (en) | 2012-12-28 | 2013-10-23 | Nasal influenza vaccine composition |
DK13867863.6T DK2939692T3 (da) | 2012-12-28 | 2013-10-23 | Nasal influenzavaccinesammensætning |
EP13867863.6A EP2939692B1 (en) | 2012-12-28 | 2013-10-23 | Nasal influenza vaccine composition |
SG11201504648TA SG11201504648TA (en) | 2012-12-28 | 2013-10-23 | Nasal influenza vaccine composition |
BR112015015523-5A BR112015015523B1 (pt) | 2012-12-28 | 2013-10-23 | Composição de vacina nasal para influenza |
EP19167809.3A EP3566715A1 (en) | 2012-12-28 | 2013-10-23 | Nasal influenza vaccine composition |
AU2013367751A AU2013367751B2 (en) | 2012-12-28 | 2013-10-23 | Nasal influenza vaccine composition |
CA2894223A CA2894223C (en) | 2012-12-28 | 2013-10-23 | Nasal influenza vaccine composition |
US14/653,131 US20160015800A1 (en) | 2012-12-28 | 2013-10-23 | Nasal influenza vaccine composition |
SI201331485T SI2939692T1 (sl) | 2012-12-28 | 2013-10-23 | Nazalno cepivo za influenco |
JP2014554202A JP6247639B2 (ja) | 2012-12-28 | 2013-10-23 | 経鼻インフルエンザワクチン組成物 |
KR1020157016766A KR102071099B1 (ko) | 2012-12-28 | 2013-10-23 | 경비 인플루엔자 백신 조성물 |
ES13867863T ES2731899T3 (es) | 2012-12-28 | 2013-10-23 | Composición de vacuna nasal contra la gripe |
IL239284A IL239284B (en) | 2012-12-28 | 2015-06-08 | Nasal flu vaccine compound |
PH12015501482A PH12015501482B1 (en) | 2012-12-28 | 2015-06-26 | Nasal influenza vaccine composition |
HK15110594.2A HK1209646A1 (en) | 2012-12-28 | 2015-10-28 | Nasal influenza vaccine composition |
US16/200,233 US20190091324A1 (en) | 2012-12-28 | 2018-11-26 | Nasal influenza vaccine composition |
CY20191100681T CY1122372T1 (el) | 2012-12-28 | 2019-06-28 | Συνθεση ρινικου εμβολιου γριπης |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2012287900 | 2012-12-28 | ||
JP2012-287900 | 2012-12-28 |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US14/653,131 A-371-Of-International US20160015800A1 (en) | 2012-12-28 | 2013-10-23 | Nasal influenza vaccine composition |
US16/200,233 Division US20190091324A1 (en) | 2012-12-28 | 2018-11-26 | Nasal influenza vaccine composition |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2014103488A1 true WO2014103488A1 (ja) | 2014-07-03 |
Family
ID=51020588
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2013/078721 WO2014103488A1 (ja) | 2012-12-28 | 2013-10-23 | 経鼻インフルエンザワクチン組成物 |
Country Status (27)
Country | Link |
---|---|
US (2) | US20160015800A1 (ja) |
EP (2) | EP3566715A1 (ja) |
JP (1) | JP6247639B2 (ja) |
KR (1) | KR102071099B1 (ja) |
CN (2) | CN104884086A (ja) |
AU (1) | AU2013367751B2 (ja) |
BR (1) | BR112015015523B1 (ja) |
CA (1) | CA2894223C (ja) |
CY (1) | CY1122372T1 (ja) |
DK (1) | DK2939692T3 (ja) |
ES (1) | ES2731899T3 (ja) |
HK (1) | HK1209646A1 (ja) |
HU (1) | HUE044434T2 (ja) |
IL (1) | IL239284B (ja) |
LT (1) | LT2939692T (ja) |
MX (1) | MX371154B (ja) |
MY (1) | MY173503A (ja) |
NZ (1) | NZ708922A (ja) |
PH (1) | PH12015501482B1 (ja) |
PL (1) | PL2939692T3 (ja) |
PT (1) | PT2939692T (ja) |
RU (1) | RU2652296C2 (ja) |
SG (2) | SG10201705190TA (ja) |
SI (1) | SI2939692T1 (ja) |
TR (1) | TR201910293T4 (ja) |
TW (1) | TWI624280B (ja) |
WO (1) | WO2014103488A1 (ja) |
Cited By (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9408880B2 (en) | 2013-12-20 | 2016-08-09 | Katherine Rose Kovarik | Method and system for prevention and treatment of allergic and inflammatory diseases |
US9457077B2 (en) | 2009-11-18 | 2016-10-04 | Katherine Rose Kovarik | Method and system for targeting the microbiome to promote health and treat allergic and inflammatory diseases |
US9585920B2 (en) | 2011-02-04 | 2017-03-07 | Katherine Rose Kovarik | Method and system for treating cancer cachexia |
US9730967B2 (en) | 2011-02-04 | 2017-08-15 | Katherine Rose Kovarik | Method and system for treating cancer cachexia |
EP3162378A4 (en) * | 2014-06-25 | 2018-01-17 | Toko Yakuhin Kogyo Kabushiki Kaisha | Influenza vaccine nasal vaccination system |
WO2019070019A1 (ja) * | 2017-10-05 | 2019-04-11 | 東興薬品工業株式会社 | 経鼻b型肝炎ワクチン組成物およびその製造方法 |
US10314865B2 (en) | 2011-02-04 | 2019-06-11 | Katherine Rose Kovarik | Method and system for treating cancer and other age-related diseases by extending the healthspan of a human |
WO2021002355A1 (ja) | 2019-07-03 | 2021-01-07 | アイリス株式会社 | インフルエンザウイルス感染症を治療するための医薬組成物 |
US11020346B2 (en) | 2014-06-25 | 2021-06-01 | Toko Yakuhin Kogyo Kabushiki Kaisha | Rhinal spray nozzle used for medical syringe |
WO2023120535A1 (ja) * | 2021-12-20 | 2023-06-29 | 東興薬品工業株式会社 | ポリアクリル酸系ポリマーを含有するワクチンアジュバント剤およびその使用 |
US11826388B2 (en) | 2013-12-20 | 2023-11-28 | Seed Health, Inc. | Topical application of Lactobacillus crispatus to ameliorate barrier damage and inflammation |
US11833177B2 (en) | 2013-12-20 | 2023-12-05 | Seed Health, Inc. | Probiotic to enhance an individual's skin microbiome |
US11839632B2 (en) | 2013-12-20 | 2023-12-12 | Seed Health, Inc. | Topical application of CRISPR-modified bacteria to treat acne vulgaris |
US11844720B2 (en) | 2011-02-04 | 2023-12-19 | Seed Health, Inc. | Method and system to reduce the likelihood of dental caries and halitosis |
US11951140B2 (en) | 2011-02-04 | 2024-04-09 | Seed Health, Inc. | Modulation of an individual's gut microbiome to address osteoporosis and bone disease |
US11951139B2 (en) | 2015-11-30 | 2024-04-09 | Seed Health, Inc. | Method and system for reducing the likelihood of osteoporosis |
US11969445B2 (en) | 2013-12-20 | 2024-04-30 | Seed Health, Inc. | Probiotic composition and method for controlling excess weight, obesity, NAFLD and NASH |
US11980643B2 (en) | 2013-12-20 | 2024-05-14 | Seed Health, Inc. | Method and system to modify an individual's gut-brain axis to provide neurocognitive protection |
US11998574B2 (en) | 2013-12-20 | 2024-06-04 | Seed Health, Inc. | Method and system for modulating an individual's skin microbiome |
US11998479B2 (en) | 2011-02-04 | 2024-06-04 | Seed Health, Inc. | Method and system for addressing adverse effects on the oral microbiome and restoring gingival health caused by sodium lauryl sulphate exposure |
US12005085B2 (en) | 2013-12-20 | 2024-06-11 | Seed Health, Inc. | Probiotic method and composition for maintaining a healthy vaginal microbiome |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9603919B2 (en) * | 2009-03-31 | 2017-03-28 | Japan As Represented By The Director-General Of National Institute Of Infectious Diseases | Method for prophylaxis of influenza using vaccine for intranasal administration |
CN105342982B (zh) * | 2015-11-19 | 2018-08-28 | 上海现代药物制剂工程研究中心有限公司 | 经鼻给药的流感疫苗免疫制剂及其制备方法 |
WO2017090766A1 (ja) * | 2015-11-27 | 2017-06-01 | 日東電工株式会社 | 口腔内投与用ワクチン医薬組成物及び口腔内投与用ワクチン医薬組成物の製造方法 |
KR101944953B1 (ko) * | 2016-07-29 | 2019-02-01 | 메타볼랩(주) | 점막용 항인플루엔자 바이러스 조성물 |
CN113117093B (zh) * | 2019-12-31 | 2024-02-09 | 辽宁成大生物股份有限公司 | 一种适用于鼻粘膜递送流感疫苗的促进剂 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0338529A (ja) * | 1989-07-04 | 1991-02-19 | Toko Yakuhin Kogyo Kk | 鼻腔内噴霧投与用インフルエンザワクチンゲル製剤 |
WO2007123207A1 (ja) | 2006-04-21 | 2007-11-01 | Toko Yakuhin Kogyo Kabushiki Kaisha | 流体用容器およびこれを用いたエアレス式流体投与システム |
WO2007123193A1 (ja) | 2006-04-21 | 2007-11-01 | Toko Yakuhin Kogyo Kabushiki Kaisha | スプレー用ゲルタイプ皮膚・粘膜付着型製剤およびそれを用いた投与システム |
WO2010114169A1 (en) | 2009-03-31 | 2010-10-07 | Japan As Represented By The Director-General Of National Institute Of Infectious Diseases | Method for prophylaxis of influenza using vaccine for intranasal administration |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5215739A (en) * | 1989-04-05 | 1993-06-01 | Toko Yakuhin Kogyo Kabushiki Kaisha | Spray gel base and spray gel preparation using thereof |
US5158761A (en) * | 1989-04-05 | 1992-10-27 | Toko Yakuhin Kogyo Kabushiki Kaisha | Spray gel base and spray gel preparation using thereof |
JP5869744B2 (ja) * | 2005-03-23 | 2016-02-24 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | Cd4t細胞および/または改善された記憶b細胞応答を誘導するためのインフルエンザウイルスおよび水中油型エマルジョンアジュバントの使用 |
-
2013
- 2013-10-23 EP EP19167809.3A patent/EP3566715A1/en not_active Withdrawn
- 2013-10-23 ES ES13867863T patent/ES2731899T3/es active Active
- 2013-10-23 PT PT13867863T patent/PT2939692T/pt unknown
- 2013-10-23 LT LTEP13867863.6T patent/LT2939692T/lt unknown
- 2013-10-23 KR KR1020157016766A patent/KR102071099B1/ko active IP Right Grant
- 2013-10-23 US US14/653,131 patent/US20160015800A1/en not_active Abandoned
- 2013-10-23 PL PL13867863T patent/PL2939692T3/pl unknown
- 2013-10-23 EP EP13867863.6A patent/EP2939692B1/en active Active
- 2013-10-23 SI SI201331485T patent/SI2939692T1/sl unknown
- 2013-10-23 RU RU2015130634A patent/RU2652296C2/ru active
- 2013-10-23 SG SG10201705190TA patent/SG10201705190TA/en unknown
- 2013-10-23 DK DK13867863.6T patent/DK2939692T3/da active
- 2013-10-23 HU HUE13867863 patent/HUE044434T2/hu unknown
- 2013-10-23 SG SG11201504648TA patent/SG11201504648TA/en unknown
- 2013-10-23 MX MX2015008380A patent/MX371154B/es active IP Right Grant
- 2013-10-23 NZ NZ70892213A patent/NZ708922A/en unknown
- 2013-10-23 MY MYPI2015701959A patent/MY173503A/en unknown
- 2013-10-23 CN CN201380068031.4A patent/CN104884086A/zh active Pending
- 2013-10-23 CN CN201910188181.8A patent/CN110038123A/zh active Pending
- 2013-10-23 AU AU2013367751A patent/AU2013367751B2/en active Active
- 2013-10-23 WO PCT/JP2013/078721 patent/WO2014103488A1/ja active Application Filing
- 2013-10-23 BR BR112015015523-5A patent/BR112015015523B1/pt active IP Right Grant
- 2013-10-23 JP JP2014554202A patent/JP6247639B2/ja active Active
- 2013-10-23 CA CA2894223A patent/CA2894223C/en active Active
- 2013-10-23 TR TR2019/10293T patent/TR201910293T4/tr unknown
- 2013-10-30 TW TW102139274A patent/TWI624280B/zh active
-
2015
- 2015-06-08 IL IL239284A patent/IL239284B/en active IP Right Grant
- 2015-06-26 PH PH12015501482A patent/PH12015501482B1/en unknown
- 2015-10-28 HK HK15110594.2A patent/HK1209646A1/xx unknown
-
2018
- 2018-11-26 US US16/200,233 patent/US20190091324A1/en not_active Abandoned
-
2019
- 2019-06-28 CY CY20191100681T patent/CY1122372T1/el unknown
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0338529A (ja) * | 1989-07-04 | 1991-02-19 | Toko Yakuhin Kogyo Kk | 鼻腔内噴霧投与用インフルエンザワクチンゲル製剤 |
WO2007123207A1 (ja) | 2006-04-21 | 2007-11-01 | Toko Yakuhin Kogyo Kabushiki Kaisha | 流体用容器およびこれを用いたエアレス式流体投与システム |
WO2007123193A1 (ja) | 2006-04-21 | 2007-11-01 | Toko Yakuhin Kogyo Kabushiki Kaisha | スプレー用ゲルタイプ皮膚・粘膜付着型製剤およびそれを用いた投与システム |
WO2010114169A1 (en) | 2009-03-31 | 2010-10-07 | Japan As Represented By The Director-General Of National Institute Of Infectious Diseases | Method for prophylaxis of influenza using vaccine for intranasal administration |
Non-Patent Citations (2)
Title |
---|
OKA T. ET AL.: "Influenza vaccine: enhancement of immune response by application of carboxy-vinylpolymer.", VACCINE, vol. 8, no. 6, 1990, pages 573 - 576, XP026927094 * |
See also references of EP2939692A4 |
Cited By (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9750802B2 (en) | 2009-11-18 | 2017-09-05 | Katherine Rose Kovarik | Method and system for targeting the microbiome to promote health and treat allergic and inflammatory diseases |
US9457077B2 (en) | 2009-11-18 | 2016-10-04 | Katherine Rose Kovarik | Method and system for targeting the microbiome to promote health and treat allergic and inflammatory diseases |
US10716815B2 (en) | 2011-02-04 | 2020-07-21 | Katherine Rose Kovarik | Method and system for treating cancer and other age-related diseases by extending the healthspan of a human |
US9730967B2 (en) | 2011-02-04 | 2017-08-15 | Katherine Rose Kovarik | Method and system for treating cancer cachexia |
US9585920B2 (en) | 2011-02-04 | 2017-03-07 | Katherine Rose Kovarik | Method and system for treating cancer cachexia |
US11844720B2 (en) | 2011-02-04 | 2023-12-19 | Seed Health, Inc. | Method and system to reduce the likelihood of dental caries and halitosis |
US11998479B2 (en) | 2011-02-04 | 2024-06-04 | Seed Health, Inc. | Method and system for addressing adverse effects on the oral microbiome and restoring gingival health caused by sodium lauryl sulphate exposure |
US10314865B2 (en) | 2011-02-04 | 2019-06-11 | Katherine Rose Kovarik | Method and system for treating cancer and other age-related diseases by extending the healthspan of a human |
US11951140B2 (en) | 2011-02-04 | 2024-04-09 | Seed Health, Inc. | Modulation of an individual's gut microbiome to address osteoporosis and bone disease |
US11998574B2 (en) | 2013-12-20 | 2024-06-04 | Seed Health, Inc. | Method and system for modulating an individual's skin microbiome |
US11980643B2 (en) | 2013-12-20 | 2024-05-14 | Seed Health, Inc. | Method and system to modify an individual's gut-brain axis to provide neurocognitive protection |
US11969445B2 (en) | 2013-12-20 | 2024-04-30 | Seed Health, Inc. | Probiotic composition and method for controlling excess weight, obesity, NAFLD and NASH |
US9408880B2 (en) | 2013-12-20 | 2016-08-09 | Katherine Rose Kovarik | Method and system for prevention and treatment of allergic and inflammatory diseases |
US11839632B2 (en) | 2013-12-20 | 2023-12-12 | Seed Health, Inc. | Topical application of CRISPR-modified bacteria to treat acne vulgaris |
US12005085B2 (en) | 2013-12-20 | 2024-06-11 | Seed Health, Inc. | Probiotic method and composition for maintaining a healthy vaginal microbiome |
US11826388B2 (en) | 2013-12-20 | 2023-11-28 | Seed Health, Inc. | Topical application of Lactobacillus crispatus to ameliorate barrier damage and inflammation |
US11833177B2 (en) | 2013-12-20 | 2023-12-05 | Seed Health, Inc. | Probiotic to enhance an individual's skin microbiome |
US11103453B2 (en) | 2014-06-25 | 2021-08-31 | Toko Yakuhin Kogyo Kabushiki Kaisha | Rhinovaccination system of influenza vaccine |
US11020346B2 (en) | 2014-06-25 | 2021-06-01 | Toko Yakuhin Kogyo Kabushiki Kaisha | Rhinal spray nozzle used for medical syringe |
EP3162378A4 (en) * | 2014-06-25 | 2018-01-17 | Toko Yakuhin Kogyo Kabushiki Kaisha | Influenza vaccine nasal vaccination system |
US11951139B2 (en) | 2015-11-30 | 2024-04-09 | Seed Health, Inc. | Method and system for reducing the likelihood of osteoporosis |
US11491219B2 (en) | 2017-10-05 | 2022-11-08 | Tokyo Yakuhin Kogyo Co., Ltd. | Nasal hepatitis B vaccine composition and method for producing same |
JPWO2019070019A1 (ja) * | 2017-10-05 | 2020-10-22 | 東興薬品工業株式会社 | 経鼻b型肝炎ワクチン組成物およびその製造方法 |
WO2019070019A1 (ja) * | 2017-10-05 | 2019-04-11 | 東興薬品工業株式会社 | 経鼻b型肝炎ワクチン組成物およびその製造方法 |
WO2021002355A1 (ja) | 2019-07-03 | 2021-01-07 | アイリス株式会社 | インフルエンザウイルス感染症を治療するための医薬組成物 |
WO2023120535A1 (ja) * | 2021-12-20 | 2023-06-29 | 東興薬品工業株式会社 | ポリアクリル酸系ポリマーを含有するワクチンアジュバント剤およびその使用 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6247639B2 (ja) | 経鼻インフルエンザワクチン組成物 | |
TWI721949B (zh) | 流行性感冒疫苗經鼻接種系統 | |
JP2023012539A (ja) | 経鼻b型肝炎ワクチン組成物およびその製造方法 | |
EP4026559A1 (en) | Seasonal influenza vaccine capable of inducing virus-specific antibody into nasal cavity | |
RU2773357C2 (ru) | Назальная вакцинная композиция против гепатита b и способ ее получения |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 13867863 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 2894223 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 239284 Country of ref document: IL |
|
ENP | Entry into the national phase |
Ref document number: 2014554202 Country of ref document: JP Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 14653131 Country of ref document: US |
|
ENP | Entry into the national phase |
Ref document number: 20157016766 Country of ref document: KR Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: MX/A/2015/008380 Country of ref document: MX |
|
WWE | Wipo information: entry into national phase |
Ref document number: IDP00201503969 Country of ref document: ID Ref document number: 12015501482 Country of ref document: PH |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
REG | Reference to national code |
Ref country code: BR Ref legal event code: B01A Ref document number: 112015015523 Country of ref document: BR |
|
ENP | Entry into the national phase |
Ref document number: 2013367751 Country of ref document: AU Date of ref document: 20131023 Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2013867863 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref document number: 2015130634 Country of ref document: RU Kind code of ref document: A |
|
ENP | Entry into the national phase |
Ref document number: 112015015523 Country of ref document: BR Kind code of ref document: A2 Effective date: 20150626 |