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ES2362525B8 - Formulación de medicamentos en forma de agujas percutaneas penetrantes. - Google Patents

Formulación de medicamentos en forma de agujas percutaneas penetrantes. Download PDF

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Publication number
ES2362525B8
ES2362525B8 ES200930820A ES200930820A ES2362525B8 ES 2362525 B8 ES2362525 B8 ES 2362525B8 ES 200930820 A ES200930820 A ES 200930820A ES 200930820 A ES200930820 A ES 200930820A ES 2362525 B8 ES2362525 B8 ES 2362525B8
Authority
ES
Spain
Prior art keywords
needles
hardness
drug
stiffness
medication
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.)
Expired - Fee Related
Application number
ES200930820A
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English (en)
Other versions
ES2362525B1 (es
ES2362525A1 (es
Inventor
Arcadio Garcia De Castro Andrews
Raúl García Carrodeaguas
Niuris Acosta Contreras
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.)
Azurebio SL
Original Assignee
Azurebio SL
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
Priority to ES200930820A priority Critical patent/ES2362525B8/es
Application filed by Azurebio SL filed Critical Azurebio SL
Priority to CA2785315A priority patent/CA2785315A1/en
Priority to PCT/EP2010/065106 priority patent/WO2011042542A1/en
Priority to EP10771379A priority patent/EP2485711A1/en
Priority to US13/500,279 priority patent/US9271927B2/en
Priority to AU2010305368A priority patent/AU2010305368A1/en
Priority to CN2010800559557A priority patent/CN102647977A/zh
Priority to BR112012010443A priority patent/BR112012010443A2/pt
Priority to AP2012006260A priority patent/AP2012006260A0/xx
Publication of ES2362525A1 publication Critical patent/ES2362525A1/es
Publication of ES2362525B1 publication Critical patent/ES2362525B1/es
Application granted granted Critical
Publication of ES2362525B8 publication Critical patent/ES2362525B8/es
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
    • 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
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0021—Intradermal administration, e.g. through microneedle arrays, needleless injectors
    • 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
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A61K39/29—Hepatitis virus
    • A61K39/292—Serum hepatitis virus, hepatitis B virus, e.g. Australia antigen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0042—Photocleavage of drugs in vivo, e.g. cleavage of photolabile linkers in vivo by UV radiation for releasing the pharmacologically-active agent from the administered agent; photothrombosis or photoocclusion
    • 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
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0069—Devices for implanting pellets, e.g. markers or solid medicaments
    • 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
    • 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
    • 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
    • A61K2039/55561—CpG containing adjuvants; Oligonucleotide containing adjuvants
    • 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
    • A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
    • C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
    • C08F220/04—Acids; Metal salts or ammonium salts thereof
    • C08F220/06—Acrylic acid; Methacrylic acid; Metal salts or ammonium salts thereof
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
    • C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
    • C08F220/52—Amides or imides
    • C08F220/54—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide
    • C08F220/56—Acrylamide; Methacrylamide
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F222/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a carboxyl radical and containing at least one other carboxyl radical in the molecule; Salts, anhydrides, esters, amides, imides, or nitriles thereof
    • C08F222/10—Esters
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F222/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a carboxyl radical and containing at least one other carboxyl radical in the molecule; Salts, anhydrides, esters, amides, imides, or nitriles thereof
    • C08F222/10—Esters
    • C08F222/1006—Esters of polyhydric alcohols or polyhydric phenols
    • C08F222/102—Esters of polyhydric alcohols or polyhydric phenols of dialcohols, e.g. ethylene glycol di(meth)acrylate or 1,4-butanediol dimethacrylate
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F222/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a carboxyl radical and containing at least one other carboxyl radical in the molecule; Salts, anhydrides, esters, amides, imides, or nitriles thereof
    • C08F222/30—Nitriles
    • C08F222/32—Alpha-cyano-acrylic acid; Esters thereof
    • C08F222/321—Alpha-cyano-acrylic acid methyl ester
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F222/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a carboxyl radical and containing at least one other carboxyl radical in the molecule; Salts, anhydrides, esters, amides, imides, or nitriles thereof
    • C08F222/30—Nitriles
    • C08F222/32—Alpha-cyano-acrylic acid; Esters thereof
    • C08F222/322—Alpha-cyano-acrylic acid ethyl ester, e.g. ethyl-2-cyanoacrylate
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F222/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a carboxyl radical and containing at least one other carboxyl radical in the molecule; Salts, anhydrides, esters, amides, imides, or nitriles thereof
    • C08F222/30—Nitriles
    • C08F222/32—Alpha-cyano-acrylic acid; Esters thereof
    • C08F222/324—Alpha-cyano-acrylic acid butyl ester
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F222/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a carboxyl radical and containing at least one other carboxyl radical in the molecule; Salts, anhydrides, esters, amides, imides, or nitriles thereof
    • C08F222/30—Nitriles
    • C08F222/32—Alpha-cyano-acrylic acid; Esters thereof
    • C08F222/326—Alpha-cyano-acrylic acid longer chain ester
    • 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
    • C12N2730/00—Reverse transcribing DNA viruses
    • C12N2730/00011—Details
    • C12N2730/10011—Hepadnaviridae
    • C12N2730/10111—Orthohepadnavirus, e.g. hepatitis B virus
    • C12N2730/10134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Virology (AREA)
  • Dermatology (AREA)
  • Engineering & Computer Science (AREA)
  • Mycology (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Medical Informatics (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Anesthesiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Communicable Diseases (AREA)
  • Neurosurgery (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)

Abstract

La invención se refiere a formulaciones de medicamentos para su administración en forma de agujas percutáneas penetrantes sólidas, “agujas inyectables”, fabricadas mediante procesos de polimerización por adición. El proceso de polimerización implica la transformación de una fase líquida que contiene monómeros en un cuerpo sólido monolítico, que contiene el medicamento, con la forma, dureza y rigidez requeridas para ser inyectadas en el tejido subcutáneo mediante sencillos dispositivos empujadores o inyectores. Estos procedimientos permiten la incorporación directa del medicamento a las agujas inyectables, o su incorporación en nano- o micro-partículas preformuladas para preservar la integridad y acción terapéutica del medicamento que contienen, así como de agentes modificadores de la velocidad de degradación, perfil de liberación del medicamento, dureza y rigidez, o inmunogenicidad.
ES200930820A 2009-10-08 2009-10-08 Formulación de medicamentos en forma de agujas percutaneas penetrantes. Expired - Fee Related ES2362525B8 (es)

Priority Applications (9)

Application Number Priority Date Filing Date Title
ES200930820A ES2362525B8 (es) 2009-10-08 2009-10-08 Formulación de medicamentos en forma de agujas percutaneas penetrantes.
AP2012006260A AP2012006260A0 (en) 2009-10-08 2010-10-08 Formulation of drugs and vaccines in the form of percutaneous injectable needles.
EP10771379A EP2485711A1 (en) 2009-10-08 2010-10-08 Formulation of drugs and vaccines in the form of percutaneous injectable needles
US13/500,279 US9271927B2 (en) 2009-10-08 2010-10-08 Formulation of drugs and vaccines in the form of percutaneous injectable needles
AU2010305368A AU2010305368A1 (en) 2009-10-08 2010-10-08 Formulation of drugs and vaccines in the form of percutaneous injectable needles
CN2010800559557A CN102647977A (zh) 2009-10-08 2010-10-08 经皮注射针形式的药物和疫苗的配制剂
CA2785315A CA2785315A1 (en) 2009-10-08 2010-10-08 Formulation of drugs and vaccines in the form of percutaneous injectable needles
PCT/EP2010/065106 WO2011042542A1 (en) 2009-10-08 2010-10-08 Formulation of drugs and vaccines in the form of percutaneous injectable needles
BR112012010443A BR112012010443A2 (pt) 2009-10-08 2010-10-08 formulação de fármacos e vacinas na forma de agulhas injetáveis por via percutãnea

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
ES200930820A ES2362525B8 (es) 2009-10-08 2009-10-08 Formulación de medicamentos en forma de agujas percutaneas penetrantes.

Publications (3)

Publication Number Publication Date
ES2362525A1 ES2362525A1 (es) 2011-07-07
ES2362525B1 ES2362525B1 (es) 2012-06-07
ES2362525B8 true ES2362525B8 (es) 2013-01-03

Family

ID=43662245

Family Applications (1)

Application Number Title Priority Date Filing Date
ES200930820A Expired - Fee Related ES2362525B8 (es) 2009-10-08 2009-10-08 Formulación de medicamentos en forma de agujas percutaneas penetrantes.

Country Status (9)

Country Link
US (1) US9271927B2 (es)
EP (1) EP2485711A1 (es)
CN (1) CN102647977A (es)
AP (1) AP2012006260A0 (es)
AU (1) AU2010305368A1 (es)
BR (1) BR112012010443A2 (es)
CA (1) CA2785315A1 (es)
ES (1) ES2362525B8 (es)
WO (1) WO2011042542A1 (es)

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US9089677B2 (en) * 2011-01-25 2015-07-28 The Regents Of The University Of California Transcutaneous multimodal delivery system (TMDS)
WO2013059295A2 (en) * 2011-10-17 2013-04-25 Trustees Of Boston University Polymeric depots for localization of an agent to biological sites
GB2498774A (en) * 2012-01-27 2013-07-31 Bruce Roser Glass-stabilised biological materials and syringe
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CN103083659B (zh) * 2013-01-18 2015-05-13 北京华夏兴洋生物科技有限公司 新型无油佐剂制备方法及用途
CN104248760B (zh) * 2013-12-16 2021-07-23 普莱柯生物工程股份有限公司 一种疫苗组合物及其制备方法和应用
EP3193829B1 (en) * 2014-09-19 2021-12-08 Oxular Limited Ophthalmic drug compositions
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CN106177939B (zh) * 2015-06-01 2021-01-19 普莱柯生物工程股份有限公司 一种疫苗用佐剂及其应用
US10400105B2 (en) 2015-06-19 2019-09-03 The Research Foundation For The State University Of New York Extruded starch-lignin foams
CN106344920B (zh) * 2015-07-16 2020-11-27 普莱柯生物工程股份有限公司 一种疫苗用佐剂及其应用
EP3429663B1 (en) * 2016-03-15 2020-07-15 Amgen Inc. Reducing probability of glass breakage in drug delivery devices
CN106177944A (zh) * 2016-08-18 2016-12-07 山东滨州博莱威生物技术有限公司 一种用于鸡新城疫活疫苗的佐剂
CN106177942A (zh) * 2016-08-18 2016-12-07 山东滨州博莱威生物技术有限公司 一种用于仔猪副伤寒活疫苗佐剂
CN106466295A (zh) * 2016-10-17 2017-03-01 四川华神兽用生物制品有限公司 一种疫苗稀释液及其制备方法与应用
US11369677B2 (en) 2017-01-31 2022-06-28 Alf Lamprecht Use of nanoparticles for immunotherapy
CN107375921B (zh) * 2017-06-12 2019-10-29 商丘美兰生物工程有限公司 一种甘草皂苷脂质体免疫佐剂及其制备方法
JP6482604B2 (ja) * 2017-06-22 2019-03-13 教裕 南郷 外皮内溶解型ニードル及びニードル装置
GB2568579B (en) 2017-09-15 2022-06-29 Oxular Ltd Ophthalmic drug compositions
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CA2785315A1 (en) 2011-04-14
US9271927B2 (en) 2016-03-01
AP2012006260A0 (en) 2012-06-30
ES2362525B1 (es) 2012-06-07
WO2011042542A1 (en) 2011-04-14
CN102647977A (zh) 2012-08-22
US20120219589A1 (en) 2012-08-30
BR112012010443A2 (pt) 2019-01-08
ES2362525A1 (es) 2011-07-07
EP2485711A1 (en) 2012-08-15

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