WO2015056710A1 - Préparation immune transdermique - Google Patents

Préparation immune transdermique Download PDF

Info

Publication number
WO2015056710A1
WO2015056710A1 PCT/JP2014/077432 JP2014077432W WO2015056710A1 WO 2015056710 A1 WO2015056710 A1 WO 2015056710A1 JP 2014077432 W JP2014077432 W JP 2014077432W WO 2015056710 A1 WO2015056710 A1 WO 2015056710A1
Authority
WO
WIPO (PCT)
Prior art keywords
antigen
base
transdermal
allergen
weight
Prior art date
Application number
PCT/JP2014/077432
Other languages
English (en)
Japanese (ja)
Inventor
英淑 権
文男 神山
中川　晋作
直貴 岡田
祥子 廣部
Original Assignee
コスメディ製薬株式会社
国立大学法人大阪大学
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by コスメディ製薬株式会社, 国立大学法人大阪大学 filed Critical コスメディ製薬株式会社
Publication of WO2015056710A1 publication Critical patent/WO2015056710A1/fr

Links

Images

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
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7084—Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
    • 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
    • A61K39/35—Allergens
    • 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
    • A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
    • A61K2039/541—Mucosal route
    • 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

Definitions

  • the present invention relates to a transdermal immunization preparation useful for transcutaneous immunization for regulating immune response.
  • immunotherapy by allergen administration is performed with the goal of complete cure.
  • the administration route is mainly subcutaneous injection, sublingual or oral, but it has not been established as a therapeutic method from the viewpoint of effectiveness and safety.
  • oral immunotherapy there are problems with its safety, and both rapid and slow methods have induced symptoms during or during the allergen load increase, and the incidence of adverse events is high, prompting patients to be prepared and determined
  • it can be said that it is a treatment method that exceeds the safety standards required for medical treatment at present.
  • effectiveness there are many cases in which the allergen load cannot be increased to the target value, and the patient repeats provoking symptoms during that time. Since it is necessary to reduce the load not only during the increase period but also during the maintenance period, it is currently impossible to overcome by improving the increase method.
  • transcutaneous immunotherapy using the immune system of the skin is not yet a general treatment for allergic diseases, but systemic symptoms are compared to conventional subcutaneous injection, sublingual and oral immunotherapy. Since the risk of induction is low, it is expected as a relatively safe and simple method.
  • a formulation for transcutaneous immunization comprising: wherein at least one of the components is dry, whereby application of the formulation to intact skin induces an antigen-specific immune response and Manufacturing a dry formulation for transcutaneous immunization, comprising: (a) providing at least one immunoactive component, wherein the formulation comprises at least one immunoactive component having antigenic activity; b) dissolving at least one of the immunoactive ingredients to create an immunoactive liquid; (c) drying the immunoactive liquid on a solid substrate such as a bandage; and (d) combining the immunoactive ingredients together Manufacturing process
  • Patent Document 2 is proposed, including in any order, wherein at least one of the immunologically active ingredients is dry, at least until the formulation is applied to the skin of the subject to be immunized
  • the skin covering our bodies is always exposed to the danger of pathogen invasion from the outside world.
  • the living body forms a first-line defense mechanism by providing a physical barrier called a stratum corneum and an immune barrier centering on Langerhans cells existing in the epidermis layer. Therefore, if a sufficient amount of antigen protein can be delivered to the epidermis layer through the stratum corneum, the antigen protein is captured by Langerhans cells, the control tower of the immune system, and an antigen-specific immune response can be efficiently induced. Conceivable.
  • the permeability of the stratum corneum to biopolymers such as proteins is extremely poor, and the antigenic protein cannot be delivered to the epidermis layer simply by applying a solution preparation to the skin.
  • the problem to be solved by the present invention is to provide a patch preparation that permeates the stratum corneum and sends the antigen protein to the epidermis layer, that is, a transdermal immunization preparation, by a simple technique.
  • the transdermal immunization preparation of the present invention comprises a base composed of an adhesive hydrophilic gel and an antigen laminated on the surface of the base, and regulates the immune response by application to intact skin.
  • modulate means both positive regulation, that is, regulatory induction that activates and promotes the immune system, and negative regulation, that is, regulation that suppresses the immune system.
  • the present invention intends to adapt the hydrophilic gel patch that we have developed so far as a device for an effective transdermal vaccine preparation for preventing infection, that is, a “paste vaccine preparation”, to transdermal immunotherapy for allergic diseases. It is.
  • Transdermal immunizations are thought to deliver antigens to cells of the immune system and induce immune responses without the aid of adjuvants.
  • the antigen passes through the normal protective outer layer of the skin (eg, the stratum corneum) and presents antigen-presenting cells (eg, macrophages, dendritic cells, skin dendritic cells, directly or directly to T lymphocytes, The immune response is induced through B lymphocytes or Kupffer cells).
  • the antigen may pass through the stratum corneum via hair follicles or skin organelles (eg, sweat glands, sebaceous glands).
  • an antigen means a substance that induces a specific immune response when presented to immune cells of an organism.
  • An antigen may comprise a single immunogenic epitope or multiple immunogenic epitopes recognized by a B cell receptor (ie, an antibody on the membrane of a B cell) or a T cell receptor.
  • the antigen a pathogen-derived antigen capable of infecting an organism selected from the group consisting of bacteria, viruses, fungi, and parasites, a pathogen-derived that can infect cells (for example, tumor cells or normal cells) Antigens.
  • the antigen include a tumor-related antigen or a self antigen.
  • examples of the antigen include allergens such as pollen, animal dander, mold, dust mite, flea antigen, salivary allergen, grass, food (for example, peanuts and other nuts), and Betv1.
  • the antigen may be a food allergen such as a milk allergen or an egg allergen.
  • the antigen may be a carbohydrate, glycolipid, glycoprotein, lipid, lipoprotein, phospholipid, polypeptide or a chemical or recombinant conjugate thereof.
  • Antigens are obtained by recombinant means, chemical synthesis or purification from natural sources, preferably proteinaceous antigens or conjugates with polysaccharides.
  • the antigen may be at least partially purified cell-free.
  • the antigen may be provided in the form of a live virus, an attenuated live virus, or an inactivated virus.
  • the antigen may be a nucleic acid (eg, DNA, RNA, cDNA, cRNA) encoding the antigen as appropriate.
  • the molecular weight of the antigen When the molecular weight of the antigen is 1,000 daltons or less, it tends to be absorbed inside when dropped in a solution state on a base made of a hydrophilic polymer substance, and the antigen may not be sufficiently concentrated on the surface of the base. As such, the molecular weight of the antigen is preferably greater than 1000 daltons.
  • the base is composed of an adhesive hydrophilic gel composed of a hydrophilic polymer substance that swells by absorbing water and / or water-containing alcohol. Since the antigen is dissolved or suspended in water and / or hydrous alcohol, dropping the aqueous solution or suspension onto a base composed of a hydrophilic polymer substance that absorbs and swells water and / or hydrous alcohol increases the hydrophilicity. Since the molecular substance absorbs water and / or hydrous alcohol, a concentrated antigen layer is laminated on the base surface.
  • hydrophilic polymer substance examples include polyalkyl alkoxy acrylate polymer substances, starch-acrylic acid graft polymer substances, polyacrylate polymer substances, polyvinyl alcohol polymer substances, and vinyl acetate- Examples thereof include acrylate polymer materials, polyvinyl pyrrolidone polymer materials, isobutylene-maleic acid polymer materials, N-vinylacetamide polymer materials, and the like.
  • the hydrophilic polymer substance When the hydrophilic polymer substance is cross-linked, it is preferable that the polymer substance has no or no decrease in strength even if it swells due to absorption of water and / or water-containing alcohol.
  • the crosslinking method any conventionally known method may be employed.
  • a metal complex such as a known polyfunctional isocyanate or aluminum acetylacetonate may be added as a crosslinking agent to the hydrophilic polymer substance.
  • the base is a hydrophilic polymer substance, 100 parts by weight of a copolymer comprising 40 to 60% by weight of methoxyethyl acrylate, 30 to 40% by weight of lauryl (meth) acrylate, and 10 to 25% by weight of a polar monomer. More preferably, it is composed of 30 to 50 parts by weight of octyldodecyl lactate, 20 to 50 parts by weight of glycerin, and 0.1 to 0.5 part of hyaluronic acid.
  • Examples of the polar monomer include N-vinyl-2-pyrrolidone, (meth) acrylic acid, 2-hydroxyethyl acrylate and the like.
  • methoxyethyl acrylate in the copolymer is increased, gelation is likely to occur during the polymerization and insolubility tends to occur, and the tackiness of the obtained pressure-sensitive adhesive tends to decrease.
  • content of lauryl (meth) acrylate decreases, the adhesiveness of the obtained adhesive tends to decrease.
  • the content of the polar monomer is decreased, the cohesive force of the obtained adhesive tends to be reduced, and when the content is increased, the adhesive suitable for sticking to the skin tends not to be obtained.
  • the ratio of methoxyethyl, lauryl (meth) acrylate and polar monomer is preferably within the above range.
  • Lactic acid octyldodecyl, glycerin and hyaluronic acid have the effect of further improving the hydrophilicity of the hydrophilic polymer substance and increasing the water absorbability and improving the adhesiveness to the skin and improving the skin adhesiveness, If the amount is small, the effect may be small. If the amount is large, the hydrophilic polymer substance becomes too soft and the practicality may be lowered, so the above range is preferable.
  • the hydrophilic gel may be composed of hyaluronic acid, glycerin, cosmol 13 and an acrylic pressure-sensitive adhesive. Their weight ratio is preferably 0.02: 3: 4.5: 10 in this order.
  • acrylic adhesive HiPAS10 (trade name) manufactured by Kosmedy Pharmaceutical Co., Ltd. can be used.
  • the transdermal immunity preparation of the present invention has an antigen layer laminated on the surface of the base, but the thickness of the base is not particularly limited, but if it is too thin, the antigen water and / or aqueous alcohol solution or suspension water And / or may not be able to absorb water-containing alcohol sufficiently, and if it is too thick, flexibility may be lost and contact with the skin may be reduced, so 20 to 5000 ⁇ m is preferable, and 50 to 2000 ⁇ m is more preferable. .
  • the shape of the base is not particularly limited, but is preferably a patch.
  • a support film such as a release sheet, a polyethylene film, a polypropylene film, a polyethylene terephthalate film, or a urethane film may be laminated on the surface of the base and the antigen layer.
  • the base preferably contains a plasticizer that is compatible with the hydrophilic polymer substance in order to improve the absorbability of water and / or hydrous alcohol.
  • the plasticizer may be hydrophilic and is preferably a liquid plasticizer. Examples thereof include glycerin, ethylene glycol, polyethylene glycol, dodecyl octyl lactate, sorbitan monooleate, sorbitan monopalmitate, and polyoxyethylene sorbitan monooleate.
  • the base preferably contains a chemical absorption enhancer in order to promote percutaneous absorption of the antigen.
  • a chemical absorption enhancer any conventionally known chemical absorption enhancer can be used.
  • alcohols such as menthol, camphor, and cetyl alcohol
  • fatty acid esters such as isopropyl palmitate and isopropyl myristate
  • monolaurin examples thereof include glycerin esters such as glycerin acid and glyceryl monooleate; acid amides such as lauric acid diethanolamide; neutral surfactants such as polyethylene glycol dilauryl ether. If the amount of the chemical transdermal absorption enhancer is too small, the percutaneous absorption effect will not be improved, and if it is too large, the adhesiveness of the base will be lowered. Is preferred.
  • protease examples include pepsin, trypsin, chymotrypsin, papain, collagenase, elastase, endoproteinase, pronase and the like, and examples thereof include pepsin, trypsin, chymotrypsin, papain and collagenase.
  • protease examples include pepsin, trypsin, chymotrypsin, papain and collagenase.
  • Lipase can be extracted and purified from animal pancreas, but a commercially available product may be used.
  • the transdermal immunization preparation of the present invention does not need to contain adjuvant, but the antigen layer or base may contain adjuvant.
  • An adjuvant is a substance that helps induce an immune response to an antigen, and a substance may act as both an adjuvant and an antigen by inducing an immune stimulus and a specific antibody or T cell response.
  • a transdermal immunological preparation is prepared by dropping an aqueous solution or suspension in which an antigen is dissolved or suspended in water and / or hydrous alcohol onto the surface of the base, and absorbing the water and / or hydrous alcohol into the base. Can be manufactured. Antigen is concentrated on the base surface to form an antigen layer.
  • water, alcohol containing water, alcohol such as ethanol, or a buffer solution thereof can be preferably used.
  • the buffer include Ca ++ / Mg ++ phosphate-free buffered saline (PBS), normal saline (150 mM NaCl aqueous solution), Tris buffer, and the like.
  • the antigen is generally solubilized with 10 mM acetic acid if the antigen is not dissolved in water or hydrous alcohol and its buffer, and then diluted to a desired volume with neutral water, hydroalcohol and buffer.
  • an antigen that dissolves only at acidic pH may be solubilized with dilute acetic acid, and then diluted with acetic acid-PBS as a diluent at acidic pH.
  • Hydrophobic antigens that are insoluble in themselves eg, hepatitis A virus, polypeptides containing domains across the membrane, etc.
  • the obtained aqueous solution or suspension is dropped on the surface of the base, and water or hydrous alcohol is absorbed into the base.
  • the base is composed of a hydrophilic polymer substance that absorbs and / or swells water and / or water-containing alcohol, water and / or water-containing alcohol in an aqueous solution or suspension can easily be used as a base (hydrophilic polymer substance). Absorbed, the antigen is left behind on the surface of the base (hydrophilic polymer substance) and a concentrated antigen layer is formed.
  • the enzyme treatment method is not particularly limited, and examples thereof include a method in which an enzyme aqueous solution in which an enzyme is dissolved in purified water adjusted to an appropriate pH is applied to the skin site. In that case, it is practically convenient to apply the enzyme aqueous solution soaked in filter paper or other porous simple substance.
  • Examples of different enzyme treatment methods include a method in which an enzyme ointment in which an enzyme is dissolved in an ointment base is applied to the skin, and a method in which an aqueous gel containing an enzyme dissolved in an aqueous gel is applied to the skin.
  • the current allergen immunotherapy mainly involves subcutaneous injection, sublingual administration or oral administration of allergen, but has the problems described in the problem column to be solved by the invention. Furthermore, allergen administration by injection is not only painful, but also has problems of side effects such as swelling and fever at the local site of administration. In contrast, transdermal allergen immunotherapy using hydrophilic gel patches may be superior in terms of safety and efficacy compared to conventional methods, and is said to be easy to administer and low cost. It can be a therapy that has advantages and can achieve improved patient quality of life. Further, the present invention is not limited to the treatment of food allergies, and is expected to be applicable to the development of new treatment methods for other allergic diseases as well as autoimmune diseases.
  • a transdermal immunization preparation having a concentrated antigen layer can be easily produced, and the transdermal immunization method of the present invention can prevent and treat the balance of the immune system without causing skin irritation. It can be changed in an advantageous manner. According to the configuration of the transdermal immunization preparation of the present invention, the immunological activity is high even without an adjuvant.
  • FIG. 1 is a diagram of the results of transdermal allergen immunotherapy.
  • FIG. 2 is a schematic front view of a transdermal immune preparation according to an embodiment of the present invention.
  • FIG. 2 is a schematic front view of a transdermally absorbable preparation according to one embodiment of the present invention.
  • the transdermally absorbable preparation 1 includes a base 2 and an antigen 3 laminated on the surface of the base 2.
  • the transdermal immunization preparation of the present invention is characterized by regulating the immune response by application to intact skin.
  • As a base it is comprised by the hydrophilic gel which has adhesiveness.
  • this antigen-specific antibody production is equivalent to the administration by injection for the production of IgE that leads to worsening of allergy (see FIG. 1), at least allergen may enter the blood and cause anaphylactic shock It is expected that it can be applied more safely than conventional subcutaneous injection methods.
  • the present invention uses an independently developed hydrophilic gel patch to deliver allergens transcutaneously into the living body, allowing Langerhans cells present in the epidermis layer to capture and recognize allergens, thereby improving the efficiency of antigen-specific immune responses. It is often evoked and tries to gain resistance to allergens. Langerhans cells are antigen-presenting cells that function as a control tower of the immune system, capture pathogens that have entered the living body from the skin, move to nearby lymph nodes, and transmit antigen information to immune effector cells. In order to perform percutaneous allergen immunotherapy targeting the intrinsic immunological function of the Langerhans cells, the allergen must break through the stratum corneum, which is the physical barrier of the outermost skin layer. It allows delivery to the skin tissue below the stratum corneum by keeping the local concentration of the allergen high.
  • Example 1 (Optimization of base composition)
  • five bases having the following composition and mixing weight ratio were prepared.
  • Base 1: Hyaluronic acid: Glycerin: Cosmol 13: HiPAS10 0.02: 3: 4.5: 10.
  • Base 2: Hyaluronic acid: Glycerin: Cosmol 13: HiPAS10 0.002: 0.4: 0.4: 10.
  • Base 4 DT2287 (National Starch Medical Adhesive).
  • Base 5 MASCOS 10 (Cosmed Pharmaceutical's medical adhesive). All of these bases have appropriate tackiness.
  • HiPAS10 (manufactured by Cosmed Pharmaceutical) is a hydrophilic acrylic adhesive, has excellent drug retention properties, can be oil-gelled, and is a suitable base for acidic and neutral drugs.
  • HiPAS10 was prepared by using azobisisobutyronitrile as a catalyst in ethyl acetate, 43.9% by weight of methoxyethyl acrylate, 36.7% by weight of lauryl acrylate, 6.1% by weight of vinylpyrrolidone, and 3.1% by weight of acrylic acid. And 10.2% by weight of hydroxyethyl acrylate are mixed and polymerized.
  • Base 1 Water droplet spread due to surface wetting and became 2.3 cm in diameter.
  • Base 3 which did not spread and had a diameter of 0.7 cm: The water droplet slightly shrunk and the diameter was 0.6 cm.
  • Base 4 and Base 5 Water droplets shrunk and the diameter was 0.5 cm or less.
  • HiPAS10 is a hydrophilic pressure-sensitive adhesive, and since hydrophilic substances such as glycerin and cosmol 13 are dissolved in a large amount, the affinity with water is remarkably high.
  • the affinity with water is high, when the antigen aqueous solution is dropped on the surface, moisture is quickly absorbed into the base and the antigen is held on the base surface. That is, the antigen is concentrated and stabilized, and when applied to the skin, the antigen can be smoothly transferred to the skin. Therefore, it can be concluded that Base 1 is optimal.
  • Example 2 A transdermal allergen immunotherapy preparation for food allergy was developed.
  • OVA immunity The OVA solution prepared with PBS was absorbed at 100 ⁇ g / 10 ⁇ l into the base 1 patch (1 ⁇ 2 cm 2 ), and the patch surface was dried at room temperature. The thus-prepared OVA-containing patch was affixed to the mouse auricle skin three times at intervals of 2 hours for 24 hours. In addition, 100 ⁇ g of OVA was immunized intradermally into mouse auricle skin at 2-week intervals three times, and this was used as a control group.
  • the plate was washed three times with TTBS, and HRP-conjugated goat-anti-mouse IgG (5000-fold dilution), IgG1 (5000-fold dilution), and IgG2a (2000-fold dilution) were added at 50 ⁇ l / well. After reacting at room temperature for 2 hours, it was washed 3 times with TTBS, and an HRP substrate solution was added at 100 ⁇ l / well. After 15 minutes, 2N H 2 SO 4 was added at 100 ⁇ l / well to stop the reaction, and the absorbance at an absorption wavelength of 450 nm and a sub wavelength of 655 nm was measured.
  • the maximum dilution ratio which is 0.1 or more higher than that of non-immunized mice, was expressed as Reciprocal log 2 titer.
  • the sample and antibody were diluted with Block Ace diluted 10 times with TTBS.
  • the production amount of the OVA-specific IgE antibody was measured using a Mouse anti-OVA IgE ELISA kit.
  • the measurement results are shown in FIG.
  • the hydrophilic gel patch method of the present invention shows an effect that is not significantly different from the conventional injection method.
  • Example 3 Stability evaluation of milk protein patch
  • the milk protein-coated surface was covered with a polyethylene terephthalate release film and sealed in an aluminum bag by heat sealing. Milk protein was quantified by storing at 4 ° C. and sampling periodically.
  • Quantitative method The milk protein patch was immersed in PBS (phosphate buffer) and shaken at 34 ° C. and 200 rpm for 1 hour to extract milk protein. Protein quantification of the extracted solution was performed by the Raleigh method. result: The milk protein content did not decrease during the storage period even at 6 months, confirming the stability in the patch.
  • Quantitative method At 3, 4, and 5 weeks, blood was collected from the mouse and serum was separated, and the IgG antibody titer of each serum was quantified by ELISA. result: When IgG antibody titers were measured at 3 weeks, 4 weeks and 5 weeks, the IgG antibody titers were 9 (3 weeks), 11 (4 weeks) and 14 (5 weeks). The antibody titer was high enough to be put to practical use. In addition, the unit of IgG antibody titer is Reciprocal log2 titer.

Abstract

　L'invention concerne une préparation immune transdermique utile pour une immunisation transdermique. La préparation immune transdermique (1) de la présente invention est caractérisée par le fait qu'elle comprend une base (2) et un antigène (3) superposé sur la surface de la base (2), la préparation immune transdermique (1) réglant la réponse immunitaire par application sur une peau intacte. Un antigène typique est un allergène. La base (2) est un gel hydrophile ayant des propriétés adhésives. En particulier, le gel hydrophile constituant la base (2) est configuré à partir d'acide hyaluronique, de glycérine, de Cosmol 13 et d'HiPAS10, le rapport de poids de ces constituants dans l'ordre énoncé étant de manière optimale 0,02:3:4,5:10.
PCT/JP2014/077432 2013-10-16 2014-10-15 Préparation immune transdermique WO2015056710A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2013227544A JP2016210684A (ja) 2013-10-16 2013-10-16 親水性ゲルパッチを用いた経皮アレルゲン免疫療法
JP2013-227544 2013-10-16

Publications (1)

Publication Number Publication Date
WO2015056710A1 true WO2015056710A1 (fr) 2015-04-23

Family

ID=52828152

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2014/077432 WO2015056710A1 (fr) 2013-10-16 2014-10-15 Préparation immune transdermique

Country Status (2)

Country Link
JP (1) JP2016210684A (fr)
WO (1) WO2015056710A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP6592791B1 (ja) * 2018-01-29 2019-10-23 株式会社リタファーマ 医薬製剤及びその製造方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008105504A1 (fr) * 2007-03-01 2008-09-04 Cosmed Pharmaceutical Co., Ltd. Préparation immunitaire transdermique, son procédé de fabrication et procédé d'immunisation transdermique à l'aide de la préparation
WO2008108209A1 (fr) * 2007-03-01 2008-09-12 Cosmed Pharmaceutical Co., Ltd. Préparation absorbable par voie percutanée et son procédé de production et procédé d'absorption percutanée
JP2013185151A (ja) * 2012-03-08 2013-09-19 Kosumedei Seiyaku Kk ひまし油配合テープ

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008105504A1 (fr) * 2007-03-01 2008-09-04 Cosmed Pharmaceutical Co., Ltd. Préparation immunitaire transdermique, son procédé de fabrication et procédé d'immunisation transdermique à l'aide de la préparation
WO2008108209A1 (fr) * 2007-03-01 2008-09-12 Cosmed Pharmaceutical Co., Ltd. Préparation absorbable par voie percutanée et son procédé de production et procédé d'absorption percutanée
JP2013185151A (ja) * 2012-03-08 2013-09-19 Kosumedei Seiyaku Kk ひまし油配合テープ

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
"Octyldodecyl Lactate", NIPPON HAN'YO KESHOHIN GENRYOSHU, 1997, pages 543 *
HIROBE S ET AL.: "Clinical study of transcutaneous vaccination using a hydrogel patch for tetanus and diphtheria.", VACCINE, vol. 30, no. 10, 2012, pages 1847 - 54, XP028462233, DOI: doi:10.1016/j.vaccine.2011.12.130 *
ISHII Y ET AL.: "A transcutaneous vaccination system using a hydrogel patch for viral and bacterial infection.", J CONTROL RELEASE., vol. 131, no. 2, 2008, pages 113 - 20, XP025478797, DOI: doi:10.1016/j.jconrel.2008.07.025 *
MATSUO K ET AL.: "Analysis of transcutaneous antigenic protein delivery by a hydrogel patch formulation.", J PHARM SCI., vol. 102, no. 6, 12 April 2013 (2013-04-12), pages 1936 - 47 *
MATSUO K ET AL.: "Transcutaneous vaccination using a hydrogel patch induces effective immune responses to tetanus and diphtheria toxoid in hairless rat.", J CONTROL RELEASE., vol. 149, no. 1, 2011, pages 15 - 20, XP027593308, DOI: doi:10.1016/j.jconrel.2010.05.012 *

Also Published As

Publication number Publication date
JP2016210684A (ja) 2016-12-15

Similar Documents

Publication Publication Date Title
AU2018200963B2 (en) Methods for effectively and rapidly desensitizing allergic patients
AU2002252378B2 (en) Transcutaneous immunostimulation
ES2372592T3 (es) Formulación seca para la inmunización transcutánea.
JP4875799B2 (ja) Ａｄｐ−リボシル化外毒素により誘引される経皮免疫応答を促進するための皮膚浸透性エンハンサーおよびバリア崩壊剤の使用
US20090136480A1 (en) Transcutaneous immunostimulation
JP2009516718A (ja) 経皮アレルゲン投与によるアレルギー治療
US20040137004A1 (en) Patch for transcutaneous immunization
JP2008505685A (ja) 経皮免疫処置用送達システム
JP2004525921A (ja) 経皮免疫用パッチ
EP2679242B1 (fr) Adjuvant pour l'administration transdermique ou transmuqueuse et préparation pharmaceutique le contenant
US20100047327A1 (en) Adjuvant for Transdermal or Transmucosal Administration and Pharmaceutical Preparation Containing the Same
JP2010059201A (ja) 経皮的免疫のアジュバント
WO2015056710A1 (fr) Préparation immune transdermique
JP5186678B2 (ja) 経皮抗原投与のための抗原キット
JPWO2008105504A1 (ja) 経皮免疫製剤、その製造方法及びそれを用いた経皮免疫方法
TWI642443B (zh) Adjuvant composition, adjuvant preparation containing the same, and kit
Bowersock et al. Vaccine Delivery Systems
JP2010059140A (ja) 経皮免疫製剤及びその製造方法
WO2014044690A1 (fr) Vaccins améliorés
JP2010284176A (ja) 製剤、当該製剤を用いたワクチンの投与方法及びイオントフォレーシス装置

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: 14854475

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 14854475

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: JP