WO1999034776A1 - Compositions de gouttes nasales - Google Patents

Compositions de gouttes nasales Download PDF

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Publication number
WO1999034776A1
WO1999034776A1 PCT/JP1999/000030 JP9900030W WO9934776A1 WO 1999034776 A1 WO1999034776 A1 WO 1999034776A1 JP 9900030 W JP9900030 W JP 9900030W WO 9934776 A1 WO9934776 A1 WO 9934776A1
Authority
WO
WIPO (PCT)
Prior art keywords
nasal
buffer
sodium
nasal drop
hydrochloride
Prior art date
Application number
PCT/JP1999/000030
Other languages
English (en)
Japanese (ja)
Inventor
Katsuyoshi Aikawa
Harumi Uda
Naoko Mitsutake
Noriko Matsubayashi
Original Assignee
Taisho Pharmaceutical Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Taisho Pharmaceutical Co., Ltd. filed Critical Taisho Pharmaceutical Co., Ltd.
Priority to AU17848/99A priority Critical patent/AU1784899A/en
Publication of WO1999034776A1 publication Critical patent/WO1999034776A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • 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

Definitions

  • the present invention relates to a nasal drop composition, and in particular, (a) a buffer solution capable of regulating nasal mucus pH, and (b) at least one antihistamine or antiallergic agent and a vasoconstrictor, or (c) corti.
  • the present invention relates to a novel nasal drop composition containing costosteroids.
  • the inventors of the present invention have conducted intensive studies and, as a result, have noticed that the elution of antigen from pollen particles is generally higher on the algal side, and the pH in the nasal cavity is reduced to a weak acidity. Hold for a long time and administer at least one antihistamine or anti-allergic agent and a vasoconstrictor or corticosteroids to reduce nasal inflammation (sneezing, stuffiness, nasal congestion, etc.) for a long time The inventors have found that it can be suppressed and completed the present invention.
  • the present invention provides (a) a buffer having a pH of 3 to 6, (b) at least one antihistamine or antiallergic agent and a vasoconstrictor, or (c) corticosteroid.
  • the present invention relates to a nasal composition containing steroids.
  • the effect can be further maintained by including the cation-responsive polymer in the composition.
  • the nasal drop composition containing the cation-responsive polymer is liquid when sprayed, but responds to cations in the nasal mucus and nasal mucosa when it comes into contact with the nasal mucus and nasal mucosa, and forms a gel-like coating. Form.
  • This gel-like coating can keep the pH in the nasal cavity weakly acidic for a long time and can suppress the transfer of the allergen substance into the nasal mucosa.
  • the antihistamine and antiallergic agent used in the present invention are those commonly used in nasal drops and are not particularly limited, but may include iproheptene hydrochloride, chlorpheniramine maleate, diphenhydramine, diphenhydramine hydrochloride, isothihydrochloride.
  • An antihistamine such as pentyl, sodium cromoglycate, tranist, ketotifen fumarate, azelastine hydrochloride, oxatoside, terfenadine, an antiallergic agent such as ezmedastine fumarate, astemizole, or a combination thereof can be used. .
  • a combination of chlorfurinilamine maleate and ketotifen fumarate or chlorpheniramine maleate and astemizole is used.
  • the compounding amount is from 0.025 to 1.0% by weight based on the total amount of the nasal composition.
  • vasoconstrictor examples include epinephrine, ephedrine hydrochloride, naphazoline, naphazoline hydrochloride, tetrahydrozoline, tetrahydrozoline hydrochloride, tetrahydrozoline nitrate, fenirephrine hydrochloride, and d1-methylephedrine hydrochloride.
  • a preferred amount is from 0.025 to 0.1% by weight based on the total amount of the nasal composition.
  • corticosteroids examples include hydrocortisone butyrate propionate, hydrocortisone acetate, hydrocortisone, prednisolone, beclomethasone propionate, flumethasone, dexamethasone, betamethasone, betamethasone valerate and the like.
  • the compounding amount is preferably from 0.01 to 0.3% by weight based on the total amount of the nasal composition.
  • the buffer solution of pH 3 to 6 used in the present invention has a pH adjusting ability to keep nasal mucus pH in the nasal mucosa in a weakly acidic region.
  • citrate-sodium citrate ⁇ Buffer D (+) sodium tartrate monohydroxide buffer, sodium citrate monohydroxide buffer, potassium hydrogen phthalate-HCl buffer, glycine monohydrochloride buffer, tran s-alconitine-hydroxyl Sodium buffer, formate-sodium formate buffer, lactic acid
  • the cation-responsive polymer that can be used in the present invention is a polymer that gels in response to cations in the nasal mucosa and nasal mucus, and includes, for example, dielan gum, pectin, and sodium alginate. Among them, diurane gum is particularly preferred. It is desirable that the nasal composition be incorporated in an amount of 0.01 to 2.0% by weight.
  • the nasal drop composition of the present invention includes, in addition to the above substances, substances commonly used in nasal drops, for example, anti-inflammatory agents (dipotassium dalityrrhizinate, methyl salicylate, acetoaminophen, acetylsalicylic acid, glycol salicylate, Indomethacin, etc.), Local anesthetics (Lidocaine, lidocaine hydrochloride, Jib forcein, Jibforcein hydrochloride, benzocaine, aminoethyl benzoate), fungicides (acrinol, cetylpyridinium chloride, chloride) Nzetoniu ⁇ , Benzarukoniumu chloride, chlorhexidine into hydrochloric chloro, chlorhexidine or the like to the grayed Rukon acid chlorine), vitamins (vitamin A, vitamin C, vitamin B 1 2, etc.), fresheners (menthol, camphor, eucalyptus oil, etc.) , Thickeners (gelatin, poly
  • the nasal drop composition of the present invention is prepared by adding various components to an aqueous phase and dissolving them, followed by final production. It can be prepared by adjusting the pH of the agent to 3 to 6. Alternatively, the compositions are sprayed on in the liquid form for administration to the nose by conventional means, such as a nasal drop.
  • FIG. 1 illustrates the pH measurement results of Test Example 2.
  • Example 1 ADVANTAGE OF THE INVENTION
  • Chlorpheniramine maleate 0.5 (% by weight)
  • 26-52 14-year-old pollen allergic rhinitis patients were divided into 2 groups, 7 in group A and 7 in group B, and the course of symptoms caused by nasal drops was observed for 2 weeks.
  • Example 1 was administered
  • Group B the nasal composition of Comparative Example was sprayed twice into both nasal passages before going out and at home.
  • the degree of allergic symptoms during the day was determined by self-report and recorded in the symptom progress chart.
  • Other rhinitis medications were discontinued during the study.
  • the nasal cavity of a rat having a tube inserted into the posterior nasal cavity from the esophagus was washed with physiological saline, and the sample 1001 of Example 4 was administered to one nasal cavity.
  • the nasal fluid collected by sending air from the esophagus at regular intervals was used to measure the pH using a pH sensor (pH2135: Nihon Kohden) and a PHZPC02 monitor (KR-5000: Nihon Kohden). It was measured.
  • the sample of Example 5 except that dielan gum and sodium polyphosphate were removed from the formulation of Example 4, the pH in the rat nasal cavity was measured in the same manner as above.
  • Example 4 As a result, as shown in FIG. 1, in Example 4, the pH in the nasal cavity was kept weakly acidic for a long time. Industrial applicability
  • a nasal drop composition which is excellent in hay fever and highly persistent.

Abstract

Compositions de gouttes nasales exerçant un effet puissant et prolongé sur l'hypersensibilité aux pollens et contenant (a) un tampon possédant une valeur de pH de 3 à 6 et (b) au moins un ingrédient sélectionné dans des agents antihistaminiques, des agents antiallergiques et un vasoconstricteur ou (c) des corticostéroïdes. On peut obtenir une action prolongée supplémentaire par apport à ces compositions de polymères sensibles aux cations.
PCT/JP1999/000030 1998-01-09 1999-01-08 Compositions de gouttes nasales WO1999034776A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU17848/99A AU1784899A (en) 1998-01-09 1999-01-08 Nasal drop compositions

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP10/2703 1998-01-09
JP270398 1998-01-09

Publications (1)

Publication Number Publication Date
WO1999034776A1 true WO1999034776A1 (fr) 1999-07-15

Family

ID=11536657

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1999/000030 WO1999034776A1 (fr) 1998-01-09 1999-01-08 Compositions de gouttes nasales

Country Status (2)

Country Link
AU (1) AU1784899A (fr)
WO (1) WO1999034776A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007123193A1 (fr) * 2006-04-21 2007-11-01 Toko Yakuhin Kogyo Kabushiki Kaisha Préparation en gel vaporisable pour adhésion à la peau ou aux muqueuses et système d'administration utilisant la préparation
JP2008120795A (ja) * 2006-10-18 2008-05-29 Taisho Pharmaceutical Co Ltd 粘膜適用液剤
US8136703B2 (en) 2006-04-21 2012-03-20 Toko Yakuhin Kogyo Kabushiki Kaisha Fluid container and airless fluid dispensing system

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS50129723A (fr) * 1974-03-30 1975-10-14
JPS62292719A (ja) * 1986-06-12 1987-12-19 Kaken Pharmaceut Co Ltd 外用澄明水溶性製剤
JPH04279531A (ja) * 1991-03-06 1992-10-05 Kazuhiko Tsuchikura 点鼻薬
JPH07109218A (ja) * 1993-08-18 1995-04-25 Terumo Corp アミド誘導体含有水性液剤
JPH07258070A (ja) * 1994-03-23 1995-10-09 Taisho Pharmaceut Co Ltd 鼻洗浄剤
JPH07258069A (ja) * 1994-03-16 1995-10-09 Taisho Pharmaceut Co Ltd 持効性点鼻剤

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS50129723A (fr) * 1974-03-30 1975-10-14
JPS62292719A (ja) * 1986-06-12 1987-12-19 Kaken Pharmaceut Co Ltd 外用澄明水溶性製剤
JPH04279531A (ja) * 1991-03-06 1992-10-05 Kazuhiko Tsuchikura 点鼻薬
JPH07109218A (ja) * 1993-08-18 1995-04-25 Terumo Corp アミド誘導体含有水性液剤
JPH07258069A (ja) * 1994-03-16 1995-10-09 Taisho Pharmaceut Co Ltd 持効性点鼻剤
JPH07258070A (ja) * 1994-03-23 1995-10-09 Taisho Pharmaceut Co Ltd 鼻洗浄剤

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007123193A1 (fr) * 2006-04-21 2007-11-01 Toko Yakuhin Kogyo Kabushiki Kaisha Préparation en gel vaporisable pour adhésion à la peau ou aux muqueuses et système d'administration utilisant la préparation
US8136703B2 (en) 2006-04-21 2012-03-20 Toko Yakuhin Kogyo Kabushiki Kaisha Fluid container and airless fluid dispensing system
AU2007241815B2 (en) * 2006-04-21 2012-08-16 Toko Yakuhin Kogyo Kabushiki Kaisha Sprayable gel-type skin/mucosa-adhesive preparation and administration system using the preparation
JP5185109B2 (ja) * 2006-04-21 2013-04-17 東興薬品工業株式会社 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
US8771711B2 (en) 2006-04-21 2014-07-08 Toko Yakuhin Kogyo Kabushiki Kaisha Sprayable gel-type skin/mucosa-adhesive preparation and administration system using the preparation
CN104940943A (zh) * 2006-04-21 2015-09-30 东兴药品工业株式会社 喷雾用凝胶型皮肤·粘膜附着型制剂及使用它的给药系统
CN104940943B (zh) * 2006-04-21 2019-01-04 东兴药品工业株式会社 喷雾用凝胶型皮肤·粘膜附着型制剂及使用它的给药系统
JP2008120795A (ja) * 2006-10-18 2008-05-29 Taisho Pharmaceutical Co Ltd 粘膜適用液剤

Also Published As

Publication number Publication date
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