WO1998041199A1 - Decongestionnant nasal ou oculaire - Google Patents

Decongestionnant nasal ou oculaire Download PDF

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Publication number
WO1998041199A1
WO1998041199A1 PCT/JP1998/000994 JP9800994W WO9841199A1 WO 1998041199 A1 WO1998041199 A1 WO 1998041199A1 JP 9800994 W JP9800994 W JP 9800994W WO 9841199 A1 WO9841199 A1 WO 9841199A1
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WO
WIPO (PCT)
Prior art keywords
compound
nasal
present
nose
administration
Prior art date
Application number
PCT/JP1998/000994
Other languages
English (en)
Japanese (ja)
Inventor
Hiromichi Tsuru
Yojiro Ukai
Original Assignee
Nippon Shinyaku 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 Nippon Shinyaku Co., Ltd. filed Critical Nippon Shinyaku Co., Ltd.
Priority to JP54033998A priority Critical patent/JP4096363B2/ja
Publication of WO1998041199A1 publication Critical patent/WO1998041199A1/fr

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Classifications

    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/18—Sulfonamides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents

Definitions

  • the present invention relates to a 3 ′-(2-amino-1- 1-hydroxyxethyl) -14,1-fluoromethanesulfonylanilide (hereinafter referred to as a compound) having a microvasoconstriction of the nose or eyes and having a small effect on blood pressure. (Referred to as (1)) as an active ingredient.
  • Nasal congestion is characteristic of diseases such as colds, allergic rhinitis, sinusitis or hay fever. Nasal congestion is caused by dilation of blood vessels in the nasal mucosa, resulting in swelling of the tissue covering the nasal cavity. The microvessels of the nasal mucosa are known to be rich in hy-adrenergic receptors. Eye hyperemia is also characteristic of allergic conjunctivitis. Eye hyperemia is caused by dilation of the conjunctival blood vessels.
  • L-adrenergic receptor agonists such as oxymetazoline, naphazoline, and amidefrin reduce congestion in nasal tissues by contracting microvessels in the nasal mucosa. These drugs also relieve eye redness.
  • ⁇ - ⁇ -adrenergic receptor agonists used for the treatment of nasal microvascular hyperemia are problematic in that they have strong central nervous system side effects such as insomnia and agitation, or strong cardiovascular side effects such as increased blood pressure, palpitations and arrhythmias. Had become.
  • An object of the present invention is to provide a remedy for nasal or ocular hyperemia, which has a nasal or ocular microvasoconstriction effect and has few or no side effects such as increased blood pressure.
  • Pharmaceutically acceptable salts of compound (1) include salts of mineral acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, and phosphoric acid, acetic acid, citric acid, tartaric acid, maleic acid, succinic acid, fumaric acid, p — Salts of organic acids such as toluenesulfonic acid, benzenesulfonic acid and methanesulfonic acid.
  • mineral acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, and phosphoric acid
  • acetic acid such as citric acid, tartaric acid, maleic acid, succinic acid, fumaric acid
  • p Salts of organic acids such as toluenesulfonic acid, benzenesulfonic acid and methanesulfonic acid.
  • the compound according to the present invention has an excellent nasal microvasoconstriction effect.
  • the present invention The compound according to the above has little effect on blood pressure and the like. This is a feature of the present invention.
  • the compound according to the present invention also has a conjunctival microvascular contraction effect, has little effect on blood pressure and the like, and is also useful as a therapeutic agent for ocular hyperemia.
  • the compound of the present invention when administered as a medicament, the compound of the present invention may be used as it is or in a pharmaceutically acceptable non-toxic and inert carrier, for example, 0.01 to 99.5%, preferably It is administered to animals including humans as a pharmaceutical composition containing 0.5 to 90%.
  • a pharmaceutically acceptable non-toxic and inert carrier for example, 0.01 to 99.5%, preferably It is administered to animals including humans as a pharmaceutical composition containing 0.5 to 90%.
  • the carrier of the pharmaceutical composition according to the present invention one or more solid, semi-solid or liquid diluents, fillers and other prescription auxiliaries are used.
  • the pharmaceutical compositions are administered in dosage unit form.
  • the pharmaceutical composition of the present invention can be administered orally, intravenously, transdermally, intranasally or by eye drops. Needless to say, it is administered in a dosage form suitable for these administration methods.
  • administration by a nebulizer or nasal drops or oral administration is particularly preferred.
  • ophthalmic administration or oral administration is particularly preferred.
  • the dose of the compound of the present invention as a therapeutic agent for nasal or ocular hyperemia is determined in consideration of the patient's condition such as age and weight, the administration route, the nature and extent of the disease, and the like.
  • the amount of the active ingredient of the compound of the present invention for an adult is generally in the range of 0.01 to 1000 mg / day, preferably in the range of 0.1 to 10 mg / day.
  • lower doses may be sufficient, and conversely, higher doses may be required. It can also be administered in divided doses two to three times a day.
  • solid or liquid dosage units such as powders, powders, tablets, dragees, capsules, granules, suspensions, solutions, emulsions, syrups, drops, sublingual tablets, etc. It can be performed with other dosage forms.
  • Intranasal administration can be carried out by nasal or spraying a solution, suspension, emulsion and the like.
  • suitable liquid media include pharmaceutically usable alcohols such as water and propylene glycol or pharmaceutically usable vegetable oils such as sesame oil or peanut oil.
  • Intranasal administration can also be carried out in ointments, gels or other forms. Dosage forms for nasal administration may be sterile and require Depending on the type, auxiliary agents such as preservatives, stabilizers, emulsifiers, tonicity agents or buffering agents may be contained.
  • Administration by eye drops can be carried out with a solution, suspension, emulsion or the like.
  • suitable liquid media include pharmaceutically usable alcohols such as water or propylene dalicol.
  • the dosage form for ophthalmic administration is generally sterile and may contain adjuvants such as preserving, stabilizing, emulsifying, isotonic or buffering agents as necessary. Good.
  • the pharmaceutical composition of the present invention may contain or combine other drugs, for example, other nasal or ocular hyperemia inhibitors.
  • Specimens are suspended in a tissue bath containing Krebs solution, aerated with 95% O 2 + 5% C02, maintained at 37 ° C, loaded with 0.5 g and flushed with Krebs solution every 15-20 minutes. Equilibrated for about 1 hour with replacement.
  • Nonolepinephrine 6 6.32 It is clear that the compound according to the present invention has a strong nasal mucosa microvasoconstriction action similar to that of norepinephrine.
  • test was performed using 3-6 male male egrets (body weight: 1.4-3.1 kg) per group under anesthesia by subcutaneous administration of urethane 1-1.2 g / kg under fasting conditions.
  • the required amount of the test drug (compound (1A), amidefrin) suspended in a 0.5% methylcellulose aqueous solution was administered into the duodenum at a volume of 0.5 ml / kg.
  • Changes in blood pressure were measured over time after administration. Blood pressure was measured using a blood pressure measuring force-Yure inserted into the femoral artery. Table 2 shows the results.
  • Amidefrin has a strong vasopressor effect at doses considered necessary for onset
  • the compound according to the present invention has almost no effect on blood pressure in an effective amount.
  • mice (ddy male, 6 to 8 weeks old) were used as 4 rats per group, and rats (SD male, 6 to 7 weeks old) were used as 6 rats per group.
  • the fasted animals were orally administered the required amounts of the test drugs (compound (1A) and amidefrin) in a volume of 10 ml / kg using an oral sonde. After administration of the drug, the animals were returned to a state where they could freely take food and water, and observed for general symptoms and deaths for 2 weeks.
  • the test drug was orally administered by suspending it in a physiological saline solution containing 0.5% methylcellulose. Table 3 shows the results.
  • the mixed powder in this ratio is tableted and made into an internal tablet.
  • the compound according to the present invention is useful as a therapeutic agent for nasal or ocular hyperemia.

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  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Pulmonology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Ophthalmology & Optometry (AREA)
  • Epidemiology (AREA)
  • Otolaryngology (AREA)
  • Medicinal Preparation (AREA)

Abstract

Cette composition de médicament contient en tant que principe actif, soit 3'-(2-amino-1-hydroxyéthyl)-4'-fluorométhanesulfonanilide, soit un isomère optique de celui-ci, ou un sel de ceux-ci, acceptable sur le plan pharmacologique. Ces composés possèdent un effet micro-vasoconstricteur sur le nez ou sur les yeux et sont efficaces pour remédier à la congestion du nez ou de l'oeil, sans exercer d'influence sur la pression sanguine.
PCT/JP1998/000994 1997-03-14 1998-03-10 Decongestionnant nasal ou oculaire WO1998041199A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP54033998A JP4096363B2 (ja) 1997-03-14 1998-03-10 鼻又は眼の充血治療剤

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP6032197 1997-03-14
JP9/60321 1997-03-14

Publications (1)

Publication Number Publication Date
WO1998041199A1 true WO1998041199A1 (fr) 1998-09-24

Family

ID=13138803

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1998/000994 WO1998041199A1 (fr) 1997-03-14 1998-03-10 Decongestionnant nasal ou oculaire

Country Status (2)

Country Link
JP (1) JP4096363B2 (fr)
WO (1) WO1998041199A1 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0173597A1 (fr) * 1984-07-13 1986-03-05 Henri Najer Nouveaux éther-oxydes dérivés de cyclopropylphénols
EP0230532A1 (fr) * 1985-12-11 1987-08-05 Abbott Laboratories 2-[(3,5-Dihalo-4-aminobenzyl)]imidazolines
JPH03128332A (ja) * 1989-07-12 1991-05-31 Eisai Co Ltd α↓１―ブロッカー点眼剤
JPH05271053A (ja) * 1992-03-27 1993-10-19 Lion Corp 安定な点眼剤

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0173597A1 (fr) * 1984-07-13 1986-03-05 Henri Najer Nouveaux éther-oxydes dérivés de cyclopropylphénols
EP0230532A1 (fr) * 1985-12-11 1987-08-05 Abbott Laboratories 2-[(3,5-Dihalo-4-aminobenzyl)]imidazolines
JPH03128332A (ja) * 1989-07-12 1991-05-31 Eisai Co Ltd α↓１―ブロッカー点眼剤
JPH05271053A (ja) * 1992-03-27 1993-10-19 Lion Corp 安定な点眼剤

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
TANIGUCHI N., ET AL.: "NS-49, AN ALPHA1A-ADRENOCEPTOR AGONIST, SELECTIVELY INCREASES INTRAURETHRAL PRESSURE IN DOGS.", EUROPEAN JOURNAL OF PHARMACOLOGY, ELSEVIER SCIENCE, NL, vol. 318., no. 01., 1 January 1996 (1996-01-01), NL, pages 117 - 122., XP002912522, ISSN: 0014-2999, DOI: 10.1016/S0014-2999(96)00766-2 *

Also Published As

Publication number Publication date
JP4096363B2 (ja) 2008-06-04

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