Therapeutic agent for meibomian dysfunction

a meibomian gland and therapeutic agent technology, applied in the field of meibomian gland dysfunction, can solve the problems of lowering the quality of life of many patients, not knowing the effective treatment method of mgd, and not being clear for those skilled in the ar

Inactive Publication Date: 2018-01-25
SANTEN PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0047]The compound of the above-mentioned formula (1) or a pharmaceutically acceptable salt thereof is useful as a prophylactic and / or therapeutic agent for meibomian gland dysfunction (MGD).BEST MODE TO CARRY OUT THE INVENTION
[0048](A) The present compound is a compound in which the respective groups are the groups shown below in the compound represented by the formula (1):
[0049](A1) R1 represents a hydroxyl group, a methoxy group, a hydroxymethoxy group, an ethoxy group, a 1-hydroxyethoxy group, a 2-hydroxyethoxy group, a 2-methoxyethoxy group, a 2-ethoxyethoxy group, a formyloxy group, a carboxyoxy group, an acetoxy group, a hydroxyacetoxy group, a propionyloxy group, a 2-hydroxypropionyloxy group, a 3-hydroxypropionyloxy group, a 2-methylpropionyloxy group, a 2-(hydroxymethyl)propionyloxy group, a 3-hydroxy-2-(hydroxymethyl)propionyloxy group, a 2,2-dimethylpropionyloxy group, a 2-(hydroxymethyl)-2-methylpropionyloxy group, a 2,2-bis(hydroxymethyl)propionyloxy group, a methylphosphynoyloxy group, a dimethylphosphynoyloxy group or a 1H-tetrazol-1-yl group;
[0050](A2) R2 represents a hydrogen atom, a hydroxyl group, a methoxy group, a mercapto group, a methylthio group, a phenyl group, a 2,4,6-trihydroxyphenyl group or a 2,4,6-trimethoxyphenyl group; and
[0051](A3) R3 represents a hydrogen atom, a hydroxyl group or a methoxy group.

Problems solved by technology

In Non-Patent Document 1, it has been disclosed that among the patients visiting ophthalmology who appeal symptoms such as ocular discomfort, as a main complaint, meibomian gland dysfunction (hereinafter also referred to as “MGD”) becomes a cause thereof in a significant proportion, and lowering in quality of life is caused in many patients.
However, it has never been known an effective treatment method of MGD, and yet, clear definition for MGD or diagnostic criteria itself has never been present in the first place.
However, in Patent Document 1, it has never been disclosed whether the mTOR inhibitor has a treatment effect on MGD or not.
In addition, it is also not clear for those skilled in the art whether or not a medicament which can treat dry eye or posterior blepharitis can prevent and / or treat MGD itself.

Method used

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  • Therapeutic agent for meibomian dysfunction
  • Therapeutic agent for meibomian dysfunction
  • Therapeutic agent for meibomian dysfunction

Examples

Experimental program
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Effect test

examples

[0102][Test Using Complete Freund's Adjuvant Administered Rabbit]

[0103]In a complete Freund's adjuvant administered rabbit, telangiectasia around the meibomian gland orifices, and obstruction at the meibomian gland orifices, which are similar to the signs / findings of MGD can be recognized. Effects of sirolimus which was a representative example of the present compound on the telangiectasia and obstruction were investigated (see JP 2014-024835A).

[0104](Sample Preparation)

[0105]0.1% (w / v) sirolimus suspension: it was prepared by suspending in 0.01% (w / v) hydroxypropylmethyl cellulose. Incidentally, with regard to sirolimus, that purchased from LKT Laboratories, Inc., (Catalog number: R0161) was used (which is the same in the following Examples).

[0106](Test Method)

[0107]10 μL of the complete Freund's adjuvant was administered to the right upper eyelid (3 portions) of about 2 kg of male Japanese white rabbits, respectively. After 4 days from provocation, around the meibomian gland orifi...

preparation examples

[0126]The drugs of the present invention are more specifically explained by referring to Preparation examples, but the present invention is not limited by these Preparation examples alone.

Prescription example 1: Eye drop (0.1% (w / v))In 100 ml Sirolimus  0.1 gMedium chain fatty acid triglyceride (MCT) 7.5 gBenzalkonium chloride  0.2 gTyloxapol  1.2 gPoloxamer 188   1 gGlycerin 22.5 gSterile purified water q. s.

[0127]To sterile purified water are added sirolimus and the above-mentioned components other than these, and the mixture is thoroughly mixed to prepare an eye drop. Characteristics of the present eye drop is an emulsion. By changing the formulation amount of the sirolimus, eye drops with the concentration of the sirolimus of 0.05% (w / v), 0.5% (w / v) or 1% (w / v) can be prepared.

Prescription example 2: Eye drop (0.1% (w / v))In 100 ml Deforolimus  0.1 gMedium chain fatty acid triglyceride (MCT)  7.5 gBenzalkonium chloride  0.2 gTyloxapol  1.2 gPoloxamer 188   1 gGlycerin 22.5 gSteri...

prescription example 3

Ophthalmic Ointment or Ointment (Excluding Ophthalmic Ointment) (1% (w / w))

[0129]

In 100 g Sirolimus 1 g Liquid paraffin q.s. White petrolatum q.s.

[0130]Sirolimus is added to uniformly melt white petrolatum and liquid paraffin, and the mixture is thoroughly mixed and then gradually cooled to prepare an ophthalmic ointment or an ointment (excluding an ophthalmic ointment). By changing the formulation amount of the sirolimus, an ophthalmic ointment or an ointment (excluding an ophthalmic ointment) with the concentration of the sirolimus of 0.05% (w / w), 0.1% (w / w) or 0.5% (w / w) can be prepared.

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Abstract

A method for treatment of meibomian gland dysfunction in a mammalian subject, the method involving administering to the mammalian subject an eye drop comprising 0.01 to 0.5% (w / v) of sirolimus or a pharmaceutically acceptable salt thereof as a sole active ingredient, wherein the eye drop is administered to the eyes of the mammalian subject 1 to 2 times per day.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a divisional of U.S. application Ser. No. 14 / 775,019, filed Sep. 11, 2015, which is a U.S. national stage application of PCT / JP2014 / 056416, filed Mar. 12, 2014, which claims priority to Japanese Patent Application No. 2013-050766, filed Mar. 13, 2013, the contents of all of which are hereby incorporated by reference.TECHNICAL FIELD[0002]The present invention relates to a prophylactic and / or therapeutic agent for meibomian gland dysfunction containing a compound represented by the formula (1):wherein[0003]R1 represents a hydroxyl group, a methoxy group, a hydroxymethoxy group, an ethoxy group, a 1-hydroxyethoxy group, a 2-hydroxyethoxy group, a 2-methoxyethoxy group, a 2-ethoxyethoxy group, a formyloxy group, a carboxyoxy group, an acetoxy group, a hydroxyacetoxy group, a propionyloxy group, a 2-hydroxypropionyloxy group, a 3-hydroxypropionyloxy group, a 2-methylpropionyloxy group, a 2-(hydroxymethyl)-propionyloxy group...

Claims

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Application Information

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Patent Type & AuthorityApplications(United States)
IPC IPC(8): A61K31/436A61K9/00A61K31/675
CPCA61K31/675A61K31/436A61K9/0048A61P27/02A61P27/04A61P9/00A61P9/14A61P9/06A61K31/453A61K9/10A61K9/107
InventorMIYAKE, HIDEKIODA, TOMOKOSHII, DAISUKE
OwnerSANTEN PHARMA CO LTD