JP2009040727A - Stable eye lotion containing latanoprost as active ingredient - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an eye lotion containing latanoprost (prostaglandin F2α derivative) and having improved stability with time. <P>SOLUTION: The latanoprost-containing eye lotion comprises polysorbate 80 as a nonionic surfactant. The content of polysorbate 80 is preferably 0.01-0.5%(W/V). The eye lotion may further comprise sodium dihydrogen phosphate, sodium hydrogen phosphate, etc., as a pH regulator, sodium chloride, etc., as an isotonicizing agent, and benzalkonium chloride, etc., as an antiseptic agent. The eye lotion is effective for glaucoma and ocular hypertension. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a stable ophthalmic solution containing latanoprost as an active ingredient.

  Latanoprost is a prostaglandin F2α derivative, and an ophthalmic solution containing latanoprost as an active ingredient is marketed for glaucoma and ocular hypertension.

  The above eye drops are known to produce several types of related substances in the stability test, and improvement in stability during storage is desired.

  For example, Patent Document 1 can store an ophthalmic solution containing latanoprost at room temperature by at least one means selected from means for adjusting pH to 5.0 to 6.25 and means for adding ε-aminocaproic acid. It is disclosed to stabilize to an extent.

JP 2004-182719 A

  However, the disclosed technique has a need for improvement, and development of a latanoprost ophthalmic solution having further excellent stability is beneficial.

  As a result of trial and error in order to solve the above-mentioned problems, the present inventors have completed the present invention by finding a novel fact that the addition of polysorbate 80 suppresses a decrease in content over time and improves stability.

  The polysorbate 80 used in the present invention is not particularly limited as long as it is a pharmaceutically acceptable amount, but is 0.001 to 0.5% (W / V), preferably 0.01 to 0% with respect to the total amount of the ophthalmic solution. It is 0.1% (W / V), particularly preferably 0.05% (W / V).

  Any other additive may be used as long as it is usually usable for eye drops, and examples thereof include buffers, isotonic agents, preservatives, and pH adjusters.

  For example, sodium citrate, sodium carbonate, boric acid, borax as buffer, sodium chloride, potassium chloride as isotonic agent, benzalkonium chloride, benzethonium chloride, sorbic acid, pH adjuster as preservative Examples include, but are not limited to, hydrochloric acid, sodium hydroxide, sodium dihydrogen phosphate, sodium hydrogen phosphate hydrate, and the like.

  When preparing an ophthalmic solution containing latanoprost as an active ingredient, the stability over time can be improved by adding polysorbate 80.

  The invention is illustrated by the following examples without however being limited in any way.

  In purified water, 170 mg of sodium dihydrogen phosphate, 360 mg of sodium hydrogen phosphate hydrate, 700 mg of sodium chloride, 100 μL of benzalkonium chloride solution and 0.05% (W / V) polysorbate 80 with respect to the total amount of eye drops Dissolve. This solution was added to a container in which 5 mg of latanoprost was previously weighed and charged, and after sufficient stirring until the compound was completely dissolved, the pH was adjusted and purified water was added to make up a total volume of 100 mL. The solution filtered through a filter was filled in a polyethylene container to give an eye drop solution.

Comparative example

  An ophthalmic solution was prepared by the same production method as in the examples without using polysorbate 80.

Stability test

  Table 1 shows the residual ratio (%) of latanoprost when the eye drops prepared in Examples and Comparative Examples were stored at 40 ° C. for 2 weeks and 4 weeks, and at 60 ° C. for 1 week and 2 weeks.

  As shown in Table 1, in the case of storage at 40 ° C. for 2 weeks, the comparative example in which polysorbate 80 was not added had a larger decrease in the residual rate than in the case of addition, and in the case of storage for 4 weeks, the change was slight in the examples. On the other hand, in the comparative example, a significant decrease in the residual rate was observed. In addition, at 60 ° C., the residual rate of the comparative example was larger than that of the example for both storage for 1 week and storage for 2 weeks. In particular, a significant difference was observed between the example and the comparative example when stored for 2 weeks.

  From the above results, in the production of ophthalmic solutions containing lacnoprost as an active ingredient, the addition of polysorbate 80 suppressed the decrease in the remaining rate during storage, and the improvement in stability over time was recognized.

Claims (2)

  An ophthalmic solution having improved stability over time, comprising polysorbate 80 in an ophthalmic solution containing latanoprost as an active ingredient.   The ophthalmic solution according to claim 1, wherein the content of the polysorbate 80 is 0.01 to 0.5% (W / V).