JP4300347B2 - Glaucoma treatment agent consisting of bunazosin and prostaglandins - Google Patents

Description

【００２８】
表１に示したように、ブナゾシンとラタノプロストの併用群ではブナゾシン投与群およびラタノプロスト投与群よりもさらに眼圧が下降した。上記のことから、ブナゾシンとプロスタグランジン類を組み合わせることにより、より強い眼圧下降を得られることが明らかとなった。
【００２９】
【発明の効果】
ブナゾシンとプロスタグランジン類とを組み合わせて投与すると、眼圧下降作用が増強された。よって本発明の医薬組成物は緑内障の治療剤として有用である。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a therapeutic agent for glaucoma comprising a combination of bunazosin or a salt thereof and prostaglandins.
[0002]
[Prior art]
Glaucoma is an intractable eye disease that increases the intraocular pressure due to various factors and can lead to blindness, and various treatment methods have been studied. There are three methods for lowering intraocular pressure: drug therapy, laser therapy, and surgery. Drug therapy includes drugs such as β-blockers, prostaglandin-related drugs, carbonic anhydrase inhibitors, cholinergic drugs, and epinephrine-related drugs.
[0003]
Recently, bunazosin hydrochloride, an α1 blocker, was developed as a drug based on a new mechanism of action. Bunazosin hydrochloride is a selective sympathetic α1 receptor blocker and lowers intraocular pressure by promoting aqueous humor outflow from the uveal sclera outflow tract (Japanese Journal of Ophthalmology 46,1066-1070, 1995).
[0004]
As a combination of an α1 blocker and another glaucoma therapeutic agent, JP-A 2001-33551 reports a glaucoma therapeutic agent by a combination of an α1 blocker and an angiotensin II antagonist.
[0005]
On the other hand, a combination of an adrenergic blocker and a prostaglandin is reported in Japanese Patent No. 2726672 as a glaucoma therapeutic agent by a combination of a prostaglandin and another agent. However, this report focuses on β-blockers as adrenergic blockers, and does not describe the effects of using α-blockers, and does not particularly suggest any effects on α1-blockers. .
[0006]
Thus, no glaucoma treatment effect has been reported by the combination of α1 blocker and prostaglandins so far, especially about the combination of bunazosin and prostaglandins which are α1 blockers having a novel mechanism of action. No research has been done at all.
[0007]
[Problems to be solved by the invention]
Thus, finding a usefulness as a therapeutic agent for glaucoma by a combination of bunazosin having a novel mechanism of action and prostaglandins has been a very interesting subject.
[0008]
[Means for solving problems]
As a result of intensive research on the possibility of development as a therapeutic agent for glaucoma by the combination of bunazosin and prostaglandins, the present inventors have found that combining these enhances the intraocular pressure lowering action, and the present invention has been completed. I let you. The detailed test method and the results will be described in the section of pharmacological test described later. The combination of bunazosin and prostaglandins showed a remarkable intraocular pressure lowering effect. Moreover, the glaucoma therapeutic agent by this invention can be used suitably not only for the treatment of glaucoma but also for prevention.
[0009]
DETAILED DESCRIPTION OF THE INVENTION
The present invention is a therapeutic agent for glaucoma comprising a combination of bunazosin or a salt thereof and latanoprost , which is one of prostaglandins, and complements and / or enhances the action of each other.
[0010]
Regarding the treatment of glaucoma, bunazosin and prostaglandins may be administered in the form of a single preparation, that is, administered as a combination, or they may be administered as separate preparations, that is, in the form of combined administration. Good.
[0011]
Bunazocin may be in the form of a salt, and examples of the salt include salts with inorganic acids such as hydrochloric acid and nitric acid, with hydrochloride being particularly preferred.
[0012]
The prostaglandins used in the present invention are latanoprost (see Japanese Patent Publication No. 3-501025). Latanoprost may be in the form of a salt or ester.
[0013]
The preparation for carrying out the present invention may be a preparation in which bunazosin and prostaglandins are blended, or may be a preparation in which each component is separated. No special technique is required for the preparation of these preparations, and preparations may be prepared using widely used techniques. The administration method is preferably topical ocular administration, and examples of the dosage form include eye drops and eye ointment.
[0014]
When preparing a preparation in which bunazosin and prostaglandins are separately prepared, they can be prepared according to known methods. For example, as a preparation of bunazosin, a preparation disclosed in Japanese Patent No. 2610619 and Japanese Patent Publication No. 7-23302 or a commercially available preparation can be used. Prostaglandin preparations can be formulated with reference to the description of the above-mentioned published patent publications. In particular, commercially available preparations may be used for latanoprost, isopropyl unoprostone, etc. that are already on the market as glaucoma treatment drugs. it can.
[0015]
When preparing a preparation in which bunazosin and prostaglandins are blended, it can be prepared according to a known method. In the case of eye drops, isotonic agents such as sodium chloride and concentrated glycerin, buffers such as sodium phosphate and sodium acetate, interfaces such as polyoxyethylene sorbitan monooleate, polyoxyl 40 stearate, polyoxyethylene hydrogenated castor oil An activator, a stabilizer such as sodium citrate and sodium edetate, and a preservative such as benzalkonium chloride and paraben can be used as necessary. The pH may be in the range acceptable for ophthalmic preparations, but is preferably in the range of 4-8. For reference, some of the formulation examples are described in the Examples section below, but the formulation examples do not limit the scope of the present invention.
[0016]
The dose of bunazosin and prostaglandins is determined according to the patient's symptoms, age, dosage form, route of administration, and the like. For example, in the case of ophthalmic administration, the dose of bunazosin is usually administered in the range of 2 to 40 μg per day, once a day or divided into several times. The dose of prostaglandins varies depending on the type of drug, but is determined on the basis of the dose in the range actually used for treatment, and may be appropriately increased or decreased depending on symptoms. The daily dose is in the range of 1-1000 μg, and is administered once or divided into several times. More specifically, in the case of isopropyl unoprostone, a daily dose of 30 to 300 μg is usually used, and in the case of latanoprost, a daily dose of 1 to 5 μg is usually used. Increase or decrease as appropriate. Other prostaglandins may be determined based on similar criteria. These doses are applied when bunazosin and prostaglandins are administered in combination. However, when bunazosin and prostaglandins are combined in a single preparation, the daily dose is applied. Is prepared in such a manner that the mixing ratio is appropriately selected so that the amount is less than or equal to the amount of each component described above, and the combined preparation is administered once or several times a day.
[0017]
In the following, formulation examples and pharmacological tests are shown as examples, but these examples are for better understanding of the present invention and do not limit the scope of the present invention.
[0018]
【Example】
[Formulation example]
A typical formulation example of an eye drop as a combination drug of bunazosin and prostaglandins in the present invention is shown below.
[0019]
Eye drops (in 100 mL)
0.01g bunazosin hydrochloride
Latanoprost 0.005g
Boric acid 0.5g
Concentrated glycerin 2.0g
Benzalkonium chloride 0.01g
Dilute hydrochloric acid Appropriate amount Purified water Appropriate amount [0020]
[Pharmacological test]
In order to investigate the usefulness of combined use of bunazosin and prostaglandins, cynomolgus monkeys were administered with bunazosin and prostaglandins in combination, and the effect on intraocular pressure was examined. Latanoprost was used for prostaglandins.
[0021]
(Test compound solution)
For administration of bunazosin, Detantol (registered trademark) ophthalmic solution (an ophthalmic solution containing 0.01% bunazosin hydrochloride) was used. Xalatan (registered trademark) ophthalmic solution (ophthalmic solution containing 0.005% latanoprost) was used for latanoprost administration.
[0022]
(Administration group)
Cynomolgus monkeys were divided into four administration groups: a base administration group, a bunazosin administration group, a latanoprost administration group, and a bunazosin + latanoprost administration group.
[0023]
(Administration method and measurement method)
1. One drop of 0.4% oxybuprocaine hydrochloride ophthalmic solution was instilled into one eye of a normal cynomolgus monkey, and the intraocular pressure before administration was measured after local anesthesia.
[0024]
2. The test compound solution was then instilled. In the base administration group, 20 μL of the base was instilled. In the bunazosin administration group, 20 μL of detantol ophthalmic solution was instilled. In the latanoprost administration group, 20 μL of xalatan ophthalmic solution was instilled. In the bunazosin + latanoprost administration group, 20 μL of detanthol ophthalmic solution was instilled, and after 5 minutes, 20 μL of xalatan ophthalmic solution was instilled.
[0025]
3. Two hours, 4 hours, and 6 hours after administration of the test compound solution, one drop of 0.4% oxybuprocaine hydrochloride ophthalmic solution was instilled, and the intraocular pressure was measured after local anesthesia. For each group, the maximum intraocular pressure drop value was determined from the following equation.
[0026]
Maximum intraocular pressure drop = (intraocular pressure at the time when the intraocular pressure dropped most)-(intraocular pressure before administration)
(Results and Discussion)
The experimental results are shown in Table 1.
[0027]
[Table 1]

[0028]
As shown in Table 1, the intraocular pressure further decreased in the combination group of bunazosin and latanoprost than in the bunazosin administration group and the latanoprost administration group. From the above, it was revealed that stronger intraocular pressure reduction can be obtained by combining bunazosin and prostaglandins.
[0029]
【The invention's effect】
When bunazosin and prostaglandins were administered in combination, the intraocular pressure lowering effect was enhanced. Therefore, the pharmaceutical composition of the present invention is useful as a therapeutic agent for glaucoma.

Claims (2)

A therapeutic agent for glaucoma consisting of a combination of bunazosin or a salt thereof and latanoprost , except when it contains an angiotensin II antagonist . Bunazosin or therapeutic agent for glaucoma comprising the combination of a salt thereof with latanoprost, except the case of containing bunazosin or glaucoma therapeutic agents other than the salt and latanoprost.