Pharmaceutical compositions and their use as mydriatics

Details Pharmaceutical compositions and their use as mydriatics Pharmaceutical compositions and their use as mydriatics

1986-08-26

1988-08-16

Robinson, Douglas W.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Ester doai

514912, A61K 31225

Patent

active

047645300

DESCRIPTION:

BRIEF SUMMARY
This invention relates to new pharmaceutical compositions and their use in ophthalmology.
More particularly this invention relates to new pharmaceutical compositions comprising ibopamine or a pharmaceutically acceptable addition salt thereof, and to their use as mydriatics.
Ibopamine (epinine 3,4-O-diisobutyrate) is a drug useful for systemic use in cardiovascular therapy (U.S. Pat. No. 4,218,470).
Now it has been found that ibopamine administered locally shows a considerable mydriatic effect and thus has different ophthalmological applications both in diagnosis, for examination of the fundus and refraction, and in ophthalmic surgery when it is desired to antagonize intraoperative myosis.
Although the use of sympathomimetic amines as mydriatics is conceptually a potentially beneficial alternative to the use of anticholinergic agents the only sympathomimetic agent finding limited use as a mydriatic is phenylephrine.
Phenylephrine has a moderate action and is not free of drawbacks because of systemic effects shown at the high concentrations (from 10 to 36%) which must be used to obtain the desired effect. Also the other available sympathomimetic drugs, particularly adrenaline are not free from drawbacks concerning local tolerability and the risk of systemic effects.
Suprisingly ibopamine has proven to be well suited as a mydriatic agent.
Ibopamine exhibits a strong mydriatic effect which is associated to an excellent pharmacodynamic profile characterized by rapid onset and subsequent rapid exhaustion of the effect with considerable benefit for the patient.
Along with this favourable profile of effectiveness it shows a very good local tolerability and absence of systemic side effects.
With respect to the atropine-like compounds which are the drugs most commonly used as mydriatics ibopamine has the advantage of producing a rapid onset of the effect which lasts just for a period of time consistent with the needs of the ophthalmological examination and is more rapidly exhausted. This behaviour is very favourable in ophthalmic diagnosis allowing rapid recovery of normal visual functions of the patient.
The mydriatic effect of the compounds was evaluated on male New Zealand rabbits weighing 2.5-3 kg in accordance with the following method.
The animals were placed in retention cages in a room lit with artificial light.
The diameter of the pupil was measured with a gauge (to 1/10 mm) and with the aid of a magnifying glass (1.5 diameters).
The compounds were dissolved in physiological solution and instilled in a 0.1 ml volume in the conjunctival sac of one eye while the contra-lateral eye was treated with an equal volume of physiological solution.
In the control animals physiological solution was instilled in both eyes.
The mydriatic effect of ibopamine was tested in comparison with adrenaline, adrenaline diisobutyrate and dipivalate, epinine and epinine dipivalate (U.S. Pat. No. 4,218,470 mentioned above) (Table 1).
Local tolerability and systemic effects in the rabbit, more particularly pressor effects (Table 1) were also investigated.


TABLE 1 ______________________________________ Effect on the rabbit after conjuctival instillation. Tolerability (conjunctival irritation and Blood Concen- relative pressure tration concentration variation.sup.3 Substance [mM].sup.1 [mM].sup.2) (mmHg) ______________________________________ Epinine HCl 100 -(100) -7 Epinine 3,4-O--diiso- 6.2 -(100) -7 butyrate hydrochloride Epinine 3,4-O--dipivalate 6.2 +(50) not tested hydrochloride dl-Adrenaline HCl 6.2 -(50) +48 dl-Adrenaline 3,4-O--di- 12.5 -(50) +40 isobutyrate HCl dl-Adrenaline 3,4-O--di- 3.1 +(50) +35 pivalate hydrochloride ______________________________________ .sup.1 Concentrations causing an increase in pupil diameter of comparable degree (approximately 1 mm). .sup.2 + present; - absent. .sup.3 Instillation of 0.1 ml of 0.5 M solution.
The results shown in Table 1 prove that ibopamine is endowed with high mydriatic effect, wit

REFERENCES:
patent: 3959485 (1976-05-01), Windheuser
patent: 4218470 (1980-08-01), Casagrande et al.
patent: 4275074 (1981-06-01), Langham et al.
patent: 4628064 (1986-12-01), Casagrande et al.
Ocular Pharmacology--4th Ed.--1978, The C.V. Mosby Co.--St. Louis, MO.--p. 237.

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