IL29570A - Compositions for the treatment of glaucoma containing 5,10-epoxy-5h-dibenzo(a,d)cycloheptene derivatives - Google Patents

Description

Compositions of Cs 27999 The present invention relates to topical opthalmic compositions useful in the treatment of More this invention relates to agents which effectively lower intraocular pressure and to methods for the preparation of such Present therapeutic methods for the treatment of glaucoma predominantly involve the use of carbonic anhydrase inhibitors and Of these methods the most widely employed for glaucoma therapy is the topical use of pilocarpine being the most usually employed This drug generally requires an undesirable frequency of generally around the tolerance to the requiring increasingly stronger often up to the highest dosage level and tachyphylaxis are not uncommon Carbonic anhydrase inhibitors are generally not employed as a sole therapeutic but ly are used concomitantly with miotics in the treatment of chronic glaucoma or preparatory to Surgery is usually reserved for those cases of chronic glaucoma that do not v spond to drug therapy or for the treatment of the somewhat uncommon acute congestive To complete the picture of presently available methods for the treatment of one should mention the These topical preparations are longer lasting therapeutically than but produce intense occasional iris cysts and have associated with parasympathomimetic systemic it can be mentioned that miotics produce a miosis which is generally annoying to the patient because of interference with is quite obvious that there is an outstanding need for new therapeutic agents which can be employed in the treatment of glaucoma and which avoid some or all of the disadvantages of the presently available It a significant purpose of this invention to provide such novel ration to the eye in a dosage form that will significantly lower intraocular pressure while achieving the pupillary goals of a submaximally dilated and mobile retaining sensitivity to stimulation by These and other objects of this vention appear more fully The topical compositions of this tion contain one of the following compounds as novel ocular hypotensive agents 5 heptene in a conventional topical opthalmic vehicle and in an tive dosage range which upon ocular introduction will lower intraocular Although the above formulae show the free it is to be understood that the acid addition such as hydrochloride or are equivalent for the purposes of this Although compositions of this invention wherein the novel hypotensive agents form the only active ingredient tively lower intraocular for some purposes it may be desirable to combine treatment with exogenous sympathomimetic one embodiment the sympathomimetic amine can be administered with the intraocular hypotensive agent of this invention in a single vehicle in dosages which effectively lower intraocular Exemplary of such sympathomimetic amines are norepinephrine and In another embodiment the sympathomimetic amine can be ed following instillation of the novel hypotensive agent of this The compositions of this invention are administered topically to the either in the form of or as opthalmic Formulations are herein expressed as percent weight by volume and generally the dosages for the intraocular hypotensive agent fall within the range of to Higher as for up to about or lower dosages can be provided the dose is effective in lowering intraocular is and achieves the desired pupillary goals previously set The procedure for the preparation of the compounds of our Israel Patents 26263 and 21455 Claim 1 as set forth in The sympathomimetic epinephrine and norepinephrine as well as isoproterenol are well known in the art and their properties and method of preparation can be found in standard references for the Merck 7th edition The compositions of this invention are incorporated into a sterile opthalmic Such vehicles are well known t 1 in the art and are fully described in such standard reference 2 works as Remington s Pharmaceutical Martin and 3 Mack Publishing 13th edition The 4 ing is a suitable percentages in the following 5 examples refer to a percent weight by 6 Sterile Vehicle 7 sulfate 8 Sodium bisulfite 9 Phenylmercuric acetate 10 Sodium hydroxide or 11 chloric acid to pH 12 Water ad 13 In the foregoing composition the 14 and the sodium bisulfite act as and can vary 15 fold former up to about and the latter down to about 16 In addition to these specific any 17 opthalmic can be These are more fully 18 described in Remington 19 Phenyl mercuric acetate is employed as a 20 Any preservative suitable for opthalmic formulation 21 such as those described in Remington can be 22 Although the pH of the foregoing sterile vehicle is 23 adjusted using base or acid it should be recognized that 24 ard buffering agents such as those described in Remington 25 or in the Merck Volume 7 so long as these 26 ing agents are suitable for opthalmic can be 27 Thus a pH range from about can be 28 although pH within the physiological range is when 29 employing a buffered system it is preferred to utilize a pH 30 of about to about With a buffered system pH is time altering the ratio of the buffered tonicity so as to maintain an isotonic Although buffers can be used at varying when pH is less than sodium hydroxide or hydrochloric acid can conveniently be employed to adjust the When using a buffered system it is preferred to adjust the range to that of the physiological pH range of about 6 to or Patent sets forth suitable sterile vehicles for especially when a catechol such as is employed in the compositions of this The following Examples demonstrate various tions of the compositions of this Example 1 oxime hydrogen maleate Oxine sulfate Sodium bisulfite Boric acid Sodium borate Phenylmercuric acetate Water ad Example II Trans dibenzo cycloheptene hydrogen maleate Oxine sulfate Sodium bisulfite Boric acid Sodium borate Phen lmercuric acetate Example III Epinephrine oxine hydrogen maleate Boric acid Sodium borate Oxine sulfate Phenylmercuric acetate Sodium bisulfite Water ad Example IV Epinephrine Trans dibenzo cycloheptene hydrogen maleate Boric acid Sodium borate Oxine sulfate Phenylmercuric acetate Sodium bisulfite Water ad The compositions of this invention can also be ministered as These are for by mixing finely milled powdered ingredients with a small amount of white petrolatum and levigating or otherwise mixing until a uniform distribution is The balance of white petrolatum is added by geometric addition until the desired dosage form is insufficientOCRQuality

Claims (2)

SLAIMS :

1. An anti-glaucoma topical opthalmic composition comprising 10, ll-dihydro-5- (3-dimethylaminopropyl) -5,10-epoxy-5H-dibenzo [a,d] cycloheptene-ll-one oxime or trans 10,11-dihydro-5- (3-methylaminopropyl) -5,10-epoxy-ll-hydroxy-5H-dibenzo [a,d] cycloheptene, and their non-toxic acid addition salts. 2 —Λ mo hod for lowering intraocular pressuj

2. · A process for preparing an antiglaucoma composition which comprises incorporating a compound selected from 10,ll-dihydro- - (3-methylaminopropyl)-5»10 epoxy-11-hydroxy-5H-dibenzo a,d7cycloheptene or 10,ll-dihydro-5>-(3-dimethylaminopropyl)- #10-epoxy-5H-dibenzo- a,d7cycloheptene-11-one in a topical ophthalmic vehicle in a concentration of at least 0e01# weight by volume,, Dated this 3rd March 1968