United States Patent 3,644,643 METHOD OF REDUCING INTRAOCULAR PRESSURE USING GLYCINE John C. Krantz, Jr., Gibson Island, Md., assiguor to Unimed, Inc., Morristown, NJ. N0 Drawing. Filed Oct. 13, 1969, Ser. No. 865,946 Int. Cl. A61k 27/00 US. Cl. 424-319 3 Claims ABSTRACT OF THE DISCLOSURE Intraocular pressure or intraocular tension is reduced in patients, for example those suffering from glaucoma or preoperatively to reduce intraocular tension prior to cataract surgery, e.g. intracapsular cataract extraction so as to facilitate the operative procedure, is reduced according to the invention by the administration to the patient of an effective amount of glycine. The glycine can be administered orally or by injection, oral administration being preferred.
BACKGROUND OF THE INVENTION Excessive intraocular pressure occurs in certain abnormal eye conditions, particularly glaucoma. As a matter of fact, glaucoma is often defined as a pathologic state in which the intraocular pressure is elevated, intermittently or constantly, to a level which the eye cannot withstand without damage to structure or impairment of function. Therefore, in the treatment of glaucoma it is most desirable to reduce the intraocular pressure back to a normal state.
It is also desirable for the ophthalmologist to try to lower ocular tension not only in the medical treatment of glaucoma but also prior to surgical treatment. Also, in the case of intracapsular cataract extraction it is desirable to reduce the intraocular pressure prior to the surgery.
The most effective agent for this purpose is glycerin, which is generally administered in an amount of 1-2 gm./kg. of body weight, mixed with an equal amount of water. However, patients, are unable to tolerate glycerin for more than two or three days because of gastric problems such as vomiting and nausea which is caused by it. Another drug which has been used for this purpose is acetazolamide, but this drug also causes vomiting or nausea and its use is therefore considerably limited.
This invention is therefore concerned with the provision of an efficient and safe agent for reduction of intraocular pressure, which agent can be taken over prolonged periods of time and which can be administered by injection of orally.
SUMMARY OF THE INVENTION Generally speaking, the present invention relates to a method of reducing intraocular pressure, which comprises administering an intraocular pressure reducing effective amount of glycine. The method of administration is preferably oral, though administration by injection, for example intravenous administration, is also suitable.
It is a primary object of the present invention to provide compositions and treatments for reduction of introocular pressure with safety from the standpoint of lack of toxicity and lack of undesired side effects.
It is another object of the present invention to provide compositions and treatments for reducing intraocular pressure permitting the use thereof in the treatment of glaucoma and other conditions requiring reduced intraocular pressure by oral administration of safe and effective amounts of glycine which is substantially as ef- 3,644,543 Patented Feb. 22, 1972 fective as glycerin without any of the undesired side effects thereof.
Other objects and advantages of the present invention will be apparent from a further reading of the specification and of the appended claims.
Glycine is the common term for aminoacetic acid. It is classified as a non-essential amino acid based on its growth effect in rats, and it has demonstrated very little pharmacological activity, being used primarily as a dietary supplement.
However, I have discovered that glycine is highly effective in reducing intraocular pressure, and in view of the fact that oral doses of glycine are well tolerated, with no adverse effects, the glycine can be used over prolonged periods of time for situations wherein reduction of intraocular pressure is desired.
The glycine may be administered in capsules, in tablets prepared therefrom either alone or with a pharmaceutically acceptable carrier, or in solutions thereof, all of these for oral administration, and in addition, solutions can be prepared for objection purposes.
The dosage may vary within rather wide limits, and the general dosage for patients to effect reduction of intraocular pressure is from about 25-100 grams per day, the most preferred dosage being about 50 grams per day. The unit dosage may be from about 5-50 grams, the preferred dosage being about 25 grams administered twice a day.
DESCRIPTION OF PREFERRED EMBODIMENTS The following examples are given to further illustrate the invention. The scope of the invention is not, however, meant to be limited to the specific details of these examples.
EXAMPLE 1 Gelatin capsules are filled with 10 grams each of glycine. One capsule administered orally three times a day constitutes an average daily dose for the reduction of intraocular pressure.
EXAMPLE 2 Tablets are prepared using normal tabletting procedure, each tablet containing 12.5 grams of glycine. Two of the tablets twice a day constitutes an average dose for the reduction of intraocular pressure. For severe conditions two tablets given four times a day may be administered.
EXAMPLE 3 The following describes oral administration of glycine evaluated in regard to its effect on the normal intraocular pressure of the rabbit.
Materials and methods Five male New Zealand albino rabbits, ranging in weight from 3.1 to 3.9 kg., were utilized for the study.
All intraocular pressure measurement were made with an Improved Lawton Shioetz Tonometer, using a 5.5 gram weight. Six readings, 3 on each eye, were taken on all rabbits at each time interval. The average of these 6 readings represented one intraocular pressure measurement. Tetracaine hydrochloride, 0.5%, was used to anesthetize both eyes prior to each series of measurements.
A 61.25% (w./v.) suspension of glycine in distilled Water was administered, via stomach tube, to all 5 rabbits. Tragacanth (0.2%) was used as the suspending agent. Each rabbit received 2.45 gm./kg. of glycine in a volume dose of 4 ml./kg.
Three control and eleven treatment intraocular pressure measurements were obtained for each rabbit. Control measurements were taken at 30, 15 and minutes. Tonometric measurements after glycine administration were taken every 30 minutes for the first 4 hours. Additional measurements were taken at 5, 24 and 48 hours.
Results and discussion In Table 1 are listed the individual and mean intraocular pressure measurements before and after oral administration of glycine. Also shown is the statistical analysis of variance between means values and the value of 4 minutes were significantly different (P 5%) from the TABLE 1 Individual and mean intraocular pressure measurements before and after oral administration of glycine (2.45 gmJkg.)
Difierence Rabbit (mm. Hg) lrom control Mean S. mean No. 1 No. 2 N o. 3 N o. 4 No. 5 (mm. Hg) (mm. Hg)
l Denotes significant difference from control mean. Analysis of variance:
Source 01 Degrees of Sum of Mean F variation freedom squares square ratio Rabbits 4 423. 31 105. 83 Times 11 657. 95 59. 81 12. 49 Error 44 210. 93 4. 79
Total 59 1, 292. 19 21. 90
Norn.-Least significant difierence between control and treatment means at the 5% confidence level:
D=Qx7 Error mean square least significant difference between the control means and treatment means at the 5% level of confidence.
As is evident from the data, glycine markedly decreased intraocular pressure in all rabbits. Within minutes after administration the intraocular pressure of the 5 animals had decreased an average of 6.1 mm. Hg. The maximum effect was observed at 120 minutes, when the pressures averaged 10.4 mm. Hg below that of the control. At 5 hours the mean intraocular pressure had returned to within 3.0 mm. Hg of the control mean. Similar measurements, slightly' below original control values, were also obtained at 24 and 48 hours after administration.
Statistical treatment of the data revealed that the mean intraocular pressures from 30 minutes through 240 No. obs/time What is claimed is: 1. Method of reducing intraocular pressure, which comprises administering to a patient requiring reduction 50 of intraocular pressure an effective amount of glycine.
References Cited Takagaki, Chem. Abst. vol. 59 (1963), p. 4399b. Kubena et al., Chem. Abst. vol. 64 (1966), p. 203680.
60 SAM ROSEN, Primary Examiner