US3644643A - Method of reducing intraocular pressure using glycine - Google Patents
Method of reducing intraocular pressure using glycine Download PDFInfo
- Publication number
- US3644643A US3644643A US865946A US3644643DA US3644643A US 3644643 A US3644643 A US 3644643A US 865946 A US865946 A US 865946A US 3644643D A US3644643D A US 3644643DA US 3644643 A US3644643 A US 3644643A
- Authority
- US
- United States
- Prior art keywords
- glycine
- intraocular pressure
- administration
- intraocular
- glaucoma
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 title abstract description 48
- 230000004410 intraocular pressure Effects 0.000 title abstract description 29
- 239000004471 Glycine Substances 0.000 title abstract description 23
- 238000000034 method Methods 0.000 title abstract description 9
- 208000010412 Glaucoma Diseases 0.000 abstract description 7
- 208000002177 Cataract Diseases 0.000 abstract description 4
- 238000002347 injection Methods 0.000 abstract description 4
- 239000007924 injection Substances 0.000 abstract description 4
- 238000001356 surgical procedure Methods 0.000 abstract description 4
- 238000000605 extraction Methods 0.000 abstract description 3
- 229960002449 glycine Drugs 0.000 description 21
- 241000283973 Oryctolagus cuniculus Species 0.000 description 9
- 238000011282 treatment Methods 0.000 description 9
- 230000000694 effects Effects 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol group Chemical group OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 238000009530 blood pressure measurement Methods 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 206010028813 Nausea Diseases 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 230000008673 vomiting Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- PPWHTZKZQNXVAE-UHFFFAOYSA-N Tetracaine hydrochloride Chemical compound Cl.CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 PPWHTZKZQNXVAE-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- BZKPWHYZMXOIDC-UHFFFAOYSA-N acetazolamide Chemical group CC(=O)NC1=NN=C(S(N)(=O)=O)S1 BZKPWHYZMXOIDC-UHFFFAOYSA-N 0.000 description 1
- 229960000571 acetazolamide Drugs 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000013905 glycine and its sodium salt Nutrition 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004493 normal intraocular pressure Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229960002494 tetracaine hydrochloride Drugs 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
Definitions
- 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.
- glycerin which is generally administered in an amount of 1-2 gm./kg. of body weight, mixed with an equal amount of water.
- glycerin is generally administered in an amount of 1-2 gm./kg. of body weight, mixed with an equal amount of water.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- D Qx7 Error mean square least significant difference between the control means and treatment means at the 5% level of confidence.
- Method of reducing intraocular pressure which comprises administering to a patient requiring reduction 50 of intraocular pressure an effective amount of glycine.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
INTRAOCULAR PRESSURE OR INTRAOCULAR TENSION IS REDUCED IN PATIENTS, FOR EXAMPLE THOSE SUFFERING FROM GLAUCOMA OR PREOPERATIVELY TO REDUCE INTRAOCULR TENSION PRIOR TO CATRACT SURGERY, E.G. INTRACAPSUL CATARACT EXTRACTION SO AS TO FICILITATE 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.
Description
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
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US86594669A | 1969-10-13 | 1969-10-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3644643A true US3644643A (en) | 1972-02-22 |
Family
ID=25346580
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US865946A Expired - Lifetime US3644643A (en) | 1969-10-13 | 1969-10-13 | Method of reducing intraocular pressure using glycine |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US3644643A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2377197A1 (en) * | 1977-01-13 | 1978-08-11 | Hoffmann La Roche | DIAGNOSIS PROCESS FOR DETECTING A FAILURE OF ABSORPTION OF AMINO ACIDS, SUGARS, FATS, VITAMINS AND MINERAL SALTS |
| FR2437834A1 (en) * | 1978-10-04 | 1980-04-30 | Lejeune Jerome | L-serine or glycine for treatment of cerebral deficiencies - such as mongolism and general mental debility, etc. |
| WO1993018762A3 (en) * | 1992-03-19 | 1993-10-28 | Allergan Inc | Method for reducing intraocular pressure in the mammalian eye by administration of gamma aminobutyric acid (gaba) agonists |
| RU2203179C2 (en) * | 1999-01-14 | 2003-04-27 | Нефедов Борис Вениаминович | Installation for cutting porous concrete blocks |
| WO2012166533A1 (en) * | 2011-05-27 | 2012-12-06 | Allergan, Inc. | D-serine transporter inhibitors as pharmaceutical compositions for the treatment of visual system disorders |
| WO2012174243A1 (en) * | 2011-06-17 | 2012-12-20 | Allergan, Inc. | D -serine for the treatment of visual system disorders |
| US11407812B2 (en) * | 2015-10-01 | 2022-08-09 | Goleini Inc. | Targeted expression of chloride channels and methods of use thereof |
-
1969
- 1969-10-13 US US865946A patent/US3644643A/en not_active Expired - Lifetime
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2377197A1 (en) * | 1977-01-13 | 1978-08-11 | Hoffmann La Roche | DIAGNOSIS PROCESS FOR DETECTING A FAILURE OF ABSORPTION OF AMINO ACIDS, SUGARS, FATS, VITAMINS AND MINERAL SALTS |
| FR2437834A1 (en) * | 1978-10-04 | 1980-04-30 | Lejeune Jerome | L-serine or glycine for treatment of cerebral deficiencies - such as mongolism and general mental debility, etc. |
| WO1993018762A3 (en) * | 1992-03-19 | 1993-10-28 | Allergan Inc | Method for reducing intraocular pressure in the mammalian eye by administration of gamma aminobutyric acid (gaba) agonists |
| US6077839A (en) * | 1992-03-19 | 2000-06-20 | Allergan Sales, Inc. | Method for reducing intraocular pressure in the mammalian eye by administration of gamma aminobutyric acid (GABA) agonists |
| RU2203179C2 (en) * | 1999-01-14 | 2003-04-27 | Нефедов Борис Вениаминович | Installation for cutting porous concrete blocks |
| WO2012166533A1 (en) * | 2011-05-27 | 2012-12-06 | Allergan, Inc. | D-serine transporter inhibitors as pharmaceutical compositions for the treatment of visual system disorders |
| US8735451B2 (en) | 2011-05-27 | 2014-05-27 | Allergan, Inc. | D-serine transporter inhibitors as pharmaceutical compositions for the treatment of visual system disorders |
| US9415031B2 (en) | 2011-05-27 | 2016-08-16 | Allergan, Inc. | D-serine transporter inhibitors as pharmaceutical compositions for the treatment of visual system disorders |
| WO2012174243A1 (en) * | 2011-06-17 | 2012-12-20 | Allergan, Inc. | D -serine for the treatment of visual system disorders |
| US11407812B2 (en) * | 2015-10-01 | 2022-08-09 | Goleini Inc. | Targeted expression of chloride channels and methods of use thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1315505B1 (en) | Pharmaceutical compositions for headache, migraine, nausea and emesis | |
| US5547993A (en) | Therapeutic agent for glaucoma | |
| JPH04502161A (en) | Uses of acetyl D-carnitine in therapeutic treatment of glaucoma | |
| JPS62178514A (en) | Agent for lowering intraocular pressure | |
| AU2001286178A1 (en) | Pharmaceutical compositions for headache, migraine, nausea and emesis | |
| CA1157379A (en) | Method of preparation of pharmaceutical composition for treating peripheral orthostatic hypotention | |
| US4438138A (en) | Reduction of cholesterol with meta-chloro α-t-butylaminopropiophenone | |
| US3644643A (en) | Method of reducing intraocular pressure using glycine | |
| US4278679A (en) | Combination of two or more drugs in a single dosage form wherein one of the drugs is a physostigmine compound | |
| JPS63270626A (en) | Antiulcer agent | |
| WO2005084392A2 (en) | 4-methylpyrazole formulations for inhibiting ethanol intolerance | |
| US5519030A (en) | Method for prophylaxis and treatment of myopia | |
| Bharani | Sexual dysfunction after gemfibrozil | |
| JPH08239327A (en) | Agent for preventing or treating chronic skeletal muscle pain | |
| US3932652A (en) | Antidepressant compositions | |
| US3360434A (en) | Method for reducing blood pressure with phenylalanine derivatives | |
| AU2012276476B2 (en) | Pharmaceutical composition for treating premature ejaculation and method for treating premature ejaculation | |
| EP0256629A2 (en) | Tolrestat or a salt thereof as an immuno-stimulating agent | |
| CA1110170A (en) | Antihypertensive compositions | |
| JPS63502270A (en) | Ophthalmic pharmaceutical composition having mydriatic effect | |
| Stinson et al. | Ventricular asystole and overdose with atenolol | |
| Morton et al. | Cortical blindness after nifedipine treatment | |
| Gray et al. | Protoveratrine A in treatment of hypertension | |
| RU2275905C2 (en) | Pharmaceutical compositions against headache, migraine, sickness, and retch | |
| US3786157A (en) | Method of treating hyperglycemia |