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Arginyl-glutamine dipeptide for treatment of pathological vascular proliferation

a technology of arginylglutamine and dipeptide, which is applied in the direction of peptide/protein ingredients, drug compositions, and metabolic disorders, can solve the problems of impaired vision, many challenges for people with visual impairment, and inability to fully enjoy the visual aspects of their surroundings, so as to prolong the life of diabetics and achieve the effect of high survival rate of very premature infants

Inactive Publication Date: 2005-04-28
BRISTOL MYERS SQUIBB CO
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The invention provides a way to prevent the growth of abnormal blood vessels, which can be beneficial for treating certain eye conditions. The invention uses a combination of two amino acids, arginine and glutamine, in a safe and easily absorbable form. This combination, known as arginyl-glutamine, has been found to inhibit the growth of unwanted blood vessels. The invention also describes how to formulate the compounds for pharmaceutical use, as well as for nutraceutical use. The technical effect of the invention is to provide a safe and effective way to prevent the growth of abnormal blood vessels.

Problems solved by technology

People suffering from visual impairment face many challenges in performing routine daily activities and / or may not be able to fully enjoy the visual aspects of their surroundings.
Diabetic retinopathy results in impairment of a person's vision causing severely blurred vision and, potentially, blindness.
Diabetics are faced with numerous complications including kidney failure, non-traumatic amputations, an increase in the incidence of heart attack or stroke, nerve damage, and loss of vision.
However, the longer a person has diabetes the greater the chances of developing diabetic retinopathy.
While management of diabetic retinopathy has improved, risk of complications, such as loss of visual acuity, loss of night vision and loss of peripheral vision, remains significant and treatment sometimes fails.
Unfortunately, current treatment options are inadequate and the disease is often progressive even with successful glucose control.
In premature babies, this process is not complete and the abnormal growth of the vessels proliferate leading to scar tissue development, retinal detachment and possibly complete blindness.
Ironically, however, increasing rates of survival of very premature infants, who would have had little chance of survival in the past, has increased the occurrence of retinopathy of prematurity.
Experiments involving the use of total parenteral nutrition (TPN) containing glycyl-glutamine dipeptides, however, suggest potential adverse effects of the TPN formulation containing glycyl-glutamine (U.S. Pat. No. 5,189,016).
Although treatment options, such as laser therapy, exist for both conditions, the results are inadequate and the disease often remains progressive.

Method used

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  • Arginyl-glutamine dipeptide for treatment of pathological vascular proliferation
  • Arginyl-glutamine dipeptide for treatment of pathological vascular proliferation

Examples

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Effect test

example 1

Use of Arginyl-glutamine to Prevent Retinopathy of Prematurity

[0100] Neonatal mice were exposed to a period of hyperoxia to induce retinal angiogenesis that mimics retinopathy of prematurity. An Arginyl-glutamine dipeptide was administered intraperitoneally twice daily during the period when neovascularization occurs in this model, days 12 through 17.

[0101] On day 17 the animals are sacrificed and degree of angiogenesis was quantified by counting pre-retinal neovascularization on stained sections from treated and untreated animals.

[0102] The data summarized in FIG. 1 represent combined data from two separate experiments. The results demonstrated a statistically significant effect of the dipeptide (argininyl-glutamine) compared to vehicle and dipeptide (alaninyl-glycine). Treatment of the pups with the dipeptide (argininyl-glutamine) resulted in a 80% reduction in preretinal neovascularization.

[0103] This experiment has been repeated with different doses of the dipeptide compared...

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Abstract

The subject invention provides dipeptides useful in preventing pathological proliferation of blood vessels. The dipeptides of the subject invention are particularly advantageous because they are stable, bioavailable, and can be formulated in an aqueous solution, and in particular, into infant formulations.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of U.S. provisional application Ser. No. 60 / 506,413, filed Sep. 26, 2003.BACKGROUND OF THE INVENTION [0002] People suffering from visual impairment face many challenges in performing routine daily activities and / or may not be able to fully enjoy the visual aspects of their surroundings. Of particular concern with regard to the current invention are visual impairments caused by damage to the retina, which occur in conditions such as diabetic retinopathy and retinopathy of prematurity. [0003] Diabetic retinopathy is a progressive disease characterized by abnormalities of the blood vessels of the retina caused by diabetes, such as weakening of the blood vessel walls, leakage from the blood vessels, and bleeding and scarring around new vessels. Diabetic retinopathy results in impairment of a person's vision causing severely blurred vision and, potentially, blindness. [0004] Diabetes affects over 16 millio...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A23L1/305A61K38/04A61K38/05A61K38/16A61K47/00A61P9/10
CPCA23L1/3053A61K38/16A61K38/05A61K38/04A23L33/18A61P9/10
Inventor NEU, JOSEFGRANT, MARIA B.ANTHONY, JOSHUA C.
Owner BRISTOL MYERS SQUIBB CO
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