Method of treating vascular proliferative responses

Details Method of treating vascular proliferative responses Method of treating vascular proliferative responses

1999-03-08

2001-05-15

Kulkosky, Peter F. (Department: 1615)

Drug, bio-affecting and body treating compositions

Solid synthetic organic polymer as designated organic active...

C424S900000, C424S900000

Reexamination Certificate

active

06231847

ABSTRACT:

FIELD OF THE INVENTION
This invention relates to a method of treating vascular proliferative responses.
BACKGROUND OF THE INVENTION
Vascular proliferative disorders are conditions within the walls of blood vessels, including arteries and veins, which result in occlusion or blockage of blood flow. A common vascular proliferative disorder is restenosis. Restenosis is a major clinical problem associated with coronary angioplasty and other medical procedures. Restenosis generally occurs within about 0 to 6 months in about 30% to 50% of patients who undergo balloon angioplasty to clear clogged coronary arteries in an effort to prevent and treat heart disease due to occluded arteries. The resulting restenosis causes substantial patient morbidity and health care expenses.
The process of restenosis is initiated by injury of the vessel, with the subsequent release of thrombogenic, vasoactive, and mitogenic factors. Endothelial and deep-vessel injury leads to platelet aggregation, thrombus formation, inflammation, and activation of macrophages and smooth-muscle cells. These events induce the production and release of growth factors and cytokines, which in turn may promote their own synthesis and release from target cells Thus, a self-perpetuating process is initiated.
There currently are no effective treatments available for restenosis. Accordingly, a major medical need exists for effective treatments for restenosis and other vascular proliferative disorders. We have now discovered that poly(arginine) can be used to treat vascular proliferative disorders such as restenosis.
SUMMARY OF THE INVENTION
Provided by the present invention is a method of inhibiting a vascular proliferative response in a patient that comprises intravenously administering to the patient a proliferative response inhibiting amount of poly(arginine).
In one embodiment of the invention, the patient is a patient who is to undergo or who has undergone angioplasty.
In another embodiment of the invention the patient is a patient who is to undergo or who has undergone a graft.
In another embodiment of the invention, the patient is a patient who is to undergo or who has undergone a shunt.
In another embodiment of the invention, the patient is a patient who is to undergo or who has undergone a transplant.
In a preferred embodiment of the invention, the proliferative response is restenosis.
In one embodiment of the invention, the poly(arginine) is a homopolymer.
In another embodiment of the invention, the poly(arginine) is a copolymer.
In another embodiment of the invention, the poly(arginine) has a weight-average molecular weight in the range of about 5,000 to about 30,000.
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides a method of treating a vascular proliferative response in a patient, the method comprising intravenously administering to the patient a proliferative response inhibiting amount of poly(arginine).
The term “treating” means to ameliorate the symptoms of a proliferative response. The term treating also includes the prophylactic inhibition of a proliferative response. Poly(arginine) can be administered to a patient who is undergoing a proliferative response, such as a patient who is suffering from restenosis. In addition, certain patients are at risk of undergoing a proliferative response. Those patients include, but are not limited to, patients who have undergone or who will undergo balloon angioplasty, or graft, shut or transplant procedures. In such cases, it is desirable to administer poly(arginine) as a prophylactic measure to help inhibit a proliferative response or to ameliorate the symptoms of a proliferative response that has commenced.
The term “patient” means all animals, including humans. The patients to be treated by the present method are patients who suffer from a proliferative response or who are at risk for having a proliferative response. Those skilled in the art are readily able to identify patients who suffer from a proliferative response. For example, restenosis results in a blockage of a blood vessel. Thus, the presence of restenosis may be determined by observing the blood flow in the blood vessels, which is a common practice that is well know to those skilled in the art. The patients at risk for having a proliferative response include patients who have undergone or who are to undergo a medical procedures such as angioplasty, grafts, shunts or transplants, among others.
The poly(arginine) is administered to the patient in a proliferative response inhibiting amount. The amount of poly(arginine) administered will vary with each patient to be treated, and the amount can depend on the weight of the patient, and the severity of the proliferative response, among other factors. The amount of poly(arginine) administered to a patient can readily be determined by one skilled in the art by simply administering a quantity of poly(arginine) and observing the results. For example, in a patient having restenosis, poly(arginine) is administered and the rate of blood vessel occlusion monitored by watching the blockage of blood flow in the vessel.
An example of a suitable dosage of poly(arginine) for a typical human patient is a dose the range of about 10 mg/day to about 10,000 mg/day. Preferably, the dosage is in the range of about 100 mg/day to about 2,000 mg/day.
The poly(arginine) is administered intravenously to the patient. The administration can be at once or over a period. If over a period, the poly(arginine) can be administered in several finite quantities or continuously. Preferably, the poly(arginine) is administered continuously over a period.
The term “poly(arginine)” means a polymer that contains the amino acid monomer arginine. The poly(arginine) can be a homopolymer made solely of arginine or a copolymer that contains arginine monomer units. The copolymer can be any type of copolymer including graft, block or random copolymers, among others. For example, the poly(arginine) copolymer may contain other amino acid monomers such as lysine or histidine. Similarly, the poly(arginine) copolymer may contain monomers such as vinyl acetate, which can be hydrolyzed to give vinyl alcohol. It is noted that any physiologically acceptable monomer may be part of the copolymer along with the monomer arginine. In a most preferred embodiment, the poly(arginine) is a homopolymer.
The weight-average molecular weight of the poly(arginine), whether copolymer or homopolymer, is typically in the range of about 2,000 to about 100,000. Preferably, the weight-average molecular weight of the poly(arginine) is in the range of about 5,000 to about 30,000. Most preferably the poly(arginine) has a weight-average molecular weight in the range of about 8,000 to about 12,000.
Poly(arginine) homopolymer can be easily prepared by methods well known to those skilled in the art or can be obtained from Sigma Chemical Company, St. Louis, Mo. Similarly, the synthesis of poly(arginine) copolymers are well known to those skilled in the art.
When the poly(arginine) is a copolymer, the amount of arginine found in the polymer is in the range of about 1% to about 99% by weight of the copolymer. Preferably, the arginine is found in the range of about 30% to about 99% by weight of the copolymer. Most preferably, the poly(arginine) is found in the range of about 50% to about 99% by weight of the copolymer.
The poly(arginine) is typically administered to the patient as part of a pharmaceutically acceptable solution. Compositions suitable for administration may comprise physiologically acceptable sterile aqueous or nonaqueous solutions. Examples of suitable aqueous and nonaqueous carriers, diluents, solvents or vehicles include water, saline, ethanol, polyols (propyleneglycol, polyethyleneglycol, glycerol, and the like), suitable mixtures thereof, vegetable oils (such as olive oil) and injectable organic esters such as ethyl oleate.
These compositions may also contain adjuvants such as preserving, wetting, emulsifying, and dispersing agents. Prevention of the action of microorganisms can be ensured by various antibacteria

Affiliated with

Also associated with

Rating

Method of treating vascular proliferative responses does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Method of treating vascular proliferative responses, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method of treating vascular proliferative responses will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2455197