US2006034822A1PendingUtilityA1
Hyaluronidase preparation for ophthalmic administration and enzymatic methods for accelerating clearance of hemorrhagic blood from the vitreous body of the eye
Est. expiryNov 22, 2015(expired)· nominal 20-yr term from priority
Inventors:Hampar L. KarageozianVicken H. KarageozianMaria KenneyJose Luis Gutierrez FloresGabriel Arturo Carpio AragonAnthony B. Nesburn
A61K 31/7016A61P 27/00A61P 27/02A61K 38/47A61K 38/43
63
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Claims
Abstract
A thimerosal-free hyaluronidase preparation wherein the preferred hyaluronidase enzyme is devoid of molecular weight fractions below 40,000 MW, between 60-70,000 MW and above 100,000 MW. Also disclosed is a method for accelerating the clearance of hemorrhagic blood from the vitreous humor of the eye, said method comprising the step of contacting at least one hemorrhage-clearing enzyme (e.g., a β-glucuronidase, matrix metalloproteinase, chondroitinase, chondroitin sulfatase or protein kinase) with the vitreous humor in an amount which is effective to cause accelerated clearance of blood therefrom.
Claims
exact text as granted — not AI-modified1 . A method for accelerating the clearance of hemorrhagic blood from the vitreous humor of a mammalian eye, said method comprising the step of:
contacting with said vitreous humor an amount of an enzyme which is active to accelerate the clearance of hemorrhagic blood from the vitreous humor.
2 . The method of claim 1 wherein said enzyme is selected from the group consisting of:
hyaluronidase; keratinase; chondroitinase AC; chondroitinase B; chondroitinase ABC; chondroitin 4 sulfatase; chondroitin 6 sulfatase; matrix metalloproteinase-1; matrix metalloproteinase-2; matrix metalloproteinase-3; matrix metalloproteinase-9; streptokinase; urokinase; and, combinations thereof.
3 . The method of claim 1 wherein said enzyme is a β-glucuronidase enzyme.
4 . The method of claim 1 wherein said enzyme is a matrix metalloproteinase enzyme.
5 . The method of claim 1 wherein said enzyme is a protein kinase enzyme.
6 . The method of claim 1 wherein said enzyme is a chondroitin sulfatase enzyme.
7 . The method of claim 1 wherein said enzyme is in liquid solution, and wherein the step of contacting of said enzyme with the vitreous humor comprises:
injecting said liquid solution into the vitreous humor.
8 . The method of claim 1 wherein said enzyme is hyaluronidase.
9 . The method of claim 8 wherein said amount of said hyaluronidase enzyme is 10-300 International Units.
10 . The method of claim 1 wherein said enzyme is administered in a single intravitreal injection.
11 . The method of claim 10 herein the single intravitreal injection has an injectate volume of less than 50 μl.
12 . The method of claim 8 wherein said hyaluronidase enzyme is devoid of molecular weight fractions above 100,000 MW.
13 . The method of claim 8 wherein said hyaluronidase is devoid of hyaluronidase molecular weight fractions below 40,000 MW.
14 . The method of claim 8 wherein said hyaluronidase is devoid of molecular weight fractions between 60,000-70,000 MW.
15 . The method of claim 8 wherein said hyaluronidase is devoid of molecular weight fractions above 100,000 MW below 40,000 MW and between 60,000-70,000 MW.
16 . The method of claim 8 wherein hyaluronidase enzyme is devoid of gelatinolytic hyaluronidase having molecular weights between approximately 60,000-100,000 MW.
17 . The method of claim 8 wherein said hyaluronidase enzyme is devoid of caseinolytic hyaluronidase having molecular weight above approximately 45,000 MW.
18 . The method of claim 8 wherein said hyaluronidase enzyme is devoid of hyaluronic acid lysing hyaluronidase having molecular weights above approximately 100,000 MW.
19 . The method of claim 1 wherein said method further comprises:
contacting said enzyme with said vitreous humor in the absence of thimerosal.
20 . The method of claim 8 wherein said hyaluronidase enzyme is prepared in a solution for injection which is free of thimerosal and which has the general formulation:
Hyaluronidase (ACS)
0-8000 I.U.;
Lactose, USP
13.3 mg; and
Phosphate, USP
5 mmoles;
and, wherein the hyaluronidase enzyme is devoid of molecular weight fractions below 40,000.
21 . The method of claim 20 wherein said solution for injection has the following specific formulation:
Hyaluronidase (ACS)
7,200 I.U.;
Lactose, USP
13.3 mg; and
Phosphate, USP
5 mmoles.
22 . The method of claim 20 wherein said solution for injection is dissolved in balanced salt solution.
23 . A hyaluronidase preparation for ophthalmic administration, said preparation being free of thimerosal and free of hyaluronidase which is less than 40,000 MW.
24 . The preparation of claim 23 wherein said preparation is further free of hyaluronidase having molecular weights between 60,000-70,000 MW.
25 . The preparation of claim 23 wherein said preparation is further free of hyaluronidase having a molecular weight in excess of 100,000 MW.
26 . The preparation of claim 23 wherein said preparation is further devoid of hyaluronic acid lysing hyaluronidase having molecular weight above approximately 100,000 MW.
27 . The preparation of claim 23 wherein said preparation is further devoid of caseinolytic hyaluronidase having molecular weight above approximately 45,000 MW.
28 . The preparation of claim 23 wherein said preparation is further devoid of gelatinolytic hyaluronidase having molecular weight between approximately 60,000-100,000 MW.
29 . The preparation of claim 23 wherein said preparation is a solution for injection having the following general formulation:
Hyaluronidase (ACS)
0-8000 I.U.;
Lactose, USP
13.3-133.3 mg; and
Phosphate, USP
5-200 mmoles;
and, wherein the hyaluronidase enzyme is devoid of molecular weight fractions below 40,000.
30 . The preparation of claim 29 wherein the amount of hyaluronidase (ACS) in said formulation is 7,200 I.U.
31 . The preparation of claim 29 wherein the components of said formulation are dissolved in balanced salt solution.Cited by (0)
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