Patent EP0204045A2 successfully refreshed from Google Patents.
EP0204045A2
Expired / Lapsed
EP
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Tableted blood plasma microconcentrated coagulation reagents and method of making same
Assignee: Bio Data Corp
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Filing: 1985-07-03
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Granted: —
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Expires: 2005-07-03
Abstract
Abstract @ A blood plasma coagulation reagent is prepared in microconcentrated tablet form by dry blending a binder and lubricant with a lyophilized active ingredient or ingredients and buffer, or dry blending a lubricant with a lyophilized active ingredient or ingredients and binder solution. In another related method a solution of the lyophilized active ingredient and binder is sprayed onto granules of lyophilized buffer. The dry blended mix is compacted, granulated and tableted. Two or more dry blended batches may be combined prior to compaction to increase the size of the final manufacturing batch.
Inventors
- 👤 Daniel E. Lawson
- 👤 Eugene J. Messa
- 👤 Michael Sokol
- 👤 Belinda S. Werner
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-29 08:30
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/20; A61K9/2095; C; C12; C12Q; C12Q1/00; C12Q1/56; G; G01; G01N; G01N2333/00; G01N2333/90; G01N2333/914; G01N2333/948; G01N2333/974
Claims Analysis
Total Claims: 66
Claim 1
Independent Claim
52 words
A tableting process for preparing microconcentrated blood plasma coagulation reagents comprising preparing a solution containing an active coagulation reagent, lyophilizing the solution to form a lyophilized reagent, adding a buffer, adding a binder, adding a lubricant, compacting the active reagent, buffer and binder, granulating the compacted material, and tableting the granulated material.
Claim 2
Dependent Claim
52 words
A tableting process for preparing microconcentrated blood plasma coagulation reagents comprising preparing a solution containing an active coagulation reagent, lyophilizing the solution to form a lyophilized reagent, adding a buffer, adding a binder, adding a lubricant, compacting the active reagent, buffer and binder, granulating the compacted material, and tableting the granulated material.
Claim 3
Dependent Claim
19 words
The process according to claim 1 wherein the binder is dry blended with the lyophilized reagent prior to compacting.
Claim 4
Dependent Claim
18 words
The process according to claim 1 wherein the binder is added to the reagent solution prior to lyophilization.
Claim 5
Dependent Claim
31 words
The process according to claim 1 wherein a disintegrating agent selected from the group consisting of celulose, starch and effervescent mixtures is added in an amount no greater than about 15.0%.
Claim 6
Dependent Claim
26 words
The process according to claim 1 wherein at least two dry blend batches are dry blended to form a manufacturing batch prior to the compacting step.
Claim 7
Dependent Claim
31 words
The process according to claim 1 wherein the coagulation reagent is thrombin and wherein a saline solution,a preservative or bovine serum albumin is added to the active reagent prior to lyophilization.
Claim 8
Dependent Claim
28 words
The process according to claim 1 wherein the active reagent is thrombin and wherein the buffer is HEPES buffer having a pH of about 6.2 to about 8.5.
Claim 9
Dependent Claim
50 words
The process according to claim 1 wherein the active reagent is thrombin, and wherein the binder is selected from the group consisting of about 97.0% sucrose and about 3.0% malto-dextrin, sucrose, maltose, mannitol and lactose, and wherein the binder is dry blended with the lyophilized active reagent prior to compacting.
Claim 10
Dependent Claim
135 words
The process according to claim 1 wherein the active reagent is thrombin selected from the group consisting of bovine thrombin and human thrombin havina a pH of about 6.5 to about 8.5, wherein the buffer is HEPES having a pH of about 6.2 to about 8.5 and a concentration of about 0.01M to about 0.6M, wherein a saline solution of about 0.85%, thimerosal in a concentration of about 0.02% and bovine serum albumin in a concentration of about 0.01% is added to the active reagent prior to lyophilization, wherein the binder is about 97.0% sucrose and about 3.0% malto-dextrin and is dry blended with the lyophilized reagent in an amount of about 20.0% to about 90.0% by weight, and wherein the lubricant is L-leucine in an amount of about 1.0% to about 12.0% by weight.
Claim 11
Dependent Claim
26 words
The process according to claim 1 wherein the active reagent is a thromboplastin, and wherein calcium chloride is added to the active reagent prior to lyophilization.
Claim 12
Dependent Claim
15 words
The process according to claim 10 wherein a divalent metal is added prior to compacting.
Claim 13
Dependent Claim
20 words
The process according to claim 11 wherein the divalent ion is selected from the group consisting of magnesium and manganese.
Claim 14
Dependent Claim
18 words
The process according to claim 10 wherein the binder is added to the active reagent prior to lyophilization.
Claim 15
Dependent Claim
17 words
The process according to claim 10 wherein the binder is dry blended with the lyophilized active reagent.
Claim 16
Dependent Claim
20 words
The process according to claim 10 wherein the buffer is selected from the group consisting of imidazole, tris and barbitol.
Claim 17
Dependent Claim
20 words
The process according to claim 10 including the step of adding a preservative to the active reagent prior to lyophilization.
Claim 18
Dependent Claim
23 words
The process according to claim 16 wherein the preservative is selected from the group consisting of thimerosal, neomycin sulfate, sodium azide and phenol.
Claim 19
Dependent Claim
29 words
The process according to claim 10 wherein the binder is selected from the group consisting of malto-dextrin, mannitol, and a mixture of about 97.0% sucrose and about 3.0% malto-dextrin.
Claim 20
Dependent Claim
24 words
The process according to claim 10 wherein the lubricant is selected from the group consisting of polyethylene glycol, magnesium stearate, L-leucine, glycine and silica.
Claim 21
Dependent Claim
67 words
The process according to claim 10 wherein the buffer is imidazole, wherein a divalent metal selected from the group consisting of magnesium and manganese is added, wherein the preservative is thimerosal, wherein about 1.0% to about 10.0% of malto-dextrin binder is added to the active reaqent prior lyophilization, and wherein about 1.0% to about 12.0% of polyethylene glycol lubricant is dry blended with the lyophilized active reagent.
Claim 22
Dependent Claim
28 words
The process according to claim 1 wherein the active reaqent is cephalin and a binder solution containing an activator is mixed with the reagent solution prior to lyophilization.
Claim 23
Dependent Claim
13 words
The process according to claim 21 wherein the activator is a particulate activator.
Claim 24
Dependent Claim
12 words
The process according to claim 22 wherein the activator is fumed silica.
Claim 25
Dependent Claim
18 words
The process according to claim 23 wherein the fumed silica has a size no greater than 0.012 microns.
Claim 26
Dependent Claim
21 words
The process according to claim 21 wherein the cephalin is mixed with a saline solution containing a preservative prior to lyophilization.
Claim 27
Dependent Claim
11 words
The process according to claim 25 wherein the preservative is thimerosal.
Claim 28
Dependent Claim
19 words
The process according to claim 21 wherein the buffer is tris, and the binder solution is a malto-dextrin solution.
Claim 29
Dependent Claim
38 words
The process according to claim 1 wherein the active reagent is a plasma control selected from the group consisting of fresh normal plasma drawn in CPDA-1, an abnormal control having less than normal clotting factors, and heparinized plasma.
Claim 30
Dependent Claim
35 words
The process according to claim 28 wherein the binder is a combination of a sugar selected from the group consisting of trehalose and sucrose, and a mixture of about 97.0% sucrose and about 3.0% malto-dextrin.
Claim 31
Dependent Claim
43 words
The process according to claim 29 wherein the sugar is an amount of about 0.5% by weight to about 20.0% by weight and the mixture of sucrose and malto-dextrin is in an amount of about 5.0% by weight to about 50.0% by weight.
Claim 32
Dependent Claim
33 words
The process according to claim 29 wherein the sugar is added to the active reagent prior to lyophilization and the mixture of sucrose and malto-dextrin is dry blended with the lyophilized active reagent.
Claim 33
Dependent Claim
28 words
The process according to claim 28 wherein the lubricant is dry blended with the lyophilized active reagent in an amount of about 1.0% to about 15.0% by weight.
Claim 34
Dependent Claim
21 words
The process according to claim 28 wherein the lubricant is selected from the group consisting of L-leucine, polyethylene glycol, and glycine.
Claim 35
Dependent Claim
20 words
The process according to claim 28 wherein the lubricant is no more than about 1% by weight of magnesium stearate.
Claim 36
Dependent Claim
25 words
The process according to claim 28 wherein up to about 5.0% by weight of a disintegrating agent is dry blended with the lyophilized active reagent.
Claim 37
Dependent Claim
94 words
The process according to claim 28 wherein a sugar selected from the group consisting of trehalose and sucrose in an amount of about 0.5% to 20.0% by weight is added to the active reagent prior to lyophilization, wherein a binder of about 97.0% sucrose and about 3.0% malto-dextrin is dry blended with the lyophilized active reagent in an amount from about 5.0% to about 50.0% by weight, and wherein the lubricant is polyethylene glycol which is dry blended with the lyophilized active reagent in an amount of about 1.0% to about 15.0% by weight.
Claim 38
Dependent Claim
25 words
The process according to claim 36 wherein up to about 5% by weight of a disintegrating agent is dry blended with the lyophilized active reagent.
Claim 39
Dependent Claim
42 words
The process according to claim 1 wherein the binder is added to the active reagent solution prior to lyophilization; the buffer is lyophilized, compacted and granulated; and the active reagent/binder solution is sprayed on the granulated buffer prior to the compacting step.
Claim 40
Dependent Claim
21 words
The process according to claim 38 wherein the lubricant is added after the granulating step and prior to the tabletinq step.
Claim 41
Dependent Claim
83 words
The process according to claim 38 wherein the active reagent is thromboplastin phospholipid which is dissolved in a calcium chloride solution, the binder is trehalose in an amount of about 1.0% to about 10.0% by weight, a divalent metal selected from the group consisting of magnesium and manganese is added to the buffer prior to lyophilization, the buffer is imidazole having a pH of about 7.35, and the lubricant is polyethylene glycol in an amount of about 1.0% to about 12.0% by weight.
Claim 42
Dependent Claim
56 words
A microconcentrated blood plasma coagulation reagent tablet comprising an active reagent selected from the group consisting of thrombin, thromboplastin, cephalin, fresh normal plasma drawn in CPDA-1, abnormal plasma having less than normal clotting factors, and heparinized plasma; a buffer selected from the group consisting of HEPES, imidazole, tris, glycine, and barbitol; a binder; and a lubricant.
Claim 43
Dependent Claim
56 words
A microconcentrated blood plasma coagulation reagent tablet comprising an active reagent selected from the group consisting of thrombin, thromboplastin, cephalin, fresh normal plasma drawn in CPDA-1, abnormal plasma having less than normal clotting factors, and heparinized plasma; a buffer selected from the group consisting of HEPES, imidazole, tris, glycine, and barbitol; a binder; and a lubricant.
Claim 44
Dependent Claim
42 words
The tablet according to claim 41 wherein the active reagent is lyophilized thrombin, the binder is in an. amount from about 20.0% to about 90.0% by weight, and the lubricant is in an amount from about 1.0% to about 12.0% by weight.
Claim 45
Dependent Claim
28 words
The tablet according to claim 42 wherein the binder is selected from the group consisting of about 97.0% sucrose and about 3.0% malto-dextrin, sucrose, maltose, mannitol and lactose.
Claim 46
Dependent Claim
23 words
The tablet according to claim 42 wherein the lubricant is selected from the group consisting of L-leucine, polyethylene glycol, magnesium stearate and talc.
Claim 47
Dependent Claim
25 words
The tablet according to claim 42 including sodium chloride, a preservative selected from the group consisting of thimerosal and sodium azide, and bovine serum albumin.
Claim 48
Dependent Claim
19 words
The tablet according to claim 41 wherein the active reagent is lyophilized thromboplastin and the tablet includes calcium chloride.
Claim 49
Dependent Claim
20 words
The tablet according to claim 46 wherein the buffer is selected from the group consisting of imidazole, tris, and barbitol.
Claim 50
Dependent Claim
13 words
The tablet according to claim 46 including a divalent metal other than calcium.
Claim 51
Dependent Claim
20 words
The tablet according to claim 48 wherein the divalent metal is selected from the group consisting of magnesium and manganese.
Claim 52
Dependent Claim
22 words
The tablet according to claim 46 including a preservative selected from the group consisting of thimerosal, neomycin sulfate, sodium azide, and phenol.
Claim 53
Dependent Claim
22 words
The tablet according to claim 46 wherein the binder is malto-dextrin in an amount from about 1% to about 10.0% by weight.
Claim 54
Dependent Claim
21 words
The tablet according to claim 46 wherein the lubricant is polyethylene glycol in an amount from about 1.0% to about 12.0%.
Claim 55
Dependent Claim
24 words
The tablet according to claim 46 wherein the lubricant is selected from the group consisting of polyethylene glycol, magnesium stearate, L-leucine, glycine and silica.
Claim 56
Dependent Claim
18 words
The tablet according to claim 41 wherein the active reagent is cephalin and the binder contains an activator.
Claim 57
Dependent Claim
12 words
The tablet according to claim 54 wherein the activator is fumed silica.
Claim 58
Dependent Claim
13 words
The tablet according to claim 54 wherein the activator is a particulate activator.
Claim 59
Dependent Claim
18 words
The tablet according to claim 54 wherein the fumed silica is no greater than 0.012 microns in size.
Claim 60
Dependent Claim
25 words
The tablet according to claim 54 wherein the buffer is tris, the binder is malto-dextrin containing fumed silica, and the tablet contains saline and thimerosal.
Claim 61
Dependent Claim
68 words
The tablet according to claim 41 wherein the active reagent is selected from the group consisting of fresh normal plasma drawn in CPDA-1, abnormal plasma having less than normal clotting factors and a heparinized plasma, wherein the binder is a sugar in an amount from about 5.0% to about 50.0% by weight, and wherein the lubricant is in an amount of about 1.0% to about 15.0% by weight.
Claim 62
Dependent Claim
32 words
The tablet according to claim 59 wherein the binder is a combination of a sugar selected from the group consisting of sucrose and trehalose and about 97.0% sucrose and about 3.0% malto-dextrin.
Claim 63
Dependent Claim
21 words
The tablet according to claim 59 wherein the lubricant is selected from the group consisting of L-leucine, polyethylene glycol, and glycine.
Claim 64
Dependent Claim
20 words
The tablet according to claim 59 wherein the tablet includes a disintegrating agent in an amount up to about 5%.
Claim 65
Dependent Claim
22 words
The tablet according to claim 62 wherein the disintegrating agent is selected from the group consisting of cellulose, starch and effervescent mixtures.
Claim 66
Dependent Claim
12 words
The tablet according to claim 59 wherein the lubricant is polyethylene glycol.
References Cited (Backward Citations)
No citation records indexed.
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