US5585007A
Expired / Lapsed
US
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Plasma concentrate and tissue sealant methods and apparatuses for making concentrated plasma and/or tissue sealant
Assignee: PlasmaSeal LLC
•
Filing: 1994-12-07
•
Granted: 1996-12-17
•
Expires: 2014-12-07
Abstract
Abstract An inexpensive device with a disposable cartridge for preparing tissue sealant is disclosed. The device is particularly applicable to star preparation of autologous tissue sealant. A method of sealing tissue in which the tissue sealant is applied immediately after mixing platelet-rich plasma concentrate (from the device) with a solution of calcium and thrombin is also disclosed. Preparation in the operating room of 5 cc sealant from 50 cc patient blood requires less than 15 minutes and only one simple operator step. There is no risk of tracking error because processing can be done in the operating room. Chemicals added may be limited to anticoagulant (e.g., citrate) and calcium chloride. The disposable cartridge may fit in the palm of the hand and is hermetically sealed to eliminate possible exposure to patient blood and ensure sterility. Adhesive and tensile strengths are comparable or superior to pooled blood fibrin sealants made with precipitation methods. Antifibrinolytic agents (such as aprotinin) are not necessary because the tissue sealant contains high concentrations of natural inhibitors of fibrinolysis from the patient's blood. The tissue sealant also contains patient platelets and additional factors not present in available fibrin sealants that promote wound healing.
Inventors
- 👤 Richard D. Antanavich
- 👤 Randel Dorian
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 06:01
CPC Classifications
B; B01; B01D; B01D67/00; B01D67/0081; B01D67/0093; B01D67/00933; A; A61; A61L; A61L24/00; A61L24/04; A61L24/10; A61L24/106; A61M; A61M1/00; A61M1/36; A61M1/3693; B01D61/00; B01D61/14; B01D61/18; B01D63/00; B01D63/16; B04; B04B; B04B5/00; B04B5/04; B04B5/0442; B01D2323/00; B01D2323/30; B04B2005/0478
Claims Analysis
Total Claims: 51
Claim 1
Independent Claim
57 words
A method of making concentrated plasma for use as a tissue sealant or adhesive, comprising the steps of: (a) separating plasma from whole blood; (b) removing water from said plasma by contacting said plasma with a concentrator which does not significantly denature fibrinogen to provide said concentrated plasma; and (c) separating said concentrated plasma from said concentrator.
Claim 2
Independent Claim
57 words
A method of making concentrated plasma for use as a tissue sealant or adhesive, comprising the steps of: (a) separating plasma from whole blood; (b) removing water from said plasma by contacting said plasma with a concentrator which does not significantly denature fibrinogen to provide said concentrated plasma; and (c) separating said concentrated plasma from said concentrator.
Claim 3
Dependent Claim
60 words
The method of claim 1, wherein said separating step (a) comprises centrifugally contacting said whole blood with a separator which bars passage of red blood cells and white blood cells in the absence of an applied centrifugal force, and applying a centrifugal force effective to pass red blood cells and white blood cells in said whole blood through said separator.
Claim 4
Dependent Claim
16 words
The method of claim 2, wherein said separator is a mat, foam or porous plastic annulus.
Claim 5
Dependent Claim
47 words
The method of claim 1, wherein said separating step (a) comprises centrifugally settling said whole blood into a chamber shaped and positioned such that gravity does not permit drainage of said red blood cells and said white blood cells in the absence of an applied centrifugal force.
Claim 6
Dependent Claim
31 words
The method of claim 1, wherein each of said whole blood and said plasma contains (i) platelets, (ii) high molecular weight compounds or (iii) both platelets and high molecular weight compounds.
Claim 7
Dependent Claim
11 words
A platelet-rich plasma concentrate, prepared by the process of claim 5.
Claim 8
Dependent Claim
41 words
The method of claim 1, wherein said concentrator comprises a material selected from the group consisting of a dextranomer, dextramine, polyacrylamide, silica gel, a zeolite, cross-linked agarose, starch and alginate gel, either in free bead form or attached to a surface.
Claim 9
Dependent Claim
24 words
The method of claim 7, wherein said material is attached to a matrix, and said matrix comprises a mat, a foam or a disc.
Claim 10
Dependent Claim
25 words
The method of claim 1, wherein said blood contains an amount of an added coagulation inhibitor which is effective to inhibit coagulation of said blood.
Claim 11
Dependent Claim
54 words
The method of claim 1, conducted in a sealed cartridge having an inlet, a first chamber containing a first separator for separating said plasma from said whole blood, a second chamber containing said concentrator and a second separator for separating said concentrated plasma from said concentrator, and an outlet for withdrawing said concentrated plasma.
Claim 12
Dependent Claim
22 words
The method of claim 1, further comprising, after said separating step (c), repeating said contacting step (b) and said separating step (c).
Claim 13
Dependent Claim
10 words
A plasma concentrate, prepared by the process of claim 1.
Claim 14
Dependent Claim
12 words
The plasma concentrate of claim 12, wherein said plasma concentrate is autologous.
Claim 15
Dependent Claim
13 words
A tissue sealant, comprising the plasma concentrate of claim 12 and an activator.
Claim 16
Dependent Claim
27 words
The tissue sealant of claim 14, wherein said activator is a mixture of thrombin and calcium in amounts sufficient to permit gelation of said platelet-rich plasma concentrate.
Claim 17
Dependent Claim
14 words
The tissue sealant of claim 14, wherein said activator is autologous thrombin and platelets.
Claim 18
Dependent Claim
45 words
A method of sealing tissue, comprising the steps of: (a) preparing a plasma concentrate according to the process of claim 1, (b) activating said plasma concentrate to provide an activated plasma concentrate, and (c) applying said activated plasma concentrate to tissue in need of sealing.
Claim 19
Dependent Claim
30 words
The method of claim 17, wherein said plasma concentrate is obtained from blood drawn from a patient, and said tissue in need of sealing is in or on said patient.
Claim 20
Dependent Claim
29 words
The method of claim 17, wherein said activating comprises contacting said plasma concentrate with a mixture of thrombin and calcium in amounts sufficient to gel said activated plasma concentrate.
Claim 21
Dependent Claim
64 words
A method of sealing tissue, comprising the steps of: (a) preparing a plasma concentrate according to the process of claim 1, said plasma concentrate containing prothrombin, platelets or both prothrombin and platelets, (b) activating said prothrombin, said platelets or both said prothrombin and said platelets to provide an activated plasma concentrate, and (c) applying said activated plasma concentrate to tissue in need of sealing.
Claim 22
Dependent Claim
24 words
The method of claim 20, wherein said activating comprises irradiating said platelets with ultrasound sufficiently to result in gelation of said activated plasma concentrate.
Claim 23
Dependent Claim
23 words
The method of claim 20, wherein said activating comprises heating said plasma concentrate sufficiently to result in gelation of said activated plasma concentrate.
Claim 24
Dependent Claim
19 words
The apparatus of claim 21, wherein said concentrator has a molecular weight cutoff of from 2 to 100 kDa.
Claim 25
Dependent Claim
39 words
The apparatus of claim 21, wherein said concentrator is selected from the group consisting of a dextranomer, dextramine, polyacrylamide, silica gel, a zeolite, cross-linked agarose, starch and alginate gel, either in free bead form or attached to a surface.
Claim 26
Dependent Claim
16 words
The apparatus of claim 21, wherein said concentrator is embedded in or attached to a surface.
Claim 27
Dependent Claim
13 words
The apparatus of claim 25, wherein said matrix comprises a plurality of discs.
Claim 28
Dependent Claim
48 words
A plasma concentrate comprising platelets, from 5 to 400 mg/ml of fibrinogen, from 0.5 to 35 mg/ml of fibronectin, and a physiologically acceptable carrier comprising water and physiologically acceptable inorganic and organic ions in a physiological acceptable concentration, wherein the fibrinogen in the concentrate is not significantly denatured.
Claim 29
Dependent Claim
48 words
A plasma concentrate comprising platelets, from 5 to 400 mg/ml of fibrinogen, from 0.5 to 35 mg/ml of fibronectin, and a physiologically acceptable carrier comprising water and physiologically acceptable inorganic and organic ions in a physiological acceptable concentration, wherein the fibrinogen in the concentrate is not significantly denatured.
Claim 30
Dependent Claim
39 words
The plasma concentrate of claim 27, prepared from whole blood, wherein said platelets are present in said plasma concentrate in a concentration of at least one-and-one-half times the concentration of said platelets in unconcentrated plasma from said whole blood.
Claim 31
Dependent Claim
45 words
The plasma concentrate of claim 27, further containing a compound selected from the group consisting of an antibiotic, a collagen fleece, collagenase, hyaluronic acid, a wound-healing factor, zinc ions in an amount effective to decrease coagulation time of said plasma, and a biologically acceptable dye.
Claim 32
Dependent Claim
25 words
The plasma concentrate of claim 29, further containing disulphine blue in an amount sufficient to visibly detect said plasma concentrate during its application to tissue.
Claim 33
Dependent Claim
12 words
The plasma concentrate of claim 27, further comprising a pharmaceutically active compound.
Claim 34
Independent Claim
45 words
A method of making concentrated plasma for use as a tissue sealant or adhesive, comprising the steps of: (a) separating plasma from whole blood; and (b) removing water from said plasma with a concentrator which does not significantly denature fibrinogen to provide said concentrated plasma.
Claim 35
Independent Claim
45 words
A method of making concentrated plasma for use as a tissue sealant or adhesive, comprising the steps of: (a) separating plasma from whole blood; and (b) removing water from said plasma with a concentrator which does not significantly denature fibrinogen to provide said concentrated plasma.
Claim 36
Dependent Claim
11 words
A method of claim 32 wherein the concentrator is a water-absorbent.
Claim 37
Dependent Claim
31 words
A method of claim 33 wherein the concentrator is a material selected from the group consisting of a dextranomer dextramine, polyacrylamide, silica gel, a zeolite, cross-linked agarose, starch and alginate gel.
Claim 38
Independent Claim
18 words
A method of claims 34 wherein the concentrator is a free bead form or attached to a surface.
Claim 39
Dependent Claim
11 words
A method of claim 32 wherein the concentrator includes a membrane.
Claim 40
Independent Claim
53 words
An apparatus with a disposable cartridge for concentrating plasma for use as a tissue sealant or adhesive, comprising a centrifuge separator means for separating plasma from whole blood; and concentrator means in fluid communication with said centrifuge separator means for removing water from said plasma without significantly denaturing fibrinogen, to provide concentrated plasma.
Claim 41
Independent Claim
53 words
An apparatus with a disposable cartridge for concentrating plasma for use as a tissue sealant or adhesive, comprising a centrifuge separator means for separating plasma from whole blood; and concentrator means in fluid communication with said centrifuge separator means for removing water from said plasma without significantly denaturing fibrinogen, to provide concentrated plasma.
Claim 42
Dependent Claim
62 words
An apparatus of claim 37 comprising a first chamber containing the centrifuge separator for separating plasma from whole blood; and a second chamber in fluid communication with said first chamber, the second chamber including a concentrator means for concentrating said plasma by removing water from said plasma without significantly denaturing fibrinogen and a second separator for separating concentrated plasma from said concentrator.
Claim 43
Dependent Claim
32 words
An apparatus of claim 38 wherein the concentrator means comprises a material selected from the group consisting of a dextranomer, dextramine, polyacrylamide, silica gel, a zeolite, cross-linked agarose, starch and alginate gel.
Claim 44
Dependent Claim
19 words
An apparatus of claim 39 wherein the concentrator means is a free bead form or attached to a surface.
Claim 45
Dependent Claim
12 words
An apparatus of claim 38 wherein the concentrator means includes a membrane.
Claim 46
Dependent Claim
22 words
A plasma concentrate containing fibrinogen for use as a tissue sealant or adhesive, the fibrinogen in said concentrate not being significantly denatured.
Claim 47
Dependent Claim
22 words
A plasma concentrate containing fibrinogen for use as a tissue sealant or adhesive, the fibrinogen in said concentrate not being significantly denatured.
Claim 48
Dependent Claim
14 words
A plasma concentrate of claim 42 containing from 5 to 400 mg/ml of fibrinogen.
Claim 49
Dependent Claim
10 words
A plasma concentrate made by the process of claim 38.
Claim 50
Independent Claim
91 words
An apparatus with a disposable cartridge for concentrating plasma for use as a tissue sealant or adhesive, comprising: an inlet, a first chamber in fluid communication with said inlet, the first chamber containing a centrifuge separator for separating plasma from whole blood, a second chamber in fluid communication with said first chamber, the second chamber containing a concentrator for concentrating said plasma by removing water from said plasma without significantly denaturing fibrinogen and a second separator for separating concentrated plasma from said concentrator, and an outlet for withdrawing said concentrated plasma.
Claim 51
Independent Claim
91 words
An apparatus with a disposable cartridge for concentrating plasma for use as a tissue sealant or adhesive, comprising: an inlet, a first chamber in fluid communication with said inlet, the first chamber containing a centrifuge separator for separating plasma from whole blood, a second chamber in fluid communication with said first chamber, the second chamber containing a concentrator for concentrating said plasma by removing water from said plasma without significantly denaturing fibrinogen and a second separator for separating concentrated plasma from said concentrator, and an outlet for withdrawing said concentrated plasma.
References Cited (Backward Citations)
DE56103C
Cited
US2553004A
Cited
GB854715A
Cited
DE1443359A1
Cited
US3453364A
Cited
US4225580B1
Cited
US4225580A
Cited
US4537767A
Cited
US4059108A
Cited
US4204537A
Cited
US3972812A
Cited
US5217426A
Cited
US4303193A
Cited
US4362567A
Cited
US4377572A
Cited
US4298598A
Cited
US4294707A
Cited
US4300717A
Cited
US4770779A
Cited
US4453939A
Cited
US4427650A
Cited
US4442655A
Cited
US4427651A
Cited
US4735726A
Cited
US4650678A
Cited
EP0090997A2
Cited
EP0102773A2
Cited
EP0109374A1
Cited
US5376263A
Cited
US4632761A
Cited
US4755301A
Cited
US4672969A
Cited
US4631055A
Cited
US4655211A
Cited
US4928603A
Cited
US4627879A
Cited
US4639316A
Cited
US4735616A
Cited
US5141645A
Cited
US5071570A
Cited
EP0253198B1
Cited
US4943273A
Cited
US4983158A
Cited
US4714457A
Cited
WO1988002259A1
Cited
US4818291A
Cited
US5370802A
Cited
US5322620A
Cited
US4832851A
Cited
US4983157A
Cited
US4879031A
Cited
US5260420A
Cited
US5290552A
Cited
US4985153A
Cited
US4874368A
Cited
US4902281A
Cited
US5002571A
Cited
US5190759A
Cited
WO1990010031A1
Cited
US5405607A
Cited
US5226877A
Cited
US5000970A
Cited
US5152905A
Cited
US5258126A
Cited
US5316674A
Cited
US5030215A
Cited
US5219328A
Cited
US5321126A
Cited
US5185001A
Cited
US5045048A
Cited
US5204537A
Cited
US5420250A
Cited
US5173295A
Cited
US5279825A
Cited
US5112484A
Cited
US5100564A
Cited
US5217627A
Cited
US5137832A
Cited
US5206023A
Cited
US5156613A
Cited
WO1992022312A1
Cited
US5304372A
Cited
US5298171A
Cited
BR9103724A
Cited
WO1993005067A1
Cited
US5281342A
Cited
EP0534178A2
Cited
US5190057A
Cited
US5417650A
Cited
US5403272A
Cited
US5443481A
Cited
US5456693A
Cited
EP0592242A1
Cited
CN1074709A
Cited
US5395923A
Cited
US5290918A
Cited
US5330974A
Cited
US5411885A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1999-12-17 | 2000-06-17 | 2000-12-17 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2003-12-17 | 2004-06-17 | 2004-12-17 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2007-12-17 | 2008-06-17 | 2008-12-17 | $7700.00 | Window Closed / Lapsed |