US5045529A
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US
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Tonometric fluid for blood gas and co-oximetry instruments
Assignee: FERRARIS GROUP Inc
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Filing: 1989-03-27
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Granted: 1991-09-03
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Expires: 2009-03-27
Abstract
Abstract A stable reference solution for calibrating and monitoring blood gas instrumentation is disclosed. The solution comprises an aqueous mixture containing a hemoglobin solution derived from a mammalian source which comprises at least about 95% reduced hemoglobin. The solution additionally contains a bicarbonate buffer and a metal catalyzed methemoglobin reducing system and an organic buffer. To provide a control element having a variety of properties similar to fresh, whole, human blood, the reference solution is stored in a sealed ampule under an inert atmosphere containing CO2 until just prior to use. The ampule is subsequently opened and the solution is equilibrated with a gas mixture having components which provide gasses in a physiological range to the solution. The solution is characterized by exhibiting properties similar to fresh blood subsequent to equilibration and an extended storage life prior to equilibration.
Inventors
- 👤 Ching Chiang
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-04 10:08
CPC Classifications
G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/96; G01N2333/00; G01N2333/795; G01N2333/805; G01N2496/00; G01N2496/70; Y; Y10; Y10T; Y10T436/00; Y10T436/10; Y10T436/102499; Y10T436/105831; Y10T436/106664; Y10T436/108331
Claims Analysis
Total Claims: 57
Claim 1
Independent Claim
82 words
A stable reference solution which comprises an aqueous mixture containing: a) a hemoglobin solution comprising fractions of: i) at least about 95% reduced hemoglobin, ii) less than about 3% methemoglobin, iii) less than about 2% carboxyhemoglobin, iv) less than about 2% oxyhemoglobin, and v) less than about 0.3% by volume oxygen; b) a source of bicarbonate ions; c) a source of thio functional groups; d) a source of metal ion catalyst; e) at least one organic polyphosphate; and, f) an organic buffer.
Claim 2
Dependent Claim
82 words
A stable reference solution which comprises an aqueous mixture containing: a) a hemoglobin solution comprising fractions of: i) at least about 95% reduced hemoglobin, ii) less than about 3% methemoglobin, iii) less than about 2% carboxyhemoglobin, iv) less than about 2% oxyhemoglobin, and v) less than about 0.3% by volume oxygen; b) a source of bicarbonate ions; c) a source of thio functional groups; d) a source of metal ion catalyst; e) at least one organic polyphosphate; and, f) an organic buffer.
Claim 3
Dependent Claim
13 words
A stable reference solution as in claim 1 additionally including an antimicrobial agent.
Claim 4
Dependent Claim
16 words
A stable reference solution as in claim 1 additionally including a red blood cell lysing agent.
Claim 5
Dependent Claim
44 words
A stable reference solution as in claim 1 having a P 50 value of between about 18 to about 34 mmHg, with a nominal value of 26 after tonometry with an appropriate gas mixture of O 2 , CO 2 and N 2 .
Claim 6
Dependent Claim
14 words
A stable reference solution as in claim 1 wherein the hemoglobin is mammalian hemoglobin.
Claim 7
Dependent Claim
14 words
A stable reference solution as in claim 5 wherein the hemoglobin is bovine hemoglobin.
Claim 8
Dependent Claim
16 words
A stable reference solution as in claim 1 wherein the bicarbonate ion source comprises sodium bicarbonate.
Claim 9
Dependent Claim
21 words
A stable reference solution as in claim 1 wherein the thio functional groups are provided by at least one sulfhydro compound.
Claim 10
Dependent Claim
20 words
A stable reference solution as in claim 8 wherein the sulfhydro compound comprises reduced glutathione, mercaptoethanol, cysteine or derivatives thereof.
Claim 11
Dependent Claim
30 words
A stable reference solution as in claim 1 herein the source of metal ion catalyst comprises a salt of metals selected from the group consisting of selenium, tellurium and copper.
Claim 12
Dependent Claim
31 words
A stable reference solution as in claim 10 wherein sad source of metal ion catalyst is selected from the group consisting of sodium selenite, sodium tellurite, cupric chloride and derivatives thereof.
Claim 13
Dependent Claim
21 words
A stable reference solution as in claim 2 wherein the antimicrobial agent comprises an aqueous solution of 2-phenoxyethanol and benzethonium chloride.
Claim 14
Dependent Claim
18 words
A stable reference solution as in claim 3 wherein the red blood cell lysing agent comprises benzethonium chloride.
Claim 15
Dependent Claim
26 words
A stable reference solution as in claim 1 wherein the organic polyphosphate compound is selected from the group consisting of 2,3-diphosphoglycerate, phytic acid and adenosine triphosphate.
Claim 16
Dependent Claim
25 words
A stable reference solution as in claim 1 wherein the organic buffer is selected from the group consisting of HEPES, DIPSO, POPSO, TAPSO and HEPPSO.
Claim 17
Dependent Claim
13 words
A stable reference solution as in claim 1 contained within a sealed container.
Claim 18
Dependent Claim
29 words
A stable reference solution as in claim 16 wherein the sealed container has a head space containing CO 2 and a gas which is inert to the reference solution.
Claim 19
Dependent Claim
37 words
A stable reference solution as in claim 17 wherein at least about 93% of the gas contained in the head space is an inert gas selected from the group consisting of nitrogen, noble gasses and mixtures thereof.
Claim 20
Dependent Claim
154 words
A stable reference solution for tonometry instrumentation which comprises an aqueous mixture containing: a) between about 13 and about 15 g/dl bovine hemoglobin solution, said hemoglobin solution comprising fractions of: i) at least about 95% reduced hemoglobin; ii) less than about 3% methemoglobin; iii) less than about 2% carboxyhemoglobin; iv) less than about 2% oxyhemoglobin; and v) less than about 0.3% by volume oxygen; b) between about 0.09 and about 0.11 g/dl 2-phenoxyethanol; c) between about 0.09 and about 0.11 g/dl benzethonium chloride; d) a concentration of sodium selenite ranging from about 1.0 to about 20 μM; e) a concentration of phytic acid ranging from about 0.1 to about 1.4 mM; f) a concentration of reduced glutathione ranging from about 0.5 to about 8 mM; g) a concentration of sodium bicarbonate ranging from about 28.5 to about 30.5 mM; and h) a concentration of HEPES buffer ranging from about 20 to about 40 mM.
Claim 21
Dependent Claim
154 words
A stable reference solution for tonometry instrumentation which comprises an aqueous mixture containing: a) between about 13 and about 15 g/dl bovine hemoglobin solution, said hemoglobin solution comprising fractions of: i) at least about 95% reduced hemoglobin; ii) less than about 3% methemoglobin; iii) less than about 2% carboxyhemoglobin; iv) less than about 2% oxyhemoglobin; and v) less than about 0.3% by volume oxygen; b) between about 0.09 and about 0.11 g/dl 2-phenoxyethanol; c) between about 0.09 and about 0.11 g/dl benzethonium chloride; d) a concentration of sodium selenite ranging from about 1.0 to about 20 μM; e) a concentration of phytic acid ranging from about 0.1 to about 1.4 mM; f) a concentration of reduced glutathione ranging from about 0.5 to about 8 mM; g) a concentration of sodium bicarbonate ranging from about 28.5 to about 30.5 mM; and h) a concentration of HEPES buffer ranging from about 20 to about 40 mM.
Claim 22
Dependent Claim
44 words
A stable reference solution as in claim 19 having a P 50 value of between about 18 to about 34 mmHg, with a nominal value of 26 after tonometry with an appropriate gas mixture of O 2 , CO 2 and N 2 .
Claim 23
Dependent Claim
16 words
A stable reference solution as in claim 19 which contains about 14 g/dl bovine hemoglobin solution.
Claim 24
Dependent Claim
14 words
A stable reference solution as in claim 19 which contains about 0.1 g/dl 2-phenoxyethanol.
Claim 25
Dependent Claim
15 words
A stable reference solution as in claim 19 which contains about 0.1 g/dl benzethonium chloride.
Claim 26
Dependent Claim
18 words
A stable reference solution as in claim 19 wherein the concentration of sodium selenite is about 2 μM.
Claim 27
Dependent Claim
18 words
A stable reference solution as in claim 19 wherein the concentration of phytic acid is about 0.14 mM.
Claim 28
Dependent Claim
18 words
A stable reference solution as in claim 19 wherein the concentration of reduced glutathione is about 0.8 mM.
Claim 29
Dependent Claim
18 words
A stable reference solution as in claim 19 wherein the concentration of sodium bicarbonate is about 29.16 mM.
Claim 30
Dependent Claim
17 words
A stable reference solution as in claim 19 wherein the concentration of HEPES is about 25 mM.
Claim 31
Dependent Claim
47 words
A stable reference as in claim 19 contained within a sealed container, said container having a head space containing at least about 93% inert gas selected from the group consisting of nitrogen, noble gasses and mixtures thereof, and the remainder of the gas comprising CO 2 .
Claim 32
Dependent Claim
154 words
A stable reference solution for tonometry instrumentation which comprises an aqueous mixture containing: a) between about 8 and about 10 g/dl bovine hemoglobin solution, said hemoglobin solution comprising fractions of: i) at least about 95% reduced hemoglobin, ii) less than about 3% methemoglobin, iii) less than about 2% carboxyhemoglobin, iv) less than about 2% oxyhemoglobin, and v) less than about 0.3% by volume oxygen; b) between about 0.09 and about 0.11 g/dl 2-phenoxyethanol; c) between about 0.09 and about 0.11 g/dl benzethonium chloride; d) a concentration of sodium selenite ranging from about 1 to about 20 μM; e) a concentration of phytic acid ranging from about 0.1 to about 1.4 mM; f) a concentration of reduced glutathione ranging from about 0.5 to about 8 mM; g) a concentration of sodium bicarbonate ranging from about 19.5 to about 21.5 mM; and h) a concentration of HEPES buffer ranging from about 20 to about 40 mM.
Claim 33
Dependent Claim
154 words
A stable reference solution for tonometry instrumentation which comprises an aqueous mixture containing: a) between about 8 and about 10 g/dl bovine hemoglobin solution, said hemoglobin solution comprising fractions of: i) at least about 95% reduced hemoglobin, ii) less than about 3% methemoglobin, iii) less than about 2% carboxyhemoglobin, iv) less than about 2% oxyhemoglobin, and v) less than about 0.3% by volume oxygen; b) between about 0.09 and about 0.11 g/dl 2-phenoxyethanol; c) between about 0.09 and about 0.11 g/dl benzethonium chloride; d) a concentration of sodium selenite ranging from about 1 to about 20 μM; e) a concentration of phytic acid ranging from about 0.1 to about 1.4 mM; f) a concentration of reduced glutathione ranging from about 0.5 to about 8 mM; g) a concentration of sodium bicarbonate ranging from about 19.5 to about 21.5 mM; and h) a concentration of HEPES buffer ranging from about 20 to about 40 mM.
Claim 34
Dependent Claim
43 words
A stable reference solution as in claim 30 having a P 50 value of about 18 to about 34 mmHg, with a nominal value of 26 after tonometry with an appropriate gas mixture of O 2 , CO 2 and N 2 .
Claim 35
Dependent Claim
16 words
A stable reference solution as in claim 30 which contains about 9 g/dl bovine hemoglobin solution.
Claim 36
Dependent Claim
14 words
A stable reference solution as in claim 30 which contains about 0.1 g/dl 2-phenoxyethanol.
Claim 37
Dependent Claim
15 words
A stable reference solution as in claim 30 which contains about 0.1 g/dl benzethonium chloride.
Claim 38
Dependent Claim
18 words
A stable reference solution as in claim 30 wherein the concentration of sodium selenite is about 2 μM.
Claim 39
Dependent Claim
18 words
A stable reference solution as in claim 30 wherein the concentration of phytic acid is about 0.14 mM.
Claim 40
Dependent Claim
18 words
A stable reference solution as in claim 30 wherein the concentration of reduced glutathione is about 0.8 mM.
Claim 41
Dependent Claim
18 words
A stable reference solution as in claim 30 wherein the concentration of sodium bicarbonate is about 20.5 mM.
Claim 42
Dependent Claim
17 words
A stable reference solution as in claim 30 wherein the concentration of HEPES is about 25 mM.
Claim 43
Dependent Claim
48 words
A stable reference solution as in claim 30 contained within a sealed container, said container having a head space containing at least about 93% inert gas selected from the group consisting of nitrogen, noble gasses and mixtures thereof, and the remainder of the gas comprising CO 2 .
Claim 44
Dependent Claim
153 words
A stable reference solution for tonometry instrumentation which comprises an aqueous mixture containing: a) between about 17 and about 19 g/dl bovine hemoglobin solution, said hemoglobin solution comprising fractions of: i) at least about 95% reduced hemoglobin; ii) less than about 3% methemoglobin; iii) less than about 2% carboxyhemoglobin; iv) less than about 2% oxyhemoglobin; v) less than about 0.3% by volume oxygen; b) between about 0.09 and about 0.11 g/dl 2-phenoxyethanol; c) between about 0.09 and about 0.11 g/dl benzethonium chloride; d) a concentration of sodium selenite ranging from about 1 to about 20 μM; e) a concentration of phytic acid ranging from about 0.1 to about 1.4 mM; f) a concentration of reduced glutathione ranging from about 0.5 to about 8 mM; g) a concentration of sodium bicarbonate ranging from about 19 to about 21 mM; and h) a concentration of HEPPSO buffer ranging from about 20 to about 40 mM.
Claim 45
Dependent Claim
153 words
A stable reference solution for tonometry instrumentation which comprises an aqueous mixture containing: a) between about 17 and about 19 g/dl bovine hemoglobin solution, said hemoglobin solution comprising fractions of: i) at least about 95% reduced hemoglobin; ii) less than about 3% methemoglobin; iii) less than about 2% carboxyhemoglobin; iv) less than about 2% oxyhemoglobin; v) less than about 0.3% by volume oxygen; b) between about 0.09 and about 0.11 g/dl 2-phenoxyethanol; c) between about 0.09 and about 0.11 g/dl benzethonium chloride; d) a concentration of sodium selenite ranging from about 1 to about 20 μM; e) a concentration of phytic acid ranging from about 0.1 to about 1.4 mM; f) a concentration of reduced glutathione ranging from about 0.5 to about 8 mM; g) a concentration of sodium bicarbonate ranging from about 19 to about 21 mM; and h) a concentration of HEPPSO buffer ranging from about 20 to about 40 mM.
Claim 46
Dependent Claim
43 words
A stable reference solution as in claim 41 having a P 50 value of about 18 to about 34 mmHg, with a nominal value of 26 after tonometry with an appropriate gas mixture of O 2 , CO 2 and N 2 .
Claim 47
Dependent Claim
16 words
A stable reference solution as in claim 41 which contains about 18 g/dl bovine hemoglobin solution.
Claim 48
Dependent Claim
14 words
A stable reference solution as in claim 41 which contains about 0.1 g/dl 2-phenoxyethanol.
Claim 49
Dependent Claim
15 words
A stable reference solution as in claim 41 which contains about 0.1 g/dl benzethonium chloride.
Claim 50
Dependent Claim
18 words
A stable reference solution as in claim 41 wherein the concentration of sodium selenite is about 2 μM.
Claim 51
Dependent Claim
18 words
A stable reference solution as in claim 41 wherein the concentration of phytic acid is about 0.14 mM.
Claim 52
Dependent Claim
18 words
A stable reference solution as in claim 41 wherein the concentration of reduced glutathione is about 0.8 mM.
Claim 53
Dependent Claim
18 words
A stable reference solution as in claim 41 wherein the concentration of sodium bicarbonate is about 19.8 mM.
Claim 54
Dependent Claim
17 words
A stable reference solution as in claim 41 wherein the concentration of HEPPSO is about 25 mM.
Claim 55
Dependent Claim
48 words
A stable reference solution as in claim 41 contained within a sealed container, said container having a head space containing at least about 93% inert gas selected from the group consisting of nitrogen, noble gasses and mixtures thereof, and the remainder of the gas comprising CO 2 .
Claim 56
Independent Claim
187 words
A method for providing a reference standard for blood gas and CO-Oximetry instrumentation comprising the steps of: 1) providing a stable reference solution which comprises an aqueous mixture containing: a) a hemoglobin solution comprising fractions of: i) at least about 95% reduced hemoglobin, ii) less than about 3% methemoglobin, iii) less than about 2% carboxyhemoglobin, iv) less than 2% oxyhemoglobin, and v) less than about 0.3% by volume oxygen; b) a source of bicarbonate ions; c) a source of thio functional groups; d) a source of metal ion catalyst; e) at least one organic polyphosphate; and f) an organic buffer 2) containing the stable reference solution in a sealed environment, said environment having a head space which contains at least about 93% gas selected from the group nitrogen, noble gasses and mixtures thereof and the remainder comprising CO 2 ; 3) subsequently removing the stable reference solution from the sealed environment; and, 4) equilibrating the stable reference solution with a gas mixture containing N 2 , CO 2 and O 2 in amounts which provide physiological ranges of pH, pCO 2 and pO 2 in the solution.
Claim 57
Independent Claim
187 words
A method for providing a reference standard for blood gas and CO-Oximetry instrumentation comprising the steps of: 1) providing a stable reference solution which comprises an aqueous mixture containing: a) a hemoglobin solution comprising fractions of: i) at least about 95% reduced hemoglobin, ii) less than about 3% methemoglobin, iii) less than about 2% carboxyhemoglobin, iv) less than 2% oxyhemoglobin, and v) less than about 0.3% by volume oxygen; b) a source of bicarbonate ions; c) a source of thio functional groups; d) a source of metal ion catalyst; e) at least one organic polyphosphate; and f) an organic buffer 2) containing the stable reference solution in a sealed environment, said environment having a head space which contains at least about 93% gas selected from the group nitrogen, noble gasses and mixtures thereof and the remainder comprising CO 2 ; 3) subsequently removing the stable reference solution from the sealed environment; and, 4) equilibrating the stable reference solution with a gas mixture containing N 2 , CO 2 and O 2 in amounts which provide physiological ranges of pH, pCO 2 and pO 2 in the solution.
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1994-09-02 | 1995-03-04 | 1995-09-03 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1998-09-02 | 1999-03-04 | 1999-09-03 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2002-09-02 | 2003-03-04 | 2003-09-03 | $7700.00 | Window Closed / Lapsed |