Patent US4372874A successfully refreshed from Google Patents.
US4372874A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Stabilization of hydrolysis prone labile organic reagents in liquid media
Assignee: Medical Analysis Systems Inc
•
Filing: 1980-11-13
•
Granted: 1983-02-08
•
Expires: 2000-11-13
Abstract
Abstract A labile, organic reagent, which is unstable in aqueous media and stable in a nonaqueous media, is stabilized by dissolving the organic reagent in a water-miscible, organic solvent which is liquid at room temperature and which is nondegradatively reactive with the organic reagent to form a solution of the organic reagent in the organic solvent. At least 1% of an inert, high-surface area particulate desiccant is added to the solution for entrapping water with the desiccant so that the residual water content of the solution is below about 0.5%. The desiccant can be removed from the solution before sealing it. More than one organic reagent can be added to the solvent, and a solubilizing agent for the organic reagent can be used.
Inventors
- 👤 Ivan E. Modrovich
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-24 11:09
CPC Classifications
G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; C; C07; C07D; C07D307/00; C07D307/02; C07D307/34; C07D307/56; C07D307/62; C07J; C07J9/00; C12; C12Q; C12Q1/00; C12Q1/008; Y; Y10; Y10T; Y10T436/00; Y10T436/10; Y10T436/107497; Y10T436/25; Y10T436/2525
Claims Analysis
Total Claims: 51
Claim 1
Independent Claim
187 words
A method for stabilizing a labile organic reagent which is unstable in aqueous media and stable in nonaqueous media, comprising in combination the steps of: (a) dissolving at least one organic reagent selected from the group consisting of adenosine monophosphate, adenosine diphsophate, adenosine triphosphate, phosphoadenylic acid sulfate, adenosylmethionine, uridine diphosphate, cytidine diphosphate, coenzyme A, tetrahydrofolic acid, biotin, thiamine pyrophosphate, pryidoxal phosphate, nicotinamide mononucleotide, cell haemin, B 12 coenzyme, NADP, NADPH, purine nucleotides, pyrimidine nucleotides, cholesterol, magnesium thymolphthalein monophosphate, dithioerythritol, dithiothreitol, N-acetyl cysteine, glutathione, mercaptoethanol, o-cresolphthalein complexone, N-acetyl cystine, gamma glutamyl-p-nitroanilide, bilirubin, paranitrophenyl phosphate, phenolphthalein monophosphate, glycerol phosphate, p-nitroanilide, p-nitrophenol, ascorbic acid, tetraphenylboron, phosphoenol pyruvate, B-NAD and hydrated NADH 2 , in a water miscible organic solvent which is liquid at room temperature and which is nondegradatively reactive with such organic reagent to form a solution of such organic reagent in the organic solvent; and (b) providing in contact with the solution at least one percent by weight of an inert, high surface area, particulate desiccant for entrapping water to provide a residual water content in the solution below about 0.5% by weight; and (c) sealing the solution.
Claim 2
Independent Claim
187 words
A method for stabilizing a labile organic reagent which is unstable in aqueous media and stable in nonaqueous media, comprising in combination the steps of: (a) dissolving at least one organic reagent selected from the group consisting of adenosine monophosphate, adenosine diphsophate, adenosine triphosphate, phosphoadenylic acid sulfate, adenosylmethionine, uridine diphosphate, cytidine diphosphate, coenzyme A, tetrahydrofolic acid, biotin, thiamine pyrophosphate, pryidoxal phosphate, nicotinamide mononucleotide, cell haemin, B 12 coenzyme, NADP, NADPH, purine nucleotides, pyrimidine nucleotides, cholesterol, magnesium thymolphthalein monophosphate, dithioerythritol, dithiothreitol, N-acetyl cysteine, glutathione, mercaptoethanol, o-cresolphthalein complexone, N-acetyl cystine, gamma glutamyl-p-nitroanilide, bilirubin, paranitrophenyl phosphate, phenolphthalein monophosphate, glycerol phosphate, p-nitroanilide, p-nitrophenol, ascorbic acid, tetraphenylboron, phosphoenol pyruvate, B-NAD and hydrated NADH 2 , in a water miscible organic solvent which is liquid at room temperature and which is nondegradatively reactive with such organic reagent to form a solution of such organic reagent in the organic solvent; and (b) providing in contact with the solution at least one percent by weight of an inert, high surface area, particulate desiccant for entrapping water to provide a residual water content in the solution below about 0.5% by weight; and (c) sealing the solution.
Claim 3
Dependent Claim
26 words
The method as recited in claim 1 further comprising the step of removing substantially all of the desiccant from the solution prior to sealing the solution.
Claim 4
Dependent Claim
26 words
The method of claim 1 in which the solvent comprises a polyol containing from 2 to 4 hydroxyl groups and from 2 to 10 carbon atoms.
Claim 5
Dependent Claim
12 words
The method of claim 3 in which the solvent is a 1,2-propanediol.
Claim 6
Dependent Claim
20 words
The method of claim 1 in which the desiccant is a molecular sieve present in an amount from 5-20% v/v.
Claim 7
Dependent Claim
17 words
The method of claim 5 in which the desiccant has a particle size from about 2-16 mesh.
Claim 8
Dependent Claim
63 words
The method of claim 1 in which the organic reagent is selected from the group consisting of: gamma-glutamyl-p-nitroanilide paranitrophenyl phosphate phenophthalein monophosphate glycerol phosphate p-nitroanilide p-nitrophenol ascorbic acid tetraphenylboron bilirubin phosphoenol pyruvate cholesterol magnesium thymolphthalein monophosphate dithioerythritol dithiothreitol N-acetyl cysteine glutathione mercaptoethanol o-cresolphthalein complexone N-acetyl cystine adenosine triphosphate β-nicotinamide adenine dinucleotide NADPH NADP hydrated NADH 2 adenosine monophosphate adenosine diphosphate and combinations thereof.
Claim 9
Dependent Claim
30 words
The method of claim 1 including the step of adding to the solvent a solubilizing agent for the organic reagent, wherein the solubilizing agent is nondegradatively reactive with the reagent.
Claim 10
Dependent Claim
26 words
The method of claim 8 in which the solubilizing agent is selected from the group consisting of boric acid, imidazole, salycilate, ascorbic acid, and combinations thereof.
Claim 11
Dependent Claim
29 words
The method of claim 1 in which the dissolving step comprises adding gamma glutamyl-p-nitroanilide to a solvent selected from the group consisting of dimethyl sulfoxide, acetone, and combinations thereof.
Claim 12
Dependent Claim
20 words
The method of claim 10 including the step of adding boric acid to the solvent for solubilizing the gamma glutamyl-p-nitroanilide.
Claim 13
Dependent Claim
23 words
The method of claim 1 in which the step of dissolving comprises dissolving cholesterol in a solvent comprising tetrahydrofuran, dimethyl sulfoxide, and isopropanol.
Claim 14
Dependent Claim
23 words
The method of claim 1 in which the step of dissolving comprises dissolving magnesium thymolphthalein monophosphate in a solvent comprising phenol and methanol.
Claim 15
Dependent Claim
46 words
The method of claim 1 in which the organic reagent is selected from the group consisting of dithiothreitol, dithioerythritol, N-acetyl cysteine, glutathione, mercaptoethanol, and combinations thereof, and the solvent is a polyol containing from 2 to 4 hydroxyl groups and from 4 to 10 carbon atoms.
Claim 16
Dependent Claim
21 words
The method of claim 1 in which the step of dissolving comprises dissolving o-cresolphthalein complexone in a solvent comprising dimethyl sulfoxide.
Claim 17
Dependent Claim
22 words
The method of claim 1 in which the step of dissolving comprises dissolving o-cresolphthalein complexone in a solvent comprising phenol and methanol.
Claim 18
Dependent Claim
33 words
The method of claim 1 in which the step of dissolving comprises dissolving a salt of phosphoenol pyruvate in a solvent selected from the group consisting of dimethyl sulfoxide, acetone, and combinations thereof.
Claim 19
Dependent Claim
18 words
The method of claim 17 wherein the salt of phosphoenol pyruvate is the monocyclohexylammonium salt of phosphoenol pyruvate.
Claim 20
Dependent Claim
33 words
The method of claim 1 wherein the step of dissolving comprises dissolving a salt of β-nicotinamide adenine dinucleotide in a solvent selected from the group consisting of ethanol, ethylene glycol, and combinations thereof.
Claim 21
Dependent Claim
34 words
The method of claim 1 in which the step of dissolving comprises dissolving a lithium salt (C 21 H 26 N 7 O 14 Li.2H 2 O) of β-nicotinamide adenine dinucleotide phosphate in solvent.
Claim 22
Dependent Claim
18 words
The method of claim 1 in which the step of dissolving comprises dissolving ascorbic acid in dimethyl sulfoxide.
Claim 23
Dependent Claim
29 words
The method of claim 10 in which the dissolving step further comprises selecting dimethyl sulfoxide as the solvent and dissolving paranitrophenyl phosphate and gamma glutamyl-p-nitroanilide in the dimethyl sulfoxide.
Claim 24
Dependent Claim
32 words
The method of claim 11 in which the dissolving step further comprises selecting dimethyl sulfoxide as the solvent and dissolving paranitrophenyl phosphate and gamma glutamyl-p-nitroanilide in the dimethyl sulfoxide and boric acid.
Claim 25
Dependent Claim
16 words
The method as recited in claim 1 wherein the desiccant is not removed from the solution.
Claim 26
Dependent Claim
26 words
The method of claim 24 in which the solvent comprises a polyol containing from 2 to 4 hydroxyl groups and from 2 to 10 carbon atoms.
Claim 27
Dependent Claim
12 words
The method of claim 25 in which the solvent is a 1,2-propanediol.
Claim 28
Dependent Claim
22 words
The method of claim 25 in which the desiccant is a molecular sieve present in an amount from 5 to 20% v/v.
Claim 29
Dependent Claim
19 words
The method of claim 27 in which the desiccant has a particle size from about 2 to 16 mesh.
Claim 30
Dependent Claim
62 words
The method of claim 24 in which the organic reagent is selected from the group consisting of: gamma-glutamyl-p-nitroanilide paranitrophenyl phosphate phenophthalein monophosphate glycerol phosphate p-nitroanilide p-nitrophenol ascorbic acid tetraphenylboron phosphoenol pyruvate cholesterol magnesium thymolphthalein monophosphate dithioerythritol dithiothreitol N-acetyl cysteine glutathione mercaptoethanol o-cresolphthalein complexone N-acetyl cystine adenosine triphosphate β-nicotinamide adenine dinucleotide NADPH NADP hydrated NADH 2 adenosine monophosphate adenosine diphosphate and combinations thereof.
Claim 31
Dependent Claim
30 words
The method of claim 24 including the step of adding to the solvent a solubilizing agent for the organic reagent, wherein the solubilizing agent is nondegradatively reactive with the reagent.
Claim 32
Dependent Claim
26 words
The method of claim 30 in which the solubilizing agent is selected from the group consisting of boric acid, imidazole, salycilate, ascorbic acid, and combinations thereof.
Claim 33
Dependent Claim
27 words
The method of claim 24 in which the step of adding gamma glutamyl-p-nitroanilide, a solvent selected from the group consisting of dimethyl sulfoxide, acetone, and combinations thereof.
Claim 34
Dependent Claim
19 words
The method of claim 32 including the step of adding boric acid to the solvent for solubilizing the reagent.
Claim 35
Dependent Claim
23 words
The method of claim 24 in which the step of dissolving comprises dissolving cholesterol in a solvent comprising tetrahydrofuran, dimethyl sulfoxide, and isopropanol.
Claim 36
Dependent Claim
23 words
The method of claim 24 in which the step of dissolving comprises dissolving magnesium thymolphthalein monophosphate in a solvent comprising phenol and methanol.
Claim 37
Dependent Claim
46 words
The method of claim 24 in which the organic reagent is selected from the group consisting of dithiothreitol, dithioerythritol, N-acetyl cysteine, glutathione, mercaptoethanol and combinations thereof, and the solvent is a polyol containing from 2 to 4 hydroxyl groups and from 4 to 10 carbon atoms.
Claim 38
Dependent Claim
21 words
The method of claim 24 in which the step of dissolving comprises dissolving o-cresolphthalein complexone in a solvent comprising dimethyl sulfoxide.
Claim 39
Dependent Claim
22 words
The method of claim 24 in which the step of dissolving comprises dissolving o-cresolphthalein complexone in a solvent comprising phenol and methanol.
Claim 40
Dependent Claim
33 words
The method of claim 24 in which the step of dissolving comprises dissolving a salt of phosphoenol pyruvate in a solvent selected from the group consisting of dimethyl sulfoxide, acetone, and combinations thereof.
Claim 41
Dependent Claim
18 words
The method of claim 39 wherein the salt of phosphoenol pyruvate is the monocyclohexylammonium salt of phosphoenol pyruvate.
Claim 42
Dependent Claim
33 words
The method of claim 24 wherein the step of dissolving comprises dissolving a salt of β-nicotinamide adenine dinucleotide in a solvent selected from the group consisting of ethanol, ethylene glycol, and combinations thereof.
Claim 43
Dependent Claim
34 words
The method of claim 24 in which the step of dissolving comprises dissolving a lithium salt (C 21 H 26 N 7 O 14 Li.2H 2 O) of β-nicotinamide adenine dinucleotide phosphate in solvent.
Claim 44
Dependent Claim
18 words
The method of claim 24 in which the step of dissolving comprises dissolving ascorbic acid in dimethyl sulfoxide.
Claim 45
Dependent Claim
29 words
The method of claim 32 in which the dissolving step further comprises selecting dimethyl sulfoxide as the solvent and dissolving paranitrophenyl phosphate and gamma glutamyl-p-nitroanilide in the dimethyl sulfoxide.
Claim 46
Dependent Claim
32 words
The method of claim 33 in which the dissolving step further comprises selecting dimethyl sulfoxide as the solvent and dissolving paranitrophenyl phosphate and gamma glutamyl-p-nitroanilide in the dimethyl sulfoxide and boric acid.
Claim 47
Dependent Claim
16 words
A product prepared by the method of claim 24 comprising the solution sealed with the desiccant.
Claim 48
Independent Claim
118 words
A method for stabilizing a labile organic reagent which is unstable in aqueous media and stable in a nonaqueous media comprising in combination the steps of: (a) dissolving at least one such organic reagent in a water-miscible, organic solvent which is liquid at room temperature and which is nondegradatively reactive with such organic reagent to form a solution of such organic reagent in the organic solvent; and (b) providing in contact with the solution at least 1% by weight of an inert, high-surface area particulate desiccant for entrapping water; (c) maintaining the desiccant in the solution for a time sufficient to reduce the residual water content of the solution to below about 0.5%; and (d) sealing the solution.
Claim 49
Independent Claim
118 words
A method for stabilizing a labile organic reagent which is unstable in aqueous media and stable in a nonaqueous media comprising in combination the steps of: (a) dissolving at least one such organic reagent in a water-miscible, organic solvent which is liquid at room temperature and which is nondegradatively reactive with such organic reagent to form a solution of such organic reagent in the organic solvent; and (b) providing in contact with the solution at least 1% by weight of an inert, high-surface area particulate desiccant for entrapping water; (c) maintaining the desiccant in the solution for a time sufficient to reduce the residual water content of the solution to below about 0.5%; and (d) sealing the solution.
Claim 50
Independent Claim
134 words
A method for stabilizing a labile organic reagent which is unstable in aqueous media and stable in a nonaqueous media comprising the steps of: (a) dissolving at least one solubilizing agent for the organic reagent in a water-miscible, organic solvent which is liquid at room temperature and which is nondegradatively reactive with the organic reagent, wherein the solubilizing agent is nondegradatively reactive with the organic reagent; (b) adding the organic reagent to the organic solvent and stirring the solvent; (c) filtering the solution to remove any debris or undissolved reagent or solubilizing agent; (d) adding at least 1% by weight of an inert, high-surface area particulate desiccant, to the solution for entrapping water with the desiccant so that the residual water content of the solution is below about 0.5%; and (e) sealing the solution.
Claim 51
Independent Claim
134 words
A method for stabilizing a labile organic reagent which is unstable in aqueous media and stable in a nonaqueous media comprising the steps of: (a) dissolving at least one solubilizing agent for the organic reagent in a water-miscible, organic solvent which is liquid at room temperature and which is nondegradatively reactive with the organic reagent, wherein the solubilizing agent is nondegradatively reactive with the organic reagent; (b) adding the organic reagent to the organic solvent and stirring the solvent; (c) filtering the solution to remove any debris or undissolved reagent or solubilizing agent; (d) adding at least 1% by weight of an inert, high-surface area particulate desiccant, to the solution for entrapping water with the desiccant so that the residual water content of the solution is below about 0.5%; and (e) sealing the solution.
References Cited (Backward Citations)
DE1365651U
Cited
US2356890A
Cited
US3235089A
Cited
FR1267604A
Cited
GB1027430A
Cited
BE663418A
Cited
US3519570A
Cited
US3539450A
Cited
US3479154A
Cited
US3557002A
Cited
US3546131A
Cited
US3642444A
Cited
US3764478A
Cited
US3748272A
Cited
US3761420A
Cited
US3819487A
Cited
US3704806A
Cited
US3776900A
Cited
US3926735A
Cited
US3876375A
Cited
US3876375B1
Cited
US3853473A
Cited
US3894844A
Cited
NL7603588A
Cited
DE2615958A1
Cited
US3986834A
Cited
US4017420A
Cited
US4153511A
Cited
US4218536A
Cited
US4239649A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1986-02-07 | 1986-08-09 | 1987-02-08 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1990-02-07 | 1990-08-09 | 1991-02-08 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1994-02-07 | 1994-08-09 | 1995-02-08 | $7700.00 | Window Closed / Lapsed |