US4988799A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Lignosulfonate based pharmacologic agent with anti-coagulant and anti-thrombotic activity
Assignee: Ligno Tech USA
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Filing: 1987-08-11
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Granted: 1991-01-29
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Expires: 2007-08-11
Abstract
Abstract A lignosulfonate useful pharmacologically as an anti-thrombotic that inhibits deep venous thrombophlebitis without effecting blood coagulation, and which causes no apparent increased bleeding or side effects. The lignosulfonate is isolated from softwood spent sulfite liquor, and is administered in low dosages of from about 0.05 to about 1.0 mg/milliter of blood. A method of making and administering the lignosulfonate is also disclosed.
Inventors
- 👤 Russell H. Samson
- 👤 John W. Hollis, Jr.
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 00:34
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/70; A61K31/715; A61K36/00; A61P; A61P7/00; A61P7/02; C; C08; C08H; C08H6/00
Claims Analysis
Total Claims: 18
Claim 1
Independent Claim
184 words
A method of making a pharmacologic agent having anti-thrombotic activity, comprising the steps of: liquid-liquid extracting an aqueous mixture of a substantially sulfite-free spent sulfite liquor having a pH of 2 to 6 with an amine dissolved in a water immiscible alcohol to form an amine-lignosulfonate-alcohol liquid phase and an aqueous phase, wherein the amount of amine added to the sulfite liquor is 60-70% molarly equivalent to the original spent sulfite liquor sulfonic sulfur content; separating the amine-lignosulfonate-alcohol liquid phase from the aqueous phase; liquid-liquid extracting the amine-lignosulfonate-alcohol liquid phase with an alkali to form a M-lignosulfonate aqueous phase having a pH of 8 to 14, where M is selected from ammonium, sodium, potassium, lithium, calcium and magnesium, and a substantially lignosulfonate-free amine-alcohol liquid phase; separating the M-lignosulfonate aqueous phase from the amine-alcohol liquid phase; reducing the alkaline pH of the M-lignosulfonate aqueous phase to a substantially neutral pH while simultaneously forming insoluble impurities subsequent to the separation of the M-lignosulfonate and amine-alcohol liquid phases by treating the M-lignosulfonate aqueous phase with a cation exchange resin; and separating the insoluble impurities from the M-lignosulfonate.
Claim 2
Independent Claim
184 words
A method of making a pharmacologic agent having anti-thrombotic activity, comprising the steps of: liquid-liquid extracting an aqueous mixture of a substantially sulfite-free spent sulfite liquor having a pH of 2 to 6 with an amine dissolved in a water immiscible alcohol to form an amine-lignosulfonate-alcohol liquid phase and an aqueous phase, wherein the amount of amine added to the sulfite liquor is 60-70% molarly equivalent to the original spent sulfite liquor sulfonic sulfur content; separating the amine-lignosulfonate-alcohol liquid phase from the aqueous phase; liquid-liquid extracting the amine-lignosulfonate-alcohol liquid phase with an alkali to form a M-lignosulfonate aqueous phase having a pH of 8 to 14, where M is selected from ammonium, sodium, potassium, lithium, calcium and magnesium, and a substantially lignosulfonate-free amine-alcohol liquid phase; separating the M-lignosulfonate aqueous phase from the amine-alcohol liquid phase; reducing the alkaline pH of the M-lignosulfonate aqueous phase to a substantially neutral pH while simultaneously forming insoluble impurities subsequent to the separation of the M-lignosulfonate and amine-alcohol liquid phases by treating the M-lignosulfonate aqueous phase with a cation exchange resin; and separating the insoluble impurities from the M-lignosulfonate.
Claim 3
Dependent Claim
22 words
The method of claim 1 wherein said alkali is selected from the group consisting of lithium, ammonium, potassium, calcium and sodium hydroxide.
Claim 4
Dependent Claim
23 words
The method of claim 1 wherein said alkali is selected from the group consisting of hydroxides and carbonates of ammonia, calcium and magnesium.
Claim 5
Dependent Claim
11 words
The method of claim 1 wherein said amine is diemthylhexadecyl amine.
Claim 6
Dependent Claim
26 words
The method of claim 1 further including the step of purifying the M-lignosulfonate aqueous phase to remove substantially all traces of the amine and the alcohol.
Claim 7
Dependent Claim
15 words
The method of claim 5 wherein said purifying step comprises stripping the M-lignosulfonate with steam.
Claim 8
Dependent Claim
29 words
The method of claim 6 further comprising the step of evaporating the M-lignosulfonate in a flash concentrator with intermittent water addition subsequent to the steam stripping of the M-lignosulfonate.
Claim 9
Dependent Claim
12 words
The method of claim 1 wherein said lignosulfonate is obtained from softwoods.
Claim 10
Dependent Claim
10 words
The method of claim 1 wherein said alcohol is isooctanol.
Claim 11
Dependent Claim
15 words
The method of claim 1 wherein said cation exchange resin is a sulfonated polystyrene resin.
Claim 12
Dependent Claim
36 words
A pharmaceutical composition comprising a lignosulfonate prepared by the process of claim 1 in an amount effective to inhibit thrombus formation in blood without effecting blood coagulation; and a pharmaceutically acceptable inert carrier for said lignosulfonate.
Claim 13
Dependent Claim
12 words
The pharmaceutical composition of claim 11 wherein said inert carrier is water.
Claim 14
Dependent Claim
13 words
The pharmaceutical composition of claim 11 wherein said inert carrier is blood plasma.
Claim 15
Independent Claim
219 words
A method of administering a pharmaceutical composition, comprising the steps of: preparing a softwood lignosulfonate by liquid-liquid extracting an aqueous mixture of a substantially sulfite-free spent sulfite liquor having a pH of 2 to 6 with an amine dissolved in a water immiscible alcohol to form an amine-lignosulfonate-alcohol liquid phase and an aqueous phase, wherein the amount of amine added to the sulfite liquor is 60-70% molarly equivalent to the original spent sulfite liquor sulfonic sulfur content; separating the amine-lignosulfonate-alcohol liquid phase from the aqueous phase; liquid-liquid extracting the amine-lignosulfonate-alcohol liquid phase with an alkali to form a M-lignosulfonate aqueous phase having a pH of 8 to 14, where M is selected from ammonium, sodium, potassium, lithium, calcium and magnesium, and a substantially lignosulfonate-free amine-alcohol liquid phase; separating the M-lignosulfonate aqueous phase from the amine-alcohol liquid phase; reducing the alkaline pH of the M-lignosulfonate aqueous phase to a substantially neutral pH while simultaneously forming insoluble impurities subsequent to the separation of the M-lignosulfonate and amine-alcohol liquid phases by treating the M-lignosulfonate aqueous phase with a cation exchange resin; separating the insoluble impurities from the M-lignosulfonate; mixing said lignosulfonate with a pharmaceutically acceptable inert carrier; and administering said mixture to a patient at a low dosage in an amount effective to inhibit thrombus formation in blood without affecting blood coagulation.
Claim 16
Independent Claim
219 words
A method of administering a pharmaceutical composition, comprising the steps of: preparing a softwood lignosulfonate by liquid-liquid extracting an aqueous mixture of a substantially sulfite-free spent sulfite liquor having a pH of 2 to 6 with an amine dissolved in a water immiscible alcohol to form an amine-lignosulfonate-alcohol liquid phase and an aqueous phase, wherein the amount of amine added to the sulfite liquor is 60-70% molarly equivalent to the original spent sulfite liquor sulfonic sulfur content; separating the amine-lignosulfonate-alcohol liquid phase from the aqueous phase; liquid-liquid extracting the amine-lignosulfonate-alcohol liquid phase with an alkali to form a M-lignosulfonate aqueous phase having a pH of 8 to 14, where M is selected from ammonium, sodium, potassium, lithium, calcium and magnesium, and a substantially lignosulfonate-free amine-alcohol liquid phase; separating the M-lignosulfonate aqueous phase from the amine-alcohol liquid phase; reducing the alkaline pH of the M-lignosulfonate aqueous phase to a substantially neutral pH while simultaneously forming insoluble impurities subsequent to the separation of the M-lignosulfonate and amine-alcohol liquid phases by treating the M-lignosulfonate aqueous phase with a cation exchange resin; separating the insoluble impurities from the M-lignosulfonate; mixing said lignosulfonate with a pharmaceutically acceptable inert carrier; and administering said mixture to a patient at a low dosage in an amount effective to inhibit thrombus formation in blood without affecting blood coagulation.
Claim 17
Dependent Claim
21 words
The method of claim 14 wherein said low dosage comprises an amount of about 0.05 to about 1.0 mg/milliter of blood.
Claim 18
Dependent Claim
17 words
The method of claim 14 wherein the M-lignosulfonate aqueous phase has a pH of 9.5 to 11.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1994-01-28 | 1994-07-30 | 1995-01-29 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1998-01-28 | 1998-07-30 | 1999-01-29 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2002-01-28 | 2002-07-30 | 2003-01-29 | $7700.00 | Window Closed / Lapsed |