US4313875A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Purification of penicillin derivative
Assignee: Tanabe Pharma Corp
•
Filing: 1980-08-27
•
Granted: 1982-02-02
•
Expires: 2000-08-27
Abstract
Abstract Crude 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenyla cetamido]penicillanic acid can be purified by the steps of: (A) contacting an aqueous solution of 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenyla cetamido]-penicillanic acid with a nonpolar, macroporous styrenedivinylbenzyl copolymer adsorption resin to adsorb 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenyla cetamido]penicillanic acid on the resin, (B) eluting the adsorbed 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenyla cetamido]penicillanic acid with water or a mixture of water and a water-miscible organic solvent, and then (C) isolating pure 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenyla cetamido]penicillanic acid from the eluates.
Inventors
- 👤 Etsumi Nakamura
- 👤 Takashi Suzuki
- 👤 Tadasu Yanagida
- 👤 Minehiko Yamamura
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 16:23
CPC Classifications
C; C07; C07D; C07D499/00
Claims Analysis
Total Claims: 19
Claim 1
Independent Claim
64 words
A method for purification of crude 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetamido]penicillanic acid which comprises the steps of: (A) contacting an aqueous solution of 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetamido]penicillanic acid with a nonpolar, macroporous styrenedivinylbenzyl copolymer adsorption resin to absorb 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetamido]penicillanic acid on the resin, (B) eluting the absorbed 6-[D-2-(D-2-amino-3-N-methylcarbamoylpropionamido)-2-p-hydroxyphenylacetamido]penicillanic acid with water or a mixture of water and a water-miscible organic solvent, and then (C) isolating pure 6-[D-2-(D-2-amino-3-N-methylcarbamoylpropionamido)-2-p-hydroxyphenylacetamido]penicillanic acid from the eluates.
Claim 2
Independent Claim
64 words
A method for purification of crude 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetamido]penicillanic acid which comprises the steps of: (A) contacting an aqueous solution of 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetamido]penicillanic acid with a nonpolar, macroporous styrenedivinylbenzyl copolymer adsorption resin to absorb 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetamido]penicillanic acid on the resin, (B) eluting the absorbed 6-[D-2-(D-2-amino-3-N-methylcarbamoylpropionamido)-2-p-hydroxyphenylacetamido]penicillanic acid with water or a mixture of water and a water-miscible organic solvent, and then (C) isolating pure 6-[D-2-(D-2-amino-3-N-methylcarbamoylpropionamido)-2-p-hydroxyphenylacetamido]penicillanic acid from the eluates.
Claim 3
Dependent Claim
41 words
The method according to claim 1, wherein the resin is a styrene-divinylbenzene copolymer having a pore volume of 0.6 to 1.1 ml/g, a specific surface area of 200 to 800 m 2 /g and a particle size of 45 to 840μ.
Claim 4
Dependent Claim
30 words
The method according to claim 2, wherein the mixture of water and a water-miscible organic solvent is a mixture of water and an alkanol having one to 3 carbon atoms.
Claim 5
Dependent Claim
32 words
The method according to claim 2, wherein the mixture of water and a water-miscible organic solvent is 2 to 8 v/v % aqueous methanol or 2 to 8 v/v % aqueous ethanol.
Claim 6
Dependent Claim
48 words
The method according to claim 2, wherein the concentration of 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetamido]penicillanic acid present in the aqueous solution thereof is 0.5 to 25 w/v %, and the volume of the resin to be used is 3 to 100 ml per gram of 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetamido]penicillanic acid present in the aqueous solution.
Claim 7
Dependent Claim
83 words
The method according to claim 1, wherein the adsorption and elution steps are carried out by passing said aqueous solution of 6-[D-2-(D-2-amino-3-N-methylcarbamoylpropionamido)-2-p-hydroxyphenylacetamido]penicillanic acid through a column packed with said nonpolar, macroporous styrene-divinylbenzene copolymer adsorption resin at a space velocity of 0.1 to 5 to adsorb 6 -[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetamido]penicillanic acid on the resin, and then passing water or a mixture of water and a water-miscible organic solvent through the column at a space velocity of 0.3 to 15 to elute the adsorbed 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetamido]penicillanic acid therefrom.
Claim 8
Dependent Claim
27 words
The method according to claim 6, wherein the elution step is carried out by passing water through the column at a space velocity of 0.5 to 5.
Claim 9
Dependent Claim
35 words
The method according to claim 6, wherein the elution step is carried out by passing the mixture of water and a water-miscible organic solvent through the column at a space velocity of 1 to 3.
Claim 10
Independent Claim
94 words
A method for purification of an aqueous solution containing 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetamido]penicillanic acid in admixture with a penicilloic acid, the condensate of said penicillanic and penicilloic acids, colored substances and D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetic acid (or amoxicillin), which comprises the steps of: (A) passing said aqueous solution through a column packed with a nonpolar, macroporous styrene-divinylbenzene copolymer adsorption resin to adsorb 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetamido]penicillanic acid on the resin, (B) passing water or a mixture of water and a water-miscible organic solvent through the column to elute the adsorbed 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetamido]penicillanic acid therefrom, and then, (C) isolating pure 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetamido]penicillanic acid from the eluates.
Claim 11
Independent Claim
94 words
A method for purification of an aqueous solution containing 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetamido]penicillanic acid in admixture with a penicilloic acid, the condensate of said penicillanic and penicilloic acids, colored substances and D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetic acid (or amoxicillin), which comprises the steps of: (A) passing said aqueous solution through a column packed with a nonpolar, macroporous styrene-divinylbenzene copolymer adsorption resin to adsorb 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetamido]penicillanic acid on the resin, (B) passing water or a mixture of water and a water-miscible organic solvent through the column to elute the adsorbed 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetamido]penicillanic acid therefrom, and then, (C) isolating pure 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetamido]penicillanic acid from the eluates.
Claim 12
Dependent Claim
133 words
The method according to claim 9, which comprises the steps of: (A) passing said aqueous solution through the column at a space velocity of 0.1 to 5 to adsorb 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetamido]penicillanic acid, said penicilloic acid, the condensate of said penicillanic and penicilloic acids, colored substances and D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetic acid (or amoxicillin) on the resin, (B) (a) passing water through the column at a space velocity of 0.3 to 15 to elute the adsorbed 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetamido]penicillanic acid therefrom, or (b) (i) washing the column with water to remove D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetic acid (or amoxicillin) and said penicilloic acid therefrom, and (ii) passing a mixture of water and a water-miscible organic solvent through the column at a space velocity of 0.3 to 5 to elute the adsorbed 6-[D-2-(D-2-amino-3-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetamido]penicillanic acid therefrom, and then, (C) isolating pure 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetamido]penicillanic acid from the eluates.
Claim 13
Dependent Claim
41 words
The method according to claim 9, wherein the resin is a styrene-divinylbenzene copolymer having a pore volume of 0.6 to 1.1 ml/g, a specific surface area of 200 to 800 m 2 /g, and a particle size of 45 to 840μ.
Claim 14
Dependent Claim
48 words
The method according to claim 10, wherein the concentration of 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetamido]penicillanic acid present in the aqueous solution thereof is 0.5 to 25 w/v %, and the volume of the resin to be used is 3 to 100 ml per gram of 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetamido]penicillanic acid present in the aqueous solution.
Claim 15
Dependent Claim
30 words
The method according to claim 12, wherein the mixture of water and a water-miscible organic solvent is a mixture of water and an alkanol having one to 3 carbon atoms.
Claim 16
Dependent Claim
32 words
The method according to claim 12, wherein the mixture of water and a water-miscible organic solvent is 2 to 8 v/v % aqueous methanol or 2 to 8 v/v % aqueous ethanol.
Claim 17
Dependent Claim
29 words
The method according to claim 12, wherein the elution of 6-[D-2-(D-2-amino-3-N-methylcarbamoyl-propionamido)-2-p-hydroxyphenylacetamido]penicillanic acid is carried out by passing water through the column at a space velocity of 0.5 to 5.
Claim 18
Dependent Claim
33 words
The method according to claim 14, wherein the elution of 6-[D-2-(D-2-amino-3-N-methylcarbamoylamino-propionamido)-2-p-hydroxyphenylacetamido]penicillanic acid is carried out by passing the aqueous methanol or ethanol through the column at a space velocity of 1 to 3.
Claim 19
Independent Claim
26 words
The method according to any one of claims 1-16 wherein said isolating is carried out by condensation, freeze concentration, concentration by reverse osmosis, or freeze drying.
References Cited (Backward Citations)
US4053609A
Cited
US4206218A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1985-02-01 | 1985-08-03 | 1986-02-02 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1989-02-01 | 1989-08-03 | 1990-02-02 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1993-02-01 | 1993-08-03 | 1994-02-02 | $7700.00 | Window Closed / Lapsed |