US5681567A
Expired / Lapsed
US
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Method of preparing polyalkylene oxide carboxylic acids
Assignee: Viskase Holdings Inc
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Filing: 1996-08-13
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Granted: 1997-10-28
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Expires: 2016-08-13
Abstract
Abstract The present invention is directed to methods of preparing high purity polyalkylene oxide carboxylic acids. The methods include reacting a polyalkylene oxide such as polyethylene glycol with a t-butyl haloacetate in the presence of a base followed by treatment with an acid such as trifluoroacetic acid. The resultant polymer carboxylic acids are of sufficient purity so that expensive and time containing purification steps required for pharmaceutical grade polymers are avoided.
Inventors
- 👤 Anthony J. Martinez
- 👤 Richard B. Greenwald
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-03 03:04
CPC Classifications
C; C08; C08G; C08G65/00; C08G65/02; C08G65/32; C08G65/338; A; A61; A61K; A61K47/00; A61K47/50; A61K47/51; A61K47/56; A61K47/59; A61K47/60; C08G65/329; C08G65/331; C08G65/332; C08G65/3322; C08G65/333; C08G65/33396; C08G65/337
Claims Analysis
Total Claims: 27
Claim 1
Independent Claim
93 words
A method of preparing a biologically active conjugate, comprising: i) reacting a polyalkylene oxide with a tertiary alkyl haloacetate in the presence of a base to form a tertiary alkyl ester of polyalkylene oxide; ii) reacting said tertiary alkyl ester with an acid to form a polyalkylene oxide containing a terminal carboxylic acid; and iii) reacting said polyalkylene oxide containing said terminal carboxylic acid with a biologically active nucleophile under conditions sufficient to form a biologically active conjugate whereby said polyalkylene oxide is linked to said biologically active nucleophile by an ester linkage.
Claim 2
Independent Claim
93 words
A method of preparing a biologically active conjugate, comprising: i) reacting a polyalkylene oxide with a tertiary alkyl haloacetate in the presence of a base to form a tertiary alkyl ester of polyalkylene oxide; ii) reacting said tertiary alkyl ester with an acid to form a polyalkylene oxide containing a terminal carboxylic acid; and iii) reacting said polyalkylene oxide containing said terminal carboxylic acid with a biologically active nucleophile under conditions sufficient to form a biologically active conjugate whereby said polyalkylene oxide is linked to said biologically active nucleophile by an ester linkage.
Claim 3
Dependent Claim
12 words
The method of claim 1, wherein said polyalkylene oxide is polyethylene glycol.
Claim 4
Dependent Claim
13 words
The method of claim 1, wherein said polyalkylene oxide is omega methoxypolyethylene glycol.
Claim 5
Dependent Claim
41 words
The method of claim 1, wherein said tertiary alkyl haloacetate comprises the formula: ##STR3## wherein X is chlorine, bromine or iodine; R 1-3 are independently selected from the group consisting of C 1-8 alkyls, or C 1-8 branched alkyls and aryls.
Claim 6
Dependent Claim
14 words
The method of claim 4, wherein R 1-3 are independently selected C 1-3 alkyls.
Claim 7
Dependent Claim
10 words
The method of claim 4, wherein R 1-3 are methyl.
Claim 8
Dependent Claim
15 words
The method of claim 4, wherein said tertiary alkyl haloacetate is a tertiary butyl haloacetate.
Claim 9
Dependent Claim
12 words
The method of claim 7, wherein said t-butyl haloacetate is t-butyl bromoacetate.
Claim 10
Dependent Claim
12 words
The method of claim 7, wherein said t-butyl haloacetate is t-butyl chloroacetate.
Claim 11
Dependent Claim
11 words
The method of claim 1, wherein said base is potassium t-butoxide.
Claim 12
Dependent Claim
22 words
The method of claim 1, wherein said base is selected from the group consisting of butyl lithium, sodium amide and sodium hydride.
Claim 13
Dependent Claim
22 words
The method of claim 1, wherein the molar ratio of said tertiary alkyl haloacetate to said polyalkylene oxide is greater than 1:1.
Claim 14
Dependent Claim
11 words
The method of claim 1, wherein said acid is trifluoroacetic acid.
Claim 15
Dependent Claim
20 words
The method of claim 1, wherein said acid is selected from the group consisting of sulfuric, phosphoric and hydrochloric acids.
Claim 16
Dependent Claim
24 words
The method of claim 1, wherein said reacting step ii) is carried out at a temperature of from about 0° to about 50° C.
Claim 17
Dependent Claim
24 words
The method of claim 15, wherein said reacting step ii) is carried out at a temperature of from about 20° to about 30° C.
Claim 18
Dependent Claim
18 words
The method of claim 1, wherein said reacting step ii) is carried out in the presence of water.
Claim 19
Dependent Claim
22 words
The method of claim 1, wherein said polyalkylene oxide has a number average molecular weight of from about 200 to about 100,000.
Claim 20
Dependent Claim
22 words
The method of claim 18, wherein said polyalkylene oxide has a number average molecular weight of from about 2,000 to about 80,000.
Claim 21
Dependent Claim
22 words
The method of claim 19, wherein said polyalkylene oxide has a number average molecular weight of from about 4,000 to about 50,000.
Claim 22
Dependent Claim
18 words
The method of claim 1, wherein the purity of said polyalkylene oxide carboxylic acid is greater than 92%.
Claim 23
Dependent Claim
18 words
The method of claim 21, wherein the purity of said polyalkylene oxide carboxylic acid is greater than 97%.
Claim 24
Dependent Claim
18 words
The method of claim 22, wherein the purity of said polyalkylene oxide carboxylic acid is greater than 99%.
Claim 25
Dependent Claim
12 words
The method of claim 1, wherein said biologically active nucleophile is taxol.
Claim 26
Dependent Claim
12 words
The method of claim 1, wherein said biologically active nucleophile is camptothecin.
Claim 27
Dependent Claim
12 words
The method of claim 1, wherein said biologically active nucleophile is podophyllotoxin.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2000-10-27 | 2001-04-28 | 2001-10-28 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2004-10-27 | 2005-04-28 | 2005-10-28 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2008-10-27 | 2009-04-28 | 2009-10-28 | $7700.00 | Window Closed / Lapsed |