Patent US6417084B1 successfully refreshed from Google Patents.
US4470970A
Expired / Lapsed
US
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Purified antineoplaston fractions and methods of treating neoplastic disease
Assignee: Individual
•
Filing: 1981-12-15
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Granted: 1984-09-11
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Expires: 2001-12-15
Abstract
Abstract Highly purified fractions from human urine exhibiting antineoplastic activity and processes for their preparation are described. The fractions comprise biologically active, small sized, low molecular weight peptides which exert cytostatic and cytotoxic activity toward neoplastic cell cultures and human neoplastic diseases. The fractions have been termed antineoplaston fractions. An antineoplastic active peptide common to each of the various antineoplaston fractions has been isolated and identified as 3-[N-phenylacetylaminopiperidine]-2, 6-dion. A synthetic mechanism for the preparation of 3-[N-phenylacetylaminopiperdine]-2, 6-dion is also disclosed, involving a combination reaction between L-glutamine and phenylacetyl chloride. Also disclosed are the hydrolysis degradation products of 3-[N-phenylacetylaminopiperidine]-2, 6-dion which also exhibit antineoplastic activity when administered according to the general teachings presented in this disclosure.
Inventors
- 👤 Stanislaw R. Burzynski
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-01 11:01
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/435; C07K14/46; C07K14/47; A; A61; A61K; A61K31/00; A61K31/185; A61K31/19; A61K31/195; A61K31/33; A61K31/395; A61K31/435; A61K31/44; A61K31/445; A61P; A61P31/00; A61P31/04; A61P35/00; C07K4/00; C07K4/12; A61K38/00; Y; Y10; Y10S; Y10S530/00; Y10S530/827; Y10S530/834
Claims Analysis
Total Claims: 57
Claim 1
Independent Claim
74 words
A process for extracting from urine a peptide fraction containing the compound 3-[N-phenylacetylaminopiperidine]-2, 6-dion comprising the steps of: providing a volume of urine; separating from the urine particulate matter and matter having a molecular weight greater than from about 5000; acidifying the urine; separating from the acidified urine any precipitated matter; introducing the acidified urine to a chromatography column; and recovering the cytostatic active peptide fraction, said peptide fraction containing the compound 3-[N-phenylacetylaminopiperidine]-2, 6-dion.
Claim 2
Dependent Claim
74 words
A process for extracting from urine a peptide fraction containing the compound 3-[N-phenylacetylaminopiperidine]-2, 6-dion comprising the steps of: providing a volume of urine; separating from the urine particulate matter and matter having a molecular weight greater than from about 5000; acidifying the urine; separating from the acidified urine any precipitated matter; introducing the acidified urine to a chromatography column; and recovering the cytostatic active peptide fraction, said peptide fraction containing the compound 3-[N-phenylacetylaminopiperidine]-2, 6-dion.
Claim 3
Dependent Claim
20 words
The process of claim 1 wherein the urine is acidified to a pH ranging from about 2 to about 3.
Claim 4
Dependent Claim
14 words
The process of claim 1 wherein the urine is acidified to about pH 2.5.
Claim 5
Dependent Claim
18 words
The process of claim 1 wherein the acidified urine is introduced to a high performance liquid chromatography column.
Claim 6
Dependent Claim
19 words
The process of claim 4 wherein the high performance liquid chromatography is conducted on C-18 bonded phase silica gel.
Claim 7
Dependent Claim
17 words
The process of claim 1 which further comprises: purifying from the peptide fraction the compound 3-[N-phenylacetylaminopiperidine]-2, 6-dion.
Claim 8
Dependent Claim
18 words
The process of claim 6 wherein the purification is accomplished by a second high performance liquid chromatography operation.
Claim 9
Dependent Claim
32 words
The process of claim 7 wherein the second high performance liquid chromatography operation is conducted on sulfonated polystyrene according to the Glenco Scientific, Inc., system for amino acids, or an equivalent system.
Claim 10
Dependent Claim
11 words
A product made in accordance with the process of claim 1.
Claim 11
Dependent Claim
88 words
A product made in accordance with the process of claim 1 having a characteristic chromatograph shown in FIG. 1 of the drawings wherein the chromatograph represents the refractive index pattern of peaks developed by high performance liquid chromatography conducted on a C-18 bonded phase type silica gel after sequential washings with a first wash of about 1000 ml of water; a second wash with about 1000 ml acetic acid solution; a third wash with about 1000 ml of water; and a final wash with 600 ml of methanol.
Claim 12
Dependent Claim
107 words
A process for extracting from urine a peptide fraction containing the compound 3-[N-phenylacetylaminopiperidine]-2, 6-dion comprising the steps of: providing a volume of urine; separating from the urine particulate matter and matter having a molecular weight greater than about 5000; acidifying the urine; separating from the acidified urine any precipitated matter; introducing the acidified urine to a first chromatography column containing a polymeric resin adsorbent; eluting the column to recover an eluate; adjusting the pH of the eluate to between about 2 and 8; introducing the adjusted eluate to a second chromatography column; and recovering the cytostatic active peptide fraction, said peptide fraction containing the compound 3-[N-phenylacetylaminopiperidine]-2, 6-dion.
Claim 13
Dependent Claim
107 words
A process for extracting from urine a peptide fraction containing the compound 3-[N-phenylacetylaminopiperidine]-2, 6-dion comprising the steps of: providing a volume of urine; separating from the urine particulate matter and matter having a molecular weight greater than about 5000; acidifying the urine; separating from the acidified urine any precipitated matter; introducing the acidified urine to a first chromatography column containing a polymeric resin adsorbent; eluting the column to recover an eluate; adjusting the pH of the eluate to between about 2 and 8; introducing the adjusted eluate to a second chromatography column; and recovering the cytostatic active peptide fraction, said peptide fraction containing the compound 3-[N-phenylacetylaminopiperidine]-2, 6-dion.
Claim 14
Dependent Claim
17 words
The process of claim 11 wherein the column is eluted with water, alcohol, or mixtures of both.
Claim 15
Dependent Claim
16 words
The process of claim 11 wherein the second chromatography column contains C-18 bonded phase silica gel.
Claim 16
Dependent Claim
20 words
The process of claim 11 wherein the urine is acidified to a pH ranging from about 1 to about 2.
Claim 17
Dependent Claim
14 words
The process of claim 11 wherein the urine is acidified to about pH 1.5.
Claim 18
Dependent Claim
13 words
The process of claim 11 wherein the polymeric resin adsorbent is Amberlite XAD-8.
Claim 19
Dependent Claim
17 words
The process of claim 11 wherein the pH of the eluate is adjusted to about pH 2.5.
Claim 20
Dependent Claim
17 words
The process of claim 11 which further comprises: purifying from the peptide fraction the compound 3-[N-phenylacetylaminopiperidine]-2, 6-dion.
Claim 21
Dependent Claim
17 words
The process of claim 18 wherein the purification is accomplished by a high performance liquid chromatography operation.
Claim 22
Dependent Claim
27 words
The process of claim 19 wherein the high performance liquid chromatography operation is conducted on sulfonated polystyrene according to the Glenco Scientific, Inc., system for amino acids.
Claim 23
Dependent Claim
11 words
The product made in accordance with the process of claim 11.
Claim 24
Dependent Claim
89 words
The product made in accordance with process of claim 11 having a characteristic chromatograph shown in FIG. 2 of the drawings wherein the chromatograph represents the refractive index pattern of peaks developed by high performance liquid chromatography conducted on a C-18 bonded phase type silica gel after sequential washings with a first wash of about 1000 ml of water; a second wash with about 1000 ml acetic acid solution, pH 2.5; a third wash with about 1000 ml of water; and a final wash with 600 ml of methanol.
Claim 25
Dependent Claim
119 words
A process for extracting from urine a peptide fraction containing the compound 3-[N-phenylacetylaminopiperidine]-2, 6-dion comprising the steps of: providing a volume of urine; separating from the urine particulate matter and matter having a molecular weight greater than about 5000; acidifying the urine; separating from the acidified urine any precipitated matter; introducing the acidified urine to a first chromatography column containing a resin adsorbent; eluting the column with an alkaline wash; collecting the alkaline wash eluate; adjusting the pH of the alkaline wash eluate from about pH 2 to about 8; oxidizing the acidified eluate; introducing the oxidized acidified eluate to a second chromatography column; and recovering the cytostatic active peptide fraction, said peptide fraction containing the compound 3-[N-phenylacetylaminopiperidine]-2, 6-dion.
Claim 26
Dependent Claim
119 words
A process for extracting from urine a peptide fraction containing the compound 3-[N-phenylacetylaminopiperidine]-2, 6-dion comprising the steps of: providing a volume of urine; separating from the urine particulate matter and matter having a molecular weight greater than about 5000; acidifying the urine; separating from the acidified urine any precipitated matter; introducing the acidified urine to a first chromatography column containing a resin adsorbent; eluting the column with an alkaline wash; collecting the alkaline wash eluate; adjusting the pH of the alkaline wash eluate from about pH 2 to about 8; oxidizing the acidified eluate; introducing the oxidized acidified eluate to a second chromatography column; and recovering the cytostatic active peptide fraction, said peptide fraction containing the compound 3-[N-phenylacetylaminopiperidine]-2, 6-dion.
Claim 27
Dependent Claim
20 words
The process of claim 23 wherein the acidified eluate is oxidized before introducing the eluate to the second chromatography column.
Claim 28
Dependent Claim
16 words
The process of claim 23 wherein the second chromatography column contains C-18 bonded phase silica gel.
Claim 29
Dependent Claim
20 words
The process of claim 23 wherein the urine is acidified to a pH ranging from about 1 to about 2.
Claim 30
Dependent Claim
14 words
The process of claim 23 wherein the urine is acidified to about pH 1.5.
Claim 31
Dependent Claim
13 words
The process of claim 23 wherein the polymeric resin adsorbent is Amberlite XAD-8.
Claim 32
Dependent Claim
23 words
The process of claim 23 wherein the pH of the alkaline wash eluate is adjusted to a pH ranging from 2 to 3.
Claim 33
Dependent Claim
15 words
The process of claim 23 wherein the resulting acidified solution is oxidized with potassium permanganate.
Claim 34
Dependent Claim
17 words
The process of claim 23 which further comprises: purifying from the peptide fraction the compound 3-[N-phenylacetylaminopiperidine]-2, 6-dione.
Claim 35
Dependent Claim
17 words
The process of claim 31 wherein the purification is accomplished by a high performance liquid chromatography operation.
Claim 36
Dependent Claim
27 words
The process of claim 32 wherein the high performance liquid chromatography operation is conducted on sulfonated polystyrene according to the Glenco Scientific, Inc., system for amino acids.
Claim 37
Dependent Claim
11 words
A product made in accordance with the process of claim 23.
Claim 38
Dependent Claim
89 words
A product made in accordance with the process of claim 23 having a characteristic chromatograph shown in FIG. 3 of the drawings wherein the chromatograph represents the refractive index pattern of peaks developed by high performance liquid chromatography conducted on a C-18 bonded phase type silica gel after sequential washings with a first wash of about 1000 ml of water; a second wash with about 1000 ml acetic acid solution, pH 2.5; a third wash with about 1000 ml of water; and a final wash with 600 ml methanol.
Claim 39
Dependent Claim
72 words
A process for extracting from urine a peptide fraction containing the compound 3-[N-phenylacetylaminopiperidine]-2, 6-dion comprising the steps of: providing a volume of urine; subjecting the urine to oxidation; adjusting the pH of the urine to between about 2 and about 8; removing from the oxidized urine any precipitated matter; introducing the oxidized urine to a chromatography column; and recovering the cytostatic active peptide fraction, said peptide fraction containing the compound 3-[N-phenylacetylaminopiperidine]-2, 6-dion.
Claim 40
Dependent Claim
72 words
A process for extracting from urine a peptide fraction containing the compound 3-[N-phenylacetylaminopiperidine]-2, 6-dion comprising the steps of: providing a volume of urine; subjecting the urine to oxidation; adjusting the pH of the urine to between about 2 and about 8; removing from the oxidized urine any precipitated matter; introducing the oxidized urine to a chromatography column; and recovering the cytostatic active peptide fraction, said peptide fraction containing the compound 3-[N-phenylacetylaminopiperidine]-2, 6-dion.
Claim 41
Dependent Claim
18 words
The process of claim 36 wherein the urine is acidified to a pH ranging from 2 to 3.
Claim 42
Dependent Claim
16 words
The process of claim 36 wherein the chromatography is conducted on C-18 bonded phase silica gel.
Claim 43
Dependent Claim
17 words
The process of claim 36 which further comprises: purifying from the peptide fraction the compound 3-[N-phenylacetylaminopiperidine]-2, 6-dion.
Claim 44
Dependent Claim
17 words
The process of claim 39 wherein the purification is accomplished by a high performance liquid chromatography operation.
Claim 45
Dependent Claim
27 words
The process of claim 39 wherein the high performance liquid chromatography operation is conducted on sulfonated polystyrene according to the Glenco Scientific, Inc., system for amino acids.
Claim 46
Dependent Claim
11 words
A product made in accordance with the process of claim 36.
Claim 47
Dependent Claim
90 words
A product made in accordance with the process of claim 36 having a characteristic chromatograph shown in FIG. 4 of the drawings wherein the chromatograph represents the refractive index pattern of peaks developed by high performance liquid chromatography conducted on a C-18 bonded phase type silica gel after sequential washings with a first wash of about 1000 ml of water; a second wash with about 1000 ml of acetic acid solution, pH 2.5; a third wash with about 1000 ml of water; and a final wash with 600 ml methanol.
Claim 48
Dependent Claim
88 words
A process for extracting from urine a peptide fraction containing the compound 3-[N-phenylacetylaminopiperidine]-2, 6-dione comprising the steps of: providing a volume of urine; separating from the urine particulate matter and matter having a molecular weight greater than about 5000; acidifying the urine; separating from the acidified urine any precipitated matter; introducing the acidified urine to a chromatography column; eluting the column with a lower alkyl alcohol having from 1 to 8 carbon atoms; and recovering the cytostatic active peptide fraction, said peptide fraction containing the compound 3-[N-phenylacetylaminopiperidine]-2, 6-dion.
Claim 49
Dependent Claim
88 words
A process for extracting from urine a peptide fraction containing the compound 3-[N-phenylacetylaminopiperidine]-2, 6-dione comprising the steps of: providing a volume of urine; separating from the urine particulate matter and matter having a molecular weight greater than about 5000; acidifying the urine; separating from the acidified urine any precipitated matter; introducing the acidified urine to a chromatography column; eluting the column with a lower alkyl alcohol having from 1 to 8 carbon atoms; and recovering the cytostatic active peptide fraction, said peptide fraction containing the compound 3-[N-phenylacetylaminopiperidine]-2, 6-dion.
Claim 50
Dependent Claim
20 words
The process of claim 44 wherein the urine is acidified to a pH ranging from about 2 to about 3.
Claim 51
Dependent Claim
14 words
The process of claim 44 wherein the urine is acidified to about pH 2.5.
Claim 52
Dependent Claim
17 words
The process of claim 44 wherein the acidified urine is introduced to a high performance chromatography column.
Claim 53
Dependent Claim
18 words
The process of claim 44 wherein the high performance chromatography is conducted on C-18 bonded phase silica gel.
Claim 54
Dependent Claim
17 words
The process of claim 44 which further comprises: purifying from the peptide fraction the compound 3-[N-phenylacetylaminopiperidine]-2, 6-dion.
Claim 55
Dependent Claim
16 words
The process of claim 49 wherein the purification is accomplished by a high performance chromatography operation.
Claim 56
Dependent Claim
11 words
A product made in accordance with the process of claim 44.
Claim 57
Dependent Claim
90 words
A product made in accordance with the process of claim 44 having a characteristic chromatograph shown in FIG. 5 of the drawings wherein the chromatograph represents the refractive index pattern of peaks developed by high performance liquid chromatography conducted on a C-18 bonded phase type silica gel after sequential washings with a first wash of about 1000 ml of water; a second wash with about 1000 ml acetic acid solution, pH 2.5; a third wash with about 1000 ml of water; and a final wash with 600 ml of methanol.
References Cited (Backward Citations)
No citation records indexed.
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1987-09-11 | 1988-03-12 | 1988-09-11 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-09-11 | 1992-03-12 | 1992-09-11 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-09-11 | 1996-03-12 | 1996-09-11 | $7700.00 | Window Closed / Lapsed |