US4863902A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Treatment of cancer
Assignee: Wakunaga Pharmaceutical Co Ltd
•
Filing: 1986-11-28
•
Granted: 1989-09-05
•
Expires: 2006-11-28
Abstract
Abstract Antitumor effect of antitumor agents or treatments is favorably controlled by a growth factor. The growth factor enhances antitumor actions of antitumor agents or treatments including those against which tumor or cancer has acquired resistant, or reduces side effects due to the antitumor agents or treatments. The most typical growth factors include human epidermal growth factor. A lot of tumors or cancers including human ones has been tested and a lot of growth factors has been tested, and the favorable control has been determined.
Inventors
- 👤 Harunobu Amagase
- 👤 Masato Arakawa
- 👤 Ken Hashimoto
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 17:45
CPC Classifications
A; A61; A61K; A61K45/00; A61K45/06; A61K33/00; A61K33/24; A61K33/243; A61K38/00; A61K38/16; A61K38/17; A61K38/18; A61K38/1808; A61K38/1825; A61K38/1841; A61K38/22; A61K38/28; A61K38/30; A61K33/16
Claims Analysis
Total Claims: 64
Claim 1
Independent Claim
156 words
An antitumor composition, comprising (a) a compound having antitumor action which is at least one compound selected from the group consisting of alkylating agents, antimetabolites, antibiotics and platinum complexes, and (b) a growth factor which is at least one compound selected from the group consisting of compounds of the epidermal growth factor family and compounds of the platelet-derived growth factor family; wherein said alkylating agents are selected from the group consisting of chloromethyne analogues, nitrogen mustard analogues, ethyleneimino analogues, alkylsulfonic acid analogues, nitrosourea analogues, and epoxide analogues; wherein said antimetabolites are selected from the group consisting of folic acid antagonist analogues, purine antagonist analogues, pyridine antagonist analogues, Tegafur, and uracil formulated into Tegafur; wherein said antibiotics are selected from the group consisting of actinomycin analogues, azaserine, DON, sarkomycin, carzinophilin, mitomycin analogues, chromomycin A 3 analogues, bleomycin, peplomycin, daunorubicin, adriamycin, and aclarubicin; and wherein said platinum complexes are selected from the group consisting of cisplatin, carboplatin, ipuloplatin.
Claim 2
Dependent Claim
156 words
An antitumor composition, comprising (a) a compound having antitumor action which is at least one compound selected from the group consisting of alkylating agents, antimetabolites, antibiotics and platinum complexes, and (b) a growth factor which is at least one compound selected from the group consisting of compounds of the epidermal growth factor family and compounds of the platelet-derived growth factor family; wherein said alkylating agents are selected from the group consisting of chloromethyne analogues, nitrogen mustard analogues, ethyleneimino analogues, alkylsulfonic acid analogues, nitrosourea analogues, and epoxide analogues; wherein said antimetabolites are selected from the group consisting of folic acid antagonist analogues, purine antagonist analogues, pyridine antagonist analogues, Tegafur, and uracil formulated into Tegafur; wherein said antibiotics are selected from the group consisting of actinomycin analogues, azaserine, DON, sarkomycin, carzinophilin, mitomycin analogues, chromomycin A 3 analogues, bleomycin, peplomycin, daunorubicin, adriamycin, and aclarubicin; and wherein said platinum complexes are selected from the group consisting of cisplatin, carboplatin, ipuloplatin.
Claim 3
Dependent Claim
54 words
An antitumore composition according to claim 1, wherein the compound having antitumor action, component (a), is an alkylating agent, and the growth factor or the growth factor equivalent, component (b), is a compound belonging to the epidermal growth factor family, a peptide corresponding to a part of its constituent or a derivative of these.
Claim 4
Dependent Claim
149 words
An antitumor composition according to claim 1, wherein the alkylating agent is cyclophosphamide or a derivative thereof or a salt of these, and the compound belonging to the epidermal cell growth factor family, the peptide growth corresponding to a part of its constituent and the derivative of these is at least one compound selected from the group consisting of human epidermal growth factor (hereinafter written as hEGF), the derivative of human epidermal growth factor in which methionine which is the 21st amino acid from the N-terminal of the human epidermal growth factor is converted to leucine (hereinafter written as [Leu 21 ]-hEGF), the derivative of human epidermal growth factor in which two amino acids from the C-terminal (leucine and alginine) of the human epidermal growth factor are lacking (hereinafter written as hEGF-II), transforming growth factor α (hereinafter written as TGF.sub.α), and transforming growth factor β (hereinafter written as TGF.sub.β).
Claim 5
Dependent Claim
48 words
An antitumor agent according to claim 1, wherein the alkylating agent is cyclophosphamide or its derivative or a salt of these, and the compound belonging to the epidermal growth factor family, or the peptide corresponding to a part of its constituent or the derivative of these is hEGF.
Claim 6
Dependent Claim
49 words
An antitumor agent according to claim 1, wherein the alkylating agent is cyclophosphamide or its derivative or a salt of these, and the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent or the derivative of these is [Leu 21 ]-hEGF.
Claim 7
Dependent Claim
47 words
An antitumor agent according to claim 1, wherein the alkylating agent is cyclophosphamide or its derivative or a salt of these, and the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent or the derivative of these is hEGF-II.
Claim 8
Dependent Claim
47 words
An antitumor agent according to claim 1, wherein the alkylating agent is cyclophosphamide or its derivative or a salt of these, and the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent or the derivative of these is TGF.sub.α.
Claim 9
Dependent Claim
52 words
An antitumor agent according to claim 1, wherein the alkylating agent is cyclophosphamide or its derivative or a salt of these, and the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent or the derivative of these is a mixture of hEGF and TGF.sub.β.
Claim 10
Dependent Claim
14 words
An antitumor agent according to claim 3, wherein cyclophosphamide or its derivative is cyclophosphamide.
Claim 11
Dependent Claim
53 words
An antitumor agent according to claim 1, wherein the compound having antitumor action, component (a), is an antimetabolite, and the growth factor or the growth factor equivalent, component (b), is a compound belonging to the epidermal growth factor family, a peptide corresponding to a part of its constituent or a derivative of these.
Claim 12
Dependent Claim
79 words
An antitumor agent according to claim 1, wherein the antimetabolite is at least one compound or a mixture selected from 5-fluorouracil, or its derivative or salts of these, Tegafur or its derivative or salts of these, or a mixture of Tegafur or its derivative or salts of these with uracil, and the compound belonging to the epidermal growth factor family, the growth factor equivalent is at least one compound selected from hEGF, [Leu 21 ]-hEGF, hEGF-II, TGF.sub.α and TGF.sub.β.
Claim 13
Dependent Claim
47 words
An antitumor agent according to claim 1, wherein the antimetabolite is 5-fluorouracil or its derivative or a salt of these, and the compound belonging to the epidermal growth factor family, the growth factor equivalent to a part of its constituent or the derivative of these is hEGF.
Claim 14
Dependent Claim
38 words
An antitumor agent according to claim 1, wherein the antimetabolite is 5-fluorouracil or its derivative or a salt of these, and the compound belonging to the epidermal growth factor family, the growth factor equivalent is [Leu 21 ]-hEGF.
Claim 15
Dependent Claim
46 words
An antitumor agent according to claim 1, wherein the antimetabolite is 5-fluorouracil or its derivative or a salt of these, and the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent or the derivative of these is hEGF-II.
Claim 16
Dependent Claim
46 words
An antitumor agent according to claim 1, wherein the antimetabolite is 5-fluorouracil or its derivative or a salt of these, and the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent or the derivative of these is TGF.sub.α.
Claim 17
Dependent Claim
51 words
An antitumor agent according to claim 1, wherein the antimetabolite is 5-fluorouracil or its derivative or a salt of these, and the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent or the derivative of these is a mixture of hEGF and TGF.sub.β.
Claim 18
Dependent Claim
14 words
An antitumor agent according to claim 11, wherein 5-fluorouracil or its derivative is 5-fluorouracil.
Claim 19
Dependent Claim
46 words
An antitumor agent according to claim 1, wherein the antimetabolite is Tegafur or its derivative or a salt of these, and the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent or the derivative of these is hEGF.
Claim 20
Dependent Claim
48 words
An antitumor agent according to claim 1, wherein the antimetabolite is Tegafur or its derivative or a salt of these, and the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent or the derivative of these is [Leu 21 ]-hEGF.
Claim 21
Dependent Claim
46 words
An antitumor agent according to claim 1, wherein the antimetabolite is Tegafur or its derivative or a salt of these, and the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent or the derivative of these is hEGF-II.
Claim 22
Dependent Claim
46 words
An antitumor agent according to claim 1, wherein the antimetabolite is Tegafur or its derivative or a salt of these, and the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent or the derivative of these is TGF.sub.α.
Claim 23
Dependent Claim
51 words
An antitumor agent according to claim 1, wherein the antimetabolite is Tegafur or its derivative or a salt of these, and the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent or the derivative of these is a mixture of hEGF and TFG.
Claim 24
Dependent Claim
51 words
An antitumor agent according to claim 1, wherein the antimetabolite is a mixture of Tegafur or its derivative or a salt of these and uracil, and the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent or the derivative of these is hEGF.
Claim 25
Dependent Claim
53 words
An antitumor agent according to claim 1, wherein the antimetabolite is a mixture of Tegafur or its derivative of a salt of these and uracil, and the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent or the derivative of these is [Leu 21 ]-hEGF.
Claim 26
Dependent Claim
51 words
An antitumor agent according to claim 1, wherein the antimetabolite is a mixture of Tegafur or its derivative of a salt of these and uracil, and the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent or the derivative of these is hEGF-II.
Claim 27
Dependent Claim
51 words
An antitumor agent according to claim 1, wherein the antimetabolite is a mixture of Tegafur or its derivative or a salt of these and uracil, and the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent or the derivative of these is TGF.sub.α.
Claim 28
Dependent Claim
56 words
An antitumor agent according to claim 1, wherein the antimetabolite is a mixture of Tegafur or its derivative or a salt of these and uracil, and the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent or the derivative of these is a mixture of hEGF and TGF.sub.β.
Claim 29
Dependent Claim
14 words
An antitumor agent according to claim 19, wherein Tegafur or its derivative is Tegafur.
Claim 30
Dependent Claim
54 words
An antitumor agent according to claim 1, wherein the compound having antitumor action, component (a), is an antimetabolite, and the growth factor or the growth factor equivalent, component (b), is a compound belonging to the platelet derived growth factor family, a peptide corresponding to a part of its constituent or a derivative of these.
Claim 31
Dependent Claim
82 words
An antitumor agent according to claim 1, wherein the antimetabolite is at least one compound or a mixture selected from 5-fluorouracil, or its derivative or salts of these, Tegafur or its derivative or salts of these, or a mixture of Tegafur or its derivative or salts of these with uracil, and the compound belonging to the platelet-derived growth factor family, the peptide corresponding to a part of its constituent or the derivative of these is fibroblast growth factor (hereinafter written a FGF).
Claim 32
Dependent Claim
46 words
An antitumor agent according to claim 1, wherein the antimetabolite is 5-fluorouracil, or its derivative or a salt of these, and the compound belonging to the platelet-derived growth factor family, the peptide corresponding to a part of its constituent or the derivative of these is FGF.
Claim 33
Dependent Claim
14 words
An antitumor agent according to claim 30, wherein 5-fluorouracil or its derivatives is 5-fluorouracil.
Claim 34
Dependent Claim
46 words
An antitumor agent according to claim 1, wherein the antimetabolite is Tegafur, or its derivative or a salt of these, and the compound belonging to the platelet-derived growth factor family, the peptide corresponding to a part of its constituent or the derivative of these is FGF.
Claim 35
Dependent Claim
51 words
An antitumor agent according to claim 1, wherein the antimetabolites is a mixture of Tegafur, or its derivative or a salt of these and uracil, and the compound belonging to the platelet-derived growth factor family, the peptide corresponding to a part of its constituent or the derivative of these is FGF.
Claim 36
Dependent Claim
14 words
An antitumor agent according to claim 33, wherein Tegafur or its derivatives is Tegafur.
Claim 37
Dependent Claim
40 words
An antitumor agent according to claim 1, wherein the compound having antitumor action, component (a), is an antitumor antibiotic, and the growth factor or the growth factor equivalent, component (b), is a compound belonging to the epidermal growth factor family.
Claim 38
Dependent Claim
68 words
An antitumor agent according to claim 1, wherein the antibiotic is at least one compound selected from mitomycin, derivatives thereof or salts thereof, or adriamycin, or derivative thereof or salts thereof, and the compound belonging to the epidermal cell growth family, the peptide corresponding to a part of its constituent and the derivative of these is at least one compound selected from hEGF, hEGF-II and [Leu 21 ]-hEGF.
Claim 39
Dependent Claim
46 words
An antitumor agent according to claim 1, wherein the antibiotic is mitomycin, a derivative thereof or a salt of these, and the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent, or the derivative of these is hEGF.
Claim 40
Dependent Claim
46 words
An antitumor agent according to claim 1, wherein the antibiotic is mitomycin, a derivative thereof or a salt of these, and the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent, or the derivative of these is hEGF-II.
Claim 41
Dependent Claim
48 words
An antitumor agent according to claim 1, wherein the antibiotic is mitomycin, a derivative thereof or a salt of these, and the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent, or the derivative of these is [Leu 21 ]-hEGF.
Claim 42
Dependent Claim
15 words
An antitumor agent according to claim 37, wherein mitomycin or its derivative is mitomycin C.
Claim 43
Dependent Claim
46 words
An antitumor agent according to claim 1, wherein the antibiotic is adriamycin, a derivative thereof or a salt of these, and the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent, or the derivative of these is hEGF.
Claim 44
Dependent Claim
46 words
An antitumor agent according to claim 1, wherein the antibiotic is adriamycin, a derivative thereof or a salt of these, and the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent, or the derivative of these is hEGF-II.
Claim 45
Dependent Claim
48 words
An antitumor agent according to claim 1, wherein the antibiotic is adriamycin, a derivative thereof or a salt of these, and the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent, or the derivative of these is [Leu 21 ]-hEGF.
Claim 46
Dependent Claim
14 words
An antitumor agent according to claim 42, wherein adriamycin or its derivative is adriamycin.
Claim 47
Dependent Claim
14 words
An antitumor agent according to claim 39, wherein adriamycin, or its derivative is adriamycin.
Claim 48
Dependent Claim
41 words
An antitumor agent according to claim 1, wherein the compound having antitumor action, component (a), is a platinum complex, and the growth factor or the growth factor equivalent, component (b), is a compound belonging to the epidermal cell growth factor family.
Claim 49
Dependent Claim
69 words
An antitumor agent according to claim 1, wherein the compound having antitumor action is one member selected from the group consisting of cisplatin, derivatives thereof and salts thereof, adriamycin, derivatives thereof and salts thereof, and the compound belonging to the epidermal growth family, the peptide corresponding to part of its constituent and the derivative of these is at least one compound selected from hEGF, hEGF-II and [Leu 21 ]-hEGF.
Claim 50
Dependent Claim
47 words
An antitumor agent according to claim 1, wherein the platinum complex is cisplatin, a derivative thereof or a salt of these, and the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent, or the derivative of these is hEGF.
Claim 51
Dependent Claim
47 words
An antitumor agent according to claim 1, wherein the platinum complex is cisplatin, a derivative thereof or a salt of these, and the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent, or the derivative of these is hEGF-II.
Claim 52
Dependent Claim
49 words
An antitumor agent according to claim 1, wherein the platinum complex is cisplatin, a derivative thereof or a salt of these, and the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent, or the derivative of these is [Leu 21 ]-hEGF.
Claim 53
Dependent Claim
14 words
An antitumor agent according to claim 48, wherein cisplatin or its derivative is cisplatin.
Claim 54
Independent Claim
192 words
A method of controlling antitumor action in chemotherapy, radiation therapy or thermotherapy in which antitumor treatment is practiced, which method comprises administering to a patient under said treatment, during or after the application to the patient of an antitumor chemical which is at least one compound selected from the group consisting of alkylating agents, antimetabolites, antibiotics and platinum complexes, irradiation or heat, an antitumor controlling composition, comprising a growth factor which is at least one compound selected from the group consisting of compounds of the epidermal growth factor family and compounds of the platelet-derived growth factor family; wherein said alkylating agents are selected from the group consisting of chloromethyne analogues, nitrogen mustard analogues, ethyleneimino analogues, alkylsulfonic acid analogues, nitrosourea analogues, and epoxide analogues; wherein said antimetabolites are selected from the group consisting of folic acid antagonist analogues, purine antagonist analogues, pyridine antagonist analogues, Tegafur, and uracil formulated into Tegafur; wherein said antibiotics are selected from the group consisting of actinomycin analogues, azaserine, DON, sarkomycin, carzinophilin, mitomycin analogues, chromomycin A 3 analogues, bleomycin, peplomycin, daunorubicin, adriamycin, and aclarubicin; and wherein said platinum complexes are selected from the group consisting of cisplatin, carboplatin, ipuloplatin.
Claim 55
Independent Claim
192 words
A method of controlling antitumor action in chemotherapy, radiation therapy or thermotherapy in which antitumor treatment is practiced, which method comprises administering to a patient under said treatment, during or after the application to the patient of an antitumor chemical which is at least one compound selected from the group consisting of alkylating agents, antimetabolites, antibiotics and platinum complexes, irradiation or heat, an antitumor controlling composition, comprising a growth factor which is at least one compound selected from the group consisting of compounds of the epidermal growth factor family and compounds of the platelet-derived growth factor family; wherein said alkylating agents are selected from the group consisting of chloromethyne analogues, nitrogen mustard analogues, ethyleneimino analogues, alkylsulfonic acid analogues, nitrosourea analogues, and epoxide analogues; wherein said antimetabolites are selected from the group consisting of folic acid antagonist analogues, purine antagonist analogues, pyridine antagonist analogues, Tegafur, and uracil formulated into Tegafur; wherein said antibiotics are selected from the group consisting of actinomycin analogues, azaserine, DON, sarkomycin, carzinophilin, mitomycin analogues, chromomycin A 3 analogues, bleomycin, peplomycin, daunorubicin, adriamycin, and aclarubicin; and wherein said platinum complexes are selected from the group consisting of cisplatin, carboplatin, ipuloplatin.
Claim 56
Dependent Claim
52 words
A method of controlling antitumor action according to claim 53, wherein the growth factor, the peptide corresponding to a part of its constituent and the derivative of these is a compound belonging to the epidermal growth factor family, a peptide corresponding to a part of its constituent or a derivative of these.
Claim 57
Dependent Claim
134 words
A method of controlling antitumor action according to claim 54, wherein the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent and the derivative of these is at least one compound selected from the group consisting of human epidermal growth factor (hereinafter written as hEGF), the derivative of human epidermal growth factor in which methionine which is the 21st amino acid from the N-terminal of human epidermal growth factor is converted to leucine (hereinafter written as [Leu 21 ]-hEGF), the derivative of human epidermal growth factor in which two amino acids from the C-terminal (leucine and alginine) of the human epidermal growth factor are lacking (hereinafter written as hEGF-II), transforming growth factor α (hereinafter written as TGSF.sub.α), and transforming growth factor β (hereinafter written as TGF.sub.β).
Claim 58
Dependent Claim
36 words
A method of controlling antitumor action according to claim 55, wherein the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent or the derivative of these is hEGF.
Claim 59
Dependent Claim
36 words
A method of controlling antitumor action according to claim 55, wherein the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent or the derivative of these is -hEGF.
Claim 60
Dependent Claim
36 words
A method of controlling antitumor action according to claim 55, wherein the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent or the derivative of these is hEGF-II.
Claim 61
Dependent Claim
36 words
A method of controlling antitumor action according to claim 53, wherein the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent or the derivative of these is TGF.sub.α.
Claim 62
Dependent Claim
41 words
A method of controlling antitumor action according to claim 55, wherein the compound belonging to the epidermal growth factor family, the peptide corresponding to a part of its constituent or the derivative of these is a mixture of hEGF and TGF.sub.β.
Claim 63
Dependent Claim
43 words
A method for controlling antitumor action according to claim 53, wherein the growth factor, or the growth factor equivalent is a compound belonging to the platelet-derived growth factor family, a peptide corresponding to a part of its constituent or a derivative of these.
Claim 64
Dependent Claim
43 words
A method for controlling antitumor action according to claim 61, wherein the compound belonging to the platelet-derived growth factor family, the peptide corresponding to a part of its constituent or the derivative of these is fibroblast cell growth factor (hereinafter written as FGF).
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