Treatments employing drug containing matrices for introduction into cellular lesion areas

Abstract

Treatment of cellular disorders involving abnormal solid cellular growths involves introduction of cytotoxic reagents dispersed in a physiologically acceptable proteinaceous matrix into the solid cellular growth or area of an existing or removed solid cellular growth. Enhanced effectiveness of the drug is observed, with reduced cytotoxic effects on cells distant from the site of introduction. Other drugs may be included to enhance therapeutic gain and reduce adverse affects to normal tissue.

What is claimed is: 
     
       1. A proteinaceous composition comprising from 30% to 95% of collagen and/or fibrinogen dispersed in an aqueous medium as an amorphous flowable mass at a concentration of from about 5 to 75 mg/ml and from about 0.1 to 50 weight percent based on said collagen and/or fibrinogen of a cytotoxic drug .Iadd.or proliferation inhibitor.Iaddend..Badd., wherein when said proteinaceous composition comprises collagen, said collagen is present as a uniform dispersion of collagen fibrils.Baddend.. 2. A composition according to claim 1, wherein said cytotoxic drug is cis-platinum, adriamycin, bleomycin, 5-fluorouracil or vincristine. 3. A .Badd.proteinaceous .Baddend.composition . .. .according to claim 1, having.!..!. .Badd.comprising from 30% to 95% of collagen and/or fibrinogen dispersed in an aqueous medium as an amorphous flowable mass at a concentration of from about 5 to 75 mg/ml; from about 0.1 to 50 weight percent based on said collagen and/or fibrinogen of a cytotoxic drug or proliferation inhibitor and .Baddend.a vasoconstrictive amount of a vasoconstrictive drug. 4. A composition according to claim 3, wherein said . .. .vasoconstrictor.!..!. .Badd.vasoconstrictive .Baddend.drug is epinephrine or nor-epinephrine. 5. A method for treating a neoplastic .Iadd.or hyperproliferative .Iaddend.lesion or surrounding tissue which comprises: introducing at the site of said lesion a proteinaceous matrix composition capable of stable placement, consisting essentially . .or.!. .Iadd.of a .Iaddend.physiologically acceptable matrix forming collagen, fibrinogen or combination thereof, dispersed in an aqueous medium as an amorphous flowable mass including at least one cytotoxic drug .Iadd.or proliferation inhibitor .Iaddend.uniformly dispersed in said composition. .;.!.. .. .:.!..!..Badd.;.Baddend.   whereby said . .. .drug.!..!. .Badd.cytotoxic drug or proliferation inhibitor .Baddend.is slowly released into the . .. .immediate environment.!..!. .Badd.neoplastic or hyperproliferative lesion or surrounding tissue .Baddend.avoiding significant levels of . .. .the drug.!..!. .Badd.said cytotoxic drug or proliferation inhibitor .Baddend.at sites distant from the site of introduction. 6. A method according to claim 5, wherein said proteinaceous composition is a collagen fibril dispersion. 7. A method according to claim 6, wherein said . .. .drug.!..!. .Badd.cytotoxic drug or proliferation inhibitor .Baddend.is at least one of cis-platinum, adriamycin, . .. .5fluorouracil.!..!. .Badd.5-fluorouracil.Baddend., bleomycin, vincristine, or methotrexate. 8. A method according to claim 7, wherein said composition includes a sufficient amount of a . .. .vasoconstrictor.!..!. .Badd.vasoconstrictive drug .Baddend.to constrict capillaries in the vicinity of said lesion. 9. A method according to claim 8, wherein said . .. .vasoconstrictor.!..!. .Badd.vasoconstrictive drug .Baddend.is epinephrine or nor-epinephrine. 10. A method according to claim 7, wherein said . .. .drug.!..!. .Badd.cytotoxic drug or proliferation inhibitor .Baddend.is cis-platinum. 11. A method according to claim 7, wherein said . .. .drug.!..!. .Badd.cytotoxic drug or proliferation inhibitor .Baddend.is   
     
     
        5-fluorouracil. 12. A method according to claim 5, comprising the additional step of treating said lesion . .. .size.!..!. .Badd.site .Baddend.with radiation or heat. .Iadd.13. A proteinaceous composition comprising from 30% to 95% of collagen and/or fibrinogen dispersed in an aqueous medium as an amorphous flowable mass at a concentration of from about 5 to 75 mg/ml and from about 0.1 to 50 weight percent based on said collagen and/or fibrinogen of a cytotoxic drug.Iaddend..Badd., wherein when said proteinaceous composition comprises collagen, said collagen is present as a uniform dispersion of collagen fibrils. .Baddend..Iadd.14. A proteinaceous composition comprising from 30% to 95% of collagen and/or fibrinogen dispersed in an aqueous medium as an amorphous flowable mass at a concentration of from about 5 to 75 mg/ml and from about 0.1 to 50 weight percent based on said collagen and/or fibrinogen of a proliferation inhibitor.Iaddend..Badd., wherein when said proteinaceous composition comprises collagen, said collagen is present as a uniform dispersion of collagen fibrils. .Baddend..Iadd.15. A method for treating a neoplastic lesion or surrounding tissue which comprises: introducing at the site of said lesion a proteinaceous matrix composition capable of stable placement consisting essentially of a physiologically acceptable matrix forming collagen, fibrinogen or combination thereof, dispersed in an aqueous medium as an amorphous flowable mass, including at least one cytotoxic drug or proliferation inhibitor uniformly dispersed in said composition;   whereby said .Iadd.. .. .drug.!..!..Iaddend. .Badd.cytotoxic drug or proliferation inhibitor .Baddend..Iadd.is slowly released into the .Iadd.. .. .immediate environment.!..!..Iaddend. .Badd.neoplastic lesion or surrounding tissue .Baddend..Iadd.avoiding significant levels of .Iaddend..Iadd.. .. .the drug.!..!..Iaddend. .Badd.said cytotoxic drug or proliferation inhibitor .Baddend..Iadd.at sites distant from the site of   
     
     
        introduction. .Iaddend..Iadd.16.  A method for treating a hyperproliferative lesion or surrounding tissue which comprises: introducing at the site of said lesion a proteinaceous matrix composition capable of stable placement consisting essentially of a physiologically acceptable matrix forming collagen, fibrinogen or combination thereof, dispersed in an aqueous medium as an amorphous flowable mass, including at least one cytotoxic drug or proliferation inhibitor uniformly dispersed in said composition;   whereby said .Iaddend..Iadd.. .. .drug.!..!..Iaddend. .Badd.cytotoxic drug or proliferation inhibitor .Baddend..Iadd.is slowly released into the .Iadd.. .. .immediate environment.!..!..Iaddend. .Badd.hyperproliferative lesion or surrounding tissue .Baddend..Iadd.avoiding significant levels of .Iaddend..Iadd.. .. .the drug.!..!..Iaddend. .Badd.said cytotoxic drug or proliferation inhibitor .Baddend..Iadd.at sites distant from the site of introduction. .Iaddend.