# US 12,178,794 B2 · Isothiocyanate functional compounds augmented with secondary antineoplastic medicaments and associated methods for treating neoplasms > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,178,794 B2 - Document ID: US12178794B2 - Status: Granted - Kind: B2 - Application number: 18/074,711 - Filed: 2022-12-05 - Published: 2023-06-01 - Granted: 2024-12-31 - Earliest claimed: 2012-07-26 - Assignees: The William Yarbrough Foundation - Applicants: The William M Yarbrough Foundation - Inventors: Michael E. Silver - Web page: https://patentgrep.com/patent/US12178794B2 ## CPC - A61K 31/26: Cyanate or isocyanate esters; Thiocyanate or isothiocyanate esters - A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)} - A61K 31/16: Amides, e.g. hydroxamic acids - A61K 31/195: having an amino group - A61K 31/198: Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00) - A61K 31/277: having a ring, e.g. verapamil - A61K 31/513: having oxo groups directly attached to the heterocyclic ring, e.g. cytosine - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 35/00: Antineoplastic agents - A61K 9/00: Medicinal preparations characterised by special physical form {(nuclear magnetic resonance contrast preparations or magnetic resonance imaging contrast preparations A61K49/18; preparations containing radioactive substances A61K51/12)} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract A formulation, including: (a) a first medicament, wherein the first medicament includes an isothiocyanate functional compound/surfactant; and (b) a second medicament, wherein the second medicament includes an antineoplastic agent, such as a cytotoxic antineoplastic agent and/or a targeted antineoplastic agent. ## Claims ### Claim 1 A medicament formulation, comprising: a first medicament, wherein the first medicament comprises an isothiocyanate functional surfactant; a second medicament, wherein the second medicament comprises an antineoplastic agent; and wherein the weight ratio of the first medicament to the second medicament is in a range of about 1:10 to 10:1. ### Claim 2 (depends on 1) The medicament formulation according to claim 1, wherein the isothiocyanate functional surfactant comprises at least one isothiocyanate functional group associated with an aliphatic and/or aromatic carbon atom of the isothiocyanate functional surfactant. ### Claim 3 (depends on 1) The medicament formulation according to claim 1, wherein the isothiocyanate functional surfactant comprises a lysine derivative, wherein the lysine derivative comprises an α-nitrogen and a ε-nitrogen, and wherein an alkyl and/or alkanoyl substituent comprising at least approximately 8 carbon atoms is associated with the α-nitrogen, and further wherein at least one isothiocyanate functional group is associated with the ε-nitrogen. ### Claim 4 (depends on 1) The medicament formulation according to claim 1, wherein the isothiocyanate functional surfactant is represented by the following chemical structure: wherein a protonated form of the isothiocyanate functional surfactant comprises a non-polar moiety (NP) and a polar moiety (P), and wherein at least one isothiocyanate functional group (NCS) is associated with the polar moiety (P), the non-polar moiety (NP), or both the polar moiety (P) and the non-polar moiety (NP). ### Claim 5 (depends on 1) The medicament formulation according to claim 1, wherein a protonated form of the isothiocyanate functional surfactant is represented by the following chemical structure: wherein R1 comprises an alkyl, cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkanoyl, aroyl, alkenyl, alkynyl and/or cyano group containing approximately 1 to approximately 25 carbon atom(s), wherein the carbon atom(s) may be a linking group to, or part of, a halogen, a N, O, and/or S containing moiety, and/or one or more functional groups comprising alcohols, esters, ammonium salts, phosphonium salts, and combinations thereof; a linkage to a dimer; a linkage to an oligomer; and/or a linkage to a polymer; wherein R2 comprises NCS; and wherein R3-R5 are the same or different and comprise H; OH; an alkyl, cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkanoyl, aroyl, alkenyl, alkynyl and/or cyano group containing approximately 1 to approximately 25 carbon atom(s), wherein the carbon atom(s) may be a linking group to, or part of, a halogen, a N, O, and/or S containing moiety, and/or one or more functional groups comprising alcohols, esters, ammonium salts, phosphonium salts, and combinations thereof; a linkage to a dimer; a linkage to an oligomer; and/or a linkage to a polymer with the proviso that at least one of R3-R5 comprise an alkyl, cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkanoyl, aroyl, alkenyl, alkynyl and/or cyano group containing approximately 8 to approximately 25 carbon atom(s). ### Claim 6 (depends on 1) The medicament formulation according to claim 1, wherein a protonated form of the isothiocyanate functional surfactant is represented by the following chemical structure: wherein R1 is selected from the group consisting of an alkyl group containing 1 to 25 carbon atom(s); wherein R2 is selected from the group consisting of NCS; and wherein R3-R5 are each independently selected from the group consisting of H; OH; and an alkyl, and alkanoyl group containing 1 to 25 carbon atom(s) with the proviso that at least one of R3-R5 is selected from the group consisting of an alkyl, and alkanoyl, group containing 8 to 25 carbon atoms. ### Claim 7 (depends on 1) The medicament formulation according to claim 1, wherein a protonated form of the isothiocyanate functional surfactant is represented by the following chemical structure: wherein X comprises an integer ranging from approximately 1 to approximately 25, and wherein Y comprises an integer ranging from approximately 6 to approximately 25. ### Claim 8 (depends on 1) The medicament formulation according to claim 1, wherein a protonated form of the isothiocyanate functional surfactant is represented by the following chemical structure: ### Claim 9 (depends on 1) The medicament formulation according to claim 1, wherein a protonated form of the isothiocyanate functional surfactant is represented by at least one of the following chemical structures: ### Claim 10 (depends on 1) The medicament formulation according to claim 1, wherein the isothiocyanate functional surfactant is represented by the following chemical structure: wherein R1 comprises an alkyl, cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkanoyl, aroyl, alkenyl, alkynyl and/or cyano group containing approximately 1 to approximately 25 carbon atom(s), wherein the carbon atom(s) may be a linking group to, or part of, a halogen, a N, O, and/or S containing moiety, and/or one or more functional groups comprising alcohols, esters, ammonium salts, phosphonium salts, and combinations thereof; a linkage to a dimer; a linkage to an oligomer; and/or a linkage to a polymer; wherein R2 comprises NCS; wherein R3-R5 are the same or different and comprise H; OH; an alkyl, cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkanoyl, aroyl, alkenyl, alkynyl and/or cyano group containing approximately 1 to approximately 25 carbon atom(s), wherein the carbon atom(s) may be a linking group to, or part of, a halogen, a N, O, and/or S containing moiety, and/or one or more functional groups comprising alcohols, esters, ammonium salts, phosphonium salts, and combinations thereof; a linkage to a dimer; a linkage to an oligomer; and/or a linkage to a polymer with the proviso that at least one of R3-R5 comprise an alkyl, cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkanoyl, aroyl, alkenyl, alkynyl and/or cyano group containing approximately 8 to approximately 25 carbon atom(s), wherein X comprises a counter cation such as, but not limited to, alkali metals, alkaline earth metals, transition metals, s-block metals, d-block metals, p-block metals, NZ4+, wherein Z comprises, H, R6, OR6, and wherein R6 comprises an alkyl, cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkanoyl, aroyl, alkenyl, alkynyl and/or cyano group containing approximately 1 to approximately 25 carbon atom(s), wherein the carbon atom(s) may be a linking group to, or part of, a halogen, a N, O, and/or S containing moiety, and/or one or more functional groups comprising alcohols, esters, ammonium salts, phosphonium salts, and combinations thereof; a linkage to a dimer; a linkage to an oligomer; and/or a linkage to a polymer. ### Claim 11 (depends on 1) The medicament formulation according to claim 1, wherein the isothiocyanate functional surfactant is represented by the following chemical structure: wherein R1 is selected from the group consisting of an alkyl group containing 1 to 25 carbon atom(s); wherein R2 is selected from the group consisting of NCS; and wherein R3-R5 are each independently selected from the group consisting of H; OH; and an alkyl, and alkanoyl group containing 1 to 25 carbon atom(s) with the proviso that at least one of R3-R5 is selected from the group consisting of an alkyl, and alkanoyl, group containing 8 to 25 carbon atoms; and wherein X comprises a counter cation. ### Claim 12 (depends on 1) The medicament formulation according to claim 1, wherein the second medicament comprises at least one of a cytotoxic antineoplastic agent and a targeted antineoplastic agent. ### Claim 13 (depends on 1) The medicament formulation according to claim 1, wherein the second medicament comprises a cytotoxic antineoplastic agent that is a nucleoside analogue, an antifolate, an antimetabolite, a topoisomerase inhibitor, an anthracycline, a podophyllotoxin, a taxane, a vinca alkaloid, an alkylating agent, and/or a platinum compound. ### Claim 14 (depends on 1) The medicament formulation according to claim 1, wherein the second medicament comprises a monoclonal antibody, a tyrosine kinase inhibitor, an mTOR inhibitor, a retinoid, an immunomodulatory agent, and/or a histone deacetylase inhibitor. ### Claim 15 (depends on 1) The medicament formulation according to claim 1, wherein the second medicament comprises a DNA-effecting or influencing anti-cancer medicament, a kinase-inhibiting anti-cancer medicament, an anti-androgen medicament and/or a hormonal anti-cancer medicament. ### Claim 16 (depends on 1) The medicament formulation according to claim 1, wherein the second medicament comprises bicalutamide. ### Claim 17 (depends on 1) The medicament formulation according to claim 1, wherein the second medicament comprises fluorouacil. ### Claim 18 (depends on 1) The medicament formulation according to claim 1, wherein the second medicament comprises chlormethine. ### Claim 19 (depends on 1) The medicament formulation according to claim 1, wherein the second medicament comprises at least one of bevacizumab, cetuximab, denosumab, gemtuzumab ozogamicin, ibritumomab tiuxetan, ipilimumab, nivolumab, ofatumumab, panitumumab, pembrolizumab, pertuzumab, rituximab, tositumomab, and trastuzumab. ### Claim 20 (depends on 1) The medicament formulation according to claim 1, wherein the second medicament comprises at least one of alitretinoin, bexarotene, isotretinoin, tamibarotene, and tretinoin.