公开(公告)号：US11865101B2

公开(公告)日：2024-01-09

申请号：US17307208

申请日：2021-05-04

申请人： Vilmali Lopez-Mejias ,  Jeaninna P. Flores Bello ,  Israel Rodriguez Rodriguez ,  Joyce Marie Serrano Valcarcel

发明人： Vilmali Lopez-Mejias ,  Jeaninna P. Flores Bello ,  Israel Rodriguez Rodriguez ,  Joyce Marie Serrano Valcarcel

IPC分类号： A61K31/352

CPC分类号： A61K31/352 ,  C07B2200/13

摘要： A series of pharmaceutical metal complexes (pMCs) were produced and characterized using the mast cell stabilizer, cromolyn, and bioactive metal ions (Zn+2, Mg+2, and Ca+2). Three novel pMCs, Cromolyn-Zn, Cromolyn-Mg, and Cromolyn-Ca were formed through reactions under controlled temperature and pH conditions. TGA demonstrated that these metal complexes showed an enhanced thermal stability due to the strong coordination with the ligand, cromolyn. PXRD data indicates a high degree of crystallinity as well as a unique packing arrangement for each pMCs. SEM analysis showed materials with well-defined morphologies while EDS presented elemental evidence for the unique composition of each pMCs. The crystal structure for these materials was elucidated through SCXRD, and a variety of binding modes and packing motifs were found within each respective metal complex. Only 2D structures were achieved under the conditions studied. Dissolution studies show high stability and slow degradation for the metal complexes, while a higher dissolution was observed for the drug compound in PBS. Neither CS nor the pMCs dissolved significantly in FaSSGF at 37° C.

公开(公告)号：US20210317149A1

公开(公告)日：2021-10-14

申请号：US17228629

申请日：2021-04-12

申请人： Vilmali Lopez-Mejias ,  Lesly Y. Carmona-Sarabia ,  Andrea M. Escalera Joy ,  Darilys Mojica Vazquez

发明人： Vilmali Lopez-Mejias ,  Lesly Y. Carmona-Sarabia ,  Andrea M. Escalera Joy ,  Darilys Mojica Vazquez

IPC分类号： C07F9/38

摘要： The invention provides extended bisphosphonate-based metal complexes using benzene1,4-bis(bisphosphonic acid) (BBPA), an analog of benzene 1,4-dicarboxylic acid (BDC). Hydrothermal synthesis of BBPA with the bioactive metals Ca2+, Zn2+, and Mg2+ leads to four crystals phases, namely, BBPA-Ca forms I and II, BBPA-Zn form I, and BBPA-Mg form I. Out of the three structures, BBPA-Ca form II presents large channels (8 Å×12 Å), potentiating the use of this framework to load drugs. Dissolution profiles were conducted to investigate the release of BBPA from BBPA-based metal complexes under physiological conditions (phosphate-buffered saline, PBS). These results show that 200 μM at 24, 48, and 72 h of treatment. The BBPA in the range of concentration employed (0-200 μM) was no cytotoxic against these cell lines.

公开(公告)号：US11713331B2

公开(公告)日：2023-08-01

申请号：US17228629

申请日：2021-04-12

申请人： Vilmali Lopez-Mejias ,  Lesly Y. Carmona-Sarabia ,  Andrea M. Escalera Joy ,  Darilys Mojica Vazquez

发明人： Vilmali Lopez-Mejias ,  Lesly Y. Carmona-Sarabia ,  Andrea M. Escalera Joy ,  Darilys Mojica Vazquez

IPC分类号： C07F9/38

CPC分类号： C07F9/386 ,  C07B2200/13

摘要： The invention provides extended bisphosphonate-based metal complexes using benzene1,4-bis(bisphosphonic acid) (BBPA), an analog of benzene 1,4-dicarboxylic acid (BDC). Hydrothermal synthesis of BBPA with the bioactive metals Ca2+, Zn2+, and Mg2+ leads to four crystals phases, namely, BBPA-Ca forms I and II, BBPA-Zn form I, and BBPA-Mg form I. Out of the three structures, BBPA-Ca form II presents large channels (8 Å×12 Å), potentiating the use of this framework to load drugs. Cytotoxicity effects of BBPA was elucidated in a human breast cancer MDA-MB-231 and a normal osteoblast hFOB 1.19 cell lines. The half-maximal inhibitory concentration (IC50) for BBPA used to treat both cell lines were >200 μM at 24, 48, and 72 h of treatment. The BBPA in the range of concentration employed (0-200 μM) was not cytotoxic against these cell lines.

公开(公告)号：US20240082210A1

公开(公告)日：2024-03-14

申请号：US18515252

申请日：2023-11-20

申请人： Vilmali Lopez-Mejias ,  Jeaninna P. Flores Bello ,  Israel Rodriguez Rodriguez ,  Joyce Marie Serrano Valcarcel

发明人： Vilmali Lopez-Mejias ,  Jeaninna P. Flores Bello ,  Israel Rodriguez Rodriguez ,  Joyce Marie Serrano Valcarcel

IPC分类号： A61K31/352

CPC分类号： A61K31/352 ,  C07B2200/13

摘要： A series of pharmaceutical metal complexes (pMCs) were produced and characterized using the mast cell stabilizer, cromolyn, and bioactive metal ions (Zn+2, Mg+2, and Ca+2). Three novel pMCs, Cromolyn-Zn, Cromolyn-Mg, and Cromolyn-Ca were formed through reactions under controlled temperature and pH conditions. TGA demonstrated that these metal complexes showed an enhanced thermal stability due to the strong coordination with the ligand, cromolyn. PXRD data indicates a high degree of crystallinity as well as a unique packing arrangement for each pMCs. SEM analysis showed materials with well-defined morphologies while EDS presented elemental evidence for the unique composition of each pMCs. The crystal structure for these materials was elucidated through SCXRD, and a variety of binding modes and packing motifs were found within each respective metal complex. Only 2D structures were achieved under the conditions studied. Dissolution studies show high stability and slow degradation for the metal complexes, while a higher dissolution was observed for the drug compound in PBS. Neither CS nor the pMCs dissolved significantly in FaSSGF at 37° C.

公开(公告)号：US20210338628A1

公开(公告)日：2021-11-04

申请号：US17307208

申请日：2021-05-04

申请人： Vilmali Lopez-Mejias ,  Jeaninna P. Flores Bello ,  Israel Rodriguez Rodriguez ,  Joyce Marie Serrano Valcarcel

发明人： Vilmali Lopez-Mejias ,  Jeaninna P. Flores Bello ,  Israel Rodriguez Rodriguez ,  Joyce Marie Serrano Valcarcel

IPC分类号： A61K31/315 ,  A61K31/352

摘要： A series of pharmaceutical metal complexes (pMCs) were produced and characterized using the mast cell stabilizer, cromolyn, and bioactive metal ions (Zn+2, Mg+2, and Ca+2). Three novel pMCs, Cromolyn-Zn, Cromolyn-Mg, and Cromolyn-Ca were formed through reactions under controlled temperature and pH conditions. TGA demonstrated that these metal complexes showed an enhanced thermal stability due to the strong coordination with the ligand, cromolyn. PXRD data indicates a high degree of crystallinity as well as a unique packing arrangement for each pMCs. SEM analysis showed materials with well-defined morphologies while EDS presented elemental evidence for the unique composition of each pMCs. The crystal structure for these materials was elucidated through SCXRD, and a variety of binding modes and packing motifs were found within each respective metal complex. Only 2D structures were achieved under the conditions studied. Dissolution studies show high stability and slow degradation for the metal complexes, while a higher dissolution was observed for the drug compound in PBS. Neither CS nor the pMCs dissolved significantly in FaSSGF at 37° C.

公开(公告)号：US10479808B1

公开(公告)日：2019-11-19

申请号：US16271754

申请日：2019-02-08

申请人： Vilmali Lopez-Mejias ,  Gabriel Quinonez-Velez ,  Waldemar Amaury Rodriguez-Silva

发明人： Vilmali Lopez-Mejias ,  Gabriel Quinonez-Velez ,  Waldemar Amaury Rodriguez-Silva

IPC分类号： C07F9/38 ,  C07F3/02

摘要： The hydrothermal reaction between bioactive metals (Ca2+, Zn2+, and Mg2+) salts and clinically utilized bisphosphonate (BP) alendronic acid (ALEN) were performed to prepare several bisphosphonate-based biocompatible coordination complexes (pBioCCs). The invention describes the effect of three variables M2+/BP molar ratio, reaction temperature, and pH on the reaction outcomes yields an unprecedented number of crystalline materials of enough crystal quality for structural elucidation. The crystal structure was unveiled by single crystal X-ray diffraction at 100 K and their solid-state properties revealed in tandem with other characterization techniques: thermogravimetry, vibrational spectroscopy, and elemental analysis. The invention provides materials with high structural stability and dissolution properties paving the way for better formulation strategies for alendronic acid (ALEN) through the design of pBioCCs for the treatment of bone-related diseases.