公开(公告)号：US10233197B2

公开(公告)日：2019-03-19

申请号：US13550361

申请日：2012-07-16

申请人： Chongxi Yu

发明人： Chongxi Yu

IPC分类号： C07D501/16 ,  C07D501/18 ,  A61K31/545 ,  A61P31/04 ,  C07D499/00

摘要： The invention provides compositions of novel high penetration compositions (HPC) or high penetration prodrugs (HPP) of antimicrobials and antimicrobial-related compounds, which are capable of crossing biological barriers with high penetration efficiency. The HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

公开(公告)号：US20100172960A1

公开(公告)日：2010-07-08

申请号：US12663262

申请日：2007-06-04

申请人： Chongxi Yu ,  Lina Xu

发明人： Chongxi Yu ,  Lina Xu

IPC分类号： A61K31/397 ,  C07D229/00 ,  C07D405/02 ,  C07D513/04 ,  A61K9/70 ,  A61P17/00

CPC分类号： C07D513/04 ,  C07D205/04 ,  C07D211/22 ,  C07D295/088 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  C07D487/04 ,  C07D491/052

摘要： The novel positively charged pro-drugs of NSAIAs in the general formulas (1, 2a, 2b, 2c, or 2d) “Structure 1, 2a, 2b, 2c, or 2d” were designed and synthesized. The compounds of the general formulas (1, 2a, 2b, 2c, or 2d) “Structure 1, 2a, 2b, 2c, or 2d” indicated above can be prepared from metal salts, organic base salts, or immobilized base salts of NSAIAs with suitable halide compounds. The positively charged amino groups in the pro-drugs in this invention largely increase the solubility of the drugs in water and will bond to the negative charge on the phosphate head group of membrane. Thus, the local concentration of the outside of the membrane or skin will be very high and will facilitate the passage of these pro-drugs from a region of high concentration to a region of low concentration. This bonding will disturb the membrane a little bit and may make some room for the lipophilic portion of the pro-drug. When the molecules of membrane move, the membrane may “crack” a little bit due to the bonding of the pro-drug. This will let the pro-drug insert into the membrane. At pH 7.4, only about 99% of the amino group is protonated. When the amino group is not protonated, the bonding between the amino group of the pro-drug and the phosphate head group of the membrane will disassociate, and the pro-drug will enter the membrane completely. When the amino group of the pro-drug flips to the other side of the membrane and thus becomes protonated, then the pro-drug is pulled into the cytosol, a semi-liquid concentrated aqueous solution or suspension. These pro-drugs can be used for treating and preventing diabetes (type I or/and type II), abnormal blood glucose and lipid levels, stroke, heart attack, and other heart and vascular diseases Alzheimer's diseases, Parkinson's diseases and other neurodegenerative diseases, psoriasis, discoid lupus erythematosus, systemic lupus erythematosus (SLE), autoimmune hepatitis, multiple sclerosis (MS), and other autoimmune diseases, amyotrophic lateral sclerosis (ALS), oculopharyngeal muscular dystrophy (OPMD), and other muscle disorders, inflamed hemorrhoids, cryptitis, other inflammatory conditions of the anorectum, and pruritus ani, prostatitis, prostatocystitis, varicose veins, autoimmune liver inflammation, autoimmune kidney inflammation, vein inflammation and other inflammations, skin cancers, breast cancer, colon-rectum cancer, oral cancer, and other cancers, scars, abnormal vascular skin lesions, birthmarks, moles (nevi), skin tags, aging spots (liver spots), and other skin disorders. These pro-drugs can be administered transdermally without the help of skin penetration enhancers.

公开(公告)号：US20100069336A1

公开(公告)日：2010-03-18

申请号：US12418564

申请日：2009-04-03

申请人： Chongxi Yu ,  Lina Xu

发明人： Chongxi Yu ,  Lina Xu

IPC分类号： A61K31/661 ,  A61P35/00

CPC分类号： C07C233/47 ,  C07C229/42 ,  C07F9/242 ,  C07F9/2429 ,  C07F9/2458

摘要： The invention provides compositions of novel high penetration compositions (HPC) or high penetration prodrugs (HPP) of mustards and mustard-related compounds, which are capable of crossing biological barriers with high penetration efficiency. The HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

摘要翻译： 本发明提供能够穿过具有高穿透效率的生物屏障的芥末和芥菜相关化合物的新型高渗透组合物（HPC）或高渗透前药（HPP）的组合物。 HPP在穿过生物屏障后能够转化为亲本活性药物或药物代谢物，因此可以对母体药物或代谢物可以进行的处理。 此外，HPP能够达到母体药物可能无法进入或在目标区域提供足够浓度的区域，从而进行新的治疗。 HPP可以通过各种施用途径施用于受试者，例如局部递送至具有高浓度或系统地施用于生物受试者的病症的作用部位并以更快的速率进入总体循环。

公开(公告)号：US20100040548A1

公开(公告)日：2010-02-18

申请号：US12482373

申请日：2009-06-10

申请人： Chongxi Yu

发明人： Chongxi Yu

IPC分类号： A61K49/00 ,  C07D499/00 ,  C07D501/00 ,  A61K31/431 ,  A61K31/546 ,  A61K31/5365 ,  C07D498/02 ,  C07D463/00 ,  A61K31/397 ,  A61K31/407 ,  C07D471/04 ,  C07C69/76 ,  A61K31/66

CPC分类号： C07D499/00 ,  A61P31/04

摘要： The invention provides compositions of novel high penetration compositions (HPC) or high penetration prodrugs (HPP) of antimicrobials and antimicrobial-related compounds, which are capable of crossing biological barriers with high penetration efficiency. The HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

摘要翻译： 本发明提供能够跨越具有高穿透效率的生物屏障的新型高渗透组合物（HPC）或抗高血压前药（HPP）的抗微生物剂和抗微生物相关化合物的组合物。 HPP在穿过生物屏障后能够转化为亲本活性药物或药物代谢物，因此可以对母体药物或代谢物可以进行的处理。 此外，HPP能够达到母体药物可能无法进入或在目标区域提供足够浓度的区域，从而进行新的治疗。 HPP可以通过各种施用途径施用于受试者，例如局部递送至具有高浓度或系统地施用于生物受试者的病症的作用部位并以更快的速率进入总体循环。

公开(公告)号：US11541029B2

公开(公告)日：2023-01-03

申请号：US13133021

申请日：2009-12-04

申请人： Chongxi Yu

发明人： Chongxi Yu

IPC分类号： C07C15/30 ,  C07C15/38 ,  A61K8/31 ,  A61K31/015 ,  A61K31/352 ,  C07D215/18 ,  A61K47/54 ,  C07D209/42 ,  C07D295/088 ,  C07D211/34 ,  C07D231/14 ,  C07D313/14 ,  C07D417/04 ,  C07D491/048 ,  C07D501/22 ,  C07D277/56 ,  C07D207/34

摘要： High penetration compositions (HPC) of a parent compound, which are capable of crossing biological barriers with high penetration efficiency. The HPCs are capable of being converted to parent drugs or parent drug-related compounds such as metabolites after crossing one or more biological barriers and thus can render treatments for the conditions that the parent drugs or parent drug-related compounds can. Additionally, the HPCs are capable of reaching areas that their parent drugs or parent drug-related compounds may not be able to access or to render a sufficient concentration at the target areas HPCs of NSAIA, for example, have demonstrated indications such as treating hair loss. A HPC can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

公开(公告)号：US10189774B2

公开(公告)日：2019-01-29

申请号：US12418564

申请日：2009-04-03

申请人： Chongxi Yu ,  Lina Xu

发明人： Chongxi Yu ,  Lina Xu

IPC分类号： A61K31/661 ,  A61P35/00 ,  C07C233/47 ,  C07C229/42 ,  C07F9/24

摘要： The invention provides compositions of novel high penetration compositions (HPC) or high penetration prodrugs (HPP) of mustards and mustard-related compounds, which are capable of crossing biological barriers with high penetration efficiency. The HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

公开(公告)号：US20100010084A1

公开(公告)日：2010-01-14

申请号：US12503739

申请日：2009-07-15

申请人： Chongxi Yu

发明人： Chongxi Yu

IPC分类号： A61K31/24 ,  A61K31/20 ,  A61K31/19 ,  A61K31/22 ,  A61K31/15 ,  A61K31/13 ,  C12Q1/02 ,  A61P17/00 ,  A61P27/02 ,  A61P35/04

CPC分类号： A61K47/48023 ,  A61K31/21 ,  A61K31/215 ,  A61K31/216 ,  A61K31/221 ,  A61K31/4453 ,  A61K47/54 ,  C07C219/10 ,  C07C2601/16 ,  C07C2602/10 ,  G01N33/502

摘要： The invention provides compositions of novel high penetration compositions (HPC) or high penetration prodrugs (HPP) of retinoids and retinoid-related compounds, which are capable of crossing biological barriers with high penetration efficiency. The HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

摘要翻译： 本发明提供了能够穿过具有高穿透效率的生物屏障的类视黄醇和类视黄醇相关化合物的新型高渗透组合物（HPC）或高渗透前药（HPP）的组合物。 HPP在穿过生物屏障后能够转化为亲本活性药物或药物代谢物，因此可以对母体药物或代谢物可以进行的处理。 此外，HPP能够达到母体药物可能无法进入或在目标区域提供足够浓度的区域，从而进行新的治疗。 HPP可以通过各种施用途径施用于受试者，例如局部递送至具有高浓度或系统地施用于生物受试者的病症的作用部位并以更快的速率进入总体循环。

公开(公告)号：US20090311184A1

公开(公告)日：2009-12-17

申请号：US12463374

申请日：2009-05-08

申请人： Chongxi Yu

发明人： Chongxi Yu

IPC分类号： A61K49/00 ,  C07K7/06 ,  A61K38/08 ,  C12Q1/02 ,  A61K9/12

CPC分类号： C07C317/28 ,  A61K9/0014 ,  A61K31/145 ,  A61K31/222 ,  A61K31/40 ,  A61K31/4184 ,  A61K47/54 ,  C07C323/58 ,  C07D403/12 ,  C07D403/14 ,  C07K5/1016 ,  C07K7/56

摘要： The invention provides compositions of novel high penetration compositions (HPC) or high penetration prodrugs (HPP) of peptides and peptide-related compounds, which are capable of crossing biological barriers with high penetration efficiency. The HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

摘要翻译： 本发明提供了能够穿过具有高穿透效率的生物屏障的肽和肽相关化合物的新型高渗透组合物（HPC）或高渗透前药（HPP）的组合物。 HPP在穿过生物屏障后能够转化为亲本活性药物或药物代谢物，因此可以对母体药物或代谢物可以进行的处理。 此外，HPP能够达到母体药物可能无法进入或在目标区域提供足够浓度的区域，从而进行新的治疗。 HPP可以通过各种施用途径施用于受试者，例如局部递送至具有高浓度或系统地施用于生物受试者的病症的作用部位并以更快的速率进入总体循环。

公开(公告)号：US20090221703A1

公开(公告)日：2009-09-03

申请号：US12397308

申请日：2009-03-03

申请人： Chongxi Yu ,  Lina Xu

发明人： Chongxi Yu ,  Lina Xu

IPC分类号： A61K31/22 ,  C07C229/02 ,  A61P37/06 ,  A61P29/00 ,  A61P25/00

CPC分类号： A61K9/0014 ,  A61K9/7023 ,  A61K31/167 ,  A61K31/22 ,  A61K31/612 ,  A61K47/54 ,  A61K47/542 ,  C07C231/12 ,  C07C233/25

摘要： The present invention relates to compositions and uses of novel high penetration compositions or high penetration prodrugs (HPP), in particular HPPs for 4-aminophenol derivatives, which are capable of crossing biological barriers with high penetration efficiency. The HPPs herein are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, due to the ability of penetrating biological barriers, the HPPs herein are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPPs herein can be administered to a subject through various administration routes. For example, the HPPs can be locally delivered to an action site of a condition with a high concentration due to their ability of penetrating biological barriers and thus obviate the need for a systematic administration. For another example, the HPPs herein can be systematically administer to a biological subject and enter the general circulation with a faster rate.

摘要翻译： 本发明涉及新型高渗透组合物或高渗透性前药（HPP），特别是4-氨基苯酚衍生物的HPP的组合物和用途，其能够穿透具有高穿透效率的生物屏障。 本文中的HPP能够在穿过生物屏障之后转化为亲本活性药物或药物代谢物，因此可以对母体药物或代谢物可以进行的处理。 此外，由于穿透生物屏障的能力，本文的HPP能够达到母体药物可能无法进入或在目标区域呈现足够浓度的区域，因此进行新的治疗。 这里的HPP可以通过各种管理途径施用于受试者。 例如，HPP可以由于其穿透生物屏障的能力而被局部递送到具有高浓度的病症的动作部位，从而避免了对系统性给药的需要。 另一个例子，这里的HPP可以系统地施用于生物受试者并以更快的速率进入总体循环。

公开(公告)号：US09193672B2

公开(公告)日：2015-11-24

申请号：US12503739

申请日：2009-07-15

申请人： Chongxi Yu

发明人： Chongxi Yu

IPC分类号： A61K31/24 ,  A61K31/20 ,  A61K31/19 ,  A61K31/22 ,  A61K31/15 ,  A61K31/13 ,  C12Q1/02 ,  A61P17/00 ,  A61P27/02 ,  A61P35/04 ,  C07C219/10

CPC分类号： A61K47/48023 ,  A61K31/21 ,  A61K31/215 ,  A61K31/216 ,  A61K31/221 ,  A61K31/4453 ,  A61K47/54 ,  C07C219/10 ,  C07C2601/16 ,  C07C2602/10 ,  G01N33/502

摘要： The invention provides compositions of novel high penetration compositions (HPC) or high penetration prodrugs (HPP) of retinoids and retinoid-related compounds, which are capable of crossing biological barriers with high penetration efficiency. The HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

摘要翻译： 本发明提供了能够穿过具有高穿透效率的生物屏障的类视黄醇和类视黄醇相关化合物的新型高渗透组合物（HPC）或高渗透前药（HPP）的组合物。 HPP在穿过生物屏障后能够转化为亲本活性药物或药物代谢物，因此可以对母体药物或代谢物可以进行的处理。 此外，HPP能够达到母体药物可能无法进入或在目标区域提供足够浓度的区域，从而进行新的治疗。 HPP可以通过各种施用途径施用于受试者，例如局部递送至具有高浓度或系统地施用于生物受试者的病症的作用部位并以更快的速率进入总体循环。