Abstract

The present disclosure provides 2-(diethylamino)ethyl acetoxybenzoate hydrochloride, other high penetration prodrugs of aspirin and other NSAIDs, and pharmaceutically acceptable salts thereof for use and methods thereof in the prevention or treatment of cardiovascular diseases and conditions. Pharmaceutical compositions, treatment kits and devices including 2-(diethylamino)ethyl acetoxybenzoate hydrochloride, other high penetration prodrugs of aspirin and other NSAIDs, and pharmaceutically acceptable salts thereof, as well as dosage forms, dosages, and methods of use thereof through topical administration are described.

IPC Classes  ?

• A61K 31/606 - Salicylic acidDerivatives thereof having amino groups
• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 31/616 - Salicylic acidDerivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
• A61K 31/625 - Salicylic acidDerivatives thereof having heterocyclic substituents, e.g. 4-salicyloylmorpholine
• A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

IPC Classes  ?

• A61K 31/13 - Amines, e.g. amantadine
• A61P 31/12 - Antivirals
• C07C 211/64 - Quaternary ammonium compounds having quaternised nitrogen atoms bound to carbon atoms of six-membered aromatic rings
• C07D 207/06 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
• C07D 211/12 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with only hydrogen atoms attached to the ring nitrogen atom

Abstract

High penetration prodrugs (HPPs), pharmaceutical compositions and methods thereof, for treatment of signs, symptoms and/or complications of viral, bacterial, protozoal, and/or fungal infections are disclosed. The HPPs are capable of penetrating one or more biological barriers to reach areas that their corresponding parent drugs may not be able to reach with sufficient quantities. While the HPPs can be administered to a subject through various administration routes, e.g., local delivery or systemic administration, transdermal or topical administration of them provides various additional advantages over use of the parent drugs.

IPC Classes  ?

• C07D 211/12 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with only hydrogen atoms attached to the ring nitrogen atom
• C07D 207/06 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
• C07C 211/64 - Quaternary ammonium compounds having quaternised nitrogen atoms bound to carbon atoms of six-membered aromatic rings
• A61K 31/13 - Amines, e.g. amantadine
• A61P 31/12 - Antivirals
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]

Abstract

It provides 2- (diethylamino) ethyl acetoxybenzoate hydrochloride, other high penetration prodrugs of aspirin and other NSAIDs, and pharmaceutically acceptable salts thereof for use and methods thereof in the prevention or treatment of cardiovascular diseases and conditions. Pharmaceutical compositions, treatment kits and devices comprising 2- (diethylamino) ethyl acetoxybenzoate hydrochloride, other high penetration prodrugs of aspirin and other NSAIDs, and pharmaceutically acceptable salts thereof, as well as dosage forms, dosages, and methods of use thereof through topical administration are disclosed.

IPC Classes  ?

• A61K 31/60 - Salicylic acidDerivatives thereof
• A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• C07C 235/42 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton

Abstract

It provides 2- (diethylamino) ethyl acetoxybenzoate hydrochloride, other high penetration prodrugs of aspirin and other NSAIDs, and pharmaceutically acceptable salts thereof for use and methods thereof in the prevention or treatment of cardiovascular diseases and conditions. Pharmaceutical compositions, treatment kits and devices comprising 2- (diethylamino) ethyl acetoxybenzoate hydrochloride, other high penetration prodrugs of aspirin and other NSAIDs, and pharmaceutically acceptable salts thereof, as well as dosage forms, dosages, and methods of use thereof through topical administration are disclosed.

IPC Classes  ?

• A61K 31/60 - Salicylic acidDerivatives thereof
• C07C 235/42 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
• A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

Provided are pharmaceutical compositions comprising at least one high penetration drug (HPD) that has at least one protonated amino group in its molecular and is capable of penetrating across one or more biological barriers in high rates, methods for improving the stability of the pharmaceutical compositions, and methods of using the pharmaceutical compositions for preventing, diagnosing and/or treating condition or disease in human, animals and plants.

IPC Classes  ?

• A61K 9/08 - Solutions
• A61K 47/12 - Carboxylic acidsSalts or anhydrides thereof
• A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

Provided herein is 2-(diethylamino) ethyl 2-(4-isobutylphenyl) propionate or pharmaceutically acceptable salts thereof. Furthermore, for use and methods in the treatment of various pains and inflammation, in particular osteoarthritis with pharmaceutical compositions, treatment kits and devices comprising 2-(diethylamino) ethyl 2-(4-isobutylphenyl) propionate and/or pharmaceutically acceptable salts thereof, as well as dosage forms, dosages, and methods of use thereof through topical administration, for treatment of various pains and inflammation, in particular osteoarthritis, are disclosed.

IPC Classes  ?

• A61K 31/216 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
• A61P 19/02 - Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
• C07C 211/63 - Quaternary ammonium compounds having quaternised nitrogen atoms bound to acyclic carbon atoms
• C07C 213/06 - Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton from hydroxy amines by reactions involving the etherification or esterification of hydroxy groups
• C07C 219/10 - Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having at least one of the hydroxy groups esterified by a carboxylic acid having the esterifying carboxyl group bound to an acyclic carbon atom of a carbon skeleton containing rings

Abstract

Provided are pharmaceutical compositions comprising at least one high penetration drug (HPD) that has at least one protonated amino group in its molecular and is capable of penetrating across one or more biological barriers in high rates, methods for improving the stability of the pharmaceutical compositions, and methods of using the pharmaceutical compositions for preventing, diagnosing and/or treating condition or disease in human, animals and plants.

IPC Classes  ?

• A61K 9/08 - Solutions
• A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups

Abstract

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. W hen 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.

IPC Classes  ?

• C07D 209/32 - Oxygen atoms
• C07D 231/12 - Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• C07D 471/08 - Bridged systems
• C07D 487/08 - Bridged systems
• C07D 213/74 - Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
• C07D 215/10 - Quaternary compounds
• C07D 217/12 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
• A61K 31/44 - Non-condensed pyridinesHydrogenated derivatives thereof
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
• A61P 3/00 - Drugs for disorders of the metabolism