333 results about "HMG-CoA reductase" patented technology

Stents with coatings comprising a combination of a restenosis inhibitor comprising an HMG-CoA reductase inhibitor and a carrier. Also provided are methods of coating stents with a combination of an HMG-CoA reductase inhibitor and a carrier. A preferred example of a restenosis inhibitor is cerivastatin. The stent coatings have been shown to release restenosis inhibitors in their active forms.

Disclosed are compounds of the formula

or a pharmaceutically acceptable salt or solvate thereof, wherein

• [0001]
  • R¹ is
  [0002]
  • R is —C(O)—N(R²⁷)(R²⁸) or

and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are pharmaceutical compositions and methods of treating cognitive or neurodegenerative diseases comprising the compounds of formula I in combination with a β-secretase inhibitor other than those of formula I, an HMG-CoA reductase inhibitor, a gamma-secretase inhibitor, a non-steroidal anti-inflammatory agent, an N-methyl-D-aspartate receptor antagonist, a cholinesterase inhibitor or an anti-amyloid antibody.

An improved technique for spinal fusion including administration of an HMG-CoA reductase inhibitor to the fusion site. The HMG-CoA reductase inhibitor is preferably delivered to the site by a carrier. More preferably, the HMG-CoA reductase inhibitor is delivered to the site by a noncompressible delivery vehicle. The invention is suitable for promoting non-anatomic or heterotopic bone growth between any bony surfaces where bone growth is desired but does not naturally occur.

A polymeric matrix for delivery of an HMG CoA reductase inhibitor such as a statin to tissue such as cardiac tissue in need thereof for the treatment or prevention of a disease or defect such as atrial fibrillation has been developed. In the preferred embodiment, a statin is delivered by means of a patch sutured to cardiac tissue at the time of cardiothoracic surgery. In the most preferred embodiment, the patch is a biodegradable material providing controlled or sustained release over a prolonged period of time, such as a week. Suitable materials include extracellular matrix, or other biodegradable hydrogels or polymeric materials providing sustained or controlled release of statin at the site of application.

The present invention relates to pharmaceutical compositions in particulate form or in solid dosage forms comprising a combination of fenofibrate and the HMG CoA reductase inhibitor rosuvastatin or a pharmaceutically active salt thereof, which upon oral administration provides a relative AUC_0-24 value (AUC_{fibric acid}/AUC_rosuvastatin) of between about 150 and about 12,000. The solid compositions are manufactured without any need of addition of water or aqueous medium and comprise at least 80% of the active substances fenofibrate and rosuvastatin in dissolved form, or, optionally, atorvastatin in micronized form, in order to ensure suitable bioavailability.

The invention discloses the nanoparticles composed of chitosan, poly-glutamic acid, and at least one bioactive agent of HMG-CoA reductase inhibitors or erythropoietin. The nanoparticles are characterized with a positive surface charge and their enhanced permeability for paracellular drug delivery.

The present invention relates to a HMG CoA Reductase inhibiting composition with improved bioavailability. The present invention also relates to a method for preparation of such composition and to the competitive inhibition of HMG CoA Reductase using such composition. The active ingredients are present in a rapidly dissolvable and more solubilized state, thereby enabling sustained and complete solubilization, more rapid dissolution upon administration to a patient, improved absorption and/or bioavailability and also increased flexibility in terms of providing the active ingredient and being capable of administration in the form of a solution, suspension, solid dispersion, solid solution or semi-solid formulation.

Disclosed are novel compounds of the formula

or a pharmaceutically acceptable salt or solvate thereof, wherein

• • R¹, R², R³, n and X are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are methods of treating a cognitive or neurodegenerative disease comprising administering to a patient I need of such treatment a combination of at least one compound of formula I and at least one compound selected from the group consisting of β-secretase inhibitors other than those of formula I, HMG-CoA reductase inhibitors, gamma-secretase inhibitors, non-steroidal anti-inflammatory agents, N-methyl-D-aspartate receptor antagonists, cholinesterase inhibitors and anti-amyloid antibodies.

This invention provides an easy and efficient process for producing a simvastatin of great use as an HMG-CoA reductase inhibitor, which comprises deacylation of lovastatin with an inorganic base and a secondary or tertiary alcohol and subjecting the resulting diol lactone to selective protection with a ketal or acetal protective group, acylation and deprotection-lactonization to give simvastatin.

A pharmaceutical composition useful as a preventive or therapeutic agent for immune-related diseases. The pharmaceutical composition includes at least HMG-COA reductase inhibitor and at least one amino alcohol compound having the following formula (I), a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof

wherein R¹ and R² each represents hydrogen; R³ represents lower alkyl or hydroxymethyl; R⁴ represents hydrogen, alkyl, alkoxy or halogen; R⁵ represents hydrogen, halogeno, cyclohexyl or phenyl; X represents vinylene (CH═CH), oxygen, sulfur or methylated nitrogen; Y represents a single bond, oxygen, sulfur or carbonyl; Z represents a single bond or C₁-C₈ alkylene; n is 2 or 3.

The present invention discusses a novel process for the synthesis of [R-(R*,R*)]-2-(4-fluorophenyl)-B,D-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid hemi calcium, atorvastatin. The compound so prepared is useful as inhibitor of the HMG-CoA reductase and may thus be used as hypolipidemic and hypocholesterolemic agent.

Pharmaceutical compositions in particulate form or in solid dosage forms comprising a combination of fenofibrate and the HMG CoA reductase inhibitor atorvastatin or a pharmaceutically active salt thereof, which upon oral administration provides a relative AUC_0-24 value (AUC_{fibric acid}/AUC_atorvastatin) of between about 250 and about 10,000. The solid compositions are manufactured without any need of addition of water or aqueous medium. Atorvastatin is optionally provided as a controlled release or a delayed release formulation resulting in a maintained LDL-lowering effect at a reduced dosage, and fenofibrate is provided in a formulation having increasing bioavailability and reduced food effect.

Disclosed herein is a lag time delayed-release combination pharmaceutical composition comprising of an angiotensin-II-receptor blocker and an HMG-CoA reductase inhibitor, as well as a preparation method thereof. The composition is designed based on chronotherapy in which active ingredients are administered to have different onset times, such that the release of each active ingredient of the composition in body can be lag time delayed to a specific rate. Also, the composition is very effective for the treatment of hypertension and the prevention of complications in patients having metabolic syndromes which show diabetes, obesity, hyperlipidemia, coronary artery diseases and the like. More specifically, the composition is a drug delivery system designed such that the release of each drug is controlled to a specific rate, and it can show the most ideal effect, when it is absorbed in body.

The instant invention provides a pharmaceutical composition comprised of a cholesterol absorption inhibitor and an HMG-CoA reductase inhibitor, one or more anti-oxidants, microcrystalline cellulose, hydroxypropyl methylcellulose, magnesium stearate and lactose. The composition need not contain ascorbic acid in order to obtain desirable stability.

A pharmaceutical composition for oral administration comprising a fixed dose combination of a first solid pharmaceutical composition containing fenofibrate as the active substance and second solid pharmaceutical composition containing an HMG-CoA reductase inhibitor such as a statin as the active substance, wherein the first and the second pharmaceutical compositions are present in separate entities in a single solid dosage form. For example a multilayer tablet, a two-layer tablet, or capsules or sachets containing the active ingredients in separate granulates or beads, either granulate or bead optionally being coated with a protective coating or an entero-coating.

Oral pharmaceutical composition containing, in the same pharmaceutical form, effective amounts of a HMG-CoA reductase inhibitor derivative and of a PPARa, especially fenofibrate. Also described is the use of some inactive ingredients which allow to improve the dissolution and/or bioavailability of the drugs from the said composition.

The combination of a HMG CoA reductase inhibitor like a statin, such as simvastatin, with a pFox inhibitor such as trimetazidine (“Simetazidine”) is particularly advantageous for treatment of end-stage complications, such as acute coronary syndrome (ACS) and chronic angina, especially in type II diabetics. The combination therapy is also useful in the treatment and/or prevention of chronic heart failure (CHF) and peripheral arterial disease (PAD). The combination of a nitric oxide (NO) mechanism with increased NO production with pFox inhibition simultaneously treats both the effect and the cause of angina. One or more oral hypoglycemic compounds (biguanides, insulin sensitizers, such as thiazolidinediones, α-glucosidase inhibitors, insulin secretagogues, and dipeptidyl peptidase IV inhibitors), protein kinase C (PKC) inhibitors, and acetyl-CoA carboxylase inhibitors can also be used in combination with the HMG CoA reductase inhibitors and/or pFox inhibitors, especially in type II diabetics, to control glucose levels and treat endothelial dysfunction. The drugs can be given in combination (e.g. a single tablet) or in separate dosage forms, administered simultaneously or sequentially. In the preferred form the statin is given in a dose of between 5 and 80 mg/day in two separate doses, and the pFox inhibitor is administered in a sustained or extended dosage formulation at a dose of 20 mg three times a day or 35 mg two times a day. The dose of the oral hypoglycemic, PKC inhibitor, or acetyl-CoA carboxylase inhibitor varies with the type of drug used.

The present invention provides methods and formulations for the treatment and prevention of cerebrovascular and cardiovascular diseases and disorders. The present invention is based, at least in part, on the discovery that administering to a subject a formulation comprising an agonist of endothelial nitric oxide synthase (eNOS), such as an HMG-CoA reductase inhibitor, and a formulation comprising a precursor of NO, such as L-arginine, may be used to treat or prevent cerebrovascular and/or cardiovascular diseases or disorders.

The present invention relates to pharmaceutical compositions comprising therapeutic combinations comprising: one or more H₃ antagonists/inverse agonists; one or more appetite suppressants selected from the group consisting of CB₁ antagonists/inverse agonists, sibutramine, phentermine and topiramate; and optionally one or more HMG-CoA reductase inhibitors. The invention also relates to medicaments and kits comprising the pharmaceutical compositions of the present invention, and methods of treating obesity, obesity related disorders and diabetes using the pharmaceutical compositions of the present invention.

Provided, among other things, is a formulation or kit comprising: (a) a pharmaceutically effective dosage of one or more a glucose-level-controlling bioactive agents selected from an α-glucodase inhibitor, sulfonylurea, meglitinide, thiazolidinediones, biguanide, insulin, dual PPARα/γ agonist, PPARγ agonist or insulin secretagogue; and (b) a pharmaceutically effective dosage of (i) one or more of an antihypertensive bioactive agent selected from an ACE inhibitor, calcium channel blocker, beta blocker, angiotension II receptor antagonist or diuretic, or (ii) one or more of an anti-dyslipidemia bioactive agent selected from a HMG-CoA reductase inhibitor, bile acid sequestrant, fibric acid derivative, sterol, cholesterol absorption inhibitor, MTP inhibitor or nicotinic acid derivative; wherein: in the case of (i) a combination of a first bioactive agent of group (a) that is metformin with a second bioactive agent of group (b), or (ii) a combination of a first bioactive agent of group (a) that is a thiazolidinedione or dual PPARα/γ agonist with an angiotension II receptor antagonist, one or more of the following applies: (I) one of the first bioactive agent or the second bioactive agent is formulated for sustained release, and the other is formulated for immediate release, each formulated for once-a-day dosing; or (II) the co-formulation or kit comprises (A) a biguanide and a thiazolidinedione and (B) one or more group (b) bioactive agents.

A composition comprises (1) a solid amorphous adsorbate comprising a cholesteryl ester transfer protein (CETP) inhibitor and a substrate; and (2) an HMG-CoA reductase inhibitor. The solid amorphous adsorbate provides concentration enhancement of the CETP inhibitor relative to a control composition consisting essentially of the unadsorbed CETP inhibitor alone, resulting in improved bioavailability.