Post by lakers on Nov 26, 2015 18:37:53 GMT -5
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Credit: peppy
Pulmonary delivery of inhibitors of phosphodiesterase type 5
US 20060099269 A1
ABSTRACT
Provided herein are compositions of 1) diketopiperazine salts of PDE5 inhibitors, and 2) DKP microparticles having a PDE5 inhibitors thereon, as well as methods for the pulmonary delivery of these compositions for the treatment of pulmonary hypertension and sexual dysfunction(s).
Publication number US20060099269 A1
Publication type Application
Application number US 11/210,709
Publication date May 11, 2006
Filing date Aug 23, 2005
Priority date Aug 23, 2004
Also published as CA2575684A1, 4 More »
Inventors Wayman Cheatham, Andrea Leone-Bay, Marshall Grant, Per Fog, David Diamond
Original Assignee Mannkind Corporation
Export Citation BiBTeX, EndNote, RefMan
[0049]
In another embodiment of the present invention a method is provided for treating sexual dysfunction comprising delivering to the pulmonary system of a patient in need of treatment for sexual dysfunction, a DKP salt of a PDE5 inhibitor or DKP microparticles comprising a PDE5 inhibitor or a salt thereof.
[0050]
To treat a patient for sexual dysfunction, the patient simply inhales the composition of the present invention before erectile function is desired at the time of a sexual encounter in a pharmacologically active amount sufficient to achieve vasodilation. Physicians and pharmacologists of ordinary skill in the art are knowledgeable in titrating doses to obtain the amount sufficient to achieve the desired clinical endpoint. A pharmacologically sufficient amount of drug is a dose that achieves the desirable clinical endpoint but does not have a undesirable side effects at a level which would result in the cessation of treatment. Typical doses for the pulmonary drug delivery of the present invention can be from about 0.1 to about 100 mg, depending on the particular drug being used. Preferably the dose delivered to the alveolar surface is in the range of from about 0.5 to about 50 mg. Although conventional oral PDE5 inhibitor formulations do not produce efficacious, systemic concentrations of the drug until several hours after administration, an oral formulation that provides a rapid onset of action is nonetheless desirable as an alternative to pulmonary delivery. A rapid-acting formulation can be prepared by use of an agent, such as a DKP, that facilitates rapid drug absorption following oral administration. Thus, an oral dosage form containing, for example, a combination of FDKP and sildenafil, either as a salt or a physical mixture, can provide a rapid onset of drug action.
[0051]
Sexual dysfunction exists in many forms and can be classified into two classes, male sexual dysfunction and female sexual dysfunction. The most common form of male sexual dysfunction is erectile dysfunction. Female sexual dysfunction can be due to a variety of causes including, but not limited to, antidepressant-induced sexual dysfunction, sexual dysfunction secondary to multiple sclerosis, anorgasmia, low arousal, delayed orgasm, decreased vaginal engorgement, dyspareunia or infertility-induced sexual dysfunction.
[0052]
In one embodiment of the present invention, a method is provided for treating pulmonary hypertension comprising delivering to the pulmonary system of a patient in need of treatment for pulmonary hypertension, a DKP salt of a PDE5 inhibitor or DKP microparticles comprising a PDE5 inhibitor or a salt thereof. For treatment of pulmonary hypertension the patient would take a dose of 0.5 to 50 mg one to six times daily. The ability to administer a therapeutically active drug directly to the internal surfaces of the lung is particularly important to the pathology of pulmonary hypertension. As compared to systemic administration, pulmonary administration can provide a significant improvement and efficiency in the treatment of this life threatening disorder.
[0053]
Pulmonary hypertension is a rare blood vessel disorder of the lung in which the pressure in the pulmonary artery (the blood vessel that leads from the heart to the lungs) rises above normal levels and may become life threatening. Symptoms of pulmonary hypertension include shortness of breath with minimal exertion, fatigue, chest pain, dizzy spells and fainting. When pulmonary hypertension occurs in the absence of a known cause, it is referred to as primary pulmonary hypertension (PPH). This term should not be construed to mean that because it has a single name it is a single disease. There are likely many unknown causes of PPH. PPH is extremely rare, occurring in about two persons per million population per year.
[0054]
Secondary pulmonary hypertension (SPH) means the cause is known. Common causes of SPH include the breathing disorders emphysema and bronchitis. Other less frequent causes are the inflammatory or collagen vascular diseases such as scleroderma, CREST syndrome or systemic lupus erythematosus (SLE). Congenital heart diseases that cause shunting of extra blood through the lungs like ventricular and atrial septal defects, chronic pulmonary thromboembolism (old blood clots in the pulmonary artery), HIV infection, liver disease and diet drugs like fenfluramine and dexfenfluramine are also causes of pulmonary hypertension.
[0055]
Many forms of pulmonary hypertension are suitable for treatment with the compositions of the present invention including, but not limited to, primary pulmonary hypertension (PPH), acute pulmonary hypertension, pulmonary arterial hypertension (PAH), pregnancy-associated hypertension such as preeclampsia, and persistent pulmonary hypertension of the newborn (PPHN).
Credit: peppy
Pulmonary delivery of inhibitors of phosphodiesterase type 5
US 20060099269 A1
ABSTRACT
Provided herein are compositions of 1) diketopiperazine salts of PDE5 inhibitors, and 2) DKP microparticles having a PDE5 inhibitors thereon, as well as methods for the pulmonary delivery of these compositions for the treatment of pulmonary hypertension and sexual dysfunction(s).
Publication number US20060099269 A1
Publication type Application
Application number US 11/210,709
Publication date May 11, 2006
Filing date Aug 23, 2005
Priority date Aug 23, 2004
Also published as CA2575684A1, 4 More »
Inventors Wayman Cheatham, Andrea Leone-Bay, Marshall Grant, Per Fog, David Diamond
Original Assignee Mannkind Corporation
Export Citation BiBTeX, EndNote, RefMan
[0049]
In another embodiment of the present invention a method is provided for treating sexual dysfunction comprising delivering to the pulmonary system of a patient in need of treatment for sexual dysfunction, a DKP salt of a PDE5 inhibitor or DKP microparticles comprising a PDE5 inhibitor or a salt thereof.
[0050]
To treat a patient for sexual dysfunction, the patient simply inhales the composition of the present invention before erectile function is desired at the time of a sexual encounter in a pharmacologically active amount sufficient to achieve vasodilation. Physicians and pharmacologists of ordinary skill in the art are knowledgeable in titrating doses to obtain the amount sufficient to achieve the desired clinical endpoint. A pharmacologically sufficient amount of drug is a dose that achieves the desirable clinical endpoint but does not have a undesirable side effects at a level which would result in the cessation of treatment. Typical doses for the pulmonary drug delivery of the present invention can be from about 0.1 to about 100 mg, depending on the particular drug being used. Preferably the dose delivered to the alveolar surface is in the range of from about 0.5 to about 50 mg. Although conventional oral PDE5 inhibitor formulations do not produce efficacious, systemic concentrations of the drug until several hours after administration, an oral formulation that provides a rapid onset of action is nonetheless desirable as an alternative to pulmonary delivery. A rapid-acting formulation can be prepared by use of an agent, such as a DKP, that facilitates rapid drug absorption following oral administration. Thus, an oral dosage form containing, for example, a combination of FDKP and sildenafil, either as a salt or a physical mixture, can provide a rapid onset of drug action.
[0051]
Sexual dysfunction exists in many forms and can be classified into two classes, male sexual dysfunction and female sexual dysfunction. The most common form of male sexual dysfunction is erectile dysfunction. Female sexual dysfunction can be due to a variety of causes including, but not limited to, antidepressant-induced sexual dysfunction, sexual dysfunction secondary to multiple sclerosis, anorgasmia, low arousal, delayed orgasm, decreased vaginal engorgement, dyspareunia or infertility-induced sexual dysfunction.
[0052]
In one embodiment of the present invention, a method is provided for treating pulmonary hypertension comprising delivering to the pulmonary system of a patient in need of treatment for pulmonary hypertension, a DKP salt of a PDE5 inhibitor or DKP microparticles comprising a PDE5 inhibitor or a salt thereof. For treatment of pulmonary hypertension the patient would take a dose of 0.5 to 50 mg one to six times daily. The ability to administer a therapeutically active drug directly to the internal surfaces of the lung is particularly important to the pathology of pulmonary hypertension. As compared to systemic administration, pulmonary administration can provide a significant improvement and efficiency in the treatment of this life threatening disorder.
[0053]
Pulmonary hypertension is a rare blood vessel disorder of the lung in which the pressure in the pulmonary artery (the blood vessel that leads from the heart to the lungs) rises above normal levels and may become life threatening. Symptoms of pulmonary hypertension include shortness of breath with minimal exertion, fatigue, chest pain, dizzy spells and fainting. When pulmonary hypertension occurs in the absence of a known cause, it is referred to as primary pulmonary hypertension (PPH). This term should not be construed to mean that because it has a single name it is a single disease. There are likely many unknown causes of PPH. PPH is extremely rare, occurring in about two persons per million population per year.
[0054]
Secondary pulmonary hypertension (SPH) means the cause is known. Common causes of SPH include the breathing disorders emphysema and bronchitis. Other less frequent causes are the inflammatory or collagen vascular diseases such as scleroderma, CREST syndrome or systemic lupus erythematosus (SLE). Congenital heart diseases that cause shunting of extra blood through the lungs like ventricular and atrial septal defects, chronic pulmonary thromboembolism (old blood clots in the pulmonary artery), HIV infection, liver disease and diet drugs like fenfluramine and dexfenfluramine are also causes of pulmonary hypertension.
[0055]
Many forms of pulmonary hypertension are suitable for treatment with the compositions of the present invention including, but not limited to, primary pulmonary hypertension (PPH), acute pulmonary hypertension, pulmonary arterial hypertension (PAH), pregnancy-associated hypertension such as preeclampsia, and persistent pulmonary hypertension of the newborn (PPHN).
