Platform drug delivery system utilizing crystal engineering and theanine dissolution

Abstract

A platform drug delivery system and a method of improving the delivery of low solubility pharmaceuticals utilizing crystal engineering and Theanine dissolution resulting in enhanced bioactivity, dissolution rate, and solid state stability.

What is claimed is: 
     
         1 . A cocrystal composition comprising:
 a quantity of a theanine enantiomer; and   a quantity of a drug from a class selected from the group consisting of nucleoside analog reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, non-purine selective xanthine oxidase inhibitors, leukotriene receptor antagonists, beta-adrenergic agonists/alpha-adrenergic agonists, antihypertensive agents, loop diuretics, thiazide diuretics, atypical antipsychotic/partial dopamine agonists, non-steroidal anti-inflammatory drugs, corticosteroids, antihistamines, antineoplastic agents, antibacterial agents, antibiotics, antiviral agents, antifungal agents, antiprotozoan agents, immediate dopamine precursor agent, catechol-o-methyltransferase inhibitors, ergoline dopamine agonists, ergot derivative/dopamine D 2 , D 3 , D 4 , 5-HT 1A , 5-HT 2A , 5-HT 2B , 5-HT 2C , α 2B  receptor agonists, antiparkinsonian agents, direct-acting skeletal muscle relaxants, noncompetitive N-methyl D-aspartate receptor antagonists, zinc salts of gluconic acid, serotonin-1b and serotonin-1d receptor agonists/antimigraine agents, cytomegalovirus nucleoside analog DNA polymerase inhibitors and guanosine analogue antiviral agents.   
     
     
         2 . The composition of  claim 1 , wherein the antihistamine is selected from the group consisting of ethanolamine and histamine H 1  receptor antagonists. 
     
     
         3 . The composition of  claim 1 , wherein the antineoplastic agent is selected from the group consisting of protein tyrosine kinase inhibitors, antileukemic drugs, topoisomerase 1 inhibitors, and anthracycline topoisomerase inhibitors. 
     
     
         4 . The composition of  claim 1 , wherein the antibiotics are selected from the group consisting of cephalosporins, aminopenicillins, macrolides, sulfonamides, nitroimidazole antibiotics, fluorinated bistriazole antibiotics, and cyclic lipopeptide antibiotics. 
     
     
         5 . The composition of  claim 1 , wherein the direct-acting skeletal muscle relaxant is a hydantoin derivative. 
     
     
         6 . The composition of  claim 1 , wherein theanine enantiomer is selected from the group consisting of an L-enantiomer of the alpha variant of theanine, a D-enantiomer of the alpha variant of theanine, a DL-enantiomer of the alpha variant of theanine, an L-isomer of the alpha variant of theanine, a D-isomer of the alpha variant of theanine, a DL-racemic mixture of the alpha variant of theanine, an S-isomer of the alpha variant of theanine, an R-isomer of the alpha variant of theanine, an S,R-racemic mixture of the alpha variant of theanine, rotamers of the alpha variant of theanine, tautomers of the alpha variant of theanine, salt forms of the alpha variant of theanine, hydrates of the alpha variant of theanine, an L-enantiomer of the beta variant of theanine, a D-enantiomer of the beta variant of theanine, a DL-enantiomer of the beta variant of theanine, an L-isomer of the beta variant of theanine, a D-isomer of the beta variant of theanine, a DL-racemic mixture of the beta variant of theanine, an S-isomer of the beta variant of theanine, an R-isomer of the beta variant of theanine, an S,R-racemic mixture of the beta variant of theanine, rotamers of the beta variant of theanine, tautomers of the beta variant of theanine, salt forms of the beta variant of theanine, and hydrates of the beta variant of theanine. 
     
     
         7 . The composition of  claim 1 , wherein the theanine enantiomer is selected from the group consisting of L-theanine, D-theanine, and DL-theanine. 
     
     
         8 . A cocrystal composition comprising:
 a quantity of a theanine enantiomer; and   a quantity of a drug selected from the group consisting of lasix, aspirin, epinephrine, zinc gluconate, dantrolene sodium, levodopa, entacapone, bromocriptine, cabergoline, nilotinib, memantine, ibuprofen, efavirenz, zidovudine, metronidazole, valganciclovir, fluconazole, ampicillin, erythromycin, sulfamethoxzole, cefdinir, cefadroxil, amoxicillin, daptomycin, acyclovir, febuxostat, hydrochlorothiazide, sumatriptan, prednisone, zinc gluconate, doxorubicin, irinotecan, aripiprazole, diflunisal, zafirulkast, and fexofenadine.   
     
     
         9 . A cocrystal composition comprising:
 a quantity of a theanine enantiomer; and   a quantity of a drug for treating a condition selected from the group consisting of acute pulmonary edema/congestive heart failure; acute myocardial infarction; acute ischemic stroke; acute allergic reactions, anaphylactic reactions from medication, food, latex, insect bites/stings, cardiac arrest, acute exacerbation of asthma, ventricular fibrillation, airway obstruction; Australian box jelly fish envenomations; neurologic emergencies; diseases/conditions associated with excessive amounts of glutamate; Parkinson's disease; hyperprolactinemia including amenorrhea with or without galactorrhea, infertility or hypogonadism, prolactin-secreting adenomas, acromegaly, post encephalitic Parkinson's disease; hyperprolactinemic disorders, either idiopathic or due to pituitary adenomas; Imatinib resistant chronic myelogenous leukemia, Alzheimer's disease, Huntington's disease, dementia, amyotrophic lateral sclerosis; neurodegenerative diseases/conditions; acute renal colic; acute pericarditis; ligament injury; HIV/AIDS; clostridium difficile, trichomoniasis, bacterial infections of the vagina, acne rosacea, giardiasis, amoebiasis, abscess, surgical wound infections, helicobacter infections, pseudomembranous enterocolitis, bacteroides infections; cytomegalovirus retinitis in AIDS patients, AIDS associated opportunistic infections, CMV disease in patients who have received an organ transplant; herpes simplex encephalitis, herpes labialis, genital herpes, varicella-zoster, acute mucocutaneous HSV infections in immunocompromised patients, acute chickenpox in immunocompromised patients, ophthalmic herpes, herpes simplex blepharitis; oral candida/fungal infection; listeriosis; bronchitis, diphtheria, legionnaires disease, pertussis pneumonia, dental prophylaxis; uncomplicated urinary tract infections, pneumocystis carinii pneumonia, toxoplasmosis, shigellosis, traveler's diarrhea; community-acquired pneumonia, acute exacerbations of chronic bronchitis, acute maxillary sinusitis, pharyngitis, tonsillitis, uncomplicated skin and soft tissue infections, acute bacterial otitis media; impetigo/soft tissue infections; pharyngitis, tonsillitis, uncomplicated skin infections, uncomplicated soft tissue infections, lower respiratory infections, early stage Lyme disease;  staphylococcus aureus  bacteremia including right sided endocarditis, complicated skin and skin structure gram-positive bacterial infections including MRSA; gout/hyperuricemia; heart failure, hypertension, pulmonary edema, fluid retention associate with ascites, liver cirrhosis, nephrotic syndrome; hypertension, heart failure, diabetes insipidus, fluid retention in patients with congestive heart failure, cirrhosis of the liver, nephrotic syndrome in patients taking steroids, nephrotic syndrome in patients taking estrogen; migraine, cluster headaches; Ramsay Hunt Syndrome; inflammation, autoimmune disease, Bell's palsy, Hashimoto's encephalopathy, skin disease, mild to moderate allergies, asthma, COPD, chronic inflammatory demyelinating polyneuropathy, rheumatic disorders, allergic reactions, ulcerative colitis, Crohn's disease, adrenocortical insufficiency, thyroiditis, laryngitis, sinusitis, mild to moderate urticaria, recurrent pericarditis, multiple sclerosis, nephrotic syndrome, myasthenia gravis, poison oak exposure, acute lymphoblastic leukemia, Non-Hodgkin lymphoma, hodgkin's lymphoma, multiple myeloma and other hormone-sensitive tumors, uveitis, sarcoidosis; rhinovirus colds; acute lymphoblastic leukemia, acute myelobastic leukemia, Wilm's tumor, neuroblastoma, soft tissue and bone sarcomas, ovarian carcinoma, transitional cell bladder carcinoma, thyroid carcinoma, gastric carcinoma, Hodgkin's disease, malignant lymphoma, small cell histologic type bronchogenic carcinoma, axillary lymph node involvement following resection of primary breast cancer; metastatic carcinoma of the colon and rectum; dopamine-responsive dystonias; schizophrenia, bipolar disorder, autism; pain; asthma; hay fever; and stabilization of bimembrane structures.   
     
     
         10 . The composition of  claim 7 , wherein the theanine enantiomer is selected from the group consisting of an alpha variant of theanine and a beta variant of theanine. 
     
     
         11 . The composition of  claim 10 , wherein the alpha variant of theanine is selected from the group consisting of L-homotheanine, D-homotheanine, DL-homotheanine, L-bishomotheanine, D-bishomotheanine, and DL-bishomotheanine. 
     
     
         12 . The composition of  claim 10 , wherein the alpha variant of theanine is a homologous analog of theanine. 
     
     
         13 . The composition of  claim 10 , wherein the alpha variant of theanine contains a functional group selected from the group consisting of linear, cyclic, or branched alkyl and derivatives thereof; linear, cyclic, or branched alkenyl and derivatives thereof; and
 aromatic radicals and derivatives thereof.   
     
     
         14 . The composition of  claim 13 , wherein the aromatic radicals are aryl radicals. 
     
     
         15 . The composition of  claim 7 , wherein the theanine enantiomer is a racemic mixture of a beta variant of theanine containing a functional group selected from the group consisting of linear, cyclic, or branched alkyl groups and derivatives thereof; linear, cyclic, or branched alkenyl groups and derivatives thereof; and aromatic radicals and derivatives thereof. 
     
     
         16 . The composition of  claim 15 , wherein the aromatic radicals are aryl radicals. 
     
     
         17 . The composition of  claim 7 , wherein the theanine enantiomer is an S enantiomer of a beta variant of theanine containing a functional group selected from the group consisting of linear, cyclic, or branched alkyl groups and derivatives thereof; linear, cyclic, or branched alkenyl groups and derivatives thereof; and aromatic radicals and derivatives thereof. 
     
     
         18 . The composition of  claim 17 , wherein the aromatic radicals are aryl radicals. 
     
     
         19 . The composition of  claim 7 , wherein the theanine enantiomer is an R enantiomer of a beta variant of theanine containing a functional group selected from the group consisting of linear, cyclic, or branched alkyl groups and derivatives thereof; linear, cyclic, or branched alkenyl groups and derivatives thereof; and aromatic radicals and derivatives thereof. 
     
     
         20 . The composition of  claim 19  wherein the aromatic radicals are aryl radicals. 
     
     
         21 . The composition of  claim 15 , wherein the mixture further comprises a sugar alcohol. 
     
     
         22 . The composition of  claim 21 , wherein the sugar alcohol has a configuration selected from the group consisting of the L-configuration and the D-configuration. 
     
     
         23 . The composition according to  claim 9 , wherein the neurologic emergency is selected from the group consisting of malignant hyperthermia, 3,4 methylenedioxymethamphetamine intoxication, serotonin syndrome, 2,4-dinitrophenol poisoning. 
     
     
         24 . The composition according to  claim 9 , wherein the diseases/conditions associated with excessive amounts of glutamate is selected from the group consisting of spinal cord injury, stroke, traumatic brain injury, multiple sclerosis. Alzheimer's disease, Parkinson's disease, alcoholism, alcohol withdrawal, over-rapid benzodiazepine withdrawal, Huntington's disease, hypoglycemia, damage to a newborns brain caused by interrupted oxygen supply during delivery, exposure to nerve gas; and chronic nerve damage. 
     
     
         25 . The composition according to  claim 24 , wherein the chronic nerve damage is from a condition selected from the group consisting of in such conditions as glaucoma, amyotrophic lateral sclerosis, and HIV dementia. 
     
     
         26 . The composition according to  claim 9 , wherein the Parkinson's disease is selected from the group consisting of idiopathic Parkinson's disease and postencephalitic Parkinson's disease. 
     
     
         27 . The composition according to  claim 9 , wherein the neurodegenerative diseases/conditions is selected from the group consisting of multiple sclerosis, cerebral palsy, spinal cord injury, and cerebrovascular accident. 
     
     
         28 . The composition according to  claim 9 , wherein the pain is dental pain, migraine pain, cluster headache pain, soft tissue injury pain, inflammatory pain, renal colic pain, or marine envenomation pain. 
     
     
         29 . The composition according to  claim 9 , wherein the skin structure gram-positive bacterial infections includes MRSA. 
     
     
         30 . A cocrystal composition comprising:
 a quantity of L-theanine; and a quantity of a chemical composition selected from the group consisting of acyclovir, amoxicillin, ampicillin, aripiprazole, bromocriptine, cabergoline, cefadroxil, cefdinir, dantrolene, daptomycin, diflunisal, doxorubicin, efavirenz, entacapone, epinephrine, erythromycin, febuxostat, fexofenadine, fluconazole, furosemide, hydrochlorothiazide, (R)-ibuprofen, irinotecan, levodopa, memantine, metronidazole, nilotinib, prednisone, sulfamethoxazole, sumatriptan, valganciclovir, zafirlukast, zidovudine, and gluconate-zinc.   
     
     
         31 . A method of improving a physical property of an active pharmaceutical ingredient, comprising the step of combining the active pharmaceutical ingredient with a quantity of L-theanine, wherein the physical property is selected from the group consisting of solubility, stability, and dissolution rate.