USOO702636OB1

(12) United States Patent (10) Patent No.: US 7,026,360 B1 Fest0 (45) Date of Patent: Apr. 11, 2006

(54) PHARMACEUTICAL COMPOSITIONS FOREIGN PATENT DOCUMENTS CONTAINING COMPOUNDS WITH EP O 390 206 10, 1990 ACTIVITY FOR THE ENHANCEMENT OF EP O390206 * 10, 1990 ABSORPTION OF ACTIVE INGREDIENTS EP 0 723 775 T 1996 JP 62-42922 2, 1987 (75) Inventor: Norberto Festo, Lugano (CH) OTHER PUBLICATIONS (73) Assignee: Inpharma S.A., Lugano (CH) Corti, P., et al., “Near infrared reflectance spectroscopy in the study of atopy Part 3. Interactions between the skin and (*) Notice: Subject to any disclaimer, the term of this fomblins.” ANALYST, vol. 123, pp. 2313-2317, 1998. patent is extended or adjusted under 35 Bonina, F., et al., “Three phase emulations for controlled U.S.C. 154(b) by 0 days. delivery in the cosmetic field.” Int. J. Cosmetic Sci, Vol. 14, (21) Appl. No.: 09/673,411 pp. 65-74, 1992. Lehmler, Hans-Joachim, et al., “Liquid Ventilation—A New (22) PCT Filed: Feb. 16, 2000 Way to Deliver Drugs to Diseased Lungs?.” Chemtech, vol. 29, No. 10, 7-12, pp. 1-10 (Oct. 1999). (86). PCT No.: PCT/BOO/OO167 * cited by examiner S 371 (c)(1), Primary Examiner Cecilia J. Tsang (2), (4) Date: Oct. 17, 2000 Assistant Examiner Taylor Victor Oh (74) Attorney, Agent, or Firm—Ladas & Parry LLP (87) PCT Pub. No.: WO00/48636 (57) ABSTRACT PCT Pub. Date: Aug. 24, 2000 The new pharmaceutical compositions contain, apart from (30) Foreign Application Priority Data one or more active ingredient(s), between 0.01 and 60% w/w Feb. 18, 1999 (CH) ...... O311/99 of the compounds of formula I (51) Int. Cl. A6 IK3I/02 (2006.01) (52) U.S. Cl...... 514/759 (58) Field of Classification Search ...... 568/600, CF 568/615,677,683, 679; 514/759 See application file for complete search history. with n and mid 18 and <46 and with molecular weights between -600 and ~8000 for the enhancement of absorption (56) References Cited of the active ingredient(s). Moreover, such compositions U.S. PATENT DOCUMENTS may contain also between 0.01 and 20% w/w of Phosphati dylcholine. 5,304,334 A 4, 1994 Lahanas et al. 5,376,359 A 12/1994 Johnson 5,686,102 A * 11/1997 Gross et al...... 424/450 29 Claims, No Drawings US 7,026,360 B1 1. 2 PHARMACEUTICAL COMPOSITIONS Surprisingly, it was found that inclusion of a quantity of CONTAINING COMPOUNDS WITH PFPE at concentrations between 0.01% w/w and 60% w/w, ACTIVITY FOR THE ENHANCEMENT OF in topical and/or transdermal (drug delivery systems) for ABSORPTION OF ACTIVE INGREDIENTS mulations, increases the percutaneous absorption of active ingredients by over 5–20 times their normal value, thus The invention described herein refers to pharmaceutical enabling improved absorption and optimization of their compositions, to the use of compounds as agents with systemic effects through Suitable pharmaceutical presenta activity for the enhancement of absorption of active ingre tions. dients and to specific compounds. The problems related to percutaneous absorption of active 10 DETAILED DESCRIPTION OF THE ingredients in topical and transdermal pharmaceutical pre INVENTION sentations (drug delivery systems) is known and has been the subject matter of patents 1 Peroutaneous absorption: Comprehension of the invention is facilitated by the mechanisms-methodology-drug delivery, 2 Ed., Bronaugh description of a number of assessments on the percutaneous Maibach, MARCEL DEKKER INC. 15 absorption of certain formulations containing different Among the most significant examples reported In Scien active ingredients. tific literature it is possible to mention the enhancing activity Example A illustrates the increase in permeability by of decylmethylsulfoxide in increasing percutaneous absorp approx. 10 times of a formulation containing Troxerutine tion of idoxuridine 2 Touitou. E. (1988). Int. J. Pharm. and 3% PFPE as compared with that of a reference formu 43:1. The effect of dodecylazacycloheptan-2-one (Lauroca- 20 lation. pram, AZone) in enhancing absorption of various molecules Example B demonstrates the correlation between PFPE was Investigated by Stoughton 3 Stoughton, R. B. (1982), concentration and percutaneous absorption of formulations Arch. Dermatol. 118: 474 and by Sugibayashi 4 Sugiba containing NimeSulide and increasing concentrations of yashi, K., Hosoya, K. Morimoto, Y., and Higuchi, W. 1. PFPE. (1985), J. Pharm. Pharmacol. 37: 578. 25 Substances made available on the market and initially Example C contains a comparison of the permeation used in fields other than the pharmaceutical sector, Subse speed of formulations containing non-steroidal antiinflam quently proved to be of remarkable importance also for the matory drugs versus formulations to which 3% PFPE has pharmaceutical industry. Among these, we can find the been added. Perfluoropolyether class of compounds (PFPE) 5 obtained 30 by polymerization of hexafluoropropene with oxygen acti Example A vated by UV radiation and subsequent treatment to obtain a cosmetic product 6 as an excipient for preparations used in Verification of the percutaneous absorption of TROX the manufacture of products with a barrier effect 7. ERUTINE through pig skin using various formulations 35 containing different types of absorption enhancers. In par SUMMARY OF THE INVENTION ticular, this involved investigation of the release of TROX ERUTINE from formulations containing PFPE, Nor-cheno The following invention consists in the use of PFPE to deoxycolic acid and transcutol, Versus a reference enhance absorption of pharmacologically active ingredients formulation. in topical pharmaceutical presentations and/or in transder- a mal formulations (drug delivery systems) containing mix Experimental Section: tures of at least one active ingredient for the enhancement of Apparatus: Franz Cells (manufacturer: Crown Glass Com absorption. pany Inc., New Jersey) These compounds, if included in pharmaceutical presen tations containing an association or at least one active as Franz diffusion cells are one of the main systems used for ingredient, can modify the permeating capacity of the active the investigation of ex-vivo permeation. This study involved ingredients through the skin, demonstrating a Surprising and the use of three cells each with a 9 mm diameter donor unexpected capacity to promote the penetration of the active compartment corresponding with a diffusion area of 64 ingredient. mm. In accordance with the first aspect of the invention, The receptor compartment has a capacity of 4.8 ml. The inclusion of a quantity of PFPE may be applied in traditional 50 receptor chamber is heated to 37° C. 1. topical formulations such as, for example, but not limited to: Test system: HPLC, Gilson, Mod. 305 with Spectra Physics creams, liquid emulsions, ointments, lotions, microemul detector, Spectra 200 Mod. sions, foams, gels, aspersion powders; and in transdermal Formulations: formulations (drug delivery systems). 55 The term PFPE means molecules with a chemical struc ture

A. B C D

Troxerutine 3 3 3 3 Phosphatidylcholine 7 7 7 7 CF Tocopherol acetate O.S O.S O.S O.S Sepigel 305 4 4 4 4 Methyl-p-hydroxybenzoate O.15 O.15 O.15 O.15 where n/m=20=40 Propyl-p-hydroxybenzoate O.OS O.OS O.OS O.OS Phenoxyethanol 1 1 1 1 with molecular weights between 650 and 6250, C.A.S. 65 PFPE 3 name: 1-Propene, 1,1,2,3,3,3-hexafluoro-, oxidized and Nor-chenodeoxycolic acid 0.4 polymerized C.A.S. number: 69991-67-9. US 7,026,360 B1 4 various formulations containing different concentrations of -continued PFPE versus a reference formulation. A. B C D Formulations: Transcutol 15 Purified water q.S. to: 100 1OO 100 100 A. B C D Preparation of the Skin Nimesulide 5 5 5 5 The pig skin samples were taken from the internal ear of 10 Lactic acid 2 2 2 2 Ethyl alcohol 95° 4 4 4 4 pigs that had just been sacrificed. Glycerine 5 5 5 5 The samples were soaked in buffer solution at pH 7.4 for PFPE 1.5 3 4.5 24 hours at 4° C. Sepigel 305 4 4 4 4 The sections of connective tissue and muscle were Sub Phosphatidylcholine 2 2 2 2 Methyl-p-hydroxybenzoate O.15 O.15 O.15 O.15 sequently removed from the skin and the sample was cut into 15 Propyl-p-hydroxybenzoate O.OS O.OS O.OS O.OS 2x2 cm Squares. Purified water q.S. to: 100% 100% 100% 100% The skin samples were stored at -20° C. HPLC Operating Test Conditions Results The results on permeability are summarized in the fol Column: KP 18, 5 micron Licrospher 100 lowing table Mobile phase: 20% acetonitrile 80% phosphate buffer at pH 6.6 Flow: 1 ml/min Pressure: 1.52 Kipsi Wavelength: 245 nm. 25 neg of permeated Ninesulide RT: 8.51 TIME (h) A. B C D O.S O.15 O16 O.S9 O.83 Procedure 1 0.27 O.39 O.S9 1.21 The pig skin is placed between the donor compartment 30 2 O.35 0.72 0.97 1.70 and the receptor chamber with the external skin surface 4 O.86 1.14 1.24 1.91 facing the upper compartment. The test formulation is 6 1.15 1.54 2.21 2.38 placed inside the donor compartment. 8 1.54 2.24 3.21 3.73 The receptor chamber is filled with a phosphate buffer 24 3.53 6.OO 9.71 9.86 solution at pH 7.4 and at intervals between 0.5 and 8 hours, 35 2 ml of solution are drawn from this chamber. When each sample is taken fresh buffer solution heated to 37° C. is Conclusions added in order to replenish the initial volume. The samples are then tested using a HPLC method. Each test is repeated Formulations B, C, D demonstrated an increasing capac three times. 40 ity to permeate the skin; this permeating capacity is corre Results lated with the increasing percentage content of PFPE. The results on percutaneous absorption are Summarized in the table below Example C 45 Verification of absorption after 8 hours, oftopical formu lations containing antiinflammatory drugs versus formula neg of permeated Troxerutine tions which also contain 3% PFPE, through pig skin, using TIME (h) A. B C D Franz cells, as described in Example A. O.S 18.89 13.26 8.29 13.7 50 1 77.48 43.04 17.17 50.51 2 345.29 102.6 S8.19 232.84 4 1,289.11 390.80 229.46 636.68 mcg of permeated active ingredient after 6 3,999.07 614.95 530 1,053.09 Active ingredient 8 hours 8 12,042 1,090 714.6 1434.90 55 contained in the Base formula + 3% topical formulation Base formula PFPE Conclusions Ketoprofen O.64 5.33 Formulations B, C, D did not show any difference in Diclofenac Sodium 1.82 8.66 Ibuprofen O.21 6.84 absorption, whilst at the eighth hour, formulation A contain Etodolic Acid O.S3 9.93 ing PFPE, demonstrated a degree of absorption that was 60 Piroxicam 1.19 7.94 about 9–10 times greater than that of reference formulation D. The invention is characterized by the claims at the end of Example B this description. According to the invention the pharmaceu 65 tical compositions contain, apart from one or more active Verification of the absorption of NIMESULIDE through ingredient(s), between 0.01 and 60% w/w of the compounds pig skin, using Franz cells, as described in Example A, using of formula I US 7,026,360 B1 6 2) B-Adrenergic agonists such as Albuterol, Bambuterol, Bitolterol, Carbuterol, Clenbuterol, Clorprenaline, Deno pamine, Dioxethedrine, Dopexamine, Ephedrine, Epi nephrine, Etafedrine, Ethylnorepinephrine, Fenoterol, CF Formoterol, Hexoprenaline, Ibopamine, Isoetharine, Iso proterenol, Mabuterol, Metaproterenol, Methoxyphe namine, Oxyfedrine, Pirbuterol, Prenalterol, Procaterol, with n and mid 18 and <46 and with molecular weights Protokylol, Reproterol, Rimiterol, Ritodrine, Soterenol, between ~600 and ~8000, as compounds with activity for Terbuterol and Xamoterol. the enhancement of active ingredient absorption. 10 3) O-Adrenergic blockers such as Amosulalol, Arotinolol. Such pharmaceutical compositions may also contain Dapiprazole, Doxazosin, Ergoloid, Mesylates Fenspiride, between 0.01 and 20% w/w of Phosphatidylcholine, the Indoramin, Labetalol, Nicergoline, PraZosin, Terazosin, compositions preferred are those with 0.1 to 30% w/w of the Tolazoline, Trimazosin and Yohimbine. compounds of formula I with n and mid-24 and <36 and with 4) B-Adrenergic blockers such as Acebutolol, Alprenolol. molecular weights between 1000 and 4000 and with 0.1 to 15 Amosulalol, Arotinolol, Atenolol, Befunolol, Betaxolol, 10% w/w of Phosphatidylcholine. Bevantolol, Bisoprolol, Bopindolol, Bucumolol, Bufe tolol, Bufuralol, Bunitrolol, Bupranolol, Butidrine, They may also contain other compatible ingredients that Hydrochloride, Butofilolol, Carazolo, Carteolol are present in the form of creams, emulsions, ointments, Carvedilol, Celiprolol, Cetamolol, Cloranolol, Dilevalol, lotions, foams, gels and transdermal formulations. Epanolol, Esmolol, Indenolol Labetalol, Levobunolol, The invention also includes the use of the compounds of Mepindolol, Metipranolol, Metoprolol, Moprolol Nadox formula I olol, Nifenalol, Nipradillol, Oxprenolol, Penbutolol, Pin dolol, Practolol, Pronethalol, Propranolol, Sotalol, Sulfi malol, Talinolol, Tertatolol, Timolol, Toliprolol and 25 Xibenolol. 5) Alcohol deterrents such as Calcium Cyanamide Citrated, CF Disulfiram, Nadide and Nitrefazole 6) Aldose reductase inhibitors such as Epalrestat, Ponalr estat, Sorbinil and Tolrestat. with n and mid 18 and <46, preferably >24 and <36, and with 30 7) Anabolics Such as Androisoxazole, Androstenediol. molecular weights between -600 and ~8000, preferably Bolandiol, Bolasterone, Clostebol, Ethylestrenol, Formyl between 1000 and 4000, in pharmaceutical compositions for dienolone, 4-Hydroxy-19-nortestosterone, Methandriol, topical external or internal use for the enhancement of Methenolone Methyltrienolone Nandrolone Nandrolone absorption of active ingredients through the derma, cutis, Decanoate, Nandrolone p-Hexyloxyphenylpropionate, mucosa, rectum, vagina and urethra, with or without Phos 35 Nandrolone Phenpropionate, Norbolethone, Oxymester phatidylcholine. In particular, such use regards active ingre one Pizotyline, Quinbolone, Stenbolone and Trenbolone. dients that have anabolic, analgesic, androgenic, anesthetic, 8) Analgesics (dental) such as Chlorobutanol, Clove and anorectic, anthelmintic, antiallergic, antiamebic, antiandro Eugenol. genic, antianginal, antiarrhythmic, antiarteriosclerotic, anti 9) Analgesics (narcotic) Such as Alfentanil, Allylprodine, arthritic and antirheumatic, antibacterial, anticholinergic, 40 Alphaprodine, Anileridine, Benzylmorphine, Bezitra anticonvulsant, antidepressant, antidiabetic, antidiarrheal, mide, Buprenorphine, Butorphanol, ClonitaZene, antidiuretic, antiestrogenic, antibiotic, antiglaucoma, anti Codeine, Codeine Methyl Bromide, Codeine Phosphate, gonatropic, antihistaminic, antihyperlipoproteinemic, anti Codeine Sulfate, Desomorphine, Dextromoramide, Dezo hyperthyroid, antihypertensive, anti-inflammatory, antima cine, Diampromide, Dihydrocodeine, Dihydrocodeinone, larial, antimigraine, antinauseant, antineoplastic, 45 Enol Acetate, Dihydromorphine, Dimenoxadol Dime antiparkinsonian, antiprotozoal, antipruritic, antipsoriatic, pheptanol, Dimethylthiambutene, Dioxaphetyl Butyrate, antipsychotic, antipyretic, antiseptic, antispasmodic, anti Dipipanone Eptazocine Ethoheptazine Ethylmethylthiam thrombotic, antitussive, antiulcer, antiviral, anxiolytic, bron butene, Ethylmorphine, Etonitazene, Fentanyl, Hydroc chodilator, CA-blocking or regulating, cardiotonic, stimu odone, Hydromorphone, Hydroxypethidine) Isometha lating, decongestant, diuretic or enzymatic effect. More 50 done, Ketobemidone, Levorphanol, Lofentanil, specifically, use of this invention regards Troxerutine and Meperidine, Meptazinol, Metazocine, Methadone Hydro Nimesulide and, also chloride, Metopon Morphine, Morphine Derivatives, 1) O-Adrenergic agonists such as Adrafinil, Adrenoloneu, Myrophine, Nalbuphine, Narceline, Nicomorphine Nor Amidephrine, Apraclonidine, Budralazine, Clonidine, levorphanol, Normethadone, Normorphine, Norpipanone, Cyclopentamine, Detomidine, Dimetofrine, Dipivefrin, 55 Opium, Oxycodone, Oxymorphone, Papaveretum, Penta Ephedrine, Epinephrine, Fenoxazoline, Guanabenz, Zocine, Phenadoxone, Phenazocine, Phenoperidine, Pimi Guanfacine, Hydroxyamphetamine, Ibopamine, Indiana nodine Piritramide, Proheptazine, Promedol, Properidine, Zoline, Isometheptene, Mephentermine, Metaraminol, Propiram, Propoxyphene, Sufentanil and Tilidine. Methoxamine Hydrochloride, Methylhexaneamine, Meti 10) Analgesics (non-narcotic) Such as Acetaminophen, Zolene, Midodrine, Naphazoline, Norepinephrine, Nor 60 Acetaminosalol, Acetanilide, Acetylsalicylsalicylic Acid, fenefrine, Octodrine, Octopamine, Oxymetazoline, Phe Alclofenac, Aminoprofen, Aloxiprin, Aluminum, Bis nylephrine Hydrochloride, Phenylpropanolamine (acetylsalicylate), Aminochlorthenoxazin, 2-Amino-4-pi Hydrochloride, Phenylpropylmethylamine, Pholedrine, coline, Aminopropylon, Arminopyrine, Ammonium Sali Propylhexedrine, Pseudoephedrine, Rilmenidine, Syn cylate, Antipyrine, Antipyrine, Salicylate, Antrafenine, ephrine, Tetrahydrozoline, Tiamenidine, Tramazoline, 65 ApaZone, Aspirin, Benorylate, Benoxaprofen, BenZpip Tuaminoheptane, TymaZoline, Tyramine and Xylometa erylon, BenZydamine, p-Bromoacetanilide, 5-Bromosali Zoline. cylic Acid Acetate, Bucetin, BufeXamac, Bumadizon, US 7,026,360 B1 7 8 Butacetin, Calcium Acetylsalicylate, Carbamazepine, amine Sulfates, Diethylpropion, Diphemethoxidine, Carbetidine, Carbiphene, Carsalam, Chloralantipyrine N-Ethylamphetamine, Fenbutrazate, Fenfluramine, Fen Chlorthenoxazin(e), Choline Salicylate, Cinchophen, proporex, Furfurylmethylamphetamine, Levophacetoper Ciramadol, Clometacin, Cropropamide, Crotethamide, ate, Mazindol, Mefenorex, Metamfepramone, Metham Dexoxadrol, Difenamizole. Diflunisal, Dihydroxyalumi phetamine, Norpseudoephedrine, Phendimetrazine, num, Acetylsalicylate, Dipyrocetyl. Dipyrone, Emorfa Phenmetrazine, Phenpentermine, Phenylpropanolamine Zone, Enfenamic, Acid, Epirizole, Etersalate, Ethenza Hydrochloride and Picilorex. mide, Ethoxazene, Etodolaci, Felbinac, Fenoprofen, 14) Anthelmintics (Cestodes) Such as Arecoline, Aspidin, Floctafenine, Flufenamic, Acid, Fluoresone, Flupirtine, Aspidinol, Dichlorophen(e), Embelin, Kosin, Napthalene, FluproduaZone, Flurbiprofen, Fosfosal, Gentisic Acid, 10 Niclosamide, Pellertierine, Pellertierine Tannate and Glafenine, ibufenac, Imidazole, Salicylate, Indomethacin, Quinacrine. Indoprofen, IsofeZolac, Isoladol, Isonixin, Ketoprofen, 15) Anthelmintics (Nematodes) such as Alantolactone, Ketorolac, p-Lactophenetide, Lefetamine, Loxoprofen, Amoscanate, Ascaridole, Bephenium, Bitoscanate, Car Lysine Acetylsalicylate, Magnesium Acetylsalicylate, bon Tetrachloride, Carvacrol, Cyclobendazole, Diethyl Methotrimeprazine, Metofoline, Miroprofen, Morazone, 15 carbamazine, Diphenane, Dithiazanine Iodide, Dyman Morpholine Salicylate, Naproxen, Nefopam, NifenaZone, thine, Gentian Violet, 4-Hexylresorcinol, Kainic Acid, 5"Nitro-2'propoxyacetanilide, Parsalmide, Perisoxal, Mebendazole, 2-Napthol, Oxantel, Papain, Piperazine, Phenacetin, Phenazopyridine, Hydrochloride, Phenocoll, piperazine Adipate, Piperazine Citrate, Piperazine Edetate Phenopyrazone, Phenyl Acetylsalicylate, Phenyl Salicy Calcium, Piperazine Tartrate, Pyrantel, Pyrvinium Pamo late, Phenyramidol, Pipebuzone, Piperylone, Prodilidine, ate, C.-Santonin, Stilbazium Iodide, Tetrachloroethylene, Propacetamol Propyphenazone, Proxazole, Quinine Sali Tetramisole. Thiabendazole, Thymol Thymyl N-Isoamyl cylate, Ramifenazone, Rimazolium Metilsulfate, Salac carbamate, Triclofenol Piperazine and Urea Stibamine. etamide, Salicin, Salicylamide, Salicylamide O-Acetic 16) Anthelmintics (Onchocerca) such as Ivermectin and Acid, Salicylsulfuric Acid, Salsalate Salverine, Simetride, Suramin Sodium. Sodium Salicylate, Sulfamipyrine, Suprofen, Talniflu 25 17) Anthelmintics (Schistosoma) Such as Amoscanate, mate, Tenoxicam, Terofenamate, Tetradrine, Tinoridine, Amphotalide, Antimony Potassium Tartrate, Antimony Tolfenamic Acid, Tolpronine, Tramadol, Viminol, Xen Sodium Gluconate, Antimony Sodium Tartrate, Antimony bucin and Zomepirac. Sodium Thioglycollate, Antimony Thioglycollamide, 11) Androgens such as Boldenone, Fluoxymesterone, Becanthone, Hycanthone, Lucanthone Hydrochloride, Mestanolone Mesterolone, Methandrostenolone, 17-Me 30 Niridazole, Oxamniquine, Praziguantel, StibocaPtate, Sti thyltestosterone, Methaltestosterone, 17O-Methyltest bophen and Urea Stibamine. osterone 3-Cyclopentyl Enol Ether, Norethandrolone, 18) Anthelmintics (Trematodes) such as Anthiolimine and Normethandrone, Oxandrolone, Oxymesterone, Tetrachloroethylene. Oxymetholone, Prasterone, Stanolone, Stanozolol, Test 19) Antiacne drugs such as Algestone Acetophenide, AZelaic osterone, Testosterone 17-Chloral Hemiacetal, Testoster 35 Acid, Benzoyl Peroxide, Cyoctol, Cyroterone, Motretin one 17 B-Cypionate, Testosterone Enanthate, Testosterone ide, Resorcinol, Retinoic Acid and Tetroquinone. Nicotinate, Testosterone Phenyl Acetate, Testosterone 20) Antiallergics such as Amlexanox, Astemizole, AZelas Propionate and Tiomesterone. tine, Cromolyn, Fenpiprane. Histamine, Ibudilast, 12) Anesthetics (intravenous) such as Acetamidoeugenol, Nedocromil, Oxatomide, Pentigetide, Poison Ivy Extract, Alfadolone Acetate, Alfaxalone, Ambucaine. Amolanone, 40 Poison Oak Extract, Poison Sumac Extract, Repirinast, Amylocaine, Hydrochloride, Benoximate, Betoxycaine, Tranilast, Traxanox and Urushiol. Biphenamine, Bupivacaine. Butacaine. Butamben, Buta 21) Antiamebics Such as Arsthinol, Bialamicol, CarbarSone, nilicaine. Butethamine. Buthalital Sodium, Butoxycaine, Cephaeline, Chlorbetamide, Chilorquine, Chlorphenoxa Carticaine, 2-Chloroprocaine Hydrochloride, Cocaethyl mide, Chlortetracycline, Dehydroemetime, Dibromopro ene, Cocaine, Cyclomethycaine, Dibucaine Hydrochlo 45 pamidine, Diloxamide, DiphetarSone, Emetine, Fumagil ride, Dimethisoquin, Dimethocaine, Diperodon Hydro lin, Glaucarubin, Glycobiarsol, 8-Hydroxy-7-iodo-5- chloride, Dyclonine, Ecgonidine, Ecgonine, Ethyl quinolinesulfonic Acid, Iodochlorhydroxyquin, Aminobenzoate, Ethyl Chloride, Etidocaine, Etoxadrol, Iodoquinol Paromomycin, Phanquinone, Phenarsone Sul B-Eucaine, Euprocin, Fenalcomine, Fomocaine, Hexobar foxylate, Polybenzarsol, Propamidine, Quinfamide Sec bital, Hexylcaine Hydrochloride, Hydroxydione Sodium, 50 nidazole, Sulfarside, Teclozan, Tetracycline. Thiocarbam Hydroxyprocaine, Hydroxytetracaine, Isobutyl p-Ami izine. Thiocarbarsone and Tinidazole. nobenzoate, Kentamine, Leucinocaine Mesylate, LeVoxa 22) Antiandrogens such as Bifluranol, Cyoctol, Cyproterone, drol, Lidocaine, Mepivacaine, Meprylcaine Hydrochlo Delmadinone Acetate, Flutamide, Nilutamide and Oxen ride, Metabutoxycaine Hydrochloride, Methohexital dolone. Sodium, Methyl Chloride, Midazolam, Myrtecaine, Nae 55 23) Antianginals such as Acebutolol, Alprenolol, Amio paine, Octacaine, Orthocaine, Oxethazaine, Parethox darone, Amlodipine, Arotinolol, Atenolol, Bepridil, ycaine, Phenacaine Hydrochloride, Phencyclidine, Phe Bevantolol, Bucumolol, Bufetolol, Bufuralol, Bunitrolol, nol, Piperocaine Piridocaine, Polidocanol, Pramoxine, Bupranolol, Carozolol, Carteolol, Carvedilol Celiprolol, Prilocaine, Procaine, Propanidid, Propanocaine, Propara Cinepazet Maleate, Diltiazem, Epanolol, Felodipine, Gal caine, Propipocaine, Propofol, Propoxycaine HVdro 60 lopamil, Imolamine, Indenolol, Isosorbide Dinitrate, Isra chlonde, Pseudococaine, Pyrrocaine, Quinine Urea dipine, Limaprost, Mepindolol, Metoprolol, Molsidom Hydrochloride, Risocaine, Salicyl Alcohol, Tetracaine ine, Nadolol, Nicardipine, Nifedipine, Nifenalol, Hydrochloride. Thialbarbital. Thimylal. Thiobutabarbital, Nilvadipine, Nipradillol, Nisoldipine, Nitroglycerin, Thiopental Sodium, Tolycaine, Trimecaine and Zolamine. Oxprenolol, Oxyfedrine, OZagrel, Penbutolol, Pen 13) Anorectics such as Aminorex, Amphecloral, Amphet 65 taerythritol Tetranitrate, Pindolol, Pronethalol, Propra amine, BenZphetamine, Chlorphentermine, Clobenzorex, nolol, Sotalol, Terodiline, Timolol, Toliprolol and Vera Cloforex, Clortermine, Cyclexedrine, Dextroamphet pamil. US 7,026,360 B1 9 10 24) Antiarrhythmics such as Acebutolol, Acecainide imepicycline, Phenethicillin Potassium, Piperacillin, Piv Adenosine, Ajmaline, Alprenolol, Amiodarone, Amo ampicillin, Propicillin, Quinacillin, Sulbenicillin, proxan, Aprindine, Arotinolol, Atenolol, Bevantolol. Talampicillin, Temocillin and Ticarcillin; Bretylium, Tosylate, Bucumolol, Bufetolol, Bunaftine, Lincosamides such as Clindamycin and Lincomycin; Bunitrolol, Bupranolol Butidrine Hydrochloride, Buto Macrollides such as Azithromycin, Carbomycin, Clarithro bendine, Capobenic Acid, Carazolol, Carteolol, Cifenline, mycin, Erythromycin, Erythromycin Acistrate, Erythro Cloranolol, Disopyramide, Encainide, Esmolol, Flecain mycin Estolate, Erythromycin Glucoheitonate, Erythro ide, Gallopamil, Hydroquinidine, Indecainide, Indenolol. mycin Lactobionate, Erythromycin Propionate, Ipratropium Bromide, Lidocaine, Lorajmine, Lorcainide, Erythromycin Stearate, Josamycin, Leucomycins, Mide Meobentine, Metipranolol, Mexiletine, Moricizine, 10 camycins, Miokamycin, Oleandomycin, Primycin, Roki Nadoxolol, Nifenalol, Oxprenolol, Penbutolol, Pindolol, tamycin, Rosaramicin, Roxithromycin, Spiramycin and Pirmenol, Practolol, Prajmaline, Procainamide Hydro Troleandomycin; chloride, Pronethalol Propafenone, Propranolol, Pyrino Polypeptides such as Amphomycin, Bacitracin, Capreomy line, Quinidine Sulfate, Quinidine, Sotalol, Talinolol, cin, Colistin, Enduracidin, Enviomycin, Fusafungine, Timolol, Tocainide, Verapamil, Vicquidil, and Xibenolol. 15 Gramicidin(s), Gramicidin S. Mikamycin, Polymyxin, 25) Antiarteriosclerotics such as Pyridinol Carbamate. Polymyxin B-Methanesulfonic Acid, Pristinamycin, Ris 26) Antiarthritic/Antirheumatics such as Allocupreide tocetin, Teicoplanin, Thiostrepton, Tuberactinomycin, Sodium, Auranofin, Aurothioglucose, Aurothioglycanide, Tyrocidine, Tyrothricin, Vancomycin, Viomycin, Viomy Azathioprine, Calcium 3-Aurothio-2-propanol-1-sul cin Pantothenate, Virginiamycin and Zinc Bacitracin; fonate, Chloroquine, Clobuzarit, Cuproxoline, Diacerein, Tetracyclines such as Apicycline, Chlortetracycline, Clo Glucosamine, Gold Sodium Thiomalate, Gold Sodium mocycline, Demeclocycline, Doxycycline, Guamecy Thiosulfate, Hydroxychloroquine, KebuZone, Lobenzarit, cline, Lymecycline, Meclocycline, Methacycline, Melittin, Methotrexate, Myoral and Penicillamine. Minocycline, Oxytetracycline, Penimepicycline, Pipacy 27) Antibacterial (antibiotic) drugs, including: cline, Rolitetracycline, Sancycline, Senociclin and Tetra Aminoglycosides Such as Amikacin, Apramycin, Arbekacin, 25 cycline; and Bambermycins, Butirosin, Dibekacin, Dihydrostreptomy other antibiotics Such as Cycloserine, Mupirocin and cin, Fortimicin(s), Gentamicin, Isepamicin, Kanamycin, Tuberin. Micronomicin, Neomycin, Neomycin Undecylenate, 28) Antibacterial drugs (synthetic), including: Netilmicin, Paromomycin, Ribostamycin, Sisomicin, 2.4-Diaminopyrimidines such as Brodimoprim, TetroXoprim Spectinomycin, Streptomycin, Streptonicozid and Tobra 30 and Trimethoprim; mycin; Nitrofurans such as Furaltadone, Furazolium Chloride, Amphenicols such as AZidamfenicol, Chloramphenicol, Nifuradene, Nifuratel, Nifurfoline, Nifurpirinol, Niturpra Chloramphenicol Palmitate, Chloramphenicol Pantothen Zine, Nifurtoinol and Nitrofurantoin: ate, Florfenicol and Thiamphenicol; Quinolones and Analogs such as Amifloxacin, Cinoxacin, Ansamycins such as Rifamide, Rifampin, Rifamycin and 35 Ciprofloxacin, Difloxacin, Enoxacin, Fleroxacin, Flume Rifaximin. quine, Lomefloxacin, Miloxacin, Nalidixic Acid, Nor B-Lactams including: floxacin, Ofloxacin, Oxolinic Acid, Pefloxacin, Pipemidic Carbapenems such as Imipenem; Acid, Piromidic Acid, Rosoxacin, Temafloxacin and Cephalosporins such as Cefaclor Cefadroxil, Cefamandole, Tosufloxacin; Cefatrizine, Cefazedone, Cefazolin, Cefixime, Cef 40 Sulfonamides such as Acetyl Sulfamethoxypyrazine, Acetyl menoxime, Cefodizime, Cefonicid, Cefoperazone, Cefo Sulfisoxazole, AZosulfamide, Benzylsulfamide, Chloram ranide, Cefotaxime, Cefotiam, Ce?pimizole, Ce?piramide, ine-B, Chloramine-T, Dichloramine T. Formosulfathiaz Cefpodoxime Proxetil, Cefroxadine, Cefsulodin, Ceftazi ole, N°Formylsulfisomidine, N'-(3-D-Glucosylsulfanil dime, Cefteram, Ceftezole, Ceftibuten, Ceftizoxime, amide, Mafenide-4'-(Methylsulfamoyl) sulfanilanilide, Ceftriaxone, Cefuroxime, Cefuzonam, Cephacetrile 45 p-Nitrosulfathiazole, Nopryisulfamide, Phthalyisulfaceta Sodium, Cephalexin, Cephaloglycin, Cephaloridie, mide, Phthalylsulfathiazole, Salazosulfadimidine, Succi Cephalosporin, Cephalothin, Cephapirin Sodium, Ceph nylsulfathiazole, Sulfabenzamide, Sulfacetamide, Sul radine and Piveefalexin; fachlorpyridazine, Sulfachrysoidine Sulfacytine, Cephamycins such as CefbuperaZone, Cefnetazole, Cefni Sulfadiazine, Sulfadicramide, Sulfadimethoxine, Sulfa nox, Cefotetan and Cefoxitin; 50 doxine, Sulfaethidole, Sulfaguanidine, Sulfaguanol, Sul Monobactams such as Aztreonam, Carumonam and Tige falene, Sulfaloxic Acid, Sulfamerazine, Sulfameter, Sul monam, famethazine, Sulfamethizole, Sulfamethomidine, Oxacephems such as Flomoxef and Moxolactam: Sulfamethoxazole, Sulfamethoxypyridazine, Sulfame Penicillins such as Amidinocillin, Amdinocillin, Pivoxil, trole, Sulfamidochrysoidine, Sulfamoxole, Sulfanilamide, Amoxicillin, Ampicillin, Apalcillin, Aspoxicillin, AZi 55 Sulfanilamidomethanesulfonic Acid Triethanolamine docillin, AZlocillin, Bacampicillin, Benzylpenicillinic Salt, 4-Sulfanilamidosalicylic Acid N-Sulfanilylsulfanil Acid, Benzylpenicillin Sodium, Carbenicillin, Carfecillin amide, Sulfanilylurea, N-Sulfanilyl-3,4-xylamide, Sul Sodium, Carindacillin, Clometocillin, Cloxacillin, Cycla fanitran, Sulfaperine, Sulfaphenazole, Sulfaproxyline, cillin, Dicloxacillin, Diphenicillin Sodium, Epicillin, Fen Sulfapyrazine, Sulfapyridine, Sulfasomizole, Sulfasy benicillin, Floxacillin, Hetacillin, Lenampicillin, 60 mazine, Sulfathiazole, Sulfathiourea, Sulfatolamide, Metampicillin, Methicillin Sodium, Mezlocillin, Nafcillin Sulfisomidine and Sulfisoxazole; Sodium, Oxacillin, Penamecillin, Penethamate, Hydrio Sulfones such as Acedapsone, Acediasulfone, Acetosulfone dide, Penicillin G Benethamine, Penicillin G BenZathine, Sodium, Dapsone, Diathymosulfone, Glucosulfone Penicillin G Benzhydrylamine, Penicillin G Calcium, Sodium, Solasulfone, Succisulfone, Sulfanilic Acid, Penicillin G-Hydrabamine, Penicillin G Potassium, Peni 65 p-Sulfanilylbenzylamine, p.p'-Sulfonyldianiline-N, cillin G Procaine, Penicillin N, Penicillin O, Penicillin V, N'digalactoside, Sulfoxone Sodium and Thiazolsulfone: Penicillin V BenZathine, Penicillin V Hydrabamine, Pen and US 7,026,360 B1 11 12 others such as Clofoctol, Hexedine, Methenamine, Meth Pyrrolidones such as Cotinine, Rolicyprine and Rolipram; enamine Anhydromethylene-citrate, Methenamine Hip Tetracyclics such as Maprotiline, Metralindole, Mianserin purate, Methenamine Mandelate, Methenamine Sulfosali and Oxaprotiline, Tricyclics such as Adinazolam, Ami cylate, Nitroxoline and Xibornol. triptyline, Amitriptylinoxide, Amoxapine, Butriptyline, 29) Anticholinergics such as Adiphenine Hydrochloride, Clomipramine, Demexiptiline, Desipramine, Dibenzepin, Alverine, Ambutonomium Bromide, Aminopentamide, Dimetacrine, Dothiepin, Doxepin, Fluacizine Imi Amixetrine, Amprotropine, Phosphate, Anisotropine pramine. Imipramine N-Oxide prindole, Lofepramine, Methylbromide, Apoatropine, Atropine, Atropine N-OX Melitracen, Metapramine, Nortriptyline, Noxiptilin, ide, Benactyzine, Benapryzine, Benzetimice, Benzilo Opipramol, Pizotyline, Propizepine, Protriptyline, Quinu nium Bromide, Benztropine Mesylate, Bevonium Methyl 10 pramine, Tianeptine and Trimipramine; and Sulfate, Biperiden, Butropium Bromide, N-Butylscopola others such as Adrafinil, Benactyzine, Bupropion, Butacetin, mmomium Bromide, BuZepide, Camylofine, Caramiphen Deanol, Deanol Aceglumate, Deanol Acetamidobenzoate, Hydrochloride, Chlorbenzoxamine, Chlorphenoxamine, Dioxadrol, Etoperidone, Febarbamate, Femoxetine, Fen Cimetropium Bromide, Clidinium Bromide, Cyclodrine, pentadiol, Fluoxetine, Fluvoxamine, Hematoporphyrin, Cyclonium Iodide, Cycrimine Hydrochloride, Dep 15 Hypercinin, Levophacetoperane, Medifoxamine, tropine, Dexetimide, Dibutoline Sulfate, Dicyclomine Minaprine, Moclobemide, Oxaflozane, Piberaline, Prolin Hydrochloride, Diethazine, Dimerine, Dihexyverine, tane, Pyrisuccideanol, Rubidium Chloride, Sulpiride, Sul Diphemanil Methylsulfate, N-(1,2-Diphenylethyl)nicoti topride, Teniloxazine, Thozalinone, Tofenacin, namide, Dipiproverine, Diponium Bromide, Emepronium Toloxatone, Tranylcypromine, L-Tryptophan, Viloxazine Bromide, Endobenzyline Bromide, Ethopropazine, Ethy and Zimeldine. benztropine, Ethylbenzhydramine, Etomidoline, Eucatro 32) Antidiabetics, Including: pine, Fenpiverinium Bromide, Fentonium Bromide, Biguanides such as Buformin, Metformin and Phenformin; Flutropium Bromide, Glycopyrrolate, Heteronium Bro Hormones such as Glucagon, Insulin, Insulin Injection, mide, Hexocyclium Methyl Sulfate, Homatropine, Hyos Insulin Zinc Suspension, Isophane Insulin Suspension, cyamine, pratropium Bromide, Isopropamide, Levome 25 Protamine Zinc Insulin Suspension and Zinc Insulin Crys pate, Mecloxamine, Mepenzolate Bromide, Metcaraphen, tals; Methantheline Bromide, Methixene, Methscopolamine Sulfonylurea derivatives such as Acetohexamide, 1 Butyl Bromide, Octamylamine, Oxybutynin Chloride, 3-metanilylurea, Carbutamide, Chlorpropamide, Glib Oxyphencyclimine, Oxyphenonium Bromide, Pentapip ornuride, Gliclazide, Glipizide, Gliquidone, Glisoxepid, eride Penthienate Bromide, Phencarbamide, Phengluta 30 Glyburide, Glybuthiazol(e), Glybuzole, Glyhexamide, rimide, Pipenzolate Bromide, Piperidolate, Piperilate, Glymidine, Glypinamide, Phenbutamide, Tolazamide, Poldine Methysulfate, Pridinol, Prifinium Bromide, Pro Tolbutamide and Tolcyclamide; and others such as Acar cyclidine Propantheline Bromide, Propenzolate, Propyro bose, Calcium Mesoxalate and Miglitol. mazine, Scopolamine, Scopolamine N-Oxide, Stilonium 33) Antidiarrheal drugs such as Acetyltannic Acid, Albumin Iodide, Stramonium, Sultroponium Thihexinol, Thiphe 35 Tannate, Alkofanone, Aluminum Salicylates-Basic, Cat namil, Tiemonium Iodide, Timepidium Bromide, Tiqui echin, Difenoxin, Diphenoxylate, Lidamidine, Loperam Zium Bromide, Tridihexethyl Iodide, Trihexyphenidyl ide, Mebiquine, Trillium and Uzarin. Hydrochloride, Tropacine, Tropenzile, Tropicamide, Tro 34) Antidiuretics such as Desmopressin, Fely pressin, spium Chloride, Valethamate Bromide and Xeny tropium Lypressin, Ornipressin, Oxycinchophen, Pituitary-Poste Bromide. 40 rior, Terlipressin and Vasopressin. 30) Anticonvulsants such as Acetylpheneturide, Albutoin, 35) Antiestrogens such as Delmadinone Acetate, Ethamox Aloxidone, Aminoglutethimide, 4-Amino-3-hydroxybu ytriphetol, Tamoxifen and Toremifene. tyric Acid, Atrolactamide, Beclamide, Buramate, Calcium 36) Antifungal drugs (antibiotics), including: Bromide, Carbamazepine, Cinromide, Clomethiazole, Polyenes such as Amphotericin-B, Candicidin, Dermostatin, Clonazepam, Decimemide, Diethadione, Dimethadione, 45 Filipin, Fungichromin, Hachimycin, Hamycin, Lucenso Doxenitoin, Eterobarb, Ethadione, Ethosuximide, Etho mycin, Mepartricin, Natamycin, Nystatin, Pecilocin and toin, Fluoresone 5-Hydroxytryptophan, Lamotrigine, Perimycin; and Magnesium Bromide Magnesium Sulfate, Mephenytoin, others such as AZaserine, Griseofulvin, Oligomycins, Neo Mephobarbital, Metharbital, Methetoin Methsuximide, mycin Undecylenate, Pyrrolnitrin, Siccanin, Tubercidin 5-Methyl-5-(3-phenanthryl)hydantoin, 3-Methyl-5-phe 50 and Viridin. nylhydantoin, Narcobarbital, Nimetazepam, Nitrazepam 37) Antifungal drugs (synthetic), including: Paramethadione, Phenacemide, Phenetharbital, Phenetu Allylamines such as Naftifine and Terbinafine; ride Phenobarbital, Phenobarbital Sodium, Phensuximide, Imidazoles such as Bifonazole, Butoconazole, Chlordantoin, Phenylmethylbarbituric Acid, Phenytoin, Phethenylate Chlormidazole, Cloconazole, Clotrimazole, Econazole, Sodium, Potassium Bromide, Primidone, Progabide, 55 Enilconazole, Fenticonazole, Isoconazole, Ketoconazole, Sodium Bromide, Solanum, Strontium Bromide, Miconazole, Omoconazole, Oxiconazole Nitrate, Sul Suclofenide, Sulthiame, Tetrantoin, Trimethadione, Valp conazole and Tioconazole; roic Acid, Valpromide, Vigabatrin and Zonisamide. Triazoles such as Fluconazole, Itraconazole and Tercona 31) Antidepressants, including: Zole; and others such as Acrisorcin, Amorolfine, Biphe Bicyclics Such as Binedaline, CaroXaZone, Citatopram, 60 namine, Bromosalicylchloranilide, Buclosamide, Cal Dimethazan, Indalpine, Fencamine, Indeloxazine Hydro cium Propionate, Chlorehenesin, Ciclopirox, Cloxyquin, chloride, Nefopam, Nomifensine, Oxitriptan, Oxypertine, Coparaffinate, Diamthazole Dihydrochloride. Exalamide, Paroxetine, Sertraline. Thiazesim, Trazodone and Flucytosine, Halethazole, Hexetidine, Loflucarban, Nifu Zometapine; ratel, Potassium Iodide, Propionic Acid, Pyrithione, Sali Hydrazides/Hydrazines such as Benmoxine, Iproclozide, 65 cylanilide, Sodium Propionate, Sulbentine, Tenonitrozole, Iproniazid, Isocarboxazid, Nialamide, Octamoxin and Tolciclate, Tolindate, Tolnaftate, Triacetin, Ujothion, Phenelzine; Undecylenic Acid and Zinc Propionate. US 7,026,360 B1 13 14 38) Antiglaucoma drugs such as Acetazolamide. Befunolol. filolol, Carazolol, Carteolol, Carvedilol, Celiprolol, Ceta Betaxolol, Bupranolol, Carteolol, Dapiprazole, Dichlor molol, Epanolol, Indenolol, Mepindolol, Metipranolol, phenamide, Dipivefrin, Epinephrine, Levobunolol, Met Metoprolol, Moprolol, Nadolol, Nipradillol, Oxprenolol, hazolamide, Metipranolol, Pilocarpine, Pindolol and Penbutolol, Pindolol, Propranolol, Talinolol, Tertatolol, Timolol. Timolol and Toliprolol; 39) Antigonadotropins such as Danazol, Gestrinone and Benzothiadiazine derivatives such as Althiazide, Bendrof Paroxypropione. lumethiazide, Benzthiazide, Benzylhydrochlorothiazide, 40) Antigout drugs such as Allopurinol, Carprofen, Colchi Buthiazide, Chlorothiazide, Chlorthalidone, Cyclopenthi cine, Probenecid and Sulfinpyrazone. azide, Cyclothiazide, Diazoxide, Epithiazide, Ethiazide, 41) Antihistamines, including: Alkylamine derivatives Such 10 Fenguizone, Hydrochlorothiazide, Hydroflumethiazide, as Acrivastine, Bamipine, Brompheniramine, Chlorphe Methyclothiazide Meticrane, Metolazone, Paraflutizide, niramine, Dimethindene, Metron S. Pheniramine, Pyrrob Polythiazide, Tetrachlormethiazide, and Trichlormethiaz utamine. Thenaldine, Tolpropamine and Triprolidine; ide; Aminoalkyl ethers such as Bietanautine, Bromodiphenhy N-Carboxyalkyl (petide/lactam) derivatives such as Alace dramine, Carbinoxamine, Clemastine, Diphenylpyraline, 15 pril, Captopril, Cilazapril, Delapril, Enalapril, Enalaprilat, Doxylamine, Embramine, Medrylamine, Mephenhy Fosinopril, Lisinopril, Moveltipril, Perindopril, Quinapril dramine, p-Methyldiphenhydramine, Orphenadrine, Phe and Ramipril; nyltoloxamine, Piprinhydrinate and Setasine; Dihydropyridine derivatives such as Amlodipine, Fello Ethylenediamine derivatives such as Alloclamide, p-Bro dipine, Isradipine, Nicardipine, Nifedipine, Nilvadipine, mtripelennamine, Chloropyramine, Chlorothen, Histapy Nisoldipine and Nitrendipine; rrodine, Methafurylene, Methaphenilene, Methapyrilene, Guanidine derivatives such as Bethanidine, Debrisoquin, Phenbenzamine, Pyrilamine, Talastine, Thenyldiamine, Guanabenz, Guanacline, Guanadrel, GuanaZodine, Thonzylamine Hydrochloride, Tripelennamine and Zola Guanethidine, Guanfacine, Guanochlor, Guanoxabenz mine; and Guanoxan; Piperazines such as Cetirizine, Chlorcyclizine, Cinnarizine, 25 Hydrazines and phthalazines such as Budralazine, Cadrala Cilocinizine and Hydroxyzine; zine, Dihydralazine, Endralazine, Hydracarbazine, Tricyclics, including: Hydralazine, Pheniprazine, Pildralazine and Todralazine: Phenothiazines Such as Ahistan, Etymemazine, Hydrox Imidazole derivatives such as Clonidine, Lofexidine, Phen yzine, N-Hydroxyethylpromethazine Chloride, Iso tolamine, Tiamenidine and Tolonidine; promethazine, Mequitazine, Promethazine, Pyrathiazine 30 Quaternary ammonium compounds AZamethonium Bro and Thiazinamium Methyl Sulfate; and others such as mide, Chlorisondamine Chloride, Hexamethonium, Pen AZatadine, Clobenzepam, Cyproheptadine, Deptropine, tacynium Bis(methyl sulfate), Pentamethonium Bromide, Isothipendyl, Loratadine and Prothipendyl; and Pentolinium Tartate, Phenactopinium Chloride and Tri other antihistamines such as Antazoline, Astemizole AZelas methidinium Methosulfate, tine Cetoxime, Clemizole, Clobenztropine, Diphenazo 35 Quinazoline derivatives such as AlfuZosin, BunaZosin, DOX line, Diphenhydramine, Mebhydroline, Phenindamine, aZosin, PraZosin, Terazosin and TrimaZosin; Terfenadine and Tritoqualine. Reserpine derivatives such as Bietaserpine Deserpidine, 42) Antihyperlipoproteinemics, including: Rescinnamine, Reserpine and Syrosingopine; Aryloxalkanoic acid derivatives such as Beclobrate, Bezafi Sulfonamide derivatives such as Ambuside, Clopamide, brate, Binifibrate, Ciprofibrate, Clinofibrate, Clofibrate, 40 Furosemide, Indapamide, QuinethaZone, Tripamide and Clofibric Acid, Etofibrate, Fenofibrate, Gemfibrozil, Xipamide; and Nicofibrate, Pirifibrate, Ronifibrate, Simfibrate and others such as Ajmaline, Y-Aminobutyric Acid, Bufeniode, Theofibrate; Chlorthalidone, Cicletanine, Ciclosidomine, Crypte Bile acid sequesterants such as Cholestyramine Resin, namine Tannates, Fenoldopam, Flosequinan, Indoramin, Colestipol and Polidexide: 45 Ketanserin, Mebutamate, Mecamylamine, Methyldopa, HMG CoA reductase inhibitors such as Lovastatin, Pravas Methyl 4-Pyridyl-Ketone Thiosemicarbarzone, Metola tatin Sodium and Simvastatin: Zone, Minoxidil, Muzolimine, Pargyline, Pempidine, Nicotinic acid derivatives Aluminum Nicotinate, Acipimox, Pinacidil, Piperoxan, Primaperone, Protoveratrines, Niceritrol, Nicoclonate, Nicomol and Oxiniacic Acid; Raubasine, Rescimetol, Rilmenidene, Saralasin, Sodium Thyroid hormones and analogs such as EtiroXate, Thyro 50 Nitroprusside, Ticrynafen, Trinmethaphan, Camsylate, propic Acid and Thyroxine; and Tyrosinase and Urapidil. others such as Acifran, AZacosterol, Benfluorex, B-Benzal butyramide, Carnitine, Chondroitin Sulfate, Clomestrone, 44) Antihyperthyroids such as 2-Amino-4-methylthiazole, Dietaxtran, Dextran Sulfate Sodium, 5,8,11,14, 17-Eicosa 2-Aminothiazole Carbimazole 3,5-Dibromo-L-tyrosine pentaenoic Acid, Eritadenine, Furazabol, Meglutol, Meli 55 3,5-Diiodotyrosine, Hinderin, Iodine, Iothiouracil Methi namide, Mytatrienediol, Ornithine, Y-Oryzanol, Pan mazole Methylthiouracil, Propylthiouracil, Sodium Per tethine, Pentaerythritol Tetraacetate, chlorate. Thibenzazoline. Thiobarbital and 2-Thiouracil. O-Phenylbutyramide, Pirozadil, Probucol, C.-Sitosterol, 45) Antihypotensive drugs such as Amezinium Methyl Sul Sultosilic Acid, Piperazine Salt, Tiadenol, Triparanol and fate, Angiotensin Amide, Dimetofrine, Dopamine, Etife Xenbucin. 60 lmin, Etilefrin, Gepefine, Metaraminol, Midodrine, Nore 43) Antihypertensive drugs, including: pinephrine, Pholedrine and Synephrine. Arylethanolamine derivatives Such as Amosulalol, 46) Antihypothyrold drugs such as Levothyroxine Sodium, Bufuralol, Dilevalol, Labetalol, Pronethalol, Sotalol and Liothyronine, Thyroid, Thyroidin, Thyroxine, Tiratricol Sulfinalol; and TSH. Aryloxypropanolamine derivatives such as Acebutolol. 65 47) Anti-Inflammatory (non-steroidal) drugs, including: Alprenolol. Arotinolol, Atenolol, Betaxolol, Bevantolol, Aminoaryicarboxylic acid derivatives such as Enfenamic Bisoprolol, Bopindolol, Bunitrolol, Bupranolol. Buto Acid, Etofenamate, Flufenamic Acid, Isonixin, Meclofe US 7,026,360 B1 15 16 namic Acid, Mefenamic Acid. Niflumic Acid, Talniflu 51) Antineoplastic drugs in including: Alkylating agents, mate, Terofenamate and Tolfenamic Acid; including: Arylacetic acid derivatives such as Acemetacin) Alclofenac, Alkyl sulfonates such as Busulfan, Improsulfan and Pipo Amfenac, Bufexamac, Cinmetacin, Clopirac, Diclofenac Sulfan; Sodium, Etodolac, Felbinac, Fenclofenac, Fenclorac, AZiridines Such as BenZodepa, Carboqune, Meturedepa and Fenclozic Acid, Fentiazac, Glucametacin, Ibufenac, Uredepa; Ethylenimines and methylmelamines Such as Indomethacin, IsofeZolac, ISOXepac, LonaZolac, Metiaz Altretamine, Triethylenemelamine, Triethylenephos inic Acid, Oxametacine, Proglumetacin, Sulindac, Tiara phoramide, Triethylenethiophosphoramide and Trimethy mide, Tolimetin and Zomepirac: lolmelamine; Arylbutyric acid derivatives such as Bumadizon) Butibufen) 10 Nitrogen mustards such as Chlorambucil, Chlornaphazine, Fenbufen and Xenbucin; Cyclophosphamide, Estramustine, Ifosfamide, Mechlore Arylcarboxylic acid such as Clidanac Ketorolac and Tino thamine, Mechlorethamine Oxide Hydrochloride, Mel ridine; phalan, Novembichin, Phenesterine, Prednimustine, Tro Arylpropionic acid derivatives such as Alminoprofen, fosfamide and Uracil Mustard; Benoxaprofen Bucloxic Acid, Carprofen, Fenoprofen, 15 Flunoxaprofen, Flurbiprofen, Ibuprofen, Ibuproxam, Nitrosoureas such as Carmustine, Chlorozotocin, Fotemus Indoprofen, Ketoprofen, Loxoprofen, Miroprofen, tine, Lomustine Nimustine and Ranimustine; and Naproxen, Oxaprozin, Piketoprofen, Pirprofen, Pranopro others such as Dacarbazine; Mannomustine, Mitobronitol, fen, Protizinic Acid. Suprofen and Tiaprofenic Acid; Mitolactol and Pipobroman; Pyrazoles such as Difenamizole and Epirizole; Antibiotics such as Aclacinomycins, Actinomycin F1, Pyrazolones such as ApaZone, BenZpiperylon, Feprazone, Anthramycin, AZaserine, Bleomycins, Cactinomycin, Mofebutazone, Morazone, Oxyphenbutazone, Phenylb Carubicin, Carzinophilin, Chromomycins, Dactinomycin, Daunorubicin, 6-Diazo-5-oxo-L-norleucine, Doxorubi utaZone, PipebuZone, PropyphenaZone, RamifenaZone, cin, Epirubicin, Mitomycins, Mycophenolic Acid, SuxibuZone and Thiazolinobutazone; Nogalamycin, Olivomycins, Peplomycin, Plicamycin, Salicylic acid derivatives such as Acetaminosalol, Aspirin, 25 Benorylate, Bromosaligenin, Calcium Acetylsalicylate, Porfiromycin, Puromycin, Streptonigrin, Streptozocin, Diflunisal, Etersalate, Fendosal, Gentisic Acid, Glycol Tubercidin, Ubenimex, Zinostatin and Zorubicin; Salicylate, Imidazole Salicylate, Lysine Acetylsalicylate, Antimetabolites, including: Mesalamine, Morpholine Salicylate, 1-Naphthyl Salicy Folic acid analogs such as Denopterin Methotrexate, Pterop late, Olsalazine, Parsalmide, Phenyl Acetylsalicylate, 30 terin and Trimetrexate; Phenyl Salicylate, Salacetamide, Salicylamine, O-Acetic Purine analogs such as Fludarabine, 6-Mercaptopurine, Acid, Salicylsulfuric Acid, Salsalate and Sulfasalazine: Thiamiprine and Thioguanine; and Thiazinecarboxamides Such as Droxicam, Isoxicam, Piroxi Pirymidine analogs such as Ancitabine, AZacitidine, cam and Tenoxicam, and 6-AZauridine, Carmofur, Cytarabine, Doxifluridine, others such as e-Acetamidocaproic Acid, S-Adenosylme 35 Enocitabine, Floxuridine, Fluorouracil and Tegafur, thionine, 3-Amino-4-hydroxybutyric Acid Amixetrine, Enzymes Such as L-Asparaginase; and Bendazac, BenZydamine, Bucolome, Dilfenpiramide, others such as Aceglatone, Amsacrine, Bestrabucil, Bisant Ditazol, EmorfaZone, GuaiaZulene, Nabumetone, Nime rene, Carboplatin, Cisplatin, Defosfamide, Demecolcine, Sulide, Orgotein, Oxaceprol, Paranyline, Perisoxal, Diaziguone, Eflornithine, Elliptinium Acetate, Etoglucid, Pifoxime, ProquaZone, Proxazole and Tenidap. 40 Etoposide, Gallium Nitrate, Hydroxyurea, Interferon-C. 48) Antimalarial drugs such as Acedapsone, Amodiaquin, interferon-B, Interferon-Y, Interleukin-2, Lentinan, Arteether, Artemether, Artemisinin, Artesunate, Bebeer Lonidamine, MitoguaZone Mitoxantrone, Mopidamol, ine, Berberine, Chirata, Chlorguanide, Cinchona, Cin Nitracrine Pentostatin, Phenamet, Pirarubicin, Podophyl chonidine, Cinchonine, Cycloguanil, Gentiopicrin, Halo linic, Acid, 2-Ethylhydrazide, Procarbazine, PSKR), fantrine, Hydroxychloroquine, Mefloquine 45 Razoxane, Sizofiran, Spirogermanium, Taxol. Teniposide, Hydrochloride, 3-Methylarsacetin, Pamaquine, Plas TenuaZonic Acid, Triaziquone, 2 2.2"-Trichlorotriethy mocid Primaquine, Pyrimethamine, Quinacrine, Quinine, lamine, Urethan, Vinblastine, Vincristine and Vindesine. Quinine Bisulfate, Quinine Carbonate, Quinine Dihydro 52) Antineoplastic (hormonal) drugs, including: Androgens bromide, Quinine Dihydrochloride, Quinine Ethylcarbon Such as Calusterone, Dromostanolone Propionate. Epi ate, Quinine Formate, Quinine Gluconate, Quinine 50 tiostanol Mepitiostane and Testolactone; Hydriodide, Quinine Hydrochloride, Quinine Salicylate, Antiadrenals such as Aminoglutethimide Mitotane and Quinine Sulfate, Quinine Tannate, Quinine Urea Hydro TriloStane; Antiandrogens Such as Flutamide and Niluta chloride, Quinocide, Quinoline and Sodium Arsenate Dibasic. mide; and 49) Antimigraine drugs such as Alpiropride, Dihydroergota 55 Antiestrogens such as Tamoxifen and Toremifene. mine, Ergocornine, Ergocorninine, Ergocryptine, Ergot, 53) Antineoplastic adjuncts Including folic acid replenishers Ergotamine, FlumedroXone acetate, Fonazine, Lisuride such as Folinic Acid. Methysergid(e), Oxetorone, Pizotyline and Sumatriptan. 54) Antiparkinsonian drugs such as Amantadine, Benser 50) Antinauseant drugs such as Acetylleucine Monoethano azide, Bietanautine, Biperiden, Bromocriptine, Budipine, lamine, Alizapride, BenZquinamide, Bietanautine, Bro 60 Carbidopa, Deprenyl, Dexetimide, Diethazine, Droxi mopride, Buclizine Chlorpromazine, Clebopride, Cycliz dopa, Ethopropazine, Ethylbenzhydramine, Levodopa, ine, Dimenhydrinate, Diphenidol, Domperidone, Naxagolide, Pergolide, Piroheptine, Pridinol, Prodipine, Granisetron, Meclizine, Methallatal, Metoclopramide Terguride Tigloidine and Trihexyphenidyl Hydrochloride. Metopimazine, Nabilone, Ondansetron, Oxypendyl, 55) Antipheochromocytoma drugs such as Metyrosine. Phe Pipamazine, Piprinhydrinate, Prochlorperazine, Scopola 65 noxybenzamine and Phentolamine. mine, Tetrahydrocannabinols. Thiethylperazine. Thio 56) Antipneumocystis drugs such as Eflornithine, Pentami properazine, and Trimethobenzamide. dine and Sulfamethoxazole. US 7,026,360 B1 17 18 57) Antiprostatic hypetrophy drugs such as Gestonorone 66) Antiseborrheic drugs such as Chloroxine 3-O-Lau Caproate, Mepartricin, Oxendolone and Proscar(R). roylpyridoxol Diacetate, Piroctone, Pyrithione, Resorci 58) Antiprotozoal drugs (Leshmania) Such as Antimony nol, Selenium Sulfides and Tioxolone. Sodium Gluconate, Ethylstibamine, Hydroxystilbami 67) Antiseptics, including: dine: N-Methylglucamine, Pentamidine, Stilbamidine and 5 Urea Stibamine. Guanidines such as Alexidine, Ambazone, Chlorhexidine 59) Antiprotozoal drugs (Trichomonas) such as AcetarSone, and Picloxydine: Aminitrozole, Anisomycin, AZanidazole, Forminitrazole, Halogens and halogen compounds such as Bismuth Iodide Furazolidone Hachimycin, Lauroguadine, Mepartricin, Oxide, Bismuth Iodosubgallate, Bismuth Tribromophen Metronidazole, Nifuratel, Nifuroxime, Nimorazole, Sec 10 ate, Bornyl Chloride, Calcium Iodate, Chlorinated Lime, nidazole, Silver Picrate, Tenonitrozole and Timidazole. Cloflucarban, Flurosalan, Iodic Acid, Iodine, Iodine 60) Antiprotozoal drugs (Trypanosma) Such as BenZnidazole Monochloride, Iodine Trichloride, Iodoform, Meth Eflornithine Melarsoprol, Nifurtimox, Oxophenarsine, enamine Tetraiodine, Oxychlorosene, Povidone-Iodine, Hydrochloride, Pentamidine, Propamidine, Puromycin, Sodium Hypochlorite, Sodium Iodate, Symclosene, Thy Quinapyramine, Stilbamidine, Suramin Sodium, Trypan 15 mol Iodide, Triclocarban, Triclosan and Troclosene Potas Red and Tryparsamide. 61) Antipuritics such as Camphors, Cyproheptadine, Dichlo sium; risone, Glycine, Halometasone, 3-Hydroxycamphor, Mercurial compounds such as Hydraroaphen, Meralein Menthol. Mesulphen, Methdilazine, Phenol, Polidocanol, Sodium, Merbromin, Mercuric Chloride, Mercuric Chlo Risocaine, Spirit of Camphor, Thenaldine, Tolpropamine ride Ammoniated, Mercuric Sodium p-Phenolsulfonate, and Trimeprazine. Mercuric Succinimide, Mercuric Sulfide Red, Mercu 62) Antipsoriatic drugs such as Acitretin, Ammonium Sali rophen, Mercurous Acetate, Mercurous Chloride, Mercu cylate, Anthralin, 6-AZauridine, Bergapten(e), Chrysar rous Iodide, Nitromersol, Potassium Tetraiodomercurate obin, Etretinate and Pyrogallol. (II), Potassium Triiodomercurate(II) Solution 63) Antipsychotic drugs, including: 25 Thimerfonate Sodium and Thimerosal; Butyrophenones such as Benperidol, Bromperidol, Droperi Nitrofurans such as Furazolidone, 2-(Methoxymethyl)-5- dol, Fluanisone, Haloperidol, Melperone, Moperone, nitrofuran, Nidroxy Zone, Nifuroxime, Nifurzide and Pipamperone, Spiperone, Timiperone and Trifiuperidol; Nitrofurazone; Phenothiazines Such as Acetophenazine, Butaperazine, Car Phenols such as Acetomeroctol, Bithionol, Cadmium Sali phenazine, Chlorproethazine, Chlorpromazihe, Clospira 30 cylate, Carvacrol, Chloroxylenol, Clorophene, Creosot, Zine, Cyamemazine, Dixyrazine, Fluphenazine, Imiclo Cresol(s), p-Cresol Fenticlor, Hexachlorophene, 1-Naph pazine, Mepazine, Mesoridazine, Methoxypromazine, thyl Salicylate, 2-Naphthyl Salicylate, 2.4.6-Tribromo-m- Metofenazate, Oxaflumazine, Perazine, Pericyazine, Perimethazine, Perphenazine, Piperacetazine, Pipotiaz cresol and 3',4',5-Trichlorosalicylanilide; ine, Prochlorperazine, Promazine, Sulforidazine. Thio 35 Quinolines such as Aminoquinuride, BenZOXiquine, BroX propazate. Thioridazine, Trifluoperazine and Triflupro yduinoline, Chloroxine, Chlorquinaldol, Cloxyquin, Eth mazine; ylhydrocupreine, Euprocin, Halquinol, Hydrastine, 8-Hy Thioxanthenes such as Chlorprothixene, Clopenthixol, Flu droxquinoline, 8-Hydroxquinoline Sulfate and pentixol and Thiothixene; Iodochlorhydroxyquin; and other tricyclics Such as BenZquinamide, Carpipramine, Clo 40 others such as Aluminum Acetate Solution, Aluminum Sub capramine Clomacran, Clothiapine, Clozapine, acetate Solution, Aluminum Sulfate, 3-Amino-4-hy Opipramol, Prothipendyl, Tetrabenazine and Zotepine; droxybutyric Acid, Boric Acid, Chlorhexidine, Chloroa and Zodin, m-Cresyl Acetate, Cupric Sulfate, others such as Alizapride, Amisulpride, Buramate, Fluspir Dibromopropamidine, Ichthammol, Negatol R, Noxytio ilene, Molindone, Penfluridol, Pimozide, Spirilene and 45 lin, Ornidazole, B-Propiolactonex C-Terpineol. Sulpiride. 68) Antispasmodic drugs such as Alibendol, Ambucetamide, 64) Antipyretics Such as Acetaminophen, AcetaminoSalol, Aminopromazine, Apoatropine, Bevonium Methyl Sul Acetanilide, Aconine, Aconite, Aconitine, Alclofenac, fate, Bietamiverine. Butaverine. Butropium Bromide, Aluminum Bis(acetylsalicylate), Aminochlorthenoxazin, N-Butylscopolammonium Bromide, Caroverine, Aminopyrine, Aspirin, Benorylate, BenZydamine, Ber 50 Cimetropium Bromide, Cinnamedrine, Clebopride, Coni berine, p-Bromoacetanilide, BufeXamac, Bumadizon, ine Hydrobromide, Coniine Hydrochloride, Cyclonium Calcium Acetysalicylate, Chlorthenoxazin(e), Choline Iodide, Difemerine, Diisopromine, Dioxaphetyl Butyrate, Salicylate, Clidanac, Dihydroxyaluminum Acetylsalicy Diponium Bromide, Drofenine, Emepronium Bromide, late, Dipyrocetyl, Dipyrone, Epirizole, Etersalate. Imida Ethaverine, Feclemine, Fenalamide, Fenoverine, Ferip Zole Salicylate, Indomethacin, IsofeZolac, p-Lactophe 55 iprane, Fenpiverinium Bromide, Fentonium Bromide, netide, Lysine Acetylsalicylate, Magnesium Flavoxate, Flopropione, Gluconic Acid, Guaiactamine, Acetylsalicylate, Meclofenamic Acid, Morazone, Mor Hydramitrazine, Hymecromone, Leiopyrrole, Mebever pholine Salicylate, Naproxen, Nifenazone, 5'-Nitro-2' ine, Moxaverine, Nafiverine, Octamylamine, Octaverine, propoxyacetanilide, Propoxyacetanilide, Phenacetin, Pentapiperide, Phenamacide Hydrochloride, Phlorogluci Phenicarbazide, Phenocol, Phenopyrazone, PhenylAce 60 nol, Pinaverium Bromide, Piperilate, Pipoxolan Hydro tylsalicylate, Phenyl Salicylate, PipebuZone, Propaceta chloride, Pramiverin, Prifinium Bromide, Properidine, mol, PropyphenaZone, RamifenaZone, Salacetamide, Propivane, Propyromazine, Prozapine, Racefemine, Salicylamide O-Acetic Acid, Sodium Salicylate, Sulfami Rociverine, Spasmolytol, Stilonium Iodide, Sultropo pyrine, Tetrandrine and Tinoridine. nium, Tiemonium Iodide, Tiquizium Bromide, Tiropra 65) Antirickettsial drugs such as p-Aminobenzoic Acid, 65 mide, Trepibutone, Tricromyl, Trimebutine, N,N-1 Trim Chloramphenicol, Chloramphenicol Palmitate, Chloram ethyl-3,3-diphenyl-propylamine, TropenZile, Trospium phenicol Pantothenate and Tetracycline. Chloride and Xeny tropium Bromide. US 7,026,360 B1 19 20 69) Antithrombotic drugs such as Anagrelide, Argatroban, 77) Bronchodilators, including: Cilostazol, Daltroban, Defibrotide, Enoxaparin, Fraxi Ephedrine derivatives such as Albuterol, Bambuterol, parine R, Indobufen, Lamoparan, OZagrel, Picotamide, Bitolterol Carbuterol, Clenbuterol, Clorprenaline, Diox Plafibride, Tedelparin, Ticlopidine and Triflusal. ethedrine, Ephedrine Epinephrine, Eprozinol, Etafedrine, 70) Antitussive drugs such as Alloclamide, Amicibone, Ethylnorepinephrine, Fenoterol, Hexoprenaline, Isoet Benproperine, Benzonatate, Bibenzonium Bromide, Bro harine, Isoproterenol, Mabuterol, Metaproterenol, N-Me moform, Butamirate. Butethamate, Caramiphen thylephedrine, Pirbuterol, Procaterol, Protokylol, Repro Ethanedisulfonate, Carbetapentane, Chlophedianol, terol, Rimiterol, Soterenol, Terbuterol and Tulobuterol: Clobutinol, Cloperastine, Codeine, Codeine Methyl Bro Quaternary ammonium compounds such as Bevonium mide, Codeine N-Oxide, Codeine Phosphate, Codeine 10 Methyl Sulfate, Flutropium Bromide, pratropium Bro Sulfate, Cyclexanone, Dextromethorphan, Dibunate mide and Oxitropium Bromide: Sodium, Dihydrocodeine, Dihydrocodeinone Enol Xanthine derivatives such as Acefylline, Acefylline Pipera Acetate, Dimemorfan, Dimethoxanate, O.C.-Diphenyl-2- zine, Ambuphylline, Aminophylline, Bamifylline, Cho piperidinepropanol, Dropropizine, Drotebanol, Eprazi line Theophyllinate, Doxofylline, Dyphylline, Enprofyl none. Ethyl Dibunate, Ethylmorphine, Fominoben, Gua 15 line, Etamiphyllin, Eto?ylline, Guaithylline, iapate. Hydrocodone, Isoaminile, Levopropoxyphene, Proxyphylline. Theobromine, 1-Theobromineacetic Acid Morclofone, Narceline, Normethadone, Noscapine, and Theophylline; and Oxeladin, Oxolamine, Pholcodine, Picoperine, others such as Fenspinide, Medibazine, Methoxyphenanime Pipazethate, Piperidione, Prenoxdiazine Hydrochloride, and Tretoquinol. Racemethorphan, Taziprinone Hydrochloride, Tipepidine 78) Calcium channel blockers, including: and Zipeprol. Arylalkylamines such as Bepridil, Diltiazem, Fendiline, 71) Antiulcerative drugs such as Aceglutamide Aluminum Gallopanil, Prenylamine, Terodiline and Verapamil: Complex, e-Acetamidocaproic Acid Zinc salt, Acetoxolo Dihydropyridine derivatives such as Felodipine, Isradipine, nei, Arbaprostil, Benexate Hydrochloride, Bismuth Sub Nicardipine, Nifedipine, Nilvadipine, Nimodipine, Nisol citrate Sol (Dried), Carbenoxolone, Cetraxate, Cimeti 25 dipine and Nitrendipine: dine, Enprostil, Esaprazole. Famotidine, Ftaxilide, piperazine derivatives such as Cinnarizine, Flunarizine and Gefarnate, Guaiazulene, Irsogladine, Misoprostol, Niza Lidoflazine; and tidine, Omeprazole, Omoprostil, Y-Oryzanol, Pifamine, others such as Bencyclane. Etafenone and Perhexiline. Pirdenzepine, Plaunotol, Ranitidine, Rioprostil, 79) Calcium regulators such as Calcifediol, Calcitonin, Rosaprostol, Rotraxate, Roxatidine Acetate, Sofalcone, 30 Calcitriol Clodronic Acid, Dihydrotachysterol, Elcatonin, Spizofurone, Sucralfate, Teprenone, Trimoprostil, Etidronic Acid, Ipriflavone, Pamidronic Acid, Parathyroid Trithiozine, Troxipide and Zolimidine. Hormone and Teriparatide Acetate. 72) Antiurolithic drugs such as Acetohydroxamic Acid, 80) Cardlotonics such as Acefylline, Acetyldigititoxins, Allopurinol, Potassium Citrate and Succinimide. 2-Amino-4-picoline, Amrinone, Benfurodil Hemisucci 73) Antivenin drugs such as Lyovac(R) Antivenin. 35 nate, Bucladesine. Cerberoside, Camphotamide, Conval 74) Antiviral drugs, Including: latoxin, Cymarin, Denopamine. Deslanoside, Digitalin, Purines and pydrimidinones such as Acyclovir, Cytarabine, Digitalis, Digitoxin, Digoxin Dobutamine, Dopamine Dideoxyadenosine, Dideoxycytidine, Dideoxyinosine, Dopexamine, Enoximone, Erythrophleine: Fenalcomine Edoxudine, Floxuridine, Ganciclovir, Idoxuridine Inosine Gitalin, Gitoxin Glycocyamine, Heptaminol, Hydrasti Pranobex, MADU, Trifluridine Vidarabine and Zidovu 40 nine Ibopamine, Lanatosides Metamivam, Milrinone dine; and Neriifolin, Oleandrin, Ouabain, Oxyfedrine, Prenalterol, others such as Acetylleucine Monoethanolamine, Amanta Proscillaridin, Resibufogenin, Scillaren, Scillarenin, Stro dine, Amidinomycin, Cuminaldehyde Thiosemicarba phanthin, Sulmazole. Theobromine and Xamoterol. Zone, Foscarnet Sodium, Interferon-C. Interferon-B, Inter 81) Chelating agents such as Deferoxamine, Ditiocarb feron-Y, Kethoxal, Lysozyme. Methisazone, Moroxydine, 45 Sodium Edetate Calcium bisodiuml Edetate Disodium, Podophyllotoxin, Ribavirin, Rimantadine, Stallimycin, Edetate Sodium, Edetate Trisodium, Penicillamine, Pen tetate Calcium Trisodium, Pentetic Acid, Succimer and Statolon, Tromantadine and Xenazoic Acid. Trientine. 75) Anxiolytic drugs, including: 82) Cholecystokinin antagonists such as Proglumide. Arylpiperazines such as Buspirone, Gepirone and Ipsa 50 83) Cholelitholytic agents such as Chenodiol, Methyl tert pirone; Butyl Ether, Monooctanoin and Ursodiol. Benzodiazepine derivatives such as Alprazolam, Bro 84) Choleretics such as Alibendol) Anethole Trithion, AZin mazepam, Camazepam, Chlordiazepoxide, Clobazam, tamide Cholic Acid, Cicrotoic Acid, Clanobutin, Cyclobu CloraZepate, Clotiazepam, Cloxazolam, Diazepam, Ethyl tyrol, Cyclovalone, Cynarin(e), Dehydrocholic Acid, Lofiazepate, Etizolam, Fludiazepam, Flutazolam, Fluto 55 Deoxycholic Acid, Dimecrotic Acid, C. -Ethylbenzyl prazepam, Halazepam, Ketazolam, Lorazepam, Loxap Alcohol, Exiproben, Feguprol, Fencibutirol, Fenipentol ine, Medazepam, Metaclazepam, Mexazolam, Nor Florantyrone, Hymecromone, Menbutone, 3-(o-Methox dazepam, Oxazepam, Oxazolam, Pinazepam, Prazepram yphenyl)-2-phenylacrylic Acids Metochalcone and Tofisopam; Moquizone, Osalimid, Ox Bile Extract, 4,4'-Oxydi-2- Carbamates such as Cyclarbamate, Emylcamate, Hydrox 60 butanol, Piprozolin, Prozapine, 4-Salicyloylmorpholine, yphenamate, Meprobamate, Phenprobamate and Tybam Sincalide, Taurocholic Acid, Timonacic, Tocamphyl, ate, and Trepibutone and Vanitiolide. others such as Alpidem, Benzoctamine, Captodiamine, 85) Cholinergic agents such as Aceclidine, Acetylcholine Chlormezanone, Etifoxine, Fluoresone, Glutamic Acid, Bromide, Acetylcholine Chloride, Aclatonium Napadisi Hydroxyzine, Mecloralurea, Mephenoxalone, Oxana 65 late, BenZpyrinium Bromide, Bethanechol, Chloride, Car mide, Phenaglycodol, Suriclone. bachol, Carpronium Chloride, Demecarium Bromide, 76) Benzodiazepine Antagonists such as Flumazenil. Dexpantherol, Diisopropyl Paraoxon Echothiophate US 7,026,360 B1 21 22 Iodide. Edrophomium Chloride, Eseridine, Furtretho 96) Enzyme Inducers (hepatic) such as Flumecinol. nium, lsoflurcphate, Methacholine, Chloride, Muscarine, 97) Estrogens, Including: NeoStigmine, Oxapropanium, Iodide, Physostigmine and Nonsteroidal estrogens such as Benzestrol, Broparoestrol, Pyridostigmine Bromide. Chlorotrianisene, Dienestrol, Diethylstilbestrol, Diethyl 86) Cholinesterase inhibitors such as Ambenonium Chlo stilbestrol Dipropibnate, Dimestrol, Fosfestrol, Hexestrol, ride, Distigmine Bromide and Gaclanthamine. Methallenestril and Methestrol; and 87) Cholinesterase reactivators such as Obidoxime Chloride Steroidal estrogens such as Colpormon, Conjugated Estro and Pralidoxime Chloride. genic Hormones, Equilenin, Equilin, Estradiol Estradiol 88) Central nervous system stimulants and agents such as Benzoate, Estradiol 17 B-Cypionate, Estriol, Estrone, Amineptine, Amphetamine Amphetaminil, Bemegride, 10 Ethinyl Estradiol, Mestranol, Moxestrol, Mytatrienediol, Benzphetamine, Brucine, Caffeine, Chlorphentermine, Quinestradiol and Quinestrol. Clofenciclan, Clortermine, Coca, Demanyl Phosphate, 98). Gastric secretion inhibitbrs-such as Enterogastrone and Dexoxadrol, Dextroamphetamine Sulfate Diethylpropion, Octreotide. N-Ethytlamphetamine, Ethamivan, Etifelmin, 99) Glucocorticoids such as 21-Acetoxypregnenolone, Etryptamine, Fencamfamine, Fenethylline, Fenozolone, 15 AlclometaSone, Algestone, Amcinonide, Beclometha Flurothyl, Hexacyclonate Sodium, Homocamfin, Mazin Sone, Betamethasone, Budesonide, Chloroprednisone, dol, Mefexamide, Metharphetamine, Methylphenidate, Clobetasol, Clobetasone, Clocortolone, Cloprednol, Cor Nikethamide, Pemoline, Pentylenetetrazole, Phendime ticosterone, Cortisone, Cortivazoli, Deflazacort, Des trazine, Phenmetrazine, Phentermine, Picrotoxin, onide, DeSoximetasone, Dexamethasone, Diflorasone, Pipradrol, Prolintane and Pyrovalerone. Diflucortolone. Difluprednate, Enoxolone, Fluazacort, 89) Decongestants such as Amidephrine, Cafaminol, Cyclo Flucloronide, Flumethasone, Flunisolide, Fluocinolone pentamine, Ephedrine, Epinephrine, Fenoxazoline, Acetonide, Fluocinonide, Fluocortin Butyl, Fluocor Indanazoline, Metizoline, Naphazoline, Nordefrin Hydro tolone, Fluorometholone, Fluperolone, Acetate, Flupred chloride, Octodrine, Oxymetazoline, Phenylephrine nidene Acetate, Fluprednisolone, Flurandrenolide. For Hydrochloride, Phenylpropanolamine Hydrochloride, 25 mocortal, Halcinonide, Halometasone, Halopredone Phenylpropylmethylamine, Propylhexedrine, Pseu Acetate, Hydrocortamate, Hydrocortisone, Hydrocorti doephedrine, Tetrahydrozoline, Tymazoline and Xylom some Acetate, Hydrocortisone Phosphate, Hydrocortisone etazoline. 21-Sodium Succinate, Hydrocortisone Tebutate, 90) Dental caries prophylaxis such as Sodium Fluoride. Mazipredone, Medrysone, Meprednisone, Methylpred 91) Depigmentors such as Hydroquinine, Hydroquinone and 30 nisolone, Mometasone Furoate, Paramethasone, Predni Monobenzone. carbate, Prednisolone, Prednisolone 21-Diethylaminoac 92) Diuretics, including: etate, Prednisone Sodium Phosphate, Prednisolone, Organomercurials such as Chlormerodrin, Meraliunde, Mer Sodium Succinate, Prednisolone Sodium 21 m-Sulfoben camphamide, Mercaptomerin Sodium, Mercumallylic Zoate, Prednisolone 21-Stearoylglycolate, Prednisolone Acid, Mercumatilin Sodium, Mercurous Chloride and 35 Tebutate, Prednisolone 21-Trimethylacetate, Preidnisone, Mersalyl: Prednival, Prednylidene, Prednylidene 21-Diethylami Pteridines such as Furterene and Triamterene; noacetate, Tixocortal, Triamcinolone, Triamcinolone Purines such as Acefylline, 7-Morpholinomethyltheophyl Acetonide, Triamcinolone Benetonide and Triamcinolone line, Pamabrom, Protheobromine and Theobromine; Hexacetonide Steroids such as Canrenone, Oleandrin and Spironolactone; 40 100) Gonad-Stimulating principles such as Buserelin, Clo Sulfonamide derivatives such as Acetazolamide, Ambuside, miphene, Cyclofenil, Epimestrol, FSH, HCG and LH-RH. AZosemide, Bumetanide, Butazolamide, Chloraminophe 101) Gonadotropic hormones such as LH and PMSG. namide, Clofenamide, Clopamide, Clorexolone, Diphe 102) Growth hormone inhibitors such as Octreotide and nylmethane-4,4'-disulfonamide, Disulfamide, EthoXZola Somatostatin. mide, Furosemide, Indapamide, Mefruside, 45 103) Growth hormone releasing factors such as Semorelin. Methazolamide, Piretanide, Quinethazone, Torasemide, 104) Growth stimulants such as Somatotropin. Tripamide and Xipamide: 105) Hemolytic agents such as Phenylhydrazine and Phe Uracils such as Aminometradine and Amisometradine; nylhydrazine Hydrochloride. others such as Amanozine, Amiloride, Arbutin, Chlorazanil, 106) Heparin antagonists such as Hexadimethrine Bromide Ethacrynic Acid, Etozolin, Hydracarbazine, Isosorbide, 50 and Protamines. Mannitol, Metochalcone, Muzolimine, Perhexiline, Tic 107) Hepatoprotectants such as S-Adenosylmethionine, rynafen and Urea. Betaine, Catechin, Citiolone, Malotilate, Orazamide, 93) Dopamine receptor agonists such as Bromocriptine, Phosphorylcholine, Protoporphyrin IX, Silymarin-Group, Dopexamine, Fenoldopam, Ibopamine, Lisurde, Nax Thioctic Acid and Tiopronin. agolide and Pergolide. 55 108) mimunomodulators such as Amiprilose, Bucillamine, 94) Ectoparasiticides such as Amitraz, Benzyl Benzoate, Ditiocarb Sodium, Inosine Pranobex, Interferon-Yinter Carbaryl, Crotamiton DDT Dixanthogen Isobornyl Thio leukin-2, Lentinan, Muroctasin, Platonin, Procodazole, cyanoacetate-Technical, Lime Sulfurated Solution, Lin Tetramisole, Thymomodulin, Thymopentin and Uben dane, Malathion, Mercuric Oleate, Mesulphen and Sul imex. phur-Pharmaceutical. 60 109) Immunosuppressants such as Azathioprine, Cyclospor 95) Enzymes, including: Digestive enzymes such as C.-Amy ins and Mizoribine. lase (Swine Pancreas), Lipase, Pancrelipase, Pepsin and 110) Ion exchange resins such as Carbacrylic Resins, Rennin; Cholestyramine Resin, Colestipol, Polidexide, Resodec Mucolytic enzymes Such as Lysozyme; and Sodium Polystyrene Sulfonate Penicillin inactivating enzymes Such as Penicillinase; and 65 111) Lactation stimulating hormone such as Prolactin. Proteolytic enzymes Such as Collagenase, Chymopapain, 112) LH-RH agonists such as Buserelin, Goserelin, Leupro Chymotrypsins, Papain and Trypsin. lide, Nafarelin and Triptorelin. US 7,026,360 B1 23 24 113) Lipotropic agents such as N-Acetylmethionine, Cho 129) Prolactin inhibitors such as Metergoline. line Chloride, Choline Dehydrocholate Choline Dihydro 130) Prostaglandins and prostaglandin analogs such as gen Citrate Inositol, Lecithin and Methionine. Arbaprostil, Carboprost, Enprostil, Gemeprost, 114) Lupus erythematosus Suppressants such as Bismuth Limaprost, Misoprostol Ornoprostil, Prostacyclin, Pros Sodium Triglycollamate, Bismuth Subsaticylate, Chloro taglandin E. Prostaglandin E. Prostaglandin F.C. Rio quine and Hydroxychloroquine. prostil, Rosaprostol, Sulprostone and Trimoprostil. 115) Mineralcorticoids such as Aldosterone, Deoxycorticos 131) Protease Inhibitors such as Aprotinin, Camostat, terone, Deoxycorticosterone Acetate and Fludrocortisone. Gabexate and Nafamo.stat. 116) Miotic drugs such as Carbachol, Physostigmine, Pilo 132) Respiratory stimulants such as Almitrine, Bemegride, carpine and Pilocarpus. 10 Carbon Dioxides, Cropropamide, Crotethamide, Dime 117) Monoamine oxidase inhibitors such as Deprenyl, pro fline, Dimorpholamine, Doxapram, Ethamivam, Fomi clozide, Iproniazid, Isocarboxazid, Moclobemide, Octa noben, Lobeline, Mepixanox, Metamivam, Nikethamide, moxin, Pargyline Pheneizine, Phenoxypropazine, Pivalyl Picrotoxin, Pimeclone, Pyridofylline, Sodium Succinate benzhydrazine, Prodipine, Toloxatone and and Tacrine. Tranylcypromine. 15 133) Sclerosing agents such as Ethanolamine Ethylamine 118) Mucolytic agents such as Acetylcysteine Bromhexine 2-Hexyldecanoic Acid, Polidocanol, Quinine Bisulfate, Carbocysteine, Domiodol, Letosteine, Lysozyme, Mecys Quinine Urea Hydrochloride, Sodium Ricinoleate, teine Hydrochloride, Mesna, Sobrerol, Stepronin, Tiopro Sodium Tetradecyl Sulfate and Tribenroside. nin and Tyloxapol. 134) Sedatives and hypnotics, including: 119) Muscle relaxants (skeletal) such as Afloqualone, Alcu Acyclic ureides such as Acecarbromal, Apronalide, Bomi ronium, Atracurium Besylate, Baclofen, BenZoctamine, sovalum, Capuride, Carbrormal and Ectylurea; Benzoquinonium Chloride, C-Calebassine, Carisoprodol Alcohols such as Chlorhexadol, Ethchlorvynol, Meparfynol, Chlormezanone Chlorphenesin Carbamate, Chlorproet 4-Methyl-5-thiazoleethanol, tert-Pentyl Alcohol and 2.2, 2-Trichloroethanol: hazine, ChlorZoxazone, Curare, Cyclarbamate. Cycloben 25 Zaprine, Dantrolene, Decamethonium Bromide, Diaz Amides such as Butoctamide, Diethylbromoacetamide, epam, Eperisone, Fazadinium Bromide, Flumetramide, Ibrotamide, Isovaleryl Diethylamide, Niaprazine, Triceta Gallamine Triethiodide, Hexacarbacholine Bromide, mide, Trimetozine, Zolpidem and Zopiclone; Hexafluorenium Bromide, Idrocilamide, Laudexium Barbituric acid derivatives such as Allobarbital, Amobar Methyl Sulfate, Leptodactyline, Memantine, Mephenesin, 30 bital, Aprobarbital, Barbital, Bralobarbital, Butabarbital Mephenoxalone, Metaxalone, Methocarbamol, Metocu Sodium, Butalbitalf. Butallylonal, Butethal, Carbubarb, rine Iodide, Nimetazepam, Orphenadrine, Pancuronium Cyclobarbital, Cyclopentobarbital, Enallylpropymal, Bromide, Phenprobamate, Phenyramidol, Pipecurium 5-Ehtyl-5-(1-piperidyl) barbituric Acid, 5-Furfuryl-5-iso Bromide, Promoxolane, Quinine Sulfate, Styramate. Suc propylbarbituric Acid, Heptabarbital, Hexethal Sodium, cinylcholine Bromide, Succinylcholine Chloride. Succi Hexobarbital, Mephobarbital, Methitural, Narcobarbital, nylcholine Iodine, Suxethonium Bromide, Tetrazepam 35 Nealbarbital, Pentobarbital Sodium, Phenallymal, Phe Thiocolchicoside, Tizanidine, Tolperisone Tubocurarine nobarbital, Phenobarbital Sodium, Phenylmethylbarbitu Chloride Vecuronium Bromide and Zoxazolamine. ric Acid, Probarbital, Propallylonal, Proxibarbal, Reposal, 120) Narcotic antagonists Such as Amiphenazole, Cyclazo Secobarbital Sodium, Talbutal, Tetrabarbital, Vinbarbtal cine, Levallorphan, Nadide, Nalmefenef Nalorphine, Sodium and Vinylbital; 40 Benzodiazepine derivatives such as Brotizolam, Dox Nalorphine Dinicotinate, Naloxone and Naltrexone. efazepam, Estazolam, Flunitrazepam, Flurazepam, 121) Neuroprotective agents such as Dizocilpine. Haloxazolam, Loprazolam, Lorimetazepam, Nitrazepam, 122) Nootropic agents such as Aceglutamide, Acetylcar Quazepam, Temazepam and Triazolam; nitine, Aniracetam, Bifemelane. Exifone, Fipexide, Ide Bromides such as Ammonium, Bromide, Calcium Bromide behone, Indeloxazine Hydrochloride Nizofenone, Oxirac 45 Calcium Bromolactobionate, Lithium Bromide, Magne etam, Piracetam, Propentofylline, Pyritinol and Tacrine. sium Bromide, Potassium Bromide and Sodium Bromide; 123) Ophthalmic agents such as 15-ketoprostaglandins. Carbamates such as Amyl Carbamate-Tertiary, Ethinamate, 124) Ovarian hormone such as Relaxin. Hexapropymate, Meparfynol Carbamate, Novonal and 125). Oxytocic drugs such as Carboprost, Cargutocin, 50 Trichlorourethan; Deaminooxytocin, Ergonovine, Gemeprost, Methyler Chloral derivatives such as Carbocloral, Chloral Betaine, gonovine, Oxytocin, Pituitary (Posterior), Prostaglandin Chloral Formamides, Chloral Hydrate, Chloralatipyrine, E. Prostaglandin F.C. and Sparteine. Dichoralphenazone, Pentaerythritol Chloral and Triclo 126) Pepsin inhibitors such as Sodium Amylosulfate. fos; 127) Peristaltic stimulants such as Cisapride: 55 Pipendinediones such as Glutethimide: Methyprylon, Pip 128) Progestogens Such as Allylestrenol, Anagestone, Chlo eridione, Pyrithyldione, Taglutimide and Thalidomide: rmadinone Acetate, Delmadinone Acetate, Demegestone, Quinazolone derivatives Such as Etaqualone, Mecloqualone Desogestrel, Dimethisterone, Dydrogesterone, Ethister and Methaqualone; and one, Ethynodiol, Flurogestone Acetate, Gestodene, Gesto others such as Acetal, Acetophenone, Aldol, Ammonium norone Caproate, Haloprogesterone 17-Hydroxy-16-me 60 Valerate, Amphenidone, d-Bornyl C-Bromoisovalerate, thylene-progesterone, 17-Hydroxyprogesterone, 17C.- d-Bornyl Isovalerate, Bromoform, Calcium 2-Ethylbu Hydroxyprogesterone Caproate, Lynestrenol, tanoate, Carfinate, C.-Chloralose Clomethiazole, Cypripe Medrogestone, Medroxyprogesterone, Megestrol Acetate, dium, Doxylamine, Etodroxizine, Etomidate, Fenadiaz Melengestrol, Norethindrone, Norethynodrel, Norgester ole, Homofenazine, Hydrobromic Acid, Mecloxamine, one, Norgestimate, Norgestrel, Norgestrienone, Norvinis 65 Menthyl Valerate, Opium, Paraldehyde, Perlapine, Propi terone, Pentagestrone, Progesterone, Promegestone, omazine, Rilmazafone Sodium Oxybate, Sulfonethyl Quingestrone and Trengestone. methane and Sulfonmethane. US 7,026,360 B1 25 26 135) Thrombolytic agents such as APSAC, Plasmin, Pro Urokinase, Streptokinase, Tissue Plasminogen Activator and Urokinase. 136) Thyrotropic hormones such as TRH and TSH. 137) Uricosurics such as Benzbromarone, Ethebenecidc, Orotic Acid, Oxycinchophen, Probenecid, Sulfinpyra Zone, Ticrynafen and Zoxazolamine. with UV activated oxygen. 138) Vasodilators (cerebral) such as Bencyclane, Cinnariz 10 The invention claimed is: ine, Citicoline, Cyclandelate, Ciclonicate, Diisopropy 1. A pharmaceutical composition comprising, in addition lamine Dichloroacetate, Eburnamonine, Fenoxedil, Flu to one or more pharmacologically active ingredient, wherein narizine, Ibudilast, Ifenprodil, Nafronyl, Nicametate, the active ingredient is Troxerutine, Nimesulide, or a non Nicergoline, Nimodipine, Papaverine, Pentifylline, steroidal anti-inflammatory drug, wherein said non-steroidal Tinofedrine, Vincamine, Vinpocetine and Vicquidil. 15 anti-inflammatory drug is Ketoprofen, Diclofenac Sodium, 139) Vasodilators (coronary) such as Amotriphene, Benda Ibuprofen, Etodolic Acid, Piroxicam, or a combination Zol, Benfurodil Hemisuccinate, BenZiodarone, Chlo thereof, racizine, Chromonar Clobenfurol, Clonitrate, Dilazep, between 0.01 percent and 60 percent by weight of a Dipyridamole, Droprenilamine, Efloxate, Erythritol, compound of formula I Erythrity1 Tetranitrate, Etafenone, Fendiline, Floredil, Ganglefene), Hexestrol Bis(B-diethylaminoethyl ether), Hexobendine, Itramin Tosylate, Khellin, Lidoflazine, Mannitol Hexanitrate, Medibazine Nicorandil, Nitroglyc CF erin, Pentaerythritol Tetranitrate, Pentrinitrol, Perhexiline, 25 Pimethylline, Prenylamine, Propatyl Nitrate, Pyrdo?yl line, Trapidil, Tricromyl, Trimetazidine, Trolnitrate Phos with n and mid 18 and <46 and with a molecular weight phate and Visnadine. between about 600 and about 18,000, in combination with 140) Vasodilators (peripheral) such as Aluminum Nicoti 0.01% to 20% by weight of phosphatidylcholine, for nate, Bamethan Bencyclane, Betahistine, Bradykinin, 30 enhancement of active-ingredient absorption. Brovincamined, Bufoniode, Buflomedil Butalamine, 2. A pharmaceutical composition according to claim 1 Cetiedit, Cicionicate, Cinepazide, Cinnarizine, Cyclande with 0.1 percent to 30 per cent by weight of the compound late, Diisopropylamine Dichloracetate, Eledoisin, of formula I with n and mid-24 and <36 and with the Fenoxedil, Flunarizine, Hepronicate, Ifenprodil, Inositol molecular weight between 1,000 and 4,000. 35 3. A pharmaceutical composition according to claim 1, Niacinate, Isoxsuprine, Kallidin, Kallikrein, Moxisylyte, wherein the composition is in a form selected from the group Nafronyt1, Nicametate, Nicergoline, Nicofuranose, Nic consisting of creams, emulsions, ointments, lotions, foams, otinyl Alcohol, Nylidein, Pentifylline, Pentoxifylline, Pir gels, aspersion powders, and transdermal formulations. ibedil, Prostaglandin E. Suloctidil and Xanthinol Niaci 4. A method for enhancing absorption of a pharmacologi nate. 40 cally active ingredient, wherein the method comprises topi 141) Vasoprotectants such as Benzarone, Bioflavonoids, cally applying the pharmaceutical composition claimed in Chromocarb, Clobenoside, Diosmin, Dobesilate Calcium, claim 1 to a patient in need thereof wherein the active Escin, Folescutol, Leucocvanidin, Metescufylline, Quer ingredient is absorbed through derma, cutis, mucosa, rec cetin, Rutin and Troxerutin. tum, vagina, or urethra. 142) Vitamins, vitamin Sources and vitamin extracts such as 45 5. A pharmaceutical composition according to claim 2, Vitamins A, B, C, D, E and K and derivatives thereof, wherein the composition is in a form selected from the group Calciferols, Glycyrrhiza, and Mecobalamin. consisting of creams, emulsions, ointments, lotions, foams, 143) Vulnerary agents such as Acetylcysteine, Allantoin, gels, aspersion powders, and transdermal formulations. Asiaticoside, Cadexomer Iodine, Chitin, Dextranomer 6. The composition according to claim 1, wherein trans and Oxaceprol. 50 absorption of the active ingredient is increased by up to more than five times its normal value. The use referred to herein increases percutaneous absorp 7. The composition according to claim 2, wherein trans tion of drugs by over 5 times their normal capacity. absorption of the active ingredient is increased by up to more Finally, the invention also regards the compounds belong than five times its normal value. ing to the Perfluoropolyester class of formula I 55 8. A method for enhancing absorption of a pharmacologi cally active ingredient, wherein the method comprises topi cally applying the pharmaceutical composition claimed in claim 2 to a patient in need thereof, wherein the active 60 ingredient is absorbed through derma, cutis, mucosa, rec CF tum, vagina, or urethra. 9. A pharmaceutical composition as claimed in claim 1, wherein trans-absorption of the active ingredient is with n and mid 18 and <46 and with molecular weights increased by up to more than ten times its normal value. between -600 and ~8000, especially those with n and ma24 65 10. A pharmaceutical composition as claimed in claim 1, and <36 with molecular weights between 1000 and 4000, wherein trans-absorption of the active ingredient is obtained by polymerization of hexafluoropropene increased by up to more than 20 times its normal value. US 7,026,360 B1 27 28 11. A method as claimed in claim 4, wherein trans (6) optionally methyl-p-hydroxybenzoate; absorption of the active ingredient is increased by up to more (7) optionally propyl-p-hydroxybenzoate; than ten times its normal value. (8) optionally phenoxyethanol: 12. A method as claimed in claim 4, wherein trans (9) optionally nor-chenodeoxycolic acid; absorption of the active ingredient is increased by up to more (10) optionally transcutol; than 20 times its normal value. (11) optionally lactic acid; 13. A pharmaceutical composition as claimed in claim 1, (12) optionally ethyl alcohol; and wherein the active ingredient is troXerutine. (13) optionally water. 14. A method as claimed in claim 4, wherein the active 17. A pharmaceutical composition as claimed in claim 15, ingredient is troXerutine. 10 wherein the active ingredient is troXerutine. 15. A pharmaceutical composition consisting essentially 18. A pharmaceutical composition according to claim 15, of wherein the phosphatidlycholine constitutes 0.01 percent to (1) one or more pharmacologically active ingredient, 10 percent by weight of the pharmaceutical composition, wherein the active ingredient is Troxerutine, Nime and wherein the compound of the formula I has a molecular Sulide, or a nonsteroidal anti-inflammatory drug, 15 weight between 1,000 and about 4,000 with n and m each wherein said non-steroidal anti-inflammatory drug is greater than 24 and each less than 36. Ketoprofen, Diclofenac Sodium, Ibuprofen, Etodolic 19. A pharmaceutical composition according to claim 17. Acid, Piroxicam, or a combination thereof; wherein the phosphatidlycholine constitutes 0.01 per cent to (2) between about 0.01 percent and about 60 percent by 10 percent by weight of the pharmaceutical composition, weight of a compound of formula I and wherein the compound of the formula I has a molecular weight between 1,000 and about 4,000 with n and m each greater than 24 and each less than 36. 20. A pharmaceutical composition as claimed in claim 16, wherein the active ingredient is troXerutine. CF 25 21. A pharmaceutical composition according to claim 16, wherein the phosphatidlycholine constitutes 0.01 percent to 10 percent by weight of the pharmaceutical composition, wherein in and m are each greater than 18 and are each less and wherein the compound of the formula I has a molecular than 46 and wherein the compound of the formula I has a weight between 1,000 and about 4,000 with n and m each molecular weight between about 600 and about 8,000; 30 greater than 24 and each less than 36. (3) phosphatidylcholine; 22. A pharmaceutical composition according to claim 20, (4) optionally tocopherol acetate; wherein the phosphatidlycholine constitutes 0.01 percent to (5) optionally polyacrylamide, C-C isoparaffin, and 10 percent by weight of the pharmaceutical composition, laureth-7; and wherein the compound of the formula I has a molecular (6) optionally methyl-p-hydroxybenzoate: 35 weight between 1,000 and about 4,000 with n and m each (7) optionally propyl-p-hydroxybenzoate; greater than 24 and each less than 36. (8) optionally phenoxyethanol: 23. The method according to claim 4, wherein the active (9) optionally nor-chenodeoxycolic acid; ingredient is Troxerutine, Nimesulide, Ketopropfen, (10) optionally transcutol; and Etodolic Acid, or a combination thereof. (11) optionally water. 40 24. The pharmaceutical composition as claimed in claim 16. A pharmaceutical composition consisting essentially 15, wherein the active ingredient is Troxerutine, Nimesulide, of: Ketopropfen, Etodolic Acid, or a combination thereof. (1) one or more pharmacologically active ingredient, 25. The pharmaceutical composition as claimed in claim wherein the active ingredient is Troxerutine, Nime 15, wherein the active ingredient is Troxerutine, Nimesulide, Sulide, or a non steroidal anti-inflammatory drug, 45 Ketopropfen, Etodolic Acid, or a combination thereof. wherein said non-steroidal anti-inflammatory drug is 26. The pharmaceutical composition as claimed in claim Ketoprofen, Diclofenac Sodium, Ibuprofen, Etodolic 16, wherein the active ingredient is Troxerutine, Nimesulide, Acid, Piroxicam, or a combination thereof; Ketopropfen, Etodolic Acid, or a combination thereof. (2) between about 0.01 percent and about 60 percent by 27. The pharmaceutical composition as claimed in claim weight of a compound of formula I 50 1, wherein phosphatidylcholine is 0.01% to 10% by weight of the pharmaceutical composition. 28. The pharmaceutical composition as claimed in claim 15, wherein the composition consists essentially of the one or more active ingredient, wherein the active ingredient is 55 Troxerutine, Nimesulide, or a non-steroidal anti-inflamma CF tory drug, wherein said nonsteroidal anti-inflammatory drug is Ketoprofen, Diclofenac Sodium, Ibuprofen, Etodolic wherein in and m are each greater than 18 and are each less Acid, Piroxicam, or a combination thereof, the compound than 46 and wherein the compound of the formula I has a formula I, the phosphatidylcholine, and optionally the water. molecular weight between about 600 and about 8,000; 60 29. A method according to claim 4, wherein trans-absorp (3) phosphatidylcholine; tion of the active ingredient is increased by up to more than (4) optionally tocopherol acetate; five times its normal value. (5) optionally polyacrylamide, C-C isoparaffin, and laureth-7;