CA2416512A1

CA2416512A1 - Enhancement of the action of anti-infective agents

Info

Publication number: CA2416512A1
Application number: CA002416512A
Authority: CA
Inventors: Petrus Johannes Meyer
Original assignee: Pitmy International N.V.; Petrus Johannes Meyer; North West University
Current assignee: North West University
Priority date: 2000-07-19
Filing date: 2001-07-19
Publication date: 2002-01-24
Anticipated expiration: 2021-07-19
Also published as: WO2002005850A3; CA2416512C; CN1458847A; AU2001283586A1; WO2002005850A2; CN100531799C

Abstract

The invention provides a method of enhancing the action of a pharmaceutical agent selected from the group consisting of the group comprising antimicrobi al agents, the anthelmintic agents and the anti-ectoparasitic agents, but excluding coal tar solution and H1-antagonist antihistamines, characterised in that the agent is formulated with an administration medium which comprises a solution of nitrous oxide gas in a pharmaceutically acceptable carrier solve nt for the gas and which administration medium includes at least one fatty acid or ester or other suitable derivative thereof selected from the group consisting of oleic acid, linoleic acid, alpha-linolenic acid, gamma-linolen ic acid, arachidonic acid, eicosapentaenoic acid [C20: 5.omega.3], decosahexaenoic acid [C22: 6.omega.3], ricinoleic acid and derivatives there of selected from the group consisting of the C1 to C6 alkyl esters thereof, the glycerol-polyethylene glycol esters thereof and the reaction product of hydrogenated natural oils composed largely of ricinoleic acid based oils, su ch as castor oil with ethylene oxide.

Claims

1. A method of enhancing the action of an anti-infective agent characterised in that the agent is selected from the group comprising antimicrobial agents, the anthelmintic agents and the anti-ectoparasitic agents, but excluding coal tar solution and H1-antagonist antihistamines, comprising the step of formulating the agent with an administration medium which comprises a solution of nitrous oxide gas in a pharmaceutically acceptable carrier solvent for the gas and which medium includes at least one fatty acid or ester or other suitable derivative thereof selected from the group consisting of oleic acid, linoleic acid, alpha-linolenic acid, gamma-linolenic acid, arachidonic acid, eicosapentaenoic acid [C20: 5.omega.3], decosahexaenoic acid [C22: 6.omega.3], ricinoleic acid and the derivatives thereof selected from the group consisting of the C1 to C6 alkyl esters thereof, the glycerol-polyethylene glycol esters thereof and the reaction product of hydrogenated natural oils composed largely of ricinoleic acid based oils, such as castor oil, with ethylene oxide.

2. A pharmaceutical preparation comprising an anti-infective characterised in that the agent is selected from the group comprising antimicrobial agents, the anthelmintic agents and the anti-ectoparasitic agents, but excluding coal tar solution and H1-antagonist antihistamines, which agent is formulated with an administration medium which comprises a solution of nitrous oxide gas in a pharmaceutically acceptable carrier solvent for the gas and which medium includes at least one fatty acid or ester or other suitable derivative thereof selected from the group consisting of oleic acid, linoleic acid, alpha-linolenic acid, gamma-linolenic acid, arachidonic acid, eicosapentaenoic acid [C20: 5.omega.3], decosahexaenoic acid [C22: 6.omega.3], ricinoleic acid and the derivatives thereof selected from the group consisting of the C1 to C6 alkyl esters thereof, the glycerol-polyethylene glycol esters thereof and the reaction product of hydrogenated natural oils composed largely of ricinoleic acid based oils, such as castor oil, with ethylene oxide.

3. The method of claim 1 or the preparation of claim 2 which contains a mixture of esters of the essential fatty acids set out in those claims and is preferably constituted by the complex known as Vitamin F Ethyl Ester having a typical fatty acid distribution as follows:

< C16: 0 C16.0: 8,3 %
C18.0: 3,5 %
C18.1 2.1,7 %
C18.2: 34,8 %
C18.4 28,0 %
> C18: 1,6 %
unknown: 2,1 %

4. The method or the preparation of claim 3 wherein the administration medium further includes eicosapentaenoic acid [C20:

5.omega.3] and/or decosahexaenoic acid [C22: 6.omega.3] as additional long chain fatty acids and/or the reaction product of hydrogenated castor oil and ethylene oxide known as PEG-n-Hydrogenated Castor Oil.

5. The method of claim 1 or the preparation of claim 2 wherein the carrier is water (preferably deionised water) or any of the pharmaceutically acceptable alcohols, ethers, polymers such as a polyethylene glycol or the like or an oil which is preferably an organic oil which organic oil is further preferably an essential oil based on long chain fatty acids having between 14 and 22 carbon atoms in the fatty acid and is preferably of natural origin and most preferably a plant oil rich in gamma linolenic acid [GLA].

6. The method of claim 1 or the preparation of claim 2 wherein the anti-infective agent is formulated in a liquid or encapsulated liquid presentation for oral administration or in a nasal or bronchial or pulmonary spray or in the form of an injectable formulation and wherein the formulation incorporate, as part of the administration medium, water or acceptable other liquid into which the nitrous oxide is dissolved, preferably to saturation, and wherein the fatty acid or ester thereof is either dissolved or suspended or emulsified along with the anti-infective agent.

7. The method of claim 1 or the preparation or claim 2 wherein the anti-infective agent is formulated as a topical, buccal or vaginal cream or ointment, or as a suppository, and wherein the formulation used in making up such cream, ointment or suppository incorporates, along with the anti-infective agent to be enhanced, a quantity of water or other liquid containing, and preferably saturated with, nitrous oxide, the long chain fatty acid or ester thereof and the anti-infective agent formulated therewith, and, optionally further incorporates such additional excipients and carriers as are conventionally used in the pharmaceutical trade in making up such dosage forms.

8. The method of claim 1 or the preparation of claim 2 wherein the carrier solvent for the nitrous oxide gas is essentially non-aqueous and composed of at least one fatty acid or ester thereof selected from the group consisting of oleic acid, linoleic acid, alpha-linolenic acid, gamma-linolenic acid, arachidonic acid, eicosapentaenoic acid [C20: 5.omega.3], decosahexaenoic acid [C22: 6.omega.3], ricinoleic acid and derivatives thereof selected from the group consisting of the C1 to C6 alkyl esters thereof, the glycerol-polyethylene glycol esters thereof and the reaction product of hydrogenated natural oils composed largely of ricinoleic acid based oils with ethylene oxide, required to be part of the formulation.

9. The method of claim 1 or the preparation of claim 2 wherein the anti-microbial agent is selected from the groups consisting of the anti-bacterial agents (including both antibiotics and substances other than antibiotics such as the sulfonamides, the erythromycins and other macrolides, the aminoglycocides, the tetracyclines, the chloramphenicols and the quinolones);
the anti-fungal agents;
the anti-viral agents (including anti-retroviral agents);
the anti-protozoal agents;
the tuberculostatics;
the anti-leprotics;
the germicides;
and the spirochaeticides.

10. The method of claim 1 or the preparation of claim 2 wherein the anti-infective agent is selected from the group comprising: the anthelmintics, the anti-ectoparasitcides, the anti-bacterial agents (including both antibiotics and antibacterial substances other than antibiotics); the antifungal agents; the anti-viral agents; the anti-protozoal agents; the tuberculostatics; the anti-leprotics; the germicides; and the spirochaeticides.

11. The method or the preparation of claim 9 wherein the anti-infective agent comprise at least one tuberculostatic selected from the group consisting of Rifampicin, Izoniazid, Pyrazinamide and Ethambutol.

12. The method or preparation of claim 11 wherein the anti-TB
formulation is prepared to be adapted for pulmonary administration.

13. The method or the preparation of claim 9 wherein the anti-infective agent comprise at least one of the ingredients selected from the group consisting of Acrosoxacin, Acyclovir, Amantadine, Amicacin, Amifloxacin, Amikacin, Aminosalicyclic Acid, Amoxicillin, Amphotericin B, Ampicillin, Apalcillin, Azidamphenicol, Azithromycin, Aziocillin, Aztreonam, Bacampicillin, Bacitracin, Bacitracin Zinc, Benzoic Acid and Salicyclic Acid, Benzyl penicillin (Penicillin G), Butoconazole, Capreomycin, Carbenicillin, Carfecillin, Carindacillin, Cefaclor, Cefadroxil, Cefalexin, Cefamycins, Cefdinir, Cefepime, Cefetamet PivoXil, Cefixime, Cefmenoxime, Cefodizime, Cefonicid, Cefoperazone, Ceforanide, Cefotaxime, Cefotetan, Cefotiam, Cefoxitin, Cefpiramide, Cefprozil, Cefsulodin, Ceftazidime, Ceftibuten, Ceftizoxime, Ceftriaxone, Cefuroxim, Cefuroxime Axetil, Cephaloridine, Cephamandole, Cephazolin/Cephradine, Cephradine, Cetatriazine, Chloramphenicol, Chloramphenicol, Chlortetracycline, Ciclopirox, Ciclopirox Olamine, Cinoxacin, Cipofloxacin, Ciprofloxacin, Clarithromycin, Clavulanic Acid, Clindamycin, Clofazimine; Clotrimazole, Cloxacillin, Colistin (Colisten Sulfate), Co-Trimoxazole (Trimethoprim + Sulphamethoxazole), Cycloserine, Dapsone, Demeclocycline, Dicloxacillin, Didanosine, Doxycycline, Econazole, Enoxacin, Enrofloxacin, Erythromycin, Ethambutol, Ethionamide; Famciclovir, Fleroxacin, Flucloxacillin, Fluconazole, Flucytosine, Fluxonazole, Foscarnet, Ganciclovir, Gentamicin, Gentamicin Sulfate, Glycylcylines, Griseofulvin, Haloprogin, Hetacillin, Idoxuridine, Imidazoles, Imipenem, Interferons Alfa, Intrathecal, Iodide, Isoniazid, Itraconazole, Kanamycin, Ketoconazole, Lamivudine, Latamoxef (Oxacephalosporin), Levofloxacin, Lomefloxacin, Loracarbef, Mafenide Acetate, Menazopyridine, Meropenem, Metaampicillin, Methacycline, Methenamin, Methicillin, Mezlocillin, Miconazole, Miningeal, Minocycline; Nadifloxacin, Nafcillin, Naftifine, Nalidixic Acid (Oxolinic Acid), Natamycin, Neomycin, Netilmicin, Nitrofurantoin, Norfloxacin, Nystatin, Ofloxacin, Oxacillin, Oxiconazole, Oxytetracycline, Pefloxacin, Penciclovir, Phenoxymethyl-Penicillin (Penicillin V), Phthalylsulphathiazole, Pipemidic Acid, Piperacillin, Piromidic Acid, Pivampicillin, Pivcephalexin, Pivmecillinam, Polymyxin B (Polymyxin B Sulfate), Potassium Iodide, Propionic Acid And Caprylic Acid, Pyrazinamide, Ramoplanin (Glycopeptide), Riampin, Ribavirin, Rifabutin, Rifampin, Rimantadine, Roxithromycin, Rp 59500, Rufloxacin, Silver Sulphadiazine, Sorivudine, Sparfloxacin, Spectinomycin, Stavudine, Streptomycin, Succinylsulphathiazole, Sulbactam, Sulconazole, Sulfacetamide Sodium, Sulfadoxine, Sulfametopyrazine, Sulfisoxazole Diolamine, Sulphacetamide, Sulphadiazine, Sulphadimethoxine, Sulphadimidine, Sulphafurazole, Sulphaguanidine, Sulphamethoxazole, Sulphamethoxydiazine, Sulphamethoxypyridazine, Sulphapyridine, Sulphasalazine, Talampicillin, Tazobactam, Teicoplanin (Glycopeptide), Temocillin, Terbinafine, Terconazole, Terconazole, Tetracycline, Tetracycline Hydrochloride, Thiamphenicol, Ticarcillin, Tioconazole, Tobramycin, Tobramycin Sulfate, Tolnaftate, Tosufloxacin, Trifluridine, Undecylenate, Undecylenic Acid, Valacyclovir, Vancomycin, Vidarabine, Vidarabine, Zalcitabine, Zidovudine.