Abstract:
A pharmaceutical composition contains chlorhexidine and glutaraldehyde in a pharmaceutically acceptable carrier; in the form of a mouthwash, the composition is effective in controlling fungal or yeast infections in the oral cavity, such as associated with subjects suffering from AIDS, cancer and periodontal diseases; in particular the composition is effective against fungi of the genus Candida including Candida albicans and Candida krusei.

Description:
BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     This invention relates to a pharmaceutical composition and a method of treatment; more especially the invention is concerned with such a composition in the form of a mouthwash for treatment of fungal or yeast infections in the oral cavity; and with a method of treating subjects with fungal or yeast infections. 
     2. Description of Prior Art 
     Fungal or yeast infections in the mouth and throat are exhibited by patients suffering from AIDS, cancer and periodontal disorders. 
     There is no satisfactory treatment for these infections. 
     Chlorhexidine or N,N&#39;-bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradecanediimidamide is a known disinfectant and topical antibacterial. 
     Glutaraldehyde or 1,3-diformylpropane is a known disinfectant used in high level disinfection of surgical equipment including equipment which can not be heat sterilized. 
     SUMMARY OF THE INVENTION 
     It is an object of this invention to provide a pharmaceutical composition, more especially a composition in the form of a mouthwash. 
     It is a further object of this invention to provide such a composition for treatment of Candida infections, especially in subjects having AIDS, cancer or periodontal diseases. 
     It is a further object of this invention to provide a method of treating subjects having fungal or yeast infections. 
     It has now been found that a pharmaceutical composition based on chlorhexidine and glutaraldehyde is effective in controlling such fungal and yeast infections and provides superior results when compared with prior compositions. 
     In accordance with the invention there is provide a pharmaceutical composition comprising a pharmacologically effective, pharmacologically acceptable amount of chlorhexidine and a pharmacologically effective, pharmacologically acceptable amount of glutaraldehyde, in association with a pharmaceutically acceptable carrier. 
     In another aspect of the invention there is provided a method of treating subjects having fungal or yeast infections which comprises application to the site of the infection, of a composition of the invention. 
     In accordance with still another aspect of the invention there is provided use of a composition of the invention in the treatment of subjects having AIDS, cancer or periodontal diseases. 
    
    
     DESCRIPTION OF PREFERRED EMBODIMENTS 
     The composition of the invention is, in particular, an antifungal or antiyeast infection composition. 
     The composition of the invention is especially useful as a mouthwash, in which the pharmaceutically acceptable carrier is water. 
     Employed as a mouthwash the composition may suitably contain about 0.2%, by volume, of the chlorhexidine and about 0.004%, by volume, of the glutaraldehyde. 
     In general the composition should not contain more than 0.5%, by volume, of the chlorhexidine; and not more than about 0.01%, by volume, of gluteraldehyde. 
     The composition may also suitably contain a lower alcohol of 1 to 4 carbon atoms, especially ethyl alcohol, which has antiseptic activity. The alcohol may be present in an amount of about 7%, by volume. 
     In order to render the composition more palatable as a mouthwash it may suitably include a flavouring agent and a colourant, in a flavouring or colouring amount, respectively. Suitable flavouring agents include anise oil and peppermint oil, each of which may be present in an amount of about 0.06%, by volume; suitable colourants include Red Dye No. 7 which may be employed in an amount of about 0.001%, by volume. 
     In the case in which anise oil or peppermint oil are included in the composition it is appropriate to include a dispersing, suspending or emulsifying agent to disperse, suspend or emulsify the oils in the aqueous medium; one suitable agent is a derivative of castor oil and ethylene oxide also described as a polyethylene glycol glycerol hydrogenated castor oil available from BASF under the Trade Mark Cremophor; this agent may be used in an amount of about 0.8%, by volume. 
     The composition of the invention in the form of a mouthwash is found to be effective in controlling fungus or yeast infections of the genus Candida, for example, Candida albicans and Candida krusei. These infections are experienced by persons suffering from AIDS and cancer and also by persons suffering from periodontal diseases. The composition does not provide a cure for the infection, but the infection may be controlled by periodic use of the composition. Typically the mouthwash may be applied by gargling or rinsing the mouth with the mouthwash 2-3 times. Surprisingly, the mouthwash is found to be non-toxic to mucous tissue in the oral cavity. 
     Chlorhexidine and glutaraldehyde are both soluble in water, and can be readily dissolved in an aqueous pharmaceutically acceptable carrier. However, when flavouring oils, such as anise oil and peppermint oil are employed, the oils are first mixed with the alcohol and the suspending agent. Separately the chlorhexidine and the glutaraldehyde are mixed with a first portion of the water to form a solution; and the colourant is mixed with a second portion of the water. 
     The mix of oils and alcohol is admixed with the aqueous solution of chlorhexidine and glutaraldehyde until a homogeneous suspension is obtained; thereafter the aqueous solution of the colourant is admixed with the suspension, and the resulting suspension is filtered. 
     It will be understood that the % amounts indicated herein for individual ingredients are in wt. % Furthermore, these amounts are not intended to be restrictive, but are merely illustrative of useful amounts. It is well within the skill of persons in the art to determine useful variations in the amounts by routine experiments. 
     In comparison studies a composition of the invention was compared with Virkon, an oxidizing disinfectant based on potassium monoperoxysulphate manufactured by Antec International Ltd. of Suffolk, England; the composition of the invention was of the following formulation: 
     
         ______________________________________Chlorhexidine        50 ml (1%) = 0.2% (20% solution)Glutaraldehyde        2 ml (0.2%) = 0.004% (2% solution)Cremophor    8 g (0.8%)Red Dye No. 7        0.01 mg (0.001%)Anise oil    0.6 ml (0.06%)Peppermint oil        0.6 ml (0.06%)Alcohol 95%  70 ml (7%)Water        1000 ml______________________________________ 
    
     Both compositions were found to be effective in killing Candida albicans within seconds. In the case of Candida krusei it took 20 minutes for the Virkon to destroy the yeast, which is clearly too long an exposure time for a mouthwash; on the other hand, the composition of the invention killed the strain instantly by cell lysis.