Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – C-o-group doai
Reexamination Certificate
2000-09-25
2002-07-02
Weddington, Kevin E. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
C-o-group doai
Reexamination Certificate
active
06414035
ABSTRACT:
The present invention relates to the use of polyols such as xylitol for the preparation of a composition to be administered in the treatment or prophylaxis of mucosal yeast infection in mammals, as well as to preparations for use in the systemic or topical therapeutic or prophylactic treatment of mucosal yeast infections. The invention relates specifically but not solely to the combating of infections caused by Candida s.p. in mucosa in connection with exocrine glands of the mammalian body.
Despite the availability of effective antifungal drugs, optimal prophylactic and therapeutic approaches for mucositis are still controversial. Factors that might have a stimulatory effect on fungal growth or decrease the effectiveness of antifungal therapy of mucositis have received little attention.
Oral candidiasis is the most common opportunistic infection in AIDS, affecting up to 90% of the patients. It importantly interferes with nutrition. Studies suggest that the presence of oral candidiasis increases progression to AIDS, and that oral candidiasis is an independent risk factor for the development of
Pneumocystis carinii
pneumonia. Oral candidiasis is also one of the most common reasons for premature cessation of chemotherapy in cancer patients.
Optimal prophylaxis and therapy of oral candidiasis are still controversial issues. Oral nystatin and amphotericin B are usually effective, but compliance is problematic due to the unpalatable taste and gastric intolerance of these compounds. Drugs based on azoles are also effective, but resistance is an increasingly recognized problem. Recurrences are common. These issues warrant the search for novel strategies to prevent or treat candidiasis.
It is known that sucrose favours the growth of Candida in vitro and sucrose rinses have been thought to induce the development of oral candidiasis in some patients with dentures. Sucrose also increases gastrointestinal growth and mucosal invasion of
Candida albicans
in murine models.
Sucrose is the most commonly used sweetener for food and pharmaceutical contexts. Although a wide variety of alternate sweeteners are available, sucrose is generally considered to be the optimum sweetener with regard to taste profile and technological properties However, sucrose has been implicated as a contributory factor in many diseases including hypertension. coronary heart disease, arterial sclerosis and dental caries.
Perhaps the most significant, well-documented effect of sucrose is its contribution to tooth decay. The mouth contains a number of bacterial strains which ferment common dietary carbohydrates such as sucrose. This fermentation generates acid as an end product which lowers the pH in the mouth; the lowered pH leads to a demineralization of tooth enamel and finally to the formation of dental lesions of caries.
One approach to fighting dental caries is to reduce or eliminate the amount of fermentable carbohydrates such as sucrose in pharmaceutical or food contexts. The replacement of fermentable carbohydrates by sugar substitutes which cannot be fermented, or are less easily fermented by
S. mutans
and other bacteria has been shown to decrease the development of dental caries.
Xylitol is a naturally occurring five carbon sugar alcohol which has the same sweetness as sugar and a caloric content which is less than that of sugar. Xylitol is found in small amounts in many fruits and vegetables and is produced in the human body during normal metabolism. Xylitol is attractive as a sugar substitute in food contexts because of its known metabolic, dental and technical characteristics.
Xylitol has been used as a sugar substitute in certain contexts, such as chewing gum [U.S. Pat. No. 4,514,422 (Yang) and 3,422,184 (Patel)] with practical and commercial success. Xylitol has also been used in tablets [WO 92/10168 (Xyrofin Oy)], in sweets and chocolate, etc.
From a metabolic perspective, xylitol is metabolized largely independent of insulin, so it can be safely consumed by non-insulin dependent diabetics. A significant advantage of xylitol is that it is not fermented by
S. mutans
and other bacteria found in the mouth and, therefore, does not produce acids which, as described above, contribute to the formation of dental caries. Xylitol is well established as a non-cariogenic substance, i.e. xylitol does not contribute to caries formation. Significant data also exists which supports the view that xylitol is not only non-cariogenic, but actively suppresses the formation of new caries and may even reverse existing lesions by inducing remineralization, i.e. it is a cariostatic material.
A summary of clinical data regarding the effects of xylitol and its possible mechanisms is set forth in Bar, Albert,
Caries Prevention With Xylitol: A Review of a Scientific Evidence
, 55 Wld. Rev. Nutr. Diet. 183-209 (1983). The mechanism or mechanisms by which xylitol effects any cariostatic properties is not yet known, but some possible mechanisms which have been suggested include a reduction of oral levels of
S. mutans
, a reduction in the development of plaque, the stimulation of the flow of protective saliva, the favorable alteration of the composition of saliva, the retardation of demineralization and a enhancement of remineralization of tooth enamel.
Other polyols, such as sorbitol, mannitol and lactitol have also been substituted for sucrose in a variety of contexts. All of these polyols have certain advantages, such as non-cario-genicity, over sucrose. However, none of the other polyols have been demonstrated to have a cariostatic effect. Xylitol is also known to have a better patient compliance than other polyols.
In a study examining the oral microflora in relation to caries, it was found (M. Larmas, et al., Acta Odontologica Scandinavia, Vol. 33, Suppl. 70, 1975, p. 45-55) that substituting xylitol for sucrose in the diet of a human test group during 8 months significantly reduced the number of persons with salivary Candida growth, while there was a slight increase in the test groups receiving sucrose and fructose. At the base line practically every second person had Candida in the saliva.
Xylitol has been documented [S. L. Vargas et al., Infect. Immun. 1993; 61(2):619-26] as a potential candidate for replacing glucose in an immunocompromised murine model of gastrointestinal candidiasis, as it did not increase Candida growth nor invasion compared to controls when given instead of glucose. Mice receiving xylitol had five times less invasion of gastrointestinal mucosa by Candida, than did mice receiving glucose. Xylitol scores of invasion were not significantly different from those of the control mice receiving no sugar.
A two month regular use of xylitol chewing gum has been shown to reduce the occurrence of acute otitis media in children [M. Uhari, et al., BMJ, Vol. 313 (1996); 1180-1184]. The effect was attributed to the efficacy of xylitol in reducing the growth of
S. pneumoniae
and thus preventing the attacks of acute otitis media caused by pneumococci.
The occurrence of mucositis and especially oral candidiasis in AIDS patients is an increasing problem in the world. Antifungal therapies have not proven successful in all cases and fungal resistance to the available drugs is a frequent problem. Oral candidiasis is very painful and provides the patients with a poor quality of life. There is felt to be a real need for improving the available therapies for mucositis.
Despite the fact that the beneficial effect of replacing sucrose with xylitol in combating dental caries has been known for a long time and although xylitol was found not to increase gastrointestinal candidiasis as much as sucrose, no suggestion has been made for utilizing xylitol or other polyols for combating mucositis caused by yeasts on mucosa in close connection with exocrine glands of the body.
The present inventors have now surprisingly found that a polyol such as xylitol has a marked beneficial effect in preventing yeast growth on mucosa at various orifices of the body and that said polyol consequently is use
Pearson Julita
Pepper Tammy
Saunders David
Vargas Munita Sergio Luis
Virkki Markku
Scully Scott Murphy & Presser
Weddington Kevin E.
Xyrofin Oy
LandOfFree
Use of polyols in combating yeast infection and polyol... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Use of polyols in combating yeast infection and polyol..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Use of polyols in combating yeast infection and polyol... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2823233