ES2685329B1 - Oral composition for deep mouth cleaning - Google Patents

Description

DESCRIPTION

Oral composition for deep mouth cleaning

The present invention relates to a combination of a probiotic (Streptococcus Salivaríus), a plant extract {Vaccinium Macrocarpon), xylitol and ubiquinol useful for deep cleansing (at the bacterial level) of the mouth, and for the treatment and / or prevention of abnormal conditions or oral diseases such as tartar plaque, gingivitis and periodontitis. It also refers to pharmaceutical or cosmetic compositions containing said combination of ingredients.

STATE OF THE TECHNIQUE

Oral hygiene is a problem of high magnitudes in any latitude and social stratum. Oral hygiene is usually deficient in the majority of the population, if by hygiene it refers only to brushing and removing food remains in the mouth. Oral hygiene should be at a bacterial level.

Poor oral hygiene at the bacterial level can lead to various oral diseases, such as gingivitis, which causes inflammation and bleeding of the gums and is caused by food remains that are trapped between the teeth, or periodontitis, which may initially occur with gingivitis, to then continue with a loss of collagen insertion, gingival recession and even bone loss.

A cause of gingivitis is plaque, which is a film formed by bacteria that forms in the teeth and gums. Plaque, if left untreated, produces toxins that can inflame or infect the gum tissue to cause gingivitis.

Sometimes these diseases can become chronic conditions that lead to severe effects on the oral environment and adjacent, even systemic environments. In the medical literature, articles in high-impact journals have appeared in recent times, showing obvious correlations between a certain oral bacterial load and acute infarction or cerebral stroke problems.

Oral hygiene is a problem of wide social diffusion (it is estimated that a percentage close to 40% has oral hygiene problems). Reversing the inertia of deficiencies in the way you care for your mouth is difficult, but you can supplement the hygiene in a deep and simple way.

There are sociocultural factors that predispose to have a deficient care of oral hygiene, however, in a way as simple as chewing gum, you can improve the hygienic efficiency offered by traditional methods.

Brushes, silks, interproximals and even mouthwashes are physical and chemical drag mechanisms. However, deep hygiene must be in the regulation of oral bacterial flora. Controlling this flora is the guarantee to prevent the progression of oral pathologies, or even pathologies of adjacent or systemic areas.

In view of the above, there is a need to provide new compositions that allow for proper oral hygiene at the bacterial level to prevent abnormal conditions or oral diseases such as plaque, gingivitis and periodontitis.

EXPLANATION OF THE INVENTION

The oral cavity houses a numerous and varied microbial flora. When the microbial balance is compromised, pathologies such as tooth decay or periodontitis can occur. The inventors have found that a combination of a probiotic (Streptococcus salivarius), a plant extract (Vaccinium macrocarpon), xylitol and ubiquinol is able to modify, in a controlled way, the oral bacterial flora achieving a balanced and healthy microbial balance. Therefore, this combination is useful for resolving oral and upper respiratory conditions, derived from the proliferation of pathogens that enter the body through the mouth.

Additionally, the combination of the invention can be formulated in the form of pharmaceutical or cosmetic compositions that can be prepared by simple and easily industrialized procedures. In addition, pharmaceutical or cosmetic compositions have the advantage that they can be administered orally in various formats, which facilitates acceptance and dosage for the patient.

The slow release of active ingredients in the oral cavity favors the rehydration of lyophilized probiotics and enables, by increasing temperature, the vitalization of these bacteria and their implantation in their own cavity. If the release were faster, there would be the possibility of being ingested and not being able to do its functionality in the oral environment.

On the other hand, the use of Vaccinium macrocarpon in oral environment, by the mechanism of action of inhibition of adhesion of bacteria fimbriated to mucous membranes and dental structure, prevents the appearance and greasing of the plaque. This plaque is the substrate for caries causing bacteria ( Streptococcus mutans), to adhere to the teeth and exert their destructive effect of tooth structure.

Thus, one aspect of the present invention relates to a combination comprising: a) Streptococcus Salivarius,

b) Vaccinium Macrocarpon extract ,

c) xylitol, and

d) ubiquinol.

Streptococcus Salivarius is a species of gram-positive spherical bacteria that mainly colonizes the mouth and upper respiratory tract of humans a few hours after birth, therefore, additional exposure to these bacteria is harmless. It produces two antimicrobial bacteriocins that have been shown to inhibit the growth of oral pathogens.

The incorporation of Vaccinium Macrocarpon extract into Streptococcus Salivarius makes it difficult for pathogenic bacteria to adhere and fix themselves in the oral cavity thanks to the condensed tannin it contains, which in turn facilitates colonization by the probiotic, and, at the same time, It allows the cleaning of the scale plate by the extract.

Ubiquinol (which is the totally reduced form of coenzyme Q10) is a fat-soluble benzoquinol found in all cell systems and in almost all cells, tissues and organs of mammals. Ubiquinol is acquired through biosynthesis (synthesized by the body itself) and by small contributions through the diet. By incorporating ubiquinol in the combination of the invention, a protective effect against gingivitis and peridontitis is also achieved.

Finally, xylitol, in addition to acting as a sweetener, also has a protective effect of enamel against acid attack.

The term " Vaccinium Macrocarpon extract " is used herein with its conventional meaning to refer to concentrated preparations obtained using extraction procedures from the Vaccinium Macrocarpon plant by appropriate means.

Vaccinium Macrocarpon extract , also known as large red cranberry or cranberry, is obtained from the fruit of the plant native to the wetlands of the northeastern United States and southeastern Canada. Suitable means for extracting the active ingredients include, for example, by entrainment with hydroalcoholic solvents.

The bioactive constituents of the plant include flavonol and anthocyanin glycosides, oligomeric proanthocyanidins, hydroxycinnamic acids and derivatives, other organic acids, iridoids, carotenoids and triterpenoids.

In a particular embodiment, optionally in combination with one or more characteristics of the various particular or preferred embodiments described above or subsequently, the Vaccinium Macrocarpon extract .

In another particular embodiment, optionally in combination with one or more features of the various particular or preferred embodiments described above or below, the Vaccinium Macrocarpon extract is the commercial product Pacran®

In another particular embodiment, optionally in combination with one or more characteristics of the various particular or preferred embodiments described above or subsequently, the Vaccinium Macrocarpon extract comprises proanthocyanidins.

In another particular embodiment, optionally in combination with one or more features of the various particular or preferred embodiments described above or below, the present invention relates to a combination as previously defined comprising a Vaccinium Macrocarpon extract obtainable through a procedure comprising: a) the extraction of the fruit from the Vaccinium Macrocarpon plant native to the wetlands of the northeastern United States and southeastern Canada, by dragging with hydroalcoholic solvents; b) separation of the extract obtained and c) removal of the solvent.

The term "obtainable" extract is used herein to define the extract by its method of obtaining and refers to the extract that can be obtained by the extraction procedure comprising steps a), b) and c) as defined above. For the purposes of the invention the expressions "obtainable", "obtained" and similar equivalent expressions are used interchangeably and, in any case, the expression "obtainable" encompasses the expression "obtained".

In a particular embodiment, optionally in combination with one or more features of the various particular or preferred embodiments described above or below, the invention relates to the combination comprising Streptococcus Salivarius, Vaccinium Macrocarpon extract , xylitol, and ubiquinol, where each of the components of the combination is present in an amount sufficient so that in combination with the other components a synergistic effect of the combination as a whole occurs.

The composition of the invention can be formulated in a pharmaceutical or cosmetic composition. Thus, another aspect of the invention relates to a pharmaceutical or cosmetic composition comprising an effective amount of a combination comprising Streptococcus Salivarius, Vaccinium Macrocarpon extract , xylitol, and ubiquinol, as defined above, and one or more excipients. and / or pharmaceutically or cosmetically acceptable carriers.

For the purposes of the present invention, an "effective amount" refers to the amount of active ingredients that, providing an effect after application, is low enough to avoid side effects at a reasonable benefit / risk ratio. In the case of pharmaceutical compositions, the effective amount is the "therapeutically effective amount" and refers to the amount of active ingredients of the pharmaceutical or cosmetic composition of the invention which, when administered to a subject, is sufficient to prevent the development. of, relieve to some extent, or treat one or more of the symptoms of the disorder or condition of interest.

The particular dose to be administered of the combination of the invention in the form of a pharmaceutical or cosmetic composition will be determined according to the particular circumstances of each case, including the patient's condition, age, duration of treatment, nature of any concurrent treatment, the specific combination. of active ingredients used, the specific excipients used and other factors known to the expert.

The term "pharmaceutically acceptable" carrier or excipient refers to excipients and / or carriers suitable for use in pharmaceutical technology for the preparation of compositions for medical use.

The term "cosmetically acceptable" carrier or excipient refers to excipients or carriers suitable for use in contact with mouth, tongue and teeth without toxicity, incompatibility, instability, improper allergic response, among others.

In a particular embodiment, optionally in combination with one or more features of the various particular or preferred embodiments described above or below, the pharmaceutical or cosmetic composition of the invention comprises between 0.5% and 2.5% by weight of Streptococcus. Salivarius', between 2% and 7% by weight of Vaccinium Macroarporr extract , between 0.5% and 3% by weight of xylitol; and between 0.001% and 2.5% by weight of ubiquinol; where the percentages are expressed by weight with respect to the total weight of the pharmaceutical or cosmetic composition.

The term "percentage (%)", when not explicitly specified, refers to the percentage of each ingredient of the pharmaceutical or cosmetic composition in relation to the total weight.

In a particular embodiment, optionally in combination with one or more features of the various particular or preferred embodiments described above or subsequently, the pharmaceutical or cosmetic composition of the invention defined above comprises: a) between 0.75% and 2.0 % more particularly between 1 and 2% by weight of Streptococcus Sativarius \ between 3% and 6% more particularly between 4 and 6% by weight of Vaccinium Macroarpon \ extract between 1% and 3% more particularly between 1.5 and 2.5% by weight of xylitol; and between 0.1% and 2.0% more particularly between 0.5 and 1.5%, by weight of ubiquinol; where the percentages are expressed by weight with respect to the total weight of the pharmaceutical or cosmetic composition.

In another particular embodiment, optionally in combination with one or more features of the various particular or preferred embodiments described above or below, the pharmaceutical or cosmetic composition of the invention comprises about 1.5% by weight of Streptococcus salivarius \ 5% in weight of Vaccinium macroarporr extract , 2% by weight of xylitol; and 1% by weight of ubiquinol, where the percentages are expressed by weight with respect to the total weight of the pharmaceutical or cosmetic composition.

In a particular embodiment, optionally in combination with one or more features of the various particular or preferred embodiments described above or below, the pharmaceutical or cosmetic composition of the invention is administered orally. More particularly, the pharmaceutical or cosmetic composition is in the form of tablets, candies or chewing gum. The administration in the form of chewing gum has the advantage that it allows the slow release of the assets thus prolonging the effect of the combination.

Pharmaceutical and cosmetic compositions can be prepared according to methods well known in the state of the art. One skilled in the art will know how to easily determine the appropriate excipients and / or carriers, and their amounts, according to the type of formulation to be prepared. The specific combination of excipients and / or carriers in the final composition will be determined largely by their chemical compatibility. In particular, said selection will take into account that the rest of the components do not interfere with the effect of the combination of Streptococcus Salivarius, Vaccinium Macrocarpon extract , xylitol, and ubiquinol.

The pharmaceutical and cosmetic compositions of the invention may comprise excipients and / or carriers such as gums, diluents, antiplatelet, lubricants, sweeteners, flavorings, and dyes, among others. Thus, in a particular embodiment, opclonally in combination with one or more characteristics of the various particular or preferred embodiments described above or subsequently, pharmaceutically or cosmetically acceptable excipients and / or carriers are selected from gums, diluents, antiplatelet, lubricants, sweeteners, flavorings, colorants and combinations thereof.

Examples of suitable gums include, but are not limited to, Xanthan gum, substances of plant origin from tropical trees such as Manilkara zapota (commonly known as chewing gum), acacia gum or synthetic elastomers such as butadiene-styrene copolymers, copolymers of isobutylene-isoprene, polyethylene, polyisobutylene, petroleum wax, polyvinyl acetate and mixtures thereof. The amount of gum in the pharmaceutical or cosmetic compositions of the invention is comprised between 75-90% by weight / weight.

Examples of suitable antiplatelet agents include, but are not limited to, silicon dioxide. The amount of antiplatelet in the pharmaceutical or cosmetic compositions of the invention is between 1.0-5% by weight / weight.

Examples of suitable diluents include, but are not limited to, microcrystalline cellulose and tricalcium phosphate. The amount of diluent in the pharmaceutical or cosmetic compositions of the invention is comprised between 10-15% by weight / weight.

Examples of suitable lubricants include, but are not limited to, magnesium stearate. The amount of lubricant in the pharmaceutical or cosmetic compositions of the invention is comprised between 0.5-2% by weight / weight.

Additionally, pharmaceutical compositions, preferably oral, or nutritional supplements of the invention may further comprise other ingredients, such as sweeteners (sorbitol); flavorings (strawberry, orange); dyes, such as red iron oxide (E-172), titanium dioxide (E-171) and carmoisin red (E-122); sweeteners and other components commonly used in oral formulations.

As previously indicated, the combination of Streptococcus Salivarius, Vaccinium Macrocarpon extract, xylitol, and ubiquinol is useful for resolving oral and upper respiratory conditions, derived from the proliferation of pathogens that enter the body through the mouth.

Thus, the present invention also relates to the use of a combination comprising Streptococcus Salivarius, Vaccinium Macrocarpon extract , xylitol, and ubiquinol, for the preparation of a medicine for the treatment and / or prevention of abnormal conditions or oral diseases.

This aspect of the invention can also be defined as a combination comprising Streptococcus Salivarius, Vaccinium Macrocarpon extract , xylitol, and ubiquinol, for use in the treatment and / or prevention of abnormal conditions or oral diseases.

Also part of the invention is a method for the treatment and / or prevention of abnormal conditions or oral diseases, which comprises administering to a subject, preferably a human being, an effective amount of a combination of Streptococcus Salivarius , Vaccinium Macrocarpon extract , xylitol , and ubiquinol, and one or more pharmaceutically acceptable excipients and / or carriers.

In a particular embodiment, optionally in combination with one or more features of the various particular or preferred embodiments described above or subsequently, the abnormal condition or oral disease is selected from tartar plaque, gingivitis and periodontitis.

In addition, the combination of the invention can also be used for cosmetic purposes for the oral cavity in general, to improve the dental appearance and / or the sensation of fresh mouth. Therefore, the invention also relates to the cosmetic use of a combination comprising Streptococcus Salivarius, Vaccinium Macrocarpon extract , xylitol, and ubiquinol, for mouth care and more particularly for deep mouth cleaning.

Also part of the invention is a cosmetic method for oral care of the mouth (and more particularly for deep cleaning of the mouth) in a subject in need, including a human, said method comprising administering to said subject, including a being human, an effective amount of the combination of the first aspect, together with cosmetically acceptable excipients and / or carriers.

The term "cosmetic" as used herein is intended to designate a use intended, primarily, to provide an aesthetic and / or comfort effect, in particular, for the care of the mouth in general, and more particularly for the deep cleaning of the mouth, to improve the appearance of teeth and / or fresh mouth feeling, etc ...

In the context of the present invention, when the combination of the invention is used for cosmetic purposes, it is not intended to include any therapeutic use. Cosmetic use is particularly aimed at individuals who do not suffer from abnormal conditions or oral diseases such as tartar plaque, gingivitis or peridontitis and the like. When the combination of the invention is used for cosmetic purposes, the combination is part of a cosmetic composition as defined above.

Throughout the description and the claims the word "comprises" and its variants are not intended to exclude other technical characteristics, additives, components or steps. In addition, the word "comprises" includes the case "consists of." For those skilled in the art, other objects, advantages and features of the invention will be derived partly from the description and partly from the practice of the invention. Examples are provided by way of illustration, and are not intended to be limiting of the present invention In addition, the present invention covers all possible combinations of particular and preferred embodiments indicated herein.

EXAMPLES

Preparation of a composition according to the invention

The following chewing gum composition was prepared containing the following components:

• 1.5% by weight of Streptococcus Salivaríus (lyophilized)

• 5% by weight of Vaccinium Macrocarpon (Pacran)

• 2% by weight of xylitol

• 1% by weight of ubiquinol

• 85% by weight of chewing gum mass {acacia gum)

• 2% by weight of flavoring (strawberry or orange)

• 1.5% by weight silicon dioxide

• 2% by weight magnesium stearate

The procedure for preparing this composition was as follows:

1. The cranberry extract, ubiquinol and Streptococcus Salivarius were incorporated in a mixing vessel and mixed for 15 minutes.

2. The strawberry or orange flavoring, the sweetener (xylitol) and the antiplatelet (silicon dioxide) were added to the above mixture and mixed for 10 minutes.

3. To the above mixture, 25% of the weight of the chewing gum was incorporated and mixed for 5 minutes.

4. To the previous mixture, another 25% of the weight of the chewing gum was incorporated and mixed for 5 minutes.

5. To the previous mixture, the rest of the weight of the chewing gum was incorporated and mixed for 10 minutes.

6. On the above mixture, magnesium stearate was incorporated and mixed for 5 minutes.

7. The mixture was compressed by direct compression.

This mixture can be used in different final pharmaceutical forms as appropriate. The final mixture accepted for manufacturing must be reserved in a refrigerator below 5 degrees Celsius until the moment of compression. The compression of the mixture must be done guaranteeing conditions of low temperature, low humidity and with the mixture just extracted from the refrigerator.

How to use for a composition of the invention in the form of chewing gum Chew the gum for a minimum of about 10 minutes to ensure that the active ingredients are released from the gum mass. It is enough to take it once a day and maintain the initial treatment for three months. From then on the gum intake should be spaced and done at regular and alternate periods.

Separate the gum from all types of rinses, mouthwashes and antibiotics. If for other reasons therapy with systemic antibiotics should be instituted, treatment should be initiated from the beginning.

Claims (10)

1. A combination comprising: a) Streptococcus Salivarius, b) Vaccinium Macrocarpon extract , c) xylitol, and d) ubiquinol. 2. A pharmaceutical or cosmetic composition comprising an effective amount of the combination defined in claim 1, and one or more pharmaceutically or cosmetically acceptable excipients and / or carriers. 3. The pharmaceutical or cosmetic composition according to claim 2, comprising between 0.5% and 2.5% by weight of Streptococcus Salivarius; between 2% and 7% by weight of Vaccinium Macroarpon extract ; between 0.5% and 3% by weight of xylitol; and between 0.001% and 2.5% by weight of ubiquinol; where the percentages are expressed by weight with respect to the total weight of the pharmaceutical or cosmetic composition. 4. The pharmaceutical or cosmetic composition according to claim 3, which comprises about 1.5% by weight of Streptococcus Salivarius; 5% by weight of Vaccinium Macroarpon extract ; 2% by weight of xylitol; and 1% by weight of ubiquinol. 5. The pharmaceutical or cosmetic composition according to any of claims 2-4, which is administered orally. 6. The pharmaceutical or cosmetic composition according to claim 5, which is in the form of a tablet, caramel or chewing gum. 7. The pharmaceutical or cosmetic composition according to any of claims 2-6, wherein the pharmaceutically or cosmetically acceptable excipients and / or carriers are selected from gums, diluents, antiplatelet, lubricants, sweeteners, flavorings, colorants and combinations thereof. 8. Use of the combination as defined in claim 1, for the preparation of a medication for the treatment and / or prevention of abnormal conditions or oral diseases. 9. Use according to claim 8, wherein the abnormal condition or oral disease is selected from tartar plaque, gingivitis and periodontitis. 10. Use of the combination as defined in claim 1, for the preparation of a medicament for deep cleaning of the mouth at the bacterial level.