Oral care foam based on lactoferrin and hydroxyapatite

Abstract

The invention refers to an oral care foam comprising lactoferrin and hydroxyapatite, as active ingredients, for preventing the formation of dental plaque and caries in the oral cavity and on the teeth surface.

Description

[0001] “ORAL CARE FOAM BASED ON LACTOFERRIN AND HYDROXYAPATITE”

[0002] STATE OF THE ART

[0003] The formation of the plaque in the mouth, in particular on the teeth surfaces and in interdental spaces, is absolutely physiological.

[0004] However, it is important to remove the dental plaque through careful dental hygiene in order to avoid tartar and caries formation which can lead to mouth diseases such as inflammation of the gums, ie., gingivitis, periodontitis and eventually teeth decay.

[0005] Nowadays there are several methods for preventing the formation of the plaque on the teeth surface and in the interdental spaces.

[0006] The most effective way to prevent the formation of plaque and tartar is periodical professional dental cleanings, which are performed by using specific instruments. More specifically, such instruments allow to scrape the surface of the teeth in order to mechanically remove the already formed plaque and the calcified spots.

[0007] The main drawback of professional dental cleanings for removing dental plaque lies in the fact that it is invasive, since it requires the simultaneous action of several instruments in the mouth of the patient.

[0008] Another drawback of professional dental cleanings lies in the fact that it must be performed by trained medical personnel, such as dentists or hygienists, and in an authorized dental practice.

[0009] A further drawback lies in the fact that periodical professional dental cleanings can be expensive.

[0010] Another way to prevent the formation of the dental plaque and tartar is the regular use of toothpaste with fluoride in it, which strengthens tooth enamel and reduces the risk of teeth decay.

[0011] However, at present, there is greater concern in society about the toxicity and longterm effects of fluoride. Another method for preventing the formation of dental plaque and tartar involves the incorporation of more effective tools in the daily oral hygiene routine. For example, the use of electric toothbrush has been proven to be more effective in removing plaque with respect to manual toothbrush. In addition, combined with flossing, it is possible to reach more hidden places for better results.

[0012] The main drawback of these solutions lies in the fact that it is difficult to be consistent with the use of this type of thorough cleaning practice every day, for compliance reasons and / or when traveling or, more generally, when away from home.

[0013] Another way for preventing dental plaque formation is the incorporation of a mouthwash or an oral care product in the daily oral hygiene routine.

[0014] However, the mouthwashes already available on the market must be used consistently, at least twice a day, to be effective. This can be a limit for people who have an active life and are often away from home.

[0015] Another drawback of these mouthwashes is that they are in liquid form, making it difficult to transport them and adapt their uses to different places away from home.

[0016] At present, some mouthwashes already available on the market for humans are intended to be used also in the veterinary field.

[0017] The drawbacks of these products lie in the fact that such mouthwashes are liquid, and therefore not easily administrable to animals, and, moreover, they are formulated with flavoring agents, such as mint or cinnamon, pleasant for human beings, but which can result in being distasteful for animals.

[0018] For all the above reasons, there is still the need of an oral care / mouthwash composition able to overcome all the prior art drawbacks, which can be employed by humans but also in the veterinary field. In particular, there is still the need of an oral care / mouthwash easy to use and to transport, stable to different ambient conditions, effective in the prevention of the plaque formation and in its removal, restoring and maintaining breath freshness.

[0019] OBJECTS OF THE INVENTION Object of the present invention is to provide an oral care foam formulation that can protect tooth enamel, prevents dental plaque and caries while maintaining a fresh breath for a long time.

[0020] Another object of the present invention is to provide an oral care foam formulation that provides for a non-invasive use.

[0021] Another object of the present invention is to provide an oral care foam formulation that can be used by a non-medical qualified people and in a non-medical context.

[0022] A further object of the present invention is to provide an oral care foam formulation which is cost-effective.

[0023] Another object of the present invention is to provide an oral care foam formulation which is easy to use even when the user is traveling or, in general, is away from home.

[0024] A further object of the present invention is to provide an oral care foam formulation which can be formulated with different flavors in order to result as pleasant not only for human beings but also for other animals such as, but not limited to, dogs, cats, and horses.

[0025] DESCRIPTION OF THE INVENTION

[0026] The objects stated above, as well as other objects, are achieved by means of the subject-matter of the present invention, z.e., an oral care foam formulation comprising lactoferrin in liposomes and hydroxyapatite, as active ingredients. As it will be shown in the experimental section, the oral care foam subject matter of the present invention is useful for the prevention of dental plaque and caries, for maintaining a healthy oral biofilm composition and for the treatment of mouth diseases.

[0027] As previously reported, caries is one of the most prevalent diseases affecting mankind. It is caused by a dysbiosis or imbalance of the oral biofilm.

[0028] The time at which caries develop and the biofilm becomes dysbiotic is shortly after eating and drinking; after consuming a carbohydrate rich food or beverage, the pH drops below 5.2 as a result of the acid producing bacteria. At this acidic pH, the hydroxyapatite, which forms the outer enamel matrix of the teeth, begins to be released from the surface of the enamel. It takes about 20 minutes for the saliva to neutralize the acid and stop the demineralization of the teeth. If enough of the tooth surface becomes demineralized, then decay forms which must then be removed and restored at a dental office.

[0029] In view of the above, there is a need for a new product such as oral care foam which can be used immediately after eating or drinking, while immediate brushing is not recommended due the risk of an increased mechanical damage to the teeth surface. In particular the oral care foam should both neutralize the acidic pH and prevent the acidophilic and acid producing bacteria from multiplying, which is what creates the imbalance of bacteria associated with a dysbiotic oral biofilm. Hence, the use of the oral care foam prevents the decay, remineralize the teeth and does not allow the cariogenic bacteria to multiply and quickly create unhealthy plaque. In the long run these actions will dramatically reduce the amount of tartar buildup on the tooth.

[0030] After intense research, the applicant was able to develop the oral care foam formulation of the present invention which is able to solve the above technical problems and shows all the advantages which will be clearly reported in the description and the following experimental part.

[0031] The lactoferrin comprised in the oral care foam of the present invention is conveyed by means of liposomes (ie., embedded in liposomes).

[0032] Lactoferrin is a multifunctional protein belonging to the transferrin family. In particular, it is a bilobed glycoprotein consisting of about 690 amino acids. Each lobe can reversibly bind one ferric ion. Lactoferrin is widely present in various secretory fluids, such the saliva, and represents one of the most important factors in the innated defense of the immunity system of the body, mainly at the mucosae level.

[0033] Lactoferrin is a natural chelator of metals, which shows antimicrobial activity against bacteria, fungi and pathogenic viruses that can infect the tissue. In more detail, lactoferrin inhibits the growth of these pathogenic microorganisms by chelating iron, which is a necessary co-factor for their development. In the present invention, lactoferrin is embedded in liposomes in order to prevent its direct bound to minerals that are naturally present in the formulation as well as in the oral environment and, once bounded to the lactoferrin, can impair its antibacterial activity.

[0034] Calcium, for example, is one of the main mineral constituents of hydroxyapatite and plays a key role in the structure and strength of bone and teeth. The association, inside the same liquid formulation, of lactoferrin and hydroxyapatite, without losing the antibacterial activity of the former, is made possible by its encapsulation in liposomes, which, as previously stated, prevents the bond between lactoferrin and calcium, of which hydroxyapatite is rich, leaving the bounding sites of lactoferrin free for the iron chelation and, as consequence, allows the maintenance of its antibacterial activity.

[0035] Lactoferrin provides unique advantage in the oral care thanks to its capacity to selectively attack the harmful bacteria, while keeping a healthy microbiome. Unlike some traditional mouthwashes which can indiscriminately kill both harmful and healthy bacteria, the specificity of lactoferrin in liposomes of the oral care foam of the present invention leads to a steadier and better equilibrium between the microorganisms of the oral cavity.

[0036] By selectively inhibiting the growth of harmful bacteria, like, for example but not limited to, Streprococcus mutans, Lactobacillus spp. and Porphyromonas gingivalis. while sparing the healthy bacteria, such as Streprococcus salivarius and Streprococcus mills. lactoferrin promotes a healthier microbial environment. This balanced microbic ecosystem is fundamental to keep a good oral care and to prevent the development of oral diseases like caries and periodontal diseases.

[0037] Moreover, the combination of effectiveness, specificity and safety of lactoferrin makes it a promising ingredient for oral hygiene products. Its ability of integrating the natural protective mechanisms of saliva brings about an improved biological equilibrium of oral cavity and contributes to the general oral health.

[0038] In the present invention, with the term “liposome” it is meant a vesicle consisting of at least one lipid bilayer and one core of aqueous solution encapsulated within the lipid bilayer. The lipids constituting the liposome bilayer (or liposome-forming lipids) can comprise mixtures composed essentially of phospholipids, such as for example phosphatidylcholine, and cholesterol in a lower amount. By way of example, lipids useful to constitute the lipid bilayer of liposome are a mixture of lipids comprising at least 50% phosphatidylcholine. The liposome can also comprise, in its lipid bilayer, further compounds of non-lipid nature, e.g., other organic compounds. For example, but not limited to, the liposomes can further comprise surfactants; according to the present invention, said surfactants may be ionic or non-ionic surfactants, preferably non-ionic, such as polysorbate 80 (also known as Tween 80®).

[0039] The lactoferrin comprised in the liposomes, according to the invention, is preferably encapsulated inside the lipid bilayer, and more preferably it is solubilized in the core of the aqueous solution which is typically enclosed within the lipid bilayer.

[0040] According to a preferred, non limiting, embodiment, the lactoferrin comprised in the liposomes is the one described in TH 02008901644744.

[0041] As previously stated, lactoferrin shows antimicrobial activity against bacteria, fungi and pathogenic viruses that can infect the tissue. In more detail, lactoferrin inhibits the growth of these pathogenic microorganisms by chelating iron, which is a necessary co-factor for their development.

[0042] The encapsulation of lactoferrin into liposomes prevents the glycoprotein’s degradation, thus ensuring higher stability and an improved bioavailability thereof as well as the maintenance of its antibacterial ability.

[0043] The liposomes according to the present invention can comprise, in addition to lactoferrin, at least a component selected from hyaluronic acid and / or polyethylene glycol (PEG), preferably PEG40.

[0044] According to a particular aspect of the invention, when the product comprises hyaluronic acid as component, PEG, preferably PEG 40 can also be comprised, and vice versa. In other words, the products of the invention can comprise lactoferrin and hyaluronic acid in combination with PEG, preferably PEG 40. When the product of the invention comprises hyaluronic acid, the hyaluronic acid can be inside or outside the lipid bilayer of liposomes. According to another aspect, when the product of the invention comprises hyaluronic acid, the hyaluronic acid is encapsulated inside the lipid bilayer and solubilized in the core of aqueous solution inside the liposome lipid bilayer.

[0045] When the products of the invention comprise PEG, preferably PEG 40, such PEG preferably forms a coating of the lipid bilayer of the liposomes.

[0046] According to a preferred aspect of the present invention, the lactoferrin, encapsulated in liposomes, is present in the oral care foam formulation in a percentage by weight, with respect to the total weight of the composition, between 0.1% and 1%.

[0047] The oral care foam, which is the subject-matter of the present invention, further comprises hydroxyapatite. Hydroxyapatite is the major component of teeth hard tissue, corresponding to 97% of the enamel and up to 70% of dentin.

[0048] According to a preferred aspect of the present invention, the hydroxyapatite is present in the oral care foam formulation in a percentage by weight, with respect to the total weight of the composition, between 0.1% and 2%.

[0049] According to a particular aspect, the oral care foam of the present invention can also comprise other active agents, such as aloe vera gel.

[0050] Aloe vera gel is a compound extracted from the Aloe barbaradensis plant. Said plant belongs to the Liliaceae family and contains various minerals and vitamins (including vitamin A, C, E, Bl, B2, B3, B6, choline, folic acid, alpha-tocopherol, beta-carotene, vitamin Bl 2).

[0051] According to a preferred aspect of the present invention, the aloe vera gel is present in the oral care foam formulation in a percentage by weight, with respect to the total weight of the composition, between 0.1% and 1%.

[0052] Optionally, the oral care foam of the present invention can also comprise arbutine, a natural substance deriving from hydroquinone. Specifically, arbutin is a glycosylated derivative of hydroquinone extracted from the bearberry plant, in particular from their leaves. According to another aspect, the oral care foam of the present invention can also comprise one or more ingredient responsible for its flavor and able to impart the sensation of prolonged freshness in the mouth. In more details, it can also comprise, for example, but not limited to, Menthol, Eucalyptus, Licorice, Green tea or Pomegranate.

[0053] According to a further aspect, the oral care foam of the present invention can include betaine (trimethylglycine) an amino acid derivative that occurs in plants, in particular in beetroots, used to moisturize and protect oral mucous membranes; and xanthan gum, used to stabilize the solution.

[0054] When present, trimethylglycine is in the oral care foam formulation in a percentage by weight, with respect to the total weight of the composition, between 1% and 5%.

[0055] When present xanthan gum is in the oral care foam formulation in a percentage by weight, with respect to the total weight of the composition, between 0.1% and 1%.

[0056] According to a preferred aspect, the oral foam formulation of the present invention includes hyaluronic acid. When present, said hyaluronic acid is preferably from 0.01% to 0.5% by weight to the total weight of the formulation;

[0057] The oral care foam, object of the present invention, can be formulated and produced following all the techniques known by the expert of the field and by adding all the necessary excipients normally employed in the related technical field. For example, but not limited to, water, organic short chain alcohols, wetting agents (humectants), preservatives, colorants, surfactants, foaming agents, thickeners, antioxidants, sweeteners, flavoring agents.

[0058] In a preferred aspect of the invention, the wetting agents are, for example but not limited to, sorbitol and glycerol. Also the betaine can act as a wetting agent.

[0059] For examples, the preservatives of the oral care foam can be a mixture of different compounds such as, but not limited to, phenoxyethanol, sodium benzoate, potassium sorbate, ethylhexylglycerin, benzyl alcohol, capryl glycol, ethylenediaminetetraacetic acid (EDTA), etcetera. In a preferred aspect of the present invention, the oral care foam comprises:

[0060] Lactoferrin encapsulated in liposomes from 0.1% to 1% by weight to the total weight of the formulation;

[0061] Hydroxyapatite from 0.1% to 2% by weight to the total weight of the formulation;

[0062] Betaine from 1% to 5% by weight to the total weight of the formulation;

[0063] Xantan gum from 0.1 to 1% by weight to the total weight of the formulation;

[0064] Aloe vera gel from 0.1% to 1% by weight to the total weight of the formulation;

[0065] Hyaluronic acid from 0.01% to 0.5% by weight to the total weight of the formulation; and other excipients such as, at least, water and preservatives as listed above, to reach 100%.

[0066] The oral care foam formulation of the present invention is preferably packed in cans, more preferably under pressure. In such aspect, the oral care foam formulation furthermore comprises propellants.

[0067] According to a preferred aspect, the oral care foam formulation of the present invention is in the form of a spray.

[0068] The oral care foam formulation of the present invention, comprising lactoferrin in liposomes and hydroxyapatite, is for use in the prevention of dental plaque formation and buildup and in the maintenance of a healthy oral biofilm composition in mammals, preferably humans.

[0069] According to another aspect, said oral care foam is intended for use in the veterinary field, for example but not limited to, in dogs, cats, horses, etcetera.

[0070] According to the latter aspect, the oral care foam formulation of the present invention can also comprise some ingredient responsible for imparting a flavor pleasant for animals, such as, but not limited to, liver flavor.

[0071] The oral care foam of the invention has a preventive and therapeutic properties towards diseases, and in particular towards mouth diseases. It has been surprisingly found that the combination of lactoferrin, in particular lactoferrin conveyed in liposomes, and hydroxyapatite in the product of the invention show a surprising preventive and therapeutic effect on dental plaque and caries. Such effects are demonstrated in the following experimental section, which exemplify the present invention without any limiting effect.

[0072] Besides its grater activity against the formation of the dental plaque, the oral care foam of the present invention shows also other advantages with respect to the prior art. In particular, it is easy to use and to transport, can be carried in suitcases and purses with no leaking problems, and used everywhere. The basic formulation of the oral care foam, composed by the active ingredients and the main excipients, can be adapted to the veterinary use, simply by substituting the flavoring ingredient with a flavor suitable for the target animal. Furthermore, the preferred foam formulation is easy to administer.

[0073] Another advantage of the oral care foam of the present invention is related to the treatment of the oral cavity in the pediatric and geriatric population. Both of these populations, in fact, often lack proper oral hygiene as they do not have the manual dexterity to perform effective brushing. Recently, a novel oral cleaning system was proposed for those subjects which consists in a “360° toothbrush” which utilizes a tray as brushing system that is capable of ultrasonically cleaning all the teeth at once in about 30 seconds without the need to use your hands. As it can be imagined, it is very difficult to use a toothpaste product with such a system, but the oral care foam of the present invention has been shown, on the contrary, to be ideal for this type of ultrasonic device. This is particularly helpful for parents of younger children, the disabled and nursing home populations.

[0074] Orthodontics is another area in which the oral care foam of the present invention has proven to be highly effective. Brackets on teeth make the mechanical removal of plaque far more difficult. This resultant increase in plaque leads to demineralization around these brackets which causes permanent white spots on the teeth. The oral care foam used after eating or drinking dramatically reduces the plaque buildup around brackets. Moreover, as previously reported, the oral care foam can be effectively and easily employed also in the veterinary field. For examples, dogs’ and cats’ oral health can be highly improved with the regular use of the oral care foam of the invention adapted, only in the flavor aspect, for pets. In fact, most pet owners do not regularly brush their pets’ teeth on a regular basis. As a result, plaque builds up which eventually leads to the buildup of tartar on the teeth. Over time, this buildup can cause periodontal disease which often results in tooth loss as well as increased systemic inflammation. This leads to greater risk of numerous chronic diseases such as diabetes, coronary artery disease and cancer. As dogs / cats age, it becomes far more dangerous to perform general anesthesia to remove these tartar deposits at a veterinary office. The oral care foam of the present invention provides an ideal technology that is both easy to implement on a daily basis and helps improve the overall health of pets.

[0075] The invention will be exemplified in the following experimental section for an exemplifying, and not limiting, purpose.

[0076] EXPERIMENTAL SECTION

[0077] Example 1

[0078] An oral care foam formulation according to the present invention was prepared with the components as reported in the following Table 1.

[0079] Table 1 : qualitative-quantitative composition of an oral care foam formulation according to the invention.

[0080] Manufacturing steps of the oral care foam reported in Table 1 and according to the invention.

[0081] 1. Preparation of the aqueous phase (1): mix together all aqueous components, previously weighted, at a low stirring rate, until the phase appears homogeneous, for example stir for not less than 5 minutes. Once reached a homogeneous phase, add the thickening agent (ie., xanthan gum) and wait for the gelation of the solution.

[0082] 2. Preparation of the surfactants’ mixture (2): mix together the previously weighed surfactants, at low stirring, until the mixture is homogeneous.

[0083] 3. Preparation of the extracts’ mixture (3): weigh and slightly stir together all extracts until a homogeneous mixture is obtained.

[0084] 4. Add the mixture of the extracts (3) on the surfactants’ mixture (2) and gently stir until the phase (3)+(2) appears homogeneous. Then add the aqueous phase (1) on phase (3)+(2) at a slight stirring rate until a homogeneous solution (3)+(2)+(l) is obtained.

[0085] 5. Measure the pH of the solution (3)+(2)+(l) and, if necessary, add sodium bicarbonate to reach a pH value around pH 6.

[0086] Note: The initial pH of the oral care formulation of Table 1 before correction with sodium bicarbonate was pH 5.78. Following addition of bicarbonate, the pH reached a value of pH 6.3.

[0087] Example 2

[0088] An oral care foam formulation according to the present invention was prepared with the components as reported in the following Table 2.

[0089] Table 2: qualitative-quantitative composition of an oral care foam formulation according to the invention.

[0090] The manufacturing process is consistent with the one reported for previous example 1. Example 3 : Study protocol on the effects of the oral foam formulation of the present invention on plaque buildup and oral biofilm composition in at-risk populations Method

[0091] The present study protocol is applied in order to determine the degree of reduction of plaque buildup and the influence on the composition of the oral biofilm of the oral foam formulation of the invention.

[0092] Specifically, the formulation prepared according to the table and the method described in Example 1 is intended to be used as test formulation in the below described protocol.

[0093] In particular, the study utilizes a randomized controlled trial design, with five different groups of at-risk population:

[0094] Group 1 - adolescents with a history of caries;

[0095] Group 2 - elderly and disabled individuals with inadequate dexterity for brushing; Group 3 - individuals wearing braces at risk for decalcification;

[0096] Group 4 - pets (dogs and cats);

[0097] Group 5 - individuals with xerostomia. Participants are assigned to either the treatment group, receiving the oral care foam formulation of the present invention (Table 1) containing hydroxyapatite and liposomal lactoferrin, or the control group, receiving a placebo oral foam.

[0098] More specifically, patients in the treatment group are treated with the oral care foam formulation of the present invention, administered in two sprays after meals, three times a day.

[0099] The study assesses plaque buildup and oral biofilm composition using standardized indices such as the Plaque index and an OraRisk Caries test, from OralDNA, to determine biofilm composition and caries risk.

[0100] The Plaque Index is generally used to quantify plaque accumulation on the tooth surfaces to assess oral hygiene status of a patient.

[0101] The OraRisk Caries Test (also known as OralDNA) is a molecular diagnostic test used to analyse the composition of the oral biofilm and determines the risk of developing caries.

[0102] Generally, the test is performed using a saliva or biofilm sample collected from the patient’s mouth. This sample is then subjected to Polymerase Chain Reaction (PCR) to identify the presence and the quantity of bacteria involved in the caries formation, such as Streptococcus mutans and Lactobacillus spp.

[0103] Additionally, this test can detect bacteria associated with periodontal diseases and other oral conditions. The purpose of this test is to provide a personalized assessment of caries risk based on the specific bacterial composition of the oral biofilm.

[0104] Data are then collected at baseline, after four weeks and again at eight weeks. In other words, data are collected at three different time points: TO (i.e. the condition before administration), T1 (i.e. after four weeks of treatment) and T2 (i.e. after eight weeks of treatment).

[0105] Statistical analysis are conducted to compare the outcomes between the treated and control groups and within each of the five study groups.

[0106] Results and comments

[0107] At time Tl, i.e. after four weeks of treatment, a marked difference is observed between the control and treatment groups.

[0108] More specifically, in the control group, no changes are observed with respect to the previous conditions, i.e. before the administration of the placebo formulation (TO).

[0109] Instead, in the patients administered with the oral care foam formulation of the present invention the physiological state of the oral microbiota is maintained.

[0110] More in detail, at Tl, proliferation of pathogenic bacteria is not observed in patients treated with the oral care foam of the invention.

[0111] Furthermore, patients who were administered with such oral care foam showed no plaque or caries formation after four weeks of treatment. At time T2, that is after eight weeks of treatment, the difference between the treated group and the control group is substantial.

[0112] More in detail, patients who were administered with the placebo formulation showed no changes with respect to the previous conditions, i.e. compared to the pre-treatment condition (TO) and after four weeks of treatment (Tl).

[0113] Instead, after eight weeks of treatment, the patients who received the oral care foam formulation of the present invention showed an improvement in the physiological bacterial flora, including but not limited to Streptococcus salivarius and Streptococcus mitis. After eight weeks of treatment, the patients who received the oral care foam formulation of the present invention also showed a notably inhibition of the proliferation of bacteria, such as Streptococcus mutans, keeping it within physiological limits.

[0114] Additionally, the dental surfaces of these treated patients appeared healthier, smoother, and more uniform with respect to the previous conditions (that is time TO and Tl) and with respect to the control group.

[0115] At T2, in the group of patients administered with the oral care foam of the present invention, a reduction in gum inflammation is also observed, which facilitates and accelerates the process of regeneration of gum tissue. After eight weeks of treatment, patients administered with the oral foam of the present invention also showed lower biofilm metabolic activity, due to the strong antimicrobial efficacy of the oral care foam itself.

[0116] As demonstrated by the above experimental part, the combined action of hydroxyapatite and liposomal lactoferrin is proved effective in suppressing pathogenic bacteria’s proliferation. Thus, the effects of hydroxyapatite and liposomal lactoferrin on plaque buildup and oral biofilm composition in at risk populations, were investigated.

[0117] According to the present invention, the use of the oral foam containing hydroxyapatite and liposomal lactoferrin offers significant benefits in maintaining oral microbiota balance and preventing the overgrowth of cariogenic bacteria in patients prone to periodontal diseases.

[0118] Always according to the invention, it was developed an innovative oral care interventions tailored to the specific needs of individuals with a history of caries, limited dexterity, orthodontic brackets, xerostomia and pets prone to calculus buildup.

[0119] The encapsulation of lactoferrin within liposomes protects the lactoferrin from denaturation and also enables its slow, controlled release, thereby preventing biofilm formation.

[0120] Liposomal lactoferrin plays a multifaceted role in treated patients; by way of example, but not limited to, liposomal lactoferrin exercises a bactericidal activity by directly interacting with bacterial cell walls, leading to the disruption of pathogenic microorganisms. In other words, the liposomal lactoferrin inhibits bacterial proliferation.

[0121] Furthermore, liposomal lactoferrin displays iron-chelating activity which allows to deprive bacteria of the essential iron needed for their growth.

[0122] Advantageously, this triple-action mechanism of liposomal lactoferrin not only limits harmful bacterial activity but also promotes a balanced oral microbiome. In addition, the hydroxyapatite contained in the formulation of the present invention compensate for dysbiosis resulting from prolonged intake of carbohydrates and acids. In fact, hydroxyapatite acts as a protective agent for the tooth surface, preventing excessive demineralization that typically occurs within the 20-minute window before saliva neutralizes the acidic environment generated by the consumption of carbohydrates and acids. By forming a protective layer on the dental enamel, hydroxyapatite promotes the restoration of the mineral balance, the filling micro-lesions and the sealing dentinal tubules, which contributes to a smoother, healthier tooth surface. For these reasons, in the treatment group there is a visible improvement in the appearance of the teeth, which appear healthier and smoother, with closed dentinal tubules that would otherwise expose the dentin. This also results in the alleviation of tooth sensitivity, as well as a significant reduction in the incidence of caries and plaque accumulation in the treated patients. In addition, it is observed that the remineralizing action of hydroxyapatite improves the natural defence mechanisms of the teeth, promoting general oral health in the treated patients.

[0123] In contrast, the control group shows less healthy dental conditions, characterized by an increased plaque accumulation, persistent dentinal hypersensitivity and a greater tendency to develop caries due to continued demineralization and bacterial activity. The anti-inflammatory properties of liposomal lactoferrin contribute to the reduction of gingival inflammation and the inhibition of plaque formation, supporting overall periodontal health. In untreated patients (i.e. the control group), lactoferrin levels in saliva are physiologically downregulated. However, since there is a high concentration of free iron in saliva, the low levels of lactoferrin quickly saturate, thus nullifying its antibacterial and antibiofilm action. This results in an increase of the inflammatory conditions related to uncontrolled bacterial growth, a condition characterized by heightened gingival inflammation, increased plaque and biofilm formation, and a greater risk of periodontal disease progression. In addition, excess free iron, due to lactoferrin deficiency, stimulates the synthesis of toxic oxygen radicals and the formation of pigments and the onset of black spot.

[0124] The lack of protective agents such as lactoferrin and hydroxyapatite in the control group resulted in an increase of the oral microbiome dysbiosis, causing the worsening of the overall oral health.

[0125] The proposed study aimed to investigate the effects of hydroxyapatite and liposomal lactoferrin on plaque buildup and oral biofilm composition in at risk populations.

[0126] This study suggests that the use of the oral foam containing hydroxyapatite and liposomal lactoferrin offers significant benefits in maintaining oral microbiota balance and preventing the overgrowth of cariogenic bacteria in patients prone to periodontal diseases.

[0127] The findings of this research contribute to the development of innovative oral care interventions tailored to the specific needs of individuals with a history of caries, limited dexterity, orthodontic brackets, xerostomia and pets prone to calculus buildup.

Claims

CLAIMS1. An oral care foam formulation comprising hydroxyapatite and liposomes containing lactoferrin.

2. The oral care foam formulation of claim 1 characterized in that said hydroxyapatite is from 0.1% to 2% by weight to the total weight of the formulation.

3. The oral care foam formulation of claim 1 or 2 characterized in that said liposomes containing lactoferrin comprise at least a component selected from hyaluronic acid and / or polyethylene glycol (PEG).

4. The oral care foam formulation of any one of the previous claims characterized in that said liposomes containing lactoferrin are from 0.1% to 1% by weight to the total weight of the formulation.

5. The oral care foam formulation of any one of the previous claims characterized in that further comprises betaine, preferably said betaine is from 1% to 5% by weight to the total weight of the formulation.

6. The oral care foam formulation of any one of the previous claims characterized in that further comprises Aloe vera gel, preferably, said Aloe vera gel is from 0.1% to 1% by weight to the total weight of the formulation.

7. The oral care foam formulation of any one of the previous claims characterized in that is packed in cans, preferably under pressure.

8. The oral care foam formulation of claims 1-7 characterized in that is in the form of a spray.

9. The oral care foam formulation of claim 1 for use in the prevention of dental plaque formation and buildup, and in the maintenance of a healthy oral biofilm composition, in humans.

10. The oral care foam formulation of claim 1 for use in the prevention of dental plaque formation and buildup, and in the maintenance of a healthy oral biofilm composition, in the veterinary field, preferably in cats, dogs and horses.

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