Cosmetic composition for the oral cavity

Abstract

A cosmetic composition for the oral cavity, comprising cross-linked hyaluronic acid, a product comprising the composition, and the cosmetic use of the composition or product to clean, scent, modify the appearance, protect, keep in good condition, or correct odors of the oral cavity and in particular of teeth, gums and mucosae.

Description

[0001] COSMETIC COMPOSITION FOR THE ORAL CAVITY

[0002] The present invention relates to a cosmetic composition for the oral cavity.

[0003] Oral hygiene is the practice that allows to keep the oral cavity clean, reducing the risk of disorders and other problems (for example, halitosis) through regular cleaning of the teeth at home and / or professionally. It is important that oral hygiene is practiced on a regular basis to allow the prevention of dental diseases and bad breath. The most common dental disorders are tooth decay (caries and dental infiltrations) and gum diseases, such as gingivitis and periodontitis.

[0004] Cosmetic and oral hygiene products such as mouthwashes, gels, serums, creams, toothpastes, and oral sprays are known.

[0005] Hyaluronic acid is a naturally occurring linear polysaccharide found in the extracellular matrix of various tissues. It is synthesized by cells such as fibroblasts, keratinocytes, and endothelial cells of the skin. The molecular weight of hyaluronic acid can vary widely, from 5 kilodaltons (kDa) to 2,000 kDa, depending on the number of repeating disaccharide units it contains.

[0006] One of the most well-known functions of hyaluronic acid is its ability to moisturize the skin. Hyaluronic acid is in fact highly effective at trapping water, which gives it a key role in skin health and appearance, including reducing the appearance of wrinkles and accelerating wound healing. In addition to these benefits, hyaluronic acid-based formulations have also shown remarkable efficacy in treating a variety of inflammatory skin conditions (Litwiniuk et al., 2016: “Hyaluronic acid in inflammation and tissue regeneration.” Wounds, 28(3) pages 78-88).

[0007] Hyaluronic acid and its binding proteins, at the cellular level, regulate the expression of inflammatory genes, the recruitment of inflammatory cells, and the release of inflammatory cytokines and can attenuate the course of inflammation, providing protection against tissue damage. A growing body of evidence suggests that cellular responses depend on the molecular weight of hyaluronic acid (Petrey et al., 2014: “Hyaluronan, a crucial regulator of inflammation.” Front Immunology 2014 Mar 11:5: 101. doi: 10.3389 / fimmu.2014.00101. eCollection 2014).

[0008] Studies suggest that low-molecular-weight hyaluronic acid (LMW- HA) can induce inflammatory responses, while high-molecular-weight hyaluronic acid (HMW-HA) acts as an anti-inflammatory factor (Campo et al., 2010: “Molecular size hyaluronan differently modulates toll-like receptor-4 in LPS-induced inflammation in mouse chondrocytes.” Biochimie, 92(2)(2010), pages 204-215).

[0009] Hyaluronic acid is an increasingly common ingredient in a wide range of cosmetic products for oral cavity care and hygiene. Leading brands of toothpaste and mouthwash use formulations containing hyaluronic acid for their ability to improve gum health, reduce sensitivity, and provide a protective barrier (Al-Khateeb et al., 2020: “Biological molecules in dental applications: hyaluronic acid as a companion biomaterial for diverse dental applications”. Heliyon, vol. 6 Issue 4, April 2020 and Casale et al., 2016: “Hyaluronic acid: Perspectives in dentistry. A systematic review.” International Journal of Immunopathology and Pharmacology, Vol. 29, Issue 4, pages 572-582). Hyaluronic acid, thanks to its viscoelastic and physical properties, forms a protective barrier on the inflamed oropharyngeal mucosa; in fact, being a hydrophilic molecule, it is able to absorb water up to 1000 times its volume, providing a sort of gel.

[0010] Hyaluronic acid is also used as an adjuvant in the management of conditions such as recurrent aphthous stomatitis and temporomandibular disorders.

[0011] However, when formulating hyaluronic acid-based cosmetic products for the oral cavity, it is necessary to reduce the degradation of high molecular weight hyaluronic acid (HMW-HA) to low molecular weight hyaluronic acid (LMW-HA) (Schmidt et al., 2023: “Low, medium, and high molecular weight hyaluronic acid effects on human dental pulp stem cells in vitro”. International Journal of Biological Macromolecules 2023 Vol. 253, Part 6), since low molecular weight hyaluronic acid, as described above, can induce an inflammatory response. Degradation occurs mainly by bacterial degradation by Bacteroides spp. and enzymatic degradation by the hyaluronidase that is present in saliva.

[0012] The aim of the present invention is therefore to provide a cosmetic composition for the oral cavity with prolonged moisturizing and normalizing action.

[0013] Within the scope of this aim, an object of the invention is to provide a cosmetic composition comprising hyaluronic acid that is resistant to degradation by bacteria and enzymes present in the oral cavity.

[0014] Another object of the invention is to provide a cosmetic composition for the oral cavity that has an anti-inflammatory action.

[0015] Another object of the invention is to provide a cosmetic composition for the oral cavity that has an anti-edematous action.

[0016] Another object of the invention is to provide a cosmetic composition for improving the health, modifying the appearance, protecting, maintaining in good condition and / or correcting the odors of the oral cavity and in particular of the teeth, gums and oral mucosa.

[0017] Not least object of the invention is to provide a cosmetic composition for the oral cavity which is highly reliable, relatively easy to manufacture and at competitive costs.

[0018] This aim, as well as these and other objects that will become better apparent hereinafter are achieved by a cosmetic composition for the oral cavity comprising cross-linked hyaluronic acid.

[0019] The aim and objects of the invention are also achieved by an oral cavity product comprising the cosmetic composition according to the invention, wherein said product is selected from the group consisting of a mouthwash, a gel, a serum, a cream, a toothpaste powder, and an oral spray. Finally, the aim and objects of the invention are achieved also by the use of a cosmetic composition or of a product according to the invention for at least one cosmetic treatment of the oral cavity selected from the group consisting of antiseptic treatment, pain-relieving treatment, brightening treatment, regenerating treatment, anti-inflammatory treatment, antimicrobial treatment, antioxidant treatment, sanitizing treatment, soothing treatment, moisturizing treatment, uniforming treatment, and anti- aphthous treatment.

[0020] As is known, the oral cavity has particular critical issues related to the bacterial and enzymatic degradation of hyaluronic acid. In fact, it is characterized by particular conditions of pH, salivary flow, oral microbiome, exposure to oral hygiene products and brushing, any oral diseases, chemical products and drugs, eating habits and the acid-base potential of the diet, all factors that influence the degradation of hyaluronic acid.

[0021] Cross-linked hyaluronic acid is produced by linking linear hyaluronic acid molecules together. This process, known as cross-linking, makes hyaluronic acid more resistant to enzymatic degradation.

[0022] Various types of cross-linking agents that can be used in this process are known to the person skilled in the art. For example:

[0023] - 1 ,4-butanediol diglycidyl ether (BDDE): a common cross-linking agent that is relatively safe and effective, and

[0024] - polyethylene glycol (PEG): a non-toxic and biocompatible crosslinking agent.

[0025] In a preferred embodiment of the composition according to the invention, the cross-linked hyaluronic acid is present in an amount comprised between 0.0001% and 10%, preferably between 0.01% and 1% by weight relative to the weight of the composition.

[0026] Preferably, the cosmetic composition for the oral cavity according to the invention further comprises at least one compound selected from the group consisting of an antiseptic, an analgesic, a hydroxyapatite, a lightening peptide, a regenerating peptide, an anti-inflammatory peptide, an antimicrobial peptide, a ceramide and an antioxidant.

[0027] An example of an active ingredient with antiseptic activity is cetylpyridinium chloride (CPC).

[0028] Among pain-relieving compounds, various natural active ingredients and natural soothing extracts are known to the person skilled in the art which alleviate the pain and discomfort of irritated gums.

[0029] Hydroxyapatite is used to strengthen tooth enamel.

[0030] There are also various peptides commonly used in oral hygiene products that can be incorporated into preferred embodiments of the invention. For example:

[0031] - lightening peptides, which are used for stain reduction,

[0032] - regenerating peptides that stimulate and increase tissue regeneration,

[0033] - anti-inflammatory peptides such as, for example, decapeptide-23, palmitoyl tripeptide-8, acetyl hexapeptide-49, acetyl tetrapeptide- 15,

[0034] - antimicrobial peptides,

[0035] - antiallergenic peptides such as, for example, acetyl dipeptide 1- cetyl, acetyl tetrapeptide-22, acetyl tetrapeptide-40, acetyl heptapeptide-4, heptapeptide 10, decapeptide-23, palmitoyl tripeptide-8 and acetyl tetrapeptide-2,

[0036] - peptides that promote cell repair, such as, for example, acetyl tetrapeptide-2,

[0037] - peptides with anti-itching activity, such as, for example, acetyl hexapeptide-49 and acetyl tetrapeptide-15.

[0038] The cosmetic composition for the oral cavity according to the invention may further comprise ceramides, antioxidants, fluorine and fluorides, ozonized oils, fermented oils, amino acids, lactoferrin, zinc lactate, xylitol, sorbitol and other polyols.

[0039] The invention will now be described with reference to the following non-limiting example.

[0040] EXAMPLE 1: EFFECT OF CROSS-LINKED HYALURONIC ACID IN A GEL FOR THE ORAL CAVITY

[0041] To evaluate the effect of cross-linked hyaluronic acid in a composition for oral hygiene, two gel formulations were prepared, the first incorporating non-cross-linked hyaluronic acid with medium-high molecular weight, between 1,200 and 1,500 kDa (preparation 1), and the second incorporating cross-linked hyaluronic acid with a molecular weight greater than or equal to 3,000 kDa (preparation 2).

[0042] To prepare 1 kg of preparation 1, 967.34 g of purified water was used, heated to 33±3°C, in which 4 g of acrylates / C 10-30 alkyl acrylate crosspolymer (Carbopol®ultrez 21, Lubrizol) and 7 g of carbomer (Carbopol®ultrez 30, Lubrizol) were dispersed under turboemulsion until a homogeneous mass without agglomerates was obtained.

[0043] Subsequently, 10 g of a preservative consisting of a mixture of benzyl alcohol and dehydroacetic acid marketed under the name ISOCIDE®BAS (LEHVOSS Italia SRL) and 1.25 g of pentylene glycol (Microcare Emollient PTG, Thor Specialties LLC) were added under agitation until complete solubilization was achieved.

[0044] Next, 1.25 g of sodium hyaluronate (Phylcare® Sodium Hyaluronate MW 95, Bloomage Biotechnology Corp., Ltd) was added to the solution, keeping the mixture under agitation for 45 minutes. Finally, the solution was brought to pH = 6 with the addition of 9.16 g of a 30% sodium hydrate solution (ACEF SpA).

[0045] To prepare 1 kg of preparation 2, 919.84 g of purified water was used, heated to 33±3°C, in which 4 g of acrylates / C 10-30 alkyl acrylate crosspolymer (Carbopol®ultrez 21, Lubrizol) and 7 g of carbomer (Carbopol®ultrez 30, Lubrizol) were dispersed under turboemulsion until a homogeneous mass without agglomerates was obtained.

[0046] Next, 10 g of a preservative consisting of a mixture of benzyl alcohol and dehydroacetic acid marketed under the name ISOCIDE®BAS (LEHVOSS Italia SRL) were added under agitation until complete solubilization was achieved.

[0047] Next, 50 g of Phylcare® HyacrossTM TL 100 (Bloomage Biotechnology Corp., Ltd) (equivalent to 1.25 g of crosspolymer sodium hyaluronate, 1.25 g of pentylene glycol, and 47.5 g of water) was added while continuing agitation for 45 minutes. Finally, the solution was brought to pH = 6 by adding 9.16 g of a 30% sodium hydrate solution (ACEF SpA).

[0048] Both preparations were incubated for 24 hours with a buffer solution (1.5% w / v) at pH 7 and pH 5, respectively, at 37°C with 50 units / ml of hyaluronidase (HAase) (stock solution of HAase type IV-S powder, 1045 units / mg in PBS, purchased from SIGMA Aldrich).

[0049] The goal was to test resistance under physiological conditions (pH 7), as well as to simulate the acidic pH situation (pH 5) due to the particular conditions of the oral cavity after the ingestion of carbohydrate-containing food, in which the pH tends to decrease as reported in the literature (Bradshaw DJ, Analysis of pH-Driven Disruption of Oral Microbial Communities in vitro, Caries Res 1998;32:456-462).

[0050] The enzymatic degradation reaction causes the release of a degradation product, glucuronic acid (GlcA), the quantity of which was determined by a colorimetric carbazole assay (Bitter, T.; Muir, H. A modified uronic acid carbazole reaction. Anal. Biochem. 1962, 4, 330-334).

[0051] It was observed that at pH 5, the degradation of hyaluronic acid in preparation 1 is surprisingly greater than that in preparation 2, suggesting a greater resistance of this compound with respect to the linear form in the oral environment after the ingestion of carbohydrates, i.e., when oral care products are usually used.

[0052] In practice it has been found that the invention fully achieves the intended aim and objects, since it provides a cosmetic composition for the oral cavity characterized by the beneficial effects of hyaluronic acid and by a drastic reduction of the side effects associated with the degradation of medium or high molecular weight hyaluronic acid.

[0053] The cosmetic composition thus conceived is susceptible to numerous modifications and variations, all of which are within the scope of the accompanying claims; all the details may furthermore be replaced with other technically equivalent elements.

[0054] In practice, the materials used, as well as the dimensions, may be any according to the requirements and the state of the art.

[0055] The disclosures in Italian Patent Application No. 102024000015847, from which this application claims priority, are incorporated herein by reference.

Claims

CLAIMS1. A cosmetic composition for the oral cavity, comprising crosslinked hyaluronic acid.

2. The cosmetic composition according to claim 1, wherein the crosslinked hyaluronic acid is present in an amount comprised between 0.0001% and 10%, preferably between 0.01% and 1% by weight relative to the weight of the composition.

3. The cosmetic composition according to claim 1 or 2, further comprising at least one compound chosen from the group consisting of an antiseptic, an analgesic, a hydroxyapatite, a lightening peptide, a regenerating peptide, an anti-inflammatory peptide, an antimicrobial peptide, a ceramide, and an antioxidant.

4. A product for the oral cavity comprising the cosmetic composition according to any one of the preceding claims, wherein said product is selected from the group consisting of a mouthwash, a gel, a serum, a cream, a toothpaste powder, and an oral spray.

5. Use of a cosmetic composition according to any one of claims 1 to 3 or of a product according to claim 4, for at least one cosmetic treatment of the oral cavity selected from the group consisting of antiseptic treatment, pain-relieving treatment, brightening treatment, regenerating treatment, antiinflammatory treatment, antimicrobial treatment, antioxidant treatment, sanitizing treatment, soothing treatment, moisturizing treatment, uniforming treatment, and anti-aphthous treatment.