Prevention of Dental Caries: A Review on the Improvements of Toothpaste Formulations from 1900 to 2023.

Modern toothpastes are complex formulations with various ingredients. The aim of this study was to analyze the improvement of toothpaste formulations from 1900 to 2023 focusing on active ingredients with remineralizing, antibacterial, or plaque-removing effects, and to discuss their influence on caries prevention. For this, worldwide patent applications were searched using the international database Espacenet from the European Patent Office. Additionally, toothpaste products were searched using the Mintel product database from 1996 to 2023. The searched ingredients were (in alphabetical order): calcium carbonate, calcium phosphates, hydrated silica, sodium fluoride, sodium lauryl sulfate, triclosan, xylitol, and zinc salts as they are known from the scientific literature to be remineralizing or antibacterial/antiplaque agents. It was shown that the number of patent applications containing these ingredients significantly increased since the 1970s. As these ingredients have remineralizing, antibacterial, or plaque-removing effects, they all can contribute to caries prevention. In conclusion, and within the limitations of this approach, this study shows that toothpaste formulations have greatly improved over the past decades by using various active anticaries ingredients.

Caries Etiology and Preventive Measures.

Caries is a widespread disease in both children and adults. Caries is caused by the conversion of fermentable carbohydrates by plaque bacteria into acids on the tooth surface. Thus, it is important to focus on sugar reduction and plaque control. For efficient plaque removal/control, state-of-the-art toothpastes contain various active ingredients such as antimicrobial agents (e.g., chlorhexidine, stannous salts, and zinc salts), abrasives (e.g., calcium carbonate, calcium phosphates, and hydrated silica), surfactants (e.g., sodium lauryl sulfate and sodium methyl cocoyl taurate), and natural compounds (e.g., polyphenols and xylitol). Agents with pH-buffering and calcium-releasing properties (e.g., calcium carbonate and calcium phosphates) and biomimetic actives (e.g., hydroxyapatite) reverse the effects of the acids. Additionally, modern toothbrushes (i.e., electric toothbrushes) as well as dental floss and interdental brushes significantly help remove plaque from dental surfaces including interproximal surfaces. In conclusion, modern concepts in caries prevention should focus not only on tooth remineralization alone but also on the control of all the key factors involved in caries development.

Doses of fluoride toothpaste for children up to 24 months.

AIM: The aim of this study was to test the dose of fluoride toothpaste by parents for their children aged up to 24 months. METHODS: Parents who use fluoride toothpastes for their children were asked to dose two commercially available toothpastes (A and B) with 1000 ppm fluoride each for their children as they would normally do at home. The toothpaste amounts were weighed, and as reference, the weight of an 'optimal' grain of rice-size amount of each toothpaste was used. RESULTS: 61 parents dosed a mean of 0.263 ± 0.172 g toothpaste A and 0.281 ± 0.145 g toothpaste B. The parents' mean doses were 5.9 times higher for toothpaste A and 7.2 times higher for toothpaste B than an 'optimal' grain of rice-size amount (the reference dose as recommended). The difference between parent's and reference dose was statistically significant (p < 0.001). Moreover, 39.3% of parents were not aware about conditions of use and warnings that have to be printed on the package of fluoride toothpastes. CONCLUSION: In this study, parents significantly overdosed the toothpaste for their children. To avoid fluoride intake from toothpaste, parents can choose fluoride-free alternatives for the oral care of their infants and toddlers.

The composition of the dental pellicle: an updated literature review.

Background: The dental pellicle is a thin layer of up to several hundred nm in thickness, covering the tooth surface. It is known to protect the teeth from acid attacks through its selective permeability and it is involved in the remineralization process of the teeth. It functions also as binding site and source of nutrients for bacteria and conditioning biofilm (foundation) for dental plaque formation. Methods: For this updated literature review, the PubMed database was searched for the dental pellicle and its composition. Results: The dental pellicle has been analyzed in the past years with various state-of-the art analytic techniques such as high-resolution microscopic techniques (e.g., scanning electron microscopy, atomic force microscopy), spectrophotometry, mass spectrometry, affinity chromatography, enzyme-linked immunosorbent assays (ELISA), and blotting-techniques (e.g., western blot). It consists of several different amino acids, proteins, and proteolytic protein fragments. Some studies also investigated other compounds of the pellicle, mainly fatty acids, and carbohydrates. Conclusions: The dental pellicle is composed mainly of different proteins, but also fatty acids, and carbohydrates. Analysis with state-of-the-art analytical techniques have uncovered mainly acidic proline-rich proteins, amylase, cystatin, immunoglobulins, lysozyme, and mucins as main proteins of the dental pellicle. The pellicle has protective properties for the teeth. Further research is necessary to gain more knowledge about the role of the pellicle in the tooth remineralization process.

Caries-preventing effect of a hydroxyapatite-toothpaste in adults: a 18-month double-blinded randomized clinical trial.

Background: Dental caries is a worldwide challenge for public health. The aim of this 18-month double-blinded, randomized, clinical trial was to compare the caries-preventing effect of a fluoride-free, hydroxyapatite toothpaste (test) and a toothpaste with sodium fluoride (1450 ppm fluoride; positive control) in adults. Methods: The primary endpoint was the percentage of subjects showing no increase in overall Decayed Missing Filled Surfaces (DMFS) index. The study was designed as non-inferiority trial. Non-inferiority was claimed if the upper limit of the exact one-sided 95% confidence interval for the difference of the primary endpoint DMFS between test and control toothpaste was less than the predefined margin of non-inferiority (Δ ≤ 20%). Results: In total, 189 adults were included in the intention-to-treat (ITT) analysis; 171 subjects finished the study per protocol (PP). According to the PP analysis, no increase in DMFS index was observed in 89.3% of subjects of the hydroxyapatite group and 87.4% of the subjects of the fluoride group. The hydroxyapatite toothpaste was not statistically inferior to a fluoride toothpaste with regard to the primary endpoint. Conclusion: Hydroxyapatite was proven to be a safe and efficient anticaries agent in oral care. Clinical trial registration: NCT04756557.

N,N-Dimethylglycine Sodium Salt Exerts Marked Anti-Inflammatory Effects in Various Dermatitis Models and Activates Human Epidermal Keratinocytes by Increasing Proliferation, Migration, and Growth Factor Release.

N,N-dimethylglycine (DMG) is a naturally occurring compound being widely used as an oral supplement to improve growth and physical performance. Thus far, its effects on human skin have not been described in the literature. For the first time, we show that N,N-dimethylglycine sodium salt (DMG-Na) promoted the proliferation of cultured human epidermal HaCaT keratinocytes. Even at high doses, DMG-Na did not compromise the cellular viability of these cells. In a scratch wound-closure assay, DMG-Na augmented the rate of wound closure, demonstrating that it promotes keratinocyte migration. Further, DMG-Na treatment of the cells resulted in the upregulation of the synthesis and release of specific growth factors. Intriguingly, DMG-Na also exerted robust anti-inflammatory and antioxidant effects, as assessed in three different models of human keratinocytes, mimicking microbial and allergic contact dermatitis as well as psoriasis and UVB irradiation-induced solar dermatitis. These results identify DMG-Na as a highly promising novel active compound to promote epidermal proliferation, regeneration, and repair, and to exert protective functions. Further preclinical and clinical studies are under investigation to prove the seminal impact of topically applied DMG-Na on relevant conditions of the skin and its appendages.

pH-equilibration of human hair: Kinetics and pH-dependence of the partition ratios for H+ - and OH- -ions based on a Freundlich isotherm.

Hair is an insoluble, fibrous, α-keratinous, protein composite material, providing outer coverage, e.g., for mammals. In the context of a wider study on the effects of pH on human hair properties, we investigated the time-dependence of pH-equilibration study across the acid and the basic pH-range, using appropriate pure solutions of hydrochloric acid and sodium hydroxide. The results show that pH-equilibration follows essentially equal 1st-order kinetics across the pH-range. The characteristic process time does not change significantly and is in the range of 2.5-5 h. The analysis enables to determine the equilibrium uptakes of H+- and OH- -ions. These follow the expected U-shaped path across the pH-range. For both acidic and alkaline conditions, data are well described by two very similar sorption isotherms of the Freundlich-type. In consequence, partition ratios for both ions are highest near neutrality (pH 7: >6000) and drop off strongly towards low and high pHs (<50). Hair is thus a very strong 'sink' for H+ and OH-. This observation fundamentally challenges traditional views of limited ion uptake, namely, in the mid-pH-range due to hindered diffusion. It also does not support considerations on special roles of certain pHs, specific groups of amino acids, or morphological components. Our analysis thus suggests that established views of the interaction of hair and pH need to be reconsidered, The Freundlich isotherm approach appears to provide a versatile tool to refine our understanding of the interactions of hair and possibly other keratinous materials (horn, nail, feathers) with acids and bases.

Toothpaste Abrasion and Abrasive Particle Content: Correlating High-Resolution Profilometric Analysis with Relative Dentin Abrasivity (RDA).

In this in vitro study, the influence of the concentration of abrasive particles on the abrasivity of toothpastes was investigated using laser scan profilometry on polymethyl methacrylate (PMMA) surfaces with the aim of providing an alternative method to developers for screening of new toothpaste formulations. PMMA plates were tested in a toothbrush simulator with distilled water and four model toothpastes with increasing content of hydrated silica (2.5, 5.0, 7.5, 10.0 wt%). The viscosity of the model toothpaste formulations was kept constant by means of varying the content of sodium carboxymethyl cellulose and water. The brushed surfaces were evaluated using laser scan profilometry at micrometer-scale resolutions, and the total volume of the introduced scratches was calculated along with the roughness parameters Ra, Rz and Rv. RDA measurements commissioned for the same toothpaste formulations were used to analyze the correlation between results obtained with the different methods. The same experimental procedure was applied to five commercially available toothpastes, and the results were evaluated against our model system. In addition, we characterize abrasive hydrated silica and discuss their effects on PMMA-sample surfaces. The results show that the abrasiveness of a model toothpaste increases with the weight percentage of hydrated silica. Increasing roughness parameter and volume loss values show good correlation with the likewise increasing corresponding RDA values for all model toothpastes, as well as commercial toothpastes without ingredients that can damage the used substrate PMMA. From our results, we deduce an abrasion classification that corresponds to the RDA classification established for marketed toothpastes.

Remineralization Strategies for Teeth with Molar Incisor Hypomineralization (MIH): A Literature Review.

Molar incisor hypomineralization (MIH) is a highly prevalent dental developmental disorder with a significant health burden for patients and high treatment needs, yet no comprehensive review article on all remineralization systems as a non-invasive treatment approach for MIH has been published. Typical characteristics of MIH-affected teeth are a lower mineral density and lower hardness compared to healthy teeth leading to sensitivity and loss of function. Thus, the use of formulations with calcium phosphates to remineralize MIH-affected teeth is reasonable. This review presents an up-to-date overview of remineralization studies focusing on active ingredients investigated for remineralization of MIH, i.e., casein phosphopeptide amorphous calcium phosphate (CPP-ACP), casein phosphopeptide amorphous calcium fluoride phosphate (CPP-ACFP), hydroxyapatite, calcium glycerophosphate, self-assembling peptide, and fluoride. Overall, 19 studies (in vitro, in situ, and in vivo) were found. Furthermore, an additional search for studies focusing on using toothpaste/dentifrices for MIH management resulted in six studies, where three studies were on remineralization and three on reduction of sensitivity. Overall, the studies analyzed in this review showed that MIH-affected teeth could be remineralized using calcium phosphate-based approaches. In conclusion, calcium phosphates like CPP-ACP, calcium glycerophosphate, and hydroxyapatite can be used to remineralize MIH-affected teeth. In addition to MIH-remineralization, CPP-ACP and hydroxyapatite also offer relief from MIH-associated tooth sensitivity.

Long-term efficacy and safety of 1% glycopyrronium bromide cream in patients with severe primary axillary hyperhidrosis: Results from a Phase 3b trial.

BACKGROUND: Primary axillary hyperhidrosis (PAHH) strongly affects the patient's quality of life. To date, topical treatment options are limited. One percent glycopyrronium bromide (GPB) showed promising efficacy and safety in a pivotal 4-week Phase 3a study. OBJECTIVES: To assess efficacy and safety of topical 1% GPB cream in patients with severe PAHH in a long-term study of 72 weeks versus baseline. METHODS: This was a long-term, open-label, Phase 3b trial for 72 weeks including 518 patients with severe PAHH. Patients were treated with 1% GPB cream once daily for 4 weeks, followed by a flexible dosing scheme (min. twice per week, max. once daily). Primary endpoint was the absolute change in sweat production from baseline to week 12. Further study endpoints included assessment of the severity of PAHH and the impact on quality of life. RESULTS: Total median sweat production decreased by 119.30 mg (-65.6%, both median) until week 12. Absolute change in sweat production from baseline to week 12 in logarithmic values was statistically significant (p < 0.0001). Patients' quality of life was improved at all study time points compared to baseline, as assessed by Hyperhidrosis Quality of Life Index and Dermatology Life Quality Index (p < 0.0001). Treatment was safe and locally well-tolerated with only few mild to moderate adverse drug reactions (ADRs). Dry mouth and application site erythema were the most common reported ADRs. CONCLUSIONS: Treatment with 1% GPB cream over 72 weeks significantly reduces sweat production and improves quality of life in patients with severe PAHH. One percent GPB cream is well-tolerated and provides an effective treatment option for long-term use in patients with severe PAHH.

Overview on Adjunct Ingredients Used in Hydroxyapatite-Based Oral Care Products.

Hydroxyapatite, Ca5(PO4)3(OH), is a biomimetic active ingredient, which is used in commercial oral care products such as toothpastes and mouthwashes worldwide. Clinical studies (in vivo) as well as in situ and in vitro studies have shown the preventive effects of hydroxyapatite in various field of oral care. In some products, hydroxyapatite is combined with other active ingredients, to achieve an additional antibacterial effect or to promote gum health. This review analyzes the efficacy of six selected natural and nature-inspired ingredients that are commonly used together with hydroxyapatite. These additional actives are either antibacterial (lactoferrin, xylitol, and zinc) or promote gum health (allantoin, bisabolol, and hyaluronic acid). A systematic literature search was performed, and all studies found on each ingredient were analyzed. In summary, all analyzed ingredients mentioned in this review are well described in scientific studies on their beneficial effect for oral health and can be used to expand the preventive effect of hydroxyapatite in oral care products.

On the Application of Calcium Phosphate Micro- and Nanoparticles as Food Additive.

The human body needs calcium and phosphate as essential nutrients to grow bones and teeth, but they are also necessary for many other biochemical purposes (e.g., the biosynthesis of phospholipids, adenosine triphosphate, ATP, or DNA). The use of solid calcium phosphate in particle form as a food additive is reviewed and discussed in terms of bioavailability and its safety after ingestion. The fact that all calcium phosphates, such as hydroxyapatite and tricalcium phosphate, are soluble in the acidic environment of the stomach, regardless of the particle size or phase, means that they are present as dissolved ions after passing through the stomach. These dissolved ions cannot be distinguished from a mixture of calcium and phosphate ions that were ingested separately, e.g., from cheese or milk together with soft drinks or meat. Milk, including human breast milk, is a natural source of calcium and phosphate in which calcium phosphate is present as nanoscopic clusters (nanoparticles) inside casein (protein) micelles. It is concluded that calcium phosphates are generally safe as food additives, also in baby formula.

Spatial probing of the properties of the human hair surface using Wilhelmy force profiles.

The natural surface of human hair (epicuticle) consists of a bilayer of heavily cross-linked proteins toward the individual cuticle cell inside combined with a monomolecular, hydrophobic layer of mixed fatty acids to the outside (F-layer), which is generally assumed to be homogeneous. Wetting force profiles along segments of hair from female test persons with lengths equivalent to about 1 month of growth (approximately 10 mm) are presented. In a multistep analysis, applying curve smoothing as well as Fourier and principal components analysis, for hair lengths comprising daily and weekly growth (2 mm) pronounced systematic changes are observed in the profiles, which show that the wettability curves are nonstochastic in nature and that hair exhibits a strongly nonhomogeneous surface. Specifically, a compound daily rhythm is observed for wettability, which through its typical bimodality can be linked to continuous changes of the hair surface during wake and sleep phases. The data set furthermore suggests systematic monthly changes, which may be related to the menstrual cycle. In consequence, the results not only provide proof for the inhomogeneity of the immediate hair surface but also lead to the hypothesis that it preserves a rather detailed and long-term, individual chronobiological record, through a specific, spatially modulated distribution of hydrophobic (lipids) and hydrophilic (proteins) regions, "written" by the composition of the cell membrane of the cuticle cell prior to apoptosis.