Strontium for use in the treatment of diabetes, alcohol use disorder, obesity, and inducing cosmetic weight loss

Abstract

The present invention relates to strontium for use in the treatment or prevention of diabetes and / or obesity or alcohol use disorder by administering between 20-70 mg strontium daily via mucosal administration in an oral care composition to diabetes patients, including diabetes with obesity and comorbid gum diseases. The invention further relates to use of strontium in a method of cosmetic weight loss and / or to reduce alcohol desire.

Description

[0001] DESCRIPTION

[0002] Strontium for use in the treatment of diabetes, alcohol use disorder, obesity, and inducing cosmetic weight loss.

[0003] FIELD

[0004] The present invention relates to a composition for treating or reducing the impact of diabetes. The invention also relates to a composition for treating or reducing the impact of obesity. Additionally, it concerns a composition for cosmetic use in inducing weight loss. Further, it relates to treating alcohol use disorder. More specifically, the invention involves the administration of strontium to regulate blood glucose levels, and / or reducing appetite, and / or alcohol desire.

[0005] BACKGROUND

[0006] Diabetes is a significant public health concern, which contributes to metabolic disorders, cardiovascular diseases, and reduced quality of life. Current treatment approaches for diabetes focus on improving insulin sensitivity, glucose regulation, and pancreatic function. However, many existing treatments have side effects or limited efficacy, highlighting the need for improved therapeutic alternatives. Given that excessive insulin levels (hyperinsulinemia) are associated with insulin resistance, metabolic dysregulation, and the tendency to require progressively higher doses over time and weight gain, there is an increasing need for alternative strategies to help regulate blood glucose while reducing dependency on exogenous insulin or excessive insulin production.

[0007] Prediabetes is a condition in which blood sugar levels are higher than normal but not yet high enough to be classified as type 2 diabetes. It is often referred to as a precursor to type 2 diabetes because it indicates that the body's ability to regulate blood sugar naturally is starting to decline.

[0008] Prediabetes will often evolve into type 2 diabetes if left untreated. Symptoms such as increased thirst, frequent urination, unusual fatigue, and recurrent infections can be signs that an individual is beginning to develop diabetes. Other risk factors include weight gain, physical inactivity, and a diet high in fat.

[0009] Lifestyle modifications, such as maintaining a healthy diet and engaging in regular physical activity, are crucial in preventing the onset of diabetes. However, low patient compliance remains a significant challenge, thus highlighting the need for alternative preventive methods.Today, diabetes patients may be treated with rapid-acting insulin like insulin aspart (such as the medicinal product NovoRapid) that is used to treat diabetes by mimicking the body's natural insulin response after meals. It binds to insulin receptors on muscle, fat, and liver cells, enhancing glucose uptake and inhibiting glucose production in the liver.

[0010] Another available treatment is long-acting insulin like insulin glargine (such as the medicinal product Lantus) that provides stable and prolonged blood sugar control. It has a slow onset and releases insulin steadily over an extended period, mimicking the body's basal insulin secretion.

[0011] Diabetes can also be managed with metformin, which lowers blood sugar by reducing hepatic glucose production, enhancing insulin sensitivity, and decreasing intestinal glucose absorption. It primarily acts on the liver to inhibit gluconeogenesis, improving glucose control without directly stimulating insulin secretion.

[0012] Diabetes and obesity are often interconnected, as obesity is a known risk factor for insulin resistance and type 2 diabetes. However, obesity can also occur independently of diabetes and vice versa.

[0013] Obesity is also a significant public health concern which contributes to metabolic disorders, cardiovascular diseases, and reduced quality of life.

[0014] Diabetes and gum diseases are also often interconnected. It is known that oral care compositions comprising strontium is effective against the development of biofilm, thereby reducing the incidence of periodontitis and that the treatment can avoid consequences such as loss of teeth, ligament destruction, jawbone destruction, and receding gums.

[0015] Obesity is a condition where the amount of fat in the body has increased to a level that affects health. Since there are no simple methods to accurately measure body fat mass, body mass index (BMI) is commonly used as an indicator. BMI is calculated as body weight divided by height squared (kg / m2). Different countries define overweight in various ways, for example in Denmark, a BMI between 25 and 30 kg / m2is classified as overweight, while a BMI above 30 kg / m2indicates obesity or severe overweight. Denmark further defines the normal weight range as a BMI between 18.5 and 25 kg / m2, whereas it was previously set between 20 and 25 kg / m2. Obesity is categorized into different BMI groups based on the associated health risks, with a BMI above 30 kg / m2referred to as severe overweight or obese.Treating obesity typically involves caloric restriction, increased physical activity, and appetite regulation. However, low patient compliance remains a significant challenge. Other approaches include GLP-1 receptor agonists, such as semaglutide (Ozempic, Wegovy), which mimic the GLP-1 hormone to stimulate insulin secretion, suppress glucagon release, slow gastric emptying, and regulate appetite, ultimately aiding in weight loss.

[0016] Even if a patient's BMI is below the obesity threshold (>30), weight management can still be relevant for cosmetic reasons. The same strategies used to treat obesity can also be applied to induce cosmetic weight loss and typically include caloric restriction, increased physical activity, appetite regulation, and GLP-1 receptor agonists (such as Wegovy).

[0017] Strontium has been used as a drug to promote bone growth and increase bone density and is also utilized in the cosmetic industry in skincare and oral care formulations for its soothing and anti-inflammatory properties. Additionally, strontium has been proposed for treatment of cartilage and bone disorder as disclosed in EP1768748B2. Strontium has also been suggested for the treatment of oral diseases due to its antibacterial properties and biofilm-disrupting capabilities as disclosed in Patent No. EP2023 / 058235. This patent further suggests that strontium based oral care compositions may provide inhibition, reduction, treatment, or prophylaxis of diseases relating to gum disease including diabetes, in particular Type-ll diabetes; Alzheimer disease; cardiovascular diseases, in particular stroke, heart attack, and / or heart failure; premature low-weight babies; lung infections, like bronchitis; pneumonia; or emphysema.

[0018] As presented herein, it has been unexpectedly discovered that administering 20 mg to 70 mg of strontium via mucosal administration in an oral care composition to a type 2 diabetic subject lowers resting blood glucose levels after a night's sleep and reduces blood glucose fluctuations. As a result, type 2 diabetic subjects experienced a more than 50% reduction in the required daily insulin administration. After prolonged period of administration, one subject experienced a 80% - 90% reduction in daily insulin administration.Furthermore, subjects reported that the administration of strontium significantly reduced their appetite and cravings for alcohol, leading to substantial weight loss of more than 20% during a 2-year period.

[0019] SUMMARY

[0020] An object of the present invention is to provide strontium, which regulates blood glucose levels, for the prevention and / or treatment of diabetes.

[0021] In particular, the invention aims to enhance metabolic control in individuals with prediabetes, insulin resistance, or diabetes, and potentially reducing the risk of developing the disease.

[0022] Another object of the present invention is to provide strontium to regulate appetite and / or decrease cravings for alcohol thereby supporting weight loss in obese individuals or supporting cosmetic weight loss.

[0023] Another object of the present invention is to provide strontium to treat alcohol use disorder.

[0024] Another object of the present invention is to provide strontium to reduce alcohol desire.

[0025] Accordingly, the present invention relates in a first aspect to strontium, or a pharmaceutically acceptable salt thereof for use in the treatment or prevention of diabetes and / or obesity or alcohol use disorder, wherein the strontium is administered at a dose of about 20 mg to about 70 mg per day via mucosal administration in an oral care composition e.g. a toothpaste or a mouthwash.

[0026] In a second aspect, the present invention relates strontium, or a pharmaceutically acceptable salt thereof, for use in a method of cosmetic weight reduction, and for use in a method to reduce alcohol desire, wherein the strontium is administered at a dose of about 20 mg to about 70 mg per day via mucosal administration in an oral care composition e.g. a toothpaste or a mouthwash.

[0027] BRIEF DESCRIPTION OF DRAWINGS

[0028] Figure 1 presents graphs illustrating (A) insulin dosage (doses), (B) fasting blood glucose levels (mmol / L), (C) metformin intake (mg), and (D) Body weight (kg), in a type 2 diabetic and obese subject, both before treatment and over a two-month period following one year of treatment. FG is indicating fasting glucose in mmol / lFigure 2 Presents a table showing resting glucose levels in mmol / L before and after treatment with strontium, * is indicating Below normal values, ** is indicating Normal values while *** is indicating Above normal values.

[0029] Figure 3 presents a graphs showing fasting blood glucose levels in mmol / L measured in the morning disclosing monthly average measurements in year 1 wherein no strontium was administered and year 2 wherein strontium was administered at 70 mg per day via mucosal administration in a toothpaste.

[0030] Figure 4 presents a graphs showing fasting blood glucose levels in mmol / L measured in the evening disclosing monthly average measurements in year 1 wherein no strontium was administered and year 2 wherein strontium was administered at 70 mg per day via mucosal administration in a toothpaste.

[0031] DETAILED DESCRIPTION OF THE INVENTION

[0032] As disclosed herein, the administration of a daily strontium dose reduces blood glucose and decreases the need for insulin administration in diabetes treatment. Accordingly, strontium for use in the treatment of diabetes and / or prevention of the disease is disclosed. Furthermore, the daily administration of strontium has an appetite-regulating effect and decreases the desire of alcohol which results in an observed weight loss. These surprising findings support that administration of strontium can help treat obesity and provide a cosmetic weight reduction.

[0033] Thus, one aspect of the present invention is strontium, or a pharmaceutically acceptable salt thereof for use in the treatment or prevention of diabetes and / or obesity or alcohol use disorder wherein the strontium is administered at a dose of about 20 mg to about 70 mg per day via mucosal administration in an oral care composition.

[0034] One embodiment of the present invention accordingly relates to strontium, or a pharmaceutically acceptable salt thereof for use in the treatment or prevention of diabetes wherein strontium is administrated at a dose of about 20 mg to about 70 mg per day via mucosal administration in an oral care composition.Another embodiment of the present invention accordingly relates to strontium, or a pharmaceutically acceptable salt thereof for use in the treatment or prevention of obesity wherein the strontium is administrated at a dose of about 20 mg to about 70 mg per day via mucosal administration in an oral care composition.

[0035] Another embodiment of the present invention is strontium, or a pharmaceutically acceptable salt thereof for use in the treatment or prevention of diabetes and / or obesity or alcohol use disorder wherein the strontium is administrated at a dose of about 20 mg to about 70 mg per day via mucosal administration in an oral care composition.

[0036] When strontium, or a pharmaceutically acceptable salt thereof is administered as a toothpaste formulation, the formulation should comprise between 2%(w / w) -10%(w / w) strontium, or a pharmaceutically acceptable salt thereof.

[0037] Toothpaste containing either 2%, 3.5% or 10% strontium by total weight was used for testing. Depending on whether an electric or a manual toothbrush was used, the administered dosage was either 1 g for an electric toothbrush or 2 g for a manual toothbrush.

[0038] This corresponds to a daily dose ranging from 10 mg when brushing once a day with an electric toothbrush, up to 300 mg when brushing three times a day with a manual toothbrush.

[0039] As disclosed herein mucosal administration of 35 mg of strontium twice a day was found to reduce blood glucose, decrease the need for diabetes treatment, and support weight loss. Also, signs of gingivitis and periodontitis were moreover completely eliminated.

[0040] Thus, the strontium is administered to the subject in need thereof by mucosal administration.

[0041] The reduction in blood glucose, weight loss, reduced gingivitis and periodontitis and reduced desire for alcohol was observed by a diabetic patient with obesity and comorbid gum diseases. The initiation of these effects was observed already after 30 days of brushing teeth twice a day with a toothpaste comprising 3.5% strontium corresponding to a daily dose of 70 mg.In one embodiment, strontium, or a pharmaceutically acceptable salt thereof for use in the treatment or prevention of diabetes and / or obesity wherein the strontium is administered at a dose of 20 mg to 70 mg per day, preferably 70 mg per day via mucosal administration in an oral care composition is administered to diabetic patients with obesity.

[0042] In another embodiment, strontium, or a pharmaceutically acceptable salt thereof for use in the treatment or prevention of diabetes and / or obesity wherein the strontium is administered at a dose of 20 mg to 70 mg per day, preferably 70 mg per day via mucosal administration in an oral care composition is administered to diabetic patients with obesity and comorbid gum diseases.

[0043] Strontium, or a pharmaceutically acceptable salt thereof is administered in an oral care comprising of one or more pharmaceutically acceptable excipients.

[0044] Further seen herein, it has been found that mucosal delivery is an effective method of administering strontium.

[0045] Thus, strontium, or a pharmaceutically acceptable salt, is administered in an oral care composition e.g. a toothpaste or a mouthwash.

[0046] In oner embodiment strontium is dissolved in a solvent selected from: alcohols, sugar alcohols, water-based solvents, or mixtures thereof.

[0047] Thus, the present invention relates to an oral care composition comprising a carrier material, at least one strontium salt, a sugar alcohol, wherein the composition comprises a moisture content above 15% (w / w).

[0048] The oral care composition may comprise a carrier material, at least one strontium salt, wherein the composition comprises a moisture content above 50% (w / w).

[0049] Preferably, the oral care composition according to the present invention comprising a carrier material, at least one strontium salt, wherein the composition comprises a moisture content above 50% (w / w), further comprising a sugar alcohol.Sugar alcohols may be organic compounds, typically derived from sugars, containing one hydroxyl group (-OH) attached to each carbon atom in the molecule. They may traditionally be white, water-soluble solids and may occur naturally in nature or be produced industrially by hydrogenation of sugars. Since sugar alcohols contain multiple OH-groups, sugar alcohols may be classified as polyols.

[0050] Sugar alcohols are used widely in the food industry and pharma industry, e.g. as thickeners and / or sweeteners and are well known to the skilled person. A sugar alcohol could for example be xylitol.

[0051] The carrier material may be a material capable of dissolving and / or suspending in the at least one strontium salt and the sugar alcohol. Preferably, the carrier material may be water.

[0052] The oral care composition may comprise a moisture content above 20% (w / w), e.g. above 30% (w / w), such as above 40% (w / w), e.g. above 50% (w / w), such as above 60% (w / w), e.g. above 70% (w / w), such as above 75% (w / w), e.g. above 80% (w / w), such as above 85% (w / w) , e.g. above 90% (w / w), such as above 92% (w / w), e.g. in the range of 20-98% (w / w), such as in the range of 40-95% (w / w), e.g. in the range of 60-92% (w / w), such as in the range of 75-90% (w / w), e.g. in the range of 80-85% (w / w).

[0053] Preferably, the content of a sugar alcohol, in particular xylitol, may be in the range of 0.05-20% (w / w), such as in the range of 0.1-15% (w / w), e.g. in the range of 0.5-10% (w / w), such as in the range of 1-7.5% (w / w), e.g. in the range of 1.5-5% (w / w), such as in the range of 2-4.5% (w / w), e.g. in the range of 3-4% (w / w).

[0054] The oral care composition may further comprise a sweetener.

[0055] The oral care composition may further comprise a preservative agent and / or a flavoring agent.

[0056] Even though some of the other ingredients of the oral care composition may comprise a preservative activity of the oral care composition, a preservative agent may be added to the oral care composition.A preservative agent may be added to the oral care composition and may be selected from sodium benzoate, potassium sorbate, benzoic acid, or a combination hereof.

[0057] Even though the mentioned preservative agents may be the preferred preservative agents, the skilled person would know other relevant preservative agents that may be used in combination or alone in an oral care composition according to the present invention.

[0058] The oral care composition may comprise less than 10% (w / w) alcohol, such as less than 7.5% (w / w), e.g. less than 5% (w / w), such as less than 2.5% (w / w), e.g. less than 1% (w / w). Preferably, the oral care composition according to the present invention comprises no alcohol.

[0059] The oral care composition may further comprise one or more fluoride compounds. Preferably, at least one strontium salt may include at least one water soluble strontium salt. Even more preferably, at least one water soluble strontium salt may be strontium chloride.

[0060] The amount of strontium obtained from a specific amount of strontium salt may depend on the molecular weight of the compound, relative to the number of strontium molecules therein, thus a salt with low molecular weight per strontium molecule may be preferred.

[0061] This may be expressed as the effective ratio (ER) of the salt. The effective ratio (ER) may be defined as, ER= (strontium (mg)) / (strontium salt (mg))

[0062] The higher effective ratio (ER) the smaller amount of salt is required for obtaining the desired effect. As a relatively large amount of the active ingredient is required, a strontium salt with a high effective ratio is preferred.

[0063] In the present invention, it may be preferred that the ER of the strontium salt present in the oral care composition may be more than 0.40, or more than 0.45 or 0.50, such as more than 0.53 such as more than 0.55, such as in the range of 0.40-0.70, e.g. in the range of 0.45-0.65, such as in the range of 0.50-0.60, e.g. in the range of 0.55-The present invention may comprise of at least one strontium salt and at least one water-soluble strontium salt.

[0064] Preferably, the at least one water-soluble strontium salt present in the composition according to the present invention has a solubility in water at room temperature of at least 25 g / L, such as at least 50 g / L, e.g. at least 75 g / L, such as at least 100 g / L, e.g. at least 150 g / L, such as at least 200 g / L, e.g. at least 250 g / L, such as at least 300 g / L, e.g. at least 350 g / L, such as at least 400 g / L, e.g. at least 450 g / L, such as at least 500 g / L, e.g. at least 525 g / L, such as in the range of 25-750 g / L, e.g. in the range of 100-700 g / L, such as in the range of 200-650 g / L, e.g. in the range of SOO-625 g / L, such as in the range of 400-600 g / L, e.g. in the range of 500-550 g / L.

[0065] Preferably, the one or more water soluble strontium salt may be selected from the group consisting of strontium chloride, strontium bromide, strontium nitrate, strontium hydroxide, strontium oxide, strontium acetate, strontium glutamate, strontium aspartate, strontium malonate, strontium pyruvate, strontium alpha-ketoglutarate, strontium maleate, strontium succinate, strontium fumarate, strontium ascorbate, strontium tartate, strontium glutarate, strontium methanesulfonate, strontium benzenesulfonate, strontium sulphide, and a combination hereof. More preferably, the at least one water soluble strontium salt may be strontium chloride.

[0066] Thus, preferably the at least one strontium salt may be strontium chloride.

[0067] The oral care composition according to the present invention wherein the strontium chloride may be selected from the group consisting of SrCh, SrCh-2- H2O, SrCl2'6- H2O, or a combination hereof.

[0068] Preferably, the at least one strontium salt, in particular strontium chloride, may be anhydrous, specifically strontium chloride may be strontium chloride anhydrous or strontium chloride hexahydrate.

[0069] The oral care composition may include at least one strontium salt and at least one water soluble strontium salt, and preferably, the at least one water soluble strontium salt is strontium chloride.The content of the at least one strontium salt in the oral care composition according to the present invention may be dependent on e.g. the formulation of the oral care composition, the condition of the mouth of the subject to be treated, the condition of the subject to be treated, and / or the age of the subject to be treated, in particular the age of the subject to be treated.

[0070] Preferably, the oral care composition comprises in the range of 0.5-15% (w / w) of the at least one strontium salt (in particular the strontium salt may be strontium chloride), such as in the range of 0.6-14% (w / w) of the at least one strontium salt, e.g. in the range of 0.7-13% (w / w) of the at least one strontium salt, such as in the range of 0.8-12% (w / w) of the at least one strontium salt, e.g. in the range of 0.9-11% (w / w) of the at least one strontium salt, such as in the range of 1.0-10% (w / w) of the at least one strontium salt, e.g. in the range of 1.25-9% (w / w) of the at least one strontium salt, such as in the range of 1.5-8% (w / w) of the at least one strontium salt, e.g. in the range of 1.75-7% (w / w) of the at least one strontium salt, such as in the range of 2-6% (w / w) of the at least one strontium salt, e.g. in the range of 2.5-5% (w / w) of the at least one strontium salt, such as in the range of 3-4% (w / w) of the at least one strontium salt, e.g. about 3.5% (w / w).

[0071] The oral care composition may preferably comprise in the range of 0.25-8% (w / w) of strontium ions in the oral care composition, such as in the range of 0.5-5% (w / w), e.g. in the range of 1.0-4% (w / w), such as in the range of 1.5-3% (w / w), e.g. in the range of 1.75-2.5% (w / w), such as about 2.0% (w / w).

[0072] The oral care composition may include at least one strontium salt, or the oral care composition may comprise a water insoluble strontium salt or a combination of a water- soluble strontium salt and a water insoluble strontium salt.

[0073] Preferably, the water insoluble strontium salt may be selected from the group consisting of strontium carbonate and strontium sulphate. Even more preferably, the water insoluble strontium salt may be strontium carbonate.The oral care composition may comprise at least 45% (w / w) strontium in the form of a water-soluble strontium salt, such as at least 50% (w / w) strontium in the form of a water-soluble strontium salt, e.g. at least 60% (w / w) strontium in the form of a water-soluble strontium salt, such as at least 70% (w / w) strontium in the form of a water-soluble strontium salt, e.g. at least 80% (w / w) strontium in the form of a water-soluble strontium salt, such as at least 90% (w / w) strontium in the form of a water-soluble strontium salt, e.g. at least 95% (w / w) strontium in the form of a water-soluble strontium salt, such as at least 98% (w / w) strontium in the form of a water-soluble strontium salt, e.g. at least 99% (w / w) strontium in the form of a water-soluble strontium salt, such as about 100% (w / w) strontium in the form of a water-soluble strontium salt, e.g. in the range of 45-100 % of strontium in the form of a water-soluble strontium salt, such as in the range of 60-99 % strontium in the form of a water-soluble strontium salt, e.g. in the range of 75-98 % strontium in the form of a water-soluble strontium salt, such as in the range of 85-95 % strontium in the form of a water soluble strontium salt.

[0074] The oral care composition may be a mouthwash composition.

[0075] Preferably, the oral care composition, or the mouthwash, comprises a carrier material, preferably water. An active ingredient, e.g. an API, provided by at least one strontium salt, preferably strontium chloride; a pH regulator / sugar substitute, preferably xylitol; a sweetener, preferably stevia; a preservative, preferably sodium benzoate; and flavouring / aroma agent, preferably Mentha Piperita Oil and / or Mentha Spicata flower Extract.

[0076] Preferably the concentration of strontium chloride in the oral care composition was as described above, preferably about 3.5% (on a weight-by-weight basis - (w / w)) of the oral care composition and the concentration of xylitol was as described above, preferably, about 3% (on a weight-by-weight basis - (w / w)). The oral composition according to the present invention may be provided as a gel, mouthwash, toothpaste, or a liquid.The oral composition according to the present invention may be formulated into a gel. Preferably, the gel may be applied to the teeth and / or to the gums. The gel may be rubbed onto the teeth and / or into the gums.

[0077] In a preferred embodiment the gel will contain 2-10 % (w / w) strontium, or a pharmaceutically acceptable salt thereof, 2%, 3.5% or 10 % (w / w) strontium.

[0078] The oral composition according to the present invention may be a liquid, which is held in the mouth passively or swilled around the mouth by contraction of the perioral muscles and / or movement of the head, and may be gargled, where the head is tilted back and the liquid bubbled at the back of the mouth.

[0079] Preferably, the mouthwash comprises a pH value in the range of pH 5-8, such as in the range of pH 6-7.5, e.g. about pH 7.

[0080] The oral composition may be a pharmaceutical product comprising a moisture content above 20% (w / w), e.g. above 30% (w / w), such as above 40% (w / w), e.g. above 50% (w / w), such as above 60% (w / w), e.g. above 70% (w / w), such as above 75% (w / w), e.g. above 80% (w / w), such as above 85% (w / w) , e.g. above 90% (w / w), such as above 92% (w / w), e.g. in the range of 20-98% (w / w), such as in the range of 40- 95% (w / w), e.g. in the range of 60-92% (w / w), such as in the range of 75-90% (w / w), e.g. in the range of 80-85% (w / w).

[0081] Preferably, the pharmaceutical product may be an oral composition according to the present invention.

[0082] As seen herein, the mucosal administration of strontium twice a day effect blood glucose and regulating appetite and desire for alcohol, which supports that administration of strontium in a dose of 20 mg to 70 mg per day will also providea cosmetic weight loss in subjects that are not necessarily suffering from diabetes and / or medicinal obesity.

[0083] Thus, in a second aspect the present invention relates to strontium, or a pharmaceutically acceptable salt thereof for use in a method of cosmetic weight reduction wherein the strontium is administered at a dose of 20 mg to 70 mg per day in an oral care composition e.g. a toothpaste or a mouthwash.

[0084] In a preferred embodiment of this aspect, strontium, or a pharmaceutically acceptable salt thereof is for use in a method of cosmetic weight reduction wherein the strontium is administered at a dose of 20 mg to 70 mg per day in an oral care composition, wherein said oral care composition is a toothpaste formulation comprising the following ingredients:

[0085] 76-92 % (w / w) demineralized water, 3-6 % (w / w) xylitol, 2-10 % (w / w) strontium chloride, 0.1-1 % (w / w) stevia, 0.01-0.5 % (w / w) sodium benzoate, 0.01-0.5 % (w / w) menthae piperitae, 0.01-0.5 % (w / w) spearmint oil and 3-6 % (w / w) metolose or methylcellulose, wherein the sum of the ingredients is 100 % (w / w).

[0086] In another embodiment, strontium, or a pharmaceutically acceptable salt thereof is for use in a method of cosmetic weight reduction wherein the strontium is administered at a dose of 20 mg to 70 mg per day in an oral care composition, wherein said oral care composition is wherein said oral care composition is a mouthwash formulation comprising the following ingredients:

[0087] Aqua, xylitol, strontium chloride, stevia, sodium benzoate, mentha piperita oil, mentha spicata flower extract.

[0088] It can further be seen herein that the administration of 35 mg of strontium twice a day reduces blood glucose and provides weight loss. It is assumed that the effect observed in a type 2 diabetic subject would be similar in a non-diabetic subject.The invention will now be described in further detail in the following examples.

[0089] EXAMPLES

[0090] Example 1 - in vivo testing of strontium in diabetes patient with obesity

[0091] A male subject, aged 79, with type 2 diabetes (fasting glucose levels after a night's sleep ranging from 8 to 12 mmol / L, as shown in Figure 1B) and obesity (weight: 106 kg, BMI: 34.2) was administered strontium by brushing his teeth twice daily with approximately 1 g of toothpaste containing 3.5% strontium corresponding to a daily administration of 70 mg of strontium.

[0092] After one year of treatment, blood glucose levels were measured every morning after a night's sleep for two months using Accu-check aviva. The toothpaste applied had the composition: 86.9% (w / w) demineralized water, 4.43% (w / w) xylitol, 3.45% (w / w) strontium chloride, 0.236% (w / w) stevia, 0.0493% sodium benzoate, 0.0443 (w / w) menthae piperitae, 0.0236% (w / w) spearmint oil and 4.43% (w / w) metolose.

[0093] After two months of treatment, the subject observed decreased resting blood glucose levels, fewer fluctuations in blood glucose, and a reduced need for diabetes medication. After one year of treatment, his fasting glucose levels shifted to the values shown in figure 1B (ranging from 4 to 8.8 mmol / L). This reduction resulted in a significant decrease in the required dosage of diabetes medication.

[0094] Lantus usage decreased from approximately 44 to 14 doses per day, while Novoflex was reduced from approximately 40 to 18 doses per day. Additionally, metformin intake, initially 750 mg twice daily, was eliminated entirely (figure 1).

[0095] The subject also experienced appetite regulation and a reduced desire for alcohol, leading to a sustained decrease in food and alcohol intake. Over the course of one year, this effect contributed to a measurable weight loss of approximately 16 kg (figure 1).

[0096] One dose of Lantus equals 1 mL, which contains 100 E of insulin glargine.

[0097] One dose of Novorapid equals 1 mL, which contains 100 E of insulin aspart.Example 2 - in vivo testing of strontium in diabetes patient with obesitv and comorbid oral diseases

[0098] A male subject, aged 80, with type 2 diabetes and obesity (weight: 106 kg, BMI: 34.2) measured his blood glucose levels morning and evening regularly Accu-check aviva since his diabetes diagnosis. At the time point when the present test was made, he had suffered from diagnosed diabetes for XXX years. His medicinal diabetes treatment consisted of daily administration of approximately 44 Lantus doses per day, and approximately 40 NovoRapid doses per day. Additionally, he was treated with metformin 750 mg twice daily.

[0099] One dose of Lantus equals 1 mL, which contains 100 E of insulin glargine.

[0100] One dose of NovoRapid equals 1 mL, which contains 100 E of insulin aspart.

[0101] Figure 3 shows the blood glucose levels measured morning and evening, respectively, for the one-year period preceding initiation of treatment with strontium (Year 1). During Year 1, the fasting glucose levels measured in the morning ranged from approximately 6 to approximately 10 mmol / L, with an average of 8.25 mmol / L (Figure 3, dashed lines). In the evening, the fasting glucose levels ranged from approximately 12 to approximately 13 mmol / L, with an average of 12.7 mmol / L (Figure 4, dashed lines).

[0102] The following year (Year 2) the subject started additional treatment with strontium. Strontium was administered by brushing his teeth twice daily with approximately 1 g of toothpaste containing 3.5% strontium corresponding to a daily administration of 70 mg of strontium. No rinsing was performed after toothbrushing.

[0103] The toothpaste applied had the composition: 86.9% (w / w) demineralized water, 4.43% (w / w) xylitol, 3.45% (w / w) strontium chloride, 0.236% (w / w) stevia, 0.0493% sodium benzoate, 0.0443 (w / w) menthae piperitae, 0.0236% (w / w) spearmint oil and 4.43% (w / w) methylcellulose.

[0104] The subject’s physical activity level remained unchanged, and both the quantity and type of food intake also remained unchanged during Year 1 and Year 2.

[0105] During Year 2, fasting blood glucose levels were measured every morning and every evening using Accu-check aviva. During Year 2, the fasting glucose levels measuredin the morning ranged from approximately 5 to just below 8 mmol / L, with an average of 5.9 mmol / L (Figure 3, solid lines). In the evening, the fasting glucose levels ranged from approximately 10 to approximately 12 mmol / L, with an average of 10.5 mmol / L (Figure 4, solid lines).

[0106] Accordingly, the fasting blood glucose level measured in the morning decreased on average 28% from Year 1 to Year 2 and the decrease was observed already after 1 month of initiating mucosal strontium administration. Also, the fasting blood glucose level measured in the evening decreased on average 17% from Year 1 to Year 2 and this decrease was also observed already after 1 month of initiating mucosal strontium administration.

[0107] This reduction resulted in a significant decrease in the required dosage of diabetes medication. The subjects need to administer Lantus for the treatment of diabetes decreased by 63% during Year 2. The subjects need to administer and NovoRapid for treatment of diabetes was reduced by 30%. Additionally, metformin intake, initially 750 mg twice daily, was eliminated entirely.

[0108] The subject also experienced appetite regulation and a reduced desire for alcohol, leading to a sustained decrease in food and alcohol intake. Over the course of one year, this effect contributed to a significant weight loss of approximately 16 kg. Moreover, during Year 2, the subject’s intake of alcohol significantly decreased due to loss of desire for alcohol. Additionally, the subject experienced that his previous symptoms of periodontitis and gingivitis disappeared completely.

[0109] Example 3 - in vivo testing of strontium in diabetes patient

[0110] The same male subject, with type 2 diabetes as described in Example 2 (weight: 106 kg, BMI: 34.2) continued to measurehis blood glucose levels in the morning with Accu-check aviva during a two-month period (i.e. the beginning of Year 3). At the point in time when these measurements were made, he had accordingly suffered from diagnosed diabetes for 30 years. The subject’s physical activity level remained unchanged, and both the quantity and type of food intake also remained unchanged during Year 1 and Year 2.His mec licinal di abetes tre< atment c f Lanti JS and N ovoRapid is shown in the be low table. Tt le requir ement for netformi n was io longer present.

[0111] Morning NovoRapid Lantus Morning NovoRapid Lantus Jan. Feb.

[0112] 1 6.4 0 0 1 6 8 10 i 2 7.1 0 10 2 4.5 0 10 i 3 4.5 0 10 3 4.4 0 0 4 5.9 0 10 4 7 0 0 i 5 4.1 0 0 5 7 0 0 i 6 6.7 8 10 6 6.9 8 10 i 7 5.2 8 10 7 5 0 0 : 8 4.9 0 0 8 7.5 8 10 i 9 7.8 0 0 9 6.7 0 0 i 10 5.4 8 10 10 6.6 0 0 11 6.1 0 10 11 5.9 0 0 i 12 5.6 0 10 12 6.7 8 10 i 13 5.5 0 5 13 6.4 8 10 14 6.9 8 10 14 5.9 0 0 15 8.5 5 10 15 7.2 0 0 16 5.9 5 10 16 6.6 0 8 17 7.5 8 10 17 6.7 5 8 : 18 6.4 0 0 18 4.1 5 10 19 5.5 5 0 19 4.8 5 10 i 20 5.8 8 10 20 4.7 0 0 i 21 7 8 10 21 4.8 0 0 i 22 6 0 0 22 7.4 0 0 i 23 5 0 10 23 7.4 8 5 i 24 6.4 0 0 24 5 0 0 i 25 7.7 0 10 25 7 0 0 i 26 5.8 8 12 26 6.4 0 0 i 27 4.6 7 10 27 7.2 8 10 : 28 4.4 0 10 28 7.3 8 10 i 29 4.7 0 0

[0113] i 30 5.7 8 10

[0114] i 31 5.2 8 10

[0115] Tot. 184.2 102 217 Tot. 173.1 79 121

[0116]

[0117] ; Average 5.9 3.3 7 Average 6.2 2.8 4.3

[0118] The fasting blood glucose level measured in the morning was for the first two month of Year 3 approximately the same as the average observed in Year 2 (cf. Example 2). However, the need for medicinal diabetes treatment with NovoRapid and Lantus wasreduced even further in the first two month of Year 3. Before strontium administration started (Year 1 , Example 1), the patient required daily administration of approximately 44 Lantus doses per day, and approximately 40 NovoRapid doses per day. Additionally, he was treated with metformin 750 mg twice daily. During the first two months of Year 3, the patient required daily administration of approximately 7 Lantus doses per day, and approximately 4 NovoRapid doses per day. There was no longer a need for treatment with metformin. Accordingly, the need for medicinal treatment was reduced by approximately 84% (Lantus), and by 90% (NovoRapid) and 100% (metformin). Such a great reduction in required diabetes treatment was completely unforeseen and is extremely surprising and highlights the significant effect of the daily mucosal administration of 70 mg strontium to diabetes patients.

[0119] At the beginning of year 3, the weight of the patient was 88 kg and the BMI was 28.4. The weight from year 1 (106 kg, BMI 34.1) had accordingly dropped 18 kg corresponding to a weight reduction of more than 20%.

Claims

CLAIMS:1 . Strontium, or a pharmaceutically acceptable salt thereof for use in the treatment or prevention of diabetes and / or obesity or alcohol use disorder wherein the strontium is administered at a dose of 20 mg to 70 mg per day via mucosal administration in an oral care composition e.g. a toothpaste or a mouthwash.

2. Strontium for use according to claim 1, wherein said oral care composition is administered to a diabetic patient with obesity.

3. Strontium for use according to claim 1, wherein said oral care composition is administered to a diabetic patient with obesity and comorbid gum disease.

4. Strontium, or a pharmaceutically acceptable salt thereof for use according to any one of the preceding claims, wherein the strontium is dissolved in a solvent selected from: alcohols, sugar alcohols, water-based solvents, or mixtures thereof.

5. Strontium, or a pharmaceutically acceptable salt thereof for use according to claim 1, wherein said oral care composition is a toothpaste formulation comprising the following ingredients:76-92 % (w / w) demineralized water, 3-6 % (w / w) xylitol, 2-10 % (w / w) strontium chloride, 0.1-1 % (w / w) stevia, 0.01-0.5 % (w / w) sodium benzoate, 0.01-0.5 % (w / w) menthae piperitae, 0.01-0.5 % (w / w) spearmint oil and 3-6 % (w / w) metolose or methylcellulose, wherein the sum of the ingredients is 100 % (w / w).

6. Strontium, or a pharmaceutically acceptable salt thereof for use according to claim 1, wherein said oral care composition is a mouthwash formulation comprising the following ingredients:Aqua, xylitol, strontium chloride, stevia, sodium benzoate, mentha piperita oil, mentha spicata flower extract.

7. Strontium, or a pharmaceutically acceptable salt thereof for use in a method of cosmetic weight reduction wherein the strontium is administered at a dose of 20 mg to 70 mg per day in an oral care composition e.g. a toothpaste or a mouthwash.

8. Strontium, or a pharmaceutically acceptable salt thereof for use in a method according to claim 7, wherein said oral care composition is a toothpaste formulation comprising the following ingredients:76-92 % (w / w) demineralized water, 3-6 % (w / w) xylitol, 2-10 % (w / w) strontium chloride, 0.1-1 % (w / w) stevia, 0.01-0.5 % (w / w) sodium benzoate, 0.01-0.5 % (w / w)menthae piperitae, 0.01-0.5 % (w / w) spearmint oil and 3-6 % (w / w) metolose or methylcellulose, wherein the sum of the ingredients is 100 % (w / w).

9. Strontium, or a pharmaceutically acceptable salt thereof for use according to claim 7, wherein said oral care composition is a mouthwash formulation comprising the following ingredients:Aqua, xylitol, strontium chloride, stevia, sodium benzoate, mentha piperita oil, mentha spicata flower extract.

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