Sublingual oral spray for type 2 diabetes

Abstract

The invention relates to a sublingual oral spray for use in the treatment of type 2 diabetes, which is a liquid product stored under pressure in a spray device and dispensed as an aerosol, and which has a composition comprising orforglipron, purified water, glycerine, propylene glycol, ethanol, sodium citrate, sodium benzoate, and mint extract flavouring; and wherein, specifically, the product has a composition, expressed as a percentage of the total weight of the mixture, comprising: 4 - 9% orforglipron; 80 - 87.5% purified water; 4 - 6% glycerine; 2 - 4% propylene glycol; 2 - 4% ethanol; 0.30 - 2% sodium citrate; 0.10 - 1% sodium benzoate; and 0.10 - 10% mint extract flavouring.

Description

[0001] DESCRIPTION

[0002] SUBLINGUAL ORAL SPRAY FOR TYPE 2 DIABETES

[0003] Object of the invention

[0004] The present invention relates to a new type of spray or liquid product that, stored under pressure, is projected outwards in the form of an aerosol, and is intended to be used in the treatment of type 2 diabetes where the blood glucose level of a patient is too high compared to normal values.

[0005] The invention falls within the scope of the pharmaceutical industry and, more specifically, refers to a product to be used in patients with type 2 diabetes.

[0006] Background of the invention

[0007] It is now known that glucagon-like peptide-1 (GLP-1) receptor agonists have revolutionized the treatment of type 2 diabetes by providing sustained glycemic control and facilitating weight loss. The standard approach to managing this disease relies on subcutaneous injections and oral tablets. For example, oral coated tablets are commonly used to reduce glucose production in the liver and improve the body's sensitivity to insulin, allowing the body to use insulin more effectively. However, existing injectable and oral treatments are known to have limitations in terms of adherence and convenience.

[0008] In contrast to these known treatments, the present invention introduces a new type of product, specifically a sublingual oral spray, whose main component is orforglipron. This spray is designed to take advantage of the high bioavailability and rapid absorption offered by the oral mucosa, eliminating the need for daily injections or tablets. Sublingual administration of medications has proven to be an effective strategy for improving bioavailability, minimizing first-pass hepatic metabolism, and facilitating rapid systemic absorption. Administering medications via routes other than oral or injectable has gained interest in recent decades due to its advantages in terms of bioavailability, tolerability, and treatment adherence.Among these, sublingual administration stands out for its ability to bypass first-pass hepatic metabolism and provide sustained or immediate release as needed. These strategies have been successfully implemented in areas such as pain management (fentanyl), angina (nitroglycerin), and opioid dependence (buprenorphine).

[0009] In this regard, it is known that orforglipron is a non-peptide agonist of the GLP-1 receptor and has demonstrated efficacy in the management of type 2 diabetes in its oral formulation in recent clinical studies (e.g., "Efficacy and Safety of Oral Orforglipron in Patients with Type 2 Diabetes: A Multicentre, Randomised, Dose-Response, Phase 2 Study," Lancet, 2024). However, as with other oral treatments, its use is associated with some gastrointestinal side effects and the need for daily dosing, which can affect tolerance and adherence in certain patients.

[0010] The applicant is unaware of any commercially available product containing orforglipron in the form of an oral spray for the treatment of type II diabetes. Specifically, the present invention seeks to provide effective doses of orforglipron, given that injectable and oral tablet formulations containing this compound are known, but no pharmaceutical product similar to or as advantageous as the one described and claimed below is known.

[0011] Explanation of the invention

[0012] The invention is a product to be used in the treatment of type 2 diabetes that, in its different embodiments, solves the problems and limitations present in the state of the art previously raised.

[0013] The product of the present invention is a liquid composition stored under pressure in a spray device and projected externally as an aerosol. Its composition comprises orforglipron, purified water, glycerin, propylene glycol, ethanol, sodium citrate, sodium benzoate, and mint extract flavoring. More specifically, the product has a composition, expressed as a percentage of the total weight of the mixture, comprising:

[0014] 4-9% Orforglipron

[0015] 64 - 87.5% purified water

[0016] 4-6% Glycerin

[0017] 2-4% Propylene Glycol

[0018] 2-4% Ethanol

[0019] 0.30 - 2% Sodium Citrate

[0020] 0.10-1% sodium benzoate; and

[0021] 0.10 - 10% mint extract flavoring

[0022] where the

[0023] Orforglipron is the active ingredient in the composition; it acts on GLP-1 receptors to stimulate glucose-dependent insulin secretion and reduce glucagon release; in addition to having other anti-obesity effects such as slowing gastric emptying and promoting satiety and weight loss.

[0024] purified water acts as the base vehicle;

[0025] Glycerin improves adhesion to the mucosa and absorption;

[0026] Propylene glycol acts as a stabilizer and solubility enhancer;

[0027] Ethanol improves mucosal permeability;

[0028] Sodium citrate allows maintaining an optimal pH (around 6.8);

[0029] Sodium benzoate is an antimicrobial preservative; and

[0030] The natural flavoring of mint extract enhances the patient's sensory experience.

[0031] This formulation takes advantage of rapid absorption through the sublingual mucosa to provide sustained glycemic control. This active ingredient has been studied with a once-daily dose of 20 mg administered in four consecutive sprays (each 0.1 mL of product containing 5 mg of orforglipron), and it has been shown that 20 mg of orforglipron is sufficient to maintain therapeutic levels for 24 hours, thanks to its slow and prolonged elimination, preventing peaks and dips in concentration. The onset of action is approximately 15 minutes after sublingual administration, and the duration of effect is 24 hours. Furthermore, the slow elimination helps avoid concentration fluctuations, reducing the risk of adverse effects.

[0032] Studies have also shown that commercially available oral capsules containing norforglipron, at a dose of 25 mg / day, undergo 50% first-pass hepatic metabolism, resulting in only half the dose reaching the bloodstream in its active form. In contrast, this product, in sublingual spray form at a dose of 20 mg / day, exhibits improved bioavailability of 70-80%, meaning a slightly lower dose than the oral form is sufficient to achieve higher therapeutic plasma levels. Therefore, sublingual bioavailability is estimated to be 30-70% higher than oral bioavailability. Given this higher sublingual bioavailability, as previously discussed, the dose required to achieve plasma concentrations similar to those of the oral form should be lower, and gastrointestinal side effects are also reduced.

[0033] Regarding the product's advantages for the patient, it offers improved comfort, replacing injections with a quick and non-invasive oral application; it has better adherence, as the once-daily dosage has a pleasant taste; it is better assimilated by the body than oral compounds; and it is rapidly absorbed, with an effect in about 15 minutes thanks to the high sublingual vascularization. Specifically, it is more convenient to use, as it is non-invasive and easy to administer once a day; it has better bioavailability because it avoids first-pass metabolism; it is highly stable, allowing it to be stored at room temperature, and it contains no sensitive components; and it does not have common adverse effects such as irritation.In contrast, it is known that subcutaneous injections are painful, invasive, and require skill in self-injection by the patient; the speed of action depends on the subcutaneous depth of administration; they require stable storage in refrigerated vials or pre-filled devices; and they can cause local reactions at the injection site, such as pain or redness. It is also known that oral tablets are inconvenient, as daily intake can cause digestive discomfort; they have a slow speed of action because they pass through the digestive system and undergo first-pass metabolism; tablets are sensitive to humidity and temperature; and they can cause gastrointestinal discomfort.Furthermore, with regard to the manufacture and distribution of the product that is the subject of the present invention, there is the advantage of being a product with high acceptance among patients seeking non-invasive alternatives; and as for the process of obtaining it, existing technologies in oral sprays are used.

[0034] As for the product, it is stored in a spray device, comprising a dark, light-resistant glass bottle with a capacity of at least 5 mL, for at least 10 doses;

[0035] an anatomical nozzle for precise sublingual administration of the product;

[0036] an atomizing dispenser, calibrated to dispense 0.1 mL per shot; and

[0037] It may include a label with clear instructions for use and storage warnings.

[0038] Regarding the application of the product:

[0039] The preparation involves gently shaking the bottle before use and removing the protective cap;

[0040] The application involves placing the nozzle under the tongue and administering 5 consecutive sprays; and

[0041] Storage is based on keeping the device at room temperature (15-25 °C), protected from light and heat.

[0042] It should be noted that, throughout the description and claims, the term includes and its variants are not intended to exclude other technical features or additional elements.

[0043] Brief description of the figures

[0044] In order to complete the description and to aid in a better understanding of the characteristics of the invention, a figure is presented which, for illustrative and non-limiting purposes, represents the following:

[0045] Figure 1: Shows a schematic view of the sublingual oral spray for use in the treatment of type 2 diabetes, the subject of the present invention, where it can be seen that the composition comprising Orforglipron, purified water, Glycerin, Propylene glycol, Ethanol, Sodium citrate, Sodium benzoate; and mint extract flavoring, is stored in a spray device, comprising a dark, light-resistant glass bottle (1); an anatomical nozzle (2) for precise administration of the product; an atomizing dispenser (3); and a label (4) including information and instructions for dispensing the product. Detailed explanation of an embodiment of the invention

[0046] A preferred embodiment of the invention consists of a liquid product that is stored under pressure in a spray device and is projected outward as an aerosol, comprising a 10 mL dark, light-resistant glass bottle (1) intended for 20 doses; an anatomical nozzle (2) for precise sublingual administration of the product; an atomizing dispenser (3) calibrated to dispense 0.1 mL per spray; and a label (4) including instructions for use of the product and storage warnings, wherein the composition of the product is such that a daily dose of 0.5 mL of the product comprises 20 mg of Orforglipron; 0.025 mL of glycerin (5% of the dose); 0.015 mL of propylene glycol (3% of the dose); 0.015 mL of ethanol (3% of the dose); 0.005 of Sodium Citrate (1% of the dose; 0.001 mL of Sodium Benzoate (0.2% of the dose); 0.025 mL of mint flavoring; and the rest of the product up to 100% of the dose of purified water as the base vehicle.

[0047] As previously mentioned, studies have shown that this composition, with an active ingredient at a dose of 20 mg / day, has a bioavailability of 70-80%, compared to a bioavailability of 50% in oral tablets. Sublingual bioavailability is 30-70% higher than oral bioavailability, meaning that the dose needed to achieve plasma concentrations similar to those of the oral form is lower, and gastrointestinal side effects that can occur when oral tablets are ingested are reduced.

Claims

CLAIMS 1.~ Sublingual oral spray for type 2 diabetes, characterized in that it is a liquid product that is stored under pressure in a spray device and is projected outwards in the form of an aerosol, and having a composition comprising Orforglipron, purified water, Glycerin, Propylene glycol, Ethanol, Sodium citrate, Sodium benzoate; and mint extract flavoring.

2. A spray according to claim 1, wherein the product has a composition, expressed as a percentage of the total weight of the mixture, comprising: 4-9% Orforglipron 64 - 87.50% purified water 4-6% Glycerin 2-4% Propylene Glycol 2-4% Ethanol 0.30 - 2% Sodium Citrate 0.10 - 1% Sodium Benzoate; and 0.10 - 10% mint extract flavoring 3.- A spray, according to claim 1, wherein the spraying device comprises a dark light-resistant glass bottle (1); an anatomical nozzle (2) for sublingual administration of the product and an atomizing dispenser (3). 4.- A spray, according to claim 3, wherein the bottle (1) has a capacity of at least 5 mL.

5. A spray, according to claim 3, wherein the atomizer dispenser (3) is calibrated to dispense 0.1 mL per spray 6. Use of a spray according to any of the preceding claims for the treatment of type 2 diabetes.

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