US-20260124134-A1 - INJECTABLE LYOPHILIZED FORMULATION INCLUDING BETA-NICOTINAMIDE MONONUCLEOTIDE AND INJECTABLE FORMULATION INCLUDING THE SAME AND METHODS OF PREPARING THEM

US20260124134A1US 20260124134 A1US20260124134 A1US 20260124134A1US-20260124134-A1

Abstract

The present invention relates to an injectable lyophilized formulation including beta-nicotinamide mononucleotide, an injectable formulation including the same, and methods of preparing them.

Inventors

SI HA KANG

Assignees

SI HA KANG

Dates

Publication Date: 20260507
Application Date: 20250922
Priority Date: 20241101

Claims (12)

1 . An injectable lyophilized formulation comprising beta-nicotinamide mononucleotide.
2 . The injectable lyophilized formulation of claim 1 , further comprising: one or more stabilizers selected from the group consisting of monosaccharides; disaccharides; and sugar alcohols.
3 . The injectable lyophilized formulation of claim 2 , wherein the stabilizer is i) one or more selected from the group consisting of mannitol, sorbitol, lactose, xylitol, trehalose, sucrose, maltose, and glucose, or ii) a combination of mannitol as a first stabilizer and one selected from the group consisting of xylitol, trehalose, sucrose, maltose, and glucose as a second stabilizer.
4 . The injectable lyophilized formulation of claim 1 , which has a pH of 3 to 8.
5 . The injectable lyophilized formulation of claim 1 , wherein the water content of the injectable lyophilized formulation is 5 (w/w) % or less.
6 . An injectable formulation in which the injectable lyophilized formulation of claim 1 is reconstituted in an infusion solution.
7 . The injectable formulation of claim 6 , which is for any one selected from the group consisting of intravenous, subcutaneous, intramuscular, intradermal, and intra-arterial administrations.
8 . The injectable formulation of claim 6 , wherein the dose of the beta-nicotinamide mononucleotide is administered in an amount of 1/20 to ½ of the amount determined to be therapeutically effective in oral administration.
9 . The injectable formulation of claim 6 , wherein the beta-nicotinamide mononucleotide is administered daily at a dose of 0.5 mg/kg to 500 mg/kg.
10 . The injectable formulation of claim 6 , wherein blood samples are collected at 5, 30, 60, 120, and 360 minutes after the administration of the injectable formulation to analyze using a NAD+/NADH assay kit, revealing that i) the mean blood NAD+ concentrations show an increase to 200% to 400% at each time point compared to placebo administration, and ii) the mean blood NADH concentrations show an increase to 150% to 300% at each time point, compared to placebo administration.
11 . A method of preparing an injectable lyophilized formulation, comprising: (a) preparing a solution containing beta-nicotinamide mononucleotide; and (b) lyophilizing the solution.
12 . A method of preparing an injectable formulation, comprising: (a) preparing a solution containing beta-nicotinamide mononucleotide; (b) preparing an injectable lyophilized formulation by lyophilizing the solution; and (c) reconstituting the injectable lyophilized formulation by adding an infusion solution.

Description

CROSS-REFERENCE TO RELATED APPLICATION This application claims priority to and the benefit of Korean Patent Application No. 10-2024-0153418, filed on Nov. 1, 2024 and Korean Patent Application No. 10-2025-0012349, filed on Jan. 31, 2025, the disclosure of which is incorporated herein by reference in its entirety. BACKGROUND 1. Field of the Invention The present invention relates to an injectable lyophilized formulation including beta (β)-nicotinamide mononucleotide, an injectable formulation including the same, and methods of preparing them. 2. Discussion of Related Art Globally, the increase in average life expectancy and improvements in living standards have intensified the demand for anti-aging or age-reversal. However, aging is the stage that follows maturity and is an inevitable process of all living organisms, occurring irreversibly over time and leading to death. Aging is influenced by genetic factors, lifestyle factors, and environmental factors. Although lifestyle and environmental improvements have occurred over the past centuries, the lack of a meaningful increase in maximum average life expectancy suggests that genetic factors paly the most critical role in aging. Taking this into consideration, improvement in genetic factors is expected to delay an aging rate and achieve the natural maximum lifespan. Among the genetic factors of aging, the accumulation of DNA damage is recognized, and maintenance of DNA stability is an important approach to suppressing aging and extending lifespan. Nicotinamide mononucleotide (NMN) was identified as a potential rejuvenation drug in 2016 after the research team of Prof. Shinichiro Imai (Washington, United States) confirmed a 16% lifespan extension in mice orally administered NMN. NMN, existing in the body, activates sirtuins, longevity-related genes, and is reduced with aging. NMN is a nucleotide that is naturally generated through a reaction between a nucleoside containing ribose and nicotinamide (NAM) and a phosphate group. It has two isomeric forms, α-NMN and β-NMN, with the β isomer being the active form. Such β-NMN has been marketed in the United States as an oral health supplement and nutraceutical. Since the oral formulation must pass through various digestive organs, only a part of the ingredient is absorbed, resulting in the need for a higher dosage. While sublingual administration exhibits the maximum 30% bioavailability, there is a problem of considerable interindividual variability depending on the characteristics of oral administration and the residence time under the tongue. In addition, the dosage of β-NMN nutraceuticals currently used in the United States is set at up to 1250 mg per day; however, due to the high cost of β-NMN, there is a limitation in consuming large amounts daily. Compared to such oral administration, the administration of an injectable formulation is an optimal method to deliver an exact dose rapidly and in a well-controlled manner, thereby achieving systemic effects. In addition, such injectable formulations have the advantage of having the same effect with a smaller dose than oral administration. However, in this case, the stability and safety of injectable formulations should be given important consideration. Therefore, in development of injectable formulations containing β-NMN, studies are needed to improve stability and safety. SUMMARY OF THE INVENTION The present invention is directed to providing an injectable lyophilized formulation including β-NMN. However, technical problems to be solved in the present invention are not limited to the above-described problems, and other problems which are not described herein will be fully understood by those of ordinary skill in the art from the following descriptions. According to one aspect of the present invention, there is provided an injectable lyophilized formulation including β-NMN. The injectable lyophilized formulation may further include one or more stabilizers selected from the group consisting of monosaccharides; disaccharides; and sugar alcohols. The stabilizer may be i) one or more selected from the group consisting of mannitol, sorbitol, lactose, xylitol, trehalose, sucrose, maltose, and glucose, or ii) a combination of mannitol as a first stabilizer and one selected from the group consisting of xylitol, trehalose, sucrose, maltose, and glucose as a second stabilizer. The injectable lyophilized formulation may have a pH of 3 to 8. The water content of the injectable lyophilized formulation may be 5 (w/w) % or less. In one embodiment of the present invention, an injectable formulation in which the lyophilized formulation is reconstituted in an infusion solution. The injectable formulation may be for any one selected from the group consisting of intravenous, subcutaneous, intramuscular, intradermal, and intra-arterial administrations. In the injectable formulation, the dose of the β-NMN may be administered in an amount of 1/20 to ½ of the amount determined to be therapeu