IP Library › Granted Patent US 12,226,385
Granted Patent B2
US 12,226,385 · App. 17/840,532 · Granted Feb 18, 2025

Synergistic composition for activating intracellular secondary messenger(cAMP) pathway

Inventors: Rajaram Samant (Thane, IN); Rajendra Prasad Tongra (Jaipur, IN); Jotiram Palkar (Thane, IN)
Assignee: CELAGENEX RESEARCH (INDIA) PRIVATE LTD.
A61K31/197A61K9/485A61K9/4858A61K9/4866A61K31/155A61P25/28
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Quick Facts
Patent No.
US 12,226,385
App. No.
17/840,532
Granted
Feb 18, 2025
Kind
B2
Abstract

The invention discloses herein related to synergistic combination of exogenous bioactives for activating intracellular secondary messenger (cAMP) signalling pathway. Particularly, the invention relates to synergistic compositions comprising combination of therapeutically effective amount of (3R)-3-acetyloxy-4-(trimethylazaniumyl) butanoate and N-4-aminobutylguanidine and salts thereof present in a weight ratio of 1:0.01 to 1:2 along with pharmaceutically acceptable excipients. Furthermore, the composition is useful for treating disease conditions or disorders related to depletion of secondary messenger pathway. The present invention further provides method of treating disease conditions related mental illness or disorder.

Claims (6)

1. A method of treating depression, the method comprising:

administering a unit dose of a bioactive composition twice daily to male and female subjects aged in a range of 18 to 65 years for a period of 12 weeks; and thereby

wherein the unit dose of the bioactive composition comprises:

a therapeutically active exogenous combination consisting of (3R)-3-acetyloxy-4-(trimethylazaniumyl) butanoate and N-(4-aminobutyl) guanidine or a salt thereof, wherein the (3R)-3-acetyloxy-4-(trimethylazaniumyl) butanoate is present in an amount of 500 mg and the N-(4-aminobutyl) guanidine or the salt thereof is present in an amount of 250 mg; and

pharmaceutically acceptable excipients.

2. The method as claimed in claim 1 , wherein the pharmaceutically acceptable excipients comprise a diluent, a binder, a lubricant, a glidant, an additive, a surfactant, a stabilizer, an antioxidant and a plasticizer; and wherein the diluent is present in a range of 1 to 30%; the binder is present in a range of 0.5 to 25%; the lubricant is present in a range of 0.1 to 10.0%; the glidant is present in a range of 0.1 to 5.0%; the additive is present in a range of 0.1 to 10%; the surfactant is present in a range of 0.1 to 5.0%; the stabilizer is present in a range of 0.1 to 5.0%; the antioxidant is present in a range of 0.1 to 5.0%; and the plasticizer is present in a range of 0.1 to 5.0%, each by weight of a total of the bioactive composition.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 26, 2022
From: TONGRA, RAJENDRA PRASAD
To: CELAGENEX RESEARCH (INDIA) PRIVATE LTD.
Reel/Frame 060923/0450 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 14, 2022
From: SAMANT, RAJARAM; PALKAR, JOTIRAM
To: CELAGENEX RESEARCH (INDIA) PRIVATE LTD.
Reel/Frame 060511/0794 →
Priority Claims (1)
IN 202121051996 · Nov 12, 2021 · national
Continuity (1)
Related Publication 20220313638A1 · Oct 6, 2022
References Cited (35)
US 5677349A · Gilad et al. · 1997 [cited by applicant]
US 10130602B2 · Williams et al. · 2018 [cited by applicant]
US 20040009926A1 · Pettegrew · 2004 [cited by examiner]
US 20090069331A1 · Vallance et al. · 2009 [cited by applicant]
US 20180054348A1 · Luo et al. · 2018 [cited by applicant]
US 20180303896A1 · Cross, III · 2018 [cited by examiner]
SG 11201900269A · 2019 [cited by applicant]
WO 2002096411A1 · 2002 [cited by applicant]
WO 2006051314A8 · 2006 [cited by applicant]
WO 2007120096A1 · 2007 [cited by applicant]
WO 2018226732A1 · 2018 [cited by applicant]
Gad M. Gilad, Varda H. Gilad, Evidence for oral agmatine sulfate safety—A 95-day high dosage pilot study with rats, Food and Chemical Toxicology, 2013, 62:758-762. (Year: 2013). [cited by examiner]
Remington, “Tablet Ingredients”, Remington: The Science and Practice of Pharmacy, 21st Edition, Beringer et al. Editors, 2005, pp. 891-894. (Year: 2005). [cited by examiner]
Kingchem, “N-Acetyl-L-Carnitine HCl”, Kingchem.com, 2018, 4 pages, downloaded from “www.Kingchem.com/nutritional/n-acetyl-l-carnitine-hcl/” on Aug. 24, 2022. (Year: 2018). [cited by examiner]
Chem Impex, “Agmatine sulfate”, ChemImpex.com, 2018, 2 pages, downloaded from “www. chemimpex.com/agmatine-sulfate” on Aug. 23, 2022. (Year: 2018). [cited by examiner]
Tanvi M. Deshpande, Anisul Quadir, Sakae Obara, Stephen W. Hoag. Impact of formulation excipients on the thermal, mechanical, and electrokinetic properties of hydroxypropyl methylcellulose acetate succinate (HPMCAS), In… [cited by examiner]
Kalasz, H., & Antal, I. (2006). Drug excipients. Current Medicinal Chemistry, 13(21), 2535-63. (Year: 2006). [cited by examiner]
Chou, T.C.,Cancer Res., 2010, 70(2), 440-446 (Year: 2010). [cited by examiner]
Berenbaum. Clin. Exp. Immunol., 1977, 28, 1-18 (Year: 1977). [cited by examiner]
Shopsin, B. (2013). The clinical antidepressant effect of exogenous agmatine is not reversed by parachlorophenylalanine: A pilot study. Acta Neuropsychiatrica, 25(2), 113-118. (Year: 2013). [cited by examiner]
Keynan O, Mirovsky Y, Dekel S, Gilad VH, Gilad GM. Safety and Efficacy of Dietary Agmatine Sulfate in Lumbar Disc-associated Radiculopathy. An Open-label, Dose-escalating Study Followed by a Randomized, Double-blind, Pl… [cited by examiner]
Maia Pujara et al., “Mechanisms of Reward Circuit Dysfunction in Psychiatric Illness: Prefrontal-Striatal Interactions,” The Neuroscientist, vol. 20, Issue 1, Aug. 7, 2013, pp. 82-95. [cited by applicant]
Salgado et al., “The Nucleus Accumbens: A Comprehensive Review,” Stereotact Funct Neurosurg, vol. 93, Feb. 18, 2015, pp. 75-93. [cited by applicant]
Mavridis, “The role of the nucleus accumbens in psychiatric disorders,” Psychiatriki, vol. 25, Issue No. 4, Oct.-Dec. 2015, pp. 282-294. English Abstract. [cited by applicant]
Lee et al., “The indirect efect of peer problems on adolescent depression through nucleus accumbens volume alteration,” Scientific Reports, vol. 10, Article No. 12870, Jul. 30, 2020, 9 pages. [cited by applicant]
Narayanaswamy, “Clinical correlates of nucleus accumbens volume in drug-naïve, adult patients with obsessive-compulsive disorder,” Australian & New Zealand Journal of Psychiatry 47(10), Jun. 4, 2013 pp. 930-937. [cited by applicant]
Zhang et al., “Reduced Neuronal cAMP in the Nucleus Accumbens Damages Blood-Brain Barrier Integrity and Promotes Stress Vulnerability,” vol. 87, Issue 6, Mar. 15, 2020, pp. 526-537. [cited by applicant]
Ferro, “Mechanistic target of rapamycin modulation: an emerging therapeutic approach in a wide variety of disease processes,” Br J Clin Pharmacol. 82(5), Oct. 12, 2016, pp. 1156-1157. [cited by applicant]
Masi et al., “Effects of Long-Term Acetyl-L-Carnitine Administration in Rats—II: Protection Against the Disrupting Effect of Stress on the Acquisition of Appetitive Behavior,” Neuropsychopharmacology, vol. 28, Oct. 1, 2… [cited by applicant]
Valverde et al., “Agmatine as a novel candidate for rapid-onset antidepressant response,” World J Psychiatry, vol. 11. Issue No. 11, Nov. 19, 2021, pp. 981-996. [cited by applicant]
Olescowicz et al., “Protective Effects of Agmatine Against Corticosterone-Induced Impairment on Hippocampal mTOR Signaling and Cell Death, ” Neurotoxicity Research, vol. 38, May 12, 2020, pp. 319-329. [cited by applicant]
Chen et al., “Evidence of Reduced Agmatine Concentrations in the Cerebral Cortex of Suicides,” International Journal of Neuropsychopharmacology, vol. 21, Issue 10, Jul. 9, 2018, pp. 895-900. [cited by applicant]
Shopsin, “The clinical antidepressant effect of exogenous agmatine is not reversed by parachlorophenylalanine: a pilot study,” Acta Neuropsychiatrica, Cambridge University Press, Feb. 26, 2013, abstract. [cited by applicant]
PCT International Search Report in Application No. PCT/IN2022/05044 Dated Sep. 16, 2022. [cited by applicant]
IN Office Action in Application No. 202121051996 Dated Jul. 14, 2022. [cited by applicant]