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Review Article

Recent Progress in Selective COX-2 Inhibitor Formulations and Therapeutic Applications - A Patent Review (2012-2022)

Author(s): Roopal Mittal*, Shailesh Sharma, Anu Mittal and Amit Mittal*

Volume 23, Issue 22, 2023

Published on: 10 May, 2023

Page: [2130 - 2141] Pages: 12

DOI: 10.2174/1389557523666230417102123

Price: $65

Abstract

Introduction: Cyclooxygenase (COX), in literature, known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme that is responsible for the formation of prostanoids, including thromboxane and prostaglandins from arachidonic acid. COX-1 does housekeeping activity, whereas COX- 2 induces inflammation. Continuous rise in COX-2 gives birth to chronic pain-associated disorders, i.e., arthritis, cardiovascular complications, macular degeneration, cancer, and neurodegenerative disorders. Despite their potent anti-inflammatory effects, the detrimental effects of COX-2 inhibitors coexist in healthy tissues. Non-preferential NSAIDs cause gastrointestinal discomfort, whereas selective COX-2 inhibitors exert higher cardiovascular risk and renal impairment on chronic use.

Methods: This review paper covers key patents published between 2012-2022 on NSAIDs and coxibs, highlighting their importance, mechanism of action, and patents related to formulation and drug combination. So far, several drug combinations with NSAIDS have been used in clinical trials to treat chronic pain besides combating the side effects.

Conclusion: Emphasis has been given on the formulation, drug combination, administration routesmodification, and alternative routes, i.e., parenteral, topical, and ocular DEPOT, improving its riskbenefit ratio of NSAIDs to improvise their therapeutic availability and minimize the adverse effects. Considering the wide area of research on COX-2 and ongoing studies, and future scope of view for the better use of the NSAIDs in treating debilitating disease-associated algesia.

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Graphical Abstract

[1]
Ballerini, P.; Contursi, A.; Bruno, A.; Mucci, M.; Tacconelli, S.; Patrignani, P. Inflammation and Cancer: From the development of personalized indicators to novel therapeutic strategies. Front. Pharmacol., 2022, 13, 838079.
[http://dx.doi.org/10.3389/fphar.2022.838079] [PMID: 35308229]
[2]
Kolawole, O.R.; Kashfi, K. NSAIDs and cancer resolution: New paradigms beyond cyclooxygenase. Int. J. Mol. Sci., 2022, 23(3), 1432.
[http://dx.doi.org/10.3390/ijms23031432] [PMID: 35163356]
[3]
Kashfi, K. Anti-inflammatory agents as cancer therapeutics. Adv. Pharmacol., 2009, 57, 31-89.
[http://dx.doi.org/10.1016/S1054-3589(08)57002-5] [PMID: 20230759]
[4]
Balkwill, F.; Mantovani, A. Inflammation and cancer: Back to virchow? Lancet, 2001, 357(9255), 539-545.
[http://dx.doi.org/10.1016/S0140-6736(00)04046-0] [PMID: 11229684]
[5]
Freire, M.O.; Van Dyke, T.E. Natural resolution of inflammation. Periodontol. 2000, 2013, 63(1), 149-164.
[http://dx.doi.org/10.1111/prd.12034] [PMID: 23931059]
[6]
Kumar, R.; Clermont, G.; Vodovotz, Y.; Chow, C.C. The dynamics of acute inflammation. J. Theor. Biol., 2004, 230(2), 145-155.
[http://dx.doi.org/10.1016/j.jtbi.2004.04.044] [PMID: 15321710]
[7]
Medzhitov, R. Origin and physiological roles of inflammation. Nature, 2008, 454(7203), 428-435.
[http://dx.doi.org/10.1038/nature07201] [PMID: 18650913]
[8]
Mori, T.; Abe, I. Structural basis for endoperoxide-forming oxygenases. Beilstein J. Org. Chem., 2022, 18, 707-721.
[http://dx.doi.org/10.3762/bjoc.18.71] [PMID: 35821691]
[9]
Funk, C.D. Prostaglandins and leukotrienes: Advances in eicosanoid biology. Science, 2001, 294(5548), 1871-1875.
[http://dx.doi.org/10.1126/science.294.5548.1871] [PMID: 11729303]
[10]
Ahmadi, M.; Bekeschus, S.; Weltmann, K.D.; von Woedtke, T.; Wende, K. Non-steroidal anti-inflammatory drugs: Recent advances in the use of synthetic COX-2 inhibitors. RSC Medicinal Chemistry, 2022, 13(5), 471-496.
[http://dx.doi.org/10.1039/D1MD00280E] [PMID: 35685617]
[11]
Kaminska, B. MAPK signalling pathways as molecular targets for anti-inflammatory therapy-from molecular mechanisms to therapeutic benefits. Biochim. Biophys. Acta. Proteins Proteomics, 2005, 1754(1-2), 253-262.
[http://dx.doi.org/10.1016/j.bbapap.2005.08.017] [PMID: 16198162]
[12]
Lawrence, T. The nuclear factor B pathway in inflammation. Inflammation biology group. In: Cold Spring Perspect Biol; , 2009; 6, p. 9001651.
[http://dx.doi.org/10.1101/cshperspect.a001651]
[13]
Libby, P. Inflammatory mechanisms: The molecular basis of inflammation and disease. Nutr. Rev., 2007, 65(12)(Suppl. 3), 140-146.
[http://dx.doi.org/10.1301/nr.2007.dec.S140-S146] [PMID: 18240538]
[14]
Ferrero-Miliani, L.; Nielsen, O.H.; Andersen, P.S.; Girardin, S.E. Chronic inflammation: Importance of NOD2 and NALP3 in interleukin-1β generation. Clin. Exp. Immunol., 2007, 147(2), 227-235.
[http://dx.doi.org/10.1111/j.1365-2249.2006.03261.x] [PMID: 17223962]
[15]
Edinoff, A.; Sathivadivel, N.; McBride, T.; Parker, A.; Okeagu, C.; Kaye, A.D.; Kaye, A.M.; Kaye, J.S.; Kaye, R.J.M.; Sheth, M.; Viswanath, O.; Urits, I. Chronic pain treatment strategies in Parkinson’s Disease. Neurol. Int., 2020, 12(3), 61-76.
[http://dx.doi.org/10.3390/neurolint12030014] [PMID: 33218135]
[16]
Pálfy, M.; Reményi, A.; Korcsmáros, T. Endosomal crosstalk: Meeting points for signaling pathways. Trends Cell Biol., 2012, 22(9), 447-456.
[http://dx.doi.org/10.1016/j.tcb.2012.06.004] [PMID: 22796207]
[17]
Thannickal, V.J.; Fanburg, B.L. Reactive oxygen species in cell signaling. Am. J. Physiol. Lung Cell. Mol. Physiol., 2000, 279(6), L1005-L1028.
[http://dx.doi.org/10.1152/ajplung.2000.279.6.L1005] [PMID: 11076791]
[18]
Tichá, T. Lochman, J.; Činčalová, L.; Luhová, L.; Petřivalský, M. Redox regulation of plant S-nitrosoglutathione reductase activity through post-translational modifications of cysteine residues. Biochem. Biophys. Res. Commun., 2017, 494(1-2), 27-33.
[http://dx.doi.org/10.1016/j.bbrc.2017.10.090] [PMID: 29061305]
[19]
Chelombitko, M.A. Role of reactive oxygen species in inflammation: A minireview. Moscow Univ. Biol. Sci. Bull., 2018, 73(4), 199-202.
[http://dx.doi.org/10.3103/S009639251804003X]
[20]
Wang, L.; Cheng, C.K.; Yi, M.; Lui, K.O.; Huang, Y. Targeting endothelial dysfunction and inflammation. J. Mol. Cell. Cardiol., 2022, 168, 58-67.
[http://dx.doi.org/10.1016/j.yjmcc.2022.04.011] [PMID: 35460762]
[21]
Gupta, S.; Guleria, R.S. Involvement of nuclear factor-κB in inflammation and neuronal plasticity associated with post-traumatic stress disorder. Cells, 2022, 11(13), 2034.
[http://dx.doi.org/10.3390/cells11132034] [PMID: 35805118]
[22]
Ranneh, Y.; Ali, F.; Akim, A.M.; Hamid, H.A.; Khazaai, H.; Fadel, A. Crosstalk between reactive oxygen species and pro-inflammatory markers in developing various chronic diseases: A review. Appl. Biolo. Chem., 2017, 60(3), 327-338.
[http://dx.doi.org/10.1007/s13765-017-0285-9]
[23]
Henríquez-Olguín, C.; Altamirano, F.; Valladares, D.; López, J.R.; Allen, P.D.; Jaimovich, E. Altered ROS production, NF-κB activation and interleukin-6 gene expression induced by electrical stimulation in dystrophic mdx skeletal muscle cells. Biochim. Biophys. Acta Mol. Basis Dis., 2015, 1852(7), 1410-1419.
[http://dx.doi.org/10.1016/j.bbadis.2015.03.012] [PMID: 25857619]
[24]
Leto, T.L.; Geiszt, M. Role of Nox family NADPH oxidases in host defense. Antioxid. Redox Signal., 2006, 8(9-10), 1549-1561.
[http://dx.doi.org/10.1089/ars.2006.8.1549] [PMID: 16987010]
[25]
Balic, J.J.; Albargy, H.; Luu, K.; Kirby, F.J.; Jayasekara, W.S.N.; Mansell, F.; Garama, D.J.; De Nardo, D.; Baschuk, N.; Louis, C.; Humphries, F.; Fitzgerald, K.; Latz, E.; Gough, D.J.; Mansell, A. STAT3 serine phosphorylation is required for TLR4 metabolic reprogramming and IL-1β expression. Nat. Commun., 2020, 11(1), 3816.
[http://dx.doi.org/10.1038/s41467-020-17669-5] [PMID: 31911652]
[26]
Walker, J.G.; Ahern, M.J.; Coleman, M.; Weedon, H.; Papangelis, V.; Beroukas, D.; Roberts-Thomson, P.J.; Smith, M.D. Expression of Jak3, STAT1, STAT4, and STAT6 in inflammatory arthritis: unique Jak3 and STAT4 expression in dendritic cells in seropositive rheumatoid arthritis. Ann. Rheum. Dis., 2006, 65(2), 149-156.
[http://dx.doi.org/10.1136/ard.2005.037929] [PMID: 16096332]
[27]
Wegrzyn, J.; Potla, R.; Chwae, Y.J.; Sepuri, N.B.V.; Zhang, Q.; Koeck, T.; Derecka, M.; Szczepanek, K.; Szelag, M.; Gornicka, A.; Moh, A.; Moghaddas, S.; Chen, Q.; Bobbili, S.; Cichy, J.; Dulak, J.; Baker, D.P.; Wolfman, A.; Stuehr, D.; Hassan, M.O.; Fu, X.Y.; Avadhani, N.; Drake, J.I.; Fawcett, P.; Lesnefsky, E.J.; Larner, A.C. Function of mitochondrial Stat3 in cellular respiration. Science, 2009, 323(5915), 793-797.
[http://dx.doi.org/10.1126/science.1164551] [PMID: 19131594]
[28]
Gough, D.J.; Corlett, A.; Schlessinger, K.; Wegrzyn, J.; Larner, A.C.; Levy, D.E. Mitochondrial STAT3 supports Ras-dependent oncogenic transformation. Science, 2009, 324(5935), 1713-1716.
[http://dx.doi.org/10.1126/science.1171721] [PMID: 19556508]
[29]
Gough, D.J.; Marié, I.J.; Lobry, C.; Aifantis, I.; Levy, D.E. STAT3 supports experimental K-RasG12D–induced murine myeloproliferative neoplasms dependent on serine phosphorylation. Blood, 2014, 124(14), 2252-2261.
[http://dx.doi.org/10.1182/blood-2013-02-484196] [PMID: 25150294]
[30]
Hodorogea, A.; Calinescu, A.; Antohe, M.; Balaban, M.; Nedelcu, R.I.; Turcu, G.; Ion, D.A.; Badarau, I.A.; Popescu, C.M.; Popescu, R.; Popp, C.; Cioplea, M.; Nichita, L.; Hulea, I.; Brinzea, A. Epithelial-mesenchymal transition in skin cancers: A review. Anal. Cell. Pathol., 2019, 2019, 1-11.
[http://dx.doi.org/10.1155/2019/3851576] [PMID: 31934531]
[31]
Kalluri, R.; Weinberg, R.A. The basics of epithelial-mesenchymal transition. J. Clin. Invest., 2010, 120(5), 1786.
[http://dx.doi.org/10.1172/JCI39104C1] [PMID: 19487818]
[32]
Thiery, JP; Acloque, H; Huang, RY; Nieto, MA Epithelial-mesenchymal transitions in development and disease. Cell., 2009, 139(5), 871-90.
[http://dx.doi.org/10.1016/j.cell.2009.11.007]
[33]
Wu, Y.; Zhou, B.P. Snail. Cell Adhes. Migr., 2010, 4(2), 199-203.
[http://dx.doi.org/10.4161/cam.4.2.10943] [PMID: 20168078]
[34]
Nieszporek, A.; Skrzypek, K.; Adamek, G.; Majka, M. Molecular mechanisms of epithelial to mesenchymal transition in tumor metastasis. Acta Biochim. Pol., 2019, 66(4), 509-520.
[http://dx.doi.org/10.18388/abp.2019_2899] [PMID: 31883362]
[35]
Thiery, J.P.; Sleeman, J.P. Complex networks orchestrate epithelial–mesenchymal transitions. Nat. Rev. Mol. Cell Biol., 2006, 7(2), 131-142.
[http://dx.doi.org/10.1038/nrm1835] [PMID: 16493418]
[36]
Dellambra, E.; Cordisco, S.; Delle Monache, F.; Bondanza, S.; Teson, M.; Nicodemi, E.M.; Didona, B.; Condorelli, A.G.; Camerino, G.; Castiglia, D.; Guerra, L. RSPO1-mutated keratinocytes from palmoplantar keratoderma display impaired differentiation, alteration of cell–cell adhesion, EMT-like phenotype and invasiveness properties: Implications for squamous cell carcinoma susceptibility in patients with 46XX disorder of sexual development. Orphanet J. Rare Dis., 2022, 17(1), 275.
[http://dx.doi.org/10.1186/s13023-022-02434-2] [PMID: 35854363]
[37]
Serrano-Gomez, S.J.; Maziveyi, M.; Alahari, S.K. Regulation of epithelial-mesenchymal transition through epigenetic and post-translational modifications. Mol. Cancer, 2016, 15(1), 18.
[http://dx.doi.org/10.1186/s12943-016-0502-x] [PMID: 26905733]
[38]
Ashrafizadeh, M.; Ang, H.L.; Moghadam, E.R.; Mohammadi, S.; Zarrin, V.; Hushmandi, K.; Samarghandian, S.; Zarrabi, A.; Najafi, M.; Mohammadinejad, R.; Kumar, A.P. MicroRNAs and their influence on the ZEB family: Mechanistic aspects and therapeutic applications in cancer therapy. Biomolecules, 2020, 10(7), 1040.
[http://dx.doi.org/10.3390/biom10071040] [PMID: 32664703]
[39]
Ricciardi, M.; Zanotto, M.; Malpeli, G.; Bassi, G.; Perbellini, O.; Chilosi, M.; Bifari, F.; Krampera, M. Epithelial-to-mesenchymal transition (EMT) induced by inflammatory priming elicits mesenchymal stromal cell-like immune-modulatory properties in cancer cells. Br. J. Cancer, 2015, 112(6), 1067-1075.
[http://dx.doi.org/10.1038/bjc.2015.29] [PMID: 25668006]
[40]
Stemmler, M.P.; Eccles, R.L.; Brabletz, S.; Brabletz, T. Non-redundant functions of EMT transcription factors. Nat. Cell Biol., 2019, 21(1), 102-112.
[http://dx.doi.org/10.1038/s41556-018-0196-y] [PMID: 30602760]
[41]
Shukla, R; Handa, M; Kohli, K; Keshwani, P; Musyuni, P Transdermal pharmaceutical composition of COX-2 inhibitors. India patent IN201911023614A, 2021.
[42]
Ribeiro, H.; Rodrigues, I.; Napoleão, L.; Lira, L.; Marques, D.; Veríssimo, M.; Andrade, J.P.; Dourado, M. Non-steroidal anti-inflammatory drugs (NSAIDs), pain and aging: Adjusting prescription to patient features. Biomed. Pharmacother., 2022, 150, 112958.
[http://dx.doi.org/10.1016/j.biopha.2022.112958] [PMID: 35453005]
[43]
Tuncay, E; Turkkan, S; Pehlivan, AN; Turkyilmaz, A Topical compositions comprising tolperisone and selective COX-2 inhibitor combination patent. WIPO patent WO2020086038A3, 2020.
[44]
Baati, T.; Bourasset, F.; Gharbi, N.; Njim, L.; Abderrabba, M.; Kerkeni, A.; Szwarc, H.; Moussa, F. The prolongation of the lifespan of rats by repeated oral administration of [60]fullerene. Biomaterials, 2012, 33(19), 4936-4946.
[http://dx.doi.org/10.1016/j.biomaterials.2012.03.036] [PMID: 22498298]
[45]
Prylutska, S.V.; Burlaka, A.P.; Prylutskyy, Y.I.; Ritter, U.; Scharff, P. Pristine C(60) fullerenes inhibit the rate of tumor growth and metastasis. Exp. Oncol., 2011, 33(3), 162-164.
[PMID: 21956470]
[46]
Chistyakov, V.A.; Smirnova, Y.O.; Prazdnova, E.V.; Soldatov, A.V. Possible mechanisms of fullerene C₆₀ antioxidant action. BioMed Res. Int., 2013, 2013, 1-4.
[http://dx.doi.org/10.1155/2013/821498] [PMID: 24222918]
[47]
Max, C. Nutraceutical compositions comprising C60 and COX-2 inhibitor. US patent US2020188331A1 2020.
[48]
Feng, Z.; Chu, F.; Guo, Z.; Sun, P. Synthesis and anti-inflammatory activity of the major metabolites of imrecoxib. Bioorg. Med. Chem. Lett., 2009, 19(8), 2270-2272.
[http://dx.doi.org/10.1016/j.bmcl.2009.02.090] [PMID: 19286379]
[49]
Mayoral Rojals, V.; Charaja, M.; De Leon Casasola, O.; Montero, A.; Narvaez Tamayo, M.A.; Varrassi, G. New insights into the pharmacological management of postoperative pain: A narrative review. Cureus, 2022, 14(3), e23037.
[http://dx.doi.org/10.7759/cureus.23037] [PMID: 35419225]
[50]
Gao, W; Hu, Y; Shen, T. Compound preparation of COX-2 inhibitor and tramadol patent. China Patent CN113521292A, 2021.
[51]
Ji, G.; Niu, J.; Shi, Y.; Hou, L.; Lu, Y.; Xiong, L. The effectiveness of repetitive paravertebral injections with local anesthetics and steroids for the prevention of postherpetic neuralgia in patients with acute herpes zoster. Anesth. Analg., 2009, 109(5), 1651-1655.
[http://dx.doi.org/10.1213/ANE.0b013e3181b79075] [PMID: 19713253]
[52]
Maziasz, T. Methods and compositions for the treatment of herpes virus infections using cyclooxygenase-2 selective inhibitors or cyclooxygenase-2 inhibitors in combination with antiviral agents patent. WIPO Patent WO2004056349A2, 2004.
[53]
Pridgen, WL Antiviral compound And COX-2 inhibitor combination therapy for functional somatic syndromes, including combination Of Famciclovir And Celecoxib patent. Canada Patent CA2863812C, 2019.
[54]
Pridgen, WL Antiviral compound and COX-2 inhibitor combination therapy for fibromyalgia patent. Spain Patent ES2769924T3, 2020.
[55]
Konnai, S.; Murata, S.; Okagawa, T.; Maekawa, N.; Nishimori, A.; Goto, S.; Suzuki, Y.; Nakajima, C.; Sajiki, Y. Combination use of inhibitor targeting PD-1/PD-L1 and COX-2 inhibitor patent. European Patent EP3656400A4, 2021.
[56]
Wu, MJ; Wu, PS; Lin, YL; Wu, PS COX-2 inhibitor, medicinal composition including the same and application thereof patent. Taiwan Patent TW202005647A 2020.
[57]
Tugrul, T; Kararli, SN; Karim, A Reconstitutable parenteral composition containing a COX-2 inhibitor patent. Hong Kong Patent HK1244690A1, 2018.
[58]
Pisak, MN Combinations of selective COX-2 inhibitor NSAIDs And H2 receptor antagonists for fast treatment of pain and inflammation patent. WIPO Patent WO2019135725A1, 2019.
[59]
Vrbanac, J.J. COX-2 inhibitors for the treatment of ocular disease patent. United States Patent US2020237715A1, 2020.
[60]
Hijos-Mallada, G.; Sostres, C.; Gomollón, F. NSAIDs, gastrointestinal toxicity and inflammatory bowel disease. Gastroenterol. Hepatol., 2022, 45(3), 215-222.
[http://dx.doi.org/10.1016/j.gastrohep.2021.06.003] [PMID: 34157367]
[61]
Wang, H.; Zhou, Y.; Sun, Q.; Zhou, C.; Hu, S.; Lenahan, C.; Xu, W.; Deng, Y.; Li, G.; Tao, S. Update on nanoparticle-based drug delivery system for anti-inflammatory treatment. Front. Bioeng. Biotechnol., 2021, 9, 630352.
[http://dx.doi.org/10.3389/fbioe.2021.630352] [PMID: 33681167]
[62]
Li, S.; Jiang, M.; Wang, L.; Yu, S. Combined chemotherapy with cyclooxygenase-2 (COX-2) inhibitors in treating human cancers: Recent advancement. Biomed. Pharmacother., 2020, 129, 110389.
[http://dx.doi.org/10.1016/j.biopha.2020.110389] [PMID: 32540642]

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