Regulatory Dichotomy of Sucralfate, Its history and the new Bioadhesive polymerized Sucralfate barrier therapy for Oral health, Oncology support and Gastrointestinal disorders

  • Ricky Wayne McCullough Translational Medicine Clinic & Research Center of Storrs Connecticut


Sucralfate is a biologically inert non-systemically acting compound. It requires polymerization for conversion into its biological active form, polymerized Sucralfate. Should this conversion occur in the body, using processes of the body to effect conversion subsequent to administering a dose, then the administered Sucralfate is a drug, as it enlists bodily functions to enact a chemical change. This form of Sucralfate should be regulated as drug. On the other hand, Sucralfate is manufactured as a polymerized product, requiring no bodily functions to enable its therapeutic effect, then this form of Sucralfate act as a medical device and should be regulated as such. This dichotomy of Sucralfate was first recognized by the US FDA in 2005 that subsequently cleared several polymerized Sucralfate barrier therapies as medical devices.
This review covers the history of the regulatory dichotomy or duality of Sucralfate, the biological basis for Sucralfate clinical effects and the regulatory position of several barrier therapies.

Keywords: Sucralfate barrier therapy, Polymerized sucralfate, bioadhesive barrier, medical device, Polymerization, CE mark, GERD, US FDA 510k


Download data is not yet available.


1. Nagashima R. Development and characteristics of sucralfate. J Clin Gastroenterol. 1981; 3(Suppl2):103-10. PMID 6798099
2. Hunter J. On the digestion of the Stomach after death. Philosh Trans. 1772; 62:447
3. Pavy FW. On the Immunity enjoyed by the Stomach from being digested by its own secretion during life. Philosh Trans. 1863; 153:61
4. Schiff M. Autodigestion of the Stomach after death and during life. Beitr Physiol. 1898; 4:405
5. de Klug F. Pourquoi les ferments protéolytiques ne digèrent-ils pas l'estomac et l'intestin sur le vivant? Arch. internat. physiol. 1907; 5:297
6. Irvine JC, Hynd A. Synthetical Aminoglucosides derived from d-glucosamine (Series). J Chem Soc Trans. 1911; 99:250; J Chem Soc Trans 1912: 101:1128 and J. Chem Soc Trans 1913; 103:41-56
7. Levine PA, Lopez-Suarez J. Mucins and Mucoids. J Biol Chem. 1918; 36(1):105-26
8. Whitlow JE. The protective role of gastric mucus against the proteolytic action of gastric secretion. Master’s Thesis. Loyola University Medical School; 1920.
9. Bradley HC, Hodges M. The effect of mucin and mucinoids on peptic digestion. J Lab Clin Med. 1934; 20:165.
10. Miller CO, Dunbar J. Change in viscosity of mucin with pH. Proc Soc Exper Biol Med. 1933; 30:627.
11. Atkinson AJ. Gastric mucin in the treatment of peptic ulcer. JAMA. 1932; 98(14):1153-156.
12. Babkin BP, Komarov SA. The influence of gastric mucus on peptic digestion. Can Med Assoc J. 1932; 27:463-69.
13. Hollander F, Stein J Laubeer FU. The consistency, opacity and columnar cell content of gastric mucus secreted under the influence of several mild irritants. Gastroenterol. 1946; 6:576.
14. Hollander F, Sonnenblick BP, Sober HA. Experimental impairment of the gastric mucous barrier in dogs. J Natl Cancer Inst. 1947; 7:361.
15. Hollander F. Secretion of gastric mucus in health and disease, in Postgraduate Gastroenterology. Bockus HL editor. Philidelphia, WB Saunders Company; 1950 .p. 39-52.
16. Janowitz HD, Hollander F. Some properties of cell-free gastric mucus. Fed Proc. 1951; 10:70.
17. Levey S, Sheinfeld S. The inhibition of the proteolytic action of pepsin by sulfate containing polysaccharides. Gastroenterology. 1954; 27:625-28.
18. Anderson W, Watt J. Inhibition of peptic activity, protection against histamine ulceration in the guinea pig and combination with gastric mucin by an algal polyanion. J Pharm Pharmacal. 1959; 11:318.
19. Bianchi RG, Cook DL. Anti peptic and anti ulcerogenic properties of a synthetic sulfated polysaccharide (SN-263). Gastroenterology. 1964; 47:409-14.
20. Cook DL, Eich S, Cammarata PS. Comparative pharmacology and chemistry of synthetic sulfated polysaccharides. Arch. int. Pharmacodyn. 1963; 144: 1-19
21. Cayer D, Raffin JM. Effect of Depepsin (amylopectin sulfate) in the treatment of peptic ulcer. Ann NY Acad Sci. 1967; 140:744-46.
22. Ishimori A. History of the Development of Sucralfate. In Sucralfate: From Basic Science to the Bedside, edited by Daniel Hollander, GNJ Tytgat. Chapter 4. New York: Plenum Press; 1995 .p. 35-44.
23. Nitta Y, Masaya K, Kawa-saki-shi N et al. Dissacharide polysulfate aluminium compound and method. US Patent 3,432,489; 1969 Mar 11.
24. Ishimori A. Mechanism of the Antipeptic Action of Anionic Carbohydrate and Its Clinical Application for the Treatment of Peptic Ulcer. Tohoku J Exp Med. 1971; 103:141-57.
25. Yamagata S, Ishimori A, Sato H et al. Clinical Evaluation of Pharmacotherapy for Peptic Ulcer with Antipepsin Agents by Double Blind Technique - Multicenter Clinical Study. Tohoku J Exp Med. 1973; 110:377-404.
26. US Food and Drug Administration. Carafate (Sucralfate) [Internet]. US FDA 1982 [cited 2019 Aug 03]. Available from: cfm?event=overview.process&Appl No=018333
27. US Food and Drug Administration. Carafate (Sucralfate)Suspension [Internet]. US FDA 1982 [cited 2019 Aug 03]. Available from: 2017/019183s019lbl.pdf
28. Sucralfate [Internet].; 2019 [cited 2019 Aug 04]. Available from:
29. Ishimori A. Safety experience with sucralfate in Japan. J Clin Gastroenterol. 1981; 3(Suppl2):169-173. PMID 6459363.
30. Oshea S. Office of Combination Products. Request for Designation Sucralfate HCl Topical Paste [Internet]. [cited 2019 Feb 12]. Available from: Information/RFDJurisdictional Decisions/ UCM113797.pdf
31. Nakazawa S, Nagashima R Samloff IM. Selective binding of sucralfate to gastric ulcer in man. Dig Dis Sci N S. 1981; 26;297-300.
32. Saski H, Hinohara Y, Tsunoda Y et al. Binding of sucralfate to duodenal ulcer in man. Scand J Gastroenterol. 1983; 18(suppl 83):13-14.
33. Pelaseyed T, Bergstrom JH, Gustafsson JK et al. The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system. Immunol Rev. 2014; 260:8-20.
34. Hollander F. The two-component mucous barrier- its activity in protecting the gastroduodenal mucosa against peptic ulderaton. AMA Arch Intern Med. 1954; 93(1): 107-20. doi: 10.1001/archinte.1954.00240250117009
35. France MM, Turner JR. The mucosal barrier at a glance. J Cell Sci 2017; 130:307-314; doi: 10.1242/jcs.193482
36. Atuma C, Strugala V, Allen A, Holm L. The adherent gastrointestinal mucus gel layer: thickness and physical state in vivo. Am J Physiol Gastrointest Liver Physiol. 2001; 280:G922-G929.
37. Johnansson MEV, Larsson JHM, Hansson GC. The two mucus layers of colon are organized by the MUC2 muncin, whereas the outer layer is a legislator of host-microbial interactions. Proc Natl Acad Sci USA. 2011; 108 (Suppl1):4569-665.
38. Van Putten JP, Strijbis K. Transmembrane mucins: signaling receptors at the intersection of inflammation and cancer, J Innate Immun. 2017; 9:281-99.
doi: 10.1159/000453594
39. Hoffmann W. TFF2, a MUC6-binding lectin stabilizing the gastric mucus barrier and more (Review). Intl J Oncol. 2015; 47:806-16. doi: 10.3892/ijo.2015.3090
40. Yu H, He Y, Zhang X et al. The Rat IgGFccBP and Muc2 C-Terminal Domains and TFF3 in Two Intestinal Mucus Layers Bind Together by Covalent Interaction. PLoS ONE. 2011; 6(5):e20334(p1-7).
41. Aihara E, Engevik KA, Montrose MH. Trefoil factor peptides and gastrointestinal function. Annu Rev Physiol. 2017; 79:357-80. doi:10.1146/annurev-physio-021115-105447
42. Morris GP. Binding of sucralfate to mucosal surface. In Sucralfate: from basic science to the bedside. Edited by Daniel Hollander and GNJ Tygat. New York: Plenum Press; 1995.
43. Cohen MM, Bowdler R, Gervais P et al. Sucralfate protection of human gastric mucosa against acute ethanol injury. Gastroenterol [Internet]. 1989 [cited 2019 Aug 02]; 96:292-98. Available from:
44. Tasman-Jones C, Morrison G, Thomsen L, vanDerwee M. Sucralfate interactions with gastric mucus. Am J Med
[Internet]. 1989 Jun 09 [cited 2019 Aug 02]; 86(suppl6A):5-9. Available from:
45. Masuelli L, Tumino G, Turriniani M et al. Topical use of sucralfate in epithelial wound healing: clinical evidence of molecular mechanisms of action. Rec Pat Inflamm Allergy Drug Disc. 2010; 4:25-26. PMID:19832693
46. Bar-Shalom D, Niels B, Hamburger J. Method of treating conditions of teeth and supporting tissue. US Patent 5,709,873; 1998 Jan 20.
47. McCullough RW. Molecular basis for soft tissue management of gingivitis, periodontitis and peri-implant mucositis using an FDA cleared inflammation-targeting hydrogel - high potency polymerized cross-linked sucralfate - A case series illustrated profile of a drug device (Orafate) and the clinical rationale for use Dent Oral Craniofac Res. 2017; 3(5):6-11.
doi: 10.15761/DOCR.1000219
48. Lalla RV, Bowen J, Barasch A et al. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2014; 120(10):1453-61. doi: 10.1002/cncr.28592
49. McCullough RW. Practice insights on patient care-management overview for chemoradiation toxic mucositis-guidelines, guideline-supported therapies and high potency polymerized cross-linked sucralfate (ProThelial).J Oncol Pharm Pract. 2019 Mar; 25(2):409-22. doi: 10.1177/1078155218758864.;
50. McCullough RW. Single agent anti-mucositis protocol for oral and gastrointestinal mucositis and other implications on current concepts regarding chemoradiation induced mucositis and its management from a phase IV post-market surveillance of ProThelial-high potency polymerized cross-linked sucralfate (HPPCLS). Eur J Oncol Pharm. 2015; 9 (2015/2):1-11.
51. Savarino V, Pace F, Scarpignato. Randomised clinical trial: mucosal protection combined with acid suppression in the treatment of non-erosive reflux disease- efficacy of Esoxx, a hyaluronic acid-chondroitin sulphate based bioadhesive formulation. Aliment Pharmacol Ther. 2017; 45:631-642. doi:10.111/apt.13914
52. Palmieri B, Merighi A, Corbascio D et al. Fixed combination of hyaluronic acid and chondroitin-sulphate oral formulation in a randomized double blind, placebo controlled study for the treatment of symptoms in patients with non-erosive gastroesophageal reflux. Eur Rev Med Pharmacol Sci. 2013; 17: 3272-78.
53. McCullough RW. Mucosa-Centric Clinical Effects of High Potency Sucralfate: 28 Day 83% Resolution of Undifferentiated Dyspepsia, 28 Day 83% Reversal of Sign & Symptoms of Co-Morbid IBS and 1 Week 80% Healing of GERD. Gastroenterol. 2014; 146(5,Suppl 1): S-263.
54. McElvanna K, Wilson A, Irwin T. Sucralfate paste enema: a new method of topical treatment for haemorrhagic radiation proctitis. Colorectal Dis. 2014; 16(4):281-84. doi:10.1111/codi.12507;
55. Riley SA, Gupta I, Mani V. A comparison of sucralfate and prednisolone enemas in the treatment of active distal ulcerative colitis. Scand J Gastroenterol. 1989; 24:1014-18.
28 Views | 36 Downloads
How to Cite
McCullough, R. “Regulatory Dichotomy of Sucralfate, Its History and the New Bioadhesive Polymerized Sucralfate Barrier Therapy for Oral Health, Oncology Support and Gastrointestinal Disorders”. International Journal of Drug Regulatory Affairs, Vol. 7, no. 3, Sept. 2019, pp. 40-47, doi: