PepzinGI™ - Summary of Mechanism of Action
PepZinGI™, a novel crystalline chelated compound complex consisting of L-carnosine (N-β-alanyl-L-histidine) and zinc, was first synthesized by Hamari Chemicals, Ltd. in 1983 aiming at combining the two physiologically important substances in one entirely new molecule[1]. This special chelated form of the mineral zinc has a unique ability to exert its effects directly on the cells of the stomach lining. When zinc is complexed to L-carnosine, it dissociates in the stomach at a slower rate. This prolonged existence allows it to maintain its gastric healing effect over a longer period of time[2]. The dipeptide L-carnosine is found mainly in the muscles of vertebrate and zinc is an essential trace element which plays an important role in the body, for example at the active centers of over 300 enzymes [3].

Both L-carnosine and zinc have common pharmacological properties such as anti-oxidant, membrane stabilizing, immunomodulating, and tissue repairing effects, and their anti-ulcerogenic effects in animals have also been investigated independently [4][5].

After extensive pharmacological studies PepZinGI™ was found to have a unique anti-ulcer property with both cytoprotective and tissue repairing actions in acute and chronic ulcers. Various action mechanisms such as anti-oxidant[6], membrane stabilizing[7], prostaglandin-independent cytoprotective[8], wound healing[9] and anti-Helicobacter pylori[10] activities have been proposed for the anti-ulcer effect.

The most featured character of PepZinGI™ is that it adheres specifically to the ulcer legions and remains there for a long time[11], suggesting that this property plays a key role to heal ulcer. Various toxicological studies[12], on the other hand, proved that this compound has enough safety to undergo clinical evaluation.

Clinical studies for gastric ulcer patients. In the controlled double blind study, PepZinGI™, in an 8-week treatment showed significantly better effect than those of cetraxate hydrochloride, with little side effect[13].

Thus an NDA for PepZinGI™, both for the active ingredient and its formulation (15% granules), was filed at the end of 1991 in Japan.

In addition to the anti-ulcer effect, PepZinGI™ also has various potential of new clinical application to osteoporosis[14], taste and smell disorders[15], hepatitis[16], pancreatitis[17], muscular dystrophy[18], ulcerative colitis[19], wound[20], stomatitis[21], and so on, as evidenced by various pharmacological studies with this compound. Also much attention has been growing on PepZinGI™ as a dietary supplement or a health food to improve marginal zinc deficiency or even to prevent aging, because PepZinGI™ has a extraordinarily high oral bioavailability in terms of zinc[22] and the component L-carnosine recently appeared to have strong anti-glycation effect[23]. Glycation is a process in which proteins react with sugars under active oxygens to form inflexible crosslinked proteins, and has been implicated as strong contributors to many progressive diseases of aging.

PepZinGI™ Helps Relieve Occasional Discomfort
Clinical Trials
In a randomized, multi-center, placebo-controlled double blind study, 299 patients suffering with symptoms of gastric discomfort were randomly allocated to receive either a PepzinGI™ or a placebo, or a control drug or its placebo for 8 weeks. Improvement ratings for a range of symptoms were taken at various points during the trial and compared with before treatment data. Of the 258 people who completed the trial, 136 were in the PepzinGI™ group. Of the group, 92% of the participants were rated as “moderately improved” or better on an improvement scale across the category of symptoms including heartburn, tenderness, epigastric pain, diarrhea and constipation after 8 weeks. [13]

In another study, 28 patients with gastric discomfort were given a PepZinGI™ and monitored for 8 weeks. Improvement was rated on a scale of subjective and objective symptoms. After 4 weeks, the rate of those cases that were considered to be “significantly improved” was 68.4%. After eight weeks, the “significantly improved” number was 68.8%. Over 60% of these patients remained in the “significantly improved” category well after discontinuation of the treatment, suggesting a lasting effect of the PepZinGI™ beyond the time it is taken.[24]

Maintains a Healthy GI Environment
The mineral zinc in PepZinGI™ is a critical component to a number of physiological processes in our bodies. Some of these functions include growth and metabolism of cells, healing of wounds, and maintenance of carbohydrate and lipid metabolism.[2]

PepZinGI™ may also be able to favorably maintain the bacterial balance of the stomach and GI tract. Studies suggest that the PepZinGI™ may have effects on certain strains of harmful bacteria and, therefore, may be able to help maintain a GI environment that is favorable to health.[25] By supporting the bacterial balance in the stomach, PepZinGI™ can help maintain a healthy mucosal lining.

Supports the Health of Gastric Cells
PepZinGI™ has been studied for its ability to prevent free radical damage to gastric cells. The authors concluded that the zinc compound directly protected gastric mucosal cells from oxidant stress and alcohol induced damage.[26]

Additional research further confirms the gastro-protective effects of PepZinGI™. The authors concluded that the zinc compound exerted a beneficial protective effect against monochloramine-induced stomach lesions.[27]

The PepZinGI™ has also been shown to slow the development of aspirin induced stomach damage in rats. These results may suggest a role for PepZinGI™ in protecting gastric cells by occasionally reducing the levels of certain cytokines in minor inflammation of the stomach.[28]

[1] Matsukura, T; Takahashi, T; Nishimura, Y; Ohtani, T; Sawada, M; Shibata, K: Chem. Pharm. Bull. (1990), 38(11), 3140-6.
[2] Matsukura, T.; Tanaka, H: Biochemistry (Moscow) (2000), 65(7), 817-823.
[3] Walsh, CT; Sandstead, HH; Prasad, AS; Newberne, PM; Fraker, PJ: Environ. Health Perspect (1994), 102 Suppl 2, 5-46.
[4] Yamakawa, A: Showa Igakkai Zasshi. (1975), 35(2), 113-126.
[5] Cho, CH: Drug Dev. Res. (1989), 17(3), 185-197.
[6] Yoshikawa, T; Naito, Y; Tanigawa, T; Yoneta, T; Kondo, M: Biochim. Biophys. Acta (1991), 1115(1), 15-22.
[7] Cho, CH; Luk, CT; Ogle, CW: Life Sci. (1991), 49(23), PL189-PL194.
[8] Arakawa, T; Satoh, H; Nakamura, A; Nebiki, H; Fukuda, T; Sakuma, H; Nakamura, H; Ishikawa, M; Seiki, M; Kobayashi, K: Dig. Dis. Sci. (1990), 35(5), 559-66.
[9] Seiki, M; Aida, H; Ueki, S; Yoneta, T; Takemasa, T; Hori, Y; Morita, H; Chaki, K; Tagashira, E: Nippon Yakurigaku Zasshi (1992), 100(2), 165-72.
[10] Sunairi, M; Tanaka, N; Kuwayama, H; Nakajima, M: Yakuri to Chiryo (1994), 22(9), 3771-3775.
[11] Seiki, M; Aida, H; Mera, Y; Arai, K; Toyama, S; Furuta, S; Morita, H; Hori, Y; Yoneta, T; Tagashira, E: Nippon Yakurigaku Zasshi (1992), 99(4), 255-63.
[12] Matsuda, K; Mera, Y; Wada, H; Aruga, H; Saik, Y; Taniguchi, Y: Arzneim. Forsch. (1991), 41(10), 1036-1041.
[13] Miyoshi A, et al. Clinical evaluation of Z-103 on gastric ulcer - a multicenter double-blind comparative study with cetraxate hydrochloride. Jpn PharmTher 1992;20(1):199-223.
[14] Sugiyama T; Tanaka H; Kawai S: Journal of Bone and Mineral Metabolism (2000), 18(6), 335-338.
[15] Ikui, A; Ikeda M; Yoshikawa T; Kudo I; Onoda K; Kida A: Jibiinkou (1999), 92(7), 801-804.
[16] Takagi, H; Nagamine, T; Abe, T; Takayama, H; Sato, K; Otsuka, T; Kakizaki, S; Hashimoto, Y; Matsumoto, T; Kojima, A; Takezawa, J: Suzuki K; Sato S; Mori M. Journal of Viral Hepatitis (2001)        8(5) 367-71.
[17] Takeda, S; Yoshikawa, T; Morita, Y; Yoshida, N; Kondo, M: J. Clin. Biochem. Nutr. (1999), 26(3), 213-225.
[18] Tameyasu, T; Yamada, M; Tanaka, M; Takahashi, S: Japanese Journal of Physiology (2002), 52, 111-120.
[19] Yoshikawa, T; Yamaguchi, T; Yoshida, N; Yamamoto, H; Kitazumi, S; Takahashi, S; Naito, Y; Kondo, M: Digestion (1997), 58(5), 464-468.
[20] Watanabe, S; Wang, XE; Yoneta, T; Seto, K; Sato, N: Gastroenterology (1997), 112, 327A.
[21] Katayama, S; Nishizawa, K; Hirano, M; Yamamura, S; Momose, Y: J. Pharm. Pharm. Sci. (2000), 3(1), 114-117.
[22] Nishimura, Y; Yamagishi, Y; Ando, K; Saito, T; Matsukura, T: Biomed. Res. Trace Elem. (2001), 12(2), 159-167.
[23] Boldyrev, AA; Gallant, SC; Suhkich, GT: Biosci. Rep. (1999), 19 (6), 581-7.
[24] Misawa T, et al. Clinical study of Z-103 - clinical effects on gastric ulcer and influence on endocrine function. Jpn PharmTher 1992; 20(1):245-254.
[25] Kuwayama H, et al. Polaprezinc. Nippon Rinsho 2002 Feb; 60 Suppl 2:717-720.
[26] Hiraishi H, et al. Polaprezinc protects gastric mucosal cells from noxious agents through antioxidant properties in vitro. Aliment Pharmacl Ther 1999;13:261-269.
[27] Kato S, Nishiwaki H, et al. Mucosal ulcerogenic action of monochloramine in rat stomachs: effects of polaprezinc and sucralfate. Dig Dis Sci 1997;42(10):2156-2163.
[28] Naito Y, et al. Effects of polaprezinc on lipid peroxidation, neutrophil accumulation, and TNF-alpha expression in rats with aspirin-induced gastric mucosal injury.
       Dig Dis Sci 2001;46(4):845-851.

*The above information is from publicly available literatures and have not been evaluated by the Food and Drug Administration.
 This product is not intended to diagnose, treat, cure or prevent any disease.

  PepZinGI™ is a trademark of Hamari Chemicals, Ltd.