GASTROINTESTINAL DISEASE - Xediton Pharmaceuticals

TERRAGASTRO® - Good health starts in the gut

®

Clinically proven to quickly relieve symptoms of common gastrointestinal disorders

TERRAGASTRO® - Good health starts in the gut2

GASTROINTESTINAL DISEASEReferred to as gastrointestinal diseases, they are common disorders which affect theesophagus, stomach, small and large intestines, rectum and other organs including thepancreas, liver and gallbladder.

Alterations in the bowel flora and its activities are now believed to be contributingfactors to many chronic and degenerative diseases such as:▪ Irritable Bowel Disease (IBD)▪ Irritable Bowel Syndrome (IBS)▪ Rheumatoid Arthritis

These conditions have all been linked to alterations in the intestinal microflora1

IRRITABLE BOWEL SYNDROME (IBS)Irritable Bowel Syndrome (IBS) is a considered to be a functional disorder characterized by abdominal pain and/or discomfort associated with altered bowel habits or defecation. Symptoms are not explained by structural or biochemical abnormalities and diagnostic testing does not display any viable disease process.

There are three main subtypes of IBS: constipation-predominant (IBS-C), diarrhea-predominant (IBS-D) and alternating or mixed (IBS-A). Urgency, bloating and feelings of incomplete bowel movements are also common in IBS.

To determine whether a person is just having temporary digestive distress or if they do have IBS, doctors use a standard called the Rome III criteria to make a confident diagnosis of IBS:

ROME III CRITERIASymptoms must be present for at least six months and have been experienced on at least three days of at least three months. Specifically, symptoms must consist of recurrent abdominal pain or discomfort with two or more of the following:

• Pain is relieved by a bowel movement• Onset of pain is related to a change in frequency of stool• Onset of pain is related to a change in the appearance of stool

The main pharmacologic treatments for IBS include:

▪ Laxatives▪ Antidiarrheals▪ Spasmolytics

▪ Antidepressants▪ Complementary and alternative medicine

TERRAGASTRO® - Good health starts in the gut 3

IRRITABLE BOWEL DISEASE (IBD)Irritable Bowel Disease (IBD) is characterized by chronic inflammation of the intestines. Examples of IBD include Ulcerative colitis (UC), Crohn’s Disease and Pouchitis. Although it can occur at any age, it is most common in teenagers and young adults. Treatment for IBD aims to reduce the inflammation and thereby control gastrointestinal however, currently there is no medical cure for IBD.

Colectomy may eliminate UC but reduces quality of life and increases the risk of complications. Current treatment options involve the use of 5-aminosalicyclic acid (5-ASA), corticosteroids and immunomodulatory medication. Prolonged treatment of mild to moderate IBD symptoms is usually carried out using 5-ASA while corticosteroids and immunomodulatory medications are used to treat more severe symptoms.


®

TERRAGASTRO® is a patent-protected probiotic formula for oral health combining strains of Lactobacillus plantarum (CECT 7484 and CECT 7485) and Pediococcusacidilactici (CECT 7483). This probiotic has beneficial properties for promoting favourable gut flora and helps support intestinal/gastrointestinal health.

MECHANISM OF ACTION

Enterochromaffin (EC) Cells: Secrete the neurotransmitter serotonin, into

the intestinal wall.

Serotonin: Binds to receptors on nerves to modulate motility, secretion

and sensation.

SERT (serotonin reuptake transporter): Mediates the uptake of

serotonin into epithelial cells to inactivate it.

Probiotic bacteria: Produce SCFAs that stimulate serotonin release and thus

may improve gut motility and sensation.

The strains in TERRAGASTRO® ferment the fibers normally found in the diet to produce high amounts of short chain fatty acids (SCFAs), such as acetic, propionic and especially, butyric acid.

SCFAs, especially butyric acid, are readily absorbed by intestinal mucosa and stimulate sodium and water absorption in the colon. Fecal SCFA profile of patients with IBS-D is characterized by lower concentrations of total SCFAs. Serotonin release modulates both gut motility and sensation. SCFAs are known to stimulate serotonin (5-HT) release in the colon, and butyric acid has been shown to decrease visceral sensitivity of the intestine in human volunteers. Therefore, in situ production of SCFAs by strains in the TERRAGASTRO® formula can be useful in modulating gut motility and reducing visceral pain.


PROBIOTICS AND GASTROINTESTINAL HEALTHProbiotics aid in a wide range of gastro-intestinal processes and functions, mainly promoting the presence of good bacteria in the gut which plays a vital role in the development and maintenance of the mucosal immune system. They also compete with the less friendly microbes for both food and attachment sites on

the receptor cells.

Lactobacillus plantarum is a gram-positive aerotolerant bacteria that fiercely attacks pathogenic bad bacteria in the body. By eradicating these bacteria, it helps the body’s native bacteria grow stronger and become more resistant to future invasions of pathogens3.

Pediococcus acidilactici is associated with enhanced immune responses. It produces several different antimicrobial compounds that lessen the number of pathogenic bacteria and actively competes against Listeria.

The strains in TERRGASTRO® have demonstrated more than 40% survival when sequentially exposed to the different physiological conditions found in the

digestive tract, before reaching the small intestine.

THE STRAINS IN THE FORMULA WERE

SELECTED BECAUSE OF THE FOLLOWING

PROPERTIES:

✓ Displays significant inhibitory activity against several pathogenic bacterial strains✓ Displays minimal antagonistic activity against common commensal strains of the

human gastrointestinal flora✓ Displays a lack of inhibitory activity between strains, which allows for combined

use in a single formula✓ Improves clinical symptoms such as weight loss and diarrhea✓ Significantly reduces acute (IL-6) and chronic (IFNγ) cytokines✓ Highly resistant to the conditions of the gastrointestinal environment✓ Ability to adhere to the intestinal epithelium, which allows the strains to remain in

the intestinal tract and exert their probiotic effects✓ Produces large amounts of short chain fatty acids (SCFAs), which are readily

absorbed by the intestinal mucosa and stimulate sodium and water absorption in the colon. Each strain in the formula is a strong producer of a different SCFA (either acetic, propionic or butyric acid, which are the three major SCFAs found in the intestine)


CLINICAL TRIALLorenzo-Zúñiga V et al. (2014) compared two probiotic doses of TERRAGASTRO® (high and

low) with a placebo within a randomized, double-blind environment. Treatment plans of

TERRAGASTRO® included 200mg (high dose) and 20mg (low dose) vegetable gelatin

capsules. The results were divided into 3 clinical measurements (days 0, 21 and 42)

among the 84 patients. At each clinical visit, patients were evaluated for IBSQoL and

Visceral Sensitivity Index (VSI). A weekly diary of global symptom relief (SGA) was also

monitored throughout the study2.

0

5

10

15

20

Baseline 3 Weeks 6 WeeksMe

dia

n IB

SQO

L Im

pro

vem

en

t IBSQoL Score Improvement

High Dose Low Dose Placebo

Figure 1: Improvement in median IBSQOL Score of all probiotic (high and low dose) and placebo treated patients after 3-and 6-weeks of treatment

A statistically significant improvement in IBS-related quality of life (QoL) was observed in both daily high dose and low dose probiotic treated groups compared to the control (placebo).

The effect is significant regardless of intent-to-treat or per protocol analysis. The improvement is clinically relevant, as median scores in both probiotic treated groups were nearly double the median improvement observed in the placebo group.

Table 1: Improvement in IBSQOL Score of all probiotic and placebo treated patients

TERRAGASTRO® was found to improve gut related well-being. 55% of probiotic-treated subjects were good responders (improvement > 15 points) regardless of probiotic dose, while only 17% of placebo-treated subjects achieved such as response (p<0.01).

Improvement in IBSQoL Score <10 10-15 >15

All probiotic-treated subjects 23.40% 21.30% 55.30%

Placebo 54.20% 29.20% 16.70%

0

2

4

6

8

10

12

14

Day 21 Day 24

VSI

TERRAGASTRO® Placebo


The Visceral Sensitivity Index (VSI) test also confirmed a significant improvement in the TERRAGASTRO® treatment group (P < 0.01, T-Test, Figure 3). Symptoms of IBS decreased for individuals taking TERRAGASTRO® as demonstrated by a reduction in the Disease Activity Index Score. (Disease Activity Index = weight loss + diarrhea + blood in stool) (Figure 3).

Figure 2: Improvement in Visceral Sensitivity Index (VSI) of TERRAGASTRO vs placebo treated patients

Figure 3: Improvement in Disease Activity Index of TERRAGASTRO® vs placebo treated patients

0

1

2

3

4

Healthy Controls Individuals TakingTERRAGASTRO®

UntreatedIndividuals

Dis

eas

e A

ctiv

ity

Ind

ex


CLINICAL EFFICACYIn vitro experiments have demonstrated that the three strains in TERRAGASTRO® can survive bowel transit and have the following properties:

Resistance to lysozyme antibacterial activity from saliva

Resistance to a gastric acid environment

Capacity to proliferate in the presence of bile salts

In vivo experiments have demonstrated that TERRAGASTRO® also exerts the following effects:

•Statistically significant reduction of clinical symptoms (specifically weight loss, diarrhea and blood in stools)

At the macroscopic level

•Statistically significant reduction of pro-inflammatory cytokines

At the molecular level

A statistically significant correlation was observed between the decrease of clinical symptoms and the decrease of pro-inflammatory

cytokine levels


SUPPLEMENT INFORMATIONOne box of TERRAGASTRO® contains 30 capsules.

Recommended Use: Source of probiotics. Could promote favourable gut flora and help support intestinal/gastrointestinal health.

Medicinal Ingredients (per capsule): Lactobacillus plantarum…………………….2.7 billion CFUPediococcus acidilactici…….………………..1.3 billion CFU

Non-medicinal Ingredients: Maltodextrin, silicon dioxide, hydroxypropyl methylcellulose, titanium dioxide.

Directions:Adults and adolescents (12 and over): Take one capsule daily.

Caution:This product is intended for adults and adolescents (12 years and older). Pregnant and breastfeeding women are advised to consult with their healthcare practitioner prior to using this product.

Storage: Store at room temperature.

TERRAGASTRO® has been registered with Health Canada; the Health Canada NPN number is: 80052841

Safety & Drug Interactions: Keep out of reach of children. If you are on antibiotics, take at least 2-3 hours before or after your antibiotics. If you have fever, vomiting, bloody diarrhea or severe abdominal pain, consult a health care practitioner prior to use. If symptoms of digestive upset (e.g. diarrhea) occur, worsen, or persist beyond 3 days, discontinue use and consult a healthcare practitioner. If you have an immune-compromised condition (e.g. AIDS, lymphoma, patients undergoing long-term corticosteroid treatment), do not use this product. Food supplements should not be used as a substitute for a varied balanced diet and healthy lifestyle. Keep in a fresh dry place.


FAQs1. How should TERRAGASTRO® be taken?

Take one capsule daily. For best results, take one capsule daily for at least two weeks.

2. Who should take TERRAGASTRO®?Individuals who want to maintain a good gastrointestinal health status or suffer from the following conditions: constipation predominant IBS (IBS-C), diarrhea predominant IBS (IBS-D), alternating or mixed IBS (IBS-A), ulcerative colitis, pouchitis and/or Crohn’s disease.

3. Are there any known side effects of taking TERRAGASTRO®?No, TERRAGASTRO® exerts no side effects on the individual.

4. Has TERRAGASTRO® been clinically tested?Yes, there are a number of trials that evaluated the efficacy of TERRAGASTRO®.

5. What benefits can my patient expect from TERRAGASTRO®?The components in TERRAGASTRO® help to promote favourable gut flora and helps support intestinal/gastrointestinal health.

6. Where is TERRAGASTRO® available?TERRAGASTRO® is available in stores and online at www.xediton.com/product/terragastro/ or by calling 1-905-286-9111.

CONTACT USXEDITON PHARMACEUTICALS INC2000 Argentia RoadMississauga, ONL5N 1W1Email: [email protected]

REFERENCES1Myers, S. P. (2004). The causes of intestinal dysbiosis: a review. Altern Med Rev, 9(2), 180-197. 2Lorenzo-Zúñiga, V. et al. (2014). I. 31, a new combination of probiotics, improves irritable bowel syndrome-related quality of life. World J Gastroenterology, 20(26), 8709-16, 3http://probiotics.mercola.com/probiotics-health-benefits.html


TERRAGASTRO® - Good health starts in the gut

TGDB01

GASTROINTESTINAL DISEASE - Xediton Pharmaceuticals

Documents