Bio-Three Active Probiotic Complex Tablets 630 Tablets (BIO-THREE Toa)

Active probiotic tablets are commonly used to improve various symptoms caused by abnormal gut microbiota.

I. Basic Drug Information

1. Generic Name : Butyric Acid Bacteria Compound (Live Probiotic Preparation)
2. English Name : BIO-THREE®, BIO-THREE® Tablets, BIO-THREE® OD Tablets
3. Product Name : BIOSRI Co-disintegrating Powder, BIOSRI Co-disintegrating Tablet, BIOSRI Co-disintegrating Oral Disintegrating Tablet (Chinese equivalent: BIOSRI Co-disintegrating Powder, BIOSRI Co-disintegrating Tablet, BIOSRI Co-disintegrating Orally Disintegrating Tablet)
4. Dosage form :
   • Viosley Powder: Powder
   • Viossly compound tablets: Plain tablets (regular tablets)
   • ビオスリー OD Tablets: plain tablets (orally disintegrating tablets, i.e. orally disintegrating tablets)
5. Indications : To improve various symptoms caused by abnormal gut microbiota.
6. Element :

   Drug Name	Active ingredients	additive
   ビオスリーmatching powder	1g contains 50mg of lactic acid bacteria (Enterococcus faecium T-110), 50mg of butyric acid bacteria (Clostridium butyricum TO-A), and 50mg of saccharifying bacteria (Bacillus subtilis TO-A), formulated according to the required live bacteria count.	Polyvinyl alcohol, povidone, corn starch, lactose syrup and other substances
   ビオスリー combination tablets	One tablet contains 2mg of lactic acid bacteria, 10mg of butyric acid bacteria, and 10mg of saccharifying bacteria.	Corn starch, crystalline cellulose, low-substituted hydroxypropyl cellulose, lactose hydrate, hydroxypropyl cellulose, light anhydrous silica, talc, magnesium stearate
   ビオスリーmatching OD tablets	One tablet contains 2mg of lactic acid bacteria, 10mg of butyric acid bacteria, and 10mg of saccharifying bacteria.	Talc, sodium fumarate stearate, anhydrous calcium hydrogen phosphate, corn starch, lactose hydrate, low-substituted hydroxypropyl cellulose, crospovidone, and light anhydrous silica.

   
   

   Note: The strain names were changed in 2019. The lactic acid bacteria were changed from Streptococcus faecalis to Enterococcus faecium, and the saccharifying bacteria were changed from Bacillus mesentericus to Bacillus subtilis. Only the names were changed; the strains themselves are the same as when they were approved.

7. Characteristics :

   Drug Name	tone	odor	smell	shape	diameter	thickness	weight	Identification code
   ビオスリーmatching powder	White to slightly yellowish-brown	Odorless or with a slightly distinctive odor	-	-	-	-	-	ToYK202 (subcontracted product)
   ビオスリー combination tablets	White to slightly yellowish-brown	Odorless or with a slightly distinctive odor	Slightly sweet	Plain slices	8mm	4.2mm	200mg/tablet	TK03
   ビオスリーmatching OD tablets	White to slightly yellowish-brown	Odorless or with a slightly distinctive odor	Slightly sweet	Orally disintegrating tablets	6.5mm	2.5mm	100mg/tablet	TK04

II. Usage and Dosage

1. Viossly Powder : The usual adult dosage is 1.5-3g per day, divided into 3 oral doses. The dosage may be adjusted according to age and symptoms.
2. Viossly tablets : Adults usually take 3-6 tablets daily, divided into 3 oral doses. The dosage may be adjusted according to age and symptoms.
3. Viossly combined with OD tablets : Adults usually take 3-6 tablets a day, divided into 3 oral doses. The dosage may be adjusted according to age and symptoms. Although this drug disintegrates in the mouth, it is not absorbed through the oral mucosa and must be swallowed with saliva or water.

III. Taboos

IV. Precautions

1. Special populations : The document does not mention special precautions for medication use for special populations (such as pregnant women, breastfeeding women, children, the elderly, and those with liver or kidney dysfunction).
2. Medication instructions :
   • When taking tablets packaged in PTP (including regular tablets and OD tablets), patients should be instructed to remove the medication from the PTP liner before taking it to avoid accidentally swallowing the PTP liner. Because the PTP liner is hard and has sharp edges, accidental swallowing may pierce the esophageal mucosa and even cause perforation leading to serious complications such as mediastinitis.
   • OD tablets can be placed on the tongue and taken after they disintegrate due to saliva; water is not required. Alternatively, they can be taken with water.
3. Drug storage : Store at room temperature

V. Adverse Reactions

1. Allergic reactions : No allergic reactions associated with this drug are mentioned.
2. Digestive system reactions : No digestive system reactions related to this drug are mentioned.

Note: In 355 clinical cases of using Biosly powder and Biosly tablets, no side effects clearly caused by this drug were reported.

VI. Drug Interactions

VII. Pharmacological effects

1. Modulation of biomembrane function : No mention is made of the role of this drug in modulating biomembrane function.
2. Improvement of metabolic disorders : No mention is made of the role of this drug in improving metabolic disorders.
3. Regulating blood lipids : No mention was made of the role of this drug in regulating blood lipids.
4. Protecting blood vessels : No mention is made of the protective effect of this drug on blood vessels.
5. Other key pharmacological effects :
   • Normalization of intestinal flora : Saccharified bacteria promote the proliferation of Bifidobacteria and inhibit the growth of intestinal pathogens in the presence of lactic acid bacteria and butyric acid bacteria, thus restoring the intestinal flora to normal. After administration to infants with bacterial diarrhea, Bifidobacteria increased, and the ratio of "total anaerobic bacteria/total aerobic bacteria", an indicator of improved intestinal flora, increased significantly.
   • Enhanced symbiotic proliferation : When butyric acid bacteria and lactic acid bacteria are cultured together, the number of butyric acid bacteria increases by about 10 times compared to culture alone; when saccharifying bacteria culture filtrate is added, the number of lactic acid bacteria increases by about 10 times compared to culture alone.
   • Symbiotic intestinal regulation : Three types of active bacteria proliferate symbiotically in the intestine, inhibiting the growth of harmful bacteria and exerting an intestinal regulation effect by regulating the intestinal flora.
   • Inhibition of pathogenic bacteria : In continuous flow culture, the antagonistic effect of mixed culture of butyric acid bacteria and lactic acid bacteria on pathogenic bacteria such as Escherichia coli, Vibrio enteritidis, Shigella dysenteriae, Clostridium tetani, and MRSA is significantly stronger than that of culture of either bacterium alone; and it does not inhibit Bifidobacteria or lactic acid bacteria, maintaining a symbiotic relationship; for diarrhea caused by Salmonella in children, the strains contained in the drug inhibit Salmonella through symbiotic effects; after administration, it can increase the number of Bifidobacteria in the intestines of patients with abnormal defecation caused by endocrine system and collagen diseases, reduce the number of Clostridium perfringens, and improve symptoms.
   • Promotes the growth of beneficial bacteria : The administration can promote the growth of Bifidobacteria, and the metabolites of Bacillus subtilis TO-A have the effect of promoting the division of Bifidobacteria.

VIII. Pharmacokinetics

1. Absorption : No information was provided regarding the absorption of this drug.
2. excretion :
   • Distribution test (tablets, OD tablets) : Five hours after oral administration of tablets and OD tablets to rats, the distribution of bacterial strains in each digestive tract was detected: Lactobacillus (Enterococcus faecium T-110) and Bacillus subtilis (Bacillus subtilis TO-A) were approximately 4.0 log CFU/g in the small intestine, approximately 5.0 log CFU/g in the cecum, and approximately 5.0 log CFU/g in the large intestine; Butyric acid bacteria (Clostridium butyricum TO-A) were approximately 4.0 log CFU/g in all locations.
   • Excretion test (tablets, OD tablets) : Rats were orally administered tablets and OD tablets for 7 consecutive days, and the number of bacteria in the feces was detected. The number of lactic acid bacteria and saccharified bacteria in the feces was comparable to that during the administration period 24 hours after drug withdrawal (day 8), most of them were below the detection limit 48 hours after drug withdrawal (day 9), and all were below the detection limit 72 hours after drug withdrawal (day 10). The number of butyric acid bacteria was mostly below the detection limit 24 hours after drug withdrawal (day 8), and all were below the detection limit 48 hours after drug withdrawal (day 9).
3. Stability (in vitro test) :
   • Butyric acid bacteria and saccharifying bacteria remained stable after treatment in artificial gastric and intestinal fluids for 150 minutes.
   • After treatment in simulated gastric fluid at pH 1.2 for 20 minutes, the bacterial count of lactic acid bacteria decreased to below 4.00 log CFU/mL; after treatment in simulated gastric fluid at pH 2.0 for 150 minutes, the bacterial count decreased to 4.15 log CFU/mL; and after treatment in simulated gastric fluid and simulated intestinal fluid at pH 3.0 and above for 150 minutes, the count remained stable.
   • In vitro experiments combining gastric model pH changes and gastric emptying time showed that the tablets and OD tablets behaved indistinguishably within the 90% confidence interval, indicating biological equivalence.

IX. Clinical Research

1. Biosly combination powder clinical study :
   • Total number of cases : 336 (including 285 children and 51 adults)
   • Clinical results in young children :

     Disease Name	Number of valid cases / Total number of cases	Effectiveness (%)
     constipation	1/1	100
     Acute and chronic enteritis	44/45	97.8
     alternating diarrhea and constipation syndrome	3/5	60.0

   • Adult clinical outcomes :

     Disease Name	Number of valid cases / Total number of cases	Effectiveness (%)
     constipation	8/15	53.3
     Irritable bowel syndrome	2/4	50.0

2. Biosly combination tablets clinical study :
   • Total cases : 19 (adults)
   • The number of effective cases and efficacy rates for specific diseases were not listed in detail; only general clinical research was mentioned.
3. Biological equivalence studies :
   • Fecal bacterial count comparison test : SPF rats (10 rats per group) were given OD tablets (experimental preparation) and ordinary tablets (standard preparation) respectively, and the number of three strains of bacteria in feces was compared. The results showed that there was no difference in the change of fecal bacterial count between the two preparations, and they were biologically equivalent.
   • Comparative test of distribution in the digestive tract : SPF rats (10 rats per group) were given OD tablets and ordinary tablets respectively, and the distribution of the three strains in the digestive tract was compared. The results showed that there was no difference in the number of bacteria in each test site between the two preparations, and they were biologically equivalent.

10. Packaging Specifications

XI. Production Information

Manufacturer : Toa Pharmaceutical Industries Co., Ltd. (Toa Pharmaceutical Industry Co., Ltd.)