•Ostivone®
•How Ostivone works:
•Two Ways to Increase Bone Density
•Pharmacokinetic of Ostivone
•Safety and Efficacy Study
•Acute Toxicity Study
•Chronic Toxicity Study on Beagle dogs
•Chronic Toxicity Study on rats

Ostivone top
The only non-hormonal, effecacious agent to increase bone density. It belongs to bioflavonoids. Bioflavonoids are ubiquitous compounds in plant kingdom and rarely in animal kingdom. TSI^®’s Ostivone is a non animal source material.

Bioflavonoids: benzo-gamma-pyrone

Ostivone: 7-isopropoxy-3-phenyl-4H-1-benzopyran-4-0ne

Naturally found: In most photosynthesizing plant cells

Pharmacology of bioflavonoids:

• Regulator of numerous enzymes
• Stimulation of oxidative mitochondria phosphorylation
• Balance between estrogenic and antiestrogenic effects
• Antimicrobial
• Spasmolytic
• Strong antioxydative

How Ostivone works: top

1. Stimulation of osteoblastic growth
2. Inhibition of osteoclastic activity and differentiation
3. Active in potentiating the effects of estrogen on bone tissue

Two Ways to Increase Bone Density top

• Inhibition of bone resorption, stimulation of osteoblastic cells, inhibition of osteoclastic activity, and differentiation
• Activation of bone formation

Pharmacokinetic of Ostivone top

• Metabolized by cells, mainly in the liver, and excreted in urine
• No significant accumulation in the body
• Absorption greatly enhanced by food
• 200 mg taken with meal, around 90% of total dose of Ostivone rapidly absorbed through the small intestine with a peak after 90 minutes of administration
• Extensively metabolized
• Excretion half life is 9.8 hours for Ostivone

Safety and Efficacy Study top
Title: The safety and efficacy on Osteoporosis: Long term clinical trial Sugioka, Yoichi and his research group, Clinical Research, Vol.63: No.4, 1986

Dose: 200 mg, 3 times daily

Subjects: 75 diagnosed with osteoporosis

Efficacy:

Pain relief: 58% at 4 weeks
Osteoporosis: 57% at 36 weeks, 87% at 48 weeks

Toxicity: none reported at 48 weeks

Acute Toxicity Study top
Acute Toxicity Study of Ipriflavone: in Mice and Rat

Kiyoshi Imai, et al., Pharmacology and Therapy, Vol. 13, No. 10, 1985

Conclusion: A single subcutaneous administration of Ipriflavone at the levels of 5,000, 2,500 and 1,250 mg/kg body weight (Human equivalent dose: 350,000, 175,500, 87,500 mg for 70 kg body weight) did not cause any death in mice and rat.

Chronic Toxicity Study on Beagle dogs top
A one year oral toxicity study of Ipriflavone on Beagle dogs

Tomonobu Tokiwa, et al., Applied Pharmacology, Vol. 31, No. 1, 1986

Experiment: 6 male and 16 female dogs were divided into four groups. Ipriflavone were given orally in gelatin capsules at doses of 150, 500, 1,500 mg/kg/day once daily for 52 weeks.

Results: The test compound (Ipriflavone) affected neither the body weight nor the food and water consumption.

There were no changes attributable to the compound in hematology, blood chemistry, urinalysis, ophthalmology, body temperature, electrocardiogram, heart rate, blood pressure, necropsy, organ weight, or histopathology.

Chronic Toxicity Study on rats top
A one year oral toxicity study of Ipriflavone on rats

Tadahiko Otaka, et al., Applied Pharmacology, Vol. 31, No. 1, 1986

Experiment: Ipriflavone was administered at dosages of 300, 1,000, 3,000 mg/kg/day for one year.

Results: There were no treatment related changes in general appearance, mortalities, water consumption, urinalysis, ophthamofunduscopy, hematology, gross pathology or histopathology.