U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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Zoledronic acid (Reclast, Aclasta, Zometa) is an intravenous, highly potent amino-bisphosphonate approved worldwide, including in the USA, EU and Japan for use in patients with primary or secondary osteoporosis or low bone mass (approved indications vary between countries). Its high affinity to and long half-life in bone, and long duration of action allow for once-yearly administration, which has the potential to improve adherence to therapy. Zoledronic acid once yearly for up to 3 years improved bone mineral density (BMD) at several skeletal sites, reduced fracture risk and bone turnover, and/or preserved bone structure and mass relative to placebo in clinical studies in patients with primary or secondary osteoporosis. While additional benefits were seen when treatment was continued for up to 6 years, as evidenced by a reduced risk of vertebral fractures and higher BMD relative to 3 years’ therapy, there was the minimal advantage of treatment beyond 6 years. Therefore, in patients with low fracture risk, treatment discontinuation should be considered after approximately 5 years’ therapy. Zoledronic acid administered annually or once in 2 years was also effective in preventing bone loss in patients with low bone mass. Zoledronic acid was generally well tolerated, with the most common adverse events (AEs) being transient, mild-to-moderate post-infusion symptoms, which decreased with subsequent infusions.
Phosphoric acid, also known as orthophosphoric acid, is used in dentistry and orthodontics to clean and roughen the surfaces of teeth where dental appliances or fillings will be placed. In addition, this acid is a part of product ProcalAmine, which is indicated for peripheral administration in adults to preserve body protein and improve nitrogen balance in well-nourished, mildly catabolic patients who require short-term parenteral nutrition. In combination with dextrose (glucose) and levulose (fructose), phosphoric acid relieves nausea due to upset stomach from intestinal flu, stomach flu, and food or drink indiscretions. In addition, homeopathic product, Brain power contains also phosphoric acid and this product is used to temporarily relieve symptoms of general physical weakness and listlessness, including: fatigue; sore muscles & joints; dry skin; absence of sexual desire; occasional sleeplessness.
Status:
First marketed in 1921
Source:
Sodium Chloride U.S.P.
Source URL:

Class (Stereo):
CHEMICAL (ACHIRAL)



Hydroxocobalamin (also hydroxycobalamin, OHCbl) is a natural form, or vitamer, of vitamin B12. It is a member of the cobalamin family of compounds. Hydroxocobalamin, the active ingredient in Cyanokit, is cobinamide dihydroxide dihydrogen phosphate (ester), mono (inner salt), 3’-ester with 5,6-dimethyl-1-α-D-ribofuranosyl-1H-benzimidazole. The drug substance is the hydroxylated active form of vitamin B12 and is a large molecule in which a trivalent cobalt ion is coordinated in four positions by a tetrapyrol (or corrin) ring. It is a hygroscopic, odorless, dark red, crystalline powder that is freely soluble in water and ethanol, and practically insoluble in acetone and diethyl ether. Cyanokit contains hydroxocobalamin, an antidote indicated for the treatment of known or suspected cyanide poisoning. Cyanide is an extremely toxic poison. In the absence of rapid and adequate treatment, exposure to a high dose of cyanide can result in death within minutes due to the inhibition of cytochrome oxidase resulting in arrest of cellular respiration. Specifically, cyanide binds rapidly with cytochrome a3, a component of the cytochrome c oxidase complex in mitochondria. Inhibition of cytochrome a3 prevents the cell from using oxygen and forces anaerobic metabolism, resulting in lactate production, cellular hypoxia and metabolic acidosis. In massive acute cyanide poisoning, the mechanism of toxicity may involve other enzyme systems as well. Signs and symptoms of acute systemic cyanide poisoning may develop rapidly within minutes, depending on the route and extent of cyanide exposure. The action of Cyanokit is based on its ability to bind cyanide ions. Each hydroxocobalamin molecule can bind one cyanide ion by substituting it for the hydroxo ligand linked to the trivalent cobalt ion, to form cyanocobalamin, which is then excreted in the urine.
Status:
US Approved OTC
Source:
21 CFR 331.11(e) antacid:citrate-containing citrate (containing active ingredients: citrate ion, as citric acid or salt)
Source URL:
First marketed in 1921
Source:
Potassium Citrate U.S.P.
Source URL:

Class (Stereo):
CHEMICAL (ACHIRAL)



Potassium citrate is indicated for the management of renal tubular acidosis with calcium stones, hypocitraturic calcium oxalate nephrolithiasis of any etiology, uric acid lithiasis with or without calcium stones. WhenPotassium citrate is given orally, the metabolism of absorbed citrate produces an alkaline load. The induced alkaline load in turn increases urinary pH and raises urinary citrate by augmenting citrate clearance without measurably altering ultrafilterable serum citrate. Thus, potassium citrate therapy appears to increase urinary citrate principally by modifying the renal handling of citrate, rather than by increasing the filtered load of citrate. Potassium citrate is used as a food additive (E 332) to regulate acidity.
Status:
Investigational
Source:
NCT00942656: Not Applicable Interventional Completed Cardiovascular Disease
(2009)
Source URL:

Class (Stereo):
CHEMICAL (ACHIRAL)



Vaccenic acid (VA) (t11 octadecenoic acid) is a positional and geometric isomer of oleic acid (c9-octadecenoic acid), and is the predominant trans monoene in ruminant fats (50%–80% of total trans content). Dietary VA can be desaturated to cis-9,trans-11 conjugated linoleic acid (c9,t11-CLA) in ruminants, rodents, and humans. Hydrogenated plant oils are another source of VA in the diet, and it has been recently estimated that this source may contribute to about 13%–17% of total VA intake. In contrast to suggestions from the epidemiological studies, the majority of studies using cancer cell lines (Awad et al. 1995; Miller et al. 2003) or rodent tumors (Banni et al. 2001; Corl et al. 2003; Ip et al. 1999; Sauer et al. 2004) have demonstrated that VA reduces cell growth and (or) tumor metabolism. Animal and in vitro studies suggest that the anti-cancer properties of VA are due, in part, to the in vivo conversion of VA to c9,t11-CLA. However, several additional mechanisms for the anti-cancer effects of VA have been proposed, including changes in phosphatidylinositol hydrolysis, reduced proliferation, increased apoptosis, and inhibition of fatty acid uptake. In conclusion, although the epidemiological evidence of VA intake and cancer risk suggests a positive relationship, this is not supported by the few animal studies that have been performed. The majority of the studies suggest that any health benefit of VA may be conferred by in vivo mammalian conversion of VA to c9,t11-CLA. VA acts as a partial agonist to both peroxisome proliferator-activated receptors (PPAR)-α and PPAR-γ in vitro, with similar affinity compared to commonly known PPAR agonists. Hypolipidemic and antihypertrophic bioactivity of VA is potentially mediated via PPAR-/-dependent pathways.
Oleanolic acid or oleanic acid is a naturally occurring pentacyclic triterpenoid. It is widely distributed in food and plants where it exists as a free acid or as an aglycone of triterpenoid saponins. Oleanolic acid protects the liver from acute chemically induced liver injury, fibrosis and cirrhosis caused by chronic liver diseases. Its possess cytotoxic activity against tumor cell lines
Status:
Possibly Marketed Outside US
Source:
Canada:LINOLENIC ACID
Source URL:
First approved in 1985
Source:
Keradan by Medimetriks Pharmaceuticals, Inc.
Source URL:

Class (Stereo):
CHEMICAL (ACHIRAL)



Alpha-linolenic acid (ALA), an 18-carbon omega-3 essential fatty acid, is the precursor of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). ALA cannot be synthesized by humans and therefore must be entirely acquired from exogenous sources. Evidence for the essentiality of ALA was first provided by a study showing that ALA supplementation reversed the abnormal neurologic signs observed in a 6-year-old girl who suffered from sensory loss and visual complications. Most of the ALA is catabolized via beta-oxidation for energy generation, and a small proportion of it undergoes conversion to produce another two potent members of omega-3 PUFA family: EPA and DHA. Delta 6 desaturase (D6D) enzyme is responsible the conversion of ALA to DHA. Although not conclusive, it was suggested, that the benefits associated with ALA seem to stem mainly from EPA and DHA, and as major consequence of ALA deficiency it appears that EPA and DHA are not adequately produced.
mixture
Status:
First marketed in 1921
Source:
Lactic Acid U.S.P.
Source URL:

Class:
MIXTURE



Sodium lactate is primarily indicated as a source of bicarbonate for prevention or control of mild to moderate metabolic acidosis in patients with restricted oral intake whose oxidative processes are not seriously impaired. Sodium Lactate is most commonly associated with an E number of “E325” Sodium Lactate blends are commonly used in meat and poultry products to extend shelf life and increase food safety. They have a broad antimicrobial action and are effective at inhibiting most spoilage and pathogenic bacteria. In addition sodium lactate is used in cosmetics as a humectant, providing moisture.