VASCULERA - diosmin and calcium magnesium potassium carbonate chloride hydroxide tablet
Primus Pharmaceuticals, Inc.
DESCRIPTION
VASCULERA (diosmiplex) consists of a specially formulated proprietary blend of micronized, highly purified diosmin glycoside in combination with alkaline granules, alka4-complex. Diosmin glycoside manages venous inflammation, accumulation of polymorphonuclear leukocytes, platelets and other thrombotic components as well as edema, caused by a deterioration of venous vessel walls. Alka4-complex works by buffering stomach acid and managing blood pH to affect local metabolic acidosis in veins.
Diosmin Glycoside
Each VASCULERA tablet contains 600 mg of diosmin glycoside (diosmin), a micronized, highly purified flavonoid fraction (from citrus) with hesperidoside constituents. In clinical trials, this level of intake has been shown to manage chronic venous insufficiency (CVI). Diosmin is chemically described as (7-[[6-O-(6-Deoxy-α-L-mannopyranosyl)-�-D-glucopyranosyl]oxy]-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-4H-1-benzopyran-4-one) with a molecular weight of 608.5. The empirical formula for diosmin is C28 H32 O15
Alka4-complex
Each VASCULERA tablet contains 30 mg of a proprietary, structured, highly alkaline agglomeration of reactive magnesium hydroxide (Mg(OH)2 , molecular weight 58.3), potassium chloride (KCl, molecular weight 74.6) and potassium hydroxide (KOH, molecular weight 56.1) held apart from each other in a matrix of calcium carbonate (CaCO3 , molecular weight 100.1), microcrystalline cellulose and croscarmellose sodium.
Other Ingredients
VASCULERA contains the following other ingredients as fillers and excipients: microcrystalline cellulose, stearic acid, croscarmellose sodium, povidone, silicone dioxide, and water. Tablets do not contain fructose, glucose, sucrose, lactose, gluten, maltodextrin, tree nuts, peanuts, or flavors. VASCULERA is suitable for vegans.
Medical Food
The U.S. Congress defined "medical food" in the Orphan Drug Act and Amendments of 1988 as "a food which is formulated to be consumed or administered enterally under the supervision of a physician, and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation." VASCULERA has been developed, manufactured and labeled in accordance with the statutory definition of a medical food. VASCULERA is to be used only under a physician's supervision.
Generally Recognized As Safe
The ingredients in VASCULERA are Generally Recognized as Safe (GRAS). This is the statutory U.S. safety standard that the U.S. Food and Drug Administration (FDA) requires of all ingredients added to food products. The standard for an ingredient to achieve GRAS status requires technical demonstration of non-toxicity and safety, general recognition of safety through widespread usage and agreement of that safety by experts in the field.
CHRONIC VENOUS INSUFFICIENCY (CVI)
Chronic venous insufficiency is caused by venous hypertension (VH). VH, in turn, aggravates these metabolic imbalances leading to a self perpetuating cycle of further metabolic changes, including venous acidosis. These changes promote further inflammation in vascular tissue leading to edema, skin damage and possible ulceration and deep vein thrombosis (DVT). Varicose veins and hemorrhoids are also part of the spectrum of CVI disorders.
CLINICAL PHARMACOLOGY
Mechanism of Action
VASCULERA acts by restoring toward normal the metabolic aspects of CVI including modulation of venous tone and capillary resistance, management of lymphatic drainage, and inflammation in the microcirculation. Preclinical and clinical data suggest that the diosmin glycoside in VASCULERA manages venous tone by increasing smooth muscle contractibility. In addition, diosmin has been shown to decrease edema by increasing lymphatic contractility and drainage. Finally, diosmin manages the oxidative and inflammatory factors induced by VH. Alka4-complex has been shown in preclinical and clinical studies to act as an acid buffering agent in the gut and to counteract the effects of increased acid production systemically.
Diosmin Glycoside
The diosmin in VASCULERA has been shown in both cell and animal models to enhance venous tone by prolonging the post-synaptic response to norepinephrine (NE) and increasing the sensitivity of vascular smooth muscle to NE and calcium, even under conditions of acidosis. Diosmin inhibits the NE degrading enzyme catechol-O-methyltransferase (COMT). Diosmin has also been shown to manage lymphatic drainage and decrease edema by increasing lymphatic vessel contraction frequency and amplitude. Venous hypertension induces production of inflammatory factors such as prostaglandins and leukotrienes, metalloproteinaises, cytokines, adhesion molecules, and VEGF. Localization of inflammatory cells generates high levels of tissue destructive reactive oxygen species (ROS). Diosmin acts as a scavenger of ROS, inhibits 5-lipoxygenase and the production of prostaglandins E2 and thromboxane B2, which may help to protect endothelial cells from damage associated with inlammation and acute oxidative stress.
Alka4-complex
Clinical studies have shown that alka4-complex in VASCULERA can reduce acidosis under extreme exercise loads. The specially agglomerated matrix of alka4-complex has been shown to resist neutralization by acid solutions. This ability to survive the acid environment of the stomach and to be taken up in the intestine may account for its effect on blood pH during exercise. Alka4-complex may counter the local acidosis produced in CVI and work synergystically with diosmin to manage venous inflammtion. In addition, the alka4-complex has been shown to reduce the acid producing effects of certain foods by buffering the acidity in the gastrointestinal tract, while allowing a sufficient portion of the complex to survive in the stomach, and is absorbed in the small intestine thereby being available to manage mild acidosis.
METABOLISM
Diosmin glycoside
Diosmin is hydrolyzed to its aglycone form, diosmetin, by intestinal microorganisms and enzymes in the intestinal lumen prior to absorption. Once it reaches the liver, diosmetin is extensively glucuronidated before entering the systemic circulation. Diosmetin may also be reduced to its corresponding flavanone aglycone, hesperetin, by intestinal bacteria in second pass metabolism. No diosmin is detected in the serum in animals or humans. Only the active form diosmetin, is detected after �-glucoronidase digestion. The phenolic acid products of diosmetin degradation are excreted in the urine, while unabsorbed/unmetabolized diosmin and diosmetin are excreted in the feces.
Alka4-complex
In contrast to sodium bicarbonate, alka4-complex has been shown in acid dissolution studies to release alkalizing salts in two gradual steps. Starting at a pH of 2, alka4-complex takes approximately 15 min to raise the solution pH to 6 whereas this occurs in seconds with bicarbonate. A further increase to a pH of 7 occurs over the next 60-90 min period. This biphasic, slow release characteristic gives alka4-complex seven times more pH neutralizing capacity compared to the same concentration of sodium bicarbonate. The molecular protection afforded by the proprietary matrix allows the alka4-complex to enter the intestinal tract where it is absorbed. Compared to bicarbonate ions, hydroxyl ions present in alka4-complex have been shown to be better absorbed by the intestional lumen.
Vasculera Indications and Usage
Indications
VASCULERA is indicated for the clinical dietary management of the metabolic processes associated with chronic venous insufficiency (CVI). Conditions which occur due to CVI include varicose veins, spider veins, edema, deep vein thrombosis, stasis dermatitis, venous ulcers and hemorrhoids. Symptoms of CVI include heavy leg syndrome (dull aching discomfort, heaviness, cramping, itching and tingling in legs), pain that gets worse when standing, pain that gets better when legs are raised, swelling of the legs (edema), redness of the legs and ankles, skin color changes around the ankles and thickening of the skin on the legs and ankles (stasis dermatitis). VASCULERA must be used under the supervision of a physician.
Usage
VASCULERA should be taken as directed by a physician. See Dosage and Administration for additional information.
Interactions with Food
VASCULERA can be taken with or without food.
PRODUCT ADMINISTRATION
The recommended intake of VASCULERA (diosmiplex) is 1 tablet per day for the dietary management of Chronic Venous Insufficiency (CVI), manifested as: varicose/spider veins, edema, stasis dermatitis and or venous ulcers. Results may not be seen for 4 to 8 weeks. For venous ulcers, results may not be seen for several months.
For CVI manifested as hemorrhoidal disease, the recommended initial intake is 1 tablet 3 times daily for 4 days followed by 1 tablet twice daily for 9 days, or as directed by a physician. For hemorrhoidal discomfort persisting after resolution of the acute flare or for recurrent hemorrhoidal flares irrespective of persisting discomfort, a maintenance intake of 600 mg of Vasculera daily is recommended.
HOW SUPPLIED
VASCULERA is a grayish-yellow oblong tablet with white flecks on the surface.
The tablets are packaged in unit-of-use blister packages :
68040-610-14 contents 30 tablets per carton (30-day supply)
68040-610-10 contents 15 tablets per carton (15-day supply sample)68040-610-25 contents 3 tablets per carton (3-day supply sample)
Storage
Store at room temperature 59� � 86�F (15� � 30�C). Protect from light and moisture. Store tablets in original carton until usage. Keep out of reach of children.
