COMPLETE SPECIFICATION
Filed of the Invention
The invention is related to the field of pharmaceuticals. More in particular, the present invention is related to the pharmaceutical composition comprising at least a statin, with Ubiquinone having greater bioavailability.
Related Prior Art For The Invention
US2009137617 (A1) discloses methods and compositions for the treatment of cardiovascular disorders. Specifically, the invention is directed to compositions comprising vitamin E, statins and/or glutathione peroxidase mimetics; methods of treating diabetic patients expressing the Hp-2-2 haptoglobin genotype; a method of inhibiting or suppressing a cardiovascular disorder in a diabetic subject, treating cardiovascular disease in subjects exhibiting the Haptoglobin Hp-2-2 genotype; and methods of treating cardiovascular disease in subjects exhibiting the Haptoglobin Hp-2-2 genotype.
US2006052437 (A1) relates to the therapeutical combination of an HMG-CoA reductase inhibitor (statin) and a nitrate ester and is useful mainly for the preparation of medicaments for the prevention and treatment of coronary diseases as myocardial infarction and cerebrovascular diseases as stroke. Particularly, as a nitrate ester, a nitrate prodrug of aspirin, salicylic acid or vitamin E is used. Said compositions, compared to single components, have the advantages to be without toxic effects, mainly due to statins, and to be more effective.
DE202004009305 (U1) provides the detailed information for dietetic oral supplements, e.g. capsules or tablets, for people with
physiological deficiency symptoms, especially undergoing therapy with HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors (statins), leading to reduction of cell internal energy recovery, the formulations contain 10-1000 mg/take of coenzyme Q10, in combination with other physiologically active substance(s) to assist cellular energy recovery. An independent claim is also included for dietetic formulations containing components, in concentrations of 0-1000 mg/take, as follows: (1) thiamin (vitamin B1); (2) niacin or nicotinic acid or nicotinamide; (3) riboflavin (vitamin B2) or riboflavin 5'-phosphate (sodium salt); (4) L-carnitine.
US2004018248 (A1) provides a composition for oral administration comprising a mixture of a statin, docosahexaenoic acid "DHA", vitamin E, vitamin C, vitamin B6, vitamin B12, folic acid, and calcium together with a suitable carrier. These compositions are particularly useful as dietary supplements administered to reduce the risk factors of cardiovascular disease, such as elevated serum cholesterol levels and high blood pressure.
NZ526069 (A) discloses are combinations of uridine and biological precursors of uridine and compounds of formula (I) wherein R1 is selected from H or alkyl; R2 and R3 are each independently selected from H, OH, alkyl, alkoxy, alkenyl, alkenoxy or alkynoxy; and R4 is alkyl, alkenyl, alkoxy, alkenoxy, alkylol or alkenylol. A preferred compound of formula (I) is Coenzyme Q10. Combinations as described above are useful in the treatment of the side effects of statin therapy, in particular muscle pain. Also disclosed is the use of said combinations for the treatment of muscle pain or fatigue not related to the use of statins.
US patent 4929437 discloses the composition and method of counteracting HMG-CoA reductase inhibitor-associated elevated transaminase levels. The method comprises the adjunct administration of an effective amount of a HMG-CoA reductase inhibitor and an effective amount of Coenzyme Q.sub. 10.
Objectives of the Invention
The objective of the present invention is to provide a pharmaceutical formulation providing the treatment of hypercholesterolemia, and constitute an important part of comprehensive strategies for the treatment of cardiovascular disease.
Another objective of the present invention is to provide a pharmaceutical formulation which lowers the side effects of statin drugs, apart from delivering statins.
Yet another objective of the present formulation is to reduce the negative physiologic side effects of cholesterol lowering medications.
Yet another object of the invention is to make greater bioavailability of Ubiquinone.
Detailed description of the invention
The present invention is,directed at combinations comprise an HMG CoA reductase inhibitor medicament in combination with Ubiquinone having greater bioavailability. HMG CoA reductase inhibitors such as cerivastatin, fluvastatin, atorvastatin, lovastatin, pravastatin, simvastatin reduce serum cholesterol. However, an unfortunate side effect is that they also simultaneously reduce serum Ubiquinone levels.
In the past, the administration of statin drugs was well known to cause a rapid decline in the body's stores of Ubiquinone. Ubiquinone has been called, "The most vital nutrient" because its presence is needed for energy production in all of your cells. Cells which need a lot of energy, such as heart cells, are most sensitive to this depletion. Muscle pain and other vital organ dysfunction can be related to reduce Ubiquinone levels.
It was found out through research that the addition of fatty acids with Ubiquinone increases the absorption of Ubiquinone. The absorption of Ubiquinone is very low and also more the amount less will be the absorption.
The pharmaceutical composition, according to the present invention, comprises of Statin drugs, and more bioavailable Ubiquinone.
The statin drugs may include cerivastatin, fluvastatin, atorvastatin, lovastatin, pravastatin, or simvastatin, preferably atorvastatin.
The fatty acids may include Butyric acid, Laurie acid, Myristic acid, Palmitic acid, and Stearic acid preferably stearic acid.
The dosage form for the above pharmaceutical composition may be oral dosage formulations. The oral dosage formulation may be tablets, capsules, sachets etc.
Atorvastatin or its pharmaceutically acceptable salts are in the range of 5 mg to 80 mg, whereas Ubidecarenone is present in the range 40 mg to 200 mg.
Suitable fillers may be microcrystalline cellulose, powdered cellulose, lactose, starch, pregelatinized starch, or sucrose preferably microcrystalline cellulose and lactose.
Suitable binders are starch, polyvinylpyrrolidone, alginic acid, methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polymethacrylates, and others preferably hydroxypropyl cellulose, hydroxypropyl methylcellulose and polyvinylpyrrolidone.
Suitable disintegrants are starch, pregelatinized starch, sodium starch glycolate, sodium carboxymethylcellulose, cross-linked sodium carboxymethylcellulose, cross-linked polyvinylpyrrolidone, alginic acid, sodium alginate, and others preferably sodium starch glycolate, cross-linked sodium carboxymethylcellulose and cross-linked polyvinylpyrrolidone.
Suitable glidants are magnesium stearate, calcium stearate, aluminium stearate, stearic acid, palmitic acid, cetanol, stearol, colloidal silicon dioxide, talc, powdered cellulose, starch and others, preferably, colloidal silicon dioxide.
Suitable lubricants are stearic acid, calcium, magnesium, zinc or aluminium stearate, siliconized talc, glycerol monostearate, and others. Preferred lubricants are calcium or magnesium stearate and stearic acid.
The release of the ingredients from the pharmaceutical formulations of the present invention can be immediate or modified, controlled, delayed, sustained, and extended. The release rate for the active drugs can be the same or different.
The present invention can be formulated, but not limited to, in the following manner.
(Table Removed)
1) Weigh the following materials and pass them according to the
following sieve number-
(Table Removed)
2) Sift the Ubidecarenone through sieve # 40 and BHA and BHT through sieve # 80. Granulate Ubidecarenone, BHA and BHT with ethyl cellulose, isopropyl alcohol and methylene chloride and pass it through sieve # 30. Air dry sifted material for 6 hours.
3) Take sifted material of step 1) and 2) and transfer them in p.p. bag for 10 minutes.
4) Dissolve 12.5 gm of polyvinyl pyrrolidone and dissolve it in 100 ml purified water.
5) Pour the binder in the dried mixed material obtained in step 3. Add 20 ml water to the mixed material. Do the wet mixing manually for 10 minutes.
6) Pass the wet mass through sieve # 8.
7) Dry the granules obtained in step in FBD at 45° for 3 hours.
8) Sift the dry granules of step through sieve # 24. Collect the sifted granules in clean containers.
9) Take the dried granules obtained after sieving, and add it to the following sieved material in PP bags for 10 minutes.
(Table Removed)
10) Compress the above granules to form a tablet.
11) The compressed tablet can be coated with the help of following coating material-
Film Coating
Seal Coating
(Table Removed)

CLAIMS
1) A pharmaceutical formulation comprising Atorvastatin or its pharmaceutically acceptable salts in the range of 5 mg to 80 mg and Ubidecarenone in the range 40 mg to 200 mg with a bioavailability enhancer along with pharmaceutically acceptable excipients.
2) The bioavailability enhancer as claimed in claim 1 may be Butyric acid, Lauric acid, Myristic acid, Palmitic acid, and Stearic acid preferably stearic acid.
3) The pharmaceutically acceptable excipients are selected from diluents, binding agents, disintegrants, and lubricants.
4) The diluents as claimed in claim 3 can be selected from lactose, sucrose, glucose, mannitol, sorbitol, calcium carbonate, and magnesium stearate.
5) The binding agents as claimed in claim 3 can be selected from polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), xylitol, sorbitol and maltitol which are mixed with the appropriate solvent.
6) The solvent as claimed in claim 5 can be selected from purified water or isopropyl alcohol or the mixture of both.
7) The disintegrants as claimed in claim 3 can be selected from polyvinylpyrrolidone (crospovidone), crosslinked sodium carboxymethyl cellulose (croscarmellose sodium) and sodium starch glycolate.
8) The lubricants as claimed in claim 3 can be selected from talc or silica, and fats, e.g. vegetable stearin, magnesium stearate or stearic acid.

9) The formulation as claimed in claim 1 can be coated with Hydroxypropyl Methyl Cellulose, along with suitable plasticizer, opacifier, coloring agent and the solvent.
10) The formulation as claimed in claim 1 can be oral or injectable, preferably oral.