COMPLETE SPECIFICATION
FIELD OF THE INVENTION
The present invention discloses a pharmaceutical combination for the treatment of spasm related GERD.
BACKGROUND OF THE INVENTION
WO 2009/114098 A2 relates to methods for treating or preventing hyper acidic disorders such as GERD or NERD using calcium receptor active compounds.
US 6420435 describes Methods of treating gastrointestinal disorders (e.g. heart bum, GERD, and gastric indigestion) comprising orally administering therapeutically effective amounts of limonene.
In US 2004/0172084 A1, GERD is treated through a method and apparatus of stimulating the body organ to accelerate a discharge of contents from the duodenum of the patient to thereby encourage discharge of contents from the stomach of the patient across the pyloric valve and into the duodenum.
WO 2004/105795 A1 relates to the combination of certain active compounds from the acid pump antagonist class and compounds, which modify gastrointestinal motility.
WO 2005/074931 relates to the combination of (S)-pantoprazole and/or its salts and compounds, which modify gastrointestinal motility.
WO 2009/145716 is directed to a pharmaceutical formulation comprising 3-Amino-2-fluoropropyl phosphinic acid or an enantiomer thereof, or a pharmaceutically and pharmacologically acceptable salt thereof, and its use for reducing paraesthesia in the treatment of GERD by administration of said compound.

OBJECTIVES OF THE INVENTION
The objective of the present invention is to provide the pharmaceutical formulation comprising a dopamine receptor antagonist and a tropane alkaloid drug with muscarinic antagonist effects.
Yet another object of the present invention is to provide an effective treatment for spasm related GERD.
Yet another object of the present invention is to provide a treatment for spasm related GERD having fewer side effects as compared to conventional treatments.
SUMMARY OF THE INVENTION
The present invention is related to a pharmaceutical composition comprising anti-psychotic drug with antispasmodic drug for the treatment of spasm related GERD. The anti-psychotic drug is preferably Levosulpiride and the anti-spasmodic drug is preferably Hyoscine butyl bromide.
DETAIL DESCRIPTION OF THE INVENTION
Spasms can happen in any muscle or muscle group. Spasm in the stomach is one of them. It is caused by involuntary contractions of the muscles in the stomach. Spasms in other muscle groups of the body are not harmful. But stomach spasms should not be neglected. This is a symptom of an underlying disease that may pose a threat to your health.
Levosulpiride is a substituted benzamide antipsychotic which is reported to be a selective antagonist of central dopamine (D-2, D-3 and D-4) receptors. Levosulpiride is also claimed to have mood elevating properties. Levosulpiride is used in the treatment of psychoses such as schizophrenia, anxiety disorders, vertigo and also in peptic ulceration.
Levosulpiride is a only a weak D2 dopamine receptor antagonist. Furthermore, in the D2 receptor family (which includes D2, D3, and D4 receptors), the affinity of levosulpiride for the D2 receptor is only 2-3 times greater than that for the D3 receptor (this contrasts with typical antipsychotics, which are 10-20 times more potent at D2 than at D3).

In consequence of the above, at low closes levosulpiride preferentially blocks dopamine autoreceptors, which are located on presynaptic neurons (this is because the dopamine autoreceptor has a greater affinity for ligands than the dopamine postsynaptic receptor, and because D3 ligands show greater preference for autoreceptors) .
In consequence of the above, low dose levosulpiride increases dopaminergic neurotransmission by increasing the presynaptic synthesis and release of dopamine (this is because it blocks the dopamine autoreceptor, which inhibits the presynaptic synthesis and release of dopamine).
In humans, low doses of levosulpiride generally refer to doses of 50-200 mg/day. At these doses, levosulpiride is therapeutic for negative and cognitive symptoms of schizophrenia, and for depressive and somatoform disorders.
In high doses, levosulpiride also blocks D2 dopamine postsynaptic receptors. The result is decreased dopaminergic neurotransmission. In humans, high doses of levosulpiride generally refer to doses of 400-800 mg/day. At these doses, levosulpiride is therapeutic for positive symptom schizophrenia.
Levosulpiride down regulates cortical beta adrenoceptors. This action may contribute to the antidepressant action of the drug.
Levosulpiride does not block 5-HT2 serotonergic and HI histaminic receptors. Therefore, it is unlikely to occasion adverse effects such as sedation, increased appetite, and increased weight.
Levosulpiride does not block alpha-1 adrenergic receptors, and is therefore unlikely to cause postural hypotension.
Levosulpiride does not block muscarinic cholinergic receptors, and is therefore unlikely to cause adverse effects such as dry mouth, blurred vision, impaired accommodation, constipation, and difficulty in passing urine.

In low doses (50-200 mg/day), levosulpiride blocks dopamine autoreceptors and may therefore be effective for the negative and cognitive symptoms of schizophrenia, and for depressive and somatoform disorders.
In high doses (400-800 mg/day), levosulpiride blocks dopamine postsynaptic receptors, and may therefore be effective for the positive symptoms of schizophrenia.
Levosulpiride does not bind to 5-HT2, HI, alpha-1, muscarinic, and other receptors, and is therefore unlikely to be associated with sedation, increased appetite and weight, postural hypotension, dry mouth, constipation, and other adverse effects related to antagonism at these receptor sites.
Hyoscine Butyl bromide is specifically indicated for the treatment of bladder or intestinal spasms. It has been used in the treatment of irritable bowel syndromes and other gastro-intestinal conditions, as well as the immediate treatment of gastro-intestinal distress and secondary to numerous other medications in the treatment of cancer.
Hyoscine Butyl bromide is an anti-spasmodic medication often used in the treatment of irritable bowel syndrome. It acts to block the action of acetylcholine at parasympathetic sites in smooth muscle and in secretory glands, stopping spasms in these areas.
Abdominal pain is one of the primary reasons people seek medical attention in a year, many of which are caused by spasms of intra-abdominal organs. Hyoscine Butyl bromide acts to stop the spasms in these areas, decreasing pain and discomfort and promoting proper organ function.
It's been used in the treatment of irritable bowel syndrome, bladder spasms, colicky abdominal pain, dysmenorrheal and in association with other medications in the treatment of late stage cancer patients. It is also used to assist in a colonoscopy and sigmoidoscopy and may help manage renal colic.

In the present invention, the anti-psychotic drug is preferably Levosulpiride which is present in the range of 10 mg to 40 mg, and the anti-spasmodic drug is preferably Hyoscine butyl bromide present in the range of 10 mg to 40 mg.
The release of both the said active ingredients from the pharmaceutical formulations of the present invention can be immediate or modified, controlled, delayed, sustained, and extended. The release rate for both active drugs can be the same or different.
The pharmaceutical formulations of the present invention may comprise formed particles with the same composition or formed particles with different composition and different release rate of said active ingredients.
The present invention can be formulated, but not limited to, in the following manner-
The present invention can be formulated, but not limited to, in the following manner.
Following ingredients are weight accurately for tablet (1000 Tablets)-

For coating material-

1) The following materials are taken, dried and sifted-

2) BINDER PREPARATION: NON AQUEOUS
Dissolve 4 gm PVPK-30 in 60 ml isopropyl alcohol with stirring.
3) WET MIXING
Pour the binder in the RMG containing dried mixed material and mix for 10 minutes. Add 20 ml Isopropyl alcohol if required.
4) WET MILLING
Pass the wet mass using # 8 manually.

5) PRYING
Dry the wet miled material in tray drier at a temperature 40-50° C for 90 minutes to get the moisture content between 2%-3%.
6) SIFTING
Sift the dried granules through sieve # 24.
7) LUBRICATION
Take dried granules of step 6, to it add sieved material of the following table and mixed manually in PP bags

8) COMPRESSION
Compress the lubricated granules using required dies and punches. Process for film coating


Mix the above ingredients in partial quantity of isopropyl alcohol and PEG-6000. Mix the above solution in methylene chloride. Now add the mixture in the remaining quantity of Isopropyl alcohol. Stir the solution with the help of stirrer. After that add red oxide of iron in this solution and stir the solution for 10 minutes. Pass the above solution through # 200. The solution so obtained is used for film coating

CLAIMS
1. A pharmaceutical formulation comprising Levosulpiride and Hyoscine
butyl bromide wherein Levosulpiride is present in the range of 10 mg to
40 mg, and the Hyoscine butyl bromide is present in the range of 10 mg
to 40 mg. along with pharmaceutically acceptable excipients; useful for
the treatment of spasm related GERD.
2. The pharmaceutically acceptable excipients as claimed in claim 1 are
selected from diluents, binding agents, disintegrants, and lubricants.
3. The diluents as claimed in claim 2 can be selected from lactose, sucrose,
glucose, mannitol, sorbitol, calcium carbonate, and magnesium stearate.
4. The binding agents as claimed in claim 2 can be selected from polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), xylitol, sorbitol and maltitol which are mixed with the appropriate solvent.
5. The solvent as claimed in claim 4 can be selected from purified water or isopropyl alcbhol or the mixture of both.
6. The disintegrants as claimed in claim 2 can be selected from
polyvinylpyrrolidone (crospovidone), crosslinked sodium carboxymethyl
cellulose (croscarmellose sodium) and sodium starch glycolate.
7. The lubricants as claimed in claim 2 can be selected from talc or silica,
and fats, e.g. vegetable stearin, magnesium stearate or stearic acid.
8. The formulation as claimed in claim 1 can be coated with Hydroxypropyl
Methyl Cellulose, along with suitable plasticizer, opacifier, coloring agent
and the solvent.