DESCRIPTION
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.
US 4126672 disclose sustained release pharmaceutical capsules suitable for
oral administration and particularly suitable for sustained release therapy with
certain benzodiazepines, e.g. chlordiazepoxide and diazepam. The formulation
contained in the disclosed capsules is hydrodynamically balanced to be
buoyant in gastric fluid thereby remaining buoyant in the gastric fluid until
substantially all of the medicament therein has been released.

OBJECTIVES OF THE INVENTION
The objective of the present invention is to provide the pharmaceutical formulation comprising a benzodiazepine derivative having sedative/hypnotic effect 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 a benzodiazepine derivative having sedative/hypnotic effect with antispasmodic drug for the treatment of spasm related GERD. The benzodiazepine derivative having sedative/hypnotic effect is preferably Chlordiazepoxide 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.
Chlordiazepoxide possesses sedative, hypnotic, anxiolytic and muscle relaxant properties. These effects appear to be mediated through facilitation of the actions of gamma aminobutyric acid (GABA) in the CNS. Chlordiazepoxide acts selectively on polysynaptic neuronal pathways and may inhibit or augment transmission, depending on the endogenous function of GABA. It does not produce ganglionic blockade or reduce affective responses at therapeutic dosage as do phenothiazine drugs and reserpine. Amine oxidase inhibition has not been demonstrated with chlordiazepoxide.
Following oral administration, the drug appears in the blood stream in 0.5 to 1 hour; peak blood levels occur in 2 to 4 hours. Chlordiazepoxide has a volume of distribution of 0.3 L/kg and is 96% protein bound. The plasma half-life of a single dose of chlordiazepoxide in healthy subjects has been reported to range from 5 to 30 hours. Pharmacologically active metabolites of chlordiazepoxide

include desmethylchlordiazepoxide, demoxepam, desmethyldiazepam and
oxazepam. Less than 1% is excreted in the urine unchanged.
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, dysmenorrhea! 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 benzodiazepine derivative having
sedative/hypnotic effect is Chlordiazepoxide which is present in the range of 1
mg to 15 mg, preferably 5 mg and the anti-spasmodic drug is preferably
Hyoscine butyl bromide present in the range of 10 mg to 40 mg preferably 20
mg.
The formed particles, prepared with using the suitable excipients, are suitable
for the preparation of multiple unit forms such as capsules or tablets with the
primary formed particles wherein a multiple unit form disintegrates to individual
primary formed particles from which the active substance is released.
The release of Chlordiazepoxide and Hyoscine 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 Chlordiazepoxide and Hyoscine. The present invention also relates to the process for the preparation of the formed particles regular and irregular in shape. They are prepared by the wet granulation with organic solvent. For granulation either a solvent or binder dispersion in an organic solvent may be used.
The formulation can be manufactured by the suitable procedure that are already been described in the prior art for manufacturing tablets or other suitable dosage forms.

CLAIMS
1. A pharmaceutical formulation comprising 1 mg to 15 mg of
Chlordiazepoxide, preferably 5 mg, and pharmaceutically acceptable
salts of hyoscine preferably Hyoscine butyl bromide 10 mg to 40 mg,
preferably 20 mg, along with pharmaceutically acceptable excipients.
2. The pharmaceutically acceptable excipients claimed in 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), Hydroxy propyl cellulose, 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 alcohol 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.