FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
PATENTS RULES, 2003
(COMPLETE SPECIFICATION)
TITLE OF INVENTION - "MUSCLE RELAXANT COMPACT DOSAGE FORM." NAME OF APPLICANT - ZOTA HEALTH CARE LTD
ADDRESS OF APPLICANT- ZOTA HEALTH CARE LTD
ZOTA HOUSE
2/896, HIRA MODI STREET, SAGRAMPURA SURAT 395002 (GUJARAT) INDIA.
The following specification particularly describes the nature of the invention and the manner in which it is to be performed.

FIELD OF INVENTION
The present invention relates to colchicine derivatives, in particular Colchicoside with muscle relaxant, anti-inflammatory activity.
BACKGROUND OF THE INVENTION
Muscle relaxant drugs reduce muscle tone and are used in therapy for the treatment of contractures and muscle spasm. Muscle spasm is one of the main factors responsible for chronic pain; it characterises several pathologies of the locomotor apparatus as well as inflammatory-rheumatic and degenerative orthopaedic pathologies; when it affects articulations, further to pain, it causes rigidity, which reduces joint mobility and flexibility in the affected part. For these reasons, the study of molecules endowed with muscle relaxant and antispasmodic properties still raises remarkable clinical interest.
The activity of colchicoside is due to its ability to interact with strychnine-sensitive glycine receptors; therefore, compounds having glycine-mimicking activity can be used in the rheumatologic-orthopaedic field, due to their muscle relaxant properties.
Colchicoside (CC) IUPAC Name: N-[l,2,10-trimethoxy-9-oxo-3-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yI]oxy-6,7-dihydro-5H-benzo[a]heptalen-7-yl]acetamide is used clinically for its muscle relaxant, anti-inflammatory, and analgesic properties, and it has been shown to interact with gamma-aminobutyric acid (GABA) type A receptors (GABAARs) and strychnine-sensitive glycine receptors in the rat central nervous system. In contrast to a proposed agonistic action at these two types of inhibitory receptors, pharmacological evidence has shown that, under certain conditions, TCC manifests convulsant activity in animals and humans.
In Patent application number: 20080279933 wherein this invention is a novel pharmaceutical composition comprising flurbiprofen or a pharmaceutically acceptable salt thereof in combination with an a-2 adrenergic receptor agonist or a gamma-aminobutiric acid receptor agonist with anti-inflammatory, analgesic and myorelaxant activity.

US 2007/0116729 Al wherein A lyophilization process which comprises dissolving a material in one or more solvents for said material to form a solution; forcing said material at least partially out of solution by combining the solution and a non-solvent for the material, which non-solvent is miscible with the solvent or solvents used and wherein said non-solvent is volatilizable under freeze-drying conditions. In addition, for hydrophobic and/or lipophilic materials, the anti-solvent can be omitted, and the solution of the material in the solvent can be subjected directly to freeze drying. The lyophilizates can then be reconstituted with typical aqueous diluents in the case of hydrophilic materials. Hydrophobic and or lipophilic materials can be initially reconstituted with propylene glycol and/or polyethyleneglycol to form a high concentration solution therein and this is further diluted for use with a diluent of Intralipid,
SUMMARY OF THE INVENTION
To overcome problems as set forth above, in one aspect of the invention is a pharmaceutical composition contains a combination of a non steroidal anti inflammatory drug and colchicoside, both active ingredients being present in the composition.
Another object of the present invention is a pharmaceutical composition are preferably made so as to be administered by the oral, parenteral route, injactable (IV & IM) ,local Spray, gel, aeroburn gel dressing or self adhesive bandage which comprises gel.
The present invention has the advantage to provide a stable combination product providing superior analgesic, anti inflammatory and muscle relaxant property compared to plain colchicoside tablets.
The pharmaceutical composition and its formulation process involve avoiding chemical interaction of thiocolchicoside with zaltoprofen using pharmaceutically acceptable excipients in the dosage form.
The dose and frequency of administration of the medicament of the present invention are not particularly limited, and they may be appropriately chosen depending on conditions such as the body weight or age of a patient, severity and the like.

According to another of its objects, the present invention relates to the use of a composition ' as previously described, for the preparation of a medicament intended for ameliorating and/or treating musculoskeletal and joint disorders such as ankylosing spondylitis, low back pain, osteoarthritis, and rheumatoid arthritis, and peri-articular disorders such as bursitis and tendonitis, and painful muscle spasm such as cervical spondylitis, lumbago thereof.
A further object of the present invention is compact dosage form for treating the pathologies indicated above, which comprises the administration to a patient of an effective amount of the composition according to the invention.
In another aspect of the invention, that it has less side effects because all the substance as comparative to existing drug which is toxic and expensive and not 100% effective too.
These and other features, aspects and advantages of the present invention will become better understood with reference to the following description and claims.

DETAILED DESCRIPTION OF THE INVENTION
The invention will now be described in detail in connection with certain preferred and optional embodiments. So that various aspects thereof may be more fully understood and appreciated.
According to proffered embodiment, that this product contains active ingredients Thiocolchicoside and Zaltoprofen along with other excipients
According to proffered embodiment Thiocolchicoside is a muscle-relaxant (skeletal) agent used for the treatment of orthopaedic, traumatic and rheumatologic disorders. In the treatment of painful muscle spasms. Muscle relaxant Thiocolchicoside acts both in contractures of central origin and in those of reflex type, rheumatic and traumatic. Spastic sequelae of hemiparesis, Parkinson's disease and Iatrogenic Parkinson symptoms, particularly the neurodyslectic syndrome. Acute and chronic lumbar and sciatic pain, cervico-brachial neuralgia, persistent torticollis, post-traumatic and post-operative pain.
Thiocolchicoside (C27H33N011) is useful for the treatment of those disorders like, low back pain (LBP) is a very common painful musculoskeletal disorder that affects virtually everyone at some time during their life, and has a lifetime prevalence ranging from 58% to 84%. Low back problems rank high among the reasons for physician office visits and are costly in terms of medical treatment, loss productivity, and non monetary costs such as diminished ability to perform or enjoy usual. In fact, activities for people under age 45, low back problems are the most common cause of disabilities such as Post-traumatic pain - severe sprains, strains, contusions, fractures etc. post accidents & severe injuries, Ankylosing Spondylitis and Acute Lumbago - mild to severe pain in the lower back , Dysmenorrhoea pain experienced by women during menstrual period, with no medical problem.Commonly affects teenagers & young women.
Post-episiotomy pain wherein episiotomy is an incision into the perineum (area of skin between the vagina and the anus).
Some skeletal muscle spasms such as Carpopedal spasm , Clonic (rhythmic) spasm ,FaciaI spasm, Intention spasm ,Myopathic spasm ,Saltatory spasm ,Tetanic spasm, Toxic spasm, Fibromyalgia (FM)

Spasm associated with inflammatory conditions such as arthritis, sprains, strains, low back pain, dental procedures, dysmenorrhoea, and dermal inflammatory conditions.
Though, pain and inflammation are certainly of a necessary diagnostic value, once that role is accomplished, continued presence of pain and inflammation is unpleasant in nature besides hampers mobility; hence should be treated and relieved off. NSAlDs are commonly used to combat inflammation (with or without supplementary analgesics). Wide varieties of NSAIDs are available in the market.
Most NSAIDs exert their action by inhibiting prostaglandins only and have no action on other pain mediators like Histamine and Bradykinin.
For Symptomatic relief of low back pain, non-steroidal ami -inflammatory drugs ( NSAIDs) and analgesics are often in used in combination with muscle relaxants. However adverse effects, especially sedation, limit the use of some muscle relaxants.
Thiocolchicoside is a non-sedating muscle relaxant that has been shown to be safe and effective as monotherapy in the treatment of above problems. The present study was carried out to determine if the combination of thiocolchicoside and standard treatment is more effective than standard treatment alone.
The major anti-inflammatory effect is due to inhibition of PG synthesis. At high concentration, it also inhibits lipo- oxygenase and thus inhibit formation of leucotrienes. Thiocolchicoside may inhibit migration of leucocytes into inflammatory sites.
As per the Pharmacological Study and Mechanism of action is that Thiocolchicoside, a semisynthetic derivative of the naturally occurring compound colchicoside with a relaxant effect on skeletal muscle, has been found to displace both gamma-amino butyric acid (GABA) and strychnine binding, suggesting an interaction with both GABA and strychnine-sensitive glycine receptors.
Thiocolchicoside is a muscle relaxant that has been claimed to possess GABA-mimetic and glycinergic actions. In acts on inhibitory GABA and strychnine-sensitive glycine receptors in brain γ-Aminobutyric acid (Gamma Aminobutyric acid GABA) is the chief inhibitory neurotransmitter in the central nervous system. Activation of GABA receptors reduces neuronal excitability throughout the nervous system and increases the threshold value for muscle contraction. GABAergic action is directly responsible for the reduction of muscle

tone and muscle spasm and causes muscle relaxation. Thiocolchicoside also blocks the pain sensations causing analgesic effect
According to proffered embodiment Zaltoprofen or (C17-H14-03-S) a preferential COX-2 inhibitor, however, other COX-2 preferential inhibitors such as meloxicam and etodolac did not exhibit any apparent action, and also, preferential COX-1 inhibitors mofezolac and indomethacin, COX-1 and COX-2 inhibitor loxoprofen sodium showed a weak effect. These non-steroidal anti-inflammatory drugs (NSAIDs) except for zaltoprofen strongly inhibited an acetic acid-induced writhing response related to PGs based on COX-1, at lower doses.
Zaltoprofen (ZLT) is a non-steroidal anti-inflammatory drug, and has excellent effects even on post-surgery or post-trauma chronic inflammation. The chemical name of ZLT is (±)-2-(10,11-dihydro-10-oxodibenzo [b,f] thiepin-2-yl) propionic acid. ZLT selectively inhibits cyclooxygenase-2 activity and prostaglandin E2 production. It is used in the treatment of rheumatoid arthritis, osteoarthritis, and other chronic inflammatory Pain conditions. ZLT is a unique compound that also has anti-bradykinin activity. It is not only of cyclooxygenases but also of bradykinin-induced 12-lipoxygenase inhibitors.
Zaltoprofen had a moderate inhibitory effect compared with those of the above-mentioned NSAIDs. Zaltoprofen produces an analgesic action on bradykinin-induced nociceptive responses by blocking the B(2) receptor-mediated pathway in the primary sensory neurons. Zaltoprofen may serve as a potent and superior analgesic for the treatment of pain.
The pharmaceutical composition according to the present invention can further include others active ingredients having an acceptable pharmaceutical activity.
As per the Pharmacological Study, a new NSAID of the propionic acid derivative has shown good analgesic and anti-inflammatory activity in several clinical trials with efficacy as good as some of the comparative drugs - indomethicn, ketoprofen
The mechanism of action is that it's an effective Antipyretic and Analgesic.
These compositions are preferably made so as to be administered by the oral, parenteral route, injactable (IV & IM), local Spray, gel, aeroburn gel dressing or self adhesive bandage which comprises gel.
For example, in the form of pharmaceutical compositions for oral administration such as granules, fine granules, powders, hard capsules, soft capsules, syrups, emulsions,

suspensions, solutions and the like, or in the form for sublingual a buccal administration, or in the form of pharmaceutical compositions for parenteral administrations such as injections for intravenous, intramuscular, or subcutaneous administration, drip infusions, transdermal preparations, transmucosal preparations, nasal drops, inhalants, suppositories and the like (Local spray) Injections or drip infusions may be prepared as powdery preparations such as in the form of lyophilized preparations, and may be used by dissolving just before use in an appropriate aqueous medium such as physiological saline. Sustained-release preparations such as those coated with a polymer may be directly administered intracerebrally.
The tablets can be coated with sucrose or other appropriate materials or alternatively they can be treated such that they have a prolonged or delayed activity and that they continuously liberate a predetermined quantity of active ingredient.
A preparation in the form of gelatin capsules is obtained by mixing the active ingredient with a diluent and by pouring the mixture obtained into soft or hard gelatine capsules. For the preparation of liquid compositions for oral administration, conventional inert diluents such as water or a vegetable oil may be used.
The liquid composition may contain, in addition to the inert diluent, auxiliaries such as moistening agents, suspension aids, sweeteners, aromatics, colorants, and preservatives. The liquid composition may be filled in capsules made of an absorbable material such as gelatine. Examples of solvents or suspension mediums used for the preparation of compositions for parenteral administration, e.g. injections, suppositories, include water, propylene glycol, polyethylene glycol, benzyl alcohol, ethyl oleate, lecithin and the like. Examples of base materials used for suppositories include, for example, cocoa butter, emulsified cacao butter, lauric lipid, witepsol.
According to proffered embodiment, this drug is used by the patients who have problem in the skeletal muscles. When this drug is taken by the patients which have problem or pain in their skeletal muscles it gives them much more relief.
The active ingredients are generally formulated in dosage units containing from 60 mg to 85 mg of zaltoprofen most preferably 80 mg and Img to 5 mg of thiocolchicoside most preferably 4 mg per unit dosage.

APPLICATIONS
- To control muscle spasm associated with acute, painful musculoskeletal conditions
- It is used for the treatment of muscular spasms and for rheumatologic, orthopedic, and traumatologic disorders
- Acute and chronic lumbar (low back) and sciatic pain
- Post-operative pain and spasm
- To relieve the stiffiiess, pain, and discomfort caused by strains, sprains, or other injury to muscles
- Spastic sequelae of hemiparests, Parkinson's disease

CLAIM,
We claim,
1) A muscle relaxant medicament comprises of active ingredients thiocolchicoside and zaltoprofen and other pharmaceutical excipients.
2) A muscle relaxant medicament, as in claim 1, wherein these compositions are preferably made so as to be administered by the oral, parenteral route, inject able (IV & IM ) ,local Spray, gel, aeroburn gel dressing or self adhesive bandage which comprises gel.
3) A muscle relaxant medicament, as in claim 1, wherein pharmaceutical compositions for compact administration such as granules, fine granules, powders, hard capsules, soft capsules, syrups, emulsions, suspensions, solutions and the like, or in the, form for sublingual a buccal administration.
4) A muscle relaxant medicament, as in claim 1, wherein Injections or drip infusions may be prepared as powdery preparations such as in the form of lyophilized preparations, and may be used by dissolving just before use in an appropriate aqueous medium such as physiological saline. Sustained-release preparations such as those coated with a polymer may be directly administered intracerebrally.
5) A muscle relaxant medicament, as in claim 1, wherein pharmaceutical compositions for parenteral administrations such as injections for intravenous, intramuscular, or subcutaneous administration, drip infusions, transdermal preparations, transmucosal preparations, nasal drops, inhalants, suppositories and the like Spray.
6) A muscle relaxant medicament, as in claim 1, wherein to provide a stable combination product providing superior analgesic, anti inflammatory and muscle relaxant property compared to plain thiocolchicoside tablets.
7) A muscle relaxant medicament, as in claim 1, wherein the active ingredients are generally formulated in dosage units containing from 60 mg to 85 mg of zeltoprofen most preferably 80 mg and Img to 5 mg of Thiocolchicoside most preferably 4 mg per unit dosage.

8) A muscle relaxant medicament, as in claim 1, wherein a medicament intended for treating musculoskeletal and joint disorders such as ankylosing spondylitis, low back pain, osteoarthritis, and rheumatoid arthritis, and peri-articular disorders such as bursitis and tendonitis, and painful muscle spasm such as Cervical Spondylitis, lumbago thereof.