A Synergistic Phytochemical Composition And A Process For Preparation Thereof

Abstract

The present invention provides a synergistic phytochemical composition from Curcuma longa possessing analgesic and anti inflammatory activity used for management of chronic pain and treatment of osteoarthritis  comprising:Curcuma longa oil from 0.5-5% by weight;Curcuma longa water extract from 95-99.5% by weight; and optionally pharmaceutically acceptable excipients.The present invention also provides a process for preparing the said composition.

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FIELD OF THE INVENTION
The present invention relates to a synergistic phytochemical composition useful for management of chronic pain and a process for preparing said composition.

BACKGROUND OF THE INVENTION
Physical disability and poor health often accompany knee osteoarthritis (OA  joint pains)  particularly as people age. This decline in function and quality of life is a complex phenomenon associated with numerous factors including pain  poor physical fitness  obesity  co-morbidity  low self-efficacy and lower extremity impairments. In addition to the functional losses associated with knee OA (joint pain) and aging  low levels of daily physical activity and exercise are common problems in this population for whom arthritis (joint pains) is a major reason for activity limitation.
Osteoarthritis is the most common type of arthritis  affecting 20 million people in America alone (Daniel O et al ; 2006)
Community survey data in rural and urban areas of India shows the prevalence of osteoarthritis to be in the range of 17 -60.6% (MK Sharma et al ; 2007)
Osteoarthritis (OA)  also known as degenerative arthritis or degenerative joint disease  is a clinical syndrome in which low-grade inflammation results in pain in the joints  caused by abnormal wearing of the cartilage that covers and acts as a cushion inside joints and destruction or decrease of synovial fluid that lubricates those joints. As the bone surfaces become less protected by cartilage  the patient experiences pain upon weight bearing  including walking and standing. Due to decreased movement because of the pain  regional muscles may atrophy  and ligaments may become more lax. OA is the most common form of arthritis. (Conaghan et al.  2008) and the leading cause of chronic disability in the United States. MMWR Morb Mortal  2008.
OA affects nearly 21 million people in the United States  accounting for 25% of visits to primary care physicians  and half of all NSAID (Non-Steroidal Anti-Inflammatory Drugs) prescriptions. It is estimated that 80% of the population will have radiographic evidence of OA by age 65  although only 60% of those will be symptomatic.(Green GA (2001). "Understanding NSAIDs: from aspirin to COX-2". Clin Cornerstone 3 (5): 50–60. PMID 11464731) In the United States  hospitalizations for osteoarthritis soared from about 322 000 in 1993 to 735 000 in 2006.(Hospitalizations for Osteoarthritis Rising Sharply Newswise  Retrieved on September 4  2008.)
Symptoms of OA: Joint pain  morning stiffness lasting less than 30 minutes  joint instability or buckling  loss of function
Signs of OA: Bony enlargement at affected joints  limitation of range of motion crepitus on motion  pain with motion  malalignment and/or joint deformity
Current management
Current treatment for OA is relatively limited. As there are currently no pharmacological agents capable of retarding or preventing the disease  treatment is predominantly focused on relief of pain  and maintenance of quality of life and functional independence.
Aside from weight reduction and avoiding activities that exert excessive stress on the joint cartilage  there is no specific treatment to halt cartilage degeneration or to repair damaged cartilage in osteoarthritis. The goal of treatment in osteoarthritis is to reduce joint pain and inflammation while improving and maintaining joint function.
The first line of drug treatment is with analgesics and non- steroidal anti-inflammatory drugs (NSAIDS). Only few of these NSAIDS are readily available as OTC from pharmacies without prescription as potential treatments for the pain and for other pain-syndromes. Standard references to the therapy of painful inflammatory disease attest to both the efficacy and adverse effects of these particular NSAIDs.
Pharmacological Therapy
1.Analgesic Agents
Several studies have shown acetaminophen to be superior to placebo and equivalent to non steroidal anti-inflammatory agents (NSAIDs) for the short-term management of OA pain. At present  acetaminophen (up to 4 000 mg/daily) is the recommended initial analgesic of choice for symptomatic OA. However  many patients eventually require NSAIDs or more potent analgesics to control pain. Oral glucosamine and chondroitin sulfate have been shown (each individually) to have a mild to moderate analgesic effect in several double-blind  placebo-controlled studies.
2. COX-2 Inhibitors
Cyclooxygenase-2 (COX-2) inhibitors are a class of non steriodal anti-inflammatory agents (NSAIDs) that received Food and Drug Administration (FDA) approval. These specific COX-2 inhibitors appear to be as effective as current non-selective NSAIDs in treating the pain and inflammation of arthritis. Their theoretical advantage  however  is that they will cause significantly less toxicity than conventional NSAIDs  particularly in the GI tract. Non steroidal anti-inflammatory drugs (NSAIDs) exert their anti-inflammatory effect primarily by inhibiting an enzyme called cyclooxygenase (COX)  also known as prostaglandin (PG) synthase. COX catalyzes the conversion of the substrate molecule  arachidonic acid  to prostanoids.
Prostanoids consist of prostaglandins E  D and F2 a  prostacyclin and thromboxane. The major inflammatory vasoactive prostanoids are PGE2 a and prostacyclin. Thromboxane is critical for platelet clotting  while PGD2 is involved in allergic reactions and PGF2 a in uterine contraction.
In addition to their inflammatory potential  prostaglandins also contribute to important homeostatic functions  such as maintenance of the gastric lining  renal blood flow  and platelet aggregation. Reduction of prostaglandin levels in these organs can result in the well-recognized side effects of traditional non-selective NSAIDs - that is  gastric ulceration  renal insufficiency  and prolonged bleeding time. The elderly are at higher risk for these side effects. For example  adults over the age of 60 who are taking NSAIDs have a 4-5 fold higher risk of gastrointestinal bleeding or ulceration then their age-matched counterparts. Other risk factors for NSAID-induced GI bleed include prior peptic ulcer disease and concomitant steroid use. Potential renal toxicities of NSAIDs include azotemia  proteinura  and renal failure requiring hospitalization. Hematologic and cognitive abnormalities have also been reported with several NSAIDs. Therefore  in elderly patients  and those with a documented history of NSAID-induced ulcers  traditional non-selective NSAIDs should be used with caution  usually in lower dose and in conjunction with a proton pump inhibitor. Renal function should be monitored in the elderly.
3. Local Analgesic Agents
Local analgesic therapies include topical capsaicin and methyl salicylate creams. Occasionally in late stage disease  patients will require narcotic analgesics to control pain.
4. Intra articular Therapies
Judicious use of intra-articular glucocorticoid injections is appropriate for OA patients who cannot tolerate  or whose pain is not well controlled by  oral analgesic and anti-inflammatory agents. Periarticular injections may effectively treat bursitis or tendonitis that can accompany OA. The need for four or more intra-articular injections suggests the need for orthopedic intervention.
Intraarticular injection of hyaluronate preparations has been demonstrated in several small clinical trials to reduce pain in OA of the knee. These injections are given in a series of 3 or 5 weekly injections (depending on the specific preparation) and may reduce pain for up to 6 months in some patients.
Non-pharmacological Management includes Weight reduction  Exercise /resistive strengthening
Side effects of current therapies
Analgesics: These agents are not recommended for prolonged use because they cause constipation and increase the risk of falling  particularly in the elderly.
NSAID: The most common side effects are dyspepsia  diarrhea  abdominal pain  gastric ulceration  renal insufficiency  and prolonged bleeding time
Prior Art
Curcuma longa Linn.  commonly known as turmeric is a plant that belongs to the family Zingiberaceae. Its rhizome is widely used in indigenous medicine and as part of household remedies. It is also applied in poultices to relieve pain and inflammation
The rhizomes contain curcumin (C21H20O6)  a yellow colored phenolic pigment which is considered as the main active constituent. In purified extracts of C. longa about 70 to 76 % of curcumin is present  along with about 16% demethoxycurcumin and 8% bisdemethoxycurcumin. Studies have demonstrated a wide spectrum of therapeutic effects  such as anti-inflammatory  antioxidant  antitumor  antibacterial  antifungal  antiviral  anti-spasmodic  immunomodulatory and hepatoprotective activities for this plant and curcuminoids. Recently its potential utility in acquired immune deficiency syndrome (AIDS) has been demonstrated. The rhizomes also contain oil comprising of a set of constituents known as turmerones which have also been shown to possess anti-inflammatory activity. Preclinical (in vivo and in vitro)  toxicological and clinical studies have been carried out and the plant is found to be safe and effective. (Akram  et al.  2010  Julie  et al.  2009 and Rebecca  2011)
Some of the polysaccharides isolated from the plant have shown modulatory effects on release of cytokines in peripheral blood mononuclear cells (PBMC) and on reticulo endothelial systems. (Yue  et al.  2010  Gonda  et al.  1993  Gonda  et al.  1992 a  Gonda  et al.  1992 b and Gonda  et al.  1990)
The currently available herbal products which are meant for relieving pain are not very effective. Other available options in medical treatments aim at reducing the pain in patients with osteoarthritis including analgesics and anti-inflammatory drugs used in current therapeutic regimes have suboptimal reduction in pain and are associated with variety of side effects. There is therefore a need for new herbal products which are safe and highly effective against osteoarthritic pain.

SUMMARY OF THE INVENTION
In order to alleviate the drawbacks of the various methods for treating osteoarthritis available in the prior art  the applicant has developed a novel synergistic phytochemical composition from Curcuma longa comprising aqueous water extract of Curcuma longa and Curcuma longa oil for treating osteoarthritis. Such fractions devoid of curcuminoids are shown to possess anti-inflammatory activity in in vitro assay models and synergistic effect is exhibited when they are blended in specific proportions.

The present invention also provides a process for preparation of the synergistic phytochemical composition of the invention.

The present invention further provides functional foods comprising the phytochemical composition.

DETAILED DESCRIPTION OF THE INVENTION
The present invention provides a synergistic phytochemical composition possessing analgesic and anti inflammatory activity  comprising:
Curcuma longa oil from 0.5-5% by weight;
Curcuma longa water extract from 95-99.5 % by weight; and optionally
pharmaceutically acceptable excipients.

The composition of the invention preferably comprises:
Curcuma longa oil 1% by weight;
Curcuma longa water extract 99% by weight; and optionally pharmaceutically acceptable excipients.

The pharmaceutically acceptable excipients of the composition are selected from a group comprising granulating agents like binding agents ( Eg : Poly vinyl pyrrolidone (PVP) and Starch )  lubricating agents ( Eg : Magnesium stearate and talc)  disintegrating agents ( Eg : Cross carmellellose sodium and Crospovidone)  sweetening agents ( Eg : Mannitol and sucrose )  coloring agents ( Eg : Sunset yellow and Tartruzine )  flavoring agents ( Eg : Wild cherry  Vannila and Mint )  coating agents ( Eg : shellac and Hydroxy propyl paraben )  plasticizers ( Eg : Glycerin  Sorbitol and Mineral oil )  preservatives ( Eg : Methyl patraben and Propyl paraben )  suspending agents ( Eg : Carboxy methyl cellolose sodium and Guar gum )  emulsifying agents ( Eg : Acacia and Methyl cellulose ) and spheronization agents ( Eg : Micro crystalline cellulose and Carboxy methyl cellulose sodium).

The composition of the present invention may be formulated into a wide range of dosage forms selected from the group comprising tablets  troches  lozenges  aqueous or oily suspensions  dispersible powders or granules  emulsion in hard or soft gel capsules  syrups  elixirs  phytoceuticals  neutraceuticals and food stuffs by mixing with GRAS (Generally Regarded As Safe) grade of pharmaceutical excipients to prepare various dosage forms like capsules  tablets  syrups  lozenges etc. The excipients which can be used may be selected from starch  di-calcium phosphate  polysorbate  fumed silica  etc. The food stuffs in which the synergistic herbal composition may be used as a dietary supplement / food additive is selected from the group comprising bread  pizza  health drinks  biscuits  chocolates  pasta etc.

The present invention also provides a process for preparing the phytochemical composition  comprising:
a. extracting the curcuminoids from the rhizome of Curcuma longa;
b. recovering the solvents from the raw material bed;
c. extracting the rhizomes of Curcuma longa left after steps a and b using water by maceration at room temperature and followed by refluxing at 80-100°C;
d. concentrating the water extract by distillation under vacuum at less than 80°C to achieve total solid content of 15-35% w/v;
e. spray drying the concentrated liquid extract to get powdered aqueous extract;
f. precipitating the curcuminoids from the oleoresin obtained from step a using suitable solvents and obtaining curcumin removed turmeric oleoresin;
g. distilling the curcumin removed turmeric oleoresin using steam or by high vacuum distillation to get oil of Curcuma longa;
h. mixing the aqueous extract (obtained from point e) and the oil (obtained from point g) in the specified proportion to yield the synergistic composition derived from Curcuma longa.

Extraction of curcuminoids from the rhizome of Curcuma longa is carried out using the established procedures known in the industry which includes solvent extractions using acetone  dichloroethane  dichloromethane  methanol  ethylacetate  methyl ethyl ketone  toluene or mixtures of these solvents.
The step of recovering solvents from the raw material bed is carried out using standard techniques like steam stripping. Further  solvents used for precipitating curcuminoids from oleoresin are selected from the group comprising isopropyl alcohol and methanol.

Additionally  the present invention also provides use of the phytochemical composition in inhibiting PGE2  IL-12  and stimulation of IL-10 activity which results in anti inflammatory effect and in prevention and treatment of osteoarthritis.

The present invention further provides a method for preventing and treating osteoarthritis in a subject comprising administering pharmaceutically effective amount (0.5 - 2gm/day) of the composition along with pharmaceutically acceptable additives. The composition may be administered in any dosage form like capsules  tablets  syrups  lozenges  etc.

The composition of the present invention is safe and non-toxic with no side effects.

The present invention is explained further in the following specific examples which are only by way of illustration and are not to be construed as limiting the scope of the invention.

EXAMPLES
Example 1: Preparation of the Composition

100g of powdered Curcuma longa rhizomes is taken and refluxed with 400ml of acetone for 2 hours. The liquid extract is filtered and marc extracted two more times with acetone in the same manner. The acetone soluble part (combined three washes) is concentrated by distillation under vacuum at less than 50 degree centigrade and the curcuminoids removed from the extract by precipitation and crystallization with isopropyl alcohol to yield curcumin removed oleoresin. Curcumin removed oleoresin is distilled by passing steam and the steam distillate and separate oil layer are collected.

The acetone insoluble part of rhizomes  which is almost free from curcuminoids  is refluxed with 400ml of water at 90-95 degree centigrade for 3 hours. The liquid water extract is collected by filtration and the marc extracted two more times with water in the same manner. The liquid water extract (combined from three washes) is concentrated by distillation under vacuum at less than 75 degree centigrade to have about 20 to 35% total solids. The concentrated liquid extract is spray dried to get a powdered water extract. The powdered water extract is mixed with the oil in 99:1 proportion in a blender and sieved through 60 mesh to get the final composition.

Example 2: Data on Synergy of present composition
Relevance of Lymphocyte Proliferation assay: The lymphocyte proliferation assay (LPA) is used to identify the possible immunostimulatory or immunosuppressant effects of various natural products (drugs) on isolated whole murine splenocytes (Namgoong  et al.  1994  Lee  et al.  1995  and Koch  et al.  2001). Overall  the body""s immune response has one primary function: to protect the body from an object that the body does not recognize as a normal object. The immune response can be either normal or abnormal. Inflammation is also one of the body""s first responses to infections as the body tries to rush immune cells and cytotoxic chemicals to the infected tissue to defend against the infections or foreign particles.
Arthritis tends to develop inflammation in the joints and their surrounding tissues.
Summary of the study: Successive water extract of C. longa and the composition of the invention showed significant increase at the tested concentrations. The EC50 value of successive water extract of C. longa and the composition of the invention were found to be ~ 7 µg/mL and ~ 4 µg/mL respectively. C. longa oil showed increase in splenocyte number at a concentration of 0.8 µg/mL to 1.6 µg/mL followed by decrease in subsequent concentrations. The composition of the invention showed 2 times more potent activity compared to successive water extract of C. longa whereas C. longa oil did not show appropriate activity at the tested concentrations. This explains the synergistic activity of the composition of the invention. From the above study  the immunomodulatory potential of the successive water extract of C. longa  C. longa oil and the composition of the invention are in the following order: PC/PT/1004006BP > PC/PT/1004006B > PC/0805.

Example 3: Effect of water extract of C. longa  C. longa oil and the composition of the invention on IL-12 levels in LPS induced murine splenocytes.
Relevance of Interleukin-12 assay: IL-12 is an important mediator of inflammatory diseases such as psoriasis  multiple sclerosis  rheumatoid arthritis and Crohn’s diseases. IL-12 plays a role in inflammatory cell recruitment via PMN production of IL-8  the most potent chemokine for PMNs themselves. IL-12  produced early during the response to infectious agents  could thus promote rapid IL-8-induced PMN influx (Ethuin et al.  2001). Recent attention has turned towards IL-12 family of cytokines as a promising area of study for inflammation associated diseases and inhibition of this cytokine synthesis may have therapeutic applications (Katrina  et al.  2009).
Summary of the Study: In this study  the effect of water extract of C. longa  C. longa oil and the composition of the invention was evaluated on the release of IL-12 levels in LPS treated murine splenocytes. Water extract of C. longa  C. longa oil and the composition of the invention showed significant dose dependent inhibition of LPS induced IL-12 levels in murine splenocytes. The EC50 values of water extract of C. longa  C. longa oil and the composition of the invention was found to be 3µg/mL  13µg/mL and 2µg/mL respectively. From the above results  it can be concluded that inhibition of LPS induced IL-12 release of the composition of the invention is mainly attributed to water extract of C. longa.

Example 4 : Effect of the composition of the invention on IL-10 levels in naive murine splenocytes
Relevance of assay: IL-10 is a potent and broad-spectrum anti-inflammatory cytokine  secreted by diverge category of cells. It is capable of inhibiting the synthesis of pro-inflammatory cytokines like IFN-gamma  IL-2  IL-3  TNF-alpha and GM-CSF by blocking NF-kappa B activity (Siebenlist et al.  1994).
Summary of experiment: The effect of the composition of the invention was evaluated on the release of IL-10 levels in murine splenocytes. Composition of the invention exhibited significant dose dependent increase in IL-10. The EC50 value of composition of the invention was found to be ~ 52 µg/mL. From the above results  it can be concluded that composition of the invention has antiinflammatory activity by inducing IL-10 release from murine splenocytes

Example 5: Effect of the composition of the invention on LPS induced PGE2 level in mouse splenocytes
Relevance of PGE2 assay : The cyclooxygenase (COX) pathway is a major route for metabolism of arachidonic acid (AA)  which is converted to cyclic prostaglandins (PGG and PGH) and subsequent metabolic products such as PGE2 and PGD2 (Halliwell  et al.  2004) . It has been postulated that PGE2 is a necessary intermediate in the acute inflammatory response and thus can serve as an excellent target for inflammatory conditions like osteoarthritis (Molloy and McCarthy  2005; Fahmi 2004) and inflammation associated disorders (Williams  et al.  1999; Hata and Breyer  2004; Yedgar  et al.  2006).
Summary of experiment: The effect of the composition of the invention was studied in LPS induced PGE2 release in murine splenocytes. The composition of the invention showed significant dose dependent inhibition of LPS induced PGE2 levels in murine macrophage cells. The EC50 value of the composition of the invention was found to be 174 µg/mL. In conclusion  composition of invention showed anti-inflammatory activity by reducing LPS induced PGE2 levels.

Example 6: Effect of the composition of the invention on IL-12 levels in LPS induced murine splenocytes.
Relevance of Interleukin-12 assay: IL-12 is an important mediator of inflammatory diseases such as psoriasis  multiple sclerosis  rheumatoid arthritis and Crohn’s diseases. IL-12 plays a role in inflammatory cell recruitment via PMN production of IL-8  the most potent chemokine for PMNs themselves. IL-12  produced early during the response to infectious agents  could thus promote rapid IL-8-induced PMN influx (Ethuin et al.  2001). Recent attention has turned towards IL-12 family of cytokines as a promising area of study for inflammation associated diseases and inhibition of this cytokine synthesis may have therapeutic applications (Katrina  et al.  2009).
Summary of the Study: In this study  the effect of the composition of the invention was evaluated on the release of IL-12 levels in LPS treated murine splenocytes. The composition of the invention showed significant dose dependent inhibition of LPS induced IL-12 levels in murine splenocytes. The EC50 value of the composition of the invention was found to be 2µg/mL. From the above result  it can be seen that inhibition of LPS induced IL-12 release of the composition of the invention is mainly attributed to its antiinflammatory property.
Based on Examples 3  4 and 5  it can be seen that the mechanism of anti-inflammatory activity of the composition of the invention is due to
1. Stimulation of IL-10 release
2. Inhibition of PGE2 release
3. Inhibition of IL-12 release

Example 7: Evaluation of anti-inflammatory activity of the composition of the in xylene induced ear edema model using albino Swiss mice
Summary of Xylene induced ear edema model using albino Swiss mice: The objective of this study is to evaluate the anti-inflammatory activity of the composition of the invention in xylene induced ear edema model  when administered as a single oral dose to male albino Swiss mice. The composition of the invention at all the tested doses (90  180 and 360 mg/kg) showed significant anti-inflammatory activity as compared to vehicle control group. Based on the findings of this study  it can be stated that the composition of the invention revealed significant anti-inflammatory activity at all the tested dose levels  with optimal activity observed at 90 mg/kg in xylene induced ear edema model in Swiss albino mice.

Example 8: Evaluation of anti-inflammatory activity of the composition of the invention in cotton pellet granuloma model using albino Wistar rats
Cotton pellet granuloma model using albino Wistar rats: The present study was undertaken to evaluate the anti-inflammatory activity of the composition of the invention in cotton pellet granuloma model using albino Wistar rats. The composition of the invention at doses of 45  90 and 180 mg/kg significantly reduced both wet and dry weights of the cotton pellets as compared to vehicle control group. Based on the results of the present study  it can be stated that the composition of the invention revealed significant anti-inflammatory activity at all the tested doses  with optimal anti-inflammatory activity observed at 45 mg/kg in cotton pellet granuloma model using albino Wistar rats.

Example 9: Acute Oral Toxicity Study of the composition of the invention in Albino Wistar Rats
Acute oral toxicity study of the composition of the invention was conducted in female albino Wistar rats. Administration of the composition of the invention at the higher dose level of 5000 mg/kg  b.w. showed neither mortality nor abnormal clinical signs. Overall weight gain of treated animals was found to be normal during the study duration. On necropsy  no major gross pathological changes were observed in any of the treated rats. From these results  it is concluded that the composition of the invention was found to be safe as a single dose oral administration to female albino Wistar rats up to 5000 mg/kg  b.w.

Example 10 : Salmonella reverse mutation assay for the composition of the invention
Salmonella reverse mutation assay: Salmonella reverse mutation assay was conducted to test the mutagenic potential of the composition of the invention using S. typhimurium tester strains viz.  TA98 and TAMix. The composition of the invention was tested at the concentrations of 5000 µg/ml  1510 µg/ml and 450 µg/ml  140 µg/ml  40 µg/ml and 10 µg/ml using phosphate buffered saline (PBS) as solvent and with and without the metabolic activation (S9 fraction).
The composition of the invention did not induce mutation both in the presence and absence of metabolic activation in S. typhimurium mutant strains TA98 and TAMix at all the concentrations tested. This study suggests that the composition of the invention is non-mutagenic up to a concentration of 5000 µg /ml.

Example 11: Clinical Studies
Safety and efficacy of the composition of the invention in the treatment of painful osteoarthritis: a randomized  single blind  placebo-controlled trial
The present trial was carried out to evaluate the effectiveness of the composition of the invention in the treatment of painful OA [a randomized  single blind  placebo-controlled trial]. 120 patients (37 males and 83 females) with primary OA received either the composition of the invention (500 mg twice daily) or Glucosamine sulphate (750mg twice daily) or placebo (500mg twice daily) or combination of the composition of the invention and Glucosamine sulphate for 42 days. During the treatment period two follow up visits on day 21st and day 42nd   efficacy was evaluated in terms of change in the intensity/severity of symptoms (as measured by VAS  WOMAC scale) and examination by orthopaedician (as measured by CGIC). The analysis of scores of all symptoms (over the period) in the composition of the invention treated group after 21st and 42nd days of treatment  were found to be significantly decreased when compared to placebo group (WOMAC - p<0.05; VAS - p<0.05; CGIC - p<0.001). Similarly  the composition of the invention treated group showed remarkable decrease in the use of rescue medication (p<0.05) along with clinical and subjective improvement in comparison to the placebo group.

Overall improvement in signs and symptoms of OA were seen with Glucosamine sulphate and its combination with the composition of the invention  but this was not statistically significant. Treatment with the composition of the invention was found to be safe and well tolerated by all patients during the intervention period.

The above findings demonstrate the efficacy of the composition of the invention and that it could possibly be a safer and effective option for the treatment of patients with primary painful knee OA.

I CLAIM:

1. A phytochemical composition comprising:
(a) 0.5-5% by weight Curcuma longa oil;
(b) 95-99.5% by weight Curcuma longa water extract; and optionally
(c) pharmaceutical excipients.
2. The phytochemical composition as claimed in claim 1  preferably comprising:
(a) 1% by weight Curcuma longa oil;
(b) 99% by weight Curcuma longa water extract; and optionally
(c) pharmaceutically acceptable excipients.
3. The phytochemical composition as claimed in claim 1  wherein the pharmaceutically acceptable excipients are selected from the group comprising granulating agents  binding agents  lubricating agents  disintegrating agents  sweetening agents  colouring agents  flavouring agents  coating agents  plasticizers  preservatives  suspending agents  emulsifying agents and spheronization agents.
4. The phytochemical composition as claimed in claim 1  wherein the composition may be formulated into a dosage form selected from the group comprising capsules  tablets  syrups  lozenges  troches  elixirs  phytoceuticals and neutraceuticals by mixing with pharmaceutically acceptable excipients.
5. The phytochemical composition as claimed in claim 4  wherein the pharmaceutically acceptable excipients are selected from the group comprising starch  di-calcium phosphate  polysorbate and fumed silica.
6. A process for preparing the phytochemical composition as claimed in claim 1  comprising:
a. extracting curcuminoids from the rhizome of Curcuma longa;
b. recovering solvents from the raw material bed;
c. extracting the rhizomes of Curcuma longa left after steps a and b using water by maceration at room temperature and followed by refluxing at 80-100°C;
d. concentrating the water extract by distillation under vacuum at less than 80°C to achieve total solid content of 15-35% w/v;
e. spray drying the concentrated liquid extract to get powdered aqueous extract;
f. precipitating the curcuminoids from the oleoresin obtained from step a using suitable solvents and obtaining curcumin removed turmeric oleoresin;
g. distilling the curcumin removed turmeric oleoresin using steam or by high vacuum distillation to get oil of Curcuma longa;
h. mixing the aqueous extract (obtained from point e) and the oil (obtained from point g) in the proportion as claimed in claim 1 to yield the phtochemical composition derived from Curcuma longa.
7. The process as claimed in claim 6  wherein the step of extracting curcuminoids from rhizome is done by extraction using solvents selected from the group comprising acetone  dichloroethane  dichloromethane  methanol  ethylacetate  methyl ethyl ketone  toluene or mixtures of these solvents.
8. The process as claimed in claim 6  wherein the step of recovering solvents from raw material bed is done by steam stripping.
9. The process as claimed in claim 6  wherein curcuminoids are precipitated from oleoresin using solvents selected from the group comprising isopropyl alcohol and methanol.
10. A food product comprising the pharmaceutical composition as claimed in claim 1.
11. The food product as claimed in claim 8  selected from the group comprising bread  pizza  health drinks  biscuits  chocolates and pasta.
12. The phytochemical composition as claimed in claim 1  useful for the relief of chronic pain and treatment of osteo arthritis.

Dated this 25th day of August 2011
Signature


SANTOSH VIKRAM SINGH
Patent Agent
Agent for the Applicant

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