FORM 2
The Patents Act, 1970
(39 of 1970)
COMPLETE SPECIFICATION
[See,section 10]
"Natural Composition for Arthritis"
APPLICANT
Ajanta Pharma Limited
An Indian Company,
Registered under Companies Act, 1956
and having its Registered Office at:
Ajanta House, 98 Govt. Industrial Area,
Charkop, Kandivli (W), Mumbai - 400 067,
Maharashtra, India
INVENTOR
The inventors under Sec.28 are: i) BIYANI, Milind Kesharlal ; ii) BANAVALIKAR Manisha Manohar; iii) CHOTALIA Chetna Sanjay;
Working as Research Scientists at Research Centre,
Ajanta Pharma Limited,
Ajanta House, Charkop, Kandivli (W),
Mumbai - 400 067, Maharashtra, India
Nationality: All being Indian citizens.
The following specification particularly describes the nature of the invention and the manner in which it is to be performed.



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FIELD OF THE INVENTION:

The present invention relates to the natural composition

for arthritis comprising of herbal constituents for
synergistic effect. More particularly it relates to the

composition prepared preferably from the extract of the herbs.
The present invention composition is indicated in osteoarthritis, rheumatic pain, and joint Plains, especially to improve mobility.
BACKGROUND OF THE INVENTION:
Arthritis is a progressive disease of various etiologies. Common symptoms are pain and inflammation of one or more joints. The chronic clinical diagnostic includes non-specific usually symmetric inflammation of the peripheral joints, with pain, tenderness, and swelling of affected joints; leading to slow progressive joint destruction and deformity. Morning stiffness is common; frequently involving PIP and MCP joints. Consistent inflammation damages tissue causing loss of cartilage, erosion of bone matter and subluxation of the joint resulting into a high degree of morbidity causing disturbance in normal routine life of the patient. However one of the most the prevalent problem is immobility associated with arthritis, when arthritic joints make even slightest movement painful, it slows down the patient considerably or even leaves patient immobile.
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For the management of pain and inflammation first line

treatment includes drugs classified as nonsteroidal anti-inflammatory drugs (NSAIDS} e.g. aspirin, ibuprofen etc.

Secondary treatment include corticosteroids, slow acting antirheumatic drugs (SAARDS) or disease modifying drugs (DMs), e.g., penicilliinamine, cyclophosphamide, gold salts, azothiprine, levamisole, etc. However most of them are cytotoxic and there are sever side effects associated with these drugs such as gastric erosion and adverse effects on kidneys and liver. Moreover they have low benefit-risk ratio since their effects are mainly of- short duration, and their use disadvantageous over an extended periods of time owing to their adverse side effects.
Therefore there is need for a natural composition which improves mobility, reduces pain and helps in management of arthritis, at the same time safe and can be used as long as required,
PRIOR ART:
U.S. patent no. 5494668 (February 27, 1996} describes a method of treating degenerative musculoskeletal diseases such as ' rheumatoid arthritis and osteoarthritis in an animal, typically a human, by enteric administration of a therapeutically effective amount of the beneficial extracts of the plants Withania somnifera, Boswellia serrata, Curcuma longa and Zingiber officinale in a predetermined proportion to each other.
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U.S. Patent no. 5683698 (November 4, 1997) describes a herbal formulation and its use for reducing/alleviating symptoms associated with rheumatoid arthritis, osteoarthritis and reactive arthritis and for reducing the production of proinflammatory cytokines. The formulation comprises of Alpinia galanga, Smilax glabra, Tinospora cordifolia, Tribulus terrestris, Withania somnifera and Zingiber officinale.
U.S. patent no. 5707631 is directed to a therapeutic herbal composition including Trigonella foenum-graecum seed, Syzygium aromaticum fruit, Allium sativum bulb, Cinnamomum zeylanicum bark, Saussurea costus root and Euphorbia lathyris bud together with sodium chloride (preferably sea salt).
• U.S. patent no. 6274176 (August 14, 2001} describes an edible composition for use as an anti-inflammatory agent for alleviation of arthritis and gout in mammals. The edible composition is a mixture of at least three, preferably at least seven herbs selected from the group consisting of Tanacetum parthenium, Zingiber officinale, Curcuma longa, Coriandrum sativum, Centella asiatica, Oenothera biennis, Valeriana officinalis, Tabebula impetiginosa, Thymus vulgaris, and Sambucus nigra. The composition preferably contains the herbs in approximately equal amounts.
International patent application no. WO02025832 (January 24, 2002) provides compositions containing herbal
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extracts from Achyranthus roots and Atractylodes japonica roots for preventing and treating arthritis and a manufacturing method of the same.
Thus it is quite evidenl form the above that there are plenty of priors art with reference to herbal medicines for arthritis. Although the use of various herbs are previously described the present invention natural composition comprising of herbal constituents for synergistic effect preferably the extract of the herb which is intended to be used for not only osteoarthritis, rheumatic pain, or joint pains, but especially for improving mobility and thereby contributing to effective management of arthritis has never been described before.
OBJECTS OF THE INVENTION:
The object of the present invention is to provide the natural composition for arthritis comprising of herbal constituents preferably in the extract form for synergistic effect.
It is therefore the object of the invention to provide the natural composition comprising of synergistic herbal constituent selected from Cornrniphora mukul (Guggulu) , Cedrus deodara (Devdaru), Boerhaavia diffusa (Punarnava), Zingiber officinaie (Sunthi), Pluchea lanceolata (Rasna), Withania somniferfe (Ashwagandha); Ricinus communis (Erand mula) or the like.
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It is another object of the invention to provide the natural composition, which can be used, thereto for osteoarthritis, rheumatic pain, and joint pains, especially to improve mobility, at the same time safe and can be used as long as required.
It is further object of the invention to provide the composition in suitable oxal dosage forms like tablets, capsules, granules, powders, effervescent preparations, teas or the like.
It is still another object of the invention to provide the natural composition formulated so as to have better shelf life and stability.
It is also an object of the present invention to provide the process for preparation of natural composition for
arthritis comprising of herbal constituents preferably in the
extract form for synergistic" effect.
It is also an object of the present invention to provide the process for preparation of natural composition comprising of synergistic herbal constituent selected from Commiphora mukul (Guggulu) , Cedrus deodara (Devdaru) , Boerhaavia diffusa (Punarnava), Zingiber officinale (Sunthi), Pluchea lanceolata (Rasna), Withania somnifera (Ashwagandha); Ricinus communis (Erand mula) or the like.
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It is also an object of the present invention to provide the process for preparation of the natural composition, which can 'be used, thereto for osteoarthritis, rheumatic pain, and joint pains, especially to improve mobility, at the same time safe and can be used as long as required.
It is also an object of the present invention to provide the process for preparation of the composition in suitable oral dosage forms like tablets, capsules, granules, powders, effervescent preparations, teas or the like.
It is also an object of the present invention to provide the process for preparation of the composition with better, shelf life and stability.
DETAILED DESCRIPTION:
The present invention provides preparation of natural composition for arthritis comprising of herbal constituents preferably in the extract form for synergistic effect, used thereto for osteoarthritis, rheumatic pain, joint pains, especially for improving mobility, which is safe, and can be used as long as required.
The present invention composition for arthritis for synergistic effect comprise of herbal constituents like Commiphora mukul (Guggulu) , Cedrus deodara (Devdaru), Boerhaavia diffusa (Punarnava) , Zingiber officinale (Sunthi),
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Pluchea lanceolata (Rasna), Withania somnifera (Ashwagandha);

Ricinus communis (Erand mula) or the like.
Commiphora mukul kwon in Ayurveda as Guggulu is a time tested anti-inflammatory, analgesic, anti-rheumatic agent. It. acts as a demulcent by providing lubrication to the joints and facilitating their movements.
Cedrus deodara known traditionally as Devdaru is an anti-inflammatory agent in arthritis. The anti-inflammatory activity is attributed to its mast cell stabilizing activity and inhibition of leukotriene synthesis.
Boerhaavia diffusa commonly known as Punarnava has anti-inflammatory activity similar to hydrocortisone. It inhibits the increased serum aminotransferase activity in arthritic conditions similar to hydrocortisone. It also, relieves muscular pain.
Zingiber officinale known as Sunthi is an anti-inflammatory agent. It has been shown to inhibit the activities of cyclo-oxygenase and lipoxygenase in the arachidonic acid cascade. Thus, its anti-inflammatory actions may be due to a decrease in the formation of prostaglandins and leukotrienes.
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Pluchea lanceolata in Ayurveda known as Rasna shows
significant anti-inflammatory activity.it also has analgesic and anti-pyretic actions.
Withania somnifera in Sanskrit called as . Ashwagandha inhibits immunologically induced inflammation due to the plant steroid present withaferin A. Withanolides are also said- to possess anti-inflammatory activity. It also has free radical - scavenging activity, which is important since arthritis is also associated with free radical damage of cartilage and other joint tissues. The anti-anxiety and tranquilizing actions of Ashwagandha are added advantages in stress, which are usually present in patients of arthritis.
Ricinus communis roots traditionally called as Eranda mula has anti-inflammatory properties. It helps' in reducing inflammation of joints and early-morning stiffness.
In accordance with the present invention it is the synergistic effect of all the afore-mentioned herbal constituents provided in a single dosage unit, which eventually provides the holistic effect of the composition. It would not be possible to obtain the desired effect by administration of individual components of the composition separately. It is believed that when incorporated together the herbal constitutes provides the effect grater than the sum of the effect of each of the constituents. Each of the herbal constituents is incorporated to potentiate the effect
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of each other without giving any toxic or harmful side
effect.
The present invention composition comprises of the herbal constituents in the extract form in an amount ranging from Commiphora mukul 25 mg to 500 mg, Cedrus deodara 50 mg to 500 mg, Boerhaavia diffusa 50 mg to 500 mg, Zingiber officinale 25 mg to 250 mg, Pluchea lanceolata 25 mg to 250 mg, Withania somnifera 50 mg to 500 mg, Ricinus communis 10 mg to 250 mg.
The present invention composition further comprises of the pharmaceutically acceptable safe inert adjuvants for formulating the composition into suitable oral dosage forms. In accordance with the present invention, the composition comprises of pharmaceutically acceptable safe inert adjuvants selected from but not limited to diluents like lactose, sucrose, cellulose, microcrystalline cellulose, tribasic calcium phosphate, maltodextrin, or the like; disintegrating agents like starch, sodium starch glycolate, crospovidone, croscarmellose sodium; lubricants like magnesium stearate, calcium stearate, talc, or the like; glidants like colloidal silicone dioxide or the like; coating agents like" eudragit, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose; and or other adjuvants known in the field of the art. The present invention composition comprises of the pharmaceutically inert adjuvants in an
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amount ranging from 0.1 % to 50 % weight by weight per unit
dosage form.
The present invention composition is formulated in the suitable oral dosage form such as tablets, capsules, syrups, suspensions, granules, powders, effervescent preparations, teas or the like.
The present invention composition was prepared by direct compression method without invloving granulation. It was observed that direct compression method helped in improving the stability of the composition. As the process does not involve the wet granulation step, subjecting of the sensitive herbal active ingredients to higher temperature was avoided. To further improve the stability core tablets were coated by transparent coating. This in addition to improving the stability, it also enhanced the other physical properties of the tablet like hardness and friability.
The present invention composition was formulated in accordance with process described herein. The process comprises of: mixing all the active herbal ingredients and sifting through 20 mesh British "standard sieve; mixing of herbal constituents with pharmaceutical adjuvants like diluents, disintegrant, glidant or the like, already passed through 40 mesh British standard sieve, mixing was continued for 10 minutes; blending of active ingredient and excipients; lubricating the blend with lubricating agent; compressing the
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blend into tablets using suitable dies and punches; coating of the core tablets using cellulosic or other suitable polymeric material. Alternatively blend prior to lubrication can be filled into capsules or sachets or the like.
The following examples illustrate but do not limit the scope of the invention. It should be understood that various changes and modifications would be apparent to those skilled in the art. However such changes and modifications of the present invention can be made without departing from its spirit and scope and without diminishing its attendant advantages.
EXAMPLES
Example 1
The present invention composition was formulated into tablet by following process:
Commiphora rnukul extract 200 mg, Cedrus deodara extract 200 mg, Boerhaavia diffusa extract 150 mg, Zingiber officinale extract 150 mg, Pluchea lanceolata extract 100 mg, Withania somnifera extract 100 mg, Ricinus communis extract 50 mg were mixed and passed through 20 mesh BSS sieve, blend of active herbal constituents was mixed with microcrystalline cellulose (190 mg) , colloidal silicone dioxide (10 mg), croscarmellose sodium (15 mg) , talc (7 mg) previously passed through 40 mesh BSS sieve, The active and excipient blend was
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lubricated with magnesium stearate (5 mg), lubricated blend was compressed into tablets using 13 mm standard . concave punches. The core tablets were film coated using low viscosity hydroxypropylmethyl cellulose polymer.
Example 2:
A comparative double blind, non crossover placebo controlled clinical trial was carried out using 1 tablet of example 1 thrice daily for test group and 1 placebo tablet thrice daily for control group for judging the clinical efficacy of the present invention. Patients suffering from symptoms of osteoarthritis were enrolled. Total 18 patients completed the trial. .Efficacy was evaluated on the basis on symptomatic improvement, reduction in affected joint size, improvement in walking time and x-ray findings.
It was observed that the present invention composition was effective in alleviating symptoms of joint pain, stiffness, and tenderness, swelling, squatting difficulties and -inability to walk long distance. The percentage reduction observed in the symptoms in drug and placebo group were the follows

Symptoms Drug Placebo
Joint Pain 65.07% 17.78%
Stiffness 65.39% 16.67%
Tenderness 69.27% 25%
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Swelling 75% 25%
Squatting Difficulties 61.73% 16.64%
Inability To Walk 65.12% 14.45%
There was also observed the improvement in walking time and reduction in affected joint size. Percentage increase in the walking time and percentage reduction in the joint size were as follows;

Parameter Drug Placebo
Walking time 96% 9.5%
Joint Size 25.29% 5.69%
X - Ray Findings were as follows in drug group patients,
1. Soft tissue swelling was reduced in all the 9 patients.
2. Erosion decreased in 6 patients.
3. Osteophyte changes were observed in 3 patients.
No changes were observed in x - ray findings in all the 9 patients of placebo group.
Safety: Results of safety study indicated the following,-liver function and kidney function tests were carried out before and after treatment. No significant changes were observed in these parameters indicating the safety of the product.
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Therefore the above study suggests that the present invention natural composition by way of synergistic effect of all the constituents relieved the symptoms associated with arthritis and helped in improvement of mobility which is evident from improvement in the parameter like 96% increase in walking time in drug group as against only 9.5% increase in walking time in placebo group. Moreover no adverse events were observed during -the study of liver function and kidney function and they remained normal after the administration of the present invention composition hence proving its safety.
Thus the above finding substantiates the usefulness of the present invention natural composition in management of osteparthritis, rheumatic pain, and joint Pains, especially in improvement of mobility and also its safeness in use for the prolonged period.
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We Claim:
1. The natural composition for arthritis comprising of
herbal constituents for synerqistic effect like Commiphora
mukul 25 mg to 500 mg, Cedrus deodar a 50 mg to 500 mg,
Boerhaavia diffusa 50 mg to 500 mg, Zinglber officinale 25 mg. to 250 mg, Pluchea lanceolata 25 mg to 250 mg, Withania
somnifera 50 mg to 500 mg, Ricinus communis 10 mg to 250 mg
«
or the like and pharmaceutically acceptable safe inert adjuvants in oral dosage form with better shelf life and stability, useful in osteoarthritis, rheumatic pain, and joint Pains, especially for improving mobility in the persons in the need thereof.
2. The natural composition for arthritis as claimed in
claim 1, wherein the said herbal constituents are in the
extract form.
3. The natural composition far arthritis as claimed in
claim 1, wherein the said pharmaceutically acceptable safe
inert adjuvants are selected from but not limited to diluents
like lactose, sucrose, cellulose, microcrystalline cellulose,
tribas.ic calcium phosphate, maltodextrin, or the like;
disintegrating agents like starch, sodium starch glycolate,
crospovidone, croscarmellose sodium; lubricants like
magnesium stearate, calcium stearate, talc, or the like;
glidants like colloidal silicone dioxide or the like; coating
agents like eudragit, hydroxyethyl cellulose, hydroxypropyl
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cellulose, hydroxypropyl methyl cellulose or the like; and or
other adjuvants known in the field of the art.

4. The natural composition for arthritis as claimed in

claim 1, wherein the said pharmaceutically safe inert adjuvants are included in an amount ranging from 0.1 % to 50 % weight by weight per unit dosage form.
5. The natural composition for arthritis as claimed in
claim 1, wherein the said oral dosage forms are selected from
but not limited to tablets, capsules, granules, powders,
effervescent preparations, teas or the like.
6. Process for preparation of the natural composition for
arthritis comprising of herbal constituents for synergistic
effect like Commiphora mukul 25 mg to 500 mg, Cedrus deodara
50 mg to 500 mg, Boerhaavia diffusa 50 mg to 500 mg, Zingiber
officinale 25 mg to 250 mg, Pluchea lanceolata 25 mg to 250
mg, Withania somnifera 50 rng to 500 mg, Ricinus communis 10
mg to 250 mg or the like and pharmaceutically inert safe
adjuvants in oral dosage form with better shelf- life and
stability, useful in osteoarthritis, rheumatic pain, and
joint Plains, especially for improving mobility in the
persons in the need thereof in which process steps comprises
of; mixing all the active herbal ingredients and sifting
through 20 mesh British standard sieve; mixing of herbal
ingredients with excipients like diluents, disintegrant,
glidant or the like, already passed through 40 mesh British
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standard sieve for 10 - 30 minutes; blending of active .ingredient and excipients; lubricating the blend with lubricating agent; compressing the lubricated blend into tablets using suitable dies and punches; coating of the core tablets using cellulosic or other suitable polymeric material; or filling the blend into capsules or sachets or the like.
7. Process for preparation of the natural- composition
for arthritis as claimed in claim 6, wherein the said herbal
ingredients are in the extract form.
8. Process for preparation of the natural composition
for arthritis as claimed in claim 6, wherein the said
pharmaceutically acceptable safe inert adjuvants are selected
from but not limited to diluents like lactose, sucrose,
cellulose, microcrystalline cellulose, tribasic calcium
phosphate, maltodextrin, or the like; disintegrating agents
like starch, sodium starch glycolate, crospovidone,
croscarmellose sodium; lubricants like magnesium stearate,
calcium stearate, talc, or the like; glidants like colloidal
silicone dioxide or the like; coating agents like eudragit,
hydroxyethyl cellulose, hydroxypropyl cellulose,
hydroxypropyl methyl cellulose; and or other adjuvants known
in the field of the art.
9- Process for preparation of the natural composition for arthritis as claimed in claim 6, wherein the said
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pharmaceutically inert safe adjuvants are included in an amount ranging from 0.1 % to 50 % weight by weight per unit dosage form.
10. Process for preparation of the natural composition
for arthritis as claimed in claim 6, wherein the said oral
dosage forms are selected from but not limited tablets,
capsules, granules, powders, effervescent preparations, teas
or the like.
11. The natural composition for arthritis and process for
preparation thereof as claimed in claim 1 to' 10 and as
substantially described herein and illustrated with all the
examples.

To :
The Controller of Patents Patents Office Branch, at Mumbai - 400 013

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