FIELD OF THE INVENTION
The present invention relates to herbal pain killer compositions, more particularly to herbal compositions comprising Valeriana wallichi extract and Salix alba extract as the active ingredients in an effective amount.
BACKGROUND OF THE INVENTION
People of all ages, genders and races suffer at some point from various types of pain. This ranges from general muscle aches and headaches, to significant pain from arthritis, acute injuries, surgery related pain as well as pain from chronic conditions. Chronic pain is the leading cause of adult disability in the United States and is one of the most common reasons for patient visits to primary care clinicians. (Leigh J P, Markowitz S B, Fahs M, Shin C, Landrigan P J. Occupational injury and illness in the United States: estimates of costs, morbidity, and mortality. Arch Intern Med 1997; 157:1557-68.)
Pain and alleviation of pain constitute critical challenges to present day medicine. Most people deal with pain by reaching out for over the counter (OTC) drugs (e.g., Acetaminophen) or non steroidal anti-inflammatory drugs (NSAIDs) (e.g., Ibuprofen, Naproxen) COX-2 inhibitors (e.g., Celebrex) etc. While there is less clarity on how exactly the pain-killing drugs work, it has been known that damaged or inflamed body tissues produce a variety of chemicals that send signals via the nervous system to the brain, which registers these signals as pain. Different kinds of painkillers work at different points in this process. Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, appear to act at the point of injury by blocking an enzyme needed to produce inflammatory chemicals. Paracetamol, on the other hand, acts in the brain itself to block the production of pain-causing chemicals called prostaglandins. Because of widespread use of NSAIDs and COX-2 inhibitors, the risks associated with their use are of increasing concern.
Although usually effective and frequently used, the NSAIDs offer several disadvantages if they are used on a frequent or long-term basis. Gastrointestinal safety continues to be a high priority for patients and clinicians when choosing an NSAID treatment for pain. The NSAIDs typically cause stomach upset, ulceration and bleeding in the stomach is very common. Their long-term use may cause kidney disorders. Long-term use of NSAIDs may weaken the intestinal barrier. This allows allergenic substances to pass that may actually promote inflammation in the joints. Further, they are capable of causing tiny pinpoint perforations in the surface of the small intestine. This can induce "leaky gut syndrome," which is thought to be part of the mechanism of allergy, autoimmune disease, and even arthritis itself.
COX-2 inhibitors have demonstrated improved gastrointestinal tract safety over traditional NSAID drugs. COX-inhibitors are known to slow down the rate of protein synthesis which negatively effects muscle tissue repair. They almost completely stop the function of tenocytes, which are the cells in the body that produce packed, arrayed collagen, the material that becomes connective tissue, tendons, ligaments, etc. They are also known to impede bone re-calcification, hence, are not recommended in case of fractures. The negative cardiotoxic effects of COX-2 inhibitors have been well documented in the Vioxx Gastrointestinal Outcomes Research (VIGOR) trial and Celecoxib Long-term Arthritis Safety Study (CLASS).
As the population ages, more patients will experience osteoarthritis, rheumatoid arthritis, chronic back pain, chronic musculoskeletal injuries, and migraines. It is therefore very likely that gastrointestinal problems will continue to increase as the use of the traditional nonselective NSAIDs increases because of the concern for cardiovascular complications associated with the COX-2 inhibitors. The elderly are especially at risk for gastrointestinal events, including serious complications. Therefore there remains a need for just as effective, but safer alternatives for the treatment of pain.
Many anecdotal as well as recent studies support the use of natural remedies (herbal) for relief of pain. Historically, herbal remedies have not only been reported as effective, but they have been used to treat various ailments and conditions and generally have had very low risk profiles. But such remedies are not typically as effective as pharmaceutical pain relief products that are currently available over the counter (OTC) or by prescription. Therefore there remains a need to explore natural ingredients for treatment of pain in mammals.
Many herbal pain relieving compositions are known in the prior art. U.S. publication US 2011/0076327 A1 discloses a herbal pain killer composition, comprising 50 mg of each of the following ingredients combined into an approximately 600 mg tablet for oral administration to a mammal: Boswellia serrata, Tumeric, White Wilow, Harpagophytum procumbens, Phellodendron amurense, Paullinia tomentosa, Milkberry, Mimosa pudica, Lactuca virosa, Naringen, 6-7 Dihydroxybergamottin, and Yerba mate.
Further, U.S. publication US 2011/0117175 A1 discloses a pain reliever composition A comprising dextrose, aloe vera concentrate, and some or all of the following ingredients: propylene glycol, caprylic/capric tryglicerides, sodium chloride (or acetic acid), a homeopathic anti-inflammatory extract, Dimethyl Sulfone (or Methylsulfonylmethane (MSM)), cetyl myristoleate, and a pitcher plant extract.
Despite herbal medicines becoming more popular due to their relative safety over synthetic drugs, nevertheless, there are problems associated with herbal medications, and their use requires knowledge of their biological action, clinical studies, and potential interactions with other OTC and prescription medications. Hence there is a need in the art for herbal painkiller compositions that are not only free from the aforementioned drawbacks but also provide relief from a broad spectrum of pains and aches.

SUMMARY OF THE INVENTION
The present invention is broadly related to a herbal pain killer composition for providing relief from various types of pain such as headache, migrane, toothache, menstrual cramps, muscle aches, post operative surgical pain, strains, sprains, inflammation, chronic pain, rheumatic pain, shin pain and so forth.
In accordance with an embodiment of the invention, there is provided a herbal pain killer composition, comprising:
(a) an extract of Tagar (Valeriana wallichi); and
(b) an extract of Salix (Salix alba);
In accordance with another embodiment of the invention the ratio of the extract of Tagar (Valeriana wallichi) to the extract of Salix (Salix alba) is in the range from 1:1 to 1:4.
In accordance with another embodiment of the invention, the herbal pain killer composition comprises the extract of Tagar in an amount of 8.33-16.67%, the extract of Salix in an amount of 16.67-33.33% and a plurality of pharmaceutically acceptable excipients.
In accordance with another embodiment of the invention, the excipients in the herbal pain killer composition are selected from the group consisting of a diluent, a disintegrant, an anti-microbial preservative, a glidant, a lubricant, a film coating material and combinations thereof and the composition is in the form of a tablet.
In accordance with yet another embodiment of the invention, the diluent is present in an amount of 68.22-34.68%, the disintegrant is present in an amount of 2-10%, the anti-microbial preservative is present in an amount of 0.10-0.40%, the glidant is present in an amount of 0.25-1% and the lubricant is present in an amount of 0.25-1%.
In accordance with still another embodiment of the invention, the film coating material is selected from the group consisting of coating ready-mix, ethyl cellulose, hydroxyl propyl methyl cellulose, shellac, diethyl phthalate, talc, colouring agents, and combinations thereof and present in an amount of 2.08-2.92%.
In accordance with another embodiment of the invention, there is provided a process for preparing a tablet of the herbal pain killer composition, comprising the steps of: (a) weighing and mixing the extract of Tagar, the extract of Salix, the diluent and methylparaben in a mixing vessel to form a mixture; (b) weighing and mixing sodium benzoate, the glidant, the lubricant and the disintegrant in a mixing vessel to form a mixture; (c) mixing the mixture of step (a) and the mixture of step (b) to form another mixture; (d) compressing the mixture of step (c) into an un-coated tablet by a suitable compressing machine; and (e) coating the un-coated tablet with the film coating material to obtain the tablet of the herbal pain killer composition.
DETAILED DESCRIPTION OF THE INVENTION
Discussed below are some representative embodiments of the present invention. The invention in its broader aspects is not limited to the specific details and representative methods. The illustrative examples are described in this section in connection with the embodiments and methods provided. The invention according to its various aspects is particularly pointed out and distinctly claimed in the attached claims read in view of this specification.
It is to be noted that, as used in the specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, a reference to a composition containing “a compound” includes a mixture of two or more compounds. It should also be noted that the term “or” is generally employed in its sense including “and/or” unless the content clearly dictates otherwise.
The expression of various quantities in terms of “%” or “% w/w” means the percentage by weight of the total solution or composition unless otherwise specified.
All cited references are incorporated herein by reference in their entireties. Citation of any reference is not an admission regarding any determination as to its availability as prior art to the claimed invention.
The present invention, in its product and process aspects, is described in detail as follows:
Valeriana wallichi (also known as Indian Valerian, Tagar) grows wild in the temperate Himalayas at an altitude of 1500-3000 m and is an ingredient of herbal medicines in Indian systems of medicine. Valeriana wallichi is a counterpart of European V. officinalis L. the official drug in the British and European Pharmacopoeias. Roots and rhizomes of Valeriana wallichi are highly aromatic, contain valepotriates and essential oils, both perhaps contributing towards its bioactivity. In addition, sesquiterpenoids, monoterpenoids, lignans and alkaloids with pharmacological properties have been reported in valerian. The V. wallichi essential oil has been the subject of previous studies which established the existence of three distinct chemotypes. Isolation of valepotriates from Valeriana wallichi and their bioactivity studies have also been reported. There is a preliminary report showing analgesic effect of dried leaves of V. jatamansi at a dose of 2 mg. Valerian is also used for muscle and joint pain. Some women use valerian for menstrual cramps and symptoms associated with menopause, including hot flashes and anxiety. Sometimes, valerian is added to bath water to help with restlessness and sleep disorders.
Salix alba (also known as white willow bark) contains tannin as its chief constituent, as well as a small amount of salicin. It is frequently administered as a painkiller and is believed to be a natural precursor to aspirin. It is commonly used to treat rheumatism, fever, headaches and pain caused by inflammation.
Although Tagar (Valeriana wallichi) and Salix (Salix alba) are individually known to provide relief from certain types of pain, it would be beneficial to provide a painkiller composition that is effective against a broad spectrum of pain and aches.
Hence the objective of the present invention is to develop an alternative form of pain relief composition utilizing. extract of Tagar (Valeriana wallichi) and Salix (Salix alba) as active ingredients.
Accordingly, the present inventors have developed a herbal pain killer composition, which is free from the side effects associated with synthetic drugs, comprising an extract of Tagar (Valeriana wallichi); an extract of Salix (Salix alba); and a plurality of pharmaceutically acceptable excipients; wherein the ratio of the extract of Tagar (Valeriana wallichi) to the extract of Salix (Salix alba) ranges from 1:1 to 1:4. The term “pharmaceutically acceptable excipients” used herein refers to physiologically inert additives that are routinely used in pharmaceutical dosage forms.
The herbal pain killer composition of the present invention is formulated in the form of a tablet, wherein the excipients include a diluent, a disintegrant, an anti-microbial preservative, a glidant, a lubricant, and a film coating material. The tablet contains the extract of Tagar (Valeriana wallichi) and the extract of Salix (Salix alba) in the ranges from 8.33-16.67% and 16.67-33.33% respectively
An important constituent of any tablet is a diluent, also called as filler, which is often added to provide better tablet properties, such as improved cohesion, improved compression manufacturing and adjusting weight of the tablet as per dye capacity. Non-limiting examples of the diluents that can be used in the present invention include micro-crystalline cellulose, dibasic calcium phosphate, starch, magnesium carbonate, calcium carbonate, lactose and so forth, each of which can be used individually or in combination, in an amount in the range from 68.22-34.68%. Micro-crystalline cellulose (MCC) is purified partially depolymerized cellulose, prepared by treating a-cellulose with mineral acids. It is a white, crystalline powder composed of agglomerated porous microfibers. After purification by filtration and spray-drying, porous microcrystals are obtained.
A disintegrant is always added to a tablet to induce breakup of the tablet when it comes in contact with aqueous fluid and this process of desegregation of constituent particles before the drug dissolution occurs, is known as disintegration process. Non-limiting examples of the disintegrants that can be used in the present invention include croscarmellose sodium, crospovidone, sodium starch glycolate, polacrillin potassium, and so forth, each of which can be used individually or in combination in an amount in the range from 2.00-10.00%. Croscarmellose sodium is an internally cross-linked sodium carboxymethylcellulose, wherein the cross-linking reduces water solubility while still allowing the material to swell (like a sponge) and absorb many times its weight in water, thereby accelerating the dissolution of the tablet. Crospovidone (cross linked polyvinyl N-pyrrolidone) is an inert and insoluble white to light yellow free-flowing powder. It has hygroscopic, or water-attracting properties with excellent swelling characteristics. It is this swelling characteristic that makes it useful as a disintegrant in pharmaceutical dosage forms.
Another important constituent of the tablet formulation is an anti-microbial preservative, which is added to increase the shelf life of the pharmaceutical substance by preventing the growth of microorganisms. Non-limiting examples of the anti-microbial preservatives that can be used in the present invention include, potassium sorbate, sodium benzoate, sodium methylparaben, methylparaben, benzoic acid, sorbic acid and so forth, each of which can be used individually or in combination. The tablet contains the anti-microbial preservative in an amount in the range from 0.1-0.40%.
A glidant is often added to the tablet formulation to improve the flow properties of the material which is to be fed into the die cavity and aid in particle rearrangement within the die during the early stages of compression. Non-limiting examples of glidants that can be used in the present invention include colloidal silicon dioxide, starch, talc, and so forth, each of which can be used individually or in combination, in an amount in the range from 0.25-1.00%.
It is recommended to add lubricants to the herbal formulation as they reduce friction by interposing an intermediate layer between the tablet constituents and the die wall during compression and ejection. Non-limiting examples of the lubricants that can be used in the present invention include magnesium stearate, sodium stearyl fumarate, polyethylene glycol 6000 and so forth, each of which can be used individually or in combination, in an amount in the range from 0.25-1.00%.
Finally, the un-coated tablet is coated with an appropriate film coating material for protecting unstable compositions, protection in the stomach against enzymes and acids, improving the appearance of the tablet, and masking objectionable odours and taste. Non-limiting examples of the film coating material that can be used in the present invention for coating un-coated tablets, include coating ready-mix, ethyl cellulose, hydroxyl propyl methyl cellulose, shellac, diethyl phthalate, talc, colouring agents, and so forth, each of which can be used individually or in combination, in an amount in the range from 2.08-2.92%. The coating ready-mix comprises of hydroxyl propyl methyl cellulose, diethyl phthalate, ethyl cellulose, talc, titanium dioxide, lake ponceau 4R, and lake sunset yellow. Prior to coating the un-coated tablets, the coating ready-mix was dispersed in isopropyl alcohol for approximately 5 minutes. Thereafter, methylene chloride was added and stirred for approximately 45 minutes and filtered through a nylon cloth to prepare the non-aqueous coating dispersion, which was finally used to coat the un-coated tablets.
The present invention is more particularly described in the following non-limiting examples that are intended as illustrations only since numerous modifications and variations within the scope of the present invention will be apparent to a skilled artisan. Unless otherwise noted, all parts, percentages, and ratios reported in the following examples are on a weight basis, and all reagents used in the examples were obtained or made available from the chemical suppliers.
Process for preparing Tagar (Valeriana wallichi) extract.
The herb was extracted with ethyl acetate (herb to solvent in a ratio of 1:4) over a period of 2 to 3 hours at a temperature of 65-70 °C. The extraction process was repeated four times and the combined extracts were concentrated under vacuum to afford a viscous liquid. Finally, the viscous liquid was filtered and spray dried to obtain powdered extract.
Process for preparing Salix (Salix alba) extract.
The herb was extracted with hot water (herb to solvent in a ratio of 1:10) over a period of 30 min at a temperature of 100 °C. The extraction process was repeated thrice and the decoction so obtained was concentrated at 80 °C, filtered, dried and sieved through 60# mesh to obtain powdered extract.
Examples 1 and 2
Table 1. illustrates the ingredients and their amounts present in the tablet of the herbal pain killer composition. The unit of each value is percent by weight.
Table 1.Herbal pain killer tablet formulation
No Ingredients Example 1 Example 2
1 Extract of Tagar (Valeriana wallichi) 10 14.58
2 Extract of Salix (Salix alba) 20 29.17
3 Microcrystalline cellulose 59.3 44.85
4 Methylparaben 0.1 0.2
5 Sodium benzoate 0.1 0.2
6 Colloidal silicon dioxide 0.5 0.75
7 Magnesium stearate 0.5 0.75
8 Croscarmellose sodium 2.5 4.5
9 Crospovidone 4.5 2.5
10 Coating ready-mix 2.5 2.5
Process for preparing a herbal pain killer composition in the form of a tablet.
The amounts of ingredients used in preparing the tablets of the herbal pain killer compositions are presented in Table 1. Extract of Tagar (Valeriana wallichi), Extract of Salix (Salix alba), micro-crystalline cellulose and methylparaben were sieved through a mesh of size 30, weighed and mixed in a mixing vessel to form a first mixture. Sodium benzoate, colloidal silicon dioxide, magnesium stearate, croscarmellose sodium, and crospovidone were sieved through a mesh of size 60, weighed and mixed in a mixing vessel to form a second mixture. The first mixture and the second mixture were mixed to form a third mixture. The third mixture was compressed into un-coated tablets using a suitable compressing machine, such as a tableting machine. The term “tableting machine” used herein refers to a machine that compresses powders or mixtures into tablets of uniform shape and size. The un-coated tablets were finally coated with a non-aqueous coating dispersion, in a suitable coating pan, to obtain the tablet of the herbal pain killer composition.

In vivo and In vitro studies
Evaluation of the analgesic and anti-inflammatory activity of the herbal pain killer composition in Wister Albino rats.
The analgesic activity of the herbal pain killer composition was evaluated by the acetic acid induced writhing reflex method. The rats were divided into four groups, i.e. Group 1, Group 2, Group 3 and Group 4, having five animals each. Group 1, which served as control, was administered normal saline (10 mL/kg). Group 2 was administered low (50 mg/kg, p.o) doses whereas Group 3 was administered high (100 mg/kg, p.o) doses of the herbal pain killer composition, i.e. Example 1. The term “mg/kg, p.o” refers to mg per kg of body weight, taken orally. Group 4 was administered the standard drug, Indomethacin (10 mg/kg, p.o). One hour after the administration of the herbal pain killer composition and the standard drug, the rats were administered acetic acid intraperitonially and thereafter the number of writhing movements was recorded for a period of 30 min.
Group 1, which was administered low doses (50 mg/kg, p.o) of the herbal pain killer composition, showed a 28% reduction in writhing reflex. Inhibition of writhing reflex was significantly higher, i.e. 86%, in Group 3, which was administered high doses (100 mg/kg, p.o) of herbal pain killer. Notably, the standard drug (Indomethacin) inhibited the writhing reflex in Group 4 animals to an extent of 94.43%. In conclusion, reduced writhing response indicates good analgesic activity of the herbal pain killer composition.
Further, the anti-inflammatory activity of the herbal pain killer composition (Example 1) was evaluated by the Carrageenan induced paw edema method. The animals were again divided into four groups of 5 animals each, i.e. Group 1, Group 2, Group 3 and Group 4, and initial paw volumes of all animals were measured using a plethysmometer. Group 1, which served as control, was administered normal saline (10 mL/kg). Group 2 was administered low (50 mg/kg, p.o) doses whereas Group 3 was administered high (100 mg/kg, p.o) doses of the herbal pain killer composition, i.e. Example 1. Group 4 was administered the standard drug, Indomethacin (10 mg/kg, p.o). Edema was observed 30 min after subplantar injection of 100 µl of 1% freshly prepared solution of carrageenan in distilled water.
Percentage inhibition of paw edema was calculated at 1 h, 2 h and 3 h time points. At 1 h time point, 16.19% and 25.79% mean inhibition of paw edema was observed in Group 2 (50 mg/kg, p.o) and Group 3 (100 mg/kg, p.o) respectively, whereas Group 4 treated with the standard drug, Indomethacin (10 mg/kg, p.o), showed 32.98% inhibition. This anti-inflammatory effect almost doubled at 2 h time point for both Group 2 and Group 3, whereas the inhibition was 1.5 times for Group 4. Moreover, at 3 h time point, there was a further increase in anti-inflammatory activity as evidenced by the inhibition of 53.51%, 70.55%, and 75.75% for Group 2, Group 3 and Group 4 respectively. In conclusion, the results indicate that the herbal pain killer composition (Example 1) exhibited good anti-inflammatory activity.

Inhibition of TNF-a, NO, 5-LOX, COX-1 and COX-2 by the herbal pain killer composition.
In-vitro studies were carried out in order to determine the inhibitory effect of the herbal pain killer composition (Example 1) on inflammatory markers such as, TNF-a, NO, 5-LOX, COX-1 and COX-2.
For cell based assay, 200 mg/mL stock solution of the herbal pain killer composition of the present invention, i.e. Example 1, was prepared in 50% ethanol. The stock solution was used for preparation of subsequent dilutions in serum free medium to achieve working dilutions ranging from 1 ng/mL – 500 µg/mL. The concentration range tested for NO assay was 0.001 – 10 µg/mL, whereas that for TNF-a assay was 0.001 – 1 µg/mL. The assays were performed on RAW264.7 cells.
Cells were counted on a hemocytometer and a single cell suspension was prepared. 0.4 × 106 cells/well were seeded in a 6 well culture plate in DMEM + 10% FBS. Cells were incubated in a CO2 incubator for 24 h at 37 °C, 5% CO2 and 95% humidity. Cells were treated with the herbal pain killer composition of the present invention, i.e. Example 1, in the concentration range of 0.001 µg/mL to 1 µg/mL (for TNF-a) and 0.001 µg/mL to 10 µg/mL (for NO) in the presence and absence of Lipopolysaccharide (LPS) (1 µg/mL) for a time period of 24 h. Cells treated with LPS and ethanol served as control whereas those treated with Dexamethasone (0.01 – 10 µg/mL) served as positive control. The supernatants were collected after 24 h to estimate the effect of the herbal pain killer composition of the present invention (Example 1) on the inflammatory markers, i.e. TNF-a and NO.
The levels of TNF-a were determined using mouse TNF-a ELISA kit (R&D systems, Catalogue number MTA00B) as per manufacturer’s instructions. These assays employ the quantitative sandwich enzyme immunoassay technique. 50 µL of assay diluent was added to each well. 50 µL of standards and supernatant samples were pipetted into the wells and incubated for 2 h at room temperature. Mouse antigen present in either of the samples was bound by the immobilized antibody. Wells were washed 5 times using wash buffer. After washing away any unbound substances, 100 µL of mouse TNF-a conjugate was added to the wells and incubated for 2 h at room temperature. Wells were again washed five times using wash buffer. 100 µL of substrate solution was added to the wells and incubated for 30 min at room temperature in dark. 100 µL of stop solution was added to the wells. The intensity of the color was measured at 450 nm. The OD is proportional to the amount of cytokine bound in the initial step. Concentration of each cytokine/chemokine (pg/mL) was then determined from the standard curve. Percentage inhibition of TNF-a activity was calculated as : [{TNF-a levels in RAW264.7 cells (Control) – TNF-a levels in RAW264.7 cells treated with test items}/TNF-a levels in RAW264.7 cells (Control)]*100
The levels of NO were estimated using Griess Reagent, which was prepared by mixing equal volumes of 1% Sulfanilamide in 5% phosphoric acid and 0.1% NED (N-(1-Naphthyl)ethylenediamine dihydrochloride) in MilliQ water. 100 µL of supernatents collected were incubated with 100 µL of Griess reagent and incubated for 30 min in dark. The ODs were read at 548 nm.
For cell free assay, 200 mg/mL stock solution of the herbal pain killer composition of the present invention, i.e. Example 1, was prepared in Di methyl sulfoxide (DMSO). The stock solution was used for preparation of subsequent dilutions in assay buffer to achieve working dilutions ranging from 1 µg/mL – 2 mg/mL. The inhibition of 5-LOX enxyme by the herbal pain killer composition was evaluated by using Cayman’s Lipoxygenase Inhibitor Screening Assay Kit, 760700. 90 µL of 5-LOX enzyme and 10 µL of different concentrations of the herbal pain killer composition of the present invention and vehicle control were added to their corresponding wells. DMSO treated well was considered as vehicle control. The reaction was initiated by addition of substrate (10 µL) and placing the 96-well plate on a shaker for 5 min. 100 µL of chromogen was added to each well to stop the enzyme catalysis and the plate was placed on shaker for 5 min to develop the reaction. The absorbance was read at a wavelength of 490 nm. Trolox was used as positive control for 5-LOX assay.
The inhibition of COX-1 and COX-2 enzymes by the herbal pain killer composition of the present invention (Example 1) was evaluated using Caymen’s COX inhibitor screening assay kit as described in - Smith, C.J., Zhang, Y., Koboldt, C.M., et al. Pharmacological analysis of cyclooxygenase-1 in inflammation. Proc Natl Acad Sci USA 95 13313-13318 (1998).
Herbal pain killer composition demonstrated remarkable inhibition of Lipopolysaccharide (LPS) stimulated TNF-a and mild inhibition of LPS stimulated Nitric oxide (NO) secretion in mouse macrophages (RAW264.7 cells). The herbal pain killer composition also demonstrated mild inhibition of 5-LOX activity. The herbal pain killer composition (Example 1) was also able to inhibit COX-1 and COX-2 with IC50 values of 41.06 µg/mL and 56.24 µg/mL respectively. Thus, it could be concluded that the herbal pain killer composition of the present invention had potent but non selective COX inhibition activity.
While particular embodiments of the present invention have been illustrated and described, it would be obvious to those skilled in the art that various other changes and modifications can be made without departing from the spirit and scope of the invention. It is thereof intended to cover in the appended claims such changes and modifications that are within the scope of the invention.

CLAIMS:
We claim:
1. A herbal pain killer composition, comprising:
(a) an extract of Tagar (Valeriana wallichi); and
(b) an extract of Salix (Salix alba).
2. The herbal pain killer composition, as claimed in claim 1, wherein the ratio of the extract of Tagar (Valeriana wallichi) to the extract of Salix (Salix alba) is in the range from 1:1 to 1:4.
3. The herbal pain killer composition, as claimed in claims 1 or 2, wherein the extract of Tagar is present in an amount of 8.33-16.67%, the extract of Salix is present in an amount of 16.67-33.33% and the composition further comprises pharmaceutically acceptable excipients.
4. The herbal pain killer composition, as claimed in claim 3, wherein the excipients are selected from the group consisting of a diluent, a disintegrant, an anti-microbial preservative, a glidant, a lubricant, a film coating material and combinations thereof, and the composition is in the form of a tablet.
5. The herbal pain killer composition, as claimed in claim 4, wherein the diluent is selected from the group consisting of microcrystalline cellulose, dibasic calcium phosphate, starch, magnesium carbonate, calcium carbonate, lactose and combinations thereof and present in an amount in the range from 68.22-34.68%.
6. The herbal pain killer composition, as claimed in claim 4, wherein the disintegrant is selected from the group consisting of croscarmellose sodium, crospovidone, sodium starch glycolate, polacrillin potassium, and combinations thereof and present in an amount in the range from 2-10%.
7. The herbal pain killer composition, as claimed in claim 4, wherein the anti-microbial preservative is selected from the group consisting of potassium sorbate, sodium benzoate, sodium methylparaben, methylparaben, benzoic acid, sorbic acid and combinations thereof, and present in an amount in the range from 0.10-0.40%.
8. The herbal pain killer composition, as claimed in claim 4, wherein the glidant is selected from the group consisting of colloidal silicon dioxide, starch, talc and combinations thereof and present in an amount in the range from 0.25-1%.
9. The herbal pain killer composition, as claimed in claim 4, wherein the lubricant is selected from the group consisting of magnesium stearate, sodium stearyl fumarate, polyethylene glycol 6000 and combinations thereof and present in an amount in the range from 0.25-1%.
10. The herbal pain killer composition, as claimed in claim 4, wherein the film coating material is selected from the group consisting of coating ready-mix, ethyl cellulose, hydroxyl propyl methyl cellulose, shellac, diethyl phthalate, talc, colouring agents, and combinations thereof and present in an amount in the range from 2.08-2.92%.