PAIN RELIEVING HERBAL TOPICAL GEL
Technical Field of Invention
The present invention relates to a pain relieving herbal topical dosage form and the process of preparation of the same. More particularly the present invention relates to a pain relieving herbal topical gel composition comprising boswellia gum extract, capsicum oleoresin and one or more other analgesic and anti-inflammatory agents and the process of preparation of the same.
Background of the Invention
Several topical dosage forms like creams, ointments, liniments, lotions and gels have been utilized for the relief of the pains due to localized inflammatory conditions including sprains, strains, bruises, tenosynovitis, myositis, bursitis, sports injuries, low back pain, localized form of soft tissue rheumatism, traumatic inflammation of tendons, muscles and joints, osteoarthritis, frozen shoulder, cervical spondylitis etc. Most of these topical dosage forms contain as the active ingredient, the non-steroidal anti-inflammatory agents like nimesulide, ketoprofen and diclofenac. However, all of these localized inflammatory conditions resulting in pain are the subject of continuing research looking for better treatments. For example, treatments utilizing herbal compositions can benefit many patients and provide advantages not otherwise available. Hence it would be advantageous to formulate a pain relieving herbal topical gel.
The gum extract of the plant Boswellia serrata (Family: Burseraceae) has long been in use for the treatment of gout and rheumatoid arthritis by the Ayurvedic medicine practitioners in the Indian system of medicine. The boswellia gum extract is a complex mixture of various terpenoids, polysaccharides and inorganic salts. It has now been established that the antiinflammatory activity of the boswellia gum extract is due to the presence of certain triterpenoids commonly known as boswellic acids. Boswellic acids inhibit proinflammatory 5-lipoxygenase chemicals and blocks leukotriene synthesis. By doing so, boswellia may be helpful in medical conditions involved in inflammation.
Capsicum oleoresin has been recognized by the FDA as an effective over the counter topical analgesic for the temporary relief of minor aches and pains of muscles and joints associated with arthritis, simple backache, strains, bruises and sprains. Capsicum provides relief by selectively binding to a protein known as TRPV1 that resides on the membranes of pain and heat sensing neurons and depleting presynaptic substance P, a neuropeptide involved in the transmission of pain impulses from the periphery to the central nervous system.
The US patent 5178879 discloses a clear, water soluble, non-greasy gel consisting essentially of about 0.025% to about 0.075% capsaicin, about 0.5% to about 2% of a carboxypolymethylene emulsifying agent, about 30% to about 45% ethyl alcohol and about 55% to about 70% water. The PCT application WO09092040 discloses a topical formulation comprising one or more analgesic agents and a plurality of skin penetrants. The PCT application discloses the one or more analgesic compounds as selected from the group consisting of methyl salicylate, salicylic acid, menthol, benzocaine, capsaicin, y-linoleic acid, a-boswellic acid, B-boswellic acid, 11-keto-S-boswellic acid, ginger extract, aloe vera extract, and combination thereof.
The present invention relates to a pain relieving herbal topical gel composition comprising boswellia gum extract, capsicum oleoresin and one or more other analgesic and antiinflammatory agents and the process of preparation of the same.
Summary of the Invention
In one general aspect it relates to a pain relieving herbal topical gel composition wherein the topical gel composition comprises of boswellia gum extract, capsicum oleoresin, one or more other analgesic and anti-inflammatory agent(s) and one or more pharmaceutical^ acceptable excipients.
In another general aspect it relates to a pain relieving herbal topical gel composition wherein the topical gel composition comprises of boswellia gum extract, capsicum oleoresin, one or more other analgesic and anti-inflammatory agent(s) and one or more pharmaceutically acceptable excipients wherein the amount of boswellia gum is from about 0.01% to 25% by weight and the amount of capsicum oleoresin is from about 0.001% to 10% by weight.
In another general aspect it relates to a pain relieving herbal topical gel composition wherein the topical gel composition comprises of boswellia gum extract, capsicum oleoresin, one or more other analgesic and anti-inflammatory agent(s) and one or more pharmaceutically acceptable excipients wherein other analgesic and anti-inflammatory agents are selected from the group comprising of salicylate analgesics, rubefacients, counterirritants, herbal analgesics or anti-inflammatory agents and non-steroidal anti-inflammatory agents.
In another general aspect it relates to a pain relieving herbal topical gel composition wherein the topical gel composition comprises of boswellia gum extract, capsicum oleoresin, one or
more other analgesic and anti-inflammatory agent(s) and one or more pharmaceutically acceptable excipients wherein pharmaceutically acceptable excipients are selected from the group comprising of gel forming agents, humectants, skin permeation enhancers, neutralizing agents, surface-active agents, preservatives and solvents.
In another general aspect it relates to a pain relieving herbal topical gel composition wherein the topical gel composition comprises of boswellia gum extract, capsicum oleoresin, one or more other analgesic and anti-inflammatory agent(s) and one or more pharmaceutically acceptable excipients wherein other analgesic and anti-inflammatory agents are selected from the group comprising of methyl salicylate, menthol, clove oil, linseed oil and seasame oil wherein pharmaceutically acceptable excipients are selected from the group comprising of isopropyl alcohol, benzyl alcohol, glycerin, propylene glycol, polysorbate, cresmer, diethyl amine, triethanolamine and carbomer.
In another general aspect it relates to a process of preparing a pain relieving herbal topical gel composition comprising of boswellia gum extract, capsicum oleoresin, one or more other analgesic and anti-inflammatory agent(s) and one or more pharmaceutically acceptable excipients wherein the process comprises of the following steps:
A.
I. one or more of boswellia gum extract, capsicum oleoresin, other analgesic and antiinflammatory agents and optionally preservative(s) are mixed together to form a blend.
B.
I. a solvent is optionally heated and is mixed with one or more of pharmaceutically acceptable excipients selected from gel forming agents, humectants, skin permeation enhancers, surface-active agents, preservatives and solvents and one or more other analgesic and anti-inflammatory agents selected from the group comprising of salicylate analgesics, rubefacients, counterirritants, herbal analgesic or anti-inflammatory agents and nonsteroidal anti-inflammatory agents under constant homogenization to form a homogeneous mixture.
II. a neutralizing agent is added to the homogeneous mixture of step (I) to form homogeneous blend.
C.
I. the blend obtained from step A is mixed with homogeneous blend obtained from step B to form a homogeneous gel.
Detailed Description of the Invention
The term "gel" as used herein refers to a semisolid system in which a liquid phase is constrained within the crosslinked matrix of drug substance and/or excipients. The drug substance and/or excipients may be either dissolved or suspended within the liquid phase.
The term "pain" as used herein refers to pains due to localized inflammatory conditions including sprains, strains, bruises, tenosynovitis, myositis, bursitis, sports injuries, accidental injuries, low back pain, musculoskeletal disorder, localized form of soft tissue rheumatism, traumatic inflammation of tendons, muscles and joints, osteoarthritis, rheumatoid arthiritis, gout, frozen shoulder and cervical spondylitis.
The term "boswellia gum extract" as used herein refers to a solution of the resin extracted from the herb of the plants of genera Boswellia, Commiphora, and Bursera of the family Burseraceae by an extraction process wherein the crude herbal material is contacted with an appropriate solvent to remove the resins desired to be extracted from the material. Such an extraction can be carried out by any conventional process known in the art. The effective amount of boswellia gum used comprises from about 0.01% to 25%, particularly from about 0.1% to 15%, and more particularly from about 1% to 10% by weight.
The term "capsicum oleoresin" as used herein refers to a crude mixture of compounds, one of which is capsaicin, which may be produced by extraction of the fruit of the plant species Capsicum frutesceens L. of the family Solanaceae with appropriate solvents. The effective amount of capsicum oleoresin used comprises from about 0.001% to 10%, particularly from about 0.01% to 5%, and more particularly from about 0.01% to 1% by weight.
Other analgesic and anti-inflammatory agents may be selected from the group comprising of salicylate analgesics, rubefacients, counterirritants, herbal analgesics or anti-inflammatory agents and non-steroidal anti-inflammatory agents.
Salicylate analgesics may be selected from but are not limited to salicylic acid, methyl salicylate, glycol monosalicylate, salicylamide and dipropylene glycol salicylate and combinations thereof. The effective amount of salicylate analgesics used comprises from about 0.1% to 30%, particularly from about 1% to 20%, and more particularly from about 1% to 15% by weight.
Rubefacients may be selected from but are not limited to methyl salicylate, capsicum oleoresin, camphor, chloroform, menthol, allyl isothiocyanate and combinations thereof. The effective
amount rubefacients used comprises from about 0.001% to 30%, particularly from about 0.01% to 25%, and more particularly from about 0.01% to 20% by weight.
Counterirritants may be selected from but are not limiting to methyl salicylate, camphor, menthol, clove oil, eucalyptus oil, thymol and the like. The effective amount of counterirritants used comprises from about 0.001% to 30%, particularly from about 0.01% to 25%, and more particularly from about 0.01% to 20% by weight.
Herbal analgesic or anti-inflammatory agents may include but are not limited to herbs or herbal extracts of the plants species Cinnamomum camphora, Trachyspermum ammi, Hyoscyamus niger, Linum usitatissimum, Sesamum indicum, Datura metel, Commiphora wightii, Butea monosperma, Artemisia maritime, Myristica fragrans, Mentha arvensis, Ficus bengalensis, Sesbania grandiflora, Eugenia caryophyllata, Ocimum sanctum, Ocimum basilicum, Amorphophallus campanulatus, Berberis aristata, Vitex negundo, Carica papaya and combinations thereof.
Non-steroidal anti-inflammatory agents may be selected from but are not limited to ibuprofen, aspirin, diclofenac, naproxem and combinations thereof.
Pharmaceutically acceptable excipients may be selected from the group comprising of gel forming agents, humectants, skin permeation enhancers, neutralizing agents, surface-active agents, preservatives and pharmaceutically acceptable solvents.
Suitable gel-forming agents may include but are not limiting to carboxyvinyl polymers such as
carbomer, hydroxyethylcellulose, methylcellulose, carboxymethylcellulose,
hydroxypropylcellulose, alginic acid-propylene glycol ester and combinations thereof.
Suitable humectants may include but are not limiting to glycerin, sorbitol, propylene glycol, polyethylene glycol and combinations thereof.
Suitable skin permeation enhancers may include but are not limited to ethanol, benzyl alcohol, silicone based enhancers such as hexamethyldisiloxane and octamethyltrisiloxane, an organic acid such as oleic acid, triglyceride fatty acids, dimethyl sulfoxide, N-dodecyl pyrrolidone, decanol, dodecanol and combinations thereof.
Suitable neutralizing agents may include but are not limited to methylamine, dimethylamine, ethylamine, diethylamine, propylamine, isopropylamine, diisopropylamine, cyclohexylamine, benzylamine, guanidine, pyrrolidine, piperidine, morpholine, arginine, lysine, ethanolamine, diethanolamine, diisopropanolamine, triethanolamine and combinations thereof.
Suitable surface active agents may include but are not limited to glyceryl monooleate, polyoxyethylene sorbitan fatty acid esters such as tweens, hydrogenated vegetable oils preferably glycerol, ethylene glycol, polyethylene glycol, sorbitol, propylene glycol, sorbitan esters, benzalkonium chloride, cetrimide, sodium lauryl sulfate, cresmer and combinations thereof.
Suitable preservatives may include but are not limiting to benzyl alcohol, thimerosal, chlorobutanol, benzalkonium chloride, etradecyltrimethyl ammonium bromide (Cetrimide), sodium benzoate, thymol, methylparaben, butylparaben, propylparaben, sorbic acid, imidurea, propyl gallate, butylated hydroxyanisole, butylated hydroxytoluene, citric acid and combinations thereof.
Suitable solvents may include but are not limited to water, ethanol, isopropyl alcohol, butyl alcohol, benzyl alcohol, dimethyl sulfoxide, dimethylformamide, N-methyl-2-pyrrolidone, 2-pyrrolidone, dimethylacetamide, propylene glycol, polyethylene glycol, butylene glycol, hexylene glycol, glycerol propylene carbonate and mixtures thereof.
Gels are prepared by dissolving, dispersing, suspending or emulsifying the organic and inorganic particles in a suitable gelling base.
In one embodiment, the process for preparing a pain relieving herbal topical gel composition comprising of boswellia gum extract, capsicum oleoresin, one or more other analgesic and antiinflammatory agents and one or more pharmaceutically acceptable excipients wherein the process comprises of the following steps: A.
I. boswellia gum is mixed with solvent(s).
II. the mixture of step (I) is filtered through a suitable filter.

III. the filtrate obtained from step (II) is centrifuged to obtain a clear supernatant liquid.
IV. the clear supernatant liquid of boswellia gum extract obtained from step (III), capsicum oleoresin, other analgesic and anti-inflammatory agents and preservative(s) are mixed together to obtain the pre blend.
B.
I. a solvent is heated and is mixed with gel forming agent(s), humectant(s), skin permeation enhancer(s), surface active agent(s), and one or more other analgesic and antiinflammatory agents under constant homogenization to obtain a homogeneous mixture.
II. neutralizing agent(s) is added to the homogeneous mixture obtained from step (I) under constant stirring to obtain a homogeneous blend.
c.
I. the pre-blend obtained from step A is mixed with the homogeneous blend obtained from step B to form the homogeneous gel.
In another embodiment, the process for preparing a pain relieving herbal topical gel composition comprising of boswellia gum extract, capsicum oleoresin, one or more other analgesic and anti-inflammatory agents and one or more pharmaceutically acceptable excipients wherein the process comprises of the following steps: A.
I. boswellia gum is mixed with solvent(s).
II. the mixture of step (I) is filtered through a suitable filter.
III. the filtrate obtained from step (II) is centrifuged to obtain a clear supernatant liquid.
IV. the clear supernatant liquid of boswellia gum extract obtained from step (III), capsicum oleoresin and other analgesic and anti-inflammatory agents are mixed together to obtain the pre blend.
B.
I. a solvent is heated and is mixed with gel forming agent(s), humectants(s), skin permeation enhancer(s), surface active agent(s), preservative(s) and one or more other analgesic and anti-inflammatory agents under constant homogenization to obtain a homogeneous mixture.
II. neutralizing agent(s) is added to the homogeneous mixture obtained from step (I) under constant stirring to obtain a homogeneous blend.
C.
I. the pre-blend obtained from step A is mixed with the homogeneous blend obtained from step B to form the homogeneous gel.
In another embodiment, the process for preparing a pain relieving herbal topical gel composition comprising of boswellia gum extract, capsicum oleoresin, one or more other analgesic and anti-inflammatory agents and one or more pharmaceutically acceptable excipients wherein the process comprises of the following steps: A.
I. boswellia gum is mixed with isopropyl alcohol.
II. the mixture of step (I) is filtered through a suitable filter.
III. the filtrate obtained from step (II) is centrifuged to obtain a clear supernatant liquid.
IV. the clear supernatant liquid of boswellia gum extract obtained from step (III), capsicum oleoresin, methyl salicylate, menthol, clove oil and benzyl alcohol are mixed together to obtain the pre blend.
B.
I. water is heated and is mixed with glycerin, propylene glycol, carbomer, polysorbate, cresmer, linseed oil, seasame oil under constant homogenization to obtain a homogeneous mixture.
II. diethyl amine and/or triethanolamine is added to the homogeneous mixture obtained from step (I) under constant stirring to obtain a homogeneous blend.
C.
I. the pre-blend obtained from step A is mixed with the homogeneous blend obtained from step B to form the homogeneous gel.
The process for the preparation of a pain relieving herbal topical gel composition comprising boswellia gum extract, capsicum oleoresin, one or more other analgesic and anti-inflammatory agents and one or more pharmaceutically acceptable excipients is further illustrated by the following examples but should not be construed as limiting the scope of the invention.
Example 1

(Table removed)

*supernatant Quantity calculated on the basis of assay and overages included
Procedure
Step A
Boswellia gum was mixed with isopropyl alcohol and the mixture thus obtained was filtered
through a suitable filter. The filtrate thus obtained was centrifuged to obtain a clear supernatant
liquid. The clear supernatant liquid thus obtained was mixed with methyl salicylate, menthol,
capsicum oleoresin, clove oil and benzyl alcohol to obtain a pre-blend.
Step B
Water was heated and to the heated water linseed oil, glycerin, carbomer and tween were
added under constant homogenization to obtain a homogeneous mixture. Diethyl amine was
added to the homogeneous mixture under constant stirring to obtain a homogeneous blend.
Step C
The pre-blend of step A was mixed with the homogeneous blend of step B to obtain a
homogeneous gel.
Example 2
(Table removed)

*supernatant; * Quantity calculated on the basis of assay and overages included
Procedure
Step A
Boswellia gum was mixed with isopropyl alcohol and the mixture thus obtained was filtered
through a suitable filter. The filtrate thus obtained was centrifuged to obtain a clear supernatant
liquid. The clear supernatant liquid thus obtained was mixed with methyl salicylate, menthol,
capsicum oleoresin, clove oil and benzyl alcohol to obtain a pre-blend.
StepB
Water was heated and to the heated water linseed oil, glycerin, carbomer and cresmer were
added under constant homogenization to obtain a homogeneous mixture. Diethyl amine was
added to the homogeneous mixture under constant stirring to obtain a homogeneous blend.
StepC
The pre-blend of step A was mixed with the homogeneous blend of step B to obtain a
homogeneous gel.
Example 3
(Table removed)

*supematant; * Quantity calculated on the basis of assay and overages included
Procedure
Step A
Boswellia gum was mixed with isopropyl alcohol and the mixture thus obtained was filtered
through a suitable filter. The filtrate thus obtained was centrifuged to obtain a clear supernatant
liquid. The clear supernatant liquid thus obtained was mixed with methyl salicylate, menthol,
capsicum oleoresin, clove oil and benzyl alcohol to obtain a pre-blend.
Step B
Water was heated and to the heated water seasame oil, glycerin, carbomer and tween were
added under constant homogenization to obtain a homogeneous mixture. Diethyl amine was
added to the homogeneous mixture under constant stirring to obtain a homogeneous blend.
Step C
The pre-blend of step A was mixed with the homogeneous blend of step B to obtain a
homogeneous gel.
Example 4

(Table removed)

*supernatant;# Quantity calculated on the basis of assay and overages included
Procedure
Step A
Boswellia gum was mixed with isopropyl alcohol and the mixture thus obtained was filtered
through a suitable filter. The filtrate thus obtained was centrifuged to obtain a clear supernatant
liquid. The clear supernatant liquid thus obtained was mixed with methyl salicylate, menthol,
capsicum oleoresin, clove oil and benzyl alcohol to obtain a pre-blend.
Step B
Water was heated and to the heated water linseed oil, glycerin, propylene glycol, carbomer and
cresmer were added under constant homogenization to obtain a homogeneous mixture. Diethyl
amine was added to the homogeneous mixture under constant stirring to obtain a
homogeneous blend.
Step C
The pre-blend of step A was mixed with the homogeneous blend of step B to obtain a
homogeneous gel.
Example 5

(Table removed)

*supernatant; Quantity calculated on the basis of assay and overages included
Procedure
Step A
Boswellia gum was mixed with isopropyl alcohol and the mixture thus obtained was filtered
through a suitable filter. The filtrate thus obtained was centrifuged to obtain a clear supernatant
liquid. The clear supernatant liquid thus obtained was mixed with methyl salicylate, menthol,
capsicum oleoresin, clove oil and benzyl alcohol to obtain a pre-blend.
Step B
Water was heated and to the heated water linseed oil, glycerin, carbomer and tween were
added under constant homogenization to obtain a homogeneous mixture, triethanolamine was
added to the homogeneous mixture under constant stirring to obtain a homogeneous blend.
Step C
The pre-blend of step A was mixed with the homogeneous blend of step B to obtain a
homogeneous gel.

WE CLAIM:
1. A pain relieving herbal topical gel composition wherein the topical gel composition comprises of boswellia gum extract, capsicum oleoresin, one or more other analgesic and anti-inflammatory agent(s) and one or more pharmaceutically acceptable excipients.
2. The pain relieving herbal topical gel according to claim 1, wherein the amount of boswellia gum is from about 0.01% to 25% by weight.
3. The pain relieving herbal topical gel according to claim 1, wherein the amount of capsicum oleoresin is from about 0.001% to 10% by weight.
4. The pain relieving herbal topical gel according to claim 1, wherein other analgesic and anti-inflammatory agent(s) is selected from the group comprising of salicylate analgesics, rubefacients, counterirritants, herbal analgesics or anti-inflammatory agents and nonsteroidal anti-inflammatory agents as herein described.
5. The pain relieving herbal topical gel according to claim 3, wherein the effective amount of salicylate analgesics used is from about 0.1% to 30% by weight.
6. The pain relieving herbal topical gel according to claim 3, wherein the effective amount rubefacients used is from about 0.001% to 30% by weight.
7. The pain relieving herbal topical gel according to claim 3, wherein the effective amount of counterirritants used is from about 0.001% to 30% by weight.
8. The pain relieving herbal topical gel according to claim 1, wherein pharmaceutical^ acceptable excipients are selected from the group comprising of gel forming agents, humectants, skin permeation enhancers, neutralizing agents, surface-active agents, preservatives and solvents as herein described.
9. A process of preparing the pain relieving herbal topical gel according to claim 1, wherein the process comprises of the following steps:
A.
I. one or more of boswellia gum extract, capsicum oleoresin, other analgesic and antiinflammatory agents and optionally preservative(s) are mixed together to form a blend.
B.
I. a solvent is optionally heated and is mixed with one or more of pharmaceutically acceptable excipients selected from gel forming agents, humectants, skin permeation enhancers, surface-active agents, preservatives and solvents and one or more other analgesic and anti-inflammatory agents selected from the group comprising of salicylate analgesics, rubefacients, counterirritants, herbal analgesic or anti-inflammatory agents and non-steroidal anti-inflammatory agents under constant homogenization to form a homogeneous mixture.
II. a neutralizing agent is added to the homogeneous mixture of step (I) to form homogeneous blend.
I. the blend obtained from step A is mixed with homogeneous blend obtained from step B to form a homogeneous gel.
10. A pain relieving herbal topical gel composition wherein the topical gel composition as described and exemplified herein.