HERBAL NON-AQUEOUS GEL FOR RELIEVING PAIN AND INFLAMMATION
Technical Field of Invention
The present invention relates to a herbal non-aqueous gel for topical use for relieving pain and inflammation in a subject and method of preparation of the same. More particularly, the present invention relates to herbal non-aqueous gel comprising boswellia gum extract, capsicum oleoresin and other medicinal agents for relieving pain and inflammation in a subject and method of preparation of the same.
Background of the Invention
Pain is a complex perception which is variedly different among individuals who appear to have similar injuries or illnesses. It may range from an acute pain, which is caused by any inflammation or injury to tissues, to chronic pain, which represents disease itself and exists for a longer duration of time. The variety of situation which may lead to pain may include musculoskeletal disorder, sports activities leading to sprains and strains, improper body postures leading to back pain, muscle pain, joint pain etc., accidents, and various inflammatory and non-inflammatory diseases like rheumatoid arthritis, osteoarthritis and gout.
Inflammatory diseases like rheumatoid arthritis and gout affect millions of people worldwide. In general, arthritis means joint inflammation. The joint inflammation of rheumatoid arthritis causes swelling, pain, stiffness and redness in the joints. Gout, on the other hand, is a common form of arthritis in which uric acid crystals become deposited in the joint, causing an inflammatory reaction.
Herbal topical preparations, such as creams, lotions, liniments, ointments, aerosol sprays and gels containing analgesic and anti-inflammatory agents of herbal origin and/or non-steroidal anti-inflammatory agents for the treatment of inflammation and pain are well known in the art. US Patent no. 6949260 discloses a composition for treating inflammation and pain in humans with effective amount of boswellic acids, a curcuminoid, a gingirol, a capsaicinoid, a bioflavanoid and a vitamin C source. The compositions described herein are for oral administration. US Patent no. 3880996 discloses a topical analgesic ointment composition for the symptomatic relief of localized pain of musculo-skeletal etiology comprising an analgesic e.g. a salicylate, a rubefacient, and a organopolysiloxane. US Patent Application no. 2009098213 discloses a pain relief and soothing cream comprising an aqueous base, methyl salicylate, a skin stimulant comprising menthol and two or more reactants selected from the group of camphor, diclofenac, eucalyptus oil and ginger. US Patent no. 5178879 discloses a
clear, water soluble, non greasy gel consisting of capsaicin, carboxypolymethylene emulsifying agent, ethyl alcohol and water.
Herbal non-aqueous gel for topical application of analgesics and anti-inflammatory agents is a unique and first of its kind formulation in such a pain relieving category. The non-aqueous gel gets absorbed to the topical surfaces and body tissues upon application and provides protection and local delivery of analgesics and anti-inflammatory agents leading to much better local analgesia. The other major advantage of herbal non-aqueous gel is that unlike other formulations in this category which involves a heating process for dissolving the ingredients during the manufacturing operations, the process for the manufacture of non-aqueous gel involves no heating and the entire process is carried out at room temperature. Thus thermolabile and volatile ingredients can be easily incorporated in the non-aqueous gel formulation. Further, certain drugs or excipients which are sensitive to water and degradation can also be incorporated. Hence it would be advantageous to formulate herbal non-aqueous gel for topical application for relieving pain and inflammation in a subject.
The present invention relates to herbal non-aqueous gel for topical use for relieving pain and inflammation in a subject and method of preparation of the same. More particularly, the present invention relates to herbal non-aqueous gel comprising boswellia gum extract, capsicum oleoresin and other medicinal agents for relieving pain and inflammation in a subject and method of preparation of the same.
Summary of the Invention
In one general aspect, it relates to a herbal non-aqueous gel for topical administration for relieving pain and inflammation in a human subject wherein the non-aqueous gel comprises of boswellia gum extract, capsicum oleoresin, other medicinal agent(s) and one or more pharmaceutical carriers or excipients.
In another general aspect, it relates to a herbal non-aqueous gel for topical administration for relieving pain and inflammation in a human subject wherein the non-aqueous gel comprises of boswellia gum extract, capsicum oleoresin, other medicinal agent(s) and one or more pharmaceutical carriers or excipients wherein the other medicinal agents are selected from the group comprising of one or more rubefacient agents, one or more counterirritants and one or more analgesic and anti-inflammatory agents of herbal or non-herbal origin.
In another general aspect, it relates to a herbal non-aqueous gel for topical administration for relieving pain and inflammation in a human subject wherein the non-aqueous gel comprises of boswellia gum extract, capsicum oleoresin, other medicinal agent(s) and one or more pharmaceutical carriers or excipients are selected from the group comprising of gel-forming agents, humectants, skin permeation enhancers, preservatives and non-aqueous solvents.
In another general aspect, it relates to a herbal non-aqueous gel for topical administration for relieving pain and inflammation in a human subject wherein the non-aqueous gel comprises of boswellia gum extract, capsicum oleoresin, other medicinal agent(s) and one or more pharmaceutical carriers or excipients wherein the other medicinal agents are selected from the group comprising methyl salicylate, menthol and clove oil wherein one or more of pharmaceutical carriers or excipients are selected from the group comprising of isopropyl alcohol, benzyl alcohol, propylene glycol, glycerin, polyethylene glycol and carbomer.
In another general aspect, it relates to a process of preparing a herbal non-aqueous gel for topical administration for relieving pain and inflammation in a human subject wherein the nonaqueous gel comprises of boswellia gum extract, capsicum oleoresin, other medicinal agent(s) and pharmaceutical carriers or excipients wherein the process comprises of the following steps:
I. one or more of boswellia gum extract, capsicum oleoresin and/or other medicinal agents are mixed with one or more of pharmaceutical carriers or excipients selected from humectants, skin permeation enhancers, preservatives and non-aqueous solvents to form a blend.
II. one or more pharmaceutical carriers or excipients selected from gel forming agents are added in portions to the blend obtained from step (I) under constant homogenization till a homogeneous gel is obtained.
Detailed Description of the Invention
Gel is a semisolid system consisting of dispersion made up of either small inorganic particle or large organic molecules enclosed or interpenetrated by solvent. Gels consist of two phase system in which inorganic particles are not dissolved but merely dispersed throughout the continuous phase and large organic particles are dissolved in the continuous phase, randomly coiled in the flexible chains. Gels are classified based on the nature of solvent as aqueous gels and non-aqueous gels. Aqueous gels are water based whereas non-aqueous gels are based on organic solvents. Gels are most popular and widely used drug delivery system for topical administration.
The term "boswellia gum" as used herein refers to a gummy extract obtained from the gummy resins of the plants of genera Boswellia, Commiphora, and Bursera of the family Burseraceae.
This gummy resin is a complex mixture of various terpenoids, polysaccharides and inorganic salts. The terpenoids part constitutes both lower and higher terpenoids. The higher terpenoids portion is the pharmacologically active portion and is a complex mixture di and triterpenoids. Certain triterpenoids commonly known as boswellic acids are the active ingredients that give boswellia its analgesic and anti-inflammatory properties. Boswellic acids inhibit leukotriene synthesis by specifically inhibiting 5-lipoxygenase, the key enzyme of leukotriene biosynthesis. As used herein, the term "boswellic acids" includes all related acids such as p-boswellic acid, acetyl-p-boswellic acid, keto-p-boswellic acid, acetyl-keto-p-boswellic acid and any other related acids which provide the analgesic and anti-inflammatory effect of the boswellia gum extract. Based on the dose, the effective amount of boswellia gum 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 "extract" as used herein refers to solid or liquid concentrate resulting from an extraction process wherein the crude herbal material is contacted with an appropriate solvent to remove the substance(s) desired to be extracted from the material. Such an extraction can be carried out by any conventional process known in the art.
The term "capsicum oleoresin" as used herein refers to an oleoresin obtained from the dried fruits of the plant species capsicum frutesceens L of the family Solanaceae. The active ingredient of capsicum oleoresin is capsaicin. Capsaicin selectively binds to a protein known as TRPV1 that resides on the membranes of pain and heat sensing neurons and depletes presynaptic substance P, a neuropeptide involved in the transmission of pain impulses from the periphery to the central nervous system. Based on dose, the effective amount of capsicum oleoresin 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 medicinal agent(s) may be selected from the group comprising of rubefacient agents, counterirritants and analgesic and anti-inflammatory agents of herbal or non-herbal origin.
Rubefacient agents produce redness of skin by causing dilation of the capillaries and increase in the blood circulation to the irritated surface. Rubefacient agents may be selected from but are not limited to methyl salicylate, capsicum oleoresin, camphor, chloroform, menthol, allyl isothiocyanate and the like. Based on dose, the effective amount of rubefacient agents 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 produce an inflammatory reaction with the object of affecting another site usually adjacent to or underlying the irritated surface. Pain is only as intense as it is perceived, and the perception of other sensations from the application of the counterirritant, such as
massage and warmth, tend to crowd out perception of the pain. In addition, counterirritants may produce an increase in the flow of blood to the muscles which, with concomitant waste disposal and other chemical changes, enhances recovery. Counterirritants may be selected from but are not limiting to methyl salicylate, camphor, menthol, clove oil, eucalyptus oil, thymol and the like. Based on dose, the amount of counterirritants 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.
Analgesics and anti-inflammatory agents of herbal origin may include but are not limited to herbs or herbal extracts of the plants species Cinnamomum camphora, Trachyspermum ammi, Hyoscyamus niger, Commiphora wightii, Datura metel, Butea monosperma, Artemisia maritime, Mentha arvensis, Eugenia caryophyllata, Ocimum sanctum, Ocimum basilicum, Amorphophallus campanulatus, Berberis aristata, Vitex negundo, Carica papaya and the like. Analgesic and anti-inflammatory agents of non-herbal origin include but are not limited to nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, aspirin, diclofenac and the like.
One or more pharmaceutical carriers or excipients suitable for topical administration may be selected from gel-forming agents, humectants, skin permeation enhancers, preservatives and non-aqueous 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 mixtures thereof.
Suitable humectants may include but are not limiting to glycerin, sorbitol, propylene glycol, polyethylene glycol and mixtures 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 mixtures 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 mixtures thereof.
Suitable non-aqueous solvents may include but are not limited to ethanol, isopropyl alcohol, butyl alcohol, benzyl alcohol, dimethyl sulfoxide, dimethylformamide, N-methyl-2-pyrrolidone, pyrrolidone-2, 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 an herbal non-aqueous gel for topical administration for relieving pain and inflammation in a human subject wherein the non-aqueous gel comprises of boswellia gum extract, capsicum oleoresin, other medicinal agent(s) and pharmaceutical carriers or excipients suitable for topical administration wherein the process comprises of the following steps:
I. boswellia gum is mixed with non-aqueous 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 boswallia gum extract obtained from step (III), capsicum oleoresin, other medicinal agents and preservative(s) are mixed together to obtain the pre-blend.
V. the pre-blend obtained in step (IV) is mixed with humectant(s), skin permeation enhancer(s) and/or non-aqueous solvent(s) to obtain the final blend.
VI. gel forming agent(s) is added gradually to the final blend of step (V) in small portions under constant homogenization till a homogeneous gel is obtained.
In another embodiment, the process for preparing a non-aqueous gel for topical administration for relieving pain and inflammation in a human subject wherein the non-aqueous gel comprises of boswellia gum extract, capsicum oleoresin, other medicinal agent(s) and pharmaceutical carriers or excipients suitable for topical administration wherein the process comprises of the following steps:
I. boswellia gum is mixed with non-aqueous 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 medicinal agents are mixed together to obtain the pre-blend.
V. the pre-blend obtained in step (IV) is mixed with humectant(s), skin permeation enhancer(s), preservative(s) and/or non-aqueous solvent(s) to obtain the final blend.
VI. gel forming agent(s) is added gradually to the final blend of step (V) in small portions under constant homogenization till a homogeneous gel is obtained.
In another embodiment, the process for preparing a non-aqueous gel for topical administration for relieving pain and inflammation in a human subject wherein the non-aqueous gel comprises of boswellia gum extract, capsicum oleoresin, other medicinal agent(s) and pharmaceutical carriers or excipients suitable for topical administration wherein the process comprises of the following steps:
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.
V. the pre-blend obtained in step (IV) is mixed with propylene glycol, glycerin and/or polyethylene glycol to obtain the final blend.
VI. carbomer is added gradually to the final blend of step (V) in small portions under constant homogenization till a homogeneous gel is obtained.
The process for the preparation of an herbal non-aqueous gel comprising boswellia gum extract, capsicum oleoresin, other medicinal agent(s) and pharmaceutical carriers or excipients suitable for topical administration 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
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. The pre-blend was mixed with propylene glycol to obtain the final blend. The final blend was added with portions of carbomer under constant homogenization till a homogeneous gel was obtained.
Example 2

(Table removed)

*supernatant; ** Quantity calculated on the basis of assay and overages included
Procedure
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. The pre-blend was mixed with propylene glycol and glycerin to obtain the final blend. The final blend was added with portions of carbomer under constant homogenization till a homogeneous gel was obtained.
Example 3

(Table removed)

*supernatant; ** Quantity calculated on the basis of assay and overages included
Procedure
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. The pre-blend was mixed with propylene glycol, glycerin and polyethylene glycol to obtain the final blend. The final blend was added with portions of carbomer under constant homogenization till a homogeneous gel was obtained.
Example 4

(Table removed)

*supernatant; ** Quantity calculated on the basis of assay and overages included
Procedure
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. The pre-blend was mixed with polyethylene glycol to obtain the final blend. The final blend was added with portions of carbomer under constant homogenization till a homogeneous gel was obtained.

WE CLAIM:
1. A herbal non-aqueous gel for topical administration for relieving pain and inflammation in a human subject wherein the non-aqueous gel comprises of boswellia gum extract, capsicum oleoresin, other medicinal agent(s) and one or more pharmaceutical carriers or excipients.
2. The herbal non-aqueous gel according to claim 1, wherein the boswellia gum extract is from about 0.01% to 25% of boswellia gum.
3. The herbal non-aqueous gel according to claim 1, wherein the amount of capsicum oleoresin is from about 0.001% to 10% by weight.
4. The herbal non-aqueous gel according to claim 1, wherein the other medicinal agent(s) is selected from the group comprising of one or more rubefacient agents, counterirritants, analgesic and anti-inflammatory agents of herbal or non-herbal origin.
5. The herbal non-aqueous gel according to claim 4, wherein the amount of rubefacient agents is from about 0.001% to 30% by weight.
6. The herbal non-aqueous gel according to claim 4, wherein the amount of counterirritants is from about 0.001% to 30% by weight.
7. The herbal non-aqueous gel according to claim 4, wherein the other medicinal agent(s) is selected from one or more of methyl salicylate, menthol and clove oil.
8. The herbal non-aqueous gel according to claim 1, wherein one or more pharmaceutical carriers or excipients is selected from the group comprising of gel-forming agents, humectants, skin permeation enhancers, preservatives and non-aqueous solvents as herein described.
9. A process of preparing the herbal non-aqueous gel according to claim 1, wherein the process comprises of the following steps:

I. one or more of boswellia gum extract, capsicum oleoresin and/or other medicinal agents are mixed with one or more of pharmaceutical carriers or excipients selected from humectants, skin permeation enhancers, preservatives and non-aqueous solvents to form a blend.
II. one or more pharmaceutical carriers or excipients selected from gel forming agents are added in portions to the blend obtained from step (I) under constant homogenization till a homogeneous gel is obtained.
10. A herbal non-aqueous gel for topical administration for relieving pain and inflammation in a human subject substantially as described and exemplified herein.