DESC:Background
Neuropathic pain is a condition that is caused by a variety of different diseases, injuries and lesions that usually manifest as a series of symptoms and complications. Neuropathic pain is divided into two classes: central and peripheral neuropathic pain, depending on the site of the lesion that is causing the pain. Central neuropathic pain is triggered by spinal cord and/or brain damages or diseases, such as central post-stroke pain (CPSP) and neurodegenerative disorders, particularly Parkinson’s disease, and it affects the central somatosensory pathway. [D'Amico R et al., Int J Mol Sci. 2020 Jul 27;21(15):5330]. Peripheral neuropathy refers to conditions that involve damage to the peripheral nervous system, which is a vast communications network that sends signals between the central nervous system and all other parts of the body.
Pain is transmitted to the spinal cord by various receptors, like thermoreceptors, mechanoreceptors, chemoreceptors, and nociceptors which are capable of detecting noxious peripheral stimuli from joints, muscles, skin, and send these signals to the spinal cord and eventually to the brain for more processing. When a noxious stimulus activates an ion channel on a nociceptor and if the receptor potential is of sufficient magnitude to reach the voltage-gated channel activation threshold, then this will trigger potential action generation and pain transmission to the spinal cord.
Microglia are brain cells that regulate brain development, maintenance of neuronal networks, and injury repair. The role of microglia in neuropathic pain has been reported in several studies. [Colonna M et al., Annu Rev Immunol. 2017 Apr 26; 35:441-468]. Microglia plays an active part in preserving normal physiological conditions, as it perceives the cellular surroundings with its ramified processes and undergoes quick morphological changes in response to different stimuli including peripheral nerve injury (PNI). Similarly, mast cells also provide a potentially important peripheral immune signalling connection to the brain in the inflammatory setting. Mast cells are first responders to intervene as recruiters to initiate, amplify, and prolong all of the immune and nerve responses that arise from their activation. Studies demonstrate that the degranulation of mast cells can produce factors that sensitise nociceptors, thus directly contributing to neuropathic pain. The observations that mast cells and microglia are frequently involved at similar sites after nerve injury or inflammation has led to speculation as to whether both cell types may represent the chief actors in the regulation of inflammatory pain. Microglia and MC play an important role in mediating neuroinflammation astrocytes, oligodentrocytes, inflammasomes, cytokines, and chemokine. [Vallejo R Tilley DM Vogel L Benyamin R. The role of glia and the immune system in the development and maintenance of neuropathic pain. Pain Pract 2010;10(3):167–84]. Thus the regulation or modulation of the functions of mast cells and microglia will have beneficial effect on neuropathic pain.
Multiple recent studies have also reported the impact on the levels of intracellular/extracelluar molecules in the body during neuropsychotic pain. It has also been reported that during neuropathic pain “aliamides” are produced “on demand” by tissues, i.e., enzymatically released from membrane precursors when cells face potentially noxious stimuli, and they are principally metabolized by intracellular hydrolases [Esposito E. et al., Mini Rev. Med. Chem. 2013; 13:237–255]. Aliamides represent a small host of naturally occurring N-acyl ethanolamines (NAEs) that are particularly enriched in animal tissues. Levi-Montalcini was the first scientist to discover that the tissue accumulation of NAE occurred under pathological degenerative conditions, and this is an important biological response to control such inflammation [Aloe L., Leon A., Levi-Montalcini R., Inflamm. Res. 1993;39:C145–C147. doi: 10.1007/BF01972748]. The main mechanism of action of Aliamides mainly relies on the down-modulation of cell hyperactivity following injury. Their main cellular targets are mast cells (MCs), whose behaviour, proliferation, and function are under Aliamide control.
Thus the levels of Aliamides directly impact in the modulation of the mast cells. Aliamides represent a group of endogenous bioactive lipids, including palmitoyl ethanolamide (PEA), oleoyl ethanolamide (OEA), and stearoyl ethanolamide (SEA), which endogenous levels plays a central role in numerous biological processes, including pain, inflammation, and lipid metabolism.
It has also been reported that active nerve regeneration process also plays an important role in maintenance of neuropathic pain. Nerves carries signal to and from the brain throughout the body, and when a nerve is damaged, the signalling system is cut-off resulting in pain, numbness, burning or loss of function in affected areas. Peripheral Nerve injuries (PNIs) are estimated to occur in 2.8% of multiple trauma patients. Thus novel treatments to restore and augment nerve regeneration and accelerate functional recovery would greatly beneficial in the management and rehabilitation of nerve injuries and the resultant chronic pain. [Benga A et. al., Indian J Plast Surg. 2017 Jan-Apr;50(1):5-15. doi: 10.4103/ijps.IJPS_14_17. PMID: 28615804; PMCID: PMC5469235]
Thus the supplementation of agents that modulate or regulate the function of microglia and mast cells in combination with agents that aids in the repair and regeneration of damaged nerve cells will greatly benefit in reduction of neuropathic pain. The present invention provides a nutraceutical composition with combination of ingredients which supplements the endogenous lipids like Aliamides and ingredients that supplements the body requirement for the repairs and regeneration of nerve cells.
Objective
An objective of the present invention is to provide a composition for supplementing agents that aids in the recovery from neuropathic pain.
An objective of the present invention is to provide a composition for supplementing endogenous lipids that aids the recovery from neuropathic pain, wherein the endogenous lipids are N-(2-Hydroxyethyl)hexadecanamide, (9Z)-N-(2-Hydroxyethyl)octadec-9-enamide and N-(2-Hydroxyethyl)octadecanamide.
An objective of the present invention is to provide a composition for supplementing agents that aids in the recovery and regeneration of nerve cells, wherein the agents are Thiamine, Pyridoxine, Cobalamine and Niacin or combination thereof.
An objective of the present invention is to provide a nutraceutical composition as an adjunct to ongoing therapy for neuropathic pain, wherein the composition is composed of agents that modulates microglia and mast cells, and agents that aids in the recovery and regeneration of nerve cells.
An objective of the present invention is to provide a nutraceutical composition that supplements agents that helps in recovery from neuropathic pain, wherein the agents are not obtained through normal diet.
Summary
The present invention relates to a nutraceutical composition for the supplementation of agents that endogenously aids in the recovery of neuropathic pain, wherein the agents are combination of ingredients that modulates the activity of mast cells and microglia, and agents that aids in the recovery and regeneration of nerve cells.
The present invention also related to composition that comprises endogenous bioactive lipids, including N-(2-Hydroxyethyl)hexadecanamide, (9Z)-N-(2-Hydroxyethyl)octadec-9-enamide and N-(2-Hydroxyethyl)octadecanamide, which endogenous levels plays a central role in numerous biological processes, including pain, inflammation, and lipid metabolism.
The present invention also relates to composition that comprises ingredients that aids in the recovery and regeneration of nerve cells, wherein the agents are selected from Thiamine, Pyridoxine, Cobalamine and Niacin or a combination thereof.
Detailed Description
Definitions
The term “nutraceutical” as used herein refers to a food or food related component that intends for health benefits even in treatment and prevention of aliments
The term “dietary supplement” as used herein refers to ingredients that supplement the normal daily diet of a person.
In an embodiment the present invention provides a nutraceutical composition that supplements ingredients that aids in the recovery of neuropathic pain, wherein the ingredients are selected from agents that modulates the activity of microglia and mast cells, and ingredients that aids in the recovery and regeneration of nerve cells.
In an embodiment the present invention provides a nutraceutical composition that supplements the diet of individuals suffering from neuropathic pain, wherein the composition comprises of ingredients that are selected from agents that modulates the activity of microglia and mast cells, and ingredients that aids in the recovery and regeneration of nerve cells.
In an embodiment the present invention provides a nutraceutical composition that comprises of ingredients that modulates the activity of microglia and mast cells, wherein the ingredients are bioactive lipids and wherein the bioactive lipids are N-(2-Hydroxyethyl)hexadecanamide, (9Z)-N-(2-Hydroxyethyl)octadec-9-enamide and N-(2-Hydroxyethyl)octadecanamide, and wherein the endogenous levels of the lipids plays a central role in pain and inflammation.
In an embodiment the present invention provides a nutraceutical composition that comprises of ingredients that aids in the recovery and regeneration of nerve cells, wherein the ingredients are selected from Thiamine, Pyridoxine, Cobalamine and Niacin or a combination thereof.
In an embodiment the present invention provides a nutraceutical composition that comprises of a combination of ingredients, wherein the ingredients are
a) Agents that modulates the activity of microglia and mast cells
b) Agents that aids in the recovery and regeneration of nerve cells
Wherein, the agents that modulates the activity of microglia and mast cells are bioactive lipids and wherein the bioactive lipids are N-(2-Hydroxyethyl)hexadecanamide, (9Z)-N-(2-Hydroxyethyl)octadec-9-enamide and N-(2-Hydroxyethyl)octadecanamide, and the agents that aids in the recovery and regeneration of nerve cells are Thiamine, Pyridoxine, Cobalamine and Niacin or a combination thereof
In an embodiment the present invention provides a synergistic composition comprising a combination of ingredients that a) supplements the endogenously produced bioactive lipids which aids in the treatment of neuropathic pain, and b) aids in recovery and regeneration of nerve cells.
Wherein, the agents that supplements the endogenously produced bioactive lipids are N-(2-Hydroxyethyl)hexadecanamide, (9Z)-N-(2-Hydroxyethyl)octadec-9-enamide and N-(2-Hydroxyethyl)octadecanamide and the agent that aids in the recovery and regeneration of nerve cells are Thiamine, Pyridoxine, Cobalamine and Niacin or a combination thereof.
In an embodiment the present invention provides a dietary supplement for people suffering from neuropathic pain, wherein the dietary supplement acts as adjunct to the on-going therapy for neuropathic pain, wherein the on-going therapy includes administration of prescribed drugs.
In an another embodiment the dietary supplement is a solid unit dosage form which may be developed in form of tablets, capsules, powders, pellets, granules, microspheres, minitablets or any suitable solid unit forms known to person skilled in the art; mouth dissolving tablets; dispersible tablets; effervescent tablets; trilayer tablets; inlay tablets. In a preferred embodiment the preferred dosage form is tablet or capsule.
In an embodiment the composition further comprises of pharmaceutically acceptable excipients, wherein the excipients are selected from diluents, binders, disintegrants, lubricants, anti-adherants, coating agents, polymers, solvents, solubiliser, surfactants, flavorants, colarants and the likes thereof.
In an embodiment of the present invention, the agents that modulates the activity of microglia and mast cells are present in the amount of 100mg to 2000mg.
In an embodiment of the present invention, the agents that aids in the recovery and regeneration of nerve cells are present in the range of 0.1mg to 1000mg.
In an embodiment the present invention provides a nutraceutical composition comprises:
a) about 1200 mg N-(2-Hydroxyethyl)hexadecanamide and;
b) about 1.4 mg Thiamine and;
c) about 1.9 mg Pyridoxine and;
d) about 2.2 mg Cobalamine and;
e) about 11mg Niacin
In an embodiment the present invention provides a process to prepare the composition of the present invention.
Examples-
Example 1 – Capsule composition
S.NO. Active ingredients Amount
1 N-(2-Hydroxyethyl)hexadecanamide 1200mg
2 Thiamine 1.4mg
3 Pyridoxine 1.9mg
4 Cobalamine 2.2mg
5 Niacin 11mg
6 Pharmaceutically acceptable excipients As required
,CLAIMS:We claim:
1. A nutraceutical composition comprises a synergistic combination of ingredients that:
a. modulates the activity of microglia and mast cells and;
b. aids in recovery and regeneration of nerve cells
2. A nutraceutical composition as claimed in claim 1 wherein
a. bioactive lipids that modulates the activity of microglia and mast cells are N-(2-Hydroxyethyl)hexadecanamide, (9Z)-N-(2-Hydroxyethyl)octadec-9-enamide and N-(2-Hydroxyethyl)octadecanamide and
b. the agent that aids in the recovery and regeneration of nerve cells are Thiamine, Pyridoxine, Cobalamine and Niacin or a combination thereof.
3. A nutraceutical composition as claimed in claim 2 wherein bioactive lipids are present in the amount of 100mg to 2000mg.
4. A nutraceutical composition as claimed in claim 2 that aids in the recovery and regeneration of nerve cells are present in the range of 0.1mg to 1000mg.
5. A nutraceutical composition as claimed in claim 1-4 provides a nutraceutical composition comprises:
a) about 1200 mg N-(2-Hydroxyethyl)hexadecanamide and;
b) about 1.4 mg Thiamine and;
c) about 1.9 mg Pyridoxine and;
d) about 2.2 mg Cobalamine and;
e) about 11mg Niacin and;
6. A nutraceutical composition as claimed in claim 1-5 is present in form of tablets, capsules, powders, pellets, granules, microspheres and minitablets.
7. A nutraceutical composition as claimed in claim 6 is a capsule comprising:
a. about 1200 mg N-(2-Hydroxyethyl)hexadecanamide and;
b. about 1.4 mg Thiamine and;
c. about 1.9 mg Pyridoxine and;
d. about 2.2 mg Cobalamine and;
e. about 11mg Niacin and;
8. A nutraceutical composition as claimed in claim 1-5 further comprises pharmaceutically acceptable excipients, wherein the excipients are selected from diluents, binders, disintegrants, lubricants, anti-adherants, coating agents, polymers, solvents, solubiliser, surfactants, flavorants, colarants and combinations thereof.