WO2013108262A1 - Synergistic combination for the treatment of diabetic neuropathy - Google Patents
Synergistic combination for the treatment of diabetic neuropathy Download PDFInfo
- Publication number
- WO2013108262A1 WO2013108262A1 PCT/IN2012/000044 IN2012000044W WO2013108262A1 WO 2013108262 A1 WO2013108262 A1 WO 2013108262A1 IN 2012000044 W IN2012000044 W IN 2012000044W WO 2013108262 A1 WO2013108262 A1 WO 2013108262A1
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- WIPO (PCT)
- Prior art keywords
- diabetic
- treatment
- loss
- neurotharapy
- methylcobalamin
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7135—Compounds containing heavy metals
- A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
Definitions
- FIELD OF INVENTION This invention is based on synergistic treatment of Diabetic neuropathy by three active ingredients which are taurine, folic acid and Methylcobalamin.
- the invention relates to a new paradigm of disease centering around the metabolic pathways of S- adenosyl-L-methionine (SAM), the intermediates of these pathways and other metabolic pathways influenced by the SAM pathways.
- SAM S- adenosyl-L-methionine
- the invention relates to analyzing and regulating SAM pathways that exist in association with a disease or condition including cancer and a number of diseases or conditions connected with degeneration and aging. More specifically, the invention concerns designing analytical, diagnostic and therapeutic protocols and agents for such disease states and conditions through recognition of the central role of SAM and its metabolic pathways in controlling cell metabolism, cell growth and intercellular communication.
- Skin care products according to the present invention comprise partially hydrolyzed fiicoidan and a base.
- the invention proposes the sure of reduced glutathione in a liposome (liposomal 'reduced glutathione) for the oral administration of a therapeutically effective amount to ameliorate the progression of vascular disease, including atherosclerosis, diabetes, hypertension, narrowing of arteries leading to decreased blood flow, ischemic events, and the formation of blood clots, abnormal platelet aggregation, and thrombotic events, by reducing the amount and effect of oxidized cholesterol, oxidized HDL and oxidized LDL.
- the invention also proposes combining liposomal encapsulated glutathione with statin drugs to improve the effect of lowering not only cholesterol but also the oxidized cholesterol as well as oxidized HDL and oxidized LDL.
- the invention also proposes combining liposomal encapsulated glutathione with CoQIO as a therapy for vascular disease and management of side effects of statin therapy
- An ingestible nerve and circulatory nutritional formulation comprising an antioxidant portion, an anti-inflammatory portion, a circulatory enhancement portion, a vasodilator portion, a nerve growth, conduction and regeneration portion, a glycemic control portion, a sorbitol inhibitor portion a lipid reduction portion, a mitochondrial activation portion and a pancreatic stem cell support element portion
- the cobalt-sulphur bond may be provided directly by administration of a thiolatocobalamin, such as glutathionyl-cobalamin or indirectly by the co-administration of Vitamin B 12 (or a derivative thereof) with a sulphur-containing molecule, such as glutathione or a precursor thereof.
- a thiolatocobalamin such as glutathionyl-cobalamin
- Vitamin B 12 or a derivative thereof
- a sulphur-containing molecule such as glutathione or a precursor thereof.
- the cobalt-sulphur bond may be provided directly by administration of a thiolatocobalamin, such as glutathionyl-cobalamin or indirectly by the co-administration of Vitamin B 12 (or a derivative thereof) with a sulphur- containing molecule, such as glutathione or a precursor thereof.
- a thiolatocobalamin such as glutathionyl-cobalamin
- Vitamin B 12 or a derivative thereof
- a sulphur- containing molecule such as glutathione or a precursor thereof.
- the present invention relates to methods and compositions for treating glaucoma, and more particularly to methods and compositions for reducing one or more non- intraocular pressure- dependent risk factors of glaucoma through neuroprotection.
- the present invention is a method and composition for reversing dysfunction of the human autonomic nervous system.
- the invention consists of administering a methylation-prompting composition that promotes uninterrupted recycling of homocysteine to methionine and uninterrupted processing and removal of metabolic products of stress.
- a dietary supplement of mitochondrial nutrients is designed for relieving stress, preventing and improving stress-related disorders, such as chronic fatigue syndrome, diabetes, age-associated cognitive dysfunction and diseases (Parkinson's and Alzheimer's disease).
- the supplement composition has the following nutrients: B vitamins (cyanocobalamin 2-1,000 ug, thiamin 1- 1,000 mg, niacin 15-2,000 mg, pyridoxine 1-1,000 mg, Pantothenate 5-150 mg, folic acid 400-40,000 ug), alpha-tocopherol 10-800 mg, ascorbic acid 50-10,000 mg, calcium 20-2,000 mg, vitamin A 200-10,000 ug, alpha-lipoic acid 100-1,000 mg, N-acetyl cysteine 100-3,000 mg, L-carnosine 100-9,000 mg, tyrosine 100-9,000 mg, vanillin 10-100 mg, phosphatidylserine 10-800 mg, resveratrol 10-50 mg, dehydroepiandrosterone 1-50 mg, and melatonin 0.1-3 mg, all of which have been individually used experimentally or clinically for relieving stress, preventing and treating age- and stress-related disorders and diseases but no combination of these compounds has been used. Many embodiments also contain at least one adjunct ingredient such
- the present invention relates to a nutritional supplement composition and methods for preparing.
- the invention further provides a method for creating a nutrient supplement drink composition comprising the a carrier liquid, a flower distillate, and at least one herbal extract component, and optionally including an additional ingredient selected from the group consisting of a second herbal extract component, a nutrient, a flavoring agent, a preservative, a coloring agent, a second carrier agent, and combinations thereof.
- An ingestible nerve and circulatory nutritional formulation comprising an antioxidant portion, an antiinflammatory portion, a circulatory enhancement portion, a vasodilator portion, a nerve growth, conduction and regeneration portion, a glycemic control portion, a sorbitol inhibitor portion a lipid reduction portion, a mitochondrial activation portion and a pancreatic stem cell support element portion.
- the object of the invention is that it's an oral treatment of Diabetic neuropathy * This is safe and efficient.
- neuropathic pain Many medications are available for the treatment of diabetic neuropathic pain. These include tricyclic antidepressants, gabapentin, pregabalin, duloxetine, topical lidocaine, and capsaicin. Other medications such as carbamazepine, oxcarbazepine, phenytoin, lamotrigine, and opioids may also be used. Topical therapy with capsaicin or lidocaine patches may be useful in some patients, especially those with more localized pain or those in whom interactions with existing oral medications is a concern.
- Diabetic neuropathy is neuropathic disorders that are associated with mellitus. These are compounds are useful for the treatment of Diabetic neuropathy
- Diabetic neuropathy is neuropathic disorders that are associated with diabetes mellitus. These conditions are thought to result from diabetic microvascular injury involving small blood vessels that supply nerves (vasa nervorum).Diabetic neuropathy includes third nerve palsy. Mononeuropathy; mononeuropathy multiplex; diabetic amyotrophic; a painful polyneuropathy; autonomic neuropathy; and thoracoabdominal neuropathy.
- Diabetic neuropathy affects all peripheral nerves: pain fibers, motor neurons, autonomic nerves. It therefore necessarily can affect all organs and systems since all are innervated. There are several distinct syndromes based on the organ systems and members affected, but these are by no means exclusive. A patient can have sensorimotor and autonomic neuropathy or any other combination.
- Symptoms vary depending on the nerve affected and may include symptoms other than those listed. Symptoms usually develop gradually over years. Treatment of diabetic neuropathy using combined administration of a formulation including as an active ingredient, antioxidant with an anti-diabetic agent in order to improve nerve conduction velocities. Suitable anti- diabetic agents.
- Symptoms may include:
- Peripheral nerves are sensitive conduits that carry impulses from the extremities back to the central nervous system (i.e., the spinal cord and brain). Impulses are transmitted along nerves by changes in the electrical charge of the cell membrane caused by movement of ions such as sodium, potassium, and calcium. Impulses are transmitted between nerves by neurotransmitters such as acetylcholine and substance P, which is responsible for transmitting pain impulses.
- neurotransmitters such as acetylcholine and substance P, which is responsible for transmitting pain impulses.
- myelin a thin sheath
- the myelin functions like the rubber wrapping around an electrical cord: it insulates the nerve fibers and prevents abnormal transmissions.
- diabetic neuropathy for example, there is a change in the microvascular network that supplies the nerve with nutrients. This lack of blood supply and nutrients causes the nerve to function abnormally. Diabetic neuropathy tends to occur in more than one nerve area (this condition is called polyneuropathy) and may cause loss of sensation and pain that typically worsens at night. In severe cases, diabetics can suffer from a kind of neuropathy called autonomic neuropathy. In this case, the autonomic nervous system, which controls automatic body functions, is affected with possibly serious consequences, including gastrointestinal problems, bladder-emptying problems, abnormal heart rhythms, and even sudden death.
- the autonomic nervous system is composed of nerves serving the heart, gastrointestinal system and genitourinary system.
- Autonomic neuropathy can affect any of these organ systems.
- the most commonly recognized autonomic dysfunction in diabetics is orthostatic hypotension, or fainting when standing up.
- diabetic autonomic neuropathy it is due to the failure of the heart and arteries to appropriately adjust heart rate and vascular tone to keep blood continually and fully flowing to the brain. This symptom is usually accompanied by a loss of the usual change in heart rate seen with normal breathing.
- GI tract manifestations include gastroparesis, nausea, bloating, and diarrhea. Because many diabetics take oral medication for their diabetes, absorption of these medicines is greatly > affected by the delayed gastric emptying. This can lead to hypoglycemia when an oral diabetic agent is taken before a meal and does not get absorbed until hours, or sometimes days later, when there is normal or low blood sugar already. Sluggish movement of the small intestine can cause bacterial overgrowth, made worse by the presence of hyperglycemia. This leads to bloating, gas and diarrhea.
- Urinary symptoms include urinary frequency, urgency, incontinence and retention. Again, because of the retention of urine, urinary tract infections are frequent. Urinary retention can lead to bladder diverticulitis, stones, reflux nephropathy.
- oculomotor When cranial nerves are affected, oculomotor (3rd) neuropathies are most common.
- the oculomotor nerve controls all of the muscles that move the eye with the exception of the lateral rectus and superior oblique muscles. It also serves to constrict the pupil and open the eyelid.
- the onset of diabetic third nerve palsy is usually abrupt, beginning with frontal or periorbital pain and then diplopia. All of the oculomotor muscles innervated by the third nerve may be affected, but those that control pupil size are usually well-preserved early on.
- the parasympathetic nerve fibers within CNIII that influence pupillary size are found on the periphery of the nerve (in 3 ⁇ 4rms of a cross sectional view), which makes them less susceptible to ischemic damage (as they are closer to the vascular supply).
- the sixth nerve, the abducens nerve, which innervates the lateral rectus muscle pf the eye (moves the eye laterally), is also commonly affected but fourth nerve, the trochlear nerve, (innervates the superior oblique muscle, which moves the eye downward) involvement is unusual.
- Mononeuropathies of the thoracic or lumbar spinal nerves can occur and lead to painful syndromes that mimic myocardial infarction, cholecystitis or appendicitis. Diabetics have a higher incidence of entrapment neuropathies, such as carpal tunnel syndrome.
- Diabetic peripheral neuropathy is the most likely diagnosis for someone with diabetes who has pain in a leg or foot, although it may also be caused by vitamin B12 deficiency or osteoarthritis
- Diabetic neuropathy by the combination of following three compounds like taurine, folic acid and Methylcobalamin.
- concentrations of these compounds are Methylcobalamin is 1500 microgram per tablet, taurine is 500 mg and folic acid is 5 mg per tablet.
- This combination can relief in the infections on the feet and legs, in multiple fractures of the knee, ankle or foot, and develop a Charcot joint, as well as loss of motor function results in dorsiflexion, contractures of the toes, loss of the interosseous muscle function and leads to contraction of the digits, so called hammer toes , the loss of the musculature makes the hand appear gaunt and skeletal and the loss of muscular function.
- Methylcobalamin is a cobalamin (MeCbl or MeB12) used in the treatment of peripheral neuropathy, diabetic neuropathy, and as a preliminary treatment for Amyotrophic lateral sclerosis. It is a form of vitamin B12 and differs from cyanocobalamin in that the cyanide is replaced by a methyl group.
- the liver converts a small amount of cyanocobalamin into methylcobalamin within the body, but larger amounts of methylcobalamin are necessary to correct neurological defects and protect against aging.
- supplemental B 12 The most common forms of supplemental B 12 are cyanocobalamin or hydroxycobalamin.
- the natural form of B12 found in food is methylcobalamin (or a similar form, adenosylcobalamin).
- the structure of B12 is very complex, with numerous methyl groups attached. Methyl groups (CH3) are used in beneficial methylation reactions, such as those that reduce homocysteine.
- Methylcobalamin appears to be the most effective form of vitamin B 12 to protect the nerves.
- Folic acid also known as vitamin B9 or folacin
- folate the naturally occurring form
- pteroyl-L-glutamic acid and pteroyl-L-glutamate are forms of the water-soluble vitamin B9.
- Folic acid is itself not biologically active, but its biological importance is due to tetrahydrofolate and other derivatives after its conversion to dihydrofolic acid in the liver.
- Type 1 diabetes mellitus patients have lower plasma levels of folic acid and may benefit from folic acid supplements or folic acid fortified food products.
- Taurine or 2-aminoethanesulfonic acid, is an organic acid. It is a major constituent of bile and can be found in the lower intestine and, in small amounts, in the tissues of many animals, including humans. Taurine is a derivative of the sulfur-containing (sulfhydryl) amino acid cysteine. Taurine is one of the few known naturally occurring sulfonic acids.
- Taurine produces anxiolytic effect and may act as a modulator or anti-anxiety agent in the central nervous system. Taurine can influence (and possibly reverse) defects in nerve blood flow, motor nerve conduction velocity, and nerve sensory thresholds in experimental diabetic neuropathic rats. Taurine is regularly used as an ingredient in energy drinks. Taurine may exert a beneficial effect in preventing diabetes-associated microangiopathy and tubulointerstitial injury in diabetic nephropathy. Taurine acts as a glycation inhibitor.
Abstract
This invention is based on an efficient treatment of diabetic neurotherapy. The drug combination is made up three ingredients. These are taurine, folic acid and methylcobalamin. These are working as a synergistic compound for the treatment of diabetic neurotherapy the concentration of these compounds are Methylcobalamin is 1500 microgram per tablet, taurine is 500 mg per tablet and folic acid is 5 mg per tablet. In this combination taurine is used for anxiolytic effect and may act as a modulator or anti- anxiety agent in the central nervous system. Folic acid is used for the mechanism of blood glucose control. It is essential because glucose causes high levels of oxidative stress throughout the body. In antioxidant therapy folic acid is very important antioxidant to help prevent neuropathy and Methylcobalamin is used in the treatment of diabetic neuropathy, it is a form of vitamin B12. Methylcobalamin are necessary to correct neurological defects. This combination can provide relief in infections on the feet and legs, in multiple fractures of the knee, ankle or foot, a Charcot joint as well as loss of motor function resulting in dorsiflexion, contractures of the toes, loss of the interosseous muscle function and contraction of the digits, so called hammer toes, loss of the musculature making the hand appear gaunt and skeletal and the loss of muscular function.
Description
SYNERGISTIC COMBINATION FOR THE TREATMENT OF DIABETIC NEUROPATHY
FIELD OF INVENTION: This invention is based on synergistic treatment of Diabetic neuropathy by three active ingredients which are taurine, folic acid and Methylcobalamin.
PRIOR ART:
In the existing system as given in WO 1996/033703 A2 (patent application)/AU 721067 B2 (granted patent)/US 6020139 (granted patent) US 6596701 (granted patent) wherein The invention relates to a new paradigm of disease centering around the metabolic pathways of S- adenosyl-L-methionine (SAM), the intermediates of these pathways and other metabolic pathways influenced by the SAM pathways. Specifically, the invention relates to analyzing and regulating SAM pathways that exist in association with a disease or condition including cancer and a number of diseases or conditions connected with degeneration and aging. More specifically, the invention concerns designing analytical, diagnostic and therapeutic protocols and agents for such disease states and conditions through recognition of the central role of SAM and its metabolic pathways in controlling cell metabolism, cell growth and intercellular communication.
In the existing system as given in WO 2007/140022 A2 (patent application)/AU 2007/267823 Al (patent application)/US 2008/0089941 Al (patent application) wherein Compositions and methods relating to partially hydrolyzed fiicoidan for use in dietary supplements and skin- care products are described. Fucoidan from brown seaweeds is partially hydrolyzed and or sulfonated and then mixed with other ingredients for use as a dietary supplement in beverage, capsule, or tablet form or for use as a skin-care product. Other ingredients that can be included in the dietary supplements include vitamins, minerals, amino acids, carotenoids, flavonoids, antioxidants, aminosugars, glycosaminogrycans, and botanicals. Skin care products according to the present invention comprise partially hydrolyzed fiicoidan and a base.
In the existing system as given in WO 2007/053810 A2 (patent application)wherein The invention proposes the sure of reduced glutathione in a liposome (liposomal 'reduced glutathione) for the oral administration of a therapeutically effective amount to ameliorate the progression of vascular disease, including atherosclerosis, diabetes, hypertension, narrowing of arteries leading to decreased blood flow, ischemic events, and the formation of blood clots, abnormal platelet aggregation, and thrombotic events, by reducing the amount and effect of oxidized cholesterol, oxidized HDL and oxidized LDL. The invention also proposes combining liposomal encapsulated glutathione with statin drugs to improve the effect of lowering not only cholesterol but also the oxidized cholesterol as well as oxidized HDL and oxidized LDL. The invention also proposes combining liposomal encapsulated glutathione with CoQIO as a therapy for vascular disease and management of side effects of statin therapy
In the existing system as given in WO 2003/028747 Al (patent application)/US 2003/0068391 Al (patent application) wherein An ingestible nerve and circulatory nutritional formulation is disclosed, comprising an antioxidant portion, an anti-inflammatory portion, a circulatory enhancement portion, a vasodilator portion, a nerve growth, conduction and regeneration portion, a glycemic control portion, a sorbitol inhibitor portion a lipid reduction portion, a mitochondrial activation portion and a pancreatic stem cell support element portion
In the existing system as given in EP 1381373 Bl (granted patent) wherein A method and medical composition for the treatment and/or prevention of a functional Vitamin B12 deficiency in an individual that is brought about as a consequence of oxidative stress on biochemical pathways. The functional Vitamin B12 deficiency may eventually present as dementia, other neuropsychiatric abnormality and/or vascular disease. The method involves the administration of a medical composition that supplies a cobalt-sulphur bond in the upper β-ligand of an intracellular cobalamin molecule thereby facilitating intracellular processing of cobalamin. The cobalt-sulphur bond may be provided directly by administration of a thiolatocobalamin, such as glutathionyl-cobalamin or indirectly by the co-administration of Vitamin B 12 (or a derivative thereof) with a sulphur-containing molecule, such as glutathione or a precursor thereof.
In the existing system as given in WO 2002/087593 A I (patent application)/AU 2002/251315 Al (patent application)/US 7709460 (granted patent)/US 2004/0157783 Al (patent
application) wherein A method and medical composition for the treatment and/or prevention of a functional Vitamin B12 deficiency in an individual that is brought about as a consequence of oxidative stress on biochemical pathways. The functional Vitamin B12 deficiency may eventually present as dementia, other neuropsychiatric abnormality and/or vascular disease. The method involves the administration of a medical composition that supplies a cobalt-sulphur bond in the upper β-ligand of an intracellular cobalamin molecule thereby facilitating intracellular processing of cobalamin. The cobalt-sulphur bond may be provided directly by administration of a thiolatocobalamin, such as glutathionyl-cobalamin or indirectly by the co-administration of Vitamin B 12 (or a derivative thereof) with a sulphur- containing molecule, such as glutathione or a precursor thereof.
In the existing system as given in WO 2006/121421 A2 (patent application) wherein The present invention relates to methods and compositions for treating glaucoma, and more particularly to methods and compositions for reducing one or more non- intraocular pressure- dependent risk factors of glaucoma through neuroprotection.
In the existing system as given in US 2008/0045448 Al (patent application) wherein The present invention is a method and composition for reversing dysfunction of the human autonomic nervous system. The invention consists of administering a methylation-prompting composition that promotes uninterrupted recycling of homocysteine to methionine and uninterrupted processing and removal of metabolic products of stress.
In the existing system as given in US 2006/0257502 Al (patent application) wherein A dietary supplement of mitochondrial nutrients is designed for relieving stress, preventing and improving stress-related disorders, such as chronic fatigue syndrome, diabetes, age-associated cognitive dysfunction and diseases (Parkinson's and Alzheimer's disease). The supplement composition has the following nutrients: B vitamins (cyanocobalamin 2-1,000 ug, thiamin 1- 1,000 mg, niacin 15-2,000 mg, pyridoxine 1-1,000 mg, Pantothenate 5-150 mg, folic acid 400-40,000 ug), alpha-tocopherol 10-800 mg, ascorbic acid 50-10,000 mg, calcium 20-2,000 mg, vitamin A 200-10,000 ug, alpha-lipoic acid 100-1,000 mg, N-acetyl cysteine 100-3,000 mg, L-carnosine 100-9,000 mg, tyrosine 100-9,000 mg, vanillin 10-100 mg, phosphatidylserine 10-800 mg, resveratrol 10-50 mg, dehydroepiandrosterone 1-50 mg, and melatonin 0.1-3 mg, all of which have been individually used experimentally or clinically for relieving stress, preventing and treating age- and stress-related disorders and diseases but no
combination of these compounds has been used. Many embodiments also contain at least one adjunct ingredient such as coenzyme Q 10-200 mg, acetyl-L-carnitine 100-2,000 mg, choline 50-1,000 mg, and creatine 100-2,000 mg.
In the existing system as given in US 2008/0038367 Al (patent application) wherein The present invention relates to a nutritional supplement composition and methods for preparing. The invention further provides a method for creating a nutrient supplement drink composition comprising the a carrier liquid, a flower distillate, and at least one herbal extract component, and optionally including an additional ingredient selected from the group consisting of a second herbal extract component, a nutrient, a flavoring agent, a preservative, a coloring agent, a second carrier agent, and combinations thereof.
In the existing system as given in (WO/2003/028747) wherein An ingestible nerve and circulatory nutritional formulation is disclosed, comprising an antioxidant portion, an antiinflammatory portion, a circulatory enhancement portion, a vasodilator portion, a nerve growth, conduction and regeneration portion, a glycemic control portion, a sorbitol inhibitor portion a lipid reduction portion, a mitochondrial activation portion and a pancreatic stem cell support element portion.
OBJECT OF THE INVENTION
The object of the invention is that it's an oral treatment of Diabetic neuropathy* This is safe and efficient.
Many medications are available for the treatment of diabetic neuropathic pain. These include tricyclic antidepressants, gabapentin, pregabalin, duloxetine, topical lidocaine, and capsaicin. Other medications such as carbamazepine, oxcarbazepine, phenytoin, lamotrigine, and opioids may also be used. Topical therapy with capsaicin or lidocaine patches may be useful in some patients, especially those with more localized pain or those in whom interactions with existing oral medications is a concern. Any of these medications may be associated with
side effects, and patients should be counselled about possible problems before initiating treatment But these active combinations are used in the infections on the feet and legs, in multiple fractures of the knee, ankle or foot, and develop a Charcot joint, as well as loss of motor function results in dorsiflexion, contractures of the toes, loss of the interosseous muscle function and leads to contraction of the digits, so called hammer toes , the loss of the musculature makes the hand appear gaunt and skeletal and the loss of muscular function.
STATEMENT OF INVENTION
This invention is based on an efficient treatment of Diabetic neuropathy. Diabetic neuropathy is neuropathic disorders that are associated with mellitus. These are compounds are useful for the treatment of Diabetic neuropathy
DETAILED DESCRIPTION AND SCOPE OF THE INVENTION:
This invention is based on an efficient treatment of Diabetic neuropathy. Diabetic neuropathy is neuropathic disorders that are associated with diabetes mellitus. These conditions are thought to result from diabetic microvascular injury involving small blood vessels that supply nerves (vasa nervorum).Diabetic neuropathy includes third nerve palsy. Mononeuropathy; mononeuropathy multiplex; diabetic amyotrophic; a painful polyneuropathy; autonomic neuropathy; and thoracoabdominal neuropathy.
Diabetic neuropathy affects all peripheral nerves: pain fibers, motor neurons, autonomic nerves. It therefore necessarily can affect all organs and systems since all are innervated. There are several distinct syndromes based on the organ systems and members affected, but these are by no means exclusive. A patient can have sensorimotor and autonomic neuropathy or any other combination.
Symptoms vary depending on the nerve affected and may include symptoms other than those listed. Symptoms usually develop gradually over years.
Treatment of diabetic neuropathy using combined administration of a formulation including as an active ingredient, antioxidant with an anti-diabetic agent in order to improve nerve conduction velocities. Suitable anti- diabetic agents.
Symptoms may include:
Numbness and tingling of extremities
Dysesthesia (decreased or loss of sensation to a body part)
Diarrhea
Erectile dysfunction
Urinary incontinence (loss of bladder control) Impotence
Facial, mouth and eyelid drooping
Vision changes
Dizziness
Muscle weakness
Difficulty swallowing
Speech impairment
Fasciculation (muscle contractions)
Anorgasmia
Burning or electric pain
Some reasons for neuropathy
In all forms of neuropathy, there is abnormal stimulation of nerves or damage that results in pain. Peripheral nerves are sensitive conduits that carry impulses from the extremities back to the central nervous system (i.e., the spinal cord and brain). Impulses are transmitted along nerves by changes in the electrical charge of the cell membrane caused by movement of ions such as sodium, potassium, and calcium. Impulses are transmitted between nerves by neurotransmitters such as acetylcholine and substance P, which is responsible for transmitting pain impulses. For protection, most nerves are covered with a thin sheath called myelin, which is made from choline and lipids. The myelin functions like the rubber wrapping around an electrical cord: it insulates the nerve fibers and prevents abnormal transmissions.
In diabetic neuropathy, for example, there is a change in the microvascular network that supplies the nerve with nutrients. This lack of blood supply and nutrients causes the nerve to function abnormally. Diabetic neuropathy tends to occur in more than one nerve area (this condition is called polyneuropathy) and may cause loss of sensation and pain that typically worsens at night. In severe cases, diabetics can suffer from a kind of neuropathy called autonomic neuropathy. In this case, the autonomic nervous system, which controls automatic body functions, is affected with possibly serious consequences, including gastrointestinal problems, bladder-emptying problems, abnormal heart rhythms, and even sudden death.
Effects on nerve types
Different nerves are affected in different ways Sensorimotor poly neuropathy
Longer nerve fibers are affected to a greater degree than shorter ones, because nerve conduction velocity is slowed in proportion to a nerve's length. In this syndrome, decreased sensation and loss of reflexes occurs first in the toes on each foot, and then extends upward. It is usually described as glove-stocking distribution of numbness, sensory loss, dysesthesia and night time pain. The pain can feel like burning, pricking sensation, achy or dull. Pins and needles sensation is common. Loss of proprioception, the sense of where a limb is in space, is affected early. These patients cannot feel when they are stepping on a foreign body, like a splinter, or when they are developing a callous from an ill-fitting shoe. Consequently, they are at risk for developing ulcers and infections on the feet and legs, which can lead to
amputation. Similarly, these patients can get multiple fractures of the knee,- ankle or foot, and develop a Charcot joint. Loss of motor function results in dorsiflexion, contractures of the toes, loss of the interosseous muscle function and leads to contraction of the digits, so called hammer toes. These contractures occur not only in the foot but also in the hand where the loss of the musculature makes the hand appear gaunt and skeletal. The loss of muscular function is progressive.
Autonomic neuropathy
The autonomic nervous system is composed of nerves serving the heart, gastrointestinal system and genitourinary system. Autonomic neuropathy can affect any of these organ systems. The most commonly recognized autonomic dysfunction in diabetics is orthostatic hypotension, or fainting when standing up. In the case of diabetic autonomic neuropathy, it is due to the failure of the heart and arteries to appropriately adjust heart rate and vascular tone to keep blood continually and fully flowing to the brain. This symptom is usually accompanied by a loss of the usual change in heart rate seen with normal breathing. These two findings suggest autonomic neuropathy.
GI tract manifestations include gastroparesis, nausea, bloating, and diarrhea. Because many diabetics take oral medication for their diabetes, absorption of these medicines is greatly > affected by the delayed gastric emptying. This can lead to hypoglycemia when an oral diabetic agent is taken before a meal and does not get absorbed until hours, or sometimes days later, when there is normal or low blood sugar already. Sluggish movement of the small intestine can cause bacterial overgrowth, made worse by the presence of hyperglycemia. This leads to bloating, gas and diarrhea.
Urinary symptoms include urinary frequency, urgency, incontinence and retention. Again, because of the retention of urine, urinary tract infections are frequent. Urinary retention can lead to bladder diverticulitis, stones, reflux nephropathy.
Cranial neuropathy
When cranial nerves are affected, oculomotor (3rd) neuropathies are most common. The oculomotor nerve controls all of the muscles that move the eye with the exception of the lateral rectus and superior oblique muscles. It also serves to constrict the pupil and open the
eyelid. The onset of diabetic third nerve palsy is usually abrupt, beginning with frontal or periorbital pain and then diplopia. All of the oculomotor muscles innervated by the third nerve may be affected, but those that control pupil size are usually well-preserved early on. This is because the parasympathetic nerve fibers within CNIII that influence pupillary size are found on the periphery of the nerve (in ¾rms of a cross sectional view), which makes them less susceptible to ischemic damage (as they are closer to the vascular supply). The sixth nerve, the abducens nerve, which innervates the lateral rectus muscle pf the eye (moves the eye laterally), is also commonly affected but fourth nerve, the trochlear nerve, (innervates the superior oblique muscle, which moves the eye downward) involvement is unusual. Mononeuropathies of the thoracic or lumbar spinal nerves can occur and lead to painful syndromes that mimic myocardial infarction, cholecystitis or appendicitis. Diabetics have a higher incidence of entrapment neuropathies, such as carpal tunnel syndrome.
Diagnosis
Diabetic peripheral neuropathy is the most likely diagnosis for someone with diabetes who has pain in a leg or foot, although it may also be caused by vitamin B12 deficiency or osteoarthritis
The treatment of Diabetic neuropathy by the combination of following three compounds like taurine, folic acid and Methylcobalamin. The concentrations of these compounds are Methylcobalamin is 1500 microgram per tablet, taurine is 500 mg and folic acid is 5 mg per tablet.
This combination can relief in the infections on the feet and legs, in multiple fractures of the knee, ankle or foot, and develop a Charcot joint, as well as loss of motor function results in dorsiflexion, contractures of the toes, loss of the interosseous muscle function and leads to contraction of the digits, so called hammer toes , the loss of the musculature makes the hand appear gaunt and skeletal and the loss of muscular function.
Methylcobalamin
Methylcobalamin is a cobalamin (MeCbl or MeB12) used in the treatment of peripheral neuropathy, diabetic neuropathy, and as a preliminary treatment for Amyotrophic lateral
sclerosis. It is a form of vitamin B12 and differs from cyanocobalamin in that the cyanide is replaced by a methyl group.
The liver converts a small amount of cyanocobalamin into methylcobalamin within the body, but larger amounts of methylcobalamin are necessary to correct neurological defects and protect against aging.
Role of Methylcobalamin
The most common forms of supplemental B 12 are cyanocobalamin or hydroxycobalamin. The natural form of B12 found in food is methylcobalamin (or a similar form, adenosylcobalamin). The structure of B12 is very complex, with numerous methyl groups attached. Methyl groups (CH3) are used in beneficial methylation reactions, such as those that reduce homocysteine. Methylcobalamin appears to be the most effective form of vitamin B 12 to protect the nerves.
Folic acid
Folic acid (also known as vitamin B9 or folacin) and folate (the naturally occurring form), as well as pteroyl-L-glutamic acid and pteroyl-L-glutamate, are forms of the water-soluble vitamin B9. Folic acid is itself not biologically active, but its biological importance is due to tetrahydrofolate and other derivatives after its conversion to dihydrofolic acid in the liver.
Type 1 diabetes mellitus patients have lower plasma levels of folic acid and may benefit from folic acid supplements or folic acid fortified food products.
Permanent nerve damage could theoretically occur if vitamin B12 deficiency is not treated. Therefore, intake of supplemental folic acid should not exceed 1000 micrograms (1000 = 1 mg) per day to prevent folic acid from masking symptoms of vitamin B 12 deficiency.
Role of folic acid
In diabetic neuropathy, blood glucose control is essentia] because glucose causes high levels of oxidative stress throughout the body. In antioxidant therapy folic acid is very important antioxidant to help prevent neuropathy.
Taurine
Taurine, or 2-aminoethanesulfonic acid, is an organic acid. It is a major constituent of bile and can be found in the lower intestine and, in small amounts, in the tissues of many animals, including humans. Taurine is a derivative of the sulfur-containing (sulfhydryl) amino acid cysteine. Taurine is one of the few known naturally occurring sulfonic acids.
Role of taurine
Taurine produces anxiolytic effect and may act as a modulator or anti-anxiety agent in the central nervous system. Taurine can influence (and possibly reverse) defects in nerve blood flow, motor nerve conduction velocity, and nerve sensory thresholds in experimental diabetic neuropathic rats. Taurine is regularly used as an ingredient in energy drinks. Taurine may exert a beneficial effect in preventing diabetes-associated microangiopathy and tubulointerstitial injury in diabetic nephropathy. Taurine acts as a glycation inhibitor.
Treatment of diabetic neuropathy using combined administration of a formulation including as an active ingredient, antioxidant with an anti-diabetic agent in order to improve nerve conduction velocities.
Claims
(1) A Synergistic combination for the treatment of diabetic neurotharapy.
(2) Treatment of diabetic neurotharapy are comprises of taurine, folic acid and Methylcobalamin.
(3) Treatment of diabetic neurotharapy as recited in Claim 2 wherein Methylcobalamin is used as a form of vitamin B12.it is necessary to correct neurological defects.
(4) Treatment of diabetic neurotharapy as recited in Claim 3 wherein the concentration of methylcobalamin is 1500 microgram per tablet.
(5) Treatment of diabetic neurotharapy as recited in Claim 2 wherein taurine is used for anxiolytic effect and may act as a modulator or anti-anxiety agent in the central nervous system.
(6) Treatment of diabetic neurotharapy as recited in Claim S wherein the concentration of taurine is 500 mg per tablet.
(7) Treatment of diabetic neurotharapy as recited in Claim 2 wherein folic acid is used for the mechanism of blood glucose control. It is essential because glucose causes high levels of oxidative stress throughout the body.
(8) Treatment of diabetic neurotharapy as recited in Claim 7 wherein the concentration of folic acid is 5 mg per tablet.
(9) Treatment of diabetic neurotharapy as recited in Claim 2 wherein this combination can relief in the infections on the feet and legs, in multiple fractures of the knee, ankle or foot, and develop a Charcot joint, as well as loss of motor function results in dorsiflexion, contractures of the toes, loss of the interosseous muscle function and leads to contraction of the digits, so called hammer toes , the loss of the musculature makes the hand appear gaunt and skeletal and the loss of muscular function
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YAQUB B A ET AL: "Effects of methylcobalamin on diabetic neuropathy", CLINICAL NEUROLOGY AND NEUROSURGERY, ELSEVIER, AMSTERDAM, NL, vol. 94, no. 2, 1 July 1992 (1992-07-01), pages 105 - 108,109, XP024364756, ISSN: 0303-8467, [retrieved on 19920701], DOI: 10.1016/0303-8467(92)90066-C * |
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