BG2867U1 - Composition of a means for assisting the regeneration of the periferal nerves - Google Patents

Abstract

The present utility relates to a stable and effective acting composition comprising uridine monophosphate, vitamin B1 (thiamine), vitamin B3 (nicotinamide), vitamin B6 (pyridoxine), vitamin B12 (cyanocobalamin) and folic acid in combination which assists regenerating of peripheral nerves while simultaneously provides uridine monophosphate, folic acid and vitamins whose deficiency in the human body leads to unwanted symptomatology and the likelihood of pathological manifestations. According to preferred variations of the utility model, the amount of uridine monophosphate is 50 mg. The amount of Vitamin B1 is preferably 4 mg. The amount of Vitamin B3 is preferably 10 mg. The amount of Vitamin B6 is preferably 6 mg. The amount of Vitamin B12 is preferably 10 ?g. The amount of folic acid is preferably 400 ?g. The composition, according to the utility model, as containing as active ingredients the combination of uridine monophosphate, folic acid and vitamins B1, B3, B6, B12, is found that it assist the regeneration of peripheral nerves as an increase of nucleic acid and protein synthesis in the neuron and stimulation of the formation of a myelin sheath is achieved.

Description

Field of technology

The utility model refers to a means of aiding in the regeneration of the peripheral nerves of a subject in need thereof.

BACKGROUND OF THE INVENTION

The pathological changes in peripheral neuropathies are nonspecific, with macrophages being detected that phagocytose myelin and axonal debris. Advanced axonal neuropathy shows loss of myelinated axons and increased endoneural collagen, and some chronic demyelinating neuropathies show hypertrophic changes.

Myelin is an elongated and modified plasma membrane of schwannocytes wrapped in a spiral around the axon of the peripheral nerve. Myelin acts as an insulator that accelerates the conduction of the nerve signal and its disruption leads to pathological changes and manifestations.

Patent document JP 2010155861 is known, which discloses the use of a pyrimidine nucleotide to stimulate the regeneration of the peripheral nervous system. The composition according to JP 2010155861 includes uridine 5'-monophosphoric acid or cytidine alone as a pharmaceutically active ingredient.

Therefore, there is a need to provide means that combine and effectively support the regeneration of peripheral nerves in order to avoid the occurrence of pathological changes, especially in subjects in need.

Technical essence of the utility model

The present utility model provides a peripheral nerve regeneration aid composition that contains uridine monophosphate, vitamin B1 (thiamine), vitamin B3 (nicotinamide), vitamin B6 (pyridoxine), vitamin B12 (cyanocobalamin) and folic acid as active ingredients.

The inventors of the present utility model found an unexpectedly good efficiency in the regeneration of peripheral nerves of uridine monophosphate, vitamin B1 (thiamine), vitamin B3 (nicotinamide), vitamin B6 (pyridoxine), vitamin B12 (cyanocobalamin) and folic acid in combination with one of the components did not deactivate the others and in addition the combined composition showed stability meeting the standards in the field.

In order to understand the essence of the present utility model, it is important to indicate the role of each of the active components included in the composition on the peripheral neurons. In this regard, we state that: Uridine monophosphate is a nucleotide of formula:

which is important for the synthesis of ribonucleic acids (RNA) and other biologically active compounds. It is absorbed from the intestinal tract by facilitated diffusion using specific uridine transporters.

Descriptions to certificates for registration of utility models № 03.1 / 15.03.2018

The role of uridine monophosphate in neurons is associated with the fact that it:

• Participates in the synthesis of RNA • Participates in the synthesis of phosphatidylcholine, and hence in the construction of cell membranes • Builds dendrites that support synaptic function • Stimulates cell proliferation of schwannocytes and hence the construction of myelin • Induces cell growth and differentiation two mechanisms: by direct interaction with its P2Y2 receptor and by activating the NGF signaling pathway and its TrkA receptor. Thus, it exerts a neuroprotective effect. • Interacts with the nucleotide receptors of schwannocytes and activates the molecular apparatus, which induces changes in the cytoskeleton of the altered glial cells in neuropathies.

It is important to note that some pharmacological studies indicate that uridine accelerates and promotes neuromuscular regeneration and inhibits the conduction of spinal cord pain.

Folic acid has the formula:

Folic acid, also called Vitamin B9, is one of the most important vitamins for health. Its role on neurons is linked to the fact that a large number of its derivatives with similar biological activity, called folate, are involved in a number of enzymes. It is involved in the synthesis of amino acids, and hence protein molecules. Participates in the synthesis of nucleotides and plays a key role in the synthesis of DNA and RNA, which determine cell division. It affects the activity of genes in nerve cells and helps regulate genes involved in regeneration. Parenterally administered folic acid or its derivatives are known to result in 10-fold dose-dependent axonal regeneration and functional recovery from trauma in adults.

Vitamin B12 or cobalamin has the structural formula:

R = 5-deoxyadenosyl, methyl, OH, CN

The role of vitamin B12 on neurons is associated with the fact that it is required for the production of myelin. It plays a key role in two important human biochemical reactions:

• The first is the formation of methionine by methylation of homocysteine. A by-product of this reaction is the formation of tetrahydrofolate, which is an important precursor in the synthesis of purines and

Descriptions to certificates for registration of utility models № 03.1 / 15.03.2018 pyramids, and hence of RNA and DNA.

• The second important reaction is the conversion of L-methylmalonyl coenzyme A to succinyl coenzyme A, which is essential for the formation of the myelin sheath.

Stiffness, tingling and loss of sensation in the limbs are the visible symptoms of peripheral neuropathy due to Vitamin B12 deficiency. Statistics show that between 5% and 20% of the adult population is deficient in Vitamin B12, and up to 40% have low plasma levels of Vitamin B12.

Vitamin B6 has a structural formula

Its role on neurons is related to the fact that after absorption Vitamin B6 or pyridoxine is converted into pyridoxal phosphate, which is an important cofactor in many metabolic reactions of amino acids, glucose and lipids.

In adults, Vitamin B6 deficiency neuropathy begins with tingling, paraesthesia, or burning pain in the feet, which then rises and affects the legs and arms. Neurological examination showed polyneuropathy with decreased distal sensitivity, decreased tendon reflexes, ataxia, and mild distal weakness.

Although vitamin B6 is present in many foods, their processing leads to a loss of vitamin up to 70%. On the other hand, humans are not able to synthesize B6, so diet is essential.

Vitamin B1 or also known as thiamine has a structural formula

Vitamin B1 is a water-soluble vitamin and is present in most plant and animal tissues. Thiamine is absorbed in the small intestine by passive diffusion and active transport and is rapidly converted to thiamine diphosphate (TDP), which is the physiologically active form. TDP serves as a major co-factor in oxidative processes (cellular respiration), ATP production, glutamate and γ-aminobutyric acid synthesis, and myelin sheath maintenance. Thiamine deficiency leads to a neuropathy known as Berry-Berry and is the first human failure syndrome described.

Fatigue, irritability and muscle cramps can occur within days to weeks as a result of a nutritional deficiency. The clinical picture of thiamine deficiency begins with distal sensory loss, burning pain, paraesthesia, or muscle weakness in the legs and feet.

Vitamin B3 or also known as niacin or nicotinic acid has a structural formula

Descriptions to certificates for registration of utility models № 03.1 / 15.03.2018

Vitamin B3 is an indispensable vitamin for humans. It is absorbed in the intestine by simple diffusion. Niacin and its derivatives are important for the metabolism of carbohydrates, fats and proteins, as well as for the transmission of intercellular signals and DNA repair.

Niacin deficiency in food can cause nausea, skin and lip lesions, anemia, headache and fatigue. Pellagra is a clinical manifestation of VZ deficiency, whose classic clinical triad is dementia, dermatitis and diarrhea.

Thus, the inventors of the present utility model have created a stable and effective composition containing uridine monophosphate, vitamin B1 (thiamine), vitamin B3 (nicotinamide), Vitamin B6 (pyridoxine), vitamin B12 (cyanocobalamin) and folic acid in combination, which helps regeneration of peripheral nerves while providing uridine monophosphate, folic acid and vitamins, the deficiency of which in the human body leads to unwanted symptoms and the likelihood of pathological manifestations.

The composition according to the present utility model in a preferred embodiment contains one or more of the active ingredients in the following quantitative ranges:

- Uridine, which is in the form of uridine or in the form of uridine mono-, di- or triphosphate): from 0 to 1000 mg

- Folic acid (in the form of folic acid or a salt of folic acid, ie folate): from 0 to 1000 pg

- Vitamin B1 (in the form of thiamine or benfotiamine): from 0 to 100 mg

- Vitamin B3 (as niacin or nicotinamide): 0 to 300 mg

- Vitamin B6 (in the form of any pyridoxine salt): 0 to 400 mg

- Vitamin B12 (as cyanocobalamin or methylcobalamin): 0 to 500 pg

According to one embodiment of the utility model, the uridine is uridine monophosphate and is preferably 50 mg.

According to another embodiment of the utility model, the amount of Vitamin B1 is preferably in an amount of 4 mg.

According to another embodiment of the utility model, the amount of Vitamin B3 is preferably 10 mg.

According to another embodiment of the utility model, the amount of Vitamin B6 is preferably 6 mg.

According to another embodiment of the utility model, the amount of Vitamin B12 is preferably 10 pg.

According to a further embodiment of the utility model, the amount of folic acid is preferably 400 pg.

In addition, the composition according to the utility model may optionally include one or more of the following components: Vitamin A, Beta-carotene, Vitamin D, Vitamin E, Vitamin K, Vitamin B1, Vitamin B2 (riboflavin), nicotinic acid), nicotinamide , pantothenic acid, Vitamin B6, folic acid, Vitamin B12, Biotin, Vitamin C calcium, magnesium, iron copper, iodine, zinc, manganese, selenium, chromium (trivalent), molybdenum, phosphorus.

Example implementation of the utility model

To understand the technical nature of the utility model, an exemplary embodiment of the peripheral nerve regeneration support composition is presented below, which example should not be construed as limiting the scope of the utility model as defined in the claims.

Descriptions to certificates for registration of utility models № 03.1 / 15.03.2018

Active components Content in one capsule of 520 mg ± 5%. (mg) Content compared to the recommended daily intake (%) Uridine monophosphate 50 mg Vitamin Bi (thiamine) 4 mg 364% Vitamin B ₃ (nicotinamide) 10 mg 63% Vitamin B ₆ (pyridoxine) 6 mg 429% Vitamin B1 ₂ (cyanocobalamin) 10 pg 400% Folic acid 400 pg 200% Excipients maltodextrin (sealant) 240 mg microcrystalline cellulose (sealant) 100 mg magnesium stearate (anti-caking agents) 9.59 mg

In addition, the composition according to the utility model in one embodiment optionally includes one or more of the following components: Vitamin A, beta-carotene, Vitamin D, Vitamin E, Vitamin K, Vitamin B2 (riboflavin), pantothenic acid, Biotin, Vitamin C calcium , magnesium, iron, copper, iodine, zinc, manganese, selenium, chromium (trivalent), molybdenum, phosphorus, the weight amount being determined by the total capsule capacity, which in this case is 520 mg ± 5%.

The mixture of active ingredients is prepared using a technique known in the art for dry mixing the components in a suitable mixer under suitable manufacturing conditions known to those skilled in the art. It is necessary to control the humidity and dusting in the premises. As excipients, it is possible to add means to ensure the free flow of the powder mixture of active ingredients before mixing with the excipients and filling into, for example, gelatin capsules. Such excipients may be anti-caking agents. As excipients it is possible to include in combination a flavor masking agents, sweeteners, sweeteners and the like known in the art and readily available from the literature references in the art.

Clinical data on the effect of the combination of uridine monophosphate according to the present utility model

It has been established during the development of the present utility model that the combination of uridine monophosphate, folic acid and vitamin B12 has a positive effect on the clinical manifestation of peripheral neuropathies. The intensity of neuropathic pain responded successfully and decreased significantly (p <0.001), and nonsteroidal anti-inflammatory drugs were reduced or discontinued in 77.4% of patients.

The combination of uridine monophosphate, folic acid and vitamin B12 in patients with symptomatic neuropathies as a result of compression leads to a decrease in the overall score for pain, intensity

100 Descriptions to certificates for registration of utility models № 03.1 / 15.03.2018 of the pain, the nature of the pain and the accompanying symptoms.

Clinical monitoring performed with the combination of uridine monophosphate, folic acid and Vitamins B1, B3, B6, B12 in 29 patients with peripheral neuropathies followed for two months showed clinical data on antinociceptive effect and effect on axonal regeneration and remyelination in peripheral neuropathies and specific neuropathies. back pain.

The advantages of the composition containing as active components the combination of uridine monophosphate, folic acid and Vitamins B1, B3, B6, B12 according to the utility model are associated with the fact that it supports the regeneration of peripheral nerves by:

• Increase the synthesis of nucleic acids and proteins in the neuron • Stimulate the formation of myelin sheath.

Claims (8)

Claims A composition of a peripheral nerve regeneration aid comprising excipients and characterized in that it contains as active ingredients one or more of uridine, Vitamin B1, Vitamin B3, Vitamin B6, Vitamin B12 and folic acid, and one or more more than the following additional components: Vitamin A, beta-carotene, Vitamin D, Vitamin E, Vitamin K, Vitamin B1, Vitamin B2 (riboflavin), nicotinic acid, nicotinamide, pangothenic acid, Biotin, Vitamin C, calcium, magnesium, iron, copper, iodine, zinc, manganese, selenium, chromium - trivalent, molybdenum, phosphorus. Composition according to Claim 1, characterized in that the uridine is in the form of uridine or uridine mono-, di- or triphosphate and is present in an amount of up to 1000 mg; filiic acid is in the form of folic acid or folate and is present in an amount up to 1000 pg; Vitamin B1 is in the form of thiamine or benfotiamine and is in an amount of up to 100 mg, Vitamin B3 is in the form of niacin or nicotinamide and is in an amount of up to 300 mg; Vitamin B6 is a salt of pyridoxine and is in an amount of up to 400 mg; Vitamin B12 is in the form of cyanocobalamin or methylcobalamin and is up to 500 pg. Composition according to Claim 2, characterized in that the uridine monophosphate is in an amount of 50 mg. Composition according to Claim 1 or 2, characterized in that Vitamin B1 is in an amount of 4 mg. Composition according to any one of the preceding claims, characterized in that Vitamin B3 is in an amount of 10 mg. Composition according to any one of the preceding claims, characterized in that Vitamin B6 is in an amount of 6 mg. Composition according to any one of the preceding claims, characterized in that Vitamin B12 is in an amount of 10 pg. Composition according to any one of the preceding claims, characterized in that the folic acid is present in an amount of 400 pg.