RU2761617C2 - Complex of myelin lipids of central and peripheral nervous system of animals for treatment and prevention of neurodegenerative demyelinating disorders and methods for its application - Google Patents

Abstract

FIELD: pharmaceutics.

SUBSTANCE: group of inventions relates to the pharmaceutical industry, namely to the use of a complex of animal myelin lipids for the preparation of a drug for the treatment or prevention of neurodegenerative demyelinating damage to nervous tissue, to a pharmaceutical composition, as well as to a method for the treatment or prevention of neurodegenerative demyelinating damage to nervous tissue. Application of a complex of animal myelin lipids is proposed, including lipid metabolites, cholesterol, phospholipids, growth and differentiation factors of nervous tissue, essential fatty acids, obtained by drying tissues of the central or peripheral nervous system of animals in frozen form under vacuum, adding 70 % ethyl alcohol in the amount of 10 % by volume, followed by extraction by supercritical CO₂ extraction at a pressure of 680-800 bar and a temperature of 80°C for the preparation of a drug for the treatment or prevention of neurodegenerative demyelinating damage to nervous tissue. A pharmaceutical composition for the treatment or prevention of neurodegenerative demyelinating damage to nervous tissue contains therapeutically effective amount of a complex of animal myelin lipids and a pharmaceutically acceptable carrier containing a fat base. A method for the treatment or prevention of acute neurodegenerative demyelinating damage to the nervous tissue in a patient is also proposed.

EFFECT: above-described group makes it possible to effectively treat and prevent acute neurodegenerative demyelinating damage to the nervous tissue in the patient, without undesirable side reactions and restrictions in use.

23 cl, 5 ex

Description

TECHNICAL FIELD OF THE INVENTION

The present invention relates to medicine, in particular to neurology, and discloses an agent for the treatment or prevention of neurodegenerative demyelinating processes of the central and peripheral nervous systems, which is a complex of myelin lipids of the nervous tissue of animals, consisting of lipid metabolites, cholesterol, phospholipids, growth and differentiation factors, essential fatty acids. Disclosed are a pharmaceutical composition and a method of using the claimed composition for the treatment and prevention of neurodegenerative demyelinating processes. The claimed complex can be used orally for the treatment and prevention of multiple sclerosis (pathology of the central nervous system (CNS)), Guillain-Barré syndrome, leprosy neuropathy (pathology of the peripheral nervous system (GHS)). In addition, the complex can be used for diseases such as various types of sclerosis and other neurodegenerative disorders associated with "demyelination", the general consequence of which is the loss of lipids in the sheath of neuronal axons with impaired conduction of electrical signals.

LEVEL OF TECHNOLOGY

To date, there is no effective pathogenetically substantiated method of treatment and prevention of neurodystrophic demyelinating diseases. The currently used drugs in the course of treatment do not eliminate the cause of these diseases and have many unfavorable side effects, as a result of which these diseases acquire a long chronic course, and a significant part of patients develop disability.

Thus, modern therapeutic agents for the treatment of demyelinating conditions (interferon, glatiramer acetate, fingolimod) are only partially effective. The usefulness of long-term treatment courses is uncertain and is reported to be often accompanied by fatal side effects. For example, this applies to monoclonal antibodies such as Tysabri.

Modern chemotherapy and immunosuppressive therapy are characterized by the use of cytotoxic agents or immunosuppressants. Despite their effectiveness, these drugs are nonspecific and, especially in the case of long courses, toxic to normal and rapidly dividing cells. Moreover, their use can be limited by their inherent disadvantageous properties, including acute myelosuppression, nephrotoxicity, cardiotoxicity, neurotoxicity, toxic effects on the gastrointestinal tract, bladder and lungs, which can lead to a deterioration in the patient's condition for a long time.

The stimulating role of lipids in the regenerative processes of the nervous tissue is known. In living organisms, lipids perform energy and structural functions: in fat cells, the body's energy supply is preserved, and in tissues, lipids are the main component of cell membranes. Nervous tissue is characterized by a high content of lipids involved in the functioning of cell membranes, which are not synthesized by the body, and their need is provided by the diet. The development of nerve cells is genetically programmed; therefore, nerve cells need to ensure an adequate supply of lipids during their proliferation and differentiation.

Myelin is a fatty layer that surrounds the axons of many neurons and is formed by a series of spiral folds in the plasma membrane of glial cells (Schwann cells). Myelin membrane lipids play an important role as targets in the development of neurodegenerative and regenerative processes. It is especially important to provide cells with lipids in neurodegenerative conditions when the need for them increases for regeneration, especially myelin. The chemical heterogeneity of both lipid and protein composition of myelin suggests that oligodendrocytes (glia) and Schwann cells in different parts of the central and peripheral nervous system are able to form various molecular types of myelin, differing not only in molecular architectonics, but also in functional and immunochemical properties. This is also confirmed by pathological (demyelinating) processes characteristic only for the central nervous system or only for the peripheral nervous system. So, in multiple sclerosis, the body's immune system attacks the nerves of the central nervous system, destroying the myelin of the brain and spinal cord, while in Guillain-Barré syndrome and leprosy neuropathy, the immune attack is directed at the myelin (Schwann cells) sheath of peripheral nerves without affecting the brain. Therefore, when developing pathogenetically grounded therapeutic agents for the nervous system, it is necessary to take into account the specificity of the target tissue.

Demyelinating neurodystrophic processes affect many components of myelin: phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylglycerol, phosphatidylserine, phosphatidic acid, sphingomyelin, sulfatide, cerebrosides, ceramide and lysophosphatidylchol. For example, the target for autoantibodies in multiple sclerosis is the phosphate group on phosphatidylserine and oxidized derivatives of phosphatidylcholine. It was found that oral administration of these lipids alleviates experimental autoimmune encephalomyelitis by suppressing the activation and inducing apoptosis of autoreactive T cells. Consequently, the intake of a complex of lipids with food, which are similar in characteristics to the myelin lipids of the cells of the central or peripheral nervous systems, is a pathogenetically substantiated effect on the processes of regeneration of nerve tissues. The structural features of myelin and the clinical diversity of demyelinating processes in the central and peripheral nervous systems determine the choice of the active components of the composition. Thus, the claimed pharmaceutical composition for the treatment of demyelinating conditions of the central nervous system (for example, multiple sclerosis) contains a lipid complex of myelin of the central nervous system (spinal cord) of animals. At the same time, for the treatment of demyelinating conditions of the peripheral nervous system (for example, Guillain-Barré syndrome, leprosy neuropathy), a lipid complex of myelin of the peripheral nervous system is included in the pharmaceutical composition.

There is no information in the literature on the presence of therapeutic and / or prophylactic properties in the lipid complex of myelin of the central and peripheral nervous systems of animals.

Without intending to be limited by any theory, the inventors believe that the claimed composition suppresses the activity of autoreactive T and B cells, the inflammation caused by them and satisfies the increased need of the body for lipids during the regeneration of nerve tissues.

Known stimulating role of polyunsaturated fatty acids - PUFA, namely omega-3 and / or omega-6 fatty acids in combination with uridine or choline salts in relation to increasing the synthesis of synaptic proteins in synaptic membranes by a nerve cell with age-related memory disorder (RU 2436571). Polyunsaturated fatty acids have been proposed to be used to delay the onset of dementia or reduce its severity (RU 2444356). WO 2012/131493 discloses compositions containing long chain polyunsaturated fatty acids (PUFAs), other omega-3 PUFAs, and monounsaturated fatty acids. These compositions are intended for the treatment of neurological disorders. RU 2513995 describes the use of derivatives of polyunsaturated fatty acids, in particular 2-hydroxy derivatives, for the treatment, inter alia, of neurological or neurodegenerative disorders. RU 2507742 discloses the use of compositions containing long-chain polyunsaturated fatty acids, nitrogen monoxide releasing compounds, and medium-chain triglycerides to enhance cognitive function, reduce or prevent a decrease in social behavior, reduce or prevent age-related changes in behavior, improve learning ability, and maintain optimal function. brain, facilitate learning and memorization, reduce memory loss, slow down the aging of the brain, prevent or treat strokes, and prevent or treat dementia. Thus, the qualitative composition of the above agents is limited mainly by polyunsaturated fatty acids, which reduces the medicinal value and, accordingly, limits the breadth of application of these agents. At the same time, the pharmacological activity of PUFA compounds is low.

In view of the above, there is a need in the art for the development of new effective basic therapeutic agents that do not have the drawbacks of currently used drugs, in particular, do not cause undesirable side effects and do not have restrictions in use.

DISCLOSURE OF THE INVENTION

The problem solved by the invention is to create a new pathogenetically substantiated agent for the treatment and prevention of neurodegenerative demyelinating conditions of the central and peripheral nervous system, devoid of unwanted side effects and restrictions in use.

In its first aspect, the proposed invention relates to an agent for the treatment or prevention of neurodegenerative demyelinating lesions of nervous tissue, which is a complex of animal myelin lipids containing lipid metabolites, cholesterol, phospholipids, growth factors and differentiation of nervous tissue, essential fatty acids. However, in one preferred embodiment, the animal myelin lipid complex is derived from the central nervous system. In another preferred embodiment, the animal myelin lipid complex is derived from the peripheral nervous system.

The claimed agent has the ability to suppress the demyelinating inflammatory response and, being a source of lipid metabolites, stimulates the process of regeneration of the myelin sheath of cells.

In a further aspect, the claimed invention relates to a pharmaceutical composition for the treatment or prevention of neurodegenerative demyelinating lesions of nervous tissue, comprising a therapeutically effective amount of an animal myelin lipid complex comprising lipid metabolites, cholesterol, phospholipids, nerve tissue growth and differentiation factors, essential fatty acids, and a pharmaceutically acceptable carrier.

In one preferred embodiment of the pharmaceutical composition, the myelin lipid complex is derived from the central nervous system of animals. In another preferred embodiment of the pharmaceutical composition, the myelin lipid complex is derived from the peripheral nervous system of animals.

In a further preferred embodiment of the pharmaceutical composition, the pharmaceutically acceptable carrier comprises a fat base. In a more preferred embodiment, the fat base comprises rendered fat tail.

In another preferred embodiment, the pharmaceutical composition comprises:

a) a complex of myelin lipids of the central nervous system of animals and melted fat tail fat in a mass ratio of 1: 1, or

b) a complex of myelin lipids of the peripheral nervous system of animals and melted fat tail fat in a mass ratio of 1: 1.

In a further preferred embodiment, the pharmaceutical composition is in the form of a fat mass in capsules for oral administration.

In another aspect, the claimed invention relates to a method for treating an acute demyelinating condition in a patient in need thereof, the method comprising orally administering to the patient a pharmaceutical composition of the present invention in an amount of 250-500 mg based on the myelin lipid complex of the nervous system of animals 4 times in a day for 6 months, optionally in combination with an adjunct to treat an acute demyelinating condition. As the specified additional agent can be used, in particular, steroidal anti-inflammatory drugs (such as prednisolone, methylprednisolone, etc.), non-steroidal anti-inflammatory drugs (such as acetylsalicylic acid, etc.).

In one preferred embodiment, the claimed method is intended for the treatment of an acute demyelinating condition of the central nervous system, wherein the patient is administered a pharmaceutical composition containing a complex of lipids of the myelin of the central nervous system of animals. In a more preferred embodiment, the acute demyelinating condition of the central nervous system is multiple sclerosis.

In another preferred embodiment, the claimed method is intended for the treatment of an acute demyelinating condition of the peripheral nervous system, wherein the patient is administered a pharmaceutical composition comprising a myelin lipid complex of the peripheral nervous system of animals. In a more preferred embodiment, the acute demyelinating condition of the peripheral nervous system is Guillain-Barré syndrome or leprosy neuropathy.

In another aspect, the claimed invention relates to a method for the prevention of neurodegenerative exacerbations in a patient in need thereof, the method comprising oral administration of the claimed pharmaceutical composition to the patient in an amount of 250-500 mg based on the complex of lipids of the myelin of the nervous system of animals 4 times a day for 3 -12 months.

In one preferred embodiment, the claimed method is intended for the prevention of neurodegenerative exacerbations of the central nervous system, wherein the patient is administered a pharmaceutical composition containing a complex of myelin lipids in the central nervous system of animals. In a more preferred embodiment, the exacerbation of neurodegenerative diseases of the central nervous system is multiple sclerosis.

In another preferred embodiment, the claimed method is intended for the prevention of neurodegenerative exacerbations of the peripheral nervous system, wherein the patient is administered a pharmaceutical composition containing the myelin lipid complex of the peripheral nervous system of animals. In a more preferred embodiment, the exacerbation of neurodegenerative diseases of the peripheral nervous system is Guillain-Barré syndrome or leprosy neuropathy.

The technical result is a new, pathogenetically grounded therapeutic agent that has a regenerating effect on demyelinating damage to the nervous tissue and provides prevention of exacerbations, without unwanted side reactions and restrictions on use.

CARRYING OUT THE INVENTION

The agent for the treatment or prevention of neurodegenerative demyelinating processes of the central and peripheral nervous tissue according to the invention is a complex of myelin lipids of the nervous tissue of animals, consisting of lipid metabolites, cholesterol, phospholipids, growth and differentiation factors, essential fatty acids. To obtain the specified complex, both the nervous tissues of the central nervous system and the nervous tissues of the PNS can be used. As a source of nerve tissue can serve, for example, cattle and small ruminants, pigs. Biological material can be obtained from meat processing plants.

Methods for isolating the total lipid fraction are well known to those skilled in the art and include, in particular, extraction with organic solvents. For example, a chloroform-methanol mixture can be used to isolate a complex of lipids (J. Folch, M. Lees GH Sloane Stanley, A Simple Method for the Isolation and Purification of Total Lipides from Animal Tissues, J. Biol. Chem., 1957 , Vol. 226, p. 497-509). Solvents such as hexane, a mixture of hexane-dichloromethane (RU 2505592), as well as acetone, isopropanol and tert-butanol (RU 2236441) can also be used. A preferred method for isolating the myelin lipid complex of animal nervous tissue is supercritical fluid extraction, in particular using CO ₂ . If necessary, when using supercritical carbon dioxide as a solvent, ethanol is added to it (Roberts S. Dynamic programming in the processes of chemical technology and control methods. M .: Mir, 1965, p. 496).

In the composition of the pharmaceutical composition, the active ingredient, the myelin lipid complex of the nervous tissue of animals, is mixed with pharmaceutically acceptable carriers. Given the lipophilic nature of the active ingredient, various lipophilic compounds such as, for example, fats and oils, which can be of animal, vegetable or synthetic origin, can be used as the carrier. Examples of such carriers are peanut oil, soybean oil, olive oil, sunflower oil, fish liver oil, oil derived from other marine animals or plants, etc. As a preferred carrier in the pharmaceutical composition, fat tail fat can be used.

The pharmaceutical composition can be formulated in various dosage forms, including capsules, soft gelatin capsules, hard gelatin capsules, water-in-oil or oil-in-water emulsions, paste in a tube.

The pharmaceutical composition, in addition to these pharmaceutically acceptable carriers, may additionally contain pharmaceutically acceptable solvents, excipients and other excipients well known to those skilled in the art. In particular, the pharmaceutical composition, if necessary, may contain various non-ionic surfactants (for example, TWIN-80) or ionic surfactants (for example, polyglycerol stearate), as described, for example, in RU 2392949.

A preferred dosage form into which the composition of the present invention can be formulated is an oral capsule containing a fat mass. The pharmaceutical compositions of the present invention can be administered orally as well as by gavage.

The pharmaceutical compositions of the present invention contain the active ingredient, the myelin lipid complex of the nervous system of animals, in a therapeutically effective amount. In a preferred embodiment, the pharmaceutical composition can be formulated to deliver 250-500 mg of active principle when taken in a unit dosage form such as, for example, a capsule. Taking one such capsule 4 times a day will provide a therapeutically or prophylactically effective dose of the active ingredient.

The food compositions of the present invention include foods designed to meet human nutritional requirements. The food compositions can be in a variety of forms, including solid, liquid, and semi-solid. Solid forms of food compositions can be prepared, in particular, in the form of a bar (such as a food bar), chips, baked goods, cracker. Liquid forms can include drinks made in the form of suspensions, emulsions, solutions. Semi-solid forms of food products can be represented, in particular, by pastes, creams, mousses, ice creams, gelatin-based chewing products.

The food compositions of the present invention comprise an effective amount of an animal nervous system myelin lipid complex and a food component. Essentially, the food composition according to the invention is any food product enriched in the myelin lipid complex of the nervous system of animals.

Nutritional supplement means a nutritional composition that generally satisfies a person's specific nutrient requirements but does not significantly contribute to meeting a person's overall nutrient requirements. Nutritional supplements can be provided in various forms, for example, in the form of a pill, a tablet. The nutritional supplement of the present invention contains, as a main component, the myelin lipid complex of the nervous system of animals.

The following examples serve to illustrate some of the most preferred embodiments of the claimed invention, but are not intended to limit the scope of the claims, which is defined by the following claims.

Example 1. Obtaining a complex of myelin lipids of the nervous system of animals.

The agent of the present invention is produced from the tissue of cattle and pigs. The spinal cord (for the CNS myelin lipid complex), the sciatic and thoracic plexus nerves (for the PNS myelin lipid complex) are isolated from slaughtered healthy animals in slaughterhouses. After the separation of the connective tissue, vascular membranes, the tissues are crushed by passing through a meat grinder and, if necessary, stored frozen at -20 ° C until further use. The tissues are then frozen dried under vacuum. To facilitate the extraction of phospholiges, 70% ethyl alcohol is added to the dried tissue in an amount of 10% by volume. Then, total lipids are extracted by supercritical CO ₂ extraction (680-800 bar at 80 ° C). The resulting extract is mixed with melted fat tail fat (180 ° C) in a 1: 1 ratio. After cooling to 50 ° C, it is filled into gelatin capsules.

Example 2. Evaluation of neuroprotective activity of the complex of lipids of myelin of the peripheral nervous system (LAOSCHVANN) on the model of experimental autoimmune neuritis in rats (EAN)

The complex of myelinated lipids of the peripheral nervous system (LAOSCHWANN) was studied in a laboratory model of Guillain-Barré syndrome - experimental autoimmune neuritis (Hahn AF, et al., Experimental allergic neuritis (EAN) as a model for the immune-mediated demyelinating neuropathies.Rev. Neurol. (Paris) 1996 May; 152 (5): 328-32).

Female Wistar rats weighing 200-230 g from the Russian Academy of Sciences Nursery were taken into the study after a 2-week quarantine and divided into the following groups:

1. Control group - 12 goals (K ₁ ), taking "placebo" (corn oil) from the 1st day.

2. Control group - 8 goals (K ₂ ), taking "placebo" from the beginning of the development of EAN symptoms.

3. Experienced - prophylactic group - 12 heads (O ₃ ), taking LAOSCHVAN from the 1st day of immunization.

4. Experienced - treatment group - 12 heads (O ₄ ), taking LAOSCHVANN from the beginning of the development of EAN symptoms.

On the 1st day, animals under anesthesia were injected sc into the hind legs with 200 μl of a mixture of 6 mg of bovine peripheral nerve myelin in 100 μl of phosphate buffer (PB) emulsified with 100 μl of Freund's complete adjuvant (Difco) containing 1 mg / ml of inactivated mycobacterium tuberculosis (H37Ra). Additionally, 3 µg of pertussis toxin was injected intravenously into FB on the 3rd day after immunization. All animals were housed in 4-head cages and provided with free access to food and water. The animals were weighed and clinical signs of disease were examined daily. All experiments were carried out in accordance with the regulations of the Russian Federation for experiments on animals.

The EAN rating scale was used: 0 = no symptoms of the disease, 1+ = tail lethargy, 2+ = moderate paresis of the extremities, 3+ = severe paresis, 4+ = tetraparesis, 5+ = death due to the development of neuropathy.

To assess the prophylactic effect, an experimental group of 12 rats (with induced EAN) received 50 mg of LAOSCHVANN via a gastric tube every day, starting from the 1st day of immunization. Control group - K ₁ of 12 rats received the same amount of placebo (corn oil). To evaluate the therapeutic effect, 12 rats received LAOSCHVANN after the onset of the development of clinical symptoms, i.e. from day 13 after immunization. Control group - K ₂ of 8 animals received the same amount of placebo after the onset of EAN symptoms.

results

Two weeks later (on days 13-14), all 12 animals of the control _{group K 1} (placebo) developed signs of EAN: starting from lethargy of tails and up to the development of paresis by 18 days, one animal died on 20 days, (symptoms of group 3 , 08 ± 0.93), and in the remaining animals, the severity of symptoms began to subside by the 30th day of observation (group symptoms 2.36 ± 0.48). There was a 10% loss in body weight.

All 12 rats of the experimental group - O ₃ , receiving prophylactic LAOSCHVANH from the 1st day of immunization, were protected from the development of clinical symptoms of EAN until the end of the observation period (up to 30 days). Only a 5% lag in weight gain was noted.

In the group - O ₄ experimental animals that received LAOSCHVANN from the beginning of the development of clinical symptoms, i.e. therapeutically, in 1 rat the pathological process of EAN progressed from day 14, and the animal died on day 28 with signs of tetraparesis. In the remaining 11 rats, EAN proceeded in a mild form 1+ (flaccidity of tails) from day 14 and ended with a noticeable improvement on day 30. Group symptoms by day 30 1.09 ± 0.5.

In group K ₂ control animals, who received placebo from the onset of clinical symptoms, the process progressed from day 13 to day 20. Group symptoms by day 30 3.25 ± 0.49. One rat out of 8 died on day 20.

Conclusions: The results of the placebo-controlled study of Laoschwann in laboratory animals with EAN showed a significantly pronounced neuroprotective efficacy. The lipid complex had an inhibitory effect on the development of symptoms of experimental neuritis, both during prophylactic (before the development of EAN symptoms) and therapeutic (from the onset of EAN symptoms) ingestion, without unwanted side reactions.

Example 3. Evaluation of the neuroprotective activity of the complex of lipids of the myelin of the central nervous system (LAOGLIA) on the model of experimental autoimmune encephalomyelitis (EAE) of rats.

The complex of myelin lipids of the central nervous system (LAOGLIA) was investigated on a laboratory model of multiple sclerosis - experimental autoimmune encephalomyelitis (EAE) Kpbic. (Cris S. Constantinescu et al., Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS), Br. J. Pharmacol. 2011 Oct; 164 (4): 1079-1106).

The experiments used female Wistar rats from the Nursery of the Russian Academy of Sciences. After 2 weeks of quarantine, the animals are divided into the following groups.

1. Control group - 12 goals (K ₁ ), taking "placebo" (corn oil) from the 1st day.

2. Control group - 8 goals (K ₂ ), taking "placebo" from the onset of EAE symptoms

3. Experienced - prophylactic group - 12 heads (O ₃ ), taking LAOGLIA from the 1st day of immunization.

4. Experienced - treatment group - 12 heads (O ₄ ), taking LAOGLIA from the beginning of the development of EAE symptoms.

On the 1st day, animals under anesthesia were injected sc into the hind legs with 200 μl of a mixture of 6 mg of bovine spinal cord myelin in 100 μl of phosphate buffer (PB) emulsified with 100 μl of Freund's complete adjuvant (Difco) containing 1 mg / ml of inactivated mycobacterium tuberculosis (H37Ra). Additionally, 3 µg of pertussis toxin was injected intravenously into FB on the 3rd day after immunization. All animals were housed in 4-head cages and provided with free access to food and water. The animals were weighed and clinical signs of disease were examined daily. All experiments were carried out in accordance with the regulations of the Russian Federation for experiments on animals.

The EAE symptom assessment scale was used: 0 = no disease symptoms, 1+ = tail lethargy, 2+ = moderate limb paresis, 3+ = severe paresis, 4+ = tetraparesis, 5+ = death due to neuropathy.

To assess the prophylactic effect, an experimental group of 12 rats (with induced EAE) received 50 mg of LAOGLIA through a gastric tube, every day, starting from the 1st day of immunization. Control group - K ₁ of 12 rats received the same amount of placebo (corn oil). To evaluate the therapeutic effect, 12 rats received LAOGLIA after the onset of the development of clinical symptoms, i.e. from 10 days after immunization. Control group - K ₂ of 8 animals received the same amount of placebo after the onset of EAE symptoms.

results

After 10-11 days, all 12 animals of the control _{group K 1} (placebo) developed signs of EAE: starting from moderate paresis and up to the development of tetraparesis by day 18, 3 animals died on day 24, (group symptoms 3.41 ± 0.51), and in the remaining animals, the severity of symptoms began to subside slightly. By the 30th day of observation, the symptoms of a group of 9 rats were 3.1 ± 1.1. Weight loss was noted by 15%.

All 12 rats of the experimental group - O ₃ , receiving prophylactic LAOGLIA from the 1st day of immunization, were protected from the development of clinical symptoms of EAE until the end of the observation period (up to 30 days). There was only a 15% lag in weight gain.

In the group - O ₄ experimental animals that received LAOGLIA from the beginning of the development of clinical symptoms, i.e. therapeutically, the pathological process of EAE progressed from the 10th to the 15th day. Symptoms peaked at day 15 (3.0 ± 0.66) and slowly subsided. Group symptoms by day 30 1.83 ± 0.73.

In group K ₂ control animals, who received placebo from the onset of clinical symptoms, the process progressed from day 13 to day 20. Group symptoms by day 30 3.50 ± 0.54. Two out of 8 rats died on day 20.

Conclusions: The results of a placebo-controlled study of LAOGLIA in laboratory animals with EAE showed a significantly pronounced neuroprotective efficacy. The lipid complex had an inhibitory effect on the development of symptoms of experimental autoimmune encephalomyelitis, both during prophylactic (before the development of EAE symptoms) and therapeutic (from the beginning of the development of EAE symptoms) ingestion, without unwanted side reactions.

Example 4. Combined treatment regimen using additional anti-inflammatory drugs.

For the treatment of exacerbation of the neurodegenerative process - leprosy erythema nodosum (Type-2 reaction), the following scheme can be used.

1. Methylprednisolone 250 mg intravenously daily for 3 consecutive days.

2. Prednisolone tablets 40 mg per day, starting from the 4th day with a stepwise dose reduction to 5 mg.

3. Aspirin tablets 100 mg per day.

4. Complex of lipids of myelin of the peripheral nervous system (LAOSCHVANN) in capsules of 250 mg 4 times a day for 3 months.

Example 5. The use of a complex of myelin lipids for the prevention of the progression of leprosy neuropathy.

To protect against exacerbations of the neurodegenerative process - (Type-1 and Type-2 reactions) in the process of carrying out specific combined antimycobacterial therapy for patients with leprosy, the following scheme can be used.

1. Daspon 100 mg per day (6 months for TT forms and 12 months for LL forms).

2. Rifampicin 600 mg once a month (6 months for TT forms and 12 months for LL forms).

3. Complex of lipids of myelin of the peripheral nervous system (LAOSCHVANN) in capsules of 250 mg 4 times a day (6 months for TT forms and 12 months for LL forms).

The methods and compositions disclosed herein are not limited to the specific techniques, procedures, and reagents disclosed herein, since, as one skilled in the art will understand, they can be varied. In addition, the terminology used in this description is intended only to describe certain embodiments and is not intended to limit the scope of the claims, which is defined by the claims.

Unless otherwise indicated, all scientific and technical terms and abbreviations used in this description have the meanings that are usually assigned to them by those skilled in the art to which the invention relates, or in the field of technology in which the specified term or abbreviation is used. Preferred compositions, methods, manufactured articles, or other means or materials are presented herein, and it should be understood that other compositions, methods, manufactured articles, or other means or materials similar or equivalent to those described herein may be used in the practice of this invention. description, while remaining within the scope of the claims defined by the claims.

All patents, patent applications, scientific, technical and other publications cited in this description are incorporated by reference. However, they are not intended to constitute prior art in relation to the claimed invention.

Claims (25)

1. The use of a complex of animal myelin lipids, including lipid metabolites, cholesterol, phospholipids, growth factors and differentiation of nervous tissue, essential fatty acids, obtained by drying tissues of the central or peripheral nervous system of animals in frozen form under vacuum, adding 70% ethyl alcohol in an amount 10% by volume, followed by extraction by supercritical extraction of CO ₂ at a pressure of 680-800 bar and a temperature of 80 ° C for the manufacture of a medicinal product for the treatment or prevention of neurodegenerative demyelinating lesions of the nervous tissue. 2. Use according to claim 1, wherein the myelin lipid complex is derived from the central nervous system of the animals. 3. Use according to claim 1, wherein the myelin lipid complex is derived from the peripheral nervous system of the animals. 4. A pharmaceutical composition for the treatment or prevention of neurodegenerative demyelinating lesions of nervous tissue, containing a therapeutically effective amount of a complex of animal myelin lipids, including lipid metabolites, cholesterol, phospholipids, growth factors and differentiation of nervous tissue, essential fatty acids obtained by drying tissues of the central or peripheral nervous system animals frozen in vacuo, add 70% ethanol in an amount of 10% by volume, followed by extraction by a supercritical extraction with CO ₂ at a pressure of 680-800 bar and a temperature of 80 ° C, and a pharmaceutically acceptable carrier comprising a fat base. 5. The pharmaceutical composition of claim 4, wherein the myelin lipid complex originates from the central nervous system of the animals. 6. The pharmaceutical composition of claim 4, wherein the myelin lipid complex is derived from the peripheral nervous system of the animals. 7. A pharmaceutical composition according to claim 4, wherein the fat base comprises melted fat tail fat. 8. The pharmaceutical composition according to claim 7, comprising: a) a complex of myelin lipids of the central nervous system of animals and melted fat tail fat in a mass ratio of 1: 1, or b) a complex of myelin lipids of the peripheral nervous system of animals and melted fat tail fat in a mass ratio of 1: 1. 9. The pharmaceutical composition according to any one of paragraphs. 4-8, made in the form of a fat mass in capsules for oral administration. 10. A method of treating acute neurodegenerative demyelinating damage to nervous tissue in a patient in need thereof, comprising oral administration to the patient of a pharmaceutical composition according to any one of claims. 4-9 in the amount of 250-500 mg based on the complex of lipids of the myelin of the nervous system of animals 4 times a day for 6 months. 11. The method according to claim 10, wherein said neurodegenerative demyelinating damage to the nervous tissue in the patient is a neurodegenerative demyelinating damage to the central nervous system, for the treatment of which the patient is administered a pharmaceutical composition containing a complex of animal central nervous system myelin lipids. 12. The method of claim 11, wherein said neurodegenerative demyelinating damage to the central nervous system is multiple sclerosis. 13. The method according to claim 10, wherein said neurodegenerative demyelinating damage to the nervous tissue in the patient is a neurodegenerative demyelinating injury of the peripheral nervous system, for the treatment of which the patient is administered a pharmaceutical composition containing a complex of myelin lipids of the peripheral nervous system of animals. 14. The method of claim 13, wherein said neurodegenerative demyelinating injury to the peripheral nervous system is Guillain-Barré syndrome or leprosy neuropathy. 15. The method of claim 10, further comprising administering an additional agent for treating acute neurodegenerative demyelinating damage to nerve tissue. 16. The method of claim 15, wherein the additional agent for treating acute neurodegenerative demyelinating damage to nerve tissue is selected from the group consisting of steroidal anti-inflammatory agents and non-steroidal anti-inflammatory agents. 17. The method of claim 16, wherein the steroidal anti-inflammatory agent is selected from the group consisting of methylprednisolone and prednisolone. 18. The method of claim 16, wherein the non-steroidal anti-inflammatory agent comprises acetylsalicylic acid (aspirin). 19. A method of preventing exacerbations of neurodegenerative demyelinating damage to nervous tissue in a patient in need thereof, comprising oral administration to the patient of a pharmaceutical composition according to any one of claims. 4-9 in the amount of 250-500 mg based on the complex of lipids of the myelin of the nervous system of animals 4 times a day for 3-12 months. 20. The method according to claim 19, wherein said neurodegenerative demyelinating damage to the nervous tissue in the patient is a neurodegenerative demyelinating damage to the central nervous system, for the prevention of exacerbation of which the patient is administered a pharmaceutical composition containing a complex of myelin lipids of the central nervous system of animals. 21. The method of claim 20, wherein said neurodegenerative demyelinating central nervous system injury is multiple sclerosis. 22. The method according to claim 19, said neurodegenerative demyelinating damage to the nervous tissue in the patient is a neurodegenerative demyelinating damage to the peripheral nervous system, for the prevention of exacerbation of which the patient is administered a pharmaceutical composition containing a complex of myelin lipids of the central nervous system of animals. 23. The method of claim 22, wherein said neurodegenerative demyelinating injury to the peripheral nervous system is Guillain-Barré syndrome or leprosy neuropathy.