CN118593449A - Application of exosomes in the preparation of drugs for treating nervous system diseases - Google Patents

Abstract

The present invention relates to a technical field of exosome application, specifically to an application of exosomes in the preparation of drugs for treating nervous system diseases. Exosome-mediated cell communication has advantages over paracrine signals and endocrine signals, because each exosome may transmit more than one piece of information and play a regulatory role at different stages of gene expression. Taking stem cell exosomes, which have the most application prospects, as an example, stem cell exosome-mediated cell communication participates in many physiological processes. Exosomes have natural targeting capabilities and can accurately deliver drugs to lesions. Exosomes can freely cross the blood-brain barrier, solving the problem that existing drugs are difficult to enter the brain to exert their efficacy. Exosomes have good biocompatibility and biodegradability, reducing drug damage to normal cells and reducing the occurrence of side effects. The present invention can be administered in a variety of ways, such as intravenous injection and nasal drops, and is suitable for different patient groups.

Description

Application of exosomes in the preparation of drugs for treating nervous system diseases

Technical Field

The present invention relates to the technical field of exosome application, and specifically to the application of exosomes in the preparation of drugs for treating nervous system diseases.

Background Art

As we all know, with the deepening of biomedical research, the treatment of neurological diseases has become a major challenge in the medical field. At present, the treatment options for neurological diseases mainly include drug therapy, surgical treatment and physical therapy.

However, these drugs often have disadvantages such as large side effects, unstable effects, and difficulty in passing the blood-brain barrier, resulting in unsatisfactory treatment effects. In particular, there is still a lack of specific drugs on the market for neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, and acute nervous system injuries such as stroke. In order to alleviate the pain caused by nervous system diseases to patients as soon as possible, the application of exosomes in the preparation of drugs for the treatment of nervous system diseases is proposed.

Summary of the invention

The purpose of the present invention is to provide an application of exosomes in the preparation of drugs for treating nervous system diseases, which solves the problem that the diseased body cannot be accurately treated in the background art.

In order to solve the above technical problems, the present invention provides the following technical solutions:

An application of exosomes in the preparation of drugs for treating nervous system diseases. Exosomes refer to membrane vesicles containing complex RNA and proteins, with a diameter of about 30-150nm.

Preferably, there are many drugs for treating nerves, such as vitamin B1, vitamin B6, vitamin B12, methylcobalamin, etc., which nourish nerves and promote nerve conduction and are used for peripheral nerve injury. Oryzanol can regulate autonomic dysfunction and is clinically used to treat neurasthenia, poor sleep, menopausal syndrome, etc. Due to its ability to dilate microvessels, dimethoate is also mainly used for peripheral nerve diseases. Mouse nerve growth factor for injection is mostly used for toxic peripheral neuropathy. Monosialotetrahexosylganglioside sodium injection can promote the recovery of nerve function and is used for central nervous system lesions, including cerebral spinal cord injury and Parkinson's disease patients. Brain protein hydrolysate contains small molecule polypeptides and amino acids, which improve brain metabolism and nourish brain nerves. Oxiracetam is used to treat neurological dysfunction and memory and intellectual impairment caused by brain injury. Idebenone protects mitochondrial function and improves oxygen metabolism, and is used to treat Alzheimer's disease, vascular dementia and sequelae of stroke.

Preferably, the exosomes first pass through the cell membrane invagination, complete the packaging process inside the cell and are then released outside the cell. This process allows the exosomes to carry RNA, proteins, and a small amount of DNA related to the expression of genetic information. Therefore, the transfer of exosomes can achieve material transport and information transmission between cells. The structure of exosomes is also very stable, and the contents that can be encapsulated are also very rich.

Preferably, exosome-mediated cell communication has advantages over paracrine signals and endocrine signals, because each exosome may transmit more than one message and play a regulatory role at different stages of gene expression. Taking stem cell exosomes, which have the most application prospects, as an example, stem cell exosome-mediated cell communication is involved in many physiological processes, including immune regulation, tumor progression, tissue regeneration, reprogramming, differentiation, telomere function and aging, and has therefore been applied to the treatment of various aging-related diseases such as cardiovascular disease, skin diseases, diabetes, osteoarthritis, etc.

Preferably, natural exosomes can cross the blood-brain barrier, and its mechanism is mainly related to the interaction between the surface ligands of exosomes and the surface receptors of brain vascular endothelial cells. Exosomes can carry drugs to the location of the lesion for precise treatment.

Compared with the prior art, the beneficial effects achieved by the present invention are:

1. Precise targeting: Exosomes have natural targeting capabilities and can accurately deliver drugs to the lesion site, improving the therapeutic effect.

2. Crossing the blood-brain barrier: Exosomes can freely cross the blood-brain barrier, solving the problem that existing drugs are difficult to enter the brain to exert their efficacy.

3. Reduce side effects: Exosomes have good biocompatibility and biodegradability, which reduces the damage of drugs to normal cells and reduces the occurrence of side effects.

4. Various modes of administration: The present invention can be administered in a variety of ways, such as intravenous injection and nasal drops, which is convenient and flexible and suitable for different patient groups.

DETAILED DESCRIPTION

The technical solutions in the embodiments of the present invention are described clearly and completely. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

An application of exosomes in the preparation of drugs for treating nervous system diseases. Exosomes refer to membrane vesicles containing complex RNA and proteins, with a diameter of about 30-150nm. Exosomes are mainly extracted from hematopoietic stem cells and blood supernatant. The extracted exosomes need to be used as soon as possible to avoid losing activity and reducing the effect of use. The method for extracting exosomes is:

Ultracentrifugation: Currently the gold standard for exosome isolation and the most commonly used method for exosome extraction, the method is mature and suitable for large volume samples.

Precipitation method: simple operation, fast and high recovery rate.

Ultrafiltration method: The operation is simple and time-saving, and exosomes can be obtained at a low speed without affecting the biological activity of exosomes.

Affinity chromatography: ensures the integrity of exosome morphology, high specificity, simple operation, and no need for special and expensive instruments and equipment.

Among the above methods, the purity of extraction by methods one, two, and three is not enough, and the amount extracted by method four is not enough. We can combine these two groups of methods, first use methods one, two, and three to roughly extract exosomes, and then use method four to purify the exosomes.

There are many drugs for treating nerves, such as vitamin B1, vitamin B6, vitamin B12, methylcobalamin, etc., which nourish nerves and promote nerve conduction and are used for peripheral nerve damage. Oryzanol can regulate autonomic dysfunction and is clinically used to treat neurasthenia, poor sleep, menopausal syndrome, etc. Dibazole is also mainly used for peripheral nerve diseases because it dilates microvessels. Mouse nerve growth factor for injection is mostly used for toxic peripheral neuropathy. Monosialotetrahexosylganglioside sodium injection can promote the recovery of nerve function and is used for central nervous system lesions, including cerebrospinal cord. For patients with injury diseases and Parkinson's disease, brain protein hydrolysate contains small molecule peptides and amino acids, which improve brain metabolism and nourish brain nerves. Oxiracetam is used to treat neurological dysfunction and memory and intellectual impairment caused by brain injury. Idebenone protects mitochondrial function and improves oxygen metabolism. It is used to treat Alzheimer's disease, vascular dementia and sequelae of stroke. Drugs that usually treat the nervous system have side effects, which can cause patients to have emotional instability, such as vivid hallucinations, fragmentary delusions and corresponding changes in emotions and behaviors, and can also make people prone to symptoms such as excitement or addiction.

Exosomes first pass through the cell membrane invagination, complete the packaging process inside the cell and are then released outside the cell. This process allows the exosomes to carry RNA, proteins, and a small amount of DNA related to the expression of genetic information. Therefore, the transfer of exosomes can achieve material transport and information transmission between cells. The structure of exosomes is also very stable, and the contents that can be encapsulated are also very rich. Exosomes are a medium for cell communication and can also be used as a carrier.

Exosome-mediated cell communication has advantages over paracrine and endocrine signals, because each exosome may transmit more than one piece of information and play a regulatory role at different stages of gene expression. Taking stem cell exosomes, which have the most application prospects, as an example, stem cell exosome-mediated cell communication is involved in many physiological processes, including immune regulation, tumor progression, tissue regeneration, reprogramming, differentiation, telomere function and aging. Therefore, it has been applied to the treatment of various aging-related diseases such as cardiovascular disease, skin diseases, diabetes, osteoarthritis, etc. Due to the natural barriers of the human nervous system, insufficient medication will result in no useful effect on the treatment of neurological diseases, and increasing the dosage will lead to side effects. Therefore, exosomes are used as carriers to open up communication between cells, so that the treatment of neurological diseases can achieve the desired effect. Exosomes are used as drug transport carriers, which have unique advantages such as low immunogenicity, high transport efficiency, good stability, strong targeting, and the ability to cross the blood-brain barrier.

Natural exosomes can carry drugs across the blood-brain barrier. The mechanism is mainly related to the interaction between the exosome surface ligands and the surface receptors of brain vascular endothelial cells. Exosomes can carry drugs to the lesion site for precise treatment. First, the exosomes are mixed with the drugs. Drug screening: According to the type and pathological characteristics of the neurological disease, targeted therapeutic drugs are screened.

Drug modification: Make necessary chemical modifications to the screened drugs to enhance their binding ability and stability with exosomes.

Exosome extraction: Exosomes are extracted from cell culture fluid or biological samples using appropriate methods.

Drug-exosome binding: The modified drug is effectively combined with exosomes through physical or chemical methods.

Generally speaking, exosomes need to be extracted from the patient's own cells to prevent rejection and other factors that affect the treatment effect.

The exosomes are then targeted and modified, and appropriate targeting molecules are selected, modified, and then combined with the exosomes. Finally, different delivery methods are adopted to deliver the modified exosomes into the patient's body.

S1. Site disinfection: The puncture site should be disinfected repeatedly with iodine or alcohol 2-3 times, and puncture should be performed after the disinfectant liquid has basically evaporated.

S2. Puncture: After seeing blood return during puncture, temporarily open the infusion set, quickly fix the puncture needle, loosen the tourniquet, and wait for the infusion drug to drip in smoothly before further fixing the needle.

Finally, appropriate efficacy evaluation will be conducted based on the type of mental illness and case characteristics of different patients. Patients will be followed up regularly after treatment to record and observe their negative reflections and daily conditions. Finally, the collected data will be organized, analyzed and evaluated to determine the efficacy and safety of exosomes in the preparation of drugs for the treatment of neurological diseases.

While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that many changes, modifications, substitutions and alterations may be made to the embodiments without departing from the principles and spirit of the present invention, the scope of which is determined by the appended claims and their equivalents.

Claims (7)

1. An application of exosomes in preparing a medicament for treating neurological diseases, characterized in that: exosomes, which are membranous vesicles comprising complex RNAs and proteins, have diameters of about 30-150 nm.

2. Use of an exosome according to claim 1 for the preparation of a medicament for the treatment of neurological disorders, characterized in that: many drugs for treating nerve, such as vitamin B1, vitamin B6, vitamin B12, mecobalamin and other trophic nerves, promote nerve conduction, are used for peripheral nerve injury, oryzanol can regulate vegetative nerve dysfunction, is clinically used for treating neurasthenia, poor sleep, climacteric syndrome and the like, and is mainly used for treating peripheral nerve diseases due to the expansion of micro-blood vessels of the dibazol, the injection of mouse nerve growth factors is mainly used for treating toxic peripheral nerve diseases, the monosialotetrahexosyl ganglioside sodium injection can promote the recovery of nerve functions and is used for treating central nervous system lesions, including cerebral spinal cord injury diseases and parkinsonism patients, brain protein hydrolysate contains micromolecular polypeptides and amino acids, improves brain metabolism, nourishes brain nerves, and is used for treating nerve function deficiency and memory and intelligent disorder caused by brain injury, idebenone protects mitochondrial functions, improves oxygen metabolism, and is used for treating senile dementia, vascular dementia and apoplexy sequelae.

3. Use of an exosome according to claim 2 for the preparation of a medicament for the treatment of neurological disorders, characterized in that: the exosome is first sunk in cell membrane and then released to cell outside after finishing the packing process in cell, and this process makes the exosome carry RNA, protein and small amount of DNA relevant to the expression of genetic information, so that the transfer of exosome can realize the material transportation and information transfer between cell, and the structure of exosome is very stable and the packed content is also very rich.

4. Use of an exosome according to claim 3 for the manufacture of a medicament for the treatment of neurological disorders, characterized in that: exosome-mediated cellular communication is advantageous over paracrine and endocrine signals, because each exosome may transmit more than one message and exert its regulatory effects at different stages of gene expression, and for example, stem cell exosome-mediated cellular communication, which has the greatest application prospects, is involved in many physiological processes including immunomodulation, tumor progression, tissue regeneration, reprogramming, differentiation, telomere function and aging, and thus is also applied to the study of treatment of various aging-related diseases such as cardiovascular disease, skin disease, diabetes, osteoarthritis, and the like.

5. The use of an exosome according to claim 4 for the manufacture of a medicament for treating a neurological disorder, wherein: the natural exosomes can cross the blood-brain barrier, the mechanism of the exosomes is mainly related to the interaction between the exosome surface ligand and the brain vascular endothelial cell surface receptor, and the exosomes can carry medicines to reach the lesion position for accurately treating the exosomes.

6. The use of an exosome according to claim 5 for the manufacture of a medicament for treating a neurological disorder, wherein: exosome acquisition:

Sample type Sample volume NTA particle count Particles/mL Particle size distribution nm Protein amount ug Cell supernatant 1mL 108-109 90-130 ～10 Blood 1mL 1010-1011 60-100 200-400

7. The use of an exosome according to claim 6 in the manufacture of a medicament for treating a neurological disorder, comprising the steps of:

S1, part disinfection: repeatedly sterilizing the puncture part with iodophor or alcohol for 2-3 times, and performing puncture after the sterilized liquid is basically volatilized.

S2, puncturing: after puncture and blood return, the infusion apparatus can be temporarily opened, the puncture needle can be quickly fixed, the tourniquet is loosened, and the needle is further fixed when the infusion medicine is dripped smoothly.