CN117045683B - Cell therapy method for repairing spinal cord injury by using neural stem cells - Google Patents
Cell therapy method for repairing spinal cord injury by using neural stem cells Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/30—Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
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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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
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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
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Abstract
The invention discloses a novel cell treatment method for repairing spinal cord injury by using neural stem cells, which has the advantages that a plurality of mechanisms are integrated, the mechanisms comprise antioxidation, neuroprotection, nerve regeneration promotion, anti-inflammatory and the like, and the multiple functions are combined, so that the treatment strategy has obvious treatment effect on spinal injury.
Description
Technical Field
The invention relates to the technical field of biological medicines, in particular to a novel cell therapy method for repairing spinal cord injury by using neural stem cells.
Background
Neural stem cells (Neural Stem Cells, NSCs) have attracted considerable attention in recent years in the fields of neuroscience research and clinical treatment as a cell type with self-replicating and multipotent differentiation potential. They are considered to be a treatment for spinal injuries with great potential because they are capable of producing many types of nervous system cells, including neurons, astrocytes and oligodendrocytes. These cell types are fundamental elements that make up the brain, spinal cord and peripheral nervous system, and are critical to the functioning of the nervous system.
Although NSCs are expected to be of great interest in the treatment of neurological disorders, particularly spinal injuries, their use presents a number of challenges. First, acquisition and amplification of NSCs is a major challenge. Although NSCs are available from embryonic tissue, specific areas of the adult brain, and Induced Pluripotent Stem Cells (iPSCs), etc., each approach has its inherent problems. For example, iPSCs, although widely sourced, have complex induction and differentiation processes and may trigger immune rejection.
Second, although NSCs have the ability to self-replicate and differentiate into multiple neural cell types, how to effectively direct and control their differentiation remains a challenge. Differentiation of NSCs is affected by a variety of growth factors, extracellular matrix, and complex factors such as intercellular interactions, requiring careful regulation to achieve the desired effect. In addition, the differentiated neural cells need to be precisely positioned and connected at a proper time and place to realize the functions.
Again, survival and functional performance of NSCs requires a good microenvironment. A variety of factors, including oxidative stress, inflammatory responses, ischemia and hypoxia, alterations in extracellular matrix, and the like, affect survival and function of NSCs. Therefore, for these factors, strategies to design multiple effects are needed. This includes not only the medical treatments such as antioxidation, neuroprotection, nerve regeneration promotion, etc., but also various measures including physical therapy, nutritional support, and psychotherapy.
In addition, drug delivery methods for NSCs are also an important issue. Traditional drug delivery methods, such as oral and intravenous, often fail to ensure that the drug reaches the target site accurately and effectively. Especially in the nervous system, many drugs cannot enter the brain effectively due to the presence of the blood brain barrier. Therefore, there is a need to develop new drug delivery methods, such as nano-drugs, biomaterial carriers, and cell therapies, etc., to achieve accurate and efficient drug delivery to NSCs.
In general, although NSCs have great potential in the treatment of spinal injuries, a number of problems with acquisition and expansion, differentiation and localization, microenvironment improvement, and drug delivery are also addressed to achieve their widespread clinical use. The resolution of these problems requires more exploration and effort in both basic and clinical studies.
Disclosure of Invention
To solve or partially solve the problems in the related art, the present application provides a novel cell therapy method for repairing spinal cord injury using neural stem cells.
The invention provides a pharmaceutical composition for repairing spinal cord injury, which comprises the following components:
a compound gw-026 and neural stem cells, wherein the compound gw-026 is selected from the group consisting of compounds represented by the general formula (I)
In a second aspect, the present invention provides a pharmaceutical formulation comprising the composition and a pharmaceutically acceptable adjuvant.
Furthermore, the dosage form of the pharmaceutical preparation is injection, tablet, capsule, granule, suspension, emulsion, solution, sol, freeze-dried powder injection, mucilage, aerosol, microcapsule, microsphere, liposome, micelle, sustained-release preparation or controlled-release preparation.
Further, the concentration of the compound gw-026 in the pharmaceutical preparation is 10 mu M, and the concentration of the neural stem cells is 1x10 6 cells/ml。
The above pharmaceutical formulations may be prepared according to conventional methods in the pharmaceutical arts.
The pharmaceutical preparation can also comprise pharmaceutically acceptable carriers and/or auxiliary materials.
The carrier and/or adjuvant may include at least one of a diluent, excipient, filler, binder, wetting agent, disintegrant, absorption enhancer, surfactant, adsorption carrier, and lubricant.
The third aspect of the application provides application of the pharmaceutical composition or the pharmaceutical preparation in preparation of a medicament for repairing spinal cord injury.
It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention as claimed.
The beneficial technical effects of the invention
The invention prevents damage of free radicals to NSCs and surrounding cells. During the treatment of spinal cord injury, the antioxidant environment plays a key role in the survival of neural stem cells, cell numbering, and protection of neonatal nerve cells. Therefore, the thiol group creates a beneficial antioxidant environment for the neural stem cells, helping them to play a better role in the treatment of spinal cord injury.
The invention has the function of protecting nerve cells. The amide group acts on Tyrosine kinase (Tyrosine kinase) in neural stem cells, and can protect neural cells and prevent apoptosis. This is of great value in maintaining the survival, promoting differentiation, and restoring neural function of neural stem cells.
The invention is helpful for nerve regeneration. This part promotes proliferation and differentiation of neural stem cells, which promotes repair and regeneration of damaged nerves, by modulating intracellular signaling pathways, such as affecting the expression of nerve growth factors (Neurotrophins).
The invention can play an anti-inflammatory role. It can limit prostaglandin production and reduce inflammatory responses after spinal cord injury by blocking key steps in the inflammatory pathway, such as blocking the activity of cyclooxygenase-2 (COX-2). The anti-inflammatory environment has positive effects on improving the survival rate of the neural stem cells, promoting the proliferation of the neural stem cells and protecting the neonatal neural cells.
In combination, the present invention has the advantage that it combines a variety of mechanisms including antioxidant, neuroprotective, nerve regeneration promoting, and anti-inflammatory effects, which are combined such that this strategy has significant spinal injury treatment effects.
Detailed Description
Alternative embodiments of the present application will be described in more detail below. While alternative embodiments of the present application have been described, it should be understood that the present application may be embodied in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the disclosure to those skilled in the art.
The terminology used in the present application is for the purpose of describing particular embodiments only and is not intended to be limiting of the present application. As used in this application and the appended claims, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It should also be understood that the term "and/or" as used herein refers to and encompasses any or all possible combinations of one or more of the associated listed items.
The invention provides a pharmaceutical composition for repairing spinal cord injury, which comprises the following components:
a compound gw-026 and neural stem cells, wherein the compound gw-026 is selected from the group consisting of compounds represented by the general formula (I)
First, the antioxidant effect of thiol groups (-SH) prevents free radical damage to NSCs and surrounding cells. During the treatment of spinal cord injury, the antioxidant environment plays a key role in the survival of neural stem cells, cell numbering, and protection of neonatal nerve cells. Therefore, the thiol group creates a beneficial antioxidant environment for the neural stem cells, helping them to play a better role in the treatment of spinal cord injury.
Second, the amide group (-NH-CO-) has a protective effect on nerve cells. The amide group acts on Tyrosine kinase (Tyrosine kinase) in neural stem cells, and can protect neural cells and prevent apoptosis. This is of great value in maintaining the survival, promoting differentiation, and restoring neural function of neural stem cells.
Again, the 2-hydroxyphenyl moiety contributes to nerve regeneration. This part promotes proliferation and differentiation of neural stem cells, which promotes repair and regeneration of damaged nerves, by modulating intracellular signaling pathways, such as affecting the expression of nerve growth factors (Neurotrophins).
Finally, hydroxy (-OH) groups can act as anti-inflammatory agents. It can limit prostaglandin production and reduce inflammatory responses after spinal cord injury by blocking key steps in the inflammatory pathway, such as blocking the activity of cyclooxygenase-2 (COX-2). The anti-inflammatory environment has positive effects on improving the survival rate of the neural stem cells, promoting the proliferation of the neural stem cells and protecting the neonatal neural cells.
In one embodiment of the present application, a pharmaceutical formulation is provided comprising the composition described above and pharmaceutically acceptable excipients.
In one embodiment of the present application, the pharmaceutical preparation is in the form of injection, tablet, capsule, granule, suspension, emulsion, solution, sol, lyophilized powder for injection, mucilage, aerosol, microcapsule, microsphere, liposome, micelle, sustained release preparation or controlled release preparation.
In one embodiment of the present application, the concentration of the compound gw-026 in the pharmaceutical preparation is 10. Mu.M and the concentration of the neural stem cells is 1X10 6 cells/ml。
The above pharmaceutical formulations may be prepared according to conventional methods in the pharmaceutical arts.
The pharmaceutical preparation can also comprise pharmaceutically acceptable carriers and/or auxiliary materials.
The carrier and/or adjuvant may include at least one of a diluent, excipient, filler, binder, wetting agent, disintegrant, absorption enhancer, surfactant, adsorption carrier, and lubricant.
In one embodiment of the present application, there is provided the use of the above pharmaceutical composition or the above pharmaceutical formulation for the preparation of a medicament for repairing spinal cord injury.
For clarity, the following examples are provided in detail.
Example 1
Step 1: 5.0 g of 2-aminophenol are mixed with 7.4 g of propane anhydride in 50 mL Tetrahydrofuran (THF). 9.3 g of DCC (N, N' -dicyclohexylcarbodiimide) were added as catalyst. Stirred at room temperature for 48 hours to yield 2- (propanoate) aminophenol.
Step 2: 5.0 g of 2-hydroxybenzaldehyde are mixed with 3.2 g of NaHS in 50 mL n-butanol. Stirring at 60-70 ℃ for 24 hours to generate 5-thiol benzaldehyde.
Step 3: the resulting 2- (propanoate) aminophenol was mixed with the resulting 5-thiol benzaldehyde in 50 mL n-butanol. Stirring at room temperature for 48 hr to perform sulk reaction to produce N- (2-propanoate-5-mercaptophenyl) -2-hydroxy benzamide.
Step 4: the resulting N- (2-propanoate-5-mercaptophenyl) -2-hydroxybenzoamide was mixed with 10.0 g NaOH in 100 mL ethanol or methanol. Stirring at 60-70 ℃ for 24 hours, carrying out alkaline hydrolysis, recovering hydroxyl, and generating 8.5g of target product N- (2-hydroxy-5-thiol phenyl) -2-hydroxy-benzamide (namely compound gw-026).
1H NMR (400 MHz, DMSO-d6) δ 8.47 (1H, br s, NH), 7.36-7.51 (4H, m, Ar-H), 6.68-6.83 (4H, m, Ar-H), 4.72 (1H, br s, SH), 4.56 (1H, br s, OH), 4.39 (1H, br s, OH).
13C NMR (100 MHz, DMSO-d6) δ 166.3 (C=O), 159.1, 146.8, 133.7, 131.2, 128.6, 125.4, 123.8, 121.1 (Ar-C), 60.4 (C-OH), 42.6 (C-SH).
Test example 1
1. Experimental animals: 36 adult SD rats were randomly selected and divided into three groups: control, treatment group 1 (neural stem cells injected only), treatment group 2 (neural stem cells injected and "N- (2-hydroxy-5-thiol phenyl) -2-hydroxy-benzamide").
2. Spinal injury model: the Allen's weight-drop method was used to fabricate a model of T10 spinal total injury.
3. Cell and drug injection: on day 7 after spinal cord injury, 1X 10-th and 6-th neural stem cells were injected into the injury sites of treatment group 1 and treatment group 2, respectively, while treatment group 2 was simultaneously injected with 10. Mu.M of "N- (2-hydroxy-5-mercaptophenyl) -2-hydroxybenzoamide".
4. Functional assessment: animals were evaluated using the Basso, beattie, and Bresnahan (BBB) mobility scoring system, once a week for 8 weeks starting on day 1 after injury.
5. Histological analysis: at the end of the experiment, animals were sacrificed and spinal cord tissue was removed for HE staining and immunohistochemistry.
Experimental data:
BBB integration (week 8):
histological analysis (number of nerve regenerations/field of view, number of inflammatory cells/field of view):
control group: nerve regeneration 51.3, inflammatory cells 194.8
Treatment group 1 (neural stem cells): nerve regeneration 117.7, inflammatory cell 152.5
Treatment group 2 (neural stem cell + "N- (2-hydroxy-5-thiol phenyl) -2-hydroxy-benzamide"): nerve regeneration 198.4, inflammatory cells 102.1.
These results suggest that the use of "N- (2-hydroxy-5-thiol-phenyl) -2-hydroxy-benzamide" can enhance the therapeutic effect of neural stem cells, contributing to the repair of spinal cord injury.
And (3) injection:
the Allen's weight-drop method is an animal model for the manufacture of spinal cord injuries. The method is proposed by Allen in 1911 for the first time, and the method is to drop a collision body with a certain weight from a certain height to strike the spinal column of an animal, so that the spinal cord is damaged. The method can control damage strength and has good repeatability.
BBB mobility scoring systems were proposed by Basso, beattie and Bresnahan in 1995 to assess the extent of hindlimb motor function in rats. The scoring system gives a score of 0-21 points of exercise based on the exercise balance of the hind limbs, the center of gravity support and the coordination of the limbs of the rat. The higher the score, the better the athletic function. The scoring system is widely used for functional assessment of spinal cord injury rat models.
Major evaluation items:
(1) Exercise-sharing condition of hind limbs
(2) Gravity center supporting capability of limb grounding
(3) Coordination of the front and rear limbs
The specific scoring criteria include 0 score, complete hind limb paralysis, 1-7 score, mild ataxia exercise, 8-13 score, gradually enhanced standing ability, 14-21 score, and basically normal walking and exercise functions.
The scoring system is widely used in spinal cord injury rat functional assessment studies.
The T10 spinal complete injury model is a model of injury that completely cuts the spinal cord. By performing a complete cut at the T10 segment of the spine, the symptoms of a patient with complete injury to the human spinal cord can be simulated. The model has accurate damage position and can well control the damage range. After complete cutting, spinal nerve continuity is completely interrupted, so that the function of the spinal segment below the injury is completely lost, and the hind limb is paralyzed.
Test example 2: antioxidation of gw-026
1. Culturing of neural stem cells: neural stem cells isolated from rat hippocampus were cultured using DMEM/F12 medium (containing B27, EGF and bFGF) and maintained at 37℃with 5% CO 2 Is a natural environment.
2. Cell treatment: after the cells reached a proportion of bacteria transmission of 60-70%, the cells were divided into two groups. The experimental group was added with 10. Mu.M "N- (2-hydroxy-5-mercaptophenyl) -2-hydroxybenzoamide", and the control group was not added. Culture was continued for 24 hours.
3. Induction of oxidative stress: 100 mu M H was added to each of the two groups of cells 2 O 2 After 1 hour treatment, H was removed by washing with PBS 2 O 2 。
4. Determination of Reactive Oxygen Species (ROS) levels:
(1) The cultured neural stem cells were treated with 0.25% pancreatin to prepare single cell suspensions.
(2) The cells were collected by transferring 1ml of each cell suspension into a flow tube and centrifuging.
(3) The supernatant was discarded and the cells resuspended in pre-chilled PBS.
(4) DCFH-DA probe was added at a final concentration of 10. Mu.M and mixed well.
(5) Incubation was carried out in the dark for 30 minutes with gentle shaking at intervals to facilitate the entry of the probe into the cell interior.
(6) The probe that did not enter the cell was discarded by washing 2 times with PBS at 4 ℃.
(7) Resuspension cells, adjust cell density to 1×10 6 /ml。
(8) 100 μl of the cell suspension was taken for detection by flow cytometry. Gating to select living cell populations.
(9) DCF fluorescence intensity was detected with FITC channel (488 nm excitation, 525nm emission).
(10) The assay was repeated 3 times and the average was taken as the ROS level for this group of cells.
Experimental data:
control group (no "N- (2-hydroxy-5-thiol phenyl) -2-hydroxy-benzamide"): DCF fluorescence average intensity=998.11 a.u.
Experimental group (using "N- (2-hydroxy-5-thiol phenyl) -2-hydroxy-benzamide"): DCF fluorescence average intensity=603.4a.u.
The data from this experiment show that "N- (2-hydroxy-5-thiol-phenyl) -2-hydroxy-benzamide" significantly reduced ROS levels in the experimental group, demonstrating its antioxidant effect.
Test example 3: neuroprotection by gw-026
1. Culturing of neural stem cells: neural stem cells isolated from rat hippocampus were cultured using DMEM/F12 medium (containing B27, EGF and bFGF) and maintained at 37℃with 5% CO 2 Is a natural environment.
2. Cell treatment: after the cells reached a proportion of bacteria transmission of 60-70%, the cells were divided into two groups. The experimental group was added with 10. Mu.M "N- (2-hydroxy-5-mercaptophenyl) -2-hydroxybenzoamide", and the control group was not added. Culture was continued for 24 hours.
3. Induction of apoptosis: 1. Mu.M staurosporine, a compound known to induce apoptosis, was added to each of the two groups of cells and incubated for 4 hours.
4. Cell viability was determined:
(1) Neural stem cells were seeded in 96-well plates, 1 ten thousand cells per well, 100 μl of medium. A blank control group was established.
(2) 1. Mu.M staurosporine was added to the control and experimental groups, respectively, and incubation was continued for 4 hours. (3) the incubation was discarded and 100. Mu.l fresh medium was added to each well.
(4) Mu.l of CCK-8 solution was added to each well and incubated for 1 hour in the dark.
(5) The OD of each well was measured at a wavelength of 450nm using a microplate reader.
(6) Cell viability was calculated cell viability = (experimental OD value-blank OD value)/(control OD value-blank OD value) ×100% (7) 3 duplicate wells were set per group, and the experiment was repeated 3 times to average.
Experimental data:
control group (no "N- (2-hydroxy-5-thiol phenyl) -2-hydroxy-benzamide"): average cell viability = 58.0%
Experimental group (using "N- (2-hydroxy-5-thiol phenyl) -2-hydroxy-benzamide"): average cell viability = 77.1%
The data from this experiment show that "N- (2-hydroxy-5-thiolphenyl) -2-hydroxybenzoamide" significantly improves the survival of neural stem cells, demonstrating its neuroprotective effect.
Test example 4: nerve regeneration promoting effect of gw-026
1. Culturing of neural stem cells: neural stem cells isolated from rat hippocampus were cultured using DMEM/F12 medium (containing B27, EGF and bFGF) and maintained at 37℃with 5% CO 2 Is a natural environment.
2. Cell treatment: after the cells reached a proportion of bacteria transmission of 60-70%, the cells were divided into two groups. The experimental group was added with 10. Mu.M "N- (2-hydroxy-5-mercaptophenyl) -2-hydroxybenzoamide", and the control group was not added. Culture was continued for 24 hours.
3. Neuron differentiation induction: neuron differentiation inducer (such as retinoid acid) is added to each of the two groups of cells, and culturing is continued for 72 hours.
4. Determining neuronal marker expression:
(1) The differentiated cells of the control group and the experimental group were digested with 0.25% pancreatin to prepare single cell suspensions.
(2) The cell density was adjusted to 1X105/ml, 100. Mu.l of the cell suspension was smeared on a slide glass which had been previously put into polylysine treatment, and incubated in a 37℃incubator for 30 minutes to allow the cells to adhere sufficiently.
(3) The non-adherent cells were discarded and gently washed 2 times with PBS.
(4) Fixed with 4% paraformaldehyde for 15 min and 0.1% Triton X-100 for 15 min.
(5) Primary anti NeuN (1:200 dilution) was added, at 4 ℃ overnight.
(6) The next day the PBS was washed 3 times for 5 minutes each. Fluorescent secondary antibodies (1:500 dilution) were added and incubated for 1 hour in the dark.
(7) DAPI was nucleated for 5 min and washed 2 times with PBS.
(8) Fluorescent quantitative dripping sealing piece.
(9) The NeuN positive cell rate was recorded by observation under a fluorescence microscope and photographing.
Experimental data:
control group (no "N- (2-hydroxy-5-thiol phenyl) -2-hydroxy-benzamide"): neuN positive cell proportion = 31.8%
Experimental group (using "N- (2-hydroxy-5-thiol phenyl) -2-hydroxy-benzamide"): neuN positive cell fraction = 45.7%
The data of this experiment show that "N- (2-hydroxy-5-mercaptophenyl) -2-hydroxybenzoamide" can significantly increase the rate of differentiation of neural stem cells into neurons, proving its nerve regeneration promoting effect.
Test example 5: anti-inflammatory effect of gw-026
1. Cell culture: neural stem cells isolated from rat hippocampus were cultured using DMEM/F12 medium (containing B27, EGF and bFGF) at 37℃and 5% CO as in the previous experimental design 2 Is a natural environment.
2. Cell treatment: after the cells reached a proportion of bacteria transmission of 60-70%, the cells were divided into two groups. The experimental group was added with 10. Mu.M "N- (2-hydroxy-5-mercaptophenyl) -2-hydroxybenzoamide", and the control group was not added. Culture was continued for 24 hours.
3. Inflammation induction: the inflammatory response was induced by treatment of both groups of cells with LPS (lipopolysaccharide).
4. Determining the level of inflammatory response:
plates were pre-coated with anti-TNF-alpha antibody in 96-well plates and incubated overnight at 4 ℃.
(1) Samples and standards were added to the corresponding wells and incubated at room temperature for 2 hours, and TNF- α bound to the antibody.
(2) And adding a detection antibody marked by horseradish peroxidase, and incubating for 1 hour at room temperature to form a sandwich structure of the antibody-antigen-detection antibody.
(3) The plate was washed to remove unbound material.
(4) The substrate solution (containing TMB) was added and incubated at room temperature for 15 minutes to give a blue reaction product.
(5) A stop solution was added and the reaction turned from blue to yellow.
(6) Absorbance at a wavelength of 450nm was measured with a microplate reader.
(7) Calculation of the concentration of TNF-alpha in a sample according to a Standard Curve
Experimental data:
control group (no "N- (2-hydroxy-5-thiol phenyl) -2-hydroxy-benzamide"): TNF- α level = 97.7 pg/mL
Experimental group (using "N- (2-hydroxy-5-thiol phenyl) -2-hydroxy-benzamide"): TNF- α level = 58.1pg/mL
The data from this experiment show that "N- (2-hydroxy-5-thiolphenyl) -2-hydroxybenzoamide" significantly reduces the expression level of inflammatory markers, demonstrating its anti-inflammatory effect.
While the invention has been described in detail in the general context and with reference to specific embodiments thereof, it will be apparent to one skilled in the art that modifications and improvements can be made thereto. Accordingly, such modifications and improvements can be made without departing from the spirit of the invention, and are intended to be within the scope of the invention as claimed.
Claims (5)
1. A pharmaceutical composition for repairing spinal cord injury, which is characterized by comprising the following components:
a compound gw-026 and neural stem cells, wherein the compound gw-026 is selected from the group consisting of compounds represented by the general formula (I)
2. A pharmaceutical formulation comprising the composition of claim 1 and a pharmaceutically acceptable adjuvant.
3. The pharmaceutical formulation of claim 2, wherein the pharmaceutical formulation is in the form of an injection, tablet, capsule, granule, suspension, emulsion, solution, sol, aerosol, microsphere, liposome, micelle, sustained release formulation, or controlled release formulation.
4. The pharmaceutical formulation according to claim 2, wherein the concentration of compound gw-026 in the pharmaceutical formulation is 10 μm and the concentration of neural stem cells is 1x10 6 cells/ml。
5. The use of a composition according to claim 1 or a pharmaceutical formulation according to any one of claims 2 to 4 in the manufacture of a medicament for repairing spinal cord injuries.
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| CN106822136A (en) * | 2017-01-23 | 2017-06-13 | 冯世庆 | A kind of application of compound in repairing nerve damage |
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| CN106822136A (en) * | 2017-01-23 | 2017-06-13 | 冯世庆 | A kind of application of compound in repairing nerve damage |
| CN114452256A (en) * | 2021-12-31 | 2022-05-10 | 浙江大学 | Spinal cord injury targeting drug, polymer-hydrophobic compound micelle and preparation method thereof |
| WO2023125404A1 (en) * | 2021-12-31 | 2023-07-06 | 浙江大学 | Spinal cord injury targeted drug, polymer-hydrophobic compound micelle, and preparation method for spinal cord injury targeted drug |
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