CN108653274B - Application of arctigenin in preparation of medicine for treating bone marrow injury - Google Patents

Application of arctigenin in preparation of medicine for treating bone marrow injury Download PDF

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CN108653274B
CN108653274B CN201710211087.0A CN201710211087A CN108653274B CN 108653274 B CN108653274 B CN 108653274B CN 201710211087 A CN201710211087 A CN 201710211087A CN 108653274 B CN108653274 B CN 108653274B
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arctigenin
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张贵民
孙成宏
刘艳松
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Lunan Pharmaceutical Group Corp
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Abstract

The invention belongs to the field of medicines, and relates to medical application of arctigenin, in particular to application of arctigenin in preparing a medicine for treating spinal cord injury. Has definite curative effect on the aspect of treating spinal cord injury and has great development and application values.

Description

Application of arctigenin in preparation of medicine for treating bone marrow injury
Technical Field
The invention belongs to the field of medicines, relates to a medical application of arctigenin, and particularly relates to an application of arctigenin in preparing a medicine for treating spinal cord injury.
Background
Acute Spinal Cord Injury (SCI) is a common injury in the clinic, and in addition to death, the injury often causes motor function impairment and even paralysis, sensory function impairment, and neuropathic pain in the injured person. And most of the labor is generated in young people, so that the life quality of patients is greatly reduced, and meanwhile, the loss of labor force and the increase of medical expenses cause great burden to the society. The pathological course of SCI is generally divided into stages: primary injury and secondary injury. Primary injury is irreversible. Secondary injury refers to mechanical damage that causes a series of deleterious biochemical reactions to diffuse from the initial site to adjacent tissues. By inhibiting the progression of secondary injury, further deterioration of the disease can be prevented and functional recovery can be promoted. Treatment and functional recovery of SCI is still a worldwide problem.
Chronic compressive Spinal Cord Injury (SCI) is one of the common and frequent diseases of the middle-aged and the elderly, and can cause paraplegia and quadriplegia of the patients, so that the patients lose labor and life abilities, and the SCI becomes a social problem. Whether damaged spinal nerve cells can regenerate and repair spinal functions and the recovery mechanism of SCI are always hot topics which are concerned about the world and are also the research direction of SCI established by the International spinal trust Foundation. The traditional treatment method for chronic SCI mainly adopts operation to relieve compression, can obviously improve symptoms, but has no satisfactory curative effect on the secondary injury reaction. Traditional medicine, particularly acupuncture, has made a great deal of work in the treatment and research of SCI. It has been proved by a long-standing and extensive clinical practice that acupuncture has undoubted curative effects on improvement of sensory, motor and sphincter dysfunction and other complications caused by spinal cord injury, such as myospastic pain, disfunction of the bowels, paralysis of the lower limbs, etc., and is an important means for treating SCI. However, studies on the mechanism of needle stick treatment of spinal cord injury are currently in the sprouting stage. Decompression in the treatment of chronic spinal cord injury by acupuncture also lacks corresponding experimental basis.
In recent years, the treatment of spinal cord injury by traditional Chinese medicines has become a new research hotspot at home and abroad, and the application research of the traditional Chinese medicines such as salvia miltiorrhiza, ligusticum wallichii, safflower, astragalus mongholicus and the like and extracts thereof greatly widens the treatment idea of SCI. The fructus arctii is dry mature fruit of a two-year-old plant of the Compositae, is a traditional Chinese medicine in China, and is mainly used for treating wind-heat type common cold, measles, rubella, sore throat, carbuncle, swelling, sore and the like. Arctigenin is a main active ingredient extracted from fructus arctii, is a plant-derived lignan compound, and has stronger pharmaceutical activity than arctiin. Research shows that the compound has biological activities of anti-inflammation, immunoregulation, antivirus, antitumor, neuroprotection and the like. However, there is no report that arctigenin is used for spinal cord injury.
Disclosure of Invention
In order to solve the problem of treatment of the SCI, the invention provides a pharmaceutical preparation containing arctigenin, the arctigenin can be prepared into a proper pharmaceutical preparation for treatment of spinal cord injury, for example, the arctigenin can be developed into an oral preparation or an injection preparation for use by patients conveniently, wherein the oral preparation comprises tablets, capsules, granules, oral micro-emulsion and the like, and each preparation unit of the oral preparation contains 0.01-200 mg of pharmaceutical active ingredient arctigenin. The injection preparation comprises injection and injection microemulsion. When the arctigenin is prepared into injection, the pharmaceutically acceptable carrier may be one or more of water for injection, sodium chloride, sodium citrate, citric acid, glycerol, ethanol, propylene glycol, and PEG-400. The arctigenin injection can be added with appropriate additives according to the properties of the medicine, such as osmotic pressure regulator, pH regulator, solubilizer, antioxidant, bacteriostatic agent, emulsifier, suspending agent, etc. In the arctigenin injection preparation, each preparation unit contains 0.01-50 mg of arctigenin serving as a medicinal effective component.
The invention proves that the above preparations of the burdock have obvious therapeutic effect on spinal cord injury through specific embodiments, and the preparation is realized through the following embodiments:
example 7 the results of the behavioral assessment of the treatment effect of arctigenin on acute spinal cord injury show that all animals have complete paraplegia after the mice are modeled, and 5 days after modeling, the BMS scores of the arctigenin treatment group are all higher than those of the model group, and the scores of the arctigenin treatment group are gradually reduced according to the dosage, and the comparative differences among the groups are statistically different. The Catwalk is adopted to evaluate the exercise recovery condition of the mice, the steps per second, coordination and hind limb support force of the mice in the high-dose group of arctigenin are obviously increased compared with those of other three groups after 6 weeks of treatment, the difference has statistical significance, the arctigenin is beneficial to the recovery of the exercise function of the SCI mice, and the treatment effect is in a dose-dependent relationship; the electrophysiological detection result shows that the action potential amplitude of each treatment group of arctigenin is recovered after 6 weeks of operation, and statistical analysis shows that the difference has statistical significance, which prompts that arctigenin contributes to the recovery of the function of the descending conduction bundle of the spinal cord; nissel staining results show that arctigenin high-dose group mouse cells are densely arranged, a plurality of large neurons can be seen, cytoplasm staining is uniform, Nisshi bodies are rich, soma nuclei are clearly identified, and axons and dendrites can be easily identified. The arctigenin medium and low dose groups have large and medium-volume neurons, cytoplasm is uniformly dyed, Nisshi bodies are rich, and soma nuclei are clearly identified; the model group has scattered neuron arrangement, fresh large and medium size neurons, small cell bodies and fuzzy Neisseria.
Example 8 the results of the behavioral evaluation of the therapeutic effect of arctigenin on chronic compressive spinal cord injury indicate that 60 rats all exhibited different degrees of hind limb paralysis after chronic compressive spinal cord injury. The arctigenin treatment group has obvious recovery of motor function, and the comparison difference of the two groups has significant significance; the pathological examination result shows that the neurons at the anterior horn of the gray matter swell after the chronic compressive spinal cord injury, the nissl body is lost, the satellite phenomenon exists, the neuron phagocytosis phenomenon is obvious, a softening focus can be seen, and a small amount of microglia and astrocyte are proliferated. White matter is represented by irregular areas of flaky demyelination, glial cell proliferation, and vacuolar changes seen. Arctigenin can treat mild edema of spinal gray matter, neuron swelling, obvious proliferation of microglia and astrocytes and obvious proliferation of white matter glial cells, and pathological changes are relieved compared with those of a control group.
The arctigenin has exact treatment effect on the spinal cord injury, and compared with the existing treatment method of the spinal cord injury, the arctigenin has the following advantages:
1. the test results of example 7 and example 8 show that arctigenin can obviously restore action potential amplitude of animals with spinal cord injury and protect neurons, thereby restoring mobility of animals with spinal cord injury and providing a new idea for SCI treatment and function restoration.
2. Compared with operation and acupuncture treatment, the medicine has the advantages of convenient medication, less pain and the like, and can obviously improve sensation, movement, sphincter dysfunction and other complications caused by spinal cord injury. Effectively relieving the pain of the patient and improving the life quality.
3. The medicine has low toxic and side effects. The arctigenin is a natural traditional Chinese medicine monomer extracted from traditional Chinese medicine burdock, has low toxic and side effects on human bodies, can remarkably improve the medication safety and medication compliance of patients, and further greatly improves the treatment effect and life quality of patients with spinal cord injury.
Drawings
FIG. 1 behavioral scores of groups of mice with acute bone marrow injury
FIG. 2 electrophysiological detection of acute bone marrow injury in groups of mice
FIG. 3 Nissel staining of groups of mice with acute bone marrow injury
Detailed Description
The invention will now be further illustrated by the following specific examples, but it will be understood that the invention is not limited thereto in any way.
Example 1 arctigenin injection
Figure BDA0001260972580000031
The preparation process comprises the following steps: mixing propylene glycol and ethanol, adding arctigenin, stirring to dissolve, adding 0.9% sodium chloride solution, stirring, adding 0.5% activated carbon, stirring, removing carbon, and packaging.
Example 2 arctigenin injection
Figure BDA0001260972580000032
Figure BDA0001260972580000041
The preparation process comprises the following steps: mixing PEG-400 and ethanol, adding arctigenin, stirring to dissolve, adding 0.9% sodium chloride solution to 10L, stirring, adding 0.5% activated carbon for injection, stirring, removing carbon, and packaging.
Example 3 arctigenin injection
Arctiin 1g
Ethanol 3.3L
Adding water for injection to 10L
The preparation process comprises the following steps: adding arctigenin into ethanol, stirring for dissolving, adding water for injection to 10L, stirring, adding 0.5% activated carbon for injection, stirring, removing carbon, and packaging.
EXAMPLE 4 preparation of tablets
Figure BDA0001260972580000042
The preparation process comprises mixing arctigenin and adjuvants including microcrystalline cellulose and sodium carboxymethyl starch, adding appropriate amount of starch slurry to make soft mass, and sieving with 16 mesh sieve for granulating. Drying wet granules at 60 deg.C, sieving dry granules with 20 mesh sieve, grading, sieving to obtain fine powder, mixing with magnesium stearate, mixing with dry granules, and tabletting to obtain tablet of about 200 mg.
EXAMPLE 5 microemulsion concentrate
Figure BDA0001260972580000043
The preparation process comprises the following steps: weighing medium-chain fatty glyceride, polyoxyethylene castor oil EL-40, 1, 2-propylene glycol and absolute ethyl alcohol according to the formula amount, mixing and stirring uniformly, adding arctigenin for dissolving, or performing ultrasonic treatment to accelerate dissolving to obtain a clear concentrated solution, namely the arctigenin microemulsion concentrate. The microemulsion concentrate can be further diluted for injection or oral administration.
EXAMPLE 6 microemulsion concentrate
Figure BDA0001260972580000044
Figure BDA0001260972580000051
The preparation process comprises the following steps: weighing PEG-2-stearate, Tween-20, 1-hexanol and PEG3350 according to the formula amount, mixing, uniformly stirring, adding arctigenin for dissolving, or performing ultrasonic treatment to accelerate dissolving to obtain a clear concentrated solution, namely the arctigenin micro-emulsion concentrate. The microemulsion concentrate can be further diluted for injection or oral administration.
Example 7 therapeutic Effect of Arctiin on acute spinal cord injury
Test materials and methods
1.1 modeling and grouping
72 healthy 6-week-old female C57Bl/6 mice were anesthetized by intraperitoneal injection of a tribromoethanol mixture (13 μ l/g), and under a surgical microscope (Leica DM651, Germany) the spinal cord was approached in the lamina space and lifted in one piece (T10) to expose the spinal cord sufficiently to form a square window of about 2.0mm in diameter, revealing the dura mater. The mouse is fixed in a special clamping groove and placed in the spinal cord impact injury instrument, the mouse is struck according to the parameters of the spinal cord impact instrument with the weight of 10g and the height of 6.25mm, the spinal cord at the injury part is rapidly congested and edematous, the hind limb of the mouse shakes and twitches, the tail part swings, and the hind limb paralysis is successfully modeled. Mice successfully modeled were randomly divided into 4 groups of 12 mice each, 1mg/kg of arctigenin-treated group (group a), 0.5mg/kg of arctigenin-treated group (group B), 0.25mg/kg of arctigenin-treated group (group C), and model group (group D). And (5) after operation, putting under a warm light lamp for resuscitation. Mice were urinated 2 times daily until the micturition reflex was restored. A. B, C the composition is administered by intraperitoneal injection of arctigenin at dosage of 1, 0.5, 0.25mg/kg daily for 30min after operation for 14 days. At 24h and 6w after the administration, 6 mice were anesthetized for each group by the same method, and the spinal cord tissue of the injured segment was observed.
1.2 behavioral assessment
The recovery of mouse SCI was evaluated using BMS (BMS mouse scale) scoring rules and 2 observers skilled in scoring criteria scored mice at 1d, 3d, 5d, 7d, 2W, 3W, 4W, 5W, 6W post-modeling, respectively. And 2, scoring, independently observing and recording the scores without knowing the experimental process and grouping, and taking the mean value.
Meanwhile, the recovery condition of the mouse SCI is evaluated by adopting Catwalk automatic quantitative gait analysis (Catwalk XT 9.0 software, Noldus company), and the operation is carried out according to a reporting method. The mouse is trained to walk in a one-way full-length way for 5 times in a walking groove of a Catwalk system in a dark environment 1 week before operation every day so as to adapt to a test environment and a test process, and the test room is kept quiet in order to ensure that the mouse is not interfered by external factors. After 8 weeks, the groups are respectively placed in Catwalk system walking grooves, effective walking is recorded for 5 times in the same direction and full length of each group, Regular Index (RI), step number per second (Cadence) and hindfoot pressure (hindpaw pressure) of the gait rule are recorded, and statistical analysis is carried out by Catwalk automatic quantitative gait analysis software.
1.3 electrophysiological assays (MEPs)
And detecting the mice double lower limb tibialis anterior muscle MEPs at 6w before and after each group of rats by using a Key point desktop myoelectric evoked potential instrument. After the mouse is anesthetized in the abdominal cavity, the stimulating electrodes are embedded under the skin of the vertebral column area at the horizontal height of the upper limbs on the two sides, the positive electrode is arranged on the head side, the negative electrode is arranged on the tail side, and the distance is about 1 cm. The recording electrode is embedded in tibialis anterior muscle to record action evoked potential, the positive and negative distance of the recording electrode is about 0.5cm, and the reference electrode is embedded under abdominal skin between the stimulating electrode and the recording electrode.
1.4 Nissl staining
Frozen sections were treated with Nissl staining solution (genemed, Canada) and the procedure was followed strictly according to the protocol. The stained neuronal cell paste appeared pink to bluish-purple and was used to determine the density and structural distribution of neurons.
1.5 data processing
Analysis was performed using SPSS 19.0. Data are expressed as mean ± standard deviation, single-factor analysis of variance is adopted for comparison among groups, SNK test is adopted for pairwise comparison, and the value P of less than 0.05 has statistical significance.
2 results of the test
2.1 behavioral Observation
After the model of the mouse is built, all animals have the phenomenon of complete paraplegia, and the BMS score is 0 after the model is built. After 5d to 8 weeks, the motor functions of all spinal cord injury mouse groups are recovered to different degrees, BMS scores of all groups gradually rise until 6w after treatment, and the BMS score of the group A can reach about 6. From 5D after molding, the BMS scores of A, B, C groups are higher than those of the D group, the scores of A, B, C groups are gradually reduced, and the comparative differences among the groups are statistically different (P < 0.05). The Catwalk is adopted to evaluate the exercise recovery condition of the mice, the steps per second, coordination and hind limb support force of the mice in the group A are obviously increased compared with those of other three groups after 6 weeks of treatment, and the difference has statistical significance (P is less than 0.05), which indicates that arctigenin is beneficial to the recovery of the exercise function of SCI mice.
2.2 electrophysiological testing
The evoked potential detection in the operation shows that the MEPs of the rat double hind limb tibialis anterior muscle is changed into 0 immediately after the striking, which indicates that the model is successfully made. A, B, C groups of action potential amplitude is detected to be recovered after 6 weeks, and the group A recovers best, and the statistical analysis shows that the difference has statistical significance, which indicates that the arctigenin contributes to the recovery of the function of the descending conduction bundle of the spinal cord.
2.3 Nissel staining
SCI tissue was subjected to Nissl staining after 6 weeks of treatment, and the neuronal cell pulp appeared pink to bluish-purple after staining. The experimental result shows that the cells of the group A mice are densely arranged, a plurality of large neurons can be seen, cytoplasm staining is uniform, nissl bodies are rich, soma nuclei are clearly identified, and axons and dendrites can be easily identified. B. Group C has large and medium sized neurons, uniform cytoplasmic staining, abundant Neisseria, clear recognition of soma nucleus; the D group of neurons are scattered in arrangement, and have large and medium-sized neurons, small cell bodies and fuzzy Neisseria bodies.
Example 8 therapeutic Effect of Arctiin on Chronic compressive spinal cord injury
Test materials and methods
1.1 creation and grouping of animal models
60 Wistar rats with the body weight of 300-350g are not limited. Pentobarbital (40mg/kg), 2%, was injected intraperitoneally for anesthesia, and a conventional sterile drape was placed, a posterior median incision was made, the spinous process and a portion of the vertebral lamina of T13 was removed, and the dura mater was exposed. And (3) placing a posterior progressive compression device: a plastic screw with a diameter of 3mm and a thread pitch of 0.5mm is screwed into the T13 vertebral plate, and then the screw is exposed every 5 days and screwed into the T13 vertebral plate for 5-6 times with a screw diameter of 0.25 mm. The lateral X-ray film is taken up to 30 days, and the vertebral canal invasion rate is observed to reach 50 percent and about 1.5 mm. Making into a moderate chronic spinal cord compression model. The 60 rats were randomly divided into two groups, group a: in the treatment group (30) of chronic spinal cord injury plus 1mg/kg arctigenin, 30 minutes after model preparation is completed, arctigenin is injected into tail vein once; group B: in the group of simple chronic spinal cord injuries (30), isotonic saline with equal volume is injected intravenously. Taking materials 1, 3, 7, 14 and 28 days after the model is made, and detecting the apoptosis condition of the injured spinal cord cells, wherein each time phase point comprises 6 animals.
1.2 behavioural examination
Animals were weighed and behaviorally examined 1, 3, 7, 14, 28 days after chronic compressive spinal cord injury. (1) Modified Tarlov scores were used: 0 and 1, no autonomous movement, and only non-reflex movement of hip and knee joints; 2, movement of three main joints of hip, knee, ankle of limbs; 3 minutes, can actively support the heavy and uncoordinated gait; 4 minutes, coordinated gait of forelimbs and hindlimbs, movement of interphalangeal joints during walking; and 5, normal gait. (2) Inclined plate test: the animal was held on the tilt plate for 5 seconds without slipping down, measuring the ability to grip and maintain posture.
1.3 preparation of pathological specimens
After 1, 3, 7, 14 and 28 days after chronic compressive spinal cord injury respectively, 2% pentobarbital sodium (40mg/kg) is used for abdominal anesthesia, the right auricle is cut off after left ventricle intubation, 200ml of ice saline is quickly perfused, about 200ml of 4% paraformaldehyde is perfused after the effluent liquid is clear, and then a spinal cord specimen with the injured section as the center and the length of about 2 cm is cut off. Immediately fixed with 10% neutral formalin for 48-72 hours, embedded in paraffin, sectioned continuously, 4 μm thick, and HE stained and TUNEL, respectively.
1.4 statistical treatment
Data are expressed as mean ± standard deviation using t-test.
2 results of the test
2.1 behavioural examination
Different degrees of hind limb paralysis were observed in 60 rats after chronic compressive spinal cord injury. The arctigenin treatment groups were significantly restored in motor function, and the comparative differences between the two groups were significant (table 1, table 2).
TABLE 1 results of Tarlov scoring test after chronic spinal cord compression injury in rats
Figure BDA0001260972580000081
In comparison with the group B, # p﹤0.05
TABLE 2 inclined plate test results after chronic spinal cord compression injury in rats
Figure BDA0001260972580000082
In comparison with the group B, # p﹤0.05
2.2 pathological examination
After the chronic compressive spinal cord injury, the grey anterior horn neuron is swollen, the nissl body is lost, the satellite phenomenon is generated, the neuron phagocytosis phenomenon is obvious, a softening focus is seen, and a small amount of microglia and astrocyte are proliferated. White matter is represented by irregular areas of flaky demyelination, glial cell proliferation, and vacuolar changes seen. Arctigenin can treat mild edema of spinal gray matter, neuron swelling, obvious proliferation of microglia and astrocytes and obvious proliferation of white matter glial cells, and pathological changes are relieved compared with those of a control group.
Example 9 clinical therapeutic Effect observation of Arctiin on patients with lumbar disc herniation
Clinical data 50 typical patients with lumbar intervertebral disc protrusion, 26 men and 24 women, age 27-66 years; 32 cases of L4/5 and 18 cases of L5/S1; the protrusions are shifted to the left 27 and right 23. All patients were unilateral with a single gap and a single limb radiating pain.
Treatment protocol 50 patients were treated with arctigenin at a dose of 1mg/kg/d from the day of treatment, and the relief of the radiation pain in one limb of the patient was recorded at day 3, week 1 and month 3 of the treatment.
Results the patient treatment results are reported in table 3.
TABLE 3 treatment of unilateral limb radiopain caused by prolapse of lumbar intervertebral disc with arctigenin
Figure BDA0001260972580000091
The results in table 3 show that 10 patients are relieved on the 3 rd day of treatment, 48 patients are relieved on the 3 month treatment, wherein the pain symptoms of 45 patients completely disappear, and both the symptoms and the pain symptoms reach 90%.

Claims (10)

1. Use of arctigenin in preparing medicine for treating spinal cord injury is provided.
2. The use of claim 1, wherein the spinal cord injury is acute spinal cord injury or chronic compressive spinal cord injury.
3. The use of claim 2, wherein the chronic compressive spinal cord injury is a chronic injury resulting from disc-related disease, hyperosteogeny, or tumor compression.
4. The use according to claim 3, wherein the disc-related disorder is cervical spondylosis, thoracic dislocation of vertebrae, or lumbar disc herniation.
5. The use according to claim 1, wherein the arctigenin is administered in an amount of 0.01mg/kg/d to 10mg/kg/d in a human.
6. The use according to claim 1, wherein the arctigenin is an oral preparation or an injectable preparation thereof.
7. The use as claimed in claim 6, wherein the oral preparation of arctigenin is tablet, capsule, granule or oral microemulsion thereof.
8. The use of claim 6, wherein the injectable formulation comprises an injectable solution and an injectable microemulsion.
9. The use according to claim 8, wherein each preparation unit of the injection preparation contains 0.01mg to 50mg of arctigenin, which is a pharmaceutically effective ingredient.
10. The use of claim 8, wherein the pharmaceutically acceptable carrier in the injection solution can be one or more of water for injection, sodium chloride, sodium citrate, citric acid, glycerol, ethanol, propylene glycol, and PEG-400.
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102026651A (en) * 2008-02-29 2011-04-20 阿索尔达治疗公司 Method for achieving desired glial growth factor 2 plasma levels
CN103027905A (en) * 2011-09-28 2013-04-10 鲁南制药集团股份有限公司 Use of arctigenin in preparing drug for treating synovitis
CN103356477A (en) * 2012-04-05 2013-10-23 山东新时代药业有限公司 Arctigenin-containing subcutaneous injection and application thereof

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006121518A2 (en) * 2005-05-10 2006-11-16 Angiotech International Ag Electrical devices, anti-scarring agents, and therapeutic compositions

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102026651A (en) * 2008-02-29 2011-04-20 阿索尔达治疗公司 Method for achieving desired glial growth factor 2 plasma levels
CN103027905A (en) * 2011-09-28 2013-04-10 鲁南制药集团股份有限公司 Use of arctigenin in preparing drug for treating synovitis
CN103356477A (en) * 2012-04-05 2013-10-23 山东新时代药业有限公司 Arctigenin-containing subcutaneous injection and application thereof

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
Arctigenin Confers Neuroprotection Against Mechanical Trauma Injury in Human Neuroblastoma SH-SY5Y Cells by Regulating miRNA-16 and miRNA-199a Expression to Alleviate Inflammation;song jie;《journal of molecular neuroscience》;20161005;第60卷(第1期);第115-129页 *
Arctigenin Suppress Th17 Cells and Ameliorates Experimental Autoimmune Encephalomyelitis Through AMPK and PPAR-γ/ROR-γt Signaling;li wen;《molecular》;20161231(第53期);第5356-5366页 *
牛蒡子苷元对关节软骨细胞增殖及Ⅱ型胶原表达的影响;陈世宣;《上海中医药杂志》;20151231;第49卷(第7期);第69-71页 *
牛蒡子苷元注射液对SD大鼠急性毒性研究;刘松江;《中国药物警戒》;20150831;第12卷(第8期);第462-463页 *

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