CN113384605B - Medicament for treating infantile autism caused by hypoxic-ischemic brain injury and preparation method thereof - Google Patents
Medicament for treating infantile autism caused by hypoxic-ischemic brain injury and preparation method thereof Download PDFInfo
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- 208000029028 brain injury Diseases 0.000 title claims abstract description 27
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- 238000002360 preparation method Methods 0.000 title abstract description 10
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
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- A61K31/33—Heterocyclic compounds
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- A61K31/365—Lactones
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- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4415—Pyridoxine, i.e. Vitamin B6
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- A61P25/00—Drugs for disorders of the nervous system
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Abstract
The invention provides a medicament for treating infantile autism caused by hypoxic-ischemic brain injury and a preparation method thereof, wherein the medicament comprises the following raw materials in parts by weight: 20-50 parts of ganoderic acid derivatives, 18-45 parts of total triterpenoids of ganoderma lucidum, 26-30 parts of ligustrazine hydrochloride, 22-34 parts of bilobalide, 10-20 parts of aesculetin, 12-22 parts of luteoloside and 3-15 parts of pyridoxine.
Description
Technical Field
The invention relates to the field of medicine preparation, in particular to a medicament for treating infantile autism caused by hypoxic-ischemic brain injury and a preparation method thereof.
Background
Infantile autism children autism (children autism) is a subtype of extensive developmental disorder, the infantile autism is developed before 3 years old, and a disease which is mainly characterized by qualitative damage of social interaction capacity, language developmental disorder, behavior stereotypy, narrow interest and the like is caused, about 61% of autism patients in China have intellectual disorder through research and statistics, and most of autism individuals belong to the category of low function; in high functional autism, the test scores of the speech intelligence quotient (VIQ) and the operation intelligence quotient (PIQ) are lower than those of normal children, so that the overall cognitive ability and learning ability of the autism children are poor. The autism is caused mainly by genetic factors, abnormal immune function and brain organic injury, wherein the brain organic injury also comprises hypoxia and ischemic brain injury, the brain metabolism is the most vigorous due to energy failure, the oxygen consumption accounts for about half of the whole body, once hypoxia occurs, the brain tissue is subjected to intracellular edema, and the neuron excitotoxic injury is caused.
Aiming at the occurrence matrix of hypoxic and ischemic brain injury, the medicine is used for relieving or blocking brain cell energy failure and free radical injury, and the patent 'novel treatment medicine for ischemic brain injury' has patent number: CN112773805A, to prepare a composition that maintains the glutamic acid transporter GLT-1 on the astrocyte membrane and reduces the extracellular glutamic acid concentration during ischemic brain injury, but the functional efficacy on brain injury was not significant.
Disclosure of Invention
In view of the above, the present invention provides a drug for treating infantile autism caused by hypoxic-ischemic brain injury and a preparation method thereof, which solve the above problems.
The technical scheme of the invention is realized as follows: a medicament for treating infantile autism caused by hypoxic-ischemic brain injury comprises the following raw materials in parts by weight: 20-50 parts of ganoderic acid derivatives, 18-45 parts of total triterpenoids of ganoderma lucidum, 26-30 parts of ligustrazine hydrochloride, 22-34 parts of bilobalide, 10-20 parts of aesculetin, 12-22 parts of luteoloside and 3-15 parts of pyridoxine.
Preferably, the medicament for treating infantile autism caused by hypoxic-ischemic brain injury comprises the following raw materials in parts by weight: 30 parts of ganoderic acid derivatives, 35 parts of total triterpenes of ganoderma, 28 parts of ligustrazine hydrochloride, 28 parts of bilobalide, 15 parts of aesculetin, 17 parts of luteolin and 10 parts of pyridoxine.
Preferably, the preparation method of the medicament for treating infantile autism caused by hypoxic-ischemic brain injury comprises the following steps:
step (1): dissolving ligustrazine hydrochloride, bilobalide, aesculetin and luteolin in 85% ethanol by mass, mixing and stirring to obtain suspension;
step (2): dissolving ganoderic acid derivatives, total triterpenes of Ganoderma lucidum and pyridoxine in water, and stirring;
and (3): and (3) mixing the steps (1) and (2), adding 2-4 times of volume of water, mixing and stirring, carrying out micro-jet high-pressure homogenization, and circulating for 8-12 times to obtain the infantile autism rehabilitation medicament.
Preferably, the concentration of the suspension drug in the step (1) is 100-200 mg/mL.
Preferably, the stirring speed in the step (2) is 200-600 rpm, and the stirring time is 50-120 s.
Preferably, the volume ratio of the mass of the ganoderic acid derivatives, the total triterpenes of the ganoderma lucidum and the pyridoxine to the water in the step (2) is 1-3: 6-10.
Preferably, the pressure of the high-pressure homogenization of the microjet in the step (3) is 30000-33000 psi.
Compared with the prior art, the invention has the beneficial effects that:
the invention reasonably selects the raw materials of the medicine, has scientific proportioning, has obvious effect on infantile autism caused by hypoxic and ischemic brain injury, combines the raw materials, can promote the metabolism of glucose and amino acid in the brain, increase the blood flow of carotid artery, improve the blood flow of brain, adds the ganoderic acid derivative and the total triterpenoid of ganoderma lucidum to combine other raw materials to relieve the energy failure of brain cells, adds the brain metabolism by ligustrazine hydrochloride and bilobalide, plays a role in protecting the brain cells by penetrating through the blood brain barrier and preventing the damage of free radicals of the brain cells, and the aesculetin can antagonize the excitotoxicity action, obviously relieves the calcium overload in the brain cells, blocks the excitotoxicity action and the calcium ion inflow of the brain cells, and the luteolin repairs the excitation damage of neurons, has high selective inhibiting action on the moving area of the brain cortex, and the pyridoxine protects the vascular endothelial cells and reduces the damage of the activated platelets of the endothelial cells, the raw material medicines are scientifically matched and combined with a neurotrophic medicine which can provide special brain, act on central nerves in various modes, regulate and improve the metabolism of neurons, promote the formation of synapses, induce the differentiation of the neurons, and further protect nerve cells from being damaged by various ischemia and neurotoxins.
Detailed Description
In order to better understand the technical content of the invention, specific examples are provided below to further illustrate the invention.
The experimental methods used in the examples of the present invention are all conventional methods unless otherwise specified.
The materials, reagents and the like used in the examples of the present invention are commercially available unless otherwise specified.
Example 1
A medicament for treating infantile autism caused by hypoxic-ischemic brain injury comprises the following raw materials in parts by weight: 20 parts of ganoderic acid derivatives, 18 parts of total triterpenoids of ganoderma lucidum, 26 parts of ligustrazine hydrochloride, 22 parts of bilobalide, 10 parts of aesculetin, 12 parts of luteolin and 3 parts of pyridoxine.
Example 2
A medicament for treating infantile autism caused by hypoxic-ischemic brain injury comprises the following raw materials in parts by weight: 50 parts of ganoderic acid derivative, 45 parts of total triterpenes of ganoderma, 30 parts of ligustrazine hydrochloride, 34 parts of bilobalide, 20 parts of aesculetin, 22 parts of luteolin and 15 parts of pyridoxine.
Example 3
The medicament for treating infantile autism caused by hypoxic-ischemic brain injury comprises the following raw materials in parts by weight: 30 parts of ganoderic acid derivatives, 35 parts of total triterpenoids of ganoderma lucidum, 28 parts of ligustrazine hydrochloride, 28 parts of bilobalide, 15 parts of aesculetin, 17 parts of luteoloside and 10 parts of pyridoxine.
The raw materials of the embodiments 1-3 are prepared by the following preparation method:
step (1): dissolving ligustrazine hydrochloride, bilobalide, aesculetin and luteolin in 85% ethanol, mixing and stirring to obtain suspension with drug concentration of 150 mg/mL;
step (2): dissolving ganoderic acid derivatives, total triterpenes of ganoderma lucidum and pyridoxine in water, and stirring uniformly at the stirring speed of 400rpm for 100 s;
and (3): and (3) mixing the steps (1) and (2), adding water with the volume of 3 times, mixing and stirring, carrying out high-pressure homogenization by using micro-jet at the pressure of 32000psi, and circulating for 10 times to obtain the infantile autism rehabilitation medicament.
Example 4
A medicament for treating infantile autism caused by hypoxic-ischemic brain injury comprises the following raw materials in parts by weight: 20 parts of ganoderic acid derivatives, 18 parts of total triterpenoids of ganoderma lucidum, 26 parts of ligustrazine hydrochloride, 22 parts of bilobalide, 10 parts of aesculetin, 12 parts of luteolin and 3 parts of pyridoxine;
the preparation method comprises the following steps:
step (1): dissolving ligustrazine hydrochloride, bilobalide, aesculetin and luteolin in 85% ethanol, mixing and stirring to obtain suspension with drug concentration of 100 mg/mL;
step (2): dissolving ganoderic acid derivatives, total triterpenes of ganoderma lucidum and pyridoxine in water, and stirring uniformly at the stirring speed of 200rpm for 50 s;
and (3): and (3) mixing the steps (1) and (2), adding 2 times of water, mixing and stirring, carrying out high-pressure homogenization by using micro jet flow at the pressure of 30000psi, and circulating for 8 times to obtain the infantile autism rehabilitation medicament.
Example 5
A medicament for treating infantile autism caused by hypoxic-ischemic brain injury comprises the following raw materials in parts by weight: 50 parts of ganoderic acid derivative, 45 parts of total triterpenoids of ganoderma lucidum, 30 parts of ligustrazine hydrochloride, 34 parts of bilobalide, 20 parts of aesculetin, 22 parts of luteolin and 15 parts of pyridoxine;
the preparation method comprises the following steps:
step (1): dissolving ligustrazine hydrochloride, bilobalide, aesculetin and luteolin in 85% ethanol by mass, mixing and stirring to obtain suspension with drug concentration of 200 mg/mL;
step (2): dissolving ganoderic acid derivatives, total triterpenes of ganoderma lucidum and pyridoxine in water, and stirring uniformly at the stirring speed of 600rpm for 120 s;
and (3): and (3) mixing the steps (1) and (2), adding 4 times of water, mixing and stirring, carrying out high-pressure micro-jet homogenization under the pressure of 33000psi, and circulating for 12 times to obtain the infantile autism rehabilitation medicament.
First, experimental verification
(one) the agent of the present invention protects brain cells
1. The experimental method comprises the following steps: taking 6 groups of 15-day-old white mouse embryos, treating the 6 groups of white mouse embryos with 0.025% trypsin digestive fluid respectively, placing separated brain cells in a culture medium for culture, changing the culture medium into a serum-free culture medium after two days, adding glutamic acid into a cell culture dish, adding 0.9% physiological saline into 5 samples of an experimental group and 100 mu M of the medicament prepared in the embodiments 1-5 of the invention respectively, adding 0.9% physiological saline into a control group to test the protective effect of the medicament on the brain cells, evaluating the damage degree of the brain cells by determining the percentage of the amount of LDH (lactate dehydrogenase) released by the cells to the total amount of the LDH, and determining that the high concentration of the released LDH indicates that the damage degree of the cells is large;
2. the experimental results are as follows:
| lactate dehydrogenase Release Rate (%) | |
| Experimental group 1 | 39.4 |
| Experimental group 2 | 35.7 |
| Experimental group 3 | 32.9 |
| Experimental group 4 | 40.1 |
| Experimental group 5 | 42.3 |
| Control group | 68.9 |
The excessive glutamic acid can cause brain cells to be poisoned and damaged or die, and the experimental result of the invention shows that the prepared medicament has obvious effect of reducing the brain cell damage, wherein the example 3 is more obvious.
(II) protective action under cerebral ischemia and hypoxia state
1. The experimental method comprises the following steps: taking 18 7-day-old young mice, dividing 15 young mice into 5 experimental groups, dividing each group into 3 groups, using the remaining 3 mice as a control group, anesthetizing the experimental groups, stripping and ligating blood vessels of the right carotid artery, recovering the experimental groups through an operation, injecting 5mg/kg of the medicament in the embodiment 1-5 into the abdominal cavity of the experimental groups, injecting 0.9% physiological saline into the control group, placing the young mice in an atmosphere of 8% oxygen/92% nitrogen within 5min, causing an anoxic state at the temperature of 32 ℃ for 3 hours, then placing the young mice back to a normal living environment, anesthetizing 30 days later, removing the brains, dividing the brains into left and right halves after stripping off the cerebellum and the cerebral neck, weighing, and indicating that the damage degree of the brains is large by the weight loss percentage of the right half brains relative to the left half brains.
Percent weight loss ═ weight loss [ (weight left brain-weight right brain)/weight left brain ] x 100%
2. The experimental results are as follows:
the experimental results show that the medicine can prevent the brain from alleviating damage in the ischemia and hypoxia state and has obvious protective effect on the brain.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (7)
1. A medicament for treating hypoxic-ischemic brain injury, comprising: the feed is prepared from the following raw materials in parts by weight: 20-50 parts of ganoderic acid derivatives, 18-45 parts of total triterpenoids of ganoderma lucidum, 26-30 parts of ligustrazine hydrochloride, 22-34 parts of bilobalide, 10-20 parts of aesculetin, 12-22 parts of luteoloside and 3-15 parts of pyridoxine.
2. The agent for treating hypoxic-ischemic brain injury according to claim 1, wherein: the feed is prepared from the following raw materials in parts by weight: 30 parts of ganoderic acid derivatives, 35 parts of total triterpenes of ganoderma, 28 parts of ligustrazine hydrochloride, 28 parts of bilobalide, 15 parts of aesculetin, 17 parts of luteolin and 10 parts of pyridoxine.
3. The method for preparing a pharmaceutical composition for the treatment of hypoxic-ischemic brain injury according to claim 1, wherein the pharmaceutical composition comprises: the method comprises the following steps:
step (1): dissolving ligustrazine hydrochloride, bilobalide, aesculetin and luteolin in 85% ethanol by mass, mixing and stirring to obtain suspension;
step (2): dissolving ganoderic acid derivatives, total triterpenes of Ganoderma lucidum and pyridoxine in water, and stirring;
and (3): and (3) mixing the steps (1) and (2), adding 2-4 times of volume of water, mixing and stirring, carrying out high-pressure homogenization on the obtained product by using micro-jet, and circulating for 8-12 times to obtain the medicament for treating the hypoxic-ischemic brain injury.
4. The method for preparing a pharmaceutical agent for the treatment of hypoxic-ischemic brain injury according to claim 3, wherein: the concentration of the suspension medicine in the step (1) is 100-200 mg/mL.
5. The method for preparing a pharmaceutical agent for the treatment of hypoxic-ischemic brain injury according to claim 3, wherein: in the step (2), the stirring speed is 200-600 rpm, and the stirring time is 50-120 s.
6. The method for preparing a pharmaceutical agent for the treatment of hypoxic-ischemic brain injury according to claim 3, wherein: the volume ratio of the mass of the ganoderic acid derivatives, the total triterpenoids of the ganoderma lucidum and the pyridoxine to the water in the step (2) is 1-3: 6-10.
7. The method for preparing a pharmaceutical agent for the treatment of hypoxic-ischemic brain injury according to claim 3, wherein: and (4) carrying out high-pressure homogenization on the microjet in the step (3) at 30000-33000 psi.
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