CN119033899A - Traditional Chinese medicine composition, traditional Chinese medicine preparation and application thereof - Google Patents
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Abstract
The invention discloses a traditional Chinese medicine composition, a traditional Chinese medicine preparation and application thereof, and relates to the technical field of medicine production, wherein the traditional Chinese medicine composition comprises the following raw materials in parts by weight, 5-20 parts of ephedra; 5-30 parts of cassia twig, 1-10 parts of fish oil, 3-25 parts of Chinese angelica, 3-25 parts of szechuan lovage rhizome, 5-20 parts of peach seed, 5-20 parts of dangshen, 5-20 parts of ginger, 5-30 parts of honey-fried licorice root and 10-100 parts of gypsum. The traditional Chinese medicine composition has the characteristics of multiple targets, small toxic and side effects and the like, and plays roles in treating cerebral infarction mainly by improving hemorheology, inhibiting thrombosis, enhancing organism immunity, inhibiting activation of microglial cells in brain and damage of mature neurons, improving neuron apoptosis and the like.
Description
Technical Field
The invention relates to the technical field of medicine production, in particular to a traditional Chinese medicine composition, a traditional Chinese medicine preparation and application thereof.
Background
Cerebral infarction (Cerebral infarction, CI) is a major manifestation of ischemic stroke, which is caused by ischemic necrosis or softening of local brain tissue due to brain blood supply disorders, ischemia, hypoxia. The clinical common types of cerebral infarction are cerebral thrombosis, lacunar infarction, cerebral embolism and the like, and cerebral infarction accounts for 80% of all cerebral strokes. The clinical manifestations are mainly characterized by sudden fainting, unconsciousness, hemiplegia, speech disorder and intellectual disorder.
The western medicine has obvious advantages in the acute phase of treating cerebral apoplexy, and is clinically administered with thrombolysis, platelet aggregation resistance, anticoagulation, cerebral metabolism promotion, brain nerve nutrition and other symptomatic treatment treatments. Early thrombolytic therapy can obviously reduce sequelae and improve prognosis of patients, but thrombolytic therapy has stricter indication, short thrombolytic time window, most patients can not be delivered to hospitals in time, and the optimal period of thrombolysis is missed. 70% of the treated surviving patients remain with varying degrees of disability, placing a heavy burden on their families and society.
In addition, although the western medicines are clinically used for treating cerebral infarction, the western medicines have large side effects and poor effects, and can not fundamentally solve the etiology and have the effect of preventing cerebral infarction.
Disclosure of Invention
The invention mainly aims to provide a traditional Chinese medicine composition, a traditional Chinese medicine preparation and application thereof, and aims to solve the problems that the traditional Chinese medicine and western medicine in the prior art have large side effects and poor treatment effect and cannot prevent cerebral infarction.
In order to achieve the aim, the invention provides a traditional Chinese medicine composition which comprises the following raw materials in parts by weight:
5-20 parts of ephedra;
5-30 parts of cassia twig;
1-10 parts of fish oil;
5-25 parts of Chinese angelica;
5-25 parts of ligusticum wallichii;
5-20 parts of peach kernel;
5-20 parts of radix codonopsis;
5-20 parts of ginger;
5-30 parts of honey-fried licorice root and 10-100 parts of gypsum.
In an embodiment, the traditional Chinese medicine composition further comprises 1-10 parts of aconite root and 5-15 parts of pinellia tuber by weight.
In one embodiment, the traditional Chinese medicine composition comprises the following raw materials, by weight, 5-15 parts of ephedra;
5-15 parts of cassia twig;
2-5 parts of fish oil;
5-10 parts of Chinese angelica;
5-10 parts of ligusticum wallichii;
5-15 parts of peach kernel;
5-10 parts of radix codonopsis;
5-10 parts of ginger;
5-15 parts of honey-fried licorice root and 20-50 parts of gypsum.
In one embodiment, the Chinese medicinal composition comprises the following raw materials in parts by weight;
10 parts of cassia twig;
5 parts of fish oil;
9 parts of Chinese angelica;
9 parts of ligusticum wallichii;
10 parts of peach kernel;
9 parts of radix codonopsis;
9 parts of ginger;
9 parts of honey-fried licorice root;
30 parts of gypsum;
radix Aconiti lateralis Preparata 9 parts, and
9 Parts of pinellia ternate.
In one embodiment, the fish oil comprises EPA and DHA, and the sum of the masses of EPA and DHA is greater than or equal to 70% by mass of the fish oil.
In one embodiment, the aconite type comprises Heishuang tablet or rhizoma typhonii tablet, and/or,
The semen Persicae comprises processed semen Persicae, and/or,
The gypsum includes gypsum, and/or,
The rhizoma Pinelliae comprises purified rhizoma Pinelliae or rhizoma Pinelliae Preparata.
The invention also provides a traditional Chinese medicine preparation, which comprises the traditional Chinese medicine composition.
In one embodiment, the type of the Chinese medicinal preparation comprises mixture, soft extract, pill or capsule.
The invention also provides an application of the traditional Chinese medicine composition or the traditional Chinese medicine preparation in preparing an inhibitor for cerebral infarction.
In one embodiment, the cerebral infarction comprises an ischemic cerebral infarction.
The invention provides a traditional Chinese medicine composition, a traditional Chinese medicine preparation and application thereof, wherein the traditional Chinese medicine composition takes ephedra and cassia twig as monarch drugs, has the effects of opening striae and eliminating cold evil, is compatible with aconite and ginger, has the effects of tonifying fire and restoring yang, dispersing pathogenic wind and dredging channels and collaterals, has the effects of harmonizing ying and wei qi and blood, warming yang and dispersing qi, is compatible with ginger and peach kernel, has the effects of warming lung and relieving cough and treating phlegm and retained fluid, is compatible with angelica and pilose asiabell root and tonifying lung qi, nourishing blood and activating blood, and is compatible with pilose asiabell root and prepared licorice root, replenishing qi and invigorating spleen, promoting the production of body fluid and stomach, preventing sweating and strengthening healthy energy, gypsum property is cold, clearing heat and purging fire, restricting the warm nature of all medicines, preventing yin injury, is used as a counter-assistant, fish oil and Ligusticum wallichii can promote the circulation and remove blood stasis, and the medicines can ascend to the peak, is compatible with angelica and peach seed, has the effects of promoting blood circulation and removing blood stasis, dispelling wind and dredging collaterals to achieve the effects of 'blood circulation and dispelling wind and self-removing stasis', and the prepared licorice root can also harmonize the traditional Chinese medicine and the effects of the traditional Chinese medicine. The traditional Chinese medicine composition has the characteristics of multiple targets, small toxic and side effects and the like, and plays roles in treating cerebral infarction mainly by improving hemorheology, inhibiting thrombosis, enhancing organism immunity, inhibiting activation of microglial cells in brain and damage of mature neurons, improving neuron apoptosis and the like.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are required in the embodiments or the description of the prior art will be briefly described, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and other drawings may be obtained according to the structures shown in these drawings without inventive effort for a person skilled in the art.
Fig. 1 is a graph showing the result of scoring Zea Longa neurological symptoms of animal experiments using the traditional Chinese medicine compositions of example 1, example 2 and comparative example 1 provided by the present invention;
fig. 2 is a graph showing the results of the volume of cerebral infarction of the traditional Chinese medicine compositions of example 1, example 2 and comparative example 1 for animal experiments;
FIG. 3 is a graph showing the results of dyeing of 2,3, 5-triphenyltetrazolium chloride (TTC) used in animal experiments with the Chinese medicinal compositions of example 1, example 2 and comparative example 1;
fig. 4 is a graph showing the results of brain water content of the traditional Chinese medicine compositions of example 1, example 2 and comparative example 1 for animal experiments;
FIG. 5 is a graph showing the results of Activated Partial Thromboplastin Time (APTT) for animal experiments of the Chinese medicinal compositions of example 1, example 2 and comparative example 1 provided by the present invention;
FIG. 6 is a graph showing the Prothrombin Time (PT) results of the traditional Chinese medicine compositions of example 1, example 2 and comparative example 1 for animal experiments;
FIG. 7 is a graph showing the results of Thrombin Time (TT) for animal experiments of the traditional Chinese medicine compositions of example 1, example 2 and comparative example 1 provided by the present invention;
FIG. 8 is a graph showing the results of Fibrinogen (FIB) for animal experiments of the Chinese medicinal compositions of example 1, example 2 and comparative example 1 provided by the present invention;
FIG. 9 is a graph showing the results of anti-apoptosis factor Bcl-2 obtained by using the Chinese medicinal compositions of example 1, example 2 and comparative example 1 according to the present invention;
fig. 10 is a graph showing the results of pro-apoptotic factors Bax of the traditional Chinese medicine compositions of example 1, example 2 and comparative example 1 for animal experiments;
FIG. 11 is a graph showing the results of the pro-apoptosis factor Caspase-3 of the traditional Chinese medicine compositions of example 1, example 2 and comparative example 1 provided by the present invention for animal experiments;
FIG. 12 is a graph showing the results of the pro-apoptosis factor AIF of the traditional Chinese medicine compositions of example 1, example 2 and comparative example 1 provided by the present invention for animal experiments;
Fig. 13 is a graph showing results of the brain tissue hippocampal neuronal cells NeuN of the animal experiments using the traditional Chinese medicine compositions of example 1, example 2 and comparative example 1 provided by the present invention.
The achievement of the objects, functional features and advantages of the present invention will be further described with reference to the accompanying drawings, in conjunction with the embodiments.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention more clear, the technical solutions of the embodiments of the present invention will be clearly and completely described below. The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention. In addition, the meaning of "and/or" as it appears throughout includes three parallel schemes, for example "A and/or B", including the A scheme, or the B scheme, or the scheme where A and B are satisfied simultaneously. In addition, the technical solutions of the embodiments may be combined with each other, but it is necessary to base that the technical solutions can be realized by those skilled in the art, and when the technical solutions are contradictory or cannot be realized, the combination of the technical solutions should be regarded as not exist and not within the protection scope of the present invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Cerebral infarction (Cerebral infarction, CI) is a major manifestation of ischemic stroke, which is caused by ischemic necrosis or softening of local brain tissue due to brain blood supply disorders, ischemia, hypoxia. The clinical common types of cerebral infarction are cerebral thrombosis, lacunar infarction, cerebral embolism and the like, and cerebral infarction accounts for 80% of all cerebral strokes. The clinical manifestations are mainly characterized by sudden fainting, unconsciousness, hemiplegia, speech disorder and intellectual disorder. Cerebral infarction, which is a sudden brain disease, can occur at any age, most commonly in the middle aged and the elderly, who are 45-70 years old. The disease is relatively urgent, most of them have no precursor symptoms, the focal nerve signs reach peaks in several minutes to several hours, and most of them show complete apoplexy, clear consciousness or mild consciousness disturbance, the main embolism of internal carotid artery or middle cerebral artery causes large area cerebral infarction, serious cerebral edema, intracranial pressure increase, even cerebral hernia and coma, rare seizure, the embolism of vertebral basilar artery system often happens coma, and after the focal signs of individual cases are stable or once improved, aggravation prompt infarction recurrence or secondary hemorrhage and the like occur.
Cerebral infarction belongs to the category of traditional Chinese medicine 'stroke', and the traditional Chinese medicine considers that the etiology and pathogenesis of ischemic stroke are complex, mainly comprising external deficiency, fire, wind, phlegm, qi, blood and the like, namely, the cerebral infarction is closely related to internal injury and damage, improper diet, excessive body fat and phlegm, qi deficiency and evil and the like. The main causes of the cerebral blood supply are liver wind internal movement, cerebral blood supply insufficiency, blood circulation malformation, cerebral cell oxygen loss necrosis, meridian obstruction, venation obstruction, emotional depression, phlegm turbidity obstruction and clear orifices after cerebral concussion, blood stasis obstruction, coma dementia paralysis, limb incapacitation, memory loss or cataract eye blindness, headache, dizziness or coma, vascular sclerosis, hyperplasia calcification, plaque forming small thrombus, oxygen supply deficiency, hemiplegia, aphasia, dysphagia, consciousness disturbance and the like, and the internal artery can cause ipsilateral eye blindness, but the sequelae such as hemiplegia, dyskinesia, memory decline, gait abnormality, bedridden, life incapacity, muscular atrophy, joint stiffness deformation, foot inversion, foot eversion, walking wobble, finger incapacity and the like are caused by vascular diseases.
In western medicine theory, the coagulation function plays a key role in the pathogenesis of cerebral infarction. After the inner membrane of the vascular wall is damaged, the tangible components in the blood are easy to adhere and deposit, more coagulation factors are stimulated to be released, and the level of lipoprotein, cholesterol, fibrinogen and the like is increased due to abnormal glycolipid metabolism of a patient, so that the blood flow speed is comprehensively reduced, and the blood coagulation state is improved. Therefore, for cerebral infarction patients, improving the hypercoagulability of blood is significant for restoring cerebral blood flow perfusion, restoring cerebral blood oxygen supply, promoting the recovery of damaged nerve tissues, reducing the complication rate and having recovery curative effect on patients.
Currently, drugs for improving the hypercoagulability state of blood include aspirin and the like, and the therapeutic mechanism thereof is anti-platelet aggregation. However, 47% of aspirin patients have drug resistance, and adverse reactions such as gastrointestinal damage, liver and kidney function damage, coagulation function damage and the like can occur after long-term administration. Meanwhile, aspirin only has a certain effect of relieving and preventing recurrence after cerebral infarction is developed, and the aspirin is not beneficial to treatment and prevention of ischemic stroke, but rather remarkably increases the risk of hemorrhage, and has no obvious repairing effect on cerebral infarction tissues.
Therefore, although the current hemiplegia caused by cerebral infarction is mostly treated by western medicines, the western medicines have large side effects and poor effects, and can not fundamentally solve the cause of the disease and effectively prevent cerebral infarction.
In view of the above, the invention provides a traditional Chinese medicine composition, which comprises the following raw materials in parts by weight:
5-20 parts of ephedra;
5-30 parts of cassia twig;
1-10 parts of fish oil;
5-25 parts of Chinese angelica;
5-25 parts of ligusticum wallichii;
5-20 parts of peach kernel;
5-20 parts of radix codonopsis;
5-20 parts of ginger;
5-30 parts of honey-fried licorice root and
10-100 Parts of gypsum.
In the above formula, herba Ephedrae is the grass stem of herba Ephedrae (EPHEDRA SINICA STAPF), herba Equiseti hiemalis (Ephedra equisetina Bunge) or herba Ephedrae (EPHEDRA INTERMEDIA SCHRENK ex Mey.) of Ephedraceae, and has pungent and slightly bitter taste and mild nature. Enter lung and bladder meridians. Has effects of inducing sweat, dispelling cold, dispersing lung qi, relieving asthma, inducing diuresis and relieving swelling.
Ramulus Cinnamomi is Cinnamomum cassia (Cinnamomum CASSIA PRESL) or its dried twig, and has pungent and sweet taste and mild nature. It enters heart, lung and bladder meridians. Has effects of inducing sweat, relieving muscle, warming and activating meridian, supporting yang, activating qi-flowing, and calming the pulse.
Semen Persicae is dried mature seed of Prunus persica (Prunus persica) or Prunus davidiana (Prunus davidiana) belonging to Rosaceae.
Radix Angelicae sinensis is dry root of Angelica sinensis ANGELICA SINENSIS (Oliv.) Diels of Umbelliferae, and has sweet and pungent taste and mild nature. It enters liver, heart and spleen meridians. Has effects of replenishing blood, promoting blood circulation, regulating menstruation, relieving pain, and loosening bowel to relieve constipation.
Ligusticum wallichii is the dried rhizome of Ligusticum Chuanxiong Hort (Ligusticum sinense 'Chuan xiong') belonging to Umbelliferae, and is pungent and warm in nature. Enter liver, gallbladder and pericardium meridians. Has effects of promoting blood circulation, activating qi-flowing, dispelling pathogenic wind, and relieving pain.
Codonopsis pilosula is radix Codonopsis (Panax ginseng C.A. Mey.) belonging to Araliaceae, and has sweet taste, slightly bitter taste, and slightly warm nature. It enters spleen, lung, heart and kidney meridians. Has effects of invigorating primordial qi, recovering pulse, relieving depletion, invigorating spleen, benefiting lung, promoting salivation, nourishing blood, tranquilizing mind, and improving intelligence.
Ginger is the dried rhizome of ginger (Zingiber oj-jicinale Rosc.) belonging to the family Zingiberaceae, and is pungent in taste and hot in nature. It enters spleen, stomach, kidney, heart and lung meridians. Has effects in warming middle warmer, dispelling cold, restoring yang, dredging collaterals, warming lung, and resolving fluid retention.
The radix Glycyrrhizae Preparata is prepared by baking Glycyrrhrizae radix (Glycyrrhiza uralensis Fisch.) of Leguminosae with Mel, and has sweet taste and mild nature. It enters heart, lung, spleen and stomach meridians. Has effects of invigorating spleen, regulating stomach function, invigorating qi, and recovering pulse.
Gypsum is a kind of gypsum of sulfate mineral anhydrite family, and has sweet and pungent taste and strong cold property, and its academic name is Gypsum Fibrosum. Enter lung and stomach meridians. Has effects of clearing heat, purging pathogenic fire, relieving restlessness, and quenching thirst.
Fish oil is oil extracted from different kinds of fish, especially fish rich in Omega-3 fatty acid, and has sweet taste and mild nature. Has effects of promoting blood circulation and reducing blood lipid.
According to the technical scheme of the traditional Chinese medicine composition, ephedra and cassia twig are used as monarch drugs, striae is opened, cold evil is removed, aconite and ginger are matched, the traditional Chinese medicine composition has the effects of tonifying fire and restoring yang, dispersing wind-cold and dredging channels and collaterals, cassia twig has the effects of regulating ying-qi and blood, warming yang and transforming qi, and tonifying lung and relieving cough and treating phlegm and fluid retention, angelica and pilose asiabell root are matched, the traditional Chinese medicine composition has the effects of tonifying lung and qi, nourishing blood and activating blood, codonopsis pilosula and honey-fried licorice root are used for tonifying qi and spleen, promoting the production of body fluid and stomach, preventing sweat and damaging the body resistance, gypsum is cold, heat-clearing and purging pathogenic fire and restricting the warm nature of all medicines, so as to prevent yin injury, and is used for counter-assistance, fish oil and ligusticum chuanxiong can promote blood circulation and remove blood stasis, and ligusticum chuanxiong can ascend the head and the eyes, and lead all medicines to ascend to peak, and are matched with angelica and peach seed, so as to dispel wind and remove stasis, so as to achieve the effects of "blood circulation and self-extinguishing" by honey-fried licorice root and peach seed are blended, so as to jointly play the effects of dispelling wind and strengthening body resistance, warming and promoting qi, promoting qi and dispelling qi and removing blood stasis and protecting cerebral vessels. The traditional Chinese medicine composition has the characteristics of multiple targets, small toxic and side effects and the like, and plays roles in treating cerebral infarction mainly by improving hemorheology, inhibiting thrombosis, reducing blood fat, enhancing organism immunity, inhibiting activation of microglial cells in brain and injury of mature neurons, improving apoptosis of neurons and the like.
In some embodiments of the invention, the traditional Chinese medicine composition further comprises the following raw materials, by weight, 1-10 parts of aconite, and 5-15 parts of pinellia ternate.
Radix Aconiti lateralis Preparata is processed product of radix Aconiti lateralis Preparata (Aconitum carmichaelii Debx) of Ranunculaceae, has pungent and sweet taste, and is toxic. It enters heart, kidney and spleen meridians. Has effects of restoring yang, rescuing collapse, invigorating fire, supporting yang, dispelling cold and relieving pain.
Pinellia ternate is tuber of pinellia ternate PINELLIA TERNATA (thunder.) of Araceae, and has effects of eliminating dampness, resolving phlegm, lowering adverse qi, relieving vomiting, relieving distention and resolving hard mass.
In the technical scheme of the invention, aconite root, radix aconiti lateralis preparata, ying-wei, qi-blood and yang-warming and qi-transforming are combined with ginger, pinellia tuber and peach seed to have the effects of warming lung and relieving cough and treating phlegm-fluid retention. The radix Aconiti lateralis is preferably a processed radix Aconiti lateralis Preparata.
In some embodiments of the present invention, the traditional Chinese medicine composition comprises the following raw materials in parts by weight:
5-15 parts of ephedra;
5-15 parts of cassia twig;
2-5 parts of fish oil;
5-10 parts of Chinese angelica;
5-10 parts of ligusticum wallichii;
5-15 parts of peach kernel;
5-10 parts of radix codonopsis;
5-10 parts of ginger;
5-15 parts of honey-fried licorice root and
20-50 Parts of gypsum.
With the formula, the effect of treating cerebral infarction is better.
In some embodiments of the present invention, the traditional Chinese medicine composition comprises the following raw materials in parts by weight:
10 parts of ephedra;
10 parts of cassia twig;
5 parts of fish oil;
9 parts of Chinese angelica;
9 parts of ligusticum wallichii;
10 parts of peach kernel;
9 parts of radix codonopsis;
9 parts of ginger;
9 parts of honey-fried licorice root;
30 parts of gypsum;
radix Aconiti lateralis Preparata 9 parts, and
9 Parts of pinellia ternate.
Wherein, the ephedra herb and the cassia twig are monarch drugs, the fish oil, the hemlock parsley, the angelica, the aconite and the like are ministerial drugs, the peach seed, the dangshen, the ginger, the liquorice, the gypsum, the pinellia tuber and the like are ministerial drugs, and the formula has the best effect of preventing and treating cerebral infarction.
In some embodiments of the invention, the fish oil comprises EPA and DHA, the sum of the masses of EPA and DHA being greater than or equal to 70% by mass of the fish oil. Omega-3 unsaturated fatty acids in fish oil, such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and the like, have good application prospects in the aspect of preventing and treating various cardiovascular diseases. In the technical scheme of the invention, EPA can be used as A3-series Prostaglandin (PG) precursor substance, active substances such as PG inhibitor (PGI 3), thromboxane A3 (TXA 3) and the like are generated under the action of lipid/cyclooxygenase, the effects of inhibiting platelet aggregation and prolonging the bleeding time are exerted, and DHA can be involved in brain functions to prevent and treat cerebral infarction.
In some embodiments of the invention, the aconite type comprises a black cis piece or a white aconite piece.
Wherein, heishun tablet is one of the products obtained by specially processing radix Aconiti lateralis, and other adjuvants such as vinegar, wine, glycyrrhrizae radix, and semen Sojae Atricolor are added during processing to make its color black or dark brown. The medicine effect of the Heixing tablet is stronger. Rhizoma typhonii is another common prepared aconite root product, more impurities and toxic components are removed in the processing process, and the rhizoma typhonii is lighter in color and is nearly white or light yellow. The rhizoma typhonii has deeper processing degree, weakened toxicity and easy decoction.
In some embodiments of the invention, the peach kernel comprises a processed peach kernel. The prepared peach kernel is a processed form of Chinese medicinal peach kernel, and the boiled peach kernel is easier to digest and absorb. For instance, it is often used to activate blood and resolve stasis, moisten intestines and relieve constipation.
In some embodiments of the invention, the gypsum comprises gypsum. Compared with other products, such as calcined gypsum (the main component of the calcined gypsum is anhydrous calcium sulfate), the main component of the gypsum is calcium sulfate dihydrate, has the effects of enhancing heat and toxic materials clearing, and promoting the production of body fluid to quench thirst, and is more suitable for cerebral infarction symptoms.
In some embodiments of the invention, the pinellia ternate comprises purified pinellia ternate or processed pinellia ternate. The purified pinellia tuber is prepared by cleaning fresh tuber of pinellia tuber, soaking in clear water and replacing water for several times until its taste becomes light, and the processed pinellia tuber is processed by specific processing method, usually including processing with lime water or Glycyrrhrizae radix.
The invention also provides a traditional Chinese medicine preparation, which comprises the traditional Chinese medicine composition.
The traditional Chinese medicine preparation comprises all technical schemes of the pharmaceutical composition, so that the traditional Chinese medicine preparation has all beneficial effects brought by the schemes, and is not described in detail herein.
In some embodiments of the invention, the type of the Chinese medicinal preparation comprises a mixture, a soft extract, a pill or a capsule. The type of the traditional Chinese medicine preparation can be changed according to specific use situations so as to achieve the optimal treatment effect.
The invention also provides an application of the traditional Chinese medicine composition or the traditional Chinese medicine preparation in preparing an inhibitor for cerebral infarction.
The application includes all technical solutions of the pharmaceutical composition, so that all the beneficial effects brought by the above solutions are also provided, and are not described in detail herein.
In some embodiments of the invention, the cerebral infarction comprises an ischemic cerebral infarction. The traditional Chinese medicine composition or the traditional Chinese medicine preparation can obviously improve and reduce the dead volume of cerebral infarction and the water content of brain of a model animal, and improve cerebral edema and blood coagulation function, so that the phenomenon of unsmooth blood circulation can be regulated and necrotic brain tissue can be repaired, and therefore, the traditional Chinese medicine composition or the traditional Chinese medicine preparation can be used for preventing and treating ischemic cerebral infarction, namely ischemic stroke.
The following technical solutions of the present invention will be described in further detail with reference to specific examples and drawings, and it should be understood that the following examples are only for explaining the present invention and are not intended to limit the present invention.
Example 1
A traditional Chinese medicine composition comprising:
10g of ephedra herb, 10g of cassia twig, 2g of fish oil, 10g of peach kernel, 6g of honey-fried licorice root, 9g of Chinese angelica, 9g of szechuan lovage rhizome, 9g of pilose asiabell root, 9g of ginger and 10g of gypsum.
Example 2
A traditional Chinese medicine composition comprising:
10g of ephedra herb, 10g of cassia twig, 5g of fish oil, 10g of peach kernel, 9g of honey-fried licorice root, 9g of angelica, 9g of szechuan lovage rhizome, 9g of dangshen, 9g of ginger, 9g of aconite, 20g of gypsum and 9g of pinellia tuber.
Comparative example 1
A traditional Chinese medicine composition comprising:
10g of ephedra herb, 10g of cassia twig, 10g of peach seed, 6g of honey-fried licorice root, 3g of Chinese angelica, 3g of szechuan lovage rhizome and 5g of gypsum.
Performance testing
The traditional Chinese medicine composition is prepared by respectively weighing ephedra, cassia twig, angelica sinensis, ligusticum wallichii, peach kernel, radix codonopsis pilosulae, ginger, honey-fried licorice root, gypsum, aconite and pinellia tuber in the embodiment 1-2 and the comparative example 1 according to the corresponding proportion, adding 8 times of water, soaking for 30-40 min, boiling with strong fire, decocting with slow fire for 30min, filtering the liquid medicine with a 200-mesh filter screen, and performing secondary decoction in the same way. Concentrating the decoction liquid of the two times into an extract, adding fish oil according to the corresponding proportion, and uniformly stirring to obtain 3 groups of traditional Chinese medicine compositions.
The medicine group is prepared by respectively taking 3 groups of the traditional Chinese medicine compositions and preparing the medicine liquid with the concentration of 1g/mL by pure water.
Grouping, modeling and administration of animals:
1. The adaptation period is 100 SPF-class male SD rats, 6-7 weeks old, and the weight (250+ -20 g) provided by Hunan Srilickida laboratory animal Co. The license number of the experimental animal production is SCXK (Hunan) 2019-0004 (validity period to 2024, month 05, day), which is issued by Hunan province science and technology agency. The adaptation period of the experimental rats was observed for 7d, and the experimental rats were allowed to enter the formal experimental period after no abnormality.
2. The middle cerebral artery occlusion (middle cerebral artery occlusion, MCAO) is the most commonly used model of focal cerebral ischemia (ischemic stroke/cerebral infarction) at present, and the MCAO model firstly blocks the External Carotid Artery (ECA) and branches thereof and blocks the pterygopalatine artery (PPA) so as to cut off the lateral side circulation blood flow from the extracranial source. A nylon wire is inserted from ECA, and blood supply at the position of the Middle Cerebral Artery (MCA) is blocked mechanically from being fed through the Internal Carotid Artery (ICA) to the Anterior Cerebral Artery (ACA) to build a middle cerebral artery ischemia model. The model can pull out nylon wires under the non-anesthesia state, restore blood flow and realize reperfusion. The line embolism method has the advantages of no craniotomy, definite effect and accurate control of ischemia and reperfusion time, is used for researching sensitivity and tolerance of neurons to ischemia, has ideal observation of drug curative effect, reperfusion damage and treatment time window, has the characteristics of small influence on the whole body and long animal survival time, and is suitable for researching chronic brain injury. The variable factors are well controlled, and the instability of the experimental result can be avoided.
15 Cases were randomly selected as a sham-surgery group, the remaining 85 cases were used for MCAO molding, fish wires were inserted into ICA middle arteries, scoring was performed by referring to the score 5 method Zea Longa after model preparation, and animals were rated 1-3 for the first time, and were considered successful in molding. At least 60 molded animals were selected and then grouped into model groups of at least 15 animals for each group, comparative example 1, example 2, and example 3.
TABLE 1Zea Longa neurological symptom score table
| Score value | Symptoms of neurological function |
| 0 | No symptom of neurological deficit |
| 1 | Mild focal neurological deficit, i.e. inability to extend the left forepaw by lifting the tail in the air |
| 2 | Moderate focal neurological deficit, i.e. left turn around |
| 3 | Moderate focal neurological deficit, i.e. difficulty in walking, leaning sideways to the left |
3. And (3) performing gastric lavage administration on each group of animals after molding and grouping, wherein the administration volume is 10mL/kg, the administration is performed once a day for 14 days, the blank group and the model control group are administered with pure water with equal volumes, and the drug group is administered according to the set dose.
4. Index determination and final treatment Zea Longa scores were performed before and on day 14 of administration. Animals were euthanized by post-anesthesia abdominal aortic blood sampling sacrifice after scoring of the functional symptoms on day 14 of dosing, serum was isolated after blood sampling and divided into 2 parts, one for determining four items of clotting, i.e., prothrombin Time (PT), activated Partial Thromboplastin Time (APTT), thrombin Time (TT), fibrinogen (FIB), and one for subsequent testing at-80 ℃. And after the last treatment, taking 7 animal brain tissues of each group for measuring the volume percent of cerebral infarction and the water content percent of brain, and taking partial brain tissues of the rest animals of each group for homogenizing and then for detecting the expression level of apoptosis-related factors Bcl-2, bax, caspase-3, AIF and NeuN proteins.
The brain infarction volume percentage measuring method comprises the steps of placing rat brain tissues in a glass dish, cutting the rat brain tissues into 5 pieces by a blade, cutting the rat brain tissues into pieces every 2mm, taking out and photographing the brain slices after the brain slices are placed in a 10% formaldehyde solution for 24 hours in a dark place, analyzing the brain infarction area by using Image J Image analysis software, wherein the normal part is red, the infarction area is white, calculating the volume of the brain infarction according to a volume calculation formula, and calculating the influence of brain swelling and individual differences on experimental results, wherein the brain slices are placed in the glass dish containing 1% TTC solution, covered with tinfoil paper, placed in a 37 ℃ constant temperature incubator for 20 minutes in dark place, turned over once at 10 minutes, carefully and gently contacted with staining solution, and the brain slices are taken out and photographed after TTC staining, and the brain infarction area is calculated according to the volume calculation formula, and the result is expressed by the volume ratio of the brain infarction is calculated according to the following formula:
infarct volume: v= (a1+a2+ & An.) t/2
Note that t is the slice thickness, A1 and A2 represent the ratio of the infarct volume of the area of the infarct of the mouth and tail of the block, respectively =infarct volume/hemispheric volume of the same side of the brain ×100%
The method for measuring the percentage of the water content of the brain comprises weighing the brain immediately, namely, the wet weight of the brain, carrying out TTC (time to temperature) dyeing, putting brain slices into a glass dish filled with tinfoil paper, drying in an oven until the weight is constant, namely, the weight of the brain stem, and carrying out calculation and statistics according to the following formula:
Brain moisture = (brain wet weight-brain dry weight)/brain wet weight×100%
5. Data processing, namely, carrying out statistical analysis on data by using SPSS17.0 statistical software after being processed by ECGAUTO software, wherein each group of measured data is expressed by x- +/-sem, each test group adopts a Student-T test (paired T test) to carry out comparison statistics with the data before administration, and carrying out inter-group variance analysis (F-test) before each test group carries out inter-group comparison, and carrying out statistical analysis by adopting a Student-T test (unpaired T test) when the inter-group variances are uniform and carrying out statistical analysis by adopting a corrected Student-T test when the inter-group variances are not uniform.
Experimental results
1. Scoring of the nervous function of groups of rats Zea Longa before and after treatment
As can be seen from fig. 1, the model group Zea Longa score significantly increased (P < 0.01) compared to the blank group, and there was no significant change before and after treatment (P > 0.05), indicating that MCAO rats were successfully modeled and the disease model was stable. The results after 14 days of administration show that the comparative example 1, the example 1 and the example 2 have significant differences (P < 0.05) compared with the model group, can significantly improve the neuro-behavioural of the MCAO rats, wherein the statistical differences of the example 2 are most significant, and initially show that the example 1 and the example 2 have good treatment effects on cerebral infarction rats.
In fig. 1, # indicates that the blank group has a very significant difference (P < 0.01) compared to the model group, and # indicates that the model group has a significant difference (P < 0.05).
2. Results of cerebral infarct volume in rats of each group
As shown in figures 2 and 3, TTC staining shows that the brain tissue of the rats in the blank group is normally stained without abnormal necrosis, the brain tissue of the rats in the model group is seriously necrotized, the infarct area of the brain tissue is large (white area), and compared with the model group, the comparative example 1 has no obvious difference, so that the treatment effect on the cerebral infarction is not obvious. The embodiment 1 and the embodiment 2 have certain treatment effects on cerebral infarction rats, wherein the treatment effect of the embodiment 2 is most remarkable, the TTC dyeing infarct area is obviously reduced, the brain tissue necrosis of rats can be effectively improved, and the cerebral tissue can be well protected. The prescription of the example 2 is scientific and effective, and the treatment effect is obvious.
In fig. 2, # indicates that the blank group has a very significant difference (P < 0.01) compared to the model group, and # indicates that the model group has a significant difference (P < 0.05).
3. Water content of brain tissue of rats of each group
The water content of the rat brain tissue in different groups is measured, and the result is shown in figure 4, wherein after modeling, the water content of the rat in the model group is found to be obviously increased (P is less than 0.01), the brain edema phenomenon appears, the rat brain tissue in the model group shows pathological damage, the brain water amount shows a descending trend after being treated by the traditional Chinese medicine composition, the brain edema state of the rat with brain peduncles is relieved to a certain extent after being treated by the traditional Chinese medicine composition, compared with the model group, the rat with brain peduncles in the example 1 and the example 2 have obvious differences, the statistical difference in the example 2 is most obvious, and the rat with brain peduncles has good treatment effect on the brain edema caused by the brain peduncles and has a certain protection effect on the brain tissue.
In fig. 4, # indicates that the blank group had very significant differences (P < 0.01) compared to the model group, and # indicates that the model group had very significant differences (P < 0.01).
4. Four-item measurement of coagulation of rats in each group
The results are shown in the graph 5, the graph 6, the graph 7 and the graph 8, compared with a blank group, the PT, APTT and TT contents in the blood of a model group are obviously reduced, the FIB content is obviously increased, the blood coagulation and thrombus of the MCAO rat are shown, the cerebral blood flow is blocked, the cerebral ischemia is caused, the blood coagulation index can be improved to different degrees after the treatment of a traditional Chinese medicine group, the good regulation effect of traditional Chinese medicine on the unsmooth blood circulation caused by cerebral infarction is shown, compared with the model group, the PT, APTT and FIB contents in the embodiment 1 and the embodiment 2 are obviously increased, the FIB content is obviously reduced, the blood coagulation and thrombus which appear after cerebral infarction can be effectively treated, the cardiac and cerebral blood circulation is regulated, and the effects of activating blood circulation to remove blood stasis and promoting qi and replenishing blood are exerted.
In fig. 5 to 8, # indicates that the blank group has a very significant difference (P < 0.01) from the model group, and # indicates that the blank group has a significant difference (P < 0.05) from the model group.
5. Cell necrosis and apoptosis-related factor expression in brain tissue of each group
The results of measuring the levels of cell necrosis and apoptosis-related factors in brain tissues of different groups of rats are shown in fig. 9, 10, 11 and 12: compared with a blank group, the anti-apoptosis factors Bcl-2 in the model group are obviously reduced, pro-apoptosis factors Bax, caspase-3 and AIF are obviously increased, which indicates that brain tissue apoptosis of a cerebral infarction rat is aggravated, so that the cerebral infarction degree is deepened, the infarcted tissues cannot be normally repaired, after treatment by a traditional Chinese medicine group, the comparative example 1 has the expression trend of adjusting the apoptosis related factors Bcl-2, bax, caspase-3 and AIF, the examples 1 and 2 can obviously increase Bcl-2, reduce the contents of Bax, caspase-3 and AIF, wherein the effect of the example 2 is most obvious, which indicates that the anti-apoptosis factors Bax, caspase-3 and AIF can effectively inhibit the apoptosis and necrosis process of brain tissue, promote the restoration of necrotic brain tissue of the cerebral infarction rat, have good restoration effect on necrotic brain tissue of the cerebral infarction rat and can effectively protect tissue.
In fig. 9 to 12, # indicates that the blank group has a very significant difference (P < 0.01) from the model group, and # indicates that the blank group has a significant difference (P < 0.05) from the model group.
6. Brain tissue hippocampal neuronal cell-NeuN expression in groups of rats
Cerebral infarction is followed by brain tissue death and focal neuronal damage. The neuronal nucleus (NeuN) is a neuronal specific nucleoprotein, expressed predominantly in mature neurons, and can serve as a reliable marker of mature neurons. Based on the above study, the effect of the drug on the neuron cells is further examined by immunohistochemical measurement of NeuN expression, and the result is shown in figure 13, wherein compared with a blank group, the NeuN expression level of the hippocampus of a rat in a model group is obviously reduced, which indicates that a cerebral infarction rat has obvious nerve cell necrosis or nerve injury, compared with a model group, the NeuN expression level of comparative example 1 has a trend of increasing the NeuN expression level, but no statistical difference, and the NeuN expression levels in examples 1 and 2 are obviously increased, wherein the most obvious effect of example 2 indicates that the NeuN expression level can effectively recover the neuron injury in the brain and repair the necrotic nerve cells and brain tissues, thereby effectively relieving cerebral infarction symptoms.
In fig. 13, # indicates that there was a very significant difference (P < 0.01) compared to the blank group, a significant difference (P < 0.05) compared to the model group, and # indicates that there was a very significant difference (P < 0.01) compared to the model group.
In conclusion, the traditional Chinese medicine composition provided by the invention has a good treatment effect on a rat cerebral infarction (ischemic cerebral infarction) model caused by an MCAO method (1) obviously reduces the pathological behavior score of a model rat in neuro-behavioural, improves the physiological state of the rat, has a good treatment effect, (2) has TTC staining, obviously reduces the cerebral infarction volume of the model rat, obviously reduces the cerebral water content of the model rat, improves the cerebral edema of the model rat, (3) obviously improves the coagulation index, shows that the traditional Chinese medicine composition has a good regulation effect on the blood operation disorder caused by cerebral infarction, and (4) can regulate the expression of apoptosis factors Bcl-2, bax, caspase-3 and AIF, has a good repair effect on necrotic brain tissues of the cerebral infarction rat, can effectively protect tissues, and (5) has the effects of effectively recovering neuronal damage in the brain, repairing necrotic nerve cells and brain tissues, and further improving the nerve functions, thereby effectively relieving cerebral infarction symptoms.
The foregoing is merely a preferred embodiment of the present invention and is not intended to limit the scope of the present invention, but various modifications and variations will be apparent to those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the scope of the present invention.
Claims (10)
1. The traditional Chinese medicine composition is characterized by comprising the following raw materials in parts by weight:
5-20 parts of ephedra;
5-30 parts of cassia twig;
1-10 parts of fish oil;
5-25 parts of Chinese angelica;
5-25 parts of ligusticum wallichii;
5-20 parts of peach kernel;
5-20 parts of radix codonopsis;
5-20 parts of ginger;
5-30 parts of honey-fried licorice root and
10-100 Parts of gypsum.
2. The traditional Chinese medicine composition according to claim 1, further comprising the following raw materials in parts by weight:
1-10 parts of aconite root, 5-15 parts of pinellia tuber.
3. The traditional Chinese medicine composition according to claim 1, wherein the traditional Chinese medicine composition comprises the following raw materials in parts by weight:
5-15 parts of ephedra;
5-15 parts of cassia twig;
2-5 parts of fish oil;
5-10 parts of Chinese angelica;
5-10 parts of ligusticum wallichii;
5-15 parts of peach kernel;
5-10 parts of radix codonopsis;
5-10 parts of ginger;
5-15 parts of honey-fried licorice root and
20-50 Parts of gypsum.
4. The traditional Chinese medicine composition according to claim 2, wherein the traditional Chinese medicine composition comprises the following raw materials in parts by weight:
10 parts of ephedra;
10 parts of cassia twig;
5 parts of fish oil;
9 parts of Chinese angelica;
9 parts of ligusticum wallichii;
10 parts of peach kernel;
9 parts of radix codonopsis;
9 parts of ginger;
9 parts of honey-fried licorice root;
30 parts of gypsum;
radix Aconiti lateralis Preparata 9 parts, and
9 Parts of pinellia ternate.
5. The traditional Chinese medicine composition according to claim 1, wherein the fish oil comprises EPA and DHA, and the sum of the masses of EPA and DHA is more than or equal to 70% by mass in the fish oil.
6. The composition of claim 2, wherein the aconite type comprises Heishuang tablet or Baifu tablet, and/or,
The semen Persicae comprises processed semen Persicae, and/or,
The gypsum includes gypsum, and/or,
The rhizoma Pinelliae comprises purified rhizoma Pinelliae or rhizoma Pinelliae Preparata.
7. A Chinese medicinal preparation comprising the Chinese medicinal composition according to any one of claims 1 to 6.
8. The traditional Chinese medicine preparation according to claim 7, wherein the type of the traditional Chinese medicine preparation comprises mixture, soft extract, pill or capsule.
9. Use of a traditional Chinese medicine composition according to any one of claims 1 to 6 or a traditional Chinese medicine preparation according to any one of claims 7 to 8 for the preparation of an inhibitor of cerebral infarction.
10. The use of claim 9, wherein the cerebral infarction comprises an ischemic cerebral infarction.
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Citations (2)
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| CN107596284A (en) * | 2016-07-11 | 2018-01-19 | 王涛 | A kind of Chinese medicine preparation of inrigorating qi and promoting blood circulation |
| CN109481641A (en) * | 2017-09-12 | 2019-03-19 | 张锦秀 | For treating the decoction of medicinal ingredients of apoplexy |
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|---|---|---|---|---|
| CN107596284A (en) * | 2016-07-11 | 2018-01-19 | 王涛 | A kind of Chinese medicine preparation of inrigorating qi and promoting blood circulation |
| CN109481641A (en) * | 2017-09-12 | 2019-03-19 | 张锦秀 | For treating the decoction of medicinal ingredients of apoplexy |
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