A combination drug for rapidly relieving acute stage orifice blockage in cerebral infarction and preparation method thereof

Abstract

The present invention relates to the technical field of cerebral infarction drugs, and specifically discloses a combination drug for rapidly relieving acute stage orifice blockage of cerebral infarction and a preparation method thereof, comprising the following raw materials by weight: 2g of bezoar, 1g of borneol and 10g of calamus. The present invention synthesizes bezoar, borneol and calamus according to specific weight arrays to form a drug, and the raw materials interact with each other, thereby achieving the effect of rapidly relieving the clinical symptoms of neurological deficit in the acute stage or even the ultra-early stage of cerebral infarction patients. The combination drug of the present invention has significant advantages in the speed and degree of symptom relief. At the same time, natural Chinese medicine ingredients are used, and the side effects are relatively small. Patients are not prone to serious adverse reactions during the course of taking the drug, which reduces the treatment risk and is more suitable for long-term use. The drug raw materials are relatively common and low in cost, and the preparation process is simple, which can reduce the treatment cost of the patient, facilitate promotion and application, and can effectively reduce the economic burden of the patient and his family.

Description

Technical Field

[0001] The invention belongs to the technical field of cerebral infarction drugs, and particularly relates to a combination drug for rapidly relieving acute stage orifice blockage of cerebral infarction and a preparation method thereof. Background Art

[0002] Ischemic stroke, also known as cerebral infarction, is a cerebrovascular disease that seriously threatens human health. It is characterized by high morbidity, high mortality, high disability rate and high recurrence rate. It has caused a heavy disease burden worldwide. After the onset of the disease, it often causes patients to suffer from sudden focal or diffuse neurological deficits, such as impaired consciousness, hemiplegia, hemisensory disorder, aphasia, ataxia, etc., which seriously affect the quality of life of patients and bring great physical and mental pain and economic pressure to patients and their families.

[0003] Acute vascular recanalization therapy is currently recognized by the industry as an important treatment method, including thrombolytic therapy and mechanical thrombectomy. In addition to vascular recanalization therapy, the effects of other drug treatments in the acute phase are also unsatisfactory. Although there are a variety of drugs used for the acute treatment of ischemic stroke, such as antiplatelet drugs, neuroprotective agents, etc., the efficacy of these drugs is limited and it is difficult to achieve satisfactory treatment results.

[0004] The pathogenesis of ischemic stroke is complex, among which ischemia and reperfusion injury is one of the important links leading to brain tissue damage. In this process, the structure of the blood-brain barrier (BBB) ​​is destroyed, and brain microvascular endothelial cells (BMECs) and their relationship with tight junctions play a decisive role in the degree of repair after BBB damage. The destruction of BBB causes the imbalance of the internal environment of brain tissue, aggravates the damage and death of neurons, and further affects the patient's neurological function recovery and prognosis. Therefore, protecting and repairing the BBB structure is of great significance for improving the prognosis of patients with ischemic stroke.

[0005] However, there is a relative lack of effective treatments and drugs for the ultra-early stage of ischemic stroke in clinical practice, and new treatment strategies and drugs are urgently needed to meet clinical needs. Summary of the invention

[0006] The object of the present invention is to provide a combination drug for rapidly relieving acute stage orifice blockage of cerebral infarction and a preparation method thereof, so as to solve the problems raised in the above-mentioned background technology.

[0007] To achieve the above object, the present invention provides the following technical solutions:

[0008] A combination medicine for rapidly relieving orifice blockage in the acute stage of cerebral infarction comprises 2g of bezoar, 1g of borneol and 10g of calamus, wherein the weight ratio of bezoar, borneol and calamus is 2:1:10.

[0009] A method for preparing a combined drug for rapidly relieving acute stage orifice blockage in cerebral infarction comprises the following preparation steps:

[0010] S1. Pretreatment of medicinal materials

[0011] Material selection: Select high-quality bezoar, borneol and calamus, and wash the bezoar and calamus separately. Then add purified water to the glass container containing the medicinal materials, completely immerse the bezoar and calamus medicinal materials, and extend the soaking time to 12-15 hours, stirring every 3-4 hours;

[0012] S2. Boil

[0013] Choose a ceramic casserole with a smooth inner wall and no cracks, with a capacity of 2-3 liters. Pour the soaked herbs and water into the casserole. First, quickly boil the liquid medicine over high heat for about 5-8 minutes, then switch to low heat and simmer, maintaining a slight boil for 40-50 minutes. Use an electronic balance to accurately weigh 1g of borneol in advance, put it in a clean porcelain mortar for later use, and sprinkle the weighed 1g of borneol into the pot 2-3 minutes before turning off the heat and stir.

[0014] S3, Filtration and Concentration

[0015] After boiling, filter the hot liquid through 3-4 layers of medical gauze into a clean glass beaker to reduce the residue, transfer the filtered decoction to a rotary evaporator, set the temperature to 40-50°C and the speed to 60-80r / min, and concentrate under reduced pressure until a thick extract is formed with a relative density of 1.2-1.3;

[0016] S4. Freeze drying

[0017] Spread the prepared thick extract on a sterile tray with a thickness of 5-8mm, put it in a freezer that has been pre-cooled to -45°C, maintain the low temperature for 2-3 hours, turn on the freezer vacuum system, maintain the vacuum degree at 10-30Pa, and slowly heat it to -20°C, keep it for 4-6 hours, then heat it to 0-0°C, and dry it for 2-3 hours.

[0018] S5. Storage

[0019] Take out the freeze-dried block from the freezer, place it in a clean agate mortar, grind it into fine powder, pass it through an 80-100 mesh sieve, accurately weigh the prepared freeze-dried powder according to the established dosage, and package it into moisture-proof and light-proof brown vials with silica gel desiccant. Seal it tightly, affix a label with the name, specification, and production date information, and store it in a cool and dry warehouse with a temperature of 2-8°C and a humidity of 45%-65%.

[0020] Compared with the prior art, the present invention has the following beneficial effects:

[0021] The present invention synthesizes the medicine by combining bezoar, borneol and calamus according to a specific weight array, and the raw materials interact with each other, so as to achieve the effect of quickly relieving the clinical symptoms of neurological deficit in the acute stage or even the ultra-early stage of cerebral infarction patients. Compared with the existing medicine or method for treating acute stage orifice blockage of cerebral infarction, the combined medicine of the present invention has significant advantages in the speed and degree of symptom relief. At the same time, natural Chinese medicine ingredients are used, and the side effects are relatively small. Patients are not prone to serious adverse reactions during the taking process, which reduces the treatment risk and is more suitable for long-term use. The drug raw materials are relatively common and low in cost, and the preparation process is simple, which can reduce the treatment cost of patients, is easy to promote and apply, can effectively reduce the economic burden of patients and their families, improve the treatment compliance of patients, and enable more patients to benefit from the treatment method. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 Schematic diagram of the changes in OGD / R and OGD / R+NBP cell treatments of the present invention;

[0023] Figure 2 This is a schematic diagram of an experiment of producing reactive oxygen species by brain microvascular endothelial cells according to the present invention;

[0024] Figure 3 Schematic diagram of the distribution and morphology of ROS and mitochondria in cells of the present invention;

[0025] Figure 4 This is a diagram showing that the orifice-opening effect of the present invention accelerates the recovery of the mental state of MCAO rats. DETAILED DESCRIPTION

[0026] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0027] Embodiment 1:

[0028] A combination drug for rapidly relieving acute stage orifice blockage in cerebral infarction: The medicinal materials are selected from high-quality bezoar, borneol and calamus, ensuring that the medicinal materials are free of mildew and insects and meet the relevant quality standards of the Chinese Pharmacopoeia. Among them, bezoar 2g, borneol 1g, calamus 10g.

[0029] A preparation method of a combined drug for rapidly relieving acute stage orifice blockage in cerebral infarction:

[0030] Pretreatment of medicinal materials

[0031] The selected bezoars and calamus were gently washed with purified water to remove surface impurities. Then, the bezoars and calamus were placed in a glass container, and sufficient purified water was added until the medicinal materials were completely immersed. The soaking time was set to 14 hours. During this period, a glass rod was used to gently stir once every 3.5 hours to ensure that the medicinal materials were fully infiltrated.

[0032] Boil

[0033] Use a ceramic casserole and pour the soaked herbs and water into the casserole. Turn on the stove and heat it with high heat. It only takes 6 minutes for the liquid medicine to boil rapidly. Then turn to low heat and maintain a slight boil for 45 minutes. At the same time, use an electronic balance to accurately weigh 1g of borneol in advance and place it in a clean porcelain mortar for later use. 2.5 minutes before turning off the heat, sprinkle the weighed 1g of borneol evenly into the pot and stir quickly with a glass rod to fully blend the borneol into the liquid medicine.

[0034] Filtration and concentration

[0035] After boiling, slowly pour the hot liquid medicine and filter it through 4 layers of medical gauze into a clean glass beaker to reduce the residue. Then, carefully transfer the filtered decoction to a rotary evaporator, set the temperature to 45°C and the speed to 70r / min, and concentrate under reduced pressure. Closely observe until a thick extract is formed with a relative density of 1.25.

[0036] Freeze drying: Carefully spread the prepared thick extract on a sterile tray with a thickness of 6mm, and then put it into a freezer that has been precooled to -45℃ and maintained at low temperature for 2.5 hours. Then turn on the freezer vacuum system, accurately maintain the vacuum degree at 20Pa, and slowly raise the temperature to -20℃ for 5 hours. Then, raise the temperature to 0℃ and dry for another 2.5 hours.

[0037] store

[0038] Take out the freeze-dried block from the freezer, place it in a clean agate mortar, slowly grind it into fine powder, and then pass it through a 90-mesh sieve. Accurately weigh the prepared freeze-dried powder according to the established dosage, and pack it into moisture-proof and light-proof brown vials with silica gel desiccant, seal it tightly, and label it with detailed information such as name, specification, production date, etc., and finally store it in a cool and dry warehouse with a temperature of 5°C and a humidity of 50%.

[0039] Embodiment 2:

[0040] A preparation method of a combined drug for rapidly relieving acute stage orifice blockage in cerebral infarction:

[0041] Purchase bezoar, borneol and calamus. The purchased bezoar has pure color and fine texture, weighing 2g; borneol has a fragrant smell and no impurities, weighing 1g; calamus has thick rhizomes and rich aroma, weighing 10g.

[0042] Equipment preparation: prepare a 2.5-liter ceramic casserole, the inner wall of which has been carefully inspected to be smooth and free of cracks; a high-precision electronic balance (accurate to 0.001g) for precise weighing; several clean and sterile glassware, including a wide-mouth bottle for soaking medicinal materials, and a beaker for collecting the filtrate; also prepare multi-layer medical gauze (3 layers), a rotary evaporator, a freeze dryer with a pre-cooling temperature of -50°C, an agate mortar, a 100-mesh sieve, and a brown medicinal bottle with a silica gel desiccant.

[0043] Pretreatment of medicinal materials

[0044] Place the bezoar and calamus in two different clean glass dishes, rinse them three times with slowly flowing purified water to remove surface dust and impurities. After washing, put both into a large glass jar, add enough purified water to immerse the herbs, and set the soaking time to 13 hours. During the soaking period, use a wooden stirring stick to gently stir once every 3 hours to ensure that all parts of the herbs are fully absorbed by water.

[0045] Boil

[0046] Carefully pour the soaked herbs and soaking water into a ceramic casserole. Turn on the gas stove and adjust to high heat. The liquid medicine will boil violently in just 7 minutes. Immediately turn to low heat and keep the liquid medicine slightly boiling for 42 minutes. At this time, use an electronic balance to accurately weigh 1g of borneol and place it in a clean porcelain mortar. 3 minutes before turning off the heat, quickly sprinkle the weighed borneol into the casserole and stir quickly with a long-handled bamboo chopstick to evenly disperse the borneol.

[0047] Filtration and concentration

[0048] After boiling, the hot liquid medicine is passed through three layers of medical gauze while hot and slowly filtered into a clean glass beaker at a moderate filtering speed to avoid splashing. After that, the filtrate is transferred to a rotary evaporator, the temperature is set to 42°C, the speed is set to 65r / min, and the vacuum concentration program is started. The operator always pays attention to the state of the liquid medicine in the evaporator until the liquid medicine is concentrated into a thick extract with a relative density of 1.22.

[0049] Freeze drying

[0050] Carefully pour the extract into a sterile tray and use a scraper to evenly spread the extract to maintain a thickness of 7mm. Place it in a freezer precooled to -45℃ and keep it at low temperature for 2 hours. Then turn on the vacuum system, accurately control the vacuum degree at 15Pa, and raise the temperature to -20℃ at a stable rate, and maintain this temperature for 4 hours. Finally, raise the temperature to 0℃ and continue drying for 2 hours.

[0051] store

[0052] Take out the freeze-dried block from the freezer, put it into an agate mortar, grind it gently into fine powder, and pass it through a 100-mesh sieve. According to the single-dose requirement, accurately weigh the freeze-dried powder and dispense it into brown vials with silica gel desiccant. The bottle is tightly sealed and labeled with the drug name, specification "0.5g / bottle", and production date. Store it in a cool and dry warehouse with a temperature of 4°C and a humidity of 55%.

[0053] This picture shows the effect of OGD / R (hypoxia-reoxygenation) treatment on nerve cells (Endothelium endothelial cells) and astrocytes (Astrocytes), and compares the staining of cells under two conditions: adding 0.5 mg / ml NBP to OGD / R treatment and only OGD / R treatment. NBP is specifically the drug prepared by the present invention.

[0054] In the figure, the left side is the OGD / R+NBP0.5mg / ml treatment group, and the right side is the OGD / R treatment group. Through the staining effects of H33342 and Rhodamine123, the changes in cell morphology and viability under different treatment conditions can be observed. H33342 staining shows the morphology of the cells, while Rhodamine123 reflects the ATP level in the cells, thereby reflecting the cell viability.

[0055] By comparing the staining effects of the two groups of cells, it can be inferred that the OGD / R+NBP treatment group may have an advantage in protecting the integrity of the BBB (blood-brain barrier) barrier function, which helps to evaluate the role of NBP in alleviating OGD / R-induced cell damage. Therefore, this picture intuitively shows the changes in cells under different treatment conditions, providing a basis for evaluating the protective effect of drugs on cells.

[0056] Figure 2 The experimental results of reactive oxygen species (ROS) produced by brain microvascular endothelial cells after inhibiting the blood-brain barrier (BBB). The image on the left shows the distribution of intracellular ROS at different time points (2 hours and 1-2 hours), and the changes in ROS generation can be observed through fluorescent photos. On the right is a histogram of ROS levels detected by flow cytometry, which quantitatively analyzes the content of intracellular ROS at different time points, and intuitively reflects the effect of inhibiting the BBB on the production of ROS by brain microvascular endothelial cells.

[0057] Figure 3 In order to promote the study of blood-brain barrier (BBB) ​​function, the metabolism and morphological reconstruction of reactive oxygen species (ROS) on mitochondria of brain microvascular endothelial cells were investigated. Through fluorescence microscopy, the images show the distribution and morphology of ROS (red fluorescence) and mitochondria (blue fluorescence) in cells, revealing the dynamic changes of ROS on mitochondria.

[0058] Figure 4 The diagram shows how the invigorating effect accelerates the recovery of the mental state of MCAO rats.

[0059] The invention mainly adopts bezoar, borneol and calamus.

[0060] Among them, bezoar is cool in nature, sweet in taste, and enters the heart and liver meridians, and has multiple functions:

[0061] Clearing heat and detoxifying: Bezoar can clear heat and detoxify, and is suitable for treating symptoms such as sore throat, mouth sores, carbuncles and furuncles caused by heat and toxic accumulation.

[0062] Resolving phlegm and initiating the orifices: Bezoar can resolve phlegm and initiating the orifices, and has a certain therapeutic effect on symptoms such as coma and delirium, stroke and phlegm syncope caused by phlegm-heat blocking the heart orifices.

[0063] Cooling the liver and calming wind: Bezoar can calm liver wind and has significant therapeutic effects on diseases such as convulsions and epilepsy in children.

[0064] Anti-inflammatory effect: Bezoar has certain anti-inflammatory effect and can reduce inflammatory response.

[0065] Choleretic effect: Bezoar has a certain stimulating effect on the gallbladder, can promote bile secretion, and is beneficial to the treatment of biliary diseases.

[0066] Calming the mind and soothing the spirit: Bezoar can slow down emotions, relieve tension and achieve a calming and soothing effect by inhibiting the central nervous system.

[0067] Regulate immunity: Bezoar contains vitamin D, sodium, calcium, magnesium, zinc and other ingredients, which can regulate the body's immune function and enhance the body's disease resistance.

[0068] Borneol is a processed product of the borneol resin of the Dipterocarpaceae plant, or a processed product synthesized by chemical methods such as camphor and turpentine. It has many functions: Clearing away heat and detoxification: Borneol can help clear the body of heat and toxins, and has a certain effect on diseases caused by exogenous heat and toxins such as colds, fever, and pharyngitis. Rejuvenating the mind: Borneol tastes spicy, cold, and has a clear fragrance. It has a certain effect of rejuvenating the mind and refreshing the mind, and is often used to treat various closed syndromes and coma. Dispelling wind and relieving pain: Borneol is often used to treat pain caused by wind and cold, such as rheumatoid arthritis and muscle pain, and can relieve pain symptoms caused by wind and cold invasion. Relieving asthma and cough: Borneol can be used to relieve the symptoms of respiratory diseases such as asthma and chronic cough, and helps to relieve asthma and cough. Antiseptic and muscle-building: When used externally, borneol can promote the healing of wounds such as skin ulcers, burns, and scalds, and has the effect of antiseptic and muscle-building. Relieving swelling and itching: For symptoms such as skin redness, swelling, and itching, borneol can reduce inflammatory reactions and relieve itching and discomfort. Promote drug absorption: Borneol can promote the transdermal absorption of other drugs and improve the efficacy of drugs.

[0069] Acorus calamus is a perennial herbaceous plant of the Araceae family. It is pungent, bitter and warm in nature. It belongs to the heart meridian and stomach meridian and has many functions: Opening the orifices and removing phlegm: Acorus calamus has a fragrant smell and has the effect of opening the orifices and removing phlegm and dampness. It is suitable for symptoms such as unclear consciousness, deafness, blurred vision and mental dullness caused by the failure of the clear yang to rise. Calming the mind and calming the spirit: Acorus calamus has an inhibitory effect on the central nervous system of the human body, so it can play a sedative and soothing role, and also relieves the symptoms of insomnia. Invigorating the spleen and stimulating the appetite: Acorus calamus contains volatile oils and has a fragrant smell. It can promote the secretion of digestive juices and inhibit abnormal fermentation, which is very beneficial to improving the health of the gastrointestinal tract. Relieving spasms and relieving pain: Acorus calamus can relieve spasms of intestinal smooth muscles, invigorate the spleen and stomach, and has a sedative effect, so it can be used for abdominal pain, and has a good effect on abdominal pain caused by acute and chronic gastritis.

[0070] In summary, the intervention of the present invention using traditional Chinese medicine is not only expected to play a positive role in the treatment of ischemic stroke, but also has good safety and tolerance. In addition, the application of traditional Chinese medicine can also achieve comprehensive promotion of primary medical and health service centers, has cost-effectiveness advantages, can reduce the economic burden of patients and their families, improve patients' treatment compliance and accessibility, and is of great significance for improving the current status of prevention and treatment of ischemic stroke in my country.

[0071] It will be appreciated that in the development of any actual implementation, as in any engineering or design project, numerous implementation-specific decisions may be made. Such a development effort may be complex and time-consuming, but will be a routine task of design, fabrication, and production for those of ordinary skill having the benefit of this disclosure without undue experimentation.

[0072] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present invention, which should all be included in the scope of the claims of the present invention.

Claims

1. A combination drug for rapidly relieving acute stage orifice blockage in cerebral infarction, characterized in that: The invention comprises the following raw materials by weight: 2g of bezoar, 1g of borneol and 10g of calamus, and the weight ratio of bezoar, borneol and calamus is 2:1:

10.

2. The method for preparing a combination drug for rapidly relieving acute stage orifice blockage in cerebral infarction according to claim 1, characterized in that: The method comprises the following preparation steps: S1. Pretreatment of medicinal materials Material selection: Select high-quality bezoar, borneol and calamus, and wash the bezoar and calamus separately. Then add purified water to the glass container containing the medicinal materials, completely immerse the bezoar and calamus medicinal materials, and extend the soaking time to 12-15 hours, stirring every 3-4 hours; S2. Boil Choose a ceramic casserole with a smooth inner wall and no cracks, with a capacity of 2-3 liters. Pour the soaked herbs and water into the casserole. First, quickly boil the liquid medicine over high heat for about 5-8 minutes, then switch to low heat and simmer, maintaining a slight boil for 40-50 minutes. Use an electronic balance to accurately weigh 1g of borneol in advance, put it in a clean porcelain mortar for later use, and sprinkle the weighed 1g of borneol into the pot 2-3 minutes before turning off the heat and stir. S3, Filtration and Concentration After boiling, filter the hot liquid through 3-4 layers of medical gauze into a clean glass beaker to reduce the residue, transfer the filtered decoction to a rotary evaporator, set the temperature to 40-50°C and the speed to 60-80r / min, and concentrate under reduced pressure until a thick extract is formed with a relative density of 1.2-1.3; S4. Freeze drying Spread the prepared thick extract on a sterile tray with a thickness of 5-8mm, put it in a freezer that has been pre-cooled to -45°C, maintain the low temperature for 2-3 hours, turn on the freezer vacuum system, maintain the vacuum degree at 10-30Pa, and slowly heat it to -20°C, keep it for 4-6 hours, then heat it to 0-0°C, and dry it for 2-3 hours. S5. Storage Take out the freeze-dried block from the freezer, place it in a clean agate mortar, grind it into fine powder, pass it through an 80-100 mesh sieve, accurately weigh the prepared freeze-dried powder according to the established dosage, and package it into moisture-proof and light-proof brown vials with silica gel desiccant. Seal it tightly, affix a label with the name, specification, and production date information, and store it in a cool and dry warehouse with a temperature of 2-8°C and a humidity of 45%-65%.

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