Active quick-acting thrombolytic drug preparation device and preparation method thereof

By designing an active fast-acting thrombolytic drug preparation device, the method of combining biological wall-breaking induction fluid with silica gel cotton layer was used to solve many problems in the existing hirudin extraction technology, and efficient and safe hirudin extraction and drug preparation were achieved, maintaining the activity of hirudin and the efficacy of the drug.

CN120000772APending Publication Date: 2025-05-16ZHICHANG PHARM (YUNNAN) CO LTD
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Patent Information

Application Number
CN202311531233.X
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2023-11-16
Publication Date
2025-05-16

AI Technical Summary

Technical Problem

The existing hirudin extraction technology uses non-drug composition inducing fluid, requires vomiting, causes harm to the living leeches, affects the survival rate of leeches, and requires high temperature drying, resulting in reduced hirudin activity and poor efficacy.

Method used

An active fast-acting thrombolysis drug preparation device was designed, using a biological wall-breaking induction liquid to combine with a silicone cotton layer, and the hirudin slurry was extracted through an extrusion mechanism to avoid high-temperature drying, maintain hirudin activity, and hirudin paste was prepared by low-temperature vacuum concentration.

Benefits of technology

It has achieved the use of non-drug inducing fluids, no need to induce vomiting, protection of leeches, maintaining hirudin activity, and improving drug efficacy, providing an efficient and safe method of hirudin extraction.

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Abstract

The invention provides an active quick-acting thrombolytic drug preparation device and a preparation method thereof. The invention provides an active quick-acting thrombolytic medicine which is prepared from the following raw material medicines in parts by weight: 3-9 parts of ligusticum wallichii extract, 6-18 parts of panax notoginseng saponins, 2-5 parts of panax notoginseng powder, 2-4 parts of active hirudin, 8-24 parts of fresh and alive earthworms and 0.5-1.5 parts of borneol, and biological induction liquid is prepared from the fresh and alive earthworms, panax notoginseng powder and purified water. The leeches are put into the cotton layer, so that the leeches suck little induction liquid and secrete a large amount of saliva, and active hirudin serous fluid can be conveniently extracted; the active quick-acting thrombolytic drug preparation device and the preparation method thereof have the advantages that non-drug composition induction liquid is not used, emetic is not needed, hurt to living leeches is avoided, the survival rate of the leeches is not affected, hirudin extraction does not need high-temperature drying, the activity of hirudin is kept, and the curative effect of the drug is guaranteed.
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Description

Technical Field

[0001] The invention relates to the technical field of active fast-acting thrombolytic preparation, and in particular to an active fast-acting thrombolytic drug preparation device and a preparation method thereof. Background Art

[0002] With the improvement of people's living standards and the change of dietary structure, the number of people suffering from thrombotic diseases has increased significantly, such as coronary heart disease, blood viscosity, headache, dizziness, cerebral thrombosis, brain tumor, etc. The above diseases have brought many inconveniences and great troubles to the lives of patients and their families, and even posed a great threat to the lives of patients. Studies have found that the above diseases are related to sodium intake, which leads to hardening of capillaries and then to the disease; and are related to fright, irritability and bad temper.

[0003] Chinese invention patent document number CN105384814B discloses a natural hirudin cyclic extraction device and extraction method, including a liquid collection box, a water pump, a tray and a feeding sleeve. The above-mentioned device cyclic extraction method includes the following steps: (1) Preparation: Select fresh animal blood, heat it to 100°C and keep it for 5 minutes for sterilization, quickly put it into the prepared cold water to cool it to room temperature, put the cooled blood clots and an appropriate amount of water into a food processor at 40,000 revolutions per minute for pulping, and adjust the viscosity to the concentration of fresh animal blood. Use this plasma as feed for leeches and a carrier for extracting hirudin. (2) Domestication and feeding: Pour the processed plasma into the liquid collecting box of the extraction device, and connect the discharge pipe and the feed pipe through the feeding sleeve, place it in the tray, operate the water pump to make the plasma circulate back and forth in the feeding sleeve (imitating the flow of animal blood in its blood vessels), and apply the processed plasma on the outer wall of the feeding sleeve to induce the domesticated hungry leeches to feed, and utilize the mechanism that they spit out saliva, i.e. hirudin, while feeding. The flowing blood takes away the saliva and extracts the hirudin; during the feeding period of the leeches, the plasma must be kept with sufficient internal pressure to fill the feeding sleeve. Collection: Collect the remaining plasma after the leeches feed, and use the vacuum freeze-dehydration method to make blood meal; adopt cobalt 60 radiation sterilization. The Chinese invention patent with document number CN201410402315.9 discloses a large-scale production method of natural hirudin, which comprises the following steps: firstly placing a living leech that has been saturated with an inducing liquid in a container, adding a certain amount of an emetic to make it spit out the saliva in the body, i.e., the crude natural hirudin liquid, wherein the emetic is a zinc sulfate solution or a mixture of zinc sulfate and ethanol; then taking out the living leech, washing it with clean water, and continuing to feed it for the next extraction; collecting the crude natural hirudin liquid in the container; adding an appropriate amount of a filler, mixing, and drying to obtain a powder product, i.e., the natural hirudin product.The Chinese invention patent with document number CN115386001A discloses a unique technology, preparation and application of a natural induction method for extracting the sucking fluid of golden-edged leeches. The invention provides the following technical solutions: A unique technology for extracting the sucking fluid of golden-edged leeches by a natural induction method, comprising the following steps: Step 1, making a special inducer: using an enema to inject a liquid inducer into a pig small intestine or an artificial casing to form a sausage shape, and wrapping a solid inducer with a 200-mesh nylon cloth; Step 2, putting the packaged inducer into a 60-mesh nylon bag, and then putting it into a wide-mouth container, fishing out the leech and putting it into the nylon bag, allowing the leech to naturally suck the inducer, and at the same time secrete a sucking fluid containing effective components such as hirudin, and when the leech is full, it will naturally stop sucking, and a sucking fluid 1 is obtained, The golden-edged leeches sucked by the natural induction method are conventionally cultured; step three, removing the solid inducer into another container, squeezing it, and washing it with a small amount of water to obtain the sucking liquid 2; step four, mixing the sucking liquid 1 and the sucking liquid 2, further precipitating, filtering, centrifuging, and drying to obtain a high-content and high-purity hirudin extract, which can be made into a variety of preparations and can be used in medicine; there are the following defects when using the above method to extract hirudin: first, the inducing liquid is not a component of the drug and needs to be fed before vomiting, which makes the hirudin impurities larger and affects the product quality; second, stimulation and squeezing to induce vomiting will cause harm to the living leech and affect the survival rate of the leech; third, the extraction of hirudin requires biochemical separation and high-temperature drying, which makes the hirudin powder lose its activity and reduces the efficacy.

[0004] Therefore, it is necessary to provide a new active fast-acting thrombolytic drug preparation device and a preparation method thereof to solve the above technical problems. Summary of the invention

[0005] The technical problem solved by the present invention is to provide an active fast-acting thrombolytic drug preparation device and a preparation method thereof, which do not use non-drug composition induction liquid, do not need vomiting, do not cause harm to the living leech, do not affect the survival rate of the leech, do not require high-temperature drying for hirudin extraction, and both maintain the activity of hirudin and ensure the efficacy of the drug.

[0006] In order to solve the above technical problems, the active fast-acting thrombolytic drug preparation device provided by the present invention comprises: a liquid receiving tank, the liquid receiving tank for storing active hirudin slurry is arranged at the bottom end of the induction tube, the interior of the induction tube is provided with a silicone cotton layer for absorbing biological wall-breaking induction liquid; the interior of the induction tube is provided with a compression mechanism for squeezing the silicone cotton layer, the compression mechanism comprises a limit plate, a pressure plate, a compression net, a first connecting rod, a second connecting rod, a piston and a connecting pipe, the interior of the induction tube is provided with the limit plate for preventing the internal pressure of the silicone cotton layer from being too large, the interior of the induction tube is slidably connected to the squeezing mechanism The pressure plate and the compression net press the silicone cotton layer; the first connecting rod is symmetrically installed at the bottom end of the induction cylinder, and the second connecting rod and the piston are slidably connected inside the first connecting rod; the two ends of the second connecting rod are respectively fixedly connected to the piston and the compression net, and the connecting pipe is installed at the bottom end of the first connecting rod; the top of the induction cylinder is a spray mechanism for spraying pure water toward the silicone cotton layer, the side wall of the induction cylinder is symmetrically installed with an extrusion mechanism for pushing the piston to move, and a driving mechanism for driving the pressure plate and the extrusion mechanism to move is arranged above the induction cylinder.

[0007] Preferably, the driving mechanism includes a compression rod, a screw rod, a bracket, a box, a motor, a first gear and a second gear. The bracket is installed on the side wall of the induction cylinder, and the box is installed on the top of the bracket. The first gear and the second gear that are meshed with each other are rotatably connected inside the box, and the motor for driving the second gear to rotate is installed on the surface of the box; the first gear is threadedly connected to the screw rod, and the screw rod connects the compression rod and the pressure plate.

[0008] Preferably, the diameter of the first gear is greater than the diameter of the second gear.

[0009] Preferably, the extrusion mechanism includes a compression plug, a spring, a storage cylinder, a first pressure rod and a second pressure rod; the storage cylinder is symmetrically installed on the side wall of the induction cylinder, the connecting tube is installed on the bottom end of the storage cylinder, the compression plug and the first pressure rod are slidably connected inside the storage cylinder, and the compression plug is fixed to the bottom end of the first pressure rod; the first pressure rod is slidably connected inside the second pressure rod, the top end of the second pressure rod abuts against the compression rod, and the two ends of the spring are respectively connected to the first pressure rod and the second pressure rod.

[0010] Preferably, the spray mechanism includes a water inlet pipe, a nozzle and a spray head; the annular nozzle is installed on the top of the induction tube, and the water inlet pipe is installed on the side wall of the nozzle; and the side wall of the nozzle is inclined at 45 degrees to install multiple spray heads.

[0011] Preferably, both ends of the induction tube are funnel-shaped structures, and the nozzle is installed at the turning point of the induction tube.

[0012] Preferably, a drain pipe is installed at the bottom end of the induction cylinder, and a valve is installed on the side wall of the drain pipe.

[0013] A method for preparing an active fast-acting thrombolytic drug, comprising the following steps:

[0014] Step 1: prepare biological wall-breaking induction liquid, the mass ratio of the materials of the biological induction liquid is: 8-24 parts of fresh earthworm, 2-5 parts of Panax notoginseng powder, and 24-72 parts of purified water; firstly, cut open the abdomen of the fresh earthworm, remove the internal organs and mud, and wash it for use; dissolve the Panax notoginseng powder with purified water, add the fresh earthworm, stir and mix thoroughly, and then use a wet ultrasonic wall-breaking pulping machine to emulsify and grind the pulp to obtain the biological wall-breaking induction liquid; the fresh earthworm has the functions of inducing living leeches to eat and stimulating leeches to secrete hirudin; the Panax notoginseng powder has the function of preventing the earthworm pulp from solidifying; and the purified water has the function of diluting;

[0015] Step 2: Collecting active hirudin slurry: Absorb the prepared biological wall-breaking induction liquid into the silica gel cotton layer, and the amount of biological induction liquid added each time is 10-20% of the silica gel cotton layer under normal conditions, so that the saturation of the collodion does not exceed 20%; Place the silica gel cotton layer on the surface of the compression net, and lay a 3 to 5 cm thick silica gel cotton layer each time, put leeches that have been hungry for 4-5 days into the silica gel cotton layer, and lay another layer of the silica gel cotton layer on the surface, so that the blood-sucking leeches can freely suck and secrete saliva. Since the leeches are in a hungry state, they can only suck very little induction liquid after contacting the collodion containing biological induction liquid, and will secrete a large amount of saliva due to the smell stimulation of the biological induction liquid. After 30-60 minutes, open the spray mechanism to pour in pure water for 15-30 seconds, so that the saturation of the collodion is 70-80%. When the watering is stopped, the driving mechanism is turned on, and the driving mechanism drives the pressing plate and the squeezing mechanism to operate, the pressing plate squeezes the silicone cotton layer downward, and at the same time, the liquid inside the squeezing mechanism enters the interior of the first connecting rod through the connecting pipe, thereby pushing the piston, the second connecting rod and the compression net to move upward, and the compression net and the pressing plate compress the silicone cotton layer up and down, and the silicone cotton layer and the leeches are squeezed together, and the liquid that flows into the collecting tank is the active hirudin slurry; during the squeezing process, the leeches are located inside the silicone cotton layer, and the limit plate prevents the internal pressure of the silicone cotton layer from being too large, thereby avoiding damage to the leeches; after repeating the above steps to extract the hirudin slurry twice, the leeches are transferred to the breeding pond for continuous feeding for 6-7 days, and saliva can be collected again;

[0016] Step 3: preparing active hirudin paste: filtering the collected active hirudin slurry with a 200-300 mesh screen and then filtering and separating and purifying it with a ceramic microfiltration membrane, and then using a low-temperature vacuum concentrator to perform low-temperature vacuum concentration to a water content of 50-60% to obtain an active hirudin paste, which is sterilized by ultrasonic sterilization at a frequency of 33kHz-40kHz for 10 minutes before use; by using low-temperature vacuum concentration technology, the feed liquid is evaporated and concentrated at a relatively low temperature, which effectively avoids traditional long-term high-temperature heating and maintains the activity of the hirudin paste; prepare 2-4 parts of active hirudin, 3-9 parts of Chuanxiong extract, 6-18 parts of Panax notoginseng total saponins, and 0.5-1.5 parts of borneol according to the following mass ratios; Chuanxiong extract and borneol are respectively ethanol (ethanol content 9 5%) is dissolved for use, and the volume ratio of ethanol to Chuanxiong extract and borneol is 1:0.5:5; the sterilized active hirudin paste is added into a mixer; Chuanxiong ethanol solution and borneol ethanol solution are added in sequence; the notoginseng total saponins prepared in step S5 are then put into the mixer; the machine is turned on and mixed to form a mixture of active and fast-acting thrombolytic drugs; the mixture is transferred into a vacuum dryer for vacuum drying, and the drying conditions adopted are: temperature 50-60°C, vacuum degree 0.08MPa; when the moisture content is less than 8%, the mixture is taken out and cooled; the dried product obtained after the mixture is dried is sterilized by a high-energy electron linear accelerator to form an active and fast-acting thrombolytic drug, which can be made into dosage forms such as dripping pills, granules, pills, capsules, tablets, powder injections, etc.

[0017] When preparing capsules or powders, the dried product is crushed and passed through a 120-mesh sieve, and sterilized using a high-energy electron linear accelerator to obtain an active fast-acting thrombolytic drug powder, and the powder is filled into capsules to obtain an active fast-acting thrombolytic drug capsule;

[0018] When making tablets or pills, the dried product is crushed and passed through a 120-mesh sieve. According to the mass ratio, 10-20 parts of starch and 1.8-3.5 parts of magnesium stearate are added to 1 part of the dried product, mixed well, pressed into tablets or pills, and sterilized using a high-energy electron linear accelerator;

[0019] When preparing the powder for injection, according to the mass percentage, 10% by weight of the active fast-acting thrombolytic drug and 0-6% of the freeze-dried additive are added to 84-90% by weight of water for injection, and stirred to dissolve; 0.1-0.3% of activated carbon is added, and the mixture is kept warm at 35-45°C for 10-15 minutes, and the carbon is removed by filtering; the injection water is supplemented to 900 parts by volume, and the mixture is stirred evenly, and tested. After the mixture is qualified, it is filtered through 0.45μm and 0.2μm microporous filter membranes respectively, and samples are taken to test the pH value, content, bacterial endotoxin and visible foreign matter until they meet the national standards, and the mixture is packaged, freeze-dried and sterilized to obtain the active fast-acting thrombolytic drug for injection.

[0020] Compared with the related art, the active fast-acting thrombolytic drug preparation device and preparation method provided by the present invention have the following beneficial effects:

[0021] The present invention provides an active fast-acting thrombolytic drug preparation device and a preparation method thereof. When extracting hirudin slurry, the prepared biological wall-breaking induction liquid is sucked into the silica gel cotton layer, and the silica gel cotton layer is placed on the surface of the compression net. After laying the silica gel cotton layer with a thickness of 3 to 5 cm, a leech that has been hungry for 4-5 days is put into the silica gel cotton layer, and another layer of the silica gel cotton layer is laid on the surface of the silica gel cotton layer, so that the blood-sucking leech can freely suck and secrete saliva. Since the leech is in a hungry state, it can only suck very little induction liquid after contacting the collodion containing biological induction liquid, and will secrete a large amount of saliva under the stimulation of the smell of the biological induction liquid. After 30-60 minutes, the spraying mechanism is turned on to spray pure water for 15-30 seconds, and the spraying is stopped when the saturation of the collodion is 70-80%, and then the driving mechanism is turned on, and the driving mechanism drives the pressing plate and the extrusion mechanism to operate, and the pressing plate squeezes the silica gel cotton layer downward, and at the same time, the liquid inside the extrusion mechanism enters the inside of the first connecting rod through the connecting pipe, thereby pushing the piston, The second connecting rod and the compression net move upward, and the compression net and the pressing plate compress the silicone cotton layer up and down, and the silicone cotton layer and the leech are squeezed together, and the liquid flowing into the collecting tank is the active hirudin slurry; during the squeezing process, the leech is located inside the silicone cotton layer, and the limit plate prevents the internal pressure of the silicone cotton layer from being too large, thereby avoiding damage to the leech, and the extracted active hirudin slurry is concentrated at low temperature to form a hirudin paste; the present invention provides a raw material weight of an active fast-acting thrombolytic drug The dosage ratio is: 3-9 parts of Chuanxiong extract, 6-18 parts of Panax notoginseng total saponins, 2-5 parts of Panax notoginseng powder, 2-4 parts of active hirudin, 8-24 parts of fresh earthworms, and 0.5-1.5 parts of borneol. Judging from the above raw material ingredients, non-drug induction liquid will not be used when preparing the hirudin paste, and living leeches are used for collection, no vomiting is required, no harm is caused to the living leeches, and the survival rate of the leeches is not affected. In addition, hirudin extraction does not require high-temperature drying, which not only maintains the activity of hirudin but also ensures the efficacy of the drug. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 A schematic diagram of the structure of the active fast-acting thrombolytic drug preparation device and preparation method provided by the present invention;

[0023] Figure 2 for Figure 1 The schematic diagram of the structure of the silicone cotton layer when it is compressed is shown;

[0024] Figure 3 for Figure 1 An enlarged schematic diagram of the structure at A shown;

[0025] Figure 4for Figure 1 An enlarged schematic diagram of the structure at B shown;

[0026] Figure 5 for Figure 2 An enlarged schematic diagram of the structure at position C is shown;

[0027] Figure 6 for Figure 1 Schematic diagram of the internal structure of the driving mechanism shown.

[0028] Numbers in the figure: 1. liquid receiving tank, 2. induction cylinder, 21. drain pipe, 22. valve, 3. silicone cotton layer, 4. compression mechanism, 41. limit plate, 42. pressure plate, 43. compression net, 44. first connecting rod, 45. second connecting rod, 46. piston, 47. connecting pipe, 5. extrusion mechanism, 51. compression plug, 52. spring, 53. storage cylinder, 54. first pressure rod, 55. second pressure rod, 6. spray mechanism, 61. water inlet pipe, 62. spray pipe, 63. spray head, 7. driving mechanism, 71. compression rod, 72. screw, 73. bracket, 74. box, 75. motor, 76. first gear, 77. second gear. DETAILED DESCRIPTION

[0029] The present invention will be further described below in conjunction with the accompanying drawings and implementation modes.

[0030] See also Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 and Figure 6, wherein the active fast-acting thrombolytic drug preparation device comprises: a liquid receiving tank 1, the liquid receiving tank 1 for storing active hirudin slurry is arranged at the bottom end of the induction tube 2, and the induction tube 2 is provided with a silicone cotton layer 3 for absorbing biological wall-breaking induction liquid; the induction tube 2 is provided with a compression mechanism 4 for squeezing the silicone cotton layer 3, the compression mechanism 4 comprises a limit plate 41, a pressure plate 42, a compression net 43, a first connecting rod 44, a second connecting rod 45, a piston 46 and a connecting pipe 47, the limit plate 41 for preventing the internal pressure of the silicone cotton layer 3 from being too large is installed inside the induction tube 2, and the inside of the induction tube 2 is slidably connected to the silicone cotton layer 3 for squeezing the silicone cotton layer 3. The pressure plate 42 and the compression net 43; the first connecting rod 44 is symmetrically installed at the bottom end of the induction cylinder 2, and the inside of the first connecting rod 44 is slidably connected to the second connecting rod 45 and the piston 46; the two ends of the second connecting rod 45 are respectively fixedly connected to the piston 46 and the compression net 43, and the bottom end of the first connecting rod 44 is installed with the connecting pipe 47; the top of the induction cylinder 2 sprays a spray mechanism 6 for spraying pure water toward the silicone cotton layer 3, and the side wall of the induction cylinder 2 is symmetrically installed with an extrusion mechanism 5 for pushing the piston 46 to move, and a driving mechanism 7 for driving the pressure plate 42 and the extrusion mechanism 5 to move is arranged above the induction cylinder 2.

[0031] The driving mechanism 7 includes a compression rod 71, a screw rod 72, a bracket 73, a box body 74, a motor 75, a first gear 76 and a second gear 77. The bracket 73 is installed on the side wall of the induction tube 2, and the box body 74 is installed on the top of the bracket 73. The first gear 76 and the second gear 77 that are meshed with each other are rotatably connected inside the box body 74. The motor 75 for driving the second gear 77 to rotate is installed on the surface of the box body 74; the first gear 76 is threadedly connected to the screw rod 72, and the screw rod 72 connects the compression rod 71 and the pressing plate 42. When the screw rod 72 needs to rotate, the motor 75 is powered on and operated, and the motor 75 drives the second gear 77 to rotate, and the second gear 77 drives the first gear 76 to rotate. The diameter of the first gear 76 is larger than the diameter of the second gear 77, so that the second gear 77 drives the first gear 76 to rotate more labor-saving, and the first gear 76 is threadedly connected to the screw rod 72. Using the principle of spiral transmission, the first gear 76 drives the screw rod 72 to move up and down.

[0032] The squeezing mechanism 5 includes a compression plug 51, a spring 52, a storage cylinder 53, a first pressure rod 54 and a second pressure rod 55. The storage cylinder 53 is symmetrically installed on the side wall of the induction cylinder 2, and the connecting pipe 47 is installed at the bottom end of the storage cylinder 53. The compression plug 51 and the first pressure rod 54 are slidably connected inside the storage cylinder 53, and the compression plug 51 is fixed to the bottom end of the first pressure rod 54; the first pressure rod 54 is slidably connected inside the second pressure rod 55, and the top end of the second pressure rod 55 abuts against the compression rod 71, and the two ends of the spring 52 are respectively connected to the first pressure rod 54 and the second pressure rod 55. When the screw rod 72 moves up and down, it drives the compression rod 71 to move, and the compression rod 71 moves downward to squeeze the second pressure rod 55 downward. The second pressure rod 55 moves downward to compress the spring 52 and the first pressure rod 54. The first pressure rod 54 is compressed and pushes the compression plug 51 to move inside the storage cylinder 53, so that the liquid inside the storage cylinder 53 enters the first connecting rod 44 through the connecting tube 47 and pushes the piston 46 to move upward; when the second pressure rod 55 moves downward, the movement of the second pressure rod 55 inside the first pressure rod 54 compresses the spring 52 at the same time, and the spring 52 symmetrically buffers the movement of the second pressure rod 55. When the compression net 43 contacts the limit block 41, the liquid inside the storage cylinder 53 cannot enter the first connecting rod 44, and the second pressure rod 55 continues to move downward inside the first pressure rod 54.

[0033] The spray mechanism 6 includes a water inlet pipe 61, a nozzle 62 and a nozzle 63. The top of the induction tube 2 is provided with a ring-shaped nozzle 62, and the side wall of the nozzle 62 is provided with the water inlet pipe 61. The side wall of the nozzle 62 is inclined at 45 degrees to install a plurality of nozzles 63. When spraying water, the water inlet pipe 61 is connected to the water source, and pure water enters the interior of the nozzle 63 through the water inlet pipe 61 and the nozzle 62. The water is sprayed downward through the nozzle 63, so that the water wets the silicone cotton layer 3.

[0034] Both ends of the induction tube 2 are funnel-shaped structures, and the nozzle 62 is installed at the turning point of the induction tube 2 to prevent the pressure plate 42 from contacting the nozzle 62 when moving up and down.

[0035] A drain pipe 21 is installed at the bottom end of the induction cylinder 2 , and a valve 22 is installed on the side wall of the drain pipe 21 . When the valve 22 is opened, the liquid in the induction cylinder 2 flows into the liquid receiving tank 1 through the drain pipe 21 .

[0036] A method for preparing an active fast-acting thrombolytic drug, comprising the following steps:

[0037] Step 1: prepare biological wall-breaking induction liquid, the mass ratio of the materials of the biological induction liquid is: 8-24 parts of fresh earthworm, 2-5 parts of Panax notoginseng powder, and 24-72 parts of purified water; firstly, cut open the abdomen of the fresh earthworm, remove the internal organs and mud, and wash it for use; dissolve the Panax notoginseng powder with purified water, add the fresh earthworm, stir and mix thoroughly, and then use a wet ultrasonic wall-breaking pulping machine to emulsify and grind the pulp to obtain the biological wall-breaking induction liquid; the fresh earthworm has the functions of inducing living leeches to eat and stimulating leeches to secrete hirudin; the Panax notoginseng powder has the function of preventing the earthworm pulp from solidifying; and the purified water has the function of diluting;

[0038] Step 2: Collecting active hirudin slurry: Absorb the prepared biological wall-breaking induction liquid into the silica gel cotton layer 3, and the amount of biological induction liquid added each time is 10-20% of the silica gel cotton layer 3 under normal conditions, so that the saturation of the silica gel cotton does not exceed 20%; Place the silica gel cotton layer 3 on the surface of the compression net 43, and lay a 3 to 5 cm thick silica gel cotton layer 3 each time, put the leeches that have been hungry for 4-5 days into the silica gel cotton layer 3, and lay another layer of the silica gel cotton layer 3 on the surface of the silica gel cotton layer 3, so that the blood-sucking leeches can suck freely and secrete saliva. Since the leeches are in a hungry state, After touching the collodion containing biological induction liquid, only a very small amount of induction liquid can be sucked. The odor of the biological induction liquid will stimulate the secretion of a large amount of saliva. After 30-60 minutes, the spray mechanism 6 is turned on to spray pure water for 15-30 seconds. When the saturation of the collodion reaches 70-80%, the spraying is stopped. Then the motor 75 drives the second gear 77 to rotate, and the second gear 77 drives the first gear 76 to rotate. The first gear 76 is threadedly connected to the screw rod 72. The screw rod 72 and the pressing plate 4 are driven by the principle of screw transmission. 2 moves downward, the pressing plate 42 presses the silicone cotton layer 3 downward, the screw rod 72 moves downward to drive the compression rod 71 to move, the compression rod 71 moves downward to press the second compression rod 55 downward, the second compression rod 55 moves downward to compress the spring 52 and the first compression rod 54, the first compression rod 54 is compressed to push the compression plug 51 to move inside the storage cylinder 53, so that the liquid inside the storage cylinder 53 enters the inside of the first connecting rod 44 through the connecting pipe 47, thereby pushing the piston 4 6. The second connecting rod 45 and the compression net 43 move upward, and the compression net 43 and the pressing plate 42 compress the silicone cotton layer 3 up and down, and the silicone cotton layer 3 and the leech are squeezed together, and the liquid flowing into the collecting tank 1 is the active hirudin slurry; during the squeezing process, the leech is located inside the silicone cotton layer 3, and the limiting plate 41 prevents the internal pressure of the silicone cotton layer 3 from being too high, thereby avoiding damage to the leech; after repeating the above steps to extract the hirudin slurry twice, the leech is transferred to the breeding pond to continue feeding for 6-7 days, and saliva can be collected again;

[0039] Step 3: preparing active hirudin paste: filtering the collected active hirudin slurry with a 200-300 mesh screen and then filtering and separating and purifying it with a ceramic microfiltration membrane, and then using a low-temperature vacuum concentrator to perform low-temperature vacuum concentration to a water content of 50-60% to obtain an active hirudin paste, which is sterilized by ultrasonic sterilization at a frequency of 33kHz-40kHz for 10 minutes before use; by using low-temperature vacuum concentration technology, the feed liquid is evaporated and concentrated at a relatively low temperature, which effectively avoids traditional long-term high-temperature heating and maintains the activity of the hirudin paste; prepare 2-4 parts of active hirudin, 3-9 parts of Chuanxiong extract, 6-18 parts of Panax notoginseng total saponins, and 0.5-1.5 parts of borneol according to the following mass ratios; Chuanxiong extract and borneol are respectively ethanol (ethanol content 9 5%) is dissolved for use, and the volume ratio of ethanol to Chuanxiong extract and borneol is 1:0.5:5; the sterilized active hirudin paste is added into a mixer; Chuanxiong ethanol solution and borneol ethanol solution are added in sequence; the notoginseng total saponins prepared in step S5 are then put into the mixer; the machine is turned on and mixed to form a mixture of active and fast-acting thrombolytic drugs; the mixture is transferred into a vacuum dryer for vacuum drying, and the drying conditions adopted are: temperature 50-60°C, vacuum degree 0.08MPa; when the moisture content is less than 8%, the mixture is taken out and cooled; the dried product obtained after the mixture is dried is sterilized by a high-energy electron linear accelerator to form an active and fast-acting thrombolytic drug, which can be made into dosage forms such as dripping pills, granules, pills, capsules, tablets, powder injections, etc.

[0040] When preparing capsules or powders, the dried product is crushed and passed through a 120-mesh sieve, and sterilized using a high-energy electron linear accelerator to obtain an active fast-acting thrombolytic drug powder, and the powder is filled into capsules to obtain an active fast-acting thrombolytic drug capsule;

[0041] When making tablets or pills, the dried product is crushed and passed through a 120-mesh sieve. According to the mass ratio, 10-20 parts of starch and 1.8-3.5 parts of magnesium stearate are added to 1 part of the dried product, mixed well, pressed into tablets or pills, and sterilized using a high-energy electron linear accelerator;

[0042] When preparing the powder for injection, according to the mass percentage, 10% by weight of the active fast-acting thrombolytic drug and 0-6% of the freeze-dried additive are added to 84-90% by weight of water for injection, and stirred to dissolve; 0.1-0.3% of activated carbon is added, and the mixture is kept warm at 35-45°C for 10-15 minutes, and the carbon is removed by filtering; the injection water is supplemented to 900 parts by volume, and the mixture is stirred evenly, and tested. After the mixture is qualified, it is filtered through 0.45μm and 0.2μm microporous filter membranes respectively, and samples are taken to test the pH value, content, bacterial endotoxin and visible foreign matter until they meet the national standards, and the mixture is packaged, freeze-dried and sterilized to obtain the active fast-acting thrombolytic drug for injection.

[0043] The above descriptions are merely embodiments of the present invention and are not intended to limit the patent scope of the present invention. Any equivalent structure or equivalent process transformation made using the contents of the present invention specification and drawings, or directly or indirectly applied in other related technical fields, are also included in the patent protection scope of the present invention.

Claims

1. An active fast-acting thrombolytic drug preparation device, characterized in that: include: A liquid receiving tank (1) for storing active hirudin slurry is arranged at the bottom end of an induction tube (2); a silicone cotton layer (3) for absorbing biological wall-breaking induction liquid is arranged inside the induction tube (2); a compression mechanism (4) for squeezing the silicone cotton layer (3) is arranged inside the induction tube (2); the compression mechanism (4) comprises a limit plate (41), a pressure plate (42), a compression net (43), a first connecting rod (44), a second connecting rod (45), a piston (46) and a connecting pipe (47); a silicone cotton layer (3) is arranged inside the induction tube (2) for preventing the silicone cotton layer from The limiting plate (41) is used to prevent excessive internal pressure of the layer (3); the internal sliding connection of the induction cylinder (2) is used to extrude the pressure plate (42) and the compression net (43) of the silicone cotton layer (3); the first connecting rod (44) is symmetrically installed at the bottom end of the induction cylinder (2); the internal sliding connection of the first connecting rod (44) is used to connect the second connecting rod (45) and the piston (46); the two ends of the second connecting rod (45) are respectively fixedly connected to the piston (46) and the compression net (43); the bottom end of the first connecting rod (44) is installed with the connecting pipe (47); The top of the induction cylinder (2) is provided with a spray mechanism (6) for spraying pure water toward the silicone cotton layer (3), the side wall of the induction cylinder (2) is symmetrically provided with an extrusion mechanism (5) for pushing the piston (46) to move, and a driving mechanism (7) for driving the pressing plate (42) and the extrusion mechanism (5) to move is provided above the induction cylinder (2).

2. The active fast-acting thrombolytic drug preparation device according to claim 1, characterized in that: The driving mechanism (7) comprises a compression rod (71), a screw rod (72), a bracket (73), a box (74), a motor (75), a first gear (76) and a second gear (77); the bracket (73) is installed on the side wall of the induction tube (2); the box (74) is installed on the top of the bracket (73); the first gear (76) and the second gear (77) which are meshed with each other are rotatably connected inside the box (74); the motor (75) for driving the second gear (77) to rotate is installed on the surface of the box (74); the first gear (76) and the screw rod (72) are threadedly connected, and the screw rod (72) is connected to the compression rod (71) and the pressure plate (42).

3. The active fast-acting thrombolytic drug preparation device according to claim 2, characterized in that: The diameter of the first gear (76) is greater than the diameter of the second gear (77).

4. The active fast-acting thrombolytic drug preparation device according to claim 2, characterized in that: The squeezing mechanism (5) comprises a compression plug (51), a spring (52), a storage cylinder (53), a first pressure rod (54) and a second pressure rod (55); the storage cylinder (53) is symmetrically mounted on the side wall of the induction cylinder (2); the connecting tube (47) is mounted on the bottom end of the storage cylinder (53); the compression plug (51) and the first pressure rod (54) are slidably connected inside the storage cylinder (53), and the compression plug (51) is fixed to the bottom end of the first pressure rod (54); the first pressure rod (54) is slidably connected inside the second pressure rod (55), the top end of the second pressure rod (55) abuts against the compression rod (71), and the two ends of the spring (52) are respectively connected to the first pressure rod (54) and the second pressure rod (55).

5. The active fast-acting thrombolytic drug preparation device according to claim 1, characterized in that: The spray mechanism (6) comprises a water inlet pipe (61), a spray pipe (62) and a spray head (63); the top end of the induction tube (2) is provided with the annular spray pipe (62); the side wall of the spray pipe (62) is provided with the water inlet pipe (61); and the side wall of the spray pipe (62) is provided with a plurality of spray heads (63) at an angle of 45 degrees.

6. The active fast-acting thrombolytic drug preparation device according to claim 5, characterized in that: Both ends of the induction tube (2) are funnel-shaped structures, and the nozzle (62) is installed at the turning point of the induction tube (2).

7. The active fast-acting thrombolytic drug preparation device according to claim 1, characterized in that: A drainage pipe (21) is installed at the bottom end of the induction cylinder (2), and a valve (22) is installed on the side wall of the drainage pipe (21).

8. The active fast-acting thrombolytic drug preparation device according to any one of claims 1 to 7, characterized in that: A method for preparing an active fast-acting thrombolytic drug comprises the following steps: Step 1: prepare biological wall-breaking induction liquid, the mass ratio of the materials of the biological induction liquid is: 8-24 parts of fresh earthworm, 2-5 parts of Panax notoginseng powder, and 24-72 parts of purified water; firstly, cut open the abdomen of the fresh earthworm, remove the internal organs and mud, and wash it for use; dissolve the Panax notoginseng powder with purified water, add the fresh earthworm, stir and mix thoroughly, and then use a wet ultrasonic wall-breaking pulping machine to emulsify and grind the pulp to obtain the biological wall-breaking induction liquid; the fresh earthworm has the functions of inducing living leeches to eat and stimulating leeches to secrete hirudin; the Panax notoginseng powder has the function of preventing the earthworm pulp from solidifying; and the purified water has the function of diluting; Step 2: Collecting active hirudin slurry: Absorb the prepared biological wall-breaking induction liquid into the silica gel cotton layer (3), and the amount of biological induction liquid added each time is 10-20% of the silica gel cotton layer (3) under normal conditions, so that the saturation of the collodion does not exceed 20%; Place the silica gel cotton layer (3) on the surface of the compression net (43), and lay a 3 to 5 cm thick silica gel cotton layer (3) each time, put leeches that have been hungry for 4-5 days into the silica gel cotton layer (3), and lay another layer of the silica gel cotton layer (3) on the surface, so that the blood-sucking leeches can freely suck and secrete saliva. Since the leeches are in a hungry state, they can only suck very little induction liquid after contacting the collodion containing biological induction liquid, and will secrete a large amount of saliva under the stimulation of the smell of the biological induction liquid. After 30-60 minutes, open the spray mechanism (6) to pour pure water, and pour it for 15-30 seconds. When the saturation of the collodion reaches 70-80%, stop pouring water, and then open the driving mechanism (7). The driving mechanism (7) drives the pressing plate (42) and the squeezing mechanism (5) to operate, the pressing plate (42) squeezes the silicone cotton layer (3) downwards, and at the same time, the liquid inside the squeezing mechanism (5) enters the inside of the first connecting rod (44) through the connecting pipe (47), thereby pushing the piston (46), the second connecting rod (45) and the compression net (43) to move upwards, the compression net (43) and the pressing plate (42) compress the silicone cotton layer (3) up and down, the silicone cotton layer (3) and the leech are squeezed together, and the liquid flowing into the collecting tank (1) is the active hirudin slurry; during the squeezing process, the leech is located inside the silicone cotton layer (3), and the limiting plate (41) prevents the internal pressure of the silicone cotton layer (3) from being too high, thereby avoiding damage to the leech; after repeating the above steps to extract the hirudin slurry twice, the leech is transferred to the breeding pond for continuous feeding for 6-7 days, and saliva can be collected again; Step 3: preparing active hirudin paste: filtering the collected active hirudin slurry with a 200-300 mesh screen and then filtering and separating and purifying it with a ceramic microfiltration membrane, and then using a low-temperature vacuum concentrator to perform low-temperature vacuum concentration to a water content of 50-60% to obtain an active hirudin paste, which is sterilized by ultrasonic sterilization at a frequency of 33kHz-40kHz for 10 minutes before use; by using low-temperature vacuum concentration technology, the feed liquid is evaporated and concentrated at a relatively low temperature, which effectively avoids traditional long-term high-temperature heating and maintains the activity of the hirudin paste; prepare 2-4 parts of active hirudin, 3-9 parts of Chuanxiong extract, 6-18 parts of Panax notoginseng total saponins, and 0.5-1.5 parts of borneol according to the following mass ratios; Chuanxiong extract and borneol are respectively ethanol (ethanol content 9 5%) is dissolved for use, and the volume ratio of ethanol to Chuanxiong extract and borneol is 1:0.5:5; the sterilized active hirudin paste is added into a mixer; Chuanxiong ethanol solution and borneol ethanol solution are added in sequence; the notoginseng total saponins prepared in step S5 are then put into the mixer; the machine is turned on and mixed to form a mixture of active and fast-acting thrombolytic drugs; the mixture is transferred into a vacuum dryer for vacuum drying, and the drying conditions adopted are: temperature 50-60°C, vacuum degree 0.08MPa; when the moisture content is less than 8%, the mixture is taken out and cooled; the dried product obtained after the mixture is dried is sterilized by a high-energy electron linear accelerator to form an active and fast-acting thrombolytic drug, which can be made into dosage forms such as dripping pills, granules, pills, capsules, tablets, powder injections, etc. When preparing capsules or powders, the dried product is crushed and passed through a 120-mesh sieve, and sterilized using a high-energy electron linear accelerator to obtain an active fast-acting thrombolytic drug powder, and the powder is filled into capsules to obtain an active fast-acting thrombolytic drug capsule; When making tablets or pills, the dried product is crushed and passed through a 120-mesh sieve. According to the mass ratio, 10-20 parts of starch and 1.8-3.5 parts of magnesium stearate are added to 1 part of the dried product, mixed well, pressed into tablets or pills, and sterilized using a high-energy electron linear accelerator; When preparing the powder for injection, according to the mass percentage, 10% by weight of the active fast-acting thrombolytic drug and 0-6% of the freeze-dried additive are added to 84-90% by weight of water for injection, and stirred to dissolve; 0.1-0.3% of activated carbon is added, and the mixture is kept warm at 35-45°C for 10-15 minutes, and the carbon is removed by filtering; the injection water is supplemented to 900 parts by volume, and the mixture is stirred evenly, and tested. After the mixture is qualified, it is filtered through 0.45μm and 0.2μm microporous filter membranes respectively, and samples are taken to test the pH value, content, bacterial endotoxin and visible foreign matter until they meet the national standards, and the mixture is packaged, freeze-dried and sterilized to obtain the active fast-acting thrombolytic drug for injection.

Citation Information

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