Microbubble particles for gastrointestinal tract ultrasonic detection and production process

Abstract

The invention discloses gastrointestinal tract microbubble particles and a production process, the microbubble particles comprise activated carbon particles, pores of the activated carbon particles are filled with gas, the gas material is sulfur hexafluoride, perfluoropropane or perfluorobutane, and a shell is arranged on the outer side of the activated carbon particles; the process comprises the following steps in sequence: a, putting activated carbon particles into a carbonization furnace, and vacuumizing the carbonization furnace to discharge air in the activated carbon particles; b, injecting gas into the carbonization furnace until the air pressure in the carbonization furnace reaches the standard atmospheric pressure, and filling the pores of the activated carbon particles with the gas under the standard atmospheric pressure; c, the carbonization furnace is heated to 650-700 DEG C, an atomized closed-cell solution is sprayed into the carbonization furnace, after the closed-cell solution is sprayed, heat preservation is conducted for 5 min or above, and the activated carbon particles are taken out after the carbonization furnace is cooled; and d, coating the outer sides of the active carbon particles with a shell. The invention has the advantage that the internal gas is not easy to lose.

Description

Technical Field

[0001] The invention belongs to the field of gastrointestinal microbubble contrast agents, and in particular relates to gastrointestinal microbubble particles and a production process. Background Art

[0002] Before gastrointestinal ultrasound examination, the examinee is often asked to take microbubble contrast agent. The core component of microbubble contrast agent is microbubble particles. The structure of microbubble particles includes a gas core. Common materials for the gas core include sulfur hexafluoride (SF6), perfluoropropane (C3F8), perfluorobutane (C4F 10 ), a shell is arranged outside the gas core, and the shell is made of biocompatible materials, such as phospholipids and albumin, and the shell wraps the gas core to form microbubble particles. When the microbubble particles encounter ultrasound, the gas-liquid interface vibrates violently, and the reflected energy is more than 100 times higher than that of the surrounding soft tissue, making the gastrointestinal cavity present a bright signal, which forms a sharp contrast with the low-echo mucosal layer and muscle layer, thus making the angiography results clear.

[0003] Since the contrast agent needs a certain amount of time to diffuse after entering the gastrointestinal tract, it needs to be taken in advance before the B-ultrasound examination, and then wait in line for the number to be called after taking it. However, this waiting time is not stable. There may be a large number of people being examined in front or there may be difficulties in the examination, which requires more time and increases the waiting time. During this period, the microbubble particles have been corroded by gastric acid and decomposed by pepsin when passing through the stomach. After entering the gastrointestinal tract, they are decomposed by digestive enzymes and alkaline environment in the intestine. The shell is easily damaged, resulting in gas loss, which is not conducive to ultrasound examination. Therefore, there is an urgent need for microbubble particles whose internal gas is not easily lost. Summary of the invention

[0004] The purpose of the present invention is to provide a microbubble particle for gastrointestinal ultrasound detection and a production process. The present invention has the advantage that the internal gas is not easy to be lost.

[0005] The technical solution of the present invention is: a kind of microbubble particles for gastrointestinal ultrasound detection, including activated carbon particles, the pores of the activated carbon particles are filled with gas, the gas material is sulfur hexafluoride, perfluoropropane or perfluorobutane, and a shell is provided on the outside of the activated carbon particles.

[0006] In the aforementioned microbubble particles for gastrointestinal ultrasound detection, the gas material is perfluorobutane.

[0007] In the aforementioned microbubble particles for gastrointestinal ultrasound detection, the fineness of the activated carbon particles is 150-220 meshes.

[0008] The production process of the aforementioned microbubble particles comprises the following steps in sequence:

[0009] a. Put the activated carbon particles into the carbonization furnace, and evacuate the carbonization furnace to discharge the air in the activated carbon particles;

[0010] b. Inject gas into the carbonization furnace until the air pressure inside the carbonization furnace reaches standard atmospheric pressure, and fill the pores of the activated carbon particles with gas under standard atmospheric pressure;

[0011] c. Heat the carbonization furnace to 650 - 700 °C, and spray atomized closed-cell solution into the carbonization furnace. The closed-cell solution includes glycerol, alcohol, and sucrose. After spraying the closed-cell solution, keep it warm for more than 5 minutes, and then take out the activated carbon particles after the carbonization furnace cools down;

[0012] d. Coat the outer side of the activated carbon particles with a shell.

[0013] In the production process of the aforementioned microbubble particles, in step a, when evacuating, the carbonization furnace rotates; in step b, when injecting gas into the carbonization furnace, the carbonization furnace rotates; in step c, when spraying atomized closed-cell solution into the carbonization furnace, the carbonization furnace rotates.

[0014] In the production process of the aforementioned microbubble particles, in step c, the weight of the sprayed closed-cell solution is 5% - 10% of the weight of the activated carbon particles in the carbonization furnace.

[0015] In the production process of the aforementioned microbubble particles, the ratio of glycerol, alcohol, and sucrose in the closed-cell solution is 1:2:1.

[0016] In the production process of the aforementioned microbubble particles, the structure of the carbonization furnace includes a barrel horizontally arranged axially. The bottom of the barrel is provided with a support structure, the barrel is provided with a driving mechanism, the barrel is provided with a heating mechanism, a pipeline is arranged axially on the barrel, the pipeline is rotatably connected to the barrel, vacuum valves and liquid spraying valves are respectively arranged at both ends of the pipeline, both the vacuum valves and the liquid spraying valves are located outside the barrel, a plurality of atomizing nozzles are arranged at the bottom of the pipeline, an inlet and outlet is arranged at one end of the barrel, the inlet and outlet is close to the inner side wall of the barrel, a screw is arranged inside the barrel, the screw is close to the inner wall of the barrel, one end of the screw is close to the inlet and outlet, and the other end of the screw extends out of the barrel and is connected to a first motor.

[0017] In the production process of the aforementioned microbubble particles, a counterweight is arranged outside the barrel, the counterweight is connected to the pipeline through a connecting rod, and the connecting rod is detachably connected to the pipeline.

[0018] In the production process of the aforementioned microbubble particles, there are two support structures. The two support structures are respectively close to both ends of the barrel. The support structure includes support wheels respectively located on both sides of the bottom of the barrel. The support wheels are connected to the ground through a first bracket, and the support wheels are rotatably connected to the first bracket;

[0019] The driving mechanism includes a second motor located below the barrel. The second motor is connected to the ground through a second bracket. A gear is arranged at the output end of the second motor, and a gear ring is meshed above the gear. The gear ring is fixed to the barrel;

[0020] The heating mechanism includes a sleeve located outside the barrel. An incineration chamber is formed between the sleeve and the barrel. A plurality of flame nozzles are provided in the incineration chamber. Baffles connecting the barrel are provided at both ends of the sleeve. An air inlet hole is provided on one of the baffles, and a smoke exhaust port is provided on the other baffle. The baffle is rotatably connected to the barrel, and the barrel is connected to the ground through a third support.

[0021] Compared with the prior art, the housing of the present invention has activated carbon particles that are harmless to the human body. The abundant pores inside the activated carbon particles are used to accommodate gas. The activated carbon particles play a role as a skeleton to adsorb gas. After the outer housing is damaged, the gas is not easily lost. The majority of the pores of the activated carbon are sealed with a closed-pore solution, further preventing gas loss. Therefore, the present invention has the advantage that the internal gas is not easily lost. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 It is a micrograph of the activated carbon particles obtained in step c of Example 2.

[0023] Figure 2 It is a micrograph of the activated carbon particles in step a of Example 2.

[0024] Figure 3 It is a schematic structural diagram of the carbonization furnace of Example 3.

[0025] Figure 4 It is a schematic cross-sectional view of the barrel of the carbonization furnace of Example 3.

[0026] Figure 5 It is a picture of the B-ultrasound examination after using the perfluorobutane gas material microbubble particles of Example 1 for 120 minutes.

[0027] Figure 6 It is a picture of the B-ultrasound examination after using the existing perfluorobutane gas material microbubble particles for 120 minutes.

[0028] The reference signs in the drawings are: 1 - barrel, 2 - pipeline, 3 - vacuum valve, 4 - liquid spraying valve, 5 - atomizing nozzle, 6 - feeding and discharging port, 7 - screw, 8 - first motor, 9 - counterweight, 10 - connecting rod, 11 - supporting wheel, 12 - first support, 13 - second motor, 14 - second support, 15 - gear, 16 - gear ring, 17 - sleeve, 18 - incineration chamber, 19 - flame nozzle, 20 - baffle, 21 - air inlet hole, 22 - smoke exhaust port, 23 - third support, 24 - stirring plate. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0029] The present invention will be further described below in conjunction with the drawings and embodiments, but it shall not be used as a basis for limiting the present invention.

[0030] Example 1: A microbubble particle for gastrointestinal ultrasound detection, comprising activated carbon particles. The pores of the activated carbon particles are filled with a gas, and the gas material is sulfur hexafluoride, perfluoropropane or perfluorobutane. A shell is provided outside the activated carbon particles, and the shell material is a biocompatible material, such as phospholipid or albumin. The fineness of the activated carbon particles is 150 - 220 mesh. This fineness setting takes into account gastrointestinal tolerance. Too coarse particles may cause mechanical irritation to the gastrointestinal mucosa, triggering adverse reactions such as pain and inflammation, while too fine particles have a reduced residence time in the gastrointestinal tract, making it easy for the user to miss the ultrasound examination time range.

[0031] Example 2: The production process of the microbubble particles of Example 1, including the following sequential steps:

[0032] a. Put 50 kg of activated carbon particles into a carbonization furnace. The carbonization furnace is evacuated. When evacuating, the carbonization furnace rotates to make the activated carbon particles tumble, so that the air in the activated carbon particles can be smoothly discharged. The activated carbon particles use Fujian Yuanli pharmaceutical powdered activated carbon.

[0033] b. Inject a gas into the carbonization furnace. The carbonization furnace keeps rotating when injecting the gas until the air pressure in the carbonization furnace reaches the standard atmospheric pressure. Under the standard atmospheric pressure, the pores of the activated carbon particles are filled with the gas at normal pressure. Since the activated carbon particles have less internal air content after evacuation, the filling amount of sulfur hexafluoride, perfluoropropane or perfluorobutane is large, which helps to improve the ultrasound contrast effect.

[0034] c. Heat the carbonization furnace to 650 - 700 °C, and spray 4 kg of atomized closed-cell solution into the carbonization furnace. The carbonization furnace keeps rotating when spraying the closed-cell solution to make the closed-cell solution evenly contact the activated carbon particles. The closed-cell solution includes glycerol, alcohol and sucrose, and the ratio of glycerol, alcohol and sucrose is 1:2:1. After spraying the closed-cell solution, keep it warm for more than 5 min, stop heating the carbonization furnace, and take out the activated carbon particles after the furnace cools down.

[0035] d. Coat a shell outside the activated carbon particles. The method of coating a shell outside the activated carbon particles is the same as the prior art. For example, using the spray drying method, mix the activated carbon particles with a phospholipid solution or an albumin solution into a slurry, form tiny droplets through a spraying device, and the droplets are quickly dried in a hot air stream, so that the coating material forms a solid shell on the surface of the activated carbon particles.

[0036] The carbonization furnace can adopt a BDTHJ1200 type vacuum carbonization furnace or a THL1183 type horizontal rotary carbonization furnace.

[0037] The characteristics of the microbubble particles obtained by the above method are:

[0038] First, the shell contains activated carbon particles that are harmless to the human body. The abundant pores inside the activated carbon particles are used to hold the gas. The activated carbon particles act as a skeleton to adsorb the gas. After the external shell is damaged, the gas is not easily lost.

[0039] For the use of sulfur hexafluoride, perfluoropropane, and perfluorobutane, perfluorobutane is the best. The adsorption capacity of activated carbon for high-boiling point perfluorocarbon gas is higher than that for low-boiling point perfluorocarbon gas. This is mainly because high-boiling point gas has stronger intermolecular forces, which makes it easier to be adsorbed on the surface of activated carbon. Perfluorobutane has the highest boiling point, which makes the activated carbon adsorb the most perfluorobutane, reflecting that the activated carbon has the greatest adsorption capacity for perfluorobutane, so when perfluorobutane is used, the gas is least likely to be lost.

[0040] Second, after the gas is injected into the activated carbon particles, most of the pores of the activated carbon are closed with a closed-pore solution to further prevent gas loss. The closed-pore solution is carbonized at high temperature, and the carbonized carbon molecules grow at the pore openings of the activated carbon, blocking the pores. The closed-pore solution is prepared in proportion using glycerol, alcohol, and sucrose, mainly considering that the pore opening diameters of activated carbon vary greatly, including micropores <2nm, mesopores 2–50nm, and macropores >50nm. Glycerol, alcohol, and sucrose have different molecular weights that can block different pore openings, improving the sealing effect.

[0041] Third, because the gas in the activated carbon particles is at normal pressure, during storage and use, the pressure difference between the inside and outside of the activated carbon is zero, which reduces stress and creates good conditions to avoid the rupture of microbubble particles, further preventing gas loss.

[0042] Embodiment 3: The carbonization furnace in Embodiment 2 can be a carbonization furnace currently purchased on the market, but this type of carbonization furnace is a general type, not designed only for Embodiment 2, and has the characteristics of complex structure and redundant functions. Therefore, a carbonization furnace for use with Embodiment 2 is redesigned. The structure of the carbonization furnace includes a barrel 1 arranged horizontally in the axial direction, a supporting structure is provided at the bottom of the barrel 1, a driving mechanism is provided on the barrel 1, a heating mechanism is provided on the barrel 1, a steel pipe 2 is provided in the axial direction of the barrel 1, the pipe 2 is rotatably connected to the barrel 1, and a vacuum valve 3 and a liquid spray valve 4 are provided at both ends of the pipe 2, respectively. The vacuum valve 3 and the liquid spray valve 4 are both located on the outside of the barrel 1. A plurality of atomizing nozzles 5 are provided at the bottom of the pipeline 2. An inlet and outlet port 6 is provided at one end of the barrel 1. When feeding and discharging, the inlet and outlet port 6 is exposed. At other times, the inlet and outlet port 6 is blocked with a sealing cover. The inlet and outlet port 6 is close to the inner wall of the barrel 1. A screw 7 is provided in the barrel 1. The screw 7 is close to the inner wall of the barrel 1. One end of the screw 7 is close to the inlet and outlet port 6 and is rotatably connected to the barrel 1. The other end of the screw 7 extends out of the barrel 1 and is connected to a first motor 8. The output end of the first motor 8 is fixed to the screw 7, and the casing of the first motor 8 is fixed to the barrel 1.

[0043] On the outer sides of both ends of the barrel 1, counterweights 9 are provided. The counterweights 9 are connected to the pipeline 2 through connecting rods 10, and the connecting rods 10 are detachably connected to the pipeline 2, such as screw connection. On the inner wall of the barrel 1, a plurality of stirring plates 24 are provided, and the longitudinal direction of the stirring plates 24 is parallel to the axial direction of the barrel 1. Figure 1 Only part of the stirring plates 24 are shown in the figure.

[0044] There are two support structures. The two support structures are respectively close to both ends of the barrel 1. The support structure includes support wheels 11 respectively located on both sides of the bottom of the barrel 1. The support wheels 11 are connected to the ground through the first brackets 12, and the support wheels 11 are rotatably connected to the first brackets 12.

[0045] The driving mechanism includes a second motor 13 located below the barrel 1. The second motor 13 is connected to the ground through a second bracket 14. A gear 15 is provided at the output end of the second motor 13, and a gear ring 16 is meshed with the upper side of the gear 15. The gear ring 16 is fixed to the barrel 1.

[0046] The heating mechanism includes a sleeve 17 located outside the barrel 1. An incineration chamber 18 is formed between the sleeve and the barrel 1. A plurality of flame nozzles 19 are provided in the incineration chamber 18. The flame nozzles 19 are connected to a natural gas supply source through a gas pipeline. Baffles 20 connecting the barrel 1 are provided at both ends of the sleeve 17. An air inlet hole 21 is provided on one of the baffles 20, and a smoke exhaust port 22 is provided on the other baffle 20. The baffle 20 is rotatably connected to the barrel 1. The barrel 1 is connected to the ground through a third bracket 23.

[0047] Working principle: Start the second motor 13. The second motor 13 drives the gear 15 to rotate. The gear 15 drives the barrel 1 to rotate through the gear ring 16 until the feeding and discharging port 6 is at a high position. Stop the second motor 13. Activated carbon particles enter the barrel 1 from the feeding and discharging port 6 and block the feeding and discharging port 6.

[0048] Start the second motor 13 to keep the barrel 1 rotating at a speed of 10 - 20 revolutions per minute. Since the pipeline 2 is connected with the counterweight 9, the pipeline 2 does not rotate with the barrel 1, so that the atomizing nozzle 5 always remains downward.

[0049] The vacuum valve 3 is connected to a vacuum device, and the liquid spraying valve 4 is connected to a liquid spraying device (such as a pump). Close the liquid spraying valve 4, open the vacuum valve 3, start the vacuum device, and the air in the barrel 1 is discharged through the atomizing nozzle 5, the pipeline 2 and the vacuum valve 3, so that the inside of the barrel 1 is in a vacuum state and maintained for about 10 minutes, and the air in the activated carbon particles can be smoothly discharged.

[0050] Close the vacuum valve 3 and connect the vacuum valve 3 to a gas supply device, such as a pressure vessel filled with sulfur hexafluoride, perfluoropropane, or perfluorobutane. The pressure vessel is connected to the vacuum valve 3 through a pressure reducing valve. Open the vacuum valve 3 to allow the gas to enter the barrel 1 at atmospheric pressure and keep it for 10 - 20 minutes to fill the pores of the activated carbon particles with gas.

[0051] Natural gas goes from the flame nozzle 19 into the incineration chamber 18. An igniter can be set at the flame nozzle 19 to ignite the natural gas. The natural gas burns in the incineration chamber 18 to raise the temperature in the barrel 1 to 650 - 700 °C. The smoke outlet 22 is connected to a smoke exhaust pipe to lead out the flue gas. The air inlet hole 21 is connected to a blower through an air inlet pipe to supply oxygen to the incineration chamber.

[0052] Close the vacuum valve 3, open the liquid spraying valve 4, and start the liquid spraying device. The pore - closing solution slowly sprays out through the pipeline 2 and the atomizing nozzle 5, adheres to the activated carbon particles, and carbonizes into carbon molecules at high temperature to block the pores of the activated carbon particles. After spraying the pore - closing solution, keep it warm for more than 5 minutes, stop supplying natural gas to the carbonization furnace, and the carbonization furnace stops heating. Stop the second motor 13 when the feeding and discharging port 6 is at a low position. After the furnace cools down, take out the activated carbon particles. When taking them out, first open the feeding and discharging port 6, then start the first motor 8. The first motor 8 drives the screw rod 7, and the activated carbon particles are discharged from the feeding and discharging port 6.

[0053] The carbonization furnace of Example 3 has the characteristics of simple structure and low cost, and is also relatively convenient to use.

Claims

1. A microbubble particle for gastrointestinal ultrasound detection, characterized in that: The invention comprises activated carbon particles, the pores of which are filled with gas, the gas material of which is sulfur hexafluoride, perfluoropropane or perfluorobutane, and a shell is arranged on the outer side of the activated carbon particles.

2. The microbubble particles for gastrointestinal ultrasound detection according to claim 1, characterized in that: The gas material is perfluorobutane.

3. The microbubble particles for gastrointestinal ultrasound detection according to claim 1, characterized in that: The activated carbon particles have a fineness of 150-220 meshes.

4. The production process of microbubble particles according to claim 1, 2 or 3, characterized in that: It includes the following steps: a. Put the activated carbon particles into the carbonization furnace, and evacuate the carbonization furnace to discharge the air in the activated carbon particles; b. Inject gas into the carbonization furnace until the gas pressure in the carbonization furnace reaches the standard atmospheric pressure, so that the pores of the activated carbon particles are filled with gas under the standard atmospheric pressure; c. The carbonization furnace is heated to 650-700°C, and an atomized closed-cell solution is sprayed into the carbonization furnace. The closed-cell solution includes glycerol, alcohol and sucrose. After the closed-cell solution is sprayed, the temperature is kept for more than 5 minutes. After the carbonization furnace is cooled, the activated carbon particles are taken out; d. A shell is coated on the outside of the activated carbon particles.

5. The production process of microbubble particles according to claim 4, characterized in that: In the step a, the carbonization furnace rotates when vacuuming; in the step b, the carbonization furnace rotates when gas is injected into the carbonization furnace; in the step c, the carbonization furnace rotates when atomized closed-cell solution is sprayed into the carbonization furnace.

6. The production process of microbubble particles according to claim 4, characterized in that: In the step c, the weight of the sprayed closed-cell solution is 5%-10% of the weight of the activated carbon particles in the carbonization furnace.

7. The production process of microbubble particles according to claim 4, characterized in that: The ratio of glycerol, alcohol and sucrose in the closed-cell solution is 1:2:

1.

8. The production process of microbubble particles according to claim 4, characterized in that: The structure of the carbonization furnace comprises a barrel (1) arranged horizontally in an axial direction, a supporting structure is arranged at the bottom of the barrel (1), a driving mechanism is arranged on the barrel (1), a heating mechanism is arranged on the barrel (1), a pipeline (2) is arranged in the axial direction of the barrel (1), the pipeline (2) is rotatably connected to the barrel (1), a vacuum valve (3) and a liquid spray valve (4) are respectively arranged at both ends of the pipeline (2), the vacuum valve (3) and the liquid spray valve (4) are both located on the outside of the barrel (1), a plurality of atomizing nozzles (5) are arranged at the bottom of the pipeline (2), an inlet and outlet (6) is arranged at one end of the barrel (1), the inlet and outlet (6) is close to the inner wall of the barrel (1), a screw (7) is arranged in the barrel (1), the screw (7) is close to the inner wall of the barrel (1), one end of the screw (7) is close to the inlet and outlet (6), and the other end of the screw (7) extends out of the barrel (1) and is connected to a first motor (8).

9. The production process of microbubble particles according to claim 4, characterized in that: A counterweight block (9) is provided on the outer side of the barrel (1), and the counterweight block (9) is connected to the pipeline (2) via a connecting rod (10), and the connecting rod (10) and the pipeline (2) are detachably connected.

10. The production process of microbubble particles according to claim 4, characterized in that: There are two support structures, the two support structures are respectively close to the two ends of the barrel (1), and the support structures include support wheels (11) respectively located on both sides of the bottom of the barrel (1), the support wheels (11) are connected to the ground through a first bracket (12), and the support wheels (11) are rotatably connected to the first bracket (12); The driving mechanism comprises a second motor (13) located below the barrel (1), the second motor (13) being connected to the ground via a second bracket (14), a gear (15) being provided at the output end of the second motor (13), a gear ring (16) being meshed on the upper side of the gear (15), and the gear ring (16) being fixed to the barrel (1); The heating mechanism comprises a sleeve (17) located outside the barrel (1), a combustion chamber (18) is formed between the sleeve and the barrel (1), a plurality of flame nozzles (19) are arranged in the combustion chamber (18), baffles (20) connected to the barrel (1) are arranged at both ends of the sleeve (17), one of the baffles (20) is provided with an air inlet hole (21), and the other baffle (20) is provided with a smoke exhaust port (22), the baffle (20) is rotatably connected to the barrel (1), and the barrel (1) is connected to the ground via a third bracket (23).

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