CN201033178Y - A Novel Extracorporeal Artificial Liver Support Therapy System - Google Patents

Abstract

A new type of extracorporeal artificial liver support treatment system, including an extracorporeal blood circulation circuit and an albumin solution circulation circuit, characterized in that: the treatment system also includes a replacement fluid pipeline, and the replacement fluid pipeline includes a replacement fluid container [8], the replacement liquid cavity of the ultrafiltrate container [9] and the second dialyzer [6]; the outlet [10] of the replacement liquid cavity of the second dialyzer [6] is connected to the ultrafiltrate container [9] and the outlet of the replacement fluid container [8] is connected to the albumin solution circulation line or the blood circulation line. The utility model adopts filtration or dialysis filtration to remove toxins in protein circulation, more effectively and thoroughly removes middle molecular substances (including molecular inflammatory factors), and improves curative effect.

Description

A Novel Extracorporeal Artificial Liver Support Therapy System

technical field

The utility model relates to a medical device, in particular to a temporary and partial replacement of liver function, removing various toxins and toxic metabolites including protein-bound toxins and water-soluble toxins, so as to treat hepatic insufficiency, liver failure or related diseases. An extracorporeal artificial liver support system for disease.

Background technique

Severe hepatitis/liver failure is severe liver damage caused by various factors, leading to serious impairment or decompensation of its synthesis, detoxification, excretion, and biotransformation functions, with coagulation mechanism disorders, jaundice, hepatic encephalopathy, and ascites as symptoms. The main performance of a group of clinical syndrome, the mortality rate as high as 60 to 80%. The main methods for the treatment of this disease are comprehensive medical treatment, artificial liver support treatment and liver transplantation. Among them, extracorporeal artificial liver support refers to a treatment method that removes various harmful substances, supplements essential substances, and regulates the internal environment through mechanical, physical, chemical, or biological devices outside the body. Based on the strong regenerative ability of the liver, it temporarily replaces part of the function of the failed liver. , Can create conditions for liver cell regeneration and recovery of liver function or wait for the opportunity for liver transplantation.

The artificial liver support system is divided into three types: non-biological type, biological type and combined type. Non-biological artificial liver has been widely used clinically and has been proven to have certain curative effect. Non-biological artificial liver methods include plasma exchange (PE), hemoperfusion (HP), hemofiltration (HF), hemodialysis (HD), molecular adsorption recirculation system (MARS), Albumin Adsorption Recirculation System (PARS), etc. The biological type and combined biological artificial liver support system are still in the research stage.

Among the non-biological artificial liver treatment systems, the more advanced ones are the molecular adsorption recirculation system (MARS) and the albumin adsorption recirculation system (PARS). , which has the significant advantage of being able to simultaneously remove protein-bound toxins and water-soluble toxins. Albumin adsorption and recirculation system (PARS), the specific structure can refer to the Chinese patent announcement published on August 30, 2006, the application date is June 22, 2005, and the name is "A kind of in vitro artificial liver support system". New patents. The patent scheme discloses that the albumin adsorption recirculation system is composed of three circuits: an extracorporeal blood circulation circuit, an albumin circulation circuit and a dialysate circulation circuit.

Although the albumin adsorption and recirculation system (PARS) disclosed in the above-mentioned patent scheme has a certain removal effect on small-molecule protein-bound toxins and water-soluble toxins, its removal effect on middle-molecule toxins (including inflammatory factors) is still not good. At present, it is believed in medicine that the pathogenesis of severe hepatitis is mainly due to the further necrosis of liver cells caused by the super-strong immune response induced by endotoxin with tumor necrosis factor as the core. Therefore, if the artificial liver support system can more effectively remove various Medium molecular inflammatory factors can more effectively block the inflammatory cascade reaction induced by endotoxin with tumor necrosis factor as the core, and block the vicious circle of continuous progression in patients with severe hepatitis/liver failure.

Contents of the invention

The utility model provides a new type of extracorporeal artificial liver support treatment system for overcoming the poor effect of removing various middle molecular toxins (including middle molecular inflammatory factors) in the patient's body existing in the prior art, which can remove, While small molecule protein binds toxins and water-soluble toxins, it can more effectively filter out medium molecule toxins (including medium molecule inflammatory factors), and at the same time make albumin have greater capacity and activity to remove various protein-bound toxins, and can It can more comprehensively and effectively remove various toxins in the body, more effectively block the inflammatory cascade reaction induced by endotoxin with tumor necrosis factor as the core, and block the vicious cycle of continuous progression in patients with severe hepatitis/hepatic failure. Cell regeneration creates more favorable conditions and improves the success rate of severe hepatitis/liver failure rescue.

In order to achieve the above purpose, the technical solution adopted by the utility model is: a new type of extracorporeal artificial liver support treatment system, including an extracorporeal blood circulation pipeline and an albumin solution circulation pipeline, and the input end to the output of the extracorporeal blood circulation pipeline A blood pump, a blood chamber of the first dialyzer and a safety valve are sequentially connected between the ends; the albumin liquid circulation pipeline mainly consists of the albumin chamber of the first dialyzer, the albumin chamber of the second dialyzer and the The liquid pumps are connected in series to form a circulation loop; its innovation points are:

The treatment system also includes a replacement fluid pipeline, which includes an ultrafiltrate container, a replacement fluid container, and a replacement fluid chamber of the second dialyzer; the outlet of the replacement fluid chamber of the second dialyzer is connected to The ultrafiltrate container; and the outlet of the replacement fluid container is connected to the albumin solution circulation line or the blood circulation line.

The relevant content in the above-mentioned technical scheme is explained as follows:

1. In the above scheme, the flow of the replacement fluid in the replacement fluid pipeline can be automatically circulated due to potential energy difference or pressure difference, or it can be driven by a pump as a power to circulate, and a throttle can be installed in the pipeline to ensure: The amount of replacement liquid flowing out of the replacement liquid container is equal to the amount of liquid flowing into the ultrafiltrate container to achieve the balance of the amount of liquid in and out. similar structure.

3. In the above solution, the outlet of the replacement fluid container is also connected to the inlet of the replacement fluid chamber of the second dialyzer, thereby constituting a dialysis filtration mechanism and further improving the ability to remove toxins.

4. In the above scheme, the sentence "the outlet of the replacement fluid container is connected to the albumin solution circulation pipeline or the blood circulation pipeline" means that the outlet of the replacement fluid container can be connected to the albumin solution circulation pipeline Or at any point or multiple points on the blood circulation pipeline, among which there are the following three preferred solutions: a. The outlet of the replacement fluid container is connected to the albumin cavity inlet of the second dialyzer in the albumin solution circulation pipeline b. The outlet of the replacement fluid container is connected to the outlet of the albumin cavity of the second dialyzer in the albumin solution circulation pipeline; c. The outlet of the replacement fluid container is connected to the first dialyzer in the blood circulation pipeline. The entrance to the blood chamber of a dialyzer.

5. In the above solution, an activated carbon adsorption column, an anion exchange resin adsorption column and similar devices capable of adsorbing and regenerating albumin are also connected in series in the albumin liquid circulation pipeline.

6. In the above scheme, a volume regulator is connected in series in the albumin liquid circulation pipeline, which is specifically a container with an adjustable volume, and the inner cavity of the container is connected in series with the albumin liquid circulation pipeline, so that By adjusting the volume regulator, the total volume of the entire albumin liquid circulation pipeline can be adjusted, and at the same time, the effect of adjusting the concentration of albumin in the albumin liquid circulation pipeline is also achieved. Preferably, the volume regulator is also equipped with a concentration detector, which can display the albumin concentration in the pipeline in real time, so as to facilitate adjustment by medical staff.

7. In the above scheme, in the blood circulation pipeline, a blood pipeline defoamer is connected in series between the blood pump and the blood chamber inlet of the first dialyzer, and a blood pipeline defoamer is connected in series between the blood chamber outlet of the first dialyzer and the safety valve. There is a vascular funnel.

8. In the above scheme, in the albumin solution circulation pipeline, a blood leakage monitor is connected to the outlet of the albumin chamber of the first dialyzer.

9. In the above solution, the albumin solution pipeline defoamer is also connected in series in the albumin solution circulation pipeline.

10. In the above scheme, a heater is provided beside the replacement fluid container or at the outlet of the replacement fluid container, so as to heat the replacement fluid and make the patient feel more comfortable during use.

11. In the above solution, the "first dialyzer" must use a high-flux dialyzer, and the "second dialyzer" also uses a high-flux dialyzer. The dialyzer is prior art, and it generally has two independent cavities separated by a semi-permeable membrane. One cavity of the first dialyzer passes blood, which is called the blood cavity, and the other cavity passes albumin solution, which is named the albumin cavity. One cavity of the second dialyzer passes through the albumin solution, which is called the albumin cavity, and the other cavity passes through the replacement fluid, which is named the replacement solution cavity.

The first dialyzer and the second dialyzer are selected according to the following principles:

The first dialyzer needs to ensure that the protein-bound toxins and water-soluble toxins of small and medium molecules in the blood can enter the albumin circulation through its semi-permeable membrane in the form of diffusion or convection, while the beneficial substances such as cell components and macromolecular proteins in the blood Cannot pass through its semipermeable membrane.

The second dialyzer needs to ensure that small and medium-sized protein-binding toxins and water-soluble toxins in the albumin solution can be filtered through its semi-permeable membrane smoothly by diffusion or convection, while albumin cannot pass through its semi-permeable membrane.

The material of the semipermeable membrane of described first dialyzer and the second dialyzer comprises; Polysulfone, polyacrylonitrile, polyamide, polyacetate cellulose etc., the material and structure of membrane need to meet the following conditions: 1, have better 2. The molecular weight cut-off is clear, so that small and medium molecular substances can pass through smoothly, and macromolecular substances such as proteins and cell components cannot pass through. 66000Da, the permeability of protein molecules in blood is generally controlled at 0.1, the best is 0.01 or less; 3. The membrane wall is thin enough, the general wall thickness is 50m, the better wall thickness is 40m, and the best wall thickness is 30m or less Thinner, with high water molecule permeability and high filtration rate, various protein binding and water-soluble small and medium toxic substances can pass freely; the membrane area is large enough, the general surface area is 1m ² and the best area is 2m ² ; 4. No It is easy to attach protein, so as not to form a covering film and affect the filtration rate; 5. The physical properties are stable.

12. In the above scheme, the replacement fluid can be the replacement fluid commonly used in existing hemofiltration and hemofiltration dialysis. The composition of the replacement fluid should be basically the same as that of normal human extracellular fluid, and it should be absolutely sterile and free of pyrogens. For special patients, appropriate adjustments can also be made according to their specific internal environment.

The design principle of the present utility model is: the present utility model improves the removal of water-soluble toxins by adopting the dialysis method in the albumin adsorption cycle of the prior art to the removal by the filtration method or the dialysis filtration method, because the existing theory proves that: Convection is used to remove water-soluble toxins, while dialysis is used to remove water-soluble toxins through dispersion. Compared with the two, the ability of the two to remove small molecular substances is basically equal, while for medium molecular substances (including medium Molecular inflammatory factors), filtration has obvious advantages. And dialysis filtration combines the characteristics of dialysis and filtration, and the effect is better.

Therefore, the utility model has the following advantages compared with the prior art:

1. At the same time, because this utility model adopts filtration or diafiltration to remove water-soluble toxins in the albumin solution in the albumin circulation pipeline, the activity of albumin is enhanced, the adsorption capacity is improved, and the adsorption capacity is increased, so that the albumin The liquid can take away more protein-bound toxins from the patient's blood, further improving the therapeutic effect.

2. Since the utility model uses filtration or diafiltration to remove water-soluble toxins in the albumin solution in the albumin circulation pipeline, the middle molecular substances (including middle molecular inflammatory factors) in the albumin solution Clear more thoroughly, so as to more effectively block the inflammatory cascade reaction induced by endotoxin with tumor necrosis factor as the core, block the vicious cycle of continuous progression in patients with severe hepatitis/liver failure, and at the same time have immune regulation, improve The effect of many aspects such as the patient's internal environment can effectively improve the therapeutic effect.

Description of drawings

Accompanying drawing 1 is a schematic diagram of a circulation pipeline of the utility model embodiment;

Accompanying drawing 2 is the schematic diagram of the second circulation pipeline of the utility model embodiment;

Accompanying drawing 3 is the schematic diagram of the three-circulation pipeline of the utility model embodiment;

Accompanying drawing 4 is the schematic diagram of the fourth circulation pipeline of the utility model embodiment.

In the above drawings: 1. input terminal; 2. output terminal; 3. blood pump; 4. first dialyzer; 5. safety valve; 6. second dialyzer; 7. albumin solution pump; 8. replacement fluid Container; 9, ultrafiltrate container; 10, the outlet of the second dialyzer replacement liquid chamber; 11, the inlet of the second dialyzer replacement liquid chamber; 12, the first dialyzer blood chamber inlet; 13, the first dialyzer blood chamber Cavity outlet; 14. The first dialyzer albumin chamber inlet; 15. The first dialyzer albumin chamber outlet; 16. The second dialyzer albumin chamber inlet; 17. The second dialyzer albumin chamber outlet; 18. Activated carbon Adsorption column; 19. Anion exchange resin adsorption column; 20. Volume regulator; 21. Blood pipeline defoamer; 22. Blood vessel funnel; 23. Blood leakage monitor; 24. Albumin solution pipeline defoamer; 25 , Liquid inlet pump; 26, Liquid discharge pump.

Detailed ways

Below in conjunction with accompanying drawing and embodiment the utility model is further described:

Embodiment 1: Referring to Figure 1, a new type of extracorporeal artificial liver support treatment system is composed of three parts: an extracorporeal blood circulation circuit, an albumin solution circulation circuit and a replacement fluid circuit.

Referring to the accompanying drawing 1, in the extracorporeal blood circulation circuit, the input end 1 is connected to the blood cavity inlet 12 of the first dialyzer 4 through the blood pump 3 and the blood line defoamer 21 through the artificial liver dedicated pipeline. , the blood cavity outlet 13 of the first dialyzer 4 is connected to the output port 2 through the blood vessel funnel 22 and the safety valve. The blood flow in the blood chamber of the first dialyzer 4 is from top to bottom as shown in the figure.

Referring to shown in accompanying drawing 1, in described albumin liquid circulating line, be to use the artificial liver special pipe to pass the outlet 15 of the albumin chamber of the first dialyzer 4 successively through blood leakage monitor 23, albumin liquid pump 7, The albumin solution pipeline defoamer 24 is connected to the albumin chamber inlet 16 of the second dialyzer 6 , and the albumin chamber outlet 17 is connected to the albumin chamber inlet 14 of the first dialyzer 4 through the volume regulator 20 . The above-mentioned volume regulator 20 is connected to the albumin liquid circulation pipeline, and the volume regulator 20 is directly equipped with a concentration detector. When in use, the overall volume of the pipeline can be adjusted by adjusting the volume regulator 20, so as to achieve the adjustment of the pipeline. The effect of the concentration of albumin in the solution. The flow direction of the albumin solution in the albumin cavity of the first dialyzer 4 is as shown in the figure, which is from bottom to top, which can ensure the best effect.

Referring to shown in accompanying drawing 1, described replacement fluid pipeline is composed of replacement fluid container 8, ultrafiltrate container 9, the replacement fluid chamber of second dialyzer 6, inlet pump 25 and drain pump 26; The second dialyzer The outlet 10 of the replacement liquid chamber of 6 is connected to the ultrafiltrate container 9 through the drain pump 26; and the outlet of the replacement liquid container 8 is connected to the albumin of the second dialyzer in the albumin solution circulation line through the liquid inlet pump 25 16 at the entrance of the protein cavity. When in use, the replacement liquid enters the albumin liquid circulation line from the replacement liquid container 8 and circulates, and the medium and small molecular substances in the albumin liquid are filtered out to the ultrafiltrate container 9 by means of ultrafiltration through the second dialyzer 6 Among them, an albumin adsorption filtration system is formed.

In the present embodiment, the liquid inlet pump 25 and the liquid discharge pump 26 are used to balance the amount of liquid in and out, and ensure that the amount of replacement liquid supplied by the replacement liquid container 8 to the system is equal to the amount of ultrafiltrate discharged from the system.

In this embodiment, a heater can be attached to the replacement fluid container 8, and the replacement fluid can be heated by the heater to make the replacement fluid reach a comfortable temperature accepted by the human body, so that the patient feels more comfortable during treatment.

The first dialyzer 4 used in this embodiment is an HF1200 dialyzer from Baxter, and the second dialyzer 6 is a Fresenius AV600 dialyzer.

The replacement fluid in this embodiment is bicarbonate replacement fluid. In order to achieve individualized treatment, it should also be adjusted according to the specific situation of the patient.

The basic formula of the replacement fluid:

Element General content (mmol/L) Optimum content (mmol/L) K+ 0～4 3.0～3.5 Na+ 138～150 135～140 Cl- 100.7～125 100～115 Bicarbonates 32～38 105～110 Ca+ ^* 1.62～3.5 2.0～3.0 Mg+ ^* 0.75～1.5 0.4～0.6

Note: *Ca+ and Mg+ should be supplemented from another channel when carbonate is selected to avoid the formation of precipitates.

In this embodiment, a certain concentration of albumin is used to form the albumin cycle, and albumin can compete for binding to remove various protein-binding toxins in the patient's body. Currently, protein-binding toxins that can be isolated include bilirubin, cholic acid, short- and medium-chain fatty acids, aromatic fatty acids, thiols, nitric oxide, blood ammonia, tryptophan, indole and phenolic metabolites.

In this embodiment, the protein concentration in the protein circulation and the amount of liquid in the circulation can be adjusted in a wide range according to the needs, and the operation is very convenient. Generally speaking, the concentration range of albumin is 1-50 g/L, and the preferred concentration is 4.0-40 g/ml.

Preparation of albumin solution:

Specific method: Dissolve 12 sticks of 20% human albumin in 50 milliliters in 500 milliliters of replacement fluid.

The specific operation is as follows:

1. Turn on the power; turn on the power switch;

2. Connect the pipeline as shown in the figure;

3. Use replacement fluid to prefill and exhaust the blood circulation pipeline and albumin circulation pipeline. The prefill time is 15 minutes, and the prefill temperature is 20°C;

4. Start the treatment; open the blood, albumin circulation and the passage of replacement fluid. First connect the albumin solution to the replacement fluid inlet, inject all the albumin into the albumin circulation (the volume and concentration of the protein in the circulation can be adjusted through the protein circulation volume regulator according to the specific situation), and then connect the replacement fluid to the replacement fluid The entrance, the treatment begins. Set the simulated flow rate of plasma to 180ml/L, the flow rate of albumin to 250ml/L, the flow rate of the replacement fluid in and out to 50ml/L, set a heparin cap for extracorporeal blood circulation, and supplement heparin to prevent blood coagulation.

5. The single treatment time is 4 to 8 hours. After stopping the machine, disconnect the connection between the pipeline and the patient's vein.

Embodiment 2: Referring to Figure 2, a new type of extracorporeal artificial liver support treatment system is composed of three parts: an extracorporeal blood circulation circuit, an albumin solution circulation circuit and a replacement fluid circuit. It differs from Embodiment 1 in that: the replacement fluid container 8 is not connected to the albumin chamber inlet 16 of the second dialyzer via the liquid inlet pump 25, but is connected to the albumin chamber outlet of the second dialyzer 17 on. Others are the same as those in Embodiment 1, and will not be repeated here.

Embodiment 3: Referring to the accompanying drawing 3, a new type of extracorporeal artificial liver support treatment system is composed of three parts: extracorporeal blood circulation pipeline, albumin solution circulation pipeline and replacement fluid pipeline. It differs from Embodiment 1 in that the replacement fluid container 8 is not connected to the albumin cavity inlet 16 of the second dialyzer via the liquid inlet pump 25, but is connected to the first dialyzer in the blood circulation circuit. The blood chamber inlet 15 of the device 4; and, between the albumin chamber outlet 17 of the second dialyzer 6 and the volume regulator 20, an activated carbon adsorption column 18 and an anion exchange resin adsorption column 19 are sequentially connected in series. The activated carbon adsorption column 18 and the anion exchange resin adsorption column 19 are used to perform toxin adsorption and regeneration on the albumin liquid in the albumin circulation pipeline, so as to further improve the toxin removal effect.

Embodiment 4: Referring to Figure 4, a new type of extracorporeal artificial liver support treatment system is composed of three parts: an extracorporeal blood circulation circuit, an albumin solution circulation circuit and a replacement fluid circuit. It differs from Embodiment 1 in that the replacement fluid container 8 is not connected to the albumin chamber inlet 16 of the second dialyzer through the inlet pump 25, but the replacement fluid container 8 is divided into two via the inlet pump 25. One way is connected to the inlet 11 of the replacement fluid chamber of the second dialyzer 6, and the other is connected to the outlet 17 of the albumin chamber of the second dialyzer 6 in the albumin circulation line, so that one way of replacement fluid (as shown in the figure) (shown) flows through the replacement liquid chamber of the second dialyzer 6 from bottom to top, and another replacement liquid flows into the albumin circulation pipeline to circulate with the albumin, and completes dialysis and filtration at the same time, forming a diafiltration system. Moreover, an activated carbon adsorption column 18 and an anion exchange resin adsorption column 19 are sequentially connected in series between the albumin chamber outlet 17 of the second dialyzer 6 and the volume regulator 20 . The activated carbon adsorption column 18 and the anion exchange resin adsorption column 19 are used to perform toxin adsorption and regeneration on the albumin liquid in the albumin circulation pipeline, so as to further improve the toxin removal effect.

The above-mentioned embodiments are only to illustrate the technical concept and characteristics of the present utility model, and its purpose is to enable those familiar with this technology to understand the content of the present utility model and implement it accordingly, and not to limit the protection scope of the present utility model. All equivalent changes or modifications made according to the spirit of the utility model shall fall within the protection scope of the utility model.

Claims (10)

1. a novel external artificial rami hepatici is held therapy system, comprise extracorporeal circulation of blood pipeline and albumin liquid circulation line, the input of described extracorporeal circulation of blood pipeline [1] is to blood chamber that is serially connected with blood pump [3], first dialyser [4] between outfan [2] successively and relief valve [5]; Described albumin liquid circulation line mainly is connected into closed circuit by the albumin chamber of first dialyser [4], the albumin chamber and the albumin liquid pump [7] of second dialyser [6]; It is characterized in that:

Described therapy system also comprises the displacement liquid pipeline, comprises the displacement sap cavity of ultrafiltrate vessel [9], displacement liquid container [8] and second dialyser [6] in this displacement liquid pipeline; The outlet [10] of the displacement sap cavity of described second dialyser [6] connects ultrafiltrate vessel [9]; And the outlet of described displacement liquid container [8] is connected in the albumin liquid circulation line or in the blood circulation pipeline.

2. a kind of novel external artificial rami hepatici according to claim 1 is held therapy system, and it is characterized in that: the inlet [11] of the displacement sap cavity of second dialyser is also connected in the outlet of described displacement liquid container [8], constitutes dialysis filtration mechanism with this.

3. a kind of novel external artificial rami hepatici according to claim 1 is held therapy system, it is characterized in that: the outlet of described displacement liquid container [8] is connected in the albumin chamber inlet [16] of second dialyser in the albumin liquid circulation line and locates.

4. a kind of novel external artificial rami hepatici according to claim 1 is held therapy system, it is characterized in that: the outlet of described displacement liquid container [8] is connected in the albumin chamber outlet [17] of second dialyser in the albumin liquid circulation line and locates.

5. a kind of novel external artificial rami hepatici according to claim 1 is held therapy system, it is characterized in that: also be serially connected with active carbon adsorption column [18] and anion exchange resin adsorption column [19] in the described albumin liquid circulation line.

6. a kind of novel external artificial rami hepatici according to claim 1 is held therapy system, it is characterized in that: also be serially connected with volume governor [20] in the described albumin liquid circulation line, it is specially the container of a volume adjustable, and the inner chamber string of this container is in albumin liquid circulation line.

7. a kind of novel external artificial rami hepatici according to claim 1 is held therapy system, it is characterized in that: in the described blood circulation pipeline, string has transducer potector bubble trap [21] between the blood chamber inlet [12] of the blood pump [3] and first dialyser, and string has vascular funnel [22] between the blood chamber outlet [13] of first dialyser and the relief valve [5].

8. a kind of novel external artificial rami hepatici according to claim 1 is held therapy system, it is characterized in that: in the described albumin liquid circulation line, the outlet [15] in the described first dialyser albumin chamber locates to be connected to blood leakage monitor [23].

9. a kind of novel external artificial rami hepatici according to claim 1 is held therapy system, it is characterized in that: also be serially connected with albumin liquid pipeline bubble trap [24] in the described albumin liquid circulation line.

10. a kind of novel external artificial rami hepatici according to claim 1 is held therapy system, it is characterized in that: described displacement liquid container [8] exit other or displacement liquid appearance [8] also is provided with constant temperature heating device.

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