KR20030073296A - Blower for manufacturing microcapsules - Google Patents

Abstract

PURPOSE: A blower for manufacturing microcapsule is provided to fabricate microcapsule for cell therapy used for medical purpose in order to treat human being by using it in the human being. CONSTITUTION: The blower for manufacturing microcapsule comprises a solution pipe(1) through which a mixed solution of microcapsule composing constituents and cell suspension passes; a main body(3) through which blowing gas for spraying the mixed solution passes; a fixture(4) installed inside the main body(3) to fix an outer exit(5) of the solution pipe(1) to the center of an outer gas discharge port(7); and a blower support(14) for supporting the microcapsule manufacturing blower, wherein the solution pipe(1) is passes through the center of the fixture(4) fixed adjacently to main body convergence part(8) positioned in the inner lower part of the main body(3) by penetrating an upper part(13) of the main body(3) through which gas passes in such a way that the outer exit(5) of the solution pipe(1) is installed at the central part of the outer gas discharge port(7), wherein gas non-harmful to cells used for spraying the mixed solution of microcapsule composing constituents and cell suspension is injected through a gas injection port(2) of the main body(3), and the gas is sprayed to the mixed solution as the gas is being blown through the outer gas discharge port(7) positioned at the lower center of the main body(3), wherein the fixture(4) is fixed adjacently to a lower convergence part(8) inside the main body(3) of the microcapsule manufacturing blower and fixes the solution pipe(1) in such a way that the solution pipe(1) passes through a small hole at the center of the main body(3), and the outer exit(5) of the solution pipe(1) is positioned in the center of the gas discharge port(7), and wherein the blower for manufacturing microcapsule further comprises a supporting stand(14) which is equipped with support(9), and to which the main body(3) of the microcapsule manufacturing blower is suspended.

Description

Blower for manufacturing microcapsules {omitted}

The international weekly Time (TIME, May 22, 2000, 42) is one of the most promising occupations of the 21st century, holding tissue engineering. This tissue engineering began with the notion of regenerative-restore medicine in tissues, which is divided into several fields. One of them is cell therapy using microcapsule (細胞 治療, cell therapy). Treatment with this microcapsule enables xenograft of cells.

Any organ function essential to the survival of a person is severely deteriorated or deteriorated for some acquired reason, such as end-stage renal failure, or fails to perform its organ-specific function, or it is inherently a problem with an organ's function. In most cases, the organ of a new person to replace the organ must be implanted into the patient or a mechanical artificial organ can be used to replace the function of the original organ.

The general transplantation in the current practice is to donate and transplant other organs, but it is very limited. There are two main reasons for this: First, the number of donors to donate organs is very limited, while the number of beneficiaries who want and receive organs is absolutely absent. Due to the large number of people, most patients cannot get organ transplants because supply and demand do not match. Second is the immunological problem. The transplantation of other organs does not match histocompatibility, which means that many patients who need to be transplanted cannot receive the organ or use the organ due to rejection.

Absolute shortage of transplanted organs to sustain the life of patients with end-stage diseases promotes the functional improvement of existing mechanical artificial organs and regenerates some normal cells of damaged organs or stem cells. The research on artificial organs using tissue engineering using the back has been spurred. That is, in order to solve the problem of human organs, which are absolutely insufficient, histological methods of culturing some cells of a desired organ and reconstituting the organ have begun to be used. However, this method is also difficult to form a three-dimensional tissue to date, and the acquisition of the function is not achieved in practical use in many organs. Many of these terminally ill patients need other special mechanical organs to maintain normal life, but the diseases that can solve this problem with suitable mechanical artificial organs are very limited.

If the tissue engineering method of organ unit is not available, the treatment by the tissue unit method of cell unit is selected. However, xenograft, a method of using animal organs or cells that can replace human organs, may be considered in situations where the donation of cells from another person is not acceptable.

In the case of using the organs or cells of an animal, the number of organs or cells to be provided for treating a human disease, depending on the type of animal, can be obtained almost infinitely compared to the organs of the same kind of human. However, when treating diseases by organ or cell transplantation of animals, histocompatibility due to the antibody reaction of the human body to antigens of animal tissues, Due to histocompatibility problems, the immunological rejection phenomenom causes animal tissues and cells to be rejected and killed by the transplanted person. In other words, treatment with organs or cells of animals fails.

Such xenotransplantation (異 種 臟器 移植) is impossible to use for a long time because of immunological rejection, it is also temporarily used to overcome the extreme situation. In theory, however, this rejection prevents the production of antigens from tissues or cells of the transplanted animal, or the recognition of the antigen in patients transplanted with organs regardless of the production of the animal's antigen, It is a method of inhibiting the production of antibodies or preventing the production of antibodies in the body of a transplant patient. There is no way to prevent transplanted organs from producing antigens. Alternatively, the method of inhibiting antibody production in the body of a transplanted patient is to administer the drug, an immunosuppressive agent, to prevent the expression of the antibody. The other is that the transplanted organ acts as an antigen, but a barrier is formed between the antigen and the immune system of the transplanted patient. ) Does not recognize the antigen, which prevents the production of antibodies.

Many of these methods are theoretically possible, but are very difficult. Currently, transplanting animal organs to the human body is, in fact, recognized by the immune system of the patient receiving the transplanted organ or cell as an antigen. It has been used as a temporary treatment for the use of antibodies against human production until they are produced in humans. In some minority, immunosuppressive administration has been attempted but rarely performed.

In recent years, medical methods have been attempted to prevent antigen-antibody reactions from occurring and to prevent rejection by using a method of isolating transplanted heterologous cell antigens from human antibodies. . How to create a barrier to sequester these antigens and antibodies has been under research for several years, and this technique is called microencapsulation.

Currently, the most frequently studied disease using microcapsules is diabetes. Diabetes caused by lack of insulin due to pancreas islet cells, which is a congenital cause of various subdivided diabetes, This is particularly the therapeutic target. Microencapsulation for the treatment of diabetes in humans is characterized by small pores of smaller size than the size of animal antigen molecules around the pancreatic islet cells of animals, especially pigs. Make a membrane that owns micropore and pass nutrients including oxygen for growth of pancreatic islet cells in animals or insulin produced by pancreas islet cells, but not animal cells Antigens are not allowed to pass through, creating a barrier composed of alginate. Pancreatic islet cells of xenograft-derived animals after collection are continuously supplied in the microcapsule while continually secreting insulin, if only nutrients are continuously supplied. As a result, almost all diabetic patients around the world caused by the lack of insulin have been studied to avoid the uncomfortable treatment of daily injection of insulin for the treatment of diabetes.

In addition, microcapsules, other diseases of the study subjects, except diabetes is a hormone-related deficiency such as growth disorders (成長 에) caused by growth hormone deficiency (缺乏 症). In particular, as in diabetes, when there is an abnormality in hormone production due to an abnormality of hormone secretory cells due to a congenital reason, the hormone secretion cells are collected from an animal other than human and alginate, etc. Microencapsulation is used to make barriers.

At present, the apparatus required to manufacture microcapsules has not been developed and marketed on the market in a certain form in a standardized market, and each research institute is used to make its own coarse, and material and disinfection problems are observed. It also has a number of problems, including the inability to derive research that possesses any standardized repeatability.

Research and development of cell therapy, or microencapsulation, using microcapsules, a subdivision of tissue engineering for the treatment of human diseases, In the treatment of diseases of animals, xenograft is possible using animal cells, and the human cells can be healed by animal cells, which has been the biggest problem in transplantation. Because of the numerical unbalance that has occurred between donors and cell recipients, it is very important that many patients who have undergone most cell transplants have not received decisive treatment. The problem can be solved.

The microcapsule possessing this advantage also has some problems to date.

Firstly, tissue engineering using microcapsules is currently a preclinical study that is being carried out internationally or domestically, in most laboratory studies, or in some animals. As a preclinical study, the use of microcapsules is limited to experimental animals, and the number of study teams doing this research is very limited. The blower used for producing microcapsules at home and abroad does not have a standardized product, and its shape is varied. In particular, for the reason that the blower is experimental, most of the microcapsule blowers are manufactured using a simple plastic or the like. That is, until now, it has not been standardized, and the microcapsules produced in the blower for non-standard microcapsules have different sizes and shapes, and standardized treatment ( No standardization was possible.

Second, because the microcapsules blowers used for experiments are not standardized and are mostly made of plastics, these research-experimental microcapsules blowers are used. Hot-high pressure sterilization was not possible. This was not a big problem in the state of carrying out animal experiment temporarily. However, when treating a disease by directly administering microcapsule to the human body, a high-temperature-high pressure sterilization such as an air blower or blower for manufacturing a microcapsule used for an experiment should be cleaned only with alcohol or the like. If the microcapsule is made for cell therapy using a blower for manufacturing microcapsules for experiments, viruses and some bacteria Because of the inevitable infection, the attempt to perform cell therapy using microcapsules cannot avoid iatrogenic human infection. That is, high-pressure sterilization is possible for cell therapy using microcapsules, and cell therapy using microcapsules should be free from infection.

Third, while forming a barrier that surrounds the cell, it surrounds the transplanted cell, such as alginate, which constitutes a barrier that protects the cell from the immune system of the beneficiary. And a mixture of membrane components and cell suspensions that pass nutrients and substances produced by cells (hormones, etc.) to the outside of the membrane. The outer outlet 5 of the solution tube 1 is not easily located in the center 6 of the gas outlet 7 at the gas outlet 7 through the body 3 through which the gas passes. If the external outlet 5 of the solution tube 1 penetrating the main body 3 through which the gas passes is not located at the central portion 6 of the gas outlet, the gas is discharged from the gas outlet 7. Direction is pushed from the center of the gas outlet to one side (the opposite side to the side where the solution tube external outlet 5 is pushed), and the droplet of the membrane component and the cell suspension liquid solution injected from the solution tube external outlet 5 Dropping direction of the microcapsules) is not bent directly down (直 下方) and bent sideways, the microcapasule falling is also not maintaining the regular circular sphere (sphere) and the size is not the same. That is, since the external outlet 5 of the solution tube is not located at the center of the gas outlet 7, the gas ejection direction is changed, and the size of the microcapsule sprayed and dropped as the direction of the ejected gas is changed. And the shape is not constant. In other words, the size of the micropores, the most important part of the microcapsules, is not constant. Eventually, the micropores may expose the antigen to the outside of the membrane. The antibody to this antigen is generated in the blood of the patient, and the antibody can pass through the membrane, whereby the antigen and the antibody meet each other to generate an antigen-antibody reaction, thereby causing the cells in the microcapsules to undergo immune mechanisms. Due to the attack, the cells die and the cell therapy (細胞 治療) can not achieve the purpose. That is, tissue engineering cell treatment using microcapsules will fail. It is difficult to achieve the solution pipe external outlet 5 in the center of the gas outlet unless the solution pipe 1 is held to the center of the gas outlet near the gas outlet 7. That is, the gas ejection direction must be maintained directly downward from the gas ejection opening 7, so that micropores of a certain size can be maintained, so that microcapsules can be produced successfully. .

As described above, as a technical problem related to a microcapsule manufacturing blower, to manufacture a microcapsule manufacturing blower which solves the above problems is a problem to be achieved in the present invention.

1 is a cross-sectional view of the blower for producing microcapsules of the present invention

2 is a view of the main body observed from the bottom when the solution pipe outer outlet is located in the center of the gas outlet;

3 is a top view of a fixture to be installed inside the body to fix the lower solution tube to the center of the external gas outlet;

<Description of the code | symbol about the principal part of drawing>

1. Solution tube

2. Gas inlet

3. Body through which gas passes

4. Fixture for fixing the lower solution tube, inside the body, to the center of the external gas outlet

5. Outlet of solution pipe

6. Gas outlet including solution pipe outlet at the center

7. External outlet of gas passing through main body

8. Convergence start of the body through which gas passes

9. Support base of blower body

10. Solution tube inlet to be mixed solution

11. Gas inlet to be gas-injected

12. Support inside the main body to support the fixture to fix the lower solution tube to the center of the external gas outlet

13. Through part of solution tube on the upper part of main body through which gas passes

14. Support of blower body

The present invention, the microcapsules blower is developed for the purpose of producing a constant microcapsule (microcapsule) that can be used in the human body, that is, aimed at cell therapy (細胞 治療, cell therapy) used for medical purposes for the treatment of humans It was developed and invented to manufacture microcapsules. For this reason, it owns the following features.

First, since the microcapsules produced by this invention will be used to treat human diseases, the material constituting the invention possesses the following characteristics. First of all, all the materials used in this invention must be rust free. At the same time, all materials used in the manufacture of the present invention must be able to withstand in a circular state without deterioration even under conditions of steam, high pressure and high heat. For this reason, the material used in the present invention is composed of a material that does not rust and can withstand high temperature, high pressure and moisture. At the same time, most of the gases used for blowing air use carbon dioxide or nitrogen which is harmless to the human body. However, even if any kind of gas is used that is harmless to the human body, substances deteriorated by the gas or harmful to the human body are used. It will be produced by a material having the properties to synthesize.

Second, specific features and advantages of this microcapsule manufacturing blower will become more apparent from the following description with reference to the accompanying drawings.

The present invention provides a microcapsule membrane aqueous component and a solution tube (1) through which a cell passes, a body (3) through which gas to be used for blowing is passed, a fixture (4) for fixing a lower solution tube in the center of an external gas outlet, and fine It consists of four parts of a blower support 14 for capsule production. The mixed solution of the cell suspension and the membrane component of the microcapsules, in which the components constituting the membrane of the microcapsules and the cells to be used for the treatment, are floating from the solution tube inlet 10. These mixed solutions are passed through the solution tube (1), sprayed by the gas injected through the gas inlet (2) from the solution outlet outside the outlet 5 to fall in the form of droplets, The solution tube 1 through which the cell suspension flows should be as long as the length of the body 3 through which the gas passes, through which the solution tube will pass. There is a gas inlet 2 at the top of the body 3 through which gas passes, and the amount and speed of gas injected through it will be kept constant by an external device separate from this invention. The gas injected through the gas inlet 2 will pass through the body 3 through which the gas passes, and will be discharged through the circular gas outlet 7 having a diameter of a certain size.

The length of the solution tube 1 through which the mixed solution of the components constituting the membrane and the cell suspension is to be changed depending on the length of the main body 3 through which the gas will pass. Although this length is never long, it is actually produced by the present inventors. As a result, after the solution tube 1 passes through the main body 3 in the upper part 13 of the main body 3 through which the gas passes, the outer end of the solution tube 5 is accurately positioned at the center of the gas outlet 7. It was impossible. In this case, if the solution tube is held so as to pass through the center portion of the gas outlet 7 by a device 4 which fixes the solution tube 2 to the center near the gas outlet 7, it is safe and accurate. The outer outlet 5 of the solution tube 1 passes through the central portions 6 and 7 of the gas outlet, and the size and shape of the produced microcapsules could be kept constant. Near the gas outlet 7, inside the main body 3, near the converging portion 8, a solution tube holder 4 for fixing the solution tube 1 to the center portion is manufactured from the outside and the solution tube fixture By being fixed to the support 12, the solution tube outer outlet 5 is located at the center 6 of the gas outlet 7.

The solution tube 1 and the body 3 through which the gas passes are fixed by the blower support 14, the length of which is determined by the distance between the blower support base 9 and the solution tube outer outlet 5. However, it is developed to maintain a distance that can easily move the container that can collect the microcapsules produced through the solution pipe external outlet (5).

As described above, the blower for producing a microcapsule is one of the fields of tissue engineering, which is one of the modern high-tech medicines, and the basics of cell therapy are different. It is related to the production of microcapsules, which, as mentioned above, are currently undergoing preclinical animal experiments in xenografts using microcapsules. For this reason, standardized equipment related to the manufacture of microcapsules is on the market for the reason that there are very few study groups studying this topic. It is in a state of using different and unsightly experimental instruments. For this reason, cell therapies using microcapsules will be used directly in the treatment of patients in the near future, and in the meantime, there is a need for certain standardized and usable microcapsules. In the invention, a thickness of the solution tube 1 is maintained, and the solution tube 1 can be fixed at the center of the gas outlet 7 in the invention. The size of the microcapsules produced can be kept constant and evenly, thereby achieving standardization and standardization of the microcapsules produced.

Claims (5)

In the invention of the blower for producing microcapsules, Solution tube (1) through which the mixed solution of the microcapsule component and the cell suspension is passed, and the main body (3) through which the gas passes for blowing for spraying the mixed solution, and the solution tube outer outlet (5) at the center of the external gas outlet. Blower for manufacturing microcapsules, which consists of four parts: a holder (4) and a blower support (14) for manufacturing microcapsules located inside the main body (3) for fixation-positioning The fixing device according to claim 1, wherein the solution tube (1) is fixed near the main body converging portion (8) located in the lower part of the main body (3) through the main body (3) through which the gas passes. (4) The blower for manufacturing a microcapsule invented so that the solution pipe external outlet 5 is located at the central portion of the external gas outlet 7 through the central hole. The gas, which is harmless to the cells, used for spraying the mixed solution of the microcapsule component and the cell suspension, is injected through the gas inlet 2 of the body 3, and the injected gas is injected into the body 3. Blower for manufacturing a microcapsule for spraying the mixed solution while blowing through the outer outlet 7 of the gas (6) located in the lower center of the According to claim 1, while being fixed near the lower converging portion (8) inside the blower main body (3) for producing a microcapsule, the solution tube (1) passes through the small pores in the center, the solution outlet (1) outside the outlet ( Blower for manufacturing microcapsules with a fixing device (4) for fixing 5) to be located at the center of the gas outlet (7) The blower for manufacturing microcapsules according to claim 1, wherein the blower for producing microcapsules owning the support (9) is provided with a support (14) suspended from the main body (3).