KR20010091721A - Microporous and Biodegradable Artificial Organ with Controlled Released Bioactive Molecules and Its Manufacturing Methods - Google Patents

Abstract

PURPOSE: Provided is a method for producing multiporous and biodegradable artificial organs which release bioactive materials slowly, thereby transferring the material effectively through the artificial organs because the organs have the appropriate sized multiporous and releasing the bioactive materials slowly from the organs during growth of cells within organs. CONSTITUTION: The multiporous and biodegradable artificial organs are produced by adding 1.5 to 18% of biodegradable polymer and 0.0001 to 80% of bioactive materials selected from the group consisting of cytokines, antibiotics and the mixture thereof to emulsion solution consisting of water and organic solvent; adding the mixture into a mold with organ shape; and drying the artificial organs by emulsifying freeze drying method.

Description

Microporous and Biodegradable Artificial Organ with Controlled Released Bioactive Molecules and Its Manufacturing Methods}

The present invention relates to a porous and biodegradable artificial organs for sustaining the release of physiologically active substances and a method for preparing the same. More specifically, the porous and biodegradable polymers are required in a certain content ratio together with physiologically active substances such as cytokines and antibiotics. The porous body having a uniform diameter distribution prepared by emulsifying and freezing drying in a mold of a long-term form is embedded with the above-mentioned physiologically active substance so that it is sustained during cell growth as well as excellent prevention against various infections. Porous and biodegradable artificial organs that facilitate the attachment and growth of various specific tissue cells in the body, and after the growth of the cells is completed, release the bioactive substances that have the property of being naturally biodegraded and absorbed by the human body. It relates to a method for producing the same.

Despite the rapid growth of delicate, sophisticated and high-level medical engineering technology, diseases that damage human organs and tissues are accompanied by various accidents and advancement of health care levels, and with the aging of natural lifespan, enormous expenses for treatment. It is becoming more common throughout the society with relatively high frequency and serious problems.

When some organs or parts of the body are damaged by diseases or accidents, artificial organs are used to treat patients' diseases. The development history of these artificial organs, which have been around 100 years since Lane was used to fix bone fractures around 1890, can be divided into four generations.

The first generation was a very early transplant prior to 1940 that supported or prostheted some of the primitive metals and ceramics in the human body. These studies or procedures began with a basic curiosity rather than practicality or effects without much distinction between disciplines such as medicine, chemistry and materials.

The second generation begins with doctors replacing a part of a broken or damaged organ with a generic chemical material devised by researchers, accidentally and unexpectedly without an exact definition of abnormality, ie biocompatibility with tissues that come into contact with the human body. It was a time when it was applied. For example, Chanley uses polymethyl methacrylate bone cement as artificial hip joint, and Boris Lee uses nylon and polyacrylonitrile-based copolymer as artificial blood vessel in Korean war, plasticizing with diethylhexyl phthalate. This is an example of using vinyl chloride as a blood bag and using polyvinylpyrrolidone as an artificial blood during the Vietnam War. These examples have been widely used since the late 1950, when the operation was performed in earnest, with numerous clinical successes.

The third generation is the body and the "bioactive" state, i.e. very precisely designed and applied polymers, ceramics and metal materials, rather than the "inactive" state without any interaction with the living body highlighted in the first and second generations described above. Is a developmental generation of biomaterials that stimulate surrounding tissue cells to make transplantation faster and more effective. Typical examples include artificial hip joints coated with hydroxyapatite, artificial blood vessels coated with algin and collagen, and the like.

The fourth generation is the development of mixed artificial organs using tissue engineering, that is, tissue cells extracted from the human body and synthetic materials are used simultaneously. They focus on improving and restoring damaged tissues, rather than completely replacing organs of the human body with reoperations. The fundamental reason for the development of artificial organs with the fourth generation of tissue engineering is that the general limitations of general synthetic polymers, namely, biocompatibility and the biofunctionality of damaged organs or tissues of a certain part, are eventually lacked. . Accordingly, the company is pursuing a hybrid that mimics biological elements by binding, immobilizing, and cultivating cells or proteins, which are responsible for specific functions of organs, to non-degradable polymer materials to further enhance and functionalize desired tissues or organs. .

As a representative example of such a histological study, the artificial cartilage is schematically described as follows. First, a specific organ shape in the human body is sculpted with gypsum and the like, and then a long-term mold is manufactured using copper plate and silicon. A carrier to be supported and grown by chondrocytes in the mold of the organ form must be prepared. As such a carrier, microporous and biodegradable polymers are usually used. Recently, as biopolymers of synthetic polymers, ester copolymers of lactide and glycolide are used, and their biodegradation mechanism is due to hydrolysis.

Polylactide (PLA) is used to manufacture bone fixation plates and screws to fix broken bones, and polyglycolide (PGA) is widely used as an absorbent suture. Although the biodegradation period of these homopolymers is somewhat different depending on the molecular weight, it is usually 1 year or more, whereas their copolymer, polyglycolide-lactide (PLGA), undergoes biodegradation over several weeks to several tens of weeks depending on the molecular weight.

As a method for producing a microporous and biodegradable carrier (for example, a sponge-like structure) using a PLGA biodegradable polymer, it is mixed with a monocrystalline salt of a certain size in a solution in which PLGA is dissolved, and the salt is dried in water. Salt extraction method to dissolve, expansion of PLGA using carbon dioxide, production of PGA mesh from nonwoven fabric of PGA fiber, evaporation of solvent in PLGA solution, solvent in PLGA solution Phase separation methods, such as immersion in phases, are applied. Then, cartilage cells isolated and mass cultured from rabbit ears are harvested through a series of operations and seeded in ear and nose biodegradable carriers. And, when transplanted into the laboratory animals, the biodegradable polymer is naturally absorbed into the animal body, and finally only cartilage is left to replace the role of the lost organs. At this time, hepatocytes, small intestine cells, urinary tract cells, vascular endothelial cells, bone marrow cells, nerve cells, etc. are applied as tissue cells to be separated and seeded, and thus, space, artificial field, artificial urinary tract, artificial blood vessel, artificial bone marrow, artificial It can be applied to nerves and other organs.

On the other hand, the present inventors have proposed a porous and biodegradable artificial organs and a method for producing the same by the emulsion freeze drying method consisting of a polymer solution and water to solve the other disadvantages (Korea Patent No. 201,874). However, the preparation method according to Korean Patent No. 201,874 has a disadvantage in that the surface properties of the synthetic biodegradable polymer used are hydrophobic so that the culture medium and the cells do not penetrate into the biodegradable polymer carrier and do not grow. In addition, when the biodegradable polymer carrier contains cytokines of various growth factors, various properties such as angiogenesis and neuronal cell formation can be remarkably increased, but bioactive substances are denatured and water is produced during the manufacturing process. And other solvents pre-flowed out and lost their original function.

Accordingly, the present inventors have tried to solve the problems found in the above-mentioned Korean Patent No. 201,874, and to develop an improved artificial organ. As a result, the biodegradable polymer material that is implanted into the human body and biodegradable for a certain period of time is selected and used, and the long-term mold is filled with an emulsion solution in which various bioactive substances are mixed in an incompatible liquid with the selected biodegradable polymer solution. The present invention was completed by preparing a porous and biodegradable artificial organ using a so-called emulsification freeze drying method of drying after freezing.

That is, in the present invention, even though the surface property of the selected biodegradable polymer is hydrophobic, the hydrophilic physiologically active substance is entrapped, so that the culture medium and the cells are easily permeated, and the cell growth is rapid, and the manufacturing process is lyophilized. Because of the simple operation, it was possible to solve the problem of degeneration of bioactive substances or the flow of water and other solvents during the manufacturing process, and the inclusion of bioactive substances decomposed into biodegradable polymers at the same time. Since the cells are sustained during the cell growth process, the cell growth rate can be kept constant.

Accordingly, an object of the present invention is to provide an artificial organ and a method for producing the same which are excellent in bioactivity and other functionalities and naturally biodegraded and absorbed by the human body after a certain period of time.

1 is an electron micrograph (× 200) of a porous biodegradable artificial organ containing a nerve growth factor (NGF) produced by the manufacturing method according to the present invention.

2 is an elution graph of nerve growth factor (NGF) over time,

3 is a photograph showing the results of the wetting test for the porous, biodegradable artificial organs containing gentamicin sulfate prepared by the manufacturing method according to the present invention,

4 is an elution graph of antibiotics (gentamicin sulfate) over time.

The present invention is a method for producing a porous and biodegradable artificial organs for sustained release of a bioactive material to emulsify and freeze-dried by injecting a mixed solution of a bioactive material and a biodegradable polymer into an emulsion of water and an organic solvent. It is characterized by.

In addition, the present invention includes a porous, biodegradable artificial organs for sustained release of the physiologically active substance prepared by the above-described manufacturing method, such artificial organs include artificial blood vessels, artificial cartilage, artificial bones, human space, such as tissues Any of these recoverable body organs can be applied.

The present invention will be described in more detail as follows.

The present invention relates to an artificial organ and a method for producing the sustained release of a bioactive material produced by emulsification freeze drying of a biodegradable polymer material. The artificial organ according to the present invention is composed of a sponge-type biodegradable polymer having a pore size distribution and implanted in the human body so that culture medium and cells can easily penetrate into the biodegradable carrier, thereby allowing the growth and recovery of tissue cells. In addition, artificial organs are slowly biodegraded by hydrolysis after a certain period of time, and are not absorbed by the human body and accumulated in the human body, and bioactive substances contained in the artificial organs are denatured or water and other solvents are There is no fear of bleeding out, and the bioactive substance is given a function of slowly releasing, ie, sustained release for a desired period, and has excellent excellence in maintaining a constant cell growth rate.

Hereinafter, the manufacturing process of the artificial organ according to the present invention will be described in detail.

The biodegradable polymer used in the present invention should be harmless to the human body and have properties that can be biodegraded within a desired period of time. Biodegradable polymers having such characteristics include albumin, collagen, gelatin, fibrinogen, casein, fibrin, hemoglobin, and transferrin. (transferrin), chitin, chitosan, hyaluronic acid, heparin, chondroitin, keratin sulfate, alginic acid, starch, dextrin, Dextran, citric acid, polylactic acid, polyglycolic acid, lactic acid-glycolic acid copolymer, polyhydroxybutyric acid, polycaprolactone, polyanhydride and polyalkylcyano acrylate At least one selected from polyalkylcyano acrylate is used. These biodegradable polymers have been found to naturally biodegrade after a certain period of time in the human body by hydrolysis and various enzymes in the human body [Langer. R & Vacanti JP, Science 260 , 920, 1993].

In addition, the present invention uses cytokines, antibiotics, or mixtures thereof, which are bioactive substances, for the purpose of imparting various renal functions such as growth of human tissue cells, growth of blood vessels, and prevention of infection.

Cytokines used in the present invention as physiologically active substances include growth factors, bone morphogenic proteins, interleukins 1-17, interferons, and the like. Growth factors include platelet derived growth factor (PDGF), transforming growth factor (TGF), epidermal growth factor (EGF), insulin-like growth factor, IGF), acidic and basic fibroblast growth factor (aFGF, bFGF), vascular endothelial growth factor (VEGF), nerve growth factor (NGF), 6 CKINE, fluid Activin A, amphiregulin, angiogenin, betacellulin, brain-derived neurotropic factor (BNDF), ciliary neurotrophin factor , CNTF), cytokine-induced neutrophil chemoattractant-1, β-endothelial cell growth factor β-ECGF, epithelial cell activator-78 neutrophil activating peptide-78, ENA-78), heparin attached epidermal growth factor (heparin) -binding epidermal growth factor-like growth factor (HB-EGF), fibroblast growth factor 4-9 (FGF 4-9), glia cell line-devived neutrotrophic factor, GDNF), GLY-HIS-LYS, granulocyte colony stimulating factor (G-CSF), hepaocyte growth factor (HGF), keratinocyte growth factor (KGF), Neutrotropin (neutrotrophin, NT), placenta growth factor (PIN), stem cell factor (stem cell factor (SCF), tumor necrosis factor (TNF) is selected from one or more. Said cytokines have been found to provide activity, such as growth, adhesion, migration, etc. of human specific cells, tissues and organs.

The antibiotic used in the present invention as another bioactive substance is a water-soluble antibiotic, beta-lactam, aminoglycoside, penicillin, gentamycin, canayacin, ampicillin, polymyxin-B (polymyxin-B). B), amphotericin-B (amphotericin-B), aztreonam, cephalospo-rins, chloroamphenicol, fusidans, lincosamides ), Macrolides, metronidazole, nitro-furantoin, impenem / cilastin, quinolones, rifampin, polyenes 1 selected from tetracycline, sulfonamides, trimethoprim, vancomycin, teicoplanin, imidazoles and erythro-mycin More than a species.

In the production method according to the present invention, it is preferable to contain cytokines as an essential ingredient as the physiologically active substance and to use antibiotics as necessary.

In addition, in order to perform the emulsifying freeze drying method (Emulsifying Freeze Drying Method) which is the main point of the present invention, a mold of an organ form of a specific body part is required. The mold is made of materials such as teflon, polyethylene, ultra high molecular weight polyethylene, and various changes are possible depending on the shape of the artificial organ. It should be noted, however, that no emulsified biodegradable polymer should be attached. For example, when the material of the mold is made of stainless steel, copper, aluminum, polymethyl acrylate, polycarbonate, etc., the biodegradable polymer in the porous form is strongly adhered due to the property of attaching to the biodegradable polymer and is easily separated from the mold. Does not become.

Complete emulsion solution using ultrasonic or homogenizer in a mixed solution containing 1.5 to 18% of biodegradable polymer and 0.0001 to 80% of biodegradable polymer in an emulsion solution composed of 10 to 70% by weight of water and 30 to 90% by weight of organic solvent. Make it. The complete emulsified solution is immediately put into a mold of a certain type and lyophilized to prepare a porous and biodegradable artificial organ.

In dissolving the biodegradable polymer in an emulsion solution having the composition described above, the biodegradable polymer is dissolved in an emulsion solution in which an organic solvent and water in which a bioactive substance is dissolved are mixed or dissolved in an organic solvent. Water in which the bioactive material is dissolved may be added, or after dissolving in water in which the bioactive material is dissolved, an organic solvent may be added. The method of dissolving the biodegradable polymer or the selection of the organic solvent can be varied by conventional methods well known in the art depending on the characteristics and circumstances. For example, in the case of lactic acid-glycolic acid copolymer, it is particularly preferable to use one selected from acetonitrile, dichloromethane, chloroform, tetrahydrofuran, dioxane and methylene chloride as an organic solvent. The biodegradable polymer is dissolved in the concentration of 0.003-27% in the emulsion, and more preferably in the concentration of 1.5-18%. If the concentration is less than 1.5%, the biodegradable polymer concentration is too low, so the porous tissue state is too weak. If the concentration exceeds 18%, the porous tissue state is too dense, which may hinder the growth of tissue cells. to be. The emulsion solution containing the biodegradable polymer is completely prepared as an emulsion solution by ultrasonic or homogenizer. When water is added to the emulsification solution, a solution obtained by dissolving the physiologically active substance in the water phase in a concentration of 0.0001 to 80% (W / V) according to the characteristics of each selected compound is used. At this time, the pore size, pore size distribution, porosity, etc. can be variously changed according to the type of artificial organ to be prepared, which is possible by controlling the composition ratio of the biodegradable polymer organic solvent and water used.

The emulsified solution containing the biodegradable polymer and physiologically active material thus prepared is quickly poured into a mold, and then frozen in liquid nitrogen to a temperature of less than 0.5 to 1 hour and lower than −35 ° C., followed by drying with a lyophilizer. Finally, when the dried porous body is separated from the mold, a porous, biodegradable artificial organ which sustains the physiologically active substance of the present invention is obtained.

In addition, the artificial organs produced in the present invention are applicable to any organs capable of growth and recovery of tissue cells such as artificial blood vessels, artificial urethra, artificial small intestine, artificial bronchus, human space, artificial kidney, artificial cartilage, and the like.

Since the porous and biodegradable artificial organs prepared as described above use each type of mold forming the human organs, the desired shape can be freely obtained, and the pore size, pore size distribution, and porosity include biodegradable polymers. There is an advantage that can be properly adjusted by adjusting the ratio of the solution and water to. In addition, since the biodegradation period of the porous biodegradable artificial organ implanted in the human body may be longer as the molecular weight of the biodegradable polymer used and the fraction of any one of lactide and glycolide are higher. Arbitrarily adjustable. In addition, the so-called sustained-release period in which each bioactive substance flows out can be adjusted according to the amount of drug applied according to the pharmacological duration of each bioactive substance and antibiotic.

Hereinafter, the present invention will be described in detail with reference to the following Examples, the present invention is not limited by the Examples.

Example 1

Lactic acid and glycolic acid (glycolic acid) is mixed at a ratio of 75: 25% by weight, and then copolymerized by thermal polymerization at 170 ° C and 100 rpm for 4 hours in the presence of a stenoose octoate catalyst (150 ppm). Was prepared. The molecular weight of the prepared copolymer (hereinafter referred to as "PLGA 75") was analyzed by gel permeation chromatography (Gel Permeation Chromatography) was 110 kg / mol.

0.8 g of the prepared PLGA 75 was evenly dissolved in 8 ml of methylene chloride, and the solution was mixed with water in which 1 µg and 500 ng of NGF were dissolved at a ratio of 60:40, followed by 40 W strength. Emulsion solution was prepared for 30 seconds using an ultrasonic mixer. The emulsion solution was quickly poured into a teflon tubular mold having an outer diameter of 8 mm and an inner diameter of 4 mm, immersed in liquid nitrogen at -196 ° C, and frozen immediately. After leaving for one day in this, it was dried using a freeze dryer under a pressure of -78 ℃, 0.1 torr.

Electron micrographs (× 200) of porous and biodegradable artificial organs containing nerve growth factor (NGF) prepared by the above method are shown in FIG. 1.

In addition, in order to measure physical properties such as pore size, pore size distribution and total pore area, mercury porosimeters (Porosimeter, AutoPoreII, Microme-ritrics) were measured, and NGF detected by ELISA was sustained. The graph is shown in FIG.

Example 2

PLGA 75 was polymerized in the same manner as in Example 1, where 30 ppm of stenosoctoate catalyst was added. The molecular weight of the GPC was 370 kg / mol. 0.8 g of the PLGA 75 was evenly dissolved in methylene chloride, and the solution was mixed with water in which the gentamicin sulfate was dissolved at concentrations of 0.4, 0.8 and 6 mg / ml at a ratio of 70:30, and then using an ultrasonic mixer. To prepare an emulsion solution. It was carried out in the same manner as in Example 1 below. As a result, their physical properties are shown in Table 1 below.

In addition, in order to determine the synergistic effect, the solution was penetrated into the blue dye dissolved solution 6 hours after the phenomenon was observed, the photo is shown in FIG. In addition, the release graph of gentamicin cellulose detected from the PLGA carrier by HPLC is shown in FIG. 4.

Example 3

0.8 g of polyhydroxybutyric acid (PHB) having a molecular weight of 15 kg / mol was dissolved in 8 ml of chloroform, and the solution was mixed with 0.03% of TGF-dissolved water at a ratio of 50:50 and then used with an ultrasonic mixer. To prepare an emulsion solution. It was carried out in the same manner as in Example 1 below. As a result, their physical properties are shown in Table 1 below.

Example 4

After dissolving 1.2 g of polycaprolacto (PCL) having a molecular weight of 37 kg / mol in 8 ml of dioxane, the solution was mixed with distilled water containing 0.002% brain extract neuronal factor in a ratio of 40:60. , Using an ultrasonic mixer to prepare an emulsion solution. It was carried out in the same manner as in Example 1 below. As a result, their physical properties are shown in Table 1 below.

Example 5

1 g of low viscosity alginic acid and 0.02 g of tetracycline are dissolved in 10 ml of distilled water, and the solution is mixed with dichloromethane at a ratio of 50:50, and then an emulsion solution is prepared using an ultrasonic mixer. It was. It was carried out in the same manner as in Example 1 below. As a result, their physical properties are shown in Table 1 below.

Example 6

An aqueous solution containing 6% glucose, 70% textan, 500 ng stem cell factor and 0.06% citric acid was mixed with acetonitrile at a ratio of 90:10, and an emulsion solution was prepared using an ultrasonic mixer. It was carried out in the same manner as in Example 1 below. As a result, their physical properties are shown in Table 1 below.

Comparative example

A tubular porous artificial organ was prepared in the same manner as in Example 1, except that the biodegradable polymer organic solution and water were mixed in a weight ratio of 10:90.

According to the above results, the porous / biodegradable artificial organ according to the present invention has an average pore size of about 15 μm, but if the ratio of water in the emulsion solution is excessive, as in the comparative example, the artificial organ is not manufactured. This is because it is below the critical concentration at which the void must be made. In addition, depending on the concentration of NGF, gentamicin sulfate and other physiological activators, the desired amount of sustained release of bioactive substances and antibiotics can be achieved within a desired period. It can be seen that it can be quickly penetrated to increase the hydrophilization of the carrier by the present method to achieve the object of the present invention excellently.

As described above, the artificial organ produced by the manufacturing method according to the present invention has an appropriate pore size, so that the material transfer such as nutrient solution, oxygen, carbon dioxide, etc. between the blood and the skin is effective, and the connection between the pores is biodegradable Because it is made of polymer, it is easy to attach and grow vascular endothelial cells or skin tissue cells in the human body, and after the growth of these cells is completed, they are naturally biodegradable and absorbed by the body. Have.

In addition, cytokines and antibiotics as added bioactive substances can functionalize biodegradable polymer carriers, which are indispensable in the development of conventional tissue engineering organs in that they can be sustained as desired as biodegradable polymers are decomposed. It has the advantage of being much easier and more economical than conventional methods.

Claims (9)

The emulsification solution of water and organic solvent is emulsified by adding a mixed solution containing 1.5-18% of biodegradable polymer and 0.0001-80% of bioactive substances selected from cytokines, antibiotics and mixtures thereof into a mold. A method for producing a porous, biodegradable artificial organ that sustains releasing physiologically active substances, characterized by lyophilization. According to claim 1, wherein the biodegradable polymer is polylactic acid, polyglycolic acid, lactic acid-glycolic acid copolymer, albumin, collagen, gelatin, fibrinogen, casein, fibrin, hemoglobin, transferrin, chitin, chitosan, high At least one selected from aruronic acid, heparin, chondroitin, keratin sulfate, alginic acid, starch, destrin, dextran, citric acid, polyhydroxybutyric acid, polycaprolactone, polyanhydride and polyalkylcyanoacrylate A method for producing a porous, biodegradable artificial organ that sustains releasing a physiologically active substance. The method of claim 1, wherein the emulsion solution comprises 30 to 90% by weight of an organic solvent and 10 to 70% by weight of water. The method of claim 1 or 3, wherein the organic solvent is at least one selected from acetonitrile, dichloromethane, chloroform, tetrahydrofuran, dioxane and methylene chloride, porous and biodegradable to sustain the bioactive substance Method of manufacturing sex artificial organs. The method of claim 1, wherein the emulsification freeze drying is a process of freezing and drying at −35 ° C. or lower. The method of claim 1, wherein the mold is one or more materials selected from Teflon, polyethylene, and ultrahigh molecular weight polyethylene. The method of claim 1, wherein the cytokines are platelet derived growth factor (PDGF), transforming growth factor (TGF), epidermal growth factor (EGF), insulin growth factor (insulin-like growth factor, IGF), acidic and basic fibroblast growth factor (aFGF, bFGF), vascular endothelial growth factor (VEGF), nerve growth factor (nerve growth factor, NGF), 6 CKINE, activin A, amphiregulin, angiogenin, betacellul-in, brain-derived neurotropic factor, BNDF ), Ciliary neurotrophin factor (CNTF), cytokine-induced neutrophil chemoattractant-1, and β-endothelial cell growth factor (β-ECGF) , Epithelial cell activator-78 (epithelial neutrophil activating peptide-78, ENA-78), heparin Heparin-binding epidermal growth factor-like growth factor (HB-EGF), fibroblast growth factor 4-9 (FGF 4-9), glioblastoma cell growth factor (glial cell) line-devived neutrotrophic factor (GDNF), GLY-HIS-LYS, granulocyte colony stimulating factor (G-CSF), hepaocyte growth factor (HGF), keratinocyte growth factor (keratinocy-te growth) factor, KGF), neutrotrophin (NT), placenta growth fact-or (PIGF), stem cell factor (SCF), tumor necrosis factor (TNF) Method for producing a porous, biodegradable artificial organs for sustained release of the bioactive material, characterized in that at least one selected. The method of claim 1, wherein the antibiotic is beta-lactam, aminoglycoside, penicillin, gentamycin, kanayacin, ampicillin, polymyxin-B (polymyxin-B), amphotericin-B (amphotericin-B), aztreonam, cephalospo-rins, chloroamphenicol, fusidans, lincosamides, macrolides, Metronidazole, nitro-furantoin, impenem / cilastin, quinolones, rifampin, polyenes, tetracycline, snow Biological activity characterized in that at least one selected from sulfonamides, trimethoprim, tricomopin (vancomycin), teicoplanin (teicoplanin), imidazole (imidazol-es) and erythromycin (erythromycin) Method for producing porous, biodegradable artificial organs that sustain the release of substances. A porous, biodegradable artificial organ which sustains physiologically active substances, which is prepared by the method of claim 1.