KR101775079B1 - Catheter cotaining organic germanium and method for preparing the same - Google Patents
Catheter cotaining organic germanium and method for preparing the same Download PDFInfo
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Abstract
TECHNICAL FIELD The present invention relates to a catheter containing organic germanium and a method for producing the catheter, and more particularly, to a catheter having organic germanium incorporated in a polymer and coating the surface of the polymer with organic germanium and a method for producing the catheter. The catheter according to the present invention is a catheter in which organic germanium is incorporated into a polymer and the surface of the polymer is coated with organic germanium. The catheter is excellent in antioxidative and anti-cell suicide functions, and can suppress oxidative stress of cells or living tissues And the treatment efficiency is increased.
Description
The present invention relates to a catheter containing organic germanium and a method for producing the same, and more particularly, to an antioxidative catheter prepared by compounding organic germanium in a polymer and coating the surface of the polymer with organic germanium and a method for producing the catheter .
Germanium is a semiconducting substance that combines hydrogen molecules and oxygen molecules generated in a metabolic process in which nutrients are burned in vivo, and dehydrogenation, which releases water to the outside of the body through the urine or sweat, along with other waste materials. . Germanium is a typical semiconducting material having metallic and sub-metallic properties. It is contained in a sub-metallic mineral and vegetation in the ground layer and is excellent in far-infrared radiation performance and applied to various application fields. Particularly, in the past, the germanium component has been applied to the field of electronic engineering using the semiconductor property possessed by the germanium component. However, since the biochemical effect of the germanium component is known, the application range has been extended to the field of fertilizer, feed and food. Specifically, germanium has been attached to the composition compound for the purpose of removing impurities by supplying oxygen to the skin tissue, and for the purpose of cleansing the skin and antimicrobial function, preventing aging due to far infrared rays emission, reducing wrinkles, acne, pore contraction, keratin and waste materials, It has the advantage of wide range of applications because there is no toxin component in human skin tissue. Since germanium has inorganic germanium and organic germanium, inorganic germanium causes adverse effects on the human body. In 1967, toxic and physiological germanium carboxyethyl germanium sesquioxide (Ge-132) was developed. As the organic germanium effect, early erythropoiesis promoting action and antimicrobial action have been reported, and recently, studies on anticancer effect and immune formation promoting effect have been reported.
A catheter is a thin tube made by extrusion molding using medical materials. It is a medical instrument that is inserted into a human body when dealing with a bottle in the medical field or when performing surgery. It is used for various purposes such as vascularization, insertion of the urethra, insertion of the airway, It is used for the purpose. In addition, in the development of modern medicine, cell therapy catheters capable of delivering cells are being developed in advanced countries such as the United States and Europe in cell therapy through cell transplantation. However, as the catheter is directly inserted into the body during the procedure, there is a problem that the body is infected by the catheter. Oxidative stress of cells and tissues during insertion of the catheter induces weakening of the immune resistance of the cells and inflammation, and then gradually leads to cell aggregation and adhesion between the tissue and the insertion catheter. This problem is a major cause of deteriorating the efficiency of therapeutic target cell transplantation. In addition, the incidence of central venous catheter-related bloodstream infections increases with the long-term in vivo transplantation of the catheter, and more than 1,000 cases occur in Korea every year. In case of intracerebral infection in ICU, the mortality rate is 35% , An average hospital stay of 32 days is reported to increase.
Therefore, development of a catheter having an antioxidant and anti-cell suicide function capable of alleviating the oxidative stress to which cells and living tissues at the catheter insertion site are applied and protecting the cells transplanted for therapeutic purposes through a catheter to improve the transplantation efficiency Is desperately required.
The inventors of the present invention have found that a catheter having organic germanium incorporated into a polymer and coated with organic germanium on the surface of the polymer is excellent in antioxidant and anti-cell suicide functions, And the treatment efficiency is increased by reducing the oxidative stress of the tissue. Thus, the present invention has been completed.
Thus, the present invention relates to a polymer comprising organic germanium incorporated therein; And organic germanium coated on the surface of the polymer. ≪ Desc /
The present invention also provides a catheter kit comprising the catheter.
The present invention also provides a culture medium composition for in vitro fertilization comprising organogermanium.
In order to achieve the above object,
The present invention relates to a polymer blended with organogermanium; And organic germanium coated on the surface of the polymer.
The present invention also relates to a process for the production of organic germanium, comprising combining organic germanium with a polymer; And coating organic germanium on the surface of the polymer.
The present invention also provides a catheter kit comprising the catheter.
The present invention also provides a medium composition for in vitro fertilization comprising organogermanium.
Hereinafter, the present invention will be described in detail.
The present invention
A polymer in which organic germanium is blended; And organic germanium coated on the surface of the polymer.
The present invention relates to a catheter having an antioxidant and anti-cell suicide function, and relates to a catheter in which organic germanium is blended with a polymer as a catheter material and organic germanium is coated on the surface of the polymer.
The organic germanium is carboxyethyl germanium sesquioxide (trade name: Ge-132), which is germanium harmless to humans, which is synthesized as a compound of germanium contained in natural plants such as mushrooms and garlic.
The organic germanium may be blended with a polymer as a catheter material and coated on the surface of the polymer, and may be 0.01 to 20 wt%, preferably 0.01 to 5 wt%, based on the total weight of the polymer. The incorporation of organic germanium into the polymer matrix can be carried out in any conventional mixing equipment in which the polymer is melted and mixed with organic germanium. Suitable equipment is known to the person skilled in the art and can principally be a mixer, kneader and extruder. The compounding of the organic germanium is carried out by known methods such as dry blending in powder form or wet blending in the form of, for example, a solution, dispersion or suspension in an inert solvent, water or oil. The organogermanium of the present invention may be formulated, for example, before or after shaping, or may be formulated by applying dissolved or dispersed organogermanium to the polymer material. This may be added directly to the processing equipment (e.g., extruder, internal mixer, etc.), for example as a dry mixture or powder, or as a solution or dispersion or suspension.
The polymer may be one that is commonly used in the medical field and may be any form of fiber, film, or molded article. Specifically, the polymer may be a polyurethane, a polycarbonate, a silicone, a polyethylene, a polypropylene, a polyimide, a polyester, a polysulfone, a polyvinyl chloride, a latex, a polyvinyl alcohol, .
An antioxidant, an antibacterial agent, an anti-inflammatory agent or a combination thereof may be further added to the polymer. In recent years, there have been many cases of infectious diseases due to sterilization or misuse of catheters. Especially, when the catheter is inserted into the intestines, urethra, or organs, urine may flow back from the inside of the catheter, . In addition, a balloon catheter is a catheter used for cardiac surgery, and if a single germ penetrates, it can lead to a medical accident and kill the patient's life. The catheter of the present invention relates to a catheter capable of imparting not only antioxidative and anti-cell suicidal effects but also antibacterial and anti-inflammatory effects.
The antioxidant is a substance for inhibiting active oxygen, which can be blended into the polymer during the manufacturing process of the catheter and coated on the outer surface of the polymer. Specifically, the antioxidant may be selected from the group consisting of resveratrol, nordihydroguaiarectic acid, viniferin, quercetin, fisetin polyphenol, butaine butein, piceattonol, isoliquiritigenin, vitamin, tocopherol, and the like, preferably resveratrol.
The antimicrobial agent may be any antimicrobial active group and may be selected from the group consisting of phenylcylin, cephalosporin, aminoglycoside, chloramphenic, tetracycline, macrolide, An inorganic antibacterial agent composed of copper, tin, silver, chromium, titanium dioxide, zeolite and the like can be used. Specifically, it is an oleophilic element of beta-lactam, chloramphenicol, rinkosamide, macrolide, penicillin, quinolone, sulfonamide, tetracycline, and lipophilic antimicrobial agent is preferably benzathine, phenoxymethylpenicillin, chloramphenicol, Erythromycin < RTI ID = 0.0 > glutamate, erythromycin < / RTI > glutamate, erythromycin glutamate, erythromycin glutamate, erythromycin < RTI ID = 0.0 > glutamate, Erythromycin stearate, erythromycin stearate, fusidic acid, and preferably free lipophilic elements such as free fusidic acid, gramicidin, nonpyrosine, imidazole, e. G. Azathioprine, itraconazole, clotrimazole Sol, pristinamycin, rifabutin, riapapentin, rifampicin, silver sulfadiazine, and the like.
The anti-inflammatory agent may be selected from the group consisting of glycyrrhizic acid, glycyrrhetic acid, allantoin, azulene, mefenamic acid, phenylbutazone, indomethacin, Ibuprofen, ketoprofen, epsilon-aminocaproic acid, hydrocortisone, panthenol, zinc oxide, diclofenac sodium, and the like. ), Aloe extract, beefsteak plant extract, mugwort extract, camomile extract, comfrey extract, sanguisorba root extract, water-cress extract, and the like.
The antioxidant, the antimicrobial agent, the anti-inflammatory agent, or a combination thereof may be 0.01 to 20% by weight, preferably 0.01 to 5% by weight, based on the total weight of the polymer, but is not limited thereto.
The catheter is used for medical purposes and refers to all means directly inserted into the body. It is used for various purposes such as blood vessel insertion, urethra insertion, airway insertion, laparoscopic surgery, and the like. As these catheters are inserted directly into the body during the procedure, it is important to prevent body infection by the catheter. Catheters are also called catheters, and they have various shapes and thicknesses, and they vary in type and purpose.
The catheter is characterized by having an antioxidant and anti-cell suicide function by containing organic germanium, especially Ge-132. According to one embodiment, the organic germanium contained in the catheter promotes the expression of the Nrf-2 gene, an antioxidant-related gene, and inhibits the expression of the Bax gene, an anti-cell suicide-related gene.
The purpose of the catheter is to alleviate the oxidative stress to which the cells injected for therapeutic purposes and the cells at the site where the catheter is inserted. The catheter may be a cell-free or extracorporeal cell, and the cell may be a stem cell, a pluripotent cell, a functional cell, or the like.
The catheter may be a urethral drainage catheter, a balloon catheter, a Hikman catheter, an organ catheter, a dental decantation catheter, a liposuction catheter, a cervical catheter, etc. In addition, a catheter used for otolaryngology or surgery may be provided with an antioxidant and anti- Catheter.
The present invention also relates to a process for the production of organic germanium, comprising combining organic germanium with a polymer; And coating organic germanium on the surface of the polymer.
The present invention also provides a catheter kit comprising the catheter.
The present invention also provides a medium composition for in vitro fertilization comprising organogermanium.
The medium composition may increase nuclear or cytoplasmic maturation, embryonic development, sperm penetration, antioxidant, anti-cell suicide function. According to one embodiment, the organic germanium may be contained in the culture medium at a concentration of 1 to 500 占 퐂 / mL, preferably at a concentration of 100 to 200 占 퐂 / mL, and the culture medium containing the organic germanium may contain Or glutathione (GSH) and reduce reactive oxygen species (ROS) in cytoplasmic maturation, increase the number of cells in the blastocyst after embryo development after in vitro fertilization, and increase gene expression in oocyte or cumulus cells Is increased.
The catheter of the present invention is excellent in antioxidant and anti-cell suicide function, and also has an advantage of reducing the oxidative stress of cells or living tissues generated during catheter insertion, thereby increasing the therapeutic efficiency.
The catheter according to the present invention is a catheter in which organic germanium is incorporated into a polymer and the surface of the polymer is coated with organic germanium. The catheter is excellent in antioxidative and anti-cell suicide functions, and can suppress oxidative stress of cells or living tissues And the treatment efficiency is increased.
Figure 1 shows (a) Epifluorescent microscopic images of in vitro maturation porcine oocytes and (b) levels of intracellular GSH and ROS. (D, h): 400 占 퐂 / ml, and the cells (b, f) To detect the levels of GSH and ROS, (ad) was stained with CellTracker blue and (eh) was stained with 2 ', 7'-dichlorodihydrofluorescein diacetate.
FIG. 2 is a graph showing the percentage of virgin reproductive-activated embryos developed in (a) 2-day reproductive-activated (PA) embryos and (b) 7-day blastocyst stage. Here, Ear BL (early blastocyst), Exp BL (expanded blastocyst), and Hat BL (hatched blastocyst).
FIG. 3 is a graph showing (a) the inconvenience rate of a 2-day IVF embryo and (b) the percentage of in vitro fertilized embryos developed at the 7th blastocyst stage. Here, Ear BL (early blastocyst), Exp BL (expanded blastocyst), and Hat BL (hatched blastocyst).
FIG. 4 is a graph showing mRNA gene expression levels for GAPDH (control group) of PCNA , POU5F1 , Nrf-2 , Bax , Bcl-2 and Caspase-3 in (a) oocytes and (b) cumulus cells.
Hereinafter, preferred embodiments of the present invention will be described in order to facilitate understanding of the present invention. However, the following examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited by the examples.
Example 1. Preparation of a catheter containing organic germanium
First, carboxyethyl germanium sesquioxide (trade name: Ge-132) was purchased from Sigma-Aldrich, and 0.1% by weight of organic germanium was added to the total weight of the polyurethane to prepare a blend. Thereafter, the formulation was extruded in an extruder into a tubular shape and cooled to prepare a catheter body. Organic germanium was coated on the surface of the catheter body by immersing the catheter body in an organic germanium solution and drying it in a dryer for 1 hour.
Experimental Example 1. Effect of organic germanium on nuclear and cytoplasmic maturation during in vitro maturation
The effects of organic germanium on nuclear and cytoplasmic maturation during in vitro maturation (IVM) of pigs were evaluated in the mid-stage II (MII) stage. First, the influence of organic germanium on the nuclear maturation ability is shown in Table 1.
(쨉 g / mL)
As shown in Table 1, there was no significant difference in nuclear maturation performance between the control (G-132 untreated group) and Ge-132 treated group in the middle stage II (MII) stage.
In order to evaluate cytoplasmic maturation, the levels of intracellular glutathione (GSH) and reactive oxygen species (ROS) in medium II (MII) oocytes derived from organic germanium-supplemented maturation medium after porcine in vitro maturation Respectively.
Epifluorescent microscopic images of in vitro matured porcine oocytes are shown in Figure 1 (a), and levels of intracellular GSH and ROS are shown in Figure 1 (b). (D, h): 400 占 퐂 / ml, and the cells (b, f) To detect the levels of GSH and ROS, (ad) was stained with CellTracker blue and (eh) was stained with 2 ', 7'-dichlorodihydrofluorescein diacetate.
As shown in FIG. 1, the germanium treated group showed a tendency to increase in the intracellular GSH compared with the control group, and the most increase was observed especially in the group treated with 200 g / mL organic germanium. In addition, ROS tended to decrease with increasing concentration of organic germanium (P <0.05).
Experimental Example 2. Influence of organic germanium supplemented to maturation medium on subsequent embryo development after virgin reproduction and in vitro fertilization
After porcine virgin reproductive activation (PA) and in vitro fertilization (IVF), the effects of organic germanium supplemented to maturation medium on subsequent embryonic development were evaluated. First, the effects of organic germanium supplemented to the maturation medium on embryonic development in the virgin reproductive activated embryo are shown in Table 2.
(쨉 g / mL)
(Number of blastocysts examined)
(Percent of matured oocytes,%)
(Percent of matured oocytes,%)
As shown in Table 2, the breakthrough of the virgin reproductive-activated (PA) embryo was found to increase gradually as the organic germanium concentration increased. Thus, the virgin reproductive activated embryo from the 400 ㎍ / mL organismic germanium treated group showed the highest cleavage rate (82.7%). However, the embryo developmental ability to the blastocyst stage and total cell number in blastocysts was significantly higher in the 200 ㎍ / mL organic germanium treated group than in the control group.
In order to evaluate the effect of supplemented organic germanium on the mature medium, the incomplete rate of the 2nd day reproductive activated (PA) embryo is shown in Fig. 2 (a), and the percentage of the virgin reproductive activated embryo developed at the 7th blastocyst stage 2 (b). Here, Ear BL (early blastocyst), Exp BL (expanded blastocyst), and Hat BL (hatched blastocyst).
As shown in FIG. 2 (a), in the group treated with 400 g / ml organic germanium compared with 100 g / ml germanium treated group on
Table 3 also shows the effect of organic germanium supplemented to the maturation medium on embryonic development after IVF.
(쨉 g / mL)
(Number of blastocysts examined)
(Percent of matured oocytes,%)
(Percent of matured oocytes,%)
As shown in Table 3, in vitro fertilization (IVF) embryos showed the highest incarceration rate (73.1%) in the 200 g / mL organic germanium treated group compared with the control group. In addition, embryo development ability to total cell number in blastocysts was significantly higher in the 200 ㎍ / mL organic germanium treated group than in the control group.
In order to evaluate the effect of the supplemented organic germanium on the mature medium, the inconvenience rate of the second-day in vitro fertilization (IVF) embryo is shown in Fig. 3 (a) and the percentage of the IVF embryo developed in the 7th blastocyst stage is shown in Fig. 3 (b). Here, Ear BL (early blastocyst), Exp BL (expanded blastocyst), and Hat BL (hatched blastocyst).
As shown in FIG. 3 (a), in the case of the 2-3 g IVF embryo treated with 200 g / mL organic germanium compared to the control group on
The effect of organic germanium supplemented to the maturation medium on the sperm permeability of in vitro matured porcine oocytes after 10 hours of sperm injection is shown in Table 4.
As shown in Table 4, monoclinic fertilization and fertilization efficiencies were significantly higher in the G-132 treated group than in the control (G-132 untreated group).
Experimental Example 3. Effect of organic germanium supplemented to mature medium on gene expression in oocyte and cumulus cells
DNA repair-related and antioxidant-related, and for cells to evaluate the effects of organic germanium supplement in maturation medium for the expression of suicide genes, respectively, in the oocyte and cumulus cells PCNA, POU5F1, Nrf-2, Bax, Bcl-2, And caspase-3 GAPDH (control group) were measured and shown in Figs. 4 (a) and 4 (b).
As shown in FIG. 4 (a), Nrf-2 transcript levels in oocytes were significantly higher in the 100 μg / mL and 200 μg / mL organic germanium treated groups than in the control group. In addition, the level of Bax transcription decreased gradually as the concentration of organic germanium increased.
As shown in FIG. 4 (b), PCNA transcript levels in cumulus cells were significantly higher in the 100 g / mL organic germanium treated group than in the control group. In addition, the level of Nrf-2 transcription increased gradually as the concentration of organic germanium increased.
As a result, it was confirmed from the above results that organic germanium plays an important role in in vitro fertilization during in vitro maturation through antioxidant and anti-cell suicide.
The primers used for the gene expression analysis are shown in Table 5.
PCNA
POU5F1
Nrf-2
Bax
Bcl-2
Caspase-3
R: 3'-TTGACGAAGTGGTCGTTGAG-5 '
F: 5'-CCTGTGCAAAAGATGGAGTG-3 '
R: 3'-GGAGAGAGTGGAGTGGCTTTT-5 '
F: 5'-GCGGACAAGTATCGAGAACC-3 '
R: 3'-CCTCAAAATCCTCTCGTTGC-5 '
F: 5'-CCCATTCACAAAAGACAAACATTC-3 '
R: 3'-GCTTTTGCCCTTAGCTCATCTC-5 '
F: 5'-TGCCTCAGGATGCATCTACC-3 '
R: 3'-AAGTAGAAAAGCGCGACCAC-5 '
F: 5'-AGGGCATTCAGTGACCTGAC-3 '
R: 3'-CGATCCGACTCACCAATACC-5 '
F: 5'-CGTGCTTCTAAGCCATGGTG-3 '
R: 3'-GTCCCACTGTCCGTCTCAAT-5 '
187
200
71
199
193
186
XM_003359883
NM_001113060
Toxicology 2009; 265: 69-79
XM_003127290
NM_214285
NM_214131
Claims (15)
Wherein the carboxyethyl germanium sesquioxide is present in an amount of 0.01 to 20% by weight of the total weight of the polymer.
Wherein the polymer is at least one selected from the group consisting of polyurethane, polycarbonate, silicone, polyethylene, polypropylene, polyimide, polyester, polysulfone, polyvinyl chloride, latex and polyvinyl alcohol. .
Wherein the combination further comprises an antioxidant, an antibacterial agent, an anti-inflammatory agent or a combination thereof.
The antioxidant may be selected from the group consisting of resveratrol, nordihydroguaiarectic acid, viniferin, quercetin, fisetin polyphenol, butein, Wherein the catheter is at least one selected from the group consisting of piceattonol, isoliquiritigenin, vitamin and tocopherol.
The antimicrobial agent may be an organic antimicrobial agent composed of a phenylcylin type, a cephalosporin type, an aminoglycoside type, a chloramphenicol type, a tetracycline type, a macrolide type, a lincomomycin type, a polyamic type, a fluoroquinoline type, Wherein the inorganic antibacterial agent is at least one selected from the group consisting of inorganic antibacterial agents composed of chromium, titanium dioxide, and zeolite.
The anti-inflammatory agent may be selected from the group consisting of glycyrrhizic acid, glycyrrhetic acid, allantoin, azulene, mefenamic acid, phenylbutazone, indomethacin, Ibuprofen, ketoprofen, epsilon-aminocaproic acid, hydrocortisone, panthenol, zinc oxide, diclofenac sodium, and the like. ), Aloe extract, beefsteak plant extract, mugwort extract, camomile extract, comfrey extract, sanguisorba root extract and water-cress extract from the group consisting of aloe extract, beefsteak plant extract, mugwort extract, camomile extract, Lt; RTI ID = 0.0 > 1, < / RTI >
Wherein said catheter has antioxidant or anti-cellular suicide function.
Wherein the catheter expresses the Nrf-2 gene or inhibits the expression of the Bax gene.
Wherein the catheter is for in vitro fertilization.
Wherein the catheter is a urethral drain catheter, a balloon catheter, a Hikman catheter, an organ catheter, a dental turn-around catheter, a liposuction catheter, or a cervical catheter.
Molding the formulation into a tube shape; And
And coating the surface of the formulation with carboxyethyl germanium sesquioxide.
Wherein the catheter body is tubular.
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Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2008238157A (en) | 2007-03-28 | 2008-10-09 | Waters Co Ltd | Filter for water cleaner containing organic germanium, and method of manufacturing the same |
WO2011068545A1 (en) | 2009-12-03 | 2011-06-09 | Searete Llc | Systems, devices, and methods including catheters configured to monitor and inhibit biofilm formation |
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Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2008238157A (en) | 2007-03-28 | 2008-10-09 | Waters Co Ltd | Filter for water cleaner containing organic germanium, and method of manufacturing the same |
WO2011068545A1 (en) | 2009-12-03 | 2011-06-09 | Searete Llc | Systems, devices, and methods including catheters configured to monitor and inhibit biofilm formation |
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