KR20000040011A - Manufacturing device of medical supplies' bead and manufacturing method thereof - Google Patents

Abstract

PURPOSE: A manufacturing device of medical supplies' bead and a manufacturing method thereof are provided which are to manufacture a large quantity of the medical supplies' bead containing heat-unstable medical supplies such as antibiotic. CONSTITUTION: A device comprises: (i) a cooling injection device(1); and (ii) a bead molding device(2), wherein the cooling injection device(1) comprises: (a) a cooling portion(20) which cools a mixture of medical supplies, cement for medical treatment and liquid monomer(10); (b) a transferring portion(11) which is curved on the lower end of the cooling portion(20) and is formed as a pipe-shape; (c) a nozzle(22) which molds the mixture in fixed diameter; (d) a freezing portion(21); and (e) a cutter(30), and the bead molding device(2) comprises: (a) a container(60) which stores the cut mixture; (b) a spherical shape mold(51); (c) a pair of transferring rollers(R2, R3); and (d) a pressure roller(R1). The method comprises: (i) putting a mixture of medical supplies, cement for medical treatment and methylmethacrylate in the cooling portion; (ii) freezing the mixture; (iii) cutting the frozen mixture into fixed size; (iv) supplying the cut mixture mold to the spherical mold and pressurizing it with the pressure roller to prepare medical supplies' bead.

Description

Drug Bead Manufacturing Device and Process for Producing the Drug Bead

The present invention relates to a pharmaceutical bead manufacturing apparatus and a manufacturing method, and more particularly, the mixture kneading of pharmaceutical and medical cement and liquid monomer has high viscosity and fluidity, so that injection is not good, or the mixture is solidified and then separated from the mold. It eliminates the functional defects of the existing bead manufacturing method, such as preventing the degradation of product quality and productivity in the manufacturing process of pharmaceutical beads, and at the same time, the mold is manufactured in the form of a roller to continuously produce the product. It is to provide a manufacturing method and an apparatus thereof which make it possible.

Beads containing antibiotics have significant implications for reducing systemic side effects and enhancing their effectiveness by ensuring that antibiotics, effective for the treatment of acute and chronic osteomyelitis and musculoskeletal system infections, are delivered directly to the lesion. have. In addition, chronic osteomyelitis and periarticular prosthetic infections were known to be caused by acute osteomyelitis in the past, but now patients with chronic osteomyelitis due to increased traffic accidents and industrial accidents, or accompanying sequelae of open fractures The trend is increasing (Korean Journal of Orthopedic Surgeons, 24: 549-556, 1989). For the treatment, the treatment is mainly performed by systemic therapy of antibiotics, but the frequency of recurrence is very high even after the treatment, and it is resistant to treatment due to the abuse of antibiotics. Increased resistance, systemic toxicity and side effects are one of the hardest to treat in the orthopedic field. Many treatment methods have been proposed to solve this osteomyelitis. Among them, bone shunting has been used for a long time as a surgical method for surgically removing the necrosis of the infected bone. At this time, the generated lung space may be filled with beads containing antibiotics to fill the pores and to prevent recurrence due to the medicinal effects of antibiotics continuously released from the beads. Septopal (E. Merch), an antibiotic bead, is melted at a high temperature (150 ° C. to 160 ° C.) in an injection molding machine by mixing a powder containing antibiotics gentamycin and cement based polymethylmethacrylate (PMMA). A method of injection molding in a mold is used. This method has the advantage of making beads with a diameter of 4mm or 7mm easily, but the antibiotics are exposed to high temperatures in the manufacturing process, which reduces the titer of antibiotics and has the weakness of decomposition products. Not a suitable way to make beads.

Table 1 below shows the decrease in antibiotic titer and the formation of degradation products under high temperature storage conditions.

Reduction of antibiotic titer and degradation product generation after storage at 150 ° C. for 25 minutes and 60 minutes division Test Methods Titer (μg / mg) Remarks Control 150 ° C, 25 minutes 150 ° C., 60 minutes Gentamicin sulfate Bio Assay 617 586 (95.0%) 531 (86.1%) Hydrochloric acid vancomycin Bio Assay 1005.9 793.7 (78.9%) 701.9 (69.8%) Liquid chromatography 1001.8 751.6 (75.0%) 697.2 (69.6%) Degradation peaks found Sephazoline Sodium Bio Assay 848.9 732.5 (86.3%) 687.2 (81.0%) Liquid chromatography 856.7 734.0 (85.7%) 699.7 (81.7%) Degradation peaks found

As another method for making antibiotic beads, Korean Patent Application No. 94-1632 and Japanese Patent No. 25,945,294 evenly mix antibiotics with medical cement (polymethacrylate) and then add liquid monomers (methylmethacrylate monomers) to the mixture. It is proposed to prepare a bead by cutting into a bead of a suitable size in the state of mixing and hardening. This method maintains the titer of the antibiotic by working at room temperature, but it is not suitable for producing large amounts of beads because the time required for the powder mixture and liquid monomer to fully react and solidify is within 10 minutes.

In addition, Arthur B. Flick (Clinical Orthopaedics and Related Research, 223, 282-286, 1987) also used a disposable syringe with a Teflon-coated stick on cold rolled steel to inject and solidify the mixture by injecting the mixture directly. Shows how to separate the beads. However, in this method, when the mixture is injected directly into the molding machine through a disposable syringe, when the mixture has a high viscosity and poor fluidity, the injection is not performed because the nozzle diameter of the syringe is small, or the pressure is applied to the syringe nozzle. In the state where the cement and the liquid monomer do not completely react, there are disadvantages in that properties such as the hardness and dissolution rate of the beads may vary depending on the injection time due to phase separation between the mixed powder of the antibiotic and the medical cement and the liquid monomer. In addition, since the mixture of antibiotic, medical cement and liquid monomer is directly injected into the mold, the beads do not fall well from the pressure roller after the mixture is completely solidified. It is inconvenient to produce the product continuously because of the process.

The present invention has been made to solve the above-described problems, the object of the present invention is to provide a cooling unit for cooling a mixture of medicines, medical cement and liquid monomer, a conveying portion bent at the lower end of the cooling portion and formed in a pipe shape, and the conveying portion. A cold injection device comprising an extended nozzle to form the mixture into a predetermined diameter, a freezing unit surrounding the outer shape of the nozzle, a cutting machine located under the nozzle to cut the mixture, and a cut mixture; A bead forming apparatus comprising a container to be formed, a spherical mold formed from a plurality of opposing hemispherical molds, a roller for transporting each hemispherical mold, a press roller for pressing the transferred mold from both sides, and the apparatus Including the manufacture of pharmaceutical beads from a dough made of a mixture of medicines and monomers of medical cement and liquid In particular, the cutter is rotated about an axis to cut the mixture from the nozzle into pellets of a certain length, and the mold is made of plastic and coated with an oily material so that the beads are easily separated from the mold. And, the pressure roller is provided with a plurality of symmetrically formed, to rotate in the opposite direction to compress the mold and the medical cement is polymethyl methacrylate, methyl methacrylate- methacrylate copolymer, poly [ Methyl methacrylate-co-styrene] copolymers are characterized by mixing one or more of them.

1 is an explanatory view showing a cold injection device and a bead forming device for making a pellet-shaped mixture in the present invention;

2, 3 and 4 are perspective views illustrating a method for easily separating the mold and the beads using a spherical mold made of a plastic material according to the present invention

Explanation of symbols for main parts of the drawings

1: Cooling injection device 2: Bead molding device

10: pharmaceutical powder, medical cement and liquid monomer mixture

11: transfer unit 20: cooling unit

21: Frozen 22: Nozzle

23: rotating shaft 30: cutting machine

40: mixture in pellet form 50: globular mold

51: hemispherical mold 52: iron core groove

53: half sphere groove 60: mixture container

70: medical core 90: bead

R1: pressure roller R2: feed roller 1

R3: Feed Roller 2

In one aspect, the present invention provides a cooling unit for cooling a mixture of pharmaceuticals, medical cement and liquid monomers; A conveying part bent at the lower end of the cooling part and formed to have a pipe shape; A nozzle extending to the conveying portion to mold the mixture to a predetermined diameter; A freezing unit provided surrounding the outer shape of the nozzle; A container for storing the mixture cut in the cooling injection device and the cooling injection device comprising a cutter positioned under the end of the nozzle to cut the mixture; Globular mold formed by a plurality of opposing hemispherical molds; A roller for conveying each hemispherical mold; Provided is a bead manufacturing apparatus, characterized in that consisting of a bead molding device consisting of a pressure roller for pressing the transferred mold on both sides.

In another aspect, the present invention is to put a mixture of medicine, medical cement and methyl methacrylate to the cooling unit, lower the conveying unit and the extended nozzle to a certain temperature through the freezing unit to freeze the mixture, and then molded to a certain size by a cutter, Provided is a method for producing a pharmaceutical bead characterized in that the pharmaceutical beads are produced by supplying a spherical mold and applying pressure with a pressure roller.

Hereinafter, preferred embodiments of the present invention will be described with reference to the accompanying drawings.

1 illustrates a method and apparatus according to a process working as an explanatory view showing a cold injection apparatus 1 and a bead forming apparatus 2 for making a pellet-shaped mixture in the present invention. First, medicines, especially antibiotics, medical cement and liquid monomers are mixed at a low temperature, and then the mixture is transferred by the transfer part 11, and the cylinder is large and long enough to have a diameter of about the final bead diameter as shown in the upper left of the figure. Passing through the nozzle 22 and injecting it into a cylindrical shape, the mixture is cut by the cutter 30 to a certain length to be the same volume as the final bead volume to form a mixture 40 in pellet form. During the transfer, the temperature is maintained at 0 ° C. by the cooling unit 20 to delay the solidification of the mixture. In the nozzle 22 part, the temperature is maintained at −20 ° C. by the freezing unit 21 to suppress the reaction of the mixture as much as possible. It is configured to. If the temperature of the pellet mixture 40 is increased to 0 ° C., it can be remolded into a desired shape, so that the mixture 40 can be used in a roller-shaped mold prepared in advance. When the temperature of the mixture is 0 ° C, the solidification time is longer than 1 hour, especially when the temperature of the mixture is lowered to -20 ° C, so that the solidification time is extended by 24 hours or more. There are advantages that can be placed, and the titer per bead of the prepared antibiotic was 80% to 120% relative to the initial value, it was possible to maintain the titer of the antibiotic. In addition, the beads prepared by this method were well injected even when the viscosity of the liquid monomer was small due to the high viscosity, and the pressure applied to the nozzle was small so that the phase separation of the powder and the liquid did not occur.

Described the method and apparatus for continuously producing beads using a mold, the existing manufacturing method is a long rectangular mold with a plurality of hemispherical grooves formed in a straight line, which is connected to 15, 30 or more iron cores. When manufacturing, each mold had to be different in length, and the number of nozzles of the injection molding machine had to be changed according to the number of hemispherical grooves formed in the mold, which caused problems. In order to eliminate the problems of the conventional manufacturing method, two pressure rollers (R1) having several hemispherical grooves are rotated in opposite directions on both sides, and a spherical mold 50 and a medical iron core (between) are disposed therebetween. The device is designed so that 70 is simultaneously supplied through the feed rollers R2 and R3, and the mixture 40 in pellet form is continuously supplied from the container 60 with the freezing section 21 to be compression molded in a pressure roller. Continuous bead production was made possible. At this time, the pressure roller (R1) serves to press the pressure so that the mixture is molded into a bead shape, the spherical mold 50 serves to maintain the bead shape while the mixture is solidified. The final product produced through this device is spherical mold (50) encapsulated in a bead, solidified at room temperature, then packaged and finished as a finished product, cut into 15, 30 or more units and can be packaged. In addition, it can be cut and used to the desired length at the site where the bead is used by packing in roll form, and there is an advantage of not having to make several molds according to the number of beads connected. Beads prepared in this way can be used after peeling off the outer packaging and peeling the globular mold 50 when using the product.

2, 3 and 4 illustrate a method for easily separating beads from a spherical mold made of a plastic material such as polypropylene resin in the present invention. Existing bead manufacturing methods include antibiotics, medical cement and liquids. Since the mixture of the monomer is injected directly into the mold and the mixture is solidified in the mold, the mold cannot be reused during the time of solidification, and it is difficult to separate the solidified beads from the mold after the mixture is solidified. Mixture residue remained in the mold, making it impossible to reuse without washing, causing problems in continuous mass production.

The present invention uses the method of solidifying in the spherical mold 50 of plastic material in order to eliminate the problems of the existing manufacturing method by separating the mold and the mold 50 together from the mold after the mixture is solidified It allows for continuous use without washing. In addition, since the globular mold 50 itself surrounds the beads, there is an advantage in helping to maintain a sterile state during packaging. The spherical mold 50 can be easily separated from the beads when the product is used, and has an advantage of being more easily separated by coating with an oily material, in particular, silicone oil.

The above-described mold 50 is made of a plastic resin, and in particular, the polypropylene resin does not react with a mixture of antibiotics, medical cement and liquid monomers, and when it is made thin, it can be bent well and maintain the original mold form well. Suitable for making molds. In addition, as shown in FIG. 4, the grooves 51 into which the medical core can be inserted into the mold 50 are made to produce beads connected to the medical core.

The present invention configured as described above does not wash the mold by separating the beads and the mold together after the mixture is solidified using a method of solidifying the mixture in a thin mold made of plastic as described above in the apparatus and method for manufacturing a pharmaceutical bead. Continuous use is possible without. In addition, since the globular mold itself surrounds the beads, there is an advantage in helping to maintain sterility even when packaging. These thin molds can be easily removed from the beads when the product is in use, and can be easily removed by pre-coating with oily material, especially silicone oil.

Claims (6)

A cooling unit for cooling the mixture of medicines, medical cement and liquid monomers; A conveying part bent at the lower end of the cooling part and formed to have a pipe shape; A nozzle extending to the conveying portion to mold the mixture to a predetermined diameter; A freezing unit provided surrounding the outer shape of the nozzle; Cooling injection device consisting of a cutting machine located in the lower end of the nozzle to cut the mixture; A container for storing the mixture cut in the cold injection device; Globular mold formed by a plurality of opposing hemispherical molds; A roller for conveying each hemispherical mold; Pharmaceutical device bead manufacturing apparatus characterized in that consisting of a bead forming device consisting of a pressure roller for pressing the transferred mold on both sides. According to claim 1, wherein the cutter is a bead manufacturing apparatus, characterized in that for cutting the mixture coming out of the nozzle in a pellet shape of a predetermined length by rotating about a axis located below the nozzle end. According to claim 1, wherein the hemispherical mold is pharmaceutical beads manufacturing apparatus, characterized in that the iron core groove is formed to connect each hemisphere groove. The apparatus of claim 1, wherein the globular mold is made of plastic and coated with an oily material so that beads can be easily separated from the mold. The mixture of medicine, medical cement and methyl methacrylate is placed in the cooling section, the conveying section and the extended nozzle are lowered to a certain temperature through the freezing section to freeze the mixture, and then formed into a certain size by a cutting machine, and supplied to a spherical mold. A pharmaceutical bead manufacturing method, wherein the pharmaceutical beads are manufactured by applying pressure with a roller. 6. The mixture according to claim 5, wherein the medical cement is one or a mixture of two or more selected from the group consisting of polymethylmethacrylate, methylmethacrylate-methylacrylate copolymer, and poly [methylmethacrylate-co-styrene] copolymer Pharmaceutical beads manufacturing method characterized in that.