JP5131632B2 - Drug sustained-release material and method for producing the same - Google Patents

Description

  The present invention relates to a drug sustained-release material designed for sustained release of a drug and a method for producing the same, which can be used in fields such as the pharmaceutical industry and the food industry.

  The drug delivery system (DDS) is a system for allowing a necessary drug to act at a necessary site at a necessary time, and by using this system, side effects due to an excessive drug can be prevented and the drug It is expected that a high therapeutic effect can be obtained by acting only on the target site.

  In order to put the drug delivery system into practical use, it is essential to develop a drug sustained release material for sustained release of the drug. Currently, drug sustained-release tablets, drug-release fine particles and implantable preparations for oral administration have been developed as sustained-release materials.

  However, drug sustained-release tablets for oral administration are limited to drugs that can be administered orally, and there is a problem that local administration of drugs is impossible. In addition, drug-release fine particles for injection and conventional implantable preparations have a problem that they cannot be produced unless they undergo complicated steps. Furthermore, when the drug-released fine particles are used to act locally on the operated site, it is difficult to fix the fine particles to the incised portion because the tissue regeneration of the incised portion is insufficient.

In addition, as a drug sustained-release material, Patent Document 1 discloses a calcium sulfate-polymer complex, Patent Document 2 discloses a bone morphogenetic protein; a porous particulate polymer matrix; a bone clot protein sequestration blood clot; and sulfuric acid. A composition comprising a calcium hemihydrate containing material is disclosed. Patent Document 3 discloses a layered drug delivery device comprising a water-soluble adhesive layer, a non-adhesive bioerodible backing layer, and optionally one or more drugs in either or both layers, Patent Document 4 discloses a solid pharmaceutical composition comprising a pharmaceutically active ingredient, a hydrophilic surfactant, a lipophilic surfactant, and triglyceride.
JP-T-2001-517613 JP-T-9-502368 JP 2005-504663 A Special table 2003-517470 gazette

  However, these sustained-release materials disclosed in Patent Documents 1 to 4 have a problem that the production method is complicated and the material strength may be insufficient.

  In view of the above problems, an object of the present invention is to provide a novel sustained-release material and a method for producing the same, which can be easily prepared and have sufficient material strength.

  As a result of various studies to achieve the above problem, by utilizing the phenomenon that gel preparation is difficult due to precipitation caused by mixing a negatively charged gelled material with alginic acid and a positively charged drug, By combining these with a porous material, it was found that a gel can hold a drug, and a sustained-release drug material in which the porous material maintains the strength of the material and the material strength is improved can be easily obtained, and the present invention is completed. I let you.

That is, the drug sustained-release materials of the present invention, after dipping the porous material in an aqueous solution of a drug having a positive charge, the concentration is immersed in an aqueous solution of alginate 2-2.5 wt%, then, calcium chloride solution It was created by gelling alginic acid by immersing in an aqueous solution .

In addition, the drug is any one of gentamicin, kanamycin, and streptomycin.

  Furthermore, the porous material is a biodegradable porous film.

Method of manufacturing a sustained drug release materials of the present invention, after dipping the porous material in an aqueous solution of a drug having a positive charge, the concentration is immersed in an aqueous solution of alginate 2-2.5 wt%, then, calcium chloride It is characterized by gelling alginic acid by dipping in a solution .

  ADVANTAGE OF THE INVENTION According to this invention, the drug sustained release material which can be produced simply and has sufficient material strength, and its manufacturing method can be provided.

  The drug sustained-release material of the present invention is obtained by immersing a porous material in an aqueous solution of a drug having a positive charge, then immersing it in an aqueous solution of a gelled material having a negative charge, and then gelling the gelled material. It was produced by. Hereinafter, the method for producing the sustained-release drug material of the present invention will be described.

  First, the porous material is immersed in an aqueous solution of a drug having a positive charge.

  The porous material used in the present invention is not limited to a specific material and can be selected according to the required material strength and application. For example, a biodegradable porous membrane, polyurethane foam, or the like can be used. Also, the material of the biodegradable porous membrane is not limited to a specific material. For example, poly-L-lactic acid (PLLA), poly-ε-caprolactone (PCL), 3-hydroxybutyric acid-3-hydroxyvaleric acid -A copolymer (PHBV) etc. can be used individually or in mixture.

  The drug used in the present invention is not limited to a specific drug as long as it has a positive charge in an aqueous solution, and can be selected according to the application. Preferably, those having a positive charge of 2 or more are used in order to generate a gelled material and an aggregate having a negative charge to enhance the sustained release of the drug. As such a drug, for example, antibiotics such as gentamicin, kanamycin, and sprepomycin can be used.

  Next, the porous material is taken out from the aqueous solution of the drug and immersed in an aqueous solution of the gelling material having a negative charge. Here, on the surface and inside of the porous material, positive and negative charges act between a drug having a positive charge released from the inside and a gelled material having a negative charge entering from the outside. As a result, aggregates are formed.

  The gelling material used in the present invention is not limited to a specific one as long as it has a negative charge in an aqueous solution, but preferably alginic acid is used.

  Thereafter, the gelled material is gelled. When alginic acid is used as the gelling material, the porous material is taken out of the aqueous solution of alginic acid and immersed in an aqueous solution containing alkaline earth metal ions, for example, an aqueous solution of calcium chloride, to promote gelation.

  When alginic acid is used as the gelling material, the concentration of alginic acid in the aqueous solution is preferably 2% by mass or more. If it is less than 2% by mass, the drug release rate from the drug sustained-release material is too fast, so that effective sustained-release properties cannot be obtained.

  The drug sustained-release material of the present invention obtained as described above makes it possible to retain the drug on the gel by utilizing the fact that precipitation occurs when a gelled material having a negative charge and a drug having a positive charge are mixed. ing. Further, the gelling material and the drug are combined with the porous material to maintain the strength of the material in the porous material. Therefore, according to the present invention, it is possible to provide a drug sustained-release material having an excellent sustained-release property of a drug and sufficient material strength.

  And according to the manufacturing method of the drug sustained-release material of this invention, a drug sustained-release material can be produced simply.

  Further, when a biodegradable porous membrane is used as the porous material, there is an advantage that it is not necessary to take out after being embedded in the body by surgery.

  FIG. 1 shows a schematic diagram of an embodiment of the sustained-release drug material of the present invention using alginic acid as the gelling material and gentamicin as the drug. FIG. 1 shows that gentamicin is retained in alginic acid by the interaction between the negative charge of alginic acid and the positive charge of gentamicin in the porous material. In addition, it shows that alginic acid is gelled by the interaction between the negative charge of alginic acid and the positive charge of calcium ions.

  The present invention is not limited to the above embodiment, and various modifications can be made without departing from the spirit of the present invention.

  A drug sustained-release material according to the present invention was prepared using the antibiotic gentamicin, and an antibacterial test using an agar plate containing E. coli was performed.

  A biodegradable polyester porous membrane was used as the porous material. This porous membrane was prepared by mixing poly-L-lactic acid (PLLA) and poly-ε-caprolactone (PCL) at a mass ratio of 1: 4 and using a thermally induced phase separation method.

  A porous membrane (5 × 5 × 1 mm) is immersed in a gentamicin solution overnight and then gelled by immersion in a sodium alginate solution of various concentrations for 1 hour and further in a calcium chloride solution overnight. Produced.

  The amount of drug released was determined from the diameter of the growth inhibition circle using an agar plate method using Escherichia coli K12 as an indicator bacterium.

  The test was performed by changing the agar plate every day.

  As shown in FIG. 2, in the porous body that was not gelled and impregnated only with the drug, a large amount of the drug was released in the initial stage, and the released amount rapidly decreased in the first 4 days. On the other hand, when gelation was performed using calcium alginate, it was shown that the drug release in the initial stage was suppressed and the drug was gradually released over 6 days. In particular, when the alginic acid concentration was 2% by mass, the decrease in the release amount was the smallest, and when the concentration was 2.5% by mass, the decrease in the release amount was small.

  An antibacterial test was conducted in the same manner as in Example 1 except that a commercially available sponge (polyurethane foam) cut into a thickness of 1 mm was used as the porous material.

  As shown in FIG. 3, the same result as in Example 1 was obtained.

It is a schematic diagram of one Embodiment of the drug sustained release material of this invention. 2 is a graph showing changes with time in the amount of gentamicin released in Example 1. FIG. 6 is a graph showing changes with time in the amount of gentamicin released in Example 2. FIG.

Claims (4)

By immersing the porous material in an aqueous solution of a positively charged drug, then immersing it in an aqueous solution of alginic acid having a concentration of 2 to 2.5% by mass , and then immersing it in a calcium chloride solution to gel the alginic acid . A drug sustained-release material characterized by being produced. The drug, gentamycin, kanamycin, sustained drug release material according to claim 1, wherein a is either spray script clarithromycin. The drug sustained-release material according to claim 1 or 2 , wherein the porous material is a biodegradable porous membrane. The porous material is immersed in an aqueous solution of a positively charged drug, then immersed in an aqueous solution of alginic acid having a concentration of 2 to 2.5% by mass , and then immersed in a calcium chloride solution to gel the alginic acid. A method for producing a sustained-release drug material.

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