KR101669647B1 - A bioabsorbable radio-opacity marker composition and a surgical article having the same - Google Patents

Abstract

The present invention relates to a radiopaque marker composition for bioabsorption and a surgical article comprising the same. The radiopaque marker composition for bioabsorption according to the present invention is characterized by containing iodine, xenon or a combination thereof. When the surgical article according to the present invention is used, the position of the stent or the like in the human body can be accurately tracked.

Description

TECHNICAL FIELD [0001] The present invention relates to a radiopaque marker composition for bioabsorption, and a surgical article comprising the same. BACKGROUND ART < RTI ID = 0.0 >

The present invention relates to a radiopaque marker composition for bioabsorption and a surgical article comprising the same. More particularly, the present invention relates to a radiation-impermeable marker composition for bioabsorption which can be used for accurately grasping the position of a stent or the like through radiation such as an x-ray or a gamma ray after a stent is implanted, and a surgical article containing the same.

Stent is a luminal dilatation mechanism used to expand a narrowed passage due to stenosis, and is widely used for the treatment of cancer or vascular disease.

However, metal stents used in vivo are magnesium, potassium, calcium, titanium, chromium, iron, cobalt and nickel and their alloys are used as biocompatible metal materials. These metal materials are short as 3-4 periodic atoms in the periodic table Radiations such as x-rays (10 to 0.01 nanometers) or gamma rays (0.01 to 0.00001 nanometers) with wavelengths can easily be transmitted. Furthermore, recently, biodegradable polymers used in drug-releasing stents and biodegradable polymer stents are also permeable to radiation, so that it is impossible to specify the location of the biodegradable polymer when it is transplanted into a human body.

In order to solve this problem, a method of attaching metal radiopaque material of at least five cycles such as gold, platinum, tantalum, tungsten, or thunium to the specific region of the stent is used to confirm its position. In order to combine these metal-radiopaque materials with the stent, additional space is required in the stent, and a process of bonding the metal-radiopaque marker to the stent is required.

Moreover, when these metal radiopaque markers are implanted into the human body, only a portion where the metal radiopaque markers are installed can be confirmed definitively. In addition, when metal-impermeable markers are installed on a biodegradable stent made of a biodegradable polymer, metallic radiopaque markers such as gold, platinum, tantalum, tungsten, and thallium, which have non-degradable characteristics in vivo, It may cause a problem of a foreign body reaction in the living body, and if the metal radiopaque marker attached to the stent is removed, it may cause other problems because it circulates in vivo without being discharged outside the living body.

Korean Patent Publication No. 10-2014-0111602 (Apr. 19, 2014) Korean Patent Publication No. 10-2011-00046394 (May 04, 2011)

The present invention provides a radiopaque marker composition for bioabsorption and a surgical article comprising the same.

One aspect of the present invention may be a bioabsorbable radiopaque marker composition comprising iodine, xenon, or a combination thereof.

In this aspect, the iodine source providing iodine is selected from the group consisting of iodine, hydrogen iodide, sodium iodide, potassium iodide, cesium iodide, cesium iodide, potassium iodate, sodium periodate, calcium iodide, copper iodide and povidone iodine And the xenon source that provides the xenon may include at least one selected from the group consisting of an iuprourinized xenon, a tetrafluorinated xenon, and a hexofluorinated zenon.

This aspect may further include a biodegradable polymer.

In this aspect, the biodegradable polymer may be in a state dissolved in a hydrophilic solvent.

In this aspect, the solvent is selected from the group consisting of water; Alcohols including methanol, ethanol, propanol, butanol, pentanol, heptanol, hexanol, octanol, nonanol and decanol; Aldehydes including ammonia, dimethylsulfoxide, dimethylformamide, acetonitrile, tetrahydrofuran, formaldehyde, glutaraldehyde and acetaldehyde; Alkanes including dioxane, chloroform, heptane, hexane, pentane, octane, nonane and decane; Benzene ring-type solvents including benzene, toluene and xylene; Ethers, including ethers, di-propyl ethers, petronium ethers and methyl-t-butyl ethers; Ketones including propanone, butanone, pentanone, hexanone and heptanone; Methylene chloride, trifluoro isopropane, and carbon tetrachloride.

In this aspect, the biodegradable polymer is selected from the group consisting of poly-L-lactide, poly-D-lactide, poly-D, L-lactide, polyglycolide, polycaprolactone, poly- Poly-D-lactide-co-glycolide, poly-D, L-lactide-co-glycolide, poly-L-lactide-co-caprolactone, poly- -co-caprolactone, poly-D, L-lactide-co-caprolactone, polyglycolide-co-caprolactone, polydioxanone, polytrimethylene carbonate, polyglycolide- Amide esters, polypeptides, polyorthoesters, polymaleic acid, polyphosphazenes, polyanhydrides, polyseva cyanide hydrides, polyhydroxyalkanoates, polyhydroxybutyrates, polycyanoacrylates, Cellulose acetate butyrate, cellulose triacetate It may include at least one selected from the group consisting of a copolymer thereof.

In this aspect, the content of the biodegradable polymer may be 0.01 to 90% by weight based on the total weight of the composition.

In this aspect, the total content of iodine and xenon may be from 0.01 to 95% by weight based on the total weight of the composition.

Another aspect of the present invention is a surgical article comprising the composition, and more particularly, a stent or a polymer screw coated with the composition, a biodegradable polymer stent including the composition, a scaffold or a surgical suture have. The surgical article may be a tissue regeneration support, a bio-nanofiber, a hydrogel, a bio-sponge, a pin, a screw, a screw, a rod, a filler, an implant or a living body implant.

According to the present invention, it is possible to provide a bioabsorbable radiopaque marker composition which can not transmit radiation such as X-rays and can act as a radiopaque marker in the human body.

When the surgical article according to the present invention is used, the position of the article in the human body can be accurately tracked.

Hereinafter, preferred embodiments of the present invention will be described. The embodiments of the present invention can be modified into various other forms, and the scope of the present invention is not limited to the embodiments described below. Embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art.

The radiopaque marker composition for bioabsorption according to one aspect of the present invention may include iodine, xenon, or a combination thereof.

Iodine may be provided from an iodine source. Specifically, it may be provided from a compound containing solid iodine or iodine. The iodine-containing iodine compound may include hydrogen iodide, sodium iodide, potassium iodide, methyl iodide, cesium iodide, potassium iodate, sodium periodate, calcium iodide, copper iodide, povidone iodide or a combination thereof. The iodine compound may be completely dissolved in the ionic state, or may be present in a compound state when a part of the iodine compound is not dissolved.

Xenon may be provided from a xenon source. Specifically from compounds containing xenon gas or xenon. The xenon-containing xenon compounds may include an europurinized xenon, a sulfurized xenon, a hexofluorinated zenon, or a combination thereof. The xenon compound may be dissolved and present in a completely ionic state, or in a compound state when a part of the compound is not dissolved.

When the radiopaque marker composition for bio-absorption of this aspect is irradiated with X-rays, the X-ray can not be transmitted. The reason for this is that the iodine and the xenon are large in size. Therefore, for example, when the stent coated with the composition of the present aspect is used, it is possible to accurately grasp the position and the like of the stent through X-ray imaging, thereby enabling the follow-up observation. X-rays are generally used in medical applications. X-rays have a wavelength range of 0.01 to 10 nanometers or gamma rays have a wavelength range of 0.00001 to 0.01 nanometers.

Iodine, xenon and the compounds thereof are water; Alcohols such as methanol, ethanol, propanol, butanol, pentanol, heptanol, hexanol, octanol, nonanol, decanol; Aldehydes such as ammonia, dimethylsulfoxide, dimethylformamide, acetonitrile, tetrahydrofuran, formaldehyde, glutaraldehyde and acetaldehyde; Alkane solvents such as dioxane, chloroform, heptane, hexane, pentane, octane, nonane and decane; Benzene cyclic solvents such as benzene, toluene and xylene; Ether solvents such as ether, di-propyl ether, petronium ether and methyl-t-butyl ether; Ketone solvents such as propanone, butanone, pentanone, hexanone and heptanone; Methylene chloride, trifluoro isopropane, carbon chloride, and the like, the above materials can be used as a solvent.

In addition, iodine, xenon, and compounds thereof are easily absorbed or excreted in vivo. Therefore, unlike metal-impermeable markers such as gold, platinum, tantalum, tungsten, and thallium, they do not remain in the living body and are discharged outside the body.

In addition, a conventional metal radiopaque marker is required to be mounted on a stent by designing and installing the same. According to this aspect, since this process is not necessary, the manufacturing process can be simplified by simplifying the process.

The composition of this aspect may be a bioabsorbable radiopaque marker composition for stents that can be applied to a stent. The iodine and iodine compounds, xenon and xenon compounds are radiation-impermeable substances that can be used in vivo. Astanthin (At) and radon (Rn) are non-metallic substances with 6 cycles and can act as impermeable markers in vivo because they are impermeable to radiation. However, they are harmful to living organisms and therefore, impossible to use.

The bioabsorbable radiopaque marker composition of this aspect may further comprise a biodegradable polymer. The biodegradable polymer is not particularly limited as long as it can be decomposed in the human body. As the biodegradable polymer, a synthetic biodegradable polymer or a natural biodegradable polymer can be used.

The biodegradable polymer is selected from the group consisting of poly-L-lactide, poly-D-lactide, poly-D, L-lactide, polyglycolide, polycaprolactone, poly- Poly-D-lactide-co-glycolide, poly-D, L-lactide-co-glycolide, Polylactide-co-caprolactone, polylactic acid-co-caprolactone, polydioxanone, polytrimethylene carbonate, polyglycolide-co-dioxanone, polyamide ester, , Polyorthoesters, polymaleic acid, polyphosphazenes, polyanhydrides, polysevae corn hydrate, polyhydroxyalkanoates, polyhydroxybutyrates, polycyanoacrylates, polydodamine, cellulose, cellulose Acetate butyrate, cellulose triacetate and their aerials And at least one polymer selected from the group consisting of coalescent polymers.

The molecular weight of the biodegradable polymer is preferably 1,000 to 3,000,000. When the molecular weight is less than 1,000, the polymer coating layer and the matrix can not be formed. When the molecular weight is more than 3,000,000, the molecular weight is too large and biodegradation of the polymer may not be performed.

The content of the biodegradable polymer may be 0.01 to 90% by weight based on the total weight of the composition. When the content of the biodegradable polymer is less than 0.01% by weight, the polymer coating layer and the matrix may not be formed. When the content of the biodegradable polymer is more than 90% by weight, the viscosity may become too high.

The biodegradable polymer may be dissolved in a solvent. The solvent is not particularly limited as long as it can dissolve the biodegradable polymer. Specifically, the solvent is water; Alcohols such as methanol, ethanol, propanol, butanol, pentanol, heptanol, hexanol, octanol, nonanol, decanol; Aldehydes such as ammonia, dimethylsulfoxide, dimethylformamide, acetonitrile, tetrahydrofuran, formaldehyde, glutaraldehyde and acetaldehyde; Alkane solvents such as dioxane, chloroform, heptane, hexane, pentane, octane, nonane and decane; Benzene cyclic solvents such as benzene, toluene and xylene; Ether solvents such as ether, di-propyl ether, petronium ether and methyl-t-butyl ether; Ketone solvents such as propanone, butanone, pentanone, hexanone and heptanone; And organic solvents such as methylene chloride, trifluoro isopropane, and carbon chloride.

Biodegradable polymers include cardiovascular materials such as stents, surgical sutures, tissue regeneration supports, bio-nanofibers, hydrogels, and bio-sponges; Dental materials such as pins, screws, screws, rods, implants; Or nerve / orthopedic / plastic surgery implants such as pins, screws, screws, supports for tissue regeneration, rods, and fillers; Or the like of the present invention serves as a base or matrix in the coating layer. That is, iodine or xenon is a structure in which a biodegradable polymer exists as a matrix. When the biodegradable polymer is decomposed, the iodine present in the part is also eliminated and discharged to the outside of the biodegradable polymer. When the biodegradable polymer is completely decomposed, the iodine and the like may be completely discharged to the outside of the body and the radiopacity may disappear.

Either the iodine source or the xenon source may be used, or the iodine source and the xenon source may be used together. The total content of iodine and xenon may be 0.01 to 95% by weight based on the total weight of the composition. When the content is less than 0.01% by weight, the radiopaque property may not be exhibited, and when it is more than 95% by weight, iodine may not be completely dissolved and precipitation may occur.

The radiopaque marker composition for bioabsorption of this aspect can be prepared by the following method.

First, the biodegradable polymer is weighed into the solvent. At this time, stirring is continuously performed to completely dissolve the biodegradable polymer.

Examples of the solvent include water; Alcohols such as methanol, ethanol, propanol, butanol, pentanol, heptanol, hexanol, octanol, nonanol, decanol; Aldehydes such as ammonia, dimethylsulfoxide, dimethylformamide, acetonitrile, tetrahydrofuran, formaldehyde, glutaraldehyde and acetaldehyde; Alkane solvents such as dioxane, chloroform, heptane, hexane, pentane, octane, nonane and decane; Benzene cyclic solvents such as benzene, toluene and xylene; Ether solvents such as ether, di-propyl ether, petronium ether and methyl-t-butyl ether; Ketone solvents such as propanone, butanone, pentanone, hexanone and heptanone; And at least one selected from the group consisting of common organic solvents such as methylene chloride, trifluoro isopropane, and carbon chloride can be used.

Examples of the biodegradable polymer include poly-L-lactide, poly-D-lactide, poly-D, L-lactide, polyglycolide, polycaprolactone, poly- Poly-D-lactide-co-glycolide, poly-D, L-lactide-co-glycolide, Polylactide-co-caprolactone, polylactic acid-co-caprolactone, polydioxanone, polytrimethylene carbonate, polyglycolide-co-dioxanone, polyamide ester, , Polyorthoesters, polymaleic acid, polyphosphazenes, polyanhydrides, polysevae corn hydrate, polyhydroxyalkanoates, polyhydroxybutyrates, polycyanoacrylates, polydodamine, cellulose, cellulose Acetate butyrate, cellulose triacetate, and their co- It can be used at least one polymer selected from the group consisting of a polymer.

The biodegradable polymer may be used in an amount of 0.01 to 90% by weight based on the total weight of the final composition. When the content of the biodegradable polymer is less than 0.01% by weight, the polymer coating layer and the matrix may not be formed. When the content of the biodegradable polymer is more than 90% by weight, the viscosity may become too high.

As the biodegradable polymer, those having a molecular weight of 1,000 to 3,000,000 can be used.

Next, the solution may be added with iodine, a compound containing iodine, a compound containing xenon and xenon, or a combination thereof, followed by stirring and dissolving.

Examples of the iodine-containing iodine compound include hydrogen iodide, sodium iodide, potassium iodide, methyl iodide, cesium iodide, potassium iodate, sodium periodate, calcium iodide, copper iodide, povidone iodide or a combination thereof.

As the xenon-containing xenon compounds, it is possible to use xenon difluorinated, xenon fluorinated, xenon fluorinated xenon, or a combination thereof.

Any one of the iodine source and the xenon source can be used, and the iodine source and the xenon source can be used together. The total content of iodine and xenon may be 0.01 to 95% by weight based on the total weight of the composition. When the content is less than 0.01% by weight, the radiopaque property may not be exhibited, and when it is more than 95% by weight, iodine may not be completely dissolved and precipitation may occur.

Another aspect of the present invention may be a surgical article comprising the bioabsorbable radiopaque marker composition. There are a variety of surgical articles to which the radiopaque marker composition for bioabsorption can be applied, and any article that exists in the human body after surgery can be applied.

Specifically, the surgical article includes a cardiovascular material such as a stent, a surgical suture, a tissue regeneration support, a bio-nanofiber, a hydrogel, and a bio-sponge; Dental materials such as pins, screws, screws, rods, implants; Or nerve / orthopedic / plastic surgery implants such as pins, screws, screws, supports for tissue regeneration, rods, fillers, and the like.

A representative example of such a surgical article is a stent. The stent may be coated with a radiopaque marker composition for absorbing bio-absorbance, or the polymer material for a stent matrix itself may contain a radiopaque marker composition for bioabsorption. As a stent, a metal stent as well as a biodegradable polymer stent can be used. As a method of coating the stent with the radiopaque marker composition for bioabsorption, ultrasonic spraying, electrospinning, dipping or the like can be used. In the case of ultrasonic spray spraying, the radiopaque marker composition for bioabsorption can be more uniformly coated on the stent than the electrospinning or dipping method. When the stent containing the radiopaque marker composition for bioabsorption is present in the human body, the position of the stent in the human body can be grasped accurately by irradiating the radiation.

Another example is a surgical suture. That is, it is a surgical suture containing a radiopaque marker composition for bioabsorption. Surgical sutures containing the radiopaque marker composition for bioabsorption can be prepared using conventional spinning techniques. That is, the radiopaque marker composition for bioabsorption and the polymer material for a surgical suture matrix may be melted and then extruded. Thus, a suture containing the radiopaque marker composition for bioabsorption can be produced on the surgical suture itself.

Another example is a scaffold. That is, a scaffold containing a radiopaque marker composition for bioabsorption. The scaffold containing the bioabsorbable radiopaque marker composition can be produced according to a conventional scaffold manufacturing method. Specifically, a conventional scaffold particle producing material such as a radiopaque marker composition for bioabsorption, ice particles for forming scaffold pores, sodium carbonate or sodium hydrogen carbonate, a solvent and a polymer substance are mixed, and then the mixture is added to a mold And then compressing it.

Another example is a surgical adhesive. That is, it is a surgical adhesive containing a radiopaque marker composition for bioabsorption. The surgical adhesive containing the radiopaque marker composition for bioabsorption can be prepared according to a conventional adhesive manufacturing process. Specifically, the radiation-impermeable marker composition for bioabsorption and the polymer substance are dissolved in a common solvent, whereby a surgical adhesive containing the marker composition can be produced.

Another example is a polymer screw. A polymer screw coated with a radiopaque marker composition for bioabsorption, or a polymeric screw containing a bioabsorbable radiopaque marker composition. As a method of coating the polymer composition with the marker composition, an ultrasonic spraying method, an electrospinning method or a dipping method may be used. The polymer screw containing the marker composition can be prepared by mixing a radioactive impermeable marker composition for bioabsorption with a polymer material and then subjecting it to a conventional injection molding process.

Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples. However, the present invention is not limited to the embodiments.

≪ Example 1 >

4 g of poly-L-lactide as a biodegradable polymer and 1 g of solid iodine were added to 95 g of tetrahydrofuran as a solvent, followed by stirring for 1 hour to dissolve the mixture to prepare a marker composition.

Separately, 5 g of poly L-lactic acid was added to and dissolved in 95 g of tetrahydrofuran, and 5 g of sirolimus was dissolved therein to prepare a drug release coating solution.

Next, in order to remove the substance adhering to the surface of the metal stent, it was washed with a mixed solvent of ethanol and distilled water for 1 hour using an ultrasonic washing machine, and dried in a hot air drier at 50 ° C for 24 hours.

Next, the prepared marker composition was coated on the stent by ultrasonic spraying. Specifically, an ultrasonic spraying device (Sonotech, MedicoatPSI) was used, the voltage of the ultrasonic vibrator was adjusted to 0.9 mV, the spray flow rate to 0.03 ml / min, and the coating was performed for 40 seconds. The rotation speed of the stent was 50 RPM and the moving speed was 0.03 cm / sec.

Next, the stent coated with the marker composition was vacuum-dried in a vacuum dryer at 40 캜 for 24 hours. The thickness of the marker composition coating layer was 2 탆.

Next, the drug release coating solution was coated on the stent coated with the marker composition using an ultrasonic spraying apparatus. The coating was carried out for 1 minute and 30 seconds under the same conditions as those for coating the marker composition. The thickness of the drug release coating layer was 6 μm.

Thus, a metal stent having a dual coating layer structure was prepared.

≪ Example 2 >

5 g of polycaprolactone and 5 g of xanthone were added to 90 g of dimethyl sulfoxide as a solvent and dissolved while stirring for 1 hour to prepare a marker composition.

Separately, 10 g of paclitaxel and 10 g of poly-carprolactone were dissolved in 80 g of tetrahydrofuran (THF) as a solvent to prepare a drug release coating solution.

Next, in order to remove the substance adhering to the surface of the metal stent, it was washed with a mixed solvent of ethanol and distilled water for 1 hour using an ultrasonic washing machine, and dried in a hot air drier at 50 ° C for 24 hours.

Next, a drug release coating layer was formed on the metal stent with a drug release coating solution by controlling the spinning speed to 0.5 ml / min, the spinning distance to 10 cm, and the voltage to 1000 mV using electrospinning for 10 minutes. Coating was carried out for 2 minutes. The thickness of the drug release coating layer was 7 [mu] m.

Next, the ultrasonic spray method was used to adjust the voltage of the ultrasonic vibrator to 0.5 mV and the spray flow rate to 0.05 ml / min on the stent coated with the drug release coating solution, and the coating was performed for 30 seconds. The stent was rotated at a rate of 60 RPM and a moving speed of 0.05 cm / sec to coat the marker composition for 1 minute. The thickness of the marker coating layer was 3 탆.

Thus, a metal stent having a dual coating layer structure was prepared.

≪ Example 3 >

36 g of poly (lactide-co-glycolide) and 4 g of iodine were added to 60 g of chloroform as a solvent and dissolved with stirring for 1 hour to prepare a marker composition .

Next, to 0.7 g of the marker composition, 0.3 g of ice particles having a size of 1 to 10 μm, and 9 g of polylactide-co-glycolide were dissolved in 10 g of chloroform to prepare a 2 cm diameter, 2 mm high To prepare a scaffold.

<Example 4>

34 g of polylactide and 6 g of xanthone were added to 60 g of chloroform as a solvent, and dissolved with stirring for 1 hour to prepare a marker composition.

Next, the marker composition was impregnated with an orthopedic polymer screw for 3 minutes, and then dried in air to prepare a polymer screw coated with the marker composition.

&Lt; Example 5 >

18 g of 70 g of polydioxanone and 12 g of iodine were added to acetonitrile as a solvent and dissolved while stirring for 1 hour to prepare a marker composition.

Next, 50 g of the prepared marker composition was adjusted to a screw speed of 70 rpm, a chamber temperature of 200 ° C, and a voltage of 1100 mV to prepare a surgical suture through electrospinning.

&Lt; Example 6 >

32 g of polylactide and 8 g of iodide were added to 60 g of chloroform as a solvent, and dissolved while stirring for 1 hour to prepare a marker composition.

Next, the above-mentioned marker composition was extruded through an extruder having an extrusion rotational speed of 200 rpm and a chamber temperature of 220 degrees, and then a pattern was formed using a Femto second laser having a voltage controlled at 1350 mV to prepare a biodegradable polymeric stent.

&Lt; Example 7 >

18 g of polythioacrylate and 2 g of iodine were added to 80 g of dimethylsulfoxide solvent and stirred for 1 hour to prepare a surgical adhesive containing the marker composition.

&Lt; Comparative Example 1 &

20 g of poly L-lactide was added to 80 g of tetrahydrofuran and dissolved while stirring. The above-mentioned marker composition was extruded through an extruder having an extrusion rotational speed of 250 rpm and a chamber temperature of 210 ° C A biodegradable polymer stent was fabricated by patterning using a Femto second-order laser with a voltage of 1300 mV

Next, a circular groove having a diameter of 2 mm was formed at the distal end of the biodegradable polymer stent, and 1 g of platinum was applied under pressure.

&Lt; Comparative Example 2 &

19 g of polylactide and 1 g of sirolimus were added to 80 g of dimethyl sulfoxide as a solvent and dissolved while stirring to prepare a drug release coating solution.

Next, the drug release coating solution was coated by ultrasonic spraying on a metal stent. Specifically, the voltage of the ultrasonic vibrator was adjusted to 0.9 mV, the spray flow rate to 0.03 ml / min, and the coating was performed for 40 seconds. The rotation speed of the stent was 50 RPM and the moving speed was 0.03 cm / sec.

Next, a 3 mm circular groove was drilled at the end of the metal stent, and then 2 g of gold was pressurized and mounted.

<Evaluation>

Each composition prepared according to Examples and Comparative Examples was dropped on a plastic substrate, and X-ray opacity was measured by X-ray imaging using an X-ray measuring apparatus (LISTEM, PROGEN-R diagnostic X-ray apparatus). The impermeability was calculated as follows.

(Impermeability) (%) = (impermeable area measured on the photograph) / (actual area) x 100

The results of the impermeability calculation are shown in Table 1. Immediately after manufacture (labeled "initial") and again after 12 months. The following criteria were used for the classification.

Class 1: Impermeability 80% or more,

Class 2: Impermeability less than 80%

Class 3: Impermeability less than 50%

4 Grade: Less than 20% impermeability,

Class 5: Not distinguishable.

Impermeability grade (% impermeability) Early After 12 months Example 1 1st grade (97%) 1 rating (96%) Example 2 1 rating (93%) 1 rating (90%) Example 3 1 rating (85%) 2 ratings (75%) Example 4 2 ratings (77%) 2 ratings (75%) Example 5 1 rating (85%) 2 ratings (78%) Example 6 1 rating (92%) 1 rating (88%) Example 7 2 ratings (70%) 2 ratings (68%) Example 8 1 rating (84%) 2 ratings (78%) Example 9 1 rating (87%) 2 ratings (75%) Example 10 2 ratings (72%) 2 ratings (45%) Example 11 1 rating (94%) 1 rating (91%) Comparative Example 1 4 stars (15%) 5th grade (not distinguishable) Comparative Example 2 4 ratings (12%) 4 stars (10%)

Referring to Table 1, in comparison with the initial measurement result and the measurement result after 12 months, although the impermeability was slightly decreased in the Examples, the impermeability of the first or second grade was still maintained. However, in the case of the comparative example, low impermeability such as that measured from the initial measurement result to the fourth grade is shown.

Claims (15)

A radiopaque marker composition for bioabsorption comprising xenon. The method according to claim 1,
Wherein the xenon source supplying the xenon comprises at least one selected from the group consisting of atropylated xenon, xylofluorinated xenon and xylofluorinated xenon. The method according to claim 1,
A biodegradable radiopaque marker composition further comprising a biodegradable polymer. The method of claim 3,
Wherein the biodegradable polymer is dissolved in a hydrophilic solvent. 5. The method of claim 4,
The solvent is selected from the group consisting of water; Alcohols including methanol, ethanol, propanol, butanol, pentanol, heptanol, hexanol, octanol, nonanol and decanol; Aldehydes including ammonia, dimethylsulfoxide, dimethylformamide, acetonitrile, tetrahydrofuran, formaldehyde, glutaraldehyde and acetaldehyde; Alkanes including dioxane, chloroform, heptane, hexane, pentane, octane, nonane and decane; Benzene ring-type solvents including benzene, toluene and xylene; Ethers, including ethers, di-propyl ethers, petronium ethers and methyl-t-butyl ethers; Ketones including propanone, butanone, pentanone, hexanone and heptanone; Methylene chloride, fluoroisopropane, and carbon tetrachloride. The radiopaque marker composition according to claim 1, The method of claim 3,
Wherein the biodegradable polymer is selected from the group consisting of poly-L-lactide, poly-D-lactide, poly-D, L-lactide, polyglycolide, polycaprolactone, poly-L-lactide-co- L-lactide-co-glycolide, poly-L-lactide-co-glycolide, poly-D- Caprolactone, polylactide-co-caprolactone, polyglacolide-co-caprolactone, polydioxanone, polytrimethylene carbonate, polyglycolide-co-dioxanone, polyamide ester, The present invention relates to a method for producing a polyhydroxyalkanoate having a hydrophilic functional group such as a polypeptide, a polyorthoester system, a polymaleic acid, a polyphosphazene, a polyanhydride, a polyseva cyanide hydride, a polyhydroxyalkanoate, a polyhydroxybutyrate, a polycyanoacrylate, Cellulose acetate butyrate, cellulose triacetate and their Wherein the at least one radioisotope marker composition comprises at least one selected from the group consisting of a radioisotope and a copolymer. The method of claim 3,
Wherein the content of the biodegradable polymer is 0.01 to 90% by weight based on the total weight of the composition. The method according to claim 1,
Wherein the total content of the xenon is 0.01 to 95% by weight based on the total weight of the composition. A stent coated with the radiopaque marker composition for bioabsorption according to claim 1. A polymeric screw coated with the radiopaque marker composition for bioabsorption according to claim 1. A biodegradable polymeric stent comprising the radiopaque marker composition for bioabsorption according to claim 1. A scaffold containing the bioabsorbable radiopaque marker composition of claim 1. A surgical suture comprising the bioabsorbable radiopaque marker composition of claim 1. A surgical article comprising the radiopaque marker composition for bioabsorption according to claim 1. The surgical article according to claim 14, wherein the surgical article is at least one selected from the group consisting of a tissue regeneration support, a bio-nanofiber, a hydrogel, a bio-sponge, a pin, a screw, a screw, a rod, a filler, Included surgical items.