KR101667328B1 - Hydrogel particle and composite embolic material - Google Patents
Hydrogel particle and composite embolic material Download PDFInfo
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Abstract
At least one biodegradable polymer of at least one of gelatin and chitosan and at least one C 18 -C 26 aliphatic hydrocarbon derivative of an alkylamine and alkyl amide, wherein the methylene (CH 2 ) of a C 18 -C 26 aliphatic hydrocarbon, of the CH stretching vibration (stretching vibration) 2850 cm -1 peak to 3000 cm - the composite embolic materials containing them with hydrogel particles having the FT-IR spectrum that appears in the wave number range of 1 it is provided.
Description
The invention is directed to the hydrogel particles and complex embolization materials used in embolization.
Liver tissue is supplied by oxygen and nutrients by two blood vessels. One is the portal vein, which is the portal vein, and the other is the hepatic artery, which comes directly from the aorta. Normal liver tissue is mainly in the context, and tumor tissue is supplied mainly in the hepatic artery. Therefore, only the hepatic artery supplying the tumor is selected, and when the cancer drug is administered and the blood vessel is blocked after the administration of the anticancer drug, only the tumor can be selectively necrotized without significantly damaging the normal liver tissue.
Transarterial chemoembolization is a treatment for hepatocellular carcinoma (hepatocellular carcinoma) by administering anticancer drugs to find hepatic artery supplying hepatocellular carcinoma.
Through the femoral artery located in the groin (inguinal), a thin tube of about 2 ~ 3 mm called a catheter is inserted to approach the hepatic artery. When the catheter is inserted into the hepatic artery, an angiographic contrast agent is injected into the hepatic artery to obtain information on the position, size and blood supply of the tumor. When the treatment is decided, a thin tube of about 1 mm in thickness is used to find the hepatic artery to the hepatic tumor and to put an anticancer agent and an embolization substance into it.
Average Typical examples of embolic materials used in embolization liver chemistry, may be mentioned lipiodol ® (lipiodol ®) and gelpom ® (gelfoam ®).
Lipiodol ® is an iodinated ethyl ester of poppy seed oil fatty acids derived from, when the anticancer agent and the mixed injection is selectively deposited in the liver tumor. Lipiodol ® is a fat-soluble iodine based contrast media, it may serve as the embolic material having embolic effect of microvessels.
Excessive use of iodine contrast agents may cause side effects such as nausea, vomiting, urticaria, itching, hypotensive shock, respiratory arrest, cardiac arrest, and convulsions. Lipiodol ® it can serve as embolic materials. However, since the fat-soluble iodine based contrast agents over-use of lipiodol ® can cause side effects such as nausea, vomiting, urticaria, itching, hypotensive shock, respiratory arrest, cardiac arrest, convulsions.
Gelpom ® is a block in the nutrients supplied to the liver tumors by promoting thrombus formation or blocking the flow of blood, and the main component is composed of proteins with excellent safety embolic material in the hepatic artery.
Gelpom ® is composed of protein, so does the safety is not excellent, but the selective deposition in the liver tumors did not function as a contrast agent, in the case of using only gelpom ® alone, or artery or vein connected to other organs such as the brain, not the hepatic artery in Which may result in the formation of blood clots or block blood flow.
Also, for example, even when subjected to liver chemical embolization of chemotherapy and lipiodol ® primary injection after gelpom ® as a secondary injection which, as in the case of using only gelpom ® alone, or the brain and non-hepatic Side effects may occur in the arteries or veins connected to the same organs, such as forming blood clots or blocking blood flow.
The present invention aims to provide a composite embolization material in which the side effects of the iodine contrast agent are minimized and at the same time, the selective thrombus formation and blood flow blocking function of the embolization substance are improved and the embolization gel particles for embolization used therefor.
The present invention has been made in view of the above problems, and it is an object of the present invention to provide an apparatus and method for controlling the same.
The hydrogel particles according to one embodiment of the invention include at least one biodegradable polymer of gelatin and chitosan and at least one C 18 -C 26 aliphatic hydrocarbon derivative of an alkylamine and alkyl amide.
Hydrogel particles in accordance with one embodiment of the invention, C 18 ~ C 26 aliphatic hydrocarbon group of methylene (CH 2) a CH stretching vibration (stretching vibration) 2850 cm -1 peak to 3000 cm - FT appears in the wave number range of from 1 -IR spectra.
Hydrogel particles in accordance with one embodiment of the invention is an iodide C 18 ~ C 26 average absorption of the fatty acid ester exceeds 50% by weight, based on the amount of the iodide C 18 ~ C 26 fatty acid esters.
Hydrogel particles in accordance with one embodiment of the invention, followed by the addition of a phosphate buffered saline (PBS) centrifuged was then measured after removing the supernatant the iodide C 18 ~ C 26 average residual content of the iodide C 18 fatty acid ester ~ C 26 is in excess of 25% by weight, based on the addition amount of the fatty acid ester.
The complex embolization material according to an embodiment of the present invention includes the above-mentioned hydrogel particles and an iodinated C 18 -C 26 fatty acid ester.
The C 18 -C 26 aliphatic hydrocarbon derivative may be a C 18 -C 26 n-alkyl derivative.
The alkylamine may be a C 18 -C 26 n-alkylamine. The C 18 -C 26 n-alkylamine may be octadecylamine.
The alkyl amide may be a C 18 -C 26 n-alkyl amide. The C 18 -C 26 n-alkyl amide may be octadecane amide.
The iodinated C 18 -C 26 fatty acid ester may be ethyl monoiodostearate.
The iodide C 18 ~ C 26 may be an average water absorption of the fatty acid ester it exceeds 70% by weight, based on the amount of the iodide C 18 ~ C 26 fatty acid esters.
The iodide C 18 ~ C 26 is the average value of the average absorption of the fatty acid ester can be less than the iodide C 18 ~ C 26 exceeds 85% by weight, based on the amount of fatty acid ester to 88% by weight.
The average residual content of the phosphoric acid was added to buffered saline (PBS) centrifugation was separated with the iodide, measured after removal of the supernatants C 18 ~ C 26 fatty acid esters are based on the amount of the iodide C 18 ~ C 26 fatty acid ester By weight to 35% by weight.
The added amount of was added to the phosphate-buffered saline (PBS) centrifugation was separated measured after removing the supernatant the iodide C 18 ~ C 26 average residual content of the average value of the iodide C 18 ~ C 26 fatty acid ester of a fatty acid ester To less than 77% by weight based on the total weight of the composition.
The details of other embodiments are included in the detailed description and drawings.
The hydrogel particles and the complex embolization agent according to an embodiment of the present invention can minimize the use of the iodine contrast agent, thereby reducing the side effects of the iodine contrast agent and preventing the formation of a thrombus selectively in the blood vessel, The accuracy of embolization can be increased.
The effects according to the present invention are not limited by the contents exemplified above, and more various effects are included in the specification.
1 is a photomicrograph of an
2 is a photomicrograph of an
3 is a photomicrograph of an
4 is a photomicrograph of an
5 is a photomicrograph of an experimental sample 5 according to an embodiment of the invention.
6 is a photomicrograph of an
7 and 8 are comparative plots of the experimental samples lipiodol ® absorbent hydrogel particles of the comparative sample with the hydrogel particles in accordance with one embodiment of the invention.
9 and 10 are experimental compound embolism lipiodol ® residual content comparison graph of the material sample and the comparative composite material sample embolization according to one embodiment of the invention.
Figure 11 is a graph comparing the amount of test compound lipiodol ® embolic material sample for lipiodol ® content of the comparison compound embolic material sample based on the analysis gas chromatography (GC).
12 to 14 for the gas content of the test compound lipiodol ® embolic material sample in accordance with one embodiment of the invention, chromatographic (GC) analysis results are graphs.
15 and 16 are gas chromatography for the content of the comparison compound lipiodol ® embolic material samples (GC) analysis result graphs are
17 is a graph of gas chromatography (GC) analysis results of a standard product.
18 to 20 are FT-IR spectra of the hydrogel particles of an experimental sample according to an embodiment of the present invention.
21 and 22 are FT-IR spectra of the hydrogel particles of the comparative sample.
BRIEF DESCRIPTION OF THE DRAWINGS The features and advantages of the present invention will become more apparent from the following detailed description taken in conjunction with the accompanying drawings, in which: FIG.
A "hydrogel particle" is a particle that can be used for embolization and can be swollen by water as a kind of embolization substance. The hydrogel particles may be sphere-shaped particles having a smooth spherical surface in order to prevent inflammation that may occur when they are in contact with the blood vessel wall for a long time after embolization. The size of the hydrogel particles is not particularly limited, but may be determined within a range of several μm to several hundreds of μm.
The term "composite embolization substance" means an embolus material in which two or more types of embolization materials are combined, or an embolus material in which one type of embolization material and one type of contrast agent are combined. The complex embolization material also includes a case where the function of the embolus substance and the function of the contrast agent function in a complex manner, such as when one kind of embolization substance has the function of the contrast agent.
A "biodegradable polymer" is a biomaterial that is gradually degraded in the body after transplantation and replaced with a regenerating autologous tissue. For example, the biodegradable polymer may be a natural polymeric compound, and the natural polymeric compound may be at least one of gelatin and chitosan, for example. The gelatin and the chitosan may be used alone as the biodegradable polymer, or a combination thereof, that is, a combination of the gelatin and the chitosan may be used as the biodegradable polymer.
The " C18 to C26 aliphatic hydrocarbon derivative" is a derivative of an aliphatic hydrocarbon having from 18 to 26 carbon atoms.
"C 18 -C 26 alkylamine" is an amine having alkyl having from 18 to 26 carbon atoms. "C 18 -C 26 alkyl amide" is an amide having alkyl having from 18 to 26 carbon atoms.
"C 18 -C 26 alkyl" refers to C 18 -C 26 n-alkyl and C 18 -C 26 iso-alkyl, which do not have side-chain carbon chains attached to the main carbon chain, or alkyl having a side chain carbon chain attached to the main carbon chain such as < RTI ID = 0.0 > sec-alkyl. < / RTI >"Amines" and "amides " include diamines and diamides, respectively.
An example of the C 18 to C 26 n-alkylamine is octadecyl amine.
An example of the C 18 to C 26 n-alkyl amide includes octadecyl amine.
The "iodinated C 18 -C 26 fatty acid ester" is a compound in which iodine is substituted for a fatty acid ester having an alkyl of 18 to 26 carbon atoms. Examples of the iodide C 18 ~ C 26 fatty acid esters there may be mentioned lipiodol ®, the lipiodol ® may be a mono-iodo ethyl stearate (ethyl monoiodostearate).
"Iodide C 18 ~ C 26 average absorption of the fatty acid ester" is an amount of a C 18 ~ C 26 fatty acid ester, measured after having added the iodide C 18 ~ C 26 fatty acid ester of a predetermined amount of the embolic material and centrifuging the mixture .
"Iodide C 18 ~ C 26 average residual content of the fatty acid ester" is measured after a mixture of phosphate buffered saline (PBS) with a predetermined amount of the embolic material are the iodide C 18 ~ C 26 fatty acid esters absorbed and centrifuging the mixture The residual content of one C 18 to C 26 fatty acid ester.
The hydrogel particles according to an embodiment of the present invention include the biodegradable polymer and a C 18 -C 26 aliphatic hydrocarbon derivative. The C 18 -C 26 aliphatic hydrocarbon derivative may be, for example, a C 18 -C 26 alkylamine and / or a C 18 -C 26 alkylamide. As used herein, "A and / or B" means "A, B or A and B".
The C 18 -C 26 alkylamine and the C 18 -C 26 alkylamide may each include a linker bonded to the biodegradable polymer, and the linker may have a chemical structure derived from a crosslinking agent.
For example, the crosslinking agent may be formaldehyde, glutaraldehyde, genipin, and the like.
For example, where the formaldehyde is used as a crosslinking agent, each of the C 18 -C 26 alkylamine and the C 18 -C 26 alkylamide may comprise a methylene bridge bonded to the biodegradable polymer . At this time, the methylene bridge can function as a linker.
The methylene bridge may be derived from the methylene of methylene glycol (HOCH 2 OH) produced by the reaction of formaldehyde with water, and may be a dehydration condensation reaction of the biodegradable polymer, the C 18 -C 26 aliphatic hydrocarbon derivative and methylene glycol Each of the C 18 -C 26 alkylamine and the C 18 -C 26 alkyl amide may comprise the methylene bridge as a linker.
As an example, the methylene bridge may link the nitrogen atom (N) of the gelatin with the nitrogen atom (N) of the C 18 -C 26 alkylamine, or the nitrogen atom (N) of the gelatin and the C 18 -C 26 The nitrogen atom (N) of the alkyl amide can be connected.
As another example, the methylene bridge may link the nitrogen atom (N) of the chitosan with the nitrogen atom (N) of the C 18 -C 26 alkylamine, or the nitrogen atom (N) of the chitosan and the C 18 -C Lt; RTI ID = 0.0 > (N) < / RTI >
For example, where the glutaraldehyde is used as the crosslinking agent, each of the C 18 -C 26 alkylamine and the C 18 -C 26 alkylamide may comprise a Shiff base bound to the biodegradable polymer have. At this time, the Schiff base may function as a linker.
By the dehydration condensation reaction of the biodegradable polymer, the C 18 -C 26 aliphatic hydrocarbon derivative and the methylene glycol, the C 18 -C 26 alkylamine and the C 18 -C 26 alkylamide each contain the Schiff base as a linker .
As an example, the Schiff base may link one nitrogen atom (N) of the gelatin and the chitosan to the nitrogen atom (N) of the C 18 -C 26 alkylamine, or one nitrogen atom of the gelatin and the chitosan (N) and the nitrogen atom (N) of the C 18 -C 26 alkylamide.
For example, where the Jenin fins are used as the crosslinking agent, each of the C 18 -C 26 alkylamine and the C 18 -C 26 alkylamide may include a linker represented by the following formula (1).
In the following formula (1), the nitrogen atom (N) of the heterocyclic amine may be one nitrogen atom (N) of the gelatin and the chitosan, and the nitrogen atom (N) of the amine adjacent to the carbonyl group the may be a C 18 ~ C 26 alkyl amine and a C 18 ~ C 26 alkyl, a nitrogen atom (N) of the amide.
≪ Formula (1) >
The C 18 -C 26 aliphatic hydrocarbon derivative can be uniformly mixed with the biodegradable polymer within the range of C 18 -C 26 , and can produce many bubbles during whipping. As can be seen from the following experimental examples, when hexadecylamine was used as the C 18 -C 26 aliphatic hydrocarbon derivative, mixing was not performed well, and bubbles could not be visually confirmed even when whipped. This will be described more specifically in the following experimental examples.
The composite embolization material according to an embodiment of the present invention includes the hydrogel particles and an iodinated fatty acid ester. It is presumed that the iodinated fatty acid ester is bonded through the hydrophilic interaction with the aliphatic hydrocarbon derivative.
That is, since the complex embolization substance according to an embodiment of the present invention has a hydrophobic interaction between the carbon chain of the C 18 -C 26 aliphatic hydrocarbon derivative and the carbon chain of the iodinated fatty acid ester, .
For example, the iodinated fatty acid ester may be an iodinated fatty acid ester in which the carbon chain is C 18 to C 26 n-alkyl. The carbon chain of the C 18 -C 26 aliphatic hydrocarbon derivative may include n-alkyl to increase the hydrophobic interaction between the alkyls. For example, the C 18 -C 26 alkylamine may be a C 18 -C 26 n-alkylamine, and the C 18 -C 26 alkylamide may be a C 18 -C 26 n-alkylamide.
From the experimental examples described below, it can be confirmed that the hydrogel particles and the complex embolization substance according to one embodiment of the present invention each have an excellent absorption or binding force for the iodinated C 18 -C 26 fatty acid ester.
Hereinafter, the hydrated gel particles and the complex embolization substance according to one embodiment of the present invention will be described in more detail through experimental examples using experimental samples and comparative samples.
<Production example of
Gelatin was dissolved in water at 60 ° C to prepare a 6% gelatin aqueous solution. Octadecylamine was dissolved in ethanol to prepare a 2.5% octadecylamine ethanol solution.
100 mL of a 6% gelatin aqueous solution and 10 mL of a 2.5% octadecylamine ethanol solution were taken and mixed, followed by stirring until uniformly mixed. Then, 11.75 mL of a 3% formaldehyde aqueous solution was added to the resultant, and stirred at 2000 rpm for 15 minutes using a foam maker to prepare an
≪ Production example of
Gelatin was dissolved in water at 60 ° C to prepare a 6% gelatin aqueous solution. Octadecylamine was dissolved in ethanol to prepare a 5% octadecylamine ethanol solution.
100 mL of a 6% gelatin aqueous solution and 10 mL of a 5% octadecylamine ethanol solution were taken and mixed, followed by stirring until uniformly mixed. Then, 11.75 mL of glutaraldehyde was added to the resultant of the stirring, and stirred at 2000 rpm for 15 minutes using a foam maker to prepare an
<Production example of
The chitosan was dissolved in water at 60 ° C to prepare a 6% aqueous chitosan solution. Octadecylamine was dissolved in ethanol to prepare a 5% octadecylamine ethanol solution.
100 mL of a 6% aqueous chitosan solution and 10 mL of a 5% octadecylamine ethanol solution were taken and mixed, followed by stirring until uniformly mixed. Then, 11.75 mL of a 3% formaldehyde aqueous solution was added to the resultant, and stirred at 2000 rpm for 15 minutes using a foam maker to prepare an
<Production example of
Chitosan and gelatin were mixed at a mass ratio of 3: 7 to prepare a chitosan-gelatin mixture. The chitosan-gelatin mixture was dissolved in water at 60 ° C to prepare a 6% aqueous chitosan-gelatin mixture solution. Octadecylamine was dissolved in ethanol to prepare a 5% octadecylamine ethanol solution.
100 mL of the 6% chitosan-gelatin mixture aqueous solution and 10 mL of the 5% octadecylamine ethanol solution were taken and mixed, and the mixture was stirred until uniformly mixed. Then, 11.75 mL of a 3% formaldehyde aqueous solution was added to the resultant, and the mixture was stirred at 2000 rpm for 15 minutes using a foam maker.
<Production example of test sample 5>
Chitosan and gelatin were mixed at a mass ratio of 7: 3 to prepare a chitosan-gelatin mixture. The chitosan-gelatin mixture was dissolved in water at 60 ° C to prepare a 6% aqueous chitosan-gelatin mixture solution. Octadecylamine was dissolved in ethanol to prepare a 5% octadecylamine ethanol solution.
100 mL of the 6% chitosan-gelatin mixture aqueous solution and 10 mL of the 5% octadecylamine ethanol solution were taken and mixed, and the mixture was stirred until uniformly mixed. Then, 11.75 mL of a 3% formaldehyde aqueous solution was added to the resultant, and the mixture was stirred at 2000 rpm for 15 minutes using a foam maker.
<Production example of
Gelatin was dissolved in water at 60 ° C to prepare a 6% gelatin aqueous solution. Octadecylamine was dissolved in ethanol to prepare a 5.0% octadecylamine ethanol solution.
100 mL of a 6% gelatin aqueous solution and 10 mL of a 5.0% octadecylamine ethanol solution were taken and mixed, followed by stirring until uniformly mixed. Then, 11.75 mL of a 3% formaldehyde aqueous solution was added to the resultant, and the mixture was stirred at 2000 rpm for 15 minutes using a foam maker.
<Production example of
Gelatin was dissolved in water at 60 ° C to prepare a 6% gelatin aqueous solution. Hexadecylamine was dissolved in ethanol to prepare a 5% hexadecylamine ethanol solution.
100 mL of a 6% gelatin aqueous solution and 10 mL of a 5% hexadecylamine ethanol solution were taken and mixed, followed by stirring until uniformly mixed. Then, 11.75 mL of a 3% formaldehyde aqueous solution was added to the resultant, and the mixture was stirred at 2000 rpm for 15 minutes using a foam maker to prepare a
<Production example of
The chitosan was dissolved in water at 60 ° C to prepare a 6% aqueous chitosan solution. Hexadecylamine was dissolved in ethanol to prepare a 5% hexadecylamine ethanol solution.
100 mL of a 6% aqueous solution of chitosan and 10 mL of a 5% hexadecylamine ethanol solution were taken, mixed, and stirred until uniformly mixed. Then, 11.75 mL of 3% formaldehyde aqueous solution was added to the resultant, and the mixture was stirred at 2000 rpm for 15 minutes using a foam maker to prepare a
≪ Experimental Example 1: Characteristic comparison >
The degree of foaming of the
1 is a photomicrograph of an
Referring to FIGS. 1 to 6 and Table 1, it can be seen that the
It was confirmed that it was difficult to prepare the porous hydrogel particles from Experimental Example 1 in which
<Production example of
Gelatin was dissolved in water at 60 ° C to prepare a 6% gelatin aqueous solution. Octadecylamine was dissolved in ethanol to prepare a 0.5% octadecylamine ethanol solution.
100 mL of a 6% gelatin aqueous solution and 10 mL of a 0.5% octadecylamine ethanol solution were taken and mixed, followed by stirring until uniformly mixed. Then, 11.75 mL of a 3% formaldehyde aqueous solution was added to the resultant, and the mixture was stirred at 2000 rpm for 15 minutes using a foam maker.
The resultant mixture was naturally dried at room temperature, and the natural dried product was finely crushed. The hydrogel particles having a size of 560 쨉 m to 710 쨉 m were selected to prepare
≪ Production example of
Octadecylamine was dissolved in ethanol to prepare a 1.0% octadecylamine ethanol solution. Then, 100 mL of a 6% gelatin aqueous solution and 10 mL of a 1.0% octadecylamine ethanol solution were taken and mixed. Then, the mixture was stirred until homogeneous mixing , An
<Production example of
Octadecylamine was dissolved in ethanol to prepare a 2.0% octadecylamine ethanol solution. Then, 100 mL of a 6% gelatin aqueous solution and 10 mL of a 2.0% octadecylamine ethanol solution were taken and mixed. Then, the mixture was stirred until uniformly mixed , An
<Production example of
Octadecylamine was dissolved in ethanol to prepare a 2.5% octadecylamine ethanol solution. Then, 100 mL of a 6% gelatin aqueous solution and 10 mL of a 2.5% octadecylamine ethanol solution were taken and mixed. Then, the mixture was stirred until uniformly mixed , An
<Production example of
Octadecylamine was dissolved in ethanol to prepare a 5.0% octadecylamine ethanol solution. Then, 100 mL of a 6% gelatin aqueous solution and 10 mL of 5.0% octadecylamine ethanol solution were taken and mixed. Then, the mixture was stirred until uniformly mixed , An
≪ Production example of
Octadecylamine was dissolved in ethanol to prepare a 10.0% octadecylamine ethanol solution. Then, 100 mL of a 6% gelatin aqueous solution and 10 mL of 10.0% octadecylamine ethanol solution were taken and mixed. Then, the mixture was stirred until uniformly mixed , An
≪ Production example of
Octadecanamide was dissolved in ethanol to prepare a 2.5% octadecanamide ethanol solution. Then, 100 mL of a 6% gelatin aqueous solution and 10 mL of a 2.5% octadecanamide ethanol solution were taken and mixed. Then, the mixture was stirred until homogeneous mixing , An
<Production example of
Gelatin was dissolved in water at 60 ° C to prepare a 6% gelatin aqueous solution. To 100 mL of 6% gelatin aqueous solution was added 11.75 mL of 3% formaldehyde aqueous solution and stirred at 2000 rpm for 15 minutes using a foam maker.
The resultant agitated product was naturally dried at room temperature, the naturally dried product was finely crushed, and hydrogel particles having a size of 560 쨉 m to 710 쨉 m were selected.
<Production example of
As the embolization gelatin Prime Material curry was used for gel ® (Cali-Gel ®). Cali-Gel ® was purchased from Embo transgenic (EMBOGENIC) four (社).
<Experimental Example 2: Comparative uptake of lipiodol ®>
Using a
50 mg each of the
After the
After centrifugation at 4000 rpm for 1 min, the supernatant was removed and the mass was measured. It was converted to lipiodol ® mass in the measure. The above procedure was repeated three times.
7 is a graph comparing
Addition amount (g)
Mass conversion value (g)
On the other hand, Figure 7 and Referring to Table 2, even considering the experimental error detection hydrogel particles of the
The
7 and Table 2, unlike the
The average absorbed amount of Lipiodol ( R) in
<Experiment 3: Comparative uptake of lipiodol ®>
Fig. 8 is a graph showing a comparison of absorption of lipidol with the hydrated gel particles of
Addition amount (g)
Mass conversion value (g)
Hydrogel particles of Figure 8 and Table Referring to Figure 3, compare hydrogel particles of the
In addition, the hydrogel particles of the
<Experimental Example 4: Comparison of the residual content of lipiodol ®>
In order to simulate the actual embolization, 5 mL of phosphate buffered saline (PBS) was added to each of the tubes of the
After centrifugation at 4000 rpm for 1 minute, the supernatant was removed, and the mass was measured. It was converted to lipiodol ® mass in the measure. The above procedure was repeated three times.
Figure 9 is an
Addition amount (g)
Mass conversion value (g)
9 and referring to Table 4, even considering the experimental error detection hydrogel particles of the
The experimental hydrogel particles of the
9 and Table 4, the
Haebomyeon translates to a numerical value, the experiment sample average of the mean content of the self-esteem of 7 to 12 lipiodol ® was the average of the average uptake of lipiodol ® of a 72.4% by weight, 8 to 12 test samples is 76.3% by weight. And from this,
Experimental Example 5: Comparison of Residual Content of Lipiodol 占 ?
Figure 10 is a comparison graph of lipiodol ® absorbent hydrogel particles in the experimental sample and the
Addition amount (g)
Mass conversion value (g)
With reference to Table 5 and FIG. 10, in consideration of the experimental error, the hydrogel particles of
In addition, the hydrogel particles of the
Experimental Example 6: GC / MS >
50 mg each of the
After the
* Table 5 provides a comparison of lipiodol ® content of experimental sample embolic materials for lipiodol ® content of the comparison compound embolic material sample.
Referring to Table 6 and Figure 11, the test composite sample embolic materials can see this amount of water absorption of 150% of lipiodol ® plenty compared to comparative compound embolic material sample.
The GC analysis results of FIGS. 12 to 17 are summarized in Table 7 below. 12 is a gas chromatograph of the experimental composite samples embolic materials Photography (GC) is an analysis result graph including a
13 is a gas chromatogram of the experimental sample composite embolic materials Photography (GC) is an analysis result graph containing hydrogel particles, and lipiodol ® of
14 is a test sample of 12 experimental composite embolic material sample containing the hydrogel particles and lipiodol ® gas chromatography (GC) analysis graph.
Figure 15 is a comparison of three samples of the comparative compound embolic material sample containing the hydrogel particles and lipiodol ® gas chromatography (GC) analysis graph.
Figure 16 is a
17 is a graph of gas chromatography (GC) analysis results of a standard product.
Table 8 below is a mass spectrometry (MS) result table. Referring to Table 8 below, it can be confirmed that ethyl stearate was detected near 27.0 minutes, and it can be confirmed that 98% of the concordance is observed. Figure 11 is a comparison of the relative content of gas chromatography lipiodol ® 27.0 minutes based on the peak area units and based on a (GC) analysis of the 12 to 16.
<Experimental Example 7: FT-IR spectrum>
The chemical structure of the hydrogel particles of the test sample and the chemical structure of the hydrogel particles of the comparative sample were compared and analyzed using the
18 is an FT-IR spectrum of the hydrogel particles of the
19 is an FT-IR spectrum of the hydrogel particles of the
20 is an FT-IR spectrum of the hydrogel particles of the
21 is FT-IR spectra of the hydrated gel particles of the
22 is FT-IR spectra of the hydrated gel particles of
18 to 22, the hydrogel particles of
About 2850 cm -1 to about 3000 cm - CH stretching vibrations in the wave number range from 1 (stretching vibration) peak is C 18 ~ C 26 as the CH stretching vibration peak of a methylene (CH 2) an aliphatic hydrocarbon, 18 to 22 It was confirmed that C 18 -C 26 aliphatic hydrocarbons were chemically bonded to gelatin. The stretching vibration of CH is about 2920 cm -1 at CH The asymmetrical stretch vibration peak and the CH symmetrical stretch vibration peak at about 2,853 cm -1 are analyzed. The wave number in the FT-IR spectrum may have an error range in the range of ± 8 cm -1 .
It was confirmed that the FT-IR spectra of the hydrogel particles of
The production examples and the experimental examples of the above-mentioned experimental samples are provided for the purpose of understanding the invention and the technical idea of the invention is not limited to the production examples and the experimental examples of the above-mentioned experimental samples. Substitutions, additions, deletions, and the like of other elements within the scope of not hurting the technical idea of the invention will still be included in the present invention and constitute the contents of the invention.
Claims (20)
At least one C 18 aliphatic hydrocarbon derivative of an alkylamine and alkyl amide combined with the biodegradable polymer,
A hydrogel particle having an FT-IR spectrum in which a CH stretching vibration peak of methylene (CH 2 ) in a C 18 aliphatic hydrocarbon appears in a wave number range of 2850 cm -1 to 3000 cm -1 .
Wherein said C 18 aliphatic hydrocarbon derivative is a derivative of C 18 n-alkyl.
Wherein said alkylamine is a C 18 n-alkylamine.
Wherein the C 18 n-alkylamine is octadecylamine.
Wherein the alkyl amide is a C 18 n-alkyl amide.
Wherein the C 18 n-alkyl amide is octadecane amide.
When 5120 parts by weight of iodinated C 18 fatty acid ester is added to 100 parts by weight of the hydrogel particles,
The hydrogel particles, the average amount of water absorption of the iodide C 18 fatty acid ester to be absorbed into the hydrogel particle is more than 50% by weight, based on the amount of the iodide C 18 fatty acid esters.
When 5120 parts by weight of iodinated C 18 fatty acid ester is added to 100 parts by weight of the hydrogel particles,
The hydrogel particles, the average amount of water absorption of the iodide C 18 fatty acid ester to be absorbed into the hydrogel particles exceeds 70% by weight, based on the amount of the iodide C 18 fatty acid esters.
When 5120 parts by weight of iodinated C 18 fatty acid ester is added to 100 parts by weight of the hydrogel particles,
Wherein the average value of the average absorption amount of the iodinated C 18 fatty acid ester absorbed by the hydrogel particles is more than 85% by weight and less than 88% by weight based on the added amount of the iodinated C 18 fatty acid ester.
At least one C18 aliphatic hydrocarbon derivative of an alkylamine and an alkylamide bonded to the biodegradable polymer,
When 5120 parts by weight of iodinated C 18 fatty acid ester is added to 100 parts by weight of the hydrogel particles,
The hydrogel particles, the average amount of water absorption of the iodide C 18 fatty acid ester to be absorbed into the hydrogel particle is more than 50% by weight, based on the amount of the iodide C 18 fatty acid esters.
The hydrogel particles, the average amount of water absorption of the iodide C 18 fatty acid ester to be absorbed into the hydrogel particles exceeds 70% by weight, based on the amount of the iodide C 18 fatty acid esters.
Wherein the average value of the average absorption amount of the iodinated C 18 fatty acid ester absorbed by the hydrogel particles is more than 85% by weight and less than 88% by weight based on the added amount of the iodinated C 18 fatty acid ester.
Iodinated C 18 fatty acid esters;
≪ / RTI >
Wherein the iodinated C18 fatty acid ester is ethyl monoiodostearate.
To 100 parts by weight of the hydrogel particles, 5120 parts by weight of iodinated C 18 fatty acid ester was added to absorb the iodinated C 18 fatty acid ester to the hydrogel particles. Then, phosphate buffered saline (PBS) was added thereto and centrifuged to remove the supernatant If you do,
The C 18 average iodide content of the residual iodide C 18 A composite embolic material exceeding 25% by weight based on the amount of fatty acid ester of a fatty acid ester remaining in the hydrogel particles.
To 100 parts by weight of the hydrogel particles, 5120 parts by weight of iodinated C 18 fatty acid ester was added to absorb the iodinated C 18 fatty acid ester to the hydrogel particles, followed by addition of phosphate buffered saline (PBS), centrifugation, If you do,
The C 18 average iodide content of the residual iodide C 18 A composite embolic material exceeding 35% by weight, based on the amount of fatty acid ester of a fatty acid ester remaining in the hydrogel particles.
To 100 parts by weight of the hydrogel particles, 5120 parts by weight of iodinated C 18 fatty acid ester was added to absorb the iodinated C 18 fatty acid ester to the hydrogel particles. Then, phosphate buffered saline (PBS) was added thereto and centrifuged to remove the supernatant If you do,
Wherein the average residual amount of the iodinated C 18 fatty acid ester remaining on the hydrogel particles is more than 72% by weight and less than 77% by weight based on the amount of the iodinated C 18 fatty acid ester added.
Iodinated C 18 fatty acid ester,
The addition of iodide C 18 fatty acid ester 5120 parts by weight to 100 parts by weight of the hydrogel particles, greater than 50% by weight of the average amount of water absorption of the iodide C 18 fatty acid ester to be absorbed into the hydrogel particles, based on the amount of the iodide C 18 fatty acid ester ego,
To 100 parts by weight of the hydrogel particles, 5120 parts by weight of iodinated C 18 fatty acid ester was added to absorb the iodinated C 18 fatty acid ester to the hydrogel particles. Then, phosphate buffered saline (PBS) was added thereto and centrifuged to remove the supernatant the C 18 average iodide content of the residual composite embolic material exceeding 25% by weight, based on the amount of the iodide C 18 fatty acid ester of a fatty acid ester remaining in the hydrogel particles if.
The C 18 average iodide content of the residual iodide C 18 A composite embolic material exceeding 35% by weight, based on the amount of fatty acid ester of a fatty acid ester remaining in the hydrogel particles.
Wherein the average residual amount of the iodinated C 18 fatty acid ester remaining on the hydrogel particles is more than 72% by weight and less than 77% by weight based on the amount of the iodinated C 18 fatty acid ester added.
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US7476648B1 (en) * | 1999-10-26 | 2009-01-13 | Kaken Pharmaceutical Company, Ltd. | Vessel embolic material comprising hydrogel and therapy with the use thereof |
US20110182998A1 (en) * | 2010-01-27 | 2011-07-28 | Biosphere Medical, Inc. | Microspheres useful for therapeutic vascular embolization |
US20130195988A1 (en) * | 2010-09-08 | 2013-08-01 | Shanghai Cancer Institute | Vascular embolization gelling agent for sustained release of drugs for treating tumors and method for preparing the same |
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US7476648B1 (en) * | 1999-10-26 | 2009-01-13 | Kaken Pharmaceutical Company, Ltd. | Vessel embolic material comprising hydrogel and therapy with the use thereof |
KR100835898B1 (en) * | 2006-12-27 | 2008-06-09 | (재)대구경북과학기술연구원 | Poly vinyl alcohol hydrogel particle by using acid hydrolysis and method the same |
US20110182998A1 (en) * | 2010-01-27 | 2011-07-28 | Biosphere Medical, Inc. | Microspheres useful for therapeutic vascular embolization |
US20130195988A1 (en) * | 2010-09-08 | 2013-08-01 | Shanghai Cancer Institute | Vascular embolization gelling agent for sustained release of drugs for treating tumors and method for preparing the same |
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