WO2016093412A1 - Gelatin sponge containing phosphate buffer solution (pbs) or phosphate buffer and applied to transcatheter arterial chemoembolization, and method for preparing same - Google Patents

Abstract

The present invention relates to a gelatin sponge containing a phosphate buffer solution (PBS) or phosphate buffer and applied to transcatheter arterial chemoembolization, and a method for preparing the same and, more specifically, to a gelatin sponge containing a phosphate buffer solution (PBS) or phosphate buffer and applied to transcatheter arterial chemoembolization, and a method for preparing the same, wherein the method comprising: a step of immersing a gelatin sponge in a phosphate buffer solution (PBS) or phosphate buffer at 4-37°C for 3-12 hours; a step of freeze-drying the gelatin sponge, which is impregnated with the phosphate buffer solution (PBS) or phosphate buffer, at a temperature condition of -10°C to -35°C for 30 minutes to 16 hours; a step of pulverizing the freeze-dried gelatin sponge; a step of separating the pulverized gelatin sponge into sizes of 10-100 μm, 100-300 μm, 300-500 μm, and 500-700 μm, respectively, wherein, after the pulverized gelatin sponge is transferred to a hospital while being kept in disinfected vials, or in package containers in which the pulverized gelatin sponge is stored in any one of a phosphate buffer solution and a phosphate buffer, the pulverized gelatin sponge is bound to physiological saline, distilled water, and an anticancer agent, which are introduced thereto, to be used as a therapeutic agent for liver cancer.

Description

[Revision according to Rule 26.05.01.2015] Gelatin sponge containing phosphate buffer solution (PBS) or phosphate buffer applied to carotid artery embolization and preparation method thereof

The present invention relates to a gelatin sponge containing a phosphate buffer solution (PBS) or a phosphate buffer (Phosphate Buffer) applied to carotid artery embolization and a method for preparing the same, and more specifically, a phosphate buffer solution (PBS) at 4 ° C. to 37 ° C. ) Or immersing the gelatin sponge in a phosphate buffer (Phosphate Buffer) for 3 to 12 hours, and the gelatin sponge in which the ginseng buffer buffer (PBS) or the phosphate buffer (Phosphate Buffer) is precipitated -10 ° C to -35 ° C. Lyophilizing for 30 minutes to 16 hours at temperature conditions, pulverizing the lyophilized gelatin sponge, and 10 to 100 μm, 100 to 300 μm, 300 to 500 μm, 500 to 500 μm After being separated into a size of 700 μm, the crushed gelatin sponge is delivered to the hospital in a sterilized vial bottle, a phosphate buffer solution or a phosphate buffer solution, and then delivered to a hospital, followed by physiological saline, distilled water and anticancer. As it will be bonded to each other input of the phosphate buffer solution (PBS) or a phosphate buffer, the gelatin sponge and a method comprising (Phosphate Buffer) applied to the carotid artery embolization chemical configured to be used as a liver cancer therapeutic agent.

In general, liver cancer is one of the most common cancers in the world, especially in men.

The main causes of liver cancer are chronic hepatitis caused by the hepatitis B virus and chronic hepatitis caused by the hepatitis C virus, and as a result of chronic hepatitis caused by these viruses, hepatic cirrhosis occurs and liver cancer develops as long-term inflammation progresses.

In addition, chronic liver diseases such as alcoholic liver disease or liver damage caused by toxins such as aflatoxin may all cause liver cancer.

Liver cancer is very fast, so early screening is important. For the treatment of liver cancer, surgical removal of the cancerous tissue, method of transarterial chemoembolzation, and percutaneous ethanol injection And radiofrequency thermal ablation to kill cancer cells, but these methods are not effective when the size of liver cancer is too large, large blood vessels are involved, or cancer has spread to other organs. There are disadvantages.

In addition, liver cancer treatment includes liver resection, liver transplantation, and local therapy (high-frequency rupture, topical, alcohol injection) .However, more than 50% of patients with hepatocellular carcinoma are diagnosed at advanced stage or advanced cirrhosis. Embolization, targeted therapy anticancer agent. The role of non- radical treatment, such as external radiation therapy, is also important.

Therefore, there is a method for treating liver cancer using drug-releasing microspheres, which is a new carotid artery treatment among the carotid artery embolization, which is a part of the treatment of non-basement liver cancer.

Here, drug-releasing microspheres are embolization materials that combine 100-700 μm microspheres with anticancer drugs to treat liver cancer using the hepatic artery. Existing drug-releasing microspheres are permanent embolic substances in the form of beads made of polyvynil alcohol. As hepatic blood vessels are severely damaged and hepatic blood vessels are permanently blocked, hepatic cancer with high recurrence rate is increased when chemoembolization is attempted.

At this time, if the microspheres are decomposed after the treatment of liver cancer, hepatic artery damage is small and the hepatic blood vessels are not permanently blocked, and if relapses, chemoembolization can be attempted again using the hepatic artery.

Therefore, it is urgent to develop drug release microspheres that are particularly effective for liver cancer without impairing liver function.

In order to solve the above problems, phosphate buffer solution (PBS) applied to carotid artery chemoembolization, which is configured to treat liver cancer by using hepatic artery as embolic material by combining anticancer agent with gelatin sponge embolism material or It relates to a gelatin sponge containing a phosphate buffer (Phosphate Buffer) and a preparation method thereof.

In order to achieve the above object, a process of immersing gelatin sponge in a phosphate buffer solution (PBS) or phosphate buffer (PBS) or phosphate buffer at 4 ° C. to 37 ° C. for 3 to 12 hours, and the ginseng buffer solution (PBS) or phosphate A process of freeze-drying the gelatin sponge on which the Phosphate Buffer is precipitated for 30 minutes to 16 hours at a temperature condition of -10 ° C to -35 ° C, grinding the freeze-dried gelatin sponge, and the pulverized gelatin sponge After separating into 10 ~ 100㎛, 100 ~ 300㎛, 300 ~ 500㎛, 500 ~ 700㎛ size, respectively, disinfected vials, phosphate buffer solution, phosphate buffer solution in the packaging container in any one of the hospital After delivery to physiological saline, distilled water and anticancer agents are added to each other and combined with each other to contain a phosphate buffer solution (PBS) or phosphate buffer (Phosphate Buffer) applied to the carotid artery embolization to be used as a liver cancer treatment It relates to a gelatin sponge and its preparation method.

The present invention is a microsphere that is broken down in the body, when injected into the liver for the treatment of liver cancer, the microspheres are broken down in the body after a period of time, during this period to prevent blood supplied to the hypervascularized malignant tumor and local to the tumor As drug release microspheres are decomposed, drugs are continuously delivered to the tumor (Drug Delivery) to reduce side effects due to the influx of systemic blood flow of anticancer drugs and to increase tumor response.

And, when liver cancer patients with high recurrence rate need to be re-treated, there is an effect that can be performed chemoembolization using drug-release microspheres again.

1 is a work flow diagram schematically showing the work process of the present invention.

Figure 2 is a perspective view showing the gelatin sponge which is the main part of the present invention.

Figure 3 (a) is a perspective view schematically showing a state in which the main portion of the present invention gelatin sponge immersed in phosphate buffer solution (PBS).

Figure 3 (b) is a perspective view schematically showing a state in which the main portion of the present invention gelatin sponge immersed in a phosphate buffer (Phosphate Buffer).

Figure 4 is a perspective view showing a state in which the crushed gelatin sponge immersed in phosphate buffer (PBS) or phosphate buffer (Phosphate Buffer) that is the main part of the present invention, and then crushed into powder.

Figure 5 is a perspective view of the packaged in a vial bottle in a state that is crushed into a powder after cooling the gelatin sponge which is the main part of the present invention.

Figure 6 is a perspective view schematically showing a state in which physiological saline or distilled water and an anticancer agent are coupled to a gelatin sponge stored in a vial bottle which is a main part of the present invention.

DETAILED DESCRIPTION Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings so that those skilled in the art may easily implement the present invention. As those skilled in the art would realize, the described embodiments may be modified in various different ways, all without departing from the spirit or scope of the present invention.

In the drawings, parts irrelevant to the description are omitted for simplicity of explanation, and like reference numerals designate like parts throughout the specification.

Throughout the specification, when a part includes a certain component, this means that it may further include other components rather than controlling other components unless otherwise stated.

First, the present invention forms a gelatin sponge 10 containing a phosphate buffer solution (PBS) 20 or a phosphate buffer (Phosphate Buffer) 30 to be applied to carotid artery embolization as shown in FIGS. Done.

Here, the gelatin sponge 10 is impregnated with a phosphate buffer solution (PBS) 20 or a phosphate buffer (Phosphate Buffer) 30 of 4 ℃ ~ 37 ℃ is subjected to a process of immersion for 3 to 12 hours.

In addition, the gelatin sponge 10 in which the ginseng salt buffer solution (PBS) 20 or the phosphate buffer (Phosphate Buffer) 30 is precipitated is frozen at -10 ° C to -35 ° C for 30 minutes to 16 hours. The process of making the water present 10% ~ 20% through the drying process,

Here, in another working process of the present invention, the gelatin sponge 10 in which the ginseng salt buffer solution (PBS) 20 or the phosphate buffer (Phosphate Buffer) 30 is precipitated is minus −10 ° C. to −35 ° C. By the process of freeze-drying for 16 to 48 hours, the process to ensure the presence of 0% to 10% of moisture is carried out according to the work order.

Next, the process of grinding the lyophilized gelatin sponge 10 is in progress.

In addition, the crushed gelatin sponge (10) is separated through a mesh (not shown) to the specifications of 10 ~ 100㎛, 100 ~ 300㎛, 300 ~ 500㎛, 500 ~ 700㎛, respectively, sterilized vial bottle It will go through the packaging process.

As described above, the present invention may be packaged after immersing and freezing the gelatin sponge 10 in the phosphate buffer solution 20 or the phosphate buffer (Phosphate Buffer) (30), after the grinding and drying operation.

On the other hand, in the normalized state by cutting the gelatin sponge 10 that has not been frozen

After immersing in phosphate buffer solution (PBS) 20 or phosphate buffer (Phosphate Buffer) 30 of 4 ℃ ~ 37 ℃ for 3 to 12 hours, it may be combined with an anticancer agent.

Then, the gelatin sponge 10 pulverized according to the standard is delivered to the hospital in the packaging container in any one of the sterilized vial bottle or phosphate buffer solution, phosphate buffer solution, physiological saline, distilled water and anticancer drugs are combined with each other It can be used as a treatment for liver cancer.

On the other hand, the gelatin sponge 10 in which the phosphate buffer solution (PBS) 20 or the phosphate buffer (Phosphate Buffer) 30 is deposited is dehumidified, nitrogen dried, cold air dried, vacuum dried, or natural dried in addition to the freeze drying method. Any one can be dried.

That is, the present invention can be combined with the anti-cancer drug gelatin embolic material to treat liver cancer by using the hepatic artery as an embolic material.

In addition, it is a microsphere that breaks down in the body when injected into the liver for the treatment of liver cancer, a microsphere that breaks down in the body after a certain period of time, during this period to prevent blood supply to the hypervascularized malignant tumor and localized to the tumor As drug release microspheres are broken down, drugs are continuously delivered to the tumor, thereby reducing side effects due to the influx of systemic blood flow of anticancer drugs and increasing tumor response.

And, if hepatic cancer patients with high recurrence rate needs to be retreated, chemoembolization using drug-release microspheres can be performed again.

Referring to the work process of the present invention made of the above configuration step by step as follows.

A first step of immersing gelatin sponge in a phosphate buffer solution (PBS) 20 or a phosphate buffer (Phosphate buffer) 30 at 4 ° C. to 37 ° C., and soaking for 3 to 12 hours;

Gelatin Sponge precipitated in the Ginseng Salt Buffer Solution (PBS) 20 or Phosphate Buffer (30) was lyophilized for 30 minutes to 16 hours at -10 ° C. to -35 ° C. The second process to have 20% moisture,

A third step of grinding the lyophilized gelatin sponge,

The pulverized gelatin sponge was separated into sizes of 10 to 100 μm, 100 to 300 μm, 300 to 500 μm, and 500 to 700 μm by using a mesh, and then the sterilized vial bottle or the crushed gelatin sponge was used as a phosphate buffer solution. It may be made through a fourth process of delivering to the hospital in the packaging container state contained in any one of the phosphate buffer solution.

Another working process of the present invention is as follows.

A first step of immersing gelatin sponge in a phosphate buffer solution (PBS) 20 or a phosphate buffer (Phosphate buffer) 30 at 4 ° C. to 37 ° C., and soaking for 3 to 12 hours;

The ginseng buffer buffer (PBS) (20) or phosphate buffer (Phosphate Buffer) (30) precipitated gelatin sponge was freeze-dried for 16 to 48 hours at -10 ℃ ~ -35 ℃ temperature conditions 0% ~ 10 The second step of having a moisture of%,

A third step of grinding the lyophilized gelatin sponge,

The crushed gelatin sponge is separated into sizes of 10 to 100 μm, 100 to 300 μm, 300 to 500 μm, and 500 to 700 μm using a mesh, and then packaged in sterile vial bottles, or pulverized. The gelatin sponge can be made through a fourth process of delivering to the hospital in the packaging container state contained in any one of the phosphate buffer solution, phosphate buffer solution.

That is, the present invention can freeze by immersing the gelatin sponge in a phosphate buffer solution or phosphate buffer (Phosphate Buffer) through the above-described process, after grinding and drying operation, to obtain a packaged product.

On the other hand, the gelatin sponge 10 in which the phosphate buffer solution (PBS) 20 or the phosphate buffer (Phosphate Buffer) 30 is deposited is dehumidified, nitrogen dried, cold air dried, vacuum dried, or natural dried in addition to the freeze drying method. Any one can be dried.

Another working process of the present invention is as follows.

Standardizing by cutting gelatin sponges in the unfrozen state,

The standardized gelatin sponge may be immersed in phosphate buffer solution (PBS) 20 or phosphate buffer (Phosphate Buffer) 30 at 4 ° C. to 37 ° C. for 3 to 12 hours, and then the anticancer agent may be combined.

Then, the gelatin sponge 10 pulverized by the standard is delivered to the hospital packaging container contained in any one of the sterilized vial bottle or phosphate buffer solution, phosphate buffer solution, physiological saline, distilled water and an anticancer agent is coupled to each other Will be used as a liver cancer treatment.

As described above, the present invention is a microsphere that is decomposed in the body, and when injected into the liver for the treatment of liver cancer, the microspheres are decomposed in the body after a certain period of time. As drug release microspheres are decomposed in a local manner, drugs are continuously delivered to the tumor (Drug Delivery) to reduce side effects due to systemic blood flow of anticancer drugs and to increase tumor response.

And, when liver cancer patients with high recurrence rate need to be re-treated, there is an effect that can be performed chemoembolization using drug-release microspheres again.

The foregoing description of the present invention is intended for illustration, and it will be understood by those skilled in the art that the present invention may be easily modified in other specific forms without changing the technical spirit or essential features of the present invention. will be.

Therefore, it should be understood that the embodiments described above are exemplary in all respects and not restrictive. For example, each component described as a single type may be implemented in a distributed manner, and similarly, components described as distributed may be implemented in a combined form.

The scope of the present invention is shown by the following claims rather than the detailed description, and all changes or modifications derived from the meaning and scope of the claims and their equivalents should be construed as being included in the scope of the present invention.

Claims (6)

1. Phosphate buffer solution applied to carotid artery embolization, characterized in that gelatin sponge 10 immersed in phosphate buffer solution (PBS) 20 or phosphate buffer (30) is formed to be combined with an anticancer agent ( PBS) or gelatin sponge containing Phosphate Buffer.
2. The method of claim 1,

   To form a gelatin sponge 10 immersed in the phosphate buffer (PBS) (20) or phosphate buffer (Phosphate Buffer) (30),

   After the gelatin sponge 10 is frozen, the gelatin sponge 10 pulverized with the pulverization treatment is delivered to the hospital in a package container in a sterilized vial bottle or phosphate buffer solution, phosphate buffer solution, Phosphate buffer solution (PBS) or phosphate buffer (Phosphate Buffer) that is applied to carotid artery chemoembolization, characterized in that the saline, distilled water and anticancer agents are combined with each other to be used as a treatment for liver cancer. .
3. The method of claim 1,

   The gelatin sponge 10 in which the phosphate buffer solution (PBS) 20 or the phosphate buffer (Phosphate Buffer) 30 is deposited is dehumidified, nitrogen dried, cold air dried, vacuum dried, or natural dried in addition to freeze drying. A gelatin sponge containing a phosphate buffer solution (PBS) or a phosphate buffer (Phosphate Buffer) applied to carotid artery embolization, characterized in that it is configured to be dried as one.
4. The gelatine sponge is cut and standardized without being frozen, and the gelatine sponge is placed in a phosphate buffer (PBS) 20 or a phosphate buffer 30 at 4 ° C. to 37 ° C. for 3 to 12 hours. After immersion, gelatin sponge containing phosphate buffer solution (PBS) or phosphate buffer (Phosphate Buffer) applied to the carotid artery chemoembolization, characterized in that configured to bind the anticancer agent.
5. A first step of immersing gelatin sponge in a phosphate buffer solution (PBS) 20 or a phosphate buffer (Phosphate buffer) 30 at 4 ° C. to 37 ° C., and soaking for 3 to 12 hours;

   Gelatin sponge with precipitated ginseng salt buffer solution (PBS) (20) or phosphate buffer (30) (30) was lyophilized for 30 minutes to 16 hours at -10 ° C to -35 ° C temperature, 10% to 20% The second step of having a moisture of

   A third step of grinding the lyophilized gelatin sponge,

   The crushed gelatin sponge is separated into sizes of 10 to 100 μm, 100 to 300 μm, 300 to 500 μm, and 500 to 700 μm using a mesh, and then any of a sterilized vial bottle or a phosphate buffer solution or a phosphate buffer solution. Phosphate buffer solution (PBS) or phosphate buffer (Phosphate Buffer) applied to the carotid artery embolization, characterized in that it is configured to be made through the fourth process to deliver to the hospital in a packaging container contained in one of the gelatin sponge Manufacturing method.
6. A first step of immersing gelatin sponge in a phosphate buffer solution (PBS) 20 or a phosphate buffer (Phosphate buffer) 30 at 4 ° C. to 37 ° C., and soaking for 3 to 12 hours;

   Gelatin Sponge on which Ginseng Salt Buffer (PBS) (20) or Phosphate Buffer (30) was precipitated was lyophilized at -10 ° C to -35 ° C for 16 to 48 hours, and 0% to 10% A second step of having moisture,

   A third step of grinding the lyophilized gelatin sponge,

   The crushed gelatin sponge is separated into sizes of 10 to 100 μm, 100 to 300 μm, 300 to 500 μm, and 500 to 700 μm using a mesh, and then any of a sterilized vial bottle or a phosphate buffer solution or a phosphate buffer solution. Phosphate buffer solution (PBS) or phosphate buffer (Phosphate Buffer) applied to the carotid artery embolization, characterized in that it is configured to be made through the fourth process to deliver to the hospital in a packaging container contained in one of the gelatin sponge Manufacturing method.

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