KR100581228B1 - Process of an injection type solid chitosan - Google Patents

Abstract

The present invention relates to a method for producing a solid state chitosan powder which can be injected into the human body to give a volume replacement effect of the soft tissue, and by scattering chitosan aqueous solution by ultrasonic vibration or spray, it is immersed in low temperature isopropyl alcohol (isoprophyl alcohol) To obtain a precipitate and freeze it.

Chitosan, Body Injection, Breast Augmentation, Sponge Structure, Freeze Drying, Chitosan Crystal

Description

Process for producing solid chitosan powder that can be injected into human body by injection {Process of an injection type solid chitosan}

The present invention relates to a method for producing a chitosan powder in a solid state that can be injected into the human body to give a volume replacement effect of the soft tissue.

Chitosan that can be used as an injection for the purpose of replacing soft tissues of the human body and a preparation method thereof have been described by Korean Patent Publication No. 1020020012004.

The above technique provides a solid chitosan having a sponge structure as an injectable substance to fill the volume of soft tissues, such as breast augmentation, and the chitosan powder is heated to a high pressure state as a method for producing the solid chitosan. After depressurizing it instantaneously, a vacuum expansion method for forming a microbubble group in the particles, a mixture of chitosan particles and distilled water, sprayed using a spray, spray sinter freeze drying method for quenching and freeze-drying, chitosan particles and distilled water Ultrasonic freeze-drying drying is performed by applying ultrasonic vibration to the mixed mixture, followed by quenching and freeze drying.

The solid chitosan is a micro-bubble formed in the chitosan particles having a size of 50-250㎛, which is large enough to pass through the syringe needle, the macrophages can not be observed, thereby providing a growth space for the cells within the particles to soften the soft tissue It is characterized by a configuration to be replaced, and as a method for producing chitosan of such a structure, a pressure-expansion expansion method, a spray fly freeze drying method, an ultrasonic fly freeze drying method is proposed.

The method for preparing each chitosan powder is characterized in that the chitosan powder is pressurized or sprayed in an aqueous solution in which distilled water is mixed with the powder. The chitosan lump in a solid state has a particle size of 25-40 μm. By using a solid chitosan powder obtained by the process of grinding into a powder, and lyophilizing to form a microbubble group in the powder, the chitosan powder required by a relatively simple equipment can be produced or in some cases Each process is carried out separately, there is a disadvantage that mass production is limited because it uses chitosan powder.

The present invention supplements the preparation method of chitosan powder described above in preparing chitosan powder which can be injected into the human body as an injection, and has a size of 250 μm or less through freezing, freezing drying and screening process using chitosan in aqueous solution. By presenting a method for producing chitosan powder or crystals having a microbubble group, it is possible to sort according to the size of the particles, uniform quality, process shortening and mass production.

To this end, the present invention provides a solid chitosan powder of 250 μm or less in which a microbubble group is formed as an injectable substance used as an injectable agent to fill a volume by replacing soft tissues such as injection, cell culture, and breast enlargement bag. Using a chitosan aqueous solution, which has undergone purification and neutralization, it is powdered to form a microbubble group therein, and it is characterized in that it is selected to a size of less than 250㎛.

 The aqueous chitosan solution is prepared by dissolving the chitosan mass using an acetic acid solvent, purified by administering caustic soda, and neutralizing the chitosan solution by a known method for producing an aqueous chitosan solution.

The method of pulverizing the microbubble group therein is a method of pulverizing the aqueous chitosan solution in a frozen state and lyophilizing it in an ice powder, or freezing and drying the chitosan aqueous solution to make a chitosan sponge mass. How to break into fine particles, or the chitosan aqueous solution by ultrasonic vibration to make a mist (mist) and cooling it to make ice chitosan in the form of powder and freeze-dried, or by ultrasonic vibration or spraying chitosan aqueous solution In addition, various methods are applied, such as a method of obtaining a precipitate by immersing it in a low temperature isopropyl alcohol.

Screening of chitosan powder is a process of selecting chitosan powder having a microbubble group having a size of 20-250 μm as a body injection material used as an injection, and passing the chitosan powder through a double filter.

The double filter separates the large size filter which cannot pass chitosan powder larger than 250 μm from the small size filter which only passes chitosan powder smaller than 20 μm to shoot chitosan powder or vibrate the filter. By extracting chitosan powder between the large filter and the small filter, the chitosan powder having a size of 20-250 μm can be extracted.

The minimum size of the chitosan powder is 20 μm, which is smaller than the macrophage size (about 50 μm), which is likely to be detected by macrophages but is only a part of the total chitosan powder, and is larger than 50 μm. By being in a mixed state with the likelihood of being devoured is lowered, there is an advantage that can increase the yield for the feedstock.

The selection of the chitosan powder is to meet the required size of the chitosan powder, which is selected before lyophilization according to the powdering method and lyophilized in the next step to obtain the chitosan powder, or in the final step after lyophilization. It will be possible to obtain an alluvial chitosan powder.

Hereinafter, the present invention will be described in more detail with reference to specific examples.

Example 1

Administering the purified chitosan solid to acetic acid and caustic soda to produce an aqueous chitosan solution, and freezing at sub-zero temperatures to form ice chunks; and abrasion (or miller) the ice chunks. Pulverizing into fine particles using the fine particles, passing the crushed ice powder through a double filter to screen an ice powder having a size of 20-250 μm, and lyophilizing the ice powder to produce a chitosan powder. do.

The chitosan powder prepared by the above method has a sponge structure in which a fine bubble group is formed by the water escaped from the inside while being solidified by the freeze-drying process in the process of crushing into ice powder in an ice state. , The size of the bubble group formed therein can be adjusted according to the freeze-drying temperature, has a size of about 10-50㎛.

The manufacturing method is a chitosan aqueous solution, consisting of ice mass production, crushing, screening and freeze-drying process is possible to carry out a continuous process, it is possible to manufacture a large amount of chitosan powder, crushing size can be quantified, The use of an easy ice form has the advantage of producing a solid chitosan powder of uniform quality.

Example 2

Freezing the completely purified and neutralized aqueous chitosan solution at sub-zero temperature to form an ice mass, crushing the ice mass into fine particles using an abraser (or miller), and lyophilizing the ice powder to form a solid chitosan A chitosan powder is prepared by obtaining a powder and selecting a chitosan powder having a size of 20-250 μm by passing a solid chitosan powder through a double filter.

Compared with Example 1, the above-described method was lyophilized first, followed by screening by a filter to obtain chitosan powder having a size of 20-250 μm, thereby obtaining the same result as Example 1.

Example 3

Freezing the fully purified and neutralized aqueous chitosan solution at sub-zero temperature to form an ice mass, lyophilizing the ice mass to prepare a chitosan sponge mass, and using the abraser (or miller) to form the sponge mass. The chitosan powder is prepared by the step of pulverizing with the above, and by selecting the chitosan powder having a size of 20-250 μm by passing the fine particles through a double filter.

The above example is a method of preparing chitosan powder required by crushing and screening after freeze drying in an ice mass, but the manufacturing method has a simple advantage, but takes a long time of freeze drying, but rather coarse particles such as cell culture. It can be usefully used in the field using chitosan powder.

Example 4

 Spraying the fully purified and neutralized aqueous chitosan solution with nitrogen gas to contact the low temperature isoprophyl alcohol solution to precipitate in the form of fine ice, separating the precipitate to freeze drying, and double-filtering the dried chitosan powder It is a method for producing a chitosan powder having a size of 20-250㎛ by passing through.

The spraying of the chitosan aqueous solution is made by a method such as ultrasonic vibration or spray, and sprayed with nitrogen gas to diffuse and condense the contact with the isoprophyl alcohol solution in the form of snow crystals.

The isoprophyl alcohol solution has a low freezing point and freezes the chitosan without melting it, so that the pure chitosan particles are frozen.They can freeze and precipitate the fine chitosan particles by maintaining the temperature of about -70 ℃. have.

Precipitated chitosan particles have a higher specific gravity than isoprophyl alcohol solution, so they accumulate in the form of precipitates on the bottom.

When freeze-drying the frozen chitosan powder, water in the form of ice contained in the particles rises in the form of water vapor so that numerous bubbles are formed inside the chitosan particles, and the shape is crystallized to form a single frame and branching pod. It has a crystal structure.

Therefore, the solid chitosan powder produced according to the above-described embodiment has a certain amount of bubbles formed therein like the chitosan powder prepared in Examples 1 to 3, and on the other hand, due to the crystal structure of the frame and branches When kneading an injection for injection into the body, a gap is formed between each solid chitosan particle, which acts as a space in which cells grow or are filled with biological tissue.

The present invention has the effect of selecting a method for producing a solid chitosan powder in accordance with the equipment or production conditions by presenting a variety of methods for producing a solid chitosan powder that can be injected into the human body as an injection, solid chitosan powder by a more automated process By making it possible to have the effect of enabling the production of solid chitosan powder of more uniform quality economically.

Claims (1)

As an injectable substance used as an injectable agent to replace the soft tissues such as injection, cell culture, and breast enlargement bag to fill the volume, it is purified and neutralized in the manufacture of a solid chitosan powder of 250 μm or less in which microbubbles are formed. Diffusion spraying with aqueous chitosan solution nitrogen to contact a low temperature isopropyl alcohol solution to precipitate in fine ice form; Separating and freeze drying the precipitate to obtain chitosan crystals having fine frames and branches; A large-size filter by passing a large-sized filter that cannot pass chitosan crystals larger than 250 μm and a small-sized filter that only passes chitosan powder smaller than 20 μm through a double filter spaced apart from each other. And extracting chitosan powder between the small standard filter; manufacturing a chitosan powder by injection;