KR20230059163A - Natural polymer support comprising chondroitin sulfate and hyaluronic acid for regenerating and substituting cartilage and process for preparing the same - Google Patents

Abstract

The present invention relates to a natural polymer support composition for cartilage regeneration or replacement containing cross-linked hyaluronic acid and a method for manufacturing the same. Specifically, the natural polymer support composition for cartilage regeneration or replacement includes hyaluronic acid and chondroitin sulfate, and the preparation method may include a step of mixing hyaluronic acid and chondroitin sulfate. The present invention prevents rupture of articular cartilage with a cross-linked product of chondroitin sulfate and hyaluronic acid, and uses cross-linking to replace the wear and mechanical durability of a substitute with the strength of cartilage in the body, thereby being effective in treating cartilage damage and pain by preventing wear and promoting the function and elasticity of cartilage, which is the function of cartilage substitutes in the body. Due to a cross-linked product of highly biocompatible hyaluronic acid and chondroitin sulfate, which is a major component of bone and cartilage, long-term viability, function, and cartilage protection effects are provided without rejection or immune response in vivo. Through injection of a combined cross-linked product of chondroitin sulfate and hyaluronic acid, the synergistic effect reduces pain caused by friction and an improved environment can be provided as a substitute for cartilage through highly biocompatible materials.

Description

Natural polymer scaffold for cartilage regeneration and replacement containing chondroitin sulfate and hyaluronic acid and method for preparing the same

The present invention relates to a natural polymer scaffold for cartilage regeneration and replacement containing chondroitin sulfate and hyaluronic acid and a method for preparing the same.

Hyaluronic acid is a linear polymer in which β-N-acetyl-D-glucosamine and β-D-glucuronic acid are alternately bonded, and is a polysaccharide having a molecular weight of 50,000 to 10,000,000 Da or more. Hyaluronic acid is a basic substance of biological connective tissue, mainly mammalian skin, synovial fluid of joints, vitreous humor of eyes, umbilical cord, serum, and cock's comb. ), etc., and it is known to exist in the capsular membrane of streptococci. Common methods for obtaining hyaluronic acid include extraction from chicken combs, umbilical cords, etc., culturing streptococcal lancefield groups A and C, genetically recombined Bacillus subtilis (B. subtilis), and then extracting and purifying method, etc.

Natural hyaluronic acid is polydisperse acidic in proportion to its molecular weight, has no specificity between species, and does not have tissue or organ specificity, so it shows excellent biocompatibility when transplanted or injected into a living body regardless of its origin. etc. are used.

However, since hyaluronic acid is easily decomposed by an enzyme called hyaluronidase present in the body, the half-life in living tissue is relatively short, such as 0.5 - 3 days, and natural polymers are directly used as medical materials. There are limits to what you can do. Therefore, in order to expand its use as a medical material, it is attempted to improve the durability in the body by cross-linking hyaluronic acid using various chemical modifiers or modifying it by attaching functional groups. has been

Representative of these are highly swellable crosslinked hyaluronic acid gels obtained using difunctional crosslinkers such as divinylsulfone, bisepoxide or formaldehyde (USP 4,582,865, JP1994-037575, JP3107488).

Cartilage is a tissue composed of cartilage cells and a large amount of matrix surrounding them, and is a concept corresponding to tibia (or bone tissue), a bone whose main component is calcium. The function of cartilage is to prevent friction of the epiphyses, as seen in the articular cartilage covering the epiphyses of joints, to maintain elasticity like trachea and auricle, or to provide resistance to pressure like costal cartilage and pubic symphysis cartilage. can Cartilage is insensitive, avascular, and lymphatic, and once damaged, cannot be restored to its original state. For example, cartilage in joints such as the knee, hip, and temporomandibular joints may be damaged by shock absorption or wear due to degenerative arthritis. In this case, the damaged cartilage does not naturally recover.

Therefore, when the cartilage is worn or damaged, it is necessary to replace the worn or damaged cartilage using an artificial cartilage member or cartilage collected from the body or artificially cultured cartilage.

Problems with materials used as substitutes for corrugated board are as follows. In the case of using carbon fiber, tissues such as cartilage are not formed and fibers are formed. In the case of polyvinyl alcohol hydrogel, there are limitations in reconstitution, fixation method, and fusion with surrounding tissues, and when porous polyester urethane polymer is applied, toxic side effects are exhibited.

In addition, even in the case of the most commonly used collagen meniscus implant, there is a problem in that there is almost no CMI remnant after 5-6 years, or the regenerated tissue in the biopsy test shows a different aspect from cartilage. Therefore, there are still few substitutes that are highly compatible with the body, fuse with surrounding tissues, and show the replacement effect of cartilage.

Republic of Korea Patent No. 10-1027630

An object of the present invention is to provide a composition for combined injection containing chondroitin sulfate, which is a kind of polysaccharide distributed in cartilage or connective tissue of animals, and hyaluronic acid, which provides lubrication and nutrition to cartilage, It is intended to provide a composition that replaces ruptured cartilage.

In order to achieve the above object, the present invention provides a natural polymer scaffold composition for cartilage regeneration or replacement containing hyaluronic acid and chondroitin sulfate.

The hyaluronic acid and chondroitin sulfate are characterized in that they are crosslinked with each other.

The hyaluronic acid and chondroitin sulfate are preferably cross-linked through a cross-linking agent.

The hyaluronic acid and chondroitin sulfate are preferably crosslinked in a weight ratio of 5 to 10%: 4 to 8%.

The crosslinking agent is preferably mixed in an amount of 0.01 to 2% based on the total volume of the composition.

More preferably, the hyaluronic acid, chondroitin sulfate, and crosslinking agent are crosslinked in a weight ratio of 8% to 9%: 6 to 8% by weight, and the crosslinking agent may be mixed in a volume ratio of 0.5 to 0.7% based on the weight of the composition. .

The crosslinker is diamine, divinylsulfone, 1,4-butanediol, diglycidyl ether (BDDE) and glutaraldehyde, carbodiimide, hydroxysuccinimide, imidoester, maleimide, haloacetyl , disulfides, hydroazides, and alkoxyamines.

According to another embodiment of the present invention, a method for preparing a natural polymer scaffold for cartilage regeneration or replacement, comprising mixing hyaluronic acid and chondroitin sulfate, is provided.

The hyaluronic acid and chondroitin sulfate are preferably mixed in a weight ratio of 5 to 10%: 4 to 8%.

After the mixing step, it is preferable to further include adding a crosslinking agent.

The crosslinking agent is preferably mixed in an amount of 0.01 to 2% based on the total volume of the composition.

The crosslinker is diamine, divinylsulfone, 1,4-butanediol, diglycidyl ether (BDDE) and glutaraldehyde, carbodiimide, hydroxysuccinimide, imidoester, maleimide, haloacetyl , disulfides, hydroazides, and alkoxyamines.

The cartilage is preferably any one of ear cartilage, nose cartilage, knee cartilage, elbow cartilage or shoulder cartilage.

In another embodiment of the present invention, a natural polymer scaffold for cartilage regeneration or replacement made of the above composition is provided.

In another embodiment of the present invention, a natural polymer scaffold for cartilage regeneration or replacement manufactured by the above manufacturing method is provided.

The present invention prevents articular cartilage rupture with a crosslinked product of chondroitin sulfate and hyaluronic acid, and uses crosslinking to replace wear and mechanical durability of the substitute with the strength of cartilage in the body. Palpation is effective for cartilage damage and pain.

It is a combination cross-linked product of hyaluronic acid with high biocompatibility and chondroitin sulfate, which is a major component of bone and cartilage, and exhibits long-term viability, function, and cartilage protection effects without rejection or immune response in vivo.

When combined cross-linked product of chondroitin sulfate and hyaluronic acid is injected, synergistic effect reduces pain due to friction and provides an improved environment as a substitute for cartilage with highly biocompatible materials.

1 shows the appearance of a crosslinked hydrogel composition according to an embodiment of the present invention.
2 illustrates rheometer measurement values of a crosslinked hydrogel implant according to an embodiment of the present invention.
3 is a graph showing rheometer measurement values of a crosslinked hydrogel implant according to an embodiment of the present invention.
4 is a graphical representation of the volume change of a crosslinked hydrogel composition.
Figure 5 shows the volume change of the crosslinked hydrogel composition as an MRI picture.

Specific structural or functional descriptions of the embodiments of the present invention disclosed in this specification or application are merely exemplified for the purpose of explaining the embodiments according to the present invention, and the embodiments according to the present invention may be implemented in various forms. and should not be construed as being limited to the embodiments described in this specification or application.

Embodiments according to the present invention can apply various changes and can have various forms, so specific embodiments are illustrated in the drawings and described in detail in the present specification or application. However, this is not intended to limit the embodiments according to the concept of the present invention to a specific disclosed form, and should be understood to include all modifications, equivalents, or substitutes included in the spirit and technical scope of the present invention.

Terms such as first and/or second may be used to describe various components, but the components should not be limited by the terms. The above terms are only for the purpose of distinguishing one component from another component, e.g., without departing from the scope of rights according to the concept of the present invention, a first component may be termed a second component, and similarly The second component may also be referred to as the first component.

It is understood that when an element is referred to as being "connected" or "connected" to another element, it may be directly connected or connected to the other element, but other elements may exist in the middle. It should be. On the other hand, when an element is referred to as “directly connected” or “directly connected” to another element, it should be understood that no other element exists in the middle. Other expressions describing the relationship between elements, such as "between" and "directly between" or "adjacent to" and "directly adjacent to", etc., should be interpreted similarly.

Terms used in this specification are only used to describe specific embodiments, and are not intended to limit the present invention. Singular expressions include plural expressions unless the context clearly dictates otherwise. In this specification, terms such as "comprise" or "having" are intended to designate that the described feature, number, step, operation, component, part, or combination thereof exists, but one or more other features or numbers However, it should be understood that it does not preclude the presence or addition of steps, operations, components, parts, or combinations thereof.

Unless defined otherwise, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention belongs. Terms such as those defined in commonly used dictionaries should be interpreted as having a meaning consistent with the meaning in the context of the related art, and unless explicitly defined herein, they are not interpreted in an ideal or excessively formal meaning. .

The present invention provides a natural polymer scaffold composition for cartilage regeneration or replacement containing hyaluronic acid and chondroitin sulfate.

The hyaluronic acid may have a molecular weight of 800,000 to 2,500,000.

The hyaluronic acid and chondroitin sulfate are characterized in that they are crosslinked with each other.

The hyaluronic acid and chondroitin sulfate are preferably cross-linked through a cross-linking agent.

The hyaluronic acid and chondroitin sulfate are preferably crosslinked in a weight ratio of 5 to 10%: 4 to 8%.

The crosslinking agent is preferably mixed in an amount of 0.01 to 2% based on the total volume of the composition.

The crosslinker is diamine, divinylsulfone, 1,4-butanediol, diglycidyl ether (BDDE) and glutaraldehyde, carbodiimide, hydroxysuccinimide, imidoester, maleimide, haloacetyl , disulfides, hydroazides, and alkoxyamines.

According to another embodiment of the present invention, a method for preparing a natural polymer scaffold for cartilage regeneration or replacement, comprising mixing hyaluronic acid and chondroitin sulfate, is provided.

The hyaluronic acid and chondroitin sulfate are preferably mixed in a weight ratio of 5 to 10%: 4 to 8%.

After the mixing step, it is preferable to further include adding a crosslinking agent.

The crosslinking agent is preferably mixed in an amount of 0.01 to 2% based on the total volume of the composition.

The crosslinker is diamine, divinylsulfone, 1,4-butanediol, diglycidyl ether (BDDE) and glutaraldehyde, carbodiimide, hydroxysuccinimide, imidoester, maleimide, haloacetyl , disulfides, hydroazides, and alkoxyamines.

The cartilage is preferably any one of ear cartilage, nose cartilage, knee cartilage, elbow cartilage or shoulder cartilage.

Example 1. Preparation of Hydrogel Compositions.

Hyaluronic acid having a molecular weight of 800,000 is dissolved in sodium hydroxide, an alkali solution having a pH of 11 to prepare a 5 wt% (w/V) aqueous solution of sodium hyaluronate. Thereafter, a hydrogel composition was prepared by adding 0.3 wt% (w/V) of divinylsulfone as a crosslinking agent.

Example 2.

It proceeded in the same way as in Example 1, but only the component of sodium hyaluronate was adjusted to 6 wt% (w / V).

Example 3.

It proceeded in the same way as in Example 1, but only the component of sodium hyaluronate was adjusted to 7 wt% (w / V).

Example 4.

It proceeded in the same way as in Example 1, but only the component of sodium hyaluronate was adjusted to 8 wt% (w / V).

Example 5.

It proceeded in the same way as in Example 1, but only the component of sodium hyaluronate was adjusted to 9 wt% (w / V).

Example 6.

It proceeded in the same way as in Example 1, but only the component of sodium hyaluronate was adjusted to 10 wt% (w / V).

Example 7.

It proceeded in the same way as in Example 1, but only the component of sodium hyaluronate was adjusted to 12 wt% (w / V).

Example 8.

It proceeded in the same manner as in Example 1, but only the component of divinylsulfone was adjusted to 0.6 wt% (v / W).

Example 9.

It proceeded in the same way as in Example 8, but only the component of sodium hyaluronate was adjusted to 6 wt% (w / V).

Example 10.

It proceeded in the same manner as in Example 8, but only the sodium hyaluronate component was adjusted to 7 wt% (w / V).

Example 11.

It proceeded in the same manner as in Example 8, but only the component of sodium hyaluronate was adjusted to 8 wt% (w / V).

Example 12.

It proceeded in the same way as in Example 8, but only the component of sodium hyaluronate was adjusted to 9 wt% (w / V).

Example 13.

It proceeded in the same way as in Example 8, but only the component of sodium hyaluronate was adjusted to 10 wt% (w / V).

Example 14.

It proceeded in the same way as in Example 8, but only the component of sodium hyaluronate was adjusted to 12 wt% (w / V).

Example 15.

It proceeded in the same manner as in Example 1, but only the component of divinylsulfone was adjusted to 0.8 wt% (w / V).

Example 16.

It proceeded in the same way as in Example 15, but only the component of sodium hyaluronate was adjusted to 6 wt% (w / V).

Example 17.

It proceeded in the same way as in Example 15, but only the component of sodium hyaluronate was adjusted to 7 wt% (w / V).

Example 18.

It proceeded in the same manner as in Example 15, but only the component of sodium hyaluronate was adjusted to 8 wt% (w / V).

Example 19.

It proceeded in the same way as in Example 15, but only the sodium hyaluronate component was adjusted to 9 wt% (w / V).

Example 20.

It proceeded in the same manner as in Example 15, but only the sodium hyaluronate component was adjusted to 10 wt% (w / V).

Example 21.

It proceeded in the same way as in Example 15, but only the component of sodium hyaluronate was adjusted to 12 wt% (w / V).

Example 22. Preparation of hydrogel composition for artificial cartilage

Hyaluronic acid having a molecular weight of 1,200,000 is dissolved in an alkali solution of pH 11 to prepare a 5 wt% (w/V) aqueous solution of hyaluronic acid. When hyaluronic acid is dissolved, 4 wt% (w/v) of chondroitin sulfate is dissolved in an aqueous solution of hyaluronic acid. Thereafter, 0.6 wt% (w/V) of divinylsulfone was added as a crosslinking agent, and the reaction was continued for 5 minutes in an environment at a temperature of 15° C. to prepare a crosslinked gel. The prepared cross-linked gel was poured into a mold and hardened. The cross-linked gel was purified and repeatedly diluted with a phosphate buffer solution to remove the remaining amount of the unreacted cross-linking agent, thereby increasing the purity of the cross-linked gel. Thereafter, a sterilization process was performed at 121° C. for 18 minutes using a high-pressure steam sterilizer under an atmosphere of pH 7 and osmotic pressure of 300 mOsm/kg.

Example 23.

It was carried out in the same manner as in Example 22, but only the sodium hyaluronate component was adjusted to 6 wt% (v / W).

Example 24.

It was carried out in the same manner as in Example 22, but only the sodium hyaluronate component was adjusted to 7 wt% (v / W).

Example 25.

It was carried out in the same manner as in Example 22, but only the sodium hyaluronate component was adjusted to 8 wt% (v / W).

Example 26.

It was carried out in the same manner as in Example 22, but only the sodium hyaluronate component was adjusted to 9 wt% (v / W).

Example 27.

It was carried out in the same manner as in Example 22, but only the sodium hyaluronate component was adjusted to 10 wt% (v / W).

Example 28.

It was carried out in the same manner as in Example 22, but only the sodium hyaluronate component was adjusted to 12 wt% (v / W).

Example 29.

The process was carried out in the same manner as in Example 22, but only the component of chondroitin sulfate was adjusted to 6 wt% (v/W).

Example 30.

The procedure was performed in the same manner as in Example 29, but only the sodium hyaluronate component was adjusted to 6 wt% (v/W).

Example 31.

The procedure was performed in the same manner as in Example 29, but only the sodium hyaluronate component was adjusted to 7 wt% (v/W).

Example 32.

The procedure was performed in the same manner as in Example 29, but only the sodium hyaluronate component was adjusted to 8 wt% (v/W).

Example 33.

It was carried out in the same manner as in Example 29, but only the sodium hyaluronate component was adjusted to 9 wt% (v / W).

Example 34.

It was carried out in the same manner as in Example 29, but only the sodium hyaluronate component was adjusted to 10 wt% (v / W).

Example 35.

It was carried out in the same manner as in Example 29, but only the sodium hyaluronate component was adjusted to 12 wt% (v / W).

Example 36.

The process was carried out in the same manner as in Example 29, but only the chondroitin sulfate component was adjusted to 8 wt% (v/W).

Example 37.

It was carried out in the same manner as in Example 36, but only the sodium hyaluronate component was adjusted to 6 wt% (v / W).

Example 37.

It was carried out in the same manner as in Example 36, but only the sodium hyaluronate component was adjusted to 6 wt% (v / W).

Example 38.

It was carried out in the same manner as in Example 36, but only the sodium hyaluronate component was adjusted to 7 wt% (v / W).

Example 39.

It was carried out in the same manner as in Example 36, but only the sodium hyaluronate component was adjusted to 8 wt% (v / W).

Example 40.

It was carried out in the same manner as in Example 36, but only the sodium hyaluronate component was adjusted to 9 wt% (v / W).

Example 41.

It was carried out in the same manner as in Example 36, but only the sodium hyaluronate component was adjusted to 10 wt% (v / W).

Example 42.

It was carried out in the same manner as in Example 36, but only the sodium hyaluronate component was adjusted to 12 wt% (v / W).

Experimental Example 1. Evaluation of viscosity and elasticity of a hydrogel composition in which hyaluronic acid and divinylsulfone are mixed

The viscosity and elasticity of the hydrogel compositions prepared in Examples 1 to 21 were evaluated.

Table 1 below shows the evaluation of viscosity and elasticity of the hydrogel compositions prepared in Examples 1 to 7.

<Viscosity>

◎: very good viscosity

○: excellent viscosity

△: Weak viscosity

<Elasticity>

◎: very good elasticity

○: excellent elasticity

△: elasticity is weak

ingredient raw material name Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Example 7 (A) component hyaluronic acid 5 6 7 8 9 10 12 (B) component Divinyl sulfones 0.3 0.3 0.3 0.3 0.3 0.3 0.3 viscosity ◎ ◎ ◎ ◎ ◎ ◎ ○ Shout △ △ △ △ △ ○ ○

Table 2 below shows the evaluation of viscosity and elasticity of the hydrogel compositions prepared in Examples 8 to 14.

ingredient raw material name Example 8 Example 9 Example 10 Example 11 Example 12 Example 13 Example 14 (A) component hyaluronic acid 5 6 7 8 9 10 12 (B) component Divinyl sulfones 0.6 0.6 0.6 0.6 0.6 0.6 0.6 viscosity ◎ ◎ ◎ ◎ ◎ ◎ ○ Shout ○ ○ ○ ○ ○ ○ ○

Table 3 below shows the evaluation of viscosity and elasticity of the hydrogel compositions prepared in Examples 15 to 21.

ingredient raw material name Example 15 Example 16 Example 17 Example 18 Example 19 Example 20 Example 21 (A) component hyaluronic acid 5 6 7 8 9 10 12 (B) component Divinyl sulfones 0.8 0.8 0.8 0.8 0.8 0.8 0.8 viscosity ◎ ○ ○ ○ ○ ○ ○ Shout ○ ○ ○ ◎ ◎ ◎ ◎

Referring to Tables 1 to 3, it can be seen that when 0.3% of divinylsulfone was used, the viscous part was excellent, but the elastic part was deteriorated. In the case of using 0.8% of divinylsulfone, it can be seen that the elastic part is excellent, but the viscous part is lowered. Accordingly, when using 0.6% of divinylsulfone, it can be confirmed that the viscous and elastic parts are excellent.

Experimental example 2. Evaluation of viscosity and elasticity of hydrogel composition for artificial cartilage

The viscosity and elasticity of the hydrogel compositions for artificial cartilage prepared in Examples 22 to 42 were evaluated.

Table 4 below shows the evaluation of viscosity and elasticity of the hydrogel compositions prepared in Examples 22 to 28.

ingredient raw material name Example 22 Example 23 Example 24 Example 25 Example 26 Example 27 Example 28 (A) component hyaluronic acid 5 6 7 8 9 10 12 (B) component chondroitin sulfate 4 4 4 4 4 4 4 (C) component Divinyl sulfones 0.6 0.6 0.6 0.6 0.6 0.6 0.6 viscosity ○ ○ ○ ○ ○ ○ △ Shout △ ○ ○ ◎ ◎ ◎ ◎

Table 5 below shows evaluation of the viscosity and elasticity of the hydrogel compositions for artificial cartilage prepared in Examples 29 to 35.

ingredient raw material name Example 29 Example 30 Example 31 Example 32 Example 33 Example 34 Example 35 (A) component hyaluronic acid 5 6 7 8 9 10 12 (B) component chondroitin sulfate 6 6 6 6 6 6 6 (C) component Divinyl sulfones 0.6 0.6 0.6 0.6 0.6 0.6 0.6 viscosity ○ ◎ ◎ ◎ ◎ ○ ○ Shout △ ○ ○ ◎ ◎ ◎ ◎

Table 6 below shows evaluation of the viscosity and elasticity of the hydrogel compositions for artificial cartilage prepared in Examples 36 to 42.

ingredient raw material name Example 36 Example 37 Example 38 Example 39 Example 40 Example 41 Example 42 (A) component hyaluronic acid 5 6 7 8 9 10 12 (B) component chondroitin sulfate 8 8 8 8 8 8 8 (C) component Divinyl sulfones 0.6 0.6 0.6 0.6 0.6 0.6 0.6 viscosity ○ ○ ○ ○ ○ ○ ○ Shout ○ ○ ◎ ◎ ◎ ◎ ◎

Referring to Tables 4 to 6, when comparing chondroitin sulfate, it can be confirmed that the elastic portion increases as the content increases from 4% to 8%. In addition, it can be confirmed that elasticity can be increased while maintaining viscosity by using chondroitin sulfate.

Experimental Example 3. Measurement of physical properties of hydrogel composition for artificial cartilage

In order to confirm the viscoelasticity of the hydrogel composition for artificial cartilage prepared according to the above example, it was analyzed using a rheometer. Specifically, specimens were prepared by dissolving and crosslinking the compositions of the above examples, and then measured using a rheometer device.

Viscoelasticity measurement conditions

(1) Test equipment: Rheometer

(2) Mesuring system : 20.0 mm parallel plate

(3) Measurement temperature: 25℃

(4) Soak Time : 10.0s

Example 30 Example 32 Example 33 Example 34 Example 35 (A) component hyaluronic acid 6 8 9 10 12 (B) component chondroitin sulfate 6 6 6 6 6 (C) component Divinylsulfone 0.6 0.6 0.6 0.6 0.6 Strain(%) 20 20 20 20 20 Measured value (N) 4.63 15.77 14.70 11.73 39.58

Table 7 shows the axial force F(N) value measured by the rheometer, and shows an appropriate value between 10 and 30 when the strain is measured on the basis of 20%. At a value of 30 or more, the elastic part becomes too strong and tends to break, and at a value of 10 or less, the elastic part is weak.

Experimental example 4. Biostability test of hydrogel composition

Using four beagle dogs, the crosslinking gel prepared according to the Example was intradermally administered to each beagle dog. MRI was measured after administration. In addition, during the test period, general symptoms were observed to check for abnormalities, and as a result of volume increase and size measurement, there was no change in volume.

Figure 4 is a graph showing the comparison of volume change for 3 months of the hydrogel composition prepared according to Example 32.

Figure 5 shows the volume change of the hydrogel composition prepared according to Example 32 as an MRI picture.

Referring to Figures 4 and 5, it can be seen that there is no change in volume of the hydrogel composition prepared for 3 months.

In this specification, the present invention has been described with a focus on limited embodiments, but various embodiments are possible within the spirit scope of the present invention. Also, although not described, equivalent means will also be incorporated in the present invention as they are. Therefore, the true scope of protection of the present invention will be defined by the following claims.

Claims (15)

A natural polymer scaffold composition for cartilage regeneration or replacement comprising hyaluronic acid and chondroitin sulfate.
According to claim 1,
The natural polymer scaffold composition for cartilage regeneration or replacement, characterized in that the hyaluronic acid and chondroitin sulfate are crosslinked with each other.
According to claim 2,
The natural polymer scaffold composition for regenerating or replacing cartilage, wherein the hyaluronic acid and chondroitin sulfate are crosslinked through a crosslinking agent.
According to claim 3,
The hyaluronic acid and chondroitin sulfate are crosslinked in a weight ratio of 5 to 10%: 4 to 8%, a natural polymer scaffold composition for regenerating or replacing cartilage.
According to claim 3,
The natural polymer scaffold composition for cartilage regeneration or replacement, wherein the crosslinking agent is mixed in a volume ratio of 0.01 to 2% based on the weight of the composition.
According to claim 3,
The hyaluronic acid, chondroitin sulfate, and crosslinking agent are crosslinked in a weight ratio of 8% to 9%: 6 to 8%,
The natural polymer scaffold composition for regenerating or replacing cartilage, wherein the crosslinking agent is mixed in a volume ratio of 0.5 to 0.7% based on the total weight of the composition.

According to claim 3,
The crosslinker is diamine, divinylsulfone, 1,4-butanediol, diglycidyl ether (BDDE) and glutaraldehyde, carbodiimide, hydroxysuccinimide, imidoester, maleimide, haloacetyl A natural polymer scaffold composition for cartilage regeneration or replacement selected from the group consisting of disulfide, hydroazide, and alkoxyamine.
According to claim 1,
The cartilage is any one of ear cartilage, nose cartilage, knee cartilage, elbow cartilage or shoulder cartilage, a natural polymer scaffold composition for regenerating or replacing cartilage.
A method for preparing a natural polymer scaffold for cartilage regeneration or replacement, comprising mixing hyaluronic acid and chondroitin sulfate.
According to claim 9,
The hyaluronic acid and chondroitin sulfate are mixed in a weight ratio of 5 to 10%: 4 to 8%. A method for manufacturing a natural polymer scaffold for cartilage regeneration or replacement.
According to claim 9,
A method of manufacturing a natural polymer scaffold for cartilage regeneration or replacement, further comprising adding a crosslinking agent after the mixing step.
According to claim 11,
The method of manufacturing a natural polymer scaffold for cartilage regeneration or replacement, wherein the crosslinking agent is mixed in a volume ratio of 0.01 to 2% based on the total weight of the composition.
According to claim 11,
The crosslinker is diamine, divinylsulfone, 1,4-butanediol, diglycidyl ether (BDDE) and glutaraldehyde, carbodiimide, hydroxysuccinimide, imidoester, maleimide, haloacetyl , A method for preparing a natural polymer scaffold for cartilage regeneration or replacement selected from the group consisting of disulfide, hydroazide, and alkoxyamine.
A natural polymer scaffold for cartilage regeneration or replacement made of the composition of any one of claims 1 to 8.
A natural polymer scaffold for cartilage regeneration or replacement produced by the method of any one of claims 9 to 13.

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