Kidney treatment composition using retina, kidney treatment medical kit including the same, and kidney treatment film including the cured product

Abstract

The present invention relates to a renal treatment composition utilizing the retina, a renal treatment medical kit including the renal treatment composition utilizing the retina, and a renal treatment film including a cured product of the renal treatment composition utilizing the retina.

Description

Technical Field

[0001] This specification claims the benefit of the filing date of Korean Patent Application No. 10-2020-0065439, filed with the Korean Intellectual Property Office on May 29, 2020, and all of its contents are incorporated herein by reference.

[0002] This specification relates to Peritoneum a kidney treatment using Complex , a medical kit for kidney treatment including Peritoneum a kidney treatment using Complex , and a film for kidney treatment including a hardened product of Peritoneum a kidney treatment using Complex .

Background Art

[0003] Recently, with the development of medicine, the death rate due to acute complications of diabetes has decreased, but the macrovascular and microvascular complications belonging to the chronic complications of diabetes are rather increasing. In particular, diabetic kidney disease, which is one of the microvascular complications of the glomerulus, is the most main cause of end-stage renal disease (ESRD) and accounts for the highest frequency among the mortality rates due to diabetic complications.

[0004] As general pathological findings of such diabetic kidney disease, hypertrophy of glomeruli and renal tubules due to hyperglycemia, proliferation of mesangial cells, and accumulation of mesangial matrix appear. Due to the continuous progression of such a phenomenon, glomerulosclerosis occurs, and eventually, kidney function disorders such as renal failure are induced.

[0005] In the case of kidney diseases, the symptoms appear slowly and it is difficult to recognize that it is a chronic kidney disease, and the treatment period is often missed. In order to prevent chronic kidney disease, it is essential to prevent it through periodic check-ups. At present, when it has already progressed to chronic kidney disease, there is no other treatment method other than dialysis or transplantation.

Prior Art Documents

Patent Document

[0006]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0007] The present invention aims to provide a kidney treatment using Peritoneum which can assist in the recovery of the kidneys of patients with kidney diseases, Complex the above - mentioned Peritoneum a kidney treatment using Complex a medical kit for kidney treatment including Peritoneum a kidney treatment using Complex and a film for kidney treatment including a hardened product of Complex . Specifically, the present invention provides a kidney treatment for patients with kidney diseases whose glomerular filtration rate has decreased to 60 / ml / min / 1.73m2 or less, or patients with kidney diseases diagnosed with albuminuria of 30mg / gCr or more to recover their damaged kidneys.

[0008] One embodiment of the present invention provides Miniaturized peritoneum a kidney treatment using Peritoneum omentum tissue extract and a biocompatible adhesive. Complex

[0009] Another embodiment of the present invention provides a medical kit for kidney treatment in which the above - mentioned Peritoneum is filled in a syringe for human injection. Complex

[0010] Still another embodiment of the present invention provides a medical kit for kidney treatment in which the above - mentioned Peritoneum is filled in a syringe for human injection. Complex ​​​

Advantages of the Invention

[0011] The Peritoneum used for kidney treatment Complex and / or the film for kidney treatment has the advantage of being able to prevent the decline of kidney function or restore kidney function through minimal surgery.

[0012] In addition, the Peritoneum used for kidney treatment Complex and / or the film for kidney treatment uses autologous tissue, so when applied to the human body, it can provide an environment suitable for cell survival, delay fibrosis (renal fibrosis), which is a pathological feature of chronic renal failure, by substances secreted from these, and suppress necrosis of kidney cells, and has the advantage of being able to enhance cell activity in damaged tissues.

Brief Description of the Drawings

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Mode for Carrying Out the Invention

[0021] In the specification of the present application, when a certain part "includes" a certain component, this means that, unless otherwise stated to the contrary, it does not exclude other components, but may further include other components.

[0022] In the specification of the present application, when a certain member is located "above" another member, this includes not only the case where a certain member is in contact with another member, but also the case where there is another member between the two members.

[0023] Hereinafter, the present invention will be described in detail.

[0024] One embodiment of the present invention is Miniaturized peritoneum (omentum) tissue extract; and a biological adhesive; including Peritoneum for kidney treatment using Complex to provide.

[0025] According to one embodiment of the present invention, the Miniaturized peritoneum tissue extract may be obtained by pulverizing the extracted Peritoneum (omentum) tissue.

[0026] According to one embodiment of the present invention, the micronized Peritoneum formed (omentum) tissue extract isPeritoneum The source stromal cells, Peritoneum may contain the derived extracellular matrix.

[0027] According to one embodiment of the present invention, the Peritoneum source stromal cells Peritoneum may be extracted from, and may contain mesothelial cells, Mesenchymal Stem Cells (MSCs), and immune cells. The Peritoneum source stromal cells play a role in promoting the differentiation of kidney cells on damaged kidney tissue and helping to differentiate into kidney cells that can replace damaged kidney cells.

[0028] According to one embodiment of the present invention, the Peritoneum derived extracellular matrix Peritoneum may be extracted from, and this may be decellularized. The Peritoneum derived extracellular matrix can secrete various substances that improve cell activity on damaged kidney tissue, thereby preventing the recovery of damaged kidney tissue and further damage to the kidney. Specifically, the Peritoneum derived extracellular matrix has biochemical factors necessary for kidney cells to grow and differentiate, and can provide a physical environment that can be fixed after the Peritoneum source stromal cells differentiate into kidney cells.

[0029] According to one embodiment of the present invention, the Miniaturized peritoneum derived tissue extract Peritoneum may be derived from autologous or allogeneic

[0030] According to one embodiment of the present invention, the Miniaturized peritoneum derived tissue extract

[0031] According to one embodiment of the present invention, the Miniaturized peritoneum derived tissue extract PeritoneumIt may be derived from. Preferably, the Peritoneum source tissue may also be derived from autologous Peritoneum . Specifically, according to one embodiment of the present invention, the Miniaturized peritoneum source tissue extract may be derived from autologous greater omentum.

[0032] According to one embodiment of the present invention, the Miniaturized peritoneum source tissue extract may contain source tissue particles having an average particle size of 5 μm or more and 200 μm or less. Peritoneum The average particle size of the source tissue particles may be measured using a laser extinction method using a particle analyzer, or may be measured using a scanning electron microscope. Alternatively, it is also possible to determine whether it corresponds to the average particle size by whether it passes through a filter having a pore diameter of 5 μm or more and 200 μm or less. Peritoneum

[0033] According to one embodiment of the present invention, the Miniaturized peritoneum source tissue extract may be obtained by extracting or Peritoneum or Peritoneum crushing and filtering the tissue. Specifically, the Miniaturized peritoneum source tissue extract may be obtained by the steps of mixing the extracted or Peritoneum or Peritoneum tissue with physiological saline and then crushing and filtering with a first filter having a pore diameter of 1 mm to 3 mm to obtain a first filtrate; crushing and filtering the first filtrate with a second filter having a pore diameter of 400 μm to 800 μm to obtain a second filtrate; and crushing and filtering the second filtrate with a third filter having a pore diameter of 5 μm to 200 μm to obtain a third filtrate. The Miniaturized peritoneum source tissue extract may contain the third filtrate. Specifically, the Miniaturized peritoneum source tissue extract may contain the precipitated lower layer portion after centrifuging the third filtrate.

[0034] According to one embodiment of the present invention, the step of obtaining the first filtrate is to extract the Peritoneum or Peritoneum After mixing the tissue with physiological saline, it may be pulverized and filtered through a first filter having a pore diameter of 2 mm to 3 mm, and further pulverized and filtered through an additional first filter having a pore diameter of 1 mm to 1.5 mm to obtain the first filtrate.

[0035] According to one embodiment of the present invention, the filter may be a syringe filter made of stainless steel. After attaching syringes to both ends of the filter for the pulverization and filtration, by utilizing the piston movement of the syringe, the object may be pulverized and filtered by passing it through the filter 1 to 30 times, specifically 10 to 15 times.

[0036] By the pulverization, Peritoneum or Peritoneum the tissue is pulverized into fine particles, which can be used as it is or the required cells can be extracted and used. However, Peritoneum or Peritoneum the method of pulverizing the tissue is not limited to this, and various methods known in the art can be utilized.

[0037] According to one embodiment of the present invention, the Miniaturized peritoneum content of the tissue extract from which it is derived may be 40% by volume or more and 90% by volume or less, specifically 50% by volume or more and 80% by volume or less. When the Miniaturized peritoneum content of the tissue extract from which it is derived is less than 40% by volume, although the content of the biocompatible adhesive is high and it is easy to maintain a solid form such as a film, the activity for kidney treatment is low, and effective regeneration of kidney cells may not occur. Further, when the Miniaturized peritoneum content of the tissue extract from which it is derived exceeds 90% by volume, it is difficult to maintain a solid form, and a problem may occur that it is difficult to apply to a damaged kidney.

[0038] According to one embodiment of the present invention, the biological adhesive may contain at least one selected from the group consisting of fibrin glue, collagen, gelatin, cyanoacrylate polymer, polyurethane polymer, polyglycolic acid polymer, hydrogel, hyaluronic acid, alginic acid, Pluronic (registered trademark) F-127, and cellulose polymer. Specifically, the biological adhesive may be fibrin glue and / or gelatin, and more specifically, it may be fibrin glue.

[0039] According to one embodiment of the present invention, when the biological adhesive is fibrin glue, the Peritoneum for kidney treatment using Complex may be composed of a first liquid containing fibrinogen and a second liquid containing thrombin. Two-component complex Or, the Peritoneum for kidney treatment using Complex may be composed of a first liquid containing the Miniaturized peritoneum tissue extract and thrombin and a second liquid containing fibrinogen. Two-component complex According to one embodiment of the present invention, the biological adhesive can utilize fibrin glue composed of fibrinogen and thrombin, which can ensure higher viscosity than a hyaluronic acid adhesive or a collagen adhesive. Therefore, the customized dermal regeneration film has the advantage of excellent adhesion to the affected area and, thus, can maintain high strength.

[0040] According to one embodiment of the present invention, the Peritoneum for kidney treatment using Complex is of a two-component type. After the first liquid and the second liquid are sequentially applied onto the damaged kidney tissue, they react to form a kidney treatment film on the kidney tissue in the human body.

[0041] According to one embodiment of the present invention, the fibrin matrix through the reaction of fibrinogen and thrombin in the first liquid and the second liquid serves to fix the Peritoneum derived tissue.

[0042] According to one embodiment of the present invention, the concentration of fibrinogen in the first liquid or the second liquid may be 4 mg / ml to 90 mg / ml. Further, according to one embodiment of the present invention, the concentration of thrombin in the first liquid or the second liquid may be 50 IU / ml to 500 IU / ml.

[0043] When the concentrations of the fibrinogen and the thrombin are within the above ranges, an appropriate hardening rate can be ensured and the distribution of the Miniaturized peritoneum (omentum) tissue extract can be maintained uniformly in the fibrin matrix. Thereby, the cell distribution in the kidney treatment film formed by being injected onto the damaged kidney cells or in the patch-type kidney treatment film can be maintained uniformly, and the cell differentiation ability can be effectively achieved on the damaged kidney tissue. Further, when the concentrations of the fibrinogen and the thrombin are within the above ranges, the form of the film can be well maintained, and there is an advantage that it can be applied to the affected part while maintaining an appropriate hardness.

[0044] According to one embodiment of the present invention, when the first liquid contains fibrinogen, the first liquid may further contain aprotinin. The aprotinin is an inhibitor of proteolytic enzymes secreted from the pancreas and is a polypeptide composed of a total of 58 amino acids. It is mainly extracted from bovine lungs and is known to inhibit the decomposition of fibrin in blood and have a hemostatic effect.

[0045] According to one embodiment of the present invention, the aprotinin may be contained at 900 KIU to 1,100 KIU (kininogen Inactivator Unit), specifically 1000 KIU, per 1 ml of the first liquid.

[0046] According to an embodiment of the present invention, when the second liquid contains thrombin, the second liquid may be one in which thrombin is dispersed in a calcium chloride solution. Specifically, the second liquid may contain 40 IU to 250 IU of thrombin and 5 mg to 6.5 mg of calcium chloride per 1 ml.

[0047] According to an embodiment of the present invention, the Peritoneum for kidney treatment using Complex may further contain water as a solvent. Specifically, the Peritoneum for kidney treatment using Complex may further contain physiological saline. The solvent may be a part of the solvent used when Miniaturized peritoneum the tissue extract is obtained by Peritoneum grinding, or may be a solvent containing the solvent of the biological conjugate.

[0048] According to an embodiment of the present invention, the solvents of the first liquid and the second liquid may be water, specifically, physiological saline. Also, fibrinogen in the first liquid and thrombin in the second liquid can be obtained through a common fibrin glue kit.

[0049] According to an embodiment of the present invention, the Peritoneum for kidney treatment using Complex can be injected into the kidney, specifically, the renal capsule, in a non-solidified state, and formed into a film in the renal capsule by the hardening of the biological adhesive. Or, the Peritoneum for kidney treatment using Complex can be solidified into a film and applied to the kidney by a method of inserting it under the renal capsule of the kidney.

[0050] Specifically, according to an embodiment of the present invention, the Peritoneum for kidney treatment using Complex is Two-componentThe first liquid and the second liquid are sequentially injected into the kidney to induce the reaction between the first liquid and the second liquid, so that a film-type kidney treatment film can be formed in the kidney. Specifically, thrombin in the second liquid and fibrinogen in the first liquid can react to form a fibrin network, which Miniaturized peritoneum plays a role in ensuring that the tissue extract is sufficiently fixed.

[0051] Since the reaction between the first liquid and the second liquid is completed within 5 minutes, there is an advantage that the first liquid and the second liquid can be sequentially applied onto the damaged kidney tissue, specifically, under the kidney capsule, using a syringe for human injection, so that it can be quickly hardened. Also, the Peritoneum kidney treatment using Complex has the advantage that a kidney treatment film adapted to the damaged kidney tissue can be immediately manufactured using a (3D) printer at the operation site and transplanted into the kidney.

[0052] According to an embodiment of the present invention, the Peritoneum kidney treatment using Complex may have physical properties suitable for passing through a 25G - 30G injection needle. Specifically, the Peritoneum kidney treatment using Complex contains a viscosity and particles suitable for passing through a 25G - 30G injection needle, and can be injected more precisely or can be precisely controlled in shape during the manufacture of the kidney treatment film. More specifically, the Peritoneum kidney treatment using Complex has the advantage that it can pass through a 30G fine injection needle and can be injected more precisely when injecting into the kidney.

[0053] Another embodiment of the present invention provides a kidney treatment medical kit in which the Peritoneum kidney treatment using Complex is filled in a syringe for human injection. As described above, the Peritoneum kidney treatment using ComplexAfter being injected into the kidney through the syringe for human injection in a non-solidified state, it hardens, forms a film on the damaged kidney tissue, and can assist in the regeneration of damaged kidney cells.

[0054] According to an embodiment of the present invention, the medical kit for kidney treatment may include a first syringe for human injection filled with the first liquid and a second syringe for human injection filled with the second liquid. As described above, after injecting and applying the first liquid onto the damaged kidney tissue using the first syringe for human injection, the second liquid is applied onto the first liquid using the second syringe for human injection, so that a film for kidney treatment can be formed on the damaged kidney tissue. That is, when using the medical kit for kidney treatment, there is an advantage that the operation can be performed while minimizing the wetting during the operation of a kidney disease patient.

[0055] Another embodiment of the present invention provides a film for kidney treatment, which includes a hardened product of the Peritoneum used for kidney treatment Complex .

[0056] According to an embodiment of the present invention, the film for kidney treatment may be rod-shaped, mesh-shaped, or cylindrical. The film for kidney treatment can be manufactured in an appropriate size and shape according to the pattern of the damaged kidney tissue and transplanted.

[0057] According to an embodiment of the present invention, the film for kidney treatment can be manufactured by hardening the Peritoneum used for kidney treatment Complex . Alternatively, the film for kidney treatment can be manufactured by applying the Peritoneum used for kidney treatment Complex onto a biodegradable polymer base and hardening it. The biodegradable polymer base may be a porous patch or a scaffold.

[0058] According to an embodiment of the present invention, the patch-type kidney treatment film can induce a reaction by applying the second liquid on a layer formed by applying the first liquid, and can be manufactured using a bioprinter machine known in the art. Specifically, a kidney treatment film in a form adapted to the affected area can be manufactured using a Dr.INVIVO series bioprinter machine available from Rocket Healthcare.

[0059] According to an embodiment of the present invention, the thickness of the patch-type kidney treatment film may be 100 μm or more and 1,000 μm or less.

[0060] According to an embodiment of the present invention, the stiffness of the kidney treatment film may be 0.5 kPa or more and 12 kPa or less. The kidney treatment film can be adjusted to satisfy the stiffness range by adjusting the content of the bioadhesive applied to the kidney treatment. The kidney treatment film is adjusted within the stiffness range, which is easy to handle for insertion into kidney tissue. Also, it can maintain an appropriate strength within the kidney tissue and affect cell growth, differentiation, and migration through the signal transduction system between cells and the surrounding extracellular matrix, helping to recover damaged kidney tissue. Complex To satisfy the stiffness range, the content of the bioadhesive applied to the kidney treatment can be adjusted. The kidney treatment film is adjusted within the stiffness range, which is easy to handle for insertion into kidney tissue. Also, it can maintain an appropriate strength within the kidney tissue and affect cell growth, differentiation, and migration through the signal transduction system between cells and the surrounding extracellular matrix, helping to recover damaged kidney tissue.

[0061] Hereinafter, the present invention will be specifically described in detail with reference to examples. However, the examples according to the present invention can be modified into various other forms, and the scope of the present invention should not be construed as being limited to the examples described below. The examples in the specification of the present application are provided to more fully explain the present invention to those having average knowledge in the art.

Example

[0062] (Production Example)

[0063] (1) Miniaturized peritoneum Obtaining tissue extract

[0064] After anesthetizing the experimental mice, the Peritoneum (specifically, the greater omentum) was extracted. A syringe containing the greater omentum and a new syringe were attached to both injection ports of a connector containing a stainless-steel syringe filter with a pore diameter of 2.4 mm, and the greater omentum was passed through the stainless-steel syringe filter 11 times by piston movement. Furthermore, using a stainless-steel syringe filter with a pore diameter of 1.2 mm, the greater omentum was passed through the stainless-steel syringe filter 11 times by piston movement to perform primary grinding. Then, a syringe containing the ground primary filtrate and a new syringe were attached to both injection ports of a connector containing an in-stainless-steel syringe filter with a pore diameter of 600 μm, and the primary filtrate was passed through 11 times by piston movement to perform secondary grinding. Finally, a syringe containing the ground secondary filtrate and a new syringe were attached to both injection ports of a connector containing an in-stainless-steel syringe filter with a pore diameter of 200 μm, and the secondary filtrate was passed through 11 times by piston movement to perform tertiary grinding. The resulting mixture containing tissue particles with a diameter of 200 μm or less was washed with the same amount of physiological saline, Peritoneum and a tissue extract was obtained. Miniaturized peritoneum

[0065] (2) Peritoneum was used for the production of Complex kidney treatment

[0066] The obtained Miniaturized peritoneum tissue extract and 1 ml of aprotinin solution mixed with 90 mg / ml of fibrinogen were mixed at a volume ratio of 4:1 using a mix syringe to produce the first solution. At this time, the final concentration of fibrinogen in the first solution was 18 mg / ml.

[0067] Furthermore, a second solution of calcium chloride solution in which the same volume of thrombin as the produced first solution was dispersed was prepared. At this time, the concentration of thrombin in the second solution was approximately 500 IU / ml.

[0068] (Experimental Example 1) Production of Film for Kidney Treatment

[0069] The above-mentioned Peritoneum was used for kidney treatment Complex Prior to manufacturing the film for kidney treatment using, the viscosity depending on the concentration of Peritoneum used for kidney treatment Complex was confirmed.

[0070] In the first liquid of the above production example, Miniaturized peritoneum the content of the tissue extract was adjusted to 20% by volume, 50% by volume, and 80% by volume respectively, and it was discharged using a 3D bioprinter (Dr.INVIVO) available through Rocket Healthcare, and the results were confirmed.

[0071] Figure 1 shows the discharge result of the film for kidney treatment using the 3D bioprinter according to Experimental Example 1. Complex Specifically, in Figure 1, Miniaturized peritoneum when the content of the tissue extract was 20% by volume, it was confirmed that the viscosity was too low and the discharged material could not form a shape and was scattered. Miniaturized peritoneum When the content of the tissue extract was 50% by volume or more, it was confirmed that it had a viscosity suitable for manufacturing a film in a desired form such as a mesh type.

[0072] Figure 2 shows the production result of the film for kidney treatment using the 3D bioprinter according to Experimental Example 1. Specifically, Figure 2 shows that after discharging the first liquid containing 80% by volume of Miniaturized peritoneum tissue extract in a mesh shape using a 25G or 27G nozzle, the second liquid was applied and cured. According to Figure 2, Miniaturized peritoneum when the first liquid containing 80% by volume of tissue extract was used, it was confirmed that a mesh-type film with a good form could be manufactured.

[0073] Also, the obtained Miniaturized peritoneum tissue extract was mixed with fibrin glue, discharged into a rod-shaped mold and cured, and then its handleability and whether the form could be maintained were confirmed.

[0074] Figure 3 shows the manufacturing results of the rod-shaped kidney treatment film according to Experimental Example 1. Specifically, according to Figure 3, it was found that the higher the content of fibrin glue, the more advantageous it is in terms of handleability and film shape maintenance. However, Miniaturized peritoneum when the content of the tissue extract that can assist in the regeneration of kidney cells is low, the therapeutic effect for kidney treatment may decrease. Therefore, at a content of 50 vol% or more Miniaturized peritoneum even when the tissue extract is included, minimal handleability and form maintenance are possible. Therefore, at a content of 50 vol% or more Miniaturized peritoneum when the tissue extract is included Complex it was determined that it is appropriate to use it.

[0075] Figure 4 shows various shapes of the kidney treatment film manufactured as in Example 1 and examples of its application. As can be confirmed from Figure 4, the kidney treatment film according to Example 1 can be manufactured and applied in various shapes as needed to fit the damaged site of the kidney.

[0076] (Experimental Example 2) Peritoneum for kidney treatment using Complex Confirmation of the effect of using for kidney treatment

[0077] One ureter of the experimental mouse was blocked to create a UUO model (unilateral ureteral obstruction model) to exhibit histological changes such as chronic renal insufficiency. In such an experiment, the experiment was conducted in each of the following three types, and the results were observed.

[0078] (case1) Injection for kidney treatment using a syringe Complex of

[0079] The manufactured kidney treatment ComplexIt was injected under the renal capsule using a syringe to confirm the therapeutic effect on the kidney. At this time, the first liquid in the production example was injected under the capsule of the damaged kidney region, and subsequently, the second liquid was applied so that it could be solidified into a film shape under the renal capsule.

[0080] (case2) Insertion of the manufactured kidney treatment film

[0081] Manufactured for kidney treatment Complex To output it, first, using the hot melt function of a 3D bioprinter (Rocket Healthcare, Dr.INVIVO), a frame of the polymer material PCL was output in a rod shape of 30 mm × 5 mm × 0.8 mm (width × length × height). Then, using the dispenser of the 3D bioprinter, after applying the first liquid to the PCL frame, the second liquid was used to cure it to manufacture a kidney treatment film. The manufactured kidney treatment film was inserted under the capsule of the damaged kidney region.

[0082] (case3) Insertion of the manufactured kidney treatment film and kidney treatment using a syringe Complex Injection

[0083] The kidney treatment film manufactured in the same manner as the film production method in case2 Complex was manufactured by applying the first liquid to a size suitable for the affected area using a 3D bioprinter (Rocket Healthcare, Dr.INVIVO) and then curing it using the second liquid to manufacture a kidney treatment film. The manufactured kidney treatment film was inserted under the capsule of the damaged kidney region. Then, the first liquid in the production example was injected into the cortical region under the capsule where the kidney treatment film was inserted, and subsequently, the second liquid was applied and cured.

[0084] Figure 5 shows the production of the UUO model according to Experimental Example 2 and the application of the kidney treatment Complex Specifically, the arrow in Figure 5 is the ureter, which was closed to produce the UUO model, and the kidney treatment film and kidney treatment were applied to the kidney region where sclerosis occurred according to case3 Complexwhich shows that injection has been performed.

[0085] Figure 6 shows the staining results of kidney tissues according to Experimental Example 2. Specifically, Figure 6 shows kidney tissues in a state where the UUO model is not applied (normal), kidney tissues in a state where no separate measures are taken after the UUO model is applied (-), kidney tissues in a state where the measures of case 1 are taken (injection), kidney tissues in a state where the measures of case 2 are taken (film), and kidney tissues in a state where the measures of case 3 are taken (injection / film). Each of them was fixed with a 4% paraformaldehyde solution to produce a paraffin block, which was sectioned to a thickness of about 4 μm and stained with H&E (hematoxylin-eosin).

[0086] In Figure 6, the dotted circular region indicates the glomerulus region. And the arrow 1 is the region of the glomerulus, the arrow 2 is the region of tubule necrosis, the arrow 3 is the region of interstitial fibrosis, and the arrow 4 indicates the region of immune cell infiltration.

[0087] Specifically, according to the results of Figure 6, compared with the case where no measures are taken after applying the UUO model, in all cases of case 1 to case 3 according to the experimental example, it was confirmed that the structure of the glomerulus and the cells in the glomerulus maintained a normal form. In particular, when no measures are taken after applying the UUO model, it was confirmed that tubule necrosis (arrow 2) appears, and when the measures according to Example 2 are taken, it was confirmed that almost no tubule necrosis is found. Thus, when Peritoneum used for kidney treatment Complex is applied, it was confirmed that the necrosis / death of nephrons such as glomeruli or tubules in the kidney injury model is delayed, and as a result, the recovery of damaged cells is achieved.

[0088] Figures 7 and 8 show the results of quantifying the number of glomeruli in the results of Experimental Example 2. Figure 7 shows the kidney tissue (normal) in a state where the UUO model is not applied, the kidney tissue (injury) in a state where no separate measure is taken after the UUO model is applied, and the kidney tissue (treatment) in a state where the measure of case 1 is taken. After staining the kidney tissue as described above, it shows the number of glomeruli and cell nuclei. Specifically, the left column of Figure 7 shows the glomeruli pointed out, and the black region in the right column indicates the cell nuclei. Further, Figure 8 quantitatively shows the results of Figure 7 in a graph.

[0089] According to Figures 7 and 8, the number of glomeruli was calculated at 8 locations in the 3 mm 2 region. As a result, in the normal tissue (normal), about 26 glomeruli were measured per 3 mm 2 . In the kidney tissue (injury) in a state where no separate measure is taken after the UUO model is applied, only about 5 glomeruli were measured per 3 mm 2 . In contrast, in the kidney tissue (treatment) with the measure according to Experimental Example 2, about 13 glomeruli were measured per 3 mm 2 . From such results, when using the Peritoneum for kidney treatment according to the present invention Complex is applied, it was confirmed that necrosis of glomeruli in the UUO model is prevented, or damage to kidney cells is prevented.

Claims

1. A composite for kidney treatment using the peritoneum, comprising a micronized tissue derived from the omentum and a biocompatible adhesive.

2. The composite for kidney treatment using the peritoneum according to Claim 1, wherein the micronized tissue derived from the peritoneum contains peritoneum-derived stromal cells and peritoneum-derived extracellular matrix.

3. The composite for kidney treatment using the peritoneum according to Claim 1, wherein the micronized tissue derived from the peritoneum is derived from autologous or allogeneic peritoneum.

4. The composite for kidney treatment using the peritoneum according to Claim 1, wherein the micronized tissue derived from the peritoneum is derived from the greater omentum.

5. The composite for kidney treatment using the peritoneum according to Claim 1, wherein the micronized tissue derived from the peritoneum contains peritoneum-derived tissue particles having an average particle size of 5 μm or more and 200 μm or less.

6. The composite for kidney treatment using the peritoneum according to Claim 1, wherein the content of the micronized tissue derived from the peritoneum is 40% by volume or more and 90% by volume or less.

7.

8. The biocompatible adhesive contains at least one selected from the group consisting of fibrin glue, collagen, gelatin, cyanoacrylate polymer, polyurethane polymer, polyglycolic acid polymer, hydrogel, hyaluronic acid, alginic acid, Pluronic (registered trademark) F-127, and cellulose polymer. The composite for kidney treatment using the peritoneum according to Claim 1.

9. The biocompatible adhesive is fibrin glue comprising fibrinogen and thrombin,

10. The composite for kidney treatment using the peritoneum

11. is composed of a first liquid containing the micronized tissue derived from the omentum and fibrinogen and a second liquid containing thrombin, or

12. A two-component composite composed of a first liquid containing the micronized tissue derived from the omentum and thrombin and a second liquid containing fibrinogen. The composite for kidney treatment using the peritoneum according to Claim 1.

13.

14. A medical kit for kidney treatment, wherein the composite for kidney treatment using the peritoneum according to Claim 1 is filled in a syringe for human injection.

15.

16. A kidney treatment film containing a hardened product of the composite for kidney treatment using the peritoneum according to Claim 1.

17. ​ The kidney treatment film according to claim 10, characterized in that it is rod-shaped, mesh-shaped, or cylindrical.

12. The kidney treatment film according to claim 10, characterized in that the stiffness of the kidney treatment film is 0.5 kPa or more and 12 kPa or less.

Images