A chiral hemostatic polypeptide and its preparation method and application

Abstract

The present invention discloses a chiral hemostatic polypeptide and its preparation method and application. The structural formula of the chiral hemostatic polypeptide is shown in formula (I). The preparation method comprises: activation of resin, coupling of amino acids, excision and precipitation of polypeptide, and separation and purification of polypeptide. The chiral hemostatic polypeptide prepared by the present invention has good biocompatibility, does not cause inflammatory reaction at the wound site, has the function of binding calcium ions, and exhibits excellent effects in hemostasis and bone regeneration. #imgabs0#

Description

Technical Field

[0001] The invention belongs to the technical field of bioengineering and relates to a chiral hemostatic polypeptide and a preparation method and application thereof. Background Art

[0002] Post-extraction bleeding is the most common complication in oral clinical work, mostly caused by local factors. If not treated in time, it can lead to serious complications. Packing is the most common way to treat bleeding in extraction sockets. The rational use of local hemostatic materials to fill extraction sockets is an important measure to treat and prevent post-extraction bleeding. Traditional extraction socket hemostatic materials - iodoform gauze was a commonly used hemostatic material in the early years, but because it is non-degradable, it requires a second surgery to remove it, delaying the healing of the extraction socket, and has gradually been eliminated.

[0003] Commonly used hemostatic materials include gelatin sponge, fibrin glue and medical collagen. Because gelatin sponge is cheap, it is a commonly used hemostatic filling material after tooth extraction in clinical practice. However, gelatin sponge is easy to soften and is not suitable for heavy bleeding in the tooth extraction socket. It is easily washed out by blood and cannot achieve hemostatic effect. Fibrin glue is prepared from human or mammalian plasma. Its main components are mucin and thrombin concentrate. It simulates the body's coagulation process through high concentrations of fibrinogen and coagulation factors to form a fibrin membrane to achieve hemostatic effect. It can also be used for patients with coagulation dysfunction, but because it is a blood product, there is a risk of inducing immune response. Medical collagen is a collagen plug made of collagen, which can expand after absorbing water or blood, and can adhere to the surface of the tissue to achieve a hemostatic effect. In the case of large bleeding, the collagen plug is not easy to soften. Although the above-mentioned hemostatic materials used clinically have a certain hemostatic effect after filling and covering the tooth extraction socket, they are still insufficient in preventing and quickly controlling blood loss.

[0004] With the discovery of research, researchers have achieved certain results in recent years in the use of self-assembling peptide hydrogels in the hemostasis of large tissue and organ injuries, such as liver trauma hemostasis and heart penetration hemostasis. Because it does not require sutures and has good biocompatibility and safety, it has unique advantages as a hemostatic material. The principle of self-assembling peptide hydrogels is that driven by non-covalent weak interactions such as hydrophobic effects, electrostatic effects, and hydrogen bonding, the self-assembling peptides can gel at the bleeding site, thereby significantly reducing blood loss. This self-assembly driven by weak interactions forms a physical barrier into a specific network nanostructure, but the weak interactions between closed bodies make them fragile. At the same time, it is difficult to predict whether self-assembling peptide hydrogels can be used for oral tooth extraction hemostasis.

[0005] The existing hemostatic materials commonly used in clinical extraction sockets, such as gelatin sponges and medical collagen, mostly achieve hemostatic effects by mechanical compression, which allows the materials to swell, adhere, and coagulate blood. Although the above materials have certain hemostatic effects, some hemostatic materials are ineffective for massive bleeding or coagulation disorders, and the hemostatic materials themselves lack the mechanism to interact with the body and cannot achieve rapid hemostatic effects. As for the existing self-assembling polypeptide hydrogels, polypeptides are easily recognized and hydrolyzed by proteases due to their special molecular structure, making it difficult to balance stability and efficacy. Summary of the invention

[0006] The purpose of the present invention is to solve the problems of slow hemostatic speed, poor hemostatic effect, relatively single function, and difficulty in balancing stability and efficacy existing in existing hemostatic materials such as gelatin sponge, fibrin glue, medical collagen, and self-assembling polypeptide hydrogel.

[0007] Based on the above objectives, the present invention provides a chiral hemostatic polypeptide using D-amino acids as raw materials to solve this need in the art.

[0008] In one aspect, the present invention relates to a chiral hemostatic polypeptide, wherein the chiral hemostatic polypeptide has a structural formula as shown in formula (I):

[0009]

[0010] In another aspect, the present invention relates to a method for preparing a chiral hemostatic polypeptide, comprising:

[0011] Resin activation: soak the swollen resin in DMF for 30 min, remove the liquid, wash it twice with DMF and DCM alternately, and then wash it twice with DMF, each washing time is 30 s;

[0012] Amino acid coupling: according to the amino acid sequence of the polypeptide structure shown in formula (I), D-amino acids are activated by HBTU / HOBT and DIEA and then added to the resin, and sequential reactions are carried out from the C-terminus to the N-terminus to obtain a resin containing the polypeptide;

[0013] Removal and precipitation of polypeptide: the polypeptide-containing resin is placed in a cutting solution for 2 to 3 hours, precipitated with ice ether, resuspended in 50% acetonitrile water, and filtered with a 0.45 μM filter membrane to obtain a crude polypeptide; the cutting solution is calculated based on 1 mL of deionized water, and contains 1 mL of deionized water, 17.6 mL of TFA, 0.4 mL of Tips, and 0.7 g of phenol;

[0014] Isolation and purification of polypeptides: The lyophilized crude polypeptide was dissolved in a 6M guanidine hydrochloride aqueous solution, and the crude polypeptide was separated by preparative reverse phase C18 liquid chromatography (HPLC) to collect the main peak product.

[0015] Specifically, in a method for preparing a chiral hemostatic polypeptide provided by the present invention, it comprises:

[0016] (1) Rink Amide MBHA resin was used as the solid phase carrier. The resin was weighed and poured into the reactor. 10 mL of DMF was added to soak and swell the resin. The resin was turned upside down for 30 min. The liquid was drained and the resin was washed twice with DMF and DCM alternately. Finally, the resin was washed twice with DMF, each time for 30 s.

[0017] (2) Elution of Fmoc with DMF containing 20% ​​piperidine twice, for 5 min and 10 min respectively. Wash with DMF once between the two elutions for 30 s, then wash twice with DMF and DCM alternately, and finally wash twice with DMF, each for 30 s. The first D-amino acid dissolved in DMF is activated with HBTU / HOBT and DIEA for 30 s, mixed into the resin, and reacted upside down at room temperature for 30 min. Filter, wash twice with DMF and DCM alternately, and finally wash twice with DMF, each for 30 s. Repeat the above process. According to the amino acid sequence of the polypeptide structure shown in formula (Ⅰ), the reaction is carried out from the C-terminus to the N-terminus to obtain a resin containing a chiral hemostatic polypeptide.

[0018] (3) The resin after the reaction was washed with methanol and DCM four times in sequence, and the resin was dried. The resin was transferred to an acid-base resistant 20 mL glass bottle containing 17.6 mL trifluoroacetic acid, 0.4 mL Tips, 1 mL deionized water, and 0.7 g phenol cutting liquid. The bottle was placed under a magnetic stirrer and stirred for 2 to 3 hours at room temperature at a speed of 550 rpm. After the reaction was completed, the cutting liquid was slowly poured into a 50 mL centrifuge tube filled with ice ether to precipitate a white precipitate. The supernatant was discarded by centrifugation (4 degrees, 4000 rpm, 3 min), and washed with ether three times. Finally, it was resuspended with 50% acetonitrile water, filtered with a 0.45 μM filter membrane, and the liquid was collected in a 50 mL centrifuge tube and quickly frozen in liquid nitrogen to obtain a crude polypeptide.

[0019] (4) The lyophilized crude polypeptide was dissolved in a 6M guanidine hydrochloride aqueous solution, filtered with a 0.22 μM filter membrane, and the crude product was separated using a preparative reverse phase C18 liquid chromatography (HPLC). The main peak product was collected for electrospray mass spectrometry identification, wherein the liquid phase flow rate was 0.1 mL / min, the mobile phase was 50% CAN (containing 1 / 1000 formic acid), and freeze-dried on a freeze dryer to obtain the chiral hemostatic polypeptide, and the polypeptide sample was stored at -20°C.

[0020] In another aspect, the present invention relates to a gel comprising a chiral hemostatic polypeptide and a calcium ion solution.

[0021] Furthermore, in a gel provided by the present invention, every 100L of 1g / L calcium ion solution is mixed with 0.5-10g of the chiral hemostatic polypeptide.

[0022] The present invention modifies and transforms the polypeptide, and uses D-amino acids as raw materials to prepare a chiral hemostatic polypeptide, which is a calcium ion binding peptide. Under the action of calcium ions, the polypeptide sequence self-assembles into nanowires, taking into account stability and efficacy. The gel prepared by a chiral hemostatic polypeptide provided by the present invention has been proven by experiments to exhibit good hemostasis and biocompatibility, does not cause local and systemic inflammatory reactions when used in vivo, and has a short degradation time in the body, and has achieved the effect of promoting hemostasis, wound healing and bone regeneration. Therefore, the present invention further requests protection for the use of the gel prepared by the chiral hemostatic polypeptide provided by the present invention in the preparation of hemostatic materials and in the preparation of materials for promoting bone regeneration. Based on the above applications, the present invention further requests protection for a hemostatic material, a hemostatic composition and a composition for promoting bone regeneration that can be obtained based on the present invention without inventive activities.

[0023] Compared with the prior art, the present invention has the following advantages:

[0024] The gel prepared from the chiral hemostatic polypeptide provided by the present invention has been proved by experiments to exhibit good hemostasis and biocompatibility, does not cause local and systemic inflammatory response when used in vivo, has a short degradation time in the body, and has the effects of promoting hemostasis, wound healing and bone regeneration. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 This is a diagram showing the results of HPLC detection of chiral hemostatic peptides.

[0026] Figure 2 This is the result of electrospray ionization mass spectrometry identification of chiral hemostatic peptides.

[0027] Figure 3 The figure is a diagram of the in vitro coagulation effect of the gel prepared by the chiral hemostatic polypeptide; wherein, Ctrl represents the blank control group, Gelfoam represents the gelatin sponge group, and D represents the chiral hemostatic polypeptide gel group.

[0028] Figure 4 This is a graph showing the changes in the in vitro coagulation index of the gel prepared with the chiral hemostatic polypeptide; wherein Ctrl represents the blank control group, Gelfoam represents the gelatin sponge group, and CaDS represents the chiral hemostatic polypeptide gel group.

[0029] Figure 5 These are the results of subcutaneous HE staining at different time points after subcutaneous transplantation of gelatin sponge or chiral hemostatic polypeptide in rats; Gelfoam represents the gelatin sponge group, and D represents the chiral hemostatic polypeptide gel group.

[0030] Figure 6The results of routine blood tests were shown one day after subcutaneous transplantation of gelatin sponge or chiral hemostatic polypeptide in rats; Gelfoam represents the gelatin sponge group, and D represents the chiral hemostatic polypeptide gel group.

[0031] Figure 7 The results of serum biochemical indexes test on rats after subcutaneous transplantation of gelatin sponge or chiral hemostatic peptides one day after surgery; Figure 7 A is the result of liver function test. Figure 7 B is the result of renal function test. Figure 7 C is a graph showing the results of myocardial enzyme spectrum detection; wherein, Gelfoam represents the gelatin sponge group, and D represents the chiral hemostatic polypeptide gel group.

[0032] Figure 8 These are the evaluation results of the hemostatic efficacy of gelatin sponge or chiral hemostatic polypeptide on rat alveolar sockets; wherein, Ctrl represents the blank control group, Gelfoam represents the gelatin sponge group, and D represents the chiral hemostatic polypeptide gel group.

[0033] Fig. 9 The results are the evaluation results of the effect of gelatin sponge or chiral hemostatic peptide on bone regeneration in rat tooth extraction sockets; Fig. 9 A is a microCT scan. Fig. 9 B is the bone volume ratio (BV / TV), Fig. 9 C is the trabecular thickness (Tb.Th), Fig. 9 D is the trabecular bone space (Tb.sp), Fig. 9 E is the number of trabeculae (Tb.N); where Ctrl represents the blank control group, Gelfoam represents the gelatin sponge group, and D represents the chiral hemostatic polypeptide gel group. DETAILED DESCRIPTION

[0034] The technical solution of the present invention is described below in conjunction with embodiments; however, the present invention is not limited to the following embodiments.

[0035] Example 1

[0036] This example provides the synthesis and preparation of chiral hemostatic polypeptides.

[0037] The HBTU / HOBt method of the HBTU activation / DIEA in-situ neutralization scheme developed for FMOC-chemistry SPPS was used, and D-amino acids were used as raw materials. (rada) 4-gsvlgyiqir (a chiral hemostatic polypeptide with a polypeptide structure and amino acid sequence as shown in formula (I)) was synthesized on a resin (Rink Amide MBHA, substitution rate 0.46 mmol / g) using a CS bio 336X fully automatic peptide synthesizer. The crude product was cleaved and deprotected in a reagent containing 88% TFA, 5% phenol, 5% H2O and 2% TIPS, precipitated with cold ether (Chinese medicine), purified to homogeneity by preparative C18 reversed-phase high performance liquid chromatography (HPLC), and made into a lyophilized powder using a vacuum freeze dryer (cold hydrazine: -80°C, vacuum gauge: 1 Pa), and stored at -20°C for later use.

[0038] Example 2

[0039] This example provides the synthesis and preparation of chiral hemostatic polypeptides.

[0040] (1) Rink Amide MBHA resin was used as the solid phase carrier. The resin was weighed and poured into the reactor. 10 mL of DMF was added to soak and swell the resin. The resin was turned upside down for 30 min. The liquid was drained and the resin was washed twice with DMF and DCM alternately. Finally, the resin was washed twice with DMF, each time for 30 s.

[0041] (2) Elution of Fmoc with DMF containing 20% ​​piperidine twice, for 5 min and 10 min respectively. Wash with DMF once between the two elutions for 30 s, then wash twice with DMF and DCM alternately, and finally wash twice with DMF, each for 30 s. The first D-amino acid dissolved in DMF is activated with HBTU / HOBT and DIEA for 30 s, mixed into the resin, and reacted upside down at room temperature for 30 min. Filter, wash twice with DMF and DCM alternately, and finally wash twice with DMF, each for 30 s. Repeat the above process. According to the amino acid sequence of the polypeptide structure shown in formula (Ⅰ), the reaction is carried out from the C-terminus to the N-terminus to obtain a resin containing a chiral hemostatic polypeptide.

[0042] (3) The resin after the reaction was washed with methanol and DCM four times in sequence, and the resin was dried. The resin was transferred to an acid-base resistant 20 mL glass bottle containing 17.6 mL trifluoroacetic acid, 0.4 mL Tips, 1 mL deionized water, and 0.7 g phenol cutting liquid. The bottle was placed under a magnetic stirrer and stirred for 2 to 3 hours at room temperature at a speed of 550 rpm. After the reaction was completed, the cutting liquid was slowly poured into a 50 mL centrifuge tube filled with ice ether to precipitate a white precipitate. The supernatant was discarded by centrifugation (4 degrees, 4000 rpm, 3 min), and washed with ether three times. Finally, it was resuspended with 50% acetonitrile water, filtered with a 0.45 μM filter membrane, and the liquid was collected in a 50 mL centrifuge tube and quickly frozen in liquid nitrogen to obtain a crude polypeptide.

[0043] (4) The lyophilized crude polypeptide was dissolved in a 6M guanidine hydrochloride aqueous solution, filtered through a 0.22 μM filter membrane, and the crude product was separated using preparative reverse phase C18 liquid chromatography (HPLC). The test results are as follows: Figure 1 The chiral hemostatic polypeptide is obtained by freeze drying in a freeze dryer, and the polypeptide sample is stored at -20°C.

[0044] (5) The main peak products of the liquid phase were collected for electrospray mass spectrometry identification. 20 μL of sample was drawn into the injection bottle and inserted into the tube. The liquid phase flow rate was 0.1 mL / min, the mobile phase was 50% ACN (containing 1 / 1000 formic acid), and the running time was 1 min. The instrument parameters were desolvation gas flow rate (L / Hr): 350, cone gas flow rate (L / hr): 30, low mass resolution (LMResolution): 15, high mass resolution (HM Resolution): 15, ion energy (lon Energy): 0.3, capillary voltage (KV): 3.5, cone voltage (Cone) (V): 30, desolvation gas temperature (°C): 350; m / z range was 400-1600, ionization mode was ES+, and the running time was 1 min. Place the glass bottle containing the sample into the sample tray, name the sample in the sample list interface, set the sample volume to 5μL and the sample location, load the method in the liquid phase method, turn on the liquid phase pump, save the file, and run the sample list. After the program is finished, click Chromatogram in the sample list to export the mass spectrometry data. The test results are as follows: Figure 2 By comparing the mass-to-charge ratio m / z data in the mass spectrum, we calculated whether (MW+Z) / Z was close to the corresponding mass-to-charge ratio in the spectrum, and determined that the molecular weight of the polypeptide prepared by this method was MW: 2759.04 Da, which was consistent with the compound shown in formula (I).

[0045] Example 3

[0046] This example provides an experiment on a gel prepared from a chiral hemostatic polypeptide.

[0047] Weigh 0.5 mg and 10 mg of chiral hemostatic polypeptide powder, dissolve in 100 mL of 1 mg / mL CaCl2 aqueous solution, and dissolve by ultrasonication to prepare chiral hemostatic polypeptide gels with volume fractions of 0.5% and 10%.

[0048] 30 μL of the chiral hemostatic polypeptide gel with a volume fraction of 0.5% and 10% was taken, diluted 100 times, and the absorbance value was detected at 280 nm. The test results are shown in Table 1. The extinction coefficients of the two polypeptides were both 1790, and there was no significant difference in their performance.

[0049] Table 1. Light absorption effect of 0.5% and 10% chiral hemostatic polypeptide gel

[0050] Peptides Volume fraction Absorbance at 280nm Molar concentration (mol / L) D 0.5％ 1.542 8.61 D 10％ 1.344 7.50

[0051] Example 4

[0052] This example provides an in vitro coagulation effect evaluation test of chiral hemostatic polypeptide gel.

[0053] The experiment used 6-8 week old male rats weighing 180-220g. After the rats were anesthetized with sodium pentobarbital, blood was collected from the abdominal vein. A 3.2% sodium citrate solution was prepared and mixed at a ratio of whole blood: sodium citrate = 9:1 to prepare anticoagulated blood. The experiment was divided into a blank control group, a gelatin sponge group, and a chiral hemostatic polypeptide gel group. There was no significant difference in the in vitro coagulation effect of 0.5% and 10% chiral hemostatic polypeptide gels. In the exemplary embodiment, the chiral hemostatic polypeptide gel group selected the chiral hemostatic polypeptide gel used at a volume fraction of 10%. After the anticoagulated blood was recalcified (anticoagulated blood: 0.2M calcium chloride = 9:1), it was slowly dripped on the surface of the hydrogel preheated at 37°C. The culture dishes containing the blood samples were incubated at 37°C for 0.5min, 1.5min, 2.5min, 3.5min, 4.5min, 5min, 5.5min and 6min respectively. At the corresponding time point, 1 mL of deionized water was gently added to release free blood without disturbing the clot. The test results were as follows: Figure 3 The absorbance of the supernatant was measured at a wavelength of 542 nm, and the coagulation results were analyzed by fitting the half-coagulation time (BCI50) through a logarithmic equation. The results are shown in Figure 4 shown.

[0054] Depend on Figure 3The in vitro dynamic whole blood coagulation experiment showed that the chiral hemostatic polypeptide gel group started coagulation faster than the gelatin sponge group and the control group at 0.5 min, achieving a rapid coagulation effect. The gelatin sponge group at 3.5 min and the control group at 4 min were equivalent to the chiral hemostatic polypeptide gel at 0.5 min. Figure 4 It was found that the half-clotting time of the chiral hemostatic polypeptide gel group was 17.1±0.54s, the half-clotting time of the gelatin sponge group was 21.5±0.61s, and the half-clotting time of the control group was 42.3±0.93s.

[0055] Example 5

[0056] This example provides an in vivo inflammatory response evaluation test for chiral hemostatic polypeptide gel.

[0057] The experiment used 6-8 week old male rats weighing 180-220 g. The rats were randomly divided into a gelatin sponge group and a chiral hemostatic polypeptide gel group, with 3 rats in each group. There was no significant difference in the in vivo inflammatory response between 0.5% and 10% chiral hemostatic polypeptide gels. In this exemplary embodiment, the volume fraction of the chiral hemostatic polypeptide gel used in the chiral hemostatic polypeptide gel group was 10%. After sodium pentobarbital anesthesia, 25 mm was filled subcutaneously on the back. 3 The gelatin sponge or 50 μL chiral hemostatic polypeptide gel was injected, and the skin tissue was taken for HE staining after 1 day, 3 days, and 7 days. The results of the HE staining test were as follows: Figure 5 As shown; after 1 day, whole blood and serum were collected for blood routine and serum biochemical index testing. The test results are as follows Figure 6 and Figure 7 shown.

[0058] Depend on Figure 5 It was found that after subcutaneous transplantation of gelatin sponge and chiral hemostatic polypeptide gel, HE staining showed that there was obvious inflammatory cell infiltration around the material in the gelatin sponge group and the chiral hemostatic polypeptide gel group 1 day after transplantation, but the inflammation in the chiral hemostatic polypeptide gel group was relatively mild. Figure 5 It was found that inflammatory cell infiltration in the gelatin sponge group was still very significant 3 to 7 days after surgery, while that in the chiral hemostatic polypeptide gel group was significantly reduced. This indicates that the chiral hemostatic polypeptide gel has an inhibitory effect on inflammation compared with the clinically used gelatin sponge.

[0059] Depend on Figure 6 It can be seen that the results of routine blood tests showed that there was no significant difference between the gelatin sponge group and the chiral hemostatic polypeptide gel group. Figure 7 It can be seen that the results of serum biochemical tests showed that there was no significant difference in liver function, renal function and myocardial enzyme spectrum between the gelatin sponge group and the chiral hemostatic polypeptide gel group. The results showed that the chiral hemostatic polypeptide gel and gelatin sponge had similar biosafety and good biocompatibility.

[0060] Example 6

[0061] This example provides an in vivo hemostasis and bone healing regeneration promotion evaluation test of a chiral hemostatic polypeptide gel.

[0062] The experiment used 6-8 week old male rats weighing 180-220 g. There was no significant difference in the in vivo hemostasis and bone healing regeneration effects of 0.5% and 10% chiral hemostatic polypeptide gel. In the exemplary embodiment, the volume fraction of the chiral hemostatic polypeptide gel used in the chiral hemostatic polypeptide gel group was 10%. Rats were randomly divided into a blank control group, a gelatin sponge group, and a chiral hemostatic polypeptide gel group. After sodium pentobarbital anesthesia, the maxillary right incisor was extracted. The gelatin sponge group filled the extraction socket with 10 mm 3 The chiral hemostatic polypeptide gel group was quickly injected with 50 μL of chiral hemostatic polypeptide gel, and the blank control group was not treated. After complete hemostasis, the bleeding time was recorded, and the results were recorded as follows: Figure 8 One month later, the maxillary tissue of the rats was taken and fixed, and then micro CT scan was performed to observe the healing of the extraction socket. The results are shown in Fig. 9 shown.

[0063] Depend on Figure 8 The maxillary right incisor was extracted, and the amount of bleeding and bleeding time were counted after the operation. The results showed that the hemostatic time of the chiral hemostatic polypeptide gel group was significantly shorter than that of the control group and gelatin sponge group.

[0064] One month after the extraction socket was filled with hemostatic material, the maxillary bone was taken for micro CT analysis of the new bone regeneration in the alveolar socket. The CT imaging results showed that the new bone in the extraction socket of the chiral hemostatic polypeptide gel group was significantly higher than that of the control group and gelatin sponge group ( Fig. 9 A); Analysis of bone mass-related indicators showed that bone volume (BV / TV) and trabecular thickness (Tb.Th) increased significantly, trabecular number (Tb.N) decreased significantly, and trabecular space (Tb.sp) did not change significantly ( Fig. 9 B~ Fig. 9 E), indicating that the chiral hemostatic polypeptide gel can significantly promote the regeneration function of alveolar socket bone, and the chiral hemostatic polypeptide gel can promote the regeneration of new bone in the alveolar socket.

[0065] As described above, the present invention can be well implemented. The above embodiments are only descriptions of the preferred implementation modes of the present invention, and are not intended to limit the scope of the present invention. Without departing from the design spirit of the present invention, various changes and improvements made to the technical solutions of the present invention by ordinary technicians in this field should fall within the protection scope determined by the present invention. Sequence Listing <110> Shaanxi Future Peptide Biotechnology Co., Ltd. <120> A chiral hemostatic polypeptide and its preparation method and application <140> 2022100611283 <141> 2022-01-19 <160> 1 <170> SIPOSequenceListing 1.0 <210> 1 <211> 26 <212> PRT <213> Artificial Sequence <400> 1 Arg Ala Asp Ala Arg Ala Asp Ala Arg Ala Asp Ala Arg Ala Asp Ala 1 5 10 15 Gly Ser Val Leu Gly Tyr Ile Gln Ile Arg 20 25

Claims

1. A gel for use in preparing materials for hemostasis of tooth extraction sockets and promoting new bone regeneration in alveolar sockets, characterized in that: The gel is composed of a chiral hemostatic polypeptide and a calcium ion solution, the amino acid sequence of the chiral hemostatic polypeptide is shown in SEQ ID NO: 1, and the chiral hemostatic polypeptide is composed of D-type amino acids; The gel is prepared by mixing 1 g / L of the calcium ion solution with 0.5-10 g of the chiral hemostatic polypeptide per 100 L.

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