A polypeptide material capable of extending drug half-life, and its preparation method and application

Abstract

The present invention relates to a polypeptide material capable of extending the half-life of a drug, a preparation method thereof, and an application thereof. The polypeptide material capable of extending the half-life of a drug comprises a polypeptide drug and an albumin-binding peptide connected to the polypeptide drug, wherein the sequence of the albumin-binding peptide is selected from any one or a combination of at least two of the amino acid sequences shown in SEQ ID NO: 1-6. The present invention creatively develops six new polypeptide sequences, which are connected to polypeptide drugs. These sequences can bind to albumin, utilizing the long half-life of albumin itself to effectively extend the half-life of polypeptide drugs, thereby effectively improving the efficacy of polypeptide drugs. The design of the polypeptide material effectively increases the blood circulation time of polypeptide drugs, providing new ideas, new approaches, and new methods for extending the half-life of polypeptide drugs.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology and relates to a polypeptide material capable of prolonging the half-life of a drug, a preparation method thereof, and an application thereof, and in particular to a polypeptide material capable of prolonging the half-life of triptorelin in the blood, a preparation method thereof, and an application thereof. Background Art

[0002] Peptide drugs are increasingly considered promising drugs due to their high bioactivity and biocompatibility. However, the poor plasma stability and rapid renal clearance of peptide drugs result in a short blood circulation half-life, which limits their clinical application. Many methods have been used clinically to extend the half-life of peptide drugs. (1) Polyethylene glycol (PEG) has been used to modify peptides, such as PEG-modified interferon. (2) Biodegradable polymers as microsphere skeleton materials, such as PLGA microsphere sustained-release carriers, have been widely and successfully used in drug delivery systems for peptide drugs. However, considering safety and tolerability, PEG is not the first choice for injection. In addition, the quality of microsphere preparation is difficult to control. Therefore, there is still a great need to find new materials and solutions to extend the half-life of peptide drugs.

[0003] Nature has provided us with many ideas for developing advanced materials. For example, albumin, abundant in blood and with a long circulatory half-life of 21 days, has emerged as a promising candidate for drug delivery. Antibodies, peptides, and fatty acids can be conjugated to peptide drugs, and binding to albumin can increase their half-life. However, antibody development is expensive and difficult, while fatty acids have low affinity for albumin and poor solubility. Albumin-binding peptides hold promise for extending the half-life of peptide drugs. Summary of the Invention

[0004] In view of the shortcomings of the prior art, the present invention aims to provide a polypeptide material that can prolong the half-life of a drug, a preparation method thereof, and an application thereof, and in particular to provide a polypeptide material that can prolong the half-life of triptorelin in the blood, a preparation method thereof, and an application thereof.

[0005] In order to achieve the purpose of the invention, the present invention adopts the following technical solutions:

[0006] In a first aspect, the present invention provides a polypeptide material that can prolong the half-life of a drug, wherein the polypeptide material that can prolong the half-life of a drug comprises a polypeptide drug and an albumin-binding peptide connected to the polypeptide drug, wherein the sequence of the albumin-binding peptide is selected from any one or a combination of at least two of the amino acid sequences shown in SEQ ID NOs: 1-6.

[0007] SEQ ID NO: 1 is PIKITAI.

[0008] SEQ ID NO: 2 is RRVVGAK.

[0009] SEQ ID NO: 3 is ARIDRPF.

[0010] SEQ ID NO: 4 is KGGVFKA.

[0011] SEQ ID NO: 5 is PIVIKVS.

[0012] SEQ ID NO: 6 is PLKLTIA.

[0013] The present invention creatively develops six new polypeptide sequences and connects them to polypeptide drugs. These sequences can bind to albumin and effectively extend the half-life of polypeptide drugs by utilizing the long half-life of albumin itself, thereby effectively improving the efficacy of polypeptide drugs. The design of this polypeptide material effectively increases the blood circulation time of polypeptide drugs, providing new ideas, new approaches and new methods for extending the half-life of polypeptide drugs.

[0014] Preferably, the albumin binding peptide is directly linked to the polypeptide drug or is linked via a straight chain containing C4-C24 carbons, such as C4, C6, C7, C8, C10, C12, C15, C18, C20, C24, etc.

[0015] The albumin binding peptide and the polypeptide drug in the polypeptide material of the present invention can be directly connected or connected through a carbon chain or heterocarbon chain containing 4-24 carbon atoms, and the latter is more preferred.

[0016] Preferably, the albumin binding peptide and the polypeptide drug are linked via polyethylene glycol.

[0017] Preferably, the structural unit repetition number of the polyethylene glycol is 2-12, such as PEG2, PEG3, PEG4, PEG5, PEG6, PEG7, PEG8, PEG9, PEG10, PEG11, and PEG12.

[0018] Preferably, the polypeptide drug includes triptorelin.

[0019] When the polypeptide drug is triptorelin, the chemical structure of the product obtained by linking it to the albumin-binding peptide represented by SEQ ID NO: 1-2 via PEG8 is as follows:

[0020] a.PIKITAI (Tri-PEG8-ABP1)

[0021]

[0022] b.RRVVGAK(Tri-PEG8-ABP2)

[0023]

[0024] In a second aspect, the present invention provides a method for preparing the polypeptide material capable of prolonging drug half-life according to the first aspect, the preparation method comprising:

[0025] The solid phase synthesis method is adopted to synthesize the albumin binding peptide according to the amino acid sequence, and then connect it with the polypeptide drug to finally synthesize the polypeptide material capable of extending the half-life of the drug.

[0026] Preferably, the synthesized albumin-binding peptide is then linked to the polypeptide drug via polyethylene glycol.

[0027] The polypeptide material involved in the present invention is synthesized by the solid-phase polypeptide synthesis method conventionally used in the art, and the preparation process is simple and easy to operate, and is easy to industrialize and produce.

[0028] In a third aspect, the present invention provides use of the polypeptide material capable of prolonging drug half-life according to the first aspect in the preparation of anti-tumor drugs.

[0029] In a fourth aspect, the present invention provides an anti-tumor combination pharmaceutical composition, wherein the active ingredients of the combination pharmaceutical composition include doxorubicin or a salt thereof and the polypeptide material described in the first aspect.

[0030] The experimental results of the present invention show that compared with free triptorelin, the combination of triptorelin modified with albumin-binding peptide and doxorubicin has more significant anti-tumor efficacy.

[0031] Preferably, the combined pharmaceutical composition further comprises a pharmaceutically acceptable excipient.

[0032] Preferably, the pharmaceutically acceptable excipients include any one or a combination of at least two of a carrier, a diluent, an excipient, a filler, a binder, a wetting agent, a disintegrant, an emulsifier, a solubilizer, a solubilizing agent, an osmotic pressure regulator, a surfactant, a coating material, a colorant, a pH regulator, an antioxidant, an antibacterial agent or a buffer.

[0033] Preferably, the combination pharmaceutical composition is a single compound preparation or a combination of two separate preparations.

[0034] Preferably, the combined pharmaceutical composition is a combination of two separate preparations, and the two separate preparations are administered simultaneously or sequentially.

[0035] The combination pharmaceutical composition may be in the form of a single compound preparation or a combination of two separate preparations; when it is a combination of two separate preparations, the administration method may be simultaneous administration, cross administration or sequential administration.

[0036] Preferably, the preparation is in any pharmaceutically acceptable dosage form, such as tablets, powders, suspensions, granules, capsules, solutions, enemas, emulsions, and the like.

[0037] Compared with the prior art, the present invention has the following beneficial effects:

[0038] The present invention creatively develops six new polypeptide sequences and connects them to polypeptide drugs. These sequences can bind to albumin and effectively extend the half-life of polypeptide drugs by utilizing the long half-life of albumin itself, thereby effectively improving the efficacy of polypeptide drugs. The design of this polypeptide material effectively increases the blood circulation time of polypeptide drugs, providing new ideas, new approaches and new methods for extending the half-life of polypeptide drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Figure 1 This is the mass spectrum of the peptide PIKITA;

[0040] Figure 2 is the mass spectrum of the peptide RRVVGAK;

[0041] Figure 3 is the mass spectrum of the peptide ARIDRPF;

[0042] Figure 4 This is the mass spectrum of the peptide KGGVFKA;

[0043] Figure 5 This is the mass spectrum of the peptide PIVIKVS;

[0044] Figure 6 is the mass spectrum of the peptide PLKLTIA;

[0045] Figure 7 This is a graph showing the protein-specific binding evaluation results of six peptides;

[0046] Figure 8 This is a graph showing the plasma stability evaluation results of six peptides;

[0047] Figure 9 It is the mass spectrum of the peptide materials Tri-PEG8-ABP1 and Tri-PEG8-ABP2;

[0048] Figure 10 is the HPLC profile of Tri-PEG8-ABP1, Tri-PEG8-ABP2, and triptorelin;

[0049] Figure 11 is a graph showing the relationship between the plasma concentrations of Tri-PEG8-ABP1, Tri-PEG8-ABP2, and triptorelin and time;

[0050] Figure 12 Statistical graphs of the cytotoxicity results of Tri-PEG8-ABP1, Tri-PEG8-ABP2, and triptorelin (a is HUVECs cells, b is MDA-MB-231 cells);

[0051] Figure 13 is a statistical graph showing the changes in tumor size over time in each group of mice;

[0052] Figure 14 It is a statistical graph of the changes in weight of mice in each group over time;

[0053] Figure 15 is the statistical graph of physiological and biochemical data of each group of mice;

[0054] Figure 16 It is a schematic diagram of the structure and working principle of the polypeptide material involved in the present invention. DETAILED DESCRIPTION

[0055] The technical solution of the present invention is further described below by way of specific embodiments. It should be understood by those skilled in the art that the embodiments are merely to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0056] The structure of the drug triptorelin involved in the following embodiments is Pyr-HWSY-DTrp-LRPG, which is a self-synthesized product; PEG8 is a product purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.; and the drug DOX is a product of doxorubicin hydrochloride purchased from Beijing Solebau Technology Co., Ltd.

[0057] Example 1

[0058] Preparation of albumin-binding peptides:

[0059] The following six peptides were synthesized according to the standard solid phase peptide synthesis method (SPPS).

[0060] PIKITAI (denoted as ABP1), RRVVGAK (denoted as ABP2), ARIDRPF (denoted as ABP3), KGGVFKA (denoted as ABP4), PIVIKVS (denoted as ABP5), and PLKLTIA (denoted as ABP6).

[0061] Follow these steps:

[0062] (1) Wang resin was swelled with N,N-dimethylformamide;

[0063] (2) Using amino acids with Fmoc protection at the terminal amino group and Boc protection at the side chain amino group as raw materials, first, according to the amino acid sequence of each polypeptide, the first amino acid is added to the carrier resin, coupled with the carrier resin and connected; the Fmoc protecting group on the first amino acid is removed, and the second amino acid is coupled with the first amino acid and connected; until all amino acids in each polypeptide are condensed and the Fmoc protecting group on the last amino acid is removed;

[0064] (3) The resin was shrunk with methanol for 30 min, and then dried. The dried resin was cleaved with a cleavage solution. After the cleavage was completed, the filtrate was filtered and dried with nitrogen. Anhydrous ether was added to precipitate the polypeptide. The polypeptide was then centrifuged and dried to obtain six polypeptides.

[0065] The six peptides were characterized by mass spectrometry. The results were as follows: Figures 1-6 As shown by Figures 1-6 It can be seen from the main peak of the mass spectrum that the molecular weight is consistent with that of the synthesized polypeptide material, thereby inferring that the target molecule has been synthesized.

[0066] Test Example 1

[0067] Determination of binding constant:

[0068] The binding constants of the six peptides described above with human serum albumin were determined using SPR. First, human serum albumin was modified on a bare gold chip with N-hydroxysuccinimide groups. ABP1 to ABP6 were then used as the mobile phase for SPRi analysis. Finally, the binding constants were calculated based on the SPRi curves. The results are shown in Table 1.

[0069] Table 1

[0070] peptides <![CDATA[K D (M)]]> ABP1 <![CDATA[1.0×10 -8 ]]> ABP2 <![CDATA[3.4×10 -8 ]]> ABP3 <![CDATA[2.8×10 -5 ]]> ABP4 <![CDATA[3.4×10 -5 ]]> ABP5 <![CDATA[5.8×10 -6 ]]> ABP6 <![CDATA[1.3×10 -8 ]]>

[0071] From the data in Table 1, we can see that ABPs have smaller K D values, indicating that the OBOC method is very reliable in the screening of targeted peptides. In particular, K D A value of approximately 10 -8 mol / L ABP1, ABP2, and ABP6 showed strong binding ability to human serum albumin. The binding specificity of ABPs to albumin plays an important role in drug delivery.

[0072] Test Example 2

[0073] Specific binding evaluation:

[0074] Procedure: We further explored this specific binding ability using an enzyme-linked immunosorbent assay (ELISA) using fibrinogen and apolipoprotein as controls. These proteins, including fibrinogen, apolipoprotein, and albumin, were coated onto 96-well plates and incubated with ABP before washing with PBS. The plates were then measured using a multimode microplate detection system at a wavelength of 450 nm.

[0075] The results are as follows Figure 7 As shown by Figure 7 ABP1, ABP2, and ABP6 exhibited strong absorbance, indicating strong binding to albumin, consistent with the SPRi experimental results. When bound to fibrinogen and apolipoprotein, ABP1, ABP2, and ABP6 exhibited weak absorbance, similar to that of the blank control. These results validate the reliability of our OBOC peptide library for ABP screening and demonstrate the high specificity of ABP1, ABP2, and ABP6 for albumin.

[0076] Test Example 2

[0077] Plasma stability evaluation:

[0078] Operation process: ABPs were incubated with mouse plasma at 37°C, and the residual ABPs in mouse plasma at different time points were quantitatively monitored using high performance liquid chromatography (HPLC).

[0079] The results are as follows Figure 8 As shown by Figure 8 More than 70% of ABP1 and ABP2 remained in mouse plasma after 12 hours, indicating good plasma stability. This may be due to the binding of ABPs to albumin, which protects ABPs from degradation by plasma enzymes and enhances their plasma stability.

[0080] Example 2

[0081] Preparation of peptide materials:

[0082] The following two peptide materials were synthesized according to the standard solid phase peptide synthesis method (SPPS).

[0083] The product of triptorelin linked to ABP1 via PEG8 (denoted as Tri-PEG8-ABP1) and the product of triptorelin linked to ABP2 via PEG8 (denoted as Tri-PEG8-ABP2). The schematic diagram of its structure and mechanism of action is shown in the figure below. Figure 16 Its chemical structure is shown below:

[0084] Tri-PEG8-ABP1:

[0085]

[0086] Tri-PEG8-ABP2:

[0087]

[0088] Follow these steps:

[0089] (1) Wang resin was swelled with N,N-dimethylformamide;

[0090] (2) Using amino acids with Fmoc-protected terminal amino groups and Boc-protected side chain amino groups as raw materials, first, according to the amino acid sequence of ABP1 and ABP2, the first amino acid is added to the support resin, coupled with the support resin, and connected; the Fmoc protecting group on the first amino acid is removed, and the second amino acid is coupled with the first amino acid and connected; until all amino acids in ABP1 and ABP2 are condensed and the Fmoc protecting group on the last amino acid is removed;

[0091] (3) PEG8 is coupled with ABP1 or ABP2 and connected in the same manner as in (1);

[0092] (4) then undergoing coupling reaction with triptorelin and connecting, the steps are the same as (1);

[0093] (5) The resin was shrunk with methanol for 30 minutes and vacuum dried. The dried resin was cleaved with a cleavage solution. After the cleavage was completed, the filtrate was filtered and evaporated. The polypeptide in the dried product was precipitated with anhydrous ether. The polypeptide was then centrifuged and dried to obtain Tri-PEG8-ABP1 and Tri-PEG8-ABP2.

[0094] The obtained polypeptide material was characterized by mass spectrometry. The mass spectrometry characterization results are as follows: Figure 9 As shown by Figure 9 It can be seen from the mass spectrum that the target molecules were synthesized, indicating that Tri-PEG8-ABP1 and Tri-PEG8-ABP2 were successfully synthesized.

[0095] Test Example 3

[0096] Determination of pharmacokinetic parameters:

[0097] In vivo experiments were performed using female BALB / C mice, each weighing approximately 20 g. All animal experiments were performed according to protocols approved by the Laboratory Animal Ethics Review Committee of the National Center for Nanoscience and Technology.

[0098] Mice were divided into 3 groups, 5 in each group. Blood was collected from the tail vein of mice 0.083, 0.75, 2, 8, 24, and 72 hours after injection of Tri-PEG8-ABP1, Tri-PEG8-ABP2, and triptorelin, respectively. The blood drug concentration was then tested by HPLC. The HPLC graphs are shown in Figure 2. Figure 10 As shown, a curve showing the relationship between blood drug concentration and time is drawn, such as Figure 11 Then, the pharmacokinetic parameters were obtained by fitting the three-compartment model.

[0099] In the three-compartment pharmacokinetic model, three compartments describe the behavior of a drug after administration: the central compartment, representing plasma; the highly perfused compartment, representing organs and tissues highly perfused by blood; and the poorly perfused compartment, representing organs and tissues barely perfused by blood. To simulate the drug's kinetic characteristics, intravenous drug administration was investigated. The processes that cause changes in blood drug concentration include absorption, distribution, and elimination. By fitting the time-drug curves of mice after tail vein injection, a correlation function was introduced and pharmacokinetic parameters were calculated. The results are shown in Table 2.

[0100] Table 2

[0101]

[0102]

[0103] From the data in Table 2, we can see that the distribution half-life (t 1 / 2 α) is shorter than that of triptorelin (6.91 hours). In contrast, the elimination half-life (t 1 / 2The elimination half-lives of Tri-PEG8-ABP1 and Tri-PEG8-ABP2 were significantly prolonged compared with triptorelin, indicating that the albumin binding strategy based on ABPs is effective. The AUC values ​​of Tri-PEG8-ABP1 and Tri-PEG8-ABP2 were 2.6- and 2.7-fold higher than those of triptorelin, respectively. The CL values ​​of Tri-PEG8-ABP1, Tri-PEG8-ABP2, and triptorelin were 0.06, 0.06, and 0.15 mL / h, respectively. The elimination of Tri-PEG8-ABP1 and Tri-PEG8-ABP2 was significantly slower than that of triptorelin. The Vd values ​​of Tri-PEG8-ABP1 and Tri-PEG8-ABP2 were 18.92 and 20.96 mL, respectively, indicating that they are primarily present in the intravascular compartment. Triptorelin may be mainly distributed in the extravascular space or stored in fat or other tissues, with a Vd of 38.53 mL. All these experimental results indicate that the introduction of ABPs effectively prolongs the circulation half-life of triptorelin in the blood of mice.

[0104] Test Example 4

[0105] Cytotoxicity test:

[0106] The cell cultures involved in the experiment were all carried out in DMEM medium containing 10% fetal bovine serum and 1% double antibody at 37°C in a humidified atmosphere containing 5% CO2. HUVECs or MDA-MB-231 cells were seeded in 96-well plates and incubated overnight to allow the cells to adhere. Then, different concentration gradients of Tri-PEG8-ABP1, Tri-PEG8-ABP2 and triptorelin were added to the 96-well plates and incubated for 24 hours. After incubation, the plates were washed twice with PBS, 10% CCK-8 was added to the culture medium, and the plates were incubated in an incubator for 4 hours for testing. The UV-visible absorption spectrum of each well was measured using a microplate reader and the cytotoxicity was calculated. The results are shown in Figure 2. Figure 12 As shown (a is HUVECs cells, b is MDA-MB-231 cells).

[0107] As can be seen from the figure, the experimental results show that Tri-PEG8-ABP1, Tri-PEG8-ABP2 and triptorelin are highly biocompatible with human umbilical vein endothelial cells (HUVECs) and human breast cancer cells (MDA-MB-231), and the cell survival rate at 200 μmol / L is 100%.

[0108] Test Example 5

[0109] Establishment and treatment of mouse subcutaneous tumor model:

[0110] The animals used in the in vivo experiments were BALB / c female nude mice, each weighing approximately 20 g. All animal experiments were performed in accordance with the protocols approved by the Laboratory Animal Ethics Review Committee of the National Center for Nanoscience and Technology. A total of 10 6 MBA-MB-231 cells were mixed with an equal volume of Matrigel and then injected into the flank of mice. 3 BALB / c nude mice were randomly divided into 5 groups, with 6 mice in each group, and the following operations were performed: (1) mice were intravenously injected with PBS; (2) mice were intravenously injected with DOX (the injection dose of DOX was 5 mg / kg); (3) mice were intravenously injected with Tri-PEG8-ABP1+DOX (the injection dose of Tri-PEG8-ABP1 was 10 mg / kg based on triptorelin, and the injection dose of DOX was 5 mg / kg); (4) mice were intravenously injected with Tri-PEG8-ABP2+DOX (the injection dose of Tri-PEG8-ABP2 was 10 mg / kg based on triptorelin, and the injection dose of DOX was 5 mg / kg); (5) mice were intravenously injected with free triptorelin+DOX (the injection dose of triptorelin was 10 mg / kg, and the injection dose of DOX was 5 mg / kg). The mice were injected once every other day for the first two weeks and then observed for one week. The tumor size and body weight of mice in each group were measured and recorded every other day. The statistical graph of the change of tumor size over time in each group of mice is shown in the figure below. Figure 13 As shown in the figure, the tumor volume of the PBS group grew rapidly over time, and the average tumor volume at the end of treatment was as high as 983.8 mm 3 The average tumor volumes of the DOX, Tri-PEG8-ABP1+DOX, Tri-PEG8-ABP2+DOX, and triptorelin+DOX groups were 513.5, 361.4, 400.2, and 450.6 mm, respectively. 3 , which was significantly smaller than that of the PBS group (compared with DOX, ***P<0.001). Tri-PEG8-ABP1+DOX showed the most effective tumor growth inhibition effect, among which the tumor volume of the Tri-PEG8-ABP1+DOX group on day 28 was significantly different from that of the DOX group (*P<0.05). The specific binding of ABPs to albumin effectively prolonged the half-life of triptorelin, thereby enhancing the anti-tumor effect of Tri-PEG-8-ABP1+DOX. The statistical graph of the changes in the weight of mice in each group over time is shown in the figure below. Figure 14 As shown in the figure, there was no significant difference in the body weight of mice between the experimental group and the PBS group, indicating that the injected drug had no obvious toxicity.

[0111] Test Example 6

[0112] Biosafety evaluation:

[0113] Detect the physiological and biochemical data of experimental animals. Collect blood from the mouse's eyeballs and quickly place it in a 1.5mL centrifuge tube (no anticoagulant is required in this process). Let the whole blood stand at room temperature for 60 minutes, centrifuge it at 8000rpm for 15 minutes, use a pipette to draw up the serum and transfer it to a clean centrifuge tube. After taking the serum sample, centrifuge it at 8000rpm for 3 minutes to separate the residual blood cells. Transfer the separated serum to a new centrifuge tube again. Use a fully automatic biochemical analyzer to detect the mouse's complete blood cell count, myocardial enzyme spectrum, blood sugar level and blood lipid level, liver and kidney function, etc. The statistical results are as follows Figure 15 As shown in the figure, there were no significant differences between the PBS, DOX, Tri-PEG8-ABP1+DOX, Tri-PEG8-ABP2+DOX, and Triptorelin+DOX groups, indicating that Tri-PEG8-ABPs do not cause hepatocellular damage. BUN and CREA levels indicate that Tri-PEG8-ABPs do not damage the mouse kidneys. This demonstrates that Tri-PEG8-ABPs possess excellent biocompatibility and biosafety.

[0114] The applicant states that the present invention uses the above-described embodiments to illustrate an anti-tumor polypeptide material capable of extending drug half-life, its preparation method, and its application. However, the present invention is not limited to the above-described embodiments, nor does it necessarily rely on the above-described embodiments for implementation. Those skilled in the art should understand that any improvements to the present invention, equivalent substitutions for raw materials in the present invention's products, addition of auxiliary ingredients, and selection of specific methods, etc., fall within the scope of protection and disclosure of the present invention.

[0115] The preferred embodiments of the present invention are described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the scope of protection of the present invention.

[0116] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any appropriate manner without contradiction. In order to avoid unnecessary repetition, the present invention will not further describe various possible combinations.

Claims

1. A polypeptide material capable of prolonging the half-life of a drug, characterized in that: The polypeptide material capable of extending the half-life of a drug comprises a polypeptide drug and an albumin-binding peptide connected to the polypeptide drug, wherein the sequence of the albumin-binding peptide is selected from any one or a combination of two of the amino acid sequences shown in SEQ ID NOs: 1-2; the albumin-binding peptide is connected to the polypeptide drug via polyethylene glycol.

2. The polypeptide material capable of prolonging drug half-life according to claim 1, characterized in that: The structural unit repeating number of the polyethylene glycol is 2-12.

3. The polypeptide material capable of prolonging drug half-life according to claim 1, characterized in that: The polypeptide drug includes triptorelin.

4. The method for preparing a polypeptide material capable of prolonging drug half-life according to any one of claims 1 to 3, characterized in that: The preparation method comprises: The solid phase synthesis method is adopted to synthesize the albumin binding peptide according to the amino acid sequence, and then the peptide is connected with the peptide drug through polyethylene glycol to finally synthesize the peptide material capable of extending the half-life of the drug.

5. Use of the polypeptide material capable of prolonging drug half-life according to any one of claims 1 to 3 in the preparation of anti-tumor drugs.

6. An anti-tumor combined pharmaceutical composition, characterized in that: The active ingredients of the combined pharmaceutical composition include doxorubicin or its salt and the polypeptide material according to any one of claims 1 to 3.

7. The combined pharmaceutical composition according to claim 6, characterized in that The combined pharmaceutical composition further comprises pharmaceutically acceptable excipients.

8. The combined pharmaceutical composition according to claim 7, characterized in that The pharmaceutically acceptable excipients include any one or a combination of at least two of carriers, diluents, excipients, fillers, binders, wetting agents, disintegrants, emulsifiers, cosolvents, solubilizers, osmotic pressure regulators, surfactants, coating materials, colorants, pH regulators, antioxidants, antibacterial agents or buffers.

9. The combined pharmaceutical composition according to claim 6, characterized in that The combined pharmaceutical composition is a single compound preparation or a combination of two separate preparations.

10. The combined pharmaceutical composition according to claim 9, characterized in that The combined pharmaceutical composition is a combination of two separate preparations, which are administered simultaneously or sequentially.

11. The combined pharmaceutical composition according to claim 9, characterized in that The preparation is in any pharmaceutically acceptable dosage form.

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