A kind of polypeptide material for driving solution and its preparation method and application in preparing spherical propellant

Abstract

The application discloses a kind of polypeptide materials for driving solution and its preparation method and its application in the preparation of spherical propellant, belong to pharmaceutical technical field, the polypeptide material has temperature sensitivity, can be self-assembled into nanoparticle when temperature is lower than 84 DEG C, can be disassembled into polypeptide molecule soluble in water when temperature is higher than 84 DEG C, when the polypeptide material is applied in the preparation of spherical propellant, first nitrocellulose or absorbent drug and ethyl acetate are prepared dispersed phase, then the above-mentioned polypeptide material is prepared continuous phase, dispersed phase is added into continuous phase, and high molecular solution is dispersed into small droplet by high-speed stirring effect, the polypeptide material is self-assembled into nanoparticle, is coated on the surface of droplet, avoids droplet stickiness, when temperature rises to 84 DEG C-98 DEG C, nanoparticle disassembles into polypeptide molecule soluble in water by washing removal to prepare formed spherical propellant, improve the preparation efficiency of spherical propellant.

Description

Technical Field

[0001] This invention belongs to the field of spherical drug preparation technology, specifically, it relates to a polypeptide material for dissolving and its preparation method and its application in the preparation of spherical propellants. Background Technology

[0002] Spherical propellants are a typical type of propellant. Spherical propellants usually refer to granular propellants with a near-spherical shape and nitrocellulose as the main component. Compared with the manufacturing technology of granular propellants of other shapes, spherical propellants are formed by the surface tension of liquid substances, which greatly simplifies the preparation process of propellants.

[0003] The preparation methods for spherical propellants can be broadly classified into two types: internal dissolution and external dissolution. The principle of the internal dissolution method for preparing spherical propellants is to suspend raw materials such as nitrocellulose or absorbent in water, then add a solvent. Under heating and stirring conditions, the material is dissolved into a polymer solution with a certain viscosity. Through high-speed stirring, the polymer solution is dispersed into fine droplets. The droplets are immiscible with water. When droplets with large specific surface areas collide with each other, the droplets will adhere and tend to spontaneously aggregate into large particles.

[0004] To prevent droplet aggregation, a gelatin solution is typically added to the water as a protective colloid during the dissolution process after spherical formation. The gelatin adsorbs onto the surface of the spherical droplets, forming a protective film that prevents the droplets from sticking together when they collide. As the temperature of the dissolution process increases, the solvent inside the droplets is released, and the droplet viscosity gradually increases. After reaching a certain level, aggregation no longer occurs, resulting in nitrocellulose particles, thus preparing spherical propellants.

[0005] In the internal dissolution method for preparing spherical propellants, nitrocellulose droplets are dissolved in water to remove the solvent. To prevent droplet aggregation, a gelatin solution is added to the water as a protective colloid. However, for large nitrocellulose droplets, the protective effect of the gelatin solution deteriorates. Furthermore, as the dissolution stage progresses and the temperature rises from 64℃ to above 84℃, the surface tension of the gelatin solution decreases significantly with increasing temperature. This results in poor coating of the nitrocellulose droplets in the later dissolution stages, making them prone to aggregation and affecting the size uniformity and sphericity of the nitrocellulose particles. Additionally, gelatin is insoluble in water; when immersed, it absorbs 5-10 times its weight in water and swells and softens. If heated, it dissolves into a colloid. In actual production, a large amount of gelatin needs to be dissolved. The gelatin solution requires high temperature and prolonged stirring during preparation, and the solution will gelatinize when the concentration exceeds 2%. Moreover, the gelatin solution requires multiple washings after dissolution to remove it, reducing the efficiency of spherical propellant preparation.

[0006] In view of the above problems, the present invention provides a polypeptide material that is soluble in water at room temperature, which can improve the preparation efficiency when preparing spherical propellants to solve the above problems. Summary of the Invention

[0007] The purpose of this section is to outline some aspects of embodiments of the present invention and to briefly describe some preferred embodiments. Simplifications or omissions may be made in this section, as well as in the abstract and title of this application, to avoid obscuring the purpose of these documents; however, such simplifications or omissions should not be construed as limiting the scope of the invention.

[0008] To solve the above problems, the present invention adopts the following technical solution.

[0009] A polypeptide material for dissolving scavenging, with the following structural formula: Figure 1 As shown.

[0010] Preferably, the above-mentioned polypeptide material is temperature sensitive, capable of self-assembling into nanoparticles at temperatures below 84°C and disassembling into water-soluble polypeptide molecules at temperatures above 84°C.

[0011] Preferably, the aforementioned polypeptide material comprises a group of peptides and a hydrophobic peptide connected in sequence, wherein,

[0012] The assembled peptide sequence is any one of SEQ ID NO.1-SEQ ID NO.5, and the hydrophobic peptide sequence is any one of SEQ ID NO.6-SEQ ID NO.8; wherein;

[0013] SEQ ID NO.1: (VPGFG)5;

[0014] SEQ ID NO.2: (VPGFG) 10 ;

[0015] SEQ ID NO.3: PSFCFKFEPCCPSFCFKFEP;

[0016] SEQ ID NO.4: WCFFAFAFCN WCFFAFAFCN;

[0017] SEQ ID NO.5: WCFFAFAFCNFFAFAFCN;

[0018] SEQ ID NO.6: FWYFFWYF;

[0019] SEQ ID NO.7: FWYYYWF;

[0020] SEQ ID NO.8: FFWYYFF.

[0021] Preferably, in the above-mentioned polypeptide material, the secondary structure of the assembled peptide molecule presents a mixed structure of α-helix and β-sheet. In a solution at a temperature below 84°C, the polypeptide material molecules for dissolving are assembled into nanoparticles by relying on the hydrogen bond network formed by the secondary structures of β-sheet and α-helix between the assembled peptides and the π-π stacking hydrophobic interaction between the hydrophobic peptides.

[0022] Preferably, in the above-mentioned polypeptide material, the spatial structure of the nanoparticle is any one or a combination of at least two of α-helices, β-sheets, and π-π stacking.

[0023] Preferably, in the above-mentioned polypeptide material, the dissolution-removing polypeptide material has a group peptide sequence as shown in SEQ ID NO.5 and a hydrophobic peptide sequence as shown in SEQ ID NO.8.

[0024] Another aspect of the present invention provides a method for preparing the above-mentioned dissolution-removing polypeptide material, comprising the following steps:

[0025] Step 1: Remove the Fmoc protecting group at the N-terminus of phenylalanine Wang resin with a modification density of 0.35 mM using a mixed solution of hexahydropyridine and N,N-dimethylformamide in a volume ratio of 1:4 to obtain phenylalanine Wang resin.

[0026] Step 2: Add coupling agent to phenylalanine and benzotriazole-N,N,N',N'-tetramethylurea hexafluorophosphate and stir to dissolve; transfer the solution to a peptide synthesis tube and react for 45 min; at this time, phenylalanine has been coupled to the phenylalanine Wang resin in Step 1 to obtain phenylalanine-phenylalanine;

[0027] Step 3: Repeat Step 2, replacing phenylalanine in Step 2 with tyrosine, tryptophan, phenylalanine, phenylalanine, asparagine, cysteine, phenylalanine, alanine, phenylalanine, alanine, phenylalanine, phenylalanine, asparagine, cysteine, phenylalanine, alanine, phenylalanine, phenylalanine, phenylalanine, cysteine ​​and tryptophan in sequence, and forming peptide resin through condensation reaction;

[0028] Step 4: Wash the peptide resin into the peptide synthesis tube with N,N-dimethylformamide. Remove the synthesized peptide from the resin with a trifluoroacetic acid solution containing 2.5% water and 2.5% triisopropylsilane, while removing the side chain protection of the amino acids. After removing the trifluoroacetic acid, precipitate the crude peptide product with anhydrous diethyl ether, wash and dry to obtain the peptide material for dissolution.

[0029] Preferably, in the above preparation method, the coupling agent is a mixed solution of N-methylmorpholine and N,N-dimethylformamide in a volume ratio of 5:95.

[0030] In another aspect, the present invention provides a technical solution for the application of the above-mentioned dissolution-removing polypeptide material in the preparation of spherical propellants, as detailed below.

[0031] Step 1: Prepare the dispersed phase and the continuous phase separately;

[0032] Ethyl acetate was chosen as the solvent for the dispersed phase, and nitrocellulose was added to prepare a nitrocellulose solution.

[0033] The continuous phase is made of water as a solvent, and the above-mentioned dissolution-removing polypeptide material is added.

[0034] Step 2: Add the dispersed phase to the continuous phase under continuous stirring and stir. The dispersed phase is dispersed into fine droplets and then dissolved to obtain the spherical propellant.

[0035] Preferably, in the above applications, the dissolution process is as follows:

[0036] When the temperature is 64~78℃, the polypeptide material assembles into nanoparticles on the surface of the droplets by hydrogen bonds, van der Waals forces and π-π interactions. The nanoparticles are amphiphilic, hydrophobic inside and hydrophilic outside, and form a protective film on the surface of the nitrocellulose droplets. When the droplets collide with each other, the protective film prevents the droplets from sticking together and keeps the droplets spherical.

[0037] When the temperature rises to 78~84℃, the ethyl acetate solvent inside the droplet diffuses outward through the gaps between the nanoparticles or evaporates to complete the dissolution, and the droplet gradually hardens and solidifies to form a spherical propellant.

[0038] When the temperature continues to rise to 84~98℃, the polypeptide nanoparticles disassemble into water-soluble polypeptide molecules, which are then removed from the surface of the spherical propellant by washing. The dissolution process is then complete, and the spherical propellant is obtained.

[0039] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0040] The polypeptide material in this invention can self-assemble into nanoparticles at temperatures below 84°C and deassemble into water-soluble polypeptide molecules at temperatures above 84°C. In the first stage of dissolution (dissolution temperature 64-78°C) and the second stage (dissolution temperature 78-84°C), the polypeptide material assembles into nanoparticles with high specific surface tension. These nanoparticles can coat the surface of nitrocellulose droplets, preventing droplets from sticking together and providing excellent protection. In the third stage of dissolution (dissolution temperature 84°C-98°C), the nanoparticles deassemble into water-soluble polypeptide molecules, which can be removed from the surface of the nitrocellulose particles without repeated washing. The nitrocellulose particles dissolved using this polypeptide material exhibit good sphericity and size uniformity, thereby improving the efficiency of spherical drug preparation. Attached Figure Description

[0041] Figure 1 This is the molecular structural formula of the polypeptide material in this invention;

[0042] Figure 2 The results of dynamic light scattering of the polypeptide material in this invention at 25℃, 55℃, 75℃ and 84℃ are shown in the figure.

[0043] Figure 3 This is a transmission electron microscope image of the polypeptide material in this invention at 100 nm.

[0044] Figure 4 This is a structural diagram of the spherical propellant in this invention under a microscope with a DIV of 1.01 mm.

[0045] Figure 5 This is a diagram showing the size distribution of the spherical propellant in this invention;

[0046] Figure 6 This is a sphericity distribution diagram of the spherical propellant in this invention;

[0047] Figure 7 This is a graph showing the detection results of residual polypeptide material after one washing of the spherical propellant in this invention. Detailed Implementation

[0048] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, the specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings.

[0049] Many specific details are set forth in the following description in order to provide a full understanding of the invention. However, the invention may also be practiced in other ways different from those described herein, and those skilled in the art can make similar extensions without departing from the spirit of the invention. Therefore, the invention is not limited to the specific embodiments disclosed below.

[0050] Secondly, the term "one embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The phrase "in one embodiment" appearing in different places throughout this specification does not necessarily refer to the same embodiment, nor is it a single or selective embodiment that mutually excludes other embodiments. The present invention provides the following embodiments.

[0051] Example 1

[0052] This embodiment provides a polypeptide material for dissolving water. This polypeptide material is temperature-sensitive; it can self-assemble into nanoparticles at temperatures below 84°C and disassemble into water-soluble polypeptide molecules at temperatures above 84°C. The molecular structure of this polypeptide material is as follows: Figure 1 As shown.

[0053] The polypeptide material in this embodiment is composed of sequentially linked histoid peptides and hydrophobic peptides.

[0054] The assembled peptide sequence is any one of SEQ ID NO.1-SEQ ID NO.5, wherein the sequences of SEQ ID NO.1-SEQ ID NO.5 are as follows:

[0055] SEQ ID NO.1: (VPGFG)5;

[0056] in,

[0057] The number 5 represents the pentapeptide (VPGFG) repeated 5 times; that is, the sequence of SEQ ID NO.1 is: VPGFGVPGFGVPGFGVPGFGVPGFG;

[0058] SEQ ID NO.2: (VPGFG) 10 ;

[0059] in,

[0060] 10 represents the pentapeptide (VPGFG) repeated 10 times; that is, the sequence of SEQ ID NO.2 is: VPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFG;

[0061] SEQ ID NO.3: PSFCFKFEPCCPSFCFKFEP;

[0062] SEQ ID NO.4: WCFFAFAFCNWCFFAFAFCN;

[0063] SEQ ID NO. 5: WCFFAFAFCNFFAFAFCN.

[0064] The hydrophobic peptide sequence is any one of SEQ ID NO. 6-SEQ ID NO. 8, wherein the sequences of SEQ ID NO. 6-SEQ ID NO. 8 are as follows:

[0065] SEQ ID NO.6: FWYFFWYF;

[0066] SEQ ID NO.7: FWYYYWF;

[0067] SEQ ID NO.8: FFWYYFF.

[0068] In the above sequence,

[0069] The sequence SEQ ID NO.1, VPGFG corresponds to valine, proline, glycine, phenylalanine, and glycine, respectively;

[0070] The sequence SEQ ID NO.2, VPGFG corresponds to valine, proline, glycine, phenylalanine, and glycine, respectively;

[0071] The sequence PSFCFKFEPCCPSFCFKFEP in SEQ ID NO.3 corresponds to proline, serine, phenylalanine, cysteine, phenylalanine, lysine, phenylalanine, glutamic acid-proline, cysteine, cysteine, proline, serine, phenylalanine, cysteine, phenylalanine, lysine, phenylalanine, glutamic acid, and proline, respectively.

[0072] The sequence SEQ ID NO.4, WCFFAFAFCN, corresponds to tryptophan, cysteine, phenylalanine, phenylalanine, alanine, phenylalanine, alanine, phenylalanine, cysteine, asparagine, tryptophan, cysteine, phenylalanine, phenylalanine, alanine, phenylalanine, alanine, phenylalanine, cysteine, asparagine, respectively.

[0073] The sequence SEQ ID NO.5, WCFFAFAFCNFFAFAFCN, corresponds to tryptophan, cysteine, phenylalanine, phenylalanine, alanine, phenylalanine, alanine, phenylalanine, cysteine, asparagine, phenylalanine, phenylalanine, alanine, phenylalanine, alanine, phenylalanine, cysteine, asparagine, respectively.

[0074] The sequence SEQ ID NO.6, FWYFFWYF, corresponds to phenylalanine, tryptophan, tyrosine, phenylalanine, phenylalanine, tryptophan, tyrosine, and phenylalanine, respectively.

[0075] The sequence SEQ ID NO.7, FWYYYWF, corresponds to phenylalanine, tryptophan, tyrosine, tyrosine, tyrosine, tryptophan, and phenylalanine, respectively.

[0076] The sequence SEQ ID NO.8, FFWYYFF, corresponds to phenylalanine, phenylalanine, tryptophan, tyrosine, tyrosine, phenylalanine, and phenylalanine, respectively.

[0077] In this embodiment, the secondary structure of the assembled peptide molecules in the polypeptide material exhibits a mixed structure of α-helices and β-sheets. Here, α-helix refers to the helical structure of the peptide chain, and β-sheet refers to the folding of the peptide bond plane into a serrated shape. In aqueous solutions at temperatures below 84°C, the solubilizing polypeptide material in this embodiment exhibits temperature responsiveness due to the hydrogen bond network formed by the secondary structures of β-sheets and α-helices between the assembled peptides and the π-π stacking hydrophobic interactions between the hydrophobic peptides. Here, π-π stacking refers to the stacking structure in the aromatic ring. The polypeptide material molecules in this embodiment can be assembled into nanoparticles, referred to as nanoparticles.

[0078] When the temperature rises above 84°C, the hydrogen bond network between the assembled peptides is disrupted, and the assembled structure changes from an ordered mixture of β-sheets and α-helices to a disordered random coil structure. At the same time, the thermal energy provided by the high temperature also disturbs the relatively stable π-π stacking between aromatic rings in the hydrophobic peptides, causing the assembled structure of the polypeptide material in this embodiment to become loose and disintegrate, and the nanoparticles disassemble into water-soluble polypeptide molecules.

[0079] In this embodiment, the above-mentioned polypeptide material is synthesized by solid-phase synthesis. The polypeptide material self-assembles in a buffer solution at room temperature to form nanoparticles. The spatial structure of the nanoparticles is any one or a combination of at least two of α-helices, β-sheets, and π-π stacks. For example, it can be a combination of α-helices, β-sheets, π-π stacks, or a combination of α-helices and π-π stacks, a combination of β-sheets and π-π stacks, or a combination of α-helices, β-sheets, and π-π stacks. In this embodiment, the polypeptide material is preferably a combination of α-helices, β-sheets, and π-π stacks.

[0080] Specifically, the steps for synthesizing polypeptide materials using the solid-phase synthesis method described above are as follows.

[0081] In this embodiment, the synthesis of the dissolving polypeptide material is exemplified by a combination of a grouped peptide sequence of SEQ ID NO.5 and a hydrophobic peptide sequence of SEQ ID NO.8 (WCFFAFAFCNFFAFAFCNFFWYYFF).

[0082] The amino acids corresponding to WCFFAFAFCNFFAFAFCNFFWYYFF are as follows.

[0083] W-Tryptophan-C-Cysteine-F-Phenylalanine-F-Phenylalanine-A-Alanine-F-Phenylalanine-A-Alanine-F-Phenylalanine-C-Cysteine-N-Asparagine-F-Phenylalanine-F-Alanine-F-Phenylalanine-A-Alanine-F-Phenylalanine-C-Cysteine-N-Asparagine-F-Phenylalanine-F-Phenylalanine-W-Tryptophan-Y-Tyrosine-Y-Tyrosine-F-Phenylalanine-F-Phenylalanine.

[0084] A phenylalanine Wang resin with a modification density of 0.35 mM was selected (phenylalanine Wang resin refers to resin in which the I-terminus of isoleucine is fixed on the resin and the N-terminus is protected by a Fmoc protecting group). The Fmoc protection at the N-terminus was removed using a mixed solution of hexahydropyridine and N,N-dimethylformamide in a volume ratio of 1:4, and the success of deprotection was verified by the ninhydrin test. The second amino acid, phenylalanine, and benzotriazole-N,N,N',N'-tetramethylurea hexafluorophosphate were weighed out at 10 times the molar mass of phenylalanine. Then, a coupling agent (a mixed solution of N-methylmorpholine and N,N-dimethylformamide in a volume ratio of 5:95) was added and stirred to dissolve the phenylalanine. The solution was transferred to a peptide synthesis tube and reacted for 45 min. At this point, phenylalanine had been coupled to the phenylalanine Wang resin, resulting in phenylalanine-phenylalanine.

[0085] Next, the third amino acid, tyrosine, was coupled. As above, tyrosine and benzotriazole-N,N,N',N'-tetramethylurea hexafluorophosphate were weighed in at 10 times the molar mass of phenylalanine. Then, a coupling agent (a mixture of N-methylmorpholine and N,N-dimethylformamide in a volume ratio of 5:95) was added and stirred until dissolved. The solution was transferred to a peptide synthesis tube and reacted for 45 min. At this point, tyrosine had been coupled to the phenylalanine-phenylalanine Wang resin, yielding tyrosine-phenylalanine-phenylalanine.

[0086] Repeat the above steps to link all the remaining amino acids (tyrosine, tryptophan, phenylalanine, phenylalanine, asparagine, cysteine, phenylalanine, alanine, phenylalanine, alanine, phenylalanine, phenylalanine, asparagine, cysteine, phenylalanine, alanine, phenylalanine, phenylalanine, phenylalanine, cysteine, tryptophan) to form a peptide resin through a condensation reaction.

[0087] The peptide resin was washed into the peptide synthesis tube using N,N-dimethylformamide. The synthesized peptide was removed from the resin using a trifluoroacetic acid solution containing 2.5% water and 2.5% triisopropylsilane, simultaneously removing the side chain protection of the amino acids. The trifluoroacetic acid was removed by rotary evaporation. The crude peptide product was precipitated with anhydrous diethyl ether, washed, and dried to obtain a cationic therapeutic peptide, an assembled peptide, and a β-D-glucopyranose conjugate, which is the dissolution-removing peptide material in this embodiment. Sequencing showed that the peptide material in this embodiment has the sequence WCFFAFAFCNFFAFAFCNFFWYYFF, with its hermetically structured peptide sequence shown in SEQ ID NO.5 and its hydrophobic peptide sequence shown in SEQ ID NO.8.

[0088] In this embodiment, the polypeptide material self-assembles in a buffer solution at room temperature to form nanoparticles. The buffer solution can be any one of water, sulfate aqueous solution, phosphate buffer solution, Tris-HCl buffer solution or HEPES buffer solution.

[0089] In this embodiment, the buffer solution is an aqueous sulfate solution with a concentration of 10 mM to 20 mM.

[0090] In addition, the concentration of the peptide material in the buffer (i.e., sulfate aqueous solution) is 50~200μM, for example, it can be 50μM, 55μM, 60μM, 65μM, 70μM, 75μM, 80μM, 85μM, 90μM, 95μM, 100μM, 105μM, 110μM, 115μM, 120μM, 125μM, 130μM, 135μM, 140μM, 145μM, 150μM, 155μM, 160μM, 165μM, 170μM, 175μM, 180μM, 185μM, 190μM, 195μM, 200μM;

[0091] In this embodiment, the buffer concentration is 80 μM.

[0092] In this embodiment, the size and morphology of the polypeptide materials prepared above were verified at different temperatures, as detailed below.

[0093] The prepared polypeptide materials were dissolved in buffer solutions at 25°C, 55°C, 75°C, and 84°C, i.e., sulfate aqueous solutions (hereinafter referred to as sulfate solutions). The particle size distribution of the dissolution-removing polypeptide nanomaterials in the sulfate solution buffer system was detected by dynamic light scattering (DLS) as a function of temperature. The results are as follows: Figure 2 As shown in the figure, the peptide material can assemble at 25℃, 55℃, and 75℃, and is stably distributed at around 200nm at 25℃. As the temperature increases to 55℃, the nanoparticle size stabilizes at around 100nm, and at 75℃, it stabilizes at around 40nm. This demonstrates that in a buffer system below 84℃, the peptide material assembles into stable nanoparticles. As the buffer system temperature increases to 84℃, the nanoparticles disassemble, which is represented by a straight line in the DLS data plot, indicating that at temperatures above or equal to 84℃, the nanoparticles can disassemble into water-soluble peptide molecules.

[0094] Furthermore, the morphology of the dissolving polypeptide in sulfate buffer at 60°C was observed using transmission electron microscopy (lanthanum hexaboride transmission electron microscope, Tecnai G2 20 S-TWIN(T-20), FEI Corporation, USA). The resulting morphology image of the polypeptide nanoparticles is shown below. Figure 3 As shown in the figure, at a temperature of 60℃, the polypeptide material assembles into nanoparticles in the range of 40-100 nm, proving that the polypeptide material can assemble into nanoparticles at temperatures below 84℃.

[0095] Example 2

[0096] This embodiment provides a technical solution for the application of the dissolution-removing polypeptide material prepared above in the preparation of spherical propellants.

[0097] The dissolution-removing peptide material prepared in Example 1 can achieve good sphericity and size uniformity in the preparation of spherical propellants, and can be removed from the surface of nitrocellulose particles without multiple washings after dissolution. Specifically, a dispersed phase and a continuous phase are prepared separately. Ethyl acetate is used as the solvent for the dispersed phase, and nitrocellulose is added to prepare a nitrocellulose solution. The dissolution-removing peptide material prepared in Example 1 is added to the continuous phase using water as the solvent. Then, the dispersed phase is added to the continuous phase under continuous stirring and high-speed stirring is used to disperse the dispersed phase into fine droplets. Then, dissolution is carried out. At the beginning of dissolution, the temperature is 64~78℃. The peptide material assembles into nanoparticles on the surface of the spherical material, i.e., nitrocellulose, through hydrogen bonds, van der Waals forces, and π-π interactions. The nanoparticles are amphiphilic, hydrophobic inside and hydrophilic outside, and can coat the surface of the nitrocellulose droplets to form a protective film with high surface tension. When the droplets collide with each other, the protective film prevents the droplets from sticking together, so that they maintain their spherical shape and do not aggregate into large irregularly shaped aggregates. As the temperature rises to 78–84 °C, the nanoparticles retain their morphology. The ethyl acetate solvent inside the nanoparticles diffuses outward through the gaps between the nanoparticles or evaporates, completing the dissolution process. The propellant nanoparticles gradually harden and solidify. In the final stage of dissolution, the temperature continues to rise to 84–98 °C. The polypeptide nanoparticles disassemble and reassemble into water-soluble polypeptide molecules, which are removed from the surface of the nanoparticles without repeated washing. After dissolution, spherical propellants with good sphericity and size uniformity are obtained. The size of these spherical propellants is 130–164 μm.

[0098] Preferably, during dissolution, the concentration of the added peptide material is no more than 500 μM, for example, it can be 100 μM, 200 μM, 300 μM, 400 μM, or 500 μM. In this embodiment, the concentration of the added peptide material is 300 μM.

[0099] To further illustrate the technical solution of the dissolution-removing polypeptide material in the preparation of spherical propellants in this embodiment, the following specific application steps are given in this embodiment.

[0100] Material:

[0101] Nitrocellulose;

[0102] Ethyl acetate solvent; purchased from Sinopharm Chemical Reagents (Beijing) Co., Ltd.

[0103] The preparation process of the spherical propellant includes the following steps:

[0104] Step 1: Raw material preparation and solution preparation

[0105] Dispersed phase preparation: At room temperature (20-30℃), use ethyl acetate as the solvent to prepare a 15-20 wt% nitrocellulose solution. The typical concentration range is 15-20 wt%, which means that 15-20 g of nitrocellulose is dissolved in 100 g of solvent.

[0106] Continuous phase preparation: 0.5-2.0 wt% of the dissolving polypeptide material prepared in Example 1 was added to water. Its function is to reduce the oil-water interfacial tension, stabilize emulsion droplets, and prevent them from coalescing.

[0107] Step 2: Solvent Dissolving Preparation Process

[0108] The continuous phase is added to a three-necked flask equipped with a mechanical stirrer, thermometer, and reflux condenser. Stirring is started and heating is initiated, maintaining the continuous phase temperature at 64–78°C. Using a constant and moderate stirring speed (300–600 rpm), the insulated dispersed phase solution is slowly and dropwise added to the continuous phase via a constant pressure funnel or syringe pump for 10–30 minutes. During this process, under heating and stirring conditions, the dispersed phase is dispersed into fine droplets. After the addition is complete, stirring and temperature are maintained for emulsification and maturation for approximately 20–40 minutes to form a stable emulsion. At this point, the peptide material assembles into nanoparticles. These nanoparticles are amphiphilic, hydrophobic internally and hydrophilic externally, and can coat the surface of the nitrocellulose droplets to form a protective film. When droplets collide, this protective film prevents them from adhering to each other, maintaining their spherical shape and preventing them from agglomerating into irregularly shaped large aggregates.

[0109] Under continuous stirring, the system temperature was raised to 78-84°C at a slow rate of 0.5-1.0 °C / min. Ethyl acetate solution has a certain solubility in water. This process lasted approximately 1 hour. The heating process caused ethyl acetate to diffuse from the oil phase droplets into the aqueous phase, and some of it evaporated and was condensed and refluxed for recovery. This process induced homogeneous nucleation of nitrocellulose molecules within the droplets. At this time, the nanoparticles maintained their morphology, and the ethyl acetate solvent inside the droplets diffused outwards through the gaps between the nanoparticles or evaporated to complete dissolution. The droplets gradually hardened and solidified to form spherical propellants.

[0110] The temperature is further increased to 84~98℃, and stirring is maintained at the target temperature for 1-3 hours to ensure that the solvent is fully diffused and the particle morphology is stable. At this time, the polypeptide nanoparticles disassemble and assemble into water-soluble polypeptide molecules, which diffuse from the surface of the spherical propellant particles into the continuous phase.

[0111] After the dissolution preparation process is completed, the mixture is naturally cooled to room temperature, and the solid particles are separated from the mother liquor by filtration or centrifugation to obtain the spherical propellant in this embodiment.

[0112] The morphology of the obtained spherical propellant was observed using an optical microscope (Rayon optical microscope, magnification 4×-100×), such as Figure 4 As shown in the figure, the spherical propellant obtained after dissolution exhibits a uniform size distribution and good sphericity. Extensive statistical analysis of its size and sphericity yielded sphericity data, as shown in the figure. Figure 5 As shown, sphericity is as follows Figure 6 As shown in the figure, the spherical propellant obtained after dissolution is about 150 μm in size and has a sphericity of about 0.8, which proves that the obtained spherical propellant has good size uniformity and sphericity.

[0113] In addition, this embodiment also removes the polypeptide material of the above-mentioned spherical propellant by washing, as detailed below.

[0114] After separating the solid particles from the mother liquor by filtration or centrifugation, add 50 ml of deionized water and the prepared spherical propellant to a 200 ml beaker. Stir at a constant and moderate stirring speed (300-600 rpm) for 3-5 minutes. Separate the solid particles from the mother liquor by filtration or centrifugation to complete the first washing. Add 50 ml of deionized water and the prepared spherical propellant to a 200 ml beaker again. Stir at a constant and moderate stirring speed (300-600 rpm) for 3-5 minutes. Separate the solid particles from the mother liquor by filtration or centrifugation and collect the washing liquid.

[0115] The detergent solution was analyzed using ultraviolet spectroscopy to observe whether there were any peptide residues. The results are as follows: Figure 7 As shown in the figure, no peptide signal peaks (190-300nm) were observed in the 200nm-500nm range, proving that the peptides on the surface of the spherical propellant prepared in Example 3 could be removed after a single wash.

[0116] The above description, in conjunction with specific embodiments, provides a further detailed explanation of the present invention. It should not be construed that the specific implementation of the present invention is limited to these descriptions. For those skilled in the art, several simple deductions or substitutions can be made without departing from the concept of the present invention, and all such deductions or substitutions should be considered to fall within the scope of protection defined by the claims submitted herein.

Claims

1. A polypeptide material for dissolving solvents, characterized in that, The structural formula is as follows:

2. The polypeptide material for dissolving according to claim 1, characterized in that, This peptide material is temperature sensitive; it can self-assemble into nanoparticles at temperatures below 84°C and disassemble into water-soluble peptide molecules at temperatures above 84°C.

3. The polypeptide material for dissolving according to claim 1, characterized in that, This polypeptide material is composed of sequentially linked assembled peptides and hydrophobic peptides, wherein... The assembled peptide sequence is shown in SEQ ID NO.5, and the hydrophobic peptide sequence is shown in SEQ ID NO.8; wherein, SEQ ID NO.5: WCFFAFAFCNFFAFAFCN; SEQ ID NO.8: FFWYYFF.

4. The polypeptide material for dissolving according to claim 3, characterized in that, The assembled peptide molecules exhibit a mixed structure of α-helical and β-sheet secondary structures. In solutions with temperatures below 84°C, the dissolution-removing peptide material molecules are assembled into nanoparticles by relying on the hydrogen bond network formed by the β-sheet and α-helical secondary structures between the assembled peptides and the π-π stacking hydrophobic interactions between the hydrophobic peptides.

5. The polypeptide material for dissolving according to claim 4, characterized in that, The spatial structure of the nanoparticle is any one of α-helix, β-sheet, π-π stacking, or a combination of at least two of these.

6. The polypeptide material for dissolving according to claim 1, characterized in that, The peptide sequence of the dissolving polypeptide material is shown in SEQ ID NO.5, and the hydrophobic peptide sequence is shown in SEQ ID NO.

8.

7. A method for preparing a dissolution-removing polypeptide material as described in claim 6, characterized in that, Includes the following steps; Step 1: Remove the Fmoc protecting group at the N-terminus of phenylalanine Wang resin with a modification density of 0.35 mM by using a mixed solution of hexahydropyridine and N,N-dimethylformamide in a volume ratio of 1:4 to obtain phenylalanine Wang resin. Step 2: Add coupling agent to phenylalanine and benzotriazole-N,N,N',N'-tetramethylurea hexafluorophosphate and stir to dissolve; transfer the solution to a peptide synthesis tube and react for 45 min; at this time, phenylalanine has been coupled to the phenylalanine Wang resin in Step 1 to obtain phenylalanine-phenylalanine; Step 3: Repeat Step 2, replacing phenylalanine in Step 2 with tyrosine, tryptophan, phenylalanine, phenylalanine, asparagine, cysteine, phenylalanine, alanine, phenylalanine, alanine, phenylalanine, phenylalanine, asparagine, cysteine, phenylalanine, alanine, phenylalanine, phenylalanine, phenylalanine, cysteine ​​and tryptophan in sequence, and forming peptide resin through condensation reaction; Step 4: Wash the peptide resin into the peptide synthesis tube with N,N-dimethylformamide. Remove the synthesized peptide from the resin with a trifluoroacetic acid solution containing 2.5% water and 2.5% triisopropylsilane, while removing the side chain protection of the amino acids. After removing the trifluoroacetic acid, precipitate the crude peptide product with anhydrous diethyl ether, wash and dry to obtain the peptide material for dissolution.

8. The method for preparing the dissolution-removing polypeptide material according to claim 7, characterized in that, The coupling agent is a mixed solution of N-methylmorpholine and N,N-dimethylformamide in a volume ratio of 5:

95.

9. The application of a dissolving polypeptide material in the preparation of spherical propellants, characterized in that, Includes the following steps; Step 1: Prepare the dispersed phase and the continuous phase separately; Ethyl acetate was chosen as the solvent for the dispersed phase, and nitrocellulose was added to prepare a nitrocellulose solution. The continuous phase is made of water as a solvent, and a dissolution-removing polypeptide material as described in any one of claims 1-6 is added; Step 2: Add the dispersed phase to the continuous phase under continuous stirring and stir. The dispersed phase is dispersed into fine droplets and then dissolved to obtain the spherical propellant.

10. The application of the dissolution-removing polypeptide material according to claim 9 in the preparation of spherical propellants, characterized in that, The dissolution process is as follows: When the temperature is 64~78℃, the polypeptide material assembles into nanoparticles on the surface of the droplets by hydrogen bonds, van der Waals forces and π-π interactions. The nanoparticles are amphiphilic, hydrophobic inside and hydrophilic outside, and form a protective film on the surface of the nitrocellulose droplets. When the droplets collide with each other, the protective film prevents the droplets from sticking together and keeps the droplets spherical. When the temperature rises to 78~84℃, the ethyl acetate solvent inside the droplet diffuses outward through the gaps between the nanoparticles or evaporates to complete the dissolution, and the droplet gradually hardens and solidifies to form a spherical propellant. When the temperature continues to rise to 84~98℃, the polypeptide nanoparticles disassemble into water-soluble polypeptide molecules, which are then removed from the surface of the spherical propellant by washing. The dissolution process is then complete, and the spherical propellant is obtained.

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