CN112390872B - Keratin peptide derivative and preparation method, application and pharmaceutical composition thereof - Google Patents

Keratin peptide derivative and preparation method, application and pharmaceutical composition thereof Download PDF

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CN112390872B
CN112390872B CN202011259774.8A CN202011259774A CN112390872B CN 112390872 B CN112390872 B CN 112390872B CN 202011259774 A CN202011259774 A CN 202011259774A CN 112390872 B CN112390872 B CN 112390872B
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牛江秀
袁铭
王立业
张岩松
范艳利
刘向慧
张静晓
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Abstract

The invention belongs to the technical field of biomedical materials, and particularly relates to a keratin peptide derivative, and a preparation method, application and a pharmaceutical composition thereof. The structure of the keratin peptide derivative is shown as a formula I, and R is a hydrophobic group. The keratin peptide derivative of the invention introduces hydrophobic groups on the keratin peptide structure, can form nano particles through self-assembly in an aqueous medium, not only has the sustained and controlled release function, but also has biological adhesiveness, and is a drug carrier with good performance.
Figure DDA0002774266040000011

Description

Keratin peptide derivative and preparation method, application and pharmaceutical composition thereof
Technical Field
The invention belongs to the technical field of biomedical materials, and particularly relates to a keratin peptide derivative, and a preparation method, application and a pharmaceutical composition thereof.
Background
Keratin is structural protein of ectoderm cell, widely exists in organism tissues of fur, horn, hoof, shell, claw, scale and the like of human and animals, has rich sources in nature, and can reach dozens of thousands of tons of annual output in China. Keratin can be divided into soft keratin and hard keratin according to whether fibrosis exists, the contents of sulfur-containing amino acid in the structures of the soft keratin and the hard keratin are different, and the soft keratin mainly exists in skin tissues and cell tissues. The hard keratin is fibrous protein, mainly exists in animal epidermis and eggshell inner membrane, and has protective effect on organism. Keratin molecules are divided into two classes of alpha-keratin and beta-keratin according to the difference of secondary structures, and the keratin structure is rich in cystine and hydroxy amino acid and can be adhered to cells or mucous membranes through the actions of disulfide bonds, hydrogen bonds, ionic bonds and the like.
The natural keratin is a natural polymer material which can be directly used or used after physical and chemical modification, has various excellent performances such as renewability, biocompatibility, biodegradability, thermal stability and the like, and has good application value and development prospect, so that further research and development are needed. Keratin peptide is a hydrolysate of keratin, and in recent years, with the deep development of theories and application researches on keratin peptide materials, the water-soluble small molecular peptide has started to be widely applied to industries such as medicine, cosmetics, food, textile and the like due to the effects and effects of good affinity, moisture retention, oxidation resistance, hair repair, mitosis promotion of mammalian cells, higher nutrition and the like.
The keratin peptide structure is rich in cysteine, serine and hydroxy amino acid, and contains cell adhesion peptide sequence, such as common adhesion peptide RGD and LDV, which can be recognized by integrin on cell membrane and participate in adhesion between cell and matrix. Although keratin peptide has many advantages as a natural adhesive biomaterial, the keratin peptide has the defects of poor reproducibility, limited physical and chemical properties and the like. Therefore, appropriate modifications are required to enhance the applicability thereof.
In view of this, the invention is particularly proposed.
Disclosure of Invention
The first purpose of the invention is to provide a keratin peptide derivative.
The second object of the present invention is to propose a process for the preparation of the keratin peptide derivatives.
The third object of the present invention is to propose the use of the keratin peptide derivative.
The fourth object of the present invention is to propose a pharmaceutical composition containing the keratin peptide derivative.
In order to achieve the purpose of the invention, the technical scheme is as follows:
the invention provides a keratin peptide derivative, which has a structure shown in a formula I:
Figure BDA0002774266020000021
wherein, the Keratin Pepide represents Keratin peptide, R is hydrophobic group, preferably at least one of alkyl with 8-18 carbon atoms and cyclopentane multi-hydrogen phenanthryl.
Optionally, the cyclopentane multi-hydrogen phenanthryl group is selected from the substituents shown in formula II:
Figure BDA0002774266020000022
wherein R is1、R2Each independently selected from alkyl with 1-6 carbon atoms, R3Selected from alkylene with 1-12 carbon atoms, R' is independently selected from hydroxyl and alkyl with 1-6 carbon atoms; n is 1-10;
preferably, the cyclopentane multi-hydrogen phenanthryl group is selected from the group consisting of the substituents represented by formula IIA:
Figure BDA0002774266020000031
optionally, the keratin peptide has a molecular weight of 300-8000 Da.
The invention also relates to a process for the preparation of the above keratin peptide derivatives, comprising at least the following steps:
s1, dissolving R-COOH in a reaction solvent, and adding EDC and NHS to activate carboxyl;
s2, adding keratin peptide, and carrying out condensation reaction with the activated carboxyl;
s3, extracting the condensation product to obtain the keratin peptide derivative.
Preferably, R-COOH is a hydrophobic compound, preferably deoxycholic acid or C8-18 alkyl acid.
Optionally, the weight ratio of R-COOH to reaction solvent is 1: 10-80 parts; the reaction solvent is preferably at least one of methanol, ethanol, chloroform and N, N-dimethylformamide; preferably, the reaction temperature of the activated carboxyl is 15-25 ℃, the reaction time is 8-36 hours, and the reaction condition is a light-shielding reaction; still more preferably, the weight ratio of R-COOH, EDC and NHS is 1: 10-500: 20 to 600.
Optionally, in S2, the keratin peptide is dissolved in a buffer solution, wherein the buffer solution is one of a citric acid-sodium hydroxide-hydrochloric acid buffer solution, a phosphate buffer solution, and a potassium dihydrogen phosphate-sodium hydroxide buffer solution;
preferably, the condensation reaction is carried out at the reaction temperature of 15-25 ℃ for 4-24 hours under the reaction condition of light shielding.
Optionally, the extraction condensation product comprises: placing the product after the condensation reaction in a dialysis bag with the molecular weight cutoff of 300-14000 Da, dialyzing in deionized water at 0-10 ℃ for 3-8 days, and drying to obtain the keratin peptide derivative; the drying is preferably one of freeze drying, spray drying or drying under reduced pressure.
Optionally, the coupling rate of the R-COOH and the keratin peptide is 18-90%.
The invention also relates to the use of the keratin peptide derivatives as drug carriers; preferably, the pharmaceutical carrier comprises a pharmaceutical carrier for gastrointestinal administration, ocular administration, dermal administration, nasal mucosal administration, rectal administration or vaginal administration.
The invention also relates to a drug carrier prepared by adopting the keratin peptide derivative, and the preparation method of the drug carrier comprises the following steps: dissolving the keratin peptide derivative and the drug in a pharmaceutically acceptable solvent, evaporating to form a layer of film, drying the film, and adding a hydration medium to demould to obtain the drug carrier; preferably, the evaporation is rotary evaporation, the time is 10-40 min, the temperature is 15-25 ℃, and the reaction condition is a light-shielding reaction; more preferably, the hydration medium is buffer solution, deionized water or distilled water; further preferably, the particle size of the drug carrier is 5-1000 nm.
The invention also relates to a pharmaceutical composition, which comprises a medicament and a medicament carrier, wherein the medicament carrier is the keratin peptide derivative or the medicament carrier; preferably, the drug comprises at least one of a chemotherapeutic drug, an antipyretic analgesic, a steroidal anti-inflammatory drug, a non-steroidal anti-inflammatory drug, a digestive system drug, a circulatory system drug, a nervous system drug, a hypoglycemic agent, a diuretic agent, and a hormonal drug, and the chemotherapeutic drug comprises an antibiotic and an antineoplastic agent; the dosage form of the pharmaceutical composition is selected from a liquid dosage form, a semisolid dosage form, a solid dosage form or a spray dosage form, the liquid dosage form is a colloidal fluid, an emulsion or a suspension, and the semisolid dosage form is an ointment, a gel or a suppository.
The technical scheme of the invention at least has the following technical effects:
the keratin peptide derivative can form nano particles through self assembly in an aqueous medium, is used as a delivery carrier of medicaments or active substances, is rich in cysteine, serine and hydroxyl amino acid, contains a cell adhesion peptide sequence, such as common adhesion peptide RGD and LDV, can be recognized by integrin on a cell membrane and participates in adhesion between cells and a matrix, prolongs the retention time of the carrier on the surfaces of the cells and mucous membranes, and promotes the absorption of medicaments; can also improve the local drug concentration and enhance the local targeting of the drug.
The keratin peptide derivative can be self-assembled in an aqueous medium to form a nano carrier, and has better entrapment on pharmaceutically active molecules.
The keratin peptide derivative is used as a drug carrier for gastrointestinal tract administration, eye administration, skin administration, nasal mucosa administration, rectal administration or vaginal administration and other ways of administration, has a slow release effect, and can reduce the administration times.
Drawings
FIG. 1 is a 1HNMR spectrum of deoxycholic acid-keratin peptide derivative;
FIG. 2 is a fluorescence spectrum of the critical micelle concentration of deoxycholic acid-keratin peptide derivatives;
FIG. 3 is a scanning electron microscope image of a podophyllotoxin-loaded keratin peptide derivative nano-carrier;
FIG. 4 is a distribution diagram of particle size of the podophyllotoxin keratin peptide derivative-loaded nano-carrier.
Detailed Description
It should be noted that the following detailed description is exemplary and is intended to provide further explanation of the disclosure. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.
It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of exemplary embodiments according to the present application. As used herein, the singular forms also include the plural forms unless the context clearly dictates otherwise, and further, it is understood that when the terms "comprises" and/or "comprising" are used in this specification, they specify the presence of the stated features, steps, operations, devices, components, and/or combinations thereof.
The technical solutions of the present invention will be described clearly and completely with reference to the following embodiments, and it should be understood that the described embodiments are some, but not all, embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The embodiment of the invention provides a keratin peptide derivative, which has a structure shown in a formula I:
Figure BDA0002774266020000051
Figure BDA0002774266020000061
wherein, the Keratin Pepide represents Keratin peptide, R is hydrophobic group, preferably at least one of alkyl with 8-18 carbon atoms and cyclopentane multi-hydrogen phenanthryl.
In the embodiment of the invention, after the keratin peptide is subjected to hydrophobic modification, the keratin peptide can form nano particles through self-assembly, and the nano particles are used as a delivery carrier of a medicament or an active substance, have a sustained and controlled release effect and biological adhesiveness, can promote the absorption of the medicament or the active substance, and improve the bioavailability of the medicament or the active substance.
Optionally, the cyclopentane multi-hydrogen phenanthryl group is selected from the group consisting of substituents represented by formula II:
Figure BDA0002774266020000062
wherein R is1、R2Each independently selected from alkyl groups having 1 to 6 carbon atoms, preferably methyl, ethyl, n-propyl and isopropyl, preferably methyl.
Figure BDA0002774266020000063
Indicates the substitution position.
R3Selected from alkylene with 1-12 carbon atoms;
r' is n, and is independently selected from hydroxyl and alkyl with 1-6 carbon atoms; n is 1 to 10.
Optionally, the cyclopentane polyhydrophenanthryl group is selected from substituents represented by formula IIA:
Figure BDA0002774266020000064
wherein the content of the first and second substances,
Figure BDA0002774266020000065
indicates the substitution position.
In the embodiment of the invention, the molecular weight of the keratin peptide is 300-8000 Da.
The embodiment of the invention also relates to a preparation method of the keratin peptide derivative, which at least comprises the following steps:
s1, dissolving R-COOH in a reaction solvent, and adding EDC and NHS to activate carboxyl;
s2, adding keratin peptide, and carrying out condensation reaction with the activated carboxyl;
s3, extracting the condensation product to obtain the keratin peptide derivative.
Specifically, R-COOH is a hydrophobic compound, and is specifically selected from deoxycholic acid or alkyl acid with 8-18 carbon atoms.
In S1, the weight ratio of R-COOH to the reaction solvent is 1: 10-80, wherein the reaction solvent is at least one selected from methanol, ethanol, chloroform and N, N-dimethylformamide, and preferably methanol.
In S1, the reaction temperature of the activated carboxyl is 15-25 ℃, the reaction time is 8-36 hours, and the reaction condition is a light-shielding reaction. And stirring is preferred to accelerate the reaction.
In S1, the weight ratio of R-COOH, EDC (1-ethyl-3- (3-dimethylaminopropyl) -carbodiimide) and NHS (N-hydroxysuccinimide) is 1: 10-500: 20 to 600.
In S2, dissolving the keratin peptide in a buffer solution, wherein the buffer solution is one of a citric acid-sodium hydroxide-hydrochloric acid buffer solution, a phosphate buffer solution, and a potassium dihydrogen phosphate-sodium hydroxide buffer solution;
in S2, the condensation reaction is carried out at the temperature of 15-25 ℃ for 4-24 hours under the condition of light shielding. And stirring is preferred to accelerate the reaction.
In S3, the step of extracting the condensation product comprises: and (3) putting the product after the condensation reaction into a dialysis bag with the molecular weight cutoff of 300-14000 Da, dialyzing for 3-8 days in deionized water at 0-10 ℃, and drying to obtain the keratin peptide derivative disclosed by the embodiment of the invention.
Wherein the drying is selected from one of freeze drying, spray drying or drying under reduced pressure.
According to H-NMR spectrum analysis, the coupling rate of the hydrophobic compound and the keratin peptide in the preparation method of the embodiment of the invention is 18-90%.
The preparation of the examples of the invention is further illustrated below by the reaction of the keratin peptide with deoxycholic acid:
weighing deoxycholic acid powder in a dry anhydrous round-bottom flask, adding a reaction solvent into the flask, uniformly stirring to completely dissolve the deoxycholic acid powder, then adding EDC and NHS, uniformly stirring for 4-24 hours at room temperature in a dark place, slowly adding keratin peptide phosphoric acid to slowly dissolve the mixture, reacting for 2-24 hours at room temperature in a dark place, placing the mixture in a dialysis bag with the molecular weight cutoff of 300-14000 Da, dialyzing for 3-8 days at 0-10 ℃ in deionized water, and drying to obtain solid powder, namely the keratin peptide derivative. The deoxycholic acid-keratin peptide derivative has an entrapment rate of 92.20% (w/w) on podophyllotoxin, an entrapment rate of 85.0% on ibuprofen and a loading rate of 89.50% on indomethacin.
The preparation of the present examples is further illustrated by the reaction of keratin peptides with alkyl acids:
weighing alkyl acid in a dry anhydrous round-bottom flask, adding a reaction solvent into the flask, uniformly stirring to completely dissolve the alkyl acid, then adding EDC and NHS, uniformly stirring for 4-24 hours at room temperature in a dark place, slowly adding keratin peptide phosphoric acid for buffer dissolution, reacting for 2-24 hours at room temperature in a dark place, placing the mixture in a dialysis bag with the molecular weight cutoff of 300-14000 Da, dialyzing for 3-8 days at 0-10 ℃ in deionized water, and drying to obtain solid powder, namely the alkyl acid-keratin peptide derivative.
The embodiment of the invention also relates to the application of the keratin peptide derivative as a drug carrier. Preferably, the pharmaceutical carrier comprises a drug-loaded carrier for gastrointestinal administration, ocular administration, dermal administration, nasal mucosal administration, rectal administration or vaginal administration. The keratin peptide derivative can be self-assembled in an aqueous medium to form a nano carrier, has good entrapment on pharmaceutically active molecules, has a slow release effect, and can reduce the administration times.
The embodiment of the invention also relates to a drug carrier prepared from the keratin peptide derivative, and the preparation method of the drug carrier comprises the following steps: dissolving the keratin peptide derivative and the drug in a pharmaceutically acceptable solvent, evaporating to form a film, drying the film, adding a hydration medium, and demolding to obtain the drug carrier.
Preferably, evaporation and rotary evaporation are carried out for 10-40 min at the temperature of 15-25 ℃, and the reaction condition is a light-shielding reaction;
more preferably, the hydration medium is buffer solution, deionized water or distilled water; specifically, the buffer solution may be a phosphate buffer solution.
Further preferably, the particle size of the drug carrier is 5-1000 nm.
The embodiment of the invention also relates to a pharmaceutical composition, which comprises a medicament and a medicament carrier, wherein the medicament carrier comprises the keratin peptide derivative or is the medicament carrier.
Specifically, the drug comprises at least one of chemotherapeutic drugs, antipyretic analgesics, steroidal anti-inflammatory drugs, non-steroidal anti-inflammatory drugs, digestive system drugs, circulatory system drugs, nervous system drugs, hypoglycemic agents, diuretic agents and hormonal drugs; chemotherapeutic drugs include antibiotics and antineoplastic drugs; the specific drug can be selected from: ibuprofen, indomethacin, podophyllotoxin, methotrexate, tretinoin, cyclosporin a, doxorubicin, paclitaxel, atorvastatin, nifedipine, enalapril maleate, furosemide, spironolactone, isosorbide mononitrate, gliclazide, cefuroxime, nizatidine, nimodipine, meloxicam, bicyclol, estazolam, berberine hydrochloride and the like, but is not limited to these drugs.
The dosage form of the pharmaceutical composition of the embodiment of the invention is selected from liquid dosage forms, semisolid dosage forms, solid dosage forms or spray dosage forms, the liquid dosage forms are colloid liquid, emulsion or suspension, and the semisolid dosage forms are ointments, gels or suppositories.
The present invention will be described in further detail with reference to examples and drawings, but the present invention is not limited thereto.
Example 1: preparation of deoxycholic acid-keratin peptide derivatives
1. Weighing 0.2g of deoxycholic acid powder into a dry anhydrous round-bottom flask, adding 15mL of methanol into the flask, stirring at a constant speed for 30min to completely dissolve the deoxycholic acid powder, then adding 96mg of EDC and 70mg of NHS, stirring at a constant speed overnight at room temperature in a dark condition, and rotating at a speed of 60r/min to obtain a deoxycholic acid solution with activated carboxyl terminals.
2. Keratin peptide powder (1.0 g) was weighed into a round-bottomed flask, and 30mL of a phosphate buffer solution having a pH of 6 was added to the flask and stirred to dissolve sufficiently.
3. The solution of the keratin peptide is slowly dripped into the deoxycholic acid solution activated at the carboxyl terminal, and the mixture is stirred for 12 hours at room temperature in a dark place. The obtained solution is placed in a dialysis bag with the molecular weight cutoff of 300Da and is dialyzed for 72 hours by deionized water. Drying the dialyzed solution by a freeze dryer to obtain deoxycholic acid-keratin peptide derivative powder. The chemical reaction equation for this step is shown below.
Figure BDA0002774266020000091
Dissolving deoxycholic acid-keratin peptide derivative in deuterated water to obtain a sample with a concentration of 10mg/mL, and subjecting the sample to a 400MHz NMR spectrometer (Bruker, Germany, model: AVANCE III 400M)1HNMR characterization, the results are shown in FIG. 1.
As can be seen from the nuclear magnetic resonance spectrum in figure 1, after the keratin peptide is modified by deoxycholic acid, a characteristic peak of deoxycholic acid appears at delta 0.6-2.5 ppm, and a characteristic peak of keratin is remained at delta 0.7-2.4 ppm, so that the success of deoxycholic acid-keratin peptide synthesis is proved.
Example 2: determination of the critical micelle concentration of deoxycholic acid-keratin peptide derivatives:
25mg of the deoxycholic acid-keratin peptide derivative prepared in example 1 was precisely weighed, and a volume of 25mL was determined using a PBS solution with a pH of 7.4, to obtain a 1.0mg/mL deoxycholic acid-keratin peptide derivative solution. Then diluted with PBS to various concentrations ranging from 5.0X 10-4mg/mL to 0.5 mg/mL. 0.1mL of 2X 10 cells were removed-4Acetone solution of pyrene in mol/L was placed in a glass test tube and nitrogen gas was blown off the acetone. 10mL of different concentrations of Ketocholic acid-KetochoreAdding the protein peptide solution into a 10mL test tube containing pyrene, performing water bath ultrasound for 30min at room temperature, wherein the excitation wavelength is 334nm, scanning the excitation spectrum and the emission spectrum of pyrene within the emission wavelength range of 350-500 nm, and passing the ratio of the fluorescence intensity of 373nm to 384nm (I)1/I3) To determine the critical micelle concentration of the deoxycholic acid-keratin peptide derivative. The critical micelle concentration determination fluorescence spectrum of the deoxycholic acid-keratin peptide derivative is shown in fig. 2.
As can be seen from FIG. 2, as the concentration of deoxycholic acid-keratin peptide derivatives increased, the fluorescence intensity of pyrene decreased, I1/I3It abruptly decreases at 0.05mg/mL, and therefore the critical micelle concentration of the deoxycholic acid-keratin peptide derivative is 0.05 mg/mL.
Example 3: preparing a deoxycholic acid-keratin peptide derivative-carried podophyllotoxin carrier:
adopting a film dispersion method to prepare the deoxycholic acid-keratin peptide derivative podophyllotoxin-loaded carrier: dispersing podophyllotoxin and deoxycholic acid-keratin peptide derivative in ethanol, and performing rotary evaporation for 30min to form a layer of film; vacuum drying for 2 h; spin hydrating at 25 deg.C until completely demoulding; treating the carrier with water bath ultrasonic at 5 deg.C for 5min, and filtering with 0.22 μm microporous membrane to obtain deoxycholic acid-keratin peptide derivative-carried podophyllotoxin carrier.
Appearance morphology observation of the deoxycholic acid-keratin peptide derivative-carried podophyllotoxin carrier:
placing a sample of deoxycholic acid-keratin peptide derivative-carried podophyllotoxin carrier on a copper sheet, fixing the copper sheet with the sample on a sample table by using a conductive double faced adhesive tape, spraying platinum, setting the accelerating voltage to be 5kV, and observing the appearance and the shape of the copper sheet by using a scanning electron microscope (model: Zeiss Sigma 500). The scanning electron micrograph of the podophyllotoxin keratin peptide derivative-loaded nano-carrier is shown in figure 3.
As can be seen from FIG. 3, the drug-loaded carrier is mostly irregular cylindrical and spherical in appearance, good in dispersion and free of agglomeration.
Determination of the particle size distribution of the deoxycholic acid-keratin peptide derivative-supported podophyllotoxin carrier:
the deoxycholic acid-keratin peptide derivative podophyllotoxin-loaded carrier is diluted by 50 times, the particle size distribution and the polydispersity index (PDI) of the drug-loaded carrier are measured by a laser particle sizer (English Malvern, model: Nano ZS90), the light source is a He-Ne laser source, the measurement angle is 90 degrees, the laser wavelength is 633nm, and the measurement temperature is 25 ℃. The particle size distribution of the deoxycholic acid-keratin peptide derivative podophyllotoxin-loaded carrier is shown in figure 4.
As can be seen from FIG. 4, the mean particle size of the deoxycholic acid-keratin peptide derivative podophyllotoxin-loaded carrier is (181.5 + -63.65) nm, and the PDI is 0.12, which indicates that the structure is stable, the particle size is in monomodal distribution, and the distribution is narrow.

Claims (7)

1. A keratin peptide derivative, wherein the structure of the keratin peptide derivative is shown as formula I:
Figure 704244DEST_PATH_IMAGE001
（I）；
wherein, the Keratin Pepide represents Keratin peptide, and the molecular weight of the Keratin peptide is 300-8000 Da; r is a substituent shown in formula IIA:
Figure 833874DEST_PATH_IMAGE002
（IIA）。
2. a process for the preparation of a keratin peptide derivative as claimed in claim 1, comprising at least the following steps:
s1, dissolving R-COOH in a reaction solvent, and adding EDC and NHS to activate carboxyl;
s2, adding keratin peptide, and carrying out condensation reaction with the activated carboxyl;
s3, extracting a condensation product to obtain the keratin peptide derivative;
R-COOH is deoxycholic acid;
the weight ratio of R-COOH, EDC and NHS is 1: 10-500: 20 to 600.
3. The method according to claim 2, wherein the weight ratio of R-COOH to the reaction solvent is 1: 10-80 parts;
at least one of methanol, ethanol, chloroform and N, N-dimethylformamide is used as the reaction solvent;
the reaction temperature of the activated carboxyl is 15-25 ℃, the reaction time is 8-36 hours, and the reaction condition is a light-shielding reaction.
4. The method according to claim 2, wherein in S2, the keratin peptide is dissolved in a buffer solution, the buffer solution being one of a citric acid-sodium hydroxide-hydrochloric acid buffer solution, a phosphate buffer solution, a potassium dihydrogen phosphate-sodium hydroxide buffer solution;
the condensation reaction is carried out at the reaction temperature of 15-25 ℃ for 4-24 hours under the reaction condition of light shielding.
5. The method of claim 2, wherein extracting the condensation product comprises:
putting the product after the condensation reaction into a dialysis bag with the molecular weight cutoff of 300-14000 Da, dialyzing in deionized water at 0-10 ℃ for 3-8 days, and drying to obtain the keratin peptide derivative;
the drying is one of freeze drying, spray drying or reduced pressure drying.
6. Use of the keratin peptide derivative of claim 1 as a pharmaceutical carrier for the preparation of a pharmaceutical composition;
the drug carrier comprises drug carriers for gastrointestinal administration, ocular administration, skin administration, nasal mucosa administration, rectal administration or vaginal administration.
7. A pharmaceutical composition comprising a drug and a drug carrier, said drug carrier comprising the keratin peptide derivative of claim 1;
the drug comprises at least one of chemotherapeutic drugs, antipyretic analgesics, steroidal anti-inflammatory drugs, non-steroidal anti-inflammatory drugs, digestive system drugs, circulatory system drugs, nervous system drugs, hypoglycemic drugs, diuretic drugs and hormonal drugs, and the chemotherapeutic drugs comprise antibiotics and antineoplastic drugs;
the dosage form of the pharmaceutical composition is selected from a liquid dosage form, a semisolid dosage form, a solid dosage form or a spray dosage form, the liquid dosage form is a colloidal fluid, an emulsion or a suspension, and the semisolid dosage form is an ointment, a gel or a suppository.
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