Sialic acid group-containing polyglycerol fatty acid ester derivative as well as synthesis method and application thereof in preparation of pharmaceutical preparation

Abstract

The invention belongs to the technical field of medicines, and particularly relates to a polyglycerol fatty acid ester derivative SAm-PGn-HC containing sialic acid groups, a synthesis method of the polyglycerol fatty acid ester derivative SAm-PGn-HC and application of the polyglycerol fatty acid ester derivative SAm-PGn-HC in pharmaceutical preparations, in particular to preparation and modification of particle preparations. According to the polyglycerol fatty acid ester derivative containing the sialic acid group, carboxyl on a sialic acid molecule is connected with hydroxyl on polyglycerol fatty acid ester through an ester bond, the structural formula is shown in the formula (I), SA represents the sialic acid group, PG represents a polyglycerol fatty acid ester fragment, HC represents a hydrocarbon chain, m represents the number of SA fragments grafted in a PG molecule, and m represents the number of the SA fragments grafted in the PG molecule. N represents the polymerization degree of polyglycerol in the PG fragment, x represents the number of carbon atoms of a hydrocarbon chain, m is greater than or equal to 1 and less than or equal to 100, and n is greater than or equal to 1 and less than or equal to 100. # imgabs0 #

Description

Technical Field

[0001] The invention belongs to the field of medical technology, and specifically relates to a polyglycerol fatty acid ester derivative containing a sialic acid group, a synthesis method thereof and an application thereof in the preparation of a pharmaceutical preparation, in particular to the preparation and modification of a microparticle preparation. Background Art

[0002] Inflammatory diseases refer to a series of diseases caused by inflammatory reactions, which are an immune response of the body to infection, injury or chronic stimulation. Its pathological manifestations include vasoconstriction or dilation, congestion, congestion, accumulation of immune cells, fluid exudation and fibrin deposition, etc. Continuous acute inflammation will promote the development of chronic inflammation, causing adverse effects such as tissue damage, fibrosis and necrosis.

[0003] Neutrophils are the most abundant and fastest-responding innate immune effector cells in the blood, and are usually the first wave of immune cells to infiltrate the inflammatory site on a large scale. Under the activation of the inflammatory cascade, neutrophils can proliferate rapidly, prolong their lifespan, and aggravate tissue damage by releasing inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), matrix metalloproteinases (MMPs), neutrophil elastase (NE), and reactive oxygen species (ROS). Existing strategies for treating inflammatory diseases with neutrophils usually include inhibiting the proliferation and development of neutrophils, eliminating neutrophils, inhibiting the migration of neutrophils to the site of inflammation, and inhibiting the specific pro-inflammatory function of neutrophils. This non-selective treatment method of inhibiting all neutrophils in the body ignores the key role of normal neutrophils in immune defense and is prone to secondary infection of the body. Therefore, it is necessary to develop a method that can enable the preparation to specifically target and activate neutrophils.

[0004] During the inflammatory response, activated neutrophils will highly express an adhesion molecule that can specifically bind to sialic acid (SA), namely L-selectin (CD62L). Therefore, modifying the surface of the preparation with sialic acid is expected to target inflammatory neutrophils to inhibit their uncontrolled infiltration and over-activation, providing a feasible method for neutrophil-targeted treatment.

[0005] Polyglycerol fatty acid ester (PG) is a surfactant with excellent performance, which has good emulsification, dispersion, wetting, stability and other surface properties, and has been widely used in medicine, food, cosmetics and other fields. At the same time, the use of PG in preparations can avoid the adverse reactions induced by repeated administration of PEG-modified preparations due to its low immunogenicity and other characteristics.

[0006] Therefore, by providing a polyglycerol fatty acid ester derivative containing a sialic acid group and enabling it to be stably modified on the surface of a microparticle preparation, a series of pharmaceutical preparations with high biosafety and the ability to specifically target and activate neutrophils can be prepared, which is expected to provide a solution to the technical problems that urgently need to be solved in this field. Summary of the invention

[0007] The purpose of the present invention is to provide a polyglycerol fatty acid ester derivative (SAm-PGn-HC) containing a sialic acid group, a synthesis method thereof, and an application thereof in the preparation of a pharmaceutical preparation. By modifying the pharmaceutical preparation with SAm-PGn-HC, it is possible to solve the disadvantage of the preparation in non-specifically killing all neutrophils in the body while retaining the structural integrity and functionality of the preparation, improve the selectivity of the preparation, and enable it to be accurately released at the site of inflammation.

[0008] To achieve the above object, the technical solution of the present invention is as follows:

[0009] Provided is a polyglycerol fatty acid ester derivative (SAm-PGn-HC) containing a sialic acid group, wherein the carboxyl group on the sialic acid molecule is connected to the hydroxyl group on the polyglycerol fatty acid ester through an ester bond, and the structural formula is:

[0010]

[0011] Wherein SA represents a sialic acid group, PG represents a polyglycerol monofatty acid ester fragment, HC represents a hydrocarbon chain, m represents the number of SA fragments grafted into the PG molecule, n represents the degree of polymerization of polyglycerol in the PG fragment, and x represents the number of carbon atoms in the hydrocarbon chain, 1≤m≤100, 1≤n≤100.

[0012] Preferably, the above-mentioned polyglycerol fatty acid ester derivative containing sialic acid groups has 1≤m≤13 and 1≤n≤12.

[0013] In some embodiments, the polyglycerol portion of PGn has 1-100 glycerol repeating units and an average molecular weight of 92-7400 Daltons; preferably, the polyglycerol portion of PG has 1-40 glycerol repeating units and an average molecular weight of 92-3000 Daltons; more preferably, the polyglycerol portion of PG has 1-12 glycerol repeating units and an average molecular weight of 92-1500 Daltons.

[0014] In some embodiments, the number of non-polar hydrocarbon chains of the PG is 1 to 3, namely, 1 hydrocarbon chain (polyglycerol monofatty acid ester), 2 hydrocarbon chains (polyglycerol difatty acid ester), 3 hydrocarbon chains (polyglycerol trifatty acid ester), preferably one hydrocarbon chain (polyglycerol monofatty acid ester) and two hydrocarbon chains (polyglycerol difatty acid ester).

[0015] In some embodiments, the hydrocarbon chain length of the PG comprises alkyl and alkenyl groups of 4 to 32 carbon atoms; preferably, the hydrocarbon chain of the PG is selected from one or more of caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, arachidonic acid, and oleic acid; more preferably, the hydrocarbon chain of the PG is selected from at least one of palmitic acid and stearic acid.

[0016] The present invention also provides a method for synthesizing the above-mentioned polyglycerol fatty acid ester derivative containing a sialic acid group, comprising the following steps:

[0017] 1) Under nitrogen protection, SA, PGn-HC, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) are completely dissolved in anhydrous formamide, and EDC / NHS is used as a catalyst, and stirred;

[0018] 2) adding triethanolamine (TEA) dropwise to the reaction system and continuing stirring;

[0019] 3) After the reaction is completed, the product is placed in a dialysis bag, dialyzed in a dialysis medium, 80% of the water is removed by rotary evaporation, and the remaining solution is freeze-dried to obtain SAm-PGn-HC.

[0020] Preferably, in the above-mentioned preparation method, in step 1), the molar ratio of SA (-COOH content in the structure): PGn-HC: EDC: NHS is 200:n:80:40, at which time the -COOH concentration in the SA structure in the system is 1 to 571 mg / mL, the PGn-HC concentration is 1 to 143 mg / mL, the EDC concentration is 1 to 228 mg / mL, and the NHS concentration is 1 to 114 mg / mL. The reaction conditions are stirring at 25°C for 30 min.

[0021] Preferably, in the above preparation method, after the triethanolamine (TEA) is dripped into the system in step 2), the concentration of TEA is 0.1-228 mg / mL, and the stirring time is 8 h.

[0022] Preferably, in the above preparation method, in step 3), the molecular weight cutoff of the dialysis bag is 10 kDa, the dialysis medium is distilled water, the dialysis time is to replace the dialysis medium every 4 hours, and the cumulative dialysis time is 24 hours.

[0023] The present invention also provides an application of a polyglycerol fatty acid ester derivative containing a polysialic acid group in a pharmaceutical preparation, in particular, the application of the SAm-PGn-HC in the preparation and modification of a microparticle drug delivery preparation, wherein the microparticle drug delivery preparation may be a micelle, a liposome, a vesicle, an emulsion or a nanoparticle. SAm-PGn-HC and a drug may be directly assembled into nanomicelles, or a surfactant such as phospholipids, poloxamers, tweens, spans, etc. may be selected to mix and assemble into liposomes, vesicles, emulsions or nanoparticles. The mass ratio of the drug to the SAm-PGn-HC is 1:5 to 1:100; preferably, the mass ratio of the drug to the SAm-PGn-HC is 1:10 to 1:20.

[0024] The beneficial effects of the present invention are:

[0025] 1. The polyglycerol fatty acid ester derivative SAm-PGn-HC containing sialic acid groups of the present invention connects SA and PGn-HC groups through ester bonds, has a stable structure, can be directly assembled with drugs to prepare microparticle preparations, and can be stably modified on the surface of nanoformulations; at the same time, based on the low immunogenicity of the PGn-HC fragment, the derivative exhibits high biosafety and has good prospects for application in preparations.

[0026] 2. The polyglycerol fatty acid ester derivative SAm-PGn-HC containing sialic acid groups of the present invention can actively target activated neutrophils, avoid indiscriminate killing of immune cells in the body, achieve specific immunotherapy, and have good prospects for clinical transformation. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 The synthetic route of SA11-PG10-C18 in Example 1 is shown in FIG.

[0028] Figure 2 This is the infrared spectrum of SA11-PG10-C18 in Example 1.

[0029] Figure 3 This is the hydrogen nuclear magnetic resonance spectrum of SA11-PG10-C18 in Example 1.

[0030] Figure 4 This is a graph showing the particle size determination of SA11-PG10-C18 modified liposomes and ordinary liposomes in Example 1.

[0031] Figure 5 This is a transmission electron microscopy scan of the SA11-PG10-C18 modified liposomes and ordinary liposomes in Example 1.

[0032] Figure 6This is a graph showing the levels of cytokines (where A is TNF-α and B is IL-1β) after the cells in Example 1 were co-incubated with SA11-PG10-C18 modified drug-loaded liposomes and other preparations.

[0033] Figure 7 (A) is a flow cytometric analysis of the in vitro uptake of SA11-PG10-C18 modified liposomes and other preparations by cells in Example 1, and (B) is a semi-quantitative analysis of the flow cytometric data.

[0034] Figure 8 This is a histogram of the number of neutrophils in the alveolar lavage fluid of mice after injection of SA11-PG10-C18 modified liposomes in Example 1.

[0035] Fig. 9 This is the wet weight / dry weight ratio of mouse lungs after injection of SA11-PG10-C18 modified liposomes in Example 1.

[0036] Fig.10 These are lung sections of mice after injection of SA11-PG10-C18 modified liposomes in Example 1, wherein A is a healthy control group, B is an LPS-induced model group, and C is a SA11-PG10-C18 modified liposome treatment group. DETAILED DESCRIPTION

[0037] The technical solution of the present invention is further described below by specific implementation methods. It should be understood by those skilled in the art that the embodiments are only to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0038] Example 1

[0039] (I) SA11-PG10-C18, a polyglycerol fatty acid ester derivative containing a sialic acid group, is prepared as follows:

[0040] 1) Under nitrogen protection, SA (containing 10 mmol -COOH), 0.5 mmol PG10-C18 (purchased from Shandong Binzhou Golden Eagle New Material Technology Co., Ltd.), 4 mmol 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and 2 mmol N-hydroxysuccinimide (NHS) were completely dissolved in 7 mL anhydrous formamide, with EDC and NHS as catalysts, and stirred;

[0041] 2) Add 4 mmol triethanolamine (TEA) dropwise to the reaction system and continue stirring;

[0042] 3) After the reaction is completed, the product is placed in a dialysis bag with a molecular weight cutoff of 10 kDA and dialyzed in distilled water. The dialysis medium is replaced every 4 hours for a total of 24 hours. 80% of the water is removed by rotary evaporation, and the remaining solution is freeze-dried to obtain SA11-PG10-C18.

[0043] The above synthetic route is as follows Figure 1 shown.

[0044] Characterization of polyglycerol fatty acid ester derivative SA11-PG10-C18 containing sialic acid groups:

[0045] 1) Infrared spectroscopy (IR) analysis

[0046] Take appropriate amount of SA, PG10-C18, SA11-PG10-C18 and KBr, mix them, grind them into thin slices and scan them with infrared spectrometer. The infrared spectrum is as follows: Figure 2 The spectrum of SA is at 3342 cm -1 、1726cm -1 、1654cm -1 and 1531cm -1 NH bond stretching vibration, carboxyl stretching vibration, amide I band and amide II band are shown at 2927cm -1 and 2881cm -1 The peaks at correspond to -CH 3 and -CH 2 CH 2 -Stretching vibration, 1739cm -1 The peak at 3344 cm represents the C=O stretching vibration of the ester group. -1 、2926cm -1 and 2864cm -1 NH, -CH 3 and -CH 2 CH 2 -stretching vibration peak. This indicates that an amide bond is formed between SA and PG10-C18. In addition, the carbonyl stretching vibration band of the carboxyl group in SA is replaced by the 1645 cm -1 The single carbonyl stretching vibration band related to the amide group was replaced, and the NH stretching vibration band was significantly weakened, proving that SA and PG10-C18 were successfully bonded to synthesize SA11-PG10-C18.

[0047] 2) H NMR spectroscopy ( 1 H-NMR) analysis

[0048] The structure of SA11-PG10-C18 was determined by nuclear magnetic resonance spectroscopy. Figure 3 The synthesis of the compound 1 The H-NMR spectrum showed different peaks with chemical shifts of δ0.98 (peak “a”), δ1.24 (peak “b”), δ1.89 (peak “c”), and δ2.97-4.06 (peak “d”), which corresponded to the terminal methyl groups (-CH 3 ), the middle methylene (-CH 2 CH 2 -), acetyl (-COCH 3 ) and PG10 components, which are consistent with the predicted SA11-PG10-C18 structure, further demonstrating the successful synthesis of SAPG10C18.

[0049] Preparation of SA11-PG10-C18 modified liposomes:

[0050] SA11-PG10-C18 modified liposomes were prepared by thin film dispersion technology. First, 50 mg phospholipids, 45 mg cholesterol, 5 mg SA11-PG10-C18 and 5 mg curcumin were dissolved in 5 mL ethanol and stirred at 60 ° C for 20 min to form a lipid film. Then, a warm citric acid buffer solution (containing 200 mmol of active ingredient) with a pH of 4.0 was injected into the lipid film, and stirring was continued at 60 ° C for 20 min to form a preliminary liposome. The mixture was ultrasonically treated for a total of 8 min (200 W × 2 min, 400 W × 6 min), and then filtered through a polycarbonate membrane with a pore size of 800 nm, 450 nm and 220 nm in sequence to obtain liposomes. The preparation scheme of ordinary liposomes (CL, without the addition of SA11-PG10-C18) is the same as above (phospholipids: cholesterol curcumin = 50 mg: 50 mg: 5 mg).

[0051] The particle size determination results of SA11-PG10-C18 modified liposomes and ordinary liposomes are shown in Figure 4 As shown in the transmission electron microscope scanning image Figure 5 The results show that the liposomes modified with SA11-PG10-C18 have no obvious difference from ordinary liposomes in appearance and morphology, which indicates that SA11-PG10-C18 modification has no effect on the morphology of liposomes.

[0052] Study on the anti-inflammatory effect of SA11-PG10-C18 modified liposomes in vitro:

[0053] Inflammatory sites usually recruit a large number of activated neutrophils, which then activate subsequent inflammatory cascade reactions and ultimately aggravate inflammation. This process promotes the expression of a large number of proinflammatory factors (such as TNF-α, IL-1β, etc.). The enzyme-linked immunosorbent assay was used to investigate the anti-inflammatory effect of SA11-PG10-C18 modified liposomes in vitro. Inflammatory activated neutrophils were co-incubated with PBS, free drugs, ordinary drug-loaded liposomes, and SA11-PG10-C18 modified drug-loaded liposomes (each group had an equivalent drug dose). After centrifugation of the cells, the supernatant was used to detect cytokine (TNF-α and IL-1β) levels. The results are as follows: Figure 6 As shown. Compared with PBS, ordinary drug-loaded liposomes failed to significantly inhibit the release of proinflammatory factors, which was attributed to the sustained release of drugs by liposomes. In contrast, SA11-PG10-C18 modified drug-loaded liposomes showed a therapeutic effect similar to that of free drugs by specifically targeting inflammatory activated neutrophils that express high levels of L-selectin, indicating that SA11-PG10-C18 modified liposomes can effectively inhibit the release of proinflammatory factors, thereby curbing the aggravation of inflammatory reactions.

[0054] Investigation of cell uptake behavior of SA11-PG10-C18 modified liposomes in vitro:

[0055] Flow cytometry was used to analyze the in vitro uptake of SA11-PG10-C18 modified liposomes by cells. Inflammatory activated neutrophils were incubated with fluorescently labeled SA11-PG10-C18 modified liposomes and fluorescently labeled ordinary liposomes for 30 minutes. For competitive inhibition experiments, cells were pretreated with excess sialic acid solution before incubating with fluorescently labeled SA11-PG10-C18 modified liposomes. After incubation, cells were centrifuged, fixed with 4% paraformaldehyde, and analyzed using a flow cytometer. The results are shown in Figure 2. Figure 7 As shown. Compared with ordinary liposomes, cells take up more SA11-PG10-C18 modified liposomes, which is manifested by a higher average fluorescence intensity in the group co-incubated with SA11-PG10-C18 modified liposomes. In addition, excessive sialic acid pretreatment will cause the fluorescence of SA11-PG10-C18 modified liposomes to be significantly weakened, indicating that sialic acid competitively inhibits the L-selectin receptor on the membrane of inflammatory activated neutrophils, thereby reducing the absorption of liposomes. These findings indicate that the specific binding of L-selectin to SA11-PG10-C18 modified on the surface of the preparation can promote the uptake of liposomes by cells.

[0056] Study on the anti-inflammatory effect of SA11-PG10-C18 modified liposomes:

[0057] 1) Investigation of the number of neutrophils in bronchoalveolar lavage fluid

[0058] At 0h, lipopolysaccharide was instilled into the mouse trachea to establish a mouse acute lung injury model. 4h later, curcumin preparation was intravenously injected. At 24h, the alveolar lavage fluid of the mice was collected to evaluate its therapeutic effect on inflammation. The results are as follows Figure 8 As shown. Inflammatory diseases are often accompanied by a large number of neutrophil infiltrations, and activated neutrophils play a key role in the development of inflammation. Compared with mice injected with PBS, the number of neutrophils in the bronchoalveolar lavage fluid after treatment with curcumin solution did not decrease significantly (P>0.05), while SA11-PG10-C18 modified liposome treatment showed the best effect of inhibiting neutrophil recruitment, which was manifested by a significant reduction in the infiltration of neutrophils into the lungs. Compared with the PBS-treated group, SA11-PG10-C18 modified liposomes effectively reduced the total number of neutrophils in the bronchoalveolar lavage fluid by 2.04 times. This effect is attributed to the modification of liposomes by SA11-PG10-C18, which enables SA11-PG10-C18 modified liposomes to preferentially target inflamed lungs rich in activated neutrophils, thereby specifically inhibiting the core disease process.

[0059] 2) Investigation of wet weight / dry weight ratio of mouse lungs

[0060] After 24 hours, the mice were euthanized and their lungs were collected. The blood on the surface of the lung lobe was absorbed with filter paper and the lung weight at this time was recorded as the wet weight (g); then the lungs were dried in a 60°C incubator for 48 hours and the lung weight at this time was recorded as the dry weight (g). The wet weight / dry weight ratio of the mouse lungs was calculated. The results are as follows: Fig. 9 As shown. Under the stimulation of inflammatory response, the wet weight / dry weight ratio of the mouse lung increased abnormally. After treatment with the preparation, the wet weight / dry weight ratio showed a decrease to varying degrees, among which the SA11-PG10-C18 modified liposome group had the most significant effect, indicating that the modification of liposomes by SA11-PG10-C18 can enhance the efficacy of the preparation. SA11-PG10-C18 modified liposomes can effectively stabilize the permeability of the alveolar capillary membrane and relieve pulmonary edema.

[0061] 3) Pathological section examination of mouse lungs

[0062] Mouse lung sections were stained with H&E and examined under a microscope. Fig.10As shown. After LPS induction, the lungs of mice in the PBS-treated group showed inflammatory characteristics, such as inflammation-induced bleeding (black arrow), pulmonary edema (green arrow), thickening of the alveolar septum (blue arrow), pulmonary vasodilation (yellow arrow), and accumulation of inflammatory cells in the alveoli or interstitium (red arrow), etc.; while in the SA11-PG10-C18-modified liposome-treated group, inflammatory cell infiltration was significantly reduced, alveolar patency was improved, and a healthy spongy lung structure was presented, further proving the excellent therapeutic effect of SA11-PG10-C18-modified liposomes on inflammatory diseases.

Claims

1. A polyglycerol fatty acid ester derivative SAm-PGn-HC containing a sialic acid group, characterized in that: The polyglycerol fatty acid ester derivative containing sialic acid groups, the carboxyl group on the sialic acid molecule is connected to the hydroxyl group on the polyglycerol fatty acid ester through an ester bond, and the structural formula is as follows: Wherein SA represents a sialic acid group, PG represents a polyglycerol monofatty acid ester fragment, HC represents a hydrocarbon chain, m represents the number of SA fragments grafted into the PG molecule, n represents the degree of polymerization of polyglycerol in the PG fragment, and x represents the number of carbon atoms in the hydrocarbon chain, 1≤m≤100, 1≤n≤100.

2. The polyglycerol fatty acid ester derivative SAm-PGn-HC containing a sialic acid group according to claim 1, characterized in that: 1≤m≤13, 1≤n≤12.

3. A polyglycerol fatty acid ester derivative SAm-PGn-HC containing a sialic acid group according to claim 1 or 2, characterized in that: The number of non-polar hydrocarbon chains in the PGn-HC is 1 to 3, which are 1 hydrocarbon chain, polyglycerol mono-fatty acid ester, 2 hydrocarbon chains, polyglycerol di-fatty acid ester, and 3 hydrocarbon chains, polyglycerol tri-fatty acid ester.

4. A polyglycerol fatty acid ester derivative SAm-PGn-HC containing a sialic acid group according to claim 3, characterized in that: The hydrocarbon chain of the PGn-HC is selected from one or more of caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, arachidonic acid, and oleic acid.

5. A method for synthesizing the polyglycerol fatty acid ester derivative SAm-PGn-HC containing sialic acid groups as claimed in any one of claims 1 to 4, characterized in that: The synthesis method comprises the following steps: 1) Under nitrogen protection, SA, PGn-HC, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride EDC and N-hydroxysuccinimide NHS are completely dissolved in anhydrous formamide, with EDC and NHS as catalysts, and stirred; 2) Add triethanolamine TEA dropwise to the reaction system and continue stirring; 3) After the reaction is completed, the product is placed in a dialysis bag, dialyzed in a dialysis medium, 80% of the water is removed by rotary evaporation, and the remaining solution is freeze-dried to obtain SAm-PGn-HC.

6. The preparation method according to claim 5, characterized in that: Step 1), in molar ratio, the content of -COOH in the SA structure: PGn-HC: EDC: NHS = 200:n:80:40, at which time the concentration of -COOH in the SA structure in the system is 1-571 mg / mL, the concentration of PGn-HC is 1-143 mg / mL, the concentration of EDC is 1-228 mg / mL, and the concentration of NHS is 1-114 mg / mL, and the stirring is carried out at 25°C for 30 min.

7. The preparation method according to claim 5, characterized in that: Step 2) After the triethanolamine TEA is dropped, the concentration of TEA in the system is 0.1-228 mg / mL, and the stirring time is 8 hours.

8. The preparation method according to claim 5, characterized in that: Step 3) The molecular weight cut-off of the dialysis bag is 10 kDa, the dialysis medium is distilled water, the dialysis time is to replace the dialysis medium every 4 hours, and the cumulative dialysis time is 24 hours.

9. Use of the polyglycerol fatty acid ester derivative SAm-PGn-HC containing sialic acid groups according to claim 1 in the preparation of pharmaceutical preparations.

10. The use according to claim 9, characterized in that The drug preparation is a microparticle drug delivery preparation, the SAm-PGn-HC is used for the preparation and modification of the microparticle drug delivery preparation, and the microparticle drug delivery preparation is micelle, liposome, vesicle, emulsion or nanoparticle.

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