CN-122005690-A - Liposome containing natural extract composition and preparation method and application thereof

CN122005690ACN 122005690 ACN122005690 ACN 122005690ACN-122005690-A

Abstract

The invention belongs to the technical field of biological medicines, and particularly discloses a liposome containing a natural extract composition, and a preparation method and application thereof. The method for preparing liposome containing natural extract composition comprises S1 adding organic solvent into grape, poria, apple extract, cholesterol and lecithin, heating and stirring to dissolve to obtain organic phase, and adding ultrapure water into soybean and Ginseng radix extract, heating and stirring to obtain water phase. S2, slowly adding the organic phase into the water phase under stirring, continuously stirring and emulsifying, and removing the organic solvent by reduced pressure distillation to obtain a liposome suspension. S3, filtering the suspension, adding a freeze-drying protective agent, and freeze-drying to obtain the liposome. The invention also covers the use of said liposomes in the treatment of renal failure. In the present disclosure, the synergistic effect of the components is produced by combining natural extracts and administering the combination of liposomes in specific compositions, which has remarkable therapeutic effects on renal failure, especially chronic renal failure.

Inventors

TANG YUXIANG
HU HANG

Assignees

宇科生物(武汉市)有限责任公司

Dates

Publication Date: 20260512
Application Date: 20260310

Claims (10)

1. A method for preparing a composition liposome containing a natural extract, comprising the steps of: s1, adding grape extract, poria cocos extract and apple extract, adding cholesterol and lecithin into an organic solvent, heating, stirring and dissolving to obtain an organic phase, adding soybean extract and ginseng extract into ultrapure water, and heating and stirring uniformly to obtain a water phase; s2, adding the organic phase into the water phase, stirring while adding, continuing stirring and emulsifying after the addition is completed, and distilling under reduced pressure to remove the organic solvent to obtain liposome suspension; S3, filtering the liposome suspension, adding a freeze-drying protective agent into the filtrate, and freeze-drying to obtain a natural extract composition-containing liposome; The grape extract, the soybean extract, the poria cocos extract, the apple extract and the ginseng extract are in a mass ratio of 1 to 2 to 1 to 2, and the natural extract composition, the lecithin, the cholesterol and the freeze-drying protective agent are in a mass ratio of 1 to 2.5 to 5 to 0.3 to 1 to 3.2 to 5, wherein the mass of the natural extract composition is calculated by the mass sum of the grape extract, the soybean extract, the poria cocos extract, the apple extract and the ginseng extract.
2. The method of claim 1, wherein the grape extract is a kangfu grape extract, the poria cocos extract is Jin Run poria cocos extract, the apple extract is a youpeptide apple extract, the soybean extract is a source-picked soybean extract, and the ginseng extract is a source-picked ginseng extract.
3. The preparation method of the liposome containing the natural extract composition according to claim 1, wherein the mass ratio of grape extract, soybean extract, poria cocos extract, apple extract and ginseng extract is 1:1:1:1:2, the mass ratio of the natural extract composition, lecithin, cholesterol and lyoprotectant is 1:2.5:0.5:2.5, the volume ratio of organic solvent to aqueous phase in S2 is 1 (1-2), and the lyoprotectant with the same mass as lecithin is added in S3.
4. The method for preparing liposome containing natural extract composition according to claim 3, wherein the organic solvent in S1 is any one of ethanol, tetrahydrofuran, acetone or methanol, preferably ethanol, and the lyoprotectant in S3 is any one of glucose, sucrose and sorbitol, preferably glucose.
5. The method for preparing a liposome containing a natural extract composition according to claim 1, wherein in the step S2, the reaction temperature of stirring emulsification is 30-80 ℃, preferably 40 ℃ and the reaction time is 1-11 h, the reaction time can be adaptively adjusted according to the emulsification degree, preferably 5h, the step S3, the freeze-drying comprises the steps of pre-freezing at-80 ℃ for 2-6 h, then freeze-drying at-15 ℃ for 1-4 h, and filtering the liposome suspension through a filter membrane with the pore diameter of 0.22 μm during the filtration.
6. The natural extract composition-containing liposome prepared by the method for preparing a natural extract composition-containing liposome of any one of claims 1 to 5.
7. Use of a liposome containing a natural extract composition in the preparation of a medicament for treating renal failure in pets.
8. The method according to claim 7, wherein the drug for treating renal failure in pets is a drug for treating chronic renal failure in pets.
9. Use of a liposome comprising a natural extract composition for reducing the severity of renal failure in an animal model of renal failure, wherein the severity of renal failure in the animal model of renal failure is any of: Reducing the expansion degree of the renal tubules; Reduce tubular epithelial cell necrosis; reducing infiltration of interstitial inflammatory cells; alleviating renal atrophy.
10. The method according to claim 9, wherein the animal model of renal failure is a chronic animal model of renal failure.

Description

Liposome containing natural extract composition and preparation method and application thereof Technical Field The invention belongs to the technical field of biological medicines, and particularly relates to a liposome containing a natural extract composition, and a preparation method and application thereof. Background Renal failure (chronic renal failure, CRF) is a substantial damage to the kidneys caused by destruction of the nephron structure, loss of function, and the like, caused by a variety of factors (e.g., diabetes, hypertension, glomerulonephritis, etc.). Chronic renal failure is a major feature of metabolites, water, electrolytes, acid-base disorders and renal atrophy, an important public health problem worldwide. When part of the nephrons are necrotic, the residual nephrons have a greater degree of dilation into the glomerular arterioles than out of the glomerular arterioles, resulting in increased pressure in the glomerular capillaries (high pressure), and increased blood flow (high perfusion). This high pressure state can damage glomerular basement membrane, leading to proliferation of mesangial cells, increased stroma, further triggering oxidative stress, inflammatory response and cytokine release (especially TGF- β1), and eventually glomerulosclerosis. Once one glomerulus hardens, the remaining nephrons are more heavily burdened, forming a vicious circle, causing severe renal fibrosis. Currently, the core strategies for treating renal failure mainly include the use of Angiotensin Converting Enzyme Inhibitors (ACEI) and angiotensin II receptor Antagonists (ARBs), the strict control of blood pressure, low protein diets, SGLT2 inhibitors, and the like. These means delay the deterioration of renal function and improve renal prognosis by diuretic and antihypertensive actions. In addition to the above, some studies have reported that some plant extracts (such as grape extract, soybean extract, poria extract, apple extract, ginseng extract, etc.) also have some improving effect on some kidney disease models, however, the mechanism of action is different from that of the target disorder. For example, the apple extract is taken as an example, the existing research shows that the apple extract is discharged after being combined with urinary toxins and excessive phosphorus and potassium in intestinal tracts, so that the damage caused by kidney excretion load and toxin accumulation is reduced, but the extract is difficult to directly act on kidney cells, and inflammation and necrosis pathways cannot be obviously inhibited. The scheme of treating renal failure by using natural extracts is imperfect, and although more natural extracts are initially verified to have a regulating effect, the effect is not ideal after in vivo experiments are carried out, and no natural extract medicine capable of playing an effective role in treating renal failure of animals exists at present. In our earlier studies, it was unexpectedly found that although apple extract alone had little improvement in renal failure, the therapeutic effect was significantly enhanced after compounding with extracts of grape, soybean, poria and ginseng, especially when apple extract was present in a higher proportion than the other components in the compounding system. This suggests that apple extract may act synergistically with other ingredients at a specific compounding ratio, thereby more effectively inhibiting the progression of renal failure. Based on the unexpected findings, we further explored the effect of different extract ratios on the therapeutic effect. Furthermore, in order to optimize the in vivo distribution behavior of the drug and to enhance the therapeutic effect, we tried to encapsulate the complex extract in liposomes for administration. However, the research results show that compared with the common water aqua, the liposome drug-loading mode does not show better treatment effect under all compound ratios, and the effect is obviously dependent on the specific composition of the composition. Notably, while the prior literature suggests that soybean extract may be one of the aforementioned natural ingredients that have the greatest potential for alleviating renal failure, in this study, it appears that the efficacy of the extract when administered in liposome form is significantly lower than that of the aqueous formulation of the five extract complexes, suggesting that the simple combination of "extract with optimal renal failure improving effect alone + liposome optimization" does not necessarily produce better results. Therefore, it is believed that while liposomes as a drug delivery system can enhance drug bioavailability and targeting in most cases, their efficacy is not universally enhanced when combined with the multicomponent plant extract complex systems employed in this study, and need to be systematically evaluated and optimized depending on the specific compounding ratios. Disclosure of Invention In order to sol