Pdrn- spermidine co-delivery nanoliposome, and preparation method and application thereof

Abstract

The present application relates to the technical field of cosmetic biotechnology and nano-carrier drug delivery, and provides PDRN-putrescine co-delivery nano-liposome as well as a preparation method and application thereof.The PDRN-putrescine co-delivery nano-liposome provided by the present application comprises the following components in mass fraction: 0.1-3% of polydeoxyribonucleotide; 0.1-3% of putrescine; 2-8% of phospholipid emulsifier; 0-15% of polyhydric alcohol cosolvent; and the balance is a buffer solution; and the buffer solution has a pH value of 6-7.5.The present application realizes stable co-encapsulation of PDRN and putrescine by constructing a specific buffer system to regulate the pH value, using the amphiphilic property of the phospholipid bilayer and the in-situ ion pair technology, solves the compatibility problem of PDRN and putrescine, significantly improves the transdermal absorption rate of PDRN through transmembrane delivery of the nano-carrier, and realizes the synergistic repair and anti-aging effect of PDRN and putrescine at the cellular level.

Description

Technical Field

[0001] This invention relates to the fields of cosmetic biotechnology and nanocarrier drug delivery technology, and in particular to a PDRN-spermidine co-delivery nanoliposome, its preparation method and application. Background Technology

[0002] Polydeoxyribonucleotides (PDRN) are DNA fragments derived from salmon testes and possess significant tissue repair and anti-inflammatory functions. However, as a biomolecule with a large number of phosphate groups in its molecular structure, PDRN exhibits strong hydrophilicity and a high negative charge density. These physicochemical properties make it extremely difficult for PDRN to penetrate the lipid barrier of the stratum corneum of the skin, resulting in very low bioavailability and limiting its topical efficacy.

[0003] To address the transdermal challenges of PDRN, existing technologies primarily employ the following strategies, but all have shortcomings: (1) Physical permeation enhancement techniques (such as microneedling and radiofrequency): While these can significantly improve permeability, they are invasive or minimally invasive methods, accompanied by pain and a recovery period, making them unsuitable for daily skincare products. (2) Cationic liposomes (such as DOTAP and DC-Chol): These utilize synthesized cationic lipids to form complexes with DNA. Related patents report the use of cationic lipids to encapsulate nucleic acids, but synthesized cationic lipids often exhibit significant cytotoxicity and are prone to causing skin irritation, limiting their safety in cosmetic applications. (3) Cell-penetrating peptides (CPP): These utilize peptides such as TAT ​​to link PDRN. Although this method is effective, its synthesis cost is extremely high, and the peptides are easily degraded and inactivated in formulations.

[0004] PDRN is electronegative. Selecting suitable positively charged materials and using electrostatic interactions to bind with PDRN to form complexes is an effective approach to solving its transdermal challenges. Spermidine, a naturally occurring biopolyamine, carries a positive charge and has been shown to induce autophagy, exhibiting excellent anti-aging potential. Theoretically, combining spermidine with PDRN could allow spermidine to compress the DNA structure of PDRN, reducing its steric hindrance and neutralizing some of the negative charge, thereby improving PDRN's transdermal performance. However, current research on spermidine primarily focuses on oral anti-aging or single-component skin applications; there are no reports on its use as a nucleic acid carrier adjuvant.

[0005] Furthermore, PDRN is a polyanionic compound with a high density of negative charges, while spermidine is highly protonated under physiological pH conditions. When directly mixed in conventional cosmetic formulations, the two readily undergo a violent complexation reaction through strong electrostatic interactions, leading to flocculation of the active ingredients and the formation of large molecular aggregates (typically >1000nm) with uncontrollable particle size. This precipitation not only damages the product's appearance but also prevents the ingredients from being absorbed.

[0006] In summary, how to effectively co-load PDRN and spermidine to improve the transdermal absorption performance of PDRN is a problem that urgently needs to be solved in this field. Summary of the Invention

[0007] In view of this, the present invention provides a PDRN-spermidine co-delivery nanoliposome, its preparation method, and its application. The present invention utilizes the amphiphilicity of the phospholipid bilayer and in-situ ion-pairing technology to achieve stable co-encapsulation of PDRN and spermidine, significantly improving the transdermal absorption rate of PDRN and the synergistic repair and anti-aging effects of both at the cellular level.

[0008] To achieve the above-mentioned objectives, the present invention provides the following technical solution: A PDRN-spermidine co-delivery nanoliposome comprises the following components by mass fraction: Polydeoxyribonucleotides 0.1-3%; Spermine 0.1-3%; Phospholipid emulsifiers 2-8%; Polyol cosolvent 0~15%; The remainder is a buffer solution; the pH value of the buffer solution is 6~7.5.

[0009] Preferably, the mass ratio of the polydeoxyribonucleotide to spermidine is 1:10 to 10:1.

[0010] Preferably, the phospholipid emulsifier is selected from one or more of soybean lecithin, egg yolk lecithin, hydrogenated soybean lecithin, and hydrogenated egg yolk lecithin; The polyol cosolvent is selected from one or more of propylene glycol, butylene glycol, and glycerol; the average particle size of the PDRN-spermidine co-delivered nanoliposomes is 80~150 nm.

[0011] Preferably, the PDRN-spermidine co-delivery nanoliposomes further include 0.5-5% of a lipid membrane stabilizer, wherein the lipid membrane stabilizer comprises one or both of cholesterol and squalene.

[0012] This invention also provides a method for preparing the PDRN-spermidine co-delivered nanoliposomes described above, comprising the following steps: Polydeoxyribonucleotides and spermidine were dissolved in a buffer solution to obtain an aqueous phase; The organic phase is obtained by dissolving phospholipid emulsifiers in a polyol cosolvent, or by dissolving phospholipid emulsifiers and lipid film stabilizers in a polyol cosolvent. The organic phase was added to the aqueous phase and emulsified to obtain primary nanoliposomes; The primary nanoliposomes were stabilized to obtain the PDRN-spermidine co-delivery nanoliposomes.

[0013] Preferably, the emulsification is carried out under stirring or shearing conditions, wherein the stirring speed is 800~1500 rpm and the shearing rate is 3000~10000 rpm; The stabilization treatment is either a homogenization treatment or an ultrasonic treatment.

[0014] The present invention also provides the application of the PDRN-spermidine co-delivery nanoliposomes described in the above-described scheme or the PDRN-spermidine co-delivery nanoliposomes prepared by the preparation method described in the above-described scheme in cosmetics.

[0015] This invention also provides a cosmetic essence comprising PDRN-spermidine co-delivery nanoliposomes and cosmetically acceptable excipients; wherein the PDRN-spermidine co-delivery nanoliposomes are the PDRN-spermidine co-delivery nanoliposomes described in the above-described scheme or PDRN-spermidine co-delivery nanoliposomes prepared by the preparation method described in the above-described scheme; the cosmetically acceptable excipients include ion-resistant thickeners, wherein the ion-resistant thickeners include one or both of sclerotium gum and hydroxyethyl cellulose.

[0016] Preferably, the mass fraction of PDRN-spermidine co-delivered nanoliposomes in the cosmetic essence is 10-30%, and the mass fraction of ion-resistant thickener is 0.1-1%.

[0017] Preferably, the components include the following components by mass fraction: 10-30% PDRN-spermidine co-delivered nanoliposomes, 0.1-1% ion-resistant thickener, 2-7% glycerol, 0.5-1.5% 1,2-hexanediol, and the balance being deionized water.

[0018] This invention provides a PDRN-spermidine co-delivery nanoliposome, comprising the following components by mass fraction: 0.1-3% polydeoxyribonucleotides; 0.1-3% spermidine; 2-8% phospholipid emulsifier; 0-15% polyol co-solvent; and the balance being a buffer solution with a pH of 6-7.5. Addressing the technical challenge of PDRN and spermidine easily undergoing electrostatic complexation and flocculation in liquid systems due to charge differences, this invention constructs a specific buffer system to regulate the pH to 6-7.5. Utilizing the amphiphilicity of the phospholipid bilayer and in-situ ion-pairing technology, it achieves stable co-encapsulation of PDRN and spermidine, solving the compatibility problem between PDRN and spermidine. Simultaneously, through transmembrane delivery via nanocarriers, it significantly improves the transdermal absorption rate of PDRN and the synergistic repair and anti-aging effects of both at the cellular level.

[0019] The results of the examples show that the PDRN-spermidine co-delivery nanoliposomes provided by the present invention have the following beneficial effects: (1) Overcoming the taboos of the formulation: Successfully achieved the stable coexistence of high concentration of PDRN and spermidine, with no precipitation after 3 months of storage.

[0020] (2) Significantly improves transdermal absorption: Compared with ordinary mixtures, the PDRN-spermidine co-delivery nanoliposomes of the present invention significantly improve the transdermal absorption of PDRN.

[0021] (3) Synergistic effect: Cell experiments have shown that the PDRN-spermidine co-delivery nanoliposomes of the present invention achieve the co-delivery of PDRN and spermidine, and the cell proliferation rate is significantly higher than that of PDRN or spermidine alone. Attached Figure Description

[0022] Figure 1 The particle size distribution diagram is shown for the PDRN-spermidine co-delivered nanoliposomes prepared in Example 1. Figure 2 The appearance of the PDRN-spermidine co-delivered nanoliposomes prepared in Example 1. Detailed Implementation

[0023] This invention provides a PDRN-spermidine co-delivery nanoliposome, comprising the following components by mass fraction: Polydeoxyribonucleotides 0.1-3%; Spermine 0.1-3%; Phospholipid emulsifiers 2-8%; Polyol cosolvent 0~15%; The remainder is a buffer solution; the pH value of the buffer solution is 6~7.5.

[0024] Unless otherwise specified, all raw materials / components used in this invention are commercially available.

[0025] The PDRN-spermidine co-delivery nanoliposomes provided by the present invention, by mass fraction, include 0.1-3% polydeoxyribonucleotide (PDRN), specifically 0.1%, 0.3%, 0.4%, 0.5%, 1%, 2% or 3%; the molecular weight of the PDRN is preferably 20-50 kDa, specifically 23 kDa.

[0026] Based on mass fraction, the PDRN-spermidine co-delivery nanoliposomes provided by the present invention include 0.1-3% spermidine, specifically 0.1%, 0.3%, 0.4%, 0.5%, 1%, 2% or 3%; the mass ratio of the polydeoxyribonucleotide to spermidine is preferably 1:10-10:1, specifically 1:1.

[0027] By mass fraction, the PDRN-spermidine co-delivered nanoliposomes provided by the present invention include 2-8% phospholipid emulsifiers, specifically 2%, 4%, 5%, 6% or 8%; the phospholipid emulsifiers are preferably selected from one or more of soybean lecithin, egg yolk lecithin, hydrogenated soybean lecithin and hydrogenated egg yolk lecithin.

[0028] The PDRN-spermidine co-delivery nanoliposomes provided by the present invention, by mass fraction, comprise 0-15% polyol co-solvent, preferably greater than 0 and less than or equal to 15%, specifically 1%, 5%, 9%, 10%, 12% or 15%; the polyol co-solvent is preferably selected from one or more of propylene glycol, butanediol and glycerol, and the propylene glycol may specifically be 1,2-propanediol or 1,3-propanediol.

[0029] The components of the PDRN-spermidine co-delivered nanoliposomes preferably further include 0.5-5% lipid membrane stabilizer by mass fraction, specifically 0.5%, 1%, 2%, 3% or 5%; the lipid membrane stabilizer preferably includes one or both of cholesterol and squalene; in this invention, the lipid membrane stabilizer helps to enhance the stability of the liposome membrane and improve the physical properties of the liposomes such as fluidity and thermal stability.

[0030] The PDRN-spermidine co-delivery nanoliposomes provided by the present invention, by mass fraction, include a buffer solution in the remainder, wherein the pH value of the buffer solution is preferably 6 to 7.5, specifically 6.8 or 7.2; the buffer solution is preferably phosphate buffer solution (PBS).

[0031] This invention reveals that under specific pH (6-7.5) and ionic strength conditions, the electrostatic binding force between PDRN and spermidine is within a controllable range. When an amphiphilic phospholipid emulsifier is introduced, spermidine can act as a counterion to bind orderly with the phosphate backbone of PDRN, compressing the spatial conformation of PDRN. This not only avoids precipitation but also increases the drug loading rate within the hydrophilic core of the liposome, resulting in a stable system with uniform particle size.

[0032] In this invention, the average particle size of the PDRN-spermidine co-delivered nanoliposomes is 80~150nm, and in the examples it is 105.6nm or 120.4nm; the PDI value of the PDRN-spermidine co-delivered nanoliposomes is ≤0.2, and in the examples it is 0.17 and 0.19.

[0033] This invention also provides a method for preparing the PDRN-spermidine co-delivered nanoliposomes described above, comprising the following steps: Polydeoxyribonucleotides and spermidine were dissolved in a buffer solution to obtain an aqueous phase; The organic phase is obtained by dissolving phospholipid emulsifiers in a polyol cosolvent, or by dissolving phospholipid emulsifiers and lipid film stabilizers in a polyol cosolvent. The organic phase was added to the aqueous phase and emulsified to obtain primary nanoliposomes; The primary nanoliposomes were stabilized to obtain the PDRN-spermidine co-delivery nanoliposomes.

[0034] In this invention, polydeoxyribonucleotides and spermidine are dissolved in a buffer solution to obtain an aqueous phase. This invention does not have special requirements for the dissolution conditions; stirring is sufficient until the solution is clear, transparent, and free of flocculation.

[0035] This invention dissolves phospholipid emulsifiers in a polyol co-solvent, or dissolves phospholipid emulsifiers and lipid film stabilizers in a polyol co-solvent to obtain an organic phase. The dissolution is preferably carried out under heating conditions; however, this invention does not have specific requirements for the heating conditions, as long as complete dissolution is achieved.

[0036] After obtaining the aqueous phase and the organic phase, the present invention adds the organic phase to the aqueous phase for emulsification to obtain primary nanoliposomes. In the present invention, when the organic phase is added to the aqueous phase for emulsification, the temperature of the organic phase is preferably controlled at 25~65℃, specifically 30℃.

[0037] In this invention, the emulsification is preferably carried out under stirring or shearing conditions. The stirring speed is preferably 800-1500 rpm, specifically 1000 rpm, and the shearing rate is preferably 3000-10000 rpm. In a specific embodiment of this invention, the organic phase is preferably slowly injected into the aqueous phase under stirring or shearing conditions, and emulsification continues under stirring or shearing conditions after injection is complete. The injection rate of the organic phase can be 2 mL / min; the emulsification time can be 30 min, and the emulsification time is counted from the completion of the organic phase injection.

[0038] After obtaining the primary nanoliposomes, the present invention stabilizes the primary nanoliposomes to obtain the PDRN-spermidine co-delivered nanoliposomes. In this invention, the stabilization treatment is either homogenization or ultrasonication; the homogenization pressure is preferably 2000-3000 psi, specifically 2500 psi, and the number of cycles is preferably 3; the ultrasonication power is preferably 50-200 W, specifically 50 W or 100 W, and the treatment time is preferably 5-10 min. This invention controls the particle size of the final obtained PDRN-spermidine co-delivered nanoliposomes through the stabilization treatment.

[0039] In this invention, the PDRN-spermidine co-delivered nanoliposomes are semi-transparent nanoliposome dispersions with a blue opalescent luster.

[0040] This invention also provides the application of the PDRN-spermidine co-delivery nanoliposomes described in the above scheme or the PDRN-spermidine co-delivery nanoliposomes prepared by the preparation method described in the above scheme in cosmetics; the cosmetics may specifically be cosmetic essences.

[0041] This invention also provides a cosmetic essence comprising PDRN-spermidine co-delivery nanoliposomes and cosmetically acceptable excipients; wherein the PDRN-spermidine co-delivery nanoliposomes are the PDRN-spermidine co-delivery nanoliposomes described in the above scheme or the PDRN-spermidine co-delivery nanoliposomes prepared by the preparation method described in the above scheme; the cosmetic essence provided by this invention is specifically a cosmetic essence with high penetration and repair effects.

[0042] In this invention, the cosmetically acceptable excipients include ion-resistant thickeners, which are preferably selected from one or both of sclerotinia gum and hydroxyethyl cellulose.

[0043] In this invention, the cosmetically acceptable excipients preferably also include glycerin and 1,2-hexanediol.

[0044] In this invention, the mass fraction of PDRN-spermidine co-delivered nanoliposomes in the cosmetic essence is preferably 10-30%, specifically 10%, 15%, 20% or 30%; the mass fraction of ion-resistant thickener in the cosmetic essence is preferably 0.1-1%, specifically 0.5%.

[0045] In this invention, the cosmetic essence preferably comprises the following components by mass fraction: 10-30% PDRN-spermidine co-delivered nanoliposomes, 0.1-1% ion-resistant thickener, 2-7% glycerol, 0.5-1.5% 1,2-hexanediol, and the balance being deionized water; in a specific embodiment of this invention, the mass fraction of glycerol in the cosmetic essence is preferably 5%, and the mass fraction of 1,2-hexanediol is preferably 5%.

[0046] In this invention, the preferred method for preparing the cosmetic essence includes the following steps: dispersing an ion-resistant thickener in glycerin for wetting, then adding deionized water for swelling to form a gel matrix; adding the PDRN-spermidine co-delivery nanoliposomes to the gel matrix, stirring evenly, and then adding 1,2-hexanediol to obtain the cosmetic essence.

[0047] The technical solutions of this invention will be clearly and completely described below with reference to the embodiments thereof. Obviously, the described embodiments are only a part of the embodiments of this invention, and not all of them. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.

[0048] The molecular weight of PDRN used in the following examples is 23 kDa.

[0049] Example 1: Preparation of PDRN-spermidine co-delivered nanoliposomes (1) Aqueous phase: Weigh 0.5g of PDRN powder and 0.5g of spermidine, and dissolve them in 90g of phosphate buffer (PBS) at pH 6.8. Stir and observe. The solution is clear and transparent, without flocculation, and the aqueous phase is obtained.

[0050] (2) Organic phase: Weigh 5.0g of soybean lecithin, dissolve it in 10g of 1,2-propanediol, heat to 30℃ and stir until clear to obtain the organic phase.

[0051] (3) Preparation: The organic phase was injected into the aqueous phase at a rate of 2 mL / min, and magnetic stirring was started at 1000 rpm. After mixing, stirring was continued for 30 minutes to obtain primary liposomes.

[0052] (4) Stabilization treatment: The primary liposomes were subjected to ultrasonic treatment with an ultrasonic power of 50W and a treatment time of 10min to obtain a semi-transparent nanoliposome dispersion with a blue opalescence.

[0053] Comparative Example 1: Direct mixing of ordinary aqueous solutions 0.5g of PDRN and 0.5g of spermidine were directly dissolved in 100g of deionized water (without buffering capacity and a natural pH of approximately 8.5), without the addition of phospholipids. The results showed that a large amount of white flocculent precipitate was formed instantly upon mixing of PDRN and spermidine, and it could not be reconstituted.

[0054] Comparative Example 2: Preparation of PDRN-spermidine co-delivery nanoliposomes at different pH values The only difference from Example 1 is that the pH value of the buffer solution used is 4.0, while the rest of the steps are the same.

[0055] The results showed that the obtained emulsion was milky white and turbid, and after standing for 24 hours, a layer of sediment appeared at the bottom.

[0056] Comparative Example 3: Single-component liposomes (without spermidine) The only difference from Example 1 is that spermidine is not added, and only PDRN liposomes are prepared.

[0057] Example 2: Preparation of nanoliposomes with different ratios and phospholipid types To verify the applicability of this invention under different formulation parameters, nanoliposomes were prepared using phospholipids of different proportions and types. Formulation composition: PDRN: 1.0g; spermidine: 1.0g (PDRN and spermidine mass ratio 1:1); hydrogenated soybean lecithin (HSPC): 6.0g; cholesterol: 1.0g; 1,3-propanediol: 12.0g; pH 7.2 phosphate buffer: balance to 100g.

[0058] Preparation process: (1) Dissolve PDRN and spermidine in buffer solution and stir for 30 min to form a homogeneous aqueous phase.

[0059] (2) Dissolve hydrogenated soybean lecithin and cholesterol in 1,3-propanediol and heat to 60°C (because the phase transition temperature of hydrogenated soybean lecithin is high, it needs to be heated appropriately to dissolve, but the temperature is lowered to 35°C when it is injected) to obtain the organic phase.

[0060] (3) While stirring at 1000 rpm, the organic phase was injected into the aqueous phase at a rate of 3 mL / min.

[0061] (4) The mixture was processed by a high-pressure homogenizer (2500 psi, 3 cycles).

[0062] Results: The prepared liposomes had an average particle size of 105.6 nm, a PDI of 0.19, a translucent light blue appearance, and a Zeta potential of -12.5 mV. This example demonstrates that adjusting the PDRN to spermidine ratio to 1:1 and using hydrogenated soybean lecithin can also yield high-quality nanoliposomes.

[0063] Example 3: Cosmetic essence with high penetration and repair effects This embodiment demonstrates the application of nanoliposomes in a practical cosmetic formulation, focusing on their compatibility with ionic thickeners. The formulation of the cosmetic serum in this embodiment is shown in Table 1.

[0064] Table 1. Cosmetic Essence Formula

[0065] The preparation method of cosmetic essence is as follows: First, disperse sclerotium gum in glycerin to moisten it, add deionized water and homogenize to swell, forming a transparent gel matrix (phase B). Slowly add phase A to phase B, stir at low speed until homogeneous, then add phase C and stir until homogeneous to obtain the final product.

[0066] Description of properties: The resulting essence is a semi-transparent fluid with a silky texture and a pH value maintained at around 6.5.

[0067] Comparative Explanation: If sclerotinia gum is replaced with ordinary carbomer, the carbomer will instantly lose its activated water due to the presence of buffer salt ions and the positive charge of spermidine in the system, resulting in a sharp drop in viscosity and stratification. This example demonstrates the necessity of using nonionic / ion-resistant thickeners such as sclerotinia gum.

[0068] Test case 1. Physicochemical properties and stability tests The particle size and PDI of the nanoliposomes obtained in Example 1 and Comparative Examples 1-3 were determined using a Malvern particle size analyzer, and their stability was observed after 30 days. The results are shown in Table 2, where the particle size distribution of the PDRN-spermidine co-delivered nanoliposomes prepared in Example 1 is shown in the figure. Figure 1 As shown, the appearance is as follows Figure 2 As shown.

[0069] Table 2. Results of particle size, PDI, and stability tests

[0070] The results in Comparative Example 1 show that direct mixing of PDRN and spermidine results in severe physical incompatibility. The results in Example 1 demonstrate that the present invention can effectively solve the compatibility problem between PDRN and spermidine by preparing PDRN-speridine co-delivery nanoliposomes under specific pH buffer conditions, and obtain a stable and uniform nanoliposome system.

[0071] 2. In vitro transdermal permeation experiment To verify the promoting effect of the nanoliposomes of the present invention on the transdermal absorption of PDRN, an in vitro transdermal experiment was conducted using the Franz diffusion cell method.

[0072] Experimental material: Ex vivo back skin of Bama pigs (subcutaneous fat removed, epidermis and dermis retained).

[0073] Experimental Groups: Group A: Example 1 (Nanoliposomes of the present invention); Group B: Comparative Example 3 (conventional PDRN liposomes, without spermidine); Group C: PDRN aqueous solution (control group); Experimental Method: The receiving cell was filled with PBS (pH 7.4) and kept at a constant temperature of 37℃. Equal amounts of samples from each group (containing the same total PDRN content) were applied to the stratum corneum of the skin. Samples were taken at 4h, 12h, and 24h, and the PDRN content retained in the receiving solution and skin layer was detected by HPLC. The test results are shown in Table 3.

[0074] Table 3 Results of 24-hour in vitro transdermal penetration

[0075] 3. Cell proliferation rate Human skin fibroblasts (HSF) were used, and cell proliferation rate was determined using the CCK-8 assay. Specific testing conditions were as follows: Cell seeding concentration: 5 × 10⁶ cells per well. 4 HSF cells were cultured in 24-well plates. The concentration of nanoliposomes added was 10 µg / mL in Example 1 and 10 µg / mL in Comparative Example 3. Cell culture conditions: cultured at 37°C in a 5% CO2 incubator for 24 hours. The test results are shown in Table 4.

[0076] Table 4. Results of cell proliferation rate test

[0077] As can be seen from the results in Table 4, the cell proliferation rate of the nanoliposomes in Example 1 was significantly higher than that in Comparative Example 3, proving that encapsulating PDRN and spermidine in the same nanocarrier can produce an unexpected synergistic repair effect. This may be related to spermidine activating autophagy, thereby enhancing the uptake and utilization of PDRN by cells.

[0078] In summary, the PDRN-spermidine co-delivery nanoliposomes provided by this invention solve the electrostatic incompatibility problem between PDRN and spermidine, and achieve synergistic effects between the two, thus having broad application prospects.

[0079] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A PDRN-spermidine co-delivery nanoliposome, characterized in that, Components including the following mass fractions: Polydeoxyribonucleotides 0.1-3%; Spermine 0.1-3%; Phospholipid emulsifiers 2-8%; Polyol cosolvent 0~15%; The remainder is a buffer solution; the pH value of the buffer solution is 6~7.

5.

2. The PDRN-spermidine co-delivered nanoliposomes according to claim 1, characterized in that, The mass ratio of the polydeoxyribonucleotide to spermidine is 1:10 to 10:

1.

3. The PDRN-spermidine co-delivery nanoliposomes according to claim 1, characterized in that, Phospholipid emulsifiers are selected from one or more of soybean lecithin, egg yolk lecithin, hydrogenated soybean lecithin, and hydrogenated egg yolk lecithin; The polyol cosolvent is selected from one or more of propylene glycol and butylene glycol; The average particle size of the PDRN-spermidine co-delivered nanoliposomes is 80~150 nm.

4. The PDRN-spermidine co-delivered nanoliposomes according to claim 1, characterized in that, The components of the PDRN-spermidine co-delivered nanoliposomes also include 0.5-5% of a lipid membrane stabilizer, which includes one or both of cholesterol and squalene.

5. The method for preparing PDRN-spermidine co-delivered nanoliposomes according to any one of claims 1 to 4, characterized in that, Includes the following steps: Polydeoxyribonucleotides and spermidine were dissolved in a buffer solution to obtain an aqueous phase; The organic phase is obtained by dissolving phospholipid emulsifiers in a polyol cosolvent, or by dissolving phospholipid emulsifiers and lipid film stabilizers in a polyol cosolvent. The organic phase was added to the aqueous phase and emulsified to obtain primary nanoliposomes; The primary nanoliposomes were stabilized to obtain the PDRN-spermidine co-delivery nanoliposomes.

6. The preparation method according to claim 5, characterized in that, The emulsification is carried out under stirring or shearing conditions, wherein the stirring speed is 800~1500 rpm and the shearing rate is 3000~10000 rpm. The stabilization treatment is either a homogenization treatment or an ultrasonic treatment.

7. The application of the PDRN-spermidine co-delivered nanoliposomes according to any one of claims 1 to 4 or the PDRN-spermidine co-delivered nanoliposomes prepared by the preparation method according to any one of claims 5 to 6 in cosmetics.

8. A cosmetic essence, characterized in that, The invention includes PDRN-spermidine co-delivery nanoliposomes and cosmetically acceptable excipients; the PDRN-spermidine co-delivery nanoliposomes are the PDRN-spermidine co-delivery nanoliposomes according to any one of claims 1 to 4 or the PDRN-spermidine co-delivery nanoliposomes prepared by the preparation method according to any one of claims 5 to 6; the cosmetically acceptable excipients include ionic thickeners, and the ionic thickeners include one or two of sclerotium gum and hydroxyethyl cellulose.

9. The cosmetic essence according to claim 8, characterized in that, The cosmetic essence contains 10-30% PDRN-spermidine co-delivered nanoliposomes and 0.1-1% ionic thickener.

10. The cosmetic essence according to claim 8 or 9, characterized in that, The product comprises the following components by mass fraction: 10-30% PDRN-spermidine co-delivered nanoliposomes, 0.1-1% ion-resistant thickener, 2-7% glycerol, 0.5-1.5% 1,2-hexanediol, and the balance being deionized water.

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