Anti-inflammatory and repairing heparin sodium liposome gel and preparation method thereof

Abstract

The invention belongs to the field of cosmetic preparation, and particularly relates to anti-inflammatory and repairing heparin sodium liposome gel and a preparation method thereof. The heparin sodium liposome gel disclosed by the invention is prepared from the following components in percentage by mass: 1.0 to 3.0 percent of heparin sodium liposome, 11.8 to 14.1 percent of a humectant, 0.2 to 0.5 percent of triethanolamine, 0.3 to 0.7 percent of a thickening agent, 0.1 to 0.2 percent of a preservative, 0.1 to 0.2 percent of essence and the balance of water. Natural raw materials such as soybean lecithin and phytosterol are adopted, and carboxymethyl chitosan and polyethylene glycol are combined to optimize a membrane structure, so that the transdermal efficiency and the anti-inflammatory effect of heparin sodium are remarkably improved; a plurality of humectants (propylene glycol, glycerol, betaine and the like) are added, so that the skin barrier can be repaired, and good stability, moisture retention, anti-inflammation and repairing effects are achieved.

Description

Technical Field

[0001] The invention belongs to the field of cosmetic preparation, and particularly relates to an anti-inflammatory and repairing heparin sodium liposome gel and a preparation method thereof. Background Art

[0002] In modern society, skin inflammation (such as contact dermatitis, acne, and postoperative repair) and injuries (such as burns and post-laser surgery) are common clinical problems. Traditional treatments often rely on hormone-based drugs or chemically synthesized anti-inflammatory agents, but long-term use can cause side effects such as skin atrophy and hormone dependency. Therefore, the development of safe and effective natural or biocompatible anti-inflammatory and repair products has become a research hotspot.

[0003] Heparin sodium is a glycosaminoglycan, traditionally used for anticoagulant therapy. However, recent studies have found that it has significant anti-inflammatory activity, can inhibit inflammatory mediators, and by binding to inflammatory factors (such as TNF-α, IL-6) and chemokines, block the inflammatory cascade reaction; promote wound healing, accelerate epidermal cell proliferation, inhibit scar formation, and improve tissue repair. Patent CN103356693A discloses a compound low molecular weight heparin sodium liposome gel, the raw materials of which include low molecular weight heparin sodium, asiaticoside, lipid components, membrane softeners, and gel matrix components, wherein low molecular weight heparin sodium and asiaticoside are pharmacologically active ingredients. The preparation method and steps are as follows: (1) preparing compound low molecular weight heparin sodium liposomes by ethanol injection-ultrasound method or ethanol injection-high pressure homogenizer method; (2) preparing a blank gel; (3) adding the compound low molecular weight heparin sodium liposomes to the blank gel and stirring evenly to obtain the compound low molecular weight heparin sodium liposome gel. The gel of the invention is mainly used to treat skin injuries and scars. However, heparin sodium has strong water solubility and low transdermal absorption rate, which limits its application in local skin treatment.

[0004] Liposomes, as nanoscale carriers, can encapsulate drugs and improve transdermal efficiency, with the following benefits: (1) Targeted delivery: penetrating the skin barrier through the phospholipid bilayer structure, concentrating heparin sodium at the site of inflammation; (2) Sustained release: prolonging the duration of drug action and reducing the need for frequent dosing; (3) Reducing irritation: encapsulating polar molecules, reducing direct irritation to the skin. However, traditional liposome preparation often uses synthetic materials, which lack biocompatibility and have poor stability.

[0005] Currently available anti-inflammatory products have problems such as insufficient permeability, single ingredients, and safety risks. Therefore, the development of an effective and safe anti-inflammatory product has broad clinical and market application value. Summary of the Invention

[0006] The present invention discloses an anti-inflammatory and repairing heparin sodium liposome gel. The gel adopts natural raw materials such as soybean lecithin and phytosterols, combines carboxymethyl chitosan and polyethylene glycol to optimize the membrane structure, and significantly improves the transdermal efficiency and anti-inflammatory effect of heparin sodium. The gel also adds a variety of moisturizers (propylene glycol, glycerol, betaine, etc.) to repair the skin barrier, and has good stability, moisturizing power, anti-inflammatory and repairing effects.

[0007] To achieve the above object, the technical solution adopted by the present invention is as follows:

[0008] The first aspect of the present invention provides an anti-inflammatory and repairing heparin sodium liposome gel, which comprises the following components in percentage by mass:

[0009] Heparin sodium liposome 1.0-3.0%, moisturizer 11.8-14.1%, triethanolamine 0.2-0.5%, thickener 0.3-0.7%, preservative 0.1-0.2%, flavor 0.1-0.2%, and the balance is water.

[0010] In some embodiments, the moisturizing agent includes propylene glycol 4.5-5.0%, glycerin 5.5-6.5%, 1,3-butylene glycol 0.3-0.6% and betaine 1.5-2.0%.

[0011] In some embodiments, the preparation method of the heparin sodium liposome is:

[0012] (1) Dispersing soybean lecithin in deionized water and stirring in a water bath to obtain liquid 1; dissolving phytosterol in ethanol and ultrasonicating to obtain liquid 2; dispersing carboxymethyl chitosan and polyethylene glycol in deionized water and stirring in a water bath until clear to obtain liquid 3; adding liquid 1, liquid 2, and liquid 3 into a container in sequence and homogenizing to form an oil-in-water microemulsion;

[0013] (2) adding heparin sodium to the oil-in-water microemulsion of step (1), continuing homogenization, ultrasonicating in an ice bath, and then adding a natural protective agent to the mixture, stirring evenly, adjusting the pH, and sterilizing and filtering to obtain heparin sodium liposomes.

[0014] In some embodiments, in step (1), the number average molecular weight of carboxymethyl chitosan is 5,000-50,000, and the number average molecular weight of polyethylene glycol is 2,000-10,000.

[0015] In some embodiments, the mass ratio of soybean lecithin, phytosterol, carboxymethyl chitosan and polyethylene glycol in the oil-in-water microemulsion in step (1) is (4-6):(1-2):(0.5-1):1.

[0016] In some embodiments, the amount of heparin sodium added in step (2) is 1-2.5 wt % of the oil-in-water microemulsion.

[0017] In some embodiments, the natural protective agent in step (2) includes sodium hyaluronate, trehalose and vitamin E; the amount of the natural protective agent is 1-5 wt % of the mixture.

[0018] In some embodiments, the component further comprises 0.5-2.0% of a polyquaternium salt complex, calculated by mass percentage.

[0019] In some embodiments, the preparation method of the polyquaternium salt complex is:

[0020] S1: Add polyquaternium-51 to deionized water, stir until dissolved, and adjust the pH to 6.5-7.0 to obtain solution 1;

[0021] S2: Add glutamic acid to deionized water, stir until dissolved, and adjust the pH to 8.0-9.0 to obtain solution 2;

[0022] S3: Solution 2 is added dropwise to solution 1, stirred for 1-2 hours, and then disodium EDTA is added thereto, stirred, and dried to obtain a polyquaternary ammonium salt complex.

[0023] In some embodiments, the mass ratio of the polyquaternium-51 to glutamic acid is 1:(0.5-2).

[0024] The second aspect of the present invention provides a method for preparing the heparin sodium liposome gel described in the above scheme, comprising the following steps:

[0025] (1) Step 1: Take a preservative, add it to propylene glycol at 50-60°C, and stir to dissolve; then add a thickener and part of the water to make the thickener swell and disperse to obtain solution 1, and keep it warm for later use;

[0026] (2) Step 2: Take the remaining water, add betaine, and stir at 50-60°C until dissolved; then add heparin sodium liposomes and stir; add glycerol and 1,3-butanediol and stir to dissolve to obtain solution 2, which is kept warm for later use;

[0027] (3) Step 3: Add solution 2 to solution 1 at 30-45°C and stir evenly; add triethanolamine to adjust the pH to 6.5-7.5; stir; under stirring, cool to 25-30°C, add flavoring, stir, and fill to obtain heparin sodium liposome gel.

[0028] In order to improve the anticoagulant and anti-inflammatory effects of sodium heparin, the present invention uses soybean lecithin and phytosterol as main materials, and adds carboxymethyl chitosan and polyethylene glycol. Carboxymethyl chitosan has good water solubility and certain film-forming properties, and polyethylene glycol plays a role in regulating the viscosity of the system and enhancing the dispersibility. Carboxymethyl chitosan and polyethylene glycol are intertwined with soybean lecithin and phytosterol through intermolecular forces, and together construct a stable oil-in-water microemulsion system during the homogenization process; sodium heparin is then added thereto and wrapped into the aqueous phase region inside the liposome; then a natural protective agent composed of sodium hyaluronate, trehalose and vitamin E is added, and sodium hyaluronate can form a The hydration film prevents liposomes from aggregating and helps enhance the affinity of liposomes to the skin. Trehalose has good glass transition properties and can form a stable glassy matrix around the liposomes, playing a physical protective role. It can also ensure that ingredients such as heparin sodium encapsulated inside the liposomes do not leak or become inactivated, thereby ensuring the long-term stability of the liposomes in the cosmetic system. Vitamin E, as an antioxidant, can prevent the oxidation of the liposome membrane and maintain the stability of the liposome structure, thereby ensuring the liposome's ability to encapsulate and deliver active ingredients such as heparin sodium, while also avoiding the potential irritation to the skin caused by lipid peroxidation products, thereby improving the safety and effectiveness of cosmetics containing the liposomes.

[0029] Furthermore, to enhance the anti-inflammatory, moisturizing, and repairing effects of the gel, the present invention also modifies the polyquaternium salt with glutamic acid. Due to electrostatic interaction, the two form a relatively stable complex structure in solution. A certain amount of disodium EDTA is added to further enhance the stability of the polyquaternium salt complex. Polyquaternium-51 has film-forming properties and can form a moisturizing film on the skin surface, reducing water loss. It also absorbs water molecules through electrostatic interaction, enhancing the skin's hydration. Glutamic acid can regulate the skin's pH, promote hydration of the stratum corneum, and improve dryness and sensitivity. Disodium EDTA chelates metal ions, preventing oxidation and deterioration of the formula, and indirectly protecting the skin from free radical damage. The prepared polyquaternium salt complex combines these three specific properties and also has film-forming properties, which may delay the release of active ingredients and prolong the duration of action. Furthermore, its cationic properties may interact with the negative charge of the skin to promote transdermal absorption.

[0030] The applicant unexpectedly discovered that the combined application of heparin sodium liposomes and polyquaternium complexes in a gel can produce a synergistic anticoagulant and anti-inflammatory effect. Heparin sodium liposomes utilize nanocarriers to enhance transdermal penetration, targeting heparin sodium to sites of inflammation, inhibiting the NF-κB pathway and inflammatory factors while promoting wound healing. The antibacterial properties of the polyquaternium complex can reduce secondary inflammation caused by bacteria, complementing the anti-inflammatory mechanism of heparin sodium. Its film-forming properties can also reduce the intrusion of external irritants, reducing the causes of inflammation. Furthermore, glutamate regulates pH, providing a more stable environment for heparin sodium. The cationic properties of the polyquaternium may interact with the surface charge of the liposomes, enhancing their adsorption and penetration on the skin surface and improving the bioavailability of heparin sodium. The sustained-release properties of the polyquaternium, combined with the long-lasting delivery of the liposomes, extend the duration of drug action.

[0031] Compared with the prior art, the present invention has the following beneficial effects:

[0032] 1. The present invention discloses an anti-inflammatory and repairing heparin sodium liposome gel, which adopts natural raw materials such as soy lecithin and phytosterols, combines carboxymethyl chitosan and polyethylene glycol to optimize the membrane structure, significantly improving the transdermal efficiency and anti-inflammatory effect of heparin sodium; and adding a variety of moisturizers (propylene glycol, glycerin, betaine, etc.) to repair the skin barrier, and natural protective agents (sodium hyaluronate, trehalose) to enhance stability and moisturizing power.

[0033] 2. The present invention uses glutamic acid to modify the polyquaternium salt. Due to electrostatic interaction, the two form a relatively stable complex structure in the solution, and a certain amount of disodium EDTA is added to further improve the stability of the polyquaternium salt complex.

[0034] 3. The present invention applies heparin sodium liposomes and polyquaternary ammonium salt complexes together in the gel, which has a synergistic effect of anticoagulation and anti-inflammatory. DETAILED DESCRIPTION

[0035] Various exemplary embodiments of the present invention are now described in detail. This detailed description should not be considered as a limitation of the present invention, but should be understood as a more detailed description of certain aspects, characteristics and embodiments of the present invention. It should be understood that the terms described in the present invention are only for describing particular embodiments and are not intended to limit the present invention. In addition, for the numerical ranges in the present invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Each smaller range between the intermediate value within any stated value or stated range and any other stated value or intermediate value within the range is also included in the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded within the scope.

[0036] Unless otherwise indicated, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein may be used in the practice or testing of the present invention. Various modifications and variations may be made to the specific embodiments of the present invention description without departing from the scope or spirit of the present invention, as will be apparent to those skilled in the art. Other embodiments obtained from the present invention description will be apparent to those skilled in the art. This application description and examples are exemplary only.

[0037] The heparin sodium used in the present invention is low molecular weight heparin sodium (4500Da); the molecular weight of the sodium hyaluronate used is 3000-10000Da; the molecular weight of the carboxymethyl chitosan (medical grade) used is 9000Da, the carboxylation degree is ≥80%, and the purity is ≥98%.

[0038] Preparation Example 1

[0039] The preparation method of heparin sodium liposomes comprises the following preparation steps:

[0040] (1) Disperse 5 g of soybean lecithin in 100 mL of deionized water and stir in a water bath at 40°C for 30 min to obtain liquid 1; dissolve 1.5 g of phytosterol in 25 mL of anhydrous ethanol and ultrasonicate at 200 W for 15 min to obtain liquid 2; disperse 0.75 g of carboxymethyl chitosan and 1 g of polyethylene glycol 2000 in 100 mL of deionized water and stir in a water bath at 50°C and 200 rpm until clear to obtain liquid 3; add liquid 1, liquid 2, and liquid 3 into a container in sequence and homogenize at a homogenization pressure of 20 MPa and 12,000 rpm for 10 min to form an oil-in-water microemulsion;

[0041] (2) 5 g of heparin sodium was added to the oil-in-water microemulsion of step (1), and homogenization was continued for 15 min under the same parameters. After ice bath sonication for 15 min, 12 g of natural protective agent was added to the mixture, and the mixture was stirred evenly. The pH was adjusted to 6, and the mixture was filtered through a 0.22 μm sterilizing filter and freeze-dried to obtain heparin sodium liposomes.

[0042] The natural protective agents used include trehalose, sodium hyaluronate and vitamin E in a mass ratio of 60:4:1.

[0043] Preparation Example 2

[0044] The preparation method of heparin sodium liposomes comprises the following preparation steps:

[0045] (1) Disperse 4 g of soybean lecithin in 100 mL of deionized water and stir in a water bath at 40°C for 30 min to obtain liquid 1; dissolve 1 g of phytosterol in 25 mL of anhydrous ethanol and ultrasonicate at 200 W for 15 min to obtain liquid 2; disperse 0.5 g of carboxymethyl chitosan and 1 g of polyethylene glycol 2000 in 100 mL of deionized water and stir in a water bath at 50°C and 200 rpm until clear to obtain liquid 3; add liquid 1, liquid 2, and liquid 3 into a container in sequence and homogenize at a homogenization pressure of 20 MPa and 10,000 rpm for 15 min to form an oil-in-water microemulsion;

[0046] (2) 2.5 g of heparin sodium was added to the oil-in-water microemulsion of step (1), and homogenization was continued for 15 min under the same parameters. After ice bath sonication for 15 min, 2.5 g of natural protective agent was added to the mixture, and the mixture was stirred evenly. The pH was adjusted to 5.5, and the mixture was filtered through a 0.22 μm sterilizing filter and freeze-dried to obtain heparin sodium liposomes.

[0047] The natural protective agents used include trehalose, sodium hyaluronate and vitamin E in a mass ratio of 55:5:1.

[0048] Preparation Example 3

[0049] The preparation method of heparin sodium liposomes comprises the following preparation steps:

[0050] (1) Disperse 6 g of soybean lecithin in 100 mL of deionized water and stir in a water bath at 40°C for 30 min to obtain liquid 1; dissolve 2 g of phytosterol in 25 mL of anhydrous ethanol and ultrasonicate at 200 W for 15 min to obtain liquid 2; disperse 1 g of carboxymethyl chitosan and 1 g of polyethylene glycol 2000 in 100 mL of deionized water and stir in a water bath at 50°C and 200 rpm until clear to obtain liquid 3; add liquid 1, liquid 2, and liquid 3 into a container in sequence and homogenize at a homogenization pressure of 20 MPa and 15,000 rpm for 5 min to form an oil-in-water microemulsion;

[0051] (2) 6 g of heparin sodium was added to the oil-in-water microemulsion of step (1), and homogenization was continued for 15 min under the same parameters. After ice bath sonication for 15 min, 12 g of natural protective agent was added to the mixture, and the mixture was stirred evenly. The pH was adjusted to 6.5, and the mixture was filtered through a 0.45 μm sterilizing filter and freeze-dried to obtain heparin sodium liposomes.

[0052] The natural protective agents used include trehalose, sodium hyaluronate and vitamin E in a mass ratio of 65:6:1.

[0053] Preparation Example 4

[0054] The preparation method of the polyquaternium salt complex is as follows:

[0055] S1: 10 g of polyquaternium-51 was added to 100 mL of deionized water, stirred until dissolved, and the pH was adjusted to 6.5 with 0.1 M NaOH aqueous solution to obtain solution 1;

[0056] S2: 5 g of glutamic acid was added to 100 mL of deionized water, stirred until dissolved, and the pH was adjusted to 8.5 with 0.1 M NaOH aqueous solution to obtain solution 2;

[0057] S3: Solution 2 was added dropwise to solution 1, and its pH value was monitored at 6.5-7.5 during the addition process. The mixture was stirred at 300 rpm for 1.5 h, and then polyquaternium-51 and 0.1 wt% of the total mass of glutamic acid disodium EDTA were added thereto. The mixture was stirred for 0.5 h and freeze-dried to obtain a polyquaternium complex.

[0058] Preparation Example 5

[0059] The preparation method of the polyquaternium salt complex is substantially the same as that of Preparation Example 4, except that 3 g of glutamic acid is used.

[0060] Preparation Example 6

[0061] The preparation method of the polyquaternium salt complex is substantially the same as that of Preparation Example 4, except that disodium EDTA is not added.

[0062] Preparation Example 7

[0063] The preparation method of the polyquaternium salt complex is as follows:

[0064] S1: 10 g of polyquaternium-51 was added to 100 mL of deionized water, stirred until dissolved, and the pH was adjusted to 6.5 with 0.1 M NaOH aqueous solution to obtain solution 1;

[0065] S3: Solution 1 was stirred at 300 rpm for 1.5 h, and 0.1 wt% of disodium EDTA of polyquaternium-51 was added thereto, and the mixture was stirred for 0.5 h, and freeze-dried to obtain a polyquaternium complex.

[0066] Preparation Example 8

[0067] The preparation method of heparin sodium liposomes is roughly the same as that of Preparation Example 1, except that no natural protective agent is added.

[0068] Example 1

[0069] A method for preparing an anti-inflammatory and repairing heparin sodium liposome gel comprises the following steps:

[0070] (1) Step 1: Take 0.1% phenoxyethanol, calculated by mass percentage, and add it to 4.5% propylene glycol at 50° C., stirring to dissolve; then add 0.3% carbomer 940 and half the amount of water to allow the carbomer 940 to swell and disperse, to obtain solution 1, which is kept warm for later use;

[0071] (2) Step 2: According to the mass percentage, take the remaining 50°C water, add 1.5% betaine, and stir at 50°C until dissolved; then add 1.0% heparin sodium liposomes at 40°C and stir; add 5.5% glycerol and 0.3% 1,3-butanediol, stir and dissolve to obtain solution 2, and keep warm for later use;

[0072] (3) Step 3: Add solution 2 to solution 1 at 30°C according to mass percentage and stir evenly; add 0.2% triethanolamine to adjust the pH to 6.5-7.5; stir for 60 minutes; cool to 25°C under stirring, add 0.1% mint essence, stir, and fill to obtain heparin sodium liposome gel.

[0073] The heparin sodium liposomes used were obtained from Preparation Example 1.

[0074] Example 2

[0075] A method for preparing an anti-inflammatory and repairing heparin sodium liposome gel comprises the following steps:

[0076] (1) Step 1: Take 0.2% potassium sorbate by mass percentage, add it to 5.0% propylene glycol at 60°C, and stir to dissolve; then add 0.7% carbomer 940 and half the amount of water to swell and disperse the carbomer 940 to obtain solution 1, and keep it warm for later use;

[0077] (2) Step 2: Take the remaining 60°C water, add 2.0% betaine, and stir at 60°C until dissolved; add 3.0% heparin sodium liposomes at 40°C and stir; add 6.5% glycerol and 0.6% 1,3-butanediol, stir and dissolve to obtain solution 2, and keep warm for later use;

[0078] (3) Step 3: Add solution 2 to solution 1 at 45°C according to mass percentage and stir evenly; add 0.5% triethanolamine to adjust the pH to 6.5-7.5; stir for 60 minutes; cool to 30°C under stirring, add 0.2% mint essence, stir, and fill to obtain heparin sodium liposome gel.

[0079] The heparin sodium liposomes used were obtained from Preparation Example 2.

[0080] Example 3

[0081] A method for preparing an anti-inflammatory and repairing heparin sodium liposome gel comprises the following steps:

[0082] (1) Step 1: Take 0.15% p-hydroxyacetophenone by mass percentage, add it to 4.75% propylene glycol at 55°C, and stir to dissolve; then add 0.5% carbomer 940 and half the amount of water to make the carbomer 940 swell and disperse to obtain solution 1, and keep it warm for later use;

[0083] (2) Step 2: Take the remaining 55°C water, add 1.75% betaine, and stir at 55°C until dissolved; add 2.0% heparin sodium liposomes at 40°C and stir; add 6.0% glycerol and 0.45% 1,3-butanediol, stir and dissolve to obtain solution 2, and keep warm for later use;

[0084] (3) Step 3: Add solution 2 to solution 1 at 40°C according to mass percentage and stir evenly; add 0.35% triethanolamine to adjust the pH to 6.5-7.5; stir for 60 minutes; cool to 25°C under stirring, add 0.15% mint essence, stir, and fill to obtain heparin sodium liposome gel.

[0085] The heparin sodium liposomes used were obtained from Preparation Example 3.

[0086] Example 4

[0087] A method for preparing an anti-inflammatory and repairing heparin sodium liposome gel comprises the following steps:

[0088] (1) Step 1: Take 0.15% p-hydroxyacetophenone by mass percentage, add it to 4.75% propylene glycol at 55°C, and stir to dissolve; then add 0.5% carbomer 940 and half the amount of water to make the carbomer 940 swell and disperse to obtain solution 1, and keep it warm for later use;

[0089] (2) Step 2: Take the remaining 55°C water, add 1.75% betaine, and stir at 55°C until dissolved; add 2.0% heparin sodium liposomes at 40°C and stir; add 6.0% glycerol and 0.45% 1,3-butanediol, stir and dissolve to obtain solution 2, and keep warm for later use;

[0090] (3) Step 3: Add solution 2 to solution 1 at 40°C according to mass percentage and stir evenly; add 0.35% triethanolamine to adjust the pH to 6.5-7.5; then add 1.0% polyquaternium salt complex and stir for 60 minutes; under stirring, cool to 25°C, add 0.15% mint essence, stir, and fill to obtain heparin sodium liposome gel.

[0091] The heparin sodium liposomes used were obtained from Preparation Example 3, and the polyquaternary ammonium salt complex used was obtained from Preparation Example 4.

[0092] Example 5

[0093] A method for preparing an anti-inflammatory and repairing heparin sodium liposome gel, the specific implementation method is roughly the same as that of Example 4, except that the polyquaternary ammonium salt complex used is obtained from Preparation Example 5.

[0094] Example 6

[0095] A method for preparing an anti-inflammatory and repairing heparin sodium liposome gel, the specific implementation method is roughly the same as Example 4, except that the polyquaternary ammonium salt complex used is obtained from Preparation Example 6.

[0096] Example 7

[0097] A method for preparing an anti-inflammatory and repairing heparin sodium liposome gel, the specific implementation method is roughly the same as Example 4, except that the polyquaternary ammonium salt complex used is obtained from Preparation Example 7.

[0098] Example 8

[0099] A method for preparing an anti-inflammatory and repairing heparin sodium liposome gel, the specific implementation method is roughly the same as Example 4, except that equal amounts of polyquaternium-51 and glutamic acid in a mass ratio of 2:1 are used to replace the polyquaternium complex.

[0100] Example 9

[0101] A method for preparing an anti-inflammatory and repairing heparin sodium liposome gel, the specific implementation method is roughly the same as Example 4, except that the heparin sodium liposome used is obtained from Preparation Example 8.

[0102] Comparative Example 1

[0103] A method for preparing an anti-inflammatory and repairing sodium heparin gel, the specific implementation method is roughly the same as Example 3, except that an equal mass of heparin sodium is used to replace the heparin sodium liposomes.

[0104] Performance Testing

[0105] 1. Anti-inflammatory properties

[0106] 120 standard experimental mice, weighing 20±2g, half male and half female, were randomly divided into 12 groups of 10 mice each after conventional feeding for 7 days. The hydrocortisone cream-treated group served as a positive control group, the saline-treated group served as a negative control group, the Examples 1-9 groups, and the Comparative Example 1 group were used. 0.1 mL of xylene was evenly applied to the front and back surfaces of the right ears of the mice in each experimental group. 30 minutes later, 0.1 g of each of the corresponding hydrocortisone cream, saline, heparin sodium liposome gel, and heparin sodium gel were evenly applied to the front and back surfaces of the right ears of the mice in each group. The left ears served as controls. 120 minutes after administration, the mice were sacrificed by cervical dislocation. The ears were cut off along the auricle baseline. A 7 mm diameter ear punch was used to punch the same part of the left and right ears. The ears were immediately weighed accurately. The swelling degree was calculated as the weight of the right ear punch minus the weight of the left ear punch. The ear swelling rate was calculated as (right ear weight - left ear weight) / left ear weight × 100%, and the average value was taken. The test results are shown in Table 1.

[0107] Table 1

[0108]

[0109] As shown in Table 1, the heparin sodium liposome gel prepared by embodiment 1-3 has good anti-inflammatory effect, and embodiment 4 further improves its anti-inflammatory effect owing to having added the polyquaternium complex.Compared to embodiment 4, the preparation parameter of polyquaternium complex used in embodiment 5-7 changes, and its performance is affected to some extent, so that the anti-inflammatory effect has reduction to varying degrees; Polyquaternium-51 and glutamic acid of corresponding proportion were added separately in embodiment 8, and the two also have certain anti-inflammatory effect, but the effect is less than the effect of the polyquaternium complex, and the anti-inflammatory effect decreases to some extent; In embodiment 9, natural protective agent is not added in heparin sodium liposome used, stability and the anti-inflammatory effect of liposome are affected.Compared to embodiment 3, use heparin sodium to replace heparin sodium liposome in comparative example 1, may also affect anti-inflammatory effect because heparin sodium permeability is poor than liposome.

[0110] 2. The following tests were performed on the heparin sodium liposome gels of Examples 3, 4, and Comparative Example 1:

[0111] 2.1 Stability test: Take each prepared heparin sodium liposome gel\heparin sodium gel, place them in sealed containers, store them at an ambient temperature of 37±2°C, and perform accelerated aging test. Take samples on the 60th day to test the pH and observe the appearance of the product.

[0112] 2.2 Cytotoxicity test: performed with reference to patent CN 118105321 A.

[0113] 2.3 Repairability test: According to T / OGCML450-2022 "Determination of the repair efficacy of cosmetics - zebrafish embryo method", the repair efficacy of each heparin sodium liposome gel\heparin sodium gel was tested (fish embryo method).

[0114] The specific test results are shown in Table 2.

[0115] Table 2

[0116]

[0117] As shown in Table 2, the heparin sodium liposome gels prepared in Examples 3 and 4 have good stability, low cytotoxicity, and good repair effect, and are superior to the gel using ordinary heparin sodium in Comparative Example 1.

[0118] The above description is merely a preferred embodiment of the present invention and does not constitute any form of limitation to the present invention. Although the present invention has been disclosed as a preferred embodiment, it is not intended to limit the present invention. Any technician familiar with the present profession can make some changes or modifications to equivalent embodiments of equivalent changes using the technical contents disclosed above without departing from the scope of the technical solution of the present invention. However, any simple modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention are still within the scope of the technical solution of the present invention.

Claims

1. An anti-inflammatory and restorative heparin sodium liposome gel, characterized in that: Calculated by mass percentage, it includes the following components: Heparin sodium liposome 1.0-3.0%, moisturizer 11.8-14.1%, triethanolamine 0.2-0.5%, thickener 0.3-0.7%, preservative 0.1-0.2%, flavor 0.1-0.2%, and the balance is water.

2. The heparin sodium liposome gel according to claim 1, characterized in that The moisturizing agent comprises 4.5-5.0% of propylene glycol, 5.5-6.5% of glycerin, 0.3-0.6% of 1,3-butylene glycol and 1.5-2.0% of betaine.

3. The heparin sodium liposome gel according to claim 1, characterized in that The preparation method of the heparin sodium liposome is: (1) Dispersing soybean lecithin in deionized water and stirring in a water bath to obtain liquid 1; dissolving phytosterol in ethanol and ultrasonicating to obtain liquid 2; dispersing carboxymethyl chitosan and polyethylene glycol in deionized water and stirring in a water bath until clear to obtain liquid 3; adding liquid 1, liquid 2, and liquid 3 into a container in sequence and homogenizing to form an oil-in-water microemulsion; (2) adding heparin sodium to the oil-in-water microemulsion of step (1), continuing homogenization, ultrasonicating in an ice bath, and then adding a natural protective agent to the mixture, stirring evenly, adjusting the pH, and sterilizing and filtering to obtain heparin sodium liposomes.

4. The method for preparing the high permeability heparin sodium liposome according to claim 3, characterized in that: The mass ratio of soybean lecithin, phytosterol, carboxymethyl chitosan and polyethylene glycol in the oil-in-water microemulsion in step (1) is (4-6):(1-2):(0.5-1):

1.

5. The method for preparing the high permeability heparin sodium liposome according to claim 3, characterized in that: The amount of heparin sodium added in step (2) is 1-2.5 wt% of the oil-in-water microemulsion.

6. The method for preparing the high permeability heparin sodium liposome according to claim 3, characterized in that: The natural protective agent in step (2) includes sodium hyaluronate, trehalose and vitamin E; the amount of the natural protective agent is 1-5wt% of the mixture.

7. The heparin sodium liposome gel according to claim 1, characterized in that Calculated by mass percentage, the component further comprises 0.5-2.0% of a polyquaternary ammonium salt complex.

8. The heparin sodium liposome gel according to claim 7, characterized in that The preparation method of the polyquaternium salt complex is: S1: Add polyquaternium-51 to deionized water, stir until dissolved, and adjust the pH to 6.5-7.0 to obtain solution 1; S2: Add glutamic acid to deionized water, stir until dissolved, and adjust the pH to 8.0-9.0 to obtain solution 2; S3: Solution 2 is added dropwise to solution 1, stirred for 1-2 hours, and then disodium EDTA is added thereto, stirred, and dried to obtain a polyquaternary ammonium salt complex.

9. The heparin sodium liposome gel according to claim 8, characterized in that The mass ratio of the polyquaternium-51 to glutamic acid is 1:(0.5-2).

10. A method for preparing the heparin sodium liposome gel according to any one of claims 1 to 9, characterized in that: The following steps are involved: (1) Step 1: Take a preservative, add it to propylene glycol at 50-60°C, and stir to dissolve; then add a thickener and part of the water to make the thickener swell and disperse to obtain solution 1, and keep it warm for later use; (2) Step 2: Take the remaining water, add betaine, and stir at 50-60°C until dissolved; then add heparin sodium liposomes and stir; add glycerol and 1,3-butanediol and stir to dissolve to obtain solution 2, which is kept warm for later use; (3) Step 3: Add solution 2 to solution 1 at 30-45°C and stir evenly; add triethanolamine to adjust the pH to 6.5-7.5; stir; under stirring, cool to 25-30°C, add flavoring, stir, and fill to obtain heparin sodium liposome gel.

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