Forsythin lipidosome, forsythin gel and preparation method of forsythin lipidosome and forsythin gel

Abstract

The invention discloses forsythin lipidosome, forsythin gel and a preparation method of the forsythin lipidosome and the forsythin gel, and belongs to the technical field of medical materials. The forsythin liposome with high skin transmittance and high bioavailability is prepared by taking forsythin, cholesterol, lecithin and penetration enhancer as raw materials. The penetration enhancer not only can increase the skin permeability of the medicine and improve the skin transmittance, but also can regulate and control the forsythin liposome to carry positive charges, and the forsythin liposome with the positive charges is better combined with the skin with negative charges, so that the skin permeability of the liposome is promoted; the phillyrin lipidosome with positive electricity has strong electrostatic interaction with bacteria, cell membranes of the bacteria can be destroyed, substances in bacterial cells are leaked, bacteria apoptosis is caused, and a good skin antibacterial effect is further achieved.

Description

Technical Field

[0001] The invention relates to the technical field of medical materials, and in particular to forsythiaside liposomes and gels and methods for preparing the forsythiaside liposomes and gels. Background Art

[0002] Forsythia suspensa is an extract of the dried fruit of the plant Forsythia suspensa of the Oleaceae family. Forsythia suspensa can be used as medicine, and has the effects of clearing away heat, detoxifying, dispersing knots and discharging pus, etc. It is mainly used to treat febrile diseases, sores, scrofula, erysipelas, maculopapular rash, influenza, the initial stage of febrile diseases, febrile diseases entering the camp, high fever, thirst, coma and spots, and heat stranguria and urinary retention; Forsythia suspensa can be decocted in water or added to prescriptions. It has a wide range of uses in human medicine, veterinary medicine, and agriculture.

[0003] Transdermal drug delivery system has become the most important drug delivery method besides oral and injection due to its unique advantages. The skin is the natural barrier of the human body and hinders drug absorption. Therefore, increasing the transdermal permeability of drugs by promoting transdermal absorption is a research hotspot of new topical preparation technology of traditional Chinese medicine. As the main active ingredient of Forsythia suspensa, Forsythia suspensa has anti-inflammatory effects and can reduce tissue inflammatory response. However, Forsythia suspensa has poor water solubility, is not resistant to high temperatures, and has poor acid-base stability. There is a problem of low compatibility with water-soluble matrices when preparing it as a transdermal drug delivery preparation. The use of nanoliposome technology for transdermal drug delivery can not only effectively solve this problem, but also, because the liposome composition is similar to the skin structure, it is not easily rejected by the body, and it can change the permeability of the skin barrier, increase the content of drugs on the skin, make it easier for drugs to penetrate into the skin and tissues, and fully exert the therapeutic effect on local tissues. However, the existing Forsythia suspensa nanoliposomes have poor skin permeability, and the delivery efficiency and bioavailability of Forsythia suspensa through the skin are low, and a better therapeutic effect cannot be achieved. Summary of the invention

[0004] The invention provides forsythiaside liposomes and gel and methods for preparing forsythiaside liposomes and gel, which effectively solve the technical problems that the existing nanoliposomes have poor skin permeability, low delivery efficiency and bioavailability of forsythiaside through the skin, and cannot achieve better therapeutic effects. At the same time, a forsythiaside liposome gel with uniform and fine texture, suitable pH value, easy spreading, good centrifugal stability, heat stability and cold stability, easy application and convenient use is provided.

[0005] The first object of the present invention is to provide a forsythiaside liposome, which is prepared from the following raw materials in parts by weight: 1.0-5.0 parts of forsythiaside, 4-15 parts of lecithin, 1.0-5.0 parts of cholesterol, and 0.5-5.0 parts of a penetration enhancer.

[0006] As a preferred embodiment, the penetration enhancer is stearylamine and / or vitamin E.

[0007] The second object of the present invention is to provide a method for preparing forsythiaside liposomes, comprising the following steps:

[0008] Weigh 1.0-5.0 parts of forsythiaside, 4-15 parts of lecithin, 1.0-5.0 parts of cholesterol, and 0.5-5.0 parts of a penetration enhancer.

[0009] Add ethanol to the above raw materials in different mass fractions, mix and dissolve to obtain an organic phase, add the organic phase into water under stirring, hydrate at 30-60° C., remove ethanol by vacuum distillation to obtain forsythiaside liposomes.

[0010] As a preferred embodiment, the hydration treatment time is 0.5 to 3 hours.

[0011] As a preferred embodiment, during mixed dissolution, ultrasonic dissolution is performed at 40-60°C, 250W, 34kHz for 0.5h-2h; after reduced pressure distillation, ultrasonic treatment is performed at 30-60°C, 250W, 34kHz for 0.5-3h.

[0012] The third object of the present invention is to provide a forsythiaside liposome gel, which is prepared by using the forsythiaside liposome.

[0013] The fourth object of the present invention is to provide a method for preparing forsythiaside liposome gel, comprising the following steps:

[0014] Add water to the gel matrix, disperse it evenly and fully swell it, add a moisturizer, mix it evenly, and then add triethanolamine or sodium hydroxide to adjust the pH value to 6.0-8.0 to obtain a blank gel.

[0015] The blank gel and the forsythiaside liposomes are mixed to obtain an antibacterial gel.

[0016] As a preferred embodiment, the mass ratio of the blank gel to the forsythiaside liposomes is 1:0.5-2.

[0017] As a preferred embodiment, the preparation method according to claim 7 is characterized in that, in the blank gel, the mass fraction of the gel matrix is ​​0.5% to 3.0%, the mass fraction of the moisturizer is 5% to 15%, and the mass fraction of triethanolamine or sodium hydroxide is 0.5% to 1.5%.

[0018] As a preferred embodiment, the gel matrix is ​​carbomer-940, hydroxypropyl methylcellulose or sodium carboxymethyl cellulose; the moisturizing agent is glycerol, polyethylene glycol-2000 or polyethylene glycol-6000.

[0019] Compared with the prior art, the present invention has the following beneficial effects:

[0020] (1) The present invention uses forsythia glycosides, cholesterol, lecithin, and a penetration enhancer as raw materials to prepare a forsythia glycoside liposome with high skin permeability and high bioavailability. The penetration enhancer not only increases the skin permeability of forsythia glycosides and improves the skin permeability, but also can regulate the forsythia glycoside liposomes to carry a positive charge, and the positively charged forsythia glycoside liposomes can achieve a better combination with the negatively charged skin, thereby promoting the skin permeability of the liposomes. In addition, the positively charged forsythia glycoside liposomes have a strong electrostatic interaction with bacteria, which can destroy the bacterial cell membrane, leading to the leakage of bacterial intracellular substances, thereby causing bacterial apoptosis, and further achieving a better skin antibacterial effect.

[0021] (2) The forsythiaside liposomes prepared by the present invention have a good antibacterial effect on the skin, and the antibacterial effect of the prepared forsythiaside liposomes is evaluated by the inhibition zone method. The forsythiaside liposomes prepared by the present invention have a certain improvement in the antibacterial effect on a variety of test bacteria, and the diameters of the inhibition zones are 12.46±0.12mm for Escherichia coli, 12.89±0.15mm for Staphylococcus aureus, 13.16±0.17mm for Pseudomonas aeruginosa, and 11.20±0.14mm for Bacillus subtilis; however, although the forsythiaside liposomes prepared in Comparative Example 1 also have a certain inhibitory effect on the test bacteria, the diameters of the inhibition zones are Escherichia coli (10.77±0.12mm), Staphylococcus aureus (9.87±0.16mm), Pseudomonas aeruginosa (9.89±0.15mm), and Bacillus subtilis (9.17±0.18mm).

[0022] (3) The antibacterial gel (forsythiaside liposome gel) prepared by the present invention has good stability. The antibacterial gel of the present invention was subjected to centrifugal stability test, high temperature test and low temperature test. The results showed that no stratification, turbidity, color change and the like were found, so the stability was good. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 This is the appearance diagram of the Forsythiaside liposome prepared in the present invention.

[0024] Figure 2 The particle size of the forsythiaside liposome prepared by the present invention.

[0025] Figure 3 The cumulative permeation amount of forsythiaside in different forsythiaside liposomes (n=3).

[0026] Figure 4 The in vitro cumulative release curves of forsythiaside from different forsythiaside liposome gels (n=3).

[0027] Figure 5 This is a stability experiment of the forsythiaside liposome gel prepared by the present invention; wherein 5 is application comparative example 2, 6 is application comparative example 1, and 7 is application example 1. DETAILED DESCRIPTION

[0028] In order to enable those skilled in the art to better understand the technical solution of the present invention and implement it, the present invention is further described below in conjunction with specific examples, but the examples are not intended to limit the present invention. The following test methods and detection methods, unless otherwise specified, are conventional methods; the reagents and raw materials, unless otherwise specified, are commercially available.

[0029] In view of the poor water solubility, high temperature resistance and poor acid-base stability of forsythin mentioned in the background technology of the present invention, there is a problem of low compatibility with water-soluble matrix when preparing it as a transdermal preparation. The use of nanoliposome technology for transdermal administration can not only effectively solve this problem. In addition, since the liposome components are similar to the skin structure, they are not easily rejected by the body, and can change the permeability of the skin barrier, increase the content of the drug on the skin, make the drug more easily penetrate into the skin and tissue, and fully exert the therapeutic effect on local tissues. However, the existing forsythin nanoliposomes have the problems of strong fluidity and inconvenient use. In addition, the skin permeability of nanoliposomes is poor, and the delivery efficiency and bioavailability of forsythin through the skin are low, and a better therapeutic effect cannot be achieved. Based on the above technical problems, the present invention provides forsythin liposomes, gels and methods for preparing forsythin liposomes and gels.

[0030] The technical contents of the present invention are described in detail below.

[0031] The invention firstly provides a forsythiaside liposome, which is composed of the following raw materials in parts by weight: 1.0-5.0 parts of forsythiaside, 4-15 parts of lecithin, 1.0-5.0 parts of cholesterol and 0.5-5.0 parts of a penetration enhancer.

[0032] In the above technical scheme, forsythiaside liposomes are prepared with forsythiaside, cholesterol and lecithin as base materials. The addition of a penetration enhancer can increase the skin permeability of forsythiaside and improve the skin permeability, and can also regulate the positive charge of the forsythiaside liposomes, and the positively charged forsythiaside liposomes can achieve better bonding with the negatively charged skin, thereby promoting the skin permeability of the liposomes. In addition, the positively charged forsythiaside liposomes have a strong electrostatic interaction with bacteria, which can destroy the bacterial cell membrane, leading to the leakage of bacterial intracellular substances, thereby causing bacterial apoptosis, and further achieving a better skin antibacterial effect.

[0033] The present invention also provides a method for preparing forsythiaside liposomes, comprising the following steps:

[0034] Weigh 1.0-5.0 parts of forsythiaside, 4-15 parts of lecithin, 1.0-5.0 parts of cholesterol, and 0.5-5.0 parts of a penetration enhancer.

[0035] Add ethanol to the above-mentioned raw materials by mass, mix and dissolve to obtain an organic phase, slowly add the organic phase into ultrapure water under stirring, hydrate at 30-60°C, and remove ethanol by vacuum distillation to obtain forsythiaside liposomes. Too high or too low temperature will affect the encapsulation rate of forsythiaside in the liposomes. Hydration refers to high-speed stirring at this temperature to ensure that uniform and stable liposomes can be obtained.

[0036] In order to fully dissolve all the raw materials and achieve the uniformity of the components in the forsythiaside liposomes, ultrasonic dissolution is performed at 40-60° C. Too low a temperature will affect the dissolution rate; too high a temperature will waste energy and may also damage the components.

[0037] As a preferred embodiment, the hydration treatment time is 0.5 to 3 hours. If the treatment time is too short, the particle size and distribution of the liposomes will be affected, resulting in larger particle size and uneven distribution of the system; if the treatment time is too long, the stability of the liposomes may be damaged.

[0038] As a preferred embodiment, after the reduced pressure distillation, ultrasonic treatment is performed at 30-60° C. for 0.5-3 h. Too short a treatment time will result in too large a liposome particle size and uneven distribution. Too long a treatment time may destroy the liposome and cause leakage of the drug (forsythin).

[0039] The third object of the present invention is to provide a forsythiaside liposome gel, which is prepared by using the forsythiaside liposome.

[0040] The fourth object of the present invention is to provide a method for preparing forsythiaside liposome gel, comprising the following steps:

[0041] Add water to Carbomer 940 to disperse evenly and fully swell, add glycerol, mix well, and then add triethanolamine or sodium hydroxide to adjust the pH value to 6.0-8.0 to obtain a blank gel.

[0042] The blank gel and the forsythiaside liposomes are mixed to obtain an antibacterial gel.

[0043] As a preferred embodiment, the mass ratio of the blank gel to the forsythiaside liposome is 1:1. 1:1 is the best ratio. Liposome gel can be obtained when the ratio exceeds this ratio, but its properties such as appearance, viscosity, and spreadability will be affected to a certain extent.

[0044] As a preferred embodiment, in the blank gel, the mass fraction of the gel matrix is ​​0.5% to 3.0%, the mass fraction of glycerol is 5% to 15%, and the mass fraction of triethanolamine or sodium hydroxide is 0.5% to 1.5%. In the present invention, appearance, viscosity, spreadability and centrifugal stability are used as evaluation indicators for comprehensive scoring. Gels prepared outside these ranges will have certain deficiencies in these indicators.

[0045] The technical effects of this case are described below in conjunction with specific embodiments and comparative examples.

[0046] 1. Preparation of Forsythiaside Liposomes

[0047] Comparative Example 1: No Vitamin E and Stearylamine Added

[0048] The present invention provides a method for preparing forsythiaside liposomes, comprising the following steps:

[0049] (1) Organic phase: Weigh 100 mg of forsythin, 400 mg of lecithin and 100 mg of cholesterol into a beaker, add 20 mL of anhydrous ethanol to the beaker, and dissolve by ultrasonication at 50°C.

[0050] (2) Aqueous phase: 20 mL purified water.

[0051] (3) The aqueous phase (2) was heated to 50°C, and the organic phase (1) was slowly added to the aqueous phase under stirring, and hydrated for 1 hour. The ethanol was removed by vacuum distillation. Then, the mixture was ultrasonicated at 50°C for 1 hour to prepare comparative forsythiaside liposomes.

[0052] Example 1: No stearylamine added

[0053] The preparation method of the forsythiaside liposome I of the present invention comprises the following steps:

[0054] (1) Organic phase: Weigh 100 mg of forsythin, 400 mg of lecithin, 100 mg of cholesterol and 50 mg of vitamin E into a beaker, then add 20 mL of anhydrous ethanol to the beaker and set the ultrasonic temperature to 50°C for dissolution.

[0055] (2) Aqueous phase: 20 mL purified water.

[0056] (3) The aqueous phase (2) was heated to 50°C, and the organic phase (1) was slowly added to the aqueous phase under stirring, and hydrated for 1 hour. After hydration was completed, the ethanol was removed by vacuum distillation. Then, ultrasonication was performed at 50°C for 1 hour to obtain forsythiaside liposome I.

[0057] Example 2: No Vitamin E Added

[0058] The preparation method of forsythiaside liposome II of the present invention comprises the following steps:

[0059] (1) Organic phase: Weigh 100 mg of forsythiaside, 100 mg of stearylamine, 400 mg of lecithin and 100 mg of cholesterol in 20 mL of anhydrous ethanol and set the ultrasonic temperature to 50°C for dissolution.

[0060] (2) Aqueous phase: 20 mL purified water.

[0061] (3) The aqueous phase (2) was heated to 55°C, and the organic phase (1) was slowly added to the aqueous phase under stirring, and hydrated for 1 hour. After hydration was completed, the ethanol was removed by distillation under reduced pressure. Then, ultrasonic treatment was performed at 50°C for 1 hour to obtain forsythiaside liposome II.

[0062] Example 3: Adding Vitamin E and Stearylamine Simultaneously

[0063] The preparation method of the forsythiaside liposome III of the present invention comprises the following steps:

[0064] (1) Organic phase: Weigh 100 mg of forsythiaside, 100 mg of stearylamine, 50 mg of vitamin E, 400 mg of lecithin and 100 mg of cholesterol into a beaker, add 20 mL of anhydrous ethanol to the beaker, and dissolve them under ultrasonic temperature set at 50°C.

[0065] (2) Aqueous phase: 20 mL purified water.

[0066] (3) The aqueous phase (2) was heated to 50°C, and the organic phase (1) was slowly added to the aqueous phase under stirring, and hydrated for 1 hour. After hydration was completed, the ethanol was removed by vacuum distillation. Then, the mixture was ultrasonicated at 50°C for 1 hour to obtain forsythiaside liposome III.

[0067] from Figure 1 It can be seen that the several forsythiaside liposomes prepared in the present invention are light brown, uniformly dispersed, and have no floccules or precipitation, indicating that they all have good stability and uniformity.

[0068] Table 1 Particle size and potential data of forsythiaside liposomes

[0069] Liposome name Particle size (nm) PDI Potential (mV) Comparative Example 1 280.47 0.243 -23.6419 Example 1 283.92 0.193 -13.6948 Example 2 332.94 0.206 16.1488 Example 3 295.92 0.201 22.2384

[0070] The particle size and potential of these liposomes were measured using a Be Nano 180Zeta nanoparticle size and Zeta potential analyzer (Dandong Better Instrument Co., Ltd.), and the results are shown in Table 1. The particle size distribution of each liposome is within a reasonable range, indicating that the liposome structure is complete and has good dispersibility. As can be seen from Table 1, Comparative Example 1 and Example 1 are negatively charged, while Examples 2 and 3 have positive potentials due to the addition of stearylamine to their liposome formulas, which is beneficial for combining with skin with negative surface charge and promoting skin permeability; it is also beneficial for combining with bacteria with negative surface charge and enhancing the antibacterial effect of liposomes.

[0071] 2. Preparation of Forsythiaside Liposome Gel

[0072] Application Comparative Example 1: No Vitamin E and Stearylamine

[0073] The preparation method of forsythiaside liposome gel comprises the following steps:

[0074] (1) Weigh 0.75% by weight of gel matrix Carbomer 940, 10% by weight of glycerol, 1% by weight of triethanolamine, and the remainder being purified water.

[0075] (2) The weighed Carbomer 940 is uniformly dispersed in purified water to fully swell; then the above amount of glycerol is added and stirred evenly; then the above amount of triethanolamine is added to adjust the pH value to 7 to obtain a blank gel.

[0076] (3) The comparative forsythiaside liposomes in comparative example 1 and the blank gel in (2) were mixed (1:1) and stirred evenly to obtain a comparative forsythiaside liposome gel.

[0077] Application Comparative Example 2: No Forsythiaside Liposomes were used, only Forsythiaside was used

[0078] The preparation method of forsythiaside suspension gel comprises the following steps:

[0079] (1) Weigh 0.75% by weight of gel matrix Carbomer 940, 10% by weight of glycerol, 1% by weight of triethanolamine, and the remainder being purified water.

[0080] (2) The weighed Carbomer 940 is uniformly dispersed in purified water to fully swell; then the above amount of glycerol is added and stirred evenly; then the above amount of triethanolamine is added to adjust the pH value to 7 to obtain a blank gel.

[0081] (3) Preparation of forsythiaside suspension: Weigh 100 mg of forsythiaside into a beaker, add 20 mL of purified water into the beaker, and stir until the suspension is evenly dispersed.

[0082] (4) The forsythiaside suspension in (3) and the blank gel in (2) are mixed (1:1) and stirred evenly to obtain a forsythiaside suspension gel.

[0083] Application Example 1

[0084] The preparation method of forsythiaside liposome III gel comprises the following steps:

[0085] (1) Weigh 0.75% by weight of gel matrix Carbomer 940, 10% by weight of glycerol, 1% by weight of triethanolamine, and the remainder being purified water.

[0086] (2) The weighed Carbomer 940 is uniformly dispersed in purified water to fully swell; then the above amount of glycerol is added and stirred evenly; then the above amount of triethanolamine is added to adjust the pH value to 7 to obtain a blank gel.

[0087] (3) The Forsythiaside Liposome III prepared in Example 3 was mixed with the blank gel prepared in (2) at a ratio of 1:1 and stirred evenly to obtain the Forsythiaside Liposome III gel.

[0088] 3. The drug in vitro transdermal experiment was conducted on the forsythiaside liposomes prepared in the above Examples 1 to 3 and Comparative Example 1. The specific process is as follows:

[0089] Experimental instrument: TP-6 ​​intelligent transdermal experimental instrument, Tianjin Shengda Sanhe Optical Instrument Co., Ltd.

[0090] Experimental ex vivo skin: SPF grade SD mice (male), back skin with hair removed and subcutaneous connective tissue removed, each implementation case was measured in parallel 3 times.

[0091] Experimental method: Fix the skin on the Franz diffusion cell with the stratum corneum facing up and fix it with a spring clip. Fill the diffusion cell with water to check for leaks and ensure that there is no leakage. Use a syringe to add the receiving solution (phosphate buffer with pH = 7) into the receiving cell and put in a small magnet to ensure that there are no bubbles at the contact interface between the skin and the receiving solution. Add 1 mL of each of the four forsythiaside liposomes to the supply cell to ensure that the drug is in contact with the skin. Place the Franz diffusion cell on a thermostatic stirrer, keep the water bath at a constant temperature of 37°C, stir at a constant speed of 300 r / min, and determine that the contact area of ​​the skin is 1.54 cm 2 Subsequently, 2 mL of the receiving solution was accurately taken out from the receiving pool at predetermined time intervals (2, 4, 6, 8, 12, and 24 hours), and 2 mL of the receiving solution was immediately added to keep the volume of the receiving pool constant. In order to quantify the penetration of forsythin, the content of forsythin was measured by UV-visible spectrophotometer at a wavelength of 277 nm and calculated using the following formula:

[0092]

[0093] In this formula, Q n is the cumulative permeation per unit area (μg / cm 2 ), Vi represents the sampling volume at the ith time point (mL), Ci represents the drug concentration measured at the ith time point (μg / mL), and A represents the skin contact area (cm 2 ).

[0094] Depend on Figure 3 It can be seen that compared with the forsythiaside liposomes prepared in Comparative Example 1, the forsythiaside liposomes prepared by adding vitamin E (Example 1) or stearylamine (Example 2) on the basis of the forsythiaside liposomes prepared by adding vitamin E (Example 1) or stearylamine (Example 2) have significantly improved skin permeation. Among them, the forsythiaside liposomes prepared by adding vitamin E and stearylamine at the same time (Example 3) have the highest cumulative skin permeation. This shows that both vitamin E and stearylamine have good permeation-promoting effects.

[0095] Fourth, antibacterial experiments were carried out on the forsythiaside liposomes prepared in Examples 1 to 3 of the present invention and Comparative Example 1. The specific implementation scheme is as follows:

[0096] The present invention adopts agar plate method to carry out antibacterial experiment. First, prepare agar medium according to standard microbiological experimental method, and sterilize under aseptic conditions. Then, pour the sterilized agar medium into a sterile culture dish, wait for it to cool and solidify to form a plate. Then take a small amount from the preserved bacteria, inoculate it into a liquid culture medium containing corresponding nutrients, and activate it. Cultivate in a constant temperature incubator to the logarithmic growth phase to ensure the activity and quantity of the bacteria. Dilute the activated bacterial solution with sterile physiological saline to an appropriate concentration to prepare a bacterial suspension. Use a sterile pipette to draw a certain amount of bacterial suspension, evenly add it dropwise to the cooled and solidified agar plate, and evenly spread the bacterial suspension on the surface of the agar plate with a sterile coating rod.

[0097] Five areas were set on the agar plate, corresponding to the four forsythia glycoside liposomes and the blank control group. The corresponding liposome solution was drawn with a pipette and dropped onto a 6 mm sterile filter paper sheet at the center of each area. Finally, the inoculated agar plate was placed in a constant temperature incubator, and the appropriate temperature and humidity were set for incubation for 24 hours. Then the agar plate was taken out, and the antibacterial effect of each area was observed and recorded, and the size of the antibacterial circle was recorded. By comparing the effects of different liposome formulas on the antibacterial effect, the antibacterial effects of the four forsythia glycoside liposomes on the four bacteria can be evaluated.

[0098] Table 2 Antibacterial activity of forsythiaside liposomes against four tested bacteria

[0099]

[0100] As can be seen from Table 2, the forsythiaside liposomes prepared in Comparative Example 1 have a certain inhibitory effect on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus subtilis. When vitamin E (Example 1) is added to the liposome formula, the inhibitory effect on these four test bacteria is improved to a certain extent. Since the surfaces of these several test bacteria are negatively charged, stearylamine (Example 2 and Example 3) is added to the liposome formula, and the two prepared forsythiaside liposomes are positively charged, which promotes the combination of the forsythiaside liposomes and the test bacteria, so the antibacterial effect is further improved.

[0101] V. A stability experiment was conducted on the forsythiaside liposome gel prepared in Comparative Examples 1 to 2 and Example 1 of the present invention. The specific implementation scheme is as follows:

[0102] Weigh 1 g of each of the forsythiaside liposome gels prepared in Comparative Examples 1 to 2 and Application Example 1, put them into a dialysis bag (MW8000-14000), tie the two ends of the dialysis bag with fine wires, remove the bubbles in the bag, and then put it into 100 mL of PBS (pH=7.4) buffer solution, the upper edge of the dialysis bag should be immersed in the liquid surface for about 1 cm, keep the temperature in a water bath to 37° C., stir at a constant speed of 100 r / min, and sample 5 mL at 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, and 72 h (and add 5 mL of isothermal PBS).

[0103] The content of forsythiaside in the dialysis medium was determined by UV-visible spectrophotometry at a wavelength of 277 nm, and the cumulative release rate of the drug Qr (%) was calculated as follows:

[0104]

[0105] In the formula, Qr is the cumulative release rate at the rth time point, Cr represents the drug concentration measured at the rth time point (mg / mL), Vr represents the sampling volume at the rth time point (mL), and W is the content of the gel drug taken (mg / g).

[0106] Depend on Figure 4 It can be seen that the 0-12h forsythiaside suspension gel (application comparative example 2) releases faster, and the cumulative drug release rate has exceeded 90% at 18h, and the drug release tends to be flat after 18h. Compared with the forsythiaside suspension gel, under the same conditions, the drug release rates of the two forsythiaside liposome gels (application comparative example 1 and application example 1) are relatively low, and as the release time is extended, the drug release rates of the two are improved to a certain extent. After the cumulative release of the two forsythiaside liposome gels for 48h, the drug release tends to be stable, and the cumulative release rate is about 80%. The results show that compared with the forsythiaside suspension gel, the two forsythiaside liposome gels have a certain sustained release effect.

[0107] VI. A stability experiment was conducted on the forsythiaside gel prepared by using comparative examples 1 to 2 and example 1 of the present invention. The specific implementation scheme is as follows:

[0108] Centrifugation experiment

[0109] Take the forsythiaside gel prepared in the present invention, weigh 2 g each, add it into a centrifuge tube, centrifuge it at 6000 r / min for 15 min, and observe whether the forsythiaside liposome gel has stratification and whether the color changes.

[0110] High temperature experiment

[0111] Take the forsythiaside gel prepared in the present invention, weigh 2 g each, place it in a 60° C. oven for 10 days, and take samples to observe whether stratification, turbidity, and color change occur.

[0112] Low temperature experiment

[0113] Take the forsythiaside gel prepared in the present invention, weigh 2 g each, put it in a -24°C refrigerator, take it out after 10 days, and observe whether the forsythiaside liposome gel has stratification and whether the color changes.

[0114] The above stability test results of the Forsythia suspensa gel prepared by using Comparative Examples 1 to 2 and Example 1 of the present invention are shown in Table 3.

[0115] Table 3 Stability test results of the forsythiaside gel of comparative examples 1 to 2 and example 1 of the present invention

[0116]

[0117] The above results show that the three gels prepared by the present invention (comparative examples 1 to 2 and example 1) did not undergo stratification, phase change or color change whether in a low temperature state, a high temperature state or when centrifuged at a higher speed, indicating that the three gels prepared by the present invention are relatively stable in daily life.

[0118] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. A forsythiaside liposome, characterized in that: The invention is prepared from the following raw materials in parts by weight: 1.0 to 5.0 parts of forsythiaside, 4 to 15 parts of lecithin, 1.0 to 5.0 parts of cholesterol and 0.5 to 5.0 parts of a penetration enhancer.

2. The forsythiaside liposome according to claim 1, characterized in that The penetration enhancer is stearylamine and / or vitamin E.

3. A method for preparing the forsythiaside liposome according to claim 1, characterized in that: The following steps are involved: Weigh 1.0-5.0 parts of forsythin, 4-15 parts of lecithin, 1.0-5.0 parts of cholesterol, and 0.5-5.0 parts of a penetration enhancer; Add ethanol to the above raw materials by mass, mix and dissolve to obtain an organic phase, add the organic phase into water under stirring, hydrate at 30-60° C., remove ethanol by vacuum distillation, and obtain forsythiaside liposomes by ultrasound.

4. The preparation method according to claim 3, characterized in that: The time of the hydration treatment is 0.5 to 3 hours.

5. The preparation method according to claim 3, characterized in that: When mixed and dissolved, ultrasonically dissolve at 40-60°C, 250W, 34kHz for 0.5h-2h; after reduced pressure distillation, ultrasonically treat at 30-60°C, 250W, 34kHz for 0.5-3h.

6. A forsythiaside liposome gel prepared by using the forsythiaside liposome according to claim 1 or 2.

7. A method for preparing the forsythiaside liposome gel according to claim 6, characterized in that: The following steps are involved: Add water to the gel matrix, disperse it evenly and fully swell it, add a moisturizer, mix it evenly, and adjust the pH value to 6.0-8.0 to obtain a blank gel; The blank gel and the forsythiaside liposomes are mixed to obtain an antibacterial gel.

8. The preparation method according to claim 7, characterized in that: The mass ratio of the blank gel to the forsythiaside liposome is 1:0.5-2.

9. The preparation method according to claim 7, characterized in that: In the blank gel, the mass fraction of the gel matrix is ​​0.5% to 3.0%, and the mass fraction of the moisturizer is 5% to 15%.

10. The preparation method according to claim 7, characterized in that: The gel matrix is ​​carbomer-940, hydroxypropyl methylcellulose or sodium carboxymethyl cellulose; the moisturizing agent is glycerin, polyethylene glycol-2000 or polyethylene glycol-6000.

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