Bee sponge spicule gel as well as preparation method and application thereof

Abstract

The invention discloses bee sponge spicule gel and a preparation method and application thereof, the bee sponge spicule gel is prepared from the following raw material components in percentage by mass: 1-4 wt% of bee sponge spicule, 5-6 wt% of propylene glycol, 0.5-0.8 wt% of carbomer, 0.13-0.14 wt% of sodium hydroxide, 0.2 wt% of ethylparaben and the balance of deionized water, and the dosage of the bee sponge spicule gel is 10-20 mg / 1.5-2.0 cm < 2 > skin. By means of pressing and smearing, the bee sponge bone needle pierces into the cuticle of the skin at a random angle, and a large number of nanoscale micro-channels are formed in the surface of the skin. The microchannels can open a skin barrier and promote transdermal absorption of active ingredients.

Description

Technical Field

[0001] The invention belongs to the technical field of local external preparations, and specifically relates to a bee sponge spicule gel and a preparation method and application thereof. Background Art

[0002] The skin is the largest organ in the human body. It is essentially a biomembrane barrier, which makes it difficult for most skin care active ingredients and drug molecules to penetrate and absorb through the skin. Therefore, it is extremely challenging to safely and effectively deliver drugs or active ingredients through the skin. Current physical penetration enhancement technologies, such as iontophoresis and ultrasonic penetration, are effective, but the treatment cost is high and they are not suitable for drug delivery to large areas of skin lesions. Chemical penetration enhancement technologies, including nanocarrier systems and chemical and polypeptide penetration enhancers, have also failed to fully meet the demand.

[0003] The sponge Haliclona sp. spicules (SHS) has a sharp tip, is stable and has high mechanical strength (SiO 2 The content is more than 95%), the shape is single and the size is uniform (length is about 120μm, diameter is about 7μm). It has a powdery appearance and can pass through a 200-mesh sieve, without generating the problem of solid sharp waste. As a new type of marine biomedical material, bee sponge spicules can be used for skin drug delivery and are expected to intervene in various skin-related fields, becoming an ideal dispersed biological microneedle. Summary of the invention

[0004] The invention aims to provide a bee sponge spicule gel.

[0005] Another object of the present invention is to provide a method for preparing the above-mentioned bee sponge spicule gel.

[0006] Another object of the present invention is to provide uses of the bee sponge spicule gel.

[0007] The technical solution of the present invention is as follows:

[0008] A bee sponge spicule gel is prepared from the following raw material components in percentage by weight: 1-4 wt% bee sponge spicules, 5-6 wt% propylene glycol, 0.5-0.8 wt% carbomer, 0.13-0.14 wt% sodium hydroxide, 0.2 wt% ethylparaben, and the remainder is deionized water, and the amount used is 10-20 mg / 1.5-2.0 cm 2 skin.

[0009] In a preferred embodiment of the present invention, the composition is made of the following raw material components in percentage by weight: 1 wt % bee sponge spicules, 5 w % propylene glycol, 0.6 w % carbomer, 0.13 w % sodium hydroxide, 0.2 w % ethylparaben, and the remainder is deionized water.

[0010] In a preferred embodiment of the present invention, the composition is made of the following raw material components in percentage by weight: 2 wt % bee sponge spicules, 6 w % propylene glycol, 0.8 w % carbomer, 0.14 w % sodium hydroxide, 0.2 w % ethylparaben, and the remainder is deionized water.

[0011] In a preferred embodiment of the present invention, the composition is made of the following raw material components in percentage by weight: 4wt% bee sponge spicules, 5w% propylene glycol, 0.5w% carbomer, 0.14w% sodium hydroxide, 0.2w% ethylparaben, and the remainder is deionized water.

[0012] The preparation method of the bee sponge spicule gel comprises the following steps:

[0013] (1) According to the above component formula and mass percentage, weigh each raw material component;

[0014] (2) Add propylene glycol, carbomer, and ethylparaben into deionized water and stir at 500 rpm for 30 min;

[0015] (3) After the carbomer is completely swollen, add sodium hydroxide and continue stirring at 500 rpm for 2 min until it becomes a gel;

[0016] (4) After adding the bee sponge spicules to the material obtained in step (3), continue stirring at 500 rpm for 5 minutes to fully mix.

[0017] The bee sponge spicule gel is used in the preparation of topical external preparation compositions, wherein the topical external preparations include skin care preparations, device gel preparations and pharmaceutical preparations.

[0018] A local external preparation composition, the active ingredient of which includes the bee sponge spicule gel.

[0019] The beneficial effects of the present invention are:

[0020] 1. The present invention uses a pressing and applying method to make the bee sponge spicules penetrate the stratum corneum of the skin at random angles, forming a large number of nano-scale micro-channels on the skin surface. These micro-channels can open the skin barrier and promote the percutaneous absorption of active ingredients.

[0021] 2. When the drug is applied to the skin through the present invention, the active ingredients or functional molecules can diffuse into the deep layers of the skin through these nanoscale microchannels, thereby improving the permeability and effectiveness of the drug. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 The conductivity change bar graph of the specific dose of bee sponge spicule gel prepared in Example 2 before and after massaging ex vivo pig skin with other matrices according to the experimental method in Example 4;

[0023] Figure 2 This is a comparison chart of the transdermal absorption of sodium fluorescein by a specific dose of bee sponge spicule gel prepared in Example 2 and a spicule emulsion of the same concentration according to the experimental method in Example 5. DETAILED DESCRIPTION

[0024] The technical solution of the present invention is further illustrated and described below through specific implementation modes in combination with the accompanying drawings.

[0025] Example 1

[0026] A bee sponge spicule gel, comprising, by mass percentage:

[0027] Bee sponge spicules 1%; propylene glycol 5%; carbomer 0.5%; sodium hydroxide 0.14%; ethylparaben 0.2%, the balance is deionized water.

[0028] The preparation method of the bee sponge spicule gel of this embodiment comprises the following steps:

[0029] (1) According to the above component formula and mass percentage, weigh each raw material component;

[0030] (2) Add propylene glycol, carbomer, and ethylparaben into deionized water and stir at 500 rpm for 30 min;

[0031] (3) After the carbomer is completely swollen, add sodium hydroxide and continue stirring at 500 rpm for 2 min until it becomes a gel;

[0032] (4) Add the bee sponge spicules to the material obtained in step (3), continue stirring at 500 rpm for 5 minutes, and mix thoroughly to obtain the product;

[0033] (5) Packaging of finished products.

[0034] Example 2

[0035] A bee sponge spicule gel, comprising, by mass percentage:

[0036] Bee sponge spicules 2%; propylene glycol 6%; carbomer 0.8%; sodium hydroxide 0.14%; ethylparaben 0.2%, the balance is deionized water.

[0037] The preparation method of the bee sponge spicule gel of this embodiment comprises the following steps:

[0038] (1) According to the above component formula and mass percentage, weigh each raw material component;

[0039] (2) Add propylene glycol, carbomer, and ethylparaben into deionized water and stir at 500 rpm for 30 min;

[0040] (3) After the carbomer is completely swollen, add sodium hydroxide and continue stirring at 500 rpm for 2 min until it becomes a gel;

[0041] (4) Add the bee sponge spicules to the material obtained in step (3), continue stirring at 500 rpm for 5 minutes, and mix thoroughly to obtain the product;

[0042] (5) Packaging of finished products.

[0043] Example 3

[0044] A bee sponge spicule gel, comprising, by mass percentage:

[0045] Bee sponge spicules 4%; propylene glycol 5%; carbomer 0.5%; sodium hydroxide 0.14%; ethylparaben 0.2%, the balance is deionized water.

[0046] The preparation method of the bee sponge spicule gel of this embodiment comprises the following steps:

[0047] (1) According to the above component formula and mass percentage, weigh each raw material component;

[0048] (2) Add propylene glycol, carbomer, and ethylparaben into deionized water and stir at 500 rpm for 30 min;

[0049] (3) After the carbomer is completely swollen, add sodium hydroxide and continue stirring at 500 rpm for 2 min until it becomes a gel;

[0050] (4) Add the bee sponge spicules to the material obtained in step (3), continue stirring at 500 rpm for 5 minutes, and mix thoroughly to obtain the product;

[0051] (5) Packaging of finished products.

[0052] Example 4

[0053] Taking the bee sponge spicule gel prepared in Example 2 as an example, the penetration-enhancing ability of bee sponge spicules in different matrices was tested by detecting the transcutaneous conductivity increase rate. The formulas of different matrices are as follows:

[0054] Emulsion A: 10% jojoba oil, 1% glyceryl monostearate, 2% dimethicone copolyol, and the balance deionized water; Preparation method: Heat jojoba oil, glyceryl monostearate, and dimethicone copolyol in a 70°C water bath until they are melted, heat deionized water to 70°C in another container, then mix the water phase and oil phase components at a speed of 1000 rpm, gradually cool to room temperature, and emulsify for 30 minutes.

[0055] Emulsion B: 5% glycerol, 5% shea butter, 1% glyceryl monostearate, 2% cetearyl alcohol, 2% ceteareth-20, and the balance deionized water; Preparation method: Heat shea butter, glyceryl monostearate, cetearyl alcohol, and ceteareth-20 in a 70°C water bath until they are melted, take another container and heat deionized water and glycerol to 70°C, then mix the water phase and oil phase components at a rotation speed of 1000 rpm, gradually cool to room temperature, and emulsify for 30 minutes.

[0056] This gel: The preparation method is the same as Example 2.

[0057] Aqueous gel: 1% sodium hyaluronate, 1% xanthan gum, and the balance deionized water; Preparation method: dissolve hyaluronic acid and xanthan gum in water, and stir thoroughly at 500 rpm for 30 minutes at room temperature.

[0058] Water cream: 5% caprylic / capric triglyceride, 3% glycerol, 2% PEG-100 stearate, 1% hyaluronic acid, and the balance deionized water; Preparation method: Heat caprylic / capric triglyceride and PEG-100 stearate in a 70°C water bath until melted, take another container and heat deionized water, glycerol and hyaluronic acid to 70°C and mix well, then mix the water phase and oil phase ingredients at a speed of 1000 rpm, gradually cool to room temperature, and emulsify for 30 minutes.

[0059] Aqueous solution: The aqueous solution system is deionized water.

[0060] First, intact pig skin was selected to measure the conductivity value, and then 20 mg and 100 mg of the bee sponge spicule gel prepared in Example 2 were weighed respectively. 2 The skin was manually massaged for 3 minutes, and then the gel on the surface was washed off, and the conductivity of the pig skin was measured again, which specifically included the following steps:

[0061] 1) Preliminary treatment of pig skin: Take fresh pig skin, remove the subcutaneous fat layer, shave the pig hair to a length of no longer than 2 mm, and use it immediately or freeze it at -20℃~-80℃ for later use.

[0062] 2) Use The pig skin of the same diameter was knocked out with a circular punch and installed on the Franz diffusion transdermal device. The skin conductivity change before and after the sponge spicule solution was measured by ex vivo skin transcutaneous resistance test. Before the sponge spicule solution was applied, the conductivity of the ex vivo pig skin was no higher than 10μA, indicating that the barrier function of the skin stratum corneum was intact and could be used for the next experiment.

[0063] 3) Weigh 20 mg and 100 mg of 2% spicule concentration of ① emulsion A, ② emulsion B, ③ gel, ④ aqueous gel, ⑤ water cream, and ⑥ aqueous solution, a total of six different matrix bee sponge spicule products, on an area of ​​1.77 cm 2 Manually massage the skin for 2-3 minutes until the product is completely absorbed by the skin, then wash off the residual spicules and measure the change in conductivity.

[0064] 4) The higher the conductivity change rate before and after massage, the better the penetration-enhancing performance of the bone needle. Figure 1 As shown, the conductivity change rate of the gel in Example 1 is the highest, proving that it has the best penetration-enhancing performance.

[0065] Example 5

[0066] Taking the bee sponge spicule gel prepared in Example 2 as an example, the transdermal ability of the bee sponge spicule gel and bee sponge spicule emulsion A (prepared in the same manner as emulsion A in Example 4) with the same bee sponge spicule concentration on the hydrophilic drug model sodium fluorescein was compared. The specific implementation scheme is as follows:

[0067] 1) Preliminary treatment of pig skin: Take fresh pig skin, remove the subcutaneous fat layer, shave the pig hair to a length of no longer than 2 mm, and use it immediately or freeze it at -20℃~-80℃ for later use.

[0068] 2) Use The pig skin of the same diameter was knocked out with a circular punch and installed on the Franz diffusion transdermal device. The skin conductivity change before and after the sponge spicule solution was measured by ex vivo skin transcutaneous resistance test. Before the sponge spicule solution was applied, the conductivity of the ex vivo pig skin was no higher than 10μA, indicating that the barrier function of the skin stratum corneum was intact and could be used for the next experiment.

[0069] 3) Sodium fluorescein was used as a drug model and dissolved in the bee sponge spicule gel prepared in Example 2 and the above emulsion system at a concentration of 0.2%, and then 20 mg was weighed and placed on an area of ​​1.77 cm 2 Manually massage the skin for 2 minutes.

[0070] 4) Place the massaged skin in a transdermal pool and perform transdermal transdermal treatment in a 37°C water bath for 16 hours in the dark.

[0071] 5) After 16 hours of in vitro transdermal perfusion, the transdermal pool was removed, and the drug delivery cavity was rinsed with ultrapure water for 5 times to wash away the residual skin care products and collect the liquid in the receiving pool.

[0072] 6) Remove the pig skin, knock off the drug-administered part and fix it on the stripping device, and use the tape stripping method to strip it ten times to collect the stratum corneum sample. Then use a scalpel to scrape the epidermis and mince the dermis, divide it into brown glass bottles, and add 4 mL of methanol-PBS (volume ratio 1:1) mixture.

[0073] 7) Place on a shaker at 25°C, 180 r / min and extract for 24 h.

[0074] 8) Then, take 1 mL of the extract in a centrifuge tube and centrifuge at 5000 rpm for 5 min. Take 200 μl of the supernatant after centrifugation and place it in a black 96-well plate. Set up 3 copies in parallel (the liquid taken out of the receiving pool is operated in the same way as above). Use an ELISA reader with an excitation wavelength of 485 nm and an emission wavelength of 535 nm to measure the fluorescence value and calculate the drug absorption rate in each cortex. The results are as follows: Figure 2 shown.

[0075] The above description is only a preferred embodiment of the present invention, and therefore cannot be used to limit the scope of the present invention. That is, equivalent changes and modifications made according to the patent scope of the present invention and the contents of the specification should still fall within the scope of the present invention.

Claims

1. A bee sponge spicule gel, characterized in that: The invention is prepared from the following raw material components in the following mass percentages: 1-4wt% bee sponge spicules, 5-6w% propylene glycol, 0.5-0.8w% carbomer, 0.13-0.14w% sodium hydroxide, 0.2w% ethylparaben, and the balance is deionized water, and the usage is 10-20mg / 1.5-2.0cm 2 skin.

2. The bee sponge spicule gel according to claim 1, characterized in that: The invention is prepared from the following raw material components in percentage by weight: 1wt% bee sponge spicules, 5w% propylene glycol, 0.6w% carbomer, 0.13w% sodium hydroxide, 0.2w% ethylparaben, and the balance is deionized water.

3. The bee sponge spicule gel according to claim 1, characterized in that: The invention is prepared from the following raw material components in percentage by weight: 2wt% bee sponge spicules, 6w% propylene glycol, 0.8w% carbomer, 0.14w% sodium hydroxide, 0.2w% ethylparaben, and the balance is deionized water.

4. The bee sponge spicule gel according to claim 1, characterized in that: The invention is prepared from the following raw material components in percentage by weight: 4wt% bee sponge spicules, 5w% propylene glycol, 0.5w% carbomer, 0.14w% sodium hydroxide, 0.2w% ethylparaben, and the balance is deionized water.

5. The method for preparing the bee sponge spicule gel according to any one of claims 1 to 4, characterized in that: The steps include: (1) According to the above component formula and mass percentage, weigh each raw material component; (2) Add propylene glycol, carbomer, and ethylparaben into deionized water and stir at 500 rpm for 30 min; (3) After the carbomer is completely swollen, add sodium hydroxide and continue stirring at 500 rpm for 2 min until it becomes a gel; (4) After adding the bee sponge spicules to the material obtained in step (3), continue stirring at 500 rpm for 5 minutes to fully mix.

6. Use of the bee sponge spicule gel according to claim 1 in preparing a topical external preparation composition.

7. A topical preparation composition, characterized in that: The effective ingredients thereof include the bee sponge spicule gel described in any one of claims 1 to 4.

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