Application of bee sponge spicule in preparation of permeation enhancing composition

Abstract

The invention discloses application of a bee sponge bone needle in preparation of a penetration enhancing composition. The length of the bee sponge bone needle is 110-140 microns. Compared with other freshwater sponge spicules, the bee sponge spicule can better overcome skin barriers and promote absorption of drugs or active ingredients.

Description

Technical Field

[0001] The invention belongs to the technical field of medicines, and in particular relates to the use of bee sponge spicules in preparing a penetration-enhancing composition. Background Art

[0002] The skin is the largest organ in the human body and is one of the most direct routes of drug administration. Compared with other routes of administration (such as oral administration, injection, etc.), skin administration has many unique advantages, including avoiding the first-pass effect of the liver, damage to the gastrointestinal tract, and possible infection and pain caused by injection. In addition, skin administration can directly act on the local lesions of the skin to achieve sustained or controlled release, reduce adverse drug reactions, and terminate administration at any time, thereby greatly improving the convenience and compliance of patient treatment.

[0003] However, the skin is essentially a biological membrane barrier, and most drug molecules have difficulty penetrating the skin for absorption. Therefore, safe and effective transdermal delivery of drugs or active ingredients is a very challenging task. Although current physical penetration enhancement technologies, such as iontophoresis and ultrasonic introduction, are effective, the treatment cost is high and they are not suitable for administration to large areas of skin lesions. Although chemical penetration enhancement technologies, including nanocarrier systems, chemical and polypeptide penetration enhancers, have made some progress in improving drug transdermal absorption, their penetration enhancement effect still needs to be further improved. Summary of the invention

[0004] The present invention aims to overcome the defects of the prior art and provide the use of bee sponge spicules in preparing a penetration-enhancing composition.

[0005] Another object of the present invention is to provide a penetration-enhancing composition.

[0006] The technical solution of the present invention is as follows:

[0007] Use of bee sponge spicules in preparing a penetration-enhancing composition, wherein the bee sponge spicules have a length of 110-140 μm and a diameter of 5.5-9.0 μm.

[0008] In a preferred embodiment of the present invention, the bee sponge spicules have a length of 114-133 μm and a diameter of 5.9-8.3 μm.

[0009] More preferably, the dosage of the bee sponge spicule is 9-11 mg per 1.7-1.9 cm 2 skin.

[0010] A penetration-promoting composition, the effective component of which includes bee sponge spicules with a length of 110-140 μm and a diameter of 5.5-9.0 μm.

[0011] In a preferred embodiment of the present invention, the bee sponge spicules have a length of 114-133 μm and a diameter of 5.9-8.3 μm.

[0012] Further preferably, the active ingredient is the bee sponge spicule.

[0013] More preferably, the dosage of the bee sponge spicule is 9-11 mg per 1.7-1.9 cm 2 skin.

[0014] The beneficial effect of the present invention is that the bee sponge spicules of the present invention can better overcome the skin barrier and promote the absorption of drugs or active ingredients compared with other freshwater sponge spicules. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 10 mg of different sponge spicules in Example 1 of the present invention at 1.77 cm 2 The bar graph of the increase rate of the ex vivo pig skin conductivity after manual massage of the ex vivo pig skin surface area for 3 minutes. Among them, the increase value of the conductivity of the honey sponge spicule (SHS) was the highest, which was 78.33±5.69, followed by SP330, which increased by 62.10±7.55, SP250, which increased by 25.67±5.51, and SP200, which increased the least, which was 18.42±6.13.

[0016] Figure 2 10 mg of different sponge spicules in Example 2 of the present invention at 1.77 cm 2 After manually massaging the surface of the ex vivo pig skin for 3 minutes, the scanning electron microscopy image of the ex vivo pig skin showed that different numbers of bone needles were distributed on the three-dimensional pig skin surface of different groups.

[0017] Figure 3 10 mg of different sponge spicules in Example 2 of the present invention at 1.77 cm 2 The number of bone needles per unit area of ​​ex vivo pig skin after manual massage of the ex vivo pig skin surface for 3 minutes is shown in the bar graph. 2 In the ex vivo pig skin, the number of punctures of SHS was the largest, which was 9.2±1.4, followed by SP330, which was 3.0±0.0, SP250, which was 1.6±1.13, and SP200, which was 1.0±0.0. Figure 1 The results for the conductivity increase rate in .

[0018] Figure 4 10 mg of different sponge spicules in Example 2 of the present invention at 1.77 cm 2The depth of the sponge spicules in the ex vivo pig skin was statistically analyzed after the surface of the ex vivo pig skin was manually massaged for 3 minutes. It can be seen that the depth of the sponge spicules in the skin is related to the length of the sponge spicules themselves, among which: the penetration depth of SHS is 34.7±18.9μm, and the penetration depth accounts for 28.9% of the spicule length; the penetration depth of SP200 is 106.4±26.5μm, and the penetration depth accounts for 53.1% of the spicule length; the penetration depth of SP250 is 125.6±24.9μm, and the penetration depth accounts for 50.2% of the spicule length; the penetration depth of SP330 is 155.0±71.4μm, and the penetration depth accounts for 46.9% of the spicule length.

[0019] Figure 5 This is a statistical bar chart of the number of sponge spicules per unit weight (per gram) in Example 3 of the present invention. Among them: the content of sponge spicules per unit weight of SHS is 5*10 7 root / g, SP200 unit weight spicule content is 9.06*10 6 root / g, SP250 unit weight spicule content is 1.98*10 7 root / g, SP330 unit weight spicule content is 1.32*10 7 root / g.

[0020] Figure 6 The statistical bar graphs of the average length and diameter of the four sponge spicules in Examples 1 to 3 of the present invention are shown in FIG. Among them, the average length and diameter of SHS are 123.34±8.90 μm and 7.07±1.17 μm, respectively; the average length and diameter of SP200 are 213.31±18.53 μm and 11.46±1.74 μm, respectively; the average length and diameter of SP250 are 243.67±12.68 μm and 11.18±2.44 μm, respectively; and the average length and diameter of SP330 are 323.84±21.95 μm and 11.03±2.08 μm, respectively. DETAILED DESCRIPTION

[0021] The technical solution of the present invention is further illustrated and described below through specific implementation modes in combination with the accompanying drawings.

[0022] Example 1

[0023] The skin was massaged using a bee sponge spicule (SHS) with a length of 120 μm and freshwater sponge spicules (SP200, SP250 and SP330) with lengths of 200 μm, 250 μm and 330 μm respectively (the specifications of different sponge spicules are shown in Figure 2). Figure 6 First, intact pig skin was selected to measure the conductivity value, and then 10 mg of three bone needles were weighed and mixed with 0.5 g of gel. 2The skin was manually massaged for 3 minutes, the gel on the surface was washed off, and the conductivity of the pig skin was measured again.

[0024] 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.

[0025] 2) Use a φ40mm round puncher to knock out pig skin of the same diameter, install it on the Franz diffusion transdermal device, and use the in vitro skin transcutaneous resistance test to measure the changes in skin conductivity before and after the sponge spicule solution is applied. Before the sponge spicule is applied, the conductivity of the in vitro pig skin is no higher than 10μA, which indicates that the barrier function of the skin stratum corneum is intact and can be used for the next experiment.

[0026] 3) Use bee sponge spicules with a length of 120 μm and freshwater sponge spicules with lengths of 200 μm, 250 μm, and 330 μm to massage the skin. Weigh 10 mg of each type of spicule and place them on an area of ​​1.77 cm 2 The skin was manually massaged for 3 min, and then the conductivity change was measured.

[0027] 4) The higher the conductivity change rate before and after massage, the better the penetration-promoting performance of the bone needle. Figure 1 shown.

[0028] Example 2

[0029] The bee sponge spicules (SHS) with a length of 120 μm and freshwater sponge spicules (SP200, SP250 and SP330) with lengths of 200 μm, 250 μm and 330 μm were used (the specifications of different sponge spicules are shown in Figure 6 The skin was massaged and then a scanning electron microscope was taken to count the number and depth of bone needles inserted per unit area.

[0030] 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.

[0031] 2) Use a φ40mm round puncher to knock out pig skin of the same diameter, install it on the Franz diffusion transdermal device, and use the in vitro skin transcutaneous resistance test to measure the changes in skin conductivity before and after the sponge spicule solution is applied. Before the sponge spicule is applied, the conductivity of the in vitro pig skin is no higher than 10μA, which indicates that the barrier function of the skin stratum corneum is intact and can be used for the next experiment.

[0032] 3) Use bee sponge spicules with a length of 120 μm and freshwater sponge spicules with lengths of 200 μm, 250 μm, and 330 μm to massage the skin. Weigh 10 mg of each type of spicule and place them on an area of ​​1.77 cm2 Manually massage the skin for 3 minutes.

[0033] 4) Rinse with PBS five times to remove the remaining spicules, then take scanning electron microscope photos to count the number and depth of spicules per unit area.

[0034] 5) The more bone needles that penetrate the skin per unit area, the stronger the penetration-promoting ability of the bone needles. Figures 2 to 4 shown.

[0035] Example 3

[0036] The number of bone needles per unit weight is counted. Theoretically, the more bone needles per unit weight, the more microchannels can be formed, so it has a higher penetration-promoting effect. The specific operation is as follows:

[0037] 1) Accurately weigh 0.1 g of 120 μm-long honey sponge spicules (SHS) and 200 μm, 250 μm, and 330 μm-long freshwater sponge spicules (SP200, SP250, and SP330) (the specifications of different sponge spicules are shown in the table below). Figure 6 shown).

[0038] 2) Place the above bone needles into 100 ml of pure water, stir and dilute thoroughly, then pipette 10 μL of the solution and drop it onto a glass slide.

[0039] 3) Count the number of spicules under a microscope and then convert the number to obtain the number of spicules per gram.

[0040] 4) Theoretically, the more spicules there are per unit weight, the more microchannels can be formed. Figure 5 shown.

[0041] 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. Use of bee sponge spicules in preparing a penetration-enhancing composition, characterized in that: The bee sponge spicule has a length of 110-140 μm and a diameter of 5.5-9.0 μm.

2. The use according to claim 1, characterized in that: The length of the bee sponge spicule is 114-133 μm and the diameter is 5.9-8.3 μm.

3. The use according to claim 2, characterized in that: The dosage of the bee sponge spicule is 9-11 mg per 1.7-1.9 cm 2 skin.

4. A penetration-enhancing composition, characterized in that: Its active ingredients include bee sponge spicules with a length of 110-140 μm and a diameter of 5.5-9.0 μm.

5. A penetration-enhancing composition according to claim 4, characterized in that: The length of the bee sponge spicule is 114-133 μm and the diameter is 5.9-8.3 μm.

6. A penetration-promoting composition according to claim 4 or 5, characterized in that: The effective ingredient is the bee sponge spicule.

7. A penetration-enhancing composition according to claim 6, characterized in that: The dosage of the bee sponge spicule is 9-11 mg per 1.7-1.9 cm 2 skin.

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