CN112022919A

CN112022919A - Percutaneous-absorption artemisia vulgaris oil carrier gel and preparation method thereof

Info

Publication number: CN112022919A
Application number: CN202010698506.XA
Authority: CN
Inventors: 马云淑; 张昆; 熊磊; 李亶烨; 程欣; 高家菊; 刘云宽
Original assignee: Yunnan University of Traditional Chinese Medicine TCM
Current assignee: Yunnan University of Traditional Chinese Medicine TCM
Priority date: 2020-07-20
Filing date: 2020-07-20
Publication date: 2020-12-04

Abstract

The invention provides a percutaneous-absorption gel of a wormwood oil carrier and a preparation method thereof. The composition is prepared from the following components in parts by mass: artemisia vulgaris oil15-150 parts of a transfersome, 5-15 parts of a gel matrix, 30-150 parts of normal saline, 10-50 parts of a humectant and 3-10 parts of a pH value regulator. The xanthium and wormwood oil carrier gel prepared by the invention can obviously add medicine in-vitro accumulated permeation quantity after transdermal administration, and improve C absorbed by the skin in the rat body_max、AUC_0‑t、AUC_0‑∞The medicine has the advantages of improving the bioavailability of the medicine, prolonging the action time of the medicine, avoiding the problems of short action time, poor stability, poor patient compliance, easy leakage of the xanthium oil transfersome, easy loss of transdermal administration liquid, low medicine-loading rate of the xanthium oil transfersome patch, uneven medicine release and the like by selectively applying or pasting the medicine on the part when in use, covering the bad smell of the medicine and having no stimulation to the skin.

Description

Percutaneous-absorption artemisia vulgaris oil carrier gel and preparation method thereof

Technical Field

The invention relates to the technical field of medicines, in particular to a percutaneous-absorption gel of a xanthium oil carrier and a preparation method thereof.

Background

The xanthium oil is compound essential oil extracted from seven medicinal materials of rhizoma atractylodis, folium artemisiae argyi, agastache rugosus, eupatorium, clove, pepper and the like, the main components of the xanthium oil are eugenol (38.42%), 1, 8-cineole (12.13%), beta-caryophyllene (9.79%) and the like, and the xanthium oil is mainly administrated by nasal drip and spray clinically at present and is used for treating upper respiratory tract infection diseases of children. The early-stage research shows that the compound has better antibacterial activity, has stronger killing effect on staphylococcus aureus, escherichia coli, beta hemolytic streptococcus and candida albicans, and has certain inhibiting effect on pseudomonas aeruginosa. In recent researches, morrhizus finds that the wormwood oil can reduce the content of IL-1 beta, effectively inhibit the inflammatory reaction of the rat with the lung qi deficiency type and improve the T cell subgroup CD4 of the rat with the lung qi deficiency type⁺/CD8⁺The ratio of (a) to (b), promoting the regulation of cellular immunity. Further study results show that Artemisia xanthium oil can improve CUMS-induced depression-like behavior in rat brain and regulate DA and 5-HT metabolism.

The transdermal drug delivery system refers to a mode of drug delivery through the skin, in which the drug passes through the stratum corneum of the skin to the dermis layer at a constant speed or nearly at a constant speed, and is absorbed by the capillary vessels to enter the systemic circulation to produce local or systemic effects, and is one of the key points and hot spots of the development and research of third-generation pharmaceutical preparations after tablets and injections. Compared with other administration modes, the transdermal drug delivery has the characteristics of avoiding the first pass effect of the liver of the drug and the damage of the gastrointestinal tract to the drug, prolonging the action time of the drug, improving the compliance of patients, interrupting the drug delivery at any time and the like. Common transdermal drug delivery preparations comprise transdermal patches, gels, cataplasms, creams, tinctures and the like, wherein the gels are widely concerned due to the characteristics of high drug loading capacity, good drug compatibility, simple preparation process, strong skin compliance, convenient use and the like. The carrier is also called flexible nano liposome, is a special liposome which is easy to deform and is firstly proposed by Cevc G and the like. The cholate and polysorbate surfactants are used as edge activators during preparation, so that the outer wall bilayer has good deformability, can penetrate through a pore canal which is several times smaller than the bilayer, can penetrate through a pore canal of a skin stratum corneum with the diameter of about 0.4nm, is expected to become a transdermal carrier with good macromolecule and micromolecule medicines and fat-soluble and water-soluble medicines, can obviously improve the transdermal permeation amount of the medicines, and has the effect of improving the stability of volatile oil molecules. In recent studies, it is often incorporated into a gel matrix to prepare a carrier gel, thereby increasing the transdermal absorption of the drug.

The existing Artemisia vulgaris oil nasal administration preparation mainly comprises Artemisia vulgaris incense oil, Artemisia vulgaris oil nasal microspheres and Artemisia vulgaris oil nasal inclusion compound gel. The Zhao Dan takes gelatin and Arabic gum as carriers, and prepares the xanthium oil nasal microspheres with round shape and uniform particle size by an emulsification crosslinking method, and the result shows that the stability of the medicament can be obviously improved after the xanthium oil is prepared into the microspheres, but the xanthium oil microspheres have low medicament encapsulation rate and small medicament loading amount, and meanwhile, the medicament is relatively difficult to be retained in a nasal cavity to play the medicament effect when the medicament is administrated in the nasal cavity, so that the bioavailability of the medicament is low. On the basis, the xanthium oil is prepared into hydroxypropyl-beta-CD inclusion compound in-situ gel in the Huangqiyan way, and research results show that the inclusion compound in-situ gel improves MRT and AUC absorbed by the xanthium oil in nasal cavityHowever, the xanthate mugwort oil nasal inclusion compound in-situ gel still has short drug action time (T) in practical application_max5min), inconvenient administration, poor patient compliance and the like, and for depression, lung qi deficiency and other diseases which require the medicament to slowly exert the treatment effect for a long time, the nasal administration also has certain limitation, so further improvement is needed.

In recent research, a xanthium oil transfersome which has high encapsulation efficiency and good stability and can promote the percutaneous absorption of the medicine is prepared by a film ultrasonic method, a xanthium oil transfersome patch which takes an acrylate pressure-sensitive adhesive Eudragit E100 as a main matrix is prepared on the basis, and an in-vitro percutaneous permeation experiment is carried out by taking a common xanthium oil patch in parallel contrast. The results show that: the cumulative permeation quantity of the xanthium oil patch in unit area of 72h eugenol is 0.1956 +/-0.0659 mg cm^－2Is 1.4931 times of the xanthium oil transfersome patch, and the steady-state transdermal permeation rate Jss of the xanthium oil patch is 0.0480 +/-0.0056 mg-cm^-2·h^-1/21.3953 times of the patch of Artemisia xanthium oil transfersome, the two have significant difference (P)<0.05). The result shows that the release of the drug can be slowed and controlled to a certain extent after the artemisia xanthioides oil is prepared into the transfersome patch. However, the patch of the artemisia xanthium oil carrier has low drug loading rate and relatively slow drug absorption rate after transdermal administration, so that a better transdermal administration preparation for promoting the transdermal absorption of the artemisia xanthium oil is needed to be found.

Disclosure of Invention

Aiming at the defects of the xanthium oil preparation, the invention provides a percutaneous absorption xanthium oil transfersome gel which has simple preparation process, good biocompatibility and no skin prick and a preparation method thereof.

The invention is realized by the following technical scheme: a percutaneous absorption xanthium oil carrier gel is characterized by being prepared from the following components in parts by mass:

the gel is one or more of carbomer gel, chitosan gel and cellulose gel, and the mixing ratio of the gel to the chitosan gel is arbitrary.

The humectant is one or more of glycerol, propylene glycol, betaine and hyaluronic acid, and the mixing ratio of the components is arbitrary.

The pH value regulator is one or two of triethanolamine and sodium hydroxide, and the mixing ratio of the triethanolamine and the sodium hydroxide is any combination.

The invention provides a percutaneous absorption gel of a wormwood oil carrier, which is prepared by the following process steps:

1) preparing the following components in parts by mass:

2) uniformly mixing the xanthium and wormwood oil transfersome obtained in the step 1) with normal saline to obtain a phase I;

3) adding the phase I obtained in the step 2) into the gel while stirring, uniformly mixing, and carrying out sealed swelling for 10-15 h at the temperature of 2-6 ℃ to obtain a phase II;

4) adding the phase II obtained in the step 3) into a humectant while stirring, and grinding and uniformly mixing to form a gel-like substance;

5) adding a pH value regulator into the gel-like substance obtained in the step 4), grinding and uniformly mixing to obtain the percutaneous absorption xanthium oil carrier gel.

The xanthium oil carrier gel is directly smeared on the skin according to clinical requirements when in use, or is uniformly paved on a blank cataplasm patch and then is pasted on the skin; the blank cataplasm patch is medical non-woven fabric film-added anti-seepage plaster cloth and consists of a medicine-carrying ring, a sticking layer and an anti-sticking layer.

The xanthium oil transfersome is prepared from the following components in parts by mass:

the membrane material is one or a combination of more of soybean lecithin, dipalmitoyl phosphatidylcholine and cholesterol, and the combination proportion of the more is arbitrary.

The membrane softener is one or a combination of more of sodium cholate, sodium deoxycholate, propylene glycol, ethanol, tween and span, and the combination proportion of the more is arbitrary.

The xanthium oil carrier is prepared by the following method:

a1, adding the film material into petroleum ether according to the mass/volume ratio of the film material to the petroleum ether of 1: 10-30 to completely dissolve the film material, so as to obtain petroleum ether solution;

a2, transferring the petroleum ether solution prepared in the step A1 into a container, and removing the petroleum ether by decompression and rotation to form a film on the wall of the container;

a3, adding a film softener into deionized water, and carrying out ultrasonic treatment in an ultrasonic cleaning machine, wherein the ultrasonic power is 250W, and the ultrasonic treatment time is 5-10 min, so as to obtain a film softener aqueous solution with the mass concentration of 3-200 mg/mL;

a4, adding xanthium oil into a film softener aqueous solution according to the mass ratio of 1: 10-30, and carrying out ultrasonic treatment in an ultrasonic processor with the ultrasonic power of 60-120W for 2-6 min to obtain a xanthium oil suspension;

a5, adding the xanthium oil suspension obtained in the step A4 into a container for preparing the film obtained in the step A2 according to the mass ratio of the film to the xanthium oil suspension of 1: 20-40, and carrying out hydration washing on the film for 1-3 hours under the water bath condition of 30-50 ℃ to obtain the xanthium oil carrier suspension;

a6, carrying out ultrasonic treatment on the xanthium oil transfersome suspension obtained in the step A5 in an ultrasonic processor, wherein the ultrasonic power is 60-120W, the ultrasonic treatment time is 2-6 min, and then filtering through a 0.22-micron microporous filter membrane to obtain the xanthium oil transfersome.

And D, refrigerating the artemisia vulgaris oil carrier obtained in the step A6 at 4 ℃ for later use.

Compared with the prior art, the invention has the following advantages and beneficial effects:

1) after the artemisia xanthioides oil is prepared into the artemisia xanthioides oil carrier gel, the water solubility and the stability of the artemisia xanthioides oil are improved, meanwhile, the bad smell of the medicine is covered, and after the artemisia xanthioides oil carrier gel is applied to the in-vitro skin of a mouse, the accumulated permeation amount of the artemisia xanthioides oil can be obviously increased;

2) the gel of the Artemisia xanthium oil transfersome is prepared, and after the SD rat is administrated percutaneously, C of the Artemisia xanthium oil in the rat can be remarkably increased_max、AUC_0-t、AUC_0-∞Compared with the artemisia vulgaris oil gel, the percutaneous administration preparation has the advantages that the relative bioavailability of the artemisia vulgaris oil is remarkably improved;

3) the preparation process of the gel is simple, and the prepared gel has good biocompatibility and no irritation to skin by means of medicinal penetration promotion;

4) the gel of the artemisia vulgaris oil carrier effectively solves the problems of short action time, inconvenient administration, low patient compliance and the like of artemisia vulgaris oil nasal cavity inhalation administration medicines; meanwhile, the problems that the medicine directly applied to the skin by the xanthium oil transfersome is easy to leak, the medicine loading rate of the transdermal administration of the xanthium oil transfersome patch is low, the absorption rate is slow and the like are solved;

5) the gel of the artemisia vulgaris oil carrier is milky-white gel, and effectively solves the problem of oil bleeding of the artemisia vulgaris oil gel.

Drawings

FIG. 1 is a conventional gel of Artemisia xanthium oil;

FIG. 2 is a gel of Artemisia xanthium oil carrier of the present invention;

FIG. 3 is a curve of in vitro transdermal permeation of a gel of Artemisia xanthium oil carrier;

FIG. 4 is a blood concentration-time curve of a xanthium oil carrier gel.

Detailed Description

The present invention is further described with reference to the following specific examples, but the present invention is not limited to these examples, and any techniques realized based on the above-described contents of the present invention fall within the scope of the present invention.

Example 1

Preparing a xanthium oil carrier:

A. preparing the following materials in parts by mass:

a1, putting 8.3 parts of soybean lecithin and 1.4 parts of cholesterol into a 10mL centrifuge tube, adding 166.7 parts of petroleum ether, and ultrasonically dissolving in a 250W ultrasonic cleaning machine for 10min to obtain a uniform petroleum ether solution;

a2, transferring the petroleum ether solution into a 50mL pear-shaped bottle, and rotating and decompressing to volatilize the petroleum ether, namely forming a uniform lipid film on the wall of the pear-shaped bottle;

a3, adding 0.5 part of sodium cholate and 16.7 parts of propylene glycol into 123.1 parts of deionized water, and carrying out ultrasonic treatment in a 250W ultrasonic cleaning machine for 10min to dissolve the sodium cholate and the propylene glycol in water to obtain a film softener aqueous solution;

a4, adding 16.7 parts of xanthium oil into an aqueous solution of a membrane softener, and carrying out ultrasonic treatment for 4min (On time:2 s; Off time:2s) in a 120W ultrasonic processor to obtain a uniform milky xanthium oil suspension;

a5, adding the xanthium sibiricum oil suspension into the pear-shaped bottle with the film formed in the step A2, and hydrating and washing the film for 1h under the water bath condition of 45 ℃ to obtain the xanthium sibiricum oil carrier suspension;

a6, carrying out ultrasonic treatment On the suspension of the xanthium oil transfersome in a 120W ultrasonic processor for 4min (On time:2 s; Off time:2s), filtering through a 0.22 mu m microporous membrane to obtain the xanthium oil transfersome, sealing and refrigerating at 4 ℃ for later use.

Example 2

Preparation of Artemisia xanthium oil carrier

B. Preparing the following materials in parts by mass:

b1, putting 10.0 parts of soybean lecithin and 1.7 parts of cholesterol into a 10mL centrifuge tube, adding 166.7 parts of petroleum ether, and ultrasonically dissolving in a 250W ultrasonic cleaning machine for 10min to obtain a uniform petroleum ether solution;

b2, transferring the petroleum ether solution into a 50mL pear-shaped bottle, and performing reduced pressure rotation to volatilize the petroleum ether, namely forming a thin film on the wall of the pear-shaped bottle;

b3, adding 0.67 part of sodium cholate and 25.0 parts of propylene glycol into 103.6 parts of deionized water, and carrying out ultrasonic treatment for 10min in a 250W ultrasonic cleaning machine to dissolve the sodium cholate and the propylene glycol into water to obtain a uniform membrane softener aqueous solution;

b4, adding 25.0 parts of xanthium oil into the aqueous solution of the membrane softener, and carrying out ultrasonic treatment for 4min (On time:2 s; Off time:2s) in a 120W ultrasonic processor to obtain milky xanthium oil suspension;

b5, adding the xanthium oil suspension into the pear-shaped bottle with the film formed in the step B2, and hydrating and washing the film for 1h under the water bath condition of 45 ℃ to obtain the xanthium oil carrier suspension;

b6, carrying out ultrasonic treatment On the xanthium oil transfersome suspension in a 120W ultrasonic processor for 4min (On time:2 s; Off time:2s), filtering through a 0.22 mu m microporous filter membrane to obtain the xanthium oil transfersome, sealing and refrigerating at 4 ℃ for later use.

Example 3

Preparation of Artemisia xanthium oil carrier

C. Preparing the following materials in parts by mass:

c1, putting 11.7 parts of soybean lecithin and 1.9 parts of cholesterol into a 10mL centrifuge tube, adding 166.7 parts of petroleum ether, and ultrasonically dissolving in a 250W ultrasonic cleaning machine for 10min to obtain a uniform petroleum ether solution;

c2, transferring the petroleum ether solution into a pear-shaped bottle, and rotating to reduce pressure to volatilize the petroleum ether, namely forming a thin film on the bottle wall of the pear-shaped bottle;

c3, adding 0.8 part of sodium cholate and 33.3 parts of propylene glycol into 85.7 parts of deionized water, and ultrasonically dissolving the mixture in a 250W ultrasonic cleaning machine for 10min to dissolve the sodium cholate and the propylene glycol in the water to obtain a uniform membrane softener aqueous solution;

c4, adding 33.3 parts of xanthium oil into the aqueous solution of the membrane softener, and carrying out ultrasonic treatment for 4min (On time:2 s; Off time:2s) in a 120W ultrasonic processor to obtain milky xanthium oil suspension;

c5, adding the xanthium sibiricum oil suspension into the pear-shaped bottle which forms the film in the step C2, and hydrating and washing the film for 1h under the water bath condition of 45 ℃ to obtain the xanthium sibiricum oil carrier suspension;

and C6, carrying out ultrasonic treatment On the xanthium oil transfersome suspension in an ultrasonic processor with the power of 120W for 4min (On time:2 s; Off time:2s), filtering through a 0.22 mu m microporous membrane to obtain the xanthium oil transfersome, sealing and refrigerating at 4 ℃ for later use.

The encapsulation efficiency, particle size, Zeta potential and polydispersity values of the xanthium oil transfersomes obtained in examples 1, 2 and 3 are shown in table 1. The results show that the particle size, encapsulation efficiency, Zeta potential and polydispersity index of the xanthium oil transfersomes of the examples 1-3 have no significant difference, and the xanthium oil transfersomes prepared in the prescription range are stable and feasible.

TABLE 1 characterization results of Artemisia xanthium oil transfersomes prepared under different prescriptions (n ═ 3)

Example 4

Preparation of Artemisia xanthium oil carrier gel

D. Preparing the following components in parts by mass:

d1, taking 125.0 parts of the xanthium oil transfersome in the embodiment 1, adding 50.0 parts of normal saline, and uniformly mixing to obtain a phase I;

d2, adding the phase I into 6.7 parts of carbomer gel matrix under stirring, uniformly mixing, and sealing and swelling at 4 ℃ for 12 hours to obtain a phase II;

d3, adding 16.7 parts of glycerol into the phase II under stirring, and grinding and uniformly mixing to obtain a milky gel;

d4, adding 5.0 parts of triethanolamine into the milky white gel to adjust the pH value to 6.5, grinding and mixing uniformly to obtain uniform milky white Artemisia vulgaris oil carrier gel shown in figure 2.

Example 5

Preparation of Artemisia xanthium oil carrier gel

E. Preparing the following components in parts by mass:

e1, mixing 62.5 parts of the xanthium oil transfersome in the embodiment 2 with 106.4 parts of normal saline uniformly to obtain a phase I;

e2, adding the phase I into 8.5 parts of carbomer gel matrix under stirring, uniformly mixing, and sealing and swelling at 4 ℃ for 12 hours to obtain a phase II;

e3, adding 20.0 parts of glycerol into the phase II under stirring, and grinding and uniformly mixing to obtain a milky gel;

e4, adding 6.0 parts of triethanolamine into the milky white gel, adjusting the pH value to 6.5, grinding and mixing uniformly to obtain uniform milky white Artemisia vulgaris oil carrier gel.

Example 6

Preparation of Artemisia xanthium oil carrier gel

F. Preparing the following components in parts by mass:

f1, taking 31.3 parts of the xanthium oil transfersome in the embodiment 3, and adding 125.1 parts of normal saline to be uniformly mixed to obtain a phase I;

f2, adding the phase I into 10.0 parts of carbomer gel matrix under stirring, uniformly mixing, and sealing and swelling at 4 ℃ for 12 hours to obtain a phase II;

f3, adding 30.0 parts of glycerol into the phase II under stirring, and grinding and uniformly mixing to obtain a milky gel;

f4, adding 7.0 parts of triethanolamine into the milky white gel to adjust the pH value to 6.5, and grinding and mixing uniformly to obtain the uniform milky white Artemisia ordosica oil carrier gel.

The gel of the oil transfer medium of artemisia xanthium prepared in example 4, example 5 and example 6 was subjected to comprehensive scoring according to the scoring rules in table 2, with adhesion and stability as main evaluation indexes. The results show that the comprehensive scores of the gel of the xanthium sibiricum oil transfersome prepared in the examples 4-6 are respectively 87.67 +/-2.32, 87.42 +/-3.27 and 86.48 +/-2.98, and the gel of the xanthium sibiricum oil transfersome prepared in the prescription range has better adhesiveness and stability, and the preparation prescription is stable and feasible.

TABLE 2 gel evaluation index of Artemisia xanthium oil carrier

Example 7

Preparation of gel plaster of Artemisia xanthium oil carrier

And (3) uncovering the anti-adhesion layer of the blank gel cataplasm patch to expose the medicine carrying ring, uniformly spreading 167.0 parts of the xanthium oil carrier gel of the example 4 on the medicine carrying ring, and covering the anti-adhesion layer to obtain the xanthium oil carrier gel patch.

The effect of the invention is verified by the following experimental examples:

experimental example 1 gel in vitro percutaneous permeation experiment of Artemisia xanthium oil carrier

Placing the abdominal skin of the treated mouse on a Franz vertical diffusion cell, wherein the skin stratum corneum faces to a sample cell, the dermis faces to a receiving cell, and adding the gel of the xanthium oil carrier prepared in the example 4 with the same drug content into the receiving cell by taking 30% ethanol physiological saline as a receiving medium(COTG) and CANGAI Oil Gel (COG) are placed in a sample cell, 8mL of receiving medium is added into a receiving cell, then the receiving cell is placed on a transdermal diffusion cell, constant temperature water bath is maintained at (32.0 +/-0.5) DEG C, and 100 r.min is carried out^-1Stirring at the speed of (1). 3mL samples were taken at 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 10.0, 12.0h, and equivalent amount of fresh receiving medium at the same temperature was timely supplemented, and the cumulative release amount per unit area of eugenol in each group at different time points was calculated by HPLC analysis, and the results are shown in Table 5, and a drug cumulative release curve was plotted (fig. 3).

The results show that the cumulative permeation amount per unit area of the gel of the Artemisia xanthium oil carrier and the gel of the Artemisia xanthium oil carrier at 72 hours are 0.2459 +/-0.0013 and 0.2008 +/-0.0096 mg-cm respectively^-2The difference between the two is significant (P)<0.05)。

TABLE 3 cumulative permeation of eugenol per unit area of drug at different time points (n ═ 3)

Experimental example 2 in vivo transdermal permeation experiment of Artemisia xanthium oil carrier gel SD rat

Taking 12 male SD rats with weight (250 + -20) g, performing depilation treatment on the abdominal part of the rat one day before administration, wherein the depilation area is 20cm². The dehaired SD rats were randomly divided into two groups: COG group (given ordinary xanthium oil gel patch), COTG group prepared in example 4 (given xanthium oil carrier gel patch), 6 per group. The gel transdermal administration dosage is 20 g/kg^-1(corresponding to eugenol 1X 10)³mg·kg^-1) No water was withheld in fasts for 12h before the experiment. After administration, 0.5mL of blood is taken from rat fundus venous plexus at 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 5.0, 7.0, 9.0, 11.0, 24.0 and 36.0h, and centrifuged (6000 r.min)^-1(ii) a 10min), taking the upper plasma, processing, performing sample injection analysis, recording peak areas of eugenol (As) and paeonol (Ai) in a chromatogram, and calculating the content of eugenol in the plasma. The plasma concentration-time curve is plotted with the sampling time as abscissa and the eugenol concentration in plasma as ordinate (fig. 4).

Blood concentration-Time data results (Table 4) show C for COTG, COG group eugenol_max3.5955 + -0.2006 mug.mL respectively^-1、1.4115±0.3936μg·mL^-1Wherein the COTG group is 2.5474 times of the COG group, and the difference between the COTG group and the COG group is significant (P)<0.05); the pharmacokinetic data were analyzed using DAS 3.0 software and the relevant pharmacokinetic parameters were calculated with the results shown in table 5. The results show AUC in the COTG group_0-t、AUC_0-∞Compared with COG group, the total content of the active ingredients is remarkably improved (P)<0.05). Experimental results show that the COTG transdermal delivery can promote transdermal permeation of the artemisia vulgaris oil, compared with COG, the stability of the medicine is improved, the transdermal permeation rate of the medicine is improved, meanwhile, the bioavailability of the artemisia vulgaris oil transdermal delivery is increased, the permeation is promoted by means of pharmaceutics, the medicine is mild and non-irritant in action with skin, good in biocompatibility and capable of being a potential artemisia vulgaris oil transdermal permeation promoting carrier.

Table 4 eugenol content in the plasma of rats of each group at different time points (n ═ 6)

TABLE 5 COG and COTG transdermal drug delivery pharmacokinetic parameters ((

n＝6)

Claims

1. A percutaneous absorption xanthium oil carrier gel is characterized by being prepared from the following components in parts by mass:

15-150 parts of artemisia vulgaris oil transfersome,

5-15 parts of gel matrix,

30-150 parts of normal saline,

10-50 parts of humectant,

3-10 parts of a pH value regulator.

2. The percutaneously absorbable xanthium oil carrier gel according to claim 1, wherein: the gel is one or more of carbomer gel, chitosan gel and cellulose gel, and the mixing ratio of the gel to the chitosan gel is arbitrary; the humectant is one or more of glycerol, propylene glycol, betaine and hyaluronic acid, and the mixing ratio of the components is arbitrary; the pH value regulator is one or two of triethanolamine and sodium hydroxide, and the mixing ratio of the triethanolamine and the sodium hydroxide is any combination.

3. The percutaneously absorbable xanthium oil carrier gel according to claim 1, which is prepared by the following process steps:

1) preparing the following components in parts by mass:

15-150 parts of artemisia vulgaris oil transfersome,

5-15 parts of gel matrix,

30-150 parts of normal saline,

10-50 parts of humectant,

3-10 parts of a pH value regulator;

4. The percutaneously absorbable xanthium oil carrier gel according to claim 1, wherein: the xanthium oil transfersome is prepared from the following components in parts by mass:

10-40 parts of artemisia vulgaris oil,

1-20 parts of film material,

0.2 to 40 parts of a film softener,

50-150 parts of deionized water.

5. The percutaneously absorbable xanthium oil carrier gel according to claim 1, wherein: the membrane material is one or a combination of more of soybean lecithin, dipalmitoyl phosphatidylcholine and cholesterol, and the combination proportion of the more is optional; the membrane softener is one or a combination of more of sodium cholate, sodium deoxycholate, propylene glycol, ethanol, tween and span, and the combination proportion of the more is arbitrary.

6. The percutaneously absorbable xanthium oil carrier gel according to claim 1, wherein: the xanthium oil carrier is prepared by the following method:

a1, adding a film material into petroleum ether according to the mass/volume ratio of the film material to the petroleum ether = 1: 10-30 to completely dissolve the film material, so as to obtain a petroleum ether solution;

a4, adding the xanthium oil into an aqueous solution of a membrane softener according to the mass ratio of the xanthium oil to the aqueous solution of the membrane softener = 1: 10-30, and carrying out ultrasonic treatment in an ultrasonic processor, wherein the ultrasonic power is 60-120W, and the ultrasonic treatment time is 2-6 min, so as to obtain a xanthium oil suspension;

a5, adding the xanthium oil suspension obtained in the step A4 into a container for preparing the film obtained in the step A2 according to the mass ratio of the film to the xanthium oil suspension = 1: 20-40, and carrying out hydration washing on the film for 1-3 hours under the water bath condition of 30-50 ℃ to obtain the xanthium oil carrier suspension;