CN113018254A - Ibuprofen liquid crystal gel transdermal preparation for treating primary dysmenorrhea and preparation method thereof - Google Patents
Ibuprofen liquid crystal gel transdermal preparation for treating primary dysmenorrhea and preparation method thereof Download PDFInfo
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Abstract
An ibuprofen liquid crystal gel transdermal preparation for treating primary dysmenorrhea and a preparation method thereof, belonging to the technical field of primary dysmenorrhea treatment drugs. The hexagonal liquid crystal gel is prepared by emulsifying a water phase and an oil phase, wherein the water phase is prepared from purified water and a bacteriostatic agent, and the oil phase is prepared from a mixed melt of an ibuprofen dissolved in a lipid material and a hexagonal phase inducer. The components comprise 0.01-4 mg of ibuprofen, 65-72 mg of lipid material, 3-4 mg of hexagonal phase inducer, 0.01-2 mg of bacteriostatic agent and 20-27 mu L of purified water. The invention realizes the local application of the water-insoluble drug ibuprofen, and has the advantages of safety, no stimulation, good biological adhesion, targeting, slow release and the like, thereby reducing the administration frequency, reducing the side effect of the drug, improving the bioavailability of the drug, and enhancing the treatment effect of the ibuprofen on primary dysmenorrhea.
Description
Technical Field
The invention belongs to the technical field of primary dysmenorrhea treatment medicines, and particularly relates to an ibuprofen liquid crystal gel transdermal preparation for treating primary dysmenorrhea and a preparation method thereof.
Background
Dysmenorrhea is a common and frequently encountered disease in gynecology, and refers to menstrual diseases with soreness of waist or other discomforts as the main manifestations of lower abdominal pain and distention before and after menstruation or during menstruation. Severe patients can be accompanied with nausea, vomiting, cold sweat, cold hands and feet and even syncope, the incidence rate of dysmenorrhea of women in China is about 3.1 percent, and serious influence is brought to daily work, study and life. Dysmenorrhea is classified into primary dysmenorrhea and secondary dysmenorrhea according to the existence of pelvic organic disease. The secondary dysmenorrhea has relatively definite etiology, is menstrual abdominal pain caused by pelvic organic diseases, and is often complicated by infertility, endometriosis, adenomyosis and genital tract inflammation. The primary dysmenorrhea is not accompanied with pelvic organic diseases, the incidence rate of the primary dysmenorrhea is 80 percent and the cause is not clear in recent literature, and the primary dysmenorrhea is generally accepted to be mainly related to the increase of endometrial Prostaglandin (PG) at present. PGE2 can inhibit spontaneous activity of uterine smooth muscle, and PGF2 alpha promotes uterine smooth muscle contraction to cause uterine smooth muscle spasmodic contraction to cause uterine ischemia and hypoxia, so that acid metabolite is accumulated in muscle layer to cause dysmenorrhea. Meanwhile, PGF2 alpha can also improve the sensitivity of peripheral nerves to pain, and cause dysmenorrhea.
Ibuprofen is the most commonly used drug for treating primary dysmenorrhea, and the drug mainly reduces PGs synthesis by inhibiting Cyclooxygenase (COX), so as to relieve uterine spastic contraction, and is usually taken 1-2 days before menstruation until dysmenorrhea disappears. But ibuprofen is almost insoluble in water, ibuprofen is available in various dosage forms at present, wherein oral preparations are more, the first-pass effect exists, the gastrointestinal tract is stimulated greatly, and the general tablet is easy to cause the phenomenon of blood concentration peak valley. In addition, ibuprofen has a short half-life and requires frequent dosing of large amounts of the drug in order to maintain effective therapeutic concentrations, which limits the clinical use of ibuprofen. Therefore, there is a need to develop new dosage forms for drug delivery that overcome the problem of poor solubility of ibuprofen during oral absorption to improve the bioavailability of ibuprofen.
Transdermal drug delivery systems are drug delivery routes that enter the blood circulation through skin absorption or directly reach the treatment site to achieve disease treatment or prevention, and have received much attention in recent years. The medicine is prepared into a transdermal administration preparation, so that the first pass effect of the liver can be effectively avoided, the side effect of an oral preparation is overcome, and the compliance of patients is increased. Therefore, in order to bring convenience to patients and better exert drug effects, the ibuprofen liquid crystal gel transdermal preparation for treating primary dysmenorrhea is prepared by using a lipid material and a hexagonal phase inducer as matrixes, and the same report is not found at present.
Disclosure of Invention
The technical problem to be solved by the invention is to provide a new administration mode for treating primary dysmenorrhea by using an ibuprofen liquid crystal gel transdermal preparation, so that the administration of patients is more convenient. Meanwhile, the invention provides a preparation method of the ibuprofen liquid crystal gel transdermal preparation.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows: an ibuprofen liquid crystal gel transdermal preparation for treating primary dysmenorrhea is prepared by emulsifying a water phase and an oil phase to prepare hexagonal liquid crystal gel, wherein the water phase is prepared from purified water and a bacteriostatic agent, and the oil phase is prepared from ibuprofen dissolved in a mixed melt of a lipid material and a hexagonal inducer.
As an optimal technical scheme, the ibuprofen liquid crystal gel transdermal preparation contains 0.01-4 mg of ibuprofen, 65-72 mg of lipid material, 3-4 mg of hexagonal phase inducer, 0.01-2 mg of bacteriostatic agent and 20-27 mu L of purified water.
As a further preferable technical scheme, the ibuprofen liquid crystal gel transdermal preparation comprises 4mg of ibuprofen, 71.15mg of lipid material, 3.85mg of hexagonal phase inducer, 2mg of bacteriostatic agent and 25 mu L of purified water.
Preferably, the lipid material (drug-loaded matrix) is one or more of Phytantriol (PHYT), Glycerol Monooleate (GMO), Monoglyceride (MO) and Sorbitol Monooleate (SMO).
As a preferable technical scheme, the hexagonal phase inducer adopts one or two of Tricaprylin (TAG), vitamin E acetate (VitE A) and Paraffin Oil (PO).
As a preferable technical scheme, the bacteriostatic agent adopts one or two of benzoic acid (BEN), methyl paraben (M4HB) and Sodium Methyl Paraben (SMP).
A method for preparing ibuprofen liquid crystal gel transdermal preparation for treating primary dysmenorrhea comprises the following steps:
(1) precisely weighing lipid materials, adding a hexagonal phase inducer, heating in a water bath at the corresponding melting temperature of the lipid materials, adding ibuprofen after the lipid materials and the hexagonal phase inducer are completely mixed and melted, continuing to heat until the ibuprofen is dissolved, and finally, fully mixing by vortex oscillation to serve as an oil phase;
(2) precisely weighing the bacteriostatic agent, dissolving in purified water, and heating in water bath at the same temperature as the oil phase to obtain water phase;
(3) and adding the water phase into the oil phase at the same melting temperature, immediately carrying out vortex oscillation and uniform mixing, and standing and balancing the obtained preparation at room temperature for 2-3 days to obtain the ibuprofen liquid crystal gel transdermal preparation.
Compared with the prior art, the invention has the beneficial effects that:
(1) the novel ibuprofen liquid crystal gel transdermal preparation has a good slow release effect, the administration frequency is reduced, and the side effect of ibuprofen is reduced.
(2) The liquid crystal gel has a microstructure similar to that of a biological membrane, has good biocompatibility, and can enhance drug permeation and improve drug bioavailability.
(3) The gel lipid material and the hexagonal phase inducer adopted by the ibuprofen liquid crystal gel transdermal preparation have the characteristics of safety, no toxicity and good biocompatibility, so that the transdermal preparation has the advantages of high comfort, safety and no stimulation.
(4) The ibuprofen liquid crystal gel transdermal preparation has the advantages of simple preparation process and high long-term stability.
Drawings
Fig. 1 is a photograph of the appearance of a liquid crystal gel prepared from ibuprofen.
Fig. 2 is a polarization microscope photograph of the preparation of ibuprofen liquid crystal gel.
Figure 3 is a small angle X-ray scattering curve for the preparation of ibuprofen liquid crystal gel.
FIG. 4 is a differential scanning calorimetry trace for the preparation of a liquid crystalline gel of ibuprofen; wherein A is tricaprylin; b is phytantriol; c is ibuprofen; d is a physical mixture; e is a blank liquid crystal gel; f is medicine carrying liquid crystal gel.
Figure 5 is an in vitro release profile of ibuprofen liquid crystal gel with carbomer gel.
Fig. 6 is a graph of the mean plasma concentration versus time after the ibuprofen lc gel and carbomer gel were applied to the abdomen.
Fig. 7 is a tissue distribution graph of ibuprofen liquid crystal gel (a) and carbomer gel (b) after abdominal administration.
Detailed Description
The invention is further described in detail below with reference to the figures and examples.
Example 1
The ibuprofen liquid crystal gel transdermal preparation comprises the preparation components of 4mg of ibuprofen, 71.15mg of lipid material, 3.85mg of hexagonal phase inducer, 2mg of bacteriostatic agent and 25 mu L of purified water. The preparation steps are as follows:
(1) 71.15mg of phytantriol and 3.85mg of tricaprylin are precisely weighed and heated in a water bath at 65 ℃ to be in a molten state. Accurately weighing 4mg ibuprofen, dissolving the ibuprofen into a completely molten mixed melt of phytantriol and tricaprylin, and performing vortex oscillation until the ibuprofen and the tricaprylin are fully mixed to serve as an oil phase for later use.
(2) 2mg of sodium methyl paraben was weighed precisely and dissolved in 25. mu.L of purified water and heated in a water bath at 65 ℃ as the aqueous phase.
(3) Adding the water phase into the oil phase at 65 ℃, immediately vortex, shake and mix uniformly, and standing and balancing the obtained preparation at room temperature for 72h to obtain the ibuprofen liquid crystal gel transdermal preparation. The photograph as an appearance was shown in FIG. 1 and was colorless and transparent.
Example 2
Polarizing microscope observation of ibuprofen liquid crystal gel
The ibuprofen liquid crystal gel prepared in example 1 was observed by a polarizing microscope. In order to examine the internal morphology of the gel, a proper amount of sample was placed on a glass slide and covered with a cover glass, and then observed at room temperature with a polarizing microscope at a magnification of 100 times, and as a result, as shown in fig. 2, the ibuprofen liquid crystal gel exhibited a sector pattern with clear texture, and was preliminarily judged to be a hexagonal phase liquid crystal structure.
Example 3
Drawing small-angle X-ray scattering curve of ibuprofen liquid crystal gel
The ibuprofen liquid crystal gel prepared in example 1 was observed by small-angle X-ray diffraction. When X-rays irradiate on a sample, scattering X-rays can appear in a small angle range around an incident beam due to an uneven nanoscale electron density area in the sample, and the lattice type can be determined according to a scattering vector ratio corresponding to each scattering peak of the sample. As a result, as shown in fig. 3, the bragg peak relative position scattering vector ratio is √ 1: v. 3: and V4, proving that the ibuprofen liquid crystal gel is in a hexagonal phase liquid crystal structure.
Example 4
Drawing of ibuprofen liquid crystal gel differential scanning calorimetry graph
And (2) carrying out a differential scanning calorimetry experiment on the ibuprofen liquid crystal gel prepared in the embodiment 1, precisely weighing 5-15 mg of the liquid crystal ibuprofen gel prepared in the embodiment 1, placing the sample in a standard 40 mu L aluminum pot, and immediately sealing the sample by using a press. Heating and scanning in an aluminum pot at a scanning speed of 10 ℃/min in a scanning range of 30-200 ℃ in the presence of nitrogen (at a flow rate of 20mL/min), wherein an empty crucible is used as a reference in the experimental process, and the result is shown in FIG. 4, wherein the ibuprofen drug shows a single sharp endothermic peak at 80 ℃, which indicates the crystallization property of the ibuprofen drug. Pure phytantriol and tricaprylin do not have endothermic peaks in the scanning range, and the blank liquid crystal gel generates new peaks at about 108 ℃, and the interaction of the preparation components is presumed to form new phases. The ibuprofen-loaded liquid crystal gel has a single endothermic peak similar to a blank liquid crystal phase, and a drug peak is not detected, so that the drug is supposed to interact with a preparation carrier and be fused into a phase, and the drug exists in the preparation in an amorphous form.
Example 5
In vitro release behavior of ibuprofen liquid crystal gel
The ibuprofen liquid crystal gel prepared in example 1 was subjected to in vitro release test by dynamic dialysis, and before the test, a dialysis bag (cut-off molecular weight of 10-12KDa) of appropriate length was cut and boiled in distilled water for 10min for sterilization. Accurately weighing 40mg ibuprofen liquid crystal gel and carbomer gel, placing into a dialysis bag, tightening two ends of the dialysis bag, immersing into 14mL release medium (pH7.4 PBS buffer), and placing into a constant temperature oscillator with rotation speed of 100rpm and temperature of 37 deg.C. 1mL was sampled at specific time intervals of 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours, respectively, while the same volume of blank release medium was replenished to meet the sink condition. Filtering the sample solution with 0.22 μm microporous membrane, measuring drug content by HPLC, and calculating cumulative release amount (Q) according to formula (1)nμ g/mL) and a cumulative release curve is plotted with the cumulative release percentage (%) as the ordinate and the time (t, h) as the abscissa, and a release equation is fitted. The experiment was performed in parallel with 3 groups.
In the formula (1), CnRepresents the concentration of the drug in the release medium at the nth sampling point; v0The volume of release medium; ciRepresents the drug concentration at the ith (i ═ n-1) sampling point; viIs the sampling volume of the ith sample.
TABLE 1 fitting equation of 3 kinetic equations for ibuprofen in vitro release and cumulative release amount
As shown in Table 1 and FIG. 5, 57.73% of the ibuprofen in the carbomer gel was released already at 0.5h and 67.29% was released by 2h, showing a distinct burst. The liquid crystal gel releases 15.39% of the drug within 2h, the release amount of the drug gradually increases along with the increase of time, and the whole release process is obviously smooth. The relevant results of the fitting of 3 kinetic equations are shown in the table, the release of ibuprofen from the liquid crystal gel is found to accord with the Higuchi equation, and the ibuprofen hexagonal liquid crystal has a certain slow release effect. In addition, the final cumulative release of the lc gel was 78.51% higher than the carbomer gel, indicating that the ability of the lc gel to release ibuprofen over a prolonged period of time is due to the carbomer gel.
Example 6
Mean plasma concentration-time Change of ibuprofen liquid Crystal gel after Abdominal administration
The ibuprofen liquid crystal gel prepared in example 1 was subjected to a mean blood concentration-time change experiment after abdominal administration, female SD rats (body weight 200 + -10 g) were randomly divided into two groups of 36 rats each, ibuprofen carbomer gel was applied to the control rats at a dose of 20 mg/rat after abdominal depilation, ibuprofen liquid crystal gel was applied to the skin of the experimental rats after abdominal depilation, and the rats were fixed with plaster blanks and medical tapes. Collecting orbital venous plexus blood respectively at 0.5, 1, 2, 4, 6, 7, 12, 17 and 24h, measuring drug concentration in blood plasma by high performance liquid chromatography, calculating pharmacokinetic parameters, and evaluating pharmacokinetic characteristics.
TABLE 2 plasma pharmacokinetic parameters of IBU in female rats after a single administration of 20 mg/rat: (
n＝3)
| Parameter(s) | Unit of | Ibuprofen liquid crystal gel | Ibuprofen carbomer gel |
| AUC(0-∞) | mg/L·h | 207.45±41.45 | 118.03±10.01**** |
| MRT(0-∞) | h | 26.60±3.07 | 10.41±0.47 |
| t1/2 | h | 13.80±2.12 | 5.46±0.35 |
| Tmax | h | 12.00±0.00 | 4±0 |
| Cmax | mg/L | 7.87±0.74 | 12.18±0.67 |
****P<0.0001, compared with ibuprofen gel, has significant difference
The results are shown in Table 2 and FIG. 6, which shows the AUC of the liquid crystal gel(0-∞)Is obviously larger than carbomer gel (P)<0.0001), the IBU in the liquid crystal gel enters the blood more than the carbomer gel after long-time percutaneous administration, and the systemic curative effect of the liquid crystal gel is better than that of the carbomer gel. MRT of liquid crystal gel(0-∞)It is larger than carbomer gel, and in addition, according to the figure, after the abdominal administration, the blood concentration of ibuprofen liquid crystal gel gradually rises, and reaches the peak value within 12h, while the ibuprofen carbomer gel can detect the peak value rapidly (Tmax is 4h), and the concentration is reduced after that, and the liquid crystal gel is supposed to have the slow release effect.
Example 7
Ibuprofen liquid crystal gel and carbomer gel are distributed on abdominal region and drug tissue after administration
The ibuprofen liquid crystal gel and carbomer gel prepared in example 1 were administered to the abdomen to perform a drug tissue distribution experiment, SD female rats (weight 200 + -10 g) were randomly divided into two groups of 36 rats each, ibuprofen carbomer gel was applied to the control rats at a dose of 20 mg/rat after the abdomen had been depilated, ibuprofen liquid crystal gel was applied to the skin of the experimental rats after the abdomen had been depilated, and the rats were fixed with plaster blanks and medical tape. 3 rats were sacrificed at 0.5, 1, 2, 4, 6, 7, 12, 17, 24h cervical dislocation, respectively. Meanwhile, about 200mg of uterus, heart, liver, spleen, lung and kidney are cut immediately, washed with cold saline for 3 times, sucked to be dry by filter paper, added with methanol according to the proportion of 1: 10, homogenized, the content of ibuprofen in each tissue is measured by high performance liquid chromatography, and the distribution of the ibuprofen in the body of the medicine is evaluated.
The results are shown in FIG. 7, AUC of uterus in the liquid crystal and carbomer groups after abdominal transdermal drug administration(0-∞)Is far higher than other tissues and has significant difference, and the ibuprofen is supposed to be targetedly distributed in the uterus through the abdominal administration, thereby achieving the purpose of treating dysmenorrhea.
Example 8
Pharmacodynamic study of ibuprofen liquid crystal gel
1. Establishment of rat primary dysmenorrhea model
40 SD female rats (body weight 200 + -10 g) were randomly divided into a blank group, a model group, a positive control group, a carbomer gel group, and a liquid crystal gel group, each group consisting of 10 rats. After adaptive feeding for 1 week, except for injecting normal saline with equal volume into a blank group, rats of each group are injected with estradiol benzoate injection liquid into the abdominal cavity for 10 days, 1 time/d, 0.5 mg/mouse on days 1 and 10 and 0.2 mg/mouse on days 2-9.
2. Mode of administration
Blank group, after injecting estradiol benzoate injection to each administration group from 5 days, corresponding therapeutic drugs are given for 1 time/d. Except for the normal group, 24 hours after the last administration of estradiol benzoate and 1 hour after the administration, 2U of oxytocin is injected into the abdominal cavity of the rat/a blank group which only induces dysmenorrheal is injected into the abdominal cavity of the rat with physiological saline with equal volume. Number of writhing responses in rats: writhing reaction (contraction and indent of abdomen, extension of trunk and hind limb, internal rotation of hip and one side limb) of rats is an index of uterine contraction and dysmenorrhea, and the number of rats with dysmenorrhea and writhing of animals in 30min after injection of oxytocin to each group of rats and the average writhing number are observed and recorded. And calculating the inhibition rate:
the writhing inhibition ratio (%) was (average writhing reaction times in model group-average writhing reaction times in administration group)/average writhing reaction times in model group × 100%
3. Examination results
TABLE 3 influence of groups on Primary dysmenorrhea model rat writhing response: (
n＝8)
| Group of | Number of writhing reactions in rats in 30 minutes | Rate of inhibition of twisting body |
| Blank group | - | - |
| Model set | 7.40±0.59 | - |
| Positive control group | 3.83±0.20**** | 48.20±1.48％ |
| Ibuprofen liquid crystal gel group | 6.00±0.17** | 18.92±4.2％ |
| Ibuprofen carbomer gel group | 4.25±0.21**** | 42.57±1.75％ |
P <0.01, significant differences from the model group, P <0.0001, significant differences from the model group
The influence of each group on the torsion reaction of the dysmenorrhea model rats is shown in table 3, compared with the model groups, the ibuprofen liquid crystal gel can obviously reduce the torsion times of the dysmenorrhea model rats, and the liquid crystal gel group is superior to the carbomer gel group.
Example 9
Skin irritation test of ibuprofen liquid crystal gel on rats
The ibuprofen liquid crystal gel prepared in example 1 was used for skin irritation test. The skin irritation of ibuprofen liquid crystal gel was studied by irritation scoring of rat tissues. Dividing SD female rats (with weight of 200 + -10 g) into three groups, each group containing six rats, cutting off abdominal hair 24h before experiment, applying the test drug on the hair-removed skin, covering with non-irritant blank cataplasm, and fixing with medical bandage, wherein the blank control group is operated by the same method but is not administered. After 24h of administration, the drug was removed, the site of administration was then washed with warm water, and the local skin was visually observed for the presence or absence of erythema, edema, etc. under appropriate lighting conditions, and a skin irritation response score was recorded.
1. The skin erythema and edema are used as indexes to score according to the guiding principle of research technology of drug irritation, anaphylaxis and hemolysis. The stimulation degree of each index is judged to be 0-4 points according to the weight, the stimulation severity degree is increased along with the increase of the score, and the detailed scoring rules and standards are shown in tables 4 and 5. The total score of the index score is less than 0.5 and is divided into a smaller irritation range. The mild stimulation range is 0.6-2.0. 2.1-6.0 is divided into a moderate stimulation range. The stimulation range is 6.1-8.0.
TABLE 4 skin irritation response Scoring rules
TABLE 5 evaluation criteria for skin irritation Strength
| Mean score | Strength of |
| 0-0.5 | Has no irritation |
| 0.6-2.0 | Mild stimulation |
| 2.1-6.0 | Moderate stimulation |
| 6.1-8.0 | Severe stimulation |
2. Skin irritation score results: (
n＝6)
TABLE 6 skin irritation score results for each group
Results in combination with visual observations, no significant damage was observed in the skin of the three groups of rats and the skin irritation score results are shown in table 6. Ibuprofen liquid crystal gel scored less than 0.5 for skin irritation, indicating that the liquid crystal gel had little skin irritation, whereas carbomer gel scored 1.17, with slight skin irritation. Therefore, the ibuprofen liquid crystal gel only generates micro-irritation to rat skin and meets the requirement of skin administration.
Example 10
The ibuprofen liquid crystal gel transdermal preparation comprises the following preparation steps:
(1) 67mg of glycerol monooleate and 3.5mg of vitamin E acetate are precisely weighed and heated in a water bath at 45 ℃ to be in a molten state. Accurately weighing 0.5mg ibuprofen, dissolving in the completely molten mixed melt of the glycerol monooleate and the vitamin E acetate, and performing vortex oscillation until the ibuprofen and the vitamin E acetate are fully and uniformly mixed to serve as an oil phase for later use.
(2) 0.5mg of methylparaben dissolved in 22. mu.L of purified water was weighed out precisely and heated in a water bath at 45 ℃ to obtain an aqueous phase.
(3) Adding the water phase into the oil phase at 45 ℃, immediately vortex, shake and mix uniformly, and standing and balancing the obtained preparation at room temperature for 72h to obtain the ibuprofen hexagonal phase liquid crystal gel transdermal preparation.
Example 11
The ibuprofen liquid crystal gel transdermal preparation comprises the following preparation steps:
(1) 70.5mg of sorbitol monooleate and 3.25mg of paraffin oil were precisely weighed out and left at room temperature. 3.5mg of ibuprofen is precisely weighed and dissolved in a mixture of sorbitol monooleate and paraffin oil, and the mixture is vortexed and oscillated to be fully and uniformly mixed to be used as an oil phase for standby.
(2) 1.5mg of benzoic acid was accurately weighed at room temperature and dissolved in 27. mu.L of purified water as an aqueous phase.
(3) And adding the water phase into the oil phase at room temperature, immediately vortex, oscillate and uniformly mix, and standing and balancing the obtained preparation at room temperature for 72 hours to obtain the ibuprofen hexagonal phase liquid crystal gel transdermal preparation.
The foregoing is merely exemplary and illustrative of the principles of the present invention and various modifications, additions and substitutions of the specific embodiments described herein may be made by those skilled in the art without departing from the principles of the present invention or exceeding the scope of the claims set forth herein.
Claims (8)
1. The ibuprofen liquid crystal gel transdermal preparation for treating primary dysmenorrhea is characterized in that hexagonal liquid crystal gel is prepared by emulsifying a water phase and an oil phase, the water phase is prepared from purified water and a bacteriostatic agent, and the oil phase is prepared by dissolving ibuprofen in a mixed melt of a lipid material and a hexagonal inducer.
2. The ibuprofen liquid crystal gel transdermal preparation according to claim 1, wherein the components comprise 0.01-4 mg ibuprofen, 65-72 mg lipid material, 3-4 mg hexagonal phase inducer, 0.01-2 mg bacteriostatic agent and 20-27 μ L purified water.
3. The ibuprofen liquid crystal gel transdermal preparation according to claim 2, wherein the components comprise 4mg ibuprofen, 71.15mg lipid material, 3.85mg hexagonal phase inducer, 2mg bacteriostatic agent and 25 μ L purified water.
4. The ibuprofen liquid crystal gel transdermal formulation according to claim 1, 2 or 3, wherein said lipid material employs one or more of phytantriol, glyceryl monooleate, monoglyceride and sorbitol monooleate.
5. The ibuprofen liquid crystal gel transdermal preparation according to claim 1, 2 or 3, wherein the hexagonal phase inducer is one or two of tricaprylin, vitamin E acetate and paraffin oil.
6. The ibuprofen liquid crystal gel transdermal preparation according to claim 1, 2 or 3, wherein the bacteriostatic agent is one or two of benzoic acid, methyl paraben and sodium methyl paraben.
7. A method for preparing the ibuprofen liquid crystal gel transdermal preparation of any claim 1 to 6, which comprises the following steps:
(1) precisely weighing lipid materials, adding a hexagonal phase inducer, heating in a water bath at the corresponding melting temperature of the lipid materials, adding ibuprofen after the lipid materials and the hexagonal phase inducer are completely mixed and melted, continuing to heat until the ibuprofen is dissolved, and finally, fully mixing by vortex oscillation to serve as an oil phase;
(2) precisely weighing the bacteriostatic agent, dissolving in purified water, and heating in water bath at the same temperature as the oil phase to obtain water phase;
(3) and adding the water phase into the oil phase at the same melting temperature, immediately carrying out vortex oscillation and uniform mixing, and standing and balancing the obtained preparation at room temperature for 2-3 days to obtain the ibuprofen liquid crystal gel transdermal preparation.
8. The ibuprofen liquid crystal gel transdermal preparation of any one of claims 1 to 6, for use in the treatment of primary dysmenorrhea.
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