Coenzyme Q10 anti-inflammatory analgesic gel and preparation method thereof

Abstract

The application belongs to the technical field of biological medicine manufacturing, and particularly relates to a coenzyme Q10 anti-inflammatory analgesic gel and a preparation method thereof. The application takes coenzyme Q10 as a pharmaceutical active API, adds specific cationic lipids and high-molecular polymer carriers to the excipients by optimizing and screening the prescription, the amount of the excipients, and the like, so that the uniformity and stability of the gel are improved, the skin penetration is significantly improved, and a synergistic effect is achieved in terms of anti-inflammatory analgesia. The combination process of 'oil phase dissolution, emulsification dispersion, and high-pressure homogenization' is adopted to solve the problems of low water solubility and uneven distribution of coenzyme Q10, and ensure the uniform distribution of active ingredients, which has important significance for promoting the clinical application of external anti-inflammatory analgesic preparations.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biological medicine manufacturing, and particularly relates to a coenzyme Q10 anti-inflammatory analgesic gel and a preparation method thereof. BACKGROUND

[0002] Inflammation and pain are common symptoms that are inseparable in clinical and daily scenarios, and are widely seen in various situations such as trauma and edema, muscle strain, arthritis, postoperative recovery, and skin inflammation. They not only bring direct physical discomfort to patients, but also affect the limb function and quality of life. Topical anti-inflammatory analgesic preparations have become one of the preferred ways to relieve such symptoms because they can directly act on the local lesion, avoid gastrointestinal irritation and other systemic side effects caused by oral drugs, and are convenient and effective. The market demand is continuously strong.

[0003] Coenzyme Q10 is a naturally occurring fat-soluble antioxidant in human cells. In recent years, its application value in the field of anti-inflammatory analgesics has been widely explored. It can not only reduce oxidative stress damage at the inflammation site by scavenging excess free radicals and inhibiting lipid peroxidation, but also regulate the release of inflammatory factors (such as TNF-α and IL-6) and block the cascade conduction of inflammatory response. It can also improve the energy metabolism of local tissues and relieve pain signals from the root, with the synergistic effects of anti-inflammatory, antioxidant, and analgesic. Compared with traditional active ingredients such as non-steroidal anti-inflammatory drugs and local anesthetics, coenzyme Q10 has unique advantages such as good biocompatibility, small side effects, and wide application to people, and has become one of the ideal active ingredients for topical anti-inflammatory analgesic preparations.

[0004] There are still many technical bottlenecks to be solved in the existing coenzyme Q10-based external use gel products and related technologies, which seriously limit their clinical application effect and market promotion. First, coenzyme Q10 has strong fat solubility and poor water solubility. Traditional gel matrix is mostly water-soluble or hydrophilic system, which makes it difficult for coenzyme Q10 to disperse uniformly in the matrix, and easy to form agglomeration and precipitation, affecting the appearance uniformity and stability of the gel, and unable to guarantee the effective release of active ingredients. Second, the stratum corneum is a natural physical barrier, and the penetration resistance of the liposoluble component is relatively large. The traditional gel lacks an effective penetration mechanism, so that the dispersed coenzyme Q10 can only stay in the epidermis and is difficult to penetrate the stratum corneum to reach the dermis and subcutaneous inflammatory pain target tissue, resulting in weak anti-inflammatory and analgesic effect, and repeated and large amount of application is required to achieve the expected effect, which reduces the convenience of use and may cause skin stickiness, pore blockage and other discomfort due to local component accumulation. Third, in order to improve the penetration, some existing technologies blindly add a high proportion of penetration enhancer, which can destroy the structure of the stratum corneum and improve the penetration effect to a certain extent, but often accompanied by obvious side effects. On the one hand, organic solvents can easily destroy the balance of hydrophilic and hydrophobic of the gel system, resulting in abnormal rheological properties of the gel, separation of the gel, and reduction of the stability and shelf life of the product. On the other hand, chemical penetration enhancers can stimulate the skin mucosa, especially sensitive skin or damaged skin, which can easily cause redness, itching, stinging and other allergic or irritating reactions, seriously affecting the safety of drug use. In addition, the existing products also have the problems of uneven release rate of active ingredients and short duration of drug effect. Usually, the drug effect decreases significantly 1-2 hours after application, and frequent reapplication is required, which cannot meet the core needs of patients for "rapid onset and long-acting anti-inflammatory analgesia".

[0005] Therefore, in view of the uneven dispersion of coenzyme Q10, poor skin penetration, insufficient drug effect, poor stability, and safety to be improved in the prior art, it has become a technical problem to be solved for those skilled in the art to develop a gel product with reasonable formula and scientific preparation process, which can realize uniform dispersion and efficient transdermal delivery of coenzyme Q10, and has excellent anti-inflammatory and analgesic effect, stability and safety, which is of great significance for promoting the clinical application of external use anti-inflammatory and analgesic preparations. SUMMARY

[0006] Therefore, the purpose of the present application is to overcome the shortcomings of the prior art, and to provide a coenzyme Q10 anti-inflammatory and analgesic gel and a preparation method thereof. By reasonably adding auxiliary materials, the skin penetration, stability and uniformity of the coenzyme Q10 gel are increased, thereby improving the anti-inflammatory and analgesic effect of coenzyme Q10.

[0007] In order to achieve the above-mentioned purpose, the present application provides the following technical solutions:

[0008] The present application provides a coenzyme Q10 anti-inflammatory analgesic gel, which is composed of coenzyme Q10, hydrogel base, humectant, penetration enhancer, high molecular polymer carrier, cationic lipid and surfactant.

[0009] Further, the hydrogel base is selected from one or more of tragacanth, gelatin, xanthan gum, carrageenan, hyaluronic acid, chitosan, alginic acid, gum arabic, carbomer, dextran, cellulose, sodium carboxymethyl cellulose, polyvinyl pyrrolidone, hydroxypropyl methyl cellulose, methyl cellulose and ethyl cellulose.

[0010] More preferably, the hydrogel base is selected from one or more of carrageenan, hyaluronic acid, carbomer and sodium carboxymethyl cellulose.

[0011] Further, the humectant is selected from one or more of glycerol, sorbitol, trehalose, hyaluronic acid, urea, propylene glycol and polyethylene glycol.

[0012] More preferably, the humectant is selected from one or more of glycerol, sorbitol, hyaluronic acid and propylene glycol.

[0013] Further, the penetration enhancer is selected from one or more of peppermint oil, glycerol, azone, turpentine oil, menthol, eucalyptus oil, laurocapram, squalane, benzyl nicotinate, polysorbate, poloxamer and polyoxyethylene castor oil.

[0014] More preferably, the penetration enhancer is selected from one or more of peppermint oil, menthol, laurocapram, poloxamer and polyoxyethylene castor oil.

[0015] Further, the high molecular polymer carrier is selected from at least one of hypromellose, hydroxypropyl methyl cellulose, hypromellose succinate, hypromellose phthalate, acrylic resin, polyvinyl alcohol, polyvinyl pyrrolidone, polyacrylamide, polyacrylamide, polymethyl methacrylate, polyacrylic acid and copovidone.

[0016] More preferably, the high molecular polymer carrier is selected from one or more of hypromellose, hydroxypropyl methyl cellulose, hypromellose succinate, polyvinyl pyrrolidone and polymethyl methacrylate.

[0017] Further, the cationic lipid is selected from one or more of dioleoyltrimethylammonium chloride, hexadecyltrimethylammonium bromide, trimethyl-2,3-dioleyloxypropylammonium chloride, trimethyl-2,3-dioleoyloxypropylammonium bromide, dimethyl-2-(2-aminomethylamino)ethyl-2,3-dioleyloxypropylammonium trifluoroacetate, dimethyl-2-hydroxyethyl-2,3-dioleoyloxypropylammonium bromide, dimethyl-2-hydroxyethyl-2,3-dioleyloxypropylammonium bromide, dimethyl-3-hydroxypropyl-2,3-dioleyloxypropylammonium bromide, dimethyl-4-hydroxybutyl-2,3-dioleyloxypropylammonium bromide, and dimethyl-5-hydroxypentyl-2,3-dioleyloxypropylammonium bromide.

[0018] More preferably, the cationic lipid is selected from one or more of hexadecyltrimethylammonium bromide and trimethyl-2,3-dioleoyloxypropylammonium bromide;

[0019] More preferably, the cationic lipid is a mixture of hexadecyltrimethylammonium bromide and trimethyl-2,3-dioleoyloxypropylammonium bromide in a mass ratio of 1: (2-4).

[0020] Further, the surfactant is selected from one or more of polyethylene glycol 400, polyoxyethylene 40 hydrogenated castor oil, Tween-80, Tween-20, Span-80, caprylocaproyl macrogol glycerides.

[0021] Further, the gel is composed of the following raw materials in parts by weight: coenzyme Q10 2-10 parts, hydrogel matrix 10-20 parts, humectant 2-6 parts, penetration enhancer 0.5-3 parts, high molecular polymer carrier 2-6 parts, cationic lipid 4-8 parts, and surfactant 0.01-0.5 parts.

[0022] Further, the gel further comprises 0.01-0.05 parts of a preservative.

[0023] Further, the preservative is selected from one or more of chlorhexidine acetate, nipagin ethyl, nipagin propyl, nipagin butyl, sodium benzoate, glycerol monostearate, glycerol monolaurate, glycerol monooleate, methyl paraben, propyl paraben, sorbic acid, hydroxyanisole, potassium sorbate, propyl paraben, and benzyl alcohol.

[0024] The present application also provides use of the gel in the preparation of an anti-inflammatory analgesic drug.

[0025] The present application also provides a preparation method of coenzyme Q10 anti-inflammatory analgesic gel, comprising the following steps:

[0026] Step 1, pretreatment: dispersion and dissolution of raw materials

[0027] Take coenzyme Q10, add all penetration enhancers and surfactants, place in a constant temperature water bath at 50-55°C, magnetic stirring for 15-20 min, form a uniform oil phase dispersion, keep warm (avoid low temperature precipitation) for use;

[0028] Take the cationic lipid and add 5 times the mass of purified water, stir at room temperature until completely dissolved, form a cationic water solution, ready for use.

[0029] Step 2, water phase preparation: gel matrix and carrier dissolution

[0030] Take the appropriate amount of purified water and place it in a high-speed dispersion machine, slowly sprinkle the hydrogel matrix and high molecular polymer carrier under low-speed stirring (speed 200-300 r / min), continue stirring for 30 min, then stand for 2 h; Add moisturizing agent to the swollen system, start high-speed stirring (speed 800-1000 r / min) for 10 min, mix evenly, then add the cationic water solution prepared in step 1, continue stirring for 5 min, form a uniform water phase.

[0031] Step 3, emulsion mixing: oil phase and water phase fusion

[0032] Slowly and uniformly add the oil phase dispersion after step 1 to the uniform water phase of step 2, maintain high-speed stirring (speed 1000-1200 r / min) for 20-30 min until the gel viscosity is uniformly increased and there is no particle feeling, form a preliminary emulsion gel system.

[0033] Step 4, homogenization treatment: improve gel fineness and stability

[0034] Transfer the above preliminary gel system to a high-pressure homogenizer, homogenize 2-3 times at a pressure of 20-30 MPa, each cycle for 5 min, break up the possible residual small oil droplets and particles, ensure uniform dispersion of coenzyme Q10 in the gel (particle size controlled at 100-500 nm); The homogenized gel is placed in a vacuum degassing machine at a vacuum degree of -0.06~-0.08 MPa for 15 min to remove air bubbles in the system, and stand at room temperature for 24 h to mature, then the viscosity is stable, and the anti-inflammatory analgesic gel is obtained.

[0035] Compared with the prior art, the present application has the following beneficial effects:

[0036] The application develops an anti-inflammatory analgesic gel taking coenzyme Q10 as a drug API. By optimizing and screening the prescription adjuvant and the amount, adding specific cationic lipids and high molecular polymer carriers to the adjuvant, the uniformity and stability of the gel are improved, the skin penetration is significantly improved, and the synergistic effect in anti-inflammatory analgesia is played. The combination process of "oil phase dissolution, emulsification dispersion and high pressure homogenization" is adopted to solve the problems of low water solubility and uneven dispersion of coenzyme Q10, and to ensure the uniform distribution of active ingredients, which has important significance for promoting the clinical application of external anti-inflammatory analgesic preparations. DETAILED DESCRIPTION

[0037] The following detailed description of the embodiments of the application provided in the examples is not intended to limit the scope of the claimed application, but only represents selected embodiments of the application. Based on the embodiments in the application, all other embodiments obtained by those of ordinary skill in the art without creative labor fall within the scope of the application.

[0038] The experimental methods described in the following examples are all conventional methods unless otherwise specified; the reagents and materials can be obtained by commercial means unless otherwise specified.

[0039] Example 1: An anti-inflammatory analgesic gel of coenzyme Q10

[0040] The components of the anti-inflammatory analgesic gel are shown in the following table:

[0041]

[0042] The preparation process is as follows:

[0043] Step 1, pretreatment: dispersion and dissolution of raw materials

[0044] Take the coenzyme Q10 of the mass fraction in the above table, add all the penetration enhancers and surfactants, place in a 50℃ constant temperature water bath, magnetically stir for 20min, form a uniform oil phase dispersion, and keep warm (avoid low temperature precipitation) for standby;

[0045] Take the cationic lipid and add 5 times the mass of purified water, stir at room temperature until completely dissolved, form a cationic water solution for standby.

[0046] Step 2, water phase preparation: gel matrix and carrier dissolution

[0047] Take the appropriate amount of purified water into the high-speed dispersion machine, low-speed stirring (speed 200 r / min) under slow scattering into the hydrogel matrix and high molecular weight polymer carrier, continue to stir 30 min, then swell 2 h; To the swollen system, open high-speed stirring (speed 1000 r / min) 10 min, mixed evenly after adding the cationic solution prepared in step 1, continue to stir 5 min, form a uniform aqueous phase.

[0048] Step 3, emulsification mixing: oil phase water phase fusion

[0049] The oil phase dispersion solution after step 1 is slowly and uniformly added to the uniform aqueous phase of step 2, and high-speed stirring (speed 1000 r / min) is maintained for 30 min until the gel viscosity is uniformly improved and no particles are felt, forming a preliminary emulsion gel system.

[0050] Step 4, homogenization treatment: improve gel fineness and stability

[0051] The above preliminary gel system is transferred into a high-pressure homogenizer, and is homogenized 2-3 times at 30 MPa pressure, 5 min each cycle, to break the possible residual small oil droplets and particles, and ensure uniform dispersion of coenzyme Q10 in the gel (particle size controlled at 100-200 nm); The homogenized gel is placed in a vacuum defoaming machine, and is defoamed at a vacuum degree of -0.06~-0.08 MPa for 15 min to remove bubbles in the system, and is left to stand at room temperature for 24 h to mature, and the viscosity is stable after 24 h to obtain an anti-inflammatory analgesic gel.

[0052] Example 2 An anti-inflammatory analgesic gel of coenzyme Q10

[0053] The components of the anti-inflammatory analgesic gel are shown in the following table, and the preparation process is the same as that of Example 1.

[0054]

[0055] Example 3 An anti-inflammatory analgesic gel of coenzyme Q10

[0056] The components of the anti-inflammatory analgesic gel are shown in the following table, and the preparation process is the same as that of Example 1.

[0057]

[0058] Example 4 An anti-inflammatory analgesic gel of coenzyme Q10

[0059] The components of the anti-inflammatory analgesic gel are shown in the following table, and the preparation process is the same as that of Example 1.

[0060]

[0061] Comparative Example 1 An anti-inflammatory analgesic gel of coenzyme Q10

[0062] The components of the anti-inflammatory analgesic gel are shown in the following table, and the preparation process is the same as that of Example 1. Compared with Example 1, the mass fraction of each component is different.

[0063]

[0064] Comparative Example 2: An anti-inflammatory analgesic gel of coenzyme Q10

[0065] The components of the anti-inflammatory analgesic gel are shown in the following table, and the preparation process is the same as that of Example 1. Compared with Example 1, no high molecular polymer carrier is added, and the amount of cationic lipid is increased.

[0066]

[0067] Comparative Example 3: An anti-inflammatory analgesic gel of coenzyme Q10

[0068] The components of the anti-inflammatory analgesic gel are shown in the following table, and the preparation process is the same as that of Example 1. Compared with Example 1, no cationic lipid is added, and the amount of high molecular polymer carrier is increased.

[0069]

[0070] Comparative Example 4: An anti-inflammatory analgesic gel of coenzyme Q10

[0071] The components of the anti-inflammatory analgesic gel are shown in the following table, and the preparation process is the same as that of Example 1. Compared with Example 1, the mass ratio of each component of the cationic lipid is 1:5.

[0072] Comparative Example 5: An anti-inflammatory analgesic gel of coenzyme Q10

[0073] The components of the anti-inflammatory analgesic gel are shown in the following table, and the preparation process is the same as that of Example 1. Compared with Example 1, the cationic lipid contains only cetyltrimethylammonium bromide.

[0074]

[0075] Comparative Example 6: An anti-inflammatory analgesic gel of coenzyme Q10

[0076] The components of the anti-inflammatory analgesic gel are shown in the following table, and the preparation process is the same as that of Example 1. Compared with Example 1, in the cationic lipid, dimethyl-2-hydroxyethyl-2,3-dioleoyloxypropylammonium bromide is used instead of trimethyl-2,3-dioleoyloxypropylammonium bromide.

[0077]

[0078] Effect Example 1: Gel content uniformity test

[0079] The gel uniformity of the gels of Examples 1-4 and Comparative Examples 1-6 was determined according to the 2025 edition of the Chinese Pharmacopoeia four-part content uniformity test method (General Rule 0941).

[0080] Ten samples were taken from each group, and the relative content xi of each single dose at the marked amount of 100 was determined, and the average value thereof was calculated and the standard deviation and the absolute value of the difference between the marked amount and the average value .

[0081] If A+2.2S≤L, the content uniformity of the sample meets the requirements; if A+S>L, it does not meet the requirements; if A+2.2S>L and A+S≤L, 20 more samples should be taken for retesting.

[0082] According to the initial and retesting results, the average value , the standard deviation S and the absolute value of the difference between the marked amount and the average value A of 30 single doses were calculated. Then, the following formula was used for calculation and determination.

[0083] When A≤0.25L, if A 2 +S 2 ≤0.25L 2 , the content uniformity of the sample meets the requirements; if A 2 +S 2 >0.25L 2 , it does not meet the requirements. When A>0.25L, if A+1.7S≤L, the content uniformity of the sample meets the requirements; if A+1.7S>L, it does not meet the requirements. In the above formula, L is a specified value, and L=15.0.

[0084] Referring to the above method, the content uniformity of the gels prepared in Examples 1-4 and Comparative Examples 1-6 was determined, and the results are shown in Table 1.

[0085] Table 1 Content uniformity

[0086]

[0087] As can be seen from Table 1 above, the content uniformity of the coenzyme Q10 anti-inflammatory analgesic gels provided by the application is less than 10, which meets the requirements of the pharmacopoeia and is much smaller than that of Comparative Examples 1-6. The gels prepared in the examples have good content uniformity, and the composition and content of the high molecular polymer carrier and the cationic lipid have a greater impact on the content uniformity of the final gel.

[0088] Effect Example 2: Gel stability test

[0089] The test samples (gels prepared in Examples 1-4 and Comparative Examples 1-6) were subjected to an accelerated test at a temperature of 30°C ± 2°C and a relative humidity of 65% ± 5% for 6 months, and the related substances (total impurities, %) were determined, and the results are shown in Table 2:

[0090] Table 2 Stability test results

[0091]

[0092] As shown in Table 2, the gels of Examples 1-4 had little change in related substances (compared with 0 days) after the 6-month accelerated test, indicating high long-term stability. The related substances of Comparative Examples 1-6 were significantly higher than those of the present application after 3 months, indicating that the composition and content of the excipients, such as the high molecular weight polymer carrier and the cationic lipid, have a great influence on the stability of the gel, and the composition of the excipients plays a crucial role in the stability of the entire drug system.

[0093] Example 3: Transdermal gel test

[0094] Sixty SPF rats, half male and half female, weighing 220 ± 20 g, were randomly divided into 10 groups of 6 each, with animal production license number SCXK (Ji)-2020-0002. The SPF rats were maintained on feed provided by Changchun Yis Experimental Animal Technology Co., Ltd. The rats were depilated on the abdomen with 80 g / L sodium sulfide solution, washed with physiological saline, and naturally fed for 24 h. The next day, they were anesthetized with 10% chloral hydrate and then sacrificed, the abdominal skin was immediately peeled off and the subcutaneous fat and tissue were separated, and the undamaged ones were soaked in physiological saline and refrigerated for 12 h before use.

[0095] The rat skin was placed in a Franz diffusion cell (effective permeation area of 3 cm 2 , thickness of about 600 μm), with the stratum corneum facing the supply chamber and the dermis facing the receiving cell. The receiving liquid was 30 mL of methanol / physiological saline (1:1), and the constant temperature water bath was set at 37 ± 1°C with a magnetic stirrer at a speed of 100 rpm. The gels prepared in Examples 1-4 and Comparative Examples 1-6 were reconstituted with methanol / chloroform (V / V = 1:1) to prepare a solution containing 2 mg of coenzyme Q10, which was uniformly coated on the surface of the stratum corneum. After 24 h of administration, 1 mL of sample was taken from the receiving cell (while 1 mL of the same temperature receiving liquid was added), filtered with a 0.22 μm microporous filter, and the concentration of coenzyme Q10 was determined by high performance liquid chromatography. The cumulative transdermal amount was calculated, and the results are shown in Table 3.

[0096] HPLC method analysis using a C18 column, mobile phase methanol: anhydrous ethanol = 70:30 (v / v), flow rate 1.0 mL / min, detection wavelength 275 nm; column temperature 30°C; injection volume 10 μL.

[0097]

[0098] Q = Q0(1-e-kt) n is the cumulative release of a component per unit area (μg / cm2) of the nth sampling, 2 Cn is the concentration of a component in the receiving liquid of the nth sampling (μg / mL), n Cn is the concentration of a component in the receiving liquid of the nth sampling (μg / mL), i Ci (i < n-1) is the mass concentration of coenzyme Q10 in the receiving liquid of the ith sampling (μg / mL), V is the volume of the receiving chamber (30 mL), V0 is the sampling volume (1 mL), and S is the effective permeation area (cm2) during drug diffusion. 2

[0099] Table 3 In vitro transdermal effect of gels

[0100]

[0101] Note: Compared with Example 1, *P < 0.05, **P < 0.01.

[0102] As can be seen from the transdermal effect data in Table 3, the transdermal amount of coenzyme Q10 of Comparative Examples 1-6 gels is significantly lower than that of Examples 1-4, indicating that the cationic lipid and high molecular polymer carrier of the present application can significantly synergistically improve the transdermal effect of active drug API, and can achieve the purpose of promoting the transdermal absorption of coenzyme Q10, which is conducive to the accumulation of gel drugs in the epidermis and dermis.

[0103] Example 4: Anti-inflammatory and analgesic test evaluation

[0104] (1) Writhing test

[0105] SPF rats were taken, half male and half female, weighing 220±20g, and randomly divided into 12 groups, 5 rats in each group, animal production license number SCXK(Ji)-2020-0002, and the maintenance feed of SPF rats was provided by Changchun Yis Experimental Animal Technology Co., Ltd. The 12 groups included a blank control group, a model control group, and Examples 1-4 and Comparative Examples 1-6.

[0106] Group treatment:

[0107] ​Blank control group: no treatment, observe the number of writhing of rats within 10 minutes and record the average value; model control group: no treatment, intraperitoneal injection with 0.6% acetic acid solution (20 mL / kg), observe the number of writhing of mice within 10 minutes, and record the average value of the number of writhing; Example 1-4 and Comparative Example 1-6 groups: after fixing the limbs of mice on the flat plate and shaving the abdomen, the area of shaving is 2x2 cm, 5 mg of gel is applied on the abdomen of mice, continuous administration for 7 days, once a day, 1 hour after the last administration, intraperitoneal injection with 0.6% acetic acid solution (20 mL / kg); observe the number of writhing of mice within 10 minutes, and record the average value of the number of writhing. Compare the difference of the number of writhing of each group for statistical analysis.

[0108] (2) Swelling experiment

[0109] Take 55 SPF rats, half male and half female, divide the 5 rats in the test group into 11 groups at random, and the 12 groups include blank control group, Example 1-4 and Comparative Example 1-6 groups, respectively, shave the abdomen of rats with depilatory cream, the area is 2 cm x 2 cm. First, measure the circumference of the right hind foot of rats, then apply 5 mg of anti-inflammatory analgesic gel of Example 1-4 and Comparative Example 1-6 or the same amount of saline of the blank control group on the abdomen of rats, then fix the rats on the wooden plate to prevent them from scratching off the medicine. 30 minutes after administration, inject 0.1 wt% carrageenan 0.1 mL subcutaneously into the right hind foot of rats, 1 hour after inflammation, measure the circumference of the right hind foot of rats, and take the difference between before and after inflammation as the average swelling degree. Compare the difference of the swelling degree of each group for statistical analysis.

[0110] Table 4 Evaluation of anti-inflammatory analgesic experiment of gel

[0111]

[0112] Note: compared with the blank control group, *P<0.05, **P<0.01; compared with the model control group, #P<0.05, ##P<0.01.

[0113] From the anti-inflammatory analgesic test evaluation results in Table 4, the model control group and the example groups, the comparative example groups and the blank control group are significantly (p<0.01) higher than the number of writhing times of the blank control group, which shows that the intraperitoneal injection of 0.6% acetic acid solution can successfully induce the pain response of the rats, and the model is successfully constructed. However, the number of writhing times of the example groups 1-4 is significantly lower than that of the comparative example groups 1-6, which shows that the gels of the example groups 1-4 can more obviously reduce the pain response of the rats and have a significant analgesic effect in the case of having better permeability. In addition, according to the swelling degree data, the gels of the example groups 1-4 can significantly reduce the swelling effect of the right hind foot of the rats in a short time, which shows that the gels of the present application have a significant anti-inflammatory effect. In summary, the gels prepared by the specific adjuvant components of the example groups 1-4 have the effect of anti-inflammatory analgesia, and the cationic lipids and the high molecular polymer carriers can significantly synergistically improve the transdermal effect of the active drug API, and then play a synergistic effect in the aspect of anti-inflammatory analgesia.

[0114] Based on the above description, those skilled in the art will understand that the present disclosure can be implemented in different specific forms without changing the technical spirit and essential characteristics thereof. Therefore, it should be understood that the above embodiments are not limiting in all aspects, but are illustrative. The scope of the present disclosure is limited by the appended claims, not by the description before them, and therefore all changes and modifications falling within the boundaries and scope of the claims, or the equivalents of such boundaries and scope, are intended to be covered by the claims.

Claims

1. A coenzyme Q10 anti-inflammatory analgesic gel, characterized in that, The coenzyme Q10 2-10 parts, hydrogel matrix 10-20 parts, humectant 2-6 parts, penetration enhancer 0.5-3 parts, high molecular polymer carrier 2-6 parts, cationic lipid 4-8 parts and surfactant 0.01-0.5 parts by weight; wherein, The high molecular polymer carrier is selected from one or more of hydroxyethyl methyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl methyl cellulose succinate and polyvinyl pyrrolidone; The cationic lipid is mixed from cetyl trimethyl ammonium bromide and trimethyl-2,3-dioleoyl bromide propyl ammonium according to a mass ratio of 1: (2-4) ; The hydrogel matrix is selected from one or more of carrageenan, hyaluronic acid, carbomer and sodium carboxymethyl cellulose; The humectant is selected from one or more of glycerol, sorbitol, hyaluronic acid and propylene glycol; The penetration enhancer is selected from one or more of peppermint oil, menthol, laurazepam and polyoxyethylene castor oil; The surfactant is selected from one or more of polyethylene glycol 400, Tween-80, Span-80, caprylic acid capric acid polyethylene glycol glycerol ester.

2. Use of the gel of claim 1 in the preparation of an anti-inflammatory analgesic drug.

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