Traditional Chinese medicine self-emulsifying ointment, traditional Chinese medicine semi-solid spray and preparation method thereof

Abstract

The invention discloses a traditional Chinese medicine self-emulsifying ointment, which takes water and / or ethanol as a solvent, and comprises 6-26 wt% of a solvent, 1-4 wt% of a traditional Chinese medicine extract and 70-90 wt% of an anhydrous plant-based semi-solid self-emulsifying matrix, and the anhydrous plant-based semi-solid self-emulsifying matrix comprises 30-45 wt% of anhydrous plant-based oil, 10-25 wt% of an emulsifier, 10-25 wt% of a co-emulsifier and 10-25 wt% of a thickener. According to the traditional Chinese medicine self-emulsifying ointment, the traditional Chinese medicine extract has good dispersity in the anhydrous plant-based semi-solid self-emulsifying matrix and does not have obvious crystals, the prepared traditional Chinese medicine self-emulsifying ointment is good in drug release performance, and the particle size is smaller than or equal to 150 microns. The invention further discloses a traditional Chinese medicine semi-solid spray which comprises the traditional Chinese medicine self-emulsifying ointment and a propellant, and the mass ratio of the traditional Chinese medicine self-emulsifying ointment to the propellant is (1-3): 1. The uniform and stable anhydrous semisolid antibiotic spray preparation is obtained by adjusting different proportions of the propellant and the traditional Chinese medicine self-emulsifying ointment.

Description

Technical Field

[0001] The invention relates to the technical field of traditional Chinese medicine and traditional Chinese medicine preparation, and in particular to a traditional Chinese medicine self-emulsifying ointment, a traditional Chinese medicine semi-solid spray and a preparation method thereof. Background Art

[0002] The ancient medical book "Puji Fang" records a traditional Chinese medicine external ointment, which is widely used in the treatment of skin diseases, trauma, inflammation and other diseases. It is mainly composed of Scutellaria baicalensis, Coptis chinensis and Phellodendron chinense; and this Chinese medicine external ointment has a long tradition of application in the history of Chinese medicine, relying on its anti-inflammatory, antibacterial and analgesic effects. Among them, Scutellaria baicalensis contains a variety of flavonoids, which have significant anti-inflammatory, antibacterial and antiviral effects. The main active ingredient of Coptis chinensis is berberine, which is known for its strong antibacterial, anti-inflammatory and antioxidant abilities, and can inhibit skin infections and inflammatory reactions. Phellodendron chinense is rich in phellodendronine and other alkaloids, has a wide range of antibacterial and anti-inflammatory activities, and is often used in the treatment of trauma and skin infections.

[0003] As one of the crystallizations of wisdom in my country for thousands of years, Chinese medicine has a wide range of application potential and universal and precise curative effects. In recent years, Chinese medicine ointments have been used as common preparations in various Chinese medicine departments due to their effects of cooling blood, detoxifying, dispersing blood stasis and purging fire. The Chinese patent document with publication number CN117752709A discloses a Chinese medicine ointment for reducing swelling and relieving pain, which is made of the following raw materials in parts by weight: 42.2-43.0 parts of camphor, 2.0-3.0 parts of Panax notoginseng, 4.0-6.0 parts of safflower, 6.4-7.0 parts of red lead, 4.0-6.0 parts of white oil, 8.6-9.0 parts of calcium carbonate, 4.8-5.2 parts of talc, 4.0-5.0 parts of alum, 4.0-6.0 parts of vegetable oil, 4.0-5.0 parts of borneol and 12.3-13.0 parts of water.

[0004] A Chinese patent document with publication number CN110840986A discloses a Chinese medicine ointment and a preparation method thereof. The Chinese medicine ointment comprises the following components in parts by weight: 254 parts of menthol, 100 parts of camphor, 50 parts of peppermint oil, 50 parts of eucalyptus oil, 30 parts of eugenol, 15 parts of cinnamon oil, 5 parts of patchouli oil, 1 part of spikenard oil, 1 part of dragon's blood, 110-130 parts of shellac wax, 150-153 parts of yellow vaseline, 5 parts of concentrated ammonia solution, 45-55 parts of insect white wax and 161.5-165 parts of stearic acid.

[0005] Although traditional Chinese medicine external treatment can make the drug reach the diseased site directly and the patient has good tolerance. At present, most of the traditional Chinese medicine external ointment preparations still use mineral oil, vaseline and other excipients as dispersants, which will cause inconveniences such as greasy and sticky clothes, and the drug release ability is poor. Therefore, the field urgently needs to develop drug preparations of traditional Chinese medicine extracts, which can not only make the active ingredients of the drug evenly dispersed in the matrix, but also improve the skin experience and enhance the efficacy. Summary of the invention

[0006] In order to solve the above technical problems, the present invention provides a traditional Chinese medicine self-emulsifying ointment, which has good dispersibility and can promote drug release.

[0007] A traditional Chinese medicine self-emulsifying ointment, which uses water and / or ethanol as a solvent and comprises 6-26wt% of a solvent, 1-4wt% of a traditional Chinese medicine extract, and 70-90wt% of an anhydrous plant-based semisolid self-emulsifying matrix; the anhydrous plant-based semisolid self-emulsifying matrix comprises 30-45wt% of anhydrous plant-based oil, 10-25wt% of an emulsifier, 10-25wt% of an auxiliary emulsifier, and 10-25wt% of a thickener.

[0008] Traditional Chinese medicine preparations are mostly made by directly mixing the powdered Chinese medicine with a yellow vaseline matrix, resulting in large particle size. Yellow vaseline is an oily matrix. Due to its greasiness and poor hydrophobicity, the powdered Chinese medicine particles are in a suspended state in the vaseline matrix with poor dispersibility, resulting in poor drug release performance and are not easy to be washed off with water.

[0009] In the present invention, Chinese medicine extract is used instead of Chinese medicine powdered particles as the main active ingredient of Chinese medicine self-emulsifying ointment, anhydrous plant-based semi-solid self-emulsifying matrix is ​​used as the dispersant of Chinese medicine extract, and Chinese medicine extract is evenly mixed in the anhydrous plant-based semi-solid self-emulsifying matrix without obvious stratification, and has good dispersibility. The particle size of the Chinese medicine self-emulsifying ointment of the present invention is ≤150μm, there is no obvious granular feeling when applying, it meets the particle size regulations of the Chinese Pharmacopoeia for ointments, and the drug release performance of the Chinese medicine self-emulsifying ointment is good.

[0010] Preferably, the Chinese herbal medicine extract is an extract of Scutellaria baicalensis, Phellodendron amurense and Coptis chinensis.

[0011] Traditional three yellow (Scutellaria baicalensis, Coptis chinensis and Phellodendron amurense) Chinese medicine preparations are mostly made by directly mixing Chinese medicine powder with vaseline matrix, and the prepared Chinese medicine ointment has no obvious antibacterial activity. In the present invention, flavonoids in Scutellaria baicalensis, berberine in Coptis chinensis, phellodendronine in Phellodendron amurense and the like are extracted, and the extracted Chinese medicine extract has antibacterial activity. The Chinese medicine self-emulsifying ointment obtained by mixing the Chinese medicine extract with anhydrous plant-based semi-solid self-emulsifying matrix has obvious antibacterial effect.

[0012] Further preferably, based on the raw materials used in preparing the traditional Chinese medicine extract, the mass ratio of Scutellaria baicalensis, Phellodendron amurense and Coptidis chinensis is 1:1:1.

[0013] Preferably, the anhydrous plant-based oil is one of oleyl alcohol (OA), isopropyl myristate (IPM), and cocoyl capryloyldecanoate (3C).

[0014] Preferably, the emulsifier is one of polyoxyethylene 40 hydrogenated castor oil (RH40), polyoxyethylene castor oil (ELP), polysorbate 20 (PS20) and polysorbate 80 (PS80).

[0015] Preferably, the co-emulsifier is one of 1,2-propylene glycol (PG), ethoxydiglycol, ethanol, glycerol, polyethylene glycol 400 and polyether L-44.

[0016] Preferably, the thickener is one of glyceryl mono- and distearate II (GMS II), poloxamer 407 (P407), stearyl alcohol and stearic acid.

[0017] Further preferably, the Chinese medicine self-emulsifying ointment comprises 4wt% of extracts of Scutellaria baicalensis, Phellodendron amurense and Coptis chinensis, 16wt% of deionized water, 38wt% of isopropyl myristate, 12wt% of polyoxyethylene castor oil, 18wt% of ethoxydiglycol and 12wt% of glyceryl mono- and distearate II.

[0018] In the present invention, the particle size of the Chinese medicine self-emulsifying ointment composed above is less than 150 μm, and most of the particles are less than 100 μm, indicating that the extracts of Scutellaria baicalensis, Phellodendron chinense and Coptis chinensis are uniformly dispersed in the anhydrous plant-based semisolid self-emulsifying matrix composed above, without obvious large particles, which meets the particle size regulations of the Chinese Pharmacopoeia for ointments, and the viscosity of the Chinese medicine self-emulsifying ointment is low, which is conducive to application. At the same time, the Chinese medicine self-emulsifying ointment composed above has a good antibacterial effect on Staphylococcus aureus, which can solve the problem of increased drug resistance caused by antibiotic-based antibacterial ointments to a certain extent.

[0019] The present invention also provides a method for preparing the above-mentioned traditional Chinese medicine self-emulsifying ointment, which directly and evenly disperses the traditional Chinese medicine extract into the anhydrous plant-based semi-solid self-emulsifying matrix, and the preparation method is simple.

[0020] A method for preparing a traditional Chinese medicine self-emulsifying ointment comprises the following steps:

[0021] (1) crushing Scutellaria baicalensis, Phellodendron amurense and Coptidis chinensis into powder, dispersing the powder in an extraction solvent, heating under reflux, filtering, concentrating and drying to obtain a Chinese medicine extract;

[0022] (2) mixing anhydrous plant-based oil, an emulsifier, a co-emulsifier and a thickener, heating and stirring until uniform, to obtain anhydrous plant-based semisolid self-emulsifying matrix;

[0023] (3) dissolving the Chinese herbal extract obtained in step (1) in a solvent, adding the solvent to the anhydrous plant-based semisolid self-emulsifying matrix obtained in step (2), and stirring evenly to obtain a Chinese herbal self-emulsifying ointment.

[0024] In the present invention, the Chinese medicinal materials are powdered to extract the Chinese medicinal extracts, and the Chinese medicinal extracts are used as active ingredients of the medicine, which can effectively improve its dispersibility and enhance the drug release capacity. The preparation method is simple and easy to operate.

[0025] Preferably, the extraction solvent is water and / or ethanol.

[0026] The present invention also provides a traditional Chinese medicine semi-solid spray, comprising the traditional Chinese medicine self-emulsifying ointment and a propellant, wherein the mass ratio of the traditional Chinese medicine self-emulsifying ointment to the propellant is 1 to 3:1.

[0027] In the present invention, the prepared Chinese medicine self-emulsifying ointment can directly form a stable emulsion with the propellant to avoid the stratification of the emulsion. The present invention obtains a uniform and stable Chinese medicine semi-solid spray by adjusting different ratios of the propellant and the Chinese medicine self-emulsifying ointment.

[0028] At the same time, the present invention adopts a non-contact drug administration method and is applied to the skin surface through aerosol spray technology. The Chinese medicine semi-solid spray formed after mixing can achieve controllable viscosity by adjusting the proportion of thickener in the Chinese medicine self-emulsifying ointment, meet the application of different scenarios, avoid cross infection or secondary injury caused by manual application, and improve patient compliance. The Chinese medicine semi-solid spray is particularly suitable for the treatment of skin inflammation, eczema, trauma and other skin diseases, and has the advantages of easy use, significant efficacy, and easy storage. The Chinese medicine semi-solid spray of the present invention shows a significant inhibitory effect on Staphylococcus aureus, providing a new way for the modernization of traditional Chinese medicine ointments.

[0029] Preferably, the propellant is dimethyl ether (DME), alkane or fluorine-containing alkane.

[0030] Further preferably, in the Chinese medicine semi-solid spray, the Chinese medicine self-emulsifying ointment comprises 4wt% of extracts of Scutellaria baicalensis, Phellodendron chinense and Coptis chinensis, 16wt% deionized water, 38wt% isopropyl myristate, 12wt% polyoxyethylene castor oil, 18wt% ethoxydiglycol and 12wt% glyceryl mono- and distearate II; the mass ratio of the Chinese medicine self-emulsifying ointment to the propellant is 2:1.

[0031] In the present invention, the Chinese medicine self-emulsifying ointment particles of the above components have small particle size and good dispersibility, can directly form a stable low-viscosity emulsion with the propellant, avoid the stratification phenomenon of the emulsion, and the obtained Chinese medicine semi-solid spray preparation is uniform and stable. The low-viscosity emulsion quickly forms a semi-solid film after spraying, has good adhesion, and reduces stickiness and discomfort. At the same time, the prepared Chinese medicine semi-solid spray preparation still retains the antibacterial activity of the Chinese medicine self-emulsifying ointment.

[0032] The present invention also provides a method for preparing the above-mentioned Chinese medicine semi-solid spray, comprising the following steps: directly mixing the Chinese medicine self-emulsifying ointment and the propellant evenly to obtain the Chinese medicine semi-solid spray.

[0033] The preparation method directly adds a propellant into a traditional Chinese medicine self-emulsifying ointment to prepare a stable traditional Chinese medicine semi-solid spray. The preparation method is simple and easy to operate.

[0034] Compared with the prior art, the present invention has the following beneficial effects:

[0035] (1) In the present invention, an anhydrous plant-based semisolid self-emulsifying matrix is ​​used as a dispersant for the Chinese herbal medicine extract. The Chinese herbal medicine extract has good dispersibility in the anhydrous plant-based semisolid self-emulsifying matrix without obvious crystallization. The prepared Chinese herbal medicine self-emulsifying ointment has good drug release performance and a particle size of ≤150 μm, which meets the particle size requirements of the Chinese Pharmacopoeia for ointments.

[0036] (2) In the present invention, the Chinese medicine self-emulsifying ointment can directly form a stable low-viscosity emulsion with the propellant to avoid stratification of the emulsion. By adjusting the different ratios of the propellant and the Chinese medicine self-emulsifying ointment, a uniform and stable Chinese medicine semi-solid spray can be obtained.

[0037] (3) The present invention directly adds a propellant into a traditional Chinese medicine self-emulsifying ointment to prepare a stable traditional Chinese medicine semi-solid spray, and the preparation method is simple and easy to operate. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 The pictures are of the anhydrous plant-based semisolid self-emulsifying matrix prepared in Examples 1 to 5, wherein from left to right are Examples 1 to 5.

[0039] Figure 2 The pictures are of the Chinese medicine self-emulsifying ointments prepared in Examples 1 to 5, wherein from left to right are Examples 1 to 5.

[0040] Figure 3 The pictures are of the Chinese medicine self-emulsifying ointments prepared in Examples 6 and 7, wherein from left to right are Examples 6 and 7.

[0041] Figure 4 These are pictures of the Chinese medicine semi-solid sprays prepared in Examples 8 to 11, wherein from left to right they are Examples 8 to 11, the upper picture is a front view, and the lower picture is a bottom photograph.

[0042] Figure 5 The following are photos of the spraying of the Chinese medicine semi-solid spray prepared in Example 8, wherein the left photo is a photo of the spraying, and the right photo is a photo of the state after the spraying.

[0043] Figure 6The pictures are of the Chinese medicine semi-solid sprays prepared in Examples 12 and 13, wherein from left to right are Examples 12 and 13, the upper picture is a front view, and the lower picture is a bottom photo.

[0044] Figure 7 This is a picture of the Chinese medicine ointment prepared in Comparative Example 2.

[0045] Figure 8 These are pictures of the Chinese medicine semi-solid sprays prepared in Comparative Examples 3 to 5, wherein from left to right they are Comparative Examples 3 to 5, the upper picture is a front view, and the lower picture is a bottom photograph.

[0046] Fig. 9 These are microscopic images of the Chinese medicine self-emulsifying ointments prepared in Examples 1 to 5 and the Chinese medicine ointment prepared in Comparative Example 1, wherein A to F are microscopic images of Examples 1 to 5 and Comparative Example 1, respectively.

[0047] Fig.10 These are microscopic images of the Chinese medicine semi-solid sprays prepared in Examples 8 and 9, wherein A and B are microscopic images of Example 8 at 10 times and 20 times, and C and D are microscopic images of Example 9 at 10 times and 20 times.

[0048] Fig.11 and Fig.12 The viscosity-shear rate change curves and viscosity-temperature change curves of the Chinese medicine self-emulsifying ointments prepared in Examples 1 to 5 and the Chinese medicine ointment prepared in Comparative Example 1 are shown.

[0049] Fig.13 and Fig.14 The viscosity-shear rate change curves and viscosity-temperature change curves of the Chinese medicine semi-solid sprays prepared in Examples 8 to 11 and the Chinese medicine ointment prepared in Comparative Example 1 are shown.

[0050] Fig.15 This is a diagram showing the inhibition zone effect of Chinese herbal medicine extracts on Staphylococcus aureus.

[0051] Fig.16 The figures are the antibacterial circle effect diagrams of the Chinese medicine self-emulsifying ointment prepared in Example 2 and the Chinese medicine semi-solid spray prepared in Examples 8 and 9 on Staphylococcus aureus, wherein A and C are the antibacterial circles of the Chinese medicine self-emulsifying ointment prepared in Example 2 and the Chinese medicine ointment prepared in Comparative Example 1 on Staphylococcus aureus, B and D are the antibacterial circles of the anhydrous plant-based semi-solid self-emulsifying matrix prepared in Example 2 and the yellow vaseline of Comparative Example 1 on Staphylococcus aureus, and E and F are the antibacterial circles of the Chinese medicine semi-solid sprays prepared in Examples 8 and 9 on Staphylococcus aureus. DETAILED DESCRIPTION

[0052] The present invention will be further described in detail below in conjunction with the examples, but the embodiments of the present invention are not limited to the following examples.

[0053] The raw materials used in the present invention are all commercially available.

[0054] Example 1: Preparation of Chinese medicine self-emulsifying ointment

[0055] (1) 16.7 g of Scutellaria baicalensis, 16.7 g of Phellodendron chinense and 16.7 g of Coptis chinensis were crushed into powder using a powder grinder, and the powder was dispersed in deionized water, heated to reflux, and reacted for 6 h, then the residue was removed by suction filtration, the deionized water was removed by vacuum distillation, and the extract was dried in a vacuum drying oven to obtain a Chinese medicine extract;

[0056] (2) 40 wt % of isopropyl myristate (IPM), 10 wt % of polyoxyethylene 40 hydrogenated castor oil (RH40), 18 wt % of 1,2-propylene glycol (PG) and 12 wt % of glyceryl mono- and distearate II (GMS II) were heated and stirred at 60° C. until a uniform phase was obtained to obtain an anhydrous plant-based semisolid self-emulsifying matrix;

[0057] (3) Weigh 1 g of the Chinese herbal extract obtained in step (1), disperse it in 4 mL of deionized water, and stir until uniform to obtain a dispersion of the Chinese herbal extract (i.e., 4 wt% of the Chinese herbal extract and 16 wt% of deionized water). Add the dispersion of the Chinese herbal extract to the anhydrous plant-based semisolid self-emulsifying matrix obtained in step (2), stir until uniform, and obtain a Chinese herbal self-emulsifying ointment.

[0058] Examples 2-5: Preparation of Chinese medicine self-emulsifying ointment

[0059] The preparation method is the same as that of Example 1, with the following differences.

[0060] Table 1: Differences of the preparation methods of Examples 1 to 5

[0061]

[0062] The anhydrous plant-based semisolid self-emulsifying matrix prepared in Examples 1 to 5 is as follows Figure 1 As shown, the Chinese medicine self-emulsifying ointment is Figure 2 As shown, it can be observed that the self-emulsifying ointments prepared in Examples 1 to 5 are all uniform ointments without obvious particle precipitation.

[0063] Examples 6-7: Preparation of Chinese medicine self-emulsifying ointment

[0064] The preparation method is the same as that of Example 1, with the following differences.

[0065] Table 2: Differences between the preparation methods of Examples 6 and 7

[0066]

[0067] The Chinese medicine self-emulsifying ointment prepared in Examples 6 and 7 is as follows Figure 3 As shown, it can be observed that the self-emulsifying ointments prepared in Examples 1 to 5 are all uniform ointments without obvious particle precipitation.

[0068] Example 8: Preparation of Chinese medicine semi-solid spray

[0069] The Chinese medicine self-emulsifying ointment prepared in Example 2 was transferred to a GK-500 pressure-resistant bottle, the bottle mouth was sealed, dimethyl ether (DME) was added to the bottle, wherein the mass ratio of the Chinese medicine self-emulsifying ointment to dimethyl ether was 2:1, and the mixture was shaken to be fully mixed to obtain a Chinese medicine semi-solid spray, such as Figure 4 As shown, no obvious stratification phenomenon was observed and no obvious drug precipitation was observed.

[0070] Figure 5 This is a picture of a Chinese medicine semi-solid spray. As shown in the picture, after spraying onto the surface, the low-boiling-point propellant evaporates quickly, and the self-emulsifying system disperses quickly to form a thin and uniform protective film. This film usually has good adhesion and can solidify into a semi-solid state in a short time, reducing the stickiness and discomfort.

[0071] Example 9: Preparation of Chinese medicine semi-solid spray

[0072] The preparation method is the same as that of Example 8, except that the mass ratio of the Chinese medicine self-emulsifying ointment to dimethyl ether is 3:1. Figure 4 As shown, no obvious stratification phenomenon was observed and no obvious drug precipitation was observed.

[0073] Example 10: Preparation of Chinese medicine semi-solid spray

[0074] The preparation method is the same as that of Example 8, except that the Chinese medicine self-emulsifying ointment used is that prepared in Example 3, and the mass ratio of the Chinese medicine self-emulsifying ointment to dimethyl ether is 2:1. Figure 4 As shown, no obvious stratification phenomenon was observed and no obvious drug precipitation was observed.

[0075] Example 11: Preparation of Chinese medicine semi-solid spray

[0076] The preparation method is the same as that of Example 8, except that the Chinese medicine self-emulsifying ointment used is that prepared in Example 3, and the mass ratio of the Chinese medicine self-emulsifying ointment to dimethyl ether is 3:1. Figure 4 As shown, no obvious stratification phenomenon was observed and no obvious drug precipitation was observed.

[0077] Example 12: Preparation of Chinese medicine semi-solid spray

[0078] The preparation method is the same as that of Example 8, except that the Chinese medicine self-emulsifying ointment used is that prepared in Example 6, and the mass ratio of the Chinese medicine self-emulsifying ointment to dimethyl ether is 2:1. Figure 6 As shown, no obvious stratification phenomenon was observed and no obvious drug precipitation was observed.

[0079] Example 13: Preparation of Chinese medicine semi-solid spray

[0080] The preparation method is the same as that of Example 8, except that the Chinese medicine self-emulsifying ointment used is that prepared in Example 6, and the mass ratio of the Chinese medicine self-emulsifying ointment to dimethyl ether is 3:1. Figure 6 As shown, no obvious stratification phenomenon was observed and no obvious drug precipitation was observed.

[0081] Comparative Example 1

[0082] 50 g of the mixed powder of Scutellaria baicalensis, Phellodendron chinense and Coptidis rhizome of Example 1 was added to 100 g of vaseline and mixed to prepare a traditional Chinese medicine ointment.

[0083] Comparative Example 2

[0084] The preparation method is the same as that of Example 2, except that the anhydrous plant-based oil (isopropyl myristate) is replaced with cetyl palmitate (CP). Figure 6 As shown, compared with anhydrous plant-based oil, CP has poor compatibility with active pharmaceutical ingredients and has obvious stratification phenomenon.

[0085] Comparative Example 3

[0086] The preparation method is the same as that of Example 10, except that the mass ratio of the Chinese medicine self-emulsifying ointment to dimethyl ether is 2:3. Figure 8 As shown in the left figure, obvious stratification was observed and there were obvious particles at the bottom that were not completely dissolved.

[0087] Comparative Example 4

[0088] The preparation method is the same as that of Comparative Example 3, except that the Chinese medicine self-emulsifying ointment used is prepared in Example 4, and the mass ratio of the Chinese medicine self-emulsifying ointment to dimethyl ether is 2:3. Figure 8 As shown in the middle figure, obvious stratification was observed and there were obvious particles at the bottom that were not completely dissolved.

[0089] Comparative Example 5

[0090] The preparation method is the same as that of Comparative Example 3, except that the Chinese medicine self-emulsifying ointment used is prepared in Example 5, and the mass ratio of the Chinese medicine self-emulsifying ointment to dimethyl ether is 2:3. Figure 8 As shown in the right figure, obvious stratification was observed and there were obvious particles at the bottom that were not completely dissolved.

[0091] Sample analysis

[0092] 1. Dispersion Evaluation

[0093] The Chinese medicine self-emulsifying ointments prepared in Examples 1 to 5 and the Chinese medicine semi-solid spray samples prepared in Examples 8 and 9 were observed using an optical microscope.

[0094] Specifically, a small amount of the above sample was taken, placed on a glass slide, gently covered with a coverslip, and then placed under a microscope. An optical microscope was used to observe the sample using a 10x or 20x objective lens, and photos were collected and the particle size was analyzed using Image J software.

[0095] Fig. 9 The microscopic images of the Chinese medicine self-emulsifying ointment prepared in Examples 1 to 5 and the Chinese medicine ointment prepared in Comparative Example 1 under a 10x objective lens are shown, wherein A to F are respectively microscopic images of Examples 1 to 5 and Comparative Example 1. As shown in the figure, the particle size of the Chinese medicine self-emulsifying ointment prepared in Examples 1 to 5 is less than 150 μm, and most of the particle size is less than 100 μm, while the particle size of the Chinese medicine ointment prepared in Comparative Example 1 varies greatly, and there are particles with a particle size greater than 180 μm, which does not meet the Chinese Pharmacopoeia's regulations on the particle size of ointments, indicating that the active ingredients of the Chinese medicine (Scutellaria baicalensis, Phellodendron chinense and Coptis chinensis) are not evenly distributed in the ointment preparation, and the Chinese medicine ointment prepared in Comparative Example 1 is slightly rough during application due to its large particles, and the granularity can be clearly felt, making it difficult to be evenly applied on the skin, thereby affecting the comfort of use and reducing the patient's compliance.

[0096] Fig.10 The figures are microscopic images of the Chinese medicine semi-solid sprays prepared in Examples 8 and 9 under 10x and 20x objective lenses, wherein A and B are microscopic images of Example 8, and C and D are microscopic images of Example 9. As shown in the figure, the Chinese medicine semi-solid sprays prepared in Examples 8 and 9 have no large-particle drug particle distribution, indicating that the Chinese medicine extract prepared in the self-emulsifying system is uniformly distributed in the matrix.

[0097] Therefore, the Chinese medicine semi-solid spray of the present invention can achieve good dispersion of the Chinese medicine extract, and the dispersibility of both the Chinese medicine self-emulsifying ointment and the Chinese medicine semi-solid spray is better than that of the traditional ointment.

[0098] 2. Viscosity evaluation

[0099] The changes of "viscosity with shear rate" and "viscosity with temperature" of the Chinese medicine self-emulsifying ointments prepared in Examples 1 to 5 and the Chinese medicine semi-solid spray samples prepared in Examples 8 to 11 were tested using a rotational rheometer.

[0100] Specifically, a small amount of the above sample (the spray preparation was sprayed in advance and transferred to the rheometer) was transferred to a 20 mm 0° plate, and the flow ramp mode was used, the gap value was 500 μm, the temperature was 25°C, and the shear rate was set to 0.1-100 s. -1 , the "viscosity-shear rate" curve was obtained by testing; a small amount of the above sample was taken and placed on a 20 mm 0° flat plate, using the Flow-rampTemperature mode, with a gap value of 500 μm and a shear rate of 1.25 s -1 , the temperature change is set to 20-50°C, and the test obtains the "viscosity-temperature" change curve.

[0101] Fig.11 and Fig.12 The viscosity-shear rate change curves and viscosity-temperature change curves of the Chinese medicine self-emulsifying ointments prepared in Examples 1 to 5 and the Chinese medicine ointment prepared in Comparative Example 1 are shown. Fig.11 As shown, all samples have the characteristics of shear thinning. The slopes of the viscosity-shear rate curves of the Chinese medicine self-emulsifying ointment samples prepared based on Examples 1 to 5 are -0.026, -0.026, -0.030, -0.029 and -0.026, respectively. The slope of the viscosity-shear rate curve of the Chinese medicine ointment prepared in Comparative Example 1 is -0.020, which indicates that the viscosity of the Chinese medicine self-emulsifying ointment is significantly lower than that of the Chinese medicine ointment in Comparative Example 1, which is more conducive to application. Fig.12 As shown, the viscosity of the Chinese medicine self-emulsifying ointments prepared in Examples 1 to 5 decreases with increasing temperature and is lower than that of the Chinese medicine ointment in Comparative Example 1.

[0102] Fig.13 and Fig.14 The viscosity-shear rate change curves and viscosity-temperature change curves of the Chinese medicine semi-solid sprays prepared in Examples 8 to 11 and the Chinese medicine ointment prepared in Comparative Example 1 are shown. Fig.13 and Fig.14 As shown, the viscosity of the Chinese medicine semi-solid sprays prepared in Examples 8 and 9 is significantly lower than that of the Chinese medicine ointment in Comparative Example 1, and the viscosity of the Chinese medicine semi-solid sprays prepared in Examples 10 and 11 is close to that of the Chinese medicine ointment in Comparative Example 1, achieving controllable viscosity changes, which can meet the application of different scenarios. Low viscosity can be used for mild skin conditions, and higher viscosity can quickly form a thicker semi-solid film after spraying, which is similar to the effect of an ointment, but does not require manual application, avoiding the inconvenience caused by manual operation of traditional ointments.

[0103] Therefore, the two dosage forms (ointment and spray) can meet different application scenarios, and the Chinese medicine self-emulsifying ointment is easier to apply than the traditional ointment, while the Chinese medicine semi-solid spray, compared with the traditional ointment, avoids cross-infection or secondary injury caused by manual application, and can increase patient compliance.

[0104] 3. Antibacterial performance analysis

[0105] 1. Antibacterial effect of Chinese herbal medicine extracts

[0106] Prepare 40g / L TSA solid medium (purchased from Thermo Fisher Scientific, catalog number CM0131B), sterilize in a high pressure steam sterilizer, prepare 30g / L TSB liquid medium (purchased from Thermo Fisher Scientific, catalog number CM0129B), sterilize in a high pressure steam sterilizer. Take 10μL of the strain (Staphylococcus aureus, S.aureus), add 10mL of TSB liquid medium, and activate for 12 to 24h. Measure the OD value of the activated bacterial solution and dilute it to 1×10 by gradient dilution. 6 CFU / mL, take 100μL of the diluted bacterial solution and add it to the TSA solid culture medium, use sterilized glass beads to disperse it evenly, and pour out the glass beads after coating. Use the punching method to make holes on the TSA solid culture medium after coating the plate, put the Chinese herbal medicine extract (4% Chinese herbal medicine extract aqueous solution) in it, set up 2 to 3 parallel experiments, put it in a 37℃ constant temperature incubator and culture it for 18 to 24 hours, observe and collect photos of the inhibition zone.

[0107] Fig.15 This is a diagram showing the antibacterial zone effect of Chinese herbal extracts on Staphylococcus aureus. As shown in the figure, a 4% aqueous solution of Chinese herbal extracts has a significant antibacterial effect on Staphylococcus aureus.

[0108] 2. Antibacterial effect of Chinese medicine self-emulsifying ointment and Chinese medicine semi-solid spray

[0109] The test method is the same as the evaluation of the antibacterial effect of the Chinese medicine extracts. The antibacterial zone of the Chinese medicine self-emulsifying ointment prepared in Example 2 and the Chinese medicine semi-solid spray prepared in Examples 8 and 9 against Staphylococcus aureus was evaluated.

[0110] Fig.16The figure is a diagram showing the antibacterial zone effect of the Chinese medicine self-emulsifying ointment prepared in Example 2 and the Chinese medicine semi-solid spray prepared in Examples 8 and 9 on Staphylococcus aureus, wherein A and C are respectively the antibacterial zones of the Chinese medicine self-emulsifying ointment prepared in Example 2 and the Chinese medicine ointment prepared in Comparative Example 1 on Staphylococcus aureus, B and D are respectively the antibacterial zones of the anhydrous plant-based semi-solid self-emulsifying matrix prepared in Example 2 and the yellow vaseline of Comparative Example 1 on Staphylococcus aureus, and E and F are respectively the antibacterial zones of the Chinese medicine semi-solid spray prepared in Examples 8 and 9 on Staphylococcus aureus. As shown in the figure, the Chinese medicine self-emulsifying ointment in Example 2 and the Chinese medicine semi-solid spray prepared in Examples 8 and 9 have good antibacterial effects on Staphylococcus aureus ( Fig.16 A, E and F in the figure), and the matrix alone had no antibacterial effect ( Fig.16 B and D in the figure indicate that Chinese herbal extracts dispersed in ointments and sprays can still exert antibacterial effects, and to a certain extent can solve the problem of increased drug resistance caused by antibacterial ointments based mainly on antibiotics.

[0111] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention is described in detail with reference to the aforementioned embodiments, those skilled in the art can still modify the technical solutions described in the aforementioned embodiments or replace some of the technical features therein by equivalents. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A Chinese medicine self-emulsifying ointment, characterized in that: The traditional Chinese medicine self-emulsifying ointment uses water and / or ethanol as a solvent, and comprises 6-26wt% of a solvent, 1-4wt% of a traditional Chinese medicine extract, and 70-90wt% of an anhydrous plant-based semisolid self-emulsifying matrix, wherein the anhydrous plant-based semisolid self-emulsifying matrix comprises 30-45wt% of an anhydrous plant-based oil, 10-25wt% of an emulsifier, 10-25wt% of an auxiliary emulsifier, and 10-25wt% of a thickener.

2. The Chinese medicine self-emulsifying ointment according to claim 1, characterized in that: The traditional Chinese medicine extract is an extract of scutellaria baicalensis, phellodendron chinense and coptis chinensis.

3. The Chinese medicine self-emulsifying ointment according to claim 2, characterized in that: Calculated on the basis of the raw materials used in preparing the Chinese medicine extract, the mass ratio of the scutellaria baicalensis, phellodendron amurense and coptis chinensis is 1:1:

1.

4. The Chinese medicine self-emulsifying ointment according to claim 1, characterized in that: The anhydrous plant-based oil is one of oleyl alcohol, isopropyl myristate, and cocoyl capryloyl caprate; The emulsifier is one of polyoxyethylene 40 hydrogenated castor oil, polyoxyethylene castor oil, polysorbate 20 and polysorbate 80; The auxiliary emulsifier is one of 1,2-propylene glycol, ethoxydiglycol, ethanol, glycerol, polyethylene glycol 400 and polyether L-44; The thickener is one of mono- and distearic acid glyceryl II, poloxamer 407, stearyl alcohol and stearic acid.

5. The Chinese medicine self-emulsifying ointment according to claim 1, characterized in that: The traditional Chinese medicine self-emulsifying ointment comprises 4wt% of extracts of scutellaria baicalensis, phellodendron chinense and coptis chinensis, 16wt% of deionized water, 38wt% of isopropyl myristate, 12wt% of polyoxyethylene castor oil, 18wt% of ethoxydiglycol and 12wt% of glyceryl mono- and distearate II.

6. The method for preparing the Chinese medicine self-emulsifying ointment according to any one of claims 1 to 5, characterized in that: The following steps are involved: (1) crushing Scutellaria baicalensis, Phellodendron amurense and Coptidis chinensis into powder, dispersing the powder in an extraction solvent, heating under reflux, filtering, concentrating and drying to obtain a Chinese medicine extract; (2) mixing anhydrous plant-based oil, an emulsifier, a co-emulsifier and a thickener, heating and stirring until uniform, to obtain anhydrous plant-based semisolid self-emulsifying matrix; (3) dissolving the Chinese herbal extract obtained in step (1) in a solvent, adding the solvent to the anhydrous plant-based semisolid self-emulsifying matrix obtained in step (2), and stirring evenly to obtain a Chinese herbal self-emulsifying ointment.

7. A Chinese medicine semi-solid spray, characterized in that: The Chinese medicine semi-solid spray comprises the Chinese medicine self-emulsifying ointment according to any one of claims 1 to 5 and a propellant, and the mass ratio of the Chinese medicine self-emulsifying ointment to the propellant is 1 to 3:

1.

8. The Chinese medicine semi-solid spray according to claim 7, characterized in that: The propellant is dimethyl ether, alkane or fluorine-containing alkane.

9. The Chinese medicine semi-solid spray according to claim 7, characterized in that: In the Chinese medicine semi-solid spray, the Chinese medicine self-emulsifying ointment comprises 4wt% of extracts of scutellaria baicalensis, phellodendron chinense and coptis chinensis, 16wt% of deionized water, 38wt% of isopropyl myristate, 12wt% of polyoxyethylene castor oil, 18wt% of ethoxydiglycol and 12wt% of mono- and distearic acid glyceryl II; the mass ratio of the Chinese medicine self-emulsifying ointment to the propellant is 2:1.

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