Anhydrous semisolid antibiotic spray preparation and preparation method thereof

Abstract

The invention discloses an anhydrous semisolid antibiotic spray preparation which comprises a self-emulsifying matrix containing antibiotics and a propellant in a mass ratio of (1-3): 1, the antibiotic-containing self-emulsifying matrix is prepared from 0.1 to 3 weight percent of antibiotic, 0.1 to 7 weight percent of local anesthetic and 90 to 99.6 weight percent of anhydrous plant-based semi-solid self-emulsifying matrix. An anhydrous plant-based semi-solid self-emulsifying matrix is used as a dispersing agent of antibiotics, and the stable and low-viscosity anhydrous semi-solid antibiotic spray preparation is obtained by adjusting different proportions of a propellant and the self-emulsifying matrix containing the antibiotics. The low-viscosity emulsion is applied to the skin surface through an aerosol spraying technology, the low-viscosity emulsion quickly forms a high-viscosity semi-solid film after being sprayed, and active ingredients such as antibiotics can be uniformly coated on an affected part, so that wound pain and secondary infection caused by direct contact are avoided, the patient compliance is improved, and the application prospect is wide. The antibacterial effect is obviously superior to that of commercially available compound polymyxin B ointment.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceutical preparations, and in particular to an anhydrous semisolid antibiotic spray preparation and a preparation method thereof. Background Art

[0002] Antibiotics are a class of drugs used to kill or inhibit the growth of bacteria, mainly used to treat infections caused by bacteria. Traditional semi-solid antibiotic preparations (such as ointments, creams, gels) are the main form of topical antibacterial drugs and are widely used to treat and prevent skin infections.

[0003] Existing antibiotic ointment preparations are mostly based on vaseline and liquid paraffin. The Chinese patent document with publication number CN118286387A discloses an antibacterial ointment and its preparation method and application. The antibacterial ointment includes polymyxin B sulfate, mupirocin, docusate sodium, white vaseline, lanolin, light liquid paraffin, and is sequentially sterilized at high temperature-mixed and stirred-high temperature homogenized to obtain the antibacterial ointment. The antibacterial ointment is used in drugs for treating bacterial infections. However, due to the use of white vaseline, lanolin, and light liquid paraffin as the matrix, the drug dispersibility is poor.

[0004] Compound polymyxin B ointment is a compound preparation formed by combining polymyxin B sulfate with other antibiotics, including polymyxin B sulfate, bacitracin, neomycin sulfate and caine drugs. Among them, polymyxin B sulfate kills bacteria by destroying bacterial cell membranes, mainly targeting Gram-negative bacteria; bacitracin mainly targets Gram-positive bacteria, treats local bacterial infections, especially mixed infections of multiple bacteria (including Gram-negative and Gram-positive bacteria), and can enhance the antibacterial range; neomycin sulfate is a broad-spectrum aminoglycoside antibiotic that inhibits bacterial protein synthesis and is effective against a variety of bacteria; caine drugs: as local anesthetics, help relieve pain and discomfort at the site of infection.

[0005] The Chinese patent document with publication number CN106075394A discloses an ointment preparation and its preparation method and application, belonging to the technical field of pharmaceutical preparations. The ointment preparation includes a matrix, polymyxin B sulfate, neomycin sulfate, bacitracin and a hemostatic agent, wherein the polymyxin B sulfate, neomycin sulfate, bacitracin and the hemostatic agent are uniformly dispersed in the matrix, and the components of the matrix and the weight percentages in each gram of the ointment preparation are respectively 5% to 7.5% of liquid paraffin, 2% to 5% of propylene glycol, 0.01% to 0.03% of methyl paraben, and white vaseline is added to the prescription amount. With vaseline and liquid paraffin as the matrix, the drug dispersibility is not good, there are drug crystals, and the ointment preparation needs to be applied manually, which is difficult to be evenly applied on a large area, deep layer or irregular wound surface, and manual operation may cause cross infection and secondary injury, affecting the treatment effect and patient compliance.

[0006] In order to overcome the limitations of traditional semi-solid antibiotic preparations, anhydrous semi-solid antibiotic spray preparations came into being. Although traditional matrices such as vaseline can significantly improve the stability of drugs, direct mixing of such matrices with propellants will face the problem of emulsion stratification and fail to form a stable emulsion, which limits the use of semi-solid sprays. Therefore, it is necessary to develop a matrix that can directly form a stable emulsion with the propellant to solve the problem of preparing anhydrous semi-solid spray preparations. Summary of the invention

[0007] In order to solve the above technical problems, the present invention provides an anhydrous semisolid antibiotic spray preparation. By adjusting different ratios of the propellant and the self-emulsifying matrix containing the antibiotic, a stable anhydrous semisolid antibiotic spray preparation is obtained. The spray preparation has good dispersibility and antibacterial effect.

[0008] A water-free semi-solid antibiotic spray preparation comprises a self-emulsifying matrix containing antibiotics and a propellant, wherein the mass ratio of the self-emulsifying matrix containing antibiotics to the propellant is 1-3:1, and the self-emulsifying matrix containing antibiotics comprises 0.1-3wt% of antibiotics, 0.1-7wt% of local anesthetics and 90-99.6wt% of a water-free plant-based semi-solid self-emulsifying matrix.

[0009] In the present invention, an anhydrous plant-based semisolid self-emulsifying matrix is ​​used as a dispersant for antibiotics, and the antibiotics have good dispersibility in the anhydrous plant-based semisolid self-emulsifying matrix without obvious crystallization. The self-emulsifying matrix containing antibiotics can directly form a stable low-viscosity emulsion with the propellant to avoid the stratification of the emulsion. The present invention obtains a stable anhydrous semisolid antibiotic spray preparation by adjusting different ratios of the propellant and the self-emulsifying matrix containing the antibiotic.

[0010] 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 low-viscosity emulsion quickly forms a high-viscosity semi-solid film after spraying, and active ingredients such as antibiotics can be evenly applied to the affected area, avoiding direct contact to cause wound pain and secondary infection, improving patient compliance, and the antibacterial effect is significantly better than the commercially available compound polymyxin B ointment.

[0011] Preferably, the anhydrous plant-based semisolid self-emulsifying matrix comprises 40-60 wt % of anhydrous plant-based oil, 8-30 wt % of a surfactant, 10-30 wt % of a co-surfactant and 10-20 wt % of a thickener.

[0012] Further preferably, the anhydrous plant-based oil is one of oleyl alcohol (OA), isopropyl myristate (IPM), cocoyl capryloyldecanoate (3C) and glyceryl triacetate (GTA).

[0013] Further preferably, the surfactant is one of polyoxyethylene castor oil (ELP), polysorbate 80 (PS80), polyethylene glycol cetearyl alcohol 20 (CS20) and polyoxyethylene 40 hydrogenated castor oil (RH40).

[0014] More preferably, the co-surfactant is one of 1,2-propylene glycol (PG), ethoxydiglycol and ethanol.

[0015] More preferably, the thickener is one of glyceryl mono- and distearate II (GMS II), stearyl alcohol and stearic acid.

[0016] Preferably, the propellant is one of dimethyl ether (DME), alkane and fluorine-containing alkane.

[0017] More preferably, the antibiotic-containing self-emulsifying base comprises 1.3 wt % antibiotics, 4.0 wt % local anesthetics, 50 wt % oleyl alcohol, 15 wt % polyethylene glycol cetearyl alcohol 20, 14.7 wt % 1,2-propylene glycol and 15 wt % glyceryl mono- and distearate II, and the mass ratio of the antibiotic-containing self-emulsifying base to the propellant is 29:13.

[0018] Preferably, the obtained anhydrous semisolid antibiotic spray preparation has good dispersibility and good antibacterial activity.

[0019] Preferably, the antibiotic is at least one of bacitracin, bacitracin zinc, neomycin sulfate, and polymyxin B sulfate.

[0020] More preferably, the antibiotic is a combination of 0.07-1.6 wt% bacitracin, 0.03-0.8 wt% neomycin sulfate, and 0.01-0.25 wt% polymyxin B sulfate.

[0021] Preferably, the local anesthetic is one of lidocaine, lidocaine hydrochloride, procaine hydrochloride or bupivacaine.

[0022] More preferably, the antibiotics are 0.83wt% bacitracin, 0.35wt% neomycin sulfate and 0.12wt% polymyxin B sulfate, and the local anesthetic is 4wt% lidocaine hydrochloride.

[0023] The present invention also provides a method for preparing the above-mentioned anhydrous semisolid antibiotic spray preparation. The preparation method directly adds a propellant into a self-emulsifying matrix containing antibiotics to prepare a stable anhydrous semisolid antibiotic spray preparation. The preparation method is simple and easy to operate.

[0024] A method for preparing an anhydrous semisolid antibiotic spray preparation comprises the following steps:

[0025] (1) mixing anhydrous plant-based oil, a surfactant, a co-surfactant and a thickener, heating and stirring until a uniform state is obtained to obtain anhydrous plant-based semisolid self-emulsifying matrix;

[0026] (2) dispersing the antibiotic and the local anesthetic into the anhydrous plant-based semisolid self-emulsifying matrix obtained in step (1) to obtain a self-emulsifying matrix containing the antibiotic;

[0027] (3) Filling the self-emulsifying matrix containing antibiotics obtained in step (2) with a propellant to obtain an anhydrous semisolid antibiotic spray preparation.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] (1) In the present invention, an anhydrous plant-based semisolid self-emulsifying matrix is ​​used as a dispersant for antibiotics. The antibiotics have good dispersibility in the anhydrous plant-based semisolid self-emulsifying matrix without obvious crystallization; the self-emulsifying matrix containing antibiotics can directly form a stable low-viscosity emulsion with the propellant to avoid stratification of the emulsion.

[0030] (2) The present invention directly adds a propellant to a self-emulsifying matrix containing an antibiotic to prepare a stable anhydrous semisolid antibiotic spray preparation, and the preparation method is simple and easy to operate. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 These are pictures of the anhydrous semisolid antibiotic spray preparations prepared in Examples 1 to 5, wherein from left to right they are Examples 1 to 5, the upper picture is a front view, and the lower picture is a bottom photograph.

[0032] Figure 2 It is a picture of the anhydrous semisolid antibiotic spray preparation of Comparative Example 4, wherein the upper picture is a front view and the lower picture is a bottom photo.

[0033] Figure 3 It is a picture of the compound polymyxin-vaseline spray preparation of comparative example 5, wherein the upper picture is a front view and the lower picture is a bottom photograph.

[0034] Figure 4 This is a photo of the spraying of the anhydrous semisolid antibiotic spray preparation of Example 2.

[0035] Figure 5 The following are pictures showing the effects of the anhydrous semi-solid antibiotic spray preparations of Examples 1 to 3 after spraying, with Examples 1 to 3 being shown from left to right.

[0036] Figure 6The figures are the antibacterial zone effect diagrams of the anhydrous semisolid antibiotic spray preparations prepared in Examples 1 to 3 and the ointment preparations in Comparative Examples 1 to 3 on Escherichia coli, wherein A to F are Examples 1 to 3 and Comparative Examples 1 to 3, respectively, and G is a quantitative diagram of the antibacterial zone areas of A to F.

[0037] Figure 7 The figures are the antibacterial zone effect diagrams of the anhydrous semisolid antibiotic spray preparations prepared in Examples 1 to 3 and the ointment preparations in Comparative Examples 1 to 3 on Staphylococcus aureus, wherein A to F are Examples 1 to 3 and Comparative Examples 1 to 3, respectively, and G is a quantitative diagram of the antibacterial zone areas of A to F.

[0038] Figure 8 The viscosity-shear rate variation curves of the anhydrous semisolid antibiotic spray preparations prepared in Examples 1 to 3, Comparative Example 1 (compound polymyxin B ointment), and Comparative Example 2 (NEOSPORIN).

[0039] Fig. 9 The viscosity-temperature curves of the anhydrous semisolid antibiotic spray preparations prepared in Examples 1 to 3, Comparative Example 1 (compound polymyxin B ointment), and Comparative Example 2 (NEOSPORIN).

[0040] Fig.10 XRD spectra of the anhydrous semisolid antibiotic spray preparations prepared in Examples 2 and 3, Comparative Example 1 (compound polymyxin B ointment), and Comparative Example 2 (NEOSPORIN). DETAILED DESCRIPTION

[0041] 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.

[0042] The raw materials used in the present invention are all commercially available.

[0043] Example 1

[0044] (1) 50 wt% of oleyl alcohol (OA), 19.7 wt% of polyoxyethylene (35) castor oil (ELP), 10 wt% of 1,2-propylene glycol (PG) and 15 wt% of glyceryl mono- and distearate II (GMS II) were heated and stirred at 70° C. for 30 min until a uniform phase was obtained to obtain an anhydrous plant-based semisolid self-emulsifying matrix;

[0045] (2) dispersing 0.83 wt % of bacitracin, 0.35 wt % of neomycin sulfate, 0.12 wt % of polymyxin B sulfate and 4 wt % of lidocaine hydrochloride into the anhydrous plant-based semisolid self-emulsifying matrix obtained in step (1) to obtain a self-emulsifying matrix containing antibiotics;

[0046] (3) The antibiotic-containing self-emulsifying matrix obtained in step (2) is transferred into a GK-500 pressure-resistant bottle, the bottle mouth is sealed, and after cooling to room temperature, dimethyl ether (DME) is added into the bottle, wherein the mass ratio of the antibiotic-containing self-emulsifying matrix to dimethyl ether is 25:9; the mixture is fully mixed and shaken evenly on a shaker to obtain an anhydrous semisolid antibiotic spray preparation.

[0047] Embodiments 2 to 5

[0048] The preparation methods of Examples 2 to 5 are the same as that of Example 1, and the differences are shown in the table below.

[0049] Table 1: Differences in the preparation methods of the anhydrous semisolid antibiotic spray preparations of Examples 1 to 5

[0050]

[0051] Comparative Example 1: Commercially available compound polymyxin B ointment (purchased from Funo, batch number 20220313)

[0052] The active ingredients are: bacitracin (0.83wt%), neomycin sulfate (0.35wt%), polymyxin B sulfate (0.06wt%), lidocaine hydrochloride (4wt%), and the rest is vaseline matrix.

[0053] Comparative Example 2: Commercially available product NEOSPORIN (purchased from Johnson & Johnson, batch number 30041007)

[0054] The active ingredients are: bacitracin zinc (0.7wt%), neomycin sulfate (0.35wt%), polymyxin B sulfate (0.12wt%), pramoxine hydrochloride (1wt%), and the rest is vaseline matrix.

[0055] Comparative Example 3: Compound polymyxin-yellow vaseline base ointment

[0056] Bacitracin (0.83 wt%), neomycin sulfate (0.35 wt%), polymyxin B sulfate (0.12 wt%), and lidocaine hydrochloride (4 wt%) are dispersed in a vaseline matrix to obtain a compound polymyxin-yellow vaseline matrix ointment.

[0057] Comparative Example 4

[0058] The preparation method is the same as that of Example 5, except that the surfactant is RH40, and the mass ratio of the self-emulsifying matrix containing antibiotics to DME is 1:4.

[0059] Comparative Example 5

[0060] The preparation method is the same as that of Example 1, except that the anhydrous plant-based semisolid self-emulsifying matrix is ​​replaced with a vaseline matrix to obtain a compound polymyxin-vaseline spray preparation.

[0061] Sample analysis

[0062] 1. Appearance Observation

[0063] The appearances of the anhydrous semisolid antibiotic spray preparations prepared in Examples 1 to 5, the anhydrous semisolid antibiotic spray preparation of Comparative Example 4, and the compound polymyxin-vaseline spray preparation of 5 were observed.

[0064] Figure 1 : is a picture of the anhydrous semi-solid antibiotic spray preparation prepared in Examples 1 to 5, wherein from left to right are Examples 1 to 5, as shown in FIG. Figure 1 As shown, the anhydrous semi-solid antibiotic spray preparations prepared in Examples 1 to 5 are all milky white, with no obvious stratification phenomenon and no obvious particle precipitation.

[0065] Figure 2 and Figure 3 The pictures are respectively the anhydrous semisolid antibiotic spray preparation of comparative example 4 and the compound polymyxin-vaseline spray preparation of comparative example 5, as shown in FIG. Figure 2 and Figure 3 As shown, Comparative Example 4 has slight particle precipitation, and Comparative Example 5 is observed to have obvious stratification phenomenon and there are obvious particles at the bottom that are not completely dissolved.

[0066] 2. Spraying status

[0067] Figure 4 This is a spray photo of the anhydrous semisolid antibiotic spray preparation of Example 2. Figure 5 The following are the effects of the anhydrous semi-solid antibiotic spray preparations of Examples 1 to 3 after spraying, from left to right are Examples 1 to 3. Figure 4 As shown, the prepared anhydrous semi-solid antibiotic spray preparation can be converted into a fine mist spray by the pressure of the spray bottle, such as Figure 5 As shown, after the anhydrous semi-solid antibiotic spray preparations of Examples 1 to 3 are sprayed, the low-boiling-point propellant evaporates quickly to form a high-viscosity semi-solid ointment, thereby avoiding manual application.

[0068] 3. Evaluation of antibacterial effect

[0069] The antibacterial effects of the anhydrous semisolid antibiotic spray preparations prepared in Examples 1 to 3 and the ointment preparations in Comparative Examples 1 to 3 were evaluated. First, 40 g / L of TSA solid culture medium (purchased from Thermo Fisher Scientific, catalog number CM0131B) was prepared and sterilized in a high-pressure steam sterilizer; 30 g / L of TSB liquid culture medium (purchased from Thermo Fisher Scientific, catalog number CM0129B) was prepared and sterilized in a high-pressure steam sterilizer; 10 μL of bacterial strains (Escherichia coli and Staphylococcus aureus) were taken respectively, and 10 mL of TSB liquid culture medium was added to activate for 12 to 24 hours; the OD value of the activated bacterial solution was measured and diluted to 1×10 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, fill the sample to ensure the same amount of sample addition; put it in a 37℃ constant temperature incubator and culture it for 18 to 24 hours. Observe and collect photos of the inhibition zone, and calculate the area of ​​the inhibition zone by comparing the size of the inhibition zone through Image J.

[0070] Figure 6 The following are the antibacterial zone effect diagrams of the anhydrous semi-solid antibiotic spray preparations prepared in Examples 1 to 3 and the ointment preparations in Comparative Examples 1 to 3 on Escherichia coli, wherein A to F are respectively Examples 1 to 3 and Comparative Examples 1 to 3, and G is a quantitative diagram of the antibacterial zone area of ​​A to F. The antibacterial zone area was statistically calculated by Image J, and the results are as follows: Figure 6 As shown in the figure, the anhydrous semisolid antibiotic spray preparations prepared based on Examples 1 to 3 have a larger inhibition zone area against Escherichia coli than the ointment preparations of Comparative Examples 1 to 3, wherein the average inhibition zone area of ​​Comparative Examples 1, 2 and 3 is 1.6±0.5cm 2 , 1.5±0.4cm 2 and 1.1±0.5cm 2 The average inhibition zone areas of Examples 1 to 3 against Escherichia coli were 4.9±0.3 cm 2 、5.6±0.7cm 2 and 4.7±0.2cm 2 Therefore, the antibacterial effects of Examples 1 to 3 on Escherichia coli are significantly better than those of Comparative Examples 1 to 3.

[0071] Figure 7The following are the antibacterial zone effect diagrams of the anhydrous semi-solid antibiotic spray preparations prepared in Examples 1 to 3 and the ointment preparations in Comparative Examples 1 to 3 on Staphylococcus aureus, wherein A to F are respectively Examples 1 to 3 and Comparative Examples 1 to 3, and G is a quantitative diagram of the antibacterial zone area of ​​A to F. The antibacterial zone area was statistically calculated by Image J, and the results are as follows: Figure 7 As shown in the figure, the anhydrous semisolid antibiotic spray preparations prepared based on Examples 1 to 3 have a larger inhibition zone area against Staphylococcus aureus than the ointment preparations of Comparative Examples 1 to 3, wherein the average inhibition zone area of ​​Comparative Examples 1, 2 and 3 is 1.8±1.1 cm 2 , 2.3±0.3cm 2 and 0.8±0.5cm 2 The average inhibition zone area of ​​Examples 1 to 3 against Staphylococcus aureus was 5.4±0.4 cm 2 、6.2±0.3cm 2 and 6.0±0.3cm 2 Therefore, the antibacterial effects of Examples 1-3 on Staphylococcus aureus are significantly better than those of Comparative Examples 1-3.

[0072] 4. Viscosity evaluation

[0073] The changes of "viscosity with shear rate" and "viscosity with temperature" of the anhydrous semi-solid antibiotic spray preparations prepared in Examples 1 to 3 and Comparative Example 1 (compound polymyxin B ointment) and Comparative Example 2 (NEOSPORIN) were tested using a rotational rheometer. A small amount of the above sample (sprayed on a culture dish in advance) was transferred to a 20 mm 0° flat plate, using the Flow-ramp mode, a gap value of 500 μm, a temperature of 25°C, and a shear rate of 0.1 to 100 s -1 ; The "viscosity-shear rate" curve was obtained by testing. Take a small amount of the above sample and place it on a 20mm 0° flat plate. Use the Flow-ramp Temperature mode, the gap value is 500μm, and the shear rate is set to 1.25s -1 , the temperature change is set to 20-50°C; the test obtains the "viscosity-temperature" change curve.

[0074] Figure 8 The viscosity-shear rate variation curves of Examples 1 to 3 and Comparative Examples 1 and 2 are shown in FIG. Figure 8 As shown, the viscosity of the anhydrous semi-solid antibiotic spray preparations prepared in Examples 1 to 3 is lower than that of the commercially available ointment preparations in Comparative Examples 1 and 2, wherein the viscosity of Example 2 is lower than that of the commercially available ointment preparations in Comparative Examples 1 and 2 at a shear rate of about 4 s -1 When , its viscosity is 36Pa·s, and the viscosities of Comparative Example 2 and Comparative Example 1 are 52Pa·s and 181Pa·s, respectively.

[0075] Fig. 9 The viscosity-temperature curves of Examples 1 to 3 and Comparative Examples 1 and 2 are shown in FIG. Fig. 9 As shown, the viscosity of the anhydrous semisolid antibiotic spray preparations prepared in Examples 1 to 3 is comparable to the viscosity of the ointment preparation in Comparative Example 2, wherein the viscosity of Example 1 is 10 Pa·s at a temperature of 36° C., and the viscosities of Comparative Example 1 and Comparative Example 2 are 69 Pa·s and 16 Pa·s, respectively.

[0076] Therefore, compared with commercially available ointment preparations, the anhydrous semisolid antibiotic spray preparation of the present invention has lower viscosity and a more delicate spraying effect, while also retaining a certain viscosity, thereby ensuring good drug adhesion and covering effect.

[0077] 5. Dispersion Evaluation

[0078] By X-ray diffraction analysis (XRD), with compound antibiotics (0.83wt% bacitracin, 0.35wt% neomycin sulfate, 0.12wt% polymyxin B sulfate and 4wt% lidocaine hydrochloride) as controls, the anhydrous semisolid antibiotic spray preparations prepared in Examples 2 and 3 and their blank preparations (anhydrous plant-based semisolid self-emulsifying matrix), Comparative Example 5, and blank vaseline matrix, Comparative Example 1 (compound polymyxin B ointment), and Comparative Example 2 (NEOSPORIN) were evaluated for dispersibility. First, a small amount of the above samples was taken, placed on the sample stage of XRD, and Cu-Kα radiation was used, the current was 40mA, the voltage was 40kV, and the rate of 4° / min was used to scan from 10° to 40°.

[0079] Fig.10 The XRD spectra of the anhydrous semisolid antibiotic spray preparations prepared in Examples 2 and 3, Comparative Example 1 (compound polymyxin B ointment), and Comparative Example 2 (NEOSPORIN), wherein the compound antibiotic is used as a reference substance, and the commercially available compound polymyxin B ointment, NEOSPORIN ointment, and Comparative Example 5 prepared with vaseline as a matrix have obvious diffraction peaks at about 2θ=16°, which are the diffraction peaks of the compound antibiotics, indicating that the commercially available compound polymyxin B ointment, NEOSPORIN ointment, and Comparative Example 5 prepared with vaseline as a matrix have a certain degree of crystallinity and poor dispersibility, which may be caused by the generation of local crystallization; while Examples 2 and 3 have no obvious diffraction peaks at about 2θ=16°, indicating that their internal structures are uniform, and compared with traditional ointments, the anhydrous semisolid antibiotic spray preparation of the present invention has good dispersibility.

[0080] 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. An anhydrous semisolid antibiotic spray preparation, characterized in that: The invention comprises a self-emulsifying matrix containing antibiotics and a propellant, wherein the mass ratio of the self-emulsifying matrix containing antibiotics to the propellant is 1-3:1, and the self-emulsifying matrix containing antibiotics comprises 0.1-3wt% of antibiotics, 0.1-7wt% of local anesthetics and 90-99.6wt% of anhydrous plant-based semi-solid self-emulsifying matrix.

2. The anhydrous semisolid antibiotic spray preparation according to claim 1, characterized in that: The anhydrous plant-based semisolid self-emulsifying matrix comprises 40-60 wt % of anhydrous plant-based oil, 8-30 wt % of a surfactant, 10-30 wt % of an auxiliary surfactant and 10-20 wt % of a thickener.

3. The anhydrous semisolid antibiotic spray preparation according to claim 2, characterized in that: The anhydrous plant-based oil is one of oleyl alcohol, isopropyl myristate, cocoyl capryloyl caprate and triacetin; The surfactant is one of polyoxyethylene castor oil, polysorbate 80, macrogol cetostearyl ether 20 and polyoxyethylene 40 hydrogenated castor oil; The co-surfactant is one of 1,2-propylene glycol, ethoxydiglycol and ethanol; The thickener is one of mono- and distearic acid glyceryl ester II, stearyl alcohol and stearic acid.

4. The anhydrous semisolid antibiotic spray preparation according to claim 1, characterized in that: The propellant is one of dimethyl ether, alkane and fluorine-containing alkane.

5. The anhydrous semisolid antibiotic spray preparation according to claim 1, characterized in that: The antibiotic-containing self-emulsifying matrix comprises 1.3 wt% antibiotics, 4.0 wt% local anesthetics, 50 wt% oleyl alcohol, 15 wt% polyethylene glycol cetearyl alcohol ether 20, 14.7 wt% 1,2-propylene glycol and 15 wt% mono- and distearic acid glyceryl II, and the mass ratio of the antibiotic-containing self-emulsifying matrix to the propellant is 29:

13.

6. The anhydrous semisolid antibiotic spray preparation according to claim 1, characterized in that: The antibiotic is at least one of bacitracin, bacitracin zinc, neomycin sulfate and polymyxin B sulfate.

7. The anhydrous semisolid antibiotic spray preparation according to claim 6, characterized in that: The antibiotic is a combination of 0.07-1.6 wt% bacitracin, 0.03-0.8 wt% neomycin sulfate and 0.01-0.25 wt% polymyxin B sulfate.

8. The anhydrous semisolid antibiotic spray preparation according to claim 1, characterized in that: The local anesthetic is one of lidocaine, lidocaine hydrochloride, procaine hydrochloride or bupivacaine.

9. The anhydrous semisolid antibiotic spray preparation according to claim 5, characterized in that: The antibiotics are 0.83wt% bacitracin, 0.35wt% neomycin sulfate and 0.12wt% polymyxin B sulfate, and the local anesthetic is 4wt% lidocaine hydrochloride.

10. The method for preparing the anhydrous semisolid antibiotic spray preparation according to any one of claims 1 to 9, characterized in that: The following steps are involved: (1) mixing anhydrous plant-based oil, a surfactant, a co-surfactant and a thickener, heating and stirring until a uniform state is obtained to obtain anhydrous plant-based semisolid self-emulsifying matrix; (2) dispersing the antibiotic and the local anesthetic into the anhydrous plant-based semisolid self-emulsifying matrix obtained in step (1) to obtain a self-emulsifying matrix containing the antibiotic; (3) Filling the self-emulsifying matrix containing antibiotics obtained in step (2) with a propellant to obtain an anhydrous semisolid antibiotic spray preparation.

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