Composition containing compound polymyxin B and preparation method thereof

Abstract

The invention provides a composition containing compound polymyxin B and a preparation method of the composition. Carbomer is adopted as a gel type matrix and is subjected to high-pressure homogeneous dispersion, and the addition amount of the Carbomer and high-pressure homogeneous dispersion parameter conditions are controlled, so that lidocaine hydrochloride is uniformly dispersed in the matrix; the composition has good content uniformity, rheological property and in-vitro release effect, can form a layer of transparent or semitransparent gel on the skin after being used by a patient, has good moisture retention, air permeability and sterilization effect, can delay the residence time of the medicine on the skin surface and increase the curative effect of the medicine, and is few in component variety, low in cost and suitable for popularization and application. The method is suitable for large-scale industrial production.

Description

Technical Field

[0001] The present invention belongs to the technical field of drug preparation, and particularly relates to a composition containing compound polymyxin B and a preparation method thereof. Background Art

[0002] Compound polymyxin B ointment is a compound preparation composed of polymyxin B sulfate, bacitracin, neomycin sulfate, and lidocaine hydrochloride. It is suitable for preventing bacterial infections of wounds such as skin cuts, abrasions, burns, or surgical wounds. It can also be used temporarily to relieve pain and discomfort of skin wounds.

[0003] Patent CN106075394A discloses an ointment formulation, its preparation method, and its use. Using vaseline as a matrix, it is susceptible to reaction temperature and can cause lidocaine hydrochloride to clump and harden, preventing it from being evenly dispersed within the matrix. Patent CN108434437A discloses a compound ointment formulation and its preparation method. This formulation addresses the lidocaine hydrochloride clumping issue by adding another matrix, but the composition is complex and the excessive addition of materials leads to high production costs. Summary of the Invention

[0004] The object of the present invention is to provide a composition containing compound polymyxin B on the basis of the existing technology. Carbomer is used as a gel-type matrix and high-pressure homogenization is used for dispersion, so that lidocaine hydrochloride is uniformly dispersed in the matrix. The composition has good content uniformity, rheological properties and in vitro release effect. After use, a layer of transparent or translucent gel is formed on the skin of the patient. The composition has good moisturizing properties, air permeability and sterilization effect, and can delay the retention time of the drug on the skin surface, thereby increasing the drug efficacy. The composition has fewer component types, low cost and is suitable for large-scale industrial production.

[0005] The second object of the present invention is to provide a method for preparing the above-mentioned composition containing compound polymyxin B.

[0006] The technical solutions of the present invention are as follows:

[0007] A composition containing compound polymyxin B is mainly prepared from polymyxin B sulfate, neomycin sulfate, bacitracin, lidocaine hydrochloride and carbomer. During its preparation process, carbomer is first dissolved in water and stirred until it is completely swollen to obtain a dispersion liquid, then lidocaine hydrochloride is added and high-pressure homogenization is performed to obtain a suspension, which is then stirred and sheared mixed with polymyxin B sulfate, bacitracin and neomycin sulfate to prepare an ointment, which is then encapsulated to obtain the ointment.

[0008] In a preferred embodiment, during high-pressure homogenization and dispersion, the high-pressure homogenization pressure is 0.1 MPa-0.4 MPa, and the number of high-pressure homogenizations is 2-4 times; during stirring and shearing mixing, the shear speed is 1.5k rpm-4.5k rpm, and the shear time is 10-60 min.

[0009] In a preferred embodiment, the particle size D of lidocaine hydrochloride is 90 40-60μm.

[0010] In a preferred embodiment, the composition containing compound polymyxin B provided by the present invention contains the following components by weight per gram of the composition: 4500-6000 units of polymyxin B sulfate, 3150-4200 units of neomycin sulfate, 450-600 units of bacitracin, 36-44 mg of lidocaine hydrochloride, and 2.0-5.5 mg of carbomer.

[0011] In a more preferred embodiment, the composition containing compound polymyxin B provided by the present invention contains the following components by weight per gram of the composition: 4800-5200 units of polymyxin B sulfate, 3400-3600 units of neomycin sulfate, 480-520 units of bacitracin, 38-42 mg of lidocaine hydrochloride, and 2.5-5.0 mg of carbomer.

[0012] In a particularly preferred embodiment, the composition containing compound polymyxin B provided by the present invention contains the following components by weight per gram of the composition: 5000 units of polymyxin B sulfate, 3500 units of neomycin sulfate, 500 units of bacitracin, 40 mg of lidocaine hydrochloride and 4.0 mg of carbomer.

[0013] The present invention also provides a method for preparing the above-mentioned composition containing compound polymyxin B, comprising the following steps:

[0014] (1) Matrix dispersion: Dissolve carbomer in water and stir until it is completely swollen to obtain a dispersion;

[0015] (2) Dispersing the active ingredient: adding lidocaine hydrochloride to the dispersion obtained in step (1) and performing high-pressure homogenization to obtain a suspension, wherein the high-pressure homogenization pressure is 0.1 MPa-0.4 MPa and the number of high-pressure homogenization times is 2-4 times;

[0016] (3) adding polymyxin B sulfate, bacitracin and neomycin sulfate to the suspension obtained in step (2), stirring and shearing to prepare an ointment, the shear speed being 1.5k rpm-4.5k rpm, and the shear time being 10-60 min;

[0017] (4) Control the temperature of the ointment obtained in step (3) to 40-45° C. and seal it with an ointment tube.

[0018] In a preferred embodiment, in step (2), the high-pressure homogenization pressure is 0.2 MPa-0.3 MPa, more preferably 0.3 MPa.

[0019] In a preferred embodiment, in step (2), the particle size D of lidocaine hydrochloride is 90 40-60μm.

[0020] In a preferred embodiment, in step (2), the high-pressure homogenization is performed three times.

[0021] In a preferred embodiment, in step (3), the shearing rotation speed is 2k rpm-4k rpm, more preferably 3k rpm.

[0022] In a preferred embodiment, in step (3), the shearing time is 20-40 min, more preferably 30 min.

[0023] Adopt the technical scheme of the present invention, the advantages are as follows:

[0024] The invention provides a composition containing compound polymyxin B. Carbomer is used as a gel-type matrix and high-pressure homogenization is performed for dispersion. The amount of carbomer added and the parameters of the high-pressure homogenization dispersion are controlled so that lidocaine hydrochloride is uniformly dispersed in the matrix. The composition has good content uniformity, rheological properties and in vitro release effect. After use, a layer of transparent or translucent gel is formed on the skin of a patient. The composition has good moisture retention, air permeability and sterilization effect, can delay the retention time of the drug on the skin surface, and increases the efficacy of the drug. The composition has fewer component types, low cost and is suitable for large-scale industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 is an amplitude scan graph of Examples 1-3 and Comparative Examples 1-2;

[0026] Figure 2 is a frequency sweep diagram of Examples 1-3 and Comparative Examples 1-2;

[0027] Figure 3 Flow curve diagrams of Examples 1-3 and Comparative Examples 1-2;

[0028] Figure 4 is the amplitude scan diagram of Example 5-7;

[0029] Figure 6 is a frequency scan diagram of Example 5-7;

[0030] Figure 8 is a flow curve diagram of Example 5-7;

[0031] Figure 5is the amplitude scan graph of Comparative Examples 3-6;

[0032] Figure 7 is a frequency scan diagram of Comparative Examples 3-6;

[0033] Figure 9 It is the flow curve diagram of comparative example 3-6. DETAILED DESCRIPTION

[0034] The present invention can be better understood according to the following examples. However, it is easy for those skilled in the art to understand that the contents described in the examples are only used to illustrate the present invention, and should not and will not limit the present invention described in detail in the claims.

[0035] Examples 1-3

[0036] A composition containing compound polymyxin B, wherein each gram of the composition contains the following components by weight. The components and weights of Examples 1-3 are specifically shown in Table 1.

[0037] Table 1 Components and dosage

[0038] Components Example 1 Example 2 Example 3 Polymyxin B sulfate 5000U 5000U 5000U Bacitracin 500U 500U 500U Neomycin sulfate 3500U 3500U 3500U <![CDATA[Lidocaine hydrochloride (particle size D 90 is 40 - 60 μm)]]> 40mg / g 40mg / g 40mg / g Carbomer 4mg / g 2.5mg / g 5.0mg / g Water for injection Increase to 1g Increase to 1g Increase to 1g

[0039] The method for preparing the composition containing compound polymyxin B in Example 1 comprises the following steps:

[0040] (1) Matrix dispersion: Dissolve carbomer in water and stir until it is completely swollen to obtain a dispersion;

[0041] (2) Dispersing the active ingredient: adding lidocaine hydrochloride to the dispersion obtained in step (1) and performing high-pressure homogenization to obtain a suspension. The high-pressure homogenization pressure is 0.3 MPa and the number of high-pressure homogenization times is 3;

[0042] (3) adding polymyxin B sulfate, bacitracin and neomycin sulfate to the suspension obtained in step (2), stirring and shearing to prepare an ointment, the shear speed is 3k rpm, and the shear time is 30 min;

[0043] (4) Control the temperature of the ointment obtained in step (3) to 40-45° C. and seal it in an aluminum medicinal ointment tube, 15 g per tube.

[0044] The difference between Example 2-3 and Example 1 is that the amount of carbomer used is different, and the preparation method is the same as that of Example 1.

[0045] Examples 4-7

[0046] The difference between Example 4 and Example 1 is that the high-pressure homogenization is performed twice, and the types and amounts of the components and the preparation method are the same as those in Example 1.

[0047] The difference between Example 5 and Example 1 is that the high-pressure homogenization is performed four times, and the types and amounts of the components and the preparation method are the same as those in Example 1.

[0048] The difference between Example 6 and Example 1 is that the shear speed is 2k rpm, and the types and amounts of the components and the preparation method are the same as those in Example 1.

[0049] The difference between Example 7 and Example 1 is that the shear speed is 4k rpm, and the types and amounts of the components and the preparation method are the same as those in Example 1.

[0050] Comparative Example 1-2

[0051] A composition containing compound polymyxin B, wherein each gram of the composition contains the following components by weight. The components and weights of Comparative Examples 1-2 are specifically shown in Table 2.

[0052] Table 2 Components and dosage

[0053] Components Comparative Example 1 Comparative Example 2 Polymyxin B sulfate 5000U 5000U Bacitracin 500U 500U Neomycin sulfate 3500U 3500U <![CDATA[Lidocaine hydrochloride (particle size D 90 is 40 - 60 μm)]]> 40mg / g 40mg / g Carbomer 1mg / g 6mg / g Water for injection Increase to 1g Increase to 1g

[0054] The difference between Comparative Example 1-2 and Example 1 is that the amount of carbomer used is different, and the preparation method is the same as that of Example 1.

[0055] Comparative Examples 3-6

[0056] The difference between Comparative Example 3 and Example 1 is that the high-pressure homogenization was performed once, and the types and amounts of the components and the preparation method were the same as those in Example 1.

[0057] The difference between Comparative Example 4 and Example 1 is that the high-pressure homogenization was performed 5 times, and the types and amounts of the components and the preparation method were the same as those in Example 1.

[0058] The difference between Comparative Example 5 and Example 1 is that the shear speed is 1k rpm, and the types and amounts of the components and the preparation method are the same as those in Example 1.

[0059] The difference between Comparative Example 6 and Example 1 is that the shear speed is 5k rpm, and the types and amounts of the components and the preparation method are the same as those in Example 1.

[0060] The test data of Examples 1-3 and Comparative Examples 1-2 are shown in Table 3.

[0061] Table 3 Test data

[0062]

[0063] From Table 3 and Figure 1-3It can be seen that the compositions obtained in Examples 1-3 meet the requirements for dispersion effect, properties, content uniformity, sterilization rate and moisture absorption and moisture retention, and have stable rheological characteristics. As can be seen in Comparative Examples 1-2, increasing the amount of carbomer in Comparative Example 2 will affect the dispersion effect of lidocaine, resulting in unqualified content uniformity; reducing the amount of carbomer in Comparative Example 1 will cause stratification in the finished product, which in turn leads to unqualified sterilization rate. At the same time, the amount of carbomer affects the rheological properties of the finished product, is not within the scope of the present invention, and will lead to instability in the linear viscoelastic region, poor stability at low frequency, and excessive fluctuations in the flow curve. Therefore, the optimal amount of carbomer is 2.5-5.0 mg.

[0064] The test data of Examples 4-7 and Comparative Examples 3-6 are shown in Tables 4 and 5.

[0065] Table 4 Test data

[0066]

[0067]

[0068] Table 5 Test data

[0069]

[0070] From Table 4-5 and Figure 4-9 It can be seen that in Examples 4-7, the dispersion effect, properties, content uniformity, sterilization rate and moisture absorption and moisture retention of the obtained compositions all meet the requirements, and the rheological characteristics are stable. In Comparative Example 4, as the number of high-pressure homogenization increases, the viscosity of the finished product increases exponentially and is unqualified. In Comparative Example 3, the number of high-pressure homogenization decreases, which easily leads to poor dispersion effect and unqualified content uniformity. In Comparative Example 6, as the shear speed increases, the viscosity of the finished product increases exponentially and is unqualified. In Comparative Example 5, the shear speed is reduced at the same time, which easily leads to unqualified content uniformity. Therefore, the optimal number of high-pressure homogenization is 2-4 times, and the optimal shear speed is 2-4krpm.

[0071] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that it is still possible to modify the technical solutions described in the aforementioned embodiments, or to make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A composition containing compound polymyxin B, characterized in that: The composition is mainly prepared from polymyxin B sulfate, neomycin sulfate, bacitracin, lidocaine hydrochloride and carbomer. During its preparation process, carbomer is first dissolved in water and stirred until it is completely swollen to obtain a dispersion liquid, then lidocaine hydrochloride is added and high-pressure homogenization is performed to obtain a suspension, which is then stirred and sheared with polymyxin B sulfate, bacitracin and neomycin sulfate to prepare an ointment, which is then encapsulated to obtain the ointment.

2. The composition containing compound polymyxin B according to claim 1, characterized in that During high-pressure homogenization and dispersion, the high-pressure homogenization pressure is 0.1MPa-0.4MPa, and the number of high-pressure homogenizations is 2-4 times; during stirring and shearing mixing, the shearing speed is 1.5krpm-4.5k rpm, and the shearing time is 10-60min; the particle size D of the lidocaine hydrochloride 90 40-60μm.

3. The composition containing compound polymyxin B according to claim 2, characterized in that Each gram of the composition contains the following components by weight: 4500-6000 units of polymyxin B sulfate, 3150-4200 units of neomycin sulfate, 450-600 units of bacitracin, 36-44 mg of lidocaine hydrochloride and 2.0-5.5 mg of carbomer.

4. The composition containing compound polymyxin B according to claim 3, characterized in that Each gram of the composition contains the following components by weight: 4800-5200 units of polymyxin B sulfate, 3400-3600 units of neomycin sulfate, 480-520 units of bacitracin, 38-42 mg of lidocaine hydrochloride and 2.5-5.0 mg of carbomer.

5. The composition containing compound polymyxin B according to claim 4, characterized in that Each gram of the composition contains the following components by weight: 5000 units of polymyxin B sulfate, 3500 units of neomycin sulfate, 500 units of bacitracin, 40 mg of lidocaine hydrochloride and 4.0 mg of carbomer.

6. The method for preparing the composition containing compound polymyxin B according to claim 1, characterized in that: The steps include: (1) Matrix dispersion: Dissolve carbomer in water and stir until it is completely swollen to obtain a dispersion; (2) Dispersing the active ingredient: adding lidocaine hydrochloride to the dispersion obtained in step (1) and performing high-pressure homogenization to obtain a suspension, wherein the high-pressure homogenization pressure is 0.1 MPa-0.4 MPa and the number of high-pressure homogenization times is 2-4 times; (3) adding polymyxin B sulfate, bacitracin and neomycin sulfate to the suspension obtained in step (2), stirring and shearing to prepare an ointment, the shear speed being 1.5k rpm-4.5k rpm, and the shear time being 10-60 min; (4) Control the temperature of the ointment obtained in step (3) to 40-45° C. and seal it with an ointment tube.

7. The method for preparing the composition containing compound polymyxin B according to claim 6, characterized in that: In step (2), the high-pressure homogenization pressure is 0.2MPa-0.3MPa, preferably 0.3MPa; the particle size D of the lidocaine hydrochloride is 90 40-60μm.

8. The method for preparing the composition containing compound polymyxin B according to claim 7, characterized in that: In step (2), the high-pressure homogenization is performed three times.

9. The method for preparing the composition containing compound polymyxin B according to claim 6, characterized in that: In step (3), the shearing rotation speed is 2k rpm-4k rpm, preferably 3k rpm.

10. The method for preparing the composition containing compound polymyxin B according to claim 6, characterized in that: In step (3), the shearing time is 20-40 min, preferably 30 min.

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