External clindamycin phosphate solution

Abstract

The invention discloses an external clindamycin phosphate solution, which is prepared from the following raw materials in parts by weight: 0.6 to 1.2 parts of clindamycin phosphate, 0.1 to 0.2 part of resveratrol, 0.02 to 0.04 part of glutathione, 0.1 to 0.2 part of xanthan gum, 0.3 to 0.6 part of poloxamer, 25 to 32 parts of glycerol and the balance of water according to the weight of 100 parts. The traditional Chinese medicine composition can be stored for a long time, is good in medicine stability, and can well relieve side effects such as dry skin, sensitive irritation and skin rash.

Description

Technical Field

[0001] The invention relates to a clindamycin phosphate external solution and belongs to the technical field of medicines. Background Art

[0002] Clindamycin phosphate is a clindamycin derivative and a pharmaceutical salt form of clindamycin. It has good antibacterial activity and can inhibit the growth and reproduction of a variety of bacteria. It is commonly used to treat bacterial infections such as respiratory infections, skin and soft tissue infections, and gynecological infections. Common clindamycin phosphate preparations available on the market include topical solutions, gels, liniments, and rubs.

[0003] Clindamycin phosphate topical solution is a topical preparation commonly used in dermatology, mainly used for the treatment of inflammatory acne, and has good antibacterial activity against Propionibacterium acnes; some existing clindamycin phosphate topical solutions have a short storage time and poor stability, and are not effective in relieving side effects such as dry skin, sensitive irritation, and skin rashes. Therefore, the present invention provides a clindamycin phosphate topical solution to solve the problems existing in the prior art. Summary of the invention

[0004] In order to solve at least one problem existing in the above-mentioned prior art, the present invention provides a clindamycin phosphate topical solution, which can be stored for a long time and has good drug stability, and can also effectively alleviate side effects such as dry skin, sensitive irritation, and skin rash.

[0005] In order to achieve the above-mentioned purpose, the present invention adopts the following technical scheme: a clindamycin phosphate external solution, comprising the following raw materials in parts by weight, based on 100 parts by weight: 0.6-1.2 parts of clindamycin phosphate, 0.1-0.2 parts of resveratrol, 0.02-0.04 parts of glutathione, 0.1-0.2 parts of xanthan gum, 0.3-0.6 parts of poloxamer, 25-32 parts of glycerol, and the rest is water.

[0006] Preferably, the mass of the clindamycin phosphate is 4.5 to 7.5 times the mass of resveratrol.

[0007] Preferably, the mass of the clindamycin phosphate is 5 to 6 times the mass of resveratrol.

[0008] Preferably, the mass of the clindamycin phosphate is 5.5 times the mass of resveratrol.

[0009] Preferably, the mass of resveratrol is 4.8 to 6 times the mass of glutathione.

[0010] Preferably, the clindamycin phosphate topical solution comprises the following raw materials in parts by weight: 1.1 parts of clindamycin phosphate, 0.2 parts of resveratrol, 0.04 parts of glutathione, 0.15 parts of xanthan gum, 0.5 parts of poloxamer, 25 parts of glycerol, and 73.01 parts of water.

[0011] Preferably, the clindamycin phosphate topical solution comprises the following raw materials in parts by weight: 0.99 parts of clindamycin phosphate, 0.18 parts of resveratrol, 0.032 parts of glutathione, 0.15 parts of xanthan gum, 0.5 parts of poloxamer, 28 parts of glycerol, and 70.148 parts of water.

[0012] Preferably, the clindamycin phosphate topical solution comprises the following raw materials in parts by weight: 0.66 parts of clindamycin phosphate, 0.12 parts of resveratrol, 0.025 parts of glutathione, 0.15 parts of xanthan gum, 0.45 parts of poloxamer, 28 parts of glycerol, and 70.595 parts of water.

[0013] Preferably, the method for preparing the clindamycin phosphate topical solution comprises the following steps:

[0014] (1) firstly mix water, glycerol and poloxamer and stir evenly to obtain a mixed solution A;

[0015] (2) adding clindamycin phosphate into the mixed solution A and stirring evenly to obtain a mixed solution B;

[0016] (3) Add resveratrol and glutathione to the mixed solution B and mix evenly, then add xanthan gum and mix evenly, and then homogenize to obtain a clindamycin phosphate topical solution.

[0017] Preferably, the homogenization condition is 3500-4500 rpm for 3-5 min.

[0018] The invention has the following beneficial effects: the clindamycin phosphate topical solution of the invention has the characteristics of long-term storage and good drug stability, and the long-term storage can reach 36 months; at the same time, the clindamycin phosphate topical solution of the invention can also well alleviate side effects such as dry skin, sensitive irritation, skin rash, etc.; the glutathione and xanthan gum of the invention cooperate with resveratrol to improve the antioxidant property of the clindamycin phosphate topical solution, promote the stability and long-term storage of the clindamycin phosphate topical solution, and effectively maintain the efficacy of the drug. DETAILED DESCRIPTION

[0019] The following is a clear and complete description of the technical solutions in the implementation of the present invention. The described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in the field without making creative work are within the scope of protection of the present invention. If the specific conditions are not specified in the embodiments, they are carried out according to the normal conditions or the conditions recommended by the manufacturer. If the manufacturer is not specified for the reagents, instruments, and components used, they are all conventional products that can be purchased commercially.

[0020] The invention provides a clindamycin phosphate external solution comprising the following raw materials in parts by weight, based on 100 parts by weight: 0.6-1.2 parts of clindamycin phosphate, 0.1-0.2 parts of resveratrol, 0.02-0.04 parts of glutathione, 0.1-0.2 parts of xanthan gum, 0.3-0.6 parts of poloxamer, 25-32 parts of glycerol, and the remainder being water.

[0021] The present invention also provides a method for preparing a clindamycin phosphate external solution, comprising the following steps:

[0022] (1) firstly mix water, glycerol and poloxamer and stir evenly to obtain a mixed solution A;

[0023] (2) adding clindamycin phosphate into the mixed solution A and stirring evenly to obtain a mixed solution B;

[0024] (3) Add resveratrol and glutathione to the mixed solution B and mix well, then add xanthan gum and mix well, and then homogenize at a speed of 3500-4500 rpm for 3-5 minutes to obtain a clindamycin phosphate topical solution.

[0025] Example

[0026] A clindamycin phosphate topical solution is prepared by weighing raw materials according to Table 1 and by the following method steps:

[0027] (1) firstly mix water, glycerol and poloxamer and stir evenly to obtain a mixed solution A;

[0028] (2) adding clindamycin phosphate into the mixed solution A and stirring evenly to obtain a mixed solution B;

[0029] (3) Resveratrol and glutathione were added to the mixed solution B and stirred evenly, and then xanthan gum was added and mixed evenly, and then homogenized at a speed of 4000 rpm for 4 minutes to obtain a clindamycin phosphate topical solution.

[0030] Table 1

[0031]

[0032]

[0033] Comparative Example

[0034] A clindamycin phosphate topical solution was prepared by weighing the raw materials according to Table 2 and by the following method steps:

[0035] (1) firstly mix water, glycerol and poloxamer and stir evenly to obtain a mixed solution A;

[0036] (2) adding clindamycin phosphate into the mixed solution A and stirring evenly to obtain a mixed solution B;

[0037] (3) Resveratrol and glutathione were added to the mixed solution B and stirred evenly, and then xanthan gum was added and mixed evenly, and then homogenized at a speed of 4000 rpm for 4 minutes to obtain a clindamycin phosphate topical solution.

[0038] Table 2

[0039]

[0040] Effect Example

[0041] 1. Stability test: The clindamycin phosphate external-use solutions prepared in Examples 1 to 15 and Comparative Examples 1 to 4 were packaged in polypropylene bottles and placed under 60° C. and 40% relative humidity conditions. The clindamycin phosphate content (%) and the content of related substances (%) were detected at 0 d, 10 d, and 30 d, respectively. The results are shown in Table 3.

[0042] Table 3 Stability

[0043]

[0044] As can be seen from Table 3, the clindamycin phosphate topical solutions prepared in Examples 1 to 15 of the present invention have a clindamycin phosphate content reduction rate of less than 1% and a related substance content of less than 1% at 60°C and 40% relative humidity for 30 days. It is further found that the formulas of Examples 4, 12 and 15 are better and the drug stability is better. Compared with Example 15, in Comparative Example 1, no resveratrol is added. At 60°C and 40% relative humidity, the clindamycin phosphate content reduction rate is greater than 17% and the related substance content is greater than 2.6% at 60°C and 40% relative humidity for 30 days. In Comparative Example 2, no glutathione is added. At 60°C and 40% relative humidity, the clindamycin phosphate content reduction rate is greater than 17% and the related substance content is greater than 2.6%. Under relative humidity conditions, the reduction rate of clindamycin phosphate content at 30 days was greater than 7%, and the content of related substances was greater than 1.5%; in Comparative Example 3, glycerol was not added, and the reduction rate of clindamycin phosphate content and the content of related substances at 30 days were equivalent to those in Example 15; in Comparative Example 4, xanthan gum was not added, and under the conditions of 60°C and 40% relative humidity, the reduction rate of clindamycin phosphate content at 30 days was slightly greater than 1%, and the content of related substances was less than 5%; This shows that resveratrol and glutathione can synergistically effectively improve the stability of clindamycin phosphate topical solution, and the addition of xanthan gum, resveratrol and glutathione can further improve the stability of the drug.

[0045] 2. Long-term storage test: Based on the stability test, the clindamycin phosphate topical solution prepared in Examples 2 to 4, 6, 10, 13 and 15 and Comparative Examples 1 to 2 and 4 was selected and sealed in a 50 ml spray bottle, and kept in the dark at 30° C. and 60% humidity. After 0 months, 6 months, 12 months, 18 months, 24 months, 30 months and 36 months, it was observed whether the bottle was clear or turbid or precipitated; whether the droplets after the sample was sprayed were uniform. The results are shown in Table 4.

[0046] 2. Long-term storage

[0047]

[0048] As can be seen from Table 4, the clindamycin phosphate topical solutions prepared in Examples 2 to 4 and 15 of the present invention can be stored for up to 36 months without any change in stability, and the clindamycin phosphate topical solutions prepared in Examples 6, 10 and 13 of the present invention can be stored for up to 30 months without any change in stability; compared with Example 15, in Comparative Example 1, no resveratrol was added, and the clindamycin phosphate topical solution became turbid after long-term storage for 12 months; in Comparative Example 2, no glutathione was added, and the clindamycin phosphate topical solution became turbid with a small amount of precipitation after long-term storage for 24 months; in Comparative Example 4, no xanthan gum was added, and the clindamycin phosphate topical solution became slightly turbid after long-term storage for 30 months; this indicates that resveratrol, in collaboration with glutathione and xanthan gum, can effectively improve the long-term storage stability of the clindamycin phosphate topical solution.

[0049] 3. Moisturizing test: The clindamycin phosphate topical solutions prepared in Examples 3, 10, 15 and Comparative Examples 1 to 4 were used to test the moisturizing effect on shaved mice: the skin test area was washed twice with a 1% sodium dodecyl sulfate solution by volume, rinsed with clean water and dried, and the skin moisture value was tested using an Italian skin detector softplus after 30 minutes, that is, no drug was applied, recorded as 0min; then 40 μL of clindamycin phosphate topical solution was evenly applied to the test area skin, that is, the drug was applied, and the skin moisture value was tested every 30 minutes, recorded as 30min, 60min, 90min, and 120min. The results are shown in Table 5.

[0050] Table 5 Moisture retention

[0051]

[0052] As can be seen from Table 5, 120 minutes after applying the medicine, compared with the case without applying the medicine, the skin moisture of Example 3 increased by 80%, the skin moisture of Example 10 increased by 70.1%, the skin moisture of Example 15 increased by 87.1%, the skin moisture of Comparative Example 1 increased by 58.1%, the skin moisture of Comparative Example 2 increased by 63.3%, the skin moisture of Comparative Example 3 increased by 34.4%, and the skin moisture of Comparative Example 4 increased by 63.3%, indicating that resveratrol, glutathione and xanthan gum help to synergize with glycerol to improve the moisturizing effect; the clindamycin phosphate topical solutions prepared in Examples 3, 10 and 15 of the present invention have better moisturizing effect, among which the clindamycin phosphate topical solution of Example 15 has better moisturizing effect.

[0053] 4. Effectiveness test: The clindamycin phosphate topical solutions prepared in the newly prepared Examples 1, 7, 15 and Comparative Examples 1 to 4, as well as Example 7 stored for 24 months, were tested on mice with acne. There were 8 mice with acne in each group. The acne cure rate (cure rate = cure number / total number) and the relief rate of side effects (itchy skin, dryness) during medication (relief rate = relief number / total number) in each group were measured. During the treatment period, the acne site was treated three times a day, 3 to 4 sprays each time, and the course of treatment was 20 days. The results are shown in Table 6.

[0054] Table 6 Validity Experiment

[0055]

[0056] As can be seen from Table 6, Examples 1, 7, the newly prepared clindamycin phosphate topical solution, and the clindamycin phosphate topical solution stored at room temperature and away from light for 30 months in Example 7 all have good therapeutic effects and can relieve skin itching and dryness caused by medication. It can be seen that storage at room temperature for 30 months has no effect on the efficacy. Compared with Example 15, in Comparative Example 1, no resveratrol was added, and in Comparative Example 2, no glutathione was added, and the efficacy of the clindamycin phosphate topical solution was greatly reduced, the cure rate of a 20-day course of treatment was less than 90%, and the relief rate of side effects was less than 90%, and the effect was poor; in Comparative Example 3, no glycerol was added, and the clindamycin phosphate topical solution had good efficacy, but the relief effect on side effects was very poor; in Comparative Example 4, no xanthan gum was added, and the efficacy of the clindamycin phosphate topical solution was affected, the cure rate of a 20-day course of treatment exceeded 95%, but the relief of side effects was less than 90%, and the relief effect was not very good; it indicates that glutathione, xanthan gum and glycerol cooperate with resveratrol to improve the efficacy of the clindamycin phosphate topical solution while helping to improve the relief effect on side effects.

[0057] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the present invention can be implemented in other specific forms without departing from the spirit and essential features of the present invention. Therefore, the embodiments should be considered exemplary and non-restrictive in all respects, and the scope of the present invention is defined by the appended claims rather than the above description, and it is intended that all changes falling within the meaning and scope of the equivalent elements of the claims be included in the present invention.

[0058] In addition, it should be understood that although the present specification is described according to implementation modes, not every implementation mode contains only one independent technical solution. This description of the specification is only for the sake of clarity. Those skilled in the art should regard the specification as a whole. The technical solutions in each embodiment may also be appropriately combined to form other implementation modes that can be understood by those skilled in the art.

Claims

1. A clindamycin phosphate topical solution, characterized in that: The invention comprises the following raw materials in parts by weight, based on 100 parts by weight: 0.6-1.2 parts of clindamycin phosphate, 0.1-0.2 parts of resveratrol, 0.02-0.04 parts of glutathione, 0.1-0.2 parts of xanthan gum, 0.3-0.6 parts of poloxamer, 25-32 parts of glycerol, and the rest is water.

2. A clindamycin phosphate topical solution according to claim 1, characterized in that: The mass of the clindamycin phosphate is 4.5 to 7.5 times that of resveratrol.

3. A clindamycin phosphate topical solution according to claim 2, characterized in that: The mass of the clindamycin phosphate is 5 to 6 times that of resveratrol.

4. A clindamycin phosphate topical solution according to claim 3, characterized in that: The mass of the clindamycin phosphate is 5.5 times that of resveratrol.

5. A clindamycin phosphate external solution according to any one of claims 1 to 4, characterized in that: The mass of the resveratrol is 4.8 to 6 times that of glutathione.

6. A clindamycin phosphate topical solution according to claim 1, characterized in that: The clindamycin phosphate external solution comprises the following raw materials in parts by weight: 1.1 parts of clindamycin phosphate, 0.2 parts of resveratrol, 0.04 parts of glutathione, 0.15 parts of xanthan gum, 0.5 parts of poloxamer, 25 parts of glycerol, and 73.01 parts of water.

7. A clindamycin phosphate topical solution according to claim 1, characterized in that: The clindamycin phosphate external solution comprises the following raw materials in parts by weight: 0.99 parts of clindamycin phosphate, 0.18 parts of resveratrol, 0.032 parts of glutathione, 0.15 parts of xanthan gum, 0.5 parts of poloxamer, 28 parts of glycerol, and 70.148 parts of water.

8. A clindamycin phosphate topical solution according to claim 1, characterized in that: The clindamycin phosphate external solution comprises the following raw materials in parts by weight: 0.66 parts of clindamycin phosphate, 0.12 parts of resveratrol, 0.025 parts of glutathione, 0.15 parts of xanthan gum, 0.45 parts of poloxamer, 28 parts of glycerol, and 70.595 parts of water.

9. A clindamycin phosphate topical solution according to claim 1, characterized in that: The preparation method of the clindamycin phosphate external solution comprises the following steps: (1) firstly mix water, glycerol and poloxamer and stir evenly to obtain a mixed solution A; (2) adding clindamycin phosphate into the mixed solution A and stirring evenly to obtain a mixed solution B; (3) Add resveratrol and glutathione to the mixed solution B and mix evenly, then add xanthan gum and mix evenly, and then homogenize to obtain a clindamycin phosphate topical solution.

10. A clindamycin phosphate topical solution according to claim 9, characterized in that: The homogenization condition is 3500-4500 rpm for 3-5 min.

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