Arbidol hydrochloride emulsifiable paste for inhibiting HSV-2 and preparation method of Arbidol hydrochloride emulsifiable paste

Abstract

The invention provides arbidol hydrochloride emulsifiable paste for inhibiting HSV-2 and a preparation method of the arbidol hydrochloride emulsifiable paste. The hydrochloric acid arbidol emulsifiable paste for inhibiting HSV-2 comprises the following components in percentage by weight: 0.5-2% of micronized hydrochloric acid arbidol; 70%-95% of a cream matrix; 8%-12% of an absorption enhancer; wherein the particle size D90 of the micronized arbidol hydrochloride is less than or equal to 10 microns. The arbidol hydrochloride emulsifiable paste for inhibiting the HSV-2 is provided. According to the arbidol hydrochloride emulsifiable paste for inhibiting HSV-2, the micronized arbidol hydrochloride with the particle size D90 smaller than or equal to 10 microns, the emulsifiable paste matrix and the absorption enhancer are compounded for use, so that the uniformity of the arbidol hydrochloride emulsifiable paste for inhibiting HSV-2 can be improved, and the continuous and stable release speed of the arbidol hydrochloride emulsifiable paste for inhibiting HSV-2 can be ensured; the arbidol hydrochloride emulsifiable paste for inhibiting the HSV-2 has the advantages that the long-term storage performance is stable, and the arbidol hydrochloride emulsifiable paste for inhibiting the HSV-2 is better suitable for treating acute large-area HSV-2.

Description

Technical Field

[0001] The present invention relates to the technical field of arbidol hydrochloride cream, and in particular to an arbidol hydrochloride cream for inhibiting HSV-2 and a preparation method thereof. Background Art

[0002] Abidol hydrochloride is a broad-spectrum antiviral drug, which has a definite antiviral effect on HSV-1. Recent studies have found that Abidol hydrochloride also has an anti-HSV-2 (Herpes Simplex Virus type 2, herpes simplex virus type 2) effect. For example, Chinese patent application No. 201611184528.4 discloses the use of Abidol hydrochloride in the preparation of drugs for the prevention and treatment of anti-type 2 herpes simplex virus, so that Abidol hydrochloride can inhibit the late stage of the HSV-2 replication cycle and play a role by intervening in the virus assembly and release process, and specifically discloses the use of Abidol hydrochloride in the preparation of drugs for the prevention and treatment of anti-type 2 herpes simplex virus, and the dosage form of the drug is pills, tablets, capsules or oral liquids.

[0003] However, most of the arbidol hydrochloride currently available in the market are tablets, capsules, dry suspensions, pills, tablets, oral solutions or injections. The administration methods of the above-mentioned arbidol hydrochloride dosage forms usually cause peak-to-valley fluctuations in the blood drug concentration in the body, resulting in the effective concentration of arbidol hydrochloride in the body being high and low from time to time, thereby affecting the efficacy of arbidol hydrochloride.

[0004] For this reason, a topical administration method of arbidol hydrochloride has appeared on the market. For example, Chinese Patent Application No. 202010184335.9 and Chinese Patent Application No. 202010594075.2 disclose that arbidol hydrochloride can be made into an ointment, but do not involve the specific ingredients and preparation methods of arbidol hydrochloride ointment. In addition, since arbidol hydrochloride in the ointment contains more oily components, the texture is relatively heavy, and the permeability is weak, the drug release rate is slow, resulting in a prolonged treatment time that affects the efficacy, and it is not suitable for the treatment of acute large-area HSV-2. Summary of the invention

[0005] The purpose of the present invention is to overcome the deficiencies in the prior art and provide an arbidol hydrochloride cream for inhibiting HSV-2, which can not only improve the uniformity of the arbidol hydrochloride cream for inhibiting HSV-2, but also ensure the sustained and stable release rate of the arbidol hydrochloride cream for inhibiting HSV-2, so as to enhance the efficacy and reduce the number of medications, and also ensure that the prepared arbidol hydrochloride cream for inhibiting HSV-2 has stable long-term storage performance, so as to better adapt to the treatment of acute large-area HSV-2, and provide an arbidol hydrochloride cream for inhibiting HSV-2 and a preparation method thereof.

[0006] The purpose of this disclosure is achieved through the following technical solutions:

[0007] A kind of arbidol hydrochloride cream used for inhibiting HSV-2 comprises the following components in percentage by weight:

[0008] Micronized arbidol hydrochloride 0.5% to 2%;

[0009] Cream base 70% to 95%;

[0010] Absorption enhancer 8% to 12%;

[0011] Wherein, the particle size of the micronized arbidol hydrochloride is D90≤10 μm.

[0012] In one embodiment, the absorption enhancer includes at least one of propylene carbonate, propylene glycol, isopropyl alcohol and polyethylene glycol.

[0013] In one embodiment, the cream base is a mixture of white beeswax, paraffin, liquid paraffin and white vaseline.

[0014] In one embodiment, in terms of weight percentage, the white beeswax is 4% to 6%, the paraffin is 2% to 4%, the liquid paraffin is 12% to 16%, and the white vaseline is 63% to 69%.

[0015] In one embodiment, the arbidol hydrochloride cream for inhibiting HSV-2 maintains a constant and uniform release rate for 6 hours.

[0016] In one of the embodiments, the droplets of the arbidol hydrochloride cream for inhibiting HSV-2 are ≤25 μm, and the content uniformity RSD of the arbidol hydrochloride cream for inhibiting HSV-2 is 0.1% to 2.0%.

[0017] In one embodiment, the content of the arbidol hydrochloride cream used to inhibit HSV-2 is ≥99.0%.

[0018] A method for preparing an arbidol hydrochloride cream for inhibiting HSV-2 comprises the following steps:

[0019] Micronizing arbidol hydrochloride to obtain micronized arbidol hydrochloride with a particle size of D90≤10 μm;

[0020] The micronized arbidol hydrochloride and the absorption enhancer are first mixed and homogenized to obtain an arbidol hydrochloride solution;

[0021] Performing a second mixing and homogenization on white beeswax, paraffin, liquid paraffin and white vaseline to obtain a cream base liquid;

[0022] The arbidol hydrochloride solution and the cream base solution are mixed and homogenized for the third time to obtain an arbidol hydrochloride emulsion;

[0023] The arbidol hydrochloride emulsion is cooled to obtain the arbidol hydrochloride cream for suppressing HSV-2 in any one of the above-mentioned embodiments.

[0024] In one embodiment, the first mixing and homogenizing conditions are: homogenizing temperature is 70°C to 90°C, homogenizing time is 5min to 15min, homogenizing speed is 5krpm to 10krpm; and / or,

[0025] The second mixing and homogenizing conditions are: homogenizing temperature of 70°C to 90°C, homogenizing time of 5min to 15min, homogenizing speed of 5krpm to 10krpm; and / or,

[0026] The third mixing and homogenizing conditions are: a homogenizing temperature of 70° C. to 90° C., a homogenizing time of 5 min to 15 min, and a homogenizing speed of 5 krpm to 10 krpm.

[0027] In one embodiment, the micronization process is a jet milling operation, wherein the feed pressure of the jet milling operation is 5 bar to 7 bar, the milling pressure is 4 bar to 5 bar, and the feed speed is 2 rpm to 8 rpm.

[0028] Compared with the prior art, the present invention has at least the following advantages:

[0029] 1) Since the added absorption enhancer can improve the permeability of the arbidol hydrochloride cream used to inhibit HSV-2, the release rate of arbidol hydrochloride is increased, so that arbidol hydrochloride can effectively reach the lesion site to inhibit the HSV-2 replication cycle, and enhance the efficacy of arbidol hydrochloride, so as to better adapt to the treatment of acute large-area HSV-2.

[0030] 2) Since the added absorption promoter can directly reduce the difference in the ratio between the micronized arbidol hydrochloride and the cream base, the problem of uneven content of the micronized arbidol hydrochloride caused by sedimentation due to the large difference in density between the micronized arbidol hydrochloride and the cream base is avoided. In particular, when the particle size of the micronized arbidol hydrochloride is D90≤10 μm, the micronized arbidol hydrochloride with a particle size of D90≤10 μm can well overcome the characteristics of poor solubility, easy agglomeration and difficult dispersion of arbidol hydrochloride, further improve the content uniformity of the arbidol hydrochloride cream for inhibiting HSV-2, thereby making the micronized arbidol hydrochloride cream for inhibiting HSV-2 more uniform. The content uniformity RSD of the arbidol hydrochloride cream is 0.1% to 2.0%, which ensures the quality of the arbidol hydrochloride cream for inhibiting HSV-2, and ensures that the prepared arbidol hydrochloride cream for inhibiting HSV-2 can maintain a constant and uniform release rate for 6 hours. In this way, the sustained and stable release rate can not only ensure that the effective HSV-2 inhibition concentration is maintained for a long time, thereby more effectively inhibiting the replication and spread of HSV-2, but also reduce the number of times the user uses the medicine, thereby improving the convenience and comfort of the medicine, and ensuring that the prepared arbidol hydrochloride cream for inhibiting HSV-2 has stable long-term storage performance. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] In order to more clearly illustrate the technical solutions of the embodiments of the present disclosure, the drawings required for use in the embodiments will be briefly introduced below. It should be understood that the following drawings only show certain embodiments of the present disclosure and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other related drawings can be obtained based on these drawings without paying creative work.

[0032] Figure 1 A flow chart of the Arbidol hydrochloride cream for inhibiting HSV-2 according to one embodiment of the present invention;

[0033] Figure 2 It is a linear regression equation diagram of the release rate of the arbidol hydrochloride cream for inhibiting HSV-2 in Examples 1 to 5 of the present invention. DETAILED DESCRIPTION

[0034] In order to facilitate the understanding of the present disclosure, the present disclosure will be described more fully below with reference to the relevant drawings. The preferred embodiments of the present disclosure are given in the drawings. However, the present disclosure can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the disclosure of the present disclosure more thoroughly and comprehensively understood.

[0035] It should be noted that when an element is referred to as being "fixed to" another element, it may be directly on the other element or there may be a central element. When an element is considered to be "connected to" another element, it may be directly connected to the other element or there may be a central element at the same time. The terms "vertical", "horizontal", "left", "right" and similar expressions used herein are for illustrative purposes only and do not represent the only implementation method.

[0036] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art of the present disclosure. The terms used herein in the specification of the present disclosure are only for the purpose of describing specific embodiments and are not intended to limit the present disclosure. The term "and / or" used herein includes any and all combinations of one or more related listed items.

[0037] The present invention discloses an arbidol hydrochloride cream for inhibiting HSV-2, comprising the following components in percentage by weight: 0.5% to 2% of micronized arbidol hydrochloride; 70% to 95% of cream base; 8% to 12% of absorption enhancer; wherein the particle size of the micronized arbidol hydrochloride is D90≤10 μm.

[0038] The above-mentioned arbidol hydrochloride cream for inhibiting HSV-2, because the added absorption promoter can improve the permeability of the arbidol hydrochloride cream for inhibiting HSV-2, improve the release rate of arbidol hydrochloride, so that arbidol hydrochloride can effectively reach the lesion site to inhibit the HSV-2 replication cycle, enhance the efficacy of arbidol hydrochloride, and better adapt to the treatment of acute large-area HSV-2. Furthermore, since the added absorption promoter can directly reduce the difference in the ratio between the micronized arbidol hydrochloride and the cream base, the problem of uneven content of the micronized arbidol hydrochloride caused by sedimentation due to the large difference in density between the micronized arbidol hydrochloride and the cream base is avoided. In particular, when the particle size of the micronized arbidol hydrochloride is D90≤10 μm, the micronized arbidol hydrochloride with a particle size of D90≤10 μm can well overcome the characteristics of poor solubility, easy agglomeration and difficult dispersion of arbidol hydrochloride, further improve the content uniformity of the arbidol hydrochloride cream for inhibiting HSV-2, thereby making the arbidol hydrochloride cream for inhibiting HSV-2 more uniform. The content uniformity RSD of the arbidol hydrochloride cream is 0.1% to 2.0%, which ensures the quality of the arbidol hydrochloride cream for inhibiting HSV-2, and ensures that the prepared arbidol hydrochloride cream for inhibiting HSV-2 can maintain a constant and uniform release rate for 6 hours. In this way, the continuous and stable release rate can not only ensure that the effective inhibition of HSV-2 concentration is maintained for a long time, thereby more effectively inhibiting the replication and spread of HSV-2, but also reduce the number of times users use the medicine, thereby improving the convenience and comfort of the medicine, and ensuring that the prepared arbidol hydrochloride cream for inhibiting HSV-2 has stable long-term storage performance.

[0039] In order to better understand the technical scheme and beneficial effects of the present invention, the present invention is further described in detail below in conjunction with specific embodiments. An arbidol hydrochloride cream for inhibiting HSV-2 in one embodiment includes the following components in percentage by weight: 0.5% to 2% micronized arbidol hydrochloride; 70% to 95% cream base; 8% to 12% absorption enhancer; wherein the particle size of the micronized arbidol hydrochloride is D90≤10μm.

[0040] It can be understood that since the added absorption enhancer can increase the permeability of the arbidol hydrochloride cream used to inhibit HSV-2, and increase the release rate of arbidol hydrochloride, arbidol hydrochloride can effectively reach the lesion site to inhibit the HSV-2 replication cycle, thereby enhancing the efficacy of arbidol hydrochloride to better adapt to the treatment of acute large-area HSV-2.

[0041] It can also be understood that, since the added absorption enhancer can directly reduce the difference in the ratio between the micronized arbidol hydrochloride and the cream matrix, the problem of uneven content of the micronized arbidol hydrochloride caused by sedimentation due to the large difference in density between the micronized arbidol hydrochloride and the cream matrix is ​​avoided, especially with the use of micronized arbidol hydrochloride with a particle size of D90≤10μm, the micronized arbidol hydrochloride with a particle size of D90≤10μm can well overcome the characteristics of poor solubility, easy agglomeration and difficult dispersion of arbidol hydrochloride, further improve the content uniformity of the arbidol hydrochloride cream used to inhibit HSV-2, thereby inhibiting HSV-2. The content uniformity RSD of the arbidol hydrochloride cream used is 0.1% to 2.0%, which ensures the quality of the arbidol hydrochloride cream for inhibiting HSV-2, and ensures that the prepared arbidol hydrochloride cream for inhibiting HSV-2 can maintain a constant and uniform release rate for 6 hours. In this way, the sustained and stable release rate can not only ensure that the effective inhibition of HSV-2 concentration is maintained for a long time, thereby more effectively inhibiting the replication and spread of HSV-2, but also reduce the number of times users use the medicine, thereby improving the convenience and comfort of the medicine, and ensuring that the prepared arbidol hydrochloride cream for inhibiting HSV-2 has stable long-term storage performance.

[0042] In one embodiment, the absorption enhancer includes at least one of propylene carbonate, propylene glycol, isopropyl alcohol and polyethylene glycol to ensure that the added propylene carbonate, propylene glycol, isopropyl alcohol and polyethylene glycol can increase the absorption rate and degree of arbidol hydrochloride in the skin, thereby improving the bioavailability of arbidol hydrochloride, and further ensuring that a highly uniform and relatively stable release rate is prepared.

[0043] It can be understood that although propylene carbonate can promote the penetration of arbidol hydrochloride molecules through the cell membrane of HSV-2, thereby improving the absorption efficiency of the drug, due to the low toxicity of propylene carbonate, if it is used for a long time or in large quantities, it will cause certain toxic effects on the human body, such as skin irritation or damage, and the price of propylene carbonate is relatively expensive. If it is used alone, it will lead to a high preparation cost of the arbidol hydrochloride cream for inhibiting HSV-2; although isopropyl alcohol can promote the penetration of arbidol hydrochloride molecules through the cell membrane, thereby improving the absorption efficiency of the drug, due to the strong volatility of isopropyl alcohol, if it is used alone, it will cause the arbidol hydrochloride cream for inhibiting HSV-2 to evaporate rapidly during storage or use, resulting in unstable concentration of arbidol hydrochloride for inhibiting HSV-2 and poor efficacy, thereby causing users to increase the number of medications. The problem of increasing the efficacy and resulting in a higher usage of the arbidol hydrochloride cream for inhibiting HSV-2; although propylene glycol itself is a penetration enhancer that can enhance the penetration ability of arbidol hydrochloride, so that the arbidol hydrochloride molecules are more likely to contact the lesion skin and penetrate into the deep layer of the lesion skin, thereby increasing the efficacy of the drug, if used alone, for users with cardiovascular disease risks in long-term or acute large-area HSV-2, high concentrations of propylene glycol will aggravate the condition and affect the absorption and utilization of the drug; although polyethylene glycol has the effect of prolonging the release time of arbidol hydrochloride molecules in the body, if used alone, it will cause the release rate of the arbidol hydrochloride cream for inhibiting HSV-2 to slow down, and cannot provide users with a faster release rate, thereby affecting the treatment effect, and cannot be used for the treatment of acute large-area HSV-2.

[0044] Therefore, in the present disclosure, the absorption enhancer is a mixture of propylene carbonate, isopropyl alcohol, propylene glycol and polyethylene glycol, so that the four can play a good synergistic role, thereby satisfying the safety of long-term or acute large-area HSV-2 medication for users with cardiovascular disease risks, and avoiding the problem of high preparation cost caused by the use of propylene carbonate alone. It is also conducive to the preparation of arbidol hydrochloride cream for inhibiting HSV-2 with high uniformity, high content, a relatively fast constant and uniform release rate for 6 hours, and stable storage performance.

[0045] In one embodiment, the weight ratio of propylene carbonate, propylene glycol, isopropanol and polyethylene glycol is 2:2:2:4 to ensure that the four can play a good synergistic role, especially with the use of 4% to 6% white beeswax, 2% to 4% paraffin, 12% to 16% liquid paraffin, and 63% to 69% white vaseline. On the premise of meeting the safety of long-term or acute large-area HSV-2 medication for users with cardiovascular disease risks, it also avoids the problem of high preparation cost caused by the use of propylene carbonate alone, and ensures that the final preparation of arbidol hydrochloride cream for inhibiting HSV-2 has high uniformity, high content, and a relatively fast constant and uniform release rate for 6 hours, and stable storage performance.

[0046] In one embodiment, the cream base is a mixture of white beeswax, paraffin, liquid paraffin and white vaseline. Specifically, in one embodiment, the white beeswax is 4% to 6%, the paraffin is 2% to 4%, the liquid paraffin is 12% to 16%, and the white vaseline is 63% to 69%, so as to ensure that the white beeswax, paraffin, liquid paraffin and white vaseline can play a good synergistic role, so as to provide a stable cream base for arbidol hydrochloride, which is beneficial to the arbidol hydrochloride cream for inhibiting HSV-2 to act evenly on the affected skin, especially with the use of a mixture of propylene carbonate, isopropyl alcohol and polyethylene glycol as an absorption promoter, while satisfying the safety of long-term or acute large-area HSV-2 medication for users with cardiovascular disease risks, it also avoids the problem of high preparation cost caused by the use of propylene carbonate alone, and also ensures that the preparation of arbidol hydrochloride cream for inhibiting HSV-2 with high uniformity, high content, and a relatively fast constant and uniform release rate for 6 hours, and stable storage performance is obtained.

[0047] It should be noted that, although the content uniformity of the arbidol hydrochloride cream for inhibiting HSV-2 can be effectively improved by reducing the particle size of the micronized arbidol hydrochloride, so as to ensure that the prepared arbidol hydrochloride cream for inhibiting HSV-2 can maintain a constant and uniform release rate for 6 hours, the specific surface area of ​​the micronized arbidol hydrochloride with small particle size is relatively large, resulting in its high hygroscopicity, thereby affecting the stability of the arbidol hydrochloride cream for inhibiting HSV-2. Therefore, in the present disclosure, when 4% to 6% of white beeswax, 2% to 4% of the paraffin, 12% to 16% of the liquid paraffin, 63% to 69% of the white vaseline, and the propylene carbonate, propylene glycol, isopropyl alcohol, and polyethylene glycol are used in a weight ratio of 2:2:2:4, the small-particle-size micronized arbidol hydrochloride can be evenly dispersed in the protective film system of white beeswax, paraffin, liquid paraffin, white vaseline, propylene carbonate, propylene glycol, isopropyl alcohol, and polyethylene glycol, which helps to form a hydrochloric acid for inhibiting HSV-2. The droplets of Abidor Cream are ≤25μm. In this way, while improving the long-term storage stability of Abidor Hydrochloride Cream for inhibiting HSV-2, it also improves the safety of long-term or acute large-area HSV-2 medication for users at risk of cardiovascular disease, and avoids the problem of high preparation cost caused by the use of propylene carbonate alone, so as to ensure that the final Abidor Hydrochloride Cream for inhibiting HSV-2 with high uniformity, high content, a relatively fast constant and uniform release rate for 6 hours, and stable storage performance can be prepared.

[0048] It can also be understood that the protective film system of small-particle micronized arbidol hydrochloride, white beeswax, paraffin, liquid paraffin, white vaseline, propylene carbonate, propylene glycol, isopropyl alcohol and polyethylene glycol is a multilayer structure with stable structure, propylene glycol, polyethylene glycol and micronized arbidol hydrochloride are combined to form an inner layer, white beeswax, paraffin, liquid paraffin and white vaseline are the middle layer, and are combined with micronized arbidol hydrochloride, propylene glycol and polyethylene glycol to form a stable structure, and propylene carbonate and isopropyl alcohol are the outer layer. , and combined with white beeswax, paraffin, liquid paraffin, and white vaseline to form a stable structure to ensure that the formed protective film system is a structurally stable multi-layer structure. In this way, while improving the long-term storage stability of the arbidol hydrochloride cream for inhibiting HSV-2, it is also ensured that the prepared arbidol hydrochloride cream for inhibiting HSV-2 has high uniformity, high content, and maintains a relatively fast constant and uniform release rate within 6 hours, so as to be better suitable for the application of acute large-area HSV-2.

[0049] It can be understood that if the droplets of the arbidol hydrochloride cream used to inhibit HSV-2 are larger than 25 μm, the larger droplets cannot be evenly distributed on the affected skin, which will not only reduce the absorption efficiency of arbidol hydrochloride, but also reduce the treatment effect: and droplets larger than 25 μm will cause arbidol hydrochloride to be unable to effectively penetrate into the deep layers of the affected skin, thereby reducing the inhibitory effect on HSV-2; and larger droplets are more difficult to apply and are prone to slipping, resulting in waste during use. Therefore, in one of the embodiments, the droplets of the arbidol hydrochloride cream for inhibiting HSV-2 are ≤25 μm, so as to ensure that the droplets of the arbidol hydrochloride cream for inhibiting HSV-2 smaller than 25 μm can be evenly distributed on the affected skin, thereby improving the absorption efficiency of arbidol hydrochloride; and the droplets of the arbidol hydrochloride cream for inhibiting HSV-2 smaller than 25 μm can penetrate well into the deep layer of the affected skin, thereby reducing the inhibitory effect on HSV-2; and the droplets of the arbidol hydrochloride cream for inhibiting HSV-2 smaller than 25 μm are not easy to slip, thereby reducing the waste during use, and reducing the problem of reduced comfort of the user in taking the medicine due to greater irritation to the affected skin caused by excessive droplet size.

[0050] In one embodiment, the content uniformity RSD of the arbidol hydrochloride cream for inhibiting HSV-2 is 0.1% to 2.0%, especially when used in conjunction with the content of the arbidol hydrochloride cream for inhibiting HSV-2 of ≥99.0%, to ensure that the arbidol hydrochloride cream for inhibiting HSV-2 has high content uniformity and high content, can ensure that the drug concentration in different lesion sites remains consistent, which helps the arbidol hydrochloride cream for inhibiting HSV-2 to better inhibit the replication and spread of the HSV-2 virus.

[0051] The present disclosure also provides a method for preparing an arbidol hydrochloride cream for inhibiting HSV-2, comprising the following steps: first, micronizing the arbidol hydrochloride to obtain micronized arbidol hydrochloride with a particle size of D90≤10 μm; then, performing a first mixing and homogenizing of the micronized arbidol hydrochloride and an absorption enhancer to obtain an arbidol hydrochloride solution; followed by a second mixing and homogenizing of white beeswax, paraffin, liquid paraffin and white vaseline to obtain a cream base liquid; then, performing a third mixing and homogenizing of the arbidol hydrochloride solution and the cream base liquid to obtain an arbidol hydrochloride emulsion; finally, cooling the arbidol hydrochloride emulsion to obtain the arbidol hydrochloride cream for inhibiting HSV-2 in any of the above embodiments.

[0052] In order to better understand the technical solutions and beneficial effects of the present invention, the present invention is further described in detail below in conjunction with specific embodiments. Figure 1As shown, the preparation method of the arbidol hydrochloride cream for inhibiting HSV-2 of one embodiment comprises part or all of the following steps:

[0053] S101, micronizing arbidol hydrochloride to obtain micronized arbidol hydrochloride with a particle size of D90≤10 μm for later use.

[0054] It can be understood that if the feed pressure of the airflow milling operation is less than 5 bar, the milling efficiency will be low. If the feed pressure is greater than 7 bar, the impact force of the arbidol hydrochloride raw material on the milling chamber and the conveying pipeline will cause the arbidol hydrochloride raw material to generate heat and decompose. In addition, excessive impact pressure will also cause the airflow mill to wear. If the milling pressure is less than 4 bar, the arbidol hydrochloride raw material will not be sufficiently milled, and micronized arbidol hydrochloride particles with uniform particle size cannot be prepared. If the milling pressure is greater than 5 bar, the arbidol hydrochloride raw material will not be sufficiently milled. When the feed speed is greater than ar, the friction and collision between the arbidol hydrochloride raw material and the wall of the grinding chamber will become more intense, causing the arbidol hydrochloride raw material to generate more heat and lead to the decomposition of the arbidol hydrochloride raw material; if the feed speed is less than 2rpm, the amount of arbidol hydrochloride raw material entering the grinding chamber per unit time is small, resulting in low space utilization in the grinding chamber; if the feed speed is greater than 8rpm, the residence time of the arbidol hydrochloride raw material in the grinding chamber is insufficient, and micronized arbidol hydrochloride particles with relatively uniform particle size cannot be prepared.

[0055] It is worth mentioning that during the airflow crushing operation, the solid arbidol hydrochloride raw material will have a large collision and friction with the inner wall of the crushing chamber, which will cause the arbidol hydrochloride raw material to heat up itself. When arbidol hydrochloride is at 90.02°C, the weaker chemical bonds such as hydrogen bonds in the structure of arbidol hydrochloride will break, resulting in the first weightless decomposition of arbidol hydrochloride, which is the degradation of arbidol hydrochloride, thereby affecting the pharmacological function of arbidol hydrochloride.

[0056] Therefore, in the present disclosure, by effectively controlling the conditions of the micronization treatment, specifically, the micronization treatment is an airflow pulverization operation, the feed pressure of the airflow pulverization operation is 5bar~7bar, the pulverization pressure is 4bar~5bar, and the feed speed is 2rpm~8rpm, so as to ensure that the feed pressure, pulverization pressure and feed speed of the arbidol hydrochloride raw material are more suitable, thereby ensuring that the arbidol hydrochloride raw material is not prone to degradation during the pulverization process, and also improving the space utilization rate in the pulverization chamber to achieve large-scale micronization of the arbidol hydrochloride raw material, thereby ensuring the preparation of micronized arbidol hydrochloride particles with uniform particle size D90≤10μm, and also reducing the probability of wear of the airflow pulverizer during the pulverization process, thereby improving the service life of the airflow pulverizer.

[0057] In one embodiment, the raw material of Abidor Hydrochloride is provided by Shijiazhuang Zhongshuo Pharmaceutical Co., Ltd. to ensure batch preparation of micronized Abidor Hydrochloride with a particle size D90 of 5.22 μm, D50 of 1.52 μm, and D10 of 0.20 μm.

[0058] In a preferred embodiment, when the absorption promoter is a mixture of propylene carbonate, propylene glycol, isopropyl alcohol and polyethylene glycol, propylene glycol and polyethylene glycol are first added for homogeneous mixing, and then isopropyl alcohol and propylene carbonate are added for mixing again to ensure that the added propylene glycol and polyethylene glycol can be fully combined with the micronized arbidol hydrochloride to form a structurally stable inner layer; and the isopropyl alcohol and propylene carbonate added later can be placed on the outside of the inner layer, which is conducive to combining with the subsequent white beeswax, paraffin, liquid paraffin, and white vaseline, thereby forming a structurally stable and non-stratified arbidol hydrochloride emulsion, thereby ensuring the long-term storage stability of the arbidol hydrochloride emulsion, the uniformity RSD is 0.1% to 2.0%, the arbidol hydrochloride content is ≥99.0%, the release rate is maintained at a constant and uniform rate for 6 hours, and the comfort of medication is ensured.

[0059] like Figure 2 As shown, in one embodiment, the arbidol hydrochloride cream used to inhibit HSV-2 is released at a constant rate and uniformly according to the linear regression equation of y=ax+b, wherein y is the cumulative release amount of arbidol hydrochloride per unit area, a is (0.1916-0.2067), x is the release time h, and b is (0.1822-0.2024).

[0060] S102, performing a first mixing and homogenizing of the micronized arbidol hydrochloride and the absorption enhancer to obtain an arbidol hydrochloride solution, so as to ensure that the micronized arbidol hydrochloride can be evenly dispersed in the absorption enhancer.

[0061] It can be understood that if the homogenization temperature is too high or the homogenization time is too long, the active ingredients of the micronized arbidol hydrochloride will be affected. If the homogenization temperature is too low or the homogenization time is too short, a uniform and stable arbidol hydrochloride solution cannot be prepared. If the homogenization speed is too fast, too much heat will be generated to affect the active ingredients of the micronized arbidol hydrochloride. If the homogenization speed is too slow, a uniform and stable arbidol hydrochloride solution cannot be obtained. Therefore, in one embodiment, the first mixing and homogenizing conditions are: the homogenization temperature is 70°C to 90°C, the homogenization time is 5min to 15min; the homogenization speed is 5krpm to 10krpm, so as to avoid excessive shear heat during the homogenization process, which causes the degradation of the micronized arbidol hydrochloride and affects the effective ingredients of the micronized arbidol hydrochloride, thereby ensuring that the effective ingredients of the micronized arbidol hydrochloride with a small and uniform particle size and high effective ingredients are prepared, so as to ensure that the content of the prepared arbidol hydrochloride cream for inhibiting HSV-2 is ≥99.0%, and the content of the arbidol hydrochloride cream for inhibiting HSV-2 is uniform. The uniformity RSD is 0.1% to 2.0%, so as to achieve a constant and uniform release rate of the arbidol hydrochloride cream for inhibiting HSV-2 for 6 hours, thereby enhancing the efficacy of the arbidol hydrochloride cream for inhibiting HSV-2, and helping to prepare the arbidol hydrochloride cream for inhibiting HSV-2 with droplets ≤25μm, so that the arbidol hydrochloride cream for inhibiting HSV-2 with droplets ≤25μm can meet the requirements of good permeability while reducing the irritation of large-sized droplets to the lesion skin, thereby improving the user's comfort when taking the medicine, and is also conducive to the preparation of the arbidol hydrochloride cream for inhibiting HSV-2 with stable storage performance.

[0062] In a preferred embodiment, the first mixing and homogenizing conditions are: a homogenizing temperature of 70° C. to 80° C., a homogenizing time of 5 min to 15 min, and a homogenizing speed of 5 krpm to 7 krpm.

[0063] In one of the embodiments, the micronized arbidol hydrochloride and the absorption enhancer are mixed under heating at 70°C to 80°C, and then homogenized at a homogenization speed of 5krpm to 7krpm for 5min to 10min, thereby achieving the first mixing and homogenizing operation of the micronized arbidol hydrochloride and the absorption enhancer.

[0064] S103, performing a second mixing and homogenization on white beeswax, paraffin, liquid paraffin and white vaseline to obtain a cream base liquid, so as to ensure that a cream base liquid with a small and uniform particle size is obtained. On the one hand, it is convenient to quickly and evenly mix with the arbidol hydrochloride solution of S102, thereby reducing the influence of subsequent shear heat on the active ingredients of arbidol hydrochloride. On the other hand, it is conducive to the subsequent preparation of a uniformly dispersed arbidol hydrochloride cream for inhibiting HSV-2 with droplets ≤25μm.

[0065] In one embodiment, the second mixing and homogenizing conditions are: the homogenizing temperature is 70°C to 90°C, the homogenizing time is 5min to 15min, and the homogenizing speed is 5krpm to 10krpm, so as to ensure a uniform and stable cream base liquid with a small particle size.

[0066] In one embodiment, liquid paraffin, white beeswax, paraffin and white vaseline are mixed, then heated to melt at 70°C to 90°C, and homogenized at a speed of 5krpm to 10krpm for 5min to 15min to complete the second mixing and homogenization of white beeswax, paraffin, liquid paraffin and white vaseline.

[0067] S104. Perform a third mixing and homogenization on the arbidol hydrochloride solution and the cream base liquid to obtain an arbidol hydrochloride emulsion; the conditions of the third mixing and homogenization are: a homogenization temperature of 70°C to 90°C, a homogenization time of 5min to 15min, and a homogenization speed of 5krpm to 10krpm, so as to prepare an arbidol hydrochloride cream for inhibiting HSV-2 with a uniformity RSD of 0.1% to 2.0%, droplets ≤25μm, stable storage performance, an arbidol hydrochloride content ≥99.0%, and a constant and uniform release rate maintained for 6 hours.

[0068] In one embodiment, the arbidol hydrochloride solution and the cream base liquid are mixed under heating at 70°C to 90°C, and then homogenized at a speed of 5krpm to 10krpm for 5min to 15min to complete the third mixing and homogenization of the arbidol hydrochloride solution and the cream base liquid.

[0069] S105, cooling the Arbidol hydrochloride emulsion to obtain the Arbidol hydrochloride cream for inhibiting HSV-2 in any of the above embodiments. Specifically, the cooling temperature is 25°C to 30°C, and the cooling time is 40min to 60min.

[0070] The preparation method of the above-mentioned arbidol hydrochloride cream for inhibiting HSV-2 comprises the following steps: firstly mixing and homogenizing micronized arbidol hydrochloride and an absorption promoter to obtain an arbidol hydrochloride solution, and then performing a second mixing and homogenizing on white beeswax, paraffin, liquid paraffin and white vaseline to obtain an cream base liquid, thereby achieving step-by-step mixing and homogenizing of the arbidol hydrochloride solution and the cream base liquid, effectively avoiding the problem of increased loss of the active ingredients of arbidol hydrochloride due to the prolonged homogenization time of arbidol hydrochloride, and coordinating with the use of the third mixing and homogenizing to ensure that the arbidol hydrochloride cream for inhibiting HSV-2 with a uniformity RSD of 0.1% to 2.0%, droplets ≤25 μm, stable storage performance, arbidol hydrochloride content ≥99.0%, and a constant and uniform release rate maintained for 6 hours is prepared, so as to be better suitable for the application of acute large-area HSV-2.

[0071] Compared with the prior art, the present invention has at least the following advantages:

[0072] 1) Since the added absorption enhancer can improve the permeability of the arbidol hydrochloride cream used to inhibit HSV-2, the release rate of arbidol hydrochloride is increased, so that arbidol hydrochloride can effectively reach the lesion site to inhibit the HSV-2 replication cycle, and enhance the efficacy of arbidol hydrochloride, so as to better adapt to the treatment of acute large-area HSV-2.

[0073] 2) Since the added absorption promoter can directly reduce the difference in the ratio between the micronized arbidol hydrochloride and the cream base, the problem of uneven content of the micronized arbidol hydrochloride caused by sedimentation due to the large difference in density between the micronized arbidol hydrochloride and the cream base is avoided. In particular, when the particle size of the micronized arbidol hydrochloride is D90≤10 μm, the micronized arbidol hydrochloride with a particle size of D90≤10 μm can well overcome the characteristics of poor solubility, easy agglomeration and difficult dispersion of arbidol hydrochloride, further improve the content uniformity of the arbidol hydrochloride cream for inhibiting HSV-2, thereby making the micronized arbidol hydrochloride cream for inhibiting HSV-2 more uniform. The content uniformity RSD of the arbidol hydrochloride cream is 0.1% to 2.0%, which ensures the quality of the arbidol hydrochloride cream for inhibiting HSV-2, and ensures that the prepared arbidol hydrochloride cream for inhibiting HSV-2 can maintain a constant and uniform release rate for 6 hours. In this way, the sustained and stable release rate can not only ensure that the effective HSV-2 inhibition concentration is maintained for a long time, thereby more effectively inhibiting the replication and spread of HSV-2, but also reduce the number of times the user uses the medicine, thereby improving the convenience and comfort of the medicine, and ensuring that the prepared arbidol hydrochloride cream for inhibiting HSV-2 has stable long-term storage performance.

[0074] Compared with the prior art, the present invention has at least the following advantages:

[0075] Some specific examples are given below, and if % is mentioned, it means percentage by weight. It should be noted that the following examples do not exhaust all possible situations, and the materials used in the following examples can be obtained from commercial sources unless otherwise specified.

[0076] Among them, Abidol hydrochloride was provided by Shijiazhuang Zhongshuo Pharmaceutical Co., Ltd., and other reagents or instruments used without indicating the manufacturer were conventional products that could be purchased commercially.

[0077] Table 1 Recipe

[0078]

[0079] Table 2 Homogenization process parameters

[0080]

[0081]

[0082] Examples 1 to 5 and Comparative Examples 1 to 7 were prepared according to the formulations in Table 1 and the homogenization process parameters in Table 2, including the following steps:

[0083] S101, micronizing arbidol hydrochloride to obtain micronized arbidol hydrochloride with a particle size of D90≤10 μm, wherein the arbidol hydrochloride raw material is subjected to airflow pulverization operation using an airflow pulverizer, with a feed pressure of 7 bar, a pulverization pressure of 5 bar, and a feed speed of 5 rpm to obtain micronized arbidol hydrochloride particles with a particle size of D90≤10 μm;

[0084] S102, mixing the micronized arbidol hydrochloride and the absorption enhancer at the homogenization temperature corresponding to Table 2, and then homogenizing at the homogenization speed corresponding to Table 2 for a corresponding time to obtain an arbidol hydrochloride solution,

[0085] S103, white beeswax, paraffin, liquid paraffin and white vaseline are mixed, and then heated to melt at a homogenization temperature corresponding to Table 2, and then homogenized at a homogenization speed corresponding to Table 2 for a corresponding time to obtain an cream base liquid;

[0086] S104, mixing the arbidol hydrochloride solution and the cream base solution at the homogenization temperature corresponding to Table 2, and then homogenizing at the homogenization speed corresponding to Table 2 for a corresponding time to obtain an arbidol hydrochloride emulsion;

[0087] S105, cooling the arbidol hydrochloride emulsion at 25° C. for 40 min to obtain an arbidol hydrochloride cream for inhibiting HSV-2.

[0088] It is worth mentioning that when multiple absorption enhancers are used in Example 5, there is a requirement for the order of addition in step S102: first add propylene glycol and polyethylene glycol and homogenize for 5 minutes, then add isopropanol and propylene carbonate and homogenize for 10 minutes, and the rest remain unchanged.

[0089] Comparative Example 8

[0090] The difference from Example 1 is that the "feeding pressure 7 bar, crushing pressure 5 bar, feeding speed 5 rpm" in step S101 is replaced by "feeding pressure 7 bar, crushing pressure 3 bar, feeding speed 5 rpm", and the rest remains unchanged.

[0091] Comparative Example 9

[0092] The difference from Example 1 is that the "feeding pressure 7 bar, crushing pressure 5 bar, feeding speed 5 rpm" in step S101 is replaced by "feeding pressure 7 bar, crushing pressure 6 bar, feeding speed 5 rpm", and the rest remains unchanged.

[0093] The appearance of the Arbidol hydrochloride cream for inhibiting HSV-2 obtained in the above Examples 1 to 5 and Comparative Examples 1 to 9 was tested to obtain the experimental data in Table 3:

[0094] Table 3

[0095]

[0096]

[0097] As can be seen from the above table 3, since embodiments 1 to 5 use an absorption promoter and the cream base uses a mixture of white beeswax, paraffin, liquid paraffin and white vaseline, and the D90 of micronized arbidol hydrochloride is ≤10 μm, especially with a homogenization temperature of 70 ℃ to 90 ℃, the homogenization time is 5min to 15min; the homogenization speed is the use of the first mixed homogenization of 5krpm to 10krpm and the second mixed homogenization, to ensure that the content of arbidol hydrochloride prepared is ≥99.0%, and the content uniformity RSD of arbidol hydrochloride is 0.1% to 2.0%, indicating that the arbidol hydrochloride cream for suppressing HSV-2 prepared by embodiments 1 to 5 has a good uniformity. Wherein, embodiment 3 and embodiment 5 comprehensive indicators are better.

[0098] From the comparison between Example 1 and Comparative Example 9, it can be seen that due to the large crushing pressure of Comparative Example 9, the thermal degradation of Abidol Hydrochloride is more serious, resulting in a low content in Comparative Example 9.

[0099] The arbidol hydrochloride cream for inhibiting HSV-2 of Examples 1 to 5 and Comparative Examples 1 to 9 was subjected to particle size detection and loading detection to obtain the experimental data of Table 4:

[0100] Among them, take one sample, place the contents on a glass slide and spread them into a thin layer. The area of ​​the thin layer is equivalent to the area of ​​the cover glass. Spread three slides in total and measure the particle size and particle size distribution according to the method for determination (Method 1, General Rules 0982 of the 2020 edition of the Chinese Pharmacopoeia);

[0101] Filling quantity test: Take 5 samples from each group according to the minimum filling quantity inspection method (General Rule 0942 of the 2020 edition of the Chinese Pharmacopoeia), remove the outer cover and label, clean the outer wall of the container with purified water and dry it, accurately weigh the weight, remove the contents, wash the container with a suitable solvent and dry it, and then accurately weigh the weight of the empty container;

[0102] Content weight (g) = total weight - container weight

[0103] Filling volume (%) = content weight ÷ labeled amount (10.0g) × 100%

[0104] Table 4

[0105]

[0106]

[0107] Examples 1 to 5 in Table 4 above all meet the standards of General Chapter 0942 of the 2020 edition of the Chinese Pharmacopoeia, that is, not less than 93% of the labeled capacity.

[0108] Furthermore, it can be seen from Example 1 and Comparative Example 4 in Table 4 above that since Comparative Example 4 lacks white vaseline, the content index of Comparative Example 4 is lower than 10.

[0109] Further, it can be seen from Example 1 and Comparative Examples 8 to 9 in Table 4 above that due to the relatively small crushing pressure of 3 bar in Comparative Example 8, the particle size of the micronized arbidol hydrochloride is relatively large, resulting in the content index of Comparative Example 8 being lower than 10. Among them, the content indexes of Examples 2, 4, 5 and Comparative Example 2 are better.

[0110] The content (n=6), droplet size, and droplet distribution of the Abidol hydrochloride cream for inhibiting HSV-2 obtained in the above Examples 1 to 5 and Comparative Examples 1, 2, 3, 4, 8, and 9 were tested to obtain the experimental data in Table 5:

[0111] Among them, the method of content determination is:

[0112] 1) Test solution: Take an appropriate amount of the product (equivalent to about 20 mg of arbidol hydrochloride), accurately weigh it, put it in a beaker, add about 30 ml of anhydrous ethanol, heat it in a water bath to dissolve it, then cool it in an ice bath, filter it, put the filtrate in a 100 ml volumetric flask, extract it three times in the same way, add the filtrate into the volumetric flask, let it reach room temperature, dilute it to the scale with anhydrous ethanol, and shake it well.

[0113] 2) Reference solution: Accurately weigh an appropriate amount of Abidor Hydrochloride reference substance, add an appropriate amount of ethanol, sonicate to dissolve, and quantitatively dilute to make a solution containing approximately 10 μg per 1 ml.

[0114] 3) Determination method: According to the UV-visible spectrophotometry, the absorbance was measured at a wavelength of 257 nm;

[0115] Table 5

[0116] Serial number content / % Content RSD / % Droplet size Droplet distribution Example 1 100.0 0.3 ≤25μm Uniform Example 2 100.1 1.0 ≤25μm Uniform Example 3 99.9 0.3 ≤25μm Uniform Example 4 100.2 0.6 ≤25μm Uniform Example 5 100.0 0.3 ≤25μm Uniform Comparative Example 1 99.3 2.5 ≤25μm Uneven Comparative Example 2 100.1 2.1 ≤25μm Uneven Comparative Example 3 100.6 2.8 ≤25μm Uneven Comparative Example 4 100.7 2.2 ≤25μm Uneven Comparative Example 8 100.6 0.5 >25μm Uniform Comparative Example 9 97.6 0.7 ≤25μm Uniform

[0117] As can be seen from Table 5 above, the use of micronized arbidol hydrochloride with D90 ≤ 10 μm, a homogenization temperature of 70°C to 90°C, a homogenization time of 5 min to 15 min, and a homogenization speed of 5 krpm to 10 krpm, is conducive to the preparation of a uniform and stable arbidol hydrochloride cream for inhibiting HSV-2 with a droplet size of ≤ 25 μm.

[0118] The Arbidol hydrochloride cream for inhibiting HSV-2 obtained in Examples 1 to 5 above was subjected to in vitro release to obtain the experimental data in Table 6:

[0119] Franz transdermal diffusion cell was used for transdermal test. When using, the skin was fixed on the diffusion cell and an appropriate amount of sample was applied. The transdermal area was 2.8±0.1cm2, the water bath temperature was 35℃, the stirring speed was 300rpm, the receiving cell volume was 6ml, and the receiving solution was 0.9% saline solution. Samples were taken at 0.5, 1, 2, 4, and 6h, 200μl each time, and an equal volume of 35℃ saline was immediately added. The samples were analyzed by high performance liquid chromatography.

[0120] Receiving liquid treatment method: Take 200 μl of the receiving liquid and place it in a centrifuge tube, add 200 μl of mobile phase, oscillate for 2 minutes, centrifuge at 10,000 rpm for 10 minutes, and take 20 μl of the supernatant for injection detection.

[0121] Table 6

[0122]

[0123] It can be seen from Table 6 above that the active ingredient arbidol hydrochloride in the arbidol hydrochloride cream for inhibiting HSV-2 prepared in Examples 1 to 5 can penetrate the skin of miniature pigs and can always maintain a nearly constant and uniform release rate during the test lasting 6 hours.

[0124] Furthermore, the slope of the linear regression equation of the release rate of the arbidol hydrochloride cream for inhibiting HSV-2 prepared in Examples 1 to 5 is in the range of 0.1916 to 0.2067, R 2 It is 0.9862-0.9884, and the linear regression equation is y=ax+b, wherein y is the cumulative release amount of arbidol hydrochloride per unit area, a is (0.1916-0.2067), x is the release time h, and b is (0.1822-0.2024).

[0125] The stability of the Arbidol hydrochloride cream for inhibiting HSV-2 obtained in Examples 1 to 5 above was studied to obtain the experimental data in Tables 7 and 8:

[0126] (1) Influencing factor test

[0127] The samples were subjected to stress testing at 50 °C, 2 - 8 °C and under light conditions. The results showed that the Arbidol Hydrochloride Cream for inhibiting HSV-2 prepared according to the formulations and processes of the present disclosure in Examples 1 - 5 had stable properties.

[0128] Table 7

[0129]

[0130]

[0131]

[0132] (2) Accelerated, long-term and low-temperature cycle tests

[0133] The samples were subjected to stability studies under accelerated, long-term and low-temperature test conditions. The results showed that the Arbidol Hydrochloride Cream for inhibiting HSV-2 prepared according to the formulations and processes of the present disclosure in Examples 1 - 5 had stable properties.

[0134] Table 8

[0135]

[0136]

[0137] Among them, *Low-temperature test: three cycles. Each cycle of the low-temperature test is to place at 2 - 8 °C for 2 days first, and then at 40 °C for 2 days.

[0138] The above-described embodiments merely represent several implementation manners of the present disclosure. The description is relatively specific and detailed, but it should not be construed as a limitation on the scope of the disclosed patent. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present disclosure, several modifications and improvements can still be made, and these all belong to the protection scope of the present disclosure. Therefore, the protection scope of the present disclosure patent shall be subject to the appended claims.

Claims

1. A arbidol hydrochloride cream for inhibiting HSV-2, characterized in that: The weight percentages of the following components are included: Micronized arbidol hydrochloride 0.5% to 2%; Cream base 70% to 95%; Absorption enhancer 8% to 12%; Wherein, the particle size of the micronized arbidol hydrochloride is D90≤10 μm.

2. The arbidol hydrochloride cream for suppressing HSV-2 according to claim 1, characterized in that, The absorption enhancer includes at least one of propylene carbonate, propylene glycol, isopropyl alcohol and polyethylene glycol.

3. The arbidol hydrochloride cream for suppressing HSV-2 according to claim 1, characterized in that, The cream base is a mixture of white beeswax, paraffin, liquid paraffin and white vaseline.

4. The arbidol hydrochloride cream for suppressing HSV-2 according to claim 3, characterized in that, In terms of weight percentage, the white beeswax is 4% to 6%, the paraffin is 2% to 4%, the liquid paraffin is 12% to 16%, and the white vaseline is 63% to 69%.

5. The arbidol hydrochloride cream for suppressing HSV-2 according to claim 1, characterized in that, The arbidol hydrochloride cream for inhibiting HSV-2 maintains a constant and uniform release rate for 6 hours.

6. The arbidol hydrochloride cream for suppressing HSV-2 according to claim 1, characterized in that, The droplets of the arbidol hydrochloride cream for inhibiting HSV-2 are ≤25 μm, and the content uniformity RSD of the arbidol hydrochloride cream for inhibiting HSV-2 is 0.1% to 2.0%.

7. The arbidol hydrochloride cream for suppressing HSV-2 according to claim 1, characterized in that, The content of the arbidol hydrochloride cream used for inhibiting HSV-2 is ≥99.0%.

8. A method for preparing an arbidol hydrochloride cream for inhibiting HSV-2, characterized in that: The steps include: Micronizing arbidol hydrochloride to obtain micronized arbidol hydrochloride with a particle size of D90≤10 μm; The micronized arbidol hydrochloride and the absorption enhancer are first mixed and homogenized to obtain an arbidol hydrochloride solution; Performing a second mixing and homogenization on white beeswax, paraffin, liquid paraffin and white vaseline to obtain a cream base liquid; The arbidol hydrochloride solution and the cream base solution are mixed and homogenized for the third time to obtain an arbidol hydrochloride emulsion; The arbidol hydrochloride emulsion is cooled to obtain the arbidol hydrochloride cream according to any one of claims 1 to 7.

9. The method for preparing the arbidol hydrochloride cream for suppressing HSV-2 according to claim 8, wherein: The first mixing and homogenizing conditions are: homogenizing temperature of 70°C to 90°C, homogenizing time of 5min to 15min, homogenizing speed of 5krpm to 10krpm; and / or, The second mixing and homogenizing conditions are: homogenizing temperature of 70°C to 90°C, homogenizing time of 5min to 15min, homogenizing speed of 5krpm to 10krpm; and / or, The third mixing and homogenizing conditions are: a homogenizing temperature of 70° C. to 90° C., a homogenizing time of 5 min to 15 min, and a homogenizing speed of 5 krpm to 10 krpm.

10. The method for preparing the arbidol hydrochloride cream for inhibiting HSV-2 according to claim 8, characterized in that: The micronization treatment is a jet milling operation, wherein the feed pressure of the jet milling operation is 5 bar to 7 bar, the milling pressure is 4 bar to 5 bar, and the feed speed is 2 rpm to 8 rpm.

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