CN114159483A - Combined medicine for treating condyloma acuminatum and preparation method and use method thereof - Google Patents
Combined medicine for treating condyloma acuminatum and preparation method and use method thereof Download PDFInfo
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- CN114159483A CN114159483A CN202111552302.6A CN202111552302A CN114159483A CN 114159483 A CN114159483 A CN 114159483A CN 202111552302 A CN202111552302 A CN 202111552302A CN 114159483 A CN114159483 A CN 114159483A
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to the technical field of condyloma acuminatum, in particular to a combined medicament for treating condyloma acuminatum and a preparation method and a using method thereof, the medicament is divided into a wart removing agent and a protective agent which are matched for use, not only can quickly remove warts, but also can reduce the irritation of the medicament, protect normal skin near the warts and promote wound healing, and can kill HPV (human papillomavirus) viruses in deep layers of the skin and reduce the recurrence rate, the wart removing agent is a gel, and is added with compound powerful wart removing components such as podophyllotoxin, imiquimod, cantharidin, brucea javanica extract and the like, and the gel is smeared on the condyloma acuminatum and can quickly induce the apoptosis of warts so as to quickly drop the warts; the protective agent is a spray, effective components such as anti-HPV yolk antibody (IGY), recombinant human alpha-2 b interferon, green tea extract and the like are added, the IGY can specifically kill HPV virus, the recombinant human alpha-2 b interferon and the green tea extract can stimulate the proliferation of immunosuppressive virus, and the combination of various components can thoroughly eliminate the HPV virus of the skin, thereby greatly reducing the recurrence rate.
Description
Technical Field
The invention relates to the technical field of treatment of condyloma acuminatum, and in particular relates to a combined medicine for treating condyloma acuminatum, and a preparation method and a use method thereof.
Background
Condyloma acuminata is a sexually transmitted disease. Most occur in young and middle-aged people of 18-50 years old. Condyloma acuminata is caused by infection with Human Papillomavirus (HPV) and is primarily manifested as proliferative lesions in the anogenital area. Condyloma acuminata can cause small cone-shaped fleshy pimples at the early stage, generally occurs in the external genitalia and around the anus, is mostly pink and vegetable, has a very fragile surface, can be easily removed by hands, and is also easy to bleed and infect. The latent period of condyloma acuminatum varies from one person to another, and generally ranges from 2 weeks to 10 months, with an average of 3 months. The individual length is about 12 months. The incidence of condyloma acuminatum is increased year by year, and the health and the life quality of people are seriously influenced.
The medicines for treating condyloma acuminatum in the market at present are generally poor in curative effect, are easy to relapse after being treated and have serious adverse reactions, for example, CN02153460.8 provides a composite medicine for treating condyloma acuminatum and a preparation method thereof, the composite medicine is composed of radix sophorae flavescentis, salicylic acid, podophyllotoxin and borneol, the composite medicine has low curative effect and cannot effectively kill HPV viruses in the deep layer of skin, and the recurrence is easy to cause, and the salicylic acid, the podophyllotoxin and the borneol in the composite medicine are all components with large skin irritation and are easy to cause serious adverse reactions when contacting normal skin.
Disclosure of Invention
The invention aims to provide a combined medicament for treating condyloma acuminatum, which has good curative effect and no adverse reaction after use, and a preparation method and a use method thereof, aiming at the defects in the prior art.
The purpose of the invention is realized by the following technical scheme:
a combined medicine for treating condyloma acuminatum comprises a wart removing agent and a protective agent which are mutually matched, wherein the wart removing agent is a gel, the protective agent is a spray, and the combined medicine comprises the following components in percentage by weight:
the wart removing agent consists of the following raw materials in percentage by weight:
5 to 10 percent of podophyllotoxin imiquimod cantharidin composite nano liposome
2 to 5 percent of brucea javanica extract
1 to 2 percent of carbomer
1 to 2 percent of triethanolamine
1 to 3 percent of 1, 2 pentanediol
5 to 15 percent of glycerin
70% -90% of purified water;
the podophyllotoxin imiquimod cantharidin composite nano-liposome has the function of inducing apoptosis and leading wart bodies to fall off quickly; the brucea javanica extract has the functions of killing parasites, relieving itching, inhibiting cell division and inducing apoptosis.
The protective agent consists of the following raw materials in percentage by weight:
3% -6% of anti-HPV yolk antibody recombinant human alpha-2 b interferon composite nano-liposome
2 to 10 percent of green tea extract
2 to 5 percent of carboxymethyl chitosan
1 to 3 percent of 1, 2 pentanediol
70-90% of purified water.
The anti-HPV yolk antibody recombinant human alpha-2 b interferon composite nano liposome comprises the following components: has effects of resisting virus, enhancing immunity, inhibiting wart proliferation, completely killing HPV virus in deep layer of skin, and reducing recurrence rate of condyloma acuminatum.
The green tea extract has the effects of stimulating immunity and inhibiting the proliferation of HPV virus.
The carboxymethyl chitosan is used as a film forming agent, so that a layer of protective film can be quickly formed by spraying a medicine on the skin, the carboxymethyl chitosan has excellent bacteriostatic property and can protect a wound and promote the wound healing, and meanwhile, the effective components can be stored in the carboxymethyl chitosan protective film to play a slow release role so as to prolong the action time of the medicine. The protective agent can be sprayed to form a film to protect normal skin around wart body, and reduce the influence of irritative components such as podophyllotoxin and imiquimod on peripheral skin; the strong components in the protective agent slowly enter the deep layer of the skin, thoroughly kill HPV virus and reduce the recurrence rate.
The preparation method of the combined medicine for treating condyloma acuminatum comprises the preparation method of a wart removing agent and the preparation method of a protective agent:
the preparation method of the wart removing agent comprises the following steps:
firstly, adding purified water, glycerol and brucea javanica extract in a formula ratio into a reaction kettle, and stirring to uniformly mix the materials;
secondly, stopping stirring, uniformly scattering carbomer in a formula amount on the liquid level of the reaction kettle, and standing for swelling for more than 12H;
thirdly, after full swelling, stirring to make the materials uniform;
fourthly, adding triethanolamine with the formula amount from a feeding port under the condition of stirring, and continuing stirring for 1H after the addition is finished;
fifthly, adding podophyllotoxin imiquimod cantharidin composite nano liposome and 1, 2 pentanediol according to the formula amount, and stirring to fully and uniformly mix the materials to obtain a wart removing agent;
the preparation process of the protective agent comprises the following steps:
firstly, weighing purified water and a green tea extract according to the formula amount, adding the purified water and the green tea extract into a reaction kettle, and stirring to fully dissolve the materials;
secondly, weighing carboxymethyl chitosan with the formula amount, adding the carboxymethyl chitosan into a reaction kettle, and stirring to fully dissolve the materials;
and secondly, weighing the anti-HPV yolk antibody recombinant human alpha-2 b interferon composite nano liposome and 1, 2 pentanediol in the formula amount, adding into the reaction kettle, and continuously stirring to fully and uniformly mix the materials to obtain the protective agent.
Further, the podophyllotoxin imiquimod cantharidin composite nano liposome comprises the following preparation steps:
firstly, weighing 30-50 parts by weight of nonionic surfactant Brij78, adding 3000-5000 parts by weight of ultrapure water, and performing ultrasonic dissolution to obtain a water phase;
secondly, weighing 8-12 parts by weight of soybean lecithin, adding 1500-2500 parts by weight of absolute ethyl alcohol, and performing ultrasonic dissolution to obtain an ethanol solution;
thirdly, weighing 3-5 parts by weight of podophyllotoxin, 1-3 parts by weight of imiquimod, 1-2 parts by weight of cantharidin, 8-12 parts by weight of glyceryl monostearate and 30-40 parts by weight of tricaprylin, adding 1500-2500 parts by weight of dichloromethane, and performing ultrasonic treatment to completely dissolve the dichloromethane to obtain a dichloromethane solution;
step four, uniformly mixing the ethanol solution obtained in the step two and the dichloromethane solution obtained in the step three to obtain an oil phase;
fifthly, heating the oil phase to 70-75 ℃, slowly injecting the oil phase into a 75 ℃ constant-temperature water phase in stirring at 1000-;
and sixthly, quickly and uniformly mixing the concentrated emulsion obtained in the fifth step with 0 ℃ ice water in an ice bath, wherein the weight ratio of the concentrated emulsion to the 0 ℃ ice water is 1: and 1, ultrasonically stirring in an ice-water bath for 30min to obtain the podophyllotoxin imiquimod cantharidin composite nano liposome.
Further, the anti-HPV yolk antibody recombinant human alpha-2 b interferon composite nano-liposome comprises the following preparation steps:
step one, preparing a PBS buffer solution with the pH value of 5-7;
secondly, dissolving 10-20 parts by weight of anti-HPV yolk antibody and 10-20 parts by weight of recombinant human alpha-2 b interferon in 400-500 parts by weight of PBS buffer solution to be used as a water phase for later use;
thirdly, weighing 400 parts by weight of 300-400 parts by weight of diethyl ether and 600 parts by weight of trichloromethane, and uniformly stirring to obtain a mixed solution;
step four, weighing 250-280 parts by weight of yolk lecithin and 20-50 parts by weight of cholesterol, adding the yolk lecithin and the cholesterol into the mixed solution obtained in the step three, and slowly stirring the mixture to dissolve the yolk lecithin and the cholesterol to obtain an organic phase for later use;
step five, slowly injecting the water phase in the step two into the organic phase in the step four, and ultrasonically stirring by using an ultrasonic stirrer to obtain mixed liquid;
sixthly, carrying out vacuum rotary evaporation on the mixed liquid obtained in the fifth step at the temperature of 35-45 ℃ to remove ether and trichloromethane;
and seventhly, adding 3000-4000 parts by weight of PBS buffer solution and 100-200 parts by weight of Tween-60 into the material after rotary evaporation, and continuing ultrasonic stirring to completely dissolve the material to obtain the anti-HPV yolk antibody recombinant human alpha-2 b interferon composite nano-liposome.
The use method of the combined medicine for treating condyloma acuminatum adopts the following 2 steps:
the method comprises the following steps: spraying protective agent on the affected part with condyloma acuminatum and the peripheral skin;
step two: after the protective agent is dried to form a film, the film on the wart body is rubbed with a cotton bud and then coated with the wart removing agent.
The wart removing agent is used for 2-3 times per day for three days, and then is stopped for four days, and the protective agent is used for 2-3 times per day for seven days as a treatment course.
The wart removing agent is stopped immediately after the wart falls off, and the protective agent is continuously used.
The invention has the beneficial effects that:
1. the medicine is divided into two parts of a wart removing agent and a protective agent which are matched for use, so that warts can be removed quickly, irritation of the medicine can be reduced, normal skin near the warts can be protected, wound healing can be promoted, HPV viruses in the deep layer of the skin can be killed, and the recurrence rate can be reduced.
2. The wart removing agent is a gel, compound powerful wart removing components such as podophyllotoxin, imiquimod, cantharidin, brucea javanica extract and the like are added, and the gel is smeared on condyloma acuminatum warts and can rapidly induce apoptosis of wart cells so as to enable the wart bodies to fall off rapidly; the protective agent is a spraying agent, effective components such as an anti-HPV yolk antibody (IGY), recombinant human alpha-2 b interferon, a green tea extract and the like are added, the anti-HPV yolk protein (IGY) can specifically kill HPV viruses, the recombinant human alpha-2 b interferon and the green tea extract can stimulate the proliferation of immunosuppressive viruses, and the combination of various components can thoroughly eliminate the HPV viruses on the skin, so that the recurrence rate is greatly reduced. The protective agent is also added with a film forming component carboxymethyl chitosan, so that the medicine can form a layer of protective film when sprayed to a patient, simultaneously, the carboxymethyl chitosan has good bacteriostatic property and can prevent wounds from being inflamed, and in addition, the effective components can be stored in the protective film and can also play a role in slowly releasing the effective components, thereby prolonging the action time of the medicine.
3. In the preparation method, the anti-HPV yolk antibody (IGY) and the recombinant human alpha-2 b interferon are prepared into the composite nano liposome, and the podophyllotoxin, the imiquimod and the cantharidin are prepared into the composite nano liposome, so that the stability of the IGY and the recombinant human alpha-2 b interferon in a preparation is greatly enhanced, the podophyllotoxin, the imiquimod and the cantharidin can be fully dispersed and dissolved in a gel preparation, the transdermal absorption of effective components is greatly enhanced, the curative effect of the medicine is enhanced, and the action time of the medicine is prolonged.
Detailed Description
The invention is further described with reference to the following examples.
Example 1
A combined medicine for treating condyloma acuminatum comprises a wart removing agent and a protective agent which are mutually matched, wherein the wart removing agent is a gel, the protective agent is a spray, and the combined medicine comprises the following components in percentage by weight:
the wart removing agent consists of the following raw materials in percentage by weight:
podophyllotoxin imiquimod cantharidin composite nano liposome 5%
Brucea javanica extract 5%
2 percent of carbomer
Triethanolamine 2%
1, 2-pentanediol 3%
10 percent of glycerin
73% of purified water;
the protective agent consists of the following raw materials in percentage by weight:
anti-HPV yolk antibody recombinant human alpha-2 b interferon composite nano liposome 3%
Green tea extract 2%
2 percent of carboxymethyl chitosan
1, 2-pentanediol 3%
Purified water 90%.
The preparation method of the combined medicine for treating condyloma acuminatum comprises the preparation method of a wart removing agent and the preparation method of a protective agent:
the preparation method of the wart removing agent comprises the following steps:
firstly, adding purified water, glycerol and brucea javanica extract in a formula ratio into a reaction kettle, and stirring to uniformly mix the materials;
secondly, stopping stirring, uniformly scattering carbomer in a formula amount on the liquid level of the reaction kettle, and standing for swelling for more than 12H;
thirdly, after full swelling, stirring to make the materials uniform;
fourthly, adding triethanolamine with the formula amount from a feeding port under the condition of stirring, and continuing stirring for 1H after the addition is finished;
fifthly, adding podophyllotoxin imiquimod cantharidin composite nano liposome and 1, 2 pentanediol according to the formula amount, and stirring to fully and uniformly mix the materials to obtain a wart removing agent;
the preparation process of the protective agent comprises the following steps:
firstly, weighing purified water and a green tea extract according to the formula amount, adding the purified water and the green tea extract into a reaction kettle, and stirring to fully dissolve the materials;
secondly, weighing carboxymethyl chitosan with the formula amount, adding the carboxymethyl chitosan into a reaction kettle, and stirring to fully dissolve the materials;
and secondly, weighing the anti-HPV yolk antibody recombinant human alpha-2 b interferon composite nano liposome and 1, 2 pentanediol in the formula amount, adding into the reaction kettle, and continuously stirring to fully and uniformly mix the materials to obtain the protective agent.
Further, the podophyllotoxin imiquimod cantharidin composite nano liposome comprises the following preparation steps:
firstly, weighing 30 parts by weight of nonionic surfactant Brij78, adding 3000 parts by weight of ultrapure water, and performing ultrasonic dissolution to obtain a water phase;
secondly, weighing 9 parts by weight of soybean lecithin, adding 1500 parts by weight of absolute ethyl alcohol, and performing ultrasonic dissolution to obtain an ethanol solution;
weighing 4 parts by weight of podophyllotoxin, 1 part by weight of imiquimod, 2 parts by weight of cantharidin, 10 parts by weight of glyceryl monostearate and 30 parts by weight of tricaprylin, adding 1600 parts by weight of dichloromethane, and performing ultrasonic treatment to completely dissolve the dichloromethane to obtain a dichloromethane solution;
step four, uniformly mixing the ethanol solution obtained in the step two and the dichloromethane solution obtained in the step three to obtain an oil phase;
fifthly, heating the oil phase to 70-75 ℃, slowly injecting the oil phase into a 75 ℃ constant-temperature water phase in stirring at 1000-;
and sixthly, quickly and uniformly mixing the concentrated emulsion obtained in the fifth step with 0 ℃ ice water in an ice bath, wherein the weight ratio of the concentrated emulsion to the 0 ℃ ice water is 1: and 1, ultrasonically stirring in an ice-water bath for 30min to obtain the podophyllotoxin imiquimod cantharidin composite nano liposome.
Further, the anti-HPV yolk antibody recombinant human alpha-2 b interferon composite nano-liposome comprises the following preparation steps:
step one, preparing a PBS buffer solution with the pH value of 5;
secondly, dissolving 18 parts by weight of anti-HPV yolk antibody and 20 parts by weight of recombinant human alpha-2 b interferon in 450 parts by weight of PBS buffer solution to be used as a water phase for later use;
step three, weighing 300 parts by weight of diethyl ether and 600 parts by weight of trichloromethane, and uniformly stirring to obtain a mixed solution;
step four, weighing 250 parts by weight of egg yolk lecithin and 50 parts by weight of cholesterol, adding the egg yolk lecithin and the cholesterol into the mixed solution obtained in the step three, and slowly stirring the mixture to dissolve the egg yolk lecithin and the cholesterol to obtain an organic phase for later use;
step five, slowly injecting the water phase in the step two into the organic phase in the step four, and ultrasonically stirring by using an ultrasonic stirrer to obtain mixed liquid;
sixthly, carrying out vacuum rotary evaporation on the mixed liquid obtained in the fifth step at the temperature of 35-45 ℃ to remove ether and trichloromethane;
seventhly, adding 3600 parts by weight of PBS buffer solution and 150 parts by weight of Tween-60 into the rotary evaporated material, and continuing ultrasonic stirring to completely dissolve the material to obtain the anti-HPV yolk antibody recombinant human alpha-2 b interferon composite nano-liposome.
The use method of the combined medicine for treating condyloma acuminatum adopts the following 2 steps:
the method comprises the following steps: spraying protective agent on the affected part with condyloma acuminatum and the peripheral skin;
step two: after the protective agent is dried to form a film, the film on the wart body is rubbed with a cotton bud and then coated with the wart removing agent.
The wart removing agent is used for 2-3 times per day for three days, and then is stopped for four days, and the protective agent is used for 2-3 times per day for seven days as a treatment course.
The wart removing agent is stopped immediately after the wart falls off, and the protective agent is continuously used.
Example 2
A combined medicine for treating condyloma acuminatum comprises a wart removing agent and a protective agent which are mutually matched, wherein the wart removing agent is a gel, the protective agent is a spray, and the combined medicine comprises the following components in percentage by weight:
the wart removing agent consists of the following raw materials in percentage by weight:
podophyllotoxin imiquimod cantharidin composite nano liposome 6%
Brucea javanica extract 4%
2 percent of carbomer
1 percent of triethanolamine
1, 2-pentanediol 2%
Glycerol 5%
80% of purified water;
the protective agent consists of the following raw materials in percentage by weight:
anti-HPV yolk antibody recombinant human alpha-2 b interferon composite nano-liposome 4%
Green tea extract 6%
3 percent of carboxymethyl chitosan
1, 2-pentanediol 2%
85% of purified water.
The preparation method of the combined medicine for treating condyloma acuminatum comprises the preparation method of a wart removing agent and the preparation method of a protective agent:
the preparation method of the wart removing agent comprises the following steps:
firstly, adding purified water, glycerol and brucea javanica extract in a formula ratio into a reaction kettle, and stirring to uniformly mix the materials;
secondly, stopping stirring, uniformly scattering carbomer in a formula amount on the liquid level of the reaction kettle, and standing for swelling for more than 12H;
thirdly, after full swelling, stirring to make the materials uniform;
fourthly, adding triethanolamine with the formula amount from a feeding port under the condition of stirring, and continuing stirring for 1H after the addition is finished;
fifthly, adding podophyllotoxin imiquimod cantharidin composite nano liposome and 1, 2 pentanediol according to the formula amount, and stirring to fully and uniformly mix the materials to obtain a wart removing agent;
the preparation process of the protective agent comprises the following steps:
firstly, weighing purified water and a green tea extract according to the formula amount, adding the purified water and the green tea extract into a reaction kettle, and stirring to fully dissolve the materials;
secondly, weighing carboxymethyl chitosan with the formula amount, adding the carboxymethyl chitosan into a reaction kettle, and stirring to fully dissolve the materials;
and secondly, weighing the anti-HPV yolk antibody recombinant human alpha-2 b interferon composite nano liposome and 1, 2 pentanediol in the formula amount, adding into the reaction kettle, and continuously stirring to fully and uniformly mix the materials to obtain the protective agent.
Further, the podophyllotoxin imiquimod cantharidin composite nano liposome comprises the following preparation steps:
firstly, weighing 50 parts by weight of nonionic surfactant Brij78, adding 4000 parts by weight of ultrapure water, and performing ultrasonic dissolution to obtain a water phase;
secondly, weighing 10 parts by weight of soybean lecithin, adding 2000 parts by weight of absolute ethyl alcohol, and performing ultrasonic dissolution to obtain an ethanol solution;
weighing 5 parts by weight of podophyllotoxin, 2 parts by weight of imiquimod, 2 parts by weight of cantharidin, 10 parts by weight of glyceryl monostearate and 35 parts by weight of tricaprylin, adding 2000 parts by weight of dichloromethane, and performing ultrasonic treatment to completely dissolve the dichloromethane to obtain a dichloromethane solution;
step four, uniformly mixing the ethanol solution obtained in the step two and the dichloromethane solution obtained in the step three to obtain an oil phase;
fifthly, heating the oil phase to 70-75 ℃, slowly injecting the oil phase into a 75 ℃ constant-temperature water phase in stirring at 1000-;
and sixthly, quickly and uniformly mixing the concentrated emulsion obtained in the fifth step with 0 ℃ ice water in an ice bath, wherein the weight ratio of the concentrated emulsion to the 0 ℃ ice water is 1: and 1, ultrasonically stirring in an ice-water bath for 30min to obtain the podophyllotoxin imiquimod cantharidin composite nano liposome.
Further, the anti-HPV yolk antibody recombinant human alpha-2 b interferon composite nano-liposome comprises the following preparation steps:
step one, preparing a PBS buffer solution with the pH value of 6;
secondly, dissolving 12 parts by weight of anti-HPV yolk antibody and 12 parts by weight of recombinant human alpha-2 b interferon in 460 parts by weight of PBS buffer solution to be used as a water phase for later use;
step three, weighing 400 parts by weight of diethyl ether and 400 parts by weight of trichloromethane, and uniformly stirring to obtain a mixed solution;
step four, weighing 270 parts by weight of egg yolk lecithin and 30 parts by weight of cholesterol, adding the egg yolk lecithin and the cholesterol into the mixed solution obtained in the step three, and slowly stirring the mixture to dissolve the egg yolk lecithin and the cholesterol to obtain an organic phase for later use;
step five, slowly injecting the water phase in the step two into the organic phase in the step four, and ultrasonically stirring by using an ultrasonic stirrer to obtain mixed liquid;
sixthly, carrying out vacuum rotary evaporation on the mixed liquid obtained in the fifth step at the temperature of 35-45 ℃ to remove ether and trichloromethane;
and seventhly, adding 4000 parts by weight of PBS buffer solution and 180 parts by weight of Tween-60 into the rotary evaporated material, and continuing to ultrasonically stir to completely dissolve the material to obtain the anti-HPV yolk antibody recombinant human alpha-2 b interferon composite nano-liposome.
The use method of the combined medicine for treating condyloma acuminatum adopts the following 2 steps:
the method comprises the following steps: spraying protective agent on the affected part with condyloma acuminatum and the peripheral skin;
step two: after the protective agent is dried to form a film, the film on the wart body is rubbed with a cotton bud and then coated with the wart removing agent.
The wart removing agent is used for 2-3 times per day for three days, and then is stopped for four days, and the protective agent is used for 2-3 times per day for seven days as a treatment course.
The wart removing agent is stopped immediately after the wart falls off, and the protective agent is continuously used.
Example 3
A combined medicine for treating condyloma acuminatum comprises a wart removing agent and a protective agent which are mutually matched, wherein the wart removing agent is a gel, the protective agent is a spray, and the combined medicine comprises the following components in percentage by weight:
the wart removing agent consists of the following raw materials in percentage by weight:
podophyllotoxin imiquimod cantharidin composite nano liposome 10%
Brucea javanica extract 3%
Carbomer 1%
1 percent of triethanolamine
1, 2-pentanediol 1%
5 percent of glycerin
79% of purified water;
the protective agent consists of the following raw materials in percentage by weight:
anti-HPV yolk antibody recombinant human alpha-2 b interferon composite nano-liposome 6%
Green tea extract 10%
4 percent of carboxymethyl chitosan
1, 2-pentanediol 2%
78% of purified water.
The preparation method of the combined medicine for treating condyloma acuminatum comprises the preparation method of a wart removing agent and the preparation method of a protective agent:
the preparation method of the wart removing agent comprises the following steps:
firstly, adding purified water, glycerol and brucea javanica extract in a formula ratio into a reaction kettle, and stirring to uniformly mix the materials;
secondly, stopping stirring, uniformly scattering carbomer in a formula amount on the liquid level of the reaction kettle, and standing for swelling for more than 12H;
thirdly, after full swelling, stirring to make the materials uniform;
fourthly, adding triethanolamine with the formula amount from a feeding port under the condition of stirring, and continuing stirring for 1H after the addition is finished;
fifthly, adding podophyllotoxin imiquimod cantharidin composite nano liposome and 1, 2 pentanediol according to the formula amount, and stirring to fully and uniformly mix the materials to obtain a wart removing agent;
the preparation process of the protective agent comprises the following steps:
firstly, weighing purified water and a green tea extract according to the formula amount, adding the purified water and the green tea extract into a reaction kettle, and stirring to fully dissolve the materials;
secondly, weighing carboxymethyl chitosan with the formula amount, adding the carboxymethyl chitosan into a reaction kettle, and stirring to fully dissolve the materials;
and secondly, weighing the anti-HPV yolk antibody recombinant human alpha-2 b interferon composite nano liposome and 1, 2 pentanediol in the formula amount, adding into the reaction kettle, and continuously stirring to fully and uniformly mix the materials to obtain the protective agent.
Further, the podophyllotoxin imiquimod cantharidin composite nano liposome comprises the following preparation steps:
firstly, weighing 45 parts by weight of nonionic surfactant Brij78, adding 3500 parts by weight of ultrapure water, and carrying out ultrasonic dissolution to obtain a water phase;
secondly, weighing 8 parts by weight of soybean lecithin, adding 1500 parts by weight of absolute ethyl alcohol, and performing ultrasonic dissolution to obtain an ethanol solution;
weighing 4 parts by weight of podophyllotoxin, 3 parts by weight of imiquimod, 2 parts by weight of cantharidin, 12 parts by weight of glyceryl monostearate and 40 parts by weight of tricaprylin, adding 2200 parts by weight of dichloromethane, and performing ultrasonic treatment to completely dissolve the dichloromethane to obtain a dichloromethane solution;
step four, uniformly mixing the ethanol solution obtained in the step two and the dichloromethane solution obtained in the step three to obtain an oil phase;
fifthly, heating the oil phase to 70-75 ℃, slowly injecting the oil phase into a 75 ℃ constant-temperature water phase in stirring at 1000-;
and sixthly, quickly and uniformly mixing the concentrated emulsion obtained in the fifth step with 0 ℃ ice water in an ice bath, wherein the weight ratio of the concentrated emulsion to the 0 ℃ ice water is 1: and 1, ultrasonically stirring in an ice-water bath for 30min to obtain the podophyllotoxin imiquimod cantharidin composite nano liposome.
Further, the anti-HPV yolk antibody recombinant human alpha-2 b interferon composite nano-liposome comprises the following preparation steps:
step one, preparing a PBS buffer solution with the pH value of 7;
secondly, dissolving 18 parts by weight of anti-HPV yolk antibody and 16 parts by weight of recombinant human alpha-2 b interferon in 480 parts by weight of PBS buffer solution to be used as a water phase for later use;
step three, weighing 330 parts by weight of diethyl ether and 440 parts by weight of trichloromethane, and uniformly stirring to obtain a mixed solution;
step four, weighing 250 parts by weight of egg yolk lecithin and 20 parts by weight of cholesterol, adding the egg yolk lecithin and the cholesterol into the mixed solution obtained in the step three, and slowly stirring the mixture to dissolve the egg yolk lecithin and the cholesterol to obtain an organic phase for later use;
step five, slowly injecting the water phase in the step two into the organic phase in the step four, and ultrasonically stirring by using an ultrasonic stirrer to obtain mixed liquid;
sixthly, carrying out vacuum rotary evaporation on the mixed liquid obtained in the fifth step at the temperature of 35-45 ℃ to remove ether and trichloromethane;
seventhly, adding 3200 parts by weight of PBS buffer solution and 120 parts by weight of Tween-60 into the material after rotary evaporation, and continuing to ultrasonically stir the material to completely dissolve the material to obtain the anti-HPV yolk antibody recombinant human alpha-2 b interferon composite nano liposome, namely the use method of the combined medicine for treating condyloma acuminatum, which adopts the following 2 steps:
the method comprises the following steps: spraying protective agent on the affected part with condyloma acuminatum and the peripheral skin;
step two: after the protective agent is dried to form a film, the film on the wart body is rubbed with a cotton bud and then coated with the wart removing agent.
The wart removing agent is used for 2-3 times per day for three days, and then is stopped for four days, and the protective agent is used for 2-3 times per day for seven days as a treatment course.
The wart removing agent is stopped immediately after the wart falls off, and the protective agent is continuously used.
Test group, the medicine prepared in the embodiment 2 of the invention is firstly sprayed on the affected part with condyloma acuminatum and the peripheral skin, after the protective agent is dried to form a film, the film on the wart body is rubbed by a cotton swab, and then the wart removing agent is coated. The wart removing agent is used for 2-3 times per day for three days, and then is stopped for four days, the protective agent is used for 2-3 times per day for seven days as a course of treatment, and the wart removing agent is stopped immediately after the wart body falls off, and the protective agent is continuously used.
In the control group, podophyllotoxin tincture is used for 2 times a day for 3 consecutive days, and the treatment course is 4 days after stopping the drug administration.
3.1 comparison of therapeutic Effect
The medicine is taken for 7 days
| Cure (example) | Effective (example) | Invalid (example) | Cure rate (%) | Total effective rate (%) | Inefficiency (%) | |
| Test group | 5 | 20 | 5 | 16.67 | 83.33 | 16.67 |
| Control group | 2 | 13 | 15 | 6.67 | 50 | 50 |
The medicine is taken for 14 days
| Cure (example) | Effective (example) | Invalid (example) | Cure rate (%) | Total effective rate (%) | Inefficiency (%) | |
| Test group | 20 | 8 | 2 | 66.67 | 93.33 | 6.67 |
| Control group | 5 | 11 | 14 | 16.67 | 53.33 | 46.67 |
The medicine is taken for 21 days
| Cure (example) | Effective (example) | Invalid (example) | Cure rate (%) | Total effective rate (%) | Inefficiency (%) | |
| Test group | 26 | 2 | 2 | 86.67 | 93.33 | 6.67 |
| Control group | 12 | 6 | 12 | 40 | 60 | 40 |
3.2 comparison of relapse rates
| 1 month recurrence Rate (%) | 3 month recurrence Rate (%) | 6-month recurrence Rate (%) | 9-month recurrence Rate (%) | 1 year recurrence Rate (%) | |
| Test group | 0 | 0 | 3.33 | 6.67 | 6.67 |
| Control group | 13.33 | 23.33 | 46.67 | 53.33 | 60 |
3.3 sensitization comparison
In the test group, 30 patients were continuously administered the combination of the present invention for 3 treatment courses, and all the patients showed no allergic reactions except for 2 patients who showed mild erythema at the site of administration.
In the control group, three of 30 patients showed red and swollen allergic reactions in the administered part after two days of administration of podophyllotoxin tincture; 8 cases of the medicine have allergic reaction of red swelling and pruritus after being taken for 1 course of treatment, and 2 cases of the medicine have adverse reaction of skin erosion after being taken for 8 days; after two courses of administration, the total number of patients with adverse reactions increased to 18, wherein 7 patients with serious adverse reactions of erosive edema; after three consecutive courses of podophyllotoxin tincture, only 9 patients with no allergic reaction appeared.
Finally, it should be noted that the above embodiments are only used for illustrating the technical solutions of the present invention, and not for limiting the protection scope of the present invention, although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions can be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.
Claims (7)
1. A combined medicine for treating condyloma acuminatum is characterized in that: the combined medicine comprises two parts of a wart removing agent and a protective agent which are mutually matched, wherein the wart removing agent is a gel, the protective agent is a spray, and the combined medicine specifically comprises the following components:
the wart removing agent consists of the following raw materials in percentage by weight:
5 to 10 percent of podophyllotoxin imiquimod cantharidin composite nano liposome
2 to 5 percent of brucea javanica extract
1 to 2 percent of carbomer
1 to 2 percent of triethanolamine
1 to 3 percent of 1, 2 pentanediol
5 to 15 percent of glycerin
70% -90% of purified water;
the protective agent consists of the following raw materials in percentage by weight:
3% -6% of anti-HPV yolk antibody recombinant human alpha-2 b interferon composite nano-liposome
2 to 10 percent of green tea extract
2 to 5 percent of carboxymethyl chitosan
1 to 3 percent of 1, 2 pentanediol
70-90% of purified water.
2. The method of preparing a combination for the treatment of condyloma acuminatum according to claim 1, wherein: the preparation method comprises a preparation method of a wart removing agent and a preparation method of a protective agent, wherein the preparation method comprises the following steps:
the preparation method of the wart removing agent comprises the following steps:
firstly, adding purified water, glycerol and brucea javanica extract in a formula ratio into a reaction kettle, and stirring to uniformly mix the materials;
secondly, stopping stirring, uniformly scattering carbomer in a formula amount on the liquid level of the reaction kettle, and standing for swelling for more than 12H;
thirdly, after full swelling, stirring to make the materials uniform;
fourthly, adding triethanolamine with the formula amount from a feeding port under the condition of stirring, and continuing stirring for 1H after the addition is finished;
fifthly, adding podophyllotoxin imiquimod cantharidin composite nano liposome and 1, 2 pentanediol according to the formula amount, and stirring to fully and uniformly mix the materials to obtain a wart removing agent;
the preparation process of the protective agent comprises the following steps:
firstly, weighing purified water and a green tea extract according to the formula amount, adding the purified water and the green tea extract into a reaction kettle, and stirring to fully dissolve the materials;
secondly, weighing carboxymethyl chitosan with the formula amount, adding the carboxymethyl chitosan into a reaction kettle, and stirring to fully dissolve the materials;
and secondly, weighing the anti-HPV yolk antibody recombinant human alpha-2 b interferon composite nano liposome and 1, 2 pentanediol in the formula amount, adding into the reaction kettle, and continuously stirring to fully and uniformly mix the materials to obtain the protective agent.
3. The combination as claimed in claim 1, wherein the combination is for treating condyloma acuminatum: the podophyllotoxin imiquimod cantharidin composite nano liposome comprises the following preparation steps:
firstly, weighing 30-50 parts by weight of nonionic surfactant Brij78, adding 3000-5000 parts by weight of ultrapure water, and performing ultrasonic dissolution to obtain a water phase;
secondly, weighing 8-12 parts by weight of soybean lecithin, adding 1500-2500 parts by weight of absolute ethyl alcohol, and performing ultrasonic dissolution to obtain an ethanol solution;
thirdly, weighing 3-5 parts by weight of podophyllotoxin, 1-3 parts by weight of imiquimod, 1-2 parts by weight of cantharidin, 8-12 parts by weight of glyceryl monostearate and 30-40 parts by weight of tricaprylin, adding 1500-2500 parts by weight of dichloromethane, and performing ultrasonic treatment to completely dissolve the dichloromethane to obtain a dichloromethane solution;
step four, uniformly mixing the ethanol solution obtained in the step two and the dichloromethane solution obtained in the step three to obtain an oil phase;
fifthly, heating the oil phase to 70-75 ℃, injecting the oil phase into a 75 ℃ constant-temperature water phase in stirring at 1200r/min with 1000-;
and sixthly, quickly and uniformly mixing the concentrated emulsion obtained in the fifth step with 0 ℃ ice water in an ice bath, wherein the weight ratio of the concentrated emulsion to the 0 ℃ ice water is 1: 1, ultrasonically stirring in an ice-water bath to obtain the podophyllotoxin imiquimod cantharidin composite nano liposome.
4. The combination as claimed in claim 1, wherein the combination is for treating condyloma acuminatum: the anti-HPV yolk antibody recombinant human alpha-2 b interferon composite nano liposome comprises the following preparation steps:
step one, preparing a PBS buffer solution with the pH value of 5-7;
secondly, dissolving 10-20 parts by weight of anti-HPV yolk antibody and 10-20 parts by weight of recombinant human alpha-2 b interferon in 400-500 parts by weight of PBS buffer solution to be used as a water phase for later use;
thirdly, weighing 400 parts by weight of 300-400 parts by weight of diethyl ether and 600 parts by weight of trichloromethane, and uniformly stirring to obtain a mixed solution;
step four, weighing 250-280 parts by weight of yolk lecithin and 20-50 parts by weight of cholesterol, adding the yolk lecithin and the cholesterol into the mixed solution obtained in the step three, and stirring the mixture to dissolve the yolk lecithin and the cholesterol to obtain an organic phase for later use;
step five, slowly injecting the water phase in the step two into the organic phase in the step four, and ultrasonically stirring by using an ultrasonic stirrer to obtain mixed liquid;
sixthly, carrying out vacuum rotary evaporation on the mixed liquid obtained in the fifth step at the temperature of 35-45 ℃ to remove ether and trichloromethane;
and seventhly, adding 3000-4000 parts by weight of PBS buffer solution and 100-200 parts by weight of Tween-60 into the material after rotary evaporation, and continuing ultrasonic stirring to completely dissolve the material, thereby obtaining the anti-HPV yolk antibody recombinant human alpha-2 b interferon composite nano-liposome.
5. The method of using a combination for the treatment of condyloma acuminatum according to any one of claims 1 to 4, wherein: the method comprises the following 2 steps:
the method comprises the following steps: spraying protective agent on the affected part with condyloma acuminatum and the peripheral skin;
step two: after the protective agent is dried to form a film, the film on the wart body is rubbed with a cotton bud and then coated with the wart removing agent.
6. The use of a combination for the treatment of condyloma acuminatum as claimed in claim 5, wherein: the wart removing agent is used for 2-3 times per day for three days, and then is stopped for four days, and the protective agent is used for 2-3 times per day for seven days as a treatment course.
7. The use of a combination for the treatment of condyloma acuminatum as claimed in claim 5, wherein: the wart removing agent is stopped immediately after the wart falls off, and the protective agent is continuously used.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109666685A (en) * | 2018-03-07 | 2019-04-23 | 江苏润洁生物科技有限公司 | The application of HPV Yolk antibody and its drug in preparation treatment HPV infection |
| CN112472763A (en) * | 2020-12-30 | 2021-03-12 | 广西达庆生物科技有限公司 | Compound traditional Chinese medicine gel containing podophyllotoxin and preparation method thereof |
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- 2021-12-17 CN CN202111552302.6A patent/CN114159483A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109666685A (en) * | 2018-03-07 | 2019-04-23 | 江苏润洁生物科技有限公司 | The application of HPV Yolk antibody and its drug in preparation treatment HPV infection |
| CN112472763A (en) * | 2020-12-30 | 2021-03-12 | 广西达庆生物科技有限公司 | Compound traditional Chinese medicine gel containing podophyllotoxin and preparation method thereof |
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| Title |
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| 江中洪等: "鬼臼毒素-固体脂质纳米粒凝胶的制备及质量控制", 《中国药房》 * |
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