Externally applied medicine for verruca vulgaris and preparation method thereof

Abstract

The invention provides an external medicine for verruca vulgaris and a preparation method thereof, and belongs to the technical field of external medicine preparations for skin diseases. The external medicine is mainly prepared from quick lime, caustic soda, lidocaine and purified water according to a set proportion, is prepared into viscous paste through the steps of stirring, heating, cooling and the like, and has the characteristics of strong alkaline corrosion, local analgesia and continuous release. After the medicament is coated on the surface of a wart body, local cutin degeneration and necrosis can be caused within 2-4 hours, so that the wart body naturally falls off. An alkaline cyclic release mechanism is formed through reaction of alkaline components and CO2 in air, and the drug effect persistence is enhanced; the lidocaine is introduced to effectively relieve causalgia and discomfort caused by corrosion stimulation, and the use comfort is improved. The preparation process is simple and convenient, the raw materials are easy to obtain, and the traditional Chinese medicine composition is suitable for industrial production and household use, has the advantages of quick effect, low pain, stable curative effect, no scar and the like, and is suitable for treating various types of verruca vulgaris.

Description

Technical Field

[0001] The present invention relates to the technical field of topical dermatological preparations, and specifically to an external medicine for verruca vulgaris and its preparation method. Background Art

[0002] Verruca vulgaris is a benign skin neoplasm caused by human papillomavirus (HPV) infection. Clinically, it often presents as small papules with rough surfaces and hard textures, in grayish-yellow, brown or normal skin color, and mostly occurs in easily friction-prone areas such as fingers, the back of the hand, soles of the feet, and knees. This disease has a certain degree of infectivity and recurrence, especially with a relatively high incidence rate in children and adolescents. Although verruca vulgaris is a self-limiting disease in medicine, due to its impact on aesthetics, easy infectivity, and long self-healing cycle, most patients still need to achieve treatment through intervention means.

[0003] Currently, the clinical treatment of verruca vulgaris mainly falls into three categories: physical therapy, chemotherapy, and immunotherapy. Physical therapy includes methods such as liquid nitrogen cryotherapy, high-frequency electrocautery, and CO2 laser ablation, which can remove the surface warts in a short time, but often are accompanied by significant pain, long wound repair time, and scar formation, especially not suitable for children or patients with sensitive pain. In terms of chemotherapy, common drugs such as salicylic acid plaster, fluorouracil solution, and potassium hydroxide corrosive solution, although having certain curative effects, have a long treatment cycle, some drugs are highly corrosive, easily irritate the surrounding healthy skin, and the patient compliance is poor. Immunotherapy includes local interferon injection or systemic oral antiviral drugs, but they are costly, have slow effects, and there are also limitations in the applicable population.

[0004] In addition, some traditional external medicines have also been tried for the treatment of verruca vulgaris, such as traditional Chinese medicine corrosive paste or folk prescription preparations, but generally have problems such as unclear components, unstable drug effects, and inability to evaluate safety, and are difficult to be promoted as a standardized treatment method.

[0005] To sum up, the existing treatment methods for verruca vulgaris generally have the following defects: First, the treatment process is accompanied by obvious discomfort, affecting patient compliance; second, the treatment course is long and the recurrence rate is high, lacking fast and effective treatment means; third, there is a lack of an external treatment plan that can take effect quickly and has good comfort. Therefore, there is an urgent need to develop an external treatment preparation with stable drug effects, rapid action, convenient use, and good analgesic performance to meet the actual clinical needs for non-invasive, safe and efficient treatment of verruca vulgaris.

[0006] The present invention precisely aims at the above problems, provides an external ointment with continuous alkaline corrosion ability, good skin adhesion performance, and local anesthetic effect, and proposes a corresponding safe and controllable preparation method. This solution significantly improves the comfort and safety during use while maintaining the treatment effectiveness, and has good industrialization prospects and clinical promotion value. Summary of the Invention

[0007] The object of the present invention is to provide an external medicine for verruca vulgaris and a preparation method thereof to solve the problems raised in the above-mentioned background technology.

[0008] To achieve the above object, the present invention provides the following technical solution: an external medicine for verruca vulgaris and a preparation method thereof. This method realizes the detection of iron content in a strong oxidizing environment of sodium hypochlorite by optimizing the sample pretreatment process, chromogenic reaction system and spectrophotometric determination technology, and specifically includes the following steps:

[0009] (1) Pretreat the sodium hypochlorite solution sample by sequentially adding a reducing agent, a buffer solution and a masking agent to neutralize the oxidizing property of sodium hypochlorite, adjust the pH of the reaction environment to 4.0 - 6.0, and eliminate the interference of other metal ions except iron ions;

[0010] (2) Add a chromogenic agent to the pretreated sample to make the iron ions in the sample undergo a specific reaction with the chromogenic agent to form a stable colored complex;

[0011] (3) Use a spectrophotometer to measure the absorbance of the sample at a specific wavelength, and quantitatively calculate the iron content in the sodium hypochlorite solution according to the standard curve of iron ion concentration and absorbance established in advance.

[0012] As a preferred technical solution of the present invention, the pretreatment in step (1) includes adding a reducing agent to the sodium hypochlorite solution sample to neutralize the oxidizing property of sodium hypochlorite, prevent it from oxidizing the chromogenic agent or interfering with the chromogenic reaction of iron ions, thereby improving the sensitivity and accuracy of the detection.

[0013] As a preferred technical solution of the present invention, the reducing agent is one or a combination of sodium sulfite, sodium dithionite, ascorbic acid or hydrazine compounds, and the addition amount is 0.03 - 0.05 grams of reducing agent per milliliter of sodium hypochlorite solution. After adding, stir at room temperature for 2 - 5 minutes.

[0014] As a preferred technical solution of the present invention, the pretreatment in step (1) further includes adding a buffer solution to adjust the pH of the sample solution to 4.0 - 6.0, provide a stable acidic environment, promote the complexation reaction of iron ions with the chromogenic agent, and at the same time avoid the decomposition of the chromogenic agent caused by too low pH or the precipitation of iron ions caused by too high pH.

[0015] As a preferred technical solution of the present invention, the buffer solution is acetic acid - sodium acetate buffer solution, citric acid - sodium citrate buffer solution or phosphoric acid - disodium hydrogen phosphate buffer solution, and the addition amount is 0.5 - 1.0 times the volume of the sodium hypochlorite sample. After adding, stir for 1 - 2 minutes, and use a pH meter or pH test paper to verify whether the pH value is within the target range.

[0016] As a preferred technical solution of the present invention, the pretreatment in step (1) further includes adding a masking agent to selectively form stable complexes with metal ions other than iron ions in the sample, eliminating their competitive interference with the color reaction of iron ions. The metal ions include copper ions, nickel ions, and zinc ions.

[0017] As a preferred technical solution of the present invention, the masking agent is one or a combination of ethylenediaminetetraacetic acid, citric acid, tartaric acid, or oxalic acid. The addition amount is 0.01 - 0.02 grams of the masking agent per milliliter of sodium hypochlorite solution. After adding, stir at room temperature for 1 - 3 minutes.

[0018] As a preferred technical solution of the present invention, the color reagent in step (2) is one of 1,10 - phenanthroline, potassium thiocyanate, 2,2'-bipyridine, or salicylic acid. The color reagent is added in the form of an aqueous solution with a concentration of 0.1% - 10% (w / v). The addition amount is 0.2 - 0.3 times the volume of the sodium hypochlorite sample. After adding, let it stand at 25 ± 2°C for 5 - 10 minutes to complete the color reaction.

[0019] As a preferred technical solution of the present invention, the measurement wavelength of the spectrophotometer in step (3) is selected according to the type of color reagent, where:

[0020] When using 1,10 - phenanthroline, the measurement wavelength is 510 ± 5 nm;

[0021] When using potassium thiocyanate, the measurement wavelength is 480 ± 5 nm;

[0022] When using 2,2'-bipyridine, the measurement wavelength is 520 ± 5 nm;

[0023] Before measurement, zero the spectrophotometer with a blank solution under the same pretreatment conditions as the sample, and keep the optical path clean during the measurement process.

[0024] Compared with the prior art, the beneficial effects of the present invention are:

[0025] By mixing quicklime and caustic soda in a specific ratio and utilizing their continuous alkaline generation reaction with the participation of water and air, the present invention constructs an external medical ointment with a continuous strong alkali corrosion effect, which can quickly and stably cause the denaturation and necrosis of the wart tissue, thereby realizing the shedding of the wart and the eradication of the lesion. Compared with the existing liquid nitrogen freezing or laser physical means, the present invention does not rely on professional equipment, does not require cold chain transportation or special operating environment, and is suitable for primary medical care and home use.

[0026] The present invention introduces lidocaine as a local anesthetic component, which can effectively relieve the discomfort caused by alkaline corrosion while ensuring the treatment effect, avoiding side effects such as stinging, burning, and swelling during the use of traditional chemical corrosion drugs, and significantly improving the comfort of use and patient compliance. The formulations with different concentrations and alkalinities can also be flexibly adjusted according to the individual tolerance of patients, so as to achieve personalized treatment.

[0027] The preparation process of the present invention is simple, the raw materials are widely sourced, the finished product has good stability, and it is convenient for industrial mass production and long-term storage. The use method of the medicament is simple and the effect is quick. The treatment effect can be achieved within 2 to 4 hours of a single application. Most patients' warts will naturally fall off within a week without leaving scars, which has significant clinical application value and market promotion potential. Detailed implementation manners

[0028] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0029] The present invention provides an external ointment for treating verruca vulgaris, which uses basic raw materials such as quicklime, caustic soda, lidocaine, and purified water, and through specific ratios and control processes, obtains a paste-like external medicine with film-forming property, sustained-release property, and alkaline corrosion function, which can achieve local necrosis and shedding of the wart tissue. By regulating the proportion of alkaline components, water content, and concentration of anesthetic components, it can be adapted to different lesion thicknesses and different patient tolerance levels, and is particularly suitable for high-incidence areas of verruca vulgaris such as fingers, foot edges, elbows, and knees. The ointment causes keratin denaturation and necrosis through strong alkali, and at the same time, by means of the reaction of CO2 in the air with NaOH to form Na2CO3, and then reacting with Ca(OH)2 to generate new NaOH and precipitate CaCO3, a continuous regeneration reaction of alkaline active components is realized, improving the persistence of drug efficacy. Lidocaine, as a local anesthetic component, can effectively relieve the discomfort of patients during the treatment process and improve the compliance of use.

[0030] The preparation method of the external medicine of the present invention is simple, adopting conventional heating, stirring, and low-temperature mixing processes, without the need for organic solvents or high-pressure equipment, and is suitable for home use, primary medical care, and industrial large-scale production. The following further clarifies the technical content of the present invention through multiple embodiments.

[0031] In Example 1, 15 parts of quicklime and 15 parts of caustic soda were weighed, fully mixed in a dry container, and sealed for 18 hours for pre-activation. The mixture was slowly added to 15 parts of purified water, and gently heated at 70 °C for 15 minutes under stirring conditions to form a thick paste-like liquid. After cooling to 25 °C, a lidocaine aqueous solution (with a total amount of 0.3 parts) was added, and stirring was continued for 8 minutes to obtain a grayish-white homogeneous paste. The obtained preparation was filled into an aluminum foil hose and stored in the dark. When in use, the drug with a thickness of about 1.5 mm was evenly applied on the surface of the wart, and after applying for 3 hours, it was washed off. This scheme is suitable for most patients with medium-thickness warts, has good film-forming properties and stable drug efficacy release. The wart naturally falls off within about 2 to 3 days, the patient has basically no obvious stabbing pain, and the satisfaction rate reaches 96%.

[0032] Example 2 adopted a low-alkali mild formula, taking 12 parts of quicklime, 10 parts of caustic soda, 18 parts of purified water, and 0.3 parts of lidocaine, and was prepared according to the same process as Example 1, controlling the reaction temperature at 65 °C and the heating time at 12 minutes. The obtained paste was softer but non-flowing, with a slightly lower pH value, and was suitable for patients with sensitive skin or first-time treatment. After use, the wart showed an albino dehydration reaction starting from 3.5 hours, the effect was milder, the patient had no stabbing pain reaction, and it was especially suitable for facial or pediatric use scenarios, with a satisfaction rate of 92%.

[0033] Example 3 was a high-alkali concentrated preparation, using 20 parts of quicklime, 18 parts of caustic soda, 10 parts of purified water, and 0.5 parts of lidocaine, controlling the reaction temperature at 80 °C and the stirring and heating time at 15 minutes. The prepared paste was thick and had strong adhesiveness, and the alkalinity was significantly enhanced, which was beneficial for the rapid treatment of thick keratotic warts. During the actual use process, it was observed that the wart became hard and black within 2 hours and automatically fell off within 3 days. Although the analgesic effect was significant, some patients still reported a slight stabbing pain at the local area. It was suitable for patients with hard warts and severe lesion keratinization, and the satisfaction rate was 88%.

[0034] In Comparative Example 1, the same ratio as in Example 1 was used, but lidocaine was not added, and other preparation and use processes were the same. Although the drug efficacy remained unchanged, about 75% of the users reported different degrees of burning and stabbing pain during the treatment process, and 8 subjects terminated the use in advance due to discomfort, and the satisfaction rate dropped significantly to 62%. This comparison clearly shows the role of the anesthetic component in improving user tolerance, thus proving that lidocaine is an indispensable technical element constituting the present invention.

[0035] For the convenience of analyzing the efficacy differences of each example, the experimental data are summarized as follows:

[0036]

[0037]

[0038] The results show that reasonably controlling the ratio of the alkaline component to lidocaine can not only achieve a rapid verruca removal effect, but also take into account drug safety and user experience. Among them, Example 1 shows the most balanced performance and the best comprehensive effect. Example 2 is suitable for low-tolerance populations, and Example 3 is suitable for severe lesions, while the comparative example confirms the important value of the local anesthetic component in reducing adverse sensations.

[0039] The technical solution provided by the present invention is not only superior to existing physical methods such as liquid nitrogen freezing and high-frequency electrocautery in terms of drug efficacy persistence, adaptability, and safety, but also superior to conventional chemical means such as acidic ointments and corrosive ointments, and has significant technical innovation points and industrial transformation prospects.

[0040] The content not described in detail in this specification belongs to the prior art well-known to those skilled in the art. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments, or perform equivalent replacements on some of the technical features. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. An external medicine for verruca vulgaris, characterized in that, Comprising the following components in parts by weight: Quicklime CaO 12 - 20 parts, caustic soda NaOH 10 - 18 parts, lidocaine 0.1 - 0.5 parts, purified water 10 - 20 parts; The medicament is a paste, showing grayish white or light yellow, having strong alkaline corrosive effect, good skin adhesion and local analgesic function, and being used for chemically necrotizing and exfoliating verruca tissues.

2. The topical medicine for verruca vulgaris according to claim 1, characterized in that, The preferred mass ratio of the quicklime, caustic soda, purified water and lidocaine is 15:15:15:0.

3. The obtained paste has a pH value of 12.2 - 12.8, is in a viscous paste state, and can stably adhere to the skin surface for no less than 3 hours after application.

3. The external medicine for verruca vulgaris according to claim 1, characterized in that, The water content in the paste is controlled at 12% - 16%, having excellent film-forming property and sustained-release characteristics, and continuously maintaining the release of the active pharmaceutical ingredient and the local concentration during the drug efficacy period.

4. The external medicine for verruca vulgaris according to claim 1, characterized in that, The lidocaine is lidocaine hydrochloride powder for local epidermis or lidocaine aqueous solution, which is evenly distributed in the paste to form an effective anesthetic concentration of 0.2% - 1.0%, effectively relieving the irritation and burning pain during the alkaline corrosion process.

5. The topical medicine for verruca vulgaris according to claim 1, characterized in that, This medicament is applicable to treating common verruca high-incidence areas such as fingers, the back of hands, the edges of feet, knees, elbows, etc., and also has significant therapeutic effects on keratinized verruca and multiple verruca. The single-use duration is 1.5 - 4 hours. After single use, the verruca tissues of most patients necrotize and exfoliate, and no scar remains in the later healing process.

6. A method for preparing an external medicine for verruca vulgaris according to any one of claims 1-5, characterized in that, Including the following steps: (1) Weigh quicklime and caustic soda, mix them evenly according to the set ratio of 12 - 20 parts:10 - 18 parts, and then seal and stand still for 12 - 24 hours to stabilize the reactivity of the raw materials; (2) Slowly add 10 - 20 parts of purified water dropwise to the mixture under stirring, control the reaction temperature between 60 - 80°C, and heat with gentle fire for 10 - 20 minutes to form a uniform paste; The reactions occurring during this period include: CaO + H2O → Ca(OH)2 (exothermic) 2NaOH + CO2 → Na2CO3 + H2O Na2CO3 + Ca(OH)2 → 2NaOH + CaCO3↓ (3) Cool the obtained paste to room temperature of 20 - 30°C, add 0.1 - 0.5 parts of lidocaine powder or aqueous solution, and continue stirring for 5 - 10 minutes to form a stable paste; (4) Pack it into an aluminum-plastic composite hose or a medical light-shielding plastic can, and store it sealed and away from light.

7. The preparation method of the external medicine for verruca vulgaris according to claim 6, characterized in that, The purified water is added in three portions during the dropping process, with an interval of 2 - 5 minutes each time.

8. The preparation method of the external medicine for verruca vulgaris according to claim 6, characterized in that, After the paste is prepared, its initial pH value is stably maintained between 11.8 - 13.2, having the ability of continuous alkaline release, and relying on the natural absorption of CO2 in the air to complete the cyclic regeneration reaction of NaOH, effectively prolonging the drug activity time.

9. The preparation method of the external medicine for treating verruca vulgaris according to claim 6, wherein, Lidocaine is added in the form of an aqueous solution to enhance its stability and uniform distribution in the alkaline environment, and form an anesthetic sustained-release layer in the preparation, ensuring no burning pain reaction during drug administration.

10. The preparation method of the external medicine for verruca vulgaris according to claim 6, characterized in that, This method is applicable to industrial batch production of 5 kg - 100 kg level. The obtained product can be stably stored for 6 - 12 months at 15 - 30°C and away from light, with unchanged drug efficacy and good physical and chemical properties.

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