An external use time-delayed towel with natural ingredients and a preparation method thereof

Abstract

This invention belongs to the field of traditional Chinese medicine, specifically relating to a delay towel containing dried toad extract and toad oil, and its preparation method. Based on the local anesthetic properties of dried toad extract and toad oil, this invention prepares a topical delay cream by quantitatively controlling the dosage of both, for the treatment of premature ejaculation and erectile dysfunction in men. The delay towel prepared by this invention has the advantages of direct action, individual packaging, immediate use, low cost, and minimal volatility of the active ingredients. This invention not only turns toad oil into a valuable resource and fully explores its medicinal value, but also further improves the rational utilization system of toad resources, providing a practical solution for the efficient development of toad medicinal resources.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine, specifically relating to the preparation of a traditional Chinese medicine external delay towel. Background Technology

[0002] Toads are a general term for the Chinese giant toad (Bufo bufogargarizans Cantor) or the black-rimmed toad (Bufo melanostictus Schneider) belonging to the Bufonidae family. As a traditional Chinese medicine, its medicinal history is long, first recorded in the *Shennong Bencao Jing* (Shennong's Classic of Materia Medica), which describes it as having a "pungent taste, cool nature, and entering the heart, liver, spleen, and lung meridians. It treats pathogenic factors, breaks up blood stasis, dispels heat, promotes urination, and kills parasites." It can be used to treat carbuncles, boils, sores, ulcers, infantile malnutrition, oral ulcers, hemorrhoids, ascites, boils, and other ailments. Currently, the main medicinal toads in my country are the Chinese giant toad and the black-rimmed toad, widely distributed in Jiangsu, Shandong, Zhejiang, and other regions. The entire toad has medicinal value, with toad venom, dried toad, and toad skin being the most widely used core ingredients clinically. Their core medicinal effects include anti-tumor, local anesthesia, analgesia, and anti-inflammation.

[0003] Dried toad is the dried whole body of the Chinese giant toad or the black-rimmed toad after removing its internal organs, including skin and flesh. Although it has slight toxicity, it has the effects of reducing swelling, inflammation, and diuresis, and is suitable for the treatment of various diseases such as acne and chronic bronchitis. The Qing Dynasty book "Ciyou Bianlan" mentions: "For infantile malnutrition with a large belly, yellow and thin skin, scabs on the head, and hair like ears of wheat: take five dried toads, remove the four legs, apply sesame oil, roast until charred and grind into powder... take more, and the appearance will change naturally, and the disease will disappear"; "Zhengzhi Zhenjing" records: "For infantile malnutrition and diarrhea (with thin flesh, pale face, dry skin and hair standing on end), dried toad is used in tonifying and astringent prescriptions"; Wu Shangxian recorded in "Liyue Pianwen": "Toad ointment, dried toad, boiled in oil, with litharge and calomel, stirred with locust branches. Treats food stagnation, malnutrition, leg swelling, dampness, and sores."

[0004] Toads also play an important role in agricultural production and ecological protection, effectively eliminating agricultural pests, maintaining environmental hygiene, and reducing sources of infection. However, the mortality rate of toads during breeding is relatively high. Therefore, in-depth research on the medicinal resources of dried toads is of great significance for environmental protection and the development of traditional Chinese medicine.

[0005] However, due to factors such as changes in the ecological environment, excessive use of pesticides and fertilizers, and fragmentation of road networks, the habitat range of toads has shrunk significantly. Coupled with human overhunting and killing, wild toad resources have continued to decline and are now on the verge of depletion, leading to a year-on-year increase in the price of medicinal materials made from toads (such as toad skin and toad venom). Toad venom meeting the standards of the Chinese Pharmacopoeia sells for up to 85,000 yuan per kilogram, while toad venom with higher content sells for over 100,000 yuan per kilogram. In contrast, dried toads sell for only 50-80 yuan per kilogram. Therefore, large-scale toad farming has broad market prospects. Currently, the mortality rate of toad farming is over 70%. Utilizing dead toads to produce dried toads can effectively improve resource utilization. Currently, toads are mainly used in medicine for dried toads, toad skin, and toad venom. The bones, meat, and internal organs of toads after collecting venom and skinning are mostly discarded as waste, resulting in a huge waste of resources. If these wastes are used as raw materials to extract and process toad oil, it can turn waste into treasure. As a new resource for traditional Chinese medicine, toad oil has unique development potential. It can transform livestock waste into high-value-added products, thereby improving the efficiency of resource reuse.

[0006] Premature ejaculation (PE) is the most common ejaculatory dysfunction in men, with an incidence rate as high as 35%-50%. Epidemiological studies show that 75% of men will experience PE symptoms at some point in their lives. With the development of domestic society and the improvement of residents' living standards, people's demand for sexual health is increasing. In the past 30 years, women's sexual awareness has gradually increased, and more men are actively seeking medical help for ejaculation problems. However, the current clinical diagnostic system for premature ejaculation is still relatively backward.

[0007] The high stress, fast pace, and unhealthy lifestyles of contemporary society can easily lead to a decline in male sexual function and a shortened ejaculation time. Current oral medications suffer from long treatment courses and limited efficacy, while traditional Chinese medicine preparations also have drawbacks such as prolonged treatment duration, slow onset of action, and unsatisfactory results. Western medicine believes that premature ejaculation is mostly caused by psychological factors, with a few cases stemming from organic lesions. Existing medications for premature ejaculation caused by nervous hypersensitivity are mostly anesthetics, which reduce the sensitivity of the central nervous system by locally anesthetizing the male genitalia to achieve a delaying effect. However, these drugs can easily cause side effects such as burning sensation and numbness in the genital area, and long-term use may also lead to decreased libido and affect the health of the nervous system (CN 110151828 A). Although there are various treatment methods for premature ejaculation, including psychotherapy, behavioral training, antidepressant medication, and surgery, topical penile medications remain the mainstream clinical treatment due to their advantages of rapid onset of action, ease of use, high safety, and low cost. Studies have shown that topical penile medication can reduce local sensitivity, prolong ejaculation latency, and improve the quality of sexual life (Wei Changpeng, Xing Lubin, Gao Wenxi, et al. Clinical observation on the treatment of primary premature ejaculation with topical toad venom liniment [C] / / Chinese Association of Integrative Medicine, Andrology Committee. Proceedings and lecture notes of the 7th National Conference on Integrative Medicine and Andrology and the National Advanced Course on Integrative Medicine and Andrology. Department of Urology, Hubei Provincial Hospital of Traditional Chinese Medicine). For example, topical toad venom liniment has achieved certain clinical effects in the treatment of primary premature ejaculation. However, traditional liniments have obvious shortcomings. The dosage is difficult to control precisely, and most of them use ethanol as a solvent. Ethanol is volatile and will take away the moisture and oil on the skin surface. At the same time, the liquid is easy to flow, making it impossible to achieve precise application.

[0008] Medicated towel preparations are a newly emerging dosage form in the *Yang Sheng Fang* (Prescriptions for Nourishing Life), not seen in previous books, and appearing multiple times within the text. Medicated towel preparations involve soaking a cloth in medicinal liquid, which is then used as a poultice for external application. For example: "After four days, filter out the dregs and use the liquid to dye three feet of cloth. Dry in the shade, then dye again. The liquid is thin; wrap the cloth carefully, avoiding rough edges. Use a piece the size of your palm, insert it into the nostrils; it will cause slight itching and heat; apply it to the arm; it will cause large, firm, and hot itching." This method involves filtering the medicinal liquid to remove the dregs, using the liquid to dye three feet of cloth, drying it in the shade, and then repeating this process until the liquid is fully absorbed into the cloth. The medicated towel is then used either as a poultice or applied to the affected area to achieve a therapeutic effect. It involves permeating the cloth with the medicinal liquid before using it to treat the disease (Xu Xia. A Historical Study of Prescription Dosage Forms Before the Song Dynasty [D]. China Academy of Chinese Medical Sciences, 2010.). Summary of the Invention

[0009] This invention addresses the problems existing in the prior art by providing a topical wipe containing dried toad extract and toad oil. This topical wipe is effective in treating premature ejaculation and erectile dysfunction. This invention transforms toad oil from waste into a valuable resource while simultaneously improving the toad resource utilization system. Based on this, this invention was completed.

[0010] In a first aspect, the present invention provides a topical wipe containing the following raw materials in parts by weight: 1 part of ultrafine powdered dried toad extract and 3-8 parts of water-soluble toad oil.

[0011] Preferably, the towel contains the following raw materials in parts by weight: 1 part of ultrafine powdered dried toad extract and 4-7 parts of water-soluble toad oil.

[0012] More preferably, the towel contains the following raw materials in parts by weight: 1 part of ultrafine powdered dried toad extract and 5 parts of water-soluble toad oil.

[0013] The extraction process of the ultrafine powdered dried toad extract is as follows: S01 Dried toad powder is added to 95% ethanol at a material-to-liquid ratio of 1:10. Each extraction lasts 1-2 hours and is repeated 1-3 times. S02 is heated and refluxed through a reflux condenser, and the extract is collected. The residue is then extracted twice more, and the extracts are combined. S03 The obtained extract was concentrated under reduced pressure to obtain a dried toad extract.

[0014] S04 The above-mentioned dried toad extract is mixed with water at a material-liquid ratio of 1:1, soaked for 30 minutes, and continuously dried in a drying oven at 60°C until the water content is less than 5%. The dried toad extract is then pulverized through an 80-mesh pharmacopoeia sieve and pulverized through an air jet mill to obtain an ultrafine powder of dried toad extract with a mesh size of 800-2000.

[0015] Furthermore, in step S01, the preparation of the dried toad powder involves placing dried toads in a drying oven for continuous drying until the moisture content is less than 5%, pulverizing them with a pulverizer, and passing them through a 120-mesh pharmacopoeia sieve to obtain dried toad powder.

[0016] The preparation process of the water-soluble toad oil is as follows: S05 uses toad viscera as raw material. After crushing, heating and centrifuging, the resulting oil is filtered to obtain toad oil. S06 involves soaking toad oil in water to create a solution containing bloated substances; S07 pours the solution containing the swelling into a homogenizer to break down the connective tissue and cells, thus obtaining a suspension or colloidal homogenate; S08 involves ultrasonic treatment of suspensions or colloidal homogenates to break down cells and release their contents, resulting in a readily soluble, whole, emulsion-like water-soluble toad oil liquid.

[0017] Furthermore, in step S06, the ratio of toad oil to water is 1:10, and the mixture is soaked for 10 hours.

[0018] In a second aspect, the present invention provides a method for preparing the external wipes described in the first aspect, the method comprising the following steps: Preparation of S1 ultrafine powdered dried toad extract: S11 involves continuously drying the dried toad, pulverizing it, and then passing it through a 120-mesh pharmacopoeia sieve to obtain dried toad powder. S12 dried toad powder was added to 95% ethanol, heated under reflux using a reflux condenser, and the extract was collected. The residue was then extracted twice more, and the extracts were combined. S13 The extract obtained in the above steps is concentrated under reduced pressure to obtain dried toad extract; S14 The above-mentioned dried toad extract is soaked in water, continuously dried, pulverized and sieved, and the sieved dried toad extract is pulverized by an air jet mill to obtain ultrafine powdered dried toad extract.

[0019] Preparation of S2 water-soluble toad oil: S21 uses toad viscera as raw material. After crushing, heating and centrifuging, the resulting oil is filtered to obtain toad oil. S22 involves soaking toad oil in water to create a solution containing bloated substances; S23 pours the solution containing the swelling into a homogenizer to break down the connective tissue and cells, thus obtaining a suspension or colloidal homogenate; S24 involves sonicating suspensions or colloidal homogenates to break down cells and release their contents, resulting in a readily soluble, whole, emulsion-like water-soluble toad oil liquid.

[0020] Furthermore, in step S11, the moisture content of the dried toad powder is less than 5%.

[0021] Furthermore, in step S12, the ratio of the dried toad powder to 95% ethanol is 1:10, and the extraction is performed 1-3 times, with each extraction lasting 1-2 hours.

[0022] Further, in step S14, the ratio of the dried toad extract to water is 1:1, the mixture is soaked for 30 minutes, continuously dried in a drying oven at 60°C until the water content is less than 5%, pulverized through an 80-mesh pharmacopoeia sieve, and then pulverized by an air jet mill to obtain an ultrafine powder of dried toad extract with a mesh size of 800-2000.

[0023] Furthermore, in step S22, the ratio of toad oil to water is 1:10, and the mixture is soaked for 10 hours.

[0024] Preparation of S3 external wipes: S31 added ultrafine powdered dried toad extract to Transcutol P solvent and dissolved it by shaking at room temperature to obtain a dried toad extract solution.

[0025] S32 adds water-soluble toad oil, Labrasol, Plurol Oleique CC497, and water to a homogenization tank to obtain a toad oil dispersion.

[0026] S33 adds the dried toad extract solution to the toad oil dispersion, mixes evenly, and filters.

[0027] S34 involves placing the non-woven fabric in the obtained filtrate, soaking it for 3 hours, sterilizing and disinfecting it, and then sealing and packaging it to obtain a topical towel containing dried toad extract and toad oil.

[0028] Furthermore, in step S32, the homogenizing tank is set to conditions of 50°C, homogenization at 2000 r / min for 5 min, and cooling to below 30°C to obtain toad oil dispersion.

[0029] Thirdly, the present invention provides the application of a composition of ultrafine powdered dried toad extract and water-soluble toad oil in the preparation of a topical dressing for treating premature ejaculation and erectile dysfunction in men; the composition contains 1 part of ultrafine powdered dried toad extract and 3-8 parts of water-soluble toad oil.

[0030] Furthermore, the premature ejaculation includes primary premature ejaculation, secondary premature ejaculation, naturally occurring variant premature ejaculation, and subjective premature ejaculation.

[0031] Furthermore, primary premature ejaculation refers to a condition that has persisted since the first sexual experience and with all sexual partners, with IELT typically being extremely short (<1 minute).

[0032] Furthermore, the aforementioned secondary premature ejaculation refers to a condition in which the patient previously had normal ejaculatory control, but which subsequently develops due to some reason, with IELT significantly shortened to less than 3 minutes.

[0033] Furthermore, the aforementioned natural variant premature ejaculation refers to irregular, occasional premature ejaculation, which is not true premature ejaculation but a normal fluctuation in sexual function.

[0034] Furthermore, subjective premature ejaculation refers to a condition where the patient subjectively believes they have premature ejaculation, but their actual ejaculation time is within the normal or even longer range, and they are dissatisfied with their ejaculation time.

[0035] Furthermore, erectile dysfunction refers to a man's inability to maintain or achieve a sufficient penile erection to complete a satisfactory sexual intercourse.

[0036] The medicinal properties and effects of each Chinese medicinal herb in this invention are as follows: Dried toad: pungent, cool; poisonous. Enters the spleen, liver, and lung meridians. Breaks up lumps, eliminates infantile malnutrition, promotes urination, detoxifies, kills parasites, and relieves pain. Used for boils, carbuncles, edema, and infantile malnutrition.

[0037] Toad oil: pungent and warm; enters the heart and spleen meridians. It tonifies the kidneys and replenishes essence, nourishes yin and moistens the lungs, and is mainly used for physical weakness, post-illness recovery, fatigue, palpitations, and insomnia.

[0038] Beneficial effects This invention prepares a delay spray by controlling the dosage of dried toad extract and toad oil, which can be used to improve premature ejaculation and erectile dysfunction in men. The preparation has the advantages of direct action, precise dosage, individual packaging, and immediate use. Furthermore, it uses toads that have died during farming as raw materials, effectively controlling costs. By transforming the "waste" after toad venom extraction into the medicinal raw material of this invention (i.e., the dried toad of this invention refers to toads from which toad venom has been extracted), it greatly revitalizes resources idle in traditional processes, while simultaneously turning toad oil "waste into treasure," ensuring the full utilization of toads, and achieving "cost reduction and efficiency improvement, quality optimization," reducing the economic burden of drug production and clinical application. It possesses strong market competitiveness and broad promotional value, with a promising market prospect. Attached Figure Description

[0039] Figure 1 High-performance liquid chromatography (HPLC) spectrum of alcohol-extracted toad extract Figure 2 High-performance liquid chromatography (HPLC) spectrum of toad venom extract extracted with alcohol Figure 3 High-performance liquid chromatography (HPLC) spectrum of toad venom extracted with alcohol Detailed Implementation

[0040] The specific embodiments of the present invention will be further described below. It should be noted that these descriptions are for the purpose of aiding understanding the present invention, but do not constitute a limitation thereof. Furthermore, the technical features involved in the embodiments described below can be combined with each other as long as they do not conflict with each other.

[0041] Unless otherwise specified, the experimental methods used in the following embodiments are conventional methods, and the experimental materials used in the following embodiments are all available through conventional commercial channels.

[0042] Example 1: Preparation of a topical wipe containing dried toad extract and toad oil 1.1 Raw material preparation (1) Preparation of ultrafine powdered dried toad extract: a. The dried toad is continuously dried until its final moisture content is less than 5%, then pulverized and passed through a 120-mesh pharmacopoeia sieve to obtain dried toad powder; b. Add 95% ethanol to dried toad powder and extract 1-3 times at a material-to-liquid ratio of 1:10, each extraction lasting 1-2 hours; c. Heat the extract under reflux using a reflux condenser, collect the extract, extract the residue twice more, and combine the extracts. d. Concentrate the extract obtained in step (c) under reduced pressure to obtain dried toad extract. Weigh 5g of the dried toad extract for high-performance liquid chromatography (HPLC) analysis to determine its components. Figure 1 Chromatogram; e. Mix the dried toad extract obtained in step (d) with water at a material-to-liquid ratio of 1:1, soak for 30 minutes, continuously dry, pulverize through an 80-mesh pharmacopoeia sieve, and pulverize the sieved dried toad extract through an air jet mill to obtain an 800-2000 mesh ultrafine powder of dried toad extract.

[0043] (3) Preparation of water-soluble toad oil: a. Using toad viscera as raw material, the toad is crushed, heated, and centrifuged. The resulting oil is then filtered to obtain toad oil. b. Soak toad oil and water at a ratio of 1:10 at room temperature for 10 hours to obtain a solution containing the expanded substance; c. Pour the solution containing the swelling into a homogenizer to break down the connective tissue and cells, and obtain a suspension or colloidal homogenate; d. The suspension or colloidal homogenate is subjected to ultrasonic treatment to break down the cells and release the intracellular contents to obtain a readily soluble, whole, emulsion-like water-soluble toad oil.

[0044] 1.2 Preparation of external wipes a. Weigh 20g of the ultrafine powdered dried toad extract obtained in step 1.1(e) and add it to 180mL of Transcutol P solvent. Dissolve by shaking at room temperature to obtain an ultrafine powdered dried toad extract solution.

[0045] b. Add 100 mL of the water-soluble toad oil obtained in step 1.1 (d), 200 mL of Labrasol, 60 mL of Plurol Oleique CC497, and 440 mL of water to a homogenizing tank, heat to 50 °C, homogenize at 2000 r / min for 5 min, and cool to below 30 °C to obtain a toad oil dispersion.

[0046] c. Add the ultrafine powdered dried toad extract solution obtained in step (a) to the toad oil dispersion obtained in step (b), mix well, filter, and obtain the filtrate.

[0047] d. Place the nonwoven fabric in the filtrate obtained in step (c), soak for 3 hours, sterilize and disinfect, and then seal and package to obtain the external towel containing dried toad extract and toad oil.

[0048] Example 2: Preparation of Toad Venom External Application Towel 1.1 Preparation of toad venom extract: a. Take 1000g of toad venom and dry it at a temperature of 60℃ for 12-24 hours to make the final moisture content of the toad venom less than 5%, and obtain 920g of dried toad venom. b. Crush the dried toad venom into powder and pass it through an 80-mesh pharmacopoeia sieve; c. The dried toad venom powder and 95% ethanol were placed in a reaction vessel at a ratio of 1:20 and heated to 75°C. The reaction was carried out for 1 hour to obtain toad venom extract. d. The toad venom extract obtained in step (c) was concentrated under reduced pressure to obtain 376.25g of toad venom extract.

[0049] The obtained toad venom extract (5g) and toad venom (5g) were respectively analyzed by high performance liquid chromatography (HPLC) to determine their components. Figure 2 , Figure 3 Chromatogram.

[0050] 1.2 Determination of the content of toad venom and toad venom extract (1) Chromatographic conditions and system suitability test: Octadecylsilane-bonded silica gel was used as the packing material; acetonitrile was used as mobile phase A, and 0.3% acetic acid solution was used as mobile phase B, with gradient elution performed according to the specifications in the table below; the column temperature was 30℃; the flow rate was 0.6 mL per minute; and the detection wavelength was 296 nm. The theoretical plate number, calculated based on the bufotoxin base peak, should not be less than 10,000. (2) Preparation of reference solution: Take an appropriate amount of bufotoxin reference standard, accurately weigh it, add methanol to prepare a solution containing 100 μg per ml; (3) Preparation of test solution: Take 25 mg each of dried toad extract, toad venom powder and toad venom extract, weigh accurately, place in a stoppered conical flask, add 20 ml of methanol accurately, weigh, heat under reflux for 1 hour, cool, weigh again, make up the lost weight with methanol, shake well, filter, and take the filtrate to obtain the test solution. (4) Determination method: Accurately pipette 10 μl of the above reference solution and 10-20 μl of the test solution, respectively, and inject them into the liquid chromatograph for determination.

[0051] (5) The results are shown in the table below. Table 1. Content Determination Results 1.3 Preparation of external application of toad venom: a. Add 20g of toad venom extract to 3775mL of Transcutol P solvent and dissolve by shaking at room temperature to obtain toad venom extract solution.

[0052] b. Add 4190 mL of Labrasol, 1258 mL of Plurol Oleique CC497, and 11315 mL of water to a homogenizing tank, heat to 50°C, homogenize at 2000 r / min for 5 min, and cool to below 30°C to obtain an aqueous dispersion.

[0053] c. Add the toad venom extract solution obtained in step (a) to the aqueous dispersion obtained in step (b), mix well, filter, and obtain the filtrate.

[0054] d. Place the nonwoven fabric in the filtrate obtained in step (c), soak for 3 hours, sterilize and disinfect, and then seal and package to obtain the external towel containing toad venom.

[0055] Example 3 Preparation of Matrix Topical Towel a. Add 180 mL Transcutol P, 200 mL Labrasol, 60 mL Plurol Oleique CC497, and 560 mL water to a homogenizing tank, heat to 50 °C, homogenize at 2000 r / min for 5 min, cool to below 30 °C to obtain a matrix dispersion, filter, and obtain the filtrate; b. Place the nonwoven fabric in the obtained filtrate, soak for 3 hours, sterilize and disinfect, and then seal and package to obtain the external towel containing the matrix. Example 4 Clinical Study

[0056] 1. Method A randomized, double-blind study design was used to conduct standardized clinical efficacy verification of premature ejaculation and erectile dysfunction in men.

[0057] 2. Research Subjects This study selected 120 patients with premature ejaculation and 135 patients with erectile dysfunction recommended by the Chinese Sexology Association and the First Affiliated Hospital of Sun Yat-sen University. Based on the diagnostic criteria of both traditional Chinese and Western medicine, and the inclusion and exclusion criteria, 114 patients with premature ejaculation and 120 patients with erectile dysfunction were screened. They were randomly divided into a premature ejaculation control group and a medication group (Medication Group 1: toad venom group; Medication Group 2: dried toad extract + toad oil group), with 38 patients in each group; and an erectile dysfunction control group and a medication group (Medication Group 1: toad venom group; Medication Group 2: dried toad extract + toad oil group), with 40 patients in each group.

[0058] How to use (1) Preparation before use: Wash the penis, foreskin and coronal sulcus with warm water before use, and dry them to ensure that the skin is dry, undamaged and free of inflammation, so as to avoid the drug irritating the damaged skin; (2) Usage and dosage: The blank group patients used the base delay towel, the drug group 1 patients used the toad venom delay towel, and the drug group 2 patients used the dried toad extract and toad oil delay towel. Each of the three groups of patients took one of the prepared delay towels and applied it wet to the coronal sulcus, avoiding application to non-sensitive areas such as the urethral opening and scrotum to reduce irritation. (3) Onset time: After applying the wet compress, wait 15 minutes for the active ingredients to be fully absorbed, then wipe off any residue on the surface and avoid contact with the partner's mucous membrane; (4) Frequency of use: Use before sexual intercourse, avoid frequent use.

[0059] 4. Diagnostic criteria 4.1 Western Medicine Diagnostic Criteria Premature ejaculation is diagnosed according to the standard diagnosis in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders.

[0060] Primary premature ejaculation (IELT): This condition persists from the first sexual experience and with all sexual partners; the IELT is typically very short, less than 1 minute. It is often more related to physiological and neurobiological factors, and is relatively difficult to treat.

[0061] Secondary premature ejaculation: Previously, there was normal ejaculatory control, but it developed later for some reason, with IELT significantly shortened to less than 3 minutes. It may be caused by hyperthyroidism, prostatitis, psychological stress, poor marital relationship, etc.

[0062] Natural variant premature ejaculation: Irregular, occasional premature ejaculation is not true premature ejaculation, but a normal fluctuation in sexual function, and usually does not require medical intervention.

[0063] Subjective premature ejaculation: The patient subjectively believes they have premature ejaculation, but their actual ejaculation time (IELT) is within the normal or even longer range, and they are dissatisfied with the ejaculation time. This is mainly related to psychological factors, erroneous perceptions, or a mismatch between the expectations of the partner.

[0064] For erectile dysfunction, please refer to the 2018 edition of the "AUA Guidelines for the Diagnosis and Treatment of Erectile Dysfunction".

[0065] 1. The penis is unable to achieve or maintain a sufficient erection to complete satisfactory sexual intercourse under adequate sexual stimulation, with a course of illness ≥3 months.

[0066] 2. Disease grading criteria: The patient's condition is assessed according to the International Erectile Dysfunction Scale (IIEF-5): 22-25 points is normal, 17-21 points is mild dysfunction, 12-16 points is mild to moderate dysfunction, 8-11 points is moderate dysfunction, and 5-7 points is severe dysfunction.

[0067] 4.2 Traditional Chinese Medicine Diagnostic Criteria The TCM diagnostic criteria for premature ejaculation conform to the relevant diagnostic criteria in "Xu Fusong's Practical TCM Andrology" and "Clinical Guidelines for Andrology", and information is collected based on "inspection, auscultation, inquiry, and palpation".

[0068] Damp-heat in the Liver Meridian: Damp-heat in the Liver Meridian disturbs the seminal vesicle. Systemic symptoms: dizziness, bitter taste in the mouth, dry throat, irritability, dampness in the scrotum, and dark yellow urine. Tongue and pulse: red tongue, yellow and greasy coating, and wiry and rapid pulse.

[0069] Yin deficiency with exuberant fire: Kidney yin deficiency, internal disturbance of deficient fire, and scorching of the seminal vesicles. Systemic symptoms: Five-center heat (palms, soles, and chest), tidal fever and night sweats, soreness and weakness of the lower back and knees, dizziness and tinnitus. Tongue and pulse: Red tongue with little coating, thready and rapid pulse.

[0070] Kidney Qi Deficiency: Kidney Qi is deficient, its function of consolidating and retaining essence is impaired, and the seminal gate is not secure. Systemic Symptoms: Lower back and knee weakness, lethargy, pale complexion, frequent or clear urination. Tongue and Pulse: Pale tongue with white coating, deep and weak pulse. Heart and Spleen Deficiency: This condition involves depletion of heart blood, impaired spleen function, qi deficiency leading to sinking, and inability to retain essence. Systemic symptoms include insomnia with excessive dreaming, fatigue, pale complexion, poor appetite, abdominal distension, and loose stools. Tongue and pulse characteristics: Pale, swollen tongue with teeth marks, thin white coating, and weak, thready pulse.

[0071] Heart-Kidney Disharmony: Insufficient kidney water fails to nourish heart fire, leading to excessive heart fire that fails to warm kidney water. Systemic symptoms: Palpitations, dizziness, tinnitus, dry throat and mouth, lower back and knee weakness, night sweats, and hot flashes. Tongue and pulse: Red tongue with little coating, thready and rapid pulse.

[0072] The TCM diagnostic criteria for erectile dysfunction were formulated with reference to the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine (Trial Implementation)," "Traditional Chinese Medicine Andrology," and "Traditional Chinese Medicine Internal Medicine," combined with relevant content from this study, to establish the diagnostic criteria for kidney yang deficiency syndrome. Main symptom: Inability to maintain an erection during sexual intercourse.

[0073] Secondary symptoms: lower back and knee pain, dizziness and tinnitus, aversion to cold and cold limbs.

[0074] Tongue and pulse: The tongue is pale with a white coating, and the pulse is deep and thready.

[0075] If two or more of the primary and secondary symptoms are present, and the tongue and pulse are also considered, the diagnosis is confirmed as this syndrome type.

[0076] 4.3 Severity classification of the disease ① Mild: Ejaculation occurs within 2 minutes of penile insertion into the vagina; ② Moderate: Ejaculation occurs within one minute of penile insertion into the vagina; ③ Severe: Ejaculation occurs before or immediately after penetration.

[0077] 5. Inclusion and exclusion criteria: 5.1 Inclusion Criteria 1. Patients must be male, aged ≥18 years and ≤50 years. 2. Maintaining a single, stable sexual relationship with the same woman for at least 6 months; 3. Intravaginal ejaculation latency time: The time from penile insertion into the vagina to ejaculation, whether continuous or repeated, is less than 3 minutes; 4. Ejaculatory control: Always or almost always unable to delay ejaculation; 5. Negative consequences: Premature ejaculation can lead to negative personal consequences such as distress, anxiety, frustration, or avoidance of sexual intimacy. 6. Duration and frequency of symptoms: Symptoms persist for 6 months or more and occur in almost (75%-100%) or almost all sexual activities; 7. Meets the diagnostic criteria of both traditional Chinese medicine and Western medicine.

[0078] 5.2 Exclusion Criteria 1. Individuals with a history of significant comorbidities in various systems; 2. Those with other sexual dysfunctions, such as decreased libido, inhibited orgasm, or anejaculation; 3. The female partner has significant sexual dysfunction, such as sexual aversion, decreased libido, painful intercourse, orgasmic disorder, and others; 4. Penile deformity; 5. Acute and chronic inflammation of the reproductive system and sexually transmitted diseases; 6. Those allergic to alcohol or the selected traditional Chinese medicine; 7. Those with ulcers or other skin lesions on the foreskin and glans; 8. Homosexuals; 9. Individuals with a history of drug abuse or drug use within the past year; 10. Non-human factors: Premature ejaculation caused by factors other than one's own body, such as alcohol or drug abuse or withdrawal; 11. Partner's sexual problems: Sexual dysfunction in the partner (such as painful intercourse, vaginal dryness) is a major cause of premature ejaculation; 12. Other sexual dysfunctions: Erectile dysfunction that is a coexisting and primary problem; 13. Non-vaginal sexual activity: The standard only applies to vaginal intercourse and does not include premature ejaculation in other forms of sexual activity.

[0079] 6. Observation Indicators 6.1 Therapeutic indicators The effects of the dried toad extract and toad oil of this invention on male premature ejaculation and erectile dysfunction were evaluated using the CISFPE score (Chinese Premature Ejaculation Sexual Function Evaluation Scale), the Sexual Satisfaction Score (SSS, using scores of 6, 7, and 8 from 0 to 15 in the CISFPE score), and the International Index of Erectile Function (IIEF-5).

[0080] 6.2 Safety Indicators Complete blood count, urinalysis, liver function tests, and kidney function tests.

[0081] 6.3 Adverse Events Observe for any redness, swelling, pain, itching, rash, burning sensation, or erectile dysfunction due to penile numbness in the glans penis; also observe for any decreased vaginal sensation or discomfort in the woman.

[0082] 7. Statistical Analysis and Content Statistical analysis will be performed using SPSS 22.0 statistical analysis software. All inter-group statistical tests will be two-tailed, and a p-value less than or equal to 0.05 will be considered statistically significant. Chi-square tests will be used for categorical data, and continuous data will be expressed as mean ± standard deviation (x ± s). Paired-samples t-tests will be used for within-group comparisons, and independent-samples t-tests will be used for between-group comparisons. The rank-sum test will be used for comparing ordinal data. Pearson's correlation test will be used for correlation analysis.

[0083] 8. Results 8.1 Evaluation of premature ejaculation in patients Table 1. Evaluation Scale for Sexual Function in Chinese Patients with Premature Ejaculation (CISFPE Score) Note: * Compared with the blank control group, P < 0.05 As shown in Table 1, the sexual function of male patients was evaluated in terms of intravaginal ejaculation latency time, control of ejaculation time, and sexual satisfaction. The blank group had a low CISFPE score, indicating that they could not have normal sexual intercourse. Compared with the blank group, the toad venom group and the dried toad extract + toad oil group significantly improved male sexual dysfunction (P<0.05) and significantly improved female sexual satisfaction (P<0.05).

[0084] Table 2. Sexual satisfaction rating (SSS) Note: * Compared with the blank control group, P < 0.05 As shown in Table 2, when evaluating male patients' sexual function based on both male and female sexual satisfaction and the frequency of female orgasm, the blank group had low CISFPE scores, indicating an inability to engage in normal sexual intercourse. The toad venom group and the toad extract + toad oil group of this invention significantly improved sexual satisfaction (P < 0.05), indicating a good improvement effect on male premature ejaculation.

[0085] 8.2 Evaluation of Erectile Function Table 3 International Index of Erectile Function (IIEF-5) Note: * Compared with the blank control group, P < 0.05 As shown in Table 3, the patients' erectile function was evaluated using the International Index of Erectile Function (IIEF-5). The control group had moderate erectile dysfunction. The scores of the dried toad extract + toad oil group and the toad venom group after treatment were greater than or equal to 22 points, which is considered normal. Compared with the control group, the dried toad extract + toad oil group and the toad venom group of this invention have a significant effect on improving male erectile dysfunction (P < 0.05).

[0086] 8.3 Safety Index Measurement Results No significant abnormalities were found in blood routine tests, urine routine tests, liver function tests, and kidney function tests.

[0087] In the absence of penile lesions, there may be redness, swelling, pain, itching, rash, burning sensation of the glans penis, and erectile dysfunction due to penile numbness; in women, there may be no decreased vaginal sensation or vaginal discomfort.

Claims

1. A topical wipe, characterized in that, The topical wipe contains the following raw materials in parts by weight: 1 part of ultrafine powdered dried toad extract and 3-8 parts of water-soluble toad oil.

2. The external wipe as described in claim 1, characterized in that, The delay towel contains the following raw materials in parts by weight: 1 part of ultrafine powdered dried toad extract and 4-7 parts of water-soluble toad oil.

3. The external wipe as described in claim 1, characterized in that, The delay towel contains the following raw materials in parts by weight: 1 part of ultrafine powdered dried toad extract and 5 parts of water-soluble toad oil.

4. The external wipe as described in claim 1, characterized in that, The extraction process of the ultrafine powdered dried toad extract is as follows: S01 Dried toad powder is added to 95% ethanol at a material-to-liquid ratio of 1:

10. Each extraction lasts 1-2 hours and is repeated 1-3 times. S02 is heated and refluxed through a reflux condenser, and the extract is collected. The residue is then extracted twice more, and the extracts are combined. S03 The obtained extract was concentrated under reduced pressure to obtain a dried toad extract; S04 The above-mentioned dried toad extract is mixed with water at a material-liquid ratio of 1:1, soaked for 30 minutes, and continuously dried in a drying oven at 60°C until the water content is less than 5%. The dried toad extract is then pulverized through an 80-mesh pharmacopoeia sieve and pulverized through an air jet mill to obtain an ultrafine powder of dried toad extract with a mesh size of 800-2000.

5. The external wipe as described in claim 1, characterized in that, The preparation process of the water-soluble toad oil is as follows: S05 uses toad viscera as raw material. After crushing, heating and centrifuging, the resulting oil is filtered to obtain toad oil. S06 involves soaking toad oil in water to create a solution containing bloated substances; S07 pours the solution containing the swelling into a homogenizer to break down the connective tissue and cells, thus obtaining a suspension or colloidal homogenate; S08 involves ultrasonic treatment of suspensions or colloidal homogenates to break down cells and release their contents, resulting in a readily soluble, whole, emulsion-like water-soluble toad oil liquid.

6. The external wipe as described in claim 1, characterized in that, The dried toad powder is prepared by placing dried toads in a drying oven for continuous drying until the moisture content is less than 5%, pulverizing them with a pulverizer, and passing them through a 120-mesh pharmacopoeia sieve to obtain dried toad powder; the toad oil is soaked in water at a ratio of 1:10 for 10 hours.

7. A method for preparing the external wipe as described in claim 1, characterized in that, The preparation method of the external wipe includes the following steps: Preparation of S1 ultrafine powdered dried toad extract: S11 involves continuously drying the dried toad, pulverizing it, and then passing it through a 120-mesh pharmacopoeia sieve to obtain dried toad powder. S12 dried toad powder was added to 95% ethanol, heated under reflux using a reflux condenser, and the extract was collected. The residue was then extracted twice more, and the extracts were combined. S13 The extract obtained in the above steps is concentrated under reduced pressure to obtain dried toad extract; S14 Soak the above-mentioned dried toad extract in water, continuously dry it, pulverize and sieve it, and then pulverize the sieved dried toad extract through an air jet mill to obtain ultra-fine powdered dried toad extract. Preparation of S2 water-soluble toad oil: S21 uses toad viscera as raw material. After crushing, heating and centrifuging, the resulting oil is filtered to obtain toad oil. S22 involves soaking toad oil in water to create a solution containing bloated substances; S23 pours the solution containing the swelling into a homogenizer to break down the connective tissue and cells, thus obtaining a suspension or colloidal homogenate; S24 is used to sonicate suspensions or colloidal homogenates to break down cells and release intracellular contents to obtain a fast-dissolving, whole, emulsion-like water-soluble toad oil liquid. Preparation of S3 external wipes: S31 Add ultrafine powdered dried toad extract to Transcutol P solvent, and dissolve by shaking at room temperature to obtain dried toad extract solution; S32 adds water-soluble toad oil, Labrasol, Plurol Oleique CC497 and water into a homogenization tank to obtain a toad oil dispersion; S33 Add the dried toad extract solution to the toad oil dispersion, mix well, filter, and obtain the filtrate; S34 involves placing the non-woven fabric in the obtained filtrate, soaking it for 3 hours, sterilizing and disinfecting it, and then sealing and packaging it to obtain a topical towel containing dried toad extract and toad oil.

8. The method for preparing the external wipe as described in claim 7, characterized in that, In step S11, the moisture content of the dried toad powder is less than 5%; in step S12, the ratio of the dried toad powder to 95% ethanol is 1:10, and extraction is performed 1-3 times, each extraction lasting 1-2 hours; in step S14, the ratio of the dried toad extract to water is 1:1, and the extract is soaked for 30 minutes, continuously dried in a drying oven at 60°C until the moisture content is less than 5%, pulverized through an 80-mesh pharmacopoeia sieve, and then pulverized using an air jet mill to obtain an 800-2000 mesh ultrafine powder of dried toad extract; in step S22, the ratio of toad oil to water is 1:10, and the extract is soaked for 10 hours; in step S32, the homogenizing tank is set to 50°C, homogenized at 2000 r / min for 5 minutes, and then cooled to below 30°C to obtain a toad oil dispersion.

9. The use of the delay towel as described in claim 1 in the preparation of a treatment for premature ejaculation and erectile dysfunction in men, characterized in that... The towel contains the following raw materials in parts by weight: 1 part ultrafine powdered dried toad extract and 3-8 parts toad oil; the premature ejaculation includes primary premature ejaculation, secondary premature ejaculation, naturally occurring premature ejaculation, and subjective premature ejaculation; the erectile dysfunction refers to a man's inability to maintain or obtain a sufficient penile erection to complete a satisfactory sexual intercourse.

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