Pleurotus citrinopileatus and angelica dahurica hemorrhoid-eliminating

Abstract

The invention relates to the field of traditional Chinese medicine compositions, in particular to a bitter-angelica hemorrhoid-eliminating ointment which is mainly prepared from the following raw materials in parts by weight: 30-50 parts of radix sophorae flavescentis, 20-30 parts of radix angelicae, 20-30 parts of sanguisorba officinalis, 15-25 parts of cacumen biotae, 15-25 parts of gallnut and 5-10 parts of borneol. According to the invention, through reasonable medicine compatibility, the medicines play a synergistic effect, an extraction process adopts a water extraction and alcohol precipitation combined method, the extraction rate and purity of effective components are improved, and the ointment contains more active components, so that the treatment effect of the medicines is enhanced. In the preparation forming process, the quality of the paste is ensured by accurately controlling parameters such as temperature and time.

Description

Technical Field

[0001] The invention relates to the technical field of Chinese medicine pharmaceutical preparation, and in particular to an external Chinese medicine ointment for treating hemorrhoids, including symptoms such as blood in stool, pain, swelling, prolapse and the like caused by internal hemorrhoids, external hemorrhoids, mixed hemorrhoids and the like, and a preparation method thereof. Background Art

[0002] Hemorrhoids are a common anorectal disease, and their incidence is on the rise worldwide. Long-term sitting, bad eating habits, constipation and other factors may induce hemorrhoids. At present, there are various methods for treating hemorrhoids clinically, including surgical treatment, drug treatment and the like. Although surgical treatment can directly remove hemorrhoids, there are problems such as large surgical trauma, obvious postoperative pain, long recovery time, and easy recurrence, which bring great pain and economic burden to patients. In terms of drug treatment, Western medicine mainly consists of local suppositories and ointments, such as ointments containing lidocaine and other ingredients. Its main function is to relieve pain, and the effect of improving symptoms such as shrinkage of hemorrhoids and blood in the stool is limited, and long-term use may cause adverse reactions such as local allergies. Oral Western medicines such as diosmin can improve venous return, but may also have side effects such as gastrointestinal discomfort. Traditional Chinese medicine has a long history and rich experience in treating hemorrhoids. It regulates the body's qi and blood circulation and viscera functions as a whole through its multiple functions such as clearing away heat and detoxifying, promoting blood circulation and removing blood stasis, reducing swelling and relieving pain, astringing and stopping bleeding, etc. It has the advantages of definite efficacy, few side effects, and low recurrence. However, existing traditional Chinese medicine external preparations still have some shortcomings in treating hemorrhoids.

[0003] The formulation of some traditional Chinese medicine compound prescriptions is not precise enough, and the synergistic effect between drugs has not been fully exerted. Although some prescriptions contain a variety of drugs with hemostatic, analgesic, and detumescent effects, the dosage ratio of each drug is not reasonable, resulting in unsatisfactory overall efficacy. For example, the ratio of heat-clearing drugs to blood-activating and stasis-removing drugs in some prescriptions is unbalanced. During the treatment process, excessive heat-clearing and insufficient blood-activating and stasis-removing drugs may occur, making it impossible to effectively eliminate hemorrhoids, or excessive blood-activating and stasis-removing drugs may not clear enough heat, making it difficult for local inflammation to subside.

[0004] The specificity of the different symptoms and syndromes of hemorrhoids is not strong. The symptoms and causes of hemorrhoids may vary from patient to patient. For example, some patients mainly suffer from internal hemorrhoid bleeding, while others suffer from external hemorrhoid pain and swelling. However, some existing Chinese medicine preparations cannot provide targeted treatment according to specific symptoms, and there are certain limitations in clinical application.

[0005] There are many problems in the raw material processing link. The quality of Chinese herbal medicines varies greatly, and the content of active ingredients in different origins and batches varies greatly. In the processing process, there is a lack of unified and strict standard operating procedures, which affects the efficacy and quality stability of the medicine. For example, different processing methods of Sophora flavescens may lead to changes in the content of its alkaloids and other active ingredients, which in turn affects the therapeutic effect of the ointment.

[0006] The extraction process is rough, and in most cases, a simple water extraction or alcohol extraction process is used, which has low extraction efficiency and cannot fully extract the active ingredients in the drug. This makes the content of active ingredients in the ointment insufficient, affecting the therapeutic effect. Patients need to use it for a long time to achieve a certain therapeutic effect, which increases the patient's treatment cost and time cost.

[0007] The preparation molding process is backward, and the traditional ointment production process is difficult to accurately control the fineness, stability, permeability, etc. of the ointment. The roughness of the ointment may affect the application and absorption of the drug, poor stability may easily lead to drug deterioration, and poor permeability may prevent the drug from effectively reaching the lesion site to exert its effect.

[0008] The packaging process is simple and lacks good sealing and moisture-proof measures. During storage, Chinese medicine pastes are easily affected by environmental factors such as air and humidity, which can cause oxidation, degradation or deterioration of the active ingredients, reducing the quality and efficacy of the medicine.

[0009] In summary, developing a Chinese medicine hemorrhoid-eliminating ointment with a reasonable drug formula and scientific preparation process is of great significance for improving the therapeutic effect of hemorrhoids. The Kuzhi Xiaozhi ointment of the present invention is an innovative Chinese medicine preparation developed based on these needs. Summary of the invention

[0010] The present invention aims to provide a Chinese medicine ointment with significant efficacy, convenient use and small side effects, which is used to treat various types of hemorrhoids, can quickly relieve the symptoms of pain, bleeding, swelling and the like caused by hemorrhoids, promote the shrinkage and healing of hemorrhoids, improve the therapeutic effect of the medicine, reduce the recurrence rate and improve the quality of life of patients through reasonable drug compatibility and scientific preparation process. A Kuzhi Xiaozhi ointment is mainly made of the following raw materials in parts by weight: 30-50 parts of Sophora flavescens, 20-30 parts of Angelica dahurica, 20-30 parts of Sanguisorba officinalis, 15-25 parts of Platycladus orientalis leaves, 15-25 parts of Galla chinensis, 5-10 parts of Borneolum, and an appropriate amount of Vaseline. Further, the Sophora flavescens is a monarch drug, which is cold in nature, bitter in taste, and enters the heart, liver, stomach, large intestine and bladder meridians, has the effects of clearing heat and dampness, killing insects and diuresis, contains a variety of alkaloids, such as matrine, oxymatrine, etc., has antibacterial, anti-inflammatory, anti-tumor, anti-allergic and other effects, and is suitable for damp-heat hemorrhoids.

[0011] Furthermore, the angelica dahurica and the radix sanguisorbae are ministerial drugs. The angelica dahurica is warm in nature, pungent in taste, and enters the lung, spleen, and stomach meridians. It has the effects of dispelling cold, dispelling wind and relieving pain, clearing the nasal passages, drying dampness and stopping leukorrhea, and reducing swelling and discharging pus. It can promote local blood circulation, enhance drug penetration, and help other drugs reach the lesion site. Its swelling and pus discharging effect is helpful for the dissipation of hemorrhoids. The radix sanguisorbae is cold in nature, bitter, sour, and astringent in taste, and enters the liver and large intestine meridians. It has the effects of cooling blood and stopping bleeding, detoxifying and astringing sores, and has a good therapeutic effect on bloody stools caused by hemorrhoids. Its detoxifying and astringing sores effect is helpful for promoting the healing of hemorrhoid wounds.

[0012] Furthermore, the Platycladus orientalis leaves and Galla chinensis are adjuvants. The Platycladus orientalis leaves are cold in nature, bitter in taste, and enter the lung, liver, and spleen meridians. They have the effects of cooling blood and stopping bleeding, resolving phlegm and relieving cough, and promoting hair growth and blackening hair. They can enhance the hemostatic effect and cooperate with the Radix Sanguisorbae to reduce hemorrhoidal bleeding. The Galla chinensis is cold in nature, sour and astringent in taste, and enters the lung, large intestine, and kidney meridians. It has the effects of astringing the lung and reducing fire, astringing the intestine and stopping diarrhea, astringing sweat and stopping bleeding, and astringing dampness and astringing sores. It can astringe and regenerate muscles, and promote the repair of hemorrhoidal mucosa. Its astringent and antidiarrheal effect can relieve the symptoms of anal swelling, frequent bowel movements, and the like caused by hemorrhoids.

[0013] Furthermore, the borneol is a guiding drug, which is slightly cold in nature, pungent and bitter in taste, and enters the heart, spleen, and lung meridians. It has the effects of invigorating the mind, clearing away heat and relieving pain, can promote transdermal absorption of drugs, and enhance the efficacy of other drugs. Its heat-clearing and analgesic effect can quickly relieve the symptoms of hemorrhoidal pain.

[0014] The present invention also provides a preparation method of the Kuzhi Xiaozhi ointment, comprising the following steps:

[0015] 1. Raw material pretreatment: Strictly identify and inspect each medicinal material in accordance with the "Chinese Pharmacopoeia" or local processing specifications. Remove impurities from Sophora flavescens, wash, moisten, slice, and dry; remove impurities from Angelica dahurica, wash, moisten, cut into thick slices, and dry; remove impurities from Sanguisorba officinalis, wash, moisten, slice, and dry; remove hard stems and impurities from Platycladus orientalis leaves, and dry in the shade or in the sun; crack open Galla chinensis and remove impurities; grind borneol into fine powder for use; select Chinese herbal medicine pieces that meet national drug standards for feeding;

[0016] 2. Extraction process: Take Sophora flavescens, Angelica dahurica, Sanguisorba officinalis, Platycladus orientalis leaves, and Galla chinensis, add 8-10 times the total weight of the medicinal materials in water, soak for 1-2 hours, then heat and decoct for 2-3 times, each time for 1-2 hours, combine the decoctions, filter, obtain a filtrate, decompress the filtrate to a clear paste with a relative density of 1.05-1.10 (60°C), then add ethanol to make the alcohol content reach 60%-70%, let it stand for 24-48 hours, take the supernatant, recover the ethanol and concentrate it to an extract with a relative density of 1.20-1.25 (60°C);

[0017] 3. Preparation molding process: Add borneol powder to the above extract, stir evenly to obtain a mixture, take an appropriate amount of vaseline and heat to melt, slowly add the mixture to the molten vaseline, stir evenly, continue to heat to 70-80°C, keep for 10-20 minutes to allow the paste to fully blend, then pour into a sterile container while hot, cool to room temperature, and obtain Kuzhi Xiaozhi Ointment.

[0018] Beneficial Effects

[0019] 1. Synergistic effect of drug combination

[0020] The present invention uses reasonable drug compatibility to make each drug play a synergistic effect. Sophora flavescens is the main drug for clearing away heat and drying dampness, while Angelica dahurica and Radix Sanguisorbae assist in enhancing the effects of detumescence and analgesia, hemostasis and sore astringency, Platycladus orientalis and Galla chinensis further cooperate in hemostasis, astringency and granulation, and Borneol promotes transdermal absorption and analgesia. All drugs are used together to act on the pathological mechanism of hemorrhoids from multiple aspects such as clearing heat, relieving pain, hemostasis, detumescence and granulation, comprehensively improve hemorrhoidal symptoms, improve cure rate and reduce recurrence rate. For example, Sophora flavescens is compatible with Angelica dahurica, one clears away heat and one promotes blood circulation, which enhances the improvement effect on local qi and blood stasis and damp-heat accumulation of hemorrhoids; Radix Sanguisorbae and Platycladus orientalis cooperate in hemostasis, making the hemostatic effect more remarkable.

[0021] 2. Preparation process optimization to improve drug quality and efficacy

[0022] The pretreatment of raw materials strictly follows the standard specifications to ensure the stability and reliability of the quality of the medicinal materials and provide high-quality raw materials for subsequent production. The extraction process adopts a combination of water extraction and alcohol precipitation to improve the extraction rate and purity of the effective ingredients, so that the ointment contains more active ingredients, thereby enhancing the therapeutic effect of the drug. In the preparation molding process, the quality of the paste is ensured by precise control of parameters such as temperature and time. The appropriate temperature and time make the paste delicate and uniform, easy to apply and absorb, and improve the bioavailability of the drug; the selection of vaseline matrix not only ensures the stability of the ointment, but also facilitates the adhesion and penetration of the drug in the lesion site, prolonging the drug action time. The strict quality control system ensures the stability and safety of the product quality, so that patients can use it with confidence. DETAILED DESCRIPTION

[0023] Embodiment 1: Kuzhi Xiaozhi ointment complete formula

[0024] 1. Raw material preparation and preparation of formulations

[0025] 1. Accurately weigh 40g of Sophora flavescens, 25g of Angelica dahurica, 25g of Sanguisorba officinalis, 20g of Platycladus orientalis, 20g of Galla chinensis, and 8g of Borneol.

[0026] All raw materials are Chinese herbal medicines that meet national pharmaceutical standards.

[0027] 2. Prepare and process each raw material: remove impurities from Sophora flavescens, wash, moisten, slice and dry; remove impurities from Angelica dahurica, wash, moisten, cut into thick slices and dry; remove impurities from Sanguisorba officinalis, wash, moisten, slice and dry; remove hard stems and impurities from Platycladus orientalis leaves, dry in the shade or in the sun; crack open Gallnut and remove impurities; grind borneol into fine powder for later use.

[0028] 3. Extraction process: Take Sophora flavescens, Angelica dahurica, Radix Sanguisorbae, Platycladus orientalis, and Galla chinensis, add 9 times the total weight of the medicinal materials in water, soak for 1.5 hours, then heat and decoct for 2 times, each time for 1.5 hours, combine the decoctions, filter, and obtain a filtrate. The filtrate is concentrated under reduced pressure to a clear paste with a relative density of 1.08 (60° C.), then ethanol is added to make the alcohol content reach 65%, and the mixture is allowed to stand for 36 hours, the supernatant is taken, the ethanol is recovered and concentrated to an extract with a relative density of 1.22 (60° C.).

[0029] 4. Preparation molding: Add borneol powder to the above extract, stir evenly to obtain a mixture. Take an appropriate amount of vaseline and heat it to melt, slowly add the mixture to the melted vaseline, stir evenly, continue to heat to 75°C, keep for 15 minutes, so that the paste is fully integrated, then pour it into a sterile container while hot, and cool it to room temperature to obtain Kuzhi Xiaozhi Ointment.

[0030] 2. Clinical application and effect observation

[0031] 1. 100 patients with hemorrhoids were selected, including 40 cases of internal hemorrhoids, 35 cases of external hemorrhoids, and 25 cases of mixed hemorrhoids. The age of the patients ranged from 25 to 60 years old, with an average age of (42±8) years old. The main symptoms included blood in the stool (mainly in patients with internal hemorrhoids), pain (mainly in patients with external hemorrhoids and mixed hemorrhoids), swelling, prolapse, etc., and the duration of the disease varied (1 month to 5 years, with an average course of 1.5 years).

[0032] 2. Dosage method: After the patient cleans the anus, apply an appropriate amount of Kuzhi Xiaozhi Ointment to the affected area, 2-3 times a day, and the course of treatment is 1-2 weeks (depending on the severity of the disease).

[0033] 3. Observation indicators

[0034] 1. Symptom improvement: record in detail the changes in the patient's bloody stools, pain, swelling, prolapse, etc.

[0035] The severity of the symptoms was scored (no symptoms = 0, mild symptoms = 1, moderate symptoms = 2,

[0036] Severe was 3 points), and the changes in symptom scores before and after treatment were calculated. The results showed that the symptom scores of patients were significantly reduced after treatment, and the total effective rate reached 85%. For example, the average score of blood in stool before treatment was 1.5±0.5 points, which dropped to 0.3±0.2 points after treatment; the average score of pain symptoms before treatment was 1.8±0.4 points, which dropped to 0.4±0.2 points after treatment; the average score of swelling symptoms before treatment was 1.6±0.4 points, which dropped to 0.3±0.2 points after treatment; the average score of prolapse symptoms before treatment was 1.2±0.3 points, which dropped to 0.2±0.1 points after treatment.

[0037] 2. Changes in hemorrhoid size: Measure the size of hemorrhoids before and after treatment through digital anal examination or proctoscopy.

[0038] After treatment, the hemorrhoids of patients with internal hemorrhoids and mixed hemorrhoids were significantly reduced, with an average reduction rate of more than 50%.

[0039] 3. Wound healing: For patients with anal fissures or external hemorrhoids, the wound healing time was observed. The wound healing time was significantly shortened after treatment, with an average healing time of (7±2) days.

[0040] 4. Safety index detection: The blood routine, liver and kidney function and other indicators of the patients were tested before and after treatment to observe the safety of the drug. The results showed that there was no significant change in the blood routine, liver and kidney function and other indicators of the patients before and after treatment, indicating that the drug was safe.

[0041] Example 2: Deficiency of Sophora flavescens (comparison of unilateral deficiency)

[0042] 1. Raw material preparation and preparation of formulations

[0043] 1. Weigh 25 g of Angelica dahurica, 25 g of Sanguisorba officinalis, 20 g of Platycladus orientalis, 20 g of Galla chinensis, and 8 g of Borneolum Syntheticum, and prepare them into a paste according to the extraction and preparation steps in Example 1.

[0044] 2. Clinical application and effect observation

[0045] 1. 100 patients similar to those in Example 1 were selected, with basically the same age, condition, etc., and the same administration method and observation indicators were used for treatment and observation.

[0046] 2. Symptom improvement: Although the symptom scores of patients were reduced to a certain extent after treatment, the total effective rate was only 45%, which was significantly lower than that of Example 1. The average score of blood in stool after treatment was 1.0±0.4 points, the average score of pain after treatment was 1.3±0.3 points, the average score of swelling after treatment was 1.1±0.3 points, and the average score of prolapse after treatment was 0.8±0.2 points, all of which were higher than the corresponding scores after treatment in Example 1.

[0047] 3. Changes in hemorrhoid size: The size of hemorrhoids does not shrink significantly, with an average shrinkage rate of less than 20%.

[0048] 4. Wound healing: The wound healing time is relatively long, with an average healing time of (12±3) days.

[0049] 5. Safety index testing: No obvious adverse reactions were found, but the overall treatment effect was poor.

[0050] Example 3: Lack of Angelica dahurica (comparison of single prescription deficiency)

[0051] 1. Raw material preparation and preparation of formulations

[0052] 1. Take 40g of Sophora flavescens, 25g of Sanguisorba officinalis, 20g of Platycladus orientalis, 20g of Galla chinensis, and 8g of Borneol to prepare an ointment, following the same steps as in Example 1.

[0053] 2. Clinical application and effect observation

[0054] 1. Select 100 eligible patients and give them the same treatment and observation.

[0055] 2. Symptom improvement: The total effective rate was 50%. The improvement of blood in stool, pain, swelling, prolapse and other symptoms was not as good as that in Example 1. After treatment, the average score of blood in stool was 1.2±0.4 points, and the average score of pain was 1.5

[0056] ±0.4 points, the average score of swelling symptoms was 1.3±0.3 points, and the average score of prolapse symptoms was 1.0±0.3 points.

[0057] 3. Change in hemorrhoid size: The hemorrhoid reduction rate was about 30%, which was lower than that in Example 1.

[0058] 4. Wound healing: The average healing time was (10±2) days, which was longer than that in Example 1.

[0059] 5. Safety indicator testing: Patients tolerated the drug well, but the treatment effect was limited.

[0060] Example 4: Sanguisorba officinalis deficiency (comparison of unilateral deficiency)

[0061] 1. Raw material preparation and preparation of formulations

[0062] 1. Prepare 40g of Sophora flavescens, 25g of Angelica dahurica, 20g of Platycladus orientalis, 20g of Galla chinensis, and 8g of Borneol, and make an ointment according to the process of Example 1.

[0063] 2. Clinical application and effect observation

[0064] 1. Select 100 patients and treat and observe according to Example 1.

[0065] 2. Symptom improvement: The total effective rate was 55%, and the reduction in symptom scores was limited. The average score after treatment of blood in stool was 1.1±0.3 points, the average score after treatment of pain was 1.4±0.3 points, the average score after treatment of swelling was 1.2±0.3 points, and the average score after treatment of prolapse was 0.9±0.2 points.

[0066] 3. Changes in hemorrhoid size: Hemorrhoids generally shrink to a moderate degree, with an average shrinkage rate of about 35%.

[0067] 4. Wound healing: The average healing time was (9±2) days, which was still slower than the healing speed of Example 1.

[0068] 5. Safety index testing: No special adverse reactions occurred, but the treatment effect needs to be improved.

[0069] Example 5: Lack of Platycladus orientalis leaves (unilateral lack comparison)

[0070] 1. Raw material preparation and preparation of formulations

[0071] 1. Weigh 40g of Sophora flavescens, 25g of Angelica dahurica, 25g of Sanguisorba officinalis, 20g of Galla chinensis, and 8g of Borneol to make a paste.

[0072] 2. Clinical application and effect observation

[0073] 1. 100 patients were selected as the research subjects.

[0074] 2. Symptom improvement: The total effective rate was 60%. The average score after treatment of blood in stool was 1.0±0.3 points, the average score after treatment of pain was 1.3±0.3 points, the average score after treatment of swelling was 1.1±0.3 points, and the average score after treatment of prolapse was 0.8±0.2 points.

[0075] 3. Change in hemorrhoid size: The hemorrhoid reduction rate is about 40%, which is a certain improvement but not as good as the complete formula.

[0076] 4. Wound healing: The average healing time was (8±2) days.

[0077] 5. Safety index detection: No obvious abnormalities were found, and the drug safety is relatively good. However, compared with the complete formula, there is still room for improvement in some aspects.

[0078] Example 6: Galla chinensis deficiency (unilateral deficiency comparison)

[0079] 1. Raw material preparation and preparation of formulations

[0080] 1. Take 40g of Sophora flavescens, 25g of Angelica dahurica, 25g of Sanguisorba officinalis, 20g of Platycladus orientalis leaves, and 8g of Borneol to prepare an ointment.

[0081] 2. Clinical application and effect observation

[0082] 1. Select 100 patients for treatment and observation.

[0083] 2. Symptom improvement: The total effective rate was 62%. The average score after treatment of blood in stool was 0.9±0.3 points, the average score after treatment of pain was 1.2±0.3 points, the average score after treatment of swelling was 1.0±0.3 points, and the average score after treatment of prolapse was 0.7±0.2 points.

[0084] 3. Changes in hemorrhoid size: The hemorrhoid reduction rate is about 42%.

[0085] 4. Wound healing: The average healing time was (7.5±1.5) days.

[0086] 5. Safety index detection: No adverse reactions were observed, but the therapeutic effect was not as ideal as the complete formula.

[0087] Example 7: Lack of Borneol (comparison of unilateral lack of Borneol)

[0088] 1. Raw material preparation and preparation of formulations

[0089] 1. Weigh 40g of Sophora flavescens, 25g of Angelica dahurica, 25g of Sanguisorba officinalis, 20g of Platycladus orientalis leaves, and 20g of Galla chinensis to make an ointment. The process is the same as that in Example 1 but without adding borneol.

[0090] 2. Clinical application and effect observation

[0091] 1. Conduct treatment observation on 100 patients.

[0092] 2. Symptom improvement: The total effective rate was 58%. The average score after treatment of blood in stool was 1.1±0.3 points, the average score after treatment of pain was 1.4±0.3 points, the average score after treatment of swelling was 1.2±0.3 points, and the average score after treatment of prolapse was 0.9±0.2 points.

[0093] 3. Changes in hemorrhoid size: The hemorrhoid reduction rate is about 38%.

[0094] 4. Wound healing: The average healing time was (9.5±2.5) days.

[0095] 5. Safety index detection: There were no obvious adverse events, but the drug transdermal absorption and analgesic effects were significantly weakened, affecting the therapeutic effect.

[0096] Example 8: Changing the number of extractions (process adjustment comparison)

[0097] 1. Raw material preparation and preparation of formulations

[0098] 1. According to the prescription, accurately weigh 40g of Sophora flavescens, 25g of Angelica dahurica, 25g of Sanguisorba officinalis, 20g of Platycladus orientalis, 20g of Galla chinensis, and 8g of Borneol. After pre-treatment, take Sophora flavescens, Angelica dahurica, Sanguisorba officinalis, Platycladus orientalis, and Galla chinensis, add 9 times the total weight of the medicinal materials in water, soak for 1.5 hours, then heat and decoct once, the decoction time is 2 hours, and the subsequent extraction and preparation molding steps are the same as Example 1.

[0099] 2. Clinical application and effect observation

[0100] 1. 100 patients were selected and the ointment after the adjustment process was used. The application method was the same as that in Example 1, and the course of treatment was 1-2 weeks.

[0101] 2. Symptom improvement: The total effective rate was 70%. The average score after treatment of blood in stool was 0.8±0.3 points, the average score after treatment of pain was 1.1±0.3 points, the average score after treatment of swelling was 0.9±0.3 points, and the average score after treatment of prolapse was 0.6±0.2 points.

[0102] 3. Changes in hemorrhoid size: The average reduction rate of hemorrhoids is about 45%.

[0103] 4. Wound healing: The average healing time was (7.2±1.8) days.

[0104] 5. Safety index detection: No obvious adverse reactions were found. After reducing the number of extractions, the extraction of the effective ingredients may not be complete. Although there is still a certain therapeutic effect, the overall effect is not as good as that in Example 1, indicating that the setting of the original number of extractions is of great significance to ensuring the efficacy of the drug.

[0105] 1. Invention of drug combination

[0106] (I) Overall synergy and efficiency

[0107] 1. Excellent therapeutic effect of the complete formula of Example 1

[0108] 1. The complete formula of Kuzhi Xiaozhi ointment in Example 1 (40g of Sophora flavescens, 25g of Angelica dahurica, 25g of Radix Sanguisorbae, 20g of Platycladus orientalis, 20g of Galla chinensis, and 8g of Borneolum Syntheticum) shows a remarkable effect in the treatment of hemorrhoids. Through the rational compatibility of multiple Chinese medicines, the symptoms of hemorrhoids such as blood in the stool, pain, swelling, and prolapse are fully exerted. As in clinical applications, the total effective rate after treatment is as high as 85%, the average score of blood in the stool is reduced from 1.5±0.5 points to 0.3±0.2 points, the pain symptom is reduced from 1.8±0.4 points to 0.4±0.2 points, the swelling symptom is reduced from 1.6±0.4 points to 0.3±0.2 points, the prolapse symptom is reduced from 1.2±0.3 points to 0.2±0.1 points, the average reduction rate of hemorrhoids in patients with internal hemorrhoids and mixed hemorrhoids reaches more than 50%, and the average healing time of patients with wound surface is (7±2) days, and there is no obvious effect on the patient's blood routine, liver and kidney function, etc., and the safety is good. This shows that the drugs work synergistically to regulate the body's Qi and blood, clear away heat and dampness, stop bleeding and relieve pain, astringe and regenerate tissue, and effectively improve the condition of hemorrhoids.

[0109] 2. The lack of a single side highlights the synergy

[0110] 1. The comparative tests of Examples 2-7, each lacking one drug, clearly show the importance of each drug in the formula. When Sophora flavescens (Example 2) is missing, the total effective rate is only 45%, the reduction in the symptom scores of blood in stool and pain is small, the hemorrhoids are not significantly reduced, and the wound healing time is long; when Angelica dahurica (Example 3) is missing, the total effective rate is 50%, the symptom improvement is not good, the hemorrhoid reduction rate is low, and the wound healing is slow; when Sanguisorba officinalis (Example 4) is missing, the total effective rate is 55%, the symptom score decreases limitedly, the hemorrhoids are generally reduced, and the healing time is long; when Platycladus orientalis leaves are missing (Example 5), the total effective rate is 60%, and the hemorrhoid reduction rate is about 40%, which is somewhat improved but not as good as the complete formula;

[0111] The total effective rate of the formula lacking gallnut (Example 6) is 62%, and the symptoms are improved and the hemorrhoids are reduced to a certain extent, but it is still not as good as the complete formula; the total effective rate of the formula lacking borneol (Example 7) is 58%, and the drug transdermal absorption and analgesic effect are significantly weakened. These results fully illustrate that the various drugs in the formula cooperate with each other, and none of them can be missing, and together they constitute a synergistic whole. The lack of any one drug will affect the overall therapeutic effect, thereby reflecting the scientificity and rationality of the formula compatibility.

[0112] (II) Complementary efficacy of drugs

[0113] 1. Use both heat-clearing and dampness-drying and blood-activating and blood-stasis-removing

[0114] 1. Sophora flavescens is the main drug for clearing away heat and drying dampness, while Angelica dahurica is the auxiliary drug for promoting blood circulation and reducing swelling, and the two complement each other. In Example 1, the two act together on the pathological link of damp-heat stagnation of hemorrhoids, so that local inflammation is alleviated, and swelling and pain are relieved. Compared with the situation of lacking Sophora flavescens (Example 2) or lacking Angelica dahurica (Example 3), the complete formula can better promote local blood circulation while clearing away heat and drying dampness, enhance the penetration and absorption of drugs, and accelerate the recovery of hemorrhoids. For example, in clinical observation, the improvement of swelling symptoms in patients in Example 1 is significantly better than that in the group lacking drugs, indicating that the compatibility of Sophora flavescens and Angelica dahurica is of great significance in eliminating swelling.

[0115] 2. Synergistic effect of hemostasis and sore healing

[0116] 1. Sanguisorba officinalis, Platycladus orientalis leaf and Chinese nut Galla chinensis play a synergistic role in hemostasis and sore astringency. Sanguisorba officinalis cools blood to stop bleeding, detoxifies and astringes sores, Platycladus orientalis leaf cools blood to stop bleeding, and Chinese nut Galla chinensis astringes and promotes tissue regeneration. In Example 1, the three work together to effectively control the symptoms of blood in the stool and accelerate wound healing. For example, the symptom score of blood in the stool is significantly reduced after treatment, and the wound healing time is shortened. However, when Sanguisorba officinalis (Example 4), Platycladus orientalis leaf (Example 5) or Chinese nut Galla chinensis (Example 6) are lacking, the hemostasis and sore astringency effects are not as good as the complete formula, which further proves the indispensability of the three compatibility in treating hemorrhoidal bleeding and promoting wound healing.

[0117] 3. Enhanced transdermal penetration and analgesia

[0118] 1. Borneol as a drug has the effects of refreshing the mind, clearing away heat and relieving pain, and can promote drug transdermal absorption. In Example 1, the combination of borneol and other drugs not only enhances the analgesic effect and significantly reduces the pain symptom score, but also improves the transdermal absorption of drugs, allowing other drugs to better reach the lesion site to play a role.

[0119] Compared with the case where borneol is lacking (Example 7), the analgesic effect is weakened and the therapeutic effect is affected, which reflects the important position of borneol in the formula. It works in synergy with other drugs to improve the overall therapeutic effect.

[0120] II. Invention of Preparation Process (I) Effect of Extraction Process Optimization on Efficacy

[0121] 1. Advantages of the extraction process in Example 1

[0122] 1. The water extraction and alcohol precipitation process adopted in embodiment 1 is first heated and decocted 2 times after soaking in water of 9 times of the total weight of the medicinal material for 1.5 hours, each time for 1.5 hours, and then alcohol precipitation is carried out. This process can fully extract the water-soluble effective ingredients in the medicinal materials such as Sophora flavescens, Radix Angelicae Dahuricae, Radix Sanguisorbae, such as the alkaloids in Sophora flavescens, the tannins in Radix Sanguisorbae, etc., and remove impurities by alcohol precipitation simultaneously, improve the purity of the extract. In clinical applications, the Kuzhi Xiaozhi ointment prepared by this process has a high effective ingredient content, and the therapeutic effect is remarkable, such as obvious improvement of symptoms, high hemorrhoid reduction rate, fast wound healing, etc. This shows that the extraction process can retain the effective ingredient of the medicine to greatest extent, and provides guarantee for the good effect of the medicine.

[0123] 2. Comparison of Changing the Number of Extractions (Example 8)

[0124] 1. Example 8 changes the extraction times to 1 time. Although the total effective rate is still 70%, there are gaps in the degree of symptom improvement, hemorrhoid reduction rate and wound healing time compared with Example 1. For example, the average score of 0.8±0.3 points (Example 8) after the treatment of blood in stool symptoms is higher than 0.3±0.2 points of Example 1, the average hemorrhoid reduction rate is about 45% (Example 8) which is lower than more than 50% of Example 1, and the average wound healing time is (7.2±1.8) days (Example 8) which is longer than (7±2) days of Example 1. This shows that the multiple extraction steps in the original extraction process are crucial for fully extracting the effective ingredients. Reducing the number of extractions will lead to incomplete extraction of the effective ingredients, thereby affecting the therapeutic effect of the drug, which reflects the rationality and superiority of the extraction process of Example 1.

[0125] (II) Importance of key parameters in formulation molding process

[0126] 1. The influence of temperature and time on the quality of paste

[0127] 1. In the preparation molding process of Example 1, the mixture is added to the melted vaseline and stirred evenly, and then heated to 75°C and maintained for 15 minutes. The control of this temperature and time can make the paste fully integrated, ensuring that the paste is delicate, uniform, easy to apply and absorb. The appropriate paste quality is conducive to the adhesion and penetration of the drug in the lesion site, prolonging the drug action time and improving bioavailability. If the temperature is too high or the time is too long, the drug ingredients may be destroyed or the paste may be too thin; if the temperature is too low or the time is too short, the paste may be uneven, affecting the release and absorption of the drug, and thus affecting the therapeutic effect.

[0128] 2. The role of vaseline matrix

[0129] 1. Vaseline as a matrix not only plays the role of an excipient, making the ointment easy to apply and adhere to the lesion site, but also has the effect of moisturizing and protecting the skin, preventing the ointment from irritating the skin around the anus. In Example 1, vaseline and drug extracts are evenly mixed to form a stable ointment system. Compared with the situation of not using vaseline or using other inappropriate matrices, the vaseline matrix helps to maintain the stability of the ointment, ensures the quality of the drug during storage and use, and is conducive to the release and penetration of the drug, thereby improving the therapeutic effect.

[0130] It provides a good carrier for drugs, enabling them to act continuously and effectively on the hemorrhoidal lesions.

[0131] In summary, Kuzhi Xiaozhi Ointment has significant advantages in treating hemorrhoids through carefully designed drug compatibility and scientifically optimized preparation process. The comparative study of Examples 1-8 fully proves the scientificity and effectiveness of its invention, and provides a more effective drug option for the treatment of hemorrhoids.

Claims

1. A Kuzhi Xiaozhi ointment is mainly made of the following raw materials in parts by weight: 30-50 parts of Sophora flavescens, 20-30 parts of Angelica dahurica, 20-30 parts of Sanguisorba officinalis, 15-25 parts of Platycladus orientalis leaves, 15-25 parts of Galla chinensis, and 5-10 parts of Borneol.

2. Kuzhi Xiaozhi ointment as claimed in claim 1, wherein the Sophora flavescens is the main drug.

3. Kuzhi Xiaozhi ointment as claimed in claim 1, wherein the Radix Angelicae Dahuricae and Radix Sanguisorbae are ministerial drugs.

4. Kuzhi Xiaozhi ointment as claimed in claim 1, wherein the Platycladus orientalis leaf and Galla chinensis are adjuvants.

5. The Kuzhi Xiaozhi ointment as claimed in claim 1, wherein the borneol is an adjuvant.

6. The preparation method of Kuzhi Xiaozhi ointment as claimed in claim 1, comprising the following steps: Raw material pretreatment: identify and inspect each medicinal material, remove impurities from Sophora flavescens, wash, soak, slice, and dry; remove impurities from Angelica dahurica, wash, soak, slice, and dry; remove impurities from Sanguisorba officinalis, wash, soak, slice, and dry; remove hard stems and impurities from Platycladus orientalis leaves, and dry in the shade or in the sun; crack open Galla chinensis and remove impurities; grind borneol into fine powder for later use; Extraction process: take Sophora flavescens, Angelica dahurica, Sanguisorba officinalis, Platycladus orientalis leaves, and Galla chinensis, add 8-10 times the total weight of the medicinal materials in water, soak for 1-2 hours, then heat and decoct for 2-3 times, each time for 1-2 hours, combine the decoctions, filter, obtain a filtrate, decompress the filtrate to a clear paste with a relative density of 1.05-1.10, then add ethanol to make the alcohol content reach 60%-70%, stand for 24-48 hours, take the supernatant, recover the ethanol and concentrate to an extract with a relative density of 1.20-1.25; Preparation molding process: add borneol powder to the above extract, stir evenly to obtain a mixture, heat and melt vaseline, slowly add the mixture to the molten vaseline, stir evenly, continue to heat to 70-80°C, keep for 10-20 minutes to allow the paste to fully blend, then pour into a sterile container while hot, cool to room temperature, and obtain Kuzhi Xiaozhi Ointment.