Hemorrhoids ointment and preparation method thereof
By using specific ingredients and preparation methods in hemorrhoid ointment, the problem of poor effect of existing hemorrhoid ointment is solved, and the effects of stopping bleeding, pain, anti-itching and healing rate are significantly improved.
Patent Information
- Application Number
- CN202510246349.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-03-04
- Publication Date
- 2025-05-23
AI Technical Summary
The existing hemorrhoid cream has poor effect on stopping bleeding, relieving itching and pain in the short term, and has a low cure rate.
A hemorrhoid ointment is used, which includes vaseline, nifedipine, hydrocortisone, lidocaine, witch hazel extract, aloe vera extract, panax notoginseng extract, lanolin, raw silk extract, glycerin and special solvents, and the transdermal absorption effect and stability of the drug are improved through specific preparation methods.
It significantly improves the ability of hemorrhoid ointment to analgesic, anti-inflammatory and anti-itchi, soothes and sedation, antioxidant, antibacterial, promotes blood circulation and accelerates repair, and improves the therapeutic effect of hemorrhoids.
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Abstract
Description
Technical Field
[0001] The invention relates to the technical field of local external medicines, in particular to a hemorrhoid ointment and a preparation method thereof. Background Art
[0002] Hemorrhoids, commonly known as hemorrhoids, are common anorectal diseases caused by congestion or congestion and swelling of the venous plexus in the anal canal or lower rectum. Hemorrhoids can be divided into external hemorrhoids, internal hemorrhoids and mixed hemorrhoids. The causes of the disease include downward displacement of anal cushions or varicose veins, as well as bad bowel habits, chronic diseases, low-fiber diet habits, etc. Common symptoms include bleeding during defecation, perianal itching, pain and prolapse of hemorrhoids. Early hemorrhoids may be asymptomatic, and different symptoms may occur depending on the type and severity of the disease, including bleeding, perianal itching, pain and prolapse. Its complications often include perianal skin irritation, itching, discomfort, perianal fullness and mild fecal incontinence.
[0003] Methods for treating hemorrhoids include changing lifestyle and eating habits, drug therapy, injection sclerotherapy, rubber band ligation therapy, infrared coagulation therapy, ultrasound-guided hemorrhoidal artery ligation, etc. Among them, the most commonly used treatment method is the use of topical medications for drug therapy. With the continuous deepening of research on the pathogenesis of hemorrhoids, as well as the development and application of new drugs, topical medication for hemorrhoids has also made certain progress. Mainly including, anti-inflammatory and analgesic drugs, such as ribavirin gel, lidocaine hydrochloride gel, etc., can relieve the pain and discomfort of hemorrhoid patients; healing-promoting drugs, such as cod liver oil ointment, vitamin E cream, etc., can promote the healing and repair of hemorrhoidal tissue; astringent hemostatic drugs, such as phenammycin suppositories, compound danshen pills, etc., can constrict blood vessels and reduce bleeding; antibacterial and anti-inflammatory drugs, such as chloramphenicol ointment, metronidazole suppositories, etc., can prevent infection and reduce inflammatory reactions.
[0004] In summary, there are many types of topical drugs for the treatment of hemorrhoids, but the effects are single. There are also problems such as inconvenience in use and poor hemostatic, antipruritic and analgesic effects and low cure rates in the short term caused by low solubility of active ingredients, poor transdermal absorption of drugs and poor drug stability.
[0005] Therefore, according to the related technology mentioned above, it is urgent to develop a hemorrhoid ointment and a preparation method thereof. Summary of the invention
[0006] In view of this, the purpose of the present invention is to provide a hemorrhoid ointment and a preparation method thereof, so as to solve the problems that the existing hemorrhoid ointment has poor hemostasis, itching and analgesia effects in a short period of time and has a low cure rate.
[0007] Based on the above purpose, the present invention provides a hemorrhoid ointment and a preparation method thereof.
[0008] A hemorrhoid ointment, comprising the following raw materials in parts by weight: 89-98 parts of vaseline, 0.1-0.9 parts of nifedipine, 0.5-2 parts of hydrocortisone, 2-6 parts of lidocaine, 1-2 parts of witch hazel extract, 1-5 parts of aloe extract, 1-3 parts of Panax notoginseng extract, 5-8 parts of lanolin, 1-5 parts of raw silk extract, 2-5 parts of glycerin, 0.3-0.5 parts of rutin from Sophora japonica seed, and 6-10 parts of solvent;
[0009] The raw silk extract is prepared from raw silk;
[0010] The solvent is prepared from menthol and capric acid.
[0011] Preferably, the preparation method of the raw silk extract is as follows:
[0012] Step A1: placing raw silk in a sodium carbonate aqueous solution at 98-100° C. for 50-60 minutes, then rinsing with deionized water, and then placing it in a sodium carbonate aqueous solution at 98-100° C. for 30-45 minutes, rinsing with deionized water again, and drying at 55-60° C. to obtain degummed silk;
[0013] Step A2: dissolve the degummed silk in a lithium bromide solution at 58-62° C. and stir for 60-70 min. After cooling, put it into a dialysis bag, dialyze it with deionized water for 3-6 days, filter it with absorbent cotton, and then centrifuge it at 10000-11000 rpm for 6-10 min. After freeze-drying, obtain the raw silk extract.
[0014] Preferably, the ratio of raw silk to sodium carbonate aqueous solution in step A1 is 20-100 g: 2-5 L;
[0015] The concentration of the sodium carbonate aqueous solution in step A1 is 0.0045-0.005 mol / L.
[0016] Preferably, the ratio of the degummed silk to the lithium bromide solution in step A2 is 5-15 g: 60-140 mL;
[0017] The concentration of the lithium bromide solution in step A2 is 9-9.3 mol / L;
[0018] The molecular weight cut-off of the dialysis bag in step A2 is 9000-12000Da.
[0019] Preferably, the preparation method of the solvent is as follows:
[0020] Adding capric acid to menthol, stirring at 80-85° C. and 300-350 rpm for 1-2 hours, and then stirring at 20-25° C. for 2-3 hours to obtain a solvent;
[0021] The molar ratio of menthol to capric acid is 0.8-1:2.
[0022] A method for preparing a hemorrhoid ointment comprises the following steps:
[0023] Step B1: dissolving Tween-20 in deionized water to obtain a Tween solution;
[0024] Step B2: Add lidocaine to a solvent at 20-25° C. and stir for 15-20 hours, then add it to a Tween solution under ultrasound assistance, then add witch hazel extract, aloe extract, and Panax notoginseng extract, and stir evenly to obtain a mixed liquid;
[0025] Step B3: After adding lanolin to vaseline, heat to 65-80°C, stir evenly, then cool to 25-40°C at room temperature, then add raw silk extract, mixed medicinal solution, hydrocortisone, glycerin and rutin in sequence while stirring, mix evenly to obtain a hemorrhoid ointment.
[0026] Preferably, the mass ratio of Tween-20 to deionized water in step B1 is 0.1-0.15:5.
[0027] Preferably, the usage ratio of the solvent, lidocaine, Tween solution, nifedipine witch hazel extract, aloe extract and Panax notoginseng extract in step B2 is 6-10:2-6:5.1-5.15:0.1-0.9:1-2:1-5:1-3.
[0028] Preferably, the power of the ultrasound assistance in step B2 is 150-200W; the ultrasound mode during the ultrasound assistance is a 1s pulse on / off mode.
[0029] Preferably, the mass ratio of vaseline, lanolin, raw silk extract, mixed liquid medicine, hydrocortisone, glycerin and rutin from Sophora japonica seed in step B3 is 89-98: 5-8: 1-5: 16.2-32.05: 0.5-2: 2-5: 0.3-0.5.
[0030] Beneficial effects of the present invention:
[0031] The invention provides a hemorrhoid ointment and a preparation method thereof. The invention processes raw silk to prepare a raw silk extract which can produce a synergistic effect with vaseline, lanolin and glycerin, thereby improving the hemorrhoid ointment's ability to moisturize, repair skin barriers and promote wound healing.
[0032] The solvent prepared by mixing menthol and capric acid in a specific ratio can not only improve the solubility of effective ingredients such as lidocaine, but also provide a stable carrier system for drugs. The solvent is combined with natural extracts such as rutin and sophora japonica added by the present invention to effectively improve the transdermal absorption effect and stability of the hemorrhoid ointment of the present invention, thereby further improving the analgesic, anti-inflammatory and antipruritic, soothing and sedative, anti-oxidant, antibacterial, blood circulation promotion and repair acceleration capabilities of the hemorrhoid ointment.
[0033] In the process of preparing the mixed liquid medicine, the present invention adds the solvent into the Tween solution under the assistance of ultrasound in a specific mode, which, on the one hand, improves the dispersibility of the mixed liquid medicine, so that the droplet size of part of the mixed liquid medicine reaches the nanometer level, thereby further improving the transdermal absorption effect of the hemorrhoid ointment of the present invention; on the other hand, the Tween-20 in the Tween solvent can also cooperate with ingredients such as rutin and sophora japonica to further improve the texture uniformity and stability of the ointment.
[0034] Therefore, compared with the prior art, the hemorrhoid ointment prepared by the present invention has better treatment ability for internal hemorrhoids, external hemorrhoids, mixed hemorrhoids and related complications, as well as broader application prospects. DETAILED DESCRIPTION
[0035] In order to make the objectives, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with specific embodiments.
[0036] The sources and properties of some of the raw materials used in the present invention are as follows:
[0037] Menthol was purchased from Shaanxi Shangping Pharmaceutical Excipients Co., Ltd., CAS: 89-78-1; witch hazel extract was purchased from Chengdu Pusi Biotechnology Co., Ltd.; aloe vera extract was purchased from Chengdu Pusi Biotechnology Co., Ltd.; Panax notoginseng extract was purchased from Chengdu Pusi Biotechnology Co., Ltd.; and rutin from Sophora japonica was purchased from Shaanxi Snot Biotechnology Co., Ltd., CAS: 7085-55-4.
[0038] Embodiment 1: A hemorrhoid ointment and a preparation method thereof, comprising the following steps:
[0039] S1: 20 g of raw silk was placed in a 2 L sodium carbonate aqueous solution with a concentration of 0.0045 mol / L at 98°C for 50 min, then rinsed with deionized water, and then placed in a 2 L sodium carbonate aqueous solution with a concentration of 0.0045 mol / L at 98°C for 30 min, rinsed with deionized water again, and dried at 55°C to obtain degummed silk;
[0040] S2: 5 g of degummed silk was dissolved in 60 mL of 9 mol / L lithium bromide solution at 58 °C and stirred for 60 min. After cooling, it was loaded into a dialysis bag with a molecular weight cutoff of 9000-12000 Da, dialyzed with deionized water for 3 days, filtered with absorbent cotton, and then centrifuged at 10000 rpm for 6 min. The supernatant was pre-frozen at -80 °C for 12 h, and finally freeze-dried at -50 °C and 10 Pa for 24 h to obtain raw silk extract;
[0041] S3: adding 2 mol of decanoic acid to 0.8 mol of menthol, stirring the mixture at 80°C and 300 rpm for 1 h, and then stirring the mixture at 20°C for 2 h to obtain a solvent;
[0042] S4: Dissolve 0.1 g of Tween-20 in 5 mL of deionized water to obtain a Tween solution;
[0043] S5: Add 2 g of lidocaine to 6 g of solvent at 20°C and stir for 15 h, then add it to 5.1 g of Tween solution under the assistance of ultrasound with a power of 150 W and an ultrasound mode of 1 s pulse on / off mode, then add 0.1 g of nifedipine, 1 g of witch hazel extract, 1 g of aloe extract, and 1 g of Panax notoginseng extract, and stir evenly to obtain a mixed liquid;
[0044] S6: Add 5 g of lanolin to 89 g of vaseline and heat to 65°C, stir evenly, then cool to 25°C at room temperature, then add 1 g of raw silk extract, 16.2 g of mixed medicinal solution, 0.5 g of hydrocortisone, 2 g of glycerin and 0.3 g of rutin from Sophora japonica seeds in sequence while stirring, mix evenly to obtain a hemorrhoid ointment.
[0045] Embodiment 2: A hemorrhoid ointment and a preparation method thereof, comprising the following steps:
[0046] S1: 40 g of raw silk was placed in a 3 L sodium carbonate aqueous solution with a concentration of 0.0047 mol / L at 99° C. for 53 min, then rinsed with deionized water, and then placed in a 3 L sodium carbonate aqueous solution with a concentration of 0.0047 mol / L at 99° C. for 35 min, rinsed with deionized water again, and dried at 57° C. to obtain degummed silk;
[0047] S2: 8 g of degummed silk was dissolved in 90 mL of lithium bromide solution at 59 ° C and the concentration was 9.1 mol / L and stirred for 63 min. After cooling, it was loaded into a dialysis bag with a molecular weight cutoff of 9000-12000 Da, dialyzed with deionized water for 4 days, filtered with absorbent cotton, and then centrifuged at 10300 rpm for 7 min. The supernatant was pre-frozen at -80 ° C for 13 h, and finally freeze-dried at -50 ° C and 10 Pa for 25 h to obtain raw silk extract;
[0048] S3: adding 2 mol of capric acid to 0.9 mol of menthol, stirring the mixture at 82°C and 320 rpm for 1.2 h, and then stirring the mixture at 22°C for 2.3 h to obtain a solvent;
[0049] S4: Dissolve 0.12 g of Tween-20 in 5 mL of deionized water to obtain a Tween solution;
[0050] S5: Add 3 g of lidocaine to 7 g of solvent at 22°C and stir for 17 h, then add to 5.12 g of Tween solution under the assistance of ultrasound with a power of 170 W and an ultrasound mode of 1 s pulse on / off mode, then add 0.3 g of nifedipine, 1.3 g of witch hazel extract, 2 g of aloe extract, and 2 g of Panax notoginseng extract, and stir evenly to obtain a mixed liquid;
[0051] S6: Add 6 g of lanolin to 92 g of vaseline and heat to 70°C, stir evenly, then cool to 30°C at room temperature, then add 2 g of raw silk extract, 17.75 g of mixed medicinal solution, 1 g of hydrocortisone, 3 g of glycerin and 0.35 g of rutin from Sophora japonica seeds in sequence while stirring, mix evenly to obtain a hemorrhoid ointment.
[0052] Embodiment 3: A hemorrhoid ointment and a preparation method thereof, comprising the following steps:
[0053] S1: 70 g of raw silk was placed in a 4 L sodium carbonate aqueous solution with a concentration of 0.0048 mol / L at 100° C. for 57 min, then rinsed with deionized water, and then placed in a 4 L sodium carbonate aqueous solution with a concentration of 0.0048 mol / L at 100° C. for 40 min, rinsed with deionized water again, and dried at 58° C. to obtain degummed silk;
[0054] S2: 12 g of degummed silk was dissolved in 110 mL of lithium bromide solution at a concentration of 9.2 mol / L at 61°C and stirred for 67 min. After cooling, it was loaded into a dialysis bag with a molecular weight cutoff of 9000-12000 Da, dialyzed with deionized water for 5 days, filtered with absorbent cotton, and then centrifuged at 10700 rpm for 8 min. The supernatant was pre-frozen at -80°C for 14 h, and finally freeze-dried at -50°C and 10 Pa for 26 h to obtain a raw silk extract;
[0055] S3: 2 mol of decanoic acid was added to 1 mol of menthol, followed by stirring at 84°C at 340 rpm for 1.7 h, and then stirring at 23°C for 2.7 h to obtain a solvent;
[0056] S4: Dissolve 0.14 g of Tween-20 in 5 mL of deionized water to obtain a Tween solution;
[0057] S5: Add 5 g of lidocaine to 9 g of solvent at 24°C and stir for 18 h, then add to 5.14 g of Tween solution under the assistance of ultrasound with a power of 180 W and an ultrasound mode of 1 s pulse on / off mode, then add 0.6 g of nifedipine, 1.7 g of witch hazel extract, 4 g of aloe extract, and 2 g of Panax notoginseng extract, and stir evenly to obtain a mixed liquid;
[0058] S6: Add 7 g of lanolin to 95 g of vaseline and heat to 75°C, stir evenly, then cool to 35°C at room temperature, then add 4 g of raw silk extract, 27.44 g of mixed medicinal solution, 1.5 g of hydrocortisone, 4 g of glycerin and 0.4 g of rutin from Sophora japonica seeds in sequence while stirring, mix evenly to obtain a hemorrhoid ointment.
[0059] Embodiment 4: A hemorrhoid ointment and a preparation method thereof, comprising the following steps:
[0060] S1: 100 g of raw silk was placed in a 5 L sodium carbonate aqueous solution with a concentration of 0.005 mol / L at 100° C. for 60 min, then rinsed with deionized water, and then placed in a 5 L sodium carbonate aqueous solution with a concentration of 0.005 mol / L at 100° C. for 45 min, rinsed with deionized water again, and dried at 60° C. to obtain degummed silk;
[0061] S2: 15 g of degummed silk was dissolved in 140 mL of lithium bromide solution at a concentration of 9.3 mol / L at 62 °C and stirred for 70 min. After cooling, it was loaded into a dialysis bag with a molecular weight cutoff of 9000-12000 Da, dialyzed with deionized water for 6 days, filtered with absorbent cotton, and then centrifuged at 11000 rpm for 10 min. The supernatant was pre-frozen at -80 °C for 15 h, and finally freeze-dried at -50 °C and 10 Pa for 27 h to obtain a raw silk extract;
[0062] S3: adding 2 mol of decanoic acid to 1 mol of menthol, stirring the mixture at 85°C and 350 rpm for 2 h, and then stirring the mixture at 25°C for 3 h to obtain a solvent;
[0063] S4: Dissolve 0.15 g of Tween-20 in 5 mL of deionized water to obtain a Tween solution;
[0064] S5: Add 6 g of lidocaine to 10 g of solvent at 25°C and stir for 20 h, then add to 5.15 g of Tween solution under the assistance of ultrasound with a power of 200 W and an ultrasound mode of 1 s pulse on / off mode, then add 0.9 g of nifedipine, 2 g of witch hazel extract, 5 g of aloe extract, and 3 g of Panax notoginseng extract, and stir evenly to obtain a mixed liquid;
[0065] S6: Add 8 g of lanolin to 98 g of vaseline and heat to 80°C, stir evenly, then cool to 40°C at room temperature, then add 5 g of raw silk extract, 32.05 g of mixed medicinal solution, 2 g of hydrocortisone, 5 g of glycerin and 0.5 g of rutin from Sophora japonica seeds in sequence while stirring, mix evenly to obtain a hemorrhoid ointment.
[0066] Comparative Example 1:
[0067] Compared with Example 1, this comparative example only replaces the step of "pre-freezing the supernatant at -80°C for 12h and finally freeze-drying at -50°C and 10Pa for 24h" with "drying the supernatant at 25°C for 45h" in the preparation process of the raw silk extract. The remaining steps and parameters are the same and will not be repeated in this comparative example. Finally, a hemorrhoid ointment is obtained;
[0068] Comparative Example 2:
[0069] Compared with Example 1, this comparative example only replaces "adding 2 mol of capric acid to 0.8 mol of menthol" in the preparation process of the solvent with "adding 2.5 mol of capric acid to 0.3 mol of menthol", and the remaining steps and parameters are the same, which will not be repeated in this comparative example, and finally a hemorrhoid ointment is obtained;
[0070] Comparative Example 3:
[0071] Compared with Example 1, in this comparative example, only the "then added to 5.1 g of Tween solution under the assistance of ultrasound with a power of 150 W and an ultrasonic mode of 1 s pulse on / off mode" in the preparation process of the mixed liquid is replaced by "then added to 5.1 g of Tween solution while stirring", and the other steps and parameters are the same, which will not be repeated in this comparative example, and finally a hemorrhoid ointment is obtained;
[0072] Comparative Example 4:
[0073] Compared with Example 1, in this comparative example, only the following in the preparation process of the mixed liquid medicine: "adding 2g of lidocaine to 6g of solvent at 20°C and stirring for 15h, then adding it to 5.1g of Tween solution under the assistance of ultrasound with a power of 150W and an ultrasonic mode of 1s pulse on / off mode, then adding 1g of witch hazel extract, 1g of aloe extract, and 1g of Panax notoginseng extract, and stirring to obtain a mixed liquid medicine" is replaced with "adding 2g of lidocaine to 2g of menthol at 20°C and stirring for 15h, then adding 1g of witch hazel extract, 1g of aloe extract, and 1g of Panax notoginseng extract, and stirring to obtain a mixed liquid medicine", and the remaining steps and parameters are the same, which will not be repeated in this comparative example, and finally a hemorrhoid ointment is obtained;
[0074] Comparative Example 5:
[0075] Compared with Example 1, in this comparative example, 1 g of raw silk extract was not added during the preparation of the hemorrhoid ointment, and the remaining steps and parameters were the same, which will not be repeated in this comparative example, and finally the hemorrhoid ointment was obtained;
[0076] Comparative Example 6:
[0077] Compared with Example 1, 0.3 g of rutin from the root of sophora japonica was not added during the preparation of the hemorrhoid ointment in this comparative example, and the remaining steps and parameters were the same, which will not be repeated in this comparative example, and finally the hemorrhoid ointment was obtained.
[0078] Performance Test:
[0079] 1. Animal Testing
[0080] Determination of anti-inflammatory ability:
[0081] Take Kunming mice, half male and half female, and randomly divide them into 10 groups, 50 in each group. Take 0.05mL of xylene and evenly apply it to the front and back sides of the left ear of all mice to cause inflammation. After 0.5h, 1g of hemorrhoid ointment prepared by Example 1-Example 4 and Comparative Example 1-Comparative Example 6 is evenly applied to the inflamed auricle of each group of mice (such as: 1g of hemorrhoid ointment prepared by Example 1 is evenly applied to the inflamed auricle of the first group of mice, and 1g of hemorrhoid ointment prepared by Example 2 is evenly applied to the inflamed auricle of the second group of mice). After 4h, the mice were killed by cervical dislocation, and the two ears were cut off along the auricle baseline. An ear piece was punched in the same position with a diameter of 8mm puncher, and weighed on an analytical balance. The average value of the difference between the weights of the two ear pieces of each group of mice was obtained to reflect the anti-inflammatory ability of each group of hemorrhoid ointment and normal saline. The measurement results are shown in Table 1.
[0082] Determination of acute toxicity:
[0083] 24 hours before administration, shave the hair on both sides of the spine of the rabbit back, and the hair removal area is about 15cm×10cm. Preparation of damaged skin: shave the hair in the same way as the intact skin, disinfect it 24 hours after shaving, scratch the skin with a needle, do not hurt the dermis, and slightly bleed. The rabbits were divided into 2 groups on average, one of which was a blank group and the other was an experimental group. The experimental group contained an intact skin group and a damaged skin group, each group had 6 rabbits, half male and half female. Apply the hemorrhoid ointment evenly to the depilated area on the back of the animal. After 24 hours, wash off the tested ointment and observe continuously for 7 days; then observe and analyze whether the rabbits have poisoning reactions. According to this method, the acute toxicity of the hemorrhoid ointment prepared by Example 1-Example 4 and Comparative Example 1-Comparative Example 6 was determined, and the results are shown in Table 1.
[0084] Determination of irritation:
[0085] The preparation of intact skin and damaged skin is the same as the method in acute toxicity determination. 2g of hemorrhoid cream is applied to the left depilatory area of intact and damaged skin rabbit back, and the right depilatory area is coated with a blank matrix ointment of the same area, 3 in each group, administered once every 24 hours, for 7 consecutive days. Remove the paste remaining on the back of the rabbit, and observe whether erythema and edema appear in the local medication site after drug withdrawal. According to this method, the hemorrhoid ointment prepared by Example 1-Example 4 and Comparative Example 1-Comparative Example 6 is subjected to irritation determination, and the determination results are shown in Table 1.
[0086] Determination of mucosal irritation:
[0087] Take Kunming mice, half male and half female, 50 mice in each group, apply 0.5g of hemorrhoid ointment to the anus once a day, and keep it for 3 minutes, for a total of 10 times. Results: After 10 days of application, observe the anal mucosa of each mouse with the naked eye to record whether redness and swelling appear, and then perform a histopathological examination to analyze whether there are abnormal changes. According to this method, the hemorrhoid ointment prepared by Example 1-Example 4 and Comparative Example 1-Comparative Example 6 was tested for irritation, and the test results are shown in Table 1.
[0088] Table 1
[0089] project Anti-inflammatory ability / mg Acute toxicity Irritant Mucosal irritation Example 1 2.46 No toxic reaction No erythema, no edema No redness, swelling, or abnormality Example 2 2.39 No toxic reaction No erythema, no edema No redness, swelling, or abnormality Example 3 2.32 No toxic reaction No erythema, no edema No redness, swelling, or abnormality Example 4 2.25 No toxic reaction No erythema, no edema No redness, swelling, or abnormality Comparative Example 1 2.82 No toxic reaction No erythema, no edema No redness, swelling, or abnormality Comparative Example 2 2.97 No toxic reaction No erythema, no edema No redness, swelling, or abnormality Comparative Example 3 3.33 No toxic reaction No erythema, no edema No redness, swelling, or abnormality Comparative Example 4 5.73 No toxic reaction No erythema, no edema No redness, swelling, or abnormality Comparative Example 5 3.58 No toxic reaction No erythema, no edema No redness, swelling, or abnormality Comparative Example 6 3.16 No toxic reaction No erythema, no edema No redness, swelling, or abnormality
[0090] Data Analysis:
[0091] As can be seen from Table 1, the hemorrhoid ointment prepared by the present invention has good anti-inflammatory ability and does not have acute toxicity, skin irritation and anal mucosal irritation;
[0092] This may be because the ingredients used in the preparation process of the hemorrhoid ointment of the present invention are mostly natural plant extracts, and the dosage of each ingredient of the present invention is within the appropriate use range, so it has no acute toxicity, skin irritation and anal mucosal irritation. The hydrocortisone added by the invention is a glucocorticoid and can relieve inflammation and itching; the witch hazel extract also has an anti-inflammatory effect; lidocaine is a local anesthetic and can relieve pain and discomfort; vaseline, lanolin, glycerin and raw silk extract can moisturize, repair skin barriers and promote healing; aloe extract and menthol have sedative and cooling effects and are suitable for sensitive or damaged skin; Panax notoginseng extract and rutin from Sophora japonica have antioxidant effects and help reduce free radical damage; the witch hazel extract and capric acid have a certain antibacterial effect and can prevent infection; the Panax notoginseng extract helps to improve local blood circulation and accelerate repair; combined with the specific preparation method of the invention, the solubility of the effective ingredient with anti-inflammatory effect can be improved to the greatest extent, wherein the solvent prepared by neutralizing capric acid with menthol in a specific ratio can also be used as a dispersed phase of a nanoemulsion to provide a stable carrier system for the drug; the solvent is combined with the natural extracts such as rutin from Sophora japonica added by the invention to effectively improve the transdermal absorption effect and stability of the hemorrhoid ointment of the invention, thereby further improving the anti-inflammatory and accelerated repair capabilities of the hemorrhoid ointment.
[0093] 2. Clinical Trials
[0094] Analgesic effect:
[0095] A group of 200 people (male or female randomly) participated in the analgesic effect test, aged 20-65 years old, all of whom suffered from internal hemorrhoids, external hemorrhoids, mixed hemorrhoids and had anal distension and pain symptoms, and the 200 people were randomly divided into 10 groups, 20 people in each group, and the patients in each group were respectively used with the hemorrhoid ointment prepared by Example 1 to Example 4 of the present invention and Comparative Example 1 to Comparative Example 6 (such as: the first group of patients used the hemorrhoid ointment prepared by Example 1, and the second group of patients used the hemorrhoid ointment prepared by Example 2), and the percentage of pain patients achieving the analgesic effect in each group after 1 day of use was determined. The analgesic effect determination results of each group are shown in Table 2;
[0096] Hemostatic effect:
[0097] A group of 200 people (male or female randomly) participated in the hemostatic effect test, aged 20-65 years old, all of whom suffered from internal hemorrhoids, external hemorrhoids, mixed hemorrhoids and had anal bleeding symptoms. The 200 people were randomly divided into 10 groups, 20 people in each group, and the patients in each group were respectively used with the hemorrhoid ointment prepared by Example 1 to Example 4 of the present invention and Comparative Example 1 to Comparative Example 6 (such as: the first group of patients used the hemorrhoid ointment prepared by Example 1, and the second group of patients used the hemorrhoid ointment prepared by Example 2), and the percentage of patients in each group who achieved the hemostatic effect after 1 day of use was determined. The hemostatic effect determination results of each group are shown in Table 2;
[0098] Anti-itching effect:
[0099] A group of 200 people (male or female randomly) participated in the hemostatic effect test, aged 20-65 years old, all of whom suffered from internal hemorrhoids, external hemorrhoids, mixed hemorrhoids and had anal itching symptoms, and the 200 people were randomly divided into 10 groups, 20 people in each group, and the patients in each group were respectively used with the hemorrhoid ointment prepared by Example 1 to Example 4 of the present invention and Comparative Example 1 to Comparative Example 6 (such as: the first group of patients used the hemorrhoid ointment prepared by Example 1, and the second group of patients used the hemorrhoid ointment prepared by Example 2), and the percentage of patients in each group who achieved the antipruritic effect after 1 day of use was determined. The antipruritic effect determination results of each group are shown in Table 2;
[0100] Cure rate and recurrence rate test:
[0101] A group of 200 people (male or female randomly selected) participated in the recurrence rate test, aged 20-65 years old, all of whom suffered from internal hemorrhoids, external hemorrhoids, mixed hemorrhoids and had complications such as anal itching symptoms. The 200 people were randomly divided into 10 groups, 20 people in each group, and the patients in each group were respectively used the hemorrhoid ointment prepared by Examples 1 to 4 of the present invention and Comparative Examples 1 to Comparative Examples 6 and sealed and stored for 30 days (such as: the first group of patients used the hemorrhoid ointment prepared by Example 1, and the second group of patients used the hemorrhoid ointment prepared by Example 2). The percentage of patients who achieved a cure effect in each group after one course of treatment, then stopped taking the medicine, and counted the recurrence rate of the cured patients in each group after one year. The results of the cure rate and recurrence rate determination of each group are shown in Table 2;
[0102] Directions:
[0103] After washing the affected area with cold water, apply hemorrhoid ointment evenly to the affected area, 1-2 grams each time, twice a day (preferably once in the morning and once in the evening, with an interval of about 8 hours), one course of treatment is 10 days.
[0104] Table 2
[0105]
[0106]
[0107] Analysis of the clinical trial process and results shows that the hemorrhoid ointment prepared by the present invention has more excellent hemostatic, analgesic and antipruritic abilities, more stable therapeutic effects on internal hemorrhoids, external hemorrhoids, mixed hemorrhoids and complications, and the hemorrhoid ointment prepared by the present invention has a shorter treatment time and a simple method of use.
[0108] This may be because the raw silk extract prepared by freeze-drying by processing raw silk contains more active ingredients and can produce synergistic effects with vaseline, lanolin and glycerin, thereby improving the ability of the hemorrhoid ointment to moisturize, repair skin barrier and promote wound healing; the solvent prepared by mixing menthol and capric acid in a specific ratio can not only improve the solubility of effective ingredients such as lidocaine, but also provide a stable carrier system for drugs, and the natural extracts such as rutin and sophora japonica added by the present invention effectively improve the transdermal absorption effect and stability of the hemorrhoid ointment of the present invention, thereby further improving the analgesic, anti-inflammatory and itching, soothing and sedative, antioxidant, antibacterial, blood circulation promotion and repair acceleration of the hemorrhoid ointment; and in the process of preparing the mixed liquid, the solvent is added to the Tween solution under the assistance of ultrasound in a specific mode, on the one hand, the dispersibility of the mixed liquid is improved, so that the droplet size of some mixed liquid reaches the nanometer level, thereby further improving the transdermal absorption effect of the hemorrhoid ointment of the present invention; on the other hand, the Tween-20 in the Tween solvent can also cooperate with ingredients such as rutin and sophora japonica to further improve the texture uniformity and stability of the ointment.
[0109] Those skilled in the art should understand that the discussion of any of the above embodiments is merely illustrative and is not intended to imply that the scope of the present invention is limited to these examples. Under the concept of the present invention, the technical features in the above embodiments or different embodiments may be combined, the steps may be implemented in any order, and there are many other variations of the different aspects of the present invention as described above, which are not provided in detail for the sake of simplicity.
[0110] The present invention is intended to cover all such substitutions, modifications and variations that fall within the broad scope of the appended claims. Therefore, any omissions, modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.
Claims
1. A hemorrhoid ointment, characterized in that: The invention comprises the following raw materials in parts by weight: 89-98 parts of vaseline, 0.1-0.9 parts of nifedipine, 0.5-2 parts of hydrocortisone, 2-6 parts of lidocaine, 1-2 parts of witch hazel extract, 1-5 parts of aloe extract, 1-3 parts of notoginseng extract, 5-8 parts of lanolin, 1-5 parts of raw silk extract, 2-5 parts of glycerin, 0.3-0.5 parts of rutin from Sophora japonica seed, and 6-10 parts of solvent; The raw silk extract is prepared from raw silk; The solvent is prepared from menthol and capric acid.
2. The hemorrhoid ointment according to claim 1, characterized in that The preparation method of the raw silk extract is as follows: Step A1: placing raw silk in a sodium carbonate aqueous solution at 98-100° C. for 50-60 minutes, then rinsing with deionized water, and then placing it in a sodium carbonate aqueous solution at 98-100° C. for 30-45 minutes, rinsing with deionized water again, and drying at 55-60° C. to obtain degummed silk; Step A2: dissolve the degummed silk in a lithium bromide solution at 58-62° C. and stir for 60-70 min. After cooling, put it into a dialysis bag, dialyze it with deionized water for 3-6 days, filter it with absorbent cotton, and then centrifuge it at 10000-11000 rpm for 6-10 min. After freeze-drying, obtain the raw silk extract.
3. The hemorrhoid ointment according to claim 2, characterized in that In step A1, the ratio of raw silk to sodium carbonate aqueous solution is 20-100 g: 2-5 L; The concentration of the sodium carbonate aqueous solution in step A1 is 0.0045-0.005 mol / L.
4. The hemorrhoid ointment according to claim 2, characterized in that The degummed silk and lithium bromide solution in step A2 are used in a ratio of 5-15 g: 60-140 mL; The concentration of the lithium bromide solution in step A2 is 9-9.3 mol / L; The molecular weight cut-off of the dialysis bag in step A2 is 9000-12000Da.
5. The hemorrhoid ointment according to claim 1, characterized in that The preparation method of the solvent is as follows: Adding capric acid to menthol, stirring at 80-85° C. and 300-350 rpm for 1-2 hours, and then stirring at 20-25° C. for 2-3 hours to obtain a solvent; The molar ratio of menthol to capric acid is 0.8-1:
2.
6. A method for preparing a hemorrhoid ointment, characterized in that: The following steps are involved: Step B1: dissolving Tween-20 in deionized water to obtain a Tween solution; Step B2: Add lidocaine to a solvent at 20-25° C. and stir for 15-20 hours, then add it to a Tween solution under ultrasound assistance, then add nifedipine, witch hazel extract, aloe extract, and Panax notoginseng extract, and stir evenly to obtain a mixed liquid; Step B3: After adding lanolin to vaseline, heat to 65-80°C, stir evenly, then cool to 25-40°C at room temperature, then add raw silk extract, mixed medicinal solution, hydrocortisone, glycerin and rutin in sequence while stirring, mix evenly to obtain a hemorrhoid ointment.
7. The method for preparing the hemorrhoid ointment according to claim 6, characterized in that: The mass ratio of Tween-20 to deionized water in step B1 is 0.1-0.15:
5.
8. The method for preparing the hemorrhoid ointment according to claim 6, characterized in that: The usage ratio of the solvent, lidocaine, Tween solution, witch hazel extract, aloe extract and Panax notoginseng extract in step B2 is 6-10:2-6:5.1-5.15:0.1-0.9:1-2:1-5:1-3.
9. The method for preparing the hemorrhoid ointment according to claim 6, characterized in that: The power of the ultrasound assistance in step B2 is 150-200W; the ultrasound mode during the ultrasound assistance is a 1s pulse on / off mode.
10. The method for preparing the hemorrhoid ointment according to claim 6, characterized in that: The mass ratio of vaseline, lanolin, raw silk extract, mixed liquid, hydrocortisone, glycerin and rutin from Sophora japonica seed in step B3 is 89-98: 5-8: 1-5: 16.2-32.05: 0.5-2: 2-5: 0.3-0.5.