A Chinese medicine composition for treating hemorrhoids and preparation method thereof

Abstract

The invention discloses a Chinese medicine composition for treating hemorrhoids and a preparation method thereof, and relates to the technical field of medical gel; the Chinese medicine composition for treating hemorrhoids consists of carboxymethyl chitosan modified Chinese medicine liposomes, a synergistic gel base, tannic acid, propylene glycol, triethanolamine and sodium methylparaben; the carboxymethyl chitosan modified Chinese medicine liposomes consist of Chinese medicine extracts, carboxymethyl chitosan, soybean lecithin and cholesterol; the synergistic gel base consists of sodium alginate and sodium carboxymethyl cellulose; a liposome gel composite drug-carrying system is formed by crosslinking the carboxymethyl chitosan modified Chinese medicine liposomes with the synergistic gel base under tannic acid, which has a dual sustained-release effect, significantly enhances the encapsulation effect, helps to improve the stability of the active ingredients, prolongs the retention time of the drug at the treatment site, and effectively improves the therapeutic effect of hemorrhoids.

Description

Technical Field

[0001] The invention belongs to the technical field of medical gel, and specifically refers to a traditional Chinese medicine composition for treating hemorrhoids and a preparation method thereof. Background Art

[0002] Hemorrhoids are lumps formed by the expansion and congestion of the venous plexus in the tissues around the rectum and anus, which may be accompanied by pain and bleeding symptoms. The prevalence of hemorrhoids in the general population is as high as about 40%, and the highest incidence is among the middle-aged and elderly people. Hemorrhoid patients most often show recurrent chronic rectal bleeding and prolapsed hemorrhoids. In the case of thrombosis or fissures, hemorrhoid patients will experience extreme pain, causing great life difficulties and mental stress to the patients. Therefore, alleviating patients' pain and improving their quality of life are important directions for the treatment of hemorrhoids.

[0003] At present, Western medicine clinical treatment for hemorrhoids mainly includes conservative treatment and surgical treatment. Although surgical operation can eradicate the cause of the disease, it is traumatic to a certain extent, with a high risk of postoperative complications. In addition, surgery has various contraindications and cumbersome postoperative care. Most hemorrhoid patients find it difficult to accept this treatment, and most patients with mild symptoms will choose conservative treatment first. Potassium permanganate solution fumigation and sitz bath is a commonly used method for clinical treatment of hemorrhoids, which can control infection and improve patients' clinical symptoms, but the long-term effect is not ideal. Traditional Chinese medicine has rich experience in treating hemorrhoids. Chinese medicine gel preparations can directly apply the drug to the affected area, which is beneficial to the transdermal absorption of the drug, has a lubricating and anti-infection effect on the skin and mucous membranes, and has little irritation and few adverse reactions. It is suitable for all stages of hemorrhoids and postoperative recovery treatment.

[0004] The existing technology currently has the following problems:

[0005] Due to the complexity and diversity of Chinese medicine ingredients, Chinese medicine gel is easily oxidized and hydrolyzed, which is not conducive to the stability of the active ingredients and is not conducive to prolonging the retention time of the drug in the affected area, thus limiting the therapeutic effect. Summary of the invention

[0006] In view of the above situation, in order to overcome the defects of the prior art, the present invention proposes a traditional Chinese medicine composition for treating hemorrhoids, comprising the following components in parts by weight: 50-60 parts of carboxymethyl chitosan modified traditional Chinese medicine liposomes, 20-30 parts of synergistic gel base, 6-10 parts of tannic acid, 2-3 parts of propylene glycol, 1-2 parts of triethanolamine, and 0.5-1 part of sodium methylparaben.

[0007] The carboxymethyl chitosan modified traditional Chinese medicine liposome comprises the following components in parts by weight: 8-10 parts of traditional Chinese medicine extract, 40-50 parts of carboxymethyl chitosan, 18-20 parts of soybean lecithin, and 3-4 parts of cholesterol.

[0008] The synergistic gel base comprises the following components in parts by weight: 30-40 parts of sodium alginate and 10-20 parts of sodium carboxymethyl cellulose.

[0009] The raw materials of the Chinese medicine extract include the following components in parts by weight: 3-5 parts of cinnabar, 3-5 parts of realgar, 3-5 parts of red ochre, 3-5 parts of dragon's blood, 3-5 parts of myrrh, 3-5 parts of coptis chinensis, 3-5 parts of red powder, 3-5 parts of calomel, 3-5 parts of borneol, and 3-5 parts of lithospermum.

[0010] The method for preparing the carboxymethyl chitosan modified Chinese medicine liposome specifically comprises the following steps:

[0011] (1) Cinnabar, realgar, red ochre, dragon's blood, myrrh, Sichuan coptis root, red powder, light powder, borneol, and lithospermum officinale are crushed, passed through a 60-80 mesh sieve, mixed evenly, added with 3-5 times the amount of distilled water and boiled for 2-3 times, filtered while hot, combined the filtrate, and then concentrated to 1 / 5 to 1 / 3 of the original volume of the filtrate, dried, crushed, and selected Chinese medicinal materials that promote blood circulation and remove blood stasis, reduce swelling and relieve pain, clear away heat and detoxify, and preserve and promote tissue regeneration. The Chinese medicinal materials are combined and used to effectively treat hemorrhoids and relieve discomfort symptoms such as bleeding and pain, thereby obtaining a Chinese medicinal extract;

[0012] (2) 80-100 mg of the Chinese herbal extract described in step S1, 180-200 mg of soybean lecithin, and 30-40 mg of cholesterol are added to 20-30 mL of an ethanol solution with a mass fraction of 80%, stirred at a constant temperature, slowly injected into the aqueous phase, hydrated at a constant temperature, evaporated clean ethanol, ultrasonically crushed, and filtered through a 0.22 μm water membrane. The active ingredients of Chinese herbal medicine such as alkaloids, flavonoids, and polysaccharides not only have significant pharmacological effects, but also form a drug-excipient delivery carrier by co-assembling with traditional liposomes, thereby exerting a stronger efficacy and reducing the occurrence of adverse reactions, thereby obtaining Chinese herbal medicine liposomes;

[0013] (3) Add chitosan to 20 mL of isopropanol solution and react for 3-4 hours, then add 25 mL of 30% sodium hydroxide solution and set aside, weigh 3.0 g of chloroacetic acid and dissolve it in 20 mL of isopropanol solution, slowly pour it into the chitosan solution under stirring conditions using a magnetic stirrer, fully react for 1-2 hours, let stand for stratification, remove the upper layer solution, take 50 mL of distilled water and add it, magnetically stir for 5 minutes, adjust the pH to 7.0 with 10% hydrochloric acid solution, centrifuge once, fully precipitate the supernatant with methanol, centrifuge twice, then add anhydrous ethanol to wash the precipitate, and centrifuge three times. By modifying chitosan, the water solubility is improved and the characteristics of amphoteric polyelectrolyte are given, so that the modified chitosan has good biocompatibility and biodegradability, and a carboxymethyl chitosan solution is obtained;

[0014] (4) slowly adding the Chinese medicine liposomes described in step (2) into the carboxymethyl chitosan solution described in step (3), placing the mixed solution in a magnetic stirrer, controlling the temperature at 40-50°C, the rotation speed at 10-20 rpm, stirring for 0.5-1 h, and then subjecting the mixture to intermittent ultrasonic treatment for 10-20 min, modifying the Chinese medicine liposomes with carboxymethyl chitosan to form a coated liposome that can prevent drug leakage, improve the stability of the drug and liposomes, prolong the sustained release time of the embedded substance, and effectively prolong the retention time of the drug, thereby obtaining carboxymethyl chitosan-modified Chinese medicine liposomes;

[0015] Preferably, in step (3), the amount of chitosan added is 0.5-0.6 g, which can ensure sufficient reaction with chloroacetic acid, thereby effectively introducing carboxymethyl groups;

[0016] Preferably, in step (4), during the intermittent ultrasonic treatment, the process is operated for 2 minutes and stopped for 2 minutes. By intermittently applying ultrasound, the coating film can be prevented from being destroyed under continuous action, which is beneficial to the integrity and protection of the coating film.

[0017] The present invention also provides a method for preparing a Chinese medicine composition for treating hemorrhoids, which specifically comprises the following steps:

[0018] S1. Dissolve sodium alginate in 80 mL of water, add sodium carboxymethyl cellulose, stir, and homogenize under high pressure at a homogenization pressure of 600-800 bar and a homogenization time of 1-3 min. High-pressure homogenization is beneficial to the uniformity of the distribution of sodium alginate and sodium carboxymethyl cellulose, and also helps to achieve a better cross-linking effect in the subsequent step. Then, heat in a water bath at 30-40° C., stir at a speed of 400-500 rpm, and stir for 20-30 min to cross-link the sodium alginate and sodium carboxymethyl cellulose molecules to form a gel network structure, which has the functions of film-forming and absorbing water. When applied to the affected area of ​​hemorrhoids, it can provide a moist environment to prevent bacterial growth, and can also exert the anti-inflammatory, hemostatic, and healing effects of the gel components to promote the healing of ruptured wounds, thereby obtaining a synergistic gel base.

[0019] S2, adding carboxymethyl chitosan modified Chinese medicine liposomes to the synergistic gel base described in step S1, stirring evenly, then adding tannic acid, stirring for 15-25min, adjusting the pH to 5.0-6.0, heating in a water bath, controlling the temperature to 40-50°C, and heating time to 1-2h, by distributing the carboxymethyl chitosan modified Chinese medicine liposomes in the synergistic gel base structure, reducing the fluidity of the liposomes, protecting the integrity and stability of the active ingredients, and effectively preventing the drug from seeping out and leaking, at the same time, the presence of the liposomes can prevent the sudden release effect of the hydrogel, and also give the composite system a dual sustained-release effect, thereby prolonging the retention time of the drug, improving the therapeutic effect on hemorrhoids, and obtaining a liposome gel composite drug-carrying system;

[0020] S3, adding propylene glycol to the liposome gel composite drug delivery system described in step S2, magnetic stirring for 10 minutes, then adding triethanolamine and sodium methylparaben, stirring evenly, to form a composite gel, wherein propylene glycol helps other components to be dispersed into the liposome gel composite drug delivery system, triethanolamine helps to improve the gel performance, and sodium methylparaben enhances the antibacterial property, reduces the bacterial infection of the hemorrhoid diseased part, and obtains a Chinese medicine composition for treating hemorrhoids;

[0021] Preferably, in step S1, the amount of sodium alginate added is 3.0-4.0 g, and the amount of sodium carboxymethyl cellulose added is 1.0-2.0 g, wherein sodium alginate has strong adhesion, which can promote the transdermal absorption of the drug at the treatment site and improve the treatment effect, and sodium carboxymethyl cellulose can promote granulation growth and achieve a better hemostatic effect;

[0022] Preferably, in step S2, the amount of tannic acid added is 3.0-5.0 g, and the tannic acid undergoes a cross-linking reaction between the synergistic gel base and the carboxymethyl chitosan modified Chinese medicine liposomes, which not only enhances the stability of the synergistic gel base, but also effectively embeds the liposomes into the gel structure, further enhancing the encapsulation effect of the Chinese medicine ingredients and improving the drug stability. Tannic acid also has astringency, which can induce protein coagulation and vasoconstriction, thereby having a therapeutic effect of promoting hemostasis and prolapse.

[0023] The beneficial effects achieved by the present invention are as follows:

[0024] The present invention forms a liposome gel composite drug-carrying system with a synergistic gel base under the crosslinking of tannic acid through carboxymethyl chitosan modified Chinese medicine liposomes, which has a dual sustained-release effect, significantly enhances the encapsulation effect, helps to improve the stability of the active ingredients, prolongs the retention time of the drug at the treatment site, and effectively improves the therapeutic effect of hemorrhoids; in the carboxymethyl chitosan modified Chinese medicine liposomes, a coated liposome structure is formed, which not only reduces or eliminates the drug exudation caused by the flow of the liposomes, but also reduces the adverse effects of the external environment on the active ingredients, improves the stability of the drug and the liposomes, and at the same time, the presence of the coating film also prolongs the sustained-release time of the embedded substance, thereby prolonging the action time of the drug and helping to enhance the therapeutic effect; in the synergistic gel base, a gel structure with anti-inflammatory, hemostatic and healing-promoting effects is formed, which is applied to the affected part of the hemorrhoids to promote the transdermal absorption of the drug at the affected part, and synergistically enhances the Chinese medicine ingredients. The invention discloses a method for treating hemorrhoids by using carboxymethyl chitosan modified Chinese medicine liposomes, which is stably embedded and distributed in the synergistic gel base structure under the cross-linking effect of tannic acid, wherein the gel structure reduces the fluidity of the liposomes, and forms a double encapsulation of the Chinese medicine liposomes together with the carboxymethyl chitosan, which significantly improves the stability of the drug components and effectively prevents their exudation. At the same time, the presence of the carboxymethyl chitosan modified Chinese medicine liposomes can prevent the sudden release effect of the hydrogel and also endow the composite system with a double sustained-release effect, thereby prolonging the retention time of the drug and improving the therapeutic effectiveness of hemorrhoids. The invention uses carboxymethyl chitosan modified Chinese medicine liposomes, a synergistic gel base, tannic acid, propylene glycol, triethanolamine and sodium methyl paraben to prepare a Chinese medicine composition for treating hemorrhoids, which has a double sustained-release effect and a double encapsulation structure, improves the stability of the active ingredients, prolongs the retention time of the drug at the treatment site, and enhances the therapeutic effect of hemorrhoids. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 This is a scanning electron micrograph of the carboxymethyl chitosan modified Chinese medicine liposome prepared in Example 1 of the present invention;

[0026] Figure 2 This is a scanning electron micrograph of the liposome gel composite drug delivery system prepared in Example 1 of the present invention;

[0027] Figure 3 The encapsulation efficiency results of Examples 1-4 and Comparative Examples 1-3 of the present invention are shown in FIG.

[0028] Figure 4 The particle size distribution results of Examples 1-4 and Comparative Examples 1-3 of the present invention are shown in FIG.

[0029] Figure 5 The graph shows the therapeutic efficacy results of Examples 1-4 and Comparative Examples 1-3 of the present invention. DETAILED DESCRIPTION

[0030] The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments; based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0031] Unless otherwise defined, all professional and scientific terms used herein have the same meanings as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to those described herein may be applied to the present invention. The preferred implementation methods and materials described herein are for demonstration purposes only and are not intended to limit the content of this application.

[0032] The experimental methods in the following examples are conventional methods unless otherwise specified; the experimental materials used in the following examples are purchased from commercial channels unless otherwise specified.

[0033] Tannic acid CAS No: 1401-55-4, brand Innochem, product number A38870;

[0034] Propylene glycol CAS No: 26264-14-2, brand Macklin, product number P967315-500g;

[0035] Triethanolamine CAS No: 102-71-6, brand Aladdin, product number T108154-100ml;

[0036] Chitosan CAS No: 9012-76-4, brand Innochem, product number A41618;

[0037] Sodium methylparaben CAS No: 5026-62-0, brand Innochem, product number A65492;

[0038] Soybean lecithin CAS No: 55128-59-1, brand Sinopharm, item number 69014981;

[0039] Cholesterol CAS No: 57-88-5, brand Innochem, product number A09306;

[0040] Hydrochloric acid CAS No: 7647-01-0, brand Innochem, product number A04558;

[0041] Sodium alginate CAS No: 9005-38-3, brand Innochem, product number A02570;

[0042] Sodium carboxymethyl cellulose CAS No: 9004-32-4, brand Innochem, product number A76272;

[0043] Isopropyl alcohol CAS No: 67-63-0, brand Innochem, product number A75064;

[0044] Chloroacetic acid CAS No: 79-11-8, brand Tci, product number C2123;

[0045] Sodium hydroxide CAS No: 1310-73-2, brand Innochem, product number A36865;

[0046] Anhydrous ethanol CAS No: 64-17-5, brand Innochem, product number G00004.

[0047] Example 1

[0048] This embodiment provides a Chinese medicine composition for treating hemorrhoids, comprising the following components in parts by weight: 60 parts of carboxymethyl chitosan modified Chinese medicine liposomes, 30 parts of synergistic gel base, 10 parts of tannic acid, 3 parts of propylene glycol, 2 parts of triethanolamine, and 1 part of sodium methylparaben.

[0049] The carboxymethyl chitosan modified traditional Chinese medicine liposome comprises the following components in parts by weight: 10 parts of traditional Chinese medicine extract, 50 parts of carboxymethyl chitosan, 20 parts of soybean lecithin and 4 parts of cholesterol.

[0050] The synergistic gel base comprises the following components in parts by weight: 40 parts of sodium alginate and 20 parts of sodium carboxymethyl cellulose.

[0051] The Chinese medicine extract comprises the following components in parts by weight: 5 parts of cinnabar, 5 parts of realgar, 5 parts of red ochre, 5 parts of dragon's blood, 5 parts of myrrh, 5 parts of coptis root, 5 parts of red powder, 5 parts of light powder, 5 parts of borneol and 5 parts of lithospermum.

[0052] The preparation method of carboxymethyl chitosan modified Chinese medicine liposomes specifically comprises the following steps:

[0053] (1) Cinnabar, realgar, red ochre, dragon's blood, myrrh, Sichuan coptis root, red powder, light powder, borneol, and lithospermum officinale are crushed, passed through an 80-mesh sieve, mixed evenly, added with 5 times the amount of distilled water and boiled for 3 times, filtered while hot, combined the filtrate, and then concentrated to 1 / 3 of the original volume of the filtrate, dried, and crushed. Chinese medicinal materials that can promote blood circulation and remove blood stasis, reduce swelling and relieve pain, clear away heat and detoxify, and preserve and promote tissue regeneration are selected, and the purpose of effectively treating hemorrhoids and relieving discomfort symptoms such as bleeding and pain is achieved through the compounding and combination of the medicinal materials, thereby obtaining a Chinese medicinal extract;

[0054] (2) 100 mg of the Chinese herbal extract described in step S1, 200 mg of soybean lecithin, and 40 mg of cholesterol are added to 30 mL of 80% ethanol solution by mass, stirred at constant temperature, slowly injected into the aqueous phase, hydrated at constant temperature, evaporated clean ethanol, ultrasonically crushed, and filtered through a 0.22 μm water membrane. The active ingredients of Chinese herbal medicine such as alkaloids, flavonoids, and polysaccharides not only have significant pharmacological effects, but also form a drug-excipient delivery carrier by co-assembly with traditional liposomes, thereby exerting a stronger efficacy and reducing the occurrence of adverse reactions, thereby obtaining Chinese herbal medicine liposomes;

[0055] (3) Add chitosan to 20 mL of isopropanol solution and react for 4 h. The amount of chitosan added is 0.6 g, which can ensure sufficient reaction with chloroacetic acid, thereby effectively introducing carboxymethyl groups. Then add 25 mL of 30% sodium hydroxide solution and set aside. Weigh 3.0 g of chloroacetic acid and dissolve it in 20 mL of isopropanol solution. Use a magnetic stirrer to slowly pour it into the chitosan solution under stirring conditions. Fully react for 2 h, let it stand for stratification, remove the upper layer solution, take 50 mL of distilled water and add it. Magnetic stirring for 5 min, adjust the pH to 7.0 with 10% hydrochloric acid solution, centrifuge once, and fully precipitate the supernatant with methanol. Centrifuge twice, then add anhydrous ethanol to wash the precipitate. Centrifuge three times. The water solubility of chitosan is improved by modification, and the characteristics of amphoteric polyelectrolyte are given, so that the modified chitosan has good biocompatibility and biodegradability, and a carboxymethyl chitosan solution is obtained.

[0056] (4) The Chinese medicine liposomes described in step (2) are slowly added to the carboxymethyl chitosan solution described in step (3), and the mixed solution is placed in a magnetic stirrer, the temperature is controlled at 50°C, the rotation speed is 20 rpm, and the mixture is stirred for 1 hour, and then intermittent ultrasonic treatment is performed for 20 minutes. During the intermittent ultrasonic treatment, the ultrasonic treatment is performed for 2 minutes and then stopped for 2 minutes. The intermittent application of ultrasound can prevent the coating film from being destroyed under continuous action, which is beneficial to the integrity and protection of the coating film. The Chinese medicine liposomes are modified by carboxymethyl chitosan to form a coated liposome, which can prevent drug leakage, improve the stability of drugs and liposomes, prolong the sustained release time of the embedded substance, and effectively prolong the retention time of the drug, thereby obtaining carboxymethyl chitosan-modified Chinese medicine liposomes.

[0057] This embodiment provides a method for preparing a Chinese medicine composition for treating hemorrhoids, which specifically comprises the following steps:

[0058] S1, dissolve sodium alginate in 80mL water, add sodium carboxymethyl cellulose, stir, the amount of sodium alginate added is 4.0g, the amount of sodium carboxymethyl cellulose added is 2.0g, wherein, sodium alginate has strong adhesion, can promote the transdermal absorption of drugs at the treatment site, improve the therapeutic effect, sodium carboxymethyl cellulose can promote granulation growth, achieve better hemostatic effect, high pressure homogenization, homogenization pressure 800bar, homogenization time 3min, high pressure homogenization is conducive to the uniformity of distribution of sodium alginate and sodium carboxymethyl cellulose, and also contributes to better cross-linking effect in the follow-up, then heat in a water bath at 40°C, stirring speed 500rpm, stirring time 30min, so that sodium alginate and sodium carboxymethyl cellulose molecules are cross-linked to form a gel network structure, which has the effect of film-forming and absorbing water, and is applied to the affected area of ​​hemorrhoids, which can provide a moist environment to prevent bacterial growth, and can also play the anti-inflammatory, hemostatic and healing effects of the gel components to promote the healing of ruptured wounds, to obtain a synergistic gel base;

[0059] S2, adding carboxymethyl chitosan modified Chinese medicine liposomes to the synergistic gel base described in step S1, stirring evenly, and then adding tannic acid, the amount of tannic acid added is 5.0g, tannic acid cross-linking reaction between the synergistic gel base and the carboxymethyl chitosan modified Chinese medicine liposomes, not only enhances the stability of the synergistic gel base, but also effectively embeds the liposomes into the gel structure, further enhances the encapsulation effect of the Chinese medicine ingredients, improves the drug stability, and tannic acid also has astringency, can induce protein coagulation and vasoconstriction, thereby promoting hemostasis and prolapse treatment. The mixture was stirred for 25 minutes, the pH was adjusted to 6.0, and heated in a water bath at a temperature of 50°C for 2 hours. The carboxymethyl chitosan-modified Chinese medicine liposomes were distributed in the synergistic gel base structure to reduce the fluidity of the liposomes, protect the integrity and stability of the active ingredients, and effectively prevent the drug from seeping out and leaking. At the same time, the presence of the liposomes can prevent the sudden release effect of the hydrogel and also give the composite system a dual sustained-release effect, thereby prolonging the retention time of the drug and improving the therapeutic effect on hemorrhoids, thereby obtaining a liposome gel composite drug-carrying system.

[0060] S3, adding propylene glycol to the liposome gel composite drug delivery system described in step S2, magnetic stirring for 10 minutes, then adding triethanolamine and sodium methylparaben, stirring evenly to form a composite gel, wherein propylene glycol helps other components to be dispersed into the liposome gel composite drug delivery system, triethanolamine is beneficial to improving the gel performance, and sodium methylparaben enhances the antibacterial property, reduces the bacterial infection of the hemorrhoid diseased site, and obtains the Chinese medicine composition for treating hemorrhoids.

[0061] In this example, the prepared carboxymethyl chitosan modified Chinese medicine liposomes and liposome gel composite drug delivery system were subjected to scanning electron microscopy to observe their microscopic morphology. Figure 1 This is a SEM image of the carboxymethyl chitosan modified Chinese medicine liposome prepared in Example 1, magnified 100,000 times. Figure 2 This is a SEM image of the liposome gel composite drug delivery system prepared in Example 1 magnified 400 times. Figure 1 The carboxymethyl chitosan modified Chinese medicine liposome prepared in this embodiment is a coated liposome, such as Figure 2 The liposome gel composite drug delivery system prepared in this embodiment is a gel structure loaded with liposomes.

[0062] Example 2

[0063] This embodiment provides a Chinese medicine composition for treating hemorrhoids, comprising the following components in parts by weight: 50 parts of carboxymethyl chitosan modified Chinese medicine liposomes, 20 parts of synergistic gel base, 6 parts of tannic acid, 2 parts of propylene glycol, 1 part of triethanolamine, and 0.5 parts of sodium methylparaben.

[0064] The carboxymethyl chitosan modified traditional Chinese medicine liposome comprises the following components in parts by weight: 8 parts of traditional Chinese medicine extract, 40 parts of carboxymethyl chitosan, 18 parts of soybean lecithin and 3 parts of cholesterol.

[0065] The synergistic gel base comprises the following components in parts by weight: 30 parts of sodium alginate and 10 parts of sodium carboxymethyl cellulose.

[0066] The Chinese medicine extract comprises the following components in parts by weight: 3 parts of cinnabar, 3 parts of realgar, 3 parts of red ochre, 3 parts of dragon's blood, 3 parts of myrrh, 3 parts of coptis root, 3 parts of red powder, 3 parts of light powder, 3 parts of borneol and 3 parts of lithospermum.

[0067] The preparation method of carboxymethyl chitosan modified Chinese medicine liposomes specifically comprises the following steps:

[0068] (1) Cinnabar, realgar, red ochre, dragon's blood, myrrh, Sichuan coptis root, red powder, light powder, borneol, and lithospermum officinale are crushed, passed through a 60-mesh sieve, mixed evenly, added with 3 times the amount of distilled water and boiled twice, filtered while hot, combined the filtrate, and then concentrated to 1 / 5 of the original volume of the filtrate, dried, and crushed. Chinese medicinal materials that can promote blood circulation and remove blood stasis, reduce swelling and relieve pain, clear away heat and detoxify, and preserve and promote tissue regeneration are selected, and the purpose of effectively treating hemorrhoids and relieving discomfort symptoms such as bleeding and pain is achieved through the compounding and combination of the medicinal materials to obtain a Chinese medicinal extract;

[0069] (2) 80 mg of the Chinese herbal extract described in step S1, 180 mg of soybean lecithin, and 30 mg of cholesterol are added to 20 mL of 80% ethanol solution by mass, stirred at a constant temperature, slowly injected into the aqueous phase, hydrated at a constant temperature, evaporated clean ethanol, ultrasonically crushed, and filtered through a 0.22 μm water membrane. The active ingredients of Chinese herbal medicine such as alkaloids, flavonoids, and polysaccharides not only have significant pharmacological effects, but also form a drug-excipient delivery carrier by co-assembly with traditional liposomes, thereby exerting a stronger efficacy and reducing the occurrence of adverse reactions, thereby obtaining Chinese herbal medicine liposomes;

[0070] (3) Add chitosan to 20 mL of isopropanol solution and react for 3 h. The amount of chitosan added is 0.5 g, which can ensure sufficient reaction with chloroacetic acid, thereby effectively introducing carboxymethyl groups. Then add 25 mL of 30% sodium hydroxide solution and set aside. Weigh 3.0 g of chloroacetic acid and dissolve it in 20 mL of isopropanol solution. Use a magnetic stirrer to slowly pour it into the chitosan solution under stirring conditions. Fully react for 1 h, let it stand for stratification, remove the upper layer solution, take 50 mL of distilled water and add it. Stir magnetically for 5 min. Adjust the pH to 7.0 with 10% hydrochloric acid solution. Centrifuge once, and fully precipitate the supernatant with methanol. Centrifuge twice, then add anhydrous ethanol to wash the precipitate. Centrifuge three times. The water solubility of chitosan is improved by modification, and the characteristics of amphoteric polyelectrolyte are given, so that the modified chitosan has good biocompatibility and biodegradability, and a carboxymethyl chitosan solution is obtained.

[0071] (4) The Chinese medicine liposomes described in step (2) are slowly added to the carboxymethyl chitosan solution described in step (3), and the mixed solution is placed in a magnetic stirrer, the temperature is controlled at 40°C, the rotation speed is 10 rpm, and the mixture is stirred for 0.5 h, and then intermittent ultrasonic treatment is performed for 10 min. During the intermittent ultrasonic treatment, the ultrasonic treatment is performed for 2 min and then stopped for 2 min. The intermittent application of ultrasound can prevent the coating film from being destroyed under continuous action, which is beneficial to the integrity and protection of the coating film. The Chinese medicine liposomes are modified by carboxymethyl chitosan to form a coated liposome, which can prevent drug leakage, improve the stability of drugs and liposomes, prolong the sustained release time of the embedded substance, and effectively prolong the retention time of the drug, thereby obtaining carboxymethyl chitosan-modified Chinese medicine liposomes.

[0072] This embodiment provides a method for preparing a Chinese medicine composition for treating hemorrhoids, which specifically comprises the following steps:

[0073] S1, dissolving sodium alginate in 80mL water, adding sodium carboxymethyl cellulose, stirring, the amount of sodium alginate added is 3.0g, the amount of sodium carboxymethyl cellulose added is 1.0g, wherein, sodium alginate has strong adhesion, can promote the transdermal absorption of drugs at the treatment site, improve the therapeutic effect, sodium carboxymethyl cellulose can promote granulation growth, achieve better hemostatic effect, high pressure homogenization, homogenization pressure 600bar, homogenization time 1min, high pressure homogenization is conducive to the uniformity of distribution of sodium alginate and sodium carboxymethyl cellulose, and also contributes to better cross-linking effect in the follow-up, then heating in a water bath at 30°C, stirring speed 400rpm, stirring time 20min, so that sodium alginate and sodium carboxymethyl cellulose molecules are cross-linked to form a gel network structure, which has the effect of film-forming and absorbing water, and is applied to the affected area of ​​hemorrhoids, can provide a moist environment, prevent bacterial growth, and can also play the anti-inflammatory, hemostatic and healing effects of the gel components to promote the rupture of the wound, to obtain a synergistic gel base;

[0074] S2, adding carboxymethyl chitosan modified Chinese medicine liposomes to the synergistic gel base described in step S1, stirring evenly, and then adding tannic acid, the amount of tannic acid added is 3.0g, tannic acid cross-linking reaction between the synergistic gel base and the carboxymethyl chitosan modified Chinese medicine liposomes, not only enhances the stability of the synergistic gel base, but also effectively embeds the liposomes into the gel structure, further enhances the encapsulation effect of the Chinese medicine ingredients, improves the drug stability, and tannic acid also has astringency, can induce protein coagulation and vasoconstriction, thereby promoting hemostasis and prolapse treatment. The mixture was stirred for 15 minutes, the pH was adjusted to 5.0, and the mixture was heated in a water bath at a temperature of 40°C for 1 hour. The carboxymethyl chitosan-modified Chinese medicine liposomes were distributed in the synergistic gel base structure to reduce the fluidity of the liposomes, protect the integrity and stability of the active ingredients, and effectively prevent the drug from seeping out and leaking. At the same time, the presence of the liposomes can prevent the sudden release effect of the hydrogel and also give the composite system a dual sustained-release effect, thereby prolonging the retention time of the drug and improving the therapeutic effect on hemorrhoids, thereby obtaining a liposome gel composite drug-carrying system.

[0075] S3, adding propylene glycol to the liposome gel composite drug delivery system described in step S2, magnetic stirring for 10 minutes, then adding triethanolamine and sodium methylparaben, stirring evenly to form a composite gel, wherein propylene glycol helps other components to be dispersed into the liposome gel composite drug delivery system, triethanolamine is beneficial to improving the gel performance, and sodium methylparaben enhances the antibacterial property, reduces the bacterial infection of the hemorrhoid diseased site, and obtains the Chinese medicine composition for treating hemorrhoids.

[0076] Example 3

[0077] This embodiment provides a Chinese medicine composition for treating hemorrhoids, comprising the following components in parts by weight: 55 parts of carboxymethyl chitosan modified Chinese medicine liposomes, 25 parts of synergistic gel base, 8 parts of tannic acid, 2.5 parts of propylene glycol, 1.5 parts of triethanolamine, and 0.75 parts of sodium methylparaben.

[0078] The carboxymethyl chitosan modified traditional Chinese medicine liposome comprises the following components in parts by weight: 9 parts of traditional Chinese medicine extract, 45 parts of carboxymethyl chitosan, 19 parts of soybean lecithin and 3.5 parts of cholesterol.

[0079] The synergistic gel base comprises the following components in parts by weight: 35 parts of sodium alginate and 15 parts of sodium carboxymethyl cellulose.

[0080] The Chinese medicine extract comprises the following components in parts by weight: 4 parts of cinnabar, 4 parts of realgar, 4 parts of red ochre, 4 parts of dragon's blood, 4 parts of myrrh, 4 parts of coptis root, 4 parts of red powder, 4 parts of light powder, 4 parts of borneol and 4 parts of lithospermum.

[0081] The preparation method of carboxymethyl chitosan modified Chinese medicine liposomes specifically comprises the following steps:

[0082] (1) Cinnabar, realgar, red ochre, dragon's blood, myrrh, Sichuan coptis root, red powder, light powder, borneol, and lithospermum officinale are crushed, passed through a 70-mesh sieve, mixed evenly, added with 4 times the amount of distilled water and boiled twice, filtered while hot, combined the filtrate, and then concentrated to 1 / 3 of the original volume of the filtrate, dried, and crushed. Chinese medicinal materials that can promote blood circulation and remove blood stasis, reduce swelling and relieve pain, clear away heat and detoxify, and preserve and promote tissue regeneration are selected, and the purpose of effectively treating hemorrhoids and relieving discomfort symptoms such as bleeding and pain is achieved through the compounding and combination of the medicinal materials.

[0083] (2) 90 mg of the Chinese herbal extract described in step S1, 190 mg of soybean lecithin, and 35 mg of cholesterol are added to 25 mL of 80% ethanol solution by mass, stirred at a constant temperature, slowly injected into the aqueous phase, hydrated at a constant temperature, evaporated clean ethanol, ultrasonically crushed, and filtered through a 0.22 μm water membrane. The active ingredients of Chinese herbal medicine such as alkaloids, flavonoids, and polysaccharides not only have significant pharmacological effects, but also form a drug-excipient delivery carrier by co-assembly with traditional liposomes, thereby exerting a stronger efficacy and reducing the occurrence of adverse reactions, thereby obtaining Chinese herbal medicine liposomes;

[0084] (3) Add chitosan to 20 mL of isopropanol solution and react for 3.5 h. The amount of chitosan added is 0.55 g, which can ensure sufficient reaction with chloroacetic acid, thereby effectively introducing carboxymethyl groups. Then add 25 mL of 30% sodium hydroxide solution and set aside. Weigh 3.0 g of chloroacetic acid and dissolve it in 20 mL of isopropanol solution. Use a magnetic stirrer to slowly pour it into the chitosan solution under stirring conditions. Fully react for 1.5 h, let it stand for stratification, remove the upper layer solution, take 50 mL of distilled water and add it. Stir magnetically for 5 min. Adjust the pH to 7.0 with 10% hydrochloric acid solution. Centrifuge once, and fully precipitate the supernatant with methanol. Centrifuge twice, then add anhydrous ethanol to wash the precipitate. Centrifuge three times. The water solubility of chitosan is improved by modification, and the characteristics of amphoteric polyelectrolyte are given, so that the modified chitosan has good biocompatibility and biodegradability, and a carboxymethyl chitosan solution is obtained.

[0085] (4) The Chinese medicine liposomes described in step (2) are slowly added to the carboxymethyl chitosan solution described in step (3), and the mixed solution is placed in a magnetic stirrer, the temperature is controlled at 45°C, the rotation speed is 15 rpm, and the mixture is stirred for 0.75 h, and then intermittent ultrasonic treatment is performed for 15 min. During the intermittent ultrasonic treatment, the ultrasonic treatment is performed for 2 min and then stopped for 2 min. The intermittent application of ultrasound can prevent the coating film from being destroyed under continuous action, which is beneficial to the integrity and protection of the coating film. The Chinese medicine liposomes are modified by carboxymethyl chitosan to form a coated liposome, which can prevent drug leakage, improve the stability of drugs and liposomes, prolong the sustained release time of the embedded substance, and effectively prolong the retention time of the drug, thereby obtaining carboxymethyl chitosan-modified Chinese medicine liposomes.

[0086] This embodiment provides a method for preparing a Chinese medicine composition for treating hemorrhoids, which specifically comprises the following steps:

[0087] S1, dissolving sodium alginate in 80mL water, adding sodium carboxymethyl cellulose, stirring, the amount of sodium alginate added is 3.5g, the amount of sodium carboxymethyl cellulose added is 1.5g, wherein, sodium alginate has strong adhesion, can promote the transdermal absorption of drugs at the treatment site, improve the therapeutic effect, sodium carboxymethyl cellulose can promote granulation growth, achieve better hemostatic effect, high pressure homogenization, homogenization pressure 700bar, homogenization time 2min, high pressure homogenization is conducive to the uniformity of distribution of sodium alginate and sodium carboxymethyl cellulose, and also contributes to better cross-linking effect in the follow-up, then heating in a water bath at 35°C, stirring speed 450rpm, stirring time 25min, so that sodium alginate and sodium carboxymethyl cellulose molecules are cross-linked to form a gel network structure, which has the effect of film-forming and absorbing water, and is applied to the affected area of ​​hemorrhoids, which can provide a moist environment to prevent bacterial growth, and can also play the anti-inflammatory, hemostatic and healing effects of the gel components to promote the rupture of wounds, to obtain a synergistic gel base;

[0088] S2. Add carboxymethyl chitosan modified Chinese medicine liposomes to the synergistic gel base described in step S1, stir evenly, and then add tannic acid, the amount of tannic acid added is 4.0g. Tannic acid undergoes a cross-linking reaction between the synergistic gel base and the carboxymethyl chitosan modified Chinese medicine liposomes, which not only enhances the stability of the synergistic gel base, but also effectively embeds the liposomes into the gel structure, further enhancing the encapsulation effect of the Chinese medicine ingredients and improving the drug stability. Tannic acid also has astringency, which can induce protein coagulation and vasoconstriction, thereby promoting the treatment of hemostasis and prolapse. The mixture was stirred for 20 minutes, the pH was adjusted to 5.5, and the mixture was heated in a water bath at a temperature of 45°C for 1.5 hours. The carboxymethyl chitosan-modified Chinese medicine liposomes were distributed in the synergistic gel base structure to reduce the fluidity of the liposomes, protect the integrity and stability of the active ingredients, and effectively prevent the drug from seeping out and leaking. At the same time, the presence of the liposomes can prevent the sudden release effect of the hydrogel and also give the composite system a dual sustained-release effect, thereby prolonging the retention time of the drug and improving the therapeutic effect on hemorrhoids, thereby obtaining a liposome gel composite drug-carrying system.

[0089] S3, adding propylene glycol to the liposome gel composite drug delivery system described in step S2, magnetic stirring for 10 minutes, then adding triethanolamine and sodium methylparaben, stirring evenly to form a composite gel, wherein propylene glycol helps other components to be dispersed into the liposome gel composite drug delivery system, triethanolamine is beneficial to improving the gel performance, and sodium methylparaben enhances the antibacterial property, reduces the bacterial infection of the hemorrhoid diseased site, and obtains the Chinese medicine composition for treating hemorrhoids.

[0090] Example 4

[0091] This embodiment provides a Chinese medicine composition for treating hemorrhoids, comprising the following components in parts by weight: 50 parts of carboxymethyl chitosan modified Chinese medicine liposomes, 30 parts of synergistic gel base, 6 parts of tannic acid, 3 parts of propylene glycol, 2 parts of triethanolamine, and 1 part of sodium methylparaben.

[0092] The carboxymethyl chitosan modified traditional Chinese medicine liposome comprises the following components in parts by weight: 10 parts of traditional Chinese medicine extract, 40 parts of carboxymethyl chitosan, 20 parts of soybean lecithin and 4 parts of cholesterol.

[0093] The synergistic gel base comprises the following components in parts by weight: 40 parts of sodium alginate and 20 parts of sodium carboxymethyl cellulose.

[0094] The Chinese medicine extract comprises the following components in parts by weight: 5 parts of cinnabar, 5 parts of realgar, 5 parts of red ochre, 3 parts of dragon's blood, 3 parts of myrrh, 5 parts of coptis root, 5 parts of red powder, 3 parts of light powder, 3 parts of borneol and 3 parts of lithospermum.

[0095] The preparation method of carboxymethyl chitosan modified Chinese medicine liposomes specifically comprises the following steps:

[0096] (1) Cinnabar, realgar, red ochre, dragon's blood, myrrh, Sichuan coptis root, red powder, light powder, borneol, and lithospermum officinale are crushed, passed through an 80-mesh sieve, mixed evenly, added with 5 times the amount of distilled water and boiled for 3 times, filtered while hot, combined the filtrate, and then concentrated to 1 / 5 of the original volume of the filtrate, dried, and crushed. Chinese medicinal materials that can promote blood circulation and remove blood stasis, reduce swelling and relieve pain, clear away heat and detoxify, and preserve and promote tissue regeneration are selected, and the purpose of effectively treating hemorrhoids and relieving discomfort symptoms such as bleeding and pain is achieved through the compounding and combination of the medicinal materials to obtain a Chinese medicinal extract;

[0097] (2) 100 mg of the Chinese herbal extract described in step S1, 200 mg of soybean lecithin, and 40 mg of cholesterol are added to 30 mL of 80% ethanol solution by mass, stirred at constant temperature, slowly injected into the aqueous phase, hydrated at constant temperature, evaporated clean ethanol, ultrasonically crushed, and filtered through a 0.22 μm water membrane. The active ingredients of Chinese herbal medicine such as alkaloids, flavonoids, and polysaccharides not only have significant pharmacological effects, but also form a drug-excipient delivery carrier by co-assembly with traditional liposomes, thereby exerting a stronger efficacy and reducing the occurrence of adverse reactions, thereby obtaining Chinese herbal medicine liposomes;

[0098] (3) Add chitosan to 20 mL of isopropanol solution and react for 3 h. The amount of chitosan added is 0.5 g, which can ensure sufficient reaction with chloroacetic acid, thereby effectively introducing carboxymethyl groups. Then add 25 mL of 30% sodium hydroxide solution and set aside. Weigh 3.0 g of chloroacetic acid and dissolve it in 20 mL of isopropanol solution. Use a magnetic stirrer to slowly pour it into the chitosan solution under stirring conditions. Fully react for 1 h, let it stand for stratification, remove the upper layer solution, take 50 mL of distilled water and add it. Stir magnetically for 5 min. Adjust the pH to 7.0 with 10% hydrochloric acid solution. Centrifuge once, and fully precipitate the supernatant with methanol. Centrifuge twice, then add anhydrous ethanol to wash the precipitate. Centrifuge three times. The water solubility of chitosan is improved by modification, and the characteristics of amphoteric polyelectrolyte are given, so that the modified chitosan has good biocompatibility and biodegradability, and a carboxymethyl chitosan solution is obtained.

[0099] (4) The Chinese medicine liposomes described in step (2) are slowly added to the carboxymethyl chitosan solution described in step (3), and the mixed solution is placed in a magnetic stirrer, the temperature is controlled at 50°C, the rotation speed is 20 rpm, and the mixture is stirred for 0.5 h, and then intermittent ultrasonic treatment is performed for 10 min. During the intermittent ultrasonic treatment, the ultrasonic treatment is performed for 2 min and then stopped for 2 min. The intermittent application of ultrasound can prevent the coating film from being destroyed under continuous action, which is beneficial to the integrity and protection of the coating film. The Chinese medicine liposomes are modified by carboxymethyl chitosan to form a coated liposome, which can prevent drug leakage, improve the stability of drugs and liposomes, prolong the sustained release time of the embedded substance, and effectively prolong the retention time of the drug, thereby obtaining carboxymethyl chitosan-modified Chinese medicine liposomes.

[0100] This embodiment provides a method for preparing a Chinese medicine composition for treating hemorrhoids, which specifically comprises the following steps:

[0101] S1, dissolving sodium alginate in 80mL water, adding sodium carboxymethyl cellulose, stirring, the amount of sodium alginate added is 4.0g, the amount of sodium carboxymethyl cellulose added is 2.0g, wherein, sodium alginate has strong adhesion, can promote the transdermal absorption of drugs at the treatment site, improve the therapeutic effect, sodium carboxymethyl cellulose can promote granulation growth, achieve better hemostatic effect, high pressure homogenization, homogenization pressure 800bar, homogenization time 1min, high pressure homogenization is conducive to the uniformity of distribution of sodium alginate and sodium carboxymethyl cellulose, and also contributes to better cross-linking effect in the follow-up, then heating in a water bath at 40°C, stirring speed 500rpm, stirring time 20min, so that sodium alginate and sodium carboxymethyl cellulose molecules are cross-linked to form a gel network structure, which has the effect of film-forming and absorbing water, and is applied to the affected area of ​​hemorrhoids, can provide a moist environment, prevent bacterial growth, and can also play the anti-inflammatory, hemostatic and healing effects of the gel components to promote the rupture of the wound, to obtain a synergistic gel base;

[0102] S2, adding carboxymethyl chitosan modified Chinese medicine liposomes to the synergistic gel base described in step S1, stirring evenly, and then adding tannic acid, the amount of tannic acid added is 3.0g, tannic acid cross-linking reaction between the synergistic gel base and the carboxymethyl chitosan modified Chinese medicine liposomes, not only enhances the stability of the synergistic gel base, but also effectively embeds the liposomes into the gel structure, further enhances the encapsulation effect of the Chinese medicine ingredients, improves the drug stability, and tannic acid also has astringency, can induce protein coagulation and vasoconstriction, thereby promoting hemostasis and prolapse treatment. The mixture was stirred for 15 minutes, the pH was adjusted to 6.0, and heated in a water bath at a temperature of 50°C for 1 hour. The carboxymethyl chitosan-modified Chinese medicine liposomes were distributed in the synergistic gel base structure to reduce the fluidity of the liposomes, protect the integrity and stability of the active ingredients, and effectively prevent the drug from seeping out and leaking. At the same time, the presence of the liposomes can prevent the sudden release effect of the hydrogel and also give the composite system a dual sustained-release effect, thereby prolonging the retention time of the drug and improving the therapeutic effect on hemorrhoids, thereby obtaining a liposome gel composite drug-carrying system.

[0103] S3, adding propylene glycol to the liposome gel composite drug delivery system described in step S2, magnetic stirring for 10 minutes, then adding triethanolamine and sodium methylparaben, stirring evenly to form a composite gel, wherein propylene glycol helps other components to be dispersed into the liposome gel composite drug delivery system, triethanolamine is beneficial to improving the gel performance, and sodium methylparaben enhances the antibacterial property, reduces the bacterial infection of the hemorrhoid diseased site, and obtains the Chinese medicine composition for treating hemorrhoids.

[0104] Comparative Example 1

[0105] This comparative example provides a Chinese medicine composition for treating hemorrhoids, which differs from Example 1 in that the carboxymethyl chitosan-modified Chinese medicine liposome does not contain carboxymethyl chitosan; the preparation method of the carboxymethyl chitosan-modified Chinese medicine liposome does not include step (3); and the preparation method of the Chinese medicine composition for treating hemorrhoids is the same as that of Example 1.

[0106] Comparative Example 2

[0107] This comparative example provides a Chinese medicine composition for treating hemorrhoids, which is different from Example 1 in that the Chinese medicine composition for treating hemorrhoids does not contain a synergistic gel base; the preparation method of carboxymethyl chitosan modified Chinese medicine liposomes is the same as that of Example 1; and the preparation method of the Chinese medicine composition for treating hemorrhoids does not include step S1.

[0108] Comparative Example 3

[0109] This comparative example provides a Chinese medicine composition for treating hemorrhoids, which differs from Example 1 in that the Chinese medicine composition for treating hemorrhoids does not contain tannic acid; the preparation method of carboxymethyl chitosan modified Chinese medicine liposomes is the same as that of Example 1; and the preparation method of the Chinese medicine composition for treating hemorrhoids does not include step S2.

[0110] Experimental Example 1

[0111] Encapsulation efficiency experiment

[0112] Test sample: the Chinese medicinal composition for treating hemorrhoids prepared in Examples 1-4 and Comparative Examples 1-3.

[0113] Test method: accurately weigh 1g / mL of Chinese herbal medicine and dilute it to 20mg / mL, use distilled water as blank, use UV spectrophotometer to scan in the wavelength range of 330-500nm, and the maximum absorption is at 350nm; then dilute the Chinese herbal medicine into 0-20mg / mL drug solution, measure the absorbance A at 350nm, and get the standard curve equation A=0.1078C+0.0215 by regression, r 2 =0.9938, the best linear range is 2-8 mg / mL; 0.5 g of the test sample was dissolved in 1 mL of methanol solution, vortexed for 1 h and stirred to ensure full extraction of the drug, and then centrifuged at 10000 rpm for 10 min after standing for 1 h. The filtrate was filtered with a 0.22 μm filter, the concentration of the Chinese medicine was determined, the total amount of the Chinese medicine and the amount of free Chinese medicine were calculated, and the encapsulation rate (%) was calculated according to the following formula:

[0114] Encapsulation rate (%) = (total amount of Chinese medicine - free amount of Chinese medicine) / total amount of Chinese medicine × 100%

[0115] Figure 3It is a graph of the encapsulation rate results of Examples 1-4 and Comparative Examples 1-3; as shown in the figure, the encapsulation rates of Examples 1-4 are 85.4-88.7%, indicating that the encapsulation is good; the encapsulation rates of Comparative Examples 1-3 are 71.3-78.2%, indicating that the encapsulation is poor; the carboxymethyl chitosan-modified Chinese medicine liposomes of Comparative Example 1 do not contain carboxymethyl chitosan, and cannot form a coated liposome structure, resulting in poor encapsulation; the Chinese medicine composition for treating hemorrhoids of Comparative Example 2 does not contain a synergistic gel base, and cannot form an encapsulation around the coated liposome structure again, resulting in poor encapsulation; the Chinese medicine composition for treating hemorrhoids of Comparative Example 3 does not contain tannic acid, which is not conducive to the stability of double encapsulation, resulting in poor encapsulation.

[0116] Experimental Example 2

[0117] Stability test

[0118] Test sample: the Chinese medicinal composition for treating hemorrhoids prepared in Examples 1-4 and Comparative Examples 1-3.

[0119] Test method: Store the test sample at room temperature for 14 days, measure the particle size with a nano-particle size potentiometer, and calculate the particle size distribution after 14 days.

[0120] Figure 4 The particle size distribution results of Examples 1-4 and Comparative Examples 1-3 are shown in FIG. 5 ; as shown in the figure, the particle size distribution of Examples 1-4 in the range of <70nm, 70-80nm, 80-90nm, 90-100nm and >100nm is 5-6%, 15-20%, 50-60%, 10-19%, and 5-10%, respectively, indicating that the particle size is concentrated in 70-100nm, and the proportion of particles greater than 100nm is small, and the stability is good; the particle size distribution of Comparative Examples 1-3 in the range of <70nm, 70-80nm, 80-90nm, 90-100nm and >100nm is 5-6%, 6-12%, 40-46%, 22-28%, 15-20 %, indicating that the proportion of particles larger than 100 nm increases, the particle size changes significantly, and the stability is poor; the carboxymethyl chitosan-modified traditional Chinese medicine liposomes in comparative example 1 do not contain carboxymethyl chitosan, which reduces the stability of the liposome structure, resulting in significant changes in particle size and poor stability; the traditional Chinese medicine composition for treating hemorrhoids in comparative example 2 does not contain a synergistic gel base, which is not conducive to reducing the fluidity of the liposomes and has an adverse effect on their stability, resulting in significant changes in particle size and poor stability; the traditional Chinese medicine composition for treating hemorrhoids in comparative example 3 does not contain tannic acid, which is not conducive to the stability of the embedded distribution of carboxymethyl chitosan-modified traditional Chinese medicine liposomes in the synergistic gel base structure, thereby being not conducive to the stability of the liposome structure, resulting in significant changes in particle size and poor stability.

[0121] Experimental Example 3

[0122] Treatment efficacy experiment

[0123] Test sample: the Chinese medicinal composition for treating hemorrhoids prepared in Examples 1-4 and Comparative Examples 1-3.

[0124] Test method: 140 patients with different degrees of internal hemorrhoids, external hemorrhoids, and mixed hemorrhoids were selected, with specific symptoms such as bleeding, prolapse, swelling, pain, etc., and their ages ranged from 30 to 60 years old. They were enrolled using a random number table and divided into 7 groups, each with 20 patients. Each group used the corresponding test sample. The method of taking the test sample was to apply the test sample to the affected area twice a day, and the effect was observed after 30 days. At the same time, the treatment effect was determined according to the following standards, and the treatment effectiveness rate (%) was calculated, specifically:

[0125] Effective: Hemorrhoid symptoms completely disappeared, hemorrhoid symptoms changed from severe to moderate, from moderate to mild, and from mild to normal;

[0126] Ineffective: There was no significant improvement in hemorrhoidal symptoms.

[0127] The formula for calculating the treatment effectiveness is as follows:

[0128] Treatment effectiveness (%) = effective number of people / 20×100%

[0129] Figure 5 It is a therapeutic efficacy result diagram of Examples 1-4 and Comparative Examples 1-3; as shown in the figure, the therapeutic efficacy of Examples 1-4 is 80-95%, indicating that the therapeutic effect is better; the therapeutic efficacy of Comparative Examples 1-3 is 65-75%, indicating that the therapeutic effect is average; the carboxymethyl chitosan-modified Chinese medicine liposome of Comparative Example 1 does not contain carboxymethyl chitosan, which is not conducive to the encapsulation stability of the drug and is not conducive to prolonging the action time of the drug, resulting in average therapeutic effect; the Chinese medicine composition for treating hemorrhoids in Comparative Example 2 does not contain a synergistic gel base, cannot form double encapsulation, and does not have a dual sustained-release effect, which is not conducive to prolonging the retention time of the drug, resulting in average therapeutic effect; the Chinese medicine composition for treating hemorrhoids in Comparative Example 3 does not contain tannic acid, which is not conducive to the stability of the combination of carboxymethyl chitosan-modified Chinese medicine liposomes and the synergistic gel base, increases the risk of sudden release of the gel, and results in average therapeutic effect.

[0130] The above experimental results show that the encapsulation rate, stability and therapeutic effect of Examples 1-4 of the present invention are significantly better than those of Comparative Examples 1-3. Among them, the encapsulation rate and stability of Example 1 using carboxymethyl chitosan-modified Chinese medicine liposomes and a synergistic gel base are better, and the therapeutic effect is better. The carboxymethyl chitosan-modified Chinese medicine liposomes form a coated liposome structure, which not only reduces or eliminates the drug exudation caused by the flow of liposomes, but also reduces the adverse effects of the external environment on the active ingredients, improves the stability of the drug and liposomes, and at the same time, prolongs the sustained release time of the embedded substance, thereby prolonging the action time of the drug and helping to enhance the therapeutic effect; under the cross-linking action of tannic acid, the carboxymethyl chitosan-modified Chinese medicine liposomes are stably embedded and distributed in the synergistic gel base structure, forming a double encapsulation of the Chinese medicine liposomes, significantly improving the stability of the drug ingredients, and also giving the composite system a dual sustained release effect, prolonging the retention time of the drug, and improving the effectiveness of the treatment of hemorrhoids.

[0131] While the embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that many changes, modifications, substitutions and variations can be made to the embodiments without departing from the principles and spirit of the invention.

[0132] The present invention and its implementation methods are described above, which is not restrictive. The drawings are only one of the implementation methods of the present invention, and the actual application is not limited thereto. In short, if ordinary technicians in the field are inspired by it and design methods and embodiments similar to the technical solution without creativity without departing from the purpose of the invention, they should all fall within the protection scope of the present invention.

Claims

1. A Chinese medicine composition for treating hemorrhoids, characterized in that: The Chinese medicine composition for treating hemorrhoids comprises the following components in parts by weight: 50-60 parts of carboxymethyl chitosan modified Chinese medicine liposomes, 20-30 parts of synergistic gel base, 6-10 parts of tannic acid, 2-3 parts of propylene glycol, 1-2 parts of triethanolamine, and 0.5-1 parts of sodium methyl paraben; the carboxymethyl chitosan modified Chinese medicine liposomes comprises the following components in parts by weight: 8-10 parts of Chinese medicine extract, 40-50 parts of carboxymethyl chitosan, 10 parts of soybean lecithin, 10 parts of glycerol, 10 parts of sodium hydroxyethyl ester ... 8-20 parts, cholesterol 3-4 parts; the synergistic gel base comprises the following components in parts by weight: 30-40 parts of sodium alginate, 10-20 parts of sodium carboxymethyl cellulose; the raw materials of the traditional Chinese medicine extract include the following components in parts by weight: 3-5 parts of cinnabar, 3-5 parts of realgar, 3-5 parts of red ochre, 3-5 parts of dragon's blood, 3-5 parts of myrrh, 3-5 parts of Sichuan coptis, 3-5 parts of red powder, 3-5 parts of light powder, 3-5 parts of borneol, and 3-5 parts of lithospermum.

2. A method for preparing a Chinese medicine composition for treating hemorrhoids according to claim 1, characterized in that: The specific steps include: S1. Dissolve sodium alginate in 80 mL of water, add sodium carboxymethyl cellulose, stir, homogenize under high pressure, homogenize at a pressure of 600-800 bar, homogenize for 1-3 min, then heat in a water bath at 30-40° C., stir at a speed of 400-500 rpm, and stir for 20-30 min to obtain a synergistic gel base; S2, adding carboxymethyl chitosan modified Chinese medicine liposomes to the synergistic gel base described in step S1, stirring evenly, then adding tannic acid, stirring for 15-25 minutes, adjusting the pH to 5.0-6.0, heating in a water bath, controlling the temperature at 40-50° C., heating time 1-2 hours, to obtain a liposome gel composite drug delivery system; S3, adding propylene glycol to the liposome gel composite drug delivery system described in step S2, magnetic stirring for 10 minutes, and then adding triethanolamine and sodium methylparaben, stirring evenly to form a composite gel, thereby obtaining a traditional Chinese medicine composition for treating hemorrhoids.

3. The method for preparing the Chinese medicine composition for treating hemorrhoids according to claim 2, wherein: In step S1, the amount of sodium alginate added is 3.0-4.0 g, and the amount of sodium carboxymethyl cellulose added is 1.0-2.0 g.

4. The method for preparing the Chinese medicine composition for treating hemorrhoids according to claim 3, wherein: In step S2, the amount of tannic acid added is 3.0-5.0 g.

5. The method for preparing the Chinese medicine composition for treating hemorrhoids according to claim 4, characterized in that: The method for preparing the carboxymethyl chitosan modified Chinese medicine liposome specifically comprises the following steps: (1) Crush cinnabar, realgar, red ochre, dragon's blood, myrrh, coptis root, red powder, light powder, borneol, and lithospermum officinale, pass through a 60-80 mesh sieve, mix evenly, add 3-5 times the amount of distilled water and boil for 2-3 times, filter while hot, combine the filtrate, and then concentrate to 1 / 5 to 1 / 3 of the original volume of the filtrate, dry, and crush to obtain a Chinese medicine extract; (2) adding 80-100 mg of the Chinese herbal extract described in step S1, 180-200 mg of soybean lecithin, and 30-40 mg of cholesterol to 20-30 mL of an ethanol solution with a mass fraction of 80%, stirring at a constant temperature, slowly injecting into the aqueous phase, hydrating at a constant temperature, evaporating clean ethanol, ultrasonically crushing, and filtering through a 0.22 μm water membrane to obtain Chinese herbal liposomes; (3) Add chitosan to 20 mL of isopropanol solution and react for 3-4 h, then add 25 mL of 30% sodium hydroxide solution and set aside, weigh 3.0 g of chloroacetic acid and dissolve it in 20 mL of isopropanol solution, slowly pour it into the chitosan solution under stirring conditions using a magnetic stirrer, fully react for 1-2 h, let stand for stratification, remove the upper layer solution, take 50 mL of distilled water and add it, stir magnetically for 5 min, adjust the pH to 7.0 with 10% hydrochloric acid solution, centrifuge once, fully precipitate the supernatant with methanol, centrifuge twice, then add anhydrous ethanol to wash the precipitate, centrifuge three times to obtain a carboxymethyl chitosan solution; (4) Slowly adding the Chinese medicine liposomes described in step (2) into the carboxymethyl chitosan solution described in step (3), placing the mixed solution in a magnetic stirrer, controlling the temperature at 40-50°C, the rotation speed at 10-20 rpm, stirring for 0.5-1 h, and then subjecting the mixture to intermittent ultrasonic treatment for 10-20 min to obtain carboxymethyl chitosan-modified Chinese medicine liposomes.

6. The method for preparing the Chinese medicine composition for treating hemorrhoids according to claim 5, characterized in that: In step (3), the amount of chitosan added is 0.5-0.6 g.

7. The method for preparing the Chinese medicine composition for treating hemorrhoids according to claim 6, characterized in that: In step (4), during the intermittent ultrasonic treatment, the ultrasonic treatment was performed for 2 minutes and then stopped for 2 minutes.

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