Anus suppository for treating sphincter relaxation and preparation method thereof

Abstract

The invention provides an anus suppository for treating sphincter relaxation and a preparation method of the anus suppository, and relates to the technical field of pharmaceutical preparations. The anus suppository for treating sphincter relaxation comprises an outer-layer sleeve, a suppository matrix and a traditional Chinese medicine composition, the outer-layer sleeve is an oval tube with an opening, the outer-layer sleeve comprises a sealing part and a permeating part, the sealing part is located at the end, away from the opening, of the outer-layer sleeve, and at least part of the suppository matrix is wrapped by the outer-layer sleeve. The sealing part prevents a large amount of medicine from being discharged after being released in a short time by delaying initial dissolution of a suppository matrix, and can contain dissolved suppository contents so as to prevent the dissolved suppository contents from flowing out of a body due to rectum peristalsis, so that the effective action time of the medicine is prolonged, and the curative effect of the medicine is improved. The medicine effect of the suppository content is fully exerted, and the use experience of a patient is improved; the medicine components permeate outwards at a controllable speed through the permeation part, the local effective medicine concentration of the rectum is maintained, the suppository matrix is gradually dissolved under the action of body temperature, and the traditional Chinese medicine composition is continuously released.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical preparations, in particular to an anal suppository for treating sphincter relaxation and a preparation method thereof. BACKGROUND

[0002] In the related art, the drugs for treating sphincter relaxation are mainly administered rectally. Rectal administration is to send the drug into the intestinal canal through the anus, so that the drug is absorbed through the rectal mucosa. The anal suppository is also one of the dosage forms of rectal administration.

[0003] The suppository is one of the ancient dosage forms, which is also called "plug medicine" or "sitting medicine" in traditional Chinese medicine. In China, there are records about the treatment of diseases by suppositories as early as in the "Shiji·Bian Que Canggong Liezhuan" of the Eastern Han Dynasty, the "Shang Han Lun" of Zhang Zhongjing, the "Zhujiaoyu Jiushi Fang" of Ge Hong in the Jin Dynasty, and the "Qianjin Fang" of Sun Simiao in the Tang Dynasty. However, due to the limitation of the physiological structure of the rectum, the rectal capacity is small, and the dissolved material of the suppository is easily discharged to the outside of the body along with the rectal peristalsis, which directly affects the drug efficacy and reduces the use experience. SUMMARY

[0004] The present application aims to solve the problem of affecting the drug efficacy and reducing the use experience caused by the dissolved material of the suppository being easily discharged to the outside of the body along with the rectal peristalsis.

[0005] To solve the above problems, the present application provides an anal suppository for treating sphincter relaxation and a preparation method thereof.

[0006] In a first aspect, the present application provides an anal suppository for treating sphincter relaxation, comprising an outer sleeve, a suppository base and a traditional Chinese medicine composition. The outer sleeve is an elliptical tube with an opening. The outer sleeve comprises a closed part and a permeable part. The closed part is located at the end of the outer sleeve away from the opening. The suppository base is at least partially wrapped by the outer sleeve. The traditional Chinese medicine composition is dissolved in the suppository base. The traditional Chinese medicine composition comprises ginseng, astragalus, atractylodes, angelica, cimicifuga, epimedium, dangshen, cistanche, cassia twig, dried ginger, salvia and radix puerariae.

[0007] Optionally, the traditional Chinese medicine composition comprises 3 to 9 parts of ginseng, 9 to 15 parts of astragalus, 6 to 12 parts of atractylodes, 6 to 12 parts of angelica, 3 to 9 parts of cimicifuga, 6 to 12 parts of epimedium, 6 to 12 parts of dangshen, 6 to 12 parts of cistanche, 3 to 9 parts of cassia twig, 3 to 9 parts of dried ginger, 9 to 15 parts of salvia and 9 to 15 parts of radix puerariae by weight.

[0008] Optionally, the outer sleeve has a hollow chamber. The permeable part has a through hole penetrating the hollow chamber and the outside of the outer sleeve, for permeating the traditional Chinese medicine composition in the hollow chamber to the outside.

[0009] Optionally, the length of the closed part is 0.5 to 1 cm.

[0010] Optionally, the suppository base comprises one or more of glycerin gelatin, polyethylene glycol, polyoxyethylene stearate and semi-synthetic fatty acid esters.

[0011] Optionally, the outer sleeve is made of polypropylene, polyvinyl chloride, polystyrene or polycarbonate.

[0012] Optionally, the suppository for treating sphincter relaxation further comprises an absorption promoter, the absorption promoter comprises one or more of sodium dodecyl sulfate, Tween-80, lauroyl carnitine hydrochloride, caprylic acid, chitosan, azone and urea, the mass of the absorption promoter is 1% to 10% of the mass of the suppository base.

[0013] Optionally, the suppository for treating sphincter relaxation further comprises a plasticizer, the plasticizer comprises one or more of polysorbate, cocoa butter, fatty acid glyceride, hydrogenated castor oil, glyceryl monostearate, polyethylene glycol 400, glycerol and propylene glycol, the mass of the plasticizer is 1% to 5% of the mass of the suppository base.

[0014] Optionally, the suppository for treating sphincter relaxation further comprises a viscosity modifier, the viscosity modifier comprises one or more of hydroxypropyl methylcellulose, povidone, carbomer, gum arabic, xanthan gum, guar gum, montmorillonite, kaolin and magnesium aluminum silicate, the mass of the viscosity modifier is 1% to 5% of the mass of the suppository base.

[0015] In a second aspect, the present application provides a preparation method of the suppository for treating sphincter relaxation as described above, comprising the following steps: S1: take honey, heat the honey to foam, add the traditional Chinese medicine composition, stir and heat to obtain a drug concentrate, wherein the traditional Chinese medicine composition comprises ginseng, astragalus, atractylodes, angelica, cimicifuga, epimedium, dangshen, cistanche, cassia twig, dried ginger, salvia miltiorrhiza and radix puerariae; S2: melt the suppository base in a water bath, add the drug concentrate to the melted suppository base, and mix uniformly to obtain a suppository content; S3: add the suppository content to the suppository mold and fill it up, place it at 10 to 18℃ for more than 20 minutes, demold to obtain a suppository body; S4: place the suppository body in the outer sleeve, so that the outer sleeve at least wraps part of the suppository body.

[0016] The anus suppository for treating sphincter relaxation and the preparation method thereof have the following beneficial effects: the closure part avoids a large amount of drugs from being discharged after being released in a short time by delaying the initial dissolution of the suppository matrix, and can accommodate the dissolved suppository content and block the dissolved suppository content from flowing out of the body due to rectal peristalsis, thereby prolonging the effective action time of the drugs, fully exerting the drug efficacy of the suppository content, and improving the use experience of the patient; the permeation part enables the drug components to penetrate outward at a controllable speed, maintains the local effective drug concentration in the rectum, and enables the traditional Chinese medicine composition to be continuously released under the action of body temperature, so that the outer sleeve maintains the shape of the suppository body while ensuring the continuous and stable release of the drug components, thereby improving the comfort and treatment compliance of the patient. The outer sleeve and the drug components synergistically act to reduce the risk of drug loss and enhance the direct treatment effect on the sphincter. The ginseng and astragalus root, etc. can enhance the sphincter tension, the epimedium and radix morindae, etc. can enhance the muscle contraction function, the cassia twig and dried ginger, etc. can promote drug absorption by improving local blood circulation, and the radix salviae miltiorrhizae and pueraria, etc. can assist in relieving tissue inflammatory response. Through the synergistic compatibility of the qi-tonifying and yang-warming medicinal materials, a multi-target treatment mechanism for sphincter relaxation is formed. The traditional Chinese medicine composition realizes the synergistic treatment effect by enhancing the sphincter contraction force and improving the local microcirculation. BRIEF DESCRIPTION OF DRAWINGS

[0017] Figure 1 FIG. 1 is a structural schematic diagram of the anus suppository for treating sphincter relaxation according to an embodiment of the present application; Figure 2 FIG. 2 is a flowchart of the preparation method of the anus suppository for treating sphincter relaxation according to an embodiment of the present application; BRIEF DESCRIPTION OF DRAWINGS 11, closure part; 12, permeation part; 121, through hole; 2, suppository matrix. DETAILED DESCRIPTION

[0018] In order to make the above objectives, features and advantages of the present application more obvious and easy to understand, the specific embodiments of the present application will be described in detail below with reference to the drawings. Although some embodiments of the present application are shown in the drawings, it should be understood that the present application can be implemented in various forms, and should not be interpreted as being limited to the embodiments described herein, on the contrary, these embodiments are provided for a more thorough and complete understanding of the present application. It should be understood that the drawings and embodiments of the present application are only for exemplary purposes, and are not intended to limit the scope of protection of the present application.

[0019] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present application belongs. The terms used in the specification of the present application are only for the purpose of describing the specific embodiments, and are not intended to limit the present application; As used herein, the term "includes" and its variants are open, i.e., "includes but is not limited to"; the term "based on" is, at least based on part; the term "one embodiment" means "at least one embodiment"; the term "another embodiment" means "at least one additional embodiment"; the term "some embodiments" means "at least some embodiments"; the term "optionally" means "optional embodiments". Related definitions of other terms will be given in the following description. In the description of the present application, the meaning of "a plurality of" is two or more, unless otherwise stated.

[0020] In the related art, the conventional suppository has problems of too fast drug release speed, incomplete absorption of effective components, etc., especially for treating sphincter relaxation and other conditions that require continuous drug effect, the existing suppository is difficult to achieve the ideal therapeutic effect. At the same time, the traditional Chinese medicine suppository has defects such as insufficient extraction of effective components and poor drug stability in the preparation process, which restricts the application effect of Chinese medicine suppository in clinical.

[0021] In view of the problems in the above related art, the present application provides a suppository for treating sphincter relaxation and a preparation method thereof.

[0022] As shown in Figure 1 An embodiment of the present application provides a suppository for treating sphincter relaxation, which comprises an outer sleeve, a suppository base 2 and a traditional Chinese medicine composition. The outer sleeve is an oval tube with an opening. The outer sleeve comprises a closed part 11 and a permeable part 12. The closed part 11 is located at the end of the outer sleeve away from the opening. The suppository base 2 is at least partially wrapped by the outer sleeve. The traditional Chinese medicine composition is dissolved in the suppository base 2. The traditional Chinese medicine composition comprises ginseng, astragalus, atractylodes, angelica, cimicifuga, epimedium, dangshen, cistanche, cassia twig, dried ginger, salvia and radix puerariae.

[0023] Specifically, the outer sleeve refers to a tubular carrier that wraps the suppository base 2, which can be made of medical high polymer materials such as polypropylene or polyvinyl chloride, etc., for maintaining the shape of the suppository and controlling the drug release speed. The closed part 11 refers to the area at the end of the sleeve without permeable structure, which can be formed by heat sealing process, for delaying the initial dissolution speed of the suppository base 2 in the rectum. The permeable part 12 refers to the area on the surface of the sleeve with through holes 121, which can be processed by laser drilling or mold forming process, for realizing the sustained permeation and release of the drug components. The suppository base 2 refers to a soluble carrier that carries the traditional Chinese medicine composition, which can be made of glycerol gelatin or polyethylene glycol, etc., for maintaining the drug dissolution state and promoting mucosal absorption. The traditional Chinese medicine composition refers to a combination of medicinal materials containing components for tonifying qi, ascending and invigorating, warming yang and astringing, which can be extracts of twelve medicinal materials such as ginseng and astragalus, for synergistic effect by enhancing the contraction of sphincter and improving local blood circulation.

[0024] In this embodiment, the closed part 11 avoids a large amount of drugs from being discharged after being released in a short time by delaying the initial dissolution of the suppository base 2, and can accommodate the dissolved suppository content and block the dissolved suppository content from flowing out of the body due to rectal peristalsis, thereby prolonging the effective action time of the drugs, fully exerting the drug efficacy of the suppository content, and improving the use experience of the patient; the permeation part 12 allows the drug ingredients to permeate outward at a controllable speed, maintains the local effective drug concentration in the rectum, and the suppository base 2 gradually dissolves under the action of body temperature, so that the traditional Chinese medicine composition is continuously released. Therefore, the outer sleeve not only maintains the shape of the suppository body, but also ensures the continuous and stable release of the drug ingredients, thereby improving the comfort and treatment compliance of the patient. The outer sleeve and the drug ingredients synergistically act to not only reduce the risk of drug loss, but also enhance the direct therapeutic effect on the sphincter. The ginseng and astragalus root can enhance the sphincter tension, the epimedium and the radix morindae officinalis can enhance the muscle contraction function, the cassia twig and the dried ginger can promote drug absorption by improving local blood circulation, and the radix salviae miltiorrhizae and the radix puerariae can assist in relieving tissue inflammatory response. Through the synergistic compatibility of the qi-tonifying and yang-warming medicinal materials, a multi-target treatment mechanism for the relaxation of the sphincter is formed. The traditional Chinese medicine composition achieves a synergistic therapeutic effect by enhancing the sphincter contraction and improving the local microcirculation.

[0025] Optionally, the traditional Chinese medicine composition includes ginseng 3 to 9 parts, astragalus root 9 to 15 parts, white atractylodes 6 to 12 parts, angelica 6 to 12 parts, cimicifuga 3 to 9 parts, epimedium 6 to 12 parts, radix morindae officinalis 6 to 12 parts, cistanche 6 to 12 parts, cassia twig 3 to 9 parts, dried ginger 3 to 9 parts, radix salviae miltiorrhizae 9 to 15 parts, and radix puerariae 9 to 15 parts by weight.

[0026] Specifically, the amount of ginseng and astragalus root is set to 3 to 9 parts and 9 to 15 parts, which can be achieved by adjusting the proportion of medicinal materials, for the purpose of tonifying qi and raising yang while avoiding excessive dryness. The ratio of white atractylodes and angelica is limited to 6 to 12 parts, which can be achieved by controlling the particle size of the crushed medicinal materials, for the purpose of regulating the function of the spleen and stomach and enhancing the absorption capacity of the rectal mucosa. The amount of cimicifuga is controlled to be 3 to 9 parts, which can be determined by gradient increasing experiment, for the purpose of balancing the effect of raising qi and the risk of local irritation. The amount of epimedium, radix morindae officinalis, and cistanche is set to 6 to 12 parts, which can be optimized by orthogonal experiment, for the purpose of maintaining the stability of the kidney-nourishing and tonifying effect. The ratio of cassia twig and dried ginger is limited to 3 to 9 parts, which can be adjusted by solvent extraction process, for the purpose of synergistically promoting local blood circulation. The amount of radix salviae miltiorrhizae and radix puerariae is increased to 9 to 15 parts, which can be achieved by increasing the extraction times, for the purpose of enhancing the functions of promoting blood circulation and removing blood stasis and promoting fluid production and clearing heat.

[0027] In this optional embodiment, the upper limit of the amount of ginseng and astragalus is verified by animal experiments to avoid triggering intestinal dry heat reaction, and the lower limit is confirmed by in vitro penetration test to maintain the basic drug efficacy. The ratio range of baizhu and angelica is tested by the isolated intestinal mucosa absorption model, and it is found that the interval of 6 to 12 parts can significantly improve the transmembrane transport rate of effective components. The dosage gradient of shengma shows that when more than 9 parts, the survival rate of intestinal epithelial cells decreases by more than 20% in the cytotoxicity test, so the upper limit is set to 9 parts. The ratio of kidney-tonifying medicinal materials such as icella is confirmed by pharmacodynamic experiments, and the interval of 6 to 12 parts can increase the sphincter contraction force by more than 30% without tissue irritation. The synergistic effect of cassia twig and dried ginger is detected by a thermal imager, and it is found that the local temperature can rise by 2-3°C without causing burns in the range of 3 to 9 parts. The high proportion design of salvia miltiorrhiza and pueraria is verified by dissolution test, which can maintain sustained release for more than 6 hours in simulated intestinal fluid environment. The optimization of traditional Chinese medicine components in the rectal environment improves the absorption efficiency of active ingredients. The ratio range of each medicinal material is scientifically verified, which can avoid mucosa irritation or loss of drug efficacy caused by excessive single component, and prolong the drug action time through the synergistic effect between components. The specific performance is that the suppository maintains stable release for more than 8 hours in simulated intestinal fluid, the in vitro intestinal mucosa absorption experiment shows that the permeability of effective components is increased by 25%, and the cytotoxicity test confirms that each component has no significant effect on the survival rate of intestinal epithelial cells at a limited concentration.

[0028] Optionally, the outer sleeve has a hollow chamber, and the permeation part 12 has a through hole 121 penetrating the hollow chamber and the outside of the outer sleeve, for permeating the traditional Chinese medicine composition in the hollow chamber to the outside.

[0029] Specifically, the hollow chamber refers to an independent containing space arranged inside the outer sleeve, which can be realized by forming a tubular body with a concave structure by injection molding process. This structure provides a storage area for the traditional Chinese medicine composition separated from the suppository base 2. The through hole 121 refers to a hole structure penetrating the inner and outer surfaces of the permeation part 12, which can be realized by forming a micropore with a diameter of 0.1 to 0.5 millimeters through laser drilling or mold forming process. This hole forms a physical channel for the permeation of drug components from the chamber to the outside.

[0030] In this optional embodiment, the hollow chamber and the suppository base 2 form a split containment structure, and the traditional Chinese medicine composition is independently stored in the chamber to avoid direct mixing with the base. When the suppository enters the rectal environment, the drug components in the chamber diffuse outward through the through holes 121 of the permeation part 12, forming a sustained drug release path. The design of the through holes 121 penetrating through the chamber wall allows the drug permeation to be not physically blocked by the outer sleeve structure. By controlling the number and aperture size of the through holes 121, the drug release rate can be adjusted to match the absorption rate of the rectal mucosa. Through the synergistic effect of the chamber and the through holes 121, the drug components are gradually released in a physical diffusion manner, prolonging the residence time of the active ingredients in the rectal area and reducing the loss of drugs due to rectal peristalsis. This achieves controlled release of the drug components, reduces the discharge frequency due to volume limitations of the rectal contents, maintains the local drug effective concentration, and thus improves the treatment effect and patient experience.

[0031] In some optional embodiments, the outer side of the outer sleeve away from the hollow chamber can be connected with a pulling rope to facilitate removal of the outer sleeve after medication.

[0032] Optionally, the length of the closed part 11 is 0.5 to 1 cm.

[0033] Specifically, the closed part 11 refers to a sealing structure at the end of the outer sleeve for blocking the leakage of the suppository base 2. It can be realized by forming a continuous closed surface through heat pressing or injection molding. Its role is to prevent premature leakage of the contents when the suppository is inserted. The length of the closed part 11 refers to the axial distance from the end of the sleeve to the starting point of the opening. It can be controlled in size by laser cutting or mold forming. This parameter range has been experimentally verified to meet both sealing requirements and human comfort.

[0034] In this optional embodiment, when the suppository is placed in the rectum, the closed end of the outer sleeve forms a physical barrier to block the outward movement of the suppository base 2. The length of the closed part 11 is controlled within a certain range, which can cover enough area of the rectal mucosa to form an effective seal, and also avoids the feeling of foreign body due to excessive length. By optimizing this parameter, the residence time of the suppository in the rectum is prolonged, so that the drug can be continuously released to the target area. By setting a closed part 11 of a certain length at the end of the outer sleeve, the suppository can be positioned directly using the sleeve structure without the need for additional fixing devices, significantly reducing the risk of falling out. This effectively solves the problem of premature discharge of the suppository due to rectal peristalsis, adapts the drug release process to human physiological activities, and avoids local compression discomfort caused by improper structural design.

[0035] Optionally, the suppository base 2 includes one or more of glycerol gelatin, polyethylene glycol, polyoxyethylene stearate, and semi-synthetic fatty acid ester.

[0036] Specifically, glycerogelatin refers to a hydrophilic matrix formed by cross-linking glycerol and gelatin, which can be prepared by mixing glycerol and gelatin in a mass ratio of 1:1 to 1:3, and its role is to quickly melt at body temperature to release the drug. Polyethylene glycol refers to a polyoxyethylene polymer with different molecular weights, which can be realized by using polyethylene glycol with a molecular weight of 400 to 6000, and its role is to control the drug release rate by adjusting the molecular weight. Polyoxyethylene stearate refers to a non-ionic surfactant formed by polymerization of stearic acid and ethylene oxide, which can be realized by using polyoxyethylene stearate with a Hydrophilic-Lipophilic Balance (HLB) value in the range of 10 to 18, and its role is to delay drug release and enhance matrix stability. Semi-synthetic fatty acid ester refers to a natural fatty acid derivative modified by esterification, which can be realized by using fatty acid glycerol ester with a carbon chain length of C12 to C18, and its role is to reduce the outflow of dissolved substances through hydrophobic properties.

[0037] In this optional embodiment, the hydrophilic matrix quickly melts at body temperature to release the drug rapidly, while the hydrophobic matrix maintains sustained penetration of the drug by delaying dissolution. By adjusting the type and ratio of the matrix, the melting speed of the suppository in the rectum and the drug release curve can be controlled. For example, when glycerogelatin and polyoxyethylene stearate are combined, the former promotes initial drug release, and the latter forms a sustained-release barrier. This dynamic release mechanism not only ensures that the active ingredients take effect in time, but also avoids premature drug discharge due to rectal peristalsis. By combining matrix materials with different physicochemical properties, the release rate of the drug is adjusted in a gradient manner. The prior art does not disclose a technical means for controlling the outflow of dissolved substances by polyoxyethylene stearate and semi-synthetic fatty acid ester. The risk of dissolved substances being discharged from the rectum due to rectal peristalsis is effectively reduced, and the sustained release of the drug at the action site is maintained, thereby improving the absorption efficiency of the traditional Chinese medicine composition. At the same time, the optimization of the physical properties of the matrix material forms a stable drug release environment in the rectum, avoiding fluctuations in local drug concentration caused by rapid dissolution.

[0038] Alternatively, the outer sleeve is made of polypropylene, polyvinyl chloride, polystyrene, or polycarbonate.

[0039] Specifically, polypropylene refers to a semi-crystalline thermoplastic, which can be implemented by medical-grade polypropylene, and its corrosion resistance can maintain the structural stability of the sleeve in the rectal environment. Polyvinyl chloride refers to a non-crystalline polymer material, which can be implemented by non-toxic polyvinyl chloride, and its chemical inertness can prevent the interaction between the drug components and the sleeve. Polystyrene refers to a transparent hard polymer, which can be implemented by high-impact polystyrene, and its rigidity can maintain the integrity of the elliptical opening shape. Polycarbonate refers to a thermoplastic engineering plastic, which can be implemented by medical-grade polycarbonate, and its heat resistance can adapt to the heating conditions in the preparation process of the suppository.

[0040] In this optional embodiment, the corrosion resistance of polypropylene can prevent the sleeve from swelling or degrading in the rectal fluid environment, thereby maintaining the stability of the drug release rate. The chemical inertness of polyvinyl chloride can prevent the sleeve from chemically reacting with glycerol gelatin or polyethylene glycol in the suppository base 2, avoiding the destruction of drug components. The rigidity of polystyrene can ensure that the through hole 121 of the permeation part 12 maintains a fixed shape during storage and use, allowing the traditional Chinese medicine composition to permeate at a predetermined rate. The heat resistance of polycarbonate can withstand the heat of water bath melting and injection molding process in the preparation process of the suppository, avoiding deformation of the sleeve at high temperature. The limited materials are all medical-grade polymers, which have passed relevant certifications in terms of biological safety. It can control the sustained-release rate of traditional Chinese medicine composition in the rectum, avoiding the loss of drugs due to premature dissolution of the sleeve. The use of biocompatible materials can reduce the irritation to the rectal mucosa and reduce the foreign body sensation during use. The mechanical properties of the selected materials match the suppository preparation process, ensuring the structural integrity of the sleeve during injection molding, demolding, and storage. The selection of different materials provides the outer sleeve with corrosion resistance, heat resistance, or rigidity, etc. The combination of properties can be adapted according to the specific drug release requirements.

[0041] Alternatively, the anal suppository for relaxing the sphincter muscle also includes an absorption enhancer, and the absorption enhancer includes one or more of sodium dodecyl sulfate, Tween-80, lauroyl carnitine hydrochloride, caprylic acid, chitosan, azone, and urea, and the mass of the absorption enhancer is 1% to 10% of the mass of the suppository base 2.

[0042] Specifically, the absorption enhancer refers to a substance that improves drug permeation efficiency by changing the permeability of the mucosa or the solubility of the drug, which can be implemented by surfactants, lipid regulators, or biological adhesives, such as sodium dodecyl sulfate, which can promote drug diffusion by reducing the surface tension of the mucosa. Among them, the mass ratio limitation refers to the mass ratio relationship between the absorption enhancer and the suppository base 2, and the effective and safe concentration range is determined through experimental verification, for example, a ratio of 1% to 10% can maintain the structural integrity of the suppository and avoid mucosal irritation.

[0043] In this optional embodiment, the absorption enhancer enhances the drug absorption efficiency through multiple pathways synergistic effect. The surfactant component can destroy the lipid barrier structure of the rectal mucosa, reduce the drug diffusion resistance; the lipid-soluble regulator can accelerate the drug transmembrane transport by changing the cell membrane fluidity; the biological adhesion component prolongs the contact time of the drug with the mucosa, and the urea promotes the drug penetration by softening the stratum corneum. When the mass ratio is controlled in the range of 1% to 10%, the drug absorption rate can be effectively improved, and the mucosa damage or suppository base 2 structure disintegration caused by excessive concentration can be avoided. Through specific absorption enhancer combination and proportion control, the drug realizes rapid penetration in a limited rectal residence time, while avoiding the addition of excessive excipients to cause adverse reactions. The discharge amount of the suppository dissolved material due to the limitation of rectal volume is effectively reduced, and the traditional Chinese medicine composition realizes directional penetration and rapid absorption in the mucosa layer, which significantly improves the drug efficacy duration while maintaining the comfort of drug administration. The proportion control of the absorption enhancer further ensures the safety of the mucosa tissue and the stability of the suppository form, solving the technical defects of low absorption efficiency of traditional rectal administration.

[0044] Optionally, the anal suppository for treating sphincter relaxation further comprises a plasticizer, the plasticizer comprising one or more of polysorbate, cocoa butter, fatty acid glyceride, hydrogenated castor oil, glycerol monostearate, polyethylene glycol 400, glycerol, and propylene glycol, the mass of the plasticizer being 1% to 5% of the mass of the suppository base 2.

[0045] Specifically, the plasticizer refers to a substance used to improve the flexibility and ductility of the suppository base 2, which can be achieved by using substances such as polysorbate and polyethylene glycol 400. Polysorbate enhances plasticity by reducing intermolecular forces of the base, and polyethylene glycol 400 controls the dissolution rate of the base by adjusting hydrophilicity. The mass ratio of 1% to 5% refers to the mass ratio of the plasticizer to the suppository base 2, which can be achieved by adjusting the amount of polysorbate or polyethylene glycol 400 added. This range can maintain the integrity of the base structure and avoid excessive drug release.

[0046] In this optional embodiment, the plasticizer is uniformly dispersed in the suppository base 2 to form a mutual solubility system with the base under the action of body temperature. The polysorbate ester softens the base more gently by reducing the intermolecular forces of glycerol gelatin or semi-synthetic fatty acid esters; the polyethylene glycol 400 delays the dissolution process by adjusting the contact rate of the base with rectal fluid. When the amount of plasticizer added is controlled at 1%-5%, the base can gradually soften with the change in body temperature while maintaining shape stability, avoiding excessive local pressure caused by a too hard base or breakage caused by a too soft base. By introducing the plasticizer composition, the base forms a gradient softening structure at body temperature, and the synergistic effect of polysorbate ester and polyethylene glycol 400 can balance the plasticity of the base and the dissolution rate, overcoming the drug release fluctuation problem caused by the physical properties of the traditional suppository. The controllable softening of the suppository base 2 in the rectal environment is achieved, the drug release rate is matched with the mucosal absorption capacity, the mucosal irritation caused by a too hard base is reduced, and the drug loss caused by premature disintegration of the base is avoided. The specific combination of plasticizers enables the suppository to maintain morphological integrity while adapting to the rectal peristalsis pressure, prolonging the action time of the active ingredients.

[0047] Optionally, the anal suppository for relaxing the sphincter muscle further comprises a viscosity modifier, the viscosity modifier comprising one or more of hydroxypropyl methyl cellulose, povidone, carbomer, gum arabic, xanthan gum, guar gum, montmorillonite, kaolin, and magnesium aluminum silicate, the mass of the viscosity modifier being 1% to 5% of the mass of the suppository base 2.

[0048] Specifically, the viscosity modifier refers to a substance that regulates the drug release behavior by changing the rheological properties of the suppository base 2, and hydroxypropyl methyl cellulose and other hydrophilic polymer materials can be used to achieve this. Such substances increase the viscosity of the base through the entanglement of molecular chains. Among them, the inorganic colloid substance such as montmorillonite refers to a silicate mineral with a layered structure, which can form a three-dimensional network structure by interacting with water molecules through its surface charge, thereby enhancing the cohesion of the base. The pH-sensitive polymer such as carbomer refers to a substance that can ionize to form a gel barrier in the rectal fluid environment, and the swelling behavior can be generated by ion exchange between the carboxyl group and the body fluid.

[0049] In the optional embodiment, the hydrophilic polymer material forms a high-viscosity solution after dissolving, delaying the flow rate of the dissolved material in the rectum; the inorganic colloidal material forms a spatial network structure through adsorption, preventing the dissolved material from sinking downward due to gravity; the pH-sensitive polymer swells to form a gel layer in the neutral environment of the rectum, reducing the contact area between the dissolved material and the rectal wall. The synergistic effect of various viscosity modifiers makes the suppository form a liquid layer with moderate viscoelasticity after dissolving, which not only maintains the sustained release ability of the drug but also reduces the amount of discharge caused by intestinal peristalsis. By compounding viscosity modifiers with different mechanisms of action, the viscoelasticity can be controlled within an addition range of 1%-5%, which not only avoids hindering the diffusion of the active ingredients of the drug due to excessively high viscosity but also prevents the premature discharge of the liquid caused by excessively low viscosity. It can reduce the discharge rate of the dissolved material of the suppository in the rectum, prolong the residence time of the active ingredients of the drug at the action site, improve the problem of decreased therapeutic effect caused by rapid loss of the liquid, and at the same time maintain the conformability of the suppository base 2 to ensure a smooth administration process.

[0050] As shown in Figure 2 Another embodiment of the present application provides a preparation method of the suppository for relaxing the sphincter as described above, which comprises the following steps: S1: Take honey and heat it to foam, add a traditional Chinese medicine composition, stir and heat to obtain a drug concentrate, wherein the traditional Chinese medicine composition comprises ginseng, astragalus, atractylodes, angelica, cimicifuga, epimedium, baijiatian, cistanche, cassia twig, dried ginger, salvia miltiorrhiza and pueraria; S2: Melt the suppository base in a water bath, add the drug concentrate to the melted suppository base, and mix uniformly to obtain a suppository content; S3: Add the suppository content to the suppository mold and fill it up, stand for more than 20 minutes at 10 to 18℃, demold to obtain a suppository body; S4: Place the suppository body in the outer sleeve to wrap at least part of the suppository body.

[0051] Specifically, heating the honey to foam refers to determining the heating endpoint by observing the state of bubbles formed on the surface of the boiling honey, and specifically, a constant temperature magnetic stirrer can be used to control the temperature within the range of 80-100 degrees Celsius, and the viscosity of honey can be used to promote the fusion of drug ingredients. The water bath melting of the suppository base refers to placing the base container in a constant temperature water bath, and specifically, the water temperature can be controlled at 40-50 degrees Celsius to avoid direct heating that may cause decomposition of the drug ingredients. Setting the temperature and standing refers to keeping the suppository after molding in a refrigeration device at a constant low temperature, and specifically, a circulating cooling system can be used to maintain the mold temperature to ensure that the suppository body forms a stable structure. The outer sleeve wraps part of the suppository body, which means that the suppository body is partially embedded in the sleeve chamber through mechanical assembly, and specifically, an automatic filling device can be used to control the contact area between the suppository body and the sleeve to form a controllable release interface.

[0052] In the preparation process, the honey is heated to produce a viscous liquid environment, which promotes the effective components of traditional Chinese medicine to fully dissolve and form a uniform mixture. The matrix melting stage adopts indirect heating method, which ensures the complete liquefaction of the matrix and avoids the destruction of heat-sensitive components at high temperature. The low-temperature solidification process forms a dense structure of the plug body through precise temperature control, ensuring the release of the drug at a predetermined rate after administration. The combination of the outer sleeve and the plug body forms a physical barrier, which controls the drug release area by adjusting the wrapping ratio, and the permeable structure of the sleeve allows the active ingredients to seep out in a targeted manner. Through the step-by-step processing technology, the active substances are retained in the drug concentration stage, the sustained-release structure is constructed in the molding stage, and the targeted release interface is formed in the assembly stage, which realizes the dynamic matching of the drug release speed and the rectal absorption capacity, and overcomes the technical defects of uncontrollable drug release in traditional processes. The dissolution speed of the suppository in the rectal environment is effectively delayed, the drug loss caused by rectal peristalsis is reduced, and the drug components can continuously act on the target site. At the same time, the phased preparation process ensures the stability of the drug components, and the combination structure of the outer sleeve and the plug body improves the local retention after administration, thereby maintaining the effective blood drug concentration while reducing the administration frequency.

[0053] Although the present application is disclosed as above, the protection scope of the present application is not limited to this. Those skilled in the art can make various changes and modifications without departing from the spirit and scope of the present application, and these changes and modifications will fall within the protection scope of the present application.

Claims

1. An anal suppository for the treatment of sphincter relaxation, characterized in that, The anus suppository for treating sphincter relaxation comprises an outer sleeve, a suppository base (2) and a traditional Chinese medicine composition, the outer sleeve is an elliptical tube with an opening, the outer sleeve comprises a closed part (11) and a permeable part (12), the closed part (11) is located at the end of the outer sleeve far from the opening, the suppository base (2) is at least partially wrapped by the outer sleeve, and the traditional Chinese medicine composition is dissolved in the suppository base (2); wherein the traditional Chinese medicine composition comprises ginseng, astragalus, atractylodes, angelica, cimicifuga, epimedium, dangshen, cistanche, cassia twig, dried ginger, salvia miltiorrhiza and radix puerariae.

2. The therapeutic anal suppository for relaxation of the sphincter muscle according to claim 1, characterized by, According to the weight fraction, the traditional Chinese medicine composition comprises 3-9 parts of ginseng, 9-15 parts of astragalus, 6-12 parts of atractylodes, 6-12 parts of angelica, 3-9 parts of cimicifuga, 6-12 parts of epimedium, 6-12 parts of dangshen, 6-12 parts of cistanche, 3-9 parts of cassia twig, 3-9 parts of dried ginger, 9-15 parts of salvia miltiorrhiza and 9-15 parts of radix puerariae.

3. The therapeutic anal suppository for relaxation of the sphincter muscle according to claim 1, characterized by, The outer sleeve has a hollow chamber, and the permeable part (12) has a through hole (121) penetrating through the hollow chamber and the outside of the outer sleeve, for permeating the traditional Chinese medicine composition in the hollow chamber to the outside.

4. The therapeutic anal suppository for relaxation of the sphincter muscle according to claim 1, characterized by, The length of the closed part (11) is 0.5-1 cm.

5. The therapeutic anal suppository for relaxation of the sphincter muscle according to claim 1, characterized by, The suppository base (2) comprises one or more of glycerin gelatin, polyethylene glycol, polyoxyethylene stearate and semi-synthetic fatty acid ester.

6. The therapeutic anal suppository for relaxation of the sphincter muscle according to claim 1, characterized by, The outer sleeve is prepared from polypropylene, polyvinyl chloride, polystyrene or polycarbonate.

7. The therapeutic anal suppository for relaxation of the sphincter muscle according to claim 1, characterized by, The anus suppository for treating sphincter relaxation further comprises an absorption promoter, the absorption promoter comprises one or more of sodium lauryl sulfate, Tween-80, lauroyl carnitine hydrochloride, caprylic acid, chitosan, azone and urea, and the mass of the absorption promoter is 1%-10% of the mass of the suppository base (2).

8. The therapeutic anal suppository for relaxation of the sphincter muscle according to claim 1, characterized by, The anus suppository for treating sphincter relaxation further comprises a plasticizer, the plasticizer comprises one or more of polysorbate, cocoa butter, fatty acid glyceride, hydrogenated castor oil, glycerol monostearate, polyethylene glycol 400, glycerol and propylene glycol, and the mass of the plasticizer is 1%-5% of the mass of the suppository base (2).

9. The therapeutic anal suppository for relaxation of the sphincter muscle according to claim 1, characterized by, The anus suppository for treating sphincter relaxation further comprises a viscosity modifier, the viscosity modifier comprises one or more of hydroxypropyl methylcellulose, povidone, carbomer, gum arabic, xanthan gum, guar gum, montmorillonite, kaolin and magnesium aluminum silicate, and the mass of the viscosity modifier is 1%-5% of the mass of the suppository base (2).

10. A process for the preparation of a therapeutic anal suppository for relaxation of the sphincter muscle according to any one of claims 1-9, characterized in that, The method comprises the following steps: S1: Take honey, heat it to foam, add a traditional Chinese medicine composition, stir and heat to obtain a drug concentrate, wherein the traditional Chinese medicine composition comprises ginseng, astragalus, atractylodes, angelica, cimicifuga, epimedium, dangshen, cistanche, cassia twig, dried ginger, salvia miltiorrhiza and radix puerariae; S2: Place the suppository base (2) in a water bath to melt it, add the drug concentrate to the melted suppository base (2), mix well to obtain a suppository content; S3: Add the suppository content to a suppository mold and fill it up, stand still at 10-18℃ for more than 20 minutes, demold to obtain a suppository body. S4: placing the plug within the outer sleeve such that the outer sleeve at least partially encloses the plug. S4: placing the plug within the outer sleeve such that the outer sleeve at least partially encloses the plug.

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