Chenopodium ambrosioides and adina pilulifera formula enteric-coated preparation and preparation method thereof

Abstract

The invention relates to a chenopodium ambrosioides and adina pilulifera composition enteric-coated preparation and a preparation method thereof. The enteric-coated preparation is prepared from medicinal components and auxiliary materials of chenopodium ambrosioides and adina pilulifera. Comprising enteric soft capsules and enteric dropping pills. The enteric-coated soft capsule is composed of chenopodium ambrosioides, pilularia adina effective components and a first type of auxiliary materials; the enteric-coated dropping pill is composed of chenopodium ambrosioides, pilularia adina effective components and a second type of auxiliary materials. Medicinal components of the chenopodium ambrosioides and the adina pilulifera are volatile oil of the chenopodium ambrosioides and the adina pilulifera, and the volatile oil is extracted according to the following steps of chopping, soaking, wet crushing, solid-liquid separation, distillation and moisture removal to obtain anhydrous volatile oil; the invention provides a chenopodium ambrosioides and adina pilulifera composition enteric-coated preparation which is not easy to dissolve in the stomach and is dissolved after reaching the intestinal tract for treating intestinal diseases, so that the stimulation of the smell of the medicine to the stomach is avoided. The medicine taking compliance of a patient can be improved. The damage of gastric acid to the medicine is avoided, the concentration of medicinal components in the intestinal tract is improved, and the curative effect on intestinal diseases is enhanced.

Description

Technical Field

[0001] This invention relates to a traditional Chinese medicine preparation, particularly an enteric-coated preparation composed of *Artemisia argyi* and *Hedyotis diffusa*, and its preparation method. Background Technology

[0002] The Chinese medicinal herbs *Euphorbia pekinensis* and *Euphorbia pekinensis* are both traditional Chinese medicines. *Euphorbia pekinensis* was first recorded in *Sheng Cao Yao Xing Bei Yao* and has long been widely used as a folk medicine. The volatile oil of *Euphorbia pekinensis* has significant anti-ulcer and Helicobacter pylori inhibitory effects [Wang Ruiming et al., Study on the effect of Zhonghua Weikang on experimental gastric ulcer and inhibition of HP [J]. Strait Pharmaceutical Journal, 1999(2): 16-19]. Preliminary in vitro antibacterial tests showed that the volatile oil of *Euphorbia pekinensis* has strong inhibitory effects on fungi, Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, and Diplococcus pneumoniae [Pan Xin et al., Gas chromatography-mass spectrometry analysis of volatile oil in *Euphorbia pekinensis* [J]. Journal of Pharmaceutical Analysis, 2007, 27(6): 909-911]. It has different degrees of inhibitory effects on Staphylococcus aureus, Bacillus anthracis, beta-hemolytic streptococcus, and Corynebacterium diphtheriae [Song Kun, Study on chemical composition and bioactivity of *Euphorbia pekinensis* in [D] Peking Union Medical College Graduate School, 2014].

[0003] The main chemical components of the volatile oil of *Gnaphalium affine* are p-cymene, cytotoxicin, borneolene, and α-terpinene. The volatile oil of *Gnaphalium affine* has broad-spectrum antibacterial activity and strong inhibitory and inactivating effects on common pathogens in clinical disinfection [Nie Xiaoni et al., Study on chemical composition and antibacterial activity of volatile oil of *Gnaphalium affine*, Journal of Northwest A&F University (Natural Science Edition), Vol. 38, No. 11, November 2010, pp. 151-154].

[0004] It has the effects of dispelling wind, removing dampness, killing insects, promoting menstruation, and relieving pain. It is used to treat skin rheumatic pain, hookworm, roundworm, dysmenorrhea, amenorrhea, skin eczema and snake and insect bites, etc. [China Pharmaceutical University et al., eds., Chinese Materia Medica Dictionary [M] Volume 1, Beijing: China Medical Science and Technology Press, 1993; 1; 232].

[0005] According to the "Jiangxi Traditional Chinese Medicine", it is "suitable for treating hookworm disease, indigestion, gastrointestinal distension, amenorrhea, and dysmenorrhea". Clinical studies have shown that it can promote ulcer healing and prevent ulcer recurrence [Zhan Chengyue et al. Comparative study of Jinghua Weikang Capsules and Famotidine in the treatment of duodenal ulcers [J]. Zhejiang Journal of Traditional Chinese Medicine, 2005, (5): 223].

[0006] The contents of *Euphorbia hirta*-*Euphorbia humifusa* promote the secretion of protective factors in the gastric mucosa and upregulate the EGFR level of gastric mucosal epithelial cells, thereby promoting ulcer healing [Cao Mingbo et al. Study on the mucosal protective effect of *Euphorbia hirta*-*Euphorbia humifusa* on gastric ulcer rats, Chinese Journal of Traditional Chinese Medicine, Vol. 32, No. 1, January 2007, pp. 49-52].

[0007] Water lily is a plant of the genus Water lily in the Rubiaceae family. It is distributed in Fujian, Jiangxi, Hunan, Zhejiang, Guangxi and Guangdong. Its roots can be used for medicinal purposes and have the effects of clearing heat and dampness, eliminating blood stasis and relieving pain, stopping bleeding and promoting tissue regeneration [Jiangsu New Medical College. Dictionary of Chinese Materia Medica [M]. Shanghai: Shanghai Science and Technology Press, 1995: 527].

[0008] The Fujian Folk Herbal Medicine records its medicinal properties as: bitter, neutral.

[0009] The *Nanning City Materia Medica* records: Astringent, slightly toxic. Functions and indications: Clears heat and promotes diuresis, eliminates blood stasis and relieves pain, stops bleeding and promotes tissue regeneration. Treats dysentery, enteritis, damp-heat edema, carbuncles and boils, eczema, foot ulcers, non-healing ulcers, and traumatic bleeding.

[0010] According to the "Dictionary of Traditional Chinese Medicine," it is sweet and bland, slightly cold in nature. It clears heat and promotes diuresis, eliminates blood stasis and relieves pain, stops bleeding and promotes tissue regeneration. It treats dysentery, enteritis, damp-heat edema, carbuncles and boils, eczema, foot ulcers, non-healing ulcers, and traumatic bleeding.

[0011] According to *Chinese Materia Medica*, it is bitter, astringent, and cool in nature; it enters the liver, spleen, and large intestine meridians; it clears heat and removes dampness; disperses blood stasis and relieves pain; it stops bleeding and promotes wound healing. It is used to treat dysentery; enteritis; edema; carbuncles and boils; eczema; non-healing ulcers; and traumatic bleeding.

[0012] It has the effects of clearing heat and promoting diuresis; detoxifying and reducing swelling. It is mainly used to treat damp-heat diarrhea, dysentery, eczema, boils, carbuncles, toothache due to wind and fire, traumatic injuries, and external bleeding [Editorial Committee of "Chinese Materia Medica" of the State Administration of Traditional Chinese Medicine. Chinese Materia Medica [M] Shanghai: Shanghai Science and Technology Press, 1999].

[0013] It mainly contains chemical components such as alkaloids, chromones, chinocanaic acid and its glycolipids [Xue Junyi et al. Study on chemical components of water lily [J] Chinese Medicinal Herbs, 2007, 30(9): 1084-1086]. Triterpenoids, chromones, alkaloids, and scopolamine were also detected; carotene, loganin, β-sitosterol, aescin, scopolamine, isovanillic acid, caffeic acid [Yuan Ningning et al. Study on chemical components of water lily [J] Journal of Jinan University, 2009, 30(3): 302-304].

[0014] The inhibition rate against bacteria can reach about 80%, and the bactericidal effect against Streptococcus mutans is better. The minimum bactericidal concentration is 0.5% to 2.5% [Wang Yuhua et al. Study on the antibacterial effect of Myrica rubra in the preservation treatment of deep caries [J]. Journal of Stomatology, 1989, 5(4): 206-208].

[0015] It has inhibitory effects on Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Micrococcus luteus or Salmonella choleraesuis to varying degrees. Among them, the steroid mixture has the best antibacterial effect, and the minimum inhibitory concentration (MIC) for Micrococcus luteus and Staphylococcus aureus is 0.625 mg / mL [Bai Xue, Lin Chen, et al. Experimental study on the antibacterial activity of the extracts of Geum aleppicum and Adina rubella in vitro [J]. Chinese Materia Medica, 2008, 39(10): 1532 - 1534];

[0016] The activities against respiratory syncytial virus (RSV) and coxsackievirus B3 (CVB3) were tested, and the results showed that 3 flavonoid glycosides exhibited antiviral activities against these two viruses to varying degrees [Li Yaolan, et al. Flavonoid components of Adina rubella and their antiviral activities in vitro [J]. Research and Development of Natural Medicines, 2009, 21(8): 741 - 743].

[0017] Taking Chenopodium ambrosioides as the monarch drug, which is pungent and warm in nature, can disperse cold and regulate qi, relieve epigastric pain and abdominal distension; Adina rubella is slightly cold in nature, can promote blood circulation and remove blood stasis, make qi and blood smooth, and also has the effects of stopping bleeding and promoting granulation, clearing heat and promoting diuresis: the combination of the two drugs can achieve the effects of regulating qi and dispersing cold, relieving pain, clearing heat, promoting blood circulation and promoting granulation.

[0018] Chinese patent document CN109260161A "Jinghua Weikang Pills and Its Preparation Method" records that the traditional Chinese medicine preparation Jinghua Weikang produced by this patent can promote ulcer healing, has an obvious inhibitory effect on gastrointestinal peristalsis, relieves pain, and has obvious advantages over antibiotics.

[0019] Literature records that the cure rate of chronic superficial gastritis treated with Jinghua Weikang Pills is 74.4%, and the cure rate of duodenal ulcer is 83.3% [Liang Jie, et al. Treatment of 85 cases of chronic upper digestive tract diseases with Jinghua Weikang Capsules [J]. Chinese Journal of New Drugs, 2001, 10(3): 226 - 227].

[0020] According to the annotation in "Chinese Herbal Medicine": it belongs to the liver, spleen, and large intestine meridians; clears heat and removes dampness; disperses stasis and relieves pain; stops bleeding and astringes sores. It is mainly used for dysentery and enteritis; the combination of Chenopodium ambrosioides and Adina rubella is specific for enteritis. Patent document CN 109260161 A records that its patent document adds excipients such as propylene glycol, Tween, poloxamer, hydroxypropyl-β-cyclodextrin, lactitol, polyoxyethylene monostearate, and carrageenan and is dropwise prepared to obtain Jinghua Weikang Pills. Judging from the composition of the excipients, it belongs to a gastric-soluble preparation.

[0021] Due to the dissolution of gastric-soluble preparations in the gastric acid environment, there is a risk of decomposition of the pharmacodynamic components by gastric acid, pepsin, etc., or the concentration of the pharmacodynamic components is significantly reduced when reaching the intestine, reducing the effectiveness of treating intestinal diseases.

[0022] There are significant differences between gastric-coated and enteric-coated formulations for oral administration. Gastric-coated drugs disintegrate and dissolve in the acidic environment of the stomach and are mainly absorbed through the gastric mucosal epithelial cells. Enteric-coated drugs disintegrate and dissolve in the alkaline environment of the intestine, and the absorption site is the intestinal wall. The large surface area and high blood flow of the intestinal wall are conducive to the absorption of the active ingredients. After oral administration, the active ingredients of the drug disintegrate and dissolve in the gastrointestinal tract in the form of molecules or ions. They need to penetrate the gastrointestinal membrane to enter the bloodstream and exert their therapeutic effect. In this process, in addition to the physicochemical properties of the active ingredients themselves and the body's own physiological factors, different dissolution environments have an important influence on the absorption of the active ingredients. For the formulation of *Artemisia argyi* and *Hedyotis diffusa*, which is indicated for enteritis, the enteric-coated dosage form is more reasonable than the gastric-coated form. Summary of the Invention

[0023] The first objective of this invention is to provide an enteric-coated formulation of *Euphorbia pekinensis* and *Hylocereus undatus* for the treatment of enteritis; the second objective is to provide a method for preparing an enteric-coated formulation of *Euphorbia pekinensis* and *Hylocereus undatus*.

[0024] Technical solution for realizing the present invention

[0025] To achieve the first objective mentioned above, the technical solution of the present invention is to prepare an enteric-coated formulation using the active ingredients of *Euphorbia hirta* and *Euphorbia humifusa*, and excipients; the enteric-coated formulation includes enteric-coated soft capsules and enteric-coated pellets.

[0026] The enteric-coated soft capsules comprise the active ingredients of *Eupatorium fortunei* and *Hypericum perforatum*, and are composed of Class I excipients.

[0027] The medicinal components of *Artemisia annua* and *Artemisia scoparia* are the volatile oils of *Artemisia annua* and *Artemisia scoparia*.

[0028] Among them, the volatile oil of *Artemisia annua* and the volatile oil of *Hydrocotyle vulgaris* are extracted from the following raw medicinal materials in the following weight ratio: *Artemisia annua*: *Hydrocotyle vulgaris* = 50-70: 30-50.

[0029] The first type of excipient is the shell material of enteric-coated soft capsules, and the second type of excipient is the excipient matrix of enteric-coated pellets and the coating film.

[0030] The first type of enteric soft capsule shell material includes gelatin, glycerin, and distilled water; wherein gelatin is a film-forming agent, glycerin is a plasticizer, and distilled water is a solvent.

[0031] The gelatin to glycerol ratio should be between 4:1 and 1:2. Increasing the gelatin to glycerol ratio increases flow resistance and gelatin hardness. When the ratio exceeds 4:1, the viscosity and flowability of the solution exceed the requirements of the soft capsule preparation process, and the gelatin shell becomes too hard, losing the softness of the soft capsules. A gelatin to glycerol ratio between 3:1 and 1:1 is more suitable. Regarding the distilled water to gelatin ratio, increasing the ratio (>2) results in a thin solution with poor gelatin elasticity, making it prone to breakage. When the ratio is less than 1, the gelatin's swelling effect is poor. A ratio between 1:2 and 2:1 is more suitable. The preferred ratio is: Gelatin:Glycerol:Distilled Water = 2:1:2.

[0032] Melt temperature: Select 70℃~80℃; above 80℃, the moisture evaporates quickly and the viscosity stability of the adhesive is poor; below 70℃, the melting time is long. Select 70℃ as the melt temperature.

[0033] Selection of soft capsule shell thickness: 0.8mm~1mm; >1mm: slow drying and forming, low drug loading ratio; <0.8mm: easy to break during drying and forming process; 0.8mm is selected, with dimensions φ8mm×L6mm;

[0034] Temperature control of the glue solution during the pelleting process: The temperature of the glue solution during the pelleting process is maintained at 64℃±0.5℃, and the pellet pressing temperature is 22℃±3℃.

[0035] The soft capsules are filled with 80mg of volatile oil from *Gnaphalium affine* and *Hydrocotyle vulgaris*.

[0036] When soft capsules made of gelatin and glycerin enter the gastric environment, the surface of the soft capsule comes into contact with gastric acid, causing the gelatin layer to swell. The swollen surface forms the capsule wall, preventing gastric acid from dissolving the inner capsule layer. The drug encapsulated in the inner capsule layer is sealed by the undissolved inner capsule layer. Gelatin has excellent gelling properties, enabling it to further gelatinize the surface of the swollen capsule, forming a soft capsule wall. This gelled surface structure further prevents gastric acid from penetrating the soft capsule shell, thus ensuring the stability of the drug within the capsule in a sealed state within the gastric environment. Gelatin has good solubility in an alkaline environment. After the soft capsule surface swells in gastric acid, it enters the intestines under the peristalsis of the stomach and intestines. In the alkaline environment of the intestines, the capsule wall, the gelled surface, and the inner capsule layer gradually dissolve in sequence. The time it takes for the capsule to puncture is related to the thickness of the capsule shell. After puncture, the drug inside the capsule is released into the intestinal environment, thus achieving the purpose of targeted drug release.

[0037] The enteric-coated pills include the active ingredients of *Eupatorium fortunei* and *Hydrocotyle vulgaris*, and second-class excipients;

[0038] The medicinal components of *Artemisia annua* and *Artemisia scoparia* are the volatile oils of *Artemisia annua* and *Artemisia scoparia*.

[0039] The second type of excipients includes excipient matrix components, Group A coating film components, and Group B coating film components;

[0040] The excipient matrix components are prepared by using dispersion technology to fully disperse the volatile oils of *Euphorbia tirucalli* and *Hydrocotyle vulgaris* in the water-soluble excipient matrix to prepare droplet cores.

[0041] The excipient matrix components include polyethylene glycol 4000 and polyethylene glycol 6000;

[0042] The components of group A and group B of the coating film mentioned above are enteric coatings;

[0043] Enteric coating prevents the drug from decomposing in acidic conditions such as the stomach, thereby improving the drug's bioavailability in the body.

[0044] The A-group coating film component is hydroxypropyl methylcellulose phthalate, abbreviated as (HPMCP);

[0045] The components of the B-group coating film are acrylic resin, Tween-80, castor oil, polyethylene glycol 6000, and 95% ethanol.

[0046] To achieve the second objective mentioned above, the method includes: a method for preparing enteric-coated soft capsules using a formula of *Euphorbia pekinensis* and *Hydrocotyle vulgaris*, and a method for preparing enteric-coated droplets using a formula of *Euphorbia pekinensis* and *Hydrocotyle vulgaris*.

[0047] The preparation method includes the extraction of the active ingredients of *Euphorbia pekinensis* and *Euphorbia hirta*; a method for preparing enteric-coated soft capsules and a method for preparing enteric-coated pellets;

[0048] A method for preparing an enteric-coated formulation using *Euphorbia pekinensis* and *Hylocereus undatus* comprises the following steps: extraction of the active ingredients from *Euphorbia pekinensis* and *Hylocereus undatus*, and preparation of the enteric-coated formulation.

[0049] Extraction of medicinal components from *Cynanchum paniculatum* and *Hylocereus undatus*:

[0050] Step 1: Formulating the prescription, weigh the *Nepeta cataria* and *Hylocereus undatus* according to the specified proportions;

[0051] Step 2: Chop. Chop the *Nepeta cataria* and *Hedyotis diffusa* herbs into pieces, with a length of ≤0.5cm;

[0052] Step 3: Soaking. Soak the chopped *Artemisia annua* and *Artemisia argyi* herbs in a solvent.

[0053] Step 4: Wet crushing. The herbs, including the solvent, that have been soaked in the solvent are crushed using a high-speed shearing machine. Herbs with a length ≤ 0.855 mm are crushed until they pass through a 20-mesh sieve.

[0054] Step 5: Solid-liquid separation. The solid-liquid mixture after wet grinding is separated into solid and liquid phases using a centrifuge or plate and frame filter. The filtrate is collected, and the residue is discarded.

[0055] Step 6: Distillation. Collect the volatile oil by distilling the filtrate using a thin-film evaporator.

[0056] Step 7: Remove moisture. Use a low-temperature centrifuge to separate the moisture from the collected volatile oil to obtain anhydrous volatile oil.

[0057] Step 8: Encapsulate soft capsules and prepare enteric-coated droplets;

[0058] The aforementioned encapsulated soft capsules are made by filling anhydrous volatile oil into prepared soft capsules and then encapsulating them.

[0059] The preparation of enteric-coated pellets involves dispersing anhydrous volatile oil in the excipient matrix to prepare pellet cores, and then coating the pellet cores with an enteric coating.

[0060] in:

[0061] Step three: soaking. Soak the chopped Artemisia annua and distilled water-soaked herbs in a solvent. The solvent is distilled water, and the solid-liquid ratio of the herbs to the solvent is 1:10 to 1:15. Soak for 8 to 24 hours to allow the herbs to fully absorb water and swell.

[0062] Step four, wet pulverization, involves using a high-speed shearing machine to cut the *Artemisia capillaris* and *Artemisia argyi* herbs (including the solvent) that have been soaked in the solvent. Herbs ≤0.5cm in length are cut until they pass through a 20-mesh sieve. The herbs, having fully absorbed water and swelled, are subjected to shearing and compression during the high-speed shearing process, creating a pulverizing effect. This exposes more of the herb tissue to the solvent, allowing the volatile oils in the herbs to diffuse into the solvent. The compression force further diffuses the volatile oils from the herb tissue into the solvent under mechanical force. This process, with more cross-sections in contact with the solvent, ensures that the volatile oils are fully dissolved in the solvent. This process replaces the heating and cooking process, avoiding the destruction of heat-sensitive components in the volatile oils caused by heating and cooking.

[0063] Step six: distillation, the filtrate is distilled and the volatile oil is collected using a thin-film evaporator; the thin-film evaporator includes a falling film scraped film evaporator and a vacuum thin-film evaporator.

[0064] The aforementioned thin-film evaporator distillation method for collecting volatile oils involves the filtrate from solid-liquid separation in step five being distributed as a thin film on the heat transfer wall of the evaporator. This method offers high heat transfer efficiency, short material heating time, reduced heating time for heat-sensitive components, lower evaporation temperature, and avoids decomposition of heat-sensitive components due to prolonged heating.

[0065] Step seven: Remove moisture by using a low-temperature centrifuge to separate the moisture from the collected volatile oil to obtain anhydrous volatile oil;

[0066] The method described involves separating water using a low-temperature centrifuge. The process is as follows: the centrifuge drum temperature is set to -6.5℃ to -5.5℃. The volatile oil flows and rotates within the centrifuge drum. Due to gravity, substances of different masses separate. When water molecules come into contact with the drum wall, they form heterogeneous nuclei on the drum surface. As the drum rotates continuously, the water molecules continuously nucleate and aggregate, eventually forming ice crystals. The liquid water phase in the volatile oil transforms into a solid, adhering to the inner wall of the drum, while the volatile oil components remain in the liquid phase. The liquid phase is then removed, thus achieving oil-water separation and obtaining anhydrous volatile oil.

[0067] Step eight, preparation of enteric-coated soft capsules and enteric-coated pellets:

[0068] The method for preparing enteric-coated soft capsules includes preparing soft capsule gel, preparing soft capsule shell, filling and encapsulating the anhydrous volatile oil in the soft capsule shell, and sewing the filling opening to seal the soft capsule.

[0069] The encapsulation of the soft capsules involves filling the prepared soft capsules with anhydrous volatile oil and then encapsulating them; the process includes the following steps;

[0070] Step 1: Ingredient preparation; Weigh and prepare gelatin, glycerin, and distilled water in a ratio of 2:1:2 by weight.

[0071] Step 2: Sol preparation; Weigh and prepare the gelatin, glycerin, and distilled water; First, add water to the sol tank. When the water temperature reaches 70℃, add glycerin to the sol tank and stir until homogeneous. Then, add gelatin to the sol tank and stir to dissolve the gelatin, obtaining a sol solution with a viscosity of 39-45 mPa·s and a constant temperature of 70℃. The sol tank is a container with heating, heat preservation, stirring, and vacuum functions.

[0072] Step 3: Degassing; After step 2 is completed, turn on the vacuum function of the sol tank to remove the gas trapped in the sol liquid, so as to prevent the gas trapped in the sol liquid from causing the capsules prepared in step 4 to form pores.

[0073] Step 4: Capsule forming; The prepared sol solution is used to form capsules using a soft capsule machine. The soft capsule machine has functions such as mold roller alignment, cutting timing, filling weight measurement, and gelatin tape thickness adjustment. The soft capsule preparation process includes capsule forming, filling with anhydrous volatile oil, capsule sewing, and demolding.

[0074] Step 5: Drying; After the capsules are demolded, the moisture content of the capsule shells needs to be treated to achieve the purpose of capsule shaping and quality stabilization. Step 5: Drying is carried out using a special dryer for soft capsules. The special dryer for soft capsules has the functions of rotary drum shaping and drying, and tray static drying. The drying process in Step 5 is as follows: First, rotary drum shaping and drying is used to remove some moisture, reducing the moisture content of the capsule shells to the point where the capsules are shaped. Then, the capsules enter the tray static drying stage for static drying. The static drying stage controls the moisture content of the capsules to 8% to 12%. If the moisture content is >12%, the capsule shells are prone to mold; if the moisture content is <8%, the capsule shells are prone to cracking, which is not conducive to storage and transportation.

[0075] The method for preparing enteric-coated pellets includes pellet core preparation, coating solution preparation, and pellet core coating.

[0076] The enteric-coated pellets include the anhydrous volatile oil, the second type of excipients, the pellet core, and the enteric coating.

[0077] The second type of excipients includes excipient matrix components, group A coating film components, and group B coating film components;

[0078] The excipient matrix components are polyethylene glycol 4000 and polyethylene glycol 6000;

[0079] The A-group coating film component is hydroxypropyl methylcellulose phthalate, abbreviated as (HPMCP);

[0080] The components of the B-group coating film are acrylic resin, Tween-80, castor oil, and polyethylene glycol 6000;

[0081] The coating film components of Group A and Group B shall be selected from one of them;

[0082] Preparation of the droplet core;

[0083] The ratio of drug to excipient matrix is ​​1:1 to 1:1.8;

[0084] The drug is the volatile oil extracted from the combination of *Artemisia argyi* and *Hylocereus undatus*.

[0085] The excipient matrix is ​​polyethylene glycol 4000 or polyethylene glycol 6000;

[0086] The aforementioned polyethylene glycol 4000 and polyethylene glycol 6000 are water-soluble;

[0087] The aforementioned polyethylene glycol 4000 is a versatile polymer material widely used in pharmaceuticals, chemistry, and materials science. Its melting point is 55℃±2℃.

[0088] The aforementioned polyethylene glycol 6000 is commonly used as a pharmaceutical excipient, such as in the preparation of suppositories, ointments, and drops, and has a melting point of 57℃±2℃.

[0089] The aforementioned droplet core, with optimized ratio of drug to excipient matrix;

[0090] The ratio of drug to excipient matrix has a certain impact on pellet formation. Generally, the higher the drug ratio, the worse the pellet formation and bioavailability. Although the pellet formation rate is high, the drug loading is small and the dosage will be increased. Therefore, in order to improve the drug loading and pellet core forming, the ratio of drug to excipient matrix is ​​optimized.

[0091] The drug-to-matrix ratio was optimized to 1:1 to 1:1.4. The viscosity increased as the proportion of the matrix decreased, making drop preparation difficult. The drug-to-matrix ratio was 1:1.6 to 1.8. The texture of the droplets became softer as the proportion of the matrix increased, and the uniformity of roundness was poor.

[0092] Selection: The drug-to-matrix ratio is 1:1.5;

[0093] The excipient matrix is ​​a combination of polyethylene glycol 4000 and polyethylene glycol 6000;

[0094] The aforementioned polyethylene glycol polymers are readily soluble in water, have low melting points, and good chemical stability. They can increase the solubility and dissolution rate of drugs, and also have good dispersing power and large cohesive power. They are widely used and belong to a relatively ideal class of carrier matrices. The common approach is to use a combination of polyethylene glycol 4000 and polyethylene glycol 6000.

[0095] Different combinations of polyethylene glycol 4000 and polyethylene glycol 6000 in different proportions result in different process outcomes.

[0096] This scheme selects a combination ratio of polyethylene glycol 4000 to polyethylene glycol 6000 within the range of 3:7 to 6:4 for optimization;

[0097] When the proportion of polyethylene glycol 4000 is less than 4% and polyethylene glycol 6000 is greater than 7%, the prepared droplets are relatively viscous.

[0098] When the proportion of polyethylene glycol 4000 is greater than 6% and the proportion of polyethylene glycol 6000 is less than 4%, the prepared droplets are too viscous and too thin, and the uniformity of the sphericity of the droplets is poor.

[0099] The ratio of polyethylene glycol 4000 to polyethylene glycol 6000 is selected as 4:6;

[0100] The preparation of droplets from a drug-matrix mixture is a hot-melt mixture. The droplet forming process requires a cooling step, which necessitates a coolant. The coolant formulation must be selected based on the properties of the drug-matrix mixture. Since both polyethylene glycol 4000 and polyethylene glycol 6000 are water-soluble matrices, an oil-based liquid is required as the coolant. Three commonly used oil-based liquid coolants are vegetable oil, dimethyl silicone oil, and liquid paraffin. The optimization of these three coolants was investigated, and their performance parameters are listed in Table 1.

[0101] Table 1. Optimization data for three commonly used oily liquid coolants

[0102] Coolant categories Droplet manufacturing process vegetable oil The pellets settled too quickly, falling to the bottom and sticking together before they could solidify. Dimethyl silicone oil The pellets have a moderate settling rate and good roundness in the finished product. Liquid paraffin The pellets settle quickly, resulting in poor sphericity of the finished product.

[0103] The above results indicate that dimethyl silicone oil is the most suitable coolant for the dripping process.

[0104] The preparation of the drop pellet core involves, based on the optimization process of the three cooling liquids, adding the anhydrous volatile oil to a 4:6 mixture of polyethylene glycol 4000 and polyethylene glycol 6000 at a drug-to-excipient matrix ratio of 1:1.5, heating to melt, stirring evenly, using dimethyl silicone oil as the cooling liquid at a temperature of 5℃~10℃, and using a drop pellet machine to drop the drop pellet core.

[0105] The aforementioned droplet core coating refers to the thin film covering the outer layer of the droplet core, which is an enteric coating material. This coating ensures that the droplet core remains insoluble in gastric juice but dissolves in intestinal juice, releasing the drug from the core. This prevents the drug from being destroyed by gastric juice and avoids irritation to the stomach.

[0106] The enteric coating material includes Group A coating film components and Group B coating film components;

[0107] The A-group coating film component is hydroxypropyl methylcellulose phthalate, abbreviated as (HPMCP);

[0108] The components of the B-group coating film are acrylic resin, Tween-80, castor oil, and polyethylene glycol 6000;

[0109] The hydroxypropyl methylcellulose phthalate (HPMCP) is a high-performance enteric coating film component. Based on its dissolution pH, it can be divided into HP55 and HP50 types. HP55 requires a pH of 5.5 to dissolve, while HP50 requires a pH of 6.0. The pH of the upper to lower part of the human duodenum is 5.0 to 6.0. Therefore, HPCP coating, whether HP55 or HP50, is an enteric coating film that can dissolve in the upper part of the duodenum.

[0110] The composition and preparation method of the coating solution for the coating film components of group A;

[0111] The coating solution consists of: HPMCP 2%–9%; ethanol 45.5%–49%; acetone 45.5%–49%.

[0112] The optimization of the composition and structure of the coating solution in group A:

[0113] When HPMCP < 2%, the coating film is too thin and it is difficult to form a complete film; when HPMCP > 9%, the coating solution is too viscous, resulting in uneven coating film thickness.

[0114] Selection: HPMCP 5% : Ethanol 47.5% : Acetone 47.5%

[0115] The preparation of the coating solution of group A is carried out according to the following steps:

[0116] Step 1: Sol;

[0117] Step 2: Degassing;

[0118] The sol is prepared by adding HPMCP at a concentration of 2%–9%, ​​ethanol at a concentration of 45.5%–49%, and acetone at a concentration of 45.5%–49% into a stirred sol container, stirring, and heating to 65°C to melt the HPMCP completely.

[0119] The degassing process involves turning on the vacuum equipment of the stirring sol tank after HPMCP has been fully dissolved to remove gas from the HPMCP solution, thus preventing the formation of bubbles or pores in the coating film during the coating process.

[0120] Step 3: Collect the coating solution for group A;

[0121] The composition and preparation method of the coating solution for the coating film components of group A;

[0122] The composition and formulation of the coating solution in group B are as follows:

[0123] The components of the B-group coating film include acrylic resin; Tween-80, castor oil, and polyethylene glycol 6000; wherein the acrylic resin includes acrylic resin II and acrylic resin III;

[0124] The acrylic resin II described is an anionic methacrylic acid copolymer, insoluble in gastric juice but soluble in intestinal juice. It is mainly used as a coating for enteric-coated oral tablets, capsules, pills, and granules. It can also be used in the manufacture of capsules, films, etc., to regulate the drug release site, and commonly uses 85-95% ethanol as a solvent.

[0125] Acrylic resin II and acrylic resin III are soluble in ethanol and methanol, but insoluble in water and acids. Acrylic resin II dissolves above pH 6.0, and acrylic resin III dissolves above pH 6.5. Most enteric-coated formulations currently use a mixture of acrylic resin II and acrylic resin III for coating. Acrylic resin II has the advantages of high solids content and low viscosity, making it less prone to tablet sticking and pan adhesion, resulting in uniform coating and a smooth coating layer. Acrylic resin III easily forms a film with good surface gloss, but it is prone to sticking. In practical applications, mixing acrylic resin II and acrylic resin III in an appropriate ratio can overcome the tendency to stick while maintaining the advantages of easy film formation and good surface gloss. Adjusting the ratio of the two can also adjust the solubility at different pH values. Acrylic resins are enzyme-resistant and have low drug permeability. The process involves preparing a coating solution using acrylic resin II and acrylic resin III in an appropriate ratio, and then coating the pellet cores using a coating device.

[0126] Adding an appropriate amount of plasticizer can improve the toughness of the coating film. The plasticizer includes one of triethyl citrate and polyethylene glycol 6000.

[0127] The coating solution includes the additives: Tween-80, castor oil, polyethylene glycol 6000, and the solvent: 95% ethanol.

[0128] Tween-80 is a solubilizer that enables oily substances and water to mix better. Its hydrophilic and lipophilic groups in its molecular structure reduce surface tension, thus eliminating foam and forming a stable mixture. In this solution, it solubilizes acrylic resin and polyethylene glycol 6000 and eliminates foam in the coating solution.

[0129] Castor oil has good compatibility and plasticizing properties with resins, rosin, shellac, etc., and plays a role in optimizing the film formation of the coating solution in this solution.

[0130] The composition and formulation of the acrylic resin coating solution are listed in Table 2.

[0131] Table 2. Composition of acrylic resin coating solution (w / w)

[0132]

[0133] Preparation of the coating solution of group B:

[0134] Follow these steps:

[0135] Step 1: Sol;

[0136] Step 2: Degassing;

[0137] The sol is prepared by adding acrylic resin II, acrylic resin III, Tween-80, castor oil, polyethylene glycol 6000, and 95% ethanol into a stirring and melting tank, stirring, and heating to 65°C to fully dissolve acrylic resin II, acrylic resin III, and polyethylene glycol 6000, resulting in homogeneous and uniform sol.

[0138] The degassing process involves fully dissolving acrylic resin II, acrylic resin III, and polyethylene glycol 6000, ensuring the six materials are homogeneous. Then, the vacuum equipment in the stirring sol tank is activated to remove the gas trapped in the mixture of acrylic resin II, acrylic resin III, polyethylene glycol 6000, Tween-80, and castor oil, thus preventing the formation of bubbles or pores in the coating film during the coating process.

[0139] Step 3: Collect the coating solution for group B.

[0140] The method for preparing the pellet core comprises the following steps:

[0141] (1) Put 320g of polyethylene glycol 4000 and 513g of polyethylene glycol 6000 into a melting pot and heat them to melt at 70°C to prepare the adhesive solution.

[0142] (2) After polyethylene glycol 4000 and polyethylene glycol 6000 are fully melted, 570g of the anhydrous volatile oil is added slowly in a thin stream to prepare droplets.

[0143] (3) Stir evenly to make the components in the droplet liquid homogeneous;

[0144] (4) Degassing; turn on the vacuum equipment of the stirring melt tank to remove the gas in the melt tank and the gas trapped in the droplets;

[0145] (5) The pellets are dropped into the coolant dimethyl silicone oil at a rate of 60 drops per minute by the pellet dropping machine. The temperature of the coolant dimethyl silicone oil is 10℃±1℃.

[0146] (6) Collect the pellet cores.

[0147] The coating mentioned above;

[0148] The pellet core is coated with a coating to prevent the drug from decomposing under acidic conditions such as the stomach; the coating materials are selected from the coating solutions of group A and group B.

[0149] The coating preparation is carried out in the following steps.

[0150] The pellet cores are placed into a rotating coating pan. The hot air heating system of the coating pan is started, and the spray pump sprays the coating liquid onto the pellet cores in the rotating coating pan. The pellet cores tumble with the rotating coating pan. The surface of the tumbling pellet cores is sprayed with either the coating liquid of group A or group B. Under the blowing of the hot air heating system of the coating pan at 37°C to 39°C, the film-forming components in the coating liquid are fixed on the surface of the pellet cores, and the liquid phase components in the coating liquid evaporate upon heating. The pellet cores are completely coated with an enteric coating, and a thin coating film is added to the surface of each pellet core.

[0151] The advantages of this invention are:

[0152] This invention relates to an enteric-coated formulation of *Eupatorium fortunei* and *Hypericum perforatum*, which provides a treatment option for intestinal diseases. The drug does not readily dissolve in the stomach but dissolves upon reaching the intestines, avoiding the irritation of the stomach by the drug's odor. This improves patient compliance. It avoids the destruction of the drug by stomach acid, increasing the concentration of the active ingredient in the intestines and enhancing the efficacy against intestinal diseases. The enteric-coated formulation does not disintegrate in the stomach but disintegrates in the intestines, allowing the active ingredient to remain in the intestines for a longer period, prolonging the drug's action, increasing drug stability and local therapeutic effect.

[0153] The present invention provides a method for preparing enteric-coated soft capsules containing a formula of *Euphorbia pekinensis* and *Hylocereus undatus*, which has the following advantages:

[0154] ① A process combining soaking and swelling of medicinal herbs with wet pulverization was adopted to replace the existing decoction process. High-speed shearing was used to fully swell the herbs, which were then crushed and compressed at a frequency exceeding 20,000 times / min, creating a juicing effect. The active ingredients diffused and dissolved into the solvent without heating, avoiding the heat-sensitive components that would be destroyed during decoction. This also prevented the gelatinization of colloidal substances in the herbs during decoction, which would hinder the diffusion and dissolution of active ingredients, thus improving the yield of active ingredients.

[0155] ② A solid-liquid separation process was adopted to obtain the extract. The solid and liquid phases were separated by a centrifuge or plate and frame filter, and the filtrate was distilled to extract the volatile oil. Compared with the existing method of directly boiling medicinal materials to extract volatile oil, this method can avoid the adsorption of a large amount of medicinal fiber on volatile oil, which would reduce the yield of volatile oil; thus improving the bioavailability of medicinal materials.

[0156] ③ A thin-film distillation process was adopted, using a falling film scraped film evaporator and a vacuum thin-film evaporator to extract volatile oils. The distillate is distributed as a thin film on the heat transfer wall of the evaporator, resulting in high heat transfer efficiency, short material heating time, reduced heating time for heat-sensitive components, lower evaporation temperature, and prevention of thermal decomposition of heat-sensitive components, thereby improving the bioactivity of the extracted volatile oils. Simultaneously, energy consumption was saved.

[0157] ④ The extracted volatile oil underwent dehydration treatment. Based on the physical characteristics that volatile oil and water have different phase transition crystallization temperatures, a low-temperature centrifuge was used to separate the water from the volatile oil. When water molecules come into contact with the drum wall of the low-temperature centrifuge, they immediately form heterogeneous nuclei on the drum wall. As the drum rotates continuously, the water molecules continuously nucleate and aggregate, eventually forming ice crystals. The liquid water phase in the volatile oil changes to a solid phase and adheres to the inner wall of the drum, while the volatile oil components remain in the liquid phase. The liquid phase is then removed, thus achieving oil-water separation and obtaining anhydrous volatile oil. Separating and removing the mixed water from the volatile oil can increase the concentration of the active pharmaceutical ingredients, improve the efficacy, and also benefit the quality stability of the drug's shelf life.

[0158] Compared with existing methods for removing residual moisture from volatile oils, which mainly rely on anhydrous sodium sulfate adsorption technology, anhydrous sodium sulfate crystals adsorb a large amount of volatile oil. As a result, the volatile oil treated with anhydrous sodium sulfate adsorption will contain residual sodium sulfate, which will affect the quality of the volatile oil. Detailed Implementation

[0159] The present invention will be further described below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the description of this invention, those skilled in the art can make various alterations or modifications to the invention, and these equivalent forms also fall within the scope defined by the appended claims.

[0160] Example 1

[0161] The enteric-coated preparation of *Gnaphalium affine* and *Hylocereus undatus* consists of the active ingredients of *Gnaphalium affine* and *Hylocereus undatus*, and pharmaceutical excipients, and is prepared into enteric-coated soft capsules; the active ingredients are the volatile oils of *Gnaphalium affine* and *Hylocereus undatus*, and the pharmaceutical excipients are gelatin, glycerin, and distilled water for preparing the enteric-coated soft capsules;

[0162] Weigh out the following raw materials according to the weight ratio: 70 parts of *Artemisia argyi* and 50 parts of *Symplocos natans*.

[0163] The preparation method includes the following steps:

[0164] (1) Take 7000g of *Nepeta cataria* and 5000g of *Hedyotis diffusa*;

[0165] (2) Chop into small pieces, with a length of ≤0.5cm;

[0166] (3) Soak in 180 liters of solvent for 8 hours. The solvent is distilled water.

[0167] (4) Wet pulverization: The soaked medicinal materials, including the solvent, are sheared using a high-speed shearing machine. The length of the sheared medicinal materials is ≤0.85mm and they pass through a 20-mesh sieve.

[0168] (5) Solid-liquid separation: The solid-liquid mixture after wet grinding is filtered and separated into solid and liquid phases using a filter centrifuge. The filtrate is collected, the residue is discarded, and 150 liters of filtrate are obtained.

[0169] (6) Distillation: 439.2g of initial volatile oil was obtained by vacuum thin-film evaporator distillation;

[0170] (7) Remove moisture by using a low-temperature centrifuge to obtain 366g of anhydrous volatile oil;

[0171] (8) Encapsulation of soft capsules;

[0172] The encapsulation of the soft capsule is carried out according to the following steps:

[0173] (8.1) Weigh and mix the pharmaceutical excipients gelatin, glycerin, and distilled water in a weight ratio of 2:1:2.

[0174] (8.2) Add glycerin and water to the sol tank, stir and heat to make the glycerin and water uniform, and raise the temperature to 70°C;

[0175] (8.3) Add gelatin to a sol tank and stir to dissolve the gelatin to prepare a sol solution;

[0176] (8.4) Degassing: Turn on the vacuum pump of the sol tank to remove the gas entrained in the sol solution;

[0177] (8.5) Sol viscosity test: The viscosity of the sol solution shall be within the range of 39 to 45 mPa·s;

[0178] (8.6) Pelletizing: The sol solution is used to prepare soft capsule shells; the soft capsule shells are olive-shaped, with a size of 8mm×6mm and a thickness of 0.75~0.8mm;

[0179] (8.7) Charge with 80 mmg of anhydrous volatile oil;

[0180] (8.8) Suturing: Sew the soft capsule shell closed;

[0181] (8.9) Demolding: The soft capsules are discharged from the pelleting machine;

[0182] (8.10) Drying: The soft capsules obtained from the mold are put into a rotary dryer for drying to reduce some of the moisture in the soft capsule shell and fix the soft capsule shape.

[0183] (8.11) Secondary drying: After drying in a rotary dryer, the soft capsules are placed into a tray for drying, so that the moisture content in the soft capsule shell is controlled at 8% to 12%.

[0184] 4575 enteric-coated soft capsules containing the ingredients of *Eupatorium fortunei* and *Hylocereus undatus* were prepared.

[0185] Example 2

[0186] The enteric-coated preparation of *Gnaphalium affine* and *Hylocereus undatus* consists of the active ingredients of *Gnaphalium affine* and *Hylocereus undatus*, and pharmaceutical excipients, and is prepared into enteric-coated soft capsules; the active ingredients are the volatile oils of *Gnaphalium affine* and *Hylocereus undatus*, and the pharmaceutical excipients are gelatin, glycerin, and distilled water for preparing the enteric-coated soft capsules;

[0187] Weigh out the following raw materials according to the weight ratio: 70 parts of *Artemisia argyi* and 50 parts of *Symplocos natans*.

[0188] The preparation method includes the following steps:

[0189] (1) Take 7000g of *Nepeta cataria* and 5000g of *Hedyotis diffusa*;

[0190] (2) Chop into small pieces, with a length of ≤0.5cm.

[0191] (3) Soak in 180 liters of solvent for 8 hours. The solvent is distilled water.

[0192] (4) Wet pulverization: The soaked medicinal materials, including the solvent, are sheared using a high-speed shearing machine. The length of the sheared medicinal materials is ≤0.85mm and they pass through a 20-mesh sieve.

[0193] (5) Solid-liquid separation: The solid-liquid mixture after wet grinding is filtered and separated into solid and liquid phases using a plate and frame filter. The filtrate is collected, the residue is discarded, and 126 liters of filtrate is obtained.

[0194] (6) Distillation was carried out using a falling film scraped film evaporator to obtain 410.5g of initial volatile oil;

[0195] (7) Remove moisture by using a low-temperature centrifuge to obtain 342g of anhydrous volatile oil;

[0196] (8) Encapsulate the soft capsule; complete the process according to steps (8.1) to (8.11) as described in Example 1;

[0197] 4275 enteric-coated soft capsules containing the ingredients of *Eupatorium fortunei* and *Hylocereus undatus* were prepared.

[0198] The difference between the preparation methods of Examples 1 and 2 is that step five is solid-liquid separation and step six is ​​distillation. The comparison shows that the yield of anhydrous volatile oil in Example 1 is 7% higher than that in Example 2; the filtrate yield in step five, solid-liquid separation, is higher in Example 1 than in Example 2.

[0199] Example 3

[0200] Take the anhydrous volatile oil from Example 1, and the excipient matrix of the pharmaceutical excipients, polyethylene glycol 4000 and polyethylene glycol 6000;

[0201] The preparation method includes the following steps:

[0202] (1) Put 192g of polyethylene glycol 4000 and 307.8g of polyethylene glycol 6000 into a melting tank and heat them to melt at a temperature of 70°C to prepare the adhesive solution;

[0203] (2) After polyethylene glycol 4000 and polyethylene glycol 6000 are fully melted, 342g of the anhydrous volatile oil is added slowly in a thin stream to prepare droplets;

[0204] (3) Stir evenly to make the components in the droplet liquid homogeneous;

[0205] (4) Degassing; turn on the vacuum equipment of the stirring melt tank to remove the gas in the melt tank and the gas trapped in the droplets;

[0206] (5) The pellets are dropped into the coolant dimethyl silicone oil at a rate of 60 drops per minute by the pellet dropping machine. The temperature of the coolant dimethyl silicone oil is 10℃±1℃.

[0207] 10,518 pellet cores with a diameter of 5.76 mm were collected. Each pellet core weighed 80 mg.

[0208] (6) Coating: The preparation is carried out according to the following steps.

[0209] (6.1) Select the coating components of group A;

[0210] (6.1.1) Ingredients: 10.5g of hydroxypropyl methylcellulose phthalate; 99.75ml of ethanol; 99.75ml of acetone.

[0211] (6.1.2) Melting adhesive: Put it into a melting pot and heat it to melt it. The heating temperature is 65℃ to fully dissolve HPMCP;

[0212] (6.1.3) Degassing: After HPMCP is fully dissolved, turn on the vacuum equipment of the stirring sol tank to remove the gas entrained in the HPMCP solution and obtain the coating solution.

[0213] (6.1.4) Coating: The pellet cores are placed into a rotating coating pan. The hot air heating system of the coating pan is started. The spray pump sprays the coating liquid onto the pellet cores in the rotating coating pan. The pellet cores tumble with the rotating coating pan. The coating liquid is sprayed onto the surface of the tumbling pellet cores. Under the blowing of the hot air heating system of the coating pan at 37℃~39℃, the liquid phase component in the coating liquid of group A evaporates due to heat, and the film-forming component is fixed on the surface of the pellet core. The pellet cores are completely coated with a layer of coating. The weight gain of a single pellet core is 0.6mg due to the additional coating layer.

[0214] Example 4

[0215] (6.2) Select the coating components of group B;

[0216] (6.2.1) Ingredients: According to the proportions of each component listed in Table 2, take acrylic resin II (4.5g), acrylic resin III (2.0g), Tween-80 (1.65g), castor oil (3.7g), polyethylene glycol 6000 (2.0g), and 95% ethanol (68.5g);

[0217] (6.2.2) Melt adhesive: Add the 6 materials listed in the ingredients to a stirring melting tank and stir. Heat to melt at 65°C to fully dissolve acrylic resin II, acrylic resin III, and polyethylene glycol 6000, so that the 6 materials are homogeneous and uniform, and a homogeneous solution is obtained.

[0218] (6.2.3) Degassing: After HPMCP is fully dissolved, turn on the vacuum equipment of the stirring sol tank to remove the gas entrained in the homogeneous solution and obtain the coating solution.

[0219] (6.2.4) Coating: The pellet cores described in Example 3 are placed into a rotating coating pan. The hot air heating system of the coating pan is started, and the spray pump sprays the coating liquid onto the pellet cores in the rotating coating pan. The pellet cores tumble with the rotating coating pan, and the surface of the tumbling pellet cores is sprayed with the coating liquid. Under the blowing of the 37°C to 39°C hot air heating system of the coating pan, the components of the coating liquid in group B are fixed on the surface of the pellet cores. The liquid phase components in the coating liquid evaporate when heated, and the pellet cores are completely coated with a layer of coating. The weight gain of a single pellet core is 0.8 mg due to the additional coating layer.

[0220] Comparative analysis of Examples 3 and 4 shows that the coatings of hydroxypropyl methylcellulose phthalate, acrylic resin II, acrylic resin III, Tween-80, castor oil, and polyethylene glycol 6000 resulted in a film thickness that was thinner in the former case than in the latter.

Claims

1. An enteric-coated formulation of *Clematis armandii* and *Hylocereus undatus*, characterized in that: The aforementioned preparation of an enteric-coated formulation using the medicinal components and excipients of *Eupatorium fortunei* and *Eupatorium truncatum*. The enteric-coated formulations include enteric-coated soft capsules and enteric-coated pellets; The medicinal components of *Artemisia annua* and *Artemisia scoparia* are the volatile oils of *Artemisia annua* and *Artemisia scoparia*. The aforementioned formula of *Artemisia annua* and *Hylocereus undatus* is a weight ratio of *Artemisia annua* to *Hylocereus undatus* of 50–70: 30–50. The enteric-coated soft capsules include: *Gnaphalium affine*, *Hydrocotyle vulgaris* medicinal components, and Class I excipients; The enteric-coated pills include the active ingredients of *Eupatorium fortunei*, *Hydrocotyle vulgaris*, and Class II excipients; The first type of excipients includes components of enteric-coated soft capsule shell material; The second type of excipients includes enteric-coated pellet excipient matrix and coating film components; The enteric-coated pellet excipient matrix comprises polyethylene glycol 4000 and polyethylene glycol 6000, wherein the ratio of polyethylene glycol 4000 to polyethylene glycol 6000 is 4:

6. The enteric-coated pellets comprise purpureus, volatile oil from water hyacinth, and an enteric-coated pellet excipient matrix, wherein the ratio of purpureus, volatile oil from water hyacinth, and excipient matrix is: optionally 1:1 to 1:1.8, preferably 1:1.5; The coating film components mentioned above include Group A coating film components and Group B coating film components; The A-group coating film components include hydroxypropyl methylcellulose phthalate (HPMCP), ethanol, and acetone; the proportions of each component are optional, such as HPMC 2%–9% : ethanol 45.5%–49% : acetone 45.5%–49%; or, alternatively, HPMC 5% : ethanol 47.5% : acetone 47.5%. The B-group coating film composition includes acrylic resin, Tween-80, castor oil, polyethylene glycol 6000, and ethanol, wherein the acrylic resin includes acrylic resin II and acrylic resin III; the proportions of each component can be selected according to the list in Table 2. Table 2. Composition of acrylic resin coating solution (w / w) 2. A method for preparing an enteric-coated formulation using a combination of *Clematis armandii* and *Hylocereus undatus*, characterized in that... The extraction of medicinal components from *Vitex negundo* and *Hylocereus undatus* follows these steps: Step 1: Formulating the prescription, weigh the *Nepeta cataria* and *Hylocereus undatus* according to the specified proportions; Step 2: Chop. Chop the *Nepeta cataria* and *Hedyotis diffusa* herbs into pieces ≤0.5cm in length; Step 3: Soaking. Soak the chopped *Artemisia annua* and *Artemisia argyi* herbs in a solvent. Step 4: Wet crushing. The medicinal materials of *Artemisia annua* and *Artemisia argyi*, which have been soaked in the solvent, are cut using a high-speed shearing machine. The medicinal materials with a length ≤0.855mm are cut until they pass through a 20-mesh sieve. Step 5: Solid-liquid separation. The solid-liquid mixture after wet grinding is separated into solid and liquid phases using a centrifuge or plate and frame filter. The filtrate is collected, and the residue is discarded. Step 6: Distillation. Collect the volatile oil by distilling the filtrate using a thin-film evaporator. Step 7: Remove moisture. Use a low-temperature centrifuge to separate the moisture from the collected volatile oil to obtain anhydrous volatile oil. In step three, soaking involves immersing chopped Artemisia annua and distilled water in a solvent; the solvent is distilled water, the solid-liquid ratio of the medicinal material to the solvent is 1:10 to 1:15, and the soaking time is 8 to 24 hours. Step four: wet pulverization, the medicinal materials of *Artemisia scoparia* and *Artemisia annua*, which have been soaked in solvent, are cut using a high-speed shearing machine. Medicinal materials with a length ≤0.5cm are cut until they pass through a 20-mesh sieve. Step six: distillation, the filtrate is distilled and the volatile oil is collected using a thin-film evaporator; the thin-film evaporator includes a falling film scraped film evaporator and a vacuum thin-film evaporator; Step seven: Remove moisture. Use a low-temperature centrifuge to separate the moisture from the collected volatile oil to obtain anhydrous volatile oil.

Images