WO2005074952A1 - Chinese medicine for treatment of irritable bowel sysndrome and the preparation thereof - Google Patents

Abstract

The present invention discloses a Chinese medicine treating irritable bowel syndrome, which comprises Pennyroyal and Radix Paeoniae Alba or Radix Paeonia Rubra in a ratio of 1:80-180. It is effective. The present invention also discloses the preparation method thereof.

Description

 Traditional Chinese medicine for treating irritable bowel syndrome and preparation method thereof

 The invention relates to the field of pharmaceutical preparations, in particular to a traditional Chinese medicine for treating irritable bowel syndrome and a preparation method thereof. Background technique

 Irritable bowel syndrome (IBS) is the most common functional disorder of the gastrointestinal tract. It refers to a group including abdominal pain, bloating, abnormal bowel habits and stool characteristics, mucus, persistent or recurrent , And lack of morphological and biochemical abnormalities can explain the symptom group. Western statistics account for about 20% to 40% of patients in the digestive department, and domestic statistics account for about 20% of outpatients in the digestive tract.

13%-52%. However, the etiology and pathogenesis of irritable bowel syndrome are not fully understood so far, and the main purpose of its treatment is to eliminate patients' concerns, improve symptoms, and improve quality of life.

 In terms of chemical drugs, the current clinical research on drugs for the treatment of irritable bowel syndrome is divided into two aspects: on the one hand, terminal organ treatment, mainly for specific symptoms; on the other hand, central treatment, mainly through drug intervention Central nervous system-specific nerve conduction eliminates symptoms of irritable bowel syndrome. Drugs for terminal organ treatment include loperamide, phenebutene, and naloxone; drugs for central treatment, such as antidepressants and anxiolytics. Although the above types of drugs can alleviate some symptoms of irritable bowel syndrome, there are disadvantages in the application that cannot be cured, side effects are large, individual differences are obvious, and treatment costs are high.

In traditional Chinese medicine, traditional Chinese medicine classifies irritable bowel syndrome in the categories of diarrhea, constipation, abdominal pain, stagnation, depression, gathering, intestinal dysfunction, etc. It is believed that it can be caused by exogenous evil qi, internal injury diet, and weak body. Caused by chronic diseases, overwork and other causes, liver stagnation, spleen deficiency, kidney deficiency, stasis, blood stasis and other syndromes are common clinically, and there are many mixed syndromes, but they have different emphasis. According to different classifications, it can be divided into two, three or eight syndrome types, which are usually divided into diarrhea type, constipation type and mixed type three types, among which the diarrhea type is the most common. Traditional Chinese medicine has shown good prospects in the treatment of irritable bowel syndrome. For example, Zhejiang Journal of Integrated Traditional Chinese and Western Medicine 2002, Vol. 12, No. 2, "Traditional Chinese Medicine for 56 Cases of Irritable Bowel Syndrome", Jiangsu Traditional Chinese Medicine, Volume 21 Stage 5 includes "Traditional Chinese Medicine for 47 Cases of Irritable Bowel Syndrome" and so on. In terms of traditional Chinese medicine, the most commonly used methods are to clear the liver, strengthen the spleen, and treat the temperature and kidneys; followed by clearing heat, removing stasis, nourishing yin, and activating blood. There have also been reports of acupuncture, massage, acupoint injection, electrical stimulation, topical cakes and other methods of treatment, but the operation is very inconvenient, and patients often need to go to a qualified medical unit, or affect the patient's actions, which is to a large extent It has limited its clinical application. For diarrhea-type irritable bowel syndrome, it belongs to the category of "diarrhea". It is caused by liver qi stagnation, liver loss, liver stasis, and spleen. There are symptoms of liver stagnation and spleen deficiency, and the main treatments are to relieve liver stagnation and relieve spleen and strengthen spleen. Although the commonly used traditional Chinese medicine prescriptions such as Tongxie Yaofang, Shenling Baizhu Powder, Banxia Xiexin Decoction, Xiaoqinglong Decoction can be added and subtracted according to the symptoms, they are decoctions, which are very inconvenient in carrying and taking. The decoction process takes a long time, especially for patients with diarrhea. Because of the urgent symptoms, the disease is often delayed, and the taste is not good, and the patient's compliance is poor. In addition, if the decoction is given to the patient, it is not only inconvenient. , Also because of its improper operation and other reasons cause poor efficacy. In terms of proprietary Chinese medicines, Bupi Yichang Pills, Huoxiangzhengqi Water, Huoxiangzhengqi Liquid, Huoxiangzhengqi Soft Capsules, Huoxiangzhengqi Dropping Pills, etc. are commonly used, but these drugs are not mainly aimed at irritable bowel syndrome. The developed products are not very effective in treating the above-mentioned irritable bowel syndrome.

 Therefore, the present invention aims to provide a new Chinese medicine for treating irritable bowel syndrome, which has the advantages of strong pertinence, good curative effect, non-toxic side effects, and convenient taking and carrying. Summary of the invention

 The purpose of the present invention is to provide a new traditional Chinese medicine prescription for treating irritable bowel syndrome. The medicine has definite effect on diarrhea-type irritable bowel syndrome, has small side effects, good safety, and is convenient to take and carry.

 Another object of the present invention is to provide a new traditional Chinese medicine preparation prepared by the formula.

 Another object of the present invention is to provide a method for preparing the above-mentioned traditional Chinese medicine preparation.

 According to the traditional Chinese medicine formula of the present invention, the raw materials with the following weight ratios are provided: 1 part of peppermint oil and 80-180 parts of white peony / red peony.

 According to a preferred solution, the weight ratio of the drug substance contained in the Chinese herbal medicine formula of Shangmi is: 1 part of lutein oil and 100-160 parts of white peony / red peony. Further preferred weight ratio is: 1 part of peppermint oil and 130 parts of white peony / red peony.

 The Chinese medicinal preparation according to the present invention is obtained by mixing an extract obtained by treating white peony / red peony with a conventional extraction method and 1 part of peppermint oil.

 According to a preferred solution, the above extract is an extract powder obtained by water extraction and purification.

 The traditional Chinese medicine preparation according to the present invention is preferably a tablet, a hard gel liniment or a soft gel liniment.

The above-mentioned traditional Chinese medicine preparation for treating irritable bowel syndrome may also contain medicinal excipients required for preparing different dosage forms of medicines, such as lubricants such as magnesium stearate, talc, and polymer when preparing tablets or hard capsules. Glycols, etc., fillers such as starch, dextrin, sucrose, lactose, mannitol, calcium sulfate, etc., disintegrating agents such as microcrystalline cellulose, low-substituted hydroxypropyl cellulose, etc., binders such as Ethylcellulose, povidone, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, gelatin, ethanol, modified starch, etc. When preparing soft gel tinctures, various vegetable oils (such as soybean oil, tea oil, etc.) are added. , Peanut oil, etc.), lecithin, beeswax, glycerin, polyethylene glycol, propylene glycol, isopropyl alcohol, paraben ester series, etc. All the above excipients can be purchased from pharmaceutical excipient manufacturers.

 Paeonia lactiflora / paeonia lactiflora in the method for preparing a Chinese medicinal preparation according to the present invention can be extracted by conventional methods, for example, water extraction method, organic solvent extraction method, supercritical extraction method and the like.

 According to a preferred solution, the white peony / red peony is extracted and purified with water to obtain an extract powder. It includes the following steps:

(1) Extracting white peony / red peony: take the white peony or red peony medicinal materials in the proportion, add 6 to 10 times the amount of water to cook and extract 2-4 times, each time for 3 hours, filter, and filter the combined filtrate Concentrated to a relative density of about 1. 10-1. 20, adding 2-4 times the amount of an 80-95% ethanol solution, standing the precipitate for 12-48 hours, filtering, recovering the filtrate to ethanol and concentrating to a relative density of about 1. 10 -1. 20, add an equal amount of 0.2mol / L NaHC0 ₃ solution, stir to dissolve, add 3-5 times the amount of ethyl acetate to extract 2 to 4 times, combine the ethyl acetate extracts, and recover ethyl acetate to near Dry, then add 2-5 times the amount of 75-85% ethanol solution to dissolve, filter, then recover the filtrate to ethanol and concentrate to a relative density of about 1. 10- 1. 20, spray-dried to obtain white 芍 / Red 芍 dipping Powder

 (2) Preparation of preparations: Take the mentioned ratio of menthol oil and mix with the white scallion / red scallion extract powder prepared in step (1) to prepare various preparations according to conventional techniques.

 Among them, the content of paeoniflorin in the peony / red peony extract powder obtained in the above step (1) can reach more than 30% (g / g). In order to obtain Paeonia lactiflora / Red peony extract powder with higher paeoniflorin content, other methods can be used to further refine it.

 The dosage form of the Chinese medicine for treating irritable bowel syndrome is more preferably a soft gel tincture, which consists of a soft gel tin content containing the above-mentioned peppermint oil and white tincture / red tincture extract powder and a soft gel tin covering the surface The shell composition; and the contents of the soft gum tincture also contain any one or more medicinal excipients selected from vegetable oil, soybean phospholipids, beeswax, glycerin, polyethylene glycol, propylene glycol, and isopropanol; Contains gelatin, glycerin and water.

 The soft gelatin shell can also contain sorbic acid, acrylic resin II, acrylic resin III, water, titanium dioxide, sodium hydroxide, sucrose, ethyl paraben, paraben and propyl paraben. Any one or more.

 The preferred components of the above soft gum tincture: wherein the contents of the soft gum tincture contain the following weight ratio components: 1 part of peppermint oil, extract powder obtained from 100-160 parts of white tincture / red tincture, 1.5 -3 parts of soybean oil, 0.02-0.08 parts of soybean phospholipids, and 0.02-0.08 parts of beeswax; the components of the soft gelatin shell are: 3 parts gelatin, 1. 2-1. 8 parts glycerin, 0 · 6-1. 0 parts acrylic resin II, 0. 2- 0. 6 parts acrylic resin III, 0. 008- 0. 012 parts of paraben ethyl ester, 0. 18- 0. 24 parts sodium hydroxide, 2-3 parts of water.

The content of a further preferred soft gum tincture contains the following weight ratio components: 1 part of peppermint oil, extract powder obtained from 130 parts of white peony / red peony, 2.2 parts of soybean oil, 0.05 parts of soybeans Phospholipids and 0.05 Parts of beeswax; the components of the soft gum shell are: 3 parts of gelatin, 1.5 parts of glycerin, 0.8 parts of acrylic resin II, 0.4 parts of acrylic resin III, 0.01 parts of paraben ethyl ester, 0. 21 parts of sodium hydroxide, 2.5 parts of water.

 Preferably, an enteric film coating may be coated on the surface of the soft gelatin tincture to form an enteric soft gel tincture. The main ingredients of enteric film coatings are enteric coating materials, there are many reviews in the literature and reports, commonly used and necessary ingredients ^ "Enteric acrylic resins such as domestic I, II, III, respectively, are equivalent For imported Eudragit t L30D, L100D, S100, this kind of material does not dissolve in gastric juice, but dissolves into salt in intestinal fluid with higher pH value; among them, widely used are II, III (commonly used a certain proportion of their mixture ); In addition, some cellulose derivatives such as hydroxypropyl fluorenyl cellulose, ethyl cellulose, propyl cellulose, and polyvinylpyrrolidone can be optionally added. The above materials are commercially available.

 The preparation method of the traditional Chinese medicine soft tincture for treating irritable bowel syndrome includes the following steps:

(1) Extracting white scallion / red scallion: take the ratio of white scallion or scallion medicinal materials, add 6-10 times the amount of water to decoction and extract ^{2 to} 4 times, each time 1-3 hours, after ^, combine the filtrate And concentrated the filtrate to a relative density of about 1.10-1.20, added 2-4 times the amount of an 80-95% ethanol solution, left the precipitate for 12-48 hours, filtered, recovered the filtrate and concentrated the ethanol to a relative density About 1. 10- 1. 20, add equal amounts

0. 1- 0 · 3mol / L NaHC0 ₃ solution, stir to dissolve, add 3-5 times the amount of ethyl acetate to extract 2-4 times, combine the ethyl acetate extracts, recover ethyl acetate to near dry, then add 2 -5 times the amount of 75-85% ethanol solution to dissolve, filter, and then filter the filtrate back to ^! T ethanol and concentrate to a relative density of about 1. 10-1. 20, spray-dried, to obtain white tincture / red tincture extract powder ;

 (2) Preparation of soft gelatine contents: Take the soybean oil of the national ratio, heat it to 55-60 ° C, add the soybean phospholipid and beeswax in the ratio, and after dissolving and mixing, add the ratio of the Peppermint oil, mix well, add the white scallion / red scallion extract powder prepared in step (1) while stirring, and continue stirring for 20-60 minutes after the addition is complete, and then mix thoroughly with colloid mill, let stand for 8 Spare for more than an hour;

 (3) Preparation of soft film: first prepare a 3-10% sodium hydroxide solution for use; another appropriate amount of purified water is added, the acrylic resin II and acrylic resin III are added in the proportion, stirred for 20-60 minutes, and left to stand for 40- After 120 minutes, add the pre-prepared sodium hydroxide solution while stirring. After alkalizing for 40-100 minutes, transfer to a gelatinizer, heat to 80-85 ° C under stirring and keep for 30-60 minutes. Add the proportion of gelatin, glycerin and ethyl paraben, continue heating and stirring to completely dissolve the gelatin, keep it at 80-85 ° C for 30-60 minutes, and remove some water by vacuum to control the water content. At about 18-35%, go through a 80-mesh sieve and transfer it to a stable plastic barrel, and keep it at 55-60 ° C for more than 10 hours to obtain a glue solution; then make this glue solution according to the conventional process to make it thick. Soft film with uniform curtain and elasticity;

(4) Making a soft gelatin capsule: The contents of the soft gelatin capsule and the soft gelatin capsule press on the soft film are pressed into a soft gelatin capsule of a certain specification. Wherein, the content of paeoniflorin in the Paeonia lactiflora / Red paeonia extract powder prepared in the above step (1) can reach more than 30% (g / g). In order to obtain the peony / red peony extract powder with higher paeoniflorin content, it can be further refined by other methods.

 If necessary, an enteric-type film coating can also be coated on the surface of the soft gelatin capsules prepared above according to a conventional coating process to form an enteric soft gelatin capsule.

The menthol oil mentioned in the present invention is a volatile oil obtained from fresh stems or leaves of Labiatae mint (Mentha haplocalyx Bi-iq.) After being steam-steamed, frozen, and partially de-brained, namely Chinese Pharmacopoeia 2000 A contained mint oil. Its quality should comply with Chinese Pharmacopoeia standards: the total alcohol content is calculated according to menthol (d. H _2.0 ), and it should not be less than 50.0% (g / g).

 Peppermint oil can be purchased from legal API manufacturers, or it can be prepared from the Chinese herbal medicine peppermint according to the method described above.

In the present invention, the white peony / red peony refers to white peony, red peony, or a mixture of white peony and red peony. The Paeonia lactiflora referred to in the present invention is processed from the roots of Paeonia lactiflora Pall., And the processing method is as follows: after removing the head and tail and the fibrous roots, scrape off the skin, and cook in boiling water until thoroughly Remove the heart, soak it in cold water, and take it out for drying (or cook it first, then scrape the skin, and then dry it); The red scallion mentioned in the present invention is Paeonia lactiflora Pall. Or Sichuan red Dried root of Paeonia (Paeonia veitchii Lynch.). The 2000 edition of the Pharmacopoeia of the People's Republic of China contains paeonia lactiflora and paeonia lactiflora, both of which are mainly paeoniflorin, and their quality should meet the national standards. Among them: Paeonia lactiflora (C i U must not be less than 0.80% (g / g), paeoniflorin (C ₂₃ H _2S 0 _u ) in red peony must not be less than 1.80% (g / g).

Compared with the prior art, the beneficial effects of the present invention are: (1). In the prior art, there is no Chinese medicine that is the same as the traditional Chinese medicine prescription of the present invention, and there is no targeted treatment for irritable bowel syndrome. Chinese patent medicine, the invention uses for the first time a scientific formula of peppermint oil and paeonia lactiflora / red peony as a raw material medicine, and is composed of a certain weight ratio. It has been proven by animal tests and clinical trials to have liver relieving depression, analgesic and anti-inflammatory properties. The effects such as regulating qi and stopping diarrhea are used for prevention and treatment of diarrhea-type irritable bowel syndrome, and the effect is precise; especially the optimized formula has particularly excellent effect. (2) Compared with chemical medicines: The menthol oil and paeonia lactiflora and radix paeoniae in the medicine of the present invention are commonly used traditional Chinese medicines, and have been proven by pharmacological and toxicological tests to have small toxic and side effects, good safety, and low cost. The cost of treatment is low. (3) Compared with traditional decoctions, pills, etc., in the preparation process of the drug of the present invention, a reasonable extraction process is used to process the peony / red chrysanthemum material in the drug substance, and the effective ingredients can be fully extracted, and It can reduce impurities and increase the content of active ingredients. After taking the preparation, the dosage is small. It only needs to take 2 tablets or 2 capsules at a time. It is easy for patients to accept and can improve patient compliance to a certain extent. In addition, it is convenient to take and carry after making a suitable preparation. Menthol oil mainly contains menthol (Menthol, 40-60%), menthol (Menthone) and other ingredients: It has the effects of expelling wind, regulating qi, depressing, anti-inflammatory, analgesic, etc. It has the effects of excitement, anti-vomiting and anti-depression. The main components of Paeonia lactiflora and Paeonia lactiflora are Paeoniflorin, which have good effects of dilating blood vessels, analgesic and sedative, anti-inflammatory and anti-ulcer, antipyretic and spasm, and diuretic. Small, with good safety and tolerance. The medicament of the present invention combines peppermint oil with paeonia lactiflora and paeonia lactiflora in a scientific combination, and plays a role in relieving liver and stagnation, analgesic and anti-inflammatory, and regulating qi and diarrhea.

 In order to confirm the efficacy of the drug of the present invention, a better plan was screened, and the safety of the drug of the present invention was also examined to provide a theoretical basis for clinical use. The inventors conducted animal pharmacodynamic pre-tests, animal acute toxicity tests and clinical treatments. The tests and other inspections adopted the following methods and test results:

 I. Pre-examination of animal pharmacodynamics (Effect of the drug of the present invention on diarrhea model of irritable bowel syndrome in rats)

 Experimental material

 1.1 Drugs

 The medicament of the present invention made with different drug substance ratios is homemade and diluted with edible oil. The positive control drug Yimengling (Luobutamide hydrochloride) was a product of Xi'an Yangsen Pharmaceutical Co., Ltd.

 1.2 Animals

 Sixty-four SD rats, male, weighing 180 ± 20 g, were purchased from the Laboratory Animal Research Institute of the Chinese Academy of Medical Sciences.

 Experimental method

 2.1 Grouping of animals

 The rats were randomly divided into 8 groups of 8 rats each, namely the blank control group (injected with edible oil Iml / lOOg), the positive drug group (2 mg / kg Yimeng stop), peppermint oil, and peony / red The composition ratio of the drug substance is 1: 100 (white peony), 1: 130 (white peony), 1: 160 (white peony), 1: 130 (red peony). There are four experimental groups (groups 1 to 4). A peppermint oil group (笫 5 group) and a white） group (笫 6 group are prepared according to the method for extracting white 芍 / red 芍 in the present invention). 10 times of the intended clinical dose was administered orally once a day for 6 consecutive days. One hour after the daily administration, a diarrhea model of irritable bowel syndrome (IBS) in rats with restraint stress was made. See Table 1:

 Table 1 Grouping of animals and dosage

 Group Peppermint oil (g / kg) Paeonia lactiflora / Red peony (raw medicine, g / kg) Blank (edible oil) 0 0

 Positive drug (easy to stop) 0 0

 1 0.1 10 (white pheasant)

2 0.1 13 (white pheasant)

3 0.1 16 (white lotus) 4 0.1 13 (Chiba)

 5 0.1 0

 6 0 20 (white 芍)

2.2 Model of irritable bowel syndrome (IBS) diarrhea in rats with restraint stress

 SD rats of each group were dosed daily after administration, and the castor oil was 0.1 g / 100 g, and both hind limbs were restrained, which made it difficult to move, irritable, and caused certain stress stimulation. After making the model in this way for 6 consecutive days, the rats were placed in metabolic cages with filter paper, and the absorbent paper was changed once an hour. The defecation latency, diarrhea rate, and loose stool rate were recorded.

 3. Experimental results

 Each group of the medicine of the present invention can significantly prolong the incubation period of diarrhea caused by castor oil in rats, significantly reduce the cumulative number of diarrhea, and the effect can be maintained to a minimum of 2 hours after the medicine; the effect of reducing the loose stool rate can be maintained to 6 hours after the medicine. Compared with the blank group, the difference is significant (P <0.05). The results are shown in Tables 2 and 3.

 Table 2 Effects on castor oil-induced diarrhea in rats (1) (= ^; x 土 s)

 Diarrhea incubation period

 Group

 (min) lh 2h 6h

 Blank 23.3 ± 11.7 3.1 ± 1.5 5.6 ± 2.1 6.7 ± 2.4 Easy to stop 58.2 ± 30.4 * 1.4 ± 1.2 * 2.9 ± 1.9 ^ ^ 4.3 ± 2.1 *

1 45.9 ± 29.1 * 1.5 ± 0.5 * 3.4 ± 2. ^ 4.6 ± 2.7 *

2 53.9 ± 24.1 ** 1.5 ± 0.5 * 3.4 ± 2. In ^ 5.2 ± 2.7 *

3 52.6 ± 22.0 ** 1.6 ± 1.5 * 3.7 ± 2.5 ^ ^ 5.0 ± 3.1 *

4 52.1 ± 23.2 ** 1.5 ± 0.4 * 3.6 ± 2.2 ^ ^ 4.1 ± 1.9 *

5 48.9 ± 19.1 * 1.7 ± 0.5 * 4.0 ± 2.1 ^ ^ 6.0 ± 3.7

6 45.6 ± 28.0 * 1.6 ± 1.5 * 4.3 ± 2.5 * 5.0 ± 3.1

 Note: * Comparison with blank group P <0.05 ** Comparison with blank group P <0.01

 Table 3 Effects on castor oil-induced diarrhea in rats (2) (n = 8; x "± s)

 Cumulative thin stool rate

 Group

 lh 2h 6h

 Blank 0.39 ± 0.15 0.59 ± 0.19 0.61 ± 0.18

 Yimeng stop 0.18 ± 0.14 ** 0.29 ± 0.13 ** 0.39 ± 0.14 *

 1 0.33 ± 0.18 0.38 ± 0.30 * 0.38 ± 0.27 *

2 0.27 ± 0.34 * 0.40 ± 0.40 * 0.41 ± 0.27 *

3 0.18 ± 0.23 ** 0.30 ± 0.26 ** 0.36 ± 0.25 **

4 0.25 ± 0.19 * 0.32 ± 0.21 ** 0.42 ± 0.22 *

5 0.26 ± 0.18 * 0.46 ± 0.30 * 0.46 ± 0 · 27 *

6 0.30 ± 0.34 0.60 ± 0.40 0.60 ± 0.27 Note: Compared with the blank group "^ P <0.05 ** Compared with the blank group P <0.01

4 Conclusion

The medicine of the present invention has an inhibitory effect on diarrhea model of irritable bowel syndrome in rats caused by castor oil, The effect of peppermint oil alone or paeony is better, and it is equivalent to that of the positive control drug Yimeng stop, suggesting that this product has a good effect in treating irritable bowel syndrome.

 Second, animal safety test investigation

 In order to study the safety of the drug of the present invention and provide a theoretical basis for clinical use, the inventor conducted an investigation on the acute toxicity test and the like. The test results are as follows:

The toxicity of peppermint oil is very low, and LD ₅ cannot be detected when given by gavage. The maximum tolerated amount is greater than 4000 mg / kg, which is more than 670 times the usual clinical dose in humans; LD ₅ when intraperitoneally injected. = 1144. 9

78. 5mg / kg.

 Both white peony and red peony are traditionally used in traditional Chinese medicine, and their toxicity and obvious side effects have not been found in thousands of years of practice. Acute toxicology research in modern medicine shows that it is safe for oral administration.

The results of pharmacological and toxicological tests are: LD _{5 of} mice by intravenous injection and intraperitoneal injection of Paeonia lactiflora extract (prepared according to the method of extracting Paeonia lactiflora / Red paeony in the preparation method of the present invention, the same applies hereinafter). 159mg / kg (equivalent to approximately 12.2g / kg of raw medicinal materials) and 230mg / kg (equivalent to approximately of raw medicinal materials)

17. 7g / kg); Feeding mice with paeony extract about 3000 mg / kg (equivalent to about 230g / kg of raw medicinal materials), no obvious symptoms of poisoning and no death. The results of chronic toxicology studies showed that: it has no obvious toxicity to important organs of mice. Rats and dogs were given 3 different doses of Paeonia lactiflora extract (50 mg / kg, 1,000 mg / kg, 2000 mg / kg per day, equivalent to 5 to 200 times the highest adult dose) for 30 and 90 days. No obvious toxic damage, indicating that the drug has low toxicity and a large safety range. All three tests were negative; in the study of Paplin's reproductive toxicity test (teratogenic fetal test), when the dosage was as high as 2160mg / kg, there was still no teratogenic effect on the survival, appearance, tissue and organ development, bones of fetal rats. There was no significant effect on development. In addition, Amaranth is often used for abortion in Chinese medicine, so it is suggested that Amaranth may also be suitable for pregnant patients, and its safety is more reliable.

 Red peony (extract prepared according to the method for extracting white peony / red peony in the medicine preparation method of the present invention) The maximum tolerated amount for intravenous injection in mice is greater than 50g / kg (raw medicine), and the maximum tolerated for mice by intragastric administration The amount is greater than 280 g / kg (raw herbs).

Oral gavage of the drug of the present invention (based on the drug substance peppermint oil: paeony ratio of 1: 130). Mice were gavage LD ₅ "= 8670mg / kg, which is about 300 times the commonly used clinical dose in humans.

 The above toxicity test results suggest that the drug of the present invention has less toxic side effects and high safety.

 Clinical observation of the drug of the present invention in treating irritable bowel syndrome

 1. Clinical information

 1.1 Case selection criteria

 1. 1. 1 diagnostic criteria for irritable bowel syndrome (diarrhea type)

Formulated with reference to the clinical diagnostic reference standards of the National Symposium on Chronic Diarrhea in 1986: (1) Abdominal pain, bloating, diarrhea for more than two years, with systemic neurosis ^

(2) The general condition is good, no wasting and fever, and only a tenderness in the abdomen was found on the physical examination.

 (3) Negative fecal routine and culture (at least three times) were negative, and fecal occult blood test was negative.

 (4) X-ray barium enema examination showed no positive findings or irritation of the colon.

 (5) Fiber colonoscopy is normal, some patients have hyperkinesia, increased mucus, no obvious mucosal abnormalities, and histological examination is basically normal.

 (6) blood and urine are normal and erythrocyte sedimentation is normal

 (7) There is no history of parasites such as dysentery and schistosomiasis, and the test treatment is invalid.

 1.1.2 Case inclusion criteria

 (1) Meet the diagnostic criteria for irritable bowel syndrome (diarrhea type).

 (2) Male or female aged 18-60 years.

 1.1.3 Case exclusion criteria

 (1) Organic intestinal diseases (tumor, inflammation, congenital abnormalities, malabsorption syndrome, etc.).

 (2) Those under the age of 18 or over 60 years, pregnant or lactating women, a history of drug allergies or allergies.

 (3) Patients with severe primary diseases such as heart, brain, liver, kidney and hematopoietic system, and psychiatric diseases.

 (4) Those who have received relevant treatment within two weeks may affect the judgement of curative effect.

 (5) Those who cannot use the drug according to the regulations, do not meet the inclusion criteria, cannot determine the curative effect, or have incomplete materials will affect the curative effect or safety determination.

 (6) Participants in other clinical trials.

 1, 2 general information

 All cases were from outpatient or inpatient cases from January 2003 to November 2003. According to the order of consultation, they were randomly divided into treatment group and control group. Among the 20 patients in the treatment group, 11 were males and 9 were females. The maximum age was 43 years and the minimum age was 25 years, with an average of 35.51 years. 3.27 ± 1.36 years. Among the 20 cases in the control group, there were 8 males and 12 females; the oldest was 45 years old and the youngest was 23 years old, with an average of 36.96 years. The course of disease was 2.2 years to 5.5 years, with an average of 3.85 ± 1.03 years. There were no significant differences in the age, gender, and medical history of the two groups of patients, which were comparable.

 2. Treatment methods

 Using the double-blind and double-simulation method, the treatment group was administered the drug of the present invention (the raw drug composition of the drug is: 100g of peppermint oil, 13000g of white peony, 220g of soybean oil, 5g of soybean phospholipid, 5g of beeswax, and 1000 soft capsules were made) Oral, 3 times a day, 2 capsules / time; the control group was given an equal dose of soft gelatin made of monomenthol oil, orally, 3 times a day, 2 capsules / time, the course of treatment was 1 month.

3. Efficacy Evaluation Standards Symptom grading criteria (see Table 4) were used.

 Symptom grading scale

 The total score of symptoms before and after treatment (addition of each symptom score) was recorded, and the effect ratio was used to evaluate the effect.

 Points ratio = points before treatment-points after treatment X 100%

 Pre-treatment points

 (1) Clinical cure: The symptoms disappeared, and no recurrence was observed and followed for two weeks.

 (2) Significantly improved clinical symptoms, symptom score ratio> 70%

(3) Effective: clinical symptoms improved, symptom score ratio> 30%, <70% ₀

 (4) Ineffective: No obvious improvement in clinical symptoms, or even exacerbation, symptom score ratio <30%

 4.Treatment results (see Table 5)

 Comparison of the efficacy of the two groups after treatment

Group-n clinical cure (° /.) Markedly effective (%) effective (%) ineffective (%) total effective rate (%) treatment group 20 2 (10) 8 (40) 1 (5) 95 control group 20 0 7 (35) 7 (35) 6 (30) 70

Note: The statistical comparison of the total effective rate between the two groups was P <0.01, which was significant. Conclusion: From the above results, the present invention is the pharmaceutical treatment of irritable bowel syndrome (diarrhea type) of the total effective rate was ^95% efficacy alone and peppermint oil has a significant statistical difference compared. It shows that the medicine of the present invention has obvious therapeutic effect on irritable bowel syndrome (diarrhea type). detailed description

 The present invention is described in further detail below in conjunction with specific embodiments.

Example one This embodiment is a hard gum tincture, and the raw material components of the contents of the gum tincture are: 1 part of peppermint oil and 130 parts of white tincture.

 Make a hard gel tincture by a method that includes the following steps:

(1) Extracting Paeonia lactiflora: Take the medicinal materials of Paeonia lactiflora and add 10 times the amount of water to decoction and extract 4 times for 2 hours each time, filter, combine the filtrates, and concentrate the filtrates to a relative density of about 1.10, add 2 An 80% ethanol solution was doubled, and the precipitate was left standing for 12 hours, filtered, and the filtrate was recovered to ethanol and concentrated to a density of about 1.10. Add an equal amount of a 0.2mol / L NaHC0 ₃ solution, stir to dissolve, and add 34 ， Extract twice with ethyl acetate, combine the ethyl acetate extracts, recover the ethyl acetate to near dryness, add about 2 times the 85% ethanol solution to dissolve, filter, and then recover the filtrate to ethanol and concentrate to a relative density of 1.10. Spray-dried to obtain white tincture extract powder;

 (2) Formulation: Take the blended mint oil and mix it with the white tincture extract powder prepared in step (1), put it into the capsule shell, and make 0.5g / grain hard capsule, that is, can.

 Example two

 This example is an enteric hard gelatin tincture. The raw material ingredients of the gelatin capsule are: 1 part of peppermint oil, 160 parts of white tincture, and 0.01 part of magnesium stearate.

 An enteric hard gel tincture is prepared by a method that includes the following steps:

(1) Extracting Paeonia lactiflora: Take the ratio of Paeonia lactiflora and add 6 times the amount of water to decoction to extract 3 Huan, each 3 hours, filter, combine the filtrate, and concentrate the filtrate to a relative density of about 1.20, add 4 Double the amount of 95% ethanol solution, leave it to stand for 48 hours, and filter. The filtrate is recovered and concentrated to a mesh density of about 1.20. An equal amount of 0.2mol / L NaHC0 ₃ solution is added. Stir to dissolve. Add 5 times the amount. Extracted 4 times with ethyl acetate, combined the ethyl acetate extracts, recovered ethyl acetate to near dryness, and added 2 times the amount of 85% ethanol solution to dissolve, filtered, and then recovered the filtrate to ethanol and concentrated to a relative density of about 1.20, Spray-dried to obtain white tincture extract powder;

 (2) Preparation: take the mentioned ratio of menthin oil and magnesium stearate, mix it with the white tincture extract powder prepared in step (1), and put it into the intestine tin shell to make 0.5g / grain Of hard gelatin, just fine.

 Example three

 This embodiment is an enteric hard gelatin tincture. The raw material ingredients of the gelatin capsule are: 1 part of mint t oil and 80 parts of red tincture.

 An enteric hard gel tincture is prepared by a method that includes the following steps:

(1) Extracting red scallion: Take the red scallion medicinal materials with the proportion and add 8 times the amount of water to cook and extract 2: twice for 1 hour each time, filter, combine the filtrates, and concentrate the filtrates to a relative density of about 1.15, add 3 times the amount of 85% ethanol solution, left standing for 16 hours, filtered, the filtrate was recovered ethanol and concentrated to a mesh density of about 1.15, the same amount of 0.2mol / L NaHC0 ₃ solution was added, stirred to dissolve, added 4 times the amount Extract 3 times with ethyl acetate, combine the ethyl acetate extracts, recover the ethyl acetate to near dryness, add 5 times the amount of 75% ethanol solution to dissolve, filter, then recover the filtrate to ethanol and concentrate to a relative density of about 1.10, spray Dried to obtain red chrysalis extract powder;

 (2) Formulation: take the mentioned ratio of menthol oil, mix it with the red chrysanthemum extract powder prepared in step (1), and put it into the intestine husk to make 0.5 g / capsule of hard gelatine. Just fine.

 Example 4

 This embodiment is a film-coated tablet, and the raw material components of the core are: 1 part of peppermint oil, 180 parts of white peony, and 5 parts of corn starch.

 Tablets are made by a method that includes the following steps:

(1) Extracting Paeonia lactiflora: Take the medicinal materials of Paeonia lactiflora and add 7 times the amount of water to decoction and extract 3 times, 3 hours for the first time, 1.5 hours for the second and third times, filter, combine the filtrates, and The filtrate was concentrated to a relative density of about 1.15, 3 times the amount of a 90% ethanol solution was added, and the precipitate was left to stand for 18 hours, filtered, the filtrate was recovered to ethanol and concentrated to a relative density of about 1.15, and an equal amount of a 0.2mol / L NaHC0 ₃ solution was added. , Stir to dissolve, add 4 times the amount of ethyl acetate and extract 3 times, combine the ethyl acetate extracts, recover the ethyl acetate to near dry, then add 4 times the amount of 80% ethanol solution to dissolve, filter, and then recover the filtrate Ethanol and concentrated to a relative density of about 1.15, spray-dried to obtain white tincture extract powder;

 (2) Preparation: Take the mentioned ratio of peppermint oil and corn starch, mix with the Paeonia lactiflora powder obtained in step (1), uniformly press into a 0.5g / tablet core according to the conventional process, and then The surface of the tablet core is covered with a film coating.

 Example 5

 This embodiment is an enteric film-coated tablet. The raw material components of the tablet core are: 1 part of peppermint oil and 100 parts of red pepper.

 Tablets are made by a method that includes the following steps:

(1) Extracting red scallion: Take the red scallion medicinal materials with the proportion, add 9 times the amount of water to cook and extract twice, 1.5 hours each time, filter, combine the filtrates, and concentrate the filtrates to a relative density of about 1.18, add 4 90% ethanol solution, settle for 24 hours, and filter. The filtrate was recovered and concentrated to a relative density of about 1.15. An equal amount of 0.2mol / L NaHC0 ₃ solution was added, stirred to dissolve, and 5 times the amount of acetic acid was added. Extract twice with ethyl acetate, combine the ethyl acetate extracts, recover the ethyl acetate to near dryness, add 3 times the amount of 80% ethanol solution to dissolve, filter, and then recover the filtrate to ethanol and concentrate to a relative density of about 1.15, spray-dried To get red chrysanthemum extract powder;

(2) Formulation: Take the mentioned ratio of menthol oil, mix with the red chrysanthemum extract powder obtained in step (1), uniformly press into a tablet core of 0.5 g / tablet according to the conventional process, and then place it on the surface of the tablet core. Cover with an enteric film coating. Embodiment 6

 This embodiment is a soft gel tincture, where:

 The drug substance components of the contents of the soft gum tincture are: 1 part of peppermint oil, 150 parts of white tincture, and 2.6 parts of tea oil. The soft film is composed of the following weight ratio components: 3 parts of gelatin, 1 part of glycerin, 0.09 part of paraben, 1.6 parts of water.

 Make a soft gel tincture by a method that includes the following steps:

(1) Extraction of Paeonia lactiflora: Take the medicinal materials of Paeonia lactiflora and add 8 times the amount of water to decoction and extract 3 times, 2.5 hours each time, filter, combine the filtrates, and concentrate the filtrates to a relative density of about 1. 10, add 2 times the amount of 95 ° /. The ethanol solution was left standing for 30 hours, filtered, and the filtrate was recovered and concentrated to a relative density of about 1.18. An equal amount of a 0.2mol / L NaHC0 ₃ solution was added, stirred to dissolve, and 3 times the amount of ethyl acetate was added. Ester extraction 4 times, combined ethyl acetate extracts, recovered ethyl acetate to near dryness, then added 3 times the amount of 80% ethanol solution to dissolve, filtered, and then recovered the filtrate to ethanol and concentrated to a relative density of 1.15, spray Dried to obtain white tincture extract powder;

 (2) Preparation of soft gelatin content: Take the proportion of tea oil, heat to about 58 ° C, add the proportion of menthol oil, mix well, and add the prepared in step (1) while stirring. Paeonia lactiflora powder, continue to stir for 1 hour until the addition is complete, so that the mixture is uniform, and then colloid mill to make further mixing, let it stand for more than 10 hours;

 (3) Preparation of soft film: Take an appropriate amount of purified water, add the ratio of gelatin, glycerin and nipaginate, heat and stir to completely dissolve the gelatin, keep it at 30 ° C for 30 minutes, and remove some water by vacuum Control the moisture in it to about 29%. After passing through 80 mesh sieve, transfer it to a stable plastic barrel, and keep it at 55-60 ° C for more than 12 hours to obtain a glue solution. Then, use this glue solution as usual. Process to make soft film with uniform thickness and certain elasticity for future use;

 (4) Making soft gelatin capsules: press the soft gelatin capsules into the contents of the soft gelatin capsules and press the soft gelatin capsules into 0.1 soft gelatin capsules.

 Example Seven

 This embodiment is a soft gel tincture, where:

 The drug substance components of the contents of the soft capsules are: 1 part of peppermint oil, 140 parts of peony, 2.4 parts of soybean oil, 0.07 parts of soybean phospholipids, and 0.03 parts of beeswax.

 The soft film is composed of the following weight ratio components: 3 parts gelatin, 1.5 parts glycerin, 1 part water. Make a soft gel tincture by a method that includes the following steps:

(1) Extracting white peony: take the ratio of white peony, add 10 times the amount of water to cook and extract 4 times, 2 hours each time, filter, combine the filtrate, and concentrate the filtrate to a relative density of about 1. 20, 3 times the amount of 85% ethanol solution was added, and the precipitate was allowed to stand for 36 hours, filtered, and the filtrate was recovered into ethanol and concentrated to a relative amount. Density is about 1.12, add an equal amount of 0.2mol / L NaHC0 ₃ solution, stir to dissolve, add 5 times the amount of ethyl acetate to extract twice, combine the ethyl acetate extracts, recover the ethyl acetate to near dry, and then add 2 times The amount of 85% ethanol solution was dissolved, filtered, and then the filtrate was recovered ethanol and concentrated to a relative density of about 1.18, and spray-dried to obtain Baiji extract powder;

 (2) Preparation of soft gelatin content: Take the soybean oil with the ratio, heat it to about 60 ° C, add the soybean phospholipid and beeswax in the ratio, and after dissolving and mixing, add the ratio Menthol oil, mix well, add the white peony extract powder obtained in step (1) while stirring, and continue stirring for 20 minutes after the addition is complete, and then mix evenly with colloid mill. Let stand 8 Spare for more than an hour;

 (3) Preparation of soft film: Take an appropriate amount of purified water, add the gelatin and glycerin in the proportion, heat and stir to completely dissolve the gelatin, keep it at 30 ° C for 30 minutes, and remove some water by vacuum to make the water in it. Controlled at about 18%, after passing through 80 mesh sieve, it was transferred to a stable plastic bucket, and kept at 55-60 ° C for more than 12 hours to obtain a glue solution. Then the glue solution was made into a uniform thickness according to a conventional process. And a flexible film with a certain elasticity is reserved;

 (4) Making soft gelatin capsules: The contents of the soft gelatin capsules and the soft gelatin capsule press on the soft film are pressed into a soft gelatin capsule of 0.5 g / grain, and then the process is completed.

 Example eight

 This embodiment is a soft gel tincture, where:

 The drug substance components of the contents of the soft capsules are: 1 part of peppermint oil, 130 parts of peony, 2.2 parts of soybean oil, 0.05 parts of soybean phospholipids, and 0.05 parts of beeswax.

 The soft film is composed of the following weight ratio components: 3 parts of gelatin, 1.5 parts of glycerin, 0.8 parts of acrylic resin II, 0.4 parts of acrylic resin III, 0.01 parts of paraben ethyl ester, 0.21 parts of sodium hydroxide, 2.5 parts of water.

 Make a soft gel tincture by a method that includes the following steps:

(1) Extracting Paeonia lactiflora: Take the medicinal materials of Paeonia lactiflora and add 8 times the amount of water to decoction and extract it twice, the first time is 2 hours, and the second time is 1 hour. Filter, combine the filtrates, and concentrate the filtrates to The relative density is about 1, 15, 3 times the amount of 85% ethanol solution is added, the precipitate is left for 16 hours, filtered, the filtrate is recovered ethanol and concentrated to a relative density of about 1.15, and an equal amount of a 0.2mol / L NaHC0 ₃ solution is added. Stir to dissolve, add 4 times the amount of ethyl acetate and extract 3 times, combine the ethyl acetate extracts, recover the ethyl acetate to near dry, add 3 times the amount of 80% ethanol solution to dissolve, filter, and then recover the filtrate by ethanol. Concentrated to a relative density of about 1.15, spray-dried to obtain Baiji extract powder;

(2) Preparation of soft gelatin content: Take the proportion of soybean oil, heat it to about 55 ° C, add the proportion of soybean phospholipid and beeswax, dissolve and mix, and add the proportion of Peppermint oil, mix well, add the white peony extract powder obtained in step (1) while stirring, and continue stirring until the addition is complete. Minutes, make the mixture uniform, and then colloid mill to further mix, let stand for more than 12 hours;

(3) Preparation of soft film: first prepare about 6.5% (g / g) sodium hydroxide solution for use; another appropriate amount of purified water is added, the acrylic resin II and acrylic resin III are added in the proportion, and stirred for 30 minutes, Allow to stand for 1 hour, and then add the pre-prepared sodium hydroxide solution while stirring. After alkalizing for 1 hour, transfer to a gelatinizer, heat to about 80Ό under stirring and keep for 45 minutes, then add the proportion Gelatin, glycerin, and ethyl paraben, continue to heat and stir to completely dissolve the gelatin, keep it at 80 ° C for 30 minutes, and remove some of the water by vacuum to control the moisture in it to about 30%. After sieving, it is transferred to a stable plastic barrel, which is kept under the condition of 55-60 ° C for more than 12 hours to obtain a glue solution. Then the glue solution is made into a thick and thin flexible film with a certain elasticity according to conventional processes for use;

 (4) Making soft gelatin capsules: The contents of the soft gelatin capsules and the soft gelatin capsules on the soft film are pressed into a soft gelatin capsule of 0.5 g / capsule.

 Example Nine

 This embodiment is a soft gel tincture, where:

 The drug substance components of the contents of the soft capsule are: 1 part of peppermint oil, 100 parts of red pepper, 2.4 parts of soybean oil, 0.07 parts of soybean phospholipid, and 0.03 parts of beeswax.

 The soft film is composed of the following weight ratio components: 3 parts of gelatin, 1.8 parts of glycerin, 0.9 parts of acrylic resin II, 0.5 parts of acrylic resin III, 0.09 parts of paraben ethyl ester, 0. 20 parts sodium hydroxide, 2.6 parts water.

 Make a soft gel tincture by a method that includes the following steps:

(1) Extracting red scallion: take the ratio of red scallion medicinal materials, add 6 times the amount of water to cook and extract 4 times, 1.5 hours each time, filter, combine the filtrates, and concentrate the filtrate to a relative density of about 1. 12, add 4 times the amount of 80% ethanol solution, leave the precipitate for 12 hours, filter, recover the filtrate and concentrate the ethanol to a relative density of about 1. 10, add an equal amount of 0.2mol / L NaHC0 ₃ solution, stir to make was dissolved, was added 5 volumes of ethyl acetate and extracted twice with ethyl acetate extracts were combined, ethyl acetate recovered to near dryness, then added 4-fold amount of ^75% ethanol solution to dissolve, filtered, then the filtrate was concentrated and recovering ethanol To a relative density of about 1.20, spray-dried to obtain red chrysanthemum extract powder;

 (2) Preparation of the contents of soft gelatine: Take the soybean oil with the ratio, heat it to about 60 ° C, add the soybean phospholipid and beeswax in the ratio, and after dissolving and mixing, add the ratio Menthol oil, mix well, add the red chrysanthemum extract prepared in step (1) for 4 minutes while stirring, and continue stirring for 20 minutes until the addition is complete, and then mix evenly with colloid mill. Let stand 8 Spare for more than an hour;

(3) Preparation of soft film: first prepare about 10% (g / g) sodium hydroxide solution for use; another appropriate amount of purified water is added, the acrylic resin II and acrylic resin III are added in the proportion, stirred for 20 minutes, and left to stand 2 hours, add the pre-prepared sodium hydroxide solution while stirring, turn to gel after 100 minutes of alkalization In a chemical pot, heat to about 82 ° C with stirring for 30 minutes, add the gelatin, glycerin, and paraben ethyl ester in the ratio, continue to heat and stir to completely dissolve the gelatin, at 82 ° C Incubate for 45 minutes, vacuum remove part of the water, control the moisture content to about 29%, and then transfer it to a stable plastic bucket after passing through an 80 mesh sieve. Keep it at 55-60 ° C for more than 10 hours to obtain the glue. This glue is then made into a soft film with a uniform thickness and a certain elasticity according to the conventional process for later use;

 (4) Making soft gelatin capsules: The contents of the soft gelatin capsules and the soft gelatin capsules on the soft film are pressed into a soft gelatin capsule of 0.5 g / capsule.

 Example 10

 This embodiment is a soft gel tincture, where:

 The drug substance components of the contents of the soft capsule are: 1 part of peppermint oil, 160 parts of peony, 3 parts of soybean oil, 0.02 parts of soybean phospholipid, and 0.02 parts of beeswax.

 The soft film is composed of the following weight ratio components: 3 parts of gelatin, 2.4 parts of glycerin, 0.6 parts of acrylic resin II, 0.3 parts of acrylic resin III, 0.008 parts of paraben propyl, 0. 24 parts of sodium hydroxide, 2.4 parts of water.

 Make a soft gel tincture by a method that includes the following steps:

(1) Extraction of Paeonia lactiflora: take the medicinal materials of Paeonia lactiflora, add 10 times the amount of water to decoction and extract 3 times, each time for 2 hours, filter, combine the filtrates, and concentrate the filtrates to a relative density of about 1.18, Add 3 times the amount of 90% ethanol solution, leave the precipitate for 24 hours, filter, recover the filtrate and concentrate the ethanol to a relative density of about 1.18, add an equal amount of 0.2mol / L NaHC0 ₃ solution, stir to dissolve, Add 3 times the amount of ethyl acetate for extraction 4 times, combine the ethyl acetate extracts, recover the ethyl acetate to near dry, then add 4 times the amount of 75% ethanol solution to dissolve, filter, then recover the filtrate to ethanol and concentrate to relative density For 1. 20, spray-dried to obtain white tincture extract powder;

 (2) Preparation of soft gelatine contents: Take the proportion of soybean oil, heat it to about 56 Ό, add the proportion of soybean phospholipids and beeswax, dissolve and mix, and add the proportion of mint The vegetable oil is mixed well, and the white peony extract powder prepared in step (1) is added while stirring. Continue stirring for 60 minutes until the addition is complete, and then mix evenly with colloid mill. Let stand for more than 12 hours. Spare

(3) Preparation of soft film: first prepare about 3% (g / g) sodium hydroxide solution for use; another appropriate amount of purified water is added, the acrylic resin II and acrylic resin III are added in the proportion, stirred for 60 minutes, and left to stand 1. 5 hours, add the pre-prepared sodium hydroxide solution while stirring, reduce to 40 minutes, transfer to a gelatinizer, heat to about 83 ° C and keep it for 1 hour under stirring, then add the Proportion of gelatin, glycerin and propyl paraben. Continue heating and stirring to completely dissolve the gelatin, keep it at 83 ° C for 1 hour, and remove some of the water by vacuum to control the moisture in it to about 27%. After 80 mesh sieve, it is transferred to a stable plastic barrel, and it is kept at 55-60 ° C for more than 10 hours, and then the monthly liquid is obtained; This glue solution is made into a soft film with uniform thickness and certain elasticity according to the conventional process.

(4) Making soft gelatin capsules: The contents of the soft gelatin capsules and the soft gelatin capsules on the soft film are pressed into a soft gelatin capsule of 0.5 g / capsule.

 Example 11

 This embodiment is a soft gel tincture, where:

 The drug substance components of the contents of the soft capsule are: 1 part of peppermint oil, 120 parts of peony, 2 parts of soybean oil, 0.03 parts of soybean phospholipid, and 0.08 parts of beeswax.

 The soft film is composed of the following weight ratio components: 3 parts of gelatin, 0.8 parts of glycerin, 0.7 parts of acrylic resin II, 0.6 parts of acrylic resin III, 0.011 parts of paraben ethyl ester, 0. 18 parts of sodium hydroxide, 1 part of water.

 Make a soft gel tincture by a method that includes the following steps:

(1) Extraction of Paeonia lactiflora: Take the medicinal materials of Paeonia lactiflora, add 7 times the amount of water to decoction and extract 4 times, each time for 1 hour, filter, combine the filtrates, and concentrate the filtrates to a relative density of about 1.16, Add 2 times the amount of 95% ethanol solution, leave it to stand for 18 hours, filter, recover the filtrate and concentrate it to a relative density of about 1.16, add an equal amount of 0.2mol / L NaHC0 ₃ solution, stir to dissolve, Add 4 times the amount of ethyl acetate and extract 3 times, combine the ethyl acetate extracts, recover the ethyl acetate to near dry, and then add 3 times the amount of 80 ° /. The ethanol solution was dissolved, filtered, and then the filtrate was recovered ethanol and concentrated to a relative density of about 1.16, and spray-dried to obtain a white tincture extract powder;

 (2) Preparation of the contents of soft gelatine: Take the soybean oil with the ratio, heat it to about 58 ° C, add the soybean phospholipid and beeswax in the ratio, and after dissolving and mixing, add the ratio Menthol oil, mix well, add the white peony extract powder obtained in step (1) while stirring, and continue stirring for 50 minutes after the addition is complete, and then mix evenly with colloid mill. Let stand for 1 0 Spare for more than an hour;

(3) Preparation of soft film: first prepare about 5% (g / g) sodium hydroxide solution for use; another appropriate amount of purified water is added, the acrylic resin II and acrylic resin III are added in the proportion, stirred for 50 minutes, and left to stand For 40 minutes, add the pre-prepared sodium hydroxide solution while stirring. After alkalizing for 50 minutes, transfer to a gelatinizer, heat to about 85 ° C and keep it for 1 hour under stirring. Then add the ratio Gelatin, glycerin, and ethyl paraben, continue to heat and stir to completely dissolve the gelatin, keep it at 85 ° C for 1 hour, and remove some water by vacuuming to keep the moisture in it at about 27%. After sieving, it is transferred to a stable plastic barrel, and it is kept at 55-60 ° C for more than 12 hours to obtain a glue solution. Then, the glue solution is made into a soft film with uniform thickness and a certain elasticity according to a conventional process for use;

 (4) Making soft gelatin capsules: The contents of the soft gelatin capsules and the soft gelatin capsules on the soft film are pressed into a soft gelatin capsule of 0.5 g / capsule.

Embodiment 12 This embodiment is an enteric soft gel liniment, where:

 The drug substance components of the contents of the soft gum tincture are: 1 part of peppermint oil, 180 parts of peony, 1.5 parts of soybean oil, 0.08 parts of soybean phospholipids, and 0.007 parts of beeswax.

 The soft film is composed of the following weight ratio components: 3 parts of gelatin, 1.2 parts of glycerin, 1 part of acrylic resin II, 0.2 parts of acrylic resin III, 0.012 parts of paraben ethyl ester, 0.18 parts Sodium hydroxide, 3 parts of water.

 The surface of the preparation is also coated with an enteric film coating.

 An enteric soft gel tincture is prepared by a method that includes the following steps:

(1) Extraction of Paeonia lactiflora: Take the medicinal materials of Paeonia lactiflora and add 8 times the amount of water to decoction and extract 3 times, 2.5 hours each time, filter, combine the filtrates, and concentrate the filtrates to a relative density of about 1. 14, add 3 times the amount of 90% ethanol solution, leave the precipitate for 20 hours, filter, recover the filtrate and concentrate the ethanol to a relative density of about 1.14, add an equal amount of 0.3 mol / L NaHC0 ₃ solution, stir to make Dissolve, add 3 times the amount of ethyl acetate and extract 4 times, combine the ethyl acetate extracts, recover the ethyl acetate to near dry, then add 4 times the amount of 75% ethanol solution to dissolve, filter, and then recover the filtrate to ethanol and concentrate to The relative density is about 1.14, and spray-dried to obtain white tincture extract powder;

 (2) Preparation of the contents of soft gelatine: take the soybean oil with the ratio, heat it to about 57 ° C, add the soybean phospholipid and beeswax in the ratio, and after dissolving and mixing, add the ratio Menthol oil, mix well, add the white peony extract powder obtained in step (1) while stirring, and continue to stir for 40 minutes until the addition is complete, and then mix evenly with colloid mill. Let stand for 12 hours Above spare

 (3) Preparation of soft film: first prepare an approximately 8% (g / g) sodium hydroxide solution for use; another appropriate amount of purified water is added, the acrylic resin II and acrylic resin III are added in the proportion, stirred for 40 minutes, and left to stand For 100 minutes, add the pre-prepared sodium hydroxide solution while stirring. After alkalizing for 80 minutes, transfer to a gelatinizer, heat to about 84 ° C and keep it for 40 minutes under stirring. Then add the ratio Gelatin, glycerin, and ethyl paraben, continue to heat and stir to completely dissolve the gelatin, keep it at 84 ° C for 40 minutes, and remove some water by vacuuming to control the water content to about 35%. After sieving, it is transferred to a stable plastic barrel, which is kept under the condition of 55-60 ° C for more than 12 hours to obtain a glue solution. Then, the glue solution is made into a thin film with a uniform thickness and a certain elasticity according to a conventional process for use;

 (4) Made of enteric soft gelatin: The soft gelatin content and the soft gelatin on a soft film are compressed into a soft gelatin gel by a press of 0.5 g / granule, and then coated on the surface according to a conventional coating process. An enteric film coating is sufficient.

 Example 13

 This embodiment is an enteric soft gel liniment, where:

The drug substance components of the contents of the soft capsule are: 1 part of peppermint oil, 80 parts of red pepper, 2.2 parts of peanut oil, 0. 05 parts of soybean phospholipid, Q. 05 parts of beeswax.

 The soft film is composed of the following weight ratio components: 3 parts of gelatin, 1.5 parts of glycerin, 0.8 parts of acrylic resin II, 0.4 parts of acrylic resin III, 0.01 parts of paraben ethyl ester, 0. 21 parts sodium hydroxide, 2.5 parts water.

 The surface of the preparation is also coated with an enteric film coating.

 An enteric soft gel tincture is prepared by a method that includes the following steps:

(1) Extracting red scallion: take the ratio of red scallion medicinal materials, add 9 times the amount of water to cook and extract twice, the first 2.5 hours, the second 1.5 hours, filter, combine the filtrates, and Lmol The filtrate was concentrated to a relative density of about 1.17, 4 times the amount of 80% ethanol solution was added, the precipitate was left for 32 hours, filtered, the filtrate was recovered ethanol and concentrated to a relative density of about 1.17, and an equal amount of 0.1 lmol was added. / L NaHC0 ₃ solution, stir to dissolve, add 5 times the amount of ethyl acetate and extract twice, combine the ethyl acetate extracts, recover the ethyl acetate to dryness, then add 2 times the 85% ethanol solution to dissolve, and filter Then, the filtrate was recovered to ethanol and concentrated to a relative density of about 1.17, and spray-dried to obtain red scallion extract powder;

 (2) Preparation of soft gelatine contents: Take the proportion of peanut oil, heat it to about 58 ° C, add the proportion of soybean phospholipid and beeswax, dissolve and mix, and add the proportion of mint Mix the vegetable oil, and then add the red chrysanthemum extract powder obtained in step (1) while stirring. Continue to stir for 30 minutes until the addition is complete, and then mix evenly with colloid mill. Let stand for more than 12 hours. Spare

 (3) Preparation of soft film: first prepare about 6.5% (g / g) sodium hydroxide solution for use; another appropriate amount of purified water is added, the acrylic resin II and acrylic resin III are added in the proportion, and stirred for 30 minutes, Allow to stand for 60 minutes, and then add the pre-prepared sodium hydroxide solution while stirring. After alkalizing for 60 minutes, transfer to a gelatinizer, heat to about 82 ° C and keep it for 45 minutes under stirring. Proportion of gelatin, glycerin, and ethyl paraben. Continue heating and stirring to completely dissolve the gelatin. Incubate at 82 ° C for 40 minutes. Vacuum to remove part of the water, and control the water content to about 30%. After 80 mesh sieve, it is transferred to a stable plastic barrel, and it is kept at 55-60 ° C for more than 12 hours to obtain a glue solution. Then, the glue solution is made into a soft film with a uniform thickness and a certain elasticity according to a conventional process. Spare

 (4) Made of enteric soft gelatin capsules: The contents of the soft gelatin capsules and the soft capsules on a soft capsule press are pressed into a soft gel capsule of 0.5g / granule, and then the surface is coated with a conventional coating process for one An enteric film coating is sufficient.

 Embodiment 14

 This embodiment is a soft gum tincture, wherein: the raw material medicine components of the soft gum tincture are: 1 part of peppermint oil, 100 parts of peony, 2.5 parts of soybean vegetable oil, 0.1 part of soybean phospholipid, 0.1 Portions of beeswax.

The soft film is composed of the following weight ratio components: 3 parts gelatin, 1.5 parts glycerin, 1 part water. Preparation: (1) Extract the Paeonia lactiflora according to the extraction method in step (1) of Example 8 to obtain Paeonia lactiflora extract powder;

(2) taking the ratio of soybean vegetable oil, heating it to about 55 ° C, adding the ratio of soybean phospholipid and beeswax, dissolving and mixing the mixture, adding the ratio of mint oil, and mixing, Add the Paeonia lactiflora powder obtained in step (1) while stirring, and continue to stir for about 30 minutes after the addition is complete, so that the mixture is homogeneous, and let stand for more than 12 hours for use;

 (3) Preparation of soft film: Take an appropriate amount of purified water, add the gelatin and glycerin in the proportions, heat and stir to completely dissolve the gelatin, and keep it at 85 ° C for 30 minutes after mixing the hooks, and remove some water by vacuum. Make the moisture content of 25%, and then transfer it to the glue stabilization barrel after passing through a 80 mesh sieve. Keep the glue at 55-60 ° C for more than 12 hours to obtain a glue solution. Then make this glue solution according to the conventional process. Prepare soft film with uniform thickness and elasticity;

 (4) Making soft gelatin capsules: The contents of the soft gelatin capsules and the soft gelatin capsule press on the soft film are pressed into a soft gelatin capsule of 0.5 g / grain, and then the process is completed.

 Example 15

 This embodiment is a soft gel tincture, where:

 The drug substance components of the contents of soft capsules are: 1 part of peppermint oil, 80 parts of peony, 2.0 parts of soybean vegetable oil, and 0.1 part of beeswax.

 The soft film is composed of the following weight ratio components: 3 parts gelatin, 1.6 parts glycerin, 0.9 parts water. Preparation:

 (1) Extract the Paeonia lactiflora according to the extraction method in step (1) of Example 8 to obtain Paeonia lactiflora extract powder;

(2) Take the proportion of soybean vegetable oil, heat it to about 55 ° C, add the proportion of beeswax, dissolve and mix, add the proportion of menthol oil, mix well, and stir while stirring Add the Paeonia lactiflora powder obtained in step (1), and continue to stir for about 30 minutes after the addition is complete, so that the mixture is homogeneous, and let stand for more than 12 hours for use;

 (3) Preparation of soft film: Take an appropriate amount of purified water, add the gelatin and glycerin in the proportions, heat and stir to completely dissolve the gelatin, and keep it at 85 ° C for 30 minutes after mixing the hooks, and remove some water by vacuum. Make the moisture content of 20%, and then transfer it to a glue stabilization barrel after passing through a 80 mesh sieve. Keep the glue at 55-60 ° C for more than 12 hours to obtain a glue solution. Then make this glue solution according to the conventional process. Prepare soft film with uniform thickness and elasticity;

 (4) Making soft gelatin capsules: The contents of the soft gelatin capsules and the soft gelatin capsule press on the soft film are pressed into a soft gelatin capsule of 0.5 g / grain, and then the process is completed.

 Embodiment 16

 This embodiment is a soft gel tincture, where:

The drug substance components of the contents of soft capsules are: 1 part of peppermint oil, 130 parts of red pepper, 3 parts of soybean plant Oil.

 The soft film consists of the following weight ratio components: 3 parts gelatin, 1.2 parts glycerin, 0.5 parts water. Preparation:

 (1) Extracting red peony according to the extraction method in step (1) of Example 8 to obtain red peony extract powder;

(2) Take the proportion of soybean vegetable oil, heat it to about 55 ° C, add the proportion of menthol oil, mix well, and then add the red scallion extract powder obtained in step (1) while stirring, Continue to stir for about 30 minutes after the addition is complete, make the mixture uniform, and let it stand for more than 12 hours;

 (3) Preparation of soft film: Take an appropriate amount of purified water, add the proportion of gelatin and glycerin, heat and stir to completely dissolve the gelatin, mix and keep at 85 ° C for 30 minutes, and remove some water by vacuum. Make the moisture content of 18%, and then transfer it to a stable plastic bucket after passing through a 80 mesh sieve. Keep the glue for more than 12 hours at 55-60 ° C to obtain a glue solution. Then make this glue solution according to the conventional process. Soft film with uniform and certain elasticity;

 (4) Making soft gelatin capsules: The contents of the soft gelatin capsules and the soft gelatin capsule press on the soft film are pressed into a soft gelatin capsule of 0.5 g / grain, and then the process is completed.

 Example 17

 This embodiment is a soft gel tincture, where:

 The drug substance components of the contents of soft capsules are: 1 part of peppermint oil, 160 parts of red pepper, 2.8 parts of soybean vegetable oil.

 The soft film is composed of the following weight ratio components: 3 parts of gelatin, 1.2 parts of glycerin, 0.5 parts of water, 0.01 parts of paraben ethyl ester.

 Preparation:

 (1) Extracting red peony according to the extraction method in step (1) of Example 8 to obtain red peony extract powder;

(2) taking the proportion of soybean vegetable oil, heating it to about 55 ° C, adding the proportion of menthol oil, mixing well, and then adding the red chrysanthemum extract powder obtained in step (1) while stirring, Continue to stir for about 30 minutes after the addition is complete, make the mixture uniform, and let it stand for more than 12 hours;

 (3) Preparation of soft film: Take an appropriate amount of purified water, add the gelatin and glycerin in the ratio, heat and stir to completely dissolve the gelatin, add the ratio of ethyl paraben, and mix at 85 °. Incubate for 30 minutes at C, remove some water by vacuuming, so that the moisture content is 33%. After passing through 80 mesh sieve, transfer it to a stable plastic barrel. Incubate at 55-60 ° C for more than 12 hours. Obtain a glue solution; then use this glue solution to make a soft film with a uniform thickness and a certain elasticity according to conventional processes;

 (4) Making soft gelatin capsules: press the soft gelatin capsules into the contents of the soft gelatin capsules and press the soft gelatin capsules into 0.1 soft gelatin capsules.

Embodiment 18 This embodiment is a soft gel tincture, where:

 The drug substance components of the contents of soft capsules are: 1 part of peppermint oil, 180 parts of red peony, and 2 parts of soybean vegetable oil.

 The soft film is composed of the following weight ratio components: 3 parts gelatin, 1.2 parts glycerin, 0.5 parts water, 0.02 parts sorbic acid.

 Preparation:

 (1) Extracting red peony according to the extraction method in step (1) of Example 8 to obtain red peony extract powder;

(2) taking the proportion of soybean vegetable oil, heating it to about 55 ° C, adding the proportion of menthol oil, mixing well, and then adding the red chrysanthemum extract powder obtained in step (1) while stirring, Continue to stir for about 30 minutes after the addition is complete, make the mixture uniform, and let it stand for more than 12 hours;

 (3) Preparation of soft film: Take an appropriate amount of purified water, add the gelatin and glycerin in the ratio, heat and stir to completely dissolve the gelatin, add the sorbic acid in the ratio, and mix at 85 ° C. After holding for 30 minutes, vacuum remove part of the water to make the moisture content suitable. After passing through a 80 mesh sieve, transfer it to a stable plastic bucket and keep it at 55-60 ° C for more than 12 hours to obtain a glue solution. This glue solution is made into a soft film with uniform thickness and elasticity according to the conventional process for future use;

 (4) Making soft gelatin capsules: press the soft gelatin capsules into the contents of the soft gelatin capsules and press the soft gelatin capsules into 0.1 soft gelatin capsules.

 Example 19

 This embodiment is a soft gel tincture, where:

 The drug substance components of the contents of soft capsules are: 1 part mint oil, 100 parts white peony, 80 parts red peony,

2 servings of soybean vegetable oil.

 The soft film is composed of the following weight ratio components: 3 parts of gelatin, 1.2 parts of glycerin, 0.4 parts of water, 0.01 parts of paraben.

 Preparation method of the above embodiments:

 (1) Extracting red peony according to the extraction method in step (1) of Example 8 to obtain red peony extract powder;

(2) Take the proportion of soybean vegetable oil, heat it to about 55 ° C, add the proportion of menthol oil, mix well, and then add the chitin extract powder obtained in step (1) while stirring, Continue to stir for about 30 minutes after the addition is complete, make the mixture uniform, and let it stand for more than 12 hours;

(3) Preparation of soft film: Take an appropriate amount of purified water, add the proportion of gelatin and glycerin, heat and stir to completely dissolve the gelatin, and then add the proportion of propyl paraben to the mixture. C was held for 30 minutes under the condition of C, and a portion of water was removed by vacuuming, so that the moisture content therein was 28 ° /. After passing through an 80-mesh sieve, it is transferred to a stable plastic barrel, and it is kept at 55-60 ° C for more than 12 hours to obtain a glue solution. Then, the glue solution is made into a uniform thickness with a certain elasticity according to conventional processes. Spare film (4) Making a soft gelatin capsule: the contents of the soft gelatin capsule and the soft gelatin tablet press on the soft gelatin capsule are pressed into a soft gelatin capsule of 0.5 g / granule.

 The pharmaceutical excipients used in the above examples were purchased from legal excipient manufacturers, among which: magnesium stearate is a product of Shanghai Yuanji Chemical Co., Ltd .; corn starch is a product of Zhenyu Huanyu Pharmaceutical Excipients Factory in Jiangsu; gelatin is Qinghai Products of Gelatin Co., Ltd .; glycerin is a product of Hangzhou Asia-Pacific Chemical Equipment Co., Ltd .; paraben, ethyl paraben and ethyl paraben are products of Xinke Chemical Co., Ltd. of Langxi County, Anhui; soybean oil and peanut oil are Products of Shenzhen Nanhai Oil Industry Co., Ltd .; tea oil is the product of Fangchenggang Xinhai Oil Industry Co., Ltd .; beeswax is the product of Dalian Sangdi Natural Products Co., Ltd .; soybean phospholipid is the product of Beijing Meiyas Phospholipid Technology Co., Ltd .; sodium hydroxide is the product of Lanxi Guanglong. Products of Chemical Materials Co., Ltd .; Acrylic Resin II and Acrylic Resin III are products of Huzhou Jiantianming Pharmaceutical Co., Ltd. The enteric film coating used in each of the above examples was an enteric film coating premix obtained from Chengdu Taishan Film Coating Factory.

Claims

Rights request

1. A traditional Chinese medicine for treating irritable bowel syndrome, which contains the following weight ratio of raw materials: 1 part of peppermint oil and 80-180 parts of white peony / red peony.

 2. The traditional Chinese medicine for treating irritable bowel syndrome according to claim 1, characterized in that it contains the following raw materials in weight ratio: 1 part of peppermint oil and 100-160 parts of white peony / red peony.

 3. The traditional Chinese medicine for treating irritable bowel syndrome according to claim 2, characterized in that: it contains the following raw materials in weight ratio: 1 part of peppermint oil and 130 parts of white peony / red peony.

 4. The traditional Chinese medicine according to claim 1, characterized in that the white peony / red peony is treated by a conventional extraction method, and the obtained extract is mixed with 1 part of peppermint oil.

 5. The traditional Chinese medicine according to claim 4, characterized in that: the extract obtained by treating white peony / red peony with a conventional method is an extract powder obtained by water extraction and purification.

 6. The traditional Chinese medicine according to claim 5, wherein the dosage form of the traditional Chinese medicine is a tablet, a hard gel liniment or a soft gel liniment.

 7. The traditional Chinese medicine according to claim 6, characterized in that: the dosage form of the traditional Chinese medicine is a soft capsule, which is composed of the contents of a soft capsule containing the above-mentioned pharmaceutical ingredients and a soft capsule shell covering the surface; and The capsule contents also contain any one or more medicinal excipients selected from vegetable oil, soybean phospholipids, beeswax, glycerin, polyethylene glycol, propylene glycol, and isopropanol; soft capsule shells contain gelatin, glycerin and water.

 8. The traditional Chinese medicine according to claim 7, characterized in that: the soft gum shell further contains sorbic acid, acrylic resin II, acrylic resin III, water, titanium dioxide, sodium hydroxide, sucrose, nipagin B Any one or more of esters, parabens and propyl parabens.

 9. The traditional Chinese medicine according to claim 8, characterized in that: the contents of the soft gum tincture further contain the following components by weight ratio: 1. 5-3 parts of soybean oil, 0.02-0.08 parts Soy phospholipids and 0.02 to 0. 08 parts of beeswax; the components of the soft gum shell are: 3 parts of gelatin, 1. 2-1. 8 parts of glycerin, 0.6-1.0 parts of acrylic resin II, 0. 2-0. 6 parts of acrylic resin III, 0. 008-0. 012 parts of paraben ethyl ester, 0. 18-0. 24 parts of sodium hydroxide, 2-3 parts of water.

 10. The traditional Chinese medicine according to claim 9, characterized in that: the content of the soft gum tincture contains the following components in a weight ratio of: 1 part of peppermint oil, 130 parts of extract of white tincture / red tincture Powder, 2.2 parts of soybean oil, 0.05 parts of soybean phospholipids, and 0.05 parts of beeswax; the components of the soft gelatin shell are: 3 parts of gelatin, 1.5 parts of glycerin, 0.8 parts of acrylic resin II, 0 4 parts of acrylic resin III, 0.01 part of paraben ethyl ester, 0.21 part of sodium hydroxide, 2.5 parts of water.

11. The traditional Chinese medicine according to any one of claims 6 to 10, wherein the surface of the tablet, hard gel tincture or soft gel tincture is further coated with an enteric film coating.

12. A method for preparing a traditional Chinese medicine according to claim 5, comprising the following steps:

(1) Extracting white scallion / red scallion: take the ratio of the white scallion or scallion medicinal materials, add 6-10 times the amount of water to cook and extract 2-4 times, each time 1-3 hours, filter, and combine The filtrate was concentrated to a relative density of 1.10-1.20, 2-4 times the amount of an 80-95% ethanol solution was added, and the precipitate was allowed to stand for 12-48 hours, filtered, and the filtrate was recovered to ethanol and concentrated to a relative density of 1. 10-1. 20, add equal amount of 0.1-0.3mol / L NaHC0 ₃ solution, stir to dissolve, add 3-5 times the amount of ethyl acetate to extract 2-4 times, and combine the ethyl acetate extracts Recover ethyl acetate to near dry, then add 2-5 times the amount of 75-85% ethanol solution to dissolve, filter, and then recover the filtrate to ethanol and concentrate to a relative density of 1. 10- 1. 20, spray-dried to obtain Paeonia lactiflora / red paeonia extract powder;

 (2) Preparation of preparations: Take the mentioned ratio of menthol oil and mix it with the white scallion / red scallion extract powder prepared in step (1) to prepare various preparations according to conventional techniques.

 13. A method according to claim 12, wherein the dosage form of step (2) is a soft gum tincture; and wherein the contents of the soft gum tincture are prepared according to the following procedure: take 1.5 to 3 parts soybean oil, After heating to 55-60 ° C, 0.02-0. 08 parts of soybean phospholipid and 0.02-0. 08 parts of beeswax are added, and after dissolving and mixing, add the proportion of peppermint oil and mix, Add the white scallion / red scallion extract powder prepared in step (1) while stirring, continue to stir for 20-60 minutes, make it fully mixed, and let it stand for more than 8 hours for use;

 0-1 acrylic acid, and the following steps were used to prepare a soft film: first use 0. 18-0. 24 parts of sodium hydroxide to prepare a 3- 10% sodium hydroxide solution for use; another appropriate amount of purified water was added, 0.6-1. 0 parts acrylic acid Resin II and 0.2-2. 6 parts of acrylic resin III, stirred for 20-60 minutes, left to stand for 40-120 minutes, and then added the pre-prepared sodium hydroxide solution while stirring. After alkalizing for 40-100 minutes, Under stirring conditions, heat to 80-85 ° C and keep for 30-60 minutes, then add 3 parts of gelatin, 1. 2-1. 8 parts of glycerin and 0.008-0. 012 parts of paraben ethyl ester, continue heating Stir the gelatin completely, keep it at 80-85 ° C for 30-60 minutes, and remove some of the water by vacuum to control the water content to 18-35 ° /. After passing through an 80-mesh sieve and holding at 55-60 ° C for more than 10 hours to stabilize the glue, the glue solution is prepared; then the glue solution is made into a soft film according to the conventional process for later use;

 In addition, the contents of the soft capsule and the soft film are made into a soft capsule.

 14. A method according to claim 12 or 13, further comprising the steps:

 (3) The preparation prepared in step (2) is coated with an enteric film coating.