Use of the preparation of Mailuoshutong in treatment of anal fistula

Abstract

The application belongs to the field of traditional Chinese medicines, and particularly relates to a new use of a Mailuoshutong preparation, namely, a use of the Mailuoshutong preparation in preparation of a medicine for treating anal fistula. The Mailuoshutong preparation is mainly prepared from Huangqi, Jinyinhua, Huangbai, Cangzhu, Yiyiren, Xuanshen, Danggui, Baishao, Gancao, Shuiji, Wugong and Quanxie. The clinical use result shows that the Mailuoshutong preparation (granules / pills) has a high effective rate in treating anal fistula, can obviously improve the clinical symptoms of the patients with anal fistula, and reduce the pain of the patients, thereby providing a new drug selection for the patients with anal fistula.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of traditional Chinese medicine, and relates to a new medical use of a malu Shutong preparation, in particular to an application of the malu Shutong preparation in the preparation of a medicine for treating anal fistula. BACKGROUND

[0002] Anal fistula is a granulomatous tunnel around the anal canal or rectum, which is composed of three parts: internal orifice, fistula, and external orifice. The internal orifice is usually located at the anal sinus above the dentate line, and is usually one. The external orifice is on the perianal skin, and can be one or more. Anal fistula is a common disease in clinical practice, and its main clinical symptom is anal induration, which can repeatedly break and flow pus, and patients can have different degrees of pus flow, pain and other symptoms.

[0003] China is the earliest country to recognize "fistula" disease. The "Cangwen Chuiwei, Shixia can be fistula" in Shanhaijing Zhongshanjing first explicitly proposed the disease name of "anal fistula". In traditional Chinese medicine, the causes of anal fistula are summarized as post-ulceration of anal abscess, chronic cough due to deficiency, external invasion of six evils, improper diet, internal injury due to seven emotions, chronic hemorrhoids, and insufficient blood circulation around the anus.

[0004] Traditional Chinese medicine has a long history of treating anal fistula, and has formed a relatively complete theoretical system and unique treatment technology. The external treatment of traditional Chinese medicine is divided into external drug treatment and surgical treatment. The external drug treatment mainly includes traditional Chinese medicine flushing method, traditional Chinese medicine dressing method, and traditional Chinese medicine fumigation method. The surgical treatment includes pipe removal method, thread hanging method and incision method.

[0005] Anal fistula is still mainly treated by surgical treatment in the current conventional treatment process, and the conservative treatment is supplemented by traditional Chinese medicine treatment. However, due to the large individual differences of patients, some patients cannot undergo conventional surgical treatment.

[0006] Chinese patent CN1201787C discloses a traditional Chinese medicine composition for treating thrombophlebitis, which comprises 12 kinds of medicinal materials of Huangqi, Jinyinhua, Huangbai, Cangzhu, Yiyiren, Xuanshen, Danggui, Baishao, Gancao, Shuizhi, Wugong and Quanxie. The traditional Chinese medicine composition has the functions of clearing heat and resolving toxins, removing blood stasis and dredging collaterals, and has a good effect on the clinical treatment of thrombophlebitis. It also has a certain preventive and therapeutic effect on thrombotic occlusive vasculitis. The product based on the patent has been marketed, and the product name is "Malu Shutong Granules / Pills". It is mainly used for treating thrombophlebitis caused by damp-heat and blood stasis in collaterals, and lower limb swelling, pain, dark red skin or accompanied by cord-like material caused by non-acute deep vein thrombosis. SUMMARY

[0007] The inventors would like to explain that the use of the maltaiehuotong preparation in the preparation of a drug for treating anal fistula is derived from the feedback of patients using the maltaiehuotong preparation (granules / pills) in clinical use. Some patients with thrombophlebitis of superficial veins who accidentally found that the clinical symptoms of anal fistula were also improved when they took maltaiehuotong granules / pills to treat thrombophlebitis of superficial veins fed back this discovery. Based on this use feedback, the inventors further researched and verified the effect of maltaiehuotong preparation on anal fistula, and found that maltaiehuotong preparation also has good therapeutic effect on anal fistula.

[0008] One of the purposes of the present application is to provide a new medical use of maltaiehuotong preparation, i.e. the use in the preparation of a drug for treating anal fistula.

[0009] Further, the anal fistula is low anal fistula or high anal fistula.

[0010] Preferably, the low anal fistula is low simple anal fistula or low complex anal fistula; the high anal fistula is high simple anal fistula or high complex anal fistula.

[0011] The anal fistula of the present application can be caused by perianal abscess, ulcerative colitis, Crohn's disease, malignant tumor and / or perianal trauma infection, etc.

[0012] The maltaiehuotong preparation of the present application includes but is not limited to maltaiehuotong granules and maltaiehuotong pills.

[0013] Further, the maltaiehuotong granules are mainly prepared from the following components:

[0014]

[0015] The maltaiehuotong pills are mainly prepared from the following components:

[0016]

[0017] The beneficial effects of the present application mainly include:

[0018] (1) Pharmacological experiments have confirmed that maltaiehuotong pills have good therapeutic effect on anal fistula model rabbits, and can significantly improve the perianal secretion of anal fistula rabbits and reduce the number of fistula.

[0019] (2) The maltaiehuotong preparation has good therapeutic effect on anal fistula patients in clinical application, can significantly improve the clinical symptoms such as perianal swelling and pain, pus discharge, and reduce the pain of patients, providing a new drug selection for anal fistula patients. DETAILED DESCRIPTION

[0020] Example 1 Commercially available maltaiehuotong granules (Guojiazhunzi Z19991025)

[0021] Ingredients:

[0022] Radix Astragali 500g, honeysuckle 500g, golden cypress 250g, atractylodes 250g, coix seed 500g, scrophularia 500g, angelica 250g, white peony root 250g, liquorice 83g, leech 250g, centipede 20g, scorpion 83g.

[0023] Example 2 commercially available Mailuoshutong pills (Guojiazhunzi Z20090636)

[0024] Ingredients:

[0025] Radix Astragali 833g, honeysuckle 833g, golden cypress 417g, atractylodes 417g, coix seed 833g, scrophularia 833g, angelica 417g, white peony root 417g, liquorice 138g, leech 417g, centipede 33g, scorpion 138g.

[0026] I. Therapeutic effect of Mailuoshutong preparation on anal fistula in rabbits

[0027] To verify the effect of Mailuoshutong preparation in the treatment of anal fistula, the inventors carried out related pharmacodynamic test research. It should be noted that the modeling method and detection index described in the following pharmacodynamic experiment are carried out according to the method described in the existing technology or literature.

[0028] The inventors would like to point out that the following experimental researches are carried out on the basis of the safety of acute toxicity test and long-term toxicity test, and the dosages in the experimental researches are within the safe dosage range.

[0029] 1 Material

[0030] 1.1 Animal:

[0031] Rabbits, 2-4 kg, rabbit age 8-12 months, experimental animal license number: SYXK(Lu)2018 0008, provided by Lunan Pharmaceutical Group Co., Ltd., and adaptively fed for one week before the experiment.

[0032] 1.2 Drug, reagent

[0033] 1.2.1 Drug

[0034] Mailuoshutong pills (Guojiazhunzi Z20090636, Lunan Hupu Pharmaceutical Co., Ltd.)

[0035] Levofloxacin tablets (Guojiazhunzi H20067723, 0.2g, calculated as levofloxacin)

[0036] 1.2.3 Dosage

[0037] Mai Luoshutong Pills: 3.36 g / kg (high dose), 1.68 g / kg (medium dose), 0.84 g / kg (low dose)

[0038] Levofloxacin Tablets: 0.014 g / kg

[0039] 2. Modeling, grouping and administration

[0040] 2.1 Modeling method

[0041] After the rabbits were fasted for 12 h and water deprived for 6 h, they were anesthetized, their limbs were fixed, and the excess perianal fur was cut off to expose the anus, which was then routinely disinfected. For the model rabbits, a rubber band was inserted from the inside of the anal sphincter above the dentate line to the outside, passing through the perianal region, and fixed to prevent slipping and causing anal congestion. The control rabbits were similarly treated, except that a small round needle was used instead of a rubber band.

[0042] Ten days after the operation, the morphology around the anal fistula tract was observed. If the fistula did not heal or a string-like object, hard knot, or mass could be felt during digital rectal examination, the modeling was considered successful.

[0043] 2.2 Grouping and administration

[0044] Forty model rabbits were randomly divided into a model group, three Mai Luoshutong Pill (high, medium, and low) dose groups, and a levofloxacin tablet group, with 8 rabbits in each group. Eight control rabbits were used as a sham operation group.

[0045] The rabbits in each administration group were given the corresponding drugs by gavage. The rabbits in the sham operation group and the model group were given an equal amount of distilled water by gavage. The administration was continued for 20 days.

[0046] 3 Observation indicators

[0047] 3.1 Perianal secretions

[0048] 0 points: clean and dry anus with no obvious secretions; 1 point: slightly moist anus with a small amount of secretions that can soak half a sterilized cotton swab; 2 points: moist anus with a moderate amount of secretions that can soak one sterilized cotton swab; 3 points: wet anus with a large amount of secretions that can soak 1.5 sterilized cotton swabs; 4 points: extremely wet anus with an excessive amount of secretions that can soak two or more sterilized cotton swabs.

[0049] 3.2 Histopathological examination

[0050] The perianal and anal fistula tissues of the rabbits were taken to prepare specimens, and the number of fistula tracts and inflammatory cells were observed.

[0051] 3.3 Statistical processing

[0052] The data were analyzed by SPSS 22.0 software. Measurement data were expressed as One-way ANOVA was used for multiple comparisons, and independent sample T test was used for two-group comparison. P<0.05 was considered statistically significant.

[0053] 4. Results and Conclusions

[0054] 4.1 Changes of perianal secretion

[0055] Before administration, only a few rabbits in the sham operation group had a small amount of perianal secretion, which was light in color and thin in texture. The rest of the rabbits in each group had a large amount of perianal secretion, which was thick in texture and yellow in color. On the 10th day of administration, the perianal secretion of the model group rabbits decreased, which was thick in texture and yellow in color. The perianal secretion of the rest of the rabbits in the administration group decreased significantly, which was light in color and white-yellow in color. There was a significant difference (P<0.01). On the 20th day of administration, the perianal secretion of the model group rabbits decreased compared to before, which was light in color and white-yellow in color, but the texture was thick. The perianal secretion of the rest of the rabbits in the administration group decreased significantly, which was light in color and thin in texture. There was a significant difference (P<0.01).

[0056] Among the administration groups, the high and medium dose groups of Mailuoshutong Pills changed the most, and the low dose group and the levofloxacin tablet group changed similarly.

[0057] Table 1 Comparison of perianal secretion of rabbits in each group

[0058]

[0059] Note: Compared with the sham operation group, *P<0.01;

[0060] Compared with the model group, # P<0.01.

[0061] 4.2 Histopathological changes

[0062] Before administration, only 2 rabbits in the sham operation group had 1 or 2 fistulas, and the rest of the rabbits in each group had about 10-13 fistulas, and a large number of inflammatory cells were visible in the perianal tissue. After 20 days of administration, the number of fistulas in the model group was about 8-10, and the number of fistulas in the rest of the administration group was 3-6, which decreased significantly, and the number of inflammatory cells in the perianal tissue decreased significantly.

[0063] II. Clinical application of Mailuoshutong preparations

[0064] Mailuoshutong Pills have been successfully used to treat 15 patients with anal fistula, with a treatment efficiency as high as 90.3%, and a low recurrence rate after treatment. A small number of cases are given below to illustrate.

[0065] Case 1: Qian, 36 years old, clinical diagnosis of low complex anal fistula, more than 3 months, treated with MaiLu Shu Tong pill, 3 days after taking the medicine, the perianal swelling and pain was relieved, 5 days after taking the medicine, the amount of perianal pus was significantly reduced, 9 days after taking the medicine, the perianal swelling and pain and pus disappeared.

[0066] Case 2: Sun, 53 years old, clinical diagnosis of high single anal fistula, more than 7 months, treated with MaiLu Shu Tong pill, 5 days after taking the medicine, the perianal swelling and pain was relieved, 8 days after taking the medicine, the amount of perianal pus was significantly reduced, 12 days after taking the medicine, the perianal swelling and pain and pus disappeared.

Claims

1. Use of Mailuoshutong granules or Mailuoshutong pills in the preparation of a drug for treating anal fistula, characterized in that, the Mailuoshutong granules are prepared from the following components in parts by weight: 500 parts by weight of Huangqi, 500 parts by weight of Jinyinhua, 250 parts by weight of Huangbai, 250 parts by weight of Cangzhu, 500 parts by weight of Yiyiren, 500 parts by weight of Xuanmai, 250 parts by weight of Danggui, 250 parts by weight of Baishao, 83 parts by weight of Gancao, 250 parts by weight of Shuizhi, 20 parts by weight of Wugong, and 83 parts by weight of Quanxie; the Mailuoshutong pills are prepared from the following components in parts by weight: 833 parts by weight of Huangqi, 833 parts by weight of Jinyinhua, 417 parts by weight of Huangbai, 417 parts by weight of Cangzhu, 833 parts by weight of Yiyiren, 833 parts by weight of Xuanmai, 417 parts by weight of Danggui, 417 parts by weight of Baishao, 138 parts by weight of Gancao, 417 parts by weight of Shuizhi, 33 parts by weight of Wugong, and 138 parts by weight of Quanxie.

2. Use according to claim 1, characterized in that, The anal fistula is low anal fistula or high anal fistula.

3. Use according to claim 2, characterized in that, The low anal fistula is low simple anal fistula or low complex anal fistula.

4. The use according to claim 2, characterized in that, The high anal fistula is high simple anal fistula or high complex anal fistula.

5. The use according to claim 1, characterized in that, The anal fistula is caused by perianal abscess, ulcerative colitis, Crohn's disease, malignant tumor and / or anal canal trauma infection.

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