AU2021106470A4

AU2021106470A4 - Yao-folk medicine compositions for treating gallstones, decoctions, capsules and applications thereof

Info

Publication number: AU2021106470A4
Application number: AU2021106470A
Authority: AU
Inventors: Jianye DAI; Yue Gao; Xiaowei He; Xin Huang; Qian QIN; Li Wu; Xing YIN; Man ZHANG; Qi Zhang
Original assignee: Guangxi University of Chinese Medicine; First Affiliated Hospital of Guangxi Medical University
Current assignee: Guangxi University of Chinese Medicine; First Affiliated Hospital of Guangxi Medical University
Priority date: 2021-08-23
Filing date: 2021-08-23
Publication date: 2021-11-04
Anticipated expiration: 2029-08-23

Abstract

OF THE DISCLOSURE The present disclosure belongs to the field of Yao-folk medicine composition, and in particularly relates to a Yao-folk medicine composition for treating gallstones, decoctions, capsules, and applications thereof. The Yao-folk medicine composition for treating gallstones, comprising the following components: Schizophragma integrifolium, slate fern, womh ziomx buerng, Herba Cladostachvdis, Lygodium flexuosum, Lysimachia christinae Hance, Gardenia jasminoides Ellis root, plantain herb, Mussaenda philippica, Pyrrosia lingua, and Fructus Aurantii. The Yao-folk medicine composition provided by the present disclosure is for the purpose of treating patients with vigorous hot, and the Yao-folk medicine composition mainly uses Schizophragma integrifolium, slate fern, and womh ziomx buemg as the main medicines, which have the effect of removing stones and dampness; Lysimachia christinae Hance, Lygodium flexuosum and Pyrrosia lingua play the role of removing stones and dissolving stones, and are used as the adjuvant medicines. Herba Cladostachvdis, Gardenia jasminoides Ellis root, plantain herb, Mussaenda philippica, and Fructus Aurantii have the functions of clearing heat, removing dampness, and treating stranguria, and are used as the messenger medicines. The composition is combined with functions of wind medicine and fighting medicine, and all components work together to play the role of dissolving stones, removing stones, clearing heat and treating stranguria. It can be seen from the examples that after the patient is treated with the Yao-folk medicine composition provided by the present disclosure, the effective rate of gallstone treatment is as high as 69.40 %, and the gallbladder condition and bile metabolism of the patients are effectively improved. ABSTRACT DRAWING - Fig 1 17994003_1 (GHMatters) P117086.AU 1/2 le007 2e ,007 I%r+0LJ' le007 Tie(ints 10~ 1333 1.6 720 23.3333 2.67 30 33.333.336.6 667 FIGi 14-0000 1e007 4e-0000 2e0000, Tm- ioC s 10 1333 16.666 2 0 23.3333 6.6667 30 33.33336.66 FIG2

Description

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Tie(ints 10~ 1333 1.6 720 23.3333 2.67 30 33.333.336.6 667

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FIG2

YAO-FOLK MEDICINE COMPOSITIONS FOR TREATING GALLSTONES, DECOCTIONS, CAPSULES AND APPLICATIONS THEREOF TECHNICAL FIELD

[01] The present disclosure belongs to the field of Yao-folk medicine composition, and in particularly relates to a Yao-folk medicine composition for treating gallstones, decoctions, capsules, and applications thereof.

BACKGROUNDART

[02] With the rapid development of China's economy in recent years, people's living standards have a qualitative leap, and the level of medical technology has also been greatly improved., and existing survey data show that the incidence of primary intrahepatic bile duct stones is showing a downward trend as a whole. However, the Guangxi Zhuang Autonomous Region is located in the southwest border. Due to the influence of multiple factors such as regional climate, diet and economic development, its incidence has not changed much compared with the past, especially in rural areas, therefore, exploring effective drugs for the treatment of gallstones is of great significance to Guangxi region.

[03] At present, the academic community has made considerable in-depth and systematic research on the pathogenesis of bile duct stones. However, in the treatment, the symptomatic intervention of surgical treatment is preferred, but the recurrence rate in the liver bile duct stones is still high. Especially young patients are more common, which brings heavy psychological pressure and economic burden to patients and their families, seriously affects the work and life of patients, and causes greater physical and mental pain. Therefore, exploring effective prevention and treatment measures and drugs is a difficult problem that needs to be solved in the medicalfield today.

[04] In Yao-folk medicine, gallstone is classified as "converting cellar to form balls", and the Yao-folk name is weih gaauv gitv mbaengx, which is equivalent to "stone strangury" and "urolithiasis" in traditional Chinese medicine diseases. Converting cellar to form balls is a common disease. After subjecting to the damp-heat and evil poison, the body's balance is broken, and the damp-heat and evil gas rise and invade the bladder to form cellar nodules. Or improper diet results in endogenous damp-heat to make the body full of dampness and evil gas, and then the dampness and evil gas are injected and accumulated in the bladder, which torment urine to form sand and stones. Or due to insufficient endowment or prolonged illness from strain, or after a long period of leaching, the qi deficiency of spleen and kidney affects the qi's universal function, which leads to unfavorable bladder gasification, abnormal urine production and excretion, and the disease will develop over time. Due to detrimental to gasification, stone obstruction is generated to cause pain; and heat injury can cause hematuria. The prior art lacks a medicine that can effectively prevent and treat gallstones and reduce the rate of residual stones after surgery.

SUMMARY

[05] In order to solve the above problems, the present disclosure provides a Yao-folk

1 17994003_1(GHMtters) P117086.AU medicine composition for treating gallstones, decoctions, capsules, and applications thereof. The Yao-folk medicine composition for treating gallstones provided by the present disclosure has the effects of dissolving stones and removing stones, clearing heat and treating stranguria, can effectively reduce the residual stone rate after surgery, can also prevent the recurrence of stones, and improve the life quality of patients.

[06] In order to achieve the above object, the present disclosure provides the following technical schemes:

[07] The present disclosure provides a Yao-folk medicine composition for treating gallstones, wherein comprising the following components in parts by mass: 1-3 parts of Schizophragma integrifolium, 1-3 parts of slate fern, 1-3 parts of womh ziomx buerng, 1-3 parts of Herba Cladostachvdis, 1-3 parts of Lygodium flexuosum, 1-3 parts of Lysimachia christinae Hance, 1-3 pats of Gardeniajasminoides Ellis root, 1-3 parts of plantain herb, 1-3 parts of Mussaendaphilippica, 1-3 parts of Pyrrosia lingua, and 1-3 parts of FructusAurantii.

[08] Preferably, the dosage form of the Yao-folk medicine composition comprises a decoction and a capsule.

[09] The present disclosure also provides a decoction of the Yao-folk medicine composition described in the above technical schemes, the decoction comprises the above Yao-folk medicine composition and water.

[10] The present disclosure also provides a capsule of the Yao-folk medicine composition described in the above technical schemes, the capsule comprises the above Yao-folk medicine composition and a capsule shell.

[11] Preferably, each capsule contains 0.45 g of Yao-folk medicine composition in the capsule.

[12] The present disclosure also provides an application of the above Yao-folk medicine composition or the above decoction of the Yao-folk medicine composition or the above capsule of the Yao-folk medicine composition in the preparation of a medicine for the treatment of gallstones.

[13] Preferably, when the medicine is a decoction, the taking method includes: the decoction is to be administered twice a day to patients at a dose of 150-165 mL/times.

[14] Preferably, when the medicine is a capsule, the taking method includes: the capsule is to be administered three times a day to patients at a dose of 6 capsules/times.

[15] The present disclosure provides a Yao-folk medicine composition for treating gallstones, comprising the following components: Schizophragma integrifolium, slate fern, womh ziomx buerng, Herba Cladostachvdis, Lygodium flexuosum, Lysimachia christinaeHance, Gardeniajasminoides Ellis root, plantain herb, Mussaendaphilippica, Pyrrosia lingua, and FructusAurantii. The Yao-folk medicine composition provided by the present disclosure is for the purpose of treating patients with vigorous hot, and the Yao-folk medicine composition mainly uses Schizophragma integrifolium, slate fern, and womh ziomx buerng as the main medicines, which have the effect of removing stones and dampness; Lysimachia christinae Hance, Lygodium flexuosum and Pyrrosia lingua play the role of removing stones and dissolving stones, and are used as the adjuvant medicines. Herba Cladostachvdis, Gardeniajasminoides Ellis root, plantain herb, Mussaenda philippica, and Fructus Aurantii have the functions of clearing heat,

2 17994003_1 (GHMatters) P117086.AU removing dampness, and treating stranguria, and are used as the messenger medicines. The composition is combined with functions of wind medicine and fighting medicine, and all components work together to play the role of dissolving stones, removing stones, clearing heat and treating stranguria. It can be seen from the examples that after the patient is treated with the Yao-folk medicine composition provided by the present disclosure, the effective rate of gallstone treatment is as high as 69.40 %, and the gallbladder condition and bile metabolism of the patients are effectively improved.

BRIEF DESCRIPTION OF THE DRAWINGS

[16] FIG.1 shows the GC-MS detection spectrum of bile in the treatment group before treatment;

[17] FIG. 2 shows the GC-MS detection spectrum of bile in the control group before treatment;

[18] FIG. 3 shows the GC-MS detection spectrum of internal standard;

[19] FIG. 4 shows the GC-MS detection spectrum of bile in the treatment group after treatment;

[20] FIG. 5 shows the GC-MS detection spectrum of bile in the control group after treatment;

[21] FIG. 6 is a schematic diagram of the main components of the GC-MS metabolite data of the bile of the patients in the two groups.

DETAILED DESCRIPTION OF THE EMBODIMENTS

[22] The present disclosure provides a Yao-folk medicine composition for treating gallstones, wherein comprising the following components in parts by mass: 1-3 parts of Schizophragma integrifolium, 1-3 parts of slate fern, 1-3 parts of womh ziomx buerng, 1-3 parts of Herba Cladostachvdis, 1-3 parts of Lygodium flexuosum, 1-3 parts of Lysimachia christinae Hance, 1-3 pats of Gardeniajasminoides Ellis root, 1-3 parts of plantain herb, 1-3 parts of Mussaendaphilippica, 1-3 parts of Pyrrosia lingua, and 1-3 parts of Fructus Aurantii; the dosage form of the Yao-folk medicine composition preferably comprises a decoction and a capsule.

[23] The Yao-folk medicine composition provided by the present disclosure has the effects of dissolving stones and removing stones, clearing heat and treating stranguria, which can effectively reduce the residual stone rate after surgery, can also prevent the recurrence of stones, and improve the life quality of patients. At the same time, it also has the advantages of low cost, good treatment effect, and no adverse reactions. The present disclosure prepares the Yao-folk medicine composition as a decoction or a capsule, which is beneficial for patients to take, and can effectively improve the acceptance of patients.

[24] The raw materials of the traditional Chinese medicine composition of the present disclosure include 1-3 parts of Schizophragma integrifolium, and more preferably 2 parts. In the present disclosure, the Yao-folk name of the Schizophragma integrifolium is nzunx deic buerng, which is a combination of wind medicine and fighting medicine. In the present disclosure, it has the effects of diuresis and stone removal, promoting blood circulation and removing blood stasis, reducing swelling and relieving pain.

3 17994003_1 (GHMatters) P117086.AU

[25] Based on the mass parts of Schizophragma integrifolium, the raw materials of the traditional Chinese medicine composition of the present disclosure include 1-3 parts of slate fern, more preferably 2 parts. In the present disclosure, the Yao-folk name of the slate fern is Wianghn qimv, which is a wind medicine, and comes from the "Yao Medicine Clinical Prescriptions Collection" published by Guangxi Science and Technology Press in 2018. In the present disclosure, it has the effect of diuresis, removing stones, cooling blood, hemostasis, clearing heat, detoxifying and relieving asthma.

[26] Based on the mass parts of Schizophragma integrifolium, the raw materials of the traditional Chinese medicine composition of the present disclosure include 1-3 parts of womh ziomx buerng, and more preferably 2 parts. In the present disclosure, the Yao-folk name of the womh ziomx buerng is uomh ziemx buerng, which belongs to fighting medicine. In the present disclosure, it has the effects of clearing heat and dampness, regulating lungs, resolving phlegm, reducing swelling and relieving pain.

[27] Based on the mass parts of Schizophragma integrifolium, the raw materials of the traditional Chinese medicine composition of the present disclosure include 1-3 parts of Herba Cladostachvdis, more preferably 2 parts. In the present disclosure, the Yao-folk name of Herba Cladostachvdis is Nduohnzanghbuerng, that is Suberect Spatholobus Stem, which has the effect of nourishing blood, invigorating blood, and dredging collaterals in the middle phase of the present disclosure.

[28] Based on the mass parts of Schizophragma integrifolium, the raw materials of the traditional Chinese medicine composition of the present disclosure include 1-3 parts of Lygodium flexuosum, more preferably 2 parts. In the present disclosure, the Yao-folk name of the Lygodiumflexuosum is Muh gux suix, which belongs to wind medicine. In the present disclosure, it has the effects of diuresis, treating stranguria, clearing lumps, detoxification, cooling blood, and hemostasis.

[29] Based on the mass parts of Schizophragma integrifolium, the raw materials of the traditional Chinese medicine composition of the present disclosure include 1-3 parts of Lysimachia christinae Hance, more preferably 2 parts. In the present disclosure, the functions of the Lysimachia christinae Hance in the Yao-folk medicine composition of the present disclosure are clearing heat, detoxification, treating stranguria, diuresis, and dissolving stones.

[30] Based on the mass parts of Schizophragma integrifolium, the raw materials of the traditional Chinese medicine composition of the present disclosure include 1-3 parts of Gardeniajasminoides Ellis root, more preferably 2 parts. In the present disclosure, the functions of Gardeniajasminoides Ellis root in the Yao-folk medicine composition of the present disclosure are clearing heat, removing dampness, cooling blood and hemostasis.

[31] Based on the mass parts of Schizophragma integrifolium, the raw materials of the traditional Chinese medicine composition of the present disclosure include 1-3 parts of plantain herb, more preferably 1 part. In the present disclosure, the functions of the plantain herb in the Yao-folk medicine composition of the present disclosure are clearing damp and promoting diuresis.

[32] Based on the mass parts of Schizophragma integrifolium, the raw materials of the

4 17994003_1 (GHMatters) P117086.AU traditional Chinese medicine composition of the present disclosure include 1-3 parts of Mussaendaphilippica, more preferably 1 part. In the present disclosure, the functions of the Mussaenda philippica in the Yao-folk medicine composition of the present disclosure are clearing heat, detoxifying, and relieving heat and dampness.

[33] Based on the mass parts of Schizophragma integrifolium, the raw materials of the traditional Chinese medicine composition of the present disclosure include 1-3 parts of Pyrrosia lingua, and more preferably 1 part. In the present disclosure, the function of Pyrrosia lingua in the Yao-folk medicine composition of the present disclosure is diuresis, treating stranguria, cooling blood, hemostasis, treatment of short urine and hematuria, pollakiuria and dysuria.

[34] Based on the mass parts of Schizophragma integrifolium, the raw materials of the traditional Chinese medicine composition of the present disclosure include 1-3 parts of Fructus Aurantii, more preferably 1 part. In the present disclosure, the functions of Fructus Aurantii in the Yao-folk medicine composition of the present disclosure are promoting qi movement, loosening the center, moving phlegm and dispersing glomus.

[35] The present disclosure does not specifically limit the source of the above raw materials, and conventional commercial products well-known to those skilled in the art can be used.

[36] The Yao-folk medicine composition mainly uses Schizophragma integrifolium, slate fern, and womh ziomx buemg as the main medicines, which have the effect of removing stones and dampness; Lysimachia christinae Hance, Lygodiumflexuosum and Pyrrosia lingua play the role of removing stones and dissolving stones, and are used as the adjuvant medicines. Herba Cladostachvdis, Gardenia jasminoides Ellis root, plantain herb, Mussaenda philippica, and Fructus Aurantii have the functions of clearing heat, removing dampness, and treating stranguria, and are used as the messenger medicines. The composition is combined with functions of wind medicine and fighting medicine, and all components work together to play the role of dissolving stones, removing stones, clearing heat and treating stranguria.

[37] The present disclosure also provides a decoction based on the above Yao-folk medicine composition, and the decoction comprises the above Yao-folk medicine composition and water. The preparation method of the decoction provided by the present disclosure is a conventional decoction boiling method well known to those skilled in the art. It is further preferred that: adding L of water to 1 kg of the raw material of the Yao-folk medicine composition for boiling, and each dose of Yao-folk medicine composition is preferably boiled to obtain 450-500 mL decoction. The decoction provided by the present disclosure can effectively improve the medicinal effect of the Yao-folk medicine composition.

[38] The present disclosure also provides a capsule based on the above Yao-folk medicine composition, and the capsule preferably includes the above Yao-folk medicine composition and a capsule shell. The preparation method of the capsule provided by the present disclosure is a conventional capsule preparation method well known to those skilled in the art. It is further preferred that mixing the raw materials of the Yao-folk medicine composition and crushing as an inner capsule and then filling the inner capsule into the capsule shell to obtain the capsule; each capsule preferably contains

5 17994003_1 (GHMatters) P117086.AU

0.45 g of the Yao-folk medicine composition. The capsule provided by the present disclosure is convenient for patients to take, and is beneficial to the control of drug intake dose.

[39] The present disclosure also provides an application of the above Yao-folk medicine composition or the above decoction of the Yao-folk medicine composition or the above capsule of the Yao-folk medicine composition in the preparation of a medicine for the treatment of gallstones; when the medicine is a decoction, the taking method includes: the decoction is to be administered twice a day to patients at a dose of 150-165 mL/times; when the medicine is a capsule, the taking method includes: the capsule is to be administered three times a day to patients at a dose of 6 capsules/times. The application of the capsule of the Yao-folk medicine composition provided by the present disclosure in the preparation of a medicine for treating gallstones is an effective and safe medicine for the treatment of gallstones.

[40] In order to further illustrate the disclosure, the following describes the Yao-folk medicine composition for treating gallstones, decoctions, capsules, and applications of the present disclosure will be described in detail with reference to the accompanying drawings and examples, but they cannot be understood as limiting the scope of protection of the present disclosure.

[41] Example 1

[42] The raw materials were prepared according to the following parts by mass: 2 parts of Schizophragma integrifolium, 2 parts of slate fern, 2 parts of womh ziomx buerng, 2 parts of Herba Cladostachvdis, 2 parts of Lygodium flexuosum, 2 parts of Lysimachia christinae Hance, 2 pats of Gardeniajasminoides Ellis root, 1 parts of plantain herb, 1 parts of Mussaenda philippica, 1 parts of Pyrrosia lingua, and 1 parts of Fructus Aurantii.

[43] 30 g of Schizophragma integrifolium, 30 g of slate fern, 30 g of womh ziomx buerng, 30 g of Herba Cladostachvdis, 30 g of Lygodiumfexuosum, 30 g of Lysimachia christinaeHance, 30 g of Gardeniajasminoides Ellis root, 15 g of plantain herb, 15 g of Mussaendaphilippica, 15 g of Pyrrosialingua, and 15 g of FructusAurantii were taken. The above raw materials were made into 600 capsules of the same amount according to the in-hospital preparation approved by the documents of Drug Administration of Guangxi Zhuang Autonomous Region (Gui Yao Jian Zhu [2003] No. 88), 3 times per day for patients, and 6 capsules each time.

[44] Example 2

[45] The raw materials were prepared according to the following parts by mass: 2 parts of Schizophragma integrifolium, 2 parts of slate fern, 2 parts of womh ziomx buemg, 2 parts of Herba Cladostachvdis, 2 parts of Lygodium flexuosum, 2 parts of Lysimachia christinae Hance, 2 pats of Gardeniajasminoides Ellis root, 1 parts of plantain herb, 1 parts of Mussaenda philippica, 1 parts of Pyrrosia lingua, and 1 parts of Fructus Aurantii.

[46] 111 g of Schizophragma integrifolium, 111 g of slate fern, 111 g of womh ziomx buerng, 111 g of Herba Cladostachvdis, 111 g of Lygodium flexuosum, 111 g of Lysimachia christinaeHance, 111 g of Gardeniajasminoides Ellis root, 56 g of plantain herb, 56 g of Mussaenda philippica, 56 g of Pyrrosia lingua, and 55 g of Fructus

6 17994003_1 (GHMatters) P117086.AU

Aurantii were taken. The above raw materials were added to IL of water and then decocted to obtain 450-500 mL of decoction, 2 times per day for patients, and 150-165 mL each time.

[47] Comparative Example

[48] Commercially available Xiaoyan Lidan tablets (manufacturer: Guangzhou Baiyunshan Pharmaceutical Factory; batch number: National Medicine Standard Z44022243), 3 times per day, and 6 tablets each time.

[49] Application Example 1

[50] 1. Case selection

[51] From January 2017 to October 2018, 151 patients with secondary common bile duct stones who were hospitalized in the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine were selected. This study was approved by the ethics committee of our hospital, and an informed consent form was signed with the research objects when they were conscious. The inclusion and exclusion criteria are as follows:

[52] Inclusion criteria: 1) Age: 18-70 years old; 2) Diagnostic criteria for chronic calculous cholecystitis with secondary common bile duct stones were drawn up with reference to the "Guiding Principles for Clinical Research of New Chinese Medicines (Trial)" published by Ministry of Health; 3) Color Doppler ultrasound or CT shows silt-like stones in the gallbladder and common bile duct stones, and the diameter of common bile duct stones is less than 2 cm; 4) The patient's cognitive function is normal, and he/she is informed of this study.

[53] Exclusion criteria: 1) Patients with gallstones more than 2 cm in diameter; or combined with calculus of intrahepatic duct; 2) Patients with malignant tumors; 3) Patients with severe cardiovascular and cerebrovascular diseases, acute lung infectious diseases, acute abdomen, acute cholecystitis, or severe liver and kidney functional impairment; 4) Patients during pregnancy or lactation; 5) Allergic to traditional Chinese medicine and/or western medicine used in this study; 6) Receiving other treatment within 1 week before inclusion; 7) Those who cannot cooperate with treatment due to mental disorders or psychological reasons, or have contraindications to ERCP treatment.

[54] 2. Case grouping

[55] The above 151 observed patients were all consistent with secondary common bile duct stones. According to the principle of randomized control in clinical prospective studies, the patients were numbered according to the time sequence when the patients were included as treatment objects. The random number of patients in each group will no longer be changed or adjusted throughout the study process.

[56] All the study objects were randomly divided into 2 groups. Among them, the treatment group was treated with the Yao-folk composition provided in the example for 77 cases, and the control group was treated with the Xiaoyan Lidan tablets provided by the Comparative Example for 74 cases. During the study, 9 cases were excluded because the patients were lost to follow-up and withdrew halfway through the study, including 5 cases in the treatment group and 4 cases in the control group, so 142 cases were actually included (treatment group, n = 72, control group, n = 70).

[57] 3. Therapeutic schemes

7 17994003_1 (GHMatters) P117086.AU

[58] (1) Scheme of the control group

[59] The Xiaoyan Lidan tablets described in the Comparative Example were provided to this group of patients continuously for 3 months.

[60] (2) Scheme of the treatment group

[61] The Yao-folk medicine composition described in the embodiment was provided to this group of patients continuously for 3 months.

[62] Both groups of patients were re-examined and evaluated after 3 months of continuous treatment.

[63] 4. Evaluation criteria for efficacy

[64] According to the "Guiding Principles for Clinical Research of New Chinese Medicines" by the Ministry of Health, the efficacy criteria were drawn up. According to the patient's symptoms and signs, the reduction of syndrome scores, and the results of color Doppler ultrasound examinations, the efficacies were divided into cured, markedly effective, effective, and ineffective, and then the effective rate was calculated.

[65] 5. Statistical methods

[66] The data was represented by( x ±S), SPSS 23.0 statistical software was used for analysis, and student's t test and x 2 test were used independently to calculate the differences between the groups. P < 0.05 was considered as significant difference. PCA statistics of endogenous metabolites of bile were conducted by using SIMCA software to import relative peak area data of metabolites, and the distribution of samples in the PCA model after normalization was observed.

[67] 6. Observation indicators and results

[68] (1) General item

[69] Before the start of the clinical trial study, statistics on the general information of all the research objects were carried out, mainly including basic information such as name, gender, ethnicity, weight, age, occupation, height; and treatment conditions such as family history, past history, allergy history, and medication history, etc. General information of the two groups of patients were compared at admission.

[70] Table 1 Comparison of general information of the two groups of patients at the time of admission( x ±S)

[711 treatment group control group t value P value (n= 72) (n= 70)

age (years old) 48.15 8.25 48.15 8.25 0.99 0.32

gender (man/ 27(37.5%)/ 24(34.3%)/ woman) 45(62.5%) 46(65.7 %)

body mass 24.0 0.89 23.7 0.88 0.75 0.46 index (kg/m2 )

course of 17.39 4.52 16.87 4.13 0.72 0.48 disease (month) syndrome 13.35 3.38 12.97 3.24 0.68 0.50

8 17994003_1 (GHMatters) P117086.AU scores (score)

[72] It can be seen from Table 1 that there is no significant difference in the scores of gender, age, body mass index, course of disease, and SLEFI between the two groups before treatment (P = 0.32, P = 0.73, P = 0.46, P = 0.48, P = 0.50). The two groups of patients are comparable.

[73] (2) Before and after treatment, the syndrome scores were used to score all the study objects to observe the improvement of syndromes.

[74] 1) Comparison of the effective rate of the two groups of patients

[75] The statistical results of the comparison of the effective rate of the two groups of patients are shown in Table 2

[76] Table 2 Comparison of treatment effects between two groups of patients

[771 cured markedly ineffect case effective effective 2 group (case effective ive r2 p No.(cs)rt(% ) (case) (case) treatmen 72 4 28 18 22 69.40° t group 4.82 0.0 control 4 70 2 24 10 34 51.40 group

[78] Note: Compared with the control group, the difference is statistically significant, *P < 0.05.

[79] It can be seen from Table 2 that the effective rate of the treatment group is 69.40 %; the effective rate of the control group is 51.40 %. The increase in the treatment group is significant, and the difference is statistically significant (P=0.04).

[80] 2) Comparison of syndrome scores before and after treatment between the two groups

[81] Table 3 Comparison of syndrome scores before and after treatment between the two groups( x ±S)

[82]

case group before treatment after treatment t P No.

treatment 72 13.35 3.38 5.45 1.74**** 16.67 < 0.001 group

control 70 12.97 3.24 8.44 3.07°° 8.98 < 0.001 group

t 0.68 -7.10

P 0.50 <0.001

9 17994003_1(GHMtters) P117086.AU

[83] Note: the difference is statistical significant compared to the data before treatment, °°P <0.001; the difference is statistical significant compared to the control group, **P <0.001.

[84] It can be seen from Table 3 that after comparison between groups: before treatment, the difference between the two groups of patients' syndrome scores is not statistically significant (P = 0.50); After treatment, compared with the control group, the syndrome score of the treatment group decreases significantly, and the difference is statistically significant (P < 0.001); intra-group comparison: compared with the data before treatment, the syndrome scores of the two groups of patients are significantly reduced after treatment, and the differences are statistically significant (P < 0.001), indicating that the Yao-folk medicine composition provided by the present disclosure can effectively achieve the therapeutic effect.

[85] (3) Before and after treatment, the research objects were admitted to the ultrasound department to perform color Doppler upper abdomen examination to observe the changes of the wall of gallbladder and gallstones. The comparison of color Doppler ultrasound changes in the upper abdomen of the two groups of patients before and after treatment is as follows.

[86] 1) The comparison of B ultrasound results of gallbladder between the two groups is shown in Table 4.

[87] Table 4 Comparison of the effective rate of gallbladder B ultrasound after treatment in the two groups

[88] poorsound transmission of wall roughness wall thickness cas effecti effect bile effecti grou e ve ive before after before after ve rate before after p No rate rate treatm treatm treatm treatm (%) treatme treatme (0%) (0%) ent ent ent ent nt nt (case) (case) (case) (case) (case) (case) treat ment 72 47 20 57.4* 64 33 48.4* 56 29 48.2 grou p contr ol 70 45 29 35.6 67 47 29.9 51 33 35.3 grou p X 4.43 4.76 1.83 P 0.04 0.03 0.24

[89] Note: The difference is statistical significant compared to the control group, *P < 10 17994003_1 (GHMatters) P117086.AU

0.05.

[90] It can be seen from Table 4 that before treatment, there is no statistically significant difference in the proportions of poor sound transmission, wall roughness, and wall thickness between the two groups (P > 0.05). After treatment, compared with the control group, the effective rate difference of the treatment group in the improvement of poor sound transmission difference and wall roughness is statistically significant (x2 = 4.43, P = 0.04; x2 = 4.76, P = 0.03); There is no significant difference in the treatment of gallbladder wall thickening (x2 = 1.83, P = 0.24).

[91] 2) The comparison results of the improvement of gallstone between the two groups of patients are shown in Table 5.

[92] Table 5 Improvement of gallstone in the two groups

[93]

case disappe decrease no change effective group X2 p No. ar (case) (case) (case) rate(%)

treatme 72 6 36 30 58.30* nt group 4.77 0.03 control 70 3 25 42 40.00 group

[94] Note: Compared with the control group, the difference is statistically significant, *P < 0.05.

[95] Note: Compared with the data before treatment, **P < 0.001; compared with the control group, AP < 0.001.

[96] It can be seen from Table 5 that the effective rate of patients in the treatment group is 58.30 %; the effective rate in the control group is 40.00 %. Comparing the effective rate between the two groups, the effective rate of the treatment group is significantly higher, and the difference is statistically significant (P = 0.03).

[97] (4) Before and after treatment, the patients were subjected to endoscopic retrograde cholangiopancreatography (ERCP) examination and bile was collected during stone removal, and sent to the laboratory for gas chromatography-mass spectrometry (GC-MS) detection, specifically: strictly standardized disinfection and sterilization of duodenoscope and other accessories were carried out before ERCP operation. 5 ml and 3-5 ml of bile were taken using two 5ml sterile syringes respectively, and stored at -80°C for examination to observe the changes of metabolomics characteristics of patients before and after treatment. The statistics and processing of data were carried out using the Chroma TOF4.3X software of LECO and LECO-Fiehn Rtx5 database.

[98] 1) The bile metabolomics characteristics of the two groups of patients were detected. The bile GC-MS detection spectra of the two groups of patients before and after treatment are shown in FIG. 1 to FIG. 5. FIG. 1 is the GC-MS detection spectrum of bile in the treatment group before treatment; FIG. 2 is the GC-MS detection spectrum of bile in the control group before treatment; FIG. 3is the GC-MS detection spectrum of 11 17994003_1(GHMtters) P117086.AU internal standard; FIG. 4 is the GC-MS detection spectrum of bile in the treatment group after treatment; FIG. 5 is the GC-MS detection spectrum of bile in the control group after treatment.

[99] It can be seen from FIG. 1 to FIG. 5 that the condition of the patients in the experimental group is effectively improved after treatment.

[100] 2) According to step (4), the PCA statistics of endogenous metabolite data of bile are obtained, and the statistical results are shown in FIG. 6.

[101] It can be seen from FIG. 6 that the main component distribution is concentrated in the 95% CI of the ellipse, before treatment, it is mainly distributed on the right side, and after treatment, it is mainly distributed on the left side. At the same time, it can be seen that the metabolites in the treatment group are mainly distributed in the upper left quadrant after treatment, and the control group is distributed in the lower left quadrant. It can be seen that there are significant differences in bile metabolite spectra between the two groups after drug treatment. It shows that the Yao-folk medicine composition provided by the present disclosure has the technical effect of influencing the condition of patients with gallstones.

[102] 3) According to step (4), the concentration statistics of endogenous metabolites are obtained. The statistical results are shown in Table 6-9.

[103] Table 6 Concentrations of bile metabolites in patients with different treatment schemes (relative peak area) ( x S)

[104] alanine citric acid lactic acid glutamic acid gro case before after before after before after before after up No. treatme treatme treatme treatme treatme treatme treatme treatme nt nt nt nt nt nt nt nt trea tme 0.39 0.87 1.08 0.52 0.19 4.26 3.97 0.57 nt 72 0.14A 0.26** 0.31** 0 . 1 3 AA 0.02** 0.77A 1.73** 0.20A groA up con trol 0.81 0.09 0.14 0.63 0.21 4.51 4.12 0.57 70 gro 0.22** 0.03 0.31** 0.12 0.03** 0.80 1.13** 0.19 up

[105] Table 7 Concentrations of bile metabolites in patients (relative peak area)( x +S)

[1061 ca glycine phenylalanine tyrosine glutamine gro se before after before after before after before after up N treatmen treatmen treatmen treatme treatme treatme treatme treatme 0. t t t nt nt nt nt nt

12 17994003_1 (GHMatters) P117086.AU trea tmue 0.29 1.01 4.59 0.74 8.22 0.94 0.025± 0.082 nt 72 0.16** 0 . 4 0 AA 1.63** 0.26A 2.72** 0.35A 0.015** 0.020A gro up con trol 0.28 0.63 4.49 0.79 8.41 1.03 0.03 0.09 70 gro 0.13** 0.33 1.43** 0.28 3.18** 0.37 0.017** 0.052 up

[107] Table 8 Concentrations of bile metabolites in patients (relative peak area) ( x S)

[108] ca cholesterol LDL glycerin malic acid gro se after before after before after before after before up N treatme treatmen treatme treatme treatme treatme treatme treatment 0. nt t nt nt nt nt nt trea tine 4.67 0.49 5.67 5.45 6.40 0.45 9.78 2.44 nt 72 1.00** 0 .1 7 AA 1.02' 1.16A 1.26** 0 10 AA 1.97** 0.35° gro up con trol 4.95 1.02 5.32 4.90 6.05 0.98 10.00+ 2.12 70 gro 1.30** 0.32 1.12° 1.08 1.33** 0.26 2.12** 0.57 up

[109] Table 9 Concentrations of bile metabolites in patients (relative peak area) ( x S)

[110] choline taurine case group before after No. before treatment after treatment treatment treatment treatment 72 0.21 0.035** 0.80 0. 1 5AA 0.17 0.03** 0.16 0.04** group control group 70 0.22 0.04** 0.46 0.12 3.85 0. 8 3 A A 1.04 0.14

[111]Note: Compared with the data after treatment, **P < 0.001; compared with the

data after treatment, *P>0.05; compared with the data in control group, AAP < 0.01; compared with the data in control group, AP>0.05; compared with the data in control group, P < 0.05.

[112] It can be seen from Table 6 to Table 9 that:

[113] Comparison between groups: After treatment, compared with the control group,

13 17994003_1 (GHMatters) P117086.AU the concentration of alanine, citric acid, glycine, cholesterol, glycerin, malic acid, choline, and taurine between the treatment group and the control group has a statistically significant difference (t = -7.404, P < 0.001; t = -2.93, P = 0.005; t = 3.41, P = 0.001; t = -6.72, P < 0.001; t = -8.813, P < 0.001; t = 2.163, P = 0.04; t =8.36, P < 0.001; t = 15.95, P < 0.001);

[114] Intra-group comparison: The metabolites of alanine, citric acid, lactic acid, glutamic acid, glycine, phenylalanine, tyrosine, glutamine, cholesterol, glycerin, malic acid, choline, and taurine of the two groups of patients before and after treatment have a statistically significant difference (t = 14.95, P < 0.001; t = 7.33, P < 0.001; t = -25.32, P < 0.001; t = 9.29, P < 0.001; t = -8.00, P < 0.001; t = 10.29, P < 0.001; t = 12.43, P < 0.001; t = -12.30, P < 0.001; t = 20.59, P < 0.001; t = 22.65, P < 0.001; t = 18.55, P < 0.001; t = -19.99, P < 0.001; t = -21.20, P < 0.001) and (t = 15.16, P < 0.001; t = 6.29, P < 0.001; t= -24.95, P < 0.001; t = 13.82, P < 0.001; t = -3.88, P = 0.001; t = 11.56, P <0.001; t= 10.32, P < 0.001; t = -4.88, P < 0.001; t = 12.55, P < 0.001; t = 15.96, P < 0.001; t = 15.99, P < 0.001; t = -9.87, P < 0.001; t = -27.30, P < 0.001), indicating that the Yao-folk composition provided by the present disclosure is effective in treating gallstones, dissolving stones and removing stones.

[115] In summary, Yao-folk medicine and Xiaoyan Lidan tablets have improved B-ultrasound and bile metabolomics characteristics of patients, but Yao-folk medicine has a stronger effect on dissolving and removing stones.

[116] Although the present disclosure has been disclosed in a preferred embodiment, it is not intended to limit the present disclosure, any person familiar with this technique, can do various modifications and modifications without departing from the spirit and scope of the present disclosure, so the scope of protection of the present disclosure should be defined by the claims.

[117] It is to be understood that, if any prior art publication is referred to herein, such reference does not constitute an admission that the publication forms a part of the common general knowledge in the art, in Australia or any other country.

[118] In the claims which follow and in the preceding description of the invention, except where the context requires otherwise due to express language or necessary implication, the word "comprise" or variations such as "comprises" or "comprising" is used in an inclusive sense, i.e. to specify the presence of the stated features but not to preclude the presence or addition of further features in various embodiments of the invention.

14 17994003_1 (GHMatters) P117086.AU

Claims

WHAT IS CLAIMED IS:

1. A Yao-folk medicine composition for treating gallstones, wherein comprising the following components in parts by mass: 1-3 parts of Schizophragma integrifolium, 1-3 parts of slate fern, 1-3 parts of womh ziomx buemg, 1-3 parts of Herba Cladostachvdis, 1-3 parts of Lygodiumflexuosum, 1-3 parts of Lysimachia christinaeHance, 1-3 pats of Gardeniajasminoides Ellis root, 1-3 parts of plantain herb, 1-3 parts of Mussaenda philippica, 1-3 parts of Pyrrosialingua, and 1-3 parts of FructusAurantii.

2. The Yao-folk medicine composition according to claim 1, wherein the dosage form of the Yao-folk medicine composition comprises a decoction and a capsule.

3. A decoction of the Yao-folk medicine composition according to claim 1 or 2, wherein comprising the Yao-folk medicine composition of claim 1 and water.

4. A capsule of the Yao-folk medicine composition according to claim 1 or 2, wherein comprising the Yao-folk medicine composition of claim 1 and a capsule shell.

5. The capsule according to claim 4, wherein each capsule contains 0.45 g of Yao-folk medicine composition in the capsule.

15 17994003_1 (GHMatters) P117086.AU