Application of honeysuckle arthralgia clearing preparation in preparation of medicine for preventing or treating functional dyspepsia

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to application of a honeysuckle arthralgia clearing preparation in preparation of a medicine for preventing or treating functional dyspepsia. The honeysuckle arthralgia clearing preparation is prepared from 11 raw medicinal materials including honeysuckle, caulis sinomenii, oldenlandia diffusa, radix scrophulariae, radix paeoniae alba, radix rehmanniae recen, pseudobulbus cremastrae seu pleiones, herba pyrolae, angelica sinensis, liquorice and centipede. Pharmacodynamic experiments prove that the honeysuckle arthralgia clearing granules have the effects of remarkably improving the gastric emptying function and the small intestine propelling function of rats, regulating and controlling the oxidative stress level, improving the serum MTL and GAS levels and reducing the serum VIP content, can be used for preventing or treating functional dyspepsia, and can be used for preventing or treating chronic pharyngitis. Especially, the traditional Chinese medicine composition has a remarkable effect on functional dyspepsia caused by stomach cold, spleen deficiency or liver depression. Meanwhile, the honeysuckle arthralgia clearing preparation is high in safety and small in toxic and side effects, and the clinical medication selection of patients is enriched.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and specifically relates to a new use of a Jinteng Qingbi preparation, in particular to an application of the Jinteng Qingbi preparation in preparing a drug for preventing or treating functional dyspepsia. Background Art

[0002] Functional dyspepsia (FD) is a highly prevalent functional gastrointestinal disorder characterized by early satiety, postprandial fullness, with or without abdominal pain or burning, and the absence of organic changes. Multicenter clinical trials have shown that 43% of dyspepsia patients are diagnosed with FD after gastroscopy. The accelerated pace of life and increased work intensity have led to increased mental stress and the development of unhealthy eating habits and lifestyle habits, which is a major factor in the increasing incidence of FD.

[0003] The pathogenesis of functional dyspepsia remains unclear, but most researchers believe that gastrointestinal motility disorders are one of its most fundamental pathological mechanisms. While not an organic disease, functional dyspepsia often triggers varying degrees of psychological distress, such as anxiety and depression, in patients. Patients are more prone to anxiety and depression than the general population, which not only impacts quality of life but also increases the risk of developing other medical conditions.

[0004] Functional dyspepsia is often treated with Western medicine using proton pump inhibitors and prokinetic drugs. While these medications are effective in the short term, their long-term efficacy is limited and recurrence is common. Traditional Chinese medicine offers significant advantages over Western medicine. Therefore, seeking treatment for functional dyspepsia with Traditional Chinese Medicine is crucial.

[0005] Traditional Chinese Medicine (TCM) has its own unique understanding of functional dyspepsia, considering it to fall under the categories of "fullness" and "epigastric pain." The description of "epigastric pain" is similar to the symptoms of abdominal pain syndrome, while the discussion of "fullness" is more consistent with the understanding of postprandial discomfort syndrome. Ancient physicians believed that this condition is often associated with external pathogenic factors, excessive fatigue, emotional imbalance, dietary irregularities, and congenital deficiencies. The disease is located in the stomach and is closely related to the liver and spleen. The pathological factors are often a combination of underlying deficiency and superficial excess, with spleen deficiency as the underlying cause and qi stagnation, blood stasis, food accumulation, phlegm-dampness, and other pathogenic factors as the superficial manifestations. The basic pathogenesis is spleen deficiency and qi stagnation, resulting in a disorganized and descending stomach.

[0006] Traditional Chinese Medicine (TCM) has accumulated extensive experience in treating functional dyspepsia. As one of the primary modalities for TCM treatment of functional dyspepsia, Chinese patent medicines (TCMs) are an integral part of TCM's therapeutic potential. Many guidelines and consensus recommendations mention TCMs in their recommended treatments. Because TCMs offer multiple components, multiple targets, multiple pathways of action, and minimal toxicity and side effects, exploring TCM treatments for functional dyspepsia is of paramount importance. Summary of the Invention

[0007] In order to enrich the drug selection for clinical treatment of functional dyspepsia, the purpose of the present invention is to provide a new use of Jinteng Qingbi preparation as a drug for treating functional dyspepsia.

[0008] Application of Jinteng Qingbi preparation in preparing medicine for preventing or treating functional dyspepsia.

[0009] Preferably, the functional dyspepsia is stomach cold type, spleen deficiency type, or liver depression type dyspepsia.

[0010] Preferably, the functional dyspepsia is of spleen deficiency and stomach cold type or liver depression and spleen deficiency type.

[0011] The Jinteng Qingbi preparation of the present invention is prepared from 11 raw medicinal materials: honeysuckle, Sinomenium sinomenium, Hedyotis diffusa, Scrophularia ningpoensis, White Peony Root, Rehmannia glutinosa, Trillium gracile, Herba Lycopodii, Chinese Angelica sinensis, Licorice and Scolopendra subspinipes.

[0012] The Jinteng Qingbi preparation is made from the following Chinese medicinal ingredients:

[0013]

[0014] The Jinteng Qingbi preparation is Jinteng Qingbi granules.

[0015] Jinteng Qingbi Granules is a marketed product of Lunan Houpu Pharmaceutical Co., Ltd., with the approval number of National Medicine Standard Z20123065 and the trade name of It has the effects of clearing away heat and detoxifying, promoting blood circulation and reducing swelling, relieving numbness and relieving pain.

[0016] Modern medicine shows that Jinteng Qingbi granules can increase the serum SOD content and reduce the MDA content in rats with functional dyspepsia models, indicating that Jinteng Qingbi preparations can improve the antioxidant capacity of model rats, regulate the level of oxidative stress, and thus protect gastric tissue from oxidative stress damage.

[0017] Jinteng Qingbi Granules can improve the gastric emptying function and small intestinal propulsion function of functional dyspepsia model rats, and have the effects of increasing serum MTL and GAS levels and reducing serum VIP content.

[0018] The Jinteng Qingbi Granules of the present invention adhere to traditional Chinese medicine theory and combine it with modern medical research theory. They provide a new option for the clinical treatment of functional dyspepsia and have broad application prospects in the preparation of drugs for the treatment of functional dyspepsia. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 The effect of Jinteng Qingbi granules on gastric emptying and small intestinal propulsion in functional dyspepsia model rats;

[0020] Figure 2 The effect of Jinteng Qingbi granules on the SOD content in the serum of functional dyspepsia model rats;

[0021] Figure 3 The effect of Jinteng Qingbi granules on the MDA content in the serum of functional dyspepsia model rats;

[0022] Figure 4 The effect of Jinteng Qingbi granules on the serum GAS content in functional dyspepsia model rats;

[0023] Figure 5 The effect of Jinteng Qingbi granules on the serum MTL content in functional dyspepsia model rats;

[0024] Figure 6 The effect of Jinteng Qingbi granules on the VIP content in serum of functional dyspepsia model rats. DETAILED DESCRIPTION

[0025] Based on the above contents of the present invention, according to common technical knowledge and customary means in this field, without departing from the above basic technical ideas of the present invention, other various forms of modifications, replacements or changes can be made.

[0026] The following further describes the above content of the present invention in detail through specific embodiments in the form of examples. However, this should not be construed as limiting the scope of the above subject matter of the present invention to the following examples. All technologies implemented based on the above content of the present invention fall within the scope of the present invention.

[0027] Experimental Example 1 Study on the Effect of Jinteng Qingbi Granules on Functional Dyspepsia Model Rats

[0028] 1 Materials and Methods

[0029] 1.1 Experimental animals and husbandry

[0030] Sixty healthy male SPF Sprague-Dawley rats, 6-8 weeks old, weighing 200 ± 20 g, were provided by Lunan Pharmaceutical Group Co., Ltd., Laboratory Animal License No. SYXK(Lu)2018-0008. The rats were housed at room temperature of 22-24°C, relative humidity of 40%-60%, and a 12-hour light / 12-hour dark cycle. The animals were allowed to move freely in their cages, eat, and drink. Experiments began after one week of acclimatization to the laboratory.

[0031] 1.2 Reagents and Instruments

[0032] AG285 electronic analytical balance (Mettler-Toledo, Switzerland), low-temperature high-speed centrifuge (Eppendorf, Germany), superoxide dismutase (SOD) test kit and malondialdehyde (MDA) test kit (Nanjing Jiancheng Bioengineering Institute), rat motilin (GAS) ELISA kit, rat gastrin (MTL) ELISA kit and rat vasoactive intestinal peptide (VIP) ELISA kit (Wuhan Boster Bioengineering Co., Ltd.), positive drug mosapride citrate tablets (Lunan Beite Pharmaceutical Co., Ltd., national medicine standard H19990317), and the test drug was Jinteng Qingbi granules (Lunan Houpu Pharmaceutical Co., Ltd., national medicine standard Z20123065).

[0033] 1.3 Animal grouping and model preparation

[0034] Using a random number table, 60 male SD rats were divided into 6 groups, namely, normal control group, model control group, positive control group, Jinteng Qingbi granule low-dose group (referred to as "experimental low-dose group"), Jinteng Qingbi granule medium-dose group (referred to as "experimental medium-dose group"), and Jinteng Qingbi granule high-dose group (referred to as "experimental high-dose group"), with 10 SD rats in each group.

[0035] Except for the blank control group, the rats in the other groups were fed with "tail clamping stimulation combined with irregular diet" to establish the FD model. The specific modeling method: the rats were fed with free water, food on odd days, and fasted on even days. During the feeding period, tail clamping stimulation was performed, that is, the distal 1 / 3 of the rat's tail was clamped with long forceps (the force was moderate, so as not to break the skin of the rat's tail), and the rat was provoked to fight with the rats in the same cage. The stimulation was performed 3 times a day, 30 minutes each time, for 7 consecutive days. If the rat's tail was broken or a wound appeared during the fight with the rats in the same cage, 0.15% iodine tincture could be applied to prevent infection of the damaged skin of the rat from interfering with the experimental data. The model was successful when the rat showed tension and anxiety reactions such as agitation and a significantly reduced food intake. After confirming the success of the model, drug treatment was given on the second day.

[0036] 1.4 Administration

[0037] After successful modeling, rats in each group were fed with conventional feed, and the dose was converted according to the clinical dosage of Jinteng Qingbi Granules. The low-dose, medium-dose and high-dose groups were orally administered with 1.35 g / kg / d, 2.7 g / kg / d and 5.4 g / kg / d of Jinteng Qingbi Granules, respectively. The positive control group was orally administered with 1.35 mg / kg / d of Mosapride Citrate Tablets. The normal control group and the model control group were orally administered with an equal volume of normal saline. All the drugs were administered once a day for 4 consecutive weeks.

[0038] 2. Detection indicators and methods

[0039] 2.1 General status observation

[0040] Observe and record the general behavioral changes of the rats, including mental state, free movement, auricle color, hair condition, stool morphology, etc. before and after modeling and during treatment.

[0041] 2.2 Body weight and food intake of rats

[0042] In the last week of treatment, a certain amount of food was weighed daily using an electronic balance to calculate the average daily food intake; after 4 weeks of administration, the body weight of rats in each group was measured using an electronic balance.

[0043] 2.3 Gastric emptying rate and small intestinal propulsion rate

[0044] After the last oral administration, the rats in each group were fasted but not water-deprived. 24 hours later, the rats in each group were gavaged with 2 mL of semi-solid nutrient paste at room temperature. 30 minutes later, the rats were anesthetized with 10% chloral hydrate and killed. The rat stomach was separated, wiped dry with clean filter paper, and weighed. The stomach was cut open along the greater curvature of the stomach. The residual nutrient paste in the stomach was thoroughly washed away. The clean filter paper was used to wipe dry and weighed again. The difference between the two weighings was the weight of the residual gastric content, and the residual gastric rate was calculated. The rat small intestine was separated, and the total length of the small intestine and the propulsion length of the small intestine (the migration distance of the black nutrient paste) were measured to calculate the propulsion rate of the small intestine.

[0045] Gastric residue rate = gastric residue weight / gavage nutrient paste weight × 100%

[0046] Small intestinal propulsion rate = small intestinal propulsion length / total small intestinal length × 100%

[0047] 2.4 Determination of serum superoxide dismutase (SOD) and malondialdehyde (MDA) levels

[0048] SOD content was determined using the hydroxylamine method according to the kit instructions. Samples were added and mixed thoroughly, and the cells were incubated at 37°C for 40 minutes. The absorbance of each well at 550 nm was compared using a microplate reader in the presence of a colorimetric reagent, and activity was calculated. MDA was determined using the thiobarbituric acid method according to the kit instructions. Samples were added and mixed thoroughly, and the cells were incubated at 95°C for 40 minutes. The supernatant was collected and the absorbance of each well at 532 nm was compared using a microplate reader, and the content was calculated.

[0049] 2.5 Serum motilin (GAS), gastrin (MTL), and vasoactive intestinal peptide (VIP) levels

[0050] After the final dose, rats in each group were fasted for 24 hours. Blood was collected from the abdominal aorta of each rat, placed in a heparinized centrifuge tube, and centrifuged. The supernatant was collected as the test serum. The ELISA kit instructions were strictly followed. The OD value of each well was recorded on a microplate reader at a wavelength of 450 nm. The absorbance OD value was plotted on the ordinate, and the concentration of the standard substance to be tested was plotted on the abscissa. A corresponding curve was generated, and the corresponding concentration level was calculated from the standard curve based on the OD value. Serum levels of GAS, MTL, and VIP were measured.

[0051] 2.6 Statistical analysis: SPSS 22.0 software was used for statistical analysis, and the experimental data were expressed as “mean ± standard deviation”. The data were expressed in the form of . One-way analysis of variance was used for comparison among multiple groups, and P < 0.05 was considered statistically significant.

[0052] 3 Experimental results

[0053] 3.1 Effect of Jinteng Qingbi Granules on the General Condition of Functional Dyspepsia Model Rats

[0054] After modeling, rats in each modeling group showed a gradual decrease in food intake and sleep compared to the normal control group. They also showed signs of restlessness, increased agitation, irritability, slowed reactions, laziness, and dull fur. No significant differences were observed in the modeling group. After drug administration, the condition of rats in each drug-treated group gradually improved, with various indicators showing varying degrees of improvement. Food intake essentially returned to normal, fur regained its luster, and autonomous activity increased.

[0055] 3.2 Effects of Jinteng Qingbi Granules on Body Weight and Food Intake in Functional Dyspepsia Model Rats

[0056] Among the various indicators reflecting the rats' physical function, body weight is the most intuitive. Compared with the normal control group, the model control group showed a significant decrease in body weight and food intake, with statistically significant differences (P < 0.001), further indicating the successful establishment of the animal model. Compared with the model control group, the positive control group and the high-dose experimental group showed a significant increase in body weight (P < 0.01). Food intake was also significantly increased in the positive control group and the low-, medium-, and high-dose experimental groups (P < 0.01, P < 0.001, respectively). The results are shown in Table 1.

[0057] Table 1 Effects of Jinteng Qingbi Granules on body weight and food intake of model rats

[0058]

[0059] Note: Compared with the normal control group, P<0.001 is marked with “ *** " Compared with the model control group, P < 0.01 is indicated by " ## ”, P<0.001 is indicated by “ ### "express.

[0060] 3.3 Effects of Jinteng Qingbi Granules on Gastric Emptying and Small Intestinal Propulsion Function in Functional Dyspepsia Model Rats

[0061] Compared with the normal control group, the gastric emptying rate and small intestinal propulsion rate of the rats in the model control group were significantly reduced (P < 0.001). In this experimental study, after the administration of Jinteng Qingbi Granules, the gastric emptying rate and small intestinal propulsion rate of the rats in the positive control group and the experimental medium and high dose groups were significantly increased compared with the model control group (P < 0.01, P < 0.001). See Table 2 and Figure 1 .

[0062] Table 2 Effects of Jinteng Qingbi Granules on gastric emptying rate and small intestinal propulsion rate in model rats

[0063]

[0064] Note: Compared with the normal control group, P<0.001 is marked with “ *** " Compared with the model control group, P < 0.01 is indicated by " ## ”, P<0.001 is indicated by “ ### "express.

[0065] 3.4 Effect of Jinteng Qingbi Granules on the Contents of SOD and MDA in Serum of Rats with Functional Dyspepsia

[0066] Compared with the normal control group, the SOD content in the serum of the rats in the model control group was significantly reduced (P < 0.001). In this experimental study, after the administration of Jinteng Qingbi Granules, the SOD content in the serum of the rats in the positive control group and the experimental medium and high dose groups was significantly increased compared with the model control group (P < 0.05, P < 0.001). See Table 3 and Figure 2 .

[0067] Compared with the normal control group, the serum MDA content of the rats in the model control group was significantly increased (P < 0.001). In this experimental study, after the administration of Jinteng Qingbi Granules, the serum MDA content of the rats in the positive control group and the experimental medium and high dose groups was significantly reduced compared with the model control group (P < 0.05, P < 0.01). See Table 3 and Figure 3 .

[0068] Table 3 Effects of Jinteng Qingbi Preparation on the Contents of SOD and MDA in Serum of Model Rats

[0069]

[0070] Note: Compared with the normal control group, P<0.001 is marked with “ *** " Compared with the model control group, P < 0.05 is indicated by " # ”, P<0.01 is indicated by “ ## ”, P<0.001 is indicated by “ ### "express.

[0071] 3.5 Effect of Jinteng Qingbi Granules on Serum MTL, GAS, and VIP Levels in Rats with Functional Dyspepsia

[0072] Compared with the normal control group, the MTL content in the serum of the rats in the model control group was significantly reduced (P < 0.001). In this experimental study, after the administration of Jinteng Qingbi Granules, the MTL content in the serum of the rats in the positive control group and the experimental medium and high dose groups was significantly increased compared with the model control group (P < 0.05, P < 0.001). See Table 4 and Figure 4 .

[0073] Compared with the normal control group, the serum GAS content of the rats in the model control group was significantly reduced (P < 0.01). In this experimental study, after the administration of Jinteng Qingbi Granules, the serum GAS content of the rats in the positive control group and the experimental high-dose group was significantly increased compared with the model control group (P < 0.05). See Table 4 and Figure 5 .

[0074] Compared with the blank control group, the VIP level in the model control group was significantly increased, and the difference was statistically significant (P < 0.001). In this experimental study, after the administration of Jinteng Qingbi preparation, the VIP content in the serum of rats in the positive control group and the experimental medium and high dose groups was significantly reduced compared with the model control group (P < 0.05, P < 0.01, P < 0.001). See Table 4 and Figure 6 .

[0075] Table 4 Effects of Jinteng Qingbi Preparation on GAS, MTL and VIP levels in serum of model rats

[0076]

[0077] Note: Compared with the normal control group, P<0.001 is marked with “ *** " Compared with the model control group, P < 0.05 is indicated by " # ”, P<0.01 is indicated by “ ## ”, P<0.001 is indicated by “ ### "express.

[0078] The Jinteng Qingbi Granules of the present invention adhere to traditional Chinese medicine theory and, in combination with modern medical research, have been shown to improve gastric emptying and small intestinal propulsion in rats with functional dyspepsia; increase serum SOD levels, decrease MDA levels, increase serum MTL and GAS levels, and decrease serum VIP levels. This indicates that the Jinteng Qingbi preparation can enhance the antioxidant capacity of model rats, regulate oxidative stress levels, and thus protect gastric tissue from oxidative stress damage, potentially preventing or treating functional dyspepsia.

Claims

1. Application of Jinteng Qingbi preparation in the preparation of drugs for preventing or treating functional dyspepsia.

2. The use according to claim 1, characterized in that The functional dyspepsia is stomach cold type, spleen deficiency type or liver depression type dyspepsia.

3. The use according to claim 1, characterized in that The functional dyspepsia is of spleen deficiency and stomach cold type or liver depression and spleen deficiency type.

4. The use according to claim 1, characterized in that The Jinteng Qingbi preparation is prepared from raw medicinal materials including honeysuckle, cyperus rotundus, hedyotis diffusa, Scrophularia ningpoensis, white peony root, raw rehmannia root, trillium, herba scutellariae, angelica, liquorice and centipede.

5. The use according to claim 4, characterized in that The Jinteng Qingbi preparation is made from the following components: 495 parts by weight of honeysuckle, 495 parts by weight of Sinomenium sinomenium, 330 parts by weight of Hedyotis diffusa 247.5 parts by weight of Scrophularia ningpoensis, 495 parts by weight of White Peony Root, 495 parts by weight of Rehmannia glutinosa 165 parts by weight of Psoralea corylifolia, 330 parts by weight of Herba Lycopodii, 247.5 parts by weight of Radix Angelicae Sinensis 165 parts by weight of liquorice and 33 parts by weight of centipede.

6. The use according to claim 5, characterized in that The Jinteng Qingbi preparation is Jinteng Qingbi granules.

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