Use of Danbai granules in preparing medicine for treating appendicitis and its complications

Abstract

The present invention belongs to the field of medical technology and specifically relates to a novel medical use of Danbai Granules, particularly the use of Danbai Granules in the preparation of a medicament for treating appendicitis and its complications. The Danbai Granules described herein can significantly inhibit the inflammatory response in rats with HCl-induced appendicitis models and significantly alleviate various symptoms in rabbits with acute appendicitis models. Furthermore, Danbai Granules are a pure traditional Chinese medicine preparation with no toxic side effects, providing a non-invasive treatment that can effectively alleviate patient suffering. They are effective in treating post-operative appendectomy infection, post-operative intestinal adhesions, and chronic appendicitis, opening up a new treatment approach for patients who are intolerant or fearful of surgery, and possessing significant social and economic benefits.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and specifically relates to a new use of Danbai granules, and in particular to the use of Danbai granules in preparing medicines for treating appendicitis and / or complications. Background Art

[0002] Appendicitis is an inflammatory condition caused by blockage or cessation of blood flow to the appendix, leading to appendicitis necrosis and subsequent bacterial infection. Common types include acute and chronic appendicitis. Acute appendicitis presents with acute abdominal pain, characterized by rapid onset, rapid progression, multiple changes, and severe symptoms. It is a common and critical clinical emergency. Acute appendicitis accounts for 10% to 15% of surgical abdominal pain admissions. It affects people of all ages, but is more common in young adults and in men than in women. Chronic appendicitis refers to the chronic inflammatory lesions of the appendix that remain after the symptoms of acute appendicitis subside. These lesions can include proliferation of fibrous connective tissue in the appendix wall, stenosis or occlusion of the appendix lumen, tortuosity of the appendix, and adhesions to surrounding tissues. Chronic appendicitis is characterized by an insidious onset, making it difficult to detect, a gradual onset of symptoms, and a prolonged course, ranging from several months to several years. There is no history of acute attacks at the beginning of the disease, and the disease does not recur during its course.

[0003] Regarding the pathogenesis of appendicitis, some scholars believe it is due to obstruction of the appendix lumen or bacterial infection, but for acute appendicitis, most believe it is due to obstruction of the appendix lumen. The appendix lumen is narrow and elongated, with a closed distal end. Under normal circumstances, peristalsis of the appendix wall can empty the lumen. However, hyperplasia of lymphoid follicles, obstruction by fecal stones and food debris, and torsion of the appendix can hinder the normal emptying of the appendix, leading to the accumulation of large amounts of mucus in the lumen, a gradual increase in intraluminal pressure, necrosis and ulceration, and creating conditions for bacterial infiltration.

[0004] Currently, Western medicine treatments for acute appendicitis primarily rely on surgery, but adverse surgical reactions such as tissue damage, postoperative infection, and abdominal adhesions are unavoidable. Traditional Chinese medicine classifies appendicitis as a "carbuncle in the intestine," a finding first mentioned in Suwen (Suwen, Jue Lun). Zhang Zhongjing of the Eastern Han Dynasty described the condition in his Golden Chamber as "a disease characterized by a skin-like appearance, a tight abdominal skin, and a tender, swollen appearance when pressed." These symptoms closely resemble those of a periappendiceal abscess. Carbuncle refers to a blockage of the body's qi and blood caused by toxic pathogens, resulting in a stagnant and blocked flow. Intestinal carbuncle, a type of internal carbuncle, occurs in the intestines. Traditional Chinese medicine attributes intestinal carbuncle etiology to four main factors: dietary indiscriminateness, emotional distress, overwork, and invasion by external pathogens. Overeating, excessive consumption of raw, cold and greasy food in daily life may damage the spleen and stomach qi and cause intestinal dysfunction, which may lead to stagnation of waste and internal generation of damp heat, which may accumulate in the intestines and form intestinal abscesses; excessive exertion, rapid running and falls may cause damage to the intestinal network, which may lead to intestinal abscesses; imbalance of cold and heat and unsuitable climate may lead to insufficient defense function and invasion of external pathogens, which may lead to intestinal abscesses; excessive joy and anger, worry and fear may lead to abnormal gastrointestinal metabolism, which may lead to qi stagnation and blood stasis, which may turn into heat over time and cause intestinal abscesses.

[0005] Traditional Chinese Medicine (TCM), leveraging its holistic approach to syndrome differentiation and treatment through personalized prescriptions, plays a significant role in alleviating clinical symptoms of appendicitis and reducing adverse reactions and recurrence rates after Western medical treatment. TCM believes that appendicitis originates in the intestines. Caused by dietary restrictions, excessive consumption of greasy, raw, and cold foods, a mismatch between cold and heat, and emotional imbalances, these conditions can lead to dysfunctional digestion, qi blockage, blood stasis, internal dampness and heat, and the decay of flesh and blood, resulting in intestinal abscesses. Consequently, toxic heat intensifies, invading the bloodstream, and the syndrome evolves into stasis, heat accumulation, toxic heat, and abscesses. The main therapeutic principles for appendicitis are clearing heat and detoxifying, promoting internal bowel movements, and promoting qi and blood circulation. TCM treatment of appendicitis fully embodies the traditional Chinese medical principle of addressing both the symptoms and the root cause, and treating both internal and external factors. It offers minimal invasiveness, low cost, rapid recovery, and reduces the complications and drug resistance associated with Western medication. Summary of the Invention

[0006] The purpose of the present invention is to provide a new medical use of Danbai granules, specifically to provide an application of Danbai granules in the preparation of a medicine for treating appendicitis.

[0007] Danbai Granules (approval number: National Medicine Standard Z20090651) is a protected Chinese medicine produced by Shandong New Era Pharmaceutical Co., Ltd. Danbai Granules are made from Paeonia suffruticosa, Sargentodon grandiflora, Viola yedoensis, Trillium, Curcuma zedoaria, Patrinia patriniae, Chuanxiong, White Peony Root, Smilax glabra, Bletilla striata, Hedyotis diffusa, Rhizoma Cibotii, Toona sinensis, and Chinese Angelica sinensis. They clear heat, resolve blood stasis, dispel dampness, and relieve pain. They are used for chronic pelvic inflammatory disease and for patients diagnosed with stasis-heat and dampness accumulation according to Traditional Chinese Medicine (TCM). Symptoms include lower abdominal pain, yellowish or odorous vaginal discharge, lumbar and sacral distension and pain, menstrual abdominal pain, low-grade fever, and a bitter taste in the mouth and dry throat.

[0008] The technical solutions of the present invention are as follows:

[0009] Use of Danbai granules in preparing medicine for treating appendicitis and / or complications after appendicitis surgery.

[0010] Danbai granules are used as the sole medicine in the preparation of medicines for treating appendicitis and / or complications after appendicitis surgery.

[0011] Use of Danbai granules combined with antibiotics in the preparation of a medicine for treating appendicitis and / or postoperative complications of appendicitis.

[0012] Preferably, the appendicitis is acute appendicitis or chronic appendicitis.

[0013] Further preferably, the acute appendicitis is simple appendicitis, suppurative appendicitis, gangrenous appendicitis or periappendiceal abscess.

[0014] The postoperative complications of appendicitis are one or more of incision infection, adhesive intestinal obstruction, postoperative bleeding, appendicitis or intestinal fistula.

[0015] The antibiotics are drugs that are effective against Gram-negative bacteria and / or anaerobic bacteria.

[0016] The antibiotic drugs are penicillins, cephalosporins, nitroimidazoles, quinolone antibiotics, aminoglycosides or lincomycins.

[0017] The antibiotics include but are not limited to penicillin sodium, cefuroxime, cefmetazole, cefazolin, cefoperazone sulbactam sodium, ceftazidime, ceftriaxone sodium, metronidazole, ornidazole, clindamycin, levofloxacin, gentamicin, etc.

[0018] The human dosage of the Danbai granules of the present invention is 0.2-1.0 g / kg / d.

[0019] Preferably, the human dose is 0.4-0.5 g / kg / d.

[0020] Compared with the prior art, the advantages of the present invention are:

[0021] 1. The Danbai granules of the present invention can significantly inhibit the inflammatory response of rats with acute appendicitis model and can significantly alleviate various symptoms of rabbits with acute appendicitis model.

[0022] 2. Danbai Granules are a pure traditional Chinese medicine preparation with no toxic side effects. It provides a non-invasive treatment that effectively alleviates patient suffering. It is effective for treating post-appendectomy infection, post-operative intestinal adhesions, and chronic appendicitis, addressing both the symptoms and the root cause. This opens up a new treatment avenue for patients who are intolerant or fearful of surgery. DETAILED DESCRIPTION

[0023] In order to enable those skilled in the art to fully understand the present invention, the present invention is further described below through specific examples. However, those skilled in the art should be aware that the examples of the present invention do not limit the present invention in any way.

[0024] Example 1 Study on the Effect of Danbai Granules on Acute Appendicitis Model Rats

[0025] 1 Experimental Materials

[0026] 1.1 Experimental Animals

[0027] Fifty healthy male Wistar rats (200 ± 20 g, clean-grade, provided by the Pharmacology Center of Lunan Pharmaceutical Group, license number SYXK(Lu)20180008) were used. They were housed for one week prior to the experiment and had free access to food and water, maintaining a 12-h circadian rhythm.

[0028] 1.2 Experimental instruments and reagents

[0029] BX53 biological microscope, Olympus, Japan.

[0030] Ampicillin sodium, national medicine standard number H13021628, produced by Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd. Danbai granules, national medicine standard number Z20090651, produced by Shandong Xinshidai Pharmaceutical Co., Ltd.

[0031] 2 Experimental methods

[0032] 2.1 Animal grouping

[0033] The experimental animals were randomly divided into 5 groups, namely model control group, positive control group, low-dose, medium-dose and high-dose experimental groups; each group had 10 animals.

[0034] 2.2 Modeling method

[0035] All rats in each group were fasted for 12 hours before modeling. The model was established as follows: 1.5 ml / kg of 3% sodium pentobarbital was injected intramuscularly. After anesthesia, a sterile laparotomy was performed, and 0.15 ml of 0.06N hydrochloric acid was injected into each of the four small veins of the appendix (two anterior and two posterior). After the injection, the injection site was compressed with sterile cotton balls to stop bleeding, and the abdominal cavity was then closed layer by layer.

[0036] 2.3 Administration

[0037] Drug administration began 24 hours after modeling. The positive control group received an injection of ampicillin sodium at 9 mg / kg every 6 hours. The low-, medium-, and high-dose groups were gavaged with Danbai Granules at 1.1 g / kg, 2.2 g / kg, and 4.4 g / kg, respectively, once daily. The model control group received an equal volume of normal saline. Drug administration continued for 10 days.

[0038] 2.4 Indicator Observation

[0039] The rats were observed during the treatment. The animals were killed 10 days after administration. The appendix was fixed in 10% formalin, embedded in paraffin, and sectioned. The inflammation of each layer of the appendix tissue was observed pathologically under a light microscope.

[0040] 3 Experimental results

[0041] In the model control group, the surface cells of the appendix mucosa of rats underwent obvious degeneration and necrosis, which was extensive and showed a severe acute inflammatory reaction. The submucosal layer had moderate congestion and edema, the muscular layer had a mild inflammatory reaction, the serosal layer had congestion, and the serosal surface had exudation and adhesion.

[0042] The appendix injuries of rats in the positive control group and the high-dose experimental group showed obvious repair phenomena, with a few glands in the appendix mucosa expanding; and the inflammatory cell response in each layer was significantly reduced.

[0043] In the medium-dose group, two rats still showed focal degeneration and necrosis of the appendix mucosal epithelium, and mild inflammatory reactions in all layers. The other eight rats were the same as those in the positive control group or the high-dose group.

[0044] In the low-dose group, 6 rats had focal degeneration or necrosis of the appendix mucosal epithelium, and the inflammatory cell reaction in each layer was moderate. In the other 4 rats, the appendix mucosal tissue recovered to a large extent, and the degree of inflammatory cell infiltration in each layer was mild.

[0045] Experimental Example 2 Study on the Effect of Danbai Granules on Acute Appendicitis in Rabbit Models

[0046] 1 Experimental Materials

[0047] 1.1 Experimental Animals

[0048] Thirty healthy rabbits (half male and half female, weighing 1.8-2.2 kg) were provided by the Pharmacology Center of Lunan Pharmaceutical Group (London Animal License No. SYXK(Lu)20180008). They were housed for one week prior to the experiment and had free access to food and water during the experiment, maintaining a 12-h circadian rhythm.

[0049] 1.2 Experimental Reagents

[0050] Penicillin sodium for injection, national medicine approval number H41020818, produced by Henan Xinxiang Huaxing Pharmaceutical Factory; metronidazole tablets, national medicine approval number H31020379, produced by Shanghai Xinyi Wanxiang Pharmaceutical Co., Ltd.; Danbai granules, national medicine approval number Z20090651, produced by Shandong Xinshidai Pharmaceutical Co., Ltd.

[0051] 2 Experimental methods

[0052] 2.1 Animal grouping

[0053] The experimental animals were randomly divided into 5 groups, namely model control group, positive control group, Danbai granule group, and integrated Chinese and Western medicine group; there were 6 animals in each group.

[0054] 2.2 Modeling method

[0055] Each rabbit was secured to an operating table, its skin prepared and disinfected with a drape. Local anesthesia was achieved by infiltration of the abdominal wall with 4 ml of 1% lidocaine. A 6-cm midline incision was made. The appendix was extracted by tracing the cecum, protecting the mesoappendix artery and vein. A No. 4 silk suture was passed through the mesentery at the base of the appendix, closely adhering to the appendix wall, to ligate the appendix. This completely obstructed the appendix cavity and ensured blood supply to the appendix artery and vein. The appendix was then returned to the abdominal cavity, and the abdomen was closed layer by layer.

[0056] 2.3 Administration

[0057] Drug administration began 24 hours after modeling. The appendectomy group underwent appendectomy. The positive control group received intramuscular injections of 400,000 units of penicillin sodium and 0.2 g of metronidazole twice daily. The integrated Chinese and Western medicine group received intramuscular injections of 400,000 units of penicillin sodium and 0.2 g of metronidazole, and Danbai Granules (1.2 g / kg) were administered orally. The model control group received an equal volume of normal saline. The positive control group and the integrated Chinese and Western medicine group received the drugs for 7 consecutive days. The Danbai Granule group received Danbai Granules (1.2 g / kg) orally for 10 consecutive days.

[0058] 2.4 Observation indicators

[0059] The mental state, diet, stool, rectal temperature, etc. of the rabbits in each group were observed; after death, an autopsy was performed to observe the abdominal appendix tissue. If the rabbits in each drug-treated group were still alive after two weeks of continuous observation, they were considered cured.

[0060] 3 Experimental results

[0061] The survival status of rabbits in each group is shown in Table 1.

[0062] Table 1 Comparison of different treatment methods in each group of rabbits

[0063]

[0064]

[0065] Rabbits in the model control group received no treatment and had persistent fever after surgery, with rectal temperature above 40°C and obvious abdominal distension. All of them died within 2-5 days after modeling. Autopsy revealed intra-abdominal pus, severe intra-abdominal tissue edema, and highly swollen and suppurative appendix. Four rabbits had appendicitis.

[0066] All 6 rats in the appendectomy group were cured. One day after the appendectomy, the body temperature began to drop and returned to normal within 3-5 days. The spirit gradually improved, the appetite increased, the abdominal distension disappeared, and the condition returned to preoperative state in about 1 week.

[0067] In the positive control group, two animals recovered, and four died. In the cured animals, body temperature began to decrease 3-4 days after modeling, returning to normal within about a week. Mental fatigue declined 2-3 days after modeling, but gradually improved, with increased appetite and decreased or absent abdominal distension, leading to substantial recovery after 7 days. The four animals that died died between 2 and 4 days after modeling. Autopsy revealed pus in the abdominal cavity, a visibly suppurated and swollen appendix, and perforated appendix in two animals.

[0068] In the Danbai Granule group, four animals recovered, while two died. Within one week, the cured animals' body temperatures returned to normal, their spirits gradually became more active, their abdominal distension significantly lessened, their stools became watery, and their food intake gradually returned to preoperative levels. The two animals that died died three or four days after modeling. Autopsies revealed a large amount of pus in the abdomen, a purulent and enlarged appendix, and adhesions to the surrounding intestine. One animal also had a perforated appendix.

[0069] In the integrated Chinese and Western medicine group, 5 animals were cured and 1 died. The cured animals' body temperature returned to normal within 5-8 days, their spirits gradually improved, their appetite increased, and their abdominal distension decreased and returned to preoperative levels. The one that died died on the third day after modeling with significant abdominal distension. An autopsy revealed intra-abdominal pus and severe appendicitis, but no appendicitis perforation was found.

[0070] The above experimental results show that Danbai Granules can relieve the symptoms of acute appendicitis, effectively treat acute appendicitis model rabbits, and reduce the dosage of antibiotics or avoid the use of antibiotics.

Claims

1. Use of Danbai Granules in the preparation of medicines for treating acute appendicitis.

2. The use according to claim 1, characterized in that Danbai granules are used as the sole active ingredient in preparing medicine for treating acute appendicitis.

3. The use according to claim 1, characterized in that Use of Danbai granules combined with antibiotics in the preparation of medicines for treating acute appendicitis.

4. The use according to claim 1, characterized in that The human dosage of Danbai Granules is 0.2-1.0g / kg / d.

5. The use according to claim 4, characterized in that The human dosage of Danbai Granules is 0.4-0.5g / kg / d.

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