Application of polyprazineb in gastrointestinal diseases
- Categories:Stomach healthy
- Time of issue:2021-01-19
Application of polyprazineb in gastrointestinal diseases
- Categories:Stomach healthy
- Time of issue:2021-01-19
Polyprezinc is a kind of chelating compound composed of zinc ion and L-carnosine, which has the dual mechanism of protection and repair. Among them, zinc is an essential trace element for human body, which exists in meat, eggs, shellfish, cheese and beans. At the same time, zinc also participates in the synthesis of more than 300 enzymes in human body. These enzymes are very important for cell repair, especially for epithelial cells and epidermal cells. It is necessary for wound healing of skin, connective tissue and intestinal wall. Most importantly, zinc can effectively repair the damaged gastrointestinal mucosa. Zinc deficiency caused by diet, genetics or other reasons can lead to diseases, such as growth retardation, skin symptoms and taste disorders.
Carnosine is a dipeptide composed of β - alanine and L-histidine, which mainly exists in muscle. Studies have shown that carnosine has membrane stability and antioxidant activity, and also has benefits for cancer and diabetes. Most importantly, carnosine is a chelator of metal ions, which can be used as a good carrier to participate in chemical reactions. Carnosine in polyprazeb is the most ideal carrier of zinc, which can efficiently transfer zinc into the organism and play the greatest pharmacological role. The two have a good synergistic effect.
Mechanism of action of 1-polyprazineb
1.1 anti inflammatory
Studies have shown that ppz can repair gastric mucosal injury and accelerate its healing. The main mechanism of action is considered to be related to the anti-inflammatory effect of pprezeb. A study of ethanol induced gastric injury model in rats showed that the inflammatory cytokines (IL-1 β, IL-8, IL-6 and TNF - α) of animals treated with ppz decreased in a dose-dependent manner, indicating that ppz can reduce the expression of inflammatory cytokines and play an anti-inflammatory role. NF KB is one of the main transcription factors that regulate the expression of many genes in inflammation and immune response. In some in vitro and animal model experiments, it has been confirmed that polyprazeb can inhibit the activity of NF KB and reduce the inflammatory response.
In a 12 week study, subjects aged 65-85 years with low plasma zinc levels were randomized to receive either polyprazeb or placebo. Compared with baseline, the plasma iron reduction capacity and erythrocyte superoxide dismutase (esod) activity were higher in the zinc group; in addition, another study showed that the activities of antioxidant markers (SOD-1, Sod-2, HO-1, prx-1 and prx-v) were significantly higher in the zinc group than in the treatment group. These results indicate that ppz can protect gastric mucosa from damage by increasing the activity of oxygen free radical scavenging enzymes and scavenging free radicals.
1.3 multiple repair
Studies have shown that ppz can up regulate the expression of growth factors (IGF, EGF, VEGF, NGF, PDGF), and then promote angiogenesis and ulcer healing. At the same time, some studies have found that other mechanisms of the beneficial effect of ppz are up regulating the expression of heat shock protein (HSP).
An in vitro study examined the effect of polyprazeb on cell activity in the early (promoting migration and recovery) and late (promoting proliferation) healing stages of colon cells. The results showed that polyprazeb promoted cell migration and proliferation in a dose-dependent manner and could stimulate early and late intestinal repair. This conclusion is applicable to other epithelial cells.
Oral mucositis is a common complication of radiotherapy and chemotherapy, which occurs in almost all patients with head and neck cancer receiving radiotherapy. It is characterized by severe pain, dysphagia, loss of appetite, malnutrition and dehydration, which seriously damages the quality of life of patients and may lead to prolonged hospital stay or early cessation of treatment. Therefore, the prevention of mucositis may improve the prognosis and reduce the length of hospital stay .
A prospective study to evaluate the feasibility and effectiveness of polyprazeb in the treatment of radiation mucositis in patients with head and neck cancer during radiotherapy. Grade 3 mucositis was well tolerated in 29% vs 40% (based on mucosal examination) and 39.3% vs 60.7% (based on self-reported symptoms) of patients who received or did not receive ppz. The above data can show the important role of polyprazeb in mucositis.
In recent years, it has been reported that ppz can effectively prevent oral mucositis caused by radiotherapy for head and neck cancer, high-dose chemotherapy and radiotherapy before hematopoietic stem cell transplantation. In patients receiving high-dose chemotherapy for hematopoietic stem cell transplantation, the severity of oral mucositis was significantly reduced by 13%, and the use of pain drugs was also reduced by 13%. Another study showed that ppz can not only effectively prevent oral mucositis caused by radiotherapy and chemotherapy for head and neck cancer, but also effectively prevent oral mucositis caused by high-dose radiotherapy and chemotherapy after HSCT.
In 423 patients with oral mucosal injury due to cancer treatment, ppz can effectively improve oral mucosal injury. The success rates of stomatitis prevention, symptom improvement, pain prevention and symptom improvement were 68.5%, 84.4%, 75.4% and 76.7% in chemotherapy group (n = 280), 32.7%, 64.5%, 45.5% and 73.5% in chemoradiotherapy group (n = 95) and 29.6%, 60.0%, 40.7% and 68.6% in radiotherapy group respectively.
In addition, ppz can also prevent esophagitis caused by complications of radiotherapy and chemotherapy. A study of patients with non-small cell lung cancer treated with polyprazeb showed that polyprazeb significantly reduced the incidence of grade 2 radiation esophagitis (HR, 0.397; 95% CI, 0.160-0.990; P = 0.047), and delayed the incidence of grade 2 radiation esophagitis.
3 taste function
Taste disorders are very common, usually associated with oral mucositis and chemoradiotherapy, which are often ignored because they are not serious and life-threatening. However, taste disorders can seriously affect the quality of life of patients with head and neck cancer radiotherapy, affect the nutritional intake of patients, and indirectly affect the prognosis of more serious diseases.
Taste buds contain enzymes that need zinc, which play an important role in taste function. Some studies have shown that zinc supplementation can improve taste in patients with taste disorders that have nothing to do with cancer. In a randomized, double-blind, placebo-controlled trial, the effect of ppz on taste disorders was evaluated. The results showed that ppz could significantly improve the taste function of patients, and serum zinc increased in a dose-dependent manner with good safety. Another study evaluated the efficacy of polyprazeb in 40 patients with taste disorders. The two groups were treated with polyprazeb. The results showed that the symptoms of the two groups were significantly improved.
In a single center retrospective study, patients with grade 2 taste disorder caused by chemotherapy were given polyprazine daily until symptoms disappeared, while the control group was given gargle of Cymbidium. The results showed that ppz could significantly shorten the recovery time (HR 1.778; 95% CI = 1.275.2.280; P = 0.019). Multiple regression analysis showed that pancreatic cancer and the use of fluorouracil increased the risk of developing grade 2 taste disorders, which was probably due to the pancreatic secretion and zinc absorption.
Intestinal mucosal integrity
In a randomized, controlled, double-blind study, 258 subjects with gastric ulcer were randomly divided into two groups and treated for 8 weeks. At 4 weeks, the improvement rate of symptoms was 61% in the pprezeb group and 61.5% in the cetrolate group. At 8 weeks, the improvement was 75% in the pprezeb group and 72% in the cetrate group. The endoscopic cure rates were 26.3% and 16.2% at 4 weeks, 60.4% and 46.2% at 8 weeks. This suggests that compared with the previous mucosal protective agent cetroxil, polyprazeb can better relieve symptoms and improve gastric ulcer.
In the rat model of ethanol induced gastric injury, ppz can reduce the gastric ulcer index and show a significant ulcer healing effect similar to rebamipide. Similarly, in aspirin induced gastroduodenal injury animal model, compared with the control, polyprazeb has significant ulcer healing effect. In addition, a study of acetic acid-induced gastric injury in rats showed that compared with the control group, polyprazeb showed significant anti ulcer and healing effects. These effects may be attributed to the anti-inflammatory and antioxidant functions of ppz.
In vitro studies have shown that ppz can stimulate cell migration and proliferation, reduce gastric and small intestinal mucosal damage. In vivo studies have shown that ppz can reduce gastric and small intestinal mucosal damage. In a cross-over study of 10 healthy subjects, the changes of intestinal permeability before and after indomethacin treatment were compared with those after zinc or placebo treatment. The results showed that polyprazeb reduced the increase of intestinal permeability caused by indomethacin.
Due to short-term or long-term use of drugs, some morphological and functional changes of small intestine and large intestine are caused, and then colitis is caused, which is a common side effect of many drugs. Gastrointestinal adverse reactions, such as diarrhea and constipation, are usually associated with the use of non steroidal anti-inflammatory drugs (NSAIDs) and antibiotics. In fact, up to 70% of NSAIDs users have intestinal mucosal lesions, such as lesions, erosion, and even ulcers. Studies have shown that the anti-inflammatory and antioxidant properties of ppz and the ability to up regulate HSP can prevent the mucosal injury caused by NSAIDs.
In recent years, the eradication of Helicobacter pylori (HP) has attracted people's attention. Drugs that can improve the eradication rate of HP are of great significance. The results of phase IV clinical trial of raleson (polyprazeb granules) showed that the HP eradication rate of raleson combined with triple therapy was significantly higher than that of conventional triple therapy, and the difference of HP eradication rate was increased by 19.7% (Fig. 1), and there was no significant difference in the incidence of adverse reactions. The symptoms of abdominal pain, acid regurgitation, belching, heartburn, abdominal distension, nausea and vomiting were significantly improved (P < 0.0001), and gastrointestinal symptoms were significantly improved.
Figure 1 HP eradication rate in ITT and PP population
Arm a: traditional triple therapy + polyprazineb 75mg; arm B: traditional triple therapy + polyprazineb 150mg; arm C: Omeprazole + amoxicillin + clarithromycin (traditional triple therapy).
Pressure ulcer (PUs) is a common and expensive disease, especially for bedridden patients. However, in a randomized controlled trial, 42 patients with stage II to IV PU were divided into three groups. According to the pressure ulcer healing score (push), the improvement in carnosine group (1.6 ± 0.2, P = 0.02) and polyprazine group (1.8 ± 0.2, P = 0.009) was significantly higher than that in the control group (0.8 ± 0.2). Another study showed that push improved significantly from 8.1 [95% CI, 6.0-10.3] at baseline to - 1.4 [- 4.0-1.1] at 8 weeks (P < 0.001). One week later, there was significant difference compared with baseline (P < 0.05). The average improvement of push was 2.0 points per week. Eleven patients were cured within 8 weeks, and none of them quit. The serum zinc level increased significantly (P < 0.001). This also fully shows the effectiveness and good tolerance of polyprazineb for pus.
The metabolism of trace elements in patients with chronic liver disease is impaired, especially high levels of iron and copper, low levels of zinc, selenium, phosphorus, calcium and magnesium. It is reported that zinc supplementation can improve the response of patients with refractory chronic hepatitis C to interferon therapy. In a study, 12 patients with chronic hepatitis C were treated with pegylated interferon-2b combined with ribavirin for 48 weeks, and serum transaminase activity (ALT) was significantly decreased (n = 12). Ppz can reduce the concentration of plasma thiobarbituric acid reactants (TBARS) and prevent the decrease of erythrocyte polyunsaturated fatty acids (PUFA). Ppz can provide antioxidant protection for patients with chronic hepatitis undergoing treatment. A study was conducted to investigate the effects of polyprazeb on hepatic inflammatory activity and fibrosis in patients with hepatitis C virus (HCV) and chronic liver disease (CLD). The results show that ppz can reduce liver inflammation in patients with HCV related CLD through antioxidant effect, thus preventing iron induced free radical activity.
Zinc administration may lead to copper deficiency because high doses of zinc inhibit copper absorption. However, polyprazeb contains 22% zinc and 78% carnosine, and the content of zinc is about 15mg, which is not a high dose in the range of safe daily intake. Moreover, zinc and carnosine in polyprazeb were labeled by isotope tracing method. The results showed that carnosine was mainly excreted in the form of gaseous CO2, and 85% of zinc was excreted in the form of feces and absorbed about 11%, indicating that zinc in polyprazeb was safe and no accumulation; moreover, the content of zinc in urine was only 0.3%, indicating that zinc in polyprazeb was basically not metabolized through the kidney, and zinc in light urine was not metabolized through the kidney Moderate renal insufficiency can be taken normally without increasing or decreasing the dosage.
This article reviews the application of polyprazeb on gastrointestinal mucosa, and its benefits for oral mucositis, taste disorders, pressure ulcers and liver caused by radiotherapy and chemotherapy. It fully proves that polyprazeb is the first choice of mucosal protective agent for patients with gastrointestinal mucosal injury and radiotherapy and chemotherapy.
Polyprazine granules, L-carnosine and zinc chelator, are the classic representative of Japanese mucosal protective drugs, and are widely used in clinical treatment in many countries around the world. Its safety and effectiveness have been fully verified by millions of patients with gastrointestinal mucosal injury. As the first R & D enterprise of "jupri zinc granules" in China, Jilin Province Boda Weiye successfully completed the phase III registered clinical study in 2009 and was approved to be listed in 2012, with the trade name of Rui Lai Sheng. In 2013, the national multi center clinical research was launched, with a total of 11 authoritative research centers in China, which fully verified the effectiveness of Raleigh combined with triple therapy in eradicating HP, and can significantly improve gastrointestinal symptoms, with good safety and tolerance.
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