Umbilical therapy composition and umbilical therapy preparation for preparing medicine for preventing and treating abdominal pain caused by intravenous drip of azithromycin in children and preparation method of umbilical therapy composition and umbilical therapy preparation

Abstract

The invention relates to the technical field of traditional Chinese medicines, and particularly discloses a navel therapy composition and a navel therapy preparation for preventing and treating abdominal pain caused by intravenous drip of azithromycin in children and a preparation method of the navel therapy composition and the navel therapy preparation. The technical key points are as follows: the fructus evodiae and the dysentery are combined according to a specific weight ratio, and are matched with pharmaceutic adjuvants such as a transdermal enhancer and an excipient to prepare special navel therapy dosage forms such as pills, cakes, patches and the like. According to the composition, by utilizing the characteristics that the Shenque acupoint (navel) epidermal cuticle is thin, the barrier function is weak, blood vessels are rich, and medicines are easy to disperse and absorb, adverse reactions such as gastrointestinal spasmodic pain, nausea and vomiting and the like caused by intravenous drip of azithromycin in children are effectively relieved through an administration mode of external application. Through clinical verification, the umbilical therapy preparation can remarkably reduce the incidence rate and severity score of stomachache, vomiting and diarrhea, and remarkably improve the treatment compliance of child patients.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine, more specifically, it relates to an umbilical therapy composition for preparing a medicine for preventing and treating abdominal pain caused by intravenous drip of azithromycin in children, an umbilical therapy preparation and a preparation method thereof. BACKGROUND

[0002] Azithromycin is a kind of macrolide antibiotic, which has good curative effect on respiratory tract infection (especially mycoplasma pneumonia) and skin and soft tissue infection in children. However, with the wide use of azithromycin, its adverse reactions are also increasing gradually. According to existing research reports, gastrointestinal reactions caused by azithromycin injection in children can reach as high as 63%, which accounts for the largest proportion in adverse reactions, not only increases the workload of pediatric clinical nursing, but also adds certain difficulty to pediatric nursing work, and is also the main reason for clinical drug withdrawal, affecting the treatment effect.

[0003] At present, there are more researches on western medicine methods for preventing and treating gastrointestinal reactions caused by azithromycin, mainly through oral drugs such as probiotics. Probiotics are live microorganisms that combine with the host epithelium to regulate the ecological balance of the intestinal tract, and can alleviate gastrointestinal discomfort symptoms to a certain extent, but the effect is often not very ideal, and the compliance of the patients is low.

[0004] Traditional Chinese medicine external treatment, especially umbilical therapy, provides a new idea for solving this problem. The Shenjue acupoint (navel) has thin skin, rich blood vessels and strong permeability, which is beneficial to drug absorption and can directly reach the viscera through meridians. Existing researches have confirmed that umbilical therapy has good effect on pediatric digestive tract diseases. Keleshia capsule is a kind of classic Chinese medicine, which is composed of Bai Zhi, Cangzhu, Shichangpu, Xiesheng, Bajiazha, Ebusunshicao, Zhuyazhao, Xionghuang, Dingshang, Niter, Bai' an, Bingpian, etc., which has the effects of detoxification, dispelling evil, regulating qi and stopping diarrhea, and is mainly used for the treatment of infectious and functional diarrhea in clinic. Traditionally, it is administered orally.

[0005] However, there is no any public report on the improvement of Keleshia capsule into a special dosage form for umbilical therapy, especially for preventing and relieving abdominal pain caused by intravenous drip of azithromycin in children. SUMMARY

[0006] The first purpose of the present application is to provide an umbilical therapy composition with synergistic effect and strong pertinence, which is specially used for preventing and treating abdominal pain caused by intravenous drip of azithromycin in children, has fast and significant effect, high safety, and can greatly improve the treatment compliance of children patients.

[0007] The second purpose of the present application is to provide an umbilical therapy preparation containing the above-mentioned umbilical therapy composition, which is suitable for relieving or preventing abdominal pain caused by intravenous drip of azithromycin through Shenjue acupoint administration.

[0008] The third object of the present application is to provide a preparation method of the umbilical therapy preparation, which is simple and easy to operate and suitable for clinical application.

[0009] To achieve the above object, the present application adopts the following technical solutions: In the first aspect, the present application provides an umbilical therapy composition for preventing and treating abdominal pain caused by intravenous infusion of azithromycin in children, which is composed of Evodia rutaecarpa and Keli Sha.

[0010] The Evodia rutaecarpa used in the present application is a powder prepared from the dried mature fruits of Evodia rutaecarpa of the Rutaceae family; and the Keli Sha is a powder of the contents of Keli Sha capsules, which retains all the components in the original formulation proportion.

[0011] Preferably, the weight ratio of the Evodia rutaecarpa to the Keli Sha is 1:5 to 1:1, and the further preferred ratio is 1:3 to 1:2. For example, 1 part of the Evodia rutaecarpa powder is mixed with 2 parts of the powder of the contents of Keli Sha capsules, or 1 part of the Evodia rutaecarpa powder is mixed with 3 parts of the powder of the contents of Keli Sha capsules. This ratio has been verified by experiments to significantly enhance the effect of penetration and absorption of the drug through the Shenjue acupoint, improve the regulation of the gastrointestinal smooth muscle, and relieve the intestinal spastic pain caused by intravenous infusion of azithromycin.

[0012] In the second aspect, the present application provides an umbilical therapy preparation made of the umbilical therapy composition, which is composed of the umbilical therapy composition and pharmaceutical excipients.

[0013] Preferably, the excipients include at least one of a transdermal enhancer, an excipient, and a humectant, wherein the transdermal enhancer is selected from azone or oleic acid, the excipient is vaseline or beeswax, and the humectant is glycerol. The addition of the above excipients helps to improve the adhesion and stability of the preparation and promote the transdermal absorption of the active ingredients.

[0014] Preferably, the umbilical therapy preparation is in the form of a pill, a cake, a powder, a patch, or a paste.

[0015] In the third aspect, the present application provides a preparation method of the umbilical therapy preparation, which includes the following steps: The Evodia rutaecarpa and the Keli Sha are mixed in the selected proportion, and at least one of a transdermal enhancer, an excipient, and a humectant is added. After stirring and mixing, a soft material is prepared, which is pressed into a pill by a pill press or molded into a cake, or coated on a medical dressing to prepare a patch.

[0016] Preferably, the Evodia rutaecarpa is a powder prepared from dried and crushed Evodia rutaecarpa medicinal materials and sieved to control the particle size at 80-120 mesh.

[0017] Preferably, the Keli Sha is a powder of the contents of Keli Sha capsules that meets the national drug standards and is commercially available.

[0018] In summary, the present application has the following advantages: (1) The present application creatively combines two drugs with different efficacy focuses, Evodia rutaecarpa and Klabion, into a new umbilical therapy composition, and the composition can produce a synergistic effect in preventing and treating azithromycin abdominal pain, which is significantly better than any single drug; (2) The composition is specifically designed for intravenous infusion of azithromycin, with spastic pain and nausea as the main features of the side effects, and the targeting is more specific; (3) The composition can be prepared as an umbilical therapy drug, and the mode of action is external umbilical therapy, which is non-invasive and painless, and solves the problem of oral administration for children, with high compliance; (4) The composition is a traditional Chinese medicine, and the external use further reduces the risk of adverse reactions. BRIEF DESCRIPTION OF DRAWINGS

[0019] Figure 1 Wong-Baker face pain score chart for evaluation of abdominal pain in children.

[0020] Figure 2 Digital assessment scale for children's abdominal pain evaluation. DETAILED DESCRIPTION

[0021] The embodiments of the present application are described below through specific specific examples, and those skilled in the art can easily understand other advantages and effects of the present application from the disclosure of the present specification. The present application can also be implemented or applied by other different specific embodiments, and the details in the specification can be modified or changed based on different views and applications without departing from the spirit of the present application.

[0022] In addition, it should be understood that one or more method steps mentioned in the present application does not exclude that there can be other method steps before and after the combination step or other method steps can be inserted between the explicitly mentioned steps, unless otherwise stated. Moreover, unless otherwise stated, the numbering of each method step is only a convenient tool to identify each method step, and is not a limitation on the arrangement order of each method step or a limitation on the scope of the present application, and changes or adjustments of the relative relationship without substantial changes in technical content are also considered as the scope of the present application.

[0023] If the specific conditions of the experiments are not specified in the examples, they are usually in accordance with the conventional conditions in the art, or in accordance with the conditions recommended by the reagent company; The materials, reagents, etc. used in the examples can be obtained by commercial means, unless otherwise specified.

[0024] Example 1 Preparation of umbilical therapy composition Take Evodia rutaecarpa medicinal material, dry it, pulverize it with a pulverizer, sieve it, and retain the fine powder through an 80-120 mesh sieve to obtain Evodia rutaecarpa powder; Take the contents of Kelisha capsules (Zhejiang Suanke Pharmaceutical Co., Ltd., National Drug Approval Number Z20163025) to obtain Kelisha capsule contents powder; Mix the powder of Evodia rutaecarpa with the powder of the contents of Kelisha capsules at a mass ratio of 1:3 to obtain a traditional Chinese medicine compound powder, which is the umbilical therapy composition.

[0025] Example 2 Preparation of Umbilical Therapy Pill Formulation The umbilical therapy composition prepared in Example 1 was mixed with petroleum jelly to form a smooth, non-sticky soft material. The soft material was then divided into pills weighing 2 grams each. Each pill contained 0.3g of the contents of the Keli Sha capsule and 0.1g of Evodia rutaecarpa powder.

[0026] Comparative Example 1: Preparation of Evodia rutaecarpa umbilical therapy pills The preparation method is the same as in Example 2, except that only Evodia rutaecarpa powder is used, and the powder containing the contents of Kelisha capsules is not added. Each of the prepared Evodia rutaecarpa umbilical therapy pills weighs 2g and contains 0.4g of Evodia rutaecarpa powder.

[0027] Comparative Example 2: Preparation of Dysentery Umbilical Therapy Pills The preparation method is the same as in Example 2, except that only the powder containing the contents of Kelisha capsules is used, and no Evodia rutaecarpa powder is added. Each Kelisha umbilical therapy pill weighs 2g and contains 0.4g of the powder containing the contents of Kelisha capsules.

[0028] Clinical efficacy observation trial 1. Selection of test subjects: 290 children aged 3-11 years who were hospitalized in the pediatric department of a secondary public hospital in Yangpu District, Shanghai from May 2023 to May 2024, and who were diagnosed with Mycoplasma pneumoniae pneumonia by Western medicine and were prescribed intravenous azithromycin, were randomly divided into five groups: control group, oral probiotic group, Evodia rutaecarpa umbilical therapy group, Keli Sha umbilical therapy group, and compound preparation umbilical therapy group, with 58 cases in each group.

[0029] The enrolled children were given 10 mg / kg of azithromycin (Pfizer Pharmaceuticals, National Drug Approval Number J20140073) in 5% glucose injection to prepare a concentration of 1-2 mg / ml, which was then administered intravenously once a day for 5 consecutive days.

[0030] 2. Grouping Control group: Received only routine intravenous azithromycin treatment and routine nursing care.

[0031] Oral probiotic group: In addition to the treatment of the control group, the group was given oral Bifidobacterium triple live bacteria capsules (Xinyi Pharmaceutical, National Drug Approval Number S10950032) twice a day for 5 consecutive days.

[0032] Evodia rutaecarpa umbilical therapy group: In addition to the control group, the group received Evodia rutaecarpa umbilical therapy pills prepared in Comparative Example 1 30 minutes before the start of intravenous infusion of azithromycin. The pills were removed 1 hour after the azithromycin infusion was completed, and the skin was cleaned. The treatment was administered once daily for 5 consecutive days.

[0033] Keli Sha Umbilical Therapy Group: In addition to the control group, Keli Sha umbilical therapy pills prepared in Comparative Example 2 were administered 30 minutes before the start of intravenous infusion of azithromycin. The pills were removed 1 hour after the azithromycin infusion was completed, and the skin was cleaned. The treatment was performed once daily for 5 consecutive days.

[0034] Compound preparation umbilical therapy group: In addition to the control group, the umbilical therapy pill preparation prepared in Example 2 was administered 30 minutes before the start of intravenous infusion of azithromycin for umbilical therapy. The umbilical therapy pill was removed 1 hour after the azithromycin infusion was completed, and the skin was cleaned. Once a day, for 5 consecutive days of umbilical therapy.

[0035] 3. Evaluation Criteria 3.1 Evaluation of vomiting Vomiting is defined as the rapid expulsion of stomach contents through the mouth in a child. During intravenous azithromycin treatment, any occurrence of vomiting is considered a vomiting reaction; the absence of vomiting during intravenous azithromycin treatment is considered a non-vomiting reaction. The vomiting incidence results are shown in Table 1.

[0036] During intravenous azithromycin treatment, the total score of vomiting symptoms was calculated using the WHO vomiting grading system. The scoring results are shown in Table 2. A higher score indicates a more severe degree of vomiting. Grade I (0 points): No vomiting symptoms; Grade II (1-3 points): Vomiting 0-2 times; Grade III (4-7 points): Vomiting 3-5 times; Grade IV (8-10 points): Vomiting more than 6 times.

[0037] 3.2 Diarrhea Assessment Diarrhea is defined as three or more bowel movements within 24 hours, with stools that are loose, watery, mucoid, or bloody. During intravenous azithromycin treatment, the presence of diarrhea is considered a diarrheal reaction; conversely, the absence of diarrhea is considered a negative diarrheal reaction. The incidence of diarrhea is shown in Table 1.

[0038] The total score of diarrhea symptoms was calculated during the intravenous infusion of azithromycin treatment, and the results are shown in Table 2. The higher the score, the more severe the diarrhea: Grade I (0 points): 0-3 times of defecation per day, with dry or thin stool; Grade II (1-3 points): 0-3 times of defecation per day, with soft or watery stool; Grade III (4-7 points): 4-5 times of defecation per day, with watery stool; Grade IV (8-10 points): 6 times or more of defecation per day, with watery or purulent stool.

[0039] 3.3, Abdominal pain evaluation Abdominal pain was determined when the child had abdominal pain below the stomach, on both sides of the navel and above the pubic bone. During the intravenous infusion of azithromycin treatment, the child was considered to have abdominal pain if he had abdominal pain symptoms; during the intravenous infusion of azithromycin treatment, the child was considered not to have abdominal pain if he never had abdominal pain symptoms. The incidence of abdominal pain is shown in Table 1.

[0040] During the intravenous infusion of azithromycin treatment, the total score of abdominal pain symptoms was calculated, and the results are shown in Table 2. Children aged 3-8 years old usually can indicate the location of pain, but cannot clearly express the intensity of pain, so Wong-Bakerr facial pain score was used, see Appendix Figure 1 , the degree of pain is 0-10, the larger the number, the more severe the pain. Children aged 8-11 years old usually can clearly express the intensity of pain, so NRS numerical rating scale was used, see Appendix Figure 2 , the test children recorded the corresponding number on the evaluation table according to their own pain perception, the degree of pain was 0-10, the larger the number, the more severe the pain.

[0041] 3.4, Compliance evaluation During the intravenous infusion of azithromycin, if the child did not cry, was not irritable and refused to receive infusion treatment, it was considered to be completely compliant; if the child was irritable, did not cooperate with infusion treatment, needed a long time to calm down, or refused to continue infusion, it was considered to be not completely compliant. The test results are shown in Table 3.

[0042] 4, Evaluation results Table 1 Comparison of gastrointestinal reaction incidence in different groups of children [example (%)] Note: The same column data with different lowercase letters indicates significant difference between groups, with statistical significance (P<0.05).

[0043] Results showed that the overall difference in the incidence of nausea, vomiting, abdominal pain and diarrhea in each group of children was statistically significant (p<0.05). Compared with the control group, oral probiotics group can significantly reduce the incidence of all adverse reactions (p<0.05), the incidence of gastrointestinal reactions in children treated with Evodia umbilical therapy or Kechiacha umbilical therapy alone was lower than that in the control group, but the difference did not reach a significant level (p>0.05). The umbilical therapy group of compound preparation showed the best effect in each index, which was significantly lower than that in other groups (p<0.05), indicating that it had better clinical value in relieving gastrointestinal adverse reactions related to intravenous infusion of azithromycin in children.

[0044] Table 2 Comparison of gastrointestinal symptom scores in children in different groups ±s] Note: The same column data with different lowercase letters indicates significant difference between groups, with statistical significance (P<0.05).

[0045] Results showed that compared with the control group, oral probiotics group can significantly reduce the score of all three adverse reactions (P<0.05); Evodia umbilical therapy group and Kechiacha umbilical therapy group had a decreasing trend in each score, but the difference did not reach statistical significance (P>0.05). The umbilical therapy group of compound preparation was significantly lower than other groups in the scores of vomiting, diarrhea and abdominal pain (P<0.05), and the abdominal pain score was zero, indicating that it had better efficacy in improving gastrointestinal reactions related to intravenous infusion of azithromycin.

[0046] Table 3 Comparison of treatment compliance in children in different groups [Example (%)] Note: The same column data with different lowercase letters indicates significant difference between groups, with statistical significance (P<0.05).

[0047] Results showed that the overall difference in treatment compliance rate of each group of children was statistically significant (P<0.05). Compared with the control group, oral probiotics group can significantly improve the treatment compliance rate (P<0.05); the compliance rate of Evodia umbilical therapy group and Kechiacha umbilical therapy group was higher than that of the control group, but the difference did not reach statistical significance (P>0.05); the complete compliance rate of the umbilical therapy group of compound preparation was 93.1%, which was significantly higher than that of other groups (P<0.05), indicating that this therapy can greatly improve the treatment compliance of children, which should be closely related to its effective relief of abdominal pain and other gastrointestinal adverse reactions.

[0048] The above merely describes preferred embodiments of the present application, and is not intended to limit the present application in any form or in essence. It should be noted that those skilled in the art can make some improvements and supplements without departing from the method of the present application, and these improvements and supplements should also be considered as the protection scope of the present application. For those skilled in the art, some slight changes, modifications and equivalent changes made by using the disclosed technical content without departing from the spirit and scope of the present application are equivalent embodiments of the present application; meanwhile, any equivalent changes, modifications and evolution made according to the essential technology of the present application to the above embodiments are still within the scope of the technical solutions of the present application.

Claims

1. A navel therapy composition for preparing a medicine for preventing and treating abdominal pain caused by intravenous drip of azithromycin in children, characterized in that, The omni-therapeutic composition consists of Evodia rutaecarpa and Krimihas.

2. The omitherapy composition of claim 1, wherein The weight ratio of Evodia rutaecarpa to Krimihas is 1:5 to 1:

1.

3. The ometherapy composition of claim 2, wherein, The weight ratio of Evodia rutaecarpa to Krimihas is 1:3 to 1:

2.

4. An omni-therapeutic formulation, characterized in that, The omni-therapeutic preparation consists of the omni-therapeutic composition of any one of claims 1-3 and pharmaceutically acceptable excipients.

5. The ometherapeutic preparation according to claim 4, characterized in that, The pharmaceutically acceptable excipients include at least one of transdermal enhancer, excipient and humectant.

6. The omni-therapeutic preparation according to claim 4, characterized in that, The dosage form of the omni-therapeutic preparation is pill, cake, powder, patch or ointment.

7. A method of preparing the umbilical therapy preparation according to any one of claims 4-6, characterized in that, The method comprises the following steps: Evodia rutaecarpa and Krimihas are mixed in selected proportions, at least one of transdermal enhancer, excipient and humectant is added, and the mixture is stirred and mixed to form a soft material, which is pressed into pills or cakes by a pill press or coated on a medical dressing to prepare a patch.

8. The method for preparing the umbilical therapy preparation according to claim 7, characterized in that, The Evodia rutaecarpa is a powder of Evodia rutaecarpa medicinal material, which is dried, crushed, sieved and controlled to have a particle size of 80-120 mesh.

9. The method for preparing the umbilical therapy preparation according to claim 7, characterized in that, The Krimihas is a powder of Krimihas capsule content.

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