A birch bark extract solubilized preparation for preventing and treating radiation enteritis and a preparation method thereof

Abstract

This invention discloses a birch bark extract solubilizing formulation for the prevention and treatment of radiation enteritis and its preparation method, belonging to the field of pharmaceutical technology. The formulation includes birch bark extract, ethanol, and water. Poloxamer F68 is used as the solubilizing carrier, and the mass ratio of birch bark extract to poloxamer F68 is 1:(5-15). The solubilizing formulation is prepared through steps of ethanol co-dissolution, ultrasonic treatment, rotary evaporation to remove alcohol, and resolubilization with water. This invention effectively solves the technical bottlenecks of poor water solubility, insufficient dispersibility, and inadequate storage stability of birch bark extract. The prepared formulation is uniform and stable, significantly reducing the damage to the body caused by radiation enteritis, inhibiting intestinal inflammatory responses, and repairing the intestinal mucosal barrier. It can be used to prepare drugs for the prevention and treatment of radiation enteritis. Its preparation process is simple and controllable, with high pharmaceutical safety, and is suitable for industrial production.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a birch bark extract solubilizing preparation for the prevention and treatment of radiation enteritis and its preparation method. Background Technology

[0002] Radiation enteritis (RE) is one of the most common dose-limiting complications in patients with abdominopelvic malignancies undergoing radiotherapy. It is particularly prevalent during radiotherapy for cervical, rectal, and prostate cancers, with a clinical incidence exceeding 50%. Ionizing radiation can directly damage the DNA of intestinal mucosal epithelial cells and induce the production of large amounts of reactive oxygen species, triggering a cascade of intestinal inflammation, destruction of intestinal crypt structures, loss of mucosal barrier integrity, and abnormally increased intestinal permeability. Ultimately, this leads to irreversible pathological changes such as diarrhea, rectal bleeding, abdominal pain, progressive weight loss, intestinal mucosal ulceration, and even intestinal fibrosis. Radiation enteritis not only severely reduces patients' quality of life but also often forces the interruption of radiotherapy, directly impacting local tumor control rates and long-term patient survival. Currently, safe and effective targeted drugs for prevention and treatment are still lacking in clinical practice.

[0003] Current clinical interventions for radiation enteritis primarily focus on symptomatic and supportive treatment. Core protocols include antidiarrheal therapy, nutritional support, anti-infection treatment, mucosal protection, and non-specific anti-inflammatory therapy. However, existing protocols only alleviate clinical symptoms and cannot target the core pathological processes such as radiation-induced intestinal mucosal barrier damage and inflammatory homeostasis imbalance, making it difficult to reverse disease progression. While some amino acid preparations, steroidal anti-inflammatory drugs, and natural products have shown some intestinal protective effects in animal experiments, they generally suffer from limited efficacy, insufficient specificity of indications, poor long-term safety, and unsatisfactory formulation stability, failing to meet the actual clinical needs for the prevention and treatment of radiation enteritis.

[0004] Birch bark is from the birch family plant, birch (Birch spp.) Betula platyphylla The dried, soft bark of *Birch bark* (*Such.*) has a long history of medicinal use in traditional Chinese medicine, where it is used to clear heat and dampness, detoxify, and relieve itching. Modern pharmacological studies have confirmed that birch bark extract is rich in triterpenoid active ingredients such as betulinol and betulinic acid, exhibiting significant anti-inflammatory, antioxidant, immunomodulatory, and mucosal protective activities, showing promising application potential in the prevention and treatment of inflammatory bowel disease. Previous studies have shown that birch bark extract can significantly improve pathological changes in radiation enteritis models, such as weight loss, increased disease activity index, colonic shortening, and tissue inflammatory infiltration, making it a high-quality natural candidate drug for the prevention and treatment of radiation enteritis.

[0005] However, birch bark extract faces a critical formulation bottleneck in pharmaceutical development: its core active ingredient is a highly lipid-soluble triterpenoid compound with extremely low solubility in water. Direct dispersion in water results in rapid precipitation, leading to poor dispersibility, insufficient drug loading, and poor storage stability. This prevents the achievement of effective in vivo concentrations, severely limiting its stable efficacy. For radiation enteritis prevention and treatment agents requiring oral administration and local gastrointestinal action, the inability of the active ingredient to form a stable and homogeneous aqueous dispersion directly results in abnormal release in the gastrointestinal tract, low bioavailability, and poor reproducibility of efficacy, failing to meet clinical administration requirements.

[0006] For poorly soluble natural products, existing technologies often employ solubilization methods such as organic solvents, nonionic surfactants, cyclodextrin inclusion complexes, and solid dispersions. However, each of these technologies has significant limitations: while organic solvents such as ethanol can achieve short-term dissolution, their high volatility makes it impossible to construct a stable aqueous drug delivery system, and they are highly irritating when taken orally; although dimethyl sulfoxide (DMSO) has strong solubility, the active ingredients are prone to precipitation after dilution or standing, and it also exhibits cytotoxicity, resulting in poor pharmaceutical safety; conventional excipient complex systems such as sodium carboxymethyl cellulose (CMC-Na) and Tween-80 have limited solubilization capabilities for birch bark extracts, and precipitation easily occurs after standing, making the system stability unsuitable for pharmaceutical applications.

[0007] To date, existing technologies lack a systematic formulation development plan for the prevention and treatment of radiation enteritis using birch bark extract, failing to simultaneously achieve the three core objectives: firstly, to efficiently improve the water solubility and storage stability of birch bark extract; secondly, to achieve a controllable high drug loading to meet the dosage requirements for oral administration; and thirdly, to ensure the stable efficacy of the formulation in vivo for the prevention and treatment of radiation enteritis. Therefore, developing a formulation system adapted to the characteristics of birch bark extract, possessing high solubility, excellent stability, and clearly defined preventive and therapeutic activity, is crucial for its clinical translation.

[0008] Poloxamer F68 is a pharmaceutical-grade nonionic surfactant with excellent biocompatibility and safety. It is listed in the pharmacopoeias of China, the United States, Europe, and other countries, and is widely used in pharmaceutical systems such as injections and oral formulations. It can self-assemble into micelles in water, encapsulating lipophilic drugs through a hydrophobic core and stably dispersing them in the aqueous phase through a hydrophilic shell, thereby significantly improving the apparent solubility, dispersion uniformity, and storage stability of poorly soluble drugs. Based on this, this invention uses poloxamer F68 as the core solubilizing carrier to construct a solubilizing formulation system adapted to birch bark extract, completely solving the technical bottleneck of poor water solubility and limited application. Simultaneously, it verifies its clear preventive and therapeutic effect on radiation enteritis, providing a safe and effective new drug candidate for clinical use. Summary of the Invention

[0009] The purpose of this invention is to provide a birch bark extract solubilizing preparation for the prevention and treatment of radiation enteritis and its preparation method, so as to solve the problems mentioned in the background art.

[0010] To achieve the above objectives, the present invention provides the following technical solution: In a first aspect, the present invention provides a birch bark extract solubilizing preparation for the prevention and treatment of radiation enteritis, comprising birch bark extract, ethanol and water, wherein the solubilizing preparation uses poloxamer F68 as a solubilizing carrier, and the mass ratio of birch bark extract to poloxamer F68 is 1:(5-15). The solubilizing preparation is prepared by steps of co-dissolving in ethanol, ultrasonic treatment, rotary evaporation to remove alcohol and redissolving in water.

[0011] Furthermore, the formulation showed no visible precipitation or stratification when placed at room temperature in the dark for 72 hours.

[0012] Furthermore, the mass concentration of the birch bark extract in the preparation is 10–30 mg / mL.

[0013] Furthermore, the rotary evaporation process is carried out at a temperature of 35–45°C.

[0014] Furthermore, the solubilizing agent is an oral liquid formulation.

[0015] Secondly, the present invention provides a method for preparing the above-mentioned birch bark extract solubilizing preparation for preventing and treating radiation enteritis, comprising the following steps: S1 Weigh out birch bark extract and poloxamer F68 according to the preset mass ratio; S2. Poloxamer F68 was added to ethanol and sonicated until completely dissolved. Then, birch bark extract was added and mixed evenly. The mixture was sonicated again to obtain a homogeneous and transparent mixture. S3 The homogeneous mixture obtained in step S2 is subjected to rotary evaporation at 35-45°C to completely remove ethanol, resulting in a solid dispersion of birch bark extract and poloxamer F68. S4. Add purified water to the solid dispersion obtained in step S3, and stir or shake until completely dissolved to obtain a homogeneous and stable birch bark extract solubilization preparation.

[0016] Furthermore, the ethanol mentioned in step S2 is anhydrous ethanol.

[0017] Furthermore, the total duration of the ultrasonic treatment in step S2 is 5 to 30 minutes.

[0018] Thirdly, the present invention provides the application of the above-mentioned birch bark extract solubilizing preparation in the preparation of a drug for preventing and treating radiation enteritis.

[0019] Furthermore, the drug is used to achieve at least one of the following effects: (1) Reduce weight loss, diarrhea, hematochezia, shortening of the colon and pathological damage to colon tissue caused by radiation enteritis; (2) Reduce the expression level of at least one of the pro-inflammatory factors TNF-α, IL-1β and IL-6, while increasing the expression level of the anti-inflammatory factor IL-10, thereby inhibiting the intestinal inflammatory cascade.

[0020] Furthermore, the drug is an oral preparation, including but not limited to oral liquids, suspensions, granules, and capsules, preferably an oral liquid preparation.

[0021] Compared with the prior art, the beneficial effects of the present invention are: This invention uses poloxamer F68 as a solubilizing carrier and employs a process of ethanol co-solubilization-rotary evaporation-water resolubilization to precisely encapsulate the lipid-soluble triterpenoid active ingredients in birch bark extract within the hydrophobic core of poloxamer micelles, significantly improving its apparent solubility in the aqueous phase. The resulting formulation is a homogeneous and transparent liquid that shows no precipitation or stratification after 72 hours of storage at room temperature in the dark. Accelerated stability testing shows a content retention rate of over 95% after 30 days. This overcomes the shortcomings of existing solubilization systems, such as easy precipitation and poor stability, and solves the core problem that limits the clinical application of birch bark extract due to its poor water solubility. The preparation method of this invention does not require complex equipment such as high-pressure homogenization and nanoparticle preparation. It can be completed using only conventional pharmaceutical processes such as ultrasound and rotary evaporation. The process parameters are controllable and the batch stability is good. The anhydrous ethanol used in the preparation process can be completely removed by rotary evaporation, leaving no toxic solvent residue. The excipient poloxamer F68 used is a pharmaceutical-grade excipient listed in the pharmacopoeia. It has good biocompatibility, high oral safety, and fully meets the requirements for the development of pharmaceutical preparations. It is easy to achieve industrial-scale production. This invention is the first to use a birch bark extract-based solubilized formulation for the systemic prevention and treatment of radiation enteritis. Animal experiments have confirmed that this formulation can significantly alleviate clinical symptoms such as weight loss, diarrhea with bloody stools, increased disease activity index, and shortened colon in radiation enteritis model mice, and improve pathological damage such as colonic mucosal crypt destruction and massive infiltration of inflammatory cells. It can also inhibit excessive intestinal inflammatory response by downregulating the expression of pro-inflammatory factors TNF-α, IL-1β, and IL-6 and upregulating the level of anti-inflammatory factor IL-10, thus making up for the shortcomings of existing clinical symptomatic treatment drugs. The solubilization system of this invention can achieve a drug loading of 10-30 mg / mL for birch bark extract, and the dosage can be flexibly adjusted according to clinical administration needs. After oral administration, it can form a uniform and stable dispersion system in the gastrointestinal tract, improve the local concentration and bioavailability of active ingredients at the intestinal lesion site, ensure stable reproducibility of efficacy, and solve the problems of low drug loading and large fluctuations in efficacy when birch bark extract is directly administered. Attached Figure Description

[0022] Figure 1 This is a flowchart illustrating the preparation process of the birch bark extract solubilizing formulation in Example 1 of the present invention. Figure 2 Appearance images of birch bark extract samples prepared for different solubilization systems, among which Figure 2 A is the poloxamer F68 solubilizing formulation prepared in Example 2. Figure 2 B is the CMC-Na / Tween-80 composite system sample prepared in Comparative Example 1. Figure 2 C is the ethanol system sample prepared in Comparative Example 2. Figure 2 D is the DMSO system sample prepared in Comparative Example 3; Figure 3 This is a graph showing the effects of the birch bark extract solubilized formulation of the present invention on body weight, disease activity index (DAI), and colon length in mice with radiation enteritis. Figure 3 A represents the curve showing the change in mouse body weight. Figure 3 B represents the curve showing the change in the mouse's DAI score. Figure 3 C is an image of the mouse colon. Figure 3 D is a histogram showing the statistical length of the mouse colon; Figure 4 This is a graph showing the effect of the birch bark extract solubilization formulation of the present invention on the expression levels of inflammatory factors in the colonic tissue of mice with radiation enteritis. Figure 4 A represents the TNF-α expression level. Figure 4 B represents the IL-1β expression level. Figure 4 C represents the IL-6 expression level. Figure 4 D represents the IL-10 expression level; Figure 5 HE-stained pathological sections of colon tissue from each group of mice are shown. Figure 5 A represents the normal control group. Figure 5 B is the model group. Figure 5 C represents the positive drug control group. Figure 5 D represents the low-dose birch bark extract group. Figure 5 E represents the medium-dose group of birch bark extract. Figure 5 F represents the high-dose birch bark extract group. Detailed Implementation

[0023] The present invention will be further described below with reference to embodiments.

[0024] The following embodiments are used to illustrate the present invention. Those skilled in the art should understand that the following embodiments are only used to explain the principles and preferred embodiments of the present invention, and are not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

[0025] Unless otherwise specified, the raw materials and reagents used in the embodiments of the present invention are all commercially available pharmaceutical grade or analytical grade products, and the experimental methods used are all conventional pharmaceutical processes and pharmacological experimental methods in the art.

[0026] Example 1: Preparation of a low-dose solubilizing formulation of birch bark extract (see Example 2) Figure 1 ) 1. Raw material formula: 100mg birch bark extract, 1.5g poloxamer F68, 10mL anhydrous ethanol, 10mL purified water.

[0027] The birch bark extract used in this application can be prepared by the method described in the applicant's separate Chinese invention patent application, "Comprehensive Evaluation Method of Birch Bark Quality Based on Fingerprint Spectroscopy Combined with Chemometrics and One Test Multiple Evaluation Method", application number CN202510647512.5, application date May 20, 2025.

[0028] The birch bark extract is derived from white birch ( Betula platyphylla The bark extract of *Suk.*, preferably composed mainly of triterpenoids, has a betulinool content of approximately 46% as determined by HPLC. This extract is highly lipid-soluble and poorly water-soluble, and requires solubilization treatment as described in this application before use in the prevention and treatment of radiation enteritis.

[0029] 2. Preparation steps: S1 Weighing: Accurately weigh the birch bark extract and poloxamer F68 according to the above formula, and set aside; S2 Co-dissolving ultrasound: Add poloxamer F68 to anhydrous ethanol and sonicate for 5 minutes until completely dissolved. Then add birch bark extract and mix well. Continue sonicating for 10 minutes to obtain a homogeneous and transparent mixture. S3 Rotary evaporation to remove alcohol: The above mixture was placed at 40°C for rotary evaporation to completely remove anhydrous ethanol, yielding a solid dispersion of birch bark extract and poloxamer F68. S4 Reconstitution with water: Add 10 mL of purified water to the above solid dispersion and shake until completely dissolved to obtain a low-dose solubilized preparation of birch bark extract, wherein the concentration of birch bark extract is 10 mg / mL.

[0030] 3. Formulation quality: The obtained formulation is a homogeneous, transparent, pale yellow liquid with no visible precipitate. After being stored at room temperature in the dark for 72 hours, it showed no stratification or precipitation, meeting the requirements for drug administration.

[0031] Example 2: Preparation of a solubilizing formulation of birch bark extract using poloxamer F68 (see Example 2) Figure 2 A) Weigh 1.5 g of poloxamer F68 and add it to 10 mL of anhydrous ethanol. Dissolve the mixture by sonication. Add 200 mg of birch bark extract and continue sonication to form a homogeneous mixture. Remove the ethanol by rotary evaporation at 40 °C. Add 10 mL of purified water to redissolve the mixture to obtain a medium-dose solubilized formulation of birch bark extract.

[0032] The resulting formulation was a homogeneous liquid. No obvious precipitation or stratification was observed after 72 hours of storage at room temperature in the dark, indicating that the formulation has good physical stability and can meet the requirements for administration in animal experiments.

[0033] Comparative Example 1: Solubilization Attempt on the CMC-Na / Tween-80 Compound System (see...) Figure 2 B) To examine the applicability of different solubilization systems to birch bark extract, a CMC-Na / Tween-80 compound system was used for comparison.

[0034] Sodium carboxymethyl cellulose was dissolved in hot water, cooled, and then mixed with Tween-80 aqueous solution. Birch bark extract stock solution was then added, and the state of the system was observed.

[0035] The results showed that although the system could form a translucent liquid, a precipitate appeared at the bottom after standing, indicating that the compound system had limited solubilizing ability for birch bark extract and poor system stability.

[0036] Comparative Example 2: Solubilization Attempts on the Ethanol System (see...) Figure 2 C) Weigh 10 mg of birch bark extract and add it to 1 mL of anhydrous ethanol. After sonication, observe its dissolution state.

[0037] The results showed that birch bark extract can form a clear solution in ethanol, but due to the high volatility of ethanol and the fact that this system is not suitable for directly constructing stable aqueous drug delivery formulations, it is not suitable as a final drug delivery system.

[0038] Comparative Example 3: Solubilization test of DMSO system (see...) Figure 2 D) Weigh 10 mg of birch bark extract and add it to 300 μL of DMSO. After vortexing and sonication, observe its dissolution state.

[0039] The results showed that birch bark extract could dissolve briefly in DMSO initially, but a yellowish-white flocculent precipitate easily formed after cooling, indicating that the system was not stable enough to meet the needs of subsequent actual drug administration.

[0040] Example 3: Establishment of an animal model of radiation enteritis and drug administration grouping S1. Experimental animals: SPF-grade male C57BL / 6J mice, 6-8 weeks old, weighing 20±2 g, were selected.

[0041] S2. Model Establishment: A radiation enteritis model was established using local abdominal irradiation. Mice were anesthetized and fixed in a supine position, with their heads, chests, and limbs covered by lead plates, exposing only the abdomen. A single 12 Gy local abdominal irradiation was performed using an X-ray biological irradiator. The irradiation conditions were: 320 kV, 10.8 mA, target-skin distance 50 cm, and dose rate 3 Gy / min. The sham irradiation group underwent the same procedures as the irradiation group, except that the radiation was not turned on.

[0042] S3. Grouping and Dosing The experimental animals were randomly divided into 6 groups of 8 animals each: (1) Normal control group; (2) Model group; (3) Positive drug control group; (4) Low-dose group of birch bark extract; (5) Medium-dose group of birch bark extract; (6) High-dose group of birch bark extract.

[0043] The positive control group was given L-glutamine solution; the low, medium and high dose groups were given birch bark extract solubilization preparations prepared in Examples 1, 2 and 3, respectively.

[0044] The medication was administered by gavage starting one day before irradiation, twice daily for seven consecutive days. The normal control group and the model group received an equal volume of poloxamer F68 solution; the positive control group received L-glutamine solution; and the low, medium, and high dose groups received solubilizing agents containing birch bark extract at 100 mg / kg, 200 mg / kg, and 300 mg / kg, respectively.

[0045] Example 4: Effects of the solubilizing formulation of the present invention on general condition and disease activity index (see Example 4) Figure 3 A and Figure 3 B) During the administration period, the general condition of mice in each group was observed daily, and changes in body weight, fecal characteristics and blood in stool were recorded. Scores were made according to the Disease Activity Index (DAI) scoring criteria.

[0046] The results showed that, compared with the normal control group, the model group mice had significantly lower body weight and significantly higher DAI scores, indicating that the radiation enteritis model was successfully established. Compared with the model group, after administration of the birch bark extract solubilizing agent of this invention, the decrease in body weight and the reduction in DAI scores in mice of all dosage groups were smaller, with more significant improvements in the medium and high dosage groups, indicating that the solubilizing agent of this invention can alleviate the general condition damage caused by radiation enteritis.

[0047] Example 5: Effect of the solubilizing formulation of the present invention on the appearance and length of the colon (see Example 5) Figure 3 C) Mice in each group were sacrificed after the last administration, the colon was completely separated, and removed from the end of the cecum to the anus for external observation and measurement of colon length.

[0048] The results showed that the colon in the model group was significantly shortened, accompanied by pathological changes such as congestion and edema. Compared with the model group, all dosage groups of the birch bark extract solubilization preparation of this invention could improve colonic shortening and appearance damage to varying degrees, with the high-dose group showing the most significant improvement, approaching that of the normal control group. These results indicate that the solubilization preparation of this invention has an ameliorative effect on colonic damage caused by radiation enteritis.

[0049] Example 6: Effect of the solubilizing agent of the present invention on the expression of inflammatory factors (see Example 6) Figure 4 ) Colon tissue from each group of mice was homogenized, and IL-1 was detected using ELISA. β IL-6, TNF-α α and the expression level of IL-10.

[0050] The results showed that, compared with the normal control group, the model group had higher levels of IL-1 in its colon tissue. β IL-6 and TNF-α α The expression levels of pro-inflammatory factors were significantly increased, while the expression level of IL-10 was decreased. Compared with the model group, after intervention with the birch bark extract solubilizing preparation of this invention, IL-1 expression was significantly reduced. β IL-6 and TNF-α α The expression levels of all drugs showed a decreasing trend, while the expression level of IL-10 showed an increasing trend, with more significant improvements observed in the medium and high dose groups. These results indicate that the solubilizing formulation of this invention can regulate the imbalance in the expression of inflammatory factors, thereby alleviating the inflammatory response of radiation enteritis.

[0051] Example 7: Effects of the solubilizing agent of the present invention on pathological damage to colon tissue. After fixation, embedding, and sectioning, the colon tissues of each group were stained with hematoxylin and eosin (HE) and observed under a microscope to examine the structure of the colonic mucosa, the arrangement of crypts, and the infiltration of inflammatory cells.

[0052] The results showed that the colonic tissue structure of the normal control group was intact, and the crypts were arranged regularly; the model group showed obvious crypt destruction, thinning of the mucosal layer, and extensive infiltration of inflammatory cells. Compared with the model group, all dose groups of the birch bark extract solubilization preparation of this invention showed different degrees of pathological improvement, with the high-dose group showing more significant recovery of mucosal structure and a significant reduction in inflammatory cell infiltration. The above results indicate that the solubilization preparation of this invention can effectively alleviate the histopathological damage caused by radiation enteritis.

[0053] Example 9: Summary of Application Effects The results of the above embodiments show that the birch bark extract solubilizing formulation constructed by poloxamer F68 in this invention can significantly improve the solubility, dispersibility and system stability of birch bark extract, and exhibits a clear preventive and therapeutic effect in an animal model of radiation enteritis.

[0054] Specifically, it can alleviate weight loss, diarrhea, bloody stools, elevated DAI scores, colonic shortening, and pathological damage to colonic tissue, while reducing the expression of pro-inflammatory factors and increasing the expression of anti-inflammatory factors. Therefore, the solubilizing formulation described in this invention can be used to prepare drugs for the prevention and treatment of radiation enteritis.

[0055] Further explanation In other embodiments of the present invention, the ratio of birch bark extract to poloxamer F68, the ultrasonic treatment time, the rotary evaporation conditions, and the reconstitution volume can be adjusted appropriately according to actual needs; as long as the obtained preparation can achieve stable solubilization of birch bark extract and has the effect of preventing and treating radiation enteritis, it should be considered to fall within the protection scope of the present invention.

Claims

1. A birch bark extract solubilizing preparation for the prevention and treatment of radiation enteritis, comprising birch bark extract, ethanol, and water, characterized in that, The solubilizing agent uses poloxamer F68 as a solubilizing carrier, and the mass ratio of the birch bark extract to poloxamer F68 is 1:(5-15). The solubilizing agent is prepared by the steps of ethanol co-dissolving, ultrasonic treatment, rotary evaporation to remove alcohol, and water redissolving.

2. The birch bark extract solubilizing preparation for the prevention and treatment of radiation enteritis according to claim 1, characterized in that, The formulation showed no visible precipitation or stratification when placed at room temperature in the dark for 72 hours, and no obvious precipitation of active ingredients.

3. The birch bark extract solubilizing preparation for the prevention and treatment of radiation enteritis according to claim 1, characterized in that, The mass concentration of birch bark extract in the preparation is 10–30 mg / mL.

4. A birch bark extract solubilizing preparation for the prevention and treatment of radiation enteritis according to claim 1, characterized in that, The rotary evaporation process is carried out at a temperature of 35–45°C.

5. A birch bark extract solubilizing preparation for the prevention and treatment of radiation enteritis according to claim 1, characterized in that, The solubilizing agent is an oral liquid formulation.

6. A method for preparing a birch bark extract solubilizing agent for the prevention and treatment of radiation enteritis, characterized in that, The birch bark extract solubilizing formulation for the prevention and treatment of radiation enteritis as described in any one of claims 1 to 5 further comprises the following steps: S1 Weigh out birch bark extract and poloxamer F68 according to the preset mass ratio; S2. Poloxamer F68 was added to ethanol and sonicated until completely dissolved. Then, birch bark extract was added and mixed evenly. The mixture was sonicated again to obtain a homogeneous and transparent mixture. S3 The homogeneous mixture obtained in step S2 is subjected to rotary evaporation at 35-45°C to completely remove ethanol, resulting in a solid dispersion of birch bark extract and poloxamer F68. S4. Add purified water to the solid dispersion obtained in step S3, and stir or shake until completely dissolved to obtain a homogeneous and stable birch bark extract solubilization preparation.

7. The method for preparing a birch bark extract solubilizing agent for the prevention and treatment of radiation enteritis according to claim 6, characterized in that, The ethanol mentioned in step S2 is anhydrous ethanol.

8. A method for preparing a birch bark extract solubilizing agent for the prevention and treatment of radiation enteritis according to claim 6, characterized in that, The total duration of the ultrasonic treatment in step S2 is 5 to 30 minutes.

9. The application of a birch bark extract solubilizing agent in the preparation of drugs for preventing and treating radiation enteritis, characterized in that, It is applied to the birch bark extract solubilization formulation for the prevention and treatment of radiation enteritis as described in any one of claims 1 to 5.

10. The application of the birch bark extract solubilizing preparation according to claim 9 in the preparation of drugs for preventing and treating radiation enteritis, characterized in that, The drug is used to achieve at least one of the following effects: (1) Reduce weight loss, diarrhea, hematochezia, shortening of the colon and pathological damage to colon tissue caused by radiation enteritis; (2) Reduce the pro-inflammatory factor TNF-α α IL-1 β It reduces the expression level of at least one of IL-6 and increases the expression level of the anti-inflammatory factor IL-10.

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