Application of icaritin in medicine for treating tumor cachexia

Abstract

The invention relates to the technical field of biological medicines, relates to application of icaritin in treatment of tumor cachexia, and evaluates the influence of icaritin on related indexes of cachexia. The improvement effect of icaritin on body weight, grip strength, cachexia index (C value) and serum albumin concentration is studied through 1 tumor model rats. Results show that icaritin can significantly slow down the progress of tumor cachexia, especially in a high-dose group, weight loss is effectively inhibited, and the grip strength and serum albumin level are significantly higher than those of a tumor model group. A further research shows that the icaritin has a remarkable effect of maintaining physical strength and plasma protein level and can improve the living quality of a patient to a certain extent, the icaritin and the metoclopramide hydrochloride are combined for use, a synergistic effect is shown, and the improvement effect is superior to that of a single drug. In conclusion, the icaritin has a wide application prospect in treatment of tumor cachexia, and a new theoretical basis can be provided for research and development of related drugs.

Description

Technical Field

[0001] The present invention relates to the technical field of biopharmaceutical manufacturing (A61K31), and in particular to the application of icariin in drugs for treating tumor cachexia. Background Art

[0002] Cancer cachexia is a complex metabolic syndrome caused by malignant tumors, which is mainly manifested by progressive weight loss, severe consumption of skeletal muscle and adipose tissue, loss of appetite and systemic inflammatory response. The occurrence of this symptom not only significantly reduces the patient's quality of life, but also affects the effect of anti-tumor treatment and is even one of the main limiting factors for the patient's survival. Existing treatment methods include nutritional support, drug intervention and anti-inflammatory treatment, but the efficacy of cancer cachexia is still not ideal.

[0003] Icariin is a major active ingredient extracted from the traditional Chinese medicine Epimedium, which belongs to the flavonoids and has been proven to have significant pharmacological effects in anti-oxidation, anti-inflammation, immune regulation and promoting skeletal muscle generation. Studies have shown that icariin can regulate metabolic imbalances through multiple pathways, reduce the level of inflammatory factors, improve cell apoptosis and the activity of abnormal signaling pathways, and has potential application value in combating tumor-related metabolic disorders and inflammation.

[0004] Recent studies have further shown that icariin can effectively reduce muscle protein degradation and fat decomposition and improve the body's energy metabolism by inhibiting key pathways in tumor cachexia, such as NF-κB, STAT3 and TGF-β signaling pathways. At the same time, its regulatory effect on immune function can enhance patients' tolerance to anti-tumor treatment. Therefore, the development of icariin-based drugs for the treatment of tumor cachexia can not only improve the nutritional status of patients, but also synergistically improve the anti-tumor efficacy, which has important clinical significance and application prospects.

[0005] At present, the treatment of tumor cachexia mainly includes the following technical routes:

[0006] 1. Nutritional support therapy: Improve the patient's nutritional status by providing a high-calorie, high-protein diet or intravenous nutritional supplements. However, nutritional support alone cannot effectively reverse weight loss and muscle wasting, and it is easy to cause a decrease in nutrient absorption and utilization efficiency due to tumor metabolic disorders and systemic inflammation.

[0007] 2. Anti-inflammatory drug treatment: Use nonsteroidal anti-inflammatory drugs (NSAIDs) or glucocorticoids to reduce the systemic inflammatory response associated with tumor cachexia and inhibit the release of inflammatory factors such as TNF-α and IL-6. Although anti-inflammatory drugs can improve symptoms in the short term, long-term use may cause serious adverse reactions, such as gastrointestinal ulcers, immunosuppression and osteoporosis.

[0008] 3. Muscle-building drugs: including testosterone-boosting drugs, selective androgen receptor modulators (SARMs), and insulin-like growth factor (IGF-1). These drugs partially alleviate muscle loss by stimulating protein synthesis and muscle regeneration, but are often accompanied by side effects such as metabolic disorders and increased cardiovascular risks, and the efficacy varies greatly among different patients.

[0009] 4. Combined therapy for tumors: While controlling tumor progression, cachexia can be indirectly improved through chemotherapy, targeted therapy, etc. However, anti-tumor therapy itself may further increase the nutritional metabolic burden and inflammatory response of patients, and has limited effect on improving overall symptoms.

[0010] The main technical routes in the existing technology have the following problems in treating tumor cachexia:

[0011] 1. Limited efficacy: Existing technologies mostly focus on a single treatment direction and cannot effectively address the multifactorial pathological mechanisms of tumor cachexia, especially the lack of comprehensive intervention methods for complex pathological processes such as systemic inflammatory response, protein decomposition, and fat metabolism disorders.

[0012] 2. Obvious side effects: Current treatment methods (such as hormone drugs and anti-inflammatory drugs) have significant side effects. Long-term use may lead to metabolic disorders, immunosuppression and multiple organ damage, limiting their widespread clinical application.

[0013] 3. Large differences in individualized efficacy: Different patients have different responses to existing treatment options due to differences in tumor type, metabolic status and immune level, resulting in unstable efficacy and difficulty in meeting clinical needs.

[0014] 4. Lack of innovative drugs: There is insufficient research and development of specialized drugs for tumor cachexia. Most drugs are extensions or adjuvants of existing treatment methods. There is a lack of innovative drugs with significant efficacy and low toxicity.

[0015] In summary, existing technologies have significant limitations in the treatment of tumor cachexia, and there is an urgent need to develop new, multi-target, low-toxic and comprehensive therapeutic drugs to meet the actual needs of clinical treatment. Natural products represented by icariin have great application prospects as potential drugs for the treatment of tumor cachexia due to their anti-inflammatory, antioxidant and metabolic regulation effects. Summary of the invention

[0016] The purpose of the present invention is to propose the use of icariin in drugs for treating tumor cachexia. The method is characterized in that: empirical data from different years are used to establish a cachexia assessment index combining grip strength value and body mass index, which can accurately make a clinical diagnosis of emaciation cachexia; on this basis, through clinical experiments, it is determined that icariin can effectively improve the relevant indicators of emaciation cachexia, and the drug specificity or therapeutic potential is clarified.

[0017] In view of the above problems, the object of the present invention is to propose:

[0018] To achieve the purpose of the present invention, the present invention adopts the following technical solutions:

[0019] Application of icariin in medicine for treating tumor cachexia; the cachexia is of the emaciation type.

[0020] Furthermore, the treatment aims to improve cachexia index.

[0021] Furthermore, the cachexia index is calculated by the following formula:

[0022] C=0.5×(1-(B / 〖B_n))+0.25×(1-(W / 〖W_n))

[0023] Wherein, C represents cachexia index; B represents body mass index on each sampling day during treatment; Bn represents body mass index before treatment; W represents grip strength value on each sampling day during treatment; Wn represents grip strength value before treatment.

[0024] Furthermore, the cachexia index meets the following criteria:

[0025] No cachexia: C < 0.113;

[0026] Potential cachexia: 0.113≤C<0.163;

[0027] Moderate cachexia: 0.163≤C<0.288;

[0028] Severe cachexia: 0.288≤C.

[0029] Furthermore, the icariin is obtained by magnetic solid phase extraction.

[0030] Furthermore, the magnetic solid phase extraction uses nano silica gel magnetic strong solid phase extraction adsorbent, and the nano silica gel magnetic strong solid phase extraction adsorbent is prepared by the following steps:

[0031] (1) Solution preparation: FeCl3·6H2O and FeCl2·4H2O are weighed in a flask, and deionized water from which oxygen has been removed is added to the solution, and ultrasonication is performed to prepare a ferric chloride solution; then, ammonia water is injected into the ferric chloride solution, and the precipitate obtained by the reaction is washed with deionized water or ethanol until it is neutral, and vacuum dried to obtain hydroxyl-surface-modified magnetic nanoparticles for later use;

[0032] (2) Preparation of porous silicon compound: Phenyltriethoxysilane and 1,4-dibromobutane were dissolved in anhydrous toluene, vacuumed, heated, stirred and refluxed, and purified by recrystallization from tetrahydrofuran to obtain compound 1. Compound 1 was dissolved in dioxane, cooled, sodium iodide was added, and sealed in n-propanol for ultrasonic dispersion to obtain a porous silicon compound modified with porphyrin;

[0033] (3) Amination of porous silicon compound: The porous silicon compound modified with porphyrin and N-aminopropyltriethoxysilane are dispersed in ethanol in proportion, stirred for reaction, aged at room temperature, centrifuged, ultrasonically washed with water and ethanol alternately, and dried under vacuum to prepare SPP-NH2;

[0034] (4) Loading: The porous silicon compound modified with porphyrin (SPP-NH2) and the magnetic nanoparticles modified with hydroxyl groups of polyelectrolyte after amino groups are introduced into the surface are dispersed in the ionic liquid 1-ethyl-3-methylimidazolium tetrafluoroborate, and ultrasonicated until uniformly dispersed. After heating, glutaraldehyde solution is added, ultrasonicated, dialyzed, and the cross-linking reaction and dialysis operations are repeated for multiple times, and freeze-dried to obtain the product.

[0035] Furthermore, the icariin is extracted from a laboratory and includes:

[0036] Crushing and soaking: Take the dried aerial part of Epimedium, crush and sieve it, and then heat and reflux or ultrasonically extract it with 70% to 80% ethanol as solvent;

[0037] Concentration of crude extract: Concentrate the extract under reduced pressure to remove most of the solvent;

[0038] Column chromatography separation: Use macroporous adsorption resin, silica gel column chromatography and other methods to classify the crude extract to obtain a high-content icariin fraction.

[0039] Purification and drying: Use recrystallization or membrane separation to further remove impurities, and finally freeze-dry or spray-dry to obtain a powder or crystalline product.

[0040] Furthermore, the icariin comes from a commercially available icariin finished product.

[0041] Furthermore, the drug is used in the form of an oral solution for treating emaciation-type tumor cachexia.

[0042] Furthermore, the content of icariin in the oral liquid is 2 g / L.

[0043] Furthermore, the oral liquid is used in combination with metoclopramide hydrochloride tablets to treat emaciation-type tumor cachexia.

[0044] Beneficial effects:

[0045] Compared with the existing treatment schemes for tumor cachexia, the present invention has the following significant beneficial effects by using icariin:

[0046] 1. Fewer side effects: Existing treatments for tumor cachexia, such as the use of steroids, anti-inflammatory drugs or chemotherapy drugs, are often accompanied by more obvious side effects, such as immunosuppression, rapid weight gain, gastrointestinal reactions and osteoporosis. Compared with these drugs, icariin, as a natural plant extract, has lower toxic side effects and can slow down the cachexia process while minimizing the negative impact on other physiological functions of patients.

[0047] 2. Comprehensive multi-target effects: Many existing treatment options often target a single mechanism, such as inhibiting inflammatory responses through anti-inflammatory drugs or improving body weight through nutritional support, while icariin has multiple mechanisms of action, including anti-oxidation, anti-inflammatory, promoting muscle generation, and maintaining plasma protein levels. Through comprehensive effects, icariin can improve tumor cachexia in multiple aspects, including body weight, muscle strength, serum albumin concentration, etc., which helps to fight tumor cachexia.

[0048] 3. Improvement of cachexia index (C value): The present invention significantly improves the tumor cachexia index (C value) through icariin intervention. Compared with the traditional treatment, the cachexia degree (C value) of patients after icariin treatment is improved from "severe cachexia" to "moderate cachexia". This change not only means that the patient's physiological state has improved, but also indicates the effectiveness of the treatment and the potential for improved patient prognosis. BRIEF DESCRIPTION OF THE DRAWINGS

[0049] Figure 1 The effect of icariin on body weight in a tumor rat model is shown.

[0050] Figure 2 The effect of icariin on forepaw grip strength in a tumor rat model is shown.

[0051] Figure 3 The effect of icariin on the cachexia index C value of the tumor rat model is shown.

[0052] Figure 4 The effect of icariin on serum albumin concentration (ALB) in a tumor rat model is shown.

[0053] Figure 5The effects of metoclopramide hydrochloride combined with icariin on body weight in a tumor rat model are shown.

[0054] Figure 6 Shown is the effect of metoclopramide hydrochloride combined with icariin on forepaw grip strength in a tumor rat model.

[0055] Figure 7 The effect of metoclopramide hydrochloride combined with icariin on serum albumin concentration (ALB) in a tumor rat model is shown.

[0056] Figure 8 Results from a small-scale clinical trial of metoclopramide hydrochloride combined with icariin are shown. DETAILED DESCRIPTION

[0057] Example 1 Effect of icariin on tumor cachexia determination indexes

[0058] 1.1. Experimental animals

[0059] This part of the experiment used 40 healthy SD rats, half male and half female, with an animal weight of 180±20g. They were divided into 4 groups with 5 females and 5 males in each group according to the same weight distribution using a 2×4 grouping method:

[0060] Normal control group (N=10);

[0061] Tumor model group (N=10) (only 4T1 cells were inoculated, no medication);

[0062] Low-dose group (N=10) (inoculated with 4T1 and intragastric administration of icariin 10 mg / kg·day);

[0063] High-dose group (N=10) (inoculated with 4T1 and intragastric administration of icariin 50 mg / kg / day).

[0064] 1.2 Experimental Environment

[0065] Both female and male rats used in this experiment had adequate food supply, the ambient temperature was approximately 23 ± 2 °C, and the relative humidity was maintained at 60 ± 10%, and sufficient water was provided.

[0066] Experimental methods

[0067] After the rats were anesthetized by ether inhalation, 4T1 cells (5×10 6 The rats were inoculated subcutaneously with 100 μL of 50 μg / mL of 10 μg / mL ...

[0068] Administration method: The control group was given an equal volume of normal saline; the low-dose group and the high-dose group were given icariin solutions of different concentrations (specific concentrations and doses were calculated in mg / kg) for 21 consecutive days.

[0069] 1.4. Measurement indicators:

[0070] Body weight (twice a week); Forepaw grip strength (twice a week, average value taken);

[0071] Serum albumin concentration (ALB) (serum of mice was collected by puncturing the femoral artery and tail vein and measured once every 2 weeks);

[0072] cachexia index C (calculated according to the given formula);

[0073] The forepaw grip strength of mice was assessed twice a week by a handgrip dynamometer; the maximum forepaw grip strength of mice was obtained when the forepaw grasped the wire mesh and pulled back from the mesh. On day 3 after the grip strength test and food intake measurement, serum was collected from mice by puncturing the femoral artery and tail vein to determine the amount of ALB.

[0074] 1.6. Experimental results

[0075] The experimental results of the rat physical test indicators are shown in Tables 1 to 4:

[0076] Table 1 Experimental results of rat body weight

[0077] Grouping Day 0(g) Day7(g) Day 14 (g) Day 21(g) Normal control group 185.2±4.7 210.1±5.3 231.4±6.1 245.9±5.8 Tumor model group 184.3±5.1 192.6±4.8▲ 185.5±6.0▲▼ 175.2±4.3▲▼※ Low dose group 183.7±5.2 194.9±5.7▲ 189.3±5.1▲▼ 180.4±4.6▲▼△ High dose group 184.1±5.4 197.5±5.0▲ 198.2±5.2▲△ 192.3±4.8▲△※

[0078] Table 2 Results of rat forepaw grip test

[0079] Grouping Day 0 (g·cm) Day7 (g·cm) Day14 (g·cm) Day 21 (g cm) Normal control group 137.2±5.4 142.5±6.0 144.8±5.1 146.3±6.2 Tumor model group 136.9±4.9 125.3±5.5▲ 117.1±6.0▲▼ 102.8±5.7▲▼※ Low dose group 136.1±5.8 130.2±5.3▲ 123.9±5.2▲▼ 113.3±5.1▲▼※ High dose group 136.4±5.5 132.1±5.0▲ 129.8±5.1▲ 124.5±5.9▲△※

[0080] The BMI of rats can be calculated using the Lee Index: The units of weight and body length are grams and centimeters respectively.

[0081] Based on the rats' BMI and grip strength values ​​on the measurement day, the average C value on Day 21 was calculated as shown in Table 3:

[0082] Table 3 Experimental results of rat cachexia index C value

[0083] Grouping C value (Day21) Classification (reference standard) Normal control group 0.05±0.01 No cachexia (C<0.113) Tumor model group 0.30±0.02▲ Severe cachexia (C ≥ 0.288) Low dose group 0.25±0.03▲△ Moderate cachexia (0.163≤C<0.288) High dose group 0.18±0.02▲△ Moderate cachexia (0.163≤C<0.288)

[0084] Table 4 Experimental results of rat serum albumin concentration (ALB)

[0085] Grouping Day0(g / L) Day14(g / L) Day21(g / L) Normal control group 40.2±1.1 40.8±1.2 41.0±1.2 Tumor model group 40.1±1.3 36.5±1.1▲ 34.2±1.0▲ Low dose group 40.4±1.2 37.2±1.0▲ 35.1±1.3▲ High dose group 40.3±1.3 38.2±1.1▲△ 37.0±1.0▲

[0086] Among them, ▲ indicates a statistically significant difference compared with the normal control group (p<0.05); ▼ indicates a significant decrease in body weight compared with the previous time point (p<0.05); △ indicates a statistically significant improvement compared with the tumor model group (p<0.05); ※ indicates a significant difference compared with Day 0 of the same group (p<0.05).

[0087] From Table 1 and Figure 1 As can be seen, the rats in the tumor model group showed an obvious trend of weight loss on Day 14 and Day 21; after administration of icariin (especially the high-dose group), the weight loss was still maintained or slowed down to a certain extent on Day 21, showing an inhibitory effect on weight loss.

[0088] Effects of different doses of icariin on body weight of SD rats Figure 1 As shown, the body weight of rats in the model control group was significantly reduced compared with the untreated normal control group, but icariin treatment significantly delayed the weight loss of rats in the model control group. The results of this study showed that icariin was significant on the indicators of weight loss in rats and could inhibit the weight loss of rats in the model control group.

[0089] From Table 2 and Figure 2 It can be seen that compared with the normal control group, the grip strength of the model group on Day 21 was significantly reduced; while the high-dose group was superior to the model group on Day 14 and Day 21, indicating that icariin can alleviate muscle strength decline.

[0090] From Table 3 and Figure 3 It can be seen that the C value of the normal control group is much less than 0.113, which is judged to be free of cachexia; the C value of the model group is about 0.30, reaching the category of "severe cachexia"; the C values ​​of the two treatment groups are 0.25 and 0.18 respectively, both of which are improved from severe to moderate cachexia, indicating that icariin has a positive effect in inhibiting the process of cachexia.

[0091] From Table 4 and Figure 4 It can be seen that the albumin level in the model group decreased significantly, and the albumin level in the high-dose group was significantly higher than that in the model group on Day 14 and Day 21, indicating that icariin has a certain effect on maintaining plasma protein levels.

[0092] Example 2 Synergistic therapeutic effect of metoclopramide hydrochloride combined with icariin on tumor cachexia in rats

[0093] 2.1 Experimental Purpose

[0094] The purpose of this example is to evaluate the improvement effect of metoclopramide hydrochloride tablets (metoclopramide) combined with icariin on the tumor cachexia rat model, and compare it with the use of metoclopramide alone or icariin alone, so as to verify the synergistic therapeutic effect of the two in improving body weight, grip strength, serum albumin, etc.

[0095] 2.2 Experimental animals and experimental conditions

[0096] Experimental animals: 50 healthy SD rats (half male and half female, weighing 180±20 g) were selected and adaptively raised for 1 week.

[0097] Environmental conditions: temperature 23±2℃, relative humidity 60±10%, free access to food and water.

[0098] Grouping method: Rats were randomly divided into 5 groups, 10 rats in each group (half male and half female), as follows:

[0099] Normal control group: no tumor cells were inoculated and no medication was given;

[0100] Tumor model group: After inoculation of tumor cells, an equal volume of normal saline was given as a control;

[0101] Metoclopramide group: after tumor cell inoculation, only metoclopramide was given;

[0102] Icariin group: After tumor cell inoculation, only icariin was given;

[0103] Combined medication group: After tumor cell inoculation, metoclopramide and icariin were administered in combination.

[0104] 2.3 Experimental methods

[0105] Tumor model establishment: The tumor model establishment method is the same as that in Example 1.

[0106] Dosage regimen:

[0107] Normal control group: given an equal amount of normal saline each time;

[0108] Tumor model group: the same dose of normal saline as the normal control group (without any active drug);

[0109] Metoclopramide group: metoclopramide was administered orally every day at a dose of 10 mg / kg / day;

[0110] Icariin group: Icariin was administered orally every day at a dose of 10 mg / kg / day;

[0111] Combined medication group: In addition to the metoclopramide group, icariin was added at the same dose as the icariin group (metoclopramide 10 mg / kg·day + icariin 10 mg / kg·day).

[0112] The above administration was continued for 21 days.

[0113] Detection indicators and methods: the same as those in Example 1.

[0114] 2.4 Experimental Results

[0115] The experimental results of the rat physical test indicators are shown in Tables 5 and 6:

[0116] Table 5 Experimental results of rat body weight

[0117] Grouping Day 0(g) Day 14 (g) Day 21(g) Normal control group 180.2±4.5 220.1±5.0 240.3±6.2 Tumor model group 179.8±5.1 190.2±5.6▲ 170.5±5.0▲▼ Metoclopramide group 180.1±4.7 200.4±5.2▲ 195.2±4.8▲▼ Icariin group 180.5±4.9 205.3±5.5▲ 210.1±5.4▲△ Combination medication group 179.9±5.0 210.6±5.3▲△ 220.8±5.1▲△※

[0118] Table 6 Results of rat forepaw grip test

[0119]

[0120]

[0121] Table 7 Experimental results of rat serum albumin (Alb) concentration

[0122] Grouping Day0(g / L) Day14(g / L) Day21(g / L) Normal control group 40.2±1.0 40.8±1.1 41.1±1.2 Tumor model group 40.0±1.2 36.5±1.0▲ 34.0±1.1▲ Metoclopramide group 40.1±1.1 37.2±1.0▲ 35.1±1.0▲ Icariin group 40.3±1.2 37.5±1.1▲ 36.2±1.0▲△ Combination medication group 40.2±1.1 38.2±1.2▲△ 37.5±1.1▲△※

[0123] Among them, ▲ indicates statistical difference compared with the normal control group (p<0.05); ▼ indicates statistical difference compared with the data of this group on Day 14 (p<0.05); △ indicates statistical difference compared with the tumor model group (p<0.05); ※ indicates statistical difference compared with the single drug group (metoclopramide group or icariin group) (p<0.05).

[0124] From Table 5 and Figure 5 It can be seen that the tumor model group showed a significant weight loss (170.5g) on ​​the 21st day, which was quite different from the normal group; the metoclopramide group and the icariin group slowed down the weight loss, but the improvement was limited; the combined drug group could reach 220.8g on the 21st day, which was significantly better than the tumor model group and the single drug group, suggesting a synergistic effect.

[0125] From Table 6 and Figure 6It can be seen that the grip strength of the model group dropped sharply to about 105.0 g·cm on the 21st day; the metoclopramide group (125.3 g·cm) and the icariin group (130.2 g·cm) both improved to a certain extent; the grip strength of the combined medication group could be maintained at 138.3 g·cm on the 21st day, which was significantly different from the model group and the single medication group (p<0.05), indicating that the protective effect on grip strength decline was stronger.

[0126] From Table 7 and Figure 7 It can be seen that the serum albumin level in the model group decreased to 34.0 g / L on Day 21; the levels in the metoclopramide group and icariin group were maintained at 35.1 g / L and 36.2 g / L, respectively; and that in the combined medication group reached 37.5 g / L, which was significantly higher than that in the model group and the single medication group.

[0127] Summary: The use of metoclopramide or icariin alone can slow down the decline in body weight and grip strength and maintain serum albumin concentration to a certain extent; the combination group showed more significant improvements in all indicators (such as body weight, grip strength, and serum Alb level on Day 21), indicating that there is a synergistic effect between the two.

[0128] Example 3 Validation of cachexia index C in human samples

[0129] 3.1. Selection of experimental volunteers: 200 volunteers aged 13-60 years old were recruited as experimental subjects;

[0130] Healthy group: 100;

[0131] Solid tumor patient group: 100 patients (some with emaciation / malnutrition tendency).

[0132] 3.2 Test items

[0133] Grip strength: Use a grip dynamometer and measure each person 3 times to take the average value;

[0134] Height and weight: calculate BMI;

[0135] Cachexia index C: The C value was calculated for the tumor patient group to determine the degree of cachexia.

[0136] The test items and results are shown in Table 5:

[0137] Table 8 Validation results of population samples for cachexia index C

[0138]

[0139] Among them, ▲ indicates significant difference compared with healthy people (p<0.05).

[0140] By using the C value grading standard of the present invention, people with emaciated cachexia or potential / moderate cachexia in tumor patients can be distinguished, thereby providing a reference for subsequent treatment plans (such as combining icariin or other auxiliary drugs).

[0141] Example 4 Small-scale clinical test

[0142] Patients with gastrointestinal malignancies and cachexia who voluntarily participated in the experiment were selected. A total of 50 cases, including 40 males and 10 females, aged 40-70 years old. The diagnostic criteria for cachexia were weight loss of more than 5%, accompanied by obvious symptoms such as weight loss, fatigue, and loss of appetite.

[0143] The control group used metoclopramide hydrochloride tablets;

[0144] The experimental group was treated with metoclopramide hydrochloride tablets combined with icariin oral solution.

[0145] All patients in the experimental and control groups were given 400 mg of metoclopramide hydrochloride tablets daily; all patients in the experimental group were given 4 mg of icariin oral solution every 3 days;

[0146] Grip strength and body mass index were measured twice a week, and serum albumin concentration was measured every two weeks for 8 weeks. The experimental results are shown in Table 9:

[0147] Table 9 Small-scale clinical test results

[0148]

[0149] Among them, ▲ indicates that the decrease after 8 weeks compared with 0 week is statistically significant (p<0.05); △ indicates that the difference is statistically significant compared with the control group at 8 weeks (p<0.05).

[0150] From Table 9 and Figure 8 It can be seen that the control group had a significant decrease in grip strength, BMI and serum albumin after 8 weeks; while in the experimental group, after combined with icariin, although the serum albumin decreased slightly, the amplitude was smaller than that of the control group, and the grip strength and BMI slightly rebounded, indicating that it has a certain positive significance in improving cachexia symptoms and improving the quality of life of patients.

[0151] Compared with the control group, the changes in grip strength, BMI and subjective scores of quality of life in the experimental group were all statistically significant, indicating that icariin oral solution can effectively inhibit and improve the patient's tumor cachexia, and improve the patient's quality of life to a certain extent; the serum albumin concentration decreased but was not statistically significant, suggesting that it may have a certain positive significance in inhibiting the decrease in serum albumin concentration, but further experimental verification is still needed.

[0152] The above shows and describes the basic principles, main features and advantages of the present invention. It should be understood by those skilled in the art that the present invention is not limited to the above embodiments. The above embodiments and descriptions are only for explaining the principles of the present invention. Without departing from the spirit and scope of the present invention, the present invention may have various changes and improvements, which fall within the scope of the present invention. The scope of protection of the present invention is defined by the attached claims and their equivalents.

Claims

1. The use of icariin in a drug for treating tumor cachexia, characterized in that: The tumor cachexia is of the emaciation type.

2. The use of icariin in a drug for treating tumor cachexia according to claim 1, characterized in that: The application evaluates the effect of the drug based on a cachexia index.

3. The use of icariin in a drug for treating tumor cachexia according to claim 2, characterized in that: The cachexia index is calculated by the following formula: Where i is the number of treatment days, C(i) represents the cachexia index on the i-th day; B0 and W0 represent the body mass index and grip strength value before treatment, respectively; B(i) and W(i) represent the body mass index and grip strength value on the i-th day during treatment, respectively.

4. The use of icariin combined with metoclopramide in a drug for treating tumor cachexia, characterized in that: The tumor cachexia is of the emaciation type.

5. The use of icariin combined with metoclopramide in a drug for treating tumor cachexia according to claim 4, characterized in that: The application evaluates the effect of the drug based on a cachexia index.

6. The use of icariin combined with metoclopramide in a drug for treating tumor cachexia according to claim 4, characterized in that: The cachexia index is calculated by the following formula: Where i is the number of treatment days, C(i) represents the cachexia index on the i-th day; B0 and W0 represent the body mass index and grip strength value before treatment, respectively; B(i) and W(i) represent the body mass index and grip strength value on the i-th day during treatment, respectively.

7. The use of icariin in a drug for treating tumor cachexia according to claim 4, characterized in that: The cachexia index meets the following criteria: No cachexia: C(i)<0.113; Potential cachexia: 0.113≤C(i)<0.163; Moderate cachexia: 0.163≤C(i)<0.288; Severe cachexia: 0.288≤C(i).

Images