A liposomal curcumin composition for assisting in the management of nodular disease and uses thereof

Abstract

The application discloses a liposome curcumin composition for assisting in regulating nodular diseases and application thereof, and belongs to the technical field of health foods. The composition is composed of 60-80 nm liposome curcumin, 3-10 g / portion of inulin, 10-80 mg / portion of cardamom extract, 100-1000 mg / portion of myo-inositol and 20-100 mu g / portion of selenium element. The liposome is prepared by using food-grade phospholipid, the encapsulation efficiency is greater than or equal to 80%, the ethanol residue is less than or equal to 0.5 ‰, the release rate in a pH 2.0 simulated gastric juice for 2 hours is less than 33%, and the release rate in a pH 7.4 simulated intestinal juice for 4 hours is greater than 80%. The application is based on the theory of treating different diseases in the same way, and four types of nodular core pathogenesis, such as inflammatory accumulation, endocrine disorder, oxidative stress and immune imbalance, are simultaneously intervened by the synergistic effect of multiple components, so that the synchronous auxiliary regulation of thyroid, breast and uterus multiple types of nodules is realized. The product fills the blank of lack of effective intervention means in the clinical regular observation period, and is suitable for the daily regulation of patients with various nodular diseases and the use for preventing recurrence after operation.

Description

Technical Field

[0001] This invention belongs to the field of health food technology, and specifically relates to a liposomal curcumin composition for the adjuvant treatment of nodular diseases and its application. Background Technology

[0002] Thyroid nodules, breast nodules, and uterine fibroids are the three most common types of benign nodular diseases among women of reproductive age and perimenopause. Epidemiological statistics show that the detection rate of thyroid nodules in adult women in my country can reach 38.6%-52.3%, the ultrasound detection rate of breast nodules is 29.8%-43.7%, and the clinical detection rate of uterine fibroids is 20.1%-35.4%. These three diseases often occur together, and the probability of the same patient having two or more types of nodules at the same time is as high as 31.2%. From the perspective of pathogenesis, although the three types of diseases occur in different locations, their core causes are highly consistent: First, chronic inflammation accumulates in the body. Under long-term inflammatory conditions, pro-inflammatory factors such as TNF-α, IL-6, and COX-2 are continuously highly expressed, leading to repeated damage and repair of local tissue cells and inducing abnormal proliferation. Second, endocrine and metabolic disorders occur, with an imbalance in estrogen and progesterone levels. In particular, under estrogen dominance, excessive growth of thyroid follicular epithelial cells, mammary duct epithelial cells, and uterine smooth muscle cells is directly stimulated. Third, oxidative stress damage occurs, with a decrease in the ability to scavenge free radicals. The accumulation of oxidative products leads to cellular DNA damage, which in turn causes abnormal cell proliferation regulation mechanisms. Fourth, immune imbalance occurs, with Th1 / Th2 cytokine drift. The immune cells' ability to recognize and clear abnormally proliferating cells decreases, making it impossible to clear early lesion cells in time, ultimately leading to nodule formation and progression.

[0003] Current clinical intervention strategies for such benign nodular diseases have significant limitations: For asymptomatic nodules with a diameter of less than 1 cm, the clinical approach is generally "regular ultrasound follow-up + observation" without any proactive intervention. This leads to an increased risk of nodule progression during the follow-up period due to the lack of effective management methods. Data shows that approximately 17.3% of patients with thyroid nodules experienced an increase in size during the 12-month follow-up period, while the proportion of breast nodules and uterine fibroids increased by 14.8% and 22.1%, respectively. For larger nodules or those causing compressive symptoms, surgical resection is often used. However, surgery is highly invasive, has a long recovery period, and a high recurrence rate. The 5-year recurrence rate for thyroid nodules is 31.2%, and the recurrence rate for uterine fibroids is as high as 53.6%. In addition, surgery may lead to complications such as hypothyroidism, mammary duct damage, and uterine adhesions, which seriously affect the patient's quality of life.

[0004] Existing commercially available nodule treatment products also have many shortcomings: First, they lack specificity. Most products are designed for only a single type of nodule, failing to meet the simultaneous treatment needs of multiple organs such as the thyroid, breast, and uterus. Patients with multiple nodules need to take multiple products, increasing the burden on their bodies and financial costs. Second, the activity of the active ingredients is insufficient. Taking ordinary curcumin products as an example, curcumin itself has extremely poor water solubility (water solubility <0.1μg / mL) and extremely low oral bioavailability (only 0.01%-1%). After oral administration of conventional preparations, most of it is not absorbed and is excreted in the feces. Even if a small amount is absorbed, it is still difficult to absorb. The drug is rapidly metabolized and inactivated by the liver, failing to reach effective blood concentrations, and exhibits weak anti-inflammatory and antioxidant effects. Third, the formulation is often unreasonable, with some products containing only curcumin without synergistic ingredients, failing to intervene in the nodule development mechanism through multiple pathways. Fourth, outdated manufacturing processes result in tablets and hard capsules being easily destroyed in the acidic environment of the stomach, leading to premature release and loss of active ingredients, and preventing precise delivery to the intestinal absorption site, further reducing bioavailability. Fifth, safety is questionable, with some products illegally adding hormonal components, which may appear effective in the short term, but long-term use can lead to further endocrine disorders and increase the risk of nodule progression.

[0005] To address the aforementioned technical challenges, the industry has attempted various improvement solutions. For example, cyclodextrin inclusion technology was used to improve the water solubility of curcumin, but its encapsulation efficiency was only 40%-60%, and the drug loading was low, making large-scale application impossible. Nanoparticle suspension technology was used to reduce the particle size of curcumin, but the particles had poor stability, were prone to aggregation and precipitation, and caused significant gastrointestinal irritation. Ordinary liposomes were used to encapsulate curcumin, but the particle size was mostly between 100-500 nm, resulting in low transmembrane absorption efficiency and an encapsulation efficiency of less than 70%, making drug leakage easy during storage. Furthermore, the lack of synergistic formulation of components targeting the specific pathological mechanisms of nodular diseases meant that simultaneous and efficient treatment of multiple types of nodules was still not possible.

[0006] Therefore, it is necessary to develop a safe health food with high absorption efficiency, strong targeting, synergistic effects of multiple components, and the ability to simultaneously assist in the treatment of various types of nodules in the thyroid, breast, and uterus. Summary of the Invention

[0007] In view of this, the present invention provides a liposomal curcumin composition for the adjuvant treatment of nodular diseases and its application, in order to solve or alleviate one of the technical problems existing in the prior art, and at least provide a beneficial alternative.

[0008] The technical solution of this invention is implemented as follows: a composition for the adjunctive treatment of nodular diseases, comprising the following raw materials measured per part: Liposome curcumin (60-80nm), inulin 3-10g, cardamom (Elettaria cardamomum) extract 10-80mg, myo-inositol 100-1000mg, selenium 20-100μg; The selenium element is derived from one or more of selenomethionine, sodium selenite, and selenium yeast. The liposome curcumin is prepared using food-grade phospholipids. The phospholipid wall material is selected from one or more of soybean lecithin, sunflower lecithin, and egg yolk lecithin. The liposome particle size is 60-80 nm, the encapsulation rate is ≥80%, and the ethanol residue in the finished product is ≤0.5‰. The liposomal curcumin showed a release rate of <33% in simulated gastric fluid at pH 2.0 over 2 hours, and a release rate of >80% in simulated intestinal fluid at pH 7.4 over 4 hours.

[0009] Preferably, the nodular disease is one or more of thyroid nodules, breast nodules, and uterine fibroids. The composition achieves simultaneous auxiliary conditioning of multiple types of nodules by simultaneously intervening in four pathological mechanisms: inflammatory accumulation, endocrine disorders, oxidative stress damage, and immune imbalance. The intervention in inflammatory accumulation is achieved through the synergistic anti-inflammatory effect of liposomal curcumin and cardamom extract; the intervention in endocrine disorders is achieved through the regulation of estrogen metabolism pathway by myo-inositol; the intervention in oxidative stress damage is achieved through the synergistic antioxidant effect of liposomal curcumin and selenium; and the intervention in immune imbalance is achieved through the regulation of immune cell activity by selenium and the regulation of gut microbiota-mediated immune responses by inulin.

[0010] Preferably, the method for preparing the liposomal curcumin includes the following steps: Curcumin and food-grade phospholipids are dissolved in an ethanol solution with a volume fraction of 90%-95% at a mass ratio of 1:5-1:15. The ethanol is removed by rotary evaporation under a constant temperature water bath at 40-55℃ to form a uniform phospholipid film. Add phosphate buffer solution with pH 7.2-7.4 and hydrate for 30-60 min at a hydration temperature of 45-55℃ to obtain crude liposome suspension; The crude liposome suspension was homogenized 5-10 times in a high-pressure homogenizer at a pressure of 8000-12000psi, with the homogenization temperature controlled at 40-50℃, to obtain a liposome curcumin suspension with a particle size of 60-80nm. After being filtered and sterilized through a 0.22μm microporous membrane, liposomal curcumin powder was prepared by freeze-drying. The entire process was carried out in the dark. The encapsulation rate of the obtained liposomal curcumin was ≥80%, the ethanol residue of the finished product was ≤0.5‰, the release rate in simulated gastric fluid at pH 2.0 was <33% in 2 hours, and the release rate in simulated intestinal fluid at pH 7.4 was >80% in 4 hours.

[0011] Preferably, the inulin also serves as an auxiliary stabilizing component and a prebiotic functional component of the liposome wall material. During the liposome preparation process, inulin is compounded with phospholipids at a mass ratio of 1:0.5-1:2 and embedded in the liposome bilayer membrane structure, thereby increasing the rupture temperature of the liposome membrane by 8-12°C. Under storage conditions at 25°C, the liposome encapsulation rate decreases by <5% within 6 months. When used as a prebiotic, inulin can be selectively utilized by Bifidobacteria and Lactobacillus in the intestines, fermenting to produce short-chain fatty acids such as acetic acid, propionic acid, and butyric acid, which regulate intestinal pH and promote mineral absorption. At the same time, it regulates the functional state of distal organs through the gut-thyroid axis, gut-mammary axis, and gut-uterus axis, thus helping to enhance the treatment effect of nodules.

[0012] Preferably, the cardamom extract is an active extract obtained by water extraction or alcohol extraction of cardamom fruit, wherein the preparation method of the water extract is as follows: Grind the cardamom fruit into 20-40 mesh, add distilled water at a material-to-liquid ratio of 1:10-1:20, reflux at 90-100℃ for 2-3 times, 1-2 hours each time, combine the extracts, concentrate under reduced pressure to a relative density of 1.10-1.15 (60℃), and spray dry to obtain the water extract, which contains polysaccharides, amino acids, and water-soluble vitamins. The preparation method of the alcohol extract is as follows: Cardamom fruits were pulverized to 20-40 mesh and added to an ethanol solution with a volume fraction of 60%-70% at a material-to-liquid ratio of 1:8-1:15. The mixture was refluxed at 70-85℃ for 2-3 times, each time for 1.5-2.5 hours. The extracts were combined, and the ethanol was recovered under reduced pressure until no alcohol odor was detected. The extract was concentrated to a relative density of 1.08-1.12 (60℃) and then vacuum dried to obtain the alcohol extract, which contained volatile oil, flavonoids, and polyphenols. The volatile oil contained ≥30% 1,8-cineole and ≥15% α-terpineol. The flavonoids contained ≥8% quercetin derivatives. When the cardamom extract was synergistically combined with liposomal curcumin, the anti-inflammatory IC50 value of curcumin was reduced by 37.2%, showing a significant synergistic anti-inflammatory effect.

[0013] Preferably, the myo-inositol content in the composition is 100-1000 mg per part, preferably 300-800 mg, and most preferably 500 mg. Myo-inositol reduces the abnormal proliferation of thyroid follicular epithelial cells, mammary duct epithelial cells, and uterine smooth muscle cells by participating in the regulation of the phosphatidylinositol-3 kinase (PI3K) / protein kinase B (Akt) signaling pathway and inhibiting the excessive activation of downstream mammalian target of rapamycin (mTOR). Simultaneously, by regulating the activity of estrogen-metabolizing enzymes, promoting the conversion of estrone to estradiol, reducing excessively high estrogen levels, and improving endocrine disorders, the combined use of myo-inositol and liposomal curcumin can increase the cell proliferation inhibition rate by 42.6% compared to the myo-inositol-only group and by 39.8% compared to the liposomal curcumin-only group.

[0014] Preferably, the selenium element is added in the form of selenomethionine, sodium selenite or selenium yeast, and the content per part of selenium element is 20-100μg, preferably 40-80μg, and most preferably 60μg. When selenium yeast is selected as the selenium source, the organic selenium content in the selenium yeast is ≥98%, and the selenomethionine content is ≥85%. Selenium participates in the synthesis of selenium-containing enzymes such as glutathione peroxidase (GSH-Px) and thioredoxin reductase (TrxR), thereby clearing excess hydrogen peroxide and lipid peroxides in the body and reducing oxidative stress damage to cells. Simultaneously, by regulating the balance of Th1 / Th2 cytokines, it enhances the activity of natural killer cells (NK cells), thereby strengthening the body's immune surveillance and clearance capabilities against abnormally proliferating cells. When selenium is used in combination with liposomal curcumin, GSH-Px activity is increased by 28.5% compared to the selenium-only group and by 31.2% compared to the liposomal curcumin-only group. The level of the oxidative stress indicator MDA is reduced by 24.7% compared to the selenium-only group and by 27.3% compared to the liposomal curcumin-only group.

[0015] Preferably, the composition can be prepared as one of an oral liquid, a solid beverage, a soft capsule, or a tablet, and the preparation methods for each dosage form are as follows: Oral liquid dosage form: Liposome curcumin powder, inulin, cardamom extract, myo-inositol, selenium source, and purified water are mixed according to the formula ratio. 0.1%-0.3% of food-grade steviol glycosides are added as a sweetener, and 0.05%-0.1% of food-grade citric acid is added as a pH adjuster to adjust the pH to 6.5-7.0. After sterilization at 121℃ for 15-20 minutes, the mixture is filled to obtain an oral liquid. Each 10mL of oral liquid contains the equivalent of 1 part of the composition. Solid beverage dosage form: Liposome curcumin powder, inulin, cardamom extract, myo-inositol, selenium source, and food-grade maltodextrin are mixed according to the formula ratio. After wet granulation, drying, and granulation, the mixture is packaged to obtain a solid beverage. Each sachet of solid beverage contains the equivalent of 1 part of the composition. Soft capsule dosage form: Liposome curcumin suspension and soybean oil are mixed at a mass ratio of 1:2-1:5. Cardamom extract, myo-inositol and selenium source are added. After grinding evenly, it is used as the capsule material. Soft capsule shells are prepared with gelatin, glycerin and purified water at a mass ratio of 1:0.3:1. The soft capsules are then pressed to obtain soft capsules. Each soft capsule contains the equivalent of 1 part of the composition. Tablet Formulation: Liposome curcumin powder, inulin, cardamom extract, myo-inositol, selenium source, microcrystalline cellulose, and sodium carboxymethyl starch are mixed according to the formula ratio. 2%-5% of povidone K30 ethanol solution is added as a binder. After granulation, 0.5%-1% magnesium stearate is added as a lubricant. The mixture is then compressed into tablets, each containing an amount equivalent to one part of the composition. All dosage forms of the product were placed under accelerated testing conditions (40℃±2℃, RH75%±5%) for 6 months, and all quality indicators met food safety requirements. The liposome encapsulation rate decreased by less than 5%, and the release behavior showed no significant change.

[0016] As a preferred embodiment, the specific method of application is as follows: Take 1-2 doses of the composition daily for 3-6 months as one treatment cycle. Maintain a consistent daily intake during the treatment period. The composition achieves nodule treatment through the following synergistic mechanism: ① Liposome curcumin inhibits the activation of the nuclear factor-κB (NF-κB) signaling pathway, reduces the expression and release of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2), and clears accumulated inflammation in the body; ②Myo-inositol regulates the estrogen metabolism pathway, reduces the ratio of estradiol (E2) to progesterone (P) in serum, improves endocrine disorders, and inhibits abnormal cell proliferation. ③ Liposome curcumin and selenium synergistically enhance the activity of the antioxidant system, increase the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), reduce malondialdehyde (MDA) levels, and reduce oxidative stress damage to cells. ④ Selenium and inulin work together to regulate immune function, promote the secretion of Th1 cytokine interferon-γ (IFN-γ), inhibit the overexpression of Th2 cytokine IL-4, improve NK cell activity, and enhance the body's ability to clear abnormally proliferating cells. ⑤ Cardamom extract inhibits COX-2 activity and works synergistically with liposomal curcumin to exert anti-inflammatory effects, further enhancing the conditioning effect; ⑥ Inulin regulates the structure of intestinal flora, increases the abundance of beneficial bacteria such as Bifidobacteria and Lactobacillus, reduces the production and absorption of endotoxins, improves the microenvironment of the thyroid, breast, and uterus through the gut-organ axis, and blocks the progression of nodules.

[0017] Preferably, the evaluation indicators for the auxiliary conditioning effect include at least one of the following: ① Nodule volume change: The volume of thyroid nodules and breast nodules was measured by ultrasound imaging, and the volume of uterine fibroids was measured by gynecological ultrasound. After 3 months of continuous use, the nodule volume reduction rate was ≥15%, and after 6 months of continuous use, the nodule volume reduction rate was ≥30%. ② Changes in inflammatory factor levels: Serum TNF-α levels decreased by ≥25% compared to before conditioning, IL-6 levels decreased by ≥28%, and COX-2 levels decreased by ≥30%; ③ Changes in endocrine indicators: The serum E2 / P ratio decreased by ≥18% compared with before the treatment, and the ratio of follicle-stimulating hormone (FSH) to luteinizing hormone (LH) tended to be normal; ④ Changes in oxidative stress indicators: Serum SOD activity increased by ≥22% compared to before conditioning, GSH-Px activity increased by ≥25%, and MDA level decreased by ≥26%; ⑤ Changes in immune function indicators: Serum IFN-γ levels increased by ≥20% compared to before conditioning, IL-4 levels decreased by ≥22%, and NK cell activity increased by ≥18%; ⑥ Improvement in clinical symptoms: The scores of related symptoms such as neck discomfort, breast tenderness, and menstrual abnormalities decreased by ≥40% compared with before treatment, and the patients' quality of life scores improved by ≥35%.

[0018] The embodiments of the present invention have the following advantages due to the adoption of the above technical solutions: First, based on the TCM theory of "treating different diseases with the same method," this product targets the common pathogenesis of thyroid nodules, breast nodules, and uterine fibroids, which involve inflammatory accumulation, endocrine disorders, oxidative stress, and immune imbalance. Through the synergistic effects of multiple components—liposomal curcumin for potent anti-inflammatory and antioxidant effects, inositol for regulating endocrine metabolism, selenium for balancing immune function, cardamom extract for synergistic anti-inflammatory effects, and inulin for regulating intestinal microecology—this product achieves simultaneous auxiliary treatment of nodules in multiple organs. It overcomes the limitations of existing products that only target a single nodule, allowing the same product to cover three types of common nodules and reduce the burden of medication for patients.

[0019] Secondly, curcumin is encapsulated in phospholipid liposomes with a precise particle size of 60-80 nm. This particle size range avoids the problems of poor membrane stability and easy leakage associated with liposomes smaller than 60 nm, while overcoming the shortcomings of low transintestinal mucosal absorption efficiency and low lymphatic uptake associated with liposomes larger than 80 nm. Combined with its targeted release characteristics of low release in the stomach (<33%) and high release in the intestine (>80%), the oral bioavailability of curcumin is increased by 12.7 times compared to ordinary curcumin, the plasma half-life is extended to 4.3 times that of ordinary formulations, and the effective blood concentration is maintained for 8-12 hours, significantly enhancing its anti-inflammatory and antioxidant activities.

[0020] Third, by optimizing the phospholipid wall material ratio and preparation process, the liposome encapsulation rate is ≥80%, which is much higher than the 40%-70% of ordinary liposomes, reducing the loss of free curcumin and gastrointestinal irritation; the ethanol residue in the finished product is strictly controlled to ≤0.5‰, which meets the food-grade safety requirements and poses no safety risks for long-term use.

[0021] Fourth, there was a clear synergistic effect among the components: liposomal curcumin scavenged ROS, inhibited the NF-κB inflammatory pathway, and reduced the release of inflammatory factors; inositol downregulated estrogen receptor expression and improved endocrine disorders; selenium enhanced glutathione peroxidase activity and reduced oxidative damage; cardamom extract inhibited COX-2 activity and synergistically reduced inflammation; inulin promoted the production of short-chain fatty acids and regulated immunity and metabolism. The synergistic effect of these five components increased the nodule volume reduction rate by 68.3% compared to the curcumin-only group, increased the reduction in inflammatory factor levels by 52.7%, and improved endocrine regulation efficiency by 47.2%.

[0022] Fifth, the liposomes have a uniform particle size of 60-80nm (PDI≤0.2) and an absolute value of zeta potential ≥30mV, making them less prone to aggregation and precipitation during storage. Inulin, as an auxiliary component of the wall material, enhances the mechanical strength of the liposome membrane. Accelerated tests (40℃±2℃, RH75%±5%) show that the liposome encapsulation rate decreases by <5% within 6 months, and the release behavior does not change significantly, making them suitable for industrial production and long-term storage.

[0023] Sixth, all raw materials are food-grade or new food ingredients, with no toxic side effects. Long-term use does not pose a risk of liver or kidney damage. It is suitable for daily auxiliary conditioning for patients with various nodular diseases, especially for those who do not want to undergo surgery or to prevent recurrence after surgery, filling the gap of lack of effective intervention methods during the period of regular clinical observation.

[0024] Seventh, it can be prepared into various dosage forms such as oral liquid, solid beverage, and soft capsules. It can be taken regularly at a fixed time every day without any special operation. Patient compliance is high, making it easy to adhere to long-term conditioning and ensuring the sustainability of conditioning effects.

[0025] The above overview is for illustrative purposes only and is not intended to be limiting in any way. In addition to the illustrative aspects, embodiments, and features described above, further aspects, embodiments, and features of the invention will become readily apparent from the accompanying drawings and the following detailed description. Attached Figure Description

[0026] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0027] Figure 1 This is a flowchart illustrating the preparation process of the liposomal curcumin of the present invention. Figure 2 This is a flow chart of the oral liquid dosage form preparation process of the present invention; Figure 3 This is a flow chart of the solid beverage dosage form preparation process of the present invention; Figure 4 This is a flow chart of the soft capsule dosage form preparation process of the present invention; Figure 5 This is a flowchart of the tablet dosage form preparation process of the present invention. Detailed Implementation

[0028] In the following description, only certain exemplary embodiments are briefly described. As those skilled in the art will recognize, the described embodiments can be modified in various ways without departing from the spirit or scope of the invention. Therefore, the drawings and description are considered to be exemplary in nature and not restrictive.

[0029] The embodiments of the present invention will now be described in detail with reference to the accompanying drawings.

[0030] Example 1: Preparation and application of oral liquid liposomal curcumin composition

[0031] 1. Raw material preparation

[0032] Liposome curcumin: Using soybean lecithin as the wall material, curcumin and soybean lecithin were dissolved in a 95% ethanol solution at a mass ratio of 1:10. The ethanol was removed by rotary evaporation in a 50°C constant temperature water bath to form a uniform phospholipid film. Phosphate buffer solution at pH 7.4 was added and hydrated for 45 min at a hydration temperature of 50°C to obtain a crude liposome suspension. The crude liposome suspension was homogenized 8 times at 10000 psi pressure and 45°C using a high-pressure homogenizer to obtain a liposome curcumin suspension with a particle size of 65 nm. After filtration through a 0.22 μm microporous membrane for sterilization, the liposome curcumin powder was freeze-dried. The encapsulation rate was 86.3%, the ethanol residue in the finished product was 0.32‰, the release rate was 28.7% in simulated gastric juice at pH 2.0 after 2 h, and the release rate was 87.5% in simulated intestinal juice at pH 7.4 after 4 h.

[0033] Inulin: Select chicory inulin with a degree of polymerization of 2-60 and a purity of ≥95%.

[0034] Cardamom extract: The extract obtained by reflux extraction with 60% ethanol was tested and found to contain 12.3% volatile oil (including 32.7% 1,8-cineole and 16.2% α-terpineol), and 9.1% quercetin derivatives among the flavonoids.

[0035] myo-inositol: purity ≥99%.

[0036] Selenium source: Selenium yeast is selected, with an organic selenium content of 98.7% and a selenomethionine content of 87.3%, calculated as elemental selenium.

[0037] 2. Preparation of oral liquid

[0038] Weigh the following raw materials according to the dosage for each serving: liposomal curcumin powder (containing 50 mg curcumin), 5 g inulin, 40 mg cardamom extract, 500 mg myo-inositol, and 60 μg selenium yeast (calculated as selenium). Mix the above raw materials with 900 mL of purified water, add 0.2% steviol glycosides and 0.08% citric acid, stir to dissolve, adjust the pH to 6.8 with citrate-disodium hydrogen phosphate buffer, add purified water to 1000 mL, sterilize at 121 °C for 20 min, and fill into 10 mL bottles to obtain oral liquid, each bottle containing the equivalent of 1 serving of the composition.

[0039] 3. Quality inspection data

[0040] Table 1. Quality test data of the oral liquid in Example 1

[0041] Table 2 Accelerated stability test data of oral liquid in Example 1 (40℃±2℃, RH75%±5%)

[0042] 4. Application effect verification

[0043] Sixty female volunteers diagnosed with thyroid nodules (0.5-1.0 cm in diameter), breast nodules (BI-RADS 3, 0.4-0.9 cm in diameter), or uterine fibroids (1.0-2.5 cm in diameter) were selected. They took one bottle of the oral solution from Example 1 twice daily, morning and evening, for six consecutive months. Changes in relevant indicators were monitored, and the results are shown in the table below: Table 3: Efficacy data of the composition of Example 1 in treating nodules (n=60)

[0044] Example 2: Preparation and application of liposomal curcumin compositions in solid beverage formulations

[0045] 1. Raw material preparation

[0046] Liposome curcumin: Using sunflower lecithin as the wall material, curcumin and sunflower lecithin were dissolved in a 92% ethanol solution at a mass ratio of 1:12. The ethanol was removed by rotary evaporation in a constant temperature water bath at 48℃ to form a uniform phospholipid film. Phosphate buffer solution at pH 7.3 was added for 50 min of hydration at 48℃ to obtain a crude liposome suspension. The crude liposome suspension was homogenized 9 times at 9000psi pressure and 42℃ using a high-pressure homogenizer to obtain a liposome curcumin suspension with a particle size of 72nm. After filtration through a 0.22μm microporous membrane for sterilization, the liposome curcumin powder was freeze-dried. The encapsulation rate was 84.7%, the residual ethanol in the finished product was 0.41‰, the release rate was 30.2% in simulated gastric juice at pH 2.0 after 2 h, and the release rate was 85.3% in simulated intestinal juice at pH 7.4 after 4 h.

[0047] Inulin: Chicory inulin with a degree of polymerization of 2-60 and a purity of ≥95% is selected and compounded with sunflower lecithin at a mass ratio of 1:1 as a liposome wall material.

[0048] Cardamom extract: The water extract was tested and found to contain 62.3% polysaccharides, 18.7% amino acids, and 7.2% water-soluble vitamins.

[0049] myo-inositol: purity ≥99%.

[0050] Selenium source: selenomethionine with a purity of ≥98% is selected, calculated as elemental selenium.

[0051] 2. Preparation of solid beverages

[0052] Weigh the following ingredients per serving: liposome curcumin powder (containing 50mg curcumin), 8g inulin, 60mg cardamom extract, 700mg myo-inositol, and 80μg selenomethionine (calculated as selenium). Mix the above ingredients with 150g of food-grade maltodextrin, add 5% povidone K30 ethanol solution as a binder, wet granulate, dry at 60℃ for 2h, and after granulation, package into solid beverages containing one serving of the composition per bag, with a net weight of 12g per bag.

[0053] 3. Quality inspection data

[0054] Table 4 Quality test data of solid beverage in Example 2

[0055] Table 5. Accelerated stability test data of solid beverage in Example 2 (40℃±2℃, RH75%±5%)

[0056] 4. Application effect verification

[0057] Sixty female volunteers diagnosed with thyroid nodules (0.6-1.1 cm in diameter), breast nodules (BI-RADS 3, 0.5-1.0 cm in diameter), or uterine fibroids (1.2-2.8 cm in diameter) were selected. They took one sachet of the solid beverage from Example 2 twice daily, morning and evening, with warm water for six consecutive months. Changes in relevant indicators were monitored, and the results are shown in the table below: Table 6: Efficacy data of the composition of Example 2 in treating nodules (n=60)

[0058] Table 7. In vitro release data after solid beverage was consumed in Example 2.

[0059] Example 3: Preparation and application of liposomal curcumin compositions in soft capsule form

[0060] 1. Raw material preparation

[0061] Liposome curcumin: Using egg yolk lecithin as the wall material, curcumin and egg yolk lecithin were dissolved in 94% ethanol solution at a mass ratio of 1:8. The ethanol was removed by rotary evaporation in a constant temperature water bath at 52℃ to form a uniform phospholipid film. Phosphate buffer solution at pH 7.2 was added and hydrated for 40 min at a hydration temperature of 52℃ to obtain a crude liposome suspension. The crude liposome suspension was homogenized 7 times at 11000 psi pressure and 48℃ using a high-pressure homogenizer to obtain a liposome curcumin suspension with a particle size of 78 nm. After filtration and sterilization through a 0.22 μm microporous membrane, it was stored for later use. The encapsulation rate was tested to be 82.5%, the residual ethanol in the finished product was 0.47‰, the release rate was 32.1% in simulated gastric juice at pH 2.0 after 2 h, and the release rate was 82.7% in simulated intestinal juice at pH 7.4 after 4 h.

[0062] Inulin: Select chicory inulin with a degree of polymerization of 2-60 and a purity of ≥95%.

[0063] Cardamom extract: The extract was obtained by reflux extraction with 70% ethanol. It was found to contain 13.1% volatile oil (including 33.2% 1,8-cineole and 16.5% α-terpineol) and 9.5% quercetin derivatives among the flavonoids.

[0064] myo-inositol: purity ≥99%.

[0065] Selenium source: Sodium selenite with a purity of ≥99% is selected, calculated as elemental selenium.

[0066] 2. Soft Capsule Preparation

[0067] Weigh the following raw materials according to the measured amount per part: liposome curcumin suspension (containing 50mg curcumin), 3g inulin, 20mg cardamom extract, 300mg myo-inositol, and 40μg sodium selenite (calculated as selenium). Mix the above raw materials with 100g soybean oil and grind them evenly to obtain the contents of the capsule. Prepare the soft capsule shell with a mass ratio of gelatin:glycerin:purified water = 1:0.3:1, and press it to obtain a soft capsule containing 1 part of the composition per capsule, with each soft capsule weighing 0.8g.

[0068] 3. Quality inspection data

[0069] Table 8 Quality test data of soft capsules in Example 3

[0070] Table 9 Accelerated stability test data of soft capsules in Example 3 (40℃±2℃, RH75%±5%)

[0071] 4. Application effect verification

[0072] Sixty female volunteers diagnosed with thyroid nodules (0.5-1.0 cm in diameter), breast nodules (BI-RADS 3, 0.4-0.9 cm in diameter), or uterine fibroids (1.0-2.5 cm in diameter) were selected. They took one soft capsule of Example 3 twice daily, morning and evening, for six consecutive months. Changes in relevant indicators were monitored, and the results are shown in the table below: Table 10: Efficacy data of the composition of Example 3 in treating nodules (n=60)

[0073] Table 11 Dissolution data of soft capsules in Example 3 (paddle method, rotation speed 100 rpm)

[0074] Comparative Example 1: The conditioning effect of ordinary curcumin composition (without liposomes)

[0075] To verify the superiority of the liposome process, Comparative Example 1 was set up. The composition formulation was the same as that in Example 1, but the curcumin was not encapsulated by liposomes and was instead ordinary curcumin powder, prepared as an oral liquid dosage form. Sixty volunteers with the same inclusion criteria were selected, and the dosage was the same as in Example 1. They took the medicine continuously for 6 months, and the changes in relevant indicators are shown in the table below: Table 12 Modulation effect data of ordinary curcumin composition in Comparative Example 1 (n=60)

[0076] As shown in Table 12, the conditioning effect of ordinary curcumin composition is significantly lower than that of the liposomal curcumin composition of the present invention, which verifies the key role of liposomal process in improving the bioavailability of curcumin and enhancing the conditioning effect.

[0077] Comparative Example 2: Therapeutic Effects of Compositions Lacking Cardamom Extract

[0078] Comparative Example 2 was set up with the same composition formulation as Example 1, but without cardamom extract. It was prepared as an oral liquid dosage form, and 60 volunteers with the same inclusion criteria were selected. The dosage was the same as in Example 1, and the volunteers took the medication continuously for 6 months. The changes in relevant indicators are shown in the table below: Table 13 Conditioning effect data of the composition without cardamom extract in Comparative Example 2 (n=60)

[0079] As shown in Table 13, the anti-inflammatory and nodule-shrinking effects of the composition were significantly reduced after the cardamom extract was omitted, which verifies the synergistic effect of cardamom extract and other components.

[0080] Comparative Example 3: Conditioning Effects of Compositions Lacking Inositol

[0081] Comparative Example 3 was set up with the same composition formulation as Example 1, but without myo-inositol. It was prepared as an oral liquid dosage form. Sixty volunteers with the same inclusion criteria were selected and took the same dosage as in Example 1 for 6 consecutive months. The changes in relevant indicators are shown in the table below: Table 14 Conditioning effect data of the composition without myo-inositol in Comparative Example 3 (n=60)

[0082] As shown in Table 14, the composition's ability to regulate endocrine function and inhibit cell proliferation decreased after the absence of inositol, verifying the key role of myo-inositol in regulating endocrine function and inhibiting abnormal proliferation.

[0083] Comparative Example 4: Therapeutic Effects of Compositions Lacking Selenium

[0084] Comparative Example 4 was set up with the same composition formulation as Example 1, but without selenium. It was prepared as an oral liquid dosage form. Sixty volunteers with the same inclusion criteria were selected and took the same dosage as in Example 1 for 6 consecutive months. The changes in relevant indicators are shown in the table below: Table 15 Conditioning effect data of the composition lacking selenium in Comparative Example 4 (n=60)

[0085] As shown in Table 15, the antioxidant and immunomodulatory capabilities of the composition decreased after the selenium element was missing, which verifies the key role of selenium in enhancing antioxidant capacity and regulating immunity.

[0086] Comparative Example 5: Therapeutic Effects of Compositions with Liposome Particle Sizes Not in the 60-80 nm Range

[0087] Comparative Example 5 was set up with liposomes of 95 nm in diameter (greater than 80 nm). The rest of the formulation and preparation process were the same as in Example 1. The preparation was an oral liquid dosage form. Sixty volunteers with the same inclusion criteria were selected and took the same dosage as in Example 1 for 6 consecutive months. The changes in relevant indicators are shown in the table below: Table 16 Conditioning effect data of the composition with liposomes of 95 nm in diameter in Comparative Example 5 (n=60)

[0088] As shown in Table 16, when the liposome particle size is greater than 80 nm, the oral bioavailability of curcumin decreases significantly and the conditioning effect is significantly reduced, which verifies the importance of the 60-80 nm particle size range for improving the absorption efficiency of liposomes.

[0089] Comparative Example 6: Therapeutic Effects of Compositions with Liposome Encapsulation Rate <80%

[0090] Comparative Example 6 was set up, and the liposome encapsulation rate was optimized to 65% (<80%). The rest of the formulation was the same as in Example 1. It was prepared as an oral liquid dosage form. Sixty volunteers with the same inclusion criteria were selected and took the same dosage as in Example 1 for 6 consecutive months. The changes in relevant indicators are shown in the table below: Table 17 Conditioning effect data of the composition with 65% liposome encapsulation rate in Comparative Example 6 (n=60)

[0091] As shown in Table 17, when the liposome encapsulation rate is <80%, the free curcumin content increases, which not only reduces the absorption of the active ingredient but also increases the incidence of gastrointestinal adverse reactions, verifying the importance of an encapsulation rate ≥80% in ensuring efficacy and safety.

[0092] The above examples and comparative examples fully verify the excellent performance of the composition of the present invention. Each component exerts a synergistic effect under specific ratios and process conditions, achieving simultaneous and efficient auxiliary treatment of thyroid nodules, breast nodules, and uterine fibroids. Moreover, the product has stable quality and high safety, making it suitable for industrial production and application.

[0093] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any person skilled in the art can easily conceive of various variations or substitutions within the technical scope disclosed in the present invention, and these should all be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. A composition for the adjunctive treatment of nodular diseases, characterized in that, Composed of the following ingredients, measured per serving: Liposome curcumin (60-80nm), inulin 3-10g, cardamom (Elettaria cardamomum) extract 10-80mg, myo-inositol 100-1000mg, selenium 20-100μg; The selenium element is derived from one or more of selenomethionine, sodium selenite, and selenium yeast. The liposome curcumin is prepared using food-grade phospholipids. The phospholipid wall material is selected from one or more of soybean lecithin, sunflower lecithin, and egg yolk lecithin. The liposome particle size is 60-80 nm, the encapsulation rate is ≥80%, and the ethanol residue in the finished product is ≤0.5‰. The liposomal curcumin showed a release rate of <33% in simulated gastric fluid at pH 2.0 over 2 hours and a release rate of >80% in simulated intestinal fluid at pH 7.4 over 4 hours.

2. The composition for adjuvant treatment of nodular diseases according to claim 1, characterized in that, The nodular diseases mentioned are one or more of thyroid nodules, breast nodules, and uterine fibroids. The composition achieves simultaneous auxiliary conditioning of multiple types of nodules by simultaneously intervening in four pathological mechanisms: inflammatory accumulation, endocrine disorders, oxidative stress damage, and immune imbalance. The intervention in inflammatory accumulation is achieved through the synergistic anti-inflammatory effect of liposomal curcumin and cardamom extract. The intervention in endocrine disorders is achieved through the regulation of estrogen metabolism pathway by myo-inositol. The intervention in oxidative stress damage is achieved through the synergistic antioxidant effect of liposomal curcumin and selenium. The intervention in immune imbalance is achieved through the regulation of immune cell activity by selenium and the regulation of gut microbiota-mediated immune response by inulin.

3. The composition for adjuvant treatment of nodular diseases according to claim 1, characterized in that, The method for preparing the liposomal curcumin includes the following steps: Curcumin and food-grade phospholipids are dissolved in an ethanol solution with a volume fraction of 90%-95% at a mass ratio of 1:5-1:

15. The ethanol is removed by rotary evaporation under a constant temperature water bath at 40-55℃ to form a uniform phospholipid film. Add phosphate buffer solution with pH 7.2-7.4 and hydrate for 30-60 min at a hydration temperature of 45-55℃ to obtain crude liposome suspension; The crude liposome suspension was homogenized 5-10 times in a high-pressure homogenizer at a pressure of 8000-12000psi, with the homogenization temperature controlled at 40-50℃, to obtain a liposome curcumin suspension with a particle size of 60-80nm. After being filtered and sterilized through a 0.22μm microporous membrane, liposomal curcumin powder was prepared by freeze-drying. The entire process was carried out in the dark. The encapsulation rate of the obtained liposomal curcumin was ≥80%, the ethanol residue of the finished product was ≤0.5‰, the release rate in simulated gastric fluid at pH 2.0 was <33% in 2 hours, and the release rate in simulated intestinal fluid at pH 7.4 was >80% in 4 hours.

4. The composition for adjuvant treatment of nodular diseases according to claim 1, characterized in that, The inulin serves as both an auxiliary stabilizing component and a prebiotic functional component for the liposome wall material. During liposome preparation, inulin is compounded with phospholipids at a mass ratio of 1:0.5-1:2 and embedded in the liposome bilayer membrane structure, thereby increasing the rupture temperature of the liposome membrane by 8-12°C. Under storage conditions at 25°C, the liposome encapsulation rate decreases by less than 5% within 6 months. When used as a prebiotic, inulin can be selectively utilized by Bifidobacteria and Lactobacillus in the intestines, fermenting to produce short-chain fatty acids such as acetic acid, propionic acid, and butyric acid, which regulate intestinal pH and promote mineral absorption. At the same time, it regulates the functional state of distal organs through the gut-thyroid axis, gut-mammary axis, and gut-uterus axis, thus helping to enhance the treatment effect of nodules.

5. The composition for adjuvant treatment of nodular diseases according to claim 1, characterized in that, The cardamom extract is an active extract obtained from cardamom fruit through water extraction or alcohol extraction, wherein the preparation method of the water extract is as follows: Grind the cardamom fruit into 20-40 mesh, add distilled water at a material-to-liquid ratio of 1:10-1:20, reflux at 90-100℃ for 2-3 times, 1-2 hours each time, combine the extracts, concentrate under reduced pressure to a relative density of 1.10-1.15 (60℃), and spray dry to obtain the water extract, which contains polysaccharides, amino acids, and water-soluble vitamins. The preparation method of the alcohol extract is as follows: Cardamom fruits were pulverized to 20-40 mesh and added to an ethanol solution with a volume fraction of 60%-70% at a material-to-liquid ratio of 1:8-1:

15. The mixture was refluxed at 70-85℃ for 2-3 times, each time for 1.5-2.5 hours. The extracts were combined, and the ethanol was recovered under reduced pressure until no alcohol odor was detected. The extract was concentrated to a relative density of 1.08-1.12 (60℃) and then vacuum dried to obtain the alcohol extract, which contained volatile oil, flavonoids, and polyphenols. The volatile oil contained ≥30% 1,8-cineole and ≥15% α-terpineol. The flavonoids contained ≥8% quercetin derivatives. When the cardamom extract was synergistically combined with liposomal curcumin, the anti-inflammatory IC50 value of curcumin was reduced by 37.2%, showing a significant synergistic anti-inflammatory effect.

6. The composition for adjuvant treatment of nodular diseases according to claim 1, characterized in that, The myo-inositol content in the composition is 100-1000 mg per part, preferably 300-800 mg, and most preferably 500 mg. Myo-inositol participates in the regulation of the phosphatidylinositol-3 kinase (PI3K) / protein kinase B (Akt) signaling pathway, inhibits the excessive activation of the downstream mammalian target of rapamycin (mTOR), thereby reducing the abnormal proliferation of thyroid follicular epithelial cells, mammary duct epithelial cells, and uterine smooth muscle cells. Simultaneously, by regulating the activity of estrogen-metabolizing enzymes, promoting the conversion of estrone to estradiol, reducing excessively high estrogen levels, and improving endocrine disorders, the combined use of myo-inositol and liposomal curcumin can increase the cell proliferation inhibition rate by 42.6% compared to the myo-inositol-only group and by 39.8% compared to the liposomal curcumin-only group.

7. The composition for adjuvant treatment of nodular diseases according to claim 1, characterized in that, The selenium element is added in the form of selenomethionine, sodium selenite or selenium yeast, and the content per part is 20-100μg, preferably 40-80μg, and most preferably 60μg; When selenium yeast is selected as the selenium source, the organic selenium content in the selenium yeast is ≥98%, and the selenomethionine content is ≥85%. Selenium participates in the synthesis of selenium-containing enzymes such as glutathione peroxidase (GSH-Px) and thioredoxin reductase (TrxR), thereby clearing excess hydrogen peroxide and lipid peroxides in the body and reducing oxidative stress damage to cells. Simultaneously, by regulating the balance of Th1 / Th2 cytokines, it enhances the activity of natural killer cells (NK cells), thereby strengthening the body's immune surveillance and clearance capabilities against abnormally proliferating cells. When selenium is used in combination with liposomal curcumin, GSH-Px activity is increased by 28.5% compared to the selenium-only group and by 31.2% compared to the liposomal curcumin-only group. The level of the oxidative stress indicator MDA is reduced by 24.7% compared to the selenium-only group and by 27.3% compared to the liposomal curcumin-only group.

8. The composition for adjuvant treatment of nodular diseases according to claim 1, characterized in that, The composition can be prepared as one of the following dosage forms: oral liquid, solid beverage, soft capsule, or tablet. The preparation methods for each dosage form are as follows: Oral liquid dosage form: Liposome curcumin powder, inulin, cardamom extract, myo-inositol, selenium source, and purified water are mixed according to the formula ratio. 0.1%-0.3% of food-grade steviol glycosides are added as a sweetener, and 0.05%-0.1% of food-grade citric acid is added as a pH adjuster to adjust the pH to 6.5-7.

0. After sterilization at 121℃ for 15-20 minutes, the mixture is filled to obtain an oral liquid. Each 10mL of oral liquid contains the equivalent of 1 part of the composition. Solid beverage dosage form: Liposome curcumin powder, inulin, cardamom extract, myo-inositol, selenium source, and food-grade maltodextrin are mixed according to the formula ratio. After wet granulation, drying, and granulation, the mixture is packaged to obtain a solid beverage. Each sachet of solid beverage contains the equivalent of 1 part of the composition. Soft capsule dosage form: Liposome curcumin suspension and soybean oil are mixed at a mass ratio of 1:2-1:

5. Cardamom extract, myo-inositol and selenium source are added. After grinding evenly, it is used as the capsule material. Soft capsule shells are prepared with gelatin, glycerin and purified water at a mass ratio of 1:0.3:

1. The soft capsules are then pressed to obtain soft capsules. Each soft capsule contains the equivalent of 1 part of the composition. Tablet Formulation: Liposome curcumin powder, inulin, cardamom extract, myo-inositol, selenium source, microcrystalline cellulose, and sodium carboxymethyl starch are mixed according to the formula ratio. 2%-5% of povidone K30 ethanol solution is added as a binder. After granulation, 0.5%-1% magnesium stearate is added as a lubricant. The mixture is then compressed into tablets, each containing an amount equivalent to one part of the composition. All dosage forms of the product were placed under accelerated testing conditions (40℃±2℃, RH75%±5%) for 6 months, and all quality indicators met food safety requirements. The liposome encapsulation rate decreased by less than 5%, and the release behavior showed no significant change.

9. The use of the composition for assisting in the treatment of nodular diseases according to any one of claims 1-8 in the preparation of health foods for assisting in the treatment of thyroid nodules, breast nodules, and uterine fibroids, characterized in that, The specific method of application is as follows: Take 1-2 doses of the composition daily for 3-6 months as one treatment cycle. Maintain a consistent daily intake during the treatment period. The composition achieves nodule treatment through the following synergistic mechanism: ① Liposome curcumin inhibits the activation of the nuclear factor-κB (NF-κB) signaling pathway, reduces the expression and release of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2), and clears accumulated inflammation in the body; ②Myo-inositol regulates the estrogen metabolism pathway, reduces the ratio of estradiol (E2) to progesterone (P) in serum, improves endocrine disorders, and inhibits abnormal cell proliferation. ③ Liposome curcumin and selenium synergistically enhance the activity of the antioxidant system, increase the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), reduce malondialdehyde (MDA) levels, and reduce oxidative stress damage to cells. ④ Selenium and inulin work together to regulate immune function, promote the secretion of Th1 cytokine interferon-γ (IFN-γ), inhibit the overexpression of Th2 cytokine IL-4, improve NK cell activity, and enhance the body's ability to clear abnormally proliferating cells. ⑤ Cardamom extract inhibits COX-2 activity and works synergistically with liposomal curcumin to exert anti-inflammatory effects, further enhancing the conditioning effect; ⑥ Inulin regulates the structure of intestinal flora, increases the abundance of beneficial bacteria such as Bifidobacteria and Lactobacillus, reduces the production and absorption of endotoxins, improves the microenvironment of the thyroid, breast, and uterus through the gut-organ axis, and blocks the progression of nodules.

10. The application according to claim 9, characterized in that, The evaluation indicators for the auxiliary conditioning effect include at least one of the following: ① Nodule volume change: The volume of thyroid nodules and breast nodules was measured by ultrasound imaging, and the volume of uterine fibroids was measured by gynecological ultrasound. After 3 months of continuous use, the nodule volume reduction rate was ≥15%, and after 6 months of continuous use, the nodule volume reduction rate was ≥30%. ② Changes in inflammatory factor levels: Serum TNF-α levels decreased by ≥25% compared to before conditioning, IL-6 levels decreased by ≥28%, and COX-2 levels decreased by ≥30%; ③ Changes in endocrine indicators: The serum E2 / P ratio decreased by ≥18% compared with before the treatment, and the ratio of follicle-stimulating hormone (FSH) to luteinizing hormone (LH) tended to be normal; ④ Changes in oxidative stress indicators: Serum SOD activity increased by ≥22% compared to before conditioning, GSH-Px activity increased by ≥25%, and MDA level decreased by ≥26%; ⑤ Changes in immune function indicators: Serum IFN-γ levels increased by ≥20% compared to before conditioning, IL-4 levels decreased by ≥22%, and NK cell activity increased by ≥18%; ⑥ Improvement in clinical symptoms: The scores of related symptoms such as neck discomfort, breast tenderness, and menstrual abnormalities decreased by ≥40% compared with before treatment, and the patients' quality of life scores improved by ≥35%.

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