Pharmaceutical compositions, formulations and uses thereof for the treatment of mastitis

Abstract

This invention relates to the field of pharmaceutical preparation technology, specifically to a pharmaceutical composition, preparation, and application for treating plasma cell mastitis. The first aspect of this invention provides a pharmaceutical composition for treating plasma cell mastitis, which is made from the following medicinal materials in parts by weight: Bupleurum chinense 10-15 parts, Paeonia lactiflora 10-20 parts, Taraxacum mongolicum 15-30 parts, Forsythia suspensa 10-15 parts, Uncaria rhynchophylla 10-20 parts, Trichosanthes kirilowii 15-25 parts, Pinellia ternata 6-12 parts, Sinapis alba 6-12 parts, Citrus reticulata 6-12 parts, Poria cocos 10-20 parts, Salvia miltiorrhiza 10-20 parts, Paeonia suffruticosa 5-15 parts, Paeonia lactiflora 10-15 parts, Gleditsia sinensis thorns 6-12 parts, and Cervi cornu colla 6-12 parts. The second aspect provides a traditional Chinese medicine phospholipid complex nanoparticle, which is obtained by nanoemulsification of a fluid extract prepared from the above composition with phospholipids. The formula of this invention can work during the mass stage of plasma cell mastitis and effectively inhibit the further evolution of the mass into an abscess stage. The nanoparticles can enhance the absorption and targeting of the lipid-soluble components.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical formulation technology, specifically relating to a pharmaceutical composition, formulation, and application for treating plasma cell mastitis. Background Technology

[0002] Plasma cell mastitis (PCM) is a nonbacterial, non-lactational breast disease characterized by mammary duct ectasia and chronic periductal inflammation. It commonly affects non-lactational or premenopausal women aged 30-40, accounting for approximately 4%–5% of benign breast diseases, and its incidence has been increasing in recent years. Its core pathological feature is extensive periductal infiltration of plasma cells, accompanied by aggregations of lymphocytes, neutrophils, and multinucleated giant cells, with plasma cells being the predominant group. As terminally differentiated B lymphocytes, plasma cells' differentiation and survival are highly dependent on the activation of the IL-6-mediated JAK2 / STAT3 signaling pathway. This pathway not only promotes B cell differentiation into plasma cells but also inhibits plasma cell apoptosis by inducing the expression of the anti-apoptotic protein Bcl-2, thus leading to persistent and difficult-to-limit local inflammation.

[0003] Clinically, plasma cell mastitis often presents as a mass stage (primarily a painless or dull-ache breast mass with indistinct borders, easily misdiagnosed as breast cancer) and an abscess stage (the mass softens, ruptures, and forms sinus tracts or fistulas). Currently, the main treatment in Western medicine is surgical resection, but the recurrence rate is high, and some patients require repeated surgeries or even total mastectomy, placing a heavy burden on their physical and mental well-being. Therefore, seeking safe and effective non-surgical treatment strategies has become an urgent clinical need.

[0004] In the field of traditional Chinese medicine, benign diseases such as breast hyperplasia are often treated with formulas and medicines that have the effects of dispersing lumps, resolving blood stasis, and unblocking collaterals. For example, Xiaoru Sanjie capsules have been widely used in breast hyperplasia with good safety. However, research on specific traditional Chinese medicine compound formulas for plasma cell mastitis (especially in the mass stage and the early stage of the mass evolving into an abscess) is still relatively lacking. On the one hand, the number of formulas reported in the current literature that can target this stage (such as plasma cell infiltration and periductal inflammation) is limited. On the other hand, even if a few formulas have a certain effect in dispersing lumps, their therapeutic effects in inhibiting abnormal plasma cell aggregation, controlling the inflammatory process, and preventing abscess formation still need to be improved.

[0005] Furthermore, current TCM treatments mostly employ traditional decoctions or conventional capsule formulations, resulting in a relatively limited range of methods. With advancements in pharmaceutical technology, combining TCM formulas with suitable excipients to create complex TCM preparations with sustained-release, targeted, or enhanced-penetration properties (such as gel patches, microemulsion drug delivery systems, and nanocomposite hydrogels) may enhance efficacy by improving local drug concentration, prolonging the duration of action, and increasing bioavailability. However, research on the synergistic effects of TCM-excipient composite preparations in the local treatment of plasma cell mastitis is scarce, and whether they can more effectively intervene in the development of inflammation during the mass stage and prevent abscess formation remains a blank.

[0006] Therefore, developing a traditional Chinese medicine compound that targets the pathological characteristics of the mass stage of plasma cell mastitis, effectively inhibits plasma cell infiltration and inflammation development, and can enhance local efficacy through formulation technology innovation has significant clinical significance and research value. Summary of the Invention

[0007] To address the shortcomings of existing technologies, the first aspect of this invention provides a pharmaceutical composition for treating plasma cell mastitis, the composition being made from the following medicinal materials in parts by weight: Bupleurum chinense 10-15 parts, Paeonia lactiflora 10-20 parts, Taraxacum mongolicum 15-30 parts, Forsythia suspensa 10-15 parts, Uncaria rhynchophylla 10-20 parts, Trichosanthes kirilowii 15-25 parts, Pinellia ternata 6-12 parts, Sinapis alba 6-12 parts, Citrus reticulata 6-12 parts, Poria cocos 10-20 parts, Salvia miltiorrhiza 10-20 parts, Paeonia suffruticosa 5-15 parts, Paeonia lactiflora 10-15 parts, Gleditsia sinensis thorns 6-12 parts, and Cervi cornu colla 6-12 parts.

[0008] The traditional Chinese medicine compound provided by this invention is derived from traditional formulas for eliminating breast lumps and dispersing nodules through modifications. The core treatment principle of this formula is to soothe the liver and clear heat, resolve phlegm and remove blood stasis, and promote detoxification and eliminate carbuncles, thus better aligning with the complex pathogenesis of plasma cell mastitis in its lumpy stage and early development. This self-formulated compound, based on soothing the liver, strengthens heat-clearing and detoxification to suppress heat toxicity, and introduces detoxification and carbuncle-dispersing for early intervention, preventing abscess formation. This allows the formula to not only function effectively during the lumpy stage of plasma cell mastitis but also effectively prevent the lump from further evolving into an abscess. Furthermore, considering that plasma cell mastitis lumps are often yin-type carbuncles and phlegm nodules, this formula shifts from the traditional approach of using salty and soft herbs to a warm and pungent approach that regulates qi and invigorates blood to resolve phlegm and disperse nodules. Specifically, the principal herbs in the formula are Bupleurum, White Peony Root, Dandelion, Forsythia, and Uncaria. Bupleurum soothes the liver and relieves depression, while White Peony Root nourishes blood, softens the liver, and relieves pain. The combination of these two herbs regulates qi, providing a foundation for treating the root cause. The combination of dandelion, forsythia, and cat's claw herb clears heat and detoxifies, reduces swelling and dissipates nodules, directly eliminating heat toxins, making it an essential medicine for treating carbuncles. The assistant herbs are trichosanthes fruit, prepared pinellia tuber, white mustard seed, tangerine peel, poria cocos, salvia miltiorrhiza, peony bark, and red peony root. Trichosanthes fruit and prepared pinellia tuber soothe the chest, resolve phlegm, and dissipate nodules; white mustard seed effectively eliminates phlegm both under the skin and on the membranes; tangerine peel and poria cocos regulate qi, strengthen the spleen, and dispel dampness, preventing phlegm production at its source. This group of assistant herbs specializes in resolving phlegm and dissipating nodules. The combination of salvia miltiorrhiza, peony bark, and red peony root cools the blood, invigorates blood circulation, removes blood stasis, and relieves pain, thus reducing the stagnation of swelling. The adjuvant herbs are soapberry thorn and deer antler glue. Soapberry thorn invigorates blood circulation, reduces swelling, promotes pus drainage, and is an essential medicine for carbuncles, thus targeting the early symptoms of pus formation; deer antler glue warms and nourishes essence and blood, assists yang internally, and in this formula, its warming and unblocking properties, combined with the large amount of heat-clearing and phlegm-resolving herbs, help to expel toxins externally.

[0009] The properties, channels, effects, and modern pharmacological effects of each herb in this formula are as follows: Bupleurum: Properties and Channels Entered: Bitter, pungent, slightly cold. Enters the Liver and Gallbladder channels. Functions: Soothes the liver and relieves stagnation, regulates Qi, and is a fundamental medicine for treating breast lumps caused by liver Qi stagnation. Modern Pharmacological Actions: The saikosaponins it contains can inhibit the release of various inflammatory factors (such as TNF-α and IL-6), reducing inflammatory responses. It has a bidirectional regulatory effect on immune function, and can inhibit excessive immune responses in inflammatory states.

[0010] White peony root: Properties and channels: bitter, sour, slightly cold. Enters the liver and spleen channels. Functions: Nourishes blood and softens the liver, relieves spasms and pain. When combined with bupleurum, one disperses while the other astringes, assisting bupleurum in soothing the liver while preventing it from depleting yin and blood. Modern pharmacological effects: Total glycosides of white peony root are its core active ingredients, possessing significant anti-inflammatory and central and peripheral analgesic effects. It also has a regulatory effect on abnormal cellular and humoral immunity.

[0011] Dandelion: Properties and Channels Entered: Bitter, sweet, cold. Enters the Liver and Stomach channels. Functions: Clears heat and detoxifies, reduces swelling and dissipates nodules, promotes urination and relieves strangury. A key medicine for treating carbuncles and boils caused by heat toxins, especially effective for mastitis. Modern Pharmacological Actions: Significantly inhibits common pathogens of mastitis such as Staphylococcus aureus and hemolytic streptococci. Reduces the level of inflammatory mediators by inhibiting pathways such as NF-κB. Scavenges free radicals and reduces oxidative damage to tissues. Enhances the phagocytic capacity of macrophages and strengthens non-specific immunity.

[0012] Forsythia: Properties and Channels Entered: Bitter, slightly cold. Enters the Lung, Heart, and Small Intestine channels. Functions: Clears heat and detoxifies, reduces swelling and dissipates nodules, disperses wind-heat. Synergistically enhanced with dandelion, it strengthens the body's ability to clear heat and toxins and dissipate swelling. Modern Pharmacological Effects: Inhibits various Gram-positive and Gram-negative bacteria and viruses. Forsythosides and other components significantly inhibit inflammatory responses and lower body temperature. It reduces capillary permeability, decreases inflammatory exudation, and promotes abscess absorption.

[0013] Cat's Claw Herb: Properties and Channels Entered: Sweet, pungent, warm. Enters the Liver and Lung channels. Functions: Resolves phlegm and dissipates nodules, detoxifies and reduces swelling. Specifically targets scrofula and nodules caused by phlegm-fire stagnation, targeting the "phlegm nodule" characteristic of serous cysts. Modern Pharmacological Effects: Traditionally used for lymph node tuberculosis, it has unique efficacy against chronic granulomatous inflammation (such as serous cysts). It can enhance the body's cellular immune function. It has an inhibitory effect on certain tumor cells and abnormally proliferating tissues, and may help inhibit ductal epithelial hyperplasia. It has a certain inhibitory effect on various bacteria.

[0014] Trichosanthes kirilowii: Properties and Channels Entered: Sweet, slightly bitter, cold. Enters the Lung, Stomach, and Large Intestine channels. Functions: Clears heat and resolves phlegm, relieves chest congestion and dissipates nodules, moistens dryness and lubricates the intestines. It is a key medicine for resolving phlegm and dissipating nodules, specifically targeting the pathogenesis of phlegm-heat accumulation in breast lumps. Modern Pharmacological Effects: The amino acids it contains have expectorant effects. Trichosanthes kirilowii peel extract can dilate coronary arteries and improve microcirculation; this effect may be beneficial in improving local tissue blood supply. Trichosanthes kirilowii seeds have a laxative effect, consistent with the traditional Chinese medicine principle of the lung and large intestine being internally and externally related, and addressing the root cause.

[0015] Pinellia ternata (processed): Properties and Channels: Pungent, warm; toxic. Enters the spleen, stomach, and lung channels. Functions: Dries dampness and resolves phlegm, relieves nausea and vomiting, disperses nodules and reduces swelling. When combined with Trichosanthes kirilowii, it enhances the phlegm-resolving and nodule-dispersing effects. Modern pharmacological effects: Inhibits the vomiting and coughing centers. Has inhibitory effects on various experimental inflammations. Inhibits certain cancer cells and their abnormal proliferation.

[0016] White mustard seed: Properties and channels: pungent, warm. Enters the lung channel. Functions: warms the lungs, resolves phlegm, promotes qi circulation, disperses nodules, unblocks channels, and relieves pain. Especially effective in removing phlegm from the skin and membranes, reaching directly to the interstitial tissue of the breast, making it a key drug for dispersing phlegm nodules and carbuncles. Modern pharmacological effects: Glucosinolates, after hydrolysis, produce irritating substances that can cause skin congestion. When taken internally, they can stimulate the respiratory mucosa and promote expectoration. In formulas, it may play a role in "warming and dispersing," promoting local blood circulation, and facilitating the dissipation of phlegm and blood stasis.

[0017] Dried tangerine peel: Properties and channels: pungent, bitter, warm. Enters the spleen and lung channels. Functions: Regulates qi and strengthens the spleen, dries dampness and resolves phlegm. When qi flows smoothly, phlegm dissipates; when the spleen is strengthened, phlegm has no reason to arise. This is a representative principle of treating phlegm by first regulating qi. Modern pharmacological effects: Promotes the secretion of digestive juices and eliminates intestinal gas. Its volatile oil has a stimulating expectorant effect.

[0018] Poria cocos: Properties and Channels Entered: Sweet, bland, neutral. Enters the Heart, Lung, Spleen, and Kidney channels. Functions: Promotes diuresis and eliminates dampness, strengthens the spleen and calms the mind. Strengthening the spleen prevents the generation of phlegm, and eliminating dampness helps phlegm to descend. Modern Pharmacological Effects: Has a definite diuretic effect. Poria cocos polysaccharides can enhance the body's immune function.

[0019] Danshen (Salvia miltiorrhiza): Properties and Channels Entered: Bitter, slightly cold. Enters the Heart and Liver channels. Functions: Activates blood circulation and removes blood stasis, cools the blood and reduces swelling. Targeting the blood stasis pathogenesis of lumps, it is a key herb for activating blood circulation and removing blood stasis, and can also clear heat from blood stasis. Modern Pharmacological Effects: Dilates blood vessels, reduces blood viscosity, and inhibits platelet aggregation. Components such as salvianolic acid have strong antioxidant and anti-inflammatory effects. Promotes fibrinolysis, which is beneficial for softening and absorbing proliferating tissues.

[0020] Moutan bark: Properties and channels: Bitter, pungent, slightly cold. Enters the heart, liver, and kidney channels. Functions: Clears heat and cools the blood, invigorates blood circulation and removes blood stasis. Clears latent heat in the blood and disperses stagnant blood. Modern pharmacological effects: Paeonol is its main active ingredient, exhibiting significant anti-inflammatory and anti-allergic effects.

[0021] Red peony root: Properties and channels: Bitter, slightly cold. Enters the liver channel. Functions: Clears heat and cools the blood, disperses blood stasis and relieves pain. Synergistically, it enhances the effects of cooling the blood, promoting blood circulation, dispersing blood stasis, and relieving pain when combined with danshen and moupi. Modern pharmacological effects: Significantly antiplatelet aggregation and antithrombotic effects, improves blood rheology. Total glycosides of red peony root have clear anti-inflammatory activity. It has an antispasmodic effect on smooth muscle.

[0022] Gleditsia sinensis thorns: Properties and channels: pungent, warm. Enters the liver and stomach channels. Functions: reduces swelling and promotes pus drainage, eliminates toxins, and kills parasites. Its sharp properties allow it to directly reach the affected area, penetrating and rupturing hardened tissues to promote their dissipation or rupture, effectively addressing the stage where pus is about to pus but has not yet formed, embodying the principle of promoting pus drainage. Modern pharmacological effects: significantly inhibits acute and chronic inflammation. Can enhance the body's immunity. Inhibits cell proliferation, which may help inhibit granuloma formation.

[0023] Deer antler glue: Properties and channels: sweet, salty, warm. Enters the liver and kidney channels. Functions: Warms and tonifies the liver and kidneys, nourishes essence and blood, stops bleeding, and promotes tissue regeneration. It is a classic formula for treating yin-type carbuncles, used in combination with other warming and invigorating herbs to replenish essence and blood and help the body's resistance to expel toxins and prevent the accumulation of pathogenic factors. Modern pharmacological effects: Rich in amino acids and polypeptides, it can enhance cellular and humoral immune function and improve disease resistance. It supplements nutrition and promotes the production of red blood cells and hemoglobin. It may help repair chronically inflamed tissues.

[0024] As a further explanation of the present invention, the composition is made from the following medicinal materials in parts by weight: 12 parts Bupleurum chinense, 15 parts Paeonia lactiflora, 25 parts Taraxacum mongolicum, 12 parts Forsythia suspensa, 15 parts Uncaria rhynchophylla, 18 parts Trichosanthes kirilowii, 9 parts Pinellia ternata, 9 parts Sinapis alba, 9 parts Citrus reticulata peel, 15 parts Poria cocos, 15 parts Salvia miltiorrhiza, 10 parts Paeonia suffruticosa, 12 parts Paeonia lactiflora, 9 parts Gleditsia sinensis thorns, and 9 parts Cervi cornu colla.

[0025] A second aspect of the present invention provides a pharmaceutical preparation for treating plasma cell mastitis, said preparation being made from the composition and excipients described in any one of the above-described embodiments.

[0026] A third aspect of this invention provides a traditional Chinese medicine phospholipid complex nanoparticle for treating plasma cell mastitis. The nanoparticle is obtained by nanoemulsification of a fluid extract prepared from the composition described in any one of the above-mentioned methods with phospholipids. This invention improves the drug component into a novel delivery system—phospholipid complex nanoparticles—by adding specific excipients. The phospholipids form a complex with the drug component, which is then prepared into nanoparticles, thereby improving the absorption and targeting of lipid-soluble components, thus exhibiting superior efficacy compared to traditional dosage forms such as decoctions, capsules, and pills.

[0027] The preparation method of the above-mentioned traditional Chinese medicine phospholipid complex nanoparticles for treating plasma cell mastitis includes the following steps: (1) Prepare a Chinese herbal water-extracted and alcohol-precipitated fluid extract from the composition described in any one of the above, and divide it into two portions, which are respectively referred to as the first fluid extract and the second fluid extract.

[0028] Specifically, the herbal water-extracted and alcohol-precipitated fluid extract described in step (1) above is prepared through the following steps: (11) The medicinal materials other than deer antler glue in the composition of any one of claims 1-2 are decocted and extracted, the filtrates are combined and concentrated to obtain a concentrated solution.

[0029] (12) Add ethanol to the concentrate for alcohol precipitation, take the supernatant to recover the ethanol, and obtain the fluid extract.

[0030] (13) After melting the deer antler glue, combine it with the fluid extract obtained in step (12) to obtain the Chinese herbal water-extracted alcohol-precipitated fluid extract.

[0031] (2) Extract the fat-soluble components of the first fluid extract to obtain a fat-soluble extract; react the fat-soluble extract with phospholipids in an organic solvent to prepare a phospholipid complex.

[0032] The extraction process of the fat-soluble components in step (2) above is as follows: add the extraction solvent to the first fluid extract, extract by ultrasonication, centrifuge to obtain the organic phase, repeat the extraction, combine the organic phases and recover the solvent under reduced pressure to obtain the fat-soluble extract; wherein, the extraction solvent is any one of chloroform-methanol mixed solvent, ethyl acetate, and methyl tert-butyl ether, preferably chloroform-methanol mixed solvent.

[0033] Furthermore, the phospholipid mentioned in step (2) is any one of soybean phospholipid, lecithin, and phosphatidylcholine, preferably soybean phospholipid; the mass ratio of the phospholipid to the fat-soluble extract is (1-5):1; the organic solvent is any one of anhydrous ethanol, methanol, and acetone, preferably anhydrous ethanol; the reaction conditions are: stirring in a water bath at 30-60℃ for 2-4 hours.

[0034] Soybean phospholipids, as the main membrane material, form phospholipid complexes with hydrophobic active ingredients in the formula (such as tanshinone, saikosaponin, taraxasterol, etc.), which can improve the dispersibility of these ingredients in water and their intestinal absorption.

[0035] (3) The phospholipid complex and surfactant are dissolved in the organic phase, and the second fluid extract is used as the aqueous phase. After mixing, the mixture is emulsified and homogenized to form a nanoemulsion.

[0036] The surfactant in step (3) is any one of poloxamer 188, Tween 80, Span 80, polyethylene glycol-15-hydroxystearate, and sodium cholate, preferably poloxamer 188; the organic phase is any one of chloroform, dichloromethane, ethyl acetate, and methyl tert-butyl ether, preferably chloroform; the emulsification is carried out by high-speed shear emulsification for 3-10 minutes; the homogenization is carried out by high-pressure homogenization at a pressure of 40-60 MPa for 3-7 cycles.

[0037] The surfactant in step (3), especially poloxamer 188, can prevent the aggregation of nanoparticles and may further increase the retention of the drug at the site of inflammation by inhibiting the efflux of P-glycoprotein.

[0038] (4) The nanoemulsion is freeze-dried to obtain the traditional Chinese medicine phospholipid complex nanoparticles.

[0039] The fourth aspect of the present invention provides the use of the above-described pharmaceutical composition, or the above-described traditional Chinese medicine phospholipid complex nanoparticles, or the traditional Chinese medicine phospholipid complex nanoparticles prepared by the above-described preparation method, in the preparation of a medicament for treating plasma cell mastitis.

[0040] Compared with the prior art, the present invention has the following beneficial technical effects: The traditional Chinese medicine compound provided by this invention is more in line with the complex pathogenesis of plasma cell mastitis in the mass stage and early development stage. Based on soothing the liver, it strengthens the clearing heat and detoxifying to suppress heat toxins, and introduces the elimination of toxins and carbuncles for early intervention to prevent abscess formation. This allows the prescription to play a role in the mass stage of plasma cell mastitis while effectively preventing the mass from evolving further into the abscess stage.

[0041] The traditional Chinese medicine phospholipid complex nanoparticles provided by this invention improve the drug components into a novel delivery system—phospholipid complex nanoparticles—by adding specific excipients. The phospholipids form a complex with the drug components and are then prepared into nanoparticles, thereby improving the absorption and targeting of lipid-soluble components, thus exhibiting better efficacy than traditional dosage forms such as ordinary traditional Chinese medicine decoctions, capsules, and pills.

[0042] Animal experiments show that the drugs provided by this invention can inhibit the growth of inflammatory breast masses and exert anti-inflammatory effects. Furthermore, the complex nanoparticles provided by this invention are more effective than ordinary freeze-dried Chinese medicine powders. The absence of any pair of Chinese medicine ingredients in the compound formula provided by this invention leads to a decrease in overall efficacy, thus demonstrating the synergistic effect of the components in the compound formula. Attached Figure Description

[0043] Figure 1 The results of H&E staining of some mouse mammary tissues are shown. Figure 1 (a)-(e) show the staining results of the normal group, model group, positive control group, Example 1 group, and Example 2 group, respectively.

[0044] Figure 2 The results of mammary tumor volume measurement in each group of mice are shown in the figure. The significance level marked δ indicates that the difference between the two groups is P<0.01. The expression indicates that P < 0.01 compared to the model group; # indicates that P < 0.05 compared to Example 1 group; ## indicates that P < 0.01 compared to Example 1 group; n = 8.

[0045] Figure 3 The results of pro-inflammatory factor concentration detection in mammary tissue of mice in each group are shown in the figure. The significance mark δδ indicates that the difference between the two groups is P<0.01. The expression indicates that the p-value is less than 0.01 compared to the model group; # indicates that the p-value is less than 0.05 compared to Example 1 group; ## indicates that the p-value is less than 0.01 compared to Example 1 group; n=8.

[0046] Figure 4 The results of CD138-positive plasma cells in mammary tissue of mice in each group are shown in the figure. The significance level marked δδ indicates that the difference between the two groups is P<0.01. The expression indicates that the p-value is less than 0.01 compared to the model group; # indicates that the p-value is less than 0.05 compared to Example 1 group; ## indicates that the p-value is less than 0.01 compared to Example 1 group; n=8. Detailed Implementation

[0047] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0048] Example 1 This embodiment provides a freeze-dried powder of traditional Chinese medicine for treating plasma cell mastitis, and its specific preparation process is as follows: S1. Processing of medicinal materials: Weigh each medicinal material precisely according to the following proportions: Bupleurum chinense 12g, Paeonia lactiflora 15g, Taraxacum mongolicum 25g, Forsythia suspensa 12g, Uncaria rhynchophylla 15g, Trichosanthes kirilowii 18g, Pinellia ternata 9g, Sinapis alba 9g, Citrus reticulata 9g, Poria cocos 15g, Salvia miltiorrhiza 15g, Paeonia suffruticosa 10g, Paeonia lactiflora 12g, and Gleditsia sinensis 9g. Then grind each medicinal material into a coarse powder of 20-40 mesh for later use.

[0049] S2. Decoction and extraction: Add 10 times the amount of water to the crude Chinese medicine powder obtained in S1, soak for 30 minutes, boil and keep simmering for 1.5 hours, filter to obtain the first filtrate, add 8 times the amount of water to the remaining residue, boil and keep simmering for 1 hour, filter to obtain the second filtrate, combine the two filtrates to obtain the Chinese medicine extract.

[0050] S3. Alcohol precipitation: Concentrate the Chinese herbal extract to a relative density of 1.10-1.15 (60℃), add 95% ethanol to make the alcohol content reach 60%, let stand for 24 hours, filter, take the supernatant, and recover the ethanol until there is no alcohol taste to obtain the Chinese herbal fluid extract.

[0051] S4. Deer antler glue treatment: Add 9g of deer antler glue to 30ml of warm water and melt it at 55℃. Filter to remove insoluble matter and combine it with the fluid extract obtained in S3.

[0052] S5. Freeze-drying: The herbal extract obtained in S4 is pre-frozen at -40℃ for 2 hours, then kept at -20℃ for 10 hours, and finally heated to 25℃ and kept for 10 hours for freeze-drying to obtain freeze-dried herbal powder.

[0053] Example 2 This embodiment provides a traditional Chinese medicine phospholipid complex nanoparticle for treating plasma cell mastitis, and its specific preparation process is as follows: S1. Processing of medicinal materials: Weigh each medicinal material precisely according to the following proportions: Bupleurum chinense 12g, Paeonia lactiflora 15g, Taraxacum mongolicum 25g, Forsythia suspensa 12g, Uncaria rhynchophylla 15g, Trichosanthes kirilowii 18g, Pinellia ternata 9g, Sinapis alba 9g, Citrus reticulata 9g, Poria cocos 15g, Salvia miltiorrhiza 15g, Paeonia suffruticosa 10g, Paeonia lactiflora 12g, and Gleditsia sinensis 9g. Then grind each medicinal material into a coarse powder of 20-40 mesh for later use.

[0054] S2. Decoction and extraction: Add 10 times the amount of water to the crude Chinese medicine powder obtained in S1, soak for 30 minutes, boil and keep simmering for 1.5 hours, filter to obtain the first filtrate, add 8 times the amount of water to the remaining residue, boil and keep simmering for 1 hour, filter to obtain the second filtrate, combine the two filtrates to obtain the Chinese medicine extract.

[0055] S3. Alcohol precipitation: Concentrate the Chinese herbal extract to a relative density of 1.10-1.15 (60℃), add 95% ethanol to make the alcohol content reach 60%, let stand for 24 hours, filter, take the supernatant, and recover the ethanol until there is no alcohol taste to obtain the Chinese herbal fluid extract.

[0056] S4. Deer antler glue treatment: Add 9g of deer antler glue to 30ml of warm water and melt it at 55℃. Filter to remove insoluble matter and combine it with the fluid extract obtained in S3.

[0057] S5. Extraction of lipid-soluble components: Take 1 / 2 of the fluid extract of traditional Chinese medicine obtained in S4 and add 3 times the volume of chloroform-methanol mixed solvent (2:1, v / v), sonicate for 30 minutes, centrifuge to obtain the organic phase; repeat the extraction twice, combine the organic phases, and then recover the solvent under reduced pressure at 40℃ to obtain the lipid-soluble extract.

[0058] S6. Formation of phospholipid complex: Weigh 1.5g of soybean phospholipid (with a weight ratio of approximately 3:1 to the fat-soluble extract), add it to the above fat-soluble extract, then add 20ml of anhydrous ethanol to dissolve it, stir and react for 3 hours under 50℃ water bath conditions, remove the ethanol under reduced pressure at 40℃ to obtain the phospholipid complex.

[0059] S7. Preparation of nanoemulsion: Dissolve the phospholipid complex in 5 ml of chloroform, add 1880.3 g of poloxamer, dilute the remaining 1 / 2 of the herbal extract (water-soluble part) with distilled water to 50 ml, slowly add the organic phase dropwise to the aqueous phase, and emulsify by high-speed shearing (10000 rpm, 5 minutes) to obtain the pre-emulsion; transfer the pre-emulsion to a high-pressure homogenizer and cycle it 5 times under a pressure of 50 MPa to obtain the nanoemulsion.

[0060] S8. Freeze-drying: The nanoemulsion is pre-frozen at -40℃ for 2 hours, then kept at -20℃ for 10 hours, and finally heated to 25℃ and kept for 10 hours for freeze-drying to obtain composite nanoparticles.

[0061] Compare with Example 1 This comparative example provides a freeze-dried powder of traditional Chinese medicine for treating plasma cell mastitis. The specific preparation process is different from that of the freeze-dried powder of traditional Chinese medicine provided in Example 1, except that Bupleurum chinense and Paeonia lactiflora are omitted in step 1.

[0062] Compare with Example 2 This comparative example provides a freeze-dried Chinese medicine powder for treating plasma cell mastitis. The specific preparation process differs from that of the freeze-dried Chinese medicine powder provided in Example 1 only in that dandelion, forsythia, and cat's claw grass are omitted in step 1.

[0063] Compare with Example 3 This comparative example provides a freeze-dried Chinese medicine powder for treating plasma cell mastitis. The specific preparation process differs from that of the freeze-dried Chinese medicine powder provided in Example 1 only in that the three herbs, Trichosanthes kirilowii, Pinellia ternata, and Sinapis alba, are omitted in step 1.

[0064] Compare with Example 4 This comparative example provides a freeze-dried Chinese medicine powder for treating plasma cell mastitis. The specific preparation process differs from that of the freeze-dried Chinese medicine powder provided in Example 1 only in that the two herbs, tangerine peel and poria, are omitted in step 1.

[0065] Compare with Example 5 This comparative example provides a freeze-dried traditional Chinese medicine powder for treating plasma cell mastitis. The specific preparation process differs from that of the freeze-dried traditional Chinese medicine powder provided in Example 1 only in that the three herbs, Danshen, Mudanpi, and Chishao, are omitted in step 1.

[0066] Compare with Example 6 This comparative example provides a freeze-dried powder of traditional Chinese medicine for treating plasma cell mastitis. The specific preparation process is different from that of the freeze-dried powder of traditional Chinese medicine provided in Example 1, except that the soapberry thorn is omitted in step 1, and step 4 is also omitted, that is, the deer antler glue is omitted.

[0067] I. The therapeutic effect of the lyophilized powder provided in the embodiments and control examples of this invention on a mouse model of plasma cell mastitis was verified through animal experiments.

[0068] 1. Experimental materials: 1.1 Laboratory Animals Balb / c female mice aged 6–8 weeks and weighing 18–20 g were selected and purchased from the Experimental Animal Center of Xi'an Jiaotong University. All mice underwent one week of acclimatization rearing under standard laboratory conditions before the start of the formal experiments.

[0069] 1.2 Experimental reagents: Xiaoru Sanjie Capsules, Manufacturer: Shandong Buchang Shenzhou Pharmaceutical Co., Ltd.; Approval Number: National Medicine Approval Number Z20055636; Specification: 0.4g 90 pills.

[0070] The lyophilized powders prepared in the above examples and control examples.

[0071] Experimental methods 2.1 Animal model establishment, grouping, and drug administration Establishment of a mouse model of plasma cell mastitis: Normal human mammary tissue was collected and added to sterile physiological saline at a ratio of 1:3. The tissue was mechanically homogenized for 5 minutes at low temperature (3-4℃), followed by ultrasonic disruption and centrifugation to obtain the supernatant, which yielded a tissue antigen extract. The antigen extract was repeatedly mixed with an equal volume of complete Freund's adjuvant (CFA) at 4℃ for 20 minutes to form a stable emulsion. Mice were anesthetized, and 50 μL of the emulsion was subcutaneously injected into the right fourth pair of mammary glands. Observation was continued for 3 weeks until a chronic inflammatory mass formed at the injection site. One week after mass formation, 50 μL of a 1 μg / mL recombinant mouse IL-6 protein solution was subcutaneously injected around the mass. One week after IL-6 injection, the mouse model of plasma cell mastitis was established.

[0072] Grouping: Mice that successfully modeled the disease were randomly divided into 10 groups of 8 mice each: model group, positive control group, Example 1 group, Example 2 group, Control 1 group, Control 2 group, Control 3 group, Control 4 group, Control 5 group, and Control 6 group. Eight healthy mice were also used as normal controls.

[0073] Administration: After grouping, mice in each group were administered the drug via gavage for 28 consecutive days. Mice in Example 1 group received the lyophilized traditional Chinese medicine powder provided in Example 1 at a dose of 32 mg / kg / day. Mice in Example 2 group received the complex nanoparticles provided in Example 2 at a dose of 32 mg / kg / day. Mice in Control Examples 1 to 6 received the corresponding lyophilized traditional Chinese medicine powder provided in each control example at a dose of 32 mg / kg / day. Mice in the positive control group received Xiaoru Sanjie capsules at a dose of 100 mg / kg / day. Mice in the model group and normal group were administered the same volume of sterile saline via gavage as those in the Example and Control groups.

[0074] 2.2 Observation Indicators 2.2.1 Measurement of breast mass volume Twenty-eight days after drug administration, the longest diameter (a) and the shortest perpendicular diameter (b) of the mass in the fourth pair (groin) mammary gland region of mice were measured using vernier calipers. The mass volume (mm³) was calculated using the formula: V = (π / 6) a b², unit: mm³.

[0075] 2.2.2 Detection of pro-inflammatory factors in mammary tissue of mice in each group Twenty-eight days after administration, mice in each group were anesthetized by injection, and then breast tumor specimens were removed. Some of the breast tumor specimens were quick-frozen in liquid nitrogen, crushed, and weighed. PBS was added at a ratio of 1:7 (weight:volume), and then the mixture was shaken, centrifuged, and the supernatant was collected to obtain tissue homogenate. The concentrations of IL-6 and TNF-α in the homogenate were detected strictly according to the ELISA kit instructions.

[0076] 2.2.3 Histopathological observation Breast lumps were collected, and a portion of the breast tissue was cut, fixed with 10% formaldehyde, dehydrated, embedded, sectioned (5μm), dewaxed, stained with eosin-hematoxylin and eosin (H&E), cleared and mounted, and finally mounted with neutral resin. The pathological tissues of each group of mice were observed under a microscope.

[0077] 2.2.4 Calculation of the proportion of CD138-positive plasma cells in breast tissue Breast lumps were collected, and a portion of breast tissue was excised, fixed in 10% formaldehyde, dehydrated, embedded, sectioned (5μm), dewaxed, and antigen-retrieved before immunohistochemical staining: primary antibody (CD138 antibody, 1:500 dilution, incubated overnight at 4°C), secondary antibody (incubated at room temperature), DAB staining, hematoxylin counterstaining, differentiation, blue staining, and mounting. The tissue was then observed under a microscope, and the number of CD138-positive plasma cells and the total number of cells in the field of view were counted. The ratio was calculated using the following formula: CD138-positive plasma cell percentage (%) = (number of CD138-positive cells / total number of cells) × 100%.

[0078] Statistical analysis All data were statistically analyzed using SPSS 26.0 software. Quantitative data were normally distributed and expressed as mean ± standard deviation (x̄ ± s). Independent samples t-tests were used for comparisons between two groups, and chi-square tests were used for categorical data. P < 0.05 or P < 0.01 was considered statistically significant.

[0079] Experimental results 4.1 Measurement results of mammary tumor volume in each group of mice.

[0080] Figure 2 The results of mammary tumor volume measurement in each group of mice are as follows: Figure 2It can be seen that the tumor volume in the model group was significantly larger than that in the normal group, indicating that the plasma cell mastitis model was successfully constructed. The tumor volume in the positive control group and each drug administration group (Examples 1-2) was significantly smaller than that in the model group, indicating that all tested drugs had the effect of inhibiting the growth of inflammatory mastitis tumors. Among them, the tumor volume in the Example 2 group was the smallest and significantly smaller than that in the Example 1 group, which indicates that the complex nanoparticles provided in Example 2 were more effective than the ordinary Chinese medicine lyophilized powder provided in Example 1. The tumor volume in all control groups (1-6) was larger than that in the Example 1 group, and the difference was statistically significant (P<0.05). This indicates that the efficacy of the drug formulations in the control groups was not as good as the complete formulation in Example 1. That is, the absence of any pair of Chinese medicines in the Chinese medicine compound provided by this invention will lead to a decrease in the overall efficacy. This further illustrates the importance of the principle of monarch, minister, assistant, and guide in the Chinese medicine compound of this invention. Only a complete combination of drugs can give full play to the synergistic effect between the components.

[0081] 4.2 Observation results of some mouse tissue pathology.

[0082] Figure 1 The results of H&E staining of some mouse mammary tissues are shown. Figure 1 (a)-(e) show the staining results of the normal group, model group, positive control group, Example 1 group, and Example 2 group, respectively. The figures show that the normal group had a basically normal breast tissue structure, regular alveolar morphology, and no inflammatory cell infiltration. The model group showed damaged breast tissue structure and extensive inflammatory cell infiltration. The positive control group, Example 1 group, and Example 2 group all showed reduced inflammatory cell infiltration compared to the model group, and varying degrees of tissue repair were observed, with Example 2 group showing the best degree of breast tissue repair.

[0083] 4.3 Results of detection of pro-inflammatory factors and CD138-positive plasma cells in mammary tissue of mice in each group.

[0084] Figure 3 , Figure 4The figures show the concentrations of pro-inflammatory factors and the detection results of CD138-positive plasma cells in the mammary tissue of mice in each group. As can be seen from the results, compared with the normal group, the model group showed significantly higher levels of IL-6 and TNF-α, as well as a significantly higher proportion of CD138-positive plasma cells (P<0.01), indicating that the plasma cell mastitis model was successfully established, the mammary tissue was in an inflammatory state, and the body's immune response was activated. The positive control group and the groups in Examples 1-2 showed significantly lower levels of IL-6 and TNF-α, and a significantly lower proportion of CD138-positive plasma cells than the model group, indicating that all tested drugs had certain anti-inflammatory effects and could inhibit the release of inflammatory factors and the infiltration of plasma cells. Among them, the group in Example 2 had the lowest levels of IL-6 and TNF-α, and a significantly lower proportion of CD138-positive plasma cells than the group in Example 1 (P<0.05), indicating that the complex nanoparticles provided in Example 2 had a more significant anti-inflammatory effect than the ordinary traditional Chinese medicine freeze-dried powder provided in Example 1. The levels of IL-6 and TNF-α, and the proportion of CD138-positive plasma cells in all control groups (1-6) were higher than those in Example 1, and the differences were statistically significant (P<0.05 or P<0.01). This indicates that the efficacy of the drug formulations in the control groups was inferior to that of the complete formulation in Example 1. In other words, the absence of any pair of herbs in the traditional Chinese medicine compound provided by this invention leads to a decrease in overall anti-inflammatory efficacy. This further illustrates the importance of the principle of monarch-minister-adjuvant-guide compatibility in the traditional Chinese medicine compound of this invention; only a complete drug combination can fully exert the synergistic effect between the components.

[0085] The animal experimental results show that, compared with the normal group, the model group exhibited significantly larger breast mass volume, significantly increased levels of IL-6 and TNF-α, and a significantly higher proportion of CD138-positive plasma cells. Breast tissue structure was disrupted with extensive inflammatory cell infiltration, indicating the successful establishment of the plasma cell mastitis model. The positive control group and each drug-treated group (Examples 1-2) showed significantly smaller mass volume, inflammatory factor levels, and plasma cell proportions than the model group, reduced inflammatory cell infiltration, and varying degrees of tissue repair, demonstrating that all tested drugs could inhibit the growth of inflammatory breast masses and exert anti-inflammatory effects. Specifically, the Example 2 group showed the smallest mass volume, inflammatory factor levels, and plasma cell proportions, significantly smaller than the Example 1 group, indicating that the complex nanoparticles are more effective than ordinary freeze-dried Chinese medicine powder. All control groups showed higher values ​​than the Example 1 group, indicating that the absence of any pair of Chinese medicine ingredients in the compound formula would lead to a decrease in overall efficacy, thus confirming the synergistic effect of the components in the Chinese medicine compound formula provided by this invention.

[0086] Clinical trials have verified the therapeutic effect of the pharmaceutical composition provided by this invention on plasma cell mastitis in the mass stage.

[0087] Clinical data General Information Collect data on patients who visited the First Affiliated Hospital of Xi'an Jiaotong University School of Medicine between January 2025 and October 2025. Patients diagnosed with plasma cell mastitis in the mass stage at the outpatient department of the affiliated hospital were selected. 100 patients who met the following criteria were randomly divided into a treatment group and a control group, with 50 patients in each group. There was no statistically significant difference in age between the two groups (P>0.05).

[0088] 1.2 Diagnostic criteria 1.2.1 Western Medicine Diagnostic Criteria The following diagnostic criteria were established with reference to the 2016 Expert Consensus on the Diagnosis and Treatment of Non-Lactational Mastitis: Clinical manifestations: Main symptoms: Painless or painful lumps in one or both breasts, the lumps are hard or tough, with indistinct borders and poor mobility, accompanied by nipple retraction and nipple discharge (mostly serous, bloody, or purulent). Some patients may experience local skin redness and swelling, and elevated skin temperature, but systemic symptoms of infection or poisoning such as fever are usually not obvious.

[0089] Auxiliary examinations: Breast ultrasound findings include dilated mammary ducts, periductal hypoechoic areas, and mixed or hypoechoic masses with indistinct borders, heterogeneous internal echoes, and may be accompanied by liquefaction.

[0090] Pathological diagnosis: Core needle biopsy pathological examination revealed: dilation of mammary ducts, infiltration of a large number of plasma cells and lymphocytes around the ducts, with or without fibrous tissue hyperplasia and fat necrosis.

[0091] 1.2.2 Traditional Chinese Medicine Diagnostic Criteria The following diagnostic criteria were developed in accordance with the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines" and industry consensus: Syndrome: Liver Qi stagnation, phlegm and blood stasis, and internal accumulation of heat toxin.

[0092] Main symptoms: ① Breast lumps, swelling, or stabbing pain. ② The lumps are hard or tough, immovable, or accompanied by tenderness.

[0093] Secondary symptoms: ① Depression, irritability, chest tightness and rib distension. ② Bitter taste in the mouth, dry mouth. ③ Slight redness or unchanged skin color in the affected area, with increased skin temperature. ④ Nipple discharge (serous or bloody).

[0094] Tongue and pulse: ① Tongue body: dark red or purplish-dark, or with petechiae or ecchymosis. ② Tongue coating: thin yellow or yellow and greasy.

[0095] ③ Pulse characteristics: wiry, wiry-slippery, or hesitant.

[0096] Diagnostic requirements: All primary symptoms must be present, along with at least two secondary symptoms. A diagnosis can be made by combining the patient's tongue and pulse examination.

[0097] 1.3 Inclusion Criteria Subjects who meet all of the following criteria are eligible for inclusion: ① Women aged 20 to 50 who are not breastfeeding or pregnant.

[0098] ② Meeting the main clinical manifestations and breast ultrasound findings in the above-mentioned Western medicine diagnostic criteria, and confirmed by puncture pathology as plasma cell mastitis in the mass stage.

[0099] ③ Meets the above-mentioned TCM diagnostic criteria (liver qi stagnation, phlegm and blood stasis, and internal heat toxin).

[0100] ④ Plasma cell mastitis in the mass stage, where the surface has not ruptured and no sinus tract or fistula has formed.

[0101] ⑤ Participate in this study voluntarily and sign a written informed consent form.

[0102] 1.4 Exclusion Criteria ① Women under 20 years of age or over 50 years of age, or who are pregnant or breastfeeding.

[0103] ② Meets the diagnostic criteria for PCM, but has any of the following conditions: a mature abscess has formed (obvious liquefactive necrotic area visible on ultrasound, diameter ≥1.5cm); the mass is accompanied by skin ulceration or fistula formation; clinical and auxiliary examinations suggest the presence of other diseases such as fibroadenoma, hamartoma, or breast cancer.

[0104] ③ Patients with serious primary diseases of the heart, liver, kidneys, hematopoietic system, etc., or mental illness.

[0105] ④ Patients who have used antibiotics, glucocorticoids, nonsteroidal anti-inflammatory drugs, or other medications (including traditional Chinese medicine) for this disease within one month prior to enrollment.

[0106] ⑤ Individuals allergic to any known component of the study drug (any one of the Chinese herbs in the compound) or the control drug (Xiaoru Sanjie Capsules).

[0107] ⑥ Those who are currently participating in other drug clinical trials or who have participated in other clinical trials within 3 months prior to enrollment.

[0108] 1.5 Shedding / Rejection Criteria ① Regardless of the reason, the subject voluntarily requested to withdraw from the trial.

[0109] ② If a serious adverse event (SAE) or intolerable adverse reaction occurs, and it is determined that the patient is no longer suitable to continue receiving the investigational drug.

[0110] ③ Failure to use medication as prescribed, unauthorized use of prohibited combined medications, and impact on efficacy and safety evaluation.

[0111] Research Methods 2.1 Research Subjects One hundred patients who met the diagnostic criteria in section 1.2 above were selected from those diagnosed with plasma cell mastitis in the mass stage at the outpatient department of the First Affiliated Hospital of Xi'an Jiaotong University School of Medicine. These 100 patients were randomly divided into a treatment group and a control group, with 50 patients in each group.

[0112] 2.2 Treatment methods Control group: Oral administration of Xiaoru Sanjie Capsules (Manufacturer: Shandong Buchang Shenzhou Pharmaceutical Co., Ltd.; Approval Number: National Medicine Approval Number Z20055636; Specification: 0.4g) 90 pills), 3 pills (1.2g) each time, 3 times a day, after meals; 4 weeks is one course of treatment, and 2 consecutive courses of treatment (8 weeks in total).

[0113] Treatment group: Patients received an oral decoction prepared from a self-formulated traditional Chinese medicine compound (Bupleurum chinense 12g, Paeonia lactiflora 15g, Taraxacum mongolicum 25g, Forsythia suspensa 12g, Uncaria rhynchophylla 15g, Trichosanthes kirilowii 18g, Pinellia ternata 9g, Sinapis alba 9g, Citrus reticulata 9g, Poria cocos 15g, Salvia miltiorrhiza 15g, Paeonia suffruticosa 10g, Paeonia lactiflora 12g, Gleditsia sinensis 9g). The decoction was prepared by the pharmacy of the First Affiliated Hospital of Xi'an Jiaotong University, with each packet containing 250mL. One dose was taken twice daily, morning and evening, half an hour after meals. One course of treatment lasted four weeks, with two consecutive courses (a total of eight weeks).

[0114] 2.3 Observation Content Based on the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines (Trial)" (2022 Edition) and considering the characteristics of this disease, a quantitative scoring table was developed. Evaluations were conducted before treatment and at the end of the 8th week of treatment (at the end of treatment).

[0115] Table 1. Detailed Table of Clinical Symptom Scores

[0116] In this project, breast pain was assessed using the Visual Analogue Scale (VAS): 0 points for no pain, 1-3 points for mild pain, 4-6 points for moderate pain, and 7-10 points for severe pain. Lump size was measured using high-frequency breast ultrasound, measuring the long axis (L) and short axis (S) of the lump, and calculated as lump size (cm²) = [L(cm) × S(cm)]. Other assessments, including lump hardness, skin color and temperature, discharge, and tongue and pulse characteristics, were performed through specialist palpation and visual inspection.

[0117] 2.4 Efficacy Evaluation Criteria The efficacy evaluation criteria refer to the nimodiflucan method, and the efficacy index (n) is calculated as: [(pre-treatment score - post-treatment score) / pre-treatment score] × 100%. Cure: Therapeutic efficacy index (n) ≥ 90%.

[0118] Significant efficacy: 70% ≤ efficacy index (n) < 90%.

[0119] Effective: 30% ≤ efficacy index (n) < 70%.

[0120] Ineffective: efficacy index (n) n < 30%, or disease progression.

[0121] Overall effective rate (%) = (number of cured + significantly effective + effective cases) / total number of cases × 100%.

[0122] 3. Statistical methods All data were statistically analyzed using SPSS 26.0 software. Quantitative data were normally distributed and expressed as mean ± standard deviation (x̄ ± s). Independent samples t-tests were used for comparisons between two groups, and chi-square tests were used for categorical data. P < 0.05 or P < 0.01 was considered statistically significant.

[0123] 4. Test Results Of the 100 patients with plasma cell mastitis in the mass stage included in this study, one patient in the control group was lost to follow-up due to a job transfer, and one patient in the treatment group dropped out due to mild gastrointestinal discomfort. A total of 98 patients completed the entire treatment course and were included in the efficacy analysis, including 49 in the treatment group and 49 in the control group.

[0124] 4.1 Comparison of total clinical symptom scores between the two groups of patients Table 2 Comparison of total clinical symptom scores before and after treatment in the two groups of patients.

[0125] Significance markers in the table The value is P<0.01 compared to before treatment, n=49.

[0126] As shown in Table 2, the total clinical symptom scores of both groups decreased significantly after treatment compared with those before treatment (P<0.01), indicating that both treatment regimens were effective. Further comparison between groups showed that the total score of the treatment group was significantly lower than that of the control group after treatment, and the difference was statistically significant (P<0.01).

[0127] 4.2 Comparison of clinical efficacy between the two groups of patients Table 3 Comparison of clinical efficacy between the two groups of patients

[0128] The significance marker * in the table indicates that P < 0.05 compared with the control group.

[0129] Based on the comparison of clinical efficacy between the two groups of patients, it can be seen that the total effective rate of the treatment group (95.92%) is significantly higher than that of the control group (81.63%). At the same time, the difference between the two groups is statistically significant, indicating that the self-formulated traditional Chinese medicine compound provided by this invention has shown significant efficacy in clinical trials.

[0130] It should be noted that, in this document, terms such as “comprising,” “including,” or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.

[0131] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A pharmaceutical composition for treating plasma cell mastitis, characterized in that, The composition is made from the following medicinal materials in parts by weight: Bupleurum chinense 10-15 parts, Paeonia lactiflora 10-20 parts, Taraxacum mongolicum 15-30 parts, Forsythia suspensa 10-15 parts, Uncaria rhynchophylla 10-20 parts, Trichosanthes kirilowii 15-25 parts, Pinellia ternata 6-12 parts, Sinapis alba 6-12 parts, Citrus reticulata 6-12 parts, Poria cocos 10-20 parts, Salvia miltiorrhiza 10-20 parts, Paeonia suffruticosa 5-15 parts, Paeonia lactiflora 10-15 parts, Gleditsia sinensis thorns 6-12 parts, and Cervi cornu colla 6-12 parts.

2. The pharmaceutical composition for treating plasma cell mastitis as described in claim 1, characterized in that, The composition is made from the following medicinal materials in parts by weight: Bupleurum 12 parts, White Peony Root 15 parts, Dandelion 25 parts, Forsythia 12 parts, Cat's Claw Herb 15 parts, Trichosanthes Fruit 18 parts, Prepared Pinellia 9 parts, White Mustard Seed 9 parts, Tangerine Peel 9 parts, Poria 15 parts, Salvia miltiorrhiza 15 parts, Moutan Bark 10 parts, Red Peony Root 12 parts, Gleditsia Sinensis Thorn 9 parts, and Deer Antler Glue 9 parts.

3. A pharmaceutical preparation for treating plasma cell mastitis, characterized in that, The formulation is made from the composition and excipients described in any one of claims 1-2.

4. A traditional Chinese medicine phospholipid complex nanoparticle for treating plasma cell mastitis, characterized in that, The nanoparticles are obtained by nanoemulsification of a fluid extract made from the composition of any one of claims 1-2 and a phospholipid.

5. A method for preparing traditional Chinese medicine phospholipid complex nanoparticles for treating plasma cell mastitis, characterized in that, Includes the following steps: (1) Prepare a traditional Chinese medicine water-extracted alcohol-precipitated fluid extract from the composition of any one of claims 1-2, and divide it into two portions, which are respectively referred to as the first fluid extract and the second fluid extract; (2) Extract the fat-soluble components of the first fluid extract to obtain a fat-soluble extract; react the fat-soluble extract with phospholipids in an organic solvent to prepare a phospholipid complex; (3) The phospholipid complex and surfactant are dissolved in the organic phase, and the second fluid extract is used as the aqueous phase. After mixing, the mixture is emulsified and homogenized to form a nanoemulsion. (4) The nanoemulsion is freeze-dried to obtain the traditional Chinese medicine phospholipid complex nanoparticles.

6. The preparation method according to claim 5, characterized in that, The herbal water-extracted alcohol-precipitated fluid extract described in step (1) is prepared through the following steps: (11) The medicinal materials other than deer antler glue in the composition of any one of claims 1-2 are decocted and extracted, the filtrates are combined and concentrated to obtain a concentrated solution; (12) Add ethanol to the concentrate for alcohol precipitation, take the supernatant to recover the ethanol, and obtain the fluid extract; (13) After melting the deer antler glue, combine it with the fluid extract obtained in step (12) to obtain the Chinese herbal water-extracted alcohol-precipitated fluid extract.

7. The preparation method according to claim 5, characterized in that, The extraction process of fat-soluble components in step (2) is specifically as follows: Add an extraction solvent to the first fluid extract, extract by ultrasonication, centrifuge to obtain the organic phase, repeat the extraction, combine the organic phases and recover the solvent under reduced pressure to obtain the lipid-soluble extract; wherein, the extraction solvent is any one of chloroform-methanol mixed solvent, ethyl acetate, and methyl tert-butyl ether.

8. The preparation method according to claim 5, characterized in that, The phospholipids mentioned in step (2) are any one of soybean phospholipids, lecithin, and phosphatidylcholine; the mass ratio of the phospholipids to the fat-soluble extract is (1-5):1; the organic solvent is any one of anhydrous ethanol, methanol, and acetone; the reaction conditions are: stirring in a water bath at 30-60℃ for 2-4 hours.

9. The preparation method according to claim 5, characterized in that, The surfactant mentioned in step (3) is any one of poloxamer 188, Tween 80, Span 80, polyethylene glycol-15-hydroxystearate, and sodium cholate; the organic phase is any one of chloroform, dichloromethane, ethyl acetate, and methyl tert-butyl ether; the emulsification is carried out by high-speed shear emulsification for 3-10 minutes; the homogenization is carried out by high-pressure homogenization at a pressure of 40-60 MPa for 3-7 cycles.

10. The use of the pharmaceutical composition of any one of claims 1-2, or the traditional Chinese medicine phospholipid complex nanoparticles of claim 4, or the traditional Chinese medicine phospholipid complex nanoparticles prepared by the preparation method of any one of claims 5-9, in the preparation of a medicament for treating plasma cell mastitis.

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