A traditional Chinese medicine composition for resisting heart aging, soft capsule preparation thereof and preparation method

Abstract

The application discloses a traditional Chinese medicine composition for resisting heart senility, a soft capsule preparation and a preparation method thereof, and belongs to the technical field of modernized traditional Chinese medicine preparations.The classical prescription Wuling Powder is scientifically combined with Guizhifuling Pill to form the traditional Chinese medicine composition which has the functions of warming yang, promoting water excretion, promoting blood circulation and removing blood stasis, and the traditional Chinese medicine composition is developed into a modernized soft capsule preparation by modern preparation technology.The application innovatively adopts a process in which the inclusion technology and the matrix compound are used to play a synergistic role, and a soft capsule with good stability is prepared.The application overcomes the defects of traditional decoction, such as inconvenience in carrying, unstable components and the like, significantly improves the retention rate of volatile components in the preparation and the stability of the preparation, ensures controllable product quality, and provides a more optimal modernized new traditional Chinese medicine dosage form for the prevention and treatment of heart senility.

Description

Technical Field

[0001] This invention belongs to the field of modern Chinese medicine preparation technology, specifically relating to a Chinese medicine composition for anti-cardiac aging, its soft capsule formulation, and preparation method. Background Technology

[0002] With the accelerating aging of the global population, cardiac aging and related diseases have become a significant chronic disease foundation threatening human health and lifespan. Currently, modern medicine lacks specific drugs for delaying cardiac aging, and clinical treatment mainly focuses on symptomatic intervention in end-stage conditions such as heart failure, failing to address the root causes of aging through early intervention and prevention. Traditional Chinese medicine theory considers "deficiency of heart and kidney yang, blood stasis and fluid retention" to be the core pathogenesis of cardiac aging. Wu Ling San combined with Gui Zhi Fu Ling Wan is an effective formula for treating cardiac aging caused by yang deficiency and fluid retention, and blood stasis and obstruction of the collaterals.

[0003] The combination of Wu Ling San and Gui Zhi Fu Ling Wan uses cinnamon twig as the principal ingredient, leveraging its warming and invigorating effects on the heart yang. Modern pharmacological studies have shown that the active ingredients in cinnamon twig, such as cinnamaldehyde and other volatile oils, can irritate the gastrointestinal mucosa. In clinical application, some patients, especially elderly patients with chronic heart disease (CHF) and spleen deficiency, have reported burning sensations, discomfort, or nausea in the epigastric region after taking this decoction. This "hidden" technical problem caused by the active ingredients themselves has never been mentioned or effectively resolved in existing technologies. It seriously affects patients' medication experience and long-term treatment adherence, hindering the clinical promotion and application of this excellent formula. Furthermore, the volatile components in cinnamon twig are easily lost and oxidized during the decoction's preparation and storage, leading to a decrease in the efficacy of the principal ingredient and affecting the stability and certainty of the therapeutic effect.

[0004] Therefore, there is an urgent need in this field for a modern Chinese medicine preparation that can overcome the inconvenience and unstable quality of traditional decoctions while retaining the efficacy of the original prescription, and can effectively reduce the gastrointestinal irritation of cinnamon twig volatile oil, improve medication safety and patient compliance. Summary of the Invention

[0005] The core objective of this invention is to simultaneously solve two key technical problems that have long existed but have not been given sufficient attention in existing decoction technology through a specific formulation process:

[0006] 1. A traditional Chinese medicine composition for anti-cardiac aging is provided. The composition is based on the combination of Wu Ling San and Gui Zhi Fu Ling Wan, and achieves the effect of delaying the aging process of the heart and improving cardiac function through the synergistic effect of "warming yang and promoting diuresis" and "activating blood circulation and removing blood stasis".

[0007] 2. Addressing the issue of low retention rate of volatile active ingredients. For easily dispersed volatile oil components (such as cinnamaldehyde) in the principal ingredient, cinnamon twig, an immediate encapsulation process after extraction is employed. This effectively protects these components during extraction, drying, and storage, significantly improving the retention rate and stability of the volatile oil in cinnamon twig, ensuring the controllability of the content of key active substances and the stability of the therapeutic effect.

[0008] 3. Addressing gastrointestinal irritation caused by active ingredients. By converting cinnamon twig volatile oil into a β-cyclodextrin inclusion complex, its release characteristics are altered, allowing the volatile oil to be released slowly in the stomach and further released and absorbed in the intestines, thereby significantly reducing its direct irritation to the gastric mucosa. This process effectively improves medication safety and patient compliance, and is especially suitable for elderly patients with weak spleen and stomach.

[0009] By achieving the above objectives, the traditional Chinese medicine composition of Wuling Powder and Guizhi Fuling Pill, and its soft capsule formulation provided by this invention, have advantages over traditional decoctions in terms of stable quality, definite efficacy, high safety, convenient portability, and good patient compliance. The traditional Chinese medicine formulation is preferably a soft capsule.

[0010] The prescription dosage of the Chinese herbal composition is as follows: 15-25 parts of cinnamon twig, 10-15 parts of polyporus umbellatus, 15-20 parts of poria cocos, 15-20 parts of alisma plantago-aquatica, 10-15 parts of atractylodes macrocephala, 10-15 parts of peony bark, 10-15 parts of peach kernel, and 10-15 parts of red peony root.

[0011] Preferably, the prescription dosage of the traditional Chinese medicine composition is as follows: 20 parts of cinnamon twig, 12 parts of polyporus umbellatus, 18 parts of poria cocos, 18 parts of alisma plantago-aquatica, 12 parts of atractylodes macrocephala, 12 parts of peony bark, 12 parts of peach kernel, and 12 parts of red peony root.

[0012] The traditional Chinese medicine soft capsule comprises the traditional Chinese medicine composition and excipients; the excipients comprise an inclusion compound and a matrix mixture;

[0013] Preferably, the inclusion compound is selected from one or more of hydroxypropyl-β-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, cellulose acetate phthalate, and polylactic acid-glycolic acid copolymer.

[0014] Preferably, the matrix mixture is selected from two or more of medium-chain triglycerides, corn oil, soybean oil, palm kernel oil, polyethylene glycol 600, glycerol, and propylene glycol.

[0015] Preferably, in the traditional Chinese medicine soft capsule, the inclusion compound is β-cyclodextrin, and the matrix mixture is medium-chain triglycerides and polyethylene glycol 600.

[0016] To achieve the above objectives, the present invention adopts the following technical solution:

[0017] Step (1): Extraction and inclusion of volatile oil from cinnamon twigs:

[0018] Take the prescribed amount of cinnamon twigs, crush them, place them in a volatile oil extractor, add 10 times the amount of water, and steam distill for 5 hours.

[0019] Collect the volatile oil and weigh it precisely in micrograms. Slowly add the volatile oil to a saturated aqueous solution of β-cyclodextrin (β-cyclodextrin:volatile oil = 4:1, w / w) with stirring, and stir at a constant temperature of 50°C for 2 hours.

[0020] After refrigerating and standing for 12 hours, filter the mixture and collect the precipitate (cinnamon twig volatile oil-β-cyclodextrin inclusion complex). Dry the precipitate at low temperature, grind it into a fine powder, and set it aside for later use.

[0021] Collect the distilled aromatic water and cinnamon twig residue for later use.

[0022] Step (2) Water extraction: Mix the cinnamon twig residue from step 1 with the remaining seven medicinal materials, add 8 times the amount of water, and extract dynamically for 1.5 hours, then filter; add 6 times the amount of water to the residue again, extract for 1 hour, and filter. Combine the two filtrates.

[0023] Step (3) Concentration: Combine the above aqueous extract with the aromatic water from step 1 and concentrate under reduced pressure (60℃, -0.08MPa) to a clear extract with a relative density of 1.12 (80℃).

[0024] Step (4) Content preparation: Take the clear extract, the cinnamon twig volatile oil inclusion complex obtained in step 1, and the matrix composed of medium chain triglycerides (MCT) and polyethylene glycol 600 (PEG600) (weight ratio 1:1), mix them in the ratio of clear extract: inclusion complex: matrix = 1:0.2:0.8, grind them evenly with a colloid mill to obtain a homogeneous content.

[0025] Step (5) Pelletizing and drying: In a clean environment, gelatin and glycerin are used as capsule material to compress the capsules. After shaping, they are cleaned and dried to obtain the soft capsules of traditional Chinese medicine of the present invention.

[0026] The traditional Chinese medicine composition and its soft capsules of the present invention can be used to prepare drugs for anti-cardiac aging.

[0027] The beneficial effects of this invention are as follows:

[0028] The combined formula exerts a synergistic effect: the components of Wuling Powder and Guizhi Fuling Pill work together to "warm the yang and promote diuresis" and "activate blood circulation and remove blood stasis", thus achieving the effect of delaying the aging process of the heart.

[0029] Dosage form innovation: For the first time, the combination of Wuling Powder and Guizhi Fuling Pill was developed into a soft capsule dosage form, which significantly improved the stability of the preparation and patient compliance.

[0030] Technological innovation: The "group extraction" process is adopted, first extracting the volatile oil of cinnamon twigs, and then extracting the residue with water, which maximizes the preservation of heat-sensitive volatile components in cinnamon twigs. This is something that cannot be achieved by the traditional decoction process, ensuring the efficacy of the principal drug. The "β-cyclodextrin inclusion complex of cinnamon twig volatile oil" effectively reduces the irritation of cinnamon twig volatile oil to the gastrointestinal tract.

[0031] Innovative matrix: The proprietary MCT / PEG composite matrix system ensures that the compound extract forms a stable, uniform, and non-stratified suspension system, overcoming the problem that conventional soft capsule matrices are not suitable for complex Chinese herbal extracts. Attached Figure Description

[0032] Figure 1 Flowchart of the preparation process of traditional Chinese medicine soft capsules in this invention;

[0033] Figure 2 : Represents the Doppler echocardiograms of mice in the positive control group, model control group, sample E (Wu Ling San) group, sample F (Gui Zhi Fu Ling Wan) group, and sample D (the combined formula of this invention);

[0034] Figure 3 The results of Masson staining of myocardial tissue from mice in the positive control group, model control group, sample E (Wu Ling San), sample F (Gui Zhi Fu Ling Wan), and sample D (the combined formula of this invention) are shown. Detailed Implementation

[0035] The embodiments of the present invention are described in detail below. The embodiments provided are exemplary and intended to explain the present invention, and should not be construed as limiting the scope of protection of the present invention.

[0036] The prescription of this invention is as follows: 20 parts of cinnamon twig, 12 parts of polyporus umbellatus, 18 parts of poria cocos, 18 parts of alisma plantago-aquatica, 12 parts of atractylodes macrocephala, 12 parts of peony bark, 12 parts of peach kernel, and 12 parts of red peony root.

[0037] β-Cyclodextrin was purchased from Shandong Binzhou Zhiyuan Biotechnology Co., Ltd.; medium-chain triglycerides (MCT) were purchased from Jiangsu Duoyang Bioengineering Technology Co., Ltd.; polyethylene glycol 600 (PEG600) was purchased from Shanghai Yihe Biotechnology Co., Ltd.; polyethylene glycol 400 (PEG400) was purchased from Xi'an Hongyao Pharmaceutical Excipients Co., Ltd.; the Masson trichrome staining kit (containing Weigert iron hematoxylin, Ponceau S, acid fuchsin solution, and aniline blue solution) was purchased from Beijing Bio-Lab Technology Co., Ltd. All other reagents, solvents, and other experimental materials were commercially available.

[0038] Example 1: Preparation of Traditional Chinese Medicine Soft Capsules

[0039] Step 1, Extraction and inclusion of volatile oil from cinnamon twig:

[0040] Take the prescribed amount of cinnamon twigs, crush them, place them in a volatile oil extractor, add 10 times the amount of water, and steam distill for 5 hours.

[0041] Collect the volatile oil and weigh it precisely in micrograms. Slowly add the volatile oil to a saturated aqueous solution of β-cyclodextrin (β-cyclodextrin:volatile oil = 4:1, w / w) with stirring, and stir at a constant temperature of 50°C for 2 hours.

[0042] After refrigerating and standing for 12 hours, filter the mixture and collect the precipitate (cinnamon twig volatile oil-β-cyclodextrin inclusion complex). Dry the precipitate at low temperature, grind it into a fine powder, and set it aside for later use.

[0043] Collect the distilled aromatic water and cinnamon twig residue for later use.

[0044] Step 2, Water Extraction: Mix the cinnamon twig residue from Step 1 with the remaining seven medicinal materials, add 8 times the amount of water, and extract dynamically for 1.5 hours, then filter. Add another 6 times the amount of water to the residue, extract for 1 hour, and filter. Combine the two filtrates.

[0045] Step 3, Concentration: Combine the above aqueous extract with the aromatic water from Step 1, and concentrate under reduced pressure (60℃, -0.08MPa) to obtain a clear extract with a relative density of 1.12 (80℃).

[0046] Step 4, Content Preparation: Take the clear extract, the cinnamon twig volatile oil inclusion complex obtained in Step 1, and the matrix composed of medium-chain triglycerides (MCT) and polyethylene glycol 600 (PEG600) (weight ratio 1:1), mix them in a ratio of clear extract: inclusion complex: matrix = 1:0.2:0.8, grind them evenly with a colloid mill to obtain a homogeneous content.

[0047] Step 5, pelleting and drying: In a clean environment, gelatin and glycerin are used as capsule material for pelleting. After shaping, the capsules are cleaned and dried to obtain the soft capsules of this invention.

[0048] Example 2: Selection of inclusion compounds

[0049] The preparation method of the traditional Chinese medicine soft capsules is the same as in Example 1, wherein the inclusion compounds are β-cyclodextrin, hydroxypropyl-β-cyclodextrin, γ-cyclodextrin, and cellulose acetate phthalate, respectively. The inclusion rate of the volatile oil inclusion complex of cinnamon twig was calculated, and the results are shown in Table 1 below.

[0050] Accurately weigh an appropriate amount (W_sample) of dried cinnamon twig volatile oil inclusion complex and place it in a Soxhlet extractor. Extract with n-hexane under continuous reflux until all volatile oil is extracted. Recover the n-hexane, and dry the residue under reduced pressure at 40°C to constant weight. Accurately weigh the residue; this is the weight of the unincluded free volatile oil (W_free). Calculate the inclusion rate using the following formula:

[0051]

[0052] in, This represents the total weight of the dried inclusion complex. ρ represents the volume of volatile oil from cinnamon twigs added, and ρ represents the density of the volatile oil from cinnamon twigs.

[0053]

[0054] Table 1. Inclusion rates of different volatile oil inclusion compounds of Cinnamomum cassia

[0055] β-cyclodextrin showed the best inclusion rate and oil loading capacity for cinnamon twig volatile oil, and its cavity size had the highest matching degree with the molecular group of cinnamon twig volatile oil.

[0056] Example 3 Selection of Matrix System

[0057] Except for the different content matrix, all samples used the same inclusion-treated extract and were prepared into soft capsules according to the same steps as in Example 1 of this invention. The samples were placed upright at room temperature, and the state of the contents was observed on days 0, 30, and 90. The presence of oil phase separation, precipitation, hardening, or capsule leakage was recorded. The results are shown in Table 2 below.

[0058] Table 2. Stability of traditional Chinese medicine soft capsules prepared with different matrix systems

[0059]

[0060] Conclusion: Neither single matrix nor common PEG400 / soybean oil combinations can maintain long-term stability. Among the complex extracts of this invention, only the MCT / PEG600 composite system of this invention exhibits excellent physical stability.

[0061] Example 4 Quality Stability Study

[0062] Three batches of soft capsules prepared in Example 1 (batch numbers: 20231001, 20231002, and 20231003) were subjected to accelerated testing under conditions of 40℃±2℃ and 75%±5% relative humidity, according to the General Chapter of Part IV of the 2020 edition of the Chinese Pharmacopoeia. Samples were taken at the end of 0, 1, 2, 3, and 6 months to detect the content of the main indicator components (paeoniflorin and cinnamaldehyde).

[0063] Results: After 6 months, the average retention rates of paeoniflorin and cinnamaldehyde in the three batches of samples were 96.5% and 95.8%, respectively, with RSDs of less than 2.0%. ICH guidelines stipulate that the content of a drug within its shelf life should not be less than 90% of the labeled amount. The average retention rates of paeoniflorin and cinnamaldehyde in the samples of this invention both exceeded 90%, indicating that the quality of this product is relatively stable.

[0064] Comparative Example 1: Verifying the retention effect of volatile components

[0065] Objective: To demonstrate that the inclusion process and soft capsule dosage form of the present invention are significantly superior to traditional decoctions and ordinary capsules without inclusion in terms of preserving the volatile active ingredients of cinnamon twig (represented by cinnamaldehyde).

[0066] method:

[0067] Prepare the following four types of samples:

[0068] Sample A (traditional decoction): Prepared according to the method described in the literature "Clinical observation on the treatment of patients with diastolic heart failure (Yang deficiency, blood stasis and water retention type) by combining Wu Ling San with Gui Zhi Fu Ling Wan".

[0069] Sample B (control capsule 1): prepared according to the method of Example 1, but omitting the β-cyclodextrin inclusion step in step 1, and directly mixing the volatile oil of cinnamon twig with the matrix.

[0070] Sample C (control soft capsule 2): prepared according to the method of Example 1, but the matrix in step 4 was changed, and the medium chain triglyceride (MCT) and polyethylene glycol 600 (PEG600) were adjusted to a single matrix - polyethylene glycol 400 (PEG400).

[0071] Sample D (soft capsule of the present invention): prepared strictly according to the method and parameters described in Example 1.

[0072] The four substances were placed under accelerated conditions (40℃±2℃, RH75%±5%) for 0 days, 30 days, and 90 days.

[0073] Samples were taken at various time points, and the content of cinnamaldehyde was determined by GC or HPLC.

[0074] result:

[0075] Table 3 Comparison of the retention effects of volatile components in four samples within 90 days

[0076]

[0077] Conclusion: The comparison between sample B (without inclusion complexation) and sample D (of this invention) demonstrates that omitting the β-cyclodextrin inclusion complexation process leads to a significant loss of cinnamaldehyde (retention rate decreased from 91.8% to 45.7%). This proves that the inclusion complexation process is indispensable for retaining active ingredients, and its effect is beyond the expectations of those skilled in the art.

[0078] Comparative Example 2: Controlled Experiment – ​​Verifying the Reduction in Gastrointestinal Irritation

[0079] Objective: To demonstrate that the inclusion process of the present invention can significantly reduce the irritation of cinnamon twig volatile oil to the stomach.

[0080] Method (Rats' gastric irritation test):

[0081] Fifty healthy SD rats were randomly divided into 5 groups (n=10):

[0082] Blank control group: Gavaged with an equal volume of physiological saline.

[0083] Decoction group: Sample A (traditional decoction) in Example 2, administered by gavage.

[0084] Control capsule group: Samples B (capsule contents without volatile oil) and C (capsule contents with conventional matrix) from Example 2, administered by gavage.

[0085] This invention group: Sample D (contents of the soft capsule of this invention) in Example 2 of gavage.

[0086] Each group was administered the equivalent amount of raw drug via gavage once daily for 7 consecutive days.

[0087] After the last administration, the animal was fasted for 24 hours, then sacrificed, and its stomach was removed and fixed in formalin.

[0088] Observe the gastric mucosal damage (such as ulcers, bleeding, edema) and perform histopathological scoring (0 points: normal; the higher the score, the more severe the damage).

[0089] result:

[0090] Table 4 Comparison of gastric mucosal damage in four samples

[0091]

[0092] Note: Compared with the decoction group and the control capsule group, p < 0.01, indicating a statistically significant difference.

[0093] Conclusion: The comparison between sample B (without inclusion complexation) and sample D (of this invention) demonstrates that omitting the β-cyclodextrin inclusion complexation process not only leads to a significant loss of cinnamaldehyde (retention rate decreased from 91.8% to 45.7%) but also a significant increase in irritation. This proves that the inclusion complexation process is indispensable for retaining active ingredients and reducing irritation, and its effect is beyond the expectations of those skilled in the art.

[0094] A comparison of sample C (conventional matrix) and sample D (this invention) demonstrates that the sample using the conventional PEG400 matrix exhibited severe hardening and precipitation, and its component retention rate and improvement in irritation were inferior to those of this invention. This proves that the specific composite matrix system (MCT / PEG600) used in this invention plays a crucial and unexpected role in maintaining the physical and chemical stability of the complex compound contents.

[0095] Comparative Example 3: Pharmacodynamic Experiment—Demonstrating the Synergistic Effect of the Combined Formula in Anti-Cardiac Aging

[0096] Experimental animals: 50 eight-month-old SPF-grade male accelerated aging mice (SAMP8) were randomly divided into 5 groups of 10 mice each to serve as a natural aging model.

[0097] Sample D (Invention Group): The contents of the soft capsule of the present invention (the complete formula of Wuling Powder and Guizhi Fuling Pill) were administered to mice by gavage according to the human equivalent dose.

[0098] Sample E (Wu Ling San group): soft capsule contents containing only Wu Ling San (cinnamon twig, poria cocos, polyporus umbellatus, alisma plantago-aquatica, and atractylodes macrocephala).

[0099] Sample F (Guizhi Fuling Pill Group): Soft capsules containing only Guizhi Fuling Pill (Guizhi, Fuling, Mudanpi, Taoren, Chishao).

[0100] Model control group: administered an equal volume of physiological saline by gavage.

[0101] Positive control group: Rapamycin was administered orally as a reference for efficacy.

[0102] After 12 weeks of continuous drug administration, mice in each group were lightly anesthetized by intraperitoneal injection of an appropriate amount of sodium pentobarbital, and the chest area was prepared for ultrasound imaging. Doppler echocardiography of each group of mice was performed using a small animal-specific high-frequency ultrasound imaging system, as shown in the attached figures. Figure 2 As shown, the ultrasound of mice in the positive control group showed a relatively normal diastolic function pattern; the ultrasound of mice in the model control group showed a typical diastolic dysfunction (Grade I) pattern; compared with the model group, the ultrasound of mice in sample E (Wu Ling San) showed an increase in the E peak and a decrease in the A peak; the ultrasound of mice in sample F (Gui Zhi Fu Ling Wan) showed an improvement pattern similar to that of sample E (Wu Ling San); the ultrasound of mice in sample D (the combined formula of this invention) showed the most significant functional improvement, and the E and A peaks were read.

[0103] Calculate the E / A ratio: Divide the peak E velocity by the peak A velocity, i.e., E / A ratio = peak E velocity / peak A velocity.

[0104] Table 5 Comparison of Cardiac Function Improvement Results

[0105]

[0106] The combination of the present invention is significantly more effective than any single-ingredient group in improving cardiac diastolic function (E / A ratio). The E / A ratio of the present invention is significantly higher than that of the model control group (p<0.05) and closer to that of the positive control group.

[0107] Comparative Example 4: Masson staining of myocardial tissue

[0108] Heart tissues from mice in Comparative Example 3, including the positive control group, model control group, sample E (Wu Ling San), sample F (Gui Zhi Fu Ling Wan), and sample D (the combined formula of this invention), were collected after the experiment.

[0109] Tissue fixation and sectioning: After fixation in 4% paraformaldehyde for 48 hours, cardiac tissue was routinely dehydrated and embedded in paraffin. Serial sections were prepared along the sagittal plane of the heart, with a thickness of 5 μm.

[0110] Dewaxing and hydration: Paraffin sections were dewaxed with xylene and hydrated with a gradient of ethanol (100%, 95%, 80%) to distilled water.

[0111] Nuclear staining: Stain with Weigert iron hematoxylin solution for 5-10 minutes, then rinse briefly with running water.

[0112] Differentiation: Differentiate with 1% hydrochloric acid ethanol for a few seconds, then rinse with running water to restore blue color.

[0113] Staining with slurry: Add Ponceau S Acid Fuchsin staining solution and stain for 5-10 minutes, then rinse briefly with a weak acid working solution.

[0114] Collagen fiber staining: Stain with aniline blue solution for 1-5 minutes, then rinse briefly with weak acid working solution.

[0115] Dehydration and mounting: Quickly dehydrate with 95% ethanol and anhydrous ethanol, clear with xylene, and mount with neutral resin.

[0116] Image acquisition and analysis: Five heart samples were randomly selected from each group, and five non-overlapping fields of view (400x magnification) were randomly captured from the free wall myocardial tissue of the left ventricle under an optical microscope for each sample.

[0117] Qualitative observation results (tissue morphology) show that, for example Figure 3 As shown. Positive control group: Cardiac cardiomyocytes are neatly arranged and dense, with red cytoplasm and almost no visible blue collagen fibers distributed around blood vessels. Model control group: A large number of bright blue collagen fibers are diffusely distributed between cardiomyocytes, forming a typical "blue grid," with widened intercellular spaces and disordered structure. This indicates that significant myocardial interstitial fibrosis was successfully established in the aging mouse model. Samples E and F: The area of ​​blue collagen fibers was reduced compared to the model control group, but still significantly more than that of the positive control group. Sample D (this invention): The myocardial tissue structure was significantly improved, with a significant reduction in blue collagen fiber deposition, and the cardiomyocytes were more densely arranged, with a morphology closest to the positive control group.

[0118] Comparative Example 5: Comparative Experiment of Inclusion Complexes Formed by Cinnamon Twig Volatile Oil and β-Cyclodextrin

[0119] Capsules with different weight ratios of β-cyclodextrin and cinnamon twig volatile oil were designed, and other steps were performed as described in Example 1. Accelerated testing was conducted according to the 2020 edition of the Chinese Pharmacopoeia, Part IV. After 90 days of accelerated testing, the content of cinnamaldehyde in each group was determined and the retention rate was calculated.

[0120] Table 6. Accelerated test of inclusion complex formed by volatile oil of cinnamon twig and β-cyclodextrin

[0121]

[0122] When the weight ratio of the inclusion compound was 4:1, the retention rate of cinnamaldehyde reached its peak. The retention rate of D3 (8:1) was slightly lower than that of D2 (4:1). The effect of D2 (4:1) was significantly better than that of the conventional choice D1 (2:1), proving that the inclusion effect is not linearly related to the amount of inclusion compound used.

[0123] Comparative Example 6: The inclusion compound and the matrix complex work synergistically.

[0124] With the weight of the extract fixed, only the composition of the excipients was changed, and the following 5 groups of experiments were designed. Other steps were the same as in Example 1. Accelerated tests were conducted according to the 2020 edition of the Chinese Pharmacopoeia, Part IV. After 90 days of accelerated testing, the content of cinnamaldehyde in each group was determined and the retention rate was calculated.

[0125] Table 7 Comparison of accelerated test results of inclusion complexes and matrix complexes with different weight ratios

[0126]

[0127] Under the premise of the same inclusion process, i.e., β-CD:oil ratio of 4:1, the weight ratio of S2 (1:2) inclusion complex to matrix complex has the best protective effect on cinnamaldehyde, proving that at this ratio, the matrix complex achieves the optimal "encapsulation" and "support" of the inclusion complex.

[0128] Comparing S2 and S4, with the exact same weight ratio of inclusion complex to matrix complex (1:2), the retention rates of S4 were significantly lower than those of S2 simply because the internal ratio of the inclusion complex changed from 4:1 to 8:1. This indicates that the inclusion complex and matrix complex of the present invention work synergistically, and the optimal protective effect is not achieved by a single excipient, but by the optimal synergy between the inclusion technology and the matrix complex.

[0129] "Composite proportioning parameter system".

[0130] The traditional Chinese medicine composition provided by this invention exerts a synergistic effect between its components. The prepared traditional Chinese medicine soft capsules effectively overcome the defects of traditional decoctions, such as inconvenience in carrying, unstable components, and strong irritation. It provides a modern traditional Chinese medicine preparation with controllable quality, high safety, and definite efficacy, and has significant technological progress and good prospects for industrial application.

[0131] It should be understood that the above embodiments are merely examples for clearly illustrating the present invention and are not intended to limit the implementation of the present invention. Those skilled in the art can make other variations based on the above description. It is neither necessary nor possible to exhaustively describe all possible implementations. Any modifications, equivalent substitutions, and improvements derived from this invention should be included within the scope of protection of the claims of this invention.

Claims

1. A traditional Chinese medicine composition for combating cardiac aging, characterized in that, The prescription dosage of the traditional Chinese medicine composition is as follows: 15-25 parts of cinnamon twig, 10-15 parts of polyporus umbellatus, 15-20 parts of poria cocos, 15-20 parts of alisma plantago-aquatica, 10-15 parts of atractylodes macrocephala, 10-15 parts of peony bark, 10-15 parts of peach kernel, and 10-15 parts of red peony root.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The prescription quantities of the traditional Chinese medicine composition are as follows: 20 parts of cinnamon twig, 12 parts of polyporus umbellatus, 18 parts of poria cocos, 18 parts of alisma plantago-aquatica, 12 parts of atractylodes macrocephala, 12 parts of peony bark, 12 parts of peach kernel, and 12 parts of red peony root.

3. A traditional Chinese medicine soft capsule for combating cardiac aging, characterized in that, The herbal soft capsule comprises the herbal composition according to claim 1 or claim 2 and pharmaceutical excipients, wherein the pharmaceutical excipients comprise inclusion compounds and matrix mixtures.

4. The traditional Chinese medicine soft capsule according to claim 3, characterized in that, The inclusion compound is selected from one or more of hydroxypropyl-β-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, cellulose acetate phthalate, and polylactic acid-glycolic acid copolymer.

5. The traditional Chinese medicine soft capsule according to claim 3, characterized in that, The matrix mixture is selected from two or more of medium-chain triglycerides, corn oil, soybean oil, palm kernel oil, polyethylene glycol 600, glycerol, and propylene glycol.

6. The traditional Chinese medicine soft capsule according to any one of claims 3-5, characterized in that, The inclusion compound is β-cyclodextrin, and the matrix mixture is medium-chain triglycerides and polyethylene glycol 600.

7. A method for preparing the traditional Chinese medicine soft capsule according to claim 3, characterized in that, The preparation method adopts a process route of "group extraction - instant inclusion - composite matrix mixing", including the following steps: (1) Extraction and inclusion of volatile oil from cinnamon twig: Take the prescribed amount of cinnamon twig, crush it, and collect the volatile oil and aromatic water by steam distillation. Slowly add the volatile oil to a saturated aqueous solution of β-cyclodextrin for immediate inclusion. Reserve the aromatic water. Keep the cinnamon twig residue. (2) Water extraction: The cinnamon twig residue obtained in step (1) is mixed with the prescribed amounts of Polyporus umbellatus, Poria cocos, Alisma plantago-aquatica, Atractylodes macrocephala, Paeonia suffruticosa, Prunus persica, and Paeonia lactiflora. Water is added for dynamic circulation extraction, and the mixture is filtered and the filtrates are combined. (3) Concentration: Combine the filtrate obtained in step (2) with the aromatic water obtained in step (1) and concentrate under reduced pressure to a clear extract with a relative density of 1.10-1.15; (4) Preparation of contents: Mix the clear paste obtained in step (3) with the volatile oil of cinnamon twig obtained in step (1) and the matrix, grind evenly to obtain the contents of soft capsules; (5) Squashing and drying: The contents and gelatin solution are squashed together, and after shaping, they are washed and dried to obtain the soft capsules.

8. The method for preparing traditional Chinese medicine soft capsules according to claim 7, characterized in that, In step (1), the weight ratio of β-cyclodextrin to volatile oil is 2:1 to 5:1, and the mixture is stirred at a constant temperature of 50°C for 2 hours. The steam distillation process involves adding 7-10 times the amount of water and distilling for 4-6 hours. In step (2), the dynamic cyclic extraction conditions are: adding 8-10 times the amount of water, extracting twice, and each extraction lasts for 1-2 hours. In step (3), the concentration conditions are: temperature 50-70℃ and pressure -0.06MPa to -0.10MPa.

9. The method for preparing traditional Chinese medicine soft capsules according to claim 7, characterized in that, In step (4), the matrix is ​​a mixture of medium-chain triglycerides and polyethylene glycol 600 in a weight ratio of 1:1 to 1:2; the weight ratio of the clear paste, cinnamon twig volatile oil inclusion complex to the matrix is ​​1:(0.1-0.4) to 1:(0.6-0.8).

10. The use of the traditional Chinese medicine composition of claim 1 or the traditional Chinese medicine soft capsule of claim 3 in the preparation of a drug for treating cardiac aging, myocardial fibrosis, decreased cardiac function, or metabolic heart disease.

Images