Traditional Chinese medicine composition and traditional Chinese medicine preparation for treating myocardial ischemia-reperfusion injury

Abstract

The invention provides a traditional Chinese medicine composition and a traditional Chinese medicine preparation for treating myocardial ischemia-reperfusion injury. The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 10-15 parts of salvia miltiorrhiza, 10-15 parts of radix astragali preparata, 7-11 parts of allium macrostemon, 7-11 parts of cassia twig, 4-8 parts of sandalwood, 4-8 parts of fructus amomi, 7-11 parts of herba epimedii, 10-15 parts of codonopsis pilosula and 3-4 parts of pseudo-ginseng. The traditional Chinese medicine composition follows a method of tonifying qi, warming yang and activating blood, can improve key pathological links such as reperfusion energy metabolism disorder, oxidative stress and inflammatory response, microcirculation disturbance and the like, and is suitable for prevention and treatment of myocardial ischemia reperfusion injury.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine composition technology, and in particular to a traditional Chinese medicine composition and preparation for treating myocardial ischemia-reperfusion injury (MIRI). Background Technology

[0002] Myocardial ischemia-reperfusion (including thrombolysis and percutaneous coronary intervention) can significantly reduce mortality, but reperfusion itself can induce oxidative stress, calcium overload, abnormal opening of the mitochondrial permeability transition pore (mPTP), inflammatory response, and microcirculatory disturbances, manifesting as a series of injury phenotypes such as cardiomyocyte apoptosis / necrosis, interstitial edema, and "no-reflow." Current drugs such as antiplatelet drugs, beta-blockers, nitrates, and statins can partially improve prognosis, but their intervention on reperfusion injury involving multiple pathways is limited, and long-term use is easily limited by adverse reactions such as hypotension and abnormal liver and kidney function. The lack of a comprehensive regulatory strategy that takes into account energy metabolism, mitochondrial homeostasis, and inflammatory response is one of the current treatment challenges.

[0003] Traditional Chinese medicine classifies acute angina pectoris as a condition of deficiency in the root and excess in the branch. The root deficiency is primarily qi deficiency, while the branch excess is often blood stasis and yang stagnation. During the reperfusion phase, the disease progresses rapidly, making it especially important to tonify qi to strengthen the root, warm yang to invigorate heart yang, and promote blood circulation to unblock the channels and remove blood stasis. Clinically available compound prescriptions often emphasize one aspect and fail to address all three aspects in a balanced way, thus easily leading to unstable efficacy and recurring symptoms. Summary of the Invention

[0004] This invention proposes a traditional Chinese medicine composition and preparation for treating myocardial ischemia-reperfusion injury. Following the principle of invigorating qi, warming yang, and promoting blood circulation, it can improve key pathological aspects such as energy metabolism disorders, oxidative stress and inflammatory response, and microcirculatory disturbances during the reperfusion period. It is suitable for the prevention and treatment of myocardial ischemia-reperfusion injury.

[0005] The technical solution of the present invention is implemented as follows: a traditional Chinese medicine composition for treating myocardial ischemia-reperfusion injury is prepared from the following raw materials in parts by weight: 10-15 parts of Salvia miltiorrhiza, 10-15 parts of Astragalus membranaceus (processed), 7-11 parts of Allium macrostemon, 7-11 parts of Cinnamomum cassia, 4-8 parts of Santalum album, 4-8 parts of Amomum villosum, 7-11 parts of Epimedium brevicornu, 10-15 parts of Codonopsis pilosula, and 3-4 parts of Panax notoginseng.

[0006] Furthermore, the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 12 parts of Salvia miltiorrhiza, 12 parts of Astragalus membranaceus (processed), 9 parts of Allium macrostemon, 9 parts of Cinnamomum cassia, 6 parts of Santalum album, 6 parts of Amomum villosum, 9 parts of Epimedium brevicornu, 12 parts of Codonopsis pilosula, and 3 parts of Panax notoginseng.

[0007] A method for preparing a traditional Chinese medicine composition for treating myocardial ischemia-reperfusion injury includes the following steps: (1) Take Salvia miltiorrhiza, Astragalus membranaceus (processed), Allium macrostemon, Cinnamomum cassia, Santalum album, Epimedium brevicornu, Codonopsis pilosula and Panax notoginseng, add water and decoct, filter the extract and concentrate it under reduced pressure into a thick paste; (2) Grind the cardamom into a fine powder and add it to the thick paste in step (1), and mix evenly. Add the cardamom last to protect the aromatic volatile and heat-sensitive components.

[0008] Further, in step (1), add 8-12 times the weight of water, decoct twice, 1 hour each time, and combine the extracts.

[0009] A traditional Chinese medicine preparation for treating myocardial ischemia-reperfusion injury, prepared from the aforementioned traditional Chinese medicine composition.

[0010] Furthermore, the traditional Chinese medicine preparation is an oral liquid, granules, tablets, or capsules.

[0011] Furthermore, the oral liquid is an aqueous solution.

[0012] The traditional Chinese medicine composition is used to prepare a drug for treating myocardial ischemia-reperfusion injury.

[0013] The beneficial effects of this invention are: For myocardial ischemia-reperfusion injury, the traditional Chinese medicine composition of this invention (hereinafter referred to as: Danqi Tongxin Formula) uses Astragalus membranaceus and Codonopsis pilosula as the chief ingredients to invigorate Qi, consolidate the body's resistance, and help maintain energy metabolism; Cinnamomum cassia and Epimedium brevicornu are used as the assistant ingredients to warm Yang; Allium macrostemon regulates Qi and relieves chest tightness; and Santalum album promotes Qi circulation and relieves pain to help smooth the body's functions; Salvia miltiorrhiza and Panax notoginseng are used as adjuvant ingredients to invigorate blood and unblock collaterals, synergistically improving microcirculation and removing blood stasis; and Amomum villosum invigorates the spleen and harmonizes the middle Jiao as the guiding ingredient, and is added later to protect the aromatic components. In summary, the formula achieves the effects of invigorating Qi and warming Yang, invigorating blood and unblocking collaterals, and regulating Qi and relieving chest tightness, and can be used for comprehensive regulation of multiple aspects during the reperfusion period.

[0014] The Danqi Tongxin Formula of this invention takes the method of invigorating qi, warming yang, and activating blood circulation as its core principle: invigorating qi to strengthen the foundation and nourish the source, warming yang to invigorate the heart yang and unblock the body's mechanisms, and activating blood circulation to unblock the collaterals, remove blood stasis, and help restore microcirculation. The three methods complement each other, taking into account both the deficiency of qi and yin and the excess of blood stasis and stagnation of yang, thereby forming a comprehensive regulation of energy metabolism, mitochondrial homeostasis, oxidative stress, inflammatory response, and microcirculatory disorders during myocardial reperfusion.

[0015] To verify the effectiveness of the herbal composition of this invention, an experimental study was conducted using a myocardial ischemia-reperfusion model in SD rats with left anterior descending artery (LAD) ligation for 45 minutes followed by reperfusion for 24 hours. The results showed that the infarct area in the Danqi Tongxin Formula intervention group was significantly smaller than that in the model group, as indicated by TTC staining. HE staining revealed a more intact myocardial fiber structure with reduced necrosis and inflammatory infiltration. Masson staining indicated decreased collagen deposition and a reduced degree of fibrosis. Serum levels of CK-MB and cTnI were significantly lower, indicating that myocardial cell membrane permeability damage was alleviated.

[0016] Meanwhile, Danqi Tongxin Formula significantly inhibited the expression of inflammatory factors TNF-α, IL-1β, IL-6, and IL-18, downregulated the inflammatory response, reduced the content of oxidative stress product MDA, increased the levels of antioxidant enzymes SOD and GSH, and decreased LDH activity, suggesting that it has a protective effect against cell necrosis and metabolic disorders. The overall results indicate that Danqi Tongxin Formula, through a three-pronged approach of "tonifying qi, warming yang, and activating blood circulation," can synergistically exert its effects on multiple aspects during reperfusion, achieving systemic protection against myocardial injury from the levels of energy metabolism, antioxidation, anti-inflammation, and microcirculation. Attached Figure Description

[0017] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0018] Figure 1 Echocardiography of rats in each group; Figure 2 Comparison of cardiac function indices by color Doppler echocardiography in rats of different groups; Figure 3 Comparison of myocardial injury marker levels among different groups of rats; Figure 4 The degree of myocardial fibrosis in each group of rats (Masson staining, ×200); Figure 5 Pathological morphology of myocardial tissue in rats of each group (HE staining, ×200); Figure 6 Comparison of myocardial injury marker levels among different groups of rats; Figure 7 Comparison of oxidative stress levels among rats in each group; Figure 8 Comparison of TTC staining results in the hearts of rats in each group.

[0019] Data were analyzed using one-way ANOVA. A p-value < 0.05 was considered statistically significant. * indicates comparison with the sham surgery group; # indicates comparison with the model group; *p < 0.05, **p < 0.01, ***p < 0.001; #p < 0.05, ##p < 0.01, ###p < 0.001. Detailed Implementation

[0020] 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.

[0021] Example 1

[0022] The traditional Chinese medicine composition for treating myocardial ischemia-reperfusion injury (abbreviated as Danqi Tongxin Formula) is prepared from the following raw materials in parts by weight: 12 parts of Salvia miltiorrhiza, 12 parts of Astragalus membranaceus (processed), 9 parts of Allium macrostemon, 9 parts of Cinnamomum cassia, 6 parts of Santalum album, 6 parts of Amomum villosum, 9 parts of Epimedium brevicornu, 12 parts of Codonopsis pilosula, and 3 parts of Panax notoginseng.

[0023] The preparation method of the traditional Chinese medicine composition includes the following steps: (1) Weigh out the following ingredients according to the ratio: Salvia miltiorrhiza, Astragalus membranaceus (processed), Allium macrostemon, Cinnamomum cassia, Santalum album, Epimedium brevicornu, Codonopsis pilosula and Panax notoginseng. Add 8-12 times the weight of water, decoct twice, 1 hour each time, combine the extracts, filter the extracts, and concentrate under reduced pressure into a thick paste. (2) Grind the cardamom into a fine powder and add it to the thick paste in step (1), mix evenly to obtain the active ingredient.

[0024] A traditional Chinese medicine preparation for treating myocardial ischemia-reperfusion injury, prepared from the aforementioned traditional Chinese medicine composition. The traditional Chinese medicine preparation is an oral liquid, granules, tablets, or capsules.

[0025] The oral liquid is an aqueous preparation, and the specific preparation method is as follows: The active ingredient prepared in step (2) of Example 1 is dissolved in an appropriate amount of purified water and brought to a final volume. If necessary, it is clarified and filtered or filtered through a suitable membrane. The pH is adjusted to 5.5-6.5, and an appropriate amount of sodium chloride is added to control the osmotic pressure of the preparation at 260-320 mOsm / kg, so that it is basically equivalent to the osmotic pressure of human plasma. It is sterilized under sealed conditions, aseptically filled and dispensed into heat-resistant containers, sealed, and after passing the inspection, the oral liquid of traditional Chinese medicine preparation is obtained. Clarification, filtration, sterilization, and aseptic dispensing ensure stability and microbiological safety. If other dosage forms are to be prepared, the active ingredient can be combined with excipients to make granules, tablets, or capsules, and the method is carried out according to the conventional process in this field.

[0026] An SD rat myocardial ischemia-reperfusion model was established, and the animals were healthy, with body weights and genders meeting the requirements of laboratory animal science. The model was created by ligating the left anterior descending branch for 45 minutes followed by 24 hours of reperfusion. The experiments included a blank group, a sham operation group, a model group, a low-dose DQTX group, a medium-dose DQTX group, a high-dose DQTX group, and a trimetazidine group. The blank group received no treatment; the sham operation group only had the chest opened without coronary artery ligation; the model group had the left anterior descending branch ligated for 45 minutes followed by 24 hours of reperfusion to establish the ischemia-reperfusion model. DQTX is the abbreviation of Danshen Qitong Decoction.

[0027] The aqueous solution was prepared as the administration preparation according to the above method, and intragastric administration was carried out according to the principle of body surface area conversion. The low-dose DQTX group was given DQTX (aqueous solution) at 4.10 g·kg -1 ·d -1 , the medium-dose group was given 8.19 g·kg -1 ·d -1 , the high-dose group was given 16.38 g·kg -1 ·d -1 , which were 0.5 times, 1 times, and 2 times the clinically common doses respectively. The trimetazidine group was given trimetazidine at 20 mg·kg -1 ·d -1 . All groups were continuously intragastrically administered for 14 days before model establishment, and then the surgery was performed according to the above method to establish the model. The sampling time point was 24 hours of reperfusion. Histology used TTC staining to evaluate the infarction area, HE staining to observe histological damage and inflammatory infiltration, and Masson staining to evaluate collagen deposition and fibrosis degree.

[0028] Serum was detected for myocardial injury markers CK-MB, cTnI; inflammatory factors TNF-α, IL-6, IL-1β, IL-18; oxidative stress and antioxidant indexes MDA, SOD, GSH; cell necrosis and membrane permeability-related index LDH. According to the comparison with the model group, the improvement trends of the infarction area, histological damage, and the above biochemical indexes were evaluated.

[0029] It was known from Figure 1 and Figure 2 that compared with the blank group and the sham operation group, the CO, EF, and FS of the rats in the model group significantly decreased. Compared with the model group, the above cardiac function indexes in each DQTX dose group improved, indicating that DQTX can improve the cardiac function of MIRI rats.

[0030] It was known from Figure 3 that compared with the model group, the serum levels of CK-MB and cTnI in the Danshen Qitong Decoction (DQTX) administration group decreased, indicating that the damage to the myocardial cell membrane permeability was relieved, and the decrease in LDH indicated that cell necrosis and metabolic disorders were alleviated.

[0031] It was known from Figure 4 It was found that the blank control group and the sham surgery group had well-organized myocardial fibers, minimal collagen deposition, and maintained intact cardiac tissue structure, exhibiting the lowest level of fibrosis. The model group, however, showed significant pathological changes, with disordered myocardial fiber arrangement, a marked increase in collagen fiber (blue) deposition, and a substantial increase in interstitial fibrosis area. In each DQTX dose group, the degree of myocardial fibrosis gradually decreased with increasing drug dosage. This suggests that DQTX can significantly improve MIRI-induced myocardial fibrosis.

[0032] Depend on Figure 5 It was found that the myocardial morphology of rats in the blank group and sham-operated group was normal, with myocardial fibers arranged tightly and neatly, and cell structure intact, without obvious pathological changes. Compared with the sham-operated group, the myocardial tissue of rats in the model group was significantly damaged, manifested as myocardial fiber breakage and disordered arrangement, significant interstitial edema, and a large number of inflammatory cell infiltrations. Compared with the model group, the myocardial structure of the low-dose DQTX group was improved, but some myocardial fibers were still irregularly arranged and there was mild interstitial edema. The myocardial damage of the medium- and high-dose DQTX groups was significantly reduced, the myocardial fiber arrangement tended to be regular, and the interstitial edema and inflammatory infiltration were significantly reduced. The high-dose group had a particularly significant effect, suggesting that DQTX can improve the histopathological changes caused by MIRI.

[0033] Depend on Figure 6 It can be seen that, compared with the model group, the levels of TNF-α, IL-6, IL-1β and IL-18 in the Danqi Tongxin Formula (DQTX) administration group were reduced, and the inflammatory response was suppressed.

[0034] Depend on Figure 7 It can be seen that, compared with the model group, the MDA level of the Danqi Tongxin Formula (DQTX) administration group was reduced while the SOD and GSH levels were increased, and the antioxidant capacity was enhanced.

[0035] Depend on Figure 8 It can be seen that, compared with the model group, the infarct size was reduced in the DQTX group; Therefore, animal experiments show that Danqi Tongxin Formula, through its combination strategy of invigorating qi, warming yang, and promoting blood circulation, simultaneously improves key aspects such as histological damage, myocardial injury markers, inflammation, and oxidative stress during the reperfusion period, demonstrating its comprehensive protective potential against myocardial ischemia-reperfusion injury.

[0036] Example 2

[0037] This embodiment is basically the same as Embodiment 1, except that the traditional Chinese medicine composition for treating myocardial ischemia-reperfusion injury is prepared from the following raw materials in parts by weight: 10 parts of Salvia miltiorrhiza, 10 parts of Astragalus membranaceus (processed), 8 parts of Allium macrostemon, 7 parts of Cinnamomum cassia, 4 parts of Santalum album, 4 parts of Amomum villosum, 7 parts of Epimedium brevicornu, 10 parts of Codonopsis pilosula, and 3 parts of Panax notoginseng.

[0038] Example 3

[0039] This embodiment is basically the same as Embodiment 1, except that the traditional Chinese medicine composition for treating myocardial ischemia-reperfusion injury is prepared from the following raw materials in parts by weight: 15 parts of Salvia miltiorrhiza, 15 parts of Astragalus membranaceus (processed), 11 parts of Allium macrostemon, 10 parts of Cinnamomum cassia, 7 parts of Santalum album, 8 parts of Amomum villosum, 11 parts of Epimedium brevicornu, 15 parts of Codonopsis pilosula, and 4 parts of Panax notoginseng.

[0040] Example 4

[0041] This embodiment is basically the same as Embodiment 1, except that the traditional Chinese medicine composition for treating myocardial ischemia-reperfusion injury is prepared from the following raw materials in parts by weight: 12 parts of Salvia miltiorrhiza, 12 parts of Astragalus membranaceus (processed), 10 parts of Allium macrostemon, 10 parts of Cinnamomum cassia, 8 parts of Santalum album, 7 parts of Amomum villosum, 10 parts of Epimedium brevicornu, 12 parts of Codonopsis pilosula, and 4 parts of Panax notoginseng.

[0042] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition for treating myocardial ischemia-reperfusion injury, characterized in that: It is prepared from the following raw materials in parts by weight: 10-15 parts of Salvia miltiorrhiza, 10-15 parts of Astragalus membranaceus (processed), 7-11 parts of Allium macrostemon, 7-11 parts of Cinnamomum cassia, 4-8 parts of Santalum album, 4-8 parts of Amomum villosum, 7-11 parts of Epimedium brevicornu, 10-15 parts of Codonopsis pilosula, and 3-4 parts of Panax notoginseng.

2. The traditional Chinese medicine composition for treating myocardial ischemia-reperfusion injury according to claim 1, characterized in that: The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 12 parts of Salvia miltiorrhiza, 12 parts of Astragalus membranaceus (processed), 9 parts of Allium macrostemon, 9 parts of Cinnamomum cassia, 6 parts of Santalum album, 6 parts of Amomum villosum, 9 parts of Epimedium brevicornu, 12 parts of Codonopsis pilosula, and 3 parts of Panax notoginseng.

3. The method for preparing the traditional Chinese medicine composition for treating myocardial ischemia-reperfusion injury as described in claim 1 or 2, characterized in that, Includes the following steps: (1) Take Salvia miltiorrhiza, Astragalus membranaceus (processed), Allium macrostemon, Cinnamomum cassia, Santalum album, Epimedium brevicornu, Codonopsis pilosula and Panax notoginseng, add water and decoct, filter the extract and concentrate it under reduced pressure into a thick paste; (2) Grind the cardamom into a fine powder and add it to the thick paste in step (1) and mix evenly.

4. The preparation method according to claim 3, characterized in that, In step (1), add 8-12 times the weight of water, decoct twice, 1 hour each time, and combine the extracts.

5. A traditional Chinese medicine preparation for treating myocardial ischemia-reperfusion injury, prepared from the traditional Chinese medicine composition according to claim 1 or 2.

6. The traditional Chinese medicine preparation according to claim 5, characterized in that: The traditional Chinese medicine preparations mentioned are oral liquids, granules, tablets, or capsules.

7. The traditional Chinese medicine preparation according to claim 6, characterized in that: The oral liquid is an aqueous solution.

8. The use of the traditional Chinese medicine composition according to claim 1 or 2, characterized in that: It is used to prepare drugs for treating myocardial ischemia-reperfusion injury.

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