A Chinese medicine composition for treating type 2 diabetes with orthostatic hypotension and its application

Abstract

The present invention relates to the technical field of traditional Chinese medicine, and in particular to a traditional Chinese medicine composition for treating type 2 diabetes with postural hypotension and its application. The traditional Chinese medicine composition is prepared from the following raw materials in effective amounts: raw astragalus, codonopsis, pseudostellaria, angelica, dendrobium, polygonatum, amomum, immature bitter orange, magnolia bark, tuckahoe, tangerine peel, pinellia, calamus and licorice. The traditional Chinese medicine composition has a scientific and rigorous formula and is used for treating type 2 diabetes with postural hypotension, and has the effect of significantly improving the patient's traditional Chinese medicine symptoms, cognitive ability, blood pressure values ​​and changes in different body positions and body position changes, and has obvious clinical treatment effect.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and in particular to a traditional Chinese medicine composition for treating type 2 diabetes with orthostatic hypotension and application thereof. Background Art

[0002] In recent years, the prevalence of type 2 diabetes mellitus (T2DM) has been gradually increasing. Orthostatic hypotension (OH) is one of the common complications of diabetes, which can cause symptoms such as dizziness, amaurosis, precordial discomfort, and general fatigue. In severe cases, syncope and even sudden death may occur [1,2]. The incidence of OH in elderly patients with type 2 diabetes mellitus (DM) is 28-30.5% [3,4]. Our study found that patients with diabetes and orthostatic hypotension had temporary impairment of executive function, memory, visual space, information processing speed and attention when standing, which directly confirmed that orthostatic hypotension affects cognitive function in diabetic patients [5].

[0003] At present, clinical guidelines emphasize that the disease should be treated mainly with non-drug intervention, which can be supplemented with midodrine hydrochloride. In recent years, traditional Chinese medicine has achieved good results in relieving diabetic patients' neurological complications and improving their quality of life. However, there are no reports of effective therapeutic drugs specifically for type 2 diabetes with orthostatic hypotension.

[0004] References:

[0005] [1] Gannon J, Claffey P, Laird E, et al. The cross-sectional association between diabetes and orthostatic hypotension in community-dwelling older people. Diabet Med. 2020; 37:1299-1307.

[0006] [2]Gaspar L, Kruzliak P, Komornikova A, et al. Orthostatic hypotension indiabetic patients-10-year follow-up study. J Diabetes Complications. 2016; 30:67-71.

[0007] [3] Van Hateren KJ, Kleefstra N, Blanker MH, et al. Orthostatic hypotension, diabetes, and falling in older patients: a cross-sectional study. Brit J General Pract 2012;62:e696–e702.

[0008] [4] Bouhanick B, Meliani S, Doucet J, et al. Orthostatic hypotension is associated with more severe hypertension in elderly autonomous diabetic patients from the French Gerodiab study at inclusion. Ann Cardiol Angeiol (Paris) 2014; 63:176–182.

[0009] [5] Zhang JB, Chi HY, Wang T, et al. Effects of orthostatic hypotension oncognition in type 2diabetes mellitus. Ann Neurol. 2019; 86:754-761.

[0010] [6] State Administration of Traditional Chinese Medicine. Guidelines for Clinical Research of New Drugs (Trial) [S]. Beijing: China Medical Science and Technology Press, 2002: 383.

[0011] [7] Sun Hongji, Xie Yue, Zhang Xiaohong, et al. Application of the Montreal Cognitive Assessment Scale in healthy people undergoing physical examinations[J]. Chinese Journal of Geriatric Cardiovascular and Cerebrovascular Diseases, 2014, 16(2): 174-177. Summary of the invention

[0012] The present invention provides a Chinese medicine composition for treating type 2 diabetes with orthostatic hypotension and its application. The Chinese medicine composition has a scientific and rigorous formula and compatibility, and is used for treating type 2 diabetes with orthostatic hypotension, and has the effect of significantly improving the patient's traditional Chinese medicine symptoms, cognitive ability, blood pressure values ​​and changes in different body positions and changes in body positions, has obvious clinical treatment effect, and solves the problems existing in the prior art.

[0013] The present invention provides the following technical solutions:

[0014] A traditional Chinese medicine composition for treating type 2 diabetes with orthostatic hypotension is prepared from the following raw materials in therapeutically effective amounts: astragalus, codonopsis, pseudostellaria, angelica, dendrobium, polygonatum, amomum, immature bitter orange, magnolia bark, tuckahoe, tangerine peel, pinellia, calamus and roasted liquorice.

[0015] Furthermore, the weight proportions of the above raw materials are as follows: 45-55 grams of raw astragalus, 25-35 grams of Codonopsis pilosula, 25-35 grams of Pseudostellaria pseudoginseng, 9-11 grams of Angelica sinensis, 15-25 grams of Dendrobium officinale, 15-25 grams of Polygonatum sibiricum, 5-15 grams of Amomum villosum, 10-20 grams of Citrus aurantium, 10-20 grams of Magnolia officinalis, 15-25 grams of Poria cocos, 5-15 grams of Citrus reticulata, 10-20 grams of Pinellia ternata, 4-8 grams of Acorus calamus, and 6-12 grams of roasted Licorice root.

[0016] Furthermore, the weight proportions of each raw material are as follows: 50 grams of raw astragalus, 30 grams of Codonopsis pilosula, 30 grams of Pseudostellaria pseudoginseng, 10 grams of Angelica sinensis, 20 grams of Dendrobium officinale, 20 grams of Polygonatum sibiricum, 10 grams of Amomum villosum, 15 grams of Citrus aurantium, 15 grams of Magnolia officinalis, 20 grams of Poria, 10 grams of Citrus reticulata, 15 grams of Pinellia ternata, 6 grams of Acorus calamus, and 9 grams of roasted Licorice root.

[0017] Furthermore, the above dosage form is decocted, concentrated and dried into sugar-free granules.

[0018] Furthermore, the Chinese medicine composition of the present invention is prepared as follows: cold water is added to soak the medicinal material surface for 2-3 cm, preferably, and soak for about 1 hour; when decocting Amomum villosum, it should be added later, and put into the container for decocting 5-10 minutes before other drugs are decocted. The Chinese medicine is decocted twice and the liquid is combined, extracted, concentrated and dried, and sugar-free granules are prepared, and each set is divided into two packages.

[0019] The present invention also provides the following technical solutions:

[0020] Use of the traditional Chinese medicine composition as described above in the preparation of a drug for treating type 2 diabetes associated with orthostatic hypotension.

[0021] Dosage: Take one pack each time, twice a day. The course of treatment is 4 weeks.

[0022] Beneficial effects of the present invention:

[0023] The Chinese medicine composition of the present invention is composed of the Buzhong Yiqi Decoction mentioned in "Spleen and Stomach Theory" by Li Dongyuan, one of the four great doctors of the Jin and Yuan Dynasties, and the compatibility is scientific and rigorous. In the prescription, raw Astragalus is used as the main medicine, which greatly replenishes the qi of the lungs and spleen and raises the yang and lifts the sunken; Codonopsis and Radix Pseudostellariae strengthen the spleen and replenish qi, and are the ministerial medicines; Angelica nourishes blood and harmonizes blood, and helps Astragalus, Codonopsis and Radix Pseudostellariae to replenish qi and blood; Dendrobium nourishes the stomach and produces fluid, nourishes yin and clears heat; Polygonatum sibiricum strengthens the spleen and moistens the lungs, produces fluid and moisturizes dryness, and plays the role of nourishing yin and moisturizing dryness, so as to prevent the tendency of thirst and yin deficiency. Amomum villosum promotes qi and regulates the middle, wakes up the spleen and harmonizes the stomach; Citrus aurantium breaks qi and eliminates accumulation, and eliminates fullness and distension; Magnolia officinalis promotes qi and eliminates accumulation, dries dampness and eliminates fullness. The above three flavors dredge the qi mechanism to prevent the tonic from stagnating and turning into heat and damaging yin and fluid. Poria strengthens the spleen, removes dampness and calms the mind; Tangerine peel promotes qi and relieves fullness, strengthens the spleen, dries dampness and resolves phlegm; Pinellia ternata dries dampness and resolves phlegm. The three remove dampness to relieve the spleen's troubles and help the spleen to rise. Acorus calamus is aromatic and awakens the spleen and opens the orifices, removes dampness and harmonizes the stomach, and improves the spleen and stomach functions. Roasted licorice harmonizes the various medicines and also has the effect of strengthening the spleen, replenishing qi and restoring the pulse. The above medicines treat both the symptoms and the root causes, replenishing qi and nourishing yin, raising the clear and lowering the turbid, regulating qi and removing dampness, without the disadvantages of dampness and stagnation of heat.

[0024] Clinical trial observations have shown that this Chinese medicine composition can be used to treat type 2 diabetes with orthostatic hypotension, and can significantly improve the patient's disease symptoms, blood pressure, cognitive function, etc. in different body positions, with significant clinical efficacy. DETAILED DESCRIPTION

[0025] In order to clearly illustrate the technical features of this solution, the present invention is described in detail below through specific implementation methods.

[0026] The instruments, reagents, materials, etc. involved in the following embodiments, unless otherwise specified, are all conventional instruments, reagents, materials, etc. in the prior art and can be obtained through regular commercial channels. The experimental methods, detection methods, etc. involved in the following embodiments, unless otherwise specified, are all conventional experimental methods, detection methods, etc. in the prior art.

[0027] Example 1

[0028] The Chinese medicine composition for treating type 2 diabetes with orthostatic hypotension is prepared from the following raw materials of active ingredients: 50 grams of raw astragalus, 30 grams of codonopsis pilosula, 30 grams of pseudostellaria, 10 grams of angelica, 20 grams of dendrobium, 20 grams of polygonatum, 10 grams of amomum, 15 grams of immature bitter orange, 15 grams of magnolia bark, 20 grams of tuckahoe, 10 grams of tangerine peel, 15 grams of pinellia, 6 grams of calamus, and 9 grams of roasted liquorice.

[0029] Example 2

[0030] The Chinese medicine composition for treating type 2 diabetes with orthostatic hypotension is prepared from the following raw materials of active ingredients: 45 grams of raw astragalus, 25 grams of codonopsis pilosula, 25 grams of pseudostellaria, 9 grams of angelica, 20 grams of dendrobium, 20 grams of polygonatum, 10 grams of amomum, 18 grams of immature bitter orange, 18 grams of magnolia bark, 20 grams of tuckahoe, 10 grams of tangerine peel, 12 grams of pinellia, 6 grams of calamus, and 9 grams of roasted liquorice.

[0031] Example 3

[0032] The Chinese medicine composition for treating type 2 diabetes with orthostatic hypotension is prepared from the following raw materials of active ingredients: 52 grams of raw astragalus, 32 grams of codonopsis pilosula, 32 grams of pseudostellaria, 12 grams of angelica, 20 grams of dendrobium, 20 grams of polygonatum, 10 grams of amomum, 18 grams of immature bitter orange, 18 grams of magnolia bark, 21 grams of tuckahoe, 12 grams of tangerine peel, 15 grams of pinellia, 6 grams of calamus, and 9 grams of roasted liquorice.

[0033] The preparation process of the Chinese medicine composition in the above embodiments is as follows:

[0034] 1. Clinical Data and Methods

[0035] 1.1 Diagnostic criteria: ① Patients with type 2 diabetes were diagnosed in accordance with the 1999 WHO diagnostic criteria for diabetes, with a course of disease of ≥ 3 years; ② The diagnosis of orthostatic hypotension was based on the diagnostic criteria for orthostatic hypotension published by the American Academy of Neurology in 1996 [4]: ​​within 3 minutes of the subject changing position (from supine to upright), the systolic blood pressure (SBP) decreased by ≥ 20 mmHg (1 mmHg = 0.133 kPa) and / or the diastolic blood pressure (DBP) decreased by ≥ 10 mmHg, with or without symptoms such as dizziness, headache, and fatigue. ③ TCM diagnosis was based on the Internal Medicine of Traditional Chinese Medicine [7], and the syndrome differentiation was classified as qi and yin deficiency with blood stasis, with the main symptoms including dizziness, fatigue, and headache; the secondary symptoms included hot flashes, night sweats, fever in the five parts of the body, and shortness of breath.

[0036] 1.2 Exclusion criteria: ① patients with normal cognition or severe cognitive impairment that affects written and verbal expression; ② patients with severe aphasia or dysarthria; ③ patients with neurological and psychiatric diseases (degenerative and / or vascular dementia, Parkinson's disease, stroke and severe depression), severe multi-organ diseases (anemia, lung disease, cancer) and other diseases that affect cognition; ④ patients with other serious physical diseases or severe abnormalities of thyroid, liver and kidney function; ⑤ patients who are allergic to the test drugs or have obvious gastrointestinal symptoms such as intolerance.

[0037] 1.3 Treatment Methods: Control group: conventional treatment, including reasonable exercise, diet, lifestyle changes and other non-drug treatments, and drugs for treating type 2 diabetes. Treatment group: the Chinese medicine composition product of the present invention is added to the treatment of the control group.

[0038] The prescription is selected from Example 1 of the present invention: 50 grams of raw astragalus, 30 grams of codonopsis, 30 grams of pseudoginseng, 10 grams of angelica, 20 grams of dendrobium, 20 grams of polygonatum, 10 grams of amomum, 15 grams of immature bitter orange, 15 grams of magnolia bark, 20 grams of tuckahoe, 10 grams of dried orange peel, 15 grams of pinellia, 6 grams of calamus, and 9 grams of licorice. Function: tonify the middle and replenish qi, raise yang and lift the sunken. Usage and dosage: the above dosage form is decocted, concentrated and dried into sugar-free granules, each pack is divided into two packs, one pack is taken each time, twice a day. The course of treatment is 4 weeks.

[0039] 1.4 Observation indicators: ① TCM symptom score: The symptoms of dizziness, headache, fatigue, shortness of breath, fever in the five parts of the body, and hot flashes and night sweats were scored before and after treatment in the two groups according to the relevant TCM quantitative scoring principles of the "Guidelines for Clinical Research of New Chinese Medicines" [6]. 0 points = none, 1 point = mild, 2 points = moderate, and 3 points = severe, and the total score was calculated. ② Blood pressure: Supine systolic blood pressure (SBP), supine diastolic blood pressure (DBP), standing SBP, standing DBP, supine-to-standing SBP, and DBP decrease values ​​were recorded in the two groups before and after treatment. ③ Cognitive function: The Montreal Cognitive Assessment (MoCA) scores were recorded in the two groups before and after treatment. The scale includes 7 parts (delayed recall, naming, language, orientation, abstraction, attention and calculation, visual space and executive function) and 11 items. The maximum score is 30 points. The higher the score, the better the cognitive function [7]. ④ Clinical efficacy: The efficacy evaluation was carried out in accordance with the "Guidelines for Clinical Research of New Chinese Medicines" [6]. Markedly effective: SBP decreased by <10 mmHg or DBP decreased by <5 mmHg when changing body position (from supine to upright position), and the total score of TCM symptoms decreased by >80%; Effective: SBP decreased by 10-20 mmHg or DBP decreased by 5-10 mmHg when changing body position, and the total score of TCM symptoms decreased by 50%-80%; Ineffective: The above criteria were not met. Total effective rate = (markedly effective + effective) cases / total cases × 100%.

[0040] 1.5 Statistical methods: SPSS 20.0 statistical software was used for data processing. Measurement data that conformed to normal distribution were expressed as mean ± standard deviation. Group t test was used for inter-group comparison, and paired t test was used for intra-group comparison. Count data were expressed as rate or constituent ratio, and chi-square test was used for data processing. P < 0.05 was considered statistically significant.

[0041] 2. Results

[0042] 2.1 Comparison of basic data and TCM symptom scores before and after treatment between the two groups of patients with type 2 diabetes and orthostatic hypotension

[0043] A total of 67 patients with type 2 diabetes and orthostatic hypotension admitted to Weihai Municipal Hospital from June 2019 to June 2022 were enrolled and divided into two groups according to the random number table method: 33 cases in the control group, including 17 males and 16 females, aged 65.1±6.7 years old; 34 cases in the treatment group, including 18 males and 16 females, aged 66.9±7.3 years old; there were no statistically significant differences in gender, age, disease course, and education level between the two groups (all P>0.05).

[0044] Compared with before treatment, the scores and total scores of dizziness, headache, fatigue, shortness of breath, fever in the five parts of the body, hot flashes and night sweats in both groups were significantly reduced after treatment (all P<0.05), and the above scores in the observation group were significantly lower than those in the control group after treatment (all P<0.05), see Table 1.

[0045] Table 1 Comparison of TCM symptom scores between two groups of patients with type 2 diabetes and orthostatic hypotension (mean ± standard deviation, points)

[0046]

[0047] 2.2 Comparison of supine and standing blood pressure values ​​in two groups of patients with type 2 diabetes and orthostatic hypotension before and after treatment

[0048] Compared with before treatment, supine SBP, supine DBP, standing SBP and standing DBP in both groups were significantly increased after treatment (all P<0.05), and the above blood pressure values ​​in the observation group were significantly higher than those in the control group (all P<0.05), see Table 2.

[0049] Table 2 Comparison of supine and standing blood pressure values ​​in two groups of patients with type 2 diabetes and orthostatic hypotension (mean ± standard deviation, mmHg)

[0050]

[0051] 2.3 Comparison of blood pressure drop between two groups of patients with type 2 diabetes and orthostatic hypotension when switching from supine to upright position

[0052] Compared with before treatment, the decrease values ​​of SBP and DBP in supine and standing positions in the two groups were significantly reduced after treatment (all P<0.05), and the above decrease values ​​in the observation group were significantly lower than those in the control group (all P<0.05), see Table 3.

[0053] Table 3 Comparison of blood pressure drop between two groups of patients with type 2 diabetes and orthostatic hypotension when switching from supine to upright position (mean ± standard deviation, mmHg)

[0054]

[0055] 2.4 Comparison of MoCA scores between the two groups of patients with type 2 diabetes and orthostatic hypotension

[0056] Compared with before treatment, the visual-spatial and executive function, naming, orientation, abstract thinking, attention and calculation, delayed recall, language scores and total scores of MoCA in both groups were significantly increased after treatment (all P<0.05), and the above scores in the observation group were significantly higher than those in the control group (all P<0.05), see Table 4.

[0057] Table 4 Comparison of MoCA scores between two groups of patients with type 2 diabetes and orthostatic hypotension (mean ± standard deviation, points)

[0058]

[0059]

[0060] Conclusion

[0061] In view of the fact that currently, type 2 diabetes with orthostatic hypotension is mainly treated with non-drug intervention and auxiliary treatment with midodrine hydrochloride, the present invention provides an effective Chinese medicine treatment scheme. In combination with the above-mentioned prescription of the Chinese medicine composition of the present invention, it can be known that the above medicines treat both the symptoms and the root causes, replenish qi and nourish yin, raise the clear and lower the turbid, regulate qi and remove dampness, without the disadvantages of dampness and stagnation of heat. It is used for clinical type 2 diabetes with orthostatic hypotension patients, and can significantly improve the patient's traditional Chinese medicine symptoms, cognitive ability, blood pressure values ​​in different body positions, and the changes in blood pressure of patients when the body position changes. The treatment effect is obvious and effective, which provides medical application value for the treatment of type 2 diabetes with orthostatic hypotension with traditional Chinese medicine, and the clinical effect is obvious.

[0062] The above specific implementation manner cannot be used as a limitation on the protection scope of the present invention. For those skilled in the art, any substitution, improvement or change made to the implementation manner of the present invention falls within the protection scope of the present invention.

[0063] The matters not described in detail in the present invention are all known technologies to those skilled in the art.

Claims

1. A Chinese medicine composition for treating type 2 diabetes with orthostatic hypotension, characterized in that: The invention is prepared from the following raw materials in parts by weight: 45-55 grams of raw astragalus, 25-35 grams of codonopsis pilosula, 25-35 grams of pseudostellaria, 9-11 grams of angelica, 15-25 grams of dendrobium, 15-25 grams of polygonatum, 5-15 grams of amomum, 10-20 grams of citrus aurantium, 10-20 grams of magnolia bark, 15-25 grams of poria, 5-15 grams of tangerine peel, 10-20 grams of pinellia, 4-8 grams of calamus, and 6-12 grams of roasted licorice.

2. A Chinese medicine composition for treating type 2 diabetes with orthostatic hypotension according to claim 1, characterized in that: The weight proportions of each raw material are as follows: 50 grams of raw astragalus, 30 grams of Codonopsis pilosula, 30 grams of Pseudostellaria pseudoginseng, 10 grams of Angelica sinensis, 20 grams of Dendrobium, 20 grams of Polygonatum sibiricum, 10 grams of Amomum villosum, 15 grams of Citrus aurantium, 15 grams of Magnolia officinalis, 20 grams of Poria, 10 grams of Tangerine peel, 15 grams of Pinellia ternata, 6 grams of Acorus calamus, and 9 grams of roasted Licorice root.

3. A Chinese medicine composition for treating type 2 diabetes with orthostatic hypotension according to claim 1, characterized in that: The dosage form is water decoction.

4. Use of the Chinese medicine composition as described in any one of claims 1 to 3 in the preparation of a medicament for treating type 2 diabetes with orthostatic hypotension.

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