A food-medicine composition for improving vascular dementia, its preparation method and application.

Abstract

This invention provides a medicinal and edible homologous composition for improving vascular dementia, its preparation method, and its application. The composition comprises the following parts by weight of raw materials and fructooligosaccharides: 80-120 parts of steamed Polygonatum sibiricum, 50-70 parts of mulberry, 50-70 parts of wolfberry, 30-50 parts of Poria cocos, 30-50 parts of Astragalus membranaceus, 30-50 parts of donkey-hide gelatin, and 30-50 parts of Codonopsis pilosula; the weight ratio of fructooligosaccharides to the extract obtained from the raw materials is (1.5-3):1. The raw materials used in this invention are all medicinal and edible homologous substances, safe and non-toxic, and can be taken long-term as a functional food. After process optimization, it has a good taste, sweet but not greasy, and high patient compliance. Animal experiments have confirmed that it can significantly improve the learning and memory abilities of rats with vascular dementia. It has the advantages of simple formulation, stable process, definite efficacy, convenient administration, and wide applicability, and has important clinical significance and good market application prospects.

Description

Technical Field

[0001] This invention belongs to the field of food and medicine homology technology, specifically relating to a food and medicine homology composition for improving vascular dementia, its preparation method and application. Background Technology

[0002] Vascular dementia (VaD) is a clinical syndrome caused by cerebrovascular diseases such as cerebral infarction and cerebral hemorrhage, leading to ischemic and hypoxic damage to brain tissue and subsequently causing severe cognitive decline. It is the second most common type of dementia after Alzheimer's disease, accounting for approximately 20% of dementia cases in the elderly. Traditional Chinese medicine theory considers the core pathogenesis of vascular dementia to be kidney deficiency and marrow depletion, along with phlegm and blood stasis.

[0003] Rehmannia Decoction, originating from the Jin Dynasty text *Huangdi Neijing Suwen Xuanming Lunfang*, is composed of 12 herbs including Rehmannia glutinosa (processed), Cornus officinalis, Cistanche deserticola, Morinda officinalis, Acorus tatarinowii, Polygala tenuifolia, and Poria cocos. It nourishes kidney yin, tonifies kidney yang, resolves phlegm, and opens the orifices, effectively addressing the pathogenesis of vascular dementia involving kidney deficiency and phlegm stasis. Therefore, it is widely used clinically in the treatment of vascular dementia. Modern research shows that Rehmannia Decoction exerts neuroprotective effects through multiple targets, inhibiting oxidative stress, reducing neuronal damage, promoting cerebral angiogenesis, improving cerebral blood flow, inhibiting apoptosis of neurons in the CA1 region of the hippocampus, reducing neuroinflammation, and regulating cholinergic system function. Clinical studies have confirmed that Rehmannia Decoction, used alone or in combination with donepezil and other Western medicines, can significantly improve the condition of patients with vascular dementia, with a higher overall effective rate than conventional Western medicine treatment.

[0004] However, existing Rehmannia Decoction preparations are mainly decoctions, which have drawbacks such as inconvenience in preparation, poor taste, and low patient compliance. Furthermore, Rehmannia Decoction consists of 12 herbs, which is numerous and makes the preparation process relatively complex, posing significant challenges to quality control. Therefore, developing a simplified, convenient, and highly acceptable combination of medicinal and edible herbs for improving vascular dementia has important clinical significance. Summary of the Invention

[0005] The technical problem that this invention aims to solve is to provide a food-medicine homology composition for improving vascular dementia, its preparation method, and its application, thereby enhancing the therapeutic effect of vascular dementia.

[0006] To achieve the above objectives, the technical solution of the present invention is implemented as follows: Based on one aspect of the present invention, a food-medicine composition for improving vascular dementia is provided, comprising the following parts by weight of active pharmaceutical ingredient and fructooligosaccharides: Steamed Polygonatum sibiricum 80-120 parts, mulberry 50-70 parts, wolfberry 50-70 parts, Poria cocos 30-50 parts, Astragalus membranaceus 30-50 parts, donkey-hide gelatin 30-50 parts, Codonopsis pilosula 30-50 parts; The weight ratio of the oligofructose to the extract obtained from the raw drug is (1.5-3):1.

[0007] In one embodiment, the food-medicine homology composition comprises the following parts by weight of active pharmaceutical ingredient and fructooligosaccharides: 100 parts of steamed Polygonatum sibiricum, 60 parts of mulberry, 60 parts of wolfberry, 40 parts of Poria cocos, 40 parts of Astragalus membranaceus, 40 parts of donkey-hide gelatin, and 40 parts of Codonopsis pilosula.

[0008] In one embodiment, the weight ratio of the oligofructose to the extract obtained from the raw drug is (1.5-2.5):1.

[0009] In one embodiment, the weight ratio of the fructooligosaccharide to the extract is 2:1.

[0010] Based on another aspect of the present invention, a method for preparing a medicinal and edible composition for improving vascular dementia as described in any of the preceding claims is provided, comprising the following steps: S1: Weigh out the following ingredients by weight: steamed Polygonatum sibiricum, mulberry, wolfberry, Poria cocos, Astragalus membranaceus, donkey-hide gelatin, and Codonopsis pilosula. Add water and decoct twice. For the first decoction, add 8 to 12 times the amount of water and decoct for 0.5 to 2 hours. Filter the decoction. For the second decoction, add 6 to 10 times the amount of water and decoct for 0.5 to 2 hours. Filter the decoction and combine the filtrates. S2: Concentrate the combined filtrate into an extract, centrifuge and set aside. The concentration temperature is 60-80℃, the vacuum degree is -0.07 to -0.09MPa, and the density of the extract is 1.2-1.4g / ml. S3: Weigh the fructooligosaccharide syrup according to the weight of the extract obtained in step S2, mix the fructooligosaccharide syrup and the extract at a weight ratio of (1.5~3):1, heat, stir evenly, and cool to obtain the final product.

[0011] In one embodiment, in step S1, 10 times the amount of water is added for the first time and the mixture is simmered for 1 hour; then 8 times the amount of water is added for the second time and the mixture is simmered for 1 hour.

[0012] In one embodiment, the temperature for the two decocting processes in step S1 is set at 95±5℃.

[0013] In one embodiment, the concentration temperature in step S2 is 70°C.

[0014] In one embodiment, the extract is concentrated to a density of 1.3 g / ml in step S2.

[0015] Based on another aspect of the present invention, the use of the food-medicine composition for improving vascular dementia as described in any of the preceding claims in the preparation of a medicament for improving vascular dementia is provided.

[0016] Compared with existing technologies, the medicinal and edible composition of the present invention for improving vascular dementia uses steamed Polygonatum as the principal ingredient, combined with mulberry and wolfberry to nourish kidney yin, astragalus, codonopsis, and poria to invigorate the spleen and replenish qi, and donkey-hide gelatin to nourish blood. The entire formula works synergistically to nourish the kidneys and replenish essence, replenish qi and blood, and invigorate the spleen and promote digestion, thus addressing the pathogenesis of vascular dementia characterized by kidney deficiency and marrow depletion, and phlegm stagnation. Furthermore, all raw materials used in the composition of the present invention are medicinal and edible substances. Polygonatum, mulberry, wolfberry, poria, astragalus, donkey-hide gelatin, and codonopsis are all listed in the Pharmacopoeia of the People's Republic of China and are included in the list of medicinal and edible substances published by the National Health Commission or are medicinal materials that can be used in health foods. Therefore, the composition of the present invention combines the safety of food with the efficacy of medicine, and can be taken as a functional food for long-term use. It is suitable for daily conditioning of patients with vascular dementia and high-risk groups of cognitive decline, with no obvious toxic side effects and is safe to take.

[0017] Compared to existing formulas for treating vascular dementia, this invention consists of only seven raw materials, resulting in a simplified formulation, simpler preparation process, reduced quality control difficulty, and higher patient compliance. This invention uses fructooligosaccharide syrup as an excipient. Fructooligosaccharides are not only a high-quality sweetener but also possess prebiotic functions, regulating intestinal flora without causing drastic fluctuations in blood sugar, making them suitable for a wider range of people, including those with hypertension, hyperlipidemia, and hyperglycemia. Through systematic single-factor and orthogonal experiments, this invention comprehensively optimized key extraction process parameters such as the ratio of raw materials, types and amounts of excipients, extraction times, water volume, decoction time, and concentration temperature. Based on the seven raw materials—steamed Polygonatum sibiricum, mulberry, wolfberry, Poria cocos, Astragalus membranaceus, donkey-hide gelatin, and Codonopsis pilosula—the optimal weight ratio of 100:60:60:40:40:40:40 was selected using the taste, color, and yield of the extract as evaluation indicators. The process parameters are clear, highly operable, and ensure product quality stability and batch-to-batch consistency. This invention relates to a medicinal paste formulation with a pleasant taste after process optimization. The formula has been adjusted for optimal taste, resulting in a sweet but not cloying flavor with a slightly sour aftertaste, while retaining the original medicinal aroma of the extract. Through excipient selection, fructooligosaccharide syrup has been chosen as an excipient, ensuring a moderate sweetness and delicate texture. Compared to commercially available traditional medicinal pastes such as Gu Yuan Gao and Ba Zhen Gao, this invention has a very mild bitterness, making it more acceptable to middle-aged and elderly individuals and resulting in high patient compliance. The paste is in a semi-liquid or frozen form, making it convenient to take, easy to store and carry, and suitable for long-term use by patients with chronic diseases.

[0018] In summary, this invention provides a food-medicine homology composition with a simplified formulation, stable process, definite efficacy, convenient administration, and wide applicability. It can be used to improve vascular dementia and has significant clinical significance and good market application prospects. Detailed Implementation

[0019] To make the objectives, technical solutions, and advantages of this application clearer, the following detailed description is provided in conjunction with embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the scope of this application.

[0020] Example 1 This embodiment provides a Polygonatum rhizome paste formula for improving vascular dementia, which is composed of the following raw materials and fructooligosaccharides in parts by weight: 100g of steamed Polygonatum sibiricum, 60g of mulberry, 60g of wolfberry, 40g of Poria cocos, 40g of Astragalus membranaceus, 40g of donkey-hide gelatin, and 40g of Codonopsis pilosula; the weight ratio of fructooligosaccharides to the extract obtained from the raw materials is 2:1.

[0021] The Polygonatum extract formula for improving vascular dementia in this embodiment is prepared by the following method: S1: Weigh out the following ingredients according to the above weight proportions: steamed Polygonatum sibiricum, mulberry, wolfberry, Poria cocos, Astragalus membranaceus, donkey-hide gelatin, and Codonopsis pilosula. Add water and decoct twice. For the first decoction, add 10 times the amount of water and decoct at 95±5 degrees Celsius for 1 hour. Filter the decoction. For the second decoction, add 8 times the amount of water and decoct at 95±5 degrees Celsius for 1 hour. Filter the decoction and combine the filtrates. S2: Concentrate the combined filtrate into an extract, centrifuge and set aside. The concentration temperature is 70℃, the vacuum degree is -0.07~-0.09MPa, and the density of the extract is 1.3g / ml. S3: Weigh the fructooligosaccharide syrup according to the weight of the extract obtained in step S2, mix the fructooligosaccharide syrup and the extract at a weight ratio of 2:1, heat, stir evenly, and cool to obtain the final product.

[0022] Example 1: Experimental Preparation Process of Polygonatum Ointment 1. Experimental Objective The formulation, taste, excipients, and manufacturing process of Polygonatum odoratum paste were studied, and the relevant process parameters were confirmed.

[0023] 2. Experimental Instruments and Materials Rotary evaporator (LCJ-RE-5000, Shanghai Lichen Bangxi Instrument Technology Co., Ltd.), extraction vessel, sieve, balance (XY600-2C, Changzhou Lucky Electronic Technology Co., Ltd.) 3. Experimental content and results 3.1 Taste Test of Extracts from Single Raw Materials 3.1.1 Extraction process (1) Polygonatum: Take 200g of Polygonatum, add water and decoct twice. Add 10 times the amount of water for the first decoction, decoct twice, and filter. Add 8 times the amount of water for the second decoction, filter, combine the filtrates, and concentrate to extract.

[0024] (2) Goji berries: Take 200g of goji berries, add water and decoct twice. For the first decoction, add 10 times the amount of water and decoct twice with a slight boil, then filter. For the second decoction, add 8 times the amount of water, filter, combine the filtrates, and concentrate to extract.

[0025] (3) Mulberry: Take 200g of mulberry, add water and decoct twice. For the first decoction, add 10 times the amount of water and boil twice. Filter the decoction. For the second decoction, add 8 times the amount of water and filter the decoction. Combine the filtrates and concentrate them into an extract.

[0026] (4) Poria: Take 200g of Poria, add water and decoct twice. For the first decoction, add 10 times the amount of water and boil twice. Filter the decoction. For the second decoction, add 8 times the amount of water and filter the decoction. Combine the filtrates and concentrate them into an extract.

[0027] (5) Astragalus: Take 200g of raspberry, add water and decoct twice. For the first decoction, add 10 times the amount of water and boil twice. Filter the decoction. For the second decoction, add 8 times the amount of water and filter the decoction. Combine the filtrates and concentrate them into an extract.

[0028] (6) Donkey-hide gelatin: Take 200g of donkey-hide gelatin, add water and decoct twice. For the first decoction, add 10 times the amount of water and decoct twice with a slight boil. Filter the solution. For the second decoction, add 8 times the amount of water, filter the solution, combine the filtrates, and concentrate the solution into an extract.

[0029] (7) Codonopsis pilosula: Take 200g of Codonopsis pilosula, add water and decoct twice. For the first decoction, add 10 times the amount of water and decoct twice with a slight boil, then filter. For the second decoction, add 8 times the amount of water, filter, combine the filtrates, and concentrate to extract.

[0030] 3.1.2 Extraction Results Each raw material was extracted and concentrated according to the extraction process described in "3.1.1", and the yield, color, taste, and density of the corresponding extracts were evaluated. The results are shown in Table 1.

[0031] Table 1 - Taste of Single-Flavor Raw Material Extracts

[0032] 3.2 Evaluation of Formula Composition and Taste 3.2.1 Formulation and Proportioning Design To obtain a Huangjing (Polygonatum sibiricum) paste formula that is rationally formulated, has a good taste, and is suitable for long-term use, different formulation schemes were designed and comprehensively screened based on the fixed types of raw materials, taking the weight ratio of the raw materials as a factor, and using the taste, color, and yield of the extract as evaluation indicators, to determine the optimal ratio range. The appropriate weight of extract was taken according to the different formula requirements, heated and stirred evenly, and then cooled to obtain the final product. The formula ratios are shown in Table 2.

[0033] Table 2 - Formulas for Polygonatum Ointment

[0034] 3.2.2 Taste Test Results of the Formula Ten people were randomly selected to test the taste and color of samples A, B, C, D, E, F, and G, and voted to select the formula with the best taste. The results are shown in Table 3.

[0035] Table 3 - Results of Huangjing Ointment Formula

[0036] The results showed that option G was the most popular and had the best taste. The final ingredient formula determined through conversion was 100g of steamed Polygonatum sibiricum, 60g of mulberry, 60g of wolfberry, 40g of Poria cocos, 40g of Astragalus membranaceus, 40g of donkey-hide gelatin, and 40g of Codonopsis pilosula.

[0037] 3.3 Formulation and Process Optimization 3.3.1 Extraction and Investigation Option A: Take 100g of steamed Polygonatum sibiricum, 60g of mulberry, 60g of wolfberry, 40g of Poria cocos, 40g of Astragalus membranaceus, 40g of donkey-hide gelatin, and 40g of Codonopsis pilosula. Add water and decoct twice. For the first decoction, add 10 times the amount of water and decoct for 1 hour, then filter. For the second decoction, add 8 times the amount of water and decoct for 1 hour, then filter. Combine the filtrates.

[0038] Option B: Take 100g of steamed Polygonatum sibiricum, 60g of mulberry, 60g of wolfberry, 40g of Poria cocos, 40g of Astragalus membranaceus, 40g of donkey-hide gelatin, and 40g of Codonopsis pilosula. Add water and decoct twice. For the first decoction, add 12 times the amount of water and decoct for 1 hour, then filter. For the second decoction, add 10 times the amount of water and decoct for 1 hour, then filter. Combine the filtrates.

[0039] Option C: Take 100g of steamed Polygonatum sibiricum, 60g of mulberry, 60g of wolfberry, 40g of Poria cocos, 40g of Astragalus membranaceus, 40g of donkey-hide gelatin, and 40g of Codonopsis pilosula. Add water and decoct three times. For the first decoction, add 10 times the amount of water and decoct for 1 hour, then filter. For the second decoction, add 8 times the amount of water and decoct for 1 hour, then filter. For the third decoction, add 6 times the amount of water and decoct for 1 hour, then filter. Combine the filtrates.

[0040] 3.3.2 Extraction Results The yield of the extracted samples was tested, and the results are shown in Table 4.

[0041] Table 4 - Extraction Results

[0042] The data shows that the yield of extract from schemes A, B, and C is not significantly different. To save costs, scheme A is tentatively chosen. Therefore, the extraction process for Polygonatum extract is to decoct twice with water. For the first decoction, add 10 times the amount of water, decoct for 1 hour, and filter. For the second decoction, add 8 times the amount of water, decoct for 1 hour, filter, and combine the filtrates.

[0043] 3.4 Concentrated Investigation Take 100g of steamed Polygonatum sibiricum, 60g of mulberry, 60g of wolfberry, 40g of Poria cocos, 40g of Astragalus membranaceus, 40g of donkey-hide gelatin, and 40g of Codonopsis pilosula. Add water and decoct twice. For the first decoction, add 10 times the amount of water and decoct for 1 hour, then filter. For the second decoction, add 8 times the amount of water and decoct for 1 hour, then filter. Combine the filtrates, cool to room temperature, and divide into three equal portions. Option A: Take the above extract and concentrate it at 50 degrees Celsius to a density of about 1.3% (vacuum degree: -0.07 to -0.09 MPa).

[0044] Option B: Take the above extract and concentrate it at 60 degrees Celsius to a density of about 1.3% (vacuum degree: -0.07 to -0.09 MPa).

[0045] Option C: Take the above extract and concentrate it at 70 degrees Celsius to a density of about 1.3% (vacuum degree: -0.07 to -0.09 MPa).

[0046] 3.4.1 Results of Concentration Temperature Study Based on the above experiments, the adhesion of the extract to the wall was investigated during the concentration process. The results are shown in Table 5.

[0047] Table 5 - Results of Concentration Temperature and Vacuum Degree Testing

[0048] The data shows that the yield of the extract is not significantly different between schemes A, B, and C, so scheme C is tentatively chosen. Therefore, the concentration temperature of the Polygonatum extract formula is 70 degrees Celsius, and the vacuum degree is -0.07 to -0.09 MPa.

[0049] 3.5 Examination of excipients 3.5.1 Experimental Design for Different Excipients Take the extract from Scheme A in item “3.3.1”, concentrate it to a paste (density of 1.3g / ml), add the excipient aqueous solution (1:1) according to the different schemes below, heat and stir evenly, cool, and the product is obtained.

[0050] Option A: Take 10g of extract, add 5g of peppermint syrup, heat and stir until well mixed.

[0051] Option B: Take 10g of extract, add 5g of fructooligosaccharide syrup, heat and stir until evenly mixed.

[0052] Option C: Take 10g of extract, add 5g of xylitol syrup, heat and stir until well mixed.

[0053] Option D: Take 10g of extract, add 5g of xylitol syrup, heat and stir until well mixed.

[0054] 3.5.2 Taste Test and Results Ten people were randomly selected to test the taste and color of recipes A, B, C, and D, and voted on them. The votes were tallied to select the recipe with the best taste. The results are shown in Table 6. Table 6 - Results of taste tests for different additives

[0055] The results showed that fructooligosaccharide syrup had a better taste and was more suitable for people with the "three highs" (hypertension, hyperglycemia, and hyperlipidemia). Therefore, the excipient for the Polygonatum sibiricum paste formula was tentatively set as fructooligosaccharide syrup.

[0056] 3.6 Study on the Amount of Additives 3.6.1 Examination of the Amount of Additives Take the extract from Scheme A in item “3.3.1”, concentrate it to a paste (density of 1.3 g / ml), add the excipient aqueous solution (1:1) according to the excipient amounts of the following different schemes, heat and stir evenly, cool, and the product is obtained.

[0057] Option A: Take 9g of Polygonatum extract, add 1g of fructooligosaccharide syrup, heat and stir until well mixed.

[0058] Option B: Take 9g of Polygonatum extract, add 2g of fructooligosaccharide syrup, heat and stir until well mixed.

[0059] Option C: Take 9g of Polygonatum extract, add 3g of fructooligosaccharide syrup, heat and stir until well mixed.

[0060] Option D: Take 8g of Polygonatum extract, add 4g of fructooligosaccharide syrup, heat and stir until well mixed.

[0061] Option E: Take 8g of Polygonatum extract, add 5g of fructooligosaccharide syrup, heat and stir until well mixed.

[0062] Option F: Take 8g of Polygonatum extract, add 6g of fructooligosaccharide syrup, heat and stir until well mixed.

[0063] 3.6.2 Taste Test and Results Ten randomly selected individuals conducted taste and color tests on recipes A, B, C, D, E, and F, and voted on them. The votes were tallied to select the recipe with the best taste. The results are shown in Table 7. Table 7 - Results of the Investigation on the Amount of Additives

[0064] Experimental results show that Scheme D has a better taste, sweet but not cloying, and retains the original medicinal aroma of the extract. However, considering the cost, Scheme C is tentatively chosen. Therefore, the excipient addition amount for the Polygonatum extract formula is: Polygonatum extract formula: fructooligosaccharide syrup weight ratio is 1:2.

[0065] 4. Experiment Summary Based on the above research, the relevant process parameters for the Polygonatum odoratum paste formula were finally determined as follows: (1) Prescription: 100g of steamed Polygonatum, 60g of mulberry, 60g of wolfberry, 40g of Poria cocos, 40g of Astragalus membranaceus, 40g of donkey-hide gelatin, and 40g of Codonopsis pilosula. Add fructooligosaccharide syrup (the weight ratio of Polygonatum paste to fructooligosaccharide syrup is 1:2), heat and mix well to make 1000g of Polygonatum paste.

[0066] (2) Extraction process: Add water and decoct twice. Add 10 times the amount of water for the first decoction and decoct twice, then filter. Add 8 times the amount of water for the second decoction and filter. Combine the filtrates and concentrate (temperature: 70℃; vacuum: -0.07~-0.09 Mpa) to obtain an extract (density of 1.3mg / ml). Prepare about 350g of thick extract.

[0067] (3) Mixing process: Take the extract and mix it with the fructooligosaccharide syrup in a ratio of (1:2) and heat and stir until uniform.

[0068] (4) Preparation: Weigh out the prescribed amounts of Polygonatum sibiricum, mulberry, wolfberry, Poria cocos, Astragalus membranaceus, donkey-hide gelatin, and Codonopsis pilosula, add water and decoct twice. For the first decoction, add 10 times the amount of water, decoct at 95±5 degrees Celsius for 1 hour, and filter. For the second decoction, add 8 times the amount of water, decoct at 95±5 degrees Celsius for 1 hour, filter, combine the extracts, concentrate to a paste (density of about 1.3 g / ml), and centrifuge for later use. Make about 350 g of thick paste, add about 700 g of fructooligosaccharide syrup, heat, stir evenly, and cool to obtain about 1000 g of paste.

[0069] II. Example 1: Evaluation Experiment on the Effect of Polygonatum Ointment on Learning and Memory Ability of a Rat Model of Vascular Dementia 1. Experimental Materials 1.1 Laboratory Animals Seventy SPF-grade male SD rats, weighing 250±20g, were housed at a temperature of 22±2℃ and humidity of 50±10%, with a 12h light / 12h dark cycle and free access to food and water. Experiments began after one week of acclimatization.

[0070] 1.2 Drugs and Reagents Polygonatum extract formula: Prepared according to the method in Example 1 of this invention (steamed Polygonatum 100g, mulberry 60g, wolfberry 60g, Poria cocos 40g, Astragalus membranaceus 40g, donkey-hide gelatin 40g, Codonopsis pilosula 40g, add water and decoct twice. For the first decoction, add 10 times the amount of water and decoct at 95±5℃ for 1 hour, then filter. For the second decoction, add 8 times the amount of water and decoct at 95±5℃ for 1 hour, then filter. Combine the filtrates and concentrate to a density of 1.3g / ml. Mix with fructooligosaccharide syrup at a ratio of 1:2. Before use, dilute with distilled water to the required concentration.

[0071] Positive control drug: Donepezil hydrochloride tablets, ground into a fine powder before use, and prepared into a 0.5 mg / ml suspension with distilled water.

[0072] Sodium pentobarbital: Prepare a 1% solution with physiological saline.

[0073] Chloral hydrate: Prepare a 10% solution with physiological saline.

[0074] 1.3 Main Instruments Morris water maze video analysis system, upright microscope, paraffin microtome, low-temperature high-speed centrifuge, microplate reader, and electric thermostatic water bath.

[0075] 2. Experimental Methods 2.1 Animal grouping Seventy SD rats were acclimatized for one week and then randomly divided into seven groups of 10 rats each:

[0076] Note: Based on the recommended human clinical dosage (30g of the paste / 60kg body weight per day) converted according to body surface area, the equivalent dose for rats is approximately 3.1g / kg. This study set up three dosage groups: low (1g / kg, approximately 1 / 3 of the equivalent dose), medium (2g / kg, approximately 2 / 3 of the equivalent dose), and high (4g / kg, approximately 1.3 times the equivalent dose) to observe the dose-effect relationship. The Rehmannia Decoction group served as a positive control for traditional Chinese medicine, used to compare the efficacy difference between the Polygonatum paste of Example 1 of this invention and the classic formula Rehmannia Decoction. Rehmannia Decoction group: The Rehmannia Decoction prescription recorded in "Shengji Zonglu" (15g each of Rehmannia glutinosa, Cornus officinalis, Cistanche deserticola, Morinda officinalis, Aconitum carmichaelii, Cinnamomum cassia, Dendrobium nobile, Ophiopogon japonicus, Schisandra chinensis, Acorus tatarinowii, Polygala tenuifolia, and Poria cocos) was decocted twice with water, the filtrates were combined, concentrated to the required concentration, and stored at 4℃ for later use.

[0077] 2.2 Establishment of a rat model of vascular dementia A rat model of chronic cerebral hypoperfusion vascular dementia induced by bilateral common carotid artery permanent ligation was established by referring to the two-vessel occlusion method (2-VO method) reported in the literature.

[0078] Detailed operation steps: Rats were fasted for 12 hours before surgery but given free access to water.

[0079] Rats were anesthetized by intraperitoneal injection of 10% chloral hydrate (3 ml / kg).

[0080] The rat was fixed in a supine position on the operating table, and the neck was prepared and disinfected.

[0081] Make a longitudinal incision of about 2cm along the midline of the neck, and separate the subcutaneous tissue and muscles layer by layer to expose the bilateral common carotid arteries.

[0082] Permanently ligate both common carotid arteries with 4-0 silk sutures, taking care to avoid the vagus nerve and trachea.

[0083] The incision was sutured layer by layer, and the area was disinfected.

[0084] In the sham surgery group, only the bilateral common carotid arteries were separated without ligation; the rest of the procedures were the same.

[0085] Postoperatively, administer intramuscular injections of penicillin (80,000 U / vial) for three consecutive days to prevent infection.

[0086] Successful model criteria: Seven days after surgery, two rats were randomly selected from the model group, their heads were severed and their brains were removed, and TTC staining was used to observe the cerebral ischemia. At the same time, a water maze pre-test was conducted. Compared with the sham-operated group, the escape latency of the model group was significantly prolonged (P<0.05), which was considered a successful model.

[0087] 2.3 Dosing regimen Drug administration began on the 8th day after the modeling surgery, with all groups receiving administration by gavage once daily for 28 consecutive days. The administration volume was 10 ml / kg. The sham surgery group and the model control group received an equal volume of distilled water by gavage.

[0088] 2.4 Morris Water Maze Experiment Water maze navigation training was conducted from day 22 to day 27 after drug administration, and space exploration experiments were conducted on day 28.

[0089] Water maze apparatus: A circular pool (150cm in diameter, 60cm in height), with a water temperature of 22±2℃, filled with turbid water (with an appropriate amount of ink or milk powder added to make the underwater platform invisible to the rats). The hidden platform (10cm in diameter) is located approximately 1cm underwater, in the center of quadrant II.

[0090] Orientation and navigation training (days 22-27): Each day, rats were placed in the water facing the pool wall from four different quadrants (I, II, III, IV), and the time it took for the rat to find the platform (escape latency) was recorded. Each training session lasted a maximum of 90 seconds. If the rat failed to find the platform within 90 seconds, it was guided to the platform and remained there for 15 seconds; the escape latency was recorded as 90 seconds. Training was conducted four times a day for six consecutive days, and the average of the four training sessions each day was taken as the escape latency for that day.

[0091] Space exploration experiment (day 28): Remove the underwater platform and place the rats into the water from the first quadrant (opposite side of the original platform) facing the pool wall. Record the number of times the rats cross the original platform position within 90 seconds and the time spent in the first quadrant (second quadrant) where the original platform was located.

[0092] 2.5 Brain tissue sampling and processing After the behavioral experiments, five rats were randomly selected from each group and deeply anesthetized by intraperitoneal injection of 10% chloral hydrate (3 ml / kg). The heart was exposed by thoracotomy, and the ascending aorta was accessed via left ventricle puncture. 200 ml of pre-cooled physiological saline was rapidly perfused, followed by 200 ml of 4% paraformaldehyde (pH 7.4) for internal fixation. The rats were decapitated and the brain tissue was placed in 4% paraformaldehyde and fixed for 24 hours. The tissue was then routinely dehydrated, embedded in paraffin, and sectioned (5 μm thick) for HE staining and Nissl staining.

[0093] Five rats from each group were then anesthetized, decapitated, and had their brains removed. The hippocampus and cortical tissues were quickly separated on ice and stored at -80°C for biochemical index detection.

[0094] 2.6 Histopathological observation of the CA1 region of the hippocampus HE staining: Paraffin sections were dewaxed to water, stained with hematoxylin for 5 min, differentiated with hydrochloric acid and ethanol for 3 s, stained with eosin for 3 min, dehydrated with graded ethanol, cleared with xylene, and mounted with neutral resin. The morphology of neurons in the CA1 region of the hippocampus was observed under a light microscope, including neuronal arrangement, cell morphology, and nuclear pyknosis.

[0095] Nissl staining: Paraffin sections were dewaxed to water, stained with toluidine blue for 30 min (60℃), separated by 95% ethanol, dehydrated with anhydrous ethanol, cleared with xylene, and mounted with neutral resin. The morphology of Nissl bodies in the CA1 region of the hippocampus was observed under a light microscope, and the number of Nissl body-positive neurons was counted. For each section, three non-overlapping fields of view were randomly selected from the CA1 region of the hippocampus under high magnification (×400), and the number of Nissl body-positive neurons in each field was counted and averaged.

[0096] 2.7 Detection of biochemical indicators in brain tissue Hippocampal tissue stored at -80℃ was weighed and added to pre-cooled physiological saline at a ratio of 1:9 (g / ml). The mixture was homogenized in an ice bath and centrifuged at 3000 rpm for 15 min at 4℃. The supernatant was collected, and the total protein concentration was determined using the BCA method. Then, the following indicators were detected using ELISA or colorimetric methods:

[0097] Acetylcholine (ACh): Rat acetylcholine ELISA kit (E-EL-0081c, Elabscience). Acetylcholinesterase (AChE): Rat acetylcholinesterase ELISA kit (E-EL-R0965, Elabscience). Superoxide dismutase (SOD): Rat superoxide dismutase ELISA kit (E-EL-R1424, Elabscience). Malondialdehyde (MDA): Rat malondialdehyde ELISA kit (E-EL-0060c, Elabscience). Tumor necrosis factor-α (TNF-α): Rat TNF-α ELISA kit (E-EL-R2856, Elabscience). Interleukin-6 (IL-6): Rat IL-6 ELISA kit (E-EL-R0015, Elabscience). All operations were performed according to the kit instructions. The OD values ​​of each well were measured at 450 nm using a Bio-Rad iMark microplate reader, and the concentrations of each indicator were calculated based on the standard curve. The final results are expressed as per milligram of protein ( / mg prot).

[0098] 2.8 Statistical Analysis Experimental data are expressed as mean ± standard deviation ( Data analysis was performed using mean ± standard deviation (±s). One-way ANOVA was used for comparisons among multiple groups, and LSD-t test (when variances are homogeneous) or Games-Howell test (when variances are unequal) was used for pairwise comparisons between groups. A p-value < 0.05 was considered statistically significant.

[0099] 3. Experimental Results 3.1 Comparison of escape latency among different groups of rats The results of the navigation training are shown in Table 8. Compared with the sham-operated group, the escape latency of rats in the model control group was significantly prolonged at all time points (P<0.01), indicating that the vascular dementia model rats have significant learning and memory impairment. Compared with the model control group, the escape latency of rats in the medium and high dose groups of Huangjing Gaofang (Polygonatum sibiricum) was significantly shortened from day 3 of training (P<0.05 or P<0.01), and this was dose-dependent. The escape latency of the high dose group of Huangjing Gaofang on days 5-6 was comparable to that of the positive control group (donepezil) (P>0.05), and there was no statistically significant difference compared with the Dihuang Yinzi (Rehmannia glutinosa) group (P>0.05).

[0100] Table 8 - Comparison of escape latency periods in local navigation training among different groups of rats ( ±s, unit: s, n=10)

[0101] Note: Compared with the sham surgery group, **P<0.01; compared with the model control group, #P<0.05, ##P<0.01.

[0102] 3.2 Comparison of spatial exploration results among different groups of rats The results of the spatial exploration experiment are shown in Table 9. Compared with the sham-operated group, the number of times rats in the model control group crossed the platform and the time spent in the target quadrant were significantly reduced (P<0.01), indicating that the spatial memory ability of the model rats was severely impaired. Compared with the model control group, the number of times rats in the medium and high dose groups of Huangjing Gaofang (Polygonatum sibiricum extract) crossed the platform was significantly increased (P<0.05 or P<0.01), and the time spent in the target quadrant was significantly prolonged (P<0.05 or P<0.01), indicating that it can improve the spatial learning and memory ability of vascular dementia model rats. The high dose group of Huangjing Gaofang was superior to the Rehmannia glutinosa decoction group in terms of the number of times they crossed the platform (P<0.05).

[0103] Table 9 - Comparison of spatial exploration results of rats in each group ( (±s, n=10)

[0104] Note: Compared with the sham surgery group, **P<0.01; compared with the model control group, #P<0.05, ##P<0.01; compared with the Rehmannia Decoction group, *P<0.05.

[0105] 3.3 Histopathological observation of the CA1 region of the hippocampus in each group of rats HE staining results: Observed under a light microscope (×200, ×400): In the sham surgery group, neurons in the CA1 region of the hippocampus were neatly and densely arranged, with cone-shaped cells, large and round nuclei that were lightly stained, clear nucleoli, and normal pericellular spaces. No obvious neuronal damage was observed.

[0106] Model control group: The neurons in the CA1 region of the hippocampus were disordered and sparse, with cell shrinkage, condensed and deeply stained nuclei, and a large number of vacuolar degenerations were visible. The number of neurons was significantly reduced, indicating that chronic cerebral hypoperfusion caused severe damage to neurons in the CA1 region of the hippocampus.

[0107] Positive control group: neurons were more neatly arranged, cell morphology was improved, vacuolar degeneration was reduced, and neuronal damage was significantly reduced.

[0108] Low-dose group of Huangjing ointment: Neuronal damage was reduced and some cell morphology improved, but a small number of shrunken cells were still visible.

[0109] In the medium-dose group of Huangjing ointment: neurons were arranged more neatly, cell morphology was significantly improved, vacuolar degeneration was reduced, and Nissl bodies were more abundant.

[0110] High-dose group of Polygonatum sibiricum paste: neurons are arranged more neatly, cells are morphologically intact, nuclei are clear, vacuolar degeneration is rare, Nissl bodies are abundant, approaching the level of the sham-operated group.

[0111] The Rehmannia Decoction Group showed significantly reduced neuronal damage, more orderly arrangement of neurons, and improved cell morphology.

[0112] Nissl staining results: Nissl bodies are important structures for protein synthesis within neurons, and their number reflects neuronal metabolic activity. As shown in Table 10, compared with the sham-operated group, the number of Nissl body-positive neurons in the CA1 region of the hippocampus of the model control group was significantly reduced (P<0.01). Compared with the model control group, the number of Nissl body-positive neurons in the medium and high dose groups of Huangjing Gaofang (Polygonatum sibiricum extract) was significantly increased (P<0.05 or P<0.01), indicating that it can protect the metabolic activity of neurons. There was no statistically significant difference between the high dose group of Huangjing Gaofang and the Dihuang Yinzi (Rehmannia glutinosa decoction) group (P>0.05).

[0113] Table 10 - Comparison of the number of Nissl body positive neurons in the CA1 region of the hippocampus of rats in each group ( ±s, individuals / field of view, n=5)

[0114] Note: Compared with the sham surgery group, **P<0.01; compared with the model control group, #P<0.05, ##P<0.01.

[0115] 3.4 Comparison of biochemical indicators of hippocampal tissue in different groups of rats As shown in Table 11, compared with the sham-operated group, the hippocampal ACh content of the model control group rats was significantly decreased (P<0.01), AChE activity was significantly increased (P<0.01), SOD activity was significantly decreased (P<0.01), and MDA, TNF-α, and IL-6 content was significantly increased (P<0.01), indicating that the vascular dementia model rats had cholinergic system dysfunction, oxidative stress, and neuroinflammation.

[0116] Compared with the model control group, the medium and high dose groups of Huangjing Gaofang (Polygonatum sibiricum extract) significantly increased ACh content (P<0.05 or P<0.01), decreased AChE activity (P<0.05 or P<0.01), increased SOD activity (P<0.05 or P<0.01), and decreased MDA, TNF-α, and IL-6 content (P<0.05 or P<0.01) in a dose-dependent manner, indicating that it can improve cholinergic system dysfunction, reduce oxidative stress damage, and inhibit neuroinflammatory response in rats with vascular dementia. The high dose group of Huangjing Gaofang was superior to the Dihuang Yinzi (Rehmannia glutinosa decoction) group in increasing ACh and decreasing AChE and TNF-α (P<0.05).

[0117] Table 11 - Comparison of biochemical indicators of hippocampal tissue in rats of different groups ( ±s, n=5)

[0118] Note: Compared with the sham surgery group, **P<0.01; compared with the model control group, #P<0.05, ##P<0.01; compared with the Rehmannia Decoction group, *P<0.05.

[0119] 4. Experimental Conclusions The Polygonatum rhizome paste formula of this invention has a significant therapeutic effect on rats with vascular dementia induced by the two-vessel occlusion method (2-VO method), specifically manifested as follows: Improving learning and memory abilities: The medium and high doses of Polygonatum sibiricum paste significantly shortened the escape latency in orientation navigation training and increased the number of platform crossings and the time spent in the target quadrant in spatial exploration experiments, indicating that it can improve the spatial learning and memory abilities of VaD model rats.

[0120] Protecting neurons in the CA1 region of the hippocampus: HE staining and Nissl staining results showed that Polygonatum rhizome paste can reduce neuronal damage in the CA1 region of the hippocampus, increase the number of Nissl body positive neurons, and protect the metabolic activity of neurons.

[0121] Regulation of cholinergic system function: Polygonatum extract can increase the ACh content in hippocampal tissue, reduce AChE activity, and improve cholinergic system dysfunction in VaD model rats.

[0122] Antioxidant and anti-inflammatory effects: Polygonatum extract can increase SOD activity, reduce MDA content, and alleviate oxidative stress damage; at the same time, it can reduce TNF-α and IL-6 content and inhibit neuroinflammatory response.

[0123] Safety evaluation: Throughout the entire experiment (28 consecutive days of administration), no rats in any of the Huangjing ointment dosage groups experienced death or significant behavioral abnormalities. During the administration period, the weight gain of rats in all groups was normal, and no abnormalities were observed in feeding, drinking, defecation, urination, or general behavior. After the experiment, gross anatomical observation of the major organs (heart, liver, spleen, lungs, and kidneys) of the rats revealed no obvious organic lesions. The above results indicate that the Huangjing ointment of this invention has no significant toxic side effects within the dosage range of 1-4 g / kg / day (equivalent to 0.3-1.3 times the recommended human clinical dose), has good safety, and is suitable for long-term use.

[0124] Under the experimental conditions, the high-dose group of Huangjing paste (4g / kg / d) showed the best effect, and was superior to the classic formula Dihuang decoction group in improving learning and memory ability, increasing ACh content, and reducing AChE activity and TNF-α content. This indicates that the Huangjing paste of the present invention has a good preventive and therapeutic effect on vascular dementia. Moreover, with better efficacy, the formula is simpler than the 12 herbs in Dihuang decoction, the preparation process is simpler, and the patient compliance is higher.

[0125] Those skilled in the art should understand that the discussion of any of the above embodiments is merely exemplary and is not intended to imply that the scope of protection of this application is limited to these examples; within the framework of this application, the technical features of the above embodiments or different embodiments can also be combined, the steps can be implemented in any order, and there are many other variations of different aspects of one or more embodiments of this application as described above, which are not provided in detail for the sake of brevity.

[0126] One or more embodiments in this application are intended to cover all such substitutions, modifications, and variations that fall within the broad scope of this application. Therefore, any omissions, modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of one or more embodiments in this application should be included within the protection scope of this application.

Claims

1. A pharmacological and nutritional composition for improving vascular dementia, the composition comprising, It consists of the following parts by weight of active pharmaceutical ingredient and fructooligosaccharides: Steamed Polygonatum sibiricum 80-120 parts, mulberry 50-70 parts, wolfberry 50-70 parts, Poria cocos 30-50 parts, Astragalus membranaceus 30-50 parts, donkey-hide gelatin 30-50 parts, Codonopsis pilosula 30-50 parts; The weight ratio of the oligofructose to the extract obtained from the raw drug is (1.5-3):

1.

2. The food-medicine composition for improving vascular dementia as described in claim 1, characterized in that, It consists of the following parts by weight of active pharmaceutical ingredient and fructooligosaccharides: 100 parts of steamed Polygonatum sibiricum, 60 parts of mulberry, 60 parts of wolfberry, 40 parts of Poria cocos, 40 parts of Astragalus membranaceus, 40 parts of donkey-hide gelatin, and 40 parts of Codonopsis pilosula.

3. The medicinal and edible composition for improving vascular dementia as described in claim 2, characterized in that, The weight ratio of the oligofructose to the extract obtained from the raw drug is (1.5-2.5):

1.

4. The food-medicine composition for improving vascular dementia as described in claim 2, characterized in that, The weight ratio of the oligofructose to the extract is 2:

1.

5. A method for preparing a medicinal and edible composition for improving vascular dementia as described in any one of claims 1-4, characterized in that, Includes the following steps: S1: Weigh out the following ingredients by weight: steamed Polygonatum sibiricum, mulberry, wolfberry, Poria cocos, Astragalus membranaceus, donkey-hide gelatin, and Codonopsis pilosula. Add water and decoct twice. For the first decoction, add 8 to 12 times the amount of water and decoct for 0.5 to 2 hours. Filter the decoction. For the second decoction, add 6 to 10 times the amount of water and decoct for 0.5 to 2 hours. Filter the decoction and combine the filtrates. S2: Concentrate the combined filtrates into an extract, centrifuge and set aside. The concentration temperature is 60-80℃, the vacuum degree is -0.07 to -0.09MPa, and the density of the extract is 1.2-1.4g / ml. S3: Weigh the fructooligosaccharide syrup according to the weight of the extract obtained in step S2, mix the fructooligosaccharide syrup and the extract at a weight ratio of (1.5~3):1, heat, stir evenly, and cool to obtain the final product.

6. The preparation method according to claim 5, characterized in that, In step S1, add 10 times the amount of water for the first time and simmer for 1 hour; add 8 times the amount of water for the second time and simmer for 1 hour.

7. The preparation method according to claim 5, characterized in that, In step S1, the temperature for both simmerings is set at 95±5℃.

8. The preparation method according to claim 5, characterized in that, The concentration temperature in step S2 is 70°C.

9. The preparation method according to claim 5, characterized in that, In step S2, the extract is concentrated to a density of 1.3 g / ml.

10. The use of a food-derived composition for improving vascular dementia as described in any one of claims 1-4 in the preparation of a medicament for improving vascular dementia.

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