Application of water-soluble tomato concentrate in preparation of hyperviscosity intervention product

Abstract

The invention relates to a new application of a water-soluble tomato concentrate, and belongs to the technical field of medicines or dietary supplements. The water-soluble tomato concentrate disclosed by the invention has the effects of reducing low-cut whole blood viscosity, medium-cut whole blood viscosity and high-cut whole blood viscosity of a hyperviscosity rat model, the water-soluble tomato concentrate is combined with a ginkgo leaf extract and a ginseng extract for use, and all the components have a synergistic effect in the aspect of reducing the whole blood viscosity. Therefore, the water-soluble tomato concentrate and the composition thereof can be applied to medicines or dietary supplements for clinically intervening hyperviscosity, and have wide application prospects.

Description

Technical Field

[0001] This invention relates to the field of pharmaceuticals or dietary supplements, specifically to the use of water-soluble tomato concentrate in the preparation of products for the prevention, relief and / or treatment of hyperviscosity syndrome. Background Technology

[0002] Hyperviscosity syndrome is a syndrome in which blood viscosity is chronically elevated compared to normal levels due to certain factors. Blood viscosity is mainly reflected by blood viscosity index. Since blood is a non-Newtonian fluid, its viscosity is not a constant value (Rosencranz et al., 2006, Am J Clin Pathol, 125: S78-86). Blood consists of solid cellular components and liquid intercellular fluid substances, and its viscosity is determined by the characteristics of the solid and liquid phases and their relative contributions to the total blood volume (Baskurt et al., 2003, Semin Thromb Hemost, 29(5): 435-50; Elie et al., 2019, Front Physiol, 10(1329)).

[0003] Red blood cells are the most numerous formed elements in blood, and their characteristics (including hematocrit, aggregation, and deformability) are the most important factors affecting whole blood viscosity (Pop et al., 2002, Neph Heart J, 10(12): 512-516; Aimee et al., 2012, Cardiovasc Drugs Ther, 26(4): 339-48; Elie et al., 2019, Front Physiol, 10: 1329; Baskurt et al., 2024, Semin Thromb Hemost, 50(6): 902-915). Studies have shown that there is an exponential relationship between hematocrit and whole blood viscosity, that is, at higher hematocrit levels, blood viscosity becomes increasingly sensitive to changes in hematocrit (Baskurt et al., 2003, Semin Thromb Hemost, 29(5): 435-50). Studies have shown that a 1% increase in hematocrit increases blood viscosity by approximately 4% (Baskurt et al., 2003, Semin Thromb Hemost, 29(5):435-50; Michael et al., 2016, Exp Physiol, 101(2):332-42). Erythrocyte aggregation refers to the phenomenon of erythrocytes forming a three-dimensional stacked structure under low shear rates. The cellular properties of erythrocytes themselves, such as surface charge, affect erythrocyte aggregation. In addition, plasma proteins and other macromolecules also affect erythrocyte aggregation (Rampling et al., 2006, Bioheology, 41(2):91-112; Meiselman et al., 2007, Indian J Exp Biol, 45(1):9-17). Erythrocyte aggregation mainly occurs in low shear rate regions, such as veins or bifurcation points. Increased erythrocyte aggregation leads to a significant increase in blood viscosity in these areas (Baskurt et al., 2007, Hemorheology and Hemodynamics, 322-338). Therefore, at low shear rates, whole blood viscosity is mainly related to the degree of erythrocyte aggregation. Erythrocytes respond to external forces through extensive changes in their shape, and the degree of deformation under a specific force is called erythrocyte deformability (Mohandas et al., 1993, Semin Hematol, 30:171-192).Erythrocyte deformability is another important factor affecting whole blood viscosity, mainly influenced by cytoplasmic viscosity, membrane viscoelasticity, and cell sphericity (Clark et al., 1983, Blood, 61:899-910; Renoux et al., 2019, Sci Rep, 9:6771). The erythrocyte deformability index and erythrocyte rigidity index are two important indicators reflecting deformability. At low shear rates, erythrocytes with low deformability are less likely to aggregate than those with high deformability, while at high shear rates, decreased erythrocyte deformability leads to increased whole blood viscosity (Chien et al., 1970, Am J Physiol, 219:136-142). Therefore, at high shear rates, whole blood viscosity is mainly related to erythrocyte deformability.

[0004] Besides the properties of red blood cells, plasma, as the suspension medium of cellular components in the blood, also directly affects whole blood viscosity due to changes in its viscosity. Plasma is a Newtonian fluid, and its viscosity does not change with shear rate. Plasma viscosity mainly depends on the concentration of its macromolecular proteins, such as fibrinogen and immunoglobulins (Connes et al., 2008, Clin Hemorheol Microcirc, 39:179-184). Furthermore, an increase in macromolecular proteins in plasma can induce an increase in red blood cell aggregation, thereby increasing whole blood viscosity (Meiselman et al., 2007, Indian J Exp Biol, 45(1):9-17).

[0005] Other components of blood, such as white blood cells and platelets, account for less than 1% of the blood. Their number and volume concentration are relatively small compared to other cellular components in the blood, so they usually do not have a significant impact on blood viscosity (Baskurt et al., 2003, Semin Thromb Hemost, 29(5):435-50). Studies have shown that although platelets are relatively inelastic particles, they do not affect blood viscosity under normal conditions (Haszon et al., 2003, Eur J Pediatr, 162:385-390; Alarcon et al., 2005, Neonatal Hematology).

[0006] Abnormal blood viscosity is a high-risk factor for various diseases such as arteriosclerosis, hyperlipidemia, and hypertension. It is also a prominent manifestation of systemic reactions in the acute phase of cardiovascular and cerebrovascular diseases, significantly impacting their prognosis. In recent years, it has attracted widespread attention in the treatment and prevention of cardiovascular and cerebrovascular diseases. Studies show that with rapid socioeconomic development and the continuous improvement of people's living standards, hyperviscosity syndrome is not only more prevalent in the elderly but its incidence has also increased significantly across all age groups. Currently, commonly used drugs for treating hyperviscosity syndrome include low molecular weight dextran, fibrinogen-degrading agents, acetaminophen injection, and vinpocetine, among others. Their mechanisms of action differ. For example, low molecular weight dextran primarily reduces blood viscosity by increasing the negative charge on the surface of erythrocytes, thereby inhibiting their aggregation; fibrinogen-degrading agents and acetaminophen injection primarily reduce blood viscosity by promoting fibrinogen degradation; and vinpocetine primarily reduces blood viscosity by inhibiting erythrocyte aggregation and enhancing erythrocyte deformability. However, most existing drugs are injectable formulations and often have significant toxic side effects, with many contraindications, making them unsuitable for prevention or long-term use. Therefore, developing products that can effectively prevent or improve hyperviscosity syndrome is of great significance for promoting the body's health and reducing the occurrence and development of cardiovascular diseases.

[0007] Provis Natural Products Ltd. has developed a water-soluble tomato concentrate (WSTC), dubbed "natural aspirin," which has a very strong inhibitory effect on platelet aggregation and no adverse reactions such as gastrointestinal bleeding. It is expected to have a very good application prospect in the prevention and treatment of cerebral thrombosis. In 2009, Provis Natural Products Ltd. applied to EFSA (European Food Safety Authority) for a health claim that "WSTC can reduce platelet aggregation, keep blood flowing and reduce the tendency to coagulate, thereby maintaining healthy blood flow." The expert panel believed that existing studies only measured platelet aggregation indicators, so the wording "helps maintain normal platelet aggregation" was consistent with scientific evidence. However, "blood flow" depends on many other factors that have not been studied, so the wording "keeps blood flowing and reduces the tendency to coagulate, thereby maintaining healthy blood flow" does not reflect scientific evidence (The EFSA Journal (2009) 1101, 1-15). Summary of the Invention

[0008] Based on this, the present invention provides a new use of water-soluble tomato concentrate, relating to the application of water-soluble tomato concentrate in the preparation of products for the intervention of hyperviscosity syndrome.

[0009] This invention provides the use of water-soluble tomato concentrate in the preparation of products for the prevention, relief and / or treatment of hyperviscosity syndrome.

[0010] In some specific implementations, the prevention, mitigation, and / or treatment of hyperviscosity syndrome refers to reducing blood viscosity.

[0011] In some specific implementations, the prevention, mitigation, and / or treatment of hyperviscosity syndrome refers to reducing whole blood viscosity.

[0012] In some specific implementations, the prevention, mitigation, and / or treatment of hyperviscosity syndrome refers to reducing low-shear whole blood viscosity, medium-shear whole blood viscosity, and / or high-shear whole blood viscosity.

[0013] In some specific implementations, the prevention, mitigation, and / or treatment of hyperviscosity syndrome refers to reducing low-shear whole blood viscosity, medium-shear whole blood viscosity, and high-shear whole blood viscosity.

[0014] In some specific implementations, the hyperviscosity syndrome refers to hyperviscosity syndrome caused by abnormalities in plasma viscosity, hematocrit, erythrocyte aggregation, and / or erythrocyte deformability.

[0015] In some specific implementations, the hyperviscosity syndrome refers to hyperviscosity syndrome caused by increased plasma viscosity, increased hematocrit, increased erythrocyte aggregation, and / or decreased erythrocyte deformability.

[0016] In some specific implementations, the hyperviscosity syndrome refers to hyperviscosity syndrome caused by increased plasma viscosity, increased hematocrit, increased erythrocyte aggregation, and decreased erythrocyte deformability.

[0017] In some specific embodiments, the product also includes ginkgo leaf extract and / or ginseng extract.

[0018] In some specific embodiments, the product also includes ginkgo leaf extract and ginseng extract.

[0019] In some specific embodiments, the mass ratio of the water-soluble tomato concentrate, ginkgo leaf extract and ginseng extract is 1-5:1-5:1-10, preferably 2-5:2-5:2-8, and more preferably 2-5:2:2-8.

[0020] In some specific embodiments, the mass ratio of the water-soluble tomato concentrate, ginkgo leaf extract, and ginseng extract is 5:2:8.

[0021] In some specific embodiments, the mass ratio of the water-soluble tomato concentrate, ginkgo leaf extract, and ginseng extract is 1:1:4.

[0022] In some specific implementations, the product is a pharmaceutical product or a dietary supplement.

[0023] In some specific implementations, the product is in the form of tablets, capsules, or powder.

[0024] In some specific embodiments, the product is a tablet, and the product further includes excipients, which preferably include one or more of the following: microcrystalline cellulose, anhydrous lactose, croscarmellose sodium, silicon dioxide, and magnesium stearate.

[0025] Terminology Definition

[0026] In this invention, unless otherwise stated, the scientific and technical terms used herein have the meanings commonly understood by those skilled in the art. Furthermore, to better understand this invention, definitions and explanations of relevant terms are provided below.

[0027] As used in this article, the term "hyperviscosity syndrome," along with "hyperviscosity disorder," "high blood viscosity syndrome," "hyperviscosity stasis syndrome," and "blood hyperviscosity syndrome," refers to a syndrome in which blood viscosity remains elevated compared to normal levels for an extended period due to certain factors. Blood viscosity can be reflected by blood viscosity indicators.

[0028] As used herein, the term "viscosity" refers to the internal friction generated within a fluid due to intermolecular forces, and is a physical quantity that measures the viscosity of a fluid. As used herein, the term "blood viscosity" refers to the internal friction generated within blood due to intermolecular forces, reflecting the degree of viscosity of blood as it flows within blood vessels, and is represented by whole blood viscosity. As used herein, the term "whole blood viscosity" refers to the viscosity of the entire blood, including the combined effect of blood cells and plasma, and is a specific measurement indicator of blood viscosity. As used herein, the term "plasma viscosity" refers to the viscosity of plasma, which mainly depends on the concentration of plasma proteins (especially fibrinogen).

[0029] As used in this article, the term "hematocrit" refers to the ratio of the volume of red blood cells that settle and compress after a certain amount of anticoagulated whole blood has been centrifuged at a specified speed and time to the volume of whole blood, reflecting the proportion of red blood cells in the total blood volume.

[0030] As used in this article, the term "erythrocyte aggregation" refers to the ability of erythrocytes to aggregate in the blood, usually reflected by the erythrocyte aggregation index. The higher the erythrocyte aggregation index, the stronger the erythrocyte aggregation.

[0031] As used in this article, the term "erythrocyte deformability" refers to the property of erythrocytes to change shape under external force. It is usually reflected by the erythrocyte deformability index and the erythrocyte rigidity index. The higher the erythrocyte deformability index and the lower the erythrocyte rigidity index, the better the erythrocyte deformability.

[0032] As used in this article, the term "shear rate" is synonymous with "shear displacement rate" or "shear velocity," referring to the velocity gradient perpendicular to the pipe wall caused by the different velocities of different layers within the fluid as it flows in a pipe. Blood exhibits non-Newtonian fluid properties, and its viscosity varies with the shear rate. Low shear rates are typically found in microvascular regions (such as capillaries), also known as low shear rate regions; high shear rates are typically found in large vascular regions (such as the aorta), also known as high shear rate regions.

[0033] Beneficial effects of the invention

[0034] This invention unexpectedly discovers a novel use for water-soluble tomato concentrate in the prevention, relief, and / or treatment of hyperviscosity syndrome, specifically in the preparation of pharmaceuticals or dietary supplements for treating hyperviscosity syndrome. Animal studies have shown that water-soluble tomato concentrate reduces low-shear, medium-shear, and high-shear whole blood viscosity in a rat model of hyperviscosity syndrome. Furthermore, this invention reveals a synergistic effect in reducing whole blood viscosity when water-soluble tomato concentrate is combined with ginkgo biloba extract and ginseng extract. Therefore, it is expected that water-soluble tomato concentrate and its compositions can be applied in pharmaceuticals or dietary supplements for clinical intervention in hyperviscosity syndrome. This offers high activity, significantly reducing clinical dosage and alleviating the burden of medication for patients. Moreover, it is extracted from tomatoes using physical methods, making it widely available, with minimal toxicity and high safety, and possesses broad application prospects. Detailed Implementation

[0035] To further illustrate the technical means and effects of the present invention, the following describes the technical solution of the present invention in conjunction with preferred embodiments of the present invention. However, the present invention is not limited to the scope of the embodiments.

[0036] Furthermore, unless specific conditions are specified in the examples, conventional conditions or conditions recommended by the manufacturer should be followed. Reagents or instruments whose manufacturers are not specified are all commercially available conventional products. Those skilled in the art will understand that the examples are described by way of illustration and are not intended to limit the scope of protection claimed by the invention. All disclosures and other references mentioned herein are incorporated herein by reference in their entirety.

[0037] The optional range of the term "and / or" as used herein includes any one of two or more of the related listed items, as well as any and all combinations of the related listed items, including any two related listed items, any more related listed items, or a combination of all the related listed items.

[0038] In this article, "one or more" refers to any one, two or more of the listed items.

[0039] Water-soluble tomato concentrate is an extract derived from tomatoes. It is primarily obtained by separating water-soluble components from tomatoes using physical methods (centrifugation, filtration, etc.), followed by concentration and desaccharification. Its main characteristic components are nucleoside compounds, flavonoids, and phenolic acids. Currently, water-soluble tomato concentrate is regulated as a general food product in Europe, the United States, and my country.

[0040] Water-soluble tomato concentrate (WSTC) is mainly composed of heat-stable water-soluble compounds derived from tomatoes, which are its main bioactive components. The main bioactive components in WSTC may originate from the pulp of tomato fruit and / or the juice surrounding the seeds. After further removal of insoluble solids, fat-soluble components, and water-soluble sugars from these sources, followed by concentration and drying, WSTC is obtained. The water-soluble compounds in WSTC include nucleoside compounds, flavonoids, and phenolic acids. Nucleoside compounds can be the nucleoside compound itself or its phosphorylated nucleotides. Nucleoside compounds may be selected from at least one of uridine, cytidine, adenosine, and guanosine; more preferably, they are at least one of adenosine, adenosine-3'-monophosphate, and adenosine-5'-monophosphate. Flavonoids can be flavonoids themselves or their glycosylated products. Flavonoids may be selected from at least one of myricetin, luteolin, kaempferol, and naringenin; more preferably, quercetin-3-O-glucoside, naringin, and rutin. Phenolic acids can be phenolic acids themselves or their glycosylated products. Phenolic acids may be cinnamic acid or its derivatives, such as p-coumaric acid, caffeic acid, coumaric acid, ferulic acid, and sinapic acid; phenolic acids may be benzoic acid or its derivatives, such as at least one of p-hydroxybenzoic acid, chlorogenic acid, gallic acid, vanillic acid, and syringic acid. It is understood that the bioactive components in WSTC are not limited to one or more of the substances listed above, and may also contain other substances.

[0041] Furthermore, the water-soluble tomato concentrate of this invention is lycopene-free or substantially lycopene-free. The water-soluble tomato concentrate is substantially free of water-insoluble particulate matter.

[0042] In addition, water-soluble tomato concentrate can be formulated with food- or pharmaceutically acceptable excipients to improve its commercial properties, including delivery, shelf life, and taste.

[0043] The water-soluble tomato concentrate described in this invention can be purchased from Provis Natural Products Ltd. or its authorized sales agents. WO 99 / 55350, WO 2010 / 049707, and CN102271697 also disclose methods for manufacturing the water-soluble tomato concentrate used in this invention. Therefore, the water-soluble tomato concentrate used in this invention can also be prepared in-house according to WO 99 / 55350, WO 2010 / 049707, or CN102271697. If prepared in-house according to the methods described in WO 99 / 55350, WO 2010 / 049707, or CN102271697, the composition of the resulting water-soluble tomato concentrate should meet the above requirements. For example, the process method described in CN102271697 can be considered a preferred method for manufacturing the water-soluble tomato concentrate.

[0044] Without limitation, the water-soluble tomato concentrate of the present invention can be prepared by the following method, and the effect of the present invention in intervening in hyperviscosity syndrome can be achieved. The method for preparing the water-soluble tomato concentrate includes the following steps:

[0045] (a) The initial mixture for preparing tomato homogenate;

[0046] (b) Separate the water-soluble components from the initial mixture at a temperature not exceeding 60°C;

[0047] (c) Filter and concentrate the water-soluble components at a temperature not exceeding 60°C.

[0048] In some embodiments, the temperature of the initial mixture in step (a) is not higher than 35°C.

[0049] In some embodiments, the pH of the initial mixture in step (a) does not exceed 5.5.

[0050] In some embodiments, the browning index of the initial mixture does not exceed 0.4 AU at 4% solids, wherein the browning index is defined as the absorbance of the soluble portion at 420 nm.

[0051] In some embodiments, step (b) involves separating and removing water-insoluble solids with a particle size greater than 500 μm from mixture A to obtain a water-soluble component.

[0052] In some embodiments, the separation in step (b) includes at least one of centrifugal separation and natural sedimentation separation, and the water-soluble component is the supernatant obtained after separation.

[0053] In some embodiments, filtration in step (c) is performed using a filter membrane. Without limitation, the pore size of the filter membrane used for filtration is no greater than 1 μm, specifically 0.2 μm.

[0054] In some implementations, the concentration in step (c) may be achieved by membrane filtration concentration, low-temperature evaporation concentration, freeze-drying concentration, or spray drying concentration.

[0055] In some embodiments, step (c) further includes a step of removing free sugars from the water-soluble component before filtration.

[0056] In some implementations, the intervention for hyperviscosity syndrome refers to the prevention, relief, and / or treatment of hyperviscosity syndrome.

[0057] In some implementations, the prevention, mitigation, and / or treatment of hyperviscosity syndrome refers to reducing blood viscosity.

[0058] In some implementations, the prevention, mitigation, and / or treatment of hyperviscosity syndrome refers to reducing whole blood viscosity.

[0059] In some implementations, the prevention, mitigation, and / or treatment of hyperviscosity syndrome refers to reducing low-shear whole blood viscosity, medium-shear whole blood viscosity, and / or high-shear whole blood viscosity.

[0060] In some implementations, the prevention, mitigation, and / or treatment of hyperviscosity syndrome refers to reducing low-shear whole blood viscosity, medium-shear whole blood viscosity, and high-shear whole blood viscosity.

[0061] In some implementations, the hyperviscosity syndrome refers to hyperviscosity syndrome caused by abnormalities in plasma viscosity, hematocrit, erythrocyte aggregation, and / or erythrocyte deformability.

[0062] In some implementations, the hyperviscosity syndrome refers to hyperviscosity syndrome caused by increased plasma viscosity, increased hematocrit, increased erythrocyte aggregation, and / or decreased erythrocyte deformability.

[0063] In some implementations, the hyperviscosity syndrome refers to hyperviscosity syndrome caused by increased plasma viscosity, increased hematocrit, increased erythrocyte aggregation, and decreased erythrocyte deformability.

[0064] In some embodiments, the product further includes ginkgo leaf extract and / or ginseng extract.

[0065] In some embodiments, the product also includes ginkgo leaf extract and ginseng extract.

[0066] In some embodiments, the mass ratio of the water-soluble tomato concentrate, ginkgo leaf extract and ginseng extract is 1-5:1-5:1-10, preferably 2-5:2-5:2-8, and more preferably 2-5:2:2-8.

[0067] In some embodiments, the mass ratio of the water-soluble tomato concentrate, ginkgo leaf extract, and ginseng extract is 5:2:8.

[0068] In some embodiments, the mass ratio of the water-soluble tomato concentrate, ginkgo leaf extract, and ginseng extract is 1:1:4.

[0069] In some implementations, the product is a pharmaceutical product or a dietary supplement.

[0070] In some embodiments, the product is in the form of tablets, capsules, or powder.

[0071] In some embodiments, the product is a tablet, and the product further includes excipients, which preferably include one or more of the following: microcrystalline cellulose, anhydrous lactose, croscarmellose sodium, silica, and magnesium stearate.

[0072] For experimental parameters not specified in the following specific embodiments, please refer to the guidelines given in this invention document first, or refer to experimental manuals or other experimental methods known in the art, or refer to the experimental conditions recommended by the manufacturer.

[0073] The raw materials and reagents involved in the following specific embodiments can be obtained commercially or prepared by those skilled in the art using known methods.

[0074] The water-soluble tomato concentrate used in this embodiment of the invention was purchased from Provis Natural Products Ltd., which is marketed in Europe as [product name missing]. It is sold in mainland China. To conduct sales.

[0075] The main active ingredients of ginkgo leaf extract are flavonol glycosides and terpene lactones, while the main active ingredient of ginseng extract is ginsenosides. Numerous basic and clinical studies have shown that both have broad therapeutic effects on cardiovascular and cerebrovascular diseases.

[0076] The Ginkgo biloba extract used in this embodiment of the invention was purchased from Ningbo Green Health Pharmaceutical Co., Ltd. The raw materials meet the requirements of the pharmacopoeia, wherein the total content of flavonol glycosides in the Ginkgo biloba extract is ≥24.0% by mass, and the content of terpene lactones in the Ginkgo biloba extract is ≥6.0% by mass.

[0077] The ginseng extract used in this embodiment of the invention was purchased from Guangdong Qingyunshan Pharmaceutical Co., Ltd., wherein the total ginsenosides (calculated as ginsenoside Re) content in the ginseng extract accounted for ≥10% by mass.

[0078] Example 1: Preparation of tablets from the composition

[0079] The specific preparation process of the composition tablets is as follows:

[0080] (1) Weighing and preparing materials: Weigh the raw materials water-soluble tomato concentrate, ginkgo leaf extract and ginseng extract in a mass ratio of 1:1:4; Weigh the excipients microcrystalline cellulose, lactose, sodium carboxymethyl starch, magnesium stearate and silicon dioxide in a mass ratio of 3.8:3.5:1:0.1:0.1 with the mass ratio of water-soluble tomato concentrate as 1.

[0081] (2) Granulation and mixing: Granulate some of the raw materials and auxiliary materials, and then add them to the mixer along with other raw materials and auxiliary materials to mix evenly.

[0082] (3) Tableting and coating: Add the evenly mixed materials into the tableting machine for tableting, and use coating powder to coat the tablets.

[0083] Example 2: Effect Test of Intervention on Hyperviscosity Syndrome

[0084] (1) Instruments and reagents

[0085] Dissection instruments, fully automated blood rheometer.

[0086] (2) Animal selection and feed

[0087] Healthy adult SD rats, weighing 400–450g, were selected, with 10 rats in each group.

[0088] (3) Experimental grouping and drug administration

[0089] The experiment included a combination group (a group of hydroxychloroquine ginkgo biloba and ginseng tablets), a water-soluble tomato concentrate group (a group of hydroxychloroquine ginkgo biloba and ginseng), a blank control group (a blank control group), and a model control group (a model control group).

[0090] (4) Test Procedure

[0091] Adaptation period: Rats in each group were fed a maintenance diet under the barrier system and observed for 5-7 days.

[0092] Modeling period: Animals in each group were given the corresponding sample by gavage once a day for 14 consecutive days. The blank control group (blank group) and the model control group (model group) were given the same volume of solvent by gavage.

[0093] The dosage of the combination group (Qingluosu Ginkgo Biloba Ginseng Tablets Group) was 187.5 mg / kg.

[0094] The dosage of the water-soluble tomato concentrate group (hydroxytocopherol group) was 12.5 mg / kg.

[0095] The dosage for the Ginkgo biloba and ginseng group was 62.5 mg / kg.

[0096] On day 8 after drug administration, except for the control group, rats in other groups were placed in an ice-water bath (temperature 0-4℃) daily until they became rigid, and then removed. This ice-water modeling was continued for one week. The day after the last ice-water modeling, except for the control group, rats in other groups received a first subcutaneous injection of epinephrine hydrochloride 2 hours after the last drug administration, followed by a second subcutaneous injection of epinephrine hydrochloride 4 hours later. Each injection was 1 mg / mL epinephrine hydrochloride injection (0.8 mL / kg). At approximately 9:00 AM the day after injection, the rats' vital signs were observed, and blood samples were collected for laboratory testing.

[0097] (5) Detection indicators

[0098] Low-shear whole blood viscosity, medium-shear whole blood viscosity, high-shear whole blood viscosity, plasma viscosity, hematocrit, erythrocyte aggregation index, erythrocyte deformability index, and erythrocyte rigidity index.

[0099] (6) Data Statistical Methods

[0100] Data are expressed as (X±SD), and statistical analysis was performed using Graphpad Prism 10 software. For quantitative data, if the variances are homogeneous or homogeneous after transformation, the Tukey test in one-way ANOVA was used. If the variances are unequal, and remain unequal after transformation, the rank-sum test was used for statistical analysis.

[0101] Table 1 Whole blood viscosity and plasma viscosity

[0102]

[0103] Note: Compared with the blank group, * P<0.05, ** P<0.01, *** P < 0.001; compared with the model group, # P<0.05, ## P<0.01, ### P<0.001; compared with the group containing chlorogenic acid, ginkgo biloba and ginseng tablets, ▲ P<0.05, ▲▲ P<0.01, ▲▲▲ P<0.001.

[0104] Table 2 Erythrocyte Indicators

[0105]

[0106] Note: Compared with the blank group, * P<0.05, ** P<0.01, *** P < 0.001; compared with the model group, # P<0.05, ##P<0.01, ### P<0.001; compared with the group containing chlorogenic acid, ginkgo biloba and ginseng tablets, ▲ P<0.05, ▲▲ P<0.01, ▲▲▲ P<0.001.

[0107] The experimental results showed that, under the experimental conditions, compared with the control group, the model group exhibited significantly increased low-shear whole blood viscosity, medium-shear whole blood viscosity, high-shear whole blood viscosity, plasma viscosity, hematocrit, erythrocyte aggregation index, and erythrocyte rigidity index (P<0.001), and significantly decreased erythrocyte deformability index (P<0.001), indicating successful model establishment. Compared with the model group, the erythrocyte erythrocyte erythrocyte erythrocyte erythrocyte erythrocyte erythrocyte aggregation index and erythrocyte rigidity index (P<0.05, P<0.01, or P<0.001), and significantly increased erythrocyte deformability index (P<0.001). Compared with the model group, the Ginkgo biloba leaf and ginseng group showed significantly decreased low-shear whole blood viscosity, medium-shear whole blood viscosity, high-shear whole blood viscosity, plasma viscosity, hematocrit, erythrocyte aggregation index, and erythrocyte rigidity index (P<0.05, P<0.01, or P<0.001), and significantly increased erythrocyte deformability index (P<0.001). Compared with the model group, the Qingluosu Ginkgo biloba leaf and ginseng tablet group showed significantly decreased low-shear whole blood viscosity, medium-shear whole blood viscosity, high-shear whole blood viscosity, plasma viscosity, hematocrit, erythrocyte aggregation index, and erythrocyte rigidity index (P<0.001), and significantly increased erythrocyte deformability index (P<0.001). Compared with the Qingluosu group and the Ginkgo biloba and ginseng group, the Qingluosu Ginkgo biloba and ginseng tablet group showed significant differences in the improvement of low-shear whole blood viscosity, medium-shear whole blood viscosity, high-shear whole blood viscosity, plasma viscosity, hematocrit, erythrocyte aggregation index, erythrocyte deformability index and erythrocyte rigidity index (P<0.05, P<0.01 or P<0.001).

[0108] The synergistic effect of the composition was evaluated using the Jin Zhengjun Q-value method. A Q value between 0.85 and 1.15 was considered a simple additive effect, between 1.15 and 20 was considered an enhanced effect, and >20 was considered a significant enhanced effect. The calculation formula is as follows:

[0109] Q = E obs(实测效应) / (E A +E B -E A ×E B ) (预期相加效应)

[0110] Calculations showed that the Q values ​​of hydroxychloroquine combined with ginkgo biloba and ginseng in improving low-shear whole blood viscosity, medium-shear whole blood viscosity, high-shear whole blood viscosity, and plasma viscosity were 1.27, 1.09, 1.19, and 1.86, respectively, indicating that the composition had a synergistic effect in improving low-shear whole blood viscosity, high-shear whole blood viscosity, and plasma viscosity. Similarly, the Q values ​​of hydroxychloroquine combined with ginkgo biloba and ginseng in regulating hematocrit, erythrocyte aggregation index, and erythrocyte rigidity index were 1.26, 1.16, and 1.18, respectively, indicating that the composition had a synergistic effect in improving hematocrit, erythrocyte aggregation index, and erythrocyte rigidity index.

[0111] The above experimental results demonstrate that the water-soluble tomato concentrate of the present invention has the effect of reducing low-shear, medium-shear, and high-shear whole blood viscosity in a rat model of hyperviscosity syndrome. It can reduce whole blood viscosity and improve hyperviscosity syndrome by reducing hematocrit, reducing erythrocyte aggregation, increasing erythrocyte deformability, and reducing plasma viscosity. In addition, the composition has an unexpected synergistic effect compared with the single component.

Claims

1. Application of water-soluble tomato concentrate in the preparation of products for the prevention, relief and / or treatment of hyperviscosity syndrome.

2. The application according to claim 1, characterized in that, The prevention, relief, and / or treatment of hyperviscosity syndrome refers to reducing whole blood viscosity.

3. The application according to claim 1, characterized in that, The prevention, relief and / or treatment of hyperviscosity syndrome refers to reducing low-shear whole blood viscosity, medium-shear whole blood viscosity and / or high-shear whole blood viscosity.

4. The application according to claim 1, characterized in that, The hyperviscosity syndrome refers to hyperviscosity syndrome caused by increased plasma viscosity, increased hematocrit, increased erythrocyte aggregation, and / or decreased erythrocyte deformability.

5. The application according to claim 1, characterized in that, The product also includes ginkgo leaf extract and / or ginseng extract.

6. The application according to claim 5, characterized in that, The mass ratio of the water-soluble tomato concentrate, ginkgo leaf extract, and ginseng extract is 1-5:1-5:1-10; preferably 2-5:2:

8.

7. The application according to claim 5, characterized in that, The mass ratio of the water-soluble tomato concentrate, ginkgo leaf extract, and ginseng extract is 1:1:

4.

8. The application according to claim 1, characterized in that, The product is a medicine or dietary supplement.

9. The application according to claim 1, characterized in that, The product is available in tablet, capsule, or powder form.

10. The application according to claim 9, characterized in that, The product is in tablet form and also includes excipients, which preferably include one or more of the following: microcrystalline cellulose, anhydrous lactose, croscarmellose sodium, silicon dioxide, and magnesium stearate.

Images