New application of edible rubber seed oil in treatment of hemorrhagic diseases

Abstract

The invention provides an application of edible rubber seed oil in preparation of a medicine or nutritious food for preventing and / or treating hemorrhagic diseases. The edible rubber seed oil can be used for preventing and / or treating liver hemorrhage, cardiac hemorrhage and cerebral hemorrhage. The invention can provide a new safer nutritional food choice for bleeding of different organs such as liver, heart, brain and the like.

Description

Technical Field

[0001] This invention relates to the fields of biomedicine and nutritional food technology, specifically to the novel use of edible rubber seed oil in the preparation of medicines or nutritional foods for the treatment and / or prevention of hemorrhagic diseases. Background Technology

[0002] Clinical observations have revealed that many hematological diseases can cause bleeding, such as immune thrombocytopenic purpura (ITP), chronic aplastic anemia (AA), acute leukemia (AL), and myelodysplastic syndromes (MDS). The bleeding mechanism in these diseases is primarily related to decreased peripheral blood platelet counts and abnormal coagulation function. Currently, in addition to treating the underlying disease, platelet transfusions, hemostatic drugs, and corticosteroids remain effective hemostatic measures for bleeding caused by hematological diseases. However, repeated clinical use can lead to decreased treatment efficacy because platelet transfusion antibodies can cause treatment ineffectiveness or dependence.

[0003] In the 1970s, Chinese researchers studied rubber tree seed oil. Animal experiments showed that it did not affect animal growth, reproduction, or health, nor did it exhibit teratogenic, mutagenic, or carcinogenic effects. Refined edible rubber seed oil was then classified as an edible oil. Pharmacologically, animal experiments confirmed that it can prevent atherosclerosis in rabbits, reduce atherosclerosis in macaques, and lower experimentally induced hyperlipidemia in rats. Clinical trials have shown that it can lower triglycerides and cholesterol in patients with hyperlipidemia.

[0004] This invention relates to edible rubber seed oil, extracted from the crude oil of rubber tree seeds. It is not only high in unsaturated fatty acids but also rich in active ingredients such as polyphenols, triterpenes, flavonoids, and small-molecule active peptides. Currently, most research is based on rubber tree seed oil, and studies on the optimal dosage and safety of edible rubber seed oil are not yet in-depth or systematic, indicating significant research potential and exploratory value. Chinese patent application CN 120114504 A discloses the anti-fatigue use of rubber tree seed oil. Chinese patent application CN 120114503 A discloses the anti-hypoxia use of rubber tree seed oil.

[0005] With the arrival of an aging society and changes in people's dietary and lifestyle habits, the incidence of hemorrhagic diseases is increasing rapidly every year. The high rates of disability and mortality have led to widespread poverty among families, posing a serious social problem. At the same time, the exorbitant medical costs have placed a heavy burden on the national medical insurance system. Existing treatment methods have certain limitations. Edible rubber seed oil, as a natural active ingredient, has advantages such as wide availability and relatively high safety. Further research into its role in improving hemorrhagic diseases holds promise for the development of novel drugs or functional nutritional foods, showing broad application prospects. Summary of the Invention

[0006] The purpose of this invention is to provide a new use for edible rubber seed oil, specifically, the use of edible rubber seed oil in the preparation of medicines or nutritional foods for the prevention and / or treatment of hemorrhagic diseases.

[0007] This invention is achieved through the following technical solution: As one aspect of the present invention, the present invention provides the use of edible rubber seed oil in the preparation of medicines or nutritional foods for the prevention and / or treatment of hemorrhagic diseases.

[0008] Preferably, the hemorrhagic disease is a disease caused by statins.

[0009] More preferably, the hemorrhagic disease includes liver hemorrhage, heart hemorrhage, or brain hemorrhage.

[0010] Preferably, the drug or nutritional food uses edible rubber seed oil as the sole active ingredient.

[0011] Preferably, the medicine or nutritional food is a compound of two or more food ingredients, at least one of which is edible rubber seed oil; other ingredients include bamboo leaf flavonoids, earthworm protein, phytosterols, etc.

[0012] Further preferably, the drug or nutritional food also contains pharmaceutically acceptable excipients. These pharmaceutically acceptable excipients include fillers, emulsifiers, and suspending agents. Fillers include perilla seed oil, flaxseed oil, gardenia oil, sacha inchi oil, flaxseed oil, tomato seed oil, and krill oil; emulsifiers include phospholipids; and suspending agents include beeswax and silica.

[0013] Preferably, the edible rubber seed oil contains 34%~42% linoleic acid, 15%~25% linolenic acid, and a total flavonoid content >11mg / g.

[0014] The beneficial effects of this invention are: This invention proposes a new use for edible rubber seed oil in the preparation of products that improve bleeding.

[0015] 1. A zebrafish liver hemorrhage model was established by administering simvastatin. Consuming rubber seed oil has the effect of improving liver hemorrhage, specifically by reducing the rate of liver hemorrhage.

[0016] 2. A zebrafish cardiac hemorrhage model was established by administering simvastatin. Consuming rubber seed oil has the effect of improving cardiac hemorrhage, specifically by reducing the cardiac hemorrhage rate.

[0017] 3. A zebrafish cerebral hemorrhage model was established by administering simvastatin. Rubber seed oil showed efficacy in improving cerebral hemorrhage, specifically by reducing the rate of cerebral hemorrhage.

[0018] In summary, edible rubber seed oil can be used to prevent and / or treat liver hemorrhage, cardiac hemorrhage, and cerebral hemorrhage. This invention provides a new and safer nutritional food option for hemorrhage in different organs such as the liver, heart, and brain. Attached Figure Description

[0019] Figure 1 This is a typical graph showing the incidence of liver hemorrhage in zebrafish after four different treatments in Example 1. The dashed area represents the zebrafish liver.

[0020] Figure 2 The incidence of liver hemorrhage in zebrafish after four different treatments in Example 1.

[0021] Figure 3 This is a typical graph showing the incidence of cardiac hemorrhage in zebrafish after four different treatments in Example 2. The dashed area represents the zebrafish heart.

[0022] Figure 4 The incidence of cardiac hemorrhage in zebrafish after four different treatments in Example 2.

[0023] Figure 5 This is a typical graph showing the incidence of cerebral hemorrhage in zebrafish after four different treatments in Example 3. The dotted line area represents the zebrafish brain.

[0024] Figure 6 The brain hemorrhage rate of zebrafish after four different treatments in Example 3. Detailed Implementation

[0025] This invention provides the application of edible rubber seed oil in the preparation of medicines or nutritional foods for the prevention and / or treatment of hemorrhagic diseases.

[0026] Preferably, the hemorrhagic disease includes liver hemorrhage, heart hemorrhage, or brain hemorrhage.

[0027] More preferably, the hemorrhagic disease is a disease caused by statins.

[0028] Preferably, the drug or nutritional food uses edible rubber seed oil as the sole active ingredient.

[0029] Preferably, the medicine or nutritional food is a compound of two or more food ingredients, wherein at least one ingredient is edible rubber seed oil; other ingredients include bamboo leaf flavonoids.

[0030] The following examples illustrate the evaluation of the efficacy of edible rubber seed oil in improving hemorrhage using a zebrafish model. Zebrafish share an 87% genome similarity with humans, and their cardiovascular, nervous, and metabolic systems exhibit high similarity in anatomical structure, physiological characteristics, and molecular physiology with mammals. Furthermore, their embryos and juveniles are transparent, facilitating direct observation of organs, making them an ideal model for efficacy studies. By inducing hemorrhage-like lesions in the liver, heart, and brain using specific methods, the effects of drugs on hemorrhage formation were observed, and potential interventions or treatment strategies were explored. This is the first time the zebrafish model has been used to evaluate the efficacy of rubber seed oil in improving hemorrhage.

[0031] Example 1 This embodiment uses zebrafish experiments to confirm the efficacy of edible rubber seed oil in improving liver bleeding.

[0032] Experimental animals: Zebrafish were raised in aquarium water at 28℃ (water quality: 200mg of instant sea salt added per 1L of reverse osmosis water, conductivity 450~550 μS / cm; pH 6.5~8.5; hardness 50~100 mg / L CaCO3), provided by Huante Biotechnology Co., Ltd. The experimental animal use license number is: SYXK (Zhejiang) 2022-0004, and the husbandry and management meet the requirements of international AAALAC certification (certification number: 001458), and the IACUC ethics review number is: IACUC-2025-202508250019-01.

[0033] Sample source: Edible rubber seed oil, provided by Zhiqi Health Industry (Shandong) Group Co., Ltd., batch number: 20250801; quality report shows: linoleic acid content wt 34.0~42.0%, linolenic acid content wt 15~25.0%, total flavonoid content >11mg / g; icariin, batch number K1624039, light yellow powder, Shanghai Aladdin Biochemical Technology Co., Ltd., solvent is DMSO.

[0034] Experimental Groups: The samples were divided into an edible rubber seed oil sample group, a positive control icariin group, and a normal control group and a model control group.

[0035] Edible rubber seed oil sample group: 1000.0 μg / mL concentration; Icariin group: 50.0 μg / mL concentration; Experimental Methods: Wild-type AB strain zebrafish, 4 days post-fertilization (4 dpf), were randomly selected and placed in 6-well plates, with 30 zebrafish treated in each well (experimental group). Edible rubber seed oil, 50.0 μM icariin (positive control), normal control, and model control were administered in water, with a volume of 3 mL per well. Except for the normal control group, the other experimental groups were treated with 3.00 μM simvastatin in water to establish a zebrafish liver hemorrhage model. After treatment at 28℃ for 1 day, each experimental group was observed under a dissecting microscope. Figure 1 As shown.

[0036] The number of zebrafish with hepatic hemorrhage was counted, and the incidence of hemorrhage was calculated. Statistical analysis of this index was used to evaluate the efficacy of the samples in improving hepatic hemorrhage. The results are shown in Table 1 and [Table data missing]. Figure 2 Statistical analysis using SPSS software showed that p < 0.001 was statistically significant.

[0037] Table 1. Experimental results evaluating the efficacy of the samples in improving liver bleeding (n = 30)

[0038] Compared with the model control group, p<0.001 The results showed that consuming rubber seed oil could reduce the rate of liver bleeding, with a significant difference compared to the model control group, indicating that consuming rubber seed oil has a good effect on improving liver bleeding.

[0039] Example 2 This embodiment uses zebrafish experiments to confirm the efficacy of edible rubber seed oil in improving myocardial bleeding.

[0040] Experimental animals: Zebrafish were raised in aquarium water at 28℃ (water quality: 200mg of instant sea salt added per 1L of reverse osmosis water, conductivity 450~550 μS / cm; pH 6.5~8.5; hardness 50~100 mg / L CaCO3), provided by Huante Biotechnology Co., Ltd. The experimental animal use license number is: SYXK (Zhejiang) 2022-0004, and the husbandry and management meet the requirements of international AAALAC certification (certification number: 001458), and the IACUC ethics review number is: IACUC-2025-202508250019-01.

[0041] Sample source: Edible rubber seed oil, provided by Zhiqi Health Industry (Shandong) Group Co., Ltd., batch number: 20250801; the quality report shows that the linoleic acid content is 34.0-42.0% wt, the linolenic acid content is 15-25.0% wt, and the total flavonoid content is >11mg / g; Icariin, batch number K1624039, light yellow powder, Shanghai Aladdin Biochemical Technology Co., Ltd., solvent is DMSO.

[0042] Experimental Groups: The samples were divided into an edible rubber seed oil sample group, a positive control group consisting of icariin, and a normal control group and a model control group.

[0043] Edible rubber seed oil sample group: 2000 μg / mL concentration; Icariin group: 50 μg / mL concentration; Experimental Methods: Zebrafish with melanin allele mutations 3 days post-fertilization (3 dpf) were randomly selected and placed in 6-well plates, with 30 zebrafish treated in each well (experimental group). Edible rubber seed oil was administered in water, along with a positive control of icariin at a concentration of 50.0 μM, a normal control group, and a model control group. Each well contained 3 mL of the solution. After treatment at 28℃ for 4 h, except for the normal control group, the remaining experimental groups were administered simvastatin in water to establish a zebrafish cardiac hemorrhage model. After further treatment at 28℃ for 0.5 h, each experimental group was observed under a dissecting microscope. Figure 3 As shown.

[0044] The number of zebrafish with myocardial hemorrhage was counted, and the incidence of hemorrhage was calculated. Statistical analysis of this index was used to evaluate the efficacy of the sample in improving myocardial hemorrhage. The results are shown in Table 2 and [Table data missing]. Figure 4 Statistical analysis using SPSS software showed that p < 0.001 was statistically significant.

[0045] Table 2. Experimental results evaluating the efficacy of the samples in improving myocardial hemorrhage (n = 30)

[0046] Compared with the model control group, p<0.001 The results showed that consuming rubber seed oil could reduce the incidence of myocardial hemorrhage, and the difference was statistically significant compared with the model control group, indicating that consuming rubber seed oil has a good effect on improving myocardial hemorrhage.

[0047] Example 3 This embodiment uses zebrafish experiments to confirm the efficacy of edible rubber seed oil in improving cerebral hemorrhage.

[0048] Experimental animals: Zebrafish were raised in aquarium water at 28℃ (water quality: 200mg of instant sea salt added per 1L of reverse osmosis water, conductivity 450~550 μS / cm; pH 6.5~8.5; hardness 50~100 mg / L CaCO3), provided by Huante Biotechnology Co., Ltd. The experimental animal use license number is: SYXK (Zhejiang) 2022-0004, and the husbandry and management meet the requirements of international AAALAC certification (certification number: 001458), and the IACUC ethics review number is: IACUC-2025-202508250019-01.

[0049] Sample source: Edible rubber seed oil, provided by Zhiqi Health Industry (Shandong) Group Co., Ltd., batch number: 20250801; the quality report shows that the linoleic acid content is 34.0-42.0% wt, the linolenic acid content is 15-25.0% wt, and the total flavonoid content is >11mg / g; Icariin, batch number K1624039, light yellow powder, Shanghai Aladdin Biochemical Technology Co., Ltd., solvent is DMSO.

[0050] Experimental Groups: The samples were divided into an edible rubber seed oil sample group, a positive control icariin group, and a normal control group and a model control group.

[0051] Edible rubber seed oil sample group: 1000 μg / mL concentration; Icariin group: 50 μg / mL concentration; Experimental Methods: Zebrafish with melanin allele mutations 1 day after fertilization (1 dpf) were randomly selected and placed in 6-well plates, with 30 zebrafish treated in each well (experimental group). Edible rubber seed oil, icariin (50.0 μM) as a positive control, and icariin as a model control were administered in water, with a volume of 3 mL per well. Except for the normal control group, the other experimental groups were treated with simvastatin in water to establish a zebrafish cerebral hemorrhage model. After treatment at 28℃ for 1 day, each experimental group was observed under a dissecting microscope. Figure 5 As shown.

[0052] The number of zebrafish with cerebral hemorrhage was counted, and the incidence of cerebral hemorrhage was calculated. The statistical analysis results of this index were used to evaluate the efficacy of the sample in improving cerebral hemorrhage. The results are shown in Table 3 and 4. Figure 6 Statistical analysis using SPSS software showed that p < 0.05 was statistically significant.

[0053] Table 3. Experimental results evaluating the efficacy of the samples in improving cerebral hemorrhage (n = 30)

[0054] Compared with the model control group, p<0.05, p<0.001 The results showed that consuming rubber seed oil could reduce the incidence of cerebral hemorrhage, and the difference was statistically significant compared with the model control group, indicating that consuming rubber seed oil has a good effect on improving cerebral hemorrhage.

[0055] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features. These modifications or substitutions, or combinations of technical features in the above embodiments that do not conflict with each other, can be made in accordance with the manner described in the embodiments. These modifications, substitutions or combinations do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. Application of edible rubber seed oil in the preparation of medicines or nutritional foods for the prevention and / or treatment of hemorrhagic diseases.

2. The application as described in claim 1, characterized in that, The hemorrhagic disease mentioned is a disease caused by statin drugs.

3. The application as described in claim 1, characterized in that, The hemorrhagic diseases mentioned include liver hemorrhage, heart hemorrhage, or brain hemorrhage.

4. The application as described in any one of claims 1-3, characterized in that, The drug or nutritional food uses edible rubber seed oil as its sole active ingredient.

5. The application as described in any one of claims 1-3, characterized in that, The medicine or nutritional food is a compound of two or more food ingredients, at least one of which is edible rubber seed oil.

6. The application as described in any one of claims 1-3, characterized in that, The edible rubber seed oil contains 34%~42% linoleic acid, 15%~25% linolenic acid, and a total flavonoid content of >11mg / g.

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