Xanthoceras sorbifolia oil DHA composition and use thereof in improving memory and ameliorating tic disorder

Abstract

A composition of Xanthoceras sorbifolia oil and DHA and use thereof in preparing a drug or a health care product for improving memory and ameliorating tic disorder. The composition comprises 10-90 parts by weight of Xanthoceras sorbifolia oil and 10-90 parts by weight of DHA. Xanthoceras sorbifolia oil and DHA are compounded and have a synergistic effect, thereby significantly improving the effects of Xanthoceras sorbifolia oil and DHA on improving memory and ameliorating tic disorder. The formula is concise, and the composition can effectively improve memory and ameliorate tic disorder.

Description

Xanthoceras sorbifolia oil DHA composition and its application in improving memory and tic disorders Technical Field

[0001] The invention belongs to the field of medicine and health care products, and relates to a Xanthoceras sorbifolia oil DHA composition and application thereof in improving memory and tic disorders. Background Art

[0002] Xanthoceras sorbifolia has anti-inflammatory, memory-improving, cardiovascular-improving, antiviral, anti-cancer, and anti-HIV activities; it has certain therapeutic effects on rheumatoid arthritis, swelling and pain relief, skin wind-heat syndrome, enuresis, Alzheimer's disease, hepatitis, and toxic liver damage; it can lower cholesterol and blood lipids; and it has high inhibitory activity on 6 types of cancer cells.

[0003] Xanthoceras sorbifolia seeds contain approximately 35% oil, while the kernels contain over 60%. Nutritionally, Xanthoceras sorbifolia oil is an edible vegetable oil rich in unsaturated fatty acids. In addition to oleic and linoleic acids, it also contains a rare functional ingredient, nervonic acid, at a concentration of approximately 3%. However, Xanthoceras sorbifolia cultivation has a relatively short history, and historical records of its use among the general public are sporadic and incomplete. Furthermore, due to the lack of large-scale cultivation, Xanthoceras sorbifolia oil is scarce, making it expensive and difficult to widely use.

[0004] CN1972702B discloses the composition, functions, and applications of an extract of Xanthoceras sorbifolia and compounds isolated from the extract, as well as methods for their preparation. It also provides methods and processes for isolating, purifying, and identifying biologically active compounds from Xanthoceras sorbifolia. The patent also provides a composition containing compounds purified from Xanthoceras sorbifolia. Among the compounds purified from Xanthoceras sorbifolia are saponin compounds. The composition can be used to fight cancer, prevent brain aging, enhance memory, improve brain function, treat nocturia, frequent urination, urgency, mental retardation, dementia and Alzheimer's disease, autism, brain trauma, Parkinson's disease, and other conditions caused by impaired or blocked brain function. It can also be used to treat arthritis, rheumatism, poor circulation, arteriosclerosis, Raynaud's disease, angina pectoris, cardiac dysfunction, coronary heart disease, headache, dizziness, renal dysfunction, impotence, and premature ejaculation. However, it primarily describes the effects of the Xanthoceras sorbifolia extract, lacks research on the combination of the Xanthoceras sorbifolia extract with other ingredients, and thus fails to fully demonstrate the efficacy of Xanthoceras sorbifolia oil.

[0005] Huang Yuguang et al. mentioned in their study (Nutrition and Comprehensive Processing of Xanthoceras sorbifolia [J]. Food Research and Development, 2004, 25(3):73-76.) that Xanthoceras sorbifolia oil can be fortified with vitamin E at 0.01% by weight of the oil and used as a seasoning oil; however, no effective components were compounded to fully exert the effect of Xanthoceras sorbifolia oil in improving memory.

[0006] CN110038018A provides a method for preparing a brain neurotrophic therapeutic composition, relating to the field of oil synthesis, the invention uses fatty acid triglycerides, conjugated linoleic acid glycerides and plant sterols as raw materials, and carries out ester exchange reaction with 435 lipase, IM lipase and DF15 lipase, after cooling, decolorization, deodorization, distillation and fine filtration, and then emulsification, embedding, spray drying to obtain a dry powder, and then the dry powder is mixed with phosphatidylserine, N-acetylneuraminic acid, β-hydroxy β-methylbutyrate calcium, konjac glucomannan, mangosteen extract, elderberry and yeast β-glucan, and homogenized to obtain a medium-chain structure lipid composition. The process is simple, convenient and inexpensive, and can prepare accurate nutrition suitable for clinical rehabilitation of diseases such as stroke, Alzheimer's disease, depression, Parkinson's disease and epilepsy. Although it effectively alleviates nerve damage caused by brain trauma and stroke, it uses a variety of raw materials for compounding, and the process is relatively complicated, which brings difficulties to the production and application of the composition.

[0007] Therefore, how to provide a composition that can fully exert the effect of Xanthoceras sorbifolia oil in improving memory through compounding while ensuring that the formula of the composition is relatively concise is one of the important issues studied in this field.

[0008] Summary of the Invention

[0009] The present invention addresses the problems in the prior art that there are few types of Xanthoceras sorbifolia oil-DHA compositions and their formulas are complex, and the effect of Xanthoceras sorbifolia oil in improving memory cannot be fully exerted. The present invention provides a Xanthoceras sorbifolia composition, which has good memory-improving efficacy through compounding with DHA. It is also found that the composition provided by the present invention can significantly improve tic disorders and is significantly better than the effect of using Xanthoceras sorbifolia oil and DHA independently.

[0010] To achieve the above object, the technical solution adopted by the present invention is as follows:

[0011] A Xanthoceras sorbifolia oil DHA composition, consisting of the following components in parts by weight:

[0012] 10-90 parts of Xanthoceras sorbifolia oil, 10-90 parts of DHA.

[0013] Preferably, the Xanthoceras sorbifolia oil DHA composition is composed of the following components in parts by weight:

[0014] Xanthoceras sorbifolia oil 40-60 parts and DHA 40-60 parts.

[0015] Further preferably, the Xanthoceras sorbifolia oil DHA composition is composed of the following components in parts by weight:

[0016] Xanthoceras sorbifolia oil 50-55 parts and DHA 45-55 parts.

[0017] Most preferably, the Xanthoceras sorbifolia oil DHA composition is composed of the following components in parts by weight:

[0018] 50 parts of Xanthoceras sorbifolia oil and 50 parts of DHA.

[0019] Preferably, the Xanthoceras sorbifolia oil includes an oil product extracted from Xanthoceras sorbifolia kernels by mechanical extraction, leaching, aqueous solution extraction, ultrasonic-assisted extraction, supercritical CO2 extraction or aqueous enzyme extraction.

[0020] Preferably, the amount of DHA is calculated based on pure DHA, and the DHA is in the form of an edible product with a DHA content of greater than 50% by mass.

[0021] The present invention also provides the use of the Xanthoceras sorbifolia oil DHA composition in preparing a health product with the function of assisting in improving memory.

[0022] The present invention also provides the use of the Xanthoceras sorbifolia oil DHA composition in the preparation of a medicine having the effects of improving memory and tic disorders.

[0023] The present invention also provides a health product with the function of assisting in improving memory, comprising the Xanthoceras sorbifolia oil DHA composition.

[0024] The present invention also provides a medicine having the effects of improving memory and tic disorders, comprising the above-mentioned Xanthoceras sorbifolia oil DHA composition.

[0025] Preferably, the drug having the effect of improving memory and tic disorders further comprises a pharmaceutically acceptable excipient.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] The present invention significantly improves the effects of Xanthoceras sorbifolia oil and DHA in improving memory and tic disorders by compounding Xanthoceras sorbifolia oil with DHA, compared with the independent use of Xanthoceras sorbifolia oil and DHA. Compared with the existing technology, the Xanthoceras sorbifolia oil DHA composition provided by the present invention has a more concise formula and can effectively improve memory and tic disorders. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] FIG1 shows the results of the central area residence time of rats in Experimental Example 1;

[0029] In Figure 1: **** P < 0.0001 vs CON; # P<0.05vsMOD.

[0030] FIG2 is a graph showing the stereotypic behavior scores of rats in Experimental Example 2;

[0031] FIG3 is a graph showing the motor behavior scores of rats in Experimental Example 2;

[0032] In Figures 2 and 3: ** P < 0.01 vs control group; # P < 0.05 vs model group; ## P < 0.01 vs model group; @ P < 0.05 vs DHA group; & P<0.05vs Xanthoceras sorbifolia oil group. DETAILED DESCRIPTION

[0033] The present invention will be further described in detail below with reference to specific examples. The following examples are not intended to limit the present invention but are merely intended to illustrate the present invention. The experimental methods used in the following examples are generally based on conventional conditions unless otherwise specified. The materials and reagents used in the following examples are all commercially available unless otherwise specified.

[0034] The following raw material sources are illustrative:

[0035] DHA (Batch No. 0523003, Shandong Yuwang Pharmaceutical Co., Ltd.)

[0036] Xanthoceras sorbifolia oil (Batch No. 20220701, Shenzhen Jizhi Bencao Biopharmaceutical Co., Ltd.)

[0037] Scopolamine hydrobromide (Batch No.: J2129103, Aladdin)

[0038] Donepezil hydrochloride (Batch No. 02230150, Plant Biotechnology Co., Ltd.)

[0039] 0.9% sodium chloride injection (Batch number: 220818501, Guangdong Daxiang Pharmaceutical Co., Ltd.)

[0040] Iminodipropionitrile (IDPN, Shanghai MacLean Biochemical Technology Co., Ltd.)

[0041] Example 1 A Xanthoceras sorbifolia oil DHA composition

[0042] The composition was prepared by mixing 50 parts of Xanthoceras sorbifolia oil and 50 parts of DHA and directly mixing them.

[0043] Example 2 A Xanthoceras sorbifolia oil DHA composition

[0044] The composition was prepared by mixing 90 parts of Xanthoceras sorbifolia oil and 10 parts of DHA and directly mixing.

[0045] Example 3 A Xanthoceras sorbifolia oil DHA composition

[0046] The composition was prepared by mixing 10 parts of Xanthoceras sorbifolia oil and 90 parts of DHA and directly mixing.

[0047] Experimental Example 1 Experiment on improving learning and memory in rats

[0048] 1.1 Experimental animals

[0049] Sixty-four healthy SPF male SD rats (40-60 g), aged 19-21 days, were purchased from the Guangdong Medical Laboratory Animal Center. The animals were housed at a temperature of 18-23°C and a relative humidity of 45%-55% with free access to food and water for three days of acclimatization.

[0050] 1.2 Experimental instruments

[0051] Morris water maze system (Guangzhou Bit Biotechnology Co., Ltd.)

[0052] Open field experimental system (Anhui Zhenghua Biological Equipment Co., Ltd.)

[0053] The data were analyzed using video tracking software (SMART 3.0)

[0054] 2 Experimental methods

[0055] 2.1 Animal grouping and drug administration

[0056] 64 SPF male rats (40-60g) were adaptively fed for three days and randomly divided into six groups according to body weight, namely blank control group (CON), model group (MOD), positive drug donepezil group (DNPQ), Xanthoceras sorbifolia oil group (WGG), (DHA) group and Example 1 group (DW1), Example 2 group (DW2), Example 3 group (DW3), 8 rats in each group. CON group and MOD group were gavage-administered with equivalent volume of distilled water, DNPQ group rats were given donepezil at 0.52mg / kg / d, WGG group and DHA group were given Xanthoceras sorbifolia oil and DHA at 31.5mg / kg / d, respectively, and DW1, DW2 and DW3 groups were given Xanthoceras sorbifolia oil DHA composition of the corresponding example at 31.5mg / kg / d. The drugs were administered at a fixed time every day for 30 consecutive days. After 18 days of administration, the learning and memory improvement model was established. Thirty minutes after drug administration each day, rats in all groups except the CON group received an intraperitoneal injection of scopolamine (3 mg / kg / d) in normal saline. Rats in the CON group were injected with an equal volume of normal saline for 12 consecutive days. Behavioral experiments were initiated 30 minutes after modeling, and the successful replication of the model was evaluated based on the results of these behavioral experiments.

[0057] 2.2 Behavioral testing

[0058] Behavioral tests include water maze and open field tests to detect rats' learning and memory abilities.

[0059] 2.2.1 Morris water maze test

[0060] The Morris water maze is used to assess learning and memory in rats. The water maze can provide numerous indicators, the most commonly used being escape latency in the navigation test and the number of platform crossings in the spatial exploration test. The Morris test apparatus consists of a cylindrical pool with a diameter of 150 cm and a height of 50 cm. The interior is divided into four equal quadrants. A platform is placed in the center of one quadrant; once fixed, this platform's position remains unchanged throughout the behavioral test. Two perpendicular lines drawn through the center of the pool divide the pool into four quadrants: northwest, northeast, southeast, and southwest, designated as quadrants I, II, III, and IV, respectively. Markers of different colors and shapes, such as circles, triangles, stars, and squares, are affixed to the inner walls of each quadrant to facilitate memory. The water temperature was maintained at 22 ± 2°C during the experiment. During behavioral testing, the rats' swimming activities were recorded by a camera mounted above the water maze pool. The data were processed using an image acquisition device and behavioral software and stored on a computer.

[0061] Morris water maze experiment content:

[0062] A. Adaptation training: One day before the experiment, water was placed in the water maze without a platform, and rats were trained to adapt to the water maze. Each rat underwent adaptation training for 1 to 2 minutes, and then the rats were taken out and dried.

[0063] B. Spatial Exploration Experiment: On the 12th day of modeling, the platform was removed and the rats were placed in the water from a fixed entry point (diagonally opposite the platform) facing the pool wall. The rats were allowed to explore freely for 90 seconds. The proportion of time they spent swimming in the quadrant where the original platform was located and the number of times they crossed the original platform location (i.e., the number of shuttles) were measured to reflect the rats' spatial memory ability. The more times the rats crossed the original platform location and the longer they stayed in the target quadrant, the stronger their spatial memory ability was.

[0064] 2.2.2 Open field experiment

[0065] The open field test was performed on the second day of modeling. Before the test, the shooting screen was adjusted so that the open field area could be fully displayed on the computer program. At the beginning of the test, the camera program was turned on, the observation time was set to 5 minutes, and the rat was gently placed in the center area of ​​the open field. The free movement trajectory of the rat in the open field, the movement distance in the central area, the total movement distance in the open field, the movement trajectory in the open field box, and the time spent in the peripheral and central areas were recorded. The data were analyzed by video tracking software (SMART3.0). After each rat was tested, 75% medical alcohol was used to spray the plastic box to thoroughly remove the dirt in the box and minimize the odor of feces in the box to prevent residual odor or dirt from affecting the activity of the next rat.

[0066] 2.3 Statistical analysis

[0067] SPSS 25.0 statistical software was used to analyze the data, and the results were expressed as mean ± standard deviation. Graphs were generated using GraphPad Prism 9.0. Intergroup comparisons were performed using the independent sample t-test, multiple group means were compared using one-way analysis of variance, and pairwise comparisons were performed using LSD. P < 0.05 was considered statistically significant, and P < 0.01 was considered highly statistically significant.

[0068] 3 Behavioral Experimental Results

[0069] 3.1 Open field test results

[0070] As shown in Figure 1, in the open field test, the central area time of the rats in the model group showed significant or extremely significant changes compared with the normal rats, indicating that the latency of the scopolamine-administered model group was higher than that of the other groups, indicating that the learning and memory disorder model was successfully established.

[0071] Compared with the CON group, the MOD group showed a significant difference in central zone time (P<0.0001). Compared with the MOD group, central zone time in the DW1, DW2, and DW3 groups was significantly increased (P<0.05), and central zone time in the DHA and WGG groups was lower than that in the DW, DW2, and DW3 groups. This suggests that donepezil, Xanthoceras sorbifolia oil, DHA, and DW combinations all have certain effects on improving learning and memory, and the Xanthoceras sorbifolia oil-DHA combination is more effective in improving learning and memory in young mice than either Xanthoceras sorbifolia oil or DHA alone.

[0072] 3.2 Space exploration experiment results

[0073] (1) Space exploration experiment results

[0074] Table 1 shows the frequency statistics of the number of times the rats in each group crossed the platform in the spatial exploration experiment. It can be seen from the table that the frequency of the rats in the CON group crossing the platform was concentrated between 3 and 4 times, and the frequency of the rats in the MOD group crossing the platform was concentrated between 0 and 2 times. In comparison, the number of times the rats in the MOD group crossed the platform was significantly reduced, which indicates that the rats after scopolamine intervention had poorer ability in learning and memory, which further confirms the successful modeling of this experiment; compared with the MOD group, the number of times the rats in the DNPQ group, DW1 group, DW2 group, DW3 group, WGG group and DHA group crossed the platform was more than that in the MOD group, which indicates that the positive drug, compound, Xanthoceras sorbifolia oil and DHA all have the effect of improving learning and memory. The frequency of rats crossing the platform in groups DW1, DW2 and DW3 was concentrated between 1 and 3 times, and that in group DW2 could even reach 4 times. The frequency of rats crossing the platform in group DNPQ was concentrated between 2 and 4 times. The frequency of rats crossing the platform more than 2 times in groups DW1, DW2 and DW3 was more than that in the groups taking DHA or Xanthoceras sorbifolia oil alone. This indicates that both the compound and donepezil have the effect of improving learning and memory, and the effect of the compound is better than that of taking DHA or Xanthoceras sorbifolia oil alone.

[0075] Table 1 Statistics of the frequency of crossing platforms in each group

[0076] 4 Summary

[0077] This study used young SD rats to investigate the effects of a combination of Xanthoceras sorbifolia oil and DHA on their learning and memory. The results showed that Xanthoceras sorbifolia oil, DHA, and the combination improved learning and memory in young rats, with the combination being more effective than either DHA or Xanthoceras sorbifolia oil alone.

[0078] Experimental Example 2: Efficacy Experiment on Improving Tic Disorder in Rats

[0079] 1. Experimental Animals

[0080] Fifty-six 3-week-old SPF male SD rats weighing 40-60 g were provided by the Guangdong Provincial Laboratory Animal Center. All experimental animals were housed in an SPF-grade barrier animal room at a temperature of 20-25°C and a humidity of 50%-70%.

[0081] 2. Animal Grouping and Model Construction

[0082] After one week of adaptive feeding, the animals were randomly divided into 7 groups (8 in each group): blank group, model group, DHA group (250 mg / kg / day), Xanthoceras sorbifolia oil group (250 mg / kg / day), Example 1 group, Example 2 group and Example 3 group (Example 1-3 groups were all dosed at a mass dosage of 1:1, totaling 250 mg / kg / day). The oral dose was adjusted in time according to the weight of the rats, once a day, for 14 consecutive days. The corresponding drugs were first given continuously for 7 days, and the model was established from the 8th day. 30 minutes after the administration, the blank control group was intraperitoneally injected with 0.9% sodium chloride solution, and the remaining groups were intraperitoneally injected with iminodipropionitrile (IDPN) at a dose of 150 mg / kg, once a day, for 7 consecutive days.

[0083] 3. Assessment of Motor and Stereotyped Behaviors

[0084] Behavioral observations began 30 minutes after modeling on the 14th day of gavage (seven days after modeling). In a quiet, dark environment, mice were removed from their home cages and placed in observation cages. After acclimation, digital video recordings were initiated, with intervals of 5 minutes for 30 minutes. The mice were observed for twitching and rotating dance-like movements of the head and neck, as well as the number of involuntary rotations. Behavioral scores were scored using the Kadasah SA / Diamond scale, with a score of 1 or higher considered a successful model. Observations were conducted double-blind to avoid subjective assumptions that could influence the experimental results. After testing, the observation cages were cleaned of excrement to eliminate any potential impact on the next group of mice.

[0085] The scoring criteria are as follows:

[0086] The results of motor behavior and stereotyped behavior evaluation are shown in Figures 2 and 3. As shown in Figures 2 and 3, compared with the blank group, the motor behavior and stereotyped behavior scores of the model group were significantly increased (P < 0.01), indicating that the head twitching model induced by IDPN in rats was successful. After 14 days of drug intervention treatment, compared with the model group, the motor behavior and stereotyped behavior scores of the Xanthoceras sorbifolia oil group, the DHA group, the Example 1 group, the Example 2 group, and the Example 3 group were significantly decreased (P < 0.05), indicating that each drug-treated group can significantly improve the tic behavior of rats. Compared with the DHA group and the Xanthoceras sorbifolia oil group, the motor behavior and stereotyped behavior scores of the Example 1 group, the Example 2 group, and the Example 3 group were further significantly reduced (P < 0.05), indicating that there is an interaction between DHA and Xanthoceras sorbifolia oil, which can significantly improve tic disorders.

[0087] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A Xanthoceras sorbifolia oil DHA composition, characterized in that: It is composed of the following components in parts by weight: Xanthoceras sorbifolia oil 10-90 parts and DHA 10-90 parts.

2. The Xanthoceras sorbifolia oil DHA composition according to claim 1, characterized in that: It is composed of the following components in parts by weight: 40-60 parts of Xanthoceras sorbifolia oil and 40-60 parts of DHA.

3. The Xanthoceras sorbifolia oil DHA composition according to claim 2, characterized in that: It is composed of the following components in parts by weight: 50 parts of Xanthoceras sorbifolia oil and 50 parts of DHA.

4. The Xanthoceras sorbifolia oil DHA composition according to any one of claims 1 to 3, characterized in that: The Xanthoceras sorbifolia oil includes an oil product obtained by mechanical extraction, leaching, aqueous solution extraction, ultrasonic-assisted extraction, supercritical CO2 extraction or aqueous enzyme extraction of Xanthoceras sorbifolia kernels.

5. The Xanthoceras sorbifolia oil DHA composition according to claim 4, characterized in that: The amount of DHA is calculated based on pure DHA, and the DHA is in the form of an edible product with a DHA mass content greater than 50%.

6. Use of the Xanthoceras sorbifolia oil DHA composition according to any one of claims 1 to 4 in the preparation of a health product with the function of assisting in improving memory.

7. Use of the Xanthoceras sorbifolia oil DHA composition according to any one of claims 1 to 4 in the preparation of a medicament for improving memory and / or tic disorders.

8. A health product with the function of assisting in improving memory, characterized in that: The invention comprises the Xanthoceras sorbifolia oil DHA composition according to any one of claims 1 to 4.

9. A drug having the effect of improving memory and / or tic disorders, characterized in that: The invention comprises the Xanthoceras sorbifolia oil DHA composition according to any one of claims 1 to 4.

10. The drug according to claim 9, characterized in that: Also contains pharmaceutically acceptable excipients.

Images