A composition for improving microcirculation in the pet's brain and nourishing nerves, its preparation method and application.

Abstract

This invention discloses a composition for improving microcirculation in the pet's brain and nourishing nerves, its preparation method, and its application. Belonging to the field of pet medical technology, it specifically relates to a composition for improving microcirculation in the pet's brain and nourishing nerves, comprising: 2-5 parts of Ginkgo biloba extract, 10-20 parts of curcumin, 5-10 parts of α-lipoic acid, 75-125 parts of Astragalus polysaccharide, 0.5-5 parts of vitamin B12, and 0.25-2 parts of vitamin B1. This invention scientifically combines Ginkgo biloba extract, curcumin, α-lipoic acid, Astragalus polysaccharide, vitamin B1, and vitamin B12, utilizing the synergistic effects of each component in anti-inflammatory, antioxidant, microcirculation improvement, and neurotrophic effects, to provide a composition that can effectively improve microcirculation in the pet's brain and nourish nerves, filling a gap in the prior art.

Description

Technical Field

[0001] This invention belongs to the field of pet medicine technology, and in particular relates to a composition that improves microcirculation in the pet's brain and nourishes the nerves, as well as its preparation method and application. Background Technology

[0002] With the continuous increase in pet ownership and the extension of pet lifespan, the incidence of neurological diseases in older pets is showing a significant upward trend. Epidemiological data shows that neurological diseases account for a considerable proportion of veterinary clinical cases. For example, French Bulldogs often present with neurological symptoms, and many referred cases are diagnosed with neurological diseases. These diseases seriously affect the quality of life of affected animals, often leading to progressive sexual dysfunction, behavioral abnormalities, and even endangering their lives.

[0003] Common brain diseases in pets include cerebrovascular accidents (stroke), cognitive impairment syndromes (similar to Alzheimer's disease in humans), encephalitis, and neurodegenerative diseases caused by various reasons. Although the causes of these diseases differ, their pathophysiological processes share common characteristics: impaired cerebral microcirculation, persistent neuroinflammatory responses, oxidative stress damage, and disordered neuronal energy metabolism. After a stroke, neurons in the ischemic core area die rapidly due to interrupted blood flow, while the surrounding penumbra region faces secondary damage from ischemia-reperfusion injury, cytokine storms, and microcirculatory disturbances. For degenerative diseases such as cognitive impairment, chronic neuroinflammation and excessive activation of microglia are considered key mechanisms driving pathological progression.

[0004] Currently, clinical treatments for pet brain diseases mainly include the following categories: anti-inflammatory drug therapy, with glucocorticoids (such as prednisolone) being the first-line treatment for non-infectious inflammatory neurological diseases. However, long-term use of glucocorticoids is often accompanied by serious side effects, including gastrointestinal ulcers, iatrogenic hyperadrenocorticism, liver disease, and hair loss. Other immunosuppressants such as cytarabine, cyclosporine, and mycophenolate mofetil can be used as adjunctive therapy, but they carry risks such as bone marrow suppression, hepatotoxicity, and nephrotoxicity. Neurotrophic and metabolic support drugs, such as B vitamins (such as vitamin B1 and B12), coenzyme Q10, and levocarnitine, are commonly used clinically as adjunctive therapy to improve nerve cell energy metabolism and promote myelin repair. However, these components often have limited efficacy when used alone due to low absorption rates, insufficient targeting, or single pathways of action. Drugs that improve cerebral circulation, while having some application in improving microcirculation, have limited efficacy as single-drug formulations and are insufficient to comprehensively address the complex pathological processes of brain diseases. Physical therapy and rehabilitation methods, such as laser therapy, have been used in neurological rehabilitation in recent years to support nerve recovery by improving mitochondrial ATP production and reducing oxidative stress. However, their application requires specialized equipment and multiple treatments, limiting their widespread use. Cutting-edge cell and gene therapies, such as stem cell therapy (e.g., mesenchymal stem cells) and gene reprogramming technologies (e.g., NeuroD1-mediated reprogramming of astrocytes into neurons), have shown potential for anti-inflammatory effects and promoting functional recovery in animal models. However, these technologies are still in the research stage and face challenges such as low cell survival rates, tumorigenicity risks, immune rejection, ethical controversies, and high translational costs, preventing their widespread application in clinical pet treatment.

[0005] The shortcomings of existing technologies can be summarized in the following aspects: First, they target only a single pathological process. Most existing drugs target only a single pathological step, while brain diseases involve multiple interrelated pathological processes such as inflammation, microcirculatory disturbances, oxidative stress, and nerve damage. Single-target intervention is unlikely to achieve ideal therapeutic effects. Second, they have significant side effects, especially long-term use of glucocorticoids and immunosuppressants, which burden multiple organ systems in pets and limit their long-term use. Third, they have low bioavailability. Some natural active ingredients with neuroprotective potential (such as curcumin) have low bioavailability when used alone due to poor water solubility, rapid metabolism, and difficulty crossing the blood-brain barrier, making it difficult to exert their intended therapeutic effects. Fourth, existing technologies mostly use single components or simple combinations, lacking a systemic design based on multiple targets and pathways, and failing to fully utilize the synergistic effects between different components. It is worth noting that recent research on human brain diseases has increasingly emphasized multi-target combined intervention strategies. For example, a combination of PEA and luteolin has shown effects in improving neurological function and cognitive prognosis in patients with acute ischemic stroke. This suggests that by rationally combining functional components with different mechanisms of action, it may be possible to achieve a more comprehensive and effective intervention in brain diseases.

[0006] However, for pets, a compound preparation that combines anti-inflammatory, microcirculation-improving, and neurotrophic effects while maintaining high safety and suitability for long-term use is currently lacking. Based on the pathological characteristics of pet neurological diseases, it is necessary to develop a composition with a clear mechanism of action, synergistic effects among its components, and high bioavailability to meet clinical needs for treating pet brain degeneration, inflammatory responses, and post-stroke diseases. Summary of the Invention

[0007] To address the aforementioned technical problems, this invention proposes a composition that improves microcirculation in the pet's brain and nourishes nerves, along with its preparation method and application. This invention scientifically combines ginkgo biloba extract, curcumin, α-lipoic acid, astragalus polysaccharide, vitamin B1, and vitamin B12, utilizing the synergistic effects of each component in anti-inflammatory, antioxidant, microcirculation improvement, and neurotrophic properties to provide a composition that effectively improves microcirculation in the pet's brain and nourishes nerves, filling a gap in the existing technology.

[0008] To achieve the above objectives, the present invention provides a composition for improving microcirculation in the brain and nourishing nerves in pets, comprising the following components in parts by weight: 2-5 parts of Ginkgo biloba extract, 10-20 parts of curcumin, 5-10 parts of α-lipoic acid, 75-125 parts of Astragalus polysaccharide, 0.5-5 parts of vitamin B12, and 0.25-2 parts of vitamin B1.

[0009] Preferably, the composition includes the following components in parts by weight: 3.5 parts of Ginkgo biloba extract, 15 parts of curcumin, 7.5 parts of alpha-lipoic acid, 100 parts of astragalus polysaccharide, 2.625 parts of vitamin B12, and 1.125 parts of vitamin B1.

[0010] Ginkgo biloba extract: It is good at dilating cerebral blood vessels, reducing blood viscosity, improving microcirculation, and inhibiting platelet-activating factor (PAF), thus opening up channels for hypoxic brain tissue.

[0011] Curcumin: It mainly blocks the release of inflammatory factors by inhibiting the nuclear factor κB pathway and inhibits the excessive activation of microglia.

[0012] Alpha-lipoic acid: a powerful antioxidant that is soluble in both water and oil. It can penetrate the blood-brain barrier and directly eliminate free radicals generated by ischemia-reperfusion injury.

[0013] Astragalus polysaccharides: have immunomodulatory effects, which can not only enhance immunity, but also help regulate immune balance and promote the repair of damaged tissues in the later stages of inflammation.

[0014] Vitamin B12: It participates in the synthesis and repair of myelin sheath (the protective layer of nerve fibers), which is crucial for the recovery of conduction function of damaged nerves after cerebral infarction.

[0015] Vitamin B1 is a key coenzyme in glucose metabolism. The brain mainly relies on glucose for energy, and sufficient vitamin B1 can ensure the energy supply to brain cells.

[0016] The present invention also provides a method for preparing the composition, comprising the following steps: weighing ginkgo leaf extract, curcumin, α-lipoic acid, astragalus polysaccharide, vitamin B12 and vitamin B1 according to the weight parts, mixing them to obtain the composition.

[0017] The present invention also provides the use of the composition in the preparation of a medicament for treating inflammatory responses in the brain of pets.

[0018] Preferably, the composition inhibits neuroinflammation by scavenging free radicals generated by ischemia-reperfusion injury, blocking the release of inflammatory factors, enhancing the body's own antioxidant capacity, and suppressing neuroinflammation.

[0019] The present invention also provides the use of the composition in the preparation of a medicament for pets to assist in the repair of brain degeneration and post-stroke brain injury.

[0020] Preferably, the composition improves cerebral microcirculation, inhibits neuroinflammation, regulates the body's immune function, nourishes nerves, and assists in the repair of brain degeneration and post-stroke brain damage.

[0021] The present invention also provides the use of the composition in the preparation of a medicament for improving microcirculation in the pet brain and nourishing the nerves.

[0022] Compared with the prior art, the present invention has the following advantages and technical effects: This invention provides a composition for improving microcirculation in the pet's brain and nourishing nerves, its preparation method, and its application. Alpha-lipoic acid can recycle other antioxidants in the body, indirectly enhancing the antioxidant persistence of Ginkgo biloba extract in vivo. Curcumin blocks the release of inflammatory factors, while alpha-lipoic acid enhances the body's own antioxidant defense system. The antioxidant environment induced by alpha-lipoic acid can reduce cellular stress, allowing curcumin to focus more on regulating immunity and anti-inflammation. The combination of the two can more comprehensively inhibit neuroinflammation. Astragalus polysaccharides protect neurons through antioxidant and anti-apoptotic effects, while curcumin inhibits excessive microglial cell activity. The two work together to reduce secondary damage to neurons; α-lipoic acid has antioxidant properties and can also increase intracellular glutathione levels, protecting the activity of vitamin B12 and vitamin B2 in the body, while improving insulin sensitivity and helping brain cells better utilize glucose; Ginkgo biloba extract improves cerebral blood flow, meaning more blood is delivered to damaged brain areas. Vitamin B12 absorption and utilization decreases in hypoxic environments, but ginkgo improves microcirculatory hypoxia, increasing the bioavailability of vitamin B12, thereby better repairing myelin and improving cognitive function and motor coordination. In summary, the composition of this invention follows the principles of pathway complementarity and target synergy, cutting off inflammation at two sources: transcription factors and oxidative stress. On the one hand, it unblocks blood supply; on the other hand, it protects vascular endothelium from oxidative damage, providing energy, repairing myelin, and regulating the immune microenvironment to promote repair. Attached Figure Description

[0023] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0024] Figure 1 The scores for the degree of modified neurological deficit in each group of mice in Experiment 1 were statistically analyzed. Figure 2 The percentage of left-right swings in each group of mice in Experiment Example 1 out of the total number of swings; Figure 3 The time that the mice in each group spent on the rotarod in Experiment Example 1; Figure 4 The results of SOD activity assay in the serum of mice in each group in Experiment Example 1; Figure 5 The results of GSH level measurement in the serum of mice in each group in Experiment Example 1; Figure 6 The results show the MDA levels in the serum of mice in each group in Experiment Example 1. Detailed Implementation

[0025] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0026] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Every smaller range between any stated value or intermediate value within a stated range, and any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0027] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0028] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0029] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0030] Unless otherwise specified, the term "parts" in this invention refers to parts by weight.

[0031] The ginkgo leaf extract used in this invention was purchased from Shanghai Yuanye Biotechnology Co., Ltd.

[0032] Example 1 The following ingredients were weighed according to their weight proportions: 3.5 parts ginkgo leaf extract, 15 parts curcumin, 7.5 parts α-lipoic acid, 100 parts astragalus polysaccharide, 2.625 parts vitamin B12, and 1.125 parts vitamin B1. The mixture was then prepared to obtain the composition.

[0033] Example 2 Two parts of ginkgo leaf extract, ten parts of curcumin, five parts of α-lipoic acid, seventy-five parts of astragalus polysaccharide, 0.5 parts of vitamin B12, and 0.25 parts of vitamin B1 were weighed according to their weight proportions and mixed to obtain the composition.

[0034] Example 3 The following ingredients were weighed according to their weight proportions: 5 parts ginkgo leaf extract, 20 parts curcumin, 10 parts α-lipoic acid, 125 parts astragalus polysaccharide, 5 parts vitamin B12, and 2 parts vitamin B1. The mixture was then prepared to obtain the composition.

[0035] Comparative Example 1 Ginkgo biloba extract 3.5 parts, curcumin 22.5 parts, astragalus polysaccharide 100 parts, vitamin B12 2.625 parts, vitamin B1 1.125 parts. Weigh out the ginkgo biloba extract, curcumin, α-lipoic acid, astragalus polysaccharide, vitamin B12 and vitamin B1 according to the weight parts, mix them, and the resulting mixture is the modified composition one.

[0036] Comparative Example 2 Ginkgo biloba extract (10 parts), curcumin (5 parts), α-lipoic acid (7.5 parts), astragalus polysaccharide (150 parts), vitamin B12 (0.1 parts), and vitamin B1 (3 parts) are weighed according to their weight proportions and mixed to obtain the second modified formula composition.

[0037] Experimental Example 1 One hundred and forty SPF-grade male ICR mice, weighing 25–30 g, were used as experimental animals. The animals were housed in a temperature- and humidity-controlled environment with free access to food and water, maintaining a 12-hour light / 12-hour dark cycle. They were divided into seven groups of twenty mice each: sham-operated group, saline group, Example 1 group, Example 2 group, Example 3 group, Comparative Example 1 group, and Comparative Example 2 group. Mice in the saline group, Example 1 group, Example 2 group, Example 3 group, Comparative Example 1 group, and Comparative Example 2 group underwent a 90-minute transient middle cerebral artery occlusion (tMCAO) procedure to induce focal ischemic brain injury, followed immediately by tMCAO reperfusion. Mice in the sham-operated group received no treatment except for making the same incision at the same site. Following tMCAO reperfusion, mice in Examples 1, 2, 3, Comparative Example 1, and 2 were given the first dose of the following formulations: The compositions prepared in Example 1, Example 2, Example 3, Modified Composition 1 of Comparative Example 1, and Modified Composition 2 of Comparative Example 2 were dissolved in physiological saline at a dose of 129.75 mg / kg / day and administered intraperitoneally to the corresponding groups of mice. Subsequent administration was once daily. The sham-operated group and the saline group received an equal volume of physiological saline intraperitoneally once daily.

[0038] Three days prior to surgery, mice underwent rotarod acclimatization training. Mice were placed on a fatigue rotarod and subjected to a 5-minute, 5-minute acceleration from rest to 40 rpm. Training was conducted three times daily, with 5-minute rest periods between rounds. Mice unable to learn the rotarod behavior were eliminated during training. The time spent on the rotarod (accelerating from rest to 20 rpm) was measured on day 1 before surgery and on days 1, 3, 7, and 14 post-surgery. Modified neurological deficit scores were also assessed on days 1, 3, 7, and 14 post-surgery. A body-lifting and rocking test was performed on days 1, 3, 7, and 14 post-surgery to assess the recovery of muscle strength and balance. Mice were euthanized under deep anesthesia after the experiment.

[0039] Modified Neurological Deficit Score (mNSS): The degree of neurological impairment in mice was assessed using the modified neurological deficit score (mNSS). The score range was 0-14 points, where 0 points represented normal function and 14 points represented the most severe functional deficit. The scoring covered the following three aspects: (1) Motor function test: Observe the flexion of the forelimbs and hindlimbs by suspending the mouse by its tail (0-3 points); Observe gait abnormalities by placing the mouse on a flat surface (0-3 points); (2) Balance test: Observe the mouse's ability to maintain balance and the occurrence of limb slippage by placing it on a balance beam (0-6 points); (3) Reflex test: Check the presence of auricular reflex and corneal reflex (0-2 points). The total score is obtained by adding up the scores of each item.

[0040] Elevated body rocking test: This test assesses the recovery of balance function in mice after brain injury. During the test, the mouse's tail is gently lifted, suspending it approximately 10 cm above the testing platform. The degree of deviation of the mouse's head from the vertical midline is used to determine the rocking motion. A deviation of more than 10° from the vertical midline is counted as one rocking motion; deviations within 10° are considered no rocking motion. A manual counter is used to record the number of left and right head swings, and the percentage of left and right swings is calculated.

[0041] The fatigue rotundus test is used to assess the motor coordination and limb function recovery in mice. The test consists of a training period and a testing period. The training period lasts for 3 days, allowing mice to adapt to walking on a rotundus at a constant speed of 20 rpm. There are 3 rounds of training per day, each round lasting 5 minutes, with a 5-minute rest period between rounds. Mice that fail to learn the behavior are eliminated during this period. In the formal testing, the mouse is placed on the rotundus, and the speed is increased uniformly from rest to 40 rpm and maintained at a constant speed. The time the mouse spends on the rotundus from the start of the test until it falls (or reaches the preset maximum testing time) is recorded as an indicator of motor coordination.

[0042] Blood collection from the eyeballs: The collected blood was placed in centrifuge tubes and incubated at 37°C for 1 hour, then at 4°C overnight. The blood coagulated and separated into layers. The tubes were centrifuged at 2000 rpm for 15 minutes, and the supernatant was collected and stored at -80°C. Serum SOD activity (purchased from Bailingwei), GSH content (purchased from Yisheng Biotechnology), and MDA (purchased from Solarbio) were measured using a kit.

[0043] Table 1. Improved neurological deficit scores for each group of mice

[0044] Table 2. Percentage of left-right swinging motions in each group of mice out of the total number of swinging motions.

[0045] Table 3. Duration of mice in each group on the rotarod

[0046] As shown in Table 1 and Figure 1 As shown in Table 2, the mNSS scores of mice in Examples 1-3 were lower than those in the saline group, while the mNSS scores of mice in Comparative Examples 1-2 were basically consistent with those in the saline group. Figure 2 As shown, the percentage of left-right swinging movements in mice in Examples 1-3 was significantly lower than that in the saline group after day 7. The percentage of left-right swinging movements in mice in Comparative Examples 1-2 was basically consistent with that in the saline group, as shown in Table 3. Figure 3 As shown, the time mice in Examples 1-3 spent on the rotarod after day 3 was significantly longer than that in the saline group. The time mice in Comparative Examples 1-2 spent on the rotarod was essentially the same as that in the saline group. This indicates that the composition of this invention improved the motor coordination of mice as early as 3 days post-surgery and helped restore balance after brain injury. The modified formulations in Comparative Examples 1 and 2, due to the disruption of the synergistic effect between components, showed poor efficacy in restoring brain injury in mice. Tables 1-3 and... Figures 1-3 The experimental data for the sham-operated mice were not included because the sham-operated mice did not suffer brain nerve damage after surgery, and no pathological signs were observed in any vital signs.

[0047] like Figure 4 As shown, the SOD activity in the serum of mice in Examples 1-3 was higher than that in the saline group and the sham-operated group, while the SOD activity in the serum of mice in Comparative Examples 1-2 was basically the same as that in the saline group. Figure 5 As shown, the serum GSH levels in mice in Examples 1-3 were higher than those in the saline group, while the serum GSH levels in Comparative Examples 1-2 were basically consistent with those in the saline group. Figure 6 As shown, the MDA levels in the serum of mice in Examples 1 to 3 were lower than those in the saline group, similar to the sham-operated group. The MDA levels in the serum of mice in Comparative Examples 1 to 2 were basically consistent with those in the saline group. This indicates that the composition of the present invention can improve the body's resistance to oxidative damage and thus reduce inflammatory response. The modified formulations in Comparative Examples 1 and 2, due to the disruption of the compatibility between components, did not have a good effect on improving the body's resistance to oxidative damage.

[0048] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. A composition for improving microcirculation in the pet's brain and nourishing nerves, characterized in that, It includes the following components by weight: 2-5 parts of Ginkgo biloba extract, 10-20 parts of curcumin, 5-10 parts of α-lipoic acid, 75-125 parts of Astragalus polysaccharide, 0.5-5 parts of vitamin B12, and 0.25-2 parts of vitamin B1.

2. The composition according to claim 1, characterized in that, It includes the following components by weight: 3.5 parts ginkgo leaf extract, 15 parts curcumin, 7.5 parts alpha-lipoic acid, 100 parts astragalus polysaccharide, 2.625 parts vitamin B12, and 1.125 parts vitamin B1.

3. The method for preparing the composition according to claim 1 or 2, characterized in that, Includes the following steps: Weigh out the ginkgo leaf extract, curcumin, alpha-lipoic acid, astragalus polysaccharide, vitamin B12 and vitamin B1 according to the weight parts, mix them, and the composition is obtained.

4. Use of the composition of claim 1 or 2 in the preparation of a medicament for treating inflammatory responses of the brain in pets.

5. The application according to claim 4, characterized in that, The composition inhibits neuroinflammation by scavenging free radicals generated by ischemia-reperfusion injury, blocking the release of inflammatory factors, enhancing the body's own antioxidant capacity, and suppressing neuroinflammation.

6. The use of the composition of claim 1 or 2 in the preparation of a medicament for pets to assist in the repair of brain damage and cerebral infarction.

7. The application according to claim 6, characterized in that, The composition improves cerebral microcirculation, inhibits neuroinflammation, regulates the body's immune function, nourishes nerves, and assists in the repair of brain degeneration and brain damage after cerebral infarction.

8. Use of the composition of claim 1 or 2 in the preparation of a medicament for improving microcirculation in the pet brain and nourishing nerves.

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