Compound composition for preventing and treating neurodegenerative diseases as well as preparation method and application of compound composition

Abstract

The invention relates to the technical field of medicines and foods, in particular to a compound composition for preventing and treating neurodegenerative diseases as well as a preparation method and application of the compound composition. The compound composition is prepared from the following components in parts by weight: 10 to 30 parts of astaxanthin, 5 to 15 parts of nervonic acid, 10 to 25 parts of ginkgo flavone and 25 to 50 parts of saponin. According to the composite composition, through the synergistic effect of the astaxanthin, the nervonic acid, the ginkgetin and the saponin, the anti-neuroinflammation and anti-oxidative stress capabilities of the composite composition can be improved, so that the composite composition has good protein homeostasis, anti-neuroinflammation and anti-oxidative stress capabilities.

Description

Technical Field

[0001] The present application relates to the technical field of medicine and food, and in particular to a composite composition for preventing and treating neurodegenerative diseases, and a preparation method and application thereof. Background Art

[0002] Neurodegenerative diseases are diseases caused by abnormal nervous system function, which are mainly manifested by the gradual loss of neuronal structure and function, affecting the patient's memory, movement, language and intelligence. Existing studies have shown that neurodegeneration is the main cause of the gradual loss of neuronal structure and function. The main causes of neurodegeneration include neuronal death and glial cell balance. As neurodegeneration intensifies, cognitive disorders such as dementia will occur. Among other causes of neurodegeneration, age (such as Alzheimer's disease AD, Parkinson's disease PD) or gene mutations that affect the cell function of the central nervous system (CNS) (such as Huntington's disease, early-onset AD or PD, amyotrophic lateral sclerosis ALS) can cause neurodegenerative diseases. In these neurodegenerative diseases, AD is manifested by characteristic protein aggregation in neurofibrillary tangles and plaques, neuronal and glial cell death, and impaired cognitive function caused by aging or gene mutations. In these disease states, characteristic proteins or other stimuli that aggregate in neurofibrillary tangles and plaques can lead to chronic neuroinflammation, which can cause the death of neurons, astrocytes, oligodendrocytes and other cells and even aggravate the progression of neurodegenerative diseases. Current studies have shown that neuroinflammation and oxidative stress are the main influencing factors for the onset of neurodegenerative diseases. Neuroinflammation refers to the pro-inflammatory state after the microglia and astrocytes of the nervous system are activated, which is an important pathological factor of degenerative neurological diseases; while oxidative stress is considered to be a regulatory factor of aging and various nervous system diseases, manifested as increased levels of reactive substances (oxygen, hydroxyl free radicals).

[0003] Neuroinflammation is prone to occur in the CNS under the stimulation of toxic stimuli (such as protein aggregation), infection, traumatic injury or autoimmunity, and the immune system (microglia and macrophages) and astrocytes will try to remove harmful stimuli from the central nervous system to protect brain function, and then this process may become dysfunctional in neurodegenerative diseases. Existing studies have shown that glial cells have anti-inflammatory and pro-inflammatory functions, and participate in various immune functions under normal and diseased conditions (including phagocytosis, elimination of free radicals and cell repair, etc.). At the same time, glial cells are also involved in the establishment of brain circuits and play a key role in synaptic development and synaptic function. In the pro-inflammatory state, glial cells will release pro-inflammatory factors and reactive oxygen species, which will lead to synaptic loss and impaired neuronal function, and even neuronal death. Neuronal death will prompt glial cells to further release pro-inflammatory factors, resulting in more neuronal damage, and ultimately central nervous system damage.

[0004] Based on the above analysis, the risk factors for neurodegenerative diseases are closely related to three factors: protein homeostasis, neuroinflammation, and oxidative stress. Therefore, starting from these factors, we can effectively prevent and reduce the occurrence of neurodegenerative diseases, which is the main idea of ​​neurodegenerative disease treatment and drug development. However, the current drugs for neurodegenerative diseases are temporarily unable to maintain protein homeostasis, avoid neuroinflammation, and resist oxidative stress at the same time. Summary of the invention

[0005] The present application provides a composite composition for preventing and treating neurodegenerative diseases, and a preparation method and application thereof, to solve the following technical problem: how to simultaneously improve the protein homeostasis, anti-neuroinflammation and anti-oxidative stress capabilities of a drug for neurodegenerative diseases.

[0006] In a first aspect, the present application provides a composite composition for preventing and treating neurodegenerative diseases, wherein the composite composition comprises, by weight: 10 to 30 parts of astaxanthin, 5 to 15 parts of neuraminic acid, 10 to 25 parts of ginkgo flavonoids and 25 to 50 parts of saponins.

[0007] Optionally, the saponins include ginsenosides and notoginsenosides.

[0008] Optionally, the weight proportion of the ginsenoside is 20 to 30 parts, and the weight proportion of the notoginsenoside is 5 to 20 parts.

[0009] Optionally, the composite composition further comprises, by weight: 5 to 15 parts of solvent, 1 to 20 parts of co-emulsifier and 10 to 25 parts of emulsifier.

[0010] Optionally, the solvent includes an oily base and / or water;

[0011] The auxiliary emulsifier includes: soybean lecithin and / or modified starch;

[0012] The emulsifiers include Span and / or Tween.

[0013] Optionally, when the solvent comprises an oily base, the oily base comprises at least one of the following: sunflower seed oil, soybean oil, safflower oil, walnut oil and Acer truncatum seed oil.

[0014] In a second aspect, the present application provides a method for preparing the composite composition according to the first aspect, the method comprising:

[0015] Under a first preset vacuum condition, the oily matrix, astaxanthin, nervonic acid and ginkgo flavonoids are first stirred and mixed to obtain a first mixed solution;

[0016] Performing a second stirring mixing on the saponin and the solvent under a second preset vacuum degree to obtain a second mixed solution; and

[0017] The first mixed liquid and the second mixed liquid are combined, and then an emulsifier and an auxiliary emulsifier are added to the combined mixed liquid under the condition of the first preset vacuum degree to perform the first stirring and mixing to obtain a composite composition.

[0018] Optionally, the first stirring and mixing speed is 6500 rpm to 12000 rpm, the first stirring and mixing temperature is 50° C. to 65° C., and the first stirring and mixing time is 10 min to 20 min; and / or

[0019] The second stirring and mixing speed is ≥200 rpm, and the second stirring and mixing time is 10 min to 20 min; and / or

[0020] The first vacuum degree and the second vacuum degree are respectively -0.098 MPa to -0.08 MPa.

[0021] In a third aspect, the present application provides a capsule preparation for preventing and treating neurodegenerative diseases, the capsule preparation comprising the composite composition described in the first aspect, and further comprising, by weight: 50 to 60 parts of gelatin, 20 to 30 parts of glycerol, 1 to 3 parts of caramel color and 50 to 60 parts of solvent.

[0022] In a fourth aspect, the present application provides a method for preparing the capsule preparation according to the third aspect, the method comprising:

[0023] The composite composition, the gelatin, the glycerin, the caramel color and the solvent are heated and stirred to obtain a mixed glue solution;

[0024] Degassing and heat-insulating the mixed glue solution in vacuum to obtain a glue solution product; and

[0025] The colloid product is poured into capsule shells to prepare soft capsules, and then dried to obtain capsule preparations.

[0026] The above technical solution provided by the embodiment of the present application has the following advantages compared with the prior art:

[0027] The embodiments of the present application provide a composite composition for preventing and treating neurodegenerative diseases. The composite composition is based on the antioxidant, anti-inflammatory and anti-apoptotic effects of astaxanthin, and is combined with the characteristics of neuraminic acid in improving the activity of nerve cells and enhancing the signal transmission between nerve cells. It can cooperate with astaxanthin to improve the damage resistance of neurons. In addition, neuraminic acid inhibits the production of β-amyloid protein by regulating the external signal protein kinases and transcription factors of neuronal cells to increase the stability of presynaptic membranes and improve synaptic transmission function, thereby increasing the nerve conduction velocity, improving the cognitive function, memory and learning ability of the brain, and improving the anti-neuroinflammatory ability of the composite composition. In addition, based on the strong Reducing property has a good protective effect on astaxanthin to avoid the premature inactivation of the antioxidant activity of astaxanthin, thereby improving the antioxidant activity of astaxanthin. At the same time, ginkgo flavonoids can also change the aggregation of tau protein and Aβ protein, effectively reduce the toxic effects of Aβ oligomers, so as to improve the antioxidant and anti-neuroinflammatory ability of the composite composition; in addition, based on saponins, it also has antioxidant, anti-inflammatory and neuron-protecting effects, and can be combined with neuraminic acid to further reduce the deposition of Aβ protein and the damage of oxidative stress to neurons, and further improve the anti-neuroinflammation and anti-oxidative stress capabilities of the composite composition; therefore, the composite composition has good protein homeostasis, anti-neuroinflammation and anti-oxidative stress capabilities. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments consistent with the present application and, together with the description, serve to explain the principles of the present application.

[0029] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, for ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative labor.

[0030] Figure 1 A schematic diagram of a product of a composite composition for preventing and treating neurodegenerative diseases is provided for an embodiment of the present application;

[0031] Figure 2 A schematic flow chart of a method for preparing a composite composition for preventing and treating neurodegenerative diseases provided in an embodiment of the present application;

[0032] Figure 3 A schematic flow chart of a method for preparing a capsule preparation provided in an embodiment of the present application. DETAILED DESCRIPTION

[0033] In order to make the purpose, technical solution and advantages of the embodiments of the present application clearer, the technical solution in the embodiments of the present application will be clearly and completely described below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of this application.

[0034] Various embodiments of the present application may be presented in the form of a range; it should be understood that the description in the form of a range is only for convenience and brevity and should not be understood as a rigid limitation on the scope of the present application; therefore, it should be considered that the range description has specifically disclosed all possible sub-ranges and single numerical values ​​within the range; for example, it should be considered that the range description from 1 to 6 has specifically disclosed sub-ranges, such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., as well as single numbers within the range, such as 1, 2, 3, 4, 5 and 6, which applies regardless of the range; in addition, whenever a numerical range is indicated in this document, it is meant to include any cited numbers (fractions or integers) within the indicated range.

[0035] In this document, the terms including "including" and "including" mean "including but not limited to". Relational terms such as "first" and "second" are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. "And / or" describes the association relationship of associated objects, indicating that there can be three relationships. For example, A and / or B can mean: A exists alone, A and B exist at the same time, and B exists alone; where A and B can be singular or plural. "At least one" means one or more, and "plurality" means two or more; "at least one", "at least one of the following" or similar expressions, refers to any combination of these items, including any combination of single or plural items; for example, "at least one of a, b, or c", or "at least one of a, b, and c" can all mean: a, b, c, ab (i.e., a and b), ac, bc, or abc, where a, b, and c can be single or multiple. "Parts" such as parts by weight and parts by mass indicate the proportional relationship between the components. In the proportional relationship involved in this article, the parameters that need to be described by proportion should be understood as the first term of the proportional formula in the order of description, and the proportional numbers should be understood as the second term of the proportional formula. For example, if the mass ratio of substance A, substance B and substance C is 1:2:3, then substance A, substance B and substance C should correspond to the proportional numbers in the proportional formula in the order of description, that is, the mass of substance A: the mass of substance B: the mass of substance C = 1:2:3.

[0036] Unless otherwise specified, various raw materials, reagents, instruments and equipment used in this article can be purchased from the market or prepared by existing methods.

[0037] Figure 1 The product schematic diagram of a composite composition for preventing and treating neurodegenerative diseases provided by an embodiment of the present application is exemplarily shown;

[0038] like Figure 1 As shown, an embodiment of the present application provides a composite composition for preventing and treating neurodegenerative diseases. The composite composition includes, by weight: 10 to 30 parts of astaxanthin, 5 to 15 parts of neuraminic acid, 10 to 25 parts of ginkgo flavonoids and 25 to 50 parts of saponins.

[0039] It should be noted that astaxanthin is a powerful quencher of singlet oxygen and has a strong ability to scavenge oxygen free radicals. It is an extremely effective oxidant. Its antioxidant activity is 550 times that of vitamin E and 10 times that of carotenoids such as β-carotene, zeaxanthin, lutein and canthaxanthin. It is known as "super vitamin E" and "super antioxidant". The weight proportion of astaxanthin can be 10 to 30 parts. Based on the fact that astaxanthin has significant antioxidant stress and anti-inflammatory effects, and the astaxanthin molecule has both hydrophilic and lipophilic groups, the astaxanthin molecule can easily pass through the blood-brain barrier, thereby improving the therapeutic effect of the composite composition on neurodegenerative diseases.

[0040] The weight proportion of the astaxanthin can be 10 parts, 15 parts, 20 parts, 25 parts or 30 parts.

[0041] It should be noted that neuraminic acid (cis-15-tetradecenoic acid, C24:1) is the main long-chain monounsaturated fatty acid in the central nervous system and is the core natural component of brain nerve tissue and nerve cells. Existing studies have shown that neuraminic acid is a substance that promotes the repair and regeneration of damaged nerve tissue, but it is difficult for the human body to synthesize neuraminic acid, and the reduction of neuraminic acid levels is closely related to the high risk of individuals suffering from mental illness. Therefore, supplementing neuraminic acid is a recognized effective method for treating a variety of neurological diseases. The weight proportion of neuraminic acid can be 5 to 15 parts. Through the characteristics of neuraminic acid to increase the activity of nerve cells and enhance the signal transmission between nerve cells, it can cooperate with astaxanthin to improve the resistance of neurons to damage. In addition, neuraminic acid inhibits the production of β-amyloid protein by regulating the external signal protein kinase and transcription factor of neuronal cells, which can increase the nerve conduction velocity to improve the cognitive function, memory and learning ability of the brain, and improve the anti-neuroinflammatory ability of the composite composition.

[0042] The weight parts of the nervonic acid can be 5 parts, 6 parts, 7 parts, 8 parts, 9 parts, 10 parts, 11 parts, 12 parts, 13 parts, 14 parts or 15 parts.

[0043] It should be noted that ginkgo flavonoids have a certain protective effect on cerebrovascular diseases. Existing studies have shown that ginkgo flavonoids can have a significant preventive effect on neurodegenerative diseases caused by cerebrovascular accidents or vascular lesions by scavenging free radicals and inhibiting inflammatory reactions. In addition, ginkgo flavonoids have a promoting effect on the proliferation of neural stem cells and can also promote the transformation of neural stem cells into neurons. The weight proportion of ginkgo flavonoids can be 10 to 25 parts. Based on the strong reducing property of ginkgo flavonoids, it can have a good protective effect on astaxanthin to avoid the premature inactivation of the antioxidant activity of astaxanthin, thereby improving the antioxidant activity of astaxanthin. At the same time, ginkgo flavonoids can also change the aggregation of tau protein and Aβ protein, effectively reduce the toxic effects of Aβ oligomers, so as to improve the antioxidant and anti-neuroinflammatory ability of the composite composition.

[0044] The weight proportions of the ginkgo flavonoids can be 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts, 18 parts, 19 parts, 20 parts, 21 parts, 22 parts, 23 parts, 24 parts or 25 parts.

[0045] It should be noted that the weight proportion of saponin can be 25 to 50 parts. Based on the antioxidant, anti-inflammatory and neuroprotective effects of saponin, it can be combined with neuraminic acid to further reduce the deposition of Aβ protein and the damage of neurons caused by oxidative stress, thereby further improving the anti-neuroinflammation and anti-oxidative stress capabilities of the composite composition.

[0046] The weight proportions of the saponin can be 25 parts, 30 parts, 35 parts, 40 parts, 45 parts or 50 parts.

[0047] In some optional embodiments, the saponins include ginsenosides and notoginsenosides;

[0048] In these embodiments, ginsenosides are natural products that combine antioxidant, anti-inflammatory and neuroprotective effects. Existing studies have shown that ginsenosides have therapeutic effects on neuropsychiatric disorders, neurodegenerative diseases, memory and learning, etc.; in addition, notoginseng saponins have the effect of scavenging free radicals (existing studies have shown that notoginseng powder can protect brain tissue from ischemia-reperfusion injury by eliminating free radicals, inhibiting lipid peroxidation and stabilizing nerve cell membranes, and has a significant recovery effect on alleviating cerebral ischemia injury), protective effects on neuronal hypoxia (existing studies have shown that PNS in notoginseng can significantly delay the energy depletion of neurons that have been hypoxic for 2 hours, and promote the synthesis of high-energy phosphate compounds in cells during the reoxygenation period), and notoginseng saponins have the effect of directly protecting brain cells and improving local tissue blood circulation (existing studies have shown that this is the principle of notoginseng saponins' ability to resist cerebral ischemic injury and protect brain tissue). Therefore, the saponins can cooperate with neuraminic acid to further reduce the deposition of Aβ protein and the damage of oxidative stress to neurons, and further improve the ability of the composite composition to resist neuroinflammation and oxidative stress.

[0049] In some optional embodiments, the weight proportion of the ginsenoside is 20 to 30 parts, and the weight proportion of the notoginsenoside is 5 to 20 parts;

[0050] In these embodiments, the weight proportion of ginsenosides can be 20 to 30 parts, and the weight proportion of notoginseng saponins can be 5 to 20 parts. Through the anti-oxidative stress, anti-inflammatory and neuroprotective effects of ginsenosides, and the free radical scavenging effect, free radical scavenging protective effect and improvement of local tissue blood circulation of notoginseng saponins, saponins can be combined with neuraminic acid to further reduce the deposition of Aβ protein and the damage of neurons caused by oxidative stress, and further enhance the anti-neuroinflammation and anti-oxidative stress capabilities of the composite composition.

[0051] The weight proportions of the ginsenoside can be 20 parts, 21 parts, 22 parts, 23 parts, 24 parts, 25 parts, 26 parts, 27 parts, 28 parts, 29 parts or 30 parts.

[0052] The weight proportions of the notoginseng saponin can be 5 parts, 6 parts, 7 parts, 8 parts, 9 parts, 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts, 18 parts, 19 parts or 20 parts.

[0053] In some optional embodiments, the composite composition further comprises, by weight: 5 to 15 parts of solvent, 1 to 20 parts of co-emulsifier and 10 to 25 parts of emulsifier;

[0054] In these embodiments, the weight proportion of the solvent can be 5 to 15 parts, and the weight proportion of the emulsifier can be 10 to 25 parts. Through the interaction between the solvent and the emulsifier, astaxanthin, neuraminic acid and ginkgo flavonoids can be evenly dispersed, so that the composite composition has good protein homeostasis, anti-neuroinflammation and anti-oxidative stress capabilities; in addition, the weight proportion of the co-emulsifier can be 1 to 20 parts. Through the co-emulsifier, the solvent and the emulsifier can be further coordinated to evenly disperse astaxanthin, neuraminic acid and ginkgo flavonoids, so that the composite composition has good protein homeostasis, anti-neuroinflammation and anti-oxidative stress capabilities.

[0055] The weight parts of the solvent can be 5 parts, 6 parts, 7 parts, 8 parts, 9 parts, 10 parts, 11 parts, 12 parts, 13 parts, 14 parts or 15 parts.

[0056] The weight parts of the emulsifier can be 10 parts, 15 parts, 20 parts, 25 parts, 30 parts, 35 parts, 40 parts or 45 parts.

[0057] The weight proportion of the co-emulsifier can be 1 part, 2 parts, 3 parts, 4 parts, 5 parts, 10 parts, 15 parts or 20 parts.

[0058] In some optional embodiments, the solvent includes an oily base and / or water;

[0059] The auxiliary emulsifier includes: soybean lecithin and / or modified starch;

[0060] The emulsifier includes Span and / or Tween;

[0061] In these embodiments, the solvent may include an oily matrix and / or water, and the co-emulsifier may include soy lecithin and / or modified starch, and the emulsifier may include Span and / or Tween. Through the interaction between the solvent, the co-emulsifier and the emulsifier, astaxanthin, neuraminic acid and ginkgo flavonoids are evenly dispersed, so that the composite composition has good protein homeostasis, anti-neuroinflammation and anti-oxidative stress capabilities.

[0062] It should be noted that the use of the emulsifier and the co-emulsifier can quickly dissolve in the body and promote the rapid absorption of the composite composition by the body, so as to reduce the gastrointestinal burden of the body.

[0063] It should be noted that, in the case where the solvent includes an oily base and water, the weight proportion of the oily base may be 1 to 5 parts, and the weight proportion of water may be 5 to 10 parts.

[0064] It should be noted that, when the emulsifier includes Span and Tween, the weight proportion of Span can be 2 to 5 parts, and the weight proportion of Tween can be 10 to 20 parts.

[0065] It should be noted that the Span may be Span 60, and the Tween may be Tween 80.

[0066] It should be noted that, when the solvent includes water, the water may be oxygen-free water from which oxygen has been removed.

[0067] It should be noted that, in addition to soybean lecithin and modified starch, the co-emulsifier may also be modified soybean lecithin, etc. The co-emulsifier here can be randomly adjusted according to actual production requirements.

[0068] In some optional embodiments, when the solvent includes an oily base, the oily base includes at least one of the following: sunflower oil, soybean oil, safflower oil, walnut oil and maple seed oil;

[0069] In these embodiments, when the solvent includes an oily matrix, the oily matrix may include at least one of sunflower seed oil, soybean oil, safflower oil, walnut oil and Acer truncatum seed oil, and astaxanthin, neuraminic acid and ginkgo flavonoids are evenly dispersed through the oily matrix, so that the composite composition has good protein homeostasis, anti-neuroinflammation and anti-oxidative stress capabilities.

[0070] It should be noted that the Acer truncatum seed oil generally contains neuraminic acid. When the Acer truncatum seed oil is used in the oily matrix, it can also provide a sufficient amount of neuraminic acid components for the composite composition.

[0071] Figure 2 A schematic flow chart of a method for preparing a composite composition provided in an embodiment of the present application is shown exemplarily;

[0072] like Figure 2 As shown, based on a general inventive concept, an embodiment of the present application provides a method for preparing the composite composition, the method comprising:

[0073] S1. Under a first preset vacuum condition, the oily matrix, astaxanthin, nervonic acid and ginkgo flavonoids are first stirred and mixed to obtain a first mixed solution;

[0074] S2. The saponin and the solvent are stirred and mixed for a second time under a second preset vacuum condition to obtain a second mixed solution; and

[0075] S3. The first mixed liquid and the second mixed liquid are combined, and then an emulsifier and an emulsifier co-emulsifier are added to the combined mixed liquid under the first preset vacuum condition to perform the first stirring and mixing to obtain a composite composition.

[0076] This method is a method for preparing the above-mentioned composite composition. The specific composition of the composite composition can refer to the above-mentioned embodiment. Since this method adopts part or all of the technical solutions of the above-mentioned embodiment, it at least has all the beneficial effects brought by the technical solutions of the above-mentioned embodiment, which will not be described one by one here.

[0077] In some optional embodiments, the first stirring and mixing speed is 6500 rpm to 12000 rpm, the first stirring and mixing temperature is 50° C. to 65° C., and the first stirring and mixing time is 10 min to 20 min; and / or

[0078] The second stirring and mixing speed is ≥200 rpm, and the second stirring and mixing time is 10 min to 20 min; and / or

[0079] The first vacuum degree and the second vacuum degree are respectively -0.098MPa to -0.08MPa;

[0080] In these embodiments, the rotation speed of the first stirring and mixing can be 6500rpm~12000rpm, the temperature of the first stirring and mixing can be 50℃~65℃, and the time of the first stirring and mixing can be 10min~20min. The first stirring and mixing can promote the sufficient mixing of the oily matrix, astaxanthin, neuraminic acid and ginkgo flavonoids, or the combined mixed solution and the emulsifier and the co-emulsifier are fully mixed, so that a first mixed solution or a composite composition with uniform distribution of components can be obtained; in addition, the rotation speed of the second stirring and mixing can be ≥200rpm, and the time of the second stirring and mixing can be 10min~20min. Through the second stirring and mixing, the saponin and the solvent can be uniformly dispersed, so that a second mixed solution with uniform distribution of components can be obtained; in addition, the first vacuum degree and the second vacuum degree can be -0.098MPa~-0.08MPa, respectively, which can avoid the introduction of oxygen in the process of preparing the composite composition, thereby causing astaxanthin, neuraminic acid and ginkgo flavonoids to be oxidized prematurely, affecting the efficacy of astaxanthin, neuraminic acid and ginkgo flavonoids.

[0081] The rotation speed of the first stirring and mixing can be 6500rpm, 7000rpm, 7500rpm, 8000rpm, 8500rpm, 9000rpm, 9500rpm, 10000rpm, 10500rpm, 11000rpm, 11500rpm or 12000rpm.

[0082] The temperature of the first stirring and mixing can be 50°C, 51°C, 52°C, 53°C, 54°C, 55°C, 56°C, 57°C, 58°C, 59°C, 60°C, 61°C, 62°C, 63°C, 64°C or 65°C.

[0083] The first stirring and mixing time can be 10 min, 11 min, 12 min, 13 min, 14 min, 15 min, 16 min, 17 min, 18 min, 19 min or 20 min.

[0084] The second stirring and mixing time can be 10 min, 11 min, 12 min, 13 min, 14 min, 15 min, 16 min, 17 min, 18 min, 19 min or 20 min.

[0085] The first vacuum degree and the second vacuum degree may be -0.098 MPa, -0.096 MPa, -0.094 MPa, -0.092 MPa, -0.090 MPa, -0.088 MPa, -0.086 MPa, -0.084 MPa, -0.082 MPa or -0.080 MPa, respectively.

[0086] Based on a general inventive concept, an embodiment of the present application provides a capsule preparation for preventing and treating neurodegenerative diseases, wherein the capsule preparation comprises the composite composition described in the first aspect, and further comprises, by weight: 50 to 60 parts of gelatin, 20 to 30 parts of glycerol, 1 to 3 parts of caramel color and 50 to 60 parts of solvent.

[0087] The capsule preparation is realized based on the above-mentioned composite composition. The specific composition of the composite composition can refer to the above-mentioned embodiment. Since the capsule preparation adopts part or all of the technical solutions of the above-mentioned embodiment, it has at least all the beneficial effects brought by the technical solutions of the above-mentioned embodiment, which will not be described one by one here.

[0088] It should be noted that the weight proportion of gelatin can be 50 to 60 parts. The composite composition is wrapped with gelatin to form a capsule shell. In addition, the composite composition will be isolated during the condensation process of gelatin to prevent the composite composition from coming into contact with the air and being oxidized in advance, thereby maintaining the medicinal properties of the composite composition; the weight proportion of glycerin can be 20 to 30 parts. Glycerin can be used to promote the uniform dispersion of the composite composition into various components. At the same time, based on the viscosity, moisture retention and stability of glycerin, the composite composition can be prevented from coming into contact with the air and being oxidized, thereby maintaining the medicinal properties of the composite composition; the weight proportion of caramel color can be 1 to 3 parts. Caramel color can be used to improve the appearance of the capsule. Based on the antioxidant property of caramel color, the composite composition can be further prevented from coming into contact with the air and being oxidized, thereby maintaining the medicinal properties of the composite composition; the weight proportion of solvent can be 50 to 60 parts. Each component of the capsule preparation can be dispersed.

[0089] The weight proportions of the gelatin can be 50 parts, 51 parts, 52 parts, 53 parts, 54 parts, 55 parts, 56 parts, 57 parts, 58 parts, 59 parts or 60 parts.

[0090] The weight parts of the glycerol can be 20 parts, 21 parts, 22 parts, 23 parts, 24 parts, 25 parts, 26 parts, 27 parts, 28 parts, 29 parts or 30 parts.

[0091] The weight proportion of the caramel color can be 1 part, 2 parts or 3 parts.

[0092] The weight parts of the solvent can be 50 parts, 51 parts, 52 parts, 53 parts, 54 parts, 55 parts, 56 parts, 57 parts, 58 parts, 59 parts or 60 parts.

[0093] It should be noted that the solvent may be water.

[0094] Figure 3 A schematic flow chart of a method for preparing a capsule preparation provided in an embodiment of the present application is exemplarily shown;

[0095] like Figure 3 As shown, based on a general inventive concept, the present application embodiment provides a method for preparing a capsule preparation, the method comprising:

[0096] S1. heating and stirring the composite composition, the gelatin, the glycerin, the caramel color and the solvent to obtain a mixed glue solution;

[0097] S2. The mixed glue solution is vacuum degassed and insulated to obtain a glue product; and

[0098] S3. The colloid product is poured into capsule shells to prepare soft capsules, and then dried to obtain capsule preparations.

[0099] This method is a method for preparing the above-mentioned capsule preparation. The specific composition of the capsule preparation can refer to the above-mentioned embodiment. Since this method adopts part or all of the technical solutions of the above-mentioned embodiment, it at least has all the beneficial effects brought by the technical solutions of the above-mentioned embodiment, which will not be repeated here one by one.

[0100] It should be noted that the vacuum pressure of the vacuum degassing can be -0.098MPa to -0.08MPa; the rotation speed of the heating and stirring can be 30rpm to 50rpm, and the temperature of the heating and stirring and the insulation temperature can be 60°C to 70°C.

[0101] It should be noted that the vacuum degassing and heat preservation treatment operations can prevent the composite composition of the mixed glue from being oxidized, thereby maintaining the efficacy of the composite composition.

[0102] The present application is further described below in conjunction with specific examples. The experimental methods in the following examples where specific conditions are not specified are usually measured in accordance with national standards / industry standards; if there are no corresponding national standards / industry standards, they are measured in accordance with common international standards, conventional conditions or conditions recommended by the manufacturer.

[0103] Example 1

[0104] like Figure 1 As shown, a composite composition for preventing and treating neurodegenerative diseases comprises, by weight, 10 parts of astaxanthin, 5 parts of neuraminic acid, 25 parts of ginkgo flavonoids and 40 parts of saponin.

[0105] Saponins include ginsenosides and notoginsenosides.

[0106] In the case where the saponins include ginsenoside and notoginsenoside, the weight proportion of ginsenoside is 20 parts, and the weight proportion of notoginsenoside is 20 parts.

[0107] In parts by weight, the composite composition further comprises: 15 parts of solvent, 20 parts of auxiliary emulsifier and 13 parts of emulsifier.

[0108] Solvents include oily bases;

[0109] Co-emulsifiers include soy lecithin;

[0110] The emulsifier includes Span 60 and Tween 80, the weight portion of Span 60 is 1 part, and the weight portion of Tween 80 is 8 parts.

[0111] Where the solvent comprises an oily base, the oily base is sunflower oil.

[0112] like Figure 2 As shown, a method for preparing a composite composition comprises:

[0113] S1. Under a first preset vacuum condition, the oily matrix, astaxanthin, nervonic acid and ginkgo flavonoids are first stirred and mixed to obtain a first mixed solution;

[0114] S2. The saponin and the solvent are stirred and mixed for a second time under a second preset vacuum condition to obtain a second mixed solution; and

[0115] S3. The first mixed liquid and the second mixed liquid are combined, and then an emulsifier and an emulsifier are added to the combined mixed liquid under a first preset vacuum degree to perform a first stirring and mixing to obtain a composite composition.

[0116] The first stirring and mixing speed is 6500 rpm, the first stirring and mixing temperature is 50° C., and the first stirring and mixing time is 20 min;

[0117] The second stirring and mixing speed is 200 rpm, and the second stirring and mixing time is 20 min;

[0118] The first vacuum degree and the second vacuum degree are -0.098 MPa respectively.

[0119] A capsule preparation for preventing and treating neurodegenerative diseases, comprising a composite composition, and in parts by weight, the capsule preparation further comprises: 50 parts of gelatin, 20 parts of glycerol, 2 parts of caramel color and 60 parts of solvent.

[0120] like Figure 2 As shown, a method for preparing a capsule preparation comprises:

[0121] S1. The composite composition, gelatin, glycerin, caramel color and solvent were heated and stirred in a conventional rolling mode soft capsule machine to obtain a mixed gel;

[0122] S2. The mixed glue is vacuum degassed and insulated to obtain a glue product; and

[0123] S3. The colloid product is poured into capsule shells to prepare soft capsules, and then dried to obtain capsule preparations.

[0124] The vacuum pressure of the vacuum degassing was -0.098 MPa; the rotation speed of the heating and stirring was 50 rpm, and the temperature of the heating and stirring and the temperature of the insulation were 65°C.

[0125] Example 2

[0126] Based on the contents disclosed in Example 1, the following modifications are further made:

[0127] The composite composition comprises, by weight, 30 parts of astaxanthin, 15 parts of nervonic acid, 10 parts of ginkgo flavonoids and 35 parts of saponin.

[0128] In the case where the saponins include ginsenoside and notoginsenoside, the weight proportion of ginsenoside is 30 parts, and the weight proportion of notoginsenoside is 5 parts.

[0129] In parts by weight, the composite composition further comprises: 10 parts of solvent, 1 part of co-emulsifier and 12 parts of emulsifier.

[0130] The solvent includes oily base: 5 parts and water: 5 parts;

[0131] Co-emulsifiers include soy lecithin;

[0132] The emulsifier includes Span 60 and Tween 80, the weight portion of Span 60 is 2 parts, and the weight portion of Tween 80 is 10 parts.

[0133] The second stirring and mixing rotation speed is 2000 rpm.

[0134] An emulsified oral concentrate for preventing and treating neurodegenerative diseases, and a capsule preparation comprises a composite composition.

[0135] A method for preparing an emulsion oral concentrate, comprising:

[0136] S1. The composite composition is homogenized using a high-pressure high-speed homogenizer, and then the homogenized product is packaged under a vacuum environment to obtain an emulsion oral concentrate. The homogenization pressure is 200 MPa, the feed flow rate of the homogenization is 1 L / min to 100 L / min, the homogenization temperature is 50° C., and the homogenization time is 10 min.

[0137] Example 3

[0138] Based on the contents disclosed in Example 2, the following modifications are further made:

[0139] The composite composition comprises, by weight, 15 parts of astaxanthin, 15 parts of nervonic acid, 15 parts of ginkgo flavonoids and 45 parts of saponin.

[0140] Saponins include ginsenosides and notoginsenosides.

[0141] In the case where the saponins include ginsenoside and notoginsenoside, the weight proportion of ginsenoside is 25 parts, and the weight proportion of notoginsenoside is 20 parts.

[0142] In parts by weight, the composite composition further comprises: 12 parts of solvent, 20 parts of auxiliary emulsifier and 25 parts of emulsifier.

[0143] Solvents include oily bases;

[0144] Co-emulsifiers include soy lecithin;

[0145] The emulsifier includes Span 60 and Tween 80, the weight portion of Span 60 is 5 parts, and the weight portion of Tween 80 is 20 parts.

[0146] The rotation speed of the first stirring and mixing was 7000 rpm.

[0147] The second stirring and mixing rotation speed is 2000 rpm.

[0148] Comparative Example 1

[0149] Based on the contents disclosed in Example 1, the following modifications are further made:

[0150] The components of the composite composition do not include nervonic acid, ginkgo flavonoids and saponin, but only astaxanthin.

[0151] Comparative Example 2

[0152] Based on the contents disclosed in Example 1, the following modifications are further made:

[0153] The components of the composite composition do not contain ginkgo flavonoids and saponins, but only astaxanthin and nervonic acid.

[0154] Comparative Example 3

[0155] Based on the contents disclosed in Example 1, the following modifications are further made:

[0156] No saponin is added to the components of the composite composition, and only astaxanthin, nervonic acid and ginkgo flavonoids are added.

[0157] Comparative Example 4

[0158] Based on the contents disclosed in Example 1, the following modifications are further made:

[0159] The components of the composite composition do not contain notoginseng saponin, but only contain astaxanthin, nervonic acid, ginkgo flavonoids and ginsenosides.

[0160] Comparative Example 5

[0161] Based on the contents disclosed in Example 1, the following modifications are further made:

[0162] No ginsenoside is added to the components of the composite composition, and only astaxanthin, nervonic acid, ginkgo flavonoids and notoginsenoside are added.

[0163] Comparative Example 6

[0164] Based on the contents disclosed in Example 1, the following modifications are further made:

[0165] Astaxanthin is not added to the components of the composite composition, and only nervonic acid, ginkgo flavonoids, ginsenoside and notoginsenoside are added.

[0166] Comparative Example 7

[0167] Based on the contents disclosed in Example 1, the following modifications are further made:

[0168] The components of the composite composition do not contain ginkgo flavonoids, but only contain nervonic acid, astaxanthin, ginsenoside and notoginsenoside.

[0169] Comparative Example 8

[0170] Based on the contents disclosed in Example 1, the following modifications are further made:

[0171] The components of the composite composition do not contain nervonic acid, but only contain ginkgo flavonoids, astaxanthin, ginsenoside and notoginsenoside.

[0172] Related experiments and effect data:

[0173] Animal experiment process:

[0174] A plurality of experimental elderly rats (more than 96 rats, with no less than 8 rats in each group) were divided into 12 groups, wherein the blank group was not subjected to any treatment, while the experimental groups (Examples 1 to 3 and Comparative Examples 1 to 8) were fed with the corresponding composite compositions, and the feeding process was calculated according to the clinical dose of humans, and the equivalent dose was calculated for rats as the subjects. The results are shown in Table 1. The rats were gavaged according to the dosage recorded in Table 1, and the administration was continued for 14 days; wherein, the administration method was as follows: the composite composition was prepared into a solution with normal saline, and the control group and the model group were given an equal amount of normal saline. After the last administration, sodium pentobarbital was injected intraperitoneally for anesthesia, and the abdominal cavity of the rat was quickly opened after the righting reflex disappeared. Blood was collected through the abdominal aorta, left to stand for 30 minutes, and rotated at 3000 r·min at 4°C. -1 The rats were centrifuged at a speed of 15 minutes to separate the serum and stored at -20°C. The rats were then decapitated on ice, the skulls were opened and the rat brain tissues were completely removed. The blood in the rat brain tissues was rinsed with pre-cooled saline to quickly separate the hippocampal tissues, which were sealed in sterile cryopreservation tubes and stored at -80°C for later use. Before the test, the hippocampal tissues were minced and added to the RIPA lysis buffer. After centrifugation at 12000rpm for 30 minutes, the supernatant after centrifugation was taken and the content of striatal dopamine and 5-hydroxytryptamine, the content of various inflammatory factors, the content of malondialdehyde (MDA), the activity of superoxide dismutase (SOD), the activity of catalase (CAT) and the activity of glutathione peroxidase (GSH-Px) were detected by enzyme-linked immunosorbent assay. The results are shown in Table 2.

[0175] Table 1 Dosage of experimental animals in rats

[0176]

[0177] Table 2 Results of the efficacy test of the composite compositions of the embodiments and comparative examples

[0178]

[0179]

[0180] In Table 1, *P<0.05 vs blank group; **P<0.01 vs blank group; #P<0.05 vs comparative example 1 group; ##P<0.01 vs comparative example 1 group.

[0181] As shown in Table 1, a composite composition for preventing and treating neurodegenerative diseases provided by the embodiment of the present application can significantly improve the physiological function of the brain of experimental elderly rats, and can also effectively inhibit the secretion of inflammatory factors, and improve the content of striatal dopamine and 5-hydroxytryptamine in rats, while also reducing the malondialdehyde (MDA) content of cerebrospinal fluid and serum, and can also improve the activity of superoxide dismutase (SOD), composite catalase (CAT) and glutathione peroxidase (GSH-Px), which shows that the composite composition has significant protection of neurons, promotes neuronal regeneration, and also has the function of preventing neurodegenerative lesions. In addition, the various indicators of the experimental group in Table 1 are significantly better than those of the blank group, and the comprehensive efficacy of the composite composition of Example 1 for experimental elderly rats is stronger than that of the simple use of astaxanthin in comparative example 1 for experimental elderly rats, which shows that there is a good comprehensive synergistic effect between the various components of the composite composition, and also shows that the composite composition has good antioxidant activity, good astaxanthin protection, anti-neuroinflammatory ability, promotion of neuronal regeneration and cerebral vascular contraction and relaxation ability.

[0182] In addition, an embodiment of the present application provides a composite composition for preventing and treating neurodegenerative diseases. The composite composition can improve the anti-neuroinflammation and anti-oxidative stress capabilities of the composite composition through the synergistic effect between astaxanthin, neuraminic acid, ginkgo flavonoids and saponins, so that the composite composition has good protein homeostasis, anti-neuroinflammation and anti-oxidative stress capabilities.

[0183] In addition, the embodiments of the present application provide a composite composition for preventing and treating neurodegenerative diseases, which has the effect of delaying cerebrovascular aging, and the nutrition of the composite composition is more balanced, which is conducive to expanding the application market of astaxanthin foods and the development of related industries.

[0184] The above description is only a specific implementation of the present application, so that those skilled in the art can understand or implement the present application. It will be apparent to those skilled in the art that various modifications to these embodiments are possible, and the general principles defined in the present application can be implemented in other embodiments without departing from the spirit or scope of the present application. Therefore, the present application will not be limited to the embodiments shown in the present application, but will conform to the widest range consistent with the principles and novel features applied for by the present application.

Claims

1. A composite composition for preventing and treating neurodegenerative diseases, comprising, by weight: Astaxanthin: 10 to 30 parts, neuraminic acid: 5 to 15 parts, ginkgo flavonoids: 10 to 25 parts and saponins: 25 to 50 parts.

2. The composite composition according to claim 1, wherein the saponins include ginsenosides and notoginsenosides.

3. The composite composition according to claim 2, wherein the weight proportion of the ginsenoside is 20 to 30 parts, and the weight proportion of the notoginseng saponin is 5 to 20 parts.

4. The composite composition according to claim 1, further comprising, by weight: Solvent: 5 to 15 parts, co-emulsifier: 1 to 20 parts and emulsifier: 10 to 25 parts.

5. The composite composition according to claim 4, wherein the solvent comprises an oily matrix and / or water; The co-emulsifier includes: Soy lecithin and / or modified starch; The emulsifiers include Span and / or Tween.

6. The composite composition according to claim 4, wherein when the solvent comprises an oily base, the oily base comprises at least one of the following: sunflower seed oil, soybean oil, safflower oil, walnut oil and Acer truncatum seed oil.

7. A method for preparing the composite composition according to any one of claims 1 to 6, the method comprising: Under a first preset vacuum condition, the oily matrix, astaxanthin, nervonic acid and ginkgo flavonoids are first stirred and mixed to obtain a first mixed solution; Performing a second stirring mixing of the saponin and the solvent under a second preset vacuum degree to obtain a second mixed solution; as well as The first mixed liquid and the second mixed liquid are combined, and then an emulsifier and an auxiliary emulsifier are added to the combined mixed liquid under the condition of the first preset vacuum degree to perform the first stirring and mixing to obtain a composite composition.

8. The method according to claim 7, wherein the first stirring and mixing speed is 6500 rpm to 12000 rpm, the first stirring and mixing temperature is 50° C. to 65° C., and the second stirring and mixing time is 10 min to 20 min; and / or The second stirring and mixing speed is ≥200 rpm, and the first stirring and mixing time is 10 min to 20 min; and / or The first vacuum degree and the second vacuum degree are respectively -0.098 MPa to -0.08 MPa.

9. A capsule preparation for preventing and treating neurodegenerative diseases, the capsule preparation comprising the composite composition according to any one of claims 1 to 6, and further comprising, by weight: Gelatin: 50 parts to 60 parts, glycerin: 20 parts to 30 parts, caramel color: 1 part to 3 parts and solvent: 50 parts to 60 parts.

10. A method for preparing the capsule preparation according to claim 9, the method comprising: The composite composition, the gelatin, the glycerin, the caramel color and the solvent are heated and stirred to obtain a mixed glue solution; The mixed glue solution is subjected to vacuum degassing and heat preservation to obtain a glue solution product; as well as The colloid product is poured into capsule shells to prepare soft capsules, and then dried to obtain capsule preparations.

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