Compositions and uses thereof
By using compositions of oleanderol, chamomile and rosemary, oral administration to increase dopamine levels and provide neuroprotection, side effects in the prior art for the treatment of depression, anxiety, epilepsy and diabetic nephropathy are addressed. The obvious and limited therapeutic effect has achieved safer and more effective therapeutic effects.
Patent Information
- Application Number
- CN202411708791.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Priority Date
- 2020-07-14
- Filing Date
- 2021-07-13
- Publication Date
- 2025-02-11
AI Technical Summary
The prior art has problems of significant side effects and limited treatment effects when treating diseases such as depression, anxiety, epilepsy, and diabetic nephropathy.
A composition is provided, including oleanderol, chamomile and rosemary, administered by oral routes to increase dopamine levels, relieve symptoms and provide neuroprotection.
The composition has shown significant effects in increasing dopamine levels and providing antioxidant neuroprotection, which can effectively reduce symptoms associated with depression, anxiety, epilepsy and diabetic nephropathy and reduce the risk of disease.
Smart Images

Figure CN119405731A_ABST
Abstract
Description
This application is a divisional application of the patent application with application number 202180061153.5, application date July 13, 2021, and invention name “Compositions and Uses Thereof”. Technical Field
[0001] The present invention relates to a composition, particularly but not exclusively an oral composition, including a hydrosol, for improving the health of a subject. The present invention also relates to a method of treating and / or reducing the risk of a subject suffering from a disease. Background Art
[0002] People who work busy jobs or have busy schedules are usually under considerable stress in life. Prolonged stress and bad habits may lead to mental health problems, and may even lead to more serious mental illnesses, including depression, anxiety, eating disorders, social withdrawal, etc. Depression is one of the common mental illnesses, which can be very serious because it can significantly affect how people feel and act in a negative way. When people feel stressed, anxiety may also occur at the same time. In addition, mental illness may also lead to physical illness. For example, people with depression may be at risk for gastrointestinal disorders and cardiovascular diseases. The immune systems of people with mental illness are often fragile and susceptible to other health problems, including but not limited to diabetes, arthritis, autoimmune diseases, and even cancer.
[0003] Many drugs have been developed to treat different types of psychological or psychiatric disorders. For example, antidepressants such as fluoxetine, citalopram, paroxetine, sertraline, fluvoxamine are commonly used serotonin reuptake inhibitors to relieve symptoms associated with depression. However, these antidepressants may cause serious side effects such as nausea, headache, diarrhea, and decreased libido. Other existing drugs for treating depression include venlafaxine and duloxetine, which may cause increased blood pressure, headache, and constipation.
[0004] Epilepsy is a common neurological disorder today. According to epidemiological statistics, the annual incidence of epilepsy is about 50-70 / 100,000 people, and the prevalence is about 5‰. In addition, there are more than 6 million epilepsy patients in China, and 650,000 to 700,000 new epilepsy patients each year. This brain disease is characterized by the continued existence of persistent changes in the brain that can increase the likelihood of future epileptic seizures, and the corresponding consequences in terms of neurobiological, cognitive, psychological, and social dysfunction.
[0005] Current drugs for treating epilepsy cannot effectively prevent or cure epilepsy, but can only reduce or stop its attacks, and often require lifelong medication. However, most anti-epileptic drugs have adverse reactions, such as insensitivity, teratogenicity, and drug resistance in some patients, and the side effects are more obvious, with negative effects on patient behavior and cognitive function. This results in intermittent treatment and recurrence of the disease, making it difficult for patients to accept.
[0006] Diabetic nephropathy is the deterioration of the normal function of the kidneys caused by having diabetes. According to statistics, about 40% of people with diabetes will develop kidney disease. It has been found that diabetic nephropathy can be prevented or delayed by controlling blood sugar and blood pressure levels.
[0007] To help lower blood pressure, medications including angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are often used because they have been shown to protect kidney function and prevent further damage while lowering blood pressure. However, ACE inhibitors often produce side effects such as dry cough, hyperkalemia, and angioedema, while ARBs often cause dizziness, hyperkalemia, and headaches.
[0008] Therefore, there is a strong need to develop compositions and methods for promoting health, especially mental and spiritual health, without significant side effects or with minimal side effects, as well as methods for treating, preventing or reducing the risk of epilepsy, diabetic nephropathy, and physical diseases related to oxidative stress. Summary of the invention
[0009] According to one aspect of the present invention, a composition is provided, comprising orange blossom hydrosol, chamomile hydrosol and rosemary hydrosol.
[0010] According to another aspect of the present invention, a method for treating and / or reducing the risk of a subject suffering from a disease by administering an effective amount of the composition to the subject is provided.
[0011] According to another aspect of the present invention, there is provided a use of the composition in preparing a medicament for treating or reducing the risk of a disease.
[0012] Without wishing to be bound by theory, it is believed that the composition of the present invention may be effective for treating, preventing and / or reducing the risk of developing a disorder, particularly a neurodegenerative disease associated with oxidative stress, epilepsy, and diabetic nephropathy. The composition is also suitable for promoting psychological well-being in a subject; and / or increasing dopamine levels. Without wishing to be bound by theory, it is believed that the composition is capable of protecting neuronal cells under oxidative stress, e.g., minimizing undesirable effects triggered by oxidative stress. BRIEF DESCRIPTION OF THE DRAWINGS
[0013] Figure 1Two microscopic images of a normal zebrafish transfected with tyrosine hydroxylase-green fluorescent protein (TH-GFP) are shown, wherein the left image shows the expression of GFP in the zebrafish, and the right image was taken under a light microscope.
[0014] Figure 2 Two microscopic images of zebrafish transfected with TH-GFP and then incubated with the composition according to one embodiment of the present invention are shown, wherein the left image shows GFP expression in the zebrafish and the right image is taken under an optical microscope.
[0015] Figure 3 Two microscopic images of zebrafish transfected with TH-GFP and then incubated with the diluted composition are shown, wherein the left image shows GFP expression in the zebrafish and the right image was taken under a light microscope.
[0016] Figure 4 : is a bar graph showing the effect of a composition according to one embodiment of the present invention on neurites in SH-SY5Y cells after 24 hours of treatment.
[0017] Figure 5 is a bar graph showing the effect of a composition according to one embodiment of the present invention on neurites in SH-SY5Y cells after 48 hours of treatment.
[0018] Figure 6 is a bar graph showing the average length of neurites of SH-SY5Y cells treated with various concentrations of a composition according to an embodiment of the present invention before and after an oxidative stress challenge, wherein the cells were pretreated for 24 hours prior to the challenge.
[0019] Figure 7 is a bar graph showing the average length of SH-SY5Y cell neurites treated with various concentrations of a composition according to an embodiment of the present invention before and after oxidative stress challenge, wherein the cells were pretreated for 48 hours prior to the challenge.
[0020] Figure 8 Shown are changes in neurite length after 12 hours of treatment of cells, where the cells were subjected to an oxidative stress challenge prior to the addition of a composition according to one embodiment of the present invention.
[0021] Fig. 9 The cells were treated for 24 hours, i.e., the Figure 8 Results follow the changes in neurite length after an additional 12 hr. DETAILED DESCRIPTION
[0022] Unless otherwise specifically stated, all tests herein were conducted under standard conditions, including room and test temperatures of 25°C, sea level (1 atm.) pressure, pH 7, and all measurements were performed in metric units. In addition, unless otherwise specifically stated, all percentages, ratios, etc. herein are by weight. It should be understood that, unless otherwise specifically stated, the material compounds, chemicals, etc. described herein are generally commercial items and / or industry standard items available from various suppliers around the world.
[0023] As used herein, the term "hydrosol" refers to a liquid obtained by distillation, especially steam distillation of a part of a plant or the whole plant, followed by separation. It can be obtained by the same method of preparing essential oils from plant matter. Compared with the corresponding essential oil derived from the same plant matter, the hydrosol includes more water-soluble compounds, but fewer aromatic compounds. Therefore, it may be a transparent mixture containing suspended tiny droplets or particles, which are almost impossible to observe with the naked eye. Hydrosols may also be called hydrosols (hydrolat or hydrolate), distillates or flower waters. It should be understood that hydrosols can be obtained by distilling flowers, leaves, bark, stems, roots, berries, fruits, wood or other parts of plants, not necessarily just flowers.
[0024] As used herein, neroli hydrosol refers to a hydrosol derived from orange blossoms, and the orange blossoms may be from, but are not limited to, flowers of Citrus aurantium subsp. amara or Bigaradia.
[0025] As used herein, chamomile hydrosol refers to hydrosols derived from Matricaria chamomilla and / or Roman chamomile (Chamarmelum nobile).
[0026] As used herein, rosemary hydrosol refers to a hydrosol derived from rosemary (Rosmarinus officinalis).
[0027] As used herein, the term "oral pharmaceutical composition" refers to a composition suitable for therapeutic and / or prophylactic treatment or prevention of a disease by oral administration to a subject (i.e., by oral administration). Therefore, the oral pharmaceutical composition of the present invention can be in the form of a dispersion, emulsion, suspension, syrup, soft gelatin capsule, etc. In a preferred embodiment, the oral pharmaceutical composition is in the form of a dispersion, emulsion or suspension with or without a pharmaceutically acceptable excipient. Pharmaceutically acceptable excipients include liquid fillers, lubricants, diluents, solvents or encapsulating materials for carrying and delivering the active ingredients of the oral pharmaceutical composition to an organ or part of the body of the subject to exert a therapeutic effect.
[0028] The expression "effective amount" generally means an amount sufficient to produce the desired therapeutic result, wherein the exact nature of the result varies depending on the specific disorder being treated. When the disorder is accompanied by inflammation, the result is generally to inhibit or reduce the expression or functional activity of inflammatory factors. The result may also be to enhance the expression or functional activity of anti-inflammatory factors. When the disorder is associated with mental disorders such as depression and anxiety, the result may be to increase dopamine levels, increase well-being, improve sleep quality and / or increase appetite. When the disorder is associated with a neurodegenerative disorder, the result may be to increase neuronal cell growth or development, including the extension of neurite length and / or the delayed development of a nervous system disease. A physician or veterinarian with ordinary skills in the art will understand the effective amount of determining and prescribing a composition, particularly an effective amount of an oral pharmaceutical composition of the present invention. A physician or veterinarian will also be able to adjust the effective amount of the composition according to the severity of the condition to be alleviated.
[0029] In one embodiment herein, the present invention relates to a composition for promoting dopamine production, alleviating discomfort and / or alleviating symptoms associated with physical or mental illness. The composition herein is believed to be effective in increasing dopamine levels and having a neuroprotective effect against oxidative stress.
[0030] It is believed that by increasing the production of dopamine, the mental health of individual patients can be improved, as dopamine is a key reward neurotransmitter that regulates normal behavior, motivation, and emotion, and affects movement, memory, and attention. Generally, an increase in dopamine will lead to a better mood, and therefore is useful in regulating the subject's mood.
[0031] In one embodiment herein, the compositions of the present invention include one or more hydrosols derived from one or more plants.
[0032] Those skilled in the art know suitable methods for obtaining hydrosols from plant matter. Plant matter is non-genetically modified plant matter, and more preferably plant matter without pesticides and additives. One possible way to obtain hydrosols is by performing steam distillation. For example, steam is generated to pass through plant matter and cause the plant matter to release essential oils and other substances in the form of vapor. Then, the steam enters a condensation chamber surrounded by cold water to form a mixture, i.e., a condensate that returns from the gas phase to the liquid phase. The mixture is then subjected to a separator to separate at least two parts including an upper part and a lower part. The upper part refers to a layer floating on the mixture because it includes most of the volatile aromatic compounds extracted from the plant matter, which are usually lighter in weight, thereby forming concentrated essential oils. The lower part refers to a layer obtained at the bottom of the separator and below the floating layer. The lower part has a smaller amount of aromatic compounds than the upper part, and the compound is usually heavier than the compound in the upper part. The lower part is considered to be a water-based byproduct of the distillation process and is referred to as a hydrosol.
[0033] Hydrosols are considered to be less concentrated than essential oils and, depending on their application, can be applied to a subject without dilution. Compared to essential oils, they are generally safe to use and less irritating. Hydrosols can be of different grades and can be commercially available from suppliers or companies around the world. The hydrosols used to prepare the compositions of the present invention are therapeutic grade, i.e., have no detectable or only trace amounts of contaminants.
[0034] In one embodiment of the invention, the composition includes orange blossom hydrosol, chamomile hydrosol and rosemary hydrosol. It is believed that the combination of these hydrosols has an unexpected and expected effect in increasing dopamine levels and exerting a neuroprotective effect against oxidative damage. Therefore, it is useful in various applications, especially when it is administered to a single patient by the oral route. The composition in one embodiment of the present invention is formulated into an oral composition including oral pharmaceutical compositions, beverages, foods (including food supplements), etc.
[0035] Neroli hydrosol can have antibacterial and antifungal properties, as well as anti-inflammatory effects, especially when used on the skin.
[0036] Typically, chamomile hydrosol is used to promote calming effects on the skin, with moisturizing and soothing properties.
[0037] Rosemary has been used for flavoring foods and in aromatherapy for many years. Typically, rosemary hydrosol is applied topically for hair growth stimulation, skin rejuvenation, and pain relief.
[0038] The above-mentioned hydrosols are usually used for topical application to improve skin or hair conditions, or as indoor fragrances to relieve anxiety, and the inventors unexpectedly found that oral administration of the above-mentioned hydrosol combination can achieve excellent results in increasing dopamine levels, that is, promoting the psychological health of the subject and protecting neuronal cells from oxidative stress. Without wishing to be limited by theory, due to the increase in dopamine levels, it is also believed that the present invention can help alleviate symptoms associated with nervous system disorders (such as neurodegenerative disorders), metabolic disorders, autoimmune disorders, gastrointestinal disorders, cardiovascular diseases, psychological disorders or mental disorders.
[0039] In one embodiment, the volume ratio of orange blossom hydrosol to chamomile hydrosol to rosemary hydrosol is about 1:1:1 to about 10:1:1, such as about 1:1:1, about 2:1:1, about 3:1:1, about 4:1:1, about 5:1:1, about 6:1:1, about 7:1:1, about 8:1:1, about 9:1:1 or about 10:1:1. In a specific embodiment, the volume ratio of orange blossom hydrosol to chamomile hydrosol to rosemary hydrosol is about 6:1:1 to about 8:1:1, about 6:1:1 or about 8:1:1.
[0040] It should be understood that, depending on its use, the composition may include one or more additional hydrosols, additives, carriers and / or therapeutic agents. In one embodiment in which the composition further includes additional hydrosols, the volume ratio of orange blossom hydrosol to chamomile hydrosol to rosemary hydrosol to additional hydrosols may be about 5:1:1:3, about 6:1:1:2 or about 7:1:1:1.
[0041] In addition to the hydrosol, the composition can include about 0% to about 99.9% water by volume based on the total volume of the composition, ranging from about 0.5% to about 99.5%, about 5% to about 95%, about 10% to about 90%, about 20% to about 80%, about 30% to about 70%, about 40% to about 60%, about 50%, about 60%, about 70%, about 80% or about 90%. The volume of water refers to the water added to the hydrosol, which does not include the original water content in the hydrosol. In one embodiment, the volume ratio of the total hydrosol to water can be about 1:1 to about 1:20, about 1:1, about 1:2, about 1:5, about 1:9, about 1:10, about 1:15, about 1:19 or about 1:20. In another embodiment, the volume ratio of the total hydrosol to water can be about 0.5:99.5 to about 5:95, specifically about 0.5:99.5, about 1:99 or about 2:98.
[0042] It is believed that the composition of the present invention may be effective in inducing dopamine production. By conducting experiments on transgenic zebrafish as described in the examples, it was observed that dopamine levels increased. There are also clinical observations that the composition can help improve well-being and relieve stress and anxiety. Without being limited by theory, it is therefore believed that the composition is suitable for preparing beverages, and oral compositions for promoting health, including psychological and mental health of the user. It is also believed that the composition herein may have an antioxidant effect.
[0043] In one embodiment in which the volume ratio of total hydrosol to water is about 1:99 or about 0.5:99.5, the composition can be provided as a beverage for daily drinking. Users may find the composition containing water easier to drink, especially after exercise or in warm or hot weather. At the same time, the presence of water can help improve blood circulation and promote the absorption of hydrosol.
[0044] The water for preparing the composition can be purified drinking water, which can be selected from the group consisting of distilled water, deionized water, mineral water, reverse osmosis water (abbreviated as "RO water"), and combinations thereof. In one embodiment, water is RO water. RO water refers to water purified by using a partially permeable membrane under applied pressure. RO water is generally free of minerals including heavy metals, and has a reduced suspended chemical and biological contaminant content. Therefore, it is clean and safe to drink, and is suitable for preparing oral preparations. In an embodiment in which the composition can be provided as a beverage, the composition includes at least about 10% by volume to about 90% by volume of the RO water based on the total volume of the composition. In another embodiment, the composition includes about 50% by volume to about 95% by volume or about 75% by volume to about 99% by volume of the RO water based on the total volume of the composition.
[0045] In one embodiment herein, the composition of the present invention includes about 0.1% to about 10% by volume of orange blossom hydrosol, about 0.01% to about 1% by volume of chamomile hydrosol, and about 0.01% to about 1% by volume of rosemary hydrosol, based on the total volume of the composition. The composition may also include at least about 50% by volume of water, or about 75.0% to about 99.9% by volume of water, based on the total volume of the composition.
[0046] In a specific embodiment, the composition includes about 0.4% by volume of orange blossom hydrosol, about 0.05% by volume of chamomile hydrosol, about 0.05% by volume of rosemary hydrosol and about 99.5% by volume of water. In an alternative embodiment, the composition includes about 0.3% by volume of orange blossom hydrosol, about 0.1% by volume of additional hydrosol, about 0.05% by volume of chamomile hydrosol, about 0.05% by volume of rosemary hydrosol and about 99.5% by volume of water. It should be understood that these embodiments including a higher proportion of water are suitable for being formulated into beverages required for daily use. Continuous intake of the composition helps to enhance the individual's immune system and improve his / her mood. The composition can also help relieve stress. Children or adults can drink more than 100 ml per day (e.g., 350 ml per day), and the composition can be provided as a packaged beverage. The composition can also be provided to the patient as part of treatment, depending on the amount and frequency of application of the composition.
[0047] In another embodiment herein, the composition of the present invention includes at least about 40% by volume of orange blossom hydrosol, at least about 5% by volume of chamomile hydrosol and at least about 5% by volume of rosemary hydrosol based on the total volume of the composition. In particular, the composition includes about 50% by volume to about 80% by volume of orange blossom hydrosol, about 5% by volume to about 20% by volume of chamomile hydrosol and about 5% by volume to about 20% by volume of rosemary hydrosol, and optionally, water. For example, the composition includes about 80% by volume of orange blossom hydrosol, about 10% by volume of chamomile hydrosol and about 10% by volume of rosemary hydrosol based on the total volume of the composition. These compositions include a higher proportion of total hydrosols and are suitable for formulation into pharmaceutical compositions or for administration as part of therapeutic therapy.
[0048] The composition of the present invention (especially its hydrosol) generally comprises volatile aromatic compounds, which include at least α-terpineol, linalool, 1,8-cineole, camphor and coumarin. In one embodiment, α-terpineol, linalool, 1,8-cineole, camphor and coumarin are found in orange blossom hydrosol, chamomile hydrosol, and rosemary hydrosol. In one embodiment, the composition comprises at least about 50 mg / L of α-terpineol, at least about 20 mg / L of linalool, at least about 5 mg / L of 1,8-cineole, at least about 1 mg / L of camphor, and at least about 1 mg / L of coumarin.
[0049] In one embodiment, the composition may include about 50 mg / L to about 120 mg / L, about 70 mg / L to about 110 mg / L, or about 80 mg / L to about 100 mg / L of alpha-terpineol; about 20 mg / L to about 100 mg / L, about 40 mg / L to about 80 mg / L, or about 50 mg / L to about 70 mg / L of linalool; about 5 mg / L to about 45 mg / L, about 15 mg / L to about 35 mg / L, or about 20 mg / L to about 30 mg / L of 1,8-cineole; about 1 mg / L to about 30 mg / L, about 10 mg / L to about 20 mg / L, or about 15 mg / L to about 18 mg / L of camphor; and • From about 1 mg / L to about 15 mg / L, from about 1 mg / L to about 7 mg / L, or from about 2 mg / L to about 5 mg / L of coumarin.
[0050] In one embodiment, particularly when the composition is provided as a beverage, the composition includes about 80 mg / L to about 90 mg / L of alpha-terpineol, about 50 mg / L to about 60 mg / L of linalool, about 25 mg / L to about 30 mg / L of 1,8-cineole, about 15 mg / L to about 18 mg / L of camphor and about 2 mg / L to about 3 mg / L of coumarin. Without being limited by theory, it is believed that the above-mentioned components including alpha-terpineol, linalool, 1,8-cineole, camphor and coumarin in the composition actively promote the health of the subject. It should be understood that the composition may further include, for example, linoleic acid, oleic acid, linalool oxide (furan type), methyl anthranilate, borneol, citronellol, palmitic acid, geraniol, and the like. The amount of the above-mentioned components in the composition can be determined by a suitable method in the art. For example, the components can be determined by gas chromatography (GC) based on standard protocols and standard references in research or commercial laboratories.
[0051] In addition, the pH of the composition is about 4.0 to about 8.0, about 5.0 to about 7.0, or about 6.0 to about 6.5, and the pH value is suitable for the subject to drink.
[0052] As mentioned above, the composition can be formulated as a pharmaceutical composition, especially an oral pharmaceutical composition. For ease of storage and administration, the composition can further include a relatively small amount of preservatives.
[0053] The subject herein is typically a mammal, such as a rodent, a carnivore or a human. In one embodiment, the subject is a human.
[0054] In another embodiment, the composition can be formulated into eye drops and / or eye washes to rinse the user's eyes or relieve eye discomfort. For example, a composition formulated into an eye drop solution can include about 99.5% by volume of pure water, such as distilled water or reverse osmosis water, based on the total volume of the composition, and about 0.5% by volume of total hydrosol. The total hydrosol includes the above-mentioned orange blossom hydrosol, chamomile hydrosol and rosemary hydrosol, and in particular, the volume ratio is about 8:1:1. In other words, the composition herein is also suitable for administration via the ocular route. It is believed that the composition of the present invention can help alleviate eye irritation and pain caused by dust, undesirable irritating gas particles, pollutants and / or chemicals that come into contact with the eyes. It is also believed that the composition in the form of an oral composition can help alleviate the discomfort caused by the above-mentioned substances in the same situation, including pain and irritation and inflammation in the respiratory tract.
[0055] In another embodiment, the composition can be provided as a beverage to provide nutrition and water to the subject. The beverage can be provided in a bottle, a can or any suitable container as a packaged beverage. The beverage can be a nourishing and refreshing beverage, while gently promoting the health of the subject. For example, after drinking the beverage, dopamine levels may increase, so the subject may feel happier and relaxed. It can help users relieve stress and improve sleep quality. In addition, due to the presence of tiny droplets / particles suspended in the beverage (such as droplets of essential oils or aromatic compounds present in the composition), the shaking of the beverage will emit a receivable, sweet and fruity aroma, and the user may find it more refreshing and soothing. It should be understood that the above-mentioned composition can also be added to food.
[0056] Therefore, the compositions are suitable for preparing oral pharmaceutical compositions, eye drops, eye wash solutions, foods including food supplements, and beverages for promoting the health of a subject, respectively.
[0057] In another aspect, the present invention relates to a method for treating, preventing and / or reducing the risk of a subject suffering from a disease. The disease may be selected from the group consisting of: a nervous system disease (e.g., a neurodegenerative disease), a metabolic disease, an autoimmune disease, a gastrointestinal disease, a cardiovascular disease, a psychological disease, and a psychiatric disease. The method comprises the step of administering an effective amount of the above composition to the subject. The subject is also as described above, particularly a rodent, a carnivore, or a human.
[0058] In one embodiment where the subject is a human, the composition is prepared as a pharmaceutical composition and administered to the subject in a volume of about 1 ml to about 30 ml per day, or about 3 ml to about 10 ml per day, depending on the severity of the condition to be alleviated. In one embodiment, the composition is formulated in the form of an oral pharmaceutical composition and can therefore be administered by an oral route.
[0059] The methods of the present invention effectively treat, prevent and / or reduce the risk of suffering from conditions associated with pain, muscle abnormalities, headaches, dyspnea, depression, anxiety, fatigue, difficulty sleeping and / or dysphagia. It should be understood that, depending on the condition of the subject, the composition can be administered to the subject in combination with one or more additional therapeutic agents (e.g., including the pharmaceutical composition described in Hong Kong Short-term Patent No. HK1221598 published on June 2, 2017, with inventor Lai Dongqing).
[0060] The present invention further relates to a method of alleviating symptoms associated with the above-mentioned disorders by administering to a subject an effective amount of the composition of the present invention. It should be understood that the present invention also relates to the use of the composition of the present invention in the preparation of a medicament for treating or preventing the above-mentioned disorders.
[0061] The examples listed below further illustrate the present invention. Those skilled in the art will appreciate that the above embodiments and the examples given below are not intended to be limiting. Example 1 Preparation of composition
[0062] In the following examples, the compositions of the present invention were prepared from the following ingredients: 3482.5 ml of reverse osmosis (R0) water; 14 ml of orange blossom hydrosol (therapeutic grade); 1.75 ml of chamomile hydrosol (therapeutic grade); and 1.75 ml of rosemary hydrosol (therapeutic grade). The total amount of the composition is 3500 ml and can be filled into ten bottles, each bottle comprising 350 ml of the composition. The pH is 6. All hydrosols used to prepare the composition are therapeutic grade and can be obtained through commercial suppliers.
[0063] GC test was conducted to confirm the major components in the composition prepared according to the present invention. GC test was conducted by the laboratory according to standard test conditions and procedures. Table 1 shows the 10 components in the composition in addition to other components.
[0064] Table 1. GC results of the 10 components in the composition.
[0065] In order to determine if the composition is safe for the user to drink or administer with the therapeutic agent, several tests were performed to evaluate the heavy metal content and microbial content.
[0066] Samples of the composition were analyzed to determine the content of heavy metals. Heavy metal testing was performed by a laboratory according to standard testing conditions and procedures. Prior to determining total metals, the samples were digested by a method developed based on the United States Environmental Protection Agency (USEPA) method 3005. The results are as follows.
[0067] Table 2. Results of heavy metal testing of samples of the compositions.
[0068] According to the results, the heavy metal content in the composition did not exceed the drinking water guideline value recommended by the World Health Organization (WH0), please refer to the Guidelines for Drinking Water Quality issued by WHO.
[0069] Next, another sample of the composition was subjected to microbiological testing. Microbiological testing was also performed by the laboratory according to standard testing conditions and procedures. In this test, coliform bacteria including Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and heterotrophic organisms were not present in the composition. They were not detected in the test.
[0070] Based on the test results, the composition does not have excessive heavy metal and microbial contaminants and is therefore safe to drink and can be provided to consumers and individuals as beverages including drinking water. Example 2 Effects on dopamine production
[0071] Dopamine is a key reward neurotransmitter that plays an important role in the brain's reward system. It regulates normal behavior, motivation, and mood, and affects movement, memory, and concentration. Generally, an increase in dopamine will lead to a better mood, and is therefore useful in regulating a subject's mood.
[0072] Tyrosine hydroxylase (TH) is the rate-limiting enzyme in dopamine synthesis. The expression of TH can reflect the level of dopamine in a subject. Therefore, a test was performed to determine the effect of the composition of the present invention in dopamine production by using transfected zebrafish. In particular, green fluorescent protein (GFP) was used to transfect zebrafish to indicate the presence of TH.
[0073] like Figure 2 As shown, Figure 1 Compared to the control group shown, TH-GFP expression was enhanced after the transfected zebrafish was treated with the composition of the present invention (ie, the composition prepared in Example 1). Another transfected zebrafish was treated with the diluted composition (ie, the composition was diluted 1 / 10). Figure 3 The results shown indicate that the diluted composition has less effect on TH-GFP expression than the undiluted composition. The effect of the composition may be dose-dependent.
[0074] Based on the results, the composition of the present invention can induce TH levels, thereby increasing the production of dopamine. Subjects administered or treated with the composition can have a better mood and show improved motor or emotional responses. Example 3 Neuroprotective effect
[0075] In order to investigate whether the composition of the present invention has any protective effect on neurons under oxidative stress, a neurite outgrowth assay was performed.
[0076] It is assumed that the protective effect of the composition can be reflected by changes in neurite length. When the average length of neurites increases or remains substantially unchanged after an oxidative challenge, the composition is considered to have a protective effect on neurites, such as protecting neurites from oxidative stress. In other words, when the average length of neurites decreases after an oxidative challenge, the composition cannot exert a protective effect.
[0077] In the experiment, SH-SY5Y cells, a human neuroblastoma cell line ( CRL-2266 TM ). Before subjecting cells to oxidative stress, experiments were performed to evaluate the effects of the composition of the present invention on cells, such as determining a suitable working concentration range for cells. Compositions of different concentrations were prepared by diluting the composition with a common cell culture medium (DMEM / F12). First, SH-SY5Y cells were treated with a composition (composition of Example 1) at a concentration of 1%, 0.1%, 0.01% or 0.001% for 24 or 48 hours, according to the following groups.
[0078] Table 3. Concentrations of the compositions in the control group and the four treatment groups.
[0079] At the specified time point, the treated cells were fixed and incubated in PBS for subsequent measurements. The length of neurites in SH-SY5Y cells was measured by MoticImage Plus 2.0 software. Thirty cells were counted in each group. The average length (AU) of neurites was plotted relative to the control group and the treatment group for comparison. The statistical significance of multiple experimental data was determined by the Student's paired t-test of two groups of samples, and the results were expressed as mean ± standard deviation. In the test, p < 0.05 was considered statistically significant.
[0080] Figure 4 The average length of neurites after 24 hours of treatment of cells with the composition is shown. Similar to the control group, there was no significant change in the length of neurites in groups B, C and D (i.e., treated with 0.1%, 0.01% or 0.001% of the composition). However, group A was significantly reduced, indicating that 1% of the composition may not be suitable for SH-SY5Y cells. Similarly, Figure 5 The average length of neurites after treating cells with the composition for 48 hours is shown. The results show that the incubation time does not significantly change the effect of the composition on the cells. Groups B, C and D have no significant effect on the cells, while group A causes a decrease in neurite length. Therefore, it is believed that for SH-SY5Y cells, the composition can work better at concentrations of 0.1%, 0.01% and 0.001%.
[0081] In the next experiment, SH-SY5Y cells were pretreated with different concentrations of the composition and then challenged with hydrogen peroxide-induced oxidative stress. The treated cells were then incubated in a humidified incubator at 37°C and 5% CO2 for 24 and 48 hours. After incubation, the cells were challenged with 500mM hydrogen peroxide (H2O2) at 37°C for 3 hours to induce oxidative stress. At the specified time point, the treated cells were fixed and incubated in PBS for measurement. The length of neurites in SH-SY5Y cells was measured by Motic Image Plus 2.0 software. Thirty cells were counted in each group. The average length (AU) of neurites was plotted relative to the control group and the treatment group for comparison. The statistical significance of multiple experimental data was determined by the Student's paired t-test of two groups of samples, and the results were expressed as mean ± standard deviation. In the test, p < 0.05 was considered statistically significant, where p ≤ 0.05 *, p ≤ 0.01 **, p ≤ 0.001 ***.
[0082] Figure 6 Shown are the average lengths of neurites of SH-SY5Y cells in different groups before and after oxidative stress challenge, where cells were pretreated for 24 hours before the challenge.
[0083] Each group has two results (i.e., "Before" and "After"), which indicate the results obtained for each group before and after the H2O2 challenge. After the challenge, the average length of neurites in the control group was significantly reduced by more than 50%, which means that the cells were in a state of obvious stress. For the cells in groups B, C, and D, there was no significant change in the average length of neurites after incubation with the composition before the challenge. Although the average length of neurites decreased or remained almost unchanged after the challenge, its length was still higher than that of the control group. Therefore, compared with the control group, the composition was found to have a protective effect on neurons at volume concentrations of 0.1%, 0.01%, and 0.001%.
[0084] For the cells in Group A, the results indicated that the 1% composition was not suitable for incubating SH-SY5Y cells because it could induce significant oxidative stress in the cells. Therefore, a lower concentration of the composition was preferred.
[0085] Figure 7 Shown are the average lengths of neurites of SH-SY5Y cells in different groups before and after oxidative stress challenge, where cells were pretreated for 48 hours before the challenge.
[0086] Similar to the 24-hour pretreatment, the length of the neurites in the control group after the challenge after the 48-hour pretreatment was significantly reduced. For the cells in the B and C groups (i.e., cells treated with 0.1% and 0.01% of the composition before the challenge) had a longer average length than the control group (p value <0.001). Even at a concentration of 0.001%, the average length of the neurites was still moderately longer than the average length of the control group (p value <0.05). Therefore, it was found that the composition had a protective effect on neurons at a relatively low concentration.
[0087] The results of group A cells indicated that the 1% composition was not suitable for incubating SH-SY5Y cells because it could induce significant oxidative stress in the cells.
[0088] Based on the above results, it was found that if the cells were pretreated with the composition of the present invention, the cell damage caused by H2O2 challenge was alleviated. Therefore, the results suggest that the composition can alleviate the oxidative damage of SH-SY5Y cells challenged with H2O2. Example 4 Therapeutic effects on neurons
[0089] Another neurite outgrowth assay was performed to determine whether the composition can stimulate the recovery and growth of nerve cells that have been damaged by oxidants. Similar to Example 3, neurite length was used to determine the neuroprotective effect under oxidative stress. SH-SY5Y cells were used in the assay and exposed to H2O2 for 5 hours before adding and incubating the composition of the present invention.
[0090] Interestingly, it was found that the length of neurites decreased after 12 hours and then grew again within another 12 hours, although the length of the neurites was still not comparable to their initial length.
[0091] First, SH-SY5Y cells were divided into 4 groups, namely a control group and three treatment groups, after exposure to H2O2. The composition of different concentrations was prepared as follows, and the control group refers to a cell sample not treated with the composition.
[0092] Table 4. Concentrations of compositions in the control group and the three treatment groups.
[0093] After addition of the composition, the cells were incubated for 24 hours, and the length of neurites was measured at 12 and 24 hours.
[0094] Figure 8The changes in neurite length after 12 hours of treatment are shown. The results show that the composition can alleviate the effects caused by H2O2 challenge, in particular, cells treated with the composition have increased neurite length. Likewise, the lower the concentration of the composition, the better the neuroprotective effect of extending neurites against oxidative stress.
[0095] Fig. 9 The changes in neurite length after 24 hours of treatment are shown. Although the neurite length of the control group after an additional 12 hours of incubation almost returned to its initial length, the treated group still exhibited a significantly increased length compared to the control group. Therefore, the composition has a neuroprotective effect on cells under oxidative stress. Example 5 Therapeutic effects on epilepsy
[0096] In order to investigate whether the composition of the present invention (ie, the composition of Example 1) has any inhibitory effect on epilepsy (EP), various experiments were conducted on mice experimentally affected by epilepsy.
[0097] As known to those skilled in the art, pentylenetetrazol (PTZ) is a very strong epileptogen, and its epilepsy model is considered to be one of the ideal systemic tonic convulsion models. PTZ itself has no special neurotoxic effects, so it is widely used in the study of the pathogenesis of epilepsy and the screening of anti-epileptic drugs. When PTZ induces epilepsy in mice, the characteristics of its epileptic seizures are that clonic seizures are the main initial stage, and then there will be systemic tonic convulsions soon. PTZ is a central nervous system stimulant that acts on the GABA-GABAA receptor system. It promotes the enhancement of the facilitation process of excitatory synapses and reduces the release of GABA. This in turn reduces the inhibitory function, increases the sensitivity of convulsions, and increases the excitability of the central nervous system, thereby inducing EP. According to its seizure characteristics, in this experiment, these two forms of seizures are used as indicators and combined with the current Racine standard to analyze its epileptic behavior.
[0098] Carbamazepine (CBZ) was also used as a comparison group in this study. CBZ is a known anticonvulsant that works by reducing the nerve impulses that cause epileptic seizures and neuralgia. It has a stabilizing effect and can reduce the sensitivity of nerve cell membranes to Na + and Ca 2+ It can also increase the permeability of GABA, thereby reducing the excitability of cells. It prolongs the refractory period and may also enhance the synaptic transmission function of GABA.
[0099] First, 72 healthy male ICR mice were randomly divided into 6 groups, each with 12 mice, namely, a blank control group (0.5 volume % sodium carboxymethyl cellulose solution), a PTZ model group (0.5 volume % sodium carboxymethyl cellulose solution), a carbamazepine group (80 mg / kg carbamazepine), and high, medium and low dose groups of the composition of the present invention. Each group of test mice was gavaged daily for 7 consecutive days. 30 minutes after the last administration, except for the blank control group, the remaining groups of mice were intraperitoneally injected with 80 mg / kg PTZ to induce convulsive seizures in mice. Each mouse was placed in a cage and observed for 30 minutes, and behavioral changes such as epileptic seizure grade, duration, latency and mortality of the mice were recorded.
[0100] The Racine grading standard (see: https: / / en.wikipedia.org / wiki / Racine_stages) was used to determine the grade of epilepsy in mice: Level 0: No reaction; Grade I: wet dog shakes, facial muscle twitching, clonus, tremors (such as blinking, whisker twitching, rhythmic chewing, etc.); Grade II: Grade I seizure plus rhythmic nodding; Grade III: Grade II seizure plus forelimb clonus, but no hindlimb rearing; Grade IV: There is hindlimb rearing and bilateral falls with tilt, or hindlimb rearing with forelimb clonus; and Grade V: loss of balance, toppling, limb twitching, generalized clonus, generalized tonic-clonic, falling, rolling and loss of positional control.
[0101] First, an experiment was conducted to determine the effect of the composition of the present invention on the seizure behavior of PTZ-induced epileptic mice. After intraperitoneal injection of PTZ in mice, the mice showed EP symptoms. As can be seen from Table 5, compared with the model group, the composition of the present invention has a significant improvement effect on the behavior of epileptic mice. In this experiment, there were statistical differences (p<0.05) between the high, medium and low dose groups of the composition, among which #p<0.05 compared with the blank group; *p<0.05 compared with the model group.
[0102] Table 5. Effects on seizure behavior in PTZ-induced epileptic mice (n=12).
[0103] Then, experiments were conducted to determine the effect of the composition on PTZ-induced epileptic mice. Studies have shown that PTZ can induce convulsions by reducing the content of GABA in mouse brain tissue, so intraperitoneal injection of 80 mg / kg PTZ in mice can induce the possibility of convulsions. Table 6 shows the effect of the composition on convulsions in PTZ-induced epileptic mice, where compared with the blank group, #p<0.05; compared with the model group, *p<0.05; **p<0.01. Compared with the blank control group, all mice in the PTZ model group had convulsions, indicating that the model was successful. Compared with the PTZ model group, the high-dose group can significantly prolong the convulsion latency of PTZ-induced epileptic mice, shorten the duration of convulsions, reduce the intensity of convulsions, and reduce the mortality rate.
[0104] Table 6. Effects on convulsions in PTZ-induced epileptic mice (n=12).
[0105] In addition, experiments were conducted to determine the effect of the composition on the number of seizures in PTZ-induced epileptic mice. Table 7 shows the results of the experiment, where compared with the blank group, #p<0.05; compared with the model group, *p<0.05; **p<0.01. Compared with the model group, the carbamazepine group and the high-dose group can significantly reduce the number of seizures in grade IV EP mice (p<0.05). The high-dose group can significantly reduce the number of seizures in grade IV and V EP mice (p<0.01). The medium-dose group can significantly reduce the number of seizures in grade V EP mice (p<0.01). The low-dose group can significantly reduce the number of seizures in grade V EP mice (p<0.05).
[0106] Table 7. Effects on the number of seizures in PTZ-induced epileptic mice (n=12).
[0107] After the behavioral observation was completed by the above-mentioned related indicators, an experiment was conducted to study the effect of the composition on the content of NO, Na-K-ATP, Asp, and 5-HT in the brain of convulsive mice. After the behavioral observation, the mice were immediately killed, and the brain tissue and required organs were quickly removed and weighed, and then the brain tissue was placed in liquid nitrogen and stored in a -80°C refrigerator. The surface blood was washed off with pre-cooled saline before measurement. The tissue was then weighed, and PBS was added at a volume ratio of 1:9 to fully homogenize the brain tissue, and the homogenate was centrifuged at 3000r / min for 20 minutes. The supernatant was collected as a sample for subsequent ELISA tests for GABA, Glu, NO, Na + -K + The contents of ATP, Asp, 5-HT, etc. were tested.
[0108] As shown in Table 8, compared with the blank control group, the N0 concentration in the brain tissue of mice in the PTZ model group was significantly increased (p<0.01). Compared with the PTZ model group, both the high-dose and medium-dose groups could significantly (p<0.05) reduce the N0 concentration in the brain of convulsive mice, but the effect was slightly worse than that of carbamazepine, and the low-dose group had no significant effect (p>0.05).
[0109] Table 8. Effects on the contents of NO, Na-K-ATP, Asp, and 5-HT in the brain of convulsive mice (n=12).
[0110] Based on the above experimental results, it was found that the composition of the present invention can effectively resist PTZ-induced epileptic seizures in mice, reduce their excitability, reduce epileptic seizures and their severity, and has a significant and good anti-epileptic effect with a dose-dependent effect.
[0111] It is well known that the content of GABA, Glu, Asp and 5-HT in the brain is crucial to the occurrence of epilepsy. Glu and Asp are excitatory amino acids, while GABA and 5-HT are inhibitory amino acids. Excessive Glu content can destroy neurotoxins of central neurons, thereby generating excitement and causing brain damage.
[0112] In this example, both high and medium doses of the composition can significantly regulate the GABA concentration in the brain tissue of PTZ-induced epileptic mice, thereby reducing the degree of brain tissue damage. GABA receptors are divided into two types, GABAa and GABAb, and GABA receptors are expressed on Glu synaptic terminals and GABA synaptic terminals. GABAb receptor agonists can activate these receptors and inhibit GABAergic and Glu synapses, thereby inhibiting the release of GABA and Glu, and exerting a central inhibitory effect. Experiments have shown that both high and medium doses of the composition can significantly alleviate the increase in Glu concentration in the brain tissue of mice caused by N-methyl-D-aspartate (NMDA), increase 5-HT levels, reduce Asp levels, and effectively reduce the level of epilepsy, prolong the latency of convulsions, shorten the time of epileptic seizures, and have a good anti-epileptic effect. Example 6 Therapeutic effect on diabetic gastropathy
[0113] In order to investigate whether the composition of the present invention has any inhibitory effect on diabetic nephropathy (DN), various experiments were conducted on experimental rats.
[0114] First, under normal feeding and drinking conditions, each rat was first intraperitoneally injected with 0.5 mL of complete Fu's adjuvant (CFA), and then intraperitoneally injected with streptozotocin (STZ) solution (dose 30 mg / kg) the next day. The above steps were repeated once a week for 2 consecutive weeks. 72 hours after the second injection of STZ, diabetic (DM) rats with fasting blood glucose values between 16.8-25 mmol / L were selected and continued to be raised for a total of 30 days. The preliminary test results showed that on the 30th day of the experiment, compared with the normal group rats, the microalbuminuria (MALB) in the urine of DM rats increased significantly, and the kidney weight / body weight ratio and glomerular filtration rate (GFR) increased, indicating that DM rats had kidney lesions, proving that the DN model was successful. The model group and transgenic (GM) group shown in Table 9 used the above DN model. The GM group rats were gavaged at 8 o'clock in the morning on the day of grouping (i.e., the composition of the present invention), and the normal control group and the model control group were given physiological saline, with a capacity of 1 mL / 100 g body weight, once a day, for 4 consecutive weeks.
[0115] In order to measure serum angiotensin II (Ang II), the rats were fasted for 12 hours after the last administration. After anesthesia, 6 mL of blood was collected from the femoral vein and placed in ethylenediaminetetraacetic acid (EDTA) and heparin anticoagulation tubes. The plasma was separated by centrifugation at 3000 r / min at 4°C and stored at low temperature for testing.
[0116] As shown in Table 9 (compared with the normal group, *p<0.01; compared with the model group, #p<0.01), compared with the normal control group, Ang II in the model group increased. After GM treatment, Ang II decreased, which was significantly different from the model group (p<0.01).
[0117] Table 9. Effects of Ang II on DN rats.
[0118] In addition, experiments were also conducted to determine the effect of the composition of the present invention on the kidney weight / body weight ratio and GFR. One hour after the last administration, the bilateral kidneys were removed and weighed with an electronic balance to calculate the kidney weight / body weight ratio. In addition, one hour after the last administration, the rats were anesthetized with sodium pentobarbital, blood was collected from the abdominal aorta, and serum was separated by centrifugation. The day before the rats were killed, urine from each group of rats within 24 hours was collected by the metabolic cage method. The colorimetric method was used to determine the blood and urine creatinine content. Based on the blood and urine creatinine values and the urine volume per minute, GFR was calculated, where GFR = urine creatinine × urine volume per minute / blood creatinine.
[0119] As shown in Table 10 (compared with the normal group, *p<0.01; compared with the model group, #p<0.01), compared with the normal control group, the kidney weight / body weight ratio and GFR of the model group rats increased. After GM treatment, the kidney weight / body weight ratio and GFR decreased, which were significantly different from the model group (p<0.01).
[0120] Table 10. Effects on kidney weight / body weight ratio and glomerular filtration rate in DN rats.
[0121] Non-limiting embodiments of the present invention include:
[0122] 1. A composition comprising orange blossom hydrosol, chamomile hydrosol and rosemary hydrosol.
[0123] 2. According to the composition of embodiment 1, the volume ratio of the orange blossom hydrosol to the chamomile hydrosol and the rosemary hydrosol is 1:1:1 to 10:1:1.
[0124] 3. A composition according to embodiment 1, wherein the composition comprises about 0.1% to about 10% by volume of the orange blossom hydrosol, about 0.01% to about 1% by volume of the chamomile hydrosol, and about 0.01% to about 1% by volume of the rosemary hydrosol, based on the total volume of the composition.
[0125] 4. The composition according to embodiment 1 further comprises at least 50% by volume of water based on the total volume of the composition.
[0126] 5. The composition according to embodiment 1 further comprises about 75.0 volume % to about 99.9 volume % of water based on the total volume of the composition.
[0127] 6. The composition according to any one of embodiments 1 to 5, wherein the composition comprises: - about 50 mg / L to about 120 mg / L of alpha-terpineol; - from about 20 mg / L to about 100 mg / L linalool; - from about 5 mg / L to about 45 mg / L 1,8-cineole; - from about 1 mg / L to about 30 mg / L of camphor; and - From about 1 mg / L to about 15 mg / L of coumarin.
[0128] 7. The composition according to embodiment 6, wherein the composition comprises: - about 70 mg / L to about 110 mg / L of alpha-terpineol, - from about 40 mg / L to about 80 mg / L of linalool, - about 15 mg / L to about 35 mg / L of 1,8-cineole, - from about 10 mg / L to about 20 mg / L of camphor, and - From about 1 mg / L to about 7 mg / L of coumarin.
[0129] 8. The composition according to embodiment 6, wherein the composition comprises: - about 80 mg / L to about 100 mg / L of alpha-terpineol, - from about 50 mg / L to about 70 mg / L of linalool, - about 20 mg / L to about 30 mg / L of 1,8-cineole, - from about 15 mg / L to about 18 mg / L of camphor, and - From about 2 mg / L to about 5 mg / L of coumarin.
[0130] 9. The composition according to embodiment 6, wherein the composition comprises: - about 80 mg / L to about 90 mg / L of alpha-terpineol, - from about 50 mg / L to about 60 mg / L of linalool, - about 25 mg / L to about 30 mg / L of 1,8-cineole, - from about 15 mg / L to about 18 mg / L of camphor, and - From about 2 mg / L to about 3 mg / L of coumarin.
[0131] 10. The composition of any one of embodiments 1 to 5, wherein the pH is from about 5 to about 7.
[0132] 11. The composition according to any one of embodiments 1 to 5, wherein the composition is an oral composition.
[0133] 12. The composition according to embodiment 11, wherein the composition is a pharmaceutical composition or a beverage composition.
[0134] 13. A method of treating and / or reducing the risk of a subject suffering from a disease by administering to the subject an effective amount of the composition according to any one of embodiments 1 to 12.
[0135] 14. The method of embodiment 13, wherein the disease is selected from the group consisting of: a nervous system disease, a metabolic disease, an autoimmune disease, a gastrointestinal disease, a cardiovascular disease, a psychological disease, and a psychiatric disease; or a neurodegenerative disease.
[0136] 15. The method of embodiment 13, wherein the disorder is associated with a condition selected from the group consisting of pain, muscle abnormalities, headache, dyspnea, depression, anxiety, fatigue, difficulty sleeping and / or dysphagia.
[0137] 16. The method of embodiment 13, wherein the composition is administered to the subject in combination with one or more additional therapeutic agents.
[0138] 17. A method according to embodiment 13, wherein the disease is a neurodegenerative disease associated with oxidative stress.
[0139] 18. The method of embodiment 14, wherein the neurological disorder is epilepsy.
[0140] 19. The method of embodiment 14, wherein the metabolic disorder is diabetic nephropathy.
[0141] 20. The method of embodiment 13, wherein the disorder reduces dopamine production.
[0142] 21. Use of the composition according to any one of embodiments 1 to 12 in the preparation of a medicament for treating or reducing the risk of a disease.
[0143] 22. The use according to embodiment 21, wherein the disease is selected from the group consisting of: a nervous system disease, a metabolic disease, an autoimmune disease, a gastrointestinal disease, a cardiovascular disease, a psychological disease and a psychiatric disease; or a neurodegenerative disease.
[0144] 23. The use according to embodiment 21, wherein the medicament comprises one or more additional therapeutic agents.
[0145] 24. The use according to embodiment 21, wherein the disorder is associated with a condition selected from the group consisting of pain, muscle abnormalities, headache, dyspnea, depression, anxiety, fatigue, difficulty sleeping and / or dysphagia.
[0146] 25. The use according to embodiment 21, wherein the disease is a neurodegenerative disease associated with oxidative stress.
[0147] 26. The use according to embodiment 21, wherein the composition promotes dopamine production.
[0148] 27. The use according to embodiment 22, wherein the neurological disorder is epilepsy.
[0149] 28. The use according to embodiment 22, wherein the metabolic disorder is diabetic nephropathy.
[0150] It will be appreciated by those skilled in the art that many changes and / or modifications may be made to the present invention without departing from the scope of the invention as broadly described, as shown in the specific embodiments. Therefore, the present embodiments are to be considered in all aspects as illustrative and not restrictive.
[0151] All references specifically cited herein are hereby incorporated by reference in their entirety. However, unless otherwise stated, any reference to prior art contained herein is not an admission that the information is common general knowledge.
Claims
1. A composition, characterized in that The active ingredients of the composition are composed of orange blossom hydrosol, chamomile hydrosol and rosemary hydrosol, and the composition includes 0.1 volume % to 10 volume % of the orange blossom hydrosol, 0.01 volume % to 1 volume % of the chamomile hydrosol, 0.01 volume % to 1 volume % of the rosemary hydrosol, and at least 50 volume % of water based on the total volume of the composition, wherein: The composition is used for treating and / or reducing the risk of a subject suffering from a disorder selected from the group consisting of epilepsy and a neurodegenerative disorder associated with oxidative stress; or the composition is used for promoting dopamine production.
2. The composition according to claim 1, characterized in that The composition includes 75.0 volume % to 99.9 volume % water based on the total volume of the composition.
3. The composition according to claim 1 or 2, characterized in that The composition comprises: -50mg / L to 120mg / L alpha-terpineol; -20mg / L to 100mg / L linalool; -5 mg / L to 45 mg / L 1,8-cineole; -1mg / L to 30mg / L of camphor; and -1mg / L to 15mg / L of coumarin.
4. The composition according to claim 3, characterized in that The composition comprises: 70 mg / L to 110 mg / L of α-terpineol; 40 mg / L to 80 mg / L of linalool; 15 mg / L to 35 mg / L of 1,8-cineole; 10 mg / L to 20 mg / L of camphor; and 1 mg / L to 7 mg / L of coumarin.
5. The composition according to claim 4, characterized in that The composition comprises: 80 mg / L to 100 mg / L of alpha-terpineol; 50 mg / L to 70 mg / L of linalool; 20 mg / L to 30 mg / L of 1,8-cineole; 15 mg / L to 18 mg / L of camphor; and 2 mg / L to 5 mg / L of coumarin.
6. The composition according to claim 5, characterized in that The composition comprises: 80 mg / L to 90 mg / L of α-terpineol; 50 mg / L to 60 mg / L of linalool; 25 mg / L to 30 mg / L of 1,8-cineole; 15 mg / L to 18 mg / L of camphor; and 2 mg / L to 3 mg / L of coumarin.
7. The composition according to claim 1, characterized in that The pH of the composition is 5 to 7.
8. The composition according to claim 1, characterized in that The composition includes an oral composition, a pharmaceutical composition, or a combination of the two.
9. The composition according to claim 8, characterized in that The oral composition is in liquid form.
10. Use of the composition according to any one of claims 1 to 9 in the preparation of a medicament for treating or reducing the risk of a disorder selected from the group consisting of epilepsy and a neurodegenerative disorder associated with oxidative stress; or, the composition is used to promote dopamine production.