NAD < + >-containing composition and application thereof

Abstract

The invention relates to an NAD < + >-containing composition and application thereof, and relates to the technical field of medicines, the NAD < + >-containing composition comprises the following components in parts by weight: 1-5 parts of NAD < + >, 16-22 parts of clinacanthus nutans extract and 5-10 parts of rabdosia serra extract. The NAD +, the clinacanthus nutans extract and the rabdosia lophanthoides extract in a proper proportion are matched for use, and it is found that the composition can remarkably adjust the thyroid hormone level and the related antibody content in a model rat experiment, and the nodule condition of thyroid tissue is effectively relieved. The discovery not only reveals the potential value of the composition in the aspect of treating the nodular thyroid disease, but also opens up a new direction for clinical application of NAD +, clinacanthus nutans and rabdosia serra, and has wide practical application value.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a composition containing NAD+ and uses thereof. Background Art

[0002] Nodular thyroid disease, as a major intractable disease of the endocrine system, poses a serious threat to the patient's quality of life and health. The core symptom of the disease is thyroid nodules, which are often accompanied by disorders in thyroid hormone levels and abnormal increases in related antibodies. Its pathogenesis is complex, covering the intertwined influence of multiple factors such as genetics, environment, and immunity. Although a variety of treatment methods such as drug therapy, surgical intervention, and radiotherapy have been explored in clinical practice, each has certain limitations, such as large fluctuations in efficacy, significant side effects, or high recurrence rates. Therefore, exploring new, safe, and efficient treatment methods has become an urgent need for research in this field.

[0003] NAD+ (nicotinamide adenine dinucleotide), as an indispensable coenzyme in organisms, is deeply involved in a series of key physiological activities such as cellular energy metabolism, DNA repair, and cell signal transduction. In recent years, with the continuous deepening of research on NAD+, its important role in energy regulation, anti-oxidative stress, anti-inflammatory response, neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, metabolic diseases such as diabetes and obesity, and anti-aging has gradually been revealed. These discoveries not only expand our understanding of the biological functions of NAD+, but also open up broad prospects for its application in clinical treatment and health care.

[0004] Alligator mouth flower, scientifically known as Clinacanthus nutans (Burm.f.) Lindau, is a herbaceous plant of the genus Clinacanthus in the family Acanthaceae. According to the "Guangxi Plant List", in traditional medicine, alligator mouth flower has multiple functions such as regulating menstruation, removing blood stasis, reducing swelling and relieving pain, and is widely used to treat diseases such as fractures, anemia, jaundice, and rheumatism. Modern scientific research has further confirmed that alligator mouth flower is rich in active ingredients such as flavonoid carbon glycosides, lupeol, and glycoproteins, which show significant effects in anti-cancer. At the same time, alligator mouth flower also has a wide range of pharmacological effects such as anti-oxidation, enhancing immunity, antibacterial and anti-inflammatory, and its potential effects in anti-cancer, lowering blood pressure, lowering blood lipids, and softening blood vessels have also attracted much attention.

[0005] Rabdosia lophanthoides is a perennial herb belonging to the genus Rabdosia of the family Lamiaceae. Both its roots and the whole plant can be used as medicine, which has the effects of clearing away heat and detoxifying, promoting dampness and relieving jaundice, cooling blood and dispersing blood stasis. It plays an important role in the treatment of diseases such as acute icteric hepatitis, acute cholecystitis, and contusion and blood stasis.

[0006] It is worth noting that although NAD+, alligator beak flower and narrow-lined sedge each show great potential in the fields of medicine and health care, there are no reports in the existing technology on the combined use of these three for the treatment of nodular thyroid disease. Summary of the invention

[0007] In order to solve the above problems, the present invention provides a composition containing NAD+ and use thereof.

[0008] In a first aspect, the present invention provides a composition containing NAD+, wherein the composition containing NAD+ comprises the following components in parts by weight:

[0009] 1-5 parts of NAD+, 16-22 parts of alligator mouth flower extract and 5-10 parts of narrow-lined schisandra extract.

[0010] Further, the NAD+-containing composition comprises the following components in parts by weight:

[0011] 3 parts of NAD+, 20 parts of alligator mouth flower extract and 8 parts of narrow-lined schisandra extract.

[0012] Furthermore, the alligator mouth flower extract includes alligator mouth flower petroleum ether extract.

[0013] Furthermore, the preparation method of the petroleum ether extract of Crocodile Mouth Flower comprises the following process:

[0014] The crushed crocodile mouth flower and petroleum ether are mixed in a weight ratio of 1: (5-10), and then soaked at room temperature for 5-10 days to obtain a mixture;

[0015] The mixture is filtered and the obtained filter residue is continuously rinsed with petroleum ether for 1 to 3 times, and then the filtrate and the rinsing liquid are concentrated and dried under reduced pressure to obtain the petroleum ether extract of alligator flower.

[0016] Furthermore, the extract of the Herba Lycoris radiatae comprises a water extract of the Herba Lycoris radiatae.

[0017] Furthermore, the preparation method of the water extract of the narrow-lined striated schizonepeta includes the following steps:

[0018] The crushed whole herb of the narrow-lined sedge and water are mixed in a weight ratio of 1: (5-10), and then reflux extraction is performed to obtain an extract;

[0019] The extract is concentrated under reduced pressure and dried to obtain the water extract of the Ipomoea acuta.

[0020] Furthermore, the working condition parameters of the reflux extraction include: temperature of 100-110° C., time of 60-90 minutes, and number of times of 1-3 times.

[0021] In a second aspect, the present invention provides the use of the NAD+-containing composition described in any one of the first aspects in the preparation of a drug for treating nodular goiter.

[0022] Furthermore, the drug for treating nodular goiter includes an effective ingredient and a pharmaceutically acceptable excipient, wherein the effective ingredient is the NAD+-containing composition described in any one of the first aspects, and the pharmaceutically acceptable excipient includes at least one of a filler, a disintegrant, a lubricant, a binder and a sweetener.

[0023] Furthermore, the dosage form of the drug for treating nodular goiter includes at least one of injection, powder, tablet, capsule, granule and pill.

[0024] The above technical solution provided by the embodiment of the present invention has at least the following advantages compared with the prior art:

[0025] The embodiments of the present invention provide a composition containing NAD+ and its use. The present invention uses a suitable proportion of NAD+, alligator flower extract and narrow-lined schizonepeta extract in combination, and it is found that the composition can significantly regulate thyroid hormone levels and related antibody content in model rat experiments, and effectively alleviate the nodular condition of thyroid tissue. This discovery not only reveals the potential value of the composition in the treatment of nodular thyroid disease, but also opens up a new direction for the clinical application of NAD+, alligator flower and narrow-lined schizonepeta, and has a wide range of practical application value. DETAILED DESCRIPTION

[0026] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution of the present invention will be clearly and completely described in combination with the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0027] Unless otherwise specified, various raw materials, reagents, instruments and equipment used in the present invention can be purchased from the market or prepared by existing methods.

[0028] In a first aspect, the present invention provides a composition containing NAD+, wherein the composition containing NAD+ comprises the following components in parts by weight:

[0029] 1-5 parts of NAD+, 16-22 parts of alligator mouth flower extract and 5-10 parts of narrow-lined schisandra extract.

[0030] The embodiment of the present invention provides a composition containing NAD+. The present invention uses a suitable proportion of NAD+, alligator flower extract and narrow-lined schizonepeta extract in combination. It is found that the composition can significantly regulate thyroid hormone levels and related antibody content in model rat experiments, and effectively alleviate the nodular condition of thyroid tissue. This discovery not only reveals the potential value of the composition in the treatment of nodular thyroid disease, but also opens up a new direction for the clinical application of NAD+, alligator flower and narrow-lined schizonepeta, and has a wide range of practical application value.

[0031] In some specific embodiments, preferably, the NAD+-containing composition comprises the following components in parts by weight:

[0032] 3 parts of NAD+, 20 parts of alligator mouth flower extract and 8 parts of narrow-lined schisandra extract.

[0033] In some specific embodiments, preferably, the alligator mouth flower extract includes alligator mouth flower petroleum ether extract.

[0034] In some specific embodiments, the preparation method of the petroleum ether extract of Crocodile Mouth Flower comprises the following process:

[0035] The crushed crocodile mouth flower and petroleum ether are mixed in a weight ratio of 1: (5-10), and then soaked at room temperature for 5-10 days to obtain a mixture;

[0036] The mixture is filtered and the obtained filter residue is continuously rinsed with petroleum ether for 1 to 3 times, and then the filtrate and the rinsing liquid are concentrated and dried under reduced pressure to obtain the petroleum ether extract of alligator flower.

[0037] In some specific embodiments, preferably, the extract of Ipomoea acuta includes an aqueous extract of Ipomoea acuta.

[0038] In some specific embodiments, the method for preparing the water extract of Ipomoea australis comprises the following process:

[0039] The crushed whole herb of the narrow-lined sedge and water are mixed in a weight ratio of 1: (5-10), and then reflux extraction is performed to obtain an extract;

[0040] The extract is concentrated under reduced pressure and dried to obtain the water extract of the Ipomoea acuta.

[0041] In some specific embodiments, the working condition parameters of the reflux extraction include: temperature of 100-110° C., time of 60-90 minutes, and number of times of 1-3 times.

[0042] In a second aspect, based on the same inventive concept, the present invention provides the use of the NAD+-containing composition described in any one of the first aspects in the preparation of a drug for treating nodular goiter.

[0043] In some specific embodiments, the drug for treating nodular goiter includes an effective ingredient and a pharmaceutically acceptable excipient, wherein the effective ingredient is the NAD+-containing composition described in any one of the first aspects, and the pharmaceutically acceptable excipient includes at least one of a filler, a disintegrant, a lubricant, a binder and a sweetener.

[0044] In the present invention, "pharmacologically acceptable" may also be referred to as "pharmaceutical", which means a substance that is not biologically or otherwise substantially undesirable, that is, the substance can be administered to an individual without causing any undesirable biological effects or interacting in a harmful manner with any other component of the composition containing the substance. Specifically: These excipients include but are not limited to:

[0045] 1. Fillers: such as lactose, sucrose, starch, etc., are used to increase the volume of the drug to facilitate preparation molding and dosage control.

[0046] 2. Disintegrants: such as cross-linked sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, etc., can promote the rapid disintegration and dissolution of drugs in the body, which is beneficial to the rapid release and absorption of drugs.

[0047] 3. Lubricants: such as magnesium stearate, talc, etc., are used to reduce friction between drug particles, improve the fluidity of the preparation, and facilitate production and packaging.

[0048] 4. Binders: such as hydroxypropyl methylcellulose, povidone K30, etc., can enhance the binding force between drug particles and ensure the integrity and stability of the preparation.

[0049] 5. Sweeteners: such as aspartame, sucralose, etc., are used to improve the taste of the drug and increase the patient's compliance with the drug, which is especially important for patients who need to take the drug for a long time.

[0050] In some specific embodiments, the dosage form of the drug for treating nodular goiter includes at least one of injection, powder, tablet, capsule, granule and pill.

[0051] In the present invention, the dosage form of the drug for treating nodular goiter can be prepared according to actual production needs and existing dosage form preparation processes. For example:

[0052] 1. Injection

[0053] Preparation process:

[0054] Raw material preparation: First, accurately weigh the NAD+-containing composition and necessary auxiliary materials (such as stabilizers, pH adjusters, osmotic pressure regulators, etc.).

[0055] Dissolving and mixing: Dissolve the NAD+-containing composition in an appropriate amount of solvent, such as water for injection, and add other excipients, and mix them thoroughly and evenly by stirring or ultrasonic treatment.

[0056] Filtration and filling: Filter the mixed solution through a microporous membrane to remove impurities and particles, then fill it into sterile glass or plastic bottles and seal them.

[0057] Sterilization and inspection: The filled injection solution is sterilized by high-pressure steam or filtration, and then quality inspected to ensure sterility, pyrogen-free, and free of foreign matter.

[0058] 2. Powder

[0059] Preparation process:

[0060] Raw material crushing: Crush the NAD+-containing composition and auxiliary materials (such as fillers, glidants, etc.) into appropriate particle sizes respectively.

[0061] Mixing: Mix the crushed raw materials evenly according to the formula ratio, which can be achieved by mechanical stirring or manual stirring.

[0062] Repackaging: Repack the mixed powder into sealed packages, such as aluminum foil bags or plastic bottles, and label them.

[0063] 3. Tablets

[0064] Preparation process:

[0065] Raw material processing: The NAD+-containing composition and excipients (such as fillers, disintegrants, lubricants, etc.) are pre-treated, such as crushing, screening, etc.

[0066] Mixing and granulation: Mix the processed raw materials evenly, add appropriate amount of water or binder to make wet granules, and then dry them to obtain dry granules.

[0067] Tableting: The dry granules are compressed into tablets by a tablet press, and lubricants may be added to reduce friction as needed.

[0068] Coating: Tablets can be coated as needed to improve stability or taste.

[0069] 4. Capsules

[0070] Preparation process:

[0071] Raw material preparation and mixing: Similar to tablets, mix the NAD+-containing composition and excipients evenly.

[0072] Filling: Fill the mixed raw materials into empty capsules, which can be done manually or by automatic filling machine.

[0073] Sealing and Packaging: The filled capsules are sealed and then packed into sealed packages.

[0074] 5. Granules

[0075] Preparation process:

[0076] Raw material handling and mixing: Similar to powders, crush the raw materials and mix them evenly.

[0077] Granulation: The mixed raw materials are made into granules by wet granulation or dry granulation process.

[0078] Drying and granulation: The prepared wet granules are dried and then passed through a granulator to obtain uniform granules.

[0079] Packaging: Put the granules into sealed packages and label them.

[0080] 6. Pills

[0081] Preparation process:

[0082] Raw material preparation and mixing: Mix the NAD+-containing composition and auxiliary materials evenly, and add an appropriate amount of adhesive or lubricant if necessary.

[0083] Pill making: Pills are made by hand or by a pill making machine. The size and shape of the pills can be adjusted as needed.

[0084] Drying and Packaging: The prepared pellets are dried to remove excess moisture and then packed into airtight packages.

[0085] It should be noted that, unless otherwise specified or described, the components and raw materials involved in the NAD+-containing composition and its use provided in the embodiments of the present invention can be directly commercially available products or homemade according to existing preparation processes. At the same time, the operation steps involved in the NAD+-containing composition and its use provided in the embodiments of the present invention can be carried out in a conventional manner in the art or using existing equipment unless otherwise specified or described, and will not be described one by one here.

[0086] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are intended only to illustrate the present invention and are not intended to limit the scope of the present invention. The experimental methods in the following examples that do not specify specific conditions are usually measured according to national standards. If there is no corresponding national standard, then the conditions recommended by the manufacturer are followed.

[0087] Example 1

[0088] This example provides a composition containing NAD+, which includes the following components in parts by weight:

[0089] 3 parts of NAD+, 20 parts of alligator mouth flower extract and 8 parts of spathiphyllum striolatum extract;

[0090] The crocodile mouth flower extract is a crocodile mouth flower petroleum ether extract, and the preparation method thereof comprises the following steps: mixing crushed crocodile mouth flower and petroleum ether in a weight ratio of 1:8, and then soaking them at room temperature for 7 days to obtain a mixture; filtering the mixture and further eluting the obtained filter residue with petroleum ether for 3 times, and then concentrating and drying the filtrate and the eluting liquid under reduced pressure to obtain the crocodile mouth flower petroleum ether extract;

[0091] The extract of the narrow-lined Camellia oleracea is a narrow-lined Camellia oleracea water extract, and its preparation method comprises the following process: the crushed narrow-lined Camellia oleracea whole plant and water are mixed in a weight ratio of 1:8, and then reflux extraction is performed at a temperature of 105° C. for 60 minutes, the extraction is performed twice, and the extracts are combined; the extract is concentrated under reduced pressure and dried to obtain the narrow-lined Camellia oleracea water extract.

[0092] Example 2

[0093] This example provides a composition containing NAD+, which includes the following components in parts by weight:

[0094] 1 part of NAD+, 16 parts of alligator mouth flower extract and 5 parts of spathiphyllum striolatum extract;

[0095] The preparation method of the alligator mouth flower extract is the same as that in Example 1;

[0096] The preparation method of the extract of Ipomoea australis is the same as that of Example 1.

[0097] Example 3

[0098] This example provides a composition containing NAD+, which includes the following components in parts by weight:

[0099] 5 parts of NAD+, 22 parts of alligator mouth flower extract and 10 parts of spathiphyllum striolatum extract;

[0100] The preparation method of the alligator mouth flower extract is the same as that in Example 1;

[0101] The preparation method of the extract of Ipomoea australis is the same as that of Example 1.

[0102] Comparative Example 1

[0103] This example provides a composition containing NAD+, which is different from Example 1 only in that the amount of alligator flower extract used is 0 parts (i.e., no alligator flower extract is added); the remaining steps and parameters are the same.

[0104] The above-mentioned NAD+-containing composition comprises the following components in parts by weight:

[0105] 3 parts of NAD+ and 8 parts of Ipomoea australis extract;

[0106] The preparation method of the extract of Ipomoea australis is the same as that of Example 1.

[0107] Comparative Example 2

[0108] This example provides a composition containing NAD+, which is different from Example 1 only in that: the extract of Stylophora serrata is 0 parts (that is, the extract of Stylophora serrata is not added); the other steps and parameters are the same.

[0109] The above-mentioned NAD+-containing composition comprises the following components in parts by weight:

[0110] 3 parts of NAD+ and 20 parts of alligator flower extract;

[0111] The preparation method of the alligator flower extract is the same as that in Example 1.

[0112] Comparative Example 3

[0113] This example provides a composition containing NAD+, which is different from Example 1 only in that the amount of alligator mouth flower extract is 8 parts and the amount of scutellaria baicalensis extract is 20 parts; the other steps and parameters are the same.

[0114] The above-mentioned NAD+-containing composition comprises the following components in parts by weight:

[0115] 3 parts of NAD+, 8 parts of alligator mouth flower extract and 20 parts of spatholobifolia extract;

[0116] The preparation method of the alligator mouth flower extract is the same as that in Example 1;

[0117] The preparation method of the extract of Ipomoea australis is the same as that of Example 1.

[0118] Test Case

[0119] In this example, according to the experimental method disclosed in the prior art, a rat model of nodular goiter was established by intragastric administration of propylthiouracil, and the pharmacological effects of the NAD+-containing compositions provided in Examples 1 to 3 and Comparative Examples 1 to 3 on nodular goiter were investigated through drug intervention.

[0120] Test method: 80 healthy male SPF SD rats were randomly divided into a normal control group (no modeling, no medication), a model control group (modeling, no medication), and a medication group (modeling, medication, respectively recorded as the medication group of Example 1, the medication group of Example 2, the medication group of Example 3, the medication group of Comparative Example 1, the medication group of Comparative Example 2, and the medication group of Comparative Example 3), with 10 rats in each group, and the rat model of nodular goiter was modeled by propylthiouracil gavage. The medication groups were respectively given a drug suspension with a concentration of 0.05 g / mL prepared from the NAD+-containing composition provided by Examples 1 to 3 and Comparative Examples 1 to 3, and the dosage was 0.5 g / kg, once a day, for 6 consecutive weeks, and the normal control group and the model control group were given the same volume of distilled water. After the last administration, the rats in each group were fasted for 12 h but not water, and then blood was collected from the abdominal aorta after intraperitoneal injection of anesthesia. The blood was centrifuged and the serum was collected. The ELISA analysis method was used to determine the levels of thyroid stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) in the rat serum. The test results are shown in Table 1. The test results are expressed as mean ± standard deviation.

[0121] Table 1

[0122]

[0123]

[0124] As shown in Table 1, compared with the normal control group, the TSH level in the model control group was significantly increased and the FT3 and FT4 levels were significantly reduced; at the same time, after the intervention of the rat model of nodular goiter with the composition containing NAD+ provided in Examples 1 to 3, the TSH level in the model control group was significantly reduced, and the FT3 and FT4 levels were significantly increased. It shows that the composition provided by the present invention can significantly regulate the thyroid hormone level and the content of related antibodies in the model rat experiment, and the drug intervention effect is significantly better than that of Comparative Examples 1 to 3.

[0125] In summary, the embodiments of the present invention provide a composition containing NAD+ and its use. The present invention uses a suitable proportion of NAD+, alligator flower extract and narrow-lined schizonepeta extract in combination, and it is found that the composition can significantly regulate thyroid hormone levels and related antibody content in model rat experiments, and effectively alleviate the nodular condition of thyroid tissue. This discovery not only reveals the potential value of the composition in the treatment of nodular thyroid disease, but also opens up a new direction for the clinical application of NAD+, alligator flower and narrow-lined schizonepeta, and has a wide range of practical application value.

[0126] The foregoing is merely a specific embodiment of the present invention, which enables those skilled in the art to understand or implement the present invention. Various modifications to these embodiments will be apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features claimed herein.

Claims

1. A composition containing NAD+, characterized in that The NAD+-containing composition comprises the following components in parts by weight: 1-5 parts of NAD+, 16-22 parts of alligator mouth flower extract and 5-10 parts of narrow-lined schisandra extract.

2. The NAD+-containing composition according to claim 1, characterized in that The NAD+-containing composition comprises the following components in parts by weight: 3 parts of NAD+, 20 parts of alligator mouth flower extract and 8 parts of narrow-lined schisandra extract.

3. The NAD+-containing composition according to claim 1, characterized in that The alligator mouth flower extract comprises alligator mouth flower petroleum ether extract.

4. The NAD+-containing composition according to claim 3, characterized in that Preparation method of petroleum ether extract of crocodile mouth flower The process includes: The crushed crocodile mouth flower and petroleum ether are mixed in a weight ratio of 1: (5-10), and then soaked at room temperature for 5-10 days to obtain a mixture; The mixture is filtered and the obtained filter residue is continuously rinsed with petroleum ether for 1 to 3 times, and then the filtrate and the rinsing liquid are concentrated and dried under reduced pressure to obtain the petroleum ether extract of alligator flower.

5. The NAD+-containing composition according to claim 1, characterized in that The extract of Ipomoea acuta includes an aqueous extract of Ipomoea acuta.

6. The NAD+-containing composition according to claim 1, characterized in that The preparation method of the water extract of narrow-lined schizonepeta tenuifolia The process includes: The crushed whole herb of the narrow-lined sedge and water are mixed in a weight ratio of 1: (5-10), and then reflux extraction is performed to obtain an extract; The extract is concentrated under reduced pressure and dried to obtain the water extract of the Ipomoea acuta.

7. The NAD+-containing composition according to claim 6, characterized in that The working condition parameters of the reflux extraction include: temperature of 100-110° C., time of 60-90 minutes, and number of times of 1-3 times.

8. Use of the NAD+-containing composition according to any one of claims 1 to 7 in the preparation of a drug for treating nodular goiter.

9. The use according to claim 8, characterized in that: The drug for treating nodular goiter includes an effective ingredient and a pharmaceutically acceptable excipient, wherein the effective ingredient is the NAD+-containing composition according to any one of claims 1 to 7, and the pharmaceutically acceptable excipient includes at least one of a filler, a disintegrant, a lubricant, a binder and a sweetener.

10. The use according to claim 8, characterized in that: The dosage form of the drug for treating nodular goiter includes at least one of injection, powder, tablet, capsule, granule and pill.

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