Pine pollen extract containing nmn sustained-release medicine and preparation method and application thereof

Abstract

The application provides a pine pollen extract containing NMN sustained-release medicine and a preparation method and application thereof, and relates to the technical field of medicaments.The pine pollen extract containing NMN sustained-release medicine provided by the application comprises pine pollen extract, a skeleton material, a filler and a lubricant in a specific ratio.The inventor has found that the pine pollen extract is rich in a large amount of NMN and is stable in property, and the pine pollen extract sustained-release medicine prepared by combining the pine pollen extract with the skeleton material, the filler and the lubricant can control the release of the NMN effective component in the small intestine, improve the effective absorption and bioavailability of the NMN component, and achieve the effect of delaying aging.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, and in particular to a sustained-release drug of pine pollen extract containing NMN, its preparation method, and its application. Background Technology

[0002] NMN (Nicotinamide mononucleotide), β-nicotinamide mononucleotide, is a precursor to NAD+ (nicotinamide adenine dinucleotide, coenzyme I) and can be converted into NAD+ in the body. NAD+ is a very important substance in the body, present in every cell, participating in thousands of biochemical reactions, providing energy for metabolism, building new cellular components, resisting free radical damage, serving as an important raw material for repairing damaged DNA, and acting as a messenger and communication factor to transmit signals between the cell nucleus and mitochondria. Over time, the level of NAD+ in the human body decreases significantly. Studies have shown that NMN supplementation can make older mice appear and move with youthful vitality, and NMN supplementation can upregulate the expression of the sirtuins family of longevity proteins in the human body, thus delaying aging.

[0003] Natural NMN is mainly found in food. Studies have verified that foods containing NMN include edamame, broccoli, avocado, tomatoes, shiitake mushrooms, beef, and shrimp. Experimental studies have also found that pine pollen contains NMN, and in higher amounts than edamame and broccoli, making it a potential source of natural NMN. Extracts made from pine pollen can be further processed through extraction and concentration to obtain substances with even higher NMN content, making them suitable as raw materials for novel nutritional and health food products.

[0004] Most NMN products currently on the market use raw materials prepared through synthesis. While these raw materials have relatively high purity, byproducts are inevitably present during synthesis. Furthermore, purified NMN raw materials are chemically unstable and sensitive to light and oxygen, limiting the preservation of both raw materials and finished products, which is detrimental to product development, application, and promotion. Naturally derived NMN obtained through phytochemical technology avoids these problems, and natural extracts containing NMN will be the primary source of raw materials for NMN products.

[0005] The small intestine is the main site of NMN absorption. Conventional oral preparations, such as tablets and capsules, suffer some loss after oral administration and before reaching the small intestine through the digestive system, thus failing to achieve full and effective absorption and utilization.

[0006] In view of this, the present invention is hereby proposed. Summary of the Invention

[0007] The primary objective of this invention is to provide a sustained-release pine pollen extract containing NMN, thereby addressing at least one of the aforementioned problems.

[0008] The second objective of this invention is to provide a method for preparing the above-mentioned sustained-release drug containing NMN pine pollen extract.

[0009] A third objective of this invention is to provide the application of the above-mentioned NMN-containing pine pollen extract sustained-release drug in the preparation of anti-aging drugs.

[0010] In a first aspect, the present invention provides a sustained-release pine pollen extract containing NMN, comprising the following components by weight: 40-60 parts of pine pollen extract, 25-40 parts of matrix material, 5-15 parts of filler and 2-8 parts of lubricant.

[0011] As a further technical solution, the following components are included by weight: 45-55 parts of pine pollen extract, 30-35 parts of skeleton material, 5-8 parts of filler and 2-4 parts of lubricant;

[0012] Preferably, it comprises the following components by weight: 50 parts pine pollen extract, 30 parts skeleton material, 8 parts filler and 4 parts lubricant.

[0013] As a further technical solution, the pine pollen extract includes pine pollen water extract;

[0014] Preferably, the method for preparing the pine pollen water extract includes: extracting broken-cell pine pollen with water, and then preparing the pine pollen water extract after solid-liquid separation and drying.

[0015] Preferably, the mass ratio of the broken-cell pine pollen to water is 1:10-1:40;

[0016] Preferably, the extraction is performed under ultrasonic conditions;

[0017] Preferably, the ultrasonic power is 300-500W, the ultrasonic temperature is 30-60℃, and the ultrasonic time is 20-60min;

[0018] Preferably, the solid-liquid separation includes centrifugation or filtration;

[0019] Preferably, a filter membrane with a density of 1000-100000 Da is used for filtration.

[0020] As a further technical solution, each gram of pine pollen extract contains 10-20 μg of NMN.

[0021] As a further technical solution, the skeleton material includes hydroxypropyl methylcellulose (HPMC);

[0022] Preferably, the hydroxypropyl methylcellulose includes at least one of HPMC K15M, HPMC K100M, and HPMC K200M.

[0023] As a further technical solution, the filler includes microcrystalline cellulose.

[0024] As a further technical solution, the lubricant includes at least one of magnesium stearate or talc.

[0025] As a further technical solution, the dosage form of the NMN-containing pine pollen extract sustained-release drug includes tablets.

[0026] Secondly, the present invention provides a method for preparing a sustained-release drug of pine pollen extract containing NMN, comprising: mixing the pine pollen extract, a matrix material and a filler, granulating the mixture, then mixing it with a lubricant and compressing it into tablets to prepare a sustained-release drug of pine pollen extract containing NMN.

[0027] Thirdly, the present invention provides the application of a sustained-release drug of pine pollen extract containing NMN in the preparation of anti-aging drugs.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] The present invention provides a sustained-release pine pollen extract containing NMN, comprising a specific ratio of pine pollen extract, a matrix material, a filler, and a lubricant. The inventors have discovered that pine pollen extract is rich in NMN and has stable properties. The sustained-release pine pollen extract prepared in combination with the matrix material, filler, and lubricant can control the release of NMN active ingredients upon reaching the small intestine, improving the effective absorption and bioavailability of NMN, thus achieving anti-aging effects. Attached Figure Description

[0030] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0031] Figure 1 The NMN dissolution rate curve in pine pollen extract sustained-release tablets;

[0032] Figure 2 The NMN dissolution rate curve of pine pollen extract sustained-release tablets in artificial gastric fluid. Detailed Implementation

[0033] The embodiments and examples of the present invention will be described in detail below. However, those skilled in the art will understand that the following embodiments and examples are for illustrative purposes only and should not be considered as limiting the scope of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention. Unless otherwise specified, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all commercially available conventional products.

[0034] In a first aspect, the present invention provides a sustained-release pine pollen extract containing NMN, comprising the following components by weight: 40-60 parts of pine pollen extract, 25-40 parts of matrix material, 5-15 parts of filler and 2-8 parts of lubricant.

[0035] In this invention, the pine pollen extract is obtained by extracting pine pollen as raw material. By weight, the pine pollen extract can be, for example, but not limited to, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58 or 60 parts; the skeleton material can be, for example, but not limited to, 25 parts, 26 parts, 28 parts, 30 parts, 32 parts, 34 parts, 36 parts, 38 parts or 40 parts; the filler can be, for example, but not limited to, 5 parts, 7 parts, 9 parts, 11 parts, 13 parts or 15 parts; and the lubricant can be, for example, but not limited to, 2 parts, 3 parts, 4 parts, 5 parts, 6 parts, 7 parts or 8 parts.

[0036] The NMN-containing pine pollen extract sustained-release drug provided by this invention, through the synergistic effect of its various components, can control the release of NMN active ingredients at the point of reaching the small intestine, thereby improving the effective absorption and bioavailability of NMN and achieving the effect of delaying aging.

[0037] In some preferred embodiments, the product includes the following components by weight: 45-55 parts pine pollen extract, 30-35 parts skeleton material, 5-8 parts filler, and 2-4 parts lubricant;

[0038] Preferably, it comprises the following components by weight: 50 parts pine pollen extract, 30 parts skeleton material, 8 parts filler and 4 parts lubricant.

[0039] By further optimizing and adjusting the various components in the sustained-release drug of pine pollen extract containing NMN, NMN begins to be released upon reaching the small intestine, thereby improving the effective absorption of NMN.

[0040] In some preferred embodiments, the pine pollen extract includes an aqueous extract of pine pollen.

[0041] The inventors discovered that the pine pollen extract obtained by water extraction has a high NMN content. Therefore, the water extract of pine pollen is preferred as a sustained-release drug for preparing NMN from pine pollen extract.

[0042] This invention does not impose specific limitations on the preparation method of water extracts of pollen. For example, the preparation method of water extracts of pine pollen is as follows:

[0043] After removing sand and impurities, pine pollen is broken down using low-temperature high-speed cyclone technology to obtain broken-cell pine pollen.

[0044] Broken-cell pine pollen and distilled water were mixed at a ratio of 1:(10-40), and ultrasonicated at 300-500w and 40-60℃ for 30-60 minutes. The mixture was then filtered, and the filtrate was concentrated by ultrafiltration with a membrane of 1000Da-100000Da. The filtrate with a molecular weight of less than 1000Da-5000Da was collected. The filtrate was distilled under reduced pressure to obtain a paste, and the paste was freeze-dried to obtain the extract.

[0045] In some preferred embodiments, each gram of pine pollen extract may contain NMN, for example, but not limited to, 10ug, 12ug, 14ug, 16ug, 18ug, or 20ug.

[0046] In some preferred embodiments, the skeleton material includes hydroxypropyl methylcellulose.

[0047] Hydroxypropyl methylcellulose (HMC) is a hydrophilic sustained-release drug carrier, soluble in gastrointestinal fluids. It possesses excellent compressibility, flowability, and drug-carrying capacity, making it a crucial hydrophilic carrier material in sustained-release formulations. By adjusting its viscosity, HMC can achieve precise drug release. High-viscosity HMC hydrates rapidly, has strong absorption capacity, and forms a high-viscosity gel layer. Consequently, drug diffusion through the gel layer is slow, and gel layer dissolution is also slow, providing strong protection for the drug. The drug release characteristics of HMC are unaffected by pH, thus it can protect the drug from gastric juices, ensuring that it is not released into the stomach for a short period.

[0048] Preferably, the hydroxypropyl methylcellulose includes at least one of HPMC K15M, HPMC K100M, and HPMC K200M.

[0049] In some preferred embodiments, the filler comprises microcrystalline cellulose.

[0050] Microcrystalline cellulose is a commonly used excipient and filler in pharmaceuticals. Its good flowability and adhesive properties simplify the tablet manufacturing process and improve production efficiency. The unique hydrogen bonds between microcrystalline cellulose molecules can also serve as an auxiliary material in the tablet matrix, contributing to sustained-release effects.

[0051] In some preferred embodiments, the lubricant includes at least one of magnesium stearate or talc.

[0052] Magnesium stearate and talc are common excipients in pharmaceutical tablet formulations, used as lubricants to improve the flowability of powdered drugs and make tablets smooth and aesthetically pleasing. Magnesium stearate and talc have a wide range of applications in pharmaceutical tablet formulations and have a solid foundation for use. In the special dosage form preparation process of sustained-release tablets, they are excellent auxiliary materials used to enhance tablet stability.

[0053] In some preferred embodiments, the dosage form of the NMN-containing pine pollen extract sustained-release drug includes tablets.

[0054] Secondly, the present invention provides a method for preparing a sustained-release drug of pine pollen extract containing NMN, comprising: mixing the pine pollen extract, a matrix material and a filler, granulating the mixture, then mixing it with a lubricant and compressing it into tablets to prepare a sustained-release drug of pine pollen extract containing NMN.

[0055] The preparation method is simple and convenient, and the resulting sustained-release pine pollen extract containing NMN has high dissolution rate. It can control the release of NMN active ingredients at the small intestine, thereby improving the effective absorption of NMN.

[0056] Thirdly, the present invention provides the application of a sustained-release drug of pine pollen extract containing NMN in the preparation of anti-aging drugs.

[0057] The sustained-release pine pollen extract provided by this invention contains NMN and has good anti-aging effects.

[0058] The present invention will be further illustrated below with specific embodiments and comparative examples. However, it should be understood that these embodiments are merely for the purpose of more detailed illustration and should not be construed as limiting the present invention in any way.

[0059] Example 1

[0060] A sustained-release tablet containing NMN, made from pine pollen extract:

[0061] Main ingredient: 50 parts pine pollen extract; auxiliary ingredients: 5 parts HPMC K15M skeleton material, 30 parts HPMC K100M; filler: 6 parts microcrystalline cellulose; lubricant: 2 parts magnesium stearate.

[0062] The preparation method of sustained-release tablets is as follows:

[0063] Pine pollen extract, microcrystalline cellulose, and hydroxypropyl methylcellulose are mixed evenly and then granulated.

[0064] Mix the granulated granules with the lubricant magnesium stearate evenly, and compress into tablets at a rate of 500 mg / tablet.

[0065] Example 2

[0066] A sustained-release tablet containing NMN, made from pine pollen extract:

[0067] Main ingredient: 50 parts pine pollen extract; auxiliary ingredients: 30 parts HPMC K100M and 5 parts HPMC K200M skeleton materials; filler: 5 parts microcrystalline cellulose; lubricant: 4 parts magnesium stearate.

[0068] The preparation method is the same as in Example 1.

[0069] Example 3

[0070] A sustained-release tablet containing NMN, made from pine pollen extract:

[0071] Main ingredient: 50 parts pine pollen extract; auxiliary ingredients: 25 parts HPMC K100M skeleton material, 5 parts HPMC K200M; filler: 8 parts microcrystalline cellulose; lubricant: 2 parts talc.

[0072] The preparation method is the same as in Example 1.

[0073] Example 4

[0074] A sustained-release tablet containing NMN, made from pine pollen extract:

[0075] Main ingredient: 50 parts pine pollen extract; auxiliary ingredients: 30 parts HPMC K100M skeleton material, 8 parts microcrystalline cellulose filler, and 4 parts magnesium stearate lubricant.

[0076] The preparation method is the same as in Example 1.

[0077] Example 5

[0078] A sustained-release tablet containing NMN, made from pine pollen extract:

[0079] Main ingredient: 60 parts pine pollen extract; auxiliary ingredients: 25 parts HPMC K15M skeleton material, 15 parts microcrystalline cellulose filler, and 2 parts magnesium stearate lubricant.

[0080] The preparation method is the same as in Example 1.

[0081] Example 6

[0082] A sustained-release tablet containing NMN, made from pine pollen extract:

[0083] Main ingredient: 40 parts pine pollen extract; auxiliary ingredients: 40 parts HPMC K100M skeleton material, 5 parts microcrystalline cellulose filler, and 8 parts magnesium stearate lubricant.

[0084] The preparation method is the same as in Example 1.

[0085] Comparative Example 1

[0086] A sustained-release tablet containing NMN, made from pine pollen extract:

[0087] Main ingredient: 50 parts pine pollen extract; auxiliary ingredients: 50 parts HPMC K100M skeleton material, 1 part microcrystalline cellulose filler, and 15 parts magnesium stearate lubricant.

[0088] The preparation method is the same as in Example 1.

[0089] Comparative Example 2

[0090] A sustained-release tablet containing NMN, made from pine pollen extract:

[0091] Main ingredient: 50 parts pine pollen extract; auxiliary ingredients: 15 parts HPMC K100M skeleton material, 25 parts microcrystalline cellulose filler, and 1 part magnesium stearate lubricant.

[0092] The preparation method is the same as in Example 1.

[0093] Comparative Example 3

[0094] A sustained-release tablet containing NMN, made from pine pollen extract:

[0095] The difference from Example 1 is that the skeleton material is 15 parts of sodium carboxymethyl cellulose (CMC-Na).

[0096] Comparative Example 4

[0097] A sustained-release tablet containing NMN, made from pine pollen extract:

[0098] The difference from Example 1 is that the filler is 6 parts lactose.

[0099] Comparative Example 5

[0100] A sustained-release tablet containing NMN, made from pine pollen extract:

[0101] The difference from Example 1 is that the lubricant is 2 parts of polyethylene glycol (PEG6000).

[0102] Experimental Example 1

[0103] NMN dissolution experiment in sustained-release tablets

[0104] Experimental methods: Samples from each example were taken and dissolved according to the method of dissolution and release determination (Chinese Pharmacopoeia 2015 Edition, Part IV, General Chapter 0931, Method I), using 1000 mL of water as the dissolution medium and a rotation speed of 50 rpm. At 4 hours, 8 hours, and 12 hours, 10 mL of solution was taken, filtered, and 1 mL of the filtrate was accurately measured. The NMN content was determined by LC-MS, and the dissolution rate (cumulative dissolution rate) of each tablet at different times was calculated.

[0105] The NMN dissolution rate curves for each embodiment are attached. Figure 1 .

[0106] Experimental Example 2

[0107] Dissolution experiment of NMN in sustained-release tablets in simulated gastric juice

[0108] Experimental methods: Samples from each example were taken and dissolved according to the method of dissolution and release determination (Chinese Pharmacopoeia 2015 Edition, Part IV, General Chapter 0931, Method I), using artificial gastric fluid as the dissolution medium, rotating at 50 revolutions per minute, and at the 1-hour time point, 10 ml of solution was taken, filtered, and 1 ml of filtrate was accurately measured. The NMN content was determined by LC-MS method, and the dissolution rate (cumulative dissolution rate) of each tablet at different times was calculated.

[0109] Dissolution rate curves for each example are attached. Figure 2 .

[0110] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A sustained-release drug containing NMN pine pollen extract, characterized in that, It includes the following components by weight: 40-60 parts pine pollen extract, 25-40 parts skeleton material, 5-15 parts filler and 2-8 parts lubricant; The pine pollen extract is a water-based extract of pine pollen. The preparation method of the water-based pine pollen extract includes: extracting cell-wall-broken pine pollen with water, followed by solid-liquid separation and drying to obtain the water-based pine pollen extract; the extraction is performed under ultrasonic conditions; the ultrasonic power is 300-500 W, the ultrasonic temperature is 30-60℃, and the ultrasonic time is 20-60 min; the solid-liquid separation is performed using a 1000-100000 Da filter membrane. The skeleton material is at least one of hydroxypropyl methylcellulose HPMC K15M, HPMC K100M, and HPMC K200M; the dosage form of the NMN-containing pine pollen extract sustained-release drug is a tablet.

2. The sustained-release pine pollen extract containing NMN according to claim 1, characterized in that, It includes the following components by weight: 45-55 parts pine pollen extract, 30-35 parts skeleton material, 5-8 parts filler and 2-4 parts lubricant.

3. The sustained-release pine pollen extract containing NMN according to claim 1, characterized in that, It includes the following components by weight: 50 parts pine pollen extract, 30 parts skeleton material, 8 parts filler and 4 parts lubricant.

4. The sustained-release pine pollen extract containing NMN according to claim 1, characterized in that, The mass ratio of the broken-cell pine pollen to water is 1:10-1:

40.

5. The sustained-release pine pollen extract containing NMN according to claim 1, characterized in that, Each gram of pine pollen extract contains 10-20 ug of NMN.

6. The sustained-release pine pollen extract containing NMN according to claim 1, characterized in that, The filler includes microcrystalline cellulose.

7. The sustained-release pine pollen extract containing NMN according to claim 1, characterized in that, The lubricant includes at least one of magnesium stearate or talc.

8. The method for preparing the sustained-release drug containing NMN pine pollen extract according to any one of claims 1-7, characterized in that, include: The pine pollen extract, skeleton material, and filler are mixed and granulated, then mixed with a lubricant and compressed into tablets to prepare a sustained-release drug of pine pollen extract containing NMN.

9. The use of the NMN-containing pine pollen extract sustained-release drug according to any one of claims 1-7 or the NMN-containing pine pollen extract sustained-release drug prepared by the preparation method according to claim 8 in the preparation of anti-aging drugs.

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