阅读说明：本技术 含nmn的益智健脑药物组合物 (NMN-containing pharmaceutical composition for improving intelligence and strengthening brain ) 是由 沈洁 于 2020-07-02 设计创作，主要内容包括：一种用于干预轻度认知功能损害的药物组合物,由NMN、高山火绒草提取物以及药学上可接受的辅料组成,其中高山火绒草提取物能显著降低NMN在干预轻度认知损害中的用药浓度。(A pharmaceutical composition for intervening mild cognitive impairment comprises NMN, a Leontopodium alpinum extract and pharmaceutically acceptable auxiliary materials, wherein the Leontopodium alpinum extract can remarkably reduce the administration concentration of the NMN for intervening mild cognitive impairment.)

1. A pharmaceutical composition comprises NMN, a Hibiscus alpine Leontopodium extract and pharmaceutically acceptable auxiliary materials, and is characterized in that the preparation of the Hibiscus alpine Leontopodium extract comprises the following steps:

1) pretreating fresh grass of the alpine edelweiss or cell culture of the fresh alpine edelweiss by using lower alcohol ultrasonic;

2) leaching the pretreatment product of the step 1) with high-temperature water, and centrifuging or filtering the leaching product to obtain solution A;

3) soxhlet extracting the dry powder of the alpine edelweiss with lower alcohol to obtain solution B;

4) mixing the solution A and the solution B at equal ratio, concentrating under reduced pressure, and lyophilizing to obtain the extract of herba Leontopodii Adoratae.

2. The pharmaceutical composition of claim 1, wherein the ratio of NMN: the mass part ratio of the alpine edelweiss extract is 1-10: 10-1000.

3. A pharmaceutical composition according to claim 1 or 2, wherein the NMN: the mass part ratio of the edelweiss extract is 1-2: 500-800.

4. A pharmaceutical composition according to claim 1 or 2, wherein the NMN: the mass part ratio of the alpine edelweiss extract is 1-2: 600.

5. A method for preparing a pharmaceutical composition, comprising the steps of:

1) adding 2 times volume of lower alcohol into 1 part of fresh grass powder or cell culture of the fresh grass (the material-liquid ratio is 1:2(m/v)) of the alpine edelweiss, and performing 200-300W ultrasonic pretreatment for 10-30min at 25-30 ℃;

2) adding 5-10 times of pure water into the ultrasonic pretreatment product, leaching for 1-2h at 80-120 ℃, and centrifuging or filtering the leaching product to obtain solution A;

3) adding 10-20 times of lower alcohol into 1 part of the dry grass powder of the alpine edelweiss by mass, and performing Soxhlet extraction until the solution is colorless to obtain solution B;

4) mixing A, B solutions in equal volume, concentrating under reduced pressure, and lyophilizing to obtain herba Leontopodii Adoratae extract;

5) weighing NMN with formula amount, and mixing with the extract of the leontopodium alpinum in equal ratio;

6) adding a proper amount of pharmaceutically acceptable auxiliary material preparation on the basis of the mixture and forming.

6. The method as claimed in claim 5, wherein the powder of the fresh grass of alpine edelweiss is prepared within 10-30min before the ultrasonic pretreatment.

7. The method of claim 5, wherein the fine powder of Hibiscus sabdariffa is soaked before alcohol extraction.

8. The method according to claim 5, wherein the lower alcohol used in the process for preparing the extract of Leontopodium alpinum is ethanol or butanediol.

9. The method according to claim 5, wherein the lower alcohol used in the process for preparing the extract of Leontopodium alpinum is ethanol.

10. A pharmaceutical composition comprises NMN, an extract of edelweiss and pharmaceutically acceptable auxiliary materials, and is characterized in that the pharmaceutical composition is used for intervening mild cognitive impairment.

Technical Field

The invention belongs to the technical field of medicines, and particularly provides an NMN-containing brain-strengthening medicine composition for inhibiting mild cognitive function damage caused by oxidative stress.

Background

Mild Cognitive Impairment (MCI) refers to a transitional stage of cognitive impairment between normal aging and Alzheimer's Disease (AD) at the same age and education, the main cause of which is the inevitable Oxidative Stress (OS) injury of the body. Therefore, antioxidant treatment of the body is a major clinical means for preventing and inhibiting MCI.

However, after the clinical findings that the damage caused by improving oxidative stress by using conventional antioxidants such as vitamin C, vitamin E and β -carotene has little effect, research on the extraction, function and mechanism of natural antioxidants such as resveratrol and stilbene glucoside begins, and although certain effects are achieved, in the clinical process, individual differences exist between the action target and the administration concentration, especially the concentration of the antioxidant substances after passing through the blood brain barrier cannot be guaranteed, so that large-scale clinical application is difficult.

Research shows that NMN (Nicotinamide mononucleotide) can activate Nampt-NAD defense system, protect cranial nerve, promote blood vessel and nerve regeneration, protect cerebral hemorrhage and nerve injury converted from cerebral hemorrhage, and is a potential anti-stroke medicine. The action mechanism is that NMN can reduce the content of hemoglobin in infarcted tissues, reduce bleeding and edema and reduce the brain tissue oxidative toxicity damage caused by oxidative stress. However, it does not prove that NMN inhibits the body's inevitable OS damage during natural aging; more importantly, the process of OS damage associated with aging is slow, sustained, and does not produce acute, massive damage from bleeding, and thus its concentration, mode, and pharmacology must be naturally different.

Disclosure of Invention

The invention provides an NMN-containing pharmaceutical composition for improving intelligence and strengthening brain, which is used for inhibiting mild cognitive function damage caused by oxidative stress. The invention also provides a preparation method of the NMN-containing pharmaceutical composition for benefiting intelligence and strengthening brain.

The invention provides a pharmaceutical composition, which consists of NMN, a Hibiscus sabdariffa extract and pharmaceutically acceptable auxiliary materials.

Preferably, in the pharmaceutical composition of the present invention, the ratio of NMN: the mass part ratio of the alpine edelweiss extract is 1-10: 10-1000;

more preferably, in the pharmaceutical composition of the present invention, the ratio of NMN: the mass part ratio of the edelweiss extract is 1-2:500-800, for example, 1-2: 600.

Further, the extraction method of the leontopodium alpinum extract in the pharmaceutical composition of the invention comprises the following steps:

1) pretreating fresh grass of the alpine edelweiss or cell culture of the fresh alpine edelweiss by using lower alcohol ultrasonic;

2) leaching the pretreatment product of the step 1) with high-temperature water, and centrifuging or filtering the leaching product to obtain solution A;

3) soxhlet extracting the dry powder of the alpine edelweiss with lower alcohol to obtain solution B;

4) mixing the solution A and the solution B at equal ratio, concentrating under reduced pressure, and lyophilizing to obtain the extract of herba Leontopodii Adoratae.

Furthermore, the pharmaceutical composition is prepared by mixing the NMN and the extract of the leontopodium alpinum according to the mass fraction ratio.

Further, the preparation method of the edelweiss extract in the pharmaceutical composition comprises the following steps:

1) adding 2 times volume of lower alcohol into 1 part of fresh grass powder or cell culture of the fresh grass (the material-liquid ratio is 1:2(m/v)) of the alpine edelweiss, and performing 200-300W ultrasonic pretreatment for 10-30min at 25-30 ℃;

2) adding 5-10 times of pure water into the ultrasonic pretreatment product, leaching for 1-2h at 80-120 ℃, and centrifuging or filtering the leaching product to obtain solution A;

3) adding 10-20 times of lower alcohol into 1 part of the dry grass powder of the alpine edelweiss by mass, and performing Soxhlet extraction until the solution is colorless to obtain solution B;

4) mixing A, B solutions in equal volume, concentrating under reduced pressure, and lyophilizing to obtain herba Leontopodii Adoratae extract.

Furthermore, the powder of the Hibiscus cannabifolius Linn in the pharmaceutical composition of the invention needs to be prepared within 10-30min before ultrasonic pretreatment.

Furthermore, the alpine fire hay powder in the pharmaceutical composition of the present invention should be soaked before alcohol extraction.

Furthermore, the lower alcohol used in the preparation process of the leontopodium alpinum extract in the pharmaceutical composition of the invention is ethanol or butanediol.

Preferably, the lower alcohol used in the preparation process of the extract of leontopodium alpinum is ethanol.

Further, the pharmaceutical composition provided by the invention comprises NMN and the extract of the leontopodium alpinum. The pharmaceutical composition refers to a composition with medical activity for preparing a medicament, and comprises a proper amount of pharmaceutically acceptable auxiliary materials besides the medical active composition.

Furthermore, the pharmaceutical composition also comprises NMN which is weighed according to the formula amount and is mixed with the extract of the leontopodium alpinum in equal proportion, and after mixing, a proper amount of pharmaceutically acceptable auxiliary material preparation is added for forming.

In the present invention, the term "pharmaceutically acceptable excipient" includes pharmaceutically acceptable carriers, excipients, diluents and the like, which are compatible with the pharmaceutically active ingredient. The use of pharmaceutically acceptable excipients for the preparation of pharmaceutical preparations is well known to those skilled in the art.

The pharmaceutical composition of the present invention comprises the NMN and leontopodium alpinum extract composition of the present invention as an active ingredient, and the composition is combined with pharmaceutically acceptable adjuvants (such as carriers, excipients, diluents, etc. well known to those of ordinary skill in the art) to be formulated into various formulations, preferably solid formulations and liquid formulations, such as tablets, pills, capsules, powders, suspensions, granules, syrups, emulsions, suspensions, etc., and various sustained release formulations, preferably in oral administration form.

In a particular embodiment of the invention, for the inhibition of mild cognitive impairment caused by oxidative stress, the dose, expressed as nicotinamide mononucleotide, is 5-10ng/kg body weight per day.

In the specific embodiment of the invention, the plant cells of the fresh grass of the alpine edelweiss and the cultured alpine edelweiss are equivalent and can be replaced with each other.

In the specific embodiment of the invention, the alpine edelweiss hay is powder which is naturally air-dried, freeze-dried or processed by drying and then crushed.

In the embodiment of the present invention, the powder of alpine edelweiss means grass clippings having a particle size of 0.5cm or less.

In a specific embodiment of the present invention, the total volume of liquid added for the same batch of hay and fresh grass extractions is about 2: 1.

In a particular embodiment of the invention, the lower alcohol used for the ultrasonic pretreatment is preferably ethanol, which is replaced by the same mass or volume of butanediol, without affecting the process effect.

In the embodiment of the present invention, the ultrasonic extraction conditions can be adjusted within the range given in the present invention according to the ultrasonic effect.

The pharmaceutical composition prepared by the invention is used for intervening in mild cognitive impairment.

The inventor finds that the edelweiss mainly contain bioactive substances such as leontopodic acid, chlorogenic acid, flavone, caffeoylquinic acid, phenols and the like; in the process of drying or freezing the alpine edelweiss, active ingredients of cells, particularly flavone, chlorogenic acid or caffeoylquinic acid substances, are greatly lost due to a treatment process or self enzymolysis, and even are difficult to obtain by a conventional extraction process; meanwhile, the effective components and contents in the extract show significant differences with different extraction processes. The efficacy of the different extracts in inhibiting mild cognitive impairment caused by oxidative stress also differed significantly after compatibility with NMN. The optimal effect of inhibiting mild cognitive function damage caused by oxidative stress can be obtained by matching NMN with a proper proportion on the basis of comprehensively utilizing water-extracted fresh leontopodium alpinum grass powder or a fresh leontopodium alpinum cell culture and alcohol-extracted leontopodium alpinum hay powder.

Detailed Description

Hereinafter, specific embodiments of the present invention will be described in detail. Well-known structures or functions may not be described in detail in the following embodiments in order to avoid unnecessarily obscuring the details. Unless defined otherwise, technical and scientific terms used in the following examples have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.