CN112386630A - Brain-strengthening and intelligence-improving composition and preparation method and medical application thereof - Google Patents

Abstract

The invention relates to a brain-strengthening and intelligence-improving composition, a preparation method and medical application thereof. Animal experiments prove that the composition has obvious improvement effect on sleep disorder and depression.

Description

Brain-strengthening and intelligence-improving composition and preparation method and medical application thereof

Technical Field

The invention relates to a brain-strengthening and intelligence-improving composition, a preparation method and medical application thereof.

Background

Acer truncatum Bunge (academic name: Acer truncatum Bunge), alias:acer truncatumAnd color trees. Belong toAceraceae (Aceraceae)The height of the acer deciduous tree is 8-10 m; the bark is longitudinally split. A single leaf; single leaf generation; 5 pulses are treated; a palm shape; the petiole is 3-5 cm long. Growing the inflorescence of the umbrella house; yellow and green. The flowering period is 5 months, and the fruit period is 9 months. The acer truncatum has beautiful appearance, beautiful leaf shape and red tender leaf, and leaves in autumn turn become yellow or red, which is a famous red-leaf tree species in autumn. Widely growing in yellow river and downstream provinces, in the south of the east and the north of Jiangsu, and in the south of Anhui, there are many hills and flat lands in low mountains with elevation below 800 m. The acer truncatum seeds are mature fruits of acer truncatum, the oil content can reach 40-45%, and the acer truncatum seeds oil is listed in the New resources food catalog by the national ministry of health in 2011. In recent years, the acer truncatum seed oil is found to contain nervonic acid which is an active substance for the nervous system, and further causes development and development of a hot tide.

Polygala tenuifolia Willd, also known as \33917, Juanjiao, 34112, 33964c, etc.. Is a traditional Chinese medicine loaded in the first part of Chinese pharmacopoeia 2015 edition. Polygala tenuifolia is produced in northeast, north China, northwest, China and Sichuan; perennial herbs, strong and strong taproots, and phloem flesh. Has the functions of soothing nerves, benefiting intelligence, eliminating phlegm and reducing swelling, and is used for treating insomnia, dreaminess, amnesia, palpitation, absentmindedness, expectoration, sore and ulcer, swelling and toxin, breast swelling and pain and the like caused by imbalance between heart-yang and kidney-yin.

The invention creatively combines polygala tenuifolia and acer truncatum, and finds that the pharmaceutical and clinical effects of improving sleep and depression are good.

Disclosure of Invention

According to a first aspect of the present invention, there is provided a brain-strengthening and intelligence-improving composition comprising:

90-10 wt% of acer truncatum seed extract,

preferably 80 to 20 wt%, more preferably 60 to 40 wt%;

10-90 wt% of polygala root extract,

preferably 20-80 wt%, more preferably 40-60 wt%, based on the total mass of acer truncatum seed extract and polygala tenuifolia extract.

In one embodiment, the acer truncatum seed extract is an extract obtained by extracting acer truncatum seeds with an alcohol, ether, saturated alkane (e.g., absolute ethanol, methyl ethyl ether, heptane). The chemical composition of the compound is mainly fatty acid ester accounting for 30-40 percent, and comprises, for example, 29.0.0-32 percent by weight of linoleic acid, 14.0-17.0 percent by weight of oleic acid and 4.5-6.0 percent by weight of nervonic acid. The Acer truncatum seed extract can be extracted by conventional method or purchased from market.

In one embodiment, the polygala tenuifolia extract is an extract obtained by extracting polygala tenuifolia serving as a traditional Chinese medicine raw material with any one of alcohol, ether and saturated alkane (such as absolute ethyl alcohol, methyl ethyl ether and heptane). The chemical composition of the compound is mainly fatty acid ester, and accounts for 3% -5%, and comprises 21.0-23.0 wt% of caproic acid, 6.0-6.5 wt% of phenethyl alcohol and 5.0-6.0 wt% of n-dodecyl diethanol amine. The polygala tenuifolia extract can be extracted according to a conventional extraction method.

In another embodiment, the acer truncatum seed extract is prepared by the steps of:

A) extracting Acer Truncatum Bunge seed with one of alcohol, ether, and saturated alkane under heating (such as 70-90 deg.C);

B) recovering solvent under reduced pressure to obtain extract.

In another embodiment, the polygala tenuifolia extract is prepared by the steps of:

A) extracting Acer Truncatum Bunge seed with one of alcohol, ether, and saturated alkane under heating (such as 70-90 deg.C);

B) recovering solvent under reduced pressure to obtain extract.

The compositions of the present invention may additionally comprise suitable amounts of adjuvants known in the art, such as excipients, lubricants, sweeteners, and the like.

The above-mentioned composition of the present invention can be prepared into dosage forms suitable in the art, such as tablets, pills, granules, oral liquids, and the like, using known preparation methods.

In one embodiment, the composition of the present invention is formulated as a drop pill.

The preparation method of the dripping pill comprises the following specific steps:

weighing Acer Truncatum Bunge seed extract and cortex et radix Polygalae extract, adding appropriate amount of anhydrous ethanol, slightly heating for dissolving, adding the dissolved solution into PEG6000-4000 molten liquid (58-65 deg.C, such as 60 deg.C water bath heat preservation), stirring and mixing well until ethanol is completely volatilized, standing in water bath for heat preservation for a period of time (such as 60 deg.C water bath heat preservation for 30min), removing bubbles to obtain medicine and adjuvants;

transferring the uniformly mixed molten liquid of the medicines and the auxiliary materials into a liquid storage barrel of a pill dropping machine, controlling the dropping speed under the condition of keeping the temperature at 80-85 ℃, dropping the molten liquid into the condensate drop by drop until the molten liquid is completely condensed, pouring off the condensate, collecting the dropping pills, draining, removing the condensate on the pills by using filter paper, and drying.

The invention also aims to provide the application of the composition in preparing medicines for treating depression and sleep disorder.

The invention has the advantages that:

firstly, effective substances (with small toxic and side effects) for improving sleep and depression are extracted from acer truncatum extract and polygala tenuifolia; secondly, the formula dosage is determined according to the scientific proportion (the effect is good); thirdly, the prepared dripping pill preparation is easy to be absorbed by human bodies (has high bioavailability).

Drawings

Figure 1 is a GC-map of acer truncatum oil (retention time 23.907 for nervonic acid).

Detailed Description

The invention is further illustrated by the following examples.

Example 1

Preparation of acer truncatum seed extract

Taking 500g of acer truncatum seeds, crushing, and sieving by a 40-mesh sieve; adding 3 times (W/W) of ethanol into the sieved sample, heating and refluxing at 78 deg.C for 1 hr, repeating for 4 times, and mixing extractive solutions; centrifuging the extractive solution to obtain supernatant. Concentrating under reduced pressure at 60 deg.C to obtain 105g of brown Acer Truncatum Bunge seed ethanol extract; adding the extract, heating, drying, pulverizing, sieving with 40 mesh sieve, adding 300ML petroleum ether (boiling range of 60-90 deg.C), reflux extracting, repeating for 3 times, and mixing extractive solutions; filtering the extractive solution with slow speed filter paper, and concentrating under reduced pressure at 45 deg.C to obtain Acer Truncatum Bunge extract 50.6g (about 10%). By gas chromatography (fig. 1), the composition is mainly: linoleic acid is more than or equal to 30.0%, oleic acid is more than or equal to 15.0%, nervonic acid is more than or equal to 5.0%, and the like.

Example 2

Preparation of Polygala tenuifolia extract

Taking 500g of polygala tenuifolia, crushing, and sieving by a 40-mesh sieve; adding 3 times (W/W) of ethanol into the sieved sample, heating and refluxing at 78 deg.C for 1 hr, repeating for 4 times, and mixing extractive solutions; centrifuging the extractive solution to obtain supernatant. Concentrating under reduced pressure at 60 deg.C to obtain 50g of brown cortex et radix Polygalae ethanol extract; adding the extract, heating, drying, pulverizing, sieving with 40 mesh sieve, adding 150ML petroleum ether (boiling range of 60-90 deg.C), reflux extracting, repeating for 3 times, and mixing extractive solutions; filtering the extractive solution with slow filter paper, and concentrating under reduced pressure at 45 deg.C to obtain 25.8g (about 5%) of cortex et radix Polygalae extract. The composition of the product is mainly analyzed by gas chromatography: caproic acid is more than or equal to 21.5 percent, phenethyl alcohol is more than or equal to 6.2 percent, n-dodecyl diethanolamine is more than or equal to 5.2 percent, and the like.

Example 3

Preparation of composition dripping pill

The acer truncatum seed extract and the polygala tenuifolia extract prepared in example 1 and example 2 were taken.

Preparing the medicine and the auxiliary materials: weighing 50g of Acer truncatum seed extract and 10g of Polygala tenuifolia extract, adding appropriate amount of anhydrous ethanol, slightly heating to dissolve, adding 180g of PEG6000 and 20g of beta-cyclodextrin, and heating to melt. Adding into molten liquid (60 deg.C water bath for heat preservation), stirring, mixing, standing in 60 deg.C water bath for heat preservation for 30min until ethanol is completely volatilized (no alcohol smell), and removing bubbles to obtain medicine and adjuvants.

And transferring the uniformly mixed molten liquid of the medicines and the auxiliary materials into a liquid storage barrel of a pill dropping machine, controlling the dropping speed under the condition of keeping the temperature at 80-85 ℃, dropwise dropping the molten liquid into condensate liquid, pouring out the condensate liquid after complete condensation, collecting the dropping pills, draining, removing the condensate liquid on the pills by using filter paper, placing the dropping pills in a silica gel dryer for 24 hours, weighing, and calculating the yield to obtain 9000 pills (test products) of the patent, wherein the contents are 30 mg/pill.

Quality inspection: (1) the appearance should be spherical, uniform in size and consistent in color. (2) Weight difference: weighing 20 pills, precisely weighing the pills to obtain the average pill weight, and precisely weighing each pill. Compared with the average pill weight, the pill weight exceeding the weight difference limit is not more than 2 pills, and one pill does not exceed the limit by one time. The weight difference limit of the dripping pills conforms to the appendix 11 pages of the second part of the 2000 th edition of Chinese pharmacopoeia.

And (3) content determination: precisely weighing the dripping pills, placing into a 25ml measuring flask, adding a small amount of anhydrous ethanol for dissolving, adding phosphate buffer solution with pH6.8 for constant volume, shaking up, and measuring the content of nervonic acid by gas chromatography, wherein the content of nervonic acid in three batches is 0.67%, 0.59% and 0.63%.

Dissolution rate: the dissolution rate is measured according to the method in the appendix of the second part of the Chinese pharmacopoeia 2015. The dissolution rates of the three batches were: 93.45% 92.33% 91.57%. Indicating good dissolution.

Comparative example 1

Preparation of drop pills of extract of Acer truncatum

The acer truncatum bunge extract prepared in example 1 was taken.

Preparing the medicine and the auxiliary materials: weighing 60g of Acer Truncatum Bunge extract, adding appropriate amount of anhydrous ethanol, dissolving with slight heat, adding 180g of PEG6000 and 20g of beta-cyclodextrin, and heating for melting. Adding into molten liquid (60 deg.C water bath for heat preservation), stirring, mixing, standing in 60 deg.C water bath for heat preservation for 30min until ethanol is completely volatilized (no alcohol smell), and removing bubbles to obtain medicine and adjuvants.

Transferring the uniformly mixed molten liquid of the medicines and the auxiliary materials into a liquid storage barrel of a dripping pill machine, controlling the dripping speed under the condition of keeping the temperature at 80-85 ℃, dripping the molten liquid into condensate drop by drop until the mixture is completely condensed, pouring out the condensate, collecting the dripping pills, draining, removing the condensate on the pills by using filter paper, placing the dripping pills in a silica gel dryer for 24 hours, weighing, and calculating the yield to obtain 9000 acer truncatum bunge extract dripping pills (30 mg/pill) (test article).

Comparative example 2

Preparation of polygala root extract drop pills

The polygala tenuifolia extract prepared in example 2 was taken.

Preparing the medicine and the auxiliary materials: weighing 60g of polygala tenuifolia extract, adding a proper amount of absolute ethyl alcohol, dissolving by slight heating, adding 180g of PEG6000 and 20g of beta-cyclodextrin, and heating and melting. Adding into molten liquid (60 deg.C water bath for heat preservation), stirring, mixing, standing in 60 deg.C water bath for heat preservation for 30min until ethanol is completely volatilized (no alcohol smell), and removing bubbles to obtain medicine and adjuvants.

And transferring the uniformly mixed molten liquid of the medicines and the auxiliary materials into a liquid storage barrel of a pill dropping machine, controlling the dropping speed under the condition of keeping the temperature at 80-85 ℃, dropping the molten liquid into condensate drop by drop until the mixture is completely condensed, pouring out the condensate, collecting the dropping pills, draining, removing the condensate on the pills by using filter paper, placing the pills in a silica gel dryer for 24 hours, weighing, and calculating the yield to obtain 9000 pills (tested products) of the polygala tenuifolia extract (30 mg/pill).

Drug testing

In order to compare the medical effects of the dropping pills (test products) of the patent, the single dropping pills of the acer truncatum bunge extract are prepared according to the preparation method of the test products. The content of nervonic acid is 0.63% by determination, which is equivalent to the nervonic acid content in the tested product.

In order to compare the medical effects of the dripping pills (test products) of the patent, the dripping pills (pure compounds) of nervonic acid are prepared according to the preparation method of the test products. The content of nervonic acid is 0.64% by determination, which is equivalent to the nervonic acid content in the tested product.

In order to compare the medical effects of the dripping pills (test products) of the patent, single polygala tenuifolia extract dripping pills are prepared according to the preparation method of the test products, and about 9000 pills are prepared from 60g of polygala tenuifolia extract.

Sleep improvement test

1. Animal(s) production

The KM animal mice, half of females, have the weight of 18-22 g, and are provided by the Chinese food and drug testing institute (animal license number: SCXK (Jing) 2014-0013). Feeding conditions are as follows: in a conventional animal room, animals can freely eat and drink pure water at room temperature of 22-25 ℃ and relative humidity of 50-60%.

2. Medicaments and their grouping

The experimental animals are adaptively fed for one week and are randomly divided into 6 groups, namely a blank (water) control group, a model drug (sodium pentobarbital) control group (distilled water), a nervonic acid dropping pill group (4g/kg), a test article high dose group (8g/kg), a test article medium dose group (4g/kg) and a test article low dose group (2g/kg) according to the body weight. Each group had 10 animals (male/female 5/5).

3. Experiment of

The dropping pills of each group are prepared into 200mg/ml (suspension) aqueous solution, after the oral administration for 30 minutes by mice, 50mg/kg of pentobarbital sodium is respectively injected into the abdominal cavity, and the time for prolonging the sleep of the mice of each group is observed. As in table 1.

TABLE 1 test article extended pentobarbital sodium sleep time results

P <0.05 compared to control, P <0.01 compared to control.

4. Conclusion

The high dose group in the test article significantly improved the sleep of the mice, specifically in prolonging the sleep time of the sodium pentobarbital. And the effect is obviously stronger than that of nervonic acid.

Test for improving Depression

Mouse tail suspension test.

1. Animal(s) production

The KM mouse is male and has the weight of 18-22 g. Wistar rats, male, weighing 180-. Provided by the Chinese food and drug testing institute (animal license number: SCXK (Jing) 2014-0013). Feeding conditions are as follows: in a conventional animal room, animals can freely eat and drink pure water at room temperature of 22-25 ℃ and relative humidity of 50-60%.

2. Medicaments and their grouping

The experimental animals are adaptively fed for one week and are randomly divided into a blank (water) control group, a model drug (sodium pentobarbital) control group (distilled water), a nervonic acid dropping pill group (4g/kg), a test product high dose (8g/kg) and a test product medium dose group (4g/kg) according to the body weight, and a desipramine 20mg/kg positive drug control is set.

3. Test of

Mouse tail suspension test

The mice are placed in cylindrical glass jars with the height of 20cm and the diameter of 10cm, one cylinder is used, the water depth in the jar is 10cm, the water temperature is 25 ℃, after the mice swim for 2 minutes, the observation is immediately carried out for 4 minutes, the mice stop struggling in the water within 4 minutes or are in a floating state, and only small limbs move to keep the head floating on the water surface for a continuous time (immobility time, seconds). The drug or distilled water was either gavaged or injected intraperitoneally 30 minutes before testing. The result shows that the test article has obvious depression improving effect at low and medium dosage. The effect is obviously better than that of the nervonic acid dripping pill group. The results are shown in Table 2.

TABLE 2 influence of the test substances on the immobility time of the tail suspension of mice

X ± SD, drugs were all administered 30 minutes prior to the trial: the desipramine is injected into the abdominal cavity, and other medicines are taken orally; comparison with the same batch of test solvent controls: p <0.05, P <0.01, P < 0.001.

B forced swimming test

The test article significantly shortens the immobility time during forced swimming; the medicine is not in the dosage range, and also shows better antidepressant effect, and the effect of the large-dosage group is close to that of the positive medicine and better than that of the nervonic acid dripping pill group (table 3).

TABLE 3 influence of test article on immobility time of forced swimming of mice

X ± SD, drugs were all administered 30 minutes prior to the trial: the desipramine is injected into the abdominal cavity, and the rest is taken orally; comparison with the same batch of test solvent controls: p <0.05, P < 0.01.

Forced swimming test for rats C

Rats were placed in glass jars of 20cm internal diameter and 40cm height, one in each jar, with a water depth of 24cm and a water temperature of 28-29 deg.C (water was used only once in each jar). On the first day of the experiment, each rat was pre-swim for 15 minutes, then was taken out under a light and wiped dry into a cage, and after 24 hours the experiment was performed, the rats were re-placed in the jar, observed for 5 minutes, and accumulated for 5 minutes until the rats stopped struggling in the water, or were in a floating state with only occasional limb movements to maintain the duration of head floating on the water (immobility time, seconds). To avoid the bias of observation, the observer observed the drug without any knowledge of the drug administration. Each rat was used for only 1 trial, with either drug or distilled water gavage or intraperitoneal injection 30 minutes before testing. The test result shows that the test article can obviously shorten the immobility time of forced swimming of strong rats and has better effect than the nervonic acid dripping pill group. Pharmacological data indicate that the medicine has good depression improving effect and results shown in table 4.

TABLE 4 influence of test substances on the immobility time of forced swimming rats

X ± SD, drugs were all administered 30 minutes prior to the trial: the desipramine is injected into the abdominal cavity, and the rest is taken orally; comparison with the same batch of test solvent controls: p <0.05, P <0.01, P < 0.001.

Claims (8)

1. A brain-strengthening and intelligence-improving composition comprising:

90-10 wt% of acer truncatum seed extract,

preferably 80 to 20 wt%, more preferably 60 to 40 wt%;

10-90 wt% of polygala root extract,

preferably 20-80 wt%, more preferably 40-60 wt%, based on the total mass of acer truncatum seed extract and polygala tenuifolia extract.

2. The composition as claimed in claim 1, wherein the acer truncatum buge seed extract is an extract obtained by extracting acer truncatum buge seeds with alcohol, ether, or saturated alkane.

3. The composition according to claim 1 or 2, wherein the polygala tenuifolia extract is an extract obtained by extracting polygala tenuifolia serving as a traditional Chinese medicine raw material with any one of alcohol, ether and saturated alkane.

4. The composition of claim 2, wherein acer truncatum seed extract is prepared by the steps of:

A) extracting Acer Truncatum Bunge seed with one of alcohol, ether and saturated alkane under heating;

B) recovering solvent under reduced pressure to obtain extract.

5. The composition according to claim 3, wherein the polygala tenuifolia extract is prepared by the steps of:

A) extracting Acer Truncatum Bunge seed with one of alcohol, ether and saturated alkane under heating;

B) recovering solvent under reduced pressure to obtain extract.

6. The composition of any one of claims 1-5, in the form of a drop pill.

7. The composition of claim 6, wherein the dropping pill is prepared by the steps of:

weighing Acer truncatum seed extract and cortex et radix Polygalae extract, adding appropriate amount of anhydrous ethanol, dissolving with slight heat, adding the dissolved solution into PEG6000-4000 molten liquid, stirring, mixing, standing in water bath, keeping the temperature for a period of time until the ethanol is completely volatilized, and removing bubbles to obtain medicine and adjuvants;

transferring the uniformly mixed molten liquid of the medicines and the auxiliary materials into a liquid storage barrel of a pill dropping machine, controlling the dropping speed under the condition of keeping the temperature at 80-85 ℃, dropping the molten liquid into the condensate drop by drop until the molten liquid is completely condensed, pouring off the condensate, collecting the dropping pills, draining, removing the condensate on the pills by using filter paper, and drying.

8. Use of a composition according to any one of claims 1-7 in the manufacture of a medicament for the treatment of depression and/or sleep disorders.

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