CN1097465C - Fatigue resisting composition - Google Patents

Abstract

The present invention provides a fatigue resisting composition mainly prepared from an extract product of folium ginkgo and tea polyphenols. The fatigue resisting composition comprises the components of the weight percentage: 30 to 50% of extract product of folium ginkgo, 20 to 40 % of tea polyphenols, 1 to 10 % of dry freezing powder of bee milk, and cornstarch as the rest. The present invention also provides the preparation method of the composition, mainly the preparation method of the extract product of the folium ginkgo. Compared with the previous effect that an extract product of folium ginkgo or tea polyphenols is singly used, the fatigue resisting composition provided by the present invention has an obvious enhancement effect. The preparation method of the present invention increases the content of flavone as an effective component in the extract product of the folium ginkgo.

Description

Anti-Fatigue Composition

The present invention relates to health care, field of medicaments, be specifically related to compound gingko leaf preparation.

Semen Ginkgo (Ginkgo biloba L) is the something lost plant in the most ancient middle living age, only deposits a section one and belongs to a kind ofly, has the title of gymnosperm " living fossil ".Though the earth in time immemorial through a series of great changes, fails Semen Ginkgo is become extinct as dinosaur all the time, scientists gives the credit to this existence miracle of Semen Ginkgo the vitality of it self tanacity.Our ancestors use it for very early and prevent and cure diseases and the health care aspect, effects such as according to Shennong's Herbal record, Semen Ginkgo has lung moistening, relievings asthma, refreshment.Really its research of carrying out the medicines and health protection aspect is started from the seventies, utilize Semen Ginkgo to make various preparations in the world, control cardiovascular and cerebrovascular disease and peripheral vessels dysfunction are obtained good curative effect.Think Folium Ginkgo at present except containing compositions such as alkaloid, trace element, aminoacid, its main active ingredient is Folium Ginkgo extract (GBE), i.e. flavone and terpene lactones chemical compound.

Tea polyphenols is the complex that separates the polyphenol compound of purifying from natural plants Folium Camelliae sinensis, and the biological activity of this compounds, health care also receive the very big concern of domestic and international medical circle.Its active component also is the tribute letones.

Yet, though the pharmacological action of lot of documents report Semen Ginkgo and tea polyphenols is arranged, there is not the people that compound preparation is made in they and Lac regis apis dry freeze powder, more the someone does not expect that this compound preparation drug effect can strengthen greatly.

The present inventor has found the synergistic enhancing effect of Folium Ginkgo, tea polyphenols and Lac regis apis dry freeze powder through concentrating on studies, thereby, an object of the present invention is to provide the anti-Fatigue Composition of mainly forming by Folium Ginkgo extract, tea polyphenols and Lac regis apis dry freeze powder.

Another object of the present invention provides the preparation method of anti-Fatigue Composition.

Anti-Fatigue Composition of the present invention comprises:

Folium Ginkgo extract 30-50 weight %

Tea polyphenols 20-40 weight %

Lac regis apis dry freeze powder 1-10 weight %

The corn starch surplus

The preparation method of anti-Fatigue Composition of the present invention comprises: extract Folium Ginkgo extract; Reach Folium Ginkgo extract, tea polyphenols, Lac regis apis dry freeze powder and corn starch in described ratio uniform mixing.

A preferred embodiment of the present invention provides the anti-Fatigue Composition with following ratio:

Folium Ginkgo extract 40-45 weight %

Tea polyphenols 30-35 weight %

Lac regis apis dry freeze powder 5-10 weight %

The corn starch surplus

Another preferred embodiment of the present invention provides the method that is prepared as follows Folium Ginkgo extract, comprises the steps:

(1) Folium Ginkgo 65% alcohol reflux is got filtrate, system extractum;

(2) extractum adds the ZTC clarifier, and precipitation is filtered;

(3) above-mentioned (2) gained filtrate is adsorbed through the macroporous resin bed, ethanol elution, and eluent concentrates, and drying gets total flavones;

(4) above-mentioned (2) gained precipitation ethyl acetate extraction filters, and obtains total lactone through column chromatography;

(5) merge above-mentioned (3) gained total flavones and the total lactone of (4) gained, obtain Folium Ginkgo extract.

Fig. 1 is a Folium Ginkgo extract preparation technology flow chart.

Anti-Fatigue Composition of the present invention can be made into various dosage forms, as dosage forms such as gastric solubleness or enteric coated capsule, tablet, pill, powder, dissolved granule, oral liquids.As required, in preparation, can add various pharmaceutical carriers, as excipient, lubricant, disintegrating agent, antioxidant etc.

Anti-Fatigue Composition provided by the invention is compared with the effect of Folium Ginkgo extract or tea polyphenols with single in the past, has tangible enhancement effect.And anti-Fatigue Composition of the present invention does not have any toxicity, and animal is taken for a long time and do not see mutagenesis and teratogenesis.Therefore, anti-Fatigue Composition of the present invention is safely and effectively, is suitable for that work rhythm is fast, brain overwork and fatiguability crowd take for a long time.

In the preparation method provided by the invention, the preparation technology of Folium Ginkgo extract has adopted the ZTC clarifier to carry out sedimentation, the pH3-4 cleaning mixture adsorbs and spray drying technology, reach up-to-standard, stable Folium Ginkgo extract, its pyrite and lactone content reach respectively more than 26% and 6%, be higher than adopt that water precipitating falls, the common process of the absorption of neutral cleaning mixture and drying under reduced pressure.

Below with embodiment and experimental example the present invention is illustrated, they are intended to set forth optimum implementation of the present invention.Those skilled in the art are according to enlightenment of the present invention, and the various changes in conjunction with the general knowledge of this area is done all drop in the scope of the application's claim.

By the elaboration of these embodiment and experimental example, it is more clear that above-mentioned purpose of the present invention and effect also will become.

The preparation of embodiment 1 Folium Ginkgo extract

(1) with 5.0 kg silver Folium Pruni with 65% alcohol reflux 4.5 hours, filter, filtrate decompression (4.0kPa) concentrates, the extractum that obtains adds water and ZTC clarifier (2% volume), places 8.0 hours after-filtration.

(2) filtrate of gained in the step (1) is gone up the macroporous resin bed and adsorb, water and 25% ethanol wash the back successively and use 70% ethanol elution, and cleaning mixture and eluant all are adjusted to pH3.Eluent concentrating under reduced pressure, the concentrated solution of gained carry out spray drying (200 ℃ of inlet temperatures, 80 ℃ of outlet temperatures), obtain total flavones 1300g.

(3) with the residue of gained in the step (1) with ethyl acetate extraction, filter, carry out column chromatography, obtain total lactone 300g.

(4) total lactone and total flavones are merged, i.e. Folium Ginkgo extract.

Embodiment 2-3

Spray-dired temperature is respectively 80 ℃ of 370 ℃ of the imports, outlet 90 ℃ and 180 ℃ of imports, outlet in step (3), and operation obtains Folium Ginkgo extract similarly to Example 1.

Comparative example 1

Do not add the clarifier in step (1), operation obtains Folium Ginkgo extract similarly to Example 1.

Comparative example 2,3

Except pH in the step (2) be adjusted to respectively 7 and 5-7, operation obtains Folium Ginkgo extract similarly to Example 1.

Comparative example 4,5

Except adopting the normal pressure oven dry (to be respectively 80 ℃, 4 hours in the step (3); 70 ℃, 7 hours) in addition, operation obtains Folium Ginkgo extract similarly to Example 1.

Comparative example 6

Except adopting vacuum drying (60 ℃, 2 hours) in the step (3), operation obtains Folium Ginkgo extract similarly to Example 1.Effect comparison (1) water precipitating of extraction Folium Ginkgo extract adds the influence of ZTC to flavones content in the product in falling under experimental example 1 different condition

Table 1

	Condition	The flavones content of product (%)
			Embodiment 1 comparative example 1	Add ZTC and do not add ZTC	27.5 22.3

(2) acid absorption and neutral absorption are to the influence of flavones content in the product

Table 2

	Adsorption liquid pH	The flavones content of product (%)
			Comparative example 2 comparative examples 3 embodiment 1	7 5-7 3-4	20.4 23.9 27.6

(3) drying means is to the influence of flavones content in the product

Table 3

	Drying means	The flavones content of product (%)
			Comparative example 4 comparative examples 5 comparative examples 6 embodiment 1 embodiment 2 embodiment 3	(80 ℃ of room temperature oven dry, 4 hours) (70 ℃ of room temperature oven dry, 7 hours) (60 ℃ of vacuum dryings, 2 hours) spray drying (200 ℃ of imports, export 80 ℃) spray drying (370 ℃ of imports, export 90 ℃) spray drying (180 ℃ of imports, export 800 ℃)	12.7 16.4 24 27.5 26.4 27.1

From above result as seen, the improvement of the inventive method has improved the content of effective ingredient flavone in the Folium Ginkgo extract.

Embodiment 4

In following ratio each composition is fully mixed, makes compositions of the present invention:

Folium Ginkgo extract 30-50 weight %

Tea polyphenols 20-40 weight %

Lac regis apis dry freeze powder 1-10 weight %

The corn starch surplus

Embodiment 5 capsular preparations

With the compositions vacuum drying of embodiment 4 gained sterilization (80 ℃ of temperature, time 6-8 hour, pressure 6kPa) back capsule charge, 300 milligrams of every charging quantities.

Embodiment 6

Be mixed with compositions as following weight percent:

Table 4

	Prescription 1	Prescription 2	Prescription 3	Prescription 4	Prescription 5	Prescription 6	Prescription 7
								Folium Ginkgo extract tea polyphenols Lac regis apis dry freeze powder corn starch	35 25 2 38	40 30 5 25	45 35 10 10	50 40 10 0	100 - - -	- 100 - -	- - 100 -

Experimental example 2 anti-fatigue tests

Each compound composition is mixed with suspension with 2% cmc soln.

Selecting body weight for use is 70 of the male Wistar rats of 150 ± 7.5g, is divided into 7 groups, 10 every group, freely ingest and drink water, test group gavages each compound composition when early morning (once a day, gavage) through stomach tube respectively, dosage is the 1g/kg body weight, and matched group gavages the equal-volume cmc soln.The continuous irrigation harmonization of the stomach raised for 3 weeks.Irritate the last time behind the stomach and to carry out swimming test and pole-jump test half an hour according to a conventional method.The results are shown in Table 5.

Table 5 is respectively filled a prescription the resisting fatigue effect relatively

Prescription	Number of animals	The rats'swimming time (second)	The rat pole-climbing time (second)
				1234567 control groups	10 10 10 10 10 10 10 10	42.7±3.1*# 67.6±4.9*△☆# 56.8±4.7*△☆# 52.7±3.9*△ 44.9±3.6* 49.2±5.1* 48.6±4.7* 36.3±4.7	32.6±5.7* 21.7±7.2*△☆# 24.5±6.6*△☆# 28.4±5.3* 32.1±6.2* 34.1±5.9* 34.6±5.2* 42.2±7.2

Annotate: * represents to compare with the blank group, difference significance (P＜0.05).

△ represents to compare difference significance (P＜0.05) for 5 groups with prescription.

☆ represents to compare difference significance (P＜0.05) for 6 groups with prescription.

# represents to compare difference significance (P＜0.05) for 7 groups with prescription.

As can be seen from the above results, prescription of the present invention all has antifatigue effect, and 2 and 3 effect is the best to fill a prescription.Simultaneously also as can be seen, it is single with Folium Ginkgo extract and single the effective of tea polyphenols of using to take anti-Fatigue Composition ratio of the present invention, promptly has obvious synergistic effect.

Experimental example 3 acute toxicity tests

100 of Kunming mouses (body weight 18-22 gram), 20 of SD rats (body weight 180-220 gram), female half and half, grouping, gavage the present composition with following dosage respectively: mice dosage group is 2g/kg, 4g/kg, 6g/kg, 8g/kg and 10g/kg; Rat dosage group is 1g/kg, 2.15g/kg, 4.64g/kg and 10g/kg.Observed for 2 weeks after irritating stomach, rat and mice there is no abnormal response, activity freely, none death.

Above result shows, the LD of rat and mice ₅₀Value is all greater than 10k/kg.

Experimental example 4 chronic toxicity tests

With 80 of SD rats, be divided into 4 groups, 20 every group, male and female half and half, test group dosage is respectively 0.10g/kg, 0.75g/kg and 1.5g/kg, mixes feedstuff, and matched group is the normal feedstuff group.Observe after 30 days and put to death, do postmortem.

The result: animal activity freely, hair luster, feed, defecation are normal.All there is not significant difference at aspects such as body weight gain, physiochemical indice, biochemical measurement indexs between each group.The postmortem result does not see the pathological change that there were significant differences.

Experimental example 5 mutagenesis and tertogenicity test

Kunming mouse (25-28 gram), test group dosage is respectively 1.25g/kg, 2.5g/kg and 5.0g/kg in the mutagenicity test, and test group dosage is respectively 2.5g/kg, 5.0g/kg and 7.5g/kg in the tertogenicity test.All with the negative matched group of distilled water, the positive matched group of cyclophosphamide 40mg/kg.Make bone marrow nuclear test and testicular chromosome aberration test respectively by " foodsafety poison lithium is learned assessment process and method ".

The result: each test group micronuclear rates and negative control group do not have significant difference (p＞0.05), and the positive controls micronuclear rates is significantly higher than each test group and negative control group (p＜0.01).

Each test group chromosome aberrations rate and negative control group do not have significant difference (p＞0.05), and positive controls is significantly higher than each test group and negative control group (p＜0.01).

Claims (5)

1. anti-Fatigue Composition comprises:

Folium Ginkgo extract 30-50 weight %

Tea polyphenols 20-40 weight %

Lac regis apis dry freeze powder 1-10 weight %

The corn starch surplus

2. anti-Fatigue Composition as claimed in claim 1 wherein comprises:

Folium Ginkgo extract 40-45 weight %

Tea polyphenols 30-35 weight %

Lac regis apis dry freeze powder 5-10 weight %

The corn starch surplus

3. anti-Fatigue Composition as claimed in claim 1, the dosage form of described compositions are capsule.

4. the preparation method of anti-Fatigue Composition as claimed in claim 1 or 2 comprises: extract Folium Ginkgo extract; Reach Folium Ginkgo extract, tea polyphenols, Lac regis apis dry freeze powder and corn starch by described mixed.

5. preparation method as claimed in claim 4, wherein the preparation of Folium Ginkgo extract comprises the steps:

(1) Folium Ginkgo 65% alcohol reflux is got filtrate, system extractum;

(2) extractum adds the ZTC clarifier, and precipitation is filtered;

(3) above-mentioned (2) gained filtrate is adsorbed through the macroporous resin bed, ethanol elution, and eluent concentrates, and drying gets total flavones;

(4) above-mentioned (2) gained precipitation ethyl acetate extraction filters, and obtains total lactone through column chromatography;

(5) merge above-mentioned (3) gained total flavones and the total lactone of (4) gained, obtain Folium Ginkgo extract.