阅读说明：本技术 一种杜仲提取物组合物及其制备方法和应用 (Eucommia ulmoides extract composition and preparation method and application thereof ) 是由 陈梁 李小锋 刘厚权 毛金娣 林飞英 张梅红 胡吉忠 夏淑英 于 2021-07-07 设计创作，主要内容包括：本发明属于药物制备技术领域,具体涉及一种杜仲提取物组合物及其制备方法和应用。所述组合物包括以下组分：京尼平苷酸、绿原酸、桃叶珊瑚苷、松脂醇二葡萄糖苷和脱氢二松柏醇二葡萄糖苷的混合物。该提取物组合物能够有效治疗原发性高血压或肾虚证,并且无毒副作用,用量少,可以有效降低用药成本。(The invention belongs to the technical field of medicine preparation, and particularly relates to an eucommia ulmoides extract composition and a preparation method and application thereof. The composition comprises the following components: a mixture of geniposide, chlorogenic acid, aucubin, pinoresinol diglucoside and dehydrodiconiferyl alcohol diglucoside. The extract composition can effectively treat primary hypertension or kidney deficiency, has no toxic or side effect and low dosage, and can effectively reduce the medication cost.)

1. An eucommia ulmoides extract composition comprises the following components:

a mixture of geniposide, chlorogenic acid, aucubin, pinoresinol diglucoside and dehydrodiconiferyl alcohol diglucoside.

2. The eucommia ulmoides extract composition of claim 1, comprising the following components in parts by weight: 1-15 parts of geniposide, 1-10 parts of chlorogenic acid, 5-15 parts of aucubin, and 1-10 parts of a mixture of pinoresinol diglucoside and dehydrodiconiferyl alcohol diglucoside.

3. The eucommia ulmoides extract composition of claim 1, comprising the following components in parts by weight: 5-8 parts of geniposide, 3-6 parts of chlorogenic acid, 6-8 parts of aucubin, and 3-7 parts of a mixture of pinoresinol diglucoside and dehydrodiconiferyl alcohol diglucoside.

4. A method for preparing an eucommia ulmoides extract composition as set forth in any one of claims 1 to 3, comprising the steps of:

(1) pulverizing Eucommiae cortex, adding distilled water, adding solubilizer, extracting, and filtering to obtain water extractive solution and residue;

(2) adding the filter residue into ethanol water solution, extracting, and filtering to obtain ethanol extract;

(3) adsorbing the water extract with HZ-820 macroporous resin, eluting with distilled water to remove impurities to obtain distilled water eluate A; eluting with ethanol water solution to obtain aucubin;

(4) mixing the remaining water extract after adsorption by HZ-820 type macroporous resin with distilled water eluent A, adjusting pH to 3-4, adsorbing with XAD-6 type macroporous resin, eluting with distilled water to remove impurities, and making into distilled water eluent B for use;

eluting with 5-10% ethanol water solution, collecting eluate, and making geniposide;

eluting with 15-20% ethanol water solution, collecting eluate, adsorbing the eluate with NKA-2, and eluting with 10-15% ethanol water solution to obtain chlorogenic acid;

(5) mixing the water extractive solution adsorbed by XAD-6 macroporous adsorbent resin with distilled water eluent B, adjusting pH to 10-12, adsorbing with D101 type resin, eluting with ethanol water solution to obtain mixture of pinoresinol diglucoside and dehydroconiferyl diglucoside;

(6) mixing the prepared mixture of geniposide, chlorogenic acid, aucubin, pinoresinol diglucoside and dehydro-dibastinol diglucoside according to a ratio to obtain the eucommia ulmoides extract composition.

5. The method for preparing the eucommia ulmoides extract composition according to claim 4, wherein the amount of the distilled water added in the step (1) is 5 to 8 times the mass of the eucommia ulmoides; the extraction temperature is 60-80 deg.C for 30-60min, and boiling for 1-2 hr.

6. The method for preparing the eucommia ulmoides extract composition according to claim 4, wherein the solubilizer is sodium acetate and polysorbate 80 in step (1); the mass ratio of sodium acetate to polysorbate 80 in the solubilizer is 1-3: 1; the usage amount of the solubilizer is 1-2% of the mass of the eucommia ulmoides.

7. The method for preparing the eucommia ulmoides extract composition according to claim 4, wherein in the step (2), the mass fraction of the ethanol aqueous solution is 45 to 75%; the dosage of the ethanol water solution is 3-5 times of the mass of the filter residue; the extraction time is 1-2 h.

8. The method for preparing the eucommia ulmoides extract composition according to claim 4, wherein in the step (3), the mass fraction of the ethanol aqueous solution is 30-45%; the dosage of the ethanol water solution is 3-5 BV; the elution rate is 2-3 BV/h; the using amount of the distilled water is 2-3 BV; the elution rate is 1-4 BV/h;

in the step (4), the using amount of the distilled water is 1-2 BV; the elution rate is 2-3 BV/h; the pH value is adjusted by using citric acid; the using amount of the ethanol water solution with the mass fraction of 5-10% is 1-3 BV; the elution rate is 1-3 BV/h; the usage amount of the ethanol water solution with the mass fraction of 15-20% is 3-6 BV; the elution rate is 1-2 BV/h; the dosage of the 10-15% ethanol water solution is 1-3 BV; the elution rate is 1-3 BV/h.

9. The method for preparing the eucommia ulmoides extract composition according to claim 4, wherein the agent for adjusting the pH in the step (5) is sodium hydroxide; in the step (5), the mass concentration of the ethanol water solution is 10-30%, and the using amount is 3-5 BV; the elution rate is 1-3 BV/h.

10. Use of an eucommia ulmoides extract according to any one of claims 1 to 3 or an eucommia ulmoides extract composition according to any one of claims 4 to 9 for the preparation of a medicament for treating essential hypertension or kidney deficiency.

Technical Field

The invention belongs to the technical field of medicine preparation, and particularly relates to an eucommia ulmoides extract composition and a preparation method and application thereof.

Background

Hypertension is a clinical syndrome characterized by an increase in systemic arterial blood pressure (systolic pressure and/or diastolic pressure) (systolic pressure not less than 140 mm Hg, diastolic pressure not less than 90 mm Hg), which may be accompanied by functional or organic lesions in organs such as heart, brain, kidney, etc. The failure to find the exact cause of the increase in blood pressure is called essential hypertension.

In the prior art, there are methods for treating essential hypertension, for example, chinese patent application CN103127421A discloses a traditional Chinese medicine composition for treating essential hypertension, which is prepared from prunella vulgaris, chrysanthemum, cassia seed, buddleja officinalis, apocynum venetum, coix seed, motherwort, suberect spatholobus stem, Chinese yam and eucommia bark.

Chinese patent application CN102526470A discloses a pharmaceutical composition for treating essential hypertension, which is prepared from the following active ingredients in parts by weight: 10-15 parts of chrysanthemum, 10-15 parts of mulberry leaf, 12-16 parts of earthworm, 12-16 parts of scutellaria baicalensis, 12-16 parts of radix scrophulariae, 18-22 parts of salvia miltiorrhiza, 12-16 parts of radix rehmanniae, 10-15 parts of radix paeoniae alba, 8-12 parts of radix ophiopogonis, 18-22 parts of radix angelicae pubescentis and 12-16 parts of herba cirsii jeponici.

Such as Chinese patent application CN102319381A chrysanthemum 9-15 parts, gastrodia elata 8-12 parts, cassia occidentalis 10-20 parts, glabrous greenbrier rhizome 25-35 parts, poria peel 15-25 parts, cortex mori 12-18 parts, Chinese waxgourd peel 15-25 parts, semen plantaginis 15-25 parts, alisma orientale 12-18 parts, raw oyster 15-25 parts, tribulus terrestris 10-15 parts, pipewort 8-12 parts, butterflybush flower 8-12 parts, stiff silkworm 12-18 parts and poria 15-25 parts.

Chinese patent application CN101822789A discloses a hypotensor for treating essential hypertension, which is prepared from the following raw materials in parts by weight: 10-20g of gastrodia elata; 10-20g of cape jasmine; 15-25ml of bamboo juice; 25-35g of decocted abalone shell; 25-35g of decocted nacre; 10-20g of uncaria; 10-15g of eucommia ulmoides; 10-20g of loranthus parasiticus; 10-15g of scutellaria; 6-12g of red peony root; 15-25g of keel; 15-25g of oysters; 15-25g of polyporus umbellatus; 15-25g of poria with hostwood; 4-8g of liquorice; 10-20g of bamboo shavings; 10-15g of poria cocos; 6-10g of radix et rhizoma Rhei; 6-10g of safflower; 10-15g of cassia occidentalis, and the traditional Chinese medicine can tonify qi, activate blood, soften blood vessels, soothe heart and activate pulse, has the effects of replenishing kidney energy, improving cardiac power, expanding and softening blood vessels and the like, effectively eliminates headache, insomnia and palpitation, thoroughly cures hypertension and avoids relapse.

Although all the drugs have certain effect of treating the primary hypertension, the above technologies have various drug types and complex preparation methods, and cannot eliminate the influence of other impurities, and on the other hand, the utilization rate of active ingredients may be influenced, and the pharmaceutical cost is increased.

Disclosure of Invention

In order to overcome the technical problems, the invention provides an eucommia ulmoides extract composition and a preparation method and application thereof. The extract composition can effectively treat primary hypertension or kidney deficiency, has no toxic or side effect and low dosage, and can effectively reduce the medication cost.

In order to achieve the above purpose, the technical scheme provided by the invention is as follows:

a composition of eucommia ulmoides extract comprises the following components:

a mixture of geniposide, chlorogenic acid, aucubin, pinoresinol diglucoside and dehydrodiconiferyl alcohol diglucoside.

Preferably, the eucommia ulmoides extract composition comprises the following components in parts by weight:

1-15 parts of geniposide, 1-10 parts of chlorogenic acid, 5-15 parts of aucubin, and 1-10 parts of a mixture of pinoresinol diglucoside and dehydrodiconiferyl alcohol diglucoside.

Preferably, the eucommia ulmoides extract composition comprises the following components in parts by weight:

5-8 parts of geniposide, 3-6 parts of chlorogenic acid, 6-8 parts of aucubin, and 3-7 parts of a mixture of pinoresinol diglucoside and dehydrodiconiferyl alcohol diglucoside.

Another object of the present invention is to provide a method for preparing the eucommia ulmoides extract composition, comprising the steps of:

(1) pulverizing Eucommiae cortex, adding distilled water, adding solubilizer, extracting, and filtering to obtain water extractive solution and residue;

(2) adding the filter residue into ethanol water solution, extracting, and filtering to obtain ethanol extract;

(3) adsorbing the water extract with HZ-820 macroporous resin, eluting with distilled water to remove impurities to obtain distilled water eluate A; eluting with ethanol water solution to obtain aucubin;

(4) mixing the remaining water extract after adsorption by HZ-820 type macroporous resin with distilled water eluent A, adjusting pH to 3-4, adsorbing with XAD-6 type macroporous resin, eluting with distilled water to remove impurities, and making into distilled water eluent B for use;

eluting with 5-10% ethanol water solution, collecting eluate, and making geniposide;

eluting with 15-20% ethanol water solution, collecting eluate, adsorbing the eluate with NKA-2, and eluting with 10-15% ethanol water solution to obtain chlorogenic acid;

(5) mixing the water extractive solution adsorbed by XAD-6 macroporous adsorbent resin with distilled water eluent B, adjusting pH to 10-12, adsorbing with D101 type resin, eluting with ethanol water solution to obtain mixture of pinoresinol diglucoside and dehydroconiferyl diglucoside;

(6) mixing the prepared mixture of geniposide, chlorogenic acid, aucubin, pinoresinol diglucoside and dehydro-dibastinol diglucoside according to a ratio to obtain the eucommia ulmoides extract composition.

Preferably, in the step (1), the adding amount of the distilled water is 5-8 times of the mass of the eucommia ulmoides; the extraction temperature is 60-80 deg.C for 30-60min, and boiling for 1-2 hr.

Preferably, in step (1), the solubilizer is sodium acetate and polysorbate 80.

Preferably, in the step (1), the mass ratio of sodium acetate to polysorbate 80 in the solubilizer is 1-3: 1.

Preferably, the usage amount of the solubilizer is 1-2% of the mass of the eucommia ulmoides.

Preferably, in the step (2), the mass fraction of the ethanol aqueous solution is 45-75%.

Preferably, in the step (2), the dosage of the ethanol water solution is 3-5 times of the mass of the filter residue.

Preferably, in the step (2), the extraction time is 1-2 h.

Preferably, in the step (3), the mass fraction of the ethanol aqueous solution is 30-45%.

Preferably, in the step (3), the dosage of the ethanol water solution is 3-5 BV; the elution rate is 2-3 BV/h.

Preferably, in the step (3), the amount of the distilled water is 2-3 BV; the elution rate is 1-4 BV/h.

Preferably, in the step (4), the amount of the distilled water is 1-2 BV; the elution rate is 2-3 BV/h.

Preferably, in step (4), the pH is adjusted using citric acid.

Preferably, in the step (4), the 5-10% mass fraction ethanol aqueous solution is used in an amount of 1-3 BV; the elution rate is 1-3 BV/h.

Preferably, in the step (4), the 15-20% mass fraction ethanol aqueous solution is used in an amount of 3-6 BV; the elution rate is 1-2 BV/h.

Preferably, in the step (4), the 10-15% mass fraction ethanol aqueous solution is used in an amount of 1-3 BV; the elution rate is 1-3 BV/h.

Preferably, in the step (5), the reagent for adjusting the pH value is sodium hydroxide.

Preferably, in the step (5), the mass concentration of the ethanol aqueous solution is 10-30%, and the using amount is 3-5 BV; the elution rate is 1-3 BV/h.

The invention also aims to provide application of the eucommia ulmoides extract in preparing a medicine for treating primary hypertension or kidney deficiency.

Compared with the prior art, the invention has the technical advantages that:

(1) the eucommia ulmoides extract composition provided by the invention can be used for treating primary hypertension or kidney deficiency.

(2) The mixture of sodium acetate and polysorbate 80 is used as a solubilizer, so that the extraction of effective components in eucommia ulmoides can be effectively promoted, and the utilization rate of the medicament is improved.

(3) The citric acid is used for adjusting the pH value of the water extract, so that the pH value of the citric acid can be effectively adjusted, and the drug effect of the extracted effective components can be effectively promoted.

Detailed Description

The present invention will be described below with reference to specific examples to make the technical aspects of the present invention easier to understand and grasp, but the present invention is not limited thereto. The experimental methods described in the following examples are all conventional methods unless otherwise specified; the reagents and materials are commercially available, unless otherwise specified.

Example 1

The composition of the eucommia ulmoides extract comprises the following components in parts by weight: 5 parts of geniposidic acid, 3 parts of chlorogenic acid, 6 parts of aucubin, and 3 parts of a mixture of pinoresinol diglucoside and dehydrodiconiferyl diglucoside.

The preparation method of the eucommia ulmoides extract composition comprises the following steps:

(1) pulverizing Eucommiae cortex, adding 6 times of distilled water, adding 1.5 wt% of sodium acetate and polysorbate 80 at a mass ratio of 2:1, extracting at 70 deg.C for 50min, boiling for 1.5 hr, and filtering to obtain water extractive solution and residue;

(2) adding the filter residue into 55 wt% ethanol water solution of 4 times, extracting for 1.5h, and filtering to obtain ethanol extract;

(3) adsorbing the water extract with HZ-820 type macroporous resin, eluting with 2.5BV distilled water at an elution rate of 2BV/h to remove impurities, and eluting with distilled water A; eluting with 35% ethanol water solution of 4BV at an elution rate of 2.5BV/h to obtain aucubin;

(4) mixing the residual water extract after adsorption by HZ-820 type macroporous resin with distilled water eluent A, adjusting pH to 3 with citric acid, adsorbing with XAD-6 type macroporous resin, eluting with 1BV distilled water for removing impurities at an elution rate of 2.5BV/h to obtain distilled water eluent B for later use;

eluting with 3BV of 6% ethanol water solution at an elution rate of 3BV/h, and collecting the eluate to obtain geniposide;

eluting with 4BV of 17% ethanol aqueous solution with elution rate of 1.5BV/h, collecting eluate, adsorbing the eluate with NKA-2, eluting with 2BV of 12% ethanol aqueous solution with elution rate of 2BV/h to obtain chlorogenic acid;

(5) mixing the water extract adsorbed by XAD-6 macroporous adsorption resin with distilled water eluent B, adjusting pH to 10 with sodium hydroxide, adsorbing with D101 type resin, eluting with 4BV aqueous solution of 20% ethanol at 2BV/h to obtain mixture of pinoresinol diglucoside and dehydrodiconiferyl alcohol diglucoside;

(6) mixing the prepared mixture of geniposide, chlorogenic acid, aucubin, pinoresinol diglucoside and dehydro-dibastinol diglucoside according to a ratio to obtain the eucommia ulmoides extract composition.

Example 2

The composition of the eucommia ulmoides extract comprises the following components in parts by weight: 8 parts of geniposidic acid, 6 parts of chlorogenic acid, 8 parts of aucubin, and 7 parts of a mixture of pinoresinol diglucoside and dehydrodiconiferyl diglucoside.

The preparation method of the eucommia ulmoides extract composition comprises the following steps:

(1) pulverizing Eucommiae cortex, adding 5 times of distilled water, adding 1 wt% of sodium acetate and polysorbate 80 at a mass ratio of 1:1, extracting at 80 deg.C for 30min, boiling for extracting for 1 hr, and filtering to obtain water extractive solution and residue;

(2) adding the filter residue into 5 times of 45 wt% ethanol water solution, extracting for 1h, and filtering to obtain an alcohol extract;

(3) adsorbing the water extract with HZ-820 type macroporous resin, eluting with 3BV distilled water at an elution rate of 1BV/h to remove impurities, and eluting with distilled water A; eluting with 30% ethanol water solution of 3BV at an elution rate of 2BV/h to obtain aucubin;

(4) mixing the residual water extract after adsorption of HZ-820 type macroporous resin with distilled water eluent A, adjusting pH to 4 with citric acid, adsorbing with XAD-6 type macroporous resin, eluting with 1BV distilled water for removing impurities at an elution rate of 2BV/h to obtain distilled water eluent B for later use;

eluting with 1BV of 5% ethanol water solution at an elution rate of 1BV/h, and collecting the eluate to obtain geniposide;

eluting with 3BV of 15% ethanol aqueous solution at an elution rate of 1BV/h, collecting the eluate, adsorbing the eluate with NKA-2, eluting with 1BV of 10% ethanol aqueous solution at an elution rate of 1BV/h to obtain chlorogenic acid;

(5) mixing the water extract adsorbed by XAD-6 macroporous adsorption resin with distilled water eluent B, adjusting pH to 12 with sodium hydroxide, adsorbing with D101 type resin, eluting with 10% ethanol water solution with 3BV mass concentration at an elution rate of 1BV/h, and making into mixture of pinoresinol diglucoside and dehydrodiconiferyl alcohol diglucoside;

(6) mixing the prepared mixture of geniposide, chlorogenic acid, aucubin, pinoresinol diglucoside and dehydro-dibastinol diglucoside according to a ratio to obtain the eucommia ulmoides extract composition.

Example 3

The composition of the eucommia ulmoides extract comprises the following components in parts by weight: 1 part of geniposidic acid, 1 part of chlorogenic acid, 5 parts of aucubin, and 1 part of mixture of pinoresinol diglucoside and dehydrodiconiferyl diglucoside.

The preparation method of the eucommia ulmoides extract composition comprises the following steps:

(1) pulverizing Eucommiae cortex, adding 8 times of distilled water, adding 2 wt% of sodium acetate and polysorbate 80 at a mass ratio of 3:1, extracting at 60 deg.C for 60min, boiling for extraction for 2 hr, and filtering to obtain water extractive solution and residue;

(2) adding the filter residue into 5 times of 75 wt% ethanol water solution, extracting for 2h, and filtering to obtain ethanol extract;

(3) adsorbing the water extract with HZ-820 type macroporous resin, eluting with 2BV distilled water at an elution rate of 4BV/h to remove impurities, and eluting with distilled water A; eluting with 45% ethanol water solution with 3BV mass fraction at 3BV/h to obtain aucubin;

(4) mixing the residual water extract after adsorption of HZ-820 type macroporous resin with distilled water eluent A, adjusting pH to 3 with citric acid, adsorbing with XAD-6 type macroporous resin, eluting with 2BV distilled water for removing impurities at an elution rate of 3BV/h to obtain distilled water eluent B for later use;

eluting with 3BV 10% ethanol water solution at 3BV/h, collecting eluate, and making geniposide;

eluting with 6BV of 20% ethanol aqueous solution at an elution rate of 2BV/h, collecting the eluate, adsorbing the eluate with NKA-2, eluting with 3BV of 15% ethanol aqueous solution at an elution rate of 3BV/h to obtain chlorogenic acid;

(5) mixing the water extract adsorbed by XAD-6 macroporous adsorption resin with distilled water eluent B, adjusting pH to 10 with sodium hydroxide, adsorbing with D101 type resin, eluting with 5BV ethanol water solution with mass concentration of 30%, with elution rate of 3BV/h, to obtain mixture of pinoresinol diglucoside and dehydrodiconiferyl alcohol diglucoside;

(6) mixing the prepared mixture of geniposide, chlorogenic acid, aucubin, pinoresinol diglucoside and dehydro-dibastinol diglucoside according to a ratio to obtain the eucommia ulmoides extract composition.

Example 4

The composition of the eucommia ulmoides extract comprises the following components in parts by weight: 15 parts of geniposidic acid, 10 parts of chlorogenic acid, 15 parts of aucubin, and 10 parts of a mixture of pinoresinol diglucoside and dehydrodiconiferyl diglucoside.

The preparation method of the eucommia ulmoides extract composition comprises the following steps:

(1) pulverizing Eucommiae cortex, adding 6 times of distilled water, adding 1.5 wt% of sodium acetate and polysorbate 80 at a mass ratio of 2:1, extracting at 70 deg.C for 50min, boiling for 1.5 hr, and filtering to obtain water extractive solution and residue;

(2) adding the filter residue into 55 wt% ethanol water solution of 4 times, extracting for 1.5h, and filtering to obtain ethanol extract;

(3) adsorbing the water extract with HZ-820 type macroporous resin, eluting with 2.5BV distilled water at an elution rate of 2BV/h to remove impurities, and eluting with distilled water A; eluting with 35% ethanol water solution of 4BV at an elution rate of 2.5BV/h to obtain aucubin;

(4) mixing the residual water extract after adsorption by HZ-820 type macroporous resin with distilled water eluent A, adjusting pH to 3 with citric acid, adsorbing with XAD-6 type macroporous resin, eluting with 1BV distilled water for removing impurities at an elution rate of 2.5BV/h to obtain distilled water eluent B for later use;

eluting with 3BV of 6% ethanol water solution at an elution rate of 3BV/h, and collecting the eluate to obtain geniposide;

eluting with 4BV of 17% ethanol aqueous solution with elution rate of 1.5BV/h, collecting eluate, adsorbing the eluate with NKA-2, eluting with 2BV of 12% ethanol aqueous solution with elution rate of 2BV/h to obtain chlorogenic acid;

(5) mixing the water extract adsorbed by XAD-6 macroporous adsorption resin with distilled water eluent B, adjusting pH to 10 with sodium hydroxide, adsorbing with D101 type resin, eluting with 4BV aqueous solution of 20% ethanol at 2BV/h to obtain mixture of pinoresinol diglucoside and dehydrodiconiferyl alcohol diglucoside;

(6) mixing the prepared mixture of geniposide, chlorogenic acid, aucubin, pinoresinol diglucoside and dehydro-dibastinol diglucoside according to a ratio to obtain the eucommia ulmoides extract composition.

Comparative example 1

The only difference compared to example 1 was the substitution of geniposide for chlorogenic acid.

The composition of the eucommia ulmoides extract comprises the following components in parts by weight: 8 parts of geniposide, 6 parts of aucubin, and 3 parts of a mixture of pinoresinol diglucoside and dehydrodiconiferyl alcohol diglucoside.

The preparation method of the eucommia ulmoides extract composition comprises the following steps:

(1) step (3), the same operation as in example 1;

(4) mixing the residual water extract after adsorption by HZ-820 type macroporous resin with distilled water eluent A, adjusting pH to 3 with citric acid, adsorbing with XAD-6 type macroporous resin, eluting with 1BV distilled water for removing impurities at an elution rate of 2.5BV/h to obtain distilled water eluent B for later use;

eluting with 3BV of 6% ethanol water solution at an elution rate of 3BV/h, and collecting the eluate to obtain geniposide;

(5) step (2), the operation is the same as example 1;

(6) and mixing the prepared mixture of geniposide, aucubin, pinoresinol diglucoside and dehydro-dibastinol diglucoside according to a ratio to obtain the eucommia ulmoides extract composition.

Comparative example 2

The only difference from example 1 is the replacement of geniposidic acid with chlorogenic acid.

The composition of the eucommia ulmoides extract comprises the following components in parts by weight:

8 parts of chlorogenic acid, 6 parts of aucubin, and 3 parts of a mixture of pinoresinol diglucoside and dehydrodiconiferyl diglucoside.

The preparation method of the eucommia ulmoides extract composition comprises the following steps:

(1) step (3), the same operation as in example 1;

(4) mixing the residual water extract after adsorption by HZ-820 type macroporous resin with distilled water eluent A, adjusting pH to 3 with citric acid, adsorbing with XAD-6 type macroporous resin, eluting with 1BV distilled water for removing impurities at an elution rate of 2.5BV/h to obtain distilled water eluent B for later use;

eluting with 3BV of 6% ethanol water solution at an elution rate of 3BV/h, and removing the eluent; eluting with 4BV of 17% ethanol aqueous solution with elution rate of 1.5BV/h, collecting eluate, adsorbing the eluate with NKA-2, eluting with 2BV of 12% ethanol aqueous solution with elution rate of 2BV/h to obtain chlorogenic acid;

(5) step (2), the operation is the same as example 1;

(6) mixing the prepared mixture of chlorogenic acid, aucubin, pinoresinol diglucoside and dehydrodiconiferyl alcohol diglucoside according to a ratio to obtain the eucommia ulmoides extract composition.

Comparative example 3

The only difference from example 1 is the preparation method.

A composition of eucommia ulmoides extract was prepared in the same manner as in example 1.

The preparation method of the eucommia ulmoides extract composition comprises the following steps:

(1) pulverizing Eucommiae cortex, adding 6 times of distilled water, adding 1.5 wt% sodium acetate, extracting at 70 deg.C for 50min, boiling for extracting for 1.5 hr, and filtering to obtain water extractive solution and residue;

(2) step (6), the same operation as in example 1 was conducted.

Comparative example 4

The only difference from example 1 is the preparation method.

A composition of eucommia ulmoides extract was prepared in the same manner as in example 1.

The preparation method of the eucommia ulmoides extract composition comprises the following steps:

(1) pulverizing Eucommiae cortex, adding 6 times of distilled water, adding 1.5 wt% polysorbate 80, extracting at 70 deg.C for 50min, boiling for 1.5 hr, and filtering to obtain water extractive solution and residue;

(2) step (6), the same operation as in example 1 was conducted.

Comparative example 5

The only difference from example 1 is the preparation method.

A composition of eucommia ulmoides extract was prepared in the same manner as in example 1.

The preparation method of the eucommia ulmoides extract composition comprises the following steps:

(1) step (2), the same operation as in example 1;

(3) adsorbing the water extract with H103 type macroporous resin, eluting with 2.5BV distilled water at an elution rate of 2BV/H to remove impurities, and eluting with distilled water A; eluting with 35% ethanol water solution of 4BV at an elution rate of 2.5BV/h to obtain aucubin;

(4) mixing the residual water extract after adsorption of H103 type macroporous resin with distilled water eluent A, adjusting pH to 3 with citric acid, adsorbing with XAD-6 type macroporous resin, eluting with 1BV distilled water for removing impurities at an elution rate of 2.5BV/H to obtain distilled water eluent B for later use;

eluting with 3BV of 6% ethanol water solution at an elution rate of 3BV/h, and collecting the eluate to obtain geniposide;

eluting with 4BV of 17% ethanol aqueous solution with elution rate of 1.5BV/h, collecting eluate, adsorbing the eluate with NKA-2, eluting with 2BV of 12% ethanol aqueous solution with elution rate of 2BV/h to obtain chlorogenic acid;

(5) step (6), the same operation as in example 1 was conducted.

Evaluation of Effect

Hypertension model test:

wistar rat, 240 plus 280g, SPF grade, provided by Qinglongshan animal breeding farm in Jiangning district of Nanjing;

dissolving N-nitro-L-arginine methyl ester (L-NAME) with normal saline to obtain final concentration of 0.05 g/ml;

the prepared mixtures of examples 1-4 and comparative examples 1-5 were suspended and dissolved with 0.5% CMC-Na to a final concentration of 0.05 g/ml;

captopril tablets: changzhou pharmaceutical factory (specification: 25mg x 100 tablets);

after the rats are taken and bred adaptively for 7 days, starting on day 8, injecting a molding agent L-NAME at a ratio of 10:00 per day of 0.25g/kg, continuously measuring the systolic pressure at 28 days of molding and 14:00 per rat for 3 times, and averaging the average systolic pressure of more than or equal to 160mm Hg as a molding success standard.

After molding, taking 110 successfully molded rats which are divided into 11 groups, 10 of each group are respectively a model group, a positive control group, an example 1-4 group and a comparative example 1-5 group, and taking 10 of non-molded rats as a blank control group;

administration: the daily ratio is 10:00, the blank control group is perfused with physiological saline 0.5g/kg daily, and the positive control group is fed with captopril tablets 25mg/kg daily; the model group is perfused with 0.5g/kg of physiological saline every day; the remaining groups (groups of examples 1-4 and comparative examples 1-5) were each intragastric administered at 0.5g/kg of the suspensions prepared in examples 1-4 and comparative examples 1-5; continuously administering for 30 days, wherein the administration period is normal diet, and measuring systolic pressure after the last day of administration is finished; in addition, 10mL of blood is taken from abdominal aorta of a rat, the abdominal aorta is kept still for 30min, centrifuged at 4000r/min for 10min, serum is separated, and rat serum endothelin-1 (ET-1) and vascular cell adhesion molecule-1 (VCAM-1) are tested. The results are shown in Table 1.

TABLE 1 rat blood index and blood pressure index changes before and after administration: (n＝10)

Note: the different letters in the same column have significant difference, and P is less than 0.05.

Therefore, the blank control group and the model group data have significant difference, which indicates that the molding is successful. In addition, the groups of examples 1 to 5 have significant differences compared with the model group, which shows that the eucommia ulmoides extract composition provided by the invention has better effect of treating hypertension and the curative effect is equivalent to that of the positive control group (has no significant difference). Meanwhile, it can be seen from the experimental data of comparative examples 1 to 5 and example 1 that the composition of each active ingredient and the extraction process of the active ingredients in the present invention have significant effects on the pharmaceutical effects of the eucommia ulmoides extract.

The above detailed description is specific to one possible embodiment of the present invention, and the embodiment is not intended to limit the scope of the present invention, and all equivalent implementations or modifications without departing from the scope of the present invention should be included in the technical scope of the present invention.