阅读说明：本技术 一种芹菜黄精酵素压片糖果及其用途和制备方法 (Celery and sealwort enzyme tablet candy and application and preparation method thereof ) 是由 范代娣 张艳宜 段志广 马晓轩 于 2020-05-12 设计创作，主要内容包括：本发明涉及一种由芹菜黄精酵素压片糖果,其原料粉包括：芹菜粉、黄精提取物、菊粉、玉米淀粉,且它们的质量份数如下：相对于10重量份的玉米淀粉,使用芹菜粉50～80份,黄精提取物5～25份,菊粉10～15份；本发明还涉及该压片糖果用于降血压保健品的用途及其制备方法。(The invention relates to a celery and rhizoma polygonati enzyme tablet candy, which comprises the following raw material powder: celery powder, a sealwort extract, inulin and corn starch, and the mass parts of the components are as follows: 50-80 parts of celery powder, 5-25 parts of rhizoma polygonati extract and 10-15 parts of inulin are used relative to 10 parts of corn starch by weight; the invention also relates to application of the tabletting candy in health care products for reducing blood pressure and a preparation method thereof.)

1. A celery and rhizoma polygonati enzyme tabletting candy is prepared by tabletting raw material powder and auxiliary materials, wherein the raw material powder is prepared by fermenting celery powder, a rhizoma polygonati extract, inulin and corn starch through lactic acid bacteria.

2. The celery and sealwort ferment tablet candy according to claim 1, wherein each gram of tablet candy comprises:

350-450 mu g of polygonatum polysaccharide,

rhizoma Polygonati flavone 120-180 μ g, and

apigenin 20-40 mg.

3. The celery and sealwort enzyme tabletting candy according to claim 1, wherein the celery powder, the sealwort extract, the inulin and the corn starch which are fermented by lactic acid bacteria are used in the following ratio in parts by weight when preparing the raw material powder: 50-80 parts of celery powder, 5-25 parts of rhizoma polygonati extract and 10-15 parts of inulin are used relative to 10 parts of corn starch.

4. The celery-sealwort enzyme tabletting candy according to claim 1, wherein the auxiliary materials comprise calcium hydrogen phosphate and magnesium stearate, and the dosage of the auxiliary materials expressed by mass parts is as follows:

when 100 parts of the raw meal are used, use is made of

1-4 parts of calcium bicarbonate,

0.5-1.5 parts of magnesium stearate.

5. The celery and sealwort ferment tablet candy according to claim 2, wherein the mass of the tablet candy in unit dose is 150mg to 450mg, preferably 300 mg.

6. The celery and sealwort ferment tablet candy according to claim 5, wherein the tablet form of the tablet candy is any one selected from the group consisting of oral tablets, buccal tablets, chewable tablets, orally disintegrating tablets and effervescent tablets, and preferably the tablet is oral tablet.

7. Use of the celery and sealwort ferment tablet candy according to any one of claims 1 to 6 in the preparation of health products and functional foods for preventing or treating hypertension.

8. The use according to claim 5, wherein the effective amount is 9 tablets/person/day when 300mg of the tabletted candy is used, for administration as a hypertensive health product.

9. The use according to claim 8, wherein, when 300mg of the tabletted confectionery product is used as a health product for treating hypertension, it is administered once in the morning, at noon and at night, each time in the same amount.

10. A method for manufacturing the celery and sealwort ferment tablet candy according to any one of claims 1 to 4 comprises the following specific steps:

-a step of obtaining celery powder;

-a step of preparing a seed liquid: the seed liquid is prepared by using lactobacillus plantarum, wherein the preservation number of the lactobacillus plantarum is CGMCCNO: 8198 parts of;

-a step of preparing a polygonatum extract: is prepared by extracting rhizoma polygonati decoction pieces;

-inoculation, fermentation steps: uniformly mixing the prepared celery powder, the prepared rhizoma polygonati extract, inulin and corn starch, adding the mixture into water, and inoculating a seed solution for fermentation;

-a homogenization, filtration step: homogenizing the fermented product under high pressure, filtering, and removing insoluble substance to obtain filtrate;

-concentration, drying step: concentrating the fermentation filtrate under reduced pressure to obtain concentrated solution, and spray drying the concentrated solution to obtain raw material powder;

-a tabletting step: tabletting to obtain the celery and sealwort enzyme tabletting candy.

Technical Field

The invention relates to the field of food engineering, in particular to the field of health care products. Specifically, the invention relates to a celery and rhizoma polygonati enzyme tablet candy for adjuvant therapy of hypertension, and application and a preparation method thereof.

Background

Hypertension is a disease which is caused by interaction of multiple factors such as heredity, environment and the like and is mainly characterized by continuous rise of systemic arterial blood pressure, symptoms of the hypertension are represented by dizziness, head distension, headache, eye distending pain, blurred vision, unstable standing and the like, clinically, the hypertension is generally represented by rise of systolic pressure (more than or equal to 140mmHg) and/or diastolic pressure (more than or equal to 90mmHg), the hypertension is a risk factor of multiple diseases such as cardiovascular and cerebrovascular diseases, kidney and the like and is also a main cause of death of the cardiovascular and cerebrovascular diseases, the most common complications are stroke, heart disease, kidney disease, peripheral vascular disease, eyeground disease and the like, wherein 70% of stroke and 50% of myocardial infarction are related to hypertension. According to the statistics data in 2013, the number of disabled people reaches 2 hundred million because more than 1000 million people die due to high systolic pressure in the world, and the monitoring and investigation data of the chronic diseases in China shows that the prevalence rate of hypertension of Chinese adults in 2010 is as high as 33.5%, and the estimated number of affected people reaches 3.3 million.

The sealwort is sweet in taste and neutral in nature, and the traditional Chinese medicine research shows that the sealwort has the effects of tonifying qi and yin, moistening lung and tonifying kidney, and contains active ingredients such as sealwort polysaccharide, steroid saponin, flavonoid and the like. Modern pharmacological studies show that the polygonatum sibiricum extract has various effects of preventing and treating cardiovascular diseases, resisting aging, resisting tumors, reducing blood sugar and the like, has obvious curative effects on symptoms such as headache and dizziness caused by hypertension, and has a certain reversing effect on damages to target organs of heart, brain and kidney caused by hypertension.

Celery leaves are sweet, bitter and cool in taste, and have the effects of clearing heat, stopping bleeding, calming the liver, dispelling wind and the like. Modern pharmacological researches show that apigenin in celery has an obvious blood pressure reducing effect, but active ingredients in fresh celery mainly comprise apigenin and are mainly concentrated in celery leaves, the researches show that the apigenin content in the celery leaves is 8-10 times of that of celery stems, and a plurality of researchers find that the apigenin can be converted into the apigenin under a certain condition, so that the apigenin content in the celery can be greatly improved, the existing method for converting the apigenin is mainly an acidolysis method, and no report is found on the research on the microbial fermentation conversion of the apigenin.

Disclosure of Invention

The tablet candy is prepared by mixing natural fresh celery leaves and a polygonatum sibiricum extract and converting and refining the mixture by a special fermentation technology of lactic acid bacteria, and is a pure natural green functional food.

The present application provides:

1. a celery and rhizoma polygonati enzyme tabletting candy is prepared by tabletting raw material powder and auxiliary materials, wherein the raw material powder is prepared by fermenting celery powder, a rhizoma polygonati extract, inulin and corn starch through lactic acid bacteria, and the auxiliary materials are added during tabletting.

2. The celery and sealwort ferment tablet candy according to item 1, wherein each gram of tablet candy comprises:

350-450 mu g of polygonatum polysaccharide,

rhizoma Polygonati flavone 120-180 μ g, and

apigenin 20-40 mg.

3. The celery and sealwort enzyme tabletting candy as in item 1, wherein the celery powder, the sealwort extract, the inulin and the corn starch which are fermented by lactic acid bacteria are used in the following proportions in parts by weight when preparing the raw material powder: 50-80 parts of celery powder, 5-25 parts of rhizoma polygonati extract and 10-15 parts of inulin are used relative to 10 parts of corn starch.

4. The celery-sealwort enzyme tabletting candy according to item 1, wherein the auxiliary materials comprise calcium hydrogen phosphate and magnesium stearate, and the dosage of the auxiliary materials expressed in parts by mass is as follows:

when 100 parts of the raw meal are used, use is made of

1-4 parts of calcium bicarbonate,

0.5-1.5 parts of magnesium stearate.

5. The celery-sealwort ferment tablet candy according to item 2, wherein the mass of the tablet candy in unit dose is 150mg to 450mg, preferably 300 mg.

6. The celery-sealwort ferment tablet candy according to the item 5, wherein the tablet form of the tablet candy is any one selected from the group consisting of an oral tablet, a buccal tablet, a chewable tablet, an orally disintegrating tablet and an effervescent tablet, and the oral tablet is preferred.

7. Use of the celery and polygonatum sibiricum enzyme tabletting candy according to any one of items 1 to 6 in preparation of health care products and functional foods for preventing or treating hypertension.

8. The use according to item 5, wherein the effective amount is 9 tablets/person/day when 300mg of the tabletted candy is used, for administration as a hypertensive health product.

9. The use according to item 8, wherein, when 300mg of the tabletted candy is used as a health care product for treating hypertension, the tabletted candy is administered once in the morning, at noon and at night, and the dose of each administration is the same.

10. A method for manufacturing celery and sealwort ferment tablet candy according to any one of items 1 to 4, which comprises the following specific steps:

-a step of obtaining celery powder;

-a step of preparing a seed liquid: the seed liquid is prepared by using lactobacillus plantarum, wherein the preservation number of the lactobacillus plantarum is CGMCCNO: 8198 parts of;

-a step of preparing a polygonatum extract: is prepared by extracting rhizoma polygonati decoction pieces;

-inoculation, fermentation steps: uniformly mixing the prepared celery powder, the prepared rhizoma polygonati extract, inulin and corn starch, adding the mixture into water, and inoculating a seed solution for fermentation;

-a homogenization, filtration step: homogenizing the fermented product under high pressure, filtering, and removing insoluble substance to obtain filtrate;

-concentration, drying step: concentrating the fermentation filtrate under reduced pressure to obtain concentrated solution, and spray drying the concentrated solution to obtain raw material powder;

-a tabletting step: tabletting to obtain the celery and sealwort enzyme tabletting candy.

11. The method of making a tabletted confection of item 10, wherein the step of obtaining celery powder is performed sequentially: harvesting celery leaves; removing impurities; sterilizing celery leaves; cutting celery leaves into pieces; freeze drying finely crushed celery leaves, and then crushing into celery powder.

12. The method of producing a tabletted confectionery according to item 10, wherein the step of preparing the seed liquid is carried out sequentially: inoculating Lactobacillus plantarum frozen at-80 deg.C into MRS culture medium with an inoculum size of 1%, and culturing in 32 deg.C anaerobic incubator until viable count reaches 10⁸cfu/mL, activated for 3 generations according to the method to obtain the lactobacillus seed solution.

13. The process for producing a tabletted candy according to item 10, wherein in the inoculating and fermenting step, the fermentation substrate is used in the following proportions in parts by mass: 50-80 parts of celery powder, 5-25 parts of rhizoma polygonati extract and 10-15 parts of inulin are used relative to 10 parts of corn starch by weight, then 5-8 times of water is added, the mixture is uniformly mixed and then is inoculated into the lactobacillus seed solution according to the amount of 25-35 mL seed solution/L mixed juice, and the mixture is stirred and fermented for 3-5 days at 36-38 ℃.

14. The method of producing a tabletted candy according to item 10, wherein the high pressure in the homogenizing, filtering step is 40 to 50MPa high pressure.

15. The method of producing a tabletted confectionery according to item 10, wherein in the concentrating and drying step, the density of the concentrated solution is 1.05 to 1.15 relative density.

16. The process for producing a tabletted candy according to item 10, wherein, in the tableting step, the raw material powder is uniformly mixed with calcium hydrogen phosphate and magnesium stearate and then subjected to tableting treatment, and the mass of the finished tablet is 150mg to 450mg, preferably 300 mg.

17. The process for producing a tabletted candy according to item 10, wherein,

in the step of preparing the polygonatum sibiricum extract, the polygonatum sibiricum extract is prepared according to the following alcohol extraction-water boiling method:

-an alcohol extraction step: carrying out reflux extraction for 1.5-2 hours according to a material-liquid ratio (rhizoma polygonati decoction pieces: ethanol) of 1: 8-10, repeatedly extracting for 2 times at an ethanol concentration of 70-80%, and respectively collecting filtrate and filter residue;

-a water boiling step: extracting according to a material-liquid ratio (alcohol extraction filter residue: water) of 1: 15-20 for 1.5-2 hours, repeatedly extracting for 2 times, discarding filter residue, and combining with alcohol extraction filtrate to obtain mixed filtrate;

-a preparation step: and concentrating the mixed filtrate under reduced pressure to obtain an extract with the relative density of 1.05-1.15, and performing spray drying to obtain the polygonatum sibiricum extract.

The technical scheme of the invention can be summarized as follows:

the core advantage of the tabletted confectionery product made in accordance with the present application is that by fermenting celery powder, polygonatum extract, inulin, corn starch and lactic acid bacteria together to make a raw material powder, an unexpectedly high apigenin content in the product is obtained, which may be as high as 40mg/g according to analysis.

2, the celery powder, the sealwort extract, the inulin, the corn starch and the lactic acid bacteria are fermented together to prepare the raw material powder, and the slightly sweet excellent taste is unexpectedly obtained. The tablet candy can be used as a buccal tablet for people to use, and the application scene of the tablet candy as a health-care product is expanded, so that the tablet candy is popular with consumers.

3. By adding calcium hydrogen phosphate and magnesium stearate into the raw material powder before tabletting, the bonding phenomenon of the raw material powder in the tabletting process and the lubrication degree and mouthfeel of the finally prepared tabletting candy are well controlled.

4. By preparing the polygonatum sibiricum extract by using the alcohol extraction-water boiling method and further increasing the content of the effective components by lactic acid fermentation, the polygonatum sibiricum polysaccharide content (up to 450 mug/g) and the polygonatum sibiricum flavone content (up to 180 mug/g) with higher concentration are unexpectedly obtained in the finished product.

Detailed Description

It is noted that certain terms are used throughout the description and claims to refer to particular components. It will be understood by those skilled in the art that various terms may be used to refer to a single component. The present specification and claims do not intend to distinguish between components that differ in noun but intend to distinguish between components that differ in function. In the following description and in the claims, the terms "include" and "comprise" are used in an open-ended fashion, and thus should be interpreted to mean "include, but not limited to. The description which follows is a preferred embodiment of the invention, but is made for the purpose of illustrating the general principles of the invention and not for the purpose of limiting the scope of the invention. The scope of the present invention is defined by the appended claims.

The application provides celery sealwort ferment tablet candy product in the first aspect.

In one embodiment, provided is a celery and polygonatum sibiricum enzyme tablet candy, which comprises the following raw material powder: celery powder, a sealwort extract, lactic acid bacteria, inulin and corn starch, and the mass parts of the components are as follows: 50-80 parts of celery powder, 5-25 parts of rhizoma polygonati extract, 2-5 parts of lactic acid bacteria and 10-15 parts of inulin are used relative to 10 parts of corn starch by weight.

In another embodiment, the raw material powder is prepared by fermenting celery powder, rhizoma polygonati extract, lactic acid bacteria, inulin and corn starch.

In another embodiment, in order to prepare the tablet candy from the raw material powder, the raw material powder is optionally blended with calcium hydrogen phosphate and magnesium stearate, and the mass parts of the raw material powder are as follows: 1-4 parts of calcium hydrophosphate and 0.5-1.5 parts of magnesium stearate are used for 100 parts of raw material powder.

Specifically, the celery powder can be 50 parts, 55 parts, 60 parts, 65 parts, 70 parts, 75 parts and 80 parts by dry weight of each component in the raw material powder; the sealwort extract can be 5 parts, 10 parts, 15 parts, 20 parts or 25 parts; the lactic acid bacteria can be 2 parts, 3 parts, 4 parts and 5 parts; and inulin can be 10 parts, 11 parts, 12 parts, 13 parts, 14 parts and 15 parts.

In the context of the present specification, "inulin" is a reserve polysaccharide in plants. It is mainly derived from plants, and its source has been found to be 36000 kinds, including 11 families of dicotyledonous plants such as Compositae, Campanulaceae, Gentianaceae, etc., and 11 families of monocotyle, Gramineae. For example, inulin is abundant in Jerusalem artichoke, tubers of chicory, root tuber of Paeonia suffruticosa (Dali chrysanthemum), and roots of Cirsium japonicum, wherein inulin content of Jerusalem artichoke is the highest. The inulin molecules are polymerized by 31 beta-D-fructofuranose and 1-2 pyranoinulin residues, and the fructose residues can be connected through beta-2, 1-bonds. The inulin is linear straight-chain polysaccharide formed by linking D-fructose through beta (1 → 2) glycosidic bonds, the tail end of the linear straight-chain polysaccharide is usually provided with a glucose residue, the polymerization Degree (DP) is 2-60, wherein inulin with the average polymerization degree DP less than or equal to 9 is also called short-chain inulin, and inulin extracted from natural plants simultaneously contains long chains and short chains. Inulin has the formula GFn, wherein G represents the terminal glucose unit, F represents the fructose molecule, and n represents the number of fructose units. In the technical scheme of the application, inulin is decomposed into monosaccharide through fermentation, so that the sweetness of the tablet candy can be increased, a carbon source is provided for lactobacillus fermentation, and the taste of the tablet candy is improved

In the context of the present specification, "lactic acid bacteria" (LAB) are a general term for a group of bacteria that are capable of utilizing fermentable carbohydrates to produce large amounts of lactic acid. The bacteria are widely distributed in nature, have abundant species diversity, at least comprise 18 genera, and more than 200. Except for a very small number, most of them are flora which are indispensable in human body and have important physiological functions, and are widely present in intestinal tracts of human body. In the technical scheme of the application, the lactic acid bacteria can convert apigenin (essentially glycoside) rich in celery leaves into apigenin (essentially flavonoid) through a biotransformation process in anaerobic fermentation, so that the content of the apigenin with an obvious blood pressure reducing effect is greatly improved. Through lactic acid bacteria fermentation, the taste of the raw material powder of the tabletted candy is slightly sour and sweet, the method skillfully combines a lactic acid fermentation process, a polysaccharide degradation process and an apigenin biotransformation process together in a fermentation process, and unexpectedly and efficiently completes the core step of apigenin biotransformation.

Specifically, 1 part, 2 parts, 3 parts and 4 parts of calcium hydrogen phosphate are added into the raw material powder before the pressed candy is pressed; the magnesium stearate added may be 0.5 parts, 0.7 parts, 0.9 parts, 1.1 parts, 1.3 parts, 1.5 parts.

In the context of this specification, "calcium hydrogen phosphate" is a food additive in the form of calcium hydrogen phosphate powder which is commonly commercially available for use as a leavening agent. In the technical scheme of the application, the calcium bicarbonate has two functions, namely, the calcium bicarbonate can be used as a calcium supplement in a health product on one hand, and can be used as a leavening agent on the other hand, so that the caking phenomenon frequently occurring in the production process is improved. The technical scheme of the application ingeniously utilizes the multiple functions of the calcium hydrophosphate and finds out the proper dosage of the calcium hydrophosphate to achieve the balance of economy and effect.

In the context of the present specification, "magnesium stearate" is a food additive in the form of magnesium stearate powder, commonly commercially available, for use as a lubricant. In the technical scheme of this application, calcium bicarbonate has two aspects effects in this application, can use the fluency that improves the preforming technology as the lubricant on the one hand, can use as the thickening agent on the other hand to improve the taste of preforming candy on the other hand. The technical scheme of the application skillfully utilizes the multiple functions of the magnesium stearate and gropes out the proper dosage of the magnesium stearate to achieve the balance of economy and effect.

In one embodiment, the mass of the unit dose of tabletted confectionery is between 150mg and 450mg, preferably 300 mg; the content of polygonatum polysaccharide detected in the tabletted candy with unit dose is 350-450 mug/g, the content of polygonatum flavone is 120-180 mug/g, and the content of apigenin is 20-40 mg/g.

Specifically, the mass of the tabletted confectioneries of a unit dose may be 150mg, 200mg, 250mg, 300mg, 350mg, 400mg, 450 mg; the content of rhizoma Polygonati polysaccharide detected in the tabletted candy of unit dose can be 350 μ g/g, 370 μ g, 390 μ g/g, 410 μ g/g, 430 μ g/g, 450 μ g/g, while the content of rhizoma Polygonati flavone can be 120 μ g/g, 130 μ g/g, 140 μ g/g, 150 μ g/g, 160 μ g/g, 170 μ g/g, 180 μ g/g; the content of apigenin can be 20mg, 25mg, 30mg, 35mg and 40 mg.

In the context of this specification, "tableting" is a process of making tablets using dry-forming, i.e. pressing a raw material powder into a tablet or ring shape using a tablet press. Generally, tablets can be classified into compressed tablets and die-cast tablets according to the preparation method. As used herein, "compressed tablets" are used interchangeably with "compressed tablets". For "tableting", the starting powder for molding may be completely dry or have some moisture. The powder is placed in a mold during molding, and a quantity of a molding agent is usually added to facilitate demolding and adjustment of the pore structure. When tabletting, the powders are bonded to each other mainly by van der waals forces. Capillary pressure also increases the bonding capacity in the presence of water. When the molding pressure is not too large, the pore structure and specific surface change. At very high pressures, there is a possibility that the chemical structure may change in addition to the physical structure. In the context of this specification, a "tabletted candy" is a description of the tablet QS product by a health care product manufacturer and is not generally considered a candy by the general public. It is to be understood that tabletted confectioneries are only one description of the appearance of a health product by the manufacturer. The 'tablet candy' can be produced by the steps of granulation, adhesion, compression molding and the like. In the solution of the present application, the mass of the tabletted confectionery product of a given unit dose is between 150mg and 450mg, preferably 300 mg; the tablet candy with the size in the range is suitable for human oral administration, is very convenient to chew, hold or swallow, and is beneficial to improving the acceptance of users.

In a second aspect, the present application provides the use of the tabletted confectionery product as a health food product.

In one embodiment, the application of the celery and sealwort ferment tablet candy in preparing health products and functional foods for preventing or treating hypertension is provided. Wherein, when 300mg of the pressed candy is used as a health care product for treating hypertension, the dosage can be 3 tablets, 6 tablets, 9 tablets, 12 tablets and 15 tablets per person per day; most preferably 9 tablets/person/day. Wherein, when 300mg of the tablet candy is used as a health care product for treating hypertension, the tablet candy is taken once in the morning, at noon and at night, and the dosage of each time is the same. In the technical scheme of the application, the tabletted candy can be a tablet, a chewable tablet, a buccal tablet, an effervescent tablet and the like which are generally swallowed, the dosage form can be any common pharmaceutical dosage form without special limitation as long as the dosage of the tabletted candy meets the requirement of the tabletted candy serving as health-care food; however, depending on the dosage form to be produced, the tablet excipients used will vary, and are well recognized in the general pharmaceutical art and are commercially available. For tablets intended for ordinary swallowing, the usual excipients are usually fillers, binders, lubricants. For chewable tablets, sweeteners are additionally used. For buccal tablets, flavors such as peppermint are also used more additionally. For effervescent tablets, disintegrants are also used more additionally. When the effervescent tablet is prepared, obvious marks need to be given on the outer package of the product and the instruction so as to prevent a user from taking the effervescent tablet directly by mistake. The preferred dosage form according to the tabletted confectionery formulations of the present application is an oral tablet. According to the formula of the tablet candy, aiming at the health-care function of reducing blood pressure, the known apigenin is converted into apigenin to play a role in reducing blood pressure, and the content of polygonatum polysaccharide and flavone brought by the fermentation process of lactic acid bacteria is increased to play a synergistic effect.

The application provides a manufacturing method of celery and sealwort ferment tablet candy in a third aspect.

In one embodiment, a method for manufacturing the celery sealwort ferment tablet candy is provided, which comprises the following specific steps:

-a step of obtaining celery powder: harvesting celery leaves; removing impurities; sterilizing celery leaves; cutting celery leaves into pieces; freeze drying finely crushed celery leaves, and then crushing into celery powder;

-a step of preparing a seed liquid: taking lactobacillus plantarum frozen at minus 80 ℃, wherein the preservation number is CGMCC NO: 8198 inoculating 0.5-1.5% of MRS culture medium, and culturing in 32 deg.C anaerobic incubator until viable count reaches 10⁸Activating cfu/mL for at least 3 generations according to the method to obtain a lactobacillus seed solution;

-inoculation, fermentation steps: uniformly mixing the prepared celery powder, the sealwort extract, the inulin and the corn starch, adding 5-8 times of water, uniformly mixing, then adding the lactobacillus seed liquid according to the amount of 25-35 mL of seed liquid/L of mixed juice, stirring and fermenting at 36-38 ℃ for 3-5 days;

-homogenization, filtration: homogenizing the fermentation product obtained after fermentation under high pressure of 40-50 MPa, filtering, and removing insoluble substances in thallus residues to obtain filtrate;

-concentration, spray drying: concentrating the fermentation filtrate under reduced pressure to obtain a concentrated solution with the relative density of 1.05-1.15, and performing spray drying on the concentrated solution to obtain raw material powder;

-a tabletting step: and uniformly mixing the raw material powder with calcium hydrophosphate and magnesium stearate, and tabletting to obtain the celery sealwort ferment tablet candy. In the tableting step, the mass of the finished tablet pressed is from 150mg to 450mg, preferably 300 mg.

Specifically, the inoculation amount may be 0.5%, 0.7%, 0.9%, 1.1%, 1.3%, 1.5%, and the percentages are mass percentages.

Specifically, the activation may be performed for 3, 4, 5, 6, and most preferably 3 generations.

Specifically, the temperature for fermentation can be 36 deg.C, 36.2 deg.C, 36.4 deg.C, 36.6 deg.C, 36.8 deg.C, 37 deg.C, 37.2 deg.C, 37.4 deg.C, 37.6 deg.C, 37.8 deg.C, 38 deg.C.

Specifically, when the high-pressure homogenization treatment is performed, the high pressure to be used may be 40MPa, 42MPa, 44MPa, 46MPa, 48MPa, or 50 MPa.

In the context of this specification, CGMCC NO means the collection number of the China general microbiological culture Collection center. The center is located at the institute of microbiology, academy of sciences of China. Specifically, the technical scheme of the application adopts a preservation number of CGMCC NO: 8198 Lactobacillus plantarum. The lactobacillus plantarum is one of lactobacillus, the optimal growth temperature of the lactobacillus plantarum is 30-35 ℃, the lactobacillus is anaerobic or facultative anaerobic, the strain is in a straight or bent rod shape, is single or sometimes in a pair or chain shape, the optimal pH value is about 6.5, and the lactobacillus plantarum belongs to homotype fermentation lactobacillus. The bacterium is different from other lactic acid bacteria in that the number of viable bacteria of the bacterium is higher, a large amount of acid can be produced, the PH value in water is stable and not increased, and the produced acidic substances can degrade heavy metals; since this bacterium is an anaerobic bacterium (facultative aerobe), it can produce specific lactobacillin during the propagation process. "Lactobacillus plantarum" can be used in the field of health products, and its known effects are as follows: firstly, has a certain immunoregulation function; ② the medicine has inhibiting effect on pathogenic bacteria; ③ reducing the content of serum cholesterol and preventing cardiovascular diseases; fourthly, maintaining the balance of the flora in the intestinal tract; promoting the absorption of nutrient substances; sixthly, relieving lactose intolerance; inhibit the formation of tumor cells, etc. In the solution of the present application, both the above known lactic acid bacteria health-care effect and its effect not known in the prior art are utilized: the method skillfully combines the lactic acid fermentation process, the polysaccharide degradation process and the apigenin biotransformation process together in a primary fermentation process, and unexpectedly and efficiently completes the core step of apigenin biotransformation. In the context of the present specification, "activation" refers to bacterial species resuscitation.

In the context of the present specification, "fermentation with stirring at 36 to 38 ℃ for 3 to 5 days" means fermentation of lactic acid bacteria under low dissolved oxygen conditions. By "low dissolved oxygen" is meant that the dissolved oxygen in the water is less than 5 mg/L. Generally, dissolved oxygen is closely related to the partial pressure of oxygen in air, atmospheric pressure, water temperature and water quality, and approximately 9mg/L of dissolved oxygen is present in pure water at 20 ℃ and 100 kPa. Some organic compounds are biodegraded under the action of aerobic bacteria, consuming dissolved oxygen in water. Water temperature and stirring are main factors influencing dissolved oxygen, and the lower the water temperature is, the higher the content of the dissolved oxygen in the water is. Molecular oxygen dissolved in water is known as dissolved oxygen and is commonly referred to as DO and is expressed in milligrams of oxygen per liter of water. In the technical scheme of the application, the DO value is mainly adjusted by adjusting the fermentation temperature and the stirring rate.

In the context of this specification, "spray drying" means that after atomization of the diluent in a drying chamber, the moisture rapidly vaporizes upon contact with hot air to yield a dried product. The method can directly dry the solution or emulsion into powder or granular product, and can omit the procedures of evaporation, pulverization, etc. In the technical scheme of the application, the raw material powder used for tabletting is prepared by a spray drying method. The raw material powder obtained by the method has extremely low water content and fineness of …, and is very suitable for the subsequent tabletting process.

In the context of this specification, "tableting" is a process of making tablets using dry-forming, i.e. pressing a raw material powder into a tablet or ring shape using a tablet press. Generally, tablets can be classified into compressed tablets and die-cast tablets according to the preparation method. As used herein, "compressed tablets" are used interchangeably with "compressed tablets". For "tableting", the starting powder for molding may be completely dry or have some moisture. The powder is placed in a mold during molding, and a quantity of a molding agent is usually added to facilitate demolding and adjustment of the pore structure. When tabletting, the powders are bonded to each other mainly by van der waals forces. Capillary pressure also increases the bonding capacity in the presence of water. When the molding pressure is not too large, the pore structure and specific surface change. At very high pressures, there is a possibility that the chemical structure may change in addition to the physical structure. In the solution of the present application, the mass of the tabletted confectionery product of a given unit dose is between 150mg and 450mg, preferably 300 mg; the tablet candy in this range is suitable for oral administration by human, and is convenient for chewing, buccal administration and swallowing, and is beneficial to improving the user's acceptance, and tablets in this quality range are easy to prepare. Besides the pressure used by the tablet press, the quality of the tabletted candies and the factors influencing the tabletting process, the main factors are the auxiliary materials used by the tabletted candies. The most preferred dosage form for the embodiments of the present application is an oral tablet. From the viewpoint of facilitating the tabletting process and the taste of the tablet to be taken by the user, it is recommended to use auxiliary materials such as calcium hydrogen phosphate, magnesium stearate, corn starch, microcrystalline cellulose and the like.

In another embodiment, the polygonatum extract used in the inoculation and fermentation steps is prepared by the following alcohol extraction-water decoction method which adopts polygonatum decoction pieces as raw materials:

-an alcohol extraction step: carrying out reflux extraction according to a material-liquid ratio (rhizoma polygonati decoction pieces: ethanol) of 1: 8-10 for 1.5-2 hours, repeatedly extracting for at least 2 times at an ethanol concentration of 70-80%, and respectively collecting filtrate and filter residue;

-a water boiling step: extracting according to a material-liquid ratio (alcohol extraction filter residue: water) of 1: 15-20 for 1.5-2 hours, repeatedly extracting for 2 times, discarding filter residue, and combining with alcohol extraction filtrate to obtain mixed filtrate;

-a preparation step: and concentrating the mixed filtrate under reduced pressure to obtain an extract with the relative density of 1.05-1.15, and performing spray drying to obtain the polygonatum sibiricum extract.

Specifically, in the alcohol extraction step, the material-liquid ratio (rhizoma polygonati decoction pieces: ethanol) can be 1:8, 1:8.5, 1:9, 1:9.5 and 1: 10; the extraction time can be 1.5 hours, 1.6 hours, 1.7 hours, 1.8 hours, 1.9 hours and 2 hours; and the ethanol concentration may be 70%, 72%, 74%, 76%, 78%, 80%; the number of extraction times may be 2, 3, 4, 5, most preferably 2.

Specifically, in the water boiling step, the material-liquid ratio (alcohol extraction filter residue: water) can be 1:15, 1:16, 1:17, 1:18, 1:19 and 1: 20; the extraction time can be 1.5 hours, 1.6 hours, 1.7 hours, 1.8 hours, 1.9 hours and 2 hours; the number of extraction times may be 2, 3, 4, 5, most preferably 2.

In the context of this specification, the "alcohol extraction-water boiling" method conforms to the general definition in the chemical field, and is essentially an extraction process. In the technical scheme of the application, the main target extracts of the rhizoma polygonati extract are rhizoma polygonati polysaccharide and rhizoma polygonati flavone which are polar molecules, so that ethanol and water are adopted as liquid phase media in the extraction process, and the rhizoma polygonati polysaccharide and the rhizoma polygonati flavone can be extracted under mild conditions on the premise of not damaging the chemical structure of the target extract (the rhizoma polygonati flavone is mainly dissolved in ethanol, and the rhizoma polygonati polysaccharide is mainly dissolved in water). In the context of this specification, "spray drying" means that after atomization of the diluent in a drying chamber, the moisture rapidly vaporizes upon contact with hot air to yield a dried product. The method can directly dry the solution or emulsion into powder or granular product, and can omit the procedures of evaporation, pulverization, etc. In the technical scheme of the application, the polygonatum sibiricum extract is prepared by a spray drying method from the filtrate obtained by the extraction process. The sealwort extract obtained by the method has extremely low water content and reasonable fineness, and is very suitable for subsequent inoculation and fermentation processes.

The present invention will be described in further detail with reference to examples, which are provided only for illustrating the present invention and are not intended to limit the scope of the present invention. The examples section of the present application consists of "preparation examples" and "test examples". Materials, reagents and the like used in the respective examples are commercially available unless otherwise specified.

Specific embodiments of the present invention will be described in detail below. While specific embodiments of the invention are shown herein, it should be understood that the invention may be embodied in various forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art.

Preparation example 1 preparation of celery and sealwort enzyme tabletted candy

According to the invention, the preparation of the rhizoma polygonati extract in the celery rhizoma polygonati enzyme tabletting candy is realized by the following steps:

1) reflux-extracting rhizoma Polygonati decoction pieces (from first-grade product of Anhui Yuanheng agriculture Limited liability company) at a material-to-liquid ratio of 1:8 with ethanol for 1.5 hr and ethanol concentration of 70% for 2 times, and collecting filtrate and residue respectively.

2) Extracting the filter residue after alcohol extraction in the step 1) with water according to the ratio of material to liquid of 1:15 for 1.5 hours, repeatedly extracting for 2 times, discarding the filter residue, and combining the filter residue with the alcohol extraction filtrate in the step 1) to obtain a mixed filtrate.

3) Concentrating the mixed filtrate obtained in the step 2) under reduced pressure to obtain an extract with the relative density of 1.05, and performing spray drying to obtain the polygonatum sibiricum extract.

According to the celery and sealwort ferment tablet candy, the preparation method is realized through the following steps:

1) and (4) checking: harvesting fresh celery leaves, removing weeds, washing away impurities such as sludge by clear water, and using after the inspection is qualified.

2) And (3) disinfection: sterilizing the cleaned fresh celery leaves by using ultraviolet rays.

3) Cutting: cutting sterilized fresh celery leaves into pieces with a width of 0.6 cm.

4) Drying and crushing: freeze-drying the cut celery leaves in the step 3) and crushing into celery leaf powder.

5) Preparing a lactobacillus seed solution: inoculating-80 deg.C frozen Lactobacillus plantarum CGMCC8198 into certain amount of MRS culture medium with an inoculum size of 1%, and culturing in 32 deg.C anaerobic incubator until viable count reaches 10⁸cfu/mL, activated for 3 generations according to the method to obtain the lactobacillus seed solution.

6) Inoculation and fermentation: uniformly mixing 50 parts of celery powder obtained in the step 4) with 5 parts of rhizoma polygonati extract, 10 parts of inulin and 8 parts of corn starch, adding 5 times of water, uniformly mixing, inoculating the seed liquid obtained in the step 5) according to the amount of 26mL of seed liquid/L of mixed juice, and stirring and fermenting for 4 days at 36.5 ℃.

7) Primary homogenizing and filtering: homogenizing the fermentation product obtained after the fermentation in the step 6) under 45MPa, filtering, and removing insoluble substances in thallus residues to obtain filtrate.

8) Concentration and spray drying: and (4) concentrating the fermentation filtrate obtained in the step (7) under reduced pressure to obtain a concentrated solution with the relative density of 1.05, and performing spray drying on the concentrated solution to obtain the raw material powder before tabletting.

9) Uniformly mixing the raw material powder (100 parts) in the step 8) with 1.5 parts of calcium hydrophosphate and 0.6 part of magnesium stearate, granulating and tabletting to obtain the celery sealwort ferment tabletting candy 1 for the subsequent test examples.

The celery leaf powder in the step 4) is not detected to be apigenin by high performance liquid chromatography.

Detecting the apigenin content of the celery and sealwort enzyme tabletting candy in the step 9) by using a high performance liquid chromatography method to be 25mg/g, detecting the sealwort polysaccharide content by using a phenol-sulfuric acid method to be 370 mu g/g, and detecting the sealwort total flavone content by using a spectrophotometric method to be 140 mu g/g.

Here, the method conditions of the above three chemical analysis methods are:

A) high performance liquid chromatography (for detecting apigenin content)

-a chromatographic column: orca C185 μm 250mm × 4.6mm (inside diameter) or equivalent;

-a mobile phase: methanol + water (60+ 40);

-flow rate: 1 mL/min;

-the detection wavelength: 268 nm;

-sample size: 10 μ L.

B) Phenol-sulfuric acid method (for detecting rhizoma Polygonati polysaccharide content)

Drawing a standard curve: taking 11 test tubes with 20mL scales, numbering from 0 to 5 respectively, adding standard glucose solution 0, 0.2, 0.6, 1.0, 1.4 and 1.8 respectively, supplementing the rest with distilled water (total amount is 2mL), adding 9% phenol solution 1mL in sequence, shaking up, and keeping for 5 to 20s from the front of tube liquid. 5mL of concentrated sulfuric acid was added and shaken up. The colorimetric solution was left at a constant temperature for 30min with a total volume of 8 mL. And (4) developing color. And then, taking a blank as a reference, carrying out colorimetric determination at a wavelength of 485nm, and drawing a standard curve by taking the sugar content as an abscissa and the optical density as an ordinate.

And (3) sample determination: 0.5mL of the sample solution was aspirated into the test tube (repeated 2 times), 1.5mL of distilled water was added, and phenol and concentrated sulfuric acid solutions were sequentially added in the same procedure as for preparing a standard curve, followed by color development and measurement of absorbance. The amount of sugar was calculated from a standard linear equation and the sugar content in the test sample was calculated.

C) Spectrophotometric method (for detecting rhizoma Polygonati total flavone content)

Drawing a standard curve: accurately sucking 0, 0.50, 1.00, 2.00, 3.00 and 4.00ml of rutin standard solution (equivalent to 0, 75, 150, 300, 450 and 600ug of rutin), transferring into a 10ml graduated colorimetric tube, adding 30% ethanol solution to 5ml, adding 0.3ml of 5% sodium nitrite solution respectively, shaking, standing for 5min, adding 0.3ml of 10% aluminum nitrate solution, shaking uniformly, standing for 6min, adding 2ml of 1.0mol/L sodium hydroxide solution, and fixing the volume to the graduation by using 30% ethanol. Shaking, standing for 15min, measuring absorbance at 510nm wavelength, drawing a standard curve with a zero tube as blank, rutin content (ug) as abscissa and absorbance as ordinate, and calculating correlation coefficient (r).

And (3) sample determination: according to the content of the total flavonoids in the sample, taking a solution to be detected with a proper volume, and performing absorbance determination at 510nm according to the standard curve preparation operation steps (if the sample solution has precipitates, the sample solution is filtered and then determined).

And (4) calculating a result: according to the standard working curve, the rutin content equivalent to the absorbance of the sample is calculated, and the total flavone content is calculated according to the following formula:

in the formula: x-total flavone content in sample, g/100g or g/100 ml;

m₁-calculating the amount of flavone, μ g, in the solution to be tested according to a standard curve;

m-sample mass or sample volume, g or ml;

V₁-volume for sample extract determination, ml;

V₂total volume of sample extract, ml.

Hereinafter, the analysis of these three chemicals also uses the above working conditions.

The unfermented celery powder and the unfermented polygonatum extract are uniformly mixed according to the proportion mentioned in the preparation example 1, granulated and tabletted to obtain the preparation example 1-a control tablet.

Preparation example 2 preparation of celery and sealwort enzyme tabletted candy

According to the invention, the preparation of the rhizoma polygonati extract in the celery rhizoma polygonati enzyme tabletting candy is realized by the following steps:

1) extracting rhizoma Polygonati decoction pieces with ethanol at a ratio of 1:8 under reflux for 2 hr, extracting with 75% ethanol for 2 times, and collecting filtrate and residue respectively.

2) Extracting the filter residue after alcohol extraction in the step 1) with water according to the ratio of material to liquid of 1:18 for 1.5 hours, repeatedly extracting for 2 times, discarding the filter residue, and combining the filter residue with the alcohol extraction filtrate in the step 1) to obtain a mixed filtrate.

3) Concentrating the mixed filtrate in the step 2) under reduced pressure to obtain an extract with the relative density of 1.08, and performing spray drying to obtain the sealwort extract.

According to the celery and sealwort ferment tablet candy, the preparation method is realized through the following steps:

1) and (4) checking: harvesting fresh celery leaves, removing weeds, washing away impurities such as sludge by clear water, and using after the inspection is qualified.

2) And (3) disinfection: sterilizing the cleaned fresh celery leaves by using ultraviolet rays.

3) Cutting: cutting sterilized fresh celery leaves into pieces with a width of 0.8 cm.

4) Drying and crushing: freeze-drying the cut celery leaves in the step 3) and crushing into celery leaf powder.

5) Preparing a lactobacillus seed solution: inoculating-80 deg.C frozen Lactobacillus plantarum CGMCC8198 into certain amount of MRS culture medium with an inoculum size of 1%, and culturing in 32 deg.C anaerobic incubator until viable count reaches 10⁸cfu/mL, activated for 3 generations according to the method to obtain the lactobacillus seed solution.

6) Inoculation and fermentation: uniformly mixing 60 parts of celery powder obtained in the step 4) with 8 parts of rhizoma polygonati extract, 12 parts of inulin and 10 parts of corn starch, adding 6 times of water, uniformly mixing, inoculating the seed liquid obtained in the step 5) according to the amount of 28mL of seed liquid/L of mixed juice, and stirring and fermenting for 3 days at 37 ℃.

7) Primary homogenizing and filtering: homogenizing the fermentation product obtained after the fermentation in the step 6) under 45MPa, filtering, and removing insoluble substances in thallus residues to obtain filtrate.

8) Concentration and spray drying: and (4) concentrating the fermentation filtrate obtained in the step (7) under reduced pressure to obtain a concentrated solution with the relative density of 1.1, and performing spray drying on the concentrated solution to obtain the raw material powder before tabletting.

9) Uniformly mixing the raw material powder (100 parts) in the step 8) with 2 parts of calcium hydrophosphate and 0.8 part of magnesium stearate, granulating and tabletting to obtain the celery sealwort ferment tabletting candy 2 for subsequent efficacy tests.

The celery leaf powder in the step 4) is not detected to be apigenin by high performance liquid chromatography.

Detecting the apigenin content of the celery and sealwort enzyme tabletting candy in the step 9) by using a high performance liquid chromatography method to be 30mg/g, detecting the sealwort polysaccharide content by using a phenol-sulfuric acid method to be 390 mu g/g, and detecting the sealwort total flavone content by using a spectrophotometric method to be 150 mu g/g.

Mixing the unfermented celery powder and the unfermented rhizoma Polygonati extract according to the proportion mentioned in preparation example 2, granulating, and tabletting to obtain preparation example 2-control tablet.

Preparation example 3 preparation of celery and polygonatum sibiricum enzyme tabletted candy

According to the invention, the preparation of the rhizoma polygonati extract in the celery rhizoma polygonati enzyme tabletting candy is realized by the following steps:

1) extracting rhizoma Polygonati decoction pieces with ethanol at a ratio of 1:9 under reflux for 2 hr, extracting with 75% ethanol for 2 times, and collecting filtrate and residue respectively.

2) Extracting the filter residue after alcohol extraction in the step 1) with water according to the ratio of material to liquid of 1:20 for 2 hours, repeatedly extracting for 2 times, discarding the filter residue, and combining the filter residue with the alcohol extraction filtrate in the step 1) to obtain mixed filtrate.

3) Concentrating the mixed filtrate obtained in the step 2) under reduced pressure to obtain an extract with the relative density of 1.1, and performing spray drying to obtain the polygonatum sibiricum extract.

According to the celery and sealwort ferment tablet candy, the preparation method is realized through the following steps:

1) and (4) checking: harvesting fresh celery leaves, removing weeds, washing away impurities such as sludge by clear water, and using after the inspection is qualified.

2) And (3) disinfection: sterilizing the cleaned fresh celery leaves by using ultraviolet rays.

3) Cutting: cutting sterilized fresh celery leaves into pieces with a width of 0.8 cm.

4) Drying and crushing: freeze-drying the cut celery leaves in the step 3) and crushing into celery leaf powder.

5) Preparing a lactobacillus seed solution: inoculating-80 deg.C frozen Lactobacillus plantarum CGMCC8198 into certain amount of MRS culture medium with an inoculum size of 1%, and culturing in 32 deg.C anaerobic incubator until viable count reaches 10⁸cfu/mL, activated for 3 generations according to the method to obtain the lactobacillus seed solution.

6) Inoculation and fermentation: uniformly mixing 70 parts of celery powder obtained in the step 4) with 12 parts of rhizoma polygonati extract, 13 parts of inulin and 12 parts of corn starch, adding 8 times of water, uniformly mixing, inoculating the seed liquid obtained in the step 5) according to the amount of 30mL of seed liquid/L of mixed juice, and stirring and fermenting for 4 days at 37 ℃.

7) Primary homogenizing and filtering: homogenizing the fermentation product obtained after fermentation in the step 6) under 50MPa, filtering, and removing insoluble substances in thallus residues to obtain filtrate.

8) Concentration and spray drying: and (4) concentrating the fermentation filtrate obtained in the step (7) under reduced pressure to obtain a concentrated solution with the relative density of 1.05, and performing spray drying on the concentrated solution to obtain the raw material powder before tabletting.

9) Uniformly mixing the raw material powder (100 parts) in the step 8) with 3 parts of calcium hydrophosphate and 1 part of magnesium stearate, granulating and tabletting to obtain the celery sealwort ferment tabletting candy 3 for subsequent efficacy tests.

The celery leaf powder in the step 4) is not detected to be apigenin by high performance liquid chromatography.

Detecting the apigenin content of 35mg/g by using a high performance liquid chromatography, detecting the polygonatum polysaccharide content of 400 mu g/g by using a phenol-sulfuric acid method, and detecting the polygonatum total flavone content of 145 mu g/g by using a spectrophotometry in the step 9).

Mixing the unfermented celery powder and the unfermented polygonatum extract according to the proportion mentioned in the preparation example 3, granulating, and tabletting to obtain the preparation example 3-a control tablet.

Mixing celery powder separately according to the proportion mentioned in preparation example 3, granulating and tabletting to obtain preparation example 3-1 celery separate fermentation and tabletting; and (3) mixing the rhizoma polygonati extracts separately according to the proportion mentioned in the preparation example 3, granulating and tabletting to obtain the rhizoma polygonati single fermentation and tabletting of the preparation example 3-2.

Preparation example 4 preparation of celery and polygonatum sibiricum enzyme tabletted candy

According to the invention, the preparation of the rhizoma polygonati extract in the celery rhizoma polygonati enzyme tabletting candy is realized by the following steps:

1) reflux-extracting rhizoma Polygonati decoction pieces with ethanol at a ratio of 1:9 for 1.5 hr and 80% ethanol concentration for 2 times, and collecting filtrate and residue respectively.

2) Extracting the filter residue after alcohol extraction in the step 1) with water according to the ratio of material to liquid of 1:16 for 1.5 hours, repeatedly extracting for 2 times, discarding the filter residue, and combining the filter residue with the alcohol extraction filtrate in the step 1) to obtain a mixed filtrate.

3) Concentrating the mixed filtrate in the step 2) under reduced pressure to obtain an extract with the relative density of 1.08, and performing spray drying to obtain the sealwort extract.

According to the celery and sealwort ferment tablet candy, the preparation method is realized through the following steps:

1) and (4) checking: harvesting fresh celery leaves, removing weeds, washing away impurities such as sludge by clear water, and using after the inspection is qualified.

2) And (3) disinfection: sterilizing the cleaned fresh celery leaves by using ultraviolet rays.

3) Cutting: cutting sterilized fresh celery leaves into 1cm wide.

4) Drying and crushing: freeze-drying the cut celery leaves in the step 3) and crushing into celery leaf powder.

5) Preparing a lactobacillus seed solution: inoculating-80 deg.C frozen Lactobacillus plantarum CGMCC8198 into certain amount of MRS culture medium with an inoculum size of 1%, and culturing in 32 deg.C anaerobic incubator until viable count reaches 10⁸cfu/mL, activated for 3 generations according to the method to obtain the lactobacillus seed solution.

6) Inoculation and fermentation: uniformly mixing 80 parts of celery powder obtained in the step 4) with 18 parts of rhizoma polygonati extract, 15 parts of inulin and 15 parts of corn starch, adding 6 times of water, uniformly mixing, inoculating the seed liquid obtained in the step 5) according to the amount of 32mL of seed liquid/L of mixed juice, and stirring and fermenting for 5 days at 38 ℃.

7) Primary homogenizing and filtering: homogenizing the fermentation product obtained after the fermentation in the step 6) under 45MPa, filtering, and removing insoluble substances in thallus residues to obtain filtrate.

8) Concentration and spray drying: and (4) concentrating the fermentation filtrate obtained in the step (7) under reduced pressure to obtain a concentrated solution with the relative density of 1.1, and performing spray drying on the concentrated solution to obtain the raw material powder before tabletting.

9) Uniformly mixing the raw material powder (100 parts) in the step 8) with 4 parts of calcium hydrophosphate and 1 part of magnesium stearate, granulating and tabletting to obtain the celery sealwort ferment tabletting candy 4 for subsequent efficacy tests.

The celery leaf powder in the step 4) is not detected to be apigenin by high performance liquid chromatography.

Detecting the apigenin content of 35mg/g by high performance liquid chromatography, detecting the polygonatum polysaccharide content of 420 mu g/g by phenol-sulfuric acid method, and detecting the polygonatum total flavone content of 155 mu g/g by spectrophotometry in the step 9).

Mixing the unfermented celery powder and the unfermented polygonatum extract according to the proportion mentioned in preparation example 4, granulating, and tabletting to obtain preparation example 4-control tablet.

Mixing celery powder separately according to the proportion mentioned in preparation example 4, granulating and tabletting to obtain preparation example 4-1 celery separate fermentation and tabletting; the sealwort extract is separately mixed, granulated and tabletted according to the proportion mentioned in preparation example 3 to obtain preparation example 4-2 sealwort separately fermented and tabletted.

Preparation example 5 preparation of celery and sealwort enzyme tabletted candy

According to the invention, the preparation of the rhizoma polygonati extract in the celery rhizoma polygonati enzyme tabletting candy is realized by the following steps:

1) extracting rhizoma Polygonati decoction pieces with ethanol at a ratio of 1:10 under reflux for 2 hr, extracting with 75% ethanol for 2 times, and collecting filtrate and residue respectively.

2) Extracting the filter residue after alcohol extraction in the step 1) with water according to the ratio of material to liquid of 1:20 for 1.5 hours, repeatedly extracting for 2 times, discarding the filter residue, and combining the filter residue with the alcohol extraction filtrate in the step 1) to obtain a mixed filtrate.

3) Concentrating the mixed filtrate in the step 2) under reduced pressure to obtain an extract with the relative density of 1.15, and performing spray drying to obtain the sealwort extract.

According to the celery and sealwort ferment tablet candy, the preparation method is realized through the following steps:

1) and (4) checking: harvesting fresh celery leaves, removing weeds, washing away impurities such as sludge by clear water, and using after the inspection is qualified.

2) And (3) disinfection: sterilizing the cleaned fresh celery leaves by using ultraviolet rays.

3) Cutting: cutting sterilized fresh celery leaves into pieces with a width of 0.8 cm.

4) Drying and crushing: freeze-drying the cut celery leaves in the step 3) and crushing into celery leaf powder.

5) Preparing a lactobacillus seed solution: inoculating-80 deg.C frozen Lactobacillus plantarum CGMCC8198 into certain amount of MRS culture medium with an inoculum size of 1%, and culturing in 32 deg.C anaerobic incubator until viable count reaches 10⁸cfu/mL, activated for 3 generations according to the method to obtain the lactobacillus seed solution.

6) Inoculation and fermentation: uniformly mixing 70 parts of celery powder obtained in the step 4) with 15 parts of rhizoma polygonati extract, 15 parts of inulin and 10 parts of corn starch, adding 8 times of water, uniformly mixing, inoculating the seed liquid obtained in the step 5) according to the amount of 35mL of seed liquid/L of mixed juice, and stirring and fermenting for 5 days at 37 ℃.

7) Primary homogenizing and filtering: homogenizing the fermentation product obtained after fermentation in the step 6) under 50MPa, filtering, and removing insoluble substances in thallus residues to obtain filtrate.

8) Concentration and spray drying: and (4) concentrating the fermentation filtrate obtained in the step (7) under reduced pressure to obtain a concentrated solution with the relative density of 1.1, and performing spray drying on the concentrated solution to obtain the raw material powder before tabletting.

9) Uniformly mixing the raw material powder (100 parts) in the step 8) with 3 parts of calcium hydrophosphate and 1 part of magnesium stearate, granulating and tabletting to obtain the celery sealwort ferment tabletting candy 5 for subsequent efficacy tests.

The celery leaf powder in the step 4) is not detected to be apigenin by high performance liquid chromatography.

Detecting the apigenin content of 40mg/g by high performance liquid chromatography, detecting the polygonatum polysaccharide content of 440 mu g/g by phenol-sulfuric acid method, and detecting the polygonatum total flavone content of 175 mu g/g by spectrophotometry in the celery and polygonatum enzyme tabletting candy in the step 9).

Mixing the unfermented celery powder and the unfermented polygonatum extract according to the proportion mentioned in preparation example 5, granulating, and tabletting to obtain preparation example 5-control tablet.

The preparation conditions and the analysis results of preparation examples 1 to 5 are shown in the following tables.

TABLE 1 summary of the conditions and chemical analysis results of preparation examples 1-5

Test example 1 taking test of celery and sealwort enzyme tabletted candy

The celery and sealwort enzyme tabletting candies obtained in the embodiments 1-5 are subjected to taking tests, the unfermented celery powder and the unfermented sealwort extract are uniformly mixed, granulated and tabletted according to the proportion of each embodiment to obtain corresponding control tabletting, 300 hypertensive (high pressure is less than or equal to 160mmHg) volunteers are gathered, the groups are averagely divided into 10 groups, the trial amount is 9 tablets/person/day, and the taking period is 30 days.

The results of the administration test are statistically as follows:

before the test is started, the patient takes the conventional antihypertensive drug 2 times a day, and takes the antihypertensive drug once in the morning and at night, so that the blood pressure can be controlled within an ideal range. Within 10 days after the test, the product is taken three times in the morning, in the middle of the day and at night, and the regular antihypertensive drug is taken normally in the morning and 1 tablet is reduced in the evening after the 11 th day, so that the product is taken three times a day. The blood pressure control was measured at the 2 nd, 3 rd and 4 th weekends, and the blood pressure control was judged to be effective in the ideal range, and the results are shown in table 2.

TABLE 2 test results of taking celery and sealwort enzyme tabletted candies

Table 2 shows that the product has the effect of assisting in reducing blood pressure, the dosage of the chemical antihypertensive drug can be reduced by reasonably using the product, and the antihypertensive effect of the product is obviously superior to that before fermentation after the product is transformed by a special fermentation technology.

In addition, aiming at preparation examples 3 and 4, separate celery and sealwort fermentation groups are respectively arranged, namely one group is only fermented by celery (3-1 and 4-1), the other group is only fermented by sealwort (3-2 and 4-2), the rest materials are uniformly mixed according to the proportion of the corresponding example, granulated and tabletted to obtain a control tablet, and whether the two have the synergistic effect is evaluated. 180 volunteers with hypertension (the high pressure is less than or equal to 160mmHg) are collected, the groups are averagely divided into 6 groups, the trial amount is 9 tablets/person/day, and the trial period is 30 days.

The statistics of the trial results are as follows:

before the test is started, the patient takes the conventional antihypertensive drug 2 times a day, and takes the antihypertensive drug once in the morning and at night, so that the blood pressure can be controlled within an ideal range. Within 10 days after the test, the product is taken three times in the morning, in the middle of the day and at night, and the regular antihypertensive drug is taken normally in the morning and 1 tablet is reduced in the evening after the 11 th day, so that the product is taken three times a day. Measuring blood pressure control conditions at the 2 nd, 3 rd and 4 th weeks respectively, judging the blood pressure control to be effective in an ideal range, simultaneously respectively calculating the interaction index CI of the combined fermentation of the celery and the rhizoma polygonati as AB/(A multiplied by B), T is the total number of examples of each group, C is the effective number of examples of each group in different time periods, AB is the value of (T-C)/T used for the combined fermentation of the two raw materials, and A, B is the value of (T-C)/T used for the single fermentation action groups of the celery and the rhizoma polygonati. When CI is less than 1, the two raw materials have synergistic effect when combined for fermentation, and when CI is less than or equal to 0.7, the synergistic effect is very obvious, and the results are recorded in Table 3.

TABLE 3 test results of celery and sealwort enzyme tabletted candies

As can be seen from Table 3, the combined antihypertensive effect of celery and polygonatum is better than that of the single effect, and the CI index shows that the combination of celery and polygonatum has obvious synergistic effect.

Test example 2 celery and sealwort enzyme tabletted candy taking test

The celery and sealwort enzyme tabletting candies obtained in the preparation examples 1-5 are subjected to taking tests, meanwhile, the unfermented celery powder and the unfermented sealwort extract are uniformly mixed, granulated and tabletted according to the proportion of each example to obtain corresponding control tabletting, 300 volunteers with hypertension (160mmHg is less than or equal to high pressure and less than or equal to 190mmHg) are gathered, the concurrent symptoms such as headache and dizziness are accompanied, the average group is 10, the trial amount is 9 tablets/person/day, and the taking period is 30 days.

The results of the administration test are statistically as follows: before the test is started, the patient takes the conventional antihypertensive drug 2 times a day, and takes the antihypertensive drug once in the morning and at night, so that the blood pressure can be controlled within an ideal range. Within 10 days after the test, the product is taken three times in the morning, in the middle of the day and at night, and the regular antihypertensive drug is taken normally in the morning and 1 tablet is reduced in the evening after the 11 th day, so that the product is taken three times a day. Blood pressure control was measured at the end of 2, 3 and 4 weeks, respectively, and blood pressure control was within the ideal range and reduction of headache and dizziness was judged to be effective, and the results are shown in table 4.

TABLE 4 test results of taking celery and sealwort enzyme tabletted candies

Table 4 shows that the product has the auxiliary effect of lowering blood pressure, can simultaneously relieve symptoms such as headache, dizziness and the like caused by hypertension, and has the treatment effect remarkably superior to that before fermentation after the conversion of a special fermentation technology, so that the use amount of chemical antihypertensive drugs can be reduced by reasonably using the product.

In addition, aiming at preparation examples 3 and 4, separate celery and sealwort fermentation groups are respectively arranged, namely one group is only fermented by celery (3-1 and 4-1), the other group is only fermented by sealwort (3-2 and 4-2), the rest materials are uniformly mixed according to the proportion of the corresponding example, granulated and tabletted to obtain a control tablet, and whether the two have the synergistic effect is evaluated. 180 volunteers with hypertension (the high pressure is more than or equal to 160mmHg and less than or equal to 190mmHg) are gathered together, the volunteers are accompanied with the complicating symptoms of headache, dizziness and the like, the groups are averagely divided into 6 groups, the trial amount is 9 tablets/person/day, and the trial period is 30 days.

The statistics of the trial results are as follows:

before the test is started, the patient takes the conventional antihypertensive drug 2 times a day, and takes the antihypertensive drug once in the morning and at night, so that the blood pressure can be controlled within an ideal range. Within 10 days after the test, the product is taken three times in the morning, in the middle of the day and at night, and the regular antihypertensive drug is taken normally in the morning and 1 tablet is reduced in the evening after the 11 th day, so that the product is taken three times a day. Measuring blood pressure control conditions at the end of 2 weeks, 3 weeks and 4 weeks respectively, judging that the blood pressure control is in an ideal range and the headache and dizziness symptoms are relieved, simultaneously respectively calculating the interaction index CI of the combined fermentation of the celery and the polygonatum sibiricum as AB/(A multiplied by B), T is the total number of cases of each group, C is the number of effective cases of each group which tries different time periods, AB is the value of (T-C)/T of the combined fermentation of the two raw materials, and A, B is the value of (T-C)/T of the single fermentation group of the celery and the polygonatum sibiricum. When CI is less than 1, the two raw materials have synergistic effect when combined fermentation, and when CI is less than or equal to 0.7, the synergistic effect is very obvious. The results are reported in table 5.

TABLE 5 test results of taking celery, sealwort and enzyme tablet candy

As can be seen from Table 5, the combined antihypertensive effect of celery and polygonatum and the effect of relieving the hypertension complications are better than the single effect, and the CI index shows that the combination of celery and polygonatum has an obvious synergistic effect.

Test example 3 animal experiment of celery and sealwort enzyme tabletted candy for lowering blood pressure

According to the crowd trial results of the test examples 1 and 2, the composition in the preparation example 4 (without granulation and tabletting) is selected for carrying out a blood pressure reduction animal experiment, meanwhile, celery and sealwort separate fermentation groups (4-1 and 4-2) are arranged, and the rest materials are uniformly mixed according to the proportion of the example 4 (without granulation and tabletting), and the test method and the results are as follows:

1. materials and methods

1.1 sample sources: prepared by fermentation in example 4, and is divided into a celery plus sealwort fermentation group, a celery fermentation group (4-1) and a sealwort fermentation group (4-2).

1.2 Experimental animals: SHR rats, male, SPF grade, body weight 210-230 g, Beijing Wintolite laboratory animal technology GmbH.

1.3 Experimental reagents: pentobarbital sodium reagent was purchased from sigma, usa.

1.4 Experimental instruments: a non-invasive blood pressure measuring system (MD3000), a pipette (Eppendorf), an electronic balance (ME104E), a syringe, a gavage needle, a surgical instrument, an AngII enzyme-linked immunosorbent assay (ELISA) assay kit (R & D company), and an IL-10 enzyme-linked immunosorbent assay (ELISA) assay kit (R & D company).

2. Experimental methods

2.1 Experimental groups and dosages

The experimental animals are shown in 1.2, and each 6 rats are 1 group, and the total number of the groups is 4. Three test groups, namely a celery + rhizoma polygonati fermentation group, a celery fermentation group and a rhizoma polygonati fermentation group are arranged, and the specific dosage is as follows: a celery and rhizoma polygonati fermentation group: apigenin 35mg/kg bw, rhizoma Polygonati polysaccharide 420 μ g/kg bw, rhizoma Polygonati flavone content 155 μ g/kg bw; ② celery fermentation group: apigenin 35mg/kg · bw; ③ rhizoma polygonati fermentation group: 420 mug/kg bw of polygonatum polysaccharide and 155 mug/kg bw of polygonatum flavone. A model control group was also set. Respectively feeding the animals with the corresponding dose groups into the stomach, wherein the stomach filling volume is 0.2mL/10gbw, and feeding the blank solution with the same volume into the model control group, wherein the stomach filling is carried out once a day for 30 days continuously.

2.2 detection index and method

The administration is carried out 1 time per day for 4 weeks, and the Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) of each group of rats are measured and recorded by a non-invasive blood pressure measuring system before the experiment and every two weeks after the administration.

After the experiment is finished, injecting pentobarbital sodium into an abdominal cavity to anaesthetize a rat, taking blood from an abdominal aorta, standing, centrifuging and separating serum, preserving at-80 ℃, detecting the AngII level and IL-10 serology, rapidly picking the heart, weighing the body mass of each group of rats, taking the heart and weighing, stripping the left ventricle and weighing, and calculating a heart coefficient CWI and a left ventricle hypertrophy index MPI: CWI ═ mass of core/mass of body × 100%, MPI ═ mass of left ventricle/mass of core × 100%.

3. Results and analysis

3.1 Effect of different compositions on SBP of SHR rats

SBP of SHR rats is measured before and every two weeks after the experiment, and the blood pressure reduction rate of the whole administration period is calculated as (initial blood pressure value-final blood pressure value)/initial blood pressure value multiplied by 100%, and the interaction index CI of the combined fermentation of the celery and the rhizoma polygonati is AB/(A multiplied by B), T is the final blood pressure of a model control group, C is the final blood pressure value of each group, AB is the C/T value of the combined fermentation of the two raw materials, and A, B is the C/T value of the single fermentation action group of the celery and the rhizoma polygonati. When CI is less than 1, the two raw materials are combined to have synergistic effect, when CI is less than or equal to 0.7, the synergistic effect is very obvious, and the results are recorded in Table 6.

TABLE 6 Effect of different groups on SBP of SHR rats

As can be seen from Table 6, before the tested composition is administered, the SBP of the experimental animals of each group of SHR has no significant difference (P >0.05), when the rats are orally administered with different composition dry powder for 30d, the SBP of the rats of each group is lower than that of the model control group, the difference between the celery + rhizoma polygonati fermentation group and the model control group has significant value (P <0.05), which indicates that celery and rhizoma polygonati have the function of reducing blood pressure after fermentation, and the CI index shows that the combination of the celery and the rhizoma polygonati has the synergistic effect.

3.2 Effect of different compositions on DBP in SHR rats

DBP of SHR rats is measured before an experiment and every two weeks after administration, the blood pressure reduction rate of the whole administration period is calculated as (initial blood pressure value-final blood pressure value)/initial blood pressure value multiplied by 100%, the interaction index CI of the combined fermentation of the celery and the sealwort is calculated as AB/(A multiplied by B), T is the final blood pressure of a model control group, C is the final blood pressure value of each group, AB is the C/T value of the combined fermentation of the two raw materials, and A, B is the C/T value of the single fermentation action group of the celery and the sealwort. When CI is less than 1, the two raw materials have synergistic effect when combined for fermentation, and when CI is less than or equal to 0.7, the synergistic effect is very obvious, and the results are recorded in Table 7.

TABLE 7 Effect of different compositions on DBP of SHR rats

As can be seen from Table 7, before the tested composition is administered, the DBP of each group of experimental animals of the SHR has no significant difference (P >0.05), when the rats are orally administered with different composition dry powders for 30d, the DBP of each group of rats is lower than that of the model control group, and the difference between the celery + rhizoma polygonati fermentation group and the model control group has significance (P <0.05), which indicates that celery and rhizoma polygonati have the function of reducing blood pressure after fermentation, and the CI index indicates that the combination of the celery and the rhizoma polygonati has the synergistic effect.

3.3 Effect of different compositions on CWI and MPI in SHR rats

At the end of the test, weighing the body mass of rats in each group, taking and weighing hearts, peeling off the left ventricle and weighing, calculating CWI and MPI values, calculating the interaction index CI of the combined fermentation of the two raw materials of celery and rhizoma polygonati as AB/(A multiplied by B), T being the final CWI and MPI of the model control group, C being the final CWI and MPI of each group, AB being the C/T value of the combined fermentation of the two raw materials, and A, B being the C/T value of the single fermentation action group of celery and rhizoma polygonati. When CI is less than 1, the two raw materials have synergistic effect when combined for fermentation, and when CI is less than or equal to 0.7, the synergistic effect is very obvious, and the results are recorded in Table 8.

TABLE 8 Effect of different compositions on CWI and MPI in SHR rats

From table 8, after the rats are orally administered with different compositions of dry powder for 30 days, the CWI and MPI values of the rats in each group are lower than those of the model control group, and the difference between the celery plus rhizoma polygonati fermentation group and the model control group is significant (P is less than 0.05), which indicates that the celery and the rhizoma polygonati fermentation group have the effect of reducing the heart coefficient and the left ventricular hypertrophy index, and the two indexes, namely CI indexes, show that the combination of the celery and the rhizoma polygonati has the synergistic effect.

3.4 Effect of different compositions on serum AngII levels in SHR rats

At the end of the assay, the levels of AngII and IL-10 in rat serum were measured using an AngII enzyme-linked immunosorbent assay (ELISA) kit and an IL-10 enzyme-linked immunosorbent assay (ELISA) kit, and the results are reported in Table 9.

TABLE 9 Effect of different compositions on AngII levels and IL-10 levels in SHR rats

As can be seen from table 9, after the rats were orally administered with different compositions of dry powder for 30 days, the AngII water average of each group of rats was lower than that of the model control group, and the differences between the celery + polygonatum rhizome fermentation group and the celery fermentation group and the model control group were significant (P <0.05), indicating that apigenin regulates and controls blood pressure by regulating the renin-angiotensin system (RAS) of the body, supposing that apigenin may inhibit the activity of Angiotensin Converting Enzyme (ACE), and reduce the conversion of ACE to AngI and further reduce the AngII level; the IL-10 of rats in each group has higher water average value than that of a model control group, and the differences between the celery + rhizoma polygonati fermentation group and the model control group have significance (P is less than 0.05), which indicates that rhizoma polygonati flavone and polysaccharide play a role in reducing blood pressure by regulating the immune function of an organism, and researches show that most of patients with hypertension have immune dysfunction, mainly reflect the cell immune dysfunction, so that the cell immune dysfunction is deduced to be one of the pathogenesis of hypertension, and the IL-10 has the function of stopping inflammatory reaction, can inhibit inflammatory cells from generating various inflammatory factors such as IL-1 and the like, reduce inflammatory injury and play a role in protecting vascular endothelium and heart.

While embodiments of the present invention have been described above, the present invention is not limited to the specific embodiments and applications described above, which are intended to be illustrative, instructive, and not limiting. Those skilled in the art, having the benefit of this disclosure, may effect numerous modifications thereto without departing from the scope of the invention as defined by the appended claims.