A method suitable for industrial production of curcumin crystals

Abstract

The invention provides a method suitable for industrial production of curcumin crystals, the method comprising: first extracting turmeric particles with ethyl acetate to obtain a turmeric crude extract, mixing the turmeric crude extract with an impurity remover, separating, concentrating the upper solvent under reduced pressure to obtain turmeric oil, concentrating the middle impurity layer under reduced pressure to obtain a polysaccharide substance, concentrating the lower layer under reduced pressure to obtain a turmeric extract, dissolving the turmeric extract in ethanol, removing the solvent, refining and drying to obtain a curcumin crystal with a purity higher than 96%, a residual solvent lower than 1000ppm, and a content yield higher than 83%. The process flow of the invention is short, there is no risk of adding an emulsifier and an acid-base substance, and secondary crystallization is not required. The obtained curcumin crystal product has a high content, and does not contain organic solvents harmful to the human body such as acetonitrile. The method of the invention is simple to operate, low in cost, and easy to control, and is suitable for industrial production.

Description

Technical Field

[0001] The invention relates to the technical field of plant extraction, and in particular to a method suitable for industrial production of curcumin crystals. Background Art

[0002] Turmeric is a perennial herb of the genus Curcuma in the Zingiberaceae family. It has well-developed rhizomes, which form clusters and have oval or cylindrical branches. It contains a variety of chemical components and has good medicinal value and economic prospects. Curcuminoids are the main active ingredients of turmeric. They are diphenylheptane substances, yellow in color, with a special aroma, slightly acidic, and lipophilic. Curcuminoids not only have bright colors, strong coloring power, and good color retention, and are widely used in the field of food and cosmetics as colorants, but also have high thermal stability and rich biological activities such as antibacterial, anti-inflammatory, and anti-cancer. They are widely used in the medical field to play a role in nutrition and health care, and have good development prospects.

[0003] At present, the curcumin produced in China for export strictly complies with the USP40 standard, which requires the curcumin content to be greater than 96% and the residual content to be less than 5000ppm. However, in the actual production process of curcumin, unqualified curcumin often appears, which seriously affects product sales and economic benefits. Therefore, it is necessary to improve the production rate and increase economic benefits as much as possible while ensuring product quality.

[0004] CN110724045A achieves curcumin crystallization by strict control of the curcumin crystallization procedure and related parameters, and achieves curcumin crystallization in the form of adding seed crystals, thereby obtaining curcumin with high purity and residual solvent less than 10ppm. However, in the actual extract concentration process, strict crystallization procedure and parameter control are extremely dependent on precise equipment, and it is difficult to achieve a 100% success rate, and the investment cost is high. CN107805193A promotes the removal of solvent residues in turmeric extract by adding propylene glycol, Tween 80 and other additives, thereby obtaining curcumin with a content higher than 95% and residual solvent less than 10ppm. However, more processing aids are used in this process, which increases costs and is difficult to remove. There is a risk of introducing these additives into the final product, which will also affect the yield. CN113264817A uses acetone to extract turmeric raw materials, removes part of the solvent and then adds acetonitrile to dissolve, cools and crystallizes under mixed solvent conditions, grows crystals, and obtains curcumin with a purity of more than 99% and a solvent residue of less than 50ppm after filtration. However, the method has a low extraction yield with acetone, and the toxicity of the mixed solvent of acetone and acetonitrile is strong, which is not suitable for large-scale production. Even if the residue is less than 50ppm, there is a high risk of acetonitrile introduction. CN103130629A uses turmeric raw materials for acid-base extraction to obtain a curcumin product with a content of ≥95% and a yield of ≥80%, but the curcumin extracted by alkaline water loses quickly, and the output curcumin is unstable.

[0005] Therefore, the production and processing of curcumin urgently requires a production method that can promote the crystallization of curcumin and reduce residual solubility, which requires simple operation, low cost and suitable for industrial production. Summary of the invention

[0006] In view of the shortcomings of the prior art, the present invention provides a method suitable for industrial production of curcumin crystals, which is conducive to obtaining curcumin crystals with high purity and low residual solvent, and the residual solvent has little harm, and can be applied to food additives and medicines.

[0007] In a first aspect, the present invention provides a method suitable for industrial production of curcumin crystals, comprising the following steps:

[0008] (1) extracting turmeric granules with ethyl acetate to obtain a turmeric crude extract;

[0009] (2) mixing the turmeric crude extract with an impurity remover, standing and separating, concentrating the upper layer solvent under reduced pressure to obtain turmeric oil, concentrating the middle impurity layer under reduced pressure to obtain polysaccharide substances, and concentrating the lower layer under reduced pressure to obtain turmeric extract;

[0010] (3) dissolving the turmeric extract in ethanol, removing the solvent, refining and drying to obtain curcumin crystals with a purity higher than 96%, a residual solvent lower than 1000 ppm, and a content yield higher than 83%.

[0011] Curcumin crystals are generally obtained by crystallizing a crude turmeric extract extracted from turmeric, but impurities related to the structure of curcumin that do not participate in the reaction are difficult to be completely removed by crystallization, which will affect the purity of the curcumin crystals. The present invention removes impurities from the crude turmeric extract to reduce the impurity content in the crystallization process, and the turmeric extract after impurity removal is subjected to solvent replacement to improve the crystal purity. The two methods simultaneously improve the crystallinity, enhance the tightness between curcumin molecules, and reduce the residual content. The obtained curcumin crystal product has high purity, a unit content of more than 96%, a residual content of less than 1000ppm, a content yield of more than 83%, and the method does not use organic reagents such as acetonitrile that are harmful to the human body. The method of the present invention is simple to operate, low in cost, and easy to control, and is suitable for industrial production.

[0012] In some embodiments of the present invention, in step (1), the residual solvent of the turmeric crude extract is ≤25000 ppm. After extraction with ethyl acetate, the solvent is generally concentrated and removed. The obtained turmeric crude extract is semi-solid and can flow when heated, but has poor fluidity without heating.

[0013] In some embodiments of the present invention, in step (2), the impurity remover is a mixed solvent of an aqueous solvent and petroleum ether, the mixing ratio of the aqueous solvent to the petroleum ether is 20-50:50-80 (V / V), the aqueous solvent is any one of aqueous acetone, aqueous methanol, and aqueous ethanol; the solvent volume purity of the aqueous solvent is 20%-90%.

[0014] In some embodiments of the present invention, in step (2), the solid-liquid ratio of the turmeric crude extract to the impurity remover is 1:1.2-2.5 (w / v), the mixing temperature is 40-65° C., the mixing and stirring time is 15-60 minutes, and the standing separation time is 60-90 minutes.

[0015] In some embodiments of the present invention, in step (3), the purity of the ethanol is 90-100%, and the solid-liquid ratio of the turmeric extract to the ethanol is 1:0.05-0.2 (w / v).

[0016] In some embodiments of the present invention, in step (3), in the step of dissolving the turmeric extract in ethanol, the temperature is set to 80-90°C.

[0017] In some embodiments of the present invention, in step (3), the solvent is removed by concentrating under reduced pressure at a temperature of 65-90° C. and a vacuum degree of -0.080 to -0.095 MPa until no solvent flows out.

[0018] In some embodiments of the present invention, in step (3), the refining comprises:

[0019] Any one of a mixed solvent of alkanes and ethanol, a mixed solvent of alkanes and ethyl acetate, and a mixed solvent of alkanes and isopropanol in a volume ratio of 4:6-9 is used as a refining solvent, and the solid product obtained by removing the solvent is dissolved in the refining solvent at 50-65° C., and the filter residue is filtered out; wherein the purity of ethanol, ethyl acetate, and isopropanol is ≥98.0%.

[0020] Preferably, the addition amount of the refined solvent is 50%-90% (v / w) of the solid product, the stirring speed during the dissolution process is 150-250 r / min, and the stirring time is 3-5 h.

[0021] Before refining, the purity of curcumin is about 32% to 37%. After refining, curcumin with a purity higher than 96% can be obtained.

[0022] In some embodiments of the present invention, the method for industrial production of curcumin crystals comprises the following steps:

[0023] The turmeric particles are extracted with an organic solvent to obtain a turmeric crude extract, the turmeric crude extract is mixed with an impurity remover, the lower layer is concentrated under reduced pressure after solid-liquid separation to obtain a turmeric extract, ethanol is added to the turmeric extract and stirred in a water bath at 80-90°C, and after dissolution, it is concentrated under reduced pressure until there is no solvent, and after one-time refining and drying, curcumin crystals with a purity higher than 96% and a residual solution lower than 1000 ppm are obtained, and the content yield is greater than 83%.

[0024] In some embodiments of the present invention, the filter residue is dried to obtain curcumin crystals, wherein the drying temperature is 90-105° C. and the drying time is 3-9 h.

[0025] In a second aspect, the present invention provides a curcumin crystal, which is prepared by any of the above methods, wherein the purity of the curcumin crystal is higher than 96%, the content yield is greater than 83%, the total amount of residual solution in the curcumin crystal is less than 1000 ppm and does not contain acetonitrile.

[0026] In a specific embodiment of the present invention, the residual solvent in the curcumin crystals is mainly ethyl acetate, n-hexane and ethanol. If acetone is used, the residual solvent in acetone is not higher than 10 ppm.

[0027] The present invention also provides application of the curcumin crystals in food additives and medicines.

[0028] Curcumin is widely used in the food industry as a condiment and pigment at home and abroad, and is mainly used for dyeing canned food, sausage products, and marinated products. The curcumin crystals obtained by the present invention can be directly applied to food and medicine, or processed into other forms and then added for application, and the amount added is added according to the allowable amount specified in relevant laws and regulations.

[0029] The invention provides a method suitable for industrial production of curcumin crystals. The impurity content of the crystallization process is reduced by removing impurities from a turmeric crude extract, and the crystal purity can be improved by solvent replacement of the turmeric extract after impurities removal. The two methods simultaneously improve the crystallinity, enhance the compactness between curcumin molecules, and reduce the residual content. The obtained curcumin crystal product has high purity, a unit content of more than 96%, a residual content of less than 1000 ppm, a content yield of more than 83%, and the method does not use organic reagents such as acetonitrile that are harmful to the human body. The method of the invention is simple to operate, low in cost, easy to control, and suitable for industrial production. DETAILED DESCRIPTION

[0030] In order to make the purpose, technical solution and advantages of the present invention clearer, the technical solution of the present invention will be described clearly and completely below. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0031] The experimental methods used in the following examples are conventional methods unless otherwise specified. The materials, reagents, etc. used in the following examples are commercially available or prepared according to conventional methods in the art unless otherwise specified.

[0032] In the following examples, the purity detection method of curcumin crystals refers to the liquid phase detection method specified in the United States Pharmacopoeia USP39 Curcumin, and the solvent residue detection method refers to the solvent residue detection method specified in the GB1886.60-2015 National Food Safety Standard Food Additives-Turmeric.

[0033] Example 1

[0034] This embodiment provides a method suitable for industrial production of curcumin crystals, the steps of which are as follows:

[0035] (1) Turmeric granules were extracted with ethyl acetate to obtain a crude turmeric extract with a residual content of 18936 ppm;

[0036] (2) 116.42 g of turmeric crude extract was taken, stirred with 144 ml of a mixed solvent of n-hexane: 30% ethanol aqueous solution = 72:28 at 58° C. for 20 min, allowed to stand for 60 min, and the upper layer was concentrated under reduced pressure to obtain 37.82 g of turmeric oil;

[0037] (3) After separation, the middle impurity layer and the lower layer were vacuum deodorized at 85°C and -0.095 MPa for 2 h to obtain 4.8 g of polysaccharide and 73.8 g of turmeric extract, respectively;

[0038] (4) 7.4 ml of anhydrous ethanol was added to 73.8 g of turmeric extract and stirred at 80° C. for 1 h. The mixture was vacuum deodorized at 85° C. and -0.095 MPa for 2 h until there was no solvent. Then 60.6 ml of n-hexane:ethyl acetate = 4:7 (v / v) refining solvent was added. The mixture was stirred and refined at 60° C. for 3 h. The mixture was filtered and the residue was dried at 105° C. for 3 h to obtain 34.73 g of curcumin crystals.

[0039] After testing, the unit content of the obtained curcumin crystals, i.e., purity, was 98.56%, the content yield was 84.8%, and the total solvent residue (ethyl acetate 762ppm, n-hexane 38ppm, ethanol 29ppm) was 829ppm. Wherein, the content yield = (curcumin crystal purity 98.56% * weight 34.73g) / (turmeric crude extract content 34.68% or so * weight 116.42g) = 84.8%.

[0040] Example 2

[0041] This embodiment provides a method suitable for industrial production of curcumin crystals, the steps of which are as follows:

[0042] (1) Turmeric granules were extracted with ethyl acetate to obtain a crude turmeric extract with a residual solvent of 17366 ppm;

[0043] (2) 79.7 g of turmeric crude extract was taken, stirred with 120 ml of a mixed solvent of n-hexane:50% ethanol aqueous solution = 72:28 at 63° C. for 15 min, allowed to stand for 80 min, and the upper layer was concentrated under reduced pressure to obtain 39.74 g of turmeric oil;

[0044] (3) After separation, the middle impurity layer and the lower layer were vacuum deodorized at 85°C and -0.095 MPa for 4 h to obtain 3.6 g of polysaccharide and 36.36 g of turmeric extract, respectively;

[0045] (4) 3.6 ml of anhydrous ethanol was added to 36.36 g of turmeric extract and stirred at 80° C. for 1 h. The mixture was vacuum deodorized at 85° C. and -0.095 MPa for 4 h until there was no solvent. Then 47.82 ml of a refining solvent of n-hexane:ethanol = 4:8 (v / v) was added. The mixture was stirred and refined at 60° C. for 5 h. The mixture was filtered and the residue was dried at 95° C. for 5 h to obtain 23.82 g of curcumin crystals.

[0046] After testing, the unit content of the obtained curcumin crystals, i.e., the purity, was 99.56%, the content yield was 85.4%, and the total residual solvent (ethyl acetate 428 ppm, n-hexane 36 ppm, ethanol 10 ppm) was 474 ppm.

[0047] Example 3

[0048] This embodiment provides a method suitable for industrial production of curcumin crystals, the steps of which are as follows:

[0049] (1) Turmeric granules were extracted with ethyl acetate to obtain a crude turmeric extract with a residual content of 15378 ppm.

[0050] (2) 115.88 g of turmeric crude extract was taken and stirred with 140 ml of n-hexane:40% acetone = 80:20 at 50° C. for 30 min, allowed to stand for 60 min, and the upper layer was concentrated under reduced pressure to obtain 34.88 g of turmeric oil;

[0051] (3) After separation, the middle impurity layer and the lower layer were vacuum deodorized at 85°C and -0.095 MPa for 4 h to obtain 5.2 g of polysaccharide and 75.8 g of turmeric extract, respectively;

[0052] (4) 7.4 ml of anhydrous ethanol was added to 75.8 g of turmeric extract and stirred at 70° C. for 1 h. The mixture was vacuum deodorized at 85° C. and -0.095 MPa for 2 h until there was no solvent. Then 63.6 ml of n-hexane:ethyl acetate = 4:9 (v / v) refining solvent was added. The mixture was stirred and refined at 60° C. for 3 h. The mixture was filtered and the residue was dried at 105° C. for 3 h to obtain 35.38 g of curcumin crystals.

[0053] After testing, the unit content of the obtained curcumin crystals was 96.4%, the content yield was 84.1%, and the total residual (ethyl acetate 763ppm, n-hexane 36ppm, ethanol 48ppm, acetone 10ppm) was 857ppm.

[0054] Example 4

[0055] This embodiment provides a method suitable for industrial production of curcumin crystals, the steps of which are as follows:

[0056] (1) Turmeric granules were extracted with ethyl acetate to obtain a crude turmeric extract with a residual content of 13936 ppm.

[0057] (2) 159.28 g of turmeric crude extract was taken, stirred with 220 ml of a mixed solvent of n-hexane:60% methanol = 78:22 at 48°C for 20 min, allowed to stand for 60 min, and the upper layer was concentrated under reduced pressure to obtain 31.78 g of turmeric oil;

[0058] (3) After separation, the middle impurity layer and the lower layer were vacuum deodorized at 85°C and -0.095 MPa for 4 h to obtain 7.5 g of polysaccharide and 120 g of turmeric extract, respectively;

[0059] (4) 12 ml of anhydrous ethanol was added to 120 g of turmeric extract and stirred at 85° C. for 1.5 h. The mixture was vacuum deodorized at 85° C. and -0.095 MPa for 3 h until there was no solvent. Then 96 ml of n-hexane: ethyl alcohol = 4:7 (v / v) was added as a refining solvent. The mixture was stirred and refined at 65° C. for 4 h. The mixture was filtered and the residue was dried at 105° C. for 4 h to obtain 49.34 g of curcumin crystals.

[0060] After testing, the unit content of the obtained curcumin crystals, i.e., the purity, was 97.63%, the content yield was 86.4%, and the total residual solvent (ethyl acetate 642 ppm, n-hexane 43 ppm, ethanol 28 ppm, methanol 45 ppm) was 758 ppm.

[0061] Comparative Example 1

[0062] This comparative example provides a method for preparing curcumin crystals, the steps are as follows:

[0063] (1) Turmeric granules were extracted with ethyl acetate to obtain a crude turmeric extract with a residual solvent of 28986 ppm;

[0064] (2) 40 ml of ethanol was added to 50 g of turmeric crude extract for crystallization, and the mixture was stirred and purified at 65° C. for 4 h. The mixture was filtered and the residue was dried at 105° C. for 4 h to obtain 13.22 g of curcumin crystals.

[0065] After testing, the unit content of the obtained curcumin crystals, i.e., the purity, was 99.63%, the total residual solvent (ethyl acetate 636 ppm, ethanol 1027 ppm) was 1663 ppm, and the content yield was 71.2%.

[0066] Comparative Example 2

[0067] This comparative example provides a method for preparing curcumin crystals, the steps are as follows:

[0068] (1) Turmeric granules were extracted with ethyl acetate to obtain a crude turmeric extract with a residual solvent of 25973 ppm;

[0069] (2) 80.54 g of turmeric crude extract was stirred with 120 ml of a mixed solvent of n-hexane:ethanol = 82:18 at 48°C for 20 min, allowed to stand for 60 min, and the upper layer was concentrated under reduced pressure to obtain 35.64 g of turmeric oil;

[0070] (3) The lower layer was deodorized at 85°C and -0.095 MPa in a vacuum oven for 2 h to obtain 44.9 g of turmeric extract;

[0071] (4) 48 ml of n-hexane:ethanol = 4:7 (v / v) refining solvent was added to 44.9 g of turmeric extract, and the mixture was stirred and refined at 65° C. for 4 h. The mixture was filtered and the residue was dried at 105° C. for 4 h to obtain 23.9 g of curcumin crystals.

[0072] After testing, the unit content of the obtained curcumin crystals was 93.86%, the total solvent residue (ethyl acetate 1181 ppm, n-hexane 50 ppm, ethanol 27 ppm) was 1258 ppm, and the content yield was 75.3%.

[0073] Finally, it should be noted that the endpoints and any values ​​of the ranges disclosed in this article are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be regarded as specifically disclosed in this article.

[0074] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "specific implementations", or "some specific implementations" etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the embodiment of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, without contradiction.

[0075] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method suitable for industrial production of curcumin crystals, characterized in that, The following steps are involved: (1) extracting turmeric granules with ethyl acetate to obtain a crude turmeric extract; (2) mixing the turmeric crude extract with an impurity remover, standing and separating, concentrating the upper layer solvent under reduced pressure to obtain turmeric oil, concentrating the middle impurity layer under reduced pressure to obtain polysaccharide, and concentrating the lower layer under reduced pressure to obtain turmeric extract; The impurity remover is a mixed solvent of an aqueous solvent and n-hexane, the mixing ratio of the aqueous solvent to n-hexane is 20-50:50-80 V / V, the aqueous solvent is any one of aqueous acetone, aqueous methanol, and aqueous ethanol; the solvent volume purity of the aqueous solvent is 20%-90%; (3) dissolving the turmeric extract in ethanol, removing the solvent, refining and drying to obtain curcumin crystals with a purity higher than 96%, a residual solvent lower than 1000 ppm, and a content yield higher than 83%; The refining comprises: Any one of a mixed solvent of alkanes and ethanol, a mixed solvent of alkanes and ethyl acetate, and a mixed solvent of alkanes and isopropanol in a volume ratio of 4:6-9 is used as a refining solvent, and the solid product obtained by removing the solvent is dissolved in the refining solvent at 50-65° C., and the residue is filtered out.

2. The method according to claim 1, wherein the curcumin crystals are suitable for industrial production. In step (1), the residual content of the turmeric crude extract is ≤25000 ppm.

3. The method according to claim 1, wherein the curcumin crystals are suitable for industrial production. In step (2), the solid-liquid ratio of the turmeric crude extract to the impurity remover is 1:1.2-2.5 w / v, the mixing temperature is 40-65° C., the mixing and stirring time is 15-60 minutes, and the standing separation time is 60-90 minutes.

4. The method according to claim 1, wherein the curcumin crystals are suitable for industrial production. In step (3), the purity of the ethanol is 90-100%, and the solid-liquid ratio of the turmeric extract to the ethanol is 1:0.05-0.2 w / v.

5. The method according to claim 4, wherein the curcumin crystals are suitable for industrial production. In the step of dissolving the turmeric extract in ethanol, the temperature is set at 80-90°C.

6. The method suitable for industrial production of curcumin crystals according to any one of claims 1 to 5, characterized in that: In step (3), the solvent is removed by concentrating under reduced pressure at a temperature of 65-90° C. and a vacuum degree of -0.080 to -0.095 MPa until no solvent flows out.

7. The method suitable for industrial production of curcumin crystals according to any one of claims 1 to 5, characterized in that: In step (3), the amount of the refined solvent added is 50%-90% v / w of the solid product, the stirring speed during the dissolution process is 150-250 r / min, and the stirring time is 3-5 h.

8. The method according to claim 7, wherein: The filter residue is dried to obtain curcumin crystals, wherein the drying temperature is 90-105° C. and the drying time is 3-9 hours.