CN111728889A - A composition containing curcumin, ectoin and madecassoside with synergistic antiinflammatory effect, and its application - Google Patents
A composition containing curcumin, ectoin and madecassoside with synergistic antiinflammatory effect, and its application Download PDFInfo
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Abstract
The invention discloses a composition of curcumin, ectoin and madecassoside with synergistic anti-inflammatory effect and application thereof. The composition comprises the following components in percentage by weight: curcumin emulsion: ectoin: the madecassoside is 200-1:200-1:100-1, and the composition is preferably in a ratio of 10-1:200-1: 10-1. The curcumin, the ectoin and the madecassoside are combined to generate a synergistic effect, so that the curcumin, the ectoin and the madecassoside can be applied to the fields of cosmetics and skin surgery medicines for improving relevant inflammation such as skin redness, swelling, pruritus and allergy and skin barrier repair effects, experiments prove that the inhibition rate of the curcumin, the ectoin and the madecassoside composition on LPS (low lipid) induced NO can reach 66.33%, the synergistic index of the curcumin, the ectoin and the madecassoside is less than 1, and the curcumin, the ectoin and the madecassoside have remarkable synergistic anti-inflammatory and synergistic effects.
Description
Technical Field
The invention relates to the field of skin inflammation science, in particular to application of a synergistic anti-inflammatory and synergistic composition of curcumin, ectoin and madecassoside in daily cosmetics and skin surgery medicines for improving skin redness, itching, allergy, skin barrier repair effects and the like.
Background
The skin allergy and the inflammation of the human skin are common skin problems, sensitive or allergic skin is affected by external physical and chemical stimulation, pollen, hair scraps, air pollution, improper cosmetics use and other factors, and symptoms such as dry skin, redness, pruritus, desquamation, even burning, stabbing pain and the like are generated, and the generation mechanism of the skin allergy and the inflammation is mainly to stimulate the overexpression of skin-related inflammatory factors including TNF-alpha, IL-1 beta, IL-6, TGF-beta, IL-8, IL-10 and COX. At present, the anti-inflammatory active substance and the cosmetics thereof which are developed by adopting natural raw materials can be used for improving the problem of sensitive skin inflammation.
Ectoin (also called as tetrahydro-methyl pyrimidine carboxylic acid, Ectoin) is derived from a microbial extract in a high-temperature, high-salt and high-ultraviolet environment, is an amino acid derivative component, has a good repairing and protecting effect on skin, and is one of bioengineering preparations adopted by high-grade cosmetics. Research shows that the ectoin has the effects of delaying skin aging, preventing ultraviolet rays, resisting oxidation, preserving moisture, inhibiting inflammation and the like, can be applied to calming and relieving stimulated and damaged skin, remarkably increases the regeneration process of the skin, and is clinically even used for treating atopic dermatitis (neurodermatitis) or allergic skin diseases due to the excellent anti-inflammatory property of the ectoin. Chinese patent CN201810877933.7 takes ectoin as a raw material to prepare a skin-care substrate with the effects of moisturizing, improving wrinkles and resisting oxidation. The Chinese patent CN201910455035.7 takes glabridin and ectoin as raw materials to prepare the skin care composition, and has the efficacy of removing freckles and whitening.
The turmeric is a traditional Chinese medicine and a raw material with homology of medicine and food, contains curcumin, demethoxycurcumin, bisdemethoxycurcumin and other components, has the activities of resisting inflammation, bacteria, promoting wound healing, oxidation, tumor and the like, and the anti-inflammatory mechanism eliminates inflammatory reaction by inhibiting inflammatory factors such as NF-kappa B, VEGF, interleukin IL-1 beta, IL-6, IL-8 and the like. Turmeric is often used in indian folks as a traditional medicine for healing wounds and removing scars. Turmeric or curcumin are mainly used as pigments, anti-oxidation, antibacterial, whitening and freckle-removing agents in the fields of foods and cosmetics, and Chinese patent CN201110247893.6 adopts turmeric extract, blackberry lily extract and cherry plum extract to prepare a microemulsion matrix for whitening cosmetics for improving the whitening effect of the whitening cosmetics. The Chinese patent CNCN201110143774.6 takes turmeric extract as one of active raw materials to prepare a spot-removing composition for developing spot-removing whitening cosmetics. The skin inflammation of curcumin in the field of daily chemicals is not researched much, and the reason is that curcumin is poor in water solubility and poor in stability under the influence of factors such as illumination, pH value and metal ions, the currently adopted solubilizing agent is good in effect as a cationic surfactant, but the solubilizing agent is poor in compatibility with a cosmetic system, and application of solubilized curcumin in the field of cosmetics is limited.
Madecassoside is one of pentacyclic triterpenes active ingredients in centella asiatica of perennial herb of Umbelliferae, and research shows that Madecassoside has the functions of moisturizing, resisting oxidation, promoting wound healing and the like, and is mainly applied to treatment of skin wound, eczema, acne, hypertrophic scar, burn scar, scleroderma, psoriasis and other diseases. The madecassoside inhibits the translocation of TLR-2 and NF-kB, thereby inhibiting the skin inflammatory reaction caused by proinflammatory cytokine IL-1 beta (Shen X, Guo M, Yu H, et al bioscience Biotechnology & Biochemistry,2018,83(3): 1-8). The madecassoside has a plurality of hydroxyl groups and 3 glycosyl groups in the structure, has larger molecular weight and stronger polarity, cannot penetrate the horny layer of the skin epidermis, and limits the exertion of the efficacy, so the activity of the madecassoside on skin-related inflammation can be increased by cooperating the madecassoside with active ingredients of other small molecules to penetrate the horny layer of the skin and the like.
Disclosure of Invention
The curcumin emulsion, the ectoin and the madecassoside are used as raw materials, the curcumin emulsion has good dispersibility in a cosmetic system, and the curcumin emulsion, the ectoin and the madecassoside are reasonably compatible and combined based on the effects of the curcumin emulsion on skin inflammation, and the curcumin emulsion, the ectoin and the madecassoside are respectively regulated and controlled from inflammation pathway targets of a cuticle layer, a basal layer and a dermis layer of a skin epidermis to generate a synergistic effect. The compatibility of the three basic components further solves the problems of poor water solubility and stability of the curcumin and the technical defects of the curcumin in the application of the curcumin in the field of cosmetics, and the technical defect that the madecassoside cannot penetrate the cuticle of the epidermis of the skin to limit the exertion of the efficacy of the madecassoside. The synergistic anti-inflammatory composition of curcumin, ectoin and madecassoside is prepared, and efficacy experiments prove that the synergistic index of the combination of the curcumin, the ectoin and the madecassoside is less than 1, and the synergistic anti-inflammatory composition has obvious synergistic anti-inflammatory effect. The pharmaceutical and cosmetic acceptable dosage form is further prepared by selecting auxiliary materials allowed by pharmaceutical, food and cosmetic laws and regulations, and can be applied to the fields of cosmetics for improving skin-related inflammation and immune barrier repair and skin surgery medicines.
The above purpose of the invention is realized by the following technical scheme:
the composition of curcumin, ectoin and madecassoside with synergistic anti-inflammatory effect is prepared by the following preparation process steps:
s1, curcumin emulsification and dispersion: the curcumin emulsion comprises 5-12.5% of curcumin, 5-15% of hydrolyzed corn starch octenyl succinate, 0.5-5% of polyglycerol 10-laurate, 0.5-5% of glycerol stearate, 0.05% of caprylyl hydroximic acid, 0.5% of 1, 3-propylene glycol, 0.5% of 1, 2-hexanediol and the balance of water according to the weight of 100%;
s2, accurately weighing curcumin, hydrolyzed corn starch octenyl succinate, polyglycerol 10-laurate, glycerol stearate and water, mixing, and mechanically stirring at 3000r/min for 20min to obtain curcumin mixed solution;
s3, emulsifying and homogenizing: emulsifying the curcumin mixed solution obtained in the step S2 by adopting high-pressure homogenizing shearing for 0.5h-2.0h, wherein the homogenizing pressure is 10000-16000psi, and repeating for 2 times;
s4, adding capryl hydroximic acid, 1, 3-propylene glycol and 1, 2-hexanediol into the curcumin mixed solution obtained by homogenizing in the step S3, and uniformly stirring to obtain a curcumin emulsion;
s5, uniformly mixing the ectoin and the madecassoside with the curcumin emulsion prepared in the step S4 according to a proportion to obtain the curcumin, the ectoin and the madecassoside composition.
Preferably, the curcumin content in the curcumin emulsion is 8% -10%.
Preferably, the curcumin emulsion consists of the following components in percentage by weight: 8-10% of curcumin, 10-15% of hydrolyzed corn starch octenyl succinate, 0.5-1% of polyglycerol 10-laurate, 0.5-1% of glycerol stearate, 0.05% of caprylyl hydroximic acid, 0.5% of 1, 3-propylene glycol, 0.5% of 1, 2-hexanediol and the balance of water.
Compared with the prior art, the gain effect of the invention is as follows:
the invention prepares a composition of curcumin, ectoin and madecassoside with synergistic anti-inflammatory action through synergistic action, and solves the problems that curcumin, ectoin and madecassoside have poor water solubility and stability and the application of curcumin in the cosmetic field is limited by a solubilization technology while the effect of curcumin, ectoin and madecassoside on relevant skin inflammation is exerted, and the effect of madecassoside cannot penetrate the stratum corneum of the skin epidermis and the effect is limited by synergistic action of three active ingredients.
Furthermore, the invention does not simply combine ectoin with the curcumin emulsion, but the inflammation experiment proves that the synergy index of the curcumin, the ectoin and the madecassoside is less than 1, and the curcumin, the ectoin and the madecassoside have obvious synergistic anti-inflammatory and synergistic effects. The preparation method further comprises the step of selecting auxiliary materials allowed by food and cosmetic laws and regulations to prepare pharmaceutically and cosmetically acceptable dosage forms, and can be applied to the fields of cosmetics for improving skin-related inflammation and immune barrier repair and skin surgery medicines.
In addition, the composition of curcumin, ectoin and madecassoside with synergistic anti-inflammatory effect, provided by the invention, has a simple preparation process, and can be industrially popularized and applied.
Detailed Description
The present invention will be further described with reference to specific embodiments, but the present invention is not limited to the examples in any way. The starting reagents employed in the examples of the present invention are, unless otherwise specified, those that are conventionally purchased.
Example 1
A composition of curcumin, ectoin and madecassoside with synergistic anti-inflammatory action is prepared from ectoin and madecassoside 1:200:10, and curcumin in the emulsion (10%). The preparation method comprises the following preparation process steps:
s1, curcumin emulsification and dispersion: the curcumin emulsion comprises 10% of curcumin, 15% of hydrolyzed corn starch octenyl succinate, 1% of polyglycerol 10-laurate, 1% of glycerol stearate, 0.05% of caprylyl hydroximic acid, 0.5% of 1, 3-propylene glycol, 0.5% of 1, 2-hexanediol and the balance of water, wherein the curcumin emulsion is calculated by 100% by weight;
s2, weighing curcumin, hydrolyzed corn starch octenyl succinate, polyglycerol 10-laurate, glycerol stearate and water, and mixing, mechanically stirring at 3000r/min for 20min to obtain curcumin mixed solution;
s3, emulsifying and homogenizing: emulsifying the curcumin mixed solution obtained in the step S2 by adopting high-pressure homogenizing shearing for 2.0h, wherein the homogenizing pressure is 10000psi, and repeating for 2 times;
s4, respectively adding the rest caprylyl hydroximic acid, 1, 3-propylene glycol and 1, 2-hexanediol into the curcumin mixed solution obtained by homogenizing in the step S3, and uniformly stirring to obtain curcumin emulsion;
s5, uniformly mixing the ectoin and the madecassoside with the curcumin emulsion prepared in the step S4 according to a proportion to obtain the composition.
Example 2
A composition of curcumin, ectoin and madecassoside with synergistic anti-inflammatory action is prepared from ectoin and madecassoside 1:9:9, and curcumin in the emulsion (8%). The preparation method comprises the following preparation process steps:
s1, curcumin emulsification and dispersion: the curcumin emulsion comprises curcumin 8%, hydrolyzed corn starch octenyl succinate 10%, polyglycerol 10-laurate 0.5%, glycerol stearate 1%, caprylyl hydroximic acid 0.05%, 1, 3-propylene glycol 0.5%, 1, 2-hexanediol 0.5%, and water in balance, calculated by weight ratio of 100%
S2 weighing curcumin, hydrolyzed corn starch octenyl succinate, polyglycerol 10-laurate, glycerol stearate and water, mixing, and mechanically stirring at 3000r/min for 20min to obtain curcumin mixed solution;
s3, emulsifying and homogenizing: emulsifying the curcumin mixed solution obtained in the step S2 by adopting high-pressure homogenizing shearing for 1.0h, wherein the homogenizing pressure is 16000psi, and repeating for 2 times;
s4, respectively adding the rest caprylyl hydroximic acid, 1, 3-propylene glycol and 1, 2-hexanediol into the curcumin mixed solution obtained by homogenizing in the step S3, and uniformly stirring to obtain curcumin emulsion;
s5, uniformly mixing the ectoin and the madecassoside with the curcumin emulsion prepared in the step S4 according to a proportion to obtain the composition.
Example 3
A composition of curcumin, ectoin and madecassoside with synergistic anti-inflammatory action is prepared from ectoin and madecassoside 1:99:19, and curcumin in the emulsion (8%). The preparation method comprises the following preparation process steps:
s1, curcumin emulsification and dispersion: the curcumin emulsion comprises 10% of curcumin, 8% of hydrolyzed corn starch octenyl succinate, 2% of polyglycerol 10-laurate, 3% of glycerol stearate, 0.05% of caprylyl hydroximic acid, 0.5% of 1, 3-propylene glycol, 0.5% of 1, 2-hexanediol and the balance of water, wherein the curcumin emulsion is calculated by 100% by weight;
s2; weighing curcumin, hydrolyzed corn starch octenyl succinate, polyglycerol 10-laurate, glycerol stearate and water, mixing, and mechanically stirring at 3000r/min for 20min to obtain curcumin mixed solution;
s3, emulsifying and homogenizing: emulsifying the curcumin mixed solution obtained in the step S2 by high-pressure homogenizing shearing for 1.5h, wherein the homogenizing pressure is 16000psi, and repeating for 2 times;
s4, respectively adding the rest caprylyl hydroximic acid, 1, 3-propylene glycol and 1, 2-hexanediol into the curcumin mixed solution obtained by homogenizing in the step S3, and uniformly stirring to obtain curcumin emulsion;
s5, uniformly mixing the ectoin and the madecassoside with the curcumin emulsion prepared in the step S4 according to a proportion to obtain the composition.
Example 4
A composition of curcumin, ectoin and madecassoside with synergistic anti-inflammatory action is curcumin emulsion containing ectoin and madecassoside in the ratio of 1:1:1, and the curcumin content in the curcumin emulsion is 12%. The preparation method comprises the following preparation process steps:
s1, curcumin emulsification and dispersion: the 100% curcumin emulsion comprises 12% curcumin, 12% hydrolyzed corn starch octenyl succinate, 1% polyglycerol 10-laurate, 1% glycerol stearate, 0.05% caprylyl hydroximic acid, 0.5% 1, 3-propylene glycol and 0.5% 1, 2-hexanediol, and the balance water;
s2, weighing curcumin, hydrolyzed corn starch octenyl succinate, polyglycerol 10-laurate, glycerol stearate and water, and mixing, mechanically stirring at 3000r/min for 20min to obtain curcumin mixed solution;
s3, emulsifying and homogenizing: emulsifying the curcumin mixed solution obtained in the step S2 by high-pressure homogenizing shearing for 1.5h, wherein the homogenizing pressure is 16000psi, and repeating for 2 times;
s4, respectively adding the rest caprylyl hydroximic acid, 1, 3-propylene glycol and 1, 2-hexanediol into the curcumin mixed solution obtained by homogenizing in the step S3, and uniformly stirring to obtain curcumin emulsion;
s5, uniformly mixing the ectoin and the madecassoside with the curcumin emulsion prepared in the step S4 according to a proportion to obtain the composition.
Example 5
A composition of curcumin, ectoin and madecassoside with synergistic anti-inflammatory action is curcumin emulsion containing ectoin and madecassoside in the ratio of 1 to 199 to 99, and the curcumin content in the curcumin emulsion is 10%. The preparation method comprises the following preparation process steps:
s1, curcumin emulsification and dispersion: the curcumin emulsion comprises 10% of curcumin, 6% of hydrolyzed corn starch octenyl succinate, 4% of polyglycerol 10-laurate, 0.5% of glycerol stearate, 0.05% of caprylyl hydroximic acid, 0.5% of 1, 3-propylene glycol, 0.5% of 1, 2-hexanediol and the balance of water, wherein the curcumin emulsion is calculated by 100% by weight;
s2, weighing curcumin, hydrolyzed corn starch octenyl succinate, polyglycerol 10-laurate, glycerol stearate and water, and mixing, mechanically stirring at 3000r/min for 20min to obtain curcumin mixed solution;
s3, emulsifying and homogenizing: emulsifying the curcumin mixed solution obtained in the step S2 by adopting high-pressure homogenizing shearing for 2.0h, wherein the homogenizing pressure is 16000psi, and repeating for 2 times;
s4, respectively adding the rest caprylyl hydroximic acid, 1, 3-propylene glycol and 1, 2-hexanediol into the curcumin mixed solution obtained by homogenizing in the step S3, and uniformly stirring to obtain curcumin emulsion;
s5, uniformly mixing the ectoin and the madecassoside with the curcumin emulsion prepared in the step S4 according to a proportion to obtain the composition.
Experimental testing
Experimental test of composition of curcumin, ectoin and madecassoside with synergistic anti-inflammatory effect
1. Experimental materials and instruments
RAW264.7 cell line, supplied by any of the Stani Elon Biotech Co., Ltd; DMEM medium (10% FBS, 100IU/mL Penicilin G + 100. mu.g/mL Streptomyces), fetal bovine serum, 24 and 96 well plates, lipopolysaccharide LPS, etc.
3110 type CO2A cell culture box, a CKX-53 type inverted microscope, an SW-CJ-2FD ultra-clean bench, an ME204E electronic balance (0.0001g), a Multiskan GO enzyme-labeling instrument, and the like.
2. Experimental methods
2.1 Experimental groups
A blank group, a model group, samples of examples 1,2, 3, 4 and 5, a control ectoine group (comparative example 1), a control curcumin emulsion (curcumin content is 10%) (comparative example 2) and madecassoside (comparative example 3) are set, and 10 groups are totally included.
2.2 methods
(1) Cell culture: RAW264.7 cells were cultured in DMEM complete medium, 5% CO2, at 37 ℃ in an incubator and conventionally, RAW264.7 cells were cultured to a cell density of 80%.
(2) Cell plating: the cells were digested and resuspended according to the above procedure, the density of the cell suspension being about 105one/mL. The 24-well plate was loaded with 500. mu.L of cell suspension per well, i.e.cells plated at a density of 5 x 104Per well.
(3) Administration: the medium in each well of the 24-well plate was aspirated, and 1 well was left as a model group except for the negative control group, and the other wells were grouped by the amount of drug and the administration concentration, each 500. mu.L of complete medium containing drug was added. The 24-well plate was placed in an incubator and incubation was continued for 24 hours.
(4) LPS (lipopolysaccharide) induced molding: the cells were incubated for about 24 hours, 5. mu.g/mL of LPS solution was added, the medium was aspirated from each well of the 24-well plate, 1 well was left as a negative control, and 500. mu.L of the prepared LPS solution was added to each of the other wells. The 24-well plate was placed in an incubator and incubation was continued for 24 hours.
(5) And (3) standard curve preparation: and (3) sucking 50 mu L of cell supernatant into a 96 plate, adding a Grignard reagent to detect the content of NO, diluting the standard substance to the concentration of 0, 10, 20, 40, 80 and 100 mu M, and placing the diluted standard substance in a microplate reader for measuring the light absorption value (OD) of the concentration of the series of standard substances at the wavelength of 540 nm.
(6) And (3) sample determination: and (3) sucking 50 mu L of cell supernatant into a 96 plate, adding a Grignard reagent to detect the NO content, and placing the cell supernatant into a microplate reader to measure the light absorption value (OD) of a sample at the wavelength of 540 nm.
(7) Data processing: and processing the light absorption value measured by the experiment by using EXCEL software, making a standard curve, and calculating the NO content of the sample group.
(8) Calculating the NO inhibition rate: inhibition rate (model group NO content-sample group NO content)/(model group NO content-blank group NO content) × 100%.
(9) Calculation of synergy index (Berenbaum index): reference (von Neckweed statistical methods of studying drug synergy [ J)]Chinese hygiene statistics, 2005,022(001):44-46.) calculation formula:
wherein Xi: dosage of the i-th drug in combination, Xie: the dose of the ith drug which alone produces the same effect as the combination, n: the number of the drugs used in combination is that when the Berenbaum index is less than 1, the drugs are combined to have a synergistic effect, and when the Berenbaum index is greater than 1, an antagonistic effect is suggested.
3. Results of the experiment
The experimental results of curcumin, ectoin, madecassoside composition, control ectoin (comparative example 1), control curcumin emulsion (comparative example 2), madecassoside (comparative example 3) on the NO inhibition rate and the synergistic index are shown in Table 1, and the results show that: the ectoine compositions of examples 1-5 inhibit NO generation, which is significantly better than that of single ectoine and curcumin emulsion, and Berenbaum index of ectoine, curcumin emulsion and madecassoside is less than 1, indicating that the ectoine composition prepared by the technology of the present invention has synergistic anti-inflammatory effect.
TABLE 1 Experimental results of the inhibition rate and synergistic index of ectoin composition on NO
| Examples | Inhibition ratio (%) | Synergistic index |
| 1 | 66.33 | 0.74682 |
| 2 | 39.59 | 0.5008 |
| 3 | 46.65 | 0.3806 |
| 4 | 34.01 | 0.9111 |
| 5 | 44.80 | 0.3835 |
| Comparative example 1 | 10.19 | |
| Comparative example 2 | 28.11 | |
| Comparative example 3 | 25.47 |
It should be understood that the above-described embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. Any modification, equivalent replacement, and improvement made within the spirit and principle of the present invention should be included in the protection scope of the claims of the present invention.
Claims (5)
1. A composition of curcumin, ectoin and madecassoside with synergistic anti-inflammatory action and application thereof are characterized in that: the composition comprises the following components in percentage by weight: ectoin: the madecassoside is 200-1:200-1:100-1, and the composition is preferably in a ratio of 10-1:200-1: 10-1.
2. A synergistic anti-inflammatory curcumin, ectoin and madecassoside composition as claimed in claim 1, wherein the curcumin emulsion comprises, by weight, 5% to 12.5% curcumin, 5% to 15% hydrolyzed corn starch octenyl succinate, 0.5% to 5% polyglycerol 10-laurate, 0.5% to 5% glycerol stearate, 0.05% caprylyl hydroxamic acid, 0.5% 1, 3-propanediol, 0.5% 1, 2-hexanediol, and balance water.
3. The composition of curcumin, ectoin and madecassoside with synergistic anti-inflammatory action according to claims 1 and 2, the curcumin emulsion is prepared by the following steps: mixing curcumin, hydrolyzed corn starch octenyl succinate, polyglycerol 10-laurate, glycerol stearate and water according to claim 2, mechanically stirring at 3000r/min for 20min to obtain curcumin mixture, emulsifying by high-pressure homogenizing shear for 0.5-2.0 h under the homogenizing pressure of 10000-16000psi, repeating for 2 times, adding caprylyl hydroximic acid, 1, 3-propylene glycol and 1, 2-hexanediol according to claim 2, and stirring.
4. A synergistic anti-inflammatory composition of curcumin, ectoin and madecassoside as claimed in claim 1, which is prepared by mixing the curcumin emulsion as claimed in claim 3 with ectoin and madecassoside as claimed in claim 1.
5. A synergistic anti-inflammatory combination of curcumin, ectoin and madecassoside as claimed in claim 1, for ameliorating skin problems associated with inflammation, such as redness, itching and irritation, skin barrier repair, etc.
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| CN114225007A (en) * | 2021-11-09 | 2022-03-25 | 西安润玉医疗科技有限公司 | Whey protein spray for repairing superficial wound and preparation method thereof |
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Application publication date: 20201002 |