Stable compositions of dihydroartemisinin

Abstract

The present invention provides a stable composition comprising, based on the total weight of the composition: 0.01-1 wt% of dihydroartemisinin; 5 to 36 wt% of a fatty acyl isethionate salt; and an aqueous carrier acceptable in the personal care field. The invention also relates to a personal care product comprising said composition.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of natural pharmaceutical chemistry and the field of cosmetics, in particular to a stable composition formed by coating dihydroartemisinin with fatty acyloxyethyl sulfonate. BACKGROUND

[0002] In today's fast-paced era, people are always hoping that anything can be quickly, accurately and effectively solved under the background of work and life pressure, and they do not want to invest a lot of time and effort in personal daily care and still harvest the desired effect, or other negative effects. In this spirit of pursuit, consumers' demand for functional personal care products is becoming more and more vigorous. Gradually, this demand has extended from stay-on products such as color cosmetics and skin care products to rinse-off products such as personal cleansing and care products. Therefore, cosmetics that take into account both efficacy and safety are increasingly favored by consumers. Among the many functional raw materials, natural sources of functional raw materials have more advantages than a variety of traditional non-natural sources of functional active substances.

[0003] Dihydroartemisinin (DHA) is an extremely important derivative of artemisinin, which has higher bioavailability and easier metabolism than artemisinin, greatly improving its medicinal value. According to research in the medical field, DHA has good effects in terms of anti-malaria, anti-tumor, anti-virus, anti-inflammatory, anti-other parasites, anti-fibrosis, blood pressure reduction, and immune regulation. Existing research has found that dihydroartemisinin not only has the above medical effects, but also has a good inhibitory effect on Malassezia, and can be used as a safe and efficient anti-dandruff ingredient to replace traditional anti-dandruff agents.

[0004] Chinese patent CN109939105A discloses the use of artemisinin and its derivatives in the preparation of drugs and cosmetics for improving the barrier function of the stratum corneum and preventing and treating skin inflammation.

[0005] Chinese patent CN116019734A discloses the anti-dandruff application of dihydroartemisinin. The patent research found that dihydroartemisinin has a significant inhibition zone at a concentration of 5mM and 10mM, and the inhibition zone of 10mM is greater than the positive control OCT, indicating that dihydroartemisinin has a good inhibitory effect on Malassezia.

[0006] However, DHA is difficult to dissolve in water and other aqueous media, and contains a special peroxide group in the molecule, which is unstable to heat, and is easily decomposed by moisture, heat and reducing substances. In order to improve the water solubility and stability of DHA and reduce its toxicity, the current method commonly used in the medical field is to encapsulate DHA into drug-loaded materials. For example, Chiara Righeschi et al. prepared two kinds of DHA-loaded liposomes with egg yolk lecithin and cholesterol, which can significantly reduce the toxicity of DHA to normal cells while improving the water solubility of DHA. Chen Fangwei et al. used hydroxypropyl-β-cyclodextrin (HP-β-CD) as a carrier to encapsulate DHA, and revealed the feasibility of encapsulation by molecular simulation. The results showed that HP-β-CD encapsulated DHA was not only feasible but also could significantly improve the water solubility of DHA. The above cases are all from the field of pharmacy, and there is no new report in the field of daily chemical industry. If DHA can be applied to cosmetic formulations and can stably exert its effect, it has very important significance for expanding its application field.

[0007] The present application unexpectedly found that fatty acyl oxyethyl sulfonate can solubilize DHA, thereby greatly improving the solubility of DHA in aqueous system, and the combination of the two has a stable appearance under high and low temperature and normal temperature conditions. Therefore, the present application provides a stable composition formed by encapsulating dihydroartemisinin with fatty acyl oxyethyl sulfonate. Compared with the prior art, the present application found the problem of product appearance stability of dihydroartemisinin in daily chemical product application, and carried out research with the purpose of obtaining a composition with stable appearance. SUMMARY

[0008] In one aspect, the present application provides a stable composition, which comprises, based on the total weight of the composition:

[0009] 0.01-1% by weight of dihydroartemisinin;

[0010] 5-36% by weight of fatty acyl oxyethyl sulfonate; and

[0011] an aqueous carrier acceptable in the field of personal care.

[0012] In a preferred embodiment, the composition of the present application comprises 0.1-0.5% by weight of dihydroartemisinin.

[0013] In a preferred embodiment, the composition of the present application comprises 7-30% by weight of fatty acyl oxyethyl sulfonate, preferably 7-15% by weight of fatty acyl oxyethyl sulfonate.

[0014] In a preferred embodiment, the fatty acyl oxyethyl sulfonate is C 12-18 The fatty acyl oxyethyl sulfonate, more preferably, the fatty acyl oxyethyl sulfonate is cocoyl oxyethyl sulfonate.

[0015] In preferred embodiments, the composition of the present application has a water content greater than 50% by weight.

[0016] In another aspect, the present application also relates to a personal care product comprising the composition of the present application. In preferred embodiments, the personal care product is a shampoo, a facial cleanser, or a body wash. BRIEF DESCRIPTION OF DRAWINGS

[0017] Figure 1 Stability photos of 4-week samples of Examples 1-5 are shown.

[0018] Figure 2 Stability comparison photos of 4-week samples of Example 6 and Comparative Example 1 are shown. DETAILED DESCRIPTION

[0019] The present application provides a composition with stable appearance. The composition is formed by the combination of fatty acyl oxyethyl sulfonate and dihydroartemisinin (DHA), which has stable white appearance and can be used in efficacy type daily chemical products.

[0020] The present study found that fatty acyl oxyethyl sulfonate can wrap DHA, thereby greatly improving its solubility in aqueous system. The combination of the two has stable appearance under high and low temperature and normal temperature conditions, indicating that the stability of DHA is improved after being wrapped by the micelles of fatty acyl oxyethyl sulfonate. The composition has good inhibitory effect on malassezia and can be used in anti-dandruff products instead of traditional anti-dandruff agents.

[0021] The present application utilizes the wrapping, solubilizing and sustained-release effects of the micelles formed by fatty acyl oxyethyl sulfonate, which not only increases the water solubility of DHA, but also improves its stability and reduces its cytotoxicity. Therefore, the composition of the present application greatly expands the application scenarios of DHA.

[0022] For the sake of providing a more concise description, some numerical expressions given herein are not modified by the term "about". It should be understood that whether or not the term "about" is explicitly used, each quantity given herein is intended to refer to the actual given value, and is also intended to refer to an approximate value of the given value that can be reasonably inferred by one of ordinary skill in the art, including an approximate value of the given value caused by experimental and / or measurement conditions.

[0023] For the sake of providing a more concise description, some numerical expressions given herein are recited as a range from about X amount to about Y amount. It should be understood that when a range is recited, the range is not limited to the recited upper and lower limits, but should include the entire range or any amount therebetween.

[0024] Dihydroartemisinin

[0025] Dihydroartemisinin (DHA) is an extremely important derivative of artemisinin, which has higher bioavailability and easier metabolism compared with artemisinin. According to the research in the medical field, DHA has good effects in anti-malaria, anti-tumor, anti-virus, anti-inflammatory, anti-other parasites, anti-fibrosis, antihypertensive and immune regulation, etc. The existing research finds that dihydroartemisinin not only has the above medical effects, but also has a good inhibitory effect on malassezia, which can be used as a safe and efficient anti-dandruff ingredient of natural origin to replace traditional anti-dandruff agents.

[0026] In some embodiments, the composition of the present application comprises 0.01-1% by weight of dihydroartemisinin. In preferred embodiments, the composition of the present application comprises 0.01-0.6% by weight of dihydroartemisinin. In more preferred embodiments, the composition of the present application comprises 0.1-0.5% by weight of dihydroartemisinin.

[0027] Fatty acyl isethionates

[0028] Fatty acyl isethionate is a kind of mild anionic surfactant, which has the advantages of easy foaming, rich foam, extremely low skin irritation and low price, which exactly meets the urgent needs of the market, and has a wide application prospect in soap, facial cleanser, shower gel and shampoo. When the concentration of fatty acyl isethionate in water is higher than its CMC value, stable micellar particles will be formed in the aqueous solution, which can encapsulate hydrophobic ingredients and play a solubilizing effect. At the same time, in the process of cleaning and dilution, the concentration of surfactant becomes lower and lower, and the micellar form changes. When the concentration is lower than the CMC value, the micelles open, and the encapsulated ingredients can be slowly released, so it also has a slow-release effect on active ingredients.

[0029] The present application finds that fatty acyl isethionate can encapsulate DHA, thereby greatly improving the solubility of DHA in aqueous system. The combination of the two has a stable appearance under high and low temperature and normal temperature conditions, indicating that the stability of DHA is improved after being encapsulated by the micelles of fatty acyl isethionate. The composition has a good inhibitory effect on malassezia, and can be used in anti-dandruff products to replace traditional anti-dandruff agents.

[0030] In some embodiments, the fatty acyl isethionate used in the composition of the present application is C 12-18 fatty acyl isethionate. In preferred embodiments, the fatty acyl isethionate used in the composition of the present application is C 12-16 fatty acyl isethionate, more preferably C 14Fatty acyl isethionate. In preferred embodiments, the fatty acyl isethionate employed in the compositions of the present application is sodium cocoyl isethionate. In particular embodiments, the present application employs sodium cocoyl isethionate available under the trade name PURE ACT I-78C-A from INCOSE (Beijing) Co. Ltd.

[0031] In some embodiments, the compositions of the present application comprise 5-36 wt.% fatty acyl isethionate. In preferred embodiments, the compositions of the present application comprise 7-30 wt.% fatty acyl isethionate. In a particular embodiment, the compositions of the present application comprise 15 wt.% fatty acyl isethionate.

[0032] Stable compositions

[0033] The present application provides a multifunctional white composition which greatly improves the solubility and stability of DHA in aqueous system, and can be applied in efficacy daily chemical products. The present technology can greatly expand the application of natural active ingredient-dihydroartemisinin in other fields.

[0034] In addition to the above components, the compositions of the present application also contain a balance of water. Thus, the compositions of the present application can also include water or other aqueous carriers.

[0035] In preferred embodiments, the compositions of the present application have a water content of at least 50 wt.%. For example, the compositions of the present application have a water content of greater than 50 wt.%, greater than 55 wt.%, greater than 60 wt.%, greater than 65 wt.%, greater than 70 wt.%, greater than 75 wt.%, or greater than 80 wt.%. In some embodiments, the compositions of the present application have a water content of 50-95 wt.%, preferably 60-90 wt.%, 60-88 wt.%, 65-88 wt.%, 70-88 wt.%, or 75-88 wt.%.

[0036] Personal care products

[0037] The present application also relates to personal care products which can comprise the compositions of the present application. In particular embodiments, such personal care products can be in the form of a facial cleanser, a body wash, a shampoo, or the like. In preferred embodiments, the personal care product is a hair wash product.

[0038] The product can be applied to the skin or hair of a user in any desired manner. In some aspects, the product can be applied directly by hand, or a device such as a towel, sponge, or other apparatus can be used to apply the product. The composition is advantageously applied to wetted hair or skin in order to facilitate application. The composition can be left on the area of application for a desired level of time, such as from about 5 seconds to about 5 minutes, and then rinsed off with water to remove from the area of application.

[0039] Examples

[0040] The application will be further described in conjunction with specific examples. It is necessary to point out here that the examples are only used to further illustrate the application and cannot be understood as limiting the scope of protection of the application. Those skilled in the art can make some non-essential improvements and adjustments according to the content of the above application. The test methods in the following examples are not specified, which are usually carried out according to the conventional conditions or the conditions recommended by the manufacturers. Unless otherwise specified, all percentages and parts are by weight.

[0041] The experimental materials used in the examples of the application are as follows:

[0042] Dihydroartemisinin, purity > 90%, provided by Institute of Chinese Medicine, Chinese Academy of Chinese Medical Sciences;

[0043] Sodium cocoyl isethionate, trade name PUREACT I-78C-A, active content 100%, purchased from Innospec Chemical (Beijing) Co., Ltd.;

[0044] Disodium lauryl ether sulfosuccinate, trade name Ucefactant MES L30, active content 30%, purchased from Guangzhou Xingye Science and Technology Co., Ltd.

[0045] Example 1: Preparation of a stable composition of dihydroartemisinin wrapped by fatty acyloxyethyl sulfonate

[0046] Take 15 parts by mass of sodium cocoyl isethionate and add it to a beaker containing 50 parts by mass of deionized water. Mix and stir at a speed of 200 rpm under a water bath at 70°C until completely dissolved. Cool to 25°C, take 0.01 parts by mass of dihydroartemisinin and place it in the beaker. Mix and stir at 200 rpm until the dihydroartemisinin is completely dissolved. Then make up to 100 parts with deionized water and continue to stir at a speed of 200 rpm for 10 minutes until completely dispersed and uniform.

[0047] Example 2: Preparation of a stable composition of dihydroartemisinin wrapped by fatty acyloxyethyl sulfonate

[0048] Take 15 parts by mass of sodium cocoyl isethionate and add it to a beaker containing 50 parts by mass of deionized water. Mix and stir at a speed of 200 rpm under a water bath at 70°C until completely dissolved. Cool to 25°C, take 0.05 parts by mass of dihydroartemisinin and place it in the beaker. Mix and stir at 200 rpm until the dihydroartemisinin is completely dissolved. Then make up to 100 parts with deionized water and continue to stir at a speed of 200 rpm for 10 minutes until completely dispersed and uniform.

[0049] Example 3: Preparation of stable composition of dihydroartemisinin coated with fatty acyloxy ethyl sulfonate salt

[0050] Take 15 parts by mass of sodium cocoyl isethionate, add to a beaker containing 50 parts by mass of deionized water, mix and stir at a speed of 200 rpm under 70°C water bath heating until completely dissolved; cool to 25°C, take 0.15 parts by mass of dihydroartemisinin, place in the beaker, mix and stir at 200 rpm until the dihydroartemisinin is completely dissolved, then make up to 100 parts with deionized water, continue to stir at a speed of 200 rpm for 10 minutes until completely dispersed and uniform.

[0051] Example 4: Preparation of stable composition of dihydroartemisinin coated with fatty acyloxy ethyl sulfonate salt

[0052] Take 15 parts by mass of sodium cocoyl isethionate, add to a beaker containing 50 parts by mass of deionized water, mix and stir at a speed of 200 rpm under 70°C water bath heating until completely dissolved; cool to 25°C, take 0.85 parts by mass of dihydroartemisinin, place in the beaker, mix and stir at 200 rpm until the dihydroartemisinin is completely dissolved, then make up to 100 parts with deionized water, continue to stir at a speed of 200 rpm for 10 minutes until completely dispersed and uniform.

[0053] Example 5: Preparation of stable composition of dihydroartemisinin coated with fatty acyloxy ethyl sulfonate salt

[0054] Take 15 parts by mass of sodium cocoyl isethionate, add to a beaker containing 50 parts by mass of deionized water, mix and stir at a speed of 200 rpm under 70°C water bath heating until completely dissolved; cool to 25°C, take 1 part by mass of dihydroartemisinin, place in the beaker, mix and stir at 200 rpm until the dihydroartemisinin is completely dissolved, then make up to 100 parts with deionized water, continue to stir at a speed of 200 rpm for 10 minutes until completely dispersed and uniform.

[0055] Example 6: Preparation of stable composition of dihydroartemisinin coated with fatty acyloxy ethyl sulfonate salt

[0056] Take 15 parts by mass of sodium cocoyl isethionate, add to a beaker containing 50 parts by mass of deionized water, mix and stir at a speed of 200 rpm under 70°C water bath heating until completely dissolved; cool to 25°C, take 0.5 parts by mass of dihydroartemisinin, place in the beaker, mix and stir at 200 rpm until the dihydroartemisinin is completely dissolved, then make up to 100 parts with deionized water, continue to stir at a speed of 200 rpm for 10 minutes until completely dispersed and uniform.

[0057] Test Example 1: Stability test

[0058] The appearance of Examples 1-6 was tested, and stability was investigated.

[0059] The stability evaluation method was as follows: the compositions prepared in Examples 1-5 were placed in constant-temperature ovens at high temperature (40°C), low temperature (4°C), and room temperature (25°C), and were investigated for 30 days. Whether or not solid particles were precipitated, whether or not the sample was jellied, whether or not the sample was layered, whether or not the sample was discolored, and the like were observed every week. If the sample was normal without any change before and after a certain time within 30 days, then it was indicated as "pass"; if solid particles were precipitated, then it was indicated as "precipitation"; if a viscous gel that was not easy to flow was produced, then it was indicated as "jellied"; if the sample was layered, then it was indicated as "layered"; and if the sample was discolored, then it was indicated as "discolored". The results are shown in the following table.

[0060] Table 1: Stability investigation of different prepared compositions

[0061]

[0062]

[0063] As can be seen from Table 1, when the amount of dihydroartemisinin added was between 0.01 and 1 parts, dihydroartemisinin was completely dispersed in an aqueous solution containing 15 parts of sodium cocoyl isethionate to form a white liquid, and the formed composition maintained a stable white appearance at high temperature (40°C), low temperature (4°C), and room temperature (25°C) for 1-4 weeks.

[0064] Comparative Example 1: Preparation of a lauryl alcohol polyether sulfosuccinate disodium and dihydroartemisinin composition

[0065] 50 parts by mass of lauryl alcohol polyether sulfosuccinate disodium was placed in a beaker, and 0.5 parts by mass of dihydroartemisinin was slowly added under stirring at a stirring speed of 200 rpm. After the dihydroartemisinin was completely dissolved by stirring, deionized water was added to make up to 100 parts, and stirring was continued at a stirring speed of 200 rpm for 10 minutes until complete dispersion.

[0066] Test Example 2: Stability test

[0067] The appearance of Comparative Example 1 was tested, and stability was investigated.

[0068] The stability evaluation method is as follows: the composition prepared in Comparative Example 1 is placed in a constant temperature oven at high temperature (40°C), low temperature (4°C), and room temperature (25°C), and observed for 30 days to observe whether solid particles are precipitated, whether the sample is jellified, whether it is layered, whether it is discolored, and the like. If the sample is normal with no change before and after a certain time within 30 days, it is indicated as "pass"; if solid particles are precipitated, it is indicated as "precipitation"; if a viscous gel that is not easy to flow is generated, it is indicated as "jellification"; if the sample is layered, it is indicated as "layering"; and if the sample is discolored, it is indicated as "discoloration". The results are shown in the following table.

[0069] Table 2: Stability observation of the composition prepared in Comparative Example 1

[0070]

[0071] As can be seen from the results of Comparative Example 1, the composition of 50% lauryl alcohol polyether sulfosuccinate disodium and 0.5% dihydroartemisinin appears to be yellow at room temperature (25°C) and high temperature (40°C), and the higher the temperature, the more obvious the discoloration. Although Comparative Example 1 and Example 6 are both anionic surfactants, and the effective content of the anionic surfactants is 15%, and the dihydroartemisinin is 0.5%, the lauryl alcohol polyether sulfosuccinate disodium and dihydroartemisinin of Comparative Example 1 cannot form a composition with stable appearance, while the sodium cocoyl isethionate in the examples can.

Claims

1. A stable composition, comprising, by weight of the total composition: 0.01-1% by weight of dihydroartemisinin; 5-36% by weight fatty acyl hydroxyethyl sulfonate; and Aqueous carriers acceptable for the personal care field.

2. The composition according to claim 1, characterized in that, The composition contains 0.1-0.5% by weight of dihydroartemisinin.

3. The composition according to claim 1, characterized in that, The composition contains 7-30% by weight of fatty acyl hydroxyethyl sulfonate.

4. The composition according to claim 1, characterized in that, The composition contains 7-15% by weight of fatty acyl hydroxyethyl sulfonate.

5. The composition according to claim 1, characterized in that, The fatty acylhydroxyethyl sulfonate is C 12-18 Fatty acyl hydroxyethyl sulfonate.

6. The composition according to claim 1, characterized in that, The fatty acyl hydroxyethyl sulfonate is a cocoyl hydroxyethyl sulfonate salt.

7. The composition according to claim 1, characterized in that, The composition has a water content greater than 50% by weight.

8. A personal care product comprising the composition as described in any one of claims 1-7.

9. The personal care product of claim 8, wherein the personal care product is a shampoo, facial cleanser, or shower gel.

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