CN117442522A - A high-content, high-stability ginsengdiol preparation and its preparation method and application - Google Patents

Abstract

The invention relates to a high-content and high-stability panaxadiol preparation, a preparation method and application thereof. The preparation solves the problems of poor solubility, low bioavailability, limited application, etc. of the ginseng diol. The panaxadiol preparation has the skin soothing effect in an in-vitro 3D skin soothing model, and can be widely applied to product dosage forms such as functional cosmetic emulsion, aqua, spray and the like.

Description

A high-content, high-stability ginsengdiol preparation and its preparation method and application

Technical field

The invention belongs to the technical field of pharmaceutical preparations and relates to a high-content and high-stability ginsengdiol preparation and its preparation method and application.

Background technique

Ginsenosides are the main active ingredients of ginseng, Panax notoginseng, etc., and have attracted widespread attention because of their anti-inflammatory, soothing, antioxidant, vasodilation, anti-allergic, and anti-tumor effects. However, ginsenosides contain many sugar groups, which are difficult to be directly absorbed and utilized by the human body after taking them. They need to be metabolized in the human body to hydrolyze the sugar groups of these saponins step by step to produce secondary saponins (original saponins) with smaller molecular weights that are easier for the body to absorb. Pananaxadiol, protopanaxatriol) or aglycone (panaxadiol, panaxatriol). Panaxadiol (PD) is a sapogen aglycone containing two OH obtained from the strong acid hydrolysis of diol saponin or protopanaxadiol. The purpose of hydrolysis is to improve the pharmaceutical activity of saponins in the body (anti-inflammatory and soothing, anti-tumor, neuroprotective, cardiovascular and cerebrovascular regulation). However, panaxadiol has poor water solubility and low bioavailability, so its application in various fields is relatively limited.

The 3D skin model is to obtain a small amount of living skin tissue from the body, separate the cells from the tissue, and culture and expand them in vitro. The amplified cells and biological materials are then mixed in a certain ratio to adhere the cells. 3D skin model grown from biomaterials. The principle of the 3D skin soothing model is to simulate and reproduce the biological response of real skin during the soothing process by imitating the cells and tissue structures in the skin, so as to reflect the active ingredients to reduce or reverse the inflammatory response in the model to soothe ( Collect skin culture fluid for detection of inflammatory factors IL-1α and IL-8, and determine whether it has soothing effect based on relative expression levels).

Chinese patent application CN103505462 B discloses a "use of 20(S)-protopanaxadiol" used in protopanaxadiol injection to treat myocardial ischemia. Chinese patent application CN1526407A discloses a "protopanaxadiol freeze-dried emulsion and its preparation method" for intravenous targeted drug delivery to the lymphatic system. Chinese patent application CN 103800286A discloses a "20(S)-protopanaxadiol self-microemulsion composition and its preparation method and application." The self-microemulsion is composed of protopanaxadiol, nonionic emulsifiers, saturated fatty acids, etc. Composition, but it uses emulsifiers and co-emulsifiers. Some ingredients are highly cytotoxic and difficult to add to cosmetics or pharmaceutical excipients. The maximum content of protopanaxadiol in this preparation is 20%. Although the bioavailability is improved, it is still difficult to add in product development. There are also certain limitations.

Contents of the invention

In view of the shortcomings of the existing technology, the purpose of the present invention is to provide a high-content, high-stability ginsengdiol preparation and its preparation method and application. The content of ginsengdiol in the ginsengdiol preparation of the invention is as high as 30%, which solves the problems of low water solubility and low bioavailability of ginsengdiol. The emulsifier used meets the technical specification requirements of cosmetics and can meet the application in the field of cosmetics and pharmaceutical excipients.

In order to achieve the purpose of this invention, the present invention adopts the following technical solutions:

In a first aspect, the present invention provides a high-content, high-stability panaxadiol preparation. The raw materials for preparing the panaxadiol preparation include panaxadiol, oil, emulsifier and co-emulsifier.

The present invention mainly uses ginsengdiol as raw material to prepare a high-content and high-stability ginsengdiol water-soluble preparation to improve external skin absorption, increase its bioavailability, and broaden the application of ginsengdiol in cosmetics and pharmaceutical excipients. The ginsengdiol preparation of the present invention has a high ginsengdiol content, and the mass percentage of ginsengdiol in the preparation is more than 30%, and the ginsengdiol preparation can be dissolved in water at any ratio, and is clear, translucent and non-toxic. After precipitating, there is almost no significant change in the content of ginsengdiol after being left for 6 months. The appearance is still clear and translucent, with good solubility and high stability. This preparation solves the problems of poor solubility, low bioavailability and limited use of ginsengdiol. Moreover, the ginsengdiol preparation has skin soothing effect in the in vitro 3D skin soothing model, and can be widely used in functional cosmetic emulsions, lotions, sprays and other product dosage forms.

Preferably, the ginsengdiol preparation includes ginsengdiol 10-40%, oil 10-20%, emulsifier 30-40%, and co-emulsifier 10-30% in terms of mass percentage.

The mass percentage of ginsengdiol can be selected from 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, 30%, 32%, 34% , 36%, 38%, 40%, etc., the mass percentage of the grease can be selected from 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19% , 20%, etc. The mass percentage of the emulsifier can be selected from 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, etc. The mass percentage of the co-emulsifier can be selected from 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, 30%, etc., within the above numerical range Other specific point values can be selected, so I won’t go into details here.

Preferably, the oil or fat includes any one or a combination of at least two of thornberry oil, camellia seed oil, olive oil or grape seed oil, and further preferably thornberry oil.

The present invention creatively discovered that the effect of Amaranthus sinensis oil is better than that of other oils, and it can cooperate with Panaxadiol to enhance its soothing effect.

Preferably, the emulsifier includes PEG-100 stearate and/or polysorbate 60; further preferably, PEG-100 stearate and polysorbate 60 are used.

The present invention found that the addition of PEG-100 stearate and polysorbate 60 can further improve the stability of the preparation, and the emulsifier used is a combination emulsifier of nonionic emulsifiers with an HLB value greater than 12.

Preferably, the mass ratio of the PEG-100 stearate and polysorbate 60 is (2-3):1, where the specific point values in (2-3) can be selected from 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, etc. Other specific point values within the above numerical range can be selected, and I will not go into details here.

The present invention found that the emulsifier added in the above ratio can better exert the emulsifying effect of the two emulsifiers, and is easier to be absorbed through the skin so that ginsengdiol can be evenly dispersed in the preparation system without precipitation, and its aqueous solution can also be clear and translucent, and more Easily absorbed through skin.

Preferably, the co-emulsifier includes any one or a combination of at least two of glycerin, butylene glycol, pentanediol, polyethylene glycol or 1,2-propylene glycol.

In addition to increasing the emulsification effect, co-emulsifiers can also increase the solubility of ginsengdiol. Among them, glycerin has a promoting effect on reducing the particle size of the entire preparation, reducing surface tension, and enabling better formation of microemulsion droplets.

In a second aspect, the present invention provides a method for preparing a high-content, high-stability ginsengdiol preparation according to the first aspect. The preparation method includes: mixing ginsengdiol with oil and fat, and then mixing it with an emulsifier Mix with co-emulsifier to get it.

The preparation method of the ginsengdiol preparation of the present invention creatively uses a base oil to first dissolve the ginsengdiol so that the ginsengdiol is fully wrapped in the oil phase, and then adds an emulsifier and a co-emulsifier. On the one hand, the ginsengdiol is dissolved The alcohol is dispersed and dissolved in the oil phase, making it easier to be emulsified by the emulsifier and improving the emulsification effect. On the other hand, using this preparation method can improve the stability of ginsengdiol.

Preferably, the mixing temperature is independently 50-70°C, such as 50°C, 52°C, 54°C, 56°C, 58°C, 60°C, 62°C, 64°C, 66°C, 68°C, 70°C, etc. , other specific point values within the above numerical range can be selected, so I will not go into details here.

In a third aspect, the present invention provides an application of the panaxadiol preparation according to the first aspect in the preparation of cosmetics with soothing effects.

Preferably, the added amount of ginsengdiol preparation in the cosmetics is 0.05%-1%, such as 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5 %, 0.6%, 0.7%, 0.8%, 0.9%, 1%, etc. Other specific point values within the above numerical range can be selected, so I will not go into details here.

Compared with the existing technology, the present invention has the following beneficial effects:

The ginsengdiol preparation of the present invention has a high ginsengdiol content, and the mass percentage of ginsengdiol in the preparation is more than 30%, and the ginsengdiol preparation can be dissolved in water at any ratio, and is clear, translucent and non-toxic. After precipitating, there is almost no significant change in the content of ginsengdiol after being left for 6 months. The appearance is still clear and translucent, with good solubility and high stability. This preparation solves the problems of poor solubility, low bioavailability and limited use of ginsengdiol. Moreover, the ginsengdiol preparation has skin soothing effect in the in vitro 3D skin soothing model, and can be widely used in functional cosmetic emulsions, lotions, sprays and other product dosage forms.

Description of the drawings

Figure 1 is the liquid chromatogram of ginsengdiol preparation and ginsengdiol standard.

Figure 2 is a graph showing the results of relative expression levels of IL-1α.

Detailed ways

The technical solution of the present invention will be further described below through specific implementations. Those skilled in the art should understand that the embodiments are only to help understand the present invention and should not be regarded as specific limitations of the present invention.

The functional ingredients contained in the products involved in the following examples and comparative examples are sourced as follows (only the functional ingredients are reflected, and the necessary auxiliary ingredients contained in other commercially available raw materials will not be described again):

Greenberry oil, olive oil, grape seed oil, camellia seed oil, PEG-100 stearate, and polysorbate-6 were all purchased from Shanghai Yuanye Biotechnology Co., Ltd.

Example 1

This embodiment provides a ginsengdiol preparation. The ginsengdiol includes 1 part of ginsengdiol with a content of 95%, 0.5 part of ginseng oil, 1 part of emulsifier, and 0.5 part of glycerin in terms of parts by mass. The emulsifier is PEG-100 stearate and polysorbate-60, and their mass ratio is 2.5:1.

Its preparation method is:

Mix ginsengdiol and Amaranthus lucidum oil at 60°C, then mix with emulsifier and glycerin, and homogenize for 10 minutes to obtain.

Example 2

This embodiment provides a ginsengdiol preparation. The ginsengdiol includes 0.9 parts of ginsengdiol with a content of 95%, 0.4 parts of ginseng oil, 1.3 parts of emulsifier, and 0.8 parts of glycerin in terms of parts by mass. The emulsifiers are PEG-100 stearate and polysorbate-60, and their mass ratio is 3:1.

Refer to Example 1 for the preparation method.

Example 3

This embodiment provides a ginsengdiol preparation. The ginsengdiol includes 1.2 parts of ginsengdiol with a content of 95%, 0.6 parts of ginseng oil, 0.9 parts of emulsifier, and 0.3 parts of glycerin in terms of parts by mass. The emulsifiers are PEG-100 stearate and polysorbate-60, and their mass ratio is 2:1.

Refer to Example 1 for the preparation method.

Example 4

This embodiment provides a ginsengdiol preparation, which differs from Example 1 only in that the same amount of Amaranthus sinensis oil is replaced by camellia seed oil, and the other ingredients and content remain unchanged.

Refer to Example 1 for the preparation method.

Example 5

This embodiment provides a ginsengdiol preparation, which differs from Example 1 only in that the same amount of cinnamon oil is replaced by olive oil, and the other ingredients and content remain unchanged.

Refer to Example 1 for the preparation method.

Example 6

This embodiment provides a ginsengdiol preparation, which differs from Example 1 only in that the same amount of ginseng oil is replaced by grape seed oil, and the other ingredients and content remain unchanged.

Refer to Example 1 for the preparation method.

Example 7

This embodiment provides a ginsengdiol preparation, which is different from Example 1 only in that 0.5 part of the ginseng oil is replaced by 0.2 part of the tangerine oil, and the other ingredients and content remain unchanged.

Refer to Example 1 for the preparation method.

Example 8

This embodiment provides a ginsengdiol preparation, which differs from Example 1 only in that 0.5 part of the ginseng oil is replaced by 1 part of the tangerine oil, and the other ingredients and content remain unchanged.

Refer to Example 1 for the preparation method.

Example 9

This embodiment provides a ginsengdiol preparation, which differs from Example 1 only in that 1 part of the emulsifier is replaced by 1.5 parts of the emulsifier, and the other ingredients and content remain unchanged.

Refer to Example 1 for the preparation method.

Example 10

This embodiment provides a ginsengdiol preparation, which differs from Example 1 only in that 1 part of the emulsifier is replaced by 0.6 part of the emulsifier, and the other ingredients and content remain unchanged.

Other ingredients and contents remain unchanged.

Refer to Example 1 for the preparation method.

Example 11

This embodiment provides a ginsengdiol preparation. The ginsengdiol includes 1 part of ginsengdiol with a content of 95%, 0.5 part of ginseng oil, 1 part of emulsifier, and 0.5 part of glycerin in terms of parts by mass. The emulsifiers are PEG-100 stearate and polysorbate-60, and their mass ratio is 1:1.

Refer to Example 1 for the preparation method.

Example 12

This embodiment provides a ginsengdiol preparation. The ginsengdiol includes 1 part of ginsengdiol with a content of 95%, 0.5 part of ginseng oil, 1 part of emulsifier, and 0.5 part of glycerin in terms of parts by mass. The emulsifiers are PEG-100 stearate and polysorbate-60, and their mass ratio is 4:1.

Refer to Example 1 for the preparation method.

Example 13

This embodiment provides a ginsengdiol preparation. The ginsengdiol includes 1 part of ginsengdiol with a content of 95%, 0.5 part of ginseng oil, 1 part of emulsifier, and 0.5 part of glycerin in terms of parts by mass. The emulsifier is PEG-100 stearate.

Refer to Example 1 for the preparation method.

Example 14

This embodiment provides a ginsengdiol preparation. The ginsengdiol includes 1 part of ginsengdiol with a content of 95%, 0.5 part of ginseng oil, 1 part of emulsifier, and 0.5 part of glycerin in terms of parts by mass. The emulsifier is polysorbate-60.

Refer to Example 1 for the preparation method.

Example 15

This embodiment provides a ginsengdiol preparation, which is different from Example 1 only in the preparation method.

Its preparation method is:

Mix ginsengdiol, oil, emulsifier and glycerin together at 60°C and homogenize for 10 minutes to get it.

Comparative example 1

This comparative example provides a ginsengdiol preparation, which differs from Example 1 only in that it does not contain Amaranthus lucidum oil, and its reduced mass is distributed in proportion to the mass of ginsengdiol, emulsifier and glycerin.

Refer to Example 1 for the preparation method.

Test example 1

Stability investigation and determination of ginsengdiol content

Test samples: Examples 1-15, Comparative Example 1

Test method: Place the sample to be tested for 6 months, and detect the content of ginsengdiol at the 3-month and 6-month time points. Mix 100 μL of the sample to be tested with 900 μL of deionized water, and use ELSD-HPLC to determine the ginsengdiol content.

Chromatographic column: ZORBAX SB-C18 column (4.6×250mm; 5-Micron); mobile phase: water (A)-acetonitrile (B) (0-5min; 50%B-60%B; 5-10min; 60%B -70%B; 10-15min; 70%B-75%B; 15-20min; 75%B; 20-35min 75%B-80%B) Evaporation temperature: 75℃; Atomization temperature: 30℃; Gas Flow rate: 1.8SLM; flow rate: 1mL/min; column temperature: 40°C; injection volume: 10μL.

The liquid chromatograms of ginsengdiol preparation and ginsengdiol standard are shown in Figure 1.

Table 1

It can be seen from the data in Table 1 that the ginsengdiol preparation of the present invention has a high ginsengdiol content. The mass percentage of ginsengdiol in this preparation is more than 30%. After being left for 6 months, the ginsengdiol content is almost There is no obvious change, the appearance is still clear and translucent, the solubility is good, and the stability is high.

Test example 2

Efficacy testing of in vitro reconstituted 3D epidermal model

Test samples: Example 1, Example 4 and ginsengdiol monomer

Test Methods:

Set up a blank control group, SLS induction stimulation group, positive control group (dexamethasone, dex) and sample group (concentration of the sample group are all 600 μg/mL), and incubate them in a 37°C, 5% _CO2 incubator for 2 hours, except for the blank group. Except for the control group, SLS was added to each well and incubated in the incubator for 24 hours. The cell supernatant was collected and the inhibitory effect of IL-1α was detected by ELISA. The data were analyzed using one-way variance analysis, and the evaluation results are shown in Table 2. Among them, Example 1 has a significant inhibitory effect on IL-1α (P<0.001, ****), and Example 4 has a slightly weaker inhibitory effect on IL-1α, as shown in Figure 2.

Table 2

sample name 3D skin soothing model efficacy results Example 1 Significantly inhibits the expression of IL-1α Example 4 Inhibit the expression of IL-1α Panaxadiol monomer Inhibit the expression of IL-1α

As can be seen from Table 2 and Figure 2, the ginsengdiol preparation of the present invention has a significantly excellent inhibitory effect on IL-1α. The soothing effect of panaxadiol preparations can be judged based on the relative expression of inflammatory factors IL-1α and IL-8. If it inhibits the expression of one of the factors, it can be determined that the product has a soothing effect. Moreover, the soothing effect of the ginsengdiol preparation of the present invention is better than that of ginsengdiol monomer, and after the oil is replaced by other oils and fats, the effect is equivalent to that of ginsengdiol monomer, indicating that the effect of ginsengdiol monomer is The oil works with Panaxadiol to enhance the soothing effects of Panaxadiol.

The applicant declares that the present invention illustrates a high-content, high-stability panaxadiol preparation of the present invention and its preparation method and application through the above-mentioned examples, but the present invention is not limited to the above-mentioned examples, that is, it does not mean that The present invention must rely on the above-mentioned embodiments to be implemented. Those skilled in the art should understand that any improvements to the present invention, equivalent replacement of raw materials of the product of the present invention, addition of auxiliary ingredients, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details of the above embodiments. Within the scope of the technical concept of the present invention, a variety of simple modifications can be made to the technical solution of the present invention. These simple modifications All belong to the protection scope of the present invention.

In addition, it should be noted that each of the specific technical features described in the above-mentioned specific embodiments can be combined in any suitable manner without conflict. In order to avoid unnecessary repetition, the present invention combines various possible combinations. The combination method will not be further explained.

Claims (10)

1. A high-content and high-stability panaxadiol preparation, which is characterized by comprising panaxadiol, grease, an emulsifier and a coemulsifier.

2. The high content, high stability panaxadiol formulation of claim 1, wherein the panaxadiol formulation comprises 10-40% panaxadiol, 10-20% fat, 30-40% emulsifier and 10-30% co-emulsifier in mass percent.

3. The high content, high stability panaxadiol formulation of claim 1 or 2, wherein the oil comprises any one or a combination of at least two of prinsepia utilis royle oil, camellia seed oil, olive oil or grape seed oil, preferably prinsepia utilis royle oil.

4. A high content, high stability panaxadiol formulation according to any one of claims 1-3, wherein the emulsifier comprises PEG-100 stearate and/or polysorbate 60; PEG-100 stearate and polysorbate 60 are preferred.

5. The high content, high stability panaxadiol formulation of any one of claims 1-4, wherein the mass ratio of PEG-100 stearate to polysorbate 60 is (2-3): 1.

6. The high content, high stability panaxadiol formulation of any one of claims 1-5, wherein the co-emulsifier comprises any one or a combination of at least two of glycerol, butylene glycol, pentylene glycol, polyethylene glycol, or 1, 2-propylene glycol.

7. The method for preparing a high content, high stability panaxadiol formulation according to any one of claims 1-6, wherein the method comprises: mixing panaxadiol with oil, and mixing with emulsifier and auxiliary emulsifier.

8. The method for preparing a high content, high stability panaxadiol formulation of claim 7, wherein the temperature of mixing is independently 50-70 ℃.

9. Use of the panaxadiol formulation according to any one of claims 1-6 for the preparation of cosmetics with soothing efficacy.

10. The use according to claim 9, wherein the amount of the panaxadiol preparation added in the cosmetic is 0.05-1%.