Effervescent lyophilized tablets containing lyoprotectants, and methods of making and using the same

Abstract

The present application relates to a kind of containing lyophilization protectant efficacy lyophilized tablet and its preparation method and application, the efficacy lyophilized tablet includes ascorbic acid or its derivative, humectant, whitening agent, pH adjusting agent and lyophilization protectant;The lyophilization protectant includes the combination of polyethylene glycol, bis-PEG-18 methyl ether dimethyl silane, mannitol.The present application creatively adds lyophilization protectant in the lyophilized tablet of ascorbic acid or its derivative, can adjust the skin feel and solubility of lyophilized tablet whole while improving the appearance of lyophilized tablet using lyophilization mould, also can keep the stability of active substance in lyophilized tablet.Lyophilization protectant uses the combination of polyethylene glycol, bis-PEG-18 methyl ether dimethyl silane, mannitol, three mutually cooperate, synergistic effect, so that lyophilized tablet has excellent smooth feeling while improving toughness and hardness, improves the experience of using.

Description

Technical Field

[0001] This invention belongs to the field of cosmetic technology and relates to a functional freeze-dried tablet containing a freeze-drying protectant, its preparation method, and its application. Background Technology

[0002] In the skincare industry, freeze-dried tablets have garnered significant attention due to their superior stability against heat-sensitive active ingredients such as vitamin C and peptides. Currently, the mainstream production process involves filling liquid serum into plastic molds, freeze-drying them, and then demolding them. However, this technology still has significant drawbacks in practical applications:

[0003] First, freeze-dried tablets are difficult to demold, easily resulting in problems such as adhesion, breakage, or rough surface, leading to poor product appearance and low yield. Second, to adapt to the freeze-drying process, the formulation design often focuses on physical molding, while the means for fine adjustment of dissolution speed and skin texture (such as moisturizing, smoothness, and absorption) are limited, making it difficult to meet consumers' diverse needs for a high-end skincare experience. Third, from a production perspective, the existing process relies on manual demolding, which is inefficient, and common mold materials may exacerbate adhesion, affecting the efficiency of large-scale production.

[0004] Therefore, how to achieve high-quality appearance, excellent skin feel, and good solubility of lyophilized tablets while ensuring high stability of active ingredients has become a key technical problem that urgently needs to be solved in this field. Summary of the Invention

[0005] To address the shortcomings of existing technologies, the present invention aims to provide a functional freeze-dried tablet containing a freeze-drying protectant, its preparation method, and its application.

[0006] To achieve this objective, the present invention employs the following technical solution:

[0007] In a first aspect, the present invention provides a functional lyophilized tablet containing a lyophilization protectant, the functional lyophilized tablet comprising ascorbic acid or its derivatives, a moisturizer, a whitening agent, a pH adjuster and a lyophilization protectant; the lyophilization protectant comprising a combination of polyethylene glycol, bis-PEG-18 methyl ether dimethylsilane and mannitol.

[0008] This invention creatively incorporates a freeze-drying protectant into freeze-dried tablets containing ascorbic acid or its derivatives. This improves the appearance of the freeze-dried tablets produced using freeze-drying molds, while also adjusting the overall skin feel and solubility, and maintaining the stability of the active ingredients. The freeze-drying protectant uses a combination of polyethylene glycol, bis-PEG-18 methyl ether dimethylsilane, and mannitol. These three components work synergistically to enhance the freeze-dried tablets' toughness and hardness while providing excellent smoothness, thus improving the user experience.

[0009] Preferably, the functional freeze-dried tablets comprise, by weight, 1-5 parts ascorbic acid or its derivatives (e.g., 1, 2, 3, 4, or 5 parts), 2-10 parts humectant (e.g., 2, 3, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, or 10 parts, etc.), and 0.1-6 parts whitening agent (e.g., 0.1, 0.5...). 0.01-1 part pH adjuster (e.g., 0.01, 0.05, 0.1, 0.15, 0.2, 0.5, 0.7, 1 part, etc.), 10-30 parts lyophilization protectant (e.g., 10, 12, 15, 17, 19, 20, 22, 25, 27, 30 parts, etc.).

[0010] Preferably, the components in the freeze-drying protectant include, by weight, 0.1-1 parts of polyethylene glycol (e.g., 0.1 parts, 0.15 parts, 0.2 parts, 0.5 parts, 0.7 parts, 1 part, etc.), 0.1-1 parts of bis-PEG-18 methyl ether dimethylsilane (e.g., 0.1 parts, 0.15 parts, 0.2 parts, 0.5 parts, 0.7 parts, 1 part, etc.), and 10-30 parts of mannitol (e.g., 10 parts, 12 parts, 15 parts, 18 parts, 20 parts, 22 parts, 25 parts, 27 parts, 30 parts, etc.).

[0011] Preferably, the polyethylene glycol includes any one or a combination of at least two of PEG-800, PEG-2M, PEG-5M, PEG-7M, PEG-9M, PEG-14M, PEG-20M, PEG-23M, PEG-25M, PEG-45M, PEG-65M, PEG-90M, PEG-115M, and PEG-160M.

[0012] Preferably, the average relative molecular mass of the polyethylene glycol is 1000 kDa - 3000 kDa, for example, it can be 1012 kDa (PEG-23M), 1980 kDa (PEG-45M), or 2860 kDa (PEG-65M).

[0013] In this invention, the molecular weights of PEG-23M, PEG-45M, and PEG-65M are calculated based on the number of repeating units. For example, PEG-45M has n=45000, and its weight-average molecular weight is calculated to be 1980 kDa.

[0014] Preferably, the moisturizer comprises any one or a combination of at least two of sodium hyaluronate, butylene glycol, β-glucan, propylene glycol, glycerin, and pentanediol.

[0015] Preferably, the moisturizer is a combination of full-spectrum hyaluronic acid, low-molecular-weight sodium hyaluronate, and butylene glycol.

[0016] Preferably, the whitening agent includes any one or a combination of at least two of 4-butylresorcinol, phenylethylresorcinol, hexylresorcinol, arbutin, kojic acid, and tranexamic acid.

[0017] Preferably, the pH adjuster comprises any one of the following: a combination of citric acid and sodium citrate, a combination of disodium hydrogen phosphate and sodium dihydrogen phosphate, a combination of lactic acid and sodium lactate, or a combination of tartaric acid and sodium tartrate.

[0018] In a second aspect, the present invention provides a method for preparing the functional freeze-dried tablets as described in the first aspect, the method comprising: mixing ascorbic acid or its derivatives, a moisturizer, a whitening agent, and a pH adjuster, then mixing with a freeze-drying protectant, and freeze-drying to obtain the functional freeze-dried tablets.

[0019] Preferably, the mixing temperature is independently selected from 20-30°C (e.g., 20°C, 22°C, 24°C, 26°C, 28°C, 30°C, etc.).

[0020] All other specific point values ​​not listed above within the numerical ranges mentioned above can be selected and are all within the protection scope of this invention. For the sake of brevity, they will not be described in detail here.

[0021] Thirdly, the present invention provides the application of the functional freeze-dried tablets as described in the first aspect in the preparation of cosmetics.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] This invention creatively incorporates a freeze-drying protectant into freeze-dried tablets containing ascorbic acid or its derivatives. This improves the appearance of the freeze-dried tablets produced using freeze-drying molds, while also adjusting the overall skin feel and solubility, and maintaining the stability of the active ingredients. The freeze-drying protectant uses a combination of polyethylene glycol, bis-PEG-18 methyl ether dimethylsilane, and mannitol. These three components work synergistically to enhance the freeze-dried tablets' toughness and hardness while providing excellent smoothness, thus improving the user experience. Detailed Implementation

[0024] To further illustrate the technical means and effects of the present invention, the following describes the technical solution of the present invention in conjunction with preferred embodiments of the present invention. However, the present invention is not limited to the scope of the embodiments.

[0025] The full-spectrum hyaluronic acid used in this embodiment of the invention was purchased from Shandong Tiansheng Biotechnology Co., Ltd., and its Chinese name is sodium hyaluronate, while its trade name is SupremeHyal. ® Shunhua ® Low molecular weight sodium hyaluronate was purchased from Bloomage Biotechnology Co., Ltd., under the trade name Hybloom. TM Low molecular weight sodium hyaluronate (HA-TLM 20-40).

[0026] Example 1

[0027] This embodiment provides a functional freeze-dried tablet, and the raw materials used in its preparation are shown in Table 1:

[0028]

[0029] The preparation method is as follows:

[0030] Ascorbic acid, moisturizer, whitening agent, pH adjuster and water are mixed at 25°C and stirred evenly. Then, a freeze-drying protectant is added and stirred evenly at 25°C. The mixture is then filled into freeze-drying molds and freeze-dried for 24 hours to obtain functional freeze-dried tablets.

[0031] Example 2

[0032] This embodiment provides a functional freeze-dried tablet, and the raw materials used in its preparation are shown in Table 2:

[0033]

[0034] The preparation method is as follows:

[0035] Ascorbic acid, moisturizer, whitening agent, pH adjuster and water are mixed at 20°C and stirred evenly. Then, a freeze-drying protectant is added and stirred evenly at 20°C. The mixture is then filled into freeze-drying molds and freeze-dried for 24 hours to obtain functional freeze-dried tablets.

[0036] Example 3

[0037] This embodiment provides a functional freeze-dried tablet, and the raw materials used in its preparation are shown in Table 3:

[0038]

[0039] The preparation method is as follows:

[0040] Ascorbic acid, moisturizer, whitening agent, pH adjuster and water are mixed at 30°C and stirred evenly. Then, a freeze-drying protectant is added and stirred evenly at 30°C. The mixture is then filled into freeze-drying molds and freeze-dried for 24 hours to obtain functional freeze-dried tablets.

[0041] Example 4

[0042] This embodiment provides a functional lyophilized tablet. The only difference between this embodiment and Example 1 is that full-spectrum hyaluronic acid is not added. Instead, the missing amount of full-spectrum hyaluronic acid is allocated to low-molecular-weight sodium hyaluronate. All other conditions remain unchanged.

[0043] Example 5

[0044] This embodiment provides a functional freeze-dried tablet. The only difference between this embodiment and Example 1 is that low molecular weight sodium hyaluronate is not added. Instead, the missing amount of low molecular weight sodium hyaluronate is allocated to full-spectrum hyaluronic acid. All other conditions remain unchanged.

[0045] Example 6

[0046] This embodiment provides a functional lyophilized tablet. The preparation method differs from that in Example 1 only in that the PEG-45M fraction is replaced with PEG-800 (average relative molecular weight of 35 kDa), while all other conditions remain unchanged.

[0047] Example 7

[0048] This embodiment provides a functional lyophilized tablet. The preparation method differs from that in Example 1 only in that the PEG-45M fraction is replaced with PEG-115M (average relative molecular weight of 5060 kDa), while all other conditions remain unchanged.

[0049] Comparative Example 1

[0050] This comparative example provides a functional lyophilized tablet. The preparation method differs from that of Example 1 only in that PEG-45M is not added, and its reduced amount is proportionally allocated to bis-PEG-18 methyl ether dimethylsilane and mannitol, while other conditions remain unchanged.

[0051] Comparative Example 2

[0052] This comparative example provides a functional lyophilized tablet. The preparation method differs from that of Example 1 only in that bis-PEG-18 methyl ether dimethylsilane is not added, and the reduced amount of bis-PEG-18 methyl ether dimethylsilane is proportionally allocated to PEG-45M and mannitol, while other conditions remain unchanged.

[0053] Comparative Example 3

[0054] This comparative example provides a functional lyophilized tablet. The preparation method differs from that of Example 1 only in that mannitol is not added, and the reduced amount of mannitol is proportionally allocated to PEG-45M and bis-PEG-18 methyl ether dimethylsilane. All other conditions remain unchanged.

[0055] Comparative Example 4

[0056] This comparative example provides a functional lyophilized tablet. The only difference between this preparation method and Example 1 is that no lyophilization protectant is added. Instead, the reduced amount of lyophilization protectant is proportionally allocated to ascorbic acid, moisturizer, whitening agent, and pH adjuster. All other conditions remain unchanged.

[0057] Test Example 1

[0058] This test example evaluates the appearance of the lyophilized tablets of Examples 1-7 and Comparative Examples 1-4. Each group of lyophilized tablets was placed in a dry petri dish and deionized water was sprayed evenly onto the lyophilized tablets to examine their natural dissolution rate.

[0059] The results are shown in Table 4.

[0060]

[0061] The results showed that the functional lyophilized tablets designed in this invention have excellent appearance stability, a smooth surface that can form a uniform, glossy coating, and a fast dissolution rate. Changing the formulation of the lyophilization protectant will result in a slightly rougher surface and a decreased dissolution rate; without the addition of the lyophilization protectant, the surface of the lyophilized tablets is noticeably rough and uneven.

[0062] Test Example 2

[0063] This test example examines the appearance stability of the functional freeze-dried tablets from Examples 1-7 and Comparative Examples 1-4.

[0064] Each group of functional freeze-dried tablets was placed at room temperature (25℃) and at 48℃ for one month, respectively. The condition of each group of functional freeze-dried tablets was observed and scored. The lower the score, the worse the appearance of the freeze-dried tablets. The scoring criteria are as follows:

[0065] 8-10 points: No obvious changes in appearance; 4-7 points: Yellowing of varying degrees in appearance; 1-3 points: The freeze-dried tablets collapse or shrink.

[0066] The results are shown in Table 5.

[0067]

[0068] The functional freeze-dried tablets designed in this invention can maintain an excellent appearance after being placed at 25°C or 48°C for one month, and there will be no significant change compared with when they were freshly freeze-dried. If the compound of freeze-drying protectant is changed, the surface will turn yellow to varying degrees. If no freeze-drying protectant is added, the freeze-dried tablets will collapse / shrink within one month and will not be able to maintain a good shape.

[0069] Test Example 3

[0070] This test case examines the changes in vitamin C content of the lyophilized tablets from Examples 1-5 and Comparative Example 4 before and after being stored at 48°C for one month.

[0071] Sample preparation: The lyophilized tablets prepared in Examples 1-5 and Comparative Example 4 were divided into a control group and an accelerated group. The control group was directly mixed with deionized water at a mass ratio of 1:5000, and the initial vitamin C content was measured and denoted as Y0. The accelerated group was first placed at 48℃ for 30 days, and then deionized water was added at a mass ratio of 1:5000 and mixed thoroughly. The residual vitamin C content under these conditions was then measured and denoted as Y0. 30 .

[0072] Test method: The VC content in each group of test samples was obtained by referring to the first method "liquid chromatography" in GB 5009.86-2025 "National Food Safety Standard - Determination of Ascorbic Acid in Food".

[0073] Results Calculation: Based on the VC content in the test sample, the VC loss was calculated according to the following formula, and the results are shown in Table 6.

[0074] VC loss (%) = (Y0 - Y 30 ) / Y0×100%

[0075]

[0076] The results showed that the functional freeze-dried tablets prepared by this invention exhibited a vitamin C loss rate of less than 15% after being stored at 48°C for one month, demonstrating good stability. Changing the content of components in the humectant led to decreased stability, resulting in a reduction in vitamin C content; without the addition of a freeze-drying protectant, the vitamin C content decreased significantly.

[0077] The applicant declares that the technical solution of this invention is illustrated by the above embodiments, but this invention is not limited to the above embodiments, that is, it does not mean that this invention must rely on the above embodiments to be implemented. Those skilled in the art should understand that any improvements to this invention, equivalent substitutions of raw materials for the products of this invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of this invention.

[0078] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

[0079] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not describe the various possible combinations separately.

Claims

1. An effervescent lyophilized tablet containing a lyoprotectant, characterized in that, The functional lyophilized tablets include ascorbic acid or its derivatives, humectants, whitening agents, pH adjusters, and lyophilization protectants; The freeze-drying protectant comprises a combination of polyethylene glycol, bis-PEG-18 methyl ether dimethylsilane, and mannitol.

2. The functional freeze-dried tablets according to claim 1, characterized in that, The functional lyophilized tablets comprise, by weight, 1-5 parts ascorbic acid or its derivatives, 2-10 parts moisturizer, 0.1-6 parts whitening agent, 0.01-1 part pH adjuster, and 10-30 parts lyophilization protectant; The freeze-drying protectant comprises, by weight, 0.1-1 parts polyethylene glycol, 0.1-1 parts bis-PEG-18 methyl ether dimethylsilane, and 10-30 parts mannitol.

3. The functional freeze-dried tablets according to claim 1, characterized in that, The polyethylene glycol includes any one or a combination of at least two of PEG-800, PEG-2M, PEG-5M, PEG-7M, PEG-9M, PEG-14M, PEG-20M, PEG-23M, PEG-25M, PEG-45M, PEG-65M, PEG-90M, PEG-115M, and PEG-160M.

4. The functional freeze-dried tablets according to claim 1, characterized in that, The average relative molecular mass of the polyethylene glycol is 1000 kDa-3000 kDa.

5. The functional freeze-dried tablets according to claim 1, characterized in that, The moisturizer is a combination of full-spectrum hyaluronic acid, low-molecular-weight sodium hyaluronate, and butylene glycol.

6. The functional freeze-dried tablets according to claim 1, characterized in that, The whitening agent includes any one or a combination of at least two of 4-butylresorcinol, phenylethylresorcinol, hexylresorcinol, arbutin, kojic acid, and tranexamic acid.

7. The functional freeze-dried tablets according to claim 1, characterized in that, The pH adjuster includes any one of the following: a combination of citric acid and sodium citrate, a combination of disodium hydrogen phosphate and sodium dihydrogen phosphate, a combination of lactic acid and sodium lactate, or a combination of tartaric acid and sodium tartrate.

8. The method for preparing functional freeze-dried tablets according to any one of claims 1-7, characterized in that, The preparation method includes: mixing ascorbic acid or its derivatives, moisturizers, whitening agents, and pH adjusters, then mixing with a lyophilization protectant, and freeze-drying to obtain the functional lyophilized tablets.

9. The preparation method according to claim 8, characterized in that, The mixing temperatures are each independently selected from 20-30°C.

10. The use of the functional freeze-dried tablets according to any one of claims 1-7 in the preparation of cosmetics.

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