Allicin oleogel as well as preparation method and application thereof

Abstract

The invention discloses allicin oleogel as well as a preparation method and application thereof, and belongs to the technical field of medicines. The allicin oleogel is prepared from the following raw materials: allicin, an oil phase, a gelator and a surfactant, the gelator comprises beeswax and / or fruit wax; the surfactant comprises one or more of caprylic / capric polyethylene glycol glyceride, Tween 20 and polyglycerol fatty acid ester. The gel factor forms oil gel through crystal self-assembly, allicin is solidified and intercepted in the oil gel, the gel factor is optimized, and a surfactant is used in a matched manner, so that a release behavior similar to that of a mixed solution of free allicin and an oil phase can be obtained, and the transdermal release rate is improved. The allicin oil gel can effectively entrap allicin, cover the peculiar smell of the allicin and improve the stability of the allicin, and through abdominal transdermal administration, the medicine accumulation amount in subcutaneous adipose tissues is remarkably increased, and the treatment effect on obesity and complications thereof can be improved.

Description

Technical Field

[0001] The present application relates to the field of medical technology, and in particular to allicin oil gel and its preparation method and application. Background Art

[0002] Obesity, as a metabolic disease, is often accompanied by insulin resistance, non-alcoholic fatty liver disease, and dyslipidemia, in addition to significant weight gain. Currently, common medications for the clinical treatment of obesity include lipase inhibitors, appetite suppressants, and drugs based on nutrient-stimulating hormones. These drugs are prone to causing adverse gastrointestinal reactions, constipation, nausea, and diarrhea. Therefore, there is an urgent need to develop new, safe, and effective clinical treatments for obesity.

[0003] Adipose tissue is the primary site of fat synthesis, storage, and hydrolysis, playing a crucial role in energy metabolism. Functionally, it can be divided into energy-storing white adipose tissue (WAT) and energy-consuming brown and beige adipose tissue (BAT). In obese individuals, white adipose tissue can account for up to 50% of body weight, while the proportion of energy-consuming brown adipose tissue is significantly reduced. Therefore, promoting the browning of white adipose tissue to beige adipose tissue is a promising strategy for reversing energy imbalance and promoting weight loss.

[0004] Allicin, a diallyl trisulfide, is an active volatile oil extracted from the bulb (head) of the Allium sativum plant, Allium genus. Literature reports suggest that it can enhance energy metabolism by promoting the browning of white fat, thereby exerting therapeutic effects on obesity. However, in vitro studies have shown that allicin regulates genes involved in energy metabolism in adipocytes at concentrations as high as 10-100 µM. Traditional oral allicin requires gastrointestinal absorption and bloodstream distribution to reach adipose tissue to exert its effects. However, allicin is easily degraded in the gastrointestinal tract and has a plasma half-life of less than 1 minute. Therefore, oral allicin products are unlikely to produce a substantial weight loss effect. Topical allicin can directly penetrate the skin barrier and enter subcutaneous adipose tissue, effectively avoiding gastrointestinal degradation and a short plasma half-life. However, allicin has a strong pungent odor, and weight management is a long-term treatment requiring repeated dosing, resulting in poor acceptance of topical allicin products. Therefore, developing new dosage forms of allicin with reduced odor is crucial for the treatment of obesity with topical allicin. Summary of the Invention

[0005] Based on this, the main purpose of this application is to provide an allicin oil gel suitable for external use in the treatment of obesity. The allicin oil gel is prepared using allicin, an oil phase, a gelling factor and a surfactant. The allicin oil gel can effectively encapsulate allicin and mask the odor of allicin, improve the stability of allicin, and be administered transdermally in the abdomen, significantly increasing the drug accumulation in subcutaneous adipose tissue, thereby improving the therapeutic effect on obesity and its complications.

[0006] In a first aspect of the present application, a garlic oil gel is provided, comprising the following raw materials: allicin, an oil phase, a gelling factor and a surfactant; the gelling factor comprises beeswax and / or fruit wax; the surfactant comprises one or more of caprylic acid capric acid macrogol glyceride, Tween 20 and polyglycerol fatty acid ester.

[0007] In some embodiments, the oil phase comprises one or more of vegetable oil, dimethicone, petrolatum, liquid fatty alcohol, and liquid fatty acid.

[0008] In some embodiments, the allicin oil gel comprises the following raw materials, in parts by weight: 0.5-5 parts of allicin, 60-100 parts of oil phase, 4-30 parts of gelling factor and 5-15 parts of surfactant.

[0009] The second aspect of the present application provides a method for preparing the allicin oil gel described in the first aspect, comprising the following steps:

[0010] heating the gel factor until it is melted and mixing it with the oil phase to form a first mixture;

[0011] mixing the first mixture, the allicin, and the surfactant to form a second mixture;

[0012] The second mixture is cooled and solidified to form the allicin oil gel.

[0013] In some embodiments, the heating conditions include: heating temperature 65-90° C.; heating time 5-30 min.

[0014] In some embodiments, the cooling and solidification conditions include: cooling to room temperature.

[0015] The third aspect of the present application provides the use of the allicin oil gel described in the first aspect in the preparation of a drug for external use to treat obesity or a drug delivery system.

[0016] In some embodiments, the treatment of obesity comprises at least one of reducing body weight, improving insulin resistance, inhibiting liver weight gain, inhibiting non-alcoholic fatty liver disease formation, and inhibiting subcutaneous adipose tissue inflammation.

[0017] The fourth aspect of the present application provides a drug combination comprising the allicin oil gel described in the first aspect.

[0018] In some embodiments, the pharmaceutical combination further comprises other active ingredients that target adipocytes.

[0019] In some embodiments, the other active ingredients targeting adipocytes include one or more of berberine, hypericin, capsaicin, resveratrol, and perforin.

[0020] Beneficial effects of this application:

[0021] 1. This application prepares an allicin oleogel from allicin, an oil phase, a gelling agent, and a surfactant. The gelling agent forms the oleogel through crystal self-assembly, solidifying and entrapping the allicin within the oleogel. By optimizing the gelling agent and using a surfactant, a release behavior similar to that of a mixed solution of free allicin and the oil phase is achieved, significantly improving transdermal drug delivery. This allicin oleogel effectively entraps allicin, masks its odor, and improves its stability.

[0022] 2. The allicin oil gel of the present application is administered transdermally in the abdomen, which significantly increases the drug accumulation in the subcutaneous fat tissue and can improve the treatment effect of obesity and its complications.

[0023] 3. The allicin oil gel of this application can effectively reduce the weight of mice with high-fat diet-induced obesity to normal, improve insulin resistance, inhibit liver weight gain and the development of non-alcoholic fatty liver disease in mice with high-fat diet-induced obesity, and inhibit inflammatory infiltration of subcutaneous adipose tissue in mice with high-fat diet-induced obesity (specifically, it inhibits the inflammatory infiltration of M1 macrophages in subcutaneous adipose tissue and increases the number of M2 macrophages). This product has promising development and application prospects in the treatment of high-fat diet-induced obesity and its complications. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the following briefly introduces the drawings required for the embodiments or the prior art description. The drawings are only used to illustrate the preferred embodiments and are not considered to limit the present application. The same reference symbols are used throughout the drawings to represent the same components. In the drawings:

[0025] Figure 1 This is the appearance of the allicin oil gel of Example 1;

[0026] Figure 2 The electronic nose test results of the taste-masking effect of allicin oil gel on allicin, W1W is sulfide, W2W is organic sulfide, the ordinate is the content, Blank is the oil gel without allicin; Free drug is the mixed solution of free allicin and linseed oil; OG is the allicin oil gel of Example 1; *, **, *** represent p < 0.05, p < 0.01, and p < 0.001, respectively;

[0027] Figure 3 Soybean oil solutions containing different amounts of allicin were used for odor evaluation in Examples and Comparative Examples.

[0028] Figure 4 These are microscopic morphologies of the allicin oil gel of Example 1, wherein A is a bright field microscopic image, B is a polarized light field microscopic image, C is a Nile red staining image, D is a scanning electron microscope image, and F is a bright field image of a mixed solution of allicin and linseed oil without beeswax.

[0029] Figure 5 This is the infrared spectrum of the allicin oil gel of Example 1, Allicin is allicin, and Allicin+Beeswax+Flaxseed oil is the oil gel of Comparative Example 2 without adding surfactant;

[0030] Figure 6 This is a graph showing the content stability of the allicin oil gel (OG) of Example 1 at room temperature;

[0031] Figure 7 : is the transdermal release diagram of allicin oil gel, wherein Free drug is a mixed solution of free allicin and linseed oil, OG is the allicin oil gel of Example 1, and OGGM is the oil gel prepared by replacing beeswax with monostearate glyceryl in Comparative Example 1;

[0032] Figure 8 Figure 3 is a graph showing the accumulation of subcutaneous fat in vivo after allicin oil gel administration, wherein "Free drug" refers to the transdermal administration of a solution of free allicin and linseed oil, and "OG" refers to the transdermal administration of the allicin oil gel of Example 1; "Free drug (oral)" refers to the oral administration of a solution of free allicin and linseed oil, and "OGO" refers to the oral administration of the allicin oil gel of Example 1. In this figure, A represents the change in allicin concentration in subcutaneous adipose tissue, B represents the area under the curve of allicin concentration in subcutaneous adipose tissue, C represents the change in allicin concentration in visceral adipose tissue, and D represents the area under the curve of allicin concentration in visceral adipose tissue.

[0033] Figure 9 Figure 1 is a graph showing the effect of allicin oil gel on weight loss in obese mice, wherein NFD represents mice fed a normal diet; HFD represents obese mice modeled on a high-fat diet; and OG represents obese mice fed a high-fat diet that were treated with the allicin oil gel in Example 1 through the abdominal transdermal route.

[0034] Figure 10 Figure 1 is a graph showing the effect of allicin oil gel on improving insulin resistance in obese mice, wherein NFD is a mouse fed a normal diet; HFD is an obese mouse model induced by a high-fat diet; and OG is an obese mouse fed a high-fat diet that was treated with the allicin oil gel of Example 1.

[0035] Figure 11 Figure 1 shows the effect of allicin oil gel on the liver weight gain and liver appearance of obese mice. NFD is a normal diet-fed mouse model; HFD is a high-fat diet-fed obese mouse model; and OG is a high-fat diet-fed obese mouse model treated with the allicin oil gel of Example 1.

[0036] Figure 12 Figure 3 is a flow cytometric analysis of macrophage typing in subcutaneous adipose tissue of mice after topical treatment with allicin oil gel, wherein NFD represents mice fed a normal diet; HFD represents obese mice modeled with a high-fat diet; OG represents obese mice fed a high-fat diet treated with the allicin oil gel of Example 1; *, **, *** represent p<0.05, p<0.01, and p<0.001, respectively. DETAILED DESCRIPTION

[0037] To make the objectives, technical solutions, and advantages of this application more clear and to provide a more thorough and comprehensive understanding of the disclosure of this application, the following will provide a clear and complete description of the technical solutions of this application in conjunction with the specific embodiments of this application and the corresponding drawings. The described embodiments are only part of the embodiments of this application, not all of them.

[0038] The following is a detailed description of the implementation of this application in conjunction with the accompanying drawings. This embodiment is implemented based on the technical solution of this application, and provides a detailed implementation method and specific operation process, but the scope of protection of this application is not limited to the following embodiment.

[0039] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which this application pertains. The terms used herein in the specification of this application are for the purpose of describing specific embodiments only and are not intended to limit this application.

[0040] the term

[0041] Unless otherwise specified or incompatible herewith, the terms and phrases used herein shall have the following meanings:

[0042] In this application, "a plurality of" or "a plurality of" refers to a number greater than or equal to 2 unless otherwise specified. For example, "one or more" or "at least one" means one or more than or equal to two.

[0043] In this application, "further", "particularly" and the like are used for descriptive purposes to indicate differences in content, but should not be understood as limiting the scope of protection of this application.

[0044] In this application, the technical features described in an open manner include closed technical solutions composed of the listed features, and also include open technical solutions containing the listed features.

[0045] In this application, when referring to a numerical interval (i.e., a numerical range), unless otherwise specified, the distribution of the optional numerical values within the numerical interval is deemed to be continuous and includes the two numerical endpoints of the numerical interval (i.e., the minimum and maximum values), as well as every numerical value between these two numerical endpoints. Unless otherwise specified, when a numerical interval refers only to integers within the numerical interval, it includes the two endpoint integers of the numerical range, as well as every integer between the two endpoints, which is equivalent to directly listing every integer. When multiple numerical ranges are provided to describe a feature or characteristic, these numerical ranges can be combined. In other words, unless otherwise specified, the numerical ranges disclosed herein should be understood to include any and all subranges included therein. The "numerical value" in the numerical interval can be any quantitative value, such as a number, percentage, ratio, etc. "Numerical interval" allows for a broad range of numerical interval types including percentage intervals, ratio intervals, and ratio intervals.

[0046] Unless otherwise specified, the percentage contents mentioned in this application refer to mass percentage for solid-liquid mixture and solid-solid mixture, and refer to volume percentage for liquid-liquid mixture.

[0047] Unless otherwise specified, the percentage concentrations mentioned in this application refer to the final concentration, which refers to the percentage in the system after the addition of the component.

[0048] In this application, unless otherwise specified, temperature parameters may be either constant temperature or fluctuating within a certain temperature range. It should be understood that constant temperature processing allows for temperature fluctuations within the precision range of instrument control. Fluctuations within ranges such as ±5°C, ±4°C, ±3°C, ±2°C, and ±1°C are permitted.

[0049] In this application, when referring to a range of units, if only the right endpoint is followed by the unit, it means that the units of the left and right endpoints are the same. For example, 2-5h means that the units of the left endpoint "2" and the right endpoint "5" are both hours.

[0050] As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items.

[0051] In this application, temperature parameters, unless otherwise specified, allow for both constant temperature treatment and treatment within a certain temperature range. The constant temperature treatment allows for temperature fluctuations within the precision range of instrument control. The room temperature referred to in this application refers to 0-40°C, preferably 10-35°C, and more preferably 20-30°C.

[0052] In a first aspect, the present application provides an external allicin oil gel, comprising the following raw materials: allicin, an oil phase, a gelling factor, and a surfactant; the gelling factor comprises beeswax and / or fruit wax; the surfactant comprises one or more of caprylic acid capric acid macrogol glyceride, Tween 20, and polyglycerol fatty acid esters.

[0053] Oleogel is a thermoreversible organogel prepared from an oil phase (such as unsaturated fatty acids) and a small amount of gelling agent. It is semisolid at room temperature and can dissolve or encapsulate drug molecules within its internal oil phase. Drug release can be controlled by adjusting the amount and type of gelling agent. Oleogels exhibit enhanced biomembrane diffusion and permeability, which facilitates drug absorption through the skin and mucous membranes. They also prevent drug degradation in aqueous environments, thereby improving drug stability. As a novel drug delivery system, oleogels have garnered extensive attention and research in recent years, demonstrating significant potential for application.

[0054] This application prepares an allicin oleogel from allicin, an oil phase, a gelling agent, and a surfactant. The gelling agent forms the oleogel through crystal self-assembly, solidifying and trapping the allicin within the oleogel. By optimizing the gelling agent and using a surfactant in combination, a release behavior similar to that of a mixed solution of free allicin and the oil phase is achieved, with improved transdermal efficiency. This allicin oleogel effectively entraps allicin, masks its odor, and improves its stability. Transdermal administration of this allicin oleogel via the abdomen significantly increases drug accumulation in subcutaneous adipose tissue, enhancing the therapeutic efficacy of obesity and its complications.

[0055] In the present application, the specific type of the oil phase is not particularly limited; optionally, the oil phase includes one or more of vegetable oil, dimethyl silicone oil, petrolatum, liquid fatty alcohol and liquid fatty acid; further optionally, the vegetable oil includes at least one of linseed oil, camellia oil, corn oil, peanut oil and soybean oil.

[0056] In a specific example, the allicin oil gel comprises the following raw materials, in parts by weight: 0.5-5 parts of allicin, 60-100 parts of oil phase, 4-30 parts of gelling factor and 5-15 parts of surfactant.

[0057] Specifically, the amount of allicin can be 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5 or 5 parts; the amount of the oil phase can be 60, 65, 70, 75, 80, 83, 85, 90, 95 or 100 parts; the amount of the gelling factor is preferably 4-10 parts, specifically 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or 30 parts; the amount of the surfactant can be 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 parts.

[0058] In a specific example, the mass ratio of the oil phase to the surfactant is 1-12:1, for example, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, etc.

[0059] In a specific example, the allicin oil gel includes the following raw materials, calculated in parts by weight: 1 part of allicin, 83 parts of oil phase, 6 parts of gelling factor and 10 parts of surfactant.

[0060] The second aspect of the present application provides a method for preparing the allicin oil gel described in the first aspect, comprising the following steps:

[0061] heating the gel factor until it is melted and mixing it with the oil phase to form a first mixture;

[0062] mixing the first mixture, the allicin, and the surfactant to form a second mixture;

[0063] The second mixture is cooled and solidified to form the allicin oil gel.

[0064] In the present application, the gelling factor and the oil phase are first mixed to obtain a liquid first mixture, which is then mixed with allicin and a surfactant to achieve good dispersion of the allicin and the surfactant. After cooling and solidification, the gelling factor forms an oil gel through crystal self-assembly, and the allicin is solidified and trapped in the oil gel.

[0065] It is understandable that in the above preparation method, the mixing step can achieve uniform mixing of the raw materials, and the specific conditions are not particularly limited.

[0066] In a specific example, the heating conditions include: heating temperature 65-90°C, for example, 65°C, 70°C, 75°C, 80°C, 85°C, 90°C, etc.; heating time 5-30min, for example, 5min, 10min, 15min, 20min, 25min, 30min, etc.

[0067] In a specific example, before the step of mixing the first mixture, the allicin and the surfactant, the step of cooling the first mixture to 50-60°C (e.g., 50°C, 52°C, 54°C, 56°C, 58°C, 60°C) is also included.

[0068] In a specific example, the cooling and solidification conditions include: cooling to room temperature.

[0069] The third aspect of the present application provides the use of the allicin oil gel described in the first aspect in the preparation of a method for treating obesity.

[0070] The allicin oil gel of the present application can effectively encapsulate allicin and mask its odor, thereby improving its stability. Through topical administration, it significantly increases the accumulation of the drug in subcutaneous adipose tissue, thereby enhancing the therapeutic effect on obesity and its complications. Furthermore, the allicin oil gel can also be used for drug delivery, particularly the delivery of volatile oils.

[0071] In a specific example, the treatment of obesity includes at least one of reducing body weight, improving insulin resistance, inhibiting liver weight gain, inhibiting the formation of non-alcoholic fatty liver, and inhibiting inflammation of subcutaneous adipose tissue.

[0072] It can be understood that external use refers to the administration of drugs through the skin, mucous membranes, oral cavity, nasal cavity, rectum and other body surface parts, and transdermal administration is optional.

[0073] The fourth aspect of the present application provides a medicine comprising the allicin oil gel described in the first aspect.

[0074] In a specific example, the drug further includes other active ingredients targeting fat cells; specifically, the other active ingredients targeting fat cells include one or more of berberine, hypericin, capsaicin, resveratrol and perforin.

[0075] Unless otherwise specified, the raw materials used in the following experiments can be purchased from the market.

[0076] The raw materials used in the examples and comparative examples are exemplified as follows:

[0077] Linseed oil: Product No. L304664, purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.;

[0078] Beeswax: Product No. B113018, purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.

[0079] Fruit wax: Product No. B240204, purchased from Guangzhou Ruishi Biotechnology Co., Ltd.

[0080] Caprylic / capric macrogol glycerides: Product No. G304777, purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.;

[0081] Polyglycerol 10-distearate: Product No. S-Faces-1002P, purchased from Japan Surfactant Industry Co., Ltd.

[0082] Vaseline: Product No. V820408, purchased from Shanghai MacLean Biochemical Technology Co., Ltd.

[0083] Soybean oil: Product No. S110245, purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.

[0084] The following are specific examples.

[0085] Example 1

[0086] Preparation of garlic oil gel:

[0087] The recipe is as follows:

[0088] 1 part of allicin, 83 parts of oil phase (linseed oil), 6 parts of gelling factor (beeswax) and 10 parts of surfactant (caprylic acid capric acid macrogol glyceride).

[0089] The preparation process is as follows:

[0090] 1) heating the gelling agent at 70° C. for 5 minutes until melted, and mixing with the oil phase until uniform, to form a first mixture;

[0091] 2) Cooling the first mixture to 55° C., adding allicin and a surfactant and mixing uniformly to form a second mixture;

[0092] 3) Cooling and solidifying the second mixture to form an allicin oil gel.

[0093] The prepared allicin oil gel is a light yellow gel, such as Figure 1 shown.

[0094] Example 2

[0095] The recipe is as follows:

[0096] 1 part of allicin, 80 parts of oil phase (medium chain triglycerides), 6 parts of gelling factor (fruit wax) and 10 parts of surfactant (polyglycerol 10-distearate).

[0097] The preparation process is as follows:

[0098] 1) heating the gelling factor at 65°C for 10 minutes until melted, and mixing with the oil phase until uniform, to form a first mixture;

[0099] 2) Cooling the first mixture to 55° C., adding allicin and a surfactant and mixing uniformly to form a second mixture;

[0100] 3) Cooling and solidifying the second mixture to form an allicin oil gel.

[0101] Example 3

[0102] The recipe is as follows:

[0103] 1 part of allicin, 85 parts of oil phase (vaseline), 8 parts of gelling factor (beeswax) and 10 parts of surfactant (Tween-20).

[0104] The preparation process is as follows:

[0105] 1) heating the gelling factor at 65°C for 10 minutes until melted, and mixing with the oil phase until uniform, to form a first mixture;

[0106] 2) Cooling the first mixture to 55° C., adding allicin and a surfactant and mixing uniformly to form a second mixture;

[0107] 3) Cooling and solidifying the second mixture to form an allicin oil gel.

[0108] Comparative Example 1

[0109] Except that glyceryl monostearate was used instead of beeswax, the rest was the same as in Example 1.

[0110] Comparative Example 2

[0111] Except for not adding surfactant, the rest is the same as Example 2.

[0112] Comparative Example 3

[0113] Except for not adding surfactant and gel factor, the rest is the same as Example 1.

[0114] Test Case

[0115] An allicin-free oil gel (same as Example 1 except for the absence of allicin) and a free allicin and linseed oil mixed solution (prepared by mixing 1 part allicin with 83 parts linseed oil, Free Drug) were prepared for comparison, and the properties of the allicin oil gel were analyzed.

[0116] Test Example 1 Basic physical property test of garlic oil gel

[0117] (1) Odor masking characteristics

[0118] 1.0 g of the allicin oil gel of Example 1, the allicin-free oil gel, and the mixed solution of free allicin and linseed oil were respectively taken in 50 mL centrifuge tubes. After standing at room temperature for 0.5 h, the electronic nose was used for measurement with a measurement time of 60 s and a cleaning time of 60 s.

[0119] like Figure 2 As shown, the allicin oil gel (OG) prepared in Example 1 significantly masked the odors of sulfide W1W and organosulfide W2W. The content of sulfide W1W and organosulfide W2W in the OG was similar to that of the allicin-free oil gel (Blank), and significantly higher than that of the mixed solution of free allicin and linseed oil (Free drug). This indicates that the allicin oil gel prepared in Example 1 effectively masked the odor of allicin.

[0120] (2) Odor score

[0121] like Figure 3As shown, a series of soybean oil solutions containing varying allicin contents (with allicin to soybean oil mass ratios of 1 / 100, 1 / 300, 1 / 600, 1 / 900, 1 / 1200, and 1 / 1500, respectively, w / w) were prepared as standard odor evaluation cards. A concentration of 1 / 100 indicated a distinct garlic odor, 1 / 600 indicated a slight garlic odor, and 1 / 1200 indicated no distinct garlic odor. Subsequently, 30 volunteers were asked to evaluate the garlic odor of Example 1 and Comparative Examples 1-3 using a sensory evaluation method. Specifically, the volunteers compared the odors of Example 1 and Comparative Examples 1-3 with the soybean oil solutions containing varying allicin contents. Ultimately, the soybean oil solution containing allicin that most closely matched the odor evaluation standard card was identified. This was used as a basis for determining the differences in the allicin masking effectiveness of the various systems.

[0122] In Example 1, the allicin odor corresponded to 1 / 1200, in Comparative Example 1, the allicin odor corresponded to 1 / 900; in Comparative Example 2, the allicin odor corresponded to 1 / 900; and in Comparative Example 3, the allicin odor was between 1 / 600 and 1 / 900. This shows that the use of gelling agents and surfactants can effectively encapsulate allicin and mask the allicin odor, and the specific type of gelling agent has a significant impact, with beeswax / fruit wax having improved odor-masking effects.

[0123] (3) Micromorphological analysis

[0124] An appropriate amount of the hot solution of the allicin oil gel sample of Example 1 was dropped onto a glass slide, a cover slip was lightly pressed on it, and the sample was left at room temperature for 24 hours. The microscopic morphology of the oil gel was then observed under an optical microscope and an optical microscope equipped with a polarized lens. The oil phase was dyed with Nile red dye to prepare a dyed allicin oil gel (with the same composition as in Example 1 except for the Nile red dye). An appropriate amount of the hot solution of the dyed allicin oil gel sample was dropped onto a glass slide, a cover slip was lightly pressed on it, and the sample was wrapped with tin foil and placed in a refrigerator at 4° C. for 24 hours to form a gel. The sample was then observed under a fluorescence microscope.

[0125] like Figure 4As shown in the figure, A is a brightfield microscopic image, B is a polarized light microscopic image, C is a Nile red staining image, D is a scanning electron micrograph, and F is a brightfield image of a mixed solution of free allicin and linseed oil. The brightfield image shows uniform dispersion of fibrous beeswax. Further observation of the internal structure using a polarized light microscope reveals that the crystalline structure of beeswax is evenly distributed within the oleogel, consistent with the brightfield observation results. To investigate the formation of the oleogel, the oil phase was stained with Nile red and observed under a fluorescence microscope. The overall background of the oleogel appears the color of the dye, while the beeswax is black, indicating that the oil phase accounts for the vast majority of the oleogel and that the beeswax is evenly distributed within the oil phase. This is likely due to the beeswax forming a three-dimensional gel network structure that entraps the oil phase. The scanning electron micrograph shows that the resulting oleogel has a smooth surface, resulting in a non-grainy feel when applied.

[0126] (4) Fourier transform infrared spectroscopy

[0127] Appropriate amounts of the allicin oil gel sample of Example 1, the oil gel without surfactant (the same as Example 1 except that no surfactant was added, all the other ingredients were allicin + beeswax + flaxseed oil), and allicin were placed in an infrared spectrometer for detection, with the scanning temperature set at 25°C and the wavelength range of 500-4000 cm -1 .

[0128] like Figure 5 As shown in the figure, after allicin forms oil gel, its carbon-sulfur characteristic peak, sulfur-sulfur characteristic peak and sulfur-oxygen characteristic peak shift, indicating that there is a non-covalent interaction between allicin and the gel matrix.

[0129] (5) Analysis of the stability of allicin oil gel

[0130] The allicin oil gel prepared in Example 1 was placed at room temperature, and the changes in the allicin content were detected by high performance liquid chromatography at different time points.

[0131] like Figure 6 As shown in the results, the allicin oil gel had good stability and no obvious degradation was observed within 37 days.

[0132] (6) In vitro transdermal release of allicin oil gel

[0133] Appropriate amounts of samples (3 samples per group) of allicin oleogel (OG) from Example 1, a mixed solution of free allicin and linseed oil (Freedrug), and comparative example 1 (OGGM) were weighed to investigate the in vitro transdermal release of the allicin oleogel. A Franz diffusion cell was used with the allicin oleogel or the mixed solution of free allicin and linseed oil in the upper chamber and medium-chain triglycerides in the lower chamber. The mixture was stirred at 150 rpm and maintained at 32°C. Samples were taken from the lower chamber at 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours. The allicin content at each time point was determined by high-performance liquid chromatography to evaluate the transdermal release of the oleogel.

[0134] like Figure 7 As shown, the allicin oil gel of Example 1 can smoothly release allicin and exhibits a release behavior similar to that of a mixed solution of free allicin and linseed oil. In addition, it has a higher transdermal release rate than the mixed solution of free allicin and linseed oil and the allicin oil gel of Comparative Example 1. In addition, the higher transdermal release rate of the allicin oil gel of Example 1 may be due to the penetration-promoting effect of the surfactant present in the oil gel.

[0135] Test Example 2: External application of allicin oil gel promotes the accumulation of allicin in subcutaneous fat.

[0136] The allicin oil gel of Example 1 with the same allicin content and a mixed solution of free allicin and linseed oil were administered orally and topically to mice, respectively, to study the effect of promoting the accumulation of allicin in subcutaneous fat. Among them, the operation of the topical group is as follows: a dose of 150 mg / kg was applied to the abdomen of mice (3 mice per group), and subcutaneous fat tissue was taken at 0.5, 1, 3, 6, and 12 hours, and 10 times the amount of methanol was added and homogenized. The change in the content of allicin was detected by high performance liquid chromatography. The topical group of Example 1 was recorded as OG, and the topical application group of the mixed solution of free allicin and linseed oil was recorded as Free drug; the operation of the oral group is as follows: a dose of 150 mg / kg was administered to mice by gavage (3 mice per group), and subcutaneous fat tissue was taken at 0.5, 1, 3, 6, and 12 hours, and 10 times the amount of methanol was added and homogenized. The change in the content of allicin was detected by high performance liquid chromatography. The topical group of Example 1 was recorded as OGO, and the topical application group of the mixed solution of free allicin and linseed oil was recorded as Free drug (oral).

[0137] like Figure 8As shown, no drug accumulation was detected in the subcutaneous fat of animals in the oral administration groups (free drug (oral) and OG). Allicin was not detected in either white adipose tissue (sWAT) or visceral white adipose tissue (eWAT). In contrast, allicin was detected in the fat of the topical administration groups (free drug and OG). The topical administration group (OG) significantly increased allicin accumulation in sWAT and eWAT compared to the group (free drug) that applied a mixed solution of free allicin and linseed oil. Specifically, the OG group had the highest allicin accumulation in sWAT, an 8.08-fold increase compared to the free drug group; the OG group also had a 7.05-fold increase in eWAT compared to the free drug group. Therefore, the total amount of allicin delivered to adipose tissue by OG was 7.62-fold higher than that of the free drug group. Topical application of allicin oil gel significantly increased drug accumulation in adipose tissue.

[0138] Test Example 3 Effect of in vivo treatment of obesity and its complications

[0139] C57BL / 6J mice aged 4-6 weeks were selected and fed a high-fat diet. When their body weight differed by 30% from that of mice fed a normal diet (NFD), they were randomly divided into a model group (HFD) and an allicin oil gel group (OG), with 8 mice in each group. The allicin oil gel group received a daily abdominal application of 30 mg / kg of the allicin oil gel of Example 1, while the model and normal groups received PBS solution. Body weights were measured weekly. During the dosing period, the allicin oil gel and model groups continued to maintain a high-fat diet, while the normal group continued to maintain a normal diet.

[0140] (1) Anti-obesity effect of allicin oil gel

[0141] The method is to measure the body weight of mice weekly. Figure 9 As shown in the figure, it can be seen that allicin oil gel significantly reduced the weight of obese mice induced by a high-fat diet. After one week of treatment, the weight of the allicin oil gel group dropped to the same level as that of the normal group, and no weight rebound was found during the administration period. It can be seen that allicin oil gel has a good anti-obesity effect when administered transdermally through the abdomen.

[0142] (2) Effect of garlic oil gel on improving insulin resistance

[0143] The method is to intraperitoneally inject insulin (0.7 IU / kg) into mice after fasting for 4 hours, and use blood glucose to measure the blood glucose changes of mice at 0, 15, 30, 60, and 120 minutes, with 8 mice in each group.

[0144] like Figure 10As shown, after intraperitoneal injection of insulin, the blood sugar level in the normal group dropped rapidly and stabilized; while in the model group, due to insulin resistance caused by obesity, the blood sugar level dropped slowly and the drop was small, and the blood sugar level remained at a higher level; the blood sugar level of mice in the allicin oil gel group showed a trend similar to that of the normal group, indicating that allicin oil gel significantly improved the insulin resistance caused by obesity.

[0145] (3) Allicin oil gel improves non-alcoholic fatty liver disease caused by obesity

[0146] The method is to kill the mice, weigh the liver of the mice and take pictures of the liver, with 8 mice in each group.

[0147] like Figure 11 As shown, obesity causes an increase in mouse liver weight. The liver weight of the allicin oil gel group was significantly lower than that of the model group and returned to the same level as the normal group. From the photos of the mouse livers, it can be seen that obesity-induced non-alcoholic fatty liver disease causes the mouse liver to appear light white (caused by lipid accumulation) and enlarged. However, allicin oil gel significantly inhibits the formation of non-alcoholic fatty liver disease caused by liver lipid accumulation.

[0148] (4) Allicin oil gel inhibits inflammatory infiltration of adipose tissue

[0149] The method is to separate the subcutaneous adipose tissue of mice (3 mice in each group) at the end of the experiment, stain it with flow dye, and use flow cytometry to detect the expression of CD86 and CD206 in the subcutaneous adipose tissue.

[0150] like Figure 12 As shown, a high-fat diet induces chronic inflammatory infiltration in subcutaneous adipose tissue, leading to an increase in CD86-labeled M1 macrophages and a decrease in CD206-labeled M2 macrophages in the model group compared to mice fed a normal diet. However, the allicin oil gel group significantly suppressed the number of CD86-labeled M1 macrophages and increased the number of CD206-labeled M2 macrophages. This suggests that allicin oil gel effectively inhibits inflammatory infiltration in adipose tissue.

[0151] The technical features of the above-mentioned embodiments can be combined arbitrarily. In order to make the description concise, not all possible combinations of the technical features in the above-mentioned embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0152] The above-described embodiments merely represent several implementation methods of the present application. While the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that a person skilled in the art could make various modifications and improvements without departing from the spirit of the present application, all of which fall within the scope of protection of the present application. Therefore, the scope of protection of the present patent application shall be determined by the appended claims.

Claims

1. A garlic oil gel, characterized in that The invention comprises the following raw materials: allicin, oil phase, gelling factor and surfactant; the gelling factor comprises beeswax and / or fruit wax; the surfactant comprises one or more of caprylic acid capric acid macrogol glyceride, Tween 20 and polyglycerol fatty acid ester.

2. The allicin oil gel according to claim 1, wherein The oil phase includes one or more of vegetable oil, dimethyl silicone oil, vaseline, liquid fatty alcohol and liquid fatty acid.

3. The allicin oil gel according to any one of claims 1 to 2, wherein The allicin oil gel comprises the following raw materials in parts by weight: 0.5-5 parts of allicin, 60-100 parts of oil phase, 4-30 parts of gelling factor and 5-15 parts of surfactant.

4. The method for preparing the allicin oil gel according to any one of claims 1 to 3, wherein The steps include: heating the gel factor until it is melted and mixing it with the oil phase to form a first mixture; mixing the first mixture, the allicin, and the surfactant to form a second mixture; The second mixture is cooled and solidified to form the allicin oil gel.

5. The preparation method according to claim 4, wherein The heating conditions include: heating temperature 65-90°C; heating time 5-30min; And / or, the cooling and solidification conditions include: cooling to room temperature.

6. Use of the allicin oil gel according to any one of claims 1 to 3 in preparing a drug for external use in treating obesity or a drug delivery system.

7. The use according to claim 6, characterized in that The treatment of obesity includes at least one of reducing body weight, improving insulin resistance, inhibiting liver weight gain, inhibiting the formation of non-alcoholic fatty liver, and inhibiting inflammation of subcutaneous adipose tissue.

8. A pharmaceutical combination, characterized in that The invention comprises the allicin oil gel according to any one of claims 1 to 3.

9. The pharmaceutical combination according to claim 8, characterized in that The drug also includes other active ingredients that target fat cells.

10. The pharmaceutical combination according to claim 9, characterized in that The other active ingredients targeting fat cells include one or more of berberine, hypericin, capsaicin, resveratrol and perforin.

Images