Coenzyme Q10 oral soluble film

Abstract

The invention provides a coenzyme Q10 oral soluble film. The coenzyme Q10 oral soluble film comprises the following components in parts by weight: 20-30 parts of coenzyme Q10, a film-forming material and 10-20 parts of a plasticizer, the coenzyme Q10 exists in the form of coenzyme Q10 nano-emulsion, and the film-forming material is water-soluble. When the coenzyme Q10 exists in the form of ultrafine particles or nano microemulsion, the intermiscibility of the coenzyme Q10 with a film-forming material, a plasticizer and other optional auxiliary materials can be remarkably enhanced. The dosages of the components are limited in a specific range, so that the coenzyme Q10 component can be quickly released and absorbed in the application process, and the effect taking speed and bioavailability of the active component are improved. In addition, in the oral soluble film provided by the invention, one part of the active pharmaceutical ingredients can be quickly absorbed by the oral mucosa, and the other part of the active pharmaceutical ingredients enters the gastrointestinal tract along with saliva to be absorbed, so that the effective concentration can be quickly reached; and the dosage form is novel, the medication privacy of a user is relatively good, and the use time and place are not limited.

Description

Technical Field

[0001] The present application relates to the field of pharmaceutical preparations, and in particular to a coenzyme Q10 orally disintegrating film. Background Art

[0002] Coenzyme Q10 is an antioxidant drug that has strong antioxidant properties, helping the body fight free radicals and slowing down the body's aging process. In addition to its antioxidant properties, Coenzyme Q10 also has the following benefits and functions:

[0003] The first is cardioprotection.

[0004] Coenzyme Q10 deficiency is associated with cardiac dysfunction, particularly in patients with heart failure, where Coenzyme Q10 supplementation can significantly improve survival. Specifically, Coenzyme Q10 improves cardiac function, potentially through its role in cellular energy metabolism. Furthermore, Coenzyme Q10 has been shown to prevent atherosclerosis, thereby reducing the risk of sudden cardiac death.

[0005] The second is the promotion of cellular energy metabolism.

[0006] Coenzyme Q10 is a key coenzyme in cellular energy metabolism, and its supplementation can enhance cellular energy production. In clinical practice, Coenzyme Q10 supplementation has been shown to improve vitality, energy, and stamina, and reduce fatigue. Therefore, Coenzyme Q10 is also used as a supplement by athletes to enhance athletic performance.

[0007] The third is the immune regulation effect.

[0008] Coenzyme Q10 has significant antioxidant properties, with an antioxidant capacity approximately 50 times that of vitamin E. This potent antioxidant effect helps reduce oxidative stress, thereby indirectly enhancing the function of the immune system.

[0009] The fourth type is the reduction of drug side effects.

[0010] Coenzyme Q10 can alleviate the side effects of certain medications, particularly statins. Statins work by lowering cholesterol levels, but they can also cause Coenzyme Q10 levels to drop by up to 40%. Therefore, it's often recommended that Coenzyme Q10 supplementation be taken with statins.

[0011] Currently, the primary commercial dosage form of Coenzyme Q10 is tablets. However, because Coenzyme Q10 is a poorly soluble compound, its oral bioavailability is low and its onset of action is slow. Furthermore, tablets require water to be taken, which can be inconvenient for patients and may increase their psychological burden, compromising treatment effectiveness.

[0012] Oral Soluble Film is an oral preparation made by uniformly dispersing the active pharmaceutical ingredient in a film-forming material. This oral dosage form is very important in the pharmaceutical industry. It disintegrates in saliva within a short period of time and releases the active pharmaceutical ingredient, which is then absorbed through the oral mucosa or, after swallowing, through the gastrointestinal tract. It has a rapid onset of action and high bioavailability. It can be administered quickly and accurately at any time and place without the need for water, without delaying medication. Furthermore, many users have difficulty swallowing conventional tablets, so this dosage form provides a safe and reliable route of administration for this population.

[0013] Although orally disintegrating film as a new oral preparation has attracted attention due to its advantages such as rapid disintegration and high bioavailability, the development of orally disintegrating film preparations for coenzyme Q10 has not been seen in academic research or clinical application reports. Summary of the Invention

[0014] In view of the above-mentioned problems existing in the prior art, the present application provides a coenzyme Q10 orally dissolving film, which comprises, by weight, 20 to 30 parts of coenzyme Q10, 30 to 50 parts of film-forming material and 10 to 20 parts of plasticizer, wherein the coenzyme Q10 is a nano-microemulsion and the film-forming material is water-soluble.

[0015] Beneficial effects:

[0016] When coenzyme Q10 exists in the form of ultrafine particles or nano-microemulsions, its compatibility with film-forming materials, plasticizers and other optional excipients can be significantly enhanced. At the same time, limiting the dosage of each of the above components to a specific range can enable the coenzyme Q10 component in the orally dissolving film to be quickly released and absorbed during the application process, thereby improving the onset speed and bioavailability of the active ingredient. In addition, in the orally dissolving film provided by the present application, a portion of the active ingredient of the drug can be quickly absorbed by the oral mucosa, and the other part enters the gastrointestinal tract with saliva for absorption, which can reach the effective concentration faster and improve the efficacy; and the dosage form is novel, the user's medication privacy is better, and the time and place of use are not restricted. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 The figure shows the SEM electron microscope image of the coenzyme Q10 orally disintegrating film prepared in Example 1 at a magnification of 2000.

[0018] Figure 2 The figure shows the SEM electron microscope image of the coenzyme Q10 orally disintegrating film prepared in Example 1 at a magnification of 1000.

[0019] Figure 3 The figure shows the SEM electron microscope image of the coenzyme Q10 orally disintegrating film prepared in Example 1 at a magnification of 500.

[0020] Figure 4 The figure shows a SEM electron microscope image of raw material coenzyme Q10 at a magnification of 2000.

[0021] Figure 5 The figure shows a SEM electron microscope image of raw material coenzyme Q10 at a magnification of 1000.

[0022] Figure 6 The figure shows a SEM electron microscope image of raw material coenzyme Q10 at a magnification of 500.

[0023] Figure 7 A comparison chart of the dissolution curves of the coenzyme Q10 orally dissolving film provided by the present application and the commercially available coenzyme Q10 capsules is shown. DETAILED DESCRIPTION

[0024] In the description of the present application, unless otherwise specified, “above” and “below” include the number.

[0025] Unless otherwise specified, the terms used in this application have the commonly understood meanings commonly understood by those skilled in the art. Unless otherwise specified, the numerical values ​​of the various parameters mentioned in this application can be measured using various measurement methods commonly used in the art (for example, they can be tested according to the methods given in the examples of this application).

[0026] The following will be combined with the accompanying drawings in the embodiments of this application to clearly and completely describe the technical solutions in the embodiments of this application. Obviously, the embodiments described are only part of the embodiments of this application, not all of the embodiments. The following embodiments and features in the embodiments can be combined with each other unless there is a conflict.

[0027] A typical embodiment of the present application provides a coenzyme Q10 orally dissolving film, which comprises, by weight, 20 to 30 parts of coenzyme Q10, 30 to 50 parts of film-forming material, and 10 to 20 parts of plasticizer, wherein the coenzyme Q10 is a nano-microemulsion and the film-forming material is water-soluble.

[0028] When coenzyme Q10 is present in the form of ultrafine particles or nano-microemulsions, its compatibility with film-forming materials, plasticizers and other optional excipients can be significantly enhanced. At the same time, limiting the dosage of each of the above components to a specific range can enable the coenzyme Q10 component in the orally dissolving film to be quickly released and absorbed during the application process, thereby improving the onset speed and bioavailability of the active ingredient. In addition, in the orally dissolving film provided by the present application, a portion of the active ingredient of the drug can be quickly absorbed by the oral mucosa, and the other part enters the gastrointestinal tract with saliva for absorption, which can reach the effective concentration faster and improve the efficacy; and the dosage form is novel, the user's medication privacy is better, and the time and place of use are not restricted.

[0029] In some embodiments of the present application, the coenzyme Q10 oral-dissolving film comprises the following parts by weight of coenzyme Q10: 20 parts, 21 parts, 22 parts, 23 parts, 24 parts, 25 parts, 26 parts, 27 parts, 28 parts, 29 parts, 30 parts, or a range formed by any of the above values; the coenzyme Q10 oral-dissolving film comprises the following parts by weight of film-forming material: 30 parts, 32 parts, 34 parts, 36 parts, 38 parts, 40 parts, 42 parts, 44 parts, 46 parts, 48 ​​parts, 50 parts, or a range formed by any of the above values; the coenzyme Q10 oral-dissolving film comprises the following parts by weight of plasticizer: 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts, 18 parts, 19 parts, 20 parts, or a range formed by any of the above values.

[0030] In some embodiments of the present application, during the preparation of the coenzyme Q10 orally dissolving film, coenzyme Q10 forms an enzyme Q10 nanoemulsion comprising coenzyme Q10, a surfactant, and a solubilizing agent. Preferably, the weight ratio of coenzyme Q10, surfactant, and solubilizing agent is 10:(0.5-5.0):(2.0-10.0). Illustratively, the weight ratio of Coenzyme Q10, surfactant, and solubilizer is 10:0.5:2.0, 10:0.5:3.0, 10:0.5:4.0, 10:0.5:5.0, 10:0.5:6.0, 10:0.5:7.0, 10:0.5:8.0, 10:0.5:9.0, 10:0.5:10.0, 10:1.5:2.0, 10:1.5:3.0, 10:1.5:4.0, 10:1.5:5.0, 10:1.5:6.0, 10:1.5:7.0, 10:1.5:8.0, 10:1.5:9.0, 10:1.5:10.0 , 10:2.0:2.0, 10:2.0:3.0, 10:2.0:4.0, 10:2.0:5.0, 10:2.0:6.0, 10:2.0:7.0, 10:2.0:8.0, 10:2.0:9.0, 10:2.0:10.0, 10:2.5:2.0, 10:2.5:3.0, 10:2.5:4.0, 10:2.5:5.0, 10:2.5:5.5, 10:2.5:6.0, 10:2.5:7.0, 10:2.5:8.0, 10:2.5:9.0, 10:2.5:10.0 or a range formed by any of the above values.

[0031] In some embodiments of the present application, the solvent is a glycerol aqueous solution; the surfactant includes but is not limited to one or more of sodium lauryl sulfate, sodium tetradecyl sulfate, Tween 20, lecithin, Tween 80 and Span.

[0032] In some embodiments of the present application, the film-forming material includes, but is not limited to, one or more of polyethylene oxide, cellulose derivatives, polyvinyl pyrrolidone, polyvinyl alcohol (PVA), xanthan gum, carrageenan, gum arabic, and sodium alginate. Preferably, the cellulose derivative is selected from one or more of hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, and carboxymethyl cellulose.

[0033] In some embodiments of the present application, the cellulose derivative is hydroxypropyl methylcellulose, and at 20°C, when the mass volume ratio of hydroxypropyl methylcellulose to water is 2% (w / v), the viscosity of the hydroxypropyl methylcellulose aqueous solution formed is less than 50 mPa·s. Compared with other cellulose derivatives, hydroxypropyl methylcellulose with the above viscosity range is beneficial for improving the rapid dissolution rate of the coenzyme Q10 orodissolving film in the oral cavity. In order to further improve its dissolution performance in the oral cavity, preferably, at 20°C, when the mass volume ratio of hydroxypropyl methylcellulose to water is 2% (w / v), the viscosity of the hydroxypropyl methylcellulose aqueous solution formed is a solution of 3 to 20 mPa·s.

[0034] The mass-volume concentration is calculated as the mass of the solute divided by the volume of the solvent. For example, if hydroxypropyl methylcellulose is 2 g and the volume of water is 100 mL, then the mass-volume concentration of the hydroxypropyl methylcellulose aqueous solution is 2% (w / v).

[0035] In some embodiments of the present application, the plasticizer includes, but is not limited to, one or more of propylene glycol, dibutyl phthalate, triethyl citrate, triacetin, and polyethylene glycol.

[0036] In some embodiments of the present application, the orally disintegrating Coenzyme Q10 film further comprises 2 to 10 parts by weight of a filler. Preferably, the filler includes, but is not limited to, one or more of microcrystalline cellulose, low-substituted hydroxypropyl cellulose, pregelatinized starch, and cross-linked sodium carboxymethyl cellulose. Alternatively, the orally disintegrating Coenzyme Q10 film further comprises the following filler amounts by weight: 2 parts, 3 parts, 4 parts, 5 parts, 6 parts, 7 parts, 8 parts, 9 parts, 10 parts, or any range thereof.

[0037] In some embodiments of the present application, the Coenzyme Q10 orally disintegrating film further comprises 2 to 4 parts by weight of a flavoring agent; preferably, the flavoring agent comprises a sweetener and / or a fragrance. Optionally, the Coenzyme Q10 orally disintegrating film further comprises 2.0 parts, 2.5 parts, 3.0 parts, 3.5 parts, 4.0 parts, or any range thereof.

[0038] Preferably, the flavoring agents include but are not limited to one or more of sucralose, xylitol, glucose, fructose, acesulfame potassium, aspartame, glycyrrhizin, stevioside, sucralose, sorbitol, mannitol, xylitol and erythritol; the flavoring agents include but are not limited to one or more of peppermint oil, menthol, mint essence, sweet orange essence, mixed berry essence and apple, pear, peach, grape, strawberry, cherry, pineapple, apricot and other fruit flavors.

[0039] In some embodiments of the present application, the orally dissolving Coenzyme Q10 film further comprises 2 to 4 parts by weight of a transdermal absorption enhancer. Optionally, the transdermal absorption enhancer includes, but is not limited to, one or more of laurocapram, dimethyl sulfoxide, oleic acid, cyclodextrin, menthol, and peppermint oil. Laurocapram is a non-polar transdermal enhancer that promotes transdermal penetration of both lipophilic and hydrophilic drugs. It has low toxicity, with an oral LD50 of >7g / kg. It is mildly irritating to the skin and can soften keratin, enhancing permeability and allowing drugs to penetrate the skin barrier, increasing local or systemic blood drug concentrations, improving the bioavailability of the formulation, and enhancing the rate of drug absorption. Cyclodextrin forms an inclusion complex with Coenzyme Q10, increasing the solubility and stability of Coenzyme Q10 in an aqueous matrix and promoting its distribution and diffusion across the mucosa. Cyclodextrins include α-cyclodextrin, β-cyclodextrin, and hydroxypropyl-β-cyclodextrin. Therefore, to further improve the bioavailability and drug absorption rate of the orally disintegrating Coenzyme Q10 film, the transdermal absorption enhancer preferably includes laurocapram and / or cyclodextrin. Optionally, the orally disintegrating Coenzyme Q10 film includes the following parts by weight of the transdermal absorption enhancer: 2.0 parts, 2.5 parts, 3.0 parts, 3.5 parts, 4.0 parts, or any range formed by the above values.

[0040] In some embodiments of the present application, the Coenzyme Q10 orally disintegrating film further comprises 0-0.1 parts by weight of a colorant. The use of a colorant is intended to adjust the appearance and color of the Coenzyme Q10 orally disintegrating film according to specific needs to enhance the user's visual experience and overall satisfaction. Optionally, the colorant includes, but is not limited to, lakes, pigments, and FD&C dyes (colorants regulated by the U.S. Food and Drug Administration (FDA) for use in food, drugs, and cosmetics).

[0041] In some embodiments of the present application, the tensile strength of the coenzyme Q10 orally disintegrating film in a size of 1.3 cm×6 cm is greater than 10 N, and the coenzyme Q10 orally disintegrating film can be completely dispersed and dissolved in water at 37±2° C. within 60 seconds.

[0042] The second aspect of the present application further provides a method for preparing a coenzyme Q10 orally disintegrating film, comprising:

[0043] (1) Coenzyme Q10 is melted and mixed with a solubilizer and an optional surfactant, and then subjected to high-speed shearing to obtain a coenzyme Q10 crude oil-water solution.

[0044] (2) The crude coenzyme Q10 oil-water solution is homogenized under high pressure to obtain a coenzyme Q10 nanoemulsion.

[0045] (3) The above-mentioned coenzyme Q10 nano-microemulsion and other raw materials in the orally disintegrating film formula are mixed and degassed to obtain a preliminary glue solution.

[0046] (4) The prepared glue solution is coated, dried and cut to obtain the desired coenzyme Q10 orally disintegrating film.

[0047] In some embodiments of the present application, in step (1), coenzyme Q10 is melted at 40-60°C.

[0048] In some embodiments of the present application, the temperature of the high-speed shear process is 40-60° C., the rotation speed is 3000-8000 r / min, and the stirring time is 1-5 min.

[0049] In some embodiments of the present application, the solubilizer used in step (1) includes 1 wt% to 5 wt% of a surfactant and 20 wt% to 60 wt% (optionally 43.5 wt%) of a glycerol aqueous solution, wherein the weight ratio of glycerol to water in the solubilizer is 1:4.

[0050] In some embodiments of the present application, in step (2), the pressure of the high-pressure homogenization process is 500-1500 MPa, and the number of homogenizations is 3-6 times. Exemplarily, the pressure of the high-pressure homogenization process is 500MPa, 550MPa, 600MPa, 650MPa, 700MPa, 750MPa, 800MPa, 850MPa, 900MPa, 950MPa, 1000MPa, 1050MPa, 1100MPa, 1150MPa, 1200MPa, 1250MPa, 1300MPa, 1350MPa, 1400MPa, 1450MPa, 1500MPa or the range formed by any two of the above values. In order to make the raw materials mixed evenly and further improve the tensile strength and dissolution rate of the orally dissolving film, preferably, the pressure of the high-pressure homogenization process is 800-1500MPa.

[0051] In some embodiments of the present application, in step (3), the temperature of the drying process is 20-90°C, preferably 50-60°C.

[0052] The present application is further described in detail below with reference to specific embodiments. These embodiments should not be construed as limiting the scope of protection claimed in this application.

[0053] Performance testing method:

[0054] (1) Determination of dissolution

[0055] The hanging basket is suspended on a metal bracket through the stainless steel shaft at the upper end and immersed in a 1000mL beaker. The position of the hanging basket is adjusted so that the screen is 25mm away from the bottom of the beaker when it descends. The beaker is filled with artificial saliva at a temperature of 37±1℃. The liquid level is adjusted so that the screen is 15mm below the liquid level when the hanging basket rises. 2 The membranes of the Examples or Comparative Examples (each containing 2±0.2 mg of nicotine) were placed in the glass tubes of the aforementioned hanging baskets, baffled, and the disintegration instrument was activated for testing. The disintegration time was recorded. Simultaneously, 2 mL of artificial saliva samples were taken at 30 seconds, 1 minute, 3 minutes, 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, and 2 hours. The samples were then assayed for Q10 content using an HPLC external standard method, and the cumulative Q10 release (%) was calculated. After each sampling, the volume of artificial saliva removed (2 mL) was replenished with fresh artificial saliva. For Q10 content assay methods, refer to GB / T 22252-2008.

[0056] (2) Tensile properties test

[0057] Orally disintegrating films should possess excellent physical properties to meet the requirements of production, transportation, storage, and clinical use. Tensile strength is the ultimate strength of a material under a tensile load. A high tensile strength indicates high film strength. The tensile properties of the product were measured using an intelligent electronic tensile testing machine (XLW, Jinan Languang Electromechanical Technology Co., Ltd.) with settings of 60 mm in length, 13 mm in width, 60 μm in thickness, and a speed of 100 mm / min.

[0058] The preparation method of the coenzyme Q10 orally dissolving film in the embodiment is as follows:

[0059] Coenzyme Q10 powder is added to a surfactant and glycerol aqueous solution, heated to 60°C under nitrogen protection until the coenzyme Q10 melts. The mixture is then stirred at 40-60°C using a high-speed shear mixer at 3,000-8,000 rpm for 10-15 minutes to form a crude oil-water emulsion. The resulting aqueous emulsion is then passed through a homogenizer three times under homogenizing pressure, with the temperature controlled to not exceed 60°C during the homogenization cycle, to produce a coenzyme Q10 microemulsion. The resulting microemulsion, transdermal absorption enhancer, and other excipients are then added to water and thoroughly stirred at 60°C. The membrane material is then added and stirred until uniform, and the mixture is degassed and defoamed to produce a uniform, high-viscosity adhesive. The adhesive is then coated, film-formed, dried at 50-60°C, and slit to produce the desired coenzyme Q10 orally dissolving film.

[0060] Example 1

[0061] Products 1 to 5 are used to investigate the effect of raw material homogenization on product performance, and the specific formulas are shown in Table 1.

[0062] Table 1

[0063]

[0064]

[0065] Note: The water in the formulation is removed in the final product and therefore does not need to be presented in the above table.

[0066] The film prepared from the above components was dark yellow in color, exhibited good flatness, foldability, plasticity, and toughness, and had a tensile strength between 10 and 16 N, meeting the requirements for cutting, packaging, transportation, and clinical use. Dissolution data are shown in Table 2.

[0067] Table 2

[0068]

[0069] The above results show that the homogenization and emulsification of coenzyme Q10 raw materials have a significant effect on product dissolution. When the homogenization pressure is 500 MPa or above, the dissolution rate of the orally dissolving film product can reach more than 97% within 30 minutes.

[0070] The SEM electron microscope images of the coenzyme Q10 orally soluble film prepared in Example 1 at magnifications of 2000, 1000 and 500 are shown in FIG. Figures 1 to 3 .

[0071] The SEM electron microscope images of the raw material coenzyme Q10 used in the embodiment at magnifications of 2000, 1000 and 500 are shown in FIG. Figures 4 to 6 .

[0072] Example 2

[0073] Products 6 to 8 are used to illustrate the effects of the dosage of API, film-forming material, and plasticizer on product quality, and their specific formulas are shown in Table 3.

[0074] Table 3

[0075]

[0076] Note: The water in the formulation is removed in the final product and therefore does not need to be presented in the above table.

[0077] Orally disintegrating films prepared from the above components exhibit good flatness. However, as the plasticizer ratio decreases, the film's softness and toughness decrease, making the film more brittle and prone to breakage, which can hinder film slitting and packaging. Furthermore, the above results indicate that when the Coenzyme Q10 ratio is within the range of 20-30 wt%, the film-forming material ratio is within the range of 20-50 wt%, and the plasticizer ratio is within the range of 10-20 wt%, the product exhibits excellent plasticity, toughness, and dissolution properties.

[0078] Example 3

[0079] Products 9 to 11 are used to illustrate the effects of solubilizers and transdermal absorption enhancers on product quality, and their specific formulas are shown in Table 4.

[0080] Table 4

[0081]

[0082] Note: The water in the formula is removed in the final product and therefore does not need to be presented in the above table; the homogenization conditions are the same as in Examples 6 to 8.

[0083] The films prepared from these components exhibited excellent flatness, foldability, plasticity, and toughness, with a tensile strength of 13 to 17 N, meeting the requirements for cutting, packaging, transportation, and clinical use. These results indicate that when the filler ratio is within the range of 2 to 10 wt% and the transdermal absorption enhancer ratio is within the range of 0.5 to 5 wt%, the product's physical properties meet the requirements. However, at a ratio of 2 to 4 wt%, the stickiness is less pronounced and the mouthfeel is better.

[0084] Example 4

[0085] The dissolution rates of the coenzyme Q10 orally dissolving film (Product 9) prepared in this application and the Qunol UltraCoQ10 Dietary Supplement Softgels (90 capsules, manufactured in the United States) were measured. The determination method was an Agilent 1260 high performance liquid chromatograph, with a mobile phase of methanol:anhydrous ethanol = 1:1, a wavelength of 275 nm, and a DAD detector. The comparative results are shown in Figure 7 .

[0086] Product 9 has the least amount of transdermal absorbent and can be considered as a less effective formulation. Figure 7 It can be seen that compared with commercially available capsule preparations, the coenzyme Q10 orally dissolving film (Product 9) prepared in this application can release more rapidly. This shows that when the amount of API is further reduced or the solubilizer is increased, the coenzyme Q10 orally dissolving film prepared with other formulations also has the advantage of faster release compared to tablets.

[0087] Example 5

[0088] Used to illustrate the absorption performance of the coenzyme Q10 orally disintegrating film prepared in this application in the oral cavity.

[0089] Products 8 to 11 were placed in the mouth and timing was started. After 15 minutes of ingestion, the products were spit out. Meanwhile, blood samples were collected at 0, 10, 20, 30, and 60 minutes, and the Coenzyme Q10 concentrations were measured using liquid chromatography. The results are shown in Table 5.

[0090] Table 5

[0091]

[0092] The results in the table above show that the addition of a transdermal absorption enhancer facilitates rapid absorption of the active ingredient in the oral cavity, and the absorption effect is even better when the dosage is limited to 2-4 wt%. Based on this, it can be inferred that this effect also occurs in the gastrointestinal tract, helping the drug to take effect more quickly.

[0093] Example 6

[0094] In order to investigate the effects of different transdermal absorption enhancers on the absorption of coenzyme Q10, the effects of different transdermal absorption enhancers on the absorption of coenzyme Q10 were compared. The specific compositions are shown in Table 6.

[0095] Table 6

[0096]

[0097] Note: The water in the formulation is removed in the final product and therefore does not need to be presented in the above table.

[0098] Products 3, 8, 12, 13, 14, and 15 were placed in the mouth and timed. After 15 minutes of ingestion, the products were spit out. Meanwhile, blood samples were collected at 0, 10, 20, 30, and 60 minutes, and the Coenzyme Q10 concentrations were measured using liquid chromatography. The results are shown in Table 7.

[0099] Table 7

[0100]

[0101]

[0102] The results in the table above indicate that the addition of a transdermal absorption enhancer facilitates rapid absorption of the active ingredient in the oral cavity. This suggests that a similar effect also exists in the gastrointestinal tract, contributing to a more rapid onset of drug effectiveness. Comparing several transdermal absorption enhancers, under the same conditions, lauroyl azone demonstrates superior absorption-enhancing effects.

[0103] Example 6

[0104] To investigate how the properties, characteristics, and content of Coenzyme Q10 orally disintegrating film change over time under the influence of environmental factors (such as temperature and humidity), the product's storage conditions and shelf life were determined based on stability study data. During the long-term stability testing, product 1 through 3 were stored at 25°C and 60% ± 5% RH for 24 months.

[0105] The long-term stability test results of Product 1 are shown in Table 8.

[0106] Table 8

[0107]

[0108]

[0109] The results of the long-term stability test of Product 2 are shown in Table 9.

[0110] Table 9

[0111]

[0112] The results of the long-term stability test of Product 3 are shown in Table 10.

[0113] Table 10

[0114]

[0115] The above results show that the three types of coenzyme Q10 orally disintegrating films did not change in properties under the conditions of 25°C / 60±5% RH (0 to 24 months), and the content was within the qualified range. There were no significant changes in other test items, and the test results all met the orally disintegrating film stability quality standards. This proves that the coenzyme Q10 orally disintegrating film provided by this application is stable in quality at room temperature, safe and reliable, with a shelf life of at least 24 months, which meets the clinical requirements.

[0116] Although some exemplary embodiments of the present application have been illustrated and described, the present application is not limited to the disclosed embodiments. On the contrary, those skilled in the art will recognize that some modifications and changes may be made to the described embodiments without departing from the spirit and scope of the present application as described in the appended claims.

Claims

1. A coenzyme Q10 orally disintegrating film, characterized in that: The coenzyme Q10 orally dissolving film comprises 20 to 30 parts of coenzyme Q10, 30 to 50 parts of film-forming material and 10 to 20 parts of plasticizer by weight, wherein the coenzyme Q10 is a nano-microemulsion and the film-forming material is water-soluble.

2. The coenzyme Q10 orally disintegrating film according to claim 1, characterized in that During the preparation of the coenzyme Q10 orally dissolving film, the coenzyme Q10 forms a coenzyme Q10 nano-microemulsion, which includes the coenzyme Q10, a surfactant, and a solubilizer.

3. The coenzyme Q10 orally disintegrating film according to claim 2, characterized in that In parts by weight, the weight ratio of the coenzyme Q10, the surfactant and the solubilizer is 10:(0.5-5.0):(2.0-10.0).

4. The coenzyme Q10 orally disintegrating film according to claim 2 or 3, characterized in that The solubilizer is a glycerol aqueous solution; the surfactant includes one or more of sodium lauryl sulfate, sodium tetradecyl sulfate, Tween 20, lecithin, Tween 80 and Span.

5. The coenzyme Q10 orally disintegrating film according to any one of claims 1 to 4, characterized in that The film-forming material comprises one or more of polyethylene oxide, cellulose derivatives, polyvinyl pyrrolidone, polyvinyl alcohol, xanthan gum, carrageenan, gum arabic and sodium alginate; Preferably, the cellulose derivative includes one or more of hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose and carboxymethyl cellulose.

6. The coenzyme Q10 orally disintegrating film according to claim 5, characterized in that The cellulose derivative is hydroxypropyl methylcellulose, and at 20° C., when the mass volume ratio of the hydroxypropyl methylcellulose to water is 2% (w / v), the viscosity of the formed hydroxypropyl methylcellulose aqueous solution is less than 50 mPa·s; Preferably, at 20° C., when the mass volume ratio of the hydroxypropyl methylcellulose to water is 2% (w / v), the viscosity of the formed hydroxypropyl methylcellulose aqueous solution is 3 to 20 mPa·s.

7. The coenzyme Q10 orally disintegrating film according to claim 1, characterized in that The plasticizer includes one or more of propylene glycol, dibutyl phthalate, triethyl citrate, triacetin and polyethylene glycol.

8. The coenzyme Q10 orally disintegrating film according to any one of claims 1 to 7, characterized in that: The coenzyme Q10 orally disintegrating film also meets any one or more of the following conditions: (1) The coenzyme Q10 orally disintegrating film further comprises 2 to 10 parts of a filler by weight; (2) The coenzyme Q10 orally disintegrating film further comprises 2 to 4 parts of a flavoring agent by weight; (3) The coenzyme Q10 orally dissolving film further comprises 2 to 4 parts by weight of a transdermal absorption enhancer; (4) The coenzyme Q10 orally disintegrating film further comprises 0 to 0.1 parts of a colorant by weight.

9. The coenzyme Q10 orally disintegrating film according to claim 8, characterized in that When the coenzyme Q10 orally disintegrating film satisfies at least condition (1), the filler comprises one or more of microcrystalline cellulose, low-substituted hydroxypropyl cellulose, pregelatinized starch, and cross-linked sodium carboxymethyl cellulose; When the coenzyme Q10 orally disintegrating film satisfies at least condition (2), the flavoring agent includes a sweetener and / or a flavoring agent; When the coenzyme Q10 orally dissolving film satisfies at least condition (3), the transdermal absorption enhancer comprises one or more of laurocapram, dimethyl sulfoxide, oleic acid, cyclodextrin, menthol and peppermint oil.

10. The coenzyme Q10 orally disintegrating film according to any one of claims 1 to 9, characterized in that: The coenzyme Q10 orally disintegrating film has a breaking force greater than 10N in a size of 1.3cm×6cm and can be completely dispersed and dissolved in water at 37±2°C within 60s.

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