A fast film-forming nystatin oral gel spray and its preparation method

Abstract

The present invention relates to a fast film-forming nystatin oral gel spray and a preparation method thereof, belonging to the field of biomedical technology, and solves the problem that the nystatin dosage form in the prior art is not suitable for children, especially newborns and infants. The fast film-forming nystatin oral gel spray includes nystatin, xanthan gum, polyethylene glycol-polyvinyl alcohol graft copolymer, glycerol and a solvent, and the solvent is water. The fast film-forming nystatin oral gel spray of the present invention is more suitable for use by children, especially newborns and infants.

Description

Technical Field

[0001] The present invention relates to the field of biomedical technologies, and particularly to a fast film-forming nystatin oral gel spray and a preparation method thereof. Background Art

[0002] Oral candidiasis, also known as thrush, snow mouth disease, and candidiasis albicans, is an oral mucosal disease caused by Candida albicans infection, manifested as the formation of white plaque on the surface of oral mucosa such as the tongue, cheek, palate, gingiva or inner lip. It is a common oral disease in children, mostly occurring in neonates and infants, with an incidence rate of about 4%. Seriously, patients such as neonates and infants will have restlessness, crying, difficulty in breastfeeding, etc. due to pain, which affects the physical and mental health of children and causes serious troubles to the parents of children. If not treated in time, the infection range will continue to expand, involving parts such as the throat, tonsils, and gingiva, spreading to tissues such as the bronchus and lungs, causing complications such as esophagitis and pulmonary candidiasis, and even secondary to serious consequences such as septicemia. Candida exists in the oral cavity of about 60% of healthy people. In recent years, due to the abuse of antibiotics and other reasons leading to dysbacteriosis and decreased immunity of patients, the incidence rate of oral candidiasis has been increasing day by day.

[0003] Nystatin is the most commonly used drug for the treatment of thrush in clinics and has been included in the Expert Consensus on the Diagnosis and Treatment of Candidiasis (2020 Edition). Nystatin belongs to polyene antifungal drugs, which can selectively bind to ergosterol on the fungal cell membrane, causing changes in membrane permeability, so that the contents such as electrolytes and / or small molecule substances in the fungal cells leak out to play an antifungal role. At present, the dosage forms of nystatin include tablets, suppositories, effervescent tablets, etc. There is no preparation for children. Clinically, nystatin tablets are mostly ground into powder and diluted into a solution or suspension and applied in the oral cavity of children. It is inconvenient to use, has a high dosing frequency, poor medication compliance, poor taste, is easy to cause adverse reactions such as nausea, and the membrane permeability of nystatin is low, and it is difficult to be fully dissolved and absorbed into the systemic circulation to exert its drug effect after administration. Summary of the Invention

[0004] In view of the above analysis, the embodiments of the present invention aim to provide a fast film-forming nystatin oral gel spray and a preparation method thereof to solve the problem that the existing dosage forms of nystatin are not suitable for children, especially neonates and infants.

[0005] On the one hand, the embodiments of the present invention provide a fast film-forming nystatin oral gel spray, which includes nystatin, xanthan gum, polyethylene glycol-polyvinyl alcohol graft copolymer, glycerol and a solvent, and the solvent is water.

[0006] Preferably, the molecular weight of the polyethylene glycol-polyvinyl alcohol graft copolymer is 40,000 - 50,000 daltons.

[0007] Preferably, based on the total mass of the fast film-forming nystatin oral gel spray, the mass content of the polyethylene glycol-polyvinyl alcohol graft copolymer is 0.1-8%.

[0008] Preferably, the relative molecular weight of the xanthan gum is 1×10 6 ~3×10 6 .

[0009] Preferably, based on the total mass of the fast film-forming nystatin oral gel spray, the mass content of the xanthan gum is 0.04-4%.

[0010] Preferably, the drug loading amount of the nystatin is greater than 0.5%.

[0011] Preferably, the mass ratio of the xanthan gum, polyethylene glycol-polyvinyl alcohol graft copolymer, glycerol and nystatin is (0.01-5):(0.025-10):(1.25-25):1.

[0012] Preferably, the fast film-forming nystatin oral gel spray further comprises a solubilizer, and the solubilizer is Tween 80 and / or lecithin;

[0013] And / or, the fast film-forming nystatin oral gel spray further comprises a flavoring agent and a preservative.

[0014] Preferably, the pH of the fast film-forming nystatin oral gel spray is 5.4-6.5;

[0015] And / or, the gel viscosity of the fast film-forming nystatin oral gel spray is 0.1-16 Pas.

[0016] On the other hand, the present invention also provides a preparation method of a fast film-forming nystatin oral gel spray for preparing the above-mentioned fast film-forming nystatin oral gel spray, and the preparation method comprises:

[0017] Mix the polyethylene glycol-polyvinyl alcohol graft copolymer, xanthan gum with a part of the solvent to obtain solution A;

[0018] Mix glycerol, nystatin with the remaining solvent to obtain solution B;

[0019] Mix solution A and solution B to obtain the fast film-forming nystatin oral gel spray.

[0020] Compared with the prior art, the present invention can at least achieve one of the following beneficial effects:

[0021] 1. The fast film-forming nystatin oral gel spray of the present invention synergistically regulates the rheological properties of the gel through xanthan gum, polyethylene glycol-polyvinyl alcohol graft copolymer and glycerol, which not only retains the low-viscosity gel for sprayable form, but also can be sprayed to form a film quickly and disperse at the oral lesion site, is not easy to fall off, and can achieve long-term adhesion. The gel system is formulated with nystatin, making the nystatin oral gel spray have excellent spray film-forming property, drug dispersibility and drug sustained-release effect, etc., which can improve the convenience of drug use, prolong the action time of the drug in the oral cavity, reduce the number of drug administrations, improve patient compliance and treatment effect, and the solvent is water, making it more suitable for use in children, especially newborns and infants.

[0022] 2. The fast film-forming nystatin oral gel spray of the present invention can achieve a pH close to neutral without adding acid-base components, for example, the pH is 5.4 - 6.5; the film-forming time can be as short as within 12 min; the film rupture time can reach more than 23 min; the gel viscosity is 0.1 - 16 Pas, further preferably 0.1 - 10 Pas, and can be smoothly sprayed without resistance; the drug release amount within 48 h can reach more than 45%.

[0023] 3. The fast film-forming nystatin oral gel spray of the present invention also contains a flavoring agent suitable for children, and the gel spray is optimized for taste masking and flavor correction through the flavoring agent to improve the taste of drug use.

[0024] 4. The present invention uses the homogenization method to prepare the fast film-forming nystatin oral gel spray, and it is not easy to occur stratification and sedimentation when placed at normal temperature or low temperature.

[0025] In the present invention, the above technical solutions can also be combined with each other to achieve more preferred combination solutions. Other features and advantages of the present invention will be described in the subsequent specification, and some advantages can be made obvious from the specification, or understood by implementing the present invention. The objectives and other advantages of the present invention can be realized and obtained from the content specifically pointed out in the specification and the drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] The drawings are only for the purpose of showing specific embodiments, and are not considered as a limitation to the present invention. Throughout the drawings, the same reference numerals represent the same components.

[0027] Figure 1 It is the drug release curve of the fast film-forming nystatin oral gel spray of Example 1.

[0028] Figure 2 It is the appearance state of drug dispersion after preparation of Examples 1, 6 and Comparative Examples 2, 3, 4.

[0029] Figure 3Appearance states of the stability of Examples 1 and 6 and Comparative Examples 2, 3, and 4 after standing at room temperature for 24 h. Detailed implementation manners

[0030] The following will specifically describe the preferred embodiments of the present invention with reference to the accompanying drawings. The accompanying drawings form a part of this application and are used together with the embodiments of the present invention to explain the principles of the present invention, and are not used to limit the scope of the present invention.

[0031] In the prior art, nystatin tablets are ground into powder and diluted into a solution or suspension for application in the oral cavity of children to treat oral thrush in children. However, this method is not suitable for children because, for children, especially newborns and infants, after the drug is applied in their oral cavity, the drug is likely to fall off, thus increasing the frequency of drug administration. Therefore, the inventors of the present invention have developed a gel spray that can quickly form a film in the oral cavity after being formulated with nystatin, and has good film adhesion, drug dispersion, and drug sustained-release properties.

[0032] Based on this, the present invention provides a fast film-forming nystatin oral gel spray, which includes nystatin, xanthan gum, polyethylene glycol-polyvinyl alcohol graft copolymer, glycerol, and a solvent, and the solvent is water.

[0033] It should be noted that the fast film-forming nystatin oral gel spray of the present invention is realized by being loaded in a spray device for spraying.

[0034] Compared with the prior art, the fast film-forming nystatin oral gel spray of the present invention synergistically adjusts the rheological properties of the gel through xanthan gum, polyethylene glycol-polyvinyl alcohol graft copolymer, and glycerol. It not only retains the morphology of a low-viscosity gel (preferably with a viscosity of 0.1 - 16 Pas) that can be sprayed, but also can quickly form a film by spraying and disperse at the oral lesion site, is not easy to fall off, and can achieve long-term adhesion. This gel system is formulated with nystatin, making the nystatin oral gel spray have excellent spray film-forming property, drug dispersion property, and drug sustained-release effect, which can improve the convenience of medication, extend the action time of the drug in the oral cavity, reduce the number of drug administrations, improve patient compliance and treatment effect, and the solvent is water, making it more suitable for use in children, especially newborns and infants.

[0035] In the present invention, the xanthan gum, polyethylene glycol-polyvinyl alcohol graft copolymer, and glycerol synergistically adjust the rheological properties of the gel. Among them, in addition to synergistically adjusting the rheological properties of the gel with glycerol and xanthan gum, the polyethylene glycol-polyvinyl alcohol graft copolymer also has the effect of promoting the formation of a film by gel spraying.

[0036] Exemplarily, the polyethylene glycol-polyvinyl alcohol graft copolymer is composed of polyvinyl alcohol units and polyethylene glycol units, wherein the content of polyvinyl alcohol units is 70% to 80%, and the content of polyethylene glycol units is 20% to 30%.

[0037] Exemplarily, the molecular weight of the polyethylene glycol-polyvinyl alcohol graft copolymer is 40,000 to 50,000 Daltons. If the molecular weight of the polyethylene glycol-polyvinyl alcohol graft copolymer is too large, it will lead to an increase in gel viscosity and a change in rheological properties; if the molecular weight of the polyethylene glycol-polyvinyl alcohol graft copolymer is too small, it will reduce the gel viscosity.

[0038] Exemplarily, based on the total mass of the fast film-forming nystatin oral gel spray, the mass content of the polyethylene glycol-polyvinyl alcohol graft copolymer is 0.1% to 8%, such as 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%. Preferably it is 0.25% to 7.5%, more preferably 0.4% to 7%, and even more preferably 0.5 - 6%. If the mass content of the polyethylene glycol-polyvinyl alcohol graft copolymer is too high, the gel viscosity will increase, and it may increase the potential safety risk of children's medication; if the mass content of the ethylene glycol-polyvinyl alcohol graft copolymer is too low, it will prolong the film-forming time of the gel spray.

[0039] Exemplarily, the relative molecular weight of the xanthan gum is 1×10 6 ~3×10 6 . If the relative molecular weight of the xanthan gum is too large, it will lead to too high gel viscosity, change rheological properties, and affect the spraying effect; if the relative molecular weight of the xanthan gum is too small, it will reduce the gel viscosity and affect the residence time of the drug at the lesion site.

[0040] Exemplarily, based on the total mass of the fast film-forming nystatin oral gel spray, the mass content of the xanthan gum is 0.04% to 4%, for example, 0.06%, 0.1%, 0.2%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%. Preferably it is 0.06% to 3%, more preferably 0.1% to 2.5%, and even more preferably 0.2% to 2%. If the mass content of the xanthan gum is too much, it will lead to an increase in gel viscosity, change rheological properties, and the gel is not easy to spray out; if the mass content of the xanthan gum is too little, it will enhance the fluidity of the gel, reduce the adhesiveness, and it is not easy to stay at the lesion site for a long time.

[0041] Exemplarily, based on the total mass of the fast film-forming nystatin oral gel spray, the mass content of glycerol is 5-20%, such as 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%. If the mass content of glycerol is too high, it will increase the gel viscosity, change the rheological properties, and the gel is not easy to spray out; if the mass content of glycerol is too low, it will reduce the drug dispersibility, change the gel rheological properties, make the film body lack toughness, be easy to dry, and be easy to break.

[0042] Exemplarily, the drug loading of nystatin is greater than 0.5%, preferably 0.5-4.5%, more preferably 0.6-4.25%, more preferably 0.8-4%, such as 1%, 1.5%, 2%, 2.5%, 3%, 3.5%. If the drug loading is too large, it will lead to a decrease in the dispersibility of the drug in the gel matrix and it is difficult to accurately quantify the drug administration; if the drug loading is too small, it will increase the dosing frequency and reduce the patient compliance.

[0043] It should be noted that the drug loading refers to the mass content of nystatin based on the total mass of the fast film-forming nystatin oral gel spray.

[0044] Exemplarily, the mass ratio of xanthan gum, polyethylene glycol-polyvinyl alcohol graft copolymer, glycerol and nystatin is (0.01-5):(0.025-10):(1.25-25):1, and further preferably (0.05-2.5):(0.125-7.5):(2-20):1.

[0045] Exemplarily, the fast film-forming nystatin oral gel spray further comprises a solubilizer, and the solubilizer is Tween 80 and / or lecithin. The role of the solubilizer is to increase the drug solubility and make the drug disperse more uniformly in the gel spray.

[0046] Exemplarily, based on the total mass of the fast film-forming nystatin oral gel spray, the mass content of the solubilizer is 0.2-4%. If the content of the solubilizer is too high, it will increase the potential safety risk of the gel spray; if the content of the solubilizer is too low, it will affect the solubility and dispersity of nystatin in the gel spray.

[0047] Exemplarily, the fast film-forming nystatin oral gel spray further comprises a flavoring agent. The gel spray is optimized for taste masking and flavor correction through the flavoring agent to improve the medication taste.

[0048] Exemplarily, the flavoring agent is at least one of sucrose, sucralose and stevioside. The flavoring agent of the present invention is more suitable for children and has higher safety.

[0049] Exemplarily, based on the total mass of the fast film-forming nystatin oral gel spray, the mass content of the flavoring agent is 0.2 to 21%, for example, 1%, 3%, 5%, 7%, 9%, 11%, 13%, 15%, 17%, 19%.

[0050] Exemplarily, the fast film-forming nystatin oral gel spray further comprises a preservative.

[0051] Exemplarily, the preservative is sodium benzoate.

[0052] Exemplarily, based on the total mass of the fast film-forming nystatin oral gel spray, the mass content of the preservative is 0.02 to 2%.

[0053] The fast film-forming nystatin oral gel spray of the present invention can achieve a pH close to neutral without adding acid and base components. Exemplarily, the pH of the fast film-forming nystatin oral gel spray is 5.4 - 6.5.

[0054] Exemplarily, the gel viscosity of the fast film-forming nystatin oral gel spray is 0.1 - 16 Pas.

[0055] In a second aspect, the present invention also provides a preparation method of a fast film-forming nystatin oral gel spray for preparing the above-mentioned fast film-forming nystatin oral gel spray. The preparation method includes:

[0056] Mixing a polyethylene glycol-polyvinyl alcohol graft copolymer, xanthan gum with a part of the solvent to obtain solution A;

[0057] Mixing glycerol, nystatin with the remaining solvent to obtain solution B;

[0058] Mixing solution A and solution B to obtain the fast film-forming nystatin oral gel spray.

[0059] Specifically, the step of mixing the polyethylene glycol-polyvinyl alcohol graft copolymer, xanthan gum with a part of the solvent to obtain solution A includes: adding the polyethylene glycol-polyvinyl alcohol graft copolymer to a part of the solvent, heating and stirring to dissolve, then adding the flavoring agent, preservative and xanthan gum, and stirring until dissolved to a uniform state to obtain solution A.

[0060] Exemplarily, the amount of the part of the solvent is such that the concentration of the polyethylene glycol-polyvinyl alcohol graft copolymer in solution A is 0.5 to 6% (for example, 1%, 2%, 3%, 4%, 5%), and the concentration of xanthan gum is 0.2 to 2% (for example, 0.3%, 0.5%, 0.7%, 1%, 1.2%, 1.5%, 1.8%).

[0061] Exemplarily, the heating temperature is 35 to 55 °C, such as 40 °C, 45 °C, 50 °C.

[0062] Specifically, mixing glycerol, nystatin with the remaining solvents to obtain Solution B includes: adding glycerol and solubilizer to the remaining solvents in sequence, stirring evenly, then adding nystatin, with a homogenization speed of 5000 - 8000 revolutions per minute and a homogenization time of 10 - 20 minutes to make the drug disperse evenly and obtain Solution B.

[0063] Specifically, mixing Solution A and Solution B includes: mixing Solution A and Solution B, with a homogenization speed of 6000 - 12000 revolutions per minute and a homogenization time of 20 - 30 minutes to make the two phases mix evenly and obtain the fast film - forming nystatin oral gel spray.

[0064] The present invention uses the homogenization method to prepare the fast film - forming nystatin oral gel spray, which is not prone to layering and sedimentation when placed at normal temperature or low temperature.

[0065] During implementation, filling the obtained fast film - forming nystatin oral gel spray into a spray container can obtain the fast film - forming nystatin oral gel spray product.

[0066] During use, directly spraying the drug gel of the spray product onto the oral affected area, and the gel forms a film in a short time and slowly releases the drug.

[0067] Next, the fast film - forming nystatin oral gel spray of the present invention and its preparation method will be further described through specific examples.

[0068] Example 1

[0069] This example provides a fast film - forming nystatin oral gel spray with a total mass of 100 g. Among them, the nystatin content is 1.0 g, the xanthan gum (relative molecular weight is 2×10 6 Daltons) content is 1.0 g, the glycerol content is 10.1 g, the Tween 80 content is 1.1 g, the polyvinyl alcohol - polyethylene glycol copolymer (molecular weight is 45000 Daltons, the content of polyvinyl alcohol units is 75%, and the content of polyethylene glycol units is 25%) content is 5.0 g, the sucrose content is 19.8 g, the sucralose content is 0.2 g, the sodium benzoate content is 0.14 g, and the rest is purified water.

[0070] Example 2

[0071] This example provides a fast film - forming nystatin oral gel spray with a total mass of 100 g. Among them, the nystatin content is 1.0 g, the xanthan gum (relative molecular weight is 2×10 6Nystatin content: 0.8 g, glycerol content: 9.9 g, Tween 80 content: 1.1 g, polyvinyl alcohol-polyethylene glycol copolymer (molecular weight 45,000 Daltons, polyvinyl alcohol unit content 75%, polyethylene glycol unit content 25%) content: 5.0 g, sucrose content: 20.1 g, sodium benzoate content: 0.13 g, the balance being purified water.

[0072] Example 3

[0073] This example provides a fast film-forming nystatin oral gel spray similar to Example 1, except that the mass content of the polyethylene glycol-polyvinyl alcohol graft copolymer is 0.4%.

[0074] Example 4

[0075] This example provides a fast film-forming nystatin oral gel spray similar to Example 1, except that the mass content of xanthan gum is 0.1%.

[0076] Example 5

[0077] This example provides a fast film-forming nystatin oral gel spray similar to Example 1, except that the mass content of glycerol is 22%.

[0078] Example 6

[0079] This example provides a fast film-forming nystatin oral gel spray similar to Example 1, except that the drug loading of nystatin is 4.5%.

[0080] Example 7

[0081] This example provides a fast film-forming nystatin oral gel spray similar to Example 1, except that the mass ratio of xanthan gum, polyethylene glycol-polyvinyl alcohol graft copolymer, glycerol and nystatin is 3:4:15:1.

[0082] Example 8

[0083] This example provides a preparation method of the fast film-forming nystatin oral gel spray of Example 1, comprising:

[0084] Adding the polyethylene glycol-polyvinyl alcohol graft copolymer to a part of the solvent, heating and stirring to dissolve, then adding xanthan gum, and stirring until dissolved to a homogeneous state to obtain Solution A. The amount of the part of the solvent is such that the concentration of the polyethylene glycol-polyvinyl alcohol graft copolymer in Solution A is 3% and the concentration of xanthan gum is 2%. The heating temperature is 55°C.

[0085] Add glycerol, solubilizer, flavoring agent and preservative to the remaining solvent in sequence. After stirring evenly, add nystatin. The homogenization speed is 6000 revolutions per minute and the homogenization time is 15 minutes to disperse the drug evenly, obtaining Solution B.

[0086] Mix Solution A and Solution B with a homogenization speed of 8000 revolutions per minute and a homogenization time of 25 minutes to make the two phases mix evenly, obtaining a fast film-forming nystatin oral gel spray.

[0087] Comparative Example 1

[0088] This comparative example provides a fast film-forming nystatin oral gel spray similar to Example 1, except that polyethylene glycol-polyvinyl alcohol graft copolymer is not added.

[0089] Comparative Example 2

[0090] This comparative example provides a fast film-forming nystatin oral gel spray similar to Example 1, except that chitosan is used instead of xanthan gum.

[0091] Comparative Example 3

[0092] This comparative example provides a fast film-forming nystatin oral gel spray similar to Example 1, except that hydroxyethyl cellulose is used instead of xanthan gum.

[0093] Comparative Example 4

[0094] This comparative example provides a fast film-forming nystatin oral gel spray similar to Example 1, except that poloxamer is used instead of xanthan gum.

[0095] Comparative Example 5

[0096] This comparative example provides a fast film-forming nystatin oral gel spray similar to Example 1, except that polyvinyl alcohol is used instead of polyethylene glycol-polyvinyl alcohol graft copolymer.

[0097] Prepare the nystatin oral gel sprays of Examples 2 - 7 and Comparative Examples 1 - 5 according to the method of Example 8, except that the single conditions of Examples 2 - 7 and Comparative Examples 1 - 5 are changed respectively.

[0098] Detect the various performances of the obtained nystatin oral gel sprays of Examples 1 - 7 and Comparative Examples 1 - 5.

[0099] Among them, the film-forming performance detection method: evenly coat the preparation thinly on a glass slide, start timing, and the time until the gel adheres to the glass slide to form a film is the film-forming time; place the glass slide with the formed film in a beaker filled with purified water, and time until the film completely detaches from the glass slide, which is the film rupture time.

[0100] The method for detecting the gel viscosity is as follows: Use a digital display viscometer and a No. 2 rotor, and record the viscosity values of each gel.

[0101] The method for detecting sprayability is as follows: Fill the prepared gel into a spray device, press the pump head, and record the liquid spraying situation.

[0102] The film-forming performance, gel viscosity, and sprayability test results are shown in Table 1:

[0103] Table 1

[0104]

[0105] As can be seen from Table 1, compared with Example 1, in Example 3, the content of polyethylene glycol-polyvinyl alcohol graft copolymer decreases, which will prolong the spray film-forming time; compared with Example 1, in Example 4, the content of xanthan gum is lower, which enhances the gel fluidity, reduces the adhesiveness, and shortens the film body rupture time; compared with Example 1, in Example 5, the mass content of glycerol increases, which will increase the gel viscosity, change the rheological properties, and thus change the gel spraying resistance, and at the same time also affects the film-forming performance; compared with Example 1, in Example 6, the drug loading is too large, which will lead to a decrease in the dispersibility of the drug in the gel matrix, thus affecting the film-forming performance and gel viscosity; compared with Example 1, in Example 7, the proportion of xanthan gum content increases, which will increase the gel viscosity, and thus change the gel spraying resistance, and at the same time also affects the film-forming performance.

[0106] The method for detecting drug release is as follows: Using PBS as the release medium, conduct a release study. Weigh 300 mg precisely into the diffusion cell, and respectively draw the release medium at 0.5, 1, 2, 3, 4, 6, 24, 36, and 48 h, measure the drug concentration, calculate the cumulative release amount, and the release degree is expressed as a percentage. The results are as follows in the table.

[0107] The drug release test results are shown in Table 2 and Figure 1 ( Figure 1 is the drug release curve of the fast film-forming nystatin oral gel spray of Example 1) as shown:

[0108] Table 2

[0109]

[0110] As can be seen from Table 2, the drug release percentage of the fast film-forming nystatin oral gel spray of the present invention is more than 45% within 48 hours. It should be noted that although the release percentage of Example 4 is the highest, it is not that the higher the release amount is, the better. If the release amount is too high, it will affect the sustained release property. Therefore, the content of xanthan gum is preferably 0.2 - 2%. Although the drug release percentage of Example 6 is relatively high within 48 hours when the drug loading amount of nystatin is 4.5%, considering the data in Table 3, due to the too large drug loading amount in Example 6, the dispersibility and stability of the fast film-forming nystatin oral gel spray are both reduced. Therefore, considering comprehensively, the drug loading amount of nystatin is preferably 0.8 - 4%.

[0111] The detection method for drug dispersibility is: visual method. After standing under different storage conditions, observe the gel properties and whether there is drug precipitation at the bottom of the gel solution. Figure 2 Only partial gel photos are shown. For the specific results, please refer to Table 3.

[0112] The detection method for gel stability is: visually observe the gel properties, whether the gel solution changes color, and whether there is drug sedimentation at the bottom, etc., and quantitatively detect the drug content in the gel solution under different storage conditions. Figure 3 Only partial gel photos are shown. For the specific results, please refer to Table 3.

[0113] The detection results of drug dispersibility and gel stability are shown in Table 3 as follows:

[0114] Table 3

[0115]

[0116]

[0117] As can be seen from Table 3, when comparing Example 6 with Example 1, when the drug loading amount is too large, it has an impact on both the drug dispersibility and stability; when other gel matrices are used to replace xanthan gum in Comparative Examples 2, 3, and 4, it has an impact on both the drug stability and dispersibility.

[0118] The above is only the preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any changes or substitutions that can be easily thought of by those skilled in the art within the technical scope disclosed by the present invention should be covered by the protection scope of the present invention.

Claims

1. A fast film-forming nystatin oral gel spray, characterized in that: The fast film-forming nystatin oral gel spray comprises nystatin, xanthan gum, polyethylene glycol-polyvinyl alcohol graft copolymer, glycerol and a solvent, wherein the solvent is water; Based on the total mass of the fast film-forming nystatin oral gel spray, the mass content of the polyethylene glycol-polyvinyl alcohol graft copolymer is 0.4-5%, the mass content of the xanthan gum is 0.1-1%, the mass content of the glycerol is 8-11%, and the drug loading of the nystatin is 1-4.5%; The molecular weight of the polyethylene glycol-polyvinyl alcohol graft copolymer is 40,000 to 50,000 Daltons; the relative molecular weight of the xanthan gum is 1×10 6 ~3×10 6 .

2. The fast film-forming nystatin oral gel spray according to claim 1, characterized in that: The mass ratio of the xanthan gum, the polyethylene glycol-polyvinyl alcohol graft copolymer, the glycerol and the nystatin is (0.01-5):(0.025-10):(1.25-25):

1.

3. The fast film-forming nystatin oral gel spray according to claim 1, characterized in that: The fast film-forming nystatin oral gel spray further comprises a solubilizer, which is Tween 80 and / or lecithin; And / or, the fast film-forming nystatin oral gel spray further comprises a flavoring agent and a preservative.

4. The fast film-forming nystatin oral gel spray according to claim 1, characterized in that: The pH of the fast film-forming nystatin oral gel spray is 5.4-6.5; And / or, the fast film-forming nystatin oral gel spray has a gel viscosity of 0.1-16 Pas.

5. A method for preparing a fast film-forming nystatin oral gel spray, for preparing the fast film-forming nystatin oral gel spray according to any one of claims 1 to 4, characterized in that: The preparation method comprises: Mixing polyethylene glycol-polyvinyl alcohol graft copolymer, xanthan gum and part of solvent to obtain liquid A; Mix glycerol, nystatin and other solvents to obtain solution B; Liquid A and liquid B are mixed to obtain a fast film-forming nystatin oral gel spray.

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