Nicotine buccal product for promoting transdermal absorption

Abstract

The invention discloses a nicotine buccal product for promoting transdermal absorption, and relates to the technical field of nicotine buccal products. The buccal nicotine product for promoting transdermal absorption contains a transdermal absorption enhancer, and the transdermal absorption enhancer is selected from at least one of peppermint oil, wintergreen oil, menthol, azone and derivatives thereof, and sucrose monolaurate. According to the invention, the transdermal absorption enhancer is added into the buccal product, and the lipid fluidity is increased by interfering a cuticle phospholipid bilayer structure, so that the partition coefficient of nicotine in oral mucosa is changed, and the purposes of increasing the nicotine permeation rate and enhancing the nicotine uptake experience are achieved.

Description

Technical Field

[0001] The invention relates to the technical field of nicotine oral products, in particular to a nicotine oral product capable of promoting transdermal absorption. Background Art

[0002] Under alkaline conditions, nicotine in snus actively diffuses into the oral mucosa in the form of free state, and the rate-limiting step in the process of nicotine migration to the brain's nicotinic acetylcholine receptors is the process of passing through the oral mucosa. In order to increase the migration rate of nicotine and improve the nicotine intake experience, existing oral products usually adopt methods such as increasing the pH of oral products and adding free nicotine. On the one hand, these methods have limited effects on improving the rate of getting high. On the other hand, due to the increase in alkali and free nicotine, it will cause negative effects such as yellowing of the product and a strong burning sensation on the lips. Summary of the invention

[0003] In order to solve the above technical problems, the present invention adds transdermal absorption enhancers to the formula of traditional oral tobacco products. These transdermal absorption enhancers interfere with the phospholipid bilayer structure of the stratum corneum and increase lipid fluidity, thereby changing the distribution coefficient of nicotine in the oral mucosa, thereby increasing the nicotine penetration rate and enhancing the nicotine intake experience.

[0004] The objective of the present invention is achieved through the following technical scheme: providing a nicotine oral preparation for promoting transdermal absorption, wherein the nicotine oral preparation contains a transdermal absorption enhancer, wherein the transdermal absorption enhancer is selected from at least one of peppermint oil, wintergreen oil, menthol, azone and its derivatives, and sucrose monolaurate.

[0005] Furthermore, the nicotine oral product for promoting transdermal absorption contains the following ingredients in parts by weight:

[0006] Resin nicotine 4-30 parts;

[0007] Filler 20-50 parts;

[0008]

[0009] Preferably, the pH of the aqueous solution of the nicotine oral product for promoting transdermal absorption at a mass ratio of 1:10 is controlled below 9.1, and more preferably, the pH is controlled at 8-9.1.

[0010] Preferably, the pH adjuster is selected from at least one of benzoic acid, sodium benzoate, sodium bicarbonate and sodium carbonate.

[0011] Preferably, the filler is selected from at least one of sodium microcrystalline cellulose, starch, maltitol, mannitol and sorbitol.

[0012] Preferably, the humectant is selected from at least one of glycerol and propylene glycol.

[0013] Preferably, the sweetener is selected from at least one of acesulfame potassium, sucralose and neotame.

[0014] Preferably, the antioxidant is selected from at least one of sodium sulfite, sodium metabisulfite, sodium thiosulfate, sodium ascorbate and tea polyphenols.

[0015] Preferably, the cooling agent is selected from at least one of WS-3, WS-5 and WS-23.

[0016] Preferably, the flavoring agent is selected from at least one of strawberry flavor, sweet orange flavor, watermelon flavor, lemon flavor, citrus flavor, blueberry flavor, tea flavor, mint flavor, and wintergreen flavor.

[0017] The preparation method of the nicotine oral product for promoting transdermal absorption of the present invention is as follows:

[0018] S1: Mix water, sweetener and sodium chloride to fully dissolve the sweetener and sodium chloride in the water;

[0019] S2: mixing the moisturizer, the transdermal absorption enhancer, and the cooling agent, so that the transdermal absorption enhancer and the cooling agent are fully dissolved in the moisturizer or form a uniform emulsion;

[0020] S3: mixing and stirring the liquids in steps S1 and S2 to form a uniform emulsion; adding filler, resin nicotine, pH adjuster, antioxidant, flavoring agent, and ammonium chloride to the emulsion in sequence, and mixing evenly to obtain a nicotine oral product that promotes transdermal absorption.

[0021] The present invention adds a transdermal absorption enhancer to the oral product to increase the penetration rate of nicotine and enhance the nicotine intake experience. Different transdermal absorption enhancers can be selected for different flavors. Menthol and / or mint oil, two natural ingredients, can be added to mint flavor and mint derivative flavor. On the one hand, they present a strong mint aroma and a refreshing cool feeling as a flavor corrector, and on the other hand, they can be used as a natural transdermal absorption enhancer to accelerate the absorption rate of nicotine; wintergreen flavors add wintergreen oil, a natural ingredient; fruit flavors can add odorless chemical transdermal absorption enhancers such as azone and its derivatives, and sucrose monolaurate to accelerate the absorption rate. Furthermore, using a relatively stable resin nicotine salt and controlling the pH of the oral product to be below 9.1 can avoid the problems of yellowing and strong lip burning caused by the increase of alkali and free nicotine in existing oral products. DETAILED DESCRIPTION

[0022] The technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0023] It should be understood that when used in this specification and the appended claims, the terms "include" and "comprises" indicate the presence of described features, integers, steps, operations, elements and / or components, but do not exclude the presence or addition of one or more other features, integers, steps, operations, elements, components and / or combinations thereof.

[0024] It should be further understood that the term "and / or" used in the present description and the appended claims refers to any and all possible combinations of one or more of the associated listed items, and includes these combinations.

[0025] Example 1

[0026] A mint-flavored nicotine oral product for promoting transdermal absorption: mint oil and menthol are used as flavors and also as transdermal absorption accelerators.

[0027] The preparation method of the nicotine oral product is as follows:

[0028] S1. Mix 20 g of water, 0.3 g of acesulfame potassium, and 1 g of sodium chloride, so that acesulfame potassium and sodium chloride are fully dissolved in water.

[0029] S2. Take another beaker and mix 8 g of propylene glycol, 0.5 g of menthol and 1 g of peppermint oil, so that the menthol and peppermint oil are fully dissolved in the propylene glycol.

[0030] S3. Mix the liquids in the beakers in S1 and S2, and stir to form a uniform emulsion; add 40g of microcrystalline cellulose, 16g of nicotine resin, 5g of sodium carbonate, 1g of sodium ascorbate, and 0.5g of ammonium chloride to the emulsion in that order, stir evenly, sieve, and bag at 0.55g.

[0031] Example 2

[0032] A menthol-flavored nicotine oral product for promoting transdermal absorption: menthol is used as a flavor and also as a transdermal absorption accelerator.

[0033] The preparation method of the nicotine oral product is as follows:

[0034] S1. Mix 20 g of water, 0.3 g of acesulfame potassium, and 1 g of sodium chloride, so that acesulfame potassium and sodium chloride are fully dissolved in water.

[0035] S2. Take another beaker and mix 8 g of propylene glycol and 2.5 g of menthol, so that the menthol is fully dissolved in the propylene glycol or forms a uniform emulsion.

[0036] S3. Mix the liquids in the beakers of S1 and S2 and stir to form a uniform emulsion. Add 40g of microcrystalline cellulose, 16g of nicotine resin, 5g of sodium carbonate, 1g of sodium ascorbate, and 0.5g of ammonium chloride to the emulsion in order, stir evenly, sieve, and bag according to 0.55g.

[0037] Example 3

[0038] A wintergreen-flavored nicotine oral product for promoting transdermal absorption: wintergreen oil is used as a flavor and also as a transdermal absorption accelerator.

[0039] The preparation method of the nicotine oral product is as follows:

[0040] S1. Mix 20 g of water, 0.3 g of acesulfame potassium, and 1 g of sodium chloride, so that acesulfame potassium and sodium chloride are fully dissolved in water.

[0041] S2. Take another beaker and mix 8 g of propylene glycol and 1 g of wintergreen oil so that the wintergreen oil is fully dissolved in the propylene glycol or forms a uniform emulsion.

[0042] S3. Mix the liquids in the beakers of S1 and S2 and stir to form a uniform emulsion. Add 40g of microcrystalline cellulose, 16g of nicotine resin, 5g of sodium carbonate, 1g of sodium ascorbate, and 0.5g of ammonium chloride to the emulsion in order, stir evenly, sieve, and bag according to 0.55g.

[0043] Example 4

[0044] A strawberry-flavored nicotine oral product for promoting transdermal absorption: strawberry powder flavor is used as a flavoring agent, and azone is used as a transdermal absorption accelerator.

[0045] The preparation method of the nicotine oral product is as follows:

[0046] S1. Mix 20 g of water, 0.3 g of acesulfame potassium, and 1 g of sodium chloride, so that acesulfame potassium and sodium chloride are fully dissolved in water.

[0047] S2. Take another beaker, mix 8g propylene glycol and 1g azone, so that the azone is fully dissolved in the propylene glycol or forms a uniform emulsion.

[0048] S3. Mix the liquids in the beakers of S1 and S2 and stir to form a uniform emulsion. Add 40g of microcrystalline cellulose, 16g of nicotine resin, 5g of sodium carbonate, 1g of sodium ascorbate, 3g of strawberry powder flavor, and 0.5g of ammonium chloride to the emulsion in order, stir evenly, sieve, and bag according to 0.55g.

[0049] Example 5

[0050] A citrus-flavored nicotine oral preparation for promoting transdermal absorption: citrus powder flavor is used as a flavoring agent, and sucrose monolaurate is used as a transdermal absorption accelerator.

[0051] The preparation method of the nicotine oral product is as follows:

[0052] S1. Mix 20 g of water, 0.3 g of acesulfame potassium, and 1 g of sodium chloride, so that acesulfame potassium and sodium chloride are fully dissolved in water.

[0053] S2. Take another beaker, mix 8 g of propylene glycol and 1 g of sucrose monolaurate, so that the sucrose monolaurate is fully dissolved in the propylene glycol or forms a uniform emulsion.

[0054] S3. Mix the liquids in the beakers of S1 and S2 and stir to form a uniform emulsion. Add 40g of microcrystalline cellulose, 16g of nicotine resin, 5g of sodium carbonate, 1g of sodium ascorbate, 3g of citrus powder flavor, and 0.5g of ammonium chloride to the emulsion in order, stir evenly, sieve, and bag according to 0.55g.

[0055] Example 6

[0056] A mint-flavored nicotine oral product for promoting transdermal absorption: mint oil is used as a flavor and also as a transdermal absorption accelerator.

[0057] The preparation method of the nicotine oral product is as follows:

[0058] S1. Mix 25 g of water, 1.5 g of sucralose, and 8 g of sodium chloride, so that acesulfame potassium and sodium chloride are fully dissolved in the water.

[0059] S2. Take another beaker and mix 15 g of glycerol, 5 g of peppermint oil, and 0.1 g of WS-3, so that the peppermint oil and WS-3 are fully dissolved in the glycerol.

[0060] S3. Mix the liquids in the beakers in S1 and S2, and stir to form a uniform emulsion; add 50g maltitol, 30g resin nicotine, 10g sodium benzoate, 10g sodium sulfite, and 2g ammonium chloride to the emulsion in that order, stir evenly, sieve, and bag at 0.55g.

[0061] Example 7

[0062] A watermelon-flavored nicotine oral product for promoting transdermal absorption: watermelon flavor is used as flavor, and azone is used as a transdermal absorption accelerator.

[0063] The preparation method of the nicotine oral product is as follows:

[0064] S1. Mix 22 g of water and 0.3 g of acesulfame potassium so that the acesulfame potassium is fully dissolved in the water.

[0065] S2. Take another beaker and mix 2g propylene glycol, 0.1g azone and 5g WS-3 to make azone and WS-3 fully dissolved in propylene glycol.

[0066] S3. Mix the liquids in the beakers in S1 and S2, and stir to form a uniform emulsion; add 20g mannitol, 4g resin nicotine, 0.1g benzoic acid, 0.2g sodium metabisulfite, 0.2g watermelon essence to the emulsion in that order, stir evenly, sieve, and bag at 0.55g.

[0067] Example 8

[0068] A blueberry-flavored nicotine oral preparation for promoting transdermal absorption: blueberry flavor is used as the flavor, and sucrose monolaurate is used as a transdermal absorption promoter.

[0069] The preparation method of the nicotine oral product is as follows:

[0070] S1. Mix 20 g of water, 0.3 g of neotame, and 1 g of sodium chloride, so that acesulfame potassium and sodium chloride are fully dissolved in the water.

[0071] S2. Take another beaker and mix 8 g of propylene glycol and 0.5 g of sucrose monolaurate to fully dissolve menthol and peppermint oil in propylene glycol.

[0072] S3. Mix the liquids in the beakers in S1 and S2, and stir to form a uniform emulsion; add 40g sorbitol, 16g resin nicotine, 5g sodium bicarbonate, 1g sodium thiosulfate, 10g blueberry flavor, and 0.5g ammonium chloride to the emulsion in that order, stir evenly, sieve, and bag at 0.55g.

[0073] Example 9

[0074] A mint-flavored nicotine oral product for promoting transdermal absorption: mint oil and menthol are used as flavors and also as transdermal absorption accelerators.

[0075] The preparation method of the nicotine oral product is as follows:

[0076] S1. Mix 25 g of water, 0.3 g of acesulfame potassium, and 5 g of sodium chloride so that acesulfame potassium and sodium chloride are fully dissolved in the water.

[0077] S2. Take another beaker and mix 10 g of propylene glycol, 1.5 g of menthol and 1 g of peppermint oil, so that the menthol and peppermint oil are fully dissolved in the propylene glycol.

[0078] S3. Mix the liquids in the beakers in S1 and S2, and stir to form a uniform emulsion; add 40g of microcrystalline cellulose, 25g of resin nicotine, 3g of sodium carbonate, 1g of sodium ascorbate, and 0.5g of ammonium chloride to the emulsion in that order, stir evenly, sieve, and bag at 0.55g.

[0079] Example 10

[0080] A wintergreen-flavored nicotine oral product for promoting transdermal absorption: wintergreen oil is used as a flavor and also as a transdermal absorption accelerator.

[0081] The preparation method of the nicotine oral product is as follows:

[0082] S1. Mix 20 g of water, 1.0 g of acesulfame potassium, and 3 g of sodium chloride so that acesulfame potassium and sodium chloride are fully dissolved in water.

[0083] S2. Take another beaker and mix 12 g of glycerol and 3 g of wintergreen oil so that the wintergreen oil is fully dissolved in the glycerol or forms a uniform emulsion.

[0084] S3. Mix the liquids in the beakers of S1 and S2 and stir to form a uniform emulsion. Add 40g of microcrystalline cellulose, 16g of nicotine resin, 5g of sodium carbonate, 1g of sodium ascorbate, and 0.5g of ammonium chloride to the emulsion in order, stir evenly, sieve, and bag according to 0.55g.

[0085] Comparative Example 1

[0086] The difference from Example 1 is that the peppermint oil and menthol in Example 1 are replaced by an equal weight of peppermint powder flavor.

[0087] Comparative Example 2

[0088] The difference from Example 2 is that the menthol in Example 1 is replaced by an equal weight of mint powder flavor.

[0089] Comparative Example 3

[0090] The difference from Example 3 is that the wintergreen oil in Example 3 is replaced by an equal weight of wintergreen powder essence.

[0091] Comparative Example 4

[0092] The difference with Example 4 is that the azone in Example 4 is replaced with propylene glycol of equal weight.

[0093] Comparative Example 5

[0094] The difference from Example 5 is that the sucrose monolaurate in Example 5 is replaced by an equal weight of propylene glycol.

[0095] Comparative Example 6

[0096] The difference from Example 1 is that the peppermint oil and menthol in Example 1 are replaced by an equal weight of peppermint powder flavor, and the amount of sodium carbonate added is 12 g.

[0097] Comparative Example 7

[0098] The difference from Example 2 is that the menthol in Example 1 is replaced by an equal weight of mint powder flavor, and the amount of sodium carbonate added is 12 g.

[0099] Comparative Example 8

[0100] The difference from Example 3 is that the wintergreen oil in Example 3 is replaced by an equal weight of wintergreen powder essence, and the amount of sodium carbonate added is 12 g.

[0101] Comparative Example 9

[0102] The difference from Example 4 is that the azone in Example 4 is replaced by an equal weight of propylene glycol, and the sodium carbonate addition amount is 12g.

[0103] Comparative Example 10

[0104] The difference from Example 5 is that the sucrose monolaurate in Example 5 is replaced by an equal weight of propylene glycol, and the added amount of sodium carbonate is 12 g.

[0105] Determination of nicotine head-on time: 10 sensory evaluators who are smokers and 10 sensory evaluators who are not smokers were selected to put the product between the upper lip and upper gum, and record the time from when the product was put into the mouth to when the nicotine was felt, i.e. the "head-on feeling". The average head-on time of the 20 evaluators was taken as the average head-on time of the product.

[0106] pH testing method: Take 1g of oral product powder, add 10g of distilled water, stir for 5 minutes, and then measure the pH value of the mixture, which is the pH value of the oral product.

[0107] The test results of the oral preparations of Examples 1-10 and Comparative Examples 1-10 are shown in Table 1.

[0108] Table 1 Test results of oral preparations of Examples 1-10 and Comparative Examples 1-10

[0109]

[0110] From the test results in Table 1, it can be seen that the oral products of Examples 1-10 and Comparative Examples 1-10, natural peppermint oil, menthol, and wintergreen oil are effective transdermal absorption enhancers. After replacing powder flavors and adding them to oral tobacco products, they can effectively accelerate the penetration of nicotine into the oral mucosa, and significantly improve the head speed, with the fastest increase of 70s. For fruit flavors, after adding azone and sucrose monolaurate transdermal absorption enhancers, the head speed has also been greatly improved, with the fastest increase of 76s. The pH of the oral products of Examples 1-10 is controlled below 9.1. It can be seen that the head speed improvement of the oral products of the present invention is not achieved by increasing the pH of the oral products, but by transdermal absorption enhancers.

[0111] The above is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can easily think of various equivalent modifications or replacements within the technical scope disclosed by the present invention, and these modifications or replacements should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention shall be based on the protection scope of the claims.

Claims

1. A nicotine oral product for promoting transdermal absorption, characterized in that: The invention contains a transdermal absorption enhancer, wherein the transdermal absorption enhancer is selected from at least one of peppermint oil, wintergreen oil, menthol, azone and its derivatives, and sucrose monolaurate.

2. The nicotine oral product for promoting transdermal absorption according to claim 1, characterized in that: Contains the following ingredients by weight: Water is 20-25 parts.

3. The nicotine oral product for promoting transdermal absorption according to claim 2, characterized in that: The pH of its aqueous solution with a mass ratio of 1:10 is below 9.

1.

4. The nicotine oral product for promoting transdermal absorption according to claim 3, characterized in that: The pH regulator is selected from at least one of benzoic acid, sodium benzoate, sodium bicarbonate and sodium carbonate.

5. The nicotine oral product for promoting transdermal absorption according to claim 2, characterized in that: The filler is selected from at least one of sodium microcrystalline cellulose, starch, maltitol, mannitol and sorbitol.

6. The nicotine oral product for promoting transdermal absorption according to claim 2, characterized in that: The humectant is selected from at least one of glycerol and propylene glycol.

7. The nicotine oral product for promoting transdermal absorption according to claim 2, characterized in that: The sweetener is selected from at least one of acesulfame potassium, sucralose and neotame.

8. The nicotine oral product for promoting transdermal absorption according to claim 2, characterized in that: The antioxidant is selected from at least one of sodium sulfite, sodium pyrosulfite, sodium thiosulfate, sodium ascorbate and tea polyphenols.

9. The nicotine oral product for promoting transdermal absorption according to claim 2, characterized in that: The cooling agent is selected from at least one of WS-3, WS-5 and WS-23.

10. The nicotine oral preparation for promoting transdermal absorption according to claim 2, wherein the flavoring agent is at least one selected from the group consisting of strawberry flavor, sweet orange flavor, watermelon flavor, lemon flavor, citrus flavor, blueberry flavor, tea flavor, mint flavor, and wintergreen flavor.

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