Low-dose nicotine dry powder composition for inhalation

Abstract

The present invention provides an inhalable nicotine dry powder composition comprising nicotine powder and fragrance powder, wherein the nicotine powder comprises nicotine or a nicotine salt, amino acids, and excipients, the fragrance powder comprises flavoring agents and excipients, and the nicotine content is less than 0.5% by weight of the total dry powder composition, and a method for producing the same.

Description

Technical Field

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[0005]

[0001] The present invention relates to a low-volume nicotine dry powder composition for inhalation.

Background Art

[0002] Nicotine is transmitted into the body in various ways, such as by inhaling combustion-type tobacco such as cigarettes, cigars, and pipe tobacco, by using a method in which an aerosol is generated by heating an aerosol product substance in a cigarette, or by directly inhaling nicotine powder or the like.

[0003] Among them, the method of directly inhaling nicotine powder is to directly deliver it to the user's airway by inhaling dry powder using a dry powder inhaler (DPI). The dry powder contains various active ingredients (drugs) in addition to nicotine for the purpose of improving diseases and the like.

[0004] However, conventional nicotine dry powder for inhalation has a nicotine content of 1 to 10% by weight, but has a side effect of inducing coughing during inhalation. The coughing induced during inhalation induces the discharge of inhaled active ingredients and the like, and there is a problem that the designed function cannot be fully obtained.

Summary of the Invention

[0007] According to one embodiment of the present invention, an inhalation nicotine dry powder composition comprising nicotine powder and fragrance powder, The nicotine powder comprises nicotine or nicotine salt, amino acids, and excipients. The aforementioned fragrance powder contains a flavoring agent and an excipient. The present invention provides an inhalable nicotine dry powder composition characterized in that the nicotine content is less than 0.5% by weight of the total dry powder composition. [Effects of the Invention]

[0008] When using an inhalable nicotine dry powder composition according to one aspect of the present invention, cough induction is suppressed, the excretion of inhaled active ingredients is suppressed, and the user can obtain the designed functions of nicotine and active ingredients fully and efficiently, maximizing the satisfaction of nicotine and other substances. [Brief explanation of the drawing]

[0009] [Figure 1] This figure shows the spray drying process and conditions according to one embodiment of the present invention. [Figure 2] This figure shows the jet milling process and conditions according to one embodiment of the present invention. [Figure 3] This graph shows the evaluation results of the NGI (Next Generation Impactor) test, a standard device for evaluating pharmaceutical inhalants, for nicotine content of 0.99% by weight, 0.74% by weight, and 0.5% by weight, respectively. [Figure 4] This figure shows the results of measuring the amount of nicotine transferred from each puff of a nicotine dry powder composition according to one embodiment of the present invention. [Modes for carrying out the invention]

[0010] The embodiments will be described in detail below with reference to the attached drawings. However, various modifications may be made to the embodiments, and the scope of the patent application will not be limited or restricted by such embodiments. All modifications, equivalents, or substitutes to the embodiments should be understood to be included within the scope of the patent.

[0011] The terms used in the embodiments are for illustrative purposes only and should not be construed as intended to limit them. Singular expressions include plural expressions unless the context clearly indicates otherwise. In this specification, terms such as “includes” or “having” indicate the presence of features, figures, steps, actions, components, parts, or combinations thereof described in the specification, and should not be understood as preemptively excluding the possibility of the presence or addition of one or more other features, figures, steps, actions, components, parts, or combinations thereof.

[0012] Unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as those generally understood by a person of ordinary skill in the art to which this embodiment belongs. Commonly used, predefined terms should be interpreted as having the meaning consistent with their meaning in the context of the relevant art, and not as ideal or overly formal unless expressly defined herein.

[0013] Furthermore, when explaining with reference to the attached drawings, the same components will be assigned the same reference numerals regardless of the reference numerals used in the drawings, and redundant explanations will be omitted. In the description of embodiments, if a specific explanation of related prior art is deemed to unnecessarily obscure the gist of the embodiment, such detailed explanation will be omitted.

[0014] In addition, when describing the components of the embodiments, terms such as first, second, A, B, (a), (b), etc. can be used. These terms are for distinguishing the components from other components, and the essence, order, or sequence of the components are not limited by these terms.

[0015] Components including functions common to components included in any of the embodiments will be described using the same names in other embodiments. Unless otherwise stated, the descriptions given in any of the embodiments apply to other embodiments as well, and specific descriptions within the overlapping scope will be omitted.

[0016] As used herein, the term "dry powder inhaler" refers to a device that transmits substances such as those generated by the reaction of a nicotine-related substance and an organic acid substance into the user's lungs through the user's mouth.

[0017] According to one embodiment of the present invention, there is provided a nicotine dry powder composition for inhalation, comprising nicotine powder and fragrance powder. <​​​​​​​​​​​​​​​​​​​​​Here, the nicotine salt exists in the form of a salt of nicotine and an organic acid, and the organic acid corresponds to, but is not limited to, lactic acid, tartaric acid, pyruvic acid, benzoic acid, citric acid, and / or salicylic acid.

[0024] When forming an organic acid and a nicotine salt as described above, for example, it may have the form of nicotine lactate, nicotine tartrate, nicotine pyruvate, or nicotine salicylate. Among them, in terms of the use of the nicotine powder in the nicotine dry powder composition for human inhalation, the organic acid is a metabolite in the body but is non-toxic and harmless to the human body, and not only has the advantage that it is easy to decompose and excrete even when absorbed by the human body, but also has no adverse effect on the sensory characteristics, and is preferably lactic acid that has no particular dislike. Therefore, the nicotine salt is preferably nicotine lactate.

[0025] In addition to the nicotine or nicotine salt, the nicotine powder may also contain an amino acid and an excipient.

[0026] The type of amino acid is not greatly restricted, but corresponds to one or more of leucine, lysine, valine, arginine, threonine, phenylalanine, glycine, and / or methionine. Preferably, the amino acid may contain leucine.

[0027] Thus, when leucine is included as an amino acid, different from the case of other amino acids, leucine has hydrophobicity and thus is distributed on the outer skin side of the powder during powder formation, improving the fluidity of the finally formed nicotine dry powder composition, and thereby the transfer amount can be improved.

[0028] Furthermore, it is preferable that the amino acid content at this time be 5% by weight or less based on the total dry powder. By adjusting the amino acid content to 5% by weight or less as described above, the particle size and particle size distribution of the final nicotine dry powder composition can be improved, and it may also meet the FDA approval requirements for leucine content.

[0029] The excipients contained in the nicotine powder may include sugars and / or sugar alcohols, and the types of sugars may include sucrose, trehalose, dextrose, glucose, maltose, etc. Furthermore, the types of sugar alcohols may include mannitol, sorbitol, galactitol, maltitol, xylitol, lactitol, etc.

[0030] Of these, the excipient preferably contains mannitol, which has advantages when formulated by spray drying. Specifically, mannitol is water-soluble, stable in water before and after formulation, has no particularly negative sensory characteristics other than a slight sweetness, and has no special side effects, making it particularly advantageous to use as a carrier substance for delivering nicotine. Furthermore, mannitol has the advantage of binding to sputum and other substances in the bronchi when absorbed into the bronchi, thereby facilitating their excretion.

[0031] On the other hand, the inhalation nicotine dry powder composition according to one embodiment of the present invention includes a fragrance powder as a further constituent element, and the fragrance powder will be described in detail below.

[0032] The fragrance powder comprises a flavoring agent and an excipient, the flavoring agent being a fragrance commonly used in smoking articles and the like, and including, but not limited to, rosemary, eucalyptus, licorice, sucrose, fructose syrup, isosweeteners, cocoa, lavender, cinnamon, cardamom, celery, fenugreek, cascarilla, sandalwood, bergamot, geranium, honey essence, rose oil, vanilla, lemon oil, orange oil, mint oil, mandarin oil, catechin, grapefruit, caraway, cognac, jasmine, cacao, menthol, cinnamon, ylang-ylang, salvia, spearmint, ginger, coriander, coffee, and the like.

[0033] Furthermore, by including a flavoring agent in the aforementioned fragrance powder, it is possible not only to provide users with a sense of flavor, but also, selectively depending on the type of flavoring agent, to exert not only a role as a fragrance but also cough suppression functions such as dilating the bronchi. From this perspective, it is preferable that the flavoring agent includes menthol.

[0034] Furthermore, as with the nicotine powder described earlier, the flavor powder may also contain excipients. As for the types of excipients, as mentioned above, they may include sugars such as sucrose, trehalose, dextrose, glucose, and maltose, and / or sugar alcohols such as mannitol, sorbitol, galactitol, maltitol, xylitol, and lactitol. Of these, mannitol is preferred as the excipient.

[0035] The inhalation nicotine dry powder composition according to one embodiment of the present invention may contain nicotine powder and fragrance powder in a weight ratio of 9:1 to 5:5, preferably in a weight ratio of 8:2 to 6:4.

[0036] By adjusting the nicotine powder and flavor powder within the above-mentioned range, the aerodynamic transfer characteristics of the powder can be adjusted. In particular, the particle size, particle distribution, and transfer characteristics of the powder are good, and the user can fully satisfy the functions of nicotine and flavor. Specifically, when the weight ratio of nicotine powder to flavor powder exceeds 9:1 (e.g., 10:1), the impact sensation on the upper bronchi is reduced. When the weight ratio of nicotine powder to flavor powder is less than 5:5 (e.g., 4:6), the particles tend to become larger, which may make it difficult for the flavor particles to attract and transfer nicotine particles to the inside of the bronchi.

[0037] Furthermore, from the perspective of suppressing cough induction in the user, it is preferable that the nicotine content ultimately contained in the inhalable nicotine dry powder composition be less than 0.5%. If the nicotine content is higher than this, the efficiency of nicotine use (inhalation) may decrease compared to the amount of nicotine supplied through cough induction.

[0038] On the other hand, the inhalation nicotine dry powder composition according to one embodiment of the present invention may further contain cough suppression components in addition to the nicotine powder and fragrance powder described in detail above. Such cough suppression components are not particularly limited, but examples include menthol, mint, saccharin, and benzocaine.

[0039] Thus, even when the inhalation nicotine dry powder composition separately contains a cough-suppressing component, in order to exhibit the effects according to one embodiment of the present invention, the nicotine content, or the amino acid content, and the weight ratio of nicotine powder and fragrance powder must satisfy the preferred range described above.

[0040] According to one embodiment of the present invention, a method for producing a nicotine dry powder composition for inhalation is provided, The nicotine powder is produced by the step (S1) of manufacturing nicotine powder containing nicotine or a nicotine salt, amino acids, and excipients; Step (S2) to produce a flavor powder containing flavoring agents and excipients; and Step (S3): Mix the nicotine powder and the fragrance powder in a weight ratio of 8:2 to 6:4. Includes, The present invention provides a method for producing a nicotine dry powder composition for inhalation, characterized in that the nicotine content is less than 0.5% by weight of the total dry powder composition.

[0041] The composition and types of nicotine powder and flavor powder produced in each step of the above manufacturing method are considered to be substantially the same as those described in detail earlier, and each step of the manufacturing method is specifically described below.

[0042] Step S1 is a step in producing nicotine powder containing nicotine or nicotine salts, amino acids, and excipients, and is specifically produced through a spray drying process.

[0043] During spray drying, water is used as the solvent and mixed with the constituent materials of the nicotine powder. The mixture is then spray-dried at an inlet temperature of approximately 100°C and a flow rate of approximately 2-7 mL / min to form the nicotine powder.

[0044] Subsequently, step S2 is a step in which a flavor powder containing flavoring agents and excipients is produced, specifically through a jet milling process.

[0045] During jet milling, it is preferable to lower the temperature to prevent it from rising. This is because at high temperatures, flavorings such as menthol easily volatilize, resulting in a decrease in their content in the powder or adversely affecting the transfer rate. Therefore, unlike nicotine powder, which is spray-dried at high temperatures, it is preferable to manufacture flavor powders in a separate step through low-temperature jet milling.

[0046] Subsequently, the nicotine powder and fragrance powder produced in step S3 are mixed (post-mixing) in a weight ratio of 8:2 to 6:4. This ensures that the nicotine and other components contained in the nicotine powder and the fragrance powder are evenly mixed without any component loss. The relatively larger fragrance particles act as carriers to ensure the nicotine particles are evenly transported, resulting in favorable transfer characteristics and other results when the user inhales.

[0047] The configuration of the present invention and its effects will be described in detail below through embodiments and comparative examples. However, these embodiments are intended to illustrate the present invention more specifically, and the scope of the present invention is not limited to these embodiments.

[0048] - Embodiment

[0049] 1. Manufacturing Example: Production of Inhalation Nicotine Dry Powder Composition

[0050] 1) Nicotine powder manufacturing - spray drying

[0051] Using water as a solvent, nicotine powder was produced using the spray drying process shown in Figure 1 and the process conditions shown in Table 2, with nicotine, lactic acid, mannitol, and leucine in the composition ratios shown in Table 1. [Table 1]

[0052] [Table 2]

[0053] *Process: Solid content (within 2%, room temperature aqueous solution)

[0054] 2) Manufacturing of fragrance powder - Jet milling

[0055] Fragrance powders were produced using the jet milling process (conditions) shown in Figure 2, according to the composition ratios shown in Table 3 below. Low-temperature milling was performed to prevent temperature increases during jet milling. [Table 3]

[0056] 3) Preparation of the final dried powder composition

[0057] The manufactured nicotine powder and flavor powder were mixed in a weight ratio of 6:4 to produce the final nicotine dry powder composition, and the composition ratio of the obtained nicotine dry powder composition is shown in Table 4 below. [Table 4]

[0058] 2. Test Example 1: Measurement of Particle Size and Particle Size Distribution

[0059] The dried powder compositions containing 0.50% nicotine, and those containing 0.74% and 0.99% nicotine, prepared as described above, were each evaluated using the NGI (Next Generation Impactor) test, a standard evaluation device for pharmaceutical inhalants. The results are shown in Figure 3. Furthermore, MMAD and FPF results were derived using the inhalatix program, and the results for the dried powder composition containing 0.50% nicotine are shown in Table 5 below. [Table 5]

[0060] On the other hand, the contents described in Figure 3 are as follows:

[0061] Device: Inhaler device

[0062] Adaptor: A holder that connects the inhaler device and the induction port.

[0063] Induction port: A device that mimics the human respiratory system as a component of NGI.

[0064] S1-S7: Impactor step to collect aerosols according to particle size using NGI.

[0065] MOC: The last part of the impactor

[0066] y-axis: Ratio of particles adsorbed at each site relative to the total amount of particles discharged (100%).

[0067] 3. Test Example 2: Evaluation of Transition Characteristics

[0068] The amount of nicotine transferred during 14 puffs after applying the nicotine dry powder composition prepared above to a tube filter is shown (Figure 4).

[0069] Since the total transfer amount can be considered good when the amount is 25 mg or more based on a filling amount of 30 mg, it can be seen that the nicotine dry powder composition according to one embodiment of the present invention has good transfer characteristics.

[0070] Although embodiments of the present invention have been described in detail above with reference to the drawings, a person with ordinary skill in the art can apply various technical modifications and variations based on the above. For example, the described techniques may be performed in a different order than described, and / or the components of the described systems, structures, devices, circuits, etc. may be combined or assembled in a different manner than described, and substituted or replaced by other components or equivalents, while still achieving the desired results.

[0071] Therefore, other embodiments, other examples, and those equivalent to the claims described below also fall within the scope of the claims.

Claims

1. A nicotine dry powder composition for inhalation, comprising nicotine powder and fragrance powder, The nicotine powder comprises nicotine or nicotine salt, amino acids, and excipients. The aforementioned fragrance powder contains a flavoring agent and an excipient. A nicotine dry powder composition for inhalation, characterized in that the nicotine content is less than 0.5% by weight of the total dry powder composition.

2. The inhalation nicotine dry powder composition according to claim 1, characterized in that the weight ratio of the nicotine powder to the fragrance powder is 8:2 to 6:

4.

3. The nicotine salts mentioned above are Nicotine and, The inhalation nicotine dry powder composition according to claim 1, comprising a salt containing one or more selected from the group consisting of lactic acid, tartaric acid, pyruvic acid, benzoic acid, citric acid, and salicylic acid.

4. The nicotine salt comprises nicotine and lactic acid, as described in claim 1, for inhalation.

5. The inhalation nicotine dry powder composition according to claim 1, wherein the amino acid comprises one or more selected from the group consisting of leucine, lysine, valine, arginine, threonine, phenylalanine, chrysin, and methionine.

6. The inhalation nicotine dry powder composition according to claim 1, wherein the aforementioned amino acid is leucine.

7. The inhalation nicotine dry powder composition according to claim 1, wherein the content of the amino acids is 5% by weight or less of the total dry powder composition.

8. The excipient comprises one or more of sugars and sugar alcohols. The aforementioned sugar comprises one or more selected from the group consisting of lactose, sucrose, trehalose, dextrose, glucose, and maltose. The inhalation nicotine dry powder composition according to claim 1, wherein the sugar alcohol comprises one or more selected from the group consisting of mannitol, sorbitol, galactitol, maltitol, xylitol, and lactitol.

9. The inhalation nicotine dry powder composition according to claim 1, wherein the excipient comprises mannitol.

10. The inhalation nicotine dry powder composition according to claim 1, wherein the flavoring agent comprises one or more selected from the group consisting of rosemary, eucalyptus, licorice, sucrose, fructose syrup, isosweet, cocoa, lavender, cinnamon, cardamom, celery, fenugreek, cascarilla, sandalwood, bergamot, geranium, honey essence, rose oil, vanilla, lemon oil, orange oil, mint oil, mandarin oil, catechin, grapefruit, caraway, cognac, jasmine, cacao, menthol, cinnamon, ylang-ylang, salvia, spearmint, ginger, coriander, and coffee.

11. The inhalation nicotine dry powder composition according to claim 1, further comprising a cough suppressant.

12. The inhalable nicotine dry powder composition according to claim 11, wherein the cough-suppressing component comprises one or more of menthol, mint, saccharin, and benzocaine.

13. A method for producing a nicotine dry powder composition for inhalation, The nicotine powder is produced by a step (S1) of manufacturing a nicotine powder containing nicotine or a nicotine salt, an amino acid, and an excipient. Step (S2) for producing a flavor powder containing flavoring agents and excipients, The steps include mixing the nicotine powder and the fragrance powder in a weight ratio of 8:2 to 6:4 (S3), Includes, A method for producing a nicotine dry powder composition for inhalation, characterized in that the nicotine content is less than 0.5% by weight of the total dry powder composition.

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