JP2011057701A - Method to give rapid alleviation for nicotine chewing gum user - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a nicotine chewing gum to stop smoking. <P>SOLUTION: The method alleviating the nicotine thirst of a user includes steps of providing at least one of a chewing gum including a tobacco alkaloid and alleviating the nicotine thirst of the user by chewing the chewing gum and transferring the tobacco alkaloid from the chewing gum to the body of user, wherein the chewing step of the chewing gum includes transfer of the tobacco alkaloid from the chewing gum to the user beyond the transfer threshold within about 0.5 to about 2.5 minutes from the start of the chewing step. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to relieving craving by chewing gum holding nicotine.

Craving or dependent:
The American medical and scientific communities agree that nicotine is dependent. Nicotine is consistent with both psychological and physiological indicators of dependence.

  Psychological—People who depend on something use it impulsively without paying attention to the negative health effects of life. One good example is a person who continues to smoke even while breathing using an oxygen tank because of the damage that smoking has done to his lungs.

  Physiological-Neuroscientists call anything that stimulates the brain's reward pathways dependent. Stimulating this neural circuit makes you feel better, so you will continue to do this to regain that sensation.

  If a smoker suddenly quits smoking, the body cannot function as before without drugs and the physiological action for nicotine remains for at least a short time. They experience irritation, anxiety, depression and a craving for nicotine.

  Over time, these signs and physiological changes subside. This is a time when alternative methods of nicotine delivery are indispensable for successful smoking cessation.

nicotine:
Nicotine usually makes up about 5% of tobacco plants by weight. Cigarettes contain 8 to 20 mg of nicotine, depending on the brand, but only about 1 mg is actually absorbed by the body when smoked.

  The effect of nicotine is short-lived, lasting only 40 minutes to 2 hours. This leads to people smoking regularly throughout the day to administer nicotine to themselves. Within 10 to 15 seconds of inhalation, most smokers are in the midst of the effects of nicotine.

  Other measures can be taken to relieve the cravings associated with the absence of nicotine in the blood.

  Many drug therapies have been developed or explored to help smokers stop smoking. A powerful one is nicotine replacement therapy. Nicotine replacement therapy requires administration of nicotine via an appropriate delivery system. Commercially available nicotine replacement products include nicotine transdermal patches, inhalers, nicotine nasal sprays or nicotine chewing gum. These types of products, like cigarettes, deliver nicotine to the blood by nicotine diffusion across the skin or mucosa.

  Nicotine transdermal patches release nicotine into the bloodstream through the skin. Every day, apply the patch to different areas of dry, clean, hairless skin and leave it for the time recommended on the label, usually one day of sleep. Using this product produces a constant low concentration of nicotine in the blood over the time it is applied.

  Nicotine nasal spray is drawn into the nose from a pumped bottle and passes through the lining of the nose and is absorbed into the bloodstream. This form of nicotine delivery system results in an increase in the concentration of nicotine in the blood, almost as fast as cigarettes.

  The nicotine inhaler enters the user's mouth through a mouthpiece attached to a plastic cartridge. This product is called an “inhaler” but does not deliver nicotine to the lungs like cigarettes do. Almost all nicotine goes to the mouth and throat, where it is absorbed through the mucosa.

  Nicotine chewing gum releases nicotine into the bloodstream through the lining or mucous membrane of the mouth. Unlike chewing chewing gums, nicotine gum requires a precise way to chew slowly until it feels slightly tingling or tastes like pepper, and then there is little taste or tingling. Place between cheek and gums. This cycle is usually repeated for about 30 minutes per gum. Available products slowly increase the blood concentration of nicotine during the first 10-15 minutes of chewing.

The elimination of such craving by chewing gum holding nicotine is well known in the art.
In the prior art, basically two different methods have been taken alone or in combination.

  The first approach was to formulate nicotine in the chewing gum and then match the chewing gum release to the desired total nicotine release over the entire chewing time. Typically, such efforts require consideration regarding the release of nicotine over the day compared to one or several different smoking patterns.

  A further attempt to improve the elimination of craving by chewing gum is, for example, the incorporation of nicotine in the coating of the coated chewing gum. Such a method is sometimes referred to in the art as a two-step method, i.e., providing a large initial amount of nicotine immediately after starting to chew the chewing gum followed by a second long-term amount. is there. Such subsequent administration, also referred to as maintenance administration, lasts for about 10 to 30 minutes, for example by chewing.

  However, a problem with the prior art is that some users of chewing gum are particularly reluctant to administer the initial dose, and subsequent doses do not meet the user's expectations for alleviating the craving normally associated with nicotine.

International Publication No. 00/25598 US Patent Application No. 2004/0115305 US Pat. No. 6,627,234

Food and Drug Administration, CFR, Title 21, Section 172615 US Code Vol. 21, 182: 5013, 182: 5997, and 182: 8013-182: 8997 Martindale, The Extra Pharmacopoeia, 28th edition, pp. 547-578 J. et al. Dent. Res. 28, 2, 160-171, 1949 Barney H. Hunter and Robert L. Talbert, Pharm. Int. Nov. 85, 267-271 European Pharmacopeia 4 th. ed. 2.9.25 “Chewing gum medicated, drug release from”

  The object of the present invention is to obtain a chewing gum which is effective not only after use but also during use and which can be applied to relieve craving which is acceptable to the user.

  The present invention provides the step of providing at least one chewing gum containing tobacco alkaloid to the user, and moving the tobacco alkaloid from the chewing gum to the user's human body by chewing the chewing gum. Providing the user with relief from nicotine craving, the chewing gum being chewed at a time of about 0.5 minutes to about 2.5 minutes from the start of the chewing process. It relates to a method for reducing nicotine craving, characterized in that it comprises the chewing process with transfer of the tobacco alkaloid from the chewing gum exceeding a transfer rate.

  According to the present invention, the movement of nicotine or generally tobacco alkaloids is maintained at a migration rate threshold in the middle stage of the chewing process, whereby the movement at this particular time affects the perception of nicotine, e.g. It promotes advantageous and effective rapid relaxation due to the fact that it provides significant relaxation compared to nicotine migration later in the process. The preferred "rising onset" according to the present invention is the time that is usually overlooked in the chewing process, also referred to as the intermediate stage, because this particular time is within the normal time range for smoking a cigarette. It should be particularly noted that it encompasses providing a very important part of the desired nicotine administration to the human body.

  The migration rate threshold in the present invention is understood as the minimum migration rate of nicotine in a predetermined time interval. In other words, a movement rate exceeding this minimum speed may be applied for 2.5 minutes, ie 150 seconds, within the scope of the present invention.

  According to the present invention, one of the problems with the prior art has been realized that chewing gum user relief is obtained little or at least slowly compared to cigarette smoking. Also, what the prior art provides for this issue is usually concerned with the amount of nicotine released from the chewing gum, and basically there is little consideration on how the actual nicotine transfer takes place. I also noticed that I was not paid. This is both true for conventional extended release based on chewing time over about 30 minutes and for example for rapid nicotine release from the coating. Thus, for example, the very rapid release of nicotine in the first few seconds from the coating is due to the fact that most of this nicotine is swallowed and moves only to metabolism through the first 5 to 10 minutes. I noticed that it seemed to have too little influence on the chewing.

  According to the present invention, the transfer rate should be understood as the transfer rate, or release rate, of nicotine or tobacco alkaloids from the chewing gum to the outside, but the basic desirable performance of the chewing gum is the blood of the human body concerned from the chewing gum. Including moving to. Such a release rate may be measured in a partial time, for example 30 seconds.

  In the present invention, “tobacco alkaloid” means nicotine-like alkaloids such as nicotine or nornicotine, lobeline in the form of a free base or a pharmacologically acceptable acid addition salt. Plant alkaloids of this type are obtained from Nicotiana species, which are sources of nicotine and nornicotine, and from Lobelia species and Lobeliaceae (Indo tobacco) species, which are sources of lobeline.

Furthermore, the specific examples and explanations specifically referring to nicotine as an active substance against cravings in no way reduce the scope of the present invention with respect to the use of other tobacco alkaloids for the same specific purpose. Is generally noted. Specific references to nicotine in any part of this application are only used for the purpose of illustrating the invention in a clear manner and are used for the purpose of excluding functionally equivalent alternatives. It is not something.
It should generally be noted that nicotine is a preferred tobacco alkaloid.

  In the present invention, the term nicotine means, for example, amorphous, crystalline, polycrystalline or other physical forms or isomers and optical isomers thereof, as well as pharmaceutically acceptable salts, complexes or solvates. It includes any form of nicotine or nicotine derivative, such as a chemical form. Nicotine can be selected from nicotine zinc chloride and nicotine salicylate, such as nicotine base, nicotine hydrochloride, nicotine dihydrochloride, nicotine mononitrate, nicotine ditartrate, nicotine sulfate, nicotine zinc chloride monohydrate .

In one embodiment of the invention, the tobacco alkaloid comprises nicotine.
In one embodiment of the invention, the migration rate relates to the movement of nicotine from the chewing gum to the outside of the chewing gum.

  According to an advantageous embodiment of the invention, the chewing time can be significantly reduced for two different reasons. First of all, the user thinks that he / she gets a relatively quick relaxation because of the provision of the present invention, and secondly, the mere maintenance of nicotine in the blood is dynamic rather than a static process. Therefore, mere continuous maintenance of nicotine becomes less desirable for the user compared to the rapid relief of the cravings that have begun. In other words, alleviating craving is considered a dynamic process.

  In one embodiment of the invention, the migration rate threshold is evaluated at a partial time of about 0.5 minutes to about 2.5 minutes from the start of the chewing process.

  According to one embodiment of the present invention, a partial time of 30 seconds may be advantageous for the purpose of checking whether the mobility rate is maintained. Thus, it has been found that the migration rate measured in 30 seconds is sufficient for the purpose of obtaining rapid relaxation. Thus, if a partial time of 30 seconds is applied, the movement takes four partial times: 0.5 to 1 minute, 1 to 1.5 minutes, 1.5 to 2 minutes, 2 to 2 Must meet the requirements specified in a partial time of 5 minutes.

  The rate of movement may even be measured in a clearly shorter partial time, for example 15 seconds may be applied. A longer partial time, or a different length of partial time, may be applied, but this time is intended to avoid a drop or dropout of nicotine or tobacco alkaloid migration during its intermediate release, You must choose carefully. In particular, according to the present invention, a dropout in the middle, i.e. about 0.5 to 2.5 minutes of movement, is inevitably required in spite of the fact that the overall nicotine release is high. It will give you reduced movement and must be avoided.

  In one embodiment of the invention, the chewing gum is chewed for a time of about 2.5 minutes to about 10 minutes from the start of the chewing process, preferably from about 2.5 minutes to about 5 minutes from the start of the chewing process. In time, it includes a chewing process that involves the movement of tobacco alkaloids from the chewing gum with a migration rate that exceeds a further migration rate threshold.

According to another embodiment of the invention, an additional threshold may be applied to the chewing process after the first 2.5 minutes of chewing. Thus, according to an advantageous embodiment of the present invention, such a threshold is preferably obtained for a relatively high tobacco alkaloid movement in a time of 2.5 to 10 minutes, preferably at least 5 minutes. We must ensure that.
In this way, the initially obtained relaxation is maintained.

  In one embodiment of the present invention, the movement rate threshold is included in the chewing gum before chewing every 30 seconds from about 0.5 minutes to about 2.5 minutes from the start of the chewing process. Produces a release of at least 2%, preferably at least 2.5% of the tobacco alkaloids present.

  According to one embodiment of the present invention, the release of tobacco alkaloid by chewing is at least 2%, preferably at least 2.5% every 30 seconds, thereby maintaining a high osmotic pressure on the mucosa when chewing . The emphasis on keeping tobacco alkaloids available continuously in the mouth at this early stage should preferably have a quick relaxation for the user much faster compared to conventional tobacco alkaloid-containing chewing gums, And such desirable rapid relief is high in tobacco alkaloids in the mouth, which is not only sporadically or late in the release phase, but is normally maintained for at least a portion of the time required to smoke a single cigarette. It is particularly important early in the mastication process because of the need for availability.

  In one embodiment of the present invention, the movement rate threshold is included in the chewing gum before chewing every 30 seconds from about 0.5 minutes to about 2.5 minutes from the start of the chewing process. Result in a release of at least 3%, preferably at least about 4% of the tobacco alkaloids present.

  In one embodiment of the invention, chewing tobacco alkaloid release is at least 3%, preferably at least 4% every 30 seconds, thereby maintaining high osmotic pressure on the mucosa when chewing. The emphasis on keeping tobacco alkaloids constantly available in the mouth at this early stage should preferably obtain rapid relief for the user much faster compared to conventional tobacco alkaloid-containing chewing gums, and Such desirable rapid mitigation increases the high availability of tobacco alkaloids in the mouth for at least a portion of the time normally required to smoke a single cigarette, not just sporadic or late release phases. It is particularly important in the early stages of chewing because of the fact that it needs to be maintained constantly.

  In one embodiment of the present invention, the movement rate threshold is included in the chewing gum before chewing every 30 seconds from about 0.5 minutes to about 2.5 minutes from the start of the chewing process. Produces a release of at least 5%, preferably at least about 6% of the tobacco alkaloids present.

  According to a further advantageous embodiment of the invention, the mobility can be achieved and maintained at a high level, thereby featuring an improved quick relaxation of the user.

  In one embodiment of the present invention, the migration rate threshold is about 2.5 to about 5 minutes from the start of the chewing process, every 30 seconds, and the tobacco contained in the chewing gum before chewing It produces a release of at least 2%, preferably at least 3% of the alkaloid.

  According to a further advantageous embodiment of the invention, the tobacco alkaloid must also remain available at a high rate for a time of about 2.5 to 5 minutes after the start of the chewing process. Again, it should be noted that such threshold speeds must be met virtually always within an interval of 2.5 to 5 minutes from the start of the chewing process.

  In one embodiment of the present invention, the migration rate threshold is about 2.5 to about 5 minutes from the start of the chewing process, every 30 seconds, and the tobacco contained in the chewing gum before chewing It produces a release of at least 3%, preferably at least 3.5% of the alkaloid.

  According to a further advantageous embodiment of the invention, the tobacco alkaloid must also remain available at a high rate for a period of about 2.5 to 5 minutes after the start of the chewing process. Again, it should be noted that such a threshold speed must be accommodated virtually always within an interval of 2.5 to 5 minutes from the start of the chewing process.

  In one embodiment of the present invention, the migration rate threshold is set to about 5 to 10 minutes from the start of the chewing process, every 30 seconds, and the tobacco alkaloid contained in the chewing gum before chewing. It produces a release of at least 4%, preferably at least 5%.

  In one embodiment of the invention, the migration rate threshold is at least 2 to 10 of the tobacco alkaloids contained in the chewing gum prior to chewing during a time period of about 0 to about 30 seconds from the start of the chewing process. %, Preferably at least 5% release.

  In one embodiment of the invention, the migration rate threshold is less than 14% of the tobacco alkaloids contained in the chewing gum prior to chewing during a time of about 0 seconds to 2.5 minutes from the start of the chewing process. Preferably giving less than 12% release.

  According to one embodiment of the present invention, the initial movement of tobacco alkaloids from the chewing gum is 12 to 14% of the tobacco alkaloids contained in the chewing gum before chewing to avoid so-called tingling or tingling sensations. Must be kept below. Furthermore, too much release of nicotine, for example, also results in a portion of the released nicotine being swallowed and thus only effective by metabolic transfer.

  In one embodiment of the invention, the migration rate threshold is a maximum of 18% of the tobacco alkaloids contained in the chewing gum before chewing during a time of about 10 to about 30 minutes from the start of the chewing process, Preferably, a maximum of 15% release occurs.

  In one embodiment of the invention, the mobility threshold is included in the chewing gum before chewing every 30 seconds, from about 0.5 to about 2.5 minutes from the start of the chewing process. Produces a release of at least 0.03 mg, preferably at least 0.04 mg of tobacco alkaloids.

  According to the present invention, the accumulation of nicotine or tobacco alkaloids in the blood must be obtained by a sustained osmotic pressure on the oral mucosa, preferably in the intermediate time of the chewing process, for example in the first 10 minutes of the chewing process .

  In one embodiment of the present invention, the movement rate threshold is included in the chewing gum before chewing every 30 seconds from about 0.5 minutes to about 2.5 minutes from the start of the chewing process. Produces a release of at least 0.05 mg, preferably at least 0.06 mg, of tobacco alkaloids.

  In one embodiment of the present invention, the movement rate threshold is included in the chewing gum before chewing every 30 seconds from about 0.5 minutes to about 2.5 minutes from the start of the chewing process. Produces a release of at least 0.08 mg, preferably at least 0.1 mg, of tobacco alkaloids.

  In one embodiment of the present invention, the migration rate threshold is about 2.5 to about 5 minutes from the start of the chewing process, every 30 seconds, and the tobacco contained in the chewing gum before chewing This produces a release of at least 0.03 mg, preferably at least 0.04 mg of alkaloid.

  In one embodiment of the present invention, the migration rate threshold is about 2.5 to about 5 minutes from the start of the chewing process, every 30 seconds, and the tobacco contained in the chewing gum before chewing This produces a release of at least 0.05 mg, preferably at least 0.06 mg of alkaloid.

  In one embodiment of the present invention, the migration rate threshold is included in the chewing gum before chewing every 30 seconds from about 2.5 minutes to about 5 minutes from the start of the chewing process. This produces a release of at least 0.08 mg, preferably at least 0.1 mg of alkaloid.

  In one embodiment of the invention, at least 0.5 mg of tobacco alkaloid is released within the first 10 minutes of the chewing process, preferably within the first 5 to 8 minutes of the chewing process.

  According to one embodiment of the present invention, even higher release must be obtained, for example at least 0 of tobacco alkaloids within the first 10 minutes of the chewing process, preferably within the first 5 to 8 minutes of the chewing process. .8 mg is released.

  In one embodiment of the invention, different parts of the chewing gum are intended for the movement of tobacco alkaloids at different times during the chewing process or during different times.

  According to one embodiment of the present invention, different parts of the chewing gum can be aimed at the movement of tobacco alkaloids at different points in time of chewing or during different times, which makes it suitable for the appropriate time of the chewing process, i.e. usually Facilitates obtaining the desired constant movement or at least the desired minimum movement during the first 3 to 5 minutes of the chewing process. Thus, for example, the very early movement of tobacco alkaloids, ie the first few seconds of the chewing process, can be increased, for example by means of a nicotine-containing coating. Alternatively, nicotine can be included in beads or other release delaying means. In addition, other means may include a mixture of different polymers having different release properties. Other means may include various types of buffers.

  Thus, the migration rate threshold is obtained by a combination of different portions of chewing gum having different release profiles.

  In one embodiment of the invention, the chewing gum includes a coating, and the coating includes a tobacco alkaloid.

  In one embodiment of the present invention, tobacco alkaloids are included in the coating so that they can be released fairly quickly during the very early stages of the chewing process.

In one embodiment of the invention, the chewing gum comprises a substantially hydrophilic polymer.
In one embodiment of the present invention, the variation in mobility is minimized.

  According to one embodiment of the present invention, significant variations in tobacco alkaloids over time must be avoided in order to obtain an advantageous masking of taste. Thus, sudden tobacco alkaloid peaks are difficult for taste masking, especially when dealing with peaks that occur very early in the chewing process. I1 and I3 below are examples of such flattened emissions.

In one embodiment of the present invention, the tobacco alkaloid is contained in an ion exchange resin.
According to one embodiment, the tobacco alkaloid is nicotine polacrilex.

In one embodiment of the invention, the tobacco alkaloid comprises a salt of nicotine.
In one embodiment of the invention, the tobacco alkaloid comprises free form nicotine.

In one embodiment of the invention, the tobacco alkaloid is buffered.
In one embodiment of the invention, the chewing process is less than 30 minutes, preferably less than 20 minutes.

According to one embodiment, the chewing process must be kept short in order to adapt to the basic principles of rapid relaxation obtained by mimicking the desired smoking process.
In one embodiment of the invention, the mastication process corresponds to the smoking time of one cigarette.

  In one embodiment of the present invention, the chewing gum comprises from about 2 to about 99% by weight of the polymer system, from about 0.001 to about 30% by weight of the flavoring agent, and from about 2 to about 80% by weight of the sweetener. % Amount included.

  In one embodiment of the invention, the chewing gum comprises from about 0 to about 60% by weight filler, from about 0.001 to about 30% by weight flavor and from about 2 to about 80% sweetener. % Amount included.

  In one embodiment of the invention, the chewing gum includes a strong sweetener in an amount of about 0.001 to about 3% by weight and a flavoring agent in an amount of about 0.001 to about 30% by weight.

  In one embodiment of the invention, the polymer system comprises an elastomer in an amount of about 0.1 to about 40% by weight of the chewing gum, preferably about 2 to about 10% by weight of the chewing gum.

  In one embodiment of the invention, the polymer system comprises an elastomer plasticizer in an amount from about 2 to about 60% by weight of the chewing gum, preferably from about 5 to about 30% by weight of the chewing gum.

  In one embodiment of the invention, the polymer system comprises wax in an amount of about 0 to about 30% by weight of the chewing gum, preferably about 0 to about 15% by weight of the chewing gum.

  In one embodiment of the invention, the polymer system comprises a softening agent in an amount of about 2 to about 30% by weight of the chewing gum, preferably in an amount of about 5 to about 20% by weight of the chewing gum.

  In one embodiment of the invention, the polymer system comprises a filler in an amount from about 0 to about 50% by weight of the chewing gum, preferably from about 0 to about 30% by weight of the chewing gum.

  In one embodiment of the invention, the polymer system comprises an antioxidant in an amount of about 0 to about 5% by weight of the chewing gum, preferably in an amount of about 0 to about 2% by weight of the chewing gum.

  In one embodiment of the invention, at least one chewing gum is chewed at a time.

  In one embodiment of the invention, at least two chewing gums are chewed at a time.

  In one embodiment of the invention, at least one chewing gum is chewed per day.

  In one embodiment of the invention, at least one chewing gum is chewed when the person is craving for nicotine.

  According to an advantageous embodiment of the invention, the chewing gum holding tobacco alkaloids can be applied only in response to the user's cravings. In other words, it is possible to avoid simply maintaining high nicotine levels in the blood.

In one embodiment of the invention, at least one of the chewing gums is chewed when the person is in need of treatment containing tobacco alkaloids or nicotine.
The present invention will now be described with reference to the drawings.

It is a graph which shows the mode of discharge | release of the nicotine chewing gum of a prior art. 2 is a graph showing the mid-term release of prior art nicotine chewing gum divided into 30 second intervals. 3 is a graph showing the mid-term release of nicotine chewing gum applied according to the present invention divided into 30 second intervals. 2 is a graph showing the release of a combination of a prior art chewing gum and a chewing gum according to the present invention.

  In general, chewing gum compositions usually comprise a majority of a water soluble, water insoluble chewable gum base portion and a flavoring agent. The water soluble part will dissipate over the time of chewing along with the flavoring part. The gum base portion is held in the mouth throughout chewing. The term chewing gum refers to both types of gum, chewing gum and fusen gum, in a general sense.

  The gum base is a chewing gum chew and imparts chewing properties to the final product. Gum base usually determines the release of flavors and sweeteners and plays an important role in gum products.

  The insoluble part of the gum may typically contain any combination of elastomers, vinyl polymers, elastomer plasticizers, waxes, softeners, fillers and other optional ingredients such as colorants and antioxidants.

  The composition of the gum base formulation can vary greatly depending on the particular product to be prepared and the desired chewing and other perceptual characteristics of the final product. However, the usual ranges of said gum base components (in weight percent) are 5 to 50% by weight elastomer compound, 5 to 55% by weight elastomer plasticizer, 0 to 40% by weight wax, 5 to 35% by weight softener, 0 to 50% by weight of filler and 0 to 5% by weight of other components such as antioxidants, colorants.

Elastomer Function Elastomers impart gum-like tackiness to gums that varies depending on the chemical structure of this component and how it is compounded with other components. Suitable elastomers for use in gum bases and gums of the present invention include natural or synthetic types.

Elastomers Elastomers can be any water-insoluble polymer known in the art, and are listed as “Mustatory Substitutes of Natural Vegetable Origins and the Strains” in Food and Drug Administration, CFR, Title 21, Section 172615. Gum polymers used in chewing gum and fussen gum that have been used.

  Useful natural elastomers include natural rubbers such as smoked or liquid latex and guayule rubber, such as gelton, lechi caspi, perillo, sorva, massalanduba balata, massaland bacho colata (Massaradanba chocolate), nispero, rosidinha, chicle, gutta percha, gutta kataiu, niger gutta, tunu, chiruburu, gutta gang

  Useful synthetic elastomers include high molecular weight elastomers such as butadiene-styrene copolymers, polyisobutadiene and isobutylene-isoprene copolymers, low molecular weight elastomers such as polybutene, polybutadiene and polyisobutylene, vinyl polymer based elastomers such as polyvinyl acetate, polyethylene, Vinyl acetate / vinyl laurate, vinyl acetate / vinyl stearate, vinyl copolymer elastomers such as ethylene / vinyl acetate, polyvinyl alcohol, or mixtures thereof.

  Butadiene-styrene type elastomers, sometimes referred to as SBR, are usually copolymers of styrene: butadiene from about 20:80 to 60:40 monomers. The ratio of these monomers affects the elasticity of SBR as assessed by Mooney viscosity. The Mooney viscosity decreases as the styrene: butadiene ratio decreases. The structure of SBR usually consists of linear 1,3-butadiene copolymerized with phenylethylene (styrene), giving the non-linear molecular properties of these elastomers. The average molecular weight of SBR is less than 600,000 g / mol.

  The isobutylene-isoprene type elastomer, sometimes referred to as butyl, has a level of isoprene in the range of 0.2 to 4.0 mole percent. Similar to SBR, as the isoprene: isobutylene ratio decreases, so does the elasticity measured by Mooney viscosity.

  The structure of butyl rubber usually consists of branched 2-methyl-1,3-butadiene (isoprene) copolymerized with branched 2-methylpropene (isobutylene), and this type of structure is essentially non-linear, as in SBR. It is. The average molecular weight of SBR ranges from 150,000 g / mol to 1,000,000 g / mol.

  Polyisobutylene is sometimes referred to as PIB, and this type of elastomer is a polymer of 2-methylpropene and is inherently non-linear, as is the case with SBR and butyl. Low molecular weight elastomers give the gum base a soft chewing feel and still give it an elastic character like other elastomers. The average molecular weight may be in the range of 30,000 to 120,000 g / mol and the penetration may be in the range of about 4 millimeters to 20 millimeters. The greater the penetration, the softer the PIB. Similar to SBR and butyl, high molecular weight elastomers give the gum elasticity. The average molecular weight may be in the range of 120,000 to 1,000,000 g / mol.

  Polybutene has an average molecular weight in the range of about 5,000 g / mol to about 30,000 g / mol.

Functionality of vinyl polymers Vinyl polymers and vinyl copolymer elastomers provide adhesion resistance, change the chewing feeling of gums made from substrates with these vinyl polymers, and provide hydrophilic properties that are beneficial to the sensory perception of the final gum. provide.

Vinyl polymers For vinyl copolymer types, vinyl laurate / vinyl acetate (VL / VA), vinyl stearate / vinyl acetate (VS / VA), or vinyl laurate present in ethylene / vinyl acetate (EVA) copolymers, acetic acid The amount of vinyl or ethylene usually ranges from about 10 to about 60% by weight of the copolymer. The average molecular weight of these polymers may be in the range of about 2,000 g / mol to about 100,000 g / mol.

  Vinyl polymers such as polyvinyl alcohol and polyvinyl acetate have an average molecular weight of about 8,000 to 65,000 g / mol. Vinyl acetate polymer (PVAc) is inherently branched. The degree of branching increases when the vinyl acetate monomer is copolymerized with vinyl laurate, vinyl stearate, ethylene and the like. The greater the degree of branching, the greater the compatibility when blended or blended with normal-alkane and iso-alkane type waxes.

  For example, it is common in the art to combine a high molecular weight synthetic elastomer and a low molecular weight elastomer in a gum base. Presently preferred synthetic elastomer combinations include polyisobutylene and styrene butadiene, polyisobutylene and polyisoprene, polyisobutylene and isobutylene-isoprene copolymer (butyl rubber) and polyisobutylene, styrene-butadiene copolymer and isobutylene isoprene copolymer, and Examples include, but are not limited to, mixtures of all individual synthetic polymers with polyvinyl acetate, each of vinyl acetate vinyl laurate copolymers, and mixtures thereof.

Function of Elastomer Plasticizer Elastomer plasticizer changes the texture of the gum base. These specificities with respect to intermolecular chain breakage (plasticization) of elastomers, together with their various softening points, are responsible for the various chewy and compatible textures of the resulting gum when used in a gum base. This is important when it is desired to expose more of the alkane chains of the wax to the elastomeric chains.

Elastomeric Plasticizers Elastomeric plasticizers suitable for use in the present invention include natural rosin, a natural rosin ester often referred to as ester gum. Such elastomer plasticizers known in the art are methyl, glycerin and pentaerythritol esters of rosins and modified rosins such as hydrogenated, dimerized and polymerized rosins. Examples are glycerin esters of wood rosin and gum rosin, glycerin esters of partially hydrogenated wood rosin and gum rosin, glycerin ester of polymerized wood rosin and gum rosin, glycerin ester of partially dimerized wood rosin and gum rosin, glycerin ester of tall oil rosin, wood rosin and gum rosin Pentaerythritol esters, partially and fully hydrogenated wood rosins and gum rosin pentaerythritol esters, wood rosin and gum rosin methyl esters, partially and fully hydrogenated wood rosins and gum rosin methyl esters.

  Synthetic elastomer plasticizers include terpene resins derived from α-pinene, β-pinene and / or d-limonene.

  The elastomer plasticizer used may be one type or a combination of two or more types. Usually, the ratio of one to the other depends on the softening point of each individual, their respective effects on flavor release, and the respective degree of stickiness they impart to the gum. The rosin ester type ring and ball softening point may range from about 45 ° C to about 120 ° C. The softening point of the terpene resin may range from about 60 ° C to about 130 ° C.

The function of the wax Petroleum wax helps cure the finished gum made from the gum base and also improves the shelf life and texture. The size of the wax crystals affects the release of flavor. High isoalkane waxes have a smaller crystal size than high normal alkanes, especially those having less than 30 carbon atoms. The small crystal size allows for a slower flavor release than waxes with a large crystal size, as there is a greater hindrance to flavor dissipation from this wax. The compatibility of gum bases made with normal alkane waxes is low compared to gum bases made with isoalkane waxes.

Wax Petroleum waxes (refined paraffin and microcrystalline waxes) and paraffin waxes are mainly composed of linear normal alkanes and branched isoalkanes. The ratio of normal alkanes to isoalkanes varies.

  Normal alkane waxes usually have a carbon chain length of> C18, but lengths longer than C-30 are not overwhelming. Branches and ring structures are located near the ends of these wax chains, which are predominantly normal alkanes. The viscosity of the normal alkane wax is <10 mm 2 / s (at 100 ° C.) and the combined number average molecular weight is <600 g / mol.

  Isoalkane waxes usually have a carbon length that is largely greater than C30. Branched chains and ring structures are randomly located along the carbon chains in these waxes that are predominantly isoalkanes. The viscosity of the isoalkane wax exceeds 10 mm 2 / s (at 100 ° C.) and the combined number average molecular weight is> 600 g / mol.

  Synthetic waxes are produced by means that are unusual for the production of petroleum waxes and are therefore not considered petroleum waxes. Synthetic waxes include those containing branched alkanes and may be copolymerized with monomers such as, but not limited to, propylene, polyethylene, and Fischer-Tropsch wax. Polyethylene wax is a synthetic wax containing alkane units of various lengths, to which ethylene monomer is bonded.

Natural waxes can include rice bran wax, beeswax, carnauba wax, or candelilla wax.
The waxes can be used alone or in any combination.

Softener function The choice of softener affects the softness of the base. Softeners may modify the texture, make the base hydrophobic and hydrophilic components miscible, and also plasticize the gum-based synthetic elastomer. Emulsifiers belonging to the group of softeners provide the gum base with water binding properties that give the gum base a pleasant smooth surface and reduce stickiness.

Softening agents Softening agents suitable for use in gum bases include emulsifiers in addition to triglycerides in non-hydrogenated, partially hydrogenated and fully hydrogenated vegetable oils and tallow, cocoa butter and degreased cocoa powder. .

  The triglyceride group includes cottonseed, palm, palm kernel, coconut, safflower, rapeseed, sunflower, tallow, soybean, cacao butter, medium chain triglyceride and the like.

  The triglycerides capron, capryl, caprin, myristic, laurin, and palmitic fatty acids plasticize synthetic elastomers over triglycerides that contain predominantly stearic fatty acids.

  The group of emulsifiers includes monoglycerides, diglycerides, acetylated mono and di glycerides, distilled mono and di glycerides, glycerin monostearate, propylene glycol monostearate, stearic acid Na, K, Mg and Ca, glycerin triacetate, fatty acid monoglycerides (eg stearin, palmitic, olein, and linoleic acid), lactic and acetate esters of mono and diglycerides, also called sucrose polyesters, disclosed in WO 00/25598 Sugar esters of edible fatty acids, including lecithins and hydroxylated lecithins, most of which may contain triglycerides from their processing at levels of less than 2% by weight. .

  The softening agent containing an emulsifier can be used alone or in combination of two or more.

Filler Function Fillers used in the gum base modify the texture of the gum base and aid in processing. Particle size has an impact on the cohesiveness, density, processing characteristics and formulation of the gum base. The smaller the particle size, the denser and more cohesive the final gum base. Also, by selecting the filler based on its particle size distribution, the initial mass formulation can be altered, thus the initial mass formulation characteristics during gum base processing and the gums ultimately made from these gum bases. It becomes possible to change the biting comfort of the finish.

Fillers suitable for use in gum base include magnesium carbonate and calcium carbonate, powdered limestone and silicates such as magnesium silicate and aluminum silicate, kaolin and clay, aluminum oxide, silicon oxide, talc, As well as titanium oxide, mono, di and tri calcium salts of phosphoric acid, cellulose polymers such as sodium sulfate, ethyl, methyl and wood or mixtures thereof.

  Talc fillers may provide the necessary acidic environment to prevent degradation of artificial sweeteners by contact with or using acid flavors or by reacting with calcium carbonate fillers It can be used in the gum bases and gums of the present invention. The average particle size of calcium carbonate and talc filler is usually in the range of about 0.1 microns to about 15 microns.

Fillers may also include natural organic fibers such as fruit plant fibers, cereals, rice, cellulose and combinations thereof.
Function and list of other optional ingredients such as antioxidants, colorants and flavors:

  Antioxidants prolong shelf life and storage of individual ingredients including gum bases, finished gums or their fat and flavor oils.

  Suitable antioxidants for use in gum bases include butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), beta-carotene, tocopherol, vitamin C and other acidulants, propyl gallate, and other Synthetic and natural or mixtures thereof are included.

  Flavoring and coloring agents add features or remove or mask unwanted features. Colorants typically include FD & C lakes, plant extracts, fruit and vegetable extracts, and titanium dioxide, and flavorants typically include cocoa powder, heat-denatured amino acids, and other plant extracts.

Gum Base Preparation A gum base usually has a quantity of elastomer, elastomer plasticizers and fillers, and sometimes vinyl polymer, in a heated (10 ° C. to 120 ° C.) sigma blade mixer with a front to back speed ratio of about 1. Prepare by adding from 2: 1 to about 2: 1. This relatively high ratio is usually used for gum bases that require a relatively tight blend of elastomers.

  The initial amount of ingredients comprising the initial mass may be determined by the working capacity of the mixing can to achieve the proper homogeneity and the desired degree of blending to cut the elastomer and increase chain branching. . The higher the level at the beginning of the filler or the choice of filler with a certain particle size distribution, the higher the degree of compounding and thus more of the elastomer chain crosslinks are broken, which causes the elastomer Branching increases and the viscosity of the gum base decreases, thus softening the final gum base and the gum made from the gum base. The longer the compounding time, the lower the molecular weight or the lower the softening point, the lower the viscosity and chewy of the final gum base.

  Formulation usually begins to become effective after the ingredients are brought together into a lump. The length of the compounding time may be anywhere from 15 minutes to 90 minutes.

  Preferably, the blending time is from 20 minutes to about 60 minutes. The amount of elastomer plasticizer added depends on the level of elastomer and filler present. If too much elastomer plasticizer is added, the initial mass becomes too plastic and becomes inhomogeneous.

  After the initial ingredients are homogeneously agglomerated and blended for the desired time, the remainder of the gum base ingredients are added sequentially until a completely homogeneous molten mass is obtained. Typically, all of the rest of the elastomer, elastomer plasticizer, vinyl polymer and filler are added by 60 minutes after the start of compounding. During this time, filler and elastomer plasticizer are usually weighed separately and added in portions. Optional waxes and softeners are usually added during the next 60 minutes after the elastomer and elastomer plasticizer. Wait for the mass to become homogeneous before removing it.

Typical gum base processing times may vary from about 1 hour to about 3 hours, preferably from about 1.5 hours to 2.5 hours, depending on the formulation. The temperature of the final mass when removed may be between 70 ° C and 130 ° C, preferably between 100 ° C and 120 ° C. The finished molten mass is transferred from the mixing can to a coated or lined dish, extruded or molded into any desired shape, and allowed to cool and solidify. Those skilled in the art will recognize that many variations of the above procedure can be used.
Water-soluble part of chewing gum

  The water soluble portion of the chewing gum can include softening agents, sweeteners, high intensity sweeteners, flavoring agents, sour agents, fillers, antioxidants, and other ingredients that provide the desired attributes. Softeners usually make up from about 0.5% to 25.0% by weight of the chewing gum. The bulking agent generally comprises from about 5% to about 90%, preferably from about 20% to about 80% of the chewing gum. High intensity sweeteners in gum are usually in the range of about 0.01 to 0.50% by weight. The flavoring agent can be present in the chewing gum in an amount ranging from about 0.1 to about 30.0% by weight of the gum.

Softeners Softeners are added to the chewing gum to optimize the chewing and mouth feel of the gum.

  Softeners intended for use in gums include glycerin, modified lecithin and combinations thereof. Other aqueous sweetener solutions such as sorbitol, hydrogenated starch hydrolysate, corn syrup and combinations thereof can be used as a softening agent.

Sweeteners Most sweeteners contain both sugar and sugar-free ingredients. Most sweeteners may usually constitute from 5 to about 95% by weight of the chewing gum, more usually from 20 to about 80%, and more typically from 30 to 60% by weight of the gum.

  Sweeteners often fulfill the role of bulking agents in the cam. The sweetener improves the juiciness of the gum and also supports the flavor profile of the gum. Sugar sweeteners generally include monosaccharide-containing ingredients widely known in the chewing gum industry, such as sucrose, dextrose, maltose, saccharose, lactose, sorbose, dextrin, trehalose, D-tagatose, dry invert sugar, fructose, levulose , Galactose, corn syrup solids, glucose syrup, hydrogenated glucose syrup, and the like alone or in combination.

Sweeteners can be used in combination with sugar-free sweeteners.
In general, sugar-free sweeteners contain ingredients with sweetness characteristics, but do not contain widely known sugars, such as sorbitol, mannitol, xylitol, hydrogenated starch hydrolysates, maltitol, isomalt , Sugar alcohols such as erythritol, lactitol, alone or in combination, but are not limited to these.

  Most sweeteners can also be used in combination with high intensity sweeteners, depending on the specific sweetness release profile required and shelf stability. Preferred high intensity sweeteners include sucralose, aspartame, acesulfame salt, alitame, saccharin and its salts, cyclamic acid and its salts, cyclamate, glycyllysine, dihydrochalcone, thaumatin, monelin, sterioside, alone or in combination However, it is not limited to these. In order to provide long lasting sweetness and flavor perception, it may be desirable to encapsulate or otherwise control the release of at least some of these artificial sweeteners. Techniques such as wet granulation, wax granulation, spray drying, spray ice cooling, fluidized bed coating, coacervation, encapsulation in yeast cells, fiber extrusion, etc. can be used to achieve the desired release characteristics. is there. Encapsulation can also be performed in other materials such as resins.

  The concentration of artificial sweetener used varies greatly and depends on factors such as sweetener efficacy, release rate, desired sweetness of the product, concentration and type of flavoring agent used, and cost considerations. Therefore, the concentration of artificial sweeteners actually used can vary from 0.02 to about 8%. When the medium used for encapsulation is included, the use concentration of the encapsulated sweetener is proportionally higher.

A combination of sugar and / or sugar-free sweeteners may be used in the chewing gum.
In addition, if a softening agent such as an aqueous solution of sugar or alditol is used, this softening agent may also provide additional sweetness.

  If a low calorie gum is desired, a low calorie bulking agent can be used. Examples of low calorie bulking agents include polydextrose; Raftilose, Raftilin; Fructooligo-saccharides (NutraFlora @); Palatinose oligosaccharide; However, other low calorie bulking agents can be used.

Flavor Chewing gum cores provided herein include fragrances and flavors, including natural and synthetic flavors in the form of natural plant ingredients, essential oils, essences, extracts, powders, and the like in acid and other taste profiles. It may contain, including substances capable of affecting it. Liquid and powder flavors include coconut, coffee, chocolate, vanilla, grapefruit, orange, lime, menthol, licorice, caramel aroma, honey aroma, peanut, walnut, cashew, hazelnut, almond, pineapple, strawberry, raspberry, Includes tropical fruit, cherry, cinnamon, peppermint, wintergreen, spearmint, eucalyptus, and mint, and fruit essences such as from apple, pear, peach, strawberry, apricot, raspberry, cherry, pineapple, and plum essence. Essential oils include peppermint, spearmint, menthol, eucalyptus, clover oil, bay oil, anise, thyme, scented oil, nutmeg, and fruit oils such as those described above (eg lemon, bergamot and orange).

  The chewing gum flavor may be a lyophilized natural flavor, preferably in the form of a powder, slice or a combination thereof. The particle size may be less than 3 mm, preferably less than 2 mm, more preferably less than 1 mm, calculated as the longest dimension of the particle. Natural flavors may be in any form that has a particle size of about 3 μm to 2 mm, such as 4 μm to 1 mm. Preferred natural flavors include fruit seeds such as strawberry, blackberry and raspberry seeds.

  Various synthetic flavors such as mixed fruit flavors can also be used in the chewing gum core of the present invention. This fragrance can be used in a smaller amount than those conventionally used. This fragrance and / or flavoring is in an amount of 0.01 to about 30% by weight (preferably 0.01 to about 15% by weight) of the final product, depending on the desired strength of the fragrance or flavoring used. Can be used. Preferably, the fragrance / flavoring content is in the range of 0.2 to 3% by weight of the total composition.

Acids A variety of acids such as adipic acid, succinic acid, fumaric acid, citric acid, tartaric acid, malic acid, acetic acid, lactic acid, phosphoric acid, glutaric acid and their salts are also commonly used in combination with fruit flavors. The These are usually added in an amount of 0.01 to 10%.

Fillers suitable for use in chewing gum include magnesium carbonate and calcium carbonate, powdered limestone and silicates such as magnesium silicate and aluminum silicate, kaolin and clay, aluminum oxide, silicon oxide, talc, As well as titanium oxide, mono, di and tri calcium salts of phosphoric acid, cellulose polymers such as sodium sulfate, ethyl, methyl and wood or mixtures thereof.

  Talc fillers may provide the acidic environment necessary to contact acid flavors, use acid flavors, or prevent degradation of artificial sweeteners by reacting with calcium carbonate type fillers Can be used in the present chewing gum. The average particle size of calcium carbonate and talc filler is usually in the range of about 0.1 to 15 microns.

  Fillers may also include natural organic fibers such as fruit plant fibers, cereals, rice, cellulose and combinations thereof.

Functions and list of other optional ingredients such as antioxidants, colorants and taste masking agents. Antioxidants are shelved and stored in gum bases, finished gums or individual ingredients including these fats and flavor oils. Is extended.

Antioxidants Suitable antioxidants for use in gum bases include butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), β-carotene, tocopherol, vitamin C and other acidulants, propyl gallate , Other synthetic and natural or mixtures thereof.

Colorants Colorants and bleaching agents can typically include FD & C type dye lakes, fruit and vegetable extracts and titanium dioxide, and combinations thereof.

Taste masking agent Taste masking agent improves the sensory stimulation of the product. Masking agents include sucralose, zinc gluconate, ethyl maltol, glycine, acesulfame K, aspartame, saccharin, fructose, xylitol, spray dried licorice root, glycerritine, dextrose, sodium gluconate, glucono delta lactone, ethyl vanillin , Vanillin, normal or high intensity sweeteners, and various suitable flavors.

Active ingredient The chewing gum according to the present invention may also contain an active ingredient other than nicotine. The active ingredient used in the context of the present invention can be any substance that is desired to be released from the chewing gum. If an accelerated release rate is desired, corresponding to the effect obtained with respect to the flavor, the main substances usually have a limited water solubility of less than 10 g / 100 mL, including totally water-insoluble substances. Is. Examples are drugs, dietary supplements, oral compositions, smoking cessation agents, high intensity sweeteners, pH adjusters and the like.

  Other examples of active ingredients include paracetamol, benzocaine, cinnarizine, menthol, carvone, caffeine, chlorhexidine diacetate, cyclidine hydrochloride, 1,8-cineole, nandrolone, miconazole, mystatin, aspartame, sodium fluoride, nicotine, Active ingredients of saccharin, cetylpyridinium chloride, other quaternary ammonium compounds, vitamin E, vitamin A, vitamin D, glibenclamide or derivatives thereof, progesterone, acetylsalicylic acid, dimenhydrinate, cyclidine, metronidazole, sodium bicarbonate, ginkgo , Propolis active ingredient, ginseng active ingredient, methadone, peppermint oil, salicylamide, hydrocortisone, astemizole.

  Examples of active ingredients in the form of dietary supplements are, for example, vitamin B2 (riboflavin), B12, folic acid, niacin, biotin, poorly soluble glycerophosphoric acid, amino acids, vitamins A, D, E and K having a nutritional effect And compounds, salts and minerals, calcium, phosphorus, magnesium, iron, zinc, copper, iodine, manganese, chromium, selenium, molybdenum, potassium, sodium or cobalt complexes and compounds.

  In addition, reference is made to a list of nutrients approved by various national authorities, eg, US Code Vol. 21, 182: 5013, 182: 5997, and 182: 8013-182: 8997.

  Examples of active ingredients in the form of compounds for oral and dental care or treatment are, for example, constrained hydrogen peroxide and compounds capable of releasing urea during chewing.

  Examples of active ingredients in the form of preservatives are, for example, guanidine and bidiguanidine salts and compounds (for example chlorhexidine diacetate) and also have the following types of substances with limited water solubility: quaternary ammonium compounds (for example Ceramine, chloroxylenol, crystal violet, chloramine), aldehyde (eg paraformaldehyde), decalin compound, polynoxyline, phenols (eg thymol, parachlorophenol, cresol), hexachlorophene, salicylic acid anilide compound, triclosan, halogen (iodine) , Iodophor, chloroamine, dichlorocyanurate), alcohols (3,4-dichlorobenzyl alcohol, benzyl alcohol, phenoxyethanol, phenylethanol) See, further, Martindale, The Extra Pharmacopoeia, 28th edition, pages 547-578; metal salts, limited water-soluble complexes and compounds such as aluminum salts (eg aluminum potassium sulfate AIK (S04) 2, 12H2O) ), Boron salts, complexes and compounds, barium, strontium, iron, calcium, zinc, (zinc acetate, zinc chloride, zinc gluconate), copper (copper chloride, copper sulfate), lead, silver, magnesium, sodium, Potassium, lithium, molybdenum, vanadium must be included; other compositions for mouth and tooth care include, for example; fluorine-containing salts, complexes and compounds (sodium fluoride, monofluorolin Acid sodium, amino fluoride, fluoride ), Phosphates, carbonates and selenium.

  Furthermore, J. et al. Dent. Res. 28, 2, 160-171, 1949, refers to a wide range of test compounds, see.

  Examples of active ingredients in the form of oral pH regulators include, for example, acceptable acids such as adipic acid, succinic acid, fumaric acid or salts thereof, or citric acid, tartaric acid, malic acid, acetic acid, lactic acid, Includes salts of phosphoric acid and glutaric acid and acceptable bases such as carboxylates, bicarbonates, phosphates, sulfates or sodium, potassium, ammonium, magnesium or calcium, especially magnesium or calcium oxide .

Examples of active ingredients in the form of smoking cessation agents include, for example, nicotine, powdered tobacco or silver salts such as silver acetate, silver carbonate and silver nitrate.
Other examples of active ingredients are any type of drug.

  Examples of active ingredients in the form of drugs include caffeine, salicylic acid, salicylamide and related substances (acetylsalicylic acid, choline salicylate, magnesium salicylate, sodium salicylate), paracetamol, pentazocine salts (pentazosin hydrochloride and pentazocine lactate), buprenorphine hydrochloride, Codeine hydrochloride and codeine phosphate, morphine and morphine salts (hydrochloride, sulfate, tartrate), methadone hydrochloride, ketobemidone and salt of ketobemidone (hydrochloride), beta blocker, (propranolol), calcium antagonist, verapamil hydrochloride, nifedinpine And Pharm. Int. Nov. 85, 267-271, Barney H. et al. Hunter and Robert L. Suitable substances mentioned in Talbert and their salts, nitroglycerin, erythrityl tetranitrate, strychnine and its salts, lidocaine, tetracaine hydrochloride, etorphine hydrochloride, atropine, insulin, enzymes (eg papain, trypsin, amyloglucosidase, glucose Oxidase, streptokinase, streptodolase, dextranase, α-amylase), polypeptide (oxytocin, gonadorelin, (LH, RH), desmopressin acetate (DDAVP), isoxysprin hydrochloride, ergotamine compound, chloroquine (phosphate) Salt, sulfate), isosorbide, demoxitocin, heparin.

  Other active ingredients include β-lupeol, reticen, sildenafil citrate and derivatives thereof.

  Dental products include Carbami, CPP casein phosphopeptide; chlorhexidine, chlorhexidine diacetate, chlorhexidine chloride, chlorhexidine digluconate, hexetidine, strontium chloride, potassium chloride, sodium bicarbonate, sodium carbonate, fluorine-containing components, fluoride, Sodium fluoride, aluminum fluoride, ammonium fluoride, calcium fluoride, tin fluoride, other fluorine-containing components, ammonium fluorosilicate, potassium fluorosilicate, sodium fluorosilicate, ammonium monofluorophosphate, calcium monofluorophosphate , Potassium monofluorophosphate, sodium monofluorophosphate, octadecentyl ammonium fluoride, stearyl trihydroxyethyl propylenediamine dihydrochloride Lido include, Vitamin, A, B1, B2, B6, B12, folinic acid, niacin, Pantothensyre, biotin, C, D, E, includes K is.

  Minerals include calcium, phosphorus, magnesium, iron, zinc, copper, iodine, manganese, chromium, selenium and molybdenum. Other active ingredients include natural drugs such as Q10 @, enzymes, ginkgo biloba, ginger, fish oil. The present invention relates to migraine drugs such as serotonin antagonists; headache drugs such as sumatriptan, zolmitriptan, naratriptan, rizatriptan, eletriptan; antiemetic drugs such as cyclidine, cinnarizine, dimenhydramine, defenhydrinato; It also relates to the use of pollen fever drugs such as cetridine, loratidine, analgesics such as buprenorphine, tramadol, oral disease drugs such as miconazole, amphotericin B, triamcinolone acetone; and the drugs cisapride, domperidone, metoclopramide.

Chewing gum preparation In general, chewing gum can be produced by sequentially adding the various chewing gum ingredients into commercially available mixers known in the art. After the original ingredients are thoroughly mixed, the gum mass is removed from the mixer and rolled into sheets and then cut into sticks, extruded and chopped, or molded into pellets To form the desired shape.

  In general, the ingredients can be mixed by first melting the gum base and then adding it to a running mixer. Colorants, active ingredients and / or emulsifiers may be added simultaneously. A softening agent such as glycerin may also be added at this time along with a portion of the syrup and bulking agent / sweetener. The other part of the bulking agent / sweetener can then be added to the mixer. The flavoring agent is usually added with the last part of the bulking agent / sweetener. The high intensity sweetener is preferably added after the last part of the bulking agent and the flavoring agent have been added.

  The entire mixing procedure usually takes 5 to 15 minutes, but sometimes longer mixing times may be required. Those skilled in the art will recognize that many variations of the above procedure can be used. Among these are the one-step methods described in US Patent Application No. 2004/0115305, which is incorporated herein by reference.

Chewing Gum Structure According to the present invention, the form and shape of the nicotine chewing gum may be any suitable and user friendly structure. Thus, the gum center or gum may be in a form selected from, for example, pellets, cushion-type pellets, sticks, tablets, chopped, troches, pills, balls and spheres. Chewing gum is formed by extrusion, compression, and roll, and in any form the center may be filled with liquid and / or solid.

Coating According to the present invention, the chewing gum element may comprise from about 0.1 to about 75% by weight of an outer coating applied on the chewing gum center. Thus, suitable coating types include any composition of hard coatings, film coatings and soft coatings, including those currently used for coating chewing gums, pharmaceutical products and confectionery and any combination thereof.

  The presently preferred outer coating type is a hard coating, and the term is used in its ordinary sense of the term including sugar coatings and sugar-free (ie, sugar-free) coatings and combinations thereof. The purpose of the hard coating is to obtain a sweet and crunchy layer that is appreciated by consumers, which can also protect the gum center for a variety of reasons. In the usual method of providing a protective sugar coating on the chewing gum core, the gum center is continuously treated with an aqueous solution of a crystallizable sugar such as sucrose or dextrose in a suitable coating apparatus. This aqueous solution of sugar may contain other functional components such as fillers, binders, colorants, etc., depending on the stage of the coating. In the case of the present invention, the sugar coating may contain other functional or active compounds, including flavoring compounds and / or pharmaceutically effective compounds.

  However, in the manufacture of chewing gum, it may be preferable to replace the carious sugar compound in the coating with another, preferably crystalline, sweet compound that does not have caries action. In the art, such coatings are generally referred to as sugar-free or sugar-free coatings. Currently preferred non-cariogenic hard coating materials include polyols such as sorbitol, maltitol, mannitol, xylitol, erythritol, lactitol, isomalt and tagatose (these are industrial methods, respectively D-glucose, maltose, fructose or Levulose, xylose, erythrose, lactose, isomaltulose, isomaltose and D-galactose obtained by hydrogenation), and trehalose, a non-cariogenic mono-di-saccharide.

  In the usual hard coating process described in detail below, a suspension containing crystallizable sugar and / or polyol is applied onto the gum center and the water contained is evaporated off by blowing air. To do. This cycle must be repeated several times (usually 3 to 80 times) to reach the required expansion. The term “expansion” refers to an increase in the weight or thickness of the product (relative to the final weight or thickness of the coated product considered) compared to the beginning at the end of the coating operation. In accordance with the present invention, the coating layer comprises about 0.1 to about 75% by weight of the finished chewing gum element, for example about 10 to about 60% by weight, including about 15 to about 50% by weight.

  In other useful embodiments, the outer coating of the chewing gum element of the present invention is an element that has undergone a thin film coating process, and therefore one or more thin film forming polymeric agents and optionally one or more auxiliary compounds, such as Contains plasticizers, pigments and opacifiers. A thin film coating is a thin coating based on a polymer applied to the center of any chewing gum of the form described above. The thickness of such a coating is usually between 20 and 100 μm. In general, thin film coatings are obtained by passing the chewing gum center through a spray zone with sprayed droplets of the coating material in a suitable aqueous or organic solvent medium, after which the material attached to the gum center is removed. Allow to dry before receiving the next part of the coating. This cycle is repeated until coating is complete.

  For the present invention, suitable thin film coating polymers include edible cellulose derivatives such as cellulose ethers including methylcellulose (MC), hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), and hydroxypropylmethylcellulose (HPMC). It is. Other useful thin film coatings are acrylic polymers and copolymers, such as methyl acrylate amino ester copolymers or mixtures of cellulose derivatives and acrylic polymers. A special group of thin film coating polymers, also called functional polymers, are polymers that provide modified release performance with respect to the active ingredients of the chewing gum formulation in addition to thin film formation characteristics. Such release-modifying polymers include metal acrylate ester copolymers, ethyl cellulose (EC) and enteric polymers designed to withstand the acidic gastric environment but dissolve immediately in the duodenum. The latter group of polymers includes cellulose acetate phthalate (CAP), polyvinyl acetate phthalate (PVAP), shellac, methacrylic acid copolymers, cellulose acetate trimellitic acid (CAT) and HPMC. It will be appreciated that the outer thin film coating according to the present invention may comprise any combination of the thin film coating polymers described above.

  In other embodiments, a thin film coating layer of a chewing gum element according to the present invention comprises a plasticizer that has the ability to alter the physical properties of the polymer, making it more useful in performing its function as a thin film forming material. Including. In general, the effect of a plasticizer is to make the polymer softer and easier to mold as plasticizer molecules decouple the interactions between the polymers by intercalating between the individual polymer bundles. Most plasticizers used in thin film coatings are either amorphous or have very little crystallinity. In the case of the present invention, suitable plasticizers include glycerin, propylene glycol, polyethylene glycols, such as polyols such as 200-6000 grades of these, organic esters such as phthalates, dibutyl sebacate, citrates And oil / glycerides such as thiacetin, castor oil, acetylated monoglycerides and fractionated coconut oil.

  The choice of film-forming polymer and plasticizer for the outer coating of the chewing gum element of the present invention is sufficient to achieve the best possible barrier properties of the coating with respect to water vapor and gas dissolution and diffusion through the film. Take care.

  The thin film coating of the chewing gum element may contain one or more colorants or opacifiers. In addition to providing the desired color tone, such materials may reflect light or form a barrier to water vapor and gases. Suitable colorants / milking agents include organic dyes and their lakes, inorganic colorants such as titanium oxide, and natural colorants such as β-carotene or chlorophyll.

  In addition, the thin film coating may contain one or several flavoring agents and auxiliary substances such as waxes or polydextrose, dextrins containing maltodextrin, lactose, sugar compounds such as modified starch, proteins such as gelatin or zein, plant gums And any combination thereof.

In one particular embodiment, the chewing gum core has at least one end a film former, such as cellulose derivatives, modified starch, shellac, gum arabic, dextrin, gelatin, zein, vegetable gum, synthetic polymers, and any combination thereof. And in the form of a stick with an edible thin film comprising a coating of beeswax, carnauba wax, microcrystalline wax, waxes such as paraffin wax and combinations thereof.
The following examples are given for illustrative purposes and are not intended to limit the invention.

Gum Base Preparation A gum base is prepared containing the following ingredients:
Elastomer elastomer plasticizer wax softener filler antioxidant

  The detailed formulation is shown in Table 1. It should be emphasized that several other gum base compositions can be applied within the scope of the present invention.

  The elastomer and filler are added into a mixing can equipped with mixing means such as a horizontally installed Z-shaped stirring arm. The can was preheated at about 120 ° C. for 15 minutes. The gum was softened by being shredded into small pieces by mechanical movement within the can.

Slowly add the elastomer plasticizer to the elastomer until the mixture is homogeneous. The remaining elastomer plasticizer is then added to the can and mixed for 10 to 20 minutes. Add the softening ingredients and mix for 20 to 40 minutes until the entire mixture is homogeneous.
The mixture was then discharged into a dish and allowed to cool from 120 ° C discharge temperature to room temperature.

  Chewing gum is prepared by use of the gum base of Example 1 formulated according to Table 1. Conventional mechanical mixing procedures are used with only mild heating.

  The gum base and filler are mixed in a mixing can equipped with mixing means such as a horizontally installed Z-shaped stirring arm. The can was preheated to a temperature up to about 50 ° C.

  When the contents are homogeneous, add the other ingredients according to the specified time schedule. Nicotine is added in the first half of the mixing process.

  The piece (piece) may be blended so that the nicotine per piece is 0.1 to 8 mg, preferably 2 to 4 mg. The strips evaluated contained 2 mg nicotine per strip.

  The chewing gum was coated using a hard coating. The coating can be applied, for example, according to the method disclosed in US Pat. No. 6,627,234, incorporated herein by reference.

  Chewing gum is prepared by use of the gum base of Example 1 formulated according to Table 1. Conventional mechanical mixing procedures are used with only mild heating.

  The gum base and filler are mixed in a mixing can equipped with mixing means such as a horizontally installed Z-shaped stirring arm. The can was preheated to a temperature up to about 50 ° C.

  When the contents are homogeneous, add the other ingredients according to the specified time schedule. Nicotine is added in the first half of the mixing process.

  The piece (piece) may be blended so that the nicotine per piece is 0.1 to 8 mg, preferably 2 to 4 mg. The strips evaluated contained 2 mg nicotine per strip.

  The chewing gum was coated using a hard coating. The coating can be applied, for example, according to the method disclosed in US Pat. No. 6,627,234, incorporated herein by reference.

  Chewing gum is prepared by use of the gum base of Example 1 formulated according to Table 1. Conventional mechanical mixing procedures are used with only mild heating.

  The gum base and filler are mixed in a mixing can equipped with mixing means such as a horizontally installed Z-shaped stirring arm. The can was preheated to a temperature up to about 50 ° C.

  When the contents are homogeneous, add the other ingredients according to the specified time schedule. Nicotine is added in the first half of the mixing process.

  The piece (piece) may be blended so that the nicotine per piece is 0.1 to 8 mg, preferably 2 to 4 mg. The strips evaluated contained 2 mg nicotine per strip.

  The chewing gum was coated using a hard coating. The coating can be applied, for example, according to the method disclosed in US Pat. No. 6,627,234, incorporated herein by reference.

The release of active substance in Examples 2 to 4 and two commercial products is measured in vitro. The in vitro test consists of a chewing machine (European Pharmacopeia 4 th. ed. 2.9.25 Chewing gum medical, drug release from) at a specified time interval of 0, 1, 2, 3, 5, 7 Performed by chewing in pH 7.4 phosphate buffer at 5, 10, 20 and 30 minutes.
The results are illustrated and described below.

  FIG. 1 is a graph representing the release profiles of two prior art nicotine chewing gums as a function of time.

  It is noted that very early and intermediate releases are relatively low over normal smoking times, i.e. times corresponding to 5 to 8 minutes. The release rate from 0 to 1 minute is even lower than the later intermediate release.

These two prior art nicotine chewing gums PA1 and PA2 are both intended for use in chewing for about 30 minutes. In other words, the accumulation of nicotine in the blood of the intended user is a process that lasts for a fairly long time.
It is noted that both nicotine chewing gums appear to release relatively linearly.

FIG. 2 is a graph representing the release of FIG. 1 at discrete time intervals for the chewing gums PA1 and PA2 described above over a 30 second time interval over the initial 0-5 minute chewing time. In other words, it is one of the differential illustrations of emission focusing on the emission at individual partial times of the emission time shown. As shown in the figure, the partial time for obtaining the values is 0 to 0.5 minutes, 0.5 to 1 minute, 1 to 1.5 minutes, 1.5 to 2 minutes, 2 to 2.5 minutes, 2 5 to 3 minutes, 3 to 3.5 minutes, 3.5 to 4 minutes, 4 to 4.5 minutes, 4.5 to 5 minutes.
The very early and mid-term releases are relatively slow over a relatively long period of time compared to normal smoking time, despite the fact that the release shown in FIG. 1 appeared to be relatively constant. It is noticed that it increases.

  FIG. 3 is a graph representing the initial and mid-term release of three chewing gums I1, I2 and I3 that apply according to the present invention. The release, i.e. the movement of the chewing gum out of the chewing gum, is illustrated in the same way as the prior art chewing gum of FIG.

  The illustrated chewing gum benefits from an initial favorable release throughout the critical time of the first 5 to 8 minutes of smoking. It is therefore noted that the release will never be less than 2% per partial time, ie 30 seconds. In other words, when chewing gum is applied according to the present invention, a certain amount of nicotine may be available for movement through the mucosa into the blood.

  It is also noted that mastication I3 is characterized by a very pronounced release during the first few minutes of mastication, thereby facilitating rapid release due to the fact that high osmotic pressure on the mucosa can be maintained from the very beginning. Is done.

  It is further noted that chewing gums I1 and I2 are characterized by a very constant release over the first 5 minutes of chewing. This can be considered very advantageous, for example, when adapted to taste problems associated with nicotine in the mouth.

FIG. 3 represents the release results obtained when chewing nicotine chewing gum with a chewing machine.
According to the present invention, a nicotine chewing gum having the properties illustrated in FIG. 3 can be applied by the following process steps.

  A nicotine chewing gum, such as I1, I2 or I3, is provided to a user with a human body. The human user can then chew the selected nicotine chewing gum and obtain a quick relief for craving by moving nicotine from the nicotine chewing gum through the mucosa into the user's blood.

  The applied nicotine chewing gum is characterized by the transfer of nicotine from the chewing gum that exceeds a selected transfer rate threshold between about 0.5 minutes and about 2.5 minutes from the start of the chewing, so that A constant osmotic pressure can be maintained on the mucosa for a long intermediate time. Thus, rapid relaxation was in accordance with one embodiment of the present invention.

  It is noted that none of the chewing gums applied by the present invention is characterized by the transfer of nicotine from the chewing gum, less than 2 mg nicotine per 30 seconds. It is also noted that, for example, I2 is characterized by a sustained dose that is never less than 4 mg per 30 seconds.

  FIG. 4 illustrates the initial and intermediate release from the chewing gums PA1, PA2, I1, I2 and I3 discussed above over the first approximately 8 minutes of the chewing process. It is noted that those that release most rapidly tend to level off after about 4 to 5 minutes of chewing.

Claims (37)

A chewing gum for releasing tobacco alkaloids,
The chewing gum comprises a polymer system in an amount of 2 to 99% by weight, a flavoring agent in an amount of 0.001 to 30% by weight and a sweetener in an amount of 2 to 80% by weight;
The polymer system comprises an elastomer in an amount of 0.1 to 10% by weight of the chewing gum;
The polymer system comprises an elastomer plasticizer in an amount of 2 to 30% by weight of the chewing gum; and
Every 30 seconds from 0.5 to 2.5 minutes from the start of the chewing process on a chewing machine with a pH 7.4 phosphate buffer (European Pharmacopia 4 th. ed. 2.9.25) A chewing gum that releases in vitro at least 2% of the tobacco alkaloids contained in the chewing gum before chewing.   The chewing gum of claim 1, wherein the tobacco alkaloid comprises nicotine.   Chewing gum according to claim 1 or 2, wherein the chewing gum is a compressed chewing gum tablet. The tobacco alkaloid contained in the chewing gum before chewing is released at least 2.5% in vitro every 30 seconds from 0.5 to 2.5 minutes from the start of the chewing process. The chewing gum of any one of these. 5. The in vitro release of at least 3% of tobacco alkaloids contained in the chewing gum before chewing every 30 seconds from 0.5 to 2.5 minutes from the start of the chewing process. The chewing gum according to claim 1. 6. The tobacco alkaloid contained in the chewing gum before chewing is released at least 5% in vitro every 30 seconds from 0.5 to 2.5 minutes from the start of the chewing process. The chewing gum according to claim 1. The tobacco alkaloid contained in the chewing gum before chewing is released at least 2% in vitro every 30 seconds from 2.5 to 5 minutes from the start of the chewing process. The chewing gum according to item. The tobacco alkaloid contained in the chewing gum before chewing is released at least 3% in vitro every 30 seconds from 2.5 to 5 minutes from the start of the chewing process. The chewing gum according to item. The tobacco alkaloid contained in the chewing gum before chewing is released at least 4% in vitro every 30 seconds from 5 to 10 minutes from the start of the chewing process according to any one of claims 1-8. The chewing gum described. 10. The in vitro release of at least 2 to 10% of tobacco alkaloid contained in the chewing gum before chewing during a time period of 0 to 30 seconds from the start of the chewing process. Chewing gum. 11. The in vitro release of less than 14% of the tobacco alkaloids contained in the chewing gum before mastication from 0 seconds to 2.5 minutes from the start of the chewing process. Chewing gum. The chewing gum according to any one of claims 1 to 11, wherein a maximum of 18% of the tobacco alkaloid contained in the chewing gum before chewing is released in vitro for a period of 10 to 30 minutes from the start of the chewing process. The tobacco alkaloid contained in the chewing gum before chewing is released at least 0.03 mg in vitro every 30 seconds from 0.5 to 2.5 minutes from the start of the chewing process. The chewing gum of any one of Claims. The tobacco alkaloid contained in the chewing gum before chewing is released at least 0.05 mg in vitro every 30 seconds from 0.5 to 2.5 minutes from the start of the chewing process. The chewing gum of any one of Claims. The tobacco alkaloid contained in the chewing gum before chewing is released at least 0.08 mg in vitro every 30 seconds from 0.5 to 2.5 minutes from the start of the chewing process. The chewing gum of any one of Claims.   The tobacco alkaloid contained in the chewing gum before chewing is released at least 0.03 mg every 30 seconds from 2.5 to 5 minutes from the start of the chewing process. The chewing gum according to item. The tobacco alkaloid contained in the chewing gum before chewing is released at least 0.05 mg in vitro every 30 seconds from 2.5 to 5 minutes from the start of the chewing process. The chewing gum according to item 1. 18. The tobacco alkaloid contained in the chewing gum before chewing is released at least 0.08 mg in vitro every 30 seconds from 2.5 minutes to 5 minutes from the start of the chewing process. The chewing gum according to item 1. 19. Chewing gum according to any one of the preceding claims, wherein at least 0.5 mg of tobacco alkaloid is released in vitro within the first 5 to 8 minutes of the chewing process.   20. A chewing gum according to any one of the preceding claims, wherein different parts of the chewing gum are targets for tobacco alkaloid migration at different times of the chewing process or at different times.   The chewing gum according to any one of claims 1 to 20, wherein the chewing gum includes a coating, and the coating includes a tobacco alkaloid.   The chewing gum according to any one of claims 1 to 21, wherein the chewing gum comprises a substantially hydrophilic polymer.   The chewing gum according to any one of claims 1 to 22, wherein the tobacco alkaloid is contained in an ion exchange resin.   24. The chewing gum according to any one of claims 1 to 23, wherein the tobacco alkaloid contains a salt of nicotine.   25. The chewing gum according to any one of claims 1 to 24, wherein the tobacco alkaloid comprises nicotine in its free form.   The chewing gum according to any one of claims 1 to 25, wherein the tobacco alkaloid is buffered.   27. The chewing gum according to any one of the preceding claims, wherein the chewing gum comprises an amount of 0 to 60% by weight of filler, an amount of flavoring of 0.001 to 30% by weight and an amount of sweetening of 2 to 80% by weight. The chewing gum described.   28. Chewing gum according to any one of the preceding claims, wherein the chewing gum comprises a high intensity sweetener in an amount of 0.001 to 3% by weight and a flavoring agent in an amount of 0.001 to 30% by weight.   29. Chewing gum according to any one of the preceding claims, wherein the polymer system comprises an elastomer in an amount of 2 to 10% by weight of the chewing gum.   30. Chewing gum according to any one of the preceding claims, wherein the polymer system comprises an elastomer plasticizer in an amount of 5 to 30% by weight of the chewing gum.   31. Chewing gum according to any one of the preceding claims, wherein the polymer system comprises wax in an amount of 0 to 30% by weight of the chewing gum.   32. Chewing gum according to any one of the preceding claims, wherein the polymer system comprises a softening agent in an amount of 2 to 30% by weight of the chewing gum.   33. Chewing gum according to any one of the preceding claims, wherein the polymer system comprises a filler in an amount of 0 to 50% by weight of the chewing gum.   34. Chewing gum according to any one of claims 1 to 33, wherein the polymer system comprises an antioxidant in an amount of 0 to 5% by weight of the chewing gum. 35. Chewing gum according to any one of claims 1 to 34, wherein the chewing gum comprises 2 to 4 mg of nicotine. The chewing gum according to any one of claims 1 to 35, wherein the chewing gum comprises 2 mg of nicotine. 37. Chewing gum according to any one of the preceding claims, wherein the chewing gum comprises 0.1 to 75% by weight of an outer coating.

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