CN102871987A

CN102871987A - Method for providing fast relief for user through nicotine chewing gum

Info

Publication number: CN102871987A
Application number: CN2012103283408A
Authority: CN
Inventors: 卡斯滕·安德森
Original assignee: Fertin Pharma AS
Current assignee: Fertin Pharma AS
Priority date: 2004-11-30
Filing date: 2004-11-30
Publication date: 2013-01-16

Abstract

The invention relates to a method for providing a fast relief for a user through a nicotine chewing gum, which comprises the following steps of: providing at least one chewing gum containing nicotiana alkaloids for the user, and transferring the nicotiana alkaloids into the body of the user by chewing the chewing gum, thereby relieving the nicotine desire of the user; and chewing the chewing gum comprises the following chewing process that the nicotiana alkaloids are transferred from the chewing gum at the speed more than a threshold transferring speed from about one second minute to about twenty-one second minute of starting of the chewing process.

Description

Nicotine chewing gum provides the method for rapid recovery to user

The application is that application number is 200480044489.7, denomination of invention is divided an application for the application of " nicotine chewing gum provides the method for rapid recovery to user ", and this mother's case application is the application that the PCT application PCT/DK2004/000833 that submitted on November 30th, 2004 enters the China national stage.

Background technology

Thirst for or addiction:

The medical science of the U.S. and scientific community think that nicotine makes us habit-forming.Nicotine meets psychology and the physiological standard of addiction:

Psychology-can can't help using it to the people of something addiction, and ignore its negative effect healthy to them or life.Good example is exactly someone ceaselessly smoking, even the infringement that lung has been caused owing to smoking makes them breathe with oxygen cylinder.

Physiology-neurosurgeon thinks that anything of the award approach in the brain opened all make us habit-forming.Because stimulate this neural circuit to make you feel that very well, you will ceaselessly do it to review those sensations repeatedly.

When the smoking of smoker's cut---health can not move in mode as before in the situation about suffering for want of medical supplies, and the physiological effect of nicotine is kept at least in a short time.They will experience: agitation, anxiety, depression and serious hope nicotine.

These symptoms and physiological change disappear after a period of time.During this, for successfully smoking cessation, alternative method essential of sending nicotine.

Nicotine:

Nicotine accounts for about 5 % by weight of tobacco plant usually.Depend on brand, medicated cigarette is contained the 8-20mg nicotine, but the 1mg that in fact only has an appointment when your smoking is absorbed by your health.

The impact of nicotine is of short duration, only continues 40 minutes to two hours.This cause people in one day periodically smoking to take nicotine to self.During sucking 10-15 second, most of smoking area is in the arduous process of nicotine impact.

Can take diverse ways with the opposing serious hope relevant with shortage nicotine in the blood.

Many pharmacotherapys have been developed or have explored to help the smoker to stop smoking.Main pharmacotherapy is Nicotine replacement therapy.Nicotine replacement therapy comprises by suitable delivery system management nicotine.Nicotine replacement product available on the market comprises nicotine transdermal patches, inhaler, nicotine nasal spray or nicotine chewing gum.As medicated cigarette, the product of these types diffuses through skin or mucosa by nicotine and nicotine is sent in the blood.

Nicotine transdermal patches is released into nicotine in the blood flow by skin.Every day with patch be applied to dried, wet, without the zones of different of hair skin and keep such as on the Product labelling of a specified duration the recommendation-be generally the intraday non-length of one's sleep.Use this product blood to be produced the nicotine of constant low concentration in during applying.

From pump type bottle, will in nicotine nasal spray suction people's the nose and by the intranasal layer it be absorbed in the blood flow.The nicotine delivery system of this form almost produces the quick increase of nicotine concentration fastly in blood as medicated cigarette.

Nicotine suction device enters in the user mouth by the mouth that connects plastic cartridge casep.Although this product is called as " inhaler ", it is delivered to nicotine in the lung unlike medicated cigarette.Nearly all nicotine only arrives oral cavity and throat, and nicotine is absorbed by mucosa there.

Nicotine chewing gum is by the oral cavity internal layer, and namely mucosa is released into nicotine in the blood flow.Chewing gum for joyful is different from chewing, nicotine chewing gum requires the program of standard-it is slowly chewed until slight tingling occurs or acid produces, and then places it between obstacle and the chewing gum (check and gum) until this taste or tingling almost disappear.To each chewing gum, this circulation repeats about 30 minutes usually.The available product of chewing through originally 10-15 minute has slowly increased nicotine blood concentration.

The present invention relates to thirst for by the chewing gum opposing that contains nicotine.

Thirst in this area well-known by the chewing gum opposing that contains nicotine like this.

Basically follow in the prior art two kinds of different approaches, be used alone or in combination.

Then method originally makes the whole release of chewing gum in the phase and the release coupling of whole required nicotine of chewing for nicotine is mixed in the chewing gum.Compare from once or for several times different Smoking Patterns, common this method comprises the consideration to the release of nicotine in a day.

Improve by chewing gum another of the opposing thirsted for attempted as in the coating that nicotine is mixed coated chewing gum for example.This method can be referred to as two-stage method in this area, namely the method provides initial remarkable nicotine dosage immediately behind the beginning chew gum, then the follow-up for a long time dosage that provides for the second time.This subsequent dose also is called as maintenance dose, and it is sustainable about 10 to 30 minutes process of chewing for example.

The expectation that yet the existing problem of prior art may especially not liked predose and subsequent dose usually for some chewing gum user and user alleviates the serious hope of nicotine is not mated.

Purpose of the present invention is for obtaining a kind of chewing gum, use this chewing gum not only after use but also in use can be effectively and user resist acceptably serious hope.

Summary of the invention

The present invention relates to a kind of method that nicotine is thirsted for that alleviates, it comprises the steps:

Provide at least a chewing gum that comprises nicotiana alkaloids to user;

Make nicotiana alkaloids be transferred to the human body of described user and provide alleviating that nicotine thirsts for to described user from chewing gum by chewing described chewing gum,

Described the chewing of wherein said chewing gum comprises the following process of chewing: with greater than the speed of threshold value transfer velocity at about 1/2 minute that begins from the described process of chewing to about 2 ¹/ ₂In the minutes nicotiana alkaloids is shifted out from described chewing gum.

According to the present invention, in interstage of the process of chewing nicotine or the transfer that is generally nicotiana alkaloids are maintained the threshold value transfer velocity, thereby be easy to favourable and effectively alleviate fast, this is owing to for example compare with the transfer of the nicotine of chewing the process later stage, has affected significantly the sensation of nicotine and is therefore alleviated in the transfer in this concrete period.Especially it should be noted that the present invention desired " effectively alleviating (relief kick) " relates to: chew the time of usually ignoring in the process, be also referred to as the interstage, for human body provides the required nicotine dosage of remarkable deal, because this special time was commonly used in the time of smoking.

According to the present invention, the threshold value transfer velocity is interpreted as the minimum speed that nicotine shifts in given interval.In other words, can use within the scope of the present invention greater than the transfer velocity of this minimum speed.2 ¹/ ₂Minute corresponding to 150 seconds.

According to the present invention, have recognized that the existing problem of prior art is for almost can not get alleviating of chewing gum user or being slowly at least when comparing with smoking.Also have realized that the amount of the nicotine that the measure of the prior art that relates to this problem is usually directed to discharge and basically seldom consider how to finish the actual transfer of nicotine from chewing gum.This is for based on discharging and be the fact for the quick release of nicotine in the coating for example conventional for a long time through what chewing the time in about 30 minutes.Therefore have realized that nicotine as if for example the initial several seconds very fast release from coating is very little on the impacts in initial 5 to 10 minutes of chewing, because most of nicotine is swallowed and only is transferred in the blood by metabolism.

Transfer velocity should be interpreted as nicotine or the nicotiana alkaloids transfer velocity from the chewing gum to the outside according to the present invention, i.e. rate of release, but the substantially required performance of chewing gum also comprises the transfer from chewing gum to relevant blood of human body.This rate of release for example can be measured within 30 seconds sub-time period.

Term " nicotiana alkaloids " refers to nicotine or nicotine Alkaloid such as nornicotine, the antabac etc. of acceptable acid-addition salts form on free alkali or the pharmacology in the present invention.The plant alkaloid of the type can be by being the tobacco varieties in nicotine and nornicotine source and being Lobelia and the acquisition of Lobeliaceae (Nicotiana bigelovi) kind in antabac source.

In addition, it should be noted that usually the instantiation that nicotine specifically is called for the activating agent of thirsting in no case can limit the invention in the scope of using other nicotiana alkaloids aspect for identical specific purposes with explaining.Anywhere only specifically mentioning of nicotine is used for illustrating purpose of the present invention rather than in order to get rid of alternative functional equivalent with tangible form in this application.

Usually it should be noted that nicotine is preferred nicotiana alkaloids.

In the present invention, the term nicotine comprise any type of nicotine or nicotine derivant with and any pharmaceutically acceptable salt, coordination compound or solvate, wherein any form is such as being physical form such as amorphous, crystal, polymerphous etc. or chemical species such as isomer and enantiomer etc.Nicotine can be selected from nicotine alkali, nicotine hydrochlorate, nicotine dihydrochloride, nicotine list tartrate, nicotine two tartrates, nicotine sulfate, nicotine zinc chloride such as zinc chloride monohydrate and nicotine Salicylate.

Comprise nicotine in nicotiana alkaloids described in the embodiment of the present invention.

Refer to that in transfer velocity described in the embodiment of the present invention nicotine is transferred to the outside of chewing gum from chewing gum.

According to favourable embodiment of the present invention, the time of chewing can shorten greatly because of at least two different reasons, at first: because measure user of the present invention obtains to alleviate relatively rapidly, secondly: in blood, only keep nicotine and appear as dynamically rather than static process, thereby so that compare with alleviating fast of initial serious hope, user does not more wish only to make the lasting nicotine that keeps.

In the transfer velocity of threshold value described in the embodiment of the present invention at about 1/2 minute that begins from the described process of chewing to about 2 ¹/ ₂The sub-time period inner evaluation of minutes.

According to an embodiment of the present invention, 30 seconds sub-time period can be advantageously used in and confirm whether transfer velocity is kept.Measuring transfer velocity therefore verified in 30 seconds is enough for obtaining quick release.Therefore when application during 30 seconds sub-time period, transfer should be followed four sub-time periods, namely 1/2-1 minute, 1-1 ¹/ ₂Minute, 1 ¹/ ₂-2 minutes and 2-2 ¹/ ₂Minute the sub-time period in the requirement that limits.

Be apparent that transfer velocity even can within shorter sub-time time period, measure, for example can use 15 second time.Also can use long sub-time period or the sub-time period of different length, but be the reduction of nicotine or nicotiana alkaloids transfer in the dispose procedure in the middle of avoiding or the carefully selection time that descends.Especially according to the present invention in intermediate transfer, namely about 1/2 to 2 ¹/ ₂Should avoid in minute descending, slow down because this decline can cause shifting inevitably, although the fact is the fully release height of nicotine.

In embodiment of the present invention, described the chewing of described chewing gum comprises the following process of chewing: begin from the described process of chewing about 2 ¹/ ₂Minute to about 10 minutes, preferably from the described process of chewing begin about 2 ¹/ ₂Minute from described chewing gum, shift nicotiana alkaloids with the speed greater than another threshold value transfer velocity to about 5 minutes.

According to another embodiment of the present invention, chew initial 2 ¹/ ₂Can be with another threshold application in the process of chewing after minute.Therefore, this threshold value of favourable embodiment according to the present invention should preferably be guaranteed 2 ¹/ ₂Minute until 10 or time of preferred at least 5 minutes in obtain higher nicotiana alkaloids and shift.

Can keep alleviating of initial gained by this way.

The transfer velocity of threshold value described in the embodiment of the present invention cause being included in chew before nicotiana alkaloids in the described chewing gum at 1/2 minute that begins from the described process of chewing to about 2 ¹/ ₂Discharged at least 2% every 30 seconds in the minutes, preferably at least about 2.5%.

According to an embodiment of the present invention, the nicotiana alkaloids of chewing discharged at least 2% every 30 seconds, and preferably at least 2.5%, thus when chewing, keep hyperosmosis to mucosa.This initial set constant nicotiana alkaloids that obtains within keeping the oral cavity should preferably obtain alleviating fast and thisly desirablely alleviating fast that not only to require be accidental or release stage of postponing but also require is kept nicotiana alkaloids constant high availability in the oral cavity at least in the common desired part-time of smoking of user being even more important in early days of the process of chewing because compare with the chewing gum that routine contains nicotiana alkaloids very fastly.

The transfer velocity of threshold value described in the embodiment of the present invention cause being included in chew before nicotiana alkaloids in the described chewing gum at about 1/2 minute that begins from the described process of chewing to about 2 ¹/ ₂Discharged at least 3% every 30 seconds in the minutes, preferably at least about 4%.

According to an embodiment of the present invention, the nicotiana alkaloids of chewing discharged at least 3% every 30 seconds, and preferably at least 4%, thus when chewing, keep hyperosmosis to mucosa.This initial set constant nicotiana alkaloids that obtains within keeping the oral cavity should preferably obtain alleviating fast and thisly desirablely alleviating fast that not only to require be accidental or release stage of postponing but also require is kept nicotiana alkaloids constant high availability in the oral cavity at least in the common desired part-time of smoking of user being even more important in early days of the process of chewing because compare with the chewing gum that routine contains nicotiana alkaloids very fastly.

The transfer velocity of threshold value described in the embodiment of the present invention cause being included in chew before nicotiana alkaloids in the described chewing gum at about 1/2 minute that begins from the described process of chewing to about 2 ¹/ ₂Discharged at least 5% every 30 seconds in the minutes, preferably at least about 6%.

According to another favourable embodiment of the present invention, high level can be set up and maintain to transfer velocity, improves alleviating fast of user thereby it is characterized by.

The transfer velocity of threshold value described in the embodiment of the present invention cause being included in chew before in the described chewing gum nicotiana alkaloids begin from the described process of chewing about 2 ¹/ ₂Minute discharged at least 2% every 30 seconds to about 5 minutes, preferably at least 3%.

According to another favourable embodiment of the present invention, after the process of chewing begins about 2 ¹/ ₂Also should to remain high speed available for nicotiana alkaloids minute to 5 minutes.It should also be noted that and the basically any time in the 2.5-5 that begins from the described process of chewing minute interval all to follow this threshold velocity.

The transfer velocity of threshold value described in the embodiment of the present invention cause being included in chew before in the described chewing gum nicotiana alkaloids begin from the described process of chewing about 2 ¹/ ₂Minute discharged at least 3% every 30 seconds to about 5 minutes, preferably at least 3.5%.

According to another favourable embodiment of the present invention, after the process of chewing begins about 2 ¹/ ₂Nicotiana alkaloids also should keep and can obtain at a high speed minute to 5 minutes.It should also be noted that and the in fact any time in 2.5 to 5 minutes the interval that the process of chewing begins to follow this transfer velocity.

In embodiment of the present invention, wherein said threshold value transfer velocity cause being included in chew before nicotiana alkaloids in the described chewing gum to about 10 minutes, discharged at least 4% every 30 seconds at about 5 minutes that begin from the described process of chewing, preferably at least 5%.

The transfer velocity of threshold value described in the embodiment of the present invention cause being included in chew before nicotiana alkaloids in the described chewing gum discharge at least 2-10% in about 0 second to about 30 second time beginning from the described process of chewing, preferably at least 5%.

The transfer velocity of threshold value described in the embodiment of the present invention cause being included in chew before nicotiana alkaloids in the described chewing gum at about 0 second that begins from the described process of chewing to about 2 ¹/ ₂Release in the minutes is less than 14%, preferably less than 12%.

According to an embodiment of the present invention, the initial transfer of nicotiana alkaloids from chewing gum should keep below be included in chew before the 12-14% of nicotiana alkaloids in the described chewing gum burn or tingling to avoid so-called.In addition, for example the too many release of nicotine can cause on the other hand the nicotine of part release to be swallowed and therefore only shift onset by metabolism.

The transfer velocity of threshold value described in the embodiment of the present invention cause being included in chew before nicotiana alkaloids in the described chewing gum beginning from the described process of chewing about 10 be released into to about 30 minutes many 18%, preferably at the most 15%.

The transfer velocity of threshold value described in the embodiment of the present invention cause being included in chew before nicotiana alkaloids in the described chewing gum at about 1/2 minute that begins from the described process of chewing to about 2 ¹/ ₂Discharged at least 0.03mg in the minutes every 30 seconds, preferably 0.04mg at least.

According to the present invention in the blood accumulation of nicotine or nicotiana alkaloids should be preferably by obtaining such as the osmotic pressure of keeping oral mucosa in initial 10 minutes of the process of chewing in process mid-term chewing.

The transfer velocity of threshold value described in the embodiment of the present invention cause being included in chew before nicotiana alkaloids in the described chewing gum at about 1/2 minute that begins from the described process of chewing to about 2 ¹/ ₂Discharged at least 0.05mg in the minutes every 30 seconds, preferably 0.06mg at least.

The transfer velocity of threshold value described in the embodiment of the present invention cause being included in chew before nicotiana alkaloids in the described chewing gum at about 1/2 minute that begins from the described process of chewing to about 2 ¹/ ₂Discharged at least 0.08mg in the minutes every 30 seconds, preferably 0.1mg at least.

The transfer velocity of threshold value described in the embodiment of the present invention cause being included in chew before in the described chewing gum nicotiana alkaloids begin from the described process of chewing about 2 ¹/ ₂Discharged at least 0.03mg to about 5 minutes every 30 seconds, preferably 0.04mg at least.

The transfer velocity of threshold value described in the embodiment of the present invention cause being included in chew before in the described chewing gum nicotiana alkaloids begin from the described process of chewing about 2 ¹/ ₂Discharged at least 0.05mg minute to about 5 minutes every 30 seconds, preferably 0.06mg at least.

In embodiment of the present invention, wherein said threshold value transfer velocity cause being included in chew before in the described chewing gum nicotiana alkaloids begin from the described process of chewing about 2 ¹/ ₂Discharged at least 0.08mg to about 5 minutes every 30 seconds, preferably 0.1mg at least.

In embodiment of the present invention at least the 0.5mg nicotiana alkaloids in initial 10 minutes of the process of chewing or preferably chewing in initial 5-8 minute of process and discharge.

Should obtain according to an embodiment of the present invention even higher release, for example at least the 0.8mg nicotiana alkaloids in initial 10 minutes of the process of chewing or preferably chewing in initial 5-8 minute of process and discharge.

In embodiment of the present invention, wherein the different piece of chewing gum is the target nicotiana alkaloids that shifts in the constantly different or different time of the process of chewing.

According to an embodiment of the present invention, the different piece of chewing gum can be the target nicotiana alkaloids that shifts in the constantly different or different time of the process of chewing, thereby be easy to obtain to chew process corresponding period, i.e. usually the desirable constant transfer in initial 3-5 minute of the process of chewing or desirable at least minimum the transfer.Therefore can increase by the coating that for example contains nicotine the transfer that begins most of nicotiana alkaloids, namely chew the initial several seconds transfer of process.Perhaps, nicotine can be included in pearl or other sustained-release materials.Other material also can comprise the mixture of the different polymer with different release performances.Other material can comprise dissimilar buffer agents.

Therefore the threshold value transfer velocity is by obtaining in conjunction with the different piece with chewing gum of different release profiles.

In embodiment of the present invention, wherein said chewing gum comprises coating, and wherein said coating comprises nicotiana alkaloids.

According to an embodiment of the present invention, nicotiana alkaloids is included in the coating and therefore can discharges very rapidly in the earliest stages of the process of chewing.

In embodiment of the present invention, described chewing gum comprises substantially hydrophilic polymer.

In embodiment of the present invention, the variation of transfer velocity is minimized.

According to an embodiment of the present invention, should avoid nicotiana alkaloids significant change in time to hide to obtain the favourable sense of taste.Therefore unexpected nicotiana alkaloids peak value can be difficult to hide taste, especially when relating to the peak value that occurs after the process of chewing that begins most.Following I1 and I3 are the example of this level and smooth release.

In embodiment of the present invention, wherein said nicotiana alkaloids is included in the ion exchange resin.

Be Andrea Pollack phosphorus nicotine (nicotine polacrilex) according to the embodiment nicotiana alkaloids.

In embodiment of the present invention, wherein said nicotiana alkaloids comprises the salt of nicotine.

The nicotine that comprises free form in nicotiana alkaloids described in the embodiment of the present invention.

In embodiment of the present invention, nicotiana alkaloids is cushioned.

The process of chewing in embodiment of the present invention is less than 30 minutes, preferably less than 20 minutes.

Should keep the short process of chewing to simulate the ultimate principle that alleviates fast that obtains to follow by the ideal to smoking process according to embodiment.

In embodiment of the present invention, chew the time match of process and smoking.

Comprise about 2 polymeric systems to about 99 % by weight at chewing gum described in the embodiment of the present invention, about 0.001 spice and about 2 sweeting agents to about 80 % by weight to about 30 % by weight.

Comprise about 0 filler to about 60 % by weight at chewing gum described in the embodiment of the present invention, about 0.001 spice and about 2 sweeting agents to about 80 % by weight to about 30 % by weight.

Comprise about 0.001 high-intensity sweeteners and about 0.001 spice to about 30 % by weight to about 3 % by weight at chewing gum described in the embodiment of the present invention.

Comprise at polymeric system described in the embodiment of the present invention and to account for chewing gum weight about 0.1 to about 40%, preferably account for the elastomer of chewing gum weight about 2 to about 10%.

Comprise at polymeric system described in the embodiment of the present invention and to account for chewing gum weight about 2 to about 60%, preferred about 5 to about 30% elastomer elasticizer.

In embodiment of the present invention, described polymeric system comprises and accounts for chewing gum weight about 0 to about 30%, preferred about 0 to about 15% wax.

Comprise at polymeric system described in the embodiment of the present invention and to account for chewing gum weight about 2 to about 30%, preferably account for the softening agent of chewing gum weight about 5 to about 20%.

Comprise at polymeric system described in the embodiment of the present invention and to account for chewing gum weight about 0 to about 50%, preferably account for the filler of chewing gum weight about 0 to about 30%.

Comprise at polymeric system described in the embodiment of the present invention and to account for chewing gum weight about 0 to about 5%, preferably account for the antioxidant of chewing gum weight about 0 to about 2%.

In embodiment of the present invention, chew at least described chewing gum of a slice at every turn.

In embodiment of the present invention, chew at least two described chewing gum at every turn.

In embodiment of the present invention, chewed at least described chewing gum of a slice in one day.

In embodiment of the present invention, when thirsting for nicotine, someone chews at least described chewing gum of a slice.

According to favourable embodiment of the present invention, contain the chewing gum of nicotiana alkaloids even can use just to the serious hope that reacts on user.In other words, can avoid keeping high nicotine concentration in the blood always.

In embodiment of the present invention, when need to comprising the treatment of nicotiana alkaloids or nicotine, someone chews at least described chewing gum of a slice.

Description of drawings

With reference now to following accompanying drawing, present invention is described:

Fig. 1 shows the release profiles of prior art nicotine chewing gum,

Fig. 2 be presented at prior art nicotine chewing gum in the middle of the decomposition of release in 30 seconds intervals discharging,

Fig. 3 is presented at the decomposition that discharges in middle 30 seconds intervals that discharge of using nicotine chewing gum of the present invention, and

Fig. 4 shows the release profiles of the combination of prior art chewing gum and chewing gum of the present invention.

The specific embodiment

Common, but chewing gum compositions comprises water solublity body part, water-insoluble Chewing gum base section and flavoring agent usually.In the process of chewing along with the time water-soluble portion has consumed part spice.Wholely chew that gum base partly is retained in the mouth in the process.The term chewing gum refers to masticatory pattern and this two types the chewing gum of bubble type on the ordinary meaning.

Gum base is the material of chewing of chewing gum, and it gives the final products chew characteristics.Gum base usually defines the release profiles of spice and sweeting agent and plays an important role in chewing gum product.

The insoluble part of chewing gum can contain any combination of elastomer, polyvinyl, elastomer elasticizer, wax, softening agent, filler and other optional member such as coloring agent and antioxidant usually.

Depend on specific product to be prepared and depend on that final products are desirable and chew and other sense quality, but the composition significant change of gum base formulation.Yet, the typical range (% by weight) that above-mentioned gum base forms is: 5-50 % by weight elastomer compounds, 5-55 % by weight elastomer elasticizer, 0-40 % by weight wax, 5-35 % by weight softening agent, 0-50 % by weight filler and other composition of 0-5 % by weight such as antioxidant, coloring agent etc.

Elastomeric function

Elastomer provides rubbery, cohesion characteristic for chewing gum, and this characteristic depends on that the chemical constitution of this composition changes with its mode of mixing with other composition.The elastomer that is suitable for gum base of the present invention and chewing gum can comprise natural or synthesis type.

Elastomer

Elastomer can be any insoluble polymer as known in the art, comprise that those are at Food and Drug Administration, CFR, Title 21, Section 172, the chewing gum polymer that is used for chew gum and bubble gum of listing with " Masticatory Substances of Natural Vegetable Origin " and " Masticatory Substances, Synthetic " in 615.

Useful natural elastomer comprises natural rubber such as sootiness or liquid latex and guayule, natural gum such as gelutong, sorva (Lechi caspi), perillo, sorva (sorva), massaranduba balata, the chocolate balata, red sandalwood glue (nispero), black apple glue, tunny gum (chicle), gutta-percha, ancient Taka is glue (gutta kataiu) too, Niger's gutta-percha, Ka Sidela glue, chilte glue, red Kui bar glue (chiquibul), Gu Ta Hang Kang glue (gutta hang kang).

Useful synthetic elastomer comprises elastomer such as BS, poly-isobutyl diene and the isobutylene-isoprene copolymer of high molecular, low-molecular-weight elastomer such as polybutene, polybutadiene and polyisobutylene, vinyl polymerization elastomer such as polyvinyl acetate, polyethylene, ethylenic copolymer elastomer such as vinyl acetate/vinyl laurate, vinyl acetate/stearic acid vinyl ester, Ethylene/vinyl acetate, polyvinyl alcohol or its mixture.

The butadiene-styrene types of elastomeric maybe can be referred to as SBR, is generally about 20: 80-60: 40 styrene: the copolymer of divinylic monomer.The elasticity of the scale effect SBR of these monomers, described elasticity is estimated by Mooney viscosity.With styrene: the butadiene ratio reduces, and Mooney viscosity reduces.

The structure of SBR is usually by consisting of with styrene copolymerized straight chain 1,3-butadiene and these elastomeric isomolecule characteristics being provided.The mean molecule quantity of SBR is＜600,000g/ mole.

The isobutylene-isoprene types of elastomeric maybe can be referred to as butyl rubber, and the mole percent concentration range of its isoprene is 0.2-4.0.Similar with SBR, along with isoprene: the isobutene. ratio reduces, and elasticity also reduces, and elasticity is measured by Mooney viscosity.

The structure of butyl rubber usually by with the 2-methyl isophthalic acid of branching 2-metering system (isobutene .) copolymerization, 3-butadiene (isoprene) consists of, and the same with SBR, the type structural property is non-linear.The mean molecule quantity of SBR is 150,000g/ mole to 1,000,000g/ mole.

The polyisobutylene types of elastomeric maybe can be referred to as PIB, is the polymer of 2-metering system and the same with SBR and butyl rubber, and its character is non-linear.The low-molecular-weight elastomer provides soft chew characteristics and also provides elasticity as other elastomer for gum base.Mean molecule quantity can be about 30,000 to 120,000g/ moles and penetrance can be about 4 millimeters to 20 millimeters.Penetrance is higher, and PIB is just softer.Similar with SBR and butyl rubber, high molecular weight elastomer provides elasticity for chewing gum.Mean molecule quantity can be 120,000-1,000,000g/ mole.

The mean molecule quantity of polybutene is about 5, and the 000g/ mole is to about 30, the 000g/ mole.

The function of polyvinyl

Vinyl polymerization and combined polymerization types of elastomeric provide anti-viscosity, change the chew characteristics of the chewing gum that is made by these gum base with polyvinyl and provide the hydrophilic of the sensation that benefits final chewing gum.

Polyvinyl

For vinyl copolymerization type, the amount that is present in vinyl laurate, stearic acid vinyl ester or ethylene in vinyl laurate/vinyl acetate (VL/VA), stearic acid vinyl ester/vinyl acetate (VS/VA) or Ethylene/vinyl acetate (EVA) the copolymer about 10-about 60% of copolymer weight that usually respectively does for oneself.The mean molecule quantity of these polymer can be for about 2, and the 000g/ mole is to about 100, the 000g/ mole.

The mean molecule quantity of polyvinyl such as polyvinyl alcohol and polyvinyl acetate is about 8, and the 000g/ mole is to about 65, the 000g/ mole.

Vinyl acetate polymer (PVAc) character is branching.When the copolymerization such as vinyl acetate monomer and vinyl laurate, stearic acid vinyl ester, ethylene, degree of branching increases.Degree of branching is higher, when with normal paraffin hydrocarbons and the wax blend of isoparaffin type or the compatibility when mixing just higher.

For example usually synthetic elastomer and the low-molecular-weight elastomer group of high molecular are share in gum base in the industry.The combination of the preferred synthetic elastomer of the present invention includes but not limited to the combination of polyisobutylene and styrene-butadiene, polyisobutylene and polyisoprene, polyisobutylene and isobutylene-isoprene copolymer (butyl rubber) and polyisobutylene, SB and isobutylene isoprene copolymer, and the mixture of all above-mentioned single synthetic polymers and each polyvinyl acetate, vinyl acetate-vinyl laurate copolymer or its mixture.

The function of elastomer elasticizer

Elastomer elasticizer changes the robustness of gum base.Chain interruption between its elastomer molecules (plasticising) follows the feature of the change of its softening point to cause final chewing gum firmness degree and the change of the compatibility when being used for gum base.This performance can be very important when someone wants to provide more resilient chain in for the situation of alkane at wax.

Elastomer elasticizer

Be suitable for elastomer elasticizer of the present invention and comprise the natural rosin ester that often is called as ester gum.This elastomer elasticizer that is known in the art is methyl ester, glyceride and the pentaerythritol ester of Colophonium and modified rosin, for example hydrogenation, dimerization and newtrex.Example is the methyl ester of pentaerythritol ester, wood rosin and Colophonium of pentaerythritol ester, part and complete all hydrogenated wood rosin and Colophonium of glyceride, wood rosin and Colophonium of glyceride, Talloil rosin of the wood rosin of glyceride, part two polymerizations of the wood rosin of glyceride, polymerization of glyceride, partial hydrogenation wood rosin and the Colophonium of wood rosin and Colophonium and Colophonium and Colophonium and part and the complete all hydrogenated methyl ester of wood rosin and Colophonium.

Synthetic elastomer elasticizer comprises the terpene resin derived from australene, nopinene and/or (R)-4-isopropenyl-1-methyl-1-cyclohexene.

The elastomer elasticizer that uses can be one type or the combination above a type.The ratio of common a kind of plasticizer and another kind of plasticizer depends on its softening point separately, the impact that spice is discharged with and separately with respect to the degree of being clamminess of glue.The ball of above-mentioned Colophonium esters can be about 45 ℃ to about 120 ℃ with the ring softening point.The softening point of terpene resin can be about 60 ℃ to about 130 ℃.

The function of wax

Pertroleum wax helps by the curing of the made final chewing gum of gum base and improves shelf life and texture.The crystalline size of wax affects the release of spice.Those waxes that are rich in isoparaffin are rich in the wax of normal paraffin hydrocarbons than those, and especially carbon number is little less than the crystalline size of the wax of 30 normal paraffin hydrocarbons.Less crystalline size so that spice than On The Drug Release because than the wax that has than the megacryst size, spice is more from the obstacle of escaping than the wax of small crystalline size.Compare with the gum base that is made by isoparaffin wax, the compatibility of the gum base that makes with the normal paraffin chloroflo is less.

Wax

Pertroleum wax (paraffin of refine and microwax) and paraffin are comprised of the isoparaffin of the normal paraffin hydrocarbons that is mainly straight chain and branching.The ratio of normal paraffin hydrocarbons and isoparaffin changes.

The carbon chain lengths of normal paraffin chloroflo usually＞C-18, and its most length is no longer than C-30.Be mainly the wax of normal paraffin hydrocarbons for those, branching and ring structure are positioned near the end of the chain.The viscosity of normal paraffin chloroflo is＜10mm ²/ s (at 100 ℃) and the number-average molecular weight that merges are＜the 600g/ mole.

The carbon chain lengths of isoparaffin wax is usually mostly greater than C-30.Be mainly branched chain in the wax of isoparaffin and ring structure along the carbochain random at those.The viscosity of isoparaffin wax is greater than 10mm ²/ s (at 100 ℃) and the number-average molecular weight that merges are＞the 600g/ mole.

Therefore synthetic wax is produced by atypical mode for pertroleum wax production and is not considered to pertroleum wax.Synthetic wax can comprise contain branched paraffin and with wax, polyethylene and Fischer Tropsch class wax such as but not limited to the monomer copolymerization of propylene.Tissuemat E is to contain the synthetic wax that is connected with the alkane unit of vinyl monomer on its of variation length.

Native paraffin can comprise rice bran wax, Cera Flava, Brazil wax or candelilla wax.

Wax can be used in combination separately or with any.

The function of softening agent

The selection of softening agent affects the pliability of gum base.Softening agent changes texture, makes the hydrophobic and hydrophilic component of gum base miscible, and the further synthetic elastomer of plasticising gum base.The emulsifying agent that belongs to the softening agent class provides performance in conjunction with water for gum base, and this has given the smooth surface of gum base pleasant and has reduced its adhesiveness.

Softening agent

The softening agent that is suitable for gum base comprises not hydrogenation, partial hydrogenation and the triglyceride of complete all hydrogenated vegetable oil and Adeps Bovis seu Bubali, cupu oil and degreased cocoa powder and emulsifying agent in addition to these.

Triglyceride comprises the triglyceride of Semen Gossypii, Petiolus Trachycarpi, palm kernel, Cortex cocois radicis, Flos Carthami, Semen Brassicae campestris, Helianthi, Adeps Bovis seu Bubali, Semen sojae atricolor, cupu oil, medium chain etc.

Compare with mainly containing stearic triglyceride, the caproic acid of triglyceride, sad, capric acid, myristic acid, lauric acid and PALM FATTY ACID are more prone to the plasticising synthetic elastomer.

Glyceryl monoacetate; diglyceride; acetylizad glyceryl monoacetate and diglyceride; glyceryl monoacetate and the diglyceride of distillation; glyceryl monostearate; propylene glycol monostearate; sodium stearate; potassium stearate; magnesium stearate; calcium stearate; glycerol triacetate, fatty acid monoglyceride (stearic acid for example; Palmic acid; oleic acid and linoleic acid), the monoglyceride of lactic acid and acetic acid and diglyceride; what be also referred to as Olestra comprises that those are disclosed in the sugar ester of the edible fat acid among the WO00/25598; lecithin and hydroxylated lecithin belong to emulsifying agent; make processing by it, wherein the overwhelming majority can contain the triglyceride less than 2 % by weight.

Comprise emulsifying agent softening agent can two or more be used in combination separately or at least.

The function of filler

The filler that is used for gum base changes the texture of gum base and helps processing.The cohesion of particle size influences gum base, density and processability and mixing thereof.Granularity is less, and final gum base is just finer and close and more cohesion.By select filler also can change the mixing of parent material based on particle size distribution, therefore so that can change the mixed characteristic of parent material in the gum base course of processing and the final chew characteristics of the chewing gum that made by these gum base.

Filler

The filler that is suitable for gum base comprises magnesium carbonate and calcium carbonate, hone limestone flour and silicates such as magnesium silicate and aluminium silicate, Kaolin and clay, aluminium oxide, silicon oxide, Talcum, and titanium oxide, one-lime phosphate, dicalcium phosphate and tricalcium phosphate, sodium sulfate, cellulosic polymer such as ethyl cellulose, methylcellulose and timber or its mixture.

Talc filler can be used in gum base of the present invention and the chewing gum, and it can contact or use acid spice or provide required sour environment with by preventing the artificial sweetener degraded with the reaction of Calcium carbonate filler with acid spice.The particle mean size of calcium carbonate and talc filler is generally about 0.1 micron to about 15 microns.

Filler also can comprise natural organic fiber such as fruit and vegerable fiber, corn, rice, cellulose and its combination.

The function of other optional member such as antioxidant, coloring agent and spice and list:

Antioxidant prolong gum base, final chewing gum or its separately component comprise shelf life and the storage of fat and perfumery oil.

The antioxidant that is suitable for gum base comprises butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), bata-carotene, tocopherol, acidulant such as vitamin C, propyl gallate, other synthetic and Natural Types or its mixture.

Spice and coloring agent are given characteristic or are removed or hide undesirable characteristic.Coloring agent can comprise FD﹠amp usually; C class color lake, plant extract, fruits and vegetables extract and titanium dioxide, spice can comprise cocoa powder, thermally-denatured aminoacid and other plant extract usually.

The preparation gum base

Gum base is usually by preparing in the Sigma's type blender that a certain amount of elastomer, elastomer elasticizer and filler and polyvinyl is in case of necessity joined heating (10 ℃-120 ℃), wherein the front and back speed ratio of blender is about 1.2: about 2: 1 of 1-, wherein the higher speed ratio is generally used for requiring its elastomeric gum base of fiercer mixing.

The initial content that comprises the composition of parent material can be determined to determine to reach suitable concordance and can and increase the required mixability of chain branching by the destruction elastomer by the ability to work of mixing tank.Initial packing density or to have a selection level of the filler that certain particle size distributes higher, mixability is the higher and therefore crosslinked fracture of more elastomer chains just, cause more branching of elastomer, therefore reduce the viscosity of gum base and therefore final gum base and the chewing gum that made by this gum base just softer.Incorporation time is longer, uses the glue group composition of getting over low-molecular-weight or softening point, and the viscosity of final gum base and solidness are just lower.

Mix in case composition flocks together and usually to begin effectively.Can be any time the length of incorporation time in 15-90 minute.

Preferred incorporation time is 20 minutes to about 60 minutes.The amount of the elastomer elasticizer that adds depends on the concentration of elastomer and the filler of existence.If add too many elastomer elasticizer, then parent material can too plastify and be inhomogeneous.

Initial Composition was evenly assembled and mixed after the desirable time, and what sequentially add glue group composition supplies surplus until obtain the fully evenly material of fusing.Usually any residue of elastomer, elastomer elasticizer, polyvinyl and filler adds in after the time 60 minutes of initial mixing.Usually with filler and elastomer elasticizer is weighed separately and within this time portioning add.Optional wax and softening agent add after elastomer and elastomer elasticizer He in next 60 minutes usually.Then make material before discharge, become even.

Depend on prescription, typical gum base process time can be about 1 in about 3 hours, and preferred about 1 ¹/ ₂-2 ¹/ ₂Change in hour.Final material temperature during discharge can be between 70 ℃ and 130 ℃, preferably between 100 ℃ and 120 ℃.The material of fully fusing is poured into from mixing tank in coating pan or the parcel dish (lined pan), extruded or be cast into any desirable shape and make its cooling curing.Those of skill in the art will appreciate that the many variations that can carry out said procedure in those this areas.

The water-soluble portion of chewing gum

Other component that the water-soluble portion of chewing gum can comprise softening agent, sweeting agent, high-intensity sweeteners, spice, acidulant, filler, antioxidant and desired attribute is provided.Softening agent consists of about 0.5 chewing gum to about 25.0 % by weight usually.Filler usually consists of about 5 to about 90%, preferred about 20 to about 80% chewing gum.High-intensity sweeteners in the chewing gum is generally about 0.01 to 0.50 % by weight.The spice that is present in the chewing gum can be about 0.1 to about 30.0% of chewing gum weight.

Softening agent

But softening agent is joined in the chewing gum to optimize chewiness and the mouthfeel of chewing gum.

Consider that the softening agent that is used for chewing gum comprises glycerol, modified lecithin and its combination.Other edulcorant aqueous solution such as those can be contained Sorbitol, hydrogenated starch hydrolysates, corn syrup and combination thereof as softening agent.

Sweeting agent

Bulk sweetener comprises sugar and sugar-free compositions.Bulk sweetener can consist of 5 chewing gum to about 95 % by weight usually, more generally consists of 20 to about 80 % by weight and the chewing gum that is more typically the 30-60 % by weight.

Sweeting agent plays filler in the chewing gum usually.Sweeting agent improves the juiciness of chewing gum and supports the aromatic property of chewing gum.Sugar sweetener generally includes but is not limited to the usually known saccharic composition that contains of chewing gum field, such as sucrose, glucose, maltose, sugarcane essence, lactose, sorbose, dextrin, trehalose, D-Tag, dried invert sugar, fructose, levulose, galactose, corn syrup solids, glucose syrup, hydrogenated glucose syrups etc. is used alone or in combination.

Sweeting agent can be used in combination with sugar-free sweetener.

Usually, sugar-free sweetener comprises the component with dulcification characteristic, but it lacks usually known sugar and including but not limited to sugar alcohol such as Sorbitol, mannitol, xylitol, hydrogenated starch hydrolysates, maltose alcohol, 3-hydroxy-2-furyl methyl ketone., erythritol, lactose etc., is used alone or in combination.

Depend on concrete sweet taste release profiles and required stability shelf life, bulk sweetener also can be used in combination with high-intensity sweeteners.

Preferred high-intensity sweeteners includes but not limited to sucralose, aspartame, sulfacetamide hydrochlorate, alitame, glucide and salt, cyclohexylsulfamic acid and salt thereof, cyclamate, glycyrrhizin, dihydrochalcone, Talin, Mo Neilin, stevioside etc., is used alone or in combination.For more lasting sweet taste and flavor perception is provided, hope be to form capsule or otherwise control the release that some people is at least made sweeting agent.Can adopt technology as: wet pelletize, wax pelletize, spray drying, spray chilling, fluid bed coat, cohesion (coascervation), the bubble chamber coats and fiber is extruded, to obtain desirable release characteristics.Encapsulated also available other material such as resin carry out.

The working concentration of artificial sweetener will greatly change and will depend on level and type and cost consideration such as sweeting agent effectiveness, rate of release, the required sweet taste of product, used spice.Therefore the active concentration of artificial sweetener can be 0.02 to about 8% variation.When comprising for encapsulated carrier, the working concentration of encapsulated sweeting agent will be higher pari passu.

The combination of sugar and/or sugar-free sweetener can be used in the chewing gum.

If use in addition the softening agent such as sugar or aldehyde alcohol aqueous solution, then softening agent also can provide extra sweet taste.

If need the low-calorie chewing gum, then can use the filler of low-calorie.The example of low calorie bulking agent comprises polydextrose; Raftilose (oligofructose), Raftilin (inulin); Oligofructose (NutraFlora@); IMOS; Guar gum hydrolyzate (SunFiber@); Or stodgy dextrin (Fibersol).Yet, also can use other low calorie bulking agent.

Spice

Chewing gum core provided herein can contain flavouring agent and flavoring agent, for example comprises the natural and synthetic perfume with the form of natural plant component, quintessence oil, essence, extract, powder, comprises acid and other material that can affect sense of taste curve.The example of liquid and powder perfume comprises that Cortex cocois radicis, coffee, chocolate, Rhizoma et radix valerianae, Fructus Vitis viniferae, Fructus Citri tangerinae, Citrus aurantium Linn., menthol, Radix Glycyrrhizae, camerlsed, honey perfume, Semen arachidis hypogaeae, Semen Juglandis, Fructus anacardii, Semen coryli heterophyllae, Semen Armeniacae Amarum, Fructus Ananadis comosi, Fructus Fragariae Ananssae, Fructus Rubi, tropical fruit (tree), Fructus Pruni pseudocerasi, Cortex Cinnamomi, Mentha arvensis L. syn.M.haplocalyxBrig, Ilicis Purpureae, Herba Menthae Rotundifoliae, Eucalyptus and Herba Menthae, fruit essence are for example from the essence of Fructus Mali pumilae, plough, peach, Fructus Fragariae Ananssae, Fructus Pruni, Fructus Rubi, Fructus Pruni pseudocerasi, Fructus Ananadis comosi and Fructus Pruni salicinae.Quintessence oil comprises Mentha arvensis L. syn.M.haplocalyxBrig, Herba Menthae Rotundifoliae, menthol, Eucalyptus, Oleum Caryophylli, laurel, Fructus Foeniculi, Herba thymi vulgaris, cedar leaves oil, Semen Myristicae and above-mentioned fruit oil (for example Fructus Citri Limoniae, bergamot and Fructus Citri tangerinae).

Chewing gum spice can be cryodesiccated natural flavouring, and preferably it is form or its combination of powder, sheet or piece.Longest dimension according to granule calculates, and granularity can less than 3mm, preferably less than 2mm, be more preferably less than 1mm.Natural perfume material can be wherein, and granularity is that about 3 μ m to 2mm are such as the form of 4 μ m to 1mm.Preferred natural flavouring comprises the seed from fruit such as Fructus Fragariae Ananssae, blackberry and Fructus Rubi.

Also various synthetic perfumes can be used in the chewing gum core of the present invention such as the fruit flavor that mixes.Flavouring agent can use less than those normally used amounts.The desirable intensity that depends on used flavouring agent and/or spice, the consumption of flavouring agent and/or spice can be final products weight 0.01 to about 30% (preferred 0.01 to about 15%).The content of preferred flavouring agent/spice is the 0.2-3 % by weight of total composition weight.

Acidulant

Usually also various acid and fruit flavor are used in combination, wherein various acid for example are adipic acid, succinic acid, Fumaric acid, citric acid, tartaric acid, malic acid, acetic acid, lactic acid, phosphoric acid and 1,3-propanedicarboxylic acid or its salt.They add with the amount of 0.01-10% usually.

Filler

The filler that is applicable to chewing gum comprises magnesium carbonate and calcium carbonate, hone limestone flour and silicates such as magnesium silicate and aluminium silicate, Kaolin and clay, aluminium oxide, silicon oxide, Talcum, and titanium oxide, one-lime phosphate, dicalcium phosphate and tricalcium phosphate, sodium sulfate, cellulosic polymer such as ethyl cellulose, methylcellulose and timber or its mixture.

Talc filler can be used in the chewing gum of the present invention, and it can contact or use acid spice or provide required sour environment with by preventing the artificial sweetener degraded with the reaction of Calcium carbonate filler with acid spice.The particle mean size of calcium carbonate and talc filler is generally about 0.1 micron to about 15 microns.

Function and the list of other optional member such as antioxidant, coloring agent and sense of taste covering agent:

Antioxidant

Coloring agent

Coloring agent and brightening agent can comprise FD﹠amp; C class color lake, fruits and vegetables extract, titanium dioxide and combination thereof.

Sense of taste covering agent

Sense of taste covering agent has improved organ sensation's performance of product.Covering agent comprises sucralose, zinc gluconate, ethyl maltol, glycine, acesulfame potassium (acesulfame-K), aspartame, glucide, fructose, xylitol, spray-dired Radix Glycyrrhizae, glycerrhizine, glucose, gluconic acid sodium salt, glucopyrone, ethyl vanillin, vanillin, often effect and high-potency sweetener and various suitable spice.

Activating agent

Chewing gum of the present invention also can comprise the activating agent outside the nicotine.Treat that the activating agent of uniting use with the present invention can be the material that any hope discharges from chewing gum.If wish pick up speed, the effect that then obtains corresponding to spice, main matter has the limited water miscible material that is usually less than 10g/100ml for those, and it comprises complete water-fast material.Example is medicine, nutrition enhancer, oral cavity composition, agent for stopping smoking, high-potency sweetener, PH regulator etc.

Other example of active component comprises acetaminophen, benzocaine, cinnarizine, menthol, carvone, caffeine, acetic acid chlorhexidine, marezine hydrochlorate, 1,8-eucalyptol, nandrolone, miconazole, mystatine, aspartame, sodium fluoride, nicotine, glucide, cetyl pyridine Chloride, other quarternary ammonium salt compound, vitamin E, vitamin A, vitamin D, glyburide or derivatives thereof, Progesterone, acetylsalicylic acid, dimenhydrinate, marezine, metronidazole, sodium bicarbonate, from the active component of Semen Ginkgo, from the active component of propolis, active component, methadone, Fructus Piperis peppermint oil, salicylamide, hydrocortisone or astemizole from Radix Ginseng.

Be the example of activating agent of nutrition enhancer form for example for having vitamin B2 (riboflavin), B12, folinic acid, nicotinic acid (niacine), anorthite, poorly soluble glycerophosphate, aminoacid, vitamin A. D. E and K are salt and the chemical compound of Nutrition of the mineral that contains calcium, phosphorus, magnesium, ferrum, zinc, copper, iodine, manganese, chromium, selenium, molybdenum, potassium, sodium or cobalt of salt, coordination compound and compound form.

In addition, with reference to country variant authoritative institution such as US code of Federal Regulations, Title 21, the nutrient list that Section 182.5013.1825997 and 182.8013-182.8997 generally acknowledge.

Be used for the example of activating agent of compound form of oral cavity and dental care or treatment for example in conjunction with hydrogen peroxide with can chew process and discharge the chemical compound of urea.

The example of the activating agent of antiseptic form is for example for having limited water miscible guanidine and biguanide (for example acetic acid chlorhexidine) and such as salt and the chemical compound of the material of Types Below: quaternary ammonium compound (nerve amines (ceramine) for example, chloroxylenol, crystal violet, chloramines), aldehyde (for example paraformaldehyde), ground quinoline amine (dequaline) chemical compound, anaflex (polynoxyline), phenol (thymol for example, parachlorophenol, cresol), hexachlorophene, the salicylic acid anilides, triclosan, halogen (iodine, iodine tincture, chloramines, dichlorocyanuric acid salt), alcohol (3, the 4-dybenal, benzylalcohol, phenoxyethanol, phenethanol), further referring to Martindale, The Extra Pharmacopoeia, 28thedition the 28th edition, 547-578 page or leaf; Have limited water miscible slaine, coordination compound and chemical compound, aluminum salt (aluminium potassium sulfate AIK (S04) 2 for example for example, salt, coordination compound and the chemical compound that 12H20), should comprise in addition boron, barium, strontium, ferrum, calcium, zinc (zinc acetate, zinc chloride, zinc gluconate), copper (copper chloride, copper sulfate), lead, silver, magnesium, sodium, potassium, lithium, molybdenum, vanadium; Other component that is used for oral cavity and dental care: for example contain salt, coordination compound and the chemical compound (for example sodium fluoride, sodium monofluorophosphate, amino fluoride, stannous fluoride) of fluorine, phosphate, carbonate and selenium.

Further referring to J.Dent.Res., the 28th volume, the 2nd phase, the 160-171 page or leaf, 1949, wherein mentioned the test compound of wide region.

The example of the activating agent of the reagent form of adjusting oral cavity PH for example comprises: the salt of acceptable acid such as adipic acid, succinic acid, Fumaric acid or its salt or citric acid, tartaric acid, malic acid, acetic acid, lactic acid, phosphoric acid and 1,3-propanedicarboxylic acid, the oxide of acceptable alkali such as carbonate, bicarbonate, phosphate, sulfate or sodium, potassium, ammonium, magnesium or calcium, especially magnesium and calcium.

The example of the activating agent of agent for stopping smoking form for example comprises: nicotine, tobacco powder or silver salt such as silver acetate, Disilver carbonate and silver nitrate.

Other example of activating agent is the medicine of any type.

The example of the activating agent of medicament forms comprises caffeine; salicylic acid; salicylamide and related substances (acetylsalicylic acid; choline salicylate; magnesium salicylate; sodium salicylate); acetaminophen; the salt of pentazocine (pentazocine hydrochlorate and pentazocine lactate); Bu Bennuo phenates hydrochlorate; codeine hydrochlorate and codeine phosphate; morphine and morphine salt (hydrochlorate; sulfate; tartrate); methadone hydrochloride; the salt of ketobemidone and ketobemidone (hydrochlorate); the β blocking agent; (propranolol); calcium antagonist; the verapamil hydrochlorate; nifedipine and at Pharm.Int.; Nov.85; the 267-271 page or leaf; the suitable substance of mentioning among Barney H.Hunter and the Robert L and its salt; Talbert; nitroglycerine; nitroerythrol; strychnine and its salt; lignocaine; tetracaine hydrochloride; the etorphin hydrochlorate; atropine; insulin; enzyme (papain for example; trypsin; amyloglucosidase; glucoseoxidase; streptokinase; streptodornase; glucanase; alpha amylase); polypeptide (oxytocin; gonadorelin; (LH.RH); acetic acid Desmopressin (DDAVP)); the cardilan hydrochlorate; the Ergotamine chemical compound; chloroquine (phosphate; sulfate); isosorbide; desaminooxytocin, heparin.

Other active component comprises β-lupeol, Letigen, Sildenafil citrate and its derivant.

Dental product comprises: Carbami, CPP phosphopeptide caseinate; Chlorhexidine, acetic acid chlorhexidine, chlorination chlorhexidine, CHG, Hexetedine; Strontium chloride, potassium chloride, sodium bicarbonate, sodium carbonate; Fluorine-containing composition, fluoride, sodium fluoride, aluminium fluoride, ammonium fluoride, calcium fluoride, stannous fluoride; Other fluorine-containing composition, ammonium fluosilicate, potassium fluosilicate, prodan, single fluorophosphoric acid ammonium, single calcium monofluorophosphate., single fluorophosphoric acid potassium, sodium monofluorophosphate, oleyl (octadecentyl) ammonium fluoride, stearyl trihydroxyethyl Pn dihydroxy fluoride; Vitamin comprises A, B1, B2, B6, B12, folinic acid, nicotinic acid, pantothenic acid (Pantothensyre), biotin, C, D, E, K.

Mineral comprises calcium, phosphorus, magnesium, ferrum, Native Zinc (zink), copper (Cupper), lod, manganese, chromium, selenium, molybdenum.Other active component comprises: Q10@, enzyme.Natural drug comprises Semen Ginkgo, Rhizoma Zingiberis Recens and fish oil.The invention still further relates to the use antimigraine drug, such as 5-hydroxytryptamine antagonist: sumatriptan, Zolmitriptan, naratriptan, rizatriptan, eletriptan; Anti-nausea pill is such as marezine, cinnarizine, dimenhydrinate, diphenhydramine; Anti-Hay Fever medicine is such as cetirizine, loratadine (Loratidin); Pain relief medication is such as buprenorphine, tramadol; Anti-oral disease medicine is such as Miconazole, amphotericin B, Triamcinolone Acetonide (Triamcinolonaceton); With medicine Cisapid, domperidone, metoclopramide.

The preparation chewing gum

Usually, chewing gum can be made by each chewing gum component is sequentially joined in the commercially available blender known in the art.After Initial Composition is fully mixed, the chewing gum material is discharged from blender, be shaped to desirable form and form lamellar and bar-shaped by cutting formation as passing through calendering, extrude in bulk or be cast into ball.

Usually, can mix composition by at first melting gum base and it being joined in the blender of running.Pigment, activating agent and/or emulsifying agent also can add at this moment.Softening agent such as glycerol also can add with syrup and partially filled agent/sweeting agent at this moment.Then other parts filler/sweeting agent can be added in the blender.Flavoring agent adds with back-page filler/sweeting agent usually.High-intensity sweeteners preferably adds after adding back-page filler and spice.

Fully mixed program spends 5-15 minute usually, but sometimes requires the long mixed time.Those those skilled in the art will appreciate that the many modification that can carry out said procedure.Be included in this US patent application that merges document incorporated by reference 2004/0115305 described one-step method.

The structure of chewing gum

According to the present invention, the form of nicotine chewing gum and shape can be any suitable and to user close friend's structure.Therefore chewing gum core or chewing gum for example can be and be selected from ball, cushion (cushion-shaped) ball, rod, sheet, piece, paste, ball shape, ball and spherical form, but chewing gum is by extruding, compress, roll formation and its core filling liquid and/or any type of solid.

Coating

According to the present invention, the chewing gum unit can comprise about 0.1 outer coatings to about 75 % by weight that is applied on the chewing gum core.Therefore suitable types of coatings comprises hard coatings, film coating and Soft Roll clothing and its any combination of any composition, and wherein said composition comprises that those are generally used for the composition of the coating of chewing gum, medicine and confection.

The preferred outer coatings type of the present invention is hard coatings, and this term is used for sweet tablet and sugar-free (or not containing sugar) coating and its combination on conventional meaning.The purpose of hard coatings is for obtaining sweet, frangible layer, and this is appreciated by client and in addition owing to various reasons are protected the chewing gum core.Providing for the chewing gum core in the canonical process of protectiveness sweet tablet; in suitable coating equipment in sugar production line, process successively the chewing gum core with the aqueous solution of crystallizable sugar such as sucrose or glucose; and depend on the stage that coating reaches, this aqueous solution can contain other functional component such as filler, binding agent, pigment etc.In the context of the invention, sweet tablet can contain other function or reactive compound, comprises flavor compounds and/or pharmaceutical active compounds.

Yet, in chewing gum is produced, can be preferably do not have living dental caries sugar compounds in the alternative coating of preferred crystallizable dulcification chemical compound of living dental caries effect with other.This coating is commonly called sugar-free or does not contain sweet tablet in this area.The present invention does not preferably give birth to dental caries hard coatings material and comprises polyhydric alcohol such as Sorbitol, maltose alcohol, mannitol, xylitol, erithritol, lactose, 3-hydroxy-2-furyl methyl ketone. and Tagatose and be the trehalose of not cariogenic monosaccharide and disaccharide, these polyhydric alcohol by commercial run by respectively hydrogenation D-Glucose, maltose, fructose or levulose, xylose, erythrose, lactose, isomaltulose and D-galactose and obtain.

In the typical hard coatings method that will describe in detail hereinafter, the suspension that will contain crystallizable sugar and/or polyhydric alcohol is applied on the chewing gum core and by air blast and evaporates the water that it contains.This circulation must repeat for several times, and 3-80 time usually, to reach desired expansion.Term " expansion " refers to the increase of product weight or thickness, this be when considering the coating operation with final weight or the thickness of the coated product of start-up phase ratio.According to the present invention, coatings consists of the about 0.1 final chewing gum unit to about 75 % by weight, and for example about 10 to about 60 % by weight, comprise about 15 to about 50 % by weight.

In other useful embodiment, the outer coatings of chewing gum of the present invention unit is the unit of experience film art for coating and one or more auxiliary compounds such as plasticizer, pigment and the opacifier that therefore comprises one or more film forming polymer reagent and choose wantonly.The film coating is the thin coating based on polymer that is applied on any above-mentioned form chewing gum core.The thickness of this coating is usually between 20-100 μ m.

Usually, the film coating is by making the chewing gum core by spraying area, and drying is bonded at the material on the chewing gum core and obtains before accepting the next part coating thereafter, has the atomised droplets of coating material in suitable aqueous or the organic solvent vehicle in the spraying area.Repeat this circulation until finish coating.

In the context of the invention, suitable film coating polymer comprises edible cellulose derivative such as cellulose ether, comprises methylcellulose (MC), hydroxyethyl-cellulose (HEC), hydroxypropyl cellulose (HPC) and hydroxypropyl emthylcellulose (HPMC).Other useful film coating materials is acrylate copolymer and copolymer, for example the mixture of methacrylate amino ester copolymer or cellulose derivative and acrylate copolymer.The film coating polymer that is also referred to as functional polymer is specially the polymer of the release performance that has also changed the chewing gum formulations active component except filming performance.The polymer that this change discharges comprises methacrylate copolymer, ethyl cellulose (EC) and designs and resist the acid stomach environment and also be soluble in duodenal enteric polymer.Rear one group of polymer comprises: Cellacefate (CAP), Opaseal (PVAP), Lac, methacrylic acid copolymer, Cellulose acetotrimellitate (CAT) and HPMC.Be understood that outer membrane coating of the present invention can comprise any combination of above-mentioned film coating polymer.

In other embodiments, the film coatings of chewing gum of the present invention unit comprises and can change the polymer physics performance so that its plasticizer more useful when working with filmogen.Usually, polymer is softer and easier scratches the effect of plasticizer in order to make, because plasticizer molecule inserts the interaction that has also therefore destroyed polymer-polymer between each polymer chain bundle.The most of plasticizer that is used for the film coating is amorphous or has very little degree of crystallinity.In the context of the invention; suitable plasticizer comprises for example Polyethylene Glycol of 200-6000 level of polyhydric alcohol such as glycerol, propylene glycol, Polyethylene Glycol; organic ester such as phthalic acid ester, dibutyl sebacate, citrate and glyceryl triacetate comprise the oil/glyceride of the Oleum Cocois of Oleum Ricini, acetyl group glyceryl monoacetate and fractional distillation.

With due regard to reach the related dissolubility of the possible optimal barrier performance of coating and moisture and the diffusibility of gas from film, select to be used for film forming polymer and the plasticizer of chewing gum outer coatings of the present invention.

The film coating of chewing gum unit also can contain one or more coloring agent or opacifier.Except desirable tone is provided, but this reagent reflected light or formation are to the obstruct of moisture and gas.Suitable coloring agent/opacifier includes organic dye and its color lake, inorganic colourant such as titanium dioxide and natural pigment such as beta-carotene or chlorophyll.

In addition, the film coating can contain one or several auxiliary substances such as spice and wax or saccharide compound such as polydextrose, the dextrin that comprises maltodextrin, lactose, modified starch, protein such as gelatin or zein, plant gum or its any combination.

In a specific embodiments, the chewing gum core is the form of rod, at least simultaneously has the edible film that comprises the film former coating at it, film former is cellulose derivative, modified starch, shallac, Radix Acaciae senegalis, dextrin, gelatin, zein, plant gum, synthetic polymer and its any combination for example, and wax such as Cera Flava, candelilla wax, microwax, paraffin and its combination.

Embodiment

Following embodiment is used for illustrating but does not limit the present invention.

Table 1

Embodiment 1

The preparation gum base

The preparation gum base, gum base comprises following composition:

Elastomer

Elastomer elasticizer

Wax

Softening agent

Filler

Antioxidant

Provided detailed prescription in the table 1.Should be emphasized that several other rubber-based compositions can use within the scope of the present invention.

Elastomer and filler are joined in the mixing tank of being furnished with such as the mixed instrument of the Z-shaped arm of horizontal positioned.With still preheating 15 minutes to about 120 ℃ temperature.Because the mechanism rubber in the still fragments into small pieces and softening.

Elastomer elasticizer is slowly added in the elastomer until mixture becomes even.Then residual elasticity body plasticizer is added in the still and also mix 10-20 minute.Add softening ingredient and mix 20-40 minute until whole mixture becomes evenly.

Then enter mixture in the dish and make its dump temperature from 120 ℃ be cooled to room temperature.

Embodiment 2

Prepare chewing gum by using according to the gum base among the embodiment 1 of table 1 preparation.Use the mixed program of conventional machinery, only use appropriate heating.

Gum base and filler is mixed in the mixing tank of being furnished with such as the mixed instrument of the Z-shaped arm of horizontal positioned.Still has been preheating to about 50 ℃ at the most temperature.

Timetable adds other composition according to the rules when material is even in the still.Nicotine adds in initial half mixed process.

Sheet can be formulated as every 0.1-8mg, the nicotine of preferred 2-4mg.Every of the sheet that is used for estimating comprises the 2mg nicotine.

Chewing gum coats by hard coatings.Coating can be for example according to being disclosed in by applying with reference to the method in the US patent 6,627,234 of incorporating this paper into.

Embodiment 3

Sheet can be formulated as every 0.1-8mg, the nicotine of preferred 2-4mg.Every of the sheet that is used for assessing comprises the 2mg nicotine.

Embodiment 4

Embodiment 5

The release of activating agent in external test embodiment 2-4 and two kinds of commercial products.In vitro tests is carried out (European Pharmacopeia the 4th edition chewing machine, 2.9.25Chewing gum medicated, drug release from), wherein a slice chewing gum is chewed in

interval

0,1,2,3,5,7.5,10,20 and 30 minute in PH is 7.4 phosphate buffer at the appointed time.

The result describes and is explained as follows:

Fig. 1 has described the time dependent release profiles of nicotine chewing gum of two kinds of prior aries.

It should be noted corresponding to the typical smoking time, namely in 5-8 minute time initial and middle discharge lower.With remaining in the middle of discharge the rate of release compare 0-1 minute even lower.

These two kinds of prior art chewing gum PA1 and PA2 all wish to use by about 30 minutes process of chewing.In other words, the process that is accumulated as long-term operation of required nicotine in the user blood.

It should be noted that nicotine chewing gum appears as relatively linear release.

Fig. 2 described 0-5 minute initially chew in the phase release of above-mentioned chewing gum PA1 and PA2 Fig. 1 in predetermined distance when being spaced apart 30 seconds.In other words, a kind of differential map solution to release concentrates on the release within the diagram single sub-time period of release time.According to diagram, the sub-time period of evaluation is 0-1/2 minute, 1/2-1 minute, 1-1 ¹/ ₂Minute, 1 ¹/ ₂-2 minutes, 2-2 ¹/ ₂Minute, 2 ¹/ ₂-3 minutes, 3-3 ¹/ ₂Minute, 3 ¹/ ₂-4 minutes, 4-4 ¹/ ₂Minute and 4 ¹/ ₂-5 minutes.

It should be noted within the time longer than the typical smoking time initial and middle discharge increase slower, although true for the release that is presented among Fig. 1 as if more constant.

Fig. 3 has described initial and middle release that can use three kinds of chewing gum I1, I2 of the present invention and I3.Release or the transfer of chewing gum from the chewing gum to the outside described in the mode identical with the prior art chewing gum of Fig. 2.

Described chewing gum is benefited from the interior initial favourable release of initial 5-8 minute whole material time of smoking.Therefore it should be noted in each sub-time period, discharge from being not less than 2% in namely 30 seconds.In other words, when using chewing gum according to the present invention, the nicotine that can obtain constant basis is transferred in the blood via mucosa.

Being characterized as in the first few minutes of the process of chewing of chewing gum I3 that also have that should note discharges very significantly, thereby is easy to alleviate fast, because can be from beginning most to keep the hyperosmosis for mucosa.

It should be noted that further being characterized as of chewing gum I1 and I2 chewing very constant release in initial 5 minutes.When abideing by when for example relating to the sense of taste problem of nicotine in the mouth, can think that this feature is highly beneficial.

Fig. 3 has described the final curves that obtain when chewing nicotine chewing gum in chewing machine.

According to the present invention, can have the as shown in Figure 3 nicotine chewing gum of performance according to following method step application.

Nicotine chewing gum such as I1, I2 or I3 are offered the human body user.Then human user can be chewed selected nicotine chewing gum and can obtain for alleviating fast of thirsting for via the transfer of mucosa from nicotine chewing gum to user blood by nicotine.

Because applied nicotine chewing gum is characterized as at about 1/2 minute that begins from the described process of chewing to about 2 ¹/ ₂Nicotine shifts from chewing gum with the speed greater than selected threshold value transfer velocity in the minutes, can keep the constant osmotic pressure for mucosa in the longer interlude of the process of chewing.By this way, obtained according to an embodiment of the present invention to alleviate fast.

It should be noted that the chewing gum of using according to the present invention is characterized as the transfer of nicotine from chewing gum and was lower than 2mg in per 30 seconds.That should note for example also has I2 to be characterized as to keep per dosage that never was lower than 4mg in 30 seconds.

Fig. 4 has described in initial about 8 minutes of the process of chewing from the initial of above-mentioned chewing gum PA1, PA2, I1, I2 and I3 and centre release.It should be noted that the fastest release profiles tends to flatten after chewing about 4-5 minute.

The invention still further relates to the following embodiment:

1. alleviate the method that nicotine is thirsted for, described method comprises the steps:

Provide at least a chewing gum that comprises nicotiana alkaloids to user,

By chewing described chewing gum nicotiana alkaloids is transferred to the human body of described user and for described user provides alleviating that nicotine thirsts for from chewing gum,

Described the chewing of described chewing gum comprises the following process of chewing: with greater than the speed of threshold value transfer velocity at about 1/2 minute that begins from the described process of chewing to about 2 ¹/ ₂In the minutes nicotiana alkaloids is shifted out from described chewing gum.

2. according to the method that nicotine is thirsted for that alleviates of embodiment 1, wherein said nicotiana alkaloids comprises nicotine.

3. according to the method that nicotine is thirsted for that alleviates of

embodiment

1 or 2, wherein said transfer velocity refers to that nicotine is transferred to the outside of chewing gum from chewing gum.

According among the embodiment 1-3 each alleviate the method that nicotine is thirsted for, wherein said threshold value transfer velocity at about 1/2 minute that begins from the described process of chewing to about 2 ¹/ ₂The sub-time period inner evaluation of minutes.

According among the embodiment 1-4 each alleviate the method that nicotine is thirsted for, described the chewing of wherein said chewing gum comprises the following process of chewing: begin from the described process of chewing about 2 ¹/ ₂Minute to about 10 minutes, preferably from the described process of chewing begin about 2 ¹/ ₂Minute from described chewing gum, migrate out nicotiana alkaloids with the speed greater than another threshold value transfer velocity to about 5 minutes.

According among the embodiment 1-5 each alleviate the method that nicotine is thirsted for, wherein said threshold value transfer velocity cause being included in chew before nicotiana alkaloids in the described chewing gum at 1/2 minute that begins from the described process of chewing to about 2 ¹/ ₂Discharged at least 2% every 30 seconds in the minutes, preferably at least 2.5%.

According among the embodiment 1-6 each alleviate the method that nicotine is thirsted for, wherein said threshold value transfer velocity cause being included in chew before nicotiana alkaloids in the described chewing gum at about 1/2 minute that begins from the described process of chewing to about 2 ¹/ ₂Discharged at least 3% every 30 seconds in the minutes, preferably at least about 4%.

According among the embodiment 1-7 each alleviate the method that nicotine is thirsted for, wherein said threshold value transfer velocity cause being included in chew before nicotiana alkaloids in the described chewing gum at about 1/2 minute that begins from the described process of chewing to about 2 ¹/ ₂Discharged at least 5% every 30 seconds in the minutes, preferably at least about 6%.

According among the embodiment 1-8 each alleviate the method that nicotine is thirsted for, wherein said threshold value transfer velocity cause being included in chew before in the described chewing gum nicotiana alkaloids begin from the described process of chewing about 2 ¹/ ₂Minute discharged at least 2% every 30 seconds to about 5 minutes, preferably at least 3%.

According among the embodiment 1-9 each alleviate the method that nicotine is thirsted for, wherein said threshold value transfer velocity cause being included in chew before in the described chewing gum nicotiana alkaloids begin from the described process of chewing about 2 ¹/ ₂Minute discharged at least 3% every 30 seconds to about 5 minutes, preferably at least 3.5%.

11. according among the embodiment 1-10 each alleviate the method that nicotine is thirsted for, wherein said threshold value transfer velocity cause being included in chew before nicotiana alkaloids in the described chewing gum to about 10 minutes, discharged at least 4% every 30 seconds at about 5 minutes that begin from the described process of chewing, preferably at least 5%.

12. according among the embodiment 1-11 each alleviate the method that nicotine is thirsted for, wherein said threshold value transfer velocity cause being included in chew before nicotiana alkaloids in the described chewing gum to about 30 second time, discharged at least 2-10% at about 0 second that begins from the described process of chewing, preferably at least 5%.

13. according among the embodiment 1-12 each alleviate the method that nicotine is thirsted for, wherein said threshold value transfer velocity cause being included in chew before nicotiana alkaloids in the described chewing gum at about 0 second that begins from the described process of chewing to about 2 ¹/ ₂Release in the minutes is less than 14%, preferably less than 12%.

14. according among the embodiment 1-13 each alleviate the method that nicotine is thirsted for, wherein said threshold value transfer velocity cause being included in chew before in the described chewing gum nicotiana alkaloids begin from the described process of chewing about 10 be released into to about 30 minutes many 18%, preferably at the most 15%.

15. according among the embodiment 1-14 each alleviate the method that nicotine is thirsted for, wherein said threshold value transfer velocity cause being included in chew before nicotiana alkaloids in the described chewing gum at about 1/2 minute that begins from the described process of chewing to about 2 ¹/ ₂Discharged at least 0.03mg in the minutes every 30 seconds, preferably 0.04mg at least.

16. according among the embodiment 1-15 each alleviate the method that nicotine is thirsted for, wherein said threshold value transfer velocity cause being included in chew before nicotiana alkaloids in the described chewing gum at about 1/2 minute that begins from the described process of chewing to about 2 ¹/ ₂Discharged at least 0.05mg in the minutes every 30 seconds, preferably 0.06mg at least.

17. according among the embodiment 1-16 each alleviate the method that nicotine is thirsted for, wherein said threshold value transfer velocity cause being included in chew before nicotiana alkaloids in the described chewing gum at about 1/2 minute that begins from the described process of chewing to about 2 ¹/ ₂Discharged at least 0.08mg in the minutes every 30 seconds, preferably 0.1mg at least.

18. according among the embodiment 1-17 each alleviate the method that nicotine is thirsted for, wherein said threshold value transfer velocity cause being included in chew before in the described chewing gum nicotiana alkaloids begin from the described process of chewing about 2 ¹/ ₂Discharged at least 0.03mg to about 5 minutes every 30 seconds, preferably 0.04mg at least.

19. according among the embodiment 1-18 each alleviate the method that nicotine is thirsted for, wherein said threshold value transfer velocity cause being included in chew before in the described chewing gum nicotiana alkaloids begin from the described process of chewing about 2 ¹/ ₂Discharged at least 0.05mg minute to about 5 minutes every 30 seconds, preferably 0.06mg at least.

20. according among the embodiment 1-19 each alleviate the method that nicotine is thirsted for, wherein said threshold value transfer velocity cause being included in chew before in the described chewing gum nicotiana alkaloids begin from the described process of chewing about 2 ¹/ ₂Discharged at least 0.08mg minute to about 5 minutes every 30 seconds, preferably 0.1mg at least.

21. according among the embodiment 1-20 each alleviate the method that nicotine is thirsted for, wherein at least the 0.5mg nicotiana alkaloids in initial 10 minutes of the process of chewing or preferably chewing in initial 5-8 minute of process and discharge.

22. according among the embodiment 1-21 each alleviate the method that nicotine is thirsted for, the target nicotiana alkaloids of the different piece of wherein said chewing gum in the constantly different or different time of the process of chewing, shifting.

23. according among the embodiment 1-22 each alleviate the method that nicotine is thirsted for, wherein said chewing gum comprises coating, and wherein said coating comprises nicotiana alkaloids.

24. according among the embodiment 1-23 each alleviate the method that nicotine is thirsted for, wherein said chewing gum comprises substantially hydrophilic polymer.

25. according among the embodiment 1-24 each alleviate the method that nicotine is thirsted for, the variation of transfer velocity is minimized.

26. according among the embodiment 1-25 each alleviate the method that nicotine is thirsted for, wherein said nicotiana alkaloids is included in the ion exchange resin.

27. according among the embodiment 1-26 each alleviate the method that nicotine is thirsted for, wherein said nicotiana alkaloids comprises the salt of nicotine.

28. according among the embodiment 1-27 each alleviate the method that nicotine is thirsted for, wherein said nicotiana alkaloids comprises the nicotine of free form.

29. according among the embodiment 1-28 each alleviate the method that nicotine is thirsted for, wherein with described nicotiana alkaloids buffering.

30. according among the embodiment 1-29 each alleviate the method that nicotine is thirsted for, the wherein said process of chewing is less than 30 minutes, preferably less than 20 minutes.

31. according among the embodiment 1-30 each alleviate the method that nicotine is thirsted for, the wherein said time match of chewing process and the cigarette of enfleuraging.

32. according among the embodiment 1-31 each alleviate the method that nicotine is thirsted for, wherein said chewing gum comprises about 2 polymeric systems to about 99 % by weight, about 0.001 spice and about 2 sweeting agents to about 80 % by weight to about 30 % by weight.

33. according among the embodiment 1-32 each alleviate the method that nicotine is thirsted for, wherein said chewing gum comprises about 0 filler to about 60 % by weight, about 0.001 spice and about 2 sweeting agents to about 80 % by weight to about 30 % by weight.

34. according among the embodiment 1-33 each alleviate the method that nicotine is thirsted for, wherein said chewing gum comprises about 0.001 high-intensity sweeteners and about 0.001 spice to about 30 % by weight to about 3 % by weight.

35. according among the embodiment 1-34 each alleviate the method that nicotine is thirsted for, wherein said polymeric system comprises and accounts for chewing gum weight about 0.1 to about 40%, preferably accounts for the elastomer of chewing gum weight about 2 to about 10%.

36. according among the embodiment 1-35 each alleviate the method that nicotine is thirsted for, wherein said polymeric system comprises and accounts for chewing gum weight about 2 to about 60%, preferably accounts for the elastomer elasticizer of chewing gum weight about 5 to about 30%.

37. according among the embodiment 1-36 each alleviate the method that nicotine is thirsted for, wherein said polymeric system comprises and accounts for chewing gum weight about 0 to about 30%, preferably accounts for the wax of chewing gum weight about 0 to about 15%.

38. according among the embodiment 1-37 each alleviate the method that nicotine is thirsted for, wherein said polymeric system comprises and accounts for chewing gum weight about 2 to about 30%, preferably accounts for the softening agent of chewing gum weight about 5 to about 20%.

39. according among the embodiment 1-38 each alleviate the method that nicotine is thirsted for, wherein said polymeric system comprises and accounts for chewing gum weight about 0 to about 50%, preferably accounts for the filler of chewing gum weight about 0 to about 30%.

40. according among the embodiment 1-39 each alleviate the method that nicotine is thirsted for, wherein said polymeric system comprises and accounts for chewing gum weight about 0 to about 5%, preferably accounts for the antioxidant of chewing gum weight about 0 to about 2%.

41. according among the embodiment 1-40 each alleviate the method that nicotine is thirsted for, wherein chew at least described chewing gum of a slice at every turn.

42. according among the embodiment 1-41 each alleviate the method that nicotine is thirsted for, wherein chew at least two described chewing gum at every turn.

43. according among the embodiment 1-42 each alleviate the method that nicotine is thirsted for, wherein chewed at least described chewing gum of a slice in one day.

44. according among the embodiment 1-43 each alleviate the method that nicotine is thirsted for, wherein when someone thirsts for nicotine, chew at least described chewing gum of a slice.

45. according among the embodiment 1-44 each alleviate the method that nicotine is thirsted for, wherein when someone need to comprise the treatment of nicotiana alkaloids or nicotine, chew at least described chewing gum of a slice.

Claims

1. the chewing gum that is used for tobacco alkaloid releasing,

Wherein said chewing gum comprises about 2 polymeric systems to about 99 % by weight, about 0.001 spice to about 30 % by weight, and about 0.001 high-intensity sweeteners and about 2 sweeting agents to about 80 % by weight to about 3 % by weight,

Wherein said polymeric system comprises the elastomer that accounts for chewing gum weight about 0.1 to about 10%,

Wherein said polymeric system comprises the elastomer elasticizer that accounts for chewing gum weight about 2 to about 30%,

Wherein said elastomer elasticizer is selected from:

The methyl ester of pentaerythritol ester, wood rosin and the Colophonium of pentaerythritol ester, part and complete all hydrogenated wood rosin and the Colophonium of the glyceride of the glyceride of the glyceride of the glyceride of-natural rosin ester such as wood rosin and Colophonium, partial hydrogenation wood rosin and Colophonium, the wood rosin of polymerization and Colophonium, the wood rosin of part two polymerizations and Colophonium, glyceride, wood rosin and the Colophonium of Talloil rosin and part and the complete all hydrogenated methyl ester of wood rosin and Colophonium; With

-derived from the terpene resin of australene, nopinene and/or (R)-4-isopropenyl-1-methyl-1-cyclohexene,

Wherein said polymeric system comprises the wax that accounts for chewing gum weight 0 to 30%, accounts for the softening agent of chewing gum weight 2 to 30%, accounts for the filler of chewing gum weight 0 to 50%, accounts for the antioxidant of chewing gum weight 0 to 5%,

Wherein said nicotiana alkaloids comprises nicotine,

Wherein said nicotiana alkaloids is included in the ion exchange resin,

Wherein described nicotiana alkaloids is processed with buffer agent, and

Wherein, in chewing described chewing gum process, the nicotiana alkaloids before chewing in the described chewing gum at 1/2 minute that begins from the described process of chewing to about 2 ¹/ ₂Discharged at least 2% every 30 seconds in the minutes, above-mentioned release data are the regulations according to the 4th edition 2.9.25 of European Pharmacopoeia, and the phosphate buffer of utilizing pH 7.4 is carried out in-vitro measurements and obtained chewing machine.

2. the chewing gum that is used for tobacco alkaloid releasing,

Wherein said nicotiana alkaloids comprises nicotine,

Wherein said nicotiana alkaloids is Andrea Pollack phosphorus nicotine,

Wherein described nicotiana alkaloids is processed with buffer agent, and

3. according to claim 1 chewing gum, wherein said nicotiana alkaloids is Andrea Pollack phosphorus nicotine.

4. each chewing gum according to claim 1-3, wherein said chewing gum are the compacting chewing gum tablets.

5. each chewing gum according to claim 1-3, wherein before chewing the nicotiana alkaloids in the described chewing gum at 1/2 minute that begins from the described process of chewing to about 2 ¹/ ₂Discharged at least 2.5% every 30 seconds in the minutes.

6. each chewing gum according to claim 1-3, wherein before chewing the nicotiana alkaloids in the described chewing gum at about 1/2 minute that begins from the described process of chewing to about 2 ¹/ ₂Discharged at least 3% every 30 seconds in the minutes.

7. each chewing gum according to claim 1-3, wherein before chewing the nicotiana alkaloids in the described chewing gum at about 1/2 minute that begins from the described process of chewing to about 2 ¹/ ₂Discharged at least 5% every 30 seconds in the minutes.

8. each chewing gum according to claim 1-3, wherein before chewing the nicotiana alkaloids in the described chewing gum begin from the described process of chewing about 2 ¹/ ₂Minute discharged at least 2% every 30 seconds to about 5 minutes.

9. each chewing gum according to claim 1-3, wherein before chewing the nicotiana alkaloids in the described chewing gum begin from the described process of chewing about 2 ¹/ ₂Minute discharged at least 3% every 30 seconds to about 5 minutes.

10. each chewing gum according to claim 1-3, wherein the nicotiana alkaloids in the described chewing gum discharged at least 4% every 30 seconds at about 5 minutes that begin from the described process of chewing to about 10 minutes before chewing.

11. each chewing gum according to claim 1-3, wherein the nicotiana alkaloids in the described chewing gum discharged at least 2-10% at about 0 second that begins from the described process of chewing to about 30 second time before chewing.

12. each chewing gum according to claim 1-3, wherein before chewing the nicotiana alkaloids in the described chewing gum at about 0 second that begins from the described process of chewing to about 2 ¹/ ₂Release in the minutes is less than 14%.

13. each chewing gum according to claim 1-3, wherein the nicotiana alkaloids in the described chewing gum about 10 is released into many 18% to about 30 minutes what begin from the described process of chewing before chewing.

14. each chewing gum according to claim 1-3, wherein before chewing the nicotiana alkaloids in the described chewing gum at about 1/2 minute that begins from the described process of chewing to about 2 ¹/ ₂The interior at least 0.03mg that discharged every 30 seconds of minutes.

15. each chewing gum according to claim 1-3, wherein before chewing the nicotiana alkaloids in the described chewing gum at about 1/2 minute that begins from the described process of chewing to about 2 ¹/ ₂The interior at least 0.05mg that discharged every 30 seconds of minutes.

16. each chewing gum according to claim 1-3, wherein before chewing the nicotiana alkaloids in the described chewing gum at about 1/2 minute that begins from the described process of chewing to about 2 ¹/ ₂The interior at least 0.08mg that discharged every 30 seconds of minutes.

17. each chewing gum according to claim 1-3, wherein before chewing the nicotiana alkaloids in the described chewing gum begin from the described process of chewing about 2 ¹/ ₂To the interior at least 0.03mg that discharged every 30 seconds of about 5 minutes.

18. each chewing gum according to claim 1-3, wherein before chewing the nicotiana alkaloids in the described chewing gum begin from the described process of chewing about 2 ¹/ ₂Discharged at least 0.05mg minute to about 5 minutes every 30 seconds.

19. each chewing gum according to claim 1-3, wherein before chewing the nicotiana alkaloids in the described chewing gum begin from the described process of chewing about 2 ¹/ ₂Discharged at least 0.08mg minute to about 5 minutes every 30 seconds.

20. each chewing gum according to claim 1-3, wherein the 0.5mg nicotiana alkaloids discharges in initial 10 minutes of the process of chewing at least, or preferred release in initial 5-8 minute of the process of chewing.

21. each chewing gum according to claim 1-3, wherein said chewing gum comprises coating, and wherein said coating comprises nicotiana alkaloids.

22. each chewing gum according to claim 1-3, wherein said chewing gum comprises substantially hydrophilic polymer.

23. each chewing gum according to claim 1-3, wherein said nicotiana alkaloids comprises the salt of nicotine.

24. each chewing gum according to claim 1-3, wherein said nicotiana alkaloids comprises the nicotine of free form.

25. each chewing gum according to claim 1-3, wherein said polymeric system comprise the elastomer that accounts for chewing gum weight about 2 to about 10%.

26. each chewing gum according to claim 1-3, wherein said polymeric system comprise the elastomer elasticizer that accounts for chewing gum weight about 5 to about 30%.