Oh, patents! Oral transmucosal NRTs

Copyright © Françoise Herrmann

 

Ok, May 31, 2014 – UN World No Smoking Day,  minus 36 hours! Or, what you really want, without the pain of withdrawal…!

Nicotine replacement therapies (NRTs) are recommended by the NIH (National Institutes of Health), the ACS (American Cancer Society) and the ALS (American Lung Association) as first line approaches to smoking cessation. NRTs  include patches, lozenges, sprays and gum. (See a previous post on .. for Transdermal nicotine patches). Research indicates that NRTs in association with counseling double your chances or quitting (Pierce et. al, 2012)

 If your Doctor skipped town, or has already given up on you… then you can always go to Walgreens to pick up some nicotine gum or lozenges, marketed under the brand name Nicorette®, one of the first FDA-approved NRTs.

 

Nicotine gum marketed as Nicorette®  uses a “park and chew” technology. Using the “park and chew” technology, a consumer “bites” on the gum to release nicotine, and then “parks” the gum inside their cheek, and then ”bites” again when more nicotine is needed. This prevents excess nicotine release, and the ensuing undesirable side effects such as dizziness, nausea or stomach problems.

The original (and expired) Nicorette® nicotine replacement patents from the 1970s are US3877468 titled Chewable tobacco substitute composition, disclosing “Chewable smoking substitute composition comprises at least about 40 percent by weight of a gum base and a tobacco alkaloid dispersed in said gum base in an amount sufficient to provide smoking satisfaction.”; US3901248 titled Chewable smoking substitute composition and US3845217 titled Buffered smoking substitute compositions. More recent Nicorette® patents include the nicotine lozenge patent  US2011110880 titled Nicotine Lozenge compositions, and  a flavoring patent,  US2006275344 titled Flavoring of drug-containing chewing gum.

Incidentally, nicotine gum is  a very patented product! The EPO returned 184 patents for a search on “nicotine gum”. There are in fact many different sorts of nicotine gums, that is, different formulations of the gum base and of the non-toxic active nicotine ingredient; different oral transmucosal delivery systems or release technologies for the nicotine in the gum; and different flavors that may be added to the gum to make it palatable or compatible with release of the active ingredient.

Here is an additional short list of the nicotine gum patents:

• US2014099269 Chewing gum having sustained release of nicotine
• US2013323184 Method of providing fast relief to a user of nicotine chewing gum
• US2012039981 Coated nicotine-containing chewing gum, manufacture and use thereof
• WO2013059592 Excipients for nicotine containing therapeutic compositions
• WO2014091631 Method of releasing nicotine from chewing gum
• US6344222B1 Nicotine, hydrophilic and hydrophobic polymer, buffer time-release agents (to improve release rates of nicotine)
• US8658200 Flavoring of drug-containing chewing-gums

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Finally, here is a cessation quote to ponder:

“Nicotine is an addictive poisonous alkaloid C₅H₄NC₄H₇NCH₃, derived from the tobacco plant. Nicotine is also used as an insecticide. Approximately 40 milligrams* of nicotine is able to kill an adult (Merck Index).” (Extracted from US2006275344)

 *40 mg = 1 US teaspoon 

Reference

John P. Pierce, Sharon E. Cummins, Martha M. White, Aimee Humphrey, and Karen Messer (2012)

Quitlines and nicotine replacement for smoking cessation: Do we need to change policy? Annual Review of Public Health, 33:341-356.
http://www.annualreviews.org/doi/abs/10.1146/annurev-publhealth-031811-124624

Oh, patents! Smokeless blucigs™

Copyright © Françoise Herrmann

In France the verb “fumer” (to smoke) is being replaced with the verb “vapoter” (to vape) in reference to the use of smokeless electronic cigarettes.  And in this case, it follows that the French e-cig smoker becomes a “vapoteur” (+masculine) or “vapoteuse” (+feminine), whereas in English, that would perhaps be a “vaper” or an “e-cig” user.

E-Cigs, and blucigs™ in particular as an example of the marketed product, are electronic cigarettes, rechargeable and purported green, the same size as tobacco cigarettes. They are called “blu” because of their LED tip that lights up blue with every puff (or “vape”). The blucig™ contains a rechargeable battery for the LED light, a cartridge of “smoke juice” (that is a proprietary liquid concoction containing nicotine, but without the 7000 chemicals created when burning tobacco cigarettes such as carbon monoxide, nitrogen oxide, hydrogen cyanide and ammonia), a heating cell for the “smoke juice”, an atomizer that vaporizes the “smoke juice”, and a silicone tip designed to supply the “deeply satisfying resistance” of a puff (or “vape”)!  So, when you inhale or “vape”, the activated battery turns on the blue LED light and heats the “smoke juice”, which is then converted to vapor that is inhaled or “vaped”, providing users or “vapers” with an experience just like smoking a tobacco cigarette, without any of the burning and harmful “smoke”.

The blucig™ cigarette pack design is patented as design patent (USD700994), and the original vaporizing cigarette patent US3200819 titled: “Smokeless non-tobacco cigarette” was filed in 1965.  Interestingly enough,  the original smokeless cigarette invention was “ to provide a safe and harmless means for and method of smoking by replacing burning tobacco and paper with heated, moist, flavored air; or by inhaling warm medication into the lungs in case of a respiratory ailment under direction of a physician”. Thus, the smokeless cigarette was originally designed both as a medicine delivery system and a substitute to tobacco smoking. 

However, it was only at the beginning of the 21^st century that electronic cigarettes were manufactured and brought to the market, via China, where they were patented alternatively as “electronic aerosol cigarettes” (CA2647212 A1), “electronic atomization cigarettes” (CA2562581 A1) and later in the US as “electronic smoking-substitute devices” (US20100031968 A1).

Now, if you intend to quit smoking on May 31 – World No tobacco Day, and have in mind that you might still puff vapor (or vape) on something like electronic cigs, in replacement of the 7000 (yes, seven thousand) chemical compounds created when puffing on a tobacco cigarette, 70 of which are known carcinogens according to the American Lung Association [ALA], you might want to hold off until you hear what the NIH (National Institute of Health) has to say about e-cigs, and exercise caution.

First, according to Kushner et. al (2011) electronic cigarettes are novel nicotine delivery systems, rather than nicotine replacement systems. They are termed ENDS (Electronic Nicotine Delivery Systems) by the WHO (World Health Organization) and there is no data on the safety or efficacy of the “smoke juice” containing aromas and propylene glycol, or the vapors inhaled. Only those E-cigs marketed for therapeutic purposes can be regulated by the FDA Center for Drug Evaluation and Research (CDER). And because there is no data on such items as: potential risks when used as intended;  how much nicotine is being inhaled or other potentially hazardous chemicals; and whether there are associated benefits when using the products,  e-cigs are not approved as a smoking cessation device.

So, in the countdown to May 31, 2014 – World No Tobacco Day, you may want to be cautious about switching to e-cigs (blucigs™ , Premium™ vapes or any other e-cig brand), since the “smoke juice” that is vaporized and inhaled is a complex substance for which there is still no efficacy or safety profile. Indeed, e-cig ad messages display: Don’t quit. Switch., which at best appears to be defeating its own purpose..

On the other hand… there are BUY NOW! Premium™ vapes advertisements on the splash page of the FDA website..! [FDA(2)] So, go figure out the bottom line to the bottom line…!

References

ALA - American Lung Associationhttp://www.lung.org/associations/states/colorado/tobacco/
blucigs™
http://www.blucigs.com/

FDA – Electronic cigarettes

http://www.fda.gov/newsevents/publichealthfocus/ucm172906.htm
FDA (2)

http://fda.org/
Kushner, W. G., Reddy, S. and H.S. Paintal (2011) Electronic cigarettes and third hand tobacco smoke: two emerging health care challenges for the primary care practitioner. International Journal of General Medicine 4: 115-120.

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068875/

Oh, patents! Transdermal nicotine patch

Copyright © Françoise Herrmann

The NIH (National Institutes of Health) NIDA (National Institute on Drug Abuse) suggests one or a combination of three approaches to quit smoking:

1. Behavioral (e.g.; counseling, self-help or the Department of Health 800-QUIT NOW hotline)
2. Nicotine replacement therapies or NRTs (e.g.; nicotine patches, nicotine gum, nasal sprays, inhalers and lozenges), and
3. Medication (e.g.; Zyban, and Chantix which blocks nicotine receptors) [NIH, Drug Facts]

Transdermal nicotine patches thus offer a nicotine replacement approach to quitting. A search for nicotine patches at the EPO yields several different patents. For example:

 

US4920989 and US5016652 both titled:  Method of aiding in reduction of the incidence of tobacco smoking are assigned to the University of California.They disclose transdermal patches for administration of nicotine to the bloodstream. “at a rate sufficient to correspond to the nicotine level in the blood which is achieved by the normal smoking patterns of the individual”; and additionally, a combination nasal aerosol spray (in US4920989) designed:  “to provide desired sensations in the respiratory tract to which the user is accustomed from normal tobacco use.” 

The stated advantage of this form of nicotine replacement therapy, compared to nicotine gum for example, is that it is able to deliver adequate quantities of nicotine in the blood stream, without the displeasing taste of nicotine gum or the gastroinstestinal upset.

The abstract for US4920989 in included below with a patent figure drawing and a commercial figure drawing of the transdermal reservoir patch:

A method of aiding in the reduction of incidence of tobacco smoking. The method comprises applying a patch containing nicotine to the skin of a person with whom smoking reduction is desired and allowing the nicotine to transdermally migrate into the person's bloodstream to achieve a desired systemic nicotine level. The method also comprises the simultaneous administration of a nicotine containing aerosol spray to the oral cavity of the user in order to provide the desired sensations in the respiratory tract to which the user is accustomed from normal tobacco smoke. A combination of the spray and transdermal patch is also provided such that an occlusive patch is applied to the skin of the person with whom smoking reduction is desired and the nicotine containing aerosol spray is delivered to the oral cavity simultaneously with the application of the nicotine from the patch.

There are many other patents related to dosage and/or comfort of transdermal nicotine patch therapy. For example:

US5230896 titled Transdermal nicotine delivery system discloses “a novel transdermal delivery system to satisfy addicted smokers’ cravings” which offers an option to transdermal patches containing a reservoir of the drug.  The novel construction of the patch consists of a nicotine base within an acrylate polymer matrix, so that the patch is neither bulky nor conspicuous when worn.

US5603947 titled Method and device for providing nicotine replacement therapy transdermally/transbucally discloses a patch for heavy smokers which delivers an average flow rate of nicotine that exceeds the prior art delivery amounts.

There are also known disadvantages of the transdermal delivery mode, in general, and in particular for nicotine delivery (Prausnitz & Langer, 2008). For example, one of the known disadvantages is skin irritation that can be caused by the patches. This problem is addressed and patented, for example in US2013053357 titled: Skin irritant suppression and transdermal preparation which discloses delivery of an irritant suppression agent in conjunction with a drug such as nicotine, in a transdermal patch. 

US2009169606 titled Low flexural strength transdermal tobacco alkaloid patch also addresses the issue of patch comfort and the risks of leaking in transdermal reservoir technology by disclosing a patch with a high degree of flexibility (i.e. low flexural strength).

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So… in the countdown to May 31 – World No tobacco day – transdermal nicotine replacement patches appear as one patented option available to assist with cessation. 

References

NIH – Drug Facts: Cigarettes and other tobacco products

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2700785/   
Prausnitz, M. R. & R. Langer (2008) Transdermal delivery
Nat Biotechnology, Nov.2008, 26(11), 1261-1268

http://www.drugabuse.gov/sites/default/files/tobacco12_0.pdf