Composition, promoting smoking cessation, the method of reducing the need for tobacco smoking (options), how to replace tobacco smoking (options)
(57) Abstract:Composition for introduction into the nose includes a solution of nicotine or its pharmaceutically acceptable salt in the pharmaceutical solvent and the agent that creates a viscosity in the range from 1 to 99 CP. The composition has a concentration of nicotine in the range from 10 to 40 mg/ml. Way to reduce human needs in tobacco Smoking and the way to replace tobacco Smoking includes introduction to the nose of the effective dose of the composition. The new nikotinsoderzhaschie composition avoids harmful effects on the smoker carcinogens and carbon monoxide in tobacco smoke and undesirable side effects from Smoking tobacco in relation to other people. Nikotinsoderzhaschie composition is used without disturbing the productive work of the smoker. 5 C. and 17 C.p. f-crystals, 1 Il. This invention relates to compositions and methods used to people who want to quit tobacco or find a socially acceptable substitute for the habit.Because of the known harms associated with tobacco Smoking, but also because of the modern social relations to this problem, leading to increasing the number of places where you do not smoke, smokers, Outi more acceptable social alternative to this habit.For those who are not able to opt out completely from the area, have been proposed various kinds nicotinamidase therapy.Commercially available is nikotinsoderzhaschie chewing gum and are satisfactory for some people, substitutes, substitutes Smoking tobacco. For many people, nicotine gum is not an alternative to a strong desire to smoke because of the gradually achieved and low levels of nicotine in the blood. Many people experience unpleasant side effects such as nausea and indigestion (Jarvis and others, British Medical Journal, I. 285, page 537 (1982); Schneider, Comprehensive Therapy, T. 13, page 32 (1987)).About nikotinsoderzhaschie drops in the nose it was reported in the work Rassell and others, British Medical Journal, I. 286, page 683 (1983) (Jarvis and others, British J. of Addiction, T. 82, page 983 (1987)). However, the reception nasal drip is difficult and uncomfortable at work or in other public places. When using nikotinsoderzhaschie nasal drip can also be observed local nasal irritation. The difficulty in this method is also the unpredictability of the dose received nicotine.It was also reported about the skin patch for transdermal intake of nicotine (Rose, in the Pharmacologic Treatment of Tobacco Dependence, (1986), pages 158-what is slow and can be broken skin blood flow.In U.S. patent N 4920989 and 4953572 described the use of inhaled nikotinsoderzhaschie aerosol, sometimes in combination with nicotine skin patches, as a means of reducing the demand for tobacco Smoking. When using skin patches transdermal absorption of nicotine gives the levels of nicotine in the blood, comparable to the levels obtained when Smoking tobacco. Use one of the nicotine aerosol delivers in the blood significantly less nicotine compared to tobacco Smoking, but irritating to the respiratory system of those who use it, simulating thus the feelings associated with Smoking tobacco.In order to ensure greater penetration of droplets nikotinsoderzhaschie solution in the respiratory route inhalation through the mouth when the simulation area than the deposition in the oral cavity, the size of the aerosol droplets should be 10 microns or less.Although a certain degree of irritation of the respiratory tract is desirable to simulate Smoking, this process is difficult to manage and irritation can be significant, making unwanted use nikotinsoderzhaschie aerosol.Parkins and others (Behavior, Reserch Method, Instruments and Computers (1986), T. 18, page 420 and Psyhopharm. (1989), I. 97, page 529) Ogadenia testing with the introduction of controlled amounts of nicotine to study the physiological actions of nicotine. In these conditions, the subjects were injected with a dilute solution of nicotine taken in several doses for delivery of 1.8 ml over a period of time of 5 minutes for those in the rest of the people, but were not investigated practical nicotine products for everyday use, such that you require to impact against Smoking or as substances that replace Smoking tobacco.U.S. patent N 4579858 describes nicotinamidase the preparation of high viscosity, which is injected into the nose in the form of a viscous tampon. The surface area of such a pad which is in contact with the nasal mucosa, is limited and this is reflected in relatively low levels of nicotine achieved with this method of taking nicotine.There is a need to create a nicotine product suitable as a substitute for tobacco Smoking, which could be used in a public place.The proposed composition for nasal reception, reducing human needs in Smoking tobacco, or as a substitute for tobacco Smoking, including nicotine solution or its pharmaceutically acceptable salt in a pharmaceutically acceptable solvent, with an appropriate agent to provide a viscosity of the composition from about 1 to 99 CP.The invention is described by way of examples, which illustrate the preferred embodiments, with reference to the drawing, which shows the level of nicotine in the blood at various time intervals after administration nikotinsoderzhaschie composition.This invention offers a cost effective alternative to tobacco Smoking by appointment of a person effective dose of nicotine via nasal injection spray.Also proposed nikotinsoderzhaschie composition and nasal sprays suitable for nasal administration.Alternative to Smoking, proposed by this invention can be used as a help when trying to stop Smoking tobacco, but can also be used independently, as a substitute of tobacco Smoking that allows you to avoid unwanted side effects from Smoking tobacco in relation to other people in the vicinity of the Smoking and the harmful effects on the smoker substances such as cancerogene and carbon monoxide in tobacco smoke. Nikotinsoderzhaschie composition and the dispensers of the present invention can be used without disrupting productive work, who uses them, or other normal activities. - Christ.to aromatise directly by the blood stream. If in accordance with this method must be received by the substitute area should be used and absorbed a sufficient amount of nicotine in order to ensure the rapid increase in nicotine in the blood, compared with the same period, achieved when Smoking tobacco, in order to resolve the strong desire of Smoking. Previously suggested substitutes of the area were unsuccessful in this regard because of too small or too slow increase the level of nicotine in the blood.Preferably, nasal intake of nicotine provided sufficient dose of nicotine at a sufficiently large area of nasal mucosa to ensure a rapid increase in the level of nicotine in the blood, without giving locally such a high concentration that would cause irritation of the mucous membrane, and not supplying such a large number nikotinsoderzhaschie compositions that part of the dose flowed from the nose, creating discomfort and irritation receiving the drug.In accordance with the invention, the nicotine or the pharmaceutically acceptable salt of nicotine dissolved in a pharmaceutically acceptable solvent, such as phosphate-buffered saline rest asarnow mucosa. Preferred is a pH of about 5.8.Pharmaceutically acceptable salts of nicotine are known to specialists in this field and include nicotine tartrate and nicotine hydrotartrate.Specialist and other known pharmaceutically acceptable buffering agents.In order to increase the residence time nikotinsoderzhaschie compositions of the invention in the nose, add the appropriate agents to create a viscosity in the range from about 1 to 99 CP. Preferred is the range of viscosity from 10 to 20 centipoise.As is known to the specialist, to create the desired viscosity can be used a large number of agents, including cellulose, substituted cellulose, such as methylcellulose, gumarabic and polyethylene glycol. The desired viscosity can be achieved when using an oil emulsion, an oil phase which is the right oil for nasal welcome, including, for example, lanolin or beeswax. Any agent used to increase the viscosity, of course, be pharmaceutically acceptable and should be well tolerated by the mucous membrane.Nikotinsoderzhaschie composition dankogai minimum number of inhaling nicotine composition Airways located outside of the nose.Research conducted by Yu and researcher. (J. Pharm.Sci., so 73, page 344 (1984) showed that the size of the droplets introduced into the nose or inhaled through the mouth depends on the placement of the droplets. These authors showed that inhalation of droplets ranging in size from 2 to 6 microns, mainly reach the end of the bronchi and alveoli, while a large portion of droplets larger than 10 microns is required for local delivery in the nose.Nikotinsoderzhaschie composition of the invention can be delivered into the nose using any suitable nozzle or spray device, which performs the spray droplets larger than 10 microns. For example, there can be used conventional spray-type nozzles, which are used for nasal protivozastojnye drug or device for measuring the dose spray, such as used for nasal steroid applications. These devices produce 98% of droplets with a diameter greater than 16 microns, and the majority of the droplets have a size of approximately 100 to 200 microns. As it is clear to the specialist, the viscosity of the composition of the invention should be optimized depending on the type used spray ustroystva the composition should have a viscosity of not more than 10 centipoise. When using the device type of meter dose spray can be used in composition with a viscosity of 30 centipoise with a good education droplets, with the increase in viscosity above this value there is a tendency to the formation of rather fluid flow than aerosol. A specialist can easily be determined a suitable viscosity of the composition for a specific type of spray device.When performing a nasal spray composition of the invention nicotine is not involved in the respiratory tract, located next to the nose, and, thus, avoids irritation of the respiratory tract and is allowed the use of higher concentrations of nicotine that allows you to raise the levels of nicotine in the blood to appropriate indicators, comparable to Smoking without the associated irritation.Expert it is clear that the concentration of nicotine in the composition of the invention and the scope of the composition introduced into the nose can vary to create a person the necessary dose of nicotine. Supply volume should be selected so that it is good to keep in the nose, not emerging. The concentration of nicotine should be of such importance, to prevent unacceptable matnog is Britania can be used in the amount of approximately from 0.03 to 0.08 ml per nostril with good retention of the composition in the nose. When used in accordance with this invention, the nasal mucosa is well tolerated concentration of nicotine in the range from about 10 to 40 mg/mlIn order to roughly estimate the dose of nicotine delivered in the blood of a smoker when Smoking one cigarette, i.e., approximately 1 mg (Russel and researcher. above), the nose must be delivered to 2 mg of nicotine. If, for example, used jet device, which supplies about 0,03 ml nicotine composition for one compression, and the composition has a concentration of 20 mg/ml of nicotine, one compression delivers 0.06 mg nicotine, and triple application will deliver approximately 2 mg of nicotine.In accordance with the proposed embodiment of the invention uses a composition having a viscosity of about 10 centipoise with the concentration of nicotine of about 20 mg/ml dissolved in phosphate buffer saline with a pH of about 5.8. The composition is introduced into the nose using a spray device, which supplies about 0,03 ml of a composition per one operation of the device in the form of nepalaya jets, droplets having a diameter of at least 10 microns.Nicotine composition of the invention may also, optionally, contain one or more as ascorbic acid. Specialist known corrigentov and preservatives that are acceptable for food use in the pharmaceutical industry, and suitable concentrations of these agents.Application nikotinsoderzhaschie compositions of the invention, in the form of a nasal spray in accordance with this invention showed good tolerability person with minimal side effects in the form of light and temporary nasal flow.Application nikotinsoderzhaschie nasal spray in accordance with the invention, it is found that allows the smoker to effectively perform their duties in a non-Smoking environment at least for three years without a return of symptoms or a strong desire to smoke tobacco.The following examples are only to illustrate the invention and does not limit it.Example 1.Nicotine (98-100% free base, catalogue N 3876, Sigma Chemical Co. St. Zouis, Mo) was dissolved in phosphate-buffered saline (FBI: 0,175 g Na2HPO4/100 ml; 1,21 g NaH2PO4/100 ml; 0,292 NaCl/100 ml) with the formation of concentrations of nicotine (20 mg/ml of This solution had a pH of 5.8 and osmotic pressure of 290 mOsm. Then added carboxymethylcellulose, giving in is whether the spray nozzle type.The atomizer was used for the introduction of 2.4 mg nicotine man in the nose for 5 seconds by means of four compression sprayer (two compression in each nostril). The blood samples of the subjects were selected from protivoluchevoi veins of the hands at different time intervals after administration of nicotine (zero time in the drawing), and the concentration of nicotine in the blood was determined by the method Feyerband and Russell (J. Pharm. Pharmacol, T. 32, pp. 178-181 (1980)). The results are shown in the drawing.The achieved results concentrations of nicotine in the blood were similar to those results obtained by Smoking cigarettes, and the limit value was reached after approximately 15 minutes after administration, only a little later than after Smoking cigarettes.Despite the fact that have been described and illustrated only the preferred embodiment, the invention is not limited to the signs of these embodiments, but includes all variations and modifications within the scope of the claims. 1. Composition, contributing to the reduction of human needs in the Smoking of tobacco or a tobacco substitute comprising a solution of nicotine or its pharmaceutically acceptable salt in a pharmaceutical solvent, characterized in that Concentratio nicotine in the range of 10 - 40 mg/ml2. The composition according to p. 1, characterized in that the pharmaceutical solvent is a phosphate-saline.3. The composition according to p. 2, characterized in that said agent that creates the viscosity is cellulose or a substituted cellulose.4. The composition according to p. 3, characterized in that said agent that creates the viscosity is carboxymethylcellulose.5. The composition according to p. 2, characterized in that said agent that creates the viscosity is pharmaceutically acceptable oil emulsion.6. The composition according to p. 2, characterized in that its pH is in the range of 5 to 7.5.7. The composition according to p. 2, characterized in that its pH is in the range of 5 to 6.5.8. The composition according to p. 2, characterized in that its pH is about 5.8, the concentration of nicotine corresponds to 20 mg/ml, and the composition contains carboxymethylcellulose to create a viscosity in the range of 5 - 20 SP.9. Composition according to any one of paragraphs.1 to 8, characterized in that it presents in the form nikotinsoderzhaschie sprayable solution containing droplets with a size suitable for delivery in the nose.10. The composition according to p. 9, characterized in that, these droplets have a size of 100 to 200 microns in diameter.12. Composition according to any one of paragraphs.1 to 8, characterized in that it is a spray device suitable for delivery to the nose of the effective dose of the composition in the form of droplets with a size selected in this range, which is useful for delivery of drops in the nose.13. Composition according to any one of paragraphs.1 to 8, characterized in that it is a spray device suitable for delivery to the nose of the effective dose of the composition in the form of droplets with a size diameter of at least 10 MK.14. Composition according to any one of paragraphs.1 to 8, characterized in that it additionally includes one or more corrigentov, preservative agent and antioxidant.15. Way, contributing to the reduction of human needs in the Smoking of tobacco, including the introduction nikotinsoderzhaschie composition, characterized in that it includes an introduction to the nose of the effective dose of a composition according to any one of paragraphs.1 - 8.16. The method according to p. 15, characterized in that it includes an introduction to the nose of the composition according to any one of paragraphs.1 to 8 in number, which delivers a dose of nicotine 1 to 3 mg.17. Way, contributing to the reduction of human needs in Smoking tobacco, on the eskers of the spray solution on p. 9 or 10.18. The method according to p. 17, characterized in that it includes an introduction to the nose nikotinsoderzhaschie spray solution on p. 9 or 10 in number, which delivers a dose of nicotine 1 to 3 mg.19. How to replace tobacco Smoking, including the introduction nikotinsoderzhaschie composition, characterized in that it includes an introduction to the nose of the effective dose of a composition according to any one of paragraphs.1 - 8.20. The method according to p. 19, characterized in that it includes an introduction to the nose of the composition according to any one of paragraphs.1 to 8 in number, which delivers a dose of nicotine in the range of 1 to 3 mg.21. How to replace tobacco Smoking, including the introduction nikotinsoderzhaschie solution, characterized in that it includes an introduction to the nose of the effective dose of the spray solution on PP.9 and 10.22. The method according to p. 21, characterized in that it includes an introduction to the nose nikotinsoderzhaschie spray solution on p. 9 or 10 in number, which delivers a dose of nicotine in the range of 1 - 3 mg
FIELD: pharmaceutical industry.
SUBSTANCE: invention is characterized by that system contains underlayer, therapeutical substance storage layer, and agent attaching the system on the person's skin and allowing access of nicotine to skin. System is transparent (opacity factor below 48.6%).
EFFECT: facilitated transcutaneous transport of nicotine.
8 cl, 1 tbl
SUBSTANCE: method involves recording arterial blood pressure, heart beat rate, respiration frequency, sublingual body temperature and rectal body temperature. The measurements are repeated 3, 5, 7, 9, 11, 13, 15, 20 min later after introducing xanthinol niacinate. Difference of maximum and minimum values of each factor is calculated, respectively. Parasympathetic patient responses predominance is determined from calculated values.
EFFECT: high accuracy in determining organism tolerance to reactive vasoconstriction.
2 cl, 4 tbl
FIELD: medicine, narcology, pharmacy.
SUBSTANCE: invention relates to nicotine-containing preparations possessing prolonged stimulating effect and used in loss the smoking habit. The preparation is prepared by a method involving preparing a gel-base by addition of 2.5-3.0% gel of hydroxypropylcellulose in ethanol to 10-13% ethanol solution of copolymer of N-vinylpyrrolidone with organic unsaturated acid ester in the mass ratio copolymer of N-vinylpyrrolidone with organic unsaturated acid ester : hydroxypropylcellulose in gel-base = (7.0-1):(7.5-1). Then cetyl alcohol, isopropyl myristate, propylene glycol, preliminary melted stearic acid, colloidal silicon dioxide and nicotine are added successively to the prepared gel-base at constant stirring and temperature 30-35°C. Invention provides enhancing the prolonged effect of the preparation.
EFFECT: improved preparing method, enhanced and valuable properties of preparation.
3 cl, 1 tbl, 2 ex
SUBSTANCE: method involves delivering nicotine to patient organism and administering medicament by smearing internal surface of superior and inferior nasal passage part. Treatment is carried out with cigarette consumption being retained. Smell receptor canal blocker like rapid sodium canal blocker lidocaine is used as the medicament. Its aerosol is introduced immediately before smoking action as single jet in each nasal passage. Medicament introduction is localized with epithelial smell receptor cells arrangement.
EFFECT: enhanced effectiveness of treatment.
2 cl, 2 tbl
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to the development of medicines used for enhancing resistance of humans and animals to hypothermia. Agent for enhancing resistance of humans and animals to hypothermia comprises nicotinic acid, glutamic acid, riboflavin, ascorbic acid, uniquinone, succinic acid, polyethylene oxide and water taken in the definite ratio. Also, invention proposes a method for enhancing resistance of humans and animals to hypothermia involving administration of the abovementioned agent 30 min before works associated with hypothermia and after its termination for activation of vital essential biochemical processes. Invention provides enhancing resistance to overcooling under extreme conditions and using in surgery practice in cooling organs (in operations in heart and brain).
EFFECT: enhanced effectiveness and valuable medicinal properties of agent.
2 cl, 2 tbl, 1 dwg, 2 ex
FIELD: medicine, vitamins.
SUBSTANCE: invention proposes a composition of vitamins riboflavin and nicotinic acid (niacin) or nicotinamide for treatment of primary headaches representing usual migraine, classic migraine, migraine combined with "histamine" headache. The composition comprises the combination of 0.5-750 mg of nicotinic acid (niacin or nicotinamide) and 0.1-250 mg of riboflavin. Also, the invention involves the corresponding method for treatment. Proposed treatment provides body with necessary NAD/NADP and FAD/FMN in order to modulate activity of mast cells when changes in their secretion results to migraine. Method provides disappearance of all migraine symptoms during the next 20 months of dispensary observation.
EFFECT: enhanced medicinal effectiveness of vitamins.
SUBSTANCE: invention proposes a liquid pharmaceutical composition containing nicotine in any form for administration into the mouth cavity and alkalinized with a buffer and/or by regulation of pH value. Administration is carried out preferably by spraying and the most preferably by sublingual spraying. Also, invention relates to a method for preparing the indicated composition. Use of indicated composition in therapy, such as therapy for treatment of addiction to tobacco.
EFFECT: valuable pharmaceutical properties of composition.
51 cl, 11 ex