JP2011111418A - Viral infection-preventing preparation suitable for intra-oral cavity local administration - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a preparation comprising caffeine as an active ingredient, suitable for intra-oral cavity local administration and preventing viral infection, especially influenza viral infection. <P>SOLUTION: This influenza viral infection-preventing preparation includes the caffeine loaded on a carrier suitable to make the active ingredient stay in the oral cavity by the intra-oral local administration. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a virus suitable for local intraoral administration containing caffeine as an active ingredient, particularly a preparation for preventing influenza virus infection.

  Infection routes for influenza A and B, including the new influenza, touched the virus-contaminated "splash infection" where the virus directly invades the surrounding person's respiratory system by sneezing or coughing There are “contact infection” in which the virus enters through the mucous membranes such as eyes, nose and mouth, and “air infection” in which the virus floating in the air enters the same space as the infected person. An effective measure to prevent influenza is to prevent the invasion of viruses from these infection routes.

  Wearing a mask and encouraging gargle is a preventive measure for infection through the oral cavity, but gargles with bactericidal drugs such as povidone iodine and chlorhexidine gluconate are not effective in eradicating influenza viruses and are persistent in the throat It is said that there is a risk of damaging the normal cells of the throat, destroying the bacterial flora, allowing the virus to enter. Chlorhexidine gluconate is also at risk of destroying oral flora. Therefore, it is important that the active ingredient of the preparation for preventing viral infections by topical administration in the oral cavity, such as a mouthwash, has an antiviral action selectively and does not kill the oral bacterial flora.

  It has already been reported that caffeine has an antiviral action against influenza virus (see Non-Patent Document 1), and is a candidate drug for such an active ingredient.

  Caffeine has a strong central nerve stimulating action and is used as a cardiotonic drug, central stimulant, diuretic, migraine analgesic and the like. Because it acts on the cerebral cortex and removes drowsiness, it is prescribed as a cold medicine that contains antihistamines.

  Recently, it has been reported that a combination of statins having an action of lowering LDL cholesterol in blood and caffeine is effective for the treatment and prevention of virus, particularly influenza A and B influenza virus infection (patent) Reference 1).

  Caffeine is prescribed as a therapeutic agent for equine viruses, particularly herpes virus type I infection, in the form of a mixture with potassium iodide and ammonium chloride (see Patent Document 2).

  The use of caffeine as an antiviral agent described so far is intended for systemic administration, including oral, parenteral and nasal administration. On the other hand, a composition for treating herpes simplex virus infection comprising caffeine and an ingredient suitable for local administration, which is locally administered to the surface infection site, is also known (see Patent Document 3).

Prahoveanu, E .; et al, "Effect of caffeine on experimental influenza in mice", Virology, 1985, 36 (1): 37-40. WO2008 / 034832 A1 JP-A-5-112457 Japanese Patent No. 3180221

  However, it is not known to use caffeine as an active ingredient of a preparation suitable for topical administration in the oral cavity for the prevention of influenza virus infection via the oral cavity.

  Accordingly, an object of the present invention is to provide a virus infection-preventing preparation suitable for topical administration in the oral cavity using caffeine as an active ingredient.

  The present invention provides an influenza virus preventive preparation suitable for topical oral administration, comprising caffeine supported on a carrier capable of retaining an active ingredient in the oral cavity by local oral administration.

  Since the effect of caffeine is to suppress virus growth, it is necessary to maintain caffeine in the oral cavity in order to prevent viral infection via the oral cavity. Therefore, in the present invention, the carrier for supporting caffeine according to the dosage form contains a water-soluble polymer (thickening agent) having a thickening action and / or a thickening component.

  The dosage form is a liquid solution such as a mouthwash, a spray for oral cavity, or an effervescent tablet for preparing a mouthwash by dissolving in an appropriate amount of water at the time of use, a troche that gradually releases the active ingredient by containing in the mouth A solid preparation such as a drop. A water-soluble polymer (thickening agent) having a thickening action is added to the solid preparation as a part of the formation, and a thickening component is added to the liquid preparation.

  Such water-soluble polymers include natural polymers such as gelatin, casein, hyaluronic acid, tragacanth gum, xanthan gum, pectin, carrageenan, sodium alginate, glucomannan; methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carmellose sodium And water-soluble synthetic polymers such as povidone, crospovidone, copolydon, polyvinyl alcohol, sodium polyacrylate, and the like.

  The thickening component includes viscous liquids at room temperature such as glycerin, propylene glycol, polyethylene glycol, and polyoxyethylene sorbitan. In the liquid agent, a thickening component and a water-soluble polymer having a thickening action may be used in combination.

  The methods for producing the solid preparations and liquids exemplified above are well known to those skilled in the art. The virus infection-preventing preparation of the present invention can be produced according to a known production method using caffeine as an active ingredient and using a water-soluble polymer and / or a thickening ingredient as a part of the formation. . The solid preparation can contain conventional additives such as excipients such as starch, saccharides and sugar alcohol, lubricants, effervescent agents in the case of effervescent tablets, and preservatives in the case of liquids.

  Hereinafter, the present invention will be described in more detail with some formulation examples.

[Example 1] Gargle (effervescent tablet)
The manufacturing method is as follows.
1 kg of caffeine, 0.4 kg of povidone K30, 1 kg of dry magnesium bicarbonate, 1 kg of anhydrous citric acid, 0.76 kg of lactose, 0.2 kg of carmellose, 0.04 kg of magnesium stearate, and a small amount of mint oil are mixed and dried. Effervescent tablets are prepared according to the method.
Dissolve one tablet in 50 mL of water at a time and gargle. Do this several times a day.

[Example 2] Gargle (Liquid)
The manufacturing method is as follows.
0.05 g of mint oil is mixed with 8 g of polyoxyethylene hydrogenated castor oil. To this, 10 g of D-sorbitol, 200 g of glycerin, 100 g of macrogol 400 and 300 g of purified water are mixed and stirred, and then 2 g of caffeine is added and heated to about 60 ° C. to dissolve. Make 1 L with purified water after cooling.
Take 50 mL once and gargle. Do this several times a day.

[Example 3] A method for producing a spray for oral cavity is as follows.
1 g of caffeine is dissolved in 40 mL of purified water. 1 g of gelatin and 6 g of povidone K30 are added to this and heated to about 60 ° C. to dissolve. After cooling, add 45 g of concentrated glycerin and a small amount of 1-menthol, and make up to 100 mL with purified water. Fill this into a spray container with a nozzle.
Spray directly on throat. Spray several times a day.

[Example 4] A method for producing an oral spray is as follows.
1 g of caffeine is dissolved in 40 mL of purified water. To this, 1 g of pectin, 1 g of carrageenan and 8 g of povidone K25 are added and heated to about 60 ° C. to dissolve. After cooling, add 40 g of concentrated glycerin and a small amount of l-menthol, and make up to 100 mL with purified water. Fill this into a spray container with a nozzle.
Spray directly on throat. Spray several times a day.

[Example 5] Oral tablet (drop agent)
The manufacturing method is as follows.
Caffeine 25g, Hydroxypropylcellulose 250g, Gelatin 225g, Sucrose 1000g, Mizuame 500g are charged into an aluminum pan and heated in a direct flame method while adding an appropriate amount of purified water and kneaded. When the heat is reduced, add a small amount of cacao, stir well, spill into the laver and cool down to the proper temperature, and then pass through the drop machine.
Melt or chew one by one in the mouth. Up to two at a time, up to three times a day.

Claims (6)

An influenza virus infection-preventing preparation comprising caffeine carried on a carrier suitable for retaining an active ingredient in the oral cavity by local administration in the oral cavity.   The dosage form is a gargle, a solid preparation for preparing a gargle by dissolving in an appropriate amount of water at the time of use, an oral spray, or a solid preparation that gradually releases active ingredients by saliva when contained in the mouth 1. Influenza virus infection prevention preparation.   The influenza virus infection prevention preparation according to claim 1 or 2, wherein the carrier contains a water-soluble polymer having a thickening action.   The water-soluble polymer is a natural polymer such as gelatin, casein, hyaluronic acid, tragacanth gum, xanthan gum, pectin, carrageenan, sodium alginate, glucomannan; water-soluble such as methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carmellose The preparation for preventing influenza virus infection according to claim 3, which is selected from cellulosic polymers; and water-soluble synthetic polymers such as povidone, crospovidone, copolydon, polyvinyl alcohol, and sodium polyacrylate.   The preparation for preventing influenza virus infection according to claim 1 or 2, wherein the carrier is liquid and contains a thickening component.   The influenza virus infection prevention preparation according to claim 5, wherein the thickening component is selected from glycerin, propylene glycol, polyethylene glycol and polyoxyethylene sorbitan.