KR20200084203A - A drug storage package for storing antiviral and antimicrobial compositions - Google Patents

Abstract

The present invention relates to a drug storage package for storing an antiviral and antimicrobial composition. The drug storage package maintains the pharmacological activity of povidone iodine for a long period of time by storing povidone iodine powder separately from a mixed aqueous solution of water, sodium chloride, and fragrance. By mixing sodium chloride and fragrance, the effect of improving the water solubility of povidone-iodine is excellent, and the effect of shielding the unpleasant odor and taste of povidone-iodine is excellent, making antiviral and antibacterial compositions that can disinfect all tissues of the respiratory system inconveniently used.

Description

A drug storage package for storing antiviral and antimicrobial compositions

The present invention relates to a drug storage package for storing antiviral and antimicrobial compositions with improved storage properties.

Disinfectants are drugs that have a broad spectrum of activity against a number of pathogens that cause infection, and do not develop resistance while destroying bacteria, viruses, and many other microorganisms. In particular, among disinfectants, it is known that iodine disinfectants exhibit a wide range of activities in a short time against various viruses and bacteria.

Povidone Iodine is a chemical combination of polyvinylpyrrolidone (Povidone, PVP) and iodine and usually contains 9 to 12% iodine. It has been widely used as a disinfecting disinfectant for the prevention and treatment of infections in wounded areas, and is known to be effective against yeast, fungi, fungi, viruses, and protozoa. However, despite good activity and wide application, povidone iodine has been prepared and marketed in solution.

10% high concentration povidone iodine solution is relatively stable, but if you want to disinfect your eyes, nasal cavity, oral cavity, or lower respiratory tract, high concentration povidone iodine can damage the cilia, so it cannot be used for mucosal or epithelial layer with cilia, and low concentration of 0.3% or less Only povidone iodine solution can be used. However, in order to provide convenience in use, when the povidone iodine solution is distributed as a dilution solution of a low concentration, the activity of the iodine agent is sharply reduced, thereby shortening the life of the product. In previous papers [Obi C. et al., Annals of Biological Sciences, 3(1), 30-35, 2015], the povidone iodine disinfectant must be re-evaluated and used every month because the disinfecting efficacy rapidly decreases. Reported. Therefore, low concentrations of povidone iodine solution are difficult to circulate or store for a long time, and so far, there have been no commercially available disinfectants containing povidone iodine solution of 0.3% or less.

When a low concentration of povidone iodine solution is to be used, it is required to dilute the high concentration solution immediately before use, but it is inconvenient to dilute and use the high concentration solution, and the commercially available high concentration povidone iodine solution does not have a constant concentration. There is a problem that the general public or the patient cannot make a solution of the correct concentration for the purpose immediately before use.

While the povidone iodine in solution is unstable, the povidone iodine in solid state has very stable characteristics. Solid povidone iodine is stable at a temperature of 65°C as well as room temperature when stored in a sealed state, and the loss of iodine effective for 3 years is about 0.5%. Therefore, the solid state povidone iodine is a very stable material that does not lose activity, and can be a good solution to the storage stability problem because it can be stored for a long time.

However, when using solid povidone iodine in a home or hospital, there is a problem that it takes a long time to dissolve in water. Povidone iodine is water-soluble, but when dissolved in water, it takes a long time to completely dissolve due to problems such as clumping from the surface of the water and sticking to the surface of the container, so that it does not come off easily.

U.S. Patent No. 04950653 discloses that it takes 45 minutes to dissolve povidone iodine in water. In addition, when urea and sugar alcohol are mixed with povidone iodine, it takes more than 2 minutes to dissolve in water, but restrictions apply when applying due to problems such as stability and safety, including urea.

Therefore, there have been no previous reports that mention a drug storage package that stores antiviral and antimicrobial compositions that use solid povidone iodine for storage but improves solubility and provides convenience in use.

U.S. Patent No. 04950653 (Solid iodophor composition, registered on August 21, 1990) U.S. Patent No. 05126127 (Stabilized PVP-I solutions, registered on June 30, 1992)

Obi C. et al., Effectiveness of Povidone iodine solution as a preoperative scrubbing agent in operating theater, Annals of Biological Sciences, 3(1), 30-35, 2015.

The present invention is to provide a drug storage package for storing antiviral and antibacterial compositions with improved storage properties.

The present invention in a drug storage package for storing antiviral and antibacterial compositions,

A body having an accommodation space formed therein;

A partition wall dividing the accommodation space of the body into a first accommodation space and a second accommodation space; And

A cover covering the upper portion of the body to seal the interior; It consists of,

The first accommodating space is filled with povidone iodine powder, and the second accommodating space is filled with a mixed aqueous solution containing water, sodium chloride and fragrance, and when used, the material of the first accommodating space and the second accommodating space is mixed It relates to a drug storage package, characterized in that configured as possible.

The drug storage package according to the present invention, as shown in Figures 1 and 2, the body 20 is formed with a receiving space 30 for storing the drug, the partition wall 40 for partitioning the receiving space of the body and the upper body It includes a cover 50 for covering. The partition wall 40 separates or seals the inner receiving space 30 even when the cover 50 is coupled to the body 20, and separates or seals each, and the first receiving space 31 and the first receiving space 31 are formed by the partition wall 40. It is divided into two accommodation spaces (32). In addition, the partition wall 40 forms a guide portion on the body to be vertically pushed into the guide portion to be inserted or removed, and the guide portion is formed of a water-tight material such as rubber or silicone to tightly separate the divided two receiving spaces. Can be configured.

The povidone iodine powder filled in the first accommodating space contains 0.01 to 0.5w/v% based on the total weight of the water filled in the second accommodating space, and the sodium chloride and fragrance charged in the second accommodating space are second It contains 1 to 5 w/v% sodium chloride and 0.0001 to 0.1 w/v% fragrance based on the total weight of water filled in the receiving space. Particularly, in the case of povidone iodine, the lowest concentration capable of exerting a pharmacological effect is 0.01w/v%, and if the final concentration of povidone iodine contained in the drug storage package is less than 0.01w/v%, antiviral and antibacterial effects are low and thus Unfavorable, if the final concentration of povidone iodine exceeds 0.5w/v%, the irritation is too severe when applied to the respiratory tract, making it unsuitable for use.

The povidone iodine filled in the first accommodation space is used in powder form to improve storage, and the povidone iodine powder preferably has a particle size of 600 µm or less, more preferably 250 µm or less. .

The fragrance filled in the second accommodation space is used to mask the unpleasant or unpleasant odor and taste of povidone iodine, and substances selected from fragrances listed in the International Fragrance Association (IFRA) can be used. It is preferable to use a substance that can be used simultaneously with zero, and it is preferable to use a stable substance that does not react with iodine, and compounds having functional groups such as saturated alkyl, acid, alcohol, ester, ether, lactone, ketone or aromatic are used. It is preferred to use.

More specifically, the fragrance is butyl acetate (butyl acetate), amyl acetate (amyl acetate), isoamyl acetate (isoamyl acetate), hexyl acetate (hexyl acetate), 2-hexyl acetate (2-hexyl acetate), ethyl propionate (ethyl propionate), butyl propionate, isobutyl propionate, isoamyl propionate, ethyl butyrate, ethyl 2-methylbutyrate (ethyl 2- methylbutyrate, butyl isobutyrate, ethyl hexanoate, ethyl pivalate, methyl 4-methylvalerate, ethyl valerate, ethyl Isovalerate, isopropyl isovalerate, ethyl lactate, 2-pentanone, heptanoic acid, 3-heptanone (3- heptanone, 2,3-hexanedione, d-camphor, p-methyl anisole, 2-methoxy-6-methylpyrazine (2- methoxy-6-methyl pyrazine), 1,8-cineole, 1,4-cineole, benzyl methyl ether, 3-heptanol ( 3-heptanol), isoamyl isovalerate, butyl valerate, butyl lactate, methyl benzoate, ethyl benzoate, propyl benzoate (propyl benzoate), butyl benzo Ethyl (butyl benzoate), isobutyl benzoate, amyl benzoate, isoamyl benzoate, methyl phenylacetate, ethyl phenylacetate, benzyl acetate ( benzyl acetate), sassafras acetate, isobornyl acetate, ethyl 3-phenylpropionate, 2-methyl-5-ethoxypyrazine (2-methyl-5 -ethoxypyrazine), 2-methyl-6-ethoxypyrazine, 2,3-diethyl-5-methylpyrazine, 2-methyl- 6,7-dihydro-5H-cyclopentapyrazine, 2-acetyl pyrazine, acetyl pyridine, 2-acetylpyridine (2-acetyl pyridine), 3-acetyl pyridine, 2-t-butyl cyclohexanone, p-dimethyl-hydroquinone, isoquinoline (isoquinoline), 2,3-dimethyl-benzofuran, 3,6-dimethyl benzofuranone, ambernaphthofuran, pt-butyl -Cyclohexanone (pt-butyl-cyclohexanone), thymol methyl ether, 3-phenylpropyl alcohol, 2,6-dimethoxyphenol, 2- t-butyl-6-methyl-phenol (2-t-butyl-6-methyl-phenol), l-menthol, dl-menthol, d-neomenthol, menthone lactone, p-ethyl acetophenone, scatol ( skatole, diphenyl ether, β-naphthyl methyl ether, β-naphthyl ethyl ether, saffron indenone, ambroside ( ambroxide, (-)-ambroxide ((-)-ambroxide), phenylacetic acid, watermelon ketone, dihydroactinidiolide, 3-butylphthalide (3- butyl-phthalide, borneol, dl-isoborneol, thymol, exaltolide, exaltone, menthyl lactate, methyldi Methyl dihydrojasmonate, ethylene brassylate, t-hydrofurfuryl phenylacetate, 2-(3-phenylpropyl)pyridine ), (±)-muscone ((±)-muscone), (-)-muscone ((-)-muscone), isomuscone, normuscone, cyclohexadecanone ), cerestolide, sandal cyclopropane, aniseed oil, eucalyptus oil, and peppermint oil.

The drug storage package of the present invention is preferably used after separating the partition wall partitioning the first receiving space and the second receiving space immediately before use, and then mixing and using all organs of the respiratory system, that is, the eye, nasal cavity, oral cavity, pharynx, and larynx. Since it can disinfect all tissues of the respiratory system, such as the bronchus and lungs, it can be used as an antiviral and antibacterial composition.

The present invention relates to a drug storage package that stores antiviral and antibacterial compositions. The drug storage package maintains the pharmacological activity of povidone iodine for a long time by separately storing the povidone iodine powder with a mixed aqueous solution of water, sodium chloride, and fragrance, and has an excellent effect of improving the water solubility of povidone iodine by mixing sodium chloride and a fragrance. In addition, since the unpleasant smell and taste of povidone iodine are excellent in masking effect, antiviral and antibacterial compositions that can disinfect all tissues of the respiratory system can be used without discomfort.

1 and 2 is a cross-sectional view and a cross-sectional view of the partition wall of the drug storage package.

Hereinafter, a preferred embodiment of the present invention will be described in detail. However, the present invention is not limited to the embodiments described herein and may be embodied in other forms. Rather, the contents introduced herein are thorough and complete, and are provided to sufficiently convey the spirit of the present invention to those skilled in the art.

< Example One. Povidone Preparation of solid composition mixed with iodine, sodium chloride and fragrance>

With reference to Table 1 below, povidone iodine (poly(vinylpyrrolidone)-Iodine complex, 10:1, Sigma-Aldrich, crushed to 600 µm or less), sodium chloride and spices were placed in a mortar and uniformly ground for 5 minutes to form a powder. A solid composition was prepared.

Condition Povidone Iodine (g) Chloride
Sodium (g) Flavoring (g) Used spices (g) Total use
Flavoring amount (g) Example 1 0.2 1.5 Isoamyl Acetate 0.001,
l-menthol 0.002,
(-)-Ambrose seed 0.0006,
Exaltolide 0.0003 0.0039 Example 2 0.2 2.5 Isoamyl Acetate 0.001,
l-menthol 0.002,
(-)-Ambrose seed 0.0006,
Exaltolide 0.0003 0.0039 Example 3 0.2 3.5 Isoamyl Acetate 0.001,
l-menthol 0.002,
(-)-Ambrose seed 0.0006,
Exaltolide 0.0003 0.0039 Example 4 0.1 1.5 Isoamyl Acetate 0.001,
l-menthol 0.002,
(-)-Ambrose seed 0.0006,
Exaltolide 0.0003 0.0039 Example 5 0.1 3.5 Isoamyl Acetate 0.001,
l-menthol 0.002,
(-)-Ambrose seed 0.0006,
Exaltolide 0.0003 0.0039 Example 6 0.3 1.5 Isoamyl Acetate 0.001,
l-menthol 0.002,
(-)-Ambrose seed 0.0006,
Exaltolide 0.0003 0.0039 Example 7 0.3 3.5 Isoamyl Acetate 0.001,
l-menthol 0.002,
(-)-Ambrose seed 0.0006,
Exaltolide 0.0003 0.0039 Example 8 0.01 2.5 Isoamyl Acetate 0.001,
l-menthol 0.002,
(-)-Ambrose seed 0.0006,
Exaltolide 0.0003 0.0039 Example 9 0.5 2.0 Isoamyl Acetate 0.001,
l-menthol 0.002,
(-)-Ambrose seed 0.0006,
Exaltolide 0.0003 0.0039 Example 10 0.5 1.5 Isoamyl Acetate 0.001,
l-menthol 0.002,
(-)-Ambrose seed 0.0006,
Exaltolide 0.0003 0.0039 Example 11 0.1 2.5 d-camper 0.001,
1,8-cineole 0.005,
l-menthol 0.002,
(-)-Ambroside 0.0004,
Exaltolide 0.0002 0.0086 Example 12 0.2 2.5 d-camper 0.001,
1,8-cineole 0.005,
l-menthol 0.002,
(-)-Ambrose seed 0.0006,
Exaltolide 0.0003 0.0089 Example 13 0.2 2.5 2-hexyl acetate 0.0005,
Butylpropionate 0.0005,
Butyl isobutyrate 0.0005,
Ethyl valerate 0.0005,
2-pentanone 0.0005,
l-menthol 0.001,
(-)-Ambroside 0.0004,
Exaltolide 0.0002 0.0041 Example 14 0.2 2.5 Isoamyl Acetate 0.001,
Butyl Valerate 0.0005,
Isobornyl acetate 0.0005,
Isoquinoline 0.0003,
Amber naphthofuran 0.0003,
Exaltolide 0.0002 0.0028 Example 15 0.3 2.5 Isoamyl Acetate 0.001,
l-menthol 0.002,
(-)-Ambrose seed 0.0006,
Exaltolide 0.0003 0.0039

< Comparative example 1. Preparation of Comparative Solid Composition>

Prepared in the same manner as in Example 1, a solid composition of a comparative example was prepared with reference to Table 2 below.

Condition Povidone Iodine (g) Chloride
Sodium (g) Spices Used spices (g) Total use
Flavoring amount (g) Comparative Example 1 0.2 - - - Comparative Example 2 2.5 2.5 - - Comparative Example 3 5 2.5 - - Comparative Example 4 0.2 0.2 - - Comparative Example 5 0.2 0.1 - - Comparative Example 6 0.2 - Isoamyl Acetate 0.001,
l-menthol 0.002,
(-)-Ambrose seed 0.0006,
Exaltolide 0.0003 0.0039 Comparative Example 7 0.2 Sodium sulfate
Anhydride 2.5 - - Comparative Example 8 0.2 Ammonium chloride
2.5 - - Comparative Example 9 0.2 Potassium chloride
2.5 - - Comparative Example 10 0.2 Potassium bromide
2.5 - - Comparative Example 11 0.2 D-mannitol
2.5 - -

< Experimental Example 1. Check storage stability>

To confirm storage stability for the solid composition of the present invention, the solid composition of Examples or Comparative Examples was placed in a 5 ml brown glass vial and the lid was closed. It was stored in a 60°C incubator for 2 weeks, and iodine loss was measured at intervals of 1 week. Examples and comparative examples were repeated three times, the temperature condition of 60 ℃ is a harsh condition for relative comparison of the stability of the drug.

To measure the amount of iodine lost, each sample was taken out at weekly intervals, the mixture in a 5 ml glass vial was dissolved in 100 ml of distilled water and titrated with a standard solution of 0.01N sodium thiosulfate (Samjeon Pure Chemicals) Was quantified. The amount of iodine lost is calculated as 1.269 mg of iodine per ml of a standard solution of 0.01N sodium thiosulfate, and shown in Table 3.

Condition The amount of povidone iodine lost (%) Early 1 week later after 2 weeks Example 2 0 0.75 1.30 Example 2 to 100 ml of water
Dissolved aqueous solution 0 33.0 65.5 Comparative Example 1 in 100 ml of water
Dissolved aqueous solution 0 32.0 70.0

Referring to Table 3, the solid composition of Example 2 containing povidone iodine in powder form, such as the drug storage package of the present invention, had a very small amount of povidone iodine lost within 1.5% for 2 weeks even at a high temperature of 60°C. However, unlike the drug storage package of the present invention, the aqueous solution in which the solid composition of Example 2 was dissolved in water and the aqueous solution in Comparative Example 1 was dissolved in water, and the final amount of povidone iodine lost was 50 times or more compared to the solid composition. When the concentration of povidone iodine was found to be 0.1% or less, it was found that the povidone iodine in aqueous solution had very low storage.

Thus, it has been found that separating and storing the povidone iodine powder and the mixed aqueous solution of water, sodium chloride and fragrance as in the present invention is a method for maintaining povidone iodine having a pharmacological effect for a long time.

< Experimental Example 2. Dissolution rate in water OK>

The compositions of Examples and Comparative Examples were placed in a 100 ml glass bottle, and 100 ml of distilled water at 25°C (± 0.5°C) was added, followed by stirring at 300 rpm in a magnetic stirrer, repeating Examples and Comparative Examples 3 times The experiment was conducted. For the time it takes for the povidone iodine to completely dissolve in water, the time until the moment when the residual of the povidone iodine disappears completely from the base wall of the container in the solution to which distilled water is added is shown in Table 4 below.

Condition Total dissolution time (sec) Example 1 12 Example 2 10 Example 3 7 Example 4 8 Example 5 ≤5 Example 6 13 Example 7 8 Example 8 ≤5 Example 9 15 Example 10 23 Example 11 ≤5 Example 12 10 Example 13 10 Example 14 10 Example 15 12 Comparative Example 1 900 Comparative Example 2 640 Comparative Example 3 650 Comparative Example 4 600 Comparative Example 5 630 Comparative Example 6 930 Comparative Example 7 1044 Comparative Example 8 60 Comparative Example 9 60 Comparative Example 10 120 Comparative Example 11 80

Looking at Table 4, it was confirmed that the solid composition of the embodiment of the present invention has a dissolution rate in water of 30 seconds or less, and is a composition that dissolves in water very quickly.

However, as in Comparative Example 1 and Comparative Example 6, it was found that in the absence of sodium chloride, the dissolution rate in water was 900 seconds or more, that is, 15 minutes or more. In addition, in the case of Comparative Example 7 using sodium sulfate instead of sodium chloride, the dissolution rate in water was very slow, so it took more than 1044 seconds (about 17 minutes), Comparative Example 8 using ammonium chloride, Comparative Example 9 using potassium chloride, and potassium bromide In Comparative Example 10 using D and Comparative Example 11 using D-mannitol, it took 60 to 120 seconds, and the dissolution rate in water was remarkably lower than in Examples of the present invention.

Therefore, in the drug storage package for storing the antiviral and antimicrobial compositions, the amount of loss of the povidone iodine powder, even if it contains povidone iodine at a low concentration, is separated from the mixed aqueous solution of water, sodium chloride, and fragrance as in the present invention. It is maintained for a long time with little or no anti-viral and antibacterial composition that has excellent dissolution rate in water and removes unpleasant odor and taste of povidone iodine by removing only the partition walls without being affected by places such as home or hospital immediately before use. Therefore, it was found that the antiviral and antimicrobial compositions that can disinfect all respiratory system tissues, such as the eyes, nasal cavity, oral cavity, pharynx, larynx, bronchus, and lungs, can be used without discomfort.

10: drug storage package
20: body
30: accommodation space
31: first accommodation space
32: second accommodation space
40: bulkhead
50: cover

Claims (5)

In the drug storage package for storing the antiviral and antibacterial composition,
A body having an accommodation space formed therein;
A partition wall dividing the accommodation space of the body into a first accommodation space and a second accommodation space; And
A cover covering the upper portion of the body to seal the interior; It consists of,
The first accommodating space is filled with povidone iodine powder, and the second accommodating space is filled with a mixed aqueous solution containing water, sodium chloride and fragrance, and when used, the material of the first accommodating space and the second accommodating space is mixed Drug storage package, characterized in that configured as possible. According to claim 1,
The povidone iodine powder filled in the first accommodation space comprises a drug storage package comprising 0.01 to 0.5w/v% based on the total weight of the water filled in the second accommodation space. According to claim 1,
Povidone iodine powder filled in the first accommodation space is a drug storage package, characterized in that less than 600㎛. According to claim 1,
The sodium chloride and the perfume filled in the second receiving space contain the drug storage, characterized in that it contains 1 to 5w/v% sodium chloride and 0.0001 to 0.1w/v% of sodium based on the total weight of the water filled in the second receiving space. package. According to claim 1,
The fragrance is butyl acetate, butyl acetate, amyl acetate, isoamyl acetate, hexyl acetate, 2-hexyl acetate, ethyl propionate ), butyl propionate, isobutyl propionate, isoamyl propionate, ethyl butyrate, ethyl 2-methylbutyrate, Butyl isobutyrate, ethyl hexanoate, ethyl pivalate, methyl 4-methylvalerate, ethyl valerate, ethyl isovalerate (ethyl isovalerate), isopropyl isovalerate, ethyl lactate, 2-pentanone, heptanoic acid, 3-heptanone, 2,3-hexanedione, d-camphor, p-methyl anisole, 2-methoxy-6 -methyl pyrazine), 1,8-cineole, 1,4-cineole, benzyl methyl ether, 3-heptanol ), isoamyl isovalerate, butyl valerate, butyl lactate, methyl benzoate, ethyl benzoate, propyl benzoate ), butyl benzoate (butyl benzoate, isobutyl benzoate, amyl benzoate, isoamyl benzoate, methyl phenylacetate, ethyl phenylacetate, benzyl acetate , Sassafras acetate, isobornyl acetate, ethyl 3-phenylpropionate, 2-methyl-5-ethoxypyrazine , 2-methyl-6-ethoxypyrazine, 2,3-diethyl-5-methylpyrazine, 5-methyl-6,7 -Dihydro-5H-cyclopentapyrazine (5-methyl-6,7-dihydro-5H-cyclopentapyrazine), 2-acetyl pyrazine, acetyl pyridine, 2-acetylpyridine (2- acetyl pyridine, 3-acetyl pyridine, 2-t-butyl cyclohexanone, p-dimethyl-hydroquinone, isoquinoline , 2,3-dimethyl-benzofuran, 3,6-dimethyl benzofuranone, ambernaphthofuran, pt-butyl-cyclohexane On (pt-butyl-cyclohexanone), thymol methyl ether, 3-phenylpropyl alcohol, 2,6-dimethoxyphenol, 2-t-butyl -6-methyl-phenol (2-t-butyl-6-methyl-phenol), l-menthol (l-men thol), dl-menthol, d-neomenthol, menthone lactone, p-ethyl acetophenone, skatole, diphenyl ether (diphenyl ether), β-naphthyl methyl ether, β-naphthyl ethyl ether, saffron indenone, ambrooxide, (-) -Ambroside ((-)-ambroxide), phenylacetic acid, watermelon ketone, dihydroactinidiolide, 3-butyl-phthalide, bor Borneol, dl-isoborneol, thymol, exaltolide, exaltone, menthyl lactate, methyldihydrozasmonate (methyl dihydrojasmonate, ethylene brassylate, t-hydrofurfuryl phenylacetate, 2-(3-phenylpropyl)pyridine, (±)- Muscon ((±)-muscone), (-)-muscone ((-)-muscone), isomuscone, normuscone, cyclohexadecanone, and cyclosdelide ( A drug storage package comprising at least one selected from celestolide, sandal cyclopropane, aniseed oil, eucalyptus oil and peppermint oil.

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