CN1203864C - Spray formulation of providone iodine - Google Patents

Abstract

The invention discloses a povidone-iodine spray, which is characterized in that it contains active agents povidone-iodine, potassium iodate and/or potassium iodide, glycerin and/or propylene glycol, flavoring agents and water. It not only has stable quality, Moreover, it is non-irritating to the skin and sticky touch, and is suitable for oral use to prevent and treat bacterial, fungal and viral infections.

Description

povidone iodine spray

1. Technical field

The invention relates to the field of pharmaceutical preparations, in particular to a spray containing povidone-iodine.

2. Technical background

At present, the medication status of oral diseases and pharyngitis in our country is roughly as follows: oral surgery (such as tooth extraction, tooth correction, etc.) generally uses antibiotics to prevent wound infection, and the effect is good, but it is a systemic medication, which is not the most reasonable medication. Oral medicine, such as the treatment of inflammation such as oral ulcers, is mainly based on topical anti-inflammatory drugs, but there is a lack of topical drugs with ideal curative effect. Oral anti-inflammatory and antibacterial drugs are also used as the main treatment method for various infections of the throat position.

Povidone iodine is a soluble complex formed by iodine and polyvinylpyrrolidone (PVP). Compared with iodine, it has the advantages of good water solubility and low volatility. It is a broad-spectrum, high-efficiency, low-toxicity and safe disinfectant. The 2000 edition of "Chinese Pharmacopoeia" has included povidone-iodine solution, ointment, suppository, gel and other dosage forms, so that povidone-iodine can be widely used clinically. However, there is still a lack of dosage forms suitable for oral use.

3. Contents of the invention

The object of the present invention is to provide a povidone-iodine spray, which not only has little irritation, good safety, is suitable for the skin, especially for oral cavity and throat, and has stable quality and can be produced and used as medicine.

Below is the detailed content of the present invention:

Povidone-iodine spray of the present invention contains the following components by weight percentage:

Povidone-iodine 2-10%

Potassium iodate and/or potassium iodide 0.05-2.5%

Glycerin and/or Propylene Glycol 5-60%

Flavoring agent 0.1-3%

The balance is water

It can further contain 0.1-2% Tween-80.

The flavoring agent is preferably menthol and/or chocolate essence.

Spray of the present invention, preferred formula is as follows:

Povidone-iodine 50g

Potassium iodate 1g

Potassium iodide 1.5g

Glycerin 200ml

Propylene Glycol 100ml

Tween-80 1g

Menthol 2g

Add water to 1000ml

Povidone-iodine is a soluble complex of iodine and polyvinylpyrrolidone. Compared with iodine, it has the advantages of good water solubility and low volatility. However, the available iodine of povidone-iodine will gradually decompose during storage, and certain stabilizers need to be added in the preparation to make the quality of the preparation stable, and the prepared preparation must be non-irritating or extremely small.

Potassium iodate can be used as a stabilizer in the present invention, and it is a kind of strong oxidizing agent, makes the reduction product iodine negative ion of free iodine be oxidized into iodine, and keeps bactericidal activity.

Potassium iodide can form a soluble complex with iodine to help dissolve and stabilize iodine from volatilization. And the complexation reaction is reversible, so the bactericidal power of iodine can still be maintained.

Glycerin: As a sweetener; it can also be used as a solvent for iodine, which can alleviate the irritation of iodine; and it is easy to adhere to the skin or mucous membrane, so that the drug stays in the affected area and plays a prolonging effect.

Propylene Glycol: It is a good dispersant and has a suitable viscosity.

Chocolate essence: can mask the peculiar smell of iodine.

Menthol: In addition to the peculiar smell of iodine, povidone-iodine solution also has a bitter taste. The local anesthetic effect of menthol is also effective in masking the bitter taste, so menthol can also be used for flavoring.

Tween-80: Increases dispersion.

In this formula, potassium iodate and potassium iodide are added to stabilize the active ingredient povidone iodine, and glycerin, propylene glycol, and Tween-80 are added as dispersants and cosolvents, which can improve the absorption rate and absorption amount of the administration site. Agents can mask odors, making them more acceptable to patients and increasing medication compliance.

The preparation method of spray of the present invention is as follows:

Stir and dissolve povidone-iodine with 1/3 of water to obtain solution I. Mix and stir glycerin and/or propylene glycol and 1/3 water to obtain solution II. Combine solution I and solution II and stir to obtain solution III. Separately dissolve potassium iodide and potassium iodate with a small amount of water and add, stir until uniform, add Tween-80, flavoring agent, add water to the total amount, and stir well. Serve in a container with a spout. When using it, just spray it lightly, and the liquid medicine will be evenly distributed on the surface of the skin or mucous membrane, and absorbed quickly to achieve the therapeutic effect.

Utilize the formulation of the present invention and the spray preparation of preparation method to be stable in storage, following are some stability test results:

(1), test basis: Chinese Pharmacopoeia 2000 edition two

(2), sample and batch number: povidone iodine spray, content 10%, batch number: 000918, 000920, 000925.

(3), testing items and testing methods:

Properties: visual inspection.

pH value: Measured according to the provisions of the Chinese Pharmacopoeia 2000 edition two appendix VIH pH determination method.

Content: determined according to the Chinese Pharmacopoeia 2000 edition povidone-iodine solution content determination method.

(4) Test results:

1. The accelerated test results are shown in Table 1.

2. See Table 2 for the long-term test results.

(5), conclusion: carry out stability test and content determination according to Chinese Pharmacopoeia 2000 edition two twos, quality accords with the regulation.

Table 1 Results of accelerated stability test (30°C) of povidone-iodine spray batch number time (months) character pH value Content (marked amount %) 000918 0 reddish brown liquid 5.33 11.09 1 reddish brown liquid 5.38 10.90 2 reddish brown liquid 5.32 10.81 3 reddish brown liquid 5.27 10.63 6 reddish brown liquid 5.29 10.31 000920 0 reddish brown liquid 5.46 11.02 1 reddish brown liquid 5.31 10.91 2 reddish brown liquid 5.33 10.88 3 reddish brown liquid 5.30 10.49 6 reddish brown liquid 5.22 10.17 000925 0 reddish brown liquid 5.35 11.50 1 reddish brown liquid 5.34 11.43 2 reddish brown liquid 5.41 11.17 3 reddish brown liquid 5.22 10.88 6 reddish brown liquid 5.21 10.59

Table 2 Observation test results of povidone-iodine spray at room temperature batch number time (months) character pH value Content (marked amount %) 000918 0 reddish brown liquid 5.23 11.27 1 reddish brown liquid 5.25 11.25 2 reddish brown liquid 5.04 11.10 3 reddish brown liquid 5.08 11.19 6 reddish brown liquid 5.28 11.01 9 reddish brown liquid 5.24 10.90 12 reddish brown liquid 5.33 11.09 18 reddish brown liquid 5.58 11.38 twenty four reddish brown liquid 5.02 11.31 31 reddish brown liquid 5.04 10.54 000920 0 reddish brown liquid 5.46 11.01 1 reddish brown liquid 5.52 10.90 2 reddish brown liquid 5.45 10.98 3 reddish brown liquid 5.50 10.83 6 reddish brown liquid 5.45 10.92 9 reddish brown liquid 5.44 10.90 12 reddish brown liquid 5.48 11.02 18 reddish brown liquid 5.53 11.35 twenty four reddish brown liquid 4.87 10.68 31 reddish brown liquid 4.89 9.79 000925 0 reddish brown liquid 5.35 11.77 1 reddish brown liquid 5.49 11.61 2 reddish brown liquid 5.36 11.65 3 reddish brown liquid 5.38 11.65 6 reddish brown liquid 5.36 11.56 9 reddish brown liquid 5.35 11.53 12 reddish brown liquid 5.39 11.50 18 reddish brown liquid 5.53 11.78 twenty four reddish brown liquid 4.97 11.31 31 reddish brown liquid 4.98 10.46

Another advantage of the invention is that the prepared spray is safe, less irritating, suitable for use on skin, especially for mucous membrane and throat, and has no toxic and side effects.

Below is the part pharmacology research data of spray of the present invention:

1. Acute toxicity test of povidone-iodine spray oral administration

Summary

Povidone-iodine spray was administered orally to rabbits for 4 hours, and the dose was calculated on the basis of body surface area, which was about 51.1 times that of human clinical use. It did not produce obvious toxic effects on rabbits, and none of the rabbits died after 7 days. LD50 is greater than 3.8ml/kg.

(1). Purpose of the test:

To observe the toxic reaction and death after the test substance was administered to rabbits.

(2). Test materials:

1. Test substance:

Povidone-iodine spray of the present invention;

Povidone-iodine spray excipient.

3. Test animals:

New Zealand white rabbits weigh about 2.5kg, half male and half male.

(3). Test method:

1. Selection of dose: choose a dose 50 times greater than the clinical dose, 3.8ml/kg.

2. Test method: Take 12 above-mentioned rabbits and divide them into 3 groups at random, with 4 rabbits in each group, half male and half male. The three groups are povidone-iodine spray dosage group, vehicle group and blank group respectively. control group. When administering the povidone-iodine spray dosage group and the excipient group, open the mouth of the rabbit, aim the spray port at the mouth of the rabbit, and spray the medicine respectively, 3 sprays each time, once every 10 minutes , A total of 24 sprays within 4 hours, that is, the total volume of administration is about 3.80ml/kg. Immediately after administration, observe for 7 consecutive days, record the rabbit's general condition, changes in body weight, respiration, circulation, central nervous system, limb activities, etc. If death occurs, histopathological examination should be done.

(4). Test results:

After administration, the body weight of the rabbits increased, and there was no significant change in breathing, circulation, central nervous system, and limb activities. Seven days later, none of the rabbits in the povidone-iodine spray group, the vehicle group, and the blank control group died.

(5). Test conclusion

Oral administration of povidone-iodine spray to rabbits did not produce obvious toxic effects on rabbits, and the LD50 was greater than 3.80ml/kg.

Attached table: Changes in body weight, respiration, and heartbeat of rabbits after oral administration of povidone-iodine spray in large doses:

group Test time Body weight (kg) (X±SD) Respiration (times) (X±SD) Heartbeat (times) (X±SD) Blank control group Before administration 2.43±0.13 179±20 60.5±10.2 The third day after administration 2.53±0.13 181±12 57.5±10.5 Seventh day after administration 2.70±0.09 174±14 56.5±7.5 Excipient group Before administration 2.50±0.16 189±27 62.0±13.0 The third day after administration 2.60±0.16 188±16 64.0±7.0 Seventh day after administration 2.74±0.22 177±16 60.0±9.1 povidone iodine spray group Before administration 2.58±0.19 176±30 58.5±9.4 The third day after administration 2.69±0.21 170±9 58.5±6.8 Seventh day after administration 2.80±0.20 181±8 61.5±9.7

Note: The changes in body weight, respiration, and heartbeat of the rabbits in this table on the third day and the seventh day after administration were compared with those before administration, and there was no significant difference.

References: Compendium of Guiding Principles for Preclinical Research of New Drugs (Western Medicine) (Pharmacy Pharmacology Toxicology) P219-220

2. Povidone-iodine spray oral administration stimulation test

Summary

Povidone-iodine spray was administered orally to rabbits for 4 hours, and the dose was calculated on the basis of body surface area, which was about 24.77 times that of human clinical use, and did not produce significant stimulation to rabbits.

(1). Purpose of the test:

Observe the stimulation response of the test substance given to rabbits.

(2). Test materials:

1. Test substance: Povidone-iodine spray of the present invention, batch number: 000925.

2. Reference substance: Povidone-iodine spray excipient.

3. Experimental animals: New Zealand white rabbits, weighing about 2.5kg, both male and female.

(3) Test method:

The 9 rabbits mentioned above were randomly divided into 3 groups, 3 rabbits in each group, both male and female, and the 3 groups were divided into povidone-iodine spray dose group, vehicle group and blank control group.

When the povidone-iodine spray dose group and the excipient group were administered, the rabbit's mouth was stretched open, the spray port was aimed at the rabbit's oral cavity, and the medicine was sprayed respectively, 3 sprays each time, and 1 spray every 20 minutes. times, a total of 12 sprays within 4 hours, that is, the total volume of administration is about 1.9ml/kg. The rabbits were executed 24 hours after the administration, and the rabbit's mouth was cut open to observe whether the oral mucosa was congested, red and swollen, etc., and the mucosa in the cheek was taken for tissue section examination.

(4). Test results:

The rabbits were dissected 24 hours after the administration, and the oral mucosa of the rabbits in the povidone-iodine spray group, the vehicle group and the blank control group had no hyperemia, redness and swelling.

(5). Test conclusion

Oral administration of povidone-iodine spray to rabbits did not stimulate the oral mucosa of rabbits. The measurement is converted according to the body surface area, which is about 24.77 times of the human clinical dosage.

References: Compendium of Guiding Principles for Preclinical Research of New Drugs (Western Medicine) (Pharmacy Pharmacology Toxicology) P220

3. Oral administration of povidone-iodine spray to mice for acute toxicity test

Summary

The maximum dose of povidone-iodine spray mice administered once is 40ml/kg.

(1). Purpose of the test:

Observe the toxic reaction and death after the test substance is given to the mice once.

(2). Test materials:

1. Tested substance: Povidone-iodine spray of the present invention, batch number: 000925.

2. Experimental animals: Kunming white mice, weighing about 19g-21g, male and female.

(3). Test method:

Get this product, after the preliminary test, get the above-mentioned 20 mice, half male and half male, and give it to the stomach once by povidone iodine spray stock solution, 0.8ml/20g, that is, the dose is 40ml/kg. Immediately after administration, observe for 7 consecutive days, and record the toxicity and death of the mice. If there is death, an autopsy should be carried out in time. If there are lesions visible to the naked eye, histopathological examination should be done.

(4). Test results:

There was no obvious abnormal reaction in the mice after administration, and none of the mice died seven days later.

(5). Test conclusion

The maximum dose of povidone-iodine spray mice once intragastric administration is 40ml/kg. Converted according to the body surface area, it is about 195.5 times of the human clinical dose.

References: Compendium of Guiding Principles for Preclinical Research of New Drugs (Western Medicine) (Pharmacy Pharmacology Toxicology) P.198-199

Fourth, the specific implementation method:

Example 1

Povidone-iodine 50g

Potassium iodate 1g

Potassium iodide 1.5g

Glycerin 200ml

Propylene Glycol 100ml

Tween-80 1g

Menthol 2g

Add water to 1000ml

Stir and dissolve povidone-iodine with 1/3 of water to obtain solution I. Mix and stir glycerin and/or propylene glycol and 1/3 water to obtain solution II. Combine solution I and solution II and stir to obtain solution III. Separately dissolve potassium iodide and potassium iodate with a small amount of water and add, stir until uniform, add Tween-80, menthol, chocolate essence, add water to the total amount, and stir well. Serve in a container with a spout.

Example 2

Povidone-iodine 50g

Potassium iodate 1g

Glycerin 300ml

Tween-80 1g

Menthol 2g

                                                                                                         ,

Add water to 1000ml

The preparation method is the same as in Example 1.

Claims (4)

1. A spray of povidone-iodine, characterized in that it contains the following components by weight percentage: Povidone-iodine 2-10% Potassium iodate and potassium iodide 0.05-2.5% Glycerin and/or Propylene Glycol 5-60% Flavoring agent 0.1-3% The balance is water. 2. The spray as claimed in claim 1, which further contains 0.1-2% Tween-80 by weight. 3. The spray as claimed in claim 1, wherein the flavoring agent is menthol and/or chocolate essence. 4. The spray according to claim 1, consisting of the following components and weight: Povidone-iodine 50g Potassium iodate 1g Potassium iodide 1.5g Glycerin 200ml Propylene Glycol 100ml TW-80 1g Menthol 2g Add water to 1000ml.