CN100553681C - A kind of Alficetin eye solution and preparation method thereof - Google Patents

Abstract

The invention discloses a kind of Alficetin eye solution, comprise chloromycetin, buffer, containing weight concentration in the solution is the 0.01-0.05% Herba Rosmarini Officinalis extract, Alficetin eye solution of the present invention promptly can be prepared according to existing manufacturing technique, also can be prepared by following method, preparation method of the present invention comprises preparation process, embedding operation, the present invention compared with prior art, shelf-life can reach more than 2 years, help the producing and selling and the use of Alficetin eye solution, the society that creates economizing type is had very big benefit.

Description

A kind of Alficetin eye solution and preparation method thereof

Technical field

The invention belongs to Alficetin eye solution and preparation method thereof, belong to Alficetin eye solution that contains Herba Rosmarini Officinalis extract and preparation method thereof especially.

Background technology

Alficetin eye solution also claims Chloramphenicol Eye Drop, it is a kind of eye medicine commonly used, be " two medicines that recorded of Chinese pharmacopoeia version in 2005, once as the use of on market, circulating of OTC Class A medicine, its Main Ingredients and Appearance is chloromycetin, buffer, antibacterial, water, also have in Chloramphenicol Eye Drop, to add hyaluronic acid sodium, glycerol, improve retention time at eye to strengthen viscosity.The common shelf-life of medicine is 2 years, and the shelf-life of Chloramphenicol Eye Drop can only reach 8-12 month, this is owing to chloromycetin in the Chloramphenicol Eye Drop resolves into the chloromycetin glycol easily, paranitrobenzaldehyde, chloromycetin glycol and paranitrobenzaldehyde have stronger zest to eyes, influence patient's use, therefore " in the Chinese pharmacopoeia version in 2005, content to chloromycetin glycol in the Chloramphenicol Eye Drop and paranitrobenzaldehyde has all been made regulation, be that the content of chloromycetin glycol must not be and is higher than 8% of drug content, the content of paranitrobenzaldehyde must not be higher than 0.5% of drug content.

Chinese patent CN1872038A has introduced drop pill type eye drip fluid of chloramphenicol and preparation method thereof, it isolates chloromycetin and aqueous solution by principal agent chloromycetin being prepared into drop pill, thereby reach the purpose that prolongs expiration date of drug, but because the dissolubility of chloromycetin in water is slightly soluble, above-mentioned medicine in use, must jolting just can make the chloromycetin dissolving for a long time, therefore be unfavorable for patient's use.

Chinese patent CN1163266C discloses a kind of collyrium for the treatment of conjunctivitis and keratitis oculopathy, it steps new protein stabiliser and alpha-interferon by adding in Chloramphenicol Eye Drop, improved it to golden Portugal bacterium, colibacillary sterilizing rate, but the shelf-life of the said goods can only reach 1 year.

Summary of the invention

Technical problem to be solved by this invention provides Alficetin eye solution of a kind of long shelf-life and preparation method thereof.

The technical scheme of technical solution problem of the present invention is: Alficetin eye solution comprises that containing weight concentration in chloromycetin, buffer, the solution is the 0.01-0.05% Herba Rosmarini Officinalis extract.

Containing weight concentration in the preferred Chloramphenicol Eye Drop is the 0.03-0.05% Herba Rosmarini Officinalis extract.

For the ability of the removing free radical that strengthens Herba Rosmarini Officinalis extract, the concentration of can also gaining in weight is vitamin C, the vitamin E of 0.01-0.05%.

Because be subjected to the influence of each metal ion species easily in the process for preparation, so also can add metal chelating agent in Alficetin eye solution, described metal chelating agent is EDTA-2Na, a kind of or several mixture of disodium edetate.

Described principal agent chloromycetin also can be made into drop pill, tablet, granule form.

Described chloromycetin is the chloromycetin of explained hereafter by fermentation.

Described ph value of buffer solution is 6-6.5.

Also can add antibacterial in the Alficetin eye solution, described antibacterial is one or more a mixture of methyl hydroxybenzoate, ethyl hydroxybenzoate, propylparaben.

Described antibacterial can also be benzalkonium bromide, thimerosal.

Alficetin eye solution can also add hyaluronic acid sodium, glycerol.

Alficetin eye solution of the present invention promptly can be prepared according to existing manufacturing technique, also can be prepared by following method, and following method is preferable.

Preparation method of the present invention comprises preparation process, embedding operation:

Described preparation process is:

Earlier the adjuvant except that chloromycetin is dropped in the reactor; after treating various adjuvant dissolvings; be to be not less than 10 minutes with ultrasonic degas under the condition of ten thousand hertz of 2-5 with solution in frequency; after treating the solution degassing fully; add principal agent chloromycetin; under nitrogen protection,, be cooled to room temperature and get final product in 30-50 ℃ of stirring 30-60 minute.

Described embedding operation is: drop into reactor from principal agent chloromycetin and pick up counting, the embedding time must not be above 5 hours.

It has been generally acknowledged that pH value when Alficetin eye solution is 7 when following, main degradation reaction is an amide hydrolysis, generates amino substance and dichloroacetic acid.When adjusting the buffer agent consumption, make pH drop to 5.8 by original 6.4, the stability of Chloramphenicol Eye Drop is improved.

The applicant thinks, the dominant response that the Alficetin eye solution eye drop decomposes in water is a radical reaction, by in Alficetin eye solution, increasing Herba Rosmarini Officinalis extract, and Herba Rosmarini Officinalis extract is an antioxidant, effect with free radical in the very strong removing solution, by elimination to free radical in the Chloramphenicol Eye Drop, reach the stability that improves Alficetin eye solution, prolong its effect duration, shelf-life.

Usage and dosage: external.Eye drip, each 1-2 drips 3-5 time on the one.

The present invention compared with prior art, the shelf-life can reach more than 2 years, helped the producing and selling and the use of Alficetin eye solution, and the society that creates economizing type is had very big benefit.

The specific embodiment:

Below in conjunction with embodiment the present invention is described in detail.

The detection method of content of chloromycetin, chloromycetin glycol, paranitrobenzaldehyde is the " method of inspection of the 778th page of Chloramphenicol Eye Drop in two ones of the Chinese pharmacopoeia versions in 2005 in of the present invention.

Accelerated test of the present invention is: during whole accelerated tests, all that embodiment is made sample is placed in the baking oven of 40 ± 2 ℃ of temperature.1 month of accelerated test is equivalent to 3 months of normal room temperature.

Described Herba Rosmarini Officinalis extract is to buy on the market, and the weight concentration that wherein contains rosmarinic acid is 10% (HPLC).

Embodiment 1:

Extracting chloromycetin 2.5 grams, boric acid 1.5 grams, Borax 0.5 gram, sodium chloride 6.5 grams, Herba Rosmarini Officinalis extract 0.1 gram, water is added to 1000 milliliters and gets final product, and the solution pH value is 6.3.

Embodiment 2:

Extracting chloromycetin 2.5 grams, boric acid 1.5 grams, Borax 0.5 gram, sodium chloride 6.5 grams, Herba Rosmarini Officinalis extract 0.3 gram, water is added to 1000 milliliters and gets final product.

Embodiment 3:

Extracting chloromycetin 2.5 grams, boric acid 1.5 grams, Borax 0.5 gram, sodium chloride 6.5 grams, Herba Rosmarini Officinalis extract 0.5 gram, water is added to 1000 milliliters and gets final product.

Embodiment 1 result is as shown in table 1:

Table 1:

	Quickened 4 months	Quickened 8 months	Quickened 12 months
				Chloromycetin drug content (%)	100.6	91.5	85.2
Chloromycetin glycol content (%)	Do not have	6.9	7.9
				Paranitrobenzaldehyde content (%)	Do not have	0.3	0.6

Embodiment 2 results are as shown in table 2:

Table 2:

	Quickened 4 months	Quickened 8 months	Quickened 12 months
				Chloromycetin drug content (%)	98.4	92.8	87.4
Chloromycetin glycol content (%)	Do not have	6.4	7.5
				Paranitrobenzaldehyde content (%)	Do not have	0.3	0.5

Embodiment 3 results are as shown in table 3:

Table 3:

	Quickened 4 months	Quickened 8 months	Quickened 12 months
				Chloromycetin drug content (%)	99.3	93.2	89.2
Chloromycetin glycol content (%)	Do not have	6.2	7.4

Paranitrobenzaldehyde content (%)

Do not have

0.3

0.5

Embodiment 1-3 shows that Herba Rosmarini Officinalis extract content all can be realized the present invention when 0.01-0.05%.

Embodiment 4:

Except that the concentration of gaining in weight was 0.03% vitamin C, all the other were identical with embodiment 2.

Embodiment 4 results are as shown in table 4:

Table 4:

	Quickened 4 months	Quickened 8 months	Quickened 12 months
				Chloromycetin drug content (%)	99.7	93.5	89.3
Chloromycetin glycol content (%)	Do not have	6.1	7.2
				Paranitrobenzaldehyde content (%)	Do not have	0.2	0.4

Embodiment 4 explanation, weight concentration are the stability that 0.03% vitamin C can improve the Alficetin eye solution that contains Herba Rosmarini Officinalis extract.

Embodiment 5:

Except that adding the EDTA-2Na in Alficetin eye solution, all the other are identical with embodiment 4.

Embodiment 5 results are as shown in table 5:

Table 5:

	Quickened 4 months	Quickened 8 months	Quickened 12 months
				Chloromycetin drug content (%)	97.8	93.8	89.6
Chloromycetin glycol content (%)	Do not have	5.8	7.1
				Paranitrobenzaldehyde content (%)	Do not have	0.2	0.4

In solution, add the stability that chelating agent can improve Alficetin eye solution.

Embodiment 6:

Except that being that all the other are identical with embodiment 5 chloromycetin produced of fermentation technology at the used principal agent chloromycetin of Alficetin eye solution.

Embodiment 6 results are as shown in table 6:

Table 6:

	Quickened 4 months	Quickened 8 months	Quickened 12 months
				Chloromycetin drug content (%)	97.5	94.6	90.1
Chloromycetin glycol content (%)	Do not have	5.4	6.8
				Paranitrobenzaldehyde content (%)	Do not have	0.1	0.4

Embodiment 6 explanations, the chloromycetin of use fermentation technology production can improve the stability of Alficetin eye solution.

Embodiment 7:

Except that principal agent being made the granule that contains chloromycetin 0.25 gram, all the other are identical with embodiment 6.

Embodiment 8:

Except that principal agent being made the tablet that contains chloromycetin 0.25 gram, all the other are identical with embodiment 6.

Embodiment 9:

Except that principal agent being made the drop pill that contains chloromycetin 0.25 gram, all the other are identical with embodiment 6.

Embodiment 7-9 is difficult for oxidized decomposition, so its shelf-life can also prolong because principal agent chloromycetin wraps in solid or the semisolid.

Embodiment 10:

Removing production process is:

Earlier adjuvant except that chloromycetin is dropped in the reactor, treat various adjuvants dissolvings after, be under 40,000 hertz the condition with ultrasonic degas 30 minutes with solution in frequency; after treating the solution degassing fully; add principal agent chloromycetin, under nitrogen protection,, be cooled to room temperature and get final product in 40 ℃ of stirrings 60 minutes.Drop into reactor from principal agent chloromycetin and pick up counting, the embedding time is 3.5 hours, and outer, all the other are identical with embodiment 6.

Embodiment 10 results are as shown in table 7:

Table 7:

	Quickened 4 months	Quickened 8 months	Quickened 12 months
				Chloromycetin drug content (%)	101.3	95.8	91.8

Chloromycetin glycol content (%)	Do not have	5.1	6.3
				Paranitrobenzaldehyde content (%)	Do not have	0.1	0.4

Embodiment 10 explanation, the described production technology of the application of the invention can improve the stability of Alficetin eye solution.

In conjunction with the embodiments the present invention has been carried out exemplary description above; obviously specific implementation of the present invention is not subjected to the restriction of aforesaid way; as long as adopted the improvement of the various unsubstantialities that method of the present invention design and technical scheme carry out; or design of the present invention and technical scheme are directly applied to other occasion without improving, all within protection scope of the present invention.

Claims (9)

1, a kind of Alficetin eye solution comprises chloromycetin, buffer, it is characterized in that: containing weight concentration in the solution is the 0.01-0.05% Herba Rosmarini Officinalis extract.

2, a kind of Alficetin eye solution according to claim 1 is characterized in that: containing weight concentration in the Alficetin eye solution is the 0.03-0.05% Herba Rosmarini Officinalis extract.

3, a kind of Alficetin eye solution according to claim 1 is characterized in that: contain vitamin C, vitamin E that weight concentration is 0.01-0.05% in the Alficetin eye solution.

4, a kind of Alficetin eye solution according to claim 1 is characterized in that: add metal chelating agent in Alficetin eye solution, described metal chelating agent is a disodium edetate.

5, a kind of Alficetin eye solution according to claim 1 is characterized in that: described chloromycetin is the chloromycetin of explained hereafter by fermentation.

6, a kind of Alficetin eye solution according to claim 1 is characterized in that: the pH value of described buffer is 6-6.5.

7, a kind of Alficetin eye solution according to claim 1 is characterized in that: add antibacterial in Alficetin eye solution, described antibacterial is one or more a mixture of methyl hydroxybenzoate, ethyl hydroxybenzoate, propylparaben.

8, a kind of Alficetin eye solution according to claim 1 is characterized in that: add antibacterial in Alficetin eye solution, described antibacterial is a benzalkonium bromide, thimerosal.

9, the preparation method of a kind of Alficetin eye solution according to claim 1 is characterized in that: comprise preparation process, embedding operation:

Described preparation process is:

Earlier the adjuvant except that chloromycetin is dropped in the reactor, after treating various adjuvant dissolvings, be to be not less than 10 minutes with ultrasonic degas under the condition of ten thousand hertz of 2-5 with solution in frequency, after treating the solution degassing fully, add principal agent chloromycetin, under nitrogen protection,, be cooled to room temperature and get final product in 30-50 ℃ of stirring 30-60 minute;

Described embedding operation is: drop into reactor from principal agent chloromycetin and pick up counting, the embedding time must not be above 5 hours.