CN101181253B

CN101181253B - Chloromycetin eyedrops with long shelf-life and preparation method thereof

Info

Publication number: CN101181253B
Application number: CN200710190831XA
Authority: CN
Inventors: 张咏梅
Original assignee: Individual
Current assignee: Individual
Priority date: 2007-11-30
Filing date: 2007-11-30
Publication date: 2010-06-02
Anticipated expiration: 2027-11-30
Also published as: CN101181253A

Abstract

The invention discloses a chloramphenicol eye drop with long validity period, including chloramphenicol and buffer solution, and the eye drop contains the D-Sodium isoascorbiate with the weight concentration of 0.01 to 0.05 percent. The chloramphenicol eye drop of the invention can not only be prepared according to the existing processing technique, but can also be prepared according to the following method: the preparation method of the invention includes preparation process and filling-sealing process. Compared with the prior art, the guarantee period of the invention can achieve more than 2years, which is conducive to the production, sales and usage of the chloramphenicol eye drop, so the invention has great benefits for the creation of a conservation-oriented society.

Description

Chloramphenicol Eye Drop that a kind of effect duration is long and preparation method thereof

Technical field

The invention belongs to Chloramphenicol Eye Drop and preparation method thereof, belong to Chloramphenicol Eye Drop that contains sodium D-isoascorbate and preparation method thereof especially.

Background technology

Chloramphenicol Eye Drop 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 long Chloramphenicol Eye Drop of a kind of effect duration and preparation method thereof.

The technical scheme of technical solution problem of the present invention is: the Chloramphenicol Eye Drop that a kind of effect duration is long comprises that containing weight concentration in chloromycetin, buffer, the eye drop is the 0.01-0.05%D-sodium erythorbate.

Containing weight concentration in the preferred Chloramphenicol Eye Drop is the 0.02-0.05%D-sodium erythorbate.

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 Chloramphenicol Eye Drop, described metal chelating agent is EDTA-2Na, a kind of or several mixture of disodium edetate.

Described 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 Chloramphenicol Eye Drop, described antibacterial is one or more a mixture of methyl hydroxybenzoate, ethyl hydroxybenzoate, propylparaben.

Described antibacterial can also be benzalkonium bromide, thimerosal.

Chloramphenicol Eye Drop can also add hyaluronic acid sodium, glycerol.

Chloramphenicol Eye Drop 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 Chloramphenicol Eye Drop 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 Chloramphenicol Eye Drop decomposes in water is a radical reaction, by in Chloramphenicol Eye Drop, increasing sodium D-isoascorbate, and sodium D-isoascorbate is an antioxidant, effect with free radical in the very strong removing solution, by elimination, reach the effect duration of improving Chloramphenicol Eye Drop, the purpose of shelf-life to free radical in the Chloramphenicol Eye Drop.

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 Chloramphenicol Eye Drop, 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 for " the 778th page method is tested 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 sodium D-isoascorbate is to buy on the market.

Embodiment 1:

Extracting chloromycetin 2.5 grams, boric acid 1.5 grams, Borax 0.5 gram, sodium chloride 6.5 grams, sodium D-isoascorbate 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, sodium D-isoascorbate 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, sodium D-isoascorbate 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
	Quickened 4 months	Quickened 8 months	Quickened 12 months	Chloromycetin drug content (%)	97.8	91.2	80.1
Chloromycetin glycol content (%)	Do not have	7.8	12.6	Chloromycetin drug content (%)	97.8	91.2	80.1
Chloromycetin glycol content (%)	Do not have	7.8	12.6	Paranitrobenzaldehyde content (%)	Do not have	0.4	1.8

Embodiment 2 results are as shown in table 2:

Table 2:

	Quickened 4 months	Quickened 8 months	Quickened 12 months
	Quickened 4 months	Quickened 8 months	Quickened 12 months	Chloromycetin drug content (%)	99.6	92.3	81.5
Chloromycetin glycol content (%)	Do not have	7.5	11.5	Chloromycetin drug content (%)	99.6	92.3	81.5
Chloromycetin glycol content (%)	Do not have	7.5	11.5	Paranitrobenzaldehyde content (%)	Do not have	0.4	1.8

Embodiment 3 results are as shown in table 3:

Table 3:

	Quickened 4 months	Quickened 8 months	Quickened 12 months
	Quickened 4 months	Quickened 8 months	Quickened 12 months	Chloromycetin drug content (%)	98.6	92.4	82.1
Chloromycetin glycol content (%)	Do not have	7.4	10.8	Chloromycetin drug content (%)	98.6	92.4	82.1
Chloromycetin glycol content (%)	Do not have	7.4	10.8	Paranitrobenzaldehyde content (%)	Do not have	0.4	1.6

Embodiment 1-3 shows that sodium D-isoascorbate content all can be realized the present invention when 0.01-0.05%.

Embodiment 4:

Except that adding the EDTA-2Na in Chloramphenicol Eye Drop, all the other are identical with embodiment 2.

Embodiment 4 results are as shown in table 4:

Table 4:

	Quickened 4 months	Quickened 8 months	Quickened 12 months
	Quickened 4 months	Quickened 8 months	Quickened 12 months	Chloromycetin drug content (%)	98.5	92.8	85.1

	Quickened 4 months	Quickened 8 months	Quickened 12 months
	Quickened 4 months	Quickened 8 months	Quickened 12 months	Chloromycetin glycol content (%)	Do not have	7.0	9.6
Paranitrobenzaldehyde content (%)	Do not have	0.3	1.4	Chloromycetin glycol content (%)	Do not have	7.0	9.6

In solution, add the stability that chelating agent can improve Chloramphenicol Eye Drop.

Embodiment 5:

Except that being that all the other are identical with embodiment 4 chloromycetin produced of fermentation technology at the used principal agent chloromycetin of Chloramphenicol Eye Drop.

Embodiment 5 results are as shown in table 5:

Table 5:

	Quickened 4 months	Quickened 8 months	Quickened 12 months
	Quickened 4 months	Quickened 8 months	Quickened 12 months	Chloromycetin drug content (%)	101.2	95.6	88.6
Chloromycetin glycol content (%)	Do not have	4.3	7.5	Chloromycetin drug content (%)	101.2	95.6	88.6
Chloromycetin glycol content (%)	Do not have	4.3	7.5	Paranitrobenzaldehyde content (%)	Do not have	0.2	1.2

Embodiment 6:

Except that principal agent being made the granule that contains chloromycetin 0.25 gram, all the other are identical with embodiment 5.

Embodiment 7:

Except that principal agent being made the tablet that contains chloromycetin 0.25 gram, all the other are identical with embodiment 5.

Embodiment 8:

Except that principal agent being made the drop pill that contains chloromycetin 0.25 gram, all the other are identical with embodiment 5.

Embodiment 6-8 is difficult for oxidized decomposition, so its shelf-life can also prolong because principal agent chloromycetin wraps in solid or the semisolid.

Embodiment 9:

Removing production process is:

Earlier adjuvant except that chloromycetin is dropped in the reactor, treat various adjuvants dissolvings after, be under 50,000 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 45 ℃ 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 5.

Embodiment 9 results are as shown in table 6:

Table 6:

	Quickened 4 months	Quickened 8 months	Quickened 12 months
	Quickened 4 months	Quickened 8 months	Quickened 12 months	Chloromycetin drug content (%)	101.5	96.5	89.2
Chloromycetin glycol content (%)	Do not have	3.2	7.1	Chloromycetin drug content (%)	101.5	96.5	89.2
Chloromycetin glycol content (%)	Do not have	3.2	7.1	Paranitrobenzaldehyde content (%)	Do not have	0.1	0.5

Embodiment 10 explanation, the described production technology of the application of the invention can improve the stability of Chloramphenicol Eye Drop.

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

Effect duration long Chloramphenicol Eye Drop, comprise chloromycetin, buffer, it is characterized in that: containing weight concentration in the eye drop is the 0.01-0.05%D-sodium erythorbate.
2. the Chloramphenicol Eye Drop that a kind of effect duration according to claim 1 is grown, it is characterized in that: containing weight concentration in the Chloramphenicol Eye Drop is the 0.02-0.05%D-sodium erythorbate.
3. the Chloramphenicol Eye Drop that a kind of effect duration according to claim 1 is grown, it is characterized in that: add metal chelating agent in Chloramphenicol Eye Drop, described metal chelating agent is a disodium edetate.
4. the Chloramphenicol Eye Drop that a kind of effect duration according to claim 1 is long is characterized in that: described chloromycetin is the chloromycetin of explained hereafter by fermentation.
5. the Chloramphenicol Eye Drop that a kind of effect duration according to claim 1 is grown, it is characterized in that: the pH value of described buffer is 6-6.5.
6. the Chloramphenicol Eye Drop that a kind of effect duration according to claim 1 is long is characterized in that: add antibacterial in Chloramphenicol Eye Drop, described antibacterial is one or more a mixture of methyl hydroxybenzoate, ethyl hydroxybenzoate, propylparaben.
7. the Chloramphenicol Eye Drop that a kind of effect duration according to claim 1 is grown, it is characterized in that: add antibacterial in Chloramphenicol Eye Drop, described antibacterial is a benzalkonium bromide, thimerosal.
8. the preparation method of the Chloramphenicol Eye Drop that a kind of effect duration according to claim 1 is long 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.