CN115836681A

CN115836681A - Phthalic dicarboxaldehyde disinfectant and preparation method thereof

Info

Publication number: CN115836681A
Application number: CN202211464576.4A
Authority: CN
Inventors: 张明辉; 张玺; 林文程
Original assignee: Shanghai Likang Disinfection High Tech Co ltd; Likang Pharmaceutical Technology Jiangsu Co ltd
Current assignee: Shanghai Likang Disinfection High Tech Co ltd; Likang Pharmaceutical Technology Jiangsu Co ltd
Priority date: 2022-11-22
Filing date: 2022-11-22
Publication date: 2023-03-24

Abstract

An o-phthalaldehyde disinfectant and a preparation method thereof, the formula of which is as follows: 0.5 to 0.6 percent of o-phthalaldehyde; 0.1% -2% of chelating agent; 1% -10% of hydroxyl ethylidene diphosphonic acid; 1% -5% of a buffering agent; 0.1 to 2.5 percent of dispersant; the balance of pure water; the chelating agent is at least one of ethylenediamine tetraacetic acid, disodium ethylenediamine tetraacetic acid, citrate, pyrophosphate and thiosulfate; the buffer is at least one of ammonium acetate, ammonium chloride, phosphate, carbonate and sodium thiosulfate; the dispersant is at least one of salicylic acid, polyethylene glycol, 1,3-butanediol, etc. The preparation method comprises adding o-phthalaldehyde into a part of pure water, heating, stirring and dissolving to obtain solution A; adding a chelating agent, hydroxyethylidene diphosphonic acid and a dispersing agent into the balance of pure water, and stirring to obtain a solution B; mixing and stirring the solution A and the solution B, reacting, adding a buffering agent, stirring, and adjusting the pH value to 8.5-9.0 to obtain the product.

Description

Phthalic dicarboxaldehyde disinfectant and preparation method thereof

Technical Field

The invention belongs to the field of chemical disinfection product preparations, and particularly relates to an o-phthalaldehyde disinfectant and a preparation method thereof.

Background

Ortho-phthalaldehyde (OPA) is an important pharmaceutical and chemical intermediate before, and after Alaf in 1994 finds that OPA has a good effect on disinfection of medical endoscopes, foreign researches on OPA disinfection functions are active, and the OPA has been developed into a novel high-efficiency disinfectant and is certified by the FDA in the united states. Compared with glutaraldehyde, which is a disinfectant widely adopted in medical institutions at present, o-phthalaldehyde has the advantages of wider sterilization spectrum, lower use concentration, shorter sterilization time, less irritation and weaker corrosivity. It has been used gradually in recent years to replace glutaraldehyde as a new generation of high-efficiency medical disinfectant.

The biological activity of OPA is mainly characterized in that the aldehyde group and amino acid, protein and amino acid groups of other components of microorganisms are subjected to cross-linking reaction rapidly, on one hand, the aldehyde group is used as a sterilization mechanism, and on the other hand, the aldehyde group and the protein react to generate a browning effect. Under acidic or alkaline conditions, the bacillus subtilis can generate black brown, green and black changes on thalli of escherichia coli, pseudomonas aeruginosa and staphylococcus aureus. In the process of cleaning the endoscope by using the o-phthalaldehyde disinfectant in practice, residual protein in the endoscope reacts with aldehyde groups to cause grey staining, and the skin of an operator can quickly change color once touching the o-phthalaldehyde and can disappear after several days. In addition, grey dyeing with different depths is often generated at the positions of a water tank, an operation table top, a work clothes and the like, the grey dyeing on the surface of the skin and the surface of an object is difficult to remove, and great troubles are caused to medical workers with higher requirements on the cleanliness of the working environment.

The prior art has attempted to reduce the grey problem by replacing phthalaldehyde with other materials, such as IN2005KO00043A using a combination of isophthalaldehyde, terephthaldehyde, and o-phthalaldehyde; adding glyoxylic acid into o-phthalaldehyde in JP 2008007408A; EP1559435A1 discloses novel fungicidal compositions containing halogenated benzaldehyde compounds, but toxicity of the novel substances, solubility of the novel compositions, stability and fungicidal property are all factors to be considered, and the formula in the method is not popularized in the market in time. It is also mentioned in the prior art that the addition of adjuvants to formulations of phthalaldehyde disinfectant compositions is desirable to avoid greying, for example CN105379712a mentions the addition of antioxidants to the formulation which, although it is claimed to avoid disinfectant greying problems, in fact the addition of antioxidants "prevents phthalaldehyde from oxidative failure" (see paragraph 0015 of the specification) enhances the stability of phthalaldehyde which is unavoidable given that the aldehyde group remains active. The disinfectant is prepared by adding quaternary ammonium salt disinfectant into CN108552173A, adding quaternary ammonium salt disinfectant into CN114916545A, compounding ferulic acid and boric acid solution to serve as a synergist, wherein both the disinfectant and the boric acid solution are compound disinfectants, quaternary ammonium salt is high in price and easy to foam, defoaming agents are required to be added into a formula, the generation of grey stain cannot be really inhibited, and only the reduction is achieved to a certain extent, so that the cleaning effect of the quaternary ammonium salt is possibly depended on.

In view of the above, the invention provides a method for designing and preparing a disinfectant solution capable of effectively reducing the gray stain of o-phthalaldehyde.

Disclosure of Invention

The invention provides an o-phthalaldehyde disinfectant and a preparation method thereof, and aims to reduce or eliminate the problem of adhesion of ash stain on an object surface of the o-phthalaldehyde disinfectant.

In order to achieve the purpose, the phthalic dicarboxaldehyde disinfectant adopts the technical scheme that: an o-phthalaldehyde disinfectant is innovative in that: the formula of the disinfectant consists of the following components in percentage by mass:

the chelating agent is at least one of ethylenediamine tetraacetic acid, disodium ethylenediamine tetraacetic acid, citrate, pyrophosphate and thiosulfate.

The dispersing agent is at least one of salicylic acid, polyethylene glycol, 1,3-butanediol, sodium tripolyphosphate and fatty acid polyglycol ester.

The buffer is at least one of ammonium acetate, ammonium chloride, phosphate, carbonate and sodium thiosulfate.

The relevant content in the above technical solution is explained as follows:

1. in the scheme, the o-phthalaldehyde is o-phthalaldehyde produced by Jiuquan Yajia chemical company Limited and is used as a main action component of the disinfectant.

2. In the scheme, the citrate is sodium citrate or potassium citrate.

3. In the above scheme, the pyrophosphate is sodium pyrophosphate or potassium pyrophosphate.

4. In the above scheme, the thiosulfate is a sodium thiosulfate salt or a potassium thiosulfate salt.

5. In the above scheme, the phosphate is a sodium phosphate salt or a potassium phosphate salt.

6. In the above scheme, the carbonate is sodium carbonate salt or potassium carbonate salt.

7. In the above scheme, the ratio of the chelating agent to the buffer is 2:1-1:50, the optimal mixture ratio is 1:5, use.

In order to achieve the purpose, the preparation method of the o-phthalaldehyde disinfectant adopts the technical scheme that: a preparation method of an o-phthalaldehyde disinfectant is characterized by comprising the following steps: according to the formula (components and content) of the o-phthalaldehyde disinfectant, the preparation method comprises the following steps:

preparation of solution A: adding pure water with the water content of 12.5 +/-0.5% into a container, and heating to 60-70 ℃; adding 0.6 percent of o-phthalaldehyde in the total amount of the formula into the container, and stirring at the temperature of 60-70 ℃ until the o-phthalaldehyde is completely dissolved to obtain solution A for later use;

and (3) preparation of a liquid B: adding the rest pure water into another reaction vessel, adding a chelating agent, hydroxyethylidene diphosphonic acid and a dispersing agent according to the formula content into the reaction vessel, and stirring for 50 +/-15 min to obtain a solution B for later use;

preparing an o-phthalaldehyde disinfectant: mixing and stirring the dissolved solution A and the solution B, reacting for 10-30min, adding a buffering agent with the formula content, stirring for 10 +/-5 min, adjusting the pH value to 8.5-9.0, and stirring for 30 +/-10 min to obtain the o-phthalaldehyde disinfection solution.

The mechanism and effect of the present invention are explained as follows: the speed of generating grey dye of the o-phthalaldehyde disinfectant liquid sold in the market at present is generally about 30s through tests, the speed of generating the grey dye of the o-phthalaldehyde disinfectant liquid is basically greater than 1min and 30s, the o-phthalaldehyde disinfectant liquid can effectively prevent the grey dye from being attached to the surface of an article after being generated, still has a high-level disinfection effect for four hours, can clean an endoscope more thoroughly, and ensures the working environment and the personal safety of medical care personnel.

In fact, "grey dyeing" is unavoidable in view of the disinfection mechanism of phthalaldehyde. The 'grey dyeing' usually occurs by the covalent crosslinking of a compound with aldehyde group and a compound with amino group through condensation of aldehyde group and imino group into Schiff base, the reaction rate of the covalent crosslinking is high, the generated Schiff base quickly dyes water tanks, wall surfaces, operation table surfaces, endoscope cleaning machines and the like, is difficult to remove, and the coloring is more obvious and firm as the time is prolonged. In the prior art, after the endoscope is disinfected by the o-phthalaldehyde, "grey dyeing" needs to be treated, so that the cost of disinfection is increased. The aim of the invention is not to eliminate the "grey stain", but to reduce or eliminate the adhesion of the grey stain of the o-phthalaldehyde disinfectant to the surface of the object. In order to solve the problem, the invention discovers that the phthalic dicarboxaldehyde disinfectant is adjusted within a certain pH value range, so that the generation speed of grey dye can be effectively reduced, and after the phthalic dicarboxaldehyde disinfectant is added with hydroxyethylidene phosphoric acid in a proper proportion, the covalent crosslinking reaction rate of aldehyde groups and imino groups condensed into Schiff base can be reduced, and stable complex compounds can be formed with various metal ions such as iron, copper, aluminum, zinc and the like. Experimental detection shows that after the endoscope is disinfected and cleaned by the phthalaldehyde disinfectant, the endoscope is obviously dark brown filiform grey-dyed in cleaning residual liquid, but the surfaces of the endoscope and a cleaning soaking pool are free from ash-dyed, and even if grey-dyed areas occur in disinfectant-free soaking areas such as an operation table, the endoscope is easy to wipe clean. In conclusion, the invention has substantial contribution and remarkable effect on reducing or removing the adhesion of the grey dye of the o-phthalaldehyde disinfectant on the surface of an object, and is unobvious to the technical personnel in the field, so that the invention has prominent substantial characteristics and remarkable technical progress.

Detailed Description

All experimental procedures used in the following examples are conventional unless otherwise specified. Materials, reagents and the like used in the following examples are commercially available unless otherwise specified. The o-phthalaldehyde is o-phthalaldehyde produced by JIAOQUANJIAK CHEMICAL CO.

The invention is further described below with reference to the following examples:

example 1: phthalic dicarboxaldehyde disinfectant and preparation method thereof

The formula of the o-phthalaldehyde disinfectant is shown in the following table:

salicylic acid in the formula is used as a synergist and a dispersant.

The preparation method of the o-phthalaldehyde disinfectant comprises the following steps:

preparation of solution A: 12.5g of pure water was taken in a vessel and heated to 60 ℃. 0.6g of o-phthalaldehyde was added to the vessel, and stirred at 60 ℃ until the o-phthalaldehyde was completely dissolved to obtain solution A for use. In the preparation process, the adding amount of the raw material of the o-phthalaldehyde is fixed every time, the amount of the o-phthalaldehyde is lost after mixing, and the concentration of the o-phthalaldehyde detected in the finally obtained disinfectant is between 0.5 and 0.6 percent.

And (3) preparation of a liquid B: adding the residual amount of pure water into another reaction vessel, sequentially adding 0.1g of ethylenediamine tetraacetic acid, 10g of hydroxyethylidene diphosphonic acid and 0.1g of salicylic acid into the reaction vessel, and stirring for 50min to obtain liquid B for later use.

Preparing an o-phthalaldehyde disinfectant: and injecting the dissolved solution A into a reaction vessel of the solution B, mixing and stirring the solution A and the solution B, reacting the solution A for 30min, adding 1.0g of disodium hydrogen phosphate, stirring the solution A for 10min, adjusting the pH value to 8.5 (the term of adjusting the pH value refers to adjusting the pH value of the original solution to 8.5 after adding sodium dihydrogen phosphate), and stirring the solution A for 30min to obtain the o-phthalaldehyde disinfection solution.

Example 2: phthalic dicarboxaldehyde disinfectant and preparation method thereof

preparation of solution A: 12.5g of purified water was taken in a vessel and heated to 70 ℃. 0.6g of o-phthalaldehyde was added to the vessel, and stirred at 70 ℃ until the o-phthalaldehyde was completely dissolved to obtain solution A for use.

And (3) preparation of a liquid B: adding the residual amount of pure water into another reaction vessel, sequentially adding 2g of disodium ethylene diamine tetraacetate, 5g of hydroxyethylidene diphosphonic acid and 2.5g of polyethylene glycol into the reaction vessel, and stirring for 50min to obtain liquid B for later use.

Preparing an o-phthalaldehyde disinfectant: and (2) injecting the dissolved solution A into a reaction vessel of the solution B, mixing and stirring the solution A and the solution B, reacting the solution A for 10min, adding 5g of sodium carbonate, stirring the solution A for 10min, adjusting the pH value to 8.6 (the term of adjusting means that the pH value of the original solution is adjusted to 8.6 after the sodium carbonate is added), and stirring the solution A for 30min to obtain the o-phthalaldehyde disinfection solution.

Example 3: phthalic dicarboxaldehyde disinfectant and preparation method thereof

in the formula, 1,3 butanediol is used as a cosolvent and a dispersant, and salicylic acid is used as a synergist and a dispersant.

preparation of solution A: 12.5g of pure water was taken in a vessel and heated to 64 ℃. 0.6g of o-phthalaldehyde was added to the vessel and stirred at 64 ℃ until the o-phthalaldehyde was completely dissolved to obtain solution A for use.

And (3) preparation of liquid B: adding the residual amount of pure water into another reaction vessel, sequentially adding 0.5g of ethylenediamine tetraacetic acid, 1g of hydroxyethylidene diphosphonic acid, 2g of 1,3 butanediol and 0.2g of salicylic acid into the reaction vessel, and stirring for 50min to obtain a solution B for later use.

Preparing an o-phthalaldehyde disinfectant: and (2) injecting the dissolved solution A into a reaction vessel of the solution B, mixing and stirring the solution A and the solution B, reacting for 20min, then adding 1g of ammonium chloride, stirring for 10min, adjusting the pH value to 8.7 (the term of adjusting means that the pH value of the original solution is adjusted to 8.7 after the ammonium chloride is added), and stirring for 30min to obtain the o-phthalaldehyde disinfectant.

Example 4: phthalic dicarboxaldehyde disinfectant and preparation method thereof

And (3) preparation of a liquid B: adding the rest amount of pure water into another reaction vessel, sequentially adding 1g of disodium ethylene diamine tetraacetate, 5g of hydroxyethylidene diphosphonic acid and 2.5g of polyethylene glycol into the reaction vessel, and stirring for 50min to react to obtain liquid B for later use.

Preparing an o-phthalaldehyde disinfectant: and (2) injecting the dissolved solution A into a reaction vessel of the solution B, mixing and stirring the solution A and the solution B, reacting the solution A for 10min, adding 5g of sodium carbonate, stirring the solution A for 10min, adjusting the pH value to 9.0 (the term of adjusting means that the pH value of the original solution is adjusted to 9.0 after the sodium carbonate is added), and stirring the solution A for 30min to obtain the o-phthalaldehyde disinfection solution.

Comparative example 1 an o-phthalaldehyde disinfectant and a preparation method thereof

This embodiment is different from embodiment 1 in that: the raw material formula of the o-phthalaldehyde disinfectant does not contain hydroxyethylidene diphosphonic acid, and other contents and preparation methods are the same as those in example 1. The description will not be repeated here.

Comparative example 2: phthalic dicarboxaldehyde disinfectant and preparation method thereof

This embodiment differs from embodiment 2 in that: the contents and preparation method were the same as in example 2 without adding sodium carbonate. The description will not be repeated here.

Comparative example 3: phthalic dicarboxaldehyde disinfectant and preparation method thereof

This embodiment differs from embodiment 2 in that: sodium carbonate in excess was added to adjust the pH to greater than 9.0, and the rest of the contents and preparation were the same as in example 2. The description is not repeated here.

The following are the results of experiments and tests of the o-phthalaldehyde disinfection solutions of the examples and comparative examples of the present invention:

as can be seen from the test results in the above table, the concentrations of phthalaldehyde in the disinfectant liquids of the examples and comparative examples were in the range of 0.57% to 0.60% (by mass), which are relatively comparable. In terms of pH, the pH values of the other examples and comparative examples, except for comparative example 2 and comparative example 3, fell within the range of 8.5 to 9.0 and were weakly alkaline. While comparative example 2 had a pH of 7.2, which was less than the upper pH limit of 8.5 required by the present invention, which resulted from the absence of sodium carbonate. Comparative example 3 had a pH of 9.3, which was greater than the upper pH limit of 9.0 required by the present invention, which was also the result of adding excess sodium carbonate. From the simulated gray-dyeing time, examples 1-4 and comparative example 3 are relatively long, falling between 1min30s (1 min30 s) and 1min50 s (1 min50 s). While comparative examples 1 and 2 were relatively short in time, 56s (56 seconds) and 32s (32 seconds) in that order. From the viewpoint of the minimum time required for high-level sterilization, examples 1 to 4 were at 3h30 min (3 hr 30 min) to 4h (4 hr), while comparative examples 1 to 3 were at 5h, 7h and 7h in this order, which is relatively long in the minimum time required for high-level sterilization of the comparative examples and shorter in the minimum time required for high-level sterilization of the examples. The chelating agent and buffer ratio in example 2 was adjusted to give the best results in example 4 based on the grey dye generation time versus the high level of disinfection minimum time, at which point the chelating agent and buffer ratio was 1:5, use. From the viewpoint of simulating the endoscopic cleaning gray-stain adhesion, examples 1 to 4 were ashless adhesion, comparative examples 1 and 2 were gray-stain adhesion, and comparative example 3 was ashless adhesion but the o-benzene evolution phenomenon occurred.

The test method corresponding to the detection result is as follows:

1. the method for testing the concentration of the o-phthalaldehyde comprises the following steps: high performance liquid chromatography (the instrument model used is Agilent 1260 definition II).

2. The high-level sterilization and disinfection method comprises the following steps: the disinfection technical specification is 2002 suspension method, and the strain is black variant spore of bacillus subtilis.

3. The simulated grey dye generation experimental method comprises the following steps: simulation is carried out in an endoscope cleaning simulation laboratory, and the residue of the human tissue of the endoscope is simulated by adding animal tissue.

With respect to the above embodiments, possible variations of the present invention are described below:

1. in the above examples 1-4, only ethylenediaminetetraacetic acid or disodium ethylenediaminetetraacetate was selected as the chelating agent. The invention is not limited to the above, and actually, the chelating agent of the invention can be one or a combination of two or more of ethylenediamine tetraacetic acid, disodium ethylenediamine tetraacetic acid, citrate, pyrophosphate and thiosulfate, and can achieve the same or similar technical effects. The examples are not to be construed as limiting the space. As would be understood and accepted by those skilled in the art.

2. In examples 1-4 above, the dispersant was selected from salicylic acid only, or polyethylene glycol, or a combination of 1,3 butanediol and salicylic acid. The invention is not limited to the above, and actually, the dispersant of the invention can be one or a combination of two or more of salicylic acid, polyethylene glycol, 1,3 butanediol, sodium tripolyphosphate and fatty acid polyglycol ester, and can achieve the same or similar technical effects. The examples are not to be construed as limiting the space. As would be understood and accepted by those skilled in the art.

3. In the above examples 1-4, the buffer is selected from sodium dihydrogen phosphate, sodium carbonate, or ammonium chloride. However, the present invention is not limited thereto, and in fact, the buffer of the present invention may be one or a combination of two or more of ammonium acetate, ammonium chloride, phosphate, carbonate and sodium thiosulfate, which can achieve the same or similar technical effects. The examples are not to be construed as limiting the space. As would be understood and accepted by those skilled in the art.

4. In the above examples 1 to 4, sodium dihydrogen phosphate was used as the phosphate, and sodium carbonate was used as the carbonate, and these were sodium salts. The invention is not limited thereto, and the corresponding potassium salts may also be used. For example, the carbonate is sodium carbonate or potassium carbonate; the phosphate is sodium phosphate or potassium phosphate; the citrate is sodium citrate or potassium citrate; the pyrophosphate is sodium pyrophosphate or potassium pyrophosphate; the thiosulfate is sodium thiosulfate or potassium thiosulfate. As would be understood and accepted by those skilled in the art.

The above embodiments are merely illustrative of the technical ideas and features of the present invention, and the purpose thereof is to enable those skilled in the art to understand the contents of the present invention and implement the present invention, and not to limit the protection scope of the present invention. All equivalent changes and modifications made according to the spirit of the present invention should be covered within the protection scope of the present invention.

Claims

1. An o-phthalaldehyde disinfectant is characterized in that: the disinfectant consists of the following components in percentage by mass:

0.5 to 0.6 percent of o-phthalaldehyde;

0.1% -2% of chelating agent;

1% -10% of hydroxyl ethylidene diphosphonic acid;

0.1 to 2.5 percent of dispersant;

1% -5% of a buffering agent;

the balance of pure water;

the chelating agent is at least one of ethylenediamine tetraacetic acid, disodium ethylenediamine tetraacetic acid, citrate, pyrophosphate and thiosulfate;

the dispersing agent is at least one of salicylic acid, polyethylene glycol, 1,3-butanediol, sodium tripolyphosphate and fatty acid polyethylene glycol ester;

2. The phthalaldehyde disinfectant liquid according to claim 1, wherein: the citrate is sodium citrate or potassium citrate.

3. The phthalaldehyde disinfectant solution according to claim 1, wherein: the pyrophosphate is sodium pyrophosphate or potassium pyrophosphate.

4. The phthalaldehyde disinfectant liquid according to claim 1, wherein: the thiosulfate is sodium thiosulfate or potassium thiosulfate.

5. The phthalaldehyde disinfectant liquid according to claim 1, wherein: the phosphate is sodium phosphate or potassium phosphate; the carbonate is sodium carbonate salt or potassium carbonate salt.

6. The phthalaldehyde disinfectant liquid according to claim 1, wherein: the proportion of the chelating agent to the buffering agent is 2:1-1:50 are used.

7. A preparation method of an o-phthalaldehyde disinfectant is characterized by comprising the following steps: the disinfectant fluid formulation of claim 1, which is prepared by the following steps:

preparing an o-phthalaldehyde disinfectant: mixing and stirring the dissolved solution A and solution B, reacting for 10-30min, adding a buffering agent with the formula content, stirring for 10 +/-5 min, adjusting the pH value to 8.5-9.0, and stirring for 30 +/-10 min to obtain the o-phthalaldehyde disinfectant.