A cleaning composition and detergent and application thereof
By using a cleaning composition composed of Sipan, Tween and fatty alcohol polyoxyethylene ether, a cleaning agent that can effectively clean the pharmaceutical production line equipment at room temperature was prepared, which solved the problems of low automation and blockage caused by Vaseline solidification in the prior art, and achieved efficient and environmentally friendly cleaning effect.
Patent Information
- Application Number
- CN202411943463.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-27
- Publication Date
- 2025-04-04
Smart Images
Figure CN119752551A_ABST
Abstract
Description
Technical Field
[0001] The present application relates to the technical field of cleaning agents, and in particular to a cleaning composition and a cleaning agent and applications thereof. Background Art
[0002] Mineral oil is a mixture obtained by fractionation of crude oil, and its main component is a mixture of hydrocarbons. In the field of pharmaceutical production, mineral oil (such as vaseline, paraffin, etc.) is often added as a pharmaceutical excipient as an ointment base or lubricant. Among the mineral oils used as pharmaceutical excipients, vaseline has the most extensive application scenarios.
[0003] In the process of drug production, mineral oil is very likely to leave residues in the production equipment due to its properties and solubility. The existing cleaning process of the production line of drugs using mineral oil or similar substances as ointment matrix is usually to use a large amount of hot water above 80°C to wash the inner wall of the equipment, so that the ointment matrix remaining on the inner wall melts at high temperature and is discharged into the sewage pipe with the cleaning waste liquid.
[0004] Since vaseline is mostly washed away by water because it melts at high temperature, when the cleaning waste liquid reaches the pipeline or discharge port, vaseline will precipitate because the water temperature drops to room temperature. Vaseline solidifies in the drainage pipeline and adheres to the inner wall of the drainage pipe, which easily causes the drainage pipeline to be blocked. Therefore, it is necessary to collect the cleaning water into a waste liquid tank with a certain volume before discharge, and then manually filter out the vaseline before continuing to discharge. In some cases, it is also necessary to add a screen to the discharge port to intercept the vaseline that has not been completely filtered out. Therefore, the existing method has a low degree of automation, and the filtration of vaseline and the replacement of the screen must be done manually.
[0005] Moreover, in the process of drug production, there is often a situation of co-production of products. Since conventional detergents have a poor cleaning effect on vaseline, a large amount of detergents need to be used, which not only increases the cost, but also a large amount of detergents are easily left on the pipe wall and brought into the next batch of drugs produced. Therefore, the existing method not only wastes a large amount of water resources, but also has a poor cleaning effect, especially the corners of the pipeline, welds, etc. are easy to retain the precipitated vaseline. The residual vaseline, together with the medicinal active ingredients it carries, is likely to be brought into the next production, affecting the quality of the next batch of products, and not meeting the requirements of production management.
[0006] In order to minimize the contamination between products produced on the same line and ensure the safety, effectiveness and quality of drugs, the cleaning of mineral oil residues on such production lines has become a key concern and an issue that needs to be urgently addressed in drug production quality management.
[0007] It can be seen that there is an urgent need for a cleaning agent that is clean, environmentally friendly, practical, and meets the needs of industrialized pharmaceutical production to clean the production line of pharmaceuticals using mineral oil or other substances of similar properties as ointment bases. Summary of the invention
[0008] In order to solve the above problems, the present application provides a cleaning composition and a cleaning agent and their application. The cleaning agent has a good cleaning effect on the production line of medicines with mineral oil or other substances of similar properties as ointment matrix. The ointment matrix of the cleaning waste liquid will not solidify at room temperature, which effectively solves the drawbacks of the existing cleaning of mineral oil medicine production lines.
[0009] This application adopts the following technical solutions:
[0010] In a first aspect, the present application provides a cleaning composition comprising the following components in parts by mass:
[0011] Span 16.5-52;
[0012] Tween 12-30 parts;
[0013] 25-72 parts of fatty alcohol polyoxyethylene ether,
[0014] The Span includes Span 20 and / or Span 40, the Tween includes Tween 60 and / or Tween 80, and the fatty alcohol polyoxyethylene ether includes AEO-3 and / or AEO-5.
[0015] Optionally, the cleaning composition further comprises 0-2 parts by mass of sodium dodecylbenzene sulfonate.
[0016] Optionally, the cleaning composition further comprises 0.5-2 parts of an alkaline regulator by weight. The main function of the alkaline regulator is to remove stains such as free acids and proteins that may be introduced during the production of drugs, and at the same time loosen and disperse precipitates to achieve a synergistic cleaning effect. The alkaline regulator can be a preparation with strong alkalinity, high safety, and no volatility.
[0017] Optionally, the alkaline regulator is selected from one or more of potassium hydroxide, sodium hydroxide or sodium bicarbonate.
[0018] Optionally, the cleaning composition comprises the following components in parts by mass:
[0019]
[0020]
[0021] In a second aspect, the present application also provides a cleaning agent, comprising any of the above-mentioned cleaning compositions and water.
[0022] Optionally, the mass volume concentration of the cleaning agent is not higher than 0.5% (w / v). The concentration unit % refers to the mass of the cleaning composition contained in every 100 ml of the cleaning agent, and the mass unit of the cleaning composition is gram. The mass volume concentration of the cleaning agent of 0.5% (w / v) means that 0.5g of the cleaning composition is added to every 100ml of the cleaning agent solution.
[0023] In a third aspect, the present application also provides the use of the above-mentioned cleaning agent in cleaning drug residues, especially in cleaning drug ointment matrix residues, including cleaning of equipment in a drug production line, such as production tanks and / or pipelines. Optionally, the production tank includes a mixing tank and / or a blending tank.
[0024] Optionally, the drug is a drug containing an ointment base, and optionally, the drug is an ointment preparation, a gel preparation or a suppository. Optionally, the ointment base includes the oily base in the ointment preparation, the natural gum base in the gel preparation or the oily base in the suppository, etc.; preferably, the oily base in the ointment preparation includes one or more of vaseline, liquid paraffin, lanolin, ceresin, beeswax, saturated and unsaturated fatty acid esters, vegetable oils, and dimethyl silicone oil; preferably, the natural gum base in the gel preparation is selected from one or more of pectin, alginic acid, and guar gum; preferably, the oily base in the suppository is selected from one or more of cocoa butter, semi-synthetic or fully synthetic fatty acid glycerides.
[0025] Optionally, the cleaning agent is used for cleaning at 60°C-70°C.
[0026] Specifically, the cleaning method of the ointment medicine production line, the equipment of the production line includes production tanks (such as mixing tanks, preparation tanks) and pipelines, and the cleaning method includes: a cleaning agent immersion cleaning step, using the above-mentioned cleaning agent to immerse and clean the mixing tank; a cleaning agent circulation flushing step, using the above-mentioned cleaning agent to circulate and flush the production tanks and pipelines.
[0027] The cleaning agent soaking cleaning steps include:
[0028] Prepare 75%-85% of the above cleaning agent in the mixing tank and inject it into the production tank; heat it to 60℃-70℃ and inject it into the production tank, and continue to inject water to 75%-85% of the capacity of the production tank;
[0029] The temperature in the production tank is heated and maintained at 60° C.-70° C., and after stirring and soaking for at least 20 minutes, the production tank is emptied.
[0030] The cleaning agent circulation cleaning steps include:
[0031] Prepare 15%-25% of the above cleaning agent in the production tank capacity; dissolve the prepared flushing cleaning agent in 15%-25% of the water in the production tank capacity to form the flushing cleaning agent;
[0032] Heat the rinse cleaning agent to 60℃-70℃;
[0033] Use a flushing and cleaning agent at 60℃-70℃ to circulate and flush the production tanks for 20-30 minutes, and circulate and flush the pipelines for 10-20 minutes.
[0034] This application has the following advantages:
[0035] The cleaning composition proposed in the present application is highly safe and has a good cleaning effect on drug residues, especially ointment preparations, by controlling the content ratio of the components, especially vaseline-like substances, and can be used for cleaning ointment residues in drug production lines.
[0036] The cleaning agent proposed in this application has a good cleaning effect on oil and ointment residues. By using a cleaning agent with a mass volume concentration (w / v) not exceeding 0.5%, an excellent cleaning effect can be achieved, which greatly reduces the risk of cleaning agent residues, greatly reduces the amount of cleaning agent used, is easy to use, and reduces cleaning costs.
[0037] In terms of cleaning drug residues, the cleaning agent of the present application wraps ointment preparations in droplets by emulsifying the cleaning agent, and will not precipitate even when the temperature drops to room temperature, which not only eliminates the risk of residual substances being brought into the next production, but also saves the trouble of manually collecting and filtering ointments and replacing filters. The cleaning agent of the present application has high practicality, is pollution-free, and saves energy. BRIEF DESCRIPTION OF THE DRAWINGS
[0038] Figure 1 This is a schematic diagram of the cleaning method of Experimental Example 5. DETAILED DESCRIPTION
[0039] The exemplary embodiments of the present application will be described in more detail below. However, it should be understood that the present application can be implemented in various forms and should not be limited by the embodiments set forth herein. On the contrary, these embodiments are provided to enable a more thorough understanding of the present application and to enable the scope of the present application to be fully communicated to those skilled in the art.
[0040] A cleaning composition comprising the following components in parts by mass:
[0041] Span 16.5-52;
[0042] Tween 12-30 parts;
[0043] 25-72 parts of fatty alcohol polyoxyethylene ether.
[0044] In this application, Span refers to Span series products, and Twain refers to Twain series products.
[0045] The Span includes Span 20 and / or Span 40, the Tween includes Tween 60 and / or Tween 80, and the fatty alcohol polyoxyethylene ether includes AEO-3 and / or AEO-5.
[0046] The above compound compounding makes the interfacial film formed by the surfactant at the oil / water interface have a more matching natural curvature with the oil droplet and a higher bending stiffness, thus having better stability. In addition, the above compound compounding can improve the solubilization ability and reduce the amount of a single type of surfactant, which complies with the regulatory requirements of the "Guidelines for Quality Risk Management of Co-production of Pharmaceuticals".
[0047] Wherein, by mass parts, the cleaning composition comprises the following components:
[0048] Span 20: 16-48 parts, preferably 24-30 parts, more preferably 24 parts;
[0049] Span 40: 0.5-4 parts, preferably 1-2 parts, more preferably 2 parts;
[0050] Tween 60: 4-10 parts, preferably 6-8 parts, more preferably 8 parts;
[0051] Tween 80: 8-20 parts, preferably 12-16 parts, more preferably 16 parts;
[0052] AEO-3: 1-8 parts, preferably 2-4 parts, more preferably 4 parts;
[0053] AEO-5: 24-64 parts, preferably 32-48 parts, more preferably 32 parts;
[0054] Sodium dodecylbenzene sulfonate: 0-2 parts, preferably 1-1.5 parts, more preferably 1 part;
[0055] Potassium hydroxide: 0.5-2 parts, preferably 1-1.5 parts, more preferably 1 part.
[0056] A cleaning agent comprises any of the above cleaning compositions and water, wherein the water can be water available in a pharmaceutical production workshop, such as purified water or water for injection. The cleaning composition is dissolved in water in proportion and mixed evenly to obtain a cleaning agent. The mass volume concentration of the cleaning agent is not higher than 0.5% (w / v), and can specifically be 0.5% (w / v), 0.45% (w / v), 0.4% (w / v), 0.35% (w / v), 0.3% (w / v), 0.25% (w / v) or 0.2% (w / v), etc.
[0057] The above-mentioned cleaning agent is used in cleaning drug residues, such as cleaning production tanks, pipelines, containers and other parts containing drug residues in drug production lines. The ointment matrix of the drug may include (1) oily matrix in ointment preparations: vaseline, liquid paraffin, lanolin, ceresin, beeswax, saturated and unsaturated fatty acid esters, vegetable oils, dimethyl silicone oil, etc.; (2) natural gum matrix in gel preparations: pectin, alginic acid, guar gum, etc.; (3) oily matrix in suppositories: cocoa butter, semi-synthetic or fully synthetic fatty acid glycerides. The cleaning agent proposed in the present application has a good cleaning effect on the above-mentioned substances, among which the cleaning effect on vaseline substances, which are the most difficult to clean among these matrices, is high, and can reach more than 92% under preferred conditions. The cleaning agent of the present application can be cleaned at 60°C-70°C.
[0058] The technical solution of the present application is further illustrated below with reference to embodiments.
[0059] Experimental Example 1
[0060] Examples 1-1 to 1-14 were set up to test the cleaning efficacy by taking vaseline, which is the most difficult to clean among the drug matrices, as an example. The component ratios and cleaning efficacy thereof are shown in Table 1.
[0061] Add an appropriate amount of purified water to a 1000ml beaker and heat it to 60°C with a water bath. Weigh 5g of the cleaning composition formulated according to the embodiments in Table 1 and dissolve it in purified water. Add the remaining purified water until the total amount reaches 1000ml, then the mass volume concentration of the cleaning agent is 0.5% (w / v). Stir with a magnetic stirrer for 10min at a speed of 900R / min to mix the cleaning agent evenly. Use a 10×10cm 316 steel plate to simulate the inner wall of the production tank. The stainless steel plate weighs 400g and is coated with 4g of white vaseline (about 0.5mm thick) on one side. Place the stainless steel plate in a beaker to prevent vaseline from getting on the outer wall or mouth of the beaker. The magnetic stirrer is on the side without vaseline, and stir with a magnetic stirring simulated stirring paddle at a speed of 500R / min for 10min. After cleaning the stainless steel plate, take it out, rinse it gently with purified water, wash off the foam remaining on the sample, dry it naturally, weigh it, and the reduced mass is the mass of the vaseline washed off.
[0062] Here, cleaning effectiveness = (coating amount - residual amount) / coating amount × 100%.
[0063] Table 1:
[0064]
[0065] From the results shown in Table 1 above, it can be seen that:
[0066] The cleaning agents of Examples 1-1, 1-2, 1-4, 1-6, 1-8 to 1-14 of the present application using Span 20 and / or Span 40, Tween 60 and / or Tween 80, AEO-3 and / or AEO-5 have significantly higher cleaning effectiveness against vaseline than Examples 1-3, 1-5, and 1-7 using Span 80, Tween 20, and AEO-9. The cleaning effects of Examples 1-8 to 1-14, which have a combination of Span 20 and Span 40, Tween 60 and Tween 80, or AEO-5 and AEO-3, are better than those of Examples 1-1, 1-2, 1-4, and 1-6, which use Span 20 or Span 40, Tween 60 or Tween 80, AEO-3, or AEO-5. The cleaning effect of Example 1-14, which uses a combination of Span 20 and Span 40, Tween 60 and Tween 80, and AEO-5 and AEO-3, is the best, reaching more than 90%. The cleaned solutions of Examples 1-1, 1-2, 1-4, 1-6, 1-8 to 1-14 are placed at room temperature to form uniformly dispersed emulsions without precipitation and good fluidity.
[0067] Experimental Example 2
[0068] Examples 2-1 to 2-40 were set up to test the cleaning efficacy using vaseline, which is the most difficult to clean among the pharmaceutical matrices, as an example. The component ratios and cleaning efficacy thereof are shown in Table 2.
[0069] Add an appropriate amount of purified water to a 1000ml beaker and heat it to 60°C with a water bath. Weigh 5g of the cleaning composition formulated according to the embodiments in Table 2 and dissolve it in purified water. Add the remaining purified water until the total amount reaches 1000ml, then the mass volume concentration of the cleaning agent is 0.5% (w / v). Stir with a magnetic stirrer for 10min at a speed of 900R / min to mix the cleaning agent evenly. Use a 10×10cm 316 steel plate to simulate the inner wall of the production tank, the stainless steel plate weighs 400g, and is coated with 4g of white vaseline (about 0.5mm thick) on one side. Place the stainless steel plate in a beaker to prevent vaseline from getting on the outer wall or mouth of the beaker. The magnetic stirrer is on the side without vaseline, and stir with a magnetic stirring simulated stirring paddle at a speed of 500R / min for 10min. After cleaning the stainless steel plate, take it out, rinse it gently with purified water, wash off the foam remaining on the sample, dry it naturally, weigh it, and the reduced mass is the mass of the vaseline washed off.
[0070] In addition, the mass fractions of each component in the cleaning agent in Experimental Example 2 were prepared. Referring to Table 2, the total mass of each cleaning agent is 5g, that is, the total mass of Span 20, Span 40, Tween 60, Tween 80, AEO-3, AEO-5, sodium dodecyl sulfate, and alkaline pH regulator is 5g. In Experimental Example 2, the alkaline regulator uses potassium hydroxide. For each, the total mass 5g is divided by the total mass fraction to obtain the mass corresponding to each mass fraction, and each component is weighed according to its corresponding mass fraction.
[0071] For example, for 2-1 in Experimental Example 2, Span 20 is 0 parts, Span 40 is 2 parts, Tween 60 is 8 parts, Tween 80 is 16 parts, AEO-3 is 4 parts, AEO-5 is 32 parts, sodium dodecyl sulfate is 1 part, and potassium hydroxide is 1 part, so the total mass parts are 64 parts. The mass corresponding to each mass part is 0.0781g by dividing the total mass 5g by the total mass parts 64. Then, the corresponding mass of each component is calculated according to its corresponding mass parts, Span 20 is 0g, Span 40 is 0.1563g, Tween 60 is 0.625g, Tween 80 is 1.25g, AEO-3 is 0.3125g, AEO-5 is 2.5g, sodium dodecyl sulfate is 0.0781g, and potassium hydroxide is 0.0781g.
[0072] Add an appropriate amount of purified water to a 1000ml beaker and heat it to 60°C in a water bath. Weigh 0.1563g Span 40, 0.625g Tween 60, 1.25g Tween 80, 0.3125g AEO-3, 2.5g AEO-5, 0.0781g sodium dodecyl sulfate and 0.0781g potassium hydroxide in turn and dissolve them in purified water. Add the remaining amount of purified water to a total amount of 1000ml to prepare a cleaning agent with a mass volume concentration of 0.5% (w / v).
[0073] Experimental Example 2 In other embodiments, the mass of each component in 5g of cleaning agent is calculated according to the above method, so it is not repeated here.
[0074] In Experimental Example 2, the selection of cleaning agents and their cleaning effectiveness are shown in Table 2 below.
[0075] Table 2:
[0076]
[0077]
[0078] According to the results shown in Table 2 above, it can be seen that:
[0079] Examples 2-1 to 2-6 in Table 2 show the cleaning efficacy of the cleaning solution on vaseline when the mass fraction of Span 20 is 0, 16, 24, 30, 48 and 96. When Span 20 is 16-48 mass fractions, the cleaning efficacy reaches more than 90%, which is better than that of Example 2-1 and Example 2-6 which are out of range; when Span 20 is 24-30 mass fractions, the effect is even better, and the cleaning efficacy reaches more than 92%.
[0080] Examples 2-3 and 2-7 to 2-11 in Table 2 show the cleaning efficacy of the cleaning solution on vaseline when the mass fraction of Span 40 is 0, 0.5, 1, 2, 4 and 8 parts. When Span 40 is 0.5-4 parts by mass, the cleaning efficacy reaches more than 90%, which is better than Examples 2-7 and 2-11 outside this range; among them, when Span 40 is 1-2 parts, the effect is even better, and the cleaning efficacy reaches more than 92%.
[0081] Examples 2-3 and 2-12 to 2-16 in Table 2 show the cleaning efficacy of the cleaning solution on vaseline when the mass fraction of Tween 60 is 0, 4, 6, 8, 10 and 16. When Tween 60 is 4-10 mass fractions, the cleaning efficacy reaches more than 90%, which is better than Examples 2-12 and 2-16 outside the range; when Tween 60 is 6-8 mass fractions, the effect is even better, and the cleaning efficacy reaches more than 92%.
[0082] Examples 2-3 and 2-17 to 2-21 in Table 2 show the cleaning efficacy of the cleaning solution on vaseline when the mass fraction of Tween 80 is 0, 8, 12, 16, 20 and 32 parts. When Tween 80 is 8-20 parts by mass, the cleaning efficacy reaches more than 90%, which is better than Examples 2-17 and 2-21 outside the range; among them, when Tween 80 is 12-16 parts, the effect is better, and the cleaning efficacy reaches more than 92%.
[0083] Examples 2-3 and 2-22 to 2-26 in Table 2 show the cleaning efficacy of the cleaning solution on vaseline when the mass fraction of AEO-3 is 0, 1, 2, 4, 8 and 16 parts. When AEO-3 is 1-8 parts by mass, the cleaning efficacy reaches more than 90%, which is better than that of Examples 2-22 and 2-26 outside the range; among them, when AEO-3 is 2-4 parts, the effect is even better, and the cleaning efficacy reaches more than 92%.
[0084] Potassium hydroxide: 0.5-2 parts, preferably 1-1.5 parts, more preferably 1 part.
[0085] Examples 2-3 and 2-27 to 2-31 in Table 2 show the cleaning efficacy of the cleaning solution on vaseline when the mass fraction of AEO-5 is 0, 24, 32, 48, 64 and 96 parts. When AEO-5 is 24-64 parts by mass, the cleaning efficacy reaches more than 90%, which is better than that of Examples 2-27 and 2-31 outside the range. Among them, when AEO-5 is 32-48 parts, the effect is even better, and the cleaning efficacy reaches more than 92%.
[0086] Examples 2-3 and 2-32 to 2-35 in Table 2 show the cleaning effect of the cleaning solution on vaseline when the mass fraction of sodium dodecylbenzene sulfonate is 0, 1, 1.5, 2 and 4 parts. When the mass fraction of sodium dodecylbenzene sulfonate is 0-2 parts, the cleaning effect reaches more than 90%, which is excellent; when the mass fraction of sodium dodecylbenzene sulfonate is 1-1.5 parts, the cleaning effect reaches more than 91%, which is even better.
[0087] Examples 2-3 and 2-36 to 2-40 in Table 2 show the cleaning efficacy of the cleaning solution on vaseline when the mass fraction of potassium hydroxide is 0, 0.5, 1, 1.5, 2 and 4 parts. When the mass fraction of potassium hydroxide is 0.5-2 parts, the cleaning efficacy reaches more than 90%, which is excellent; when the mass fraction of potassium hydroxide is 1-1.5 parts, the cleaning efficacy reaches more than 91%, which is even better.
[0088] The cleaned solution from 2-1 to 2-40 is placed at room temperature and becomes a uniformly dispersed emulsion with no precipitation and good fluidity.
[0089] Therefore, as a preferred embodiment, the cleaning composition comprises or consists of the following components in parts by mass:
[0090]
[0091] Referring to Example 2-3 of Table 2, when Span 20 is 24 parts, Span 40 is 2 parts, Tween 60 is 8 parts, Tween 80 is 16 parts, AEO-3 is 4 parts, AEO-5 is 32 parts, sodium dodecylbenzene sulfonate is 1 part, and potassium hydroxide is 1 part, the cleaning efficiency reaches 93.47%.
[0092] Therefore, as a most preferred embodiment, the cleaning composition comprises or consists of the following components by mass:
[0093]
[0094] That is, in the cleaning composition provided in the present application, the mass fraction of Span 20 is 12.7%-55.8%, preferably 22.9%-35.3%, and most preferably 27.3%; the mass fraction of Span 40 is 0.3%-7%, preferably 0.9%-2.5%, and most preferably 2.3%; the mass fraction of Tween 60 is 2.6%-16.7%, preferably 5.5%-9.9%, and most preferably 9.1%; the mass fraction of Tween 80 is 5.8%-30.3%, preferably 11.2%-19.3%, The most preferred amount is 18.2%; the mass fraction of AEO-3 is 0.7%-13.1%, preferably 1.8%-4.9%, and most preferably 4.5%; the mass fraction of AEO-5 is 21%-68.1%, preferably 33.7%-60.8%, and most preferably 36.4%; the mass fraction of sodium dodecylbenzene sulfonate is 0%-3.6%, preferably 0.9%-1.9%, and most preferably 1.1%; the mass fraction of potassium hydroxide is 0.3%-3.6%, preferably 0.9%-1.9%, and most preferably 1.1%.
[0095] Experimental Example 3
[0096] Each embodiment of Experimental Example 3 was set up to test the cleaning effectiveness. The cleaning agent configuration and testing process were the same as those of Experimental Example 1. The component ratio and cleaning effectiveness are shown in Table 3.
[0097] Table 3:
[0098] Serial number Span 20 Span 40 Twain 60 Twain 80 AEO-3 AEO-5 Residue(g) Cleaning effectiveness 3-1 16.5 0 12 0 25 0 0.64 84.00％ 3-2 52 0 30 0 72 0 0.59 85.25％ 3-3 52 0 30 0 8 64 0.56 86.00％ 3-4 52 0 10 20 8 64 0.53 86.75％ 3-5 0 16.5 0 12 0 25 0.62 84.50％ 3-6 16 0.5 0 12 0 25 0.51 87.25％ 3-7 16 0.5 0 12 1 24 0.46 88.50％ 3-8 0 52 0 30 0 72 0.61 84.75％
[0099] According to the results shown in Table 3 above, the cleaning effects of Examples 3-1 to 3-8 can reach more than 84%, proving that 16.5-52 parts by mass of Span 20 or Span 40, 12-30 parts by mass of Tween 60 or Tween 80, and 25-72 parts by mass of AEO-3 or AEO-5 all have good cleaning effects. The cleaned solutions of Examples 3-1 to 3-8 are placed at room temperature to form uniformly dispersed emulsions without precipitation and good fluidity.
[0100] Experimental Example 4
[0101] A method for cleaning an ointment medicine production line, wherein the production line includes production tanks and pipelines. The cleaning method comprises the following steps:
[0102] A cleaning agent soaking and cleaning step, using the cleaning agent proposed in this application to soak and clean the production tank;
[0103] The cleaning agent circulation flushing step uses the cleaning agent proposed in this application to circulate and flush the production tanks and pipelines.
[0104] The cleaning agent soaking cleaning steps include:
[0105] Prepare 75%-85% of the cleaning agent proposed in the present application to the production tank capacity and inject it into the production tank;
[0106] Heat and maintain the temperature inside the production tank at 60°C-70°C, stir and soak for at least 20 minutes, and then empty the production tank.
[0107] As a preferred embodiment, the cleaning agent proposed in the present application with a production tank capacity of 75%-85% can be prepared through the following steps.
[0108] First, according to the mass of the residual ointment matrix in the production line, a cleaning agent of a certain concentration is prepared using the cleaning composition of the present application, and the concentration of the cleaning agent does not exceed 0.5% (w / v);
[0109] Secondly, the mass of immersion cleaning agent required for the production tank capacity of 75%-85% is calculated based on the concentration of the immersion cleaning agent;
[0110] Then, a soaking cleaning agent is prepared according to the mass fraction of the cleaning agent components proposed in the present application and dissolved in water, heated to 60°C-70°C and injected into the production tank;
[0111] Finally, continue to inject water to 75%-85% of the production tank capacity.
[0112] The cleaning agent circulation cleaning steps include:
[0113] Prepare 15%-25% of the cleaning agent proposed in this application in a production tank capacity;
[0114] Heat the cleaning agent to 60℃-70℃;
[0115] Use a cleaning agent at 60℃-70℃ to circulate and flush the production tanks for 20-30 minutes, and circulate and flush the pipelines for 10-20 minutes.
[0116] As a preferred embodiment, the cleaning agent proposed in the present application with a production tank capacity of 15%-25% can be prepared through the following steps.
[0117] First, the concentration of the cleaning agent is determined based on the mass of the residual ointment matrix in the production line;
[0118] Then, the mass of flushing cleaning agent required for 15%-25% of the production tank capacity is calculated based on the concentration of the cleaning agent;
[0119] Finally, a flushing cleaning agent is prepared according to the mass fractions of the cleaning agent components proposed in the present application, and the prepared flushing cleaning agent is dissolved in 15%-25% of the water in the production tank capacity to form the flushing cleaning agent.
[0120] In addition, the cleaning method may further include a purified water pre-rinsing step before the cleaning agent circulating rinsing step, and / or a purified water rinsing step after the cleaning agent circulating rinsing step.
[0121] As a preferred embodiment, the purified water pre-rinsing step uses 60℃-70℃ purified water to circulate and flush the production tanks for 10-15 minutes and the pipelines for 5-10 minutes; the purified water flushing step uses room temperature purified water to circulate and flush the production tanks for 10-15 minutes and the pipelines for 5-10 minutes.
[0122] Experimental Example 5
[0123] Select two common cleaning methods: stirring immersion and spray cleaning for investigation and research. Figure 1 As shown. Add an appropriate amount of purified water to a 1000ml beaker and heat it to 60°C in a water bath. Weigh 5g of the cleaning composition according to Examples 2-3 and dissolve them in purified water. Add the remaining purified water until the total amount reaches 1000ml, then the concentration of the cleaning agent is 0.5% (w / v). Stir with a magnetic stirrer for 10min at a speed of 900R / min to mix the cleaning agent evenly. Use a 10×10cm 316 steel plate to simulate the inner wall of the tank, and evenly apply 15g of white vaseline (about 1.0mm thick) on both sides. The cleaning method uses a stirring, soaking and spraying cleaning method. The cleaning temperature is 60°C and the cleaning time is set to 20 minutes. Detect the residual amount of vaseline, and at the same time, visual cleaning, no water droplets hanging on the wall or water flow damage (no water breakage) are the acceptance conditions for cleaning. The results are shown in Table 4.
[0124] Table 4:
[0125] Cleaning method temperature Cleaning time Visual status Residue(g) Cleaning effectiveness Stir and soak 60℃ 20min Visual cleaning 1.06 92.93％ Spray cleaning 60℃ 10min Visual cleaning 0.54 96.40％
[0126] It can be seen from the above experimental results that the cleaning composition and detergent of the present application can achieve a cleaning effect of more than 90% by using two common cleaning methods: stirring and immersing and spraying.
[0127] Experimental Example 6
[0128] The following is a specific example of using the cleaning agent of the present application to clean the residue of the ointment matrix of a drug production line containing an ointment matrix to further illustrate the specific application and application effect of the cleaning agent of the present application. In this specific embodiment, the production line equipment of the drug production line includes a production tank and a pipeline, wherein the production tank is specifically a mixing tank.
[0129] A 50L mixing tank was used to produce 30kg of a certain ointment drug. In addition to white vaseline, the ointment matrix of the ointment drug also contained liquid paraffin, and the mass of liquid paraffin was about 1 / 10 of that of white vaseline. After the drug production was completed, the mass of the residual ointment matrix in the mixing tank was about 535g when tested online.
[0130] Detergent soaking cleaning steps:
[0131] Step 1: prepare 80% of the capacity of the mixing tank of the cleaning agent proposed in the present application and inject it into the mixing tank.
[0132] The total amount of immersion cleaning agent is 50×80%=40L;
[0133] The mass of the ointment matrix required to be cleaned for every 1000ml of soaking cleaning agent is 535 / 40=13.375g;
[0134] The concentration of the immersion cleaning agent was 0.43% (w / v);
[0135] The mass of the immersion cleaning agent is 40×1000×0.43%=172g;
[0136] When the soaking cleaning agent is 24 parts of Span 20, 2 parts of Span 40, 8 parts of Tween 60, 16 parts of Tween 80, 4 parts of AEO-3, 32 parts of AEO-5, 1 part of sodium dodecylbenzene sulfonate, and 1 part of potassium hydroxide, the amount of each component added is calculated according to the proportion; it can be determined that Span 20 is 172×27.3%=46.956g, Span 40 is 172×2.3%=3.956g, Tween 60 is 172×9.1%=15.6 52g, Tween 80 is 172×18.2%=31.304g, AEO-3 is 172×4.5%=7.74g, AEO-5 is 172×36.4%=62.608g, sodium dodecylbenzene sulfonate is 172×1.1%=1.892g, potassium hydroxide is 172×1.1%=1.892g; weigh each component according to the corresponding mass of each component, dissolve in appropriate amount of purified water, heat to 60°C, and inject into the mixing tank after the soaking cleaning agent is dissolved. Continue to add purified water to 80% (40L) of the mixing tank capacity.
[0137] Step 2: Maintain the temperature in the mixing tank at 60°C and adjust the speed of the stirring blade to 50% of the maximum speed for immersion for 30 minutes. After the immersion is completed, empty the mixing tank.
[0138] Purified water pre-rinsing steps:
[0139] Step 3: Use 60°C purified water to pre-flush the mixing tank for 15 minutes and pre-flush the pipeline for 10 minutes.
[0140] Cleaning agent circulation cleaning steps:
[0141] Step 4, prepare 20% of the cleaning agent proposed in the present application in the mixing tank.
[0142] The total amount of flushing cleaning agent is 50×20%=10L;
[0143] The mass of ointment matrix required to be cleaned for every 1000ml of flushing cleaning agent is 535 / 40=13.375g;
[0144] Prepare a flushing cleaning agent with a concentration of 0.43%;
[0145] The mass of the flushing cleaning agent is 10×1000×0.43%=43g;
[0146] When the rinse cleaning agent uses the cleaning composition of Example 2-3, that is, 24 parts of Span 20, 2 parts of Span 40, 8 parts of Tween 60, 16 parts of Tween 80, 4 parts of AEO-3, 32 parts of AEO-5, 1 part of sodium dodecylbenzene sulfonate, and 1 part of potassium hydroxide by weight, the amount of each component added is calculated according to the proportion; it can be determined that Span 20 is 43×27.3%=11.739g, Span 4 is 2 parts, Tween 60 is 8 parts, Tween 80 is 16 parts, AEO-3 is 4 parts, AEO-5 is 32 parts, sodium dodecylbenzene sulfonate is 1 part, and potassium hydroxide is 1 part. 0 is 43×2.3%=0.989g, Tween 60 is 43×9.1%=3.913g, Tween 80 is 43×18.2%=7.826g, AEO-3 is 43×4.5%=1.935g, AEO-5 is 43×36.4%=15.652g, sodium dodecylbenzene sulfonate is 43×1.1%=0.473g, potassium hydroxide is 43×1.1%=0.473g;
[0147] Weigh each component according to its corresponding mass, dissolve it in 10L of purified water to form a flushing cleaning agent.
[0148] Step 5, heat the rinse cleaning agent to 60°C.
[0149] Step 6, use a 60°C flushing cleaning agent to circulate and flush the mixing tank for 25 minutes and the pipeline for 15 minutes.
[0150] Purified water rinsing steps:
[0151] Step 7: Use room temperature purified water to flush the mixing tank for 10 minutes and flush the pipeline for 10 minutes.
[0152] During the purified water rinse step, clean wastewater is taken from the drain for TOC testing. During the test, the METTLER portable 450TOC analyzer is used. The analyzer is placed as close to the sampling point as possible, and the analyzer is ensured to be operated in a vertical or horizontal position. The inlet tube is connected to the inlet of the analyzer, and the drain pipe is connected to the outlet of the analyzer. The free end of the inlet tube is woven into the sampling point of the solution to be tested, and the drain pipe is placed in the collection tank or container, and then powered on. Slowly open the stop valve to allow the solution to begin to flow into the analyzer. When the solution begins to flow, the analyzer automatically controls the flow rate. Select the measurement button to read the result. The analyzer display can directly display the TOC test results. The TOC test results are shown in Table 5.
[0153] Table 5:
[0154] Time (min) 3 4 5 6 7 8 9 10 TOC(mg / L) 0.19 0.12 0.11 0.11 0.12 0.11 0.11 0.10
[0155] It can be seen that after 3 minutes, the total organic carbon content in the solution was less than 0.5 mg / L, which complies with the drug production quality and safety management regulations.
[0156] The cleaning agent proposed in the present application has a good cleaning effect on the ointment and greatly reduces the amount of cleaning agent used, which not only reduces the cost but also greatly reduces the risk of cleaning agent residue. By emulsifying the cleaning agent, the ointment is wrapped in droplets and will not precipitate even if the temperature drops to room temperature. This not only eliminates the risk of residual matter being brought into the next production, but also saves the trouble of manually collecting and filtering the ointment and replacing the filter.
[0157] In addition, the temperature of the cleaning agent during cleaning only needs to reach 60°C to obtain a good cleaning effect, which is much lower than the 80°C cleaning temperature required by the prior art. The existing commonly used cleaning method for ointment products is to use water above 80 degrees to melt the ointment matrix at high temperature and wash it away. However, in the drainage pipeline, when the temperature is low (especially in the Northeast), the ointment matrix precipitates and causes emission pollution, and TOC detection is non-compliant. Moreover, high water temperature also causes energy loss. The cleaning method proposed in this application overcomes the drawbacks of the prior art.
[0158] The above is only a specific implementation of the present application. Under the above teachings of the present application, those skilled in the art can make other improvements or modifications based on the above embodiments. Those skilled in the art should understand that the above specific description is only to better explain the purpose of the present application, and the protection scope of the present application shall be based on the protection scope of the claims.
[0159] In addition, those skilled in the art will appreciate that, although some embodiments described herein include certain features included in other embodiments but not other features, the combination of features of different embodiments is meant to be within the scope of the present application and form different embodiments. For example, in the claims below, any one of the claimed embodiments may be used in any combination.
Claims
1. A cleaning composition, characterized in that By mass, it includes the following components: Span 16.5-52; Tween 12-30 parts; 25-72 parts of fatty alcohol polyoxyethylene ether; The Span includes Span 20 and / or Span 40, the Tween includes Tween 60 and / or Tween 80, and the fatty alcohol polyoxyethylene ether includes AEO-3 and / or AEO-5.
2. A cleaning composition according to claim 1, characterized in that: Calculated by weight, 0-2 parts of sodium dodecylbenzene sulfonate are also included.
3. A cleaning composition according to claim 1, characterized in that: Calculated by weight, the invention also includes 0.5-2 parts of an alkaline regulator.
4. A cleaning composition according to claim 3, characterized in that: The alkaline regulator is selected from one or more of potassium hydroxide, sodium hydroxide or sodium bicarbonate.
5. A cleaning composition according to any one of claims 1 to 4, characterized in that: By mass, it includes the following components:
6. A cleaning agent, characterized in that: The cleaning composition comprises the cleaning composition according to any one of claims 1 to 5 and water.
7. A cleaning agent according to claim 6, characterized in that: The mass volume concentration of the cleaning agent is not higher than 0.5% (w / v).
8. Use of a cleaning agent according to claim 6 or 7 in cleaning drug residues, including cleaning of drug production line equipment, such as production tanks and / or pipelines. Optionally, the production tanks include mixing tanks and / or blending tanks.
9. The use according to claim 8, characterized in that: The medicine is a medicine containing an ointment base. Optionally, the medicine is an ointment preparation, a gel preparation or a suppository; optionally, the ointment base includes the oily base in the ointment preparation, the natural gum base in the gel preparation and / or the oily base in the suppository; preferably, the oily base in the ointment preparation includes one or more of vaseline, liquid paraffin, lanolin, ozokerite, beeswax, saturated and unsaturated fatty acid esters, vegetable oils, and dimethyl silicone oil; preferably, the natural gum base in the gel preparation is selected from one or more of pectin, alginic acid, and guar gum; preferably, the oily base in the suppository is selected from one or more of cocoa butter, semi-synthetic or fully synthetic fatty acid glycerides.
10. The use according to claim 8, characterized in that: The cleaning agent is used for cleaning at 60°C-70°C.