Non-ionic N-vinylbutyrolactam iodine with high stability and its manufacturing process

Abstract

A process for producing a nonionic N-vinyl butyrolactam iodine with high stability, characterized in that nonionic N-vinyl butyrolactam, iodine and abrasive aid are stirred at a temperature of 50°C to 90°C and a stirring speed of 150 to 800 rpm for 1 to 12 hours to produce the nonionic N-vinyl butyrolactam iodine with high stability, wherein the nonionic N-vinyl butyrolactam has a K-value of 32±1, a PD-value of the main peak of ≤ 1.6, and a water content of ≤ 2.5%, wherein the abrasive aid comprises sodium citrate.

Description

Technical field The present invention relates to the technical field of compounds, in particular the technical field of non-ionic N-vinyl butyrolactam iodine, especially a non-ionic N-vinyl butyrolactam iodine with high stability and its manufacturing process. State of the art Non-ionic N-vinylbutyrolactam-iodine (PVP-I), or PVP-I for short, is a yellowish-brown to reddish-brown amorphous powder. It is an amorphous iodine complex formed by the complexation of non-ionic N-vinylbutyrolactam (PVP) and iodine, and is a type of iodophor. PVP-I is an excellent disinfectant, initially included in the Chinese Pharmacopoeia in 1990. It has a long-lasting disinfectant effect and is a broad-spectrum disinfectant with strong antiseptic activity against viruses, bacteria, fungi, and fungal spores. Therefore, it is approved by the Chinese Pharmacopoeia as a disinfectant suitable for use on humans.Non-ionic N-vinyl butyrolactam (PVP-I) is a non-ionic surfactant that has no antiseptic effect itself. However, it can increase the solubility of iodine and improve the wettability and penetration of the iodine solution on the object, thereby increasing the affinity between available iodine and cell membranes and allowing the available iodine to be introduced directly onto the cell membranes or cytoplasm. This kills bacteria within seconds and enhances the bactericidal effect. At the same time, PVP-I is highly soluble in water, does not cause irritation, allergies, or poisoning of the skin or mucous membranes, and is well-regarded both domestically and internationally. Furthermore, PVP-I can be used not only as an aqueous solution but also as a solid in certain specific applications. This makes the PVP-I complex widely used for antiseptics and disinfection in various fields, thus expanding the range of applications for iodine.It can be widely used for disinfection in hospitals both at home and abroad. However, PVP-I produced using conventional methods does not exhibit good stability. Its available iodine content decreases during storage due to decomposition and sublimation, making it impossible to meet the quality requirements we promote. PVP-I is particularly unstable in summer. Therefore, it is disadvantageous for long-term storage and use. For this purpose, it is urgently needed to provide a highly stable, non-ionic N-vinyl butyrolactam iodine that is suitable for long-term storage and use. CN 101838359 A describes non-ionic N-vinyl butyrate lactam iodine, highly stable non-ionic N-vinyl butyrate lactam iodine and a corresponding process for its production. VIVAPHARM describes an N-vinyl butyrolactam with a K-value of 29-32, see www.pharmaexcipients.com / product / vivapharm-pvp-k30 . Description of the invention To eliminate the aforementioned problems and disadvantages, the main objective of the present invention is to offer a non-ionic N-vinylbutyrolactam-iodine with high stability and its manufacturing process, wherein the non-ionic N-vinylbutyrolactam-iodine has high stability, which is advantageous for long-term storage and application and is suitable for distribution and use. To solve the aforementioned problem, the present invention provides, on the one hand, a manufacturing process for nonionic N-vinyl butyrolactam iodine, wherein nonionic N-vinyl butyrolactam, iodine, and an abrasive aid are stirred at a temperature of 50°C to 90°C and a stirring speed of 150 to 800 rpm for 1 to 12 hours to produce the nonionic N-vinyl butyrolactam iodine with high stability, wherein the nonionic N-vinyl butyrolactam has a K-value of 32 ± 1, a PD-value of the main peak of ≤ 1.6, and a water content of ≤ 2.5%, wherein the abrasive aid comprises sodium citrate. The reaction time is calculated from the start of the reaction. A sample is taken every half hour and the available iodine content is determined. The reaction is stopped when the reaction has been carried out for approximately 4 hours and the available iodine content of the product reaches 11.0%. If a higher available iodine content is desired, the reaction time can be extended accordingly. The expert can add the appropriate amount of grinding aid based on their experience. Preferably, the amount of the abrasive aid is 0.02 to 2% of the total amount of nonionic N-vinyl butyrolactam and iodine. Preferably, the N-vinyl butyrolactam is 42 g, the iodine is 8 g, and the grinding aid is 0.01 to 1.0 g. The temperature can be provided in various suitable ways. Preferably, the temperature can be provided by means of an oil bath. Nonionic N-vinyl butyrolactam can be provided in various suitable ways. Preferably, it can be produced by a reaction in which N-vinyl butyrolactam (NVP), an initiator, and water react at a temperature of 55 to 80°C under an inert gas for 0.5 to 8 hours, followed by drying. For example, vacuum drying ovens can be used for drying. The initiator could be, for example, ABIN. The inert gas can be any suitable gas. Nitrogen is preferred. The nonionic N-vinyl butyrolactam can be any nonionic N-vinyl butyrolactam that has a Ka value of 32 ± 1, a main peak PD value of ≤ 1.6, and a water content of ≤ 2.5%. Preferably, the nonionic N-vinyl butyrolactam is PVP-K32. On the other hand, the present invention provides a non-ionic N-vinyl butyrolactam iodine with high stability, characterized in that it is produced by the manufacturing process described above. The advantages of the present invention are as follows: 1. According to the invention, to produce the highly stable nonionic N-vinyl butyrolactam, nonionic N-vinyl butyrolactam, iodine, and an abrasive aid are stirred for 1 to 12 hours at a temperature of 50°C to 90°C and a stirring speed of 150 to 800 rpm, wherein the nonionic N-vinyl butyrolactam has a K-value of 32 ± 1, a PD value of the main peak of ≤ 1.6, and a water content of ≤ 2.5%, wherein the abrasive aid comprises sodium citrate. The resulting nonionic N-vinyl butyrolactam with iodine thus possesses high stability, which is advantageous for long-term storage and application and is suitable for widespread distribution and use. 2. In the present invention, no general PVPK30 is used, but rather non-ionic N-vinyl butyrolactam with a K-value of 32±1, a PD value of the main peak of ≤ 1.6 and a water content of ≤ 2.5%, e.g.PVP-K32 from Shanghai Yuking Chemical Technology GmbH is used. Compared to general PVP-K30, PVP-K32 has a higher K-value, a lower PD-value for characterizing the molecular weight distribution, and a lower water content. The combined effect of these three factors ensures the complete execution of the reaction. The reasons for this are as follows: PVP molecular chains with a higher K-value are relatively longer and have more active sites, and a narrower molecular weight distribution means a more uniform distribution of the polymer and a more regular distribution of the active sites along the molecular chain. Simultaneously, the lower water content can increase the mobility of the PVP and thus the likelihood of reaction with iodine within the same timeframe. The synergistic effect of these three factors can fully ensure complex formation between PVP and iodine and improve the stability of the PVP-iodine solution. Examples of implementation To better understand the present invention, it will be explained in more detail using the following exemplary embodiments. The relevant starting materials and apparatus are described below: Starting materials: PVP-K32 (CP, K-value of 32±1, PD-value of the main peak of ≤ 1.6, water content of ≤ 2.5%, Shanghai Yuking Chemical Technology GmbH), iodine (99.5%, CP, Turkmenistan), starch indicator (homemade), sodium thiosulfate standard solution (homemade), sodium citrate (reagent grade). Apparatus: <row> <cell>High-speed grinder< / cell> <cell> DFT-100< / cell> <cell> Shanghai Dingguang Machine Ltd< / cell> < / row> <row> <cell> Thermostatic circulating air drying oven< / cell> <cell> DZF-6021< / cell> <cell> Shanghai Suopu Instrument GmbH< / cell> < / row> <row> <cell> Constant speed mixer< / cell> <cell> S312< / cell> <cell> Shanghai Meiyingpu Instrument GmbH< / cell> < / row> <row> <cell> Electronic analytical balance< / cell> <cell> FA2004< / cell> <cell> Shanghai Liangping Instrument GmbH< / cell> < / row> <row> <cell> Thermostatic water bath kettle< / cell> <cell> RE-205< / cell> <cell> Gongyi Yingyuyuhua Instrument Factory< / cell> < / row> <row> <cell> Base burette< / cell> <cell> 50ml< / cell> <cell> Shanghai Heqi Glassware GmbH< / cell> < / row> <p xml:id="_9b4c5d0062" n="0021">The corresponding determination methods are presented as follows: <list xml:id="_9b4c5d0063" type="bulleted"> <item>Determination of Available Iodine: The concentration of the sample is determined according to the method of the Chinese Pharmacopoeia. The determination of available iodine is carried out according to USP: 1 g of sample is weighed accurately and placed in a beaker, and water is added while stirring. After the sample is completely dissolved, the solution is transferred to a 100 mL volumetric flask. Two 20 mL samples of solution are accurately pipetted and added to the iodine titration flasks. The solutions are titrated with sodium thiosulfate standard solution (0.1 mol / L). When the color turns almost yellow, starch indicator is added, and the solution is titrated further with sodium thiosulfate standard solution until the blue color disappears. The volume of sodium thiosulfate solution consumed is recorded, and the available iodine content of the samples is calculated.< / item> < / list> <p xml:id="_9b4c5d0065" n="0022">Stability determination: According to the acceleration test, a specific amount of the sample is weighed to prepare the 1% solution. The corresponding amount of the solution is transferred to the iodine concentration flask and stored for 15 hours at 85°C. The available iodine content is then determined. The loss of available iodine is calculated. Example 1 (comparative example) <p xml:id="_9b4c5d0067" n="0023"> 8.0 g of crushed iodine powder and 42.0 g of PVP-K30 were weighed precisely and placed in a 250 ml three-necked flask. The mixture was reacted in an oil bath at 80°C for approximately 4 hours with stirring at a speed of 150 rpm. Example 2 (comparative example) <p xml:id="_9b4c5d0069" n="0024"> 8.0 g of crushed iodine powder and 42.0 g of PVP-K32 were weighed precisely and placed in a 250 ml three-necked flask. The mixture was reacted in an oil bath at 80°C for approximately 4 hours with stirring at a speed of 150 rpm. Example 3 <p xml:id="_9b4c5d0071" n="0025">8.0 g of crushed iodine powder, 42.0 g of PVP-K30, and 0.5 g of sodium citrate were weighed precisely and placed in a 250 ml three-necked flask. The mixture was reacted in an oil bath at 80°C for approximately 4 hours with stirring at a speed of 800 rpm. Example 4 <p xml:id="_9b4c5d0073" n="0026"> 8.0 g of crushed iodine powder, 42.0 g of PVP-K32, and 0.5 g of sodium citrate were weighed precisely and placed in a 250 ml three-necked flask. The mixture was reacted in an oil bath at 80°C for approximately 4 hours with stirring at a speed of 800 rpm. Example 5 <p xml:id="_9b4c5d0075" n="0027"> 8.0 g of crushed iodine powder, 42.0 g of PVP-K32, 0.01 g of sodium citrate, and 0.5 g of sodium carbonate were precisely weighed and placed in a 250 ml three-necked flask. The mixture was reacted in an oil bath at 50°C for approximately 1 hour with stirring at a speed of 400 rpm. Example 6 <p xml:id="_9b4c5d0077" n="0028"> 8.0 g of crushed iodine powder, 42.0 g of PVP-K32, and 1.0 g of sodium citrate were weighed precisely and placed in a 250 ml three-necked flask. The mixture was reacted in an oil bath at 90°C for approximately 12 hours with stirring at a speed of 800 rpm. <p xml:id="_9b4c5d0078" n="0029">The results regarding available iodine and stability of the PVP-I solutions produced in Examples 1 to 6 are presented below: Table 1 shows the stability of the available iodine content of the 1% PVP-I solution stored for 15 hours at 85°C. <title desc="title">Table 1 shows the stability of the available iodine content of a 1% PVP-I solution stored for 15 hours at 85°C.< / title> Example 1 *11,158,59-22,96 Example 2 *11.2110.03-10.52 Example 311,2710,65-5,47 Example 411,3210,96-3,11 Example 511,1910,82-3,22 Example 611,2210,86-3,17 Note: The available iodine content is calculated based on dried products. * = Comparative example The stability results from the table show that the PVP-I sample prepared with the abrasive sodium citrate exhibits significantly higher stability than the standard PVPI sample prepared without sodium citrate. This is because the added sodium citrate enhances the internal excitation between iodine and PVP-K32, resulting in complete complex formation and thus higher stability for the PVPI. However, the highly active PVPK32 from Shanghai Yuking GmbH, compared to PVPK30 from other companies, has a higher Kw value, a lower PD value for characterizing the molecular mass distribution, and a lower water content. The combined effect of these three factors ensures that the reaction can be completed.The reasons for this are that the PVP molecular chains with higher K-values ​​are relatively longer and have more active sites, while a narrower molecular mass distribution results in a more uniform distribution of the polymer and a more regular distribution of the active sites along the molecular chains. Simultaneously, lower water content can improve the mobility of PVPK32 and increases its potential for reaction with iodine within the same timeframe. Through the synergistic effect of these three factors, complex formation between PVP and iodine can be complete, thus improving stability. The starting material PVP with a molecular mass of K32, a PD value of less than 1.6, and a water content of less than 2.5 is used. This is an important factor for the production of stable PVPI. The abrasive aid comprises sodium citrate. With this process according to the invention, the available iodine content can reach more than 11%. Stability is significantly improved, and the shelf life can exceed three years. It can meet market requirements. Furthermore, the storage time of the solution produced with the PVPI sample can be significantly extended, which is advantageous for the long-term storage of PVP-I disinfectants. In summary, the non-ionic N-vinylbutyrolactam-iodine according to the invention has high stability, making long-term storage and use advantageous and suitable for widespread distribution and use. The present invention is described using specific examples. However, it is obvious that various modifications and substitutions can be made without deviating from the scope of protection of the present invention. Therefore, the description should be regarded not as a limitation but as an explanation.

Claims

A process for the production of a nonionic N-vinyl butyrolactam iodine with high stability, characterized in that nonionic N-vinyl butyrolactam, iodine and abrasive aid are stirred at a temperature of 50°C to 90°C and a stirring speed of 150 to 800 rpm for 1 to 12 hours to produce the nonionic N-vinyl butyrolactam iodine with high stability, wherein the nonionic N-vinyl butyrolactam has a K-value of 32±1, a PD-value of the main peak of ≤ 1.6, and a water content of ≤ 2.5%, wherein the abrasive aid comprises sodium citrate. Method for producing the nonionic N-vinyl butyrolactam iodine with high stability according to claim 1, characterized in that the amount of abrasive added is 0.02 to 2% of the total amount of nonionic N-vinyl butyrolactam and iodine. Method for producing the nonionic N-vinylbutyrolactam iodine with high stability according to claim 2, characterized in that the nonionic N-vinylbutyrolactam is 42 g, the iodine is 8 g and the abrasive aid is 0.01 to 1.0 g. Method for producing the nonionic N-vinylbutyrolactam iodine with high stability according to claim 1, characterized in that the temperature is provided by means of an oil bath. A process for the production of the nonionic N-vinylbutyrolactam iodine with high stability according to claim 1, characterized in that the nonionic N-vinylbutyrolactam is produced by a reaction in which N-vinylbutyrolactam, initiator and water react at a temperature of 55 to 80°C under inert gas for 0.5 to 8 hours, and the subsequent drying is carried out. Method for producing the nonionic N-vinylbutyrolactam iodine with high stability according to claim 5, characterized in that the inert gas is nitrogen. Method for producing the nonionic N-vinyl butyrolactam iodine with high stability according to claim 1, characterized in that the nonionic N-vinyl butyrolactam is PVP-K32. Non-ionic N-vinylbutyrolactam iodine with high stability, characterized in that it is produced by the process for producing the non-ionic N-vinylbutyrolactam iodine with high stability according to one of claims 1 to 7.