A kind of preparation method of chlorhexidine organic acid salt

Abstract

The invention belongs to the technical field of chemical raw material drug preparation, and discloses a method for preparing chlorhexidine organic acid salt, in particular chlorhexidine acetate and gluconate, comprising the steps of: first, weighing 330 to 400 parts of chlorhexidine base according to a batch amount, putting them into a reactor pre-filled with purified water, and stirring and slurrying them completely; then, adding 92 to 270 parts of organic acidulant, adjusting pH=6.0 to 9.0, turning on steam, heating to 75°C to 85°C, and neutralizing for 1.0h to 2.0h; after the reaction is completed, adding 6.0g / L to 10.0g / L composite adsorbent, adsorbing and purifying at 75°C to 85°C for 0.5h to 1.0h; after the adsorption and purification is completed, filtering while hot, cooling the filtrate, and obtaining chlorhexidine organic acid salt. The method is simple and flexible, the finished product has pure color, low chlorhexidine impurities, high purity, no wastewater generation, and high product yield.

Description

Technical Field

[0001] The invention relates to a preparation method of chlorhexidine organic acid salt, in particular to a preparation method of chlorhexidine acetate and gluconate, and belongs to the technical field of chemical raw material drug preparation. Background Art

[0002] Chlorhexidine (CHX), chemical formula: 22 H 30 N 10 C l2, chemical name is chlorhexidine, commonly known as chlorhexidine, chemical structure is as follows:

[0003]

[0004] CHX is an odorless, white or off-white, crystalline powder with a melting point of 132°C to 136°C. It is soluble in ethanol and only slightly soluble in water.

[0005] Since the structure of CHX contains multiple imino groups (=NH), it is alkaline as a whole and difficult to dissolve in water. However, CHX can easily undergo acid-base neutralization reaction with acid to obtain the corresponding salt that exists stably. People generally react it with hydrochloric acid, acetic acid, and gluconic acid to make the corresponding salt for use.

[0006] my country introduced chlorhexidine into the healthcare field in 1954. Due to its good antibacterial properties and good safety, it has been widely used in many healthcare products, including oral mouthwash, oral patches, eye drops, medical procedure lubricating gel, powder, dressing, scrub and central venous catheter. In addition, it is increasingly used as a preservative in cosmetics and daily necessities.

[0007] However, it should be noted that chlorhexidine may cause allergic reactions. A recent survey from 13 centers reported 252 cases of chlorhexidine allergy and listed it as the top four most common causes of perioperative allergy, along with neuromuscular blockers, antibiotics, and latex.

[0008] Chinese patent CN1181845921A discloses a method for preparing chlorhexidine impurity J gluconate, wherein the chlorhexidine impurity J gluconate is the glucose salt of impurity J in the European Pharmacopoeia. The prepared chlorhexidine impurity J gluconate is used as a reference substance for qualitative and quantitative research of impurity J in chlorhexidine quality research, and the content of chlorhexidine impurity J is controlled to ensure the quality of the raw material drug.

[0009] During the production process of chlorhexidine gluconate solution, various chlorhexidine impurities are generated, among which chlorhexidine impurity J is an impurity in the European Pharmacopoeia. The European Pharmacopoeia (EP) and the United States Pharmacopoeia (USP) also stipulate that the content of chlorhexidine impurity J in the acceptance criteria of chlorhexidine shall not exceed 0.4%. Closely related to the quality of drugs is the control of impurities contained in drugs, and the control of impurities is particularly important. As for whether there is a causal relationship between impurities and chlorhexidine allergic reactions, it is currently impossible to give a clear conclusion.

[0010] Chinese patent CN11302976 A discloses a method for preparing chlorhexidine base, wherein n-butanol, hexamethylenediamine and hydrochloric acid are first mixed, and then triethylamine and sodium dicyanamide are added to carry out a condensation reaction, and the first condensation reaction is terminated, and then p-chloroaniline, water and hydrochloric acid are added to carry out a secondary condensation reaction, and the secondary condensation reaction is terminated, and then liquid alkali is added for alkalization, crystallization, and rejection filtration are performed to obtain a crude chlorhexidine base; the crude product is washed, rejected and filtered, and dried to obtain chlorhexidine base. The present invention adopts the principle of one-pot cooking to prepare chlorhexidine base, reduces the reaction steps and the amount of wastewater, simplifies the operation, and significantly improves the quality and yield. However, the yield of chlorhexidine base is only 60.0% to 68.0%, and the content is 99.17% to 99.78%, and it still contains a relatively high amount of trace impurities. Summary of the invention

[0011] In view of the deficiencies in the prior art, the object of the present invention is to provide a method for preparing chlorhexidine organic acid salt with guaranteed product purity, high yield and simple process.

[0012] To achieve the above object, the present invention provides a method for preparing chlorhexidine organic acid salt, comprising the steps of:

[0013] First, 330 to 400 parts of chlorhexidine base are weighed according to a batch amount, put into a reaction kettle pre-filled with purified water, and stirred to completely slurry. Chlorhexidine base has low solubility in water, and sufficient stirring and slurry dispersion can prevent agglomeration, facilitate the smooth progress of subsequent neutralization reaction, reduce reactant encapsulation and embedding, and improve reaction efficiency and finished product yield.

[0014] Then, add 92 to 270 parts of organic acid acidifier, adjust the pH to 6.0 to 9.0, turn on the steam, heat to 75°C to 85°C, and neutralize for 1.0h to 2.0h. Chlorhexidine is not very soluble in water. In order to better exert its antibacterial effect, chlorhexidine is usually made into salt form. Chlorhexidine in the form of salt has enhanced solubility and stability, which is more conducive to storage and use. Commonly used chlorhexidine salts include hydrochloride, citrate, acetate, gluconate, etc. The solubility of organic acid salts is greater than that of inorganic acid salts. Organic acidifiers can use corresponding organic acids or organic acid anhydrides. Strictly controlling the ratio of reactants, the pH value at the reaction end, and the reaction temperature is the key to ensuring the efficiency of the neutralization reaction. The pH value at the reaction end can only be achieved when the ratio of reactants is reasonable. Generally, the reaction end shows the degree of the neutralization reaction. A pH value that is acidic may be due to excessive acidifier or incomplete reaction, and a pH value that is alkaline may be due to insufficient acidifier or incomplete reaction. Since the solubility of chlorhexidine salts increases with increasing temperature, maintaining an appropriate reaction temperature is a prerequisite for ensuring complete reaction. For different chlorhexidine salts, a clear material ratio, endpoint pH value and reaction temperature are formulated to improve reaction efficiency and product yield and reduce the generation of side reaction impurities.

[0015] After the neutralization reaction is completed, add 6.0g / L~10.0g / L composite adsorbent and adsorb and purify at 75℃~85℃ for 0.5h~1.0h. Some people are allergic to chlorhexidine products during use, and it is not ruled out that the impurities introduced during the synthesis of chlorhexidine products are the cause. Obviously, the content of these impurities cannot be very high. The adsorption purification method is simple, safe and low in cost. The key to adsorption purification lies in the selection of adsorbents. Organic adsorbents may reintroduce new organic matter, and inorganic adsorbents have limited adsorption capacity for organic impurities. The selection of composite adsorbents takes into account the removal of low-polarity and high-polarity impurities, giving full play to the characteristics and advantages of organic and inorganic adsorbents, thereby obtaining chlorhexidine salts with low impurities, high purity and pure color.

[0016] After the adsorption purification is completed, the product is filtered while hot and the filtrate is cooled to obtain chlorhexidine organic acid salt.

[0017] For the preparation of chlorhexidine acetate, the organic acidulant in step B is glacial acetic acid, and the mass ratio of chlorhexidine base to glacial acetic acid in step A is 400:92.

[0018] After the filtrate is cooled in step D, the process further comprises the steps of crystallization, centrifugal separation, washing, drying, crushing, screening, packaging and labeling to obtain a chlorhexidine acetate product and a crystallization mother liquor.

[0019] In order to improve the product yield, the above-mentioned crystallization mother liquor is further concentrated by distillation, cooled, and then subjected to secondary crystallization, centrifugal separation, washing, drying, crushing, screening, packaging and labeling steps to obtain the chlorhexidine acetate product and the secondary crystallization mother liquor, and the secondary crystallization mother liquor replaces or partially replaces the purified water in step A.

[0020] Obviously, the above scheme takes chlorhexidine acetate as an example to prepare solid crystals of chlorhexidine salt, and other solid crystals such as chlorhexidine hydrochloride and chlorhexidine citrate can also be prepared.

[0021] For the preparation of chlorhexidine gluconate, the organic acidulant in step B is gluconate delta lactone, and the mass ratio of chlorhexidine base to gluconate delta lactone in step A is 330:270.

[0022] After the filtrate is cooled in step D, the process further includes conditioning, packaging and labeling steps to obtain a finished chlorhexidine gluconate solution.

[0023] To ensure product quality, the conditioning of the filtrate after cooling in step D includes regulating the chlorhexidine gluconate content in the chlorhexidine gluconate solution between 19 g / mL and 21 g / mL and the pH value between 5.5 and 7.0.

[0024] The above scheme takes the preparation of chlorhexidine gluconate as an example to prepare a solution product of chlorhexidine gluconate, and other liquid products such as chlorhexidine hydrochloride and chlorhexidine citrate can also be prepared.

[0025] In summary, the present invention adopts two sets of schemes to couple, the process is simple and flexible, and can be adjusted in time according to needs to prepare various chlorhexidine salt products with low impurities, high purity and high yield.

[0026] To ensure the quality of chlorhexidine organic acid salt, the composite adsorbent used in step C is composed of the following by mass percentage:

[0027] Activated carbon 75%~85%

[0028] White clay 15%~25%

[0029] Further preferably, the composite adsorbent in step C has a composition by mass percentage of:

[0030] Activated carbon 80%

[0031] White clay 20%

[0032] This is also the crystallization of a large number of experimental results and practical experience.

[0033] On the other hand, in step A, chlorhexidine base is obtained by two-step condensation, alkalization and crystallization of biguanide and chlorhexidine hydrochloride. The basic starting point is that the process flow of the scheme is short, the product yield is high, the product quality is guaranteed, the impurities are low, and the purity is high.

[0034] Compared with the prior art, the present invention has the following beneficial effects:

[0035] 1. The present invention adopts a composite adsorbent to adsorb and purify a chlorhexidine organic acid salt solution, which can take into account the removal of high-polarity and low-polarity chlorhexidine impurities, ensure the purity of the product, and avoid the risk of allergies in some people suspected of chlorhexidine products.

[0036] 2. The present invention adopts a two-step condensation, alkalization and crystallization scheme of biguanide and chlorhexidine hydrochloride to obtain chlorhexidine base. Based on the short process flow of the chlorhexidine base, high product yield and guaranteed product quality, low impurities and high purity, the high yield and high purity of chlorhexidine organic acid salt are guaranteed.

[0037] 3. The present invention adopts two sets of schemes to couple, the process is simple and flexible, and can be adjusted in time according to needs to prepare various chlorhexidine salt products with low impurities, high purity and high yield. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 The invention discloses a process flow chart of a preparation method of chlorhexidine organic acid salt, in particular, a process flow chart of a preparation method of chlorhexidine acetate and gluconate. DETAILED DESCRIPTION

[0039] In order to make the purpose, technical scheme and advantages of the present invention clearer, the present invention is further described in detail below in conjunction with specific embodiments and with reference to the accompanying drawings. It should be understood that these descriptions are only exemplary and are not intended to limit the scope of the present invention. In addition, in the following description, the description of known knowledge and technology is omitted to avoid unnecessary confusion of the concept of the present invention.

[0040] [Example 1] Preparation of chlorhexidine acetate

[0041] 400 kg of chlorhexidine base is weighed and put into a 1500 L reactor pre-filled with 500 kg of purified water, and stirred to be completely slurried; 92 kg of glacial acetic acid is injected, the pH is adjusted to 8.5-9.0, steam is turned on, the temperature is raised to 80-85° C., and a neutralization reaction is carried out for 1.0-2.0 hours; after the reaction is completed, a composite adsorbent mixed with 3.75 kg of activated carbon and 1.25 kg of white clay is added, equivalent to 10.0 g / L, and adsorbed and purified at 80-85° C. for 0.5-1.0 hours; after the adsorption and purification is completed, the mixture is filtered while hot, the filtrate is cooled to 40-50° C., crystallized, centrifuged, washed with 300 kg of water, dried, crushed, sieved, packaged and labeled to obtain 400.0 kg of chlorhexidine acetate finished product and 791 kg of crystallization mother liquor.

[0042] The crystallization mother liquor was concentrated by distillation, cooled, subjected to secondary crystallization, centrifugal separation, washing, drying, crushing, sieving, packaging and labeling to obtain 15.0 kg of chlorhexidine acetate product and 776 kg of secondary crystallization mother liquor.

[0043] The cumulative output of chlorhexidine acetate is 415.0 kg, the theoretical output is 492.0 kg, the yield is 83.35%, and the purity of chlorhexidine acetate is 99.55% as determined by ultraviolet spectrophotometry.

[0044] [Example 2] Preparation of chlorhexidine acetate

[0045] 400 kg of chlorhexidine base was weighed and put into a 1500 L reactor pre-set with 500 kg of the secondary crystallization mother liquor of Example 1, and stirred to completely slurry; 92 kg of glacial acetic acid was injected, the pH was adjusted to 8.5-9.0, steam was turned on, the temperature was raised to 80° C.-85° C., and the neutralization reaction was carried out for 1.0 h-2.0 h; after the reaction was completed, a composite adsorbent mixed with 4.25 kg of activated carbon and 0.75 kg of white clay was added, equivalent to 10.0 g / L, and adsorbed and purified at 80° C.-85° C. for 0.5 h-1.0 h; after the adsorption and purification was completed, the mixture was filtered while hot, the filtrate was cooled to 40° C.-50° C., crystallized, centrifuged, the remaining 276 kg of the secondary crystallization mother liquor of Example 1 and 24 kg of water were washed, dried, crushed, sieved, packaged and labeled, and 405.0 kg of chlorhexidine acetate finished product and 785 kg of crystallization mother liquor were obtained.

[0046] The crystallization mother liquor was concentrated by distillation, cooled, subjected to secondary crystallization, centrifugal separation, washing, drying, crushing, sieving, packaging and labeling to obtain 14.8 kg of chlorhexidine acetate finished product and 770 kg of secondary crystallization mother liquor.

[0047] The cumulative output of chlorhexidine acetate is 419.8 kg, the theoretical output is 492.0 kg, the yield is 85.32%, and the purity of chlorhexidine acetate is 99.86% as determined by ultraviolet spectrophotometry.

[0048] [Example 3] Preparation of chlorhexidine acetate

[0049] 400 kg of chlorhexidine base was weighed and put into a 1500 L reactor pre-set with 500 kg of the secondary crystallization mother liquor of Example 2, and stirred to completely slurry; 92 kg of glacial acetic acid was injected, the pH was adjusted to 8.5-9.0, steam was turned on, the temperature was raised to 80-85 ° C, and the neutralization reaction was carried out for 1.0-2.0 hours; after the reaction was completed, a composite adsorbent mixed with 4.0 kg of activated carbon and 1.0 kg of white clay was added, equivalent to 10.0 g / L, and adsorbed and purified at 80-85 ° C for 0.5-1.0 hours; after the adsorption and purification was completed, the mixture was filtered while hot, the filtrate was cooled to 40-50 ° C, crystallized, centrifuged, the remaining 270 kg of the secondary crystallization mother liquor of Example 1 and 30 kg of water were washed, dried, crushed, sieved, packaged and labeled, and 408.0 kg of chlorhexidine acetate finished product and 795 kg of crystallization mother liquor were obtained.

[0050] The crystallization mother liquor was concentrated by distillation, cooled, subjected to secondary crystallization, centrifugal separation, washing, drying, crushing, sieving, packaging and labeling to obtain 14.5 kg of chlorhexidine acetate finished product and 778 kg of secondary crystallization mother liquor.

[0051] The cumulative output of chlorhexidine acetate is 422.5 kg, the theoretical output is 492.0 kg, the yield is 85.87%, and the purity of chlorhexidine acetate is 99.83% as determined by ultraviolet spectrophotometry.

[0052] [Example 4] Preparation of chlorhexidine gluconate

[0053] 330.0 kg of chlorhexidine base was weighed and put into a 3000 L reactor pre-filled with 2456 kg of purified water, and stirred to be completely slurried; 270.0 kg of glucono delta lactone was added, the pH was adjusted to 6.0-7.0, steam was turned on, the temperature was raised to 75-80° C., and a neutralization reaction was carried out for 1.0-2.0 hours; after the reaction was completed, 12.0 kg of a composite adsorbent of activated carbon and 3.0 kg of white clay was added, equivalent to 6.0 g / L, and adsorption and purification were carried out at 75-80° C. for 0.5-1.0 hours; after the adsorption and purification was completed, the mixture was filtered while hot, and the temperature was lowered by 35-40° C. to obtain 3000.0 kg of chlorhexidine gluconate solution with a specific gravity of 1.06, equivalent to 2830.0 L; the chlorhexidine gluconate content in the chlorhexidine gluconate solution was regulated and confirmed to be 20.5 g / mL and the pH was 6.5, which met the product requirements, and the mixture was packaged and labeled to obtain a finished chlorhexidine organic acid salt solution. The net mass of chlorhexidine gluconate is 580.15 kg, the theoretical output is 600.0 kg, the yield is 96.69%, and the chlorhexidine impurity J gluconate is detected by high performance liquid chromatography, and the result is = 0.16%, which meets the requirements.

[0054] [Comparative Example 1] Preparation of chlorhexidine gluconate

[0055] Weigh 330.0kg of chlorhexidine base, put it into a 3000L reactor pre-filled with 2456kg of purified water, stir and slurry completely; add 270.0kg of glucono delta lactone, adjust pH=6.0-7.0, turn on steam, heat to 75℃-80℃, neutralize for 1.0h-2.0h; cool by 35℃-40℃, obtain 3000.0kg of chlorhexidine gluconate solution, specific gravity 1.06, equivalent to 2830.0L, regulate and confirm that the content of chlorhexidine gluconate in the chlorhexidine gluconate solution is 20.8g / mL, pH=6.3, meet product requirements, package and label, and obtain the finished chlorhexidine organic acid salt solution. The net mass of chlorhexidine gluconate is 588.64kg, the theoretical output is 600.0kg, the yield is 98.10%, and the chlorhexidine impurity J gluconate is detected by high performance liquid chromatography, and the result is =0.56%, which does not meet the requirements.

[0056] [Comparative Example 2] Preparation of chlorhexidine gluconate

[0057] 330.0 kg of chlorhexidine base was weighed and put into a 3000 L reactor pre-filled with 2456 kg of purified water, and stirred to be completely slurried; 270.0 kg of glucono delta lactone was added, the pH was adjusted to 6.0-7.0, steam was turned on, the temperature was raised to 75-80° C., and the neutralization reaction was carried out for 1.0-2.0 hours; after the reaction was completed, 15.0 kg of activated carbon was added, equivalent to 6.0 g / L, and adsorption purification was carried out at 75-80° C. for 0.5-1.0 hours; after the adsorption purification was completed, the mixture was filtered while hot, and the temperature was lowered by 35-40° C. to obtain 3000.0 kg of chlorhexidine gluconate solution with a specific gravity of 1.06, equivalent to 2830.0 L; the chlorhexidine gluconate content in the chlorhexidine gluconate solution was regulated and confirmed to be 19.8 g / mL and the pH was 6.3, which met the product requirements, and the mixture was packaged and labeled to obtain a finished chlorhexidine organic acid salt solution. The net mass of chlorhexidine gluconate is 560.34 kg, the theoretical output is 600.0 kg, the yield is 93.39%, and the chlorhexidine impurity J gluconate is detected by high performance liquid chromatography, and the result is = 0.35%, which meets the requirements.

[0058] [Comparative Example 3] Preparation of chlorhexidine gluconate

[0059] 330.0 kg of chlorhexidine base was weighed and put into a 3000 L reactor pre-filled with 2456 kg of purified water, and stirred to be completely slurried; 270.0 kg of glucono delta lactone was added, the pH was adjusted to 6.0-7.0, steam was turned on, the temperature was raised to 75-80° C., and neutralization reaction was carried out for 1.0-2.0 hours; after the reaction was completed, 7.5 kg of activated carbon and 7.5 kg of kaolin composite adsorbent were added, equivalent to 6.0 g / L, and adsorption and purification were carried out at 75-80° C. for 0.5-1.0 hours; after the adsorption and purification was completed, hot filtration was performed, and the temperature was lowered by 35-40° C. to obtain 3000.0 kg of chlorhexidine gluconate solution with a specific gravity of 1.06, equivalent to 2830.0 L; the chlorhexidine gluconate content in the chlorhexidine gluconate solution was regulated and confirmed to be 20.1 g / mL and the pH was 6.3, which met the product requirements, and the product was packaged and labeled to obtain a chlorhexidine organic acid salt solution product. The net mass of chlorhexidine gluconate is 568.83 kg, the theoretical output is 600.0 kg, the yield is 94.80%, and the chlorhexidine impurity J gluconate is detected by high performance liquid chromatography, and the result is = 0.25%, which meets the requirements.

[0060] [Comparative Example 4] Preparation of chlorhexidine base

[0061] First, biguanidine is prepared.

[0062] Weigh 186.0kg hexamethylenediamine, 1200kg n-butanol and 100Kg water, add to a 3000L reactor, stir evenly, slowly drop about 260.0kg hydrochloric acid until pH=6-7, and react to generate hexamethylenediamine hydrochloride. Add 278.0kg sodium dicyandiamide, adjust pH=9.0-9.2 with about 1.0kg triethylamine, turn on steam heating to 110°C, perform addition reaction, start reflux for 3h, after reflux, heat the reaction product to distill, distill n-butanol under normal pressure, add water when n-butanol is about to evaporate to dryness, continue distillation until n-butanol is evaporated to dryness, add water again, accumulate 1280kg, precipitate solid product, suspend at 80°C for 1h, cool to 50°C, centrifuge to obtain 500.0kg filter cake, i.e. biguanide hexane.

[0063] Then, chlorhexidine hydrochloride was prepared.

[0064] 2000 kg of propylene glycol methyl ether was added to a 3000 L reactor (enamel), and then 325.0 kg of hydrochloric acid was added. 410.0 kg of p-chloroaniline was put into the reactor, heated to 45-50 ° C, pH was controlled to be 3-4, 500.0 kg of the above-obtained biguanidine was added for addition reaction, the temperature was raised to 115 ° C, refluxed, the reaction time was 6 hours, cooled to room temperature, and centrifuged to obtain 1299.5 kg of filter cake, i.e., chlorhexidine hydrochloride.

[0065] Finally, prepare the chlorhexidine base.

[0066] Add 1625 kg of 75% methanol to a 3000 L reactor, then add 450.0 kg of the above-obtained chlorhexidine hydrochloride, stir evenly, adjust pH to 12-13 with about 90.0 kg of sodium hydroxide, heat to 80° C., and reflux methanol. Reflux for 3 hours, cool to room temperature, centrifuge, wash with 400 kg of water for several times, and obtain 583.07 kg of filter cake, i.e., chlorhexidine base. The purity of chlorhexidine base reaches 99.83% by ultraviolet spectrophotometry.

[0067] Theoretically, 1.0 mol hexamethylenediamine, 2.0 mol sodium dicyanamide and 2.0 mol p-chloroaniline are consumed to obtain 1.0 mol chlorhexidine base. Calculated based on hexamethylenediamine, 116 kg hexamethylenediamine should produce 505.4 kg chlorhexidine base. In this example, 186.0 kg hexamethylenediamine can theoretically produce 810.38 kg (part of the chlorhexidine hydrochloride filter cake is used, calculated in equal proportion) chlorhexidine base, and the actual output is 1683.8 kg filter cake, which is equivalent to 757.71 kg on a dry basis with a moisture content of 55.0%, and a yield of 93.50%.

[0068] It should be understood that the above specific embodiments of the present invention are only used to illustrate or explain the principles of the present invention, and do not constitute a limitation of the present invention. Therefore, any modifications, equivalent substitutions, improvements, etc. made without departing from the spirit and scope of the present invention should be included in the protection scope of the present invention. In addition, the appended claims of the present invention are intended to cover all changes and modifications that fall within the scope and boundaries of the appended claims, or the equivalent forms of such scope and boundaries.

Claims

1. A method for preparing a chlorhexidine organic acid salt, characterized in that, The following steps are included: A) weighing 330 to 400 parts of chlorhexidine base in a batch, putting them into a reaction kettle pre-filled with purified water, and stirring to make the slurry complete; B) Add 92 to 270 parts of organic acidulant, adjust pH to 6.0 to 9.0, turn on steam, raise the temperature to 75°C to 85°C, and neutralize for 1.0h to 2.0h; C) After the reaction is completed, add 6.0g / L to 10.0g / L composite adsorbent and perform adsorption purification at 75℃ to 85℃ for 0.5h to 1.0h; D) adsorption purification is completed, filtered while hot, and the filtrate is cooled to obtain chlorhexidine organic acid salt; The organic acidulant in step B is glucono delta lactone, and the mass ratio of chlorhexidine base to glucono delta lactone in step A is 330:270; The composite adsorbent in step C has the following composition by mass percentage: Activated carbon 75%~85%; White clay 15%~25%.

2. A method for preparing a chlorhexidine organic acid salt according to claim 1, characterized in that, After the filtrate is cooled in step D, the process further includes conditioning, packaging and labeling steps to obtain a finished chlorhexidine gluconate solution.

3. A method for preparing a chlorhexidine organic acid salt according to claim 2, characterized in that, In step D, the filtrate is cooled and then tempered, and the tempering includes adjusting the chlorhexidine gluconate content in the chlorhexidine gluconate solution to be between 19 g / mL and 21 g / mL and the pH value to be between 5.5 and 7.

0.

4. A method for preparing a chlorhexidine organic acid salt according to claim 1, characterized in that: The composite adsorbent in step C has the following composition by mass percentage: Activated carbon 80%; white clay 20%.

5. The method for preparing a chlorhexidine organic acid salt according to any one of claims 1 to 4, characterized in that: The chlorhexidine base in step A is obtained by two-step condensation of biguanide and chlorhexidine hydrochloride, alkalization and crystallization.

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