Amino acid surfactant with hemostatic function and its synthesis method
By introducing short-chain fatty hydrocarbon groups and long-chain fatty acyl groups into the tranexamic acid matrix structure, the lipophilicity and transdermal permeability of amino acid surfactants are improved, solving the problem of insufficient hemostatic function in existing technologies. This achieves efficient hemostasis and good surface activity, making it suitable for wide application in daily chemical and medical hemostatic products.
Patent Information
- Application Number
- CN202411359758.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-27
- Publication Date
- 2025-12-16
- Estimated Expiration
- 2044-09-27
AI Technical Summary
Existing amino acid surfactants have shortcomings in hemostatic function and transdermal penetration, especially long-chain fatty acyl tracholate metal salts, which have poor water solubility and lipid solubility, making them difficult to widely apply in daily chemical and medical hemostatic products.
By introducing short-chain aliphatic hydrocarbon groups and long-chain aliphatic acyl groups into the tranexamic acid matrix structure, its lipophilicity and transdermal permeability are improved, and an amino acid surfactant with the structure of Formula 1 is prepared. Then, a specific synthetic method is used to carry out amidation and esterification reactions to improve its hemostatic function and surface activity.
It achieves good lipophilicity and transdermal penetration of amino acid surfactants, enhances their hemostatic effect and pigment dispersibility, and is suitable for daily chemical products and medical hemostatic products. Moreover, the preparation method is simple and low-cost, making it suitable for large-scale production.
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Figure CN119219517B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to a surfactant, particularly to an amino acid surfactant with hemostatic function, and also to its synthesis method, belonging to the field of fine chemical technology. Background Technology
[0002] Amino acid surfactants are a new type of green surfactant. They not only possess the properties of traditional surfactants, such as excellent emulsification, foaming, solubilization, wetting, and dispersion, but also exhibit good biodegradability, low toxicity, mild and non-irritating properties, and certain antibacterial activities. Currently, guided by the concept of green and safe development, amino acid surfactants are gradually replacing traditional surfactants and are widely used in daily chemical products, food, pharmaceuticals, and chemical industries. Although amino acid surfactants have made significant progress in many fields as an upgraded product of traditional surfactants, research and development of functional amino acid surfactants is still limited, indicating a huge potential for future development.
[0003] Tranexamic acid, also known as tranexamic acid, is chemically named trans-4-aminomethylcyclohexanecarboxylic acid. It exerts its hemostatic effect by inhibiting fibrinolysis and is a classic hemostatic agent used in surgery. Its efficacy is definite and its safety is high, making it widely used clinically for hemostasis after trauma or surgery. Tranexamic acid also has applications in daily chemical products; for example, it is used as an additive in toothpaste with hemostatic properties. However, when solutions or creams containing tranexamic acid are applied topically, due to its strong hydrophilicity and hydrogen bonding, it is difficult for tranexamic acid to penetrate the skin's stratum corneum barrier. Therefore, structural modification of tranexamic acid is often necessary to improve its transdermal permeability and enhance its efficacy. For example, Chinese patent CN 101253148A discloses an acylalkyl carbamate of trans-4-(aminomethyl)-cyclohexanecarboxylic acid as a prodrug for treating bleeding or skin diseases; Chinese patent CN 105085364A discloses a tranexamic acid derivative prepared from maleic anhydride and tranexamic acid; Chinese patent CN 113952326A discloses polyethylene glycol-modified tranexamic acid and its preparation method, which can effectively prolong the efficacy of tranexamic acid and reduce the frequency of medication for patients during long-term use. Chinese patent CN 117342971A discloses a class of fatty acyl tranexamic acid metal salts and their preparation method, which are applied in the pharmaceutical and daily chemical fields, combining surfactants and coagulation properties; however, the water solubility and lipid solubility of this class of long-chain fatty acyl tranexamic acid metal salts are both very poor. Summary of the Invention
[0004] In view of the shortcomings of existing amino acid surfactants, the purpose of this invention is to provide an amino acid surfactant with hemostatic function, which has both good surface activity and hemostatic function, and can be widely used in daily chemical products and medical hemostatic products. Compared with the long-chain fatty acyl tranexamic acid salts reported in the prior art, it has good lipid solubility, better transdermal penetration and better pigment dispersibility.
[0005] The second objective of this invention is to provide a method for preparing an amino acid surfactant with hemostatic function. This method is simple to operate, operates under mild conditions, is low in cost, and is conducive to large-scale production.
[0006] To achieve the above technical objectives, the present invention provides an amino acid surfactant with hemostatic function, having the structure shown in Formula 1:
[0007]
[0008] in,
[0009] R1 is a C1-C4 alkane group;
[0010] R2 is C7~C 17 Aliphatic hydrocarbon groups.
[0011] The hemostatic amino acid surfactant of the present invention uses tranexamic acid as the parent structure, and introduces short-chain aliphatic hydrocarbon groups on its carboxyl group and long-chain aliphatic acyl groups on its amino group. It was unexpectedly discovered that not only is its hemostatic effect superior to that of tranexamic acid, but the introduction of its long-chain aliphatic acyl groups endows it with good emulsifying and dispersing functions, while the introduction of short-chain aliphatic hydrocarbon groups reduces the hydrophilicity of the carboxyl group, improves its lipid solubility, and improves its skin permeability, thus giving it better surface activity and hemostatic function.
[0012] In the structure of Formula 1 of the present invention, R2 is a common long-chain aliphatic hydrocarbon group, and R2 is further preferably C7~C8. 17 Straight-chain alkyl groups, or C7-C6 groups 17 Branched alkyl groups, or C7-C6 groups containing one or two double bonds. 17 Alkenyl groups. Specific examples include octyl, dodecyl, etc.
[0013] As a preferred embodiment, in the structure of Formula 1, R1 is methyl, ethyl, propyl, isopropyl, or butyl. R1 can only be a low-carbon aliphatic group; if the carbon chain of R1 is too long, it will lose its surfactant function.
[0014] This invention also provides a method for synthesizing an amino acid surfactant with hemostatic function. The method involves fully dissolving tranexamic acid or tranexamic acid salt, alkali, organic co-solvent, and water, cooling the solution to below 10°C, and slowly adding fatty acyl chloride dropwise to carry out an amidation reaction. Simultaneously, an alkaline solution is used to maintain the pH of the reaction system. After the fatty acyl chloride is added, the reaction continues for more than 1 hour. The reaction solution is then transferred to a dilute acid solution to precipitate. The precipitate is mixed evenly with an alcohol, and an acid catalyst is added to catalyze an esterification reaction. After the reaction is completed, the alcohol is recovered by distillation and then extracted and separated to obtain the target product.
[0015] The fatty acyl chloride has the structure shown in Formula 2:
[0016]
[0017] The alcohols are C1 to C4 monohydric alcohols.
[0018] As a preferred embodiment, the base is 0.5 to 1.5 times the molar amount of tranexamic acid or tranexamic acid salt. The tranexamic acid salt is, for example, a sodium salt.
[0019] As a preferred embodiment, the mass of the tranexamic acid or tranexamic acid salt is 5-15% of the mass of water.
[0020] As a preferred embodiment, the organic co-solvent is 5-15% of the mass of water.
[0021] As a preferred embodiment, the organic co-solvent includes acetone and / or ethanol; acetone is most preferred. Introducing a co-solvent improves the solubility of tranexamic acid or tranexamic acid salts in water.
[0022] As a preferred embodiment, the base is at least one selected from sodium hydroxide, potassium hydroxide, and triethylamine. Sodium hydroxide is the most preferred.
[0023] As a preferred embodiment, the molar amount of fatty acyl chloride is 0.8 to 1.2 times the molar amount of tranexamic acid or tranexamic acid salt.
[0024] As a preferred embodiment, the acid catalyst is sulfuric acid.
[0025] As a preferred embodiment, the esterification reaction is carried out under the following conditions: at reflux temperature, for 6 to 12 hours.
[0026] The method for synthesizing the amino acid surfactant with hemostatic function of the present invention is as follows:
[0027]
[0028] Compared with existing technologies, the beneficial technical effects of the present invention are as follows:
[0029] The amino acid surfactant with hemostatic function provided by this invention has both surface activity and hemostatic function. Compared with long-chain fatty acyl tranexamic acid metal salts, it has good lipophilicity, better transdermal penetration and good pigment dispersibility. It is expected to be used as an additive in daily chemical products and medical hemostatic products with hemostatic effect.
[0030] The method for preparing an amino acid surfactant with hemostatic function provided by this invention is simple to operate, has mild conditions, low cost, and is conducive to large-scale production. Attached Figure Description
[0031] Figure 1 This is the 1H NMR spectrum of N-lauroyl tranexamic acid.
[0032] Figure 2 This is the 1H NMR spectrum of N-lauroyl tranexamic acid ethyl ester.
[0033] Figure 3 This is the 1H NMR spectrum of isopropyl lauroyl tranexamic acid.
[0034] Figure 4 The transdermal absorption curves of different compounds are shown. Detailed Implementation
[0035] The following specific embodiments are intended to further illustrate the content of the present invention, rather than to limit the scope of protection of the claims.
[0036] Example 1
[0037] Add 90 mL of water to the reaction vessel, then add 1.40 g of sodium hydroxide and dissolve 9.43 g of tranexamic acid. Add 12 mL of acetone and continue stirring while cooling to 10 °C. Slowly add 11.97 g of lauroyl chloride dropwise, while maintaining the current pH value with a 30% sodium hydroxide aqueous solution. After the addition is complete, continue stirring for 1 hour, then transfer to a hydrochloric acid aqueous solution and stir for another 1 hour. A white solid precipitates, which is filtered, washed with water, and dried to obtain 17.51 g of high-purity white solid product, with a yield of 94%. 1 H NMR (400MHz, d) 6 -DMSO) δ12.00(brs,1H),7.74(s,1H),2.87(t,J=8.0Hz,2H),2.12–2.05(m,1H),2.03(t,J=8.0Hz,2H),1.8 8(d,J=12.0Hz,2H),1.70(d,J=12.0Hz,2H),1.50–1.42(m,2H),1.31–1.16(m,19H),0.93–0.83(m,5H)ppm.
[0038] Example 2
[0039] Add 90 mL of water to the reaction vessel, then add 1.40 g of sodium hydroxide and dissolve 9.43 g of tranexamic acid. Next, add 12 mL of acetone and continue stirring while cooling to 15 °C. Slowly add 11.97 g of lauroyl chloride dropwise, while maintaining the current pH value with a 30% sodium hydroxide aqueous solution. After the addition is complete, continue stirring for 1 hour, then transfer to a hydrochloric acid aqueous solution and stir for another 1 hour. A white solid precipitates out. Filter, wash with water, and dry to obtain 17.09 g of high-purity white solid product, with a yield of 92%.
[0040] Example 3
[0041] Add 90 mL of water to the reaction vessel, then add 1.40 g of sodium hydroxide and dissolve 9.43 g of tranexamic acid. Next, add 12 mL of ethanol and continue stirring while cooling to 10 °C. Slowly add 11.97 g of lauroyl chloride dropwise, while maintaining the current pH value with a 30% sodium hydroxide aqueous solution. After the addition is complete, continue stirring for 1 hour, then transfer to a hydrochloric acid aqueous solution and stir for another 1 hour. A white solid precipitates out. Filter, wash with water, and dry to obtain 15.02 g of high-purity white solid product, with a yield of 81%.
[0042] Example 4
[0043] Add 90 mL of water to the reaction vessel, then add 2.00 g of potassium hydroxide and dissolve 9.43 g of tranexamic acid. Add 12 mL of acetone, continue stirring, and cool to 10 °C. Slowly add 11.97 g of lauroyl chloride dropwise, while maintaining the current pH value with a 30% potassium hydroxide aqueous solution. After the addition is complete, continue stirring for 1 hour, then transfer to a hydrochloric acid aqueous solution and stir for another 1 hour. A white solid precipitates, which is filtered, washed with water, and dried to obtain 16.81 g of high-purity white solid product, with a yield of 91%.
[0044] Example 5
[0045] Add 90 mL of water to the reaction vessel, then add 1.40 g of sodium hydroxide and dissolve 9.43 g of tranexamic acid. Add 12 mL of acetone, continue stirring, and cool to 10 °C. Slowly add 13.12 g of lauroyl chloride dropwise, while maintaining the current pH value with a 30% sodium hydroxide aqueous solution. After the addition is complete, continue stirring for 1 hour, then transfer to a hydrochloric acid aqueous solution and stir for another 1 hour. A white solid precipitates, which is filtered, washed with water, and dried to obtain 17.80 g of high-purity white solid product, with a yield of 87%.
[0046] Example 6
[0047] Add 90 mL of water to the reaction vessel, then add 1.40 g of sodium hydroxide and dissolve 9.43 g of tranexamic acid. Add 12 mL of acetone and continue stirring while cooling to 10 °C. Slowly add 14.43 g of lauroyl chloride dropwise, while maintaining the current pH value with a 30% sodium hydroxide aqueous solution. After the addition is complete, continue stirring for 1 hour, then transfer to a hydrochloric acid aqueous solution and stir for another 1 hour. A white solid precipitates out. Filter, wash with water, and dry to obtain 18.66 g of high-purity white solid product, with a yield of 92%.
[0048] Example 7
[0049] Add 90 mL of water to the reaction vessel, then add 1.40 g of sodium hydroxide and dissolve 9.43 g of tranexamic acid. Add 12 mL of acetone and continue stirring while cooling to 10 °C. Slowly add 10.41 g of octanoyl chloride dropwise, maintaining the pH value with a 30% sodium hydroxide aqueous solution. After the addition is complete, continue stirring for 1 hour, then transfer to a hydrochloric acid aqueous solution and stir for another 1 hour. A white solid precipitates, which is filtered, washed with water, and dried to obtain 15.52 g of a high-purity white solid product, with a yield of 91%.
[0050] Example 8
[0051] Add 90 mL of water to the reaction vessel, then add 1.40 g of sodium hydroxide and dissolve 9.43 g of tranexamic acid. Add 12 mL of acetone and continue stirring while cooling to 10 °C. Slowly add 12.21 g of decanoyl chloride dropwise, while maintaining the current pH value with a 30% sodium hydroxide aqueous solution. After the addition is complete, continue stirring for 1 hour, then transfer to a hydrochloric acid aqueous solution and stir for another 1 hour. A white solid precipitates, which is filtered, washed with water, and dried to obtain 17.17 g of a high-purity white solid product, with a yield of 92%.
[0052] Example 9
[0053] Add 90 mL of water to the reaction vessel, then add 1.40 g of sodium hydroxide and dissolve 9.43 g of tranexamic acid. Add 12 mL of acetone and continue stirring while cooling to 10 °C. Slowly add 15.04 g of palmitoyl chloride dropwise, maintaining the pH value with a 30% sodium hydroxide aqueous solution. After the addition is complete, continue stirring for 1 hour, then transfer to a hydrochloric acid aqueous solution and stir for another 1 hour. A white solid precipitates, which is filtered, washed with water, and dried to obtain 21.95 g of a high-purity white solid product, with a yield of 93%.
[0054] Example 10
[0055] Add 90 mL of water to the reaction vessel, then add 1.40 g of sodium hydroxide and dissolve 9.43 g of tranexamic acid. Add 12 mL of acetone, continue stirring, and cool to 10 °C. Slowly add 13.92 g of cocoyl chloride dropwise, while maintaining the current pH value with a 30% sodium hydroxide aqueous solution. After the addition is complete, continue stirring for 1 hour, then transfer to a hydrochloric acid aqueous solution and stir for another 1 hour. A white solid precipitates, which is filtered, washed with water, and dried to obtain 19.28 g of high-purity white solid product, with a yield of 95%.
[0056] The methods for preparing long-chain tranexamic acid esters from the long-chain tranexamic acid obtained in Examples 1 to 10 via esterification are all similar. The following description uses N-lauroyl tranexamic acid as an example.
[0057] Example 11
[0058] 6.79 g of N-lauroyl tranexamic acid prepared in Example 1 and 40 mL of ethanol were added to a 100 mL round-bottom flask and stirred until homogeneous. Then, 0.01 g of concentrated sulfuric acid (5 mol%) was added, and an esterification reaction dehydration apparatus (molecular sieve dehydration) was set up. The mixture was heated under reflux for 6 h, then heating was stopped and the mixture was cooled to room temperature. Most of the ethanol was recovered by vacuum distillation of the reaction solution. 50 mL of ethyl acetate was added, and the mixture was transferred to a separatory funnel. The organic phase was washed successively with 20 mL of water, 10% sodium bicarbonate solution, water, and saturated brine. After drying with anhydrous sodium sulfate, the solvent was removed by vacuum distillation to obtain 6.22 g of ethyl N-lauroyl tranexamic acid product, with a yield of 85%. 1 H NMR (400MHz, CDCl3) δ5.61(brs,1H),4.09(q,J=8.0Hz,2H),3.09(t,J=8.0Hz,2H),2.15(t,J=8.0Hz,2H),1.98(dd,J=12.0Hz,4.0Hz,2H),1 .80(dd,J=12.0Hz,4.0Hz,2H),1.60(t,J=8.0Hz,2H),1.44–1.33(m,4H),1.28–1.21(m,19H),1.00–0.93(m,2H),0.86(t,J=8.0Hz,3H)ppm.
[0059] Example 12
[0060] 6.79 g of N-lauroyl tranexamic acid prepared in Example 1 and 50 mL of isopropanol were added to a 100 mL round-bottom flask and stirred until homogeneous. Then, 0.01 g of concentrated sulfuric acid (5 mol%) was added, and an esterification reaction dehydration apparatus (molecular sieve dehydration) was set up. The mixture was heated under reflux for 8 h, then heating was stopped and the mixture was cooled to room temperature. Most of the ethanol in the reaction solution was recovered by vacuum distillation. 50 mL of ethyl acetate was added, and the mixture was transferred to a separatory funnel. The organic phase was washed successively with 20 mL of water, 10% sodium bicarbonate solution, water, and saturated brine. After drying with anhydrous sodium sulfate, the solvent was removed by vacuum distillation to obtain 6.19 g of isopropyl N-lauroyl tranexamic acid product, with a yield of 81%. 1 HNMR (400MHz, CDCl3) δ5.62(brs,1H),4.99–4.93(m,1H),3.09(t,J=8.0Hz,2H),2.15(t,J=8.0Hz,2H),1.97(dd,J=12.0Hz,4.0Hz,2H),1.80(dd,J=1 2.0Hz,4.0Hz,2H),1.60(t,J=8.0Hz,2H),1.48–1.32(m,4H),1.26–1.21(m ,16H),1.20(d,J=4.0Hz,6H),1.00–0.90(m,2H),0.86(t,J=8.0Hz,3H)ppm.
[0061] Example 13
[0062] Comparative test of the hemostatic function of N-lauroyl tranexamic acid ethyl ester and N-lauroyl tranexamic acid sodium ester obtained in Example 11:
[0063] Experimental Methods: Forty-two qualified ICR mice (half male and half female, weighing 20.4–25.6 g) were selected and randomly divided into four groups according to sex and weight: a model control group, test substance groups 1, 2, and 3, and N-lauroyl tranexamic acid control groups 1, 2, and 3, with six mice in each group. Mice were fixed in a mouse cage, and different concentrations of the test sample or physiological saline were administered 2 cm from the tail tip. The administration time was 30 minutes, and the administration was repeated once after a 4-hour interval. Thirty minutes after the last administration, the tail was cut 1.5 cm from the tip using ophthalmic scissors. Bleeding time was recorded as soon as blood flowed out naturally. Every 10 seconds, a pre-weighed cotton ball was used to absorb blood droplets until bleeding stopped naturally (no blood was absorbed when the cotton ball was used). The weight of the blood-stained cotton ball was measured. The tail-cutting bleeding time was recorded, and the amount of bleeding in each group was calculated.
[0064] (2) Dosage design: See Table 1 for sample dosage details.
[0065] Table 1. Trial grouping and dosage design
[0066]
[0067] (3) Experimental results:
[0068] (a) Effect on hemorrhage volume in ICR mice
[0069] As shown in Table 2, compared with the model control group, the amount of tail tip hemorrhage in the test substance group 2 was significantly reduced (P<0.05), while there was no statistically significant difference in the amount of tail tip hemorrhage between the test substance groups 1 and 3 (P>0.05).
[0070] Table 2. Bleeding volume in mice of each group ( n=6)
[0071]
[0072] (b) Effect on bleeding time in ICR mice
[0073] As shown in Table 3, compared with the model control group, the bleeding time of test substance group 2 was significantly reduced (P<0.01), while there was no statistically significant difference in the tail tip bleeding time between test substance groups 1 and 3 (P>0.05).
[0074] Table 3 Bleeding time of mice in each group ( n=6)
[0075]
[0076] (4) Conclusion and Evaluation
[0077] To investigate and compare the hemostatic effects of different concentrations of the test substance with those of sodium N-lauroyl tranexamate, this study used normal ICR mice and administered different concentrations of the test substance via tail contact. The mice were then tail-dislocated, and the amount and duration of bleeding were observed to study the hemostatic effects of different concentrations of the test substance. The results showed that, using the tail immersion contact method, a 0.24% concentration of the test substance significantly reduced tail bleeding and shortened bleeding time in ICR mice, demonstrating a significantly better hemostatic effect compared to tranexamic acid.
[0078] Example 14
[0079] Surface tension test of N-lauroyl tranexamic acid ester obtained in Example 11:
[0080] (1) Experimental method: According to GB / T 22237-2008 standard, the sample aqueous solution was prepared using double distilled water. The sample amount was 0.5g and the sample test concentration was 0.5g / 100ml. Three parallel preparations were made. After standing at 20℃ for 1 hour, the surface tension of the aqueous solution was determined by the ring method.
[0081] (2) Experimental Design
[0082] Table 4 Experimental Design
[0083]
[0084] (3) Experimental results: As shown in Table 5, the test sample N-lauroyl tranexamic acid ethyl ester has a significant ability to reduce the surface tension of liquids.
[0085] Table 5 Experimental Results
[0086]
[0087] (4) Conclusion and Evaluation:
[0088] To examine the surface activity of this product, the surface tension of its aqueous solution was measured to determine its surface activity performance. The experimental results show that this product has good surface activity.
[0089] Example 15
[0090] Referring to Examples 11 and 12, the prepared N-lauroyl tranexamic acid ethyl ester and N-lauroyl tranexamic acid isopropyl ester were applied to the following formulation Table 1 as experimental groups, and compared with the control groups of N-lauroyl tranexamic acid sodium and tranexamic acid using the modified Franz assay.
[0091] Table 6
[0092]
[0093] In vitro transdermal absorption test: The abdominal skin of Kunming mice was used as the permeating skin. Mice of similar weight were selected, the long hair on the abdomen was cut off, the hair was washed and removed, and after being fed for 24 hours, they were slaughtered and the skin was taken. The subcutaneous fat was removed, and after being washed with sterile physiological saline, the skin was placed in a diffusion cell for evaluation.
[0094] Experimental method: A modified Franz apparatus was used (receiving cell volume of 14.5 ml, effective contact surface of the receiving cell of 4.14 cm). 2For each sample collection, 4.0g of mouse skin was placed on the Franz cell, with the dermal side facing the receiving cell. The skin was covered, ensuring no air bubbles were present. A plastic rope was used to wrap and secure the skin around the opening to prevent leakage of the receiving fluid. Excess skin was removed. The experimental sample (4.0g) was then placed tightly against the stratum corneum of the extracted mouse skin. The top of the release cell was sealed with a plastic film. A modified Franz device was used in the same manner, with the control group (4.0g) placed tightly against the stratum corneum of the extracted mouse skin as a blank control. The sample was kept at 37°C with constant electromagnetic stirring. At 0, 1, 2, 3, 4, 5, 6, and 10 hours, 4ml of receiving fluid was collected from both the sample and blank receiving cells, and 50% ethanol saline was added to each. The collected receiving fluid was filtered through a microporous membrane, and 20ul was injected into a high-performance liquid chromatograph (HPLC) for analysis. The cumulative permeate (Q) was calculated based on the peak area. An in vitro transdermal absorption curve was plotted with time (t) on the x-axis. Figure 3 .
[0095] Conclusions and Evaluation:
[0096] The experimental results show that the cumulative permeability of N-lauroyl tranexamic acid ethyl ester and isopropyl ester is significantly greater than that of long-chain fatty acyl tranexamic acid sodium salt and tranexamic acid, indicating that this product has excellent transdermal permeability.
[0097] Example 16
[0098] Lipid solubility test of N-lauroyl tranexamic acid ethyl ester obtained in Example 11:
[0099] (1) Experimental method: According to the SN / T2879-2011 standard, the analyte was dissolved in liquid standard fat (triglyceride mixture HB307) by stirring. The analyte was continuously added until the analysis showed that its mass fraction reached a constant value, which is the saturated mass fraction of the analyte.
[0100] (1) Experimental results:
[0101] Table 7 Results of lipid solubility of substances
[0102]
[0103] As shown in Table 7, the tested samples N-lauroyl tranexamic acid ethyl ester and N-lauroyl tranexamic acid isopropyl ester exhibit significant lipophilicity.
Claims
1. An amino acid surfactant with hemostatic function, characterized in that: It has the structure shown in Equation 1: ; in, R1 is methyl, ethyl, propyl, isopropyl, or butyl; R2 is C7~C 17 Straight-chain alkyl groups, or C7-C6 groups 17 Branched alkyl groups, or C7-C6 groups containing one or two double bonds. 17 The alkenyl group.
2. The method for synthesizing an amino acid surfactant with hemostatic function as described in claim 1, characterized in that: After fully dissolving tranexamic acid or tranexamic acid salt, alkali, organic co-solvent, and water, the mixture is cooled to below 10°C, and fatty acyl chloride is slowly added dropwise to carry out the amidation reaction. At the same time, the pH of the reaction system is maintained by alkali solution. After the fatty acyl chloride is added dropwise, the reaction continues for more than 1 hour. Then, the reaction solution is transferred to dilute acid solution to precipitate the precipitate. After the precipitate is mixed evenly with alcohol, an acid catalyst is added to catalyze the esterification reaction. After the reaction is completed, the alcohol is recovered by distillation and then extracted and separated to obtain the target product. The fatty acyl chloride has the structure shown in Formula 2: ; Where R2 is C7~C 17 Straight-chain alkyl groups, or C7-C6 groups 17 Branched alkyl groups, or C7-C6 groups containing one or two double bonds. 17 alkenyl groups; The alcohols are methanol, ethanol, propanol, isopropanol, or butanol.
3. The method for synthesizing an amino acid surfactant with hemostatic function according to claim 2, characterized in that: The base is 0.5 to 1.5 times the molar amount of tranexamic acid or tranexamic acid salt; The mass of the tranexamic acid or tranexamic acid salt is 5-15% of the mass of water; The organic co-solvent is 5-15% of the mass of water.
4. The method for synthesizing an amino acid surfactant with hemostatic function according to claim 3, characterized in that: The organic co-solvent includes acetone and / or ethanol; The alkali is at least one of sodium hydroxide, potassium hydroxide, and triethylamine.
5. The method for synthesizing an amino acid surfactant with hemostatic function according to claim 2, characterized in that: The molar amount of fatty acyl chloride is 0.8 to 1.2 times the molar amount of tranexamic acid.
6. The method for synthesizing an amino acid surfactant with hemostatic function according to claim 2, characterized in that: The acid catalyst is sulfuric acid.
7. The method for synthesizing an amino acid surfactant with hemostatic function according to claim 2, characterized in that: The esterification reaction is carried out under the following conditions: at reflux temperature, for 6 to 12 hours.
Citation Information
Patent Citations
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