Cupping spray and preparation method thereof
By using modified surfactants and a variety of traditional Chinese medicinal materials in cupping sprays, combined with absorption accelerators and deionized water, the problem of easy precipitation of existing cupping sprays has been solved, and the stability and efficacy of the medicine liquid have been improved.
Patent Information
- Application Number
- CN202411944730.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-27
- Publication Date
- 2025-03-11
- Estimated Expiration
- 2044-12-27
AI Technical Summary
The existing cupping spray has complex ingredients, which is prone to precipitation and affects the efficacy of the medicine.
A stable cupping spray is prepared by specific chemical reaction steps using modified surfactants, combined with a variety of Chinese herbal medicines, added absorption accelerator and deionized water.
Modified surfactants improve the dissolution performance of the spray in water, prevent precipitation, maintain the clarity of the drug solution, extend the stability of the drug solution, facilitate long-term storage, and enhance the efficacy of the drug.
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Abstract
Description
Technical Field
[0001] The invention relates to the technical field of sprays, and in particular to a cupping spray and a preparation method thereof. Background Art
[0002] Cupping is a traditional Chinese medicine treatment method. It uses the method of burning fire to extract air to generate negative pressure in the cup, thereby stimulating local acupuncture points, achieving the effects of dredge tendons and activate collaterals, promote qi and blood circulation, reduce swelling and relieve pain, and dispel wind and cold. When cupping treatment is performed, medicine will be sprayed on the acupuncture points to further enhance the efficacy of cupping. Cupping spray is made by soaking a variety of Chinese medicines, with complex ingredients and easy precipitation, which is not conducive to the efficacy of the medicine. Surfactant is an auxiliary agent with a very significant solubilizing effect. It can reduce the surface tension between the solvent and the poorly soluble drug, maintain the wet state of the drug, ensure that the solid drug remains moist, effectively prevent the floating or sedimentation of the drug medium powder, and make the drug liquid have excellent clarity, which is conducive to the storage and management of medicinal materials. Therefore, in the production process of Chinese medicine spray, it is particularly important to add a suitable surfactant. Summary of the invention
[0003] In view of the shortcomings of the prior art, the present invention aims to provide a cupping spray and a preparation method thereof.
[0004] To achieve the above object, the present invention is implemented through the following technical solutions:
[0005] A cupping spray comprising the following raw materials in parts by weight:
[0006] Angelica: 30-40 servings,
[0007] Frankincense: 15-20 parts,
[0008] Asarum: 30-40 servings,
[0009] Saffron: 10-20 parts,
[0010] Yuanhu: 15-25 parts,
[0011] Chuanxiong: 12-18 parts,
[0012] Buddleja buddha: 20-26 parts,
[0013] Thunbergia truncatula: 10-18 parts,
[0014] Panax notoginseng: 5-15 servings,
[0015] Purple salvia: 20-30 portions,
[0016] Processed Radix Aconiti Kusnezoffii: 14-22 servings,
[0017] Millettia reticulata: 18-26 servings,
[0018] Dragon's blood: 15-30 portions,
[0019] Borneol: 15-20 parts,
[0020] Modified surfactant: 4-8 parts,
[0021] Absorption enhancer: 8-12 parts,
[0022] Deionized water: 300 parts;
[0023] The modified surfactant is prepared by the following method:
[0024] S1: Anhydrous ethanol, octadecyl dimethyl tertiary amine and concentrated hydrochloric acid are added to the reactor in sequence, stirred and mixed at room temperature, and then epichlorohydrin is added, and the temperature is raised and refluxed for reaction for 2-4 hours to obtain (3-chloro-2-hydroxypropyl) octadecyl dimethyl ammonium chloride;
[0025] S2: Anhydrous ethanol, (3-chloro-2-hydroxypropyl) octadecyl dimethyl ammonium chloride, and 2-(dimethylamino) dodecyl propionate hydrochloride are added to the reactor in sequence, stirred and mixed at room temperature, and heated to reflux for reaction for 20-28 hours to obtain intermediate 1;
[0026] S3: Under nitrogen protection, toluene, allyl succinic anhydride and intermediate 1 are added to the reactor in sequence, stirred and mixed, heated to 60-70°C, kept warm for 0.5-1.5h, then heated to 80°C, and then tetraisopropyl titanate catalyst was added, kept warm for 10-15min, and then heated to 90-100°C, reacted for 3-5h, to obtain intermediate 2;
[0027] S4: Under nitrogen protection, tetrahydrofuran, intermediate 2, and azobisisobutyronitrile are added to a reaction container in sequence, stirred and mixed, heated to 50-60° C., and reacted for 14-18 hours to obtain a modified surfactant.
[0028] The number average molecular weight of the modified surfactant is 20,000-32,000.
[0029] In step S1, the mass ratio of anhydrous ethanol, octadecyl dimethyl tertiary amine, epichlorohydrin and concentrated hydrochloric acid is 80:(12-18):(12-16):(2-4).
[0030] In step S2, the mass ratio of anhydrous ethanol, (3-chloro-2-hydroxypropyl) octadecyl dimethyl ammonium chloride, and 2-(dimethylamino) dodecyl propionate hydrochloride is 80:(18-22):(16-18).
[0031] In step S3, the mass ratio of toluene, allyl succinic anhydride, intermediate 1, and catalyst tetraisopropyl titanate is 300:10:(170-180):(0.03-0.05).
[0032] In step S4, the mass ratio of tetrahydrofuran, intermediate 2 and azobisisobutyronitrile is 30:(8-10):(0.016-0.018).
[0033] The absorption enhancer is laurocapram.
[0034] A method for preparing a cupping spray comprises the following steps:
[0035] (1) Weigh the following raw materials by weight: 30-40 parts of Angelica sinensis, 15-20 parts of frankincense, 30-40 parts of asarum, 10-20 parts of saffron, 15-25 parts of Corydalis yanhusuo, 12-18 parts of Chuanxiong, 20-26 parts of Buddleja buddleja, 10-18 parts of Herba scutellariae, 5-15 parts of Panax notoginseng, 20-30 parts of Salvia miltiorrhizae, 14-22 parts of Radix Aconiti Kusnezoffii, 18-26 parts of Millettia reticulatae, 15-30 parts of Sanguisorba officinalis, 4-8 parts of modified surfactant, 8-12 parts of absorption enhancer, and 300 parts of deionized water;
[0036] (2) soaking the raw material weighed in step (1) in 3000 parts by weight of 60° kaoliang wine, and after 25-30 days, filtering and retaining the soaking liquid;
[0037] (3) placing the infusion prepared in step (2) into a container and heating it to 60-80° C. for 2-8 minutes to obtain a medicinal solution;
[0038] (4) Add red yeast rice and 15-20 parts by weight of borneol to the medicinal solution prepared in step (3), wherein the weight ratio of the medicinal solution to red yeast rice is 10:1, and then ferment in a porcelain jar at room temperature for 20-30 days to obtain a cupping spray.
[0039] Due to the adoption of the above technical solution, the beneficial effects of the present invention include:
[0040] (1) The present invention uses octadecyl dimethyl tertiary amine and epichlorohydrin to react to prepare (3-chloro-2-hydroxypropyl) octadecyl dimethyl ammonium chloride, then (3-chloro-2-hydroxypropyl) octadecyl dimethyl ammonium chloride and 2-(dimethylamino) propionic acid dodecyl hydrochloride to react to prepare intermediate 1, then intermediate 1 is reacted with allyl succinic anhydride to prepare intermediate 2, and finally intermediate 2 is polymerized to prepare a modified surfactant.
[0041] (2) The modified surfactant prepared by the present invention contains both quaternary ammonium ions and alkane chains in its molecular structure. The quaternary ammonium ions give it hydrophilicity, making it easy to enter the aqueous phase environment; while the alkane chains give it hydrophobicity, making it able to bind to drug molecules; at the same time, the surfactant is an oligomeric surfactant. Compared with traditional monomeric surfactants, the hydrophobic alkyl chains are more likely to produce strong interactions, and the repulsive force between the hydrophilic groups is also greatly weakened, making the molecular arrangement more compact, and thus having higher surface activity; in addition, the ester group introduced during the modification process also promotes the binding ability of the surfactant with the drug. As a result, the solubility of the spray in water is improved, and the problem of precipitation of the spray during long-term storage is solved. DETAILED DESCRIPTION
[0042] The invention will be further described below in conjunction with the embodiments, but the invention is not limited to these embodiments.
[0043] Example 1 Preparation of modified surfactant:
[0044] S1: 80g of anhydrous ethanol, 12g of octadecyl dimethyl tertiary amine, and 2g of concentrated hydrochloric acid (12mol / L) were added to the reactor in sequence, stirred and mixed at room temperature, and then 12g of epichlorohydrin was added. The temperature was raised and refluxed for 4h. After the reaction was completed, the reaction was carried out by reduced pressure distillation at 60℃ for 1h and vacuum drying at 50℃ for 6h to obtain (3-chloro-2-hydroxypropyl) octadecyl dimethyl ammonium chloride. The reaction equation is as follows:
[0045]
[0046] S2: 80 g of anhydrous ethanol, 18 g of (3-chloro-2-hydroxypropyl) octadecyl dimethyl ammonium chloride, and 16 g of 2-(dimethylamino) propionate dodecyl hydrochloride were added to the reactor in sequence, stirred and mixed at room temperature, and heated to reflux for 28 h. After the reaction was completed, the mixture was distilled at 60° C. under reduced pressure for 1 h, and vacuum dried at 50° C. for 6 h to obtain intermediate 1, the reaction equation of which is shown as follows:
[0047]
[0048] S3: Under nitrogen protection, 300g toluene, 10g allyl succinic anhydride, and 170g intermediate 1 were added to the reactor in sequence, stirred and mixed, heated to 60°C, kept warm for 1.5h, then heated to 80°C, and then 0.03g catalyst tetraisopropyl titanate was added, kept warm for 15min, and then heated to 90°C. The water generated during the reaction was separated by a water separator, and the reaction was carried out for 5h. After the reaction was completed, it was washed with 200g deionized water, and then dried with 200g anhydrous sodium sulfate for 2h, distilled at 60°C under reduced pressure for 1h, and vacuum dried at 60°C for 6h to obtain intermediate 2. The reaction equation is shown as follows:
[0049]
[0050] S4: Under nitrogen protection, 60g of tetrahydrofuran, 16g of intermediate 2, and 0.032g of azobisisobutyronitrile were added to the reaction container in sequence, stirred and mixed, heated to 50°C, and reacted for 18h. After the reaction, 100g of deionized water was added for washing, and then dried with 100g of anhydrous sodium sulfate for 2h, distilled under reduced pressure at 65°C for 1h, and vacuum dried at 50°C for 6h to obtain a modified surfactant with a number average molecular weight of 20490. The reaction equation is shown as follows:
[0051]
[0052] Example 2 Preparation of modified surfactant:
[0053] S1: 80g of anhydrous ethanol, 16g of octadecyl dimethyl tertiary amine, and 3g of concentrated hydrochloric acid (12mol / L) were added to the reactor in sequence, stirred and mixed at room temperature, and then 14g of epichlorohydrin was added, and the temperature was raised to reflux for reaction for 3h. After the reaction was completed, the reaction was carried out by reduced pressure distillation at 60℃ for 1.5h, and vacuum drying at 60℃ for 5h to obtain (3-chloro-2-hydroxypropyl) octadecyl dimethyl ammonium chloride;
[0054] S2: 80 g of anhydrous ethanol, 20 g of (3-chloro-2-hydroxypropyl) octadecyl dimethyl ammonium chloride, and 17 g of 2-(dimethylamino) propionic acid dodecyl hydrochloride were added to the reactor in sequence, stirred and mixed at room temperature, and heated to reflux for 24 h. After the reaction was completed, the mixture was distilled at 60° C. under reduced pressure for 1.5 h, and dried under vacuum at 60° C. for 5 h to obtain intermediate 1;
[0055] S3: Under nitrogen protection, 300 g toluene, 10 g allyl succinic anhydride, and 175 g intermediate 1 were added to the reactor in sequence, stirred and mixed, heated to 65°C, kept warm for 1 hour, then heated to 80°C, and then 0.04 g catalyst tetraisopropyl titanate was added, kept warm for 13 minutes, and then heated to 95°C. The water generated during the reaction was removed by a water separator, reacted for 4 hours, washed with 200 g deionized water after the reaction was completed, and then dried with 200 g anhydrous sodium sulfate for 2 hours, distilled at 60°C under reduced pressure for 1.5 hours, and vacuum dried at 60°C for 5 hours to obtain intermediate 2;
[0056] S4: Under nitrogen protection, 60 g of tetrahydrofuran, 18 g of intermediate 2 and 0.034 g of azobisisobutyronitrile were added to the reaction container in sequence, stirred and mixed, and the temperature was raised to 55°C for reaction for 16 h. After the reaction, 100 g of deionized water was added for washing, and then dried with 100 g of anhydrous sodium sulfate for 2 h, distilled under reduced pressure at 65°C for 1.5 h, and vacuum dried at 60°C for 5 h to obtain a modified surfactant with a number average molecular weight of 26920.
[0057] Example 3 Preparation of modified surfactant:
[0058] S1: 80g of anhydrous ethanol, 18g of octadecyl dimethyl tertiary amine, and 4g of concentrated hydrochloric acid (12mol / L) were added to the reactor in sequence, stirred and mixed at room temperature, and then 16g of epichlorohydrin was added, and the temperature was raised to reflux for reaction for 2h. After the reaction was completed, the reaction was carried out by vacuum distillation at 60℃ for 2h, and vacuum drying at 70℃ for 4h to obtain (3-chloro-2-hydroxypropyl) octadecyl dimethyl ammonium chloride;
[0059] S2: 80 g of anhydrous ethanol, 22 g of (3-chloro-2-hydroxypropyl) octadecyl dimethyl ammonium chloride, and 18 g of 2-(dimethylamino) propionate dodecyl hydrochloride were added to the reactor in sequence, stirred and mixed at room temperature, and heated to reflux for 20 h. After the reaction was completed, the mixture was distilled at 60 ° C under reduced pressure for 2 h, and vacuum dried at 70 ° C for 4 h to obtain intermediate 1;
[0060] S3: Under nitrogen protection, 300 g toluene, 10 g allyl succinic anhydride, and 180 g intermediate 1 were added to the reactor in sequence, stirred and mixed, heated to 70°C, kept warm for 0.5 h, then heated to 80°C, and then 0.05 g catalyst tetraisopropyl titanate was added, kept warm for 10 min, and then heated to 100°C. The water generated during the reaction was removed by a water separator, reacted for 3 h, washed with 200 g deionized water after the reaction was completed, and then dried with 200 g anhydrous sodium sulfate for 2 h, distilled at 60°C under reduced pressure for 2 h, and vacuum dried at 70°C for 4 h to obtain intermediate 2;
[0061] S4: Under nitrogen protection, 60 g of tetrahydrofuran, 20 g of intermediate 2 and 0.036 g of azobisisobutyronitrile were added to the reaction container in sequence, stirred and mixed, heated to 60°C, and reacted for 14 h. After the reaction, 100 g of deionized water was added for washing, and then dried with 100 g of anhydrous sodium sulfate for 2 h, distilled under reduced pressure at 65°C for 2 h, and vacuum dried at 70°C for 4 h to obtain a modified surfactant with a number average molecular weight of 31850.
[0062] Example 4 Preparation of a cupping spray:
[0063] (1) Weigh the following raw materials by weight: 30 g of Angelica sinensis, 15 g of frankincense, 30 g of asarum, 10 g of saffron, 15 g of Corydalis yanhusuo, 12 g of Chuanxiong, 20 g of Buddleja buddleja, 10 g of Herba scutellariae, 5 g of Panax notoginseng, 20 g of Salvia miltiorrhizae, 14 g of Aconitum carmichaelii, 18 g of Millettia reticulatae, 15 g of Sanguisorba officinalis, 4 g of modified surfactant (prepared in Example 1), 8 g of absorption enhancer (laurocapram), and 300 g of deionized water;
[0064] (2) soaking the raw material weighed in step (1) in 3000 parts by weight of 60° kaoliang wine, and after 25 days, filtering and retaining the soaking liquid;
[0065] (3) placing the immersion liquid prepared in step (2) into a container and heating it to 60° C. for 8 minutes to obtain a medicinal solution;
[0066] (4) 500 g of the liquid medicine prepared in step (3), 50 g of red yeast rice, and 15 g of borneol were placed in a porcelain jar and fermented at room temperature for 20 days to obtain a cupping spray.
[0067] Example 5 Preparation of a cupping spray:
[0068] (1) Weigh the following raw materials by weight: 35 g of Angelica sinensis, 18 g of frankincense, 35 g of asarum, 15 g of saffron, 20 g of Corydalis yanhusuo, 16 g of Chuanxiong, 24 g of Buddleja buddleja, 14 g of Herba scutellariae, 10 g of Panax notoginseng, 25 g of Salvia miltiorrhizae, 18 g of Aconitum carmichaelii, 22 g of Millettia spatholobi, 24 g of Sanguisorba officinalis, 6 g of modified surfactant (prepared in Example 2), 10 g of absorption enhancer (laurocapram), and 300 g of deionized water;
[0069] (2) soaking the raw materials weighed in step (1) in 3000 parts by weight of 60° kaoliang wine, and after 28 days, filtering and retaining the soaking liquid;
[0070] (3) placing the immersion solution prepared in step (2) into a container and heating it to 70° C. for 4 min to obtain a medicinal solution;
[0071] (4) 600 g of the liquid medicine prepared in step (3), 60 g of red yeast rice, and 18 g of borneol were placed in a porcelain jar and fermented at room temperature for 25 days to obtain a cupping spray.
[0072] Example 6 Preparation of a cupping spray:
[0073] (1) Weigh the following raw materials by weight: 40 g of Angelica sinensis, 20 g of frankincense, 40 g of asarum, 20 g of saffron, 25 g of Corydalis yanhusuo, 18 g of Ligusticum chuanxiong, 26 g of Buddleja buddleja, 18 g of Herba scutellariae, 15 g of Notoginseng, 30 g of Salvia miltiorrhizae, 22 g of Radix Aconiti Kusnezoffii, 26 g of Millettia spatholobi, 30 g of Sanguisorba officinalis, 8 g of modified surfactant (prepared in Example 3), 12 g of absorption enhancer (laurocapram), and 300 g of deionized water;
[0074] (2) soaking the raw materials weighed in step (1) in 3000 parts by weight of 60° kaoliang wine, and after 30 days, filtering and retaining the infusion;
[0075] (3) placing the immersion liquid prepared in step (2) into a container and heating it to 80° C. for 2 min to obtain a medicinal solution;
[0076] (4) 700 g of the liquid medicine prepared in step (3), 70 g of red yeast rice, and 20 g of borneol were placed in a porcelain jar and fermented at room temperature for 30 days to obtain a cupping spray.
[0077] Comparative Example 1
[0078] A cupping spray, the raw material composition and process are basically the same as those of Example 5, the difference being that no modified surfactant is added to the composition.
[0079] Comparative Example 2
[0080] A cupping spray, the raw material composition and process are basically the same as those of Example 5, except that the modified surfactant is replaced by an equal weight of the intermediate 1 prepared in step S2 of Example 2.
[0081] Comparative Example 3
[0082] A cupping spray, the raw material composition and process are basically the same as those of Example 5, except that the modified surfactant is replaced by an equal weight of the intermediate 2 prepared in step S3 of Example 2.
[0083] Comparative Example 4
[0084] A cupping spray, the raw material composition and process are basically the same as those of Example 5, the difference being that the modified surfactant is replaced by an equal weight of octadecyltrimethylammonium chloride.
[0085] Comparative Example 5
[0086] A cupping spray, the raw material composition and process are basically the same as those of Example 5, the difference being that the modified surfactant is replaced with an equal weight of a modified surfactant prepared by the following method.
[0087] The modified surfactant in this comparative example was prepared by the following method:
[0088] S1: 50 g of anhydrous ethanol, 5.34 g of N,N-dimethyldodecyl tertiary amine, and 2 g of concentrated hydrochloric acid (12 mol / L) were added to the reactor in sequence, stirred and mixed at room temperature, and then 6.94 g of epichlorohydrin was added, and the temperature was raised to reflux for reaction for 2 h. After the reaction was completed, the mixture was distilled at 60 ° C under reduced pressure for 1 h, and vacuum dried at 50 ° C for 6 h to obtain compound (II-1);
[0089] S2: 50 g of anhydrous ethanol, 17.06 g of compound (II-1) and 15.51 g of dodecylpropyl dimethyl tertiary amine were added into the reactor in sequence, stirred and mixed at room temperature, and refluxed at elevated temperature for 24 h. After the reaction, the mixture was distilled at 60 °C under reduced pressure for 1 h, and vacuum dried at 50 °C for 6 h to obtain a modified surfactant.
[0090] Comparative Example 6
[0091] A cupping spray, the raw material composition and process are basically the same as those of Example 5, the difference being that the modified surfactant is replaced with an equal weight of a modified surfactant prepared by the following method.
[0092] The modified surfactant in this comparative example was prepared by the following method:
[0093] S1: 80g of anhydrous ethanol, 16g of N,N-dimethyloctylamine, and 3g of concentrated hydrochloric acid (12mol / L) were added to the reactor in sequence, stirred and mixed at room temperature, and then 14g of epichlorohydrin was added, and the temperature was raised to reflux for reaction for 3h. After the reaction was completed, the reaction was carried out by reduced pressure distillation at 60℃ for 1.5h, and vacuum drying at 60℃ for 5h to obtain N-(3-chloro-2-hydroxypropyl)-N,N-dimethyloctane-1-amine;
[0094] S2: 80 g of anhydrous ethanol, 20 g of N-(3-chloro-2-hydroxypropyl)-N,N-dimethyloctan-1-amine, and 17 g of 2-(dimethylamino) propionic acid dodecyl hydrochloride were added to the reactor in sequence, stirred and mixed at room temperature, and heated to reflux for 24 h. After the reaction was completed, the mixture was distilled at 60° C. under reduced pressure for 1.5 h, and dried under vacuum at 60° C. for 5 h to obtain intermediate 3;
[0095] S3: Under nitrogen protection, 300 g toluene, 10 g allyl succinic anhydride, and 175 g intermediate 3 were added to the reactor in sequence, stirred and mixed, heated to 65°C, kept warm for 1 h, then heated to 80°C, and then 0.04 g catalyst tetraisopropyl titanate was added, kept warm for 13 min, and then heated to 95°C. The water generated during the reaction was removed by a water separator, reacted for 4 h, washed with 200 g deionized water after the reaction was completed, and then dried with 200 g anhydrous sodium sulfate for 2 h, distilled at 60°C under reduced pressure for 1.5 h, and vacuum dried at 60°C for 5 h to obtain intermediate 4;
[0096] S4: Under nitrogen protection, 60 g of tetrahydrofuran, 18 g of intermediate 4 and 0.034 g of azobisisobutyronitrile were added to the reaction container in sequence, stirred and mixed, and the temperature was raised to 55°C for reaction for 16 h. After the reaction, 100 g of deionized water was added for washing, and then dried with 100 g of anhydrous sodium sulfate for 2 h, distilled under reduced pressure at 65°C for 1.5 h, and vacuum dried at 60°C for 5 h to obtain a modified surfactant.
[0097] Comparative Example 7
[0098] A cupping spray, the raw material composition and process are basically the same as those of Example 5, the difference being that the modified surfactant is replaced with an equal weight of a modified surfactant prepared by the following method.
[0099] The modified surfactant in this comparative example was prepared by the following method:
[0100] S1: 80g of anhydrous ethanol, 16g of tetradecyl dimethyl tertiary amine, and 3g of concentrated hydrochloric acid (12mol / L) were added to the reactor in sequence, stirred and mixed at room temperature, and then 14g of epichlorohydrin was added, and the temperature was raised to reflux for reaction for 3h. After the reaction was completed, the reaction was carried out by reduced pressure distillation at 60℃ for 1.5h, and vacuum drying at 60℃ for 5h to obtain N-(3-chloro-2-hydroxypropyl)-N,N-dimethyltetradecane-1-amine;
[0101] S2: 80 g of anhydrous ethanol, 20 g of N-(3-chloro-2-hydroxypropyl)-N,N-dimethyltetradecane-1-amine, and 17 g of 2-(dimethylamino) propionic acid dodecyl hydrochloride were added to the reactor in sequence, stirred and mixed at room temperature, and heated to reflux for reaction for 24 h. After the reaction was completed, the mixture was distilled at 60° C. under reduced pressure for 1.5 h, and dried under vacuum at 60° C. for 5 h to obtain intermediate 5;
[0102] S3: Under nitrogen protection, 300 g toluene, 10 g allyl succinic anhydride, and 175 g intermediate 5 were added to the reactor in sequence, stirred and mixed, heated to 65°C, kept warm for 1 h, then heated to 80°C, and then 0.04 g catalyst tetraisopropyl titanate was added, kept warm for 13 min, and then heated to 95°C. The water generated during the reaction was removed by a water separator, reacted for 4 h, washed with 200 g deionized water after the reaction was completed, and then dried with 200 g anhydrous sodium sulfate for 2 h, distilled at 60°C under reduced pressure for 1.5 h, and vacuum dried at 60°C for 5 h to obtain intermediate 6;
[0103] S4: Under nitrogen protection, 60 g of tetrahydrofuran, 18 g of intermediate 6 and 0.034 g of azobisisobutyronitrile were added to the reaction container in sequence, stirred and mixed, heated to 55°C, and reacted for 16 h. After the reaction, 100 g of deionized water was added for washing, and then dried with 100 g of anhydrous sodium sulfate for 2 h, distilled under reduced pressure at 65°C for 1.5 h, and vacuum dried at 60°C for 5 h to obtain a modified surfactant.
[0104] Comparative Example 8
[0105] A cupping spray, the raw material composition and process are basically the same as those of Example 5, the difference being that the modified surfactant is replaced with an equal weight of a modified surfactant prepared by the following method.
[0106] The modified surfactant in this comparative example was prepared by the following method:
[0107] S1: 80 g of anhydrous ethanol, 16 g of hexadecyl dimethyl tertiary amine, and 3 g of concentrated hydrochloric acid (12 mol / L) were added to the reactor in sequence, stirred and mixed at room temperature, and then 14 g of epichlorohydrin was added, and the temperature was raised to reflux for reaction for 3 h. After the reaction was completed, the mixture was distilled at 60 ° C under reduced pressure for 1.5 h, and vacuum dried at 60 ° C for 5 h to obtain compound (II-2);
[0108] S2: 80 g of anhydrous ethanol, 20 g of compound (II-2), and 17 g of dodecylpropyl dimethyl tertiary amine were added to the reactor in sequence, stirred and mixed at room temperature, and heated to reflux for 24 h. After the reaction, the mixture was distilled at 60 °C under reduced pressure for 1.5 h, and dried under vacuum at 60 °C for 5 h to obtain intermediate 7;
[0109] S3: Under nitrogen protection, 300 g toluene, 10 g allyl succinic anhydride, and 175 g intermediate 7 were added to the reactor in sequence, stirred and mixed, heated to 65°C, kept warm for 1 h, then heated to 80°C, and then 0.04 g catalyst tetraisopropyl titanate was added, kept warm for 13 min, and then heated to 95°C. The water generated during the reaction was removed by a water separator, reacted for 4 h, washed with 200 g deionized water after the reaction was completed, and then dried with 200 g anhydrous sodium sulfate for 2 h, distilled at 60°C under reduced pressure for 1.5 h, and vacuum dried at 60°C for 5 h to obtain intermediate 8;
[0110] S4: Under nitrogen protection, 60 g of tetrahydrofuran, 18 g of intermediate 8 and 0.034 g of azobisisobutyronitrile were added to the reaction container in sequence, stirred and mixed, heated to 55°C, and reacted for 16 h. After the reaction, 100 g of deionized water was added for washing, and then dried with 100 g of anhydrous sodium sulfate for 2 h, distilled under reduced pressure at 65°C for 1.5 h, and vacuum dried at 60°C for 5 h to obtain a modified surfactant.
[0111] The 60° kaoliang liquor used in Examples 4-6 and Comparative Examples 1-8 of the present application is a light-fragrance kaoliang liquor produced by Luzhou Meiming Liquor Co., Ltd.
[0112] The surface tension and clarity of the cupping sprays prepared in Examples 4-6 and Comparative Examples 1-8 were tested. The test results are shown in Table 1.
[0113] Surface tension test: The test was carried out in accordance with QB / T1323-91, and the experimental instrument was JYW-200A automatic interfacial tension meter (Chengde Jinhe Instrument Manufacturing Co., Ltd.).
[0114] Clarity test: Take the cupping spray prepared in Examples 4-6 and Comparative Examples 1-8, accurately measure 60 ml of each and place them in the corresponding clean, scaled 100 ml beakers, seal them with plastic wrap and place them at room temperature to let them stand naturally. When the samples are left standing for 30 days, 60 days and 120 days, place them at a location with an illumination of 2000-3000 lx (fluorescent lamp), carefully observe the sedimentation from the bottom of each beaker to the 20 ml scale, and make corresponding records. The test results are shown in Table 1.
[0115] Table 1
[0116]
[0117] It can be seen from Examples 4, 5 and 6 in Table 1 that the surface tension of the cupping spray prepared by the present invention is lower than 45.0 mN / m, and there is no sedimentation phenomenon in the clarity test, which has good stability, is convenient for long-term storage, and is beneficial to the efficacy.
[0118] Comparative Example 1 is a comparative example without adding modified surfactant. It can be seen from the data in Table 1 that its surface tension is 72.5 mN / m. A slight amount of sedimentation occurs after standing for 30 days, a small amount of sedimentation occurs after standing for 60 days, and a large amount of sedimentation occurs after standing for 120 days. The stability is very poor, it is very easy to settle, and it is not conducive to storage.
[0119] Comparative Example 2 is different from Example 5, and the difference is that the modified surfactant is replaced by an equal weight of the intermediate 1 prepared in step S2 of Example 2. It can be seen from the data in Table 1 that its surface tension is 57.3 mN / m, and a slight amount of sedimentation occurs after standing for 60 days, and a small amount of sedimentation occurs after standing for 120 days. The stability is relatively poor, which is not conducive to storage.
[0120] Comparative Example 3 is different from Example 5, and the difference is that the modified surfactant is replaced by an equal weight of the intermediate 2 prepared in step S3 of Example 2. It can be seen from the data in Table 1 that its surface tension is 53.2 mN / m, and a slight amount of sedimentation occurs after standing for 60 days, and a small amount of sedimentation occurs after standing for 120 days. The stability is relatively poor, which is not conducive to storage.
[0121] Comparative Example 4 is different from Example 5, and the difference is that the modified surfactant is replaced by an equal weight of octadecyltrimethylammonium chloride. It can be seen from the data in Table 1 that its surface tension is 59.4 mN / m, and a slight amount of sedimentation occurs after standing for 60 days, and a small amount of sedimentation occurs after standing for 120 days. The stability is relatively poor, which is not conducive to storage.
[0122] Comparative Example 5 is different from Example 5, and the difference is that the modified surfactant is replaced by the modified surfactant prepared by the method in Comparative Example 5. It can be seen from the data in Table 1 that its surface tension is 59.8 mN / m, and a slight amount of sedimentation occurs when it is left standing for 60 days, and a small amount of sedimentation occurs when it is left standing for 120 days. The stability is relatively poor, which is not conducive to storage.
[0123] Comparative Example 6 is different from Example 5, and the difference is that the modified surfactant is replaced by the modified surfactant prepared by the method in Comparative Example 6. It can be seen from the data in Table 1 that its surface tension is 49.6 mN / m, and a slight amount of sedimentation occurs when it is left standing for 120 days, so it can be stored for a short period of time.
[0124] Comparative Example 7 is different from Example 5, and the difference is that the modified surfactant is replaced by the modified surfactant prepared by the method in Comparative Example 7. It can be seen from the data in Table 1 that its surface tension is 48.2 mN / m, and a slight amount of sedimentation occurs when it is left standing for 120 days, so it can be stored for a short period of time.
[0125] Comparative Example 8 is different from Example 5, and the difference is that the modified surfactant is replaced by the modified surfactant prepared by the method in Comparative Example 8. It can be seen from the data in Table 1 that its surface tension is 46.1 mN / m, and a slight amount of sedimentation occurs when it is left standing for 120 days, so it can be stored for a short period of time.
[0126] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. However, any equivalent changes, modifications and evolutions made by ordinary technicians in the field without departing from the scope of the technical solution of the present invention by using the technical content disclosed above are all equivalent embodiments of the present invention. At the same time, any equivalent changes, modifications and evolutions made to the above embodiments based on the essential technology of the present invention are still within the protection scope of the technical solution of the present invention.
Claims
1. A cupping spray, characterized in that: The invention comprises the following raw materials in parts by weight: Angelica: 30-40 servings, Frankincense: 15-20 parts, Asarum: 30-40 servings, Saffron: 10-20 parts, Yuanhu: 15-25 parts, Chuanxiong: 12-18 parts, Buddleja buddha: 20-26 parts, Thunbergia truncatula: 10-18 parts, Panax notoginseng: 5-15 servings, Purple salvia: 20-30 portions, Processed Radix Aconiti Kusnezoffii: 14-22 servings, Millettia reticulata: 18-26 servings, Dragon's blood: 15-30 portions, Borneol: 15-20 parts, Modified surfactant: 4-8 parts, Absorption enhancer: 8-12 parts, Deionized water: 300 parts; The modified surfactant is prepared by the following method: S1: Anhydrous ethanol, octadecyl dimethyl tertiary amine and concentrated hydrochloric acid are added to the reactor in sequence, stirred and mixed at room temperature, and then epichlorohydrin is added, and the temperature is raised and refluxed for reaction for 2-4 hours to obtain (3-chloro-2-hydroxypropyl) octadecyl dimethyl ammonium chloride; S2: Anhydrous ethanol, (3-chloro-2-hydroxypropyl) octadecyl dimethyl ammonium chloride, and 2-(dimethylamino) dodecyl propionate hydrochloride are added to the reactor in sequence, stirred and mixed at room temperature, and heated to reflux for reaction for 20-28 hours to obtain intermediate 1; S3: Under nitrogen protection, toluene, allyl succinic anhydride and intermediate 1 are added to the reactor in sequence, stirred and mixed, heated to 60-70°C, kept warm for 0.5-1.5h, then heated to 80°C, and then tetraisopropyl titanate catalyst was added, kept warm for 10-15min, and then heated to 90-100°C, reacted for 3-5h, to obtain intermediate 2; S4: Under nitrogen protection, tetrahydrofuran, intermediate 2, and azobisisobutyronitrile are added to a reaction container in sequence, stirred and mixed, heated to 50-60° C., and reacted for 14-18 hours to obtain a modified surfactant.
2. A cupping spray according to claim 1, characterized in that: The number average molecular weight of the modified surfactant is 20,000-32,000.
3. The cupping spray according to claim 1, characterized in that: In step S1, the mass ratio of anhydrous ethanol, octadecyl dimethyl tertiary amine, epichlorohydrin and concentrated hydrochloric acid is 80:(12-18):(12-16):(2-4).
4. The cupping spray according to claim 1, characterized in that: In step S2, the mass ratio of anhydrous ethanol, (3-chloro-2-hydroxypropyl) octadecyl dimethyl ammonium chloride, and 2-(dimethylamino) dodecyl propionate hydrochloride is 80:(18-22):(16-18).
5. The cupping spray according to claim 1, characterized in that: In step S3, the mass ratio of toluene, allyl succinic anhydride, intermediate 1, and catalyst tetraisopropyl titanate is 300:10:(170-180):(0.03-0.05).
6. The cupping spray according to claim 1, characterized in that: In step S4, the mass ratio of tetrahydrofuran, intermediate 2 and azobisisobutyronitrile is 30:(8-10):(0.016-0.018).
7. The cupping spray according to claim 1, characterized in that: The absorption enhancer is laurocapram.
8. A method for preparing a cupping spray according to any one of claims 1 to 7, characterized in that: The following steps are involved: (1) Weigh the following raw materials by weight: 30-40 parts of Angelica sinensis, 15-20 parts of frankincense, 30-40 parts of asarum, 10-20 parts of saffron, 15-25 parts of Corydalis yanhusuo, 12-18 parts of Chuanxiong, 20-26 parts of Buddleja buddleja, 10-18 parts of Tilbury's lily, 5-15 parts of Panax notoginseng, 20-30 parts of Salvia miltiorrhiza, 14-22 parts of prepared Aconitum kusnezoffii, 18-26 parts of Millettia spatholobi, 15-30 parts of Sanguisorba officinalis, 4-8 parts of modified surfactant, 8-12 parts of absorption enhancer, and 300 parts of deionized water; (2) soaking the raw materials weighed in step (1) in 3000 parts by weight of 60° kaoliang wine, and after 25-30 days, filtering and retaining the soaking liquid; (3) placing the infusion prepared in step (2) into a container and heating it to 60-80° C. for 2-8 minutes to obtain a medicinal solution; (4) Add red yeast rice and 15-20 parts by weight of borneol to the medicinal solution prepared in step (3), wherein the weight ratio of the medicinal solution to red yeast rice is 10:1, and then ferment in a porcelain jar at room temperature for 20-30 days to obtain a cupping spray.
Citation Information
Patent Citations
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