Compound dendrobium officinale oral liquid and preparation method thereof
The active ingredients of Dendrobium officinale are extracted through ultrasonic water bath extraction and ethanol precipitation technology, and combined with the use of modified sodium alginate and other ingredients, it solves the stability and taste problems of the existing Dendrobium officinale oral liquid and achieves more efficient efficacy and Better market acceptance.
Patent Information
- Application Number
- CN202411605666.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-12
- Publication Date
- 2025-01-21
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
The existing Dendrobium officinale oral liquid has poor stability, antioxidant properties and taste, and the traditional preparation method has problems such as low extraction efficiency, easy destruction of active ingredients, and inconvenient storage and carrying.
Ultrasonic water bath is used to combine the method of ethanol precipitation to extract the active ingredients of Chinese herbal medicines, and to prepare sodium alginate through a specific chemical modification method, add sugarcane clear juice, rock sugar, wolfberry honey, and L-apple acid and other ingredients. Treatment to improve stability and taste.
Improve the efficacy, taste, safety, antioxidant activity and stability of Dendrobium oral solution, and enhance market acceptance and environmental friendship.
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Abstract
Description
Technical Field
[0001] The invention relates to the technical field of medicine, and in particular to a compound dendrobium officinale oral liquid and a preparation method thereof. Background Art
[0002] Dendrobium officinale, a herbaceous plant of the genus Dendrobium in the orchid family, is widely regarded as a medicinal material with high medicinal value in traditional Chinese medicine. Its dried stems are used to treat a variety of diseases, including but not limited to improving immunity, anti-inflammatory, anti-oxidation, promoting digestion and enhancing physical strength.
[0003] As the pace of modern life accelerates, people pay more and more attention to health and disease prevention, and the demand for efficient and convenient health care products is growing. As a new form of health care products, oral liquid is gradually becoming popular in the market for its characteristics of easy intake, rapid absorption and easy carrying.
[0004] Traditional methods of using Dendrobium officinale, such as decoction and tea making, are simple, but have problems such as low extraction efficiency, easy destruction of active ingredients, and inconvenient storage and carrying. In addition, traditional methods make it difficult to achieve efficient utilization and precise control of active ingredients in Dendrobium officinale. Dendrobium officinale products prepared by traditional methods are usually difficult to preserve, easily affected by moisture, deteriorate, and have a short shelf life.
[0005] China's invention patent CN109223986A discloses a compound oral liquid of Dendrobium officinale and its preparation method, including the following steps: S100, soaking the corresponding weight portions of Dendrobium officinale, Angelica sinensis, White Peony Root, Citron, Rose and Chrysanthemum in water for 0.5-3h, adding 8-12 times the amount of water and boiling for 2-3 times, each time for 1-2h, filtering out the drug residues, and obtaining an extract; S200, concentrating to 2.5-3.5 times the amount of the medicinal materials at 50-70°C, obtaining a concentrated solution; S300, standing at 4-25°C for more than 4h, filtering or centrifuging, adding flavoring agents and preservatives, stirring to dissolve, fixing the volume, filling, and sterilizing. Thus, the innovative formula, preparation and preparation process methods can help improve antioxidant properties and improve sleep, and improve cell viability. However, the stability, antioxidant properties and taste of the oral liquid of the invention are poor. Summary of the invention
[0006] In view of the limitations of the prior art, the present invention provides a Dendrobium officinale oral liquid that aims to improve efficacy, taste, safety, antioxidant activity and stability through innovative compound formulations and sophisticated preparation processes, while having better market acceptance and environmental friendliness.
[0007] In order to achieve the above-mentioned object of the invention, the present invention adopts the following technical solutions:
[0008] A preparation method of a compound Dendrobium officinale oral liquid is as follows:
[0009] Step 1, crushing the Chinese herbal medicine composition through an 80-mesh sieve, and then using water 15 to 25 times the weight of the Chinese herbal medicine composition as an extracting solution, extracting through an ultrasonic water bath, after the extraction is completed, filtering the filtrate and precipitating it 1 to 3 times with 3 to 5 times the volume of 40 to 80 wt% ethanol aqueous solution, and dissolving it with water 50 to 100 times the weight of the precipitate to obtain an extract;
[0010] Step 2: Mix the extract with the additive and modified sodium alginate, and sterilize the prepared oral liquid at high temperature to obtain the compound Dendrobium officinale oral liquid.
[0011] The Chinese herbal medicine composition is composed of the following materials in parts by weight: 15 to 20 parts of dendrobium officinale, 5 to 10 parts of vitex rotundifolia, 10 to 15 parts of forsythia suspensa, 3 to 5 parts of momordica grosvenori and 1 to 3 parts of liquorice.
[0012] The parameters of the ultrasonic water bath extraction are extraction at 50-60° C. for 1-3 hours, an ultrasonic frequency of 40-80 kHz, and a power of 100-300W.
[0013] The additive is composed of the following materials in parts by weight: 25-35 parts of sugarcane juice, 0.5-2 parts of crystal sugar, 0.5-2 parts of wolfberry honey, and 0.02-0.04 parts of L-malic acid.
[0014] The weight ratio of the extract to the additive is 1000:20-40.
[0015] The weight ratio of the extract to the modified sodium alginate is 1000:0.3-0.5.
[0016] The high temperature sterilization treatment is a high temperature sterilization treatment at 90 to 110° C. for 5 to 15 minutes.
[0017] The preparation method of the modified sodium alginate is as follows, in parts by weight:
[0018] S1. Add 1 to 3 parts of sodium alginate to 80 to 120 parts of water, and heat at 50 to 70°C until completely dissolved to form a sodium alginate solution; add 0.6 to 1 part of N-hydroxy-5-norbornene-2,3-dicarboximide and 0.6 to 1 part of dimethylaminopropylethylcarbamide to 40 to 60 parts of water to obtain an activated solution; add the activated solution to the sodium alginate solution, and keep stirring for 3 to 8 hours to obtain an activated mixture;
[0019] S2, adding 0.8-1.2 parts of levodopa to the activated mixture prepared in step S1, and adjusting the pH to 4.5-6.5 with 0.5-2 mol / L hydrochloric acid, treating for 8-12 hours, and terminating the reaction with 0.5-2 wt% sodium hydroxide aqueous solution, placing the reaction mixture in a dialysis bag, and dialyzing with water, the molecular weight cutoff of the dialysis bag is 3500-10000, after dialysis, washing the product with water 1-3 times, and freeze-drying at -40--80°C to obtain modified sodium alginate.
[0020] Further preferably, the preparation method of the modified sodium alginate is as follows, in parts by weight:
[0021] S1. Add 1 to 3 parts of sodium alginate to 80 to 120 parts of water, and heat at 50 to 70°C until completely dissolved to form a sodium alginate solution; add 0.6 to 1 part of N-hydroxy-5-norbornene-2,3-dicarboximide and 0.6 to 1 part of dimethylaminopropylethylcarbamide to 40 to 60 parts of water to obtain an activated solution; add the activated solution to the sodium alginate solution, and keep stirring for 3 to 8 hours to obtain an activated mixture;
[0022] S2. Add 0.4-0.6 parts of levodopa and 0.4-0.6 parts of 1,8-octanediamine to the activated mixture prepared in step S1, and adjust the pH to 4.5-6.5 with 0.5-2 mol / L hydrochloric acid, treat for 8-12 hours, terminate the reaction with 0.5-2 wt % sodium hydroxide aqueous solution, place the reaction mixture in a dialysis bag, and dialyze with water, the molecular weight cutoff of the dialysis bag is 3500-10000, after dialysis, wash the product with water 1-3 times, and freeze-dry at -40 to -80°C to obtain modified sodium alginate.
[0023] The compound Dendrobium officinale health-care oral liquid prepared by the invention has the effects of promoting body fluid and quenching thirst, clearing away heat and detoxifying, moistening the lungs and relieving cough, benefiting the throat and stomach, and promoting diuresis and reducing inflammation, and can also enhance the body's immunity, lower blood sugar and blood pressure, prevent hyperlipidemia, resist cataracts, have antioxidant effects, and resist tumors.
[0024] In the preparation method of the compound Dendrobium officinale health oral liquid, the functions of each substance are as follows:
[0025] Dendrobium officinale provides major active ingredients, such as polysaccharides, which have immunomodulatory, anti-inflammatory, and antioxidant effects.
[0026] Chinese herbal ingredients such as Vitex rotundifolia, Forsythia suspensa, Momordica grosvenori and Licorice usually have their own pharmacological effects, such as anti-inflammatory, antitussive, heat-clearing and detoxifying, etc., and work synergistically with Dendrobium officinale to enhance the overall effect of the health oral liquid.
[0027] Water is used as an extracting liquid to extract the active ingredients in medicinal materials.
[0028] Ultrasonic waves create mechanical vibrations in a water bath, helping to break up plant cell walls and making it easier for active ingredients to be released into the extract.
[0029] Ethanol is used as a precipitant to precipitate proteins and other high-molecular impurities in the extract, and the effective ingredients are purified through multiple precipitations.
[0030] Sugarcane juice, rock sugar, and wolfberry honey provide sweetness and energy, while wolfberry honey may contribute additional health-promoting ingredients.
[0031] L-Malic acid acts as a flavoring agent to enhance the flavor of the oral solution and may provide a slight antioxidant effect.
[0032] Sodium alginate acts as a stabilizer and thickener to improve the physical properties of oral solutions, such as stability.
[0033] N-hydroxy-5-norbornene-2,3-dicarboximide is used as an activator to react with sodium alginate to increase its reactivity and prepare for the subsequent modification steps.
[0034] Dimethylaminopropylethylcarbamide may act as an intermediate and participate in the modification process of sodium alginate.
[0035] In the preparation of modified sodium alginate, levodopa may act as a compound that reacts with activated sodium alginate to change the properties of sodium alginate.
[0036] Sodium hydroxide is used to terminate the reaction and neutralize excess activator.
[0037] Use dialysis bags for molecular weight cutoff to remove unreacted starting materials and by-products.
[0038] Freeze drying is used to remove water from the dialyzed solution to obtain solid modified sodium alginate.
[0039] Through the combined effects of these ingredients and steps, the prepared compound Dendrobium officinale health oral liquid aims to provide health functions such as immune regulation and anti-oxidation, while having good taste and stability.
[0040] Compared with the prior art, it has the following beneficial effects:
[0041] 1) The compound Dendrobium officinale health oral liquid of the present invention may enhance the immune regulation, anti-inflammatory, antioxidant and other effects of the health oral liquid by combining Dendrobium officinale with other Chinese medicinal materials (such as Vitex rotundifolia, Forsythia suspensa, Momordica grosvenori and Licorice).
[0042] 2.) The ultrasonic-assisted water bath extraction method of the compound Dendrobium officinale health oral liquid of the present invention may improve the extraction efficiency of the active ingredients and ensure the full extraction of the active ingredients. The ethanol precipitation method may effectively remove the protein and other impurities in the extract and improve the purity of the final product.
[0043] 3) The sodium alginate prepared by a specific chemical modification method in the compound Dendrobium officinale health-care oral liquid of the present invention may enhance the stability, antioxidant properties and biocompatibility of the oral liquid.
[0044] 4) The compound Dendrobium officinale health oral liquid of the present invention is added with ingredients such as sugarcane juice, crystal sugar, wolfberry honey and L-malic acid, which may improve the taste of the oral liquid and make it more acceptable to consumers. DETAILED DESCRIPTION
[0045] Main sources of substances:
[0046] Dendrobium officinale: Origin: Huoshan County, Anhui Province.
[0047] Vitex rotundifolia: Originated from Heze, Shandong.
[0048] Forsythia: Origin: Handan, Hebei.
[0049] Monk Fruit: Originated from Yongfu County, Guangxi.
[0050] Licorice: Originated from Ordos, Inner Mongolia.
[0051] Sugarcane juice: Xi'an Heshun Biotechnology Co., Ltd., product grade: food grade.
[0052] Rock sugar: Zhangzhou Shanfeng Food Co., Ltd., item number: SFHBT-006.
[0053] Wolfberry honey: Chengdu Chongxin Biotechnology Co., Ltd., product number: Bulk wolfberry honey 75kg.
[0054] L-Malic acid: Guangzhou Huafa Food Raw Materials Co., Ltd., product number: 003.
[0055] The preparation method of the compound Dendrobium officinale health-care oral liquid of the present invention involves multiple steps, each of which has its specific function:
[0056] The medicinal materials were crushed and passed through an 80-mesh sieve to increase the contact area between the medicinal materials and water, which is beneficial to the extraction of the components. 20 times the weight of water was used as the extracting liquid, and ultrasonic-assisted (55°C, 60kHz, 200W) water bath extraction was performed for 2 hours, using the mechanical and thermal effects of ultrasound to accelerate the dissolution and release of the components.
[0057] The extracted medicinal materials are filtered to obtain a filtrate containing active ingredients. The filtrate is precipitated three times with a 50wt% ethanol aqueous solution to remove impurities insoluble in ethanol and improve the purity of the extract. The precipitate is dissolved with water 80 times the weight of the precipitate to obtain an extract containing active ingredients of medicinal materials such as Dendrobium candidum.
[0058] The extract is mixed with sugarcane juice, rock sugar, wolfberry honey, L-malic acid and modified sodium alginate to adjust the taste and stability of the oral solution.
[0059] High temperature sterilization at 100°C for 8 minutes ensures that the oral solution meets commercial sterility standards and extends the shelf life.
[0060] Sodium alginate is added to water and heated to dissolve to form a uniform sodium alginate solution. An activation solution is formed by adding N-hydroxy-5-norbornene-2,3-dicarboximide and dimethylaminopropylethylcarbamide to increase the activity of sodium alginate. After activation, levodopa is added to react to form modified sodium alginate. The reaction is terminated with an aqueous sodium hydroxide solution to prevent overreaction. The reaction mixture is placed in a dialysis bag and dialyzed with deionized water to remove unreacted raw materials and by-products. After dialysis, the solid product is washed with water to remove residual impurities, and then freeze-dried to obtain modified sodium alginate.
[0061] These steps work together to prepare a compound Dendrobium officinale health oral liquid that contains active ingredients of traditional Chinese medicinal materials and has good taste and stability.
[0062] Example 1
[0063] A preparation method of a compound Dendrobium officinale oral liquid is as follows:
[0064] Step 1, 18g of Dendrobium candidum, 8g of Vitex rotundus, 12g of Forsythia suspensa, 4g of Momordica grosvenori and 2g of Licorice are crushed and passed through an 80-mesh sieve, and then 20 times the weight of water of the Chinese herbal medicine composition is used as an extracting solution, and ultrasonic extraction is performed in a 55°C water bath for 2 hours, with an ultrasonic frequency of 60kHz and a power of 200W. After the extraction, the filtrate obtained by filtration is precipitated 3 times with 4 times the volume of 50wt% ethanol aqueous solution, and dissolved with water 80 times the weight of the precipitate to obtain an extract;
[0065] Step 2: Mix 1000 g of the extract with 30 g of sugarcane juice, 1 g of crystal sugar, 1 g of wolfberry honey, 0.03 g of L-malic acid, and 0.4 g of modified sodium alginate, and sterilize the prepared oral solution at 100° C. for 8 min to obtain the compound Dendrobium officinale oral solution.
[0066] The preparation method of the modified sodium alginate is as follows:
[0067] S1. Add 2 g of sodium alginate to 100 g of water, and heat at 60° C. until completely dissolved to form a sodium alginate solution; add 0.8 g of N-hydroxy-5-norbornene-2,3-dicarboximide and 0.8 g of dimethylaminopropylethylcarbamide to 50 g of water to obtain an activated solution; add the activated solution to the sodium alginate solution, and keep stirring for 5 hours to obtain an activated mixture;
[0068] S2. Add 1 g of levodopa to the activated mixture prepared in step S1, and adjust the pH to 5 with 1 mol / L hydrochloric acid, treat for 10 hours, terminate the reaction with 1 wt% sodium hydroxide aqueous solution, place the reaction mixture in a dialysis bag, and dialyze with water. The molecular weight cutoff of the dialysis bag is 5000. After dialysis, wash the product with water 3 times, and freeze-dry at -60°C to obtain modified sodium alginate.
[0069] Example 2
[0070] The preparation method of a compound Dendrobium officinale oral liquid is basically the same as that of Example 1, except that the preparation method of the modified sodium alginate is different:
[0071] The preparation method of the modified sodium alginate is as follows:
[0072] S1. Add 2 g of sodium alginate to 100 g of water, and heat at 60° C. until completely dissolved to form a sodium alginate solution; add 0.8 g of N-hydroxysulfonic acid succinimide and 0.8 g of dimethylaminopropyl ethylcarbamide to 50 g of water to obtain an activated solution; add the activated solution to the sodium alginate solution, and keep stirring for 5 hours to obtain an activated mixture;
[0073] S2. Add 1 g of levodopa to the activated mixture prepared in step S1, and adjust the pH to 5 with 1 mol / L hydrochloric acid, treat for 10 hours, terminate the reaction with 1 wt% sodium hydroxide aqueous solution, place the reaction mixture in a dialysis bag, and dialyze with water. The molecular weight cutoff of the dialysis bag is 5000. After dialysis, wash the product with water 3 times, and freeze-dry at -60°C to obtain modified sodium alginate.
[0074] Example 3
[0075] The preparation method of a compound Dendrobium officinale oral liquid is basically the same as that of Example 1, except that the preparation method of the modified sodium alginate is different:
[0076] The preparation method of the modified sodium alginate is as follows:
[0077] S1. Add 2 g of sodium alginate to 100 g of water, and heat at 60° C. until completely dissolved to form a sodium alginate solution; add 0.8 g of N-hydroxysuccinimide and 0.8 g of dimethylaminopropylethylcarbamide to 50 g of water to obtain an activated solution; add the activated solution to the sodium alginate solution, and keep stirring for 5 hours to obtain an activated mixture;
[0078] S2. Add 1 g of levodopa to the activated mixture prepared in step S1, and adjust the pH to 5 with 1 mol / L hydrochloric acid, treat for 10 hours, terminate the reaction with 1 wt% sodium hydroxide aqueous solution, place the reaction mixture in a dialysis bag, and dialyze with water. The molecular weight cutoff of the dialysis bag is 5000. After dialysis, wash the product with water 3 times, and freeze-dry at -60°C to obtain modified sodium alginate.
[0079] Example 4
[0080] The preparation method of a compound Dendrobium officinale oral liquid is basically the same as that of Example 1, except that the preparation method of the modified sodium alginate is different:
[0081] The preparation method of the modified sodium alginate is as follows:
[0082] S1. Add 2 g of sodium alginate to 100 g of water, and heat at 60° C. until completely dissolved to form a sodium alginate solution; add 0.8 g of N-hydroxy-5-norbornene-2,3-dicarboximide and 0.8 g of 1-(3-dimethylaminopropyl)-3-cyclohexylcarbodiimide to 50 g of water to obtain an activated solution; add the activated solution to the sodium alginate solution, and keep stirring for 5 hours to obtain an activated mixture;
[0083] S2. Add 1 g of levodopa to the activated mixture prepared in step S1, and adjust the pH to 5 with 1 mol / L hydrochloric acid, treat for 10 hours, terminate the reaction with 1 wt% sodium hydroxide aqueous solution, place the reaction mixture in a dialysis bag, and dialyze with water. The molecular weight cutoff of the dialysis bag is 5000. After dialysis, wash the product with water 3 times, and freeze-dry at -60°C to obtain modified sodium alginate.
[0084] Example 5
[0085] The preparation method of a compound Dendrobium officinale oral liquid is basically the same as that of Example 1, except that the preparation method of the modified sodium alginate is different:
[0086] The preparation method of the modified sodium alginate is as follows:
[0087] S1. Add 2 g of sodium alginate to 100 g of water, and heat at 60° C. until completely dissolved to form a sodium alginate solution; add 0.8 g of N-hydroxy-5-norbornene-2,3-dicarboximide and 0.8 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide to 50 g of water to obtain an activated solution; add the activated solution to the sodium alginate solution, and keep stirring for 5 hours to obtain an activated mixture;
[0088] S2. Add 1 g of levodopa to the activated mixture prepared in step S1, and adjust the pH to 5 with 1 mol / L hydrochloric acid, treat for 10 hours, terminate the reaction with 1 wt% sodium hydroxide aqueous solution, place the reaction mixture in a dialysis bag, and dialyze with water. The molecular weight cutoff of the dialysis bag is 5000. After dialysis, wash the product with water 3 times, and freeze-dry at -60°C to obtain modified sodium alginate.
[0089] Example 6
[0090] The preparation method of a compound Dendrobium officinale oral liquid is basically the same as that of Example 1, except that the preparation method of the modified sodium alginate is different:
[0091] The preparation method of the modified sodium alginate is as follows:
[0092] S1. Add 2 g of sodium alginate to 100 g of water, and heat at 60° C. until completely dissolved to form a sodium alginate solution; add 0.8 g of N-hydroxy-5-norbornene-2,3-dicarboximide and 0.8 g of dimethylaminopropylethylcarbamide to 50 g of water to obtain an activated solution; add the activated solution to the sodium alginate solution, and keep stirring for 5 hours to obtain an activated mixture;
[0093] S2. Add 1 g of 1,8-octanediamine to the activated mixture prepared in step S1, and adjust the pH to 5 with 1 mol / L hydrochloric acid, treat for 10 hours, terminate the reaction with 1 wt% sodium hydroxide aqueous solution, place the reaction mixture in a dialysis bag, and dialyze with water, the molecular weight cutoff of the dialysis bag is 5000, after dialysis, wash the product with water 3 times, and freeze-dry at -60°C to obtain modified sodium alginate.
[0094] Example 7
[0095] The preparation method of a compound Dendrobium officinale oral liquid is basically the same as that of Example 1, except that the preparation method of the modified sodium alginate is different:
[0096] The preparation method of the modified sodium alginate is as follows:
[0097] S1. Add 2 g of sodium alginate to 100 g of water, and heat at 60° C. until completely dissolved to form a sodium alginate solution; add 0.8 g of N-hydroxy-5-norbornene-2,3-dicarboximide and 0.8 g of dimethylaminopropylethylcarbamide to 50 g of water to obtain an activated solution; add the activated solution to the sodium alginate solution, and keep stirring for 5 hours to obtain an activated mixture;
[0098] S2. Add 1 g of octylamine to the activated mixture prepared in step S1, and adjust the pH to 5 with 1 mol / L hydrochloric acid, treat for 10 hours, terminate the reaction with 1 wt% sodium hydroxide aqueous solution, place the reaction mixture in a dialysis bag, and dialyze with water. The molecular weight cutoff of the dialysis bag is 5000. After dialysis, wash the product with water 3 times, and freeze-dry at -60°C to obtain modified sodium alginate.
[0099] Example 8
[0100] The preparation method of a compound Dendrobium officinale oral liquid is basically the same as that of Example 1, except that the preparation method of the modified sodium alginate is different:
[0101] The preparation method of the modified sodium alginate is as follows:
[0102] S1. Add 2 g of sodium alginate to 100 g of water, and heat at 60° C. until completely dissolved to form a sodium alginate solution; add 0.8 g of N-hydroxy-5-norbornene-2,3-dicarboximide and 0.8 g of dimethylaminopropylethylcarbamide to 50 g of water to obtain an activated solution; add the activated solution to the sodium alginate solution, and keep stirring for 5 hours to obtain an activated mixture;
[0103] S2. Add 1 g of dopamine to the activated mixture prepared in step S1, and adjust the pH to 5 with 1 mol / L hydrochloric acid, treat for 10 hours, terminate the reaction with 1 wt% sodium hydroxide aqueous solution, place the reaction mixture in a dialysis bag, and dialyze with water. The molecular weight cutoff of the dialysis bag is 5000. After dialysis, wash the product with water 3 times, and freeze-dry at -60°C to obtain modified sodium alginate.
[0104] Example 9
[0105] The preparation method of a compound Dendrobium officinale oral liquid is basically the same as that of Example 1, except that the preparation method of the modified sodium alginate is different:
[0106] The preparation method of the modified sodium alginate is as follows:
[0107] S1. Add 2 g of sodium alginate to 100 g of water, and heat at 60° C. until completely dissolved to form a sodium alginate solution; add 0.8 g of N-hydroxy-5-norbornene-2,3-dicarboximide and 0.8 g of dimethylaminopropylethylcarbamide to 50 g of water to obtain an activated solution; add the activated solution to the sodium alginate solution, and keep stirring for 5 hours to obtain an activated mixture;
[0108] S2. Add 0.5 g of 1,8-octanediamine and 0.5 g of levodopa to the activated mixture prepared in step S1, and adjust the pH to 5 with 1 mol / L hydrochloric acid. Treat for 10 h, terminate the reaction with 1 wt % aqueous sodium hydroxide solution, place the reaction mixture in a dialysis bag, and dialyze with water. The molecular weight cutoff of the dialysis bag is 5000. After dialysis, wash the product with water 3 times, and freeze-dry at -60°C to obtain modified sodium alginate.
[0109] Comparative Example 1
[0110] A preparation method of a compound Dendrobium officinale oral liquid is as follows:
[0111] Step 1, 18g of Dendrobium candidum, 8g of Vitex rotundus, 12g of Forsythia suspensa, 4g of Momordica grosvenori and 2g of Licorice are crushed and passed through an 80-mesh sieve, and then 20 times the weight of water of the Chinese herbal medicine composition is used as an extracting solution, and ultrasonic extraction is performed in a 55°C water bath for 2 hours, with an ultrasonic frequency of 60kHz and a power of 200W. After the extraction, the filtrate obtained by filtration is precipitated 3 times with 4 times the volume of 50wt% ethanol aqueous solution, and dissolved with water 80 times the weight of the precipitate to obtain an extract;
[0112] Step 2: Mix 1000 g of the extract with 30 g of sugarcane juice, 1 g of crystal sugar, 1 g of wolfberry honey, 0.03 g of L-malic acid, and 0.4 g of sodium alginate, and sterilize the prepared oral solution at 100° C. for 8 min to obtain the compound Dendrobium officinale oral solution.
[0113] Comparative Example 2
[0114] A preparation method of a compound Dendrobium officinale oral liquid is as follows:
[0115] Step 1, 18g of Dendrobium candidum, 8g of Vitex rotundus, 12g of Forsythia suspensa, 4g of Momordica grosvenori and 2g of Licorice are crushed and passed through an 80-mesh sieve, and then 20 times the weight of water of the Chinese herbal medicine composition is used as an extracting solution, and ultrasonic extraction is performed in a 55°C water bath for 2 hours, with an ultrasonic frequency of 60kHz and a power of 200W. After the extraction, the filtrate obtained by filtration is precipitated 3 times with 4 times the volume of 50wt% ethanol aqueous solution, and dissolved with water 80 times the weight of the precipitate to obtain an extract;
[0116] Step 2: Mix 1000 g of the extract with 30 g of sugarcane juice, 1 g of crystal sugar, 1 g of wolfberry honey, and 0.03 g of L-malic acid, and sterilize the prepared oral liquid at 100° C. for 8 min to obtain the compound Dendrobium officinale oral liquid.
[0117] Test Example 1
[0118] Stability test
[0119] The main functional substances of Dendrobium candidum are the polysaccharides it contains, which mainly include mannose and glucose. Modern pharmacological studies have found that these polysaccharides show outstanding biological activities in immune regulation, anti-inflammation, and hypoglycemic effects. The polysaccharide content in Dendrobium candidum is usually between 34% and 43%, which is one of its main medicinal ingredients.
[0120] In order to evaluate the stability of the mannose content in the compound Dendrobium officinale health oral liquid, this experiment used high performance liquid chromatography (HPLC) technology for quantitative analysis. The experimental process is as follows: The oral liquid samples to be analyzed were stored under environmental conditions of 45°C for 3 months. The initial content of mannose in the sample was recorded at the beginning of the experiment (i.e., 0 months). At the end of the experiment (i.e., 3 months), the sample was collected again and its mannose content was determined.
[0121] Taking the absolute content in October as the benchmark, divide the absolute value content in March by the absolute content in October to get the relative percentage content (%) in March.
[0122] The relative percentage content obtained was used as an indicator to measure the stability of the compound Dendrobium officinale health oral liquid within 3 months. The test results are shown in Table 1.
[0123] Table 1
[0124]
[0125]
[0126] Test Example 2
[0127] Antioxidant Test
[0128] The DPPH free radical scavenging test is a method for evaluating antioxidant capacity. The test is based on the characteristics of DPPH free radicals that appear purple in methanol solvent and have significant absorption at specific wavelengths. Antioxidants react with DPPH free radicals by donating electrons, resulting in color fading, and the degree of fading is proportional to the free radical scavenging efficiency.
[0129] Prepare 0.1 mmol / L DPPH methanol solution and 0.05 mmol / L Tris-HCl buffer solution. Mix 2 ml of DPPH methanol solution, 0.9 ml of Tris-HCl buffer solution and 0.5 ml of the oral solution to be tested as a sample tube. Mix 2 ml of DPPH methanol solution, 0.9 ml of Tris-HCl buffer solution and 0.5 ml of methanol as a control tube. Use distilled water to adjust the spectrophotometer to zero. Place the mixed sample in a dark environment for 30 minutes. Measure its absorbance at a wavelength of 517 nm.
[0130] Calculation formula: Clearance rate (%) = (absorbance of control tube - absorbance of sample tube) / absorbance of control tube) × 100.
[0131] The higher the free radical scavenging rate, the stronger its antioxidant property.
[0132] The test results are shown in Table 2.
[0133] Table 2
[0134]
[0135]
[0136] It can be seen from test examples 1 to 2 that the oral liquid obtained in the embodiment of the present invention has good stability and antioxidant properties.
[0137] N-hydroxy-5-norbornene-2,3-dicarboximide used in Example 1, N-hydroxysulfonic acid succinimide used in Example 2, and N-hydroxysuccinimide used in Example 3. Among them, N-hydroxy-5-norbornene-2,3-dicarboximide has a norbornene ring, and this ring structure may increase the stability of the molecule, and due to the N-hydroxyl group, it may promote the reactivity with the carboxyl group of sodium alginate. In contrast, although N-hydroxysulfonic acid succinimide and N-hydroxysuccinimide also have N-hydroxyl groups, the sulfonic acid group and the succinimide group may affect the nucleophilicity of the molecule, thereby affecting its reaction rate and efficiency with sodium alginate. The stereochemistry of N-hydroxy-5-norbornene-2,3-dicarboximide may help it form a more stable derivative with sodium alginate. The presence of the norbornene ring may provide a specific configuration for the molecule, which may help to form a helical structure or other structures that are conducive to improving performance during the modification process of sodium alginate. Compared with the other two compounds, N-hydroxy-5-norbornene-2,3-dicarboximide may be more structurally favorable to form stable derivatives with sodium alginate, and may provide better performance due to its unique stereochemistry and reactivity.
[0138] Comparison between Examples 1, 4 and 5 shows that the three compounds, dimethylaminopropyl ethyl carboxamide, 1-(3-dimethylaminopropyl)-3-cyclohexylcarbodiimide and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, all contain carbodiimide functional groups, which are their key active groups as activators. However, their alkyl chain lengths and structures are different, which may affect their reactivity with sodium alginate and the solubility and biocompatibility of the final product. Carbodiimide compounds react with the carboxyl group of sodium alginate to form more active carboxyl intermediates, which then react with compounds such as levodopa to form modified sodium alginate. Dimethylaminopropyl ethyl carboxamide may be more accessible to the carboxyl group of sodium alginate due to its shorter alkyl chain, thereby increasing the reaction rate. 1-(3-dimethylaminopropyl)-3-cyclohexylcarbodiimide and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide have cyclic structures and long alkyl chains, which may limit their reaction efficiency with the carboxyl groups of sodium alginate because steric hindrance may hinder the occurrence of effective collision and reaction.
[0139] L-DOPA, 1,8-octanediamine, octylamine, and dopamine are all compounds containing amine groups (-NH2), but they have different side chain structures and lengths. L-DOPA contains an aromatic ring and a carboxyl group, while 1,8-octanediamine, octylamine, and dopamine are aliphatic amines with different carbon chain lengths and branches. The amine group is a nucleophilic site that can react with activated carboxyl groups. Different amine compounds may have different nucleophilicities due to their different molecular structures, which affects their reaction rate and efficiency with activated carboxyl groups. 1,8-octanediamine may provide more flexibility in space because its two amine groups are connected by a longer carbon chain, making it easier to react with multiple activated carboxyl groups to form multiple covalent bonds.
[0140] In Example 9, the combination of levodopa and 1,8-octanediamine may produce a synergistic effect. The aromatic ring of levodopa may interact non-covalently with certain parts of sodium alginate through π-π stacking, increasing its local concentration on the sodium alginate chain, thereby increasing the probability of reaction with carboxyl groups. At the same time, the long chain of 1,8-octanediamine may enable it to form covalent bonds with more carboxyl groups, increasing the molecular weight and stability of the modified sodium alginate. The combination of levodopa and 1,8-octanediamine may improve the performance of modified sodium alginate due to their molecular structure characteristics and synergistic effects, thereby performing better in terms of stability and antioxidant properties.
Claims
1. A method for preparing a compound Dendrobium officinale oral liquid, characterized in that: Here’s how: Step 1, crushing the Chinese herbal medicine composition through an 80-mesh sieve, and then using water 15 to 25 times the weight of the Chinese herbal medicine composition as an extracting solution, extracting through an ultrasonic water bath, after the extraction is completed, filtering the filtrate and precipitating it 1 to 3 times with 3 to 5 times the volume of 40 to 80 wt% ethanol aqueous solution, and dissolving it with water 50 to 100 times the weight of the precipitate to obtain an extract; Step 2: Mix the extract with the additive and modified sodium alginate, and sterilize the prepared oral liquid at high temperature to obtain the compound Dendrobium officinale oral liquid.
2. The method for preparing the compound Dendrobium officinale oral liquid as claimed in claim 1, characterized in that: The Chinese herbal medicine composition is composed of the following materials in parts by weight: 15 to 20 parts of dendrobium officinale, 5 to 10 parts of vitex rotundifolia, 10 to 15 parts of forsythia suspensa, 3 to 5 parts of momordica grosvenori and 1 to 3 parts of liquorice.
3. The method for preparing the compound Dendrobium officinale oral liquid as claimed in claim 1, characterized in that: The parameters of the ultrasonic water bath extraction are extraction at 50-60° C. for 1-3 hours, an ultrasonic frequency of 40-80 kHz, and a power of 100-300W.
4. The method for preparing the compound Dendrobium officinale oral liquid as claimed in claim 1, characterized in that: The additive is composed of the following materials in parts by weight: 25-35 parts of sugarcane juice, 0.5-2 parts of crystal sugar, 0.5-2 parts of wolfberry honey, and 0.02-0.04 parts of L-malic acid.
5. The method for preparing the compound Dendrobium officinale oral liquid as claimed in claim 1, characterized in that: The weight ratio of the extract to the additive is 1000:20-40.
6. The method for preparing the compound Dendrobium officinale oral liquid as claimed in claim 1, characterized in that: The weight ratio of the extract to the modified sodium alginate is 1000:0.3-0.
5.
7. The method for preparing the compound Dendrobium officinale oral liquid as claimed in claim 1, characterized in that: The high temperature sterilization treatment is a high temperature sterilization treatment at 90 to 110° C. for 5 to 15 minutes.
8. The method for preparing the compound Dendrobium officinale oral liquid as claimed in claim 1, characterized in that: The preparation method of the modified sodium alginate is as follows, in parts by weight: S1. Add 1 to 3 parts of sodium alginate to 80 to 120 parts of water, and heat at 50 to 70°C until completely dissolved to form a sodium alginate solution; add 0.6 to 1 part of N-hydroxy-5-norbornene-2,3-dicarboximide and 0.6 to 1 part of dimethylaminopropylethylcarbamide to 40 to 60 parts of water to obtain an activated solution; add the activated solution to the sodium alginate solution, and keep stirring for 3 to 8 hours to obtain an activated mixture; S2, adding 0.8-1.2 parts of levodopa to the activated mixture prepared in step S1, and adjusting the pH to 4.5-6.5 with 0.5-2 mol / L hydrochloric acid, treating for 8-12 hours, and terminating the reaction with 0.5-2 wt% sodium hydroxide aqueous solution, placing the reaction mixture in a dialysis bag, and dialyzing with water, the molecular weight cutoff of the dialysis bag is 3500-10000, after dialysis, washing the product with water 1-3 times, and freeze-drying at -40--80°C to obtain modified sodium alginate.
9. The method for preparing the compound Dendrobium officinale oral liquid as claimed in claim 1, characterized in that: The preparation method of the modified sodium alginate is as follows, in parts by weight: S1. Add 1 to 3 parts of sodium alginate to 80 to 120 parts of water, and heat at 50 to 70°C until completely dissolved to form a sodium alginate solution; add 0.6 to 1 part of N-hydroxy-5-norbornene-2,3-dicarboximide and 0.6 to 1 part of dimethylaminopropylethylcarbamide to 40 to 60 parts of water to obtain an activated solution; add the activated solution to the sodium alginate solution, and keep stirring for 3 to 8 hours to obtain an activated mixture; S2. Add 0.4-0.6 parts of levodopa and 0.4-0.6 parts of 1,8-octanediamine to the activated mixture prepared in step S1, and adjust the pH to 4.5-6.5 with 0.5-2 mol / L hydrochloric acid, treat for 8-12 hours, terminate the reaction with 0.5-2 wt % sodium hydroxide aqueous solution, place the reaction mixture in a dialysis bag, and dialyze with water, the molecular weight cutoff of the dialysis bag is 3500-10000, after dialysis, wash the product with water 1-3 times, and freeze-dry at -40 to -80°C to obtain modified sodium alginate.
10. A compound Dendrobium officinale oral liquid, characterized in that: The preparation method is as described in any one of claims 1 to 9.
Citation Information
Patent Citations
A compound Dendrobium officinale oral liquid, and its preparation method
CN109223986A