Compound dextromethorphan hydrobromide syrup and preparation method thereof

Abstract

The invention belongs to the technical field of cough relieving and phlegm eliminating medicines, and particularly relates to compound dextromethorphan hydrobromide syrup and a preparation method thereof. On the basis that the total volume of the compound dextromethorphan hydrobromide syrup is 1000L, the compound dextromethorphan hydrobromide syrup provided by the invention is prepared from the following components: 3000g of dextromethorphan hydrobromide, 20kg of guaiacol glyceryl ether, 650kg of cane sugar, 100L of 1, 2-propylene glycol, 2000g of benzoic acid, 200g of sodium benzoate, 100g of menthol, 4000mL of essence, 14000mL of ethanol, 2000mL of caramel pigment and the balance of purified water. The compound dextromethorphan hydrobromide syrup provided by the invention takes benzoic acid as a main preservative and is matched with sodium benzoate; meanwhile, the dosage ratio of all the components in the syrup is optimized, the obtained compound dextromethorphan hydrobromide syrup is good in preservative effect, and adverse reactions are reduced.

Description

Technical Field

[0001] The present invention belongs to the technical field of antitussive and expectorant drugs, and particularly relates to a compound dextromethorphan hydrobromide syrup and a preparation method thereof. Background Art

[0002] A cold is an upper respiratory tract infection caused by a variety of viruses, commonly known as "common cold", which is a common respiratory disease that can occur throughout the year. It has extensive epidemicity and infectivity. If not controlled in time, it can cause complications such as viral pneumonia and myocarditis, seriously endangering human health. Clinically, a cold is divided into common cold and influenza. Bronchitis is a common disease among middle-aged and elderly people in winter. It mostly develops from acute bronchitis that is not cured in time. Clinically, it is often manifested as cough, expectoration, or accompanied by shortness of breath, wheezing, etc. In severe cases, it can be complicated by emphysema, pulmonary heart disease, etc., seriously affecting people's work and life.

[0003] The symptoms of cold and bronchitis mostly mainly include cough and expectoration. Cough is a defensive reflex activity generated when the respiratory system is stimulated. Sputum is the product of respiratory tract inflammation, which can stimulate the respiratory tract mucosa to cause cough and aggravate the infection. Therefore, antitussive and expectorant drugs must be used to relieve the condition.

[0004] Currently, there are many drugs used for antitussive or expectorant. In clinical applications such as dextromethorphan hydrobromide capsules and mucosolvan, these drugs only target one of the symptoms of antitussive and expectoration, and it is difficult to achieve the effect of simultaneous treatment. There are also some first-line clinical drugs that cannot meet the market requirements due to reasons such as drug dependence and relatively large side effects.

[0005] The compound dextromethorphan hydrobromide preparation is specifically developed for the above two main symptoms. Dextromethorphan hydrobromide is a central antitussive drug that acts by inhibiting the cough center in the medulla oblongata. Its antitussive effect is equivalent to that of codeine, but it has no analgesic effect, weak addiction and tolerance, and the therapeutic dose will not inhibit respiration. Guaifenesin glyceryl ether is an expectorant that causes nausea. After oral administration, it stimulates the gastric mucosa and reflexively causes an increase in bronchial secretion, reducing the viscosity of sputum and producing an expectorant effect.

[0006] However, since the compound dextromethorphan hydrobromide syrup is easily contaminated by fungi, yeasts and other microorganisms, making the syrup turbid and deteriorated, preservatives are often added to the syrup. Currently, the preservative commonly used for drugs is benzoic acid, but its antiseptic effect is poor and there are many adverse reactions. [[ID=2,2]]Summary of the Invention

[0007] The purpose of the present invention is to provide a compound dextromethorphan hydrobromide syrup and a preparation method thereof. The compound dextromethorphan hydrobromide syrup provided by the present invention has good antiseptic effect and reduced adverse reactions.

[0008] To achieve the above object, the present invention provides the following technical solutions:

[0009] The present invention provides a compound dextromethorphan hydrobromide syrup. Based on the total volume of the compound dextromethorphan hydrobromide syrup being 1000 L, it includes the following components:

[0010] 3000 g of dextromethorphan hydrobromide, 20 kg of guaifenesin glycerol ether, 650 kg of sucrose, 100 L of 1,2 - propylene glycol, 2000 g of benzoic acid, 200 g of sodium benzoate, 100 g of menthol, 4000 mL of essence, 14000 mL of ethanol, 2000 mL of caramel pigment, and the balance of purified water.

[0011] Preferably, the essence is apple essence.

[0012] Preferably, the compound dextromethorphan hydrobromide syrup is a light yellowish - brown clear liquid; the pH value is 3.2 - 4.3; and the relative density is 1.21 - 1.26.

[0013] The present invention provides a preparation method of the compound dextromethorphan hydrobromide syrup described in the above technical solution, including the following steps:

[0014] Boil sucrose, caramel pigment, and purified water, and then perform solid - liquid separation and cooling in sequence to obtain syrup;

[0015] Mix and dissolve dextromethorphan hydrobromide, menthol, benzoic acid, sodium benzoate, and ethanol, and then mix with the first hot water and perform solid - liquid separation to obtain a dextromethorphan hydrobromide mixed solution. The first hot water is purified water heated.

[0016] Dissolve guaifenesin glycerol ether in the second hot water, and then perform solid - liquid separation to obtain a guaifenesin glycerol ether solution. The second hot water is purified water heated.

[0017] Mix the dextromethorphan hydrobromide mixed solution, the guaifenesin glycerol ether solution, the 1,2 - propylene glycol after solid - liquid separation, the essence after solid - liquid separation, and the syrup, and then add the third hot water to obtain a liquid medicine. The third hot water is purified water heated.

[0018] Cool the liquid medicine, perform pre - filling inspection, solid - liquid separation, and filling in sequence to obtain the compound dextromethorphan hydrobromide syrup.

[0019] Preferably, boiling sucrose, caramel pigment, and purified water includes: adding the sucrose to the purified water and boiling, and then adding the sucrose pigment and boiling.

[0020] Preferably, the temperature of the syrup is 45 - 55 °C.

[0021] Preferably, the temperature of the first hot water is 70 - 85 °C.

[0022] Preferably, the temperature of the second hot water is 70 - 85°C; the temperature of the third hot water is 90 - 100°C.

[0023] Preferably, the temperature of the cooling is ≤50°C.

[0024] Preferably, the items for inspection before filling include: appearance, pH value, relative density, content of dextromethorphan hydrobromide, content of guaifenesin, content of benzoic acid, content of sodium benzoate.

[0025] The present invention provides a compound dextromethorphan hydrobromide syrup. Based on the total volume of the compound dextromethorphan hydrobromide syrup being 1000 L, it includes the following components: 3000 g of dextromethorphan hydrobromide, 20 kg of guaifenesin, 650 kg of sucrose, 100 L of 1,2 - propylene glycol, 2000 g of benzoic acid, 200 g of sodium benzoate, 100 g of menthol, 4000 mL of essence, 14000 mL of ethanol, 2000 mL of caramel pigment, and the balance of purified water. The compound dextromethorphan hydrobromide syrup provided by the present invention uses benzoic acid as the main preservative and is paired with sodium benzoate at the same time; meanwhile, the dosage ratio of each component in the syrup is optimized, and the obtained compound dextromethorphan hydrobromide syrup has good anti - corrosion effect and reduced adverse reactions. Description of the Drawings

[0026] Figure 1 It is the preparation flow chart of the compound dextromethorphan hydrobromide syrup provided by the present invention. Detailed Embodiments

[0027] The present invention provides a compound dextromethorphan hydrobromide syrup. Based on the total volume of the compound dextromethorphan hydrobromide syrup being 1000 L, it includes the following components:

[0028] 3000 g of dextromethorphan hydrobromide, 20 kg of guaifenesin, 650 kg of sucrose, 100 L of 1,2 - propylene glycol, 2000 g of benzoic acid, 200 g of sodium benzoate, 100 g of menthol, 4000 mL of essence, 14000 mL of ethanol, 2000 mL of caramel pigment, and the balance of purified water.

[0029] In the present invention, unless otherwise specified, all preparation raw materials / components are commercially available products well - known to those skilled in the art.

[0030] Based on the total volume of the compound dextromethorphan hydrobromide syrup being 1000 L, the components of the compound dextromethorphan hydrobromide syrup provided by the present invention include 3000 g of dextromethorphan hydrobromide.

[0031] Based on the total volume of the compound dextromethorphan hydrobromide syrup being 1000 L, the components of the compound dextromethorphan hydrobromide syrup provided by the present invention include 20 kg of guaifenesin.

[0032] Based on the total volume of the compound dextromethorphan hydrobromide syrup being 1000 L, the components of the compound dextromethorphan hydrobromide syrup provided by the present invention include 650 kg of sucrose.

[0033] Based on the total volume of the compound dextromethorphan hydrobromide syrup being 1000 L, the components of the compound dextromethorphan hydrobromide syrup provided by the present invention include 100 L of 1,2 - propylene glycol.

[0034] Based on the total volume of the compound dextromethorphan hydrobromide syrup being 1000 L, the components of the compound dextromethorphan hydrobromide syrup provided by the present invention include 2000 g of benzoic acid.

[0035] Based on the total volume of the compound dextromethorphan hydrobromide syrup being 1000 L, the components of the compound dextromethorphan hydrobromide syrup provided by the present invention include 200 g of sodium benzoate.

[0036] Based on the total volume of the compound dextromethorphan hydrobromide syrup being 1000 L, the components of the compound dextromethorphan hydrobromide syrup provided by the present invention include 100 g of menthol.

[0037] Based on the total volume of the compound dextromethorphan hydrobromide syrup being 1000 L, the components of the compound dextromethorphan hydrobromide syrup provided by the present invention include 4000 mL of essence. In the present invention, the essence is preferably apple essence.

[0038] Based on the total volume of the compound dextromethorphan hydrobromide syrup being 1000 L, the components of the compound dextromethorphan hydrobromide syrup provided by the present invention include 14000 mL of ethanol.

[0039] Based on the total volume of the compound dextromethorphan hydrobromide syrup being 1000 L, the components of the compound dextromethorphan hydrobromide syrup provided by the present invention include 2000 mL of caramel color.

[0040] Based on the total volume of the compound dextromethorphan hydrobromide syrup being 1000 L, the components of the compound dextromethorphan hydrobromide syrup provided by the present invention include the balance of purified water.

[0041] As an embodiment of the present invention, the compound dextromethorphan hydrobromide syrup comprises: 3000 g of dextromethorphan hydrobromide, 20 kg of guaifenesin glycerol ether, 650 kg of sucrose, 100 L of 1,2 - propylene glycol, 2000 g of benzoic acid, 200 g of sodium benzoate, 100 g of menthol, 4000 mL of essence, 14000 mL of ethanol, 2000 mL of caramel pigment, and the balance of purified water, with a total volume of 1000 L.

[0042] As an embodiment of the present invention, the compound dextromethorphan hydrobromide syrup comprises: 3 g of dextromethorphan hydrobromide, 20 g of guaifenesin glycerol ether, 650 g of sucrose, 100 mL of 1,2 - propylene glycol, 2 g of benzoic acid, 0.2 g of sodium benzoate, 0.1 g of menthol, 4 mL of essence, 14 mL of ethanol, 2 mL of caramel pigment, and the balance of purified water, with a total volume of 1000 mL.

[0043] In the present invention, the compound dextromethorphan hydrobromide syrup preferably has the following properties: it is a brown - yellow clear liquid; it tastes sweet and has an aromatic odor. The pH value of the compound dextromethorphan hydrobromide syrup is preferably 3.2 - 4.3. The relative density of the compound dextromethorphan hydrobromide syrup is preferably 1.21 - 1.26.

[0044] In the present invention, the indications of the compound dextromethorphan hydrobromide syrup preferably include: for cough and expectoration caused by upper respiratory tract infections (such as common cold and influenza), bronchitis, etc.

[0045] In the present invention, the usage and dosage of the compound dextromethorphan hydrobromide syrup are preferably as follows: oral administration. For adults, 10 mL once, 3 times a day, and no more than 4 times in 24 hours.

[0046] In the present invention, the specification of the compound dextromethorphan hydrobromide syrup is preferably: 100 mL contains 0.3 g of dextromethorphan hydrobromide and 2.0 g of guaifenesin glycerol ether.

[0047] In the present invention, the packaging of the compound dextromethorphan hydrobromide syrup is preferably: packaged in a medicinal plastic bottle, with each bottle containing 100 mL. 100 mL / bottle × 120 bottles / box.

[0048] In the present invention, the storage conditions of the compound dextromethorphan hydrobromide syrup preferably include: stored in a dark place, sealed, and placed in a cool place (not exceeding 20°C).

[0049] In the present invention, the validity period of the compound dextromethorphan hydrobromide syrup is preferably 24 months.

[0050] The present invention provides a preparation method of the compound dextromethorphan hydrobromide syrup according to the above - mentioned technical solution, comprising the following steps:

[0051] Sucrose, caramel color, and purified water are boiled and then subjected to solid-liquid separation and cooling in sequence to obtain syrup;

[0052] Dextromethorphan hydrobromide, menthol, benzoic acid, sodium benzoate, and ethanol are mixed and dissolved, and then mixed with first hot water and subjected to solid-liquid separation to obtain a dextromethorphan hydrobromide mixed solution, where the first hot water is purified water after heating;

[0053] Guaifenesin is dissolved in second hot water and then subjected to solid-liquid separation to obtain a guaifenesin solution, where the second hot water is purified water after heating;

[0054] The dextromethorphan hydrobromide mixed solution, the guaifenesin solution, 1,2-propanediol after solid-liquid separation, essence after solid-liquid separation, and syrup are mixed, and then third hot water is added to obtain a medicinal liquid;

[0055] The medicinal liquid is cooled, inspected before filling, subjected to solid-liquid separation, and filled in sequence to obtain the compound dextromethorphan hydrobromide syrup.

[0056] In the present invention, sucrose, caramel color, and purified water are boiled and then subjected to solid-liquid separation and cooling in sequence to obtain syrup. In the present invention, the boiling of the sucrose, caramel color, and purified water preferably includes: adding the sucrose to the purified water and boiling, and then adding the sucrose pigment and boiling. The dosage ratio of the sucrose to the purified water is preferably 650 g: 650 mL. The solid-liquid separation is preferably filtration. The temperature of the syrup obtained after cooling is preferably 45 - 55 °C, and can be 50 °C in the examples.

[0057] In the present invention, dextromethorphan hydrobromide, menthol, benzoic acid, sodium benzoate, and ethanol are mixed and dissolved, and then mixed with first hot water and subjected to solid-liquid separation to obtain a dextromethorphan hydrobromide mixed solution, where the first hot water is purified water after heating. In the present invention, the mixing and dissolving are preferably carried out under stirring conditions. The temperature of the first hot water is preferably 70 - 85 °C, more preferably 80 °C. The mixing is preferably carried out under stirring conditions. In the present invention, after dextromethorphan hydrobromide, menthol, benzoic acid, sodium benzoate, and ethanol are mixed and dissolved and then mixed with the first hot water, a clear solution is obtained, and then the clear solution is subjected to the solid-liquid separation. The solid-liquid separation is preferably filtration.

[0058] In the present invention, guaifenesin is dissolved in second hot water and then subjected to solid-liquid separation to obtain a guaifenesin solution, where the second hot water is purified water after heating. In the present invention, the temperature of the second hot water is 70 - 85 °C, more preferably 80 °C. The solid-liquid separation is preferably filtration.

[0059] After obtaining the dextromethorphan hydrobromide mixed solution and the guaifenesin glycerol ether solution, the present invention mixes the dextromethorphan hydrobromide mixed solution, the guaifenesin glycerol ether solution, the 1,2-propanediol after solid-liquid separation, the essence after solid-liquid separation, and the syrup, and then adds the third hot water to obtain the liquid medicine, wherein the third hot water is purified water after heating. In the present invention, the 1,2-propanediol after solid-liquid separation is preferably 1,2-propanediol after filtration. The essence after solid-liquid separation is preferably essence after filtration. The present invention preferably adds the dextromethorphan hydrobromide mixed solution, the guaifenesin glycerol ether solution, the 1,2-propanediol after solid-liquid separation, and the essence after solid-liquid separation to the syrup respectively. In the examples of the present invention, the dextromethorphan hydrobromide mixed solution, the guaifenesin glycerol ether solution, the 1,2-propanediol after solid-liquid separation, and the essence after solid-liquid separation are added to the syrup in sequence. The temperature of the third hot water is preferably 90-100 °C.

[0060] After obtaining the liquid medicine, the present invention cools, checks before filling, separates solid and liquid, and fills the liquid medicine in sequence to obtain the compound dextromethorphan hydrobromide syrup. In the present invention, the temperature of the cooling is preferably ≤ 50 °C. In the present invention, the cooling obtains an intermediate product, and the present invention preferably conducts the check before filling (i.e., Figure 1 the check of the intermediate product in

[0061] on the intermediate product). The items of the check before filling preferably include: appearance, pH value, relative density, content of dextromethorphan hydrobromide, content of guaifenesin glycerol ether, content of benzoic acid, and content of sodium benzoate. The solid-liquid separation is preferably filtration. The filling preferably uses a medicinal plastic bottle for packaging and an aluminum-plastic combination cap at the same time. In the present invention, after the filling, the present invention preferably further includes conducting the filling quantity check, lamp inspection packaging, and sampling inspection in sequence, and finally storing the product in the warehouse. The filling quantity check is preferably the filling quantity difference check. The items of the sampling inspection preferably include appearance, relative density, pH value, content test, and microorganisms, and the content determination preferably includes the content of dextromethorphan hydrobromide, the content of guaifenesin glycerol ether, the content of benzoic acid, and the content of sodium benzoate.

[0062] Table 1 Items and Contents of Inspection

[0063]

[0064] In order to further illustrate the present invention, the technical solutions provided by the present invention will be described in detail below in conjunction with the examples, but they cannot be understood as limiting the protection scope of the present invention.

[0065] The following examples are carried out in accordance with Figure 1Prepare the compound dextromethorphan hydrobromide syrup according to the flow chart shown below. The essence used in the following examples is apple essence.

[0066] Example 1

[0067] This example provides a preparation method for compound dextromethorphan hydrobromide syrup, including the following steps:

[0068] (1) Weigh 650 g of sucrose, add 650 mL of purified water, boil until the sucrose dissolves, add 2 mL of caramel colorant and boil, filter, and cool to 50 °C.

[0069] (2) Weigh 3 g of dextromethorphan hydrobromide, 0.1 g of menthol, 2 g of benzoic acid, and 0.2 g of sodium benzoate, stir and dissolve with 14 mL of ethanol, add hot water (purified water) at 80 °C and stir until completely dissolved and clear, then filter. Add the filtrate to the syrup in step (1).

[0070] (3) Weigh 20 g of guaifenesin glycerol ether, add hot water (purified water) at 80 °C and stir until dissolved and clear, then filter. Add the filtrate to the syrup in step (1).

[0071] (4) Measure 100 mL of 1,2 - propylene glycol and 4 mL of essence respectively, filter them in sequence and add them to the syrup in step (1).

[0072] (5) Finally, add an appropriate amount of boiling water to make 1000 mL, stir well, wait until the temperature of the liquid medicine cools below 50 °C, filter and fill it after passing the inspection according to the content in Table 1 to obtain the product.

[0073] Example 2:

[0074] This example provides a preparation method for compound dextromethorphan hydrobromide syrup, including the following steps:

[0075] (1) Weigh 650 kg of sucrose, add 650 L of purified water, boil until the sucrose dissolves, add 2000 mL of caramel colorant and boil, filter with filter paper, and cool to 50 °C.

[0076] (2) Weigh 3000 g of dextromethorphan hydrobromide, 100 g of menthol, 2000 g of benzoic acid, and 200 g of sodium benzoate, stir and dissolve with 14 L of ethanol, add hot water (purified water) at 80 °C and stir until completely dissolved and clear, then filter. Add the filtrate to the syrup in step (1).

[0077] (3) Weigh 20 kg of guaifenesin glycerol ether, add hot water (purified water) at 80 °C and stir until dissolved and clear, then filter. Add the filtrate to the syrup in step (1).

[0078] (4) Measure 100 L of 1,2 - propylene glycol and 4 L of essence respectively, filter them in sequence and add them to the syrup in step (1);

[0079] (5) Finally, add appropriate amount of boiling water to make up to 1000 L, stir well, wait for the temperature of the liquid medicine to cool below 50 °C, filter and fill after passing the inspection according to the content of Table 1 to obtain the product.

[0080] It can be seen from the above examples that the compound dextromethorphan hydrobromide syrup provided by the present invention uses benzoic acid as the main preservative and is paired with sodium benzoate at the same time; meanwhile, the dosage ratio of each component in the syrup is optimized, and the obtained compound dextromethorphan hydrobromide syrup has good anti - corrosion effect and reduced adverse reactions.

[0081] Although the above examples have described the present invention in detail, they are only a part of the embodiments of the present invention, not all embodiments. Other embodiments can be obtained based on these embodiments without creative efforts, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A compound dextromethorphan hydrobromide syrup, characterized in that, Based on the total volume of the compound dextromethorphan hydrobromide syrup being 1000 L, it includes the following components: 3000 g of dextromethorphan hydrobromide, 20 kg of guaifenesin glyceryl ether, 650 kg of sucrose, 100 L of 1,2 - propanediol, 2000 g of benzoic acid, 200 g of sodium benzoate, 100 g of menthol, 4000 mL of essence, 14000 mL of ethanol, 2000 mL of caramel pigment, and the balance of purified water.

2. The compound dextromethorphan hydrobromide syrup according to claim 1, characterized in that, The essence is apple essence.

3. The compound dextromethorphan hydrobromide syrup according to claim 1 or 2, characterized in that, The compound dextromethorphan hydrobromide syrup is a brownish - yellow clear liquid; its pH value is 3.2 - 4.3; and its relative density is 1.21 - 1.

26.

4. The preparation method of the compound dextromethorphan hydrobromide syrup according to any one of claims 1 to 3, characterized in that, It includes the following steps: Boil sucrose, caramel pigment, and purified water, then perform solid - liquid separation and cooling in sequence to obtain syrup. Mix and dissolve dextromethorphan hydrobromide, menthol, benzoic acid, sodium benzoate, and ethanol, then mix with the first hot water (heated purified water) and perform solid - liquid separation to obtain the dextromethorphan hydrobromide mixed solution. Dissolve guaifenesin glyceryl ether in the second hot water (heated purified water), then perform solid - liquid separation to obtain the guaifenesin glyceryl ether solution. Mix the dextromethorphan hydrobromide mixed solution, the guaifenesin glyceryl ether solution, the solid - liquid separated 1,2 - propanediol, the solid - liquid separated essence, and the syrup, then add the third hot water (heated purified water) to obtain the medicinal liquid. Cool the medicinal liquid, perform pre - filling inspection, solid - liquid separation, and filling in sequence to obtain the compound dextromethorphan hydrobromide syrup.

5. The preparation method according to claim 4, wherein The boiling of sucrose, caramel pigment, and purified water includes: adding the sucrose to the purified water and boiling, then adding the sucrose pigment and boiling.

6. The preparation method according to claim 4 or 5, characterized in that, The temperature of the syrup is 45 - 55 °C.

7. The preparation method according to claim 4, characterized in that, The temperature of the first hot water is 70 - 85 °C.

8. The preparation method according to claim 4, characterized in that, The temperature of the second hot water is 70 - 85 °C; the temperature of the third hot water is 90 - 100 °C.

9. The preparation method according to claim 4, characterized in that, The temperature of the cooling is ≤ 50 °C.

10. The preparation method according to claim 4, characterized in that, The items for pre - filling inspection include: appearance, pH value, relative density, content of dextromethorphan hydrobromide, content of guaifenesin glyceryl ether, content of benzoic acid, content of sodium benzoate.

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