Calcium zinc gluconate oral solution and preparation method thereof

Abstract

The invention belongs to the technical field of medicines, and provides a calcium zinc gluconate oral solution and a preparation method thereof. According to the invention, the sugar alcohol chelating agent is added into the calcium zinc gluconate oral solution, so that the effects of chelating and surface activity can be exerted at the same time, and the higher absorption and mobility of sugar alcohol can be utilized to drive calcium and zinc elements to be better absorbed. Preferably, sorbitol can form a sorbitol calcium ion chelate and a sorbitol zinc ion chelate with calcium ions in calcium gluconate and zinc ions in zinc gluconate, so that the stability and water solubility of the sorbitol calcium ion chelate and the sorbitol zinc ion chelate are improved, and precipitation of grape calcium carbonate and zinc gluconate is avoided; further, the solubility and the stability of the calcium gluconate and the zinc gluconate in the solution are improved. In addition, after the sorbitol is added, the low-temperature (2-8 DEG C) precipitation of the calcium gluconate is greatly improved. In addition, sorbitol has a fresh and sweet taste, so that the calcium zinc gluconate oral liquid has a good taste.

Description

Technical Field

[0001] The invention relates to the technical field of medicines, and in particular to a calcium zinc gluconate oral solution and a preparation method thereof. Background Art

[0002] Calcium gluconate zinc oral solution is used to treat diseases caused by calcium and zinc deficiency, including osteoporosis, tetany, bone dysplasia, rickets, calcium supplementation for pregnant, lactating and menopausal women, growth retardation in children, lack of appetite, anorexia, recurrent oral ulcers and acne, etc.

[0003] Since calcium gluconate in the calcium gluconate zinc oral solution is in a supersaturated state, the commercially available product has the problem of calcium gluconate precipitation during storage. Summary of the invention

[0004] In view of this, the object of the present invention is to provide a calcium gluconate zinc oral solution and a preparation method thereof. The calcium gluconate zinc oral solution provided by the present invention is not easy to precipitate during storage.

[0005] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0006] The present invention provides a calcium gluconate zinc oral solution, comprising the following components in mass concentrations:

[0007] Calcium gluconate 6%, zinc gluconate 0.3%, lysine hydrochloride 1%, chelating agent 1% to 25%, stabilizer 0% to 1%, sweetener 0.1% to 2%, antibacterial agent 0% to 0.3%, flavoring agent 0.1% to 2%, pH regulator 0% to 0.3%, and the balance is purified water;

[0008] The chelating agent is a sugar alcohol chelating agent, and the sugar alcohol chelating agent is one or more of sorbitol, mannitol, xylitol, erythritol and maltitol.

[0009] Preferably, the sweetener is one or more of cyclamate, sucralose, aspartame, acesulfame potassium, steviol glycoside, saccharin and saccharin sodium.

[0010] Preferably, the stabilizer is sodium chloride and / or sodium citrate.

[0011] Preferably, the antibacterial agent is one or more of benzoic acid, sodium benzoate, sorbic acid, potassium sorbate and paraben preservatives.

[0012] Preferably, the flavoring agent is lactic acid and / or essence; the essence is one or more of orange essence, sweet orange essence, blueberry essence, strawberry essence, peach essence, cherry essence, orange essence and apple essence.

[0013] Preferably, the pH adjuster is sodium hydroxide or calcium hydroxide.

[0014] Preferably, the pH value of the calcium zinc gluconate oral solution is 3.0-7.5.

[0015] The present invention also provides a method for preparing the calcium zinc gluconate oral solution described in the above technical scheme, comprising the following steps:

[0016] The calcium gluconate, zinc gluconate, lysine hydrochloride, chelating agent, antibacterial agent, stabilizer, flavoring agent, sweetener and pH regulator in the formula amount are dissolved in part of the purified water in sequence to obtain an initial solution; purified water is added to make up the volume, and after cooling to room temperature, the solution is filtered and sterilized to obtain the calcium gluconate zinc oral solution.

[0017] Preferably, the temperature range of heating when the material is dissolved is 50-100°C.

[0018] Preferably, the sterilization temperature is 100-125° C. and the time is 15-60 min.

[0019] The invention provides a calcium zinc gluconate oral solution.

[0020] The present invention adds a sugar alcohol chelating agent to the calcium gluconate zinc oral solution, which can play the role of chelation and surface activity at the same time, and can use the higher absorption and mobility of sugar alcohol to drive calcium and zinc elements to be better absorbed. The present invention further preferably uses sorbitol as the sugar alcohol chelating agent. Sorbitol has a chelating effect, and forms sorbitol calcium ion chelate and sorbitol zinc ion chelate with calcium ions in calcium gluconate and zinc ions in zinc gluconate. The present invention controls the mass concentration of sorbitol to be 1% to 25%, avoids the precipitation of calcium carbonate and zinc gluconate, and then increases the solubility and stability of calcium gluconate and zinc gluconate in the solution. Moreover, after sorbitol is added, the precipitation of calcium gluconate at low temperature (2 to 8° C.) is greatly improved. In addition, sorbitol has a sweet taste, which makes the taste of the calcium gluconate zinc oral solution good.

[0021] Furthermore, the sweetener used in the present invention is one or more of cyclamate, sucralose, aspartame, acesulfame potassium, steviol glycosides, saccharin and saccharin sodium, all of which are non-sugar sweeteners. Compared with adding sugar substances such as glucose and sucrose to the oral solution, the sweetener is more suitable for diabetic patients; at the same time, sucrose is not used as a sweetener, which avoids the problem of yellowing and discoloration of calcium gluconate zinc oral solution at high temperature. DETAILED DESCRIPTION

[0022] The present invention provides a calcium gluconate zinc oral solution, comprising the following components in mass concentrations:

[0023] Calcium gluconate 6%, zinc gluconate 0.3%, lysine hydrochloride 1%, sorbitol 1%-25%, stabilizer 0%-1%, sweetener 0.1%-2%, antibacterial agent 0%-0.3%, flavoring agent 0.1%-2%, pH regulator 0%-0.3%, and the balance is purified water;

[0024] The chelating agent is a sugar alcohol chelating agent, and the sugar alcohol chelating agent is one or more of sorbitol, mannitol, xylitol, erythritol and maltitol.

[0025] In the present invention, unless otherwise specified, the raw materials used in the present invention are preferably commercially available products.

[0026] The calcium gluconate zinc oral solution provided by the present invention comprises calcium gluconate with a mass concentration of 6%. In the present invention, the calcium gluconate is the active ingredient of the oral solution.

[0027] The calcium zinc gluconate oral solution provided by the present invention comprises zinc gluconate with a mass concentration of 0.3%. In the present invention, the zinc gluconate is the active ingredient of the oral solution.

[0028] The calcium gluconate zinc oral solution provided by the invention comprises lysine hydrochloride with a mass concentration of 1%. In the invention, the lysine hydrochloride has the functions of promoting protein synthesis and metabolism, promoting human development, and enhancing immune function.

[0029] The calcium gluconate zinc oral solution provided by the present invention comprises a chelating agent with a mass concentration of 1% to 25%, and the mass concentration of the chelating agent can specifically be 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24% or 25%, etc. In the present invention, the chelating agent is a sugar alcohol chelating agent, and the sugar alcohol chelating agent is one or more of sorbitol, mannitol, xylitol, erythritol and maltitol, preferably sorbitol. In the present invention, the sugar alcohol chelating agent can simultaneously play the role of chelation and surface activity, and can utilize the higher absorption and mobility of sugar alcohol to drive calcium and zinc elements to be better absorbed. The present invention further preferably uses sorbitol as a sugar alcohol chelating agent. Sorbitol can form sorbitol calcium ion chelate and sorbitol zinc ion chelate with calcium ions in calcium gluconate and zinc ions in zinc gluconate. The present invention controls the mass concentration of sorbitol to be 1% to 25%, thereby avoiding the precipitation of calcium gluconate and zinc gluconate, thereby increasing the solubility and stability of calcium gluconate and zinc gluconate in the solution. Moreover, after the addition of sorbitol, the precipitation of calcium gluconate at low temperature (2 to 8° C.) is greatly improved. In addition, sorbitol has a sweet taste, which makes the taste of calcium gluconate zinc oral solution good.

[0030] The calcium gluconate zinc oral solution provided by the present invention includes a stabilizer with a mass concentration of 0% to 1%, preferably 0.01% to 1%, more preferably 0.1 to 1%, more preferably 0.1% to 0.5%, specifically 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9% or 1.0%, etc. In the present invention, the stabilizer is preferably sodium chloride and / or sodium citrate, specifically sodium chloride is preferably. In the present invention, the stabilizer, especially sodium chloride, reduces the concentration of weak electrolyte molecules, increases the ion concentration, increases the degree of dissociation, and increases the solubility of calcium gluconate and zinc gluconate through the salt effect.

[0031] The calcium gluconate zinc oral solution provided by the present invention comprises a sweetener with a mass concentration of 0.1% to 2%, preferably 0.1% to 1%, specifically 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9% or 2%, etc. In the present invention, the sweetener is preferably one or more of sodium cyclamate, sucralose, aspartame, acesulfame potassium, steviol glycoside, saccharin and sodium saccharin, specifically preferably sodium cyclamate. In the present invention, the sweetener is one or more of sweeteners such as cyclamate, sucralose, aspartame, acesulfame potassium, steviol glycosides, saccharin and saccharin sodium, all of which are non-sugar sweeteners. Compared with adding sugar substances such as glucose and sucrose to the oral solution, it is more suitable for diabetic patients; at the same time, sucrose is not used as a sweetener, which avoids the problem of yellowing and discoloration of calcium gluconate zinc oral solution at high temperature.

[0032] The calcium gluconate zinc oral solution provided by the present invention comprises an antibacterial agent with a mass concentration of 0% to 0.3%, preferably 0.01 to 0.3%, more preferably 0.04% to 0.3%, more preferably 0.04% to 0.15%, specifically 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.11%, 0.12%, 0.13%, 0.14%, 0.15%, 0.2%, 0.25% or 0.3%, etc. In the present invention, the antibacterial agent is preferably one or more of benzoic acid, sodium benzoate, sorbic acid, potassium sorbate and paraben preservatives, specifically preferably sodium benzoate.

[0033] The calcium gluconate zinc oral solution provided by the present invention includes a flavoring agent having a mass concentration of 0.1% to 2%, preferably 0.1% to 1%, specifically 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.25%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9% or 2%, etc. In the present invention, the flavoring agent is preferably lactic acid and / or essence, specifically preferably lactic acid and essence. In the present invention, the essence is preferably one or more of orange essence, sweet orange essence, blueberry essence, strawberry essence, peach essence, cherry essence, orange essence and apple essence, etc., further preferably orange essence.

[0034] The calcium gluconate zinc oral solution provided by the present invention comprises a pH regulator with a mass concentration of 0% to 0.3%, preferably 0.01% to 0.3%, more preferably 0.04% to 0.3%, more preferably 0.04% to 0.15%, specifically 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.11%, 0.12%, 0.13%, 0.14%, 0.15%, 0.2%, 0.25% or 0.3%, etc. In the present invention, the pH regulator is sodium hydroxide or calcium hydroxide, preferably sodium hydroxide.

[0035] The calcium zinc gluconate oral solution provided by the invention comprises the balance of purified water.

[0036] In the present invention, the pH value of the calcium zinc gluconate oral solution is preferably 3.0 to 7.5.

[0037] The present invention also provides a method for preparing the calcium zinc gluconate oral solution described in the above technical scheme, comprising the following steps:

[0038] The calcium gluconate, zinc gluconate, lysine hydrochloride, chelating agent, antibacterial agent, stabilizer, flavoring agent, sweetener and pH regulator in the formula amount are heated and dissolved in part of purified water to obtain an initial solution; purified water is added to make up the volume, and after cooling to room temperature, the solution is filtered and sterilized to obtain the calcium gluconate zinc oral solution.

[0039] In the present invention, the partially purified water is preferably 70-90% of the total amount of the purified water in the formula. In the present invention, the temperature range of heating when the material is dissolved, that is, the dissolution temperature is preferably 50-100° C. In the present invention, the dissolution is preferably carried out in a liquid preparation tank.

[0040] In the present invention, the step of heating and dissolving the formulated amount of calcium gluconate, zinc gluconate, lysine hydrochloride, chelating agent, antibacterial agent, stabilizer, flavoring agent, sweetener and pH regulator in partially purified water preferably comprises: placing the partially purified water in a liquid preparation tank, heating it to 50-100° C., adding the formulated amount of calcium gluconate, zinc gluconate, lysine hydrochloride, chelating agent, antibacterial agent and stabilizer, stirring and dissolving, adjusting the pH value to a suitable range with a pH regulator, obtaining an initial solution, adding purified water to make up the volume, cooling it to room temperature, filtering and sterilizing, and obtaining the calcium gluconate zinc oral solution.

[0041] In the present invention, the pore size of the filter element used for filtration is preferably 0.2 μm to 0.45 μm.

[0042] In the present invention, the sterilization temperature is preferably 100-125°C, specifically 100°C, 105°C, 110°C, 115°C, 120°C or 125°C, and the sterilization time is preferably 15-60 min, specifically 15 min, 30 min, 45 min or 60 min.

[0043] The calcium gluconate zinc oral solution and the preparation method thereof provided by the present invention are described in detail below in conjunction with the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0044] Example

[0045] The recipe is shown in Table 1.

[0046] Table 1 Formula composition of the embodiment and comparative example calcium gluconate zinc oral solution

[0047]

[0048] The preparation method is:

[0049] Take 80% of the total amount of purified water into a liquid preparation tank, heat it to 50-100°C, add the formulated amount of lactic acid, and stir to dissolve; then add the formulated amounts of calcium gluconate, zinc gluconate, lysine hydrochloride, sorbitol, sodium benzoate and sodium chloride in turn, and stir to dissolve; stop heating, and add cyclamate and orange essence when the temperature is cooled to below 40°C, continue stirring until completely dissolved, test the pH value of the solution, and if necessary, add sodium hydroxide to adjust to an appropriate pH value; add purified water to make up to the full volume; when the above solution is cooled to room temperature, filter it into a liquid storage tank with a 0.2μm-0.45μm filter element, fill it, roll-cap and seal it, and sterilize it in a sterilizer at 105°C for 45 minutes.

[0050] The pH value of the obtained calcium gluconate zinc oral solution was determined by the pharmacopoeia pH determination method; the contents of calcium and zinc in the obtained calcium gluconate zinc oral solution were determined by titration, the content of lysine hydrochloride in the obtained calcium gluconate zinc oral solution was determined by high performance liquid chromatography, and the taste acceptance of the sample was evaluated by a blind method; the obtained calcium gluconate zinc oral solution was placed at 2-8°C to observe its low-temperature precipitation; the obtained calcium gluconate zinc oral solution was placed at 60°C to observe its high-temperature color change. The results are shown in Table 2.

[0051] Table 2 Test results of calcium gluconate zinc oral solution obtained from the examples and comparative examples

[0052]

[0053]

[0054] It can be seen from Table 1 and Table 2 that: through the stability test and taste recognition survey, the embodiment adds more than 1% sorbitol compared with the comparative example 1, and has obvious advantages in low-temperature precipitation and taste. When the amount of sorbitol in the comparative example 3 is less than 1%, the improvement effect of low-temperature precipitation is not obvious, and the taste is relatively poor; sucrose is used as a sweetener in the comparative example 2, and the taste is good, but the stability of low-temperature precipitation and high-temperature discoloration is worse than that of the comparative example, and it is not an optimal solution formula. The calcium gluconate zinc oral solution provided by the present invention has obvious advantages.

[0055] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A calcium zinc gluconate oral solution, characterized in that: The following components are included in mass concentration: Calcium gluconate 6%, zinc gluconate 0.3%, lysine hydrochloride 1%, chelating agent 1% to 25%, stabilizer 0% to 1%, sweetener 0.1% to 2%, antibacterial agent 0% to 0.3%, flavoring agent 0.1% to 2%, pH regulator 0% to 0.3%, and the balance is purified water; The chelating agent is a sugar alcohol chelating agent, and the sugar alcohol chelating agent is one or more of sorbitol, mannitol, xylitol, erythritol and maltitol.

2. The calcium gluconate zinc oral solution according to claim 1, characterized in that The sweetener is one or more of sodium cyclamate, sucralose, aspartame, acesulfame potassium, steviol glycoside, saccharin and saccharin sodium.

3. The calcium gluconate zinc oral solution according to claim 1, characterized in that The stabilizer is sodium chloride and / or sodium citrate.

4. The calcium gluconate zinc oral solution according to claim 1, characterized in that The antibacterial agent is one or more of benzoic acid, sodium benzoate, sorbic acid, potassium sorbate and paraben preservatives.

5. The calcium gluconate zinc oral solution according to claim 1, characterized in that The flavoring agent is lactic acid and / or essence; the essence is one or more of orange essence, sweet orange essence, blueberry essence, strawberry essence, peach essence, cherry essence, orange essence and apple essence.

6. The calcium gluconate zinc oral solution according to claim 1, characterized in that The pH regulator is sodium hydroxide or calcium hydroxide.

7. The calcium gluconate zinc oral solution according to any one of claims 1 to 6, characterized in that: The pH value of the calcium zinc gluconate oral solution is 3.0-7.

5.

8. The method for preparing the calcium zinc gluconate oral solution according to any one of claims 1 to 7, characterized in that: The following steps are involved: The calcium gluconate, zinc gluconate, lysine hydrochloride, chelating agent, antibacterial agent, stabilizer, flavoring agent, sweetener and pH regulator in the formula amount are dissolved in part of the purified water in sequence to obtain an initial solution; purified water is added to make up the volume, and after cooling to room temperature, the solution is filtered and sterilized to obtain the calcium gluconate zinc oral solution.

9. The preparation method according to claim 8, characterized in that: The temperature range of heating when the material is dissolved is 50-100°C.

10. The preparation method according to claim 8, characterized in that: The sterilization temperature is 100-125° C. and the sterilization time is 15-60 minutes.

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