Ferrous succinate nano suspension as well as preparation method and application thereof

Abstract

The invention relates to a ferrous succinate nanosuspension as well as a preparation method and application thereof, and belongs to the field of pharmaceutical preparations. The ferrous succinate nano suspension provided by the invention comprises ferrous succinate and a stabilizer, and the mass ratio of the ferrous succinate to the stabilizer is 1: 1-1: 10; the preparation method comprises the following steps: stirring and dispersing ferrous succinate and a stabilizer in water, and homogenizing at high pressure. According to the invention, ferrous succinate and a safe and nontoxic stabilizer with good biocompatibility are subjected to stirring dispersion mechanical force and high-pressure homogeneous cavitation force in water, so that the particle size of the system is reduced to a nanometer level, and a stable suspension system is formed by virtue of solubilization, suspending assistance and steric hindrance effects of the stabilizer; the solubility and the dispersity of the ferrous succinate in water are improved. Furthermore, the ferrous succinate nanosuspension is used as a drug intermediate to prepare a ferrous succinate nanosuspension preparation, and the problems that a traditional ferrous succinate preparation is difficult to absorb, low in bioavailability and poor in administration compliance are solved.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical preparations, and particularly relates to a ferrous succinate nano-suspension, a preparation method thereof, and an application thereof. Background Art

[0002] Iron is an important component of human hemoglobin, cytochrome enzymes, and many reductases, and is involved in the transportation of oxygen and carbon dioxide, as well as oxidation-reduction and metabolic processes, and is indispensable for the normal physiological activities of the body. Insufficient iron intake will consume the body's iron reserves, and then cause iron deficiency anemia (IDA), accompanied by symptoms such as fatigue, restlessness, mood or cognitive disorders, and memory loss, seriously affecting people's physical health and reducing the quality of life.

[0003] Approximately one-third of the global population suffers from iron deficiency anemia. In particular, iron deficiency anemia is more likely to occur in children, women of childbearing age, pregnant women, and the elderly. According to the data of the World Health Organization (WHO), the global anemia rate in women is 29.9%, and the anemia rate in children is 39.8%. Iron deficiency anemia can cause a series of health problems such as reduced growth rate, poor cognitive and psychomotor development in children, decreased cognitive ability, impaired physical fitness, and decreased work ability in adults.

[0004] At present, the first-line treatment drug for iron deficiency anemia is the second-generation oral iron agent, represented by ferrous succinate, which is mainly used for the prevention and treatment of iron deficiency anemia. Ferrous succinate has very poor solubility in water and ethanol, and is almost insoluble. It dissolves in gastric acid containing dilute hydrochloric acid and can dissociate into succinate ions and ferrous ions. While participating in the tricarboxylic acid cycle and hemoglobin synthesis, it can also act on mucosal cell carriers to improve the absorption of ferrous ions; succinic acid also acts as a reducing agent to avoid the oxidation and precipitation of Fe 2+ After oral administration, ferrous succinate tablets have a high iron content and are absorbed in the duodenum and the proximal jejunum in the form of Fe 2+ to rapidly increase hemoglobin.

[0005] Compared with the first-generation oral iron agent representative, ferrous sulfate, ferrous succinate reduces the gastrointestinal side effects while improving absorption. At present, the commercially available dosage forms of ferrous succinate include ordinary tablets, granules, and sustained-release tablets. However, ferrous succinate is almost insoluble in water, and the above-mentioned preparations do not directly improve its solubility in water.

[0006] At present, the newly disclosed dosage forms of ferrous succinate mainly include the following content:

[0007] Patent CN1732911A discloses a ferrous succinate sustained-release preparation and its preparation method. Using hydroxypropyl cellulose or ethyl cellulose as the sustained-release matrix carrier, ferrous succinate is encapsulated under the action of a binder, and then granulated by the conventional method. The carrier used in this disclosed method is a polymer material carrier, which needs to disintegrate or swell before drug release, and only achieves physical combination by the action of the binder, so it is not firm, and it is only a micron-level mixture. This preparation method only improves the residence time in the stomach to achieve the purpose of improving dilution compared with ordinary tablets, and does not fundamentally improve the solubility of ferrous succinate. In addition, organic reagents such as ethanol are introduced during the preparation of this sustained-release dosage form, which is likely to cause organic solvent residues and gastrointestinal irritation.

[0008] Patent CN101102762A discloses an iron-containing composition, which is prepared by wet granulation using vitamin C or a similar iron absorbent and an excipient as the carrier material. This product improves the absorption of the drug by utilizing the material properties of the iron absorption promoter in the prescription, and does not solve its fundamental problem of poor solubility from the preparation method. In addition, a plasticizer containing organic reagents is introduced, and the iron absorption promoters used are all well-known excipients, which have nothing to do with the improvement of pharmaceutics.

[0009] Patent CN101820767A discloses an iron-containing composition and its preparation method. In this patent, skimmed milk powder containing casein is simply physically stirred with ferric chloride and then neutralized and solidified with an alkali to form micelles. This patent uses protein as the carrier, which is an iron absorption promoter, and achieves the effect of promoting absorption. However, it does not achieve the effect of reducing the particle size of micelles to improve the absorption pathway. Its action mechanism is similar to that of the insoluble matrix, and the principle is still only to utilize the simple mechanism of protein promoting iron absorption, and the drug loading is not high.

[0010] Patent CN113456617A discloses a ferrous succinate orally disintegrating film and its preparation method. In this patent, ferrous succinate, a film-forming agent, and a plasticizer are dispersed in water and stirred to form a viscous liquid to prepare the film agent. Theoretically, this dosage form can be absorbed sublingually, avoiding the first-pass effect and improving the bioavailability. However, the solubility of ferrous succinate in oral mucus (neutral) is very low, and micron-sized drugs are difficult to directly penetrate the oral mucosa and enter the blood directly. Most of the ferrous succinate still needs to dissociate under the acidic conditions of gastric acid before it can better enter. Therefore, the sublingual absorption rate of the orally disintegrating film will not be very high. Most of it is still dissociated and absorbed along with saliva and the gastrointestinal tract. The absorption individual differences are large, and it is impossible to stably supply large doses of iron supplements for various populations.

[0011] In summary, in the existing technologies, there is no method that can simultaneously improve the solubility and dispersibility of ferrous succinate in order to increase the absorption in the body and further improve the bioavailability.

[0012] In the existing traditional ferrous succinate preparation prescriptions, the excipients account for a large proportion, the absolute amount of the active pharmaceutical ingredient (API) is relatively low, the particle size of the raw material is relatively large, and poor absorption requires multiple large doses to achieve the therapeutic effect. For some elderly and young children with difficulty in swallowing and poor compliance in drug administration, the drug administration burden is increased. Therefore, it is urgent to solve the above disadvantages through new nano-formulation means. Summary of the Invention

[0013] The purpose of the present invention is to provide a ferrous succinate nano-suspension, which greatly reduces the particle size of ferrous succinate to increase the solubility and dispersibility of ferrous succinate. Through the stable ferrous succinate nano-suspension as a drug intermediate, it can be further prepared into different dosage forms such as oral suspension preparations and dry suspension preparations, in order to achieve the purpose of increasing absorption in the body, further improving the bioavailability, and improving the compliance of patients.

[0014] To achieve the purpose of the present invention, the technical solution is as follows:

[0015] A ferrous succinate nano-suspension, comprising ferrous succinate and a stabilizer; wherein, the mass ratio of ferrous succinate to the stabilizer is 1:1 to 1:10; the ferrous succinate nano-suspension is prepared by stirring ferrous succinate and the stabilizer in water and dispersing under high-energy shearing conditions followed by high-pressure homogenization.

[0016] Furthermore, the stabilizer is selected from one or more of succinic acid, mannitol, carrageenan, polyvinylpyrrolidone, polyoxyethylene sorbitan fatty acid ester Tween, polyoxyethylene hydrogenated castor oil RH, polyoxyethylene castor oil EL, lithium polyglycol dodecahydroxystearate HS15. Even further, the stabilizer is selected from one or more of mannitol, carrageenan, succinic acid. When selected from multiple stabilizers, the mass ratio of mannitol, carrageenan, and succinic acid is (16 - 8):1:2, and the mass ratio of carrageenan to succinic acid is 1:1 to 1:5.

[0017] The stabilizers selected in the present invention can be divided into two categories: one is suspending agents represented by polyvinylpyrrolidone, carrageenan, mannitol, and succinic acid, which maintain the metastable structure after dispersion through steric hindrance and viscosity; the other is solubilizers represented by non-ionic surfactants, such as Tween, polyoxyethylene castor oil EL, polyoxyethylene hydrogenated castor oil RH, etc., which achieve solubilization and dispersion by increasing wettability and forming micelles. After the stabilizer is dissolved in water, it can improve the wettability of ferrous succinate, enabling ferrous succinate to fully contact and disperse with the solution.

[0018] In a preferred embodiment, the particle size of the ferrous succinate nano-suspension is 200 - 500 nm, and the absolute value of the Zeta potential is 10 - 30 mV. More preferably, the particle size of the ferrous succinate nano-suspension is 200 - 300 nm, and the absolute value of the Zeta potential is 25 ± 5 mV.

[0019] Furthermore, the ferrous succinate nano-suspension provided by the present invention is prepared by stirring ferrous succinate and a stabilizer in water, dispersing under high-energy shearing conditions, and then performing high-pressure homogenization. The dispersion speed is 1000 - 2500 rpm, and the high-pressure homogenization pressure is 500 - 800 bar.

[0020] The present invention also provides a method for preparing a ferrous succinate nano-suspension, comprising the following steps:

[0021] S1. Take a stabilizer with a weight equivalent to 1 - 10 times that of ferrous succinate in a container, and add it to water and stir.

[0022] S2. Under the protection of an inert gas, add ferrous succinate to the solution obtained in step S1, control the temperature at 20 - 50 °C, and stir and disperse for 5 - 10 min; then, use a high-pressure homogenizer and circulate 3 - 5 times to obtain the ferrous succinate nano-suspension; the inert gas is selected from nitrogen or helium.

[0023] Furthermore, in step S2, the stirring and dispersing speed is 1000 - 2500 rpm, and the temperature does not exceed 20 - 40 °C. The machine used is a disperser, such as a turbine stirrer, a high-speed disperser, a tissue homogenizer, etc., to achieve the stirring and shearing function.

[0024] Furthermore, in step S2, the stirring and dispersing speed is 1000 - 2500 rpm, and the temperature exceeds 20 - 40 °C.

[0025] Furthermore, in step S2, the pressure of the high-pressure homogenizer is 500 - 800 bar, and the temperature does not exceed 40 °C.

[0026] Selecting to perform the operation of step 2 under the protection of an inert gas (nitrogen or helium) is because Fe in ferrous succinate 2+ is easily oxidized by oxygen in the air to Fe 3+ , resulting in a decrease in oral bioavailability.

[0027] Use of the ferrous succinate nano-suspension as described above in the preparation of a medicament for treating iron deficiency anemia.

[0028] A ferrous succinate liquid suspension preparation, comprising a ferrous succinate nano-suspension as described above and pharmaceutical excipients; the pharmaceutical excipients are selected from flavoring agents. Preferably, the flavoring agent can be selected from one or more of sucralose, sodium saccharin, and mannitol.

[0029] A dry suspension preparation of ferrous succinate, comprising a ferrous succinate nano-suspension as described above and pharmaceutical excipients; the pharmaceutical excipients are selected from one or more of mannitol, polyvinylpyrrolidone, starch, sodium carboxymethylcellulose, hydroxypropyl methylcellulose, talc, magnesium stearate, and flavoring agents. To prepare the dry suspension preparation, the above-mentioned ferrous succinate nano-suspension is mixed with the drug excipients and then dried and pulverized. The drying method can be selected from one or more of freeze-drying, spray-drying, and fluidized bed drying.

[0030] As mentioned above, the pharmaceutical excipients can be added according to the prescription dosage, and no specific limitation is made here.

[0031] In the present invention, a small amount of stabilizer is used to replace a large amount of diluents (i.e., excipients) in traditional solid preparations. While reducing the amount of excipients, the proportion and absolute amount of ferrous succinate in the preparation prescription are increased. A nano-suspension of ferrous succinate is formed by the action of high-energy shearing and homogenization cavitation force between ferrous succinate and the stabilizer. At the same time, relying on the solubilization, suspending, and steric hindrance effects of the safe, non-toxic, and biocompatible stabilizer, a stable suspension system is formed, improving the solubility and dispersibility of ferrous succinate in water. Subsequently, by means of drying for solidifying the liquid preparation, a stable and uniform ferrous succinate nano-suspension preparation can be prepared, improving the solubility and bioavailability of the drug, improving the therapeutic effect, reducing the drug dosage, enhancing the water solubility of the drug, and solving the problems of difficult absorption, low bioavailability, and poor administration compliance of traditional ferrous succinate preparations.

[0032] Compared with the prior art, the significant advantages of the present invention at least include one of the following aspects:

[0033] 1. The ferrous succinate nano-suspension synthesized in the present invention enables ferrous succinate and the stabilizer to fully contact to form nano-scale particles through the action of high-energy shearing and homogenization cavitation force. According to the Noyes-Whitney equation, the reduction of the particle size of ferrous succinate will greatly increase its solubility. Moreover, the stabilizer is not only a carrier for solubilizing and uniformly dispersing the drug but also can improve the stability of the system by relying on its own steric hindrance and suspending effects, improving the wettability, dispersibility, and biofilm permeability of ferrous succinate. And theoretically, the nano-suspension has low excipient dosage and high drug loading, solving the problem that the proportion of excipients in the traditional ferrous succinate preparation prescription is huge and the absolute amount of the active pharmaceutical ingredient (API) is relatively low.

[0034] 2. Compared with traditional sustained-release dosage forms and iron promoter compositions, the nano-suspension prepared by the present invention has high dilution stability, can be rapidly dispersed in the gastrointestinal tract, greatly increases the contact area between the drug and the absorption sites, and the nano-scale drug can rapidly penetrate the gastrointestinal mucosa and be absorbed into the blood, improving the bioavailability of the drug. In contrast, traditional liquid suspensions have drug dispersions with particle sizes above ten to hundreds of micrometers, low drug loading capacity, rapid sedimentation, large amounts of dispersants used, and some even use organic solvents, which will further stimulate the gastrointestinal tract. The stabilizers selected in the present invention are all pharmaceutically excipients that are safe, non-toxic, and have high biocompatibility as listed in domestic and foreign pharmacopoeias. While greatly increasing the solubility of the drug, the wrapping effect of the stabilizer can also avoid direct stimulation of the gastrointestinal tract and improve the absorption of ferrous succinate;

[0035] 3. The ferrous succinate nano-suspension provided by the present invention can further be mixed with a safe and inexpensive suspending agent and excipient, solidified, and freeze-dried, which can not only improve the water dispersibility of the drug but also greatly improve the storage stability of the drug;

[0036] 4. Compared with traditional liquid suspensions, the nano-liquid suspension preparation prepared according to the present invention can be administered after being dispersed in water or swallowed together with liquid food, improving the drug administration compliance of children and the elderly. While having a high drug loading capacity, it also avoids the disadvantages of traditional liquid suspensions such as low wettability, rapid sedimentation, poor dispersion, and weak storage stability;

[0037] 5. The preparation process of the nano-suspension of the composite prepared by the present invention is simple, suitable for large-scale industrial production, and has high oral compliance, meeting the oral drug administration needs of all age groups, especially taking care of children and the elderly. Detailed Embodiments

[0038] The technical solutions of the present invention will be described in detail below in combination with specific embodiments. However, the protection scope of the present invention is not limited to the following embodiments. Technical solutions obtained by those skilled in the art by changing the parameters of the present technical solution all fall within the protection scope of the present invention, which can be understood by those skilled in the art.

[0039] In the specific embodiments of the present invention, unless otherwise specified, the experimental methods involved are all conventional experimental methods in the art; unless otherwise specified, the reagents used to complete the following embodiments can all be purchased from commercial channels.

[0040] Example 1 Preparation of Ferrous Succinate Nano-Suspension 1

[0041] Ferrous succinate 1.0 g

[0042] Carrageenan 1.0 g

[0043]

Preparation

[0044] S1. Take 1.0 g of carrageenan in a beaker, add 200 ml of pure water, and stir until uniform.

[0045] S2. Under nitrogen protection, add 1.0 g of ferrous succinate, control the water bath temperature at 20 - 50 °C, use a high-speed disperser at 2500 rpm for 5 min; then circulate the obtained liquid 5 times under the pressure of 500 bar in a high-pressure homogenizer, control the temperature not exceeding 40 °C until it becomes transparent or milky, thus obtaining ferrous succinate nano-suspension 1.

[0046] Example 2 Preparation of ferrous succinate nano-suspension 2

[0047] Ferrous succinate 1.0 g

[0048] Tween80 2.0 g

[0049]

Preparation

[0050] S1. Take 2.0 g of Tween80 in a beaker, add 200 ml of pure water, and stir until clear.

[0051] S2. Under nitrogen protection, add 1.0 g of ferrous succinate, control the water bath temperature at 20 - 50 °C, use a high-speed disperser at 1000 rpm for 15 min; then circulate the obtained liquid 4 times under the pressure of 600 bar in a high-pressure homogenizer, control the temperature not exceeding 40 °C until it becomes transparent or milky, thus obtaining ferrous succinate nano-suspension 2.

[0052] Example 3 Preparation of ferrous succinate nano-suspension 3

[0053] Ferrous succinate 1.0 g

[0054] HS15 2.0 g

[0055]

Preparation

[0056] S1. Take 2.0 g of HS15 in a beaker, add 200 ml of pure water, and stir until clear.

[0057] S2. Under nitrogen protection, add 1.0 g of ferrous succinate, control the water bath temperature at 20 - 50 °C, use a high-speed disperser at 1000 rpm for 5 min; then circulate the obtained liquid 3 times under the pressure of 700 bar in a high-pressure homogenizer, control the temperature not exceeding 40 °C until it becomes transparent or milky, thus obtaining ferrous succinate nano-suspension 3.

[0058] Example 4 Preparation of ferrous succinate nano-suspension 4

[0059] Ferrous succinate 1.0 g

[0060] Carrageenan 1.0 g

[0061] Succinic acid 1.0 g

[0062]

Preparation

[0063] S1. Take 1.0 g of carrageenan and 1.0 g of succinic acid in a beaker, add 200 ml of pure water, and stir until uniform.

[0064] S2. Under the protection of inert gas nitrogen, add 1.0 g of ferrous succinate, control the water bath temperature at 20 - 50 °C, use a high-speed disperser at 1000 rpm for 5 min; then circulate the obtained liquid 3 times under the pressure of 800 bar in a high-pressure homogenizer, control the temperature not exceeding 40 °C until it becomes transparent or milky, and thus obtain the ferrous succinate nano-suspension.

[0065] Preparation of Ferrous Succinate Nano-suspension 5 in Example 5

[0066]

[0067]

Preparation

[0068] S1. Take 0.5 g of carrageenan, 1.0 g of succinic acid and 8.0 g of mannitol in a beaker, add 200 ml of pure water, and stir until uniform.

[0069] S2. Under the protection of inert gas nitrogen, add 1.0 g of ferrous succinate, control the water bath temperature at 40 °C, use a high-speed disperser at 2000 rpm for 5 min; then circulate the obtained liquid 5 times under the pressure of 500 bar in a high-pressure homogenizer, control the temperature not exceeding 40 °C until it becomes transparent or milky, and thus obtain the ferrous succinate nano-suspension 5.

[0070] Comparative Example 1

[0071] Ferrous succinate 1.0 g

[0072] Span 80 1.0 g

[0073] Mannitol 2.0 g

[0074]

Preparation

[0075] S1. Take 1.0 g of Span 80 and 2.0 g of mannitol in a beaker, add 200 ml of pure water, and stir until uniform.

[0076] S2. Under the protection of nitrogen, add 1.0 g of ferrous succinate, control the water bath temperature at 40 °C, use a high-speed disperser at 2000 rpm for 5 min; then circulate the obtained liquid 3 times under the pressure of 800 bar in a high-pressure homogenizer, control the temperature not exceeding 40 °C until it becomes transparent or milky, and thus obtain the comparative ferrous succinate nano-suspension 1.

[0077] Comparative Example 2

[0078] Ferrous succinate 1.0g

[0079] Hydroxypropyl methylcellulose 1.0g

[0080] Microcrystalline cellulose 1.0g

[0081]

preparation

[0082] S1. Take 1.0g hydroxypropyl methylcellulose and 1.0g microcrystalline cellulose in a beaker, add 200ml pure water, and stir until uniform.

[0083] S2. Under nitrogen protection, 1.0 g of ferrous succinate was added, the water bath temperature was controlled at 40° C., and a high-speed disperser was used at 2000 rpm for 5 min; the resulting liquid was then circulated 3 times in a high-pressure homogenizer at a pressure of 800 bar, with the temperature controlled not to exceed 40° C., until it became transparent or milky, to obtain a comparative ferrous succinate nanosuspension 2.

[0084] Example 6 Investigation of Sedimentation Volume Ratio

[0085] Experimental method: Use a stoppered measuring cylinder to measure 50 ml of the test sample ferrous succinate nanosuspension (Example 1: 5 mg / ml); ferrous succinate raw material drug aqueous solution (250 mg raw material drug mixed with 50 ml water); marketed ferrous succinate granules Sulifei (single bag specification contains 0.1 g ferrous succinate, 2.5 bags are dissolved in 50 ml water), seal, shake vigorously for 1 min, record the starting height H0 of the suspension, let it stand for 3 hours, record the final height H of the suspension, and calculate according to the following formula: sedimentation volume ratio = H / H0. Specific results are shown in Table 1:

[0086] Table 1: Comparison of sedimentation volume ratios of different ferrous succinate preparations

[0087] Sample Name Sedimentation Volume Ratio Ferrous Succinate Nanoparticle Suspension 0.90 Commercially Available Ferrous Succinate Granules 0.35 Aqueous Solution of Ferrous Succinate Raw Material 0.20

[0088] According to the data in Table 1, the ferrous succinate nanosuspension obtained by the preparation method of the present invention can meet the requirements of the suspension specified in the pharmacopoeia, and the ferrous succinate nanosuspension has good stability.

[0089] Example 7 Particle size distribution and investigation

[0090] Experimental method: The particle size of the ferrous succinate nanosuspensions 1-5 obtained in Examples 1-5 was measured using a Brookhaven nanoparticle sizer, and the measurement was repeated three times. The experimental results were processed using the system's own software. The experimental results are shown in Table 2. The average particle size of the prepared nanosuspensions ranged from 200 to 500 nm, the PDI was between 0.2 and 0.4, and the absolute value of the Zeta potential was between 10 and 30 mV.

[0091] Table 2: Comparison of volume ratio and particle size of ferrous succinate nano-suspensions formed with different stabilizers

[0092]

[0093] Preparation of Nano-suspension Liquid Suspension 1 in Example 8

[0094] 500 ml of ferrous succinate nano-suspension 5

[0095] 50 mg of sodium saccharin

[0096]

Preparation

[0097] Take 500 ml of ferrous succinate nano-suspension 5 (prepared in Example 5), add 50 mg of sodium saccharin, fill it into a vial at 300 rpm for 10 min to obtain the product.

[0098] Preparation of Dry Suspension 1 in Example 9

[0099] 500 ml of ferrous succinate nano-suspension 5

[0100] 5 g of sodium carboxymethylcellulose

[0101] 2 g of mannitol

[0102] 50 mg of sodium saccharin

[0103]

Preparation

[0104] Take 50 g of hypromellose and 5 g of sodium carboxymethylcellulose, respectively crush them through a 100-mesh sieve, use the equal increment method to mix 500 ml of ferrous succinate nano-suspension 5 (prepared in Example 5) with 5 g of sodium carboxymethylcellulose and 2 g of mannitol and stir evenly, then add the flavoring agent (50 mg of sodium saccharin), mix evenly, and obtain the product after freeze-drying and crushing.

[0105] Preparation of Dry Suspension 2 in Example 10

[0106]

[0107]

Preparation

[0108] Take the prescribed amounts of hypromellose and sodium carboxymethylcellulose, respectively crush them through a 100-mesh sieve, use the equal increment method to mix the nano-suspension (prepared in Example 5) with povidone, starch and the prescribed amount of mannitol and stir evenly, then add the prescribed amounts of talc, magnesium stearate and flavoring agent, mix evenly, and obtain the product after spray-drying and crushing.

[0109] Investigation on Particle Size Comparison of Solution before Drying and Reconstituted Solution of Dry Suspension in Example 11

[0110] Experimental method: Brookhaven nanoparticle size analyzer was used to examine the particle size of the ferrous succinate dry suspension prepared in Example 9 before freeze drying and after freeze drying and reconstitution. The details are as follows:

[0111] According to the preparation method of Example 9, the ferrous succinate nanosuspension 5 was mixed and stirred evenly with the medical excipients, and measured with a BrookHaven nanoparticle sizer. At the same time, the freeze-dried dry suspension 1 prepared in Example 9 was dissolved in 500 ml of water and measured with a BrookHaven nanoparticle sizer. The parallel determination was performed three times, and the experimental results were processed with the system's own software. The experimental results are shown in Table 3. The average particle size of the prepared emulsion ranged from 200 to 500 nm, and the Zeta potential was between -5 and -30 mV.

[0112] Table 3: Comparison of particle size of dry suspension before drying and after reconstitution

[0113] Status Sedimentation Volume Ratio Particle Size PDI Zata Potential Before Drying 0.93 236nm 0.220 -30mV After Reconstitution 0.90 266nm 0.235 -28mV

Claims

1. A ferrous succinate nano-suspension, characterized in that: The ferrous succinate nano-suspension comprises ferrous succinate and a stabilizer; wherein, the mass ratio of ferrous succinate to the stabilizer is 1:1 to 1:10; the ferrous succinate nano-suspension is prepared by stirring ferrous succinate and the stabilizer in water, dispersing under high-energy shearing conditions, and then performing high-pressure homogenization.

2. The ferrous succinate nano-suspension according to claim 1, characterized in that: The stabilizer is selected from one or more of succinic acid, mannitol, carrageenan, polyvinylpyrrolidone, polyoxyethylene sorbitan fatty acid ester Tween, polyoxyethylene hydrogenated castor oil RH, polyoxyethylene castor oil EL, and lithium polyglycol hydroxystearate HS15.

3. The ferrous succinate nano-suspension according to claim 1, characterized in that: The ferrous succinate nano-suspension has a particle size of 100 to 500 nm and an absolute value of Zeta potential of 5 to 40 mV.

4. The ferrous succinate nano-suspension according to claim 1, characterized in that: For the preparation of the ferrous succinate nano-suspension, the stirring and dispersion speed of ferrous succinate and the stabilizer in water is 1000 to 2500 rpm, and the high-pressure homogenization pressure thereafter is 500 to 800 bar.

5. A preparation method of the ferrous succinate nano-suspension according to claim 1, characterized in that: It includes the following steps: S1. Take a stabilizer with a weight 1 to 10 times that of ferrous succinate in a container, add it to water and stir. S2. Under the protection of an inert gas, add ferrous succinate to the solution obtained in step S1, control the temperature at 20 to 50 °C, stir and disperse for 5 to 10 min; then, use a high-pressure homogenizer and circulate 3 - 5 times to obtain the ferrous succinate nano-suspension; the inert gas is selected from nitrogen or helium.

6. The preparation method of the ferrous succinate nano-suspension according to claim 5, characterized in that: In step S2, the stirring and dispersion speed is 1000 to 2500 rpm and the temperature is 20 to 40 °C.

7. The preparation method of the ferrous succinate nano-suspension according to claim 5, characterized in that: In step S2, the pressure of the high-pressure homogenizer is 500 to 800 bar and the temperature does not exceed 40 °C.

8. Use of the ferrous succinate nano-suspension according to any one of claims 1-4 in the preparation of a medicament for treating iron deficiency anemia.

9. A ferrous succinate liquid suspension preparation, characterized in that: It contains a ferrous succinate nano-suspension as described in any one of claims 1 - 4 and a pharmaceutical excipient; the pharmaceutical excipient is selected from flavoring agents.

10. A ferrous succinate dry suspension preparation, characterized in that: It contains a ferrous succinate nano-suspension as described in any one of claims 1 - 4 and a pharmaceutical excipient; the pharmaceutical excipient is selected from one or more of mannitol, polyvinylpyrrolidone, starch, sodium carboxymethylcellulose, hydroxypropyl methylcellulose, talc, magnesium stearate, and flavoring agents.

Images