A method for preparing and use of a vaginal progesterone sustained-release gel

Abstract

The present application provides a preparation method and application of a vaginal administration progesterone sustained-release gel. In one aspect, the gel matrix is a combination of sodium alginate and polycarbophil, and the ratio of the two is 2.6:1, which has the highest in-vitro dissolution release rate. In another aspect, the optimal process for preparing the progesterone sustained-release gel is that the particle size of progesterone micronized powder is 15 μm, the ratio of the progesterone raw powder and the gel matrix (sodium alginate + polycarbophil) is 5:6, and the mixing temperature of the C water phase gel and the C phase is 40 DEG C, so that the progesterone sustained-release gel obtained has the highest in-vitro dissolution rate and the highest bioavailability.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical preparations, specifically relating to a method for preparing and applying a vaginal progesterone sustained-release gel. Background Technology

[0002] Progesterone is an important component in regulating the female reproductive system. Its main physiological function is to identify and maintain pregnancy in animals. It acts primarily on the uterine muscle and endometrium, and plays a supporting role in implantation of the fertilized egg. Progesterone is an essential hormone for maintaining pregnancy. Progesterone works in conjunction with estrogen to regulate various changes during the reproductive cycle.

[0003] Progesterone is widely used in gynecological diseases, especially in hormone replacement therapy (HRT) when used in combination with estrogen to effectively avoid the adverse reactions associated with estrogen. Common administration methods for progesterone include oral, injectable, and vaginal administration. However, natural progesterone has poor oral absorption and a strong first-pass effect. Intramuscular injection of progesterone has also been used for a long time, as it is absorbed more completely and is relatively inexpensive. However, it requires a hospital visit and is invasive. Oily preparations are the most common form and can cause adverse reactions such as redness, swelling, itching, and hardening at the injection site. Prolonged use can lead to abscesses at the injection site, which typically take several weeks to recover from, causing inconvenience to the patient.

[0004] Compared to other drug delivery systems, vaginal delivery systems offer several advantages, such as the ability of drugs absorbed through the vagina to exert both local and systemic therapeutic effects, and high bioavailability. Vaginal administration of progesterone has been used for a considerable period due to its convenience, self-administration by patients, non-invasive nature, direct targeting, and enhanced absorption. However, current preparations of vaginal progesterone formulations often encounter issues such as raw material aggregation, failure to disperse, or aggregation and fusion during cooling and storage, which negatively impact absorption and bioavailability. Therefore, improving the bioavailability of progesterone has become a crucial issue in its application. Summary of the Invention

[0005] In view of the shortcomings of the prior art, the purpose of this invention is to provide a method for preparing and applying a vaginal progesterone sustained-release gel.

[0006] To achieve this objective, the present invention adopts the following technical solution:

[0007] First, the present invention provides a method for preparing a vaginal progesterone sustained-release gel, comprising the following steps:

[0008] S1. Weigh out polycarbofil by weight, add 0.5-2 times the amount of deionized water to soak for 6-12 hours, stir thoroughly until it is completely swollen into a uniform polymer, and obtain phase A for later use.

[0009] S2. Weigh out sorbic acid by weight and place it in a container. Add 1.5-5.5 times the amount of deionized water for the sorbic acid and sonicate for 5-12 minutes. Then slowly add sodium alginate in small amounts multiple times while stirring constantly until the mixture is homogeneous to obtain phase B.

[0010] S3. Heat at 45-65℃, and slowly add phase B to phase A while stirring. Continue stirring until a homogeneous aqueous gel is formed. Set aside.

[0011] S4. Weigh out glycerol, liquid paraffin, and glyceryl behenate according to the weight parts, heat them at 35-42℃ to melt them, stir them thoroughly to obtain phase C, and set aside for later use;

[0012] S5. Weigh the coarse progesterone raw material according to the weight parts, and perform ultrafine pulverization to obtain progesterone micro powder with a particle size of 10-30μm, for later use;

[0013] S6. After heating both the aqueous phase gel and the C phase to 40-55℃, the two phases are mixed and stirred continuously until homogeneous. Then, progesterone micro powder is added in small amounts several times while stirring until homogeneous. Triethanolamine is added to adjust the pH value to 3.5-5.5 to obtain the progesterone sustained-release gel.

[0014] Furthermore, the range of the raw material dosage is as follows: 10-20 parts of crude progesterone powder, 0.5-5 parts of polycarboxylic acid, 2-10 parts of sodium alginate, 0.1-1 parts of sorbic acid, 2-6 parts of glycerol, 1-3 parts of liquid paraffin, and 0.2-1.5 parts of behenic acid glyceride.

[0015] Furthermore, the ratio of sodium alginate to polycarbamide is 2:1 to 3.2:1;

[0016] Furthermore, the ratio of sodium alginate to polycarbamide is 2.6:1.

[0017] Furthermore, in step S1, the amount of deionized water used is 1.5 times the normal volume, and the soaking time is 10 hours.

[0018] Furthermore, in step S2, the amount of deionized water used is 4 times the normal amount, and the ultrasonic dissolution time is 8 minutes.

[0019] Furthermore, the heating temperature in step S3 is 55°C, and the heating temperature in step S4 is 40°C;

[0020] Furthermore, in step S5, the particle size of the progesterone micropowder is 15 μm;

[0021] Furthermore, in step S6, the mixing temperature of the aqueous gel and the C phase is 40°C, and the pH value is adjusted to 4.5.

[0022] Secondly, the present invention provides the application of the progesterone sustained-release gel in the preparation of progesterone supplements for assisted reproduction.

[0023] The beneficial effects of this invention are as follows:

[0024] (1) By screening commonly used sustained-release gel matrix raw materials, the inventors found that using sodium alginate and polycarbamide in combination not only resulted in stable release but also the highest release rate, reaching approximately 95.5% after 24 hours of release. Based on this, the optimal ratio of the two was screened, and it was found that when the ratio of the two was 2.6:1, the in vitro dissolution release rate was the highest, reaching approximately 96.6%, and the release was stable.

[0025] (2) After determining the ratio of sodium alginate to polycarboxylic acid, the inventors screened the optimal process for preparing progesterone sustained-release gel and found that the optimal preparation process was as follows: the particle size of progesterone micro powder was 15 μm, the ratio of progesterone raw material coarse powder to gel matrix (sodium alginate + polycarboxylic acid) was 5:6, and the mixing temperature of C aqueous phase gel and C phase was 40℃. The progesterone sustained-release gel obtained had the highest in vitro dissolution rate and the highest bioavailability.

[0026] (3) The progesterone sustained-release gel prepared by the present invention is not only simple and easy to operate, suitable for industrial production, but also has safe and non-toxic raw materials with high stability and release rate and high bioavailability. It can achieve continuous drug release after vaginal administration and is suitable for women to supplement progesterone. Attached Figure Description

[0027] Figure 1 The effect of different matrix raw materials on the in vitro dissolution and release rate of progesterone sustained-release gel;

[0028] Figure 2 The effect of the ratio of sodium alginate to polycarbomer on the in vitro dissolution and release rate of progesterone sustained-release gel was investigated. Detailed Implementation

[0029] To better understand the present invention, the embodiments of the present invention will be described in detail below with reference to the examples. However, those skilled in the art will understand that the following examples are only for illustrating the present invention and should not be regarded as limiting the scope of the present invention.

[0030] Experimental Example 1: Screening of Gel Matrix

[0031] Based on experience, commonly used gel matrices for preparing gel formulations were selected: poloxamer 407, sodium alginate, polycarbamide, and chitosan. These four raw materials were combined in pairs, and their in vitro dissolution and release rates were determined to identify the optimal matrix combination. First, poloxamer 407, sodium alginate, polycarbamide, and chitosan were combined to obtain groups 1-6, namely: poloxamer 407 + sodium alginate, poloxamer 407 + polycarbamide, poloxamer 407 + chitosan, sodium alginate + polycarbamide, sodium alginate + chitosan, and polycarbamide + chitosan.

[0032] The preparation method for Group 1 is as follows: Weigh 4g of poloxamer 407, add 6g of deionized water and soak for 8 hours, stirring thoroughly until completely swollen into a homogeneous polymer to obtain phase A; Place 0.8g of sorbic acid in a container, add 2.4g of deionized water, sonicate for 5 minutes, then slowly add 10g of sodium alginate in small amounts several times, stirring constantly until uniformly mixed to obtain phase B; Heat at 50℃, while stirring, slowly add phase B to phase A, and continue stirring until a homogeneous aqueous gel is formed. Weigh 5g of glycerol, 2.5g of liquid paraffin, and 1.3g of behenicol ester, heat at 36℃ to melt, and stir thoroughly to obtain phase C. Weigh 15g of coarse progesterone raw material powder, and perform ultrafine pulverization to obtain progesterone micro-powder with a particle size of 20μm. Heat both the aqueous gel and phase C to 45℃, mix the two phases, and stir continuously until homogeneous. Then, add progesterone micro-powder in small amounts several times while stirring until homogeneous. Add triethanolamine to adjust the pH to 3.5 to obtain the progesterone sustained-release gel. When preparing sustained-release gels in groups 2-6, replace poloxamer 407 and sodium alginate with the combinations in groups 2-6, respectively. The remaining methods and dosage parameters are the same as those in group 1. After obtaining the progesterone sustained-release gels prepared in groups 1-6, determine their in vitro dissolution and release rates within 24 hours. The in vitro dissolution and release rate was determined as follows: High-performance liquid chromatography (HPLC) was used to determine the drug concentration and calculate the dissolution rate. Referring to relevant documents published by the FDA, the in vitro dissolution of progesterone vaginal sustained-release gel was performed using the first method (basket method) from the Pharmacopoeia. The dissolution medium was 1000 mL of 20% methanol-water, the temperature was (37±1)℃, and the rotation speed was 100 rpm. 100 mg±2% of the formulation was placed in the center of a 0.45 μm microporous membrane, which was fixed to the bottom of the rotating basket. Samples were taken at 0 h, 2 h, 4 h, 4 h, 8 h, 16 h, and 24 h. The samples were filtered through a 0.45 μm membrane, and the concentration of the dissolved sample was determined by HPLC, and the release rate was calculated. Each experiment was repeated three times. Results are shown below. Figure 1 .

[0033] according to Figure 1 The results show that the progesterone sustained-release gel prepared by using sodium alginate and polycarbamide as the gel matrix has the highest in vitro release rate, reaching about 95.5%, and the release is stable.

[0034] Experimental Example 2: Screening of the dosage ratio of sodium alginate + polycarboxymethyl methacrylate

[0035] Based on the results of Experiment 1, it can be seen that the release effect is best when the gel matrix is ​​sodium alginate + polycarboxylic acid. Therefore, sodium alginate and polycarboxylic acid were selected as the gel matrix for subsequent experiments. Following the 2.5:1 ratio of sodium alginate to polycarboxylic acid in Experiment 1, the ratios were set to 2:1, 2.3:1, 2.6:1, 2.9:1, and 3.2:1. The preparation method was the same as in Experiment 1, and progesterone sustained-release gels were prepared accordingly. The in vitro dissolution rate of the progesterone sustained-release gels was determined using the same method, with each experiment repeated three times. The results are shown below. Figure 2 .

[0036] according to Figure 2 The results show that when the ratio of sodium alginate to polycarboxyfil is 2.6:1, the resulting progesterone sustained-release gel exhibits the highest in vitro release rate, reaching approximately 96.6%, and the release is stable. Therefore, 2.6:1 was chosen as the subsequent ratio of sodium alginate to polycarboxyfil.

[0037] Experiment Example 3: Screening of the optimal preparation process

[0038] As described above, based on a sodium alginate to polycarbamide ratio of 2.6:1, the optimal preparation method for progesterone sustained-release gel was screened. The specific preparation method was the same as in Experimental Example 1. Orthogonal experiments were conducted, with each experiment repeated three times, and the in vitro dissolution rate of each sustained-release gel was measured. Each experiment was repeated three times.

[0039] The orthogonal experimental design was as follows: a three-factor, four-level orthogonal experiment was conducted based on the main influencing factors of the production process, namely the particle size of the active pharmaceutical ingredient progesterone, the ratio of progesterone to the gel matrix (sodium alginate + polycarboxylic acid), and the mixing temperature of the aqueous phase gel and the C phase. The arrangement of the factor levels is shown in Table 1.

[0040] Table 1. Factor Levels of Orthogonal Experiment

[0041]

[0042] The results of the orthogonal experiment are shown in Table 2.

[0043] Table 2 Results of the orthogonal experiment

[0044]

[0045] As can be seen from Table 2, the sustained-release gel prepared in Experiment No. 13 had the highest dissolution and release rate, which was 99.1 ± 0.6%. That is, the optimal production process of the vaginal progesterone sustained-release gel of the present invention is as follows: the progesterone micro powder has a particle size of 15 μm, the ratio of progesterone raw material coarse powder to gel matrix (sodium alginate + polycarboxamide) is 5:6, and the mixing temperature of C aqueous phase gel and C phase is 40℃. The progesterone sustained-release gel obtained has the highest in vitro dissolution rate and the highest bioavailability.

[0046] In summary, the experimental results show that, on the one hand, the highest in vitro dissolution and release rate is achieved when the gel matrix is ​​a combination of sodium alginate and polycarboxylic acid in a ratio of 2.6:1. On the other hand, the optimal process for preparing the progesterone sustained-release gel is as follows: progesterone micropowder particle size of 15 μm, a ratio of progesterone raw material coarse powder to gel matrix (sodium alginate + polycarboxylic acid) of 5:6, and a C-phase aqueous gel and C-phase mixing temperature of 40℃. These conditions result in the highest in vitro dissolution rate and bioavailability of the progesterone sustained-release gel. Therefore, the progesterone sustained-release gel prepared by this invention is not only simple and easy to operate, suitable for industrial production, but also uses safe and non-toxic raw materials with high stability, high release rate, and high bioavailability. This allows for sustained drug release after vaginal administration, making it suitable for women supplementing with progesterone.

[0047] Example 1:

[0048] A method for preparing a vaginal progesterone sustained-release gel includes the following steps:

[0049] S1. Weigh 5g of polycarboxymethyl methacrylate (PCM), add twice the amount of deionized water to soak for 12 hours, stir thoroughly until it is completely swollen into a uniform polymer, and obtain phase A for later use.

[0050] S2. Weigh 1g of sorbic acid and place it in a container. Add 5.5 times the amount of deionized water to the sorbic acid and sonicate to dissolve for 12 minutes. Then slowly add 10g of sodium alginate in small amounts several times while stirring constantly until the mixture is homogeneous to obtain phase B.

[0051] S3. Heat at 65℃, and slowly add phase B to phase A while stirring. Continue stirring until a homogeneous aqueous gel is formed. Set aside.

[0052] S4. Weigh 6g of glycerol, 3g of liquid paraffin, and 1.5g of behenicol glyceride, heat at 42℃ to melt them, stir thoroughly to obtain phase C, and set aside.

[0053] S5. Weigh 20g of coarse progesterone raw material powder, and perform ultrafine pulverization to obtain progesterone micro powder with a particle size of 30μm, for later use;

[0054] S6. After heating both the aqueous phase gel and the C phase to 50°C, the two phases are mixed and stirred continuously until homogeneous. Then, progesterone micropowder is added in small amounts several times while stirring until homogeneous. Triethanolamine is added to adjust the pH value to 5.5 to obtain the progesterone sustained-release gel.

[0055] Example 2:

[0056] A method for preparing a vaginal progesterone sustained-release gel includes the following steps:

[0057] S1. Weigh 5g of polycarboxymethyl methacrylate (PCM), add 1.5 times the amount of PCM in deionized water and soak for 8 hours. Stir thoroughly until it is completely swollen into a uniform polymer to obtain phase A.

[0058] S2. Weigh 2g of sorbic acid and place it in a container. Add 3.5 times the amount of deionized water to the sorbic acid and sonicate to dissolve for 11 minutes. Then slowly add 15g of sodium alginate in small amounts several times while stirring constantly until the mixture is homogeneous to obtain phase B.

[0059] S3. Heat at 60℃, and slowly add phase B to phase A while stirring. Continue stirring until a homogeneous aqueous gel is formed. Set aside.

[0060] S4. Weigh 25g of glycerol, 12g of liquid paraffin, and 3g of behenicol glyceride, heat them at 40℃ to melt them, stir them thoroughly to obtain phase C, and set aside.

[0061] S5. Weigh 100g of coarse progesterone raw material powder, and perform ultrafine pulverization to obtain progesterone micro powder with a particle size of 20μm, for later use;

[0062] S6. After heating both the aqueous phase gel and the C phase to 55°C, the two phases are mixed and stirred continuously until homogeneous. Then, progesterone micro powder is added in small amounts several times while stirring until homogeneous. Triethanolamine is added to adjust the pH value to 5.0 to obtain the progesterone sustained-release gel.

[0063] Example 3:

[0064] A method for preparing a vaginal progesterone sustained-release gel includes the following steps:

[0065] S1. Weigh 40g of polycarboxymethyl methacrylate (PCM), add 1.8 times the amount of PCM in deionized water and soak for 9 hours. Stir thoroughly until it is completely swollen into a homogeneous polymer to obtain phase A.

[0066] S2. Weigh 0.8g of sorbic acid and place it in a container. Add 2.8 times the amount of deionized water to the sorbic acid and sonicate to dissolve for 6 minutes. Then slowly add 70g of sodium alginate in small amounts several times while stirring constantly until the mixture is homogeneous to obtain phase B.

[0067] S3. Heat at 65℃, and slowly add phase B to phase A while stirring. Continue stirring until a homogeneous aqueous gel is formed. Set aside.

[0068] S4. Weigh 30g of glycerol, 15g of liquid paraffin, and 2g of behenicol glyceride. Heat them at 38℃ to melt them and stir thoroughly to obtain phase C. Set aside for later use.

[0069] S5. Weigh 150g of coarse progesterone raw material powder, and perform ultrafine pulverization to obtain progesterone micro powder with a particle size of 12μm, for later use;

[0070] S6. After heating both the aqueous phase gel and the C phase to 40°C, the two phases are mixed and stirred continuously until homogeneous. Then, progesterone micro powder is added in small amounts several times while stirring until homogeneous. Triethanolamine is added to adjust the pH value to 4.0 to obtain the progesterone sustained-release gel.

[0071] Example 4:

[0072] A method for preparing a vaginal progesterone sustained-release gel includes the following steps:

[0073] S1. Weigh 200g of polycarboxymethyl methacrylate (PCM), add 1.8 times the amount of PCM in deionized water and soak for 8 hours. Stir thoroughly until it is completely swollen into a uniform polymer to obtain phase A.

[0074] S2. Weigh 60g of sorbic acid and place it in a container. Add twice the amount of deionized water to the sorbic acid and sonicate to dissolve for 7 minutes. Then slowly add 600g of sodium alginate in small amounts several times while stirring constantly until the mixture is homogeneous to obtain phase B.

[0075] S3. Heat at 65℃, and slowly add phase B to phase A while stirring. Continue stirring until a homogeneous aqueous gel is formed. Set aside.

[0076] S4. Weigh 300g of glycerol, 100g of liquid paraffin, and 20g of behenicol glyceride. Heat them at 35°C to melt them and stir thoroughly to obtain phase C. Set aside for later use.

[0077] S5. Weigh 1000g of coarse progesterone raw material powder, and perform ultrafine pulverization to obtain progesterone micro powder with a particle size of 10μm, for later use;

[0078] S6. After heating both the aqueous phase gel and the C phase to 45°C, the two phases are mixed and stirred continuously until homogeneous. Then, progesterone micro powder is added in small amounts several times while stirring until homogeneous. Triethanolamine is added to adjust the pH value to 3.8 to obtain the progesterone sustained-release gel.

[0079] Example 5:

[0080] A method for preparing a vaginal progesterone sustained-release gel includes the following steps:

[0081] S1. Weigh 4g of polycarboxymethyl methacrylate (PCM), add 1.5 times the amount of PCM in deionized water and soak for 8 hours. Stir thoroughly until it is completely swollen into a uniform polymer to obtain phase A.

[0082] S2. Weigh 0.8g of sorbic acid and place it in a container. Add 3 times the amount of deionized water to the sorbic acid and sonicate for 5 minutes. Then slowly add 10g of sodium alginate in small amounts several times while stirring constantly until the mixture is homogeneous to obtain phase B.

[0083] S3. Heat at 55℃, and slowly add phase B to phase A while stirring. Continue stirring until a homogeneous aqueous gel is formed. Set aside.

[0084] S4. Weigh 5g of glycerol, 2.5g of liquid paraffin, and 1.3g of behenicol glyceride, heat at 36℃ to melt, stir thoroughly to obtain phase C, and set aside.

[0085] S5. Weigh 15g of coarse progesterone raw material powder, and perform ultrafine pulverization to obtain progesterone micro powder with a particle size of 15μm, for later use;

[0086] S6. After heating both the aqueous phase gel and the C phase to 40°C, the two phases are mixed and stirred continuously until homogeneous. Then, progesterone micropowder is added in small amounts several times while stirring until homogeneous. Triethanolamine is added to adjust the pH value to 3.5 to obtain the progesterone sustained-release gel.

[0087] Example 6:

[0088] A method for preparing a vaginal progesterone sustained-release gel includes the following steps:

[0089] S1. Weigh 10g of polycarboxymethyl methacrylate (PCM), add 1.5 times the amount of deionized water to soak for 10 hours, stir thoroughly until it is completely swollen into a uniform polymer to obtain phase A, and set aside.

[0090] S2. Weigh 1g of sorbic acid and place it in a container. Add 4 times the amount of deionized water to the sorbic acid and sonicate for 8 minutes. Then slowly add 26g of sodium alginate in small amounts several times while stirring constantly until the mixture is homogeneous to obtain phase B.

[0091] S3. Heat at 55℃, and slowly add phase B to phase A while stirring. Continue stirring until a homogeneous aqueous gel is formed. Set aside.

[0092] S4. Weigh 8g of glycerol, 5g of liquid paraffin, and 2g of behenicol glyceride, heat them at 40℃ to melt them, stir them thoroughly to obtain phase C, and set aside.

[0093] S5. Weigh 30g of coarse progesterone raw material powder, and perform ultrafine pulverization to obtain progesterone micro powder with a particle size of 15μm, for later use;

[0094] S6. After heating both the aqueous gel and the C phase to 40°C, the two phases are mixed and stirred continuously until homogeneous. Then, progesterone micropowder is added in small amounts several times while stirring until homogeneous. Triethanolamine is added to adjust the pH value to 4.5 to obtain the progesterone sustained-release gel.

[0095] The applicant declares that this invention illustrates the preparation method and application of a vaginal progesterone sustained-release gel through the above embodiments, but the invention is not limited to the above embodiments, that is, it does not mean that the invention must rely on the above embodiments to be implemented. Those skilled in the art should understand that any improvements to this invention, equivalent substitutions of the raw materials of the product, addition of auxiliary components, and selection of specific methods, etc., all fall within the protection scope and disclosure scope of this invention.

[0096] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

[0097] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not describe the various possible combinations separately.

Claims

1. A method for preparing a vaginal progesterone sustained-release gel, characterized in that, Includes the following steps: S1. Weigh out polycarbofil by weight, add 0.5-2 times the amount of deionized water to soak for 6-12 hours, stir thoroughly until completely swollen into a uniform polymer, and obtain phase A for later use; S2. Weigh out sorbic acid by weight and place it in a container. Add 1.5-5.5 times the amount of deionized water for the sorbic acid and sonicate for 5-12 minutes. Then slowly add sodium alginate in small amounts several times while stirring constantly until the mixture is homogeneous to obtain phase B. S3. Heat at 45-65℃, and slowly add phase B to phase A while stirring. Continue stirring until a homogeneous aqueous gel is formed. Set aside. S4. Weigh out glycerol, liquid paraffin, and glyceryl behenate by weight, heat at 35-42℃ to melt them, stir thoroughly to obtain phase C, and set aside. S5. Weigh the coarse progesterone raw material according to the weight parts, and perform ultrafine pulverization to obtain progesterone micro powder with a particle size of 15 μm, for later use; S6. After heating both the aqueous phase gel and the C phase to 40°C, the two phases are mixed and stirred continuously until homogeneous. Then, progesterone micropowder is added in small amounts several times while stirring until homogeneous. Triethanolamine is added to adjust the pH to 4.5 to obtain the progesterone sustained-release gel. The raw material dosage range is as follows: 10-20 parts of crude progesterone powder, 0.5-5 parts of polycarboxylic acid, 2-10 parts of sodium alginate, 0.1-1 parts of sorbic acid, 2-6 parts of glycerol, 1-3 parts of liquid paraffin, and 0.2-1.5 parts of behenic acid glyceride; the dosage ratio of sodium alginate to polycarboxylic acid is 2.6:1; the dosage ratio of crude progesterone powder to gel matrix is ​​5:6, and the gel matrix is ​​sodium alginate and polycarboxylic acid.

2. The method for preparing the vaginal progesterone sustained-release gel as described in claim 1, characterized in that, In step S1, the amount of deionized water used is 1.5 times the normal volume, and the soaking time is 10 hours.

3. The method for preparing the vaginal progesterone sustained-release gel as described in claim 1, characterized in that, In step S2, the amount of deionized water used is 4 times the normal volume, and the ultrasonic dissolution time is 8 minutes.

4. The method for preparing the vaginal progesterone sustained-release gel as described in claim 1, characterized in that, The heating temperature in step S3 is 55°C, and the heating temperature in step S4 is 40°C.

5. The use of a progesterone sustained-release gel prepared by any one of claims 1-4 in the preparation of progesterone supplements for assisted reproduction.

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