A method for detecting aldehyde content in medical device products

Abstract

The present application relates to the technical field of analytical chemistry, and specifically discloses a detection method for aldehyde content in a medical device product. The detection method for aldehyde content in the medical device product provided by the present application, the steps are: the sample is placed in extracting solution A for extraction, alkaline red hydrochloride solution is added to react with sodium sulfite solution, and the free aldehyde content in the sample is determined by spectrophotometry; extracting solution A is: 0.7-1.1wt% sodium chloride, 0.2-0.8wt% saturated alkane, 1-3wt% dimethyl sulfoxide, and the solvent is water; the sample is placed in extracting solution B for extraction, alkaline red hydrochloride solution is added to react with sodium sulfite solution, and the total aldehyde content in the sample is determined by spectrophotometry; extracting solution B is: 0.4-0.6mol / L phosphoric acid, 0.1-0.3mol / L methanol, and the solvent is water. The detection method of the present application detects the aldehyde content in medical device products, with the advantages of low detection limit, high accuracy and precision.

Description

Technical Field

[0001] The present application relates to the technical field of analytical chemistry, and in particular to a method for detecting the aldehyde content in a medical device product. Background Art

[0002] As people's environmental awareness increases, governments and relevant agencies around the world are increasingly restricting the content of harmful substances such as aldehydes in products. Aldehydes have a pungent odor and are potentially harmful to human health. Long-term contact or inhalation of aldehydes may cause a series of health problems, such as irritation of the eyes and nasal mucosa, dry cough, dry and itchy skin, dizziness, nausea and other symptoms. In severe cases, it may even lead to a decrease in the body's immunity and cause a variety of diseases. The detection of aldehyde content is one of the important indicators for evaluating product quality.

[0003] At present, there are many methods for detecting aldehyde groups, mainly spectrophotometry, titration, and high performance liquid chromatography. With the application of various new technologies and people's attention to aldehyde pollution, new analytical methods such as gas chromatography, flow injection, catalytic kinetics, polarography, etc., which can greatly improve the sensitivity of aldehyde detection, are constantly being established. However, most of the existing detection methods are aimed at the detection of home furnishings and foods, and there are no relevant reports on the detection of aldehyde content in medical device products (such as collagen sponge products and decellularized products).

[0004] However, most medical device products are prepared by chemical cross-linking using aldehyde groups (such as formaldehyde, acetaldehyde, glutaraldehyde, etc.), which are easy to remain and cause cytotoxic reactions. Therefore, testing the aldehyde content in medical device products is an important measure to ensure product safety and protect consumer health; by regularly testing and controlling the aldehyde content, problems in the production process can be discovered and dealt with in a timely manner, improving product quality and stability. Summary of the invention

[0005] In order to solve the above technical problems, the present application provides a method for detecting the aldehyde content in a medical device product.

[0006] The present application provides a method for detecting the aldehyde content in a medical device product, which specifically comprises the following steps:

[0007] Place the medical device product sample in extracting solution A, stir and extract for 50-80 minutes at 30-40°C, repeat the extraction 3-5 times, combine the extracts as the sample solution A to be tested, add alkaline red hydrochloride solution and sodium sulfite solution, shake and react at room temperature, let stand for 45-55 minutes, and then use spectrophotometry and standard working curve to determine the free aldehyde content in the medical device product;

[0008] The extract A is composed of the following components: 0.7-1.1 wt% sodium chloride, 0.2-0.8 wt% saturated alkane, 1-3 wt% dimethyl sulfoxide, and the solvent is water;

[0009] Place the medical device product sample in the extracting solution B, stir and extract for 50-80 minutes at 85-95°C, add alkaline red hydrochloride solution and sodium sulfite solution as the sample solution B to be tested, shake and react at room temperature, let stand for 45-55 minutes, and then use spectrophotometry and standard working curve to determine the total aldehyde content in the medical device product;

[0010] The extract B is composed of components with the following concentrations: 0.4-0.6 mol / L phosphoric acid, 0.1-0.3 mol / L methanol, and the solvent is water.

[0011] Preferably, the extract A is composed of components with the following concentrations: 0.8-1.0 wt% sodium chloride, 0.4-0.6 wt% saturated alkane, 1.5-2.5 wt% dimethyl sulfoxide, and the solvent is water.

[0012] Preferably, in the extract A, the saturated alkane is selected from any one of n-heptane, n-hexane and petroleum ether.

[0013] Preferably, in the method for preparing the sample solution A, the stirring extraction temperature is 33-38°C.

[0014] Preferably, the extract B is composed of components with the following concentrations: 0.45-0.55 mol / L phosphoric acid, 0.15-0.25 mol / L methanol, and the solvent is water.

[0015] Preferably, in the method for preparing the sample solution B, the stirring extraction temperature is 88-93°C.

[0016] Preferably, the solid-to-liquid ratio of the medical device product sample to the extract is 45-55 mg:4.5-5.5 mL.

[0017] Preferably, the measuring point of the spectrophotometry is at 580 nm.

[0018] Preferably, the method for drawing the standard working curve of the free aldehyde content is: using extract A as a solvent, preparing a series of aldehyde-extract A solutions with concentrations of 10 μg / mL, 5 μg / mL, 2 μg / mL, 1 μg / mL, and 0.5 μg / mL as standard working solution A, and using extract A as a blank working solution, adding alkaline red hydrochloride solution and sodium sulfite solution, shaking and reacting at room temperature, standing for 45-55 minutes, and then using a spectrophotometer to measure the absorbance of standard working solution A and blank working solution A at 580 nm, and drawing a standard working curve of the free aldehyde content.

[0019] Preferably, the method for drawing the standard working curve of the total aldehyde content is: using extract B as a solvent, preparing a series of aldehyde-extract B solutions with concentrations of 10 μg / mL, 5 μg / mL, 2 μg / mL, 1 μg / mL, and 0.5 μg / mL as standard working solution B, and using extract B as blank working solution B, adding alkaline red hydrochloride solution and sodium sulfite solution, shaking and reacting at room temperature, standing for 45-55 minutes, and then using a spectrophotometer to measure the absorbance of the standard working solution and the blank working solution B at 580 nm, and drawing a standard working curve of the total aldehyde content.

[0020] Preferably, the alkaline red hydrochloride solution is an alkaline red hydrochloride aqueous solution containing 5.0-5.4 mmol / L basic red and 2.2-2.6 mol / L hydrochloric acid; the volume ratio of the alkaline red hydrochloride solution to the sample solution to be tested is 0.2-0.4:1.

[0021] Preferably, the sodium sulfite solution is an aqueous sodium sulfite solution with a concentration of 7.5-8.5 mmol / L; the volume ratio of the aqueous sodium sulfite solution to the sample solution to be tested is 0.4-0.6:1.

[0022] Preferably, the medical device product is collagen, gelatin or acellular product.

[0023] In summary, the technical solution of this application has the following effects:

[0024] The present application uses an aqueous solution containing 0.7-1.1wt% sodium chloride, 0.2-0.8wt% saturated alkane, and 1-3wt% dimethyl sulfoxide as an extracting solution A to extract free aldehyde groups from a medical device product sample, and then determine the content of free aldehyde groups in the medical device product sample; at the same time, an aqueous solution containing 0.7-1.1wt% sodium chloride, 0.2-0.8wt% saturated alkane, and 1-3wt% dimethyl sulfoxide is used as an extracting solution B to extract total aldehyde groups from the medical device product sample, and then determine the content of total aldehyde groups in the medical device product sample. The detection method detects the aldehyde content in medical device products, and has the advantages of low detection limit, high accuracy and precision. DETAILED DESCRIPTION

[0025] The present application is further described in detail below in conjunction with examples, comparative examples and performance testing experiments. These examples should not be construed as limiting the scope of protection claimed in the present application.

[0026] The alkaline red hydrochloride solution used in the examples of the present application is an alkaline red hydrochloride aqueous solution containing 5.2 mmol / L basic red and 2.4 mol / L hydrochloric acid; the sodium sulfite solution used is an aqueous sodium sulfite solution with a concentration of 8.0 mmol / L.

[0027] Example

[0028] Example 1

[0029] Example 1 provides a method for detecting the aldehyde content in a medical device product.

[0030] (1) The specific steps of the method for detecting the free aldehyde content are:

[0031] (1.1) Preparation of blank working solution A (extract solution A)

[0032] With deionized water as solvent, an aqueous solution containing 0.9 wt % sodium chloride, 0.5 wt % saturated alkane n-hexane, and 2 wt % dimethyl sulfoxide was prepared as extracting solution A, ie, blank working solution A.

[0033] (1.2) Preparation of standard working solution A and drawing of standard working curve A

[0034] Using extract A as solvent, prepare a series of aldehyde-extract A solutions with concentrations of 10 μg / mL, 5 μg / mL, 2 μg / mL, 1 μg / mL, and 0.5 μg / mL as standard working solution A, and use extract A as blank working solution. Take 1.0 mL of standard working solution and 1.0 mL of blank working solution in test tubes, add 0.30 mL of alkaline red hydrochloride solution and shake and mix, add 0.50 mL of sodium sulfite and shake and mix, let stand for 50 minutes, and then use a spectrophotometer to measure the absorbance of standard working solution A and blank working solution A at 580 nm, and use aldehyde concentration as the horizontal axis and absorbance value as the vertical axis to draw the standard working curve A of free aldehyde content.

[0035] (1.3) Preparation of sample solution A and detection of free aldehyde content

[0036] In triplicate, accurately weigh approximately 50 mg of collagen sponge (approximately 15 mm x 15 mm product), record the exact weight, and transfer it to a polypropylene screw-top glass bottle.

[0037] Add 5 mL of extracting solution A to the collagen sponge bottle, cover tightly, and place on an orbital shaker. Place the vial on one side of the orbital shaker, adjust the orbital shaker speed to 100 rpm, and stir and extract for 60 minutes at 35°C. Then transfer the solution from the sponge vial to a new label bottle, and add 5 mL of extracting solution A to the sponge vial. Repeat the extraction 4 times in total, and combine the extracts as the sample solution A to be tested. Take 1.0 mL of the sample solution A to be tested in a test tube, add 0.30 mL of alkaline red hydrochloride solution and shake to mix, add 0.50 mL of sodium sulfite and shake to mix, let stand for 50 minutes, and then use a spectrophotometer to measure the absorbance of the sample solution A at 580 nm, substitute it into the standard working curve A, and calculate the content of free aldehyde groups.

[0038] (1.4) Detection limit

[0039] The detection limit was calculated as 3.3σ / S, where σ is the standard deviation and S is the slope of the standard curve. The calculated result was 0.065μg / g.

[0040] (1.5) Accuracy and precision

[0041] The accuracy and precision of the recovery rate and precision of the detection method for free aldehyde content were investigated, requiring the average recovery rate to be 80%-120% and RSD (n=9) ≤ 50%.

[0042] Low concentration accuracy test solution: Accurately measure a medical device product (0.5 g) containing 0.65 μg of free aldehyde group, place it in a 50 ml volumetric flask, add 1 ml of 25 μg / mL aldehyde group standard working solution, and shake well. Prepare 3 copies in parallel.

[0043] Medium concentration accuracy test solution: Accurately measure a medical device product (0.5 g) containing 0.65 μg of free aldehyde group, place it in a 50 ml volumetric flask, add 1 ml of 50 μg / mL aldehyde group standard working solution, and shake well. Prepare 3 copies in parallel.

[0044] High concentration accuracy test solution: Accurately measure a medical device product (0.5 g) containing 0.65 μg of free aldehyde group, place it in a 50 ml volumetric flask, add 1 ml of 75 μg / mL aldehyde group standard working solution, and shake well. Prepare 3 copies in parallel.

[0045] The recovery and precision of the detection method for free aldehyde content in Example 1 are shown in Table 2.

[0046] Table 1 Recovery and precision of the detection method for free aldehyde content in Example 1

[0047]

[0048]

[0049] (2) The specific steps of the method for detecting the total aldehyde content are:

[0050] (2.1) Preparation of Blank Working Solution B (Extracting Solution B) Using deionized water as solvent, an aqueous solution containing 0.5 mol / L phosphoric acid and 0.2 mol / L methanol was prepared as extracting solution B, ie, blank working solution B.

[0051] (2.2) Preparation of standard working solution B and drawing of standard working curve B

[0052] Using extract B as solvent, prepare a series of aldehyde-extract B solutions with concentrations of 10 μg / mL, 5 μg / mL, 2 μg / mL, 1 μg / mL, and 0.5 μg / mL as standard working solution B, and use extract B as blank working solution. Take 1.0 mL of standard working solution and 1.0 mL of blank working solution in test tubes, add 0.30 mL of alkaline red hydrochloride solution and shake and mix, add 0.50 mL of sodium sulfite and shake and mix, let stand for 50 minutes, and then use a spectrophotometer to measure the absorbance of standard working solution B and blank working solution B at 580 nm, and use aldehyde concentration as the horizontal axis and absorbance value as the vertical axis to draw the standard working curve B of total aldehyde content.

[0053] (2.3) Preparation of sample solution B and detection of total aldehyde content

[0054] In triplicate, accurately weigh approximately 50 mg of collagen sponge (approximately 15 mm x 15 mm product), record the exact weight, and transfer it to a polypropylene screw-top glass bottle.

[0055] Add 5 mL of extract B to the collagen sponge bottle, cover tightly, and place on an orbital shaker. Place the vial on one side of the orbital shaker, adjust the orbital shaker speed to 100 rpm, and stir and extract at 90°C for 60 minutes. Then transfer the solution from the sponge vial to a new label bottle, and add 5 mL of extract B to the sponge vial. Repeat the extraction 4 times in total, and combine the extracts as the sample solution B to be tested. Take 1.0 mL of the sample solution B to be tested in a test tube, add 0.30 mL of alkaline red hydrochloride solution and shake to mix, add 0.50 mL of sodium sulfite and shake to mix, let stand for 50 minutes, and then use a spectrophotometer to measure the absorbance of the sample solution B at 580 nm, substitute it into the standard working curve B, and calculate the total aldehyde content.

[0056] (2.4) Detection limit

[0057] The detection limit was calculated as 3.3σ / S, where σ is the standard deviation and S is the slope of the standard curve. The calculated result was 0.082μg / g.

[0058] (2.5) Accuracy and precision

[0059] The accuracy and precision of the recovery rate and precision of the detection method for free aldehyde content were investigated, requiring the average recovery rate to be 80%-120% and RSD (n=9) ≤ 50%.

[0060] Low concentration accuracy test solution: Accurately measure a medical device product (0.5 g) containing 0.82 μg of free aldehyde groups, place it in a 50 ml volumetric flask, add 1 ml of 25 μg / mL aldehyde standard working solution, and shake well. Prepare 3 copies in parallel.

[0061] Medium concentration accuracy test solution: Accurately measure a medical device product (0.5 g) containing 0.82 μg of free aldehyde group, place it in a 50 ml volumetric flask, add 1 ml of 50 μg / mL aldehyde group standard working solution, and shake well. Prepare 3 copies in parallel.

[0062] High concentration accuracy test solution: Accurately measure a medical device product (0.5 g) containing 0.82 μg of free aldehyde groups, place it in a 50 ml volumetric flask, add 1 ml of 75 μg / mL aldehyde standard working solution, and shake well. Prepare 3 copies in parallel.

[0063] The recovery and precision of the detection method for total aldehyde content in Example 1 are shown in Table 2.

[0064] Table 2 Recovery and precision of the detection method for total aldehyde content in Example 1

[0065]

[0066] Embodiment 2-6

[0067] Examples 2-6 respectively provide a method for detecting the aldehyde content in a medical device product.

[0068] The difference between the above embodiment and embodiment 1 is that the type of extract A is different, as shown below.

[0069] In Example 2, deionized water was used as solvent to prepare an aqueous solution containing 0.9 wt % sodium chloride, 0.5 t % saturated alkane n-heptane, and 2 wt % dimethyl sulfoxide as extracting solution A, ie, blank working solution A.

[0070] In Example 3: deionized water was used as solvent to prepare an aqueous solution containing 0.7 wt % sodium chloride, 0.8 wt % saturated alkane n-hexane, and 3 wt % dimethyl sulfoxide as extracting solution A.

[0071] In Example 4, deionized water was used as solvent to prepare an aqueous solution containing 1.1 wt % sodium chloride, 0.2 wt % saturated alkane n-hexane, and 1 wt % dimethyl sulfoxide as extract A.

[0072] In Example 5, deionized water was used as solvent to prepare an aqueous solution containing 0.8 wt % sodium chloride, 0.6 wt % saturated alkane n-hexane, and 2.5 wt % dimethyl sulfoxide as extract A.

[0073] In Example 6: deionized water was used as solvent to prepare an aqueous solution containing 1.2 wt % sodium chloride, 0.4 wt % saturated alkane n-hexane, and 1.5 wt % dimethyl sulfoxide as extract A.

[0074] The other process parameters in the above embodiment are the same as those in embodiment 1.

[0075] Examples 7-10

[0076] Examples 7-10 respectively provide a method for detecting the aldehyde content in a medical device product.

[0077] The difference between the above embodiment and embodiment 1 is that the stirring extraction temperature in the preparation method of the sample liquid A to be tested is different, as shown below.

[0078] In Example 7: In the method for preparing the test sample solution A, the stirring extraction temperature is 30°C.

[0079] In Example 8: In the method for preparing the test sample solution A, the stirring extraction temperature is 40°C.

[0080] In Example 9: In the method for preparing the test sample solution A, the stirring extraction temperature is 33°C.

[0081] In Example 10: In the method for preparing the test sample solution A, the stirring extraction temperature is 38°C.

[0082] The other process parameters in the above embodiment are the same as those in embodiment 1.

[0083] Examples 11-14

[0084] Examples 11-14 respectively provide a method for detecting the aldehyde content in a medical device product.

[0085] The difference between the above embodiment and embodiment 1 is that the type of extract B is different, as shown below.

[0086] In Example 11: deionized water was used as solvent to prepare an aqueous solution containing 0.4 mol / L phosphoric acid and 0.3 mol / L methanol as extract B.

[0087] In Example 12: deionized water was used as solvent to prepare an aqueous solution containing 0.6 mol / L phosphoric acid and 0.1 mol / L methanol as extract B.

[0088] In Example 13: deionized water was used as solvent to prepare an aqueous solution containing 0.45 mol / L phosphoric acid and 0.25 mol / L methanol as extract B.

[0089] In Example 14: deionized water was used as solvent to prepare an aqueous solution containing 0.55 mol / L phosphoric acid and 0.15 mol / L methanol as extract B.

[0090] The other process parameters in the above embodiment are the same as those in embodiment 1.

[0091] Examples 15-18

[0092] Examples 15-18 respectively provide a method for detecting the aldehyde content in a medical device product.

[0093] The difference between the above embodiment and embodiment 1 is that the stirring extraction temperature in the preparation method of the sample liquid B to be tested is different, as shown below.

[0094] In Example 15: In the method for preparing the test sample solution B, the stirring extraction temperature is 85°C.

[0095] In Example 16: In the method for preparing the test sample solution B, the stirring extraction temperature is 95°C.

[0096] In Example 17: In the method for preparing the test sample solution B, the stirring extraction temperature is 88°C.

[0097] In Example 18: In the method for preparing the test sample solution B, the stirring extraction temperature is 93°C.

[0098] The other process parameters in the above embodiment are the same as those in embodiment 1.

[0099] Comparative Example

[0100] Comparative Examples 1-4

[0101] Comparative Examples 1-4 respectively provide a method for detecting the aldehyde content in a medical device product.

[0102] The difference between the comparative example and Example 1 is that the type of the extracting solution A or the stirring extraction temperature in the preparation method of the sample solution A is different, as shown below.

[0103] In Comparative Example 1: deionized water was used as solvent to prepare an aqueous solution containing 0.9 wt % of sodium chloride as extract A.

[0104] In Comparative Example 2: deionized water was used as solvent to prepare an aqueous solution containing 0.6 wt % sodium chloride, 1.5 wt % saturated alkane n-hexane, and 0.5 wt % dimethyl sulfoxide as extract A.

[0105] In Comparative Example 3: In the preparation method of the test sample solution A, the stirring extraction temperature is 25°C.

[0106] In Comparative Example 4: In the preparation method of the test sample solution A, the stirring extraction temperature is 45°C.

[0107] The other process parameters in the above comparative example are the same as those in Example 1.

[0108] Comparative Examples 5-8

[0109] Comparative Examples 5-8 respectively provide a method for detecting the aldehyde content in a medical device product.

[0110] The difference between the comparative example and Example 1 is that the type of the extracting solution B or the stirring extraction temperature in the preparation method of the sample solution B is different, as shown below.

[0111] In Comparative Example 5: deionized water was used as solvent to prepare an aqueous solution containing 0.5 mol / L phosphoric acid as extract B.

[0112] In Comparative Example 6: deionized water was used as solvent to prepare an aqueous solution containing 0.8 mol / L phosphoric acid and 0.05 mol / L methanol as extract B.

[0113] In Comparative Example 7: In the preparation method of the test sample solution B, the stirring extraction temperature is 80°C.

[0114] In Comparative Example 8: In the preparation method of the test sample solution B, the stirring extraction temperature is 99°C.

[0115] The other process parameters in the above comparative example are the same as those in Example 1.

[0116] Performance testing

[0117] According to the detection method in Example 1, the detection limits, average values ​​of the accuracy and the precision of the detection methods in Examples 1-18 and Comparative Examples 1-8 were determined.

[0118] Test results: as shown in Table 3.

[0119] Table 3 Performance test results of the detection methods in Examples 1-18 and Comparative Examples 1-8

[0120]

[0121]

[0122] Combined with Table 3, by comparing the detection limits and accuracy averages and precision test results of the detection methods in Examples 1-18 and Comparative Examples 1-8, it can be seen that the detection method of the present application is used to detect the free aldehyde content and the total aldehyde content in medical device products, which has the advantages of low detection limit, high accuracy and precision.

[0123] Although the present invention has been described in detail above with general descriptions and specific embodiments, it is obvious to those skilled in the art that some modifications or improvements may be made thereto based on the present invention. Therefore, these modifications or improvements made without departing from the spirit of the present invention all fall within the scope of protection claimed by the present invention.

Claims

1. A method for detecting the aldehyde content in a collagen sponge, characterized in that: The specific steps include: Place the collagen sponge sample in extracting solution A, place it in an orbital shaker at a speed of 100 rpm, stir and extract for 50-80 minutes at 30-40°C, repeat the extraction 3-5 times, combine the extracts as the sample solution A to be tested, add alkaline red hydrochloride solution and sodium sulfite solution, shake and react at room temperature, let it stand for 45-55 minutes, and then use spectrophotometry and standard working curve to determine the free aldehyde content in the collagen sponge; The extract A is composed of the following components: 0.7-1.1wt% sodium chloride, 0.2-0.8wt% saturated alkane, 1-3wt% dimethyl sulfoxide, and the solvent is water; the saturated alkane is selected from any one of n-heptane and n-hexane; the solid-liquid ratio of the collagen sponge sample to the extract A is 45-55mg:4.5-5.5mL; Place the collagen sponge sample in the extracting solution B, place it in an orbital shaker at a speed of 100 rpm, stir and extract for 50-80 minutes at 85-95°C, add alkaline red hydrochloride solution and sodium sulfite solution as the sample solution B to be tested, shake and react at room temperature, let it stand for 45-55 minutes, and then use spectrophotometry and standard working curve to determine the total aldehyde content in the collagen sponge; The extract B is composed of the following components: 0.4-0.6 mol / L phosphoric acid, 0.1-0.3 mol / L methanol, and the solvent is water; the solid-liquid ratio of the collagen sponge sample to the extract B is 45-55 mg: 4.5-5.5 mL; The measuring point of the spectrophotometry is 580 nm; The alkaline red hydrochloride solution is an alkaline red hydrochloride aqueous solution containing 5.0-5.4 mmol / L alkaline red and 2.2-2.6 mol / L hydrochloric acid; the volume ratio of the alkaline red hydrochloride solution to the sample solution A to be tested is 0.2-0.4:1; the volume ratio of the alkaline red hydrochloride solution to the sample solution B to be tested is 0.2-0.4:1; The sodium sulfite solution is a sodium sulfite aqueous solution with a concentration of 7.5-8.5 mmol / L; the volume ratio of the sodium sulfite aqueous solution to the sample solution A to be tested is 0.4-0.6:1; the volume ratio of the sodium sulfite aqueous solution to the sample solution B to be tested is 0.4-0.6:

1.

2. The method for detecting the aldehyde content in the collagen sponge according to claim 1, characterized in that: The extract A is composed of the following components in concentrations: 0.8-1.0 wt % sodium chloride, 0.4-0.6 wt % saturated alkane, 1.5-2.5 wt % dimethyl sulfoxide, and the solvent is water.

3. The method for detecting the aldehyde content in the collagen sponge according to claim 1, characterized in that: The extract B is composed of components with the following concentrations: 0.45-0.55 mol / L phosphoric acid, 0.15-0.25 mol / L methanol, and the solvent is water.

4. The method for detecting the aldehyde content in the collagen sponge according to claim 1, characterized in that: The method for drawing the standard working curve of the free aldehyde content is as follows: using extract A as a solvent, preparing a series of aldehyde-extract A solutions with concentrations of 10 μg / mL, 5 μg / mL, 2 μg / mL, 1 μg / mL, and 0.5 μg / mL as standard working solution A, using extract A as a blank working solution, adding alkaline red hydrochloride solution and sodium sulfite solution, shaking and reacting at room temperature, standing for 45-55 minutes, and then using a spectrophotometer to measure the absorbance of the standard working solution A and the blank working solution A at 580 nm to draw the standard working curve of the free aldehyde content.

5. The method for detecting the aldehyde content in the collagen sponge according to claim 1, characterized in that: The method for drawing the standard working curve of the total aldehyde content is as follows: using the extract B as a solvent, preparing a series of aldehyde-extract B solutions with concentrations of 10 μg / mL, 5 μg / mL, 2 μg / mL, 1 μg / mL, and 0.5 μg / mL as the standard working solution B, using the extract B as the blank working solution B, adding alkaline red hydrochloride solution and sodium sulfite solution, shaking and reacting at room temperature, standing for 45-55 minutes, and then using a spectrophotometer to measure the absorbance of the standard working solution and the blank working solution B at 580 nm to draw the standard working curve of the total aldehyde content.

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