Use of acrylic acid in the preparation of in vitro tissue localization and / or marking stains and stains

Abstract

The application provides application of acrylic acid in preparation of an in-vitro tissue positioning and / or marking dye. The application is the first to find that acrylic acid is applied in the form of an acrylic acid emulsion in preparation of an in-vitro tissue positioning dye, and that the water in the acrylic acid emulsion evaporates quickly to form a film, loses solubility due to rapid drying, and part of the polymer and color form a tough and elastic film on the surface, thereby realizing rapid positioning and dyeing of in-vitro tissue, especially rapid dyeing of in-vitro tissue margins.

Description

Technical Field

[0001] This invention belongs to the field of staining technology, specifically relating to the application of acrylic acid in the preparation of in vitro tissue localization and / or labeling stains and the stains themselves. Background Technology

[0002] With the development of medicine, precision medicine has gradually become the direction of modern medical development. In order to provide patients with more effective and targeted individualized treatment plans, clinicians have placed higher demands on the accuracy of pathological diagnosis. Determining the condition of the resected specimen margins under a microscope is one of the important tasks of pathological examination, which directly affects the patient's postoperative treatment and prognosis.

[0003] For example, a positive margin in any part of the surgical margin (which needs to be distinguished by different colors) of a breast-conserving surgery specimen indicates residual cancer within the preserved breast, directly leading to recurrence of cancer in the preserved breast after surgery. Therefore, multiple negative margins are crucial for the success of breast-conserving surgery, and the effective methods used to differentiate margins and perform accurate pathological diagnosis directly affect the determination of margins. The American Society of Surgical Oncology (SSO) and the American Society of Radiation Oncology (ASTRO) have jointly developed new guidelines for surgical margins in breast cancer surgery, which include: 1. Positive margin: Invasive carcinoma or ductal carcinoma in situ in the stained area, which increases the risk of ipsilateral breast cancer recurrence by at least 2 times. This risk cannot be offset by enhanced radiotherapy, systemic therapy, or favorable biological characteristics. 2. Negative margin: No tumor in the stained area, which reduces the recurrence rate of ipsilateral breast cancer.

[0004] In my country, gastrointestinal tumors account for more than half of all adult cancers. The five-year survival rate for early-stage gastrointestinal tumors after standardized treatment is over 90%, significantly higher than that for late-stage gastrointestinal tumors. The success of endoscopic mucosal resection and endoscopic mucosal dissection, crucial methods for early treatment, hinges on the presence of residual tumor at multiple surgical margins (distinguished by different colors). This is also a primary assessment criterion for determining whether further treatment is necessary. Furthermore, multiple studies on laryngeal cancer have shown that rapid frozen section pathological examination of intraoperative surgical margins (multiple margins, distinguished by different colors) to guide partial laryngectomy can maximize the preservation and reconstruction of laryngeal function while removing the tumor, thus improving the patient's quality of life. In addition, the determination of surgical margins is essential for radical resection of tumors in multiple systems, including the gastrointestinal tract, skin, soft tissue, respiratory, urinary, and reproductive systems. Therefore, achieving accurate pathological diagnosis of surgical margins using effective methods is of paramount importance.

[0005] Existing cutting edge staining techniques fall into two categories: 1. Traditional ink staining: This method involves carbon adsorbing onto the tissue surface, staining the cutting edge, which is then interpreted under a microscope. However, traditional ink staining is prone to smudging onto normal tissue, causing confusion between the cutting edge and normal tissue, resulting in inaccurate interpretation; 2. Imported multicolor cutting edge staining agents. These staining agents are either directly imported or repackaged domestically, but they are expensive and cannot be widely used, affecting the accuracy of patient reports and subsequent treatment. Summary of the Invention

[0006] To address, or at least partially address, the above-mentioned deficiencies, the present invention provides the use of acrylic acid in the preparation of in vitro tissue localization and / or labeling staining agents.

[0007] The first aspect of this invention provides the use of acrylic acid in the preparation of in vitro tissue localization and / or labeling staining agents.

[0008] Furthermore, the acrylic acid exists in the form of an acrylic emulsion.

[0009] In one specific embodiment, the acrylic emulsion comprises the following components in parts by weight: 1000 parts water, 4-6 parts acrylic acid, 15-25 parts color paste or color powder, and 45-55 parts styrene-acrylic emulsion.

[0010] Preferably, the acrylic emulsion comprises the following components in parts by weight: 1000 parts water, 5 parts acrylic acid, 20 parts color paste or color powder, and 50 parts styrene-acrylic emulsion.

[0011] As another specific embodiment, the acrylic emulsion comprises the following components in parts by weight: 1000 parts water, 4-6 parts acrylic acid, 15-25 parts color paste or color powder, and 18-22 parts adhesive powder.

[0012] Preferably, the acrylic emulsion comprises the following components in parts by weight: 1000 parts water, 5 parts acrylic acid, 20 parts color paste or color powder, and 20 parts adhesive powder.

[0013] Furthermore, the in vitro tissue localization staining agent includes at least one of in vitro tissue cutting edge staining agent and pathological tissue staining agent.

[0014] Furthermore, the in vitro tissue localization and / or labeling staining agent is used for fresh ex vivo tissue or fixed tissue specimens; or, The in vitro tissue localization and / or labeling staining agent is used for in vitro untreated adipose tissue; or, The in vitro tissue localization and / or labeling staining agents are used for human in vitro tissues.

[0015] A second aspect of the present invention provides an in vitro tissue localization and / or labeling staining agent comprising acrylic acid.

[0016] Furthermore, the acrylic acid exists in the form of an acrylic emulsion, which comprises the following components in parts by weight: 1000 parts water, 4-6 parts acrylic acid, 15-25 parts color paste or color powder, 45-55 parts styrene-acrylic emulsion or 18-22 parts adhesive powder.

[0017] Compared with the prior art, the present invention has the following beneficial effects: This invention provides the application of acrylic acid in the preparation of in vitro tissue localization and / or labeling stains. This invention is the first to discover that by applying acrylic acid in the preparation of in vitro tissue localization stains, the acrylic acid is used in the form of an acrylic emulsion. The acrylic emulsion rapidly forms a film through water evaporation, quickly dries to lose its solubility, and partially polymerizes and pigments to form a tough and elastic film on the surface, thereby achieving rapid localization staining of in vitro tissues, especially rapid staining of in vitro tissue cutting edges. Furthermore, the application of acrylic acid in the preparation of in vitro tissue localization stains in this invention results in stains that are inexpensive, offer rich colors, are non-toxic and environmentally friendly, have fast staining speeds, require small dosages, and produce good results. No special treatment is needed for any tissue, thus overcoming the shortcomings of existing technologies. Attached Figure Description

[0018] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0019] Figure 1 These are comparative images of the in vitro tissue (intestine) localization staining results of acrylic emulsion and existing ink in Example 1 of this invention; Figure 2 These are comparative images of the in vitro tissue (intestine) localization staining results of six different colored acrylic emulsions and different colored dyes from abroad, as described in Example 2 of this invention. Figure 3 These are color rendering images of the acrylic emulsion in various cutting edge structures (paraffinic structures) in Example 3 of the present invention; Figure 4 This is a staining effect diagram of acrylic emulsion in rapid pathology (fresh laryngeal mucosa tissue) in Example 4 of the present invention; Figure 5 This is a colorimetric effect diagram of the propylene emulsion in a gastric mucosal ablation specimen in Example 5 of the present invention; Figure 6This is a coloring effect image of propylene emulsion in a routine breast section in Example 6 of the present invention; Figure 7 This is a physical diagram of the blue acrylic emulsion preparation in Example 3 of the present invention; Figure 8 This is a photograph of the stained in vitro tissue in Example 2 of the present invention; Figure 9 These are comparative images showing the results of in vitro tissue (intestine) localization staining with six different colored acrylic emulsions in Example 2 of this invention and six different colored staining agents in Comparative Example 1. Detailed Implementation

[0020] The following embodiments are provided to better understand the present invention and are not limited to the preferred embodiments described. They do not constitute a limitation on the content and scope of protection of the present invention. Any product that is the same as or similar to the present invention, derived by any person under the guidance of the present invention or by combining the features of the present invention with other prior art, falls within the protection scope of the present invention.

[0021] With the development of medicine, precision medicine has gradually become the direction of modern medical development. In order to provide patients with more effective and targeted individualized treatment plans, clinicians have put forward higher requirements for the accuracy of pathological diagnosis. Determining the condition of multiple surgical margins under a microscope is one of the important tasks of pathological examination, directly related to the patient's postoperative treatment and prognosis. While traditional ink staining technology is inexpensive, its staining time is long. Too short a time results in poor staining effect and difficulty in interpreting the surgical margins under a microscope; too long a time is unsuitable for rapid pathological tissue examination during surgery, and it is prone to smudging, causing the margins to be confused with normal tissue, resulting in inaccurate interpretation. Furthermore, it cannot meet the requirement of differentiating staining multiple sites and multiple margins. Some foreign multicolor margin staining agents have requirements for the tissue type of the margin sample. For adipose tissue, special treatment is required. For example, lipomas and gastrointestinal margins often contain adipose tissue, which can affect their interpretation. In addition, the process is complicated, staining is often poor, and the price is high, making it difficult to popularize and implement, thus affecting the accuracy of patient reports and further impacting patient prognosis and treatment.

[0022] Therefore, this invention provides an application of acrylic acid in the preparation of in vitro tissue localization and / or labeling staining agents. Although there are many types of dyes, very few meet the requirements for in vitro staining. They must meet the following requirements: 1. Insoluble in many solvents such as water, formaldehyde, alcohol, and xylene; heat-resistant and low-temperature resistant; and with good stability. After specimen localization and staining, several processes are required, including fixation, dehydration, and embedding, followed by paraffin embedding at 60 degrees Celsius and freezing at -20 degrees Celsius. High stability of the staining agent is required; it must not bleed and must provide a clear contrast with the tissue. 2. Precise localization and rapid staining. Especially in rapid intraoperative pathological examinations, the diagnosis of a specimen needs to be completed within 30 minutes of receipt. Therefore, the staining agent must form a film quickly and not easily bleed to other locations to avoid delaying or misleading diagnostic conclusions and affecting patient safety. 3. Stainable for a wide variety of tissues and organs. The human body has many types of organs with different tissue compositions, requiring products that can stain a wide range of tissues and organs. To solve these problems, after extensive experimental research, the inventors surprisingly and pioneeredly discovered that by applying acrylic acid in the preparation of in vitro tissue localization and / or labeling staining agents, acrylic acid is used in the form of an acrylic emulsion. It was found that when the acrylic emulsion is applied to in vitro tissue localization and / or labeling staining, the water evaporates rapidly to form a film, dries quickly and loses its solubility, and some polymers and pigments form a tough and elastic film on the surface, thereby achieving rapid localization staining of in vitro tissues, especially rapid staining of in vitro tissue cutting edges.

[0023] This invention applies acrylic acid to the preparation of in vitro tissue localization and / or labeling staining agents, providing rich colors to differentiate staining of multiple sites and multiple cutting edges. It offers short staining time and strong coverage. The semi-solid state prevents smudging, provides excellent staining results, and is waterproof. Compared to the high price of imported products, this invention is cost-effective, allowing it to overcome the limitations of foreign technology and be widely applied domestically, thus comprehensively improving the level of precision medicine.

[0024] Meanwhile, in practical applications, it helps maintain proper tissue orientation for surgical specimens; identifies multiple processed tissues within the same tissue cassette; and serves as a staining agent for pathological tissues, allowing for observation of the distance between the tumor and the surgical margin or the depth of invasion through staining.

[0025] In one specific embodiment, the acrylic emulsion comprises the following components by weight: 1000 parts water, 4-6 parts acrylic acid, 15-25 parts color paste or color powder, and 45-55 parts styrene-acrylic emulsion. For example, 4, 5, or 6 parts acrylic acid; 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 parts color paste or color powder; and 45, 48, 49, 50, 51, 52, 53, 54, or 55 parts styrene-acrylic emulsion. To match the localization and / or labeling staining of in vitro tissues, the inventors optimized the formulation types and ratios to achieve rapid staining speed. The stained tissue can be permanently stained after air drying at room temperature for 1 minute, resulting in excellent staining effects.

[0026] Preferably, the acrylic emulsion comprises the following components in parts by weight: 1000 parts water, 5 parts acrylic acid, 20 parts color paste or color powder, and 50 parts styrene-acrylic emulsion.

[0027] In another specific embodiment, the acrylic emulsion comprises the following components in parts by weight: 1000 parts water, 4-6 parts acrylic acid, 15-25 parts pigment paste or powder, and 18-22 parts adhesive powder. For example, 4, 5, or 6 parts acrylic acid; 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 parts pigment paste or powder; and 18, 19, 20, 21, or 22 parts adhesive powder. To match the localization and / or labeling staining of in vitro tissues, the inventors optimized the formulation types and ratios to achieve rapid staining speed. The stained tissue can be permanently stained after air drying at room temperature for 1 minute, resulting in excellent staining effects.

[0028] Preferably, the acrylic emulsion comprises the following components in parts by weight: 1000 parts water, 5 parts acrylic acid, 20 parts color paste or color powder, and 20 parts adhesive powder.

[0029] In practical applications, you can mix 1000 grams of water, 20 grams of color paste or color powder, 50 grams of styrene-acrylic emulsion or 20 grams of adhesive powder, and add 5 grams of acrylic acid during the mixing process.

[0030] Furthermore, the in vitro tissue localization staining agent includes at least one of in vitro tissue cutting edge staining agent and pathological tissue staining agent.

[0031] Furthermore, the in vitro tissue localization and / or labeling staining agent is used for fresh ex vivo tissue or fixed tissue specimens; or, The in vitro tissue localization and / or labeling staining agent is used for in vitro untreated adipose tissue; or, The in vitro tissue localization and / or labeling staining agents are used for human in vitro tissues.

[0032] In addition, the present invention provides an in vitro tissue localization and / or labeling staining agent, comprising acrylic acid.

[0033] Furthermore, the acrylic acid exists in the form of an acrylic emulsion, which comprises the following components in parts by weight: 1000 parts water, 4-6 parts acrylic acid, 15-25 parts color paste or color powder, 45-55 parts styrene-acrylic emulsion or 18-22 parts adhesive powder.

[0034] The specific staining methods used in the following in vitro tissue localization staining experiments are as follows: (1) The staining agent can be used immediately; do not dilute it before use. (2) Wipe the liquid off the surface of the tissue to be stained (fresh tissue or tissue fixed with formalin). This is suitable for tissues rich in fat. No special treatment is required for tissues rich in fat (such as mammary glands). (3) Squeeze out an appropriate amount of staining agent and apply it evenly to the specific tissue area that needs to be located; (4) After staining, the tissue is allowed to air dry at room temperature for 1-2 minutes, and the dye will then permanently adhere to the surface of the specimen; (5) Close the bottle cap and you can continue with the subsequent processing procedures for the tissue specimen. Please try to avoid direct contact with the stained area during subsequent operations.

[0035] During the staining process, please note the following: 1. This product is not suitable for staining living tissues; 2. After use, please tighten the cap promptly to prevent the stain from drying and hardening. If stain residue at the bottle opening hardens and causes blockage, you can wipe it with a damp cotton swab to moisten the opening; 3. If the stain accidentally gets into your eyes, rinse immediately with plenty of water and seek medical attention promptly.

[0036] The acrylic emulsion provided in this invention is used for the direct marking and localization of fresh or fixed tissue specimens. The staining agent is non-toxic and environmentally friendly, with fast staining speed, small dosage, and good results, achieving permanent staining of tissues. No special treatment is required for the tissue, and it shows excellent staining effects, especially for untreated adipose tissue. Multiple colors can be used in combination to meet the needs of tissue specimen orientation. The staining agent is used for marking and staining localization of tissue edges. It is applicable to both fresh tissues and formalin-fixed tissue specimens, but not for staining living tissues. The acrylic in vitro tissue localization staining agent should be stored in a sealed container at room temperature, protected from light and direct sunlight. Do not refrigerate or freeze. Tighten the cap immediately after each use and use as soon as possible after opening. The in vitro tissue localization staining agent is used for marking and localization of fresh and fixed tissue specimens. The staining agent is non-toxic and environmentally friendly, with excellent staining effects. It stains quickly; the stained tissue can be permanently stained after air drying at room temperature for 1 minute. The dosage is small; each bottle can meet the needs of approximately 4000 cm² of tissue. 2 Staining is approximately equivalent to staining a standard surgical edge 1000 times; it can achieve permanent staining of tissues. Multiple colors can be used in different combinations to meet the needs of tissue specimen orientation. A rich color palette is available; initially, four colors with good microscopic contrast are selected, and new colors can be added later as needed.

[0037] The detailed implementation methods are as follows: Example 1

[0038] This embodiment provides an application of acrylic emulsion in the preparation of in vitro tissue localization and / or labeling staining agents. First, the surface liquid of the in vitro tissue (intestine) to be stained is wiped dry; then, an appropriate amount of acrylic emulsion from this embodiment is evenly applied to the specific tissue area to be localized; finally, the stained tissue is allowed to air dry at room temperature for 1 minute, and the dye will permanently adhere to the specimen surface; wherein, in this embodiment, the acrylic emulsion formulation includes 1000g of water, 5g of acrylic acid, 20g of black pigment, and 50g of styrene-acrylic emulsion; As a control, in vitro tissues were stained using conventional ink in the same manner as in this embodiment.

[0039] The corresponding staining effect, such as Figure 1 As shown: Figure 1 A shows the color development effect of acrylic emulsion staining in this embodiment after 1 minute. A clear black band can be seen forming on the tissue surface. Figure 1 B shows the color development after 1 minute of ink staining, with virtually no obvious linear banding; only scattered black particles are visible around the edges. In comparison, this technique is easier to apply and produces excellent results. Compared to the limited color range of ink staining, the acrylic emulsion in this embodiment offers a richer color palette, better meeting diagnostic and therapeutic needs. Example 2

[0040] This embodiment provides an application of acrylic emulsion in the preparation of in vitro tissue localization and / or labeling staining agents. First, the surface liquid of the in vitro tissue (intestine) to be stained is wiped dry; then, an appropriate amount of acrylic emulsion from this embodiment is evenly applied to the specific tissue area to be localized; finally, the stained tissue is allowed to air dry at room temperature for 1 minute, and the dye is permanently attached to the specimen surface. In this embodiment, the acrylic emulsion formula includes 1000g of water, 5g of acrylic acid, 20g of pigment, and 50g of styrene-acrylic emulsion. The pigment includes green, blue, black, yellow, purple, and orange pigments, forming six different colored acrylic emulsions, which are then used for staining. As a control, in vitro tissues were stained using a foreign staining agent in the same manner as in this embodiment. The foreign staining agent was BIOGNOST, Switzerland, 3408-SET-7.

[0041] The corresponding staining effect, such as Figure 2 The image shows a comparison of the color development of six colors in the acrylic emulsion of this embodiment with that of foreign staining agents after one minute. The left side represents the embodiment of this invention, and the right side represents the foreign staining agents. The comparison shows that the embodiment of this invention can rapidly and linearly stain stably in any tissue (including untreated adipose tissue) within a short time, producing vibrant colors with clear contrast, making it easy to identify under a microscope. While foreign staining agents can also stain in a short time, their staining is dispersed, forming floating particles or clumps, and the staining is discontinuous in some areas. Whether these areas can be identified as cutting edges under a microscope is debatable, affecting the accuracy of the results.

[0042] The corresponding stained in vitro tissue images are as follows: Figure 8 As shown. Example 3

[0043] This embodiment provides an application of acrylic emulsion in the preparation of in vitro tissue localization and / or labeling staining agents. First, the surface liquid of the in vitro tissue (intestine, larynx) to be stained is wiped dry; then, an appropriate amount of acrylic emulsion of this embodiment is evenly applied to the specific tissue area to be localized; finally, the stained tissue is allowed to air dry at room temperature for 2 minutes, and the dye can be permanently attached to the specimen surface. The corresponding staining effect, such as Figure 3 As shown, Figure 3 This is a diagram illustrating the colorimetric effect of acrylic emulsion in various cut tissues (paraffin tissue) according to an embodiment of the present invention. In this embodiment, the acrylic emulsion formulation includes 1000g water, 5g acrylic acid, 20g colorant, and 20g adhesive powder. The colorant includes black, purple, green, and blue colorants, forming four different colored acrylic emulsions, which are then used for staining. Black and purple are for the intestines, while green and blue are for the larynx. Figure 3It can be seen that the coloring effect shows that the color can be stably and linearly colored on the tissue surface, without impurities or interference, and the color contrast is obvious under the microscope, with excellent effect; The corresponding blue acrylic emulsion formulation is shown in the image below. Figure 7 As shown. Example

[0044] This embodiment provides an application of acrylic emulsion in the preparation of in vitro tissue localization and / or labeling staining agents. First, the surface liquid of the in vitro tissue (laryngeal resection specimen) to be stained is wiped dry; then, an appropriate amount of the acrylic emulsion of this embodiment is evenly applied to the specific tissue area to be localized; finally, the stained tissue is allowed to air dry at room temperature for 1 minute, and the dye will permanently adhere to the specimen surface; wherein, in this embodiment, the acrylic emulsion formula includes 1000g of water, 5g of acrylic acid, 20g of pigment, and 50g of styrene-acrylic emulsion, and the pigment includes black pigment and green pigment, forming two different colored acrylic emulsions, which are then used for staining; The corresponding staining effect, such as Figure 4 As shown, Figure 4 This is a staining effect image of acrylic emulsion in rapid pathology (fresh laryngeal mucosa tissue) according to an embodiment of the present invention. From... Figure 4 As can be seen, in the submitted laryngectomy specimen, the vertical width is about 1 cm. By using the acrylic emulsion staining and labeling microscope in this embodiment of the invention, the condition of the resection margin at different positions can be quickly and accurately identified, and the overall tumor infiltration can be judged. This avoids the confusion of the upper and lower resection margins and the incomplete observation of the tumor as a whole. Example 4

[0045] This embodiment provides an application of acrylic emulsion in the preparation of in vitro tissue localization and / or labeling staining agents. First, the surface liquid of the in vitro tissue (gastric mucosal ablation specimen) to be stained is wiped dry; then, an appropriate amount of the acrylic emulsion of this embodiment is evenly applied to the specific tissue area to be localized; finally, the stained tissue is allowed to air dry at room temperature for 1 minute, and the dye will permanently adhere to the specimen surface; wherein, in this embodiment, the acrylic emulsion formula includes 1000g of water, 5g of acrylic acid, 20g of pigment, and 50g of styrene-acrylic emulsion, and the pigment includes black pigment and green pigment, forming two different colored acrylic emulsions, which are then used for staining; The corresponding staining effect, such as Figure 5 As shown, Figure 5 This is a colorimetric effect diagram of the propylene emulsion in a mucosal ablation specimen, as shown in an embodiment of the present invention. Figure 5 As can be seen, we applied staining in the rapidly developing mucosal ablation technology. The results show that by using different staining methods with acrylic emulsion in the embodiments of this invention to interpret the relationship between lesions and different cutting edges, the measurement of the distance between lesion depth and basal cutting edge is more accurate and precise. Example 5

[0046] This embodiment provides an application of acrylic emulsion in the preparation of in vitro tissue localization and / or labeling staining agents. First, the surface liquid of the in vitro tissue (routine breast section) to be stained is wiped dry; then, an appropriate amount of acrylic emulsion from this embodiment is evenly applied to the specific tissue area to be localized; finally, the stained tissue is allowed to air dry at room temperature for 1 minute, and the dye will permanently adhere to the specimen surface; wherein, in this embodiment, the acrylic emulsion formulation includes 1000g of water, 5g of acrylic acid, 20g of black pigment, and 50g of styrene-acrylic emulsion; The corresponding staining effect, such as Figure 6 As shown, Figure 6 This is an image showing the staining effect of propylene emulsion in routine breast tissue sections according to an embodiment of the present invention. Figure 6 It can be seen that no special treatment is needed for staining of fatty tissue, and the image shows that the basal resection margin (black mark) is less than 1 mm away from the carcinoma in situ (the negative requirement is greater than 2 mm), indicating that the patient has a high risk of recurrence. Example 6

[0047] This embodiment provides an application of acrylic emulsion in the preparation of in vitro tissue localization and / or labeling staining agents, the same as in Embodiment 1, except that: in this embodiment, the acrylic emulsion formulation includes 1000g of water, 7g of acrylic acid, 20g of black pigment, and 50g of styrene-acrylic emulsion; in this embodiment, a black band is formed on the tissue surface, but the clarity is lower than that of the black band in Embodiment 1, but it is significantly better than the staining effect of the ink in Embodiment 1. Example 7

[0048] This embodiment provides an application of acrylic emulsion in the preparation of in vitro tissue localization and / or labeling staining agents, the only difference being that: in this embodiment, the acrylic emulsion formulation includes 1000g of water, 3g of acrylic acid, 20g of black pigment, and 50g of styrene-acrylic emulsion; in this embodiment, a black band is formed on the tissue surface, but the clarity is also lower than that of the black band in Example 1, but it is still significantly better than the staining effect of the ink in Example 1. Comparative Example 1

[0049] This comparative example provides an in vitro tissue localization and / or labeling staining agent, the same as in Example 2, except that: in this comparative example, the staining agent formulation includes 1000g of water, 20g of pigment, and 50g of styrene-acrylic emulsion; the pigment includes green pigment, blue pigment, black pigment, yellow pigment, purple pigment, and orange pigment, forming 6 different colored staining agents, which are then used for staining. pass Figure 9The staining results show that the staining agent without added acrylic acid cannot form a linear color band on the tissue. Instead, it diffuses in a granular manner, which easily contaminates the surrounding tissue and cannot achieve the effect of localization.

[0050] From the above embodiments and comparative experiments, it can be seen that the acrylic emulsion used in the embodiments of the present invention provides rich colors, can distinguish and stain multiple sites and multiple surgical edges, has a short staining time, strong coverage, accurate positioning, a semi-solid state, is not prone to smudging, dries quickly to form a film and is waterproof, has excellent staining effect under a microscope, and is non-toxic and environmentally friendly. It can also compensate for and replace traditional ink staining. Compared with the high price of imported products, the acrylic emulsion in the embodiments of the present invention is low in cost, can overcome the limitations of foreign technology, and can be widely used domestically, comprehensively improving the level of precision medicine. In addition, the acrylic emulsion in the embodiments of the present invention can stain well in various tissues (including adipose tissue) without special treatment, and has a short production cycle and low price. In contrast, foreign products are expensive, and some have requirements for tissue type. For adipose tissue, special treatment is required, the process is complicated, and the staining is poor. Furthermore, adipose tumors and gastrointestinal surgical edges often contain adipose tissue, which affects their interpretation. Compared with other technologies, the acrylic emulsion in the embodiments of the present invention is easier to popularize and implement, thereby improving the level of precision diagnosis and treatment for patients.

[0051] Obviously, the above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. The application of acrylic acid in the preparation of in vitro tissue localization and / or labeling staining agents, wherein, The acrylic acid exists in the form of an acrylic emulsion, which comprises the following components by weight: 1000 parts water, 4-6 parts acrylic acid, 15-25 parts color paste or color powder, 45-55 parts styrene-acrylic emulsion or 18-22 parts adhesive powder.

2. The application according to claim 1, characterized in that, The acrylic emulsion comprises the following components in parts by weight: 1000 parts water, 5 parts acrylic acid, 20 parts color paste or color powder, and 50 parts styrene-acrylic emulsion.

3. The application according to claim 1, characterized in that, The acrylic emulsion comprises the following components in parts by weight: 1000 parts water, 5 parts acrylic acid, 20 parts color paste or color powder, and 20 parts adhesive powder.

4. The application according to any one of claims 1-3, characterized in that, The in vitro tissue localization staining agent includes at least one of in vitro tissue cutting edge staining agent and pathological tissue staining agent.

5. The application according to any one of claims 1-3, characterized in that, The in vitro tissue localization and / or labeling staining agent is used for fresh ex vivo tissue or fixed tissue specimens; or, The in vitro tissue localization and / or labeling staining agent is used for in vitro untreated adipose tissue; or, The in vitro tissue localization and / or labeling staining agents are used for human in vitro tissues.

6. An in vitro tissue localization and / or labeling staining agent, characterized in that, Includes acrylic acid, wherein the acrylic acid exists in the form of an acrylic emulsion, the acrylic emulsion comprising the following components by weight: 1000 parts water, 4-6 parts acrylic acid, 15-25 parts color paste or color powder, 45-55 parts styrene-acrylic emulsion or 18-22 parts adhesive powder.

Images