Application of self-heating patch in male animal contraception

Abstract

The invention discloses application of a self-heating patch in male animal contraception. The self-heating patch is prepared from iron powder, activated carbon, kieselguhr, sodium chloride and water. According to the invention, the influence of the size of the iron powder and the proportioning ratio of the components on the heating temperature is explored, and the influence of different heating patches on spermatogenesis and fertility of male mice is explored respectively; the obtained results jointly show that the spontaneous heating patch disclosed by the invention has huge application potential in the aspect of male animal contraception (such as pet contraception).

Description

Technical Field

[0001] The invention belongs to the technical field of biomedicine, and in particular relates to the application of a self-heating patch in male animal contraception. Background Art

[0002] With the rapid development of modern society, male animal contraception is considered the most effective way to control the surge in the number of experimental animals and household pets. Current methods using surgical methods, chemical injections, and anti-fertility vaccines have addressed key aspects of male animal contraception and achieved remarkable results. Despite their usefulness, male animal contraceptive surgery, such as vasectomy, usually involves multiple steps and is directly dependent on the skill proficiency of the veterinarian. In addition, vasectomy has surgical risks, and reversal surgery is not easy to succeed (<50%). Other routes, such as chemical injections and anti-fertility vaccines can cause long-term adverse reactions and unnecessary immunosuppression, so that fertility during the chemical or immunization period may be restored, resulting in contraceptive failure. In this regard, a non-surgical but effective alternative male animal contraception method with negligible side effects is very much needed.

[0003] The spermatogenesis process of male animals depends on temperature changes. Slightly heating the testicles will temporarily inhibit spermatogenesis and lead to infertility. When the heat source is removed for a period of time, spermatogenesis and fertility can be restored. Initial studies have shown that thermal contraception is a safe and effective male contraceptive method. Hot water baths were the first method used to systematically study thermal contraception; however, its low heating efficiency and non-targeted nature hindered the widespread application of thermal contraception. With the rapid development of nanotechnology, the unique properties of various nanomedia have also been used in the study of male contraception. For example, the photothermal effect of gold nanorods and the magnetocaloric effect of magnetic iron oxide can be used for precise heating of the testicles to achieve male reversible contraception. However, the severe pain during the injection of gold nanorods, the damage of light to the skin, the chronic toxicity caused by non-degradability, and the inconvenience of intravenous injection for iron oxide administration have all limited its progressive clinical research. Therefore, the development of a safe, effective and convenient means of testicular heating is a key problem in achieving thermal contraception in male animals.

[0004] In recent years, self-heating patches have been used in a variety of scenarios due to their convenience, safety, effectiveness, and low price, such as anti-inflammatory and analgesic, blood circulation and blood stasis, and improvement of microcirculation function. Based on different application sites, different heating patches are popular on the market, such as uterine warming patches, foot heating patches, knee and waist heating patches, etc. Therefore, heating the testicles with a self-heating patch may be a convenient means of achieving male thermal contraception. However, the degree of inhibition of spermatogenesis and fertility in males depends on the degree and duration of testicular heating. Therefore, it is of practical significance to achieve reversible contraception in male animals by designing the heating temperature and heating time of the self-heating patch. Summary of the invention

[0005] In order to solve the technical problems existing in thermal contraception, the present invention develops a safe, effective and convenient testicular thermal therapy method.

[0006] The technical solution adopted by the present invention is as follows:

[0007] The invention discloses an application of a self-heating patch in male animal contraception. The self-heating patch is made of iron powder, water, activated carbon, sodium chloride and diatomaceous earth.

[0008] Furthermore, the raw material ratio of the self-heating patch is: 3.0-5.0 g of iron powder, 1.1-1.9 mL of water, 0.4-1.0 g of activated carbon, 0.3-0.8 g of sodium chloride, and 2.0-3.0 g of diatomaceous earth.

[0009] Furthermore, the raw material ratio of the self-heating patch is: 3.0g iron powder, 1.1mL water, 0.4g activated carbon, 0.3g sodium chloride, and 3.0g diatomaceous earth.

[0010] Furthermore, the raw material ratio of the self-heating patch is: 4.0g iron powder, 1.5mL water, 1.0g activated carbon, 0.8g sodium chloride, and 2.0g diatomaceous earth.

[0011] Furthermore, the raw material ratio of the self-heating patch is: 5.0g iron powder, 1.9mL water, 0.75g activated carbon, 0.5g sodium chloride, and 2.0g diatomaceous earth.

[0012] Furthermore, the particle size of the iron powder is 0.2-50 μm, preferably 10 μm.

[0013] Furthermore, the application is to place the self-heating patch on the testicles to achieve contraception in male animals.

[0014] The heating patch of the present invention comprises iron powder, activated carbon, diatomaceous earth, sodium chloride and water. Among them, iron powder is the main material of the heating patch. Iron powder undergoes an oxidation-reduction reaction with oxygen in the air. This process is an exothermic reaction, that is, heat energy is released; iron powders of different sizes have different surface areas, different areas in contact with oxygen, different reaction speeds, and different amounts of heat released. Water is an important catalyst for the heating of iron powder. Adding water will accelerate the reaction, making the reaction faster and more intense, so that the heating patch can quickly generate enough heat. Activated carbon and diatomaceous earth have the function of absorbing heat, which can stabilize the reaction of iron powder and water and avoid the rapid release of heat. Sodium chloride is mainly used to absorb trace moisture that penetrates into the heating patch to prevent the iron powder from gradually becoming ineffective. The heating patch produced is air-insulated packaging. Once the outer packaging is torn off, air will enter the bag, causing the iron powder to oxidize and generate heat. Placing it in the testicles can inhibit spermatogenesis to achieve the purpose of contraception.

[0015] The invention adjusts the heating temperature by changing the ratio of ingredients to make different heating patches, which are placed on the testicles to be heated to different degrees, thereby achieving reversible contraception. The self-heating patch of the invention has great application potential in male animal contraception (such as pet contraception).

[0016] Compared with the prior art, the present invention has the following beneficial effects:

[0017] (1) Easy to operate, non-traumatic, and can achieve reversible contraception: 45℃ heating patch can be used for male reversible contraception.

[0018] (2) Low cost and easy to make: All ingredients used in the heating patch are easily available and inexpensive, and the production process is simple. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 This is a trend chart of the impact of different ingredient ratios on the temperature of the heating patch.

[0020] Figure 2 This is a trend chart of the effect of iron powder of different sizes on the temperature of the heating patch.

[0021] Figure 3 Temperature change curves of different heating patches, (a) 40℃ heating patch, (b) 45℃ heating patch.

[0022] Figure 4 HE staining of testicular tissue sections of mice on the 7th and 60th days after being treated with different heating patches.

[0023] Figure 5 Changes in fertility rates of mice on days 7 and 60 after being treated with different heat patches. DETAILED DESCRIPTION

[0024] The present invention has developed a self-heating patch that can be used for controllable contraception in male animals. Different heating patches are made by changing the ratio of ingredients to adjust the heating temperature, and placed on the testicles to heat them to different degrees, thereby achieving reversible contraception. The inventors explored the effects of the size of iron powder and the ratio of ingredients on the heating temperature through orthogonal experiments, and explored the effects of different heating patches on spermatogenesis and fertility of male mice.

[0025] The preferred embodiments of the present invention will be described in detail below in conjunction with examples. It should be understood that the following examples are provided only for the purpose of illustration and are not intended to limit the scope of the present invention. Those skilled in the art may make various modifications and substitutions to the present invention without departing from the purpose and spirit of the present invention.

[0026] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

[0027] Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources.

[0028] Example 1

[0029] 1. The influence of different ingredient ratios on the temperature of the heating patch

[0030] Take a 25 mL beaker, add iron powder, activated carbon, sodium chloride, and diatomaceous earth according to the ratio in Table 1 and stir evenly, finally add water and continue stirring, and use an infrared thermal imager to monitor and record the temperature change.

[0031] Table 1

[0032]

[0033] like Figure 1 As shown, when the ingredient ratio is 5.9g iron powder, 4.0g activated carbon, 3.0g sodium chloride, 1.5g diatomaceous earth and 2.2mL water, the temperature rises to a maximum temperature of 70.6°C in 8 minutes, and then decreases; when the ingredient ratio is 5.9g iron powder, 6.0g activated carbon, 3.0g sodium chloride, 1.5g diatomaceous earth and 2.2mL water, the temperature rises to a maximum temperature of 78.4°C in 4 minutes, and then drops sharply, and the final temperature stabilizes at around 36.0°C; when the ingredient ratio is 5.9g iron powder, 4.0g activated carbon, 5.0g sodium chloride, 1.5g diatomaceous earth and 2.2mL water, the temperature rises to a maximum temperature of 79. .0℃, and then decreased; when the ingredient ratio was 5.9g iron powder, 4.0g activated carbon, 3.0g sodium chloride, 3.0g diatomaceous earth and 2.2mL water, the temperature rose to a maximum temperature of 71.7℃ in 8 minutes, and then decreased and finally stabilized at around 42.0℃; when the ingredient ratio was 11.8g iron powder, 4.0g activated carbon, 3.0g sodium chloride, 1.5g diatomaceous earth and 2.2mL water, the temperature rose to a maximum temperature of 81.4℃ in 4 minutes, and then decreased; when the ingredient ratio was 5.9g iron powder, 4.0g activated carbon, 3.0g sodium chloride, 1.5g diatomaceous earth and 5.0mL water, the heating patch had no obvious temperature change. The above results show that increasing the proportion of iron powder is beneficial to increasing the maximum temperature of the heating patch; increasing the proportion of diatomaceous earth is beneficial to improving the thermal insulation of the heating patch; a large increase in the proportion of water is not conducive to the heating of the heating patch; an appropriate increase in the proportion of sodium chloride and activated carbon is beneficial to increasing the temperature of the heating patch, but the thermal insulation is poor.

[0034] 2. Effect of iron powder particle size on temperature

[0035] Take a 25 mL beaker, add 5.9 g of iron powder, 4 g of activated carbon, 3 g of sodium chloride, 1.5 g of diatomaceous earth and 2.2 mL of water respectively and stir evenly, then use an infrared thermal imager to monitor and record the temperature change, where the particle size of the iron powder is shown in Table 2.

[0036] Table 2

[0037]

[0038] like Figure 2 As shown in the figure, the heating patch made of 10.0μm iron powder slowly heated up to a maximum temperature of 54.3℃ in 12 minutes, then slowly decreased and stabilized at around 43℃; the heating patch made of 1.0μm iron powder quickly heated up to a maximum temperature of 82.6℃ in 6 minutes, then dropped sharply; the heating patch made of 50.0μm iron powder heated up to a maximum temperature of 70.6℃ in 8 minutes, then dropped; the heating patch made of 0.2μm iron powder quickly heated up to a maximum temperature of 80.2℃ in 4 minutes, then dropped sharply; the heating patch made of 0.5μm iron powder heated up to a maximum temperature of 80.9℃ in 8 minutes, then dropped. After comprehensively considering various factors such as heating rate and temperature stability, the results show that 10.0μm iron powder has the best effect in making heating patches.

[0039] 3. Make heating patches with different temperatures

[0040] Based on the above results, 10μm iron powder was selected and the proportions of other ingredients were adjusted to produce heating patches with the following temperatures for subsequent male mouse contraceptive studies:

[0041] (1) Ingredients of 40℃ heating patch: 3.0g iron powder, 1.1mL water, 0.4g activated carbon, 0.3g sodium chloride, 3.0g diatomaceous earth;

[0042] (2) Ingredients of 45℃ heating patch: 4.0g iron powder, 1.5mL water, 1.0g activated carbon, 0.8g sodium chloride, and 2g diatomaceous earth.

[0043] According to the inventors' previous research, 15 minutes of 43°C heat therapy on mouse testicles can achieve effective and reversible contraception. In the present invention, the effects of 40°C and 45°C heating patches on mouse testicular function, spermatogenesis and fertility were evaluated. The 40°C and 45°C heating patches were placed on the testicles of male mice for 20 minutes, and thermal images were collected every 60 seconds using an infrared thermal imager (e.g. Figure 3 shown).

[0044] Contraceptive studies include contraceptive reversibility studies and fertility studies:

[0045] (1) Study on the reversibility of contraception: Male mice treated with the heating patch were killed on the 7th and 60th days. The testicles and epididymis were collected at each time point and stored in a -80°C refrigerator for subsequent studies such as tissue sections.

[0046] like Figure 4As shown in the figure, the testicles of mice treated with the 40℃ heating patch were partially damaged on the 7th day, and partial apoptosis and reduction of spermatocytes and sperm cells in seminiferous tubules were observed; the testicles of mice treated with the 45℃ heating patch showed degenerative changes on the 7th day, and all apoptosis of spermatocytes and sperm cells was observed. Over time, the testicular damage of mice treated with the 40℃ and 45℃ heating patches gradually recovered, and the testicular structure almost returned to normal after the 60th day.

[0047] (2) Fertility measurement: The fertility index of male mice was measured on the 7th and 60th day after the treatment with the heat patch. Each male mouse was kept in the same cage with two female mice for 7 days. After mating, the female mice were separated from the male mice. Pregnant mice were observed every two days to determine the time of delivery. The number of pups was recorded after birth.

[0048] like Figure 5 As shown in the figure, compared with the control group, the fertility rate of mice treated with the 40°C heating patch decreased to 30% on the 7th day, and its fertility rate on the 60th day recovered to 89%, indicating that this heating patch cannot achieve effective contraception in mice. The fertility index of mice treated with the 45°C heating patch dropped to 0 on the 7th day, and its fertility rate on the 60th day recovered to 75%, indicating that this heating patch can achieve 100% effective and reversible contraception in mice.

Claims

1. Application of a self-heating patch in male animal contraception, the self-heating patch being made of iron powder, water, activated carbon, sodium chloride and diatomaceous earth.

2. The use according to claim 1, characterized in that: The raw material ratio of the self-heating patch is: 3.0-5.0 g of iron powder, 1.1-1.9 mL of water, 0.4-1.0 g of activated carbon, 0.3-0.8 g of sodium chloride, and 2.0-3.0 g of diatomaceous earth.

3. The use according to claim 1, characterized in that: The raw material ratio of the self-heating patch is: 3.0 g iron powder, 1.1 mL water, 0.4 g activated carbon, 0.3 g sodium chloride, and 3.0 g diatomaceous earth.

4. The use according to claim 1, characterized in that: The raw material ratio of the self-heating patch is: 4.0 g iron powder, 1.5 mL water, 1.0 g activated carbon, 0.8 g sodium chloride, and 2.0 g diatomaceous earth.

5. The use according to claim 1, characterized in that: The raw material ratio of the self-heating patch is: 5.0 g iron powder, 1.9 mL water, 0.75 g activated carbon, 0.5 g sodium chloride, and 2.0 g diatomaceous earth.

6. The use according to any one of claims 1 to 5, characterized in that: The particle size of the iron powder is 0.2-50 μm.

7. The use according to claim 6, characterized in that: The particle size of the iron powder is 10 μm.

8. The use according to claim 1, characterized in that: The application is to place the self-heating patch on the testicles for contraception in male animals.

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