Application of high-concentration oxygen as and / or in preparation of medicine for treating retinopathy of premature infant

Abstract

The invention belongs to the technical field of medicines, and discloses an application of high-concentration oxygen as and / or in preparation of a premature infant retinopathy treatment medicine. According to the method, the proliferation efficiency of new vessels in OIR can be efficiently inhibited by utilizing high-concentration oxygen (45%), and the proliferation efficiency is 60% or above. The blood vessel reconstruction efficiency of a blood vessel-free area in the OIR can be promoted to be 15.5% by utilizing high-concentration oxygen (45%). According to the invention, the development of deep blood vessels in OIR can be obviously promoted by utilizing oxygen with relatively high concentration. According to the invention, the situation that the relapse of new vessels after the inhalation of high-concentration (45%) oxygen is stopped is not observed in an experiment by utilizing the high-concentration oxygen.

Description

Technical Field

[0001] The invention belongs to the field of medical technology, and in particular to the use of relatively high concentration oxygen as and / or in the preparation of a drug for treating retinopathy of prematurity. Background Art

[0002] Retinopathy of Prematurity (ROP) is an eye disease involving the development of retinal blood vessels in premature infants, which is more common in premature infants with lower birth weight. Since the lungs, cardiovascular system, and nervous system of premature infants are not fully developed and their autonomous oxygen supply capacity is insufficient, oxygen therapy is widely used as an auxiliary treatment for premature infants. Studies have shown that oxygen therapy is crucial to improving the survival rate of premature infants. However, the "Guidelines for the Treatment of Oxygen and the Prevention and Treatment of Retinopathy in Premature Infants (Revised Edition)" points out that unreasonable use of oxygen greatly increases the risk of ROP. During oxygen therapy for premature infants, arterial oxygen partial pressure and transcutaneous oxygen saturation should be closely monitored. At different levels of respiratory support, the arterial oxygen partial pressure should be maintained at 50-80 mmHg and the transcutaneous oxygen saturation should be maintained at 88-93% with the lowest oxygen volume fraction. When it is higher than the target value, the oxygen volume fraction (oxygen concentration) should be gradually reduced in time. Although the guidelines point out that standardized oxygen use can significantly reduce the occurrence of ROP in premature infants, some premature infants still inevitably develop ROP during oxygen therapy.

[0003] The disease progression of ROP can be divided into two main stages: (1) the avascular stage. After premature infants receive long-term oxygen therapy, the dissolved oxygen in the retinal tissue fluid increases, resulting in the obstruction of peripheral retinal blood vessel development and the formation of an avascular zone. (2) the neovascularization stage. As development proceeds, the retinal tissue in the avascular zone will face the problem of ischemia and hypoxia. The hypoxic state will trigger the activation of multiple downstream signaling pathways that promote angiogenesis, leading to excessive proliferation of abnormal blood vessels, and ultimately causing serious problems such as vitreous hemorrhage and retinal detachment. Since existing treatments have different limitations, there is an urgent need to explore more new treatment strategies.

[0004] 1.2 Existing technologies and defects related to the present invention

[0005] Currently, the main treatments for ROP include laser photocoagulation and anti-VEGF therapy. Laser photocoagulation is the standard treatment for ROP, which reduces retinal hypoxia by destroying the avascular retinal area, thereby reducing the production of downstream vascular factor VEG. The side effects of this method cannot be ignored: it causes retinal damage, loss of peripheral vision, and cannot be used for multiple treatments. Anti-VEGF therapy has large individual differences in effect and is prone to recurrence, requiring more follow-up and repeated treatments, which greatly increases the risk of ocular and systemic complications. Since these methods all have different limitations, there is an urgent need to explore new treatment strategies to provide more treatment options for clinical practice.

[0006] Based on the disease characteristics and pathological mechanism of ROP, existing treatment methods cannot fundamentally solve the problem of retinal hypoxia, and therefore the treatment effect is poor and prone to recurrence, which brings great economic burden to patients and society. Therefore, it is urgent to explore new treatment strategies to provide more treatment options for clinical practice. Summary of the invention

[0007] The purpose of the present invention is to overcome the deficiencies in the prior art and provide a method for using relatively high concentration oxygen as and / or in preparing a drug for treating retinopathy of prematurity.

[0008] The technical solution adopted by the present invention to solve its technical problem is:

[0009] The invention discloses a use of relatively high concentration oxygen as and / or in the preparation of a drug for treating retinopathy of prematurity.

[0010] The invention discloses a use of relatively high concentration oxygen as and / or in the preparation of a medicine for inhibiting the proliferation of neovascularization in retinopathy of prematurity.

[0011] Furthermore, the drug can effectively inhibit the proliferation of new blood vessels in retinopathy of prematurity by more than 60%;

[0012] Alternatively, there was no recurrence of neovascularization after cessation of higher concentration oxygen inhalation.

[0013] A use of relatively high concentration oxygen as and / or in the preparation of a drug for promoting vascular reconstruction in avascular areas in retinopathy of prematurity.

[0014] Furthermore, the drug can promote the vascular reconstruction efficiency of the avascular area in retinopathy of prematurity at 15.5%.

[0015] A use of relatively high concentration oxygen as and / or in the preparation of a drug for promoting the development of deep blood vessels in retinopathy of prematurity.

[0016] Furthermore, the relatively high concentration of oxygen is an oxygen concentration of 45% by volume or more.

[0017] Furthermore, the medicine is an inhalant.

[0018] Furthermore, the drug is used by inhaling a relatively high concentration of oxygen.

[0019] Furthermore, the time of inhaling higher concentration oxygen is 1-2 days;

[0020] Alternatively, higher concentrations of oxygen may be given with an oxygen mask or nasogastric tube.

[0021] The advantages and positive effects achieved by the present invention are:

[0022] 1. The present invention utilizes relatively high concentration of oxygen to effectively inhibit the proliferation of new blood vessels in OIR by more than 60%.

[0023] 2. The present invention utilizes a relatively high concentration of oxygen to promote the vascular reconstruction efficiency of the avascular area in OIR to 15.5%.

[0024] 3. The present invention utilizes relatively high concentration of oxygen to significantly promote the development of deep blood vessels in OIR.

[0025] 4. The present invention utilizes a relatively high concentration of oxygen and no recurrence of neovascularization was observed in the experiment after stopping the inhalation of the relatively high concentration (45%) of oxygen. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 Schematic diagram of the model construction of oxygen-induced retinopathy (OIR) model in the present invention;

[0027] Figure 2 The figure shows the vascular lesions in the retina of OIR mice treated with 45% oxygen for two days; A: treatment time, grouping and evaluation index of OIR mice; B: representative pictures of the retina of each group of mice; C: statistics of the area of ​​new blood vessels and avascular areas in the retina of each group of mice; the percentage of new blood vessels in OIR-P17 mice without 45% oxygen treatment (referred to as OIR-P17) is 7.68%, while the percentage of new blood vessels in OIR-P17 mice treated with 45% oxygen (referred to as 45% O2-OIR-P17) is 3.05%. The percentage of avascular areas in OIR-P17 mice is 29.45%, while the percentage of avascular areas in 45% O2-OIR-P17 mice is 24.88%;

[0028] Figure 3The figure shows the development of deep retinal blood vessels in OIR mice of the present invention after two days of 45% oxygen treatment; wherein, A: representative pictures of the retina of mice in each group; B: statistics of the development area of ​​deep blood vessels in the retina of mice in each group; in the OIR-P17 group, the area of ​​deep blood vessels was 16.74% of the area of ​​surface blood vessels, while in the 45% O2-OIR-P17 group, the area of ​​deep blood vessels was 32.75% of the area of ​​surface blood vessels.

[0029] Figure 4 The figure shows the vascular lesions in the retina of the OIR mice of the present invention after two days of 45% oxygen treatment and then 4 days of stopping the treatment; wherein, A: treatment time, grouping and evaluation index of the OIR mice; B: representative pictures of the retina of each group of mice; C: area statistics of the new blood vessels and avascular areas in the retina of each group of mice; the percentage of avascular areas in 45% O2-OIR-P17 mice was 24.88%, and the percentage of avascular areas in 45% O2-OIR-P21 mice was 6.69%; the percentage of new blood vessels in 45% O2-OIR-P17 mice was 3.05%, and the percentage of new blood vessels in 45% O2-OIR-P21 mice was 3.77%;

[0030] Figure 5 Figure 1 is a diagram showing the vascular lesions in the retina of OIR mice treated with 75% oxygen for two days; A: treatment time, grouping and evaluation indexes of OIR mice; B: representative images of the retina of mice in each group; C: statistics of the area of ​​new blood vessels and avascular areas in the retina of mice in each group; the percentage of new blood vessels in OIR-P17 mice without 75% oxygen treatment was 7.68%, while the percentage of new blood vessels in OIR-P17 mice treated with 75% oxygen was 1.58%; the percentage of avascular areas in OIR-P17 mice was 29.45%, while the percentage of avascular areas in 75% O2-OIR-P17 mice was 34.02%;

[0031] Figure 6 The figure shows the vascular lesions in the retina of the OIR mice of the present invention after two days of 75% oxygen treatment and four days of stopping the treatment; wherein, A: treatment time, grouping and evaluation index of the OIR mice; B: representative pictures of the retina of each group of mice; C: area statistics of the new blood vessels and avascular areas in the retina of each group of mice; the percentage of avascular areas in 75% O2-OIR-P17 mice was 34.02%, and the percentage of avascular areas in 75% O2-OIR-P21 mice was 20.14%; the percentage of new blood vessels in 75% O2-OIR-P17 mice was 1.58%, and the percentage of new blood vessels in 75% O2-OIR-P21 mice was 6.47%. DETAILED DESCRIPTION

[0032] The present invention will be further described below in conjunction with the embodiments. The following embodiments are descriptive rather than restrictive, and the protection scope of the present invention cannot be limited by the following embodiments.

[0033] The various experimental operations involved in the specific embodiments are all routine techniques in the art. For parts not specially annotated in this document, ordinary technicians in the art can implement them by referring to various commonly used reference books, scientific and technological literature or related instructions, manuals, etc. before the filing date of this invention.

[0034] The invention discloses a use of relatively high concentration oxygen as and / or in the preparation of a drug for treating retinopathy of prematurity.

[0035] The invention discloses a use of relatively high concentration oxygen as and / or in the preparation of a medicine for inhibiting the proliferation of neovascularization in retinopathy of prematurity.

[0036] Preferably, the drug can effectively inhibit the proliferation of new blood vessels in retinopathy of prematurity by more than 60%;

[0037] Alternatively, there was no recurrence of neovascularization after cessation of higher concentration oxygen inhalation.

[0038] A use of relatively high concentration oxygen as and / or in the preparation of a drug for promoting vascular reconstruction in avascular areas in retinopathy of prematurity.

[0039] Preferably, the drug can promote vascular reconstruction efficiency of avascular areas in retinopathy of prematurity to 80%.

[0040] A use of relatively high concentration oxygen as and / or in the preparation of a drug for promoting the development of deep blood vessels in retinopathy of prematurity.

[0041] Preferably, the relatively high concentration of oxygen is an oxygen concentration of 45% by volume or more.

[0042] Preferably, the drug is an inhalant.

[0043] Preferably, the drug is administered by inhaling a relatively high concentration of oxygen.

[0044] Preferably, the time of inhaling higher concentration oxygen is 1-2 days;

[0045] Alternatively, higher concentrations of oxygen may be given with an oxygen mask or nasogastric tube.

[0046] Specifically, the relevant preparation and detection are as follows:

[0047] The oxygen-induced retinopathy (OIR) mouse model can well simulate the two disease stages of ROP and is a widely used ROP model in basic medical research. Based on the pathogenesis of ROP and our research practice in the OIR model, we found that oxygen has a dual effect in OIR: (1) In the first stage of OIR, the relatively high oxygen in the tissue causes the blood vessels around the central artery and vein to degenerate, forming an avascular zone (also known as a non-perfused zone); (2) In the second stage of OIR, the relatively low oxygen in the tissue causes retinal hypoxia, triggering multiple signal pathways for the proliferation of new blood vessels. If the relative oxygen concentration in the OIR retinal tissue is increased at this stage, the proliferation of new blood vessels will be effectively inhibited.

[0048] Based on the OIR model, a model of ROP disease, when new blood vessels proliferate in OIR, the suckling mice inhaled a higher concentration of oxygen for 48 hours. The results showed that inhaling a higher concentration of oxygen can not only effectively inhibit the proliferation of new blood vessels, but also promote the vascular reconstruction of the avascular zone and the development of deep retinal blood vessels, thereby avoiding the recurrence of new blood vessels. This study shows that higher concentrations of oxygen have a dual effect in OIR / ROP. On the one hand, in the pathogenesis of OIR / ROP, the use of higher concentrations of oxygen is an important factor causing the occurrence of OIR / ROPROP; on the other hand, in the treatment of OIR / ROP, the use of higher concentrations of oxygen can effectively treat ROP and reduce recurrence. The specific results are as follows: After the retina of OIR mice enters the proliferative stage, inhaling a higher concentration of oxygen can not only effectively inhibit new blood vessels, but also promote the development of blood vessels in the avascular zone and the development of deep retinal blood vessels, effectively avoiding the problem of recurrence. This discovery lays the foundation for solving the problem of poor clinical treatment effect and easy recurrence of ROP, and is expected to provide a new treatment option for the clinical treatment of ROP.

[0049] When new blood vessels are observed in OIR mice and treatment is necessary, the suckling mice are allowed to inhale a higher concentration of oxygen for 48 hours. The higher concentration of oxygen mentioned here refers to a higher oxygen concentration than the environment in which the OIR mice are located when the disease occurs. For OIR mice, a normal pressure (the same as atmospheric pressure) oxygen chamber is used to provide air with a set oxygen concentration. The oxygen chamber has an air inlet and an exhaust port. The oxygen concentration sensor in the chamber controls the oxygen concentration. When the oxygen concentration is lower than the set concentration, oxygen will be introduced; when the oxygen concentration reaches the set concentration, the oxygen introduction will be automatically shut down. After the OIR mice inhale high-concentration oxygen for 48 hours, the higher concentration of oxygen environment is removed and the normal oxygen concentration is restored. The time for treatment when new blood vessels appear in OIR mice, which is increased here, refers to the time from the appearance of new blood vessels to the peak of proliferation.

[0050] Specifically:

[0051] Methods for constructing oxygen-induced retinopathy (OIR) models (e.g. Figure 1 ):

[0052] (1) Postnatal 7 (P7) suckling mice are placed in a normal pressure chamber with their mothers, and the oxygen concentration (volume concentration, all of which refer to volume concentration) is set to 75%. They are kept in this environment for 5 days. At this stage, large avascular areas are formed in the retina, also called non-perfused areas;

[0053] (2) At P12 (P12 is the abbreviation for postnatal day 12, Postnatal 12 (P12)), the pups and mothers were returned to a normal environment with an oxygen concentration of 21%. After returning to the normoxic environment, the avascular areas in the retinal tissue will activate downstream pathways related to the proliferation of new blood vessels due to ischemia and hypoxia;

[0054] (3) After being kept in a normoxic environment for 2 days, at P14, new blood vessels in the OIR retina began to proliferate and reached their peak at P17 (P17 is the abbreviation for postnatal day 17, Postnatal 17 (P17)), which is the peak of the disease.

[0055] Neovascularization and avascular area are two important pathological features of the OIR model. Neovascularization (as a percentage of the total retina) and avascular area (as a percentage of the total retina) are two key indicators for evaluating the therapeutic effect of the OIR model. These two indicators are fluorescently labeled using FITC-IB4, which specifically labels endothelial cells. FITC-IB4 is a fluorescent labeling complex composed of fluorescein isothiocyanate (FITC) and lectin IB4 (Isolectin B4), which can specifically display the vascular network, thereby showing the avascular area and neovascularization.

[0056] Steps for staining slides:

[0057] (1) After the mice were over-anesthetized and killed, the eyeballs were removed and fixed with 4% paraformaldehyde at room temperature for 15 minutes;

[0058] (2) Soak the fixed eyeball in 4°C precooled PBS solution for 30 minutes and place on ice.

[0059] (3) Use microscopic instruments to remove the cornea, lens, etc. of the anterior segment of the eyeball.

[0060] (4) The posterior pole of the retina was placed in a drop of ice-cold PBS, the sclera-choroid complex was removed, and the retina was placed in methanol precooled at -20°C for further fixation for 2 hours before staining.

[0061] (5) Before staining, the methanol-fixed retina was washed three times with PBS precooled at 4°C.

[0062] (6) The retina obtained in step (5) was blocked and permeabilized using 0.3% Triton-PBS containing 1% BSA by mass and 0.5% goat serum by volume, and incubated at 4° C. on a shaker for 2 hours.

[0063] (7) Prepare FITC-IB4 solution with a final concentration of 1 ug / mL using 0.3% Triton-PBS, add it to the retina, and incubate overnight at 4°C on a shaker.

[0064] (8) The retina was washed four times with 0.3% Triton-PBS, each time for 1 hour.

[0065] (9) Use antifade mounting medium to mount the stained retina.

[0066] (10) Use a laser scanning confocal microscope to photograph the retina and select the FITC channel.

[0067] (11) Photoshop was used to collect data on the areas of neovascularization and avascular areas in retinal images, and Graphpad was used to process the data.

[0068] The more specific treatments are as follows:

[0069] Example 1

[0070] On the third day after the oxygen-induced retinopathy (OIR) model mice were taken out of the chamber, that is, at P15 (a large number of new blood vessels had appeared at this time), the OIR mice were returned to the normobaric oxygen chamber, and the oxygen concentration of the oxygen chamber was set to 45%. Two days later, the OIR mice were taken out of the chamber and returned to the normal environment, marked as the 45% O2-OIR group. The OIR mice that did not return to the chamber for 45% oxygen treatment were used as the control group, marked as the Control-OIR group. At P17, the retinas of the Control-OIR and 45% O2-OIR groups of mice were stained to observe the proliferation of new blood vessels and avascular areas in the retina.

[0071] The results show (such as Figure 2 and Figure 3 ):

[0072] (1) At OIR-P15, the area of ​​neovascularization was 1.25% of the entire retina, and the area of ​​avascular zone was 35.58% of the entire retina.

[0073] (2) In the Control-OIR-P17 group, the area of ​​neovascularization was 7.68% and the area of ​​avascular zone was 29.45%.

[0074] (3) In the 45% O2-OIR-P17 group, the area of ​​neovascularization was 3.05% and the area of ​​avascular zone was 24.88%.

[0075] (4) Compared with the Control-OIR-P17 group, the proliferation of new blood vessels in the 45% O2-OIR-P17 group decreased by about 60%, and the recovery of the avascular area increased by about 15.5%.

[0076] (5) In the Control-OIR-P17 group, the deep vascular area was 16.74% of the superficial vascular area, while in the 45% O2-OIR-P17 group, the deep vascular area was 32.75% of the superficial vascular area (approximately twice that of the Control group).

[0077] Example 2

[0078] On the third day after the OIR mice were released from the chamber, i.e., at P15 (a large number of new blood vessels had appeared at this time), the OIR mice were returned to the normobaric oxygen chamber, and the oxygen concentration of the oxygen chamber was set to 45%. Two days later, the OIR mice were released from the chamber and returned to the normal environment, marked as the 45% O2-OIR group. Some of the mice in the 45% O2-OIR group were released from the chamber at the time of release (P17), and some were returned to the normoxic environment and continued to be raised for 4 days (P21). The retinas of the 45% O2-OIR-P17 and 45% O2-OIR-P21 groups were stained and stained to observe the proliferation of new blood vessels and avascular areas in the retina.

[0079] The results show (such as Figure 4 ):

[0080] (1) In the 45% O2-OIR-P17 group, the area of ​​neovascularization was 3.05% and the area of ​​avascular zone was 24.88%.

[0081] (2) In the 45% O2-OIR-P21 group, the area of ​​neovascularization was 3.77% and the area of ​​avascular zone was 6.69%.

[0082] (3) Compared with the 45% O2-OIR-P17 group, the retinal neovascularization in the 45% O2-OIR-P21 group was almost unchanged, while the vascular recovery in the avascular zone of the retina increased by about 66.8%. This indicates that even after the cessation of treatment in the 45% oxygen-treated OIR model, not only did a large number of neovascularization no longer occur, but the vascular recovery in the avascular zone was further accelerated.

[0083] Example 3

[0084] On the third day after the OIR mice were released from the chamber, i.e. at P15 (a large number of new blood vessels had appeared at this time), the OIR mice were returned to the normobaric oxygen chamber, and the oxygen concentration of the oxygen chamber was set to 75%. Two days later, the OIR mice were released from the chamber and returned to the normal environment, marked as the 75% O2-OIR group. The OIR mice that were not returned to the chamber for 75% oxygen treatment were used as the control group, marked as the Control-OIR group. At P17, the retinas of the Control-OIR and 75% O2-OIR groups of mice were stained for flat mounts to observe the proliferation of new blood vessels and avascular areas in the retina.

[0085] The results show (such as Figure 5 ):

[0086] (1) At OIR-P15, the area of ​​neovascularization was 1.25% of the entire retina, and the area of ​​avascular zone was 35.58% of the entire retina.

[0087] (2) In the Control-OIR-P17 group, the area of ​​neovascularization was 7.68% and the area of ​​avascular zone was 29.45%.

[0088] (3) In the 75% O2-OIR-P17 group, the area of ​​neovascularization was 1.58% and the area of ​​avascular zone was 34.02%.

[0089] (4) Compared with the Control-OIR-P17 group, the proliferation of new blood vessels in the 75% O2-OIR-P17 group decreased by about 79.4%, and the recovery of the avascular zone decreased by about 13%. This indicates that after 75% oxygen treatment of the OIR model, although the proliferation of new blood vessels was effectively inhibited, the recovery of blood vessels in the avascular zone was also inhibited.

[0090] Example 4

[0091] On the third day after the OIR mice were released from the chamber, i.e., at P15 (a large number of new blood vessels had appeared at this time), the OIR mice were returned to the normobaric oxygen chamber, and the oxygen concentration of the oxygen chamber was set to 75%. Two days later, the OIR mice were released from the chamber and returned to the normal environment, marked as the 75% O2-OIR group. Some of the mice in the 75% O2-OIR group were released from the chamber at the time of release (P17), and some were returned to the normoxic environment and continued to be raised for 4 days (P21). The retinas of the 75% O2-OIR-P17 and 75% O2-OIR-P21 groups were stained and stained to observe the proliferation of new blood vessels and avascular areas in the retina.

[0092] The results show (such as Figure 6 ):

[0093] (1) In the 75% O2-OIR-P17 group, the area of ​​neovascularization was 1.585% and the area of ​​avascular zone was 34.02%.

[0094] (2) In the 75% O2-OIR-P21 group, the area of ​​neovascularization was 6.476% and the area of ​​avascular zone was 20.14%.

[0095] (3) Compared with the 75% O2-OIR-P17 group, the proliferation of new blood vessels in the mouse retina in the 75% O2-OIR-P21 group increased to 300%, and the recovery of blood vessels in the avascular zone of the retina increased by about 40.7%. This indicates that after the cessation of the 75% oxygen treatment OIR model, new blood vessels began to proliferate again.

[0096] In the OIR mouse model, OIR mice were returned to a normal environment from a normobaric oxygen chamber at P12. The oxygen concentration in the normal environment is 21%, which is a relatively lower oxygen concentration than the oxygen concentration in the oxygen chamber. Therefore, new blood vessels appeared in the retina of OIR mice from P12 to P17, and the peak of new blood vessel proliferation was reached at P17.

[0097] Current treatments, such as laser photocoagulation and anti-VEGF therapy, can only temporarily inhibit the proliferation of new blood vessels, are prone to recurrence and require multiple treatments, and cannot promote vascular remodeling in avascular areas.

[0098] In the present invention, a higher concentration of oxygen is used for treatment, that is, at P15 when new blood vessel proliferation occurs, OIR mice are treated with 45% oxygen. The treatment effect is very outstanding. It not only effectively inhibits the proliferation of new blood vessels in the OIR retina (about 60%), but also promotes the vascular reconstruction of the avascular zone in the OIR retina (about 15.5%). In addition, 45% oxygen treatment also promotes the development of deep blood vessels in the OIR retina (about 2 times). What is more worthy of our attention is that after 45% oxygen treatment is stopped for 4 days, new blood vessels no longer recur, and vascular reconstruction in the non-perfused zone is further accelerated. In this process, it is also found that with the increase of the treatment oxygen concentration, such as increasing to 75%, its inhibitory effect on the proliferation of new blood vessels also increases (to 79.4%). This reminds us that we need to pay attention to that when the oxygen concentration increases to 75%, the vascular reconstruction in the avascular zone is hindered; after stopping 75% oxygen treatment, the new blood vessels will recur again. Therefore, it should be noted during the treatment process that the oxygen concentration used for treatment is not the higher the better. The present invention suggests that the oxygen with a volume fraction of 45% is the optimal treatment concentration.

[0099] Although the embodiments of the present invention are disclosed for illustrative purposes, those skilled in the art will appreciate that various substitutions, changes and modifications are possible without departing from the spirit and scope of the present invention and the appended claims. Therefore, the scope of the present invention is not limited to the contents disclosed in the embodiments.

Claims

1. A use of relatively high concentration oxygen as and / or in the preparation of a drug for treating retinopathy of prematurity.

2. Use of relatively high concentration oxygen as and / or in the preparation of a drug for inhibiting the proliferation of neovascularization in retinopathy of prematurity.

3. The use according to claim 2, characterized in that: The drug can effectively inhibit the proliferation of new blood vessels in retinopathy of prematurity with an efficiency of more than 60%; Alternatively, there was no recurrence of neovascularization after cessation of higher concentration oxygen inhalation.

4. Use of relatively high concentration oxygen as and / or in the preparation of a drug for promoting vascular reconstruction in avascular areas in retinopathy of prematurity.

5. The use according to claim 4, characterized in that: The drug can promote the vascular reconstruction efficiency of avascular areas in retinopathy of prematurity at 15.5%.

6. Use of relatively high concentration oxygen as and / or in the preparation of a drug for promoting the development of deep blood vessels in retinopathy of prematurity.

7. The use according to any one of claims 1 to 6, characterized in that: The relatively high concentration of oxygen is an oxygen concentration of 45% by volume or more.

8. The use according to any one of claims 1 to 6, characterized in that: The medicine is an inhaler.

9. The use according to claim 8, characterized in that: The drug is used by inhaling a higher concentration of oxygen.

10. The use according to claim 9, characterized in that: The time for inhaling higher concentration oxygen is 1-2 days; Alternatively, higher concentrations of oxygen may be given with an oxygen mask or nasogastric tube.

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