Oxygen isolation type photodynamic therapy device

Abstract

When the oxygen isolation type photodynamic therapy device is used, the light-transmitting oxygen isolation type equipment covers the skin lesion surface of a patient to form an oxygen isolation layer, the tissue oxygen concentration of the epidermal layer and the dermal superficial layer of the patient can be reduced, and therefore the singlet oxygen photochemical generation rate of the area is reduced, and the photodynamic therapy effect is improved. The level of photochemical pain reaction caused by singlet oxygen during treatment of a patient is reduced; meanwhile, the method is cooperated with a light modulation technology, so that the singlet oxygen accumulation damage ratio of the targeted tissue and the non-targeted tissue can be further improved. Meanwhile, target cells of the erythema are located on capillary walls, target cells of skin precancerous lesions are located near a basal layer, and the oxygen concentration of the places is higher than that of an epidermal layer, so that the target selectivity of photodynamic therapy can be improved; the material can be used for hypoxia photodynamic therapy of nevus flammeus, skin precancerous lesions and other skin diseases.

Description

Technical Field

[0001] This invention belongs to the field of medical device technology, and in particular relates to an oxygen-isolated photodynamic therapy device. Background Technology

[0002] Photodynamic therapy (PDT) is a novel method for treating port-wine stains and precancerous skin lesions. This method uses specific wavelengths to irradiate the lesion site, activating photosensitizers accumulated in the lesion tissue. Utilizing the selective temporal and spatial distribution of photosensitizer, light, and tissue oxygen concentrations, a photochemical reaction is triggered to produce singlet oxygen. The selective cumulative concentration distribution of singlet oxygen across different tissues achieves selective damage to target tissues such as blood vessel walls and tumor cells. In other words, the targeting selectivity of PDT depends on the ratio of the cumulative concentration of singlet oxygen between the target and non-target tissues.

[0003] However, due to the presence of numerous free nerve endings within the skin tissue, distributed throughout the entire body and primarily concentrated near the basal layer of the epidermis and the papillary layer of the dermis, specifically in the epidermis, axons lose their myelin sheath upon entering the epidermis, exposing their branches and traversing between epidermal cells, especially forming terminals below the granular layer and stratum corneum. In the dermis, they are mainly located in the papillary layer, often distributed alongside skin appendages (such as hair follicles and sweat glands). Most free nerve endings originate from thin-diameter myelinated (Aδ) fibers and unmyelinated (C) fibers, with Aδ fibers responsible for rapid pain and cold sensations, and C fibers responsible for slow pain, temperature, and itch sensations. In hairless skin (such as fingertips, lips, and palms), they are more densely distributed at the dermal-epidermal junction, participating in fine tactile discrimination; in hairy skin, free nerve endings are distributed around hair follicles, forming a network that is sensitive to hair movement. The chemical stimulation of nerve endings by singlet oxygen leads to severe therapeutic pain, significantly hindering patient adherence to treatment. In terms of the administration of photosensitizers, there are two main methods: intravenous administration and transdermal administration.

[0004] During photodynamic therapy (PDT) for port-wine stains, the photosensitizer is injected intravenously and then enters the capillary network through the bloodstream, diffusing into the surrounding epidermis. Due to the delayed diffusion effect, a significant concentration difference of the photosensitizer exists between the blood vessels and the tissue. This difference in oxygen concentration between the inside and outside of the blood vessel wall, and the concentration of the photosensitizer, allows for targeted damage to the blood vessel wall. Patients typically experience pain approximately 10 minutes after phototherapy, at which point the photochemical reaction stimulates nerve endings to the pain threshold. Because the target site for PDT of port-wine stains is the proliferating capillary wall, the targeted damage at this point depends on the ratio of the cumulative singlet oxygen concentration in the capillary wall to that in the epidermis.

[0005] In photodynamic therapy for precancerous skin lesions, a photosensitizer is first applied to the lesion surface and incubated in the dark for 3 to 4 hours before phototherapy. Therefore, a concentration gradient of the photosensitizer exists from the outside in the epidermis. Simultaneously, due to the selective absorption and metabolic differences in cancerous tissue, there is also a concentration difference of photoactive substances produced by the metabolism of the photosensitizer between cancerous and normal cells. During phototherapy, this concentration difference of photoactive substances between cancerous and normal cells can achieve selective targeted damage. Patients typically experience pain immediately after photodynamic therapy for precancerous skin lesions, because the photoactive substances have already distributed within the cells, and the photochemical reaction can stimulate nerve endings to the point where pain is perceived.

[0006] Existing photodynamic therapy dosage adjustments mainly include photosensitizer concentration, treatment time, irradiance, and drug administration light interval, but do not include methods for regulating oxygen concentration in skin tissue or suppressing pain. Summary of the Invention

[0007] To overcome the shortcomings of existing photodynamic therapy in oxygen regulation, this invention provides an oxygen-isolated photodynamic therapy device. By combining oxygen isolation with light modulation, it can reduce pain response and targeted damage when treating skin diseases such as port-wine stains and precancerous lesions.

[0008] An oxygen-isolated photodynamic therapy device includes an illumination component and an oxygen-isolated material adhered to the epidermal layer of the tissue to be treated; The treatment beam emitted by the lighting component passes through the oxygen-isolating material and enters the tissue to be treated to perform photodynamic therapy on the tissue. Oxygen-isolating materials are used during photodynamic therapy to isolate the epidermis from the atmosphere, preventing atmospheric oxygen from diffusing through the epidermis into the damaged tissue.

[0009] Furthermore, when the dynamic viscosity of the oxygen-isolating material is less than 200,000 centistokes, the photodynamic therapy device also includes an adhesive layer and a light-transmitting layer; The adhesive layer has a hollow structure, and the hollow part is used to fill the oxygen isolation material. At the same time, the light-transmitting layer covers the adhesive layer and the oxygen isolation material, and together with the adhesive layer, they form a dam structure to prevent the oxygen isolation material from detaching from the epidermal layer of the tissue to be treated during photodynamic therapy.

[0010] Furthermore, the adhesive layer is composed of non-woven fabric, elastic fabric, silicone, or pressure-sensitive adhesive.

[0011] Furthermore, the light-transmitting layer is composed of a material with high light transmittance and low oxygen permeability.

[0012] Furthermore, the light-transmitting layer is made of polyvinylidene chloride, cyclic olefin copolymer / polymer, or ethylene. It is composed of ethylene alcohol copolymers.

[0013] Furthermore, the oxygen-isolating material is a liquid material or an elastic solid material.

[0014] Furthermore, when the oxygen barrier material is a liquid material, the oxygen barrier material is high-viscosity dimethyl silicone oil, polydimethylsiloxane, or liquid paraffin.

[0015] Furthermore, when the oxygen barrier material is an elastic solid material, the oxygen barrier material is elastic silicone.

[0016] Furthermore, the therapeutic beam emitted by the lighting component is a pulsed beam.

[0017] Furthermore, the thickness of the oxygen barrier material is 1~500μm, wherein when the thickness of the oxygen barrier material is 100μm, the light transmittance of the oxygen barrier material is not less than 90%.

[0018] Beneficial effects: 1. This invention provides an oxygen-isolated photodynamic therapy device. In use, by covering the patient's skin lesion surface with a light-transmitting oxygen-isolated material to form an oxygen-isolated layer, the tissue oxygen concentration in the epidermis and superficial dermis can be reduced, thereby reducing the photochemical generation rate of singlet oxygen in the area and reducing the level of photochemical pain response caused by singlet oxygen during treatment. At the same time, this invention, in conjunction with light modulation technology, can further improve the ratio of cumulative singlet oxygen damage to targeted and non-targeted tissues.

[0019] 2. This invention provides an oxygen-isolated photodynamic therapy device. It uses an oxygen-isolated material to block the transdermal oxygen supply pathway to the epidermis, significantly reducing the oxygen concentration within the epidermis. Since the rate of intracellular photochemical reactions is approximately positively correlated with the product of the concentrations of light, oxygen, and photosensitizer within the cell, the significant decrease in oxygen concentration in the epidermis leads to a corresponding decrease in the rate of photochemical reactions, thereby reducing the damaging effect of singlet oxygen photochemistry on epidermal cells. Because the target cells for port-wine stains are located in the capillary walls, and the target cells for precancerous skin lesions are located near the basal layer, where oxygen concentrations are higher than in the epidermis, this invention improves the targeting selectivity of photodynamic therapy and can be used for hypoxic photodynamic therapy of skin diseases such as port-wine stains and precancerous skin lesions. Attached Figure Description

[0020] Figure 1 Exploded view of the assembly of an oxygen-isolated photodynamic therapy device; Figure 2 This is a cross-sectional view of the assembly of an oxygen-isolated photodynamic therapy device. Figure 3A cross-sectional view of the spatial distribution of oxygen concentration in the lesion tissue with skin depth at the start of existing photodynamic therapy; Figure 4 A cross-sectional view of the spatial distribution of oxygen concentration in the lesion tissue with skin depth at the start of oxygen-isolated photodynamic therapy; Figure 5 This is a time-varying graph showing the light modulation and average oxygen concentration in the lesion tissue as a function of light irradiation in oxygen-isolated photodynamic therapy. In the diagram, the light-transmitting layer is 1, the adhesive layer is 2, and the oxygen-isolating material is 3; the stratum corneum is ①, the stratum lucidum is ②, the granular layer is ③, the stratum spinosum is ④, the basal layer is ⑤, the nerves and blood vessels are ⑥, and the cross-section of the oxygen-isolating photodynamic therapy device assembly is ⑦. Detailed Implementation

[0021] To enable those skilled in the art to better understand the present application, the technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the accompanying drawings.

[0022] like Figure 1 As shown, the present invention provides an oxygen-isolated photodynamic therapy device, which can improve the targeted therapeutic effect of photodynamic therapy on skin diseases and reduce pain caused by photochemical reactions; specifically, the present invention includes an illumination component and an oxygen-isolated material adhered to the epidermal layer of the tissue to be treated. The treatment beam emitted by the lighting component passes through the oxygen-isolating material and enters the tissue to be treated to perform photodynamic therapy on the tissue. Oxygen-isolating materials are used during photodynamic therapy to isolate the epidermis from the atmosphere, preventing atmospheric oxygen from diffusing through the epidermis into the damaged tissue.

[0023] Furthermore, the oxygen-isolating material is preferably a liquid material, such as high-viscosity dimethyl silicone oil, polydimethylsiloxane, or liquid paraffin, and has high viscosity and low oxygen solubility or diffusion coefficient to maximally delay oxygen passage. Alternatively, an elastic solid material, such as highly elastic silicone, can be used. When the dynamic viscosity of the oxygen-isolating material is higher than 200,000 centistokes, the high viscosity of the liquid material can maintain its shape, eliminating the need for a light-transmitting layer. When the dynamic viscosity of the oxygen-isolating material is lower than 200,000 centistokes, the photodynamic therapy device further includes an adhesive layer and a light-transmitting layer. The adhesive layer has a hollow structure, and the hollow portion is used to fill the oxygen-isolating material, which has low oxygen permeability and high light transmittance. Simultaneously, the light-transmitting layer covers the adhesive layer and the oxygen-isolating material, forming a dam structure with the adhesive layer to prevent the liquid oxygen-isolating material from flowing freely on the surface of the lesion, thus preventing the oxygen-isolating material from detaching from the epidermal layer of the treated tissue during photodynamic therapy.

[0024] like Figure 2As shown, the oxygen-isolated photodynamic therapy device of the present invention can achieve a good match with the contour of the skin lesion tissue by custom processing an irregular structure that is consistent with the shape of the skin lesion.

[0025] The thickness of the oxygen-barrier light-transmitting dressing is 1~500μm, preferably 10~200μm. Simultaneously, the oxygen-barrier material has high transmittance for therapeutic light; preferably, when the thickness of the oxygen-barrier layer is 100μm, the transmittance is not less than 90%.

[0026] The light-transmitting layer is made of a material with high light transmittance and low oxygen permeability. Preferably, it can be polyvinylidene chloride, cyclic olefin copolymer / polymer, or ethylene. Vinyl alcohol copolymers, etc.; preferably, the thickness is 5~100μm.

[0027] The adhesive layer can be composed of non-woven fabric or elastic fabric, silicone, and pressure-sensitive adhesive to form a dam structure between the adhesive layer and / or the light-transmitting layer, preventing the oxygen-isolating material from detaching from the lesion during photodynamic therapy and preventing atmospheric oxygen from entering the skin through the epidermis.

[0028] like Figure 3 The image shows the spatial distribution of oxygen concentration in the lesion tissue with skin depth at the start of existing photodynamic therapy. At this point, as the depth away from the skin surface increases, the tissue oxygen concentration first decreases, and as the depth increases and the tissue gets closer to the dermal reticular capillary network, the tissue oxygen concentration gradually increases.

[0029] like Figure 4 As shown, this is a spatial distribution diagram of oxygen concentration in the lesion tissue with skin depth at the beginning of oxygen-isolated photodynamic therapy. At this time, since there is no transdermal oxygen supply to the epidermis, its oxygen supply mainly comes from the diffusion of oxygen concentration from the capillary network of the dermis. Therefore, the oxygen concentration of the stratum corneum is the lowest, and the tissue oxygen concentration gradually increases with the increase of the depth away from the skin surface.

[0030] Since free nerve endings are mainly located in the epidermis and the epidermal-dermal junction, and the epidermis is a non-target tissue, reducing the oxygen concentration in the epidermis can reduce the photochemical reaction rate of the epidermis, thereby reducing the photochemical stimulation of free nerve endings by singlet oxygen and reducing the patient's pain.

[0031] Based on this, the method of using the oxygen-isolated photodynamic therapy device of the present invention is as follows: Before photodynamic therapy, the device is adhered to the surface of the skin lesion, and the oxygen-isolated material covers the entire surface of the skin lesion. This can isolate the epidermis from the atmosphere, preventing oxygen in the atmosphere from diffusing into the epidermal layer of the skin lesion through the epidermal layer, so that the oxygen supply of the epidermis, basal layer and papillary dermis comes from the oxygen supply of the capillaries.

[0032] To further enhance the rate difference of photochemical reactions between targeted and non-targeted tissues, Figure 5 This study demonstrates the modulation method of oxygen-isolated photodynamic therapy and the temporal distribution of the average oxygen concentration in the lesion tissue at corresponding times with varying light exposure. Since the rate of photochemical reactions is approximately positively correlated with the product of the concentrations of light, oxygen, and photosensitizer within the cells; since there are differences in oxygen and photosensitizer concentrations from high to low inside and outside the blood vessel walls during photodynamic therapy for port-wine stains; and since there are differences in the concentration of photoactivated substances between targeted and non-targeted cells during photodynamic therapy for precancerous skin lesions; when light is applied, the photochemical reaction rate within the targeted tissue is higher, making it easier to establish a difference in photochemical reaction rate between the targeted and non-targeted tissues. To further improve the rate of oxygen consumption in the photochemical reaction between targeted and non-targeted tissues of the skin, pulse modulation is preferred during photodynamic therapy. This involves alternating between turning the light on and off, and stopping the light treatment after a period of time to allow oxygen to diffuse from the capillaries to the surrounding tissues and achieve a new balance between oxygen diffusion and metabolism. This approach can balance the significant decrease in the rate of photochemical reaction caused by oxygen consumption.

[0033] Preferably, considering that it takes about 1 to 10 seconds for oxygen to diffuse 100 μm inside the tissue, the light-off time is preferably 0.5 to 20 seconds; at the same time, in order to balance the overall phototherapy time, the light-on time is preferably 0.5 to 10 seconds.

[0034] In summary, the present invention provides an oxygen-isolated photodynamic therapy device, which has the following advantages compared with existing photodynamic therapy methods: 1. Reduced photochemical pain. Before phototherapy, an oxygen-isolating, light-transmitting dressing is applied to the surface of the patient's skin lesions. This oxygen-isolating material has low oxygen transmittance and high light transmittance, which isolates the epidermis from the atmosphere, preventing atmospheric oxygen from diffusing into the lesion tissue. Therefore, during photodynamic therapy, this invention reduces the oxygen concentration in the epidermis by using the oxygen-isolating material, thereby reducing the rate of singlet oxygen photochemical generation in the patient's epidermis and superficial dermis, thus reducing the pain caused by photochemical stimulation of nerve endings due to singlet oxygen generation during treatment.

[0035] 2. High targeting selectivity. Photodynamic therapy damages individual cells within the target tissue, and the rate of intracellular photochemical reactions is approximately positively correlated with the product of intracellular light, oxygen, and photosensitizer concentrations. Oxygen supply to skin tissue, particularly the epidermis, includes two main pathways: transdermal and capillary oxygen supply. When the transdermal oxygen supply pathway is interrupted, the oxygen concentration within the epidermis significantly decreases, thereby reducing the rate of photochemical reactions and the damaging effect of singlet oxygen photochemistry on epidermal cells. Furthermore, the target cells for port-wine stains are located in the capillary walls, and the target cells for precancerous skin lesions are located near the basal layer, thus enhancing the targeting selectivity of photodynamic therapy.

[0036] Of course, the present invention may have other various embodiments. Without departing from the spirit and essence of the present invention, those skilled in the art can make various corresponding changes and modifications according to the present invention, but these corresponding changes and modifications should all fall within the protection scope of the appended claims.

Claims

1. An oxygen-isolated photodynamic therapy device, characterized in that, Includes lighting components and oxygen-barrier material adhered to the epidermis of the tissue to be treated; The treatment beam emitted by the lighting component passes through the oxygen-isolating material and enters the tissue to be treated to perform photodynamic therapy on the tissue. Oxygen-isolating materials are used during photodynamic therapy to isolate the epidermis from the atmosphere, preventing atmospheric oxygen from diffusing through the epidermis into the damaged tissue.

2. The oxygen-isolated photodynamic therapy device as described in claim 1, characterized in that, When the dynamic viscosity of the oxygen-isolating material is less than 200,000 centistokes, the photodynamic therapy device also includes an adhesive layer and a light-transmitting layer; The adhesive layer has a hollow structure, and the hollow part is used to fill the oxygen isolation material. At the same time, the light-transmitting layer covers the adhesive layer and the oxygen isolation material, and together with the adhesive layer, they form a dam structure to prevent the oxygen isolation material from detaching from the epidermal layer of the tissue to be treated during photodynamic therapy.

3. The oxygen-isolated photodynamic therapy device as described in claim 2, characterized in that, The adhesive layer is composed of non-woven fabric, elastic fabric, silicone or pressure-sensitive adhesive.

4. The oxygen-isolated photodynamic therapy device as described in claim 2, characterized in that, The light-transmitting layer is made of a material with high light transmittance and low oxygen permeability.

5. The oxygen-isolated photodynamic therapy device as described in claim 2 or 4, characterized in that, The light-transmitting layer is made of polyvinylidene chloride, cyclic olefin copolymers / polymers, or ethylene. It is composed of ethylene alcohol copolymers.

6. The oxygen-isolated photodynamic therapy device as described in claim 1, characterized in that, The oxygen-isolating material is a liquid material or an elastic solid material.

7. The oxygen-isolated photodynamic therapy device as described in claim 6, characterized in that, When the oxygen barrier material is a liquid material, the oxygen barrier material is high-viscosity dimethyl silicone oil, polydimethylsiloxane, or liquid paraffin.

8. The oxygen-isolated photodynamic therapy device as described in claim 6, characterized in that, When the oxygen barrier material is an elastic solid material, the oxygen barrier material is elastic silicone.

9. The oxygen-isolated photodynamic therapy device as described in claim 1, characterized in that, The therapeutic beam emitted by the lighting component is a pulsed beam.

10. The oxygen-isolated photodynamic therapy device as described in claim 1, characterized in that, The thickness of the oxygen barrier material is 1~500μm, wherein when the thickness of the oxygen barrier material is 100μm, the light transmittance of the oxygen barrier material is not less than 90%.

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