A kind of preparation method of 10-hydroxycamptothecin/porphyrin photosensitizer composite preparation

Abstract

The invention provides a preparation method and application of a 10-hydroxycamptothecine / porphyrin photosensitizer composite preparation, relates to a preparation method and application of a porphyrinphotosensitizer composite preparation and aims at solving the technical field of poor survival rate effect of the existing porphyrin compound photosensitizer on cancer cells. The method comprises thefollowing steps of 1, preparing dimerization L-glutamic acid; 2, preparing tetramerization L-glutamic acid; 3, preparing hexameric L-glutamic acid; 4, preparing hexameric glutamic acid bonding porphyrin dimers; 5, preparing the 10-hydroxycamptothecine / porphyrin photosensitizer composite preparation. The 10-hydroxycamptothecine / porphyrin photosensitizer composite preparation is applied to inhibition of the cancer cell survival rate. The 10-hydroxycamptothecine / porphyrin photosensitizer composite preparation can lower the cancer cell survival rate to 10 percent under the condition of the illumination for 40 min.

Description

technical field

[0001] The invention relates to a preparation method of a compound preparation of porphyrin photosensitizer and chemotherapeutic drug 10-hydroxycamptothecin. Background technique

[0002] Porphyrins are essential substances for all organisms to maintain biological activity. Its molecule contains a highly conjugated tetrapyrrole coplanar macrocycle, and there may be central metal atoms such as manganese or iron in the center of the macrocycle. The presence of the macrocyclic conjugated electron system of porphyrins makes their soret and Q bands absorb wavelengths. Therefore, porphyrin compounds have attracted the attention of researchers from all over the world in order to apply them to medical photosensitizers. Due to the special structural characteristics of porphyrin itself, porphyrin has special optical properties. In addition, porphyrin compounds have a special affinity with tumor cells. It can be enriched in large quantities near cancer cells, and can ...

Examples

specific Embodiment approach 1

[0018] Specific embodiment one: This embodiment is a preparation method of a 10-hydroxycamptothecin / porphyrin photosensitizer composite preparation, which is specifically carried out in the following steps:

[0019] 1. Mix 12.4g~14.7g of L-glutamic acid and 100mL~150mL of water evenly, control the stirring speed at 800r / min~1200r / min, stir until L-glutamic acid is completely dissolved, add 16g~20g of acetic anhydride , then heated to 80°C to 90°C, continued to control the stirring speed to 800r / min to 1200r / min, stirred for 30min to 50min, cooled to room temperature, controlled the temperature to -20°C, kept for 12h to 24h, then suction filtered, and used 0 Wash the filter layer with ice water at ℃~4℃, dry it naturally, and then carry out vacuum sublimation separation under the condition of 60℃~80℃ to obtain the sublimated white snowflake crystal product dimeric L-glutamic acid and non-sublimated off-white solid Product amino-protected glutamic acid;

[0020] 2. Mix 50mL~71mL...

specific Embodiment approach 2

[0024] Specific embodiment 2: The difference between this embodiment and specific embodiment 1 is: In step 1, mix 13g of L-glutamic acid and 120mL water evenly, control the stirring speed to 1000r / min, and stir until the L-glutamic acid is completely dissolve. Others are the same as the first embodiment.

specific Embodiment approach 3

[0025] Specific embodiment three: the difference between this embodiment and specific embodiment one or two is that in step two, 61mL of thionyl chloride and 125mg of dimerized L-glutamic acid obtained in step one are mixed uniformly at room temperature and heated to 80°C, keep the reaction conditions and continue the reaction for 3h, and then distill under reduced pressure until no distillate is distilled to obtain the reaction liquid. Others are the same as those in Embodiment 1 or 2.

technical field

[0001] The invention relates to a preparation method of a compound preparation of porphyrin photosensitizer and chemotherapeutic drug 10-hydroxycamptothecin. Background technique

[0002] Porphyrins are essential substances for all organisms to maintain biological activity. Its molecule contains a highly conjugated tetrapyrrole coplanar macrocycle, and there may be central metal atoms such as manganese or iron in the center of the macrocycle. The presence of the macrocyclic conjugated electron system of porphyrins makes their soret and Q bands absorb wavelengths. Therefore, porphyrin compounds have attracted the attention of researchers from all over the world in order to apply them to medical photosensitizers. Due to the special structural characteristics of porphyrin itself, porphyrin has special optical properties. In addition, porphyrin compounds have a special affinity with tumor cells. It can be enriched in large quantities near cancer cells, and can ...

Examples

specific Embodiment approach 1

[0018] Specific embodiment one: This embodiment is a preparation method of a 10-hydroxycamptothecin / porphyrin photosensitizer composite preparation, which is specifically carried out in the following steps:

[0019] 1. Mix 12.4g~14.7g of L-glutamic acid and 100mL~150mL of water evenly, control the stirring speed at 800r / min~1200r / min, stir until L-glutamic acid is completely dissolved, add 16g~20g of acetic anhydride , then heated to 80°C to 90°C, continued to control the stirring speed to 800r / min to 1200r / min, stirred for 30min to 50min, cooled to room temperature, controlled the temperature to -20°C, kept for 12h to 24h, then suction filtered, and used 0 Wash the filter layer with ice water at ℃~4℃, dry it naturally, and then carry out vacuum sublimation separation under the condition of 60℃~80℃ to obtain the sublimated white snowflake crystal product dimeric L-glutamic acid and non-sublimated off-white solid Product amino-protected glutamic acid;

[0020] 2. Mix 50mL~71mL...

specific Embodiment approach 2

[0024] Specific embodiment 2: The difference between this embodiment and specific embodiment 1 is: In step 1, mix 13g of L-glutamic acid and 120mL water evenly, control the stirring speed to 1000r / min, and stir until the L-glutamic acid is completely dissolve. Others are the same as the first embodiment.

specific Embodiment approach 3

[0025] Specific embodiment three: the difference between this embodiment and specific embodiment one or two is that in step two, 61mL of thionyl chloride and 125mg of dimerized L-glutamic acid obtained in step one are mixed uniformly at room temperature and heated to 80°C, keep the reaction conditions and continue the reaction for 3h, and then distill under reduced pressure until no distillate is distilled to obtain the reaction liquid. Others are the same as those in Embodiment 1 or 2.

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