Sodium protoporphyrin production and application

A technology of protoporphyrin sodium and protoporphyrin, applied in the field of medicine, can solve problems such as unreported therapeutic or preventive effects of protoporphyrin, complicated causes, and immune damage of liver cells

Inactive Publication Date: 2008-09-10
王利忠
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] However, the causes of liver injury are very complicated. In addition to acute hepatitis caused by carbon tetrachloride or other hepatotoxic drugs and viral hepatitis caused by hepatitis virus, lymphocytes in the immune system (especially cytotoxic T lymphocytes) The response to antigens can also cause immune damage to liver cells, causing apoptosis of liver cells, and even leading to liver cirrhosis and hepatocellular carcinoma (see, for example, Nelson et al., J. Immunol, 158: 1473-1481; Wong et al. , J. Immunol., 160: 1479-1488)
The mechanism of immune liver injury is different from the liver injury caused by hepatotoxic drugs and viruses. There is still no report that protoporphyrin has a therapeutic or preventive effect on immune liver injury, and there is no report that protoporphyrin has an effect on D-galactosamine. Amine-induced acute liver injury has a therapeutic or preventive effect, so further research is needed to expand the scope of new indications for protoporphyrin, a drug that has been proven to be safe in humans after long-term use
[0004] In addition, although Chen Wenhui et al. (see, Chinese Journal of Pharmaceutical Industry, 31(7): 293-294) proposed an improved method for preparing sodium protoporphyrin, the raw material it needs is pure hemin; The preparation method reported in the literature also uses the high-purity heme used in the laboratory, rather than the industrial heme that is directly extracted from animal blood, whose purity does not meet the laboratory preparation requirements but is much cheaper (for example, see, China Patent application CN1300732A, CN1306002A, CN1450073A, etc.), so it is not suitable for industrial production

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  • Sodium protoporphyrin production and application
  • Sodium protoporphyrin production and application
  • Sodium protoporphyrin production and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] The production method of embodiment 1 protoporphyrin

[0036] 1. Preparation of Crude Protoporphyrin

[0037] Get 100 grams of heme (purchased from Haining Hetianlong Biotechnology Co., Ltd., prepared according to Chinese patent application CN1450073A), add it to 5000 ml of 85% formic acid, and divide 30 g of iron powder within 25 minutes under stirring and heating to reflux. Add five times, then reflux for 20 minutes, cool to room temperature, filter, add 20000ml of 20% ammonium acetate solution to the filtrate, let it stand for 12 hours, precipitate crystals, filter the crystals, dissolve them with 1200ml of 20% ammonia water, then add 30% ammonium acetate solution 2000ml, placed for 12 hours, crystals were precipitated, washed twice with 1200ml of 2% acetic acid, washed three times with 1800ml of water, and dried to obtain 40g of protoporphyrin crude crystals.

[0038] 2. Protoporphyrin dimethyl ester preparation

[0039] Get protoporphyrin crude crystal 100g, add ...

Embodiment 2

[0042] Example 2 Protective effect of protoporphyrin sodium on immune liver damage induced by BCG and lipopolysaccharide

[0043] 1. Experimental Animals

[0044] Wistar rats (body weight 180g-220g, purchased from Zhejiang Provincial Experimental Animal Center) were randomly divided into the following 4 groups, 10 rats in each group: (1) Diammonium glycyrrhizinate group (injection of diammonium glycyrrhizinate, purchased from Jiangsu Zhengdatian Qing Pharmaceutical Co., Ltd.); (2) sodium protoporphyrin group (administration of sodium protoporphyrin by intragastric administration); (3) blank control group; (4) model group.

[0045] 2. Experimental method

[0046] On day 0, in the other 3 groups except the blank control group, 0.2ml BCG polysaccharide nucleic acid injection (purchased from Hunan Jiuzhitang Siqi Biopharmaceutical Co., Ltd. 126 μg / kg body weight) for sensitization; at the same time, the blank control group was injected with an equal volume of normal saline. The...

Embodiment 3

[0052] Example 3 Protective effect of protoporphyrin sodium on acute liver injury induced by D-galactosamine

[0053] 1. Experimental Animals

[0054] Wistar rats (body weight 180g-220g, purchased from Zhejiang Experimental Animal Center) were randomly divided into the following 4 groups, 10 rats in each group: (1) Diammonium glycyrrhizinate group (injection of diammonium glycyrrhizinate, purchased from Jiangsu Zhengda Tianqing Pharmaceutical Co., Ltd.); (2) sodium protoporphyrin group (administration of sodium protoporphyrin by intragastric administration); (3) blank control group; (4) model group.

[0055] 2. Experimental method

[0056] In the diammonium glycyrrhizinate injection group, starting from the 0th day, intraperitoneally injecting 13.5 mg / kg of diammonium glycyrrhizinate into rats for 7 days; in the sodium protoporphyrin group, starting from the 0th day , intragastric administration of protoporphyrin sodium to rats every day, the dosage is 10 mg / kg rats in terms...

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Abstract

The invention relates to applications of protoporphyrin in preparing medicines used for treating or preventing immunological liver injury or D-galatosamine induced acute liver injury; moreover, the invention also relates to a preparation method of the protoporphyrin and the preparations thereof.

Description

technical field [0001] The invention belongs to the technical field of medicine, in particular, the invention relates to the application of protoporphyrin in the preparation of medicines for treating or preventing liver damage, the preparation method of protoporphyrin and its products. Background technique [0002] The chemical name of protoporphyrin (English name Protoporphyrin) is 7,12-divinyl-3,8,13,17-tetramethyl-21H,23H-porphine-2,18-dipropionic acid (7, 12-Diethenyl-3, 8, 13, 17-tetramethyl-21H, 23H-porphine-2, 18-dipropanoic acid). Protoporphyrin is a liver function improving agent extracted and isolated from mammalian blood at first, and it (especially sodium protoporphyrin) has the functions of promoting cell tissue respiration, improving protein and sugar metabolism, and anti-complement fixation. Animal experiments have shown that protoporphyrin has the effect of significantly reducing aminotransferases on liver damage caused by carbon tetrachloride (for example, ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/409A61P1/16C07D487/22
Inventor 朱成钢王利忠
Owner 王利忠
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