CN1087526A - A Gan goes anticancer preparation prescription and technology - Google Patents

Abstract

The present invention is EXD-7-oxabicyclo (2,2,1) heptane-2,3-dicarboxylic anhydride, claims the compound preparation of norcantharidin (OHD) again, and it is made up of OHD, twenty grass or its extract, can add an amount of Colla Corii Asini to improve curative effect in compound recipe.Be used for treating the liver inflammation and antitumor, owing to detoxifcation, the hepatoprotective effect of Radix Glycyrrhizae, reduced the toxic and side effects of OHD significantly, make the OHD oral dose, by 15-45mg/ day bringing up to 75mg/ day or higher, improved the effect of anticancer, leukocyte increasing, raise immunity extremely significantly.

Description

A Gan goes anticancer preparation prescription and technology

EXD-7-oxabicyclo (2,2,1)-dicarboxylic anhydride (OHD) claims norcantharidin again.It is that international first has the anticarcinogen of function of increasing leukocyte, cell to cancer has relative selection inhibition with normal cell, can be when killing and wounding cancerous cell the human body immunity improving ability, its curative effect height, the effect of paying is low, clinically be used for treating treatment hepatocarcinoma, the esophageal carcinoma, gastric cancer, the low disease of leukocyte, also can or be used for combined chemotherapy as premedicate.

But the clinical application oral dose of OHD is 15-45mg/ day only, reaches symptoms such as the part patient produces vomiting, feels sick, dizziness are just arranged 30mg/ day.Surpass 45mg/ day, it is even more serious that its poison is paid effect.According to OHD hepatocellular acute injury be studies have shown that in addition, OHD truly has the acute injury harm to use to mouse liver, behind the mouse peritoneal injection OHD, though small dose group is not found pathological changes, but middle dosage group has been found obvious pathology change of shape, and heavy dose of group is found serious hepatic necrosis, damages by can be observed various widely cell component under Electronic Speculum, it is in morphologic variation, is very similar to the hepatic injury due to the carbon tetrachloride.Though this explanation OHD toxicity decreases than cantharidin, but eliminate, clinical application must strictly be controlled dosage, so the strictness of OHD oral dose is limited in the low-level of 15-45mg/ day, more strictly speaking, the oral dose of OHD is limited in the more low-level of 15-30mg/ day.

Pharmacological evaluation proves that OHD concentration can significantly improve the ability of killing and wounding cancerous cell in the increasing blood.So the effect of paying of above-mentioned poison has seriously limited the further raising of OHD curative effect.

The inventor finds, adds an amount of Radix Glycyrrhizae or its extract in OHD, as extractum, sweet stroke of glucin, enoxolone and sodium salt thereof etc., can reduce the poison of OHD effectively to pay effect, makes the OHD oral dose bring up to 75mg/ day or higher.Pharmacological evaluation proves that Radix Glycyrrhizae and glycyrrhizin have liver protection effect, can obviously alleviate cytolipin change and downright bad, alleviates matter inflammatory reaction between tissue, suppresses the hepatic fibrosis hypertrophy, thereby reduces the liver cirrhosis incidence rate, promotes liver cell regeneration.It has protective effect to the hepatic injury that carbon tetrachloride etc. causes, can prevent to be hindered and the generation of hepatocarcinoma by the liver harm due to the chemical carcinogens.Oral Radix Glycyrrhizae or glycyrrhizin are treated acute chronic hepatitis all better curative effect; Radix Glycyrrhizae is to multiple drug intoxication, and interior metabolism product poisoning, bacteriotoxin poisoning etc. all have better curative effect.Its detoxifcation mechanism is: glycyrrhizin has adsorption to poisonous substance, has reduced the absorption of poisonous substance and detoxifies; Adrenal gland's skin hormone-like effect of enoxolone can improve the regulating action of hypophysis one adrenal system and detoxifies; Behind the poisonous substance chemical combination of glucuronic acid that generates after the Radix Glycyrrhizae hydrolysis and hydroxyl or carboxyl and detoxify.Analyze from chemical constitution, these three kinds of detoxifcation modes can both work to OHD, and the liver protection effect of Radix Glycyrrhizae especially prevents that hepatic injury is even more important when improving its curative effect large dose oral administration OHD.

The inventor finds, in OHD, add Radix Glycyrrhizae or its extract, as extractum or glycyrrhizin, compound preparations such as enoxolone and sodium salt thereof are because of its detoxifcation, liver protection effect, reduce the toxicity of OHD, made the OHD oral dose bring up to 75mg/ day or higher clinically, obviously improved the anti-cancer ability of OHD, leukogenic effect and immunologic function have obviously improved the clinical efficacy of OHD.

This is because Radix Glycyrrhizae has antitumor action, and enoxolone and glycyrrhizin derivative all have inhibitory action to ehrlich carcinoma such as mice and sarcoma, and glycyrrhizin can suppress the yoshida sarcoma of subcutaneous transplantation; Glycyrrhizin, liquiritin can produce in the morphology rat ascites hepatocarcinoma and mice ehrlich ascites cell and change; Feed polyoxy biphenyl to mice and can cause hepatic injury and hepatocarcinoma, if taking glycyrrhizin simultaneously then shows preventive effect, to the super cancer HIV (human immunodeficiency virus) (Human Immunodeficiency Virus), glycyrrhizin has inhibitory action to it, and Radix Glycyrrhizae all has inhibition and preventive effect to kinds of tumors in a word; The glycoside of non-enoxolone unit glycoprotein can hinder macrophage premunition information to behind the mouse mainline, so have immunologic function in addition; Enoxolone energy anti-inflammatory, antiallergic; From Radix Glycyrrhizae carry flavonoid glycoside or glycoside unit can spasmolytic and anti-convulsion and the antiulcer of bursting; Glycyrrhizin can increase bile secretion and suppress the red matter increase of gallbladder etc., so because the collaborative compatibility effect of each medicine in OHD and the Radix Glycyrrhizae compound preparation, making drug effect is not stack, but raising extremely significantly.

Owing to contain protein and 18 seed amino acids in the Colla Corii Asini up to 67.33%, also have 27 kinds of trace element in addition, have the erythrocyte of raising and hemoglobin, promote the effect of hemopoietic function; The expansion blood capillary enlarges blood volume, reduces whole blood viscosity and the effect of blood vessel wall permeability; Increase the effect of serum calcium.Show as hemostasis clinically, enrich blood, enriching yin and nourishing kidney, defying age and the effect of raising immunologic function, the anti-width of cloth penetrate damaging action.

The inventor thinks, adds an amount of Colla Corii Asini in OHD, Radix Glycyrrhizae compound preparation, forms OHD, Radix Glycyrrhizae, Colla Corii Asini compound preparation, and to improving the OHD anti-tumor activity, it should be favourable rising white and exempt from function.

The present invention is applicable to treatment hepatitis and antitumor.

Embodiment one, oral norcantharidin sheet (production of Beijing the 4th pharmaceutical factory), and every day three times, each 15mg has syndromes such as nauseating, vomiting, dizziness.

Embodiment two, oral norcantharidin sheet, and every day three times, each 25mg, and take with 2g liquorice beverage decocting liquid simultaneously, took continuously six days, there is not the reaction of the effect of paying syndrome.

Embodiment three, oral norcantharidin sheet, every day three times, each 20mg, take with 2g Leptoradix Ginseng decocting liquid, produce the symptom of feeling sick, continued to take in second day and pay an effect sx in the back of taking medicine for the third time, after using the 2g Radix Glycyrrhizae extract instead and taking, remission disappears at last.

Embodiment four, and the norcantharidin sheet, after each 20mg takes with 3g Fructus Lycii decocting liquid, has nauseating symptom generation after for the third time at every day three times.

Embodiment five, claim Radix Glycyrrhizae 40g, add decocting liquid, filter, add the heating of 0.45gOHD and 60g Colla Corii Asini and dissolve, last simmer down to 540ml, divide six days oral, do not see malaise symptoms.

Claims (6)

1, the present invention adds an amount of Radix Glycyrrhizae and extract thereof in norcantharidin, as the compound preparation of extractum, glycyrrhizin, enoxolone or its sodium salt composition.

2, according to claim 1, it is characterized in that detoxifcation, hepatoprotective, anticancer, characteristics such as liter is white, immunity with Radix Glycyrrhizae and extract, reduce the poison of OHD to pay effect, improve clinical tolerance dosage and the curative effect of OHD significantly.

According to claim 1,2, it is characterized in that 3, adding Colla Corii Asini in this compound recipe should be favourable to the curative effect that improves this compound recipe, but is not the key component of compound recipe.

4, according to claim 1,2, it is characterized in that, can add medicines such as Radix Ginseng, Fructus Lycii, Radix Glehniae in this compound recipe, to reducing the toxicity of OHD, improve the clinical tolerance dosage of OHD, no positive effect, event adds simply or multi-flavor tonification medicine, or does not add, and does not play a major role in this compound recipe.

5,, it is characterized in that compound recipe can be used for treating hepatitis or as anticarcinogen according to claim 1,2,3,4.

6, according to claim 1,2,3,4,5, it is characterized in that this compound recipe preparation process routinely, can be made into different dosage form, as electuary, oral liquid, membrane, unguentum, tablet or capsule etc.