CN108066413A - The carcinous mucolytic effect of Mgrtol standardized and antineoplastic new usage - Google Patents

Abstract

The invention discloses the mucolysis effect of Mgrtol standardized and the antitumor actions of its pharmaceutical composition.Mgrtol standardized can effectively dissolve carcinous mucus, and with antitumor action, Mgrtol standardized, which combines conventional chemotherapy, can improve chemosensitivity.Prolonged application Mgrtol standardized good security, no obvious adverse reaction.

Description

The carcinous mucolytic effect of Mgrtol standardized and antineoplastic new usage

Technical field

The present invention relates to a kind of autonomic drug, more particularly to a kind of autonomic drug and its drug for treating mucilage secretion type tumour The application of combination, belongs to pharmaceutical technology field.

Background technology

Several Kinds of Malignancy has muciparous characteristic, such as alimentary canal myxoadenocarcinoma, signet ring cell cancer, ovarian mucinous Gland cancer, appendix myxoadenocarcinoma, pseudodmyxoma peritonei, malignant mesothelioma etc..Mucous secretion type tumour is more easy to that chemoresistance occurs, and controls Therapeutic effect is bad, prognosis is poor, especially signet ring cell cancer.Patient's life in 5 years of Colon and rectum signet ring cell cancer and peritonaeum metastatic carcinoma Rate only 12% is deposited, and 5 years survival rates of non-myxomous tumour are up to 50%.

Jelly sample ingredient is mainly mucin in mucus, and mucin is a kind of macromolecular of polydispersion（1000 kDa）, bag Containing several glycoprotein monomers to differ in size（100-10000 kDa）.Single glycoprotein unit is polymerize by forming glycosidic bond, is sticked Disulfide bond related cross-links are formed by enzymatic reaction or pH variation oxidations between albumen.It is different according to compactness, it can be by mucus point To be low（It is soft）, it is middle and high（Firmly）Three types.

Mgrtol standardized is the oral soft capsule for the fat-soluble volatile oil production extracted in Myrtaceae category eucalyptus leaves Preparation, main component is eucalyptol, limonene, australene.Mgrtol standardized is mainly used in respiratory disease at present Treatment, including nasosinusitis, chronic bronchitis etc..Mgrtol standardized dissolving mucus and antitumor action there is no to grind both at home and abroad Study carefully.

The present invention is to chance in clinical practice, and mucus is apparent during taking orally the corrective surgery of Mgrtol standardized Thin, mobility enhancing, convenient for suctioning out, operating difficulty substantially reduces, and complete resection rate improves, and separately has diagnosis late period myxoadenocarcinoma And after the patient of intestinal obstruction takes Mgrtol standardized, cooperation conventional therapy means can effectively alleviate intestinal obstruction.Faced based on such Bed phenomenon, experiment in vitro and the Mgrtol standardized dissolving mucus reduction operation for having carried out Mgrtol standardized dissolving mucus are difficult Degree and the Clinical Exploration of Mgrtol standardized combined chemotherapy or targeted therapy, find Mgrtol standardized can in vitro, in vivo it is molten Mucus is solved, operating difficulty is reduced, and has certain antitumor action.

The content of the invention

The present invention is directed to propose mucolysis effect and its medicine group of the Mgrtol standardized in mucilage secretion type tumour The antitumor action of conjunction.

The present inventor has found the mucilage secretion type tumor patient of oral Mgrtol standardized in clinical practice, and symptom can be bright Aobvious to improve, operating difficulty reduces, and complete resection rate improves.Based on such clinical picture, Mgrtol standardized can dissolve carcinous glutinous Liquid plays the role of certain antitumor and raising chemosensitivity.

In certain embodiments, mucilage secretion type tumour is pseudodmyxoma peritonei；

In certain embodiments, mucilage secretion type tumour is Colon and rectum signet ring cell cancer；

In certain embodiments, pharmaceutical composition combines capecitabine for Mgrtol standardized；

In certain embodiments, pharmaceutical composition combines S-1 for Mgrtol standardized；

Thus the present inventor has carried out inside and outside checking test, obtain following technical solution：

At room temperature, 600 mg Mgrtol standardizeds and 10 ml cancer row mucus interaction in vitro 30 minutes, you can observe apparent glutinous Liquid dissolves, and mobility increases phenomenon.

Mucilage secretion type tumor patient, preoperative application Mgrtol standardized 2 weeks（600 mg twice daily, take orally）, can be bright It is aobvious to reduce tumor load, operating difficulty is reduced, reduces organ removal（Such as spleen）, and improve complete resection rate.

Mucilage secretion type patients with relapse of malignant tumor takes orally 5 FU 5 fluorouracil based chemotherapy medicine（Such as S-1, capecitabine）, combine mouth 600 mg of Mgrtol standardized is taken, twice daily, chemosensitivity can be improved, delay tumour progression.

600 mg of Mgrtol standardized vivo applications twice daily, continues 6 months or more good securities, and nothing is apparent not Good reaction, blood routine, biochemistry, electrolyte check Non Apparent Abnormality, the heart, lung, liver, kidney, etc. major organs function Non Apparent Abnormality.

Specific embodiment

The present invention has studied the effect of cancer row mucolytic and its pharmaceutical composition of Mgrtol standardized by internal and external test Antitumor action, be once specific embodiment, technical scheme and technique effect be further explained and illustrated, But protection scope of the present invention is not limited to the embodiment.It should be pointed out that come for those of ordinary skill in the art It says, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to the protection of the present invention Scope, therefore the protection domain of patent of the present invention should be determined by the appended claims.

Following embodiment Plays myrtol uses Germany POHL BOSKAMOP（The big pharmaceutical factories of Bao Shijia）Production Gelomyrtol Forte（Gelomyrtol Forte）.

Embodiment

（One）The carcinous mucus experiment of Mgrtol standardized dissolution in vitro

About 30 ml of mucous tissue in pseudodmyxoma peritonei abdominal cavity of patients is taken in art, is divided into 3 equal portions, is respectively put into 3 50 ml In sterile centrifugation tube, number 1,2,3.2 300 mg/ Mgrtol standardized enteric softs are extracted with 5 ml asepsis injectors Intracapsular liquid is added in No. 3 centrifuge tubes；1 300 mg/ Mgrtol standardized enteric soft is extracted with 5 ml asepsis injectors Intracapsular liquid is added in No. 2 centrifuge tubes；No. 1 centrifuge tube is blank control group, is not added with any substance.Cover tightly three centrifuge tube pipes Lid, acutely shakes mixing, when incubation 2 is small at room temperature.Observe mucus viscosity, mobility variations.After incubation, in 4 °C, 3000 rpm are centrifuged 10 minutes, suction out supernatant, compare the volume and quality of supernatant, ingredient in mass spectral analysis supernatant.

Result of the test：

1. homogenizing after being incubated at room temperature 30 minutes as it can be seen that Mgrtol standardized group mucus substantially dilutes, stickiness reduces, mobility Enhancing, and 600 mg Mgrtol standardizeds groups are apparent compared with 300 mg Mgrtol standardized groups.

2. mass spectral analysis is shown, compared with the control group, Mgrtol standardized group substance is homogeneous, and molecular weight is small, and chain length is shorter.

（Two）The preoperative applying clinical example of Mgrtol standardized

Mgrtol standardized treatment mucous secretion type clinical tumor observation 8, good security, satisfactory effect.

1. general information

8 patient's pathological diagnosis mucilage secretion type tumours are clear and definite, treat row operative treatment.Wherein male patient 4, female patient 4 Example, the median age 56 years old, pseudodmyxoma peritonei 2, Colon and rectum signet ring cell cancer 2, mucous ovarian cancer 2, stomach signet ring is thin Born of the same parents' cancer 1, appendix myxoadenocarcinoma 1.

2. therapy

Oral Mgrtol standardized, 600 mg/ times, twice a day.

3. observation of curative effect

Curative effect is with observation mucus distribution, the relation of hardness and organ, surgery excision difficulty, tumor clearance degree, hand in art The index evaluations such as art time, blood loss volume during the operation.

4. safety evaluation

Safety evaluation is mainly patient main suit, and blood routine, blood biochemistry, electrolyte monitor, the heart, lung, Liver and kidney function monitoring etc..

5. treatment results

Find that tumor load is reduced compared with preoperative evaluation in 8 patient's arts, knurl body softening, operating difficulty reduces.Intraperitoneal mucus sticks Property decline, mobility rise, can completely be suctioned out through vacuum extractor.Knurl body and organ adhesion are loose, can blunt separation, complete Under the premise of preserving normal organ, fully erased tumour and mucous tissue.

6. typical case

Patient, poplar ××, man, 37 years old, diagnosis pseudodmyxoma peritonei more than 2 years, CT showed mucus tumor tissues tight spleen, Boundary is unclear.Preoperative oral Mgrtol standardized 2 weeks, twice daily, 600 mg every time.On June 18th, 2016 operative treatment, art Middle discovery peritoneal cancer index 32 divides（Total score 39 is divided）, mucinous neoplasms diffusivity is distributed in entire abdominal cavity, wraps up spleen.It performed the operation It is found in journey, tumour substantially softens, and part mucous tissue directly can completely suction out through vacuum extractor, success blunt separation spleen Surface mucus tumor tissues, fully erased tumour and mucous tissue, post-surgical cell subtract degree of going out and score 0 point（Total score 3 is divided, 0 point of finger It is visible by naked eyes tumor tissues）.

（Three）Mgrtol standardized combined chemotherapy applying clinical example

Mgrtol standardized combination chemotherapy mucous secretion type tumor post-operation patients with recurrent clinical observation 10, security is good It is good, satisfactory effect.

1. general information

10 patient's pathological diagnosis mucilage secretion type tumours are clear and definite, wherein male patient 3, female patient 7, the median age 53 Year, pseudodmyxoma peritonei 3, mucous ovarian cancer 3, Colon and rectum signet ring cell cancer 2, stomach signet ring cell cancer 1, appendix glue Liquid gland cancer 1.

2. therapy

Oral Mgrtol standardized, 600 mg/ times, twice a day, and Combined with Oral S-1,60 mg/ times, twice a day or Ji Xi His shore, 1.0-1.5 g/ times, twice a day.

3. observation of curative effect

Main detection patients symptomatic relief situation, Imaging examination, blood serum tumor markers variation.Imaging observation index includes Tumor size, density, blood supply and perienchyma's relation etc.；Blood serum tumor markers observation index include CEA, CA125, CA199, CA153 etc..

4. safety evaluation

Safety evaluation is mainly patient main suit, and blood routine, blood biochemistry, electrolyte monitor, the heart, lung, Liver and kidney function monitoring etc..

5. treatment results

10 Chemotherapy in Patients sensibility are remarkably reinforced, tumor mass reduction, and tumor markers declines, and tumour progression slows down, patient Ordinary circumstance greatly improves.

6. model case

（1）Patient, clock ××, female, 53 years old, diagnosis low level myxoadenocarcinoma postoperative recurrence, oral Mgrtol standardized, 600 Mg/ times, twice a day, combine gemcitabine, 1.0-1.5 g/ times twice a day, is treated more than two months, it is seen that pelvic cavity, spleen swell Knurl is obviously reduced, and patient's ordinary circumstance improves.

（2）Patient, Mr. Wang, female, 54 years old, diagnosis pseudodmyxoma peritonei in 2010, row cytoreductive art, postoperative oral S- 1 maintaining treatment, effect are good.Tumor recurrence in 2013, row cytoreductive art add abdominal thermal infusion chemotherapy, and postoperative oral S-1 is maintained Treatment, effect are fine.It recurs again within 2015, takes orally S-1 chemotherapy, effect is poor, adds and is taken orally with Mgrtol standardized, 600 mg/ Secondary, twice a day, patient tumors marker declines apparent.

Claims (5)

1. the application of Mgrtol standardized and its main component in mucilage secretion type tumour.

2. Mgrtol standardized as described in claim 1 and its main component is characterized in that：Mgrtol standardized and its master Ingredient is wanted, including eucalyptol, limonene, australene etc. the application in mucilage secretion type tumour.

3. the application of Mgrtol standardized as described in claim 1 and its main component in mucilage secretion type tumour, special Sign is：Mgrtol standardized and its main component are in treatment alimentary canal myxoadenocarcinoma, signet ring cell cancer, ovarian mucinous gland Application in cancer, appendix myxoadenocarcinoma, pseudodmyxoma peritonei, malignant mesothelioma etc..

4. comprising Mgrtol standardized active ingredient compositions the application in mucilage secretion type tumour.

5. purposes of the Mgrtol standardized active component in anti-tumor medicine is prepared.