CN103251650B - Application of roe milk in preparation of medicine used for preventing and treating gastric cancer and precancerous lesion - Google Patents

Application of roe milk in preparation of medicine used for preventing and treating gastric cancer and precancerous lesion Download PDF

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Publication number
CN103251650B
CN103251650B CN201310185038.6A CN201310185038A CN103251650B CN 103251650 B CN103251650 B CN 103251650B CN 201310185038 A CN201310185038 A CN 201310185038A CN 103251650 B CN103251650 B CN 103251650B
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gastric
deer
preparation
precancerous lesion
treasure
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CN103251650A (en
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郑亮
陈寒昱
王媛媛
梅雨玫
李镇
赵太媛
冯进
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Abstract

The invention discloses an application of roe milk in preparation of a medicine used for preventing and treating gastric cancer and precancerous lesions. Roe milk is a milk block taken out form a glandular stomach of a young roe in a lactation period, has sweet taste and natural nature, has the effects of strengthening the spleen and stomach, helping digestion and removing stagnancy as well as building body and prolonging life and can be used for preparing a medicine composition and preparation used for improving the immunity and preventing and treating the gastric cancer and the precancerous lesions.

Description

The purposes of deer treasure in the medicine of preparation prevention and treatment gastric cancer and cercinoma prophase pathologic change thereof
Technical field
The present invention relates to a kind of medicinal active ingredient in the application of preparing in medicine, relate in particular to deer treasure in the application of preparing in medicine, belong to medical technical field.
Background technology
Deer treasure belongs to famous and precious rare medical material, is the infantile dyspepsia piece taking out children river deer glandular stomach from age of sucking.Record according to Compendium of Material Medica, deer treasure is warm in nature, and sweet in the mouth is flat, the effect that have invigorating the spleen and regulating the stomach, dyspepsia and intestinal stasis relieving, braces up energy and delay senility.
Analyze after testing, the protein content of deer treasure reaches 39%, contains 17 seed amino acids such as taurine and threonine simultaneously, and wherein 7 kinds is human body essential amino acid, and content is higher than general milk product, wherein especially high with the content of glutamic acid, proline, valine and lysine; The result of Elements shows, the calcareous content of deer treasure is higher, and every 100 grams of dry powder are containing 959.5mg, the several times that the content of copper, manganese is other food, and content and the milk product of zinc, magnesium are suitable, and deer treasure contains immunoglobulin amount up to 28.5%.
By to studies have shown that of experiment mice, deer treasure can improve the pepsic vigor of mice, and can improve very significantly mice with spleen deficiency serum gastrin content.The mensuration of mouse small intestine propulsion functions is shown, deer treasure can obviously promote small intestinal peristalsis.The tradition of deer treasure is applied as facilitating digestion function and treatment indigestion.
Gastric cancer is one of common malignant tumor, and its sickness rate and mortality rate all occupy the prostatitis of malignant tumor in China.The canceration of gastric epithelial cell is a progressive process, and in the normal experience lasting preventing precancerous lesion of stomach cancer stage for many years, some patient finally can be developed into gastric cancer.Therefore prevention or treatment gastric precancerous lesion, stoping precancerous lesion to be converted into pernicious gastric cancer is an important channel that prevents and treats gastric cancer, for reducing, China's cancer morbidity and patient death rate are significant.The inventor is through research with keen determination, especially find in the research of the therapeutical effect of gastric precancerous lesion and treatment mechanism for deer treasure, deer treasure can be prevented and treated the generation of gastric precancerous lesion and then prevention gastric cancer well, widen the application of deer treasure, also for prevention and the treatment of gastric cancer provide new therapeutic scheme.
Summary of the invention
According to a first aspect of the present invention, provide the purposes of deer treasure in the medicine for the preparation of prevention or treatment gastric precancerous lesion.
According to another aspect of the present invention, the pharmaceutical composition that contains deer treasure is provided, made by active component deer treasure and one or more pharmaceutically acceptable carriers or excipient.
Deer treasure of the present invention can adopt method well known in the art to obtain, the newborn river deer of for example raising and train more than breeding three generations is sucking stomach after river deer milk, especially in abomasum (glandular stomach) meeting, form Off-white solid or semi-solid block, underwent operative is drying to obtain after taking out.
The deer treasure that the present invention specifically adopts is commercially available prod.
In pharmaceutical composition of the present invention, deer treasure can be used as the first activating agent, in pharmaceutical composition, can also contain the second activating agent, and the second activating agent is selected from Radix Codonopsis, the Rhizoma Atractylodis Macrocephalae, Poria, Semen Coicis, Vascular aurantii, Radix Ginseng, the Radix Astragali, Cordyceps mycelium.
The amount of the contained deer treasure in minimum dose unit of pharmaceutical composition of the present invention is 30mg.
Product of the present invention comprises and contains medicine and the health product that relating to of deer treasure prevents and/or treats gastric mucosal precancerous lesions, prevents and treats gastric cancer related application.
The invention still further relates to and prevent and/or treat other mucosa as pharmaceutical composition and the pharmaceutical applications of the precancerous lesion of bladder, cervix uteri, uterus, small intestinal or large intestine, oral cavity, nasopharynx, esophagus etc.
Pharmaceutical composition of the present invention can be made and be suitable for any dosage form that human or animal uses.Route of administration can be intestinal or parenteral route, as: oral, intravenous injection, intramuscular injection, subcutaneous injection, nasal cavity, oral mucosa, eye, lung and respiratory tract, skin, vagina, rectum etc.Form of administration can be liquid dosage form, solid dosage forms or semisolid dosage form.Liquid dosage form can be solution (comprising true solution and colloid solution), Emulsion, microemulsion, suspensoid, injection (comprising aqueous injection, injectable powder and transfusion), eye drop, nasal drop, lotion, liniment etc.; Solid preparation can be tablet (comprising ordinary tablet, enteric coatel tablets, buccal tablet, dispersible tablet, chewable tablet, effervescent tablet, oral cavity disintegration tablet etc.), capsule (comprising hard capsule, soft capsule, enteric coated capsule), granule, powder, micropill, drop pill, suppository, membrane, paster, the agent of gas (powder) mist, spray etc.; Semi-solid preparation can be ointment, gel, paste etc.Preparation can be made ordinary preparation, also can be slow releasing agent, controlled release agent, targeting preparation and various particulate delivery system.
Dosage form of the present invention can be used the usual any method using in pharmaceutical preparation technology to produce, and is not particularly limited.
The inventor adopts chemical carcinogen induction gastric mucosa of rat hyperplasia of prostate/precancerous lesion/stomach malignant cancer model, study the effect that deer treasure suppresses generation evolution, prevention gastric precancerous lesion and the Malignant Gastric carcinogenesis of gastric mucosa of rat hyperplasia of prostate → gastric mucosal precancerous lesions → stomach malignancy that chemical carcinogen two leads, prove that deer treasure can obviously suppress the intestinal epithelial metaplasia of gastric mucosa, alleviate the precancerous lesions such as the atypical hyperplasia of stomach basal cell, reduce gastric tumor growth, reduce generation rate of malignant tumour.Prove that deer treasure has control gastric precancerous lesion, the effect of the pernicious carcinogenesis of prevention stomach.
The present invention proves through rat test, and deer treasure can improve the rat body weight of chemical carcinogen induction, suppresses Gastric Mucosal Cells hypertrophy, reduces the incidence rate of gastric mucosal precancerous lesions atypical hyperplasia, intestinal epithelial metaplasia, reduces stomach malignancy incidence rate.
The specific embodiment
Below in conjunction with specific embodiment, the present invention is described in further detail.
Embodiment 1: the preparation of deer treasure aqueous solution
Effective ingredient deer treasure in the present invention can adopt method well known in the art to obtain, the newborn river deer of for example raising and train more than breeding three generations is sucking stomach after river deer milk, especially in abomasum (glandular stomach) meeting, form Off-white solid or semi-solid block, underwent operative is drying to obtain after taking out.
1. select the newborn river deer of raising and train more than breeding three generations of 12 ages in days to raise with river deer breast bottlefeeding.After three hours, this breast river deer glandular stomach position can touch lump;
2. by newborn river deer anesthesia sterilization, bring aseptic operating room into, be fixed on operating-table, carry out live body operation, cut glandular stomach open, take out Off-white solid or semi-solid block, dry, pulverizing, crosses 200 mesh sieves, obtains and can be used in the deer treasure that the present invention uses.
3. deer treasure aqueous solution dosage: rat dose,equivalent=people one daily dose * 0.018*5 (70 kilograms of calculating of people's standard body weight), 0.5 times of conduct of dose,equivalent is low dose of, and dose,equivalent is middle dosage, and twice is heavy dose of.Deer treasure aqueous solution, to preserve in 4 ℃ of refrigerators, is heated to about 15 ℃ uses when use.
Effective ingredient deer treasure in the present invention also can commercially available prod, below experimental example deer treasure used be commercially available prod.
Experimental example
Grouping: 42 of clean level Wistar male rats, body weight is between 180g-220g.Feed 7 days at laboratory adaptability, room temperature is controlled between 18-25 ℃, show after normal growth that fasting can't help water and weigh for 12 hours again, by randomized and the random district group method of dividision into groups, rat is divided into 8 of blank groups, 34 of model group, adopt MNNG solution freely to drink to model group and close irregular diet modeling, choose at random 2 rats from model group, cut open the belly and get the situation of stomach observation gastric mucosa, confirm after modeling success, 32 rats are divided into model control group, deer treasure small dose group, middle dosage group, heavy dose of group at random, every group each 8.
Gastric precancerous lesion (PLGC) rat modeling: adopt take MNNG as principal element the modeling method modeling of associating additive method.Adopt the free drinking technique of MNNG to coordinate and press down acid, irregular diet and NaTDC, ethanol administration by gavage associating modeling.First MNNG is formulated as to the storage liquid of 1g/L concentration with distilled water, once, lucifuge, stored refrigerated, pack the drinking bottle that posts black lucifuge paper in configuration weekly, freely drinks for rat.Except blank group rat, all the other are respectively organized in rat word material and add the ranitidine hydrochloride with 0.03%, give hungry full alternate nursing, take food 2 days, and fasting 1 day, uses 20mmol/L deoxycholic acid sodium solution with dosage 10mL/kg gavage that afternoon of taking food after 2 days; Fasting that afternoon of 1 day, by 40% ethanol 10mL/kg gavage, continue 16 weeks.Blank group gives equivalent normal saline gavage, common standard word material.The 16th weekend of modeling, from model group rat, randomly draw 2 rats, getting gastric antrum and body of stomach organizes after each one, with conventional haematoxylin one Yihong dyeing, after fixing with 20% formalin, the gastric mucosa of observing 2 rats under light microscopic all has atrophy, and occurs that intestinal and atypical hyperplasia change, to confirm successful duplicating model.
Administration: after modeling 16 weeks, deer treasure aqueous solution is with 25mg/kg, 50mg/kg, 100mg/kg dosage gavage, and every day 1 time, blank group, model control group give 10ml/kg normal saline gavage, and every day 1 time, treatment group administration time is 12 weeks.
HE stained preparation gathers: put to death after rat, cut open the belly and get stomach, take out full stomach from breaking apart from cardia and pylorus 1.5cm, cut full stomach open in greater gastric curvature side, get 0.2 × 2.0cm strip gastric tissue, be placed in rapidly 4% paraformaldehyde solution and fix after 24h, paraffin embedding, standby HE dyeing, the variation of light Microscopic observation gastric mucosa.
Experimental result
1, ordinary circumstance and body weight
Blank group rat expression is freely, energy is good, and happiness is moving flexibly, fur gloss, and diet is normal; Model control group rat lethargy, tired in moving, the in disorder gloss of owing of fur, diet reduces, and medication group rat all has activity and diet in various degree to increase, and body weight increases, fur is owed gloss, and more blank group of rat expression of general state, energy is not good enough, and other performances are better than model control group.
Table 1: experimental rat body weight at 12 weekend changes situation
Group N (only) Body weight (g)
Blank group 8 204.65±10.05
Model control group 8 176.65±6.08*
Deer treasure low dose group 8 194.95±11.56**
Dosage group in deer treasure 8 199.26±10.04***
Deer treasure high dose group 8 198.54±11.71**
Note: with relatively * P < 0.01 of blank group, * * P < 0.05 compared with model control group, * * * P < 0.01.
2, gastric mucosa pathology
(1) perusal
Model group gastric wall in rats is thinner, and elasticity is poor, owes gloss, and without mucus, mucosa is pale asphyxia or canescence, and part mucosa outward appearance is dispersed in petechia and fine grained sample changes; Blank group gastric wall in rats elasticity is good, glossy, and mucous membrane surface is smooth smooth, and coating mucus is more, mucosa pinkiness; The basic, normal, high dosage group of Chinese medicine coat of the stomach elasticity is better, and mucosa is light red or kermesinus, and pleat is relatively dark, and visible a small amount of mucus is adhered to.
(2) HE dyeing microscopic examination
Blank group: gastric epithelial is complete, cellular morphology homogeneous, in lamina propria, body of gland marshalling is tight, a small amount of lymphocyte that sporadically appears, body of stomach and gastric antrum portion have no obvious cell infiltration.
Model control group: gastric mucosa part body of gland atresia, part body of gland occurs back-to-back or is total to wall phenomenon, gastric pits prolongation, and in lamina propria, visible inflammatory cell infiltrates, infiltration can reach muscularis mucosae deeply, the visible lymphocyte of part mucosa is assembled and lymph follicle forms, blood vessel hyperplasia, and gastric antrum portion body of gland arrangement disorder hypertrophy is obvious, basilar part body of gland epithelial proliferation, visible goblet cell, nuclear hyperchromatism is double-core even, has moderate dysplasia and intestinal epithelial metaplasia.
Deer treasure low dose group: gastric mucosa body of gland is arranged relatively neat, cellular morphology is compared with homogeneous, and the boundary of Glandular Epithelium and Gland pipe is clear, the visible atrophy of part body of gland, intestinal, cell infiltration is mainly confined to mucosa shallow-layer, and it is complete that intrinsic body of gland keeps.
Dosage group in deer treasure: body of stomach, gastric antrum portion mucosal inflammation compared with model group, deer treasure is low, high dose group is light, visible edema, hyperemia and epithelium non-viable non-apoptotic cell comes off, lymphocyte and cell infiltration, the visible a small amount of eosinophilic granulocyte of part and neutrophil infiltration under mirror.
Deer treasure high dose group: gastric mucosa epithelium is complete compared with model group, cellular morphology is homogeneous relatively, and the interior body of gland of lamina propria is arranged closeer, a small amount of lymphocyte that sporadically appears, the boundary of Glandular Epithelium and Gland pipe is clear, and cell infiltration is mainly confined to mucosa shallow-layer.
(3) statistics
Deer treasure low dose group is light compared with model group mucosa pathological changes, and atrophic focus scope is little, mild degree, 4 routine glandular epithelium dysplasias (hypertrophy is light, moderate 2 examples, in, severe 2 examples), 5 routine intestinal epithelial metaplasias.In deer treasure, dosage group is light compared with model group mucosa pathological changes, and atrophic focus scope is little, mild degree, 4 routine glandular epithelium dysplasias (hypertrophy is light, moderate 3 examples, in, severe 1 example), 4 routine intestinal epithelial metaplasias.During high dose group mucosa dysplasia and intestinal epithelial metaplasia improve, low dose group is obvious, 3 still have dysplasia (1 moderate, 2 light, moderates), 4 intestinal epithelial metaplasias.Blank group has no dysplasia and intestinal epithelial metaplasia and Mucosal atrophy pathological changes.Model group mucosa pathological changes has no recovery, and has the trend of increasing the weight of, and shows as atrophy kitchen range scope and strengthens, and dysplasia degree increases the weight of (3 of its mild or moderates, 4 of moderates, 1 of severe), and intestinal epithelial metaplasia number of cases increases to 5.
Table 2: experimental rat gastric mucosa at 12 weekend changes situation
Group N Atrophic gastritis Dysplasia Intestinal epithelial metaplasia
Blank group 8 0 0 0
Model control group 8 8 8 5
Deer treasure low dose group 8 8 4 5
Dosage group in deer treasure 8 8 4 4
Deer treasure high dose group 8 7 3 4
Result shows: deer treasure aqueous solution has the gastric precancerous lesion of improvement rat ordinary circumstance, improves body weight, the effect of prevention and treatment gastric precancerous lesion, minimizing Malignant Gastric carcinogenesis rate.

Claims (4)

1. deer treasure is in the purposes for the preparation of preventing and/or treating in the pharmaceutical composition of mucosa precancerous lesion, and wherein mucosa precancerous lesion is gastric precancerous lesion.
2. purposes as claimed in claim 1, wherein in pharmaceutical composition, deer treasure, as unique active component, also contains pharmaceutically acceptable carrier or excipient.
3. purposes as claimed in claim 1, wherein deer treasure, as the first activating agent, also contains the second activating agent in described pharmaceutical composition, and the second activating agent is selected from Radix Codonopsis, the Rhizoma Atractylodis Macrocephalae, Poria, Semen Coicis, Vascular aurantii, Radix Ginseng, the Radix Astragali, Cordyceps mycelium.
4. purposes as claimed in claim 2, wherein pharmaceutical composition is prepared to and is suitable for human or animal and uses dosage form, and described dosage form is selected from solution, Emulsion, suspensoid, injection, tablet, capsule, granule, powder, micropill, drop pill.
CN201310185038.6A 2013-05-20 2013-05-20 Application of roe milk in preparation of medicine used for preventing and treating gastric cancer and precancerous lesion Expired - Fee Related CN103251650B (en)

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