CN106390122A - Oral composition of anticancer chemotherapeutic preparations - Google Patents
Oral composition of anticancer chemotherapeutic preparations Download PDFInfo
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- CN106390122A CN106390122A CN201510465527.6A CN201510465527A CN106390122A CN 106390122 A CN106390122 A CN 106390122A CN 201510465527 A CN201510465527 A CN 201510465527A CN 106390122 A CN106390122 A CN 106390122A
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Abstract
The invention relates to an oral composition of anticancer chemotherapeutic preparations. A formula for the composition comprises active components consisting of chemotherapeutic drugs like taxanes, Omega-3 aliphatic acid, dietary fiber, etc., and further comprises adjuvant components. The gastric-soluble and enteric capsules and sublingual and buccal tablets of the oral composition are used for local or targeted drug delivery for different diseases, greatly improve curative effect and lower toxic and side effect. The oral composition overcomes the problems of toxicity and curative effect of a drug delivery system like an injection. Moreover, an oral dosage form is simpler; the dosage and time of oral administration can be easily adjusted; the treatment concentrations of chemotherapeutic drugs like taxane active substances are easily to regulate and control; and the concentrations of taxanes can be maintained at an effective treatment concentration and be lower than toxic concentration in a treatment period. Compared with taxanes in the dosage form of an injection in the prior art, the oral composition provided by the invention achieves the purposes of long-term administration and continuous treatment; so the impact therapy that treatment should be suspended after a certain treatment course and be resumed after recovery of muscle power.
Description
Technical field
The present invention provides oral chemotherapy kind anti-cancer drugs preparation compositions, and the application in terms of the treatment cancer in digestive system tumor disease such as such as cancer of the stomach and intestinal cancer.
Background technology
Chemotherapy kind anti-cancer drugs have long been used in treating cancer.Such medicine includes (1) alkylating agent：Alkylating agent directly acts on DNA, prevents cancer cell regeneration；(2) antimetabolite：Antimetabolite disturbs the synthesis of DNA and RNA, and such medicine is mainly used in treatment chronic leukemia, breast cancer, oophoroma, cancer of the stomach and colorectal cancer；(3) antitumor antibiotics class：By the effect of inhibitory enzyme and mitosis or change cell membrane and disturb DNA, such medicine is widely used in the treatment to cancer；(4) plant kind anti-cancer drugs：Plant kind anti-cancer drugs include taxane class of anti-cancer agents, are vegetable soda and natural prodcuts, and they can suppress mitosis or the effect of enzyme, thus preventing the necessary protein of cytothesis from synthesizing, are applied to the treatment of multiple carcinomas.
Taxanes medicine injection in chemotherapeutic class is the choice drug of current anticancer chemotherapy.Such medicine includes taxol, Docetaxel, and Cabazitaxel in clinical practice.
Taxol (Paclitaxel, Taxol), also known as PTX, Paclitaxe, Paclitaxe, chemical constitution is as follows：
Taxol is the complicated secondary metabolite of one of Chinese yew genus plants, is also the only a kind of medicine that can promote microtubule polymerization and stably be polymerized micro-pipe being understood at present.Tagging shows, taxol is bonded only in the micro-pipe of polymerization, not with unpolymerized tubulin dimerization precursor reactant.Substantial amounts of micro-pipe can be accumulated in the cell, the accumulation of these micro-pipes disturbs the various functions of cell, particularly makes cell division stop at m period, has blocked the proper splitting of cell after cells contacting taxol.The principle of taxol anticancer is the in-growth cancer cell of selective killing.In 1992 in U.S.'s listing, nineteen ninety-five lists taxol medicine injection in states such as Britain, Japan, and China was in the approval of import in 1997.Prove through clinical application for many years, taxol has significant curative effect to cancer of the stomach, lung cancer, advanced breast cancer, oophoroma, cancer of the esophagus, nasopharyngeal carcinoma, carcinoma of urinary bladder, lymph cancer etc..
Docetaxel (docetaxel, Taxotere) be taxol derivative, its mechanism of action is identical with taxol, is to strengthen tubulin polymerization effect and suppression microtubule depolymerization effect, result in stable non-functional microtubule fasolculus, thus tumoricidal mitosis.In some applications, concentration ratio taxol is high in the cell for Docetaxel medicine, and the holdup time is long in the cell.The chemical molecular formula of Docetaxel is as follows：
Docetaxel injection chemotherapy product has been approved for late gastric cancer in the U.S..
Cabazitaxel (Cabazitaxel), 7 Β, 10 Β-dimethoxy docetaxel, another name:7 Β, 10 Β-dimethoxy docetaxel.The mechanism of anticancer action of Cabazitaxel is similar to Docetaxel with feature, belongs to anti-micro-pipe class medicine.Cabazitaxel by with tubulin binding, promote it to be assembled into micro-pipe, these micro-pipes having assembled can be stoped simultaneously to disintegrate, make microtubule stabilization, and then the mitosis of suppression cell, and the performance of Interphase cells function (interphase cellular functions).The chemical molecular formula of Cabazitaxel is as follows：
Bearing taxanes (taxol, Docetaxel, Cabazitaxel etc.) injection is the choice drug of current anticancer chemotherapy.Although what taxone had proven to current chemotherapeutic most preferably selects medicine, injection formulation now still haves the shortcomings that some are difficult to overcome.First toxic and side effect is big, and the cell of any division of the related killing of system medication of taxanes medicine therefore has certain toxic and side effect.Two is that formulation is single, and the unique formulation of taxanes is injection, produces and using all complex, toxic and side effect performance simultaneously more prominent.Three is to affect the treatment.Using injection, in short-term, the serum-concentration of taxanes is higher than toxic concentration, due to toxic and side effect larger it is impossible to continuous use, affect therapeutic effect.
Content of the invention
In order to solve the above problems, the present invention provides a kind of small toxicity, is easy to oral medication, the chemotherapy kind anti-cancer drugs oral preparation composition of Synergy and attenuation.
The technical solution used in the present invention is：A kind of chemotherapy kind anti-cancer drugs oral preparation composition, active ingredient includes chemotherapy kind anti-cancer drugs, Omega-3 aliphatic acid, dietary fiber and adjuvant.
Described chemotherapy kind anti-cancer drugs include alkylating agents anticarcinogen, anti-metabolism anticarcinogen and antitumor animals and plants composition kind anti-cancer drugs.Described alkylating agents anticarcinogen comprises as Nimustine, BCNU and endoxan.Described anti-metabolism anticarcinogen comprises to deoxygenate fluorine guanosine, how western fluorine bird pyridine 5 '-DFUR, mercaptopurine Ismipur 6-MP, cytarabine, arabinosylcytosine Ara-C, fluorine guanosine, fluorine bird deoxyribonucleoside FNDR, Tegafur, FT-207 FT-207, gemcitabine, gemzar Gemzer, Carmofur, fluorine urine hexylamine HCFU, hydroxycarbamide HU, methotrexate (MTX), amethopterin MTX, UFT, compound Tegafur UFT, ancitabine ancitabine.Described antitumor animals and plants composition kind anti-cancer drugs comprise Irinotecan CPT-11, harringtonine HHRT, HCPT Hydroxycamptotheci, taxane class of anti-cancer agents, TPT Topotecan, vincristine, leurocristine VCR, Teniposide, brave and fierce VM-26, Etoposide, etoposide VP16.
Above-mentioned chemotherapy kind anti-cancer drugs oral preparation composition is it is preferred that described antitumor animals and plants composition kind anti-cancer drugs are taxane class of anti-cancer agents.Described taxane class of anti-cancer agents includes taxol, Docetaxel and Cabazitaxel.In UD, taxane class of anti-cancer agents content is 10～200 milligrams.
Above-mentioned chemotherapy kind anti-cancer drugs oral preparation composition, described Omega-3 aliphatic acid comprises EPA and/or DHA；Described Omega-3 aliphatic acid can be the form of ethyl ester, triglyceride, free acid and salt；The form of described Omega-3 aliphatic acid can be the form that liquid, solid-state or any one can be applied in medical treatment.In UD, Omega-3 content of fatty acid is 100～800 milligrams.When Omega-3 aliphatic acid comprises EPA and DHA, by weight, EPA:DHA is 10:90～90:10.Preferably EPA:The ratio of DHA is about 90:10,80:20,70:30,60:40,50:50,40:60,30:70,20:80,10:90.
Above-mentioned chemotherapy kind anti-cancer drugs oral preparation composition, described dietary fiber includes foodstuff dietary fiber and health care productses dietary fiber；In unit dosage, the content of dietary fiber is 200～2000 milligrams.
Above-mentioned chemotherapy kind anti-cancer drugs oral preparation composition is it is preferred that described dietary fiber includes semen pulicariae shell.
Above-mentioned chemotherapy kind anti-cancer drugs oral preparation composition, described adjuvant includes pharmaceutical carrier；Described pharmaceutical carrier includes D- α-cetomacrogol 1000 succinate, and/or octanoic acid LABRAFIL M 1944CS, and/or capric acid LABRAFIL M 1944CS, and/or list oleic acid sorbitan ester, and/or ascorbyl palmitate, and/or polyoxyethylene olein, and/or polyethylene glycol, and/or absolute ethyl alcohol；In unit dosage, auxiliary agent content is 60～300 milligrams.
Above-mentioned chemotherapy kind anti-cancer drugs oral preparation composition, it is peroral dosage form combinations of the above thing being prepared in capsule shells, or one of combinations of the above thing or two kinds of active ingredients are prepared in different capsule shells respectively, the peroral dosage form simultaneously or asynchronously taken.
Above-mentioned chemotherapy kind anti-cancer drugs oral preparation composition, is the liquid forms that combinations of the above thing is prepared into soft capsule；Or the solid dosage of hard shell capsules or tablet.
The therapeutic action having included taxone single dose in the chemotherapy kind anti-cancer drugs medically applied has been proved to, but inventor herein finds in the composite dosage form invented, because the inhibition cancer cell growth of Omega-3 and immunoregulation effect, chemotherapeutic is even more ideal with Omega-3 combined treatment effect.Further, dietary fiber (as semen pulicariae shell) can delay the absorption of taxol to discharge, and reduces toxic and side effect, and helps regulating intestinal canal system when oral, have certain Synergistic anti-cancer effect simultaneously.Described total effect is to heighten the effect of a treatment, and reduces toxicity.
The application of the present invention is mainly for digestive system tumor such as cancer of the stomach and intestinal cancer (straight colon cancer and the carcinoma of the rectum), and carcinoma of mouth and laryngocarcinoma.Formulation to treatment cancer of the stomach, oral capsule dissolves in stomach and plays the effect of suppression tumour growth；Formulation to treatment intestinal cancer, oral capsule in enteral dissolving and plays the effect suppressing tumour growth；Formulation to treatment carcinoma of mouth and laryngocarcinoma, can be prepared into sustained release lozenge or sublingual sustained release tablets.This formulation, after intestines and stomach dissolving, can be done directly on tumour cell, plays inhibitory action.But due to reasons such as digestive system malabsorption and degradeds, and in formulation Omega-3 aliphatic acid and dietary fiber adjustment effect, the medicine of only very small amount (＜ 5%) can enter blood by intestines and stomach, greatly reduces system application as produced by injection because of the side effect produced by killing to internal proper splitting cell.
Taking the taxol medicine metabolism of oral absorption as a example.First, taxol is subject to malabsorption in intestines and stomach, and only small part can absorb；Second, Omega-3 aliphatic acid and dietary fiber slow down further and limit gastrointestinal absorption；3rd, taxol, to the drug reflux transport protein being distributed in enteron aisle and gall-bladder road, P- glycoprotein (P-gp), is had high affinity, is easily excluded by this mechanism.4th, the taxol of absorption is directly entered liver, and by hepatic metabolism, metabolite is external by courage exclusion.In liver, by the catalytic action of cytochrome P450 (CYP) 2C8, taxol is oxidized to 6- hydroxypaclitaxel (6-hydroxypaclitaxel), and this derivative continues metabolism, and is secreted into bile exclusion.Because mechanism is discharged in above-mentioned metabolism, only have the oral taxanes medicine of 1-4% to be absorbed in blood in this formulation, greatly reduce the toxic and side effect of institute's drug administration.
The scheme of another Synergy and attenuation of the present invention is that application Omega-3 aliphatic acid offsets the toxicity to human body for the taxone further to immune adjustment and the suppression to growth of cancer cells, and increases the curative effect to suppression tumour.In addition, taxone is water insoluble, but it is dissolved in alcohols and esters solvent, therefore the derivative such as Omega-3 fatty acid glycerine three fat and ethyl ester can simultaneously work as dissolving taxone in composite dosage form medicine, increases the effect of bioavilability.
Omega-3 aliphatic acid is eicosapentaenoic acid (EPA, chemical constitution is as follows) and docosahexaenoic acid (DHA, chemical constitution is as follows) to the principle active component of human health.EPA and DHA is that mankind's normal health existence institute is required, but itself can not synthesize, so being referred to as essential fatty acid.
EPA(all-cis-5,8,11,14,17-eicosapentaenoic acid)
DHA(all-cis-4,7,10,13,16,19-docosahexaenoic acid)
The food sources of the Omega-3 aliphatic acid (including EPA and DHA) of nature are the higher fatty acid fish of deep-sea cold water, including salmon, tuna, and mackerel.Omega-3 aliphatic acid exists in certain plants oil, such as Linseed oil and algal oil.Highly purified Omega-3 aliphatic acid can also be purified out from these wholefoods.Highly purified Omega-3 (EPA and DHA) can be prepared into the health products of multi-form.Highly purified Omega-3 aliphatic acid can also be prepared into the chemical species of ethyl ester, such as EPA- ethyl ester and DHA- ethyl ester.The EPA- ethyl ester purifying and DHA- ethyl ester have been prepared to therapeutic dosage forms, and are approved by the fda in the United States for treating high glycerine three fat disease.
The definition of dietary fiber is the edible food composition do not digested and assimilated by digestion, including SNSP, lignin, and indigestible compound sugar and resistant starch.Dietary fiber can provide health care, such as reduces diabetes and cardiopathic risk.Dietary fiber is also proved there is therapeutic action to some pathological reactions and disease, such as can significantly improve or prevent GER, irritable bowel syndrome, room is scorching, the intestinal tract disease such as constipation/diarrhoea and colon cancer.
Dietary fiber and fiber heath-care product include soluble and solvable dietary fiber.Soluble dietary fiber promotes food in the motion of digestive system and to increase stool volume, so being eaten for a long time beneficial to prolonged constipation and the irregular person that defecates.Solvable dietary fiber dissolving forms colloid in aqueous, can help reduce cholesterol and blood sugar level.Dietary fiber is good for health to be it is well known that and being proved in science.FDA (FDA) just advocated the Major Foods with dietary fiber for health and reasonable diet structure when 1998, and pointed out：" taking the content that soluble dietary fiber can reduce T-CHOL in blood for a long time, thus reducing the generation of cardiovascular and cerebrovascular disease ".In addition U.S. FDA allows every part is contained the solvable dietary fiber of 1.7 grams of semen pulicariae shells or the food labeling of 0.75 gram of oat or the solvable dietary fiber of barley is often to eat to reduce cardiac risk.
The food sources of solvable dietary fiber include but is not limited to：Oat wheat bran, roasting oat, oat comprehensively, full paddy barley and dry mushroom barley, and semen pulicariae.This kind of dietary fiber can also be prepared into the health products of multi-form, such as dry powder, tablet and capsule, and every content of such as market sale is the health-caring capsule of 0.85 gram of semen pulicariae shell.Whole meal, comprehensive wheat bran, kernel and various vegetables are all the very good materials of soluble dietary fiber.
Above-mentioned dietary fiber all can be applicable to this formulation, plays Synergistic treatment and drops hypotoxic effect.
In description herein, chemotherapeutic includes all chemotherapeutic as herein described, including taxanes chemotherapy medicine.
In description herein, " EPA " is all-cis-5,8,11,14,17-eicosapentaenoic acid, and " DHA " is all-cis-4,7,10,13,16,19-docosahexaenoic acid.Term EPA and DHA is used for showing free acid, and this kind of aliphatic acid of triglycerides and esterified form, the form except other than triglycerides or esterification is clearly indicated in the text simultaneously.Especially, it should be noted that the form of esterification includes EPA- ethyl ester (ethyl-EPA) and DHA- ethyl ester (ethyl-DHA).EPA and DHA also includes acceptable free acid and soap in medicine.
In description herein, Omega-3 and Omega-3 aliphatic acid have same implication, that is, include the Omega-3 aliphatic acid of active component EPA and DHA.The principle active component of Omega-3 aliphatic acid is EPA and DHA, and its chemical species includes free acid, free hydrochlorate, triglycerides and ethyl ester.
In description herein, taxol includes " active " taxol of form of ownership, including native purified, synthesis, semisynthetic, such as taxol, Docetaxel, Cabazitaxel etc..Taxol also include highly purified (such as from about>99%) or partially purified (such as from about>50%) it is suitable for peroral dosage form, safely and effectively form.
In description herein, one " formulation " or one " dosage " refers to give the active agents of one UD of patient.Active agents include taxol and the Omega-3 aliphatic acid isoreactivity composition of various combination.The illustration of formulation includes tablet, hard shell capsules, and soft capsule includes gel and iquid capsule, suspension, liquid, candy and chewable tablets formulation, emulsus, ice cream shape, ointment shape, and suppository etc.." gel capsule " is any type of topping up soft capsule.Institute's topping up body includes liquid, suspension, solution, gel, and latex etc..
In description herein, peroral dosage form includes capsule (as hard shell capsules and soft capsule), compressing tablet, oral agents, liquid agent, or any type of applicable oral medication formulation.
In description herein, " local is administered " and " target administration " have identical meaning, all refer to active drug composition and are mainly used in focal part, and work in the local treated, for example play therapeutic action for the main of cancer of the stomach in stomach, main for intestinal cancer plays therapeutic action in enteron aisle.
In description herein, the composition invented refers to that the main active that described formulation includes is chemotherapeutic, Omega-3 aliphatic acid and dietary fiber.
In description herein, chemotherapeutic in formulation, what taxol, Omega-3 aliphatic acid and dietary fiber etc. all can be single or compound is referred to as active component.
In description herein, one " patient " or " individual " or " patient " are mammals, a most likely people.Mammal includes, but not limited to the animal waited upon, sport animals, pet (such as cat, dog, horse etc.), Primate, mouse and rat etc..
In description herein, term " cancer in digestive system " refers herein to any malignant tumour being present in digestive system, including cancer of the stomach, the carcinoma of the rectum, colon cancer, laryngocarcinoma, carcinoma of mouth etc..
In description herein, term " treatment " is defined as the treatment measures for certain disease or imbalance, including but not limited to suppresses this kind of disease or imbalance, for example, stops the development of this kind of disease or imbalance；Make this kind of disease or imbalance healing, for example, make patient recovery or recovery；Or recover the pathologic condition caused by from this kind of disease or imbalance, such as stop, prevent or treat the symptom of this kind of disease or imbalance.
In the present invention, the chemotherapy class for the treatment of cancer of the stomach is administered orally anticarcinogen and can be prepared into conventional (non-enteric) capsule, and such capsule is rapidly dissolvable to play direct suppression and killing action with the stomach cancer cell to not yet diffusion in stomach.The preparation method of capsule is within the scope of well-known to those skilled in the art.
In the present invention, the chemotherapy class for the treatment of bowel cancer is administered orally anticarcinogen and can be prepared into capsulae enterosolubilis.Such capsule is insoluble in stomach, but rapidly dissolvable plays direct repression with the bowel cancer to not yet diffusion in enteron aisle.The preparation method of such capsule is within the scope of well-known to those skilled in the art.
In the present invention, the chemotherapy class for the treatment of carcinoma of mouth and laryngocarcinoma is administered orally anticarcinogen and can be prepared into sustained release lozenge or sustained release sublingual tablet.Such sustained release tablets can be done directly on cancer cell thus suppressing or killing the cancer cell in growth.
In the present invention, include chemotherapy kind anti-cancer drugs in capsule, wherein choice drug is taxane class of anti-cancer agents.In described composite dosage form, including taxane class of anti-cancer agents, Omega-3 aliphatic acid, dietary fiber, adjuvant (e.g., pharmaceutical carrier).Taxane class of anti-cancer agents includes taxol, Docetaxel or Cabazitaxel.In UD (with grain as measurement unit, that is, UD refers to a taxanes soft capsule to UD), taxane class of anti-cancer agents content is about 10-200 milligram, about 20-150 milligram, about 40-100 milligram, preferably 40-80 milligram.Omega-3 content of fatty acid is about 100-800 milligram, about 200-600 milligram, about 300-500 milligram, preferably 300-400 milligram.Dietary fiber content is about 200-2000 milligram, about 400-1500 milligram, preferably 500-1000 milligram.Auxiliary agent content is about 60-300 milligram, preferably 100-200 milligram.
In the present invention, the taxanes for the treatment of intestinal cancer is administered orally anticarcinogen and can be prepared into capsulae enterosolubilis.The preparation method of capsulae enterosolubilis is to add additives in capsule formula to make capsule insoluble at acid (stomach), but neutral or alkali soluble (enteron aisle).Capsulae enterosolubilis also can wrap up in enteric layer preparation by spray on non-capsulae enterosolubilis.The preparation method of capsulae enterosolubilis is within the scope of well-known to those skilled in the art.
In the present invention, the taxanes for the treatment of cancer of the stomach is administered orally anticarcinogen and also can be prepared into conventional (non-enteric) capsule, and the preparation method of capsule is within the scope of well-known to those skilled in the art.
Before hard shell capsules preparation, described active material, adjuvant, and pharmaceutical carrier can add appropriate other inert carriers such as starch etc. after thorough mix-ing, then it is prepared into dry powder with spray drying process or other seasonings, then by designed UD filling or be wrapped in hard shell capsules.Described active material, adjuvant, and pharmaceutical carrier also can be prepared into powdered reagent respectively, then filled with unit dosage forms in proportion or are wrapped in hard shell capsules.The described methods such as spray drying process prepare the preparation method of dry powder within the scope of well-known to those skilled in the art.
In the present invention, the taxanes for the treatment of cancer of the stomach is administered orally anticarcinogen and also can be prepared into conventional (non-enteric) tablet, and the preparation method of tablet is within the scope of well-known to those skilled in the art.
In the present invention, include chemotherapy kind anti-cancer drugs in tablet, wherein choice drug is taxane class of anti-cancer agents.In described Tabules, including taxane class of anti-cancer agents, Omega-3 aliphatic acid, dietary fiber, adjuvant (e.g., pharmaceutical carrier).Taxane class of anti-cancer agents includes taxol, Docetaxel or Cabazitaxel.In UD (with piece as measurement unit, that is, UD refers to a piece of taxanes tablet to UD), taxane class of anti-cancer agents content is about 10-200 milligram, about 20-150 milligram, about 40-100 milligram, preferably 40-80 milligram.Omega-3 content of fatty acid is about 100-800 milligram, about 200-600 milligram, about 300-500 milligram, preferably 300-400 milligram.Dietary fiber such as semen pulicariae shell content of powder is about 200-2000 milligram, about 400-1500 milligram, preferably 500-1000 milligram.Pharmaceutical carrier content is about 60-300 milligram, preferably 100-200 milligram.
Before tablet preparation, described active material taxol and Omega-3 aliphatic acid, adjuvant (pharmaceutical carrier) can add appropriate other inert carriers such as starch etc. after thorough mix-ing, then it is prepared into dry powder with spray drying process or other oven drying methods, add dietary fiber pulvis, then again the method that designed UD pressed disc method or other industry are commonly used is prepared piece agent.Described active material, adjuvant (pharmaceutical carrier) also can be prepared into powdered reagent respectively, then prepares piece agent with unit dosage forms in proportion.The described methods such as spray drying process prepare the preparation method of dry powder within the scope of well-known to those skilled in the art.
In the present invention, the taxanes for the treatment of intestinal cancer is administered orally anticarcinogen and can be prepared into enteric coatel tablets.The preparation method of enteric coatel tablets is to wrap up in enteric layer by spray on non-enteric coatel tablets, or is prepared with direct method.The preparation method of enteric coatel tablets is within the scope of well-known to those skilled in the art.
In the present invention, include chemotherapy kind anti-cancer drugs in enteric coatel tablets, wherein choice drug is taxane class of anti-cancer agents.In described enteric coatel tablets, including taxane class of anti-cancer agents, Omega-3 aliphatic acid, dietary fiber, adjuvant (e.g., pharmaceutical carrier).Taxane class of anti-cancer agents includes taxol, Docetaxel or Cabazitaxel.In UD (with piece as measurement unit, that is, UD refers to a piece of taxanes enteric coatel tablets to UD), taxane class of anti-cancer agents content is about 10-200 milligram, about 20-150 milligram, about 40-100 milligram, preferably 40-80 milligram.Omega-3 content of fatty acid is about 50-400 milligram, about 100-300 milli, preferably 150-200 milligram.Dietary fiber content is about 50-400 milligram, about 100-300 milligram, preferably 150-200 milligram；Pharmaceutical carrier content is about 60-300 milligram, preferably 100-200 milligram.
Pharmaceutical carrier can promote dissolving and the bioavailability of chemotherapeutic class active material.Pharmaceutical carrier can be D- α-cetomacrogol 1000 succinate (TPGS,D-alpha-tocopheryl polyethylene glycol 1000succinate)，And/or octanoic acid LABRAFIL M 1944CS，And/or capric acid LABRAFIL M 1944CS (Labrasol,caprylocaproyl macrogol-8glycerides)，And/or list oleic acid sorbitan ester (Sorbitan monooleate)，And/or ascorbyl palmitate (Ascorbyl palmitate)，And/or polyoxyethylene olein (LabraWl M 1944CS,polyoxyethylated oleic glycerides)，And/or polyethylene glycol，And/or the mixture of absolute ethyl alcohol.
The composition that this patent provides can be supplied to patient with the acceptable oral dosage form of any medicine.Preferably chemotherapy drug composition is to be prepared into pill, tablet, or the peroral dosage form of the form such as capsule.This patent also provides pharmaceutical composition, including the pharmaceutical dosage form of unit dosage form.In this kind of dosage form, formulation following can be divided into appropriately sized UD.This dosage contains the composition active component of the appropriate amount reaching therapeutic purpose enough.
The present invention provides capsule (soft capsule and hard shell capsules etc.), tablet, liquid, syrup state, suspension liquid, sublingual tablet, candy type accordingly, and chews the combination dosage form of sheet form.
The present invention also includes the preparation method of the pharmaceutical composition of institute's inventive composition formulation.
Pharmaceutical dosage form can include drug excipient.Excipient must be to be suitable for patient's application, and conventional is nontoxic, low toxicity and highly purified.
Drug excipient selects according to application form, such as oral tablet, capsule, powder-type, syrup type, floating type etc..Drug excipient should be consistent with traditional process for preparing medicine, and be the industry technical field known to.The oral capsule of such as institute's inventive composition formulation can include preservative, flavor enhancement, and colouring agent etc..
The present invention includes the solid dosage forms as tablet and capsule.The preparation method of capsule is by composition as above implant capsule shell when producing.Paclitaxel composition is to be filled in hard shell capsules or soft capsule in certain embodiments.Capsule shells can use methylcellulose, hydroxypropylmethyl cellulose, polyvinyl alcohols, or denatured gelatins gelatin or starch or other materials preparation.Hard-shell capsule is usually to be prepared with the bone of high glue intensity and the mixture of pigskin gelatin.Unit dosage form is a gel capsule in certain embodiments.Capsule shells are glycerine capsule shells in certain embodiments.Capsule shells are Bos taurus domesticus Gmelin shells in further embodiments.The raw material that other are suitable for doing capsule shells includes polyethylene, polypropylene, poly (methylmethacrylate), polyvinylchloride, polystyren e, polyurethanes, polytetrafluoroethylene, nylons, polyformaldehydes, polyesters, ellulose acetate, and nitrocellulose.Capsule shells itself can the pigment containing a small amount of, opacifying agent, plasticizer, and preservative.Prepare other Solid Dosage Forms conventional method such as prepare suppository etc. also it is known that.Gelatine capsule shell can also use Tapioca starch, grass, prepared by vegetables source and fish source gelatin.
In other examples, capsule shells comprise speed limit membrane material, including coating, the inside filling present composition active component.Capsule shells can use porous or pH-sensitive condensate, with the method preparation of heat forming technology.Capsule shells are anisotropic membranes in certain embodiments, are the film that there is thin skin on a surface, but the thickness of most of film is to be made up of highly permeable material.The active component of described composition is in the soft capsule be filled in enteric coating preparation in certain embodiments.Capsulae enterosolubilis can with those skilled in the art all known to standard method preparation.
The active component of institute's inventive composition is to be filled in slow release or/and the capsule of long-term release, to ensure the release of in good time He stable active component in certain embodiments.In those skilled in the art, the technology of preparing of various different sustained releases or/and sustained release formulation type is well-known.
As one useful illustration of capsulae enterosolubilis, a kind of " expansion plug device " can be employed.The active component of described composition can be filled in the capsule of soluble half, and second half of then capsule is sealed with water-setting plug.This water-setting plug expands in aqueous environment, then after expanding into a time for design in advance, deviates from from capsule.Result is that the capsule of the half containing active component is opened, and active component both can spread in the environment of the aqueous solution.Preferably hydrogel plug capsule is that does not have active material to discharge before leaving stomach substantially, 15 minutes or longer just discharge after entering enteron aisle.Preferably 30 minutes or longer, so may insure that minimal combination active substances discharge in stomach, locally discharge in the large intestine or rectum in pathogenesis of cancer area to greatest extent.
Conventional method for preparing tablet thereof is well-known in the art.The method includes spray drying process, directly compression and compressing grains, or wet method or other special methods.
Liquid dosage form includes being prepared into solution, suspension and emulsion.The illustration of liquid drug formulation includes propyleneglycoles solution and is prepared into the oral liquid containing sweetener, suspension and emulsion.
Described composition can comprise a kind of plasticizer, particularly in capsule shells.Suitable plasticizer includes such as macrogol (PEG) class, such as PEG 300, PEG 400, PEG 600, PEG 1450, PEG 3350, and PEG 800, stearic acid, macrogol, oleic acid, triethyl group cellulose, and glyceryl triacetate.
Described combination dosage form can be with coating.Described coating can use enteric coating, and that is, coating used mainly dissolves in enteral, but substantially soluble in gastric juice.The illustration of enteric coating includes polyvinyl acetate phthalate (PVAP).In addition, what follows enteric condensate can be applied：Colorcon.RTM.,hydroxypropylmethylcellulose acetate succinate(HPMCAS),cellulose acetate phthalate(CAP),methacrylic acid copolymer,hydroxypropylmethylcellulose succinate,cellulose acetate succinate,cellulose acetate hexahydrophthalate,hydroxypropylmethylcellulose hexahydrophthalate,hydroxypropylmethylcellulose phthalate(HPMCP),cellulose propionate phthalate,cellulose acetate maleate,cellulose acetate trimellitate,cellulose acetate butyrate,cellulose acetate propionate,methacrylic acid/methacrylate polymer,methacrylic acid-methyl methacrylate copolymer,ethyl methacrylate-methylmethacrylate-chlorotrimethylammonium ethyl methacrylate copolymer，With similar，The polymeric combination with one or more enteric as described above.Other illustrations include nature resin, such as shellac, SANDARAC, copal collophorium, and as above polymeric combination described in one or more.The polymeric illustration of other enterics includes hydroxyl synthetic resin further.
Described composition can include a kind of stabilizer." stabilizer " includes to keep the compound of desired formulation attribute in certain time, this attribute including but not limited to can in laboratory inspection to mechanical, chemistry, and the resistance of the infringement of temperature.This attribute includes the effect to concentration, being marked, and keeps the purity specified, and in GI dispersed and the no homogenizing of obvious degradation static stabilization in the presence of stabilizer.Described stabilizer is antioxidant in certain embodiments, such as vitamin E.Other suitable antioxidants include phenmethylol, butyrate, benzoquinones, and ascorbic acid (vitamin C).
Described composition can include a kind of preservative.Preservative is the compound suppressing growth of microorganism, and is normally incorporated in pharmaceutical dosage form and prevents growth of microorganism.The amount of typical preservative according to USP and EU method test and can determine.Preservative includes but is not limited to sorbic acid first, methyl p-hydroxybenzoate, propylparaben, benzoic acid and its salt, other p-hydroxybenzoic acid fat such as butyl p-hydroxybenzoates, alcohol type such as ethanol and benzene alcohol, phenol compound such as phenol, or level Four compound such as benzalkonium chloride.
Colouring agent provides composition or formulation color.This kind of excipient can include food grade pigment and food grade pigment absorbs on a kind of suitable adsorbent such as clay or aluminum oxide.The consumption of colouring agent can be adjusted, the composition of weight or from about 0.1% to about 1% such as from about 0.1% to about 5%.
The present invention provides and includes applying described composition as the method for the treatment of alimentary tract cancer.
The present invention provides the patient to needing for institute's inventive composition, carries out treating gi system cancer.Non-human patients include domestic animal, such as ox, sheep, and horse and house pet, such as cat and dog.
It will be appreciated that the dosage level needed for a patient is different.Special dosage is different according to different situations, including the activity of compound used therefor, the age of patient, body weight, health status, sex, administration time, route of administration, excludes speed, combination with medication, and order of severity of treated disease etc..
In one embodiment, a composition described herein can be administered for once or twice daily or three times.In another embodiment, 1,2,3,4,5,6,7,8 capsules of patient, the active component of the combination dosage form containing the specific combination of the present invention for each capsule can be given daily.In another embodiment, patient 1 or 2 or multiple capsules can be given every morning, such as from about early 5 points are arrived at about early 11 points, then patient 1 or 2 or multiple capsules can be given every night again, such as from about late 5 points Dao about late 11 points, each capsule contains the active component of the Omega-3 combination dosage form of specific combination described herein.
In another embodiment, 1,2,3,4,5,6,7,8 capsules of patient can be given daily, each capsule single-activity component in the combination dosage form containing the specific combination of the present invention respectively.In another embodiment, described single-activity Ingredients Capsule can be taken simultaneously or asynchronously.In another embodiment, patient 1 or 2 or multiple described single capsule can be given every morning, such as from about early 5 points are arrived at about early 11 points, then patient 1 or 2 or multiple capsules can be given every night again, such as from about late 5 points Dao about late 11 points, these Capsules group collectively form the required all active components strengthening formulation of patient.
In another embodiment, the available composition of method is oral administered dosage form accordingly.Noun " oral administration " or " peroral dosage form " here include a kind of form of medication to any type of drug ingedient or composition, specially put into drug ingedient or composition after in the oral cavity of patient or swallow or do not swallow.So " oral administration " includes oral cavity and sublingual and esophagus form of medication.In one embodiment, this composition is in a capsule, for example gel soft capsule.
The composition of the present invention can be pressed one or more unit dosage unit formula.Noun " UD " herein or " unit dosage forms " refer to a part for medical composition, and this composition contains a certain amount of medicable invented formulation being applied to single administration.This UD can with (i.e. 1 to about 10,1 to about 8,1 to about 6,1 to about 4,1 to about 2) one or more times daily, or any cause medicine reaction and medicable number of times administration.
The local of the treatment cancer of the stomach of the present invention is administered mechanism：After taking, chemotherapy class active material such as taxol dissolves and inhibition cancer cell division in stomach, but does not affect normal cell, thus reaching the selective effect killing tumour cell.Omega-3 active material immunity-regulating system simultaneously, offsets the side effect of chemotherapy class active material, and increases the therapeutic effect of chemotherapy class active material.Dietary fiber also can reduce has a stomach upset, and reduces system and absorbs.In the such as taxanes active material release of chemotherapy class, because the enteron aisle exclusion caused by P-gp, and the liver degraded that CYP3A4 causes, only and a small amount of taxane can enter system, greatly reduce toxic and side effect.
The local of the treatment intestinal cancer of the present invention is administered mechanism：After taking, enteric formulation is insoluble in stomach, and in enteral dissolving and inhibition cancer cell divides chemotherapy class active material such as taxol, but does not affect normal cell, thus reaching selective killing colon cancer or the effect of carcinoma of the rectum tumour cell.Omega-3 active material immunity-regulating system simultaneously, offsets the side effect of chemotherapy class active material, and increases the therapeutic effect of chemotherapy class active material.Dietary fiber can also increase therapeutic effect, reduce system and absorb.In the such as taxanes active material release of chemotherapy class medicine, because the enteron aisle exclusion caused by P-gp, and the liver degraded that CYP3A4 causes, only and a small amount of taxane can enter system, greatly reduce toxic and side effect.
The local of the treatment carcinoma of mouth of the present invention and laryngocarcinoma is administered mechanism：With sublingual or lozenge agent for slow releasing type, in lesions position dissolving and inhibition cancer cell divides chemotherapy class active material such as taxol, but does not affect normal cell, thus reaching the selective effect killing tumour cell.Omega-3 active material immunity-regulating system simultaneously, offsets the side effect of chemotherapy class active material, and increases the therapeutic effect of chemotherapy class active material.Dietary fiber also can reduce poison and pay effect, reduce system and absorb.
The invention has the beneficial effects as follows：
1. stomach is molten, capsulae enterosolubilis or sublingual and be directed to different diseases, local or target administration containing tablet, significantly increases curative effect, reduces toxic and side effect.
2. the present invention solves the problems, such as toxicity and the curative effect of system administration such as injection.In addition, because peroral dosage form is easier, being more easy to adjust taking dose and time, easily regulating and controlling the treatment concentration of chemotherapeutic class such as Japanese yew class active material, the concentration of controllable taxone maintains effectively treatment concentration during treating and is less than toxic concentration.Compared with the taxone formulation of prior art injection formulation, continuous therapeutic purposes can be reached with long-term taking, without " shock therapy " treated again after the muscle power to be restored that will be discontinued after treating one section.
Brief description
Fig. 1 is to do taxol composite dosage form experimental result picture with mouse junction cancer model.
Specific embodiment
Following illustration illustrates that the present invention, is not to limit invention.
Embodiment 1 treats the taxanes soft capsule oral preparation medicament of cancer of the stomach
Preparation method is as follows：
1. 3.0 kilograms of taxols are dissolved in 17 kilograms of Omega-3 aliphatic acid, (weight compares 1 to the mixture of 4 kilograms of D- α-cetomacrogol 1000 succinates (TPGS, D-alpha-tocopheryl polyethylene glycol 1000succinate), 2.8 kilograms of sad LABRAFIL M 1944CSs and capric acid LABRAFIL M 1944CS：1), in 1 kilogram of single oleic acid sorbitan ester (Sorbitan monooleate), 0.2 kilogram of ascorbyl palmitate (Ascorbyl palmitate) and 2 kilograms of absolute ethyl alcohols.This formula is fully mixed.This amount filled a prescription as 100,000 UDs.
Taxol can also replace with Docetaxel or Cabazitaxel.
Omega-3 aliphatic acid can also adopt ethyl ester, or triglyceride, or free acid form, weight ratio, EPA/DHA=3/2).
2. by step 1) mixture soft capsule packing machine, above-mentioned composition is wrapped in flexible glue is intracapsular, the taxane anticarcinogen soft capsule of the treatment cancer of the stomach of 100,000 UD is obtained.In every soft capsule, contain：30mg taxol, 170mgOmega-3 aliphatic acid, 100mg adjuvant.
3. 60.0 kilograms of semen pulicariae shell powder hard shell capsules filling machines are filled in that 100,000 ebonite is intracapsular, prepare the semen pulicariae shell capsule preparations that every capsule contains 600mg.
4. patient according to doctor's advice, each takes taxane anticarcinogen soft capsule and semen pulicariae capsule each 1-4 grain, when taking paclitaxel capsule and semen pulicariae shell capsule to take number equal, daily 2-10 time.
Embodiment 2 treats the taxanes enteric soft capsules oral preparation medicament of intestinal cancer
Preparation method is as follows：
1. 3.0 kilograms of taxols are dissolved in 17 kilograms of Omega-3 aliphatic acid, 4 kilograms of D- α-cetomacrogol 1000 succinates, (weight compares 1 to the mixture of 2.8 kilograms of sad LABRAFIL M 1944CSs and capric acid LABRAFIL M 1944CS：1), in 1 kilogram of single oleic acid sorbitan ester, 0.2 kilogram of ascorbyl palmitate and 2 kilograms of absolute ethyl alcohols.This formula is fully mixed, this fills a prescription as 100, the amount of 000 UD.
2. use soft capsule packing machine, the above-mentioned composition of UD is wrapped in flexible glue intracapsular；Then wrap up in capsulae enterosolubilis layer in outer capsule layer spray again, that is, the taxane anticarcinogen soft capsule of the treatment intestinal cancer of 100,000 UD is obtained.Every soft capsule contains：30mg taxol, 170mg Omega-3 aliphatic acid, 100mg adjuvant.
3. 60.0 kilograms of semen pulicariae shell powder hard shell capsules filling machines are filled in that 100,000 ebonite is intracapsular, prepare the semen pulicariae capsule preparations that each capsule contains 600 milligrams.
4. patient according to doctor's advice, each takes taxane anticarcinogen soft capsule and semen pulicariae capsule each 1-4 grain, when taking paclitaxel capsule and semen pulicariae shell capsule to take number equal, daily 2-10 time.
Embodiment 3 treats the taxanes hard shell capsules oral preparation medicament of cancer of the stomach
Preparation method is as follows：
1. 3.0 kilograms of taxols are dissolved in 17 kilograms of Omega-3 aliphatic acid, 4 kilograms of D- α-cetomacrogol 1000 succinates, (weight compares 1 to the mixture of 2.8 kilograms of sad LABRAFIL M 1944CSs and capric acid LABRAFIL M 1944CS：1), in 1 kilogram of single oleic acid sorbitan ester, 0.2 kilogram of ascorbyl palmitate and 2 kilograms of absolute ethyl alcohols.This formula is fully mixed, then plus about the water of equivalent and emulsifying agent and appropriate carrier, move into homogenizer and fully mix, then move into spray dryer and be prepared into uniform powder.Prepared powder is sufficiently mixed with 60.0 kilograms of semen pulicariae shell powder again.This amount filled a prescription as 200,000 UDs.
2. use hard capsule filler, the above-mentioned composition of UD is filled in ebonite is intracapsular, the taxane anticarcinogen hard shell capsules of the treatment intestinal cancer of 200,000 UD are both obtained.Every soft capsule contains：15mg taxol, 85mg Omega-3 aliphatic acid, 50mg adjuvant, and 300 milligrams of semen pulicariae shells.
3. patient, according to doctor's advice, each takes 2-8 grain, daily 2-10 time.
Embodiment 4 treats the taxanes hard shell capsules oral preparation medicament of intestinal cancer
Preparation method is as follows：
1. 3.0 kilograms of taxols are dissolved in 17 kilograms of Omega-3 aliphatic acid, 4 kilograms of D- α-cetomacrogol 1000 succinates, in the mixture of 2.8 kilograms of sad LABRAFIL M 1944CSs and capric acid LABRAFIL M 1944CS, 1 kilogram of single oleic acid sorbitan ester, 0.2 kilogram of ascorbyl palmitate and 2 kilograms of absolute ethyl alcohols.The fully dissolving of this formula is mixed, then plus about the water of equivalent and emulsifying agent and appropriate carrier, move into homogenizer and fully mix, then move into spray dryer and be prepared into uniform powder.Prepared powder is sufficiently mixed with 60.0 kilograms of semen pulicariae shell powder again.This amount filled a prescription as 200,000 UDs.
2. use hard capsule filler, the above-mentioned composition of UD is filled in ebonite intracapsular；Then wrap up in capsulae enterosolubilis layer in outer capsule layer spray again, that is, the taxane anticarcinogen hard shell capsules of the treatment intestinal cancer of 200,000 UD are obtained.Every soft capsule contains：15mg taxol, 85mg Omega-3 aliphatic acid, 50mg adjuvant, and 300 milligrams of semen pulicariae shells.
3. patient, according to doctor's advice, each takes 2-8 grain, daily 2-10 time.
Embodiment 5 treats the taxanes tablet oral preparation medicament of cancer of the stomach
Preparation method is as follows：
1. 3.0 kilograms of taxols are dissolved in：17 kilograms of Omega-3 aliphatic acid, 4 kilograms of D- α-cetomacrogol 1000 succinates, in the mixture of 2.8 kilograms of sad LABRAFIL M 1944CSs and capric acid LABRAFIL M 1944CS, 1 kilogram of single oleic acid sorbitan ester, 0.2 kilogram of ascorbyl palmitate and 2 kilograms of absolute ethyl alcohols.The fully dissolving of this formula is mixed, then plus the about water of equivalent and emulsifying agent, and other additives such as starch etc., move into homogenizer and fully mix, then (a) moves into spray dryer and is prepared into uniform powder, or (b) is prepared into dry powder with oven drying method.Prepared powder is sufficiently mixed with 60.0 kilograms of semen pulicariae shell powder again.This amount filled a prescription as 200,000 UDs.
2. by powder press UD above-mentioned composition tabletted with tablet press machine, that is, be obtained 200,000 UD treatment intestinal cancer taxane anticancer tablet.Every contains：15mg taxol, 85mg Omega-3 aliphatic acid, 50mg adjuvant, and 300 milligrams of semen pulicariae shells.
3. patient, according to doctor's advice, each takes 2-8 grain, daily 2-10 time.
Embodiment 6 treats the taxanes tablet oral preparation medicament of intestinal cancer
Preparation method is as follows：
1. 3.0 kilograms of taxols are dissolved in：17 kilograms of Omega-3 aliphatic acid, 4 kilograms of D- α-cetomacrogol 1000 succinates, the mixture of 2.8 kilograms of sad LABRAFIL M 1944CSs and capric acid LABRAFIL M 1944CS, 1 kilogram of single oleic acid sorbitan ester, 0.2 kilogram of ascorbyl palmitate and 2 kilograms of absolute ethyl alcohols.The fully dissolving of this formula is mixed, then plus about the water of equivalent and emulsifying agent, move into homogenizer and fully mix, then (a) moves into spray dryer and be prepared into uniform powder, or (b) is prepared into dry powder with oven drying method.Prepared powder is sufficiently mixed with 60.0 kilograms of semen pulicariae shell powder again.This amount filled a prescription as 200,000 UDs.
2. by powder press UD above-mentioned composition tabletted with tablet press machine, then again tablet outer layer spray wrap up in enteric integument, that is, be obtained 200,000 UD treatment intestinal cancer taxane anticancer tablet.Every contains：15mg taxol, 85mg Omega-3 aliphatic acid, 50mg adjuvant, and 300 milligrams of semen pulicariae shells.
3. patient, according to doctor's advice, each takes 2-8 grain, daily 2-10 time.
Embodiment 7
Zoopery：The experiment of taxol composite dosage form is done with mouse junction cancer model.As shown in figure 1, mouse Colon knurl grew to about 50mm when 15 days3, enter fast growing period within 18 days.This experimental drug initiateed the phase for the 15th day.If being explicitly shown alone taxol medicine by Fig. 1, tumour grows from 20 days start indexs.Plus the speed of growth slows down after dietary fiber, Omega-3 is added to slow down substantially, but the composite dosage form invented with this patent, including taxol, Omega-3, and dietary fiber, tumour growth is substantially controlled, that is, reached therapeutic effect.This experiment has clearly showed the incomparable therapeutic effect of this composite dosage form.
Mouse Colon carcinoma animal model explanation：By 60 milligrams of the taxol each dosage of adult, then mouse is 0.16 milli gram/times.Following microcapsule formulation is according to this metering design.Medicinal application send food method in mouse using gavage, and each experimental point is 1 statistics of 5 experimental datas.Designed capsule metering is as follows：
Taxol microcapsule formulation：Capsulae enterosolubilis contains 0.16 milligram of taxol, 1.00 milligrams of adjuvants.
Taxol+dietary fiber microcapsule formulation：Capsulae enterosolubilis contains 0.16 milligram of taxol, 1.00 milligrams of adjuvants, 3.12 milligrams of dietary fibers.
Taxol+Omega-3 microcapsule formulation：Capsulae enterosolubilis contains 0.16 milligram of taxol, 0.88 milligram of Omega-3,1.00 milligrams of adjuvants, 3.12 milligrams of dietary fibers.
Taxol+Omega-3+ dietary fiber microcapsule formulation:Capsulae enterosolubilis contains 0.16 milligram of taxol, 0.88 milligram of Omega-3,1.00 milligrams of adjuvants, 3.12 milligrams of dietary fibers.
In design, adjuvant is in proportion, 4 kilograms of D- α-cetomacrogol 1000 succinates, the mixture of 2.8 kilograms of sad LABRAFIL M 1944CSs and capric acid LABRAFIL M 1944CS, the mixture of 1 kilogram of single oleic acid sorbitan ester, 0.2 kilogram of ascorbyl palmitate and 2 kilograms of absolute ethyl alcohols.
Dietary fiber is semen pulicariae shell.
Claims (10)
1. a kind of chemotherapy kind anti-cancer drugs oral preparation composition it is characterised in that：Active ingredient includes chemotherapy kind anti-cancer drugs, Omega-
3 aliphatic acid, dietary fiber and adjuvant.
2. chemotherapy kind anti-cancer drugs oral preparation composition as claimed in claim 1 it is characterised in that：Described chemotherapy kind anti-cancer drugs
Including alkylating agents anticarcinogen, anti-metabolism anticarcinogen and antitumor animals and plants composition kind anti-cancer drugs.
3. chemotherapy kind anti-cancer drugs oral preparation composition as claimed in claim 2 it is characterised in that：Described antitumor animals and plants
Composition kind anti-cancer drugs include taxane class of anti-cancer agents；In UD, taxane class of anti-cancer agents content is 10～200 millis
Gram.
4. chemotherapy kind anti-cancer drugs oral preparation composition as claimed in claim 3 it is characterised in that：Described taxanes anticancer
Medicine includes taxol, Docetaxel and Cabazitaxel.
5. chemotherapy kind anti-cancer drugs oral preparation composition as claimed in claim 1 it is characterised in that：Described Omega-3 fat
Acid comprises EPA and/or DHA；In UD, Omega-3 content of fatty acid is 100～800 milligrams.
6. chemotherapy kind anti-cancer drugs oral preparation composition as claimed in claim 5 it is characterised in that：When Omega-3 aliphatic acid bag
During containing EPA and DHA, by weight, EPA:DHA is 10:90～90:10.
7. chemotherapy kind anti-cancer drugs oral preparation composition as claimed in claim 1 it is characterised in that：Described dietary fiber includes
Foodstuff dietary fiber and health care productses dietary fiber；In unit dosage, the content of dietary fiber is 200～2000 millis
Gram.
8. chemotherapy kind anti-cancer drugs oral preparation composition as claimed in claim 7 it is characterised in that：Described dietary fiber includes
Semen pulicariae shell.
9. chemotherapy kind anti-cancer drugs oral preparation composition as claimed in claim 1 it is characterised in that：Described adjuvant includes medicine
Thing carrier；Described pharmaceutical carrier includes D- α-cetomacrogol 1000 succinate, and/or sad polyethylene glycol glycerol
Ester, and/or capric acid LABRAFIL M 1944CS, and/or single oleic acid sorbitan ester, and/or vitamin-c palmitate
Ester, and/or polyoxyethylene olein, and/or polyethylene glycol, and/or absolute ethyl alcohol；In unit dosage, auxiliary
Agent content is 60～300 milligrams.
10. chemotherapy kind anti-cancer drugs oral preparation composition as claimed in claim 1 it is characterised in that：It is by described in claim 1
Composition be prepared into peroral dosage form in capsule shells, or by one of composition described in claim 1 or two
Plant active ingredient to be prepared in different capsule shells, the peroral dosage form simultaneously or asynchronously taken.
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| CN201510465527.6A CN106390122A (en) | 2015-07-31 | 2015-07-31 | Oral composition of anticancer chemotherapeutic preparations |
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| CN201510465527.6A CN106390122A (en) | 2015-07-31 | 2015-07-31 | Oral composition of anticancer chemotherapeutic preparations |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110327430A (en) * | 2019-07-26 | 2019-10-15 | 李庆华 | A kind of anticancer therapy medicament |
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| CN103200939A (en) * | 2010-09-03 | 2013-07-10 | 弗雷泽纽斯卡比德国有限公司 | Composition comprising a combination of DHA and EPA for administration prior to commencement of chemotherapy |
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