CN101380461A - Efficient thymosin enteric-coated tablets and thymosin for injection - Google Patents
Efficient thymosin enteric-coated tablets and thymosin for injection Download PDFInfo
- Publication number
- CN101380461A CN101380461A CNA2008101669277A CN200810166927A CN101380461A CN 101380461 A CN101380461 A CN 101380461A CN A2008101669277 A CNA2008101669277 A CN A2008101669277A CN 200810166927 A CN200810166927 A CN 200810166927A CN 101380461 A CN101380461 A CN 101380461A
- Authority
- CN
- China
- Prior art keywords
- thymosin
- preparation
- biotin
- poloxamer
- enteric
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- LCJVIYPJPCBWKS-NXPQJCNCSA-N thymosin Chemical compound SC[C@@H](N)C(=O)N[C@H](CO)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CO)C(=O)N[C@H](CO)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@H]([C@H](C)O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@H](CCC(O)=O)C(O)=O LCJVIYPJPCBWKS-NXPQJCNCSA-N 0.000 title claims abstract description 113
- 102000007501 Thymosin Human genes 0.000 title claims abstract description 111
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- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims abstract description 94
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Abstract
The invention relates to a drug composite of thymosin and biotin and a preparation thereof, such as a thymosin enteric-coated tablet and a thymosin preparation used for injection, in particular to the thymosin enteric-coated tablet, which comprises thymosin, tween 80 and poloxamer, wherein, the weight ratio of the tween 80 and the poloxamer is 1: 1-20, and 1:8 is preferable; and the weight ratio of poloxamer and the thymosin is 0.2-20:1. In addition, the invention also relates to the application of the drug composite or the preparation, such as the application to the treatment of chronic hepatitis, viral hepatitis and cirrhosis, a variety of primary or secondary T lymphocyte deficiency, autoimmune diseases, low cell immune function related diseases and to the adjuvant treatment of neoplastic disorder or to the preparation of corresponding drugs. Especially, the thymosin enteric-coated tablet can be promptly released in the enteron so as to enhance the drug absorption rate and greatly increase the bioavailability of the drug.
Description
Technical field
The invention belongs to medical technical field, particularly, it relates to the pharmaceutical composition and the preparation thereof of thymosin and biotin, especially thymosin enteric coatel tablets and injection Thymopeptide.In addition, the invention still further relates to the application of aforementioned pharmaceutical compositions or preparation, as be used to prevent and/or treat chronic hepatitis, viral hepatitis and liver cirrhosis, various constitutional or Secondary cases T lymphocyte defective disease, autoimmune disease, the purposes of disease that cellular immune function is lowly relevant etc. or preparation relative medicine.
Background technology
Thymus is the important immune organ of human body, and it can secrete multiple important hormone, as thymopoietins, thymosin etc.Wherein, (have another name called thymosin, thymosin) be the excretory one group of polypeptide with physiologically active of thymic tissue to thymosin, and it is to extract from the thymus the inside of calf, pig to obtain a class polypeptide hormone at first, and molecular weight is below 5000.Can obtain at present by chemosynthesis and genetic engineering means.
Thymosin has adjusting and strengthens the effect of human body cell immunologic function, can impel the T lymphocyte maturation in the peripheral blood after mitogen activates, increase the T cell in various antigens or the former secretion that activates the various lymphokines in back (as: α, IFN-, interleukin-22 and interleukin-13) of mitogenesis, increase the level of lymphokine receptor on the T cell.It strengthens lymphocytic effect by the activation to the T4 accessory cell simultaneously.Therefore, thymosin can be widely used in clinical treatment at present, as prevents and/or treats infectious disease such as hepatitis B, hepatitis C; Malignant tumor such as nonsmall-cell lung cancer, malignant melanoma, hepatocarcinoma, gastric cancer; Autoimmune disease as myasthenia gravis, systemic lupus erythematosus (sle), rheumatoid arthritis etc., also is used for the treatment of dermatosis, anaphylactoid purpura, pulmonary tuberculosis, upper respiratory tract infection.
Thymosin also makes up with other drug and treats disease.For example, the Chinese patent application compositions that discloses thymosin and lamivudine for No. 99811382 is used for the treatment of hepatitis B infection; Chinese patent application discloses use thymosin, interferon and ribavirin therapy hepatitis C No. 01813766; Chinese patent application discloses the use thymosin No. 01815969 and glycol interferon moral compositions is treated hepatitis C.But, thereby not studies show that thymosin and biotin can make up the report that raising immunity prevents and/or treats relevant disease at present.
Comprise carboxylic side-chain and two five-ring heterocycles that contain 5 carbon atoms in the chemical constitution of biotin (Biotin), carboxyl by side chain combines with the ε-lysine residue of pheron in vivo, the effect of performance coenzyme in lipid, sugar, aminoacid and energy metabolism.Biotin can adopt chemosynthesis preparation, but at present adopts microbial fermentation technology to prepare more, as can be referring to No. the 85103248th, 93102377,94107234,97111201, Chinese patent application etc.
Current, biotin is except the supplement as vitamin, and it is mainly used is that the molecule that serves as a mark has come the effect of labelling, thus be applied to research, detect and diagnosis in.For example, there is the report biotin can labelling thymosin or its analog, is used for scientific research, as referring to Biol Chem.2001Oct; 382 (10): 1473-82 etc.In addition, U.S. Patent application US2007243132A discloses a kind of water-in-oil microemulsion agent, wherein effective ingredient can be selected from the huge group that comprises thymosin and biotin, be the relation of selecting between each composition, also clearly do not point out thymosin and biotin can make up raising immunity and co-production becomes combination preparation more efficiently.
The inventor is through painstaking efforts, the combination of having found thymosin and biotin surprisingly has synergism, can significantly improve immunity, thereby can prevent and/or treat corresponding disease more efficiently, and/or be prepared into pharmaceutical composition and the preparation that prevents or treat corresponding disease.Therefore, the inventor has proposed a kind of pharmaceutical composition efficiently and preparation that comprises thymosin and biotin, and especially preferably enteric coated tablet and injection are used for efficient human body immunity improving power, thereby prevent and/or treat corresponding disease better.In addition, because thymosin is polypeptides matter, molecular weight is bigger, and is fat-soluble poor, is not easy to see through biomembrane, easily become aminoacid, little peptide by the enzymatic degradation in the gastrointestinal tract when especially thymosin is oral and loses activity.Therefore the inventor has optimized a kind of enteric coatel tablets prescription especially through painstaking efforts, not only by oral convenient drug administration patient's long-term prescription, and has improved its bioavailability greatly, makes medicine more efficient.
Summary of the invention
Lack in prior art under the situation of thymosin medicine efficiently, the objective of the invention is to provides pharmaceutical composition efficiently in order to overcome the deficiencies in the prior art, and it comprises thymosin and biotin.Said composition not only can keep the pharmacological action of thymosin, and the interpolation of biotin can be worked in coordination with the performance that promotes drug effect.In addition, the present invention also provides the preparation and the application of this pharmaceutical composition, is specifically related to be used to prevent and/or treat the application of aspects such as lowly relevant disease of chronic hepatitis, viral hepatitis and liver cirrhosis, various constitutional or Secondary cases T lymphocyte defective disease, autoimmune disease, cellular immune function and neoplastic disease.In addition, the present invention also provides a kind of enteric coatel tablets prescription especially.
Particularly, in first aspect, the invention provides a kind of pharmaceutical composition, it comprises thymosin and biotin.This pharmaceutical composition can be brought into play the synergism of thymosin and biotin, significantly improves immunity, thereby can prevent and/or treat corresponding disease more efficiently.The inventor is through technical study experiment and pharmacodynamics test are found thymosin and biotin are made up with proper proportion many times, only there is the unit of thymosin medicine evident in efficacy being higher than, have obvious synergistic effect, improved the bioavailability of thymosin greatly.Preferred pharmaceutical composition of the present invention is made up of thymosin and biotin substantially, promptly is used for the active component of human body immunity improving power in this pharmaceutical composition by thymosin and biotin; Pharmaceutical composition most preferably of the present invention is made up of thymosin and biotin.In the present invention, " pharmaceutical composition " by those skilled in the art routine understand, be the product that is used to prevent and/or treat disease that mixes of composition wherein.Therefore, pharmaceutical composition of the present invention is not to be used to the biotin that detects, diagnose and the covalently bound conjugate of other polypeptides matters chemistry.
Thymosin is well-known to those skilled in the art, and it can be the natural thymosin that is extracted by animal, and it normally extracts from the thymus of animal (as mammals such as pig, cattle, sheep); It also can be thymosin or derivatives thereof by chemosynthesis, carry out as peptide synthetic technology by routine, correlative detail can be with reference to " Solid Phase Peptide Synthesis " (second edition) (Pierce Chemical Co., Rockford, Illinois (1984)); It also can be the thymosin or derivatives thereof of genetic engineering preparation, as constructing the expression vector that contains corresponding nucleic, it is imported in the host cell and under appropriate condition express by " molecular cloning experiment guide " described flow processs of handbook such as (Science Press (2002)) and instrument (as enzyme, experimental facilities etc.).The concrete example of thymosin is a lot, and is described as documents such as Chinese patents 200410087075,02805917,99805957,93120725,93119346.Therefore, " thymosin " used herein comprise by animal extract, chemosynthesis or the genetic engineering preparation, preferably extrasin alpha is more preferably thymosin.In addition, " thymosin " used herein also comprises the pharmaceutically acceptable salt of thymosin, example hydrochloric acid, phosphoric acid, sulphuric acid, acetic acid, succinic acid, maleic acid, citrate or hydroxide, ammonium, carbonate etc.Used " biotin " of the present invention is compound known, can prepare by microbial fermentation or chemosynthesis, but do not comprise that biotin and other polypeptides matters put together the complex of formation, this class complex is used for the immunology detection field usually, has obviously deviated from aim of the present invention.
In the pharmaceutical composition of first aspect present invention, the weight ratio of preferred wherein thymosin and biotin is 1-50:0.01-2.0,2-30:0.05-1.0 more preferably, 10-25:0.1-0.8 more preferably, in the specific embodiment of the present invention, the weight ratio of thymosin and biotin is 20:0.5.
In second aspect, the invention provides a kind of pharmaceutical preparation, it comprises described pharmaceutical composition of first aspect present invention and pharmaceutically acceptable adjuvant.Pharmaceutically acceptable adjuvant comprises pharmaceutically acceptable various adjuvant, carrier, and excipient, diluent, filler, absorption enhancer, enzyme inhibitor, disintegrating agent, lubricant, wetting agent and/or binding agent etc. are arranged, and they are compatible with active component.By pharmacy textbook or test handbook, use the conventional pharmaceutical preparation of pharmaceutically acceptable adjuvant preparation to know for those of ordinary skills.Pharmaceutical preparation of the present invention comprises the described pharmaceutical composition of first aspect present invention as active component, and this pharmaceutical composition and pharmaceutically acceptable adjuvant are combined, and is mixed with various preparations, is preferably solid preparation and liquid preparation.Preparation of the present invention can be unit dosage form, as tablet, pill, capsule (comprise continue to discharge or postpone to release releasing pattern), powder, suspensoid, granule, tincture, syrup, emulsion agent, suspension, injection, injectable powder (comprising lyophilized injectable powder), etc. dosage form and various slow release formulation, thereby be fit to various form of medication, for example oral, non-intestinal injection, mucosa, muscle, intravenous, subcutaneous, ophthalmic, Intradermal or through the form of medication of skin etc.The present invention is tablet, capsule, injection or injection lyophilized powder preferably.For example, can select for use normal saline and pharmaceutical composition of the present invention to be mixed with injection.
Because easily by enzymatic degradation, and biotin also just absorbs at the small intestinal place thymosin in gastrointestinal tract, so the especially preferred oral drug preparation of the present invention is the oral enteric preparation, preferably enteric coated capsule or enteric coatel tablets are more preferably enteric coatel tablets.Wherein, contain 1-50mg thymosin and 0.01-2.0mg biotin in preferred every tablet of enteric coatel tablets, more preferably contain 2-30mg thymosin and 0.05-1.0mg biotin, more preferably contain 10-25mg thymosin and 0.1-0.8mg biotin, in the specific embodiment of the present invention, every contains 20mg thymosin and 0.5mg biotin.Enteric coatel tablets of the present invention contain pharmaceutic adjuvant and enteric-coating material, for example pharmaceutic adjuvant can be selected from can be compatible with active component pharmaceutically acceptable filler, absorption enhancer, enzyme inhibitor, disintegrating agent, lubricant, wetting agent or binding agent in one or more.These adjuvants or material itself can be conventional and be recorded in textbook or the test handbook, and for example absorption enhancer is selected from one or more of fatty acid, cholic acid and salt thereof, oligochitosan, carbomer, poloxamer, tween 80, sodium lauryl sulphate.But the inventor has therefrom optimized prescription by the experiment of huge amount, makes its effect be better than existing enteric coatel tablets.The preferred absorption enhancer of the present invention is the combination of tween 80 and poloxamer.Particularly, the present invention provides a kind of thymosin enteric coatel tablets especially, it contains thymosin, Tween 80 and poloxamer, wherein the weight ratio of Tween 80 and poloxamer is 1:1-20 (being preferably 1:8), and wherein the weight ratio of poloxamer and thymosin is 0.2-20:1 (being preferably 10:1), and most preferably the weight ratio of thymosin, Tween 80 and poloxamer is 10:1:8.Such prescription can close the cell bypass approach by striding cell people having a common goal, also can because of the close-connected integrity of cell change and (or) inefficacy that effluxes systemic-function increases the permeability of medicine, thereby further improves the dissolution rate and the bioavailability of medicine.Poloxamer can influence the transhipment of medicine in cell, and the mechanism more complicated be it is generally acknowledged, poloxamer can make enterokinesia slack-off, and the holdup time of medicine in gastrointestinal tract is long, and absorbing increases, thereby improves bioavailability of medicament.Tween it is generally acknowledged that as the mechanism of the absorption enhancer of medicine tween can slip into cell membrane, and becomes as a whole with it, thereby can change little viscosity of cell, makes losing of cell hydrophilic bilayer; Its special component in can the dissolved cell film, the composition by the local cells film changes proteic 26S Proteasome Structure and Function, and then suppresses the outer heat-extraction system of top polarization, thus the permeability of increase medicine in intestinal further improves bioavailability of medicament.
More specifically, these specific enteric coatel tablets are got by following preparation method preparation, and this preparation method may further comprise the steps:
1) preparation label:, make the thymosin mixture with thymosin, mannitol, microcrystalline Cellulose, poloxamer, cross-linked pvp and carboxymethyl starch sodium mix homogeneously; Biotin is dissolved in the ethanol, adds Tween 80, mix homogeneously, and make soft material with above-mentioned thymosin mixture is granulated and dry; Add magnesium stearate and micropowder silica gel then, mix homogeneously, tabletting obtains label;
2) preparation coating solution: enteric material is dissolved with ethanol, and mix homogeneously obtains coating solution;
3) coating solution of preparation coating: the label of step 1) preparation put spray step 2), the weight that coating is increased accounts for the 8-10% of label weight, obtains enteric coatel tablets.
The advantage of enteric coatel tablets of the present invention specifically has:
1, dosage is little, the bioavailability height.Adopt biotin as coenzyme, increase the permeability of thymosin in intestinal, improve bioavailability; Adopt Tween 80 and poloxamer to make up in certain proportion, improved the bioavailability of thymosin greatly as absorption enhancer.
2, safety is good.As the surfactant of absorption enhancer, consumption is less, in safety range or in clinical practice, still there is no toxic reaction and stimulation in toxicological test.
3, conveniently take, carry, transport.Dosage form is the oral enteric sheet, has avoided the shortcoming of the inconvenience of injection type administration in the past.
4, cost is lower.Excipient substance of the present invention all is common medicinal adjuvants, produces simply, is fit to China's national situation.
In the third aspect, the invention provides the preparation of drug combination method that the invention provides first aspect present invention, it comprises thymosin and the blended process of biotin.For example, this preparation method can comprise thymosin and the biotin process by mixed shared in the relative medicine compositions.
Aspect the 4th, the invention provides the preparation method of the pharmaceutical preparation of second aspect present invention, it comprises thymosin, biotin and the blended process of pharmaceutically acceptable adjuvant.For example, this preparation method can comprise synthetic thymosin, biotin and the pharmaceutically acceptable adjuvant process by mixed shared in the relative medicine preparation.In a specific embodiment, the preparation method of pharmaceutical preparation comprises: 1) preparation label; 2) preparation coating solution; With 3) coating.
Aspect the 5th, the invention provides the described pharmaceutical composition of first aspect present invention is used for the medicine of lowly relevant disease of chronic hepatitis, viral hepatitis, liver cirrhosis, constitutional or Secondary cases T lymphocyte defective disease, autoimmune disease, cellular immune function or neoplastic disease auxiliary therapy in preparation application.The dosage of administration and form are generally determined according to patient's concrete condition (as age, body weight, sex, sick time, health etc.) by the doctor.As with enteric coatel tablets form oral administration, in the thymosin in pharmaceutical composition or the pharmaceutical preparation, the dosage of administration is 1-50mg thymosin/every adult patient, is preferably 2-30mg, more preferably 10-25mg.Form of medication is determined according to the dosage form of various pharmaceutical preparatioies, the form of medication that is fit to has oral, non-intestinal injection, mucosa, muscle, intravenous, subcutaneous, ophthalmic, Intradermal or through form of medication such as skins, the form of medication of preferred oral of the present invention and injection, especially preferred oral form.
For the ease of understanding, below will present invention is described by specific embodiment.It needs to be noted that these descriptions only are exemplary descriptions, do not constitute limitation of the scope of the invention.According to the argumentation of this description, many modifications of the present invention have been obviously all concerning one of ordinary skill in the art.In addition, the present invention has quoted existing open source literature, and these documents are in order more clearly to describe the present invention, and their full text content is all included this paper in, just looks like that repeated description is the same excessively in this article for their full text.
The specific embodiment
To provide specific embodiment below the present invention, and wherein have the not detailed part can be with reference to the content in prior aries such as " the capsular developments of thymosin " such as Chinese patent application 200610021429, Chen Bushi etc. " thymosin sheet enteric coating prescription ", simple scorching woods or textbook, the test handbook.Hereinafter, as do not have other definition, " compound thymosin enteric coatel tablets " refer to the enteric coatel tablets that contain thymosin and biotin.
The preparation of embodiment one, compound thymosin enteric coatel tablets
Prescription is formed:
Preparation method:
1. preparation label
Thymosin in the prescription, mannitol, microcrystalline Cellulose, poloxamer, cross-linked pvp, carboxymethyl starch sodium are crossed 65 mesh sieves respectively, standby.Will cross the adjuvant mix homogeneously of sieve, the adjuvant equivalent that will cross the thymosin that sieves and the mix homogeneously then mix homogeneously that progressively increases.Biotin is dissolved in the 50ml ethanol, and the tween 80 that adds recipe quantity is dissolved into uniform solution.As binding agent, make soft material with this alcoholic solution, 20 mesh sieves are granulated, drying.After the intermediate detection is qualified,, add the magnesium stearate and the micropowder silica gel mix homogeneously of recipe quantity, tabletting with 18 mesh sieve granulate.
2. preparation coating solution
Adopt ethanol to dissolve enteric material, mix homogeneously obtains coating solution
3. art for coating
Getting label puts in the coating pan, regulating inlet temperature is 65-75 ℃, and outlet temperature is 30-40 ℃, opens coating pan, regulating rotating speed is 15 rev/mins, above-mentioned coating solution is sprayed into spray gun, and the weightening finish of control enteric coating accounts for label 8-10%, insulation 10min, obtain enteric coated tablet, after quality inspection is qualified, use aluminium-plastic bubble plate packing, promptly get the thymosin enteric coatel tablets.
The pharmacodynamics test of embodiment two, compound thymosin enteric coatel tablets
The thymosin enteric coatel tablets are to the influence of mice E garland formation rate.
1, experiment material
1.1 animal: Kunming mouse, ♀ ♂ half and half, body weight 22 ± 2g is provided by Xi'an Jiaotong University Medical College's Experimental Animal Center.The certification of fitness: the moving card of Shan doctor word 08-18 number.
1.2 medicine:
Hydrocortisone acetate injection (specification: 5ml:25mg, manufacturer: Dandong doctor's wound Pharmaceutical Co., Ltd, 070305), injection liquid of thymic peptide alpha 1 specification: 2ml:20mg lot number:, manufacturer: Xi'an Di Sai Bioceuticals Inc., 071220), thymosin enteric coated capsule (specification: 5mg lot number:, 061108), compound thymosin enteric coatel tablets manufacturer: ShangHai BaoLong Pharmacy Co., Ltd, lot number:.
2. test method
Be taken at live 70 of the healthy Kunming mouses in a week of laboratory, be divided into 6 groups at random, every group 10, be respectively the normal control group, negative control group (0.5%CMC-Na solution), positive controls (injection liquid of thymic peptide alpha 1,3mg/kg), thymosin group (0.5%CMC-Na liquid, dosage is 6.0mg thymosin/kg), the heavy dose of group of compound thymosin (0.5%CMC-Na liquid, dosage is 6.0mg thymosin/kg and 0.15mg biotin/kg), dosage group (0.5%CMC-Na liquid in the compound thymosin, dosage is 3.0mg thymosin/kg and 0.075mg biotin/kg), (0.5%CMC-Na liquid, dosage are 1.5mg thymosin/kg and 0.0375mg biotin/kg) to compound thymosin small dose group.The preparation of immunocompromised mice by every day 10mg dosage give the subcutaneous injection hydrocortisone, continuous 7 days.Then, except that the positive controls lumbar injection, all the other respectively organize gastric infusion.Successive administration seven days was got blood and is tested on the 8th day.Adopt the E garland to form test, see 200 lymphocytes of E garland counting, calculate garland and form percentage rate.
Concrete result of the test sees Table 1
The compound thymosin enteric coatel tablets of table 1 are to the influence of mice E garland formation rate (x ± s)
Annotate: compare with negative control group:
*P＜0.01,
*P＜0.05,
* *P＜0.001
Experimental result shows, the function that the big or middle dosage group of compound thymosin has obvious enhancing and regulates cellular immunization, small dose group is compared with negative control group does not have evident difference, and middle dosage group and high dose group all can significantly improve the E garland formation rate (P＜0.01) of immunocompromised mice, and this dosage that illustrates that also the garland of the mice of immunocompromised forms percentage rate and thymosin presents positive correlation.It should be noted that the thymosin group compares with negative control group, E garland formation rate does not have tangible significant difference; And compound thymosin of the present invention has just had the function of significant adjusting cellular immunization when middle dosage; Compound thymosin of the present invention is when heavy dose, and its drug effect even suitable with the injection type of positive control although large usage quantity is considered oral convenience and safety, more has application prospect.
Claims (12)
1, a kind of pharmaceutical composition, it comprises thymosin and biotin, preferably it is made up of thymosin and biotin.
2, pharmaceutical composition according to claim 1, wherein the weight ratio of thymosin and biotin is 1-50:0.01-2.0, is preferably 2-30:0.05-1.0.
3, pharmaceutical composition according to claim 1 and 2, wherein thymosin by animal extract, chemosynthesis or the genetic engineering preparation, preferred thymosin is thymosin.
4, a kind of pharmaceutical preparation, it comprises arbitrary described pharmaceutical composition and the pharmaceutically acceptable adjuvant of claim 1-3.
5, pharmaceutical preparation according to claim 4, it is tablet, capsule, injection or injection lyophilized powder.
6, pharmaceutical preparation according to claim 5, it is enteric coatel tablets.
7, pharmaceutical preparation according to claim 6 contains 1-50mg thymosin and 0.01-2.0mg biotin in it is characterized in that every, preferably contains 2-30mg thymosin and 0.05-1.0mg biotin.
8, according to claim 5 or 6 described pharmaceutical preparatioies, it contains pharmaceutic adjuvant and enteric-coating material, described pharmaceutic adjuvant be selected from can be compatible with active component pharmaceutically acceptable filler, absorption enhancer or enzyme inhibitor, disintegrating agent, lubricant, wetting agent or binding agent in one or more.
9, pharmaceutical preparation according to claim 8, wherein absorption enhancer is selected from one or more of fatty acid, cholic acid and salt thereof, oligochitosan, carbomer, poloxamer, tween 80, sodium lauryl sulphate, and preferred absorption enhancer is the combination of tween 80 and poloxamer.
10, the arbitrary described pharmaceutical composition of claim 1-3 is used for preventing and/or treating the application of the medicine of lowly relevant disease of chronic hepatitis, viral hepatitis, liver cirrhosis, constitutional or Secondary cases T lymphocyte defective disease, autoimmune disease, cellular immune function or neoplastic disease auxiliary therapy in preparation.
11, a kind of thymosin enteric coatel tablets, it contains thymosin, Tween 80 and poloxamer, and wherein the weight ratio of Tween 80 and poloxamer is 1:1-20, is preferably 1:8, and wherein the weight ratio of poloxamer and thymosin is 0.2-20:1.
12, enteric coatel tablets according to claim 11, it is got by the preparation method preparation that may further comprise the steps:
1) preparation label:, make the thymosin mixture with thymosin, mannitol, microcrystalline Cellulose, poloxamer, cross-linked pvp and carboxymethyl starch sodium mix homogeneously; Biotin is dissolved in the ethanol, adds Tween 80, mix homogeneously, and make soft material with above-mentioned thymosin mixture is granulated and dry; Add magnesium stearate and micropowder silica gel then, mix homogeneously, tabletting obtains label;
2) preparation coating solution: enteric material is dissolved with ethanol, and mix homogeneously obtains coating solution;
3) coating solution of preparation coating: the label of step 1) preparation put spray step 2), the weight that coating is increased accounts for the 8-10% of label weight, obtains enteric coatel tablets.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102228680A (en) * | 2011-06-14 | 2011-11-02 | 中国人民解放军第三○二医院 | Thymosin phospholipids/bile salt compound micelle and preparation method and preparation thereof |
| CN102579347A (en) * | 2012-03-02 | 2012-07-18 | 海南灵康制药有限公司 | Thymalfasin liposome preparation for injecting |
| US20180049987A1 (en) * | 2015-01-12 | 2018-02-22 | Enteris Biopharma, Inc. | Solid Oral Dosage Forms |
| CN111297820A (en) * | 2020-03-25 | 2020-06-19 | 哈高科白天鹅药业集团有限公司 | Thymosin enteric-coated tablet and preparation method thereof |
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| CN1151839C (en) * | 2000-06-21 | 2004-06-02 | 南京铁道医学院 | In-colon release-controlled thymopeptide capsule and process for extracting and separating thymopeptide |
| CN1193790C (en) * | 2002-07-01 | 2005-03-23 | 蔡海德 | Thymosin composition injection and its prepn |
| EP1978997A1 (en) * | 2005-12-22 | 2008-10-15 | Apollo Life Sciences Limited | Transdermal delivery of pharmaceutical agents |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102228680A (en) * | 2011-06-14 | 2011-11-02 | 中国人民解放军第三○二医院 | Thymosin phospholipids/bile salt compound micelle and preparation method and preparation thereof |
| CN102228680B (en) * | 2011-06-14 | 2013-02-27 | 中国人民解放军第三0二医院 | Thymosin phospholipids/bile salt compound micelle and preparation method and preparation thereof |
| CN102579347A (en) * | 2012-03-02 | 2012-07-18 | 海南灵康制药有限公司 | Thymalfasin liposome preparation for injecting |
| CN102579347B (en) * | 2012-03-02 | 2013-03-06 | 海南灵康制药有限公司 | Thymalfasin liposome preparation for injecting |
| US20180049987A1 (en) * | 2015-01-12 | 2018-02-22 | Enteris Biopharma, Inc. | Solid Oral Dosage Forms |
| CN111297820A (en) * | 2020-03-25 | 2020-06-19 | 哈高科白天鹅药业集团有限公司 | Thymosin enteric-coated tablet and preparation method thereof |
| CN113230386A (en) * | 2021-03-07 | 2021-08-10 | 合肥天汇孵化科技有限公司 | Thymalfasin composition and application thereof |
| CN113230386B (en) * | 2021-03-07 | 2022-04-12 | 合肥天汇孵化科技有限公司 | Thymalfasin composition and application thereof |
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Application publication date: 20090311 Assignee: Disai Bio Pharmaceutical Co.,Ltd. Xian Assignor: Wu Jianzhong Contract record no.: 2014610000081 Denomination of invention: Efficient thymosin enteric-coated tablets and thymosin for injection Granted publication date: 20110907 License type: Exclusive License Record date: 20140424 |
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Denomination of invention: Efficient thymosin enteric coated tablets and thymosin for injection Effective date of registration: 20220505 Granted publication date: 20110907 Pledgee: Industrial and Commercial Bank of China Limited Xi'an Lianhu road sub branch Pledgor: Disai Bio Pharmaceutical Co.,Ltd. Xian Registration number: Y2022610000218 |
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Denomination of invention: Highly effective Thymosin enteric coated tablets and Thymosin for injection Effective date of registration: 20230616 Granted publication date: 20110907 Pledgee: Industrial and Commercial Bank of China Limited Xi'an Weiyang Branch Pledgor: Disai Bio Pharmaceutical Co.,Ltd. Xian Registration number: Y2023610000455 |
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