CN103230404A - Novel use of adefovir dipivoxil or medicinal salt thereof - Google Patents
Novel use of adefovir dipivoxil or medicinal salt thereof Download PDFInfo
- Publication number
- CN103230404A CN103230404A CN2013101765190A CN201310176519A CN103230404A CN 103230404 A CN103230404 A CN 103230404A CN 2013101765190 A CN2013101765190 A CN 2013101765190A CN 201310176519 A CN201310176519 A CN 201310176519A CN 103230404 A CN103230404 A CN 103230404A
- Authority
- CN
- China
- Prior art keywords
- tenofovir
- pyrrole furan
- medicine
- ester
- pharmaceutical salts
- 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.)
- Pending
Links
Abstract
The invention relates to novel use of adefovir dipivoxil or a medicinal salt thereof, and particularly relates to application in preparation of a drug for treating influenza A or B, and application in preparation of the drug for preventing the influenza A or B.
Description
Technical field
The present invention relates to the new purposes of tenofovir two pyrrole furan esters or its pharmaceutical salts, comprise the purposes on the various influenzas of control.
Background technology
Fumaric acid tenofovir two pyrrole furan ester (fovir disoproxil fumarate, TDF), its chemistry is by name: 9-[(R)-two [[(isopropoxy carbonyl) oxygen base] methoxyl group] phosphinyls of 2-[[] methoxyl group]-propyl group] adenine fumarate (1: 1), its structure is as shown in the formula 1:
Formula 1
Fumaric acid tenofovir two pyrrole furan esters are by the research and development of U.S. Glead Scierices company, are to be used for the treatment of the ucleotides reverse transcription inhibitor that HIV infects.It is applicable to other antiretroviral drugs and share that treatment HIV-1 infects.
Have in the research that 186 routine HIV-1 the infecteds participate at one, patient accepts a kind of in placebo or fumaric acid tenofovir 3 kinds of dosage of two pyrrole furan esters (75,150 or 300 milligrams), unites other antiretroviral drugs, 24～48 weeks of medication.The time-weighted average of the horizontal logarithm value of 24 when week blood plasma HIV-1RNA is changed to placebo group than basic value and increases 0.02, and fumaric acid tenofovir two pyrrole furan ester treatment groups lower 0.58.And reaction is continuing always, and this product group lowers 0.62 than being changed to of basic value during to 48 weeks.Studies show that the most of strain to efabirenz sensitivity descends has response to fumaric acid tenofovir two pyrrole furan esters.
It should be noted that at treatment HIV-1 and infect clinically that fumaric acid tenofovir two pyrrole furan esters should not share with TRUVADA or ATRIPLA.
In addition, fumaric acid tenofovir two pyrrole furan esters also have the relevant report at treatment HBV.In the 58th hepatopathy annual meeting of U.S. AASLD in 2007, German scholar van Bommel etc. has reported after using lamivudine (LAM) drug resistance, use the 10 routine chronic hepatitis B patients that drug resistance appears in adefovir ester (ADV) again instead, carried out surpassing the fumaric acid tenofovir two pyrrole furan ester single therapies of December.Research conclusion shows: fumaric acid tenofovir two pyrrole furan ester single therapies all have significant antivirus action to the relevant HBV-DNA that reaches the different drug resistance variant sites that merge of ADV.
The tenofovir two pyrrole furan ester officinal salts that gone on the market at present are fumarate, but other pharmaceutical salts of tenofovir two pyrrole furan esters also have same pharmaceutically active, and these salt comprise: tenofovir two pyrrole furan ester succinates, tenofovir two pyrrole furan ester L-tartrates, tenofovir two pyrrole furan ester oxalates, tenofovir two pyrrole furan ester saccharates, tenofovir two pyrrole furan ester citrates, tenofovir two pyrrole furan ester Salicylates, tenofovir two pyrrole furan ester phosphate etc.
To sum up, tenofovir two pyrrole furan esters or its pharmaceutical salts have the application that treatment HIV infects and HBV infects clinically.Yet application is not in other respects seen at present report.
The present invention finds that in research process tenofovir two pyrrole furan esters or its pharmaceutical salts also have good effect in the influenza that control virus causes.
Summary of the invention
The new purposes that the purpose of this invention is to provide tenofovir two pyrrole furan esters or its pharmaceutical salts.
Medicine of the present invention can be made the pharmaceutical preparation that oral administration is used, and also can be made into the pharmaceutical preparation of parenteral administration.
Medicine of the present invention when making each dosage form, contains tenofovir two pyrrole furan esters or its pharmaceutical salts 10～500mg in its pharmaceutical preparation.Preferred tenofovir two pyrrole furan esters or its pharmaceutical salts 50～300mg; Preferred especially tenofovir two pyrrole furan esters or its pharmaceutical salts 300mg.
The content of the above tenofovir two pyrrole furan ester pharmaceutical salts when feeding intake all in the content of tenofovir two pyrrole furan esters, as tenofovir two pyrrole furan ester pharmaceutical salts the inventory content that is converted to tenofovir two pyrrole furan esters be 10-500mg, 50-300mg, 300mg.
Medicine of the present invention as required, also can add the medicine acceptable carrier, and its percentage by weight that accounts for compositions can be 0.1%-99.9%.
Medicine of the present invention, wherein said tenofovir two pyrrole furan ester pharmaceutical salts are selected from: tenofovir two pyrrole furan ester succinates, tenofovir two pyrrole furan ester L-tartrates, tenofovir two pyrrole furan ester oxalates, tenofovir two pyrrole furan ester saccharates, tenofovir two pyrrole furan ester citrates, tenofovir two pyrrole furan ester Salicylates, tenofovir two pyrrole furan ester phosphate, fumaric acid tenofovir two pyrrole furan esters etc., the present invention is most preferred to be: fumaric acid tenofovir two pyrrole furan esters.
The present invention also further provides the application of described medicine in pharmaceutical preparation.Described preparation can be made into any pharmaceutically useful dosage form.These dosage forms comprise: tablet, sugar coated tablet, film coated tablet, enteric coated tablet, capsule, hard capsule, soft capsule, oral liquid, suck agent, granule, electuary, pill, powder, unguentum, sublimed preparation, suspensoid, powder, solution, injection, suppository, ointment, plaster, cream, spray, drop, patch.Preparation of the present invention is preferably peroral dosage form and injection.Wherein peroral dosage form particularly preferably is tablet, capsule, granule, oral liquid.Pharmaceutical composition of the present invention can prepare according to the routine techniques of pharmaceutical preparation, as tenofovir two pyrrole furan esters or its pharmaceutical salts and medicine acceptable carrier are mixed, and by granule processed, tablet, method such as encapsulated is prepared into oral drug preparation.
Preparing such formulations is the conventional method known of those skilled in that art normally.
Preferably, pharmaceutical composition of the present invention, contain in its prescription of per 1000 unit formulations:
This prescription obtains through screening, below is the stability data of screening experiment, respectively the effective ingredient fumaric acid tenofovir two pyrrole furan esters in embodiment 1 tablet and embodiment 3 capsules is carried out study on the stability, and the result is as follows:
As seen from the above table, the effective ingredient of making behind tablet and the capsule does not have great variation.
The new purposes that the purpose of this invention is to provide this medicine.Namely use the various influenzas of medical treatment of the present invention.
According to the difference of virus antigen characteristic and genetic characteristics thereof, influenza virus is divided into the A(first), B(second), C(third) three types.Specifically be classified as follows:
A type (first type) influenza: A type influenza virus energy infected person, fowl, pig, horse, sea dog, whale and other animals, but wild birds is the natural host of this virus.A type influenza virus is always in continuous variation, is divided into different hypotypes according to two kinds of protein on viral top layer.These two kinds of protein are respectively hemagglutinin (HA) and neuraminic acid (NA).Wherein HA has 15 hypotypes, and NA has 9 hypotypes.Two kinds of protein of HA and NA may form multiple combination.Have only several A type influenza virus sub-strains in the crowd, generally to propagate (H1N1, H1N2 and H3N2) at present.Other subtype virus are mainly seen in various animals, H7N7 and the H3N8 type virus that for example can cause herds of horses to infect.The title of A type influenza virus sub-strain is decided according to HA and two kinds of surface layer proteins of NA.For example, H5N1 type virus is made up of HA5 and two kinds of protein of NA1.
Type B (B-mode) influenza: the Type B influenza virus only sees human body usually.Different with A type influenza virus is that this virus can not make a variation rapidly, does not therefore have the hypotype classification.Though the Type B influenza virus can cause influenza in the crowd, this virus can not cause epidemic situation.
C type (third type) influenza: C type influenza virus only can cause human body slight condition of illness to occur, can not cause influenza disease or epidemic situation.C type influenza virus does not have the hypotype classification.
The concrete application in the various influenzas of control of this pharmaceutical composition is as follows:
1) is used for the treatment of the influenza that various street virus cause.B(second for example) type influenza and C(third) the type influenza.
2) be used for the treatment of special influenza, comprising the influenzas such as HN series in SARS, A (first) the type influenza.Wherein, HN series includes H1N1, H1N2, H2N2, H3N2, H3N8, H5N1, H7N7, H7N9, H9N2 etc.
3) be used for the prevention of population infection influenzas such as easy infection crowd, high-risk group.Immunity degradation crowd for example, the crowds such as medical personnel that suffered from the family numbers of patients of influenza and contactee, treatment influenza, pharmaceutical composition of the present invention has the effect of prevention.
The specific embodiment
Further specify the present invention below by several specific embodiments, do not constitute the restriction of the claimed scope of the present invention for the concrete data that relate among the embodiment and operation etc.
Embodiment 1(tablet)
Prescription:
Wherein feed intake if use tenofovir two pyrrole furan ester pharmaceutical salts, then consumption is in tenofovir two pyrrole furan esters.
Method for making: above-mentioned microcrystalline Cellulose, carboxymethyl starch sodium and magnesium stearate were pulverized 100 orders respectively, more than 10 hours, be chilled to room temperature in 100 ℃ of drying under reduced pressure; again with fumaric acid tenofovir two pyrrole furan ester mix homogeneously; dry granulation mechanism grain is pressed into 1000, namely.
Embodiment 2(injection)
Prescription:
Wherein feed intake if use tenofovir two pyrrole furan ester pharmaceutical salts, then consumption is in tenofovir two pyrrole furan esters.
Method for making: fumaric acid tenofovir two pyrrole furan esters are dissolved among the Glycofurol75, add benzyl alcohol then, dissolving adds water to 3ml, after mixed liquor is filtered and is sealed in the 3ml ampoule glass bottle by sterile millipore filter.
Embodiment 3(capsule)
Prescription:
Wherein feed intake if use tenofovir two pyrrole furan ester pharmaceutical salts, then consumption is in tenofovir two pyrrole furan esters.
Method for making: the microcrystalline Cellulose in above-mentioned, carboxymethyl starch sodium were pulverized 100 orders respectively; in 100 ℃ of drying under reduced pressure more than 10 hours; be chilled to room temperature; with fumaric acid tenofovir two pyrrole furan ester mix homogeneously; dry granulation mechanism grain adds magnesium stearate, mixing; be filled in 1000 Capsuleses, namely get described medicament composition capsule.
Embodiment 4(capsule)
Prescription:
Wherein feed intake if use tenofovir two pyrrole furan ester pharmaceutical salts, then consumption is in tenofovir two pyrrole furan esters.
Method for making: consistent with embodiment 3.
Embodiment 5(syrup)
Prescription:
Wherein feed intake if use tenofovir two pyrrole furan ester pharmaceutical salts, then consumption is in tenofovir two pyrrole furan esters.
Method for making: fumaric acid tenofovir two pyrrole furan esters are dissolved in the mixed liquor of glycerol and most of purified water, add sorbitol solution then, add xylitol at last, add purified water to volume required, and mixing, namely.
Other dosage forms of embodiment 6()
Make other dosage forms according to the conventional method on the galenic pharmacy, dispersible tablet for example, is sucked agent, granule, electuary, sublimed preparation, pill, powder, powder, solution etc. at sugar coated tablet, film coated tablet, enteric coated tablet, oral liquid.
The application of the medicine of embodiment 7 embodiment 1-6 in the medicine of preparation treatment first type or influenza B.
Tablet among the embodiment 1 is respectively applied in first type H2N2 influenza virus, the Influenza B virus test, finds that first type H2N2 influenza virus, Influenza B virus all lose activity.
The application of the described medicine of embodiment 8 embodiment 1-6 in the medicine of preparation prevention first type or influenza B.
With the injection among the embodiment 2 be expelled in the experiment poultry with blank group poultry relatively, and contact same H1N1 influenza virus simultaneously, find only to infect the H1N1 influenza less than 15% experiment poultry group, and blank poultry group has 80% to infect the H1N1 influenza approximately.As seen, this medicine has the effect of prevention.
Claims (10)
1. tenofovir two pyrrole furan esters or its pharmaceutical salts application in the medicine of preparation treatment first type or influenza B.
2. tenofovir two pyrrole furan esters or its pharmaceutical salts application in the medicine of preparation prevention first type or influenza B.
3. the described application of claim 1 or claim 2, it is characterized in that, wherein said tenofovir two pyrrole furan ester pharmaceutical salts are selected from: tenofovir two pyrrole furan ester succinates, tenofovir two pyrrole furan ester L-tartrates, tenofovir two pyrrole furan ester oxalates, tenofovir two pyrrole furan ester saccharates, tenofovir two pyrrole furan ester citrates, tenofovir two pyrrole furan ester Salicylates, tenofovir two pyrrole furan ester phosphate, tenofovir two pyrrole furan ester fumarates.
4. the described application of claim 1 or claim 2 is characterized in that, wherein said tenofovir two pyrrole furan ester pharmaceutical salts are fumaric acid tenofovir two pyrrole furan esters.
5. the described application of claim 1 or claim 2 is characterized in that, wherein said medicine contains tenofovir two pyrrole furan esters or its pharmaceutical salts 10～500mg.
6. the described application of claim 1 or claim 2 is characterized in that, wherein said medicine contains tenofovir two pyrrole furan esters or its pharmaceutical salts 50～300mg.
7. the described application of claim 1 or claim 2 is characterized in that, wherein said medicine contains tenofovir two pyrrole furan esters or its pharmaceutical salts 300mg.
8. the described application of claim 1 or claim 2 is characterized in that, contains the medicine acceptable carrier in the wherein said medicine, and its percentage by weight that accounts for compositions is 0.1%-99.9%.
9. the described application of claim 1 or claim 2, it is characterized in that wherein said medicine is selected from: tablet, capsule, oral liquid, suck agent, granule, pill, powder, unguentum, sublimed preparation, powder, injection, suppository, unguentum, spray, drop, patch, drop pill.
10. pharmaceutical composition, contain in its prescription of per 1000 unit formulations:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2013101765190A CN103230404A (en) | 2013-05-14 | 2013-05-14 | Novel use of adefovir dipivoxil or medicinal salt thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2013101765190A CN103230404A (en) | 2013-05-14 | 2013-05-14 | Novel use of adefovir dipivoxil or medicinal salt thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103230404A true CN103230404A (en) | 2013-08-07 |
Family
ID=48878522
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2013101765190A Pending CN103230404A (en) | 2013-05-14 | 2013-05-14 | Novel use of adefovir dipivoxil or medicinal salt thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103230404A (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103536577A (en) * | 2013-10-24 | 2014-01-29 | 福建广生堂药业股份有限公司 | Tenofovir dipivoxil fumarate capsule and preparation method thereof |
| CN103641858A (en) * | 2013-12-31 | 2014-03-19 | 湖南千金湘江药业股份有限公司 | Tenofovir disoproxil fumarate and preparation method thereof |
| CN103705478A (en) * | 2013-12-23 | 2014-04-09 | 浙江华海药业股份有限公司 | Oral tablet containing tenofovir disoproxil fumarate |
| CN104288118A (en) * | 2014-07-08 | 2015-01-21 | 南京卡文迪许生物工程技术有限公司 | Tenofovir disoproxil fumarate tablet and preparation method thereof |
| CN104644598A (en) * | 2014-12-05 | 2015-05-27 | 乐普药业股份有限公司 | Tenofovir disoproxil fumarate tablets |
| CN104739784A (en) * | 2013-12-25 | 2015-07-01 | 辰欣药业股份有限公司 | Method for preparing tenofovir disoproxil fumarate tablet |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1264387A (en) * | 1997-07-25 | 2000-08-23 | 吉里德科学公司 | Nucleotide analog composition and synthesis method thereof |
| CN102198110A (en) * | 2011-05-27 | 2011-09-28 | 杭州科本药业有限公司 | Tenofovir disoproxil fumarate dispersible tablets and preparation method thereof |
-
2013
- 2013-05-14 CN CN2013101765190A patent/CN103230404A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1264387A (en) * | 1997-07-25 | 2000-08-23 | 吉里德科学公司 | Nucleotide analog composition and synthesis method thereof |
| CN102198110A (en) * | 2011-05-27 | 2011-09-28 | 杭州科本药业有限公司 | Tenofovir disoproxil fumarate dispersible tablets and preparation method thereof |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103536577A (en) * | 2013-10-24 | 2014-01-29 | 福建广生堂药业股份有限公司 | Tenofovir dipivoxil fumarate capsule and preparation method thereof |
| CN103705478A (en) * | 2013-12-23 | 2014-04-09 | 浙江华海药业股份有限公司 | Oral tablet containing tenofovir disoproxil fumarate |
| CN103705478B (en) * | 2013-12-23 | 2020-02-07 | 浙江华海药业股份有限公司 | Oral tablet containing tenofovir disoproxil fumarate |
| CN104739784A (en) * | 2013-12-25 | 2015-07-01 | 辰欣药业股份有限公司 | Method for preparing tenofovir disoproxil fumarate tablet |
| CN103641858A (en) * | 2013-12-31 | 2014-03-19 | 湖南千金湘江药业股份有限公司 | Tenofovir disoproxil fumarate and preparation method thereof |
| CN103641858B (en) * | 2013-12-31 | 2016-01-20 | 湖南千金湘江药业股份有限公司 | A kind of tenofovir disoproxil fumarate and preparation method thereof |
| CN104288118A (en) * | 2014-07-08 | 2015-01-21 | 南京卡文迪许生物工程技术有限公司 | Tenofovir disoproxil fumarate tablet and preparation method thereof |
| CN104644598A (en) * | 2014-12-05 | 2015-05-27 | 乐普药业股份有限公司 | Tenofovir disoproxil fumarate tablets |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103230404A (en) | Novel use of adefovir dipivoxil or medicinal salt thereof | |
| CN102438604B (en) | Agent for the prophylaxis and treatment of highly pathogenic infectious diseases | |
| CN102180861A (en) | Bicyclol valine ester as well as preparation method, pharmaceutical composition and application thereof | |
| CN101278938A (en) | Compound preparation of tenofovir and entecavir and its application against hepatitis B virus | |
| US6638915B1 (en) | Anti-viral composition | |
| CN103211826A (en) | Antiviral pharmaceutical composition as well as preparation method and application thereof | |
| JP6916113B2 (en) | Method for Producing Vaccine Pharmaceutical Composition for Oral Administration and Vaccine Pharmaceutical Composition for Oral Administration | |
| CN101287744A (en) | Antiviral compounds | |
| ES2214262T3 (en) | PHARMACEUTICAL FORMULATION CONTAINING LAMIVUDINE. | |
| KR102196711B1 (en) | Pharmatheutical composition comprising Tenofovir disoproxil fumarate for preventing or treating of hepatic fibrosis | |
| TW202034904A (en) | Pharmaceutical composition for antiviral infection and preparation method thereof | |
| JP3002700B2 (en) | Anti-AIDS virus agent | |
| CN107648249B (en) | Application of the desgalactotigonin in the drug for preparing prevention influenza infection | |
| TWI820673B (en) | Brexpiprazole oral film composition, preparation method and use thereof | |
| WO2014129884A2 (en) | Composition with inhibitory effect on viral integrase activity | |
| CN102068425A (en) | Improved oseltamivir phosphate medicinal composition | |
| CN114392239B (en) | Compound tablet of lamivudine, zidovudine and efavirenz and preparation method thereof | |
| Kumar et al. | PHARMACOLOGICAL ACTIVITIES OF MICROSPHERE DRUG USED IN HIV | |
| CN101190935A (en) | Compound used for viral infect | |
| CN104434850A (en) | Oral solid medicine composition containing adefovir dipivoxil | |
| CN105982889B (en) | The pharmaceutical composition and its application of resisiting influenza virus | |
| JPH0551565B2 (en) | ||
| EA030298B1 (en) | Lyophilized preparation of atp and complex of group b vitamins and atp and complex of group b vitamins in the form of injections | |
| CN1327386A (en) | Anti-HIV infection agents and method for treating HIV infection | |
| JPH0551566B2 (en) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20130807 |
|
| RJ01 | Rejection of invention patent application after publication |