CN1232301C - Compound preparation of valvciclovir HCL and Pidotimod - Google Patents
Compound preparation of valvciclovir HCL and Pidotimod Download PDFInfo
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- CN1232301C CN1232301C CN 200410006240 CN200410006240A CN1232301C CN 1232301 C CN1232301 C CN 1232301C CN 200410006240 CN200410006240 CN 200410006240 CN 200410006240 A CN200410006240 A CN 200410006240A CN 1232301 C CN1232301 C CN 1232301C
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- Prior art keywords
- pidotimod
- compound preparation
- hydrochloride
- present
- virus
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- 229960001163 pidotimod Drugs 0.000 title claims abstract description 21
- UUTKICFRNVKFRG-WDSKDSINSA-N (4R)-3-[oxo-[(2S)-5-oxo-2-pyrrolidinyl]methyl]-4-thiazolidinecarboxylic acid Chemical compound OC(=O)[C@@H]1CSCN1C(=O)[C@H]1NC(=O)CC1 UUTKICFRNVKFRG-WDSKDSINSA-N 0.000 title claims abstract description 11
- 150000001875 compounds Chemical class 0.000 title abstract description 5
- -1 compound valaciclovir hydrochloride Chemical class 0.000 claims abstract description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 17
- 230000000694 effects Effects 0.000 abstract description 14
- 241000700605 Viruses Species 0.000 abstract description 10
- 201000010099 disease Diseases 0.000 abstract description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 4
- 230000036737 immune function Effects 0.000 abstract description 4
- 230000001105 regulatory effect Effects 0.000 abstract description 2
- ZCDDBUOENGJMLV-QRPNPIFTSA-N Valacyclovir hydrochloride Chemical compound Cl.N1C(N)=NC(=O)C2=C1N(COCCOC(=O)[C@@H](N)C(C)C)C=N2 ZCDDBUOENGJMLV-QRPNPIFTSA-N 0.000 abstract 1
- 230000035876 healing Effects 0.000 abstract 1
- 229940064636 valacyclovir hydrochloride Drugs 0.000 abstract 1
- 208000019802 Sexually transmitted disease Diseases 0.000 description 14
- 206010059313 Anogenital warts Diseases 0.000 description 10
- 229960004150 aciclovir Drugs 0.000 description 10
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 10
- 231100000915 pathological change Toxicity 0.000 description 6
- 230000036285 pathological change Effects 0.000 description 6
- 102000053602 DNA Human genes 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 5
- HDOVUKNUBWVHOX-QMMMGPOBSA-N Valacyclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCOC(=O)[C@@H](N)C(C)C)C=N2 HDOVUKNUBWVHOX-QMMMGPOBSA-N 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 229940093257 valacyclovir Drugs 0.000 description 5
- 241000700584 Simplexvirus Species 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000000840 anti-viral effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 230000002924 anti-infective effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 208000022844 Bacterial Sexually Transmitted disease Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- 206010018612 Gonorrhoea Diseases 0.000 description 1
- 208000001688 Herpes Genitalis Diseases 0.000 description 1
- 241000701806 Human papillomavirus Species 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 241000710185 Mengo virus Species 0.000 description 1
- 208000035286 Spontaneous Remission Diseases 0.000 description 1
- OIRDTQYFTABQOQ-UHTZMRCNSA-N Vidarabine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O OIRDTQYFTABQOQ-UHTZMRCNSA-N 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 201000004946 genital herpes Diseases 0.000 description 1
- 208000001786 gonorrhea Diseases 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000002434 immunopotentiative effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000002212 purine nucleoside Substances 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000006379 syphilis Diseases 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 208000000143 urethritis Diseases 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 229960003636 vidarabine Drugs 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 208000028110 viral sexually transmitted disease Diseases 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a compound valaciclovir hydrochloride and pidotimod preparation for treating venereal diseases, which is prepared from 100 to 600 mg of valacyclovir hydrochloride and 200 to 1600 mg of pidotimod. The compound preparation provided by the present invention not only can resist viruses, have the function of regulating an immune function simultaneously, treat venereal diseases, have good effect on a clinic healing rate, but also can lower a recurrence rate.
Description
Technical field
The present invention relates to a kind of Wannailuowei hydrochloride and pidotimod compound preparation, be used for the treatment of sexually transmitted disease (STD).
Background technology
Sexually transmitted disease (STD) is popular in China's large tracts of land in recent years, from 1991 to calendar year 2001 average growth rate per annum be 19.30%, over nearly 2 years, the trend that grows in intensity is arranged also.In the treatment of sexually transmitted disease (STD),, use the existing good effect of antibiotic to bacterial sexually transmitted disease (STD)s such as gonorrhea, nongonococcal urethritis, syphilis; But the sexually transmitted disease (STD) to viruses such as condyloma acuminatum, genital herpes cause still lacks effective radical cure means at present.
Comparatively general with valaciclovir in the sick virus drugs of the resistance of clinical use, valaciclovir is the precursor of acyclovir, enters to be hydrolyzed into acyclovir in the body and to suppress virus.Inhibitory action to herpes simplex virus I (HSV-I) and herpes simplex virus I I (HSV-II) is strong, and other viral sexually transmitted disease (STD)s are also had the good restraining effect.The mechanism of action of valaciclovir is the synthetic of limiting virus DNA and suppress it and duplicate, thereby reach the purpose that reduces virus from measuring, but finally removing virus still needs body's immunological function to realize target, if have a kind of can antiviral, can also take into account simultaneously the medicine that the patient immune function regulates, the anti-infective therapy that is used for the patient will obtain the effect of " work along both lines, curative effect is better ".
Summary of the invention
The object of the present invention is to provide a kind of can antiviral, also have the medicine that immunologic function is regulated simultaneously.
Technical solution of the present invention is: a kind of Wannailuowei hydrochloride and pidotimod compound preparation, and it consists of:
Wannailuowei hydrochloride: 100-600mg
Pidotimod: 200-1600mg
Below illustrate the principle of compound preparation of the present invention from pharmacology, pharmacokinetics and clinical effectiveness:
One, pharmacology
The oral back of Wannailuowei hydrochloride is absorbed rapidly and is converted into acyclovir, its main mechanism is the synthetic of limiting virus DNA and suppress it and duplicate, and acyclovir is a kind of synthetic acyclic purine nucleosides compounds, has the effect that suppresses multiple DNA (deoxyribonucleic acid).Particularly for herpesvirus, render a service stronger 160 times than vidarabine, and very low to human toxicity.
Pidotimod (Pidotimod) commodity by name ten thousand are suitable peaceful, dipeptide immunopotentiating agent for a kind of chemosynthesis, can react by too many levels enhancing body anti-infectious immunity, significantly improve every immune indexes of the low patient of immune level, he can correct the CD4/CD8 ratio and be inverted, therefore the secretion that activate the NK cell, stimulates IL-2, IFN-γ can not only be used for bacterial infection, also can be used for the treatment and the auxiliary treatment of viral infection; The foreign study document shows that pidotimod is all effective to mengo virus, herpes simplex virus and influenza virus.
Studies show that two medicines all possess antiviral effect, its compound preparation can not only suppress duplicating of virus from measuring, and finally reaches the purpose of removing virus by the endogenous immune response of transferring body.
Two, pharmacokinetics
The oral back of Wannailuowei hydrochloride is absorbed rapidly and is converted into acyclovir, and parent acyclovir peak time is 0.88-1.75hr in the blood.Oral administration biaavailability is 67 ± 13%, is 3-5 times of acyclovir.Widely distributed after the Wannailuowei hydrochloride oral absorption, can be distributed in all 14 kinds of tissues, wherein concentration is the highest in stomach, small intestinal, kidney, liver, lymph node and the skin histology, and the concentration of cerebral tissue is minimum.Be converted into acyclovir rapidly up hill and dale in vivo after the Wannailuowei hydrochloride oral absorption, metabolite is mainly got rid of from urine, wherein the acyclovir Lip river accounts for 46%-59%, and 8-hydroxyl-9-guanine accounts for 25%-30%, and 9-hydroxyl methoxy guanine accounts for 11%-12%.The elimination of parent acyclovir is single-phase behind the oral administration, and the half-life is 2.86 ± 0.39hr.
Pidotimod sheet (Wan Shining) oral absorption is rapid, and blood Chinese medicine peak time is about 1.9 hours, and the elimination half-life is about 1.6 hours, and irrelevant with dosage and approach, and oral administration biaavailability is 42-44%, and plasma clearance is 5L/h.Not metabolism is in vivo mainly discharged from kidney with prototype, and repeat administration is savings or self-induction phenomenon not.
The specific embodiment
Wannailuowei hydrochloride of the present invention and pidotimod compound preparation, it consists of:
Wannailuowei hydrochloride: 100-600mg
Pidotimod: 200-1600mg.
By above-mentioned composition, add pharmaceutically acceptable additives again, make tablet, oral, a twice-daily.
Embodiment sees the following form
Table 1 embodiment
Further specify the effect of compound preparation of the present invention below by curative effect report.
Wannailuowei hydrochloride and the report of pidotimod compound preparation treatment condyloma acuminatum curative effect
Condyloma acuminatum is the common sexually transmitted disease (STD) that is caused by the human papillomavirus, and its sickness rate is in rising trend, and according to incompletely statistics, condyloma acuminatum in 1999 have accounted for the 20-31% of sexually transmitted disease (STD).Adopt valaciclovir of the present invention and pidotimod compound preparation treatment condyloma acuminatum patient, its result is as follows: purpose: observe Wannailuowei hydrochloride and the pidotimod compound preparation clinical remission rate for the condyloma acuminatum patient
Method:
1, case: select outpatient service to be diagnosed as condyloma acuminatum patient 40 examples, be divided into treatment group and matched group at random, two groups of there was no significant differences on age, sex and disease severity, medical history is 6-8 month.All cases are all made a definite diagnosis through DNA or pathological examination.
2, Therapeutic Method:
The treatment group: Wannailuowei hydrochloride and pidotimod compound preparation (wherein hydrochloric valaciclovir 300mg, pidotimod 800mg), oral, twice on the one.
Matched group: Wannailuowei hydrochloride 300mg, oral, twice on the one.
Treatment group and matched group are 12 days the course of treatment.
4, curative effect determinate standard
Recovery from illness: all pathological changes all disappear, and recover normal appearance; Produce effects: 70% above pathological changes disappears; Effectively: 30% above pathological changes disappears, and 70% following pathological changes does not disappear; Invalid: the pathological changes less than 30% that disappears, former pathological changes no change, zero growth; Followed up a case by regular visits to 2 months, and reappeared disease and decrease to recurring.The result:
The curative effect of table 2 liang group condyloma acuminatum relatively
| The example number | Recovery from illness | Produce effects | Effectively | Invalid | Effective percentage (%) | |
| Matched group | 20 | ?7 | ?11 | ?1 | ?0 | ?95 |
| Experimental group | 20 | ?16 | ?3 | ?1 | ?0 | ?100 |
Followed up a case by regular visits to 2 months, experimental group loses visits 3 examples, and matched group loses visits 2 examples
The recurrence of table 3 liang group condyloma acuminatum relatively
| Group | The example number | Relapse rate example number (%) | Relapse rate example number (%) not |
| Matched group | 18 | ?13(72.2％) | 5(27.8％) |
| Experimental group | 17 | ?2(11.7％) | 15(88.2％) |
Side effect:
Two groups all have case symptom dizzy, that feel sick to occur, but not serious, but spontaneous remission.
Conclusion:
The Therapeutic Method of condyloma acuminatum is a lot of at present, but very easily recurrence, and cause of recurrence is moist or again the subinfection except that pudendum, is exactly that treatment is thorough inadequately.Using the treatment of Wannailuowei hydrochloride of the present invention and pidotimod compound preparation not only has good effect on clinical cure rate, and can reduce relapse rate (p＜0.05).
Claims (1)
1, a kind of Wannailuowei hydrochloride and pidotimod compound preparation is characterized in that it consists of:
Wannailuowei hydrochloride: 100-600mg
Pidotimod: 200-1600mg.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410006240 CN1232301C (en) | 2004-03-17 | 2004-03-17 | Compound preparation of valvciclovir HCL and Pidotimod |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410006240 CN1232301C (en) | 2004-03-17 | 2004-03-17 | Compound preparation of valvciclovir HCL and Pidotimod |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1562342A CN1562342A (en) | 2005-01-12 |
| CN1232301C true CN1232301C (en) | 2005-12-21 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410006240 Expired - Fee Related CN1232301C (en) | 2004-03-17 | 2004-03-17 | Compound preparation of valvciclovir HCL and Pidotimod |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1232301C (en) |
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2004
- 2004-03-17 CN CN 200410006240 patent/CN1232301C/en not_active Expired - Fee Related
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| Publication number | Publication date |
|---|---|
| CN1562342A (en) | 2005-01-12 |
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| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: HAN ZHIQIANG Free format text: FORMER OWNER: TAIYANGSHI (TANGSHAN) PHARMACEUTICAL CO. LTD. Effective date: 20060324 |
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| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20060324 Address after: 063020 Torch Road, Tangshan City hi tech Development Zone, Hebei Patentee after: Han Zhiqiang Address before: 063020 Torch Road, Tangshan City hi tech Development Zone, Hebei Patentee before: Taiyangshi (Tangshan) Pharm Ind Co., Ltd. |
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| EE01 | Entry into force of recordation of patent licensing contract |
Assignee: Taiyangshi (Tangshan) Pharm Ind Co., Ltd. Assignor: Han Zhiqiang Contract fulfillment period: 2007.09.05 to 2024.01.16 Contract record no.: 2007990000066 Denomination of invention: A compound preparation of vanaiclovir hydrochloride and pidotimod Granted publication date: 20051221 License type: Exclusive license Record date: 20071012 |
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| LIC | Patent licence contract for exploitation submitted for record |
Free format text: EXCLUSIVE LICENCE; TIME LIMIT OF IMPLEMENTING CONTACT: 2007.9.5 TO 2024.1.16 Name of requester: TAIYANGSHI (TANGSHAN) PHARMACEUTICAL CO. LTD. Effective date: 20071012 |
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| EE01 | Entry into force of recordation of patent licensing contract |
Assignee: Taiyangshi (Tangshan) Pharm Ind Co., Ltd. Assignor: Han Zhiqiang Contract fulfillment period: 2009.10.20 to 2014.10.19 Contract record no.: 2009990001300 Denomination of invention: A kind of valaciclovir hydrochloride and Pi do Maude compound preparation Granted publication date: 20051221 License type: General permission Record date: 20091130 Assignee: Taiyangshi (Tangshan) Pharm Ind Co., Ltd. Assignor: Han Zhiqiang Contract fulfillment period: 2009.12.16 to 2026.5.30 Contract record no.: 2009990001331 Denomination of invention: A kind of valaciclovir hydrochloride and Pi do Maude compound preparation Granted publication date: 20051221 License type: Exclusive license Record date: 20091217 |
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Free format text: COMMON LICENSE; TIME LIMIT OF IMPLEMENTING CONTACT: 2009.10.20 TO 2014.10.19; CHANGE OF CONTRACT Name of requester: TAIYANGSHI (TANGSHAN) PHARMACEUTICAL CO. LTD. Effective date: 20091130 Free format text: EXCLUSIVE LICENSE; TIME LIMIT OF IMPLEMENTING CONTACT: 2009.12.16 TO 2026.5.30; CHANGE OF CONTRACT Name of requester: TAIYANGSHI (TANGSHAN) PHARMACEUTICAL CO. LTD. Effective date: 20091217 |
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Owner name: SUNSTONE (TANGSHAN) PHARMA CO., LTD. Free format text: FORMER OWNER: HAN ZHIQIANG Effective date: 20101125 |
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Free format text: CORRECT: ADDRESS; FROM: 063020 TORCH ROAD, NEW + HIGH TECHNOLOGY DEVELOPMENT ZONE, TANGSHAN CITY, HEBEI PROVINCE TO: 063020 NO.139, TORCH ROAD, NEW + HIGH TECHNOLOGY DEVELOPMENT ZONE, TANGSHAN CITY, HEBEI PROVINCE |
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Effective date of registration: 20101125 Address after: 063020 Torch Road, Tangshan City hi tech Development Zone, Hebei 139, China Patentee after: Taiyangshi (Tangshan) Pharm Ind Co., Ltd. Address before: 063020 Torch Road, Tangshan City hi tech Development Zone, Hebei Patentee before: Han Zhiqiang |
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