CN106491598A - A kind of pharmaceutical preparation of methanesulfonic acid arbidol and preparation method and application - Google Patents
A kind of pharmaceutical preparation of methanesulfonic acid arbidol and preparation method and application Download PDFInfo
- Publication number
- CN106491598A CN106491598A CN201610763671.2A CN201610763671A CN106491598A CN 106491598 A CN106491598 A CN 106491598A CN 201610763671 A CN201610763671 A CN 201610763671A CN 106491598 A CN106491598 A CN 106491598A
- Authority
- CN
- China
- Prior art keywords
- methanesulfonic acid
- arbidol
- solution
- pharmaceutical preparation
- preparation
- 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
- 0 CC1(C=CC=CC1)SCC(N(C)C1=C)=C(*)C1=C(CN(C)*)C(O)=C(C)Br Chemical compound CC1(C=CC=CC1)SCC(N(C)C1=C)=C(*)C1=C(CN(C)*)C(O)=C(C)Br 0.000 description 2
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a kind of pharmaceutical preparation of methanesulfonic acid arbidol and preparation method and application, the pharmaceutical preparation is hydrated methanesulfonic acid arbidol by the one of effective dose and pharmaceutically acceptable excipient is constituted.The pharmaceutical preparation of the present invention is by adopting a hydration methanesulfonic acid arbidol for principal agent, the advantage that 50～100mg/mL is up to using its dissolubility in 25 DEG C of water, methanesulfonic acid arbidol dispersibility in aqueous can be strengthened, to promote drug absorption, the bioavailability of medicine is improved；Preferably one hydration methanesulfonic acid arbidol is present with the form of crystal formation C, and the stability of crystal form is good, it is easy to preserves, meets the requirement of preparation technique.In addition preparation method of the present invention has the advantages that process is simple and easily operated.
Description
Technical field
The invention belongs to pharmaceutical chemistry technical field, and in particular to a kind of pharmaceutical preparation of methanesulfonic acid arbidol and its system
Preparation Method and application.
Background technology
Arbidol hydrochloride (Arbidol Hydrochloride) is taken the lead in developing and listed by Russia, and the medicine is to first
The suppression ratio that type and Influenza B viruss are replicated is respectively 80% and 60%, and there is interferon-induced and immunoregulation effect,
It is mainly used in treating influenza, the upper respiratory tract infection caused by first, Influenza B viruss and concurrent bronchitis, pneumonia
Deng and well-tolerated, Oral Acute Toxicity are low, and medication is safer.
Arbidol hydrochloride belongs to BCS II class medicines, rate-limiting step of its dissolution for drug absorption.The medicine dissolution
Property for readily soluble in methyl alcohol, slightly soluble, almost insoluble in water, dilute hydrochloric acid and sodium hydroxide solution in glacial acetic acid.Arbidol
And its low aqueous solubility of hydrochlorate, shorter half-life cause its bioavailability relatively low.For this purpose, Russia has carried out first sulphur again
The research of sour arbidol, as a result shows that methanesulfonic acid arbidol has preferable resisiting influenza virus curative effect and toxicity is low, more important
Be that the water solublity of methanesulfonic acid arbidol is substantially better than arbidol hydrochloride.However, the amorphous powder of arbidol mesylate
Last easily water suction, stability are poor, not easy to maintain, have had a strong impact on the curative effect of medication using which as pharmaceutically active molecule.
For overcoming this defect, Chinese patent literature CN 102267936A to disclose a kind of methanesulfonic acid arbidol crystal,
Its melting range is 167.5～168.5 DEG C, the XRPD collection of illustrative plates of the crystal 2 θ=10.18 °, 11.88 °, 12.36 °, 14.09 °,
There are characteristic peak, DSC collection of illustrative plates to have near 206.27 DEG C at 14.32 °, 16.85 °, 19.08 °, 20.05 °, 20.10 ° and 36.33 °
One endothermic peak.The stable crystal form of the arbidol mesylate in above-mentioned technology, hygroscopicity are low, easily preserve, but the crystal
Dissolubility in 25 DEG C of water only has 37mg/mL, is still difficult to satisfaction and plays which with the crystal as the medicine of pharmaceutically active molecule
The requirement of curative effect, thus the water solublity of this area methanesulfonic acid arbidol in urgent need to be improved.
Content of the invention
The technical problem to be solved be to overcome water solublity existing for existing methanesulfonic acid arbidol compared with
Poor defect, and then a kind of pharmaceutical preparation comprising the preferable methanesulfonic acid arbidol crystal formation C of water solublity and its preparation side are provided
Method and application.
For this purpose, the present invention realizes that the technical scheme of above-mentioned purpose is：
A kind of pharmaceutical preparation of methanesulfonic acid arbidol, the pharmaceutical preparation by effective dose methanesulfonic acid arbidol and
Pharmaceutically acceptable excipient composition,
Shown in the structure such as formula (I) of the methanesulfonic acid arbidol：
The XRPD collection of illustrative plates that the crystal formation C of the methanesulfonic acid arbidol is represented with the 2 θ ± 0.2 ° angles of diffraction 6.183 °,
7.858°、18.290°、18.566°、21.465°、21.717°、23.934°、24.633°、25.011°、25.617°、
Characteristic diffraction peak is shown at 26.013 ° and 31.382 °.
The XRPD collection of illustrative plates of the crystal formation C of the methanesulfonic acid arbidol has following characteristic diffraction peak：
The DSC collection of illustrative plates of the crystal formation C of the methanesulfonic acid arbidol is that there is at 176.2 DEG C feature melting to absorb in peak value
Peak.
The pharmaceutical preparation is liquid preparation, and the liquid preparation is oral solution, syrup, mixture, Emulsion or note
Penetrate liquid.
The excipient includes one or more in purified water and sweeting agent, aromatic, pH adjusting agent or antioxidant.
The oral solution of every 1000 parts by volume is made up of the following raw material：
Wherein, weight portion is g/mL with the relation of parts by volume.
The sweeting agent includes sucrose, Fructose, Sorbitol, Mannitol, xylitol, sucralose, aspartame, steviosin
Or one or more in saccharin sodium；
The aromatic includes strawberry essence, cherry essence, flavoring banana essence, peach flavor, flavoring orange essence or minty note
One or more in essence；
The pH adjusting agent include citric acid, sodium citrate, lactic acid, sodium lactate, citric acid, sodium citrate, tartaric acid or
One or more in sodium tartrate；
The antioxidant includes the one kind in disodium edetate, sodium pyrosulfite, sodium sulfite, tartaric acid or citric acid
Or it is multiple.
A kind of method for preparing above-mentioned methanesulfonic acid arbidol pharmaceutical preparation, comprises the steps：
(1) sweeting agent is added in appropriate purified water, and solution a is made in stirring, standby；
(2) appropriate purified water is taken, antioxidant, methanesulfonic acid arbidol crystal formation C is sequentially added, is stirred, is made solution b, standby
With；
(3), during be slowly added to the solution a to the solution b, solution c is made in stirring, standby；
(4) pH adjusting agent and appropriate purified water are added in the solution c to adjust the pH value of the solution c to 3-5,
The purified water of aromatic and surplus is then added, is stirred, is made solution d, standby；
(5) the solution d sequentially passes through filter, fill, sterilizing, that is, the pharmaceutical preparation of methanesulfonic acid arbidol is obtained, described
Pharmaceutical preparation is oral solution.
Application of the above-mentioned methanesulfonic acid arbidol pharmaceutical preparation in antiviral drugs are prepared.
The above-mentioned technical proposal of the present invention has the advantage that：
1st, the pharmaceutical preparation of methanesulfonic acid arbidol of the present invention, by adopt one hydration methanesulfonic acid arbidol for
Principal agent, to be up to the advantage of 50～100mg/mL using its dissolubility in 25 DEG C of water, can strengthen methanesulfonic acid arbidol and exist
Dispersibility in aqueous solution, to promote drug absorption, improves the bioavailability of medicine.
2nd, the pharmaceutical preparation of methanesulfonic acid arbidol of the present invention, its hydration methanesulfonic acid arbidol of principal agent one is with crystalline substance
The form of type C is present, and the stability of crystal form is good, it is easy to preserves, meets the requirement of preparation technique.
3rd, the pharmaceutical preparation of methanesulfonic acid arbidol of the present invention, it is contemplated that methanesulfonic acid arbidol is in acid condition
Under stable in properties, but under neutral and alkalescence condition cause arbidol to be analysed because methanesulfonic acid easily reacts with hydroxide ion
Go out, and the phenolic hydroxyl group in methanesulfonic acid arbidol molecule is stable in acid condition, easy oxygen under neutral and alkalescence condition
Change degeneration, thus the pharmaceutical preparation of the present invention passes through to add pH adjusting agent to provide sour environment, control ph is 3-5, while
Antioxidant is added, not only can so be guaranteed that methanesulfonic acid arbidol is readily soluble, not separated out crystal, and also improve the steady of preparation
Qualitative；In addition, methanesulfonic acid arbidol bitter and puckery flavor, by add sweeting agent can with taste masking, while add again appropriate aromatic with
Further improve mouthfeel；Thus pharmaceutical preparation of the invention is by using sweeting agent, aromatic, pH adjusting agent, antioxidant and pure
Change water obtained liquid preparation as adjuvant, as medicine is disperseed in aqueous with molecularity, thus absorbs fast, energy
Rapid performance drug effect, further increases the bioavailability of medicine, and can also improve patient medication compliance, be particularly suitable for
Old man and children taking.
4th, the preparation method of methanesulfonic acid arbidol pharmaceutical preparation of the present invention, by first individually preparing sweeting agent
Into solution a, then it is added into again to being dissolved with the solution b of principal agent, to avoid because molten caused by sweeting agent large usage quantity institute
Solution overlong time further has influence on principal agent property；For avoiding the addition of excipient to the impact of solution ph, the preparation of the present invention
Method adds pH adjusting agent in the rear stage as much as possible, to guarantee that final solution has predetermined pH value.In addition, the system of the present invention
Preparation Method also has process is simple and easily operated.
Description of the drawings
For the technical scheme being illustrated more clearly that in the specific embodiment of the invention, specific embodiment will be retouched below
Needed for stating, accompanying drawing to be used is briefly described, it should be apparent that, drawings in the following description are some realities of the present invention
Mode is applied, for those of ordinary skill in the art, on the premise of not paying creative work, can be with attached according to these
Figure obtains other accompanying drawings.
XRPD collection of illustrative plates of the Fig. 1 for methanesulfonic acid arbidol crystal formation C obtained in the embodiment of the present invention 1；
TG-DSC collection of illustrative plates of the Fig. 2 for methanesulfonic acid arbidol crystal formation C obtained in the embodiment of the present invention 1.
Specific embodiment
Technical scheme is clearly and completely described below in conjunction with accompanying drawing, it is clear that described enforcement
Example is a part of embodiment of the invention, rather than whole embodiments.Embodiment in based on the present invention, ordinary skill
The every other embodiment obtained under the premise of creative work is not made by personnel, belongs to the scope of protection of the invention.
As long as additionally, involved technical characteristic in invention described below different embodiments does not just constitute conflict each other
Can be combined with each other.
Embodiment 1
A kind of preparation technology of methanesulfonic acid arbidol crystal formation C is present embodiments provided, is comprised the steps：
50.0g methanesulfonic acid arbidols, 25.0g pure water and 250.0g acetone is sequentially added in 250mL there-necked flasks, not
Backflow is warming up under disconnected stirring, after solid all dissolves, 0～5 DEG C is cooled to, stirring and crystallizing 2h is filtered, and filter cake is through 50 DEG C of drums
Methanesulfonic acid arbidol crystal formation C is after air-drying dry 4h.After measured, methanesulfonic acid arbidol crystal formation C is molten in 25 DEG C of water
Xie Du is 50～100mg/mL.
Under the testing conditions shown in table 1, methanesulfonic acid arbidol crystal formation C obtained in the present embodiment is radiated using Cu-K α,
Obtain as shown in Figure 1 with 2 θ of the angle of diffraction as abscissa, XRPD collection of illustrative plates of the intensity I as vertical coordinate.In addition, adopting TG-DSC technology
Thermogravimetric-differential scanning calorimetric analysis are carried out to above-mentioned crystal formation C, its TG-DSC collection of illustrative plates is as shown in Fig. 2 the TG curves from Fig. 2 can
To find out, water of crystallization containing a molecule in the molecular structure of crystal formation C obtained in the present embodiment, its content are 3.1wt%, Fig. 2
In DSC curve peak value be 176.2 DEG C place have feature melting absworption peak.
The detection parameter of table 1XRPD
Embodiment 2
The raw material of oral administration solution is consisted of：
The preparation method of oral administration solution comprises the steps：
Sorbitol, sucrose are dissolved in appropriate purified water, are then slowly added into containing methanesulfonic acid arbidol crystal formation
In C, the aqueous solution of disodium edetate, mix, add citric acid and appropriate purified water solution ph is adjusted as 3～5, add
Flavoring orange essence, adds purified water, mixes and be settled to 1000mL, filters, fill, 100 DEG C of sterilizing 30min, obtain final product methanesulfonic acid Ah
Than Dorr oral administration solution.
Evaluate：Sample is colorless clear liquid, micro- sweet, good mouthfeel.
Embodiment 3
The raw material of oral administration solution is consisted of：
Methanesulfonic acid arbidol crystal formation C 2.5g obtained in embodiment 1
The preparation method of oral administration solution comprises the steps：
Mannitol, sucrose are dissolved in appropriate purified water, are then slowly added into containing methanesulfonic acid arbidol crystal formation
In the solution of C, tartaric acid and appropriate purified water, mix the pH value of solution is adjusted as 3～4, add flavoring banana essence, add pure
Change water and be settled to 1000mL, filter, fill, 100 DEG C of sterilizing 30min obtain final product methanesulfonic acid arbidol oral administration solution.
Evaluate：Sample is colorless clear liquid, and the micro- acid of taste is good in taste.
Embodiment 4
The raw material of oral administration solution is consisted of：
The preparation method of oral administration solution comprises the steps：
Xylose, sucralose, steviosin are dissolved in appropriate purified water, are then slowly added into containing methanesulfonic acid Ah ratio
In the solution of Dorr crystal formation C, citric acid and suitable quantity of water, mix the pH value of solution is adjusted as 4～5, add strawberry essence, mend
Plus purified water 1000mL is settled to, and filtering, fill, 100 DEG C of sterilizing 30min obtain final product methanesulfonic acid arbidol oral administration solution.
Evaluate：Sample is colorless clear liquid, and the micro- acid of taste, abnormal smells from the patient perfume are good in taste.
Embodiment 5
The raw material composition of oral administration solution：
The preparation method of oral administration solution comprises the steps：
Sorbitol, aspartame are dissolved in appropriate purified water, are then slowly added into containing methanesulfonic acid arbidol
In crystal formation C, the aqueous solution of disodium edetate, mix, add citric acid and suitable quantity of water the pH value of solution is adjusted as 3.5～4.5,
Peach flavor is added, purified water is added, 1000mL is mixed and be settled to, is filtered, fill, 100 DEG C of sterilizing 30min are obtained final product
Methanesulfonic acid arbidol oral administration solution.
Evaluate：Sample is colorless clear liquid, micro- sweet, good mouthfeel.
Embodiment 6
The raw material composition of oral administration solution：
The preparation method of oral administration solution comprises the steps：
Sucralose, aspartame are dissolved in appropriate purified water, are then slowly added into containing methanesulfonic acid Ah than many
In the solution of your crystal formation C, citric acid and appropriate purified water, mix solution ph is adjusted as 3～4.5, add cherry essence,
Purified water is added, 1000mL is mixed and be settled to, is filtered, fill, 100 DEG C of sterilizing 30min obtain final product methanesulfonic acid arbidol oral
Solution.
Evaluate：Sample is colorless clear liquid, micro- sour-sweet, good in taste.
Embodiment 7
The raw material of oral administration solution is consisted of：
The preparation method of oral administration solution comprises the steps：
Sorbitol, steviosin are dissolved in appropriate purified water, are then slowly added into brilliant containing methanesulfonic acid arbidol
In the solution of type C, tartaric acid and appropriate purified water, mix the pH value of solution is adjusted as 3.5～5, add Mint Essence, mend
Plus purified water, 1000mL being mixed and be settled to, is filtered, fill, 100 DEG C of sterilizing 30min obtain final product methanesulfonic acid arbidol orally molten
Liquid.
Evaluate：Sample is colorless clear liquid, sweeter, fragrance, good mouthfeel.
Embodiment 8
The raw material of oral administration solution is consisted of：
The preparation method of oral administration solution comprises the steps：
Sorbitol, saccharin sodium are dissolved in appropriate purified water, are then slowly added into brilliant containing methanesulfonic acid arbidol
In type C, the aqueous solution of disodium edetate, mix, add citric acid and appropriate purified water the pH value of solution to be adjusted as 3～4, then
Mint Essence is added, purified water is added, is mixed and be settled to 1000mL, filtered, fill, 100 DEG C of sterilizing 30min obtain final product first sulphur
Sour arbidol oral administration solution.
Evaluate：Sample is colorless clear liquid, micro- sweet, refrigerant, good mouthfeel.
Embodiment 9
The raw material of oral administration solution is consisted of：
The preparation method of oral administration solution comprises the steps：
Mannitol, sucrose are dissolved in appropriate purified water, are then slowly added into containing methanesulfonic acid arbidol crystal formation
In C, the aqueous solution of sodium pyrosulfite, mix, add sodium lactate and appropriate purified water the pH value of solution to be adjusted as 4～5, then plus
Enter flavoring banana essence, add purified water, mix and be settled to 1000mL, filter, fill, 100 DEG C of sterilizing 30min obtain final product methanesulfonic acid
Arbidol oral administration solution.
Evaluate：Sample is colorless clear liquid, sweet, fragrance, good mouthfeel.
Experimental example
Influence factor's stability test is carried out to methanesulfonic acid arbidol oral administration solution obtained in the embodiment of the present invention 7, is had
Body examination method for testing is：
Take the methanesulfonic acid arbidol oral administration solution in right amount, accelerated test condition (75% ± 5%RH, 40 DEG C ± 2
DEG C), place under exposure experiments to light condition (4500lx ± 500lx), carry out relevant material detection in 5 days, 10 days, result (be shown in Table
2) compared with 0 day.
The stability of 2 methanesulfonic acid arbidol oral administration solution of table
As shown in Table 2, methanesulfonic acid arbidol oral administration solution obtained in embodiment 7 accelerated test (75% ± 5%RH,
40 DEG C ± 2 DEG C), result shows under the conditions of exposure experiments to light (4500lx ± 500lx)：Impurity does not have significant change within 5 days, 10 days impurity
It is increased slightly, illustrates that methanesulfonic acid arbidol oral administration solution of the present invention has preferable stability, its storage condition should
Lucifuge, it is to avoid high temperature.
Obviously, above-described embodiment is only intended to clearly illustrate example, and the not restriction to embodiment.Right
For those of ordinary skill in the art, can also make on the basis of the above description other multi-forms change or
Change.There is no need to be exhaustive to all of embodiment.And thus extended obvious change or
Change among still in the protection domain of the invention.
Claims (10)
1. a kind of pharmaceutical preparation of methanesulfonic acid arbidol, methanesulfonic acid arbidol and medicine of the pharmaceutical preparation by effective dose
Acceptable excipient composition on, it is characterised in that
Shown in the structure such as formula (I) of the methanesulfonic acid arbidol：
2. the pharmaceutical preparation of methanesulfonic acid arbidol according to claim 1, it is characterised in that the methanesulfonic acid Ah is than more
The XRPD collection of illustrative plates that your crystal formation C is represented with the 2 θ ± 0.2 ° angles of diffraction 6.183 °, 7.858 °, 18.290 °, 18.566 °,
Feature is shown at 21.465 °, 21.717 °, 23.934 °, 24.633 °, 25.011 °, 25.617 °, 26.013 ° and 31.382 °
Diffraction maximum.
3. the pharmaceutical preparation of methanesulfonic acid arbidol according to claim 1 and 2, it is characterised in that methanesulfonic acid Ah
XRPD collection of illustrative plates than the crystal formation C of Dorr has following characteristic diffraction peak：
4. the pharmaceutical preparation of the methanesulfonic acid arbidol according to any one of claim 1-3, it is characterised in that the first sulphur
The DSC collection of illustrative plates of the crystal formation C of sour arbidol is that there is at 176.2 DEG C feature to melt absworption peak in peak value.
5. the pharmaceutical preparation of the methanesulfonic acid arbidol according to any one of claim 1-4, it is characterised in that the medicine
Preparation is liquid preparation, and the liquid preparation is oral solution, syrup, mixture, Emulsion or injection.
6. the pharmaceutical preparation of methanesulfonic acid arbidol according to claim 5, it is characterised in that the excipient includes pure
One or more in change water and sweeting agent, aromatic, pH adjusting agent or antioxidant.
7. the pharmaceutical preparation of methanesulfonic acid arbidol according to claim 6, it is characterised in that the institute of every 1000 parts by volume
State oral solution to be made up of the following raw material：
Wherein, weight portion is g/mL with the relation of parts by volume.
8. the pharmaceutical preparation of the methanesulfonic acid arbidol according to claim 6 or 7, it is characterised in that
The sweeting agent includes sucrose, Fructose, Sorbitol, Mannitol, xylitol, sucralose, aspartame, steviosin or sugar
One or more in smart sodium；
The aromatic is included in strawberry essence, cherry essence, flavoring banana essence, peach flavor, flavoring orange essence or Mint Essence
One or more；
The pH adjusting agent includes citric acid, sodium citrate, lactic acid, sodium lactate, citric acid, sodium citrate, tartaric acid or winestone
One or more in sour sodium；
The antioxidant includes one kind in disodium edetate, sodium pyrosulfite, sodium sulfite, tartaric acid or citric acid or many
Kind.
9. a kind of method of the methanesulfonic acid arbidol pharmaceutical preparation prepared described in any one of claim 6-8, it is characterised in that
Comprise the steps：
(1) sweeting agent is added in appropriate purified water, and solution a is made in stirring, standby；
(2) appropriate purified water is taken, antioxidant, methanesulfonic acid arbidol crystal formation C is sequentially added, is stirred, is made solution b, standby；
(3), during be slowly added to the solution a to the solution b, solution c is made in stirring, standby；
(4) pH adjusting agent and appropriate purified water are added to adjust the pH value of the solution c to 3-5 in the solution c, then
The purified water of aromatic and surplus is added, is stirred, is made solution d, standby；
(5) the solution d sequentially passes through filter, fill, sterilizing, that is, the pharmaceutical preparation of methanesulfonic acid arbidol, the medicine is obtained
Preparation is oral solution.
10. application of the methanesulfonic acid arbidol pharmaceutical preparation described in any one of claim 1-8 in antiviral drugs are prepared.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610763671.2A CN106491598A (en) | 2016-08-30 | 2016-08-30 | A kind of pharmaceutical preparation of methanesulfonic acid arbidol and preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610763671.2A CN106491598A (en) | 2016-08-30 | 2016-08-30 | A kind of pharmaceutical preparation of methanesulfonic acid arbidol and preparation method and application |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106491598A true CN106491598A (en) | 2017-03-15 |
Family
ID=58290009
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610763671.2A Pending CN106491598A (en) | 2016-08-30 | 2016-08-30 | A kind of pharmaceutical preparation of methanesulfonic acid arbidol and preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106491598A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112206225A (en) * | 2020-07-16 | 2021-01-12 | 郑鉴忠 | Production method of anti-new coronavirus western medicine with monarch, minister, assistant and guide compatibility |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005102320A1 (en) * | 2004-04-21 | 2005-11-03 | Zakrytoe Aktsionernoe Obschestvo 'masterklon' | Medicinal agent for treating viral infections |
| CN1792362A (en) * | 2005-11-29 | 2006-06-28 | 沈阳中海生物技术开发有限公司 | Abiduoer and its salts prepns. for vena administration, and its preparing method |
| CN104529833A (en) * | 2014-12-10 | 2015-04-22 | 广东东阳光药业有限公司 | Substituted cyclobutane carboxylic acid compounds and application thereof |
-
2016
- 2016-08-30 CN CN201610763671.2A patent/CN106491598A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005102320A1 (en) * | 2004-04-21 | 2005-11-03 | Zakrytoe Aktsionernoe Obschestvo 'masterklon' | Medicinal agent for treating viral infections |
| CN1792362A (en) * | 2005-11-29 | 2006-06-28 | 沈阳中海生物技术开发有限公司 | Abiduoer and its salts prepns. for vena administration, and its preparing method |
| CN104529833A (en) * | 2014-12-10 | 2015-04-22 | 广东东阳光药业有限公司 | Substituted cyclobutane carboxylic acid compounds and application thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112206225A (en) * | 2020-07-16 | 2021-01-12 | 郑鉴忠 | Production method of anti-new coronavirus western medicine with monarch, minister, assistant and guide compatibility |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20050069585A1 (en) | Diphenhydramine tannate liquid and semi-solid compositions and methods of use | |
| US10201519B2 (en) | Stabilized pediatric suspension of carisbamate | |
| KR101779214B1 (en) | Liquid formulations of salts of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine | |
| JP2004522802A (en) | Water-soluble and savory complex | |
| US9801876B2 (en) | Complex granule formulation having improved stability comprising levocetirizine and montelukast | |
| CN112220748B (en) | Desloratadine oral liquid preparation and preparation method thereof | |
| US20200206223A1 (en) | Liquid dosage forms of imatinib | |
| CN106491598A (en) | A kind of pharmaceutical preparation of methanesulfonic acid arbidol and preparation method and application | |
| RU2288218C2 (en) | Gatifloxacin formulations for using in pediatrics | |
| US20220218606A1 (en) | Ready to use diclofenac stick packs | |
| CN104306331A (en) | Cetirizine hydrochloride syrup | |
| RU2515557C9 (en) | Pharmaceutical salt of 8-methyl-7-[5-methyl-6-(methylamino)-3-pyridinyl]-1-cyclopropyl-4-oxo-1,4-dihydro-3-quinoline carboxylic acid, pharmaceutical composition containing same, medicinal agent and method of treating or preventing bacterial infections using said salts | |
| HRP20000530A2 (en) | Pharmaceutical compositions | |
| CN101288645A (en) | Tilidine medicine resin oral turbid suspension and preparation method thereof | |
| CN114028339A (en) | Rivastigmine bitartrate-PLGA long-acting slow-release microsphere for injection and process | |
| AU666678B2 (en) | Trimethoprim oral liquid | |
| CN113784711A (en) | Orally disintegrating tablet comprising glycopyrronium bromide and method for increasing bioavailability | |
| WO2013062497A1 (en) | Liquid pharmaceutical formulations | |
| US20230233494A1 (en) | Bioavailable sugar-based diclofenac formulations | |
| CN116172948A (en) | Cetirizine hydrochloride oral solution and preparation method thereof | |
| WO2022247609A1 (en) | Tizanidine liquid preparation and use thereof | |
| WO2018002738A1 (en) | Taste masked liquid pharmaceutical composition of (rs)-4-(ethyl[1-(4-methoxyphenyl)propan-2-yl]amino)butyl 3,4-dimethoxybenzoate or pharmaceutically acceptable salts thereof | |
| CN115025080A (en) | Anti-influenza virus pharmaceutical composition and application thereof | |
| BRPI0716002A2 (en) | Inclusion complex, process of preparation of an inclusion complex and composition of treatment and prevention of hypochondria and obesity |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170315 |