CN106176582A - A kind of for atenolol emulsifiable paste treating infant hemangioma and preparation method thereof - Google Patents
A kind of for atenolol emulsifiable paste treating infant hemangioma and preparation method thereof Download PDFInfo
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- CN106176582A CN106176582A CN201610719210.5A CN201610719210A CN106176582A CN 106176582 A CN106176582 A CN 106176582A CN 201610719210 A CN201610719210 A CN 201610719210A CN 106176582 A CN106176582 A CN 106176582A
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- Prior art keywords
- atenolol
- parts
- emulsifiable paste
- water
- octadecanol
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Classifications
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- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- 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
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- 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
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- 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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
Abstract
The invention belongs to field of medicine preparing technology, it particularly relates to a kind of for atenolol emulsifiable paste treating infant hemangioma and preparation method thereof.A kind of atenolol emulsifiable paste for treating infant hemangioma of the present invention, includes that based on quality is divided atenolol 1.0 5.0 parts, stearic acid 5.0 10, octadecanol 3.0 7.5 parts, 0.5 2.0 parts of vaseline, glyceryl monostearate 4.5 6.0 parts, PLURONICS F87 1.0 4.0 parts, ethyl hydroxybenzoate 0.1 0.2 parts, glycerol 6.0 10 parts, surplus are water.Compared with prior art, the atenolol emulsifiable paste for treating infant hemangioma of the present invention, there is preferable curative effect, easy to use and side effect is little.
Description
Technical field
The invention belongs to field of medicine preparing technology, it particularly relates to a kind of for treat infant hemangioma Ah
For Luo Er emulsifiable paste and preparation method thereof.
Background technology
Infant hemangioma (infant hemangiomas, IH) is congenital benign tumor or vascular malformation, common
When baby due or after birth soon, it originates from the embryo angioblast of remnants.The hazardness of infant hemangioma
Various, majority can affect body function or destroy appearance, and minority giant hemangioma may result in abnormal hemodynamics even mental and physical efforts
Exhaustion etc. and threat to life.
Atenolol is selectivity β 1 receptor blocking agent, is slightly soluble in water, chloroform, is dissolved in ethanol, is practically insoluble in ether,
It is difficult to through blood brain barrier or produces β 2 effect, infant hemangioma is had obvious therapeutical effect.Atenolol is existing
Administering mode is predominantly administered orally or nasal-cavity administration, can play drug effect through being absorbed into blood circulation.But, existing infant blood vessel
Tumor (IH) is most commonly seen on skin, while medicine is transported to site of action onset after absorbing, and also can be at infant
Other organs is accumulated, and has side effects, and needed for drug effect, the consumption of medicine is the biggest in addition.
For shallow infant hemangioma, topical drug level is high and systemic Absorption reduces, easy to use, can
Preferable curative effect and side effect can be had little, have a extensive future.
Present invention firstly provides and prepare atenolol emulsifiable paste for treating infant hemangioma, although existing atenolol is controlled
Treat the research of infant hemangioma, but its research is entirely absorbed into onset after systemic blood circulation；Infant hemangioma is controlled
The treatment cycle is long, and it is relatively big that long term systemic heavy dose is administered side effect, therefore, uses atenolol emulsifiable paste to be used locally for infant blood vessel
Tumor treatment is preferably to select.
Summary of the invention
For solving above-mentioned technical problem, the invention provides a kind of atenolol emulsifiable paste for treating infant hemangioma
And preparation method thereof.
The present invention provides a kind of atenolol emulsifiable paste for treating infant hemangioma, includes Ah replacing Lip river based on quality is divided
You are 1.0-5.0 part, stearic acid 5.0-10, octadecanol 3.0-7.5 part, vaseline 0.5-2.0 part, glyceryl monostearate 4.5-
6.0 parts, PLURONICS F87 1.0-4.0 part, ethyl hydroxybenzoate 0.1-0.2 part, glycerol 6.0-10 part, surplus be water.
The present invention provides a kind of atenolol emulsifiable paste for treating infant hemangioma, includes Ah replacing Lip river based on quality is divided
You are 1.0-3.0 part, stearic acid 6.0-10 part, octadecanol 3.0-6.0 part, vaseline 0.5-1.5 part, glyceryl monostearate 4.5-
5.3 parts, PLURONICS F87 1.0-3.0 part, ethyl hydroxybenzoate 0.1-0.16 part, glycerol 6.0-9.0 part, surplus be water.
The present invention provides a kind of atenolol emulsifiable paste for treating infant hemangioma, includes Ah replacing Lip river based on quality is divided
That 1.5 parts, stearic acid 7.5 parts, octadecanol 4.5 parts, 1.0 parts of vaseline, glyceryl monostearate 5.0 parts, PLURONICS F87
2.6 parts, ethyl hydroxybenzoate 0.15 part, glycerol 8.0 parts, surplus be water.
The present invention provides a kind of atenolol cream preparation method for treating infant hemangioma, comprises the following steps:
1) stearic acid, octadecanol, vaseline, glyceryl monostearate are placed in container, are heated to melting mixing, water-soluble control
Temperature processed, at 65-75 DEG C, obtains oil phase；
2) being mixed with ethyl hydroxybenzoate by part water boil, stirring, to being completely dissolved, adds residue water, adds PLURONICS F87,
After to be dissolved, add atenolol, to be dissolved after, add glycerol mixing, temperature controlled water baths, at 65-75 DEG C, obtains aqueous phase；
3) under insulated and stirred, oil phase is slowly added in aqueous phase, stirring and emulsifying 5 minutes, is cooled to room temperature and i.e. obtains atenolol
Emulsifiable paste.
Compared with prior art, the atenolol emulsifiable paste for treating infant hemangioma of the present invention, have preferably
Curative effect, easy to use and side effect is little.
Detailed description of the invention
Below in conjunction with specific embodiment to the atenolol emulsifiable paste for treating infant hemangioma of the present invention
It is described further, but protection scope of the present invention is not limited to this.
Embodiment 1
Prescription: atenolol 1.0%, stearic acid 10%, octadecanol 3.0%, vaseline 2.0%, glyceryl monostearate 6.0%, pool Lip river
Husky nurse 188 1.0%, ethyl hydroxybenzoate 0.1%, glycerol 6.0%, surplus are water.
Preparation method: first, is placed in stearic acid, octadecanol, vaseline, glyceryl monostearate in container, is heated to
Melting mixing, water-soluble control temperature, at 65 DEG C, obtains oil phase；Secondly, being mixed with ethyl hydroxybenzoate by part water boil, stirring is to complete
CL, add residue water, add PLURONICS F87, to be dissolved after, add atenolol, to be dissolved after, add glycerol mix
Closing, temperature controlled water baths, at 65 DEG C, obtains aqueous phase；Finally, under insulated and stirred, oil phase is slowly added in aqueous phase, stirring and emulsifying
5 minutes, it is cooled to room temperature and i.e. obtains atenolol emulsifiable paste.
Embodiment 2
Prescription: atenolol 5.0%, stearic acid 5.0%, octadecanol 7.5%, vaseline 0.5%, glyceryl monostearate 4.5%, pool
Luo Shamu 188 4.0%, ethyl hydroxybenzoate 0.2%, glycerol 10%, surplus are water.
Preparation method: first, is placed in stearic acid, octadecanol, vaseline, glyceryl monostearate in container, is heated to
Melting mixing, water-soluble control temperature, at 70 DEG C, obtains oil phase；Secondly, being mixed with ethyl hydroxybenzoate by part water boil, stirring is to complete
CL, add residue water, add PLURONICS F87, to be dissolved after, add atenolol, to be dissolved after, add glycerol mix
Closing, temperature controlled water baths, at 70 DEG C, obtains aqueous phase；Finally, under insulated and stirred, oil phase is slowly added in aqueous phase, stirring and emulsifying
4 minutes, it is cooled to room temperature and i.e. obtains atenolol emulsifiable paste.
The present invention provides a kind of atenolol emulsifiable paste for treating infant hemangioma, includes Ah replacing Lip river based on quality is divided
That 1.0%-5.0%, stearic acid 5.0%-10%, octadecanol 3.0%-7.5%, vaseline 0.5%-2.0%, glyceryl monostearate
4.5%-6.0%, PLURONICS F87 1.0%-4.0%, ethyl hydroxybenzoate 0.1%-0.2%, glycerol 6.0%-10%, surplus are water.
Embodiment 3
Prescription: atenolol 3.0%, stearic acid 6.0%, octadecanol 6.0%, vaseline 1.5%, glyceryl monostearate 5.3%, pool
Luo Shamu 188 3.0%, ethyl hydroxybenzoate 0.16%, glycerol 9.0%, surplus are water.
Preparation method: first, is placed in stearic acid, octadecanol, vaseline, glyceryl monostearate in container, is heated to
Melting mixing, water-soluble control temperature, at 75 DEG C, obtains oil phase；Secondly, being mixed with ethyl hydroxybenzoate by part water boil, stirring is to complete
CL, add residue water, add PLURONICS F87, to be dissolved after, add atenolol, to be dissolved after, add glycerol mix
Closing, temperature controlled water baths, at 75 DEG C, obtains aqueous phase；Finally, under insulated and stirred, oil phase is slowly added in aqueous phase, stirring and emulsifying
6 minutes, it is cooled to room temperature and i.e. obtains atenolol emulsifiable paste.
Embodiment 4
Prescription: atenolol 1.5%, stearic acid 7.5%, octadecanol 4.5%, vaseline 1.0%, glyceryl monostearate 5.0%, pool
Luo Shamu 188 2.6%, ethyl hydroxybenzoate 0.15%, glycerol 8.0%, surplus are water.
Preparation method: first, is placed in stearic acid, octadecanol, vaseline, glyceryl monostearate in container, is heated to
Melting mixing, water-soluble control temperature, at 72 DEG C, obtains oil phase；Secondly, being mixed with ethyl hydroxybenzoate by part water boil, stirring is to complete
CL, add residue water, add PLURONICS F87, to be dissolved after, add atenolol, to be dissolved after, add glycerol mix
Closing, temperature controlled water baths, at 72 DEG C, obtains aqueous phase；Finally, under insulated and stirred, oil phase is slowly added in aqueous phase, stirring and emulsifying
5 minutes, it is cooled to room temperature and i.e. obtains atenolol emulsifiable paste.
Embodiment 5
Prescription: atenolol 1.0%, stearic acid 10%, octadecanol 3.0%, vaseline 2.0%, glyceryl monostearate 6.0%, pool Lip river
Husky nurse 188 1.0%, ethyl hydroxybenzoate 0.1%, glycerol 6.0%, Rhizoma Corydalis phenanthrene alkali A 0.2%, surplus are water.
Preparation method: first, is placed in stearic acid, octadecanol, vaseline, glyceryl monostearate in container, is heated to
Melting mixing, water-soluble control temperature, at 65 DEG C, obtains oil phase；Secondly, being mixed with ethyl hydroxybenzoate by part water boil, stirring is to complete
CL, adds residue water, adds PLURONICS F87, to be dissolved after, add atenolol and Rhizoma Corydalis phenanthrene alkali A(1-[2-(N-
Ammonium methyl ethyl)]-3,4,6,7-tetramethoxies are luxuriant and rich with fragrance), to be dissolved after, add glycerol mixing, temperature controlled water baths at 65 DEG C,
Aqueous phase；Finally, under insulated and stirred, oil phase is slowly added in aqueous phase, stirring and emulsifying 5 minutes, is cooled to room temperature and i.e. obtains Ah replacing
Luo Er emulsifiable paste.
Comparative example 1
Prescription: stearic acid 7.5%, octadecanol 4.5%, vaseline 1.0%, glyceryl monostearate 5.0%, PLURONICS F87
2.6%, ethyl hydroxybenzoate 0.15%, glycerol 8.0%, surplus are water.
Preparation method: first, is placed in stearic acid, octadecanol, vaseline, glyceryl monostearate in container, is heated to
Melting mixing, water-soluble control temperature, at 71 DEG C, obtains oil phase；Secondly, being mixed with ethyl hydroxybenzoate by part water boil, stirring is to complete
CL, add residue water, add PLURONICS F87, to be dissolved after, add glycerol mixing, temperature controlled water baths at 71 DEG C,
Obtain aqueous phase；Finally, under insulated and stirred, oil phase is slowly added in aqueous phase, stirring and emulsifying 5 minutes, is cooled to room temperature and i.e. has leisure
Virgin's milk cream.
Stability experiment
Study on the stability method is: 1) centrefuge experiment: emulsifiable paste loads centrifuge tube, 3000r min-1, centrifugal 30min, sees
Examine the profit layering result of emulsifiable paste；2) cold-resistant experiment: at temperature is-15 DEG C, emulsifiable paste is placed 24 hours, observe emulsifiable paste
Profit layering result；3) heat-resistant experiment: be placed in by emulsifiable paste in 55 DEG C of calorstats 6 hours, observes the profit layering result of emulsifiable paste；Adopt
In aforementioned manners the atenolol emulsifiable paste of all embodiments is carried out stability experiment.The performance test results is shown in as follows:
| Project | Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | Embodiment 5 |
| Centrefuge experiment | Breast grain size is uniform, has no layering | Breast grain size is uniform, has no layering | Breast grain size is uniform, has no layering | Breast grain size is uniform, has no layering | Breast grain size is uniform, has no layering |
| Cold-resistant experiment | Breast grain size is uniform, has no layering | Breast grain size is uniform, has no layering | Breast grain size is uniform, has no layering | Breast grain size is uniform, has no layering | Breast grain size is uniform, has no layering |
| Heat-resistant experiment | Breast grain size is uniform, has no layering | Breast grain size is uniform, has no layering | Breast grain size is uniform, has no layering | Breast grain size is uniform, has no layering | Breast grain size is uniform, has no layering |
From result, the stability of emulsifiable paste of the present invention is preferable, and the profit of emulsifiable paste is not stratified, and emulsifiable paste can resist cold, heat-resisting.
Effect experiment
Ointment external prepared by embodiment 1, embodiment 2, embodiment 3, embodiment 4, embodiment 5, comparative example 1, positive
Comparison medicine is administered orally, by visual analogue scales (Visual Analogue Scale/Score, be called for short VAS) scoring and
DeltaHAS value is investigated and is treated angiomatous curative effect, and VAS marks 0 point and represents that tumor body is not any change, and 100 are divided into tumor body to disappear completely
Losing ,-100 are divided into swollen 1 times stayed before rising to treatment；Hemangioma activity score (the Hemangioma Activity
Score, HAS), the active situation for hemangioma growth is estimated, and scoring score value is the highest, represents hemangioma growth the most alive
Jump.According to the tumor body photo grading before and after treatment, HAS can be drawnT0And HASTlValue, by both difference DeltaHAS values
(DeltaHAS=HAST0-HASTl) representing the change of tumor bulk-growth situation, before and after the biggest explanation treatment of DeltaHAS value, difference is greatly,
Treatment good effect.
Result is as follows:
| Inspection target | Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | Embodiment 5 | Comparative example 1 | Positive control drug |
| VAS marks | 67.5±13.4 | 68.2±15.3 | 73.6±14.1 | 73.8±13.3 | 77.8±15.3 | -30.8±26.6 | 72.2±14.6 |
| DeltaHAS value | 4.25±0.5 | 4.75±0.25 | 4.5±0.68 | 4.78±0.65 | 4.88±0.65 | 2.15±0.2 | 4.73±0.35 |
From investigate result, comparative example 1 prepare ointment external to hemangioma without obvious therapeutic action, external embodiment
1, embodiment 2, embodiment 3, embodiment 4, the atenolol emulsifiable paste of embodiment 5 preparation and oral propranolol positive control drug pair
Hemangioma all has obvious therapeutical effect.But the oral medicinal dosage of positive control is bigger, atenolol emulsifiable paste is used not only have relatively
Good curative effect, easy to use and dosage is little, and side effect is little.
Claims (4)
1. the atenolol emulsifiable paste being used for treating infant hemangioma, it is characterised in that include atenolol based on quality is divided
1.0-5.0 part, stearic acid 5.0-10, octadecanol 3.0-7.5 part, vaseline 0.5-2.0 part, glyceryl monostearate 4.5-6.0
Part, PLURONICS F87 1.0-4.0 part, ethyl hydroxybenzoate 0.1-0.2 part, glycerol 6.0-10 part, surplus are water.
Atenolol emulsifiable paste the most according to claim 1, it is characterised in that include atenolol 1.0-3.0 based on quality is divided
Part, stearic acid 6.0-10 part, octadecanol 3.0-6.0 part, vaseline 0.5-1.5 part, glyceryl monostearate 4.5-5.3 part, pool
Luo Shamu 188 1.0-3.0 part, ethyl hydroxybenzoate 0.1-0.16 part, glycerol 6.0-9.0 part, surplus are water.
Atenolol emulsifiable paste the most according to claim 1, it is characterised in that include based on quality is divided atenolol 1.5 parts,
Stearic acid 7.5 parts, octadecanol 4.5 parts, 1.0 parts of vaseline, glyceryl monostearate 5.0 parts, PLURONICS F87 2.6 parts, Buddhist nun
Pool gold ethyl ester 0.15 part, glycerol 8.0 parts, surplus are water.
4. according to the atenolol emulsifiable paste according to any one of claim 1 ~ 3, it is characterised in that preparation method
Comprise the following steps: 1) stearic acid, octadecanol, vaseline, glyceryl monostearate are placed in container, it is heated to melting
Melting mixing, water-soluble control temperature, at 65-75 DEG C, obtains oil phase；2) being mixed with ethyl hydroxybenzoate by part water boil, stirring is to complete
CL, add residue water, add PLURONICS F87, to be dissolved after, add atenolol, to be dissolved after, add glycerol mix
Closing, temperature controlled water baths, at 65-75 DEG C, obtains aqueous phase；3) under insulated and stirred, oil phase is slowly added in aqueous phase, stirring breast
Change 5 minutes, be cooled to room temperature and i.e. obtain atenolol emulsifiable paste.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610719210.5A CN106176582A (en) | 2016-08-25 | 2016-08-25 | A kind of for atenolol emulsifiable paste treating infant hemangioma and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610719210.5A CN106176582A (en) | 2016-08-25 | 2016-08-25 | A kind of for atenolol emulsifiable paste treating infant hemangioma and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108299279A (en) * | 2018-02-09 | 2018-07-20 | 北京梅尔森医药技术开发有限公司 | Substituted aryl amine alcohol compound and its preparation method and application |
| CN113274348A (en) * | 2021-06-11 | 2021-08-20 | 四川大学华西医院 | Atenolol gel for treating infantile hemangioma, preparation method and application |
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| US20130131181A1 (en) * | 2007-10-19 | 2013-05-23 | Universite Victor Segalen - Bordeaux 2 | Use of a beta blocker for the manufacture of a medicament for the treatment of hemangiomas |
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| US20130131181A1 (en) * | 2007-10-19 | 2013-05-23 | Universite Victor Segalen - Bordeaux 2 | Use of a beta blocker for the manufacture of a medicament for the treatment of hemangiomas |
| CN103054793A (en) * | 2013-01-05 | 2013-04-24 | 广州军区广州总医院 | Propranolol hydrochloride cream used for treating infantile hemangioma, and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108299279A (en) * | 2018-02-09 | 2018-07-20 | 北京梅尔森医药技术开发有限公司 | Substituted aryl amine alcohol compound and its preparation method and application |
| CN113274348A (en) * | 2021-06-11 | 2021-08-20 | 四川大学华西医院 | Atenolol gel for treating infantile hemangioma, preparation method and application |
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