Patents : Therapy & Synthesis
Simple, cheap rapid solution to the
pandemic – Video -- Dr. Richard Bartlett -- ACWT
More than 25 million people live in Taiwan, 25 million people
practically stacked on top of each other. If they practiced social
distancing they’d be out in the ocean floating around. There’s not
enough room for them to do social distancing.
But guess how many people have died to date of the pandemic in
Seven! Only seven!
Only seven! (Yes, I confirmed this on worldometers.com. As of
today, August 5, the number is only seven.)
Texas physician Dr. Richard Bartlett has had a 100 percent success
rate with his patients, many with life-threatening co-morditities,
but the media has been ignoring it.
In this video, Dr. Bartlett shares the stories people who he has
treated using a steroid called budesonide, inhaled through a
nebulizer. Dr. Bartlett has previously referred to his treatment
as a “silver bullet” for the coronavirus. Worth watching at least
the first 5 minutes.
Budesonide: That’s bu as in blue, des as in dess, o as in
oh, nide as in hide) – Budesonide
Only seven deaths of Covid-19 in Taiwan!
“Same situation in Japan,” says Dr Bartlett. “One hundred and
twenty-one million people in Japan, and they’ve had less than a
thousand people die during the whole pandemic. In Singapore, only
12 people have died in the entire country during the whole
What is the secret to these low death counts?
People in those countries are using an inhaled steroid called
budesomide, says Dr Bartlett, who calls budesomide the “silver
“It’s super cheap,” say Dr. Bartlett. “It’s about $200 for the
entire treatment if you use cash. Many of my patients who use
insurance pay nothing out of pocket.”
Budesonide is an asthma medicine, says Dr Bartlett. It’s a
respiratory anti-inflammatory, and Covid-19 is a respiratory
“And it works,” says Dr Bartlett. “A hundred percent of my
(Covid-19) patients are alive.”You use a nebulizer machine.
“People start feeling better after the first treatment,” Bartlett
Note: This was first posted on YouTube more than a month ago. But
have you seen any word about this in the mainstream media?
Every person in the entire world should be made aware of this
simple, cheap rapid solution to the pandemic. They should know
about Dr Bartlett’s “silver bullet.”
Please help spread the word
Budesonide/formoterol, sold under the brand name Symbicort among
others, is a combination medication used in the management of
asthma or chronic obstructive pulmonary disease (COPD). It
contains budesonide, a steroid and formoterol, a long-acting
β2-agonist (LABA). The product monograph does not support its
use for sudden worsening or treatment of active bronchospasm.
However, a 2020 review of the literature does support such use.
It is used by breathing in the medication.
Common side effects include throat pain, influenza, runny nose,
and a yeast infection of the mouth. There were concerns that
the LABA component increases the risk of death in children with
asthma, however these concerns were removed in 2017. Therefore,
this combination is only recommended in those who are not
controlled on an inhaled steroid alone. There is tentative
evidence that typical doses of inhaled steroids and LABAs are safe
in pregnancy. Both formoterol and budesonide are excreted in
Budesonide/formoterol was approved for medical use in the United
States in 2006. It is on the World Health Organization's
List of Essential Medicines, the safest and most effective
medicines needed in a health system. In the United States, as
of 2017, the wholesale cost of an inhaler is about US$30. In
the United Kingdom, the cost as of 2015, was about GB£35 for a
unit with 120 doses. In 2017, it was the 74th most commonly
prescribed medication in the United States, with more than ten
Budesonide/formoterol has shown efficacy to prevent asthma
attacks. It is unclear if budesonide/formoterol differs from
fluticasone and salmeterol in chronic asthma.
The combination is approved in the United States only as a
maintenance medication in asthma and chronic obstructive pulmonary
disease (COPD). However, a 2020 review of the literature does
support use as needed during acute worsening in those with mild
disease, and as maintenance followed by extra doses during
Use for both maintenance and as needed treatment is also known as
single maintenance and reliever therapy ( SMART) and is a
well-established treatment. It has been shown to reduce
asthma exacerbations that require oral corticosteroids, hospital
visits better than maintenance inhaled corticosteroids alone at a
higher dose, or inhaled corticosteroid at the same or higher dose
with a long acting bronchodilator (LABA)), with a short-acting
bronchodilator (SABA) as a reliever. More studies using
budesonide/formoterol SMART in children are needed.
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Common (up to 1 in 10 people)
Mild throat irritation
Oral candidiasis (thrush. significantly less
likely if the patient rinses their mouth out with water after
Often mild, and usually disappear as the medication continues to
Uncommon (up to 1 in 100 people)
Feeling restlessness, nervous, or agitated
Tachycardia (fast heart rate)
Bruising of the skin
Rare (up to 1 in 1,000 people)
Bronchospasm (tightening of the muscles in the
airways causing wheezing immediately after use of the medication,
which is possibly sign of an allergic reaction and should be met
with immediate medical attention)
Hypokalemia (low levels of potassium in the
Very rare (up to 1 in 10,000 people)
Changes in behaviour, especially in children
Chest pain or tightness in chest
Increase in blood glucose levels
Taste changes, such as an unpleasant taste in
Changes in blood pressure
With high doses for a long period of time.
Reduced bone mineral density, causing
Slowed rate of growth in children and
Dysfunction of the adrenal gland, which affects
the production of various hormones
Angioedema (swelling of the face, mouth,
tongue, and/or throat. Difficulty swallowing. Hives. Difficulty
breathing. Feeling of faintness)
Bronchospasm (sudden acute wheezing or
shortness of breath immediately after use of medication. The
patient should use their reliever medication immediately.)
Society and culture
Symbicort in the United States is a metered-dose inhaler and is
available in 160/4.5mcg and 80/4.5mcg per actuation.
In the European Union, Australia, Canada, Israel, Saudi Arabia and
elsewhere the combination is available as a dry powder inhaler in
the following doses: 50/3 (40/2.25), 100/3 (80/2.25), 100/6
(80/4.5), 200/6 (160/4.5) and 400/12 (320/9), where the larger
number is the dose per actuation of budesonide (in micrograms) and
the lower number the dose of formoterol (also in
micrograms).[medical citation needed]
Budesonide/formoterol formulation was introduced in Sweden in
2000. It was approved for use in the United States in July
2006. It is now[when?] approved for use in at least 70
countries, yielding global sales in excess of $1 billion in 2005,
and now[when?] approximately $3.7 billion per annum.[citation
Budesonide/formoterol was approved for use in the European Union
in April 2014.
There are several patents related to the drug; some of them are
already expired. It was initially marketed by AstraZeneca.
"Budesonide / formoterol (Symbicort) Use During Pregnancy".
Drugs.com. 28 August 2019. Retrieved 13 April 2020.
"Symbicort- budesonide and formoterol fumarate dihydrate aerosol".
DailyMed. 24 July 2019. Retrieved 29 April 2020.
"Symbicort Turbohaler 200/6 Inhalation powder - Summary of Product
Characteristics (SmPC)". (emc). 30 August 2019. Retrieved 13 April
Jenkins, CR; Bateman, ED; Sears, MR; O'Byrne, PM (31 March 2020).
"What have we learnt about asthma control from trials of
budesonide/formoterol as maintenance and reliever?". Respirology
(Carlton, Vic.). doi:10.1111/resp.13804. PMID 32237004.
"Safety Alerts for Human Medical Products - Long-Acting Beta
agonists (LABAs) and Inhaled Corticosteroids (ICS): Drug Safety
Communication - Boxed Warning About Asthma-Related Death Removed".
FDA. Retrieved 23 December 2017.
"Global Strategy for Asthma Management and Prevention" (PDF).
Ginasthma.org. 2020. p. 90. Retrieved 9 May 2020. "evidence for
safety of usual doses of ICS and LABA"
"Drug Approval Package: Symbicort (budesonide/formoterol fumarate
dihydrate) NDA #021929". U.S. Food and Drug Administration (FDA).
30 October 2008. Retrieved 29 April 2020.
World Health Organization (2019). World Health Organization model
list of essential medicines: 21st list 2019. Geneva: World Health
Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License:
CC BY-NC-SA 3.0 IGO.
"NADAC as of 2017-12-13". Centers for Medicare and Medicaid
Services. Retrieved 13 December 2017.
British national formulary : BNF 69 (69 ed.). British Medical
Association. 2015. p. 202. ISBN 9780857111562.
"The Top 300 of 2020". ClinCalc. Retrieved 11 April 2020.
"Budesonide; Formoterol - Drug Usage Statistics". ClinCalc.
Retrieved 11 April 2020.
Lasserson, Toby J; Ferrara, Giovanni; Casali, Lucio (7 December
2011). Cochrane Airways Group (ed.). "Combination fluticasone and
salmeterol versus fixed dose combination budesonide and formoterol
for chronic asthma in adults and children". Cochrane Database of
Systematic Reviews (12): CD004106.
doi:10.1002/14651858.CD004106.pub4. PMID 22161385.
Kew KM, Karner C, Mindus SM, Ferrara G, et al. (Cochrane Airways
Group) (December 2013). "Combination formoterol and budesonide as
maintenance and reliever therapy versus combination inhaler
maintenance for chronic asthma in adults and children". The
Cochrane Database of Systematic Reviews (12): CD009019.
doi:10.1002/14651858.CD009019.pub2. PMID 24343671.
Sobieraj DM, Weeda ER, Nguyen E, Coleman CI, White CM, Lazarus SC,
et al. (April 2018). "Association of Inhaled Corticosteroids and
Long-Acting β-Agonists as Controller and Quick Relief Therapy With
Exacerbations and Symptom Control in Persistent Asthma: A
Systematic Review and Meta-analysis". JAMA. 319 (14): 1485–1496.
doi:10.1001/jama.2018.2769. PMC 5876810. PMID 29554195.
"PACKAGE LEAFLET:INFORMATION FOR THE USER Symbicort® Turbohaler®
200 micrograms/6 micrograms/inhalation, inhalation powder
budesonide, formoterol fumarate dihydrate" (PDF). hpra.ie - Health
Products Regulatory Authority (Irish state agency). July 2015.
Archived (PDF) from the original on 9 August 2018.
Haber G (19 November 2006). "AstraZeneca banking on asthma
inhaler". Delaware News-Journal (delawareonline). Archived from
the original on 30 September 2007. Retrieved 9 July 2020.
"BiResp Spiromax EPAR". European Medicines Agency (EMA). Retrieved
29 April 2020.
"DuoResp Spiromax EPAR". European Medicines Agency (EMA).
Retrieved 29 April 2020.
"Has a generic version of Symbicort been
Budesonide mixture with formoterol". Drug Information
Portal. U.S. National Library of Medicine.
"Budesonide Oral Inhalation". MedlinePlus.
"Formoterol Oral Inhalation". MedlinePlus.
AQUEOUS NEBULIZATION COMPOSITION
Compositions and methods for making and using stable, homogeneous
budesonide compositions are disclosed.
A sterile nebulizer formulation contains formoterol and budesonide
in about 2ml or less of saline and is for treatment of COPD and
asthma and other airways diseases and disorders.
The invention provides a novel method of treating respiratory
diseases, e.g., pediatric asthma, in a continuing regimen with not
more than one daily dose of the drug budesonide using a nebulizer.
( &c... )
RU2203953C2 [ PDF ]
METHOD OF ISOLATION AND PURIFICATION OF BUDESONIDE
FIELD: medicine, pharmacy. SUBSTANCE: invention relates to method
of isolation and purification of budesonide that is highly
effective hormonal broncholytic agent. Isolation of crude
budesonide from cultural fluid is carried out at pH value 2-2.5
and budesonide is extracted from precipitated mixture of steroid
and cultural biomass with ethyl acetate in the ratio budesonide :
ethyl acetate = 1 : (20-28), respectively. Recrystallization of
budesonide is carried out after preliminary soaking crude
budesonide in ethyl acetate in the ratio = 1 : (1.9-2.1),
respectively. Proposed method of isolation and purification of
budesonide allows to obtain budesonide satisfying for all
requirements of pharmacopoeia article, to reduce ethyl acetate
consumption by 8-10 times, to enhance the yield of pharmacopoeia
budesonide by 8-9%. EFFECT: improved method of isolation and
purification of budesonide.
CN102060906A [ PDF ]
Preparation method of R budesonide
The invention relates to the field of medicinal chemistry, in
particular to a preparation method of new R budesonide, which is
characterized in that a budesonide product is synthesized by
carrying out microwave catalytic reaction on the 16-alpha hydroxyl
prednisolone and n-butanal in the presence of a mixed catalyst,
wherein the content of the R budesonide is more than 95 percent.
CN103694306A [ PDF ]
Method for preparing R-isomer by using S-isomer of
The invention discloses a method for preparing an R-isomer by
using an S-isomer of budesonide. The method comprises the steps:
enabling budesonide and acetic anhydride to be subjected to
esterification reaction to obtain budesonide acetate; then,
carrying out oxidative ring cleavage under the action of a strong
oxidant to obtain 16-alpha hydroxyprednisonlone acetate; and
condensing butyraldehyde and the 16-alpha hydroxyprednisonlone
acetate to obtain budesonide acetate, and hydrolyzing to obtain
R-budesonide. The method disclosed by the invention is high in
conversion rate, high in yield and capable of effectively
converting the S-isomer of the budesonide into the
CN110105420A [ PDF ]
Synthesis method of budesonide impurity EP-ZG
The invention provides a synthesis method of a budesonide impurity
EP-ZG. The synthesis method comprises the steps that budesonide
serves as a raw material and is dissolved in an organic solvent,
andthen a metal catalyst is added, so that the budesonide and
hydrogen are subjected to a reduction reaction to generate the
impurity EP-ZG. The synthesis method is simple in process route,
convenient tooperate, good in selectivity and high in yield; the
synthesized budesonide impurity EP-ZG can serve as a reference
substance for detecting and studying the budesonide and be applied
to quality control over the budesonide and preparations related to
the budesonide to control the purity of budesonide active
pharmaceutical ingredients or preparations thereof.
CN102477058A [ PDF ]
New 16,17-dihydroxy intermediate for preparing
A new 16,17-dihydroxy intermediate for preparing budesonide, a
compound shown in formula (I), a method for synthesizing the
compound shown in formula (I) by using a compound shown in formula
(II), and a method for synthesizing budesonide by using the
compound shown in formula (I).
CN110078785A [ PDF ]
Synthesis method of budesonide impurity EP-ZE
The invention provides a synthesis method of a budesonide impurity
EP-ZE. According to the synthesis method, firstly, ZNA-3 is taken
as a raw material and oxidized under the condition of an oxidant
toproduce a compound EP-ZE-IM1; then, the compound EP-ZE-IM1 and
n-butyl aldehyde are subjected to a reaction under the catalysis
action of acid to produce a compound EP-ZE-IM2; finally, the
compound EP-ZE-IM2 is taken as a material and subjected to
hydrolysis under the alkaline condition to produce EP-ZE. The
synthesis method adopts a simple process route and is convenient
to operate, good in selectivity and high in yield; the synthesized
budesonide impurity EP-ZE can serve as a reference substance for
detection and study of budesonide and is applied to quality
control of budesonide and related preparations to control the
purity of raw materials or preparations of budesonide.
CN110078784A [ PDF ]
Synthesis method of budesonide impurity USP-Z1
The invention provides a synthesis method of a budesonide impurity
USP-Z1. According to the synthesis method, firstly, budesonide is
taken as a raw material and subjected to a reaction with butyryl
chloride or butyric anhydride under the condition of an organic
solvent and an acid-binding agent to produce a compound
USP-Z1-IM1; then, the compound USP-Z1-IM1 is dissolved in the
organic solvent, anoxidant is added, oxidation is performed, and
the impurity USP-Z1 is produced. The synthesis method adopts a
simple process route and is convenient to operate, good in
selectivity and high in yield; the synthesized budesonide impurity
USP-Z1 can serve as a reference substance for detection and study
of budesonide and is applied to quality control of budesonide and
related preparations to control the purity of raw materials or
preparations of budesonide.
EP0994119A1 [ PDF ]
Stereoselective process for the preparation of the 22R
epimer of budesonide
The present invention is directed to a stereoselective process for
the preparation of the C-22 R epimer of budesonide, having a
purity higher than 90%, comprising the following steps: a)
stereoselective transketalisation of 9 alpha -bromo-desonide or 9
alpha -iodo-desonide, by reaction with butyraldehyde in the
presence of a halohydric acid selected from between aqueous HBr
and Hl, to give 9 alpha -bromo-budesonide or 9 alpha
-iodo-budesonide; b) treatment of 9 alpha -bromo-budesonide or 9
alpha -iodo-budesonide from step a) with a dehalogenating agent.
CN102477065A [ PDF ]
Novel 16, 17-ketal intermediate for preparing budesonide
The invention provides a novel 16, 17-ketal intermediate for
preparing budesonide and discloses a compound of a formula (III),
a method for synthesizing the compound of the formula (III) by a
compound of a formula (I) and a method for synthesizing budesonide
by the compound of the formula (III).
EP2108653A1 [ PDF ]
Process for preparing budesonide
A process is described for preparing budesonide which comprises
the steps of: a) preparing an aqueous hydrochloric acid solution;
b) reacting 16±-hydroxyprednisolone and butyraldehyde within the
solution prepared in step a), in an inert atmosphere; c) quenching
the reaction of step b) with water. The process of the invention
enables the ratio between the A and B epimers of budesonide to
CN103275168A [ PDF ]
Method for preparing budesonide
The invention belongs to the field of chemical synthesis of
medicaments, and in particular relates to a method for preparing
budesonide. The method comprises the following steps of: selecting
16alpha-hydroxyprednisolone compound as a raw material, performing
a condensation reaction on n-butanal and
16alpha-hydroxyprednisolone at the temperature of between 20 DEG C
below zero and 25 DEG C in a mixed solution of an organic solvent
I and an inorganic acid to obtain a crude budesonide product, and
refining and purifying the crude product to obtain the budesonide
finished product, wherein, the adding ratio of the
16alpha-hydroxyprednisolone to the n-butanal is 20g: (4-12)ml. The
method has the advantages that the condensation reaction condition
is mild, the operation is simply and conveniently carried out, the
yield of the product is high, the high performance liquid
chromatography (HPLC) purity of the crude budesonide product is
high, the ratio of S isomer is high, and the refined finished
product can simultaneously meet the requirements of pharmacopeias
of Europe, America and the like.
CN101279997A [ PDF ]
Novel preparation of budesonide
The invention in particular relates to a new method to prepare
budesonide, belonging to medicinal synthesis. The method
simplifies production process through repeated tests and
experiments, greatly improves yield, reduces prodiction cost and
works out the optimum temperature, time and solvent for the
reaction; the conditions during the reaction are easy to realize;
therefore the method is applicable to large-scale industrial
production to produce budesonide.
CN105061549A [ PDF ]
Budesonide preparing method
The invention discloses a budesonide preparing method. Prednisone
I and acetic anhydride II react to produce
17,21-diacetoxy-1,4-pregnane diene-3,11,20-triketone III, the III
is degreased in an anhydrous solvent to obtain 21-acetoxyl
group-1,4,16-pregnane diene-3,11,20-triketone IV, the IV is
oxidized to obtain
diene-3,11,20-triketone V, the V and n-butyl aldehyde VI are
condensed to obtain 16alpha,17alpha-22(R,S) propyl
diene-3,11,20-triketone VII, the VII is reduced to obtain
diene-3,20-diketone VIII, the VIII is subjected to base catalysis
to obtain budesonide IX. The budesonide preparing method is
suitable for industrial production.
CN107778344A [ PDF ]
Budesonide preparation method
The invention provides a full-novel synthetic route for preparing
budesonide. According to the full-novel synthetic route, utilized
raw materials have lower cost and more easiness in obtaining. The
synthetic route comprises the steps of hydroxylating reaction raw
materials and protecting, then selectively oxidizing five-membered
ring double bonds, bromizing six-membered ring double bonds,
reducingto remove bromine atoms, removing a protecting group and
reacting with n-butanal to obtain a budesonide product. A reaction
process has easiness in operation, yields of all the steps are
higher, obtained products have higher purities, byproduct
generation is effectively avoided, production cost is reduced, and
industrial production is facilitated.
CN103665093A [ PDF ]
Preparation method of (R)-budesonide
The invention relates to a preparation method of adrenocortical
hormone agents, and particularly discloses a preparation method of
[(1-methylethylidene)bis(oxy)]pregna-1,4-diene-3,20-dione is taken
as an initial raw material, and the budesonide (R-isomer) is
obtained through exchange and splitting. The preparation method of
the (R)-budesonide is simple in process, high in yield and
suitable for industrial production.
CN101717428A [ PDF ]
Method for synthesizing budesonide
The invention relates to a method for synthesizing budesonide,
which comprises the following steps of: adding 16 alpha-hydroxy
hydroprednisone shown in a formula (I) and n-butanal into acidic
ionic liquid shown in a formula (II) to perform reaction for 1 to
10 hours at the temperature of between 10 and 100 DEG C; and after
the reaction is finished, performing subsequent treatment on the
reaction liquid to obtain the budesonide shown in a formula (III),
wherein the quantity ratio of the 16 alpha-hydroxy hydroprednisone
to the n-butanal is 1 to 2-5; the mass ratio of the 16
alpha-hydroxy hydroprednisone to the acidic ionic liquid is 1 to
1-10; and in the acidic ionic liquid, R is C1 to C10 alkyl or
substituted alkyl, and the substituent group is sulfonic acid
group or carboxyl, and L is HSO42-, COO-, BF4-, BF6-, AlCl4- or
CF3SO3-. The method for synthesizing the budesonide has the
advantages of easy operation, high capacity, good efficiency,
little three wastes, convenient subsequent treatment and reusable
ionic liquid, which is an economical and practical
CN101863952A [ PDF ]
Preparation method of budesonide
The invention discloses a preparation method of budesonide. The
budesonide is prepared sequentially through the following steps
of: carrying out an esterification reaction on a starting material
and acetic anhydride, wherein the starting material is
prednisolone; carrying out a degreasing reaction in the presence
of a catalyst which can be alkali or an alkali metal salt ;
carrying out an oxidizing reaction with potassium permanganate in
acid environment; carrying out an ester exchange reaction with
alcohol in alkaline environment; carrying out a condensation
reaction with n-butanal, and the like. In the preparation method,
appropriate catalysts are added in the reactions, and reaction
conditions are appropriately controlled so as to achieve the
purposes of increasing the reaction rates inall the steps and
improving the yield of intermediate products, and the product
quality conforms to the standard of the European Pharmacopoeia.
Meanwhile, all the steps have moderate reaction condition and easy
control, low energy consumption, high product yield, small
pollution, easy reaction raw material obtaining and low production
CN107021992A [ PDF ]
Synthetic method for budesonide intermediate, namely,
The invention relates to the field of pharmacy, and discloses a
synthetic method for a budesonide intermediate, namely,
budesonide-17-acetic ester. The synthetic method comprises the
following steps: (1) synthesis of D1: synthesizing 1.0g of D0, 3
to 5mL of THF (Tetrahydrofuran), 0.9 to 1.1mL of triethyl
orthoacetate, 0.007 to 0.009g of p-toluenesulfonic acid
monohydrate, 0.035 to 0.045mL of pyridine, 35 to 45mL of water,
and 0.12 to 0.13g of sodium bicarbonate; (2) synthesis of D2:
synthesizing 1.0g of D1, 7 to 9mL of methanol, 0.60 to 0.64mL of
0.1N hydrochloric acid, 1.50 to 1.58g of 0.1N potassium hydrogen
phthalate, 3.3 to 3.7g of water (A), 15 to 19g of water (B), and 7
to 9g of water (C). The synthetic method has the advantages of low
synthesizing cost, and high process controllability; a prepared
product has high yield and high purity.
CN103724396A [ PDF ]
Preparation method of R-budesonide
The invention discloses a preparation method of an adrenal cortex
hormone medicament and particularly relates to a preparation
method of a high-purity R-budesonide isomer. According to the
method disclosed by the invention, prednisolone is used as an
original raw material and the budesonide acetic ester is prepared
by cyclization, ring opening, esterification, elimination,
oxidation, cyclization and hydrolysis. The method disclosed by the
invention has a simple process and high yield and is suitable for
CN109384827A [ PDF ]
Industrial preparation method for budesonide
The invention relates to an industrial preparation method for
budesonide. Specifically, the method comprises a step of reacting
16alpha-hydroxyprednisolone with n-butyraldehyde in an aqueous
hydrochloric acid solution, dichloromethane and acetonitrile to
prepare budesonid. The method of the invention has the advantages
of industrial implementability, good reproducibility, etc.
WO9211280A1 [ PDF ]
METHOD OF OBTAINING (22R) DIASTEREOISOMER OF BUDESONIDE
By the method according to the invention condensation of 11 beta
,16 alpha ,17 alpha ,21-tetrahydroxy-1,4-pregnadiene-3,20-dione
21-acetate with n-butyric aldehyde is carried out, in the known
way, in the medium of hydrofluoric acid of concentration of 70-80
%. Theisolated crude condensation product is crystallized from
ethanol and obtained 21-acetate of budesonide (22R) of at least 95
% content is hydrolyzed, and the product thus obtained is
crystallized from ethyl acetate.
CN109485689A [ PDF ]
Preparation method of infantile asthma drug budesonide
The invention discloses a preparation method of an infantile
asthma drug budesonide. The method comprises the following step:
carrying out a condensation reaction on a compound I as a raw
material andn-butanal, wherein an acidic ionic liquid is taken as
a catalyst and a solvent during the condensation reaction.
Compared with conventional inorganic catalysts such as
hydrochloric acid, sulfuric acid and perchloric acid, the reaction
yield and the enantio-selectivity can be improved. The
post-treatment is more convenient and simple, too. Meanwhile, a
reaction of hydroxyl on locus 11 and butyraldehyde is avoided to
generate side products as the ketone carboxyl on the locus 11 is
reduced first. After the condensation reaction with butyraldehyde,
unnecessary S configuration can be separated andremoved first by
splitting, so that the follow-up reaction and treatment costs are
saved. The splitting effect of the steps is also relatively ideal.
The preparation method is simple in step, high inyield, high in
enantio-selectivity and low in cost, and is suitable for
industrial production on a large scale.
CN105111273A [ PDF ]
Preparation method of budesonide
The invention discloses a preparation method of budesonide.
The preparation method comprises the following steps: (1) carrying
out n-butyraldehyde aldolization for 16 alpha-hydroxyl
prednisolone acetate as shown in formula (1) to obtain a
budesonide crude prodct; (2) then hydrolyzing 21-acetates; and (3)
collecting the product budesonide from reactant. By adopting the
preparation method, the unstable midbody 16 alpha-hydroxyl
prednisolone is avoided. The preparation method is easy to operate
and control, and the total yield of the budesonide is greatly
increased. The reaction formula is shown in the specification.
PROCESS FOR THE MANUFACTURE OF BUDESONIDE
The present invention relates to a novel process for the
manufacture of (22 R,S)-16.alpha.,
21-dihy-droxypregna-1,4-diene-3,20-dione (I) by reacting 11.beta.,
16.alpha., 17.alpha., 21-tetrahydroxypregna-1,4-diene-3,20-dione
(II) with butanal, CH3CH2CH2CHO in acetonitrile with
p-tolyuenesulphonic acid as a catalyst.