CN114870016A - Microemulsion foaming agent of JAK inhibitor and application thereof - Google Patents
Microemulsion foaming agent of JAK inhibitor and application thereof Download PDFInfo
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- 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
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- 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
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
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- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
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- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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- A61K9/10—Dispersions; Emulsions
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- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/12—Aerosols; Foams
- A61K9/122—Foams; Dry foams
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention relates to a composition of microemulsion foaming agent for treating alopecia areata, atopic dermatitis and vitiligo and a preparation method thereof. Has effects of moistening skin and keeping moisture, has no irritation to skin, no side effects such as itch, burning sensation and pricking sensation, and has no related dermatosis symptom after stopping administration.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and relates to a JAK inhibitor microemulsion foaming agent, a preparation method and application thereof.
Background
The JAK inhibitor can selectively inhibit JAK kinase and block a JAK/STAT signal channel, and is mainly used for screening therapeutic drugs for diseases of a blood system, tumors, rheumatoid arthritis, psoriasis and the like clinically. Janus kinases (JAKs) are a family of intracellular non-receptor tyrosine kinases that transduce cytokine-mediated signals through the JAK-STAT pathway. Since members of the type I and type II cytokine receptor families do not possess catalytic kinase activity, they rely on the JAK tyrosine kinase family to phosphorylate and activate downstream proteins involved in their signal transduction pathways. The receptor exists as a counterpart polypeptide and thus exhibits two intracellular signaling domains. JAKs are associated with a proline-rich region in each intracellular domain that is adjacent to the cell membrane, called the box1/box2 region. Upon binding of the receptor to its respective cytokine/ligand, it undergoes a conformational change that brings the two JAKs close enough to phosphorylate each other. JAK autophosphorylation induces its own conformational changes that enable it to transduce intracellular signals by further phosphorylating and activating transcription factors called STATs. Activated STATs dissociate from receptors and form dimers before they migrate to the nucleus, where they regulate transcription of selected genes. JAK inhibitors include Abutinib, Upatinib, Lactaritinib, Baritinib, tofacitinib, SHR0302, Jackstinib hydrochloride, and the like.
Luccotinib, a small molecule, is an orally available specific inhibitor of Janus kinase subtypes 1 and 2(JAK1 and JAK2) and was approved in the united states for the treatment of high risk myelofibrosis in 2011. Subsequently, indications have expanded to include polycythemia vera, which is resistant or intolerant to conventional therapies, and acute graft versus host disease, which is resistant to corticosteroids.
Aboxitinib is a once daily oral JAK1 inhibitor and is also one of the members of the global pipeline of the Perey JAK inhibitor, and acts by regulating a variety of cytokines associated with atopic dermatitis including interleukins IL-4, IL-13, IL-31, IL-22, and Thymic Stromal Lymphopoietin (TSLP). Inhibition of JAK1 is thought to modulate a variety of cytokines involved in the pathophysiology of atopic dermatitis, including interleukins IL-4, IL-13, IL-31, IL-22 and Thymic Stromal Lymphopoietin (TSLP) for 9 months 2021, which was approved by the british pharmaceutical and health care administration (MHRA) for the treatment of moderate to severe Atopic Dermatitis (AD) in adults and adolescents 12 years and older. This is the first time that abacitinib is approved by drug administration worldwide. Subsequently, the ambuxinib tablet was approved for marketing in japan, korea, the european union, and the united states in succession. In addition, pfurre has also studied the drug for various indications such as psoriasis, systemic lupus erythematosus and arthritis. Currently only tablet dosage forms are available.
Lucentin cream with OPZELURA, FDA approved for the inc CORP on 21/9/2021, is marketed and approved for short-term and non-continuous chronic treatment of mild to moderate AD in non-immunocompromised patients 12 years and older. AD is a chronic skin disorder affecting people over 2100 million 12 years of age and older in the united states and characterized by inflammation and itching, signs and symptoms including irritated and itchy skin, which results in red lesions that may exude and scab, and patients are more susceptible to bacterial, viral and fungal infections. The Rukutinib cream can also be used for treating atopic dermatitis and vitiligo.
Compared with the cream, the microemulsion foaming agent has the advantages that the skin retention amount of the cream is small, the microemulsion foaming agent can bring the defect of greasy feeling to a patient, the microemulsion foaming agent has good stability, spreadability and easiness in smearing, is particularly suitable for hairy skin, is easier to use and does not adhere to the hair, has larger skin penetration and skin retention amount than soft cream, can provide the patient with the feeling of non-greasiness after being used, does not pollute clothes, and is simple and convenient in clinical use. Therefore, there is a need to develop a novel JAK inhibitor microemulsion foaming agent.
Disclosure of Invention
The invention aims to overcome the defects of the JAK inhibitor cream and provides a micro-emulsion foaming agent of a JAK inhibitor, a preparation method and application thereof.
The purpose of the invention is realized by the following technical scheme:
the invention relates to a micro-emulsion foaming agent of a JAK inhibitor, which is characterized by consisting of an effective treatment amount of the JAK inhibitor and auxiliary materials, wherein the auxiliary materials comprise an oil-in-water surfactant (foaming type), an auxiliary surfactant, an oil phase, a humectant or solvent, an emollient, a chelating agent and a preservative.
As an embodiment, the present invention relates to a microemulsion foaming agent of JAK inhibitor, wherein the active ingredient of JAK inhibitor is a therapeutically effective amount of JAK inhibitor, preferably 0.5% to 3% of JAK inhibitor active ingredient selected from any one or more of ambuxinib, upatinib, ructinib, barrettinib, tofacitinib, SHR0302, morroniib, and jack-tinib hydrochloride.
The JAK inhibitor microemulsion foaming agent is a solution type or suspension type oil-in-water preparation, and comprises 2-25% of oil-in-water surfactant, preferably 15-25%, and 1-10% of cosurfactant, preferably 2-8%. 0.2-1%, preferably 0.5-0.9%, oil-containing phase 0.01-1%, preferably 0.5-0.8%, humectant or solvent 4-25%, preferably 5-20%, emollient 0.5-2%, preferably 0.5-1%, preservative 0.1-1.0%, preferably 0.2-0.9%.
As an embodiment, the ratio of oil-in-water surfactant to co-surfactant is 6: 1 to 3: 1.
the oil-in-water surfactant is selected from one or more of caprylic/capric polyethylene glycol glyceride, cetearyl alcohol polyoxyethylene ether-20 and lauryl alcohol polyoxyethylene ether, preferably one or two of caprylic/capric polyethylene glycol glyceride and cetearyl alcohol polyoxyethylene ether-20.
A co-surfactant is a surfactant that acts by further reducing the interfacial energy in addition to a surfactant, but does not function effectively as a surfactant alone. The cosurfactant is selected from one or more of polyglycerin fatty acid ester, propylene glycol fatty acid ester, glyceryl monostearate, diethylene glycol monoethyl ether, polyglycerin 3-oleate, etc., preferably one or two of polyglycerin fatty acid ester, propylene glycol fatty acid ester, and diethylene glycol monoethyl ether.
The oil phase is selected from medium chain triglyceride, cyclomethicone, isopropyl palmitate, glyceryl triacetate light liquid paraffin, etc., preferably any one or more of medium chain triglyceride, cyclomethicone and isopropyl palmitate.
The chelate is selected from one of disodium edetate and calcium sodium edetate, preferably disodium edetate.
The humectant or solvent is selected from one or more of propylene glycol, glycerol, polyethylene glycol-200, etc., preferably one or two of propylene glycol and polyethylene glycol-200.
The emollient is selected from one or more of propylene glycol dinonyl ester, polydimethylsiloxane 350, and polyethylene glycol-7-cocoglyceride, preferably one or two of propylene glycol dinonyl ester and polydimethylsiloxane 350.
The antiseptic is one or more of phenoxyethanol, propyl p-hydroxybenzoate, methyl p-hydroxybenzoate, ethyl p-hydroxybenzoate, etc., preferably phenoxyethanol, propyl p-hydroxybenzoate, and methyl p-hydroxybenzoate.
As one embodiment, the invention relates to a JAK inhibitor microemulsion foaming agent, which comprises the following raw materials and formula (in mass percentage based on the total weight of the JAK inhibitor microemulsion foaming agent):
the invention also relates to a preparation method of the micro-emulsion foaming agent of the JAK inhibitor, which comprises the following steps:
(1) preparing an active phase, dissolving the active ingredients in a prescription amount in a humectant or a solvent at 30-80 ℃, adding a cosurfactant, and cooling to room temperature.
(2) Preparing an oil phase: stirring and dissolving the O/W emulsifier, the oil phase, the chelating agent, the preservative and the emollient with the prescribed amount at the temperature of 30-80 ℃, and cooling to room temperature.
(3) Adding the active phase into the oil phase, and stirring uniformly.
(4) And (3) adding the mixture into water at room temperature, uniformly stirring, and adjusting the pH value by using hydrochloric acid/sodium hydroxide to obtain the micro-emulsion foaming agent.
The invention also relates to application of the micro-emulsion foaming agent of the JAK inhibitor in external application medicines for treating alopecia areata, atopic dermatitis, vitiligo and the like.
Compared with the prior art, the invention has the following beneficial effects:
microemulsion foams, i.e., microemulsion foams, compositions containing JAK inhibitors, without boosters, spontaneously form oil-in-water microemulsions when aqueous phase/oil-in-water surfactant/co-surfactant, oil phase, humectant or solvent, emollient, chelating agent, preservative are mixed together at appropriate concentrations. The microemulsions formed are transparent to opalescent, optically isotropic and thermodynamically stable. The microemulsion can improve drug solubility, reduce skin irritation, maintain the concentration difference between internal phase and external phase of drug, and promote drug to continuously penetrate stratum corneum. The microemulsion foaming agent can spray foam without a boosting agent by passing the microemulsion through a specific drug delivery device, has good spreadability, is easy to smear, has good patient compliance, and is more convenient and has higher skin retention and permeation especially for the use of skin containing hair.
Drawings
Other features, objects and advantages of the invention will become more apparent upon reading of the detailed description of non-limiting embodiments with reference to the following drawings:
FIG. 1 example 1 foaming of a microemulsion foaming agent;
FIG. 2 example 2 foaming of a microemulsion foaming agent;
FIG. 3 example 3 foaming of a microemulsion foaming agent;
FIG. 4 example 4 foaming of a microemulsion foaming agent;
FIG. 5 example 5 foaming of microemulsion foaming agent
FIG. 6 is a graph showing the foaming of the microemulsion foaming agent of comparative example 2.
Detailed Description
The present invention will be described in detail with reference to examples. The following examples will assist those skilled in the art in further understanding the invention, but are not intended to limit the invention in any way. It should be noted that it would be apparent to those skilled in the art that several modifications and improvements can be made without departing from the inventive concept. All falling within the scope of the present invention.
The preparation method of the microemulsion foaming agent of the JAK inhibitor comprises the following steps:
(1) preparation of active phase: dissolving the active ingredients in the prescription amount in a solvent propylene glycol, adding a cosurfactant, stirring and dissolving at 30-50 ℃, and cooling to room temperature.
(2) Preparation of oil phase: stirring O/W emulsifier, oil phase, chelating agent, antiseptic, and emollient, heating to 30-50 deg.C, dissolving, mixing, and cooling to room temperature.
(3) And adding the mixed oil phase into the water phase, uniformly stirring, and regulating the pH to 2.8-5.0 by using hydrochloric acid/sodium hydroxide to obtain the micro-emulsion foaming agent.
Specific application examples are as follows:
examples 1 to 4
The embodiments 1 to 4 relate to a preparation method of an iridocortib microemulsion foaming agent, and the raw and auxiliary materials comprise the following components in percentage by weight:
TABLE 1
Example 5
The embodiment relates to preparation of an Abuxitinib micro-emulsion foaming agent.
A microemulsion foaming agent containing 1% of Abuxitinib was prepared according to the formulation of Table 2 and the preparation methods of examples 1 to 4.
TABLE 2
| Example 5 | |
| Name (R) | Ratio of |
| Aboxitinib | 1 |
| Caprylic capric acid polyethylene glycol glyceride | 20 |
| Polyglyceryl fatty acid ester | 4 |
| Medium chain triglycerides | 0.5 |
| Polydimethylsiloxane 350 | 0.5 |
| Propylene glycol | 22 |
| EDTA-2Na | 0.05 |
| Phenoxyethanol | 0.5 |
| P-hydroxybenzoic acid methyl ester | 0.1 |
| Propyl p-hydroxybenzoate | 0.05 |
| Hydrochloric acid/sodium hydroxide | Proper amount of |
| Water (W) | 51.3 |
| Qs | 100 |
Comparative example 1 preparation of control formulation
The preparation of the rukuranib-containing cream was carried out as a control preparation according to the formulation in table 5, paragraph 0274, page 19 of the CN105853356A patent specification, and the preparation process in paragraph 0277-0286. The raw materials and the auxiliary materials account for the following table 3.
TABLE 3
Comparative example 2
The comparative example relates to the preparation of an iridocotinib microemulsion foaming agent, the raw materials and the auxiliary materials account for the following table 4, the preparation method is the same as that of example 2, but the adopted surfactant is different.
TABLE 4
| Name (R) | Ratio of | Function of auxiliary material |
| Lucotinib phosphate | 1.98 | API |
| Tween 60 | 20 | o/w surfactants |
| Polyglyceryl fatty acid ester | 4 | Cosurfactant |
| Medium chain triglycerides | 0.5 | Oil phase |
| Polydimethylsiloxane 350 | 0.5 | Skin-moistening agent |
| Propylene glycol | 15 | Humectant and solvent |
| EDTA-2Na | 0.05 | Chelating agents |
| Phenoxyethanol | 0.5 | Preservative |
| P-hydroxybenzoic acid methyl ester | 0.1 | Preservative agent |
| Propyl p-hydroxybenzoate | 0.05 | Preservative |
| Hydrochloric acid/sodium hydroxide | Proper amount of | pH regulator |
| Water (W) | 57.32 | Solvent(s) |
| Qs | 100 |
Example 6 quality comparison study
The viscosity, centrifugation, properties, emulsion droplet size, pH, content, related substances and content uniformity measurements were performed on examples 1-5 and comparative examples 1-2, and the results are shown in Table 5 below.
TABLE 5
And (4) conclusion: the foaming conditions of the tinib microemulsion foaming agents prepared in examples 1-5 and comparative example 2 are shown in attached figures 1-6. The microemulsion foaming agents prepared according to examples 1 to 5 have good foaming ability, and the microemulsion foaming agent prepared according to comparative example 2 has poor foaming ability, and is easy to become a solution without being uniformly coated in clinical use, so that the microemulsion flows or drips from the surface of the skin.
The preparation of the lucentitinib microemulsion foaming agent according to the patent examples 1-4 and the preparation of the Abuxitinib microemulsion foaming agent according to the example 5 have good stability and spreadability, are easy to apply, especially aiming at the skin with hair, are easier to use and do not adhere to the hair compared with the cream in the comparative example 1.
Example 7 Long term stability comparative study results
Samples prepared in examples 1-4 and comparative examples 1 and 2 were placed at 30 + -2 deg.C and RH 60% + -5% humidity, and sampled for detection of properties, viscosity, pH, content, and related substances at 1 month and 3 months, respectively, and the specific detection results are shown in Table 6 below.
TABLE 6
From the long-term stability comparison data of example 7, it can be seen that the microemulsion foaming agents prepared in examples 1 to 5 have good stability, and the properties, viscosity, pH value, content and related substance indexes have no significant changes in a long-term three-month period. It is demonstrated that the microemulsion foams prepared according to examples 1-5 substantially meet the stability requirements during use.
Example 8 comparative in vitro transdermal test study:
1) the method comprises the following steps: franz diffusion cell method;
2) the instrument comprises: LOGAN 918-12 system as long-distance medicine transdermal diffusion tester
3) Skin: the experimental pigskin has the thickness of 0.8-1mm and the contact diameter of 2 cm;
4) receiving liquid: physiological saline;
5) the temperature of the received liquid: 32 plus or minus 0.5 ℃;
6) rotating speed: 600 rpm;
7) sample preparation: the preparation with different prescriptions is respectively and uniformly coated on experimental pigskin, the sample size of each preparation is about 200mg, and the pigskin without cream is used as blank pigskin.
8) Volume of the diffusion cell: 12 ml;
9) the sampling mode is as follows: all samples are taken;
10) sampling time points are as follows: 2h, 4h, 6h, 10h, 21h and 24 h;
11) sample analysis: the results of LC/MS measurement are shown in Table 7.
TABLE 7
As can be seen from the in vitro transdermal test of example 8, the available micro-emulsion foams of the rutenib prepared in examples 1 to 4 have larger skin penetration and skin retention than the soft cream, and the in vitro penetration test shows that the micro-emulsion foams have better clinical effect than comparative example 1 and comparative example 2. The microemulsion foaming agent is an oil-in-water microemulsion foaming agent, and can provide a non-greasy feeling to a patient after use, and does not soil clothes. The clinical use is simple and convenient.
The foregoing description of specific embodiments of the present invention has been presented. It is to be understood that the present invention is not limited to the specific embodiments described above, and that various changes and modifications may be made by one skilled in the art within the scope of the appended claims without departing from the spirit of the invention.
Claims (10)
1. The microemulsion foaming agent of the JAK inhibitor is characterized by consisting of an active ingredient of the JAK inhibitor and auxiliary materials, wherein the auxiliary materials comprise an oil-in-water surfactant, an auxiliary surfactant, an oil phase, a humectant or a solvent, an emollient, a chelating agent and a preservative.
2. The microemulsion foaming agent of the JAK inhibitor according to claim 1, wherein the JAK inhibitor is selected from one or more of the group consisting of ruckerib phosphate, ruckerib, ambuxinib and molutinib, and the active ingredient of the JAK inhibitor accounts for 0.5-3% by mass.
3. The microemulsion foaming agent of the JAK inhibitor according to claim 1, wherein the auxiliary materials comprise, by mass percent, 2-25% of oil-in-water surfactant, 1-10% of cosurfactant, 0.2-1% of oil-containing phase, 0.01-1% of chelating agent, 4-25% of humectant or solvent, 0.5-2% of emollient, and 0.1-1.0% of preservative, based on the total weight of the microemulsion foaming agent of the JAK inhibitor.
4. The microemulsion foaming agent of JAK inhibitor according to claim 3, wherein the excipients comprise, by mass, 15-25% of oil-in-water surfactant, 2-8% of cosurfactant, 0.5-0.9% of oil-containing phase, 0.5-0.8% of chelating agent, 5-20% of humectant or solvent, 0.5-1% of emollient, and 0.2-0.9% of preservative.
5. The JAK inhibitor microemulsion foaming agent according to any one of claims 2 or 4, wherein the active ingredients and the auxiliary materials of the JAK inhibitor are as follows in percentage by mass based on the total weight of the JAK inhibitor microemulsion foaming agent: 0.5-3% of reed cotinib phosphate or reed cotinib or ambuxinib or molocitinib, 15-25% of caprylic capric acid polyethylene glycol glyceride, 2-8% of polyglycerol fatty acid ester or propylene glycol fatty acid ester, 0.5-0.9% of medium chain triglyceride, 0.5-1% of polydimethylsiloxane 350, 5-20% of propylene glycol, 0.5-0.8% of EDTA-2Na, 0.2-0.8% of phenoxyethanol, 0.05-0.15% of methyl p-hydroxybenzoate, 0.01-0.1% of propyl p-hydroxybenzoate, a proper amount of hydrochloric acid or sodium hydroxide and water with fixed weight of 100.
6. The microemulsion foaming agent of the JAK inhibitor according to claim 1, wherein the oil-in-water surfactant is any one of caprylic capric polyethylene glycol glyceride, cetearyl alcohol polyoxyethylene ether-20, lauryl alcohol polyoxyethylene ether; the cosurfactant is one or more of polyglyceryl fatty acid ester, propylene glycol fatty acid ester, glyceryl monostearate, diethylene glycol monoethyl ether and polyglyceryl 3-oleate.
7. A microemulsion foaming agent for a JAK inhibitor according to claim 7, having a ratio of oil-in-water surfactant to co-surfactant of 6: 1 to 3: 1.
8. the microemulsion foaming agent of a JAK inhibitor according to claim 1, wherein the oil phase is selected from any one of medium chain triglycerides, cyclomethicone, isopropyl palmitate, glyceryl triacetate light liquid paraffin,
the humectant or the solvent is any one of propylene glycol, glycerol and polyethylene glycol-200,
the emollient is selected from any one of propylene glycol dinonyl ester, polydimethylsiloxane 350 and polyethylene glycol-7 cocoglyceride.
9. A process for preparing a microemulsion foaming agent of a JAK inhibitor as claimed in claim 1, comprising the steps of:
a, preparing an active phase: dissolving the active ingredients in the prescription amount in a humectant or a solvent at the temperature of 30-80 ℃, adding a cosurfactant, and cooling to room temperature;
b, oil phase preparation: stirring and dissolving the O/W emulsifier, the oil phase, the chelating agent, the preservative and the emollient with the prescribed amount at the temperature of 30-80 ℃, and cooling to room temperature;
c, adding the active phase into the oil phase, and uniformly stirring;
and d, adding the oil phase containing the active phase into water at room temperature, uniformly stirring, and adjusting the pH value to obtain the microemulsion foaming agent.
10. The microemulsion foaming agent of a JAK inhibitor according to claim 1, for use as an external preparation for treating alopecia areata, atopic dermatitis, vitiligo, etc.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
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| CN202210423007.9A CN114870016B (en) | 2022-04-21 | 2022-04-21 | Micro-emulsion foaming agent of JAK inhibitor and application thereof |
| PCT/CN2023/089004 WO2023202580A1 (en) | 2022-04-21 | 2023-04-18 | Microemulsion foam of jak inhibitor and use thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN202210423007.9A CN114870016B (en) | 2022-04-21 | 2022-04-21 | Micro-emulsion foaming agent of JAK inhibitor and application thereof |
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| CN114870016A true CN114870016A (en) | 2022-08-09 |
| CN114870016B CN114870016B (en) | 2023-05-26 |
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| WO (1) | WO2023202580A1 (en) |
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| WO2023114832A1 (en) * | 2021-12-15 | 2023-06-22 | Arcutis Biotherapeutics, Inc. | Stable formulations of shr0302 |
| WO2023202580A1 (en) * | 2022-04-21 | 2023-10-26 | 上海博悦生物科技有限公司 | Microemulsion foam of jak inhibitor and use thereof |
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| Publication number | Publication date |
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| CN114870016B (en) | 2023-05-26 |
| WO2023202580A1 (en) | 2023-10-26 |
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