CN106474121B - A kind of medicine for treating chronic pelvic inflammatory disease - Google Patents
A kind of medicine for treating chronic pelvic inflammatory disease Download PDFInfo
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- CN106474121B CN106474121B CN201611055679.XA CN201611055679A CN106474121B CN 106474121 B CN106474121 B CN 106474121B CN 201611055679 A CN201611055679 A CN 201611055679A CN 106474121 B CN106474121 B CN 106474121B
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- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical class C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluic acid Chemical class CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 229940096978 oral tablet Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 210000003101 oviduct Anatomy 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 210000004303 peritoneum Anatomy 0.000 description 1
- 108010049224 perlecan Proteins 0.000 description 1
- IPBVNPXQWQGGJP-UHFFFAOYSA-N phenyl acetate Chemical class CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 229940023488 pill Drugs 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 238000004094 preconcentration Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000003405 preventing effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- ULWHHBHJGPPBCO-UHFFFAOYSA-N propane-1,1-diol Chemical class CCC(O)O ULWHHBHJGPPBCO-UHFFFAOYSA-N 0.000 description 1
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical class CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- UORVCLMRJXCDCP-UHFFFAOYSA-M propynoate Chemical compound [O-]C(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-M 0.000 description 1
- 239000001944 prunus armeniaca kernel oil Substances 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229940116351 sebacate Drugs 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 235000021391 short chain fatty acids Nutrition 0.000 description 1
- 150000004666 short chain fatty acids Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000012109 statistical procedure Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical compound [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229940071104 xylenesulfonate Drugs 0.000 description 1
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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention relates to a kind of medicine for treating chronic pelvic inflammatory disease, the medicine includes the compound and pharmaceutically acceptable carrier with structural formula described herein of effective dose, wherein R1 independently selected from：F, Cl, Br or I；R2 independently selected from：H, the C optionally replaced by halogen, hydroxyl, alkoxy, alkoxy carbonyl, amino1‑6Alkyl；R3 independently selected from：H, the C optionally replaced by halogen, hydroxyl, alkoxy, alkoxy carbonyl, amino1‑6Alkyl.The degree of inflammation in uterus caused by the medicine of the present invention can mitigate chronic pelvic inflammatory disease.
Description
Technical field
The present invention relates to field of medicaments, specifically, the present invention relates to a kind of medicine for treating chronic pelvic inflammatory disease.
Background technology
Chronic pelvic inflammatory disease refers to female internal genital organs and its surrounding connective tissue, the chronic inflammation of pelvic peritoneum.Its is main
Clinical manifestation is paramenia, leucorrhea increasing, waist abdomen pain and infertile etc., has such as formed chronic appendages inflammation, then accessible lump.
Symptom is visible：1) chronic pelvic pain：The cicatricial adhesion of chronic inflammation formation and pelvic congestion, often cause lower abdomen falling inflation, pain
Pain and lumbosacral region are ached.Often aggravate after tired, sexual intercourse and before and after menstruation.2) infertile and ectopic pregnancy：Fallopian tube adhesion blocks
Infertile and ectopic pregnancy can be caused.Infertile incidence is 20%~30% after acute pelvitis of pelvic cavity.3) menoxenia：Endometritis is normal
There is irregular menses；Pelvic congestion can cause menorrhagia；Ovarian function can cause menstrual disorder when damaging.4) constitutional symptom：More not
Substantially, only low-heat sometimes, it is susceptible tired.Because course of disease time is longer, some patientss may occur in which neurasthenia symptom, such as spirit
The depressed, whole body is uncomfortable, have a sleepless night etc..When patient's resistance is poor, acute or subacute breaking-out is tended to have.Sign, if endometrium
Inflammation, uterus increase, tenderness；If salpingitis, then the thickening fallopian tubal in rope strip is contacted in uterus one or both sides, and have
Mild tenderness.If hydrosalpinx or tubo-ovarian cyst, then Cystic lesions are touched in pelvic cavity one or both sides, activity is more
It is limited.If during connective tissue inflammation of pelvic cavity, uterus is in often retroversioflexion, limitation of activity or adhesion are fixed, uterus one or both sides
There is sheet to thicken, tenderness, the normal thickening of uterosacral ligament, be hardened, there is tenderness.Chronic pelvic inflammatory disease is common gynecological disease.In China,
Due to the limitation of personal hygiene condition and medical condition, or the sterile working idea in gynaecology's minor operation and family planning operation
Indifferent, the incidence of disease of chronic pelvic inflammatory disease is very high.
The content of the invention
It is an object of the invention to provide a kind of medicine for treating chronic pelvic inflammatory disease.
In order to realize the purpose of the present invention, the present invention provides a kind of medicine for treating chronic pelvic inflammatory disease, and the medicine is included
Effective dose have following structural compound and pharmaceutically acceptable carrier：
Wherein
R1 independently selected from：F, Cl, Br or I；
R2 independently selected from：H, the C optionally replaced by halogen, hydroxyl, alkoxy, alkoxy carbonyl, amino1-6Alkyl；
R3 independently selected from：H, the C optionally replaced by halogen, hydroxyl, alkoxy, alkoxy carbonyl, amino1-6Alkyl.
Preferably, R1 is Br.
Preferably, R2 is H.
Preferably, R3 is H.
The present invention also provides a kind of method for treating chronic pelvic inflammatory disease, and methods described includes the object to this kind for the treatment of of needs
Give the medicine or its pharmaceutically acceptable salt any one of the claim 1-4 of effective dose.
The present invention also provides purposes of the compound with following structural in the medicine for preparing treatment chronic pelvic inflammatory disease：
Wherein
R1 independently selected from：F, Cl, Br or I；
R2 independently selected from：H, the C optionally replaced by halogen, hydroxyl, alkoxy, alkoxy carbonyl, amino1-6Alkyl；
R3 independently selected from：H, the C optionally replaced by halogen, hydroxyl, alkoxy, alkoxy carbonyl, amino1-6Alkyl.
Preferably, R1 is Br.
Preferably, R2 is H.
Preferably, R3 is H.
Before further describing the invention, it should be appreciated that the invention is not restricted to described embodiment, because they
Certainly may change.It should also be understood that the purpose of terms used herein is only description embodiment, it is not used to be construed as limiting,
Because the scope of the present invention is only limited by the appended claims.
Unless otherwise indicated, all scientific and technical terminologies used herein are understood with one skilled in the art of the present invention
Usual implication it is identical.All reference is incorporated into full for all patents referred to herein, application, published application and other publications
Herein.If it is opposite that definition listed in this paper patent, application and other publications is included in definition in the part with reference
Or it is inconsistent, the definition in the part, which will be overwhelmed, quotes the definition for including this paper.
Indicated herein with the singulative " one " used in appended claims, " one kind " and " described " plural number that includes
Thing, unless the context.It should also be noted that claims can be formulated as excluding any optional key element.Equally,
This explanation application is made to quote claim element relatively using this kind of removing property term, such as " only having ", " only ", or make
With the antecedent basis of " negative " limitation.
Terms used herein "comprising", " containing " and " comprising " are used with its opening, infinite implication.
To provide before conciser description, some quantitative expressions herein without using term " about ".It should be understood that either
No clearly to use term " about ", each content herein represents actual given numerical value, and it is also represented by being based on ability
The approximation for the given numerical value that domain ordinary skill can rationally infer, including due to experiment and/or measuring condition produce it is this kind of
The equivalent value and approximation of given numerical value.No matter when as a percentage during yield, this kind of yield is represented in specific chemistry
The entity quality that metering is used to calculate yield than under the conditions of can be obtained the maximum amount of ratio with same entity.Percents
Concentration represent quality ratio, unless otherwise indicated.
Unless otherwise indicated, all scientific and technical terminologies used herein are understood with one skilled in the art of the present invention
Usual implication it is identical.Although can also use and implement or test this hair with similar or equivalent any method described herein and material
It is bright, but preferred method and material are described below.All publications being mentioned above are totally incorporated herein by reference, and cited
Publication, which is associated, comes these methods of disclosure and description and/or material.
Unless otherwise indicated, the methods and techniques of embodiment of the present invention typically follow conventional method well known in the art and entered
Row and as some or bibliography particularly described in, the bibliography through this specification reference and discussion.
See, e.g., Loudon, OrganicChemistry (《Organic chemistry》), fourth edition；New York：Oxford University Press
(OxfordUniversityPress), 2002,360-361,1084-1085 page；Smith and March, March '
sAdvancedOrganicChemistry：Reactions, Mechanisms, andStructure (《Numb chi is senior to organise
Learn：Reaction, mechanism and structure》), the 5th edition, Wei Li scientific companies (Wiley-Interscience), 2001.
It is used to name the nomenclature of the motif compound explanation in the embodiments herein herein.The nomenclature typically uses city
Available AutoNom softwares (the MDL companies of Andrew in California is holy) are sold, version 12.0.2 is obtained.
It should be understood that for clarity, some features of the invention described in the content of single each embodiment are also
It may be incorporated in single embodiment and provide.Conversely, in the content of single embodiment Short Description it is of the invention
Each feature can also be provided separately or be provided in the form of any suitable sub-portfolio.With the chemical base represented by changeable-shaped
All combinations of the related embodiment of group are specific to be included in the scope of the invention and by being disclosed herein, just as herein individually and
Clearly disclose each combined with each down to such combination and include compound (that is, separable, table certainly as stable compound
The compound for detection biological activity of seeking peace).In addition, chemical group listed in describing the embodiment of such changeable-shaped
All sub-portfolios are also specifically included in the scope of the invention and by being disclosed herein, just as disclosing individually and clearly chemical base herein
Each and each such sub-portfolio of group.
" pharmaceutically acceptable salt " is intended to indicate that the free acid of compound illustrated herein or the salt of alkali, its do not have toxicity,
It can biologically tolerate or biologically be suitable to be administered to object.Generally referring to, S.M.Berge etc.,
“PharmaceuticalSalts(《Pharmaceutical salts》) " J.Pharm.Sci., 1977,66,1-19.It is preferred that it is pharmaceutically acceptable
Salt be pharmaceutically effectively and be adapted for contact with object tissue without excessive toxicity, stimulate or it is anaphylactoid those.Herein
Described compound can have group acid enough, the enough group of alkalescence, two kinds of functional group or each more than a kind of
Type, and therefore with a variety of inorganic or organic base, and inorganic and organic acid reaction to form pharmaceutically acceptable salt.
The example of pharmaceutically acceptable salt includes sulfate, pyrosulfate, disulfate, sulphite, bisulfite
Salt, phosphate, dibasic alkaliine, dihydric phosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, acetic acid
Salt, propionate, caprate, caprylate, acrylates, formates, isobutyrate, caproate, enanthate, propiolate, oxalic acid
Salt, malonate, succinate, suberate, sebacate, fumarate, maleate, Isosorbide-5-Nitrae-acetylenedicarboxylic acid salt, 1,6-
Hexyndioic acid salt, benzoate, chloro benzoate, methyl benzoic acid salt, dinitro-benzoate, hydroxy benzoate, methoxy
Yl benzoic acid salt, phthalate, sulfonate, metilsulfate, propyl sulfonic acid salt, benzene sulfonate, xylenesulfonate,
Naphthalene -1- sulfonate, naphthalene-2-sulfonic acid salt, phenyl acetate salt, phenylpropionic acid salt, PB, citrate, lactate, γ -
Hydroxybutyric acid salt, glycollate, tartrate and mandelate.The list of other suitable pharmaceutically acceptable salts is found in
Remington′sPharmaceuticalSciences(《Remington pharmaceutical science》), the 17th edition, Easton, PA
Mack Publishing Company (MackPublishingCompany), 1985.
For therapeutic purposes, including compound described herein pharmaceutical composition may also include one or more can pharmaceutically connect
The excipient received.Pharmaceutically acceptable excipient refers to without toxicity and is biologically suitable to the material being administered to object.It is this kind of
Excipient promotes the administration process of compound described herein and compatible with active component.The example of pharmaceutically acceptable excipient
Including stabilizer, lubricant, surfactant, diluent, antioxidant, binding agent, colouring agent, swelling agent, emulsifying agent or tune
Taste agent.In a preferred embodiment, the pharmaceutical composition of the invention is aseptic composite.It can be used known to those skilled in the art
Or the complex technique that can be used prepares pharmaceutical composition.
The present invention also relates to aseptic composite, including meet the country for determining said composition and the composition of local code.
According to conventional method prepared by a variety of formulations is used in this area, pharmaceutical composition and compound described herein can match somebody with somebody
Be made as solution, emulsion, supensoid agent or dispersant in appropriate drug solvent or supporting agent, or pill, tablet, lozenge, suppository,
Wafer, sugar-coat agent, granule, powder agent, the powder agent for reconstruction or the capsule together with solid carriers.The medicine of the present invention
Composition can be given by appropriate route of delivery, such as oral, parenteral, rectum, intranasal, part or through eye approach, or lead to
Cross suction.Preferably, said composition is formulated as being used for administered intravenously or orally.
For being administered orally, compound of the invention can (such as tablet or capsule) or solution, emulsion in solid form
Or the form of supensoid agent is provided.To prepare Orally administered composition, the compound of the present invention can be prepared to form such as daily about 0.01
To about 50mg/kg or daily about 0.05 to about 20mg/kg or daily about 0.1 to about 10mg/kg dosage.Other dosage include
Daily about 0.1mg to 1g, daily about 1mg to about 10mg, daily about 10mg to about 50mg, daily about 50mg to about 250mg or every
Its about 250mg to 1g.Oral tablet may include and compatible pharmaceutically acceptable excipient (such as diluent, disintegrant, bonding
Agent, lubricant, sweetener, flavor enhancement, colouring agent and preservative) mixing active component.Suitable inert filler includes carbonic acid
Sodium and calcium carbonate, sodium phosphate and calcium phosphate, lactose, starch, sugar, glucose, methylcellulose, magnesium stearate, mannitol, sorb
Sugar alcohol etc..Exemplary fluids oral vehicle includes ethanol, glycerine, water etc..Starch, polyvinylpyrrolidone (PVP), starch second
Alkyd sodium, microcrystalline cellulose and alginic acid are exemplary disintegrants.Bonding agent may include starch and gelatin.If it does, lubrication
Agent can be magnesium stearate, stearic acid or talcum.It is possible if desired to use certain material (such as glycerin monostearate or two
Tristerin) coating tablet is with the absorption in delaying stomach and intestine road, or use enteric coating peridium.
Capsule for oral administration includes hard and Perle.To prepare hard gelatin capsule, can by active component with
Solid, semisolid or liquid diluent mixing.Perle can be by by active component and water, oil (such as peanut oil or olive
Olive oil), atoleine, the mixture of the list of short chain fatty acids and two glyceride, the mode of polyethylene glycol 400 or mixed with propylene glycol
Prepare.
Liquid for oral administration can be the form of supensoid agent, solution, emulsion or syrup, or can face
The dry products rebuild with preceding use water or other suitable supporting agents.This kind of fluid composition is optional to be included：It is pharmaceutically acceptable to assign
Shape agent, such as suspending agent (for example D-sorbite, methylcellulose, mosanom, gelatin, hydroxyethyl cellulose, carboxymethyl cellulose,
Aluminium stearate gel etc.)；Non-aqueous supporting agent, such as oily (such as apricot kernel oil or fractionated coconut oil), propane diols, ethanol or water；It is anti-
Rotten agent (such as methyl p-hydroxybenzoate or propylparaben or sorbic acid)；Wetting agent (such as lecithin)；And (such as
Fruit needs) flavor enhancement or colouring agent.
The composition of the present invention, which can be formulated as suppository, is used for rectally.(including intravenous, muscle is used for parenteral
Interior, intraperitoneal, intranasal or subcutaneous route), reagent of the invention can be buffered to suitable pH with aseptic aqueous solution agent or supensoid agent
There is provided with isotonicity or in parenteral acceptable oily form.Suitable aqueous carrier includes Ringer's solution and isotonic
Sodium chloride.This kind of form can be that unit dosage form (such as ampoule or disposable injection device), multiple dose form (such as can be from
The middle medicine bottle for taking out suitable dose) or solid form or available for the pre-concentration liquid for preparing injectable formulation.At several minutes to number
In it time, the scope of exemplary infusion dosage is about 1 to the 1000 μ reagents mixed with drug-carrier of g/kg/ minutes.
For intranasal, suction or oral administration, the spray agent for for example also including suitable carrier can be used to give this hair
Bright pharmaceutical composition.
Used for local, the compound of the present invention is preferably formulated as emulsifiable paste or ointment or the class suitable for local administration
Like supporting agent.For local administration, the compound of the present invention can be mixed with drug-carrier, concentration is the pact that medicine accounts for supporting agent
0.1% to about 10%.Another pattern for giving the reagent of the present invention is to reach the effect of transdermal delivery using patch formulation.
Terms used herein " treatment " or " processing " include " preventative " and " therapeutic " treatment." preventative " treatment, which refers to, to be pushed away
Symptom or reduction disease or symptom development or recurrence that slow disease, the development of disease symptomses or medical conditions, suppression are likely to occur
Risk." therapeutic " treatment includes reduction existing disease, the order of severity of symptom or illness or suppresses its deterioration.Therefore, control
Treat the essence system for including improving or prevent the deterioration of existing disease symptomses, prevent other symptoms, improve or prevent symptom
Unite reason, suppress imbalance or disease, for example prevent imbalance or advancing of disease, mitigate imbalance or disease, promote imbalance or disease
Regression, mitigation disease or illness caused by imbalance stop disease or the symptom of imbalance.
Term " object ", which refers to, needs the mammalian subject of the treatment, such as people.
In the treatment method according to the present invention, " effective dose ", which refers to needed for the object for being enough to make this kind for the treatment of of needs is obtained, to be controlled
Treat the amount or dosage of benefit.The present invention compound effective dose or dosage can by conventional method (as modeling, dosage escalation or
Clinical test) determine, wherein considering conventional factors, for example the pattern or approach of administration or medicine delivery, the medicine of reagent are for power
The judgement of the order of severity and process, the health status of object, the state of an illness and body weight and the doctor in charge that learn, infect.Exemplary dose
The scope of amount is daily per Kilogram subject body weight about 1ug to 2mg active agent, preferably from about 0.05 to 100mg/kg/ days or about 1
To 35mg/kg/ days or about 0.1 to 10mg/kg/ days.In other embodiments, the scope of exemplary dose is about 1mg to about
1g/ days, or about 1-500,1-250,1-100,1-50,50-500 or 250-500mg/ days.Accumulated dose can be with single or separated
Dosage device (such as BID, TID, QID) is given.
Once the disease of patient improves, you can regulating dosage is used for preventative or maintaining treatment.For example, the agent of administration
Amount or frequency or both can change to be down to symptom keeps the required level for treating or preventing effect.Certainly, if symptom
Mitigate to proper level, treatment can be stopped.But during any symptom recurrence, patient can require that the interval in long-term basis is controlled
Treat.Patient may also need to the long-term treatment on the basis of long time-histories.
Retouched by reference to specific embodiment with the schematic synthetic schemes of general preparative methods in this article and afterwards
State Exemplary chemical entity useful in the method for the present invention.Those skilled in the art will appreciate that to obtain herein many
Compound is planted, parent material can suitably be selected, so that the reaction scheme protected by suitably with or without makes
With final required substituent with the product needed for generating.Or, it may be necessary to or want in final required substituting group position
Upper use can pass through the proper group that reaction scheme is carried and can substituted in due course by required substituent.In addition, this area skill
The order that art personnel should be understood that the conversion shown in following scheme and arbitrarily can hold with specific side base function phase is carried out.It is general
Each reaction described in scheme is preferably carried out under about 0 DEG C of reflux temperature to organic solvent used.All material generally may be used
Bought at market supply business.
The degree of inflammation in uterus caused by the medicine of the present invention can mitigate chronic pelvic inflammatory disease.
Brief description of the drawings
Fig. 1 is that phenol paste causes rat chronic pelvic infecton model pathological section (× 100), wherein A：Normal group；B：
Model control group；C：Positive controls；D、E、F：The high, medium and low dosage group of medicine of the present invention.
Embodiment
Below by way of the description of embodiment, the invention will be further described, but this is not the limit to the present invention
System, those skilled in the art are according to the basic thought of the present invention, and various modifications may be made or improves, but without departing from this
The basic thought of invention, within the scope of the present invention.
Experimental example
The structural formula of medical compounds of the present invention is：
Take female sd inbred rats, 190~230g of weight.Rat is anaesthetized through yellow Jackets (30mg/kg, i.p.), the back of the body
Position is fixed on operating table, after belly routine disinfection, median incision of lower abdomen about 2cm exposures uterus, with No. 4 syringe needles respectively in uterus
The careful inserting needle of crotch, compound each 0.075mL of phenol paste is slowly injected into ovary direction, and note is finished, and abdomen is closed in layering, sterilizes art
Area.Modeling terminates.
If Normal group, model control group, positive controls (JINJI KELI, purchased from the limited public affairs of Hang Seng of Zhongshan city medicine company
Department) and the high, medium and low dosage group of medicine of the present invention, every group 10, wherein Normal group does not carry out modeling.It is grouped within postoperative 2nd day
Administration, positive controls dosage is daily 12.5g raw medicinal herbs/kg, is made into suspension oral gavage with distilled water before use, continuously
Gavage 14d.0.01g the compounds of this invention plus 2000mL normal salines are taken into suspension, high, normal, basic dose of medicine of the present invention
Amount group distinguishes daily gavage 10mL/100g, 5mL/100g, 2.5mL/100g, continuous gavage 14d.Normal group and model pair
Distilled water is given according to a group gavage, administered volume is 2mL/100g, continuous gavage 14d.Animal is put to death within 15th day, rat is taken out in separation
Uterus, after weighing, puts 10% formalin by uterus and fixes, and makes paraffin section, and histology microscopy is made in HE dyeing.
Standards of grading
Cavity wall structure：Each clear layer is "-"；Proper mucous membrane gland structure is disorderly unclear or disappears for "+"；Muscle layer with
Unclear mucous layer boundary is " ++ "；Unclear holostrome structure is " +++ ".
Epithelial cell：Simple columnar is "-"；Cell is flat or downright bad come off less than 1/3 of epithelial cell is "+"；More than 1/3
For " ++ "；It is " +++ " that necrosis, which disappears, completely.
Inner membrance congestion and edema：It is "-" without congestion and edema；The slight congestion and edema of lamina propria is "+"；Obvious congestion and edema for "+
+”；Muscle layer even placenta percreta has congestion and edema to be " +++ ".
Chronic cell infiltration：Lymphocyte, thick liquid cell in 10 × 20 times of lower 4 unit areas of number of micrometer grid
Number, takes its average.Each layer has no that inflammatory cell is "-"；It is largely "+" only to be seen in proper mucous membrane；Also visible, the quantity in muscle layer
20~30 are " ++ "；Holostrome all has, quantity be more than 30 for " +++
Fibroblast：It is "-" without hyperplasia；It is "+" on a small quantity that proper mucous membrane, which has,；Muscle layer also has, and amount is relatively generally " ++ "；Entirely
Layer all has, and it is " +++ " that quantity, which is more than 30,.
Uterine cavity size：Uterine cavity reduces or degrees of expansion person within 1/3 is slight lesion, and more than 1/3 to 2/3 is moderate
Lesion, is moderate lesion more than 2/3.
Every kind of lesion degree from light to heavy labeled as+, ++, +++, ++++, no lesion person be "-", respectively scoring for 1 point, 2
Point, 3 points, 4 points, 0 point.Add up all fractions, calculates dividing equally for every group of animalThe higher prompting inflammatory disorderses of score value
Degree is more serious.
Statistical procedures
Statistical analysis is carried out with the softwares of SPSS 17.0.Data are with mean ± standard deviationRepresent, many group differences
Using variance analysis, two groups of group differences are examined with Dunnett-t.P<0.05 represents that difference is statistically significant.
Pathology results
See Fig. 1.Phenol paste causes rat chronic pelvic infecton model result to show：Model group metrosynizesis, diminish, it is a small number of
Case uterine cavity is expanded, endometrium lamina propria fibroblast proliferation, and produces collagenic connective tissue, causes palace wall fibr tissue to increase
It is raw, hence it is evident that person's part palace wall normal configuration disappears, and is that the fiber of collagenzation is substituted.Positive drug and medicine of the present invention can mitigate chronic
The degree of inflammation in uterus caused by pelvic infecton, show as endometrial epithelium denaturation, muscle layer congestion and edema and cell infiltration and
Lamina propria, basic unit's inflammatory reaction mitigate.
Medicine Pyrogentisinic Acid paste of the present invention causes the influence of the scorching change degree of rat uterus see the table below.
Compare with Normal group, * P<0.05, represent modeling success；Compare with model control group,ΔP<0.05, represent effect
Fruit has significant difference；Compare with positive controls,&P<0.05, represent that effect has significant difference.
Claims (1)
1. the compound with following structural prepare endometrial epithelium denaturation, muscle layer congestion and edema and cell infiltration with
And the purposes in lamina propria, the medicine of basic unit's inflammatory reaction mitigation：
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| CN201611055679.XA CN106474121B (en) | 2016-11-25 | 2016-11-25 | A kind of medicine for treating chronic pelvic inflammatory disease |
| CN201710973021.5A CN107625767A (en) | 2016-11-25 | 2016-11-25 | A kind of medicine for treating chronic pelvic inflammatory disease |
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