WO2023071994A1 - Utilisation d'un précurseur de nad+ dans la préparation d'un médicament pour le traitement de maladies associées à la sclérose lenticulaire - Google Patents

Utilisation d'un précurseur de nad+ dans la préparation d'un médicament pour le traitement de maladies associées à la sclérose lenticulaire Download PDF

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WO2023071994A1
WO2023071994A1 PCT/CN2022/127077 CN2022127077W WO2023071994A1 WO 2023071994 A1 WO2023071994 A1 WO 2023071994A1 CN 2022127077 W CN2022127077 W CN 2022127077W WO 2023071994 A1 WO2023071994 A1 WO 2023071994A1
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lens
nad
precursor
pharmaceutical composition
administration
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PCT/CN2022/127077
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Chinese (zh)
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刘泉
魏来
冯绮婷
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刘泉
魏来
冯绮婷
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7084—Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0048—Eye, e.g. artificial tears
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/10—Ophthalmic agents for accommodation disorders, e.g. myopia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/12—Ophthalmic agents for cataracts
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0618—Cells of the nervous system
    • C12N5/0621—Eye cells, e.g. cornea, iris pigmented cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2500/30—Organic components
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2500/00—Specific components of cell culture medium
    • C12N2500/30—Organic components
    • C12N2500/32—Amino acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2500/00—Specific components of cell culture medium
    • C12N2500/30—Organic components
    • C12N2500/40—Nucleotides, nucleosides or bases

Definitions

  • the invention relates to the technical field of biomedicine, in particular to the application of an NAD + precursor in the preparation of medicines for treating diseases related to lens sclerosis.
  • Lens sclerosis is a common sign of age-related eye diseases such as presbyopia and senile cataract, but the mechanism of lens sclerosis has not yet been fully elucidated. Many studies have pointed out that the increase in the proportion of water-insoluble protein in the lens protein may be the key factor.
  • Water-insoluble proteins are mainly composed of various post-translationally modified macromolecular proteins. Among them, oxidation modification is the more common one. Oxidized crystallins, especially ⁇ -crystallins, can form disulfide bonds or glycosylation cross-links between molecules and within molecules, leading to abnormal aggregation of proteins and the formation of high molecular weight protein.
  • ⁇ -crystallin is a small molecular chaperone, which can prevent abnormal protein folding and aggregation. Its loss will easily cause other proteins to bind abnormally with the cell membrane and affect the deformation ability of cell tissue. Furthermore, this change will promote the formation of intercellular barriers, resulting in the inability of antioxidant substances to be transported into the nucleus of the lens, and the metabolites in the nucleus cannot be smoothly discharged, which will continuously aggravate the degree of oxidative stress in the lens.
  • Presbyopia is an age-related physiological change in the eye that is closely related to a significant decline in the ability to accommodate within the eye.
  • the Helmholtz adjustment mechanism hypothesis believes that a series of shape changes such as increased thickness, decreased diameter, and increased curvature of the front and rear surfaces caused by the contraction of the ciliary muscle during near vision can enhance the refractive power of the lens and make the object image accurately focused on the retina.
  • the lens gradually hardens and the elasticity of the capsule decreases, resulting in partial or even complete loss of its deformation ability, resulting in a continuous decline in the adjustment range, so that close vision is not enough to meet the daily needs of individuals.
  • Presbyopia manifests as difficulty in near vision and inability to sustain near vision, seriously affecting the quality of life and work of middle-aged and elderly people. Although you can choose to wear glasses or surgical treatment to correct presbyopia, these methods have certain limitations, such as not simple, traumatic, etc., and more importantly, they cannot fundamentally treat presbyopia.
  • Senile cataract is one of the main eye diseases that cause blindness in the world.
  • the clouding and hardening of the lens accompanied by aging is its typical manifestation.
  • Age and environmental exposure are the main risk factors for the onset of senile cataract, which can cause metabolic abnormalities in the lens, and oxidative stress is the currently recognized pathogenesis.
  • Oxidative stress of proteins in the lens will change the morphology of lens fiber cells, destroy their highly ordered structure, and then affect the transparency.
  • oxidative stress may also be the underlying reason for the decrease in the elastic deformation capacity of the lens, and the increase in lens hardness not only further threatens the vision of the middle-aged and elderly people, but also limits the choice of cataract surgery and postoperative visual acuity. quality recovery.
  • many compounds with antioxidant properties have been found to be effective in improving cataract opacity, but their effects on hardness have not yet been studied.
  • Nicotinamide adenine dinucleotide also known as coenzyme I, participates in multiple processes of energy synthesis and metabolism in cells. At the same time, it can also activate a variety of enzymes in the form of coenzyme substrates, and has multiple functions such as anti-oxidative stress and anti-apoptosis.
  • Nicotinamide mononucleotide (nicotinamide mononucleotide, NMN) is the precursor substance of NAD + synthesis, many studies have confirmed that its exogenous supplementation can significantly increase the level of NAD + in the body, and has shown to improve the level of energy metabolism, mitochondrial function and Positive reactions such as oxidative stress. However, there is still no research on the effect of NMN and related compounds on lens hardness (presbyopia, senile cataract).
  • Patent WO 2018052019A1 discloses a visual function improving agent and a visual function improving method, but only generally points out that NMN can improve visual function, and does not mention changing the hardness of the lens, and the usage method and effective usage amount are different from the present application.
  • the first aspect of the present invention provides the application of NAD + precursor in the preparation of medicines for treating diseases related to lens sclerosis, and the medicines are administered locally.
  • the diseases related to lens sclerosis include presbyopia and cataract.
  • the local administration is ocular administration, and more preferably, the local administration includes lens culture in vitro or subconjunctival injection.
  • the drug includes 10-500 mmol/L NAD + precursor.
  • the concentration of the NAD + precursor is 10-40 (eg, 10, 20, 30, 40) mmol/L.
  • the concentration of the NAD + precursor is 500mmol/L.
  • the concentration of the NAD + precursor is 20-50 (eg, 20, 30, 40, 50) mmol/L.
  • the NAD + precursors include tryptophan, niacin, nicotinamide, reduced form of nicotinamide riboside (NRH), nicotinamide mononucleotide (NMN), trigonelline, nicotinamide mononucleotide
  • NAD + precursor is nicotinamide mononucleotide.
  • the medicine also contains other vision-improving ingredients, further preferably, the other vision-improving ingredients include anthocyanins, lutein, docosahexaenoic acid, astaxanthin, lycopene, Taurine, Panthenol, Potassium Aspartate, Chondroitin Sulfate, Zinc, Calcium or Magnesium etc.
  • the other vision-improving ingredients include anthocyanins, lutein, docosahexaenoic acid, astaxanthin, lycopene, Taurine, Panthenol, Potassium Aspartate, Chondroitin Sulfate, Zinc, Calcium or Magnesium etc.
  • the second aspect of the present invention provides a pharmaceutical composition, which includes 10-500mmol/L NAD + precursor, and pharmaceutically acceptable auxiliary materials.
  • the concentration of the NAD + precursor is 10-40 (eg, 10, 20, 30, 40) mmol/L.
  • the concentration of the NAD + precursor is 500mmol/L.
  • the concentration of the NAD + precursor is 20-50 (eg, 20, 30, 40, 50) mmol/L.
  • the NAD + precursors include tryptophan, niacin, nicotinamide, reduced form of nicotinamide riboside (NRH), nicotinamide mononucleotide (NMN), trigonelline, nicotinamide mononucleotide
  • NAD + precursor is nicotinamide mononucleotide.
  • the pharmaceutical composition is administered locally to improve visual function in the pharmaceutical field.
  • the pharmaceutical dosage forms include powder, tablet, sustained-release tablet, chewable tablet, effervescent tablet, lozenge, buccal tablet, sublingual tablet, capsule, fine granule, granule, such as oral preparation, such as pill, dry syrup , solutions, suspensions, syrups and elixirs, as well as eye drops, eye drops, eye ointments, injections, infusions, external preparations, etc.
  • the pharmaceutical composition also includes pharmaceutically acceptable excipients and other pharmaceutically known pharmaceutical additives in the dosage form, which can be properly mixed into the drug according to their physical and chemical properties, biological characteristics, etc. composition.
  • excipients lactose, starch, crystalline cellulose, sodium phosphate, etc.
  • solvents water, soybean oil, physiological saline, non-aqueous solvents for injection, etc.
  • binders starch, gelatin, gum arabic, sodium alginate, Cameron sodium, methylcellulose, ethylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, etc.
  • disintegrants starch, sodium carboxymethylcellulose, etc.
  • lubricants talc, magnesium stearate, calcium stearate, polyethylene glycol, sucrose fatty acid ester, etc.
  • coating agents white sugar, hydroxypropyl cellulose (HPC), shellac, gelatin, glycerin, Hydroxy
  • a method of altering lens hardness comprising the use of NAD + precursors.
  • the method includes using the above-mentioned pharmaceutical composition.
  • the concentration of the NAD + precursor is 10-500 mmol/L.
  • the concentration of the NAD + precursor is 10-40 (eg, 10, 20, 30, 40) mmol/L.
  • the concentration of the NAD + precursor is 500mmol/L.
  • the concentration of the NAD + precursor is 20-50 (eg, 20, 30, 40, 50) mmol/L.
  • the NAD + precursors include tryptophan, niacin, nicotinamide, reduced form of nicotinamide riboside (NRH), nicotinamide mononucleotide (NMN), trigonelline, nicotinamide mononucleotide
  • NAD + precursor is nicotinamide mononucleotide.
  • the method includes topical administration.
  • the method comprises: culturing the lens in NAD + precursor solution in vitro.
  • the culture time is 12 hours.
  • the method comprises: administering NAD + precursor for subconjunctival injection.
  • the injection volume is 5 ⁇ L/time.
  • the fourth aspect of the present invention provides a method for preventing and/or treating eye diseases, the method comprising using NAD + precursor.
  • the concentration of the NAD + precursor is 10-500 mmol/L.
  • the concentration of the NAD + precursor is 10-40 (eg, 10, 20, 30, 40) mmol/L.
  • the concentration of the NAD + precursor is 500mmol/L.
  • the concentration of the NAD + precursor is 20-50 (eg, 20, 30, 40, 50) mmol/L.
  • the NAD + precursors include tryptophan, niacin, nicotinamide, reduced form of nicotinamide riboside (NRH), nicotinamide mononucleotide (NMN), trigonelline, nicotinamide mononucleotide
  • NAD + precursor is nicotinamide mononucleotide.
  • the eye diseases include presbyopia and cataract.
  • the method comprises: culturing the lens in NAD + precursor solution in vitro.
  • the culture time is 12 hours.
  • the method comprises: administering NAD + precursor for subconjunctival injection.
  • the injection volume is 5 ⁇ L/time.
  • the subject of the agent for changing the hardness of the lens, the food composition, and the pharmaceutical composition of the present invention can be mammals, such as humans, monkeys, dogs, rabbits, mice, and rats.
  • treating means slowing, interrupting, arresting, controlling, stopping, alleviating, or reversing the progression or severity of a sign, symptom, disorder, condition, or disease after the disease has begun to develop, but not necessarily The complete elimination of all disease-related signs, symptoms, conditions, or disorders is contemplated.
  • the NAD + precursor in the present invention acts directly on the eye through local administration at a specific concentration, which can effectively increase the axial strain of the aging lens, improve the hardness of the lens, and partially restore elasticity. Therefore, the compound can restore the adjustment ability and treat presbyopia and senile cataract by regulating the hardness of the lens.
  • Figure 1 Changes in lens hardness in vitro, where * is P ⁇ 0.05, ** is P ⁇ 0.01;
  • Figure 2 Changes in lens hardness in vivo experiments (subconjunctival injection), where * is P ⁇ 0.05;
  • Figure 3 Changes in the degree of lens opacity in senile cataract in vitro; the arrows indicate ring-shaped cataracts;
  • Figure 4 Changes in lens hardness of senile cataract in vitro; where * is P ⁇ 0.05;
  • Figure 5 Changes in lens hardness in vivo experiments (gastric administration).
  • mice Eight-month-old mice (C57BL/6J) were randomly divided into control and treatment groups, and the lenses were incubated in complete MEM medium (containing 10% fetal bovine serum and 1% penicillin/streptomycin) for 2 hours to recover metabolic activity. Subsequently, the medium in the treatment group was replaced with serum-free MEM medium containing different concentrations (10-40mmol/L, specifically 10, 20, 30, 40mmol/L) of nicotinamide mononucleotide solution, and the control group was only serum-free MEM medium and incubate for 12 hours at 37°C in a 5% CO 2 incubator. After 12 hours, wash the lens 3 times with light buffer of HBSS solution. Lens elasticity was measured using the known coverslip indentation method.
  • the specific operation is: in the acrylic square vessel containing 65-70mL HBSS solution, the lens is stably fixed in the special small hole in the vessel in the axial direction, and the rectangular prism at a certain position from the lens can reflect the overall outline of the lens.
  • the lens was deformed by the weight of the cover glass, and the deformation was counted to evaluate the hardness.
  • mice Eight-month-old mice (C57BL/6J) were randomly divided into a control group and a treatment group. After the mice were anesthetized by intraperitoneal injection of pentobarbital sodium, the conjunctiva of the right eye was fully exposed.
  • Nicotinamide mononucleotide solution improves lens turbidity and hardness in senile cataract mice
  • mice 14-month-old C57BL/6J mice were selected and randomly divided into control group and treatment group. After the materials were collected, a stereomicroscope (SteREO Discovery V8 stereomicroscope, Zeiss, Germany) was used to record the opacity degree of the mouse lens under sterile conditions to ensure the successful preparation of the senile cataract mouse model. The lenses were incubated for 2 hours in complete MEM medium (containing 10% fetal calf serum and 1% penicillin/streptomycin) to restore metabolic activity.
  • complete MEM medium containing 10% fetal calf serum and 1% penicillin/streptomycin
  • the medium in the treatment group was replaced with serum-free MEM medium containing different concentrations (20-50mmol/L, specifically 20, 30, 40, 50mmol/L) of nicotinamide mononucleotide solution, and the control group was only serum-free MEM medium and incubate for 12 hours at 37°C in a 5% CO 2 incubator. After 12 hours, wash the lens 3 times with light buffer of HBSS solution. Lens opacity was recorded again using a stereomicroscope prior to hardness testing. Lens hardness was then measured using the coverslip indentation method described above.
  • Example 3 Nicotinamide mononucleotide solution gavage administration method has a general effect on improving the hardness of the lens of mice
  • mice Eight-month-old C57BL/6J mice were randomly divided into control group and treatment group. After the mouse is weighed, hold the mouse with the left hand so that its head, neck and body are in a straight line, use a 1mL syringe and a No. 8 gavage needle, enter the gavage needle from the corner of the mouse's mouth, touch the palate and push it inward gently , after entering the stomach, inject the drug solution at 100mg/kg/day, once a day, for 1 month. One month after gavage, the eyeballs were removed to obtain the lens, and the hardness of the lens was measured by the above-mentioned cover glass indentation method.
  • nicotinamide mononucleotide solution can enhance the adjustment ability and treat presbyopia and senile cataract by increasing the axial strain of the lens, improving the hardness of the lens, and reducing the opacity of the lens in cataract. .

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Abstract

L'invention concerne l'utilisation d'un précurseur de NAD+ dans la préparation d'un médicament pour le traitement de maladies associées à la sclérose lenticulaire. En particulier, la concentration en précurseur de NAD+ est de 10 à 500 mmoles/l et une lentille ex vivo est cultivée dans une solution de précurseur de NAD+ à l'aide d'un moyen d'administration locale ou la solution de précurseur de NAD+ est utilisée pour une injection sous-conjonctivale, de manière à traiter des maladies associées à la sclérose lenticulaire, ce qui présente une valeur importante pour la préparation de médicaments dans le traitement de maladies associées à la sclérose lenticulaire.
PCT/CN2022/127077 2021-10-27 2022-10-24 Utilisation d'un précurseur de nad+ dans la préparation d'un médicament pour le traitement de maladies associées à la sclérose lenticulaire WO2023071994A1 (fr)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2071316C1 (ru) * 1993-08-05 1997-01-10 Болдырев Александр Александрович Глазные капли для лечения катаракты
US20020025311A1 (en) * 2000-08-16 2002-02-28 Till Jonathan S. Presbyopia treatment by lens alteration
US20080139990A1 (en) * 2000-08-16 2008-06-12 Encore Health, Llc Presbyopia Treatment by Lens Alteration
CN110496215A (zh) * 2019-08-23 2019-11-26 中国人民解放军总医院 一种治疗老视的水性滴眼液及其制备方法

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2071316C1 (ru) * 1993-08-05 1997-01-10 Болдырев Александр Александрович Глазные капли для лечения катаракты
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